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Objective:To evaluate the effect of short-term very low-calorie restriction(VLCR) on glycemic control in overweight/obese patients with type 2 diabetes, and to explore mechanisms through identifying markers of gut microbiota.Methods:This trial was conducted in 14 adult overweight/obese patients with type 2 diabetes. They received VLCR for 9 days in the hospital(calorie intake 300-600 kcal/d). Before and after VLCR, body weight(BW), waist circumference(WC), blood pressure(BP), and heart rate(HR) were measured, and body mass index(BMI) was calculated according to their height and weight. Fasting blood glucose(FBG), 2 h postprandial blood glucose(2hPBG), fasting insulin(FINS), triglycerides(TG), total cholesterol(TC), high-density lipoprotein-cholesterol(HDL-C), and low-density lipoprotein-cholesterol(LDL-C) were determined, and yielded the homeostasis model assessment for insulin resistance(HOMA-IR). Additional lab tests such as liver and kidney function and electrolytes were performed. The estimated glomerular filtration rate(eGFR) was calculated to evaluate renal function. All data were analyzed using the SPSS Sample Power software. Feces samples were collected before and after VLCR. Fecal samples were tested for microbial diversity using 16S rDNA technology. Professional software was used to analyze the differences of gut microbiota in feces before and after VLCR.Results:After 9 days of VLCR, BW, BMI, WC, BP, HR, FBG, 2hPBG, FINS, HOMA-IR, alkaline phosphatase, TG, and blood urea nitrogen of 14 overweight/obese patients with type 2 diabetes were significantly reduced( P<0.05). No effect was seen on serum alanine aminotransferase, aspartate amino transferase, gamma glutamyl transferase, TC, HDL-C, LDL-C, creatinine, eGFR, uric acid, albumin, calcium, and phosphorus( P>0.05). The gut microbiota diversity did not differ before and after VLCR. The abundance of Bacteroidetes increased significantly, and the Firmicutes/Bacteroidetes ratio decreased from 11.79 to 4.20. Between groups analysis showed the abundance of Parabacteroides distasonis increased significantly after VLCR. Conclusion:VLCR can improve body weight and glucose and lipid metabolism in overweight/obese patients with type 2 diabetes, with no serious adverse events. Parabacteroides distasonis may be a marker of VLCR.
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Circular RNA (circRNA) is a ubiquitous class of noncoding RNAs (ncRNAs) in all kingdoms of life with diverse structures.CircRNA is an endogenous noncoding RNA molecule with covalently close cyclic structure which does not have 5'end cap and 3'poly (A) tail.It is found to be evolutionary conservative and stable with tissue specificity.CircRNAs have many biological functions.In addition to acting as miRNA sponges,many other functions are being revealed,including regulator of gene transcription,and splicing and protein translation.It is involved in ovarian epithelial neoplasms,pre-eclampsia and other development.CircRNAs could regulate the expression of numerous gynecological cancer-related microRNA (miRNAs).The circRNA-miRNA-messenger RNA(mRNA) axis is a known regulatory pattern of several cancer-associated pathways,with both agonist and antagonist effects on carcinogenesis.Numerous studies have shown that circRNAs may become potential targets and clinical diagnostic markers for reproductive and gynecological diseases.This review focuses on the biogenesis and properties of circRNAs,databases of circRNA,their functions and potential significance in gestational,tumor and gestational diseases.
