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Pharmaceuticals, Volume 17, Issue 9 (September 2024) – 32 articles

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15 pages, 2881 KiB  
Article
Antidiabetic and Anti-Inflammatory Effect of Cinnamomum cassia Oil in Alloxan-Induced Diabetic Rats
by Paula Cordero-Pérez, Flor Edith Hernández-Cruz, Daniel Garza-Guzmán, Diana Patricia Moreno-Peña, Concepción Sánchez-Martínez, Liliana Torres-González, Linda E. Muñoz-Espinosa, Homero Zapata-Chavira, Idalia Cura-Esquivel, Marisol Idalí Serrano-Sandoval and Diana Raquel Rodríguez-Rodríguez
Pharmaceuticals 2024, 17(9), 1135; https://doi.org/10.3390/ph17091135 (registering DOI) - 29 Aug 2024
Abstract
Diabetes mellitus presents a great diversity of treatments that cause adverse effects; therefore, plants are a source of compounds that may have fewer adverse effects; Cinnamomum cassia (C. cassia) has compounds with potential antidiabetic activity. The objective was to evaluate the [...] Read more.
Diabetes mellitus presents a great diversity of treatments that cause adverse effects; therefore, plants are a source of compounds that may have fewer adverse effects; Cinnamomum cassia (C. cassia) has compounds with potential antidiabetic activity. The objective was to evaluate the antidiabetic effect of C. cassia oil (CCO) and its impact on oxidative stress in Wistar rats. Five groups were evaluated: (1) sham (SH), (2) 300 mg/kg CCO (CCO), (3) diabetic (D) induced with alloxan, (4) D + 300 mg/kg of CCO (D + CCO), and (5) D + 500 mg/kg of metformin (D + MET); all were treated for 5 days. CCO did not show alteration in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) vs. SH. D + CCO vs. D significantly reduced glucose (333 ± 109 vs. 458 ± 81 mg/dL), ALT (66 ± 15 vs. 160 ± 54 U/L), AST (119 ± 26 vs. 243 ± 104 U/L), and blood urea nitrogen (18.8 ± 2.3 vs. 29.2 ± 6.9 mg/dL). No significant changes were observed in D + CCO vs. D in malondialdehyde (MDA), reduced glutathione (GSH), and superoxide dismutase (SOD), whereas a significant reduction in MDA and GSH was achieved in D + MET, with an increase in SOD. There was a reduction in Rela and Gpx in D + CCO and D + MET vs. D. CCO has antidiabetic and anti-inflammatory effects and reduces ALT, AST, and BUN levels. Full article
(This article belongs to the Special Issue Discovery of Natural Products as Potential Antidiabetic Agents)
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30 pages, 27271 KiB  
Review
A Comprehensive Review of Silver and Gold Nanoparticles as Effective Antibacterial Agents
by Ricardo Aguilar-Garay, Luis F. Lara-Ortiz, Maximiliano Campos-López, Dafne E. Gonzalez-Rodriguez, Margoth M. Gamboa-Lugo, Jorge A. Mendoza-Pérez, Álvaro Anzueto-Ríos and Dulce E. Nicolás-Álvarez
Pharmaceuticals 2024, 17(9), 1134; https://doi.org/10.3390/ph17091134 (registering DOI) - 29 Aug 2024
Abstract
The increasing threat from antibiotic-resistant bacteria has necessitated the development of novel methods to counter bacterial infections. In this context, the application of metallic nanoparticles (NPs), especially gold (Au) and silver (Ag), has emerged as a promising strategy due to their remarkable antibacterial [...] Read more.
The increasing threat from antibiotic-resistant bacteria has necessitated the development of novel methods to counter bacterial infections. In this context, the application of metallic nanoparticles (NPs), especially gold (Au) and silver (Ag), has emerged as a promising strategy due to their remarkable antibacterial properties. This review examines research published between 2006 and 2023, focusing on leading journals in nanotechnology, materials science, and biomedical research. The primary applications explored are the efficacy of Ag and Au NPs as antibacterial agents, their synthesis methods, morphological properties, and mechanisms of action. An extensive review of the literature on NPs synthesis, morphology, minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and effectiveness against various Gram(+/−) bacteria confirms the antibacterial efficacy of Au and Ag NPs. The synthesis methods and characteristics of NPs, such as size, shape, and surface charge, are crucial in determining their antibacterial activity, as these factors influence their interactions with bacterial cells. Furthermore, this review underscores the urgent necessity of standardizing synthesis techniques, MICs, and reporting protocols to enhance the comparability and reproducibility of future studies. Standardization is essential for ensuring the reliability of research findings and accelerating the clinical application of NP-based antimicrobial approaches. This review aims to propel NP-based antimicrobial strategies by elucidating the properties that enhance the antibacterial activity of Ag and Au NPs. By highlighting their inhibitory effects against various bacterial strains and relatively low cytotoxicity, this work positions Ag and Au NPs as promising materials for developing antibacterial agents, making a significant contribution to global efforts to combat antibiotic-resistant pathogens. Full article
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19 pages, 2863 KiB  
Article
Anticancer Activity of Imidazolyl Gold(I/III) Compounds in Non-Small Cell Lung Cancer Cell Lines
by Rossana Galassi, Nicola Sargentoni, Sofia Renzi, Lorenzo Luciani, Caterina Bartolacci, Prasad Pattabhi, Cristina Andreani and Stefania Pucciarelli
Pharmaceuticals 2024, 17(9), 1133; https://doi.org/10.3390/ph17091133 - 28 Aug 2024
Abstract
Lung cancer is a leading cause of cancer-related death worldwide that needs updated therapies to contrast both the serious side effects and the occurrence of drug resistance. A panel of non-small cell lung cancer (NSCLC) cells were herein employed as cancer models. Eight [...] Read more.
Lung cancer is a leading cause of cancer-related death worldwide that needs updated therapies to contrast both the serious side effects and the occurrence of drug resistance. A panel of non-small cell lung cancer (NSCLC) cells were herein employed as cancer models. Eight structurally related gold(I) and gold(III) complexes with NHC and halides or triphenylphosphane ligands were investigated as lung cancer cell growth inhibitors. As expected, gold compounds with PPh3 were found to be more cytotoxic than homoleptic [(NHC)2-Au(I)]X or heteroleptic NHC-Au(I)X or NHC-Au(III)X3 complexes. Mixed ligand gold(I) compounds exhibiting the linear NHC-AuPPh3 (compound 7) or the trigonal NHC-Au(Cl)PPh3 (compound 8) arrangements at the central metal were found to be the best lung cancer cytotoxic compounds. Analysis of the TrxR residual activity of the treated cells revealed that these compounds efficiently inhibit the most accredited molecular target for gold compounds, the TrxR, with compound 8 reaching more than 80% activity reduction in lung cells. Some of the current cancer lung therapy protocols consist of specific lung cancer cell cytotoxic agents combined with antifolate drugs; interestingly, the herein gold compounds are both TrxR and antifolate inhibitors. The human DHFR was inhibited with IC50 ranging between 10–21 µM, depending on substrate concentrations, proceeding by a likely allosteric mechanism only for compound 8. Full article
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16 pages, 35907 KiB  
Article
The Cardioprotective Potential of Herbal Formulas in Myocardial Infarction-Induced Heart Failure through Inhibition of JAK/STAT3 Signaling and Improvement of Cardiac Function
by Youn-Jae Jang, Hye-Yoom Kim, Se-Won Na, Mi-Hyeon Hong, Jung-Joo Yoon, Ho-Sub Lee and Dae-Gill Kang
Pharmaceuticals 2024, 17(9), 1132; https://doi.org/10.3390/ph17091132 - 27 Aug 2024
Viewed by 185
Abstract
Myocardial infarction (MI) is a leading cause of heart failure, characterized by adverse cardiac remodeling. This study evaluated the cardioprotective potential of Dohongsamul-tang (DHT), a traditional Korean herbal formula, in a rat model of MI-induced heart failure. Rats underwent left anterior descending (LAD) [...] Read more.
