[Comparison of coagulation function between adrenocorticotropic hormone independent Cushing syndrome and nonfunctional adrenal adenoma and its influence factors].

OBJECTIVE: To investigate the coagulation function indicators and identify influence factors of hypercoagulability in patients with adrenocorticotropic hormone (ACTH) independent Cushing syndrome (CS). METHODS: In our retrospective study, the electronic medical records system of Peking University First Hospital was searched for the patients diagnosed with ACTH independent CS on discharge from January 2014 to June 2019. Nonfunctional adrenal adenoma patients were chosen as control group and matched 1 ∶1 by body mass index (BMI), gender, and discharge date. Clinical features and coagulation function indicators were compared between the two groups. RESULTS: In the study, 171 patients were included in each group. Compared with control group, activated partial thromboplastin time (APTT), and prothrombin time (PT) in ACTH independent CS group were significantly lower [(29.22±3.39) s vs. (31.86±3.63) s, P < 0.001; (29.22±3.39) s vs. (31.86±3.63) s, P < 0.001], and both D-dimer and fibrin degradation products (FDP) levels were significantly higher (P < 0.05). Percentage of APTT levels under the lower limit of reference range in the CS patients was significantly higher than that in nonfunctional group (21.6% vs. 3.5%, P < 0.001). Percentage of D-dimer levels over the upper limit of reference range in the CS patients was significantly higher than that in nonfunctional group (13.5% vs. 6.6%, P=0.041). There were three patients with deep venous thrombosis and one patient with pulmonary embolism in CS group, however none was in control group. The area under curve (AUC) of serum cortisol rhythm (8:00, 16:00 and 24:00) levels was negatively associated with the levels of PT (r=-0.315, P < 0.001) and APTT (r=-0.410, P < 0.001), and positively associated with FDP (r=0.303, P < 0.001) and D-dimer levels (r=0.258, P < 0.001). There were no differences in coagulation function indicators among different histopathologic subgroups (adrenocortical adenoma, adrenocortical hyperplasia, oncocytic adenoma, adrenocortical carcinoma). With Logistic regression analysis, the AUC of cortisol and glycosylated hemoglobin A1c (HbA1c) levels were independent risk factors for hypercoagulability in the ACTH independent CS patients (P < 0.05). CONCLUSION: ACTH independent CS patients were more likely in hypercoagulable state compared with nonfunctional adrenal adenoma, especially in ACTH independent CS patients with higher levels of cortisol AUC and HbA1c. These patients should be paid attention to for the hypercoagulability and thrombosis risk.

Delayed diagnosis of acromegaly in a patient with focal segmental Glomerulosclerosis: a rare case report and literature review.

BACKGROUND: Experimental studies have demonstrated that hypersecretion of growth hormone (GH) is associated with development of glomerular sclerosis. However, clinical case of such condition is very rare. Here we presented a case of focal segmental glomerulosclerosis (FSGS) associated with acromegaly. CASE PRESENTATION: A 63-year-old man was diagnosed as nephrotic syndrome with minimal change disease for 2 years. Prednisone 1 mg/kg/day for 9 months led to no response. After admission, the second kidney biopsy indicated FSGS (NOS variant). On admission, his acromegalic features were noticed and he complained with a 20-year history of soft tissue swelling of hands and feet. Serum GH and insulin-like growth factor 1 (IGF-1) concentrations were both elevated significantly. An oral glucose tolerance test showed inadequate suppression of serum GH. The presence of a pituitary macroadenoma with a diameter of 1.4 cm by MRI confirmed the diagnosis of acromegaly. Then, the tumor was subtotally removed by trans-sphenoidal surgery. Partial remission of proteinuria was achieved 3 months after surgery and maintained during follow-up, with gradual reduce of corticosteroid. CONCLUSIONS: This rare case suggested that the hypersecretion of GH may participate, at least in part, in FSGS development and progression. Early diagnosis and treatment of acromegaly is beneficial.

Effects of diurnal temperature range on mortality in Hefei city, China.

