Current Issues in Molecular Biology

10 pages, 1722 KiB

Open AccessArticle

Evaluation of the Influence of Varied Juncao Grass Substrates on Physiological and Enzymatic Reactions of Pleurotus ostreatus

by Irambona Claude, Nsanzinshuti Aimable, Hatungimana Mediatrice, Hengyu Zhou, Dongmei Lin, Penghu Liu and Zhanxi Lin

Curr. Issues Mol. Biol. 2024, 46(9), 9493-9502; https://doi.org/10.3390/cimb46090563 (registering DOI) - 28 Aug 2024

Abstract

Pleurotus ostreutus is one of the world’s most commonly consumed mushrooms. The cultivation of mushrooms using wood resources usually results in environmental issues such as deforestation. Juncao grasses, namely (JJ) Cenchrus fungigraminus, (AR) Saccharum arundinaceum, and (MS) Miscanthus floridulus, supplemented [...] Read more.

Pleurotus ostreutus is one of the world’s most commonly consumed mushrooms. The cultivation of mushrooms using wood resources usually results in environmental issues such as deforestation. Juncao grasses, namely (JJ) Cenchrus fungigraminus, (AR) Saccharum arundinaceum, and (MS) Miscanthus floridulus, supplemented with 20% wheat brain, 1% ground coffee, 1% gysum, and 1% lime, were used as the culture mediums in this research, which offers a composting system with a simple formulation that is cheap and feasible for small farms to use in cultivating oyster mushrooms. The present study assessed the different juncao grasses as substrates for growing Pleurotus ostreatus given their enzyme activities, growth, and yields. The results demonstrated that the yields of pleurotus ostreatus grown on JJ, AR, and MS substrates were significantly different at the level of 0.05 and were recorded as follows: 159.2 g/bag, 132 g/bag, and 65.1 g/bag on average, respectively. The biological efficiency of Pleurotus ostreatus cultivated in three different substrates was 75.2%, 63.4%, and 28.7%, respectively. Lignin peroxidase (LiP) was the most active enzyme in each culture material among the other enzyme activities expressed differently between the substrate and growing stages. At the same time, other enzyme activities were differently expressed between the substrate and different developmental stages. Nutrient analysis revealed significant variations, with differences in polysaccharides, proteins, and amino acids among substrates, as well as the presence of heavy metals such as arsenic, lead, mercury, and cadmium in all samples within safe limits. The obtained results indicated that Saccharum arundinaceum is a good substrate in place of Cenchrus fungigraminus, and that using Miscanthus floridulus is not productive. Moreover, the juncao grasses offer a sustainable approach that reduces reliance on wood-based substrates and enhances environmental sustainability. Full article

(This article belongs to the Section Molecular Microbiology)

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13 pages, 3443 KiB

Open AccessReview

The Role of Caspases in Melanoma Pathogenesis

by Agnieszka Szmurło, Klaudia Dopytalska, Michał Szczerba, Elżbieta Szymańska, Alicja Petniak, Marcin Kocki, Janusz Kocki and Irena Walecka

Curr. Issues Mol. Biol. 2024, 46(9), 9480-9492; https://doi.org/10.3390/cimb46090562 - 28 Aug 2024

Abstract

Melanoma (malignant melanoma, MM) is an aggressive malignant skin cancer with an increasing incidence rate. The complete pathogenesis of MM in not clear. Due to DNA damage, mutations, dysregulation of growth factors, inactivation of tumor suppressor genes, and activation of oncogenes, excessive uncontrolled [...] Read more.

Melanoma (malignant melanoma, MM) is an aggressive malignant skin cancer with an increasing incidence rate. The complete pathogenesis of MM in not clear. Due to DNA damage, mutations, dysregulation of growth factors, inactivation of tumor suppressor genes, and activation of oncogenes, excessive uncontrolled growth of abnormal melanocytes occurs in melanomas. Caspases are a group of proteolytic enzymes that participate in several processes important in regulating mechanisms at the cellular level. They play a role in cell homeostasis and programmed cell death (apoptosis) and in the regulation of non-apoptotic cell death processes. Dysregulation of caspase activation plays a role in the etiology of cancers, including melanoma. Caspases can initiate and execute apoptosis and are involved in regulating cell death and controlling tumor growth. These enzymes also inhibit tumor growth by cleaving and inactivating proteins that are involved in cell proliferation and angiogenesis. Moreover, caspases are involved in the activation of immune processes through the processing and presentation of tumor antigens, which facilitates recognition of the tumor by the immune system. The role of caspases in melanoma is complex, and they may inhibit melanoma growth and progression. This work aims to review the current knowledge of the role of individual caspases in melanoma pathogenesis. Full article

(This article belongs to the Special Issue Advances in Pharmacotherapeutic Strategies to Prevent Tumor Development, Progression and Treatment Resistance)

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17 pages, 5985 KiB

Open AccessReview

NOD1 and NOD2: Essential Monitoring Partners in the Innate Immune System

by Zhenjia Li and Dejing Shang

Curr. Issues Mol. Biol. 2024, 46(9), 9463-9479; https://doi.org/10.3390/cimb46090561 - 28 Aug 2024

Abstract

Nucleotide-binding oligomerization domain containing 1 (NOD1) and NOD2 are pivotal cytoplasmic pattern-recognition receptors (PRRs) that exhibit remarkable evolutionary conservation. They possess the ability to discern specific peptidoglycan (PGN) motifs, thereby orchestrating innate immunity and contributing significantly to immune homeostasis maintenance. The comprehensive understanding [...] Read more.

