The Ethanolic Extract of Lindera aggregata Modulates Gut Microbiota Dysbiosis and Alleviates Ethanol-Induced Acute Liver Inflammation and Oxidative Stress SIRT1/Nrf2/NF-κB Pathway.

This study is an attempt to evaluate the therapeutic effect of the ethanolic extract of Lindera aggregata on the liver and intestinal microbiota in rats with alcohol-induced liver injury (ALI). Rats were treated with 70 mg probiotics, 1 g/kg, 2 g/kg, and 3 g/kg ethanolic extract of Lindera aggregata, respectively, for 10 days. We found that Lindera aggregata could significantly reduce the biochemical parameters in the serum of ALD rats. Lindera aggregata alleviates oxidative stress and inflammation by upregulating SIRT1 and Nrf2 and downregulating COX2 and NF-κB. The results of 16S rRNA gene sequencing showed that the medium dose of Lindera aggregata had the best effect on the growth of beneficial bacteria. Diversity analysis and LEfSe analysis showed that beneficial bacteria gradually occupied the dominant niche. The relative abundance of potential pathogens in the gut decreased significantly. We demonstrated that the ethanolic extract of Lindera aggregata can alleviate the oxidative stress and inflammation induced by alcohol through the SIRT1/Nrf2/NF-κB pathway and can modulate the disturbance of gut microbiota induced by alcohol intake.

Quamoclit angulata extract supplementation attenuates hepatic damage via regulation of AMPK/SIRT associated hepatic lipid metabolism in streptozotocin and high fat diet-induced T2DM mice.

Quamoclit angulata (QA) is a species of the Convolvulaceae family and has a regulatory effect on glucose homeostasis. However, the effects of QA on hyperglycemia-induced hepatic damage has not been elucidated. We hypothesized that QA extract (QAE) would alleviate hepatic damage through regulation of hepatic lipid accumulation in type 2 diabetes mellitus (T2DM). T2DM was induced by streptozotocin-high-fat diet in C57BL6 male mice for 8 weeks. The diabetic mice were supplemented with QAE at low dose (5 mg/kg) or high dose (HQ, 10 mg/kg) by oral gavage every day for 12 weeks. Histopathological changes in hepatic tissue were examined using hematoxylin and eosin staining, and the protein levels of biomarkers related to AMP-activation kinase (AMPK)/sirtuin-1 (SIRT1)-associated lipid metabolism were measured using Western blotting. QAE supplementation ameliorated plasma insulin and glycated hemoglobin in diabetic mice. Furthermore, QAE decreased hepatic lipid accumulation demonstrated by hepatic triglyceride and cholesterol levels. QAE supplementation induced hepatic AMPK, which activates SIRT1 accompanied by reduced lipogenesis in the HQ group. These changes were partially explained by the amelioration of advanced glycation end product, hepatic oxidative stress, inflammation, and fibrosis in diabetic mice. Altogether, QAE would be a potential nutraceutical to prevent hepatic damage by regulation of AMPK/SIRT1-associated lipid metabolism through oxidative stress, inflammation, and fibrosis in T2DM.

Prognostic value of baseline imaging and clinical features in patients with advanced hepatocellular carcinoma.

AIMS: To investigate the prognostic value of baseline imaging features for overall survival (OS) and liver decompensation (LD) in patients with hepatocellular carcinoma (HCC). DESIGN: Patients with advanced HCC from the SORAMIC trial were evaluated in this post hoc analysis. Several radiological imaging features were collected from baseline computed tomography (CT) and magnetic resonance imaging (MRI) imaging, besides clinical values. The prognostic value of these features for OS and LD (grade 2 bilirubin increase) was quantified with univariate Cox proportional hazard models and multivariate Least Absolute Shrinkage and Selection Operator (LASSO) regression. RESULTS: Three hundred and seventy-six patients were included in this study. The treatment arm was not correlated with OS. LASSO showed satellite lesions, atypical HCC, peritumoral arterial enhancement, larger tumour size, higher albumin-bilirubin (ALBI) score, liver-spleen ratio <1.5, ascites, pleural effusion and higher bilirubin values were predictors of worse OS, and higher relative liver enhancement, smooth margin and capsule were associated with better OS. LASSO analysis for LD showed satellite lesions, peritumoral hypointensity in hepatobiliary phase, high ALBI score, higher bilirubin values and ascites were predictors of LD, while randomisation to sorafenib arm was associated with lower LD. CONCLUSIONS: Imaging features showing aggressive tumour biology and poor liver function, in addition to clinical parameters, can serve as imaging biomarkers for OS and LD in patients receiving sorafenib and selective internal radiation therapy for HCC.

