Current Issues in Molecular Biology

2024

Jump to: 2023, 2022, 2021

17 pages, 4000 KiB

Open AccessArticle

Protective Effects of Cervus elaphus and Eucommia ulmoides Mixture (KGC01CE) on Muscle Loss and Function in Aged Rats

by Gi-Bang Koo, Han Ol Kwon, Jong Han Kim, Seung Ho Lee, Sung Lye Shim and Kyoung Hwa Jang

Curr. Issues Mol. Biol. 2024, 46(10), 11190-11206; https://doi.org/10.3390/cimb46100664 - 4 Oct 2024

Viewed by 1009

Abstract

Sarcopenia is a condition characterized by a progressive loss of muscle mass and function which are influenced by certain factors such as aging, nutritional deficiencies, and chronic diseases. Despite numerous efforts to prevent or treat sarcopenia, effective therapeutic options for this disease remain [...] Read more.

Sarcopenia is a condition characterized by a progressive loss of muscle mass and function which are influenced by certain factors such as aging, nutritional deficiencies, and chronic diseases. Despite numerous efforts to prevent or treat sarcopenia, effective therapeutic options for this disease remain limited. This study aims to evaluate the effects of KGC01CE treatment, a mixture of Cervus elaphus (Ce) and Eucommia ulmoides (Eu), which are well-known traditional herbal medicines in Asia, on age-related muscle loss and functional decline in aged rats. KGC01CE has been found to be more effective than the individual extracts in inhibiting dexamethasone (DEX)-induced muscle atrophy and improving muscle mass and grip strength in C2C12 cells and aged rats. Moreover, animal studies were conducted to determine the minimum effective dose, and a 12-week oral administration of KGC01CE treatment at doses of 50, 100, and 200 mg/kg to 15-month-old aged rats resulted in a dose-dependent increase in lean mass, muscle mass, grip strength, and muscle cross-sectional area (CSA), which had decreased due to aging. Furthermore, it was shown that KGC01CE activated the phosphatidylinositol 3-kinase (PI3K)/Akt pathway and inhibited the expression of muscle-degrading proteins MuRF, Atrogin-1, and myostatin. These results suggest that KGC01CE treatment may effectively prevent muscle loss and functional decline, providing a novel therapeutic strategy for sarcopenia. Full article

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12 pages, 6890 KiB

Open AccessArticle

Engineering of Substrate-Binding Domain to Improve Catalytic Activity of Chondroitin B Lyase with Semi-Rational Design

by Miao Tian, Yuan-Yuan Xu, Yang-Nan Li, Shen Yu, Yi-Lin Wang, Xiao-Lai Ma and Ye-Wang Zhang

Curr. Issues Mol. Biol. 2024, 46(9), 9916-9927; https://doi.org/10.3390/cimb46090591 - 6 Sep 2024

Cited by 1 | Viewed by 713

Abstract

Dermatan sulfate and chondroitin sulfate are dietary supplements that can be utilized as prophylactics against thrombus formation. Low-molecular-weight dermatan sulfate (LMWDS) is particularly advantageous due to its high absorbability. The enzymatic synthesis of low-molecular-weight dermatan sulfates (LMWDSs) using chondroitin B lyase is a [...] Read more.

Dermatan sulfate and chondroitin sulfate are dietary supplements that can be utilized as prophylactics against thrombus formation. Low-molecular-weight dermatan sulfate (LMWDS) is particularly advantageous due to its high absorbability. The enzymatic synthesis of low-molecular-weight dermatan sulfates (LMWDSs) using chondroitin B lyase is a sustainable and environmentally friendly approach to manufacturing. However, the industrial application of chondroitin B lyases is severely hampered by their low catalytic activity. To improve the activity, a semi-rational design strategy of engineering the substrate-binding domain of chondroitin B lyase was performed based on the structure. The binding domain was subjected to screening of critical residues for modification using multiple sequence alignments and molecular docking. A total of thirteen single-point mutants were constructed and analyzed to assess their catalytic characteristics. Out of these, S90T, N103C, H134Y, and R159K exhibited noteworthy enhancements in activity. This study also examined combinatorial mutagenesis and found that the mutant H134Y/R159K exhibited a substantially enhanced catalytic activity of 1266.74 U/mg, which was 3.21-fold that of the wild-type one. Molecular docking revealed that the enhanced activity of the mutant could be attributed to the formation of new hydrogen bonds and hydrophobic interactions with the substrate as well as neighbor residues. The highly active mutant would benefit the utilization of chondroitin B lyase in pharmaceuticals and functional foods. Full article

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14 pages, 3201 KiB

Open AccessArticle

Endothelin-3 Suppresses Luteinizing Hormone Receptor Expression by Regulating the cAMP-PKA Pathway in Hen Granulosa Cells

by Yurong Tai, Deping Han, Xue Yang, Ganxian Cai, Huaiyu Li, Junying Li and Xuemei Deng

Curr. Issues Mol. Biol. 2024, 46(8), 7832-7845; https://doi.org/10.3390/cimb46080464 - 23 Jul 2024

Viewed by 844

Abstract

Previous research identified the expression of EDN3 in granulosa cells of preovulatory follicles in chickens. Notably, the expression level of EDN3 in Silky Fowl with low egg-laying performance was significantly higher than that in high-yield laying breed White Leghorn. Given the crucial role [...] Read more.

Previous research identified the expression of EDN3 in granulosa cells of preovulatory follicles in chickens. Notably, the expression level of EDN3 in Silky Fowl with low egg-laying performance was significantly higher than that in high-yield laying breed White Leghorn. Given the crucial role of granulosa cells in follicular development and maturation, it is very important to study the effect of EDN3 on the biological function of granular cells. In this study, an EDN3 overexpression plasmid was constructed and transfected into granular cells. The viability of these cells was detected using quantiative (qPCR), Cell Counting Kit-8 (CCK8), and 5-Ethynyl-2′-deoxyuridine (EdU) assays. Gonadal hormone synthesis was detected using enzyme-linked immunosorbent assay (ELISA) techniques. Finally, transcriptome sequencing was employed to identify differentially expressed genes. Result showed thatoverexpression of EDN3 was observed to promote cell viability. In addition, it significantly inhibits the expressions of LHR and cAMP-PKA signaling pathways. Cell transcriptome sequencing data displayed that EDN3 can upregulate energy metabolism and immune-related signaling pathways, whereas follicle maturation and the GnRH signaling pathway were downregulated. In conclusion, this study demonstrates that EDN3 can enhance granulosa cell viability and inhibit the expression of LHCGR, a process likely mediated through the cAMP-PKA signaling pathway. However, further evidence is required to substantiate the regulatory relationship between EDN3 and the cAMP-PKA signaling pathway. Full article

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31 pages, 2020 KiB

Open AccessReview

Beyond the Coagulation Cascade: Vitamin K and Its Multifaceted Impact on Human and Domesticated Animal Health

by Rebecka A. Sadler, Anna K. Shoveller, Umesh K. Shandilya, Armen Charchoglyan, Lauraine Wagter-Lesperance, Byram W. Bridle, Bonnie A. Mallard and Niel A. Karrow

Curr. Issues Mol. Biol. 2024, 46(7), 7001-7031; https://doi.org/10.3390/cimb46070418 - 4 Jul 2024

Cited by 1 | Viewed by 2039

Abstract

Vitamin K (VK) is an essential micronutrient impacting many systems in the body. This lipid-soluble vitamin is found in various plant and animal products and is absorbed via the lymphatic system. This biomolecule’s importance to human health includes but is not limited to [...] Read more.

Vitamin K (VK) is an essential micronutrient impacting many systems in the body. This lipid-soluble vitamin is found in various plant and animal products and is absorbed via the lymphatic system. This biomolecule’s importance to human health includes but is not limited to its promotion of brain, cardiovascular, bone, and immune functions. These biological properties are also necessary for maintaining domesticated animal health. The synergistic impact of both VK and vitamin D (VD) maximizes these health benefits, specifically for the circulatory and skeletal systems. This manuscript reviews VK’s properties, molecular structures, nutrikinetics, mechanisms of action, daily requirements, safety in supplemental form, biomarkers used for its detection, and impacts on various organs. The purpose of synthesizing this information is to evaluate the potential uses of VK for the treatment or prevention of diseases. Full article

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1 pages, 154 KiB

Open AccessRetraction

RETRACTED: Al-Salmi, F.A.; Hamza, R.Z. Efficacy of Vanadyl Sulfate and Selenium Tetrachloride as Anti-Diabetic Agents against Hyperglycemia and Oxidative Stress Induced by Diabetes Mellitus in Male Rats. Curr. Issues Mol. Biol. 2022, 44, 94–104

by Fawziah A. Al-Salmi and Reham Z. Hamza

Curr. Issues Mol. Biol. 2024, 46(6), 5550; https://doi.org/10.3390/cimb46060331 - 31 May 2024

Viewed by 587

Abstract

Current Issues in Molecular Biology Editorial Office retracts the article titled “Efficacy of Vanadyl Sulfate and Selenium Tetrachloride as Anti-Diabetic Agents against Hyperglycemia and Oxidative Stress Induced by Diabetes Mellitus in Male Rats” [...] Full article

11 pages, 1337 KiB

Open AccessArticle

Study on Chemical Composition and Biological Activity of Psidium guajava Leaf Extracts

by Hyonam Park, Bohee Kim, Yuri Kang and Woonjung Kim

Curr. Issues Mol. Biol. 2024, 46(3), 2133-2143; https://doi.org/10.3390/cimb46030137 - 6 Mar 2024

Viewed by 6050

Abstract

Guava (Psidium guajava) is a plant widely distributed in tropical and subtropical regions. Its leaves contain a large amount of physiological molecules such as flavonoid, sesquiterpene, triterpenoid, coumarin, alkaloid, and tannin molecules with antioxidative and anti-inflammatory effects. In this study, the [...] Read more.

Guava (Psidium guajava) is a plant widely distributed in tropical and subtropical regions. Its leaves contain a large amount of physiological molecules such as flavonoid, sesquiterpene, triterpenoid, coumarin, alkaloid, and tannin molecules with antioxidative and anti-inflammatory effects. In this study, the use of concentrated P. guajava leaf extract molecules as a functional natural material was evaluated by confirming the extract’s antioxidative, antibacterial, tyrosinase activity inhibition, and collagenase activity inhibition effects and its trans-2-nonenal removal ability. As a result of the analysis of the antioxidant and antibacterial components of concentrated P. guajava leaf extract molecules through GC-MS, a large amount of aromatic hydrocarbon molecules were detected. When different concentrations of ethanol were used for extraction, the leaf extract concentrated with 70% ethanol showed the most effective active molecules. As a result of measuring DPPH radical scavenging activity, a concentration-dependent antioxidant activity was confirmed. The antioxidant activity tended to increase when the ethanol content used for extraction was increased. Molecules such as 2,4-di-tert-butylphenol, caryophyllene oxide, and γ-muurolene in P. guajava leaf extract concentrate appeared to have antibacterial activities against S. aureus bacteria known to cause atopy. As ethanol content increased, the inhibitory effect on tyrosinase activity was increased. In addition, when ethanol content was 50%, the concentrated leaf extract was able to remove trans-2-nonenal by 52.4%. As a result of determining the concentrated leaf extract’s collagenase inhibition activity, an inhibition rate close to that of ascorbic acid, a positive control, was confirmed. The concentrated guajava leaf extract molecules were confirmed to have whitening and wrinkle-improving functionality. Thus, the P. guajava leaf extract has high potential as a food and natural cosmetic material. Full article

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13 pages, 3320 KiB

Open AccessArticle

Antidiabetic Effect of Urolithin A in Cultured L6 Myotubes and Type 2 Diabetic Model KK-A^y/Ta Mice with Glucose Intolerance

by Shinji Kondo, Shin-ichi Adachi, Wataru Komatsu, Fumiaki Yoshizawa and Kazumi Yagasaki

Curr. Issues Mol. Biol. 2024, 46(2), 1078-1090; https://doi.org/10.3390/cimb46020068 - 24 Jan 2024

Cited by 2 | Viewed by 2058

Abstract

Diabetes is caused by abnormal glucose metabolism, and muscle, the largest tissue in the human body, is largely involved. Urolithin A (UroA) is a major intestinal and microbial metabolite of ellagic acid and ellagitannins and is found in fruits such as strawberry and [...] Read more.

