Effects of uric acid-lowering therapy (ULT) on renal outcomes in CKD patients with asymptomatic hyperuricemia: a systematic review and meta-analysis.

BACKGROUND: It is well known that asymptomatic hyperuricemia and gout play an important role in patients with chronic kidney disease (CKD). However, the effect of uric acid-lowering therapy (ULT) on the prognosis of CKD patients with asymptomatic hyperuricemia remains controversial. Therefore, we aim to investigate the influence of ULT on renal outcomes in these patients. METHODS: Comprehensive searches were conducted in PubMed, EMBASE, China National Knowledge Internet (CNKI), and the Cochrane Library, up until January 2024. We included randomized controlled trials (RCTs) that evaluated the effects of ULT on renal outcomes in CKD patients with asymptomatic hyperuricemia. RESULTS: A total of 17 studies were included in the meta-analysis. Compared with placebo or no treatment, ULT preserved the loss of estimated glomerular filtrating rate (eGFR) (Weighted mean difference [WMD] and its 95% confidence intercal(CI): 2.07 [0.15,3.98] mL/min/1.73m2) at long-term subgroup. At the same time, short-term subgroup also proved the preserved loss of eGFR (WMD 5.74[2.09, 9.39] mL/min/1.73m2). Compared with placebo or no treatment, ULT also reduced the increase in serum creatinine (Scr) at short-term (WMD -44.48[-84.03,-4.92]µmol/L) subgroup and long-term (WMD -46.13[-65.64,-26.62]µmol/L) subgroup. ULT was associated with lower incidence of the events of doubling of Scr without dialysis (relative risk (RR) 0.32 [0.21, 0.49], p < 0.001). However, no difference was found for lower incidence of acute kidney injury (AKI) (p = 0.943). CONCLUSIONS: According to our study, ULT is beneficial for slowing CKD progression both in short to long-term follow-ups. Additionally, in patients younger than 60 years old, the protective effect of ULT on renal outcome is more pronounced. However, it showed no significant difference in the incidence of AKI. These findings underscore the importance of considering ULT in clinical strategies for CKD patients with asymptomatic hyperuricemia.

Total Synthesis and Stereochemistry Assignment of Nucleoside Antibiotic A-94964.

A collective total synthesis of eight diastereoisomers associated with NMR analysis leads to a full stereochemistry assignment of the structurally unique nucleoside antibiotic A-94964, which features an octuronic acid uridine core decorated with an α-D-mannopyranosyl residue and an α-D-N-acylglucosaminopyranosyl residue via a phosphodiester bridge.

Synthesis of Sea Cucumber Saponins with Antitumor Activities.

Holostane glycosides are characteristic metabolites of sea cucumbers, which possess various biological activities. Here, we report the synthesis of two representative congeners, namely, pervicoside B and C, starting from lanosterol with the longest linear sequence of both 34 steps and in 0.3% overall yields. The flexible synthetic approach has enabled us to expeditiously prepare 16 analogues for preliminary studies on the key structural features influencing their antiproliferative activities against tumor cells. A simplified disaccharide is found to be as potent as natural tetrasaccharides, which can be used as a lead for future studies.

Remote Ischemic Preconditioning Reduces the Risk of Contrast-Induced Nephropathy in Patients with Moderate Renal Impairment Undergoing Percutaneous Coronary Angiography: A Meta-Analysis.

