Current Issues in Molecular Biology

17 pages, 5639 KiB

Open AccessArticle

Comprehensive Transcriptomic and Physiological Insights into the Response of Root Growth Dynamics During the Germination of Diverse Sesame Varieties to Heat Stress

by Xiaoyu Su, Chunming Li, Yongliang Yu, Lei Li, Lina Wang, Dandan Lu, Yulong Zhao, Yao Sun, Zhengwei Tan and Huizhen Liang

Curr. Issues Mol. Biol. 2024, 46(12), 13311-13327; https://doi.org/10.3390/cimb46120794 - 22 Nov 2024

Abstract

Heat stress constitutes a serious threat to sesame (Sesamum indicum L.). Root development during seed germination plays an essential role in plant growth and development. Nevertheless, the regulatory mechanisms underlying heat stress remain poorly understood. In this study, two sesame varieties differing [...] Read more.

Heat stress constitutes a serious threat to sesame (Sesamum indicum L.). Root development during seed germination plays an essential role in plant growth and development. Nevertheless, the regulatory mechanisms underlying heat stress remain poorly understood. In this study, two sesame varieties differing in leaf heat tolerance (Zheng Taizhi 3 (heat-tolerant) and SP19 (heat-sensitive)) have been employed to investigate the impact of heat stress on root growth during germination. The results showed that heat stress significantly reduced the radicle length by 35.71% and 67.02% in Zheng Taizhi 3 and SP19, respectively, while germination rates remained unchanged. In addition, heat stress induced oxidative stress, as evidenced by increased reactive oxygen species (ROS) production, malondialdehyde (MDA) content, and reduced indole-3-acetic acid (IAA) content, accompanied by enhanced antioxidant enzyme activities, including those of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT), and the abscisic acid (ABA) content significantly increased in both varieties. However, the oxidation resistance in the roots of Zheng Taizhi 3 was enhanced compared to that of SP19 under heat stress, while IAA production was maintained and ABA content was reduced. A comparative transcriptome analysis identified 6164 and 6933 differentially expressed genes (DEGs) in Zheng Taizhi 3 and SP19, respectively, with 4346 overlapping DEGs. These DEGs included those related to stress tolerance, such as heat-shock proteins (HSPs), the antioxidant defense system, hormone signal transduction, and the biosynthetic pathway of phenylpropanoid. These findings provide insights into the physiological and molecular mechanisms underlying the adaptation of sesame to heat stress, which could inform breeding strategies for developing heat-tolerant sesame varieties. Full article

(This article belongs to the Special Issue Advances in Multi-Omics for Functional Genomics Studies and Molecular Breeding)

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15 pages, 8165 KiB

Open AccessArticle

Multiomics Analysis of Molecules Associated with Cancer in Mesenchymal-Stem-Cell-(MSC)-Derived Exosome-Treated Hepatocellular Carcinoma Cells

by Wen-Yong Gao, Chantana Boonyarat, Nutjakorn Samar, Benjabhorn Sethabouppha and Pornthip Waiwut

Curr. Issues Mol. Biol. 2024, 46(12), 13296-13310; https://doi.org/10.3390/cimb46120793 - 21 Nov 2024

Abstract

Hepatocellular carcinoma (HCC) is the most common form of liver cancer in humans, with an increasing incidence worldwide. The current study aimed to explore the molecular mechanisms that inhibit the proliferation of HepG2 cells, a hepatoblastoma-derived cell line. MSC-derived exosomes (UC-MSCs) were prepared [...] Read more.

Hepatocellular carcinoma (HCC) is the most common form of liver cancer in humans, with an increasing incidence worldwide. The current study aimed to explore the molecular mechanisms that inhibit the proliferation of HepG2 cells, a hepatoblastoma-derived cell line. MSC-derived exosomes (UC-MSCs) were prepared with a median particle size (N50) of 135.8 nm. Concentrations of UC-MSCs ranging from 10 μg/mL to 1000 μg/mL were applied to HepG2 cell cultures and compared to untreated and anticancer drug-treated HepG2 cells. A combined approach was employed, integrating a proteomic analysis of UC-MSCs, metabolomic analysis of HepG2 cells, and transcriptomic profiling of HepG2 cells to decipher the inhibitory mechanisms of UC-MSC exosomes on HepG2 cell growth. Treatment with a high concentration of UC-MSCs led to a notable reduction in HepG2 cell viability, with survival decreasing by 65%. A proteomic analysis of UC-MSCs revealed enriched degranulation processes in Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, in addition to the known exosomal pathways. Transcriptomic profiling showed distinct changes in the expression of genes related to hepatocellular diseases in UC-MSC-treated HepG2 cells, contrasting with changes observed in HepG2 cells treated with the chemotherapeutic agent doxorubicin (DOX). Combined with a metabolomic analysis, the detailed GO and KEGG pathway analyses indicated that pathways associated with neutrophil extracellular trap formation played a critical role in mediating protein degradation and suppressing central carbon metabolism in cancer cells. Our results revealed that the UC-MSC treatment mimicked molecular mechanisms similar to those involved in neutrophil extracellular trap formation, exhibiting effects on HepG2 cell growth suppression that differed from those of chemical cancer drugs. Notably, the UC-MSC treatment demonstrated that protein degradation in HepG2 cells was regulated through canonical signaling pathways activated by bacterial peptides in neutrophils. This research has provided valuable insights into the potential of MSC-derived exosomes as a therapeutic approach for cancer treatment in the future. Full article