Nucleotide-binding oligomerization domain containing 1 (NOD1) and NOD2 are pivotal cytoplasmic pattern-recognition receptors (PRRs) that exhibit remarkable evolutionary conservation. They possess the ability to discern specific peptidoglycan (PGN) motifs, thereby orchestrating innate immunity and contributing significantly to immune homeostasis maintenance. The comprehensive understanding of both the structure and function of NOD1 and NOD2 has been extensively elucidated. These receptors proficiently recognize an array of damage-associated molecular patterns (DAMPs) as well as pathogen-associated molecular patterns (PAMPs), subsequently mediating inflammatory responses and autophagy. In recent years, emerging evidence has highlighted the crucial roles played by NOD1 and NOD2 in regulating infectious diseases, metabolic disorders, cancer, and autoimmune conditions, among others. Perturbation in either their loss or excessive activation can detrimentally impact immune homeostasis. This review offers a comprehensive overview of the structural characteristics, subcellular localization, activation mechanisms, and significant roles of NOD1 and NOD2 in innate immunity and related disease. Full article

(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)

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15 pages, 2170 KiB

Open AccessArticle

Selection and Validation of Reliable Reference Genes for Liquidambar formosana Leaves with Different Leaf Colors

by Fangwei Zhou, Liang Xu, Congguang Shi, Shaozong Yang and Yahui Chen

Curr. Issues Mol. Biol. 2024, 46(9), 9449-9462; https://doi.org/10.3390/cimb46090560 - 27 Aug 2024

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Abstract

Liquidambar formosana Hance is renowned for its rich leaf color and possesses notable advantages, such as robust adaptability, strong resistance to diseases and pests, and rapid growth, making it a preferred choice for urban greening and carbon sequestration forest initiatives. The completion of [...] Read more.

Liquidambar formosana Hance is renowned for its rich leaf color and possesses notable advantages, such as robust adaptability, strong resistance to diseases and pests, and rapid growth, making it a preferred choice for urban greening and carbon sequestration forest initiatives. The completion of whole-genome sequencing of L. formosana has spurred an increased interest in exploring the molecular mechanisms underlying seasonal changes in leaf color, marking a significant focus in L. formosana breeding research. However, there is currently a lack of stable reference genes suitable for analyzing the expression patterns of functional genes in L. formosana exhibiting varying leaf colors. This study selected five L. formosana varieties with significant differences in leaf colors. Through the RT-qPCR analysis, and evaluation using BestKeeper, geNorm, NormFinder, Delta Ct, and RefFinder, the expression stability of 14 candidate reference genes was examined. Consequently, two reference genes (LifEF1-α and LifACT) with stable expression, suitable for RT-qPCR of L. formosana with diverse leaf colors, were identified. The stability of these selected reference genes was further validated by examining the LifbHLH137 gene, which promoted the biosynthesis of anthocyanins. This advancement facilitated molecular biology and genetic breeding investigations of L. formosana, providing essential data for the precise quantification of functional genes associated with leaf color variation. Full article

(This article belongs to the Section Molecular Plant Sciences)

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19 pages, 1855 KiB

Open AccessReview

Extracellular Vesicle-Derived Non-Coding RNAs: Key Mediators in Remodelling Heart Failure

by Jiayi Zhao and Huang Huang

Curr. Issues Mol. Biol. 2024, 46(9), 9430-9448; https://doi.org/10.3390/cimb46090559 - 27 Aug 2024

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Abstract

Heart failure (HF), a syndrome of persistent development of cardiac insufficiency due to various heart diseases, is a serious and lethal disease for which specific curative therapies are lacking and poses a severe burden on all aspects of global public health. Extracellular vesicles [...] Read more.

Heart failure (HF), a syndrome of persistent development of cardiac insufficiency due to various heart diseases, is a serious and lethal disease for which specific curative therapies are lacking and poses a severe burden on all aspects of global public health. Extracellular vesicles (EVs) are essential mediators of intercellular and interorgan communication, and are enclosed nanoscale vesicles carrying biomolecules such as RNA, DNA, and proteins. Recent studies have showed, among other things, that non-coding RNAs (ncRNAs), especially microRNAs (miRNAs), long ncRNAs (lncRNA), and circular RNAs (circRNAs) can be selectively sorted into EVs and modulate the pathophysiological processes of HF in recipient cells, acting on both healthy and diseased hearts, which makes them promising targets for the diagnosis and therapy of HF. This review aims to explore the mechanism of action of EV-ncRNAs in heart failure, with emphasis on the potential use of differentially expressed miRNAs and circRNAs as biomarkers of cardiovascular disease, and recent research advances in the diagnosis and treatment of heart failure. Finally, we focus on summarising the latest advances and challenges in engineering EVs for HF, providing novel concepts for the diagnosis and treatment of heart failure. Full article

