Systemic immune-inflammation Index is associated with chronic kidney disease in the U.S. population: insights from NHANES 2007-2018.

Objectives: The systemic immune-inflammation index (SII), a novel and systematic inflammatory biomarker that is associated with chronic kidney disease (CKD), has not received much attention. This study aimed to investigate the relationship between SII and CKD in the United States (U.S.) population. Methods: Our study ultimately included a nationally representative sample of 10,787 adults who participated in the 2007-2018 National Health and Nutrition Examination Survey. Weighted multivariate logistic regression was used to assess the correlation between SII and CKD, and a restricted cubic spline (RCS) model was subsequently used to explore the non-linear relationship between SII and CKD. Subgroup analyses were performed to further the effects of other covariates on the relationship between SII and CKD. Results: Following confounder adjustment, a higher SII was related to the incidence of CKD (OR =1.36; 95% CI, 1.07-1.73; p =0.01), as validated by multivariable logistic regression. The RCS curve revealed a non-linear positive correlation between SII/1000 and CKD incidence (p for non-linear =0.0206). Additionally, subgroup analysis confirmed a stronger correlation for male participants (OR =2.628; 95% CI, 1.829-3.776) than for female participants (OR =1.733; 95% CI, 1.379-2.178) (p for interaction =0.046). Conclusions: SII is positively associated with the incidence of CKD among U.S. adults, especially in males. However, further studies are needed to confirm our findings and explore the causal factors that can contribute to the prevention and treatment of CKD.

Mast cells in colorectal cancer tumour progression, angiogenesis, and lymphangiogenesis.

The characteristics of the tumour cells, as well as how tumour cells interact with their surroundings, affect the prognosis of cancer patients. The resident cells in the tumour microenvironment are mast cells (MCs), which are known for their functions in allergic responses, but their functions in the cancer milieu have been hotly contested. Several studies have revealed a link between MCs and the development of tumours. Mast cell proliferation in colorectal cancer (CRC) is correlated with angiogenesis, the number of lymph nodes to which the malignancy has spread, and patient prognosis. By releasing angiogenic factors (VEGF-A, CXCL 8, MMP-9, etc.) and lymphangiogenic factors (VEGF-C, VEGF-D, etc.) stored in granules, mast cells play a significant role in the development of CRC. On the other hand, MCs can actively encourage tumour development via pathways including the c-kit/SCF-dependent signaling cascade and histamine production. The impact of MC-derived mediators on tumour growth, the prognostic importance of MCs in patients with various stages of colorectal cancer, and crosstalk between MCs and CRC cells in the tumour microenvironment are discussed in this article. We acknowledge the need for a deeper comprehension of the function of MCs in CRC and the possibility that targeting MCs might be a useful therapeutic approach in the future.

Enhanced Electrochemical O2 -to-H2 O2 Synthesis Via Cu-Pb Synergistic Interplay.

Electrocatalytic reduction of oxygen (O2 ) to produce hydrogen peroxide (H2 O2 ) frequently suffers from the low activity and poor selectivity of catalysts owing to the lack of systematic strategies. The resulting enhancement to enable the further design of a new bimetallic catalyst with the synergistic interplay, as exemplified by Cu-Pb catalyst for two-electron oxygen reduction reaction (2e- ORR), is reported here. Critically, in-depth evidence, including density functional theory (DFT) calculations, electrochemical signals, in-situ Raman, and H2 O2 -proof work, allude to a catalytic favor to the 2e- ORR of Cu-Pb.

Role of salt inducible kinase 1 in high glucose-induced lipid accumulation in HepG2 cells and metformin intervention.

AIMS: To investigate the roles of salt inducible kinase (SIK1) in high glucose-induced triglyceride accumulation in human hepatoma HepG2 cells as well as in the molecular mechanism by which metformin, a drug to treat diabetes, suppresses high glucose-induced lipogenesis. MAIN METHODS: A cell model for high glucose-induced hepatic steatosis was prepared by exposing HepG2 cells to high glucose (25mmol) in the absence or presence of metformin (0.5mmol). Intracellular triglycerides were visualized by Oil Red O and measured using a triglyceride assay kit. Cell viability was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method. SIK1 overexpression in HepG2 cells was achieved by transient transfection, and the mRNA and protein levels of SIK1 and lipogenic factors were measured using a reverse transcription-polymerase chain reaction and western blotting, respectively. KEY FINDINGS: Lipid accumulation in HepG2 cells was obvious after treatment with high glucose for 24h. In response to high glucose, SIK1 expression was negatively correlated with that of lipogenic factors and lipid accumulation in HepG2 cells. We observed that overexpression of SIK1, or treatment with metformin, suppressed lipogenesis, even in high glucose conditions. Furthermore, treatment with metformin upregulated SIK1 mRNA and protein levels, as well as the active form of SIK1. SIGNIFICANCE: SIK1 plays a vital role in high glucose-induced lipid accumulation, and metformin suppresses lipogenesis via the induction and activation of SIK1.

