Apmis最新文献

Antimicrobial resistance in Klebsiella pneumoniae (KP) has become a major global public health threat. Allicin, a natural antimicrobial agent, has demonstrated antibacterial activity against KP, but its effect on drug resistance remains unclear. To investigate whether allicin can weaken KP's resistance to meropenem (MEM) and reveal its synergistic mechanism, this study treated KP strains with gradient concentrations of MEM. Resistant strains were identified using the broth microdilution method and viable bacterial counting. Checkerboard assay, time-kill kinetics and isobologram analyses were used to analyse the antibacterial effect of different concentrations of allicin and MEM combined treatment. Molecular docking and cellular thermal shift assay (CETSA) were employed to evaluate the binding of allicin to carbapenemase and efflux pump-related proteins. A mouse model of KP pneumonia was established to investigate the therapeutic effect of allicin combined with MEM. Compared with MEM monotherapy, allicin + MEM acted synergistically, lowering the effective MEM dose by targeting carbapenemase and efflux pumps and mitigating KP-induced pneumonia. This study suggests that the combination of allicin and MEM may be a potential method for reducing bacterial resistance and exerting antibacterial efficacy.

Humans host between 10 and 100 trillion microbial cells, engaging in a mutually beneficial relationship with their microbiota. This intricate ecosystem supports both the microbes and their hosts, provided the body remains in good health. Estimates indicate that the human microbiota comprises over 1000 unique species of microorganisms, which play a crucial role in maintaining immune balance. They help modulate responses to harmless antigens and maintain the integrity of the intestinal mucosal barrier. When the gut microbiota becomes disrupted, a condition known as dysbiosis, it can lead to a range of immune disorders, including autoimmune diseases. Dysbiosis can influence the development and progression of inflammatory and autoimmune conditions by affecting immune system function and inflammatory responses. The present study aims to provide a comprehensive analysis of the relationship between microbiota and autoimmune diseases. It delves into how microbiota imbalances can contribute to autoimmune conditions and explores the underlying mechanisms involved. By integrating recent research and data, this study seeks to enhance our understanding of the microbiota's impact on autoimmune disease mechanisms and offer insights into potential therapeutic strategies.

Streptococcus pneumoniae, which imposes the highest burden on children under 2 years of age, immunocompromised individuals and the elderly in developing countries, causes a range of diseases including pneumonia, meningitis, bacteraemia and septicaemia. Its virulence is driven by an array of surface proteins categorised into four families: non-classical surface proteins, LPXTG-sequence proteins, lipoproteins and choline-binding proteins. The different choline-binding proteins include LytA, LytB, LytC, PspA, CbpA, CbpD, CbpL and CbpF, each with varying numbers of choline-binding repeats in their domains. This review focuses on β-endo-acetylglucosaminidase (LytB), a non-autolytic peptidoglycan hydrolase, emphasising its pivotal role in the pathogenic mechanisms of S. pneumoniae. LytB, with its multiple functional domains (CB, SH3B, WW and GH73), facilitates adhesion to host tissues, promoting initial colonisation, immune evasion and subsequent bacterial dissemination. These functions enable the bacterium to establish invasive diseases. LytB's interactions with host cells and extracellular matrix components underscore its importance in S. pneumoniae pathogenicity. In summary, LytB is a multifaceted choline-binding protein critical to pneumococcal virulence. A detailed understanding of its mechanisms and domain-specific interactions offers promising avenues for the development of novel chemical and plant-based therapeutic strategies, including drugs and vaccines, to combat pneumococcal infections.

Acute coronary syndrome (ACS) is a high-risk disease among cardiovascular diseases. This study is to screen for lncRNA ceRNA regulatory network in acute coronary syndrome associated with percutaneous coronary intervention (PCI) and to validate the XIST/miR-212-3p/CALCOCO2/OPTN axes. lncRNA, miRNA, and mRNA expression microarray data were retrieved and downloaded from the GEO database. Dysregulated lncRNAs and miRNAs were collected using the GEO database. Target genes were predicted and subjected to KEGG pathway analysis. The serum levels of lncRNA XIST, miR-212-3p, CALCOCO2, and OPTN were detected by RT-qPCR. The H9C2 hypoxia-reoxygenation (H/R) injury model was established. The cell viability was detected. The related indicators of mitophagy were detected by flow cytometry and Western blot. Six PCI-related lncRNAs were identified in ACS, linked to 44 PCI-associated miRNAs and 159 PCI-associated mRNAs. KEGG pathway analysis suggested the mitophagy pathway, which involved XIST/miR-212-3p/CALCOCO2/OPTN axes. The levels of XIST, CALCOCO2, and OPTN were increased while the level of miR-212-3p was decreased in PCI patients. Taken together, our results suggest that lncRNA-miRNA-mRNA networks associated with PCI in ACS were presented. In the H/R cell model, XIST promoted mitophagy through miR-212-3p/CALCOCO2/OPTN. XIST can promote mitophagy through the miR-212-3p/CALCOCO2/OPTN axis, thereby alleviating myocardial cell injury.