(This article belongs to the Special Issue Metabolic Reprogramming of Immune Cells in Tumor Microenvironment)

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15 pages, 1097 KiB

Open AccessReview

Differentiation of Human Mesenchymal Stem Cells into Corneal Epithelial Cells: Current Progress

by Abdul Malik Setiawan and Taty Anna Kamarudin

Curr. Issues Mol. Biol. 2024, 46(12), 13281-13295; https://doi.org/10.3390/cimb46120792 - 21 Nov 2024

Abstract

The limited availability of corneal tissue grafts poses significant challenges in the treatment of corneal blindness. Novel treatment utilizes stem cell grafts transplanted from the healthy side of the cornea to the damaged side. However, this procedure is only possible for those who [...] Read more.

The limited availability of corneal tissue grafts poses significant challenges in the treatment of corneal blindness. Novel treatment utilizes stem cell grafts transplanted from the healthy side of the cornea to the damaged side. However, this procedure is only possible for those who have one-sided corneal blindness. Human stem cells offer promising potential for corneal tissue engineering, providing an alternative solution. Among the different types of stem cells, mesenchymal stem cells (MSCs) stand out due to their abundance and ease of isolation. Human MSCs can be derived from bone marrow, adipose, and umbilical cord tissues. Differentiating MSC toward corneal tissue can be achieved through several methods including chemical induction and co-culture with adult corneal cells such as human limbal epithelial stem cells (LESCs) and human corneal epithelial cells (hTCEpi). Adipose-derived stem cells (ADSCs) are the most common type of MSC that has been studied for corneal differentiation. Corneal epithelial cells are the most common corneal cell type targeted by researchers for corneal differentiation. Chemical induction with small molecules, especially bone morphogenetic protein 4 (BMP4), all-trans retinoic acid (ATRA), and epidermal growth factor (EGF), has gained more popularity in corneal epithelial cell differentiation. This review highlights the current progress in utilizing MSCs for corneal differentiation studies, showcasing their potential to revolutionize treatments for corneal blindness. Full article

(This article belongs to the Special Issue The Contribution and Application of Molecular Biology in the Applied Biosciences — Focusing on Medicine, Biomaterials and Tissue Engineering Fields)

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14 pages, 1727 KiB

Open AccessArticle

The Potential Association of CDKN2A and Ki-67 Proteins in View of the Selected Characteristics of Patients with Head and Neck Squamous Cell Carcinoma

by Dariusz Nałęcz, Agata Świętek, Dorota Hudy, Zofia Złotopolska, Michał Dawidek, Karol Wiczkowski and Joanna Katarzyna Strzelczyk

Curr. Issues Mol. Biol. 2024, 46(11), 13267-13280; https://doi.org/10.3390/cimb46110791 - 20 Nov 2024

Abstract

Head and neck squamous cell carcinoma (HNSCC) is the sixth most prevalent type of cancer worldwide. Not all mechanisms associated with cell cycle disturbances have been recognized in HNSCC. The aim of this study was to examine the concentration of CDKN2A and Ki-67 [...] Read more.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most prevalent type of cancer worldwide. Not all mechanisms associated with cell cycle disturbances have been recognized in HNSCC. The aim of this study was to examine the concentration of CDKN2A and Ki-67 proteins in 54 tumor and margin samples of HNSCC and to evaluate their association with the clinical and demographic variables. The ELISA method was used to measure concentrations of CDKN2A and Ki-67 in the tissue homogenates. A significantly higher CDKN2A concentration was found in OSCC tumor samples as compared with OPSCC+HPSCC+LSCC. An inverse correlation was observed for Ki-67. We showed an association between the CDKN2A level and the clinical parameters N in tumors. The patients with concomitant diseases had significantly higher levels of Ki-67 as compared with patients with no concomitant diseases. An analysis of the effect of drinking habits on Ki-67 level demonstrated a statistical difference between regular or occasional users of stimulants and patients who do not use any stimulants in the tumor and margin samples. Moreover, we found an association between CDKN2A and Ki-67 concentrations and the HPV status in tumor and margin samples. The levels of the proteins tested may be dependent on environmental factors. Our results showed that changes in protein levels in HNSCC subtypes may reflect different molecular pathways of tumor development or may also be responsible for the involvement of CDKN2A and Ki-67 in the carcinogenesis process. Full article

(This article belongs to the Special Issue Oral Cancer: Prophylaxis, Etiopathogenesis and Treatment)

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15 pages, 2867 KiB

Open AccessArticle

RNA Splicing Aberrations in Hereditary Cancer: Insights from Turkish Patients

by Seda Kilic, Ozge Sukruoglu Erdogan, Seref Bugra Tuncer, Betul Celik Demirbas, Zubeyde Yalniz Kayim and Hulya Yazici

Curr. Issues Mol. Biol. 2024, 46(11), 13252-13266; https://doi.org/10.3390/cimb46110790 - 20 Nov 2024

Abstract

The process of RNA splicing is fundamental in contributing to proteomic diversity and regulating gene expression. Dysregulation of splicing is associated with various human disorders, including cancer. Through functional studies, this study sought to examine the potential impact of seven variants within six [...] Read more.

