Background and purposeDiabetic kidney disease (DKD) is a major microvascular complication of type 2 diabetes mellitus (T2DM). High-density lipoprotein cholesterol (HDL-C) has traditionally been considered renoprotective, yet growing evidence suggests that HDL subclasses may differ in biological function. This study aimed to investigate the association between HDL subclasses, particularly HDL2b, and chronic kidney disease (CKD) in Chinese adults with T2DM.MethodsIn this cross-sectional study, patients with T2DM were enrolled. CKD was defined as urinary albumin-to-creatinine ratio (UACR) ≥3.0 mg/mmol and/or estimated glomerular filtration rate (eGFR) ≤60 mL/min/1.73 m². HDL subclasses were measured using capillary electrophoresis-based microfluidics. Participants were categorized into quartiles of HDL-C, HDL2b, and HDL3. Multivariable logistic regression models were constructed with progressive adjustment for anthropometric indices, hypertension, insulin resistance (HOMA-IR), and inflammatory markers.ResultsAmong 481 patients with T2DM, 136 (28.3%) had CKD. Patients with CKD exhibited significantly lower HDL2b levels (P = 0.001), together with greater insulin resistance and systemic inflammation (all P<0.05). HDL2b showed stronger inverse correlations than total HDL-C with adiposity, glycemic indices, insulin resistance, and inflammatory markers (all P<0.05). In multivariable logistic regression, higher HDL2b was independently associated with a lower risk of CKD. Compared with the lowest quartile, the third and fourth quartiles were associated with reduced odds of CKD (Q3: OR = 0.425, 95% CI 0.220–0.821, P = 0.012; Q4: OR = 0.367, 95% CI 0.188–0.717, P = 0.001). The inverse association between HDL2b and CKD was stronger in participants with higher insulin resistance (P for interaction=0.044).ConclusionHigher HDL2b, but not total HDL-C or HDL3, is independently associated with lower risk of CKD in T2DM. HDL2b may serve as a sensitive biomarker for early renal risk stratification.

Lymphatic metastasis is a well-known factor for initiating distant metastasis of head and neck squamous cell carcinoma (HNSCC), which caused major death in most patients with cancer. Meanwhile, metabolic reprogramming to support metastasis is regarded as a prominent hallmark of cancers. However, how metabolic disorders drive in HNSCC remains unclear. We firstly established a new classification of HNSCC patients based on metabolism gene expression profiles from the TCGA and GEO database, and identified an enriched carbohydrate metabolism subgroup which was significantly associated with lymphatic metastasis and worse clinical outcome. Moreover, we found that highly activated pyruvate metabolism endowed tumors with EPHB2 upregulation and promoted tumor lymphangiogenesis independently of VEGF-C/VEGFR3 signaling pathway. Mechanically, high nuclear acetyl-CoA production from pyruvate metabolism promoted histone acetylation, which in turn transcriptionally upregulated EPHB2 expression and secretion in tumor cells. EPHB2 bound with EFNB1 in lymphatic endothelial cells promoted YAP/TAZ cytoplasmic retention, which alleviated YAP/TAZ-mediated prospero homeobox protein 1 (PROX1) transcriptional repression, and then triggered tumor lymphangiogenesis. Importantly, combined treatment with EFNB1-Fc and VEGFR3 inhibitor synergistic abrogated lymphangiogenesis in vitro and in vivo, suggesting that targeting EPHB2 might be a potential strategy to patients with no or slight response to VEGFR3 inhibitor. These findings uncover the mechanism by which pyruvate metabolism is linked to lymphatic metastasis of tumor and provides a promising therapeutic strategy for the prevention of HNSCC metastasis.

