Elucidation of the anti-ß-cell dedifferentiation mechanism of a modified Da Chaihu Decoction by an integrative approach of network pharmacology and experimental verification.

ETHNOPHARMACOLOGICAL RELEVANCE: Modified Da Chaihu decoction (MDCH) is a traditional Chinese herbal prescription that has been used in the clinic to treat type 2 diabetes (T2D). Previous studies have confirmed that MDCH improves glycemic and lipid metabolism, enhances pancreatic function, and alleviates insulin resistance in patients with T2D and diabetic rats. Evidence has demonstrated that MDCH protects pancreatic ß cells via regulating the gene expression of sirtuin 1 (SIRT1) and forkhead box protein O1 (FOXO1). However, the detailed mechanism remains unclear. AIM OF THE STUDY: Dedifferentiation of pancreatic ß cells mediated by FOXO1 has been recognized as the main pathogenesis of T2D. This study aims to investigate the therapeutic effects of MDCH on T2D in vitro and in vivo to elucidate the potential molecular mechanisms. MATERIALS AND METHODS: To predict the key targets of MDCH in treating T2D, network pharmacology methods were used. A T2D model was induced in diet-induced obese (DIO) C57BL/6 mice with a single intraperitoneal injection of streptozotocin. Glucose metabolism indicators (oral glucose tolerance test, insulin tolerance test), lipid metabolism indicators (total cholesterol, triglyceride, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol), inflammatory factors (C-reactive protein, interleukin 6, tumor necrosis factor alpha), oxidative stress indicators (total antioxidant capacity, superoxide dismutase, malondialdehyde), and hematoxylin and eosin staining were analyzed to evaluate the therapeutic effect of MDCH on T2D. Immunofluorescence staining and quantification of FOXO1, pancreatic and duodenal homeobox 1 (PDX1), NK6 homeobox 1 (NKX6.1), octamer-binding protein 4 (OCT4), neurogenin 3 (Ngn3), insulin, and SIRT1, and Western blot analysis of insulin, SIRT1, and FOXO1 were performed to investigate the mechanism by which MDCH inhibited pancreatic ß-cell dedifferentiation. RESULTS: The chemical ingredients identified in MDCH were predicted to be important for signaling pathways related to lipid metabolism and insulin resistance, including lipids in atherosclerosis, the advanced glycation end product receptor of the advanced glycation end product signaling pathway, and the FOXO signaling pathway. Experimental studies showed that MDCH improved glucose and lipid metabolism in T2D mice, alleviated inflammation and oxidative stress damage, and reduced pancreatic pathological damage. Furthermore, MDCH upregulated the expression levels of SIRT1, FOXO1, PDX1, and NKX6.1, while downregulating the expression levels of OCT4 and Ngn3, which indicated that MDCH inhibited pancreatic dedifferentiation of ß cells. CONCLUSIONS: MDCH has therapeutic effects on T2D, through regulating the SIRT1/FOXO1 signaling pathway to inhibit pancreatic ß-cell dedifferentiation, which has not been reported previously.

Quercetin prevents the ferroptosis of OPCs by inhibiting the Id2/transferrin pathway.

Spinal cord injury (SCI) is a destructive neurological disorder that causes impaired mobility, sensory, and autonomic dysfunctions. The loss of oligodendrocyte progenitor cells (OPCs), which can differentiate into mature oligodendrocytes and re-myelinate damaged axons, is related to poorer recovery for SCI patients. However, inhibiting OPCs loss has always been a difficult problem to overcome. In this study, we demonstrated the anti-ferroptosis effects of quercetin as a mechanism in erastin-induced OPC ferroptosis. Quercetin ameliorated erastin-induced ferroptosis in OPCs, as indicated by decreased iron concentration, reactive oxygen species (ROS) production, and increased content of glutathione (GSH) as well as more normal mitochondria morphology. Compared with erastin-induced OPCs, the myelin basic protein (MBP)-positive myelin and NF200-positive axonal was remarkably increased in quercetin-treated OPCs. Furthermore, quercetin ameliorated the erastin-induced ferroptosis as well as the myelin and axon loss of OPCs by downregulating transferrin. Transfected OPCs with transferrin overexpression plasmids significantly abrogated the protective role of quercetin in OPC ferroptosis. Using ChIP-qPCR, a direct interaction of transferrin with its upstream gene Id2 was found. The overexpression of Id2 reversed the effect of quercetin on OPC ferroptosis. In vivo study found that quercetin greatly decreased the area of injury, and enhanced the BBB score after SCI. Furthermore, in the SCI model, quercetin significantly downregulated Id2 and transferrin expression, while significantly up-regulated GPX4 and PTGS2 expression. In conclusion, quercetin prevents the ferroptosis of OPCs by inhibiting the Id2/transferrin pathway. These findings highlight quercetin as an anti-ferroptosis agent for the treatment or prevention of spinal cord injury.

