Flavanomarein inhibits high glucose-stimulated epithelial-mesenchymal transition in HK-2 cells via targeting spleen tyrosine kinase.

Flavanomarein (FM) is a major natural compound of Coreopsis tinctoria Nutt with protective effects against diabetic nephropathy (DN). In this study, we investigated the effects of FM on epithelial-mesenchymal transition (EMT) in high glucose (HG)-stimulated human proximal tubular epithelial cells (HK-2) and the underlying mechanisms, including both direct targets and downstream signal-related proteins. The influence of FM on EMT marker proteins was evaluated via western blot. Potential target proteins of FM were searched using Discovery Studio 2017 R2. Gene Ontology (GO) analysis was conducted to enrich the proteins within the protein-protein interaction (PPI) network for biological processes. Specific binding of FM to target proteins was examined via molecular dynamics and surface plasmon resonance analyses (SPR). FM promoted the proliferation of HK-2 cells stimulated with HG and inhibited EMT through the Syk/TGF-ß1/Smad signaling pathway. Spleen tyrosine kinase (Syk) was predicted to be the most likely directly interacting protein with FM. Combined therapy with a Syk inhibitor and FM presents significant potential as an effective novel therapeutic strategy for DN.

Incidence of and social-demographic and obstetric factors associated with postpartum depression: differences among ethnic Han and Kazak women of Northwestern China.

BACKGROUND: Studies on postpartum depression (PPD) in China have focused primarily on women of Han ethnicity, whereas work on other ethnic groups has proven limited. This study explored the ethnic differences of associated social-demographic and obstetric factors for PPD between Han-majority and Kazak-minority women in northwestern China. METHODS: Han and Kazak women who received routine examinations at four hospitals in a multi-ethnic area of China six weeks after childbirth between March 2016 and December 2016 were included in the study. Data on the women's socio-demographic characteristics, obstetric factors, and possible depression at six weeks after childbirth were collected. We examined the associated factors of PPD using multivariable logistic regression analyses by ethnic group. RESULTS: The overall incidence of PPD was 14.6% (184/1,263) at six weeks after childbirth. PPD was detected more frequently among Kazak (16.1%) than Han women (13.1%). Kazak women exhibited a higher risk of PPD (adjusted OR = 1.561, 95% CI [1.108-2.198], P = 0.011). Urinary incontinence (UI) represented a significant risk factor of PPD for Kazak compared with Han women (OR = 1.720, 95% CI [1.056-2.804], P = 0.003). In contrast, the presence of the mother-in-law as a caregiver after childbirth demonstrated a positive association with PPD among Han (OR = 2.600, 95% CI [1.499-4.512], P = 0.001), but not with Kazak women. CONCLUSIONS: Kazak women were more likely to develop PPD than Han women, even after controlling for confounders. Moreover, distinct risk factors for PPD existed for Han and Kazak women. Future research that explores the relationships between Han women and their mothers-in-law as well as Kazak women's attitudes toward UI could help us further understand PPD in these populations.

Plasma Free Fatty Acids Metabolic Profile Among Uyghurs and Kazaks With or Without Type 2 Diabetes Based on GC-MS.

Free fatty acids (FFAs) participate in a variety of physiological functions. FFAs are associated with the development of type 2 diabetes mellitus (T2DM). Uyghurs and Kazaks have a different prevalence of T2DM, which cannot be explained by traditional risk factors. This study aimed to examine FFAs as potential biomarkers to distinguish between healthy and T2DM Uyghurs and Kazaks. This was a prospective study conducted at the Xianjiang Medical University from 01/2007 to 06/2010 in Uyghurs and Kazaks. The subjects were grouped as T2DM patients (Uyghurs: n=39; Kazaks, n=21) and controls (Uyghurs: n=35; Kazaks, n=40). Gas chromatography-mass spectrometry (GC-MS) and partial least squares discriminant analysis (PLS-DA) models were used to study the FFA profiles between Uyghurs and Kazaks with T2DM. PLS-DA analysis showed that among Kazaks, T2DM patients had lower C22:6, C18:3 n-6, and C20:3 n-6, but higher C22:0 levels compared with controls. Among Uyghurs, the most important variables to discriminate T2DM patients from controls were higher C22:6 and C20:4 n-6, and lower C22:0, C14:1, C18:3 n6, and C20:3 n6. Kazaks and Uyghurs displayed different FFA profiles between patients with T2DM and controls. These results suggest different risk factors and pathogenesis of T2DM between Kazaks and Uyghurs.

[Changes in amino acid profiling in spontaneously hypertensive rats and regulatory effect of extract from Coreopsis tinctoria].