BackgroundDiabetic nephropathy (DN) is one of the vascular complications of diabetes and a leading cause of end-stage renal disease (ESRD) and mortality in diabetic patients. PANoptosis has been defined a unique form of programmed cell death that integrates pyroptosis, apoptosis, and necroptosis. However, the role of other biomarkers in modulating PANoptosis and their impact on DN remains unexplored.ObjectiveThis study aimed to explore panoptosis-related genes and potential therapeutic drugs in DN.MethodsWe downloaded DN datasets from the GEO database and identified differentially expressed genes (DEGs) through integrated differential expression analysis and weighted gene co-expression network analysis (WGCNA). The intersection between DN-related DEGs and panoptosis-related genes was obtained, and LASSO and SVM machine learning algorithms were applied to screen candidate biomarkers. The area under the receiver operating characteristic curve (AUC) was calculated for evaluation. Validation was performed using the merged dataset of GSE30529 and GSE4713. The CIBERSORT algorithm was used to assess immune cell infiltration, and Spearman correlation analysis was conducted to examine the association of biomarker genes. The Kidney Integrative Transcriptomics database was employed to explore the distribution of core genes across 12 cell populations. Potential drug molecules interacting with core genes were screened using the DSigDB database on the Enrichr platform, and molecular docking was performed using AutoDock Vina to evaluate binding affinity. The qRT-PCR was used to validate the expression of these hub mitochondria-related genes.ResultsAnalysis of the DN dataset yielded 17 intersecting genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses revealed that these genes were significantly associated with immune and inflammatory responses, pyroptosis, extrinsic apoptosis, necroptosis, and related pathways. Using LASSO and SVM machine learning algorithms, eight candidate biomarkers were identified: CD44, CRIP1, CEBPB, TNFRSF1B, CAV1, IGF1, GZMB, and LY96. ROC curve analysis demonstrated that these biomarkers had strong diagnostic value for DN patients. Further investigation into immune infiltration in DN samples using CIBERSORT showed that core genes were closely related to dendritic cells (resting), macrophages (M1), mast cells (activated), neutrophils, T cells (CD4 memory activated, CD4 memory resting, CD8, and gamma delta). Drug screening via DSigDB on Enrichr identified imatinib as a significantly enriched drug interacting with core genes, and molecular docking confirmed its strong binding affinity.ConclusionThrough comprehensive bioinformatics approaches, this study identified CD44, CRIP1, CEBPB, TNFRSF1B, CAV1, IGF1, GZMB and LY96 as potential diagnostic biomarkers for DN, providing new insights into disease diagnosis.

Extracellular vesicles (EVs) are emerging as a new mechanism of intercellular communication in renal disease. EVs originating from the renal system can be readily detected in urine and may therefore represent a promising component of liquid biopsies for use in the diagnosis and prognosis of renal disease. Recent studies have also indicated that EVs may have applications as therapeutic agents and vectors for drug delivery in renal diseases. Herein, we describe the recent progress in understanding the roles of EVs in renal pathophysiology and discuss EV-based therapy in kidney disease. Importantly, we focus on advances in the methodologies used for urine EV profiling and identification of potential biomarkers of renal disease in urine EVs.

