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The composition of the gut microbiota varies among end-stage renal disease (ESRD) patients on the basis of their mode of renal replacement therapy (RRT), with notably more pronounced dysbiosis occurring in those undergoing hemodialysis (HD). Interventions such as dialysis catheters, unstable hemodynamics, strict dietary restrictions, and pharmacotherapy significantly alter the intestinal microenvironment, thus disrupting the gut microbiota composition in HD patients. The gut microbiota may influence HD-related complications, including cardiovascular disease (CVD), infections, anemia, and malnutrition, through mechanisms such as bacterial translocation, immune regulation, and the production of gut microbial metabolites, thereby affecting both the quality of life and the prognosis of patients. This review focuses on alterations in the gut microbiota and its metabolites in HD patients. Additionally, understanding the impact of the gut microbiota on the complications of HD could provide insights into the development of novel treatment strategies to prevent or alleviate complications in HD patients.

Diabetic nephropathy (DN) is a major microvascular complication of both type 1 and type 2 diabetes mellitus and is the most frequent cause of end-stage renal disease with an increasing prevalence. Presently there is no non-invasive method for differential diagnosis, and an efficient target therapy is lacking. Extracellular vesicles (EV), including exosomes, microvesicles, and apoptotic bodies, are present in various body fluids such as blood, cerebrospinal fluid, and urine. Proteins in EV are speculated to be involved in various processes of disease and reflect the original cells’ physiological states and pathological conditions. This systematic review is based on urinary extracellular vesicles studies, which enrolled patients with DN and investigated the proteins in urinary EV. We systematically reviewed articles from the PubMed, Embase, Web of Science databases, and China National Knowledge Infrastructure (CNKI) database until January 4, 2022. The article quality was appraised according to the Newcastle-Ottawa Quality Assessment Scale (NOS). The methodology of samples, isolation and purification techniques of urinary EV, and characterization methods are summarized. Molecular functions, biological processes, and pathways were enriched in all retrievable urinary EV proteins. Protein-protein interaction analysis (PPI) revealed pathways of potential biomarkers. A total of 539 articles were retrieved, and 13 eligible records were enrolled in this systematic review and meta-analysis. And two studies performed mass spectrometry to obtain the proteome profile. Two of them enrolled only T1DM patients, two studies enrolled both patients with T1DM and T2DM, and other the nine studies focused on T2DM patients. In total 988 participants were enrolled, and DN was diagnosed according to UACR, UAER, or decreased GFR. Totally 579 urinary EV proteins were detected and 28 of them showed a potential value to be biomarkers. The results of bioinformatics analysis revealed that urinary EV may participate in DN through various pathways such as angiogenesis, biogenesis of EV, renin-angiotensin system, fluid shear stress and atherosclerosis, collagen degradation, and immune system. Besides that, it is necessary to report results compliant with the guideline of ISEV, in orderto assure repeatability and help for further studies. This systematic review concordance with previous studies and the results of meta-analysis may help to value the methodology details when urinary EV proteins were reported, and also help to deepen the understanding of urinary EV proteins in DN.

