Characterization of the intestinal microbiota in MSM with HIV infection.

BACKGROUND: HIV-infected persons demonstrate notable disturbances in their intestinal microbiota; however, the impact of intestinal microbiota on HIV susceptibility in men who have sex with men (MSM), as well as the effects of HIV and antiretroviral therapy (ART) on their gut microbiota, remains under active study. Thus, our research focuses on clarifying the distinctions in intestinal microbiota composition among uninfected MSM and non-MSM healthy controls, investigating the alterations in early-stage intestinal microbial communities following HIV infection, and assessing how ART affects the intestinal microbiota. METHODS: This study enrolled four participant groups: uninfected MSM, Recent HIV-1 infection (RHI) MSM, MSM on ART, and non-MSM healthy controls, with 30 individuals in each group. We utilized 16S ribosomal DNA (16S rDNA) amplicon sequencing to analyze fecal microbiota and employed Luminex multiplex assays to measure plasma markers for microbial translocation (LBP, sCD14) and the inflammatory marker CRP. FINDINGS: Comparing uninfected MSM to non-MSM healthy controls, no substantial variances were observed in α and ß diversity. Uninfected MSM had higher average relative abundances of Bacteroidetes, Prevotella, and Alloprevotella, while Bacteroides, Firmicutes, and Faecalibacterium had lower average relative abundances. MSM on ART had lower intestinal microbiota diversity than RHI MSM and uninfected MSM. In MSM on ART, Megasphaera and Fusobacterium increased, while Faecalibacterium and Roseburia decreased at genus level. Additionally, treatment with a non-nucleoside reverse transcriptase inhibitor (NNRTI) led to significant alterations in intestinal microbiota diversity and composition compared to RHI MSM. The random forest model showed that HIV infection biomarkers effectively distinguished between newly diagnosed HIV-infected MSM and HIV-negative MSM, with an ROC AUC of 76.24% (95% CI: 61.17-91.31%). CONCLUSIONS: MSM showed early intestinal microbiota imbalances after new HIV infection. MSM on ART experienced worsened dysbiosis, indicating a combined effect of HIV and ART. NNRTI-based treatment notably changed intestinal microbiota, suggesting a potential direct impact of NNRTI drugs on intestinal microbiota.

Effects of alcohol on the composition and metabolism of the intestinal microbiota among people with HIV: A cross-sectional study.

OBJECTIVES: Alcohol consumption is not uncommon among people with HIV (PWH) and may exacerbate HIV-induced intestinal damage, and further lead to dysbiosis and increased intestinal permeability. This study aimed to determine the changes in the fecal microbiota and its association with alcohol consumption in HIV-infected patients. METHODS: A cross-sectional survey was conducted between November 2021 and May 2022, and 93 participants were recruited. To investigate the alterations of alcohol misuse on fecal microbiology in HIV-infected individuals, we performed 16s rDNA gene sequencing on fecal samples from the low-to-moderate drinking (n = 21) and non-drinking (n = 72) groups. RESULTS: Comparison between groups using alpha and beta diversity showed that the diversity of stool microbiota in the low-to-moderate drinking group did not differ from that of the non-drinking group (all p > 0.05). The Linear discriminant Analysis effect size (LEfSe) algorithm was used to determine the bacterial taxa associated with alcohol consumption, and the results showed altered fecal bacterial composition in HIV-infected patients who consumed alcohol; Coprobacillus, Pseudobutyrivibrio, and Peptostreptococcaceae were enriched, and Pasteurellaceae and Xanthomonadaceae were depleted. In addition, by using the Kyoto Encyclopedia of Genes and Genomes (KEGG), functional microbiome features were also found to be altered in the low-to-moderate drinking group compared to the control group, showing a reduction in metabolic pathways (p = 0.036) and cardiovascular disease pathways (p = 0.006). CONCLUSION: Low-to-moderate drinking will change the composition, metabolism, and cardiovascular disease pathways of the gut microbiota of HIV-infected patients.

The prevalence and factors of willingness to accept circumcision among MSM in Maanshan City, China.