Diabetes is caused by abnormal glucose metabolism, and muscle, the largest tissue in the human body, is largely involved. Urolithin A (UroA) is a major intestinal and microbial metabolite of ellagic acid and ellagitannins and is found in fruits such as strawberry and pomegranate. In this present study, we investigated the antidiabetic effects of UroA in L6 myotubes and in KK-A^y/Ta, a mouse model of type 2 diabetes (T2D). UroA treatment elevated the glucose uptake (GU) of L6 myotubes in the absence of insulin. This elevation in GU by UroA treatment was partially inhibited by the concurrent addition of LY294002, an inhibitor of phosphatidylinositol 3-kinase (PI3K) which activates Akt (PKB: protein kinase B) or Compound C, an inhibitor of 5′-adenosine monophosphate-activated protein kinase (AMPK). Moreover, UroA was found to activate both pathways of Akt and AMPK, and then to promote translocation of glucose transporter 4 (GLUT4) from the cytosol to the plasma membrane in L6 myotubes. Based on these in vitro findings, an intraperitoneal glucose tolerance test (IPGTT) was performed after the oral administration of UroA for 3 weeks to KK-A^y/Ta mice with glucose intolerance. UroA was demonstrated to alleviate glucose intolerance. These results suggest that UroA is a biofactor with antihyperglycemic effects in the T2D state. Full article

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2023

Jump to: 2024, 2022, 2021

14 pages, 2629 KiB

Open AccessArticle

Water Extract of Portulaca Oleracea Inhibits PEDV Infection-Induced Pyrolysis by Caspase-1/GSDMD

by Yu Zhang, Yueyue Liu, Shifa Yang, Bin Yin, Zengcheng Zhao, Zhongli Huang, Jiaqiang Wu, Shuqian Lin and Xin Wang

Curr. Issues Mol. Biol. 2023, 45(12), 10211-10224; https://doi.org/10.3390/cimb45120637 - 18 Dec 2023

Cited by 2 | Viewed by 1636

Abstract

Porcine epidemic diarrhea virus (PEDV) belongs to the coronavirus family and the coronavirus genus, causing contact enteric infection in pigs. It is one of the most serious diseases that threatens the pig industry. However, there is currently no specific drug to prevent and [...] Read more.

Porcine epidemic diarrhea virus (PEDV) belongs to the coronavirus family and the coronavirus genus, causing contact enteric infection in pigs. It is one of the most serious diseases that threatens the pig industry. However, there is currently no specific drug to prevent and treat the disease, indicating that we need to be vigilant about the spread of the disease and the development of anti-PEDV drugs. The dried aerial parts of the plant Portulaca oleracea in the family Portulacaceous, whose decoction can be used to treat acute enteritis, dysentery, diarrhea, and other diseases. This study explored the potential mechanism of water extract of Portulaca oleracea (WEPO) in PEDV-induced pyroptosis in Vero cells. PEDV decreased the viability of Vero cells in a dose- and time-dependent manner, causing cell damage, upregulating the level of intracellular Nlrp3, and inhibiting the level of Gasdermin D (GSDMD) and the activation of Caspase-1. WEPO can inhibit PEDV-induced pyroptosis, reduce the elevation of inflammatory factors caused by infection, and exhibit a dose-dependent effect. Knockdown of Caspase-1 and GSDMD separately can induce the production of the inflammatory factor IL-1β to significantly decrease and increase, respectively. These results suggest that WEPO can inhibit cell pyroptosis caused by PEDV and that the Caspase-1 and GSDMD pathways play an important role in this process. Full article

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18 pages, 7733 KiB

Open AccessArticle

Ginkgo biloba: Antioxidant Activity and In Silico Central Nervous System Potential

by Eduardo Suárez-González, Jesús Sandoval-Ramírez, Jorge Flores-Hernández and Alan Carrasco-Carballo

Curr. Issues Mol. Biol. 2023, 45(12), 9674-9691; https://doi.org/10.3390/cimb45120604 - 1 Dec 2023

Cited by 3 | Viewed by 2207

Abstract

Ginkgo biloba (GB) extracts have been used in clinical studies as an alternative therapy for Alzheimer’s disease (AD), but the exact bioaction mechanism has not yet been elucidated. In this work, an in silico study on GB metabolites was carried out using SwissTargetPrediction [...] Read more.

Ginkgo biloba (GB) extracts have been used in clinical studies as an alternative therapy for Alzheimer’s disease (AD), but the exact bioaction mechanism has not yet been elucidated. In this work, an in silico study on GB metabolites was carried out using SwissTargetPrediction to determine the proteins associated with AD. The resulting proteins, AChE, MAO-A, MAO-B, β-secretase and γ-secretase, were studied by molecular docking, resulting in the finding that kaempferol, quercetin, and luteolin have multitarget potential against AD. These compounds also exhibit antioxidant activity towards reactive oxygen species (ROS), so antioxidant tests were performed on the extracts using the DPPH and ABTS techniques. The ethanol and ethyl acetate GB extracts showed an important inhibition percentage, higher than 80%, at a dose of 0.01 mg/mL. The effect of GB extracts on AD resulted in multitarget action through two pathways: firstly, inhibiting enzymes responsible for degrading neurotransmitters and forming amyloid plaques; secondly, decreasing ROS in the central nervous system (CNS), reducing its deterioration, and promoting the formation of amyloid plaques. The results of this work demonstrate the great potential of GB as a medicinal plant. Full article

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19 pages, 4555 KiB

Open AccessArticle

Ouabain Induces Transcript Changes and Activation of RhoA/ROCK Signaling in Cultured Epithelial Cells (MDCK)

by Jacqueline Martínez-Rendón, Lorena Hinojosa, Beatriz Xoconostle-Cázares, José Abrahán Ramírez-Pool, Aída Castillo, Marcelino Cereijido and Arturo Ponce

Curr. Issues Mol. Biol. 2023, 45(9), 7538-7556; https://doi.org/10.3390/cimb45090475 - 14 Sep 2023

Cited by 2 | Viewed by 1988

Abstract

Ouabain, an organic compound with the ability to strengthen the contraction of the heart muscle, was originally derived from plants. It has been observed that certain mammalian species, including humans, naturally produce ouabain, leading to its classification as a new type of hormone. [...] Read more.

Ouabain, an organic compound with the ability to strengthen the contraction of the heart muscle, was originally derived from plants. It has been observed that certain mammalian species, including humans, naturally produce ouabain, leading to its classification as a new type of hormone. When ouabain binds to Na⁺/K⁺-ATPase, it elicits various physiological effects, although these effects are not well characterized. Previous studies have demonstrated that ouabain, within the concentration range found naturally in the body (10 nmol/L), affects the polarity of epithelial cells and their intercellular contacts, such as tight junctions, adherens junctions, and gap junctional communication. This is achieved by activating signaling pathways involving cSrc and Erk1/2. To further investigate the effects of ouabain within the hormonally relevant concentration range (10 nmol/L), mRNA-seq, a high-throughput sequencing technique, was employed to identify differentially expressed transcripts. The discovery that the transcript encoding MYO9A was among the genes affected prompted an exploration of whether RhoA and its downstream effector ROCK were involved in the signaling pathways through which ouabain influences cell-to-cell contacts in epithelial cells. Supporting this hypothesis, this study reveals the following: (1) Ouabain increases the activation of RhoA. (2) Treatment with inhibitors of RhoA activation (Y27) and ROCK (C3) eliminates the enhancing effect of ouabain on the tight junction seal and intercellular communication via gap junctions. These findings further support the notion that ouabain acts as a hormone to emphasize the epithelial phenotype. Full article

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19 pages, 6264 KiB

Open AccessArticle

Mechanism of Taxanes in the Treatment of Lung Cancer Based on Network Pharmacology and Molecular Docking

by Yajing Zhang, Zirui Zhao, Wenlong Li, Yuanhu Tang and Shujie Wang

Curr. Issues Mol. Biol. 2023, 45(8), 6564-6582; https://doi.org/10.3390/cimb45080414 - 7 Aug 2023

Cited by 1 | Viewed by 2378

Abstract

Taxanes are natural compounds for the treatment of lung cancer, but the molecular mechanism behind the effects is unclear. In the present study, through network pharmacology and molecular docking, the mechanism of the target and pathway of taxanes in the treatment of lung [...] Read more.

Taxanes are natural compounds for the treatment of lung cancer, but the molecular mechanism behind the effects is unclear. In the present study, through network pharmacology and molecular docking, the mechanism of the target and pathway of taxanes in the treatment of lung cancer was studied. The taxanes targets were determined by PubChem database, and an effective compounds-targets network was constructed. The GeneCards database was used to determine the disease targets of lung cancer, and the intersection of compound targets and disease targets was obtained. The Protein–Protein Interaction (PPI) network of the intersection targets was analyzed, and the PPI network was constructed by Cytoscape 3.6.0 software. The hub targets were screened according to the degree value, and the binding activity between taxanes and hub targets was verified by molecular docking. The results showed that eight taxane-active compounds and 444 corresponding targets were screened out, and 131 intersection targets were obtained after mapping with lung cancer disease targets. The hub targets obtained by PPI analysis were TP53, EGFR, and AKT1. Gene Ontology (GO) biological function enrichment analysis obtained 1795 biological process (BP) terms, 101 cellular component (CC) terms, and 164 molecular function (MF) terms. There were 179 signaling pathways obtained by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Twenty signaling pathways were screened out, mainly pathways in cancer, proteoglycans in cancer pathway, microRNAs in cancer pathway, and so on. Molecular docking shows that the binding energies of eight taxanes with TP53, EGFR, and AKT1 targets were less than −8.8 kcal/mol, taxanes acts on TP53, EGFR, and AKT1 targets through pathways in cancer, proteoglycans in cancer pathway and microRNAs in cancer pathway, and plays a role in treating lung cancer in biological functions such as protein binding, enzyme binding, and identical protein binding. Full article

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17 pages, 7823 KiB

Open AccessArticle

Antidiabetic Effect of Fermented Mesembryanthemum crystallinum L. in db/db Mice Involves Regulation of PI3K-Akt Pathway

by Hye-Lin Kim, Yunu Jung, Hyo In Kim, Nak-Yun Sung, Min-Jee Kim, In-Jun Han, Geon Kim, Eun Yeong Nho, Sang-Yun Park, Yohan Han, Ji Hoon Jung, Dong-Sub Kim and Jinbong Park

Curr. Issues Mol. Biol. 2023, 45(8), 6415-6431; https://doi.org/10.3390/cimb45080405 - 3 Aug 2023

Cited by 3 | Viewed by 2053

Abstract

Type 2 diabetes (T2D) is a serious health issue with increasing incidences worldwide. However, current medications have limitations due to side effects such as decreased appetite, stomach pain, diarrhea, and extreme tiredness. Here, we report the effect of fermented ice plant (FMC) in [...] Read more.

