[Different processed products of Polygonati Rhizoma treat Alzheimer's disease in rats: urine metabolomics based on UPLC-Q/TOF-MS].

The study investigated the effects of different processed products of Polygonati Rhizoma(black bean-processed Polygonati Rhizoma, BBPR; stewed Polygonati Rhizoma, SPR) on the urinary metabolites in a rat model of Alzheimer's disease(AD). Sixty SPF-grade male SD rats were randomized into a control group, a model group, a donepezil group, a BBPR group, and a SPR group, with twelve rats in each group. Other groups except the control group were administrated with D-galactose injection(100 mg·kg~(-1)) once a day for seven weeks. The control group was administrated with an equal volume of normal saline once a day for seven consecutive weeks. After three weeks of D-galactose injection, bilateral hippocampal Aß_(25-35) injections were performed for modeling. The rats were administrated with corresponding drugs(10 mL·kg~(-1)) by gavage since week 2, and the rats in the model and control group with an equal volume of double distilled water once a day for 35 continuous days. The memory behaviour and pathological changes in the hippocampal tissue were observed. The untargeted metabolites in the urine were detected by ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry(UPLC-Q/TOF-MS). Principal component analysis(PCA) and orthogonal partial least square-discriminant analysis(OPLS-DA) were employed to characterize and screen differential metabolites and potential biomarkers, for which the metabolic pathway enrichment analysis was conducted. The results indicated that BBPR and SPR increased the new object recognition index, shortened the escape latency, and increased the times of crossing the platform of AD rats in the Morris water maze test. The results of hematoxylin-eosin(HE) staining showed that the cells in the hippocampal tissue of the drug administration groups were closely arranged. Moreover, the drugs reduced the content of interleukin-6(IL-6, P<0.01) and tumor necrosis factor-α(TNF-α) in the hippocampal tissue, which were more obvious in the BBPR group(P<0.05). After screening, 15 potential biomarkers were identified, involving two metabolic pathways: dicoumarol pathway and piroxicam pathway. BBPR and SPR may alleviate AD by regulating the metabolism of dicoumarol and piroxicam.

Medical students' preclinical service-learning experience and its effects on empathy in clinical training.

BACKGROUND: Service learning (SL) is an educational methodology presumed to help medical students be more empathetic and compassionate. We longitudinally investigated the level of empathy in medical students and how preclinical SL experience was related to their level of empathy in their clinical clerkships. METHODS: Our cohort comprised fifth-year medical students engaged in clerkships as part of a 7-year medical programme at one medical school in Taiwan. Surveys were conducted at the beginning of the clerkship in September 2015 (T1) to collect data on the medical students' preclinical SL experience in curriculum-based service teams (CBSTs) and extracurricular service teams (ECSTs) and their SL self-efficacy, demographic characteristics, and empathy level. Subsequently, three follow-up surveys were conducted once every 3 months to determine the empathy level of the students during their clinical clerkships (T2-T4). Seventy students who returned the written informed consent and completed the baseline (T1) and two or more follow-up surveys (T2-T4) were included in our analysis with the response rate of 34%. In total, 247 responses across the 1-year clerkship were analysed. Descriptive statistics, paired t tests, and generalised estimating equations were employed. RESULTS: Our study revealed that changes in empathy level in the dimensions of perspective taking, compassionate care, and standing in patients' shoes in their clinical clerkships. Relative to that at T1, their empathy decreased in perspective taking and compassionate care at T2-T4 but increased in standing in patients' shoes at T3. Additionally, our study verified the positive effect of medical students' preclinical SL experience in CBSTs and ECSTs on empathy in terms of compassionate care and perspective taking, respectively, but not on that of standing in patients' shoes. CONCLUSIONS: Separate investigations into subconstructs of empathy, such as perspective taking, compassionate care, and standing in patients' shoes, in medical students may be necessary for exploring the various driving forces or barriers to developing empathy in medical students. Moreover, SL experience through both CBSTs and ECSTs at medical academies may have positive effects on medical students' empathy in their clinical clerkships and should be promoted at medical schools.

[Chemical Constituents from Stauntonia chinensis].

