Alterations in the microbiome correlate with improved metabolism in patients following bariatric surgery. While fecal microbiota transplantation (FMT) from obese patients into germ-free (GF) mice has suggested a significant role of the gut microbiome in metabolic improvements following bariatric surgery, causality remains to be confirmed. Here, we perform paired FMT from the same obese patients (BMI > 40; four patients), pre- and 1 or 6 months post-Roux-en-Y gastric bypass (RYGB) surgery, into Western diet-fed GF mice. Mice colonized by FMT from patients' post-surgery stool exhibit significant changes in microbiota composition and metabolomic profiles and, most importantly, improved insulin sensitivity compared with pre-RYGB FMT mice. Mechanistically, mice harboring the post-RYGB microbiome show increased brown fat mass and activity and exhibit increased energy expenditure. Moreover, improvements in immune homeostasis within the white adipose tissue are also observed. Altogether, these findings point to a direct role for the gut microbiome in mediating improved metabolic health post-RYGB surgery.

The existing knowledge about the association between NLRP3 rs35829419/rs10754558 polymorphisms and susceptibility to autoimmune diseases (AIDs) remains controversial. Herein, a meta-analysis was performed to evaluate such association. We searched databases for relevant studies published in English up to February 2021. Stata14 was used to assess the odds ratio (OR). As for NLRP3 rs35829419, no significant association to overall AIDs was found in three genetic models [A vs. C: OR (95%CI) = 0.89 (0.69–1.14); AC vs. CC: 1.00 (0.77–1.30); AA/AC vs. CC: 0.93 (0.71–1.20)]. However, subgroup analysis by disease type showed that NLRP3 rs35829419 A allele may have a significant protective effect on rheumatoid arthritis (RA) susceptibility [A vs. C: 0.74 (0.57–0.96)]. NLRP3 rs10754558 polymorphism contributes to significantly reduce the risk of AIDs in the allelic model [G vs. C: 0.78 (0.71–0.87)], homozygote co-dominant model [GG vs. CC: 0.63 (0.51–0.77)], heterozygote co-dominant model [GC vs. CC: 0.78 (0.66–0.91)], dominant model [GG/GC vs. CC: 0.73 (0.63–0.84)], and recessive model [GG vs. GC/CC: 0.73 (0.62–0.88)]. In the subgroup analysis by ethnicity, association was observed between the NLRP3 rs10754558 G allele and AIDs in Latin Americans, but not in European, Arabian, or Asian populations. Stratification by disease type showed a significant association of the NLRP3 rs10754558 G allele with type 1 diabetes (T1D), RA, and systemic lupus erythematosus (SLE), but not with celiac disease (CD), multiple sclerosis (MS), or myasthenia gravis (MG). This meta-analysis suggests that the NLRP3 rs10754558, but not rs35829419, polymorphism is associated with susceptibility to AIDs, especially in Latin American individuals.

Objective: The aim of this study was to explore the clinical values of combined detection of lipoprotein‐associated phospholipase A2 (Lp‐PLA2), serum amyloid A (SAA), and plasma fibrinogen (FIB) in the diagnosis of acute cerebral infarction (ACI).Methods: A case‐control study including 100 hospitalized patients with ACI and 47 healthy controls was carried out. The level of Lp‐PLA2, SAA, and FIB was detected, respectively, and their clinical values were analyzed. Carotid lesions and neurological impairment were also analyzed in each patient.Results: The level of Lp‐PLA2, SAA, and FIB in the ACI group was significantly higher than that of the controls, and the three biomarkers showed a significant positive correlation and were considered as risk factors for ACI. The area under the curve (AUC) for Lp‐PLA2, SAA, and FIB was 0.858, 0.743, and 0.672, respectively. When three biomarkers were used in combination, the AUC was 0.879. Compared with the other groups, the levels of three biomarkers in bilateral carotid plaque ACI group were all significantly higher. In addition, the level of Lp‐PLA2 and SAA in ACI patients with severe neurological impairment was also significantly higher than that of the mild‐to‐moderate group.Conclusion: Lp‐PLA2 combined with SAA and FIB had a high clinical value for rapid diagnosis and prediction of ACI. These biomarkers were also significantly associated with the formation of bilateral carotid atherosclerotic plaques and the severe neurological impairment in ACI patients.

