New insights into the mucosal immune pathogenesis of IgA nephropathy from the perspective of COVID-19 vaccination.

Large-scale SARS-CoV-2 vaccination is one of the key strategies to curb the COVID-19 pandemic; however, there are increasing reports of IgA nephropathy following COVID-19 vaccination. The clinical manifestation, treatment and prognostic effects are different in IgAN patients who have had an onset after the first and second dose of vaccination, as well as new and recurrent IgAN patients. These conditions bring about a relatively important window for understanding the pathogenesis of IgAN. Gd-IgA1 is the core of the pathogenesis of IgAN. Most IgA is produced at mucosal sites; however, antigen-activated Toll-like receptor activation pathways expressed by antigen-presenting cells and B-cell homing receptors are different in the intestinal and respiratory mucosa, and the link between respiratory and intestinal mucosa is not well understood in the pathogenesis of IgAN. Budesonide treatment of IgAN is thought to inhibit the intestinal immune response by binding to glucocorticoid receptors in the intestinal mucosa or submucosa; however, it is unclear whether there is a therapeutic effect in respiratory mucosa-derived IgA nephropathy. The present review firstly described the relationship between the gut and respiratory mucosa, and the differences in antigen-presenting cell activation pathways and B-cell homing from the perspective of COVID-19 vaccines.

New-onset IgA nephropathy following COVID-19 vaccination.

Coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused significant economic and health damage worldwide. Rapid vaccination is one of the key strategies to curb severe illness and death due to SARS-CoV-2 infection. Hundreds of millions of people worldwide have received various COVID-19 vaccines, including mRNA vaccines, inactivated vaccines and adenovirus-vectored vaccines, but the side effects and efficacy of most vaccines have not been extensively studied. Recently, there have been increasing reports of immunoglobulin A nephropathy (IgAN) after COVID-19 vaccination, however, whether their relationship is causal or coincidental remains to be verified. Here, we summarize the latest clinical evidence of IgAN diagnosed by renal biopsy associated with the COVID-19 vaccine published by 10 July 2022 with the largest sample size, and propose a hypothesis for the pathogenesis between them. At the same time, the new opportunity presented by COVID-19 vaccine allows us to explore the mechanism of IgAN recurrence for the first time. Indeed, we recognize that large-scale COVID-19 vaccination has enormous benefits in preventing COVID-19 morbidity and mortality. The purpose of this review is to help guide the clinical assessment and management of IgA nephropathy post-COVID-19 vaccination and to enrich the 'multi-hit' theory of IgA nephropathy.

ANCA-associated vasculitis following the CoronaVac vaccination.

With the coronavirus disease 2019 (COVID-19) pandemic, vaccination has become one of the cornerstones to contain the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Large clinical trials have shown high efficacy and safety of SARS-CoV-2 vaccination against COVID-19. However, with the widespread use of SARS-CoV-2 vaccines worldwide, an increasing number of reports describe the onset of glomerular disease. Here, we report a case of a 70-year-old Chinese woman who developed new antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis within 4 h post the first dose of CoronaVac. CoronaVac is an inactivated SARS-CoV-2 vaccine developed by Sinovac Life Sciences (Beijing, China). Her clinical symptoms were nausea, fatigue, acute kidney injury, and proteinuria. Laboratory tests showed markedly elevated serum myeloperoxidase titers, and the renal biopsy showed microcellular fibrous crescent formation. Renal function of the patient responded favorably after treatment with steroids and cyclophosphamide. Although there is no direct evidence of a link between vasculitis and vaccination, similar complications should be monitored as potential adverse events with widespread vaccination globally.

Reference values of glomerular filtration rate for healthy adults in southern China: a cross-sectional survey.

