Apmis最新文献

The gut microbiota (GM) has emerged as an important element in the management of host metabolism, immune functions, and overall metabolic well-being. This review consolidates contemporary research regarding the intricate relationship between GM and diabetes mellitus, focusing on the mechanisms by which microbial composition and activity affect the development of both Type 1 (T1D) and Type 2 diabetes (T2D). Dysbiosis—characterized by diminished microbial diversity, a modified Firmicutes/Bacteroidetes ratio, and a reduction in advantageous SCFA-producing bacteria—has been significantly associated with disrupted glucose metabolism, insulin resistance, and persistent inflammation. Additionally, the review discusses the potential for microbial signatures and metabolites, such as SCFAs, lipopolysaccharides (LPS), and trimethylamine N-oxide (TMAO), to serve as novel biomarkers for early detection and risk evaluation. Moreover, it investigates therapeutic approaches designed to reestablish microbial balance through the use of probiotics, prebiotics, dietary changes, fecal microbiota transplantation (FMT), and microbiome engineering. By integrating findings from recent research, this paper emphasizes the groundbreaking possibilities of microbiome-centric diagnostics and treatments in individualized diabetes care.

Transcription factor TCF21 is downregulated in lung adenocarcinoma (LUAD), contributing to poor treatment outcomes. This study explores its role in regulating CD8⁺ T cell-mediated antitumor immunity and metastasis. TCF21 expression was analyzed via TCGA. Downstream target ERO1A was identified using JASPAR prediction, validated by dual-luciferase/ChIP assays. LUAD mouse models and cell experiments (Transwell, flow cytometry, LDH/ELISA) assessed impacts on metastasis and CD8⁺ T cell function. The results showed that TCF21 overexpression inhibited LUAD migration/invasion and enhanced CD8⁺ T cell cytotoxicity. Mechanistically, TCF21 repressed ERO1A transcription, reducing IDO1 expression. Conversely, ERO1A overexpression promoted metastasis and suppressed CD8⁺ T cell activity via IDO1 upregulation. Knockdown of ERO1A or IDO1 blockade reversed the pro-tumor effects of TCF21 loss. In conclusion, TCF21 downregulation in LUAD activates the ERO1A-IDO1 axis, enabling immune escape from CD8⁺ T cell killing and accelerating malignancy.

Methicillin-resistant Staphylococcus aureus (MRSA) is reported to cause serious health issues in humans by exploiting its biofilm network. To combat this global concern, the combined efficacy of cuminaldehyde (a bioactive phytochemical) and vancomycin (an antibiotic) was tested against MRSA strains. While both compounds exhibited independent antibacterial activity, their combination revealed improved efficacy against MRSA through additive interactions. Response surface methodology (RSM)-generated quadratic models optimized the combinatorial doses, revealing significant microbial growth inhibition of the MRSA strains (p < 0.05). Furthermore, the combined application of cuminaldehyde and vancomycin at sub-MIC doses could inhibit biofilm formation by lowering bacterial adhesion, extracellular polysaccharide (EP) synthesis and the extent of biofilm-associated proteins. Additionally, the mechanistic studies revealed that the said combination (cuminaldehyde and vancomycin) was found to accumulate oxidative stress with a ~2.5-fold increase in intracellular reactive oxygen species (ROS) and a ~2.3-fold reduction in membrane integrity. In view of the same, this combination attenuated key virulence factors (protease, hemolysin, and coagulase) and metabolic activity of MRSA. Hence, the combinations involving cuminaldehyde and vancomycin could potentially enhance the antimicrobial and antibiofilm efficacy, presenting a promising approach to combat the escalating crisis linked with MRSA-associated threats.

This review summarizes key clinical findings on probiotics in addressing bacterial vaginosis (BV) and sexually transmitted diseases (STDs) in women. Lactobacillus bacteria play a critical role in maintaining a balanced vaginal microbiome by supporting an acidic environment and helping combat conditions like BV, AIDS, maternal group B Streptococcus (GBS), and candidiasis. Probiotics, either alone or combined with antibiotics, have shown promise in promoting microbiome recovery and potentially reducing recovery time. However, their efficacy depends on the strains used and specific conditions, emphasizing the need for further research. Additionally, probiotics can mitigate risks associated with excessive antibiotic use, including antibiotic resistance. The increasing interest in probiotics for women's sexual health has led to the development of specialized products, though identifying superior strains and optimal dosages remains an ongoing challenge. In conclusion, probiotics offer a non-invasive and cost-effective approach to supporting women's health by promoting microbiota balance and enhancing immune function. They offer a promising strategy for managing BV and potentially reducing STD risks. However, further research is necessary to standardize strains, dosages, and application methods in order to achieve consistent and effective outcomes.

Leptospira interrogans, known for its association with environmental biofilms, poses significant challenges in managing leptospirosis due to its persistent virulence and resistance to antimicrobial agents. Addressing the biofilms in infection and resistance necessitates novel anti-leptospiral agents and strategies, with bioactive compounds offering better biomolecules to combat leptospiral biofilms. This study investigates the role of eugenol against L. interrogans, which has been unexplored. In this study, we have evaluated the impact of eugenol on the growth and biofilm formation of L. interrogans. Eugenol inhibited 70% of biofilm formation at its MBIC70 (10 mM). These findings were further validated through fluorescence and scanning electron microscopy to assess cell viability and morphological changes. Furthermore, the expression levels of key genes, csrA and lipL32, associated with bacterial growth and biofilm formation, were analyzed using qRT-PCR. To complement these findings, molecular docking, c-DFT, and ADME profiles were performed to investigate the interaction of eugenol with the transpeptidase/penicillin-binding protein. The results strongly correlate with the biological outcomes observed in the experimental studies, supporting the efficacy of eugenol against L. interrogans.