(This article belongs to the Special Issue Exosomes in Tissue Regeneration and Disease Therapy)

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15 pages, 41414 KiB

Open AccessArticle

A Theoretical Study of the Interaction of PARP-1 with Natural and Synthetic Inhibitors: Advances in the Therapy of Triple-Negative Breast Cancer

by Albert Gabriel Turpo-Peqqueña, Emily Katherine Leiva-Flores, Sebastián Luna-Prado and Badhin Gómez

Curr. Issues Mol. Biol. 2024, 46(9), 9415-9429; https://doi.org/10.3390/cimb46090558 - 27 Aug 2024

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Abstract

In the current study, we have investigated the secondary metabolites present in ethnomedical plants used for medicinal purposes—Astilbe chinensis (EK1), Scutellaria barbata D. Don (EK2), Uncaria rhynchophylla (EK3), Fallugia paradoxa (EK4), and Curcuma zedoaria (Christm.) Thread (EK5)—and we have compared them with five [...] Read more.

In the current study, we have investigated the secondary metabolites present in ethnomedical plants used for medicinal purposes—Astilbe chinensis (EK1), Scutellaria barbata D. Don (EK2), Uncaria rhynchophylla (EK3), Fallugia paradoxa (EK4), and Curcuma zedoaria (Christm.) Thread (EK5)—and we have compared them with five compounds of synthetic origin for the inhibition of PARP-1, which is linked to abnormal DNA replication, generating carcinogenic cells. We have studied these interactions through molecular dynamics simulations of each interacting system under physiological conditions (pH, temperature, and pressure) and determined that the compounds of natural origin have a capacity to inhibit PARP-1 (Poly(ADP-ribose) Polymerase 1) in all the cases inspected in this investigation. However, it is essential to mention that their interaction energy is relatively lower compared to that of compounds of synthetic origin. Given that binding energy is mandatory for the generation of a scale or classification of which is the best interacting agent, we can say that we assume that compounds of natural origin, having a complexation affinity with PARP-1, induce cell apoptosis, a potential route for the prevention of the proliferation of carcinogenic cells. Full article

(This article belongs to the Collection Bioinformatics Approaches to Biomedicine)

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14 pages, 1893 KiB

Open AccessArticle

Possible Role of NRF2 in Cell Response to OZOILE (Stable Ozonides) in Children Affected by Lichen Sclerosus of Foreskin

by Caterina Saija, Monica Currò, Salvatore Arena, Maria Paola Bertuccio, Fabiola Cassaro, Angela Simona Montalto, Michele Rosario Colonna, Daniela Caccamo, Carmelo Romeo and Pietro Impellizzeri

Curr. Issues Mol. Biol. 2024, 46(9), 9401-9414; https://doi.org/10.3390/cimb46090557 - 26 Aug 2024

Viewed by 181

Abstract

Lichen sclerosus (LS) is a chronic inflammatory disease of the skin, and the gold standard for treatment is the use of the very potent topical steroids, but they can have side effects. Previously, we demonstrated that OZOILE (stable ozonides) were effective in children [...] Read more.

Lichen sclerosus (LS) is a chronic inflammatory disease of the skin, and the gold standard for treatment is the use of the very potent topical steroids, but they can have side effects. Previously, we demonstrated that OZOILE (stable ozonides) were effective in children affected by LS, reducing the inflammatory process and stimulating tissue regeneration of the foreskin, showing a similar efficacy to steroid treatment. In this study, the modulation of inflammatory and oxidative stress pathways was evaluated by qRT-PCR and Western blotting in foreskins affected by LS removed from patients untreated or treated with OZOILE or corticosteroid cream formulations for 7 days before circumcision. OZOILE induced a significant increase in NRF2 and SOD2 levels, while it did not produce change in MIF, NF-kB subunits, and MMPs in comparison to untreated foreskins. Conversely, steroid topical treatment produced a significant reduction in the expression of p65, MIF, and MMP9, but it did not cause variation in NRF2 and SOD2 levels. These results demonstrate that the use of OZOILE as cream formulation exhibits effects on NRF2 signaling, and it does not induce NF-κB activation, unlike corticosteroids. On the basis of our biochemical data, further studies evaluating the role of NRF2 signaling cascade are necessary. Full article

(This article belongs to the Special Issue The Role of Bioactives in Inflammation)

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15 pages, 2856 KiB

Open AccessArticle

Promising Support Coming from Nature: Antioxidant and Anti-Inflammatory Potential of Castanea sativa Wood Distillate on Skin Cells

by Arianna Filippelli, Valerio Ciccone, Stefano Loppi and Lucia Morbidelli

Curr. Issues Mol. Biol. 2024, 46(9), 9386-9400; https://doi.org/10.3390/cimb46090556 - 26 Aug 2024

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Abstract

Tissue homeostasis, function recovery, and protection mechanisms are boosted by the balanced and timely control of inflammation and oxidative stress. Nowadays, many natural products and bio-derivates exhibit antioxidant and anti-inflammatory activity, supporting medical care and tissue wellness against inflammation, oxidative stress, and inflammaging. [...] Read more.

