[Research progress in epigenetic pharmacological effects of rhein].

Rhein, which is one of the main active components of Rheum palmatum, has a range of pharmacological activities such as the regulation of the metabolism of glucose and lipids, anti-inflammatory, anti-tumor, anti-fibrosis, etc. Epigenetics refers to the heritable variation of gene expression without altering the DNA sequence. It is involved in the emergence and development of inflammation, renal fibrosis, diabetes, cancer, atherosclerosis, and other diseases, thus becoming a new strategy for the treatment of many di-seases. A series of studies have shown that epigenetic modification may be a common molecular mechanism of various pharmacological effects of rhein. This paper summarized the effects of rhein on the regulation of epigenetic modification and its underlying mechanisms, which involve the regulation of DNA methylation, protein acetylation, and RNA methylation, so as to provide a basis for the development and application of rhein.

Solvothermal Synthesis of Novel Magnetic Nickel Based Iron Oxide Nanocomposites for Selective Capture of Global- and Mono-Phosphopeptides.

A facile solvothermal method was developed for synthesis of magnetic nickel-based iron oxide nanocomposites (MNFOs) with different ratios of Ni2+ to Fe3+ for different reaction time. Two factors including dosage of Ni source and length of reaction were investigated for influence on the morphology and composition of MNFOs, as well as their distinct selectivity for different phosphopeptides. After thorough characterization, the possible formation mechanism of MNFOs was proposed. Very interestingly, MNFOs with Ni2+/Fe3+ ratios of 4:5 prepared for 8 h (MNFO-S) and for 24 h (MNFO-L) can selectively capture global- and monophosphopeptides at the fmol level with excellent enrichment performance. These two affinity probes have been exploited to isolate and enrich the phosphopeptides from human normal hepatic cells HL 7702 after exposure to atmospheric fine particulates (PM2.1), which revealed that the protein phosphorylation level was increased significantly in cells after stimulation by fine particulate matters. The findings could provide a new insight for the nickel-based affinity protocol to analyze the mutation of phosphopeptides during cellular signaling pathways in response to exogenous environment stimulation. Consequently, this present work proposed a promising strategy to isolate monophosphopeptides from global phosphopeptides for phosphoproteome research.

A small molecule transcription factor EB activator ameliorates beta-amyloid precursor protein and Tau pathology in Alzheimer's disease models.

Accumulating studies have suggested that targeting transcription factor EB (TFEB), an essential regulator of autophagy-lysosomal pathway (ALP), is promising for the treatment of neurodegenerative disorders, including Alzheimer's disease (AD). However, potent and specific small molecule TFEB activators are not available at present. Previously, we identified a novel TFEB activator named curcumin analog C1 which directly binds to and activates TFEB. In this study, we systematically investigated the efficacy of curcumin analog C1 in three AD animal models that represent beta-amyloid precursor protein (APP) pathology (5xFAD mice), tauopathy (P301S mice) and the APP/Tau combined pathology (3xTg-AD mice). We found that C1 efficiently activated TFEB, enhanced autophagy and lysosomal activity, and reduced APP, APP C-terminal fragments (CTF-ß/α), ß-amyloid peptides and Tau aggregates in these models accompanied by improved synaptic and cognitive function. Knockdown of TFEB and inhibition of lysosomal activity significantly inhibited the effects of C1 on APP and Tau degradation in vitro. In summary, curcumin analog C1 is a potent TFEB activator with promise for the prevention or treatment of AD.

Primary hypoparathyroidism accompanied by rhabdomyolysis induced by infection: A case report.

BACKGROUND: Primary hypoparathyroidism (HPT) is rarely seen in the clinic, and it can be combined with rhabdomyolysis. There are few reports about this phenomenon. Therefore, it is significant to explore the etiology that is conducive to early diagnosis, timely treatment, and preventing the recurrence. CASE SUMMARY: A 63-year-old man was admitted to our hospital with a severe upper respiratory tract infection and progressing decreased myodynamia of the lower limbs. Blood tests showed creatine kinase > 32000 U/L, creatinine 207.8 µmol/L, calcium 1.28 mmol/L, myoglobin 558.7 ng/mL, and parathyroid hormone 0 pg/mL. He was diagnosed with primary HPT with rhabdomyolysis, and severe upper respiratory tract infection was considered to be the initial trigger. He responded well to supplementation of intravenous calcium gluconate and oral calcium as well as bedside hemodialysis, fluid hydration, infection control, protecting the liver, etc. Creatine kinase, myoglobin, and serum calcium returned to normal, and muscle strength improved significantly. Symptoms improved after symptomatic treatment. CONCLUSION: Severe infection should be prevented, which is the key cause of rhabdomyolysis in patients with HPT.

