Mutations in the NUP93, NUP107 and NUP160 genes cause steroid-resistant nephrotic syndrome in Chinese children.

BACKGROUND: The variants of nucleoporins are extremely rare in hereditary steroid-resistant nephrotic syndrome (SRNS). Most of the patients carrying such variants progress to end stage kidney disease (ESKD) in their childhood. More clinical and genetic data from these patients are needed to characterize their genotype-phenotype relationships and elucidate the role of nucleoporins in SRNS. METHODS: Four patients of SRNS carrying biallelic variants in the NUP93, NUP107 and NUP160 genes were presented. The clinical and molecular genetic characteristics of these patients were summarized, and relevant literature was reviewed. RESULTS: All four patients in this study were female and initially presented with SRNS. The median age at the onset of the disease was 5.08 years, ranging from 1 to 10.5 years. Among the four patients, three progressed to ESKD at a median age of 7 years, ranging from 1.5 to 10.5 years, while one patient reached stage 3 chronic kidney disease (CKD3). Kidney biopsies revealed focal segmental glomerulosclerosis in three patients. Biallelic variants were detected in NUP93 in one patient, NUP107 in two patients, as well as NUP160 in one patient respectively. Among these variants, five yielded single amino acid substitutions, one led to nonsense mutation causing premature termination of NUP107 translation, one caused a single nucleotide deletion resulting in frameshift and truncation of NUP107. Furthermore, one splicing donor mutation was observed in NUP160. None of these variants had been reported previously. CONCLUSION: This report indicates that biallelic variants in NUP93, NUP107 and NUP160 can cause severe early-onset SRNS, which rapidly progresses to ESKD. Moreover, these findings expand the spectrum of phenotypes and genotypes and highlight the importance of next-generation sequencing in elucidating the molecular basis of SRNS and allowing rational treatment for affected individuals.

The disulfidptosis-related signature predicts prognosis and immune features in glioma patients.

Glioma is the most common primary malignant tumor in the central nervous system. Disulfidptosis is a recently identified programmed cell death in tumor cells overexpressing SLC7A11 under glucose starvation. Clinical prognostic significance of disulfidptosis has been reported in several tumors, and in this study, we explored the correlation of disulfidptosis with clinical prognosis, immune cell infiltration, and immunotherapy response in glioma. A total of 1592 glioma patients were included in this study, including 691 glioma patients from The Cancer Genomic Atlas (TCGA), 300 patients with from the Chinese Glioma Genomic Atlas (CGGA) array, 325 patients from CGGA sequencing, and 276 patients from Gene Expression Omnibus (GEO) GSE16011. R software (V4.2.2) and several R packages were applied to develop the risk score model and correlation calculation and visualization. Three disulfidptosis-related genes, LRPPRC, RPN1, and GYS1, were screened out and applied to establish the risk score model. Low-risk patients exhibit favorable prognosis, and the disulfidptosis-related signature significantly correlated with clinicopathological properties, molecular subtypes, and immunosuppressive microenvironment of glioma patients. We developed a disulfidptosis-related risk model to predict the prognosis and immune features in glioma patients, and this risk model may be applied as an independent prognostic factor for glioma.

The Effects of Dialysis Modality and Emotional Distress on Fatigue in Patients Undergoing Dialysis.