CircVAPA contributes to hyper-proliferation and inflammation of keratinocytes through miR-125b-5p/sirt6 axis in psoriasis.

Psoriasis is an autoimmune skin disease with abnormal keratinocyte hyperproliferation. The important roles of circular RNAs (circRNAs) in various inflammatory diseases have been revealed. The present study aimed to investigate the roles of circVAPA and its molecular mechanisms in psoriasis. Quantitative real-time polymerase chain reaction was performed to measure the RNA expression. Enzyme-linked immunosorbent assays were employed to examine the production of inflammatory factors. Cell-counting kit-8, EDU and flow cytometry assay were conducted to examine the cell viability, proliferation and apoptosis respectively. Dual-luciferase reporter assay and ribonucleoprotein immunoprecipitation (RIP) were conducted to verify the target relationship between miR-125b-5p and circVAPA or Sirt6. Herein our findings showed increased expression of circVAPA and Sirt6 and decreased level of miR-125b-5p in psoriatic lesional tissues and M5-stimulated keratinocytes. Mechanistically, circVAPA knockdown significantly suppressed the promotion of M5 on cell viability, proliferation, and inflammation of HaCaT cells. circVAPA was verified to interact with miR-125b-5p, while inhibition of miR-125b-5p counteracted circVAPA knockdown-mediated effects in M5-stimulated HaCaT cells. Sirt6 was confirmed as a target of miR-125b-5p, and miR-125b-5p overexpression inhibited cell growth and inflammation partly by targeting Sirt6 in M5-stimulated HaCaT cells. Moreover, circVAPA was featured as a competing endogenous RNA by directly sponging miR-125b-5p to up-regulate the expression of Sirt6. CircVAPA participate in the progression of psoriasis through miR-125b-5p/sirt6 axis by regulating proliferation and inflammation of keratinocytes, highlighting a potential therapeutic target for psoriasis.

Excess dietary zinc drives a Cushing's-like syndrome in ovariectomized mice - Implications for postmenopausal obesity.

Postmenopausal women have an increased risk of obesity, but the underlying cause is not clear. We unexpectedly found that excess dietary zinc induced severe obesity and a Cushing's-like syndrome without increased food intake in ovariectomized (Ovx) but not in sham-operated mice. Zinc accumulated in the adrenal glands and inhibited adrenal 17,20-lyase activity and steroid synthesis. As adrenal steroids are the only source of estrogen in Ovx mice, estrogen deficiency induced adrenal hyperplasia, glucocorticoid overproduction, and consequent development of a Cushing's-like syndrome. Adrenal steroid supplementation prevented the effects of zinc. Plasma zinc was positively correlated with cortisol level and negatively correlated with the levels of adrenal steroids and estrogen in obese postmenopausal women. The finding of a link between dietary zinc, estrogen deficiency, and postmenopausal obesity, implies that postmenopausal obesity might be prevented by supplementation with a adrenal steroid and avoiding excess dietary zinc.