The process of RNA splicing is fundamental in contributing to proteomic diversity and regulating gene expression. Dysregulation of splicing is associated with various human disorders, including cancer. Through functional studies, this study sought to examine the potential impact of seven variants within six inherited cancer-related genes on RNA splicing patterns in Turkish cancer patients. Upon detecting variants using Next-Generation Sequencing (NGS), we used Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) and Sanger sequencing to elucidate the effects of these variants on splicing. Three of the seven variants demonstrated no discernible effect on RNA, while four exhibited pathogenic characteristics. Specifically, the variants APC c.532-1G>A rs1554072547, BRCA1c.4358-3A>G rs1567779966, BRCA2c.7436-1G>C rs81002830 and MSH3c.1897-1G>A rs1744149615 were identified as pathogenic, while the variants BLMc.4076+4T>G rs183176301, RB1c.2489+2T>C rs1555294636 and RB1c.1050-2A>G rs? were found to be benign from a splicing perspective. These findings highlight the importance of verifying the precise consequences of splice-site variants through experimental analysis, given their potential implications for genetic disorders and cancer predisposition. This research contributes to the understanding of splice-site variants in inherited cancer predisposition, particularly among Turkish cancer patients. It emphasizes the necessity for further exploration into the mechanisms and functional consequences of alternative splicing for potential therapeutic interventions in cancer. Full article

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

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29 pages, 3076 KiB

Open AccessReview

A Comprehensive Review on Bioactive Molecules and Advanced Microorganism Management Technologies

by Adil Farooq Wali, Sirajunisa Talath, Sathvik B. Sridhar, Javedh Shareef, Manjunatha Goud, Imran Rashid Rangraze, Nowar Nizar Alaani and Omnia Ibrahim Mohamed

Curr. Issues Mol. Biol. 2024, 46(11), 13223-13251; https://doi.org/10.3390/cimb46110789 - 20 Nov 2024

Abstract

The advent of new strains of resistant microbes and the concomitant growth in multidrug resistance have made antimicrobial resistance an urgent public health concern. New antimicrobials are desperately needed to boost the success rates of treating infectious diseases and save lives. There are [...] Read more.

The advent of new strains of resistant microbes and the concomitant growth in multidrug resistance have made antimicrobial resistance an urgent public health concern. New antimicrobials are desperately needed to boost the success rates of treating infectious diseases and save lives. There are many intriguing biomolecules with antibacterial action, which are mostly unexplored in microorganisms. This review article describes the importance of natural compounds against microorganisms using advanced techniques to protect individuals from diseases. We have conducted an extensive literature review using databases such as SCOPUS, SCI, PUBMED, ScienceDirect, and Medline to gather relevant information. Our review covers various microorganism sources for antimicrobials, antifungal drugs, micro-culturing techniques, and microbial-based microsystems’ applications. Every kind of higher trophic life depends on microorganisms for sustenance. The unseen majority is essential to understanding how humans and other living forms can survive anthropogenic climate change. The article discusses antimicrobial substances and the latest techniques and strategies for developing effective treatments. Novel model systems and cutting-edge biomolecular and computational methodologies could help researchers enhance antimicrobial resistance by completely capitalizing on lead antimicrobials. Full article

(This article belongs to the Special Issue Therapeutic Effects of Natural Bioactive Compounds in the Management of Human Diseases)

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15 pages, 4188 KiB

Open AccessArticle

A Set of Proximal Regulatory Elements Contribute to the Transcriptional Activity of the Human Lipoprotein Lipase Promoter

by Nasmah K. Bastaki, Taybha A. Albarjes, Afnan K. Mohamed, Noorhan H. Sabri and Suzanne A. Al-Bustan

Curr. Issues Mol. Biol. 2024, 46(11), 13209-13222; https://doi.org/10.3390/cimb46110788 - 18 Nov 2024

Abstract

Lipoprotein lipase (LPL) is a multifunctional protein that catalyzes the hydrolysis of plasma triglycerides, releasing free fatty acids, which play critical roles in the metabolism and transport of lipids. The transcription of LPL in response to cell types and regulatory factors is a [...] Read more.

Lipoprotein lipase (LPL) is a multifunctional protein that catalyzes the hydrolysis of plasma triglycerides, releasing free fatty acids, which play critical roles in the metabolism and transport of lipids. The transcription of LPL in response to cell types and regulatory factors is a complex process that starts with its promoter. In previous studies, several proximal regulatory elements within the human LPL promoter were individually characterized. This study was designed to characterize the effect of 12 proximal regulatory elements as a combined unit on the transcriptional activity of the LPL promoter. The hypothesis was that these proximal regulatory elements collectively result in the optimal transcriptional activity of the human LPL promoter. Full and partial LPL promoter sequences, which contained and excluded the 12 regulatory elements, respectively, were cloned and inserted into a promoterless luciferase reporter vector. The functional activities of these constructs were tested in vitro using a dual-luciferase reporter assay. Our results showed that HEK-293 cells transfected with the full LPL promoter exhibited significantly greater luciferase activity than cells transfected with partial LPL promoters. Our results indicate that the proximal regulatory elements within the LPL promoter, including four TATA boxes, two Oct-1 sites, one CT element, two C/EBPα sites, one SP1 site, and two cis-acting regions (LP-α and LP-β), are essential for its transcriptional activity. Full article

