Current Issues in Molecular Biology最新文献

{"title":"Alpha-Lipoic Acid in Diabetic Peripheral Neuropathy: Addressing the Challenges and Complexities Surrounding a 70-Year-Old Compound.","authors":"Iliya Mangarov, Yulian Voynikov, Valentina Petkova, Simeon Iliev, Ivanka Kostadinova, Lyubomir Marinov, Irina Nikolova","doi":"10.3390/cimb47060402","DOIUrl":"https://doi.org/10.3390/cimb47060402","url":null,"abstract":"<p><p>Alpha-lipoic acid (ALA, also known as thioctic acid) was discovered nearly 90 years ago and began to be used in clinical practice in the late 1950s. Numerous nonclinical and clinical studies have investigated ALA for treating diabetic peripheral neuropathy (DPN) and various other diseases. The rising global prevalence of DPN necessitates timely treatment; however, there is currently no effective cure. Current guideline-recommended therapies for DPN provide symptom relief rather than modifying the disease. Among the pathogenesis-oriented therapies, ALA holds a unique position as a universal antioxidant, essential for every cell in the body. This review highlights the ongoing issues and challenges in using ALA to treat DPN. While confronting a complex disease with poorly understood pathophysiology, we also have an endogenous substance with pleiotropic effects on all cells in the human body. It becomes clear that this is a highly multifactorial process that will likely never be precisely defined. This does not diminish the significance of ALA in treating DPN but underscores the need for a deeper understanding of when to start therapy, dosage, duration, and monitoring. In this comprehensive review, we evaluate the achievements of the past 70 years and highlight gaps in ALA's role in treating DPN.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"47 6","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144689333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioinformatic RNA-Seq Functional Profiling of the Tumor Suppressor Gene OPCML in Ovarian Cancers: The Multifunctional, Pleiotropic Impacts of Having Three Ig Domains.","authors":"Adam G Marsh, Franziska Görtler, Sassan Hafizi, Hani Gabra","doi":"10.3390/cimb47060405","DOIUrl":"https://doi.org/10.3390/cimb47060405","url":null,"abstract":"<p><p>The IgLON family of tumor suppressor genes (TSG) impact a variety of cellular processes involved in cancer and non-cancer biology. OPCML is a member of this family and its inactivation is an important control point in oncogenesis and tumor growth. Here, we analyze RNA-Seq expression ratios in ovarian cancers from The Cancer Genome Atlas (TCGA) (189 subjects at Stage III) to identify genes that exhibit a cooperative survival impact (via Kaplan-Meier survival curves) with OPCML expression. Using enrichment analyses, we reconstruct functional pathway impacts revealing interactions of OPCML, and then validate these in independent cohorts of ovarian cancer. These results emphasize the role of OPCML's regulation of receptor tyrosine kinase (RTK) signaling pathways (PI3K/AKT and MEK/ERK) while identifying three new potential RTK transcriptomic linkages to KIT, TEK, and ROS1 in ovarian cancer. We show that other known extracellular signaling receptor ligands are also transcriptionally linked to OPCML. Several key genes were validated in GEO datasets, including KIT and TEK. Considering the range of OPCML impacts evident in our analyses on both external membrane interactions and cytosolic signal transduction, we expand the understanding of OPCML's broad cellular influences, demonstrating a multi-functional, pleiotropic, tumor suppressor, in keeping with prior published studies of OPCML function.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"47 6","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144689342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transgenerational Memory of Phenotypic Traits in Plants: Epigenetic Regulation of Growth, Hormonal Balance, and Stress Adaptation.","authors":"Erna Karalija, Saida Ibragić, Sabina Dahija, Dunja Šamec","doi":"10.3390/cimb47060404","DOIUrl":"https://doi.org/10.3390/cimb47060404","url":null,"abstract":"<p><p>Plants exhibit remarkable adaptability to environmental stresses, with epigenetic modifications playing a key role in stress memory and adaptation. This review explores how epigenetic mechanisms influence hormonal regulation in plants, shaping growth, development, and stress responses. Specifically, we focus on the roles of DNA methylation, histone modifications, and small RNAs in modulating auxin, abscisic acid (ABA), gibberellin (GA), and jasmonic acid (JA) pathways. These pathways influence the plant's ability to cope with abiotic and biotic stresses and can be inherited by progeny, enhancing stress resilience across generations. By understanding the epigenetic regulation of these hormones, we aim to provide insights into how epigenetic priming can be harnessed in crop improvement to address the challenges posed by climate change.