INTRODUCTION: Fatigue is a common but often overlooked symptom in dialysis patients. Factors affecting fatigue in dialysis patients are currently unclear. There are few studies on the effects of mental factors and dialysis modality on fatigue. This study aims to explore the potential relationship between fatigue and insomnia, as well as psychiatric disorders such as anxiety and depression among patients who undergo peritoneal dialysis (PD) or hemodialysis (HD). METHODS: There were 96 HD patients and 160 PD patients at our hospital who voluntarily participated in the survey. A questionnaire survey was conducted to gather general characteristics of the patients and to evaluate fatigue, sleep quality, anxiety, and depression levels among PD and HD patients. RESULTS: The overall fatigue score was 53.83 ± 14.22 for the PD group and 57.92 ± 16.35 for the HD group. Notably, the fatigue level was lower in the PD group compared to the HD group (p < 0.05). Univariate analysis indicated that fatigue was associated with occupational status and income in the PD group, as well as educational level and income in the HD group (p < 0.05). Correlation analysis revealed that patients in both groups who were older and had higher scores for insomnia, anxiety, and depression experienced more severe fatigue. Moreover, body mass index was positively correlated with fatigue status in the PD group, while duration of dialysis showed a positive association with fatigue in the HD group. Multivariate regression analysis identified income and depression as major factors influencing fatigue in the PD group, and duration of dialysis, income, and depression in the HD group. CONCLUSION: Patients who undergo dialysis exhibit high levels of fatigue, with the severity of fatigue being less pronounced in the PD group compared to the HD group. Fatigue in these patients is associated with the duration of dialysis, income level, and presence of depression.

Effects of haloxyfop-p-methyl on the developmental toxicity, neurotoxicity, and immunotoxicity in zebrafish.

Pesticides are extensively used in agricultural production, and their residues in soil, water, and agricultural products have become a threat to aquatic ecosystem. In this study, the toxicity of haloxyfop-p-methyl, an aryloxyphenoxypropionate herbicide was studied using the model animal zebrafish. The development of zebrafish larvae was affected by haloxyfop-p-methyl including spinal deformities, decreased body length, slow heart rate, and large yolk sac area. Behavior analysis revealed that behavior activity of larvae was weakened significantly including shortened displacement distance, reduced swimming speed, increased angular speed winding degrees, in accordance with higher AChE activity. Besides, exposure to haloxyfop-p-methyl could induce oxidative stress companied by the increased intents of ROS, MDA and increased activities of CAT and SOD. In immunotoxicity, haloxyfop-p-methyl not only reduced the innate immune cells such as neutrophils and macrophages, but also affected T cells mature in thymus. Furthermore, haloxyfop-p-methyl could induce neutrophils apoptosis, accompanied with the upregulation of the expression of proapoptotic protein such as Bax and P53 and the downregulation of the expression of antiapoptotic protein Bcl-2. In addition, haloxyfop-p-methyl could induce the expression of Jak, STAT and proinflammatory cytokine genes (IFN-γ, TNF-α, and IL-8). These results indicate that haloxyfop-p-methyl induces developmental toxicity, neurotoxicity, and immunotoxicity in zebrafish, providing a perspective on the toxicological mechanism of haloxyfop-p-methyl in teleosts.

Deep Blue Phosphorescence from Platinum Complexes Featuring Cyclometalated N-Pyridyl Carbazole Ligands with Monocarborane Clusters (CB11H12-).

The utilization of deep blue phosphorescent materials in high-performance displays and solid-state lighting requires high quantum efficiencies and color purities. Here, we describe the preparation and luminescent properties of novel platinum triplet emitters featuring cyclometalated N-pyridyl-carbazole ligands functionalized with closo-monocarborane clusters [CB11H12]-. All reported complexes were fully characterized by using standard small molecule techniques (UV-vis, cyclic voltammetry, nuclear magnetic resonance (NMR), high-resolution mass spectrometry (HRMS)), and their solid-state structures were elucidated by X-ray diffraction. These platinum phosphors emit in the blue region of the visible wavelength spectrum in both the solid and solution states. Complex 4a exhibits the highest luminous efficiency at λem = 439 nm with a photoluminescent quantum yield (PLQY) of 60% by dispersing in a PMMA matrix. Electrochemical and computational studies of complexes 4a and 4b revealed that the blue phosphorescence originates mainly from intraligand 3π → π* (3ILCT) transitions with relatively small 3MLCT mixing. A deep-blue OLED containing 4a as the light-emitting dopant was successfully fabricated using a solution-processed method, and the device exhibited blue photoluminescence with CIE coordinates of (0.17, 0.15) and a maximum external quantum efficiency (EQEmax) value of 6.2%. This article represents the pioneering study of a deep blue PhOLED using a Pt complex bearing a closo-monocarborane anion substituent, providing a new avenue into the preparation of novel triplet emitters based on boron-rich cluster anions.

