Current Issues in Molecular Biology最新文献

Antimicrobial resistance is a critical global health challenge, driven by the rapid emergence of multidrug-resistant bacterial pathogens and exacerbated by extensive antibiotic use, which imposes intense selective pressure and disrupts host-associated microbial communities. In this context, quorum sensing (QS), a conserved molecular communication system that coordinates population-level gene regulation, virulence expression, and biofilm development, has emerged as an attractive target for anti-virulence intervention. A growing body of evidence indicates that phytochemicals, such as curcumin, carvacrol, carnosol, eugenol, and chlorogenic acid, can modulate key QS pathways, including acyl-homoserine lactone-, autoinducing peptide-, and LuxS/AI-2-mediated signaling, thereby attenuating pathogenic behaviors at sub-inhibitory concentrations that do not directly impair bacterial viability. Despite this promise, the translational development of phytochemical-based QS inhibitors remains limited. Because QS also regulates cooperative and homeostatic functions in beneficial bacteria, QS-targeted interventions raise concerns about microbiome disruption and ecological imbalance. Furthermore, the literature is marked by substantial methodological heterogeneity, reliance on indirect phenotypic endpoints, limited molecular target validation, and insufficient assessment of toxicity, bioavailability, and pharmacokinetics. The predominance of simplified in vitro models further constrains extrapolation to complex host-associated and polymicrobial environments. This review critically examines the molecular mechanisms underlying phytochemical modulation of bacterial QS, synthesizes pathogen-focused experimental evidence, and evaluates key translational challenges arising from QS conservation, microbiome considerations, and methodological limitations. Addressing these barriers through mechanism-resolved experimentation, standardized evaluation frameworks, and microbiome-aware testing strategies will be essential for advancing phytochemical QS inhibitors toward clinically and industrially relevant anti-virulence applications.

Measles remains a significant global health threat due to its extreme transmissibility and the potential for severe, long-term complications. This review synthesizes the most up-to-date literature on the host response, immunological impact, current treatments, and prevention of the measles virus (MeV). The review details host immune evasion mechanisms, including the antagonism of interferon signaling, discusses genetic associations with vaccine failure, and explores adjunctive treatments like vitamin A and ribavirin. Despite the success of the two-dose MMR vaccine, recent resurgences in the United States, peaking at 2065 cases in 2025, underscore a critical decline in herd immunity driven by vaccine hesitancy and pandemic-related disruptions. However, with no FDA-approved antiviral, primary prevention via vaccination remains the only effective strategy. This paper emphasizes the necessity of strengthening public health outreach and standardizing international surveillance to mitigate the rising incidence of this preventable disease.

The variability in outcomes among individuals is caused by multiple factors, including genetic variations in drug transporter genes known as ABCs. This study investigates the clinical effect of single-nucleotide variants (SNVs) in the ABCC1/MRP1, ABCC2/MRP2, and ABCC4/MRP4 genes on the clinical response and relapse of pediatric patients with central nervous system tumors. In a cohort-based association study involving 111 cancer patients, genotyping of ABCC1/MRP1, ABCC2/MRP2, and ABCC4/MRP4 was conducted using real-time PCR with TaqMan probes. Treatment response was evaluated using the Response Assessment in Neuro-Oncology (RANO) criteria. Univariate and multivariate analyses were conducted using the Cox proportional hazards (adjusted) model. Multivariate analysis adjusted for sex and age showed a significant association between ABCC1 r.5540out G>C; rs12921623 in the gene and non-response to treatment in the codominant model [HR] 2.095, 95% CI 1.202-3.650, p = 0.009, and in the dominant model [HR] 2.025, 95% CI 1.199-3.421, p = 0.008, and an increased risk of relapse in the codominant model [HR] 9.09, 95% CI 1.04-78.85, p = 0.04, and in the dominant model [HR] 3.912, 95% CI 1.139-13.436, p = 0.03. Furthermore, a significant association was found between ABCC2 c. 3972 C>T; rs3740066 and relapse in the recessive model [HR] 3.5, 95% CI 1.02-12.17, p = 0.04. Our findings indicate that ABCC1 r.5540 G>C SNV and ABCC2 c. 3972 C>T SNV are significant predictors of non-response and relapse in this group of pediatric patients with central nervous system tumors.

Influenza A viruses remain a major public health threat due to their high mutation rates, antigenic variability, and the emergence of resistance to current antivirals, underscoring the need for novel therapeutic options. Natural compounds rich in polyphenols and flavonoids have attracted increasing attention as potential broad-spectrum antiviral agents. In this study, the activity of Rhus coriaria L. water extract against Influenza A virus in BEAS-2B human bronchial epithelial cells was investigated. Cell viability assay identified non-cytotoxic concentrations, up to 0.1 mg/mL, which were used in infection experiments. Viral replication was assessed at multiple levels by quantitative real-time PCR, western blotting, immunofluorescence and tissue culture infectious dose 50% (TCID₅₀). Treatment with R. coriaria extract resulted in a dose-dependent and statistically significant reduction of viral load. The extract decreased mRNA levels of Hemagglutin (HA), Neuraminidase (NA) and Matrix protein 2 (M2). Consistently, western blot analysis showed a decrease in major viral proteins HA, Nucleoprotein (NP), Matrix protein 1 (M1) and Polymerase Acidic protein (PA). Confocal images revealed a marked reduction in HA and PA signals, results that are statistically significant according to quantitative fluorescence evaluation. The convergence of results obtained through independent methodologies at both the transcriptional and protein levels highlight the robustness of the findings. These data provide the experimental evidence that Rhus coriaria interferes with influenza A virus replication in airway epithelial cells and support its further investigation as a promising phytochemical platform for the development of novel anti-influenza strategies.

