Clinical Characteristics and Outcomes of Chronic Kidney Disease in People Living with HIV in a Resource-Limited Center of Central China.

Clinical management and optimal treatment are essential to improving outcomes for people living with HIV (PLWH). We assessed trends and outcomes of chronic kidney disease (CKD) in PLWH in a resource-limited center of central China. All PLWH who were followed up in a tertiary referral center in Wuhan, China, from July 2016 to June 2021 were evaluated. CKD was defined as glomerular filtration rate (GFR) <60 mL/min/1.73 m2 during two consecutive measurements 3 months apart. Baseline characteristics of the participants were extracted from the hospital medical records. The prevalence rate and associated risk factors of CKD were analyzed. A total of 863 PLWH with normal kidney function at baseline were analyzed. The median age was 33 (interquartile ranges: 26-49) years, and 778 (90.2%) were male and 85 (9.8%) were female. Among them, 50 (5.8%) had their GFR falling below 60 mL/min/1.73 m2 after a median of 54 months. Adjusted multivariate logistic regression revealed older age [adjusted odds ratio (aOR) = 1.04, 95% confidence interval (95% CI): 1.01-1.07], female sex (aOR = 3.17, 95% CI: 1.14-8.84), lower body weight (aOR = 0.95, 95% CI: 0.91-1.00), lower hemoglobin (aOR = 3.54, 95% CI: 1.51-8.30), longer duration of antiretroviral therapy exposure (aOR = 1.02, 95% CI: 1.00-1.04), and a baseline GFR between 60 and 90 mL/min/1.73 m2 (aOR = 3.89, 95% CI: 1.21-12.46) were associated with the development of CKD. Our findings showed that CKD is not infrequent in PLWH with a combination of traditional and HIV-specific risk factors for kidney disease, highlighting the suboptimal monitoring and treatment options of CKD in PLWH in resource-limited settings. Scalable monitoring strategy to improve care for this population is warranted.

Clinical characteristics of four cancer patients with SARS-CoV-2 infection in Wuhan, China.

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) led to the outbreak of pneumonia in Wuhan. The virus is highly infectious. Patients with cancer might be susceptible to the viral infection because of the immunosuppressive state cause by therapies on tumors. CASE PRESENTATION: We present the clinical features of four cancer patients who were infected with SARS-CoV-2 in late January of 2020 in our hospital. Cases 1 and 3 were diagnosed as mild and common type of coronavirus disease 2019 (COVID-2019) and survived from the viral infection. They acquired SARS-CoV-2 infection during their staying in hospital under radiotherapy and surgery of the tumors. Cases 2 and 4 suffered from severe type of COVID-19, and Case 2 was dead owning to the advanced age, uncontrolled chronic B cell lymphocytic leukemia and many other underlying diseases. The immunosuppressive state induced by liver transplantation and anti-rejection therapy might contribute to the severity of COVID-19 in Case 4, who suffered from hepatitis B related hepatocellular carcinoma. However, Case 4 was recovered from COVID-19 after a combination therapy against virus, bacteria and fungi, and also respiratory support. Nearly all patients showed a decrease in lymphocytes including total CD3+ T cells, B cells, and natural killer cells after infection of the virus. CONCLUSIONS: The severity of COVID-19 might be influenced by immune system state and underlying diseases in cancer patients. And the treatment of SARS-CoV-2 infection in cancer patients is challenged by the immunosuppressive state of these patients under chemotherapy or surgery.

Hepatitis B Virus Stimulated Fibronectin Facilitates Viral Maintenance and Replication through Two Distinct Mechanisms.

Fibronectin (FN) is a high molecular weight extracellular matrix protein that functions in cell adhesion, growth, migration, and embryonic development. However, little is known about the role of FN during viral infection. In the present study, we found significantly higher levels of FN in sera, and liver tissues from hepatitis B virus (HBV) patients relative to healthy individuals. HBV expression enhanced FN mRNA and protein levels in the hepatic cell lines Huh7 and HepG2. HBV infection of susceptible HepG2-sodium taurocholate co-transporting polypeptide cells also increased FN expression. We also found that transcriptional factor specificity protein 1 was involved in the induction of FN by HBV. Knockdown of FN expression significantly inhibited HBV DNA replication and protein synthesis through activating endogenous IFN-α production. In addition, FN interacted with the transforming growth factor ß-activated protein kinase 1 (TAK1) and TAK1-binding protein complex and attenuated interferon signaling by inhibiting TAK1 phosphorylation. Furthermore, the nuclear translocation of NF-κB/p65 was found to be inhibited by FN. We also observed that FN promoted HBV enhancers to support HBV expression. These results suggest novel functions of endogenous FN involved in immune evasion and maintenance of HBV replication.

Protective effects of isorhamnetin on apoptosis and inflammation in TNF-α-induced HUVECs injury.