Job satisfaction and its related factors among emergency department physicians in China.

Background: Job satisfaction is recognized as an important factor affecting the performance and quality of medical services of emergency department physicians. However, little is known about the status of job satisfaction among emergency department physicians in China. This study aimed to explore the current level of job satisfaction and its associated factors among emergency department physicians in China. Methods: A nationwide cross-sectional survey was conducted in China from July to August 2018. A total of 10,457 emergency department physicians completed the questionnaire. The structured online questionnaire collected information on socio-demographic characteristics, work-related factors, work-family conflict, and job satisfaction. Student's t-test or ANOVA were used to compare the job satisfaction scores in different characters. The generalized linear model was used to investigate the related factors of job satisfaction among emergency department physicians. Results: The respondents' job satisfaction average score was 12.2 ± 3.6, of which 42.01% were satisfied of which the job. The results showed that emergency department physicians over 41 years old, with a higher income and working in central and western regions were positively associated with job satisfaction. In contrast, bachelor degree and above, fixed posts, long years of service, a high frequency of night shift, perceived shortage of physicians, perceived medical errors, and higher work-family conflict scores were negatively correlated with job satisfaction among emergency department physicians. Conclusion: Job satisfaction of emergency department physicians in China is low. It is suggested that hospital administrators could improve the job satisfaction of emergency department physicians by establishing an acceptable shift system, ensuring adequate emergency department staffing, increasing their income appropriately and alleviating work-family conflict.

Ultrasound-Guided Modified Seldinger Placement of Tenckhoff Catheters in Pediatric Patients Undergoing Peritoneal Dialysis: Single Center Experience.

Minimally invasive peritoneal dialysis (PD) catheterization is increasingly common, and percutaneous PD catheters may be placed using a trocar or the Seldinger technique. There are few reports of pediatric percutaneous PD catheter insertion. We retrospectively compared the outcomes from percutaneous placement of Tenckhoff catheters using a modified Seldinger technique with catheter placement by open surgery. This single-center retrospective study compared 14 pediatric patients who received percutaneous PD catheter insertion using an ultrasound-guided modified Seldinger technique (August 2018-February 2021) with 10 patients who received open-surgical PD catheter insertion (2015-2018). Complications and catheter survival were evaluated. The overall technical success rate was 100%, but the Seldinger technique required less time (30 vs. 45 min) and smaller incisions (1.1 vs. 4.4 cm). The early complications in the Seldinger and control groups were bleeding (1 vs. 0), catheter dysfunction (1 vs. 1), abdominal pain (3 vs. 7), and exit leakage (0 vs. 1). In the Seldinger group, the median time from insertion to first use was 3 days, and the minimum follow-up was 6 months. Catheter survival at 6 months was 93% (Seldinger group) and 90% (open surgery group). The adoption of this technique at our institution led to a significant increase in the percentage of new pediatric dialysis patients commencing PD rather than hemodialysis. Collectively, the modified Seldinger technique described here was safe and feasible in pediatric patients. This approach is simpler and more rapid than open surgery, and reduces early complications and increases PD uptake.

The Relationship Between Occupational Stress and Turnover Intention Among Emergency Physicians: A Mediation Analysis.