Type 2 diabetes (T2D) is a serious health issue with increasing incidences worldwide. However, current medications have limitations due to side effects such as decreased appetite, stomach pain, diarrhea, and extreme tiredness. Here, we report the effect of fermented ice plant (FMC) in the T2M mouse model of db/db mice. FMC showed a greater inhibition of lipid accumulation compared to unfermented ice plant extract. Two-week oral administration with FMC inhibited body weight gain, lowered fasting blood glucose, and improved glucose tolerance. Serum parameters related to T2D including insulin, glycosylated hemoglobin, adiponectin, and cholesterols were improved as well. Histological analysis confirmed the protective effect of FMC on pancreas and liver destruction. FMC treatment significantly increased the expression and phosphorylation of IRS-1, PI3K, and AKT. Additionally, AMP-activated protein kinase phosphorylation and nuclear factor erythroid 2–related factor 2 were also increased in the liver tissues of db/db mice treated with FMC. Overall, our results indicate the anti-diabetic effect of FMC; therefore, we suggest that FMC may be useful as a therapeutic agent for T2D. Full article

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16 pages, 3360 KiB

Open AccessArticle

Cymbopogon citratus Essential Oil: Extraction, GC–MS, Phytochemical Analysis, Antioxidant Activity, and In Silico Molecular Docking for Protein Targets Related to CNS

by Ana G. Cortes-Torres, Guiee N. López-Castillo, Josefina L. Marín-Torres, Roberto Portillo-Reyes, Felix Luna, Beatriz E. Baca, Jesús Sandoval-Ramírez and Alan Carrasco-Carballo

Curr. Issues Mol. Biol. 2023, 45(6), 5164-5179; https://doi.org/10.3390/cimb45060328 - 16 Jun 2023

Cited by 6 | Viewed by 4097

Abstract

This study analyzed the chemical composition of Cymbopogon citratus essential oil from Puebla, México, assessed its antioxidant activity, and evaluated in silico protein–compound interactions related to central nervous system (CNS) physiology. GC–MS analysis identified myrcene (8.76%), Z-geranial (27.58%), and E-geranial (38.62%) as the [...] Read more.

This study analyzed the chemical composition of Cymbopogon citratus essential oil from Puebla, México, assessed its antioxidant activity, and evaluated in silico protein–compound interactions related to central nervous system (CNS) physiology. GC–MS analysis identified myrcene (8.76%), Z-geranial (27.58%), and E-geranial (38.62%) as the main components, with 45 other compounds present, which depends on the region and growing conditions. DPPH and Folin–Ciocalteu assays using the leaves extract show a promising antioxidant effect (EC₅₀ = 48.5 µL EO/mL), reducing reactive oxygen species. The bioinformatic tool SwissTargetPrediction (STP) shows 10 proteins as potential targets associated with CNS physiology. Moreover, protein–protein interaction diagrams suggest that muscarinic and dopamine receptors are related to each other through a third party. Molecular docking reveals that Z-geranial has higher binding energy than M1 commercial blocker and blocks M2, but not M4 muscarinic acetylcholine receptors, whereas β-pinene and myrcene block M1, M2, and M4 receptors. These actions may positively affect cardiovascular activity, memory, Alzheimer’s disease, and schizophrenia. This study highlights the significance of understanding natural product interactions with physiological systems to uncover potential therapeutic agents and advanced knowledge on their benefits for human health. Full article

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13 pages, 2969 KiB

Open AccessArticle

Hair Growth Effect of DN106212 in C57BL/6 Mouse and Its Network Pharmacological Mechanism of Action

by Ji Yun Baek, Byoung Ha Kim, Dong-Wook Kim, Won-Yung Lee, Chang Eop Kim, Hyun-Young Kim, Jaesung Pyo, Eun-Seok Park and Ki Sung Kang

Curr. Issues Mol. Biol. 2023, 45(6), 5071-5083; https://doi.org/10.3390/cimb45060322 - 9 Jun 2023

Cited by 3 | Viewed by 4579

Abstract

Centipeda minima (CMX) has been widely investigated using network pharmacology and clinical studies for its effects on hair growth via the JAK/STAT signaling pathway. Human hair follicle papilla cells exhibit hair regrowth through the expression of Wnt signaling-related proteins. However, the mechanism of [...] Read more.

Centipeda minima (CMX) has been widely investigated using network pharmacology and clinical studies for its effects on hair growth via the JAK/STAT signaling pathway. Human hair follicle papilla cells exhibit hair regrowth through the expression of Wnt signaling-related proteins. However, the mechanism of action of CMX in animals has not been elucidated fully. This study examined the effect of induced hair loss and its side-effects on the skin, and observed the mechanism of action of an alcoholic extract of CMX (DN106212) on C57BL/6 mice. Our results showed that DN106212 was more effective in promoting hair growth than dimethyl sulfoxide in the negative control and tofacitinib (TF) in the positive control when mice were treated with DN106212 for 16 days. We confirmed that DN106212 promotes the formation of mature hair follicles through hematoxylin and eosin staining. We also found that the expression of vascular endothelial growth factor (Vegfa), insulin-like growth factor 1 (Igf1), and transforming growth factor beta 1 (Tgfb1) is related to hair growth using PCR. DN106212-treated mice had significantly higher expression of Vegfa and Igf1 than TF-treated ones, and inhibiting the expression of Tgfb1 had similar effects as TF treatment. In conclusion, we propose that DN106212 increases the expression of hair growth factors, promotes the development of hair follicles, and promotes hair growth. Although additional experiments are needed, DN106212 may serve as an experimental basis for research on natural hair growth-promoting agents. Full article

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15 pages, 7123 KiB

Open AccessArticle

Biochemical and Antioxidant Properties as well as Antimicrobial and Antibiofilm Activities of Allium scorodoprasum subsp. jajlae (Vved.) Stearn

by Kerem Canli, Dilay Turu, Atakan Benek, Mustafa Eray Bozyel, Özcan Simsek and Ergin Murat Altuner

Curr. Issues Mol. Biol. 2023, 45(6), 4970-4984; https://doi.org/10.3390/cimb45060316 - 7 Jun 2023

Cited by 1 | Viewed by 1595

Abstract

In this study, the chemical composition and biological activity of Allium scorodoprasum subsp. jajlae (Vved.) Stearn were investigated for the first time, focusing on its antimicrobial, antioxidant, and antibiofilm properties. A GC-MS analysis was employed to evaluate the composition of its secondary metabolites, [...] Read more.

In this study, the chemical composition and biological activity of Allium scorodoprasum subsp. jajlae (Vved.) Stearn were investigated for the first time, focusing on its antimicrobial, antioxidant, and antibiofilm properties. A GC-MS analysis was employed to evaluate the composition of its secondary metabolites, identifying linoleic acid, palmitic acid, and octadecanoic acid 2,3-dihydroxypropyl ester as the major compounds in ethanol extract. The antimicrobial activity of A. scorodoprasum subsp. jajlae was assessed against 26 strains, including standard, food isolate, clinical isolate, and multidrug-resistant ones, as well as three Candida species using the disc diffusion method and the determination of the minimum inhibitory concentration (MIC). The extract showed strong antimicrobial activity against Staphylococcus aureus strains, including methicillin-resistant and multidrug-resistant strains, as well as Candida tropicalis and Candida glabrata. Its antioxidant capacity was evaluated using the DPPH method, revealing a high level of antioxidant activity in the plant. Additionally, the antibiofilm activity of A. scorodoprasum subsp. jajlae was determined, demonstrating a reduction in biofilm formation for the Escherichia coli ATCC 25922 strain and an increase in biofilm formation for the other tested strains. The findings suggest potential applications of A. scorodoprasum subsp. jajlae in the development of novel antimicrobial, antioxidant, and antibiofilm agents. Full article

15 pages, 50142 KiB

Open AccessCommunication

Quercetin Alleviates Pulmonary Fibrosis in Silicotic Mice by Inhibiting Macrophage Transition and TGF-β-Smad2/3 Pathway

by Fei Geng, Lan Zhao, Yuhao Cai, Ying Zhao, Fuyu Jin, Yaqian Li, Tian Li, Xinyu Yang, Shifeng Li, Xuemin Gao, Wenchen Cai, Na Mao, Ying Sun, Hong Xu, Zhongqiu Wei and Fang Yang

Curr. Issues Mol. Biol. 2023, 45(4), 3087-3101; https://doi.org/10.3390/cimb45040202 - 5 Apr 2023

Cited by 10 | Viewed by 2903

Abstract

Silicosis is a pulmonary disease caused by the inhalation of silica. There is a lack of early and effective prevention, diagnosis, and treatment methods, and addressing silicotic fibrosis is crucial. Quercetin, a flavonoid with anti-carcinogenic, anti-inflammatory, and antiviral properties, is known to have [...] Read more.

Silicosis is a pulmonary disease caused by the inhalation of silica. There is a lack of early and effective prevention, diagnosis, and treatment methods, and addressing silicotic fibrosis is crucial. Quercetin, a flavonoid with anti-carcinogenic, anti-inflammatory, and antiviral properties, is known to have a suppressive effect on fibrosis. The present study aimed to determine the therapeutic effect of quercetin on silicotic mice and macrophage polarity. We found that quercetin suppressed silicosis in mice. It was observed that SiO₂ activated macrophage polarity and the macrophage-to-myofibroblast transition (MMT) by transforming the growth factor-β (TGF-β)-Smad2/3 signaling pathway in silicotic mice and MH-S cells. Quercetin also attenuated the MMT and the TGF-β-Smad2/3 signaling pathway in vivo and in vitro. The present study demonstrated that quercetin is a potential therapeutic agent for silicosis, which acts by regulating macrophage polarity and the MMT through the TGF-β-Smad2/3 signaling pathway. Full article

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19 pages, 1918 KiB

Open AccessArticle

Changes in the Expression Profile of Pyroptosis-Related Genes in Senescent Retinal Pigment Epithelial Cells after Lutein Treatment

by Barbara Strzalka-Mrozik, Marcel Madej, Natalia Kurowska, Celina Kruszniewska-Rajs, Magdalena Kimsa-Dudek, Jolanta Adamska and Joanna Magdalena Gola

Curr. Issues Mol. Biol. 2023, 45(2), 1500-1518; https://doi.org/10.3390/cimb45020097 - 9 Feb 2023

Cited by 6 | Viewed by 2476

Abstract

Retinal pigment epithelium (RPE) is a specialized structure essential for proper vision, which is constantly exposed to oxidative damage. With aging, this damage accumulates within the RPE cells, causing various diseases, including age-related macular degeneration (AMD). Numerous antioxidant substances are used to prevent [...] Read more.