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Objective To investigate the effect of metformin on the growth of human anaplastic thyroid cancer cell HTh74Rdox which is doxorubicin resistant. Methods The HTh74Rdox was treated with different concentrations of metformin for 48 h. Cell morphology was observed by microscope, cell viability was tested by methylthiazoletetrazolium (MTT), cell apoptosis by annexin Ⅴ and propidium iodide double staining, the anti-oncogenic miRNA was assayed by realtime fluorescence quantitative PCR (RT-PCR), and the adenosine monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signaling pathway tested by western blot. Furthermore, the anti-oncogenic miRNAs were knockdown by miRNA inhibitors (miR-34a, miR-101, miR-125b, and miR-138 inhibitors) and the cells were treated by metformin for 48 h, after that, cell apoptosis was detected by annexin Ⅴ and propidium iodide double staining, the expression of protein related to AMPK/mTOR signaling pathway was detected by western blot. Results Metformin inhibited the growth of human anaplastic thyroid cancer cell HTh74Rdox in a concentration-dependent manner, the cell apoptosis was induced by metformin, and there was a significantly lower expression of miR-34a, miR-101, miR-125b, and miR-138 in the HTh74Rdox. However, the four above miRNAs were upregulated by metformin, and AMPK/mTOR pathway was also activated by metformin. When these miRNAs were suppressed by miR-inhibitors (miR-34a, miR-101, miR-125b, miR-138 inhibitors), the stimulating effect of apoptosis and AMPK/mTOR pathway by metformin were reversed. Conclusion Metformin significantly suppresses cell viability of human anaplastic thyroid cancer cell HTh74Rdox, and stimulates AMPK/mTOR pathway and apoptosis by upregulating the expressions of miR-34a, miR-101, miR-125b, miR-138 in HTh74Rdox cell.
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Objective Inflammation is a defensive reaction of body , but excessive inflammatory response can lead to physi-cal injury.The aim of this study was to explore the effects of luteolin on the secretion of inflammatory cytokines from lipopolysaccharide (LPS) and interferon-g(IFN-γ) activated RAW264.7 cells. Methods RAW264.7 cells were divided into 5 groups: control group (without any medicine), M1 group (polarized M1 cells activated by final concentration of 10 ng/mL LPS+20 ng/mL IFN-γ), M1+5L group (simultaneous activation of LPS and IFN-γplus final concentration of 5μmol/L luteolin), M1+10L group(simultaneous activa-tion of LPS and IFN-γplus 10μmol/L luteolin), M1+20L group(simultaneous activation of LPS and IFN-γplus 20μmol/L luteolin). The cell morphological transformation was observed by laser confocal microscope ;the mRNA levels of iNOS , IL-1βand IL-6 were test-ed by real-time quantitative PCR respectively;the secretion levels of TNF-αand IL-6 in culture supernatant were detected by ELISA;the changes of p-STAT3 (ser727) protein pathways were examined by western blot. Results Cellular morphology of activated RAW 264.7 cells changed obviously .Compared with the control group , the mRNA levels of iNOS, IL-1βand IL-6 decreased significantly in the other 4 groups(P<0.05).The iNOS level in M1+20L group significantly de-creased compared with M1 group[(29.52±3.07) vs (98.91±10.65), P<0.01].As to IL-1βlevel, it decreased significantly in M1+10L group(78.38±8.65) and M1+20L group(41.59±6.80) compared with M1 group(110.69±4.12)(P<0.05).While the IL-6 levels decreased significantly in M1+5L group(177.51±19.28), M1+10L group (106.14±5.63), M1+20L group(27.15±1.26), compared with M1 group(394.10±33.47)(P<0.05).LPS+IFN-γcould induce in-creased p-STAT3 (ser727) expression in M1 phenotype of RAW264.7 cells which was proved by its significant increase in M 1 group, M1+5L group and M1+10L group compared with control group (P<0.05).In comparison to M1 group, p-STAT3-ser expression in M1 phenotype downregulated in M1+5L group, M1+10L group, M1+20L group(P<0.05), along with dose-dependent characteristic.Com-pared with control group, the levels of IL-6 and TNF-αincreased significantly in M1 group, M1+5L group and M1+10L group.Com-pared with M1 group, the levels of IL-6 and TNF-αdecreased significantly in M1+5L group, M1+10L group and M1+20L group(P<0.05) , in which IL-6 showed concentration independence and TNF-αshowed no concentration independence . Conclusion Luteolin inhibits the secretion of pro-inflammatory cytokines through the down-regulation of p-STAT3 so as to exert anti-inflammatory effects .
