Category: Nevin Manimala

Curr Issues Mol Biol. 2025 Jun 9;47(6):438. doi: 10.3390/cimb47060438.

ABSTRACT

Rhythms, regulated by core clock genes like the period (per) gene family, are crucial for maintaining physiological processes in animals. In teleost fish, including channel catfish (Ictalurus punctatus), these genes have evolved distinct functions. However, the evolutionary characteristics and functional roles of period genes, particularly in response to environmental cues such as feeding, remain unclear. This study aimed to investigate the evolutionary divergence and functional specialization of the period gene family in channel catfish, with a focus on feeding-induced rhythmicity. Four period genes, Ipper1b, Ipper2, Ipper2l, and Ipper3, were identified in channel catfish. Phylogenetic analysis revealed distinct evolutionary paths for these genes, with Ipper2l forming a separate clade from Ipper2. Tissue-specific expression analysis showed differential expression of period genes across tissues, with Ipper1b exhibiting the highest expression in the intestine and Ipper2 being predominantly expressed in the liver. Statistical analysis confirmed significant differences in the expression levels between tissues (p < 0.05), supporting the tissue-specific roles of these genes. Notably, under strict feeding schedules, we observed significant modulation of rhythmic expression in both the brain and liver, with a notable shift in the peak expression times and amplitude changes aligned with the feeding time. These results suggest that feeding serves as a critical Zeitgeber, entraining circadian rhythms in key tissues and potentially enhancing metabolic efficiency. These results demonstrated that feeding schedules play a key role in modulating circadian gene expression in channel catfish. This study provides insights into the evolutionary divergence and functional roles of the period gene family in channel catfish, showing how feeding schedules modulate circadian gene expression in the brain and liver. These findings have potential applications in optimizing feeding strategies for improving fish health and growth in aquaculture.

PMID:40699837 | DOI:10.3390/cimb47060438

Curr Issues Mol Biol. 2025 May 30;47(6):408. doi: 10.3390/cimb47060408.

ABSTRACT

Inferring time-varying gene regulatory networks from time-series single-cell RNA sequencing (scRNA-seq) data remains a challenging task. The existing methods have notable limitations as most are either designed for reconstructing time-varying networks from bulk microarray data or constrained to inferring stationary networks from scRNA-seq data, failing to capture the dynamic regulatory changes at the single-cell level. Furthermore, scRNA-seq data present unique challenges, including sparsity, dropout events, and the need to account for heterogeneity across individual cells. These challenges complicate the accurate capture of gene regulatory network dynamics over time. In this work, we propose a novel f-divergence-based dynamic gene regulatory network inference method (f-DyGRN), which applies f-divergence to quantify the temporal variations in gene expression across individual single cells. Our approach integrates a first-order Granger causality model with various regularization techniques and partial correlation analysis to reconstruct gene regulatory networks from scRNA-seq data. To infer dynamic regulatory networks at different stages, we employ a moving window strategy, which allows for the capture of dynamic changes in gene interactions over time. We applied this method to analyze both simulated and real scRNA-seq data from THP-1 human myeloid monocytic leukemia cells, comparing its performance with the existing approaches. Our results demonstrate that f-DyGRN, when equipped with a suitable f-divergence measure, outperforms most of the existing methods in reconstructing dynamic regulatory networks from time-series scRNA-seq data.

PMID:40699807 | DOI:10.3390/cimb47060408

Curr Issues Mol Biol. 2025 May 15;47(5):364. doi: 10.3390/cimb47050364.