BACKGROUND:Dysfunction in the processes of autophagy and apoptosis within renal tubular epithelial cells (RTEc) contributes to renal ischemia-reperfusion injury (IRI). However, the factors influencing this dysfunction remain unclear. Leucine-rich alpha-2-glycoprotein 1 (Lrg1) plays a role in the progression of diabetic nephropathy and kidney fibrosis by modulating the activin receptor-like kinase 1 (ALK1)-Smad1/5/8 and TGF-β1/Smad3 pathways, respectively. Therefore, we aimed to investigate whether Lrg1 is involved in the pathological mechanisms of renal IRI and whether its effects are related to the dysregulation of autophagy and apoptosis in RTEc. METHODS:We conducted in vitro and in vivo experiments using CoCl2-induced hypoxic human kidney-2 (HK-2) cells and mice with renal IRI, respectively. Lrg1 was silenced using siRNA and lentiviral vectors in HK-2 cells and mouse kidneys. Rapamycin (Rapa) and methyladenine were applied to regulate autophagy in renal IRI models. RESULTS:Increased Lrg1 expression was observed in hypoxic HK-2 cells and in the kidneys of mice with renal IRI. Silencing of Lrg1 through siRNA and lentiviral approaches restored autophagy and suppressed apoptosis in CoCl2-induced hypoxic HK-2 cells and renal IRI models. Additionally, reduced Lrg1 expression alleviated kidney damage caused by renal IRI. The downregulation of Lrg1 expression restrained the TGFβ-Smad1/5 signaling pathway in hypoxic-induced HK-2 cells and renal IRI by reducing ALK1 expression. Lastly, the enhancement of autophagy, achieved through Rapa treatment, provided protection against renal IRI in mice. CONCLUSIONS:Our findings suggest that Lrg1 silencing can be applied as a potential therapeutic target to inhibit the TGFβ1-Smad1/5 pathway, thereby enhancing autophagy and decreasing apoptosis in patients with acute kidney injury.

Acute kidney injury (AKI) is one of the most common clinical critical illnesses, with decreased glomerular filtration rate, retention of nitrogen products, water and electrolyte disorders, and acid-base imbalance as the main clinical manifestations. Presently, there is no effective treatment for acute kidney injury, but the main treatment is to cure the primary disease, remove risk factors, maintain acid-base and water-electrolyte balance, and undergo kidney replacement. However, the mortality rate is still high. Investigations and studies showed that the mortality rate of patients with acute kidney injury in the ICU is 5-80% [1]. In recent years, Chinese medicine has been widely used in acute kidney injury treatment due to its complete dialectical system and rich experience. Astragalus is a commonly used medicine in traditional Chinese medicine to treat acute kidney injury. Astragaloside IV is the main active component of traditional Chinese medicine, Astragalus membranaceus. This article summarizes the relevant studies on treating acute kidney injury with astragaloside IV.

Background: To explore the relationship of insulin resistance (IR) with chronic kidney disease (CKD) in individuals without diabetes. Methods: We performed a cross-sectional survey among 2142 community-based participants without diabetes from southern China from June to October 2012 and excluded the incomplete data. We divided all the participants into four groups according to the quartiles of homeostasis model assessment of IR (HOMA-IR). Logistic regression models were used to explore the associations of IR with CKD in these subjects. Results: In the unadjusted model, compared with the quartile one group, IR was significantly associated with CKD (odds ratio [OR] = 2.24, P < 0.001; OR = 4.46, P < 0.001) in the quartile three and four groups, and the association was still significant (OR = 2.08, P = 0.005; OR = 3.89, P < 0.001 ) after adjusting for potential confounders (including age, current smoker, current alcohol use, physical inactivity, education level, systolic blood pressure, diastolic blood pressure, serum triglyceride, and body mass index). The area under the receiver operating characteristic curve (95% confidence interval) of HOMA-IR for diagnosing CKD was 0.67 (0.64, 0.71). The cut-off value was 2.5, the sensitivity was 75.2%, and the specificity was 56.4%. Conclusions: HOMA-IR is associated with CKD in participants without diabetes. Early intervention for IR is important for reducing the incidence of CKD.