Tissue homeostasis, function recovery, and protection mechanisms are boosted by the balanced and timely control of inflammation and oxidative stress. Nowadays, many natural products and bio-derivates exhibit antioxidant and anti-inflammatory activity, supporting medical care and tissue wellness against inflammation, oxidative stress, and inflammaging. Castanea sativa wood distillate (WD) is a bio-derivative used as a corroborant and biofertilizer in agriculture. Based on the safety profile of low concentrations of WD on human cells, the present study aims to assess the anti-inflammatory and antioxidant activity of WD on different cell types in the integumentary system. Human keratinocytes, mucosal epithelium, dermal fibroblasts, and endothelial cells were exposed to WD, and the concentrations devoid of pro-apoptotic potential were profiled. Then, the effect of nontoxic doses of WD revealed an anti-inflammatory effect, observed through the immunodetection of prostanoid cascade markers in experimentally induced inflammation. A reduction in endothelial hyperpermeability was evidenced by the immunofluorescence analysis of cell–cell adhesion proteins, VE-cadherin and ZO-1. In addition, WD buffered the exogenously produced oxidative stress. On the whole, WD showed both anti-inflammatory and antioxidant activities on the various cell types, preserving endothelial barrier integrity. Overall, this study supports the involvement of this bio-derivative in novel exploitable fields, such as therapeutic dermatological applications for human and animal medical care. Full article

(This article belongs to the Section Molecular Pharmacology)

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10 pages, 2447 KiB

Open AccessArticle

Molecular Analysis of High-Grade Serous Ovarian Carcinoma Exhibiting Low-Grade Serous Carcinoma and Serous Borderline Tumor

by Kosuke Kanno, Kentaro Nakayama, Sultana Razia, Sohel Hasibul Islam, Zahan Umme Farzana, Shahataj Begum Sonia, Hiroki Sasamori, Hitomi Yamashita, Tomoka Ishibashi, Masako Ishikawa, Kayo Imamura, Noriyoshi Ishikawa and Satoru Kyo

Curr. Issues Mol. Biol. 2024, 46(9), 9376-9385; https://doi.org/10.3390/cimb46090555 - 25 Aug 2024

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Abstract

Ovarian cancer is classified as type 1 or 2, representing low- and high-grade serous carcinoma (LGSC and HGSC), respectively. LGSC arises from serous borderline tumor (SBT) in a stepwise manner, while HGSC develops from serous tubal intraepithelial carcinoma (STIC). Rarely, HGSC develops from [...] Read more.

Ovarian cancer is classified as type 1 or 2, representing low- and high-grade serous carcinoma (LGSC and HGSC), respectively. LGSC arises from serous borderline tumor (SBT) in a stepwise manner, while HGSC develops from serous tubal intraepithelial carcinoma (STIC). Rarely, HGSC develops from SBT and LGSC. Herein, we describe the case of a patient with HGSC who presented with SBT and LGSC, and in whom we analyzed the molecular mechanisms of carcinogenesis. We performed primary debulking surgery, resulting in a suboptimal simple total hysterectomy and bilateral salpingo-oophorectomy due to strong adhesions. The diagnosis was stage IIIC HGSC, pT3bcN0cM0, but the tumor contained SBT and LGSC lesions. After surgery, TC (Paclitaxel + Carbopratin) + bevacizumab therapy was administered as adjuvant chemotherapy followed by bevacizumab as maintenance therapy. The tumor was chemo-resistant and caused ileus, and bevacizumab therapy was conducted only twice. Next-Generation Sequencing revealed KRAS (p.G12V) and NF2 (p.W184*) mutations in all lesions. Interestingly, the TP53 mutation was not detected in every lesion, and immunohistochemistry showed those lesions with wild-type p53. MDM2 was amplified in the HGSC lesions. DNA methylation analysis did not show differentially methylated regions. This case suggests that SBT and LGSC may transform into HGSC via p53 dysfunction due to MDM2 amplification. Full article

(This article belongs to the Section Molecular Microbiology)

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17 pages, 2500 KiB

Open AccessArticle

Genomic Exploration of a Chitinolytic Streptomyces albogriseolus PMB5 Strain from European mantis (Mantis religiosa)

by Vesselin Baev, Ivan Iliev, Elena Apostolova, Mariyana Gozmanova, Yana Hristova, Yanitsa Ilieva, Galina Yahubyan and Velizar Gochev

Curr. Issues Mol. Biol. 2024, 46(9), 9359-9375; https://doi.org/10.3390/cimb46090554 - 24 Aug 2024

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Abstract

The genus Streptomyces is renowned not only for its natural antibiotic production but also for its abundant chitinolytic enzymes, which break down stubborn chitin into chitooligosaccharides. Despite this, there have been limited studies utilizing whole-genome sequencing to explore the repertoire of chitin degradation [...] Read more.