Myocardial infarction (MI) is a leading cause of heart failure, characterized by adverse cardiac remodeling. This study evaluated the cardioprotective potential of Dohongsamul-tang (DHT), a traditional Korean herbal formula, in a rat model of MI-induced heart failure. Rats underwent left anterior descending (LAD) artery ligation and were treated with either 100 mg/kg or 200 mg/kg of DHT daily for 8 weeks. DHT treatment significantly improved cardiac function, as evidenced by increased ejection fraction (EF) from 62.1% to 70.1% (100 mg/kg) and fractional shortening (FS) from 32.3% to 39.4% (200 mg/kg) compared to the MI control group. Additionally, DHT reduced infarct size by approximately 63.3% (from 60.0% to 22.0%) and heart weight by approximately 16.7% (from 3.6 mg/g to 3.0 mg/g), and significantly decreased levels of heart failure biomarkers: LDH was reduced by 37.6% (from 1409.1 U/L to 879.1 U/L) and CK-MB by 47.6% (from 367.3 U/L to 192.5 U/L). Histological analysis revealed a reduction in left ventricle (LV) fibrosis by approximately 50% (from 24.0% to 12.0%). At the molecular level, DHT inhibited the expression of phospho-JAK by 75% (from 2-fold to 0.5-fold), phospho-STAT3 by 30.8% (from 1.3-fold to 0.9-fold), Bax/Bcl-2 by 56.3% (from 3.2-fold to 1.4-fold), and caspase-3 by 46.3% (from 1.23-fold to 0.66-fold). These results suggest that DHT exerts cardioprotective effects by modulating the JAK/STAT3 signaling pathway, highlighting its potential as a therapeutic option for heart failure. Full article
(This article belongs to the Special Issue Plant-Based Therapies for Circulatory Disorders)
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14 pages, 3821 KiB  
Article
Enhanced Anti-Obesity Effects of Euphorbia Kansui Extract through Macrophage and Gut Microbiota Modulation: A Real-World Clinical and In Vivo Study
by Ji-Won Noh, Jung-Hwa Yoo and Byung-Cheol Lee
Pharmaceuticals 2024, 17(9), 1131; https://doi.org/10.3390/ph17091131 - 27 Aug 2024
Viewed by 192
Abstract
Rising obesity and associated multi-systemic complications amplify the health burden. Euphorbia kansui (EK) extract is clinically recognized for managing obesity. In a human study, 240 obese individuals were categorized into two cohorts: those receiving solely herbal medicine (HM group) and those administered EK [...] Read more.
Rising obesity and associated multi-systemic complications amplify the health burden. Euphorbia kansui (EK) extract is clinically recognized for managing obesity. In a human study, 240 obese individuals were categorized into two cohorts: those receiving solely herbal medicine (HM group) and those administered EK concomitantly with herbal medicine (EK group). An in vivo examination using C57BL/6-Lepob/Lepob mice elucidated mechanisms involving macrophages and gut microbiota with associated metabolic advantages. The clinical study revealed a significant 7.22% body weight reduction during 91.55 average treatment days and examined 16.71% weight loss at 300 days after treatment. In whole subjects, 60.4%, 21.3%, and 6.3% achieved weight reductions exceeding 5%, 10%, and 15%, respectively. Impressively, the EK group exhibited superior weight loss compared to the HM group (EK: −7.73% vs. HM: −6.27%, p = 0.012). The anti-obesity effect was positively associated with EK therapy frequency and herbal medicine duration. In the in vivo study, EK significantly improved insulin sensitivity and mitigated infiltration of adipose tissue macrophages (ATMs) by modulating the CD11c+ and CD206+ subtypes. EK also correlated with increased Bacteroidetes and Firmicutes populations and reduced Proteobacteria and Verrucomicrobia. Consequently, EK is an effective adjunctive anti-obesity therapy offering metabolic benefits by modulating ATMs and gut microbiota profiles. Full article
(This article belongs to the Special Issue Anti-obesity and Anti-aging Natural Products)
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15 pages, 1342 KiB  
Article
Qualitative and Quantitative Analysis of Phytochemicals in Sayeok-Tang via UPLC-Q-Orbitrap-MS and UPLC-TQ-MS/MS
by Yu Jin Kim, Seol Jang and Youn-Hwan Hwang
Pharmaceuticals 2024, 17(9), 1130; https://doi.org/10.3390/ph17091130 - 27 Aug 2024
Viewed by 192
Abstract
Sayeok-tang (SYT) is a traditional herbal formula comprising three medicinal herbs: Glycyrrhiza uralensis, Zingiber officinale, and Aconitum carmichaeli. Several studies have employed liquid chromatography-mass spectrometry (LC-MS) to qualitatively analyze the components and metabolites of SYT in vitro and in vivo; [...] Read more.
Sayeok-tang (SYT) is a traditional herbal formula comprising three medicinal herbs: Glycyrrhiza uralensis, Zingiber officinale, and Aconitum carmichaeli. Several studies have employed liquid chromatography-mass spectrometry (LC-MS) to qualitatively analyze the components and metabolites of SYT in vitro and in vivo; however, studies on quantitative analysis of SYT, which is important for quality control, are absent or limited to only a few components. In this study, ultrahigh-performance liquid chromatography coupled with quadrupole (UPLC-Q)-Orbitrap-MS was used to screen the phytochemicals of SYT, revealing a total of 42 compounds. Among them, 24 compounds were simultaneously quantified within 20 min via UPLC-TQ-MS/MS in the multiple reaction monitoring mode. The developed analytical method was validated for its linearity (r2 ≥ 0.9992), precision (0.36–2.96%), accuracy (−6.52–4.64%), and recovery (94.39–119.07%) for all analytes, exhibiting acceptable results. The validated method was applied in the analysis of SYT extracts, and the 24 compounds were quantified in the range of 0.004–6.882 mg/g (CV ≤ 3.746%). Among them, liquiritin apioside (6.870–6.933 mg/g), glycyrrhizic acid (5.418–5.540 mg/g), and liquiritin (1.303–1.331 mg/g) from G. uralensis were identified as the relatively abundant compounds. The presented validated analytical method is highly promising for the comprehensive quality control of SYT, offering fast, highly sensitive, and reliable analysis. Full article
(This article belongs to the Special Issue Advances in Mass Spectrometry Metrology in Pharmaceutical Sciences)
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44 pages, 6622 KiB  
Article
Chia Seed (Salvia hispanica) Attenuates Chemically Induced Lung Carcinomas in Rats through Suppression of Proliferation and Angiogenesis
by Naglaa A. Ali, Ghada H. Elsayed, Safaa H. Mohamed, Asmaa S. Abd Elkarim, Mohamed S. Aly, Abdelbaset M. Elgamal, Wael M. Elsayed and Samah A. El-Newary
Pharmaceuticals 2024, 17(9), 1129; https://doi.org/10.3390/ph17091129 - 27 Aug 2024
Viewed by 201
Abstract
In 2022, 2.5 million cases of lung cancer were diagnosed, resulting in 1.8 million deaths. These statistics have motivated us to introduce a new natural product which is feasible in lung cancer therapies. This comprehensive study was performed to study the effects of [...] Read more.