Objective: To explore the association between lipoprotein-related phospholipase A2 (Lp-PLA2) and the risk of Parkinson’s disease (PD).Methods: A case-control study involving 58 hospitalized PD patients and 60 healthy controls was carried out. Serum Lp-PLA2 level was detected. According to the disease course and severity, PD patients were subdivided to analyze the clinical value of Lp-PLA2. Relationship between Lp-PLA2 and PD risk was analyzed by logistic regression. Diagnostic value of Lp-PLA2 in PD patients was investigated using receiver’s operator characteristic curves.Results: Lp-PLA2 level was significantly higher in the PD patients compared with the controls, and was significantly and positively correlated with the Hoehn-Yahr (H&Y) stage. The serum Lp-PLA2 level and H&Y stage of PD patients with a longer disease course were significantly higher than those with a shorter disease course. PD patients with milder conditions had significantly lower serum Lp-PLA2 levels than patients with severe conditions. Multivariable logistic regression analysis indicated higher Lp-PLA2 level was an independent risk factor of PD patients. Moreover, the area under the curve for Lp-PLA2 was 0.703, which was between those of homocysteine and serum amylase A.Conclusion: To our knowledge, this is the first study to show that increased level of Lp-PLA2 is associated with the risk of PD. Lp-PLA2 may be used for early detection of PD, and provides an effective intervention target for clinical treatment of PD.

The complex etiology and spectrum of kidney diseases necessitate vigilant attention; the focus on early diagnosis and intervention in kidney diseases remains a critical issue in medical research. Recently, with the expanding studies on extracellular vesicles, exosomes have garnered increasing interest as a promising tool for the diagnosis and treatment of kidney diseases. Exosomes are nano-sized extracellular vesicles that transport a diverse array of bioactive substances, which can influence various pathological processes associated with kidney diseases and exhibit detrimental or beneficial effects. Within the kidney, exosomes derived from the glomeruli and renal tubules possess the ability to enter systemic circulation or urine. The biomarkers they carry can reflect alterations in the pathological state of the kidneys, thereby offering novel avenues for early diagnosis. Furthermore, research studies have confirmed that exosomes originating from multiple cell types exhibit therapeutic potential in treating kidney disease; notably, those derived from mesenchymal stem cells (MSCs) have shown significant treatment efficacy. This comprehensive review summarizes the contributions of exosomes from different cell types within the kidneys while exploring their physiological and pathological roles therein. Additionally, we emphasize recent advancements in exosome applications for the diagnosis and treatment of various forms of kidney diseases over the past decades. We not only introduce the urinary and blood biomarkers linked to kidney diseases found within exosomes but also explore their therapeutic effects. Finally, we discuss existing challenges and future directions concerning the clinical applications of exosomes for diagnostic and therapeutic purposes.

Background: Advanced triple-negative breast cancer (TNBC) is prone to brain metastasis (BrM). The precise molecular mechanism responsible for this phenomenon has not yet been completely established, so it is vital to comprehend the molecular mechanism behind it. Methods: The protein chip analysis was conducted to identify any abnormal UBE2T protein expression in TNBC, especially BrM. Here, we used public databases and bioinformatics analysis as well as clinical samples from different cohorts to investigate the interrelationship between UBE2T/CDC42/CD276. This predicted relationship was then repeatedly validated using different in vivo and in vitro experimental methods. Additionally, multiple experimental approaches were implemented, encompassing western blotting, Co-IP, GST pull-down, flow cytometry, mass spectrometry, immunofluorescence, immunohistochemistry, and qRT-PCR to reveal the molecular mechanism of UBE2T-mediated immune escape and BrM. Results: Our results indicate that expressed at elevated levels in breast cancer, UBE2T is negatively linked to patient prognosis, especially in BrM of TNBC. Data from clinical samples from our different cohorts and TCGA indicate a significant correlation between UBE2T and immunosuppression. Mechanistically, UBE2T directly interacts with CDC42, promoting its K48-linked polyubiquitination and proteasomal degradation, thereby inhibiting CDC42 from degrading CD276 via the autophagy-lysosomal pathway, indirectly upregulating CD276 and thereby impairing the CD8⁺ T cells function, ultimately mediating tumor immune escape and BrM. Finally, animal experimental results also showed that inhibition of UBE2T elevated the TNBC sensitivity to immune checkpoint CD276 blockade and inhibited BrM of TNBC. Conclusions: In conclusion, our results indicate a new mechanism whereby UBE2T-mediated ubiquitination positively controls the UBE2T/CDC42/CD276 axis to upregulate tumor cell expression of CD276 and thereby impair CD8⁺ T cells function, ultimately leading to tumor cell immune escape and BrM.