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Background: The gut microbiome is composed of various microorganisms such as bacteria, fungi, and protozoa, and constitutes an important part of the human gut. Its composition is closely related to human health and disease. Alzheimer's disease (AD) is a neurodegenerative disease whose underlying mechanism has not been fully elucidated. Recent research has shown that there are significant differences in the gut microbiota between AD patients and healthy individuals. Changes in the composition of gut microbiota may lead to the development of harmful factors associated with AD. In addition, the gut microbiota may play a role in the development and progression of AD through the gut–brain axis. However, the exact nature of this relationship has not been fully understood. Aims: This review will elucidate the types and functions of gut microbiota and their relationship with AD and explore in depth the potential mechanisms of gut microbiota in the occurrence of AD and the prospects for treatment strategies. Methods: Reviewed literature from PubMed and Web of Science using key terminologies related to AD and the gut microbiome. Results: Research indicates that the gut microbiota can directly or indirectly influence the occurrence and progression of AD through metabolites, endotoxins, and the vagus nerve. Discussion: This review discusses the future challenges and research directions regarding the gut microbiota in AD. Conclusion: While many unresolved issues remain regarding the gut microbiota and AD, the feasibility and immense potential of treating AD by modulating the gut microbiota are evident. [ABSTRACT FROM AUTHOR]

Tigecycline is one of important antimicrobial agents for the treatment of infections caused by multidrug-resistant (MDR) Gram-negative bacteria. However, the emergence and prevalence of plasmid-mediated tigecycline resistance gene tet (X4) are threatening human and animal health. Fitness cost elicited by resistance plasmids is a key factor affecting the maintenance and transmission of antibiotic resistance genes (ARGs) in the host. A comparative analysis of the fitness cost of different types of tet (X4)-positive plasmids is helpful to understand and predict the prevalence of dominant plasmids. In this study, we performed a large-scale analysis of fitness cost of tet (X4)-positive plasmids origin from clinical isolates. These plasmids were successfully electroporated into a reference strain Escherichia coli TOP10, and a series of transformants carrying the tet (X) gene were obtained. The effects of tet (X4)-positive plasmids on the growth rate, plasmid stability, relative fitness, biofilm formation, and virulence in a Galleria mellonella model were evaluated. Consequently, we found that these plasmids resulted in varying degrees of fitness cost on TOP10, including delayed bacterial growth and attenuated virulence. Out of these plasmids, tet (X4)-harboring IncFII plasmids showed the lowest fitness cost on the host. Furthermore, by means of experimental evolution in the presence of commonly used drugs in clinic, the fitness cost of tet (X4)-positive plasmids was substantially alleviated, accompanied by increased plasmid stability. Collectively, our data reveal the differential fitness cost caused by different types of tet (X4)-positive plasmids and suggest that the wide use of tetracycline antibiotics may promote the evolution of plasmids. [ABSTRACT FROM AUTHOR]

The emergence of plasmid-mediated tigecycline resistance gene tet (X4) poses a challenging threat to public health. Based on the analysis of tet (X4)-positive plasmids in the NCBI database, we found that the IncX1-type plasmid is one of the most common vectors for spreading tet (X4) gene, but the mechanisms by which these plasmids adapt to host bacteria and maintain the persistence of antibiotic resistance genes (ARGs) remain unclear. Herein, we investigated the underlying mechanisms of how host bacteria modulate the fitness cost of IncX1 plasmids carrying tet (X4) gene. Interestingly, we found that the tet (X4)-bearing IncX1 plasmids encoding H-NS protein imposed low or no fitness cost in Escherichia coli and Klebsiella pneumoniae ; instead, they partially promoted the virulence and biofilm formation in host bacteria. Regression analysis revealed that the expression of hns gene in plasmids was positively linked to the relative fitness of host bacteria. Furthermore, when pCE2:: hns was introduced, the fitness of tet (X4)-positive IncX1 plasmid pRF55-1 without hns gene was significantly improved, indicating that hns mediates the improvement of fitness. Finally, we showed that the expression of hns gene is negatively correlated with the expression of tet (X4) gene, suggesting that the regulatory effect of H-NS on adaptability may be attributed to its inhibitory effect on the expression of ARGs. Together, our findings suggest the important role of plasmid-encoded H-NS protein in modulating the fitness of tet (X4)-bearing IncX1 plasmids, which shed new insight into the dissemination of tet (X4) gene in a biological environment. [ABSTRACT FROM AUTHOR]