The transcatheter arterial chemoembolization combined with targeted nanoparticle delivering sorafenib system for the treatment of microvascular invasion of hepatocellular carcinoma.

to explore the value of transcatheter arterial chemoembolization (TACE) combined with targeted nanoparticle delivery system for sorafenib (SFB) to treat hepatocellular carcinoma (HCC) with microvascular invasion. 42 HCC patients with microvascular invasion after liver cancer surgery were selected from our hospital from December 2020 and February 2021. Patients were divided into experimental group and control group based on their willingness. Patients in experimental group (18 cases) were treated with combination therapy of TACE and Ab-SFB-NP system; while patients in control group (24 cases) took TACE and non-nano drug delivery system. There was no obvious difference in liver function and blood test results between two groups of patients before treatment and one month after treatment (P > 0.05). Three months after treatment, differences of alanine aminotransferase (ALT) were statistically significant (P < 0.05); while differences of other test results were not (P > 0.05). The disease control rate (DCR) of patients in experimental group was higher slightly (P > 0.05). The incidence of adverse reactions of patients in experimental group was lower than the control group and the differences were statistically significant (P < 0.05). After three months of TACE, the DCR in the experimental group was significantly higher compared to control group. The toxic reactions of taking SFB with Ab-SFB-NP nano-drug delivery system mainly included hand-foot syndrome, diarrhea, and bleeding, the toxic reactions were mainly at level 1 ~ 2. After symptomatic treatment, the toxicity was effectively controlled, so the security was high.

Reenvisioning Traditional to Regenerative Therapeutic Advances in Managing Nonalcoholic Fatty Liver Disease in Diabetes Mellitus.

Reports indicate the increasing prevalence of liver disorders in diabetes mellitus (DM) patients. Clinically, it has also been revealed that the existence of nonalcoholic fatty liver disease (NAFLD) enhances the incidence of type 2 diabetes mellitus (T2DM), while T2DM exacerbates NAFLD to extremely severe forms of steatohepatitis, cirrhosis, and hepatocellular carcinoma. This implies the coexistence and bidirectional nature of NAFLD and T2DM, which function synergistically to drive adverse consequences in clinical practice. For treatment of such comorbid state, though the existing practices such as lifestyle management, traditional Chinese medicines (TCM), and pharmaceuticals have offered somewhat relief, the debate continues about the optimal therapeutic impacts. Recent developments in the field of tissue engineering have led to a renewed interest in novel biomaterial alternatives such as stem cells. This might be attributable to their differentiation potential towards hepatic and pancreatic lineage. These cellular therapies could be further complemented by platelet-derived biomaterials, TCM formulations, or any specific drug. Based on these abovementioned approaches, we aimed to comprehensively analyze various preclinical and clinical studies from traditional to regenerative therapeutic approaches in managing concomitant NAFLD and T2DM.

Target identification of hepatic fibrosis using Pien Tze Huang based on mRNA and lncRNA.