To compare the amino acid metabolic profiling in urine of spontaneously hypertensive rats (SHR) and normal Wistar rats, and investigate the regulatory effect of extract from Coreopsis tinctoria on blood pressure and amino acid metabolic profiling in SHR. Right aged SHR and Wistar rats were housed to fit the new environment for 2 weeks. After that, their systolic pressure(SBP), diastolic pressure(DBP) were measured and urine was collected. Amino acids profiles for SHR and Wistar rats were acquired by using AQC precolumn derivatization HPLC-fluorescence method, and then partial least squares discriminant analysis(PLS-DA) was applied to facilitate differentiation and determine metabolic differences between collected samples from two groups of rats. Consequently, 40 SHR were randomly divided into 5 groups: model group, high, middle, low dosage groups of C. tinctoria extract (3.2, 1.6,0.8 g•kg⁻¹), and captopril group (4 mg•kg⁻¹). They were treated for 4 weeks by ig administration, and then their urine samples were collected to determine the amino acid metabolic profiling in various groups. After treatment for 4 weeks, as compared with Wistar group, serine, alanine, tyrosine, and cystine in the amino acid metabolic profiling were significantly increased in SHR group. As compared with SHR model group, threonine and methionine were decreased significantly in captopril group (P<0.01); amino acid metabolism was changed to different degrees in high, middle, and low dosage groups of C. tinctoria extract, and the threonine in low dose group was significantly decreased (P<0.01); serine and threonine were decreased (P<0.05), and valine, methionine and lysine were significantly decreased (P<0.01) in middle dose group; threonine, valine, methionine and lysine were significantly decreased in large dose group (P<0.01). The results showed that middle and high doses of extract from C. tinctoria could significantly improve disturbance of amino acid metabolism, help to further clarify the drug property research of C. tinctoria, and provide data support for amino acid metabolic pathway abnormalities in hypertension patients.

[Effect of protein intervention on amino acid metabolism spectrum of Qi and Yin deficiency type 2 diabetic rats].

To study the effect of plant protein and animal protein on amino acid metabolism spectrum of Qi and Yin deficiency type 2 diabetic rats. 110 male SD rats were randomly divided into blank group (n=10), diabetic model group (n=20), disease-symptoms group (n=80). The rats of blank group received ordinary feeding, while other groups were fed with high sugar and fat diets. During the whole process of feeding, rats of disease-symptoms group were given with Qingpi-Fuzi (15.75 g•kg⁻¹) once a day through oral administration. Five weeks later, the rats were given with a low dose of STZ (40 mg•kg⁻¹) by intraperitoneal injection to establish experimental diabetic models. Then the models were randomly divided into disease-symptoms group 1 (Qi and Yin deficiency diabetic group, 15.75 g•kg⁻¹), disease-symptoms group 2 (plant protein group, 0.5 g•kg⁻¹), disease-symptoms group 3 (animal protein group, 0.5 g•kg⁻¹), disease-symptoms group 4 (berberine group, 0.1 g•kg⁻¹). The drugs were given for 4 weeks by gavage administration. After 4 weeks of protein intervention, the abdominal aortic blood was collected and serum was isolated to analyze its free amino acid by using AQC pre-column derivatization HPLC and fluorescence detector. Four weeks after the protein intervention, plant protein, animal protein and berberine had no obvious effect on body weight and blood sugar in type 2 diabetic rats. As compared with animal protein group, histidine and proline（P<0.01）, serine, glycine, threonine, alanine, tyrosine, valine, methionine, bright+isoleucine, phenylalanine and lysine（P<0.05）changed a lot in rats serum of plant protein group.The results showed that gavage administration of protein would produce effects on amino acid metabolism of Qi and Yin deficiency type 2 diabetic SD rats. Symbolic differential compounds could be found through metabonomics technology, providing experimental basis for early warning of type 2 diabetes and diagnosis of Qi and Yin deficiency syndrome.

[Progress in preparation of small monoclonal antibodies of knock out technique].

With the application of monoclonal antibody technology more and more widely, its production technology is becoming more and more perfect. Small molecule monoclonal antibody technology is becoming a hot research topic for people. The application of traditional Chinese medicine small molecule monoclonal antibody technology has been more and more widely, the technology for effective Chinese medicine component knockout provide strong technical support. The preparation of monoclonal antibodies and small molecule knockout technology are reviewed in this paper. The preparation of several steps, such as: in the process of preparation of antigen, hapten carrier coupling, coupling ratio determination and identification of artificial antigen and establishment of animal immunization and hybridoma cell lines of monoclonal antibody, the large-scale preparation; small molecule monoclonal antibody on Immune in affinity chromatography column method is discussed in detail. The author believes that this technology will make the traditional Chinese medicine research on a higher level, and improve the level of internationalization of Chinese medicine research.

Expression and activity of the TLR4/NF-κB signaling pathway in mouse intestine following administration of a short-term high-fat diet.