Objective: To study the chemical constituents of Stauntonia chinensis. Methods: The chemical constituents were isolated and purified by column chromatography on silica gel,ODS,Sephadex LH-20 and MPLC. Their structures were elucidated on the basis of physicochemical properties and special analysis. Results: Seven compounds were isolated from the leaves of Stauntonia chinensis,whose structures were elucidated as 3-O-ß-D-glucopyranosyl-( 1 →3)-[ß-D-xylopyranosyl-( 1 →2) ]-α-L-arabinopyranosyl-28-O-[α-L-rhamnopyranosyl-( 1 →4)-ß-D-glucopyranosyl-( 1 →6)-ß-D-glucopyranosyl]-3ß-hydroxy-30-norolean-12,20( 29)-dien-28-oic acid( 1),3-[( O-ß-D-glucopyranosyl-( 1→3)-[α-L-rhamnopyranosyl-( 1 →2) ]-α-L-arabinopyranosyl) oxy]-30-norolean-12,20( 29)-dien-28-oic acid O-ß-D-glucopyranosyl-( 1 → 6)-ß-D-glucopyranosyl ester( 2),3-O-ß-D-[( α-L-xylopyranosyl-( 1 → 2)-O-α-L-arabinopyranosyl)oxy]-30-norolean-12-en-28-oic acid α-L-rhamnopyranosyl-( 1 → 4)-O-ß-D-glucopyranosyl-( 1 → 6)-O-ß-D-glucopyranosyl ester( 3), yemuoside YM27( 4), yemuoside YM21( 5),yemuoside YM10( 6) and yemuoside YM7( 7). Conclusion: Compounds 1 ~ 3 are isolated from this plant for the first time.

Triterpenoid glycosides from Stauntonia chinensis.

A new bidesmoside triterpenoid saponin, named stauntoside C1 (1), along with three known saponins (2-4) was isolated from Stauntonia chinensis DC. (Lardizabalaceae). Their structures were established by means of spectral and chemical methods as 3-O-beta-D-xylopyranosyl-(1 --> 2)-O-beta-D-xylopyranosyl-(1 --> 3)-O-alpha-L-rhamnopyranosyl-(1 --> 2)-alpha-L-arabinopyranosyl oleanolic acid 28-O-alpha-L-rhamnopyranosyl-(1 --> 4)-beta-D-glucopyranosyl-(1 --> 6)-beta-D-glucopyranosyl ester (1), scabiosaponin E (2), sieboldianoside B (3), and kizutasaponin K(12) (4).

Two new noroleanane-type triterpenoid saponins from the stems of Stauntonia chinensis.

Two new noroleanane-type triterpenoid saponins, 3ß,20α,24-trihydroxy-29-norolean-12-en-28-oic acid 24-O-ß-L-fucopyranosyl-(1→2)-[ß-D-xylopyranosyl-(1→3)]-ß-D-glucopyranoside (1) and 3ß,20α,24-trihydroxy-29-norolean-12-en-28-oic acid 24-O-ß-D-glucopyranosyl-(1→2)-[α-L-arabinopyranosyl-(1→3)]-ß-D-glucopyranoside (2) were isolated from the stems of Stauntonia chinensis DC., together with three known compounds, brachyantheraoside B2 (3), eupteleasaponin Ⅷ (4) and fargoside B (5). Their structures were elucidated by spectroscopic and chemical methods. The cytotoxic activities of compounds 1 and 2 were evaluated against five human tumor cell lines (HCT-116, HepG2, BGC-823, NCI-H1650, and A2780). Compounds 1 and 2 showed moderate cytotoxic activities toward the tested cell lines with IC50 values ranging from 12.71 to 32.04 µM.

The interplay of insulin resistance and beta-cell dysfunction involves the development of type 2 diabetes in Chinese obeses.

Type 2 diabetes mellitus (T2DM) is a heterogeneous disorder characterized by defects in insulin secretion and action and obesity plays an important role in the deterioration of glucose metabolism. In the present study we evaluated the degree of insulin resistance and first-phase insulin secretion of beta-cell in obese subjects with normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and T2DM in Chinese. A total of 220 subjects underwent standard 75 g oral glucose tolerance test (OGTT) and insulin-modified frequently sampled intravenous glucose tolerance test (FSIGT). Insulin sensitivity index (S I) was assessed by the reduced sample number (n = 12) of Bergman's minimal model method with FSIGT. Insulin secretion capacities were determined by the insulinogenic index (I 30 min - I 0 min)/(G 30 min - G 0 min) in OGTT and the acute insulin response to glucose (AIR) in FSIGT. The disposition index (DI), the product of AIR and S I was used to determine whether AIR was adequate to compensate for insulin resistance. The S I in healthy lean control group was significantly higher than that in NGT, IGT, and T2DM group, but there was no significant difference among NGT, IGT, and T2DM group. The AIR in NGT group was significantly greater than that in control group, but then it was progressively decreased in IGT and T2DM group. The value of DI in control group was significantly higher than that in those three abnormal groups, and was decreased from NGT to IGT and T2DM group with significant difference. It indicates that obese subjects with different glucose tolerances have a similar degree of insulin resistance but differ in insulin secretion in Chinese Han population.