In 2022, 2.5 million cases of lung cancer were diagnosed, resulting in 1.8 million deaths. These statistics have motivated us to introduce a new natural product which is feasible in lung cancer therapies. This comprehensive study was performed to study the effects of chia seed extracts (70% ethanol and petroleum ether) on lung cancer in vitro and in vivo models. The invitro cytotoxicity activity of the chia extracts was studied in lung cancer cell lines (A549 cells). After 48 h, chia alcohol and ether extracts showed more inhibitory influence (IC50, 16.08, and 14.8 µg/mL, respectively) on A549 cells compared to Dox (IC50, 13.6 µg/mL). In vivo, administration of chia alcohol and ether extracts (500 mg/kg/day, orally for 20 weeks) recovered 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung cancer, as a significant reduction in the lung cancer biomarkers, including the relative weight of the lung (20.0 and 13.33%), ICAM(31.73 and 15.66%), and c-MYC (80 and 96%) and MMP9(60 and 69%) expression genes, and improvement in these changes were observed by histopathological examinations of the lung tissues compared to the lung control. Chia seeds fought lung cancer via suppression of proliferation, angiogenesis, inflammation, and activation apoptosis. These activities may be attributed to the chemical composition of chia, which is identified by LC-Mass, such as caffeic acid, vanillic acid, kaempferol-3-O-glucuronide, and taxifolin. Finally, we can conclude that chia seeds have an anti-lung cancer effect with a good safety margin. Full article
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18 pages, 5814 KiB  
Article
Mechanism Study of Xiaoyao San against Nonalcoholic Steatohepatitis-Related Liver Fibrosis Based on a Combined Strategy of Transcriptome Analysis and Network Pharmacology
by Di Yan, Xiaoling Zhang, Chengmei Ma, Wenting Huang, Mimi Hao and Lan Xie
Pharmaceuticals 2024, 17(9), 1128; https://doi.org/10.3390/ph17091128 - 27 Aug 2024
Viewed by 222
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the leading cause of liver disease worldwide. Nonalcoholic steatohepatitis (NASH) is an advanced form of NAFLD. The livers of patients with NASH are more likely to develop fibrosis. Xiaoyao San (XYS) is a classic traditional Chinese medicine [...] Read more.
Nonalcoholic fatty liver disease (NAFLD) is the leading cause of liver disease worldwide. Nonalcoholic steatohepatitis (NASH) is an advanced form of NAFLD. The livers of patients with NASH are more likely to develop fibrosis. Xiaoyao San (XYS) is a classic traditional Chinese medicine (TCM) formula that has been widely used in treating liver diseases. In this study, we elucidated the effects and mechanism of XYS in treating NASH-related liver fibrosis by combining high-throughput sequencing-based high-throughput screening with network pharmacology analysis. Our work revealed that XYS may play a role in preventing NASH-related liver fibrosis by regulating biological functions related to the extracellular matrix (ECM), inflammation, and metabolism. Additionally, Bupleuri Radix, Poria, Zingiberis Rhizoma Recens, and Paeoniae Radix Alba are the key herbs of XYS that could partially represent the functions of XYS. These regulatory effects are mediated by targeting signal transducer and activator of transcription 3 (STAT3), nuclear factor kappa B (NFκB), and peroxisome proliferator-activated receptor gamma (PPARγ) signaling. Narcissin, casuarictin, and γ-sitosterol were identified as representative active compounds in XYS targeting STAT3, NFκB, and PPARγ, respectively. Taken together, our findings provide a novel strategy for investigating the pharmacological effects and biological mechanisms of a TCM formula. Full article
(This article belongs to the Section Pharmacology)
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17 pages, 1142 KiB  
Article
The Influence of Dapagliflozin on Foot Microcirculation in Patients with Type 2 Diabetes with and without Peripheral Arterial Disease—A Pilot Study
by Božena Bradarić, Tomislav Bulum, Neva Brkljačić, Željko Mihaljević, Miroslav Benić and Božo Bradarić Lisić
Pharmaceuticals 2024, 17(9), 1127; https://doi.org/10.3390/ph17091127 - 26 Aug 2024
Viewed by 323
Abstract
The results of large cardiovascular studies indicate that SGLT-2 inhibitors may increase the risk of leg amputations. This study aims to investigate whether dapagliflozin therapy affects peripheral vascular oxygenation, i.e., microcirculation in the foot, as measured by transcutaneous oxygen pressure (TcPO2) in patients [...] Read more.
The results of large cardiovascular studies indicate that SGLT-2 inhibitors may increase the risk of leg amputations. This study aims to investigate whether dapagliflozin therapy affects peripheral vascular oxygenation, i.e., microcirculation in the foot, as measured by transcutaneous oxygen pressure (TcPO2) in patients with type 2 diabetes (T2DM) and peripheral arterial disease (PAD) compared to patients without PAD. The patients with PAD were randomized into two groups. In the first 35 patients with PAD, dapagliflozin was added to the therapy; in the other 26 patients with PAD, other antidiabetic drugs were added to the therapy. Dapagliflozin was added to the therapy in all patients without PAD. TcPO2 measurement, Ankle Brachial Index (ABI), anthropometric measurements, and laboratory tests were performed. After a follow-up period of 119.35 days, there was no statistically significant difference in the reduction of mean TcPO2 values between the group with T2DM with PAD treated with dapagliflozin and the group with T2DM with PAD treated with other antidiabetic drugs (3.88 mm Hg, SD = 15.13 vs. 1.48 mm Hg, SD = 11.55, p = 0.106). Patients with control TcPO2 findings suggestive of hypoxia (TcPO2 < 40 mm Hg) who were treated with dapagliflozin had a clinically significant decrease in mean TcPO2 of 10 mm Hg or more (15.8 mm Hg and 12.90 mm Hg). However, the aforementioned decrease in TcPO2 was not statistically significantly different from the decrease in TcPO2 in the group with PAD treated with other diabetic medications (p = 0.226, p = 0.094). Based on the available data, dapagliflozin appears to affect tissue oxygenation in T2DM with PAD. However, studies with a larger number of patients and a longer follow-up period are needed to determine the extent and significance of this effect. Full article
(This article belongs to the Special Issue Advancements in Cardiovascular and Antidiabetic Drug Therapy)
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23 pages, 5117 KiB  
Article
Production and Antibacterial Activity of Atypical Siderophore from Pseudomonas sp. QCS59 Recovered from Harpachene schimperi
by Mashael A. Almuhawish, Essam Kotb, Eida Alkhaldi and Asmaa A. Ahmed
Pharmaceuticals 2024, 17(9), 1126; https://doi.org/10.3390/ph17091126 - 26 Aug 2024
Viewed by 239
Abstract
Among sixty-eight pseudomonads, isolate QCS59 from the rhizosphere of H. schimperi was selected based on its siderophore level. Production was optimal in Kings B supplemented with 2% peptone and 0.5% fructose at pH 6.5 and 25 °C for 72 h. Additionally, the threshold [...] Read more.
Among sixty-eight pseudomonads, isolate QCS59 from the rhizosphere of H. schimperi was selected based on its siderophore level. Production was optimal in Kings B supplemented with 2% peptone and 0.5% fructose at pH 6.5 and 25 °C for 72 h. Additionally, the threshold potential of iron was found at a concentration of 10 µM. After purification, the acidified siderophore presented a maximum absorption peak of 360 nm, while the neutral form presented a maximum of 414 nm, confirming its pyoverdine (PVD) nature. Furthermore, a major peak appeared at a retention time (RT) of 27.5 min during RP-HPLC, confirming its homogeneity. Interestingly, it demonstrated effective antibacterial activity, especially against Escherichia coli ATCC 8739, with a minimum inhibitory concentration (MIC) of 6.3 µg/mL and a minimum bactericidal concentration (MBC) of 12.5 µg/mL. At ½ the MIC value, it inhibited 82.1% of well-established biofilms of Salmonella enterica. There was an increase in malondialdehyde (MDA) and antioxidative enzymes, especially catalase (CAT) in the treated bacteria because of the peroxidation of membrane lipids and oxidative stress, respectively. SEM proved cellular lysis and surface malformation in most of the treated bacteria. This study concludes that QCS59 siderophore is a promising antibacterial candidate for treating wastewater bacteria and skin pathogens. Full article
(This article belongs to the Section Biopharmaceuticals)
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9 pages, 1641 KiB  
Systematic Review
Dexmedetomidine as Adjunctive Therapy for the Treatment of Alcohol Withdrawal Syndrome: A Systematic Review and Meta-Analysis
by Marco Fiore, Aniello Alfieri, Giacomo Torretta, Maria Beatrice Passavanti, Pasquale Sansone, Vincenzo Pota, Vittorio Simeon, Paolo Chiodini, Antonio Corrente and Maria Caterina Pace
Pharmaceuticals 2024, 17(9), 1125; https://doi.org/10.3390/ph17091125 - 26 Aug 2024
Viewed by 390
Abstract
Alcohol withdrawal syndrome (AWS) is defined as the cessation or reduction in heavy and prolonged alcohol use within several hours to a few days of cessation. The recommended first-line therapy for AWS ranging from mild to severe or complicated remains benzodiazepines; in cases [...] Read more.