BACKGROUND: Currently the global data on the glomerular filtration rate of healthy adults are insufficient, with relatively little data for other races and countries. Especially in China, there are no such figures. METHODS: In this cross-sectional study, we included healthy Han adults in southern China. Participants completed a lifestyle and medical history questionnaire and had their blood pressure measured, and blood and urine samples collected. Serum creatinine was measured and used to estimated glomerular filtration rate (eGFR) by the Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formulae. The normal range of eGFR is described, and the influence of gender and age on eGFR is analyzed by the statistical method. RESULTS: We provided the largest sample size of eGFR research in China at present. The mean age of the 20,930 healthy individuals was 40.9 ± 12.3 years, 58.8% were women. The eGFRMDRD for women and men were 111.3 ± 17.4 mL/min per 1.73 m2 and 103.3 ± 15.9 mL/min per 1.73 m2, respectively. The eGFRCKD-EPI for women and men were 110.3 ± 12.1 mL/min per 1.73 m2 and 103.8 ± 13.3 mL/min per 1.73 m2, respectively. The eGFRMDRD of women and men in all age groups decreased continuously by 7.3 ml/min/1.73 m2/decade and 4.4 ml/min/1.73 m2/decade, respectively. The eGFRCKD-EPI of women and men in all age groups decreased continuously by 8.4 ml/min/1.73 m2/decade and 6.9 ml/min/1.73 m2/decade. CONCLUSIONS: The eGFR of women is higher than men and with the increasing age, the eGFR of women declines faster than men.

Effect of asymmetry on cooperation in spatial evolution.

Asymmetry is omnipresent in human society and nature and the reasons causing asymmetry are multiple. To think about the impact of asymmetries on the cooperation systems, we focus on a typical model of great asymmetric traits-the boxed pigs game-and extended the one-to-one interaction to the interaction in population. We consider the asymmetry of payoff and the spatial structure of the two populations in space. Our results have shown that the almost equal abundance and strength of two populations kills cooperative behavior. The single increase of either strength-asymmetry or abundance-asymmetry promotes cooperation. But high levels of both asymmetries would inhibit cooperative behavior, making the powerful mechanism of cooperation broken.

LncRNA HOXA11-AS Aggravates Keloid Progression by the Regulation of HOXA11-AS-miR-205-5p-FOXM1 Pathway.

BACKGROUND: Keloid is troublesome for patients' skin appearance and mental health, although it is a benign tumor. Long noncoding RNA (lncRNA) troubling keloid is frequently reported. The purpose of this study was to investigate the role of lncRNA homeobox (HOX) A11 antisense (HOXA11-AS) and related action mechanisms during the development of keloid. METHODS: The expression of HOXA11-AS, miR-205-5p, and forkhead box M1 (FOXM1) was measured by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation or apoptosis was assessed using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium (MTT) assay or flow cytometry assay. Cell migration and invasion were monitored by transwell assay. The protein levels of extracellular matrix (ECM) proteins (collagen I and collagen III), fibronectin, glucose transporter 1 (GLUT1), lactate dehydrogenase A (LDHA), and FOXM1 were quantified by Western blot. Glycolysis processes were investigated by the glycolysis stress test, glucose consumption, and lactate production. The relationship between miR-205-5p and HOXA11-AS or FOXM1 was predicted by the online tool MIRcode or starBase v2.0 and verified by dual-luciferase reporter assay or RNA immunoprecipitation (RIP). RESULTS: HOXA11-AS and FOXM1 were significantly upregulated in keloid tissues and keloid fibroblasts, while miR-205-5p was downregulated. HOXA11-AS knockdown or miR-205-5p enrichment inhibited proliferation, migration, invasion, ECM accumulation, and glycolysis but accelerated apoptosis of keloid fibroblasts. MiR-205-5p was targeted by HOXA11-AS, and its inhibition overturned the effects of HOXA11-AS knockdown. Moreover, FOXM1 was a target of miR-205-5p, and HOXA11-AS regulated the expression of FOXM1 by adsorbing miR-205-5p. FOXM1 overexpression abolished the role of miR-205-5p enrichment. CONCLUSIONS: The HOXA11-AS-miR-205-5p-FOXM1 pathway may be an active mode in which HOXA11-AS participates in the progression of keloid.

Up-Regulation of miR-26a-5p Inhibits E2F7 to Regulate the Progression of Renal Carcinoma Cells.