Purpose: The tissue inhibitor of metalloproteinase 2 (TIMP2), a natural inhibitor of matrix metalloproteinase (MMP), regulates inflammation, fibrosis, and cell proliferation. Chronic renal allograft dysfunction (CRAD) is a primary factor affecting the long-term survival of renal allografts. We assessed whether up-regulation of TIMP2 expression may affect the ERK1/2-NF-kappa B signaling pathway and CRAD development. Methods: Lewis rats received orthotopic F344 kidney allografts to establish the classical CRAD model. The treatment group was injected with a lentivirus encoding a TIMP2-targeting small hairpin (sh)RNA (LTS) at 5 x 108 TU/ml monthly after kidney transplantation. A second CRAD group was injected with a lentivirus TIMP2control vector (LTC). After 12 weeks, blood, urine, and kidney tissue were harvested to evaluate renal function and pathological examinations. Hematoxylin and eosin staining, Masson staining, and Periodic acid-Schiff staining were performed for renal histopathological evaluation according to the Banff criteria. TIMP2, phospho (p)-ERK1/2, p-p65 (NF-kappa B) expression levels were measured via immunohistochemical and Western blot analyses. Results: Compared to the F344 and Lewis control groups, the expression of TIMP2, p-ERK1/2, and p-p65 were significantly higher in the CRAD and CRAD+LTC renal tissues (p < 0.05). There were also increased levels of serum creatinine, nitrogen, and 24 h urinary protein in these two groups (p < 0.05). Typical histopathological changes of CRAD were observed in the CRAD and CRAD+LTC groups. Administration of LTS effectively decreased the expression of TIMP2, p-ERK1/2, and p-P65, and reduced interstitial fibrosis and macrophage infiltration in the treatment group (p < 0.05). Additionally, MCP1 and ICAM-1, which are downstream cytokines of the NF-kappa B pathway, were also inhibited in the renal rat kidney from the LTS group (p < 0.05). Furthermore, renal function was well preserved in the LTS group compared to the CRAD group and CRAD+LTC group. Conclusion: A decrease of TIMP2 can alleviate the progression of inflammation in CRAD via inhibition of the ERK1/2-NF-kappa B signaling pathway.

BackgroundRetinol binding protein 4 (RBP4), as a novel adipokine, has been proven to be highly related to insulin resistance, obesity, diabetes, hypertension, hyperuricemia and other metabolic diseases, which are all risk factors for chronic kidney disease (CKD). However, there is a lack of sufficient studies to explore the relationship between RBP4 and CKD, and no reports have described the predictive value of RBP4 for CKD. This study was designed to clarify the relationship between RBP4 and CKD and its potential predictive value.MethodsOur team has conducted a large-scale cross-sectional survey that contained 2117 individuals on the southern coast of China. Correlation test, logistic regression analysis were used to evaluate the association between RBP4 and CKD. Receiver operating characteristic (ROC) were used to evaluate the optimal cut-off and predictive value of RBP4 for predicting CKD.ResultsBy using the quartile grouping method, the population was divided into four groups according to the RBP4 level. As the RBP4 level increased, the prevalence of CKD also gradually increased among different groups. RBP4 was also correlated with various metabolic risk factors, such as blood glucose, blood lipids, blood pressure, waist circumference, uric acid, and with kidney function indicators such as creatinine, urine protein. Logistic regression analysis found that after adjusting for confounders, RBP4 remained significantly associated with CKD, independent of metabolic risk factors. ROC analysis showed that RBP4 as a single index, AUC (0.666) was superior to Scr, FBG, Log HOMA-IR, WC, TG, VLDL-C, UA, HDL-C, LDL-C, and that combining RBP4 indicator and other common risk factors of CKD can improve the accuracy for predicting CKD.ConclusionThis study found that the RBP4 was strongly correlated with CKD, RBP4 may become a valuable marker and have strong power for predicting CKD.