The Effect of Berberine on Metabolic Profiles in Type 2 Diabetic Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: Rhizoma Coptidis is an herb that has been frequently used in many traditional formulas for the treatment of diabetic mellitus (DM) over thousands of years. Berberine, the main active component of Rhizoma Coptidis, has been demonstrated to have the potential effect of hypoglycemia. To determine the potential advantages of berberine for diabetic care, we conducted this systematic review and meta-analysis to examine the efficacy and safety of berberine in the treatment of patients with type 2 DM. METHODS: Eight databases including PubMed, Embase, Web of Science, the Cochrane library, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Database (SinoMed), Wanfang Database, and Chinese VIP Information was searched for randomized controlled trials (RCTs) reporting clinical data regarding the use of berberine for the treatment of DM. Publication qualities were also considered to augment the credibility of the evidence. Glycemic metabolisms were the main factors studied, including glycosylated hemoglobin (HbA1c), fasting plasm glucose (FPG), and 2-hour postprandial blood glucose (2hPG). Insulin resistance was estimated by fasting blood insulin (FINS), homeostasis model assessment-insulin resistance (HOMA-IR), and body mass index (BMI). Lipid profiles were also assessed, including triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL), and high-density lipoprotein (HDL), along with inflammation factors such as C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). Serum creatinine (Scr), blood urea nitrogen (BUN), and adverse events were applied to evaluate the safety of berberine. RESULTS: Forty-six trials were assessed. Analysis of berberine applied alone or with standard diabetic therapies versus the control group revealed significant reductions in HbA1c (MD = -0.73; 95% CI (-0.97, -0.51)), FPG (MD = -0.86, 95% CI (-1.10, -0.62)), and 2hPG (MD = -1.26, 95% CI (-1.64, -0.89)). Improved insulin resistance was assessed by lowering FINS (MD = -2.05, 95% CI (-2.62, -1.48)), HOMA-IR (MD = -0.71, 95% CI (-1.03, -0.39)), and BMI (MD = -1.07, 95% CI (-1.76, -0.37)). Lipid metabolisms were also ameliorated via the reduction of TG (MD = -0.5, 95% CI (-0.61, -0.39)), TC (MD = 0.64, 95% CI (-0.78, -0.49)), and LDL (MD = 0.86, 95% CI (-1.06, -0.65)) and the upregulation of HDL (MD = 0.17, 95% CI (0.09, 0.25)). Additionally, berberine improved the inflammation factor. CONCLUSION: There is strong evidence supporting the clinical efficacy and safety of berberine in the treatment of DM, especially as an adjunctive therapy. In the future, this may be used to guide targeted clinical use of berberine and the development of medications seeking to treat patients with T2DM and dyslipidemia.

Quercetin promotes locomotor function recovery and axonal regeneration through induction of autophagy after spinal cord injury.

Quercetin (Que), one of the flavonoids, exerts numerous actions on the central nervous system. However, the roles and underlying mechanism of Que in locomotor function recovery and axonal regeneration following spinal cord injury (SCI) have not been fully elucidated. A rat model of spinal cord injury (SCI) was established at T10 using the modified Allen's method. The results in our study indicated that Basso, Beattie and Bresnahan (BBB) locomotor scores were significantly higher after Que treatment. Additionally, Que administration cut down the latency of somatosensory evoked potentials (SEP) and motor evoked potentials (MEP), increased the amplitude of MEP and SEP following SCI. Hematoxylin-eosin (HE) staining demonstrated that Que administration reduced lesion size and cavity formation. Biotinylated dextran amine (BDA) anterograde tracing revealed that BDA positive fibres were increased by Que following SCI. Immunofluorescence staining revealed that Que elevated 5-hydroxytryptamine (5-HT) positive nerve fibres and neurofilament-200 (NF-200) positive neurons, reduced glial fibrillary acidic protein (GFAP) positive astrocytes. In addition, Que inhibited GFAP expression, increased both NeuN and NF-200 expression and facilitated the spinal cord energy metabolism. Moreover, Que increased 18 F-FDG uptake in a time-dependent manner. Furthermore, Que increased Beclin 1 and LC3 II expression, blocked the phosphorylation of Akt, mTOR and p70S6K. 3-methyladenine (3-MA) partly abolished the neuro-protective roles of Que following SCI. Taken together, our study suggested that Que might promote locomotor function recovery, axonal regeneration and energy metabolism through induction of autophagy via Akt/mTOR/p70S6K pathway.

Baduanjin exerts anti-diabetic and anti-depression effects by regulating the expression of mRNA, lncRNA, and circRNA.