Acupuncture plus Chinese Herbal Medicine for Irritable Bowel Syndrome with Diarrhea: A Systematic Review and Meta-Analysis.

PURPOSE: To comprehensively evaluate the efficacy and safety of acupuncture combined with Chinese herbal medicine (CHM) in treating irritable bowel syndrome with diarrhea (IBS-D). METHODS: Relevant randomized controlled trials (RCTs) were systemically retrieved from electronic databases from inception to March 2018, including the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, EMBASE, China National Knowledge Infrastructure (CNKI), Chinese Biological Medical Database (CBM, SinoMed), China Science and Technology Journal Database (VIP), and Wan Fang Data. Meanwhile, pooled estimates, including the 95% confidence interval (CI), were calculated for primary and secondary outcomes of IBS-D patients. Besides, quality of relevant articles was evaluated using the Cochrane Collaboration's risk of bias tool, and the Review Manager 5.3 and Stata12.0 softwares were employed for analyses. RESULTS: A total of 21 RCTs related to IBS-D were included into this meta-analysis. Specifically, the pooled results indicated that (1) acupuncture combined with CHM might result in more favorable improvements compared with the control group (relative risk [RR] 1.29; 95% CI 1.24-1.35; P =0.03); (2) the combined method could markedly enhance the clinical efficacy in the meantime of remarkably reducing the scores of abdominal pain (standardized mean difference [SMD] -0.45; 95% CI -0.72, -0.17; P = 0.002), abdominal distention/discomfort (SMD -0.36; 95% CI -0.71, -0.01; P = 0.04), diarrhea (SMD -0.97; 95% CI -1.18, -0.75; P < 0.00001), diet condition (SMD -0.73; 95% CI -0.93, -0.52; P<0.00001), physical strength (SMD -1.25; 95% CI -2.32, -0.19; P = 0.02), and sleep quality (SMD -1.02; 95% CI -1.26, -0.77; P < 0.00001) compared with those in the matched groups treated with western medicine, or western medicine combined with CHM. Additionally, a metaregression analysis was constructed according to the name of prescription, acupuncture type, treatment course and publication year, and subgroup analyses stratified based on the names of prescriptions and acupoints location were also carried out, so as to explore the potential heterogeneities; and (3) IBS-D patients treated with the combined method only developed inconspicuous adverse events; more importantly, the combined treatment had displayed promising long-term efficacy. CONCLUSIONS: Findings in this study indicate that acupuncture combined with CHM is suggestive of an effective and safe treatment approach for IBS-D patients, which may serve as a promising method to treat IBS-D in practical application. However, more large-scale, multicenter, long-term, and high-quality RCTs are required in the future, given the small size, low quality, and high risk of the studies identified in this meta-analysis.

[Research progress on therapeutic targets of active components in Chinese herbs for treatment of nonalcoholic fatty liver disease].

Nonalcoholic fatty liver disease(NAFLD) is a kind of metabolic liver injury, which is closely associated with insulin resistance and genetic susceptibility. Traditional Chinese herbs used in the treatment of nonalcoholic fatty liver disease are widely investigated in recent years. A series of recent studies show that the effects of the active components in traditional Chinese herbs on NAFLD are associated with activating AMPK signaling pathway, improving insulin resistance, modulating the activity and expression of peroxisome proliferator-activated receptor γ, antioxidant and anti-inflammatory activities and regulating intestinal flora. In this review, the potential therapeutic targets of the active components from traditional Chinese herbs for NAFLD would be summarized to provide a new thought for further research and clinical treatment of nonalcoholic fatty liver disease.

[Ginsenoside Rb1 upregulates expressions of GLUTs to promote glucose consumption in adiopcytes].