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

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16 pages, 2267 KiB

Open AccessArticle

Ornamental Barberry Twigs as an Underexploited Source of Berberine-Rich Extracts—Preliminary Research

by Michał Miłek, Małgorzata Dżugan, Natalia Pieńkowska, Sabina Galiniak, Mateusz Mołoń and Wojciech Litwińczuk

Curr. Issues Mol. Biol. 2024, 46(11), 13193-13208; https://doi.org/10.3390/cimb46110787 - 18 Nov 2024

Abstract

Berberine is a natural substance obtained from the roots of common barberry which, due to its strong pharmacological activity, is a commonly tested ingredient of dietary supplements. However, ornamental barberries, which are widely available, have not been considered as a source of berberine [...] Read more.

Berberine is a natural substance obtained from the roots of common barberry which, due to its strong pharmacological activity, is a commonly tested ingredient of dietary supplements. However, ornamental barberries, which are widely available, have not been considered as a source of berberine so far. The research aimed to check whether the ornamental barberry leaves and twigs could be used as an easily accessible raw material for obtaining natural berberine-rich extract with biological activity. Twigs and leaves of seven cultivars of ornamental barberry extracts were assessed for their polyphenol content, antioxidant potential (FRAP and DPPH), and berberine content using high-performance thin layer chromatography (HPTLC). As a reference, commercially available roots of Berberis vulgaris were used. For the next step, selected extracts (two with high and two with low berberine content) were tested on three cell lines (HaCaT, A375, Caco-2) using neutral red assay, and pure berberine sulfate (1–100 μg mL⁻¹) was used as a control. Although the antioxidant potential of aqueous–methanol extracts of tested barberry was higher for the leaves than for the twigs, the berberine content was determined only in the twig extracts (from 42 to 676 mg 100 g⁻¹). Studies on cell lines have shown the general toxicity of barberry extracts, but the observed effect was not directly correlated with the content of the alkaloid. However, the extract showed greater activity compared to an analogous dose of pure berberine, suggesting a significant effect of the matrix composition. For the first time, it was shown that the twigs of selected cultivars of ornamental barberry can be considered as a promising berberine source for the pharmaceutical industry to develop new effective formulations. However, these findings require further studies. Full article

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

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14 pages, 2127 KiB

Open AccessArticle

Characterization of Trileucine Motif in the C-Terminus of the Equine Lutropin/Choriogonadotropin Receptor

by Sang-Gwon Kim, Munkhzaya Byambaragchaa, Sei Hyen Park, Ha-Rin Jeong, Jae-Hyek Park, Myung-Hum Park, Myung-Hwa Kang and Kwan-Sik Min

Curr. Issues Mol. Biol. 2024, 46(11), 13179-13192; https://doi.org/10.3390/cimb46110786 - 18 Nov 2024

Abstract

The lutropin/chorionic gonadotropin receptor (LH/CGR) belongs to the G protein-coupled receptor family, characterized by conserved leucine residues in their carboxyl-terminal cytoplasmic tails. This study aimed to investigate the functional significance of the equine LH/CGR (eLH/CGR) trileucine motif in signal transduction. Wild-type eLH/CGR (eLH/CGR-wt) [...] Read more.

The lutropin/chorionic gonadotropin receptor (LH/CGR) belongs to the G protein-coupled receptor family, characterized by conserved leucine residues in their carboxyl-terminal cytoplasmic tails. This study aimed to investigate the functional significance of the equine LH/CGR (eLH/CGR) trileucine motif in signal transduction. Wild-type eLH/CGR (eLH/CGR-wt) and mutant receptors, in which the trileucine motif was altered to alanine (eLH/CGR-ALL, LAL, LLA, and AAA), were analyzed in transfected cells. The expression levels of mutants ranged from 60% to 78%, with eLH/CGR-AAA showing the lowest level. Although the trileucine motif did not individually affect cAMP responsiveness, the combined mutant (eLH/CGR-AAA) significantly reduced cAMP response, surface receptor levels and enhanced receptor internalization rates. Activation of phospho-ERK1/2 was rapid in all mutants, peaking at 5 min, but eLH/CGR-ALL and LAL mutants exhibited a sharp decline in activity at 15 min. Notably, the eLH/CGR-LLA and AAA mutants showed similar phospho-ERK1/2 activity as the wild type. The eLH/CGR-AAA mutant also displayed a two-fold reduction in PKA signal transduction. These findings suggest that while individual leucine residues of the trileucine motif do not affect cAMP responsiveness, the entire motif plays a crucial role in receptor trafficking and signaling, specifically influencing PKA and phospho-ERK1/2 pathways. Full article

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

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14 pages, 3641 KiB

Open AccessArticle

Bacterial Diversity, Metabolic Profiling, and Application Potential of Antarctic Soil Metagenomes

by Mario Fernández, Salvador Barahona, Fernando Gutierrez, Jennifer Alcaíno, Víctor Cifuentes and Marcelo Baeza

Curr. Issues Mol. Biol. 2024, 46(11), 13165-13178; https://doi.org/10.3390/cimb46110785 - 18 Nov 2024

Abstract

Antarctica has attracted increasing interest in understanding its microbial communities, metabolic potential, and as a source of microbial hydrolytic enzymes with industrial applications, for which advances in next-generation sequencing technologies have greatly facilitated the study of unculturable microorganisms. In this work, soils from [...] Read more.