Background:The annual prevalence of metabolic syndrome (MetS) is increasing. Therefore, early screening and recognition of MetS are critical. This study aimed to evaluate the association between high-density lipoprotein (HDL) subclasses and MetS and to examine whether they could serve as early indicators in a Chinese community-based population with normal high-density lipoprotein cholesterol (HDL-C) levels. Methods:We used microfluidic chip technology to measure HDL subclasses in 463 people with normal HDL levels in 2018. We assessed how HDL subclasses correlated with and predicted insulin resistance (IR) and metabolic syndrome (MetS), evaluated by homeostatic model insulin resistance index (HOMA-IR) and the 2009 International Diabetes Federation (IDF), the American Heart Association (AHA), and the National Heart, Lung, and Blood Institute (NHLBI) criteria, respectively. We used correlation tests and ROC curves for the analysis. Results:The results indicate that there was a negative association between HDL2b% and the risk of IR and MetS in both sexes. Subjects in the highest quartile of HDL2b% had a significantly lower prevalence of IR and MetS than those in the lowest quartile (P<0.01). Correlation analysis between HDL2b% and metabolic risk factors showed that HDL2b% had a stronger association with these factors than HDL-C did in both sexes. ROC curve analysis also showed that HDL2b% had significant diagnostic value for IR and MetS compared to other lipid indicators. Conclusion:This study showed that MetS alters the distribution of HDL subclasses even when HDL-C levels are within the normal range. HDL-2b% has better diagnostic value for IR and MetS than HDL-C alone and may be a useful marker for early screening.

Introduction: Inflammation plays a key role in chronic kidney disease (CKD). Monocyte-to-lymphocyte ratio (MLR) is a novel inflammatory marker. The purpose of this study was to evaluate the relationship between MLR and inflammation in CKD patients. Methods: In total, 1,809 subjects were recruited from Wanzhai Town, Zhuhai City, between December 2017 and March 2018 for a cross-sectional survey. Patients were categorized based on the absence (hypersensitive C-reactive protein [hsCRP] level <= 3 mg/L) or presence (hsCRP level >3 mg/L) of inflammation. Logistic regression models and MLR quartiles were used to explore the relationship between MLR and inflammation in CKD patients. Results: Among 1,809 subjects, 403 (22.2%) had CKD. Significant differences in systolic blood pressure, estimated glomerular filtration rate, white blood cell (WBC), neutrophil, monocyte, MLR, and interleukin-6 (IL-6) levels were observed between noninflammatory group and inflammatory group. The highest MLR quartile had higher Scr, WBC, neutrophil, monocyte, IL-6, and hsCRP values and lower eGFR and lymphocyte values. Comparing the lowest quartile of MLR, the OR (95% CI) of inflammation risk in the highest quartile was 2.30 (1.24-4.27) after adjustment for confounding factors. The area under the curve of MLR for predicting inflammation was 0.631. The cutoff point for the MLR was 0.153. Conclusion: A high MLR was significantly and independently associated with inflammation in patients with CKD, making MLR a potential marker for inflammation in this demographic. MLR may also predict the severity of CKD. (c) 2024 The Author(s).Published by S. Karger AG, Basel

Background: Obesity and insulin resistance (IR) are positively associated with chronic kidney disease (CKD). Previous studies have identified triglyceride-glucose index (TyG) as a valuable surrogate of insulin resistance. Recently, new indicators combining TyG and simple anthropometric indices have emerged, The objective of this study was to assess the diagnostic accuracy of TyG and newly TyG related indicators in detecting CKD and explore which indices were superior in associating with CKD in Chinese population. Methods: Correlation test, logistic regression analysis, and receiver operating characteristic (ROC) analyses were used to evaluate the optimal cut-off and value of TyG, TyG-body mass index (TyG-BMI), TyG-waist circumference (TyG-WC), TyG-waist to height ratio (TyG-WHtR) for predicting CKD. Results: TyG-WHtR, TyG-WC, and TyG-BMI correlated with several risk factors for CKD. After adjusting for confounders, TyGWHtR and TyG-WC remained significantly associated with CKD, while TyG-BMI did not. The highest quartiles of TyG-WHtR and TyG-WC had 1.95- and 1.91-fold increased risk of CKD than the lowest quartiles (P<0.05). TyG-WHtR had the largest AUC (0.687) for CKD detection, followed by TyG-WC (0.669), TyG (0.652), and TyG-BMI (0.648). A united model that involved TyG-WHtR and other risk variables had higher predictive performance (AUC=0.791) than a single TyG related indicator. However, TyG had the highest OR (2.713, 95% CI, 1.446-5.090) for reduced eGFR in the fully adjusted model. A united model that involved TyG and WHtR separately had stronger predictive ability (AUC: 0.794) than the model that involved TyG-WHtR individually (AUC:0.791). Conclusion: This study found that TyG-WHtR had a better diagnostic value in the diagnosis of CKD, compared to other TyG related indicators, but none of the TyG related indicators showed a stronger association with CKD than TyG. Further research and more refined algorithms are needed to verify these new indicators.