Calycosin attenuates osteoporosis and regulates the expression of OPG/RANKL in ovariectomized rats via MAPK signaling.

We aimed at exploring the effect of calycosin (CA) on osteoporosis in ovariectomized (OVX) rats. Sprague-Dawley (SD) rats were divided into five groups: Sham group, OVX group, OVX group treated with estradiol valerate (EV), CAL group treated with 15 mg/kg/d of CA and CAH group treated with 30 mg/kg/d of CA for 12 weeks. Bone mineral density (BMD), histopathology, body weight, parameters in serum and urine were observed. Gene expression and protein level of OPG/RANKL were also studied by real-time PCR and western blot, respectively. We further identified the effect of CA on mitogen-activated protein kinase (MAPK) signaling. In comparison with OVX rats, CAL and CAH significantly increased the BMD by 8.3% and 19.0%. Treatment with CA notably inhibited the excretion of Ca, P and Cr. CAH also significantly increased the level of alkaline phosphatase (ALP) and decreased the level of tartrate-resistant acid phosphatase (TRAP) in serum of OVX rats. CA could improve the trabecular bone area, and increased the trabecular number and the trabecular connection after 12-week. CA also increased the expression of osteoprotegerin (OPG) and decreased the Receptor Activator for Nuclear Factor-κB Ligand (RANKL) mRNA expression compared with the OVX rats. In addition, CA could effectively decrease the phosphorylation of MAPKs induced by ovariectomy. In conclusion, CA had remarkable antiosteoporotic activity and therefore can be a promising candidate for the treatment of postmenopausal osteoporosis.

Zhenqing recipe improves glucose metabolism and insulin sensitivity by repressing hepatic FOXO1 in type 2 diabetic rats.

Forkhead box O1 (FOXO1) plays an important role in glucose metabolism at the gene transcription level. Increased FOXO1 activity results in hyperglycemia by promoting the expression of gluconeogenic enzymes such as phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase), and inhibiting glucokinase (GK). This study evaluates the effect of Zhenqing Recipe (ZQR), a Chinese herbal medicine, on hyperglycemia and its molecular mechanisms. Type 2 diabetic rats, developed by high-fat diet combined with low-dose STZ injections, were randomly divided into untreated diabetic, ZQR and metformin group. Normal rats served as control. After an eight-week treatment, fasting blood glucose was significantly decreased and insulin sensitivity index was obviously increased in the ZQR group. ZQR also improved the oral glucose tolerance. Compared with the control group, the mRNA levels of PEPCK and G6Pase were significantly elevated, while GK mRNA expression was decreased in the liver of untreated diabetic rats. ZQR significantly reduced the mRNA levels of PEPCK and G6Pase, and increased GK mRNA expression. The hepatic mRNA and protein expression of FOXO1 in the untreated diabetic group was markedly increased compared to controls. The administration of ZQR significantly decreased the mRNA and protein levels of hepatic FOXO1. The data suggest that ZQR improves glucose metabolism and insulin sensitivity, which is accompanied with regulating mRNA expression of GK and gluconeogenic genes. This anti-diabetic effect of ZQR is due to its ability to repress hepatic FOXO1 at the mRNA and protein level.

Zhenqing recipe alleviates diabetic nephropathy in experimental type 2 diabetic rats through suppression of SREBP-1c.