Antarctica has attracted increasing interest in understanding its microbial communities, metabolic potential, and as a source of microbial hydrolytic enzymes with industrial applications, for which advances in next-generation sequencing technologies have greatly facilitated the study of unculturable microorganisms. In this work, soils from seven sub-Antarctic islands and Union Glacier were studied using a whole-genome shotgun metagenomic approach. The main findings were that the microbial community at all sites was predominantly composed of the bacterial phyla Actinobacteria and Cyanobacteria, and the families Streptomycetaceae and Pseudonocardiaceae. Regarding the xenobiotic biodegradation and metabolism pathway, genes associated with benzoate, chloroalkane, chloroalkene, and styrene degradation were predominant. In addition, putative genes encoding industrial enzymes with predicted structural properties associated with improved activity at low temperatures were found, with catalases and malto-oligosyltrehalose trehalohydrolase being the most abundant. Overall, our results show similarities between soils from different Antarctic sites with respect to more abundant bacteria and metabolic pathways, especially at higher classification levels, regardless of their geographic location. Furthermore, our results strengthen the potential of Antarctic soils as a source of industrially relevant enzymes. Full article

(This article belongs to the Special Issue Bioinformatics Research in Bacterial Genomics, Metagenomics and Metatranscriptomics)

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14 pages, 4679 KiB

Open AccessArticle

miR-5100 Overexpression Inhibits Prostate Cancer Progression by Inducing Cell Cycle Arrest and Targeting E2F7

by An Zhang, Wen Deng, Haojie Shang, Jian Wu, Yucong Zhang, Qianyuan Zhuang, Cuntai Zhang and Yuan Chen

Curr. Issues Mol. Biol. 2024, 46(11), 13151-13164; https://doi.org/10.3390/cimb46110784 - 18 Nov 2024

Abstract

Despite advances in treatment, prostate cancer remains a leading cause of cancer-related deaths among men, highlighting the urgent need for innovative therapeutic strategies. MicroRNAs (miRNAs) have emerged as key regulatory molecules in cancer biology. In this research, we investigated the tumor-suppressive role of [...] Read more.

Despite advances in treatment, prostate cancer remains a leading cause of cancer-related deaths among men, highlighting the urgent need for innovative therapeutic strategies. MicroRNAs (miRNAs) have emerged as key regulatory molecules in cancer biology. In this research, we investigated the tumor-suppressive role of miR-5100 in PCa and its underlying molecular mechanism. By using RT-qPCR, we observed lower miR-5100 expression in PCa cell lines than in benign prostate cells. Functional assays demonstrated that miR-5100 overexpression significantly suppressed PCa cell proliferation, migration, and invasion. By using RNA-sequencing, we identified 446 down-regulated and 806 upregulated candidate miR-5100 target genes overrepresenting cell cycle terms. Mechanistically, E2F7 was confirmed as a direct target of miR-5100 using the reporter gene assay and RIP assay. By conducting flow cytometry analysis, cell cycle progression was blocked at the S phase. E2F7 overexpression partially mitigated the suppressive impact of miR-5100 in PCa cells. In conclusion, miR-5100 is a tumor suppressor in PCa by blocking cell cycle and targeting E2F7. Full article

(This article belongs to the Special Issue Molecular Research of Urological Diseases)

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20 pages, 1429 KiB

Open AccessReview

Pharmacological and Biological Targeting of FGFR1 in Cancer

by Shuai Fan, Yuxin Chen, Wenyu Wang, Wanting Xu, Mei Tian, Yuetong Liu, Yutong Zhou, Dan Liu, Qin Xia and Lei Dong

Curr. Issues Mol. Biol. 2024, 46(11), 13131-13150; https://doi.org/10.3390/cimb46110783 - 18 Nov 2024

Abstract

FGFR1 is a key member of the fibroblast growth factor receptor family, mediating critical signaling pathways such as RAS-MAPK and PI3K-AKT. which are integral to regulating essential cellular processes, including proliferation, differentiation, and survival. Alterations in FGFR1 can lead to constitutive activation of [...] Read more.

FGFR1 is a key member of the fibroblast growth factor receptor family, mediating critical signaling pathways such as RAS-MAPK and PI3K-AKT. which are integral to regulating essential cellular processes, including proliferation, differentiation, and survival. Alterations in FGFR1 can lead to constitutive activation of signaling pathways that drive oncogenesis by promoting uncontrolled cell division, inhibiting apoptosis, and enhancing the metastatic potential of cancer cells. This article reviews the activation mechanisms and signaling pathways of FGFR1 and provides a detailed exposition of the types of FGFR1 aberration. Furthermore, we have compiled a comprehensive overview of current therapies targeting FGFR1 aberration in cancer, aiming to offer new perspectives for future cancer treatments by focusing on drugs that address specific FGFR1 alterations. Full article

(This article belongs to the Section Molecular Medicine)

