Current Issues in Molecular Biology最新文献

The Molecular Microbiology section of Current Issues in Molecular Biology publishes original research and review articles on microbes, including bacteria, archaea, eukaryotic microorganisms, and viruses [...].

In our study, we aimed to investigate the relationship between miRNA-21, miRNA-155, miRNA-34a, IL-6, TGF-β, and TNF-α expression levels and serum trace element levels in the development and progression of bladder cancer. RT-PCR was used to establish miRNA-21, miRNA-155, and miRNA-34a expression levels while serum IL-6, TGF-β, and TNF-α levels were determined using the ELISA and measured with an atomic absorption spectrophotometer. In the patient group, miRNA-21 and miRNA-155 expression levels were significantly higher compared with the healthy control group (p < 0.001). Furthermore, in the patient group, miRNA-34a expression was significantly lower compared with the control group (p < 0.001). IL-6, TNF-α, TGF-β, copper levels, and the copper to zinc ratio were significantly higher in the patient group (p < 0.001). Serum iron and zinc levels in the patient group were significantly lower compared with the control group (p < 0.001). There was a significant positive correlation between miRNA-155 and IL-6 and TNF-α (r = 0.279, p = 0.015*; r = 0.325**, p = 0.004). A significant positive correlation was detected between miRNA-34a and IL-6 and TGF-β (r = 0.294*, p = 0.010; r = 0.447**, p < 0.001). By evaluating these important biomarkers together, it might be possible to implement clinical applications for bladder cancer treatment and develop individual therapeutic strategies.

Background: Parvovirus B19 (B19V; Erythroparvovirus primate 1) is now the most commonly detected virus in human endomyocardial biopsies from patients with myocarditis or dilated cardiomyopathy; however, its true causal role remains uncertain. By contrast, Protoparvovirus carnivoran 1, also known as canine parvovirus type 2 (CPV-2), is an apparent cause of myocarditis in neonatal puppies, where it replicates in cardiomyocytes, induces extensive cell death, and often leaves fibrotic scars in survivors.

Conclusions: This review compares B19V and CPV-2 from basic biology to clinical expression. Divergent tropism and replication kinetics produce distinct injury patterns: predominantly endothelial and microvascular dysfunction with immune-mediated damage in adult human B19V infection versus direct, age-restricted cardiomyocyte lysis in neonatal CPV-2 infection, often followed by fibrosis. Because parvoviral DNA can persist in cardiac tissue, detection alone does not prove causality. We advocate an "evidence bundle" integrating viral load by quantitative polymerase chain reaction (qPCR), detection of viral transcripts and/or proteins when feasible, spatial co-localization with histological injury, and concordant clinical markers (cardiac troponins and advanced imaging, including cardiac magnetic resonance imaging [CMR]) to support etiologic attribution and guide management in human and veterinary cardiology.

Background: Functional dermatological bases can contribute more than just delivery-they may actively modulate cutaneous homeostasis. Cleoderm™ is a dermofunctional base containing a patented Cleome gynandra extract, palmitoyl tripeptide-8, bisabolol, hyaluronic acid, and functional oils, rationally designed to provide anti-inflammatory, antioxidant, and barrier-supportive properties.

Objective: To determine whether Cleoderm™ exhibits intrinsic immunomodulatory and matrix-protective effects in a physiologically relevant skin co-culture and to clarify the biomarkers most impacted, with translational relevance to acne and rosacea.

Methods: Human keratinocytes and fibroblasts were maintained in a transwell co-culture. Non-cytotoxic concentrations of Cleoderm™ (1.0% and 10.0%, v/v) were tested with or without LPS stimulation (1 μg/mL). Viability was assessed by MTT and Trypan Blue. Cytokines (IL-6, TNF-α, IL-10, TGF-β) and MMPs (MMP-1, -3, -13) were quantified by ELISA and RT-qPCR. LL-37, IGFBP-3, and TGF-β protein levels were evaluated by Western blot.