Hepatic fibrosis is a spontaneous wound-healing response triggered by chronic liver injury. Pien Tze Huang (PZH), a traditional Chinese herbal medicine, has been widely used to treat various hepatic diseases in Asia. We used a CCl4-induced mouse model to establish a PZH group of hepatic fibrosis mice treated with PZH and a control group of hepatic fibrosis mice without any treatment. We performed RNA-seq and mass spectrometry sequencing to investigate the mechanism of the PZH response in hepatic fibrosis and identified multiple differentially expressed transcripts (DETs) and proteins (DEPs) that may be drug targets of PZH. Liver functional indices, including serum albumin (ALB), alanine aminotransferase (ALT) and aspartate aminotransferase (AST), were significantly decreased in the PZH treatment group (P < 0.05) in the eighth week. Hematoxylin-eosin (HE), Masson and Sirius red staining demonstrated that PZH significantly inhibited infiltration of inflammatory cells and collagen deposition. A total of 928 transcripts and 138 proteins were differentially expressed in PZH-treated mice compared to the control group. Gene Ontology (GO) enrichment analysis suggested that PZH may alleviate liver injury and fibrosis by enhancing the immune process. Taken together, our results revealed that multiple DETs and DEPs may serve as drug targets of PZH in hepatic fibrosis patient in future clinical practice.

Role of circadian rhythm and autonomic nervous system in liver function: a hypothetical basis for improving the management of hepatic encephalopathy.

Hepatic encephalopathy (HE) is a common, incapacitating complication of cirrhosis that affects many patients with cirrhosis. Although several therapies have proven effective in the treatment and prevention of this condition, several patients continue to suffer from covert disease or episodes of relapse. The circadian rhythm has been demonstrated to be pivotal for many body functions, including those of the liver. Here, we explore the impact of circadian rhythm-dependent signaling on the liver and discuss the evidence of its impact on liver pathology and metabolism. We describe the various pathways through which circadian influences are mediated. Finally, we introduce a novel method for improving patient response to drugs aimed at treating HE by utilizing the circadian rhythm. A digital system that introduces a customization-based technique for improving the response to therapies is presented as a hypothetical approach for improving the effectiveness of current medications used for the treatment of recurrent and persistent hepatic encephalopathy.

Reaching Deeper: Absolute In Vivo Thermal Reading of Liver by Combining Superbright Ag2S Nanothermometers and In Silico Simulations.

Luminescent nano-thermometry is a fast-developing technique with great potential for in vivo sensing, diagnosis, and therapy. Unfortunately, it presents serious limitations. The luminescence generated by nanothermometers, from which thermal readout is obtained, is strongly distorted by the attenuation induced by tissues. Such distortions lead to low signal levels and entangle absolute and reliable thermal monitoring of internal organs. Overcoming both limitations requires the use of high-brightness luminescent nanothermometers and adopting more complex approaches for temperature estimation. In this work, it is demonstrated how superbright Ag2S nanothermometers can provide in vivo, reliable, and absolute thermal reading of the liver during laser-induced hyperthermia. For that, a new procedure is designed in which thermal readout is obtained from the combination of in vivo transient thermometry measurements and in silico simulations. The synergy between in vivo and in silico measurements has made it possible to assess relevant numbers such as the efficiency of hyperthermia processes, the total heat energy deposited in the liver, and the relative contribution of Ag2S nanoparticles to liver heating. This work provides a new way for absolute thermal sensing of internal organs with potential application not only to hyperthermia processes but also to advanced diagnosis and therapy.

Beneficial effects of natural compounds on experimental liver ischemia-reperfusion injury.

Liver ischemia-reperfusion injury (IRI) is a phenomenon inherent to hepatic surgery that severely compromises the organ functionality, whose underlying mechanisms involve cellular and molecular interrelated processes leading to the development of an excessive inflammatory response. Liver resident cells and those recruited in response to injury generate pro-inflammatory signals such as reactive oxygen species, cytokines, chemokines, proteases and lipid mediators that contribute to hepatocellular necrosis and apoptosis. Besides, dying hepatocytes release damage-associated molecular patterns that actívate inflammasomes to further stimulate inflammatory responses leading to massive cell death. Since liver IRI is a complication of hepatic surgery in man, extensive preclinical studies have assessed potential protective strategies, including the supplementation with natural compounds, with the objective to downregulate nuclear factor-κB functioning, the main effector of inflammatory responses. This can be accomplished by either the activation of peroxisome proliferator-activated receptor-α, G protein-coupled receptor 120 or antioxidant signaling pathways, the synthesis of specific pro-resolving mediators, downregulation of Toll-like receptor 4 activity or additional contributory mechanisms that are beginning to be understood. The latter aspect is a crucial issue to be accomplished in preclinical studies, in order to establish adequate conditions for the supplementation with natural products before major liver surgeries in man involving warm IR, such as hepatic trauma or resection of large intrahepatic tumors.