Interleukin-18 enhances glucose uptake in 3T3-L1 adipocytes.

In order to characterize the potential causative effects of interleukin-18 (IL-18) on insulin resistance, we measured glucose uptake in 3T3-L1 adipocytes treated with mouse recombinant IL-18. IL-18 surprisingly enhanced, rather than reduced insulin-mediated glucose uptake in adipocytes. Moreover IL-18 could counteract the glucose uptake suppression caused by tumor necrosis factor alpha in 3T3-L1 adipocytes. The mechanism dissection showed that the IL-18 upregulated phosphorylated Akt and downregulated phosphorylated P38 MAPK. These findings indicated that the elevated serum IL-18 levels in obesity and diabetes might be a compensatory response to insulin resistance.

Hyperglycaemia after glucose loading is a major predictor of preclinical atherosclerosis in nondiabetic subjects.

OBJECTIVE: Carotid intima-media thickness (IMT) has proved to be an independent marker of preclinical atherosclerosis. The aim of this study was to determine whether carotid IMT is associated with the plasma glucose concentration in the fasting state, after loading with oral glucose, or with the insulin sensitivity index (ISI) in nondiabetic subjects with different levels of glucose intolerance and insulin resistance. DESIGN: Cross-sectional study. PATIENTS: A total of 160 nondiabetic subjects (147 from our obesity-overweight clinic and 13 healthy normal subjects) were included in the present study, among them 33 had normal glucose tolerance (NGT), 13 had impaired fasting glucose (IFG), 80 had impaired glucose tolerance (IGT) and 34 had both IFG and IGT. MEASUREMENTS: Carotid IMT was assessed in the common carotid artery by a high-resolution B-mode ultrasound system. Plasma glucose was measured after fasting and at 30 min, 1, 2 and 3 h after a standard 75-g load of glucose. The ISI was calculated from the frequent sampling intravenous glucose tolerance test (FSIGT). Results The IMT values in the NGT group were lower than those in the IFG, IGT and IFG + IGT groups (P < 0.03). No statistical difference in IMT values was found among the latter three groups. Univariate correlation analyses showed that the IMT was positively associated with age, plasma glucose concentrations 1 and 2 h after glucose loading, and serum concentration of low density lipoprotein (LDL) cholesterol (r=0.39, 0.22, 0.25 and 0.18, respectively, P<0.05). Multiple regression analysis showed that only age, plasma glucose concentration 2 h after glucose loading, and LDL cholesterol appeared to be significant correlates of the IMT (P<0.0001), whereas the ISI was not. CONCLUSIONS: In nondiabetic subjects with various degrees of glucose intolerance, there was a significant increase in IMT in those with IFG and IGT. Significant determinants of IMT, an indicator of preclinical atherosclerosis, include hyperglycaemia 2 h after a glucose load, age and LDL cholesterol, whereas fasting glucose concentration and the ISI were not significantly associated with IMT.

Elevated serum levels of interleukin-18 are associated with insulin resistance in women with polycystic ovary syndrome.

Overproduction of proinflammatory factors is associated with obesity and diabetes. Interleukin (IL)-18 as a member of IL-1 cytokine family is increased in obese, in diabetic, and even in polycystic ovary syndrome (PCOS) patients. In the present study we evaluated the association of serum IL-18 levels with insulin resistance in PCOS women. Forty-two PCOS women and 38 control subjects were enrolled in this study and matched with respect to age and body mass index (BMI). Serum IL-18 levels and hormones were measured for all subjects. Furthermore, euglycemic hyperinsulinemic clamp test was performed in selected 30 PCOS women and 11 control subjects. Serum IL-18 levels were elevated in PCOS women compared with the control (p = 0.033). IL-18 levels were positively correlated with homeostasis model assessment index (HOMA) beta index, which assesses beta cell function (p = 0.035), but were inversely correlated with clamp indices, which best represent insulin resistance status: M, Clamp ISI*100, and MCRg values (p = 0.006, 0.010, and 0.009 respectively). No correlation was found between IL-18 and age, BMI, waist-to-hip ratio (WHR), lipid profile, dehydroepiandrosterone-sulfate (DHEAS), sex hormone- binding globulin (SHBG), or fasting insulin levels. In conclusion, in the present study, serum IL-18 levels were significantly increased in PCOS women and firmly associated with insulin resistance displayed by euglycemic hyperinsulinemic clamp test. It indicates that IL-18 may be a contributing factor linking inflammation and insulin resistance in PCOS women.

