Prevalence of maturity-onset diabetes of the young in phenotypic type 2 diabetes in young adults: a nationwide, multi-center, cross-sectional survey in China / 中华医学杂志(英文版)

BACKGROUND@#Maturity-onset diabetes of the young (MODY) is the most common monogenic diabetes. The aim of this study was to assess the prevalence of MODY in phenotypic type 2 diabetes (T2DM) among Chinese young adults.@*METHODS@#From April 2015 to October 2017, this cross-sectional study involved 2429 consecutive patients from 46 hospitals in China, newly diagnosed between 15 years and 45 years, with T2DM phenotype and negative for standardized glutamic acid decarboxylase antibody at the core laboratory. Sequencing using a custom monogenic diabetes gene panel was performed, and variants of 14 MODY genes were interpreted as per current guidelines.@*RESULTS@#The survey determined 18 patients having genetic variants causing MODY (6 HNF1A , 5 GCK , 3 HNF4A , 2 INS , 1 PDX1 , and 1 PAX4 ). The prevalence of MODY was 0.74% (95% confidence interval [CI]: 0.40-1.08%). The clinical characteristics of MODY patients were not specific, 72.2% (13/18) of them were diagnosed after 35 years, 47.1% (8/17) had metabolic syndrome, and only 38.9% (7/18) had a family history of diabetes. No significant difference in manifestations except for hemoglobin A1c levels was found between MODY and non-MODY patients.@*CONCLUSION@#The prevalence of MODY in young adults with phenotypic T2DM was 0.74%, among which HNF1A -, GCK -, and HNF4A -MODY were the most common subtypes. Clinical features played a limited role in the recognition of MODY.

Advances in immunoporosis / 中华内分泌代谢杂志

Osteoporosis is a common metabolic bone disease, which is involved in disrupted normal bone remodeling process and bone resorption exceeding bone formation. Osteoblasts and osteoclasts play critical roles in maintaining bone homeostasis. In recent years, more and more studies have found that immune cells are involved in the regulation of osteoblast and osteoclast activity via releasing various chemokines and cytokines, and the concept of immunoporosis has been proposed accordingly. This article summarizes the current state of knowledge on the immune system in the pathophysiology of osteoporosis, so as to study and prevent osteoporosis from the perspective of immunology.

Research progress of long noncoding RNA in regulating adipogenesis / 中南大学学报(医学版)

Long noncoding RNA (lncRNA) is once thought to be the genome transcriptional "noise". However, it has received considerable attention in the past few years and is emerging as potentially important player in biological regulation. Recent studies have revealed that increasing number of lncRNA plays pivotal roles in regulating the gene expression which involves in the development of the human disease. Functions of lncRNA include 3 types of interaction: RNA-RNA, RNA-DNA, and RNA-protein, which may participate in gene expression regulation through epigenetic modifications, transcriptional regulation, post-transcriptional regulation, acting as biological media. Due to the prevalence of obesity and related diseases, some attempts have been done to explore the pathogenesis of obesity from the field of noncoding RNA. Several lncRNAs have been identified to be involved in the regulation of the adipogenesis (white adipose tissue and brown adipose tissue) and energy metabolism. In this review, we summarized recent advances of lncRNAs to provide a new sight for the mechanism of obesity.

The effect of diabetes on the bone metabolism / 中国医师杂志

The relationship between diabetes and osteoporosis has gradually become a new research hotspot , but is still much controversy .High concentration of blood glucose can be bond to varieties of proteins in vivo and form glycosylation end products in col -lagen tissue and reduce bone strength , besides it can inhibit RANKL induced osteoclast formation and bone resorption by repressing redox-sensitive NF-kappa B activity .A series of diabetes mellitus complications can induce less local bone nutrition supply and calcium and phosphorus sorption , reduce muscle tension and bone mineral density , which leads to the increase of fracture risk .Type 2 diabetes patients with overweight or obesity often have increased secretion of inflammation factors , adiponectin and leptin , which promotes the formation of osteoclasts and encourages bone marrow stromal stem cells to differentiate into adipocytes ;On the other hand , adiponectin and leptin can facilitate osteoblasts proliferation , differentiation and activity , and promotes bone formation .This article will discuss how diabetes works on bone metabolism and the underlying pathophysiological and physiological mechanism .

Transcriptomic regulation and molecular mechanism of polygenic tumor at different stages / 中南大学学报(医学版)

The research team on the National Key Scientific Program of China: "Transcriptomic regulation and molecular mechanism research of polygenic tumor at different stages" has focused on the field of transcriptomics of 4 common polygenic tumors, including nasopharyngeal carcinoma(NPC), breast cancer, colorectal cancer, and glioma. Extensive laboratory work has been carried out on the expression and regulation of tumor transcriptomics; identification of tumor suppressor/susceptible genes; mechanism of tumor epigenetics including miRNAs, and comparative study of specific gene/protein cluster of tumor transcriptomics and proteomics. Genes including SPLUNC1, LTF, BRD7, NOR1, BRCA1/2, PALB2, AF1Q, SOX17, NGX6, SOX7, and LRRC4 have been identified as the key transcriptional regulation genes during the stage of tumor initiation and invasion. Accordingly,the NPC gene signal regulation network of "SPLUNC1-miR-141-target genes", the breast cancer interaction signal pathway of "miR-193b-uPA",the glioma signal network of "miR-381- LRRC4-MEK/ERK/AKT", and the miRNA-target gene network of colorectal cancer metastasis related gene NGX6 have been thoroughly elucidated. These fruitful Results imply that the changes of key molecules in crucial signal pathway will cause severe dysfunction in signal transduction and gene regulation network in polygenic tumors, indicating that in the category of pathogenesis,these tumors may further classify as the "Disease of gene signal transduction and gene regulation network disorder". The researches have laid solid foundation for revealing the molecular mechanism and transcriptomic regulation of polygenic tumors at different stages.

Effect of nylestriol and levonorgestrel on the expression of estrogen receptor subtypes in human osteosarcoma MG-63 cell lines / 中南大学学报(医学版)

OBJECTIVE@#To observe the effect of different concentrations of nylestriol (NYL) and levonorgestrel (LNG) on the expression of ERα and ERβ in human osteoscarcoma MG-63 cell lines, and to explore the impact of paracrine effect on the gene expression.@*METHODS@#MG-63 cells were treated with 3 concentrations (10(-10),10(-8), and 10(-6) mol/L) of NYL or LNG. The untreated control group and the positive control group were also established. The 2 groups treated with NYL (10(-10) mol/L) or LNG (10(-8) mol/L) were designed to renew the medium every 12 h. Semi-quantitative RT-PCR was conducted to detect the mRNA expression of ERα and ERβ on the MG-63 cells treated with different concentrations of the 2 drugs, respectively.@*RESULTS@#Both drugs up-regulated ERα and ERβ mRNA expression. The best concentration for both NYL and LNG was 10(-6) mol/L for ERα expression. As for ERβ, the best concentration of NYL and LNG was 10(-10) mol/L and 10(-8) mol/L. The role of medium replacement on the expression of ERα was not observed, but medium replacement inhibited ERβ expression.@*CONCLUSION@#Both NYL and LNG can up-regulate the mRNA expression of ER subtypes in MG-63 cells, with mutual restriction between the 2 subtypes. The paracrine effect on MG-63 cell lines may be involved in the regulation process of mRNA expression of ERβ.

Taurine stimulates osteoblast differentiation via ERK1/2 signal pathway / 中华内分泌代谢杂志

This in vitro study demonstrated that taurine supplemented culture medium enhanced alkaline phosphatase (ALP) activity, osteocalcin secretion and mineralized matrix formation. Taurine induced activation of ERKI/2 and osteoblast differentiation, which was blocked by pretreatment of osteoblasts with ERKI/2 inhibitor (PD98059), suggesting taurine stimulated osteoblast differentiation via ERKI/2.

17 beta-estradiol versus progesterone in the expression of osteoprotegerin gene in human osteoblast-like cells / 中国组织工程研究

BACKGROUND:Estrogen/progestins replacement therapy prevents excess bone loss in postmenopausal women.Recently osteoprotegerin (OPG) has been identified in osteoblast and displayed to inhibit bone resorption.OBJECTIVE: To compare the action between 17β-estradiol (E2) and progesterone on OPG expression in cultured normal human osteoblast-like cells (hOB).DESIGN: A comparative investigation.SETTING: Institute of Metabolic Endocrinology, the Second Xiangya Hospital of Central South University.MATERIALS: α-MEM (Sigma Chemical Corp., St. Louis, MO, USA); Type Ⅳ collagenase (Sigma); Fetal bovine serum (Gibco-BRL Corp., Grand Island, NY, USA); Osteocalcin radioimmunoassay kit (DiaSorin Corp., Stillwater, MN, USA).METHODS: The experiments were carried out in the Institute of Metabolic Endocrinology, Second Xiangya Hospital of Central South University from January 2003 to March 2006. The osteoblasts were extracted from the cancelous bone of anterior superior iliac spine of normal people, then cultured. The hOB were treated with E2 and progesterone, and the expressions of OPG mRNA and OPG protein were determined by Northern blot analysis and enzyme-linked immunoabsorbent assay (ELISA) respectively.MAIN OUTCOME MEASURES: ①Characterization of human osteoblast-like cells; ②Effect of E2 and progesterone on OPG mRNA levels by Northern blot analysis; ③ Effect of E2 and progesterone on OPG protein levels in the conditioned medium by ELISA.RESULTS: ① Characterization of hOB in vitro The ALP levels in normal human osteoblasts were (74.3±4.7) U/g protein,and the detectable osteocalcin levels was (3.84±0.39) μg/L protein], which suggested that osteoblasts were the primary cell type found in our bone-derived cell cultures from donors. ② Effects of E2 and progesterone on the levels of OPG mRNA by Northern blot analysis: The OPG mRNA band was week in the control group [(12.3±3.5)%], treatment with 1 × 10-10, 1 ×10-9 1 ×10-8 mol/L E2 caused an increase in the levels of OPG mRNA. The expression of OPG mRNA in the 1×10-8 mol/L E2 group was gradually increased at 12, 24 and 48 hours. Progesterone had no influence on OPG mRNA expression. ③ Effects of E2 and progesterone on OPG protein production in conditioned medium determined with ELISA:ELISA revealed that treatment with 1 ×10-10, 1 ×10-9, 1 ×10-8 mol/L E2 induced obvious increase in the levels of OPG protein in cells media as compared with that in the control group [(1.27±0.26), (2.34±0.35), (3.62±0.23), (0.64±0.14)μg/L, P ＜ 0.01]. In the presence of 1×10-8 mol/L E2, OPG protein production in cells media at 12, 24 and 48 hours were significantly higher than that in the control group [(1.30±0.30), (3.07±0.14), (3.50±0.33), (0.62±0.12) μg/L, P ＜ 0.01]. 1 × 10-10, 1 ×10-9 1 × 10-8 mol/L progesterone had no influence on the OPG protein production after 12-24 hours (P ＞ 0.05).CONCLUSION: The different regulation of OPG production in osteoblasts by E2 and progesterone may contribute to the mechanisms by which estrogen or progestins exerts its different action on bone resorption.

The Molecular Mechanism Involved in The Development of Nasopharyngeal Carcinoma / 生物化学与生物物理进展

Nasopharyngeal carcinoma (NPC) is a polygenetic inheritance tumor. It has very high incidence in southern China and among immigrants and their offspring from south Chinese, and has done a great harm to the health of south Chinese. As a malignant tumor with obvious tendency of familial aggregation and regional difference, it is suggested that the etiology and pathogenesis of NPC are relevant to the coeffects of genetic and environmental factors. It is the main point to focus on the elucidating of the pathogenesis of PNC as a polygenetic inheritance tumor, primarily establishing of the concept of susceptibility gene groups in NPC and the carcinogenesis model of the multi-step Domino effect involved in the molecular mechanisms of NPC dominated by susceptibility gene groups in order to lay out a substantial foundation for finding the high-risk susceptibility factors of NPC, screening the high-risk population of NPC and exploring the targetic and individual measures in diagnosis and treatment of NPC.

Expression and role of adrenomedullin and its receptor in patients with chronic obstructive pulmonary disease / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To investigate the expression and role of adrenomedullin (ADM) and adrenomedullin receptor (ADMR) in patients with chronic obstructive pulmonary disease (COPD).</p><p><b>METHODS</b>Small pulmonary artery remodeling was observed using morphometric analysis. The expression of ADM and ADMR mRNA in lung tissue was calculated by in situ hybridization in 9 COPD cases. Cardiac catheterization was performed in 22 COPD cases to monitor changes of hemodynamic parameters and patients were divided into two groups based on mean pulmonary artery pressure (mPAP). The cases without pulmonary hypertension (PH) were placed in Group A (n = 12) and those with PH were placed in Group B (n = 10). The levels of pulmonary arterial plasma ADM were measured by radioimmunoassay. Blood gas analysis was also conducted.</p><p><b>RESULTS</b>The ratio of vascular wall thickness to external diameter (MT%) and the ratio of vascular wall area to total area (MA%) were higher in patients with COPD (P < 0.01). In situ hybridization showed that ADM mRNA and ADMR mRNA were expressed in the pulmonary artery walls of control subjects. The expression levels were significantly higher in those of COPD sufferers (P < 0.01). Statistically positive relationships were visible between ADM and ADMR, and the plasma ADM level of Group B was significantly higher than that of Group A (P < 0.05). The plasma ADM level had a significantly positive correlation to mPAP and pulmonary vascular resistance (PVR), while being negatively correlated to levels of PaO(2).</p><p><b>CONCLUSION</b>ADM may play an extremely protective role as a local autocrine/paracrine factor in COPD.</p>

The synergistic action of estradiol and L-ascorbic acid on the osteoblast-like cell line MG-63 / 中华老年医学杂志

Objective To observe the synergistic action of 17? estradiol(E 2) and L ascorbic acid on the activity of alkaline phosphatase (ALP), cell proliferation and gene expression in osteosarcoma MG 63 cell line, and to study the mechanism of E 2 in treating osteoporosis. Methods MG 63 cells were treated with 10 8 mol/L E 2 with or without 100 ?g/L L ascorbic acid, and then the ALP activity was determined by using ? nitrophenyl phosphate as a substrate. Cell proliferation was measured by ( 3H) thymidine( 3H TdR) incorporation method. mRNA expression of type I collagen, matrix metalloproteinase 1(MMP 1), MMP 2 and osteoprotegerin(OPG) was detected by semiquantitative RT PCR method. Gelatin zymogram was used for the assay of MMP 2 activity. The synergistic action of E 2 and L ascorbic acid on MG 63 cell lines could be evaluated basing on the above indexes since they stand for separately the cell proliferation, gene expression and cell differentiation. Results The action of combined treatment with E 2 and L ascorbic acid on MG 63 cells was obviously stronger than the action using single E 2 or single L ascorbic acid. E 2 and L ascorbic acid increased the ALP activity to 200% ( P

Effects of Insulin on the Gene Expression of Insulin Receptor Substrate-2 in MG-63 Cells / 中国医师杂志

Objective To investigate the effects of insulin on the mRNA expression of insulin receptor substrate-2 (IRS-2) in MG-63 cells. Methods Semi-quantitative RT-PCR was used to study the action of insulin on the mRNA expression of IRS-2 in MG-63 cells. Results Insulin regulated the mRNA expression of IRS-2 in a dose- and time-dependent manners in MG-63 cells. Insulin up-regulated the expression of IRS-2 mRNA at 10~ -10～10~ -6mol/L(P

The Expression of Insulin Receptor Substrate in Human Osteoblast / 中国医师杂志

Objective To determine the expression of insulin receptor substract(IRS) family in human osteosarcoma cell line MG-63 and cultured normal human osteoblast-like cells (HOB). Methods The mRNA and protein expression of IRS family was measured using semi-quantitative RT-PCR and western blot analysis, respectively. Results MG-63 cells and HOB had the mRNA and protein expressions of IRS-1,-2,-3, and -4. Among IRS family, the expressions levels of IRS-1 mRNA and protein were the highest, and those of the IRS-4 mRNA and protein were the lowest in MG-63 cell line and HOB. Conclusion MG-63 and HOB can express the mRNA and protein of IRS family members, and the expressional levels of IRS family members were different.

Effect of 17?-estradiol (E_2) on the gene expression of osteoprotegerin in human osteoblast and MG-63 cells / 中华内分泌代谢杂志

Objective To investigate the effects of 17 ? estradiol (E 2) on the gene expression of osteoprotegerin (OPG) in human osteoblast (HOB) and MG 63 osteosarcoma cell lines at various maturity stages of cultures, and to make a better understanding of the mechanism of E 2 deficient osteoporosis. Methods The activities of alkaline phosphatase (ALP), osteocalcin (OC) secreted by cultured cells at different stages of cell proliferation, maturity and collagen mineralization, as well as the effect of E 2 on the OPG gene expression were determined. HOB was prepared from ilial bone tissue in adults, OPG gene expression was quantified by RT PCR, and the activity of ALP, OC was corrected with Bradford′s method. Results For both kinds of cells, expression of OPG at the 12th days′ culture reached the highest levels without any treatment, and 10 -8 mol/LofE 2increasedOPGmRNA to a maximum of about 10 times (P

Signal transduction pathways of 17?-estradiol-induced MT1-MMP expression in MG63 cells / 中华内分泌代谢杂志

Objective To investigate the signal transduction pathways related to 17?-estradiol-induced membrane type-1 matrix metalloproteinase (MT1-MMP) expression in human osteosarcoma cell line MG63. Methods MG63 cells were incubated with ICI 182 780 for 48 h, then exposed to different concentrations of ICI 182780, 17?-estradiol, and specific antagonists H-89, H-7, PD98059, SB203580, genistein and PTDC of protein kinase (PK) A、PKC、extracellular signal-regulated kinase (ERK)、p38MAPK、protein tyrosine kinase (PTK) and nuclear factor (NF)-?B. The MT1-MMP level was determined by Western blotting and immunohistochemistry. Results Western blotting showed that MT1-MMP level was increased in 17?-E_2 group and decreased in PDTC and genistein groups, and immunohistochemistry revealed that MT1-MMP was located in cytoplasm and cellular membrane, but not in nucleus. Conclusion 17?-estradiol regulates MT1-MMP expression mainly through NF-?B and PTK pathways in MG63 cells.