Background：Chronic kidney disease is currently a major public health challenge worldwide, and modeling based on gene expression profiling is essential to guide individualized treatment of the disease. According to recent studies, cuprotosis, one of the forms of death of cells, appears to contribute to the progression of various diseases. Therefore, the present study aims to explore clusters associated with cuprotosis genes in chronic kidney disease, delve into immune infiltration, and construct predictive models. Methods：The GSE37171 (GPL570) dataset was downloaded from the Gene Expression Omnibus for analyzing expression profiling and immune characterization of cuprotosis regulators in CKD. Samples were classified into different clusters based on cuprotosis-related genes (CRGs) of kidney disease. Differential expression pathways and biological functions among clusters were identified through gene set variation analysis. The weighted gene co-expression network analysis algorithm was adopted to identify specific differentially expressed genes of clusters. A machine learning model was built to construct and validate nomogram risk prediction maps. Results：A total of seven cuprotosis-related genes are differential genes between chronic kidney disease and control group, with differences in immune infiltration between the two groups. Two different clusters are identified based on the expression profiles of the cuprotosis-related genes. And according to the differences in immune infiltration, it is hypothesized that the prognosis of Cluster 2 may be worse. Cluster 1 may be associated with cellular lipid anabolism, fibrosis, signal reception, inflammation, and other processes, while Cluster 2 is more closely related to DNA replication and binding, cellular protein synthesis and transport, peroxisome, etc. The predictive performance of the four selected machine learning classifiers is compared and a prediction model is developed, which provides the highest predictive validity in the test cohort (AUC = 0.992), indicating satisfactory performance. The model is verified to exhibit good predictive efficacy. Conclusion：The study systematically illustrates the complex relationship between cuprotosis and chronic kidney disease and develops a promising predictive model to assess cuprotosis subtypes in patients with the disease, revealing the underlying molecular mechanisms that lead to its

Retinoic acid is an active metabolite with significant physiological functions in human development, immunity, vision, and skin health. In recent years, research on retinoic acid in the field of kidney disorders has been increasing gradually. Yet, there is a lack of systematic bibliometric analysis of retinoic acid research in the kidney domain. This study included 1,368 articles published between 1998 and 2023 on treating kidney diseases with retinoic acid. Using the bibliometric analysis software VOSviewer and CiteSpace, we analyzed data on publication trends, contributing countries and institutions, journals and cocited journals, authors and cocited authors, cocited references, research hotspots, and frontiers. On the basis of the results of the bibliometric analysis, we identified the research efforts and their developmental trends, providing the groundwork for future research on retinoic acid.

BackgroundUrinary extracellular vesicles (uEVs) are derived from epithelia facing the renal tubule lumen in the kidney and urogenital tract; they may carry protein biomarkers of renal dysfunction and structural injury. However, there are scarce studies focusing on uEVs in diabetes with kidney injury.Materials and methodsA community-based epidemiological survey was performed, and the participants were randomly selected for our study. uEVs were enriched by dehydrated dialysis method, quantified by Coomassie Bradford protein assay, and adjusted by urinary creatinine (UCr). Then, they identified by transmission electron microscopy (TEM), nanoparticle track analysis (NTA), and western blot of tumor susceptibility gene 101.ResultsDecent uEVs with a homogeneous distribution were finally obtained, presenting a membrane-encapsulated structure like cup-shaped or roundish under TEM, having active Brownian motion, and presenting the main peak between 55 and 110 nm under NTA. The Bradford protein assay showed that the protein concentrations of uEVs were 0.02 ± 0.02, 0.04 ± 0.05, 0.05 ± 0.04, 0.07 ± 0.08, and 0.11 ± 0.15 μg/mg UCr, respectively, in normal controls and in prediabetes, diabetes with normal proteinuria, diabetes with microalbuminuria, and diabetes with macroproteinuria groups after adjusting the protein concentration with UCr by calculating the vesicles-to-creatinine ratio.ConclusionThe protein concentration of uEVs in diabetes with kidney injury increased significantly than the normal controls before and after adjusting the UCr. Therefore, diabetes with kidney injury may change the abundance and cargo of uEVs, which may be involved in the physiological and pathological changes of diabetes.