BACKGROUND/AIMS: This meta-analysis evaluated the effects of remote ischemic preconditioning (RIPC) on the risk of contrast-induced nephropathy (CIN) in patients undergoing percutaneous coronary intervention/coronary angiography (PCI/CA). METHODS: PubMed, Embase, and the Cochrane Central Register of Controlled Trials databases were searched for randomized controlled trials (RCTs) that assessed the effect of RIPC on CIN in patients undergoing PCI/CA. The main outcomes of interest were the incidence of CIN 48-72 h after CA, the levels of serum creatinine, cystatin C, neutrophil gelatinase-associated lipocalin, and estimated glomerular filtration rate (eGFR), mortality, and requirement of hemodialysis and rehospitalization. The analysis was conducted using the random-effect model due to the expected heterogeneity among different studies. RESULTS: In total, 16 trials covering 2,048 patients were identified. By assessing the methodological quality of the included studies through the Coch-rane risk of bias, we found that of the 16 RCTs, 3 had a low risk of bias, 6 a high, and 7 an unclear risk. The application of RIPC decreased the incidence of CIN (relative risk, RR, 0.50, 95% confidence interval, CI, 0.39-0.65; p < 0.001). Subgroup analyses showed that RIPC decreased the incidence of CIN in patients with eGFR <60 mL/min/1.73 m2 (RR 0.53, 95% CI 0.38-0.75; p < 0.001) but not in patients with eGRF ≥60 mL/min/1.73 m2 (RR 0.82, 95% CI 0.35-1.94; p = 0.66) at baseline. Furthermore, the increase in serum creatinine was significantly lower in patients with RIPC compared to control patients (standardized mean difference -1.41, 95% CI -2.46 to -0.35; p = 0.009). CONCLUSIONS: Based on 16 RCTs, this meta-analysis shows that RIPC can reduce the risk of CIN in patients with moderate renal impairment undergoing PCI/CA. However, this needs to be confirmed by further high-quality evidence.

Chemical synthesis of marine saponins.

Covering: 1989-2017 Saponins are characteristic metabolites of starfish and sea cucumbers, and occasionally are also found in sponges, soft coral, and small fish. These steroid or triterpenoid glycosides often show remarkable biological and pharmacological activities, such as antifungal, antifouling, shark repellent, antitumor and anti-inflammatory activities. Over one thousand marine saponins have been characterized; the majority of them can be categorized into three major structural types, i.e., asterosaponins, polyhydroxysteroid glycosides, and holostane glycosides. Thus far, only 12 marine saponins have been synthesized; those representing the major types were successfully synthesized recently. The syntheses involve preparation of the aglycones from the terrestrial steroid or triterpene materials, installation of the carbohydrate units, and manipulation of the protecting groups. Herein, we provide a comprehensive review on these syntheses.

Delayed administration of suramin attenuates peritoneal fibrosis in rats.

BACKGROUND: Peritoneal fibrosis is the most common complication of peritoneal dialysis, but there is currently no effective treatment. We previously reported that suramin pretreatment prevents the development of peritoneal fibrosis in a rat model of peritoneal fibrosis induced by chlorhexidine gluconate (CG). Here, we further examined the effectiveness of delayed administration of suramin on peritoneal fibrosis and the mechanism (s) involved in this process. METHODS: In the rat model of peritoneal fibrosis induced by CG, suramin or saline was administered at day 21 and 28. All rats were then sacrificed to collect peritoneal tissues for Western blot analysis and histological staining at day 35. RESULTS: Our results demonstrated that delayed administration of suramin starting at 21 days following CG injection can ameliorate peritoneal damage, with greater efficacy after two injections. Suramin also reduced the expression of α-smooth muscle actin, Collagen 1, and Fibronectin and suppressed phosphorylation of Smad-3, epidermal growth factor receptor (EGFR), signal transducers, activator of transcription 3 (STAT3) as well as extracellular signal-regulated kinases 1/2 (ERK 1/2) in the peritoneum injured with CG. Moreover, delayed administration of suramin inhibited overproduction of transforming growth factor-ß1(TGF-ß1) and expression of several pro-inflammatory cytokines, including monocyte chemoattractant protein-1, tumor necrosis factor-α, interleukin-1, and interleukin-6. CONCLUSIONS: Our results indicated that suramin can attenuate progression of peritoneal fibrosis by a mechanism involving inhibition of the TGF-ß1/Smad3 and EGFR signaling pathways as well as suppression of multiple proinflammatory cytokines. Thus, suramin may have the potential to offer an effective treatment for peritoneal fibrosis.