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OBJECTIVE:To investigate the cognition,evaluation and demands of medical staff to the clinical pharmacy work in the secondary and tertiary medical and health institutions in Xi’an city,and provide reference for further promoting the develop-ment of the local clinical pharmacy work. METHODS:20 secondary and tertiary medical and health institutions in Xi’an city were randomly selected to conduct a random sampling questionnaire for physicians,nurses (senior nurses),pharmacists (non-clinical pharmacist)and other medical technicians. And the results were statistically analyzed. RESULTS:Totally 1 020 questionnaires were sent out,851 were effectively received with effective recovery of 83.4%. 45.9% respondents knew clinical pharmacy,and“Col-league”was the main channel;34.3% thought clinical pharmacy“only maintained normal operation. 74.7% surveyed medical staff,92.6% surveyed pharmacists and 70.6% surveyed physicians thought clinical pharmacists“should”take round with the doc-tors and nurses;44.3% respondents showed“dissatisfaction”and“general satisfaction”with the clinical pharmacy work in their hospitals. 48.5% respondents would take the initiative to consult the clinical pharmacist for medication;45.5% respondents partial-ly accepted the drug information provided by clinical pharmacists. There were significant differences in the investigation results in aspects of respondents’understanding level and channel for clinical pharmacy,cognition for development situation of clinical phar-macy,evaluation for clinical pharmacists participating round,demand for consulting the medication,acceptance for drug informa-tion provided by clinical pharmacists,and other items(P<0.05). CONCLUSIONS:The cognition and effect of clinical pharmacy work on medical staff need to be further strengthened,clinical pharmacists should also have solid clinical knowledge and the knowl-edge of medicine to meet the demand of medical staff in different positions,the acceptance of medical staff to the pharmaceutical care needs to be further improved. Clinical pharmacists should earnestly fulfill their job functions through various efforts to promote rational drug use.
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Objective To investigate the effect of 17β-estradiol on the proliferation of thyroid stem/ progenitor cells.Methods In thyroid stem/progenitor cells derived from nodular goiters,the effects of 17 β-estradiol on thyrosphere formation,estrogen receptor (ER) expression,cyclin D1 expression,and mitogen activated protein kinase (MPAK) pathway were analysed by BrdU ELISA,conventional and realtime PCR,immunofluorensence staining,and Western blot.Results 17β-estradiol induced thyrosphere formation and proliferation of thyroid stem/ progenitor cells.ER-α and ER-β were expressed in thyroid stem and progenitor cells with higher mRNA expression level of ER-α compared to differentiated thyrocytes (8.85-±0.81 vs 1.10 ±0.35,P＜0.01).Stimulation by 1 mmol/L 17β-estradiol increased cyclin D1 mRNA expression and ERK phosphorylation levels,which was blocked by an ER antagonist,ICI 182780.Conclusion Estrogen stimulated the growth of stem cells derived from thyroid nodules via estrogen receptor,suggesting the relevance of increased thyroid stem cell proliferation with higher prevalence of thyroid nodules in women.
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Objective To elucidate the effect of multi-kinase inhibitor sorafenib on anaplastic thyroid carcinoma cells in the presence or absence of metformin.Methods SW1736 and C643 cells were treated with sorafenib in the presence or absence of metformin for various periods of time.Cell viability was detected by MTT.Cell cycle and cell apoptosis were measured by flow cytometry.Caspase-3 activity was detected by colorimetric kit.Western blot was used to analyze pERK phosphorylation and cyclinD1 expression.Results Sorafenib inhibited the growth of anaplastic thyroid carcinoma cells and induced cell cycle arrest and cell apoptosis.The EC50 of sorafenib in SW1736 and C643 was 3.68 μmol/L and 4.87 μmol/L respectively.After sorafenib ± metformin treatment,the caspase3 activity was 131.5 ％ and 278.0％ (P＜0.01) in SW1736 cells,127.2％ and 196.6％ (P＜0.01) in C643 cells.On the molecular level,sorafenib inhibited the phosphorylation of ERK and decreased the expression of cyclinD1.Metformin amplified the growth inhibitory effect of sorafenib on anaplastic thyroid carcinoma cells.The cell viability was 0.76 ± 0.17 and 0.30 ± 0.04 (P＜0.01) in SW1736 cells,0.72 ± 0.09 and 0.34 ± 0.10 (P＜0.001) in C643 cells after 2.5 μmol/L sorafenib without or with 5 mmol/L metformin treatment.Conclusions The combination of sorafenib and metformin may be a potent strategy for the treatment of anaplastic thyroid carcinoma and other advanced cancers.