To investigate the prevalence of male circumcision and the willingness to undergo male circumcision and influencing factors among MSM in Maanshan City, we conducted a cross-sectional study from June 2016 to December 2019. Respondent-driven sampling (RDS) was used to recruit participants. Influential factors of willingness to accept circumcision were identified by a multivariable logistic regression model. The multivariable logistic regression model revealed that five variables were independent influential factors for willingness to participate. The factors include that used condoms during last anal intercourse (OR = 1.87, 95% CI:1.03-3.41, P = 0.04), sex with female sex partners (OR = 0.499, 95% CI:0.298-0.860, P = 0.012, level of education (junior college: OR = 0.413, 95% CI:0.200-0.854, P = 0.017; bachelor's degree or higher: OR = 0.442, 95% CI:0.208-0.938, P = 0.033), condom use during oral sex in the last six months (OR = 4.20, 95% CI:1.47-12.0, P = 0.007) and level of knowledge of PrEP (OR = 5.09, 95% CI:1.39-18.7, P = 0.014). Given the willingness of MSM to accept circumcision was low in China, establishing a proper understanding of circumcision is essential if it is to be used as a strategy to prevent HIV infection among MSM. Therefore, publicity and education on the operation should be strengthened to increase the willingness to undergo male circumcision.

Revisiting the intersection of microglial activation and neuroinflammation in Alzheimer's disease from the perspective of ferroptosis.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by chronic neuroinflammation with amyloid beta-protein deposition and hyperphosphorylated tau protein. The typical clinical manifestation of AD is progressive memory impairment, and AD is considered a multifactorial disease with various etiologies (genetic factors, aging, lifestyle, etc.) and complicated pathophysiological processes. Previous research identified that neuroinflammation and typical microglial activation are significant mechanisms underlying AD, resulting in dysfunction of the nervous system and progression of the disease. Ferroptosis is a novel modality involved in this process. As an iron-dependent form of cell death, ferroptosis, characterized by iron accumulation, lipid peroxidation, and irreversible plasma membrane disruption, promotes AD by accelerating neuronal dysfunction and abnormal microglial activation. In this case, disturbances in brain iron homeostasis and neuronal ferroptosis aggravate neuroinflammation and lead to the abnormal activation of microglia. Abnormally activated microglia release various pro-inflammatory factors that aggravate the dysregulation of iron homeostasis and neuroinflammation, forming a vicious cycle. In this review, we first introduce ferroptosis, microglia, AD, and their relationship. Second, we discuss the nonnegligible role of ferroptosis in the abnormal microglial activation involved in the chronic neuroinflammation of AD to provide new ideas for the identification of potential therapeutic targets for AD.

Schisandrin B Alleviates Diabetic Cardiac Autonomic neuropathy Induced by P2X7 Receptor in Superior Cervical Ganglion via NLRP3.

Diabetic cardiovascular autonomic neuropathy (DCAN) is a common complication of diabetes mellitus which brings about high mortality, high morbidity, and large economic burden to the society. Compensatory tachycardia after myocardial ischemia caused by DCAN can increase myocardial injury and result in more damage to the cardiac function. The inflammation induced by hyperglycemia can increase P2X7 receptor expression in the superior cervical ganglion (SCG), resulting in nerve damage. It is proved that inhibiting the expression of P2X7 receptor at the superior cervical ganglion can ameliorate the nociceptive signaling dysregulation induced by DCAN. However, the effective drug used for decreasing P2X7 receptor expression has not been found. Schisandrin B is a traditional Chinese medicine, which has anti-inflammatory and antioxidant effects. Whether Schisandrin B can decrease the expression of P2X7 receptor in diabetic rats to protect the cardiovascular system was investigated in this study. After diabetic model rats were made, Schisandrin B and shRNA of P2X7 receptor were given to different groups to verify the impact of Schisandrin B on the expression of P2X7 receptor. Pathological blood pressure, heart rate, heart rate variability, and sympathetic nerve discharge were ameliorated after administration of Schisandrin B. Moreover, the upregulated protein level of P2X7 receptor, NLRP3 inflammasomes, and interleukin-1ß in diabetic rats were decreased after treatment, which indicates that Schisandrin B can alleviate the chronic inflammation caused by diabetes and decrease the expression levels of P2X7 via NLRP3. These findings suggest that Schisandrin B can be a potential therapeutical agent for DCAN.

Enhanced dielectric properties of polystyrene by using graphene incorporated styrene-butyl acrylate microspheres.