ABSTRACT The characterization of Treponema pallidum proteins is of great significance for the study of the prevention, diagnosis, and pathogenesis of syphilis. The structures and functions of many T. pallidum proteins, including the Tp40 (Tp0134) protein, remain unknown. To explore the expression pattern of the Tp40 protein within T. pallidum, we established an animal model of syphilis infection to compare the variations in serum Tp40 antibody levels between Live and Inactivated Tp groups. The results indicated that the absorbance of Tp40-enzyme-linked immunosorbent assay (ELISA) did not increase in the Inactivated group and the Untreated group, but it increased in the Live Tp infection group, suggesting that the Tp40 protein is an in vivo-induced antigen that is only actively expressed during infection. In addition, the localization of the Tp40 protein was determined by the gel microdrop method. We found that Tp40 may be a transmembrane protein with a signaling peptide present in the intima periplasm of T. pallidum. Finally, 468 patients’ sera were collected for diagnostic value evaluation. Tp40-ELISA, LZ-ELISA, and Shanghai Kehua rapid plasma reagin (RPR) reagent kit showed a high degree of consistency in 468 serum samples. This suggests that Tp40 could be a valuable diagnostic antigen. The results of this study provide a new reference for the study of the pathogenesis, protein function, and diagnosis of syphilis.IMPORTANCEIn recent years, syphilis, as a chronic infectious disease, has once again attracted much attention. Treponema pallidum exhibits remarkable infectivity, concealment, and aggressiveness, posing considerable challenges to its prevention and control. The underlying pathogenic mechanisms remain elusive, and during the infection process, the roles of numerous proteins are still unclear. Through protein characterization in this study, it was found that the Tp40 protein is highly likely to be a transmembrane protein with a signal peptide and may be located in the periplasm. Besides, based on experiments with animal models and the detection of human serum samples, we believe that the Tp40 protein is a potential in vivo-induced antigen of T. pallidum that can be used for serological diagnosis of syphilis. This study conducted a preliminary exploration of the Tp40 protein and provided a meaningful reference for further exploration of the functional mechanism of the Tp40 protein and its significance in clinical diagnosis.

ABSTRACT Treponema pallidum (T. pallidum), the pathogen of syphilis, can invade organisms through mucous membranes or broken skin and proliferate in the host. It spreads rapidly and causes chronic systemic multi-organ damage. Currently, the invasion and pathogenesis of T. pallidum remain a mystery. In this study, we established a T. pallidum infection model in New Zealand rabbits, and the T. pallidum burden in various tissues and organs was detected to investigate the dynamic spread of T. pallidum in different organs. Our results indicated that the T. pallidum burden in rabbits was in a cyclic and repeated dynamic process of decreasing and increasing after infection. In addition, the localization of lipoprotein Tp0971 was confirmed by using the gel microdroplet method. We found that Tp0971 might be a membrane lipoprotein that exists in the inner and outer membranes of T. pallidum. The immune-protective effect of the T. pallidum infection-dependent antigen Tp0971 was evaluated. Tp0971/CpG can induce high levels of Tp0971-specific antibodies, delay skin damage, and promote healing at the infected sites of T. pallidum in New Zealand rabbits. This indicated that Tp0971 may serve as a vaccine antigen candidate. Our results provide new ideas for future research on the proliferation, spread mechanism, and vaccine development of T. pallidum. IMPORTANCE The past two decades have seen a worldwide resurgence in infections caused by Treponema pallidum (T. pallidum) subsp. pallidum, the syphilis spirochete. The well-recognized capacity of the syphilis spirochete for early dissemination and immune evasion has earned it the designation “the stealth pathogen.” There are many hurdles to studying syphilis pathogenesis, most notably the difficulty of culturing and genetically manipulating T. pallidum, as well as the absence of an effective vaccine for T. pallidum prevention. T. pallidum infection in humans is a complex and lengthy process. In this study, we investigated the invasion process and the function of the infection-dependent antigen Tp0971 as an immunogen to inhibit the dissemination of T. pallidum in an animal infection model. This enables a better understanding of the specific pathogenic mechanism of this pathogen, syphilis pathogenesis, and vaccine research.

The data presented in this article are related to the research article entitled “Performance of novel infection phase-dependent antigens in syphilis serodiagnosis and treatment efficacy determination”. The rabbit model [1,2] is an appropriate animal model for studying syphilis, a classic sexually transmitted disease (STD). Live Treponema pallidum (T. pallidum, Tp) and inactivated T. pallidum were inoculated in the backs of New Zealand rabbits. RT-PCR was performed to determine whether T. pallidum DNA could be detected in different groups. Sixty paired serum samples from patients at follow-up were tested by RPR and recombinant Tp0971-, Tp0768-, Tp0462- and Tp92-based ELISA. Keywords: Treponema pallidum, Rabbit, RPR, ELISA