Current Issues in Molecular Biology最新文献

Phosphoinositide 3-kinases (PI3Ks) are a class of key regulatory factors in eukaryotes that can inhibit viral replication by influencing autophagy. Currently, cyprinid herpesvirus 3 (CyHV-3) poses a serious threat to common carp culture. However, PI3K has not yet been identified in common carp. In this study, full-length PI3KC3 from common carp (CcPI3KC3), consisting of an open reading frame (ORF) of 2664 bp encoding a polypeptide of 887 amino acids, with a predicted molecular mass of 101.19 kDa and a theoretical isoelectric point (pI) of 5.97, was cloned. The amino acid and nucleotide sequences of CcPI3KC3 displayed high similarity to yellow catfish's (Tachysurus fulvidraco) PI3KC3. The tissue expression profile revealed that the mRNA levels of CcPI3KC3 in the liver, spleen, and head kidney were significantly greater than those in the brain, heart, intestines, gills, eyes, testes, and ovaries of common carp. We compared the expression patterns of CcPI3KC3 between "Longke-11" mirror carp (CyHV-3-resistant carp) and German mirror carp (non-resistant to CyHV-3) at different times (0, 48, 96, 144 h, 192, 240, 288 h post-infection (hpi)) after CyHV-3 infection. The results revealed that CcPI3KC3 mRNA expression significantly increased in the early infection stage. In the CyHV-3-resistant mirror carp variety, the relative expression of CcPI3KC3 was significantly greater at 48, 96, and 144 hpi compared with the nonbreeding strain groups after infection (p < 0.001). These results indicate that the full-length CcPI3KC3 sequence was successfully cloned from common carp for the first time, and it might play an important role in the immune system of common carp against CyHV-3 infection. This study provides a theoretical basis for the molecular mechanism of CyHV-3 resistance.

Chili (Capsicum annuum) consumption is often suggested, and using functional food cultivars is the most effective strategy post COVID-19 pandemic. Controlling chili breeding activity is one of the most effective methods to produce new hybrid varieties. However, the general combining ability (GCA), specific combining ability (SCA), and heterotic effect of functional biochemicals (polyphenol content, antioxidant activities, and α-glucosidase inhibitory compounds) remain poorly known in C. annuum. This study aimed to estimate these parameters in C. annuum by using five different genotypes and their hybrid combinations based on growth characteristics, yield, yield components, and fruit functional biochemicals. The F1 and F1R progenies were obtained from crosses in a greenhouse with a full diallel mating design. Each parent used in this study had a GCA advantage for each characteristic. The hybrid combination of IPB074 × IPB005 and IPB435 × IPB367 displayed the best yield results. However, the results indicated the opposite regarding α-glucosidase inhibitory compounds. The heterotic effect of functional biochemicals was observed for traits related to genotypes, polyphenol content, antioxidant activity, α-glucosidase inhibitory compounds, and similar properties related to yield and yield components, indicating their use in hybrid chili production.

The Special Issue "Advanced Research in Neuroinflammation" offers a rich and diverse collection of studies that deepen our understanding of how inflammatory mediators are involved in various neurological conditions [...].

Neurodegenerative disorders, particularly Alzheimer's and Parkinson's diseases, continue to challenge modern medicine despite therapeutic advances. Orphan G-protein-coupled receptors (GPCRs) have emerged as promising targets in the central nervous system, offering new avenues for drug development. This review focuses on the structural biology of orphan GPCRs implicated in these disorders, providing a comprehensive analysis of their molecular architecture and functional mechanisms. We examine recent breakthroughs in structural determination techniques, such as cryo-electron microscopy and X-ray crystallography, which have elucidated the intricate conformations of these receptors. The review highlights how structural insights inform our understanding of orphan GPCR activation, ligand binding and signaling pathways. By integrating structural data with molecular pharmacology, we explore the potential of structure-guided approaches in developing targeted therapeutics toward orphan GPCRs. This structural-biology-centered perspective aims to deepen our comprehension of orphan GPCRs and guide future drug discovery efforts in neurodegenerative disorders.