Clinical study on acupuncture treatment of hypertension with hyperactivity of liver yang.

INTRODUCTION: Hypertension can lead to different degrees complications of cardiovascular and cerebrovascular, and increase the risk of sudden death. Acupuncture has become a complementary alternative therapy for hypertension because of its antihypertensive and nontoxic side effects. However, there is still lack of evidence-based medicine evidence for an effective acupuncture antihypertensive prescription. The purpose of this study is to evaluate the effect of a special acupuncture prescription on hypertension with hyperactivity of liver yang. METHODS: In this randomized controlled trial, we will recruit 56 hypertensive patients with hyperactivity of liver yang. Then the patients will be randomly divided into control group and experimental group. The control group will be treated with western medicine, and the experimental group will be treated with medicine combined with acupuncture. The intervention will last 4 weeks. The indices will be collected before acupuncture, after acupuncture, and 2 weeks after acupuncture. The primary outcome will be 24-hour ambulatory blood pressure. The secondary outcomes will be clinic blood pressure, anxiety and depression score, and the syndrome score of hyperactivity of liver yang. The auxiliary indicators will be blood pressure load values and salt sensitivity risk rate. The exploratory indicator will be acupoint diagnosis. The safety evaluation indicator will be incidence of adverse events. DISCUSSION: The results of this study will provide favorable evidence for the efficacy and safety of acupuncture in reducing blood pressure, and explore the positive reaction acupoints which related to hypertension.

Chemical Profile of Launaea nudicaulis Ethanolic Extract and Its Antidiabetic Effect in Streptozotocin-Induced Rats.

Launaea nudicaulis is used in folk medicine worldwide to treat several diseases. The present study aimed to assess the antidiabetic activity of L. nudicaulis ethanolic extract and its effect on diabetic complications in streptozotocin-induced hyperglycemic rats. The extract was orally administrated at 250 and 500 mg/kg/day for 5-weeks and compared to glibenclamide as a reference drug at a dose of 5 mg/kg/day. Administration of the extract exhibited a potential hypoglycemic effect manifested by a significant depletion of serum blood glucose concurrent with a significant elevation in serum insulin secretion. After 5-weeks, extract at 250 and 500 mg/kg/day decreased blood glucose levels by about 53.8 and 68.1%, respectively, compared to the initial values (p ≤ 0.05). The extract at the two dosages prevented weight loss of rats from the 2nd week till the end of the experiment, compared to diabetic control rats. The extract further exhibited marked improvement in diabetic complications including liver, kidney and testis performance, oxidative stress, and relative weight of vital organs, with respect to diabetic control. Histopathological examinations confirmed the previous biochemical analysis, where the extract showed a protective effect on the pancreas, liver, kidney, and testis that degenerated in diabetic control rats. To characterize extract composition, UPLC-ESI-qTOF-MS identified 85 chromatographic peaks belonging to flavonoids, phenolics, acyl glycerols, nitrogenous compounds, and fatty acids, with four novel phenolics reported. The potential anti-diabetic effect warrants its inclusion in further studies and or isolation of the main bioactive agent(s).

Epigallocatechin-3-Gallate Dampens Non-Alcoholic Fatty Liver by Modulating Liver Function, Lipid Profile and Macrophage Polarization.