Alcohol withdrawal syndrome (AWS) is defined as the cessation or reduction in heavy and prolonged alcohol use within several hours to a few days of cessation. The recommended first-line therapy for AWS ranging from mild to severe or complicated remains benzodiazepines; in cases where benzodiazepines are not adequate in controlling persistent autonomic hyperactivity or anxiety, dexmedetomidine could be utilized. The possible advantage of dexmedetomidine compared to benzodiazepines is that it does not cause respiratory depression, thus reducing the risk of intubation and hospitalization in the ICUs, with the potential reduction in healthcare costs. The purpose of this systematic review and meta-analysis (PROSPERO CRD42018084370) is to evaluate the effectiveness and safety of dexmedetomidine as adjunctive therapy to the standard of care for the treatment of AWS. We retrieved literature from PubMed, EMBASE, and CENTRAL until 10 January 2024. Eligible studies were both randomized trials and nonrandomised studies with a control group, published in the English language and peer-reviewed journals. The primary outcome was tracheal intubation; secondary outcomes were (i) bradycardia and (ii) hypotension. A total of 3585 papers were retrieved: 2635 from EMBASE, 930 from Medline, and 20 from CENTRAL. After eliminating duplicates, 2960 papers were screened by title and abstract; 75 out of the 2960 papers were read in full text. The qualitative synthesis included nine of all manuscripts read in full text. The quantitative synthesis included eight studies for the primary outcome (tracheal intubation), seven for the secondary outcome bradycardia, and six for the secondary outcome hypotension. The meta-analysis showed that Dexmedetomidine, as adjunctive therapy, is not more effective than standard therapy in reducing the risk of tracheal intubation in AWS [RR: 0.57, 95% CI: 0.25–1.3, p = 0.15]. It also appears to be less safe than sedative therapy as it significantly increases the risk of bradycardia [RR: 2.68, 95% CI: 1.79–4.16, p = 0.0016]. Hypotension was not significantly different in patients who received dexmedetomidine [RR: 1.5, 95% CI: 0.69–3.49, p = 0.21]. Full article
(This article belongs to the Section Pharmacology)
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12 pages, 3431 KiB  
Article
Cu2O Nanoparticles as Nanocarriers and Its Antibacterial Efficacy
by María Isabel Torres-Ramos, Ubaldo de Jesús Martín-Camacho, Jorge Alberto Sánchez-Burgos, Suresh Ghotekar, Oscar Arturo González-Vargas, Mamoun Fellah and Alejandro Pérez-Larios
Pharmaceuticals 2024, 17(9), 1124; https://doi.org/10.3390/ph17091124 - 26 Aug 2024
Viewed by 436
Abstract
In this study, Cu2O nanoparticles were synthesized using the sol–gel technique and subsequently functionalized with extracts from plants of the Rauvolfioideae subfamily and citrus fruits. Comprehensive characterization techniques, including UV-Vis spectroscopy, FT-IR, XRD, BET, SEM, and TEM, were employed to evaluate [...] Read more.
In this study, Cu2O nanoparticles were synthesized using the sol–gel technique and subsequently functionalized with extracts from plants of the Rauvolfioideae subfamily and citrus fruits. Comprehensive characterization techniques, including UV-Vis spectroscopy, FT-IR, XRD, BET, SEM, and TEM, were employed to evaluate the structural and surface properties of the synthesized nanoparticles. The results demonstrated that both functionalized Cu2O nanoparticles exhibit mesoporous structures, as confirmed by nitrogen adsorption–desorption isotherms and the pore size distribution analysis. The green extract functionalized nanoparticles displayed a more uniform pore size distribution compared to those functionalized with the orange extract. The study underscores the potential of these functionalized Cu2O nanoparticles for applications in drug delivery, catalysis, and adsorption processes, highlighting the influence of the functionalization method on their textural properties and performance in antibacterial efficacy. Full article
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25 pages, 6006 KiB  
Article
Thiophene-Linked 1,2,4-Triazoles: Synthesis, Structural Insights and Antimicrobial and Chemotherapeutic Profiles
by Nada A. El-Emam, Mahmoud B. El-Ashmawy, Ahmed A. B. Mohamed, El-Sayed E. Habib, Subbiah Thamotharan, Mohammed S. M. Abdelbaky, Santiago Garcia-Granda and Mohamed A. A. Moustafa
Pharmaceuticals 2024, 17(9), 1123; https://doi.org/10.3390/ph17091123 - 25 Aug 2024
Viewed by 395
Abstract
The reaction of thiophene-2-carbohydrazide 1 or 5-bromothiophene-2-carbohydrazide 2 with various haloaryl isothiocyanates and subsequent cyclization by heating in aqueous sodium hydroxide yielded the corresponding 4-haloaryl-5-(thiophen-2-yl or 5-bromothiophen-2-yl)-2,4-dihydro-3H-1,2,4-triazole-3-thione 5a-e. The triazole derivatives 5a and 5b were reacted with different [...] Read more.
The reaction of thiophene-2-carbohydrazide 1 or 5-bromothiophene-2-carbohydrazide 2 with various haloaryl isothiocyanates and subsequent cyclization by heating in aqueous sodium hydroxide yielded the corresponding 4-haloaryl-5-(thiophen-2-yl or 5-bromothiophen-2-yl)-2,4-dihydro-3H-1,2,4-triazole-3-thione 5a-e. The triazole derivatives 5a and 5b were reacted with different secondary amines and formaldehyde solution to yield the corresponding 2-aminomethyl-4-haloaryl-2,4-dihydro-3H-1,2,4-triazole-3-thiones 6ae, 7ae, 8, 9, 10a and 10b in good yields. The in vitro antimicrobial activity of compounds 5ae, 6ae, 7ad, 8, 9, 10a and 10b was evaluated against a panel of standard pathogenic bacterial and fungal strains. Compounds 5a, 5b, 5e, 5f, 6ae, 7ad, 8, 9, 10a and 10b showed marked activity, particularly against the tested Gram-positive bacteria and the Gram-negative bacteria Escherichia coli, and all the tested compounds were almost inactive against all the tested fungal strains. In addition, compounds 5e, 6ae, 7ad and 10a exhibited potent anti-proliferative activity, particularly against HepG-2 and MCF-7 cancer cell lines (IC50 < 25 μM). A detailed structural insight study based on the single crystals of compounds 5a, 5b, 6a, 6d and 10a is also reported. Molecular docking studies of the highly active antibacterial compounds 5e, 6b, 6d, 7a and 7d showed a high affinity for DNA gyrase. Meanwhile, the potent anti-proliferative activity of compounds 6d, 6e and 7d may be attributed to their high affinity for cyclin-dependent kinase 2 (CDK2). Full article
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3 pages, 177 KiB  
Editorial
Antibiotic Resistance in Gram-Negative Bacteria: The Threat from the Pink Corner
by Alfizah Hanafiah and Bruno S. Lopes
Pharmaceuticals 2024, 17(9), 1122; https://doi.org/10.3390/ph17091122 - 25 Aug 2024
Viewed by 394
Abstract
Antibiotic resistance in Gram-negative bacteria is a formidable challenge in modern medicine [...] Full article
14 pages, 517 KiB  
Review
A New Medical Evaluation for Gastric Cancer Patients to Increase the Success Rate of Immunotherapy: A 2024 Update
by Gabriel Samasca, Claudia Burz, Irena Pintea, Adriana Muntean, Diana Deleanu, Iulia Lupan and Vasile Bintintan
Pharmaceuticals 2024, 17(9), 1121; https://doi.org/10.3390/ph17091121 - 24 Aug 2024
Viewed by 430
Abstract
Researchers have performed numerous studies on immunotherapy because of the high death rate associated with gastric cancer (GC). GC immunotherapy research has made tremendous progress, and we wanted to provide an update on this topic. On the basis of this update, we suggest [...] Read more.