Zr2Si: an antiferromagnetic Dirac MXene.

MXenes, which constitute a kind of graphene-like material, have been intensively investigated due to their applications in future nanoelectronics technology. These MXenes are either metallic or semiconducting, whereas Dirac cones similar to graphene have rarely been reported. Using first-principles calculations, we proposed a new MXene, namely Zr2Si, whose antiferromagnetic (AFM) ground state exhibited in these calculations anisotropic Dirac cones with Fermi velocities comparable to that in graphene. The Dirac spectrum here was determined to arise mainly from the dx2-y2 and dz2 orbitals of Zr atoms. Additionally, the Dirac cones can be gapped when taking the spin-orbit coupling (SOC) and Coulomb repulsive interaction (U) into account, which opens an avenue for using the Zr2Si MXene for electronics applications.

Identification of chronic kidney disease risk in relatively lean Southern Chinese: the hypertriglyceridemic waist phenotype vs. anthropometric indexes.

PURPOSE: Assessing and comparing the ability of the hypertriglyceridemic waist (HW) phenotype and anthropometric obesity indexes to identify subjects at high risk of chronic kidney disease (CKD) in a relatively lean population in South China. METHODS: Using data from a community-based, cross-sectional study conducted in Zhuhai City, Southern China, we examined associations between the HW phenotype, anthropometric obesity indexes, and incident CKD risk in a relatively lean population. Multiple logistic regression analyses were used to evaluate the associations. RESULTS: The HW phenotype associated with CKD significantly in the unadjusted analysis (OR 3.53, 95% CI 1.65-7.52, P = 0.001). Further adjustment for gender, age, and other potential confounding variables had an impact on the odd ratios (OR); the OR decreased but still existed (OR 2.91, 95% 1.23-6.87, P = 0.016). The association of the HW phenotype with CKD remained significant after further adjustment for hypertension and diabetes. No significant association between the anthropometric indexes and incident CKD was found. CONCLUSION: The HW phenotype, but not the anthropometric indexes, is associated with an elevated risk of CKD in relatively lean subjects. The HW phenotype appears to be a better predictor of CKD than the anthropometric indexes. LEVEL OF EVIDENCE: Level V, descriptive study.

Total Synthesis of Echinoside†A, a Representative Triterpene Glycoside of Sea Cucumbers.

Echinoside A, a sulfonylated holostane tetrasaccharide with potent anticancer and antifungal activity, was synthesized in a longest linear sequence of 35 steps and 0.6 % overall yield. The synthetic approach is adaptable to the synthesis of congeners and analogues, as exemplified by the ready synthesis of ds-echinoside A and echinoside B, and thus will facilitate in-depth studies on the promising biological effects of echinoside A. Moreover, the present synthesis demonstrates the feasibility of synthetic access to the characteristic complex triterpene glycosides that occur ubiquitously in sea cucumbers.

Metabolic syndrome and chronic kidney disease in a Southern Chinese population.