BACKGROUND: Metastasis is the main cause of renal cell carcinoma (RCC) tumor death, and effective inhibition of RCC metastasis is an essential means to meliorate the prognosis of RCC patients. MicroRNAs (miRs) have been proved to be stable and important biomarkers for several malignancies. This study is therefore set out to explore the metastasis-related miR and its mechanism in RCC. METHODS: The expression of miR- 26a -5p in RCC was analyzed using the expression profile in the Cancer Genome Atlas (TCGA). MiR-26a-5p and E2F transcription factor 7 (E2F7) in RCC patients were detected by qRT-PCR. Cell Counting Kit-8 (CCK-8) was adopted to assess cell proliferation, Transwell was utilized to evaluate migration and invasion, and flow cytometry (FC) was used to determine apoptosis. Mouse cell-derived and patient-derived xenotransplantation models were established to evaluate the effect of miR-26a-5p on tumor growth and metastasis in vivo. The molecular mechanism of miR-26a-5p was analyzed by dual-luciferase reporter (DLR) gene analysis, qRT-PCR, and Western blot (WB) both in vivo and in vitro. RESULTS: MiR-26a-5p was reduced in renal carcinoma cells and may serve as a biomarker for renal cancer metastasis and prognosis. MiR-26a-5p up-regulation inhibited migration and invasion in renal cell lines and tumor metastasis in vivo. Bioinformatics target prediction and RNA-seq results showed that E2F7 was among the targets of miR-26a-5p and was significantly inhibited by miR-26a-5p in vivo and in vitro. CONCLUSION: MiR-26a-5p presents low expression in RCC and promotes RCC cell apoptosis and prevents cells from proliferating and invading by targeting E2F7, which is a promising therapeutic target for RCC.

TEAD4 transcriptional regulates SERPINB3/4 and affect crosstalk between keratinocytes and T cells in psoriasis.

Psoriasis is a common chronic inflammatory disease with the prevalence rate of approximately 1-3 %. Currently, it is generally believed that the pathogenesis of psoriasis is a T-cell immune-mediated skin disease mediated by multiple genes and factors, and the interaction between keratinocytes and T cells. TEA domain family member 4 (TEAD4) is a transcription factor which regulates the expression of downstream genes in Hippo pathway and affects several biological processes, such as regulating cell differentiation and embryonic development. However, few studies have reported the role of TEAD4 in psoriasis and its possible regulatory mechanism. In this study, we found the expression level of TEAD4 in the skin of psoriasis was significantly higher than that of normal skin. In patients with the pathological keratinocytes, TEAD4 can transcriptionally regulate the expression of SERPINB3/4 and affect the secretion of chemokines, and the depletion of SERPINB3/4 inhibited the secretion of chemokines. In addition, the supernatant of keratinocytes of patients can significantly increase the migration ability of T cells, and the supernatant of T cells cultured by the supernatant of keratinocytes of patients can significantly enhance the proliferation ability of keratinocytes. Therefore, our results suggested that TEAD4 is a key regulatory factor in progression of psoriasis, and the crosstalk between keratinocytes and T cells mediated by TEAD4 plays a critical role in the psoriasis pathogenesis.

Serum level of advanced oxidation protein products (AOPPs) in patients with Henoch-Schonlein purpura and its relationship with aberrant glycosylation of IgA1 and Cosmc mRNA expression.

BACKGROUND: Henoch-Schonlein purpura (HSP) is a systemic small vessel vasculitis that is mainly caused by IgA1-type immune complex deposition. Advanced oxidation protein products (AOPPs) are specific markers of protein oxidation. OBJECTIVE: To explore the role of AOPPs in the pathogenesis of HSP. METHODS: There are 51 HSP patients who were divided into four subgroups: (i) skin type - 20 cases; (ii) joint type - 8 cases; (iii) abdominal type - 12 cases; (iv) renal type - 11 cases; and 18 healthy volunteers were enrolled as controls. The serum levels of AOPPs and Gd-IgA1 were quantified by an HAA-lectin-based ELISA. The Cosmc mRNA expression in peripheral B lymphocytes was measured by RT-PCR. RESULTS: 1. Advanced oxidation protein products in different subgroups of HSP patients are all higher than the controls, while the renal-type subgroup is the highest and the skin-type subgroup is the lowest. 2. Spearman correlation analysis shows that: (i) AOPPs and Gd-IgA1 in HSP patients are positively correlated; both of them are positively correlated with the disease severity scores; (ii) AOPPs are negatively correlated with the relative expression value (RQ) of Cosmc mRNA. CONCLUSION: Advanced oxidation protein products play an important role in the pathogenesis of HSP, especially in renal-type patients.

Curcumin Attenuates Airway Inflammation and Airway Remolding by Inhibiting NF-κB Signaling and COX-2 in Cigarette Smoke-Induced COPD Mice.