The genus Streptomyces is renowned not only for its natural antibiotic production but also for its abundant chitinolytic enzymes, which break down stubborn chitin into chitooligosaccharides. Despite this, there have been limited studies utilizing whole-genome sequencing to explore the repertoire of chitin degradation and utilization genes in Streptomyces. A particularly compelling source of novel antimicrobials and enzymes lies in the microbiota of insects, where bacterial symbionts produce antimicrobials to protect against opportunistic pathogens and enzymes to adapt to the environment. In this study, we present the chitinolytic strain Streptomyces albogriseolus PMB5, isolated from the insectivorous Mantis religiosa (European mantis). Whole-genome sequencing revealed that PMB5 harbors a linear chromosome of 7,211,961 bp and a linear plasmid of 327,989 bp. The genome comprises 6683 genes, including 6592 protein-coding sequences and 91 RNA genes. Furthermore, genome analysis revealed 19 biosynthetic gene clusters covering polyketides, terpenes, and RiPPs, with 10 clusters showing significant gene similarity (>80%) to known clusters like antimycin, hopene, and geosmin. In the genome of S. albogriseolus PMB5, we were able to identify several antibiotic resistance genes; these included cml (resistance to phenicol), gimA (resistance to macrolides), parY (resistance to aminocoumarin), oleC/oleD (resistance to macrolides), novA (resistance to aminocoumarin) and bla/blc (resistance to beta-lactams). Additionally, three clusters displayed no similarity to known sequences, suggesting novel bioactive compound discovery potential. Remarkably, strain PMB5 is the first reported S. albogriseolus capable of thriving on a medium utilizing chitin as a carbon source, with over 50 chitin-utilizing genes identified, including five AA10 family LPMOs, five GH18 chitinases, and one GH19 chitinase. This study significantly enhances the genomic understanding of S. albogriseolus, a species previously underrepresented in research, paving the way to further exploration of the biotechnological potential of the species. Full article

(This article belongs to the Section Molecular Microbiology)

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17 pages, 2660 KiB

Open AccessArticle

The ER Stress Induced in Human Neuroblastoma Cells Can Be Reverted by Lumacaftor, a CFTR Corrector

by Michela Pecoraro, Adele Serra, Maria Pascale and Silvia Franceschelli

Curr. Issues Mol. Biol. 2024, 46(9), 9342-9358; https://doi.org/10.3390/cimb46090553 - 24 Aug 2024

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Abstract

Most neurodegenerative diseases share a common etiopathogenesis, the accumulation of protein aggregates. An imbalance in homeostasis brought on by the buildup of misfolded proteins within the endoplasmic reticulum (ER) results in ER stress in the cell. Three distinct proteins found in the ER [...] Read more.

Most neurodegenerative diseases share a common etiopathogenesis, the accumulation of protein aggregates. An imbalance in homeostasis brought on by the buildup of misfolded proteins within the endoplasmic reticulum (ER) results in ER stress in the cell. Three distinct proteins found in the ER membrane—IRE1α, PERK, and ATF6—control the unfolded protein response (UPR), a signal transduction pathway that is triggered to restore normal physiological conditions. Buildup of misfolded proteins in ER lumen leads to a shunting of GRP78/BiP, thus triggering the UPR. PERK autophosphorylation leads to activation of ATF4, the transcription factor; finally, ATF6 activates the UPR’s target genes, including GRP78/Bip. Accordingly, the UPR is a cellular reaction to an ER stress state that, if left unchecked for an extended period, results in apoptosis and irreversible damage. The identification of caspase 4, which is in the ER and is selectively activated by apoptotic stimuli caused by reticular stress, further demonstrated the connection between reticular stress and programed cell death. Moreover, oxidative stress and ER stress are linked. Oxidative stress is brought on by elevated quantities of radical oxygen species, both mitochondrial and cytosolic, that are not under the enzymatic regulation of superoxide dismutases, whose levels fall with increasing stress. Here, we evaluated the activity of Vx-809 (Lumacaftor), a drug used in cystic fibrosis, in SH-SY5Y neuronal cells, in which an ER stress condition was induced by Thapsigargin, to verify whether the drug could improve protein folding, suggesting its possible therapeutic use in proteinopathies, such as neurodegenerative diseases (NDs). Our data show that Vx-809 is involved in the significant reduction in protein produced under ER stress, particularly in the levels of Bip, ATF4, and ATF6 by Western blotting analysis, the reduction in ROS in the cytosol and mitochondria, and the reduction in the activation of the apoptotic pathway, measured by flow cytofluorimetry analysis and in restoring calcium homeostasis. Full article

(This article belongs to the Special Issue Molecules at Play in Neurological Diseases 2024)

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12 pages, 955 KiB

Open AccessArticle

The Impact of Modern Bone Markers in Multiple Myeloma: Prospective Analyses Pre and Post-First Line Treatment

by Vlad Stefan Pop, Mihaela Iancu, Adrian Bogdan Țigu, Anda Adam, Gheorghe Tomoaia, Anca Daniela Farcas, Anca Simona Bojan and Andrada Parvu

Curr. Issues Mol. Biol. 2024, 46(9), 9330-9341; https://doi.org/10.3390/cimb46090552 - 24 Aug 2024

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Abstract

Multiple myeloma, the disease characterized by the malignant proliferation of plasma cells that invades the bone marrow, produces osteolytic lesions and secretes monoclonal proteins. Several biomarkers have been shown to represent important tools in the pathogenesis of myeloma and offer insights into bone [...] Read more.