AIM: To explore the relationship between metabolic syndrome (MS) and risk for chronic kidney disease (CKD) in a Southern Chinese population. METHODS: A cross-sectional study was conducted in 1724 community-based Southern Chinese participants from June to October 2012. The prevalence of MS (as defined by the International Diabetes Federation) and CKD (defined as an estimated glomerular filtration rate of <60 mL/min per 1.73 m(2) and/or albuminuria) was determined. The association between MS and CKD was then analyzed using STATA software. RESULTS: Metabolic syndrome was significantly associated with CKD (P < 0.001) in the unadjusted analyses as well as after adjustment for potential confounders. The unadjusted odds ratio and adjusted odds ratio for MS were 3.53 (95% confidence interval (CI) 2.62 to 4.75, P < 0.001) and 2.52 (95% CI 1.84 to 3.54, P < 0.001). When further adjusted for diabetes and hypertension, the association of MS and CKD was significant (odds ratio (OR) 1.63, 95% CI 1.15 to 2.32, P = 0.006). After adjustment for potential confounders, three components and four/five components were associated with CKD. The OR for three components and four/five components were 2.90 (95% CI 1.70 to 4.96, P < 0.001) and 3.64(95% CI 1.95 to 6.80, P < 0.001), when compared with those without components. High blood pressure, high serum triglyceride level, elevated fasting glucose level and central obesity were associated with CKD (P < 0.05). The odds ratios for elevated blood pressure, elevated serum triglyceride levels, elevated fasting glucose and central obesity were 1.80 (95% CI 1.25 to 2.62, P = 0.002), 1.56 (95% CI 1.14 to 2.14, P = 0.006), 2.54 (95% CI 1.82 to 3.57, P < 0.001), and 1.50 (95% CI 1.10 to 2.07, P = 0.01), respectively. CONCLUSION: These findings suggest that MS is associated with CKD in Southern Chinese population, which may provide important information for the overall control of these diseases.

Central obesity, C-reactive protein and chronic kidney disease: a community-based cross-sectional study in southern China.

OBJECTIVE: Previous studies have shown that central obesity is associated with chronic kidney disease (CKD). We hypothesized that the association of central obesity with CKD is modified by the presence of inflammation. To test this hypothesis, we performed this study. METHODS: This was a cross-sectional study in southern China. Waist-to-height ratio (WHtR) was used as a central obesity index and C-reactive protein (CRP) was used as an index for inflammation. CKD was defined as estimated glomerular filtration rate(eGFR) <60 ml/min/1.73m(2) or albuminuria-to-creatinine ratio (ACR) >30mg/g. Multivariable logistic regressions were used and logistic regression models were adjusted for potential confounders and other components of metabolic syndrome. RESULTS: 1834 subjects were included in the current study. WHtR, body mass index and waist circumference were significantly associated with the level of CRP. When adjustment for potential confounders, only central obesity with a higher CRP level was associated with CKD (Relavitve-risk Ratio, 95% CI: 1.68, 1.03 - 2.75, P = 0.04). In multivariate logistic models, WHtR was associated with CKD. The odd ratio for WHtR (every SD increment), was 1.38 (95% CI 1.15, 1.66, P < 0.001). Further adjustment for log-transformed CRP had an impact on the odd ratios. CONCLUSION: Central obesity is associated with CKD, independently of other MetS components. Central obesity is also associated with inflammation and the presence of inflammation modifies the associations of central obesity and CKD. This study is based on a community-based chinese population, and the results may only be applicable for Chinese population.

Association of Anthropometric indexes with chronic kidney disease in a Chinese population.

OBJECTIVE: Obesity is associated with an increased risk of chronic kidney disease (CKD), but the best anthropometric obesity measure remains controversial. This study aimed to examine the associations of anthropometric indexes with CKD risk and which anthropometric index is a better predictor of CKD. METHODS: Data was drawn from a cross-sectional study in China. We used four anthropometric indexes: body mass index (BMI), waist circumference (WC), waist-to hip ratio (WHR), and waist-to-height ratio (WHtR). CKD was defined as estimated glomerular filtration rate (eGFR) < 60 ml/ min/1.73 m2 or urinary albumin to creatinine ratio (ACR) ≥ 30 mg/g. Logistic regressions were used for the analyses. RESULTS: 1,834 participants were included in the analyses. After adjusting for potential confounders, BMI, WC and WHtR were significantly associated with CKD in men and women. The respective odd ratios for BMI (every SD increment), WC (every SD increment), and WHtR (every SD increment) were 1.46, 1.40, and 1.45 in men as well as 1.21, 1.31, and 1.38 in women. After adjusting for potential confounders, WHR was associated with CKD in women but not men. In women, the associations of WC, WHR and WHtR with CKD was independent of other MetS components. No difference in WHtR was observed between men and women. CONCLUSION: Anthropometric indexes are associated with CKD. The associations of anthropometric indexes with CKD are independent of other MetS components in women but not men. In women, central obesity indexes are better than BMI for predicting of CKD.