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12 pages, 9628 KiB

Open AccessArticle

Selenized Yeast Protects Against Cadmium-Induced Follicular Atresia in Laying Hens by Reducing Autophagy in Granulosa Cells

by Caimei Wu, Yuxuan Jiang, Ziyun Zhou, Yuwei Zhang, Yixuan Zhou, Shiping Bai, Jian Li, Fali Wu, Jianping Wang and Yang Lyu

Curr. Issues Mol. Biol. 2024, 46(11), 13119-13130; https://doi.org/10.3390/cimb46110782 - 18 Nov 2024

Abstract

Cadmium (Cd) exposure can induce follicular atresia and laying performance reduction in hens, which is linked to autophagy within the granulosa cells. Selenium (Se) can influence autophagy and counteract Cd toxicity. This study aimed to investigate the protective effect of Se on Cd-induced [...] Read more.

Cadmium (Cd) exposure can induce follicular atresia and laying performance reduction in hens, which is linked to autophagy within the granulosa cells. Selenium (Se) can influence autophagy and counteract Cd toxicity. This study aimed to investigate the protective effect of Se on Cd-induced follicular atresia in laying hens. Sixty-four laying hens were randomly allocated into 4 treatments: control group: basal diet; Se group: basal diet + 0.4 mg/kg Se from selenized yeast; Cd group: basal diet + 25 mg/kg Cd from CdCl₂; and Cd+Se group: basal diet + 25 mg/kg Cd + 0.4 mg/kg Se. Compared to the Cd group, Se supplementation alleviated the ovarian pathological changes and oxidative stress in the follicles, serum, liver, and ovary, increased daily laying production, ovarian weight and F5–F1 follicle amounts, serum levels of progesterone and oestradiol, and up-regulated mTOR expression (p < 0.05), while decreasing the count of autophagic vacuoles, ovarian atresia follicle numbers, and Cd deposition, and down-regulated expression levels of autophagy-related mRNAs, including ATG5, LC3-I, and LC3-II, Beclin1, and Dynein in the follicles (p < 0.05). In conclusion, 0.4 mg/kg Se supplementation protected against Cd-induced laying performance reduction and follicular atresia, which were achieved via decreasing oxidative stress and inhibiting mTOR pathways of autophagy. Full article

(This article belongs to the Special Issue Molecular Research in Food Science)

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14 pages, 3021 KiB

Open AccessArticle

Transmembrane-4 L-Six Family Member-1 Is Essential for Embryonic Blood Vessel Development

by Chi-Iou Lin, Anne Merley, Hiromi Wada, Jianwei Zheng and Shou-Ching S. Jaminet

Curr. Issues Mol. Biol. 2024, 46(11), 13105-13118; https://doi.org/10.3390/cimb46110781 - 18 Nov 2024

Abstract

Transmembrane-4 L-six family member-1 (TM4SF1) is a small cell surface glycoprotein that is highly and selectively expressed on endothelial cell and mesenchymal stem cell surfaces. TM4SF1 regulates cellular functions by forming protein complexes called TMED (TM4SF1-enriched microdomains) that either recruit growth-factor activated proteins [...] Read more.

Transmembrane-4 L-six family member-1 (TM4SF1) is a small cell surface glycoprotein that is highly and selectively expressed on endothelial cell and mesenchymal stem cell surfaces. TM4SF1 regulates cellular functions by forming protein complexes called TMED (TM4SF1-enriched microdomains) that either recruit growth-factor activated proteins and internalize them via microtubules to distribute the recruited molecules intracellularly or support the formation of nanopodia for intercellular interactions extracellularly. Through a genetically manipulated mouse model for global Tm4sf1 gene knockout, we demonstrate here that TM4SF1 is essential for blood vessel development. Tm4sf1-null embryos fail to develop blood vessels and experience lethality at E9.5. Tm4SF1-heterozygous embryos are smaller in body size during early embryonic development, and almost half die in utero due to intracranial hemorrhage in the intraventricular and subarachnoid space, which becomes apparent by E17.5. Surviving Tm4SF1-heterozygotes do not display overt phenotypic differences relative to wild type littermates postnatally. Together, these studies demonstrate that TM4SF1, through its molecular facilitator and nanopodia formation roles in TMED, intimately regulates blood vessel formation during embryonic development. Full article

(This article belongs to the Special Issue Cerebrovascular Diseases: From Pathogenesis to Treatment)

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27 pages, 6680 KiB

Open AccessReview

Extracellular Vesicles: A Novel Diagnostic Tool and Potential Therapeutic Approach for Equine Osteoarthritis

by Mohamed I. Elashry, Julia Speer, Isabelle De Marco, Michele C. Klymiuk, Sabine Wenisch and Stefan Arnhold

Curr. Issues Mol. Biol. 2024, 46(11), 13078-13104; https://doi.org/10.3390/cimb46110780 - 17 Nov 2024

Abstract

Osteoarthritis (OA) is a chronic progressive degenerative joint disease that affects a significant portion of the equine population and humans worldwide. Current treatment options for equine OA are limited and incompletely curative. Horses provide an excellent large-animal model for studying human OA. Recent [...] Read more.

