Long-term insulin resistance is associated with frailty, frailty progression, and cardiovascular disease.

BACKGROUND: Insulin resistance and diabetes are associated with an increased risk of frailty, and frailty is associated with cardiovascular disease and premature mortality. We aim to investigate the impact of long-term insulin resistance trajectories on future frailty and cardiovascular risk among young adults. METHODS: In total, 3168 participants with a 30-year follow-up period. The baseline period covered the first 15 years as the exposure period. Insulin resistance was determined using the homeostasis model assessment for insulin resistance (HOMA-IR), and three trajectories (low, moderate, and high) were constructed. The subsequent 15 years constituted the event accrual period. Frailty was assessed using a deficit accumulation mode, and cardiovascular outcomes were obtained from the 15-year event accrual period. RESULTS: The mean age of all 3168 participants was 41.0 (37.0-43.0) years, with 1750 (55.2%) being women. Participants in the high level of insulin resistance trajectory had an increased prevalence of frailty (OR: 1.55, 95% CI: 1.05-2.30, P = 0.028). Although no statistically significant associations were observed after full adjustment, single-factor analysis indicated association between the moderate and high trajectories and frailty progression. Additionally, participants with high level of insulin resistance trajectory were associated with an increased risk of cardiovascular disease, coronary heart disease, and stroke. A notable correlation between HOMA-IR trajectory and cardiovascular diseases was still discernible within the subgroup where the frailty index ≥0.12 (HR: 2.12, 95% CI: 1.17-3.83, P = 0.013) (P for interaction >0.05). CONCLUSIONS: Long-term high level of insulin resistance is associated with high prevalence of frailty, and an increased risk of cardiovascular events. Emphasizing the importance of early prevention and intervention for abnormal glucose metabolism in young adults to prevent frailty and cardiovascular disease.

Corrigendum: Human IL-17 and TNF-α additively or synergistically regulate the expression of proinflammatory genes, coagulation-related genes, and tight junction genes in porcine aortic endothelial cells.

[This corrects the article DOI: 10.3389/fimmu.2022.857311.].

Human IL-17 and TNF-α Additively or Synergistically Regulate the Expression of Proinflammatory Genes, Coagulation-Related Genes, and Tight Junction Genes in Porcine Aortic Endothelial Cells.

Immune rejection is the major limitation for porcine xenograft survival in primate recipients. Proinflammatory cytokines play important roles in immune rejection and have been found to mediate the pathological effects in various clinical and experimental transplantation trials. IL-17 and TNF-α play critical pathological roles in immune disorders, such as psoriasis and rheumatoid arthritis. However, the pathological roles of human IL-17 (hIL-17) and human TNF-α (hTNF-α) in xenotransplantation remain unclear. Here we found that hIL-17 and hTNF-α additively or synergistically regulate the expression of 697 genes in porcine aortic endothelial cells (PAECs). Overall, 415 genes were found to be synergistically regulated, while 282 genes were found to be additively regulated. Among these, 315 genes were upregulated and 382 genes were downregulated in PAECs. Furthermore, we found that hIL-17 and hTNF-α additively or synergistically induced the expression of various proinflammatory cytokines and chemokines (e.g., IL1α, IL6, and CXCL8) and decreased the expression of certain anti-inflammatory genes (e.g., IL10). Moreover, hIL-17 plus hTNF-α increased the expression of IL1R1 and IL6ST, receptors for IL1 and IL6, respectively, and decreased anti-inflammatory gene receptor expression (IL10R). hIL-17 and hTNF-α synergistically or additively induced CXCL8 and CCL2 expression and consequently promoted primary human neutrophil and human leukemia monocytic cell migration, respectively. In addition, hIL-17 and hTNF-α induced pro-coagulation gene (SERPINB2 and F3) expression and decreased anti-coagulation gene (TFPI, THBS1, and THBD) expression. Additionally, hIL-17 and hTNF-α synergistically decreased occludin expression and consequently promoted human antibody-mediated complement-dependent cytotoxicity. Interestingly, hTNF-α increased swine leukocyte antigen (SLA) class I expression; however, hIL-17 decreased TNF-α-mediated SLA-I upregulation. We concluded that hIL-17 and hTNF-α likely promote the inflammatory response, coagulation cascade, and xenoantibody-mediated cell injury. Thus, blockade of hIL-17 and hTNF-α together might be beneficial for xenograft survival in recipients.

Biomedical Analytics of Four Chinese Medicinals in Treatment of Insomnia Based on Network Pharmacology.