Results: Cleoderm™ showed no cytotoxicity up to 10% (v/v). It significantly reduced pro-inflammatory mediators (IL-6, TNF-α) and matrix-degrading enzymes (MMP-1, MMP-3, MMP-13) while increasing anti-inflammatory/reparative cytokines (IL-10, TGF-β). A dual, biomarker-level modulation was observed: (i) LL-37 was reduced, with a particularly pronounced decrease in secreted levels; and (ii) IGFBP-3 was markedly upregulated, indicating potential attenuation of the IGF-1 axis relevant to sebaceous lipogenesis. Collectively, these effects indicate immunoregulatory and matrix-protective activity consistent with improved cutaneous homeostasis.

Conclusion: In a dermo-epidermally relevant in vitro model, Cleoderm™ functions as an active dermofunctional base, not merely a vehicle simultaneously tempering inflammatory signaling, preserving extracellular matrix integrity, and modulating mechanistic nodes (LL-37 and IGFBP-3) linked to rosacea and acne. These findings is consistent with the use of Cleoderm™ as a biologically supportive base for personalized compounding and justify controlled clinical evaluation.

Accurate post-mortem diagnosis of sepsis remains a critical challenge in forensic pathology, as conventional morphological findings often lack specificity. Circulating microRNAs (miRNAs) have been proposed as stable molecular biomarkers, yet their diagnostic value in cadaveric samples is still unclear. This exploratory study investigated the expression of three candidate miRNAs (miR-122-5p, miR-125b-5p, and miR-27a-3p) in post-mortem peripheral whole blood to assess their association with sepsis-related death versus non-infective controls. Out of 58 cases, 45 met quality-control criteria (26 sepsis-related deaths and 19 controls). miRNA expression was quantified by qRT-PCR, normalized to miR-320, and analyzed using ΔCt values. Group differences were evaluated using linear regression models with adjustment for age, sex, and post-mortem interval, with Benjamini-Hochberg correction for multiple testing. In adjusted models, miR-125b-5p and miR-27a-3p showed evidence of association with sepsis status, whereas miR-122-5p did not. These results support the feasibility of miRNA quantification in post-mortem samples and motivate validation in larger, independent cohorts and within multimodal post-mortem diagnostic frameworks.

Kynurenic acid (KYNA), a small molecule derived from the tryptophan-kynurenine pathway, can readily diffuse across biological membranes and act as an endogenous ligand for receptors such as the aryl hydrocarbon receptor (Ahr). While KYNA dysregulation is implicated in neurodegenerative disorders, the role of the KYNA-Ahr-IL-6 axis in MSC proliferation and differentiation remains poorly defined. We investigated the impact of KYNA on murine bone marrow-derived MSCs (BM-MSCs) at various concentrations (10-200 μM) and time points (8-48 h). The BM-MSC phenotype was assessed via flow cytometry; proliferation, via cell counting; and the gene expression of Ahr, Cyp1a1, Cyp1b1, and Il-6, via quantitative real-time PCR. Multipotency was evaluated through adipogenic, osteogenic, and chondrogenic differentiation assays with histochemical confirmation. KYNA significantly upregulated Ahr mRNA expression. Among the tested concentrations, 100 μM KYNA induced the highest Ahr expression (~19.1 ± 1.5-fold greater than that of the untreated controls, p < 0.005). Notably, 10 and 50 μM KYNA caused moderate induction, whereas compared with 100 μM KYNA, 200 μM did not further increase expression. In addition, KYN treatment increased Cyp1a1, Cyp1b1, and Il-6 expression, with increases of ~64.6 ± 4.5-fold, ~43.6 ± 2.3-fold, and ~41.6 ± 1.2-fold, respectively. Compared with no treatment, 100 µM KYNA enhanced BM-MSC proliferation by 1.210 ± 0.02, 1.189 ± 0.03, and 1.242 ± 0.02-fold across passages P3, P4, and P5, respectively (p < 0.05), without altering Sca-1, CD90, or CD45 expression or impairing trilineage differentiation potential. KYNA may activate the AHR-IL-6 signaling axis to promote BM-MSC expansion. This controlled proliferative effect, without loss of phenotypic or functional integrity, highlights the pharmacological potential of KYNA as a small-molecule modulator for stem cell-based therapies.