Although several studies indicated an association between diurnal temperature range (DTR) and mortality, the results about modifiers are inconsistent, and few studies were conducted in developing inland country. This study aims to evaluate the effects of DTR on cause-specific mortality and whether season, gender, or age might modify any association in Hefei city, China, during 2007-2016. Quasi-Poisson generalized linear regression models combined with a distributed lag non-linear model (DLNM) were applied to evaluate the relationships between DTR and non-accidental, cardiovascular, and respiratory mortality. We observed a J-shaped relationship between DTR and cause-specific mortality. With a DTR of 8.3 °C as the reference, the cumulative effects of extremely high DTR were significantly higher for all types of mortality than effects of lower or moderate DTR in full year. When stratified by season, extremely high DTR in spring had a greater impact on all cause-specific mortality than other three seasons. Male and the elderly (≥ 65 years) were consistently more susceptible to extremely high DTR effect than female and the youth (< 65 years) for non-accidental and cardiovascular mortality. To the contrary, female and the youth were more susceptible to extremely high DTR effect than male and the elderly for respiratory morality. The study suggests that extremely high DTR is a potential trigger for non-accidental mortality in Hefei city, China. Our findings also highlight the importance of protecting susceptible groups from extremely high DTR especially in the spring.

The relationship between demands for lung cancer screening and the constructs of health belief model: a cross-sectional survey in Hefei, China.

The aim of investigation is to explore the relationship between demands for lung cancer screening (LCS) and the constructs derived from the health belief model (HBM) in Hefei. The study collected data about socio-demographics, health beliefs in and demands for LCS during early June to later July 2015. By constructing a LCS demands HBM constructs, it calculated indices of demands for LCS (DSI) and HBM constructs, which include perceived risk (PR) and seriousness (PS) of the cancers; and perceived effectiveness (PE), benefits (PB) and difficulties (PD) of the screening. It also performed descriptive and multivariate regression analysis of the demands and the HBM constructs. The amount of 823 respondents participated and completed the survey. 6.4% of them had ever undertaken LCS, whereas 60.1% of them expressed willingness to accept the service of LCS if it is free. In multiple regression analysis which used weights in calculating the HBM construct indices, education displayed significant positive associations with DSI (p = .044), and most of HBM constructs indices (PSI, PRI, PBI, and PDI) were statistically significant with DSI (p < .05). HBM-based constructs regarding LCS have important effects on demands for the service, and may provide effective paths to cancer screening promotion.

Impact of meteorological changes on the incidence of scarlet fever in Hefei City, China.

Studies on scarlet fever with meteorological factors included were few. We aimed to illustrate meteorological factors' effects on monthly incidence of scarlet fever. Cases of scarlet fever were collected from the report of legal infectious disease in Hefei City from 1985 to 2006; the meteorological data were obtained from the weather bureau of Hefei City. Monthly incidence and corresponding meteorological data in these 22 years were used to develop the model. The model of auto regressive integrated moving average with covariates was used in statistical analyses. There was a highest peak from March to June and a small peak from November to January. The incidence of scarlet fever ranges from 0 to 0.71502 (per 105 population). SARIMAX (1,0,0)(1,0,0)12 model was fitted with monthly incidence and meteorological data optimally. It was shown that relative humidity (ß = -0.002, p = 0.020), mean temperature (ß = 0.006, p = 0.004), and 1 month lag minimum temperature (ß = -0.007, p < 0.001) had effect on the incidence of scarlet fever in Hefei. Besides, the incidence in a previous month (AR(ß) = 0.469, p < 0.001) and in 12 months before (SAR(ß) = 0.255, p < 0.001) was positively associated with the incidence. This study shows that scarlet fever incidence was negatively associated with monthly minimum temperature and relative humidity while was positively associated with mean temperature in Hefei City, China. Besides, the ARIMA model could be useful not only for prediction but also for the analysis of multiple correlations.

Different accumulation profiles of multiple components between pericarp and seed of Alpinia oxyphylla capsular fruit as determined by UFLC-MS/MS.