Retinal pigment epithelium (RPE) is a specialized structure essential for proper vision, which is constantly exposed to oxidative damage. With aging, this damage accumulates within the RPE cells, causing various diseases, including age-related macular degeneration (AMD). Numerous antioxidant substances are used to prevent this process in humans, including lutein. This study aims to determine the differences in the expression patterns of pyroptosis genes in senescent human retinal pigment epithelial cell line ARPE-19 exposed to lutein. Changes in the expression of pyroptosis-related genes were assessed by oligonucleotide microarrays, and the results were validated by real-time RT-qPCR. The microarray analysis showed seven transcripts were differentially expressed both in the H₂O₂-treated cells versus the controls and in the lutein/H₂O₂-treated cells compared to the H₂O₂-treated cells (FC > 2.0). Depending on the used lutein, H₂O₂, or co-treatment of ARPE-19 cells, statistically significant differences in the expression of TXNIP, CXCL8, BAX, and CASP1 genes were confirmed by the RT-qPCR (p < 0.05). A STRING database analysis showed that the proteins encoded by the analyzed genes form a strong interaction network (p < 0.001). These data indicate that lutein modulates the expression level of pyroptosis-related genes, which may be useful for the development of new methods preventing pyroptosis pathway activation in the future. Full article

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8 pages, 364 KiB

Open AccessArticle

In Vitro Antiviral Evaluations of Coldmix^®: An Essential Oil Blend against SARS-CoV-2

by Kemal Hüsnü Can Başer, Ayşe Esra Karadağ, Sevde Nur Biltekin, Murat Ertürk and Fatih Demirci

Curr. Issues Mol. Biol. 2023, 45(1), 677-684; https://doi.org/10.3390/cimb45010045 - 11 Jan 2023

Viewed by 2538

Abstract

Coldmix^® is a commercially available Eucalyptus aetheroleum and, Abies aetheroleum blend for medicinal applications. In this present study, the in vitro antiviral potential of Coldmix^®, and its major constituents 1,8-cineole and α-pinene were evaluated by using the in vitro ACE2 [...] Read more.

Coldmix^® is a commercially available Eucalyptus aetheroleum and, Abies aetheroleum blend for medicinal applications. In this present study, the in vitro antiviral potential of Coldmix^®, and its major constituents 1,8-cineole and α-pinene were evaluated by using the in vitro ACE2 enzyme inhibition assay as well as the direct contact test against SARS-CoV-2. The observed ACE2 enzyme inhibitory activity of Coldmix^®, 1,8-cineole, and α-pinene were 72%, 88%, and 80%, respectively; whereas in the direct contact test in the vapor phase, the destruction of the virus was 79.9% within 5 min and 93.2% in the 30th min, respectively. In a similar Coldmix^® vapor phase setup using the in vitro cytotoxicity cell assay, E6 VERO healthy cells were experimentally not affected by toxicity. According to the promising initial antiviral results of Coldmix^® and the individually tested constituents, detailed further in vivo evaluation using different virus classes is suggested. Full article

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16 pages, 10172 KiB

Open AccessArticle

Deciphering the Mechanism of Wogonin, a Natural Flavonoid, on the Proliferation of Pulmonary Arterial Smooth Muscle Cells by Integrating Network Pharmacology and In Vitro Validation

by Lidan Cui, Zuomei Zeng, Xinyue Wang, Tianyi Yuan, Can Wang, Dianlong Liu, Jian Guo and Yucai Chen

Curr. Issues Mol. Biol. 2023, 45(1), 555-570; https://doi.org/10.3390/cimb45010037 - 8 Jan 2023

Cited by 4 | Viewed by 2957

Abstract

Wogonin is one of the main active components of Scutellaria baicalensis, which has anti-inflammatory, anti-angiogenesis, and anti-fibrosis effects. Nevertheless, the effect of wogonin on pulmonary hypertension (PH) still lacks systematic research. This study aims to elucidate the potential mechanism of wogonin against [...] Read more.

Wogonin is one of the main active components of Scutellaria baicalensis, which has anti-inflammatory, anti-angiogenesis, and anti-fibrosis effects. Nevertheless, the effect of wogonin on pulmonary hypertension (PH) still lacks systematic research. This study aims to elucidate the potential mechanism of wogonin against PH through network pharmacology and further verify it through biological experiments in pulmonary arterial smooth muscle cells (PASMCs). The potential targets and pathways of wogonin against PH were predicted and analyzed by network pharmacology methods and molecular docking technology. Subsequently, the proliferation of PASMCs was induced by platelet-derived growth factor-BB (PDGF-BB). Cell viability and migration ability were examined. The method of Western blot was adopted to analyze the changes in related signaling pathways. Forty potential targets related to the effect of wogonin against PH were obtained. Based on the protein–protein interaction (PPI) network, gene-ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment, and molecular docking, it was shown that the effect of wogonin against PH is closely related to the proliferation of PASMCs and the hypoxia-inducible factor-1α (HIF-1α) pathway. A variety of results from biological experiments verified that wogonin can effectively inhibit the proliferation, migration, and phenotypic transformation of PDGF-BB-mediated PASMCs. In addition, the anti-proliferation effect of wogonin may be achieved by regulating HIF-1/ NADPH oxidase 4 (NOX4) pathway. Full article

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15 pages, 3458 KiB

Open AccessArticle

Lavender Essential Oil Modulates Hepatic Cholesterol Metabolism in HepG2 Cells

by Noemi Martella, Mayra Colardo, William Sergio, Michele Petraroia, Michela Varone, Daniele Pensabene, Miriam Russo, Sabrina Di Bartolomeo, Giancarlo Ranalli, Gabriella Saviano and Marco Segatto

Curr. Issues Mol. Biol. 2023, 45(1), 364-378; https://doi.org/10.3390/cimb45010026 - 3 Jan 2023

Cited by 2 | Viewed by 4015

Abstract

Cholesterol is an essential lipid that guarantees several biological processes in eukaryotic cells. Its metabolism is regulated by a complex protein network that could be significantly influenced by numerous exogenous sources, such as essential oils (EOs). For instance, it has been speculated that [...] Read more.

Cholesterol is an essential lipid that guarantees several biological processes in eukaryotic cells. Its metabolism is regulated by a complex protein network that could be significantly influenced by numerous exogenous sources, such as essential oils (EOs). For instance, it has been speculated that monoterpenoid and sesquiterpenoid compounds contained in lavender essential oil (LEO) may exert important hypocholesterolemic activities. However, the molecular mechanisms by which LEO influences cholesterol homeostasis are not characterized. In this work, we evaluated the ability of LEO to regulate the protein network that controls cholesterol metabolism in the HepG2 cell line. The main findings indicate that LEO administration increases intracellular cholesterol content. Concurrently, LEO affects the expression of proteins involved in cholesterol uptake, biosynthesis, and trafficking. These effects are partially mediated by terpinene-4-ol, one of the most abundant compounds in LEO. These results demonstrate that LEO modulates cholesterol metabolism in hepatic cells. Full article

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2022

Jump to: 2024, 2023, 2021

18 pages, 3977 KiB

Open AccessArticle

Design, Synthesis, Characterization, and Analysis of Antimicrobial Property of Novel Benzophenone Fused Azetidinone Derivatives through In Vitro and In Silico Approach

by Lakshmi Ranganatha Venkataravanappa, Mahima Jyothi, Hussien Ahmed Khamees, Ekaterina Silina, Victor Stupin, Raghu Ram Achar, Mohammed Al-Ghorbani and Shaukath Ara Khanum

Curr. Issues Mol. Biol. 2023, 45(1), 92-109; https://doi.org/10.3390/cimb45010007 - 23 Dec 2022

Cited by 4 | Viewed by 3057

Abstract

A sequence of novel 2-(4-benzoyl-2-methyl-phenoxy)-N-(3-chloro-2-oxo-4-phenyl-azetidin-1-yl)-acetamide analogues 9(a–n) were synthesized by multistep synthesis. The newly synthesized compounds were well characterized, and their antimicrobial activities were carried out by disc diffusion and broth dilution methods. Further, all the novel series of compounds (9a– [...] Read more.

A sequence of novel 2-(4-benzoyl-2-methyl-phenoxy)-N-(3-chloro-2-oxo-4-phenyl-azetidin-1-yl)-acetamide analogues 9(a–n) were synthesized by multistep synthesis. The newly synthesized compounds were well characterized, and their antimicrobial activities were carried out by disc diffusion and broth dilution methods. Further, all the novel series of compounds (9a–n), were tested against a variety of bacterial and fungal strains in comparison to Ketoconazole, Chloramphenicol, and Amoxicillin as standard drugs, respectively. Compounds 9a, 9e, and 9g as a lead molecule demonstrated a good inhibition against tested strains. Further, molecular docking studies have been performed for the potent compounds to check the three-dimensional geometrical view of the ligand binding to the targeted proteins. Full article

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17 pages, 3250 KiB

Open AccessArticle

Design, Synthesis, and Bioactivity of Novel Quinazolinone Scaffolds Containing Pyrazole Carbamide Derivatives as Antifungal Agents

by Zhiwei Lei, Jianmei Yao, Huifang Liu, Xianjin Bai, Xingsi Gao, Qiuyuan Pan and Wen Yang

Curr. Issues Mol. Biol. 2022, 44(11), 5605-5621; https://doi.org/10.3390/cimb44110380 - 12 Nov 2022

Cited by 4 | Viewed by 2282

Abstract

In this study, 32 novel quinazolinone-scaffold-containing pyrazole carbamide derivatives were designed and synthesized in a search for a novel fungicide against Rhizoctonia solani. Single-crystal X-ray diffraction of 3-(difluoromethyl)-N-(2-((6,7-difluoro-4-oxoquinazolin-3(4H)-yl)methyl)phenyl)-1-methyl-1H-pyrazole-4-carboxamide (6a₁₁) confirmed the structure of the target compounds. The [...] Read more.

In this study, 32 novel quinazolinone-scaffold-containing pyrazole carbamide derivatives were designed and synthesized in a search for a novel fungicide against Rhizoctonia solani. Single-crystal X-ray diffraction of 3-(difluoromethyl)-N-(2-((6,7-difluoro-4-oxoquinazolin-3(4H)-yl)methyl)phenyl)-1-methyl-1H-pyrazole-4-carboxamide (6a₁₁) confirmed the structure of the target compounds. The in vitro antifungal activity of the target compounds against R. solani was evaluated at 100 µg/mL. The structure–activity relationship analysis results revealed that antifungal activity was highest when the substitution activity was at position 6. Moreover, the position and number of chlorine atoms directly affected the antifungal activity. Further in vitro bioassays revealed that 6a₁₆ (EC₅₀ = 9.06 mg/L) had excellent antifungal activity against R. solani that was higher than that of the commercial fungicide fluconazole (EC₅₀ = 12.29 mg/L) but lower than that of bixafen (EC₅₀ = 0.34 mg/L). Scanning electron microscopy), 7.33 (SEM) revealed that N-(2-((6,8-dichloro-4-oxoquinazolin-3(4H)-yl)methyl)phenyl)-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide (6a₁₆) also affected the mycelial morphology. The findings revealed that molecular hybridization was an effective tool for designing antifungal candidates. Meanwhile, pyrazolecarbamide derivatives bearing a quinazolinone fragment exhibited potential antifungal activity against R. solani. Full article

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19 pages, 81249 KiB

Open AccessArticle

Cytotoxic Potential of Alternaria tenuissima AUMC14342 Mycoendophyte Extract: A Study Combined with LC-MS/MS Metabolic Profiling and Molecular Docking Simulation

by Amal A. Al Mousa, Mohamed E. Abouelela, Abdallah M. A. Hassane, Fatimah S. Al-Khattaf, Ashraf A. Hatamleh, Hadeel S. Alabdulhadi, Noura D. Dahmash and Nageh F. Abo-Dahab

Curr. Issues Mol. Biol. 2022, 44(10), 5067-5085; https://doi.org/10.3390/cimb44100344 - 20 Oct 2022

Cited by 6 | Viewed by 2404

Abstract

Breast, cervical, and ovarian cancers are among the most serious cancers and the main causes of mortality in females worldwide, necessitating urgent efforts to find newer sources of safe anticancer drugs. The present study aimed to evaluate the anticancer potency of mycoendophytic Alternaria [...] Read more.