This study investigated the effects and mechanisms of broccoli extract containing more than 99.0% β-NMN (BRC) on UVB-induced skin damage, including moisture loss, oxidative stress, inflammation, wrinkle formation, and melanin production, using in vitro and in vivo models. BRC treatment significantly alleviated UVB-induced skin dehydration, oxidative stress, and inflammatory responses, as well as inhibited wrinkle formation and melanin synthesis. Mechanistically, BRC enhanced skin hydration and barrier function by upregulating hyaluronic acid synthases and genes related to sphingolipid metabolism, while simultaneously suppressing NF-κB signaling and COX-2 expression, thereby re-ducing inflammation. Moreover, BRC promoted collagen synthesis by activating the TGF-βR1/Smad3/Collagen pathway and prevented extracellular matrix degradation by inhibiting JNK/c-Fos/c-Jun/MMPs signaling. In addition, BRC modulated the cAMP/PKA/CREB/MITF/TRPs pathway, leading to reduced melanin production. These findings suggest that BRC supplementation may effectively protect against UVB-induced skin damage, supporting its potential application as a functional ingredient for skin health.

Atrial fibrillation (AF) is the most common sustained arrhythmia, and its initiation and progression involve multiple mechanisms, including electrical remodeling, structural remodeling, inflammatory responses, and oxidative stress. In recent years, the ubiquitin-proteasome system (UPS), a central pathway for maintaining intracellular protein homeostasis, has attracted increasing attention in the pathogenesis of AF. By regulating the degradation and expression of ion channel proteins, Ca²⁺-handling molecules, and pro-fibrotic signaling factors, the UPS plays a pivotal role in key pathological processes such as electrical and structural remodeling. Several E3 ubiquitin ligases (e.g., NEDD4-1/2, MuRF1, WWP1/2, TRAF6), deubiquitinating enzymes (e.g., JOSD2), and immunoproteasome subunits (e.g., β5i) have been shown to exert critical regulatory effects on atrial electrophysiological disturbances, interstitial remodeling, and inflammation. This review provides a comprehensive summary of the regulatory mechanisms of the UPS in AF-associated pathological processes, outlines potential therapeutic targets, and highlights current intervention strategies, including proteasome inhibitors, selective E3 ligase modulators, and natural compounds. Moreover, we discuss the latest advances and future perspectives regarding the application of UPS-based interventions in AF, aiming to provide theoretical foundations and research insights for the mechanistic exploration and innovative therapeutic development of AF.

Immunization is the most effective way to prevent transmission of the hepatitis B virus. However, about one-quarter of hepatitis B vaccinees (HepB vaccinees) aged around 18 years have lost their immune memory. What is responsible for the loss? Five subjects who became asymptomatic HBsAg carriers after anti-HBs seroconversion and ten controls who were negative for both HBsAg and anti-HBs were recruited from individuals born in 1987 and vaccinated at birth. scRNA-seq was performed on peripheral blood mononuclear cells, including library preparation, sequencing, quality control and filtering, normalization, dimensionality reduction, clustering, cell type annotation, differential expression analysis and trajectory analysis. Twelve cell types and nine subpopulations of T cells were identified. No significant differences in the proportions of cell types and subpopulations were found between cases and controls. The expression levels of immune memory-related genes, IL7R in total T cells and BACH2 in naive CD4+ T cells and naive CD8+ T cells, were significantly downregulated in the cases (p = 2.2 × 10^-308, 3.31 × 10^-27 and 9.41 × 10^-100, respectively). IL7R is expressed throughout cellular development, while BACH2 is expressed only in the early stage of cellular development. Downregulation of the IL7R and BACH2 in T cells is associated with immune memory loss, identifying them as candidate genes for future functional studies to explore their potential role in the loss of immune memory. This could inform adjuvant design if a causal mechanism is firmly established.

The field of neurodegenerative diseases represents one of the most challenging and fascinating areas of modern cellular and molecular biology [...].