Plant secondary metabolites are known to not only play a key role in the adaptation of plants to their environment, but also represent an important source of active pharmaceuticals. Alpinia oxyphylla capsular fruits, made up of seeds and pericarps, are commonly used in traditional East Asian medicines. In clinical utilization of these capsular fruits, inconsistent processing approaches (i.e., hulling pericarps or not) are employed, with the potential of leading to differential pharmacological effects. Therefore, an important question arises whether the content levels of pharmacologically active chemicals between the seeds and pericarps of A. oxyphylla are comparable. Nine secondary metabolites present in A. oxyphylla capsular fruits, including flavonoids (e.g., tectochrysin, izalpinin, chrysin, apigenin-4',7-dimethylether and kaempferide), diarylheptanoids (e.g., yakuchinone A and B and oxyphyllacinol) and sesquiterpenes (e.g., nootkatone), were regarded as representative constituents with putative pharmacological activities. This work aimed to investigate the abundance of the nine constituents in the seeds and pericarps of A. oxyphylla. Thirteen batches of A. oxyphylla capsular fruits were gathered from different production regions. Accordingly, an ultra-fast high performance liquid chromatography/quadrupole tandem mass spectrometry (UFLC-MS/MS) method was developed and validated. We found that: (1) the nine secondary metabolites were differentially concentrated in seeds and fruit capsules; (2) nootkatone is predominantly distributed in the seeds; in contrast, the flavonoids and diarylheptanoids are mainly deposited in the capsules; and (3) the content levels of the nine secondary metabolites occurring in the capsules varied greatly among different production regions, although the nootkatone levels in the seeds were comparable among production regions. These results are helpful to evaluating and elucidating pharmacological activities of A. oxyphylla capsular fruits. Additionally, it may be of interest to elucidate the mechanisms involved in the distinct accumulation profiles of these secondary metabolites between seeds and pericarps.

Micronutrients, their potential effect on patients with systemic sclerosis.

Over the past years, several evidences have supported an important role of specific micronutrients, including vitamin A, vitamin D and vitamin E in immune dysfunction, vascular involvement and fibrotic changes involved in systemic sclerosis (SSc) development. In PubMed, eight clinical trials about the therapy of micronutrients on SSc patients were searched out using medical subject headings terms (SSc: "scleroderma, localized", "scleroderma, systemic", "scleroderma, diffuse" and "scleroderma, limited"; vitamins "vitamin A", "thiamin", "riboflavin", "niacin", "pantothenic acid", "vitamin B 6", "biotin", "folic acid", "vitamin B 12", "inositol", "choline", "ascorbic acid", "vitamin D", "vitamin E", "tocopherols", "vitamin K" and "vitamin P"; and minerals: "calcium", "magnesium", "potassium", "sodium", "phosphorus", "sulfur", "chlorine", "iron", "copper", "iodine", "zinc", "selenium", "manganese", "molybdenum", "cobalt", "chromium", "tin", "vanadium", "silicon", "nickel" and "fluorine"). This brief review will summarize current understanding on that for the further prospect of future studies. Though the clinical trials for the treatment of SSc with micronutrients are still in their infancy, more researches are needed to substantiate the current results and accelerate the knowledge in this field.

Regulation of human pregnane X receptor and its target gene cytochrome P450 3A by praeruptorin A isolated from the herbal medicine Peucedanum praeruptorum.

Qianhu, the dried roots of Peucedanum praeruptorum, is a well-known traditional Chinese medicinal herb which was officially listed in the Chinese Pharmacopoeia. Praeruptorin A is the major active constituent of Qianhu. Our previous studies show that praeruptorin effectively transactivated the protein expression and catalytic activity of cytochrome P450 3A4 via the constitutive androstane receptor-mediated pathway. However, the effect of praeruptorin on the transactivation of cytochrome P450 3A4 through pregnane X receptor pathway is still unclear. To further elucidate the role of the pregnane X receptor pathway in the up-regulation of cytochrome P450 3A4 by praeruptorin, in this study, the effect of praeruptorin on the cytochrome P450 3A4 gene expression was investigated in mouse primary hepatocytes after knockdown of the pregnane X receptor by transient transfection of its siRNA; and the gene expression, protein expression, and catalytic activity of cytochrome P450 3A4 in the LS174T cells with pregnane X receptor overexpression were determined by real-time PCR, Western blot analysis, and LC-MS/MS-based cytochrome P450 3A4 substrate assay, respectively. We found that the level of cytochrome P450 3a11 gene expression in mouse primary hepatocytes was significantly increased by praeruptorin, but such an induction was suppressed after knockdown of pregnane X receptor by its siRNA. Praeruptorin significantly induced cytochrome P450 3A4 mRNA, protein expression, and functional activity through pregnane X receptor-mediated pathway in pregnane X receptor-overexpression LS174T cells; conversely, induction was not found in LS174T cells untransfected with pregnane X receptor plasmids. These findings suggest that praeruptorin can significantly up-regulate cytochrome P450 3A4 gene via the pregnane X receptor-mediated pathway, and this should be taken into consideration in potential herb-drug interactions.