Multiple myeloma, the disease characterized by the malignant proliferation of plasma cells that invades the bone marrow, produces osteolytic lesions and secretes monoclonal proteins. Several biomarkers have been shown to represent important tools in the pathogenesis of myeloma and offer insights into bone degradation and formation. The objectives of this current study were to assess the associations of modern biomarkers (TNF-α: tumor necrosis factor; IFN: Interferon; FreeRANKL: Free Receptor Activator for Nuclear Factor kappa B Ligand; RANKL: Receptor Activator for Nuclear Factor kappa B Ligand, Beta crosslaps, IL-6: Interleukin 6) with osteolytic lesions status after first-line treatment and to evaluate the correlations between modern and classical biomarkers (LDH: Lactate Dehydrogenase; VSH: Erythrocyte Sedimentation Rate; Hgb: Hemoglobin, Calcium, Albumin, B2microglobulin) stratified by osteolytic lesions status. A total of 35 patients diagnosed with multiple myeloma divided into two groups according to the osteolytic bone lesions, were studied: (1) unchanged status of osteolytic lesions and (2) changed status of osteolytic lesions. After fist-line treatment, we found a significant difference in Albumin (p = 0.0029) and Calcium levels (p = 0.0304), patients with a changed status in osteolytic lesions having higher values of Albumin and Calcium compared to those without changes in status of osteolytic lesions. After first-line treatment, decreased IL-6 values were significantly correlated with elevated values of Albumin (ρ = −0.96, p = 0.0005) in the patients with changed status of osteolytic lesions. Post-treatment values of IFN showed a significant positive correlation with Hemoglobin (ρ = 0.47, p = 0.0124), IL-6 (ρ = 0.55, p = 0.0026) and TNF-alpha values (ρ = 0.54, p = 0.0029). The results obtained from patients with unmodified lytic lesions identified a significant correlation between the biomarkers IL-6, Free RANKL, and IFN-beta with the classical marker LDH. This association highlights the involvement of these markers in promoting bone destruction and the development of osteolytic lesions. Full article

(This article belongs to the Special Issue Multiple Myeloma: From Molecular Mechanism to Diagnosis and Therapy)

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18 pages, 2739 KiB

Open AccessArticle

A Novel Dhillonvirus Phage against Escherichia coli Bearing a Unique Gene of Intergeneric Origin

by Anastasios Vasileiadis, Petros Bozidis, Konstantinos Konstantinidis, Nikolaos Kesesidis, Louiza Potamiti, Anna Kolliopoulou, Apostolos Beloukas, Mihalis I. Panayiotidis, Sophia Havaki, Vassilis G. Gorgoulis, Konstantina Gartzonika and Ioannis Karakasiliotis

Curr. Issues Mol. Biol. 2024, 46(9), 9312-9329; https://doi.org/10.3390/cimb46090551 - 23 Aug 2024

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Abstract

Antibiotics resistance is expanding amongst pathogenic bacteria. Phage therapy is a revived concept for targeting bacteria with multiple antibiotics resistances. In the present study, we isolated and characterized a novel phage from hospital treatment plant input, using Escherichia coli (E. coli) [...] Read more.

Antibiotics resistance is expanding amongst pathogenic bacteria. Phage therapy is a revived concept for targeting bacteria with multiple antibiotics resistances. In the present study, we isolated and characterized a novel phage from hospital treatment plant input, using Escherichia coli (E. coli) as host bacterium. Phage lytic activity was detected by using soft agar assay. Whole-genome sequencing of the phage was performed by using Next-Generation Sequencing (NGS). Host range was determined using other species of bacteria and representative genogroups of E. coli. Whole-genome sequencing of the phage revealed that Escherichia phage Ioannina is a novel phage within the Dhillonvirus genus, but significantly diverged from other Dhillonviruses. Its genome is a 45,270 bp linear double-stranded DNA molecule that encodes 61 coding sequences (CDSs). The coding sequence of CDS28, a putative tail fiber protein, presented higher similarity to representatives of other phage families, signifying a possible recombination event. Escherichia phage Ioannina lytic activity was broad amongst the E. coli genogroups of clinical and environmental origin with multiple resistances. This phage may present in the future an important therapeutic tool against bacterial strains with multiple antibiotic resistances. Full article

(This article belongs to the Section Molecular Microbiology)

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14 pages, 6572 KiB

Open AccessArticle

Cacalol Acetate as Anticancer Agent: Antiproliferative, Pro-Apoptotic, Cytostatic, and Anti-Migratory Effects

by Gareth Omar Rostro-Alonso, Alejandro Israel Castillo-Montoya, Juan Carlos García-Acosta, Erick Fernando Aguilar-Llanos, Laura Itzel Quintas-Granados, Edgar Yebrán Villegas-Vazquez, Rosario García-Aguilar, Samantha Andrea Porras-Vázquez, Lilia Patricia Bustamante-Montes, Jesús J. Alvarado-Sansininea, Manuel Jiménez-Estrada, Lizbeth Cariño-Calvo, Manuel González-del Carmen, Hernán Cortés, Gerardo Leyva-Gómez, Gabriela Figueroa-González and Octavio Daniel Reyes-Hernández

Curr. Issues Mol. Biol. 2024, 46(9), 9298-9311; https://doi.org/10.3390/cimb46090550 - 23 Aug 2024

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Abstract

Cacalol (C), a sesquiterpene isolated from Psacalium decompositum, has demonstrated anti-inflammatory and antioxidant activities. Its cytotoxic, antiproliferative, and pro-apoptotic effects have been previously shown in an in vitro breast cancer model. A derivative, cacalol acetate (CA), shows potential in regulating these processes, [...] Read more.