Aim: Our aim is to recommend the appropriate Chinese medicinals in clinical treatment of insomnia, which are suanzaorén (Semen Ziziphi Spinosae), chuanxiong (Rhizoma Chuanxiong), fúlíng (Poria), and báisháo (Radix Paeoniae Alba). Method: Based on network pharmacology, the active molecules and mechanism of these four Chinese medicinals treating insomnia were sought and analyzed. The components of the four Chinese medicinals with potential activity were collected and screened. Moreover, the recollected human disease-related targets were correlated through Cytoscape 3.8.2, and the network diagram of drug component disease targets was drawn. Based on the human protein-protein interaction database, the above network diagram was imported to establish the protein-protein interaction (PPI) and composite target pathway (C-T-P) networks. After selecting important information, the pathway analysis was carried out to show the biological process, core target, and core pathway of insomnia treatment. Result: In this study, 44 active components and 81 drug-disease common targets were obtained; 307 key targets were found in the PPI network; a core cluster composed of 14 nodes and 50 functional associations was found. Conclusion: In summary, the four Chinese medicinals' effective components and main mechanism of in the treatment of insomnia may be related to their participation in the regulation of endocrine. Compared with the existing network pharmacological analysis results of SuanZaoRénTang (Sour Jujube Decoction), which is commonly used in insomnia, they have similar effects on the immune system and HPA axis, while the focus of the four Chinese medicinals is mainly on endocrine regulation, and SuanZaoRénTang (Sour Jujube Decoction) is mainly on anti-inflammatory effect.

Salivary microbiota analysis of patients with membranous nephropathy.

The oral microbiota are closely related to human health. Nonetheless, to the best of our knowledge, their relationship with membranous nephropathy (MN) remains unstudied. The saliva microbiota collected from 22 patients with MN and 15 healthy controls were analyzed by next­generation sequencing, and bioinformatics analysis of the 16S ribosomal RNA gene was subsequently carried out. The Chao1 and Shannon indices in patients with MN were higher than those in healthy controls. Analysis of similarities revealed that the oral microbiota in the patient group were significantly different from those in the healthy controls. At the genus level, the abundance of Alloprevotella, Granulicatella, Prevotella, Streptococcus and Prevotella_7 was markedly higher in patients with MN than in healthy controls. Six operational taxonomic units (OTUs; OTU5, OTU28, OTU9, OTU15, OTU33 and OTU38) were found to be markedly correlated with the clinical factors creatinine, proteinuria in 24 h, estimated glomerular filtration rate and systolic blood pressure. A total of 28 Kyoto Encyclopedia of Genes and Genomes pathways were obtained from the significant OTUs. The oral microbiota of patients with MN were investigated and it was found that OTU5, OTU28, OTU9, OTU15, OTU33 and OTU38 may be used as biomarkers. The present findings may assist in the diagnosis of patients with MN.

Assessment of Reporting Quality in Randomized Controlled Trials of Acupuncture for Primary Insomnia with CONSORT Statement and STRICTA Guidelines.

AIM: To assess the reporting quality of randomized controlled trials (RCTs) on acupuncture for primary insomnia (PI). METHODS: Seven Chinese and English databases were searched for publication reporting RCTs on acupuncture for PI from the inception of the databases to August 6, 2021. The internationally recognized Consolidated Standards of Reporting Trials (CONSORT) statement and the International Standards for Reporting Interventions in Controlled Trials of Acupuncture (STRICTA) guidelines were used to evaluate the reporting quality. The agreement between two researchers was calculated by Cohen's kappa. RESULTS: A total of 102 eligible RCTs were assessed. According to the CONSORT statement (2017), the positive reporting rates of items such as "abstract," "background," "participants," and "numbers analyzed" were above 80%. However, the positive reporting rates of items such as "sample size," "randomization implementation," "Outcomes and estimation," "Ancillary analyses," and "Registration" were below 20%. According to STRICTA guidelines, the positive reporting rates of items such as "style of acupuncture," "reasons for acupuncture treatment," "Number of needles inserted," "Needle retention time," "Treatment regimen," and "precise description of the control intervention" were above 80%. However, the positive reporting rates of items such as "setting and context of treatment" and "practitioner background" were below 20%. CONCLUSION: It is essential to advocate the endorsement of the CONSORT statement and STRICTA guidelines to improve the quality of acupuncture RCT reports.

Comparison of Efficacy between Acupuncture Therapies in Improving Sacroiliac Joint Malposition: A Systematic Review and Meta-Analysis.