[Efficacy judgment for treating ischemic stroke by acupuncturing at Neiguan (PC6) and the screening for optimal parameters].

OBJECTIVE: To select optimal parameters and judge the comprehensive effect of acupuncture. METHODS: The middle cerebral artery occlusion (MCAO) rat model was duplicated. Nine acupuncture parameters groups were set up by the frequency of acupuncture (slow, medium, and fast: 60, 120, and 180 times/min) and the acupuncture duration (short, medium, and long: 5, 60, and 180 s). Twisting technique was used in needling at Neiguan (PC6). By taking neurological impairment scoring, leptomeningeal cerebral blood flow, microcirculation (input branch diameter, output branch diameter, input/output), and cerebral infarction rate as effect indicators, the comprehensive effects of different acupuncture parameters at Neiguan (PC6) on MCAO were determined by factor analysis, thus screening the optimal parameters. RESULTS: By factor analysis, the highest score for comprehensive effect could be achieved with the acupuncture parameters of 180 times/min and 60 s. That is to say, fast frequency and middle time duration could achieve the optimal acupuncture effects, suggesting that appropriate acupuncture time duration should be used under the condition of guaranteeing fast frequency when treating ischemic stroke by needling at Neiguan (PC6). CONCLUSION: The 180 times/min and 60 s were the optimal parameter group when needling at Neiguan (PC6) by twisting technique for treating ischemic stroke.

Cellular senescence of renal tubular epithelial cells in renal fibrosis.

Renal fibrosis (RF) is the common pathological manifestation of virtually all chronic kidney diseases (CKD) and one of the major causes of end-stage renal disease (ESRD), but the pathogenesis of which is still unclear. Renal tubulointerstitial lesions have been identified as a key pathological hallmark of RF pathology. Renal tubular epithelial cells are the resident cells of the tubulointerstitium and play an important role in kidney recovery versus renal fibrosis following injury. Studies in recent years have shown that senescence of renal tubular epithelial cells can accelerate the progression of renal fibrosis. Oxidative stress(OS), telomere attrition and DNA damage are the major causes of renal tubular epithelial cell senescence. Current interventions and therapeutic strategies for cellular senescence include calorie restriction and routine exercise, Klotho, senolytics, senostatics, and other related drugs. This paper provides an overview of the mechanisms and the key signaling pathways including Wnt/ß-catenin/RAS, Nrf2/ARE and STAT-3/NF-κB pathway involved in renal tubular epithelial cell senescence in RF and therapies targeting renal tubular epithelial cell senescence future therapeutic potential for RF patients. These findings may offer promise for the further treatment of RF and CKD.

Prevalence of unprotected anal intercourse and unprotected vaginal intercourse among HIV-positive men who have sex with men in China: a meta-analysis.

This study aims at deriving a general description of the prevalence of unprotected anal intercourse among HIV-positive MSM in China using published epidemiological research. Comprehensively searching Wanfang, Weipu, China Biological Medicine (CBM), Chinese National Knowledge Infrastructure (CNKI) and Pubmed databases in the systematic review. Meta-analysis were conducted over a final set of nineteen studies (n=1603). The pooled prevalence of unprotected anal intercourse among HIV-positive MSM was 75.4% (95% CI: 67.5%∼82.5%) and unprotected vaginal intercourse was 68.0% (95% CI: 46.0%∼86.4%). The prevalence of unprotected anal intercourse differed significantly in sampling method, data collection method, sample size, location, recruitment setting and data collection period. Studies with the following features had a higher prevalence of unprotected anal intercourse: recruiting participants from 2005 to 2007, sample size being below 50, recruiting participants from MSM venues/internet, using convenience sampling, study location being Chongqing city, and using interviewer administered questionnaire. Findings from this meta-analysis indicate that a majority percentage of HIV-positive MSM engage in unprotected sexual behavior. So that place their sex partners at risk for infecting HIV and also place themselves at risk for other sexually transmitted diseases. An effective strategy for prevention and control is required for this specific population in China.

Association of the interleukin-10 1082G/A, 819C/T and 3575T/A gene polymorphisms with systemic sclerosis: a meta-analysis.