Burn injuries, which significantly affect global public health, require effective treatment strategies tailored to varying severity. Fungi are considered a sustainable, easily propagated source for lead therapeutic discovery. In this study, we explored the burn wound healing potential of Aspergillus terreus through a combination of in vitro, in vivo, metabolite profiling, and in silico analysis. The in vitro scratch assays performed with human skin fibroblast cells showed promising wound healing activity. Furthermore, the burn-induced rats model showed a marked improvement in cutaneous wound healing, evidenced by an accelerated rate of wound closure and better skin regeneration after A. terreus extract treatment at 14 days. The results of this study demonstrated significant enhancements in wound closure and tissue regeneration in the treated rat model, surpassing the outcomes of standard treatments. This controlled healing process, evidenced by superior collagen synthesis and angiogenesis and confirmed by histopathological studies, suggests that A. terreus has potential beyond the traditionally studied fungal metabolites. The metabolite profiling of 27 bioactive compounds was further investigated by docking analysis for the potential inhibition of the NF-κB pathway, which has an important function in inflammation and wound repair. The compounds eurobenzophenone A (7), aspernolide D (16), asperphenalenone A (23), aspergilate D (15), kodaistatin A (18), and versicolactone A (14) showed the highest binding affinity to the target protein with a pose score of -16.86, -14.65, -12.65, -12.45, -12.19, and -12.08 kcal/mol, respectively. Drug-likeness properties were also conducted. The findings suggest the potential wound healing properties of A. terreus as a source for lead therapeutic candidate discovery.

Multiple sclerosis (MS) is a chronic neurodegenerative disease characterized by immune-mediated inflammation and neurodegeneration in the central nervous system (CNS). In this study; we aimed to investigate the gene expression and plasma protein levels of three neuroprotective genes-heat shock proteins (HSP90 and HSP60) and glial cell line-derived neurotrophic factor (GDNF)-in MS patients compared to healthy controls. Forty patients with relapsing-remitting MS and 40 healthy volunteers participated in this study. Gene expression was measured using reverse transcription quantitative real-time PCR, and protein levels were assessed via ELISA. The results showed a significant increase in HSP90 (1.7-fold) and HSP60 (2-fold) gene expression in MS patients compared to controls, along with corresponding increases in protein levels (1.5-fold for both HSP90 and HSP60). In contrast, GDNF gene expression and protein levels were significantly reduced in MS patients, with a 7-fold decrease in gene expression and a 1.6-fold reduction in protein levels. Notably, a non-linear relationship between GDNF gene expression and protein concentration was observed in MS patients, suggesting complex regulatory mechanisms influencing GDNF in the disease. The upregulation of HSP90 and HSP60 in MS highlights their roles in immune regulation and stress responses, while the reduction in GDNF indicates impaired neuroprotection. These findings suggest that HSP90, HSP60, and GDNF could serve as biomarkers for disease progression and as potential therapeutic targets in MS, offering promising avenues for future research and treatment development.

Metamorphosis control is pivotal in preventing the outbreak of jellyfish, and it is often studied using common model organisms. The widespread use of the ultraviolet blocking agent homosalate in cosmetics poses a threat to marine ecosystems. Although the impact of homosalate on marine organisms has been extensively examined, there is a notable absence of research on its effects on jellyfish metamorphosis and the underlying mechanisms, warranting further investigation. In this study, we first established a study model by using 5-methoxy-2-methylindole to induce Aurelia coerulea metamorphosis, and selected homosalate as a PI3K agonist and an ERK agonist, while we used YS-49 as a specific PI3K agonist, as well as ERK knockdown, to observe their effect on the metamorphosis of Aurelia coerulea. The results showed that an Aurelia coerulea metamorphosis model was established successfully, and the PI3K agonist homosalate, YS-49, and the knockdown of ERK molecules could significantly delay the metamorphosis development of Aurelia coerulea. We propose that activating PI3K/Akt and inhibiting the ERK pathway are involved in the delayed development of Aurelia coerulea, which provides a new strategy for the prevention and control of jellyfish blooms.