Cacalol (C), a sesquiterpene isolated from Psacalium decompositum, has demonstrated anti-inflammatory and antioxidant activities. Its cytotoxic, antiproliferative, and pro-apoptotic effects have been previously shown in an in vitro breast cancer model. A derivative, cacalol acetate (CA), shows potential in regulating these processes, which has not been previously reported. This study focused on an in vitro cervical cancer model, assessing CA’s antiproliferative, pro-apoptotic, cytostatic, and anti-migratory activities using the HeLa cell line. The natural anticancer agent indole-3-carbinol (I3C) was used as a control for comparison. CA demonstrated significant antitumor activities, including inhibiting cell growth, inducing apoptosis, arresting cells in the G2 phase of the cell cycle, and inhibiting cell migration. These effects were notably greater compared to I3C. I3C, while following a similar trend, did not induce Cas-3 expression, suggesting a different apoptotic pathway. Neither CA nor I3C increased p62 and LC3B levels, indicating they do not stimulate autophagy marker expression. Both compounds inhibited HeLa cell migration and induced cell cycle arrest. Despite both holding promise as anticancer agents for cervical cancer, CA’s lower cytotoxicity and stronger regulation of tumor phenotypes make it a more promising agent compared to I3C. Full article

(This article belongs to the Special Issue Phytochemicals in Cancer Chemoprevention and Treatment)

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12 pages, 431 KiB

Open AccessReview

Role of Nutrients Regulating Myeloid Derived Suppressor Cells in Cancer: A Scoping Review

by Beatriz Pérez-Peláez, Carlos Jiménez-Cortegana, Luis de la Cruz-Merino and Víctor Sánchez-Margalet

Curr. Issues Mol. Biol. 2024, 46(9), 9286-9297; https://doi.org/10.3390/cimb46090549 - 23 Aug 2024

Viewed by 238

Abstract

Myeloid-derived suppressor cells (MDSCs) are immature cells with an immunosuppressive function. MDSCs have been related to inflammation in many settings, including infections, transplantation, obesity, aging, or cancer. In oncological settings, MDSCs participate in tumor immunoescape, growth, and metastasis. Certain nutrients can modify chronic [...] Read more.

Myeloid-derived suppressor cells (MDSCs) are immature cells with an immunosuppressive function. MDSCs have been related to inflammation in many settings, including infections, transplantation, obesity, aging, or cancer. In oncological settings, MDSCs participate in tumor immunoescape, growth, and metastasis. Certain nutrients can modify chronic inflammation by their interaction with MDSCs. Therefore, the possible influence of certain nutrients on immune surveillance by their actions on MDSCs and how this may affect the prognosis of cancer patients were evaluated in this scoping review. We identified seven papers, six of which were murine model studies and only one was a human clinical trial. Globally, a significant reduction in cancer growth and progression was observed after achieving a reduction in both MDSCs and their immunosuppressive ability with nutrients such as selected vegetables, icaritin, retinoic acid, curdlan, active vitamin D, soy isoflavones, and green tea. In conclusion, the consumption of certain nutrients may have effects on MDSCs, with beneficial results not only in the prevention of tumor development and growth but also in improving patients’ response. Full article

(This article belongs to the Special Issue The Protection and Toxic Reactions of Dietary Supplements: Focusing on Molecular Mechanisms and Treatment)

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17 pages, 1341 KiB

Open AccessReview

The Role of Extracellular Vesicles in Bone Regeneration and Associated Bone Diseases

by Xinyue Wan, Wenjie Zhang, Lingyan Dai and Liang Chen

Curr. Issues Mol. Biol. 2024, 46(9), 9269-9285; https://doi.org/10.3390/cimb46090548 - 23 Aug 2024

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Abstract

Extracellular vesicles (EVs) are nanoscale particles with a lipid bilayer membrane structure secreted by various cell types. Nearly all human cells secrete EVs, primarily mediating intercellular communication. In recent years, scientists have discovered that EVs can carry multiple biological cargos, such as DNA, [...] Read more.

