Protective Effects of 2-Dodecyl-6-Methoxycyclohexa-2,5 -Diene-1,4-Dione Isolated from Averrhoa Carambola L. (Oxalidaceae) Roots on Neuron Apoptosis and Memory Deficits in Alzheimer's Disease.

BACKGROUND/AIMS: The roots of Averrhoa carambola L. (Oxalidaceae) have long been used as a traditional Chinese medicine for the treatment of headaches, vomiting, coughing and hangovers. 2-dodecyl-6-methoxycyclohexa-2, 5-1, 4-dione (DMDD) has been isolated from A. carambola L. roots, and this study was carried out to investigate the potential beneficial effects of DMDD on neuron apoptosis and memory deficits in Alzheimer's disease. METHODS: The effects of a DMDD on learning and memory in APP/PS1 transgenic AD mice in vivo were investigated via Morris water maze and Y-type electric maze tests. In vitro, Cell viability was assessed by CCK-8. Apoptosis was assessed by Annexin V-FITC/PI flow cytometry assay, and transmission electron microscopy assay. Relative quantitative real-time PCR and Western blot were used to determine the expressions of genes and proteins. RESULTS: The spatial learning and memory deficit, fear memory deficit, as well as apoptosis and loss of neuron in hippocampal area of APP/PS1 mice were reversed by DMDD in APP/PS1 transgenic AD mice. DMDD protected against the Aß1-42-induced apoptosis, loss of mitochondria membrane potential, induction of pro-apoptotic Bcl-2 family protein Bax, reduction of anti-apoptotic Bcl-2 family proteins Bcl-2, and activation of Caspase-3, and -9 in PC-12 cells. The Bcl-2/Bax ratio was also increased in DMDD-pretreated PC-12 cells in vitro and APP/PS1 mice in vivo. CONCLUSION: DMDD has potential benefit on treating learning and memory deficit in APP/PS1 transgenic AD mice, and its effects may be associated with reversing the apoptosis of neuron via inhibiting Bax/Bcl-2 mediated mitochondrial membrane potential loss.

Effect of Yulangsan Polysaccharide on the Reinstatement of Morphine-Induced Conditioned Place Preference in Sprague-Dawley Rats.

We previously reported that Yulangsan polysaccharide (YLSP), which was isolated from the root of Millettia pulchra Kurz, attenuates withdrawal symptoms of morphine dependence by regulating the nitric oxide pathway and modulating monoaminergic neurotransmitters. In this study, we investigated the effects and mechanism of YLSP on the reinstatement of morphine-induced conditioned place preference (CPP) in rats. A CPP procedure was employed to assess the behavior of rats, and indicators of serum and four brain regions (nucleus accumbens, ventral tegmental area, hippocampus and prefrontal cortex) were determined to explore its underlying mechanism. YLSP inhibited priming morphine-induced reinstatement of CPP in a dose-dependent manner. YLSP markedly reduced nitric oxide and nitric oxide synthase levels in the brain. Moreover, YLSP significantly decreased the dopamine and norepinephrine levels in the serum and brain. Furthermore, YLSP significantly decreased cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) concentrations, inhibited the expression of dopamine D1 receptors and cAMP response element binding protein mRNA, and improved the expression of dopamine D2 receptor mRNA in the four brain regions. Our findings indicated that YLSP could inhibit the reinstatement of morphine-induced CPP possibly by modulating the NO-cGMP and D1R-cAMP signaling pathways.

Dengue virus and Japanese encephalitis virus infection of the central nervous system share similar profiles of cytokine accumulation in cerebrospinal fluid.

Dengue virus (DENV) and Japanese encephalitis virus (JEV) are two important pathogenic viruses that can cause severe encephalitis, which is accompanied by inflammatory cytokines. However, the inflammatory cytokine content of cerebrospinal fluid (CSF) in DENV and JEV infection of central nervous system are not sufficiently studied. To investigate cytokine levels in serum and CSF of hospitalised children with DENV and JEV infection of the central nervous system, a total of 183 hospitalised children with viral encephalitis-like syndrome were enrolled between May 2014 and April 2015 at the Children's Hospital of Chenzhou, Hunan, China. DENV and JEV infection was diagnosed by ELISA. Cytokine levels in the serum and CSF were measured by commercial ELISA kits. Twenty-nine (15.85%) and 26 (14.21%) DENV and JEV infections were detected in 183 patients with viral encephalitis-like syndrome, respectively. Higher granulocyte-macrophage colony-stimulating factor (GM-CSF) levels were detected in the serum of JEV infected patients than in DNEV patients (p < 0.05) or in healthy controls (p < 0.001), and levels of GM-CSF, interleukin 6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1) were higher in the CSF than serum in both DENV and JEV infection. Both DENV and JEV infection induced similar cytokine accumulation profiles in the CSF, which probably contributed to DENV- and JEV-induced immunopathogenesis.