Previous studies have shown that ginsenoside Rb1 (Rb1), one of active components in ginseng, can activate insulin signaling pathway and promote translocation of glucose transporters (GLUTs) to increase glucose uptake in adipocytes. However, the effect of Rb1 on the expressions of GLUTs remains unknown. In this study, the effects of Rb1 on GLUT1 and GLUT4 were observed in 3T3-L1 adipocytes and epididymal adipose tissue of db/db obese diabetic mice. Male db/db mice were treated with Rb1 by intraperitoneal injection at the dosage of 20 mg x kg(-1) for 14 d. Rb1 reduced HOMA-IR significantly (P < 0.05, n = 5), and FBG and FINS sowed declining trend after treatment with Rb1. Rb1 recovered the expressions of GLUT1 and GLUT4 and phosphorylation of AKT in adipose tissue of db/db mice. In vitro, glucose consumption in 3T3-L1 adipocytes treated with 10 micromol x L(-1) Rb1 for 24 h was elevated (P < 0.05, n=3), and mRNA of GLUT1 and GLUT4 were up-regulated (P < 0.05, n=3) and proteins of GLUT1 and GLUT4 were also increased. AKT was activated in adipocytes treated with Rb1 for 3 h. It can be concluded that ginsenoside Rb1 can up-regulate the expression of GLUTs in adipose tissue, in addition to activate insulin signalling pathway, which may partially account for its insulin sensitizing activity and regulating effect of glucose metabolism.

[Effect of ginsenoside Rb1 in ameliorating insulin resistance and ectopic fat deposition in obese mice induced by high fat diet].

Ginsenoside Rb1 is an active component in ginseng. Previous in vitro experiments showed that ginsenoside Rb1, could inhibit lipolysis and promote glucose transporter in adipocytes. This study focused on the effect of ginsenoside Rb1 in insulin resistance and ectopic fat deposit in obese mice induced by high fat diet and its molecular mechanism. Obese male C57/L mice induced by high fat diet were randomly divided into the diet-induced obesity group (DIO group), the ginsenoside Rb1 group (Rb1 group) and the rosiglitazone group (Rog group), and continuously fed with high fat diet. In addition, male C57/L mice fed with normal diet were selected as the normal group (NC group). Mice in Rb1 group and Rog groups were intraperitoneally injected with ginsenoside Rb1 and rosiglitazone with the dosage of 20 mg x kg(-1) and 10 mg x kg(-1), respectively. NC and DIO groups were intraperitoneally injected with the same amount of saline. Two weeks later, the intraperitoneal glucose tolerance test (IPGTT) was performed. Three days later, the mice were killed, and their serum samples were collected to detect insulin and free fatty acid (FFA). Their livers were weighed to examine the triglyceride content, and a pathological detection was performed. Epididymal adipose tissues were weighed, and PDE3B, HSL and perilipin were detected by Western blotting. The results showed that the treatment with ginsenoside Rb1 for two weeks could improve the glucose tolerance of obese mice. Except for 0-120 min, the areas under the glucose tolerance curve (0-30 min, 0-60 min and 0-90 min) in the Rb1 group were less than that in the DIO group (P < 0.05, n = 5), with a much lower HOMA-IR (P < 0.05, n = 5). The fat level of obese mice was significantly reduced by Rbl (P < 0.05, n = 5), and so were liver weight/weight (P < 0.05, n = 8). The increased serum FFA of obese mice declined after the treatment of Rb1 (P < 0.05, n = 8). Rb1 could partially recover the expression of perilipin in adipose tissues, but without obvious change in the expressions of PDE3B and HSL and the phosphorylated activation. The above findings indicated that ginsenoside Rb1 could reduce the release of FFA and alleviate the ectopic deposit of triglyceride by up-regulating the expression of perilipin in adipose tissue, which may be one of its mechanisms for improving the insulin resistance and abnormal glucose metabolism of organisms.

Pretreatment with the total flavone glycosides of Flos Abelmoschus manihot and hyperoside prevents glomerular podocyte apoptosis in streptozotocin-induced diabetic nephropathy.

Diabetic nephropathy (DN) is an important diabetic complication, and podocyte apoptosis plays a critical role in the development of DN. In the present study, we examined the preventive effect of the total flavone glycosides of Flos Abelmoschus manihot (TFA) on urinary microalbumin and glomerular podocyte apoptosis in experimental DN rats. The preliminary oral administration of TFA (200 mg/kg/day) for 24 weeks significantly decreased the urinary microalbumin to creatinine ratio and 24-h urinary total protein in streptozotocin-induced DN rats. Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay indicated glomerular cell apoptosis in DN rats was significantly improved by pretreatment with TFA. Furthermore, fluorescence-activated cell sorting and Hoechst 33342 staining suggested preincubation with hyperoside (50 and 200 µg/mL), the major active constituent of TFA, could significantly mitigate cultured podocyte apoptosis induced by the advanced glycation end-products (AGEs). Western blot analysis showed that increased caspase-3 and caspase-8 expressions induced by AGEs were also inhibited by pretreatment with hyperoside at both doses. Our results demonstrate that TFA pretreatment can decrease urinary albumin excretion in early-stage DN, which might be accomplished by preventing renal damage and podocyte apoptosis.