Cancer therapy development increasingly focuses on multi-target approaches to inhibit key proteins involved in tumor growth and angiogenesis. This study explored the potential inhibitory interactions of 110 cannabinoid derivatives using molecular docking simulations against epidermal growth factor receptor (EGFR), vascular endothelial growth factor receptor-1 (VEGFR-1), and VEGFR-2. Blind docking with AutoDock Vina identified eight recurrent hits across all three targets, including polar THC glucuronides and more drug-like cannabinoid scaffolds. Among these, 2'-Hydroxy-Delta (9)-THC and Ajulemic Acid combined favorable multi-target binding with superior predicted pharmacokinetic properties compared with other cannabinoids and reference inhibitors (lapatinib, motesanib, and sorafenib). ADME predictions highlighted Ajulemic Acid as the most promising oral candidate, showing optimal molecular weight, high oral bioavailability, and good gastrointestinal absorption, while 2'-Hydroxy-Delta (9)-THC exhibited potential for central nervous system exposure due to predicted blood-brain barrier permeability. In contrast, glucuronidated THC metabolites and highly lipophilic cannabinol esters displayed strong docking scores but suboptimal drug-likeness, suggesting prodrug- or metabolite-like behavior rather than suitability as primary oral leads. Toxicity predictions classified all compounds as moderately toxic, with Ajulemic Acid showing a comparatively more favorable safety profile. These findings do not demonstrate biological inhibition and should be interpreted strictly as hypothesis-generating computational evidence, providing a rational framework for future in vivo and in vitro validations.

Immune response evasion is one of the hallmark features of cancer, which is not only the basis for cancer progression and metastasis but also affects the clinical management of cancer. Tumor immune evasion is mainly attributed to the dynamic and immunosuppressive tumor microenvironment (TME), which is regulated by a complex system including immunosuppressive cells and cytokines. Interleukin-18 (IL-18) is an important cytokine that plays a multifaceted role in immune system regulation, and its function is strictly regulated by the natural antagonist IL-18 binding protein (IL-18BP). IL-18 exhibits context-dependent immunoregulatory characteristics (acting as a "context resistor") during tumor occurrence and progression, which is closely related to cancer type, stage, and the signaling network of the tumor microenvironment. The multifaceted functions of IL-18 have been utilized in cancer treatment to reduce the phenomenon of immune escape of tumors. With the latest advancements in cancer research related to IL-18, it is necessary to integrate the latest research findings to deepen the understanding of the mechanism of tumor immune escape and promote the improvement of cancer treatment levels. This review will systematically elaborate on the action mode, core regulatory mechanism and key signaling pathways of IL-18 in tumor immune evasion, analyze the heterogeneity patterns associated with its context-dependent effects, comprehensively sort out the core obstacles in clinical translation, and at the same time, envision new precision treatment strategies based on IL-18 regulation.

The aim of this study was to investigate the regulatory roles of distinct signaling cascades within the death receptor pathway in host cell apoptosis induced by Eimeria tenella (E. tenella); to this end, primary chicken embryo cecal epithelial cell culture, gene silencing, enzyme-linked immunosorbent assay (ELISA), Hoechst-Annexin V/PI apoptosis staining, hematoxylin-eosin (HE) staining, and quantitative real-time polymerase chain reaction (qRT-PCR) were employed. At 4, 24, 72, and 120 h post-inoculation (hpi) with E. tenella sporozoites, the proportion of apoptosis in six treatment groups [Group C, Group T0 (E. tenella infection group), Group T1 (E. tenella + Fas SiRNA), Group T2 (E. tenella + TRAIL SiRNA), Group T3 (E. tenella + TNFR1 SiRNA), and Group T4 (E. tenella + NC SiRNA)] and the dynamic changes in Fas cell surface death receptor (Fas), tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), tumor necrosis factor receptor 1 (TNFR1), TNF receptor-associated death domain (TRADD), Fas-associated death domain (FADD), and death domain-associated protein (Daxx) expression and caspase-8 activity in the cells were determined. The results demonstrated that, from 4 to 120 hpi, the Fas and TNFR1 mRNA expression levels in Group T0's host cells were significantly higher than those in Group C (p < 0.05 or p < 0.01). At 72 and 120 hpi, TRAIL mRNA expression in Group T0's host cells was significantly or highly significantly elevated compared to that in Group C (p < 0.05 or p < 0.01). From 24 to 120 hpi, the expression levels of the FADD and Daxx genes, caspase-8 activity, and apoptotic rates in Group T1's host cells were significantly lower than those in Group T4 (p < 0.05). At 72 and 120 hpi, the FADD expression, caspase-8 activity, and apoptotic rates in Group T2's host cells were significantly reduced relative to Group T4 (p < 0.05). Additionally, at 4 hpi, TRADD gene expression in Group T3's host cells was significantly lower than that in Group T4 (p < 0.05), while the apoptotic rate was significantly higher (p < 0.05). However, from 24 to 120 hpi, the TRADD expression, caspase-8 activity, and apoptotic rates in Group T3's host cells were significantly lower than those in Group T4 (p < 0.05). The results indicated that, in the early stages of E. tenella development, TNFR1 overexpression promoted TRADD mRNA expression, thereby inhibiting the apoptosis of E. tenella host cells. In the middle and late developmental stages of E. tenella, the Fas-FADD, Fas-Daxx, TRAIL-FADD, and TNFR1-TRADD apoptotic pathways were all activated, collectively facilitating host cell apoptosis. The pro-apoptotic effects of these pathways were ranked in descending order, as follows: Fas signaling pathway > TNFR1 signaling pathway > TRAIL signaling pathway.