Background: To observe the short-term outcome of plasma adsorption PA therapy in amyotrophic lateral sclerosis (ALS). Methods: 28 cases of als patients were recruited in this study, of which 20 were male and 8 were female with a mean age of 53.21±9.07 years and the average course of 33±23.35 months. The clinical manifestations were limb weakness (N=27), muscular atrophy (N=27), muscular tremor (N=5), dysphagia (N=12) and dysarthria (N=12). The clinical data of the patients recruited were graded by Amyotrophic Lateral Sclerosis Functional Rating Scale Revised (ALSFRSR) : <10 (N=1), 11-20 (N=4), 21-30 (N=6), 31-40 (N=12), >40 (N=5). All patients received PA therapy once a week for three successive times after examining the conditions of blood coagulation and virus infection. PA therapy was supplemented with neurotrophic therapy meanwhile. All patients' clinical manifestations and scores of ALSFRSR before treatment and one week after treatment were evaluated and compared. The levels of serum superoxide dismutase (SOD), interleukin-10 (IL-10), serum creatine kinase (CK) and lactate dehydrogenase (LDH) before and after treatment were compared. Results: After PA therapy, 14 patients have improved obviously in muscle strength, 4 patients in hypermyotonia partially, 3 patients in muscular tremor, 5 patients in dysarthria, 3 patients in salivation to some extent and 2 patients in swallowing function. The score of ALSFRSR after PA treatment (31.89±10.36) was remarkably higher than that before PA treatment (30.68±10.52) (P<0.01). The levels of SOD (155.10±21.87 IU/L) and IL-10 (138.06±185.88 pg/mL) after PA treatment were significantly higher than the levels before PA treatment (143.08.3±19.16 IU/L and 46.34±75.31 pg/mL, respectively) (P<0.05). The levels of CK (168.86±113.50 IU/L) and LDH (152.07±32.65 IU/L) after PA treatment were significantly lower than the levels before PA treatment (356.68±250.30 IU/L and 181.36±33.74 IU/L respectively) (P<0.01). At the end of follow-up period (November, 2019), five patients died of respiratory failure 16-21 months after PA treatment and two patents died of respiratory infection 15-20 months after PA treatment. 7 patients were still alive. The score of ALSFRS-R of these patients who survived at the end of follow-up (13.00±13.37) were significantly lower than before PA treatment (36.71±8.56) (P<0.05) and after PA treatment (38.14±8.82) (P<0.05). Conclusions: Plasma adsorption (PA) therapy has shortterm therapeutic effects on als. The effects might be attributed to the anti-oxygen free radical effect by increasing SOD level and the anti-inflammation effect by increasing IL-10 level. As the efficacy of PA therapy was obtained in a small sample size and short follow-up period, the longterm observation of PA efficacy in treating als should be further investigated.