Researchers have performed numerous studies on immunotherapy because of the high death rate associated with gastric cancer (GC). GC immunotherapy research has made tremendous progress, and we wanted to provide an update on this topic. On the basis of this update, we suggest performing a new medical evaluation before initiating immunotherapy in patients with GC to increase the success rate of immunotherapies. We propose that before patients start GC immunotherapy, they should be evaluated and given a score of one to two points for the following factors: immunopathological features, molecular and genomic features, potential consequences for bacterial pathogens, potential immunotherapeutic resistance and hyperprogressive illness, and the potential to use biomarkers to gauge their prognosis and immunotherapy responses to optimize immunotherapy following surgery. The proposed scoring system could also help in the diagnosis of GC. With all the advances in genetics, immunology, and microbiology, the diagnosis of GC could be improved, not changed. Currently, patients diagnosed with GC undergo surgical resection as the only permanent solution. Patients who meet the maximum score from the presented proposal could be eligible immediately after diagnosis for immunotherapy. Therefore, immunotherapy could be a first-line option for clinicians. Full article
(This article belongs to the Special Issue Pharmacotherapy of Gastric Cancer)
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23 pages, 7398 KiB  
Article
Computational Design and Optimization of Peptide Inhibitors for SIRT2
by Heba A. Alkhatabi, Fatmah M. A. Naemi, Reem Alsolami and Hisham N. Alatyb
Pharmaceuticals 2024, 17(9), 1120; https://doi.org/10.3390/ph17091120 - 24 Aug 2024
Viewed by 392
Abstract
Sirtuin 2 (SIRT2), an NAD+-dependent deacetylase, is crucial for regulating vital physiological processes, including aging, DNA repair, and cell cycle progression. Its abnormal activity is linked to diseases such as Parkinson’s disease, cancer, and metabolic disorders, making it a potential target for therapeutic [...] Read more.
Sirtuin 2 (SIRT2), an NAD+-dependent deacetylase, is crucial for regulating vital physiological processes, including aging, DNA repair, and cell cycle progression. Its abnormal activity is linked to diseases such as Parkinson’s disease, cancer, and metabolic disorders, making it a potential target for therapeutic intervention. While small molecule inhibitors have been studied, peptide-based inhibitors offer a promising alternative due to their selectivity and bioavailability. This study explores the effects of converting the naturally occurring cyclic inhibitor peptide of SIRT2 (S2iL5) into a non-cyclic form by replacing a residue with FAK (LYS + CF3CO). The new peptide sequence, Tyr-His-Thr-Tyr-His-Val-FAK (LYS)-Arg-Arg-Thr-Asn-Tyr-Tyr-Cys, was modeled to confirm its stable conformation. Docking studies and MM/GBSA calculations showed that the non-cyclic peptide had a better binding free energy (−50.66 kcal/mol) compared to the cyclic S2iL5 (−49.44 kcal/mol). Further mutations generated 160,000 unique peptides, screened using a machine learning-based QSAR model. Three promising peptides (Peptide 1: YGGNNVKRRTNYYC, Peptide 2: YMGEWVKRRTNYYC, and Peptide 3: YGGNGVKRRTNYYC) were selected and further modeled. Molecular dynamics (MD) analyses demonstrated that Peptide 1 and Peptide 2 had significant potential as SIRT2 inhibitors, showing moderate stability and some structural flexibility. Their best binding free energies were −59.07 kcal/mol and −46.01 kcal/mol, respectively. The study aimed to enhance peptide flexibility and binding affinity, suggesting that optimized peptide-based inhibitors can interact effectively with SIRT2. However, further experimental validation is necessary to confirm these computational predictions and evaluate the therapeutic potential of the identified peptides. Full article
(This article belongs to the Special Issue Computer-Aided Drug Design and Drug Discovery)
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26 pages, 1726 KiB  
Review
Applications of Capillary Electrophoresis for the Detection of Adulterants in Dietary Supplements
by Gabriel Hancu, Blanka Székely-Szentmiklósi, Denisa Gabriela Stroia and Hajnal Kelemen
Pharmaceuticals 2024, 17(9), 1119; https://doi.org/10.3390/ph17091119 - 24 Aug 2024
Viewed by 342
Abstract
In recent years, the consumption of dietary supplements, particularly those incorporating plant-based ingredients, has increased greatly, driven by the perception of their natural origins and purported minimal health risks. However, one significant safety concern revolves around the adulteration of dietary supplements, wherein unscrupulous [...] Read more.
In recent years, the consumption of dietary supplements, particularly those incorporating plant-based ingredients, has increased greatly, driven by the perception of their natural origins and purported minimal health risks. However, one significant safety concern revolves around the adulteration of dietary supplements, wherein unscrupulous manufacturers may illegally incorporate pharmaceutical substances or their analogs into these products to achieve increased efficiency and bolster sales. This review assesses the role of capillary electrophoresis (CE) in ensuring the quality control of dietary supplement products over the past two decades. This study provides an overview of various applications of CE in analyzing dietary supplements, outlining the typical attributes of natural product analysis using CE. These analyses demonstrate the broad versatility of CE, exemplified by its diverse applications and detection modes. Moreover, the review highlights the growing prominence of CE as a separation technique in quality control, by comparison with more conventional methods like high-performance liquid chromatography (HPLC). Through this exploration, the review elucidates the pivotal role of CE in upholding the integrity and safety of dietary supplements, in connection with a landscape of evolving regulatory challenges and consumer demands. Full article
(This article belongs to the Special Issue Analytical Techniques in the Pharmaceutical Sciences 2023)
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14 pages, 4738 KiB  
Article
The Role of ADCY1 in Regulating the Sensitivity of Platinum-Based Chemotherapy in NSCLC
by Ting Zou, Jun-Yan Liu, Zhao-Qian Liu, Di Xiao and Juan Chen
Pharmaceuticals 2024, 17(9), 1118; https://doi.org/10.3390/ph17091118 - 24 Aug 2024
Viewed by 352
Abstract
Lung cancer has the highest fatality rate among malignant tumors in the world. Finding new biomarkers of drug resistance is of great importance in the prognosis of lung cancer patients. We found that the polymorphisms of Adenylate Cyclase 1 (ADCY1) are significantly associated [...] Read more.
Lung cancer has the highest fatality rate among malignant tumors in the world. Finding new biomarkers of drug resistance is of great importance in the prognosis of lung cancer patients. We found that the polymorphisms of Adenylate Cyclase 1 (ADCY1) are significantly associated with platinum-based chemotherapy resistance in lung cancer patients in our previous research. In this study, we wanted to identify the mechanism of ADCY1 affecting platinum resistance. We used an MTT assay to find if the expression of ADCY1 is associated with the sensitivity of cisplatin in A549, H1299, and A549-DDP cells. Then, we performed CCK-8 tests to detect the absorbance of these cells stimulated by ADCY1, which can discover the cell proliferation that is affected by ADCY1. We investigated cell apoptosis and cell cycles regulated by ADCY1 through the flow cytometry assay. RNA sequencing was used to find the downstream genes affected by ADCY1 which may be associated with drug resistance in lung cancer patients. ADCY1 has higher expression in lung cancer cells than in normal cells. ADCY1 can affect cisplatin resistance in lung cancer cells by regulating cell proliferation, cell apoptosis, and the cell cycle. It may control cell apoptosis by regulating the classical apoptosis biomarkers Bax and Bcl2. Our study showed that ADCY1 may be a new biomarker in the prognosis of lung cancer patients. Much work remains to be carried out to clarify the mechanism in this important emerging field. Full article
(This article belongs to the Special Issue Adjuvant Therapies for Cancer Treatment)
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16 pages, 17787 KiB  
Article
Development, Stability, and In Vitro/In Vivo Studies of Volatile Oil Pickering Emulsion Stabilized by Modified Amber
by Maomao Zhu, Zhonghuan Qu, Yanjun Yang, Ruyu Shi, Bing Yang, Yajun Shi, Junbo Zou and Xiaobin Jia
Pharmaceuticals 2024, 17(9), 1117; https://doi.org/10.3390/ph17091117 - 24 Aug 2024
Viewed by 310
Abstract
Volatile oil stabilization strategies based on encapsulation with a large number of excipients limit further applications. The primary objective of this study is to improve the stability of volatile oils using Pickering emulsion (PE) stabilized by Chinese medicinal powder based on the principle [...] Read more.