The rapid emergence of antimicrobial resistance, particularly among multidrug-resistant bacteria (MDRB) and biofilm-associated infections, poses a critical public health threat. In this study, a multifunctional nanocomposite with enhanced antibiofilm potential was developed by integrating zinc oxide nanoparticles (ZnO NPs) into a bacterial cellulose (BC)-based scaffold. ZnO NPs, synthesized via the co-precipitation method, displayed uniform spherical morphology and were comprehensively characterized using UV–Vis, FTIR, FE-SEM, EDS, XRD, and DLS analyses. A composite nanofiber matrix was fabricated by electrospinning a chitosan (CS)/polyvinyl alcohol (PVA) blend containing ZnO NPs onto BC, yielding structurally stable BC-PVA-CS-ZnO nanofibers (NFs). Both ZnO NPs and nanofibers exhibited antioxidant activity (30.42% and 34.54%, respectively), and hemocompatibility, confirming their biocompatible nature. Antibacterial studies against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa revealed significant bacterial inhibition, while biofilm assays demonstrated disruption rates of 29.5% (ZnO NPs) and 24.4% (nanofibers), respectively, against P. aeruginosa. The synergistic integration of ZnO with CS/PVA and BC effectively disrupted extracellular polymeric substances (EPS) and suppressed MDR biofilms. Owing to its structural integrity, biodegradability, and tissue compatibility, the engineered nanocomposite demonstrates strong potential as an alternative to conventional antibiotics for wound management and prevention of biofilm-related resistant infections.

Dental caries, a significant global health concern, is intricately linked to the development and persistence of cariogenic biofilms on tooth surfaces. These complex microbial ecosystems orchestrate a multifactorial process of decay, adhering to teeth, producing acids that erode enamel, and exhibiting resistance to traditional therapies. This review delves into the intricate mechanisms of cariogenic biofilm formation and pathogenesis, exploring adhesion, acid production, extracellular polymeric substance (EPS) mediated acid tolerance, and nutrient acquisition within the biofilm. We then explore novel strategies for disrupting these biofilms, including next-generation antimicrobials, anti-adhesion molecules, biofilm-dispersing enzymes, and the potential of probiotics and prebiotics. Finally, the review examines promising future directions in oral disease treatment, highlighting the potential of personalized medicine, biofilm-modifying enzymes and peptides, host modulation strategies, and the development of combination therapies and advanced delivery systems for enhanced biofilm control. Understanding the mechanisms of cariogenic biofilms and exploring innovative treatment strategies could pave the way for more effective prevention and management of dental caries.

Antimicrobial-resistant Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA), is an increasing concern in dairy production. Using a One Health approach, this cross-sectional study assessed the prevalence, antimicrobial resistance (AMR) profiles, and biofilm-forming ability of S. aureus from pooled bovine milk, animal handler hand swabs, and herd slurry collected from 405 farms across Punjab, India. The prevalence of coagulase-positive S. aureus was highest in hand swabs (43.7%), followed by milk (30.1%) and slurry (17.5%). Phenotypic resistance varied by source: milk isolates showed the greatest resistance to cefoxitin (37.7%) and penicillin (36.9%); hand swab isolates showed resistance to erythromycin (42.9%) and tetracycline (36.7%); and slurry isolates showed resistance to tetracycline (66.2%) and cefoxitin (59.2%). Multidrug resistance (MDR) was found in 45.9% of milk, 60.5% of hand swabs, and 92.9% of slurry isolates. MRSA was detected in 6.6% of milk, 2.8% of hand swab, and 1.4% of slurry isolates, with SCCmec type V as the most common type. Genotypic screening identified blaZ, mecA, tetK, ermC, and aacA-aphD, with the highest genotype–phenotype concordance for tetracycline resistance. Biofilm assays showed 94.9% of isolates formed biofilms; 28.4% were strong producers. MDR milk isolates showed the highest strong biofilm capacity (39.3%). This study underscores the need for integrated AMR surveillance and improved dairy biosecurity.

Dental plaque is a complex microbial biofilm that contributes significantly to the onset of oral diseases and related infections. The initial attachment of primary colonizers to the salivary pellicle, which coats the tooth surface, is a critical first step in plaque development. Primary colonizers use pili on their cell surfaces to facilitate attachment to host surfaces and other bacteria. Pili-mediated adhesion and interbacterial coaggregation promote oral biofilm growth. Recent structural studies of primary colonizers and other oral bacteria have provided new insights into the role of pili in dental plaque formation. Understanding the molecular intricacies of pilus assembly and adhesion paves the way for the development of antiadhesive approaches to control dental plaque formation. Disrupting initial bacterial attachment by targeting pili- and pili-mediated interactions may offer a promising strategy to prevent oral biofilm development and associated infections. This review provides updates on pili and pilus components in oral bacteria, with a focus on the primary colonizers of dental plaque from a structural perspective.