The purpose of this study is to evaluate the therapeutic effects of curcumin on airway inflammation using LPS and cigarette smoke (LC)-induced COPD murine models and LPS-stimulated human bronchial epithelial (BEAS-2B) cells. In this research, COPD murine models were established after challenged with LPS for 2 days and exposed to cigarette smoke for 35 days. Treatment with curcumin for 10 days distinctly alleviated airway inflammation and airway remolding in LC-induced COPD mice according to the lung H&E histopathological examination. The number of neutrophils and lymphocytes in broncho alveolar lavage fluid (BALF) was significantly decreased in curcumin+LC-treated group compared with the LC-induced mice. Additionally, curcumin inhibited BEAS-2B cells proliferation, which suggested the preventive effect of curcumin on progressive airway remolding and inflammatory response mediated by bronchial epithelial cells. Further investigation demonstrated an underlying molecular mechanism for the therapeutic effects of curcumin may rely on the inhibition of the degradation of IκBα and COX-2 expression in curcumin+LC-treated COPD mice and LPS-stimulated BEAS-2B cells. Overall, curcumin alleviates the airway inflammation and airway remolding, which is closely related to inhibit the BEAS-2B cells proliferation and suppress the activation of NF-κB and COX-2 expression. These findings indicate that curcumin may be a potential agent for the therapy of COPD.

Overexpression of oxidored-nitro domain containing protein 1 induces growth inhibition and apoptosis in human prostate cancer PC3 cells.

Previous studies have reported that oxidored-nitro domain containing protein 1 (NOR1) is a novel tumor suppressor gene identified in various types of cancer, such as nasopharyngeal carcinoma and cervical cancer. Recent studies have shown that NOR1 expression is lower in prostate cancer compared with normal prostate tissue. However, the specific function and exact mechanism of NOR1 in prostate cancer remains to be clarified. The present study aimed to investigate the function and mechanism of NOR1 in prostate cancer PC3 cells. DU145 and PC3 cells were transduced with a vector and cell viability, proliferation and apoptosis were determined. As predicted, NOR1 overexpression significantly inhibited growth and apoptosis in PC3 cells. NOR1 overexpression decreased the expression of the anti-apoptotic genes Bcl-2 and Bcl-xl and increased the level of the pro-apoptotic genes Bax and Bak in PC3 cells. Further investigation demonstrated that NOR1 overexpression activates caspase-3. Silencing of NOR1 did not inhibit growth or induce apoptosis in PC3 cells. Moreover, NOR1 inhibited proliferation and induced apoptosis via the activation of MAPK. The overexpression of NOR1 significantly inhibited tumor growth in PC3 tumor-bearing nude mice. The results suggest that the upregulated NOR1 expression was able to inhibit the progression of prostate cancer. Thus, NOR1 may be an ideal target for the treatment of prostate cancer.

Mechanisms, clinically curative effects, and antifungal activities of cinnamon oil and pogostemon oil complex against three species of Candida.

The anti-fungus mechanisms and curative effects of cinnamon oil and pogostemon oil complexes towards intestinal Candida infections were investigated. We measured the minimal inhibitory concentration (MIC) values of the complexes against Candida using proportionally-diluted test-tube medium, and examined the evolution of the morphology and structures of Candida albicans using scanning electronic microscopy (SEM) and transmission electronic microscopy (TEM). We found that the average MIC values of the complexes against the fungi were 0.064 mg/mL (cinnamon oil), 0.032 mg/mL (pogostemon oil) for Candida albicans, 0.129 mg/ mL (cinnamon oil), 0.064 mg/mL (pogostemon oil) for Candida tropicalis, and 0.129 mg/mL (cinnamon oil), 0.064 mg/mL (pogostemon oil), for Candida krusei. SEM examination over a 24-48 h period showed that the morphology of Candida albicans cells changed significantly. Irregular hollows appeared on the surfaces, inside organelles were destroyed and the cells burst after treatment. TEM examination over a 48 - 72 h period indicated that the cell walls were damaged, organelles were destroyed and most cytoplasms became empty bubbles. Sixty intestinal Candida-infected patients were treated with a capsule containing cinnamon and pogostemon oil. The curative ratio was 71.67% (43/60), and the improvement ratio was 28.33% (17/ 60), giving a total ratio of 100%. Thus, the cinnamon oil and pogostemon oil complexes had strong anti-fungus effects against Candida albicans, Candida tropicalis, and Candida krusei. They impacted the morphology and sub-micro structures of the fungus within 48 - 72 h, and eventually denatured and killed the cells. The complexes have also shown considerable curative effects to intestinal Candida infections.