Metabolic Syndrome Components and Chronic Kidney Disease in a Community Population Aged 40 Years and Older in Southern China: A Cross-Sectional Study.

Purpose: To investigate the correlation between metabolic syndrome components and chronic kidney disease (CKD) among a community population aged 40 years and older in Southern China. Patients and Methods: From December 2017 to March 2018, 1969 participants (male n = 715, female n = 1254) aged 40 years and older were recruited in Southern China for a cross-sectional survey. A logistic regression model was established to analyze the correlation between metabolic syndrome components and CKD. Results: Among the 1969 subjects, 407 (20.7%) were CKD patients, including 152 males (prevalence rate 21.3%) and 255 females (prevalence rate 20.3%). Anthropometric data (waist circumference, age, systolic and diastolic blood pressure), serum/plasma data (serum creatinine, serum uric acid, fasting plasma glucose, C-reactive protein, serum triglyceride), urinary and other findings (body mass index, waist-to-hip and waist-to-height ratios, urinary albumin to creatinine ratio, homeostasis model assessment of insulin resistance) were significantly higher in patients with than without CKD (P < 0.05). Metabolic syndrome and at least some of its components were statistically significant risk factors for CKD in models with and without adjustment for diabetes, obesity and hypertension. Conclusion: Metabolic syndrome and its single or combined components are independently associated with CKD in community populations aged 40 years and older. The correlation between some components and CKD remained significant in both non-diabetic and non-obese subjects. Correlations between components of metabolic syndrome and CKD show that it is feasible and necessary to carry out targeted screening and intervention tests in people aged 40 and over.

Amelioration of Renal Injury by Resveratrol in a Rat Renal Transplantation Model via Activation of the SIRT1/NF-κB Signaling Pathway.

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.

Associaton of Retinol Binding Protein 4 (RBP4) Levels With Hyperuricemia: A Cross-Sectional Study in a Chinese Population.

Background: There are few studies on predictive biomarkers for hyperuricemia, and the predictive value of these biomarkers tends to be poor. Additionally, no reports have described the predictive value of retinol binding protein 4 (RBP4) for hyperuricemia. Purpose: This study was performed to evaluate the value of RBP4 for predicting the risk of hyperuricemia in a general population, determine whether RBP4 could be used alone or in combination with other factors to predict the risk of hyperuricemia in the general population, and establish an optimum predictive model. Methods: We conducted a population-based cross-sectional survey in 2018, involving a questionnaire, physical examination, and laboratory testing. We enrolled 2303 individuals by stratified random sampling, and 2075 were included in the data analysis after applying the eligibility criteria. Results: Serum RBP4 level had a highly significant association with hyperuricemia (P<0.001). After adjusting for potential confounders, logistic regression indicated that the risk of hyperuricemia was highest in the highest RBP4 quartile (odds ratio: 7.9, 95% confidence interval [CI]: 4.18-14.84, compared to the lowest quartile). The area under the receiver operating characteristic (ROC) curve (AUC) for RBP4 was 0.749 (95% CI: 0.725-0.774, P<0.001), which was higher than that for all the other predictors assessed. The optimum model for predicting hyperuricemia in the general population consisted of RBP4, sex (male), body mass index, serum creatinine, high-sensitivity C-reactive protein, fasting blood glucose, insulin, and alcohol consumption. The AUC was 0.804 (95% CI: 0.782-0.826, P<0.001). Conclusions: RBP4 is strongly associated with hyperuricemia, and its predictive value was higher than that of traditional predictors.