Rapid urbanization and significant lifestyle changes have become the risk drivers for the epidemiology of diseases. With urban transitions, substantial persistence of pollutants in the environment has been observed. Epidemiological studies indicate a strong relationship between air pollution and exacerbation of asthma and other allergic diseases due to particulate matter (PM). PMs in bioaerosols and aeroallergens induce the immune response, eliciting systemic inflammation. Continuous exposure to PM_2.5 along with gases like nitrogen oxide aggravate oxidative stress and inflammatory responses. Other pollutants elevate blood glucose, inducing poor sleep patterns which in turn induce low-grade chronic inflammation. This in turn acts as a trigger for adipocyte dysfunction and reduced energy expenditure. Taken together, air pollution, allergy, and obesity constitute a jigsaw with missing pieces. Transient Receptor Protein (TRP) channels have important roles in allergic rhinitis, systemic inflammation, adipogenesis, and obesity development, underscoring a potential role as a common mechanistic link. The goal of this review is to summarize and comprehend the intricate network connecting these "modern-day hyperendemic diseases" and the plausible role played by TRP in shaping their epidemiology. Bioactive compounds in dietary spices also modulate TRP channels. Thus, spices position themselves as potential regulators at the interface of environmental sensing, inflammation, and metabolism, indicating spice-based interventions may represent an adjunct strategy to alleviate the pollution-induced allergy and obesity risk.

Obesity, driven by chronic energy imbalance, has become a major global health burden and is strongly associated with metabolic disorders, including diabetes, hypertension, and cardiovascular disease. Conventional pharmacotherapies often exhibit limited long-term efficacy and are accompanied by undesirable side effects, highlighting the urgent need for safer and more sustainable strategies. Browning of White adipose tissue (WAT)-a process in which white adipocytes acquire brown fat-like thermogenic characteristics-has emerged as a promising approach to enhance energy expenditure and counteract obesity. Increasing evidence demonstrates that various diets and naturally occurring dietary bioactive compounds can effectively induce WAT browning through diverse molecular pathways. Among these, AMPK-, PPAR-, SIRT-, TRP channel-, β3-adrenergic-, and FGF21-related signaling cascades represent the major regulatory hubs linked to mitochondrial biogenesis, lipid metabolism, and thermogenesis. This review summarizes recent advances in diet-induced WAT browning, with particular emphasis on key dietary ingredients, their molecular targets, mechanistic pathways, and metabolic benefits. By integrating findings from in vitro studies, animal models, and emerging translational research, we provide updated insights that may guide the development of novel nutritional interventions, functional foods, and therapeutic strategies for obesity prevention and management.

Ankylosing spondylitis (AS) exhibits marked clinical heterogeneity that is poorly captured by conventional disease-centric analyses, hindering the development of personalized therapies. We propose a symptom-centered network pharmacology framework that directly links individual clinical symptoms to their underlying molecular mechanisms and therapeutic targets. AS- and symptom-associated genes were collected from GeneCards and prioritized using centrality analysis within protein-protein interaction networks. Symptom relevance was validated using patient-derived transcriptomic datasets. Network proximity between symptom modules and FDA-approved drug targets was assessed. A refined gene set, integrating TNF-associated neighbors and highly central nodes, was subjected to pathway enrichment analysis. Disease-centric analysis yielded a restricted 18-gene core enriched mainly in broad immune pathways. In contrast, the symptom-centered network identified 145 genes associated with specific symptoms such as inflammatory back pain and morning stiffness. Key genes, including PTEN, TLR4, JAK2, NRAS, and NR3C1, were significantly upregulated in AS patients. TNF showed local connectivity but limited global proximity, while IL17A- and JAK inhibitor-related targets were absent. A refined 24-gene module revealed enrichment in interleukin- and cytokine-mediated signaling pathways. Symptom-centered network analysis more effectively captures molecular heterogeneity in AS, providing a robust framework for symptom-specific target discovery and personalized therapeutic strategies.