BACKGROUND: Baduanjin, a traditional Chinese exercise therapy, has been widely used in China to treat type 2 diabetes (T2DM) with depression (DD). However, the underlying mechanism of Baduanjin in anti-DD is unclear. This study was focused on investigating the effects of Baduanjin on symptoms of depression and blood glucose in patients with DD and the underlying mechanism. METHODS: We performed a 12-week Baduanjin intervention on patients with DD and longitudinally compared the differential expressions of lncRNAs, circRNAs, and mRNAs between pre- (BDD) and post- (ADD) Baduanjin intervention in the same group. Subsequently, Gene Ontology (GO) and pathway analysis was performed to investigate the function of differentially expressed mRNAs. Finally, Reverse Transcription-Polymerase Chain Reaction (RT-PCR) was used to verify the sequencing result and the mRNA-lncRNA regulatory network was constructed. RESULTS: The blood glucose level, depression index scores, and PHQ9 scores of the patients with DD were significantly decreased (P < 0.05) after Baduanjin intervention. Compared to BDD, 207 lncRNAs, 266 circRNAs, and 610 differentially expressed mRNAs were identified in ADD. Kyoto Encyclopedia of Genes and Genomes (KEGG) and GO showed that the significantly dysregulated mRNAs were mainly involved in immune function and inflammatory response pathways, and various signaling pathways including IL-17 and TNF. In addition, we selected five differentially expressed lncRNAs to construct an lncRNA-mRNA regulatory network, and found a total of 1045 mRNAs associated with them. CONCLUSIONS: Our research is the first systematic profiling of mRNA, lncRNA, and circRNA in patients of ADD and BDD, and provides valuable insights in the potential mechanism of Baduanjin in anti-DD. Further, it was confirmed that Baduanjin is a safe and effective intervention for patients with DD because it can effectively ameliorate the symptoms of depression and blood glucose levels in patients with DD by regulating the dysregulated expression of lncRNA, mRNA, and circRNA.

Early Out-of-Bed Functional Exercise Benefits Elderly Patients Following Hip Fracture: A Retrospective Cohort Study.

Hip fracture is a worldwide medical problem with devastating consequences. Older adults are at higher risk for complications and have more mobility limitation. The aim of this study was to assess the impact of delay in out-of-bed functional exercise on one-year mortality and functional outcomes for elderly patients with hip fracture in China. 1,022 cases of patients with hip fracture who were older than 75 were involved in this retrospective cohort study between 2007 and 2017. One-year mortality, follow up Activities of Daily Living (ADL) score, and Harris hip score were collected. Patients with hip fracture experienced an average of 2.9 days of in-bed functional exercise, 41.4% (n = 423) taken out-of-bed functional exercise within 2 days. A Cox proportional regression model showed that after adjustment for age, sex, cardiovascular disease, and urinary disease, delayed out-of-bed functional exercise (> 2 days) associated with higher one-year mortality (OR = 1.38, 95% confidence interval [CI]: 1.09 to 1.69). Ordinary least squares regression showed that delayed out-of-bed functional exercise associated with worsen ADL scores at 1-month (difference of -3.9 points, 95% CI: -6.4 to -1.7), although the long term ADL scores did not have increased. In addition, there were no associations between out-of-bed functional exercise timing and the Harris hip score at 12 months. In conclusion, in elderly patients with hip fracture in China, delayed out-of-bed functional exercise was not associated with improved Harris hip score, but it was associated with worsen ADL capacities at 1-month postoperatively and higher one-year mortality. The present study emphasizes the benefit of early out-of-bed exercise on the majority of elderly patients with hip fracture.

Bone and plasma citrate is reduced in osteoporosis.

High concentration of citrate exists in bone of humans and all osteo-vertebrates, and citrate incorporation imparts important biomechanical and other functional properties to bone. However, which cells are responsible for citrate production in bone remains unclear and whether the citrate component changes with bone loss during osteoporosis is also not known. Here, we show that the citrate content is markedly reduced in the bone of mice or rats with age-related, ovariectomy-induced or retinoic acid-induced bone loss. Plasmic citrate is also downregulated in osteoporotic animals. Importantly, the plasmic citrate level of aged osteoporotic males is significantly lower than that of young healthy males and positively correlates with human lumbar spine bone mineral density (BMD) and total hip BMD. Furthermore, citrate production increases with in vitro osteoblastic differentiation, accompanied by upregulation of proteins involved in citrate secretion, suggesting that osteoblasts are highly specialized cells that produce citrate in bone. Our findings establish a novel relationship between citrate content and bone loss-related diseases such as osteoporosis, suggesting a critical role of bone citrate in the maintenance of the citrate balance in the circulation. Serum citrate level may thus represent a novel marker for osteoporosis.