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"47 6","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144689404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synergistic Antitumor Effects of Ivermectin and Metformin in Canine Breast Cancer via PI3K/AKT/mTOR Pathway Inhibition.","authors":"Huili Feng, Lixin He, Talha Umar, Xiao Wang, Wenxuan Li, Bohan Zhang, Xinying Zhu, Ganzhen Deng, Changwei Qiu","doi":"10.3390/cimb47060403","DOIUrl":"https://doi.org/10.3390/cimb47060403","url":null,"abstract":"<p><p>Ivermectin (IVM) is a macrolide antiparasitic drug, and Metformin (MET) is a biguanide oral hypoglycemic drug. Studies have shown that both of them have obvious anti-tumor effects, but there have been no reports on the combined treatment of Canine breast tumors. This report aimed to investigate the effectiveness and the possible mechanism of drug combination on Canine breast cancers. Mouse breast tumor cells (4T1) and canine breast tumor cells (CMT-1211) were, respectively, treated with IVM, MET, and their combination, and then cell viability was assessed. After that, transcriptomic analysis was performed to study the action pathway of the drug combination with regard to its anti-tumor effects. Reactive oxygen species (ROS) levels were detected by flow cytometry, and autophagosome formation was observed by transmission electron microscopy (TEM). Immunofluorescence detected the cytoplasmic translocation of LC3B and P62 into the nucleus. Western blot detected the protein expressions of LC3B, P62, Beclin1, Bcl-2, p-PI3K, p-AKT, and p-mTOR. Our transcriptomic analysis showed that the combination of IVM and MET regulated the expression of autophagy-related genes and pathways, including the PI3K/AKT/mTOR signaling pathway. Our in vitro experiments showed that the combination of two drugs had a considerably significant effect on cytotoxicity, ROS levels, and the formation of autophagosomes compared to each drug alone. Meanwhile, the in vivo experiments showed that IVM combined with MET had an obvious inhibitory effect on tumor growth in canine breast tumor xenografts. This study concluded that IVM with MET activated autophagy, which killed breast cancer cells by inhibiting the activation of the PI3K/AKT/mTOR pathway and promoting the excessive accumulation of ROS. It offers a theoretical foundation for the synergistic effects of MET and IVM to suppress breast cancer cell activity.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"47 6","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144689395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of Mucins in Cancer and Cancer Progression: A Comprehensive Review.","authors":"Clare Chen, Ameena Patel, Lusine Demirkhanyan, Christopher S Gondi","doi":"10.3390/cimb47060406","DOIUrl":"https://doi.org/10.3390/cimb47060406","url":null,"abstract":"<p><p>Mucin, a heavily glycosylated glycoprotein, serves an important function in forming protective and immune defense barriers against the exterior environment on epithelial surfaces. While secreted-type mucins are involved in mucous production, transmembrane mucins, which contain O-glycosylated tandem repeats, play a pivotal role in cellular signaling, especially in immune modulation and mediating inflammatory response. However, dysregulation in mucin expressions, such as MUC1, MUC2, MUC4, MUC5AC, and MUC16, have been observed in many cancer cells. More specifically, alterations in the expression and glycosylation of MUC1 have been associated with the upregulation of pathways involving the cell proliferation, angiogenesis, migration, and invasion of cancer cells. With mucin's extensive involvement in cancer biology, several mucin biomarkers, such as CA125, CA19-9, and CEA, have been utilized as diagnostic and prognostic monitoring biomarkers in ovarian, pancreatic, and colon cancer. Vaccines and antibody therapy against abnormal mucin glycosylation have also been investigated for potential therapy for mucin-related cancers that are resistant to traditional chemotherapy agents. Despite the lack of specificity in mucin biomarkers and challenges in efficient drug delivery systems, the current advancement in mucin-targeted immunotherapy highlighted the pivotal potential in developing therapeutic targets to improve cancer prognosis.