Osteoarthritis (OA) is a chronic progressive degenerative joint disease that affects a significant portion of the equine population and humans worldwide. Current treatment options for equine OA are limited and incompletely curative. Horses provide an excellent large-animal model for studying human OA. Recent advances in the field of regenerative medicine have led to the exploration of extracellular vesicles (EVs)—cargoes of microRNA, proteins, lipids, and nucleic acids—to evaluate their diagnostic value in terms of disease progression and severity, as well as a potential cell-free therapeutic approach for equine OA. EVs transmit molecular signals that influence various biological processes, including the inflammatory response, apoptosis, proliferation, and cell communication. In the present review, we summarize recent advances in the isolation and identification of EVs, the use of their biologically active components as biomarkers, and the distribution of the gap junction protein connexin 43. Moreover, we highlight the role of mesenchymal stem cell-derived EVs as a potential therapeutic tool for equine musculoskeletal disorders. This review aims to provide a comprehensive overview of the current understanding of the pathogenesis, diagnosis, and treatment strategies for OA. In particular, the roles of EVs as biomarkers in synovial fluid, chondrocytes, and plasma for the early detection of equine OA are discussed. Full article

(This article belongs to the Special Issue Latest Review Papers in Molecular Biology 2024)

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20 pages, 2043 KiB

Open AccessArticle

Differences in Plasma Extracellular Vesicles of Different Origin in On-Pump Versus Off-Pump Cardiac Surgery

by Arthur Aquino, Napisat Abutalimova, Yi Ma, Imran Ismail-zade, Vadim Grebennik, Artem Rubinstein, Igor Kudryavtsev, Ekatherina Zaikova, Darina Sambur, Alexander Marichev, Olga Kalinina, Andrey Bautin, Anna Kostareva, Jarle Vaage and Alexey Golovkin

Curr. Issues Mol. Biol. 2024, 46(11), 13058-13077; https://doi.org/10.3390/cimb46110779 - 17 Nov 2024

Abstract

Coronary artery bypass grafting (CABG) using cardiopulmonary bypass (CPB) causes a systemic inflammatory response that can worsen patient outcomes. Off-pump surgery has been associated with a reduced inflammatory response. The precise mechanisms and the role of extracellular vesicles (EVs) in this context are [...] Read more.

Coronary artery bypass grafting (CABG) using cardiopulmonary bypass (CPB) causes a systemic inflammatory response that can worsen patient outcomes. Off-pump surgery has been associated with a reduced inflammatory response. The precise mechanisms and the role of extracellular vesicles (EVs) in this context are not fully understood. This study aimed to investigate the early immune response, including main T- and B-lymphocyte subsets, cytokine profiles, and plasma EVs, in patients undergoing off-pump (n = 18) and on-pump (n = 18) CABG. Thirty-six patients undergoing isolated CABG were enrolled in this randomized control study. Pre- and 24 h postoperative blood samples were analyzed for immune cell populations, cytokine levels, and plasma EV phenotyping. Off-pump CABG triggered a milder immune response than on-pump surgery. On-pump surgery led to greater changes in circulating EVs, particularly platelet- (CD62P+), endothelial- (CD31+), and B-cell-derived (CD19+), as well as platelet- and erythrocyte-derived aggregates (CD41+CD235a+). Levels of platelet-derived EVs, expressing both constitutional and activation markers (CD41+CD62P+) decreased in both groups of patients 24 h after surgery. On-pump cardiac procedures led to an increase in T-regulatory cell-derived EVs (CD73+CD39+), suggesting a potential mechanism for immune suppression compared to off-pump surgery. There were numerous correlations between EV levels and cytokine profiles following on-pump surgery, hinting at a close relationship. Leucocyte-derived EVs exhibited positive correlations with each other and with GRO but showed negative correlations with endothelial-derived EVs (CD90+ and CD31+). Additionally, CD73+ EVs demonstrated positive correlations with platelet counts and with erythrocyte-derived CD235a+ EVs. EV changes were significantly greater after on-pump surgery, highlighting a more pronounced response to this type of surgery and emphasizing the role of EVs as regulators of post-surgical inflammation. Full article

(This article belongs to the Section Molecular Medicine)

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8 pages, 1339 KiB

Open AccessBrief Report

Optimized Protocol for RNA Isolation from Penicillium spp. and Aspergillus fumigatus Strains

by Aleksandra Siniecka-Kotula, Martyna Mroczyńska-Szeląg, Anna Brillowska-Dąbrowska and Lucyna Holec-Gąsior

Curr. Issues Mol. Biol. 2024, 46(11), 13050-13057; https://doi.org/10.3390/cimb46110778 - 17 Nov 2024

Abstract

Efficient RNA isolation from filamentous fungi is crucial for gene expression studies, but it poses significant technical challenges due to the robust cell walls and susceptibility of RNA to degradation by ribonucleases. This study presents the effectiveness of two RNA isolation protocols for [...] Read more.

Efficient RNA isolation from filamentous fungi is crucial for gene expression studies, but it poses significant technical challenges due to the robust cell walls and susceptibility of RNA to degradation by ribonucleases. This study presents the effectiveness of two RNA isolation protocols for four species of filamentous fungi: Penicillium crustosum, Penicillium rubens, Penicillium griseofulvum, and Aspergillus fumigatus. Both protocols utilized Fenzol Plus for cell lysis but varied in the mechanical disruption methods: bead-beating versus manual vortexing. The results show that the bead-beater method (Protocol 1) yielded significantly higher RNA quantities, with better purity and integrity, as demonstrated by higher A260/A280 and A260/A230 ratios. RNA concentrations ranged from 30 to 96 µg/g of dry biomass in Penicillium species and up to 52 µg/g in A. fumigatus. The use of chloroform in Protocol 1 also enhanced RNA purity, effectively separating contaminants such as DNA, proteins, and polysaccharides. This optimized protocol is highly efficient and can be applied in routine laboratories handling large numbers of fungal samples, making it a robust method for downstream applications such as cDNA synthesis and transcriptome analysis. Full article

(This article belongs to the Section Molecular Microbiology)

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15 pages, 1932 KiB

Open AccessArticle

Oxysophocarpine Prevents the Glutamate-Induced Apoptosis of HT–22 Cells via the Nrf2/HO–1 Signaling Pathway

by Ruiying Yuan, Dan Gao, Guibing Yang, Dongzhi Zhuoma, Zhen Pu, Yangzhen Ciren, Bin Li and Jianqing Yu

Curr. Issues Mol. Biol. 2024, 46(11), 13035-13049; https://doi.org/10.3390/cimb46110777 - 16 Nov 2024

Abstract

Oxysophocarpine (OSC), a quinolizidine alkaloid, shows neuroprotective potential, though its mechanisms are unclear. The aim of the present study was to investigate the neuroprotective effects of OSC through the nuclear factor erythroid 2−related factor 2 (Nrf2)/ heme oxygenase−1 (HO–1) signaling pathway using the [...] Read more.

Oxysophocarpine (OSC), a quinolizidine alkaloid, shows neuroprotective potential, though its mechanisms are unclear. The aim of the present study was to investigate the neuroprotective effects of OSC through the nuclear factor erythroid 2−related factor 2 (Nrf2)/ heme oxygenase−1 (HO–1) signaling pathway using the HT–22 cell line. Assessments of cell viability were conducted utilizing the 3−(4,5−dimethylthiazol−2−yl)−2,5−diphenyltetrazolium bromide (MTT) assay. Assessments of oxidative stress (OS) were conducted through the quantification of reactive oxygen species (ROS). The integrity of the mitochondrial membrane potential (MMP) was scrutinized using fluorescent probe technology. Apoptosis levels were quantified using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. The trafficking of Nrf2 within the cell nucleus was examined through immunofluorescence analysis. Furthermore, Western blotting (WB) was applied to evaluate the expression levels of proteins implicated in apoptosis and the Nrf2/HO–1 pathway. To further probe the influence of OSC on the overexpression of antioxidant enzymes, cells were subjected to transfection with HO–1 siRNA. The results showed that OSC inhibited glutamate-induced OS, as evidenced by reduced cell viability and ROS levels. Furthermore, the apoptotic condition induced by glutamate in HT–22 cells was significantly reduced following OSC treatment. More interestingly, the Nrf2/HO–1 signaling pathway was upregulated following OSC treatment. These results suggest that OSC can exert neuroprotective effects by regulating the Nrf2/HO–1 pathway to inhibit neuronal cell apoptosis, potentially aiding in the treatment of neurodegenerative diseases. Full article

(This article belongs to the Section Molecular Pharmacology)

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14 pages, 2606 KiB

Open AccessArticle

Alliin Induces Reconstitution of Testes Damaged by Estrogen Overstimulation by Regulating Apoptosis

by Dae-Seung Kim, Min-Jee Oh and Sang-Hwan Kim

Curr. Issues Mol. Biol. 2024, 46(11), 13021-13034; https://doi.org/10.3390/cimb46110776 - 16 Nov 2024

Abstract

We analyzed the effect of alliin on the recovery of mouse testicular function and structure following estradiol treatment as well as on apoptosis regulation. During the cultivation of testicular cells, high-concentration estradiol suppressed Casp-3; PCNA, mTOR, and PI3K signaling increased; and cell proliferation [...] Read more.

We analyzed the effect of alliin on the recovery of mouse testicular function and structure following estradiol treatment as well as on apoptosis regulation. During the cultivation of testicular cells, high-concentration estradiol suppressed Casp-3; PCNA, mTOR, and PI3K signaling increased; and cell proliferation in the testes was abnormally increased. Therefore, estradiol treatment increased the proportion of abnormal cells. The estradiol and 2.5 μM of alliin treatment increased Casp-3 levels and suppressed Bcl-2, PCNA, mTOR, and PI3K expression. Additionally, treatment with estradiol caused tissue loss. Furthermore, Ca²⁺ deposition decreased, TNF-r protein expression increased, and the levels of other protein markers of cell survival and death decreased. Tissue recovery and restoration of the testes occurred after alliin treatment; the gene expression of cell survival and death markers, except for TNF-r, increased with increasing Ca²⁺ deposition. Cell proliferation and tissue reorganization may correlate with an increased signal of intrinsic apoptosis owing to increased Ca²⁺ deposition. Therefore, treatment with alliin may regulate the apoptosis of cells with normal or abnormal signal transduction and help to revert testicular dysfunction. Full article

(This article belongs to the Special Issue Molecular Insights: Mechanisms Underlying the Biological Activities of Natural Products)

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