Background: There is evidence that occupational stress is a risk factor for turnover intentions. However, the structural relationship between occupational stress and turnover intention among emergency physicians has rarely been studied. This study aimed to examine the pathways of occupational stress on turnover intention through job satisfaction and depressive symptoms among emergency physicians in China. Methods: A cross-sectional study was conducted in China from July 2018 to August 2018. Data were collected using a structured questionnaire that included demographic characteristics, occupational stress, job satisfaction, depressive symptoms, and turnover intention. Hierarchical linear regression was performed to explore the related factors of turnover intention. Structural equation modeling was used to examine the pathways from occupational stress to turnover intention. Results: A total of 10,457 emergency physicians completed the questionnaire. The score of turnover intention was 11.34 (SD = 3.25), and the average item score of turnover intention was 2.84 (SD = 0.81). In structural equation modeling, the occupational stress not only had a direct effect on turnover intention (standardized direct effect = 0.311, bias-corrected 95% confidence interval [0.261, 0.361], P < 0.001), but also had an indirect effect through job satisfaction and depressive symptoms (standardized indirect effect = 0.448, bias-corrected 95% confidence interval [0.412, 0.484], P < 0.001). However, the effect of depressive symptoms on turnover intention was weak (standardized coefficient [ß] = 0.08, P < 0.001). Conclusions: Job satisfaction partially mediated the relationship between occupational stress and turnover intention. However, due to the weak effect of depressive symptoms on turnover intention, the mediating role of depressive symptoms between occupational and turnover intention had little practical value. It is recommended that hospital administrators prioritize increasing job satisfaction of emergency physicians to reduce the impact of occupational stress on their turnover intention.

Clinical and Renal Histology Findings and Different Responses to Induction Treatment Affecting the Long-Term Renal Outcomes of Children With ANCA-Associated Vasculitis: a Single-Center Cohort Analysis.

Introduction: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is relatively rare in children. This article aimed to analyze clinical and renal histology findings and different responses to induction treatment associated with the long-term renal outcomes in children with AAV in a single center. Methods: All pediatric patients with AAV admitted to Tongji Hospital from January 2002 to January 2021 were included in the study. The demographic, clinical, pathological, laboratory, and treatment data and outcomes were collected and analyzed to identify predictors associated with response to induction treatment and progression to end-stage renal disease (ESRD). Results: In total, 48 children with AAV were included in this cohort; 81.25% of them were women, and 91.7% were microscopic polyangiitis (MPA). Kidney involvement was found in 45 patients (93.75%). The most common histopathological subtype was crescentic form in this cohort according to Berden's classification. In total, 34 patients (70.8%) showed eGFR <60 ml/min/1.73 m2 at the time of diagnosis. Complete and partial remission was achieved in 8 patients (16.7%) and 19 patients (39.6%), respectively, following 6-month induction treatment. Half of the patients eventually progressed to ESRD at a mean time of (13.04 ± 15.83) months after diagnosis. The independent predictors of nonremission following induction treatment and progression to ESRD were baseline eGFR <60 ml/min/1.73 m2 and hypertension at diagnosis. Renal survival significantly decreased over time in patients with renal sclerotic subtypes or those with nonremission following induction treatment by Kaplan-Meier curve estimation. Conclusions: Our study demonstrates that women, MPA, and crescentic subtypes are predominant in pediatric AAV in China. Initial renal failure (eGFR <60 ml/min/1.73 m2), hypertension, sclerotic pathological subtype, and nonremission following induction treatment are predictive of long-term renal outcomes.

Effects of chlorobromoisocyanuric acid on embryonic development and immunotoxicity of zebrafish.

Although chlorobromoisocyanuric acid has been widely used in agriculture, its deleterious toxicity on aquatic organisms remains rare. In this study, zebrafish were exposed to chlorobromoisocyanuric acid (0, 30, 40, and 50 mg/L) from 10 to 96 h post-fertilization (hpf). We found a significant reduction in immune cell numbers (neutrophils and macrophages) and the area of thymus at 96 hpf. The expression of immune-related genes and pro-inflammatory cytokines genes were upregulated. Besides, chlorobromoisocyanuric acid triggered neutrophils cell apoptosis. The mRNA and protein levels of pro-apoptotic p53 pathway and the Bax/Bcl-2 ratio further indicated the underlying mechanism. Furthermore, the oxidative stress was observed that the accumulation of reactive oxygen species and malondialdehyde significantly increased. Subsequently, the antioxidant agent astaxanthin significantly attenuated the level of oxidative stress and the dysregulation of inflammatory response. In summary, our results showed that chlorobromoisocyanuric acid induced developmental defects and immunotoxicity of zebrafish, partly owing to oxidative stress and cell apoptosis.