The Antioxidant, Anti-Inflammatory and Anti-Apoptotic Activities of the Bauhinia Championii Flavone are Connected with Protection Against Myocardial Ischemia/Reperfusion Injury.

BACKGROUND/AIMS: Previous studies have demonstrated that Bauhinia championii flavone (BCF) exhibits anti-oxidative, anti-hypoxic and anti-stress properties. This study was designed to investigate whether BCF has a cardioprotective effect against myocardial ischemia/reperfusion (I/R) injuries in rats and to shed light on its possible mechanism. METHODS: The model of I/R was established by ligating the left anterior descending coronary artery for 30 min, then reperfusing for 180 min. Hemodynamic changes were continuously monitored. The content of malondialdehyde (MDA) as well as the lactate dehydrogenase (LDH), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities were assessed. The release of interleukin-6 (IL-6) was measured by enzyme-linked immunosorbent assay (ELISA). Apoptosis of cardiomyocytes was determined by caspase-3 activity and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. The expression of TLR4, NF-x03BA;Bp65, Bcl-2 and Bax were detected by western blotting. RESULTS: Pretreatment with BCF significantly reduced the serum levels of LDH, MDA and IL-6, but increased the activities of SOD and GSH-Px. It also attenuated myocardial infarct size, reduced the apoptosis rate and preserved cardiac function. Furthermore, BCF inhibited caspase-3 activity and the expression of TLR4, phosphorylated NF-x03BA;Bp65 and Bax, but enhanced the expression of Bcl-2. CONCLUSION: These results provide substantial evidence that BCF exerts a protective effect on myocardial I/R injury, which may be attributed to attenuating lipid peroxidation, the inflammatory response and apoptosis.

Anti-Tumor Effects of the Polysaccharide Isolated from Tarphochlamys Affinis in H22 Tumor-Bearing Mice.

BACKGROUND: The previous studies have demonstrated that the polysaccharide isolated from Tarphochlamys affinis (PTA) exhibits anti-tumor effect on S180 tumor-bearing mice and protective effects against hepatic injury. METHODS: In this study, we investigated the anti-tumor activity and possible underlying mechanism of PTA on liver cancer using a murine H22 hepatocarcinoma model. RESULTS: PTA was capable of repressing transplanted H22 solid hepatic tumor cell growth in vivo. The relative weight of immune organs (spleen and thymus) and lymphocyte proliferation induced by ConA or LPS were improved after PTA treatment. Furthermore, treatment with PTA promoted immune-stimulating serum cytokine secretion in H22 tumor-bearing mice. Additionally, the percentage of CD4+ T lymphocytes, CD8+ T lymphocytes and NK cells was increased in tumor-bearing mice following PTA administration. In tumor tissue, PTA significantly up-regulated the expression of Bax and p53 proteins and down-regulated the expression of Bcl-2 protein. In addition, at the therapeutic dose, PTA displayed very few toxic effects to major organs, such as the liver and kidney, in tumor-bearing mice. CONCLUSION: In H22 tumor-bearing mice, PTA exhibited prominent anti-tumor activity in vivo. The possible mechanism of action might be related to enhanced host immune system function and induction of H22 tumor cell apoptosis.

Protective Effects of 2-Dodecyl-6-Methoxycyclohexa-2,5 -Diene-1,4-Dione Isolated from Averrhoa Carambola L. (Oxalidaceae) Roots on High-Fat Diet-Induced Obesity and Insulin Resistance in Mice.