Many environmental and genetic factors have been contributed to the development of systemic sclerosis (SSc). To determine whether IL-10 gene polymorphisms are associated with SSc, we conducted a meta-analysis approach. A total of eight studies involving 1,034 SSc cases and 1,815 controls were obtained by electronic database, i.e. Embase, Blackwell, Scopus, China National Knowledge Infrastructure database, Chinese Biomedical database, Google searching. We analyzed three gene polymorphisms, including IL-10 -1082G/A (rs1800896), IL-10 -819C/T (rs1800871), IL-10 -3575T/A (rs1800890). The combined odds ratio (OR) with its 95% confidence interval (95% CI) was calculated using fixed or random effect models. We found that IL-10 819C allele might contribute to SSc susceptibility by fixed effect model and IL-10 3575A allele could be an important risk factor for SSc, especially in European descent. No significant heterogeneity were observed. Under random effect model, there was no evidence of statistically significant association between IL-10 1082G/A polymorphism and SSc. Publication bias was absent in all analyses. However, larger scale primary studies are required to further evaluate the IL-10 polymorphism and SSc.

Three-target treatment combined with surgery for BRAF V600E-mutant colon cancer with peritoneal metastasis: a case report.

Background: BRAF V600E-mutant advanced colon cancer with peritoneal metastasis is associated with a poor prognosis. Surgery is not recommended by current guidelines, and there are few cases demonstrating the efficacy of targeted therapy combined with surgery in such patients. In the era of precision medicine, we apply aggressive surgery after successful conversion of triple-targeted drugs to prolong survival and provide a clinical basis for the treatment of such patients. Case Description: A 72-year-old male patient presented with abdominal distension and changes in bowel habits was admitted to the Department of Oncology, Shanxi Provincial People's Hospital. The patient was diagnosed with advanced ascending colon adenocarcinoma with peritoneal metastasis after relevant examinations such as abdominal enhanced computed tomography and tests of tumor markers. Later, further genetic testing was performed suggesting BRAF V600E mutation. We treated the patient with first-line three-target therapy (dabrafenib + trametinib + cetuximab). Repeat abdominal enhanced computed tomography after 6 weeks of three-target therapy revealed the disappearance of peritoneal metastases. Subsequently, after 3 months, the patient underwent resection of the primary lesion and removal of greater omental metastases. Three-target therapy continued after surgery until 4 months post-operation. However, carbohydrate antigen 199 was significantly increased at 9 months after medication discontinuation, and returned to normal after 4 months of re-initiation of three-target therapy. The three-target therapy was further adjusted to two-target therapy (dabrafenib + cetuximab) based on the results of circulating tumor cells, and the tumor markers are now normal. Conclusions: Patients with BRAF V600E colon cancer combined with peritoneal metastases are treated with targeted drug conversion therapy, and aggressive surgery may prolong survival depending on the conversion effect. Continued maintenance therapy after surgery may play a role in preventing recurrence.

Heidihuangwan alleviates renal fibrosis in rats with 5/6 nephrectomy by inhibiting autophagy.

Renal fibrosis is a common pathway for the progression of various chronic kidney diseases (CKD), and the formation and deterioration will eventually lead to end-stage renal failure, which brings a heavy medical burden to the world. HeidihuangWan (HDHW) is a herbal formulation with stable and reliable clinical efficacy in the treatment of renal fibrosis. However, the mechanism of HDHW in treating renal fibrosis is not clear. In this study, we aimed to investigate the mechanism of HDHW to improve renal fibrosis. Wistar rats were randomly divided into the normal control group, 5/6 Nephrectomy group, astragaloside IV (AS-IV) group, HDHW group, and HDHW + IGF-1R inhibitor (JB1) group. Except for the normal control group, the rat renal fibrosis model was established by 5/6 nephrectomy and intervened with drugs for 8 weeks. Blood samples were collected to evaluate renal function. Hematoxylin-Eosin (HE), Periodic Acid-Schiff (PAS), Modified Masson's Trichrome (Masson) staining were used to evaluate the pathological renal injury, and immunohistochemistry and Western blotting were used to detect the protein expression of renal tissue. The results showed that HDHW was effective in improving renal function and reducing renal pathological damage. HDHW down-regulated the levels of fibrosis marker proteins, including α-smooth muscle actin (α-SMA), vimentin, and transforming growth factors-ß(TGF-ß), which in turn reduced renal fibrosis. Further studies showed that HDHW down-regulated the expression of autophagy-related proteins Beclin1 and LC3II, indicating that HDHW inhibited autophagy. In addition, we examined the activity of the class I phosphatidylinositol-3 kinase (PI3K)/serine-threonine kinase (Akt)/mTOR pathway, an important signaling pathway regulating autophagy, and the level of insulin-like growth factor 1 (IGF-1), an upstream activator of PI3K/Akt/mTOR. HDHW upregulated the expression of IGF-1 and activated the PI3K/Akt/mTOR pathway, which may be a vital pathway for its inhibition of autophagy. Application of insulin-like growth factor 1 receptor (IGF-1R) inhibitor further confirmed that the regulation of autophagy and renal fibrosis by HDHW was associated with IGF-1-mediated activation of the PI3K/Akt/mTOR pathway. In conclusion, our study showed that HDHW inhibited autophagy by upregulating IGF-1 expression, promoting the binding of IGF-1 to IGF-1R, and activating the PI3K/Akt/mTOR signaling pathway, thereby reducing renal fibrosis and protecting renal function. This study provides support for the application and further study of HDHW.