Volatile oil stabilization strategies based on encapsulation with a large number of excipients limit further applications. The primary objective of this study is to improve the stability of volatile oils using Pickering emulsion (PE) stabilized by Chinese medicinal powder based on the principle of “integrating drug and excipient”. Modified amber was acquired through surface modification, and a stable oil-in-water PE loaded with Acorus tatarinowii volatile oil (ATVO) was constructed from modified amber. The stability, including the peroxide value (PV), malondialdehyde (MDA) content, and the content and composition of volatile components in modified amber-PE (MAPE) under intense light exposure, was analyzed deeply. In addition, the in vitro release and pharmacokinetics of MAPE and ATVO were investigated. The results demonstrate that the PV and MDA content in MAPE were significantly lower than in free ATVO, and the content and composition of volatile components in MAPE were closer to those in untreated ATVO. The release kinetics of β-asarone and α-asarone in MAPE demonstrated rapid and higher release, and pharmacokinetic studies show that MAPE has better bioavailability. This research provides a distinctive Chinese medicine solution to address the vaporization of volatile oil in solid formulations. Full article
(This article belongs to the Section Pharmaceutical Technology)
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15 pages, 1800 KiB  
Article
Characterization of Antineoplastic Agents Inducing Taste and Smell Disorders Using the FAERS Database
by Risa Hamazaki and Yoshihiro Uesawa
Pharmaceuticals 2024, 17(9), 1116; https://doi.org/10.3390/ph17091116 - 23 Aug 2024
Viewed by 295
Abstract
Taste and smell disorders can worsen the nutritional status of patients receiving chemotherapy and potentially affect drug treatment. However, there is limited knowledge on antineoplastic agents that induce taste and smell disorders. Therefore, we used the U.S. Food and Drug Administration Adverse Event [...] Read more.
Taste and smell disorders can worsen the nutritional status of patients receiving chemotherapy and potentially affect drug treatment. However, there is limited knowledge on antineoplastic agents that induce taste and smell disorders. Therefore, we used the U.S. Food and Drug Administration Adverse Event Reporting System database to analyze the characteristics of patients and antineoplastic agents in relation to taste and smell disorders. No gender differences related to the onset of taste and smell disorders were found, whereas older age was identified as a possible risk factor. Among the antineoplastic agent classes, protein kinase inhibitors appeared to be particularly likely to induce taste and smell disorders. According to the cluster and principal component analyses, antineoplastic agents were deemed to induce taste or smell disorders. In addition, antineoplastic agents that decreased or changed these sensations could be classified. These findings might be useful in selecting drugs for patients experiencing similar side effects. Full article
(This article belongs to the Special Issue Therapeutic Drug Monitoring and Adverse Drug Reactions)
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11 pages, 260 KiB  
Article
The Impact of Chemotherapy on Arterial Stiffness and Ventricular–Arterial Coupling in Women with Breast Cancer
by Nikolaos P. E. Kadoglou, Alexandriani Dimopoulou, Irene Tsappa, Pampina Pilavaki and Anastasia Constantinidou
Pharmaceuticals 2024, 17(9), 1115; https://doi.org/10.3390/ph17091115 - 23 Aug 2024
Viewed by 300
Abstract
Background: The cardiac toxicity of chemotherapy for breast cancer is not uncommon and has been associated with elevated morbidity and mortality. In the present study, we assessed the impact of chemotherapy on cardiovascular function by assessing the cardio–ankle vascular index (CAVI), global longitudinal [...] Read more.
Background: The cardiac toxicity of chemotherapy for breast cancer is not uncommon and has been associated with elevated morbidity and mortality. In the present study, we assessed the impact of chemotherapy on cardiovascular function by assessing the cardio–ankle vascular index (CAVI), global longitudinal strain (GLS) and ventricular–arterial coupling (VAC: CAVI/GLS ratio) in chemotherapy-treated women. Methods: This prospective study enrolled 78 women with breast cancer who were receiving anthracycline-based chemotherapy +/− anti-HER2 therapy (trastuzumab +/− pertuzumab). Forty-one age-matched healthy women served as controls. We comparatively evaluated left ventricular ejection fraction (LVEF), CAVI, GLS and VAC, between the chemotherapy and control groups. We also assessed their changes over time (baseline, 3-month and 6-month time point) and their independent association with the incidence of cancer therapy-related cardiovascular dysfunction (CTRCD) in the chemotherapy group. Results: In comparison to healthy controls, women receiving chemotherapy presented with significantly higher GLS (from −21.02 ± 2.09% to −19.01 ± 2.81%, p < 0.001) and VAC (−0.36 ± 0.06 to −0.41 ± 0.11, p < 0.001). The presence of CTRCD was associated with a further increase in GLS and CAVI and a significant decline in LVEF and VAC compared to CTRCD-free women (p < 0.001). Baseline, CAVI, GLS and VAC were independently associated with CTRCD development during follow-up. Conclusion: Women with breast cancer undergoing chemotherapy displayed abnormal levels of CAVI, VAC and GLS, compared to healthy individuals. Those effects on VAC and CAVI were more exaggerated among women with CTRCD, implicating their potential use to refine screening and therapeutic strategies for this specific population. Full article
(This article belongs to the Section Pharmacology)
17 pages, 5261 KiB  
Article
Physicochemical Characterization of the Oral Biotherapeutic Drug IMUNOR®
by Jitka Mucksová, Gabriela Borošová, Miloš Blazsek, Jiří Kalina, Lucie Minaříková and Zdeňka Svobodová
Pharmaceuticals 2024, 17(9), 1114; https://doi.org/10.3390/ph17091114 - 23 Aug 2024
Viewed by 325
Abstract
IMUNOR is an oral biotherapeutic drug that had been developed, registered, and approved in 1997 in the Czech Republic and Slovakia. IMUNOR is a dialyzable leukocyte extract (DLE) prepared from swine leukocytes. It is characterized as a mixture of small peptides with molecular [...] Read more.
IMUNOR is an oral biotherapeutic drug that had been developed, registered, and approved in 1997 in the Czech Republic and Slovakia. IMUNOR is a dialyzable leukocyte extract (DLE) prepared from swine leukocytes. It is characterized as a mixture of small peptides with molecular weights smaller than 12 kDa and a specific portion of nucleotides. The medical uses of IMUNOR include therapeutic applications within its registered range of indications, primarily for the treatment of immunodeficiencies, allergies, and certain acute or relapsing bacterial infections in adults and children. Despite the long-term clinical application of DLE, with strong evidence of positive therapeutic effects and no serious side effects, a detailed physicochemical specification of this mixture was lacking. We developed several methods for more in-depth physicochemical characterization of IMUNOR, including a spectrophotometric method for quantification of the total protein concentration and total DNA concentration in a mixture, several chromatographic methods for identification of individual components present in significant concentrations in IMUNOR, such as HPLC methods and the Sodium Dodecyl Sulphate Polyacrylamide Gel Electrophoresis method, and characterization of amino acid composition of this mixture. For the investigation of the variability among different batches of IMUNOR, five to nine representative batches from a standard manufacturing process on an industrial scale were utilized. Using the analytical methods, we verified and confirmed the batch-to-batch reproducibility of the biological product IMUNOR. Full article
(This article belongs to the Section Pharmacology)
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28 pages, 2819 KiB  
Review
Botany, Traditional Use, Phytochemistry, Pharmacology and Quality Control of Taraxaci herba: Comprehensive Review
by Jianhao Wu, Jialin Sun, Meiqi Liu, Xiaozhuang Zhang, Lingyang Kong, Lengleng Ma, Shan Jiang, Xiubo Liu and Wei Ma
Pharmaceuticals 2024, 17(9), 1113; https://doi.org/10.3390/ph17091113 - 23 Aug 2024
Viewed by 275
Abstract
Taraxaci herba, as a traditional Chinese medicine, is the name of the Taraxacum genus in the Asteraceae family. Documented in the Tang Herbal Medicine (Tang Dynasty, AD 657–659), its medicinal properties cover a wide range of applications such as acute mastitis, lung [...] Read more.