ETHNOPHARMACOLOGICAL RELEVANCE: Zhenqing Recipe (ZQR), a Chinese herbal prescription, is used to improve renal function of patients with diabetic nephropathy. In current research, the therapeutic effects of ZQR on type 2 diabetic nephropathy and the underlying molecular mechanisms were explored. MATERIALS AND METHODS: Animal model with diabetic nephropathy was developed by high fat/sucrose diet feeding plus streptozotocin injection for 4 weeks. The diabetic rats were then orally administered with ZQR extract at the dose of 4 g/kg, 8 g/kg body weight/day for 8 weeks. RESULTS: Serum glucose, triglyceride and total cholesterol in untreated diabetic rats were significantly higher than that of normal control rats. ZQR treatment not only reduced serum glucose level in diabetic rats, but also decreased serum triglyceride and total cholesterol in a dose-dependent manner. Urinary albumin excretion rate, serum urea and creatinine were significantly decreased in ZQR groups compared with untreated diabetic group. Histopathological study of kidney samples showed that extracellular mesangial matrix expansion in diabetic rats was suppressed by ZQR treatment. Both mRNA and protein levels of sterol regulatory element binding-protein-1c (SREBP-1c), and its target genes including acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS) in renal cortex were significantly decreased in ZQR treated rats compared to untreated diabetic rats. Consequently, renal triglyceride was significantly reduced in ZQR groups. Furthermore, ZQR significantly inhibited the overexpression of transforming growth factor-ß1 and fibronectin in the renal cortex of diabetic rats. CONCLUSIONS: Oral treatment of ZQR improved diabetic nephropathy by inhibiting the overexpression of SREBP-1c and its target genes including ACC and FAS in experimental type 2 diabetic rats.

Effects of caloric restriction on SIRT1 expression and apoptosis of islet beta cells in type 2 diabetic rats.

Increasing evidence suggests that a restricted caloric intake extends the life span of mammals, and SIRT1 may play a key role in this process. To study the effects of caloric restriction on SIRT1 expression and apoptosis of islet beta cells in type 2 diabetic rats, we first induced a model of type 2 diabetes in rats with a low-dose of streptozotocin. Then, the rats were fed with a normal diet, high-fat diet or 60% caloric restriction, respectively. As a result, the apoptosis ratio of islet beta cells in diabetic rats was dramatically increased compared to the control group, and mRNA and protein expression of SIRT1 in islet beta cells were much lower than those of the control group. After caloric restriction for 1 month, the blood glucose and serum insulin of rats decreased. The mRNA and protein expression of SIRT1 in islet beta cells significantly increased; however, the apoptosis ratio of islet beta cells decreased remarkably. These data show that caloric restriction notably improves the sensitivity to insulin and significantly increases mRNA and protein expression of SIRT1 while decreasing the apoptosis ratio of islet beta cells in diabetic rats. Therefore, SIRT1 may play an important role in the apoptosis of islet beta cells of type 2 diabetes.

[Effects of calorie restriction on SIRT1 expression in liver of nonalcoholic fatty liver disease: experiment with rats].

OBJECTIVE: To investigate the molecular mechanisms of calorie restriction (CR) in treatment of nonalcoholic fatty liver disease (NAFLD). METHODS: 25 male Wistar rats were randomly divided into 2 groups: normal control group (NC, n = 7) fed with regular diet and high fat diet-NAFLD model group (HFM, n = 18) fed with high-fat diet. Two months later, the rats in Group HFM were further divided into 2 subgroups: continuous high-fat feeding group (HF, n = 9) and normal diet feeding with 60% calorie restriction group (CR, n = 9). The rats were sacrificed after 1 month calorie restriction. By the end of experiment, body weight (BW), visceral fat mass (VF), fasting plasma glucose (FPG), fasting serum insulin (FINS), blood lipids (BL), including total cholesterol (TC) and triglyceride (TG), and hepatoultrastructure changes were examined to evaluate the effect of different feeding protocols on the experimental animals. The mRNA expression of the longevity gene SIRT1 in the liver was detected by RT-PCR. Western blot analysis was performed to determine the expression of SIRT1 protein in each group. RESULTS: Electron microscopy showed that the rats in group HF displayed obviously abnormal hepatoultrastructure, and the ultramicropathology changes of liver cell were improved obviously in Group CR. The VF, FINS, FPG, TC, and TG of the Group HF were 15.1 g +/- 4.1 g, 29.22 mU/L +/- 7.28 mU/L, 6.2 mmol/L +/- 1.46 mmol/L, 2.61 mmol/L +/- 0.29 mmol/L, and 1.35 mmol/L +/- 0.21 mmol/L respectively, all significantly higher than those in Group NC (9.0 g +/- 0.4 g, 13.09 mU/L +/- 1.18 mU/L, 4.4 mmol/L +/- 0.57 mmol/L, 1.41 mmol/L +/- 0.28 mmol/L, and 0.67 mmol/L +/- 0.10 mmol/L respectively, all P < 0.01). The mRNA expression of SIRT1 in the liver of Group HF was significantly lower than that of Group NC (P < 0.05), and the mRNA expression of SIRT1 in the liver of Group CR was significantly higher than those of Group HF and Group NC (both P < 0.01). The protein expression of SIRT1 of Group HF was significantly lower than that of Group NC (P < 0.01), and that of Group CR was significantly higher than that of Group HF, however, still significantly lower than that of Group NC (both P < 0.01). The BW and VF, FINS, FPG, TC, and TG of Group CR were all significantly lower than those of Group HF (all P < 0.01). CONCLUSION: CR can reverse NAFLD significantly. The increased expression of SIRT1 in liver induced by CR may be an important molecular mechanism involved in the improvement of NAFLD by CR.