A diarylheptanoid compound from Alpinia officinarum Hance ameliorates high glucose-induced insulin resistance by regulating PI3K/AKT-Nrf2-GSK3ß signaling pathways in HepG2 cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Alpinia officinarum Hance, a perennial natural medicine-food herb, has been traditionally used to treat colds, stomachache, and diabetes for thousands of years. 1,7-Diphenyl-4E-en-3-heptanone (DPH5), a diarylheptanoid isolated from the rhizome of A. officinarum has been reported to be safe and to have antioxidant and hypoglycemic effects, suggesting its potential in the treatment of insulin resistance (IR). AIM OF THE STUDY: Aim of to investigate the protective effect of DPH5 on IR and elucidate its underlying mechanism of action. MATERIALS AND METHODS: HepG2 cells were used as the research objects. Glucose uptake and reactive oxygen species (ROS) levels in high glucose-induced insulin-resistant HepG2 cells were assessed using flow cytometry. Glucose consumption and the levels of malondialdehyde (MDA) and superoxide dismutase (SOD) were analyzed using the corresponding assay kits. The expression of mRNA and proteins related to insulin signaling, glucose metabolism, and antioxidant factor, including insulin receptor substrate-1 (IRS1), phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), translocation of glucose transporter-4, glycogen synthase kinase-3ß (GSK3ß), glucokinase (GCK), pyruvate kinase (PK), phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphatase (G6Pase), nuclear factor-erythroid 2 related factor 2 (Nrf2), heme oxygenase-1 (HO-1), NADPH quinoneoxidoreductase (NQO1), and glutathione peroxidase (GSH-Px) was determined using real-time quantitative polymerase chain reaction and western blotting. Furthermore, molecular docking was performed to determine the spatial mechanism of DPH5 on the key targets PI3K, AKT, Nrf2, and GSK3ß. RESULTS: DPH5 could improve IR that manifested as increased glucose uptake and glucose consumption in insulin-resistant HepG2 cells. Moreover, DPH5 could enhance antioxidant capacity by activating Nrf2/HO-1 elements, including increasing Nrf2, HO-1, SOD, NQO1, and GSH-Px expression and reducing MDA, ROS, and JNK levels, thereby improving oxidative stress and ultimately alleviating IR. Additionally, DPH5 could promote the expression of IRS1, PI3K, AKT, GSK3ß, GCK, and PK, and downregulate the expression of PEPCK and G6pase, thereby accelerating glucose utilization and enhancing insulin sensitivity. The mechanism underlying the effect of DPH5 in alleviating IR was related to the PI3K/AKT- and Nrf2/HO-1-mediated regulation of the GSK3ß signaling pathway, and the results were further confirmed using the specific inhibitors LY294002 and ML385. Results from molecular docking indicated that there were different regulatory sites and interacting forces between DPH5 and PI3K, AKT, Nrf2, and GSK3ß; however, the binding force was relatively strong. CONCLUSIONS: DPH5 improved oxidative stress and glucose metabolism via modulating the PI3K/AKT-Nrf2-GSK3ß pathway, thereby ameliorating IR. Overall, our findings suggest the potential of DPH5 as a natural medicine to treat type-2 diabetes mellitus.

Association of p53 codon 72 polymorphism with prostate cancer: a meta-analysis.