Breast, cervical, and ovarian cancers are among the most serious cancers and the main causes of mortality in females worldwide, necessitating urgent efforts to find newer sources of safe anticancer drugs. The present study aimed to evaluate the anticancer potency of mycoendophytic Alternaria tenuissima AUMC14342 ethyl acetate extract on HeLa (cervical cancer), SKOV-3 (ovarian cancer), and MCF-7 (breast adenocarcinoma) cell lines. The extract showed potent effect on MCF-7 cells with an IC50 value of 55.53 μg/mL. Cell cycle distribution analysis of treated MCF-7 cells revealed a cell cycle arrest at the S phase with a significant increase in the cell population (25.53%). When compared to control cells, no significant signs of necrotic or apoptotic cell death were observed. LC-MS/MS analysis of Alternaria tenuissima extract afforded the identification of 20 secondary metabolites, including 7-dehydrobrefeldin A, which exhibited the highest interaction score (−8.0156 kcal/mol) in molecular docking analysis against human aromatase. Regarding ADME pharmacokinetics and drug-likeness properties, 7-dehydrobrefeldin A, 4’-epialtenuene, and atransfusarin had good GIT absorption and water solubility without any violation of drug-likeness rules. These findings support the anticancer activity of bioactive metabolites derived from endophytic fungi and provide drug scaffolds and substitute sources for the future development of safe chemotherapy. Full article

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19 pages, 4537 KiB

Open AccessArticle

Protective Effects of One 2,4-Dihydro-3H-Pyrazol-3-one Derivative against Posterior Capsular Opacification by Regulation of TGF-β2/SMADs and Non-SMAD Signaling, Collagen I, and Fibronectin Proteins

by Chun-Ching Shih, Chia-Yi Lee, Fung-Fuh Wong and Cheng-Hsiu Lin

Curr. Issues Mol. Biol. 2022, 44(10), 5048-5066; https://doi.org/10.3390/cimb44100343 - 19 Oct 2022

Cited by 3 | Viewed by 2230

Abstract

Many elderly individuals frequently experience cataracts that interfere with vision. After cataract surgery, the left lens epithelial cell (LEC) exhibited fibrosis and posterior capsule opacification (PCO). Sometimes, there is a need for a second surgery; nevertheless, people try other methods, such as a [...] Read more.

Many elderly individuals frequently experience cataracts that interfere with vision. After cataract surgery, the left lens epithelial cell (LEC) exhibited fibrosis and posterior capsule opacification (PCO). Sometimes, there is a need for a second surgery; nevertheless, people try other methods, such as a good pharmacological agent, to treat PCO to reduce transforming growth factor-β2 (TGF-β2) amounts to avoid secondary surgery. The aim of the present study was to explore the potential anti-PCO activity of five 2,4-dihydro-3H-pyrazol-3-one (DHPO) derivatives in a TGF-β2-induced fibrogenesis SRA01/04 cell model. The 2-phenyl-5-propyl-DHPO (TSE; no. 2: TSE-2) compound showed the best activity of reduced expression levels of TGF-β2 among five derivatives and therefore was chosen to evaluate the anti-PCO activity and molecular mechanisms on the Sma and mad protein (SMAD) signaling pathway (including TGF-β2, SMADs, and the inhibition of nuclear translocation of SMADs), non-SMAD pathway proteins, including p-extracellular, regulated protein kinases (ERK) 1/2, or p-c-Jun N-terminal kinase (JUN) by Western blotting, PCR, or confocal immunofluorescence analyses. Following treatment with 10 μg/mL of the five compounds, the cells displayed great viability by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTT) assay. In this study, the result of lactate dehydrogenase (LDH) activity measurement did not affect the cytotoxicity of the five compounds. In TGF-β2-induced fibrogenesis in SRA01/04 cells, treatment with the TSE compound decreased the TGF-β2/SMAD signaling genes, including reduced mRNA or expression levels of TGF-β2, SMAD3, and SMAD4, leading to inhibition of TGF-β2-induced fibrogenesis. Our confocal immunofluorescence analyses demonstrated that TSE treatment displays a suppressive effect on SMAD2/3 or SMAD4 translocation to the nucleus. Furthermore, TSE treatment exhibits a reduction in the non-SMAD target gene expression levels of p- c-Jun N-terminal kinase (JUN), p- extracellular, regulated protein kinases (ERK)1/2, p- p38 mitogen-activated protein kinase (p38), p-phosphatidylinositol 3-kinase (PI3K), p-mammalian target of rapamycin complex (mTORC), p-Akt (Ser⁴⁷³), and p-Akt (Thr³⁰⁸). The overall effect of TSE is to reduce the expression levels of collagen I and fibrinogen (FN), thus contributing to antifibrotic effects in cell models mimicking PCO. Our findings reveal the benefits of TSE by regulating TGF-β/SMAD signaling and non-SMAD signaling-related gene proteins to display antifibrotic activity in cells for the possibility of preventing PCO after cataract surgery. Full article

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10 pages, 4131 KiB

Open AccessArticle

Proposed Mechanism for Emodin as Agent for Methicillin Resistant Staphylococcus Aureus: In Vitro Testing and In Silico Study

by Mohammed M. Ghoneim, Rasha Hamed Al-Serwi, Mohamed El-Sherbiny, El-sayed M. El-ghaly, Amal E. Hamad, Mohamed A. Abdelgawad, Ehab A. Ragab, Sarah I. Bukhari, Khulud Bukhari, Khaled Elokely and Manal A. Nael

Curr. Issues Mol. Biol. 2022, 44(10), 4490-4499; https://doi.org/10.3390/cimb44100307 - 27 Sep 2022

Cited by 3 | Viewed by 2241

Abstract

In the search for a new anti-MRSA lead compound, emodin was identified as a good lead against methicillin-resistant Staphylococcus aureus (MRSA). Emodin serves as a new scaffold to design novel and effective anti-MRSA agents. Because rational drug discovery is limited by the knowledge [...] Read more.

In the search for a new anti-MRSA lead compound, emodin was identified as a good lead against methicillin-resistant Staphylococcus aureus (MRSA). Emodin serves as a new scaffold to design novel and effective anti-MRSA agents. Because rational drug discovery is limited by the knowledge of the drug target, α-hemolysin of Staphylococcus aureus was used in this study because it has an essential role in Staphylococcus infections and because emodin shares structural features with compounds that target this enzyme. In order to explore emodin’s interactions with α-hemolysin, all possible ligand binding pockets were identified and investigated. Two ligand pockets were detected based on bound ligands and other reports. The third pocket was identified as a cryptic site after molecular dynamics (MD) simulations. MD simulations were conducted for emodin in each pocket to identify the most plausible ligand site and to aid in the design of potent anti-MRSA agents. Binding of emodin to site 1 was most stable (RMSD changes within 1 Å), while in site 2, the binding pose of emodin fluctuated, and it left after 20 ns. In site 3, it was stable during the first 50 ns, and then it started to move out of the binding site. Site 1 is a possible ligand binding pocket, and this study sheds more light on interaction types, binding mode, and key amino acids involved in ligand binding essential for better lead design. Emodin showed an IC₅₀ value of 6.3 μg/mL, while 1, 6, and 8 triacetyl emodin showed no activity against MRSA. A molecular modeling study was pursued to better understand effective binding requirements for a lead. Full article

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24 pages, 4896 KiB

Open AccessArticle

Evaluation of the Regenerative Potential of Platelet-Lysate and Platelet-Poor Plasma Derived from the Cord Blood Units in Corneal Wound Healing Applications: An In Vitro Comparative Study on Corneal Epithelial Cells

by Panagiotis Mallis, Efstathios Michalopoulos, Eirini Faidra Sarri, Elena Papadopoulou, Vasiliki Theodoropoulou, Michalis Katsimpoulas and Catherine Stavropoulos-Giokas

Curr. Issues Mol. Biol. 2022, 44(10), 4415-4438; https://doi.org/10.3390/cimb44100303 - 22 Sep 2022

Cited by 7 | Viewed by 2401

Abstract

Background: Cord blood platelet lysate (CB-PL) and cord blood platelet poor plasma (CB-PPP) have been applied with success in wound healing applications. Pathologies such as Sjogrens’s Syndrome (SS) and chronic graft versus host disease (cGVHD) can lead to severe ophthalmology issues. The application [...] Read more.

Background: Cord blood platelet lysate (CB-PL) and cord blood platelet poor plasma (CB-PPP) have been applied with success in wound healing applications. Pathologies such as Sjogrens’s Syndrome (SS) and chronic graft versus host disease (cGVHD) can lead to severe ophthalmology issues. The application of CB-PL and CB-PPP may be strongly considered for damaged cornea healing. This study aimed to the evaluation of the beneficial properties of CB-PL and CB-PPP in corneal wound healing applications. Methods: Initially, the CB-PL and CB-PPP were produced from donated cord blood units (CBUs), followed by biochemical analysis. Corneal epithelial cells (CECs) were isolated from wistar rats and then cultured with medium containing 20% v/v either of CB-PL or CB-PPP. To define the impact of CB-PL and CB-PPP, biochemical, morphological analysis, scratch-wound assays, and immunoassays in CECs were performed. Results: CB-PL and CB-PPP were characterized by good biochemical parameters, regarding their quality characteristics and biomolecule content. CECs’ morphological features did not change after their cultivation with CB-PL or CB-PPP. A scratch wound assay and molecular analysis of CECs expanded with CB-PL indicated higher migratory capacity compared to those cultured with CB-PPP. Conclusion: CB-PL and CB-PPP exhibited good properties with respect to cell migration and proliferation, and could be considered an alternative source for eye drop production, to possibly be used in cornea wound healing applications. Full article

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18 pages, 1088 KiB

Open AccessReview

A Concise Review of Extraction and Characterization of Chondroitin Sulphate from Fish and Fish Wastes for Pharmacological Application

by Zannat Urbi, Nina Suhaity Azmi, Long Chiau Ming and Md. Sanower Hossain

Curr. Issues Mol. Biol. 2022, 44(9), 3905-3922; https://doi.org/10.3390/cimb44090268 - 28 Aug 2022

Cited by 17 | Viewed by 4040

Abstract

Chondroitin sulphate (CS) is one of the most predominant glycosaminoglycans (GAGs) available in the extracellular matrix of tissues. It has many health benefits, including relief from osteoarthritis, antiviral properties, tissue engineering applications, and use in skin care, which have increased its commercial demand [...] Read more.