Chinese herbal medicine Shenzhuo Formula treatment in patients with macroalbuminuria secondary to diabetic kidney disease: study protocol for a randomized controlled trial.

BACKGROUND: Diabetic kidney disease (DKD) is a serious complication associated with diabetes mellitus and can cause end-stage renal disease (ESRD). Traditional Chinese medicine (TCM) is widely used in China to treat DKD, and in particular microalbuminuria and macroalbuminuria. This study will address the efficacy and safety of Shenzhuo Formula (SZF), a frequently prescribed TCM, in DKD patients with macroalbuminuria. METHODS/DESIGN: This study is a 24-week, randomized, multi-center, double-blinded, double-dummy, controlled, clinical trial that will include 120 DKD patients aged 18 to 80 years old with a 24-h urinary protein (24-h UP) level of between 0.5 g and 3 g and serum creatinine (SCr) ≤ 133 µmol/L (1.5 mg/dL) and compare SZF to irbesartan. The 24-h UP change from baseline to week 24 will represent the primary endpoint with secondary endpoints including SCr, estimated glomerular filtration rate (eGFR), TCM symptoms, urinary albumin excretion rate (UAER), etc. Safety assessments will also be evaluated. DISCUSSION: This study will provide initial evidence regarding the efficacy and safety of SZF relative to irbesartan in the treatment of DKD patients with macroalbuminuria. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ID: ChiCTR-ICR-15006311 . Registered on 15 April 2015.

Retrospective analysis of the overt proteinuria diabetic kidney disease in the treatment of modified Shenzhuo formula for 2 years.

The objective of the present study was to evaluate the 2-year effectiveness of modified Shenzhuo formula in the treatment of overt proteinuria diabetic kidney disease (DKD).Patients diagnosed with type 2 DKD in the clinical research database of Prof Xiaolin Tong (>20,000 data points) with >1-year follow-up were screened for this study. Patients' demographic data, chief complaint, present illness, past history, allergic history, personal history, family history, test results, tongue images, pulse information, and prescription information at 1, 1.5, and 2 years of follow-up were analyzed. EpiData3.1 was used to establish the electronic database of this research and SPSS v20.0 (SPSS Inc, Chicago, IL) was used for performing statistical analyses.The patients' common main symptoms of overt proteinuria DKD were weak breath and fatigue, numbness of limbs, insomnia, blurred vision, nocturia, edema, low backache, constipation, itchy skin ulcer, and chills. The average 24-hour urinary protein of patients treated with modified Shenzhuo formula was statistically significantly lower than baseline values at 1, 1.5, and 2 years (0.66 g, 95% confidence interval [CI] [-0.95, -0.41]; 1.00 g, 95% CI [-1.67, 0.38]; 1.11 g, 95% CI [-1.79, -0.57]). There are no statistically significant differences between the glomerular filtration rate at the baseline and that after modified Shenzhuo formula intervention. Statistically significant reductions in serum triglyceride and glycosylated hemoglobin values and systolic blood pressure also were recorded. Other indexes, including serum creatinine, blood urea nitrogen, diastolic blood pressure, cholesterol, high-density lipoprotein, and low-density lipoproteins, did not differ between baseline and post-treatment time points.Modified Shenzhuo formula could reduce 24-hour urinary protein excretion in patients with DKD. The formula maybe had the potential advantages on glomerular filtration rate, creatinine reciprocal, blood lipid levels, etc.

Diabetic kidney disease treated with a modified Shenzhuo formula derived from Traditional Chinese Medicine: a case report.