Relationship of prostate cancer with the polymorphism of p53 codon 72 was reported with inconsistent results. The purpose of this study was to quantitatively evaluate the association between p53 codon 72 polymorphism and prostate cancer susceptibility. We performed an extensive search of relevant studies and made a meta-analysis, including 8 studies with 815 prostate cancer cases and 1047 controls. The combined results showed that there were no significant differences in genotype distribution between prostate cancer cases and control on the basis of all studies, CC/GC versus GG (OR = 1.24, 95% CI: 0.93-1.65), GG/GC versus CC (OR = 0.96, 95% CI: 0.60-1.55), GC versus GG (OR = 1.27, 95% CI: 0.91-1.77), CC versus GG (OR = 1.25, 95% CI:0.74-2.12), GC versus CC (OR = 1.09, 95% CI: 0.63-1.87). When stratifying for the race, there were also no statistically significant differences in genotype distribution between prostate cancer cases and controls. This meta-analysis did not provide an evidence of confirming association between p53 codon 72 polymorphism and prostate cancer.

A new indole alkaloid with HUVEC proliferation activities from Nauclea officinalis.

A new indole alkaloid, namely naucleofficine H (1), was obtained from the aqueous extract of Nauclea officinalis, together with four known alkaloids, vincosamide (2), strictosamide (3), angustoline (4) and pumiloside (5). Their structures were characterized by analyzing their physicochemical data including NMR, and HRMS. In addition, five compounds were tested for their proliferation activities. The expression of vascular endothelial growth factor (VEGF), extra-cellular signal-regulated protein kinase 1 and 2 (ERK) and phosphorylation of ERK 1/2 (p-ERK) were also detected in HUVEC treated withbioactive compounds using western blotting. The result showed that these compounds could promote HUVEC cell proliferation. Compounds 3 and 5 could up-regulate VEGF and p-ERK in HUVEC.

Morus alba L. Leaves - Integration of Their Transcriptome and Metabolomics Dataset: Investigating Potential Genes Involved in Flavonoid Biosynthesis at Different Harvest Times.

The mulberry leaf is a classic herb commonly used in traditional Chinese medicine. It has also been used as animal feed for livestock and its fruits have been made into a variety of food products. Traditionally, mulberry (Morus alba L.) leaf harvesting after frost is thought to have better medicinal properties, but the underlying mechanism remains largely unsolved. To elucidate the biological basis of mulberry leaves after frost, we first explored the content changes of various compounds in mulberry leaves at different harvest times. Significant enrichment of flavonoids was observed with a total of 224 differential metabolites after frost. Subsequently, we analyzed the transcriptomic data of mulberry leaves collected at different harvest times and successfully annotated 22,939 unigenes containing 1,695 new genes. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed 26, 20, and 59 unigenes related to flavonoids synthesis in three different groups harvested at different times. We found that the expression levels of flavonoid biosynthesis-related unigenes also increased when harvested at a delayed time, which was consistent with the flavonoid accumulation discovered by the metabolomic analysis. The results indicated that low temperature may be a key trigger in flavonoid biosynthesis of mulberry leaves by increasing the expression of flavonoid biosynthesis-related genes. This study also provided a theoretical basis for the optimal harvest time of mulberry leaves.

Two new drimane sesquiterpenoids from compound Changweikang and their inhibitory activity against nitric oxide production.

Two new drimane sesquiterpenoids, changweikangic acid A (1) and B (2), were isolated from Compound Changweikang. Their structures were established on basis of extensive spectroscopic analyses including two dimensional (2D) NMR and X-ray crystallographic data. The two compounds were evaluated for their inhibitory activity against nitric oxide production in lipopolysaccharide-activated macrophage cell line, RAW 264.7 cells.

[Alkaloids from the leaves of Nauclea officinalis].

To study chemical constituents of the leaves of Nauclea officinalis, eight alkaloids were isolated from 95% ethanol extract by various chromatographic methods. The structures were elucidated on the basis of spectroscopic data (IR, UV, ESI-MS, 1D and 2D NMR) and identified as naucleactonin C (1), strictosamide (2), vincosamide (3), pumiloside (4), angustoline (5), angustine (6), 18, 19-dihydroangustine (7) and naucleofficine D (8). Compound 1 is a new indole alkaloid. Compounds 6 and 7 were isolated from this plant for the first time.