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The residents who had lived for at least 5 years and aged over 20 years old were sampled from urban to rural districts of Jiangsu Province with a stratified cluster sampling technique. B mode ultrasonography and thyroid function determination were carried out in 6 128 persons. The location, diameter, number, boundary, and calcification in thyroid nodules were described by using 7.5 MHz/50 mm transducer of thyroid ultrasonography. TSH was measured by chemiluminescence immunoassay. Free triiodothyronine(FT3)and free thyroxin(FT4)were measured when TSH was abnormal. The crude prevalence of thyroid nodules was 21.12% in total population, 14.55% in male, and 25.24% in female. The standardized prevalence was 15.69%, 11.20%, and 20.40%, respectively. The prevalence was lower in male than in female, and increased with age(P＜0.05). Thyroid nodules in Jiangsu Province were highly prevalent and more attention should be paid to the follow-up, early diagnosis, and treatment.
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Objective To compare the effects of intermittent high blood glucose and consistent hilgh blood glucose on pancreatic islet β-cell function and β-cell apoptosis in GK rats.Methods Twenty-two male GK rats were randomly divided into 2 groups consisting of consistent hish blood glucose group(HG)and intermittent high blood glucose group(FG).Eleven male Wistar rats were used as normal glucose controls(NG).The fluctuating high blood glucose animal model was induced by intraperitoneal injection of insulin and glucose at different time for six weeks.Intraperitoneal injection glucose tolerance test and insulin release test were performed.The area under curve of glucose(AUCg).the area under carve of insulin(AUCi)/AUCg and the ratio of insulin increment to blood glucose increment 15 min after glucose load(Δ115'/ΔG15')were calculated routinely.Then the pancreatic slides were stained with insulin antibody.The apoptotic β cells in islets were detected and quantified by the TUNEL technique.Results(1)The fasting plasma glucose and 15,30,60,and 120 min plasma glucose levels after glucose loading in FG group were significantly higher than those in control group(all P<0.01),and AUCg was also markedly increased[(1 012.14±82.62 vs 813.60±56.70)ng·ml~(-1)·h~(-1)·10~4,P<0.01].Insulin levels of FG group at 15,30,60,and 120 rain after glucose loading were significantly lower than those in HG group[(0.554± 0.18 vs 0.95±0.28.0.43±0.17 vs 0.85±0.21,0.47±0.11 vs 0.76±0.16,0.58±0.13 vs 1.08±0.26)ng/ml,P<0.05],along with decreased AUCi/AUCg and Δ115'/ΔG15'[(9.56±2.53 vs 21.36±4.16)×10~(-7);(3.95±3.45 vs 27.02±8.62)×10~(-7),both P<0.05].(2)Image analysis of pancreatic islet immunocytoehemistry showed that the insulin staining positive area,area ratio and total density of insulin positive cells per islet were significantly lower in FG group than those in HG group(P<0.05).(3)The percentage of β-cell apoptosis in the FG group was statistically higher than that in the HG group[(24.17±7.25 vs 16.55±5.11)%,P<0.01].Conclusion Compared with the consistent high blood glucose,intermittent high glucose could lead to further impairment of β-cell function and increased β-cell apoptosis may partially contribute to this process.
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Six thousand and forty-four subjects in Jiangsu community were enrolled to investigate the relationship between subclinical thyroid dysfunction and blood pressure. It was shown that subclinical thyroid dysfunction, including both the subclinical hyperthyroidism and subclinical hypothyroidism, had no relationship with increased blood pressure.
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Objective To compare the effects of rat proinsulin gene therapy via intraportal infusion and intramuscular injection blood glucose level in streptozotocin-induced diabetic rots. Methods (1) Recombinant eukaryotic cell expression plasmid of rat proinsulin gene pCMV/proiusulin was transