[Study on chemical constituents of Wedelia trilobata].

A new taraxer-based triterpenoid ester, taraxer-14-en-30-al-3ß-O-palmitate(1), was isolated from the whole plant of Wedelia trilobata, along with six known compounds, ent-kaur-16-en-19-oic acid(2), 16α-hydroxy-ent-kauran-19-oic acid(3), tara-xerol(4), ß-amyrin(5), 1ß-acetoxy-4α, 9α-dihydroxy-6ß-isobutyroxyprostatolide(6), and stigmasterol(7). Their structures were elucidated with use of a combination of spectroscopic techniques(IR, HR-ESI-MS, 1 D, 2 D NMR data) and chemical methods.

[Effects of aerobic exercise plus diet control on serum levels of total IGF-1 and IGF-1 binding protein-3 in female obese youths and adolescents].

OBJECTIVE: To investigate the effects of 4-week moderate aerobic exercise plus diet control on serum levels of total insulin-like growth factor 1(IGF-1) and IGF-1 binding protein-3 (IGFBP-3) as well as IGF-1 activity (reflected by molar ratio of IGF-1/IGFBP-3) in female obese adolescents and youths, and their possible role on fat loss, and improvement of glucose and lipid metabolism. METHODS: Nine female obese youths (age:18~19 y) and 30 female obese adolescents (age:14~16 y) were recruited and undertook 4-week aerobic exercise such as swimming and jogging (6 days/week, twice a day, 2 h/time with 5 min rest per 30 min exercise) with gradual increase of intensity from low (heart rate immediately post-exercise of 1st week:100~120 beats/min) to moderate (heart rate immediately post-exercise of 2nd-4th weeks:120~140 beats/min) level, combined with a diet intervention (total daily energy intake of 1 400 or 1 600 kcal according to basal metabolism rate) in Shanghai Dianfeng weight loss enclosed camp. Nine normal weight young women and 9 female children matched at age and nationality were recruited as the normal control. Before and after the experimental period, anthropometric index (body weight, body mass index(BMI) and waist circumference), glucose and lipid metabolism parameters including fasting blood glucose (FBG), fasting insulin (FINS), homeostasis model assessment of insulin resistance (HOMA-IR), triglyceride (TG); total cholesterol (TC), low density lipoprotein (LDL) and high density lipoprotein (HDL), and serum levels of total IGF-1 and IGFBP-3 were measured, and IGF-1 activity was calculated in the obese and normal control female adolescents. RESULTS: ①Compared with normal control, the serum levels of total IGF-1 and IGFBP-3 were decreased in the female obese youths and adolescents, and IGF-1 activity was reduced only in the obese female adolescents. ②The serum level of IGFBP-3 was down-regulated and IGF-1 activity was up-regulated while no change of serum total IGF-1 was induced by 4-week moderate aerobic exercise plus diet control, accompanied with significant decreases of body weight, BMI and waist circumference as well as improvement of glucose and lipid metabolism in the female obese youths and adolescents. Except for a positive association between the increased IGF-1 activity and the decreased waist circumference was found in the female obese youths by Pearson's correlation analysis, there was no relation of the decreased IGFBP-3, the increased IGF-1 activity with the improvements of anthropometric index and glucose and lipid metabolism in female obese youths and adolescents. CONCLUSIONS: The serum level of IGFBP-3 was down-regulated and the IGF-1 activity was up-regulated by 4-week moderate aerobic exercise plus diet control in female obese youths and adolescents. The increase of IGF-1 activity might be associated with the exercise-plus-diet-induced decrease of waist circumstance in female obese youths.

Fentanyl Promotes Breast Cancer Cell Stemness and Epithelial-Mesenchymal Transition by Upregulating α1, 6-Fucosylation via Wnt/ß-Catenin Signaling Pathway.

Cancer pain is a common and severe complication of human breast cancer, and relieving pain is fundamental strategy in the treatment. Fentanyl, as an opioid analgesic, is widely used in breast cancer patients. However, little is known about its effects on stemness and epithelial-mesenchymal transition (EMT) of breast cancer cells. Aberrant protein glycosylation is involved in cancer malignancy. The α1, 6-fucosylation is an important type of glycosylation, and the elevated α1, 6-fucosylation catalyzed by fucosyltransferase VIII (FUT8) is found in many tumors. However, whether 1, 6-fucosylation is involved in regulating stemness and EMT, and stimulated by fentanyl is not clear. In this study, we found that fentanyl induced stemness and EMT in MCF-7 and MDA-MB-231 breast cancer cells by analysis of sphere formation, expression of stemness markers (Sox2, Oct4) and EMT markers (N-cadherin, E-cadherin and Vimentin). Results also showed that fentanyl upregulated FUT8 gene and protein expression by qPCR, Western blot and immunofluorescent staining, as well as α1, 6-fucosylation level by Lectin blot and Lectin fluorescent staining. Furthermore, decreased or blocked α1, 6-fucosylation by FUT8 siRNA transfection or LCA Lectin blockage reduced stemness and EMT. Additionally, fentanyl activated the key molecules and target genes in Wnt/ß-catenin signaling pathway. LGK-974 (an inhibitor of Wnt ligands) suppressed fentanyl-mediated upregulation of α1, 6-fucosylation, stemness and EMT. The results of tumor xenograft demonstrated that fentanyl enhanced tumor growth, α1, 6-fucosylation, stemness and EMT. Taken together, our study reveals that fentanyl upregulated FUT8 expression, which increased α1, 6-fucosylation level through activation of Wnt/ß-catenin signaling pathway, thereby, induce stemness and EMT of breast cancer cells. This study suggest a potential side effect of fentanyl in the treatment of cancer, which may guide the safety of fentanyl in the clinical application.

[Effects of aerobic exercise and dieting on chemerin and its receptor CMKLR1 in the livers of type 2 diabetic rats].

OBJECTIVE: To investigate the effects of aerobic exercise and dieting on chemerin and its receptor chemokine like receptor-1 (CMKLR1) in the livers of type 2 diabetes mellitus (DM) rats and its possible roles on the improvements of blood glucose and lipid metabolism. METHODS: Fifty male SD rats were randomly divided into control group (Con, n=6) fed with normal diet and DM model group (n=44) fed with high fat diet. After 8-week feeding, DM model rats were intraperitoneal injected streptozocin (STZ) at the dose of 30 mg/kg body weight to establish DM rats. The successfully established diabetes rats were randomly divided into 4 groups (n=6):diabetes control group (DM), diabetes exercise group (EDM), diabetes dieting group by feeding normal diet (NDM) and diabetes exercise plus dieting group (ENDM). During the following 4 weeks, exercise rats participated in moderate intensity aerobic exercise on a treadmill with a progressing increasing load for 4 weeks. Fasting blood glucose (FBG) was determined by Roche glucometer. Serum levels of triglyceride (TG), total cholesterol (TC) and low-density lipoprotein (LDL)) were detected by using full automatic biochemical analyzer. The mRNA and protein expressions of chemerin and CMKLR1 in the livers were detected by real time PCR and Western blot, respectively. RESULTS: Accompanied with the increased serum levels of TC, TG, LDL and FBG in DM rats, the mRNA and protein levels of chemerinand CMKLR1 in the livers of DM rats were significant up-regulated. The serum levels of TC, TG, LDL and FBG were reduced in EDM, NDM and ENDM rats compared with those of DM rats, meanwhile,decreased protein levels of chemerin were found in the livers of EDM, NDM and ENDM rats with most significant in ENDM rats while increased protein levels of CMKLR1 in the livers of NDM and ENDM rats. CONCLUSIONS: Four weeks of aerobic exercise with or without dieting decreased chemerin and increased CMKLR1 in the livers of DM rats at the protein levels, which might be attributed to the improvement of blood glucose and lipid metabolism of DM rats.

The clinicopathologic significance of the loss of BAF250a (ARID1A) expression in endometrial carcinoma.

OBJECTIVE: AT-rich interactive domain 1A (ARID1A) is a tumor suppressor gene that encodes the BAF250a protein. Recent studies have shown the loss of ARID1A expression in several types of tumors. We aimed to investigate the clinical and pathologic role of BAF250a in endometrial carcinoma. METHODS: We examined the expression of BAF250a and its correlation with the expression of p53, estrogen receptor, progesterone receptor, glucocorticoid receptor, hypoxiainduciblefactor-1α, and vascular endothelial growth factor in normal and various malignant endometrial tissues. RESULTS: The expression of BAF250 was significantly down-regulated in endometrial carcinoma when compared with normal endometrial tissues. The loss of BAF250a expression was found in 25% of endometrial carcinoma samples but not in normal endometrial tissues, complex endometrial hyperplasia, and atypical endometrial hyperplasia samples. Subtypes of endometrial carcinoma, especially uterine endometrioid carcinoma and uterine clear cell carcinoma, had higher frequency of loss of BAF250a expression. In addition, the expression of BAF250a was positively correlated with estrogen receptor and negatively correlated with p53 in poorly differentiated endometrial adenocarcinoma. Moreover, the expression of BAF250a was significantly associated with the differentiation status of endometrial carcinoma but not associated with clinical stage, the depth of myometrial invasion, lymph node metastasis, and overall survival of patients with endometrial carcinoma. CONCLUSIONS: Our data showed that loss of BAF250a is frequently found in high-grade endometrioid and clear cell carcinomas but not in other types of endometrial carcinoma. The loss of BAF250a expression does not have prognostic value for endometrial carcinoma.

[The application and research progress of functional magnetic resonance imaging in glaucoma].

Recent advances on functional magnetic resonance technology have greatly broadened its application in many disciplines including ophthalmic research area. Functional magnetic resonance imaging(fMRI), which combines the anatomical and functional features of the neural system, is a non-invasive,objective and orienting method. Among so many sub-methods, blood oxygenation level dependent MRI reflects the neural activities of visual cortex; diffusion tensor imaging traces nerve fibers; gadolinium enhanced MRI could access blood-ocular barrier function; manganese enhanced MRI reveals axoplasmic transport and retinotopic projection to sub-cortical nucleus; blood volume MRI could evaluate lamina-specific hemodynamics of ocular wall; while magnetic resonance spectroscopy investigates the molecular metabolism in nerve system. Glaucoma may damage the whole visual pathway, and fMRI would helps us estimate the in vivo fiber integrity and visual functional status quo in glaucoma patients. Here we first review the basic principles of several fMRI techniques and then discuss the applications in research related to glaucoma.