ABSTRACT

Double-hydrolyzed collagen, a key structural protein, has gained increasing attention for its role in cancer progression and its potential therapeutic applications. This study aims to investigate the effects of double-hydrolyzed collagen (Type I and III peptides) on HCT116 colon carcinoma cells and CCD-18Co fibroblasts as a normal control. Cells were treated with 0.5 µg/mL, 1 µg/mL, and 1.5 µg/mL of collagen peptide solution. HCT116 and CCD-18Co cells were cultured under standard conditions and treated with 1 µg/mL collagen. Cell viability (MTT assay), migration (scratch assay), oxidative stress (TAS/TOS kits), TNF-α expression (qRT-PCR), and tumor marker levels (CA19-9, CEA, CA72-4, and CYFRA 21-1; CLIA) were evaluated. Cell viability, proliferation, migration, oxidative stress, and tumor marker levels were assessed. Statistical analyses were performed to determine significance. Double-hydrolyzed collagen treatment significantly increased CCD-18Co fibroblast proliferation (p = 0.0143), while HCT116 cancer cell numbers significantly decreased (p = 0.0045). Migration of HCT116 cells was markedly reduced (p < 0.0001), whereas no significant effect was observed in CCD-18Co fibroblasts (p = 0.559). Oxidative stress analysis showed decreased total oxidative status (TOS) and increased total antioxidant status (TAS) in HCT116 cells (p = 0.0075 and p = 0.0095, respectively), with no significant changes in normal fibroblasts. Among tumor markers, CA19-9 levels were significantly reduced in HCT116 cells (p = 0.013), while CEA, CA72-4, and CYFRA 21-1 remained unchanged. TNF-α gene expression analysis confirmed the absence of inflammatory or adverse effects in normal fibroblasts. These findings suggest that double-hydrolyzed collagen selectively inhibits colon cancer cell proliferation and migration, modulates oxidative stress, and reduces CA19-9 levels while promoting fibroblast growth. The differential effects between cancerous and normal cells highlight collagen’s potential as a complementary therapeutic approach for colorectal cancer. Further research is needed to elucidate the underlying mechanisms and assess its clinical applicability. Double-hydrolyzed collagen appears to be a safe and beneficial dietary component with promising biological effects and therapeutic potential.

PMID:40699763 | DOI:10.3390/cimb47050364

Curr Issues Mol Biol. 2025 Apr 28;47(5):311. doi: 10.3390/cimb47050311.

ABSTRACT

Psoriasis is a chronic inflammatory skin disease marked by abnormal keratinocyte proliferation and immune dysregulation. The vitamin D receptor (VDR) plays a crucial role in regulating skin cell growth and immune responses, but its expression in psoriatic skin and modulation by treatment remain unclear. This study aimed to analyze VDR mRNA expression in psoriatic skin tissue before and after etanercept therapy using RNAscope, an RNA in situ hybridization technique that, to the best of our knowledge, has not previously been applied in psoriasis research. Two bio-naïve adult patients with moderate to severe plaque psoriasis received etanercept (50 mg weekly) for 12 weeks. Skin biopsies from lesional and perilesional areas were collected at baseline and post-treatment. VDR expression was assessed in different epidermal layers and the dermis using a semi-quantitative scoring system. In one patient, a statistically significant decrease in VDR expression was observed in the perilesional dermis after treatment (p < 0.001), though this preliminary finding warrants careful interpretation given the very limited cohort size. Both patients exhibited a non-significant trend toward increased VDR expression in the lesional epidermis post-treatment. These preliminary findings suggest that etanercept may modulate VDR expression in psoriatic skin, but individual variability and the small sample size preclude definitive conclusions. The study primarily demonstrates the feasibility of using RNAscope for VDR analysis in patients with psoriasis, an approach that may be novel in this context, and underscores the need for larger investigations to confirm these preliminary findings and further clarify the role of VDR in disease pathogenesis and treatment response.

PMID:40699711 | DOI:10.3390/cimb47050311

Curr Issues Mol Biol. 2025 Apr 26;47(5):306. doi: 10.3390/cimb47050306.

ABSTRACT

The objectives of this study comprise the identification of key miRNAs and their target genes associated with severe tolerance in individuals exposed to aluminum and welding fumes, and the elucidation of the underlying regulatory mechanisms. In this study, the levels of seven miRNAs (hsa-miR-19a-3p, hsa-miR-130b-3p, hsa-miR-25-3p, hsa-miR-363-3p, hsa-miR-92a-3p, hsa-miR-24-3p, and hsa-miR-19b-3p) were analyzed using both hsa-miR-16-5p and RNU6 (U6 snRNA) as reference miRNAs to validate normalization reliability. The qRT-PCR method was used on blood serum samples from 16 workers who were exposed to aluminum, 16 workers who were exposed to welding fumes, and 16 healthy controls who were not exposed to aluminum or welding fumes. We determined heavy metal levels from serum samples of workers exposed to aluminum and welding fumes and control groups using the ICP-OES method. The expression levels of hsa-miR-19a-3p and hsa-miR-19b-3p in aluminum-exposed and control groups were found to be statistically significant (p < 0.05). When workers exposed to welding fumes were compared with the those in the control groups, the expression levels of hsa-miR-19a-3p, hsa-miR-130b-3p, hsa-miR-92a-3p, and hsa-miR-24-3p were observed to be statistically significant (p < 0.05). This study shows that the identification of miRNAs and target genes in different biological functions and pathways plays an important role in understanding the molecular mechanisms of responses to heavy metal toxicity. We share the view that the study will make a significant contribution to the literature in that seven candidate miRNAs can be used as possible biomarkers for exposure to aluminum and welding fumes in humans.