Insulin resistance in obesity is associated with chronic systemic low-grade inflammation. Although it has been shown that Toll-like receptor 4 (TLR4) in the liver, muscle and adipose tissue plays an important role in obesity-associated inflammation and insulin resistance, the effect of TLR4 activation in the intestine has not been investigated. The aim of this study was to explore the activation of the mouse intestinal TLR4/NF-κB signaling pathway following the administration of a short-term high-fat diet, as well as the function of the signaling pathway in the local enteric inflammatory response. The effect of the high-fat diet on TLR4 activation, NF-κB and phosphorylated IκB (PIκB) activity, and tumor necrosis factor (TNF)-α and IL-6 expression in the intestinal tissues of diet-induced obese C57BL/6 mice was investigated. The results demonstrated that the high-fat diet induced TLR4 mRNA and protein expression in intestinal tissues. TLR4/NF-κB signaling pathway activation gradually increased as the number of days of high-fat diet administration increased, and peaked on day 7. Additionally, activation of the signaling pathway reduced PIκB expression levels and increased TNF-α and IL-6 expression levels in intestinal tissues. Our results demonstrated that a short-term high-fat diet induces activation of the TLR4/NF-κB signaling pathway in intestinal tissues, which causes local intestinal low-grade inflammation. These data improve our understanding of the molecular events involved in intestinal low-grade inflammation, which may be the triggering factor for chronic systemic low-grade inflammation.

[Genetic relationships between Tuva population and the neighboring populations in the Altai Region of Xinjiang Uygur Autonomous Region].

In the Hanasi scenic spot of the Altai Region, Xinjiang Uygur Autonomous Region, China, there is a special population known as Xinjiang Tuvinians for short. These Tuvinians were classified as Mongolians in the early 1950s by the National Ethnic Affairs Commission of China, but they claimed that they have an independent origin. To resolve this dispute and their genetic relationships with the people in the neighboring regions, we randomly selected 150 male Tuvinians in the Altai Region. Fourteen Y chromosomal markers were genotyped and eleven haplogroups were constructed. The frequencies of the haplogroups K-M9 and Q-M242 were higher in Xinjiang Tuvinians or Tuvinians in the Tuva Republic than those in the other populations (e.g., Mongolians and Kazakh). Principal component analysis , multi-dimensional scaling analysis and further phylogenetic tree analysis revealed that the Xinjiang Tuvinians were far separated from Mongolians and Kazakh. Based on these results, we proposed that Xinjiang Tuvinians are genetically distinct from Mongolians and Kazakh.

[Synthesis and in vitro antioxidant activity of homo- and heterocyclic diene derivatives of glycyrrhetol].

Chemical modification was performed for improving the antioxidant activity of lead compound glycyrrhetinic acid (Ib). Two conjugated diene derivatives were prepared by reduction and dehydration reactions. Their in vitro antioxidant activities were studied using a cytochrome P450/NADPH reductase system from rat liver microsomes. The generation of microsomal free radicals was followed by oxidation of the DCFH-DA probe, while evaluating the capacity to inhibit reactive oxygen species (ROS) formation. The initial result showed that the two homo- and heterocyclic diene derivatives--18beta-olean-11,13(18)-diene-3beta, 30-diol (IV) and 18beta-olean-9 (11), 12-diene-3beta, 30-diol (V) exhibited strong antioxidant activities, at a concentration of 1.0 mg x mL(-1), they inhibited free radical (ROS) formation by 45% and 41%, respectively. In the same conditions, the lead compound (Ib) and the reference vitamin E inhibited ROS activity by 31% and 32%. Our results suggest that the elimination of the 11-keto group and the chemical reduction of 30-carboxylic group into hydroxyl function can increase the antioxidant activity of Ib significantly.

Analysis of prevalence and risk factors of hypertension among Uygur adults in Tushala and Hetian Xinjiang Uygur autonomous region.

This study was designed to survey the prevalence and risk factors of hypertension in Uygur adults in Tushala Township, Hetian area of Xinjiang Uygur Autonomous Region. Cross-sectional study of possible risk factors for hypertension was conducted in Tushala and in 28 surrounding villages using a stratified random sampling method. A modified version of the WHO STEP wise approach for risk factor survey was employed. Data collection on these relevant risk factors was performed using the WHO STEPS approach. Physical and body parameters were collected and used for analysis of variance. In addition, risk factors for hypertension were screened using a multifactor logistic regression analysis. The prevalence of hypertension in Hetian Township was 25.6%. The incidence of hypertension was positively correlated with body mass index and triglyceride cholesterol. There was also a positive correlation between risk of hypertension and levels of waist-to-hip ratio as well as abdominal circumference (AC). Logistic regression analysis exhibited AC as the predominant risk factor while high-density lipoprotein as the main protective factor for hypertension. In conclusion, our results indicated that high caloric food intake may trigger hyperlipidemia and subsequently elevated blood pressure, with elevated BMI and cholesterol levels being the major risk factors for hypertension.