Inhibition of Glycogen Synthase Kinase 3ß Alleviates Chronic Renal Allograft Dysfunction in Rats.

BACKGROUND: Chronic renal allograft dysfunction (CRAD) is a major condition that impedes the long-term survival of renal allografts. However, the mechanism of CRAD is obscure, and the effective strategies for controlling the progression of CRAD are lacking. The present study used a CRAD rat model to assess the effect of glycogen synthase kinase 3ß (GSK-3ß) inhibition on the development of CRAD. METHODS: A classical F334-to-LEW orthotopic renal transplantation was performed on the CRAD group. The treatment group was treated with the GSK-3ß inhibitor 4-benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione for 12 consecutive weeks following renal transplantation. The study included uninephrectomized F344 and Lewis rats as control subjects. Twelve weeks post surgery, the rats were retrieved for analysis of renal function, urine protein levels, histological, immunohistochemical, and molecular biological parameters. RESULTS: Administration of 4-benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione inactivated GSK-3ß and thereby improved renal function, attenuated proteinuria, and reduced renal tissue damage in CRAD rats. Besides, inactivation of GSK-3ß inhibited nuclear factor-κB activation, macrophage infiltration, and expression of multiple proinflammatory cytokines/chemokines. Inhibition of GSK-3ß also decreased the levels of malondialdehyde, increased superoxide dismutase levels, upregulated the expression of heme oxygenase-1 and NAD(P)H quinone oxidoreductase-1, and enhanced nuclear translocation of nuclear factor erythroid 2-related factor 2 in the kidneys of CRAD rats. CONCLUSIONS: Inhibition of GSK-3ß attenuates the development of CRAD by inhibiting inflammation and oxidant stress. Thus, GSK-3ß inhibition may represent a potential therapeutic strategy for the prevention and treatment of CRAD.

Multiple Dirac cones and Lifshitz transition in a two-dimensional Cairo lattice as a Hawking evaporation analogue.

The linear energy-momentum dispersion of Dirac cones offers a unique platform for mimicking the fantastical phenomena in high energy physics, such as Dirac fermions and black hole (BH) horizons. Three types of Dirac cones (I, III, and II) with different tilts have been proposed individually in specific materials but lack of integral lattice model. Here, we demonstrated the three types of Dirac cones inherited in aπ-conjugated Cairo lattice of double-degeneratedπandpzorbitals by means of tight-binding (TB) approach, which paves a way for the design of two-dimensional (2D) Dirac materials. From first-principles calculations, we predicted a candidate material,penta-NiSb2monolayer, to achieve these multiple Dirac cones and the Lifshitz transition between different Dirac cones driven by external biaxial strain. The coexistence of the three types of Dirac cones renderspenta-NiSb2monolayer a promising 2D fermionic analogue to simulate the event-horizon evaporation with a high Hawking temperature.

Pharmacologic Targeting of BET Proteins Attenuates Hyperuricemic Nephropathy in Rats.

Hyperuricemia is an independent risk factor for renal damage and promotes the progression of chronic kidney disease. In this study, we investigated the effect of I-BET151, a small-molecule inhibitor targeting the bromodomain and extraterminal (BET) proteins, on the development of hyperuricemic nephropathy (HN), and the mechanisms involved. Expression levels of bromodomain-containing protein 2 and 4, but not 3 were increased in the kidney of rats with HN; administration of I-BET151 effectively prevented renal dysfunction, decreased urine microalbumin, and attenuated renal fibrosis as indicated by reduced activation of renal interstitial fibroblasts and expression of fibronectin and collagen I in HN rats. Mechanistic studies show that I-BET151 treatment inhibited transition of renal epithelial cells to a mesenchymal cell type as evidenced by preservation of E-cadherin and reduction of vimentin expression. This was coincident with reduced expression of TGF-ß1 and dephosphorylation of Smad3 and ERK1/2. I-BET151 was also effective in inhibiting phosphorylation of NF-κB, expression of multiple cytokines and chemokines, and infiltration of macrophages to the injured kidney. Although there were increased serum levels of uric acid and xanthine oxidase, an enzyme that catalyzes production of uric acid, and decreased expression of renal organic anion transporter 1 and 3 that promote urate excretion in the model of HN, and reduced expression levels of urine uric acid, I-BET151 treatment did not affect these responses. Collectively, our results indicate that I-BET151 alleviates HN by inhibiting epithelial to mesenchymal transition and inflammation in association with blockade of TGF-ß, ERK1/2 and NF-κB signaling.