PMID:40699705 | DOI:10.3390/cimb47050306

Curr Issues Mol Biol. 2025 Apr 11;47(4):271. doi: 10.3390/cimb47040271.

ABSTRACT

BACKGROUND: This case-control study investigates whether miR-27a rs895819 A>G polymorphism is associated with an increased risk of recurrent pregnancy loss (RPL) in Caucasian Greek women.

METHODS: This study included 93 women with at least two unexplained miscarriages before the 24th week of gestation (RPL group) and 107 women with no pregnancy loss history (control group). The miR-27a rs895819 A>G polymorphism was detected using PCR amplification, followed by DraIII-HF restriction enzyme digestion.

RESULTS: The GG genotype was linked to a significantly higher risk of RPL (p-value = 0.00005), whereas the AA genotype was associated with a significantly lower risk (p-value = 0.00036). The AG genotype appeared more frequently in women with RPL (49.5% vs. 44.9% in controls), but the difference was not statistically significant (p-value = 0.5139).

CONCLUSIONS: To our knowledge, this is the first study demonstrating that the miR-27a A>G polymorphism was significantly associated with a higher risk of recurrent miscarriage in Caucasian women. These findings provide evidence that the GG genotype may serve as a potential genetic marker for identifying women at higher risk of recurrent miscarriage, offering valuable insights for genetic counseling and reproductive medicine.

PMID:40699670 | DOI:10.3390/cimb47040271

Curr Issues Mol Biol. 2025 Apr 9;47(4):266. doi: 10.3390/cimb47040266.

ABSTRACT

Current research discusses the putative importance of RNA modification in tumor diseases. These RNA modifications include predominantly pseudouridinylation, ortho-methylations on the ribose residues, as well as methylations on the organic bases. Such chemical modifications directly influence fundamental properties such as transcript stability, alternative splicing, and translation efficiency, all of which are basic requirements for (tumor) cell proliferation, cell metabolism, cell migration, apoptosis resistance, etc. In this comparative study, the two RNA-modifying factors, pseudouridine synthase 7 (PUS7, RNA pseudouridinylation) and WT1-associated protein (WTAP, m6A RNA methylation), were identified using data from human renal cell carcinoma (RCC) tumors. PUS7 and WTAP showed a statistically significant correlation with relevant proliferation and prognosis markers such as CXCR4, TP53, PTEN, and NRAS, as well as with the two tumor immune checkpoints HLA-G and LGALS9 and were directly associated with a statistically significant effect on overall survival. Furthermore, comparative analyses also identified further putative target mRNAs of importance for tumor biology of PUS7 and WTAP. In particular, components with direct relevance for mitosis, the cell cycle, and cell division, as well as the WNT pathway, were identified.

PMID:40699665 | DOI:10.3390/cimb47040266

Curr Issues Mol Biol. 2025 Apr 7;47(4):255. doi: 10.3390/cimb47040255.

ABSTRACT

Kidney transplantation is the preferred treatment for chronic kidney disease, significantly improving patient survival and quality of life. After the procedure, there is a gradual tendency to normalize most of the physiological and metabolic processes, but the need for immunosuppression may lead to new disorders related to the drugs’ side effects and changes in proportions of body composition. The aim of the study was to analyze the concentrations of adipocytokines such as leptin, adiponectin, visfatin, and resistin, and to assess the body composition in patients with stabilized kidney graft function treated with tacrolimus, mycophenolate mofetil, and glucocorticosteroids. A total of 47 participants were enrolled, including 25 kidney transplant recipients on uniform immunosuppressive therapy and 22 healthy controls. The concentrations of leptin, adiponectin, and IL-6 in kidney transplant recipients was significantly higher than in the control group (p = 0.014, p = 0.031, p = 0.000, respectively), while the other adipocytokines, such as visfatin and resistin, do not obtain statistically significant differences. The bioelectrical impedance analysis showed statistically significant differences for fat-free mass index (p = 0.027), visceral fat area (p = 0.023), waist circumference (p = 0.006), fat mass (p = 0.028), and fat mass index (p = 0.034), all of which had higher mean values in the study group. Preliminary findings suggest that kidney transplantation leads to significant alterations in adipocytokines levels, with potential implications for metabolic health.

PMID:40699654 | DOI:10.3390/cimb47040255

Curr Issues Mol Biol. 2025 Mar 28;47(4):236. doi: 10.3390/cimb47040236.