Epigallocatechin-3-gallate (EGCG) has been shown to attenuate obesity, fatty liver disease, hepatic inflammation and lipid profiles. Here, we validate the efficacy of EGCG in a murine model of non-alcoholic fatty liver disease (NAFLD) and extend the mechanistic insights. NAFLD was induced in mice by a high-fat diet (HFD) with 30% fructose. EGCG was administered at a low dose (25 mg/kg/day, EGCG-25) or high dose (50 mg/kg/day, EGCG-50) for 8 weeks. In HFD-fed mice, EGCG attenuated body and liver weight by ~22% and 47%, respectively, accompanied by ~47% reduction in hepatic triglyceride (TG) accumulation and ~38% reduction in serum cholesterol, resonating well with previous reports in the literature. In EGCG-treated mice, the hepatic steatosis score and the non-alcoholic steatohepatitis activity score were both reduced by ~50% and ~57%, respectively, accompanied by improvements in hepatic inflammation grade. Liver enzymes were improved ~2-3-fold following EGCG treatment, recapitulating previous reports. Hepatic flow cytometry demonstrated that EGCG-fed mice had lower Ly6C+, MHCII+ and higher CD206+, CD23+ hepatic macrophage infiltration, indicating that EGCG impactedM1/M2 macrophage polarization. Our study further validates the salubrious effects of EGCG on NAFLD and sheds light on a novel mechanistic contribution of EGCG, namely hepatic M1-to-M2 macrophage polarization. These findings offer further support for the use of EGCG in human NAFLD.

Non-alcoholic fatty liver disease: An overview of risk factors, pathophysiological mechanisms, diagnostic procedures, and therapeutic interventions.

Non-alcoholic fatty liver disease (NAFLD) is a disorder of excessive fat accumulation in the liver, known as steatosis, without alcohol overconsumption. NAFLD can either manifest as simple steatosis or steatohepatitis, known as non-alcoholic steatohepatitis (NASH), which is accompanied by inflammation and possibly fibrosis. Furthermore, NASH might progress to hepatocellular carcinoma. NAFLD and NASH prevalence is in a continuous state of growth, and by 2018, NAFLD became a devastating metabolic disease with a global pandemic prevalence. The pathophysiology of NAFLD and NASH is not fully elucidated, but is known to involve the complex interplay between different metabolic, environmental, and genetic factors. In addition, unhealthy dietary habits and pre-existing metabolic disturbances together with other risk factors predispose NAFLD development and progression from simple steatosis to steatohepatitis, and eventually to fibrosis. Despite their growing worldwide prevalence, to date, there is no FDA-approved treatment for NAFLD and NASH. Several off-label medications are used to target disease risk factors such as obesity and insulin resistance, and some medications are used for their hepatoprotective effects. Unfortunately, currently used medications are not sufficiently effective, and research is ongoing to investigate the beneficial effects of different drugs and phytochemicals in NASH. In this review article, we outline the different risk factors and pathophysiological mechanisms involved in NAFLD, diagnostic procedures, and currently used management techniques.

Effect of vitamin D3 supplementation on hepatic lipid dysregulation associated with autophagy regulatory AMPK/Akt-mTOR signaling in type 2 diabetic mice.

Vitamin D3 has been reported to protect liver against non-alcoholic fatty liver disease (NAFLD) by attenuating hepatic lipid dysregulation in type 2 diabetes mellitus (T2DM). However, the mechanism of vitamin D3 on hepatic lipid metabolism-associated autophagy in hyperglycemia-induced NAFLD remains yet to be exactly elucidated. C57BL/6J mice were intraperitoneally injected with 30 mg/kg of streptozotocin and fed a high-fat diet for induction of diabetes. All mice were administered with vehicle or vitamin D3 (300 ng/kg or 600 ng/kg) by oral gavage for 12 weeks. Histological demonstrations of the hepatic tissues were obtained by H&E staining and the protein levels related to lipid metabolism and autophagy signaling were analyzed by Western blot. Treatment with vitamin D3 improved insulin resistance, liver damage, and plasma lipid profiles, and decreased hepatic lipid content in the diabetic mice. Moreover, vitamin D3 administration ameliorated hepatic lipid dysregulation by downregulating lipogenesis and upregulating lipid oxidation under diabetic condition. Importantly, vitamin D3 treatment induced autophagy by activating AMP-activated protein kinase (AMPK), inactivating Akt and ultimately blocking mammalian target of rapamycin (mTOR) activation in the T2DM mice. Additionally, vitamin D3 was found to be effective in anti-apoptosis and anti-fibrosis in the liver of diabetic mice. The results suggested that vitamin D3 may ameliorate hepatic lipid dysregulation by activating autophagy regulatory AMPK/Akt-mTOR signaling in T2DM, providing insights into its beneficial effects on NAFLD in type 2 diabetic patients.