Taraxaci herba, as a traditional Chinese medicine, is the name of the Taraxacum genus in the Asteraceae family. Documented in the Tang Herbal Medicine (Tang Dynasty, AD 657–659), its medicinal properties cover a wide range of applications such as acute mastitis, lung abscess, conjunctival congestion, sore throat, damp-heat jaundice, and vision improvement. In the Chinese Pharmacopoeia (Edition 2020), more than 40 kinds of China-patented drugs containing Taraxaci herba were recorded. This review explores the evolving scientific understanding of Taraxaci herba, covering facets of ethnopharmacology, botany, phytochemistry, pharmacology, artificial cultivation, and quality control. In particular, the chemical constituents and pharmacological research are reviewed. Taraxaci herba has been certified as a traditional medicine plant, and its flavonoids, phenolic acids, and terpenoids have been identified and separated, which include Chicoric acid, taraxasterol, Taraxasteryl acetate, Chlorogenic acid, isorhamnetin, and luteolin; they are responsible for anti-inflammatory, antioxidant, antibacterial, anti-tumor, and anti-cancer activities. These findings validate the traditional uses of Taraxaci herba and lay the groundwork for further scientific exploration. The sources used in this study include Web of Science, Pubmed, the CNKI site, classic monographs, the Chinese Pharmacopoeia, the Chinese Medicine Dictionary, and doctoral and master’s theses. Full article
(This article belongs to the Section Natural Products)
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16 pages, 2819 KiB  
Article
Hair Growth Promoting Effects of Solubilized Sturgeon Oil and Its Correlation with the Gut Microbiome
by Jihee Kim, Jinho An, Yong-kwang Lee, Gwangsu Ha, Hamin Ban, Hyunseok Kong, Heetae Lee, Youngcheon Song, Chong-kil Lee, Sang Bum Kim and Kyungjae Kim
Pharmaceuticals 2024, 17(9), 1112; https://doi.org/10.3390/ph17091112 - 23 Aug 2024
Viewed by 311
Abstract
Androgenetic alopecia is a common disease that occurs in both men and women. Several approved medications have been used to treat this condition, but they are associated with certain side effects. Therefore, use of extracts derived from natural products, such as Siberian sturgeon [...] Read more.
Androgenetic alopecia is a common disease that occurs in both men and women. Several approved medications have been used to treat this condition, but they are associated with certain side effects. Therefore, use of extracts derived from natural products, such as Siberian sturgeon (Acipenser baerii), and the regulation of the gut microbiota have become important topics of research. Sturgeon is known for its high nutritional value and anti-inflammatory properties; however, its effects on androgenetic alopecia and gut microbiota remain uncharacterized. Here, we aimed to investigate whether solubilized sturgeon oil (SSO) promotes hair growth and regulates the gut microbiome. C57BL/6 mice were divided into four groups. Three groups received topical applications of distilled water, SSO, or minoxidil, and one group was orally administered SSO. Each treatment was administered over 4 weeks. Histopathological analysis revealed a significant increase in follicle number (p < 0.001) and follicle diameter (p < 0.05). Immunohistochemical analysis revealed upregulation of β-catenin and ERK-1, markers involved in hair growth-promoting pathways. Furthermore, microbiome analysis revealed that the reduced gut microbiota was negatively correlated with these markers. Our findings indicate that oral administration of SSO promotes hair growth and regulates the abundance of hair growth-promoting gut microbiota. Full article
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19 pages, 3162 KiB  
Case Report
Harnessing the Interactions of Wound Exudate Cells with Dressings Biomaterials for the Control and Prognosis of Healing Pathways
by Shirin Saberianpour, Gianluca Melotto, Lucy Redhead, Nadia Terrazzini, Jaqueline Rachel Forss and Matteo Santin
Pharmaceuticals 2024, 17(9), 1111; https://doi.org/10.3390/ph17091111 - 23 Aug 2024
Viewed by 277
Abstract
The global socioeconomic challenge generated by wounds requires an understanding of healing and non-healing pathways in patients. Also, the interactions occurring between the wound dressing biomaterials with cells relevant to the healing process have not been sufficiently investigated, thus neglecting the role that [...] Read more.
The global socioeconomic challenge generated by wounds requires an understanding of healing and non-healing pathways in patients. Also, the interactions occurring between the wound dressing biomaterials with cells relevant to the healing process have not been sufficiently investigated, thus neglecting the role that wound dressing composition can play in healing. Through the study of six cases of acute surgical wounds, the present work analyses the early (24 h post-surgery) interactions of biochemical and cellular components with (i) Atrauman, a device made of knitted woven synthetic polymeric fibre when used as a primary dressing, and (ii) Melolin, a hydrocolloid engineered as two layers of synthetic and cellulose non-woven fibres when used as a secondary dressing. A pathway towards healing could be observed in those cases where endoglin-expressing cells and M2 macrophages were retained by Atrauman fibres at the interface with the wound bed. On the contrary, cases where the secondary dressing Melolin absorbed these cell phenotypes in its mesh resulted in a slower or deteriorating healing process. The data obtained indicate that a subtraction of progenitor cells by Melolin may impair the healing process and that the analysis of the retrieved wound dressings for biomarkers expressed by cells relevant to wound healing may become an additional tool to determine the patient’s prognosis. Full article
(This article belongs to the Special Issue Development of Specific Dosage Form: Wound Dressing)
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18 pages, 1783 KiB  
Review
An Overview of Wound Dressing Materials
by Tânia Lagoa, Maria Cristina Queiroga and Luís Martins
Pharmaceuticals 2024, 17(9), 1110; https://doi.org/10.3390/ph17091110 - 23 Aug 2024
Viewed by 680
Abstract
Wounds are an increasing global concern, mainly due to a sedentary lifestyle, frequently associated with the occidental way of life. The current prevalence of obesity in Western societies, leading to an increase in type II diabetes, and an elderly population, is also a [...] Read more.
Wounds are an increasing global concern, mainly due to a sedentary lifestyle, frequently associated with the occidental way of life. The current prevalence of obesity in Western societies, leading to an increase in type II diabetes, and an elderly population, is also a key factor associated with the problem of wound healing. Therefore, it stands essential to find wound dressing systems that allow for reestablishing the skin integrity in the shortest possible time and with the lowest cost, avoiding further damage and promoting patients’ well-being. Wounds can be classified into acute or chronic, depending essentially on the duration of the healing process, which is associated withextent and depth of the wound, localization, the level of infection, and the patient’s health status. For each kind of wound and respective healing stage, there is a more suitable dressing. The aim of this review was to focus on the possible wound dressing management, aiming for a more adequate healing approach for each kind of wound. Full article
(This article belongs to the Section Pharmaceutical Technology)
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15 pages, 728 KiB  
Article
Exploring the Antibiofilm Effect of Sertraline in Synergy with Cinnamomum verum Essential Oil to Counteract Candida Species
by Alexia Barbarossa, Antonio Rosato, Antonio Carrieri, Luciana Fumarola, Roberta Tardugno, Filomena Corbo, Giuseppe Fracchiolla and Alessia Carocci
Pharmaceuticals 2024, 17(9), 1109; https://doi.org/10.3390/ph17091109 - 23 Aug 2024
Viewed by 341
Abstract
The emergence and spread of drug-resistant pathogens, resulting in antimicrobial resistance, continue to compromise our capability to handle commonly occurring infectious diseases. The rapid global spread of multi-drug-resistant pathogens, particularly systemic fungal infections, presents a significant concern, as existing antimicrobial drugs are becoming [...] Read more.