The present study aimed to characterize the effect of microRNA (miR)-367-3p on sevoflurane anesthesia and elucidate the underlying mechanism. A total of 36 4-month-old adult Sprague-Dawley rats were divided into six groups. Sevoflurane was inhaled at concentrations of 0, 1, 2, 4, 8 and 16% for a total of 6 h; the hippocampus of the brain was subsequently minced and digested, and astrocytes were isolated. Various methods, including reverse transcription-quantitative (RT-q)PCR, western blotting and TUNEL staining, were used to determine the expression levels of Bax, BCL-2 and BCL-2-like protein 11 (BCL2L11), as well as the level of apoptosis. The rats were treated with 8% sevoflurane and the astrocytes from the rats were transfected with miR-367-3p or anti-miR-367-3p. The present study demonstrated that sevoflurane promoted astrocytes apoptosis. Western blotting revealed that with an increase of sevoflurane concentration, the expression levels of the apoptotic proteins Bax and BCL2L11 were significantly increased, whereas the protein expression levels of BCL-2 were significantly decreased. However, overexpression of miR-367-3p reversed these effects. TUNEL staining revealed that sevoflurane promoted the apoptosis of astrocytes, while apoptosis was reversed by miR-367-3p overexpression. RT-qPCR demonstrated that sevoflurane inhibited the expression of miR-367-3p. Notably, miR-367-3p reduced the expression of BCL2L11, thereby inhibiting the apoptosis of astrocytes originating from the hippocampal area of adult rats induced by sevoflurane. Therefore, miR-367-3p and BCL2L11 may act as effective targets for the study of anesthesia. [ABSTRACT FROM AUTHOR]

The emergence and prevalence of the tet(X) gene and its variants in the environment and in clinical settings constitute a growing concern for public health worldwide. Accordingly, the tigecycline resistance gene variant tet(X6) is widely detected in Proteus spp. and Acinetobacter spp. rather than Enterobacteriaceae, while the underpinning behind this phenomenon is still unclear. To investigate the mechanisms underlying this distinct phenomenon, we assessed the fitness of the engineered plasmid pBAD-tet(X6) in different host bacteria by monitoring their growth curves, relative fitness and the ability of biofilm formation, as well as virulence in a Galleria mellonella model. MIC and qRT-PCR analysis indicated the successful expression of the tet(X6) gene in these strains in the presence of l-arabinose. Furthermore, we found that pBAD-tet(X6) displayed the lowest fitness cost in P. mirabilis compared with that in E. coli or S. Enteritidis, suggesting the fitness difference of tet(X6)-bearing plasmids in different host bacteria. Consistently, the carriage of pBAD-tet(X6) remarkably reduced the biofilm production and virulence of E. coli or S. Enteritidis. These findings not only indicate that the fitness cost difference elicited by the tet(X6) gene may be responsible for its selectivity in host bacteria but also sheds new insight into the dissemination of antibiotic resistance genes (ARGs) in clinical and environmental isolates. [ABSTRACT FROM AUTHOR]

CD1d-restricted invariant NKT (iNKT) cells play a critical role in tumor immunity. However, the scarcity and limited persistence restricts their development and clinical application. Here, we demonstrated that iNKT cells could be efficiently expanded using modified cytokines combination from peripheral blood mononuclear cells. Introduction of IL-21 significantly increased the frequency of CD62L-positive memory-like iNKT cells. iNKT cells armoring with B7H3-targeting second generation CAR and IL-21 showed potent tumor cell killing activity. Moreover, co-expression of IL-21 promoted the activation of Stat3 signaling and reduced the expression of exhaustion markers in CAR-iNKT cells in vitro . Most importantly, IL-21-arming significantly prolonged B7H3 CAR-iNKT cell proliferation and survival in vivo , thus improving their therapeutic efficacy in mouse renal cancer xerograph models without observed cytokine-related adverse events. In summary, these results suggest that B7H3 CAR-iNKT armored with IL-21 is a promising therapeutic strategy for cancer treatment., Competing Interests: All other authors have no conflict of interest to declare for this research. H.L., J.Z., G.W., Y.L., and Y.D. hold patents in this manuscript secured under the numbers 202110827989.3 and 202110783589.7., (© 2023 The Authors.)