Little is known about the role of isorhamnetin on endothelial cell apoptosis and inflammation when insulted by TNF-α injury. In our study, HUVECs were treated with TNF-α for 6 hours. HUVECs apoptosis were detected using flow cytometry. The expressions of ICAM-1, VCAM-1, E-selectin, NF-κB, AP-1 and eNOS were determined with western blotting or flow cytometry. The results showed TNF-α increased of apoptosis and the expression of ICAM-1, VCAM-1 and E-selectin in HUVECs, accompanied by significant augmentation of NF-κB and AP-1 expression. Pretreatment with isorhamnetin significantly reduced apoptosis in TNF-α-treated HUVECs. Moreover, isorhamnetin significantly attenuated TNF-α-induced upregulation of ICAM-1, VCAM-1, AP-1, E-selectin and NF-κB expression. Meanwhile, isorhamnetin also increased the expression of eNOS. So, isorhamnetin could suppress TNF-α-induced apoptosis and inflammation by blocking NF-κB and AP-1 signaling in HUVECs, which might be one of the underlying mechanisms for treatment of coronary heart disease.

Apoptosis of bone marrow mesenchymal stem cells caused by hypoxia/reoxygenation via multiple pathways.

The irreversible loss of cardiomyocytes remains a key problem to resolve, which forms the cellular basis of cardiac dysfunction. MSCs transplantation brings out a promising potential for myocardial renovation with less limitations. However, this cell transplantation therapy is limited by its poor viability after transplantation. Apoptosis is thought to be the major factor that affects the efficiency of MSCs transplantation. Therefore, exploring the process of apoptosis and the underlying mechanisms of MSCs in the 'harmful' microenvironment is significant for the sake of improving the efficiency of MSCs transplantation therapy. A hypoxia/reoxygenation (H/R) model of MSCs had been established. TUNEL, Hoechst staining and MTT were used for the evaluation of morphological changes, cell viability and apoptosis. Mitochondrial transmembrane potential was detected by JC-1 using the fluorescence microscopy system. The protein expression of cytochrome c, p-ERK, p-AKT, Bcl-2, Bax, p-JNK, HIF-1α and VEGF was assessed for the analysis of protein changes using the Western blot. In our study, H/R insult lead to apoptosis and cell viability lost in a time-dependent manner in MSCs. Multiple pathways were involved in the apoptosis of MSCs, including cytochrome c released from mitochondria to cytosol, mitochondrial transmembrane potential lost. In addition, p-ERK and p-AKT were downregulated, while Bcl-2, p-JNK and VEGF were upregulated. H/R induced the apoptosis in MSCs is through multiple pathways. These multiple pathways will be helpful for understanding and explaining the process and mechanism of apoptosis in MSCs.

Short-term pretreatment with atorvastatin attenuates left ventricular dysfunction, reduces infarct size and apoptosis in acute myocardial infarction rats.

BACKGROUND: Atorvastatin showed a number of cardiovascular benefits, however, the role and underlying molecular mechanisms of short-term atorvastatin-mediated protection remain unclear. METHODS: 30 rats were randomly divided into 3 groups: sham group, acute myocardial infarction model group and atorvastatin group. The rats of acute myocardial infarction model were established by ligation of the left anterior descending of coronary arteries. Before surgery, rats in the atorvastatin group received 20 mg/kg/d atorvastatin for 7 days in atorvastatin group. After 4 hours of model established, changes in hemodynamics parameters were recorded and myocardial infarct size was achieved by Evans blue-TTC staining. Myocardium apoptosis was evaluated by TUNEL. The expression of FAS, FAS-L, Bcl-2, Bax, p-BAD, Caspase-8 and Caspase-3 in myocardium were examined by Western blot. RESULTS: In the atorvastatin group, left ventricular function was elevated and infarct size was decreased compared with the model group. Moreover, in the atorvastatin group, the cell apoptosis index was reduced in response to myocardial infarction. The expressions of Bcl-2 were increased and Bax, p-BAD, Fas, Fas-L, caspase-8 and caspase-3 in myocardium were decreased in atorvastatin group. CONCLUSIONS: Short-term atorvastatin pretreatment restored left ventricular function and limited infarct size in acute myocardial infarction, which were associated with reduction of the apoptosis in myocardium through Bcl-2 and Fas pathway.

Aortic root dilatation is associated with carotid intima-media thickness but not with carotid plaque in hypertensive men.