Structure and functional analysis of unclassified genes strongly expressed in human visceral adipose tissue.

Our previous work has described the gene expression patterns of human visceral adipose tissue (VAT) at the transcriptome level and reported that the strongly expressed genes in VAT showed an uneven distribution throughout the genome. The aim of the present work was to focus on the unclassified genes and known expressed sequence tags (ESTs) strongly expressed in VAT and analyze their structure and function with bioinformatics. Among the 400 ESTs strongly expressed in the VAT, 340 clones were classified into known genes through searching the latest Genbank database. Functional classification showed that 85 clones were unclassified known genes, and approx 90% of them were found to be expressed in adipose tissue for the first time. Among the 85 unclassified genes, only two share similarities in the coding sequences with all species examined, and six genes had so far no obvious similarity to any genes across different species. The protein products of 7 genes had putative signal peptide and 11 had transmembrane domains. The protein products of 39 genes had relative specific motifs or prosites on primary structure. In silico Northern blot showed that 21 known ESTs were abundantly specifically expressed in adipose tissue, which may provide clues to identify novel genes closely related to adipocyte function with potential pathophysiological implications.

Chromosome localization analysis of genes strongly expressed in human visceral adipose tissue.

To understand fully the physiologic functions of visceral adipose tissue and to provide a basis for the identification of novel genes related to obesity and insulin resistance, the gene expression profiling of human visceral adipose tissue was established by using cDNA array. The characterization and chromosome localization of 400 expressed sequence tags (ESTs) strongly expressed in visceral adipose tissue were analyzed by searching PubMed, UniGene, the Human Genome Draft Database, and Location Data Base. Two hundred eighty-nine clones were classified into known genes among the 400 ESTs strongly expressed in the tissue. Among them, <20% have been previously reported to be expressed in adipose tissue. The chromosome localization of 389 ESTs strongly expressed in visceral adipose tissue showed that their relative abundance was significantly increased on chromosomes 1, 16, 19, 20, and 22 compared with the expected distribution of the same number of random genes. The intrachromosome distribution of the genes strongly expressed in visceral adipose tissue was concentrated in certain regions, such as 1p36.2-1p36.3, 6p21.3-6p22.1, 19p13.3 and 19q13.1. Among them, the region of 1p36.2-1p36.3 appeared to be specific for visceral adipose tissue. Interestingly, some genes playing an important role in the pathogenesis of insulin signal transduction and adipocyte differentiation, such as tumor necrosis factor-alpha and its receptors; CCAAT/enhancer-binding proteina; and phosphoinositide-3-kinase, regulatory subunit, polypeptide 2 (p85beta), were also localized in the concentrated regions, which may provide clues to identifying novel genes closely related to adipocyte function with potential pathophysiologic implications.

The gene expression profiling of human visceral adipose tissue and its secretory functions.

In order to fully understand the physiological functions of adipose tissue, especially its secretory functions, and to provide a basis for the identification of novel obesity related genes, the gene expression profiling of human visceral adipose tissue was established by using cDNA array. 33P-labelled cDNA, derived from visceral adipose tissue total RNA, was hybridized to a cDNA array containing over 16,000 expressed sequence-tagged clones which represent human singleton genes. The expressed sequence tag (EST) was considered to be expressed in visceral adipose tissue when the ratio of signal to noise was greater than or equal to 2. The results were analyzed with bioinformatics. Totally, 8230 genes were found to be expressed in visceral adipose tissue with 5200 known genes and 3030 known ESTs. Most of 84 secretory proteins, 120 receptors, and 74 transcription factors expressed in adipose tissue were newly identified. Many appetite-regulating related peptides or receptors and some reproduction-related genes were first found to be expressed in adipose tissue. Eight autocrine/paracrine systems were described for the first time in the visceral adipose tissue. These results clearly demonstrate that the visceral adipose tissue has important secretory functions and there is a complex local autocrine/paracrine regulatory network. The present work suggests that the visceral adipose tissue is an important component of the neuroendocrine-immune network and plays an important role in regulating appetite not only via endocrine but also via autocrine/paracrine systems. The visceral adipose tissue might also play a role in regulating reproduction and sexual function.