Prevalence of self-medication with antibiotics and its related factors among Chinese residents: a cross-sectional study.

BACKGROUND: Self-medication is one of the most common forms of inappropriate use of antibiotics. This study aimed to assess the prevalence of self-medication with antibiotics (SMA) in China and evaluate the related factors. METHODS: A cross-sectional survey was conducted in Wuhan, Hubei, China from July 1, 2019 to July 31, 2019. Participants were recruited in public places to answer a structured questionnaire. The information of participants' social demographic characteristics, antibiotic knowledge and health beliefs were collected. Binary Logistics regression analysis was used to examine the associated factors of SMA. RESULTS: Of the 3206 participants, 10.32% reported SMA in the past 6 months. Participants who with middle or high perceived barriers to seek health care services showed a higher likelihood of SMA (P < 0.05). Participants who with middle or high perceived threats of self-medication, and who with middle or high self-efficacy to overcome obstacles showed a lower likelihood of SMA (P < 0.05). CONCLUSIONS: Compared with developed countries, the prevalence of SMA in China is still higher. Measures to conduct public health education and improve the accessibility of health services are crucial to decrease the overall self-medication rate in China.

Prevalence of antibiotic self-medication behavior and related factors among children aged 0 to 5 years.

Background: Self-medication behavior has great adverse effects on children. The aims of this study were to assess the prevalence of self-medication with antibiotics (SMA) among children aged 0-5 years and explore the related factors.Methods: A cross-sectional survey was conducted from 1 July 2019 to 31 July 2019 in Wuhan, Hubei Province (Central China). A structured questionnaire was used to collect data from 1188 parents of children aged 0-5 years on sociodemographic characteristics, SMA among children, antibiotic knowledge and health beliefs of SMA.Results: Of the 1188 participants, 14.32% had self-medicated their children with antibiotics in the past 6 months. The higher the degree of perceived threat (OR = 0.94, 95%CI: 0.89-1.00) and self-efficacy (OR = 0.94, 95%CI: 0.89-0.98), the less likely parents were to self-medicate their children. On the contrary, the higher the degree of perceived barriers, the more likely parents were to self-medicate their children with antibiotics (OR = 1.058, 95%CI: 1.01-1.11).Conclusions: Health beliefs of parents were significantly associated with SMA among children. In addition to extensive health education, the Chinese government should also improve the accessibility and quality of health services to reduce the barriers of parental behavior change.

The application of neutrophil gelatin-related lipid delivery protein in evaluation of renal function, nutrition, anemia and inflammation in patients with CKD.

OBJECTIVE: To investigate the role of neutrophil gelatinase-associated lipocalin in the evaluation of renal function, nutrition, anemia and inflammation in patients with chronic kidney diseases. MATERIALS AND METHODS: A total of 302 patients with chronic kidney diseases were selected, and their clinical data, blood neutrophil gelatinase-associated lipocalin levels, renal function, nutrition, anemia, inflammation and calcium, and phosphorus metabolism were analyzed. RESULT: Serum neutrophil gelatinase-associated lipocalin level increased with the progression of chronic kidney diseases. Higher neutrophil gelatinase-associated lipocalin levels were observed in patients with chronic kidney diseases stage 3b compared with healthy individuals (P<0.05), while the patients with chronic kidney diseases stage 5 showed higher levels compared with other chronic kidney diseases stages (P<0.01). Moreover, the ROC curve showed that neutrophil gelatinase-associated lipocalin had a better diagnostic performance from the chronic kidney diseases stage 3b to 5 (P<0.05). In addition, the serum neutrophil gelatinase-associated lipocalin levels in patient with chronic kidney diseases were negatively correlated with body mass index, number of red blood cells, hemoglobin, transferrin, the estimatedglomerular filtration rate (eGFR), serum calcium (P<0.01); and were positively correlated with mean arterial blood pressure, blood BUN, SCr and alpha 1 microglobulin, beta 2 microglobulin, urinary inhibition C, homocysteine, PTH levels, neutrophils ratio, free serum ferritin and c-reactive protein (P<0.01); while no significant correlation was found with gender, and age (P>0.05). CONCLUSION: Serum neutrophil gelatinase-associated lipocalin levels are closely related to renal function injury, inflammatory response and anemia-related indicators in patients with chronic kidney diseases, and thus could be used as a diagnostic biomarker for evaluating the degree of renal injury and related complications in patients with chronic kidney diseases.