Assessment of hepatic functions, hematopoietic cytokines and haematological parameters in people occupationally exposed to volatile petroleum hydrocarbons.

Humans are occupationally exposed to volatile petroleum hydrocarbons through inhalation and ingestion. To access the effect of exposure to volatile hydrocarbons, hematopoietic cytokines, haematological parameters and hepatic functions were assayed for in 100 subjects. Male participants showed significant increase (p < 0.05) in erythropoietin, interleukin-3, alanine transaminase (ALT), alkaline phosphatase (ALP), mean cell hemoglobin concentration (MCHC), mean cell volume (MCV) and significant decrease (p < 0.05) in mean cell hemoglobin (MCH). Female participants showed significant increase (p < 0.05) in interleukin-3, ALT, AST, ALP, MCHC, MCV and significant decrease (p < 0.05) in MCH, platelets, hemoglobin and hematocrit compared to their controls. Exposure to volatile petroleum hydrocarbons raised the absolute red blood cell indices and liver enzymes and could stimulate combined increase in the release of erythropoietin and interleukin-3 leading to ineffective hematopoiesis.

Role of anthraquinones in Cassia occidentalis induced hepato-myo-encephalopathy.

ETHNOPHARMACOLOGICAL RELEVANCE: The different plant parts of Cassia occidentalis Linn, (CO) such as root, leaves, seeds and pods have traditionally been used in multifarious medicines for the treatment of dysentery, diarrhea, constipation, fever, eczema, cancer and venereal diseases. MATERIALS AND METHODS: A systematic search of literature has been done in books and scientific databases like Science Direct, Pubmed, Google Scholar and Scopus etc. These sources were used to compile, analyze and review the information regarding the phytochemistry, toxicology and mechanism of toxicity of CO. The various references on this subject are cited in our review ranging from 1956 to 2019. RESULTS: Unintentional exposure of CO causes serious pathological condition in children, known as hepato-myo-encephalopathy (HME). The toxicity after CO consumption is associated with the presence of anthraquinones (AQs), a class of secondary plant metabolites. These AQs at high concentrations are known to cause detrimental effects on essential vital organs such as liver, kidney, spleen, brain, muscle and reproductive organs. The animal studies in rodent models as well as clinical investigations have clearly revealed that CO toxicity is associated with enhanced hepatotoxicity serum markers (ALT, AST, and LDH) and presence of necrotic lesions in liver. Furthermore, CO also causes vacuolization in muscle tissue and increases the level of CPK which is a prominent muscle damage marker. Apart from these target organs, CO consumption also causes neuronal damage via disturbing the levels of different proteins such as (GFAP and b-tubulin III). The mechanistic studies show that AQs present in CO have the potential to disturb the cellular homeostasis via binding to DNA, increasing the production ROS and showing inhibitory effects on essential enzymes etc. Therefore, AQs have been observed to be the primary culprit agents contributing to the toxicity of CO in children and animals. CONCLUSION: Despite its therapeutic potential, CO consumption can be detrimental if consumed in high amounts. A thorough analysis of literature reveals that AQs are the primary factors contributing to toxicity of CO seeds. Exposure to CO seeds causes HME, which is a serious life threatening condition for the malnourished children from lower strata. Multiple mechanisms are involved in the CO induced HME in patients. Lack of appropriate diagnostic measures and a poor understanding of the CO toxicity mechanism in humans and animals complicate the clinical management of CO poisoning subjects. Therefore, development of point of care diagnostic kits shall help in early diagnosis & suitable management of CO poisoning.

Epigallocatechin gallate decreases plasma triglyceride, blood pressure, and serum kisspeptin in obese human subjects.

