Astragaloside â £ negatively regulates Gpr97-TPL2 signaling to protect against hyperhomocysteine-exacerbated sepsis associated acute kidney injury.

BACKGROUND: Hyperhomocysteine (HHcy) plays an important role in promoting inflammation and cell death of tubular epithelial cells. However, the role of HHcy and Astragaloside IV (AS-IV) in sepsis associated acute kidney injury (S-AKI) remain unclear. PURPOSE: A significant aspect of this study aimed to elucidate the effect of AS-Ⅳ treatment on HHcy-exacerbated S-AKI and reveal its potential mechanism. METHODS: Male C57BL/6 J mice fed with specific diet containing 2% methionine were established as in vivo models, and AS-Ⅳ was orally administrated continuously for 3 weeks, and then LPS (10 mg·kg-1 bodyweight) was given by a single intraperitoneal injection. The renal morphological changes were evaluated by HE and PAS staining. RNA-sequencing analysis was applied to select key signaling. The NRK-52E cells exposed to Hcy or combined with LPS were used as in vitro models. The mRNA and protein expression levels of Gpr97-TPL2 signaling were examined by qRT-PCR and western blotting assays. RESULTS: In vivo, HHcy mice developed more severe renal injury and prevalent tubular inflammation after LPS injection. In vitro, the levels of NGAL, Gpr97 and TPL2 were significantly increased in NRK-52E cells induced by Hcy (1.6 mM) or in combination with LPS. Notably, the effects of Hcy on TPL2 signaling was abolished by transfecting TPL2 siRNA or treating TPL2 inhibitor, without alterations in Gpr97. However, the enhancement of Gpr97-TPL2 signaling induced by Hcy was counteracted by Gpr97 siRNA. Subsequently, our findings demonstrated that AS-Ⅳ treatment can improve renal function in HHcy-exacerbated S-AKI mice. Mechanistically, AS-Ⅳ alleviated renal tubular damage characterized by abnormal increases in KIM-1, NGAL, TPL2, Gpr97, Sema3A and TNF-α, and decreases in survivin in vivo and in vitro mainly through suppressing the activation of Gpr97-TPL2 signaling. CONCLUSION: The present study suggested that HHcy-exacerbated S-AKI was mediated mechanically by activation of Gpr97-TPL2 signaling for the first time. Furthermore, our research also illustrated that AS-Ⅳ protected against HHcy-exacerbated S-AKI by attenuating renal tubular epithelial cells damage through negatively regulating Gpr97-TPL2 signaling, proposing a natural product treatment strategy for HHcy-exacerbated S-AKI.

Quality and microbial diversity of homemade bread packaged in cinnamaldehyde loaded poly(lactic acid)/konjac glucomannan/wheat gluten bilayer film during storage.

The current study aimed to reveal the changes in quality and microbial diversity of bread at 25 °C, and to analyze the activity of antifungal bilayer film on maintaining the quality of bread during 10 days of storage. Antifungal bilayer film prepared with cinnamaldehyde loaded polylactic acid/konjac glucomannan/wheat gluten (PLA/KGM/WG-CIN) was used to preserve bread samples fermented at different times. The changes in the morphology, moisture state, texture properties and microbiological analysis of bread were investigated during the storage. Analysis of microbial diversity of bread samples showed a clear decrease in the abundance of the main spoilage fungi (Aspergillus and Penicillium) in samples packed with PLA/KGM/WG-CIN film. The PLA/KGM/WG-CIN film effectively prevented moisture from evaporation, maintained the texture properties, retarded the growth of fungi, and reduced the fungi diversity during the storage. Results suggest a large potential of PLA/KGM/WG-CIN film to ensure the quality and safety of bread products.

Suppression Characteristics and Mechanism of Molasses Solution on Coal Dust: A Low-Cost and Environment-Friendly Suppression Method in Coal Mines.

Coal dust pollution poses a serious public health threat. This study aimed to investigate the feasibility of creating a coal dust suppressant using molasses, a byproduct of the sugar industry. We studied the effects of a molasses solution of varying concentrations (i.e., ranging from 0% (pure water) to 40%) on the moisture, bonding, and wind erosion properties of coal dust. Overall, the effectiveness of the molasses increased with their concentration, and it manifested itself in the following way: (1) the molasses improved the anti-evaporation ability of wet coal dust. For example, the evaporation mass of the coal dust wetted using a molasses solution decreased by 82.8%; (2) molasses effectively agglutinated coal dust; (3) molasses can effectively decrease the surface tension and increase the viscosity of the wetting solution. The surface tension of the molasses solution reached 41.37 mN/m and the viscosity increased to 6.79 mPa·s; (4) molasses can significantly suppress the wind erosion of deposited coal dust, with its wind erosion mass decreasing 99.1%; finally, (5) the effectiveness of molasses at suppressing coal dust was discussed at a molecular level. This study highlights the feasibility of a low-cost and environment-friendly dust suppressant in coal mines.

Ginsenoside Compound K Ameliorates Development of Diabetic Kidney Disease through Inhibiting TLR4 Activation Induced by Microbially Produced Imidazole Propionate.