Burkholderia pseudomallei is a deadly bacterium responsible for melioidosis, which is challenging to treat because of its antibiotic resistance and ability to evade the immune response. This study is focused on in silico analysis to identify novel drug targets. The B. pseudomallei K96243 strain, we have identified seven pathogenicity islands with 138 genes. Subsequent filtering based on criteria such as the data present, essentiality, lack of human homology, and uniqueness narrowed this to 24 promising targets, with eight top candidates. These include proteins involved in energy production (ctaB, BPSL1454, BPSS0086, petB, BPSL1260 and BPSL1259), immune evasion (BPSL1655 and BPSS1780), and the porin efflux pump. Computational interaction analysis revealed a connection between these targets and human immune and respiratory pathways. Prominently, all eight potential drug target candidates showed no homology to human proteins, highlighting their promising role in drug development against melioidosis. This work provides an important framework for identifying novel therapeutics and vaccines against B. pseudomallei.

Many pathogens have evolved capabilities for maintaining chronic infections by entering one or more stages of latency to avoid immune system detection and attack. Several latent pathogens are capable of periodic reactivations decades after their initial infections. However, other pathogens have not evolved intrinsic capabilities for latency to maintain chronic infections, but several of these pathogens can maintain chronic infections by what herein will be called “quasi-latency” in response to suppressions or nutrient deprivation. When later events reduce such suppressions, the quasi-latent pathogens can achieve “resurgent” infections. These quasi-latent pathogens can quickly achieve resurgent infections, which are severe and frequently lethal. This raises the question of how some pathogens can be suppressed into quasi-latency, and how they can become resurgent. Besides innate and adaptive immune cell actions that kill pathogens or pathogen-infected cells, pathogens can be suppressed by nutritional deprivation. Iron deprivation is frequently effective, since iron is essential for pathogens. For instance, hemolytic protozoan parasite infections can provide heme and iron for the resurgence of quasi-latent, iron-deprived pathogens. This could explain the pathogenesis of two puzzling, sometimes lethal pregnancy disorders, pre-eclampsia and eclampsia, which have caused the deaths of millions of women for centuries.

We aimed to characterize the distribution of respiratory pathogens and antimicrobial resistance profiles in children with lower respiratory tract Mycoplasma pneumoniae pneumonia (MPP) and to identify clinical factors associated with multidrug-resistant (MDR) infection. A retrospective analysis of 125 pediatric MPP patients was conducted. Microbiological identification and antimicrobial susceptibility testing were performed on bronchoalveolar lavage fluid isolates. Based on susceptibility results, patients were categorized into an MDR group (n = 25) and a non-MDR group (n = 100). Multivariate logistic regression identified independent predictors of MDR infection. Among Gram-negative isolates, Klebsiella pneumoniae had the highest resistance to cefotaxime (40%), Escherichia coli to piperacillin (50%), and Pseudomonas aeruginosa to aztreonam (54%). For Gram-positive bacteria, resistance to penicillin was most pronounced in Staphylococcus aureus (76%) and Streptococcus pneumoniae (83%). Staphylococcus epidermidis showed elevated resistance to clindamycin, levofloxacin, and penicillin (43% each). Multivariate analysis identified prolonged hospitalization (≥ 14 days), antibiotic exposure for ≥ 7 days, and invasive respiratory procedures as independent risk factors for MDR infection (p < 0.05). Co-isolated bacterial pathogens from children with lower respiratory tract MPP show notable antimicrobial resistance. Routine pathogen testing and susceptibility profiling are crucial for guiding targeted therapy and curbing multidrug resistance.

This study identified miR-5701 and TP53 through bioinformatics analysis utilizing the GEO, GeneCards, and miRDB databases. The serum expression levels were quantified via Reverse Transcription Quantitative Real-time Polymerase Chain Reaction (RT-qPCR). The binding relationship between miR-5701 and TP53 was confirmed using dual luciferase reporter assays. Subsequently, MC3T3-E1 cell differentiation was induced with Bone Morphogenetic Protein 2 (BMP2), and the expression changes of miR-5701 and TP53 after cell differentiation were detected. Subsequently, after overexpression of miR-5701 and TP53, the expression levels of key osteogenic differentiation markers Alkaline Phosphatase (ALP), Osteocalcin (OCN), and type I collagen were evaluated by ELISA. Serum miR-5701 expression is downregulated in osteoporotic fracture patients, while it increases after osteoblast differentiation. TP53 is a negative regulatory binding factor downstream of miR-5701. The mRNA expression of TP53 in the patient serum and the differentiated osteoblast cells is exactly opposite to that of miR-5701. Overexpression of miR-5701-mediated promotion of osteoblast proliferation and differentiation can be reversed by TP53. miR-5701 was found to facilitate osteoblast proliferation and differentiation through negative regulation of the target gene TP53 expression, suggesting that miR-5701 could serve as a promising therapeutic target for promoting fracture healing.