The expression of SIRT1 in nonalcoholic fatty liver disease induced by high-fat diet in rats.

OBJECTIVE: SIRT1 is an NAD(+)-dependent deacetylase and its enzymatic activity may be regulated by cellular energy. SIRT1 overexpression reduces the level of oxygen consumption, which is correlative with nonalcoholic fatty liver disease (NAFLD). To elucidate the role of SIRT1 on the development of NAFLD, we investigated the expression of SIRT1 in NAFLD induced by high-fat diet in rats and the effects of calorie restriction. METHODS: Thirty-one male Wistar rats were divided at random into four groups. The rats in the normal control group NC (n=7) and in the NAFLD model group HF (n=9) were fed ad libitum with normal chow and high-fat diet, respectively, for 3 months, the rats in the calorie restriction (CR) group HCR (n=9) were fed with a high-fat diet for 2 months and then 60% CR with normal chow for 1 month, and the rats in group CRH (n=6) were firstly fed with 60% CR with normal chow for 1 month and then fed a high-fat diet for 2 months. At the end of the experiment, some parameters and expressions of SIRT1 were detected. RESULTS: The rats in group HF displayed NAFLD. Compared with group NC, the expression of SIRT1 protein was significantly decreased (P<0.01). However, the lower body weight and visceral fat mass of rats in group HCR were showed. Compared with group HF, CR increased the expression of SIRT1 in liver significantly (P<0.01). Consequently, the ultramicropathology changes of NAFLD prominently improved in this group. Meanwhile, the rats in group CRH displayed higher expression of SIRT1 protein and very gentle pathology changes of NAFLD. CONCLUSION: The expression of SIRT1 is reduced significantly in NAFLD induced by high-fat diet in rats. CR increase-SIRT1 protein expression may be an important mechanism by which CR improves NAFLD.

Decreased infiltration of macrophages and inhibited activation of nuclear factor-kappa B in blood vessels: a possible mechanism for the anti-atherogenic effects of losartan.

UNLABELLED: Short-term administration of losartan reduced the aortic surface lesion area and mean intimal thickness. The mechanisms for reducing atherosclerotic progression by losartan may be related to decreased macrophage proliferation and accumulation in the arterial wall, decreased activation of nuclear factor-kappa B and expression of its target gene ICAM-I. OBJECTIVE: Recent studies suggest that angiotensin II (Ang II) may contribute to the vascular inflammatory response and atherosclerosis. Losartan is a specific AT1 receptor antagonist which can effectively inhibit the effects of Ang II. However, the effects of losartan on atherogenesis have been rarely demonstrated. We designed this study to investigate the effects of short-term administration of losartan on atherosclerotic lesions in the aorta from rabbits fed a cholesterol-enriched diet and the possible mechanisms of its anti-atherogenic effects. METHODS AND RESULTS: The rabbits were randomly divided into three groups: (a) cholesterol group; (b) losartan-treated group; (c) normal control group. We observed that mean serum lipid levels in the cholesterol group were significantly higher than those in normal control rabbits, while blood pressure between two groups did not change significantly. Treatment with losartan did not affect serum lipid levels or systolic blood pressure but did reduce the aortic surface lesion area and mean intimal thickness. The number of macrophages markedly decreased after administration of losartan. Losartan also attenuated the activation of nuclear factor-kappa B and the expression of its target gene ICAM-I. CONCLUSIONS: In summary, losartan inhibited atherosclerotic progression by decreasing macrophage proliferation and accumulation in the arterial wall. The mechanisms for reducing atherosclerotic progression by losartan may be related to decreased activation of nuclear factor-kappa B.