BACKGROUND/AIMS: The roots of Averrhoa carambola L. (Oxalidaceae) have long been used as a traditional Chinese medicine for the treatment of diabetes and diabetes-related diseases. 2-dodecyl-6-methoxycycyclohexa-2,5-1,4-dione (DMDD) has been isolated from A. carambola L. roots, and this study was carried out to investigate the potential beneficial effects of DMDD on obesity and insulin resistance induced by a high-fat diet (HFD) in mice. METHODS: C57BL/6J mice were fed a HFD for 16 weeks and orally administered DMDD (12.5, 25, or 50 mg/kg of body weight per day) and metformin (280 mg/kg of body weight per day) for the last 4 weeks. RESULTS: The body weights and adipose tissue weights as well as the serum levels of blood glucose, total cholesterol, triglycerides, free fatty acids, insulin, interleukin-6, and tumor necrosis factor-α were significantly decreased by DMDD, and the expression of Toll-like receptor 4 (TLR4) and myeloid differentiation factor (Myd88) in the epididymal adipose tissue was downregulated by DMDD. In contrast, insulin sensitivity was enhanced. The results of the glucose tolerance tests, insulin tolerance tests, and insulin release tests indicated that there was a marked improvement in insulin secretion, and the areas under the curve corresponding to the three tests were also significantly decreased by DMDD. The activities of superoxide dismutase and glutathione peroxidase were simultaneously enhanced, whereas the content of malondialdehyde was decreased by DMDD in the liver homogenates of the C57BL/6J mice. In addition, hepatic steatosis and adipocyte hypertrophy, as assessed by H&E staining of liver and adipose tissues, were significantly improved by DMDD. CONCLUSION: These data suggest that MDD has potential benefits for the treatment of HFD-induced obesity and insulin resistance, and its effects may be associated with improvements in lipid metabolism and inhibition of the expression of TLR4 in adipose tissues.

Protective Effect of 2-Dodecyl-6-Methoxycyclohexa-2, 5-Diene-1, 4-Dione, Isolated from Averrhoa Carambola L., Against Palmitic Acid-Induced Inflammation and Apoptosis in Min6 Cells by Inhibiting the TLR4-MyD88-NF-κB Signaling Pathway.

BACKGROUND/AIMS: Studies have demonstrated that 2-dodecyl-6-methoxycyclohexa-2, 5-diene-1, 4-dione (DMDD), isolated from the roots of Averrhoa carambola L., has significant therapeutic potential for the treatment of diabetes. However, the protective effect of DMDD against pancreatic beta cell dysfunction has never been reported. We investigated whether DMDD protected against palmitic acid-induced dysfunction in pancreatic ß-cell line Min6 cells by attenuating the inflammatory response and apoptosis and to shed light on its possible mechanism. METHODS: Cell viability was assessed by CCK-8. Glucose-stimulated insulin secretion levels and inflammatory cytokines levels were examined by ELISA. Apoptosis was assessed by Annexin V-FITC/PI Flow cytometry assay, Hoechst 33342/PI double-staining assay, and Transmission electron microscopy assay. Relative quantitative real-time PCR and western blot were used to determine the expressions of genes and proteins. RESULTS: Cell viability and glucose-stimulated insulin secretion levels were increased in DMDD-pretreated Min6 cells. DMDD inhibited inflammatory cytokines IL-6, TNF-α and MCP-1 generations in palmitic acid (PA)-induced Min6 cells. Moreover, DMDD protected against PA-induced Min6 cells apoptosis and the expression of Cleaved-Caspase-3, -8 and -9 were down-regulated and the Bcl-2/Bax ratio was increased in DMDD-pretreated Min6 cells. In addition, the expression of TLR4, MyD88 and NF-κB were down-regulated in DMDD-pretreated Min6 cells and TAK-242-pretreated group cells. CONCLUSIONS: DMDD protected Min6 cells against PA-induced dysfunction by attenuating the inflammatory response and apoptosis, and its mechanism of this protection was associated with inhibiting the TLR4-MyD88-NF-κB signaling pathway.

Coronavirus Infections in the Central Nervous System and Respiratory Tract Show Distinct Features in Hospitalized Children.