Chondroitin sulphate (CS) is one of the most predominant glycosaminoglycans (GAGs) available in the extracellular matrix of tissues. It has many health benefits, including relief from osteoarthritis, antiviral properties, tissue engineering applications, and use in skin care, which have increased its commercial demand in recent years. The quest for CS sources exponentially increased due to several shortcomings of porcine, bovine, and other animal sources. Fish and fish wastes (i.e., fins, scales, skeleton, bone, and cartilage) are suitable sources of CS as they are low cost, easy to handle, and readily available. However, the lack of a standard isolation and characterization technique makes CS production challenging, particularly concerning the yield of pure GAGs. Many studies imply that enzyme-based extraction is more effective than chemical extraction. Critical evaluation of the existing extraction, isolation, and characterization techniques is crucial for establishing an optimized protocol of CS production from fish sources. The current techniques depend on tissue hydrolysis, protein removal, and purification. Therefore, this study critically evaluated and discussed the extraction, isolation, and characterization methods of CS from fish or fish wastes. Biosynthesis and pharmacological applications of CS were also critically reviewed and discussed. Our assessment suggests that CS could be a potential drug candidate; however, clinical studies should be conducted to warrant its effectiveness. Full article

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11 pages, 3280 KiB

Open AccessArticle

Design, Synthesis, and Biological Evaluations of Novel Azothiazoles Based on Thioamide

by Abdelwahed R. Sayed, Hany Elsawy, Saad Shaaban, Sobhi M. Gomha and Yasair S. Al-Faiyz

Curr. Issues Mol. Biol. 2022, 44(7), 2956-2966; https://doi.org/10.3390/cimb44070204 - 1 Jul 2022

Cited by 9 | Viewed by 2193

Abstract

Herein we studied the preparation of different thiazoles via the reaction of 2-(3,4-dimethoxybenzylidene)hydrazine-1-carbothioamide (1) with hydrazonoyl halides under base-catalyzed conditions. The reactions proceed through nucleophilic substitution attack at the halogen atom of the hydrazonoyl halides by the thiol nucleophile to form [...] Read more.

Herein we studied the preparation of different thiazoles via the reaction of 2-(3,4-dimethoxybenzylidene)hydrazine-1-carbothioamide (1) with hydrazonoyl halides under base-catalyzed conditions. The reactions proceed through nucleophilic substitution attack at the halogen atom of the hydrazonoyl halides by the thiol nucleophile to form an S-alkylated intermediate. The latter intermediate undergoes cyclization by the loss of water to afford the final products. The structures of the azo compounds were confirmed by FTIR, MS, NMR, and elemental analyses. Indeed, the newly synthesized azo compounds were estimated for their potential anticancer activities by an MTT assay against different human cancer cells, such as lung adenocarcinoma (A549) and colorectal adenocarcinoma (DLD-1). The caspase-3 levels were also estimated using Western blotting and the dual staining technique to evaluate the potency of the titled compounds to promote apoptosis. Full article

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12 pages, 1184 KiB

Open AccessReview

The Protective Role of 4-Acetylarylquinolinol B in Different Pathological Processes

by Huijie Zhao, Huiyang Liu, Yihan Yang and Honggang Wang

Curr. Issues Mol. Biol. 2022, 44(5), 2362-2373; https://doi.org/10.3390/cimb44050161 - 23 May 2022

Viewed by 2249

Abstract

Antrodia cinnamomea is a traditional plant and a unique fungus native to Taiwan that has been reported to have many biological functions, including anti-inflammatory and anticancer activities. The compound 4-acetylarylquinolinol B (4-AAQB) is one of the main bioactive compounds in the stamens of [...] Read more.

Antrodia cinnamomea is a traditional plant and a unique fungus native to Taiwan that has been reported to have many biological functions, including anti-inflammatory and anticancer activities. The compound 4-acetylarylquinolinol B (4-AAQB) is one of the main bioactive compounds in the stamens of Antrodia cinnamomea, and has many biological functions, such as anti-inflammatory, antiproliferative, blood sugar reduction, antimetastasis, and vascular tone relaxation. In recent years, the increasing evidences have shown that 4-AAQB is involved in many diseases; however, the relevant mechanisms have not been fully clarified. This review aimed to clarify the improvement by 4-AAQB in different pathological processes, as well as the compound’s molecular mechanisms, in order to provide a theoretical reference for future related research Full article

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18 pages, 7066 KiB

Open AccessHypothesis

New Insight into Drugs to Alleviate Atopic March via Network Pharmacology-Based Analysis

by Ki-Kwang Oh, Md. Adnan and Dong-Ha Cho

Curr. Issues Mol. Biol. 2022, 44(5), 2257-2274; https://doi.org/10.3390/cimb44050153 - 18 May 2022

Cited by 1 | Viewed by 2716

Abstract

In the present study, a subject of atopic dermatitis (AD) is exposed progressively to allergic rhinitis (AR) and asthma (AS), which is defined as atopic march (AM). However, both the targets and compounds against AM are still largely unknown. Hence, we investigated the [...] Read more.

In the present study, a subject of atopic dermatitis (AD) is exposed progressively to allergic rhinitis (AR) and asthma (AS), which is defined as atopic march (AM). However, both the targets and compounds against AM are still largely unknown. Hence, we investigated the overlapping targets related directly to the occurrence and development of AD, AR, and AS through public databases (DisGeNET, and OMIM). The final overlapping targets were considered as key targets of AM, which were visualized by a Venn diagram. The protein–protein interaction (PPI) network was constructed using R package software. We retrieved the association between targets and ligands via scientific journals, and the ligands were filtered by physicochemical properties. Lastly, we performed a molecular docking test (MDT) to identify the significant ligand on each target. A total of 229 overlapping targets were considered as AM causal elements, and 210 out of them were interconnected with each other. We adopted 65 targets representing the top 30% highest in degree centrality among 210 targets. Then, we obtained 20 targets representing the top 30% greatest in betweenness centrality among 65 targets. The network analysis unveiled key targets against AM, and the MDT confirmed the affinity between significant compounds and targets. In this study, we described the significance of the eight uppermost targets (CCL2, CTLA4, CXCL8, ICAM1, IL10, IL17A, IL1B, and IL2) and eight ligands (Bindarit, CTLA-4 inhibitor, Danirixin, A-205804, AX-24 HCl, Y-320, T-5224, and Apilimod) against AM, providing a scientific basis for further experiments. Full article

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13 pages, 1327 KiB

Open AccessArticle

Antigenotoxic Effect of Ascorbic Acid and Resveratrol in Erythrocytes of Ambystoma mexicanum, Oreochromis niloticus and Human Lymphocytes Exposed to Glyphosate

by Carlos Alvarez-Moya, Alexis Gerardo Sámano-León, Mónica Reynoso-Silva, Rafael Ramírez-Velasco, Mario Alberto Ruiz-López and Alma Rosa Villalobos-Arámbula

Curr. Issues Mol. Biol. 2022, 44(5), 2230-2242; https://doi.org/10.3390/cimb44050151 - 17 May 2022

Cited by 5 | Viewed by 2574

Abstract

Glyphosate is a controversial herbicide. Its genotoxicity and presence in various ecosystems have been reported. The use of ascorbic acid and resveratrol could protect different organisms from glyphosate-induced genetic damage. In the present study, specific genetic damage induced by glyphosate was evaluated in [...] Read more.

Glyphosate is a controversial herbicide. Its genotoxicity and presence in various ecosystems have been reported. The use of ascorbic acid and resveratrol could protect different organisms from glyphosate-induced genetic damage. In the present study, specific genetic damage induced by glyphosate was evaluated in erythrocytes of Oreochromis niloticus, Ambystoma mexicanum and human lymphocytes. Simultaneously, the antigenotoxic capacity of various concentrations of ascorbic acid and resveratrol was evaluated by means of pretreatment and simultaneous treatment protocols. The 0.03, 0.05 and 0.07 mM concentrations of glyphosate induced significant genotoxic activity (p < 0.05) in human lymphocytes and in erythrocytes of the species studied, and could cause genomic instability in these populations. The reduction in genetic damage observed in human lymphocytes exposed to high concentrations of glyphosate is only apparent: excessive genetic damage was associated with undetectable excessive tail migration length. A significant (p < 0.05) antigenotoxic effect of ascorbic acid and resveratrol was observed in all concentrations, organisms and protocols used. Both ascorbic acid and resveratrol play an important role in maintaining the integrity of DNA. Ascorbic acid in Oreochromis niloticus, Ambystoma mexicanum reduced glyphosate-induced genetic damage to a basal level. Therefore, our data indicate that these antioxidants could help preserve the integrity of the DNA of organisms exposed to glyphosate. The consumption of antioxidants is a useful tool against the genotoxicity of glyphosate. Full article

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14 pages, 3601 KiB

Open AccessArticle

Punicalagin Targets Atherosclerosis: Gene Expression Profiling of THP-1 Macrophages Treated with Punicalagin and Molecular Docking

by Etimad Huwait, Sanaa Almowallad, Rehab Al-Massabi, Salma Saddeek, Kalamegam Gauthaman and Alexandre Prola

Curr. Issues Mol. Biol. 2022, 44(5), 2153-2166; https://doi.org/10.3390/cimb44050145 - 12 May 2022

Cited by 8 | Viewed by 2652

Abstract

Atherosclerosis is an important cause of cardiovascular disorders worldwide. Natural botanical drugs have attracted attention due to their antioxidant, anti-inflammatory, and antiatherogenic properties in the treatment of atherosclerosis. Punicalagin is the major bioactive component of pomegranate peel, and has been shown to have [...] Read more.

Atherosclerosis is an important cause of cardiovascular disorders worldwide. Natural botanical drugs have attracted attention due to their antioxidant, anti-inflammatory, and antiatherogenic properties in the treatment of atherosclerosis. Punicalagin is the major bioactive component of pomegranate peel, and has been shown to have antioxidant, anti-inflammatory, antiviral, anti proliferation, and anticancer properties. To explore its antiatherogenic properties at a molecular level, we investigated the genome-wide expression changes that occur in differentiated THP1 cells following treatment with a non-toxic dose of punicalagin. We also conducted a molecular docking simulation study to identify the molecular targets of punicalagin. Full article

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18 pages, 1991 KiB

Open AccessArticle

Subtilisin of Leishmania amazonensis as Potential Druggable Target: Subcellular Localization, In Vitro Leishmanicidal Activity and Molecular Docking of PF-429242, a Subtilisin Inhibitor

by Pollyanna Stephanie Gomes, Monique Pacheco Duarte Carneiro, Patrícia de Almeida Machado, Valter Viana de Andrade-Neto, Alessandra Marcia da Fonseca-Martins, Amy Goundry, João Vitor Marques Pereira da Silva, Daniel Claudio Oliveira Gomes, Ana Paula Cabral de Araujo Lima, Vítor Ennes-Vidal, Ana Carolina Rennó Sodero, Salvatore Giovanni De-Simone and Herbert L. de Matos Guedes

Curr. Issues Mol. Biol. 2022, 44(5), 2089-2106; https://doi.org/10.3390/cimb44050141 - 9 May 2022

Cited by 3 | Viewed by 3152

Abstract

Subtilisin proteases, found in all organisms, are enzymes important in the post-translational steps of protein processing. In Leishmania major and L. donovani, this enzyme has been described as essential to their survival; however, few compounds that target subtilisin have been investigated for [...] Read more.

Subtilisin proteases, found in all organisms, are enzymes important in the post-translational steps of protein processing. In Leishmania major and L. donovani, this enzyme has been described as essential to their survival; however, few compounds that target subtilisin have been investigated for their potential as an antileishmanial drug. In this study, we first show, by electron microscopy and flow cytometry, that subtilisin has broad localization throughout the cytoplasm and membrane of the parasite in the promastigote form with foci in the flagellar pocket. Through in silico analysis, the similarity between subtilisin of different Leishmania species and that of humans were determined, and based on molecular docking, we evaluated the interaction capacity of a serine protease inhibitor against both life cycle forms of Leishmania. The selected inhibitor, known as PF-429242, has already been used against the dengue virus, arenaviruses, and the hepatitis C virus. Moreover, it proved to have antilipogenic activity in a mouse model and caused hypolipidemia in human cells in vitro. Here, PF-429242 significantly inhibited the growth of L. amazonensis promastigotes of four different strains (IC₅₀ values = 3.07 ± 0.20; 0.83 ± 0.12; 2.02 ± 0.27 and 5.83 ± 1.2 µM against LTB0016, PH8, Josefa and LV78 strains) whilst having low toxicity in the host macrophages (CC₅₀ = 170.30 µM). We detected by flow cytometry that there is a greater expression of subtilisin in the amastigote form; however, PF-429242 had a low effect against this intracellular form with an IC50 of >100 µM for intracellular amastigotes, as well as against axenic amastigotes (94.12 ± 2.8 µM for the LV78 strain). In conclusion, even though PF-429242 does not affect the intracellular forms, this drug will serve as a tool to explore pharmacological and potentially leishmanicidal targets. Full article

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35 pages, 9443 KiB

Open AccessReview

Fruit Peels: Food Waste as a Valuable Source of Bioactive Natural Products for Drug Discovery

by Hidayat Hussain, Nilufar Z. Mamadalieva, Amjad Hussain, Uzma Hassan, Aisha Rabnawaz, Ishtiaq Ahmed and Ivan R. Green

Curr. Issues Mol. Biol. 2022, 44(5), 1960-1994; https://doi.org/10.3390/cimb44050134 - 30 Apr 2022

Cited by 26 | Viewed by 14492

Abstract

Fruits along with vegetables are crucial for a balanced diet. These not only have delicious flavors but are also reported to decrease the risk of contracting various chronic diseases. Fruit by-products are produced in huge quantity during industrial processing and constitute a serious [...] Read more.

Fruits along with vegetables are crucial for a balanced diet. These not only have delicious flavors but are also reported to decrease the risk of contracting various chronic diseases. Fruit by-products are produced in huge quantity during industrial processing and constitute a serious issue because they may pose a harmful risk to the environment. The proposal of employing fruit by-products, particularly fruit peels, has gradually attained popularity because scientists found that in many instances peels displayed better biological and pharmacological applications than other sections of the fruit. The aim of this review is to highlight the importance of fruit peel extracts and natural products obtained in food industries along with their other potential biological applications. Full article

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10 pages, 1630 KiB

Open AccessArticle

Palladium Phthalocyanines Varying in Substituents Position for Photodynamic Inactivation of Flavobacterium hydatis as Sensitive and Resistant Species

by Vanya Mantareva, Vesselin Kussovski, Petya Orozova, Ivan Angelov, Mahmut Durmuş and Hristo Najdenski

Curr. Issues Mol. Biol. 2022, 44(5), 1950-1959; https://doi.org/10.3390/cimb44050133 - 29 Apr 2022

Cited by 7 | Viewed by 2112

Abstract

Antimicrobial photodynamic therapy (aPDT) has been considered as a promising methodology to fight the multidrug resistance of pathogenic bacteria. The procedure involves a photoactive compound (photosensitizer), the red or near infrared spectrum for its activation, and an oxygen environment. In general, reactive oxygen [...] Read more.

Antimicrobial photodynamic therapy (aPDT) has been considered as a promising methodology to fight the multidrug resistance of pathogenic bacteria. The procedure involves a photoactive compound (photosensitizer), the red or near infrared spectrum for its activation, and an oxygen environment. In general, reactive oxygen species are toxic to biomolecules which feature a mechanism of photodynamic action. The present study evaluates two clinical isolates of Gram-negative Flavobacteriumhydatis (F. hydatis): a multidrug resistant (R) and a sensitive (S) strain. Both occur in farmed fish, leading to the big production losses because of the inefficacy of antibiotics. Palladium phthalocyanines (PdPcs) with methylpyridiloxy groups linked peripherally (pPdPc) or non-peripherally (nPdPc) were studied with full photodynamic inactivation for 5.0 µM nPdPc toward both F. hydatis, R and S strains (6 log), but with a half of this value (3 log) for 5.0 µM pPdPc and only for F. hydatis, S. In addition to the newly synthesized PdPcs as a “positive control” was applied a well-known highly effective zinc phthalocyanine (ZnPcMe). ZnPcMe showed optimal photocytotoxicity for inactivation of both F. hydatis R and S. The present study is encouraging for a further development of aPDT with phthalocyanines as an alternative method to antibiotic medication to keep under control the harmful pathogens in aquacultures’ farms. Full article

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13 pages, 3470 KiB

Open AccessArticle

Network Pharmacology Study to Elucidate the Key Targets of Underlying Antihistamines against COVID-19

by Ki-Kwang Oh, Md. Adnan and Dong-Ha Cho

Curr. Issues Mol. Biol. 2022, 44(4), 1597-1609; https://doi.org/10.3390/cimb44040109 - 8 Apr 2022

Cited by 6 | Viewed by 4440

Abstract

Antihistamines have potent efficacy to alleviate COVID-19 (Coronavirus disease 2019) symptoms such as anti-inflammation and as a pain reliever. However, the pharmacological mechanism(s), key target(s), and drug(s) are not documented well against COVID-19. Thus, we investigated to decipher the most significant components and [...] Read more.

Antihistamines have potent efficacy to alleviate COVID-19 (Coronavirus disease 2019) symptoms such as anti-inflammation and as a pain reliever. However, the pharmacological mechanism(s), key target(s), and drug(s) are not documented well against COVID-19. Thus, we investigated to decipher the most significant components and how its research methodology was utilized by network pharmacology. The list of 32 common antihistamines on the market were retrieved via drug browsing databases. The targets associated with the selected antihistamines and the targets that responded to COVID-19 infection were identified by the Similarity Ensemble Approach (SEA), SwissTargetPrediction (STP), and PubChem, respectively. We described bubble charts, the Pathways-Targets-Antihistamines (PTA) network, and the protein–protein interaction (PPI) network on the RPackage via STRING database. Furthermore, we utilized the AutoDock Tools software to perform molecular docking tests (MDT) on the key targets and drugs to evaluate the network pharmacological perspective. The final 15 targets were identified as core targets, indicating that Neuroactive ligand–receptor interaction might be the hub-signaling pathway of antihistamines on COVID-19 via bubble chart. The PTA network was constructed by the RPackage, which identified 7 pathways, 11 targets, and 30 drugs. In addition, GRIN2B, a key target, was identified via topological analysis of the PPI network. Finally, we observed that the GRIN2B-Loratidine complex was the most stable docking score with −7.3 kcal/mol through molecular docking test. Our results showed that Loratadine might exert as an antagonist on GRIN2B via the neuroactive ligand–receptor interaction pathway. To sum up, we elucidated the most potential antihistamine, a key target, and a key pharmacological pathway as alleviating components against COVID-19, supporting scientific evidence for further research. Full article

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16 pages, 3697 KiB

Open AccessHypothesis

Drug Investigation to Dampen the Comorbidity of Rheumatoid Arthritis and Osteoporosis via Molecular Docking Test

by Ki-Kwang Oh, Md. Adnan and Dong-Ha Cho

Curr. Issues Mol. Biol. 2022, 44(3), 1046-1061; https://doi.org/10.3390/cimb44030069 - 23 Feb 2022

Cited by 6 | Viewed by 4463

Abstract

At present, most rheumatoid arthritis (RA) patients are at risk of osteoporosis (OP), which is increased by 1.5 times compared to non-RA individuals. Hence, we investigated overlapping targets related directly to the occurrence and development of RA and OP through public databases (DisGeNET, [...] Read more.

At present, most rheumatoid arthritis (RA) patients are at risk of osteoporosis (OP), which is increased by 1.5 times compared to non-RA individuals. Hence, we investigated overlapping targets related directly to the occurrence and development of RA and OP through public databases (DisGeNET, and OMIM) and literature. A total of 678 overlapping targets were considered as comorbid factors, and 604 out of 678 were correlated with one another. Interleukin 6 (IL-6), with the highest degree of value in terms of protein–protein interaction (PPI), was considered to be a core target against comorbidity. We identified 31 existing small molecules (< 1000 g/mol) as IL-6 inhibitors, and 19 ligands were selected by the 3 primary criteria (Lipinski’s rule, TPSA, and binding energy). We postulated that MD2-TLR4-IN-1 (PubChem ID: 138454798), as confirmed by the three criteria, was the key ligand to alleviate comorbidity between RA and OP. In conclusion, we described a promising active ligand (MD2-TLR4-IN-1), and a potential target (IL-6) against comorbidity of RA and OP, providing scientific evidence for a further clinical trial. Full article

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19 pages, 7672 KiB

Open AccessArticle

An Insight into the Structural Requirements and Pharmacophore Identification of Carbonic Anhydrase Inhibitors to Combat Oxidative Stress at High Altitudes: An In-Silico Approach

by Amena Ali, Abuzer Ali, Musarrat Husain Warsi, Mohammad Akhlaquer Rahman, Mohamed Jawed Ahsan and Faizul Azam

Curr. Issues Mol. Biol. 2022, 44(3), 1027-1045; https://doi.org/10.3390/cimb44030068 - 23 Feb 2022

Cited by 7 | Viewed by 2992

Abstract

Carbonic anhydrases (CA) inhibitory action could be linked to the treatment of a number of ailments, including cancer, osteoporosis, glaucoma, and several neurological problems. For the development of effective CA inhibitors, a variety of heterocyclic rings have been investigated. Furthermore, at high altitudes, [...] Read more.

Carbonic anhydrases (CA) inhibitory action could be linked to the treatment of a number of ailments, including cancer, osteoporosis, glaucoma, and several neurological problems. For the development of effective CA inhibitors, a variety of heterocyclic rings have been investigated. Furthermore, at high altitudes, oxygen pressure drops, resulting in the formation of reactive oxygen and nitrogen species, and CA inhibitors having role in combating this oxidative stress. Acetazolamide contains thiadiazole ring, which has aroused researchers’ interest because of its CA inhibitory action. In the present study, we used a number of drug design tools, such as pharmacophore modeling, 3D QSAR, docking, and virtual screening on twenty-seven 1,3,4-thiadiazole derivatives that have been described as potential CA inhibitors in the literature. An atom-based 3D-QSAR analysis was carried out to determine the contribution of individual atoms to model generation, while a pharmacophore mapping investigation was carried out to find the common unique pharmacophoric properties required for biological activity. The coefficient of determination for both the training and test sets were statistically significant in the generated model. The best QSAR model was chosen based on the values of R² (0.8757) and Q² (0.7888). A molecular docking study was also conducted against the most potent analogue 4m, which has the highest SP docking score (−5.217) (PDB ID: 6g3v). The virtual screening revealed a number of promising compounds. The screened compound ZINC77699643 interacted with the amino acid residues, Pro201 and Thr199, in the virtual screening study (PDB ID: 6g3v). These interactions demonstrated the significance of the CA inhibitory activity of the compound. Furthermore, ADME study revealed useful information regarding compound’s drug-like properties. Therefore, the findings of the present investigation could aid in the development of more potent CA inhibitors, which could benefit the treatment of oxidative stress at high altitudes. Full article

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26 pages, 18201 KiB

Open AccessArticle

Computer-Assisted Discovery of Alkaloids with Schistosomicidal Activity

by Renata Priscila Barros de Menezes, Jéssika de Oliveira Viana, Eugene Muratov, Luciana Scotti and Marcus Tullius Scotti

Curr. Issues Mol. Biol. 2022, 44(1), 383-408; https://doi.org/10.3390/cimb44010028 - 15 Jan 2022

Cited by 10 | Viewed by 4190

Abstract

Schistosomiasis is a chronic parasitic disease caused by trematodes of the genus Schistosoma; it is commonly caused by Schistosoma mansoni, which is transmitted by Bioamphalaria snails. Studies show that more than 200 million people are infected and that more than 90% [...] Read more.

Schistosomiasis is a chronic parasitic disease caused by trematodes of the genus Schistosoma; it is commonly caused by Schistosoma mansoni, which is transmitted by Bioamphalaria snails. Studies show that more than 200 million people are infected and that more than 90% of them live in Africa. Treatment with praziquantel has the best cost–benefit result on the market. However, hypersensitivity, allergy, and drug resistance are frequently presented after administration. From this perspective, ligand-based and structure-based virtual screening (VS) techniques were combined to select potentially active alkaloids against S. mansoni from an internal dataset (SistematX). A set of molecules with known activity against S. mansoni was selected from the ChEMBL database to create two different models with accuracy greater than 84%, enabling ligand-based VS of the alkaloid bank. Subsequently, structure-based VS was performed through molecular docking using four targets of the parasite. Finally, five consensus hits (i.e., five alkaloids with schistosomicidal potential), were selected. In addition, in silico evaluations of the metabolism, toxicity, and drug-like profile of these five selected alkaloids were carried out. Two of them, namely, 11,12-methylethylenedioxypropoxy and methyl-3-oxo-12-methoxy-n(1)-decarbomethoxy-14,15-didehydrochanofruticosinate, had plausible toxicity, metabolomics, and toxicity profiles. These two alkaloids could serve as starting points for the development of new schistosomicidal compounds based on natural products. Full article

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2021

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13 pages, 2341 KiB

Open AccessArticle

Application of a Combined Peptidomics and In Silico Approach for the Identification of Novel Dipeptidyl Peptidase-IV-Inhibitory Peptides in In Vitro Digested Pinto Bean Protein Extract

by Serena Martini, Alice Cattivelli, Angela Conte and Davide Tagliazucchi

Curr. Issues Mol. Biol. 2022, 44(1), 139-151; https://doi.org/10.3390/cimb44010011 - 28 Dec 2021

Cited by 6 | Viewed by 2686

Abstract

The conventional approach in bioactive peptides discovery, which includes extensive bioassay-guided fractionation and purification processes, is tedious, time-consuming and not always successful. The recently developed bioinformatics-driven in silico approach is rapid and cost-effective; however, it lacks an actual physiological significance. In this study [...] Read more.

The conventional approach in bioactive peptides discovery, which includes extensive bioassay-guided fractionation and purification processes, is tedious, time-consuming and not always successful. The recently developed bioinformatics-driven in silico approach is rapid and cost-effective; however, it lacks an actual physiological significance. In this study a new integrated peptidomics and in silico method, which combines the advantages of the conventional and in silico approaches by using the pool of peptides identified in a food hydrolysate as the starting point for subsequent application of selected bioinformatics tools, has been developed. Pinto bean protein extract was in vitro digested and peptides were identified by peptidomics. The pool of obtained peptides was screened by in silico analysis and structure–activity relationship modelling. Three peptides (SIPR, SAPI and FVPH) were selected as potential inhibitors of the dipeptidyl-peptidase-IV (DPP-IV) enzyme by this integrated approach. In vitro bioactivity assay showed that all three peptides were able to inhibit DPP-IV with the tetra-peptide SAPI showing the highest activity (IC50 = 57.7 μmol/L). Indeed, a new possible characteristic of peptides (i.e., the presence of an S residue at the N-terminus) able to inhibit DPP-IV was proposed. Full article

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11 pages, 1667 KiB

Open AccessArticle

RETRACTED: Efficacy of Vanadyl Sulfate and Selenium Tetrachloride as Anti-Diabetic Agents against Hyperglycemia and Oxidative Stress Induced by Diabetes Mellitus in Male Rats

by Fawziah A. Al-Salmi and Reham Z. Hamza

Curr. Issues Mol. Biol. 2022, 44(1), 94-104; https://doi.org/10.3390/cimb44010007 - 24 Dec 2021

Cited by 13 | Viewed by 4162 | Retraction

Abstract

The use of metals in medicine has grown in popularity in clinical and commercial settings. In this study, the immune-protecting effects and the hypoglycemic and antioxidant activity of vanadyl sulfate (VOSO₄) and/or selenium tetrachloride (Se) on oxidative injury, DNA damage, insulin [...] Read more.

The use of metals in medicine has grown in popularity in clinical and commercial settings. In this study, the immune-protecting effects and the hypoglycemic and antioxidant activity of vanadyl sulfate (VOSO₄) and/or selenium tetrachloride (Se) on oxidative injury, DNA damage, insulin resistance, and hyperglycemia were assessed. Fifty male albino rats were divided into five groups, and all treatments were administrated at 9:00 a.m. daily for 60 successive days: control, STZ (Streptozotocin; 50 mg/kg of STZ was given to 6 h fasted animals in a single dose, followed by confirmation of diabetic state occurrence after 72 h by blood glucose estimation at >280 mg/dl), STZ (Diabetic) plus administration of VOSO₄ (15 mg/kg) for 60 days, STZ (Diabetic) plus administration of selenium tetrachloride (0.87 mg/Kg), and STZ plus VOSO₄ and, after 1/2 h, administration of selenium tetrachloride at the above doses. The test subjects’ blood glucose, insulin hormone, HbA1C, C-peptide, antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, myeloperoxidase, and xanthine oxidase), markers of lipid peroxidation (MDA), and histological sections of pancreatic tissues were evaluated, and a comet assay was performed. Histological sections in pancreas tissues were treated as indicators of both VOSO₄ and selenium tetrachloride efficacy, either alone or combined, for the alleviation of STZ toxicity. The genotoxicity of diabetes mellitus was assessed, and the possible therapeutic roles of VOSO₄ or selenium tetrachloride, or both, on antioxidant enzymes were studied. The findings show that the administration of VOSO₄ with selenium tetrachloride reduced oxidative stress to normal levels, lowered blood glucose levels, and elevated insulin hormone. Additionally, VOSO₄ with selenium tetrachloride had a synergistic effect and significantly decreased pancreatic genotoxicity. The data clearly show that both VOSO₄ and selenium tetrachloride inhibit pancreatic and DNA injury and improve the oxidative state in male rats, suggesting that the use of VOSO₄ with selenium tetrachloride is a promising synergistic potential ameliorative agent in the diabetic animal model. Full article

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15 pages, 2147 KiB

Open AccessReview

Protective Effect of Melatonin Administration against SARS-CoV-2 Infection: A Systematic Review

by Antonio Molina-Carballo, Rafael Palacios-López, Antonio Jerez-Calero, María Carmen Augustín-Morales, Ahmed Agil, Antonio Muñoz-Hoyos and Antonio Muñoz-Gallego

Curr. Issues Mol. Biol. 2022, 44(1), 31-45; https://doi.org/10.3390/cimb44010003 - 22 Dec 2021

Cited by 14 | Viewed by 11980

Abstract

Introduction: according to the World Health Organization (WHO), COVID-19 is an infectious disease caused by the SARS-CoV-2 virus, responsible for an increasing number of cases and deaths. From a preventive and therapeutic point of view, there are two concerns that affect institutions and [...] Read more.

Introduction: according to the World Health Organization (WHO), COVID-19 is an infectious disease caused by the SARS-CoV-2 virus, responsible for an increasing number of cases and deaths. From a preventive and therapeutic point of view, there are two concerns that affect institutions and healthcare professionals: global immunization (which is still far from being achieved) and the availability of drugs capable of preventing its consequences in the infected patient. In this sense, the role that melatonin can play is has been assessed in the recent literature. Justification and Objectives: the serious health, social and economic consequences of COVID-19 have forced an urgent search for preventive methods, such as vaccines, among others, and therapeutic methods that could be alternatives to the drugs currently used. In this sense, it must be accepted that one of the most recommended has been the administration of melatonin. The present study proposes to carry out a systematic review of its possible role in the treatment and/or prevention of COVID-19. Material and methods: a systematic review of the literature related to the prevention of COVID-19 through the administration of melatonin was carried out, following the sequence proposed by the Prisma Declaration regarding the identification and selection of documents, using the specialized health databases Trip Medical Database, Cochrane Library, PubMed, Medline Plus, BVS, Cuiden and generic databases such as Dialnet, Web of Science and Google Scholar for their retrieval. Appropriate inclusion and exclusion criteria are described for the articles assessed. The main limitation of the study has been the scarcity of works and the lack of defining a specific protocol in terms of dosage and administration schedule. Results: once the selection process was completed, and after an in-depth critical analysis, 197 papers were selected, and 40 of them were finally used. The most relevant results were: (1) melatonin prevents SARS-CoV-2 infection, (2) although much remains to be clarified, at high doses, it seems to have a coadjuvant therapeutic effect in the treatment of SARS-CoV-2 infection and (3) melatonin is effective against SARS-CoV-2 infection. Discussion: until group immunization is achieved in the population, it seems clear that we must continue to treat patients with SARS-CoV-2 infection, and, in the absence of a specific and effective antiviral therapy, it is advisable to continue researching and providing drugs that demonstrate validity based on the scientific evidence. In this regard, we believe that the available studies recommend the administration of melatonin for its anti-inflammatory, antioxidant, immunomodulatory, sleep-inducing, CD147, Mpro, p65 and MMP9 protein suppressing, nephrotoxicity-reducing and highly effective and safe effects. Conclusions: (1) melatonin has anti-inflammatory, antioxidant, immunomodulatory, and Mpro and MMP9 protein-inhibitory activity. (2) It has been shown to have a wide margin of safety. (3) The contributions reviewed make it an effective therapeutic alternative in the treatment of SARS-CoV-2 infection. (4) Further clinical trials are recommended to clearly define the administration protocol. Full article

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10 pages, 1488 KiB

Open AccessArticle

Permeability of Gemcitabine and PBPK Modeling to Assess Oral Administration

by Abigail Ferreira, Rui Lapa and Nuno Vale

Curr. Issues Mol. Biol. 2021, 43(3), 2189-2198; https://doi.org/10.3390/cimb43030153 - 7 Dec 2021

Cited by 3 | Viewed by 3934

Abstract

Gemcitabine is a nucleoside analog effective against several solid tumors. Standard treatment consists of an intravenous infusion over 30 min. This is an invasive, uncomfortable and often painful method, involving recurring visits to the hospital and costs associated with medical staff and equipment. [...] Read more.

Gemcitabine is a nucleoside analog effective against several solid tumors. Standard treatment consists of an intravenous infusion over 30 min. This is an invasive, uncomfortable and often painful method, involving recurring visits to the hospital and costs associated with medical staff and equipment. Gemcitabine’s activity is significantly limited by numerous factors, including metabolic inactivation, rapid systemic clearance of gemcitabine and transporter deficiency-associated resistance. As such, there have been research efforts to improve gemcitabine-based therapy efficacy, as well as strategies to enhance its oral bioavailability. In this work, gemcitabine in vitro and clinical data were analyzed and in silico tools were used to study the pharmacokinetics of gemcitabine after oral administration following different regimens. Several physiologically based pharmacokinetic (PBPK) models were developed using simulation software GastroPlus™, predicting the PK parameters and plasma concentration–time profiles. The integrative biomedical data analyses presented here are promising, with some regimens of oral administration reaching higher AUC in comparison to the traditional IV infusion, supporting this route of administration as a viable alternative to IV infusions. This study further contributes to personalized health care based on potential new formulations for oral administration of gemcitabine, as well nanotechnology-based drug delivery systems. Full article

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