Extracellular vesicles (EVs) are nanoscale particles with a lipid bilayer membrane structure secreted by various cell types. Nearly all human cells secrete EVs, primarily mediating intercellular communication. In recent years, scientists have discovered that EVs can carry multiple biological cargos, such as DNA, non-coding RNAs (ncRNAs), proteins, cytokines, and lipids, and mediate intercellular signal transduction. Bone is a connective tissue with a nerve supply and high vascularization. The repair process after injury is highly complex, involving interactions among multiple cell types and biological signaling pathways. Bone regeneration consists of a series of coordinated osteoconductive and osteoinductive biological processes. As mediators of intercellular communication, EVs can promote bone regeneration by regulating osteoblast-mediated bone formation, osteoclast-mediated bone resorption, and other pathways. This review summarizes the biogenesis of EVs and the mechanisms by which EV-mediated intercellular communication promotes bone regeneration. Additionally, we focus on the research progress of EVs in various diseases related to bone regeneration. Finally, based on the above research, we explore the clinical applications of engineered EVs in the diagnosis and treatment of bone regeneration-related diseases. Full article

(This article belongs to the Special Issue Exosomes in Tissue Regeneration and Disease Therapy)

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14 pages, 3512 KiB

Open AccessArticle

Dihydroavenanthramide D Enhances Skin Barrier Function through Upregulation of Epidermal Tight Junction Expression

by Jiye Park, Jae Young Shin, Daehyun Kim, Seung-Hyun Jun, Eui Taek Jeong and Nae-Gyu Kang

Curr. Issues Mol. Biol. 2024, 46(9), 9255-9268; https://doi.org/10.3390/cimb46090547 - 23 Aug 2024

Viewed by 311

Abstract

Skin barrier dysfunction and thin epidermis are hallmarks of sensitive skin and contribute to premature aging. Avenanthramides are the primary bioactive components of colloidal oatmeal, a commonly used treatment to enhance skin barrier function. This study investigated the relationship between skin barrier function [...] Read more.

Skin barrier dysfunction and thin epidermis are hallmarks of sensitive skin and contribute to premature aging. Avenanthramides are the primary bioactive components of colloidal oatmeal, a commonly used treatment to enhance skin barrier function. This study investigated the relationship between skin barrier function and epidermal characteristics and explored the potential of dihydroavenanthramide D (dhAvD), a synthetic avenanthramide, to improve the skin barrier. We observed a significant correlation between impaired skin barrier function and decreased epidermal thickness, suggesting that a weakened barrier contributes to increased sensitivity. Our in vitro results in HaCaT cells demonstrated that dhAvD enhances keratinocyte proliferation, migration, and tight junction protein expression, thereby strengthening the skin barrier. To mimic skin barrier dysfunction, we treated keratinocytes and full-thickness skin equivalents with IL-4 and IL-13, cytokines that are implicated in atopic dermatitis, and confirmed the downregulation of tight junction and differentiation markers. Furthermore, dhAvD treatment restored the barrier function and normalized the expression of key epidermal components, such as tight junction proteins and natural moisturizing factors, in keratinocytes treated with inflammatory cytokines. In the reconstructed human skin model, dhAvD promoted both epidermal and dermal restoration. These findings suggest that dhAvD has the potential to alleviate skin sensitivity and improve skin barrier function. Full article

(This article belongs to the Section Molecular Pharmacology)

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10 pages, 1606 KiB

Open AccessArticle

Inhibitory Effects of Naringenin on LPS-Induced Skin Inflammation by NF-κB Regulation in Human Dermal Fibroblasts

by Yoon-Jung Choy, Gyu-Ri Kim and Hyung-ui Baik

Curr. Issues Mol. Biol. 2024, 46(9), 9245-9254; https://doi.org/10.3390/cimb46090546 - 23 Aug 2024

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Abstract

Flavonoids are important natural compounds characterized by their extensive biological activities. Citrus flavonoids represent a significant segment of the broader flavonoid category. Naringenin, an integral part of this series, is recognized for its powerful anti-inflammatory and antioxidant properties. In addition, considering the lack [...] Read more.

Flavonoids are important natural compounds characterized by their extensive biological activities. Citrus flavonoids represent a significant segment of the broader flavonoid category. Naringenin, an integral part of this series, is recognized for its powerful anti-inflammatory and antioxidant properties. In addition, considering the lack of existing research on naringenin’s potential effectiveness and intracellular mechanisms of action in skin-related applications, especially as a cosmetic ingredient, this study aimed to explore naringenin’s role in reducing the fundamental generation of reactive oxygen species. This was achieved by examining its inhibitory effects on the expression levels of NADPH oxidase and iNOS, ultimately leading to a reduction in NO production. This research examined the anti-inflammatory and antioxidant capacities of naringenin by employing a cellular senescence model of LPS-induced HDFs. The evaluation of naringenin’s efficacy was validated through several investigative procedures, including the NF-κB luciferase assay, ELISA assay, and qRT-PCR. To verify the anti-inflammatory effectiveness of naringenin, we measured the responsive elements of NF-κB using a luciferase reporter assay. This assessment revealed that naringenin could decrease the concentration of genes activated by NF-κB. Moreover, we found that naringenin inhibited the transcriptional expression of known NF-κB-regulated inflammatory cytokines, including IL-1β, IL-6, and IL-8. In addition, results from the qRT-PCR analysis indicated that naringenin facilitated a reduction in iNOS expression. Based on the data gathered and analyzed in this study, it can be conclusively inferred that naringenin possesses promising potential as a cosmetic ingredient, offering both anti-inflammatory and antioxidant benefits. Full article

(This article belongs to the Special Issue The Role of Bioactives in Inflammation)

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Curr. Issues Mol. Biol., Volume 46, Issue 9 (September 2024) – 18 articles

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