BACKGROUND/AIMS: Coronavirus (CoV) infections induce respiratory tract illnesses and central nervous system (CNS) diseases. We aimed to explore the cytokine expression profiles in hospitalized children with CoV-CNS and CoV-respiratory tract infections. METHODS: A total of 183 and 236 hospitalized children with acute encephalitis-like syndrome and respiratory tract infection, respectively, were screened for anti-CoV IgM antibodies. The expression profiles of multiple cytokines were determined in CoV-positive patients. RESULTS: Anti-CoV IgM antibodies were detected in 22/183 (12.02%) and 26/236 (11.02%) patients with acute encephalitis-like syndrome and respiratory tract infection, respectively. Cytokine analysis revealed that the level of serum granulocyte colony-stimulating factor (G-CSF) was significantly higher in both CoV-CNS and CoV-respiratory tract infection compared with healthy controls. Additionally, the serum level of granulocyte macrophage colony-stimulating factor (GM-CSF) was significantly higher in CoV-CNS infection than in CoV-respiratory tract infection. In patients with CoV-CNS infection, the levels of IL-6, IL-8, MCP-1, and GM-CSF were significantly higher in their cerebrospinal fluid samples than in matched serum samples. CONCLUSION: To the best of our knowledge, this is the first report showing a high incidence of CoV infection in hospitalized children, especially with CNS illness. The characteristic cytokine expression profiles in CoV infection indicate the importance of host immune response in disease progression.

The Effects of 17-Methoxyl-7-Hydroxy-Benzene-Furanchalcone on Pressure Overload-Induced Cardiac Remodeling in Rats and the Endothelial Mechanisms Based on PGI2.

AIM: The primary objective of this study was to study the effects of 17-methoxyl-7-hydroxy-benzene-furanchalcone (MHBFC) on pressure overload-induced cardiac remodeling in rats, as well as the endothelial mechanisms based on PGI2. METHODS: Six weeks following surgery, rats were divided randomly into the following groups: a sham group, a model group, an MHBFC 12 mg/kg/day group (MHBFC 12), an indomethacin 2 mg/kg/day group (Indo 2), and an Indo 2+ MHBFC 12 group. The MS 4000 organism signal system was used to record the rats' hemodynamic indices. Additionally, the heart weight was determined, and the cardiac remodeling index was calculated. HE and Masson's stains were utilized to perform histological analyses; the immunofluorescence was used to observe the microvessel density of myocardial tissue; the colorimetric method was used to determine the hydroxyproline content of cardiac tissue; the ELISA method was used to measure the plasma PGI2 content; and transmission electron microscopy was used to observe the ultrastructure of the myocardium. RESULTS: A hyperdynamic circulation state, cardiac remodeling, decreased microvessel density and decreased plasma PGI2 content were each observed in the model group compared with the sham group, in which any changes in the above parameters were effectively reversed by MHBFC. Single-use Indo administration resulted in the progression of these pathophysiological changes; however, MHBFC prevented the worsening of these parameters. CONCLUSION: MHBFC significantly reverses pressure overload-induced cardiac remodeling, and its mechanism may partially contribute to the amelioration of endothelial cell function and the augmentation of PGI2 synthesis and secretion.

Protective effects of Millettia pulchra flavonoids on myocardial ischemia in vitro and in vivo.

BACKGROUND: Previous studies have demonstrated that Millettia pulchra flavonoids (MPF) exhibit protective effects on myocardial ischemia reperfusion injury (MI/RI) in isolated rat hearts and show anti-oxidative, anti-hypoxic and anti-stress properties. METHODS: In this study, the cardioprotective effects of MPF on myocardial ischemia and its underlying mechanisms were investigated by a hypoxia/ reoxygenation (H/R) injury model in vitro and a rat MI/RI model in vivo. RESULTS: We found that the lactate dehydrogenase (LDH) and inducible nitric oxide synthase (iNOS) activities were decreased in the MPF pretreatment group, whereas the activities of constructional nitric oxide synthase (cNOS), total nitric oxide synthase (tNOS), Na(+)-K(+)-ATPase and Ca(2+)-Mg(2+)-ATPase were significantly increased. In addition, the cardiocytes were denser in the MPF groups than in the control group. The mortality rate and apoptosis rate of cardiocytes were significantly decreased. Furthermore, pretreatment with MPF in vivo significantly improved the hemodynamics, decreased malondialdehyde (MDA) abundance, increased the activities of plasma superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and decreased the expression of the Bax protein and ratio Bax/Bc1-2 ration. CONCLUSIONS: These results suggest that MPF is an attractive protective substance in myocardial ischemia due to its negative effects on heart rate and ionotropy, reduction of myocardial oxidative damage and modulation of gene expression associated with apoptosis.

Effect of the Total Extract of Averrhoacarambola (Oxalidaceae) Root on the Expression Levels of TLR4 and NF-κB in Streptozotocin-Induced Diabetic Mice.