The emergence and spread of drug-resistant pathogens, resulting in antimicrobial resistance, continue to compromise our capability to handle commonly occurring infectious diseases. The rapid global spread of multi-drug-resistant pathogens, particularly systemic fungal infections, presents a significant concern, as existing antimicrobial drugs are becoming ineffective against them. In recent decades, there has been a notable increase in systemic fungal infections, primarily caused by Candida species, which are progressively developing resistance to azoles. Moreover, Candida species biofilms are among the most common in clinical settings. In particular, they adhere to biomedical devices, growing as a resilient biofilm capable of withstanding extraordinarily high antifungal concentrations. In recent years, many research programs have concentrated on the development of novel compounds with possible antimicrobial effects to address this issue, and new sources, such as plant-derived antimicrobial compounds, have been thoroughly investigated. Essential oils (EOs), among their numerous pharmacological properties, exhibit antifungal, antibacterial, and antiviral activities and have been examined at a global scale as the possible origin of novel antimicrobial compounds. A recent work carried out by our research group concerned the synergistic antibacterial activities of commercially available and chemically characterized Cinnamomum verum L. essential oil (C. verum EO) in association with sertraline, a selective serotonin reuptake inhibitor whose repositioning as a non-antibiotic drug has been explored over the years with encouraging results. The aim of this work was to explore the synergistic effects of C. verum EO with sertraline on both planktonic and sessile Candida species cells. Susceptibility testing and testing of the synergism of sertraline and C. verum EO against planktonic and sessile cells were performed using a broth microdilution assay and checkerboard methods. A synergistic effect was evident in both the planktonic cells and mature biofilms, with significant reductions in fungal viability. Indeed, the fractional inhibitory concentration index (FICI) was lower than 0.5 for all the associations, thus indicating significant synergism of the associations with the Candida strains examined. Moreover, the concentrations of sertraline able to inhibit Candida spp. strain growth and biofilm formation significantly decreased when it was used in combination with C. verum EO for all the strains considered, with a reduction percentage in the amount of each associated component ranging from 87.5% to 97%. Full article
(This article belongs to the Special Issue Natural Anti-Biofilm Agents)
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62 pages, 15058 KiB  
Review
Approachable Synthetic Methodologies for Second-Generation β-Lactamase Inhibitors: A Review
by Noor Fatima, Shehla Khalid, Nasir Rasool, Muhammad Imran, Bushra Parveen, Aqsa Kanwal, Marius Irimie and Codrut Ioan Ciurea
Pharmaceuticals 2024, 17(9), 1108; https://doi.org/10.3390/ph17091108 - 23 Aug 2024
Viewed by 369
Abstract
Some antibiotics that are frequently employed are β-lactams. In light of the hydrolytic process of β-lactamase, found in Gram-negative bacteria, inhibitors of β-lactamase (BLIs) have been produced. Examples of first-generation β-lactamase inhibitors include sulbactam, clavulanic acid, and tazobactam. Many [...] Read more.
Some antibiotics that are frequently employed are β-lactams. In light of the hydrolytic process of β-lactamase, found in Gram-negative bacteria, inhibitors of β-lactamase (BLIs) have been produced. Examples of first-generation β-lactamase inhibitors include sulbactam, clavulanic acid, and tazobactam. Many kinds of bacteria immune to inhibitors have appeared, and none cover all the β-lactamase classes. Various methods have been utilized to develop second-generation β-lactamase inhibitors possessing new structures and facilitate the formation of diazabicyclooctane (DBO), cyclic boronate, metallo-, and dual-nature β-lactamase inhibitors. This review describes numerous promising second-generation β-lactamase inhibitors, including vaborbactam, avibactam, and cyclic boronate serine-β-lactamase inhibitors. Furthermore, it covers developments and methods for synthesizing MβL (metallo-β-lactamase inhibitors), which are clinically effective, as well as the various dual-nature-based inhibitors of β-lactamases that have been developed. Several combinations are still only used in preclinical or clinical research, although only a few are currently used in clinics. This review comprises materials on the research progress of BLIs over the last five years. It highlights the ongoing need to produce new and unique BLIs to counter the appearance of multidrug-resistant bacteria. At present, second-generation BLIs represent an efficient and successful strategy. Full article
(This article belongs to the Section Medicinal Chemistry)
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20 pages, 4294 KiB  
Article
In Silico Exploration of Novel EGFR Kinase Mutant-Selective Inhibitors Using a Hybrid Computational Approach
by Md Ali Asif Noor, Md Mazedul Haq, Md Arifur Rahman Chowdhury, Hilal Tayara, HyunJoo Shim and Kil To Chong
Pharmaceuticals 2024, 17(9), 1107; https://doi.org/10.3390/ph17091107 - 23 Aug 2024
Viewed by 527
Abstract
Targeting epidermal growth factor receptor (EGFR) mutants is a promising strategy for treating non-small cell lung cancer (NSCLC). This study focused on the computational identification and characterization of potential EGFR mutant-selective inhibitors using pharmacophore design and validation by deep learning, virtual screening, ADMET [...] Read more.
Targeting epidermal growth factor receptor (EGFR) mutants is a promising strategy for treating non-small cell lung cancer (NSCLC). This study focused on the computational identification and characterization of potential EGFR mutant-selective inhibitors using pharmacophore design and validation by deep learning, virtual screening, ADMET (Absorption, distribution, metabolism, excretion and toxicity), and molecular docking-dynamics simulations. A pharmacophore model was generated using Pharmit based on the potent inhibitor JBJ-125, which targets the mutant EGFR (PDB 5D41) and is used for the virtual screening of the Zinc database. In total, 16 hits were retrieved from 13,127,550 molecules and 122,276,899 conformers. The pharmacophore model was validated via DeepCoy, generating 100 inactive decoy structures for each active molecule and ADMET tests were conducted using SWISS ADME and PROTOX 3.0. Filtered compounds underwent molecular docking studies using Glide, revealing promising interactions with the EGFR allosteric site along with better docking scores. Molecular dynamics (MD) simulations confirmed the stability of the docked conformations. These results bring out five novel compounds that can be evaluated as single agents or in combination with existing therapies, holding promise for treating the EGFR-mutant NSCLC. Full article
(This article belongs to the Special Issue Heterocyclic Compounds in Medicinal Chemistry)
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16 pages, 586 KiB  
Review
Gastrointestinal Manifestations of Sarcoidosis: A State-of-the-Art, Comprehensive Review of the Literature—Practical Clinical Insights and Many Unmet Needs on Diagnosis and Treatment
by Salvatore Nicolosi, Maria Chernovsky, Darina Angoni, Michael Hughes, Giulia Bandini, Zsuzsanna McMahan, Marta Maggisano, Francesco Salton, Lucrezia Mondini, Mariangela Barbieri, Gianluca Screm, Marco Confalonieri, Elisa Baratella, Paola Confalonieri and Barbara Ruaro
Pharmaceuticals 2024, 17(9), 1106; https://doi.org/10.3390/ph17091106 - 23 Aug 2024
Viewed by 359
Abstract
This comprehensive literature review explores the involvement of the gastrointestinal (GI) tract in sarcoidosis, a multisystem granulomatous disorder of unknown etiology. GI sarcoidosis presents a diagnostic and therapeutic challenge due to its rarity and nonspecific clinical manifestations, including overlap with other gastrointestinal diseases. [...] Read more.
This comprehensive literature review explores the involvement of the gastrointestinal (GI) tract in sarcoidosis, a multisystem granulomatous disorder of unknown etiology. GI sarcoidosis presents a diagnostic and therapeutic challenge due to its rarity and nonspecific clinical manifestations, including overlap with other gastrointestinal diseases. We conducted a comprehensive screening of articles addressing the clinical features, diagnostic approaches, and treatment strategies for GI sarcoidosis. Our findings reveal that GI sarcoidosis can affect any part of the gastrointestinal tract, with the stomach and small intestine being the most involved. Clinical presentations range from asymptomatic cases to severe complications such as obstruction and perforation, with reflux being a common symptom. Diagnosis is often delayed due to the nonspecific nature of symptoms and the need for histopathological confirmation. Therapeutic approaches are poorly defined, typically involving corticosteroids as the mainstay of treatment. However, the long-term efficacy and safety of these treatments remain uncertain in this patient group, given the significant risks and complications associated with prolonged glucocorticoid therapy. There is a clear need to develop accurate diagnostic protocols to distinguish GI sarcoidosis from other conditions and to establish standardized therapeutic guidelines to optimize patient outcomes. Further research is essential to enhance our understanding and management of this complex condition. Full article
(This article belongs to the Special Issue New and Emerging Treatment Strategies for Gastrointestinal Diseases)
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