Constructing Controllable Logic Circuits Based on DNAzyme Activity.

Recently, DNA molecules have been widely used to construct advanced logic devices due to their unique properties, such as a simple structure and predictable behavior. In fact, there are still many challenges in the process of building logic circuits. Among them, the scalability of the logic circuit and the elimination of the crosstalk of the cascade circuit have become the focus of research. Inspired by biological allosteric regulation, we developed a controllable molecular logic circuit strategy based on the activity of DNAzyme. The E6 DNAzyme sequence was temporarily blocked by hairpin DNA and activated under appropriate input trigger conditions. Using a substrate with ribonucleobase (rA) modification as the detection strand, a series of binary basic logic gates (YES, AND, and INHIBIT) were implemented on the computational component platform. At the same time, we demonstrate a parallel demultiplexer and two multi-level cascade circuits (YES-YES and YES-Three input AND (YES-TAND)). In addition, the leakage of the cascade process was reduced by exploring factors such as concentration and DNA structure. The proposed DNAzyme activity regulation strategy provides great potential for the expansion of logic circuits in the future.

Clinical characterization and diagnosis of cystic fibrosis through exome sequencing in Chinese infants with Bartter-syndrome-like hypokalemia alkalosis.

Cystic fibrosis (CF) is a fatal autosomal-recessive disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. CF is characterized by recurrent pulmonary infection with obstructive pulmonary disease. CF is common in the Caucasian population but is rare in the Chinese population. The symptoms of early-stage CF are often untypical and may sometimes manifest as Bartter syndrome (BS)-like hypokalemic alkalosis. Therefore, the ability of doctors to differentiate CF from BS-like hypokalemic alkalosis in Chinese infants is a great challenge in the timely and accurate diagnosis of CF. In China, sporadic CF has not been diagnosed in children younger than three years of age to date. Three infants, who were initially admitted to our hospital over the period of June 2013 to September 2014 with BS-like hypokalemic alkalosis, were diagnosed with CF through exome sequencing and sweat chloride measurement. The compound heterozygous mutations of the CFTR gene were detected in two infants, and a homozygous missense mutation was found in one infant. Among the six identified mutations, two are novel point mutations (c.1526G > C and c.3062C > T) that are possibly pathogenic. The three infants are the youngest Chinese patients to have been diagnosed with sporadic CF at a very early stage. Follow-up examination showed that all of the cases remained symptom-free after early intervention, indicating the potential benefit of very early diagnosis and timely intervention in children with CF. Our results demonstrate the necessity of distinguishing CF from BS in Chinese infants with hypokalemic alkalosis and the significant diagnostic value of powerful exome sequencing for rare genetic diseases. Furthermore, our findings expand the CFTR mutation spectrum associated with CF.

Autophagy protects podocytes from sublytic complement induced injury.