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"47 6","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144689403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacological Evaluation of <i>Angelica keiskei</i> Extract: Molecular Interaction Analysis in Hepatocellular Carcinoma.","authors":"Alka Ashok Singh, Minseok Song, Gun-Do Kim","doi":"10.3390/cimb47060401","DOIUrl":"https://doi.org/10.3390/cimb47060401","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC), the most prevalent primary liver cancer, is the most significant cause of cancer-related death globally, with limited treatment options, including surgical resection, liver transplantation, ablation, chemoembolization, immunotherapy, and radiation. <i>Angelica keiskei</i>, a plant that is rich in chalcones and flavonoids, has demonstrated interesting anticancer properties. This study assesses the pharmacological effects of <i>Angelica keiskei</i> extract on HepG2 cells in order to investigate its efficacy as a therapeutic intervention for HCC. Using in vitro cell culture models, HepG2 cells were treated with different doses of the extract, and its cytotoxic and apoptotic effects were studied. GC-MS analysis revealed the presence of several bioactive compounds, including DDMP, which are likely involved in the observed effects. The MTT assay revealed a considerable, dose-dependent reduction in cell viability, with higher dosages causing notable morphological alterations. An antibody apoptotic array indicated significant changes in apoptotic proteins, specifically IGFBP1, BAD, and Bid. Cluster heatmaps, volcano plots, STRING analysis, Voom-mean variance trends, Glimma plots, and PCA were used to obtain an understanding of the molecular interactions involved. These results suggest that <i>Angelica keiskei</i> extract can cause apoptosis in HepG2 cells, with DDMP appearing as a potentially significant contributor. However, more experimental validation is required to determine the precise molecular mechanisms driving these favorable effects and their clinical implications in HCC.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"47 6","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144689314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular Effects of Cornelian Cherry Fruit (<i>Cornus mas</i> L.) Extract on Sleep Deprivation-Induced Oxidative Stress, Cytokine Dysregulation, and Behavioural Changes in Wistar Rats.","authors":"Vlad Sever Neculicioiu, Ioana Colosi, Alexandra Sevastre-Berghian, Dan Alexandru Toc, Horațiu Alexandru Colosi, Luminita David, Mara Muntean, Remus Moldovan, Ana-Maria Vlase, Vlad Alexandru Toma, Carmen Costache, Şoimiţa Mihaela Suciu, Simona Clichici","doi":"10.3390/cimb47060399","DOIUrl":"https://doi.org/10.3390/cimb47060399","url":null,"abstract":"<p><p>Sleep deprivation (SD) induces significant neurobiological changes, including oxidative stress, neuroinflammation, and behavioural impairments. This study was designed as a proof of concept to assess the potential for modulating the effects of SD through a short-term seven-day administration of <i>Cornus mas</i> (<i>C. mas</i>) in a rapid eye movement (REM) SD rodent paradigm. Adult male Wistar rats were randomised in four groups (n = 7): control, <i>C. mas</i> (CM), sleep deprivation (SD), and sleep deprivation with <i>C. mas</i> (SD + CM). Behaviourally, SD induced hyperactivity and hyperlocomotion. SD determined histological alterations in the prefrontal cortex and corpus callosum myelin coupled with ultrastructural mitochondrial and cellular abnormalities in the prefrontal cortex, hippocampus, and pineal gland. Despite evidence of systemic oxidative stress coupled with decreased serum GABA and BDNF following SD, no significant changes were observed in redox markers or inflammatory cytokine levels (TNF-α, IL-1β) within the prefrontal cortex or hippocampus. <i>C. mas</i> extract has shown an overall modest modulatory action, mainly evidenced on behavioural, histological, and ultrastructural parameters. Taken together, these findings highlight behavioural changes and region-specific molecular and structural abnormalities following prolonged REM SD in rats.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"47 6","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144689376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Niacin and Stroke: The Role of Supplementation and Emerging Concepts in Clinical Practice, a Narrative Review.","authors":"Alan D Kaye, Grant D Coffman, Sydney A Mashaw, Austin S Thomassen, Kalob M Broocks, Ahmed I Anwar, Shahab Ahmadzadeh, Sahar Shekoohi","doi":"10.3390/cimb47060400","DOIUrl":"https://doi.org/10.3390/cimb47060400","url":null,"abstract":"<p><p>Niacin therapy has been a mainstay in traditional secondary prevention of stroke. Supplemental use of niacin has been used to improve lipid panel markers, including lowering low-density lipoproteins and triglycerides, and raising high-density lipoproteins, which have been associated with lower risk for stroke. This supplementation has been supported by earlier studies regarding niacin and its role in reducing cardiovascular risk. However, recent studies have called into question the efficacy of niacin therapy and some studies even show negative effects that are associated with taking supplemental niacin. In the present investigation, review of niacin-mediated benefits to cardiovascular disease and newer research suggesting that niacin may be ineffective with the potential of adverse side effects are summarized. This review further highlights the need for more population-level studies regarding the effects of supplemental niacin use to provide a scientific basis for its therapeutic role in cardiovascular disease, including improvement in lipid panel markers and stroke prevention.