Obesity is one of major risk factors increasing chronic diseases including type II diabetes, cardiovascular diseases, and hypertension. The effects of epigallocatechin gallate (EGCG), the major active compound in green tea, on reduced obesity and improved metabolic profiles are still controversial. Furthermore, the effects of EGCG on human adipocyte lipolysis and browning of white adipocytes have not been elucidated. This study aimed to investigate the effects of EGCG on obesity, lipolysis, and browning of human white adipocytes. The results showed that, when compared to the baseline values, EGCG significantly decreased fasting plasma triglyceride levels (P < 0.05), systolic blood pressure (P < 0.05), diastolic blood pressure (P < 0.05), and serum kisspeptin levels (P < 0.05) after 8 weeks of supplement. On the other hand, supplement of EGCG in obese human subjects for 4 or 8 weeks did not decrease body weight, body mass index, waist and hip circumferences, nor total body fat mass or percentage when compared to their baseline values. The study in human adipocytes showed that EGCG did not increase the glycerol release when compared to vehicle, suggesting that it had no lipolytic effect. Furthermore, treatment of EGCG did not enhance uncoupling protein 1 (UCP1) mRNA expression in human white adipocytes when compared with treatment of pioglitazone, the peroxisome proliferator-activated receptor γ (PPAR-γ) agonist, suggesting that EGCG did not augment the browning effect of PPAR-γ on white adipocytes. This study revealed that EGCG reduced 2 metabolic risk factors which are triglyceride and blood pressure in the human experiment. We also showed a novel evidence that EGCG decreased kisspeptin levels. However, EGCG had no effects on obesity reduction in humans, lipolysis, nor browning of human white adipocytes.

[Xiongcan Yishen Prescription upregulates the expressions of eNOS and cGMP in the penile tissue of ED rats with liver depression and kidney deficiency].

OBJECTIVE: To investigate the effect of Xiongcan Yishen Prescription (XYP) on the expressions of eNOS and cGMP in the penile tissue of ED rats with liver depression and kidney deficiency (LDKD). METHODS: The model of ED-LDKD was established in 30 eight-week-old SPF-class male SD rats by injecting hydrocortisone intramuscularly and binding the limbs for 14 days, and another 10 rats were taken as blank controls. Then, the model rats were randomized into six groups of equal number and treated intragastrically with distilled water (model control), tadalafil tablets at 0.52 mg/kg/d (tadalafil control), Shugan Yiyang Capsules 0.3125 g/kg/d (SYC control), and XYP at 10.4 g/kg/d (low-dose XYP), 20.8 g/kg/d (medium-dose XYP) and 41.6 g/kg/d (high-dose XYP), bid, for 28 successive days, respectively. Before and after modeling and after 28-day treatment, the animals were subjected to tail suspension and mating tests. The next day after medication, the penile tissues of the rats were harvested for determining the expression levels of eNOS and cGMP proteins by immunohistochemical analysis of the mean optical density. RESULTS: Compared with the model controls, the rats of the high-, medium- and low-dose XYP and SYC control groups all showed significant decreases in the tail suspension time (ï¼»3.17 ± 0.11ï¼½ vs ï¼»2.58 ± 0.25ï¼½, ï¼»2.52 ± 0.31ï¼½, ï¼»2.51 ± 0.3ï¼½ and ï¼»2.57 ± 0.29ï¼½ min, P < 0.05) and mount latency (ML) (ï¼»9.23 ± 0.11ï¼½ vs ï¼»1.21 ± 0.12ï¼½, ï¼»2.17 ± 0.16ï¼½, ï¼»2.26 ± 0.13ï¼½, ï¼»1.23 ± 0.15ï¼½ and ï¼»2.48 ± 0.18ï¼½ min, P < 0.05) but increases in mount frequency (MF) (ï¼»0.48 ± 0.18ï¼½ vs ï¼»3.29 ± 0.11ï¼½, ï¼»3.18 ± 0.11ï¼½, ï¼»3.05 ± 0.05ï¼½, ï¼»3.23 ± 0.12ï¼½ and ï¼»3.2 ± 0.28ï¼½ times, P < 0.05) and intromission frequency (IF) (ï¼»0.8 ± 0.84ï¼½ vs ï¼»11.8 ± 0.84ï¼½, ï¼»11.2 ± 1.48ï¼½, ï¼»9.4 ± 1.14ï¼½, ï¼»11.4 ± 1.14ï¼½ and ï¼»10 ± 1.22ï¼½ times, P < 0.05). The eNOS and cGMP proteins were mainly expressed in the nucleus and cytoplasm of the arterial and venous endothelial cells and sinusoidal endothelial cells of the cavernous, as brownish yellow particles in a scattered and focal pattern. Both the expressions of eNOS and cGMP in the penile tissue were remarkably upregulated in the high-, medium- and low-dose XYP and SYC control groups as compared with those in the model control (P < 0.05) but exhibited no statistically significant difference between the tadalafil and model control groups (P > 0.05). CONCLUSIONS: Xiongcan Yishen Prescription can relieve the depression symptoms, increase the mount frequency, activate the NO/cGMP pathway, and upregulate the expressions of eNOS and cGMP in the penile tissue of ED rats with liver depression and kidney deficiency.