Fusarium solani KMZW-1 is recognized for its potential as a biocontrol agent against agricultural and forestry pests, particularly due to its compatibility with integrated pest management (IPM) strategies. This study aimed to investigate the complete genome of F. solani KMZW-1 and assess its pathogenicity against Bactrocera dorsalis. Whole-genome sequencing revealed a genome size of 47,239,278 bp, comprising 27 contigs, with a GC content of 51.16% and fungus identified as F. solani KMZW-1. The genome completeness was assessed as 97.93% using BUSCO analysis, the DFVF sequence identifier was Fusarium 0G092560.1, and AntiSMASH analysis identified 35 gene clusters associated with secondary metabolite biosynthesis, providing insights into the genetic basis of its pathogenic mechanisms and biocontrol potential. Comparative genomic analysis found 269 unique genes for F. solani KMZW-1, and collinearity analysis exhibited a high degree of synteny with Fusarium solani-melongenae. The pathogenicity of F. solani KMZW-1 was assessed using concentrations ranging from 1 × 10⁴ to 1 × 10¹¹ conidia/mL. Higher concentrations (1 × 10¹⁰ to 1 × 10¹¹ conidia/mL) resulted in significantly increased cumulative mortality rates of B. dorsalis adults compared to the control group. Notably, the pathogenicity was higher in male adults than in females. Probit analysis yielded LC₅₀ (50% lethal concentration) values of 5.662 for female and 4.486 for male B. dorsalis adults. In summary, F. solani, KMZW-1 exhibits strong insecticidal activity against B. dorsalis and shows potential as a biocontrol agent with IPM strategies. These findings provide robust genomic evidence supporting the use of F. solani KMZW-1 in managing against B. dorsalis populations.

This study investigated the effects of acupuncture and warm acupuncture on the expression and mechanism of the AMP-activated protein kinase (AMPK) signalling pathway associated with lipid accumulation in the liver tissue of rats with metabolic dysfunction-associated fatty liver disease (MAFLD) induced by a high-fat diet. Sprague-Dawley rats were categorised into four groups: control (CON), untreated MAFLD (MAFLD), and two MAFLD groups treated with acupuncture (ACU) and warm acupuncture (WA). The treatment groups underwent 16 application sessions over 8 weeks at the SP9 and BL18 acupoints. We measured the expression levels of AMPK, sterol regulatory element-binding protein1 (SREBP1), acetyl-coenzyme A carboxylase (ACC), peroxisome proliferator-activated receptorα (PPARα), carnitine palmitoyltransferase1 (CPT1), and CPT2. AMPK was activated in both ACU and WA groups. WA downregulated both SREBP1 and ACC expression at the protein level, whereas the acupuncture treatment downregulated SREBP1 expression. Additionally, WA selectively induced the activation of signalling pathways related to AMPK, PPARα, CPT1, and CPT2 at the mRNA level. Histological observations confirmed that fat accumulation was reduced in both the ACU and the WA groups compared to the MAFLD group. The WA treatment-promoted amelioration of HFD-induced MAFLD may be related to the activation of the AMPK/SREBP1/ACC pathway in the liver.

Hypermobile Ehlers-Danlos syndrome (hEDS) is a connective tissue disorder marked by joint hypermobility, skin hyperextensibility, and tissue fragility. Recent studies have linked hEDS with mast cell activation syndrome (MCAS), suggesting a genetic interplay affecting immune regulation and infection susceptibility. This study aims to decode the genetic basis of mast cell hypersensitivity and increased infection risk in hEDS by identifying specific genetic variants associated with these conditions. We conducted whole-genome sequencing (WGS) on 18 hEDS participants and 7 first-degree relatives as controls, focusing on identifying genetic variants associated with mast cell dysregulation. Participants underwent clinical assessments to document hEDS symptoms and mast cell hypersensitivity, with particular attention to past infections and antihistamine response. Our analysis identified specific genetic variants in MT-CYB, HTT, MUC3A, HLA-B and HLA-DRB1, which are implicated in hEDS and MCAS. Protein-protein interaction (PPI) network analysis revealed significant interactions among identified variants, highlighting their involvement in pathways related to antigen processing, mucosal protection, and collagen synthesis. Notably, 61.1% of the hEDS cohort reported recurrent infections compared to 28.5% in controls, and 72.2% had documented mast cell hypersensitivity versus 14.2% in controls. These findings provide a plausible explanation for the complex interplay between connective tissue abnormalities and immune dysregulation in hEDS. The identified genetic variants offer insights into potential therapeutic targets for modulating mast cell activity and improving patient outcomes. Future research should validate these findings in larger cohorts and explore the functional implications of these variants to develop effective treatment strategies for hEDS and related mast cell disorders.