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"47 6","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144689383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genome-Wide Characterization of the Heat Shock Transcription Factor Gene Family in <i>Begonia semperflorens</i> Reveals Promising Candidates for Heat Tolerance.","authors":"Zhirou Liu, Nan Lin, Qirui Wang, Enkai Xu, Kaiming Zhang","doi":"10.3390/cimb47060398","DOIUrl":"https://doi.org/10.3390/cimb47060398","url":null,"abstract":"<p><p><i>Begonia semperflorens</i> (<i>B. semperflorens</i>) is a popular ornamental plant widely used in landscapes such as plazas and flower beds, and it is also commonly grown as a potted plant indoors. It is known for its adaptability to high temperatures, drought, and shade. Under heat-tolerant conditions, heat shock transcription factors (HSFs) are key transcriptional regulatory proteins that play crucial roles in cellular processes. Despite extensive studies on the <i>HSF</i> family in various species, there has been no specific analysis targeting <i>B. semperflorens</i>. In this study, we identified 37 members of the <i>BsHSF</i> gene family in <i>B. semperflorens</i> based on its genome scaffold, which are unevenly distributed across the genome. Phylogenetic analysis reveals that these 37 members can be divided into three subfamilies. Analysis of their physicochemical properties shows significant diversity among these proteins. Except for the BsHSFB7 protein located in the cytoplasm, all other BsHSF proteins were found to be nuclear-localized. A comparison of the amino acid sequences indicates that all BsHSF proteins contain a conserved DNA-binding domain structure. Analysis of the promoter cis-acting elements also suggests that <i>BsHSFs</i> may be associated with heat stress and plant secondary metabolism. We further investigated the duplication events of <i>BsHSF</i> genes and their collinearity with genes from other Begonia species. Finally, through real-time quantitative PCR, we examined the expression patterns of the 37 <i>BsHSFs</i> in different plant tissues (roots, stems, leaves, and flowers) and their expression levels under heat stress treatment. The results show that, except for <i>BsHSF29</i>, all <i>BsHSFs</i> were expressed in various tissues, with varying expression levels across tissues. Except for <i>BsHSF33</i> and <i>BsHSF34</i>, the expression levels of almost all <i>BsHSF</i> genes increased in response to heat treatment. In summary, these findings provide a better understanding of the role and regulatory mechanisms of HSFs in the heat stress response of <i>B. semperflorens</i> and lay the foundation for further exploration of the biological functions of <i>BsHSFs</i> in the stress responses of <i>B. semperflorens</i>.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"47 6","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144689294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential Expression of lncRNAs in Ovarian Tissue of Meigu Goats During the Sexually Immature and Mature Periods.","authors":"Juntao Li, Yanan Xue, Tao Zhong, Linjie Wang, Li Li, Hongping Zhang, Siyuan Zhan","doi":"10.3390/cimb47060395","DOIUrl":"https://doi.org/10.3390/cimb47060395","url":null,"abstract":"<p><p>The ovary is the primary reproductive organ in goats, and its development significantly influences the sexual maturity and reproductive capacity of individuals. Long non-coding RNAs (lncRNAs) are integral to a wide array of biological processes. However, the regulatory function of lncRNAs in the development of ovarian tissue during sexual maturity in goats remains largely unexplored. In this study, we conducted RNA sequencing on ovarian tissue samples from Meigu goats at sexually immature (3 months, n = 3) and sexually mature periods (6 months, n = 3). We identified a total of 966 lncRNAs across six libraries, with 95 lncRNAs exhibiting differential expression. Additionally, we identified the target genes of these DElncRNAs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses indicated that these target genes were associated with various biological processes and pathways pertinent to ovarian development, including reproduction, reproductive process, JAK-STAT signaling pathway, progesterone-mediated oocyte maturation, Wnt signaling pathway, and cytokine-cytokine receptor interaction. Furthermore, lncRNA-mRNA interaction network analysis suggested that MSTRG.15120.9 and MSTRG.15110.2 play crucial regulatory roles in ovarian development. This study provides a valuable resource for elucidating the molecular regulatory mechanisms of lncRNAs in ovarian tissue during the sexual maturity period in goats.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"47 6","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144689353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}