BACKGROUND: The role of atherosclerosis-related processes in aortic root dilatation (ARD) has not been fully determined. The present study was to assess the relationship between carotid IMT, carotid plaque, and ARD. METHODS: Hypertensive men with ARD (n = 30) were compared with hypertensive men without ARD (n = 52) and normal control subjects (n = 29). Two-dimensional echocardiography was used to measure the aortic root at the aortic annulus, the sinus of Valsalva, the sinotubular junction and the proximal part of the ascending aorta. Carotid IMT and carotid plaque were also assessed by ultrasound. RESULTS: The measured mean carotid IMT was significantly increased in patients with ARD (1.37 +/- 0.80 mm) compared to the subjects without ARD (1.06 +/- 0.54 mm) and healthy control subjects (0.84 +/- 0.44 mm) (P < 0.05). However, no significant differences of the prevalence of carotid plaque were found in the three groups (P > 0.05). Aortic diameters at all levels except for the diameter of the supra-aortic ridge were significantly related to carotid IMT when the hypertensive population was considered (P < 0.05). No significant correlation was found between carotid plaque and aortic root dimension (P > 0.05). CONCLUSION: This study shows that carotid intima-media thickening, but not carotid atherosclerotic plaque, is positively associated with ARD. Further studies to explore the underlying mechanism are awaited.

Expression of heregulin and ErbB receptors in mesenchymal stem cells.

BACKGROUND: Mesenchymal stem cells are a promising cell type for cell transplantation in myocardial infarction. Type I neuregulins-1, also known as heregulin, can promote the survival of cardiomyocytes and stimulate angiogenesis. The purpose of this study was to investigate the expression of heregulin and ErbB receptors in mesenchymal stem cells, then further detect the secretion of heregulin and the changes in expression of heregulin and ErbB receptors under conditions of serum deprivation and hypoxia. METHODS: Mesenchymal stem cells isolated from bone marrow of 180 g male Sprague-Dawley rats were cultured. Passage 3 cells were detected experimentally by regular reverse transcriptase-polymerase chain reaction (RT-PCR), quantitative real time PCR and Western blotting. RESULTS: Heregulin and ErbB receptors were expressed in mesenchymal stem cells, and all three ErbB receptors mRNA expressions were significantly down-regulated by serum deprivation and hypoxia, but serum deprivation and hypoxia significantly increased the protein expression of heregulin. Serum deprivation and hypoxia more than 12 hours could induce the secretion of heregulin. CONCLUSIONS: Mesenchymal stem cells can express all three ErbB receptors and heregulin. Serum deprivation and hypoxia decrease the mRNA expression of ErbB receptors, increase the expression of heregulin, and activate the secretion of heregulin.

Hypoxic preconditioning attenuates hypoxia/reoxygenation-induced apoptosis in mesenchymal stem cells.

AIM: Mesenchymal stem cells (MSC) are a promising candidate for cardiac replacement therapies. However, the majority of transplanted MSC are readily lost after transplantation because of poor blood supply, ischemia-reperfusion, and inflammatory factors. We aimed to study the effects of hypoxia preconditioning (HPC) on hypoxia/reoxygenation-induced apoptosis of MSC. METHODS: Three generations of MSC were divided into 6 groups, including the normal group, hypoxia-reoxygenation (H/R) group, cyclosporine A (CsA), and the HPC 10 min, 20 min, and 30 min groups. The apoptotic index, cell viability, mitochondrial membrane potential, translocation of Bcl-2 and bax, extracellular regulated kinase (ERK), Akt, hypoxia-inducible factor 1-alpha, and the vascular endothelial growth factor (VEGF) were tested after H/R treatment. RESULTS: HPC decreased the apoptotic index and increased the viability induced by H/R. Moreover, HPC markedly stabilized mitochondrial membrane potential, upregulated Bcl-2 and VEGF expressions, and increased the phosphorylation of ERK and Akt. As a positive control, CsA has the same function as HPC, except for promoting ERK and Akt phosphorylation and upregulating VEGF. CONCLUSION: HPC had a protective effect against MSC apoptosis induced by H/R via stabilizing mitochondrial membrane potential, upregulating Bcl-2 and VEGF, and promoting ERK and Akt phosphorylation. HPC has implications for the development of novel stem cell protective strategies.

Heregulin protects mesenchymal stem cells from serum deprivation and hypoxia-induced apoptosis.

Heregulin can regulate the survival of cardiomyocytes, epithelial cells, neuron, glial cells, and other cell types through binding with the ErbB receptors. The aim of this study is to investigate the effects of heregulin (HRG) on the apoptosis of Bone marrow Mesenchymal stem cells (MSCs). We used the MSCs from adult Sprague-Dawley rats and the model of serum deprivation (SD) and hypoxia-induced apoptosis. The apoptosis was detected by TUNEL method. The apoptosis of MSCs significantly increased 12 h or 18 h after SD and hypoxia, but treatment with HRG significantly decreased the apoptosis induced by SD and hypoxia. Tyrphostin AG1478 (ErbB3/4 inhibitor) or Tyrphostin AG825 (ErbB2 inhibitor) could block this effects of HRG. Akt and ERK were activated by HRG under SD and hypoxia conditions, but HRG had no effects on the activation of JNK and p38. HRG also increased the ratio of Bcl-2/Bax and decreased the activation of caspase3 induced by SD and hypoxia. These results suggested HRG could decrease the apoptosis of MSCs induced by SD and hypoxia through the activation of Akt and ERK, the increase of Bcl-2/Bax ratio and the inhibition of caspase3 activation.