[A study on the difference between International Diabetes Federation worldwide definition and Adult Treatment Panel III in diagnosing metabolic syndrome].

OBJECTIVE: To study the difference between the metabolic syndrome (MS) diagnosis made with International Diabetes Federation (IDF) worldwide definition and the Adult Treatment Panel III (ATPIII) of National Cholesterol Education Program (NCEP). METHODS: Cross-sectional study and descriptive study were used. RESULTS: There were 1328 MS patients diagnosed with IDF and 1527 MS patients diagnosed with ATPIII. There were 199 MS patients diagnosed with ATPIII but not with IDF and these MS patients all had 3 - 4 risk factors. According to the abnormality of glucose, blood pressure and lipid regulation stated in ATPIII criteria, 759 more patients were diagnosed as MS than with IDF criteria. CONCLUSIONS: MS diagnosed with ATPIII criteria is more objective than with IDF criteria and ATPIII criteria has more space for further theoretical study.

Genetic polymorphism of peroxisome proliferator-activated receptor-gamma 2 Pro12Ala on ethnic susceptibility to diabetes in Uygur, Kazak and Han subjects.

1. The aim of the present study was to determine whether the peroxisome proliferator-activated receptor (PPAR)-g Pro12Ala polymorphism affects susceptibility to diabetes in Uygur, Kazak and Han subjects in Xinjiang, China. 2. Uygur, Kazak and Han subjects from Kashi, Yili and Shawan (Xinjiang, China) were enrolled in the present study. The PPAR-g Pro12Ala polymorphism was determined using restriction fragment length polymorphism. Anthropometric and serum biological indices were monitored among different genotype carriers to examine the PPAR-g Pro12Ala gene polymorphism and the prevalence of type 2 diabetes. 3. The distribution frequency of the Pro12Ala genotype did not differ between diabetic and non-diabetic Uygur, Kazak and Han subjects. However, the frequency of the A allele of Pro12Ala was significant different among non-diabetics, with frequencies of 11, 9 and 5% in Uygur, Kazak and Han groups, respectively. Using the c(2) test, it was shown that the frequency of the A allele in Uygurs (11%) was significantly higher than that in Han subjects (5%). To compare the wild-type (Pro/Pro) carriers in diabetics from each ethnic group, Ugyur subjects, who carry PPAR-g Pro12Ala (Pro/Ala), had a larger waist circumference and lower low-density lipoprotein-cholesterol level, Kazaks subjects showed larger waist circumference and higher high-density lipoprotein levels and Han subjects exhibited a high waist-to-hip ratio and body mass index. 4. The present study revealed that the allele and genotype frequency did not differ in diabetics and non-diabetics of each ethnic group. However, the frequency of the A allele was significantly different in non-diabetics from various ethnic groups. These data suggest that PPAR-g Pro12Ala may affect blood lipid levels and the abdominal fat storage of diabetic Ugyurs and Kazaks and may be associated with fat storage and insulin resistance in Hans.

Associations between 45T/G polymorphism of the adiponectin gene and plasma adiponectin levels with type 2 diabetes.

1. The purpose of the present study was to investigate the association between the single nucleotide polymorphism (SNP) 45T/G and plasma adiponectin levels and the prevalence of Type 2 diabetes mellitus (T2DM) in Uygurs of the Xinjiang region, China. 2. We performed a cross-sectional survey in a representative sample of 151 Uygur adults aged 24-80 years. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to determine the distribution of allele and genotype frequency of the SNP45 T/G polymorphism (exon 2) in the adiponectin gene. An ELISA was used to determine plasma adiponectin levels. Logistic regression was used to screen risk factors for T2DM. 3. Compared with the normal glucose tolerance (NGT) group, the T2DM group exhibited a higher distribution of the TG + GG genotype, G allele frequency and lower plasma adiponectin concentrations in TG + GG genotype carriers compared with those with the TT genotype. Compared with SNP45 T carriers, in the NGT group, G carriers had higher levels of systolic and diastolic blood pressure, low density lipoprotein (P < 0.05) and total cholesterol (P < 0.005). In the T2DM group, G carriers had lower levels of homeostasis model assessment (HOMA) of insulin sensitivity (P < 0.05) and higher levels of HOMA of insulin resistance (P < 0.05). 4. Adiponectin SNP 45 is positively correlated with the prevalence of T2DM in Uygurs of Xinjiang. The G allele carriers who have reduced plasma concentrations of adiponectin may have associated insulin resistance.