INTRODUCTION: Diabetic kidney disease (DKD) is one of the most common microvascular complications of diabetes mellitus and is the leading cause of end-stage renal disease. DKD seriously affects the quality of life of patients and brings heavy economic burden to the country. At present, the pathogenesis of DKD is not entirely clear, and clinical treatment is mainly to control blood glucose and lower blood pressure and urine protein. However, the clinical effect is not satisfactory. CASE PRESENTATION: A female patient, aged 72 years, first visited our hospital endocrinology clinic, and was diagnosed with DKD. She suffered from fatigue, cold sensation in the lower extremities, convulsion of the lower limbs and frequent urination at night. She had a dark purple tongue with white and yellow fur and sublingual varices. Accessory examinations showed that her fasting blood glucose was 5.7 mmol/L, serum creatinine 159 µmol/L, blood urea nitrogen 13.6 µmol/L, blood uric acid 493 µmol/L, and blood pressure 138/65 mm Hg. The patient received Traditional Chinese Medicine treatment of the modified Shenzhuo formula [Huangqi (Radix Astragali Mongolici), Dahuang (Radix Et Rhizoma Rhei Palmati), Shuizhi (Hirudo) and Danshen (Radix Salviae Miltiorrhizae)] for 7 years and achieved good results. CONCLUSION: This case provides a specific treatment plan and an effective reference for clinical application of Traditional Chinese Medicine for treating DKD. This may be an alternative treatment for DKD.

Osteoblasts secrete Cxcl9 to regulate angiogenesis in bone.

Communication between osteoblasts and endothelial cells (ECs) is essential for bone turnover, but the molecular mechanisms of such communication are not well defined. Here we identify Cxcl9 as an angiostatic factor secreted by osteoblasts in the bone marrow microenvironment. We show that Cxcl9 produced by osteoblasts interacts with vascular endothelial growth factor and prevents its binding to ECs and osteoblasts, thus abrogating angiogenesis and osteogenesis both in mouse bone and in vitro. The mechanistic target of rapamycin complex 1 activates Cxcl9 expression by transcriptional upregulation of STAT1 and increases binding of STAT1 to the Cxcl9 promoter in osteoblasts. These findings reveal the essential role of osteoblast-produced Cxcl9 in angiogenesis and osteogenesis in bone, and Cxcl9 can be targeted to elevate bone angiogenesis and prevent bone loss-related diseases.

Assessment of the Reporting Quality of Placebo-controlled Randomized Trials on the Treatment of Type 2 Diabetes With Traditional Chinese Medicine in Mainland China: A PRISMA-Compliant Systematic Review.

Placebo-controlled randomized trials are often used to evaluate the absolute effect of new treatments and are considered gold standard for clinical trials. No studies, however, have yet been conducted evaluating the reporting quality of placebo-controlled randomized trials. The current study aims to assess the reporting quality of placebo-controlled randomized trials on treatment of diabetes with Traditional Chinese Medicine (TCM) in Mainland China and to provide recommendations for improvements.China National Knowledge Infrastructure database, Wanfang database, China Biology Medicine database, and VIP database were searched for placebo-controlled randomized trials on treatment of diabetes with TCM. Review, animal experiment, and randomized controlled trials without placebo control were excluded. According to Consolidated Standards of Reporting Trials (CONSORT) 2010 checklists items, each item was given a yes or no depending on whether it was reported or not.A total of 68 articles were included. The reporting percentage in each article ranged from 24.3% to 73%, and 30.9% articles reported more than 50% of the items. Seven of the 37 items were reported more than 90% of the items, whereas 7 items were not mentioned at all. The average reporting for "title and abstract," "introduction," "methods," "results," "discussion," and "other information" was 43.4%, 78.7%, 40.1%, 49.9%, 71.1%, and 17.2%, respectively. The percentage of each section had increased after 2010. In addition, the reporting of multiple study centers, funding, placebo species, informed consent forms, and ethical approvals were 14.7%, 50%, 36.85%, 33.8%, and 4.4%, respectively.Although a scoring system was created according to the CONSORT 2010 checklist, it was not designed as an assessment tool. According to CONSORT 2010, the reporting quality of placebo-controlled randomized trials on the treatment of diabetes with TCM improved after 2010. Future improvements, however, are still needed, particularly in methods sections.

Application of Herbal Medicines with Bitter Flavor and Cold Property on Treating Diabetes Mellitus.

Diabetes mellitus has been a global pandemic. Traditional Chinese Medicine has been used on diabetes mellitus for thousands of years and the modern Chinese medicine studies have found a curative effect of herbal medicine with bitter flavor and cold property on diabetes. This review will introduce the theory summary of flavor and property in TCM, argument basis, the evidences from clinical trails and animal experiments, the possible antidiabetic mechanisms, and advantages on lowering glucose of herbal medicines with bitter flavor and cold property and take rhizome, Chinese rhubarb, and Momordica charantia, the three herbal medicines with bitter flavor and cold property, as examples to illustrate the exact antidiabetic effect. It is hoped that this review can provide some ideas and inspiration for the treatment of diabetes with herbal medicine.