INTRODUCTION:Acute kidney injury (AKI) is a clinical emergency caused by the rapid decline of renal function caused by various etiologies. Growth differentiation factor 11 (GDF11) can promote renal tubular regeneration and improve kidney function in AKI, but the specific mechanism remains unclear. Herein, we investigated the effect and mechanisms of GDF11 in ameliorating AKI induced by ischemia-reperfusion (I/R).METHODS:An animal model of AKI was established by I/R method, and the changes of serum urea nitrogen and creatinine were measured to evaluate the AKI. Enzyme-linked immunosorbent assay (ELISA) was used to measure cytokines, malondialdehyde, superoxide dismutase, nitric oxide synthase, and arginase 1 levels. Flow cytometry was used to count the M1/M2 macrophages. IHC, WB, and q-PCR experiments were used to evaluate the expression of GDF11.RESULTS:The changes in serum levels of urea nitrogen and creatinine after I/R suggest that an animal model of AKI induced by I/R was successfully established. AKI caused by I/R significantly changed the M1/M2 macrophage polarization balance, with an increase in M2 being significantly higher than M1 as well as increased oxidative stress. Treatment with GDF11 after I/R significantly increased the differentiation of M2 cells and inhibited the differentiation of M1 macrophages, as well as decreased oxidative stress.CONCLUSION:GDF11 can promote the repair of AKI caused by I/R by regulating the balance of M1/M2 polarization in macrophages and oxidative stress.

Resumo A aterosclerose é a causa mais comum de doença cardiovascular em todo o mundo, ela está associada a uma alta incidência de eventos clínicos. O acúmulo de evidências elucidou que os RNAs longos não codificantes (LncRNAs) são uma nova classe de transcritos com papéis críticos nos processos fisiopatológicos da aterosclerose. Nesta revisão, resumimos o progresso recente dos LncRNAs no desenvolvimento da aterosclerose. Descrevemos principalmente os diversos mecanismos regulatórios dos LncRNAs nos níveis transcricionais e pós-transcricionais. Este estudo pode fornecer informações úteis sobre os LncRNAs como alvos terapêuticos ou biomarcadores para o tratamento da aterosclerose.

1Department of Nephrology, The Third Affiliated Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 2Department of Nephrology, Shenzhen Hospital, Southern Medical University, Shenzhen, People’s Republic of China; 3Department of Nephrology, South China Hospital of Shenzhen University, Shenzhen, People’s Republic of China; 4Department of Nephrology, The First Dongguan Affiliated Hospital of Guangdong Medical University, Dongguan, People’s Republic of China

Purpose The improvement of the long-term survival of patients receiving kidney transplantation remains challenging. Ischemia reperfusion injury (IRI) reduces long-term renal graft survival in the early posttransplantation phase. However, few studies have investigated the effects of IRI on the pathogenesis of chronic renal graft failure. Silent information regulator 1 (SIRT1) regulates antioxidative stress and inflammatory response and protects against IRI. This study is aimed at investigating the role of resveratrol (RSV), an SIRT1 activator, in preventing renal injury in a rat renal transplantation model. Methods A classical F334-to-LEW orthotopic renal transplantation rat model was established. The experiment group was treated with RSV from three days prior to kidney transplantation and the treatment lasted until the day of harvest. Uninephrectomized F344 and Lewis rats were used as controls. After 12 weeks, the effects of RSV were evaluated according to renal function, histopathology, immunohistochemistry, and western blotting. The activities of oxidative stress-related markers and proinflammatory cytokines were also assessed. Results RSV treatment significantly ameliorated renal function and histopathological lesions in kidney-transplanted rats and increased the levels of GSH, SOD, and CAT and decreased the levels of MDA and iNOS. Furthermore, RSV also inhibited the expression of proinflammatory cytokines/chemokines such as TNF-α, CD68, and IL-6 in kidney-transplanted rats. In addition, the transplant group displayed significantly lower level of SIRT1 and higher level of Ac-NF-κBp65. RSV increased the expression of SIRT1 and decreased the expression of Ac-NF-κBp65. Conclusion SIRT1 plays an important role in the pathogenesis of chronic renal allograft dysfunction. It is a potential therapeutic agent for ameliorating inflammation and oxidative stress-induced renal injury following kidney transplantation by activating the SIRT1/NF-κB signaling pathway.