BACKGROUND: Averrhoacarambola L., which is a folk medicine used in diabetes mellitus (DM) in ancient China, has been reported to have anti-diabetic efficacy. AIMS: The aim of this study was to evaluate the hypoglycemic effect of the extract of Averrhoacarambola L. root (EACR) on the regulation of the Toll-like receptor 4 (TLR4)-Nuclear-factor kappa B (NF-κB) pathway in B) pathway in streptozotocin (STZ)-induced diabetic mice. METHODS: the mice were injected with STZ (120 mg/kg body weight) via a tail vein. After 72 h, the mice with FBG ≥ 11.1 mmol/L were confirmed as having diabetes. Subsequently, the mice were treated intragastrically with EACR (300, 600, 1200 mg/kg body weight/d) and metformin (320 mg/kg body weight/d) for 14 days. RESULTS: As a result the serum fasting blood glucose (FBG), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels were decreased following EACR administration. Immunohistochemical analysis revealed that the pancreatic tissue expression levels of TLR4 and NF-κB were downregulated after EACR administration. EACR suppressed pancreatic mRNA expression level of TLR4 and blocked the downstream NF-κB pathway in the pancreas. According to Western blot analysis EACR suppressed pancreatic TLR4 and NF-κB protein expression levels. Histopathological examination of the pancreas showed that STZ-induced pancreas lesions were alleviated by the EACR treatment. CONCLUSION: These findings suggest that the modulation of the IL-6 and TNF-α inflammatory cytokines and the suppression of the TLR4-NF-κB pathway are most likely involved in the anti-hyperglycemic effect of EACR in STZ-induced diabetic mice.

Mechanism of the protective effect of Yulangsan flavonoid on myocardial ischemia/reperfusion injury in rats.

AIMS: Effect and mechanism of Yulangsan flavonoid (YLSF) on rat myocardial ischemia/reperfusion injury (MI/RI) has been investigated. METHODS: Sprague-Dawley (SD) rats were randomly divided into seven groups (sham group, model group and NS group: 2 mL of normal saline/kg body weight was administered; diltiazem group: 5 mg of diltiazem hydrochloride/kg body weight was administered; YLSFL, YLSFM and YLSFH groups: 20, 40 and 80 mg of YLSF/kg body weight was administered) and the MI/RI model was established. Myocardial infarct area, levels of myocardial enzymes and nitric oxide synthase (NOS) were measured. Caspase-3 and adenine nucleotide translocator-1 (ANT1) mRNA expression were evaluated by reverse transcription polymerase chain reaction (RT-PCR). Pathological structure and cardiocyte ultrastructure were also analysed. RESULTS: Compared with the MI/RI group, pretreatment with YLSF or diltiazem hydrochloride decreased the infarct area, levels of inducible nitric oxide synthase (iNOS), caspase-3 as well as the leakage of myocardial enzyme and increased activities of total nitric oxide synthase (tNOS) as well as constitutive nitric oxide synthase (cNOS). Cellular edema and the infiltration of inflammatory cells were alleviated. CONCLUSIONS: The experiment showed that YLSF protected the heart against MI/RI, possibly by reducing lipid peroxidation damage, regulating NOS activity and modulating the apoptosis genes expression.

Protective effects of total extracts of Averrhoa carambola L. (Oxalidaceae) roots on streptozotocin-induced diabetic mice.

BACKGROUND: In Chinese culture, the roots of Averrhoa carambola L. have long been used for medical purposes due to their potent pharmaceutical activities, such as improving digestive function and treating diabetes. METHODS: Recently, we prepared extracts of Averrhoa carambola L. root (EACR), which were isolated from Averrhoa carambola L. roots using ethanol or water. This study was designed to investigate the potential effects of EACR on streptozotocin (STZ) diabetic mice and to explore the underlying mechanism of these effects. Male mice were injected with STZ through the tail vein (120 mg/kg body weight) and were identified as a diabetic mouse model when the level of blood glucose was ≥11.1 mmol/L. Subsequently, the mice were administered EACR (150, 300, 600, 1200 mg/kg body weight/d) and metformin (320 mg/kg body weight/d) via intragastric gavage for three weeks. RESULTS: The results indicated that EACR significantly decreased the serum levels of blood glucose, total cholesterol (TC), triglycerides (TGs) and free fatty acids (FFAs), whereas the content of serum insulin was elevated. In addition, the expressions of apoptosis-related regulators (including caspase-3, caspase-8 and caspase-9) and the apoptosis-induced protein Bax were markedly down-regulated by EACR, whereas the expression of the anti-apoptotic Bcl-2 protein was notably increased. Furthermore, EACR could protect the diabetic mice against the STZ-induced apoptosis of pancreatic ß cells. CONCLUSION: Taken together, these findings indicate that EACR plays an effective hyperglycemic role that is associated with ameliorating metabolic functions and with inhibiting apoptosis in pancreas tissue.