Innovative Thoughts on Treating Diabetes from the Perspective of Traditional Chinese Medicine.

The rapidly increasing incidence of diabetes mellitus (DM) is becoming a major public health issue. As one of the important parts in complementary and alternative therapies, traditional Chinese medicine (TCM) is promising in treating DM. In this review, we summarize new thoughts on treating DM that aim to improve the clinical efficacy of TCM from the perspectives of principle, methods, formula, herbs, and doses. Our approach is as follows: principle: we use a combination of symptoms, syndromes, and diseases as a new mode for treating diabetes; methods: emphasizing heat-clearing in the early and middle stage of T2DM and invigorating blood circulation throughout the whole process of T2DM are two innovative methods to treat T2DM; formulas and herbs: choosing formulas and herbs based on the combination of TCM theory and current medicine. We will emphasize four strategies to help doctors choose formulas and herbs, including treatment based on syndrome differentiation, choosing herbs of bitter and sour flavors to counteract sweet flavor, choosing formulas and herbs aimed at main symptoms, and using modern pharmacological achievements in clinical practice; dose: reasonable drug dose plays an important role in the treatment of DM and a close relationship exists between dose and clinical efficacy.

[Systematic review of efficacy and safety of shenmai injection for chronic heart failure].

The paper is to evaluate the efficacy and safety of Shenmai injection for chronic heart failure, retrieving the Pubmed, CBM, CNKI, Wanfang database and VIP database to comprehensively collect all types research report of Shenmai injection for chronic heart failure (CHF). Particularly wishing to point out, randomized controlled trials are include for the evaluation of effectiveness, which are statistically analyzed and evaluated by Rev-Man 5. 2. The current studies show that the improvement rate of NYHA classification of cardiac function of CHF patients and their related indexes figure such as LVEF, SV, CO, BNP, 6 min walking test value are all improved by the combination of Shenmai injection and foundation treatment. However, HR is almost no improvement. Meanwhile, serious ADR/AE of Shenmai injection for CHF isn't appear.

A monoclonal antibody against PMEL.

PMEL, also known as Pmel17 or gp100, is a melanocyte-specific glycoprotein that is essential for the formation of stage II melanosomes. As it has a highly restricted expression pattern in normal tissues and a transient presence on the cell surface, PMEL is believed to be a potential target for antibody drug conjugate therapy in some pigmentary diseases. The production of a high specificity and high affinity monoclonal antibody against human PMEL was helpful for the antibody drug conjugate therapy study. In the present study, monoclonal antibodies (MAbs) against PMEL were obtained by immunizing BALB/c mice with the recombinant PMEL-GST fusion protein. Three mAbs (A3F, G11B, and J7E) with a titer of 1:6000, 1:10,000, and 1:3000, respectively, were obtained. Immunoglobulin subclass assay revealed that A3F was IgG2b, G11B was IgG1, and J7E was IgG2a. Specificity analysis by Western blotting demonstrated that A3F and J7E cross-reacted with GPNMB or LAMP; however, G11B reacted with PMEL only. Immunohistochemistry experiments showed that G11B could bind human PMEL antigen in normal skin. Flow cytometry assay demonstrated that G11B could bind to the surface of PMEL positive melanoma cells but not PMEL negative cells. Taken together, these results show that this G11B provides a useful tool for the antibody drug conjugate therapy study in some pigmentary diseases.

Syndrome Differentiation of Diabetes by the Traditional Chinese Medicine according to Evidence-Based Medicine and Expert Consensus Opinion.

In Chinese medicine, diabetes belongs to the category of "Xiaoke disease (disease with symptoms of frequent drinking and urination)"; in the traditional sense, its pathogenesis is "Yin deficiency and dryness-heat." However, over time, changes in the social environment and lifestyle have also changed the use of traditional Chinese medicine (TCM) in diabetes. In this study, we performed diabetes syndrome differentiation using TCM according to evidence-based medicine and expert consensus opinion.