Muscle-Liver Trafficking of BCAA-Derived Nitrogen Underlies Obesity-Related Glycine Depletion.

Glycine levels are inversely associated with branched-chain amino acids (BCAAs) and cardiometabolic disease phenotypes, but biochemical mechanisms that explain these relationships remain uncharted. Metabolites and genes related to BCAA metabolism and nitrogen handling were strongly associated with glycine in correlation analyses. Stable isotope labeling in Zucker fatty rats (ZFRs) shows that glycine acts as a carbon donor for the pyruvate-alanine cycle in a BCAA-regulated manner. Inhibition of the BCAA transaminase (BCAT) enzymes depletes plasma pools of alanine and raises glycine levels. In high-fat-fed ZFRs, dietary glycine supplementation raises urinary acyl-glycine content and lowers circulating triglycerides but also results in accumulation of long-chain acyl-coenzyme As (acyl-CoAs), lower 5' adenosine monophosphate-activated protein kinase (AMPK) phosphorylation in muscle, and no improvement in glucose tolerance. Collectively, these studies frame a mechanism for explaining obesity-related glycine depletion and also provide insight into the impact of glycine supplementation on systemic glucose, lipid, and amino acid metabolism.

Hepatotoxic Effect of Oral Zinc Oxide Nanoparticles and the Ameliorating Role of Selenium in Rats: A histological, immunohistochemical and molecular study.

Despite the emerging concerns about the hepatotoxic risks associated with Zinc oxide nanoparticles (ZnO NPs), yet, the morphological and molecular alterations associated with these extensively-used nanoparticles remain to be elucidated. Thus, the current study has been designed to analyze the effect of ZnO NPs on the hepatic histopathological and immunohistochemical changes, along with the modulation of the oxidative-stress induced JNK/p38MAPK and the STAT-3 signalling. The study also explored the potential protective role of selenium against those alterations. ZnO NPs disrupted the hepatic architecture, elevated the serum liver enzyme alanine transaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase (ALP) levels and caused dose-dependent decrease in the activity of the antioxidant enzymes glutathione-peroxidase, superoxide dismutase and catalase along with an increase in the lipid peroxidation product malondialdehyde. ZnO NPs also increased the area of immune-reactivity of the apoptotic protein bax and decreased the area of immune-reactivity of the anti-apoptotic protein bcl2 together with augmentation of the hepatic caspase 3 gene expression. The role of selenium in ameliorating the hepatotoxicity, oxidative stress injury, and apoptosis induced by ZnO-NPs, along with its role in modulating the JNK/p38MAPK and the STAT-3 signalling and improving the histopathological hepatic changes, offers selenium as a promising adjunctive therapy in individuals subjected to high concentrations of ZnO NPs especially in cases of extensive occupational, medicinal and industrial exposure.