Potential role of anti-inflammatory HDL subclasses in metabolic unhealth/obesity.

High-density lipoprotein (HDL) particles comprising heterogeneous subclasses of different functions exert anti-inflammatory effects by interacting with immune-response cells. However, the relationship of HDL subclasses with immune-response cells in metabolic unhealth/obesity has not been defined clearly. The purpose of this study was to delineate the relational changes of HDL subclasses with immune cells and inflammatory markers in metabolic unhealth/obesity to understand the role of anti-inflammatory HDL subclasses. A total of 316 participants were classified by metabolic health. HDL subclasses were detected by microfluidic chip electrophoresis. White blood cell (WBC) counts and lymphocytes were assessed using automatic haematology analyser. Levels of high-sensitivity C-reactive protein (hs-CRP) and interleukin 6 (IL-6) were measured. In our study, not only the distribution of HDL subclasses, but also HDL-related structural proteins changed with the deterioration of metabolic disease. Moreover, lymphocytes and inflammation factors significantly gradually increased. The level of HDL2b was negatively associated with WBC, lymphocytes and hs-CRP in multivariable linear regression analysis. In multinomial logistic regression analysis, high levels of HDL3 and low levels of HDL2b increased the probability of having an unfavourable metabolic unhealth/obesity status. We supposed that HDL2b particles may play anti-inflammation by negatively regulating lymphocytes activation. HDL2b may be a therapeutic target for future metabolic disease due to the anti-inflammatory effects.

Tissue Inhibitor of Matrix Metalloproteinase 2-Loaded Polylactic Acid-Polyethylene Glycol Nanoparticles Directly Regulates Renal Tubular Epithelial Cell Proliferation via Protein Tyrosine Kinase KIT.

TIMP2 has been previously reported to be associated with acute kidney injury (AKI); however, the underlying mechanism remains unclear. Therefore, the present study investigated the regulation of TIMP2 in human tubular epithelial cells HK-2 cells. Proliferation of HK-2 cells treated by TIMP2 at normal expression level was detected. GST pulldown and mass spectrometry were performed to investigate the interacting protein of TIMP2 and immunofluorescence test was used to determine the location of the protein in HK-2 cells. Cell viability as well as the expression level of CCND1, C-FOS, MAPK1 and P-MAPK1 were detected in the samples treated by overexpressed TIMP2 and the inhibitor of the interacting protein KIT. TIMP2 significantly inhibited cell proliferation compared with the control and BB-94-treated groups (P < 0.05). KIT was identified as the interacting protein of TIMP2, and was located in both the cytoplasm and membrane of HK-2 cells. Inhibited KIT and the overexpressed of TIMP2 both significantly suppressed cell proliferation and decreased the expression levels of CCND1, MAPK1, and P-MAPK1 compared with the control (P < 0.05). No significant difference was observed in cell proliferation and the expression level of aforementioned proteins between overexpressed TIMP2 and KIT-inhibited group. The results revealed that TIMP2 regulates cell proliferation by reducing the expression levels of CCND1, MAPK1, and P-MAPK1 via KIT, indicating that TIMP2 directly regulates cell proliferation without inhibiting matrix metalloproteinases in AKI. Furthermore, PLA-PEG nanoparticles successfully transported TIMP2 to the target with no significant effect on cell proliferation.