ABSTRACT

BACKGROUND: Our aim was to assess the expression profiles of the messenger RNA (mRNA) expression profiles of stem-cell genes (POU5F1, NANOG) and pancreatic progenitor genes (CK19, HES1, INS, PDX1) in peripheral-blood mononuclear cells (PBMCs) in selected neoplastic pancreatic diseases, such as cancer and neuroendocrine tumors, to identify neoplastic disease markers in the pancreas.

METHODS: In this study, 49 patients diagnosed with pancreatic neoplastic diseases (37 with cancer and 12 with neuroendocrine tumors) and 34 control patients, all of whom were hospitalized at a tertiary center, were enrolled. Venous blood samples were collected from the participants, and RNA was extracted from PBMCs. The mRNA expression levels of six stem-cell and pancreatic progenitor markers- POU5F1 (POU class 5 homeobox 1), NANOG, CK19 (keratin 19), HES1 (HES family bHLH transcription factor 1), INS (insulin), and PDX1 (pancreatic and duodenal homeobox 1)-were quantified via real-time quantitative PCR. The data were statistically analyzed to explore associations between gene-expression levels and various clinical, biochemical, and morphological parameters (including full blood count, Ca 19-9, weight, height, and BMI) via the Kruskal-Wallis test, Mann-Whitney U test, and Spearman rank correlation coefficient.

RESULTS: The results revealed that the expression of the gene associated with early stem cells, NANOG (median= 0.002, p = 0.03), as well as the genes encoding insulin INS (median = 0.004, p = 0.02) and CK19 (median 0.0003, p = 0.005), was significantly elevated in patients with pancreatic cancer. However, the gene-expression levels in patients with neuroendocrine tumors did not exhibit statistically significant differences compared to those observed in the control group. Additionally, no significant differences in gene expression were observed among patients at different stages of pancreatic cancer. Furthermore, CK19 overexpression was found to be positively correlated with inflammatory markers, specifically C-reactive protein (CRP) and WBC, in patients with pancreatic cancer.

CONCLUSIONS: An elevated mRNA expression of specific stem and pancreatic progenitor genes (NANOG, INS, CK19) in PBMCs may serve as a potential markers for pancreatic cancer, reflecting the disease’s interplay with systemic inflammation.

PMID:40699634 | DOI:10.3390/cimb47040236

Curr Issues Mol Biol. 2025 Mar 27;47(4):231. doi: 10.3390/cimb47040231.

ABSTRACT

Mesenchymal stromal cells (MSCs) influence tumor biology and immunology by releasing cytokines, chemokines and growth factors. Currently, cisplatin is an integral part of drug-based tumor therapy, for example, in head and neck squamous cell carcinoma (HNSCC). Cisplatin treatment induces apoptosis as a primary mechanism of action; however, additional immunomodulatory effects of cisplatin are gaining interest. The aim of this study is to evaluate the possible immunomodulatory effects of cisplatin in human MSCs (hMSCs). The MSCs, obtained from human bone marrow, were characterized by analyzing plastic adherence, typical surface features, and ability to differentiate. Toxicity analysis of cisplatin’s effects on primary MSCs, including the determination of a subtoxic concentration, was performed using the MTT assay. Enzyme-linked immunosorbent assays (ELISA) and a quantitative real-time polymerase chain reaction (qRT-PCR) were used to identify potentially immunomodulatory factors. Additionally, a scratch assay was performed to evaluate cell migration. First, subtoxic cisplatin concentrations were determined. A significantly reduced protein expression of indoleamine 2,3-dioxygenase 1 (IDO1) in MSCs under the influence of subtoxic cisplatin concentrations was demonstrated. Similarly, IL-6 protein expression was qualitatively reduced at subtoxic concentrations, although without statistical significance. At the mRNA level, qRT-PCR showed a non-significant, cisplatin concentration-dependent reduction in the expression of both IL-6 and IDO1. The scratch assay showed no statistically significant influence on migration after cisplatin treatment. In MSCs, there is tendency to a decrease in IL-6 and IDO1 at both protein and mRNA level after cisplatin exposure. These effects are congruent with each other and dose-dependent. This indicates that cisplatin not only acts via the known cytotoxic effect, but may induce a reduction in tumor-supporting proteins, like IL-6 and IDO1, by MSCs in the tumor microenvironment at subtoxic concentrations. Traditional cytostatic compounds, which can favorably modulate the immune system in the tumor microenvironment, may open new avenues to explore treatment strategies specifically targeting immunomodulation. Overall, the results indicate beneficial immunomodulation by cisplatin.

PMID:40699630 | DOI:10.3390/cimb47040231