In view of the current trend of capacitor materials, the development of capacitors with high dielectric permittivity and low dielectric loss is of great interest. In this work, the dielectric permittivity of reduced graphene oxide-incorporated styrene-butyl acrylate (rGO@SBA) composite microspheres synthesized by mini-emulsion polymerization was significantly improved. rGO with 2 wt% content gave a dielectric permittivity of 11 356 (at 1 KHz), which was 1925 times higher than that of pure SBA (5.9). SEM and TEM were conducted to observe the morphology and structure of the composite microspheres. After filling into polystyrene (PS), a segregated structure of (rGO@SBA) that enables a concentrated aggregation of rGO in SBA was fabricated. The dielectric permittivity of PS could reach 10.91 (at 1 KHz) by incorporating only 0.39 wt% rGO by using this segregated structure of (rGO@SBA). PS simply mixed with SBA microspheres and graphite (PS/rGO-SBA) was also fabricated as a comparison group to verify the effect of this segregated structure on the dielectric properties of the composites. After comparing the dielectric properties of PS composites with different structures, the enhancement in dielectric permittivity of the composites can be demonstrated.

LncRNA-UC.25 + shRNA Alleviates P2Y14 Receptor-Mediated Diabetic Neuropathic Pain via STAT1.

Diabetic neuropathic pain (DNP) is a common complication of diabetes, and its complicated pathogenesis, as well as clinical manifestations, has brought great trouble to clinical treatment. The spinal cord is an important part of regulating the occurrence and development of DNP. Spinal microglia can regulate the activity of spinal cord neurons and have a regulatory effect on chronic pain. P2Y12 receptor is involved in DNP. P2Y14 and P2Y12 receptors belong to the Gi subtype of P2Y receptors, but there is no report that the P2Y14 receptor is involved in DNP. Closely related to many human diseases, the dysregulation of long noncoding RNA (lncRNA) has the effect of promoting or inhibiting the occurrence and development of diseases. The aim of this research is to investigate the function of the spinal cord P2Y14 receptor in type 2 DNP and to understand the function as well as the possible mechanism of lncRNA-UC.25 + (UC.25 +) in rat spinal cord P2Y14 receptor-mediated DNP. Our results showed that P2Y14 shRNA can reduce the expression of P2Y14 in DNP rats, thereby restraining the activation of microglia, decreasing the expression of inflammatory factors and the level of p38 mitogen-activated protein kinase (p38 MAPK) phosphorylation. At the same time, UC.25 + shRNA can downregulate the expression of the P2Y14 receptor, reduce the release of inflammatory factors, and diminish the p38 MAPK phosphorylation, indicating that UC.25 + can alleviate spinal cord P2Y14 receptor-mediated DNP. The RNA immunoprecipitation result showed that UC.25 + enriched signal transducers and activators of transcription1 (STAT1) and positively regulated its expression. The chromatin immunoprecipitation result indicated that STAT1 combined with the promoter region of the P2Y14 receptor and positively regulated the expression of the P2Y14 receptor. Therefore, we infer that UC.25 + may alleviate DNP in rats by regulating the expression of the P2Y14 receptor in spinal microglia via STAT1.

Naringin Relieves Diabetic Cardiac Autonomic Neuropathy Mediated by P2Y14 Receptor in Superior Cervical Ganglion.

Diabetes mellitus (DM), an emerging chronic epidemic, contributes to mortality and morbidity around the world. Diabetic cardiac autonomic neuropathy (DCAN) is one of the most common complications associated with DM. Previous studies have shown that satellite glial cells (SGCs) in the superior cervical ganglia (SCG) play an indispensable role in DCAN progression. In addition, it has been shown that purinergic neurotransmitters, as well as metabotropic GPCRs, are involved in the pathophysiological process of DCAN. Furthermore, one traditional Chinese medicine, naringin may potently alleviate the effects of DCAN. Ferroptosis may be involved in DCAN progression. However, the role of naringin in DCAN as well as its detailed mechanism requires further investigation. In this research, we attempted to identify the effect and relevant mechanism of naringin in DCAN mitigation. We observed that compared with those of normal subjects, there were significantly elevated expression levels of P2Y14 and IL-1ß in diabetic rats, both of which were remarkably diminished by treatment with either P2Y14 shRNA or naringin. In addition, abnormalities in blood pressure (BP), heart rate (HR), heart rate variability (HRV), sympathetic nerve discharge (SND), and cardiac structure in the diabetic model can also be partially returned to normal through the use of those treatments. Furthermore, a reduced expression of NRF2 and GPX4, as well as an elevated level of ROS, were detected in diabetic cases, which can also be improved with those treatments. Our results showed that naringin can effectively relieve DCAN mediated by the P2Y14 receptor of SGCs in the SCG. Moreover, the NRF2/GPX4 pathway involved in ferroptosis may become one of the principal mechanisms participating in DCAN progression, which can be modulated by P2Y14-targeted naringin and thus relieve DCAN. Hopefully, our research can supply one novel therapeutic target and provide a brilliant perspective for the treatment of DCAN.