Diabetic kidney disease (DKD) is a common and devastating complication in diabetic patients, which is recognized as a large and growing problem leading to end-stage kidney disease. As dietary-mediated therapies are gradually becoming more acceptable to patients with DKD, we planned to find active compounds on preventing DKD progression from dietary material. The present paper reports the renoprotective properties and underlying mechanisms of ginsenoside compound K (CK), a major metabolite in serum after oral administration of ginseng. CK supplementation for 16 weeks could improve urine microalbumin, the ratio of urinary albumin/creatinine and renal morphological abnormal changes in db/db mice. In addition, CK supplementation reshaped the gut microbiota by decreasing the contents of Bacteroides and Paraprevotella and increasing the contents of Lactobacillu and Akkermansia at the genus level, as well as reduced histidine-derived microbial metabolite imidazole propionate (IMP) in the serum. We first found that IMP played a significant role in the progression of DKD through activating toll-like receptor 4 (TLR4). We also confirmed CK supplementation can down-regulate IMP-induced protein expression of the TLR4 signaling pathway in vivo and in vitro. This study suggests that dietary CK could offer a better health benefit in the early intervention of DKD. From a nutrition perspective, CK or dietary material containing CK can possibly be developed as new adjuvant therapy products for DKD.

Preservation of soy protein-based meat analogues by using PLA/PBAT antimicrobial packaging film.

This study aimed to reveal the quality changes of soy protein-based meat analogues at 4 °C, and to investigate the efficacy of antimicrobial packaging on maintaining the qualities of meat analogues during 10 days of storage. Cinnamaldehyde (CI) or tea polyphenols (TP) were incorporated in polylactic acid (PLA), polybutylene adipate (PBAT) and starch blends by extrusion technique to prepare antimicrobial packaging. The changes of meat analogues were characterized for morphology, water distribution, texture properties and microbiological analysis during 10 days of storage. Cinnamaldehyde loaded PLA/PBAT film effective retarded the growth of Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) at 4 °C, giving an average reduction of E. coli and S. aureus of 3.6 and 4.1 log CFU/g on day 10, respectively. Results suggest that PLA/PBAT-CI film successfully prevents moisture from evaporation, maintains the texture properties and ensures the quality and safety of meat analogues.

Metabolic Homeostasis of Amino Acids and Diabetic Kidney Disease.

Diabetic kidney disease (DKD) occurs in 25-40% of patients with diabetes. Individuals with DKD are at a significant risk of progression to end-stage kidney disease morbidity and mortality. At present, although renal function-decline can be retarded by intensive glucose lowering and strict blood pressure control, these current treatments have shown no beneficial impact on preventing progression to kidney failure. Recently, in addition to control of blood sugar and pressure, a dietary approach has been recommended for management of DKD. Amino acids (AAs) are both biomarkers and causal factors of DKD progression. AA homeostasis contributes to renal hemodynamic response and glomerular hyperfiltration alteration in diabetic patients. This review discusses the links between progressive kidney dysfunction and the metabolic homeostasis of histidine, tryptophan, methionine, glutamine, tyrosine, and branched-chain AAs. In addition, we emphasize the regulation effects of special metabolites on DKD progression, with a focus on causality and potential mechanisms. This paper may offer an optimized protein diet strategy with concomitant management of AA homeostasis to reduce the risks of DKD in a setting of hyperglycemia.

Fucoidan mitigated diabetic nephropathy through the downregulation of PKC and modulation of NF-κB signaling pathway: in vitro and in vivo investigations.

The persistence of hyperglycemia and oxidative stress in diabetic patients ultimately leads to diabetic nephropathy (DN). In this study, we investigated the effect of sulfated polysaccharides (SPS) extracted from Laminaria japonica in relieving DN symptoms. To induce the diabetic model, normal rats were kept on a high-sugar, high-fat diet, then they were injected with streptozocin. Groups of these rats were later treated with SPS and/or protein kinase C (PKC) inhibitor. The analyses performed herein demonstrate that although diabetes significantly decreases the body weights of rats, SPS and inhibitor treatments increase these weights, as well as the ratios of renal to total body weight. Serum biochemical analyses indicate that blood urea nitrogen and serum creatinine levels gradually decrease in the SPS group. In addition, DN symptoms are substantially relieved by SPS and/or inhibitor treatments, as evidenced by histopathological analyses. Changes in the expressions of PKC-α, PKC-ß, P-selectin, nuclear factor kappa B (NF-κB), and p65, detected by immunohistochemistry and western blot assessments, show that SPS regulates diabetic nephropathy via the PKC/NF-κB pathway.

Arctium lappa L. polysaccharide can regulate lipid metabolism in type 2 diabetic rats through the SREBP-1/SCD-1 axis.

In the analysis of risk factors of diabetes mellitus with coronary heart disease, dyslipidemia is the most important. Previous studies have found that Arctium lappa L. polysaccharide (ALP) can regulate lipid metabolism in type 1 diabetic rats, but it has not been studied in type 2 diabetes. In this study, the regulatory effect of ALP on lipid metabolism in type 2 diabetic rats was investigated by constructing a model of type 2 diabetes. The results of blood biochemical analysis showed that ALP effectively reduced the synthesis of triglycerides and cholesterol, and reduced the risk of atherosclerosis in diabetic rats. Histopathological observation (hematoxylin and eosin, Masson, Periodic Acid-Schiff and oil red O staining) showed that it also effectively regulated lipid metabolism in the liver of diabetic rats and inhibited the process of liver fibrosis. Immunohistochemistry and Western blot analysis showed that ALP regulated the expression of sterol regulatory element-binding protein-1 (SREBP-1) and stearoyl-CoA desaturase 1 (SCD-1) in the liver of diabetic rats. In conclusion, the results of this study demonstrate that ALP can effectively regulate lipid metabolism and reduce the risk of atherosclerosis in type 2 diabetic rats through the SREBP-1/SCD-1 axis.