Podocyte injury induced by sublytic complement attack is the main feature of membranous nephropathy (MN). This study aimed at investigating the impact of sublytic complement attack-related autophagy on podocyte injury in vitro. Here, we show that sublytic complement attack enhances MPC5 podocyte autophagy in vitro. Inhibition of autophagy by treatment with 3-methyladenine (3-MA) significantly increased sublytic complement attack-induced changes in the injury-related morphology, stress fiber, and podocyte apoptosis, but decreased the survival and adhesion of MPC5 podocytes. In contrast, promotion of autophagy by treatment with rapamycin mitigated sublytic complement attack-induced changes in the injury-related morphology, stress fiber, and podocyte apoptosis, but increased the survival and adhesion of MPC5 podocytes. These data suggest that autophagy may protect podocytes from sublytic complement attack-induced injury in vitro.

Fenofibrate pre-treatment suppressed inflammation by activating phosphoinositide 3 kinase/protein kinase B (PI3K/Akt) signaling in renal ischemia-reperfusion injury.

The aim of this study was to investigate the possible beneficial effects of Fenofibrate on renal ischemia-reperfusion injury (IRI) in mice and its potential mechanism. IRI was induced by bilateral renal ischemia for 60 min followed by reperfusion for 24 h. Eighteen male C57BL/6 mice were randomly divided into three groups: sham-operated group (sham), IRI+saline group (IRI group), IRI+Fenofibrate (FEN) group. Normal saline or Fenofibrate (3 mg/kg) was intravenously injected 60 min before renal ischemia in IRI group and FEN group, respectively. Blood samples and renal tissues were collected at the end of reperfusion. The renal function, histopathologic changes, and the expression levels of pro-inflammatory cytokines [interleukin-8 (IL-8), tumor necrosis factor alpha (TNF-α) and IL-6] in serum and renal tissue homogenate were assessed. Moreover, the effects of Fenofibrate on activating phosphoinositide 3 kinase/protein kinase B (PI3K/Akt) signaling and peroxisome proliferator-activated receptor-α (PPAR-α) were also measured in renal IRI. The results showed that plasma levels of blood urea nitrogen and creatinine, histopathologic scores and the expression levels of TNF-α, IL-8 and IL-6 were significantly lower in FEN group than in IRI group. Moreover, Fenofibrate pretreatment could further induce PI3K/Akt signal pathway and PPAR-α activation following renal IRI. These findings indicated PPAR-α activation by Fenofibrate exerts protective effects on renal IRI in mice by suppressing inflammation via PI3K/Akt activation. Thus, Fenofibrate could be a novel therapeutic alternative in renal IRI.

HBx transfection limits proliferative capacity of podocytes through cell cycle regulation.

Our previous studies have shown that podocyte number is significantly decreased in glomeruli of children with hepatitis B virus (HBV)-associated glomerulonephritis. In this study, we aimed to explore whether exogenous expression of HBx protein could directly inhibit podocyte proliferation in vitro, and to investigate its role in cell cycle regulation. HBx gene was delivered into cultured mouse podocytes through an adenovirus-based vector. Cell morphology was evaluated with Wright-Giemsa staining. Cell growth and proliferation were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and 5,6-carboxyfluorescein diacetate, succinimidyl ester (CFSE)-based proliferation assays. Cell cycle phase was analyzed by flow cytometry, and the expression of cell cycle regulatory proteins was examined by western blot analysis. It was found that the aberrant nuclear changes like double and multiple micronuclei, which reflect mitotic catastrophe, accumulated in podocytes after 5 days post-infection. MTT assay showed that Ad.HBx-infected podocytes grew much more slowly than controls at day 4 post-infection and thereafter. Furthermore, CFSE-based proliferation assay also showed that the proliferation of HBx-expressing podocytes was significantly inhibited than that of controls at 3-day post-infection, and that the difference became much more obvious at day 5 post-infection. Cell cycle analysis showed that the transfection of HBx resulted in significant up-regulation of both cyclin B1 and CDK-inhibitor p21 expression and G2/M phase arrest, and slight down-regulation of cyclin A expression. These results demonstrated that exogenous expression of HBx might limit the proliferative capacity of podocytes through cell cycle regulation, thus suggesting that HBx may play a role in podocyte injuries in HBV-associated glomerulonephritis.