AIM: To provide available quantitative evidence of efficacy and safety of acupuncture treatments for improving sacroiliac joint malposition. METHODS: Databases such as the China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (CQVIP), Wanfang Database (Wanfang), China Biology Medicine disc (CBMdisc), PubMed, Web of Science, EMBASE, and Cochrane Library were searched by computer to collect the reports on acupuncture treatment of sacroiliac joint malposition from the database creation to July 20, 2021. The selection of included studies, data extraction and coding, and bias risk assessment were conducted independently by two reviewers. RevMan5.4 software was used for meta-analysis, and the results were expressed as mean difference (MD) or standardized mean difference (SMD), with a confidence interval (CI) of 95%. RESULTS: A total of 10 randomized controlled clinical trials (RCTs) with 1019 participants were included. Their overall quality of methodology was not high, and there may be publication bias. Meta-analysis showed that the total effective rate of the treatment group was higher than that of the control group (OR = 2.74, 95% CI 2.00 to 3.74, P < 0.00001). The treatment group was better than the control group in improving VAS score (WMD = -1.56, 95% CI -2.18 to -0.94, P < 0.00001). The ODI score of the treatment group was lower than that of the control group (WMD = -6.04, 95% CI -7.05 to -5.02, P < 0.00001). With the improvement of the JOA score, the difference of iliac transverse diameter of sacroiliac joint dislocation and the index of sacroiliac joint malposition in the treatment group were better than those in the control group (P < 0.05). There was no significant heterogeneity among the studies. CONCLUSION: Acupuncture may have therapeutic advantages in improving sacroiliac joint malposition. Acupuncture and acupotomy provide a safe way to improve the related clinical symptoms and functional disorders in activity of sacroiliac joint dislocation. However, due to the low quality of the included literature, this conclusion still needs to be further verified by more high-quality and large-sample RCTs.

Genome Sequencing Technology used to Explore the 6mA Methylation Level of Silent Alpha-Thalassemia in Postmenopausal Women.

BACKGROUND: Based on whole-genome sequencing technology our aim is to explore the expression of the alpha-thalassemia trait during menopause period at the 6mA methylation site and evaluate the significance in clinical diagnosis. METHODS: In this study, we collected peripheral blood from the women in the postmenopausal period in our hospital and used the method of (ChIP-seq) immunoprecipitation assay combined with next genome sequencing technology to select the 6mA site and differentially expressed genes and KEGG pathways and thereby investigate the clinical significance of the 6mA methylation site in women with thalassemia. RESULTS: A total of 38,879 methylation sites were selected, covering a wide range of CpG island and reference sequence genes. Methylation sites are located in different regions of the gene. PKA, PIK3C, CREB1, HSP90A, ITPR1, HSPA, and SOS were significantly enriched at the 6mA radicalization site and KEGG pathways, p < 0.01. CONCLUSIONS: The 6mA methylation site of alpha-thalassemia trait in menopause was less distributed than that of healthy controls and mainly distributed in introns. Estrogen signaling pathways may affect alpha-thalassemia in menopause through the 6mA methylation of differentially expressed genes.

Hedyotis diffusa plus Scutellaria barbata Induce Bladder Cancer Cell Apoptosis by Inhibiting Akt Signaling Pathway through Downregulating miR-155 Expression.

Traditional Chinese medicine is increasingly used to treat cancer. Our clinical experiences identify Hedyotis diffusa plus Scutellaria barbata as the most common herb-pair (couplet medicinal) used for the core treatment of bladder cancer. This study aims to investigate the antitumor effect of the herb-pair in bladder cancer cells. The results show that Hedyotis diffusa plus Scutellaria barbata inhibited bladder cancer cell growth and clone formation in a dose-dependent and time-dependent manner. It also induced cell apoptosis through decreasing Akt activation and reducing the expression of antiapoptotic proteins Bcl-2 and Mcl-1. Further experiments showed that miR-155 was reduced by the herb-pair and miRNA-155 inhibitor induced cell apoptosis and suppressed Akt activation. Overexpression of miR-155 reversed herb-pair induced cell apoptosis through activating Akt pathway in both bladder cancer cell lines. The findings reveal that Hedyotis diffusa plus Scutellaria barbata reduce Akt activation through reducing miR-155 expression, resulting in cell apoptosis. It demonstrated the potential mechanism of Hedyotis diffusa plus Scutellaria barbata for the core treatment of bladder cancer.