The effect of 17-methoxyl-7-hydroxy-benzene-furanchalcone on NF-κB and the inflammatory response during myocardial ischemia reperfusion injury in rats.

The aim of this study was to investigate the effect of 17-methoxyl-7-hydroxy-benzene-furanchalcone (MHBFC) on nuclear factor-kappa-binding (NF-κB) and the inflammatory response in rats with myocardial ischemia reperfusion injury (MI/RI). Sprague-Dawley rats were randomly divided into 7 groups, and the rat MI/RI model was established by the ligation of the left anterior descending for 30 minutes followed by ligation release for 1 hour. Areas of myocardial infarction were measured using Evans blue-2,3,5-Triphenyltetrazolium chloride (TTC) staining. Levels of malondialdehyde, glutathione peroxidase, and total superoxide dismutase were assessed. Release of interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and interleukin-10 (IL-10) was measured by means of an enzyme-linked immunosorbent assay. NF-κBp65 and intercellular adhesion molecule-1 protein expression and caspase-3 and adenine nucleotide translocator-1 messenger RNA expression were evaluated by immunohistochemistry and reverse transcription polymerase chain reaction, respectively. Pretreatment with MHBFC decreased the infarction areas, the malondialdehyde, IL-1ß and IL-6 levels, the expression of caspase-3, NF-κBp65, and intercellular adhesion molecule-1. Further, MHBFC increased total superoxide dismutase and glutathione peroxidase activities, the release of IL-10, and the expression of adenine nucleotide translocator-1 messenger RNA compared with the results of the model group. The experiment showed that MHBFC protected the heart against MI/RI possibly by reducing lipid peroxidation damage while inhibiting the activity of NF-κBp65 and the inflammatory response.

Protective effect of genistein on lipopolysaccharide/D-galactosamine- induced hepatic failure in mice.

This study examined the effect of genistein from Hydrocotyle sibthorpioides on lipopolysaccharide (LPS)/D-galactosamine (D-GalN)-induced acute hepatic failure. Compared to the model control, genistein treatment significantly protected against LPS/D-GalN-induced liver injury, as evidenced by the decrease in serum alanine and aspartate aminotransferases activities and the attenuation of histopathological changes. Furthermore, genistein alleviated the pro-inflammatory cytokines including tumor necrosis factor-alpha (TNF-α) and nitric oxide (NO)/inducible nitric oxide synthase (iNOS) by inhibiting nuclear factor-κB (NF- κB) activity. Genistein attenuated the elevated level of caspases-3, while augmented the expression of Bcl-2. In addition, LPS/D-GalN induced significant increase of heme oxygenase (HO), carbon monoxide and bilirubin levels and these alterations were augmented by genistein treatment. In conclusion, the protective effect of genistein on LPS/D-GalN-induced liver damage was mainly due to its ability to block NF-κB signaling pathway for anti-inflammation response, attenuate hepatocellular apoptosis and increase HO level. These findings suggest that genistein can be considered as a potential agent for preventing acute hepatic failure.

Puerarin alleviates diabetic nephropathy by inhibiting Caspase-1-mediated pyroptosis.

BACKGROUND AND PURPOSE: Diabetic nephropathy (DN) is an important cause of end-stage renal disease, with podocyte injury as the main feature. Pyroptosis plays a non-negligible role in the process of diabetic nephropathy. Puerarin (PR) treatment of diabetic nephropathy has great potential, but the mechanism is not very clear. This article aims to study the protective effect and mechanism of puerarin on DN. METHODS: Streptozotocin (STZ)-induced C57 BL/6J mouse model of DN was given PR, Necrosulfomide (NSA), Nigericin for 12 weeks; A 60 mM high glucose(HG) induced MPC5 cell injury model was administered to PR, NSA, and Nigericin interventions for 24 h. RESULTS: After 12 weeks of administration, PR reduced fasting blood glucose levels in DN mice, alleviated glomerular lesions, reduced podocyte damage, and protected renal function. Meanwhile, PR also inhibits the expression of pyroptosis-related proteins. In addition, PR alleviated the release of Interleukin 18 (IL-18), Interleukin 1beta (IL-1ß), and lactate dehydrogenase (LDH) in MPC5 cells under HG conditions, downregulated the expression of pyrozozois-related proteins, and improved Caspase-1-mediated pyroptosis in MPC5 cells. CONCLUSION: Our study suggests that the beneficial effects of PR in diabetic nephropathy may be associated with inhibition of Caspase-1-mediated pyroptosis.

Asiatic acid from Potentilla chinensis attenuate ethanol-induced hepatic injury via suppression of oxidative stress and Kupffer cell activation.

This study examined the effect of Asiatic acid from Potentilla chinensis (AAPC) on chronic ethanol-induced hepatic injury. Rats underwent intragastric administration of ethanol (5.0­9.0 g/kg) once a day for 12 weeks. A subset of rats were also intragastrically treated with AAPC (2, 4 or 8 mg/kg) once a day. In the end, AAPC treatment significantly protected against ethanol-induced liver injury, as evidenced by the decrease in serum alanine and aspartate aminotransferases levels and the attenuation of histopathological changes in rats. Additionally, AAPC significantly decreased blood alcohol and acetaldehyde concentrations by enhancing alcohol dehydrogenase and aldehyde dehydrogenase activities. Mechanistically, studies showed that AAPC remarkably alleviated the formations of malondialdehyde and myeloperoxidase, restored impaired antioxidants, including superoxide dismutase, glutathione peroxidase, glutathione reductase and catalase, and inhibited cytochrome P450 (CYP)2E1 activity. Moreover, the over-expression of cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), the elevated plasma endotoxin level and the up-regulated Toll-like receptor 4 (TLR4), CD14 and myeloid differentiation factor 88 (MyD88) as well as nuclear factor-κB were also suppressed by AAPC in ethanol-intoxicated rats. In conclusion, the protective effect of AAPC on ethanol-induced hepatotoxicity was mainly due to its ability to attenuate oxidative stress and inhibit Kupffer cell activation by decreasing the level of plasma endotoxin and the expression of TLR4, CD14 and MyD88.

Pressor mechanism evaluation for phytochemical compounds using in silico compound-protein interaction prediction.

In this study, a method was applied to evaluate pressor mechanisms through compound-protein interactions. Our method assumed that the compounds with different pressor mechanisms should bind to different target proteins, and thereby these mechanisms could be differentiated using compound-protein interactions. Twenty-six phytochemical components and 46 tested target proteins related to blood pressure (BP) elevation were collected. Then, in silico compound-protein interactions prediction probabilities were calculated using a random forest model, which have been implemented in a web server, and the credibility was judged using related literature and other methods. Further, a heat map was constructed, it clearly showed different prediction probabilities accompanied with hierarchical clustering analysis results. Followed by a compound-protein interaction network was depicted according to the results, we can see the connectivity layout of phytochemical components with different target proteins within the BP elevation network, which guided the hypothesis generation of poly-pharmacology. Lastly, principal components analysis (PCA) was carried out upon the prediction probabilities, and pressor targets could be divided into three large classes: neurotransmitter receptors, hormones receptors and monoamine oxidases. In addition, steroid glycosides seem to be close to the region of hormone receptors, and a weak difference existed between them. This work explored the possibility for pharmacological or toxicological mechanism classification using compound-protein interactions. Such approaches could also be used to deduce pharmacological or toxicological mechanisms for uncharacterized compounds.

ATNet: A Defect Detection Framework for X-ray Images of DIP Chip Lead Bonding.

In order to improve the production quality and qualification rate of chips, X-ray nondestructive imaging technology has been widely used in the detection of chip defects, which represents an important part of the quality inspection of products after packaging. However, the current traditional defect detection algorithm cannot meet the demands of high accuracy, fast speed, and real-time chip defect detection in industrial production. Therefore, this paper proposes a new multi-scale feature fusion module (ATSPPF) based on convolutional neural networks, which can more fully extract semantic information at different scales. In addition, based on this module, we design a deep learning model (ATNet) for detecting lead defects in chips. The experimental results show that at 8.2 giga floating point operations (GFLOPs) and 146 frames per second (FPS), mAP0.5 and mAP0.5-0.95 can achieve an average accuracy of 99.4% and 69.3%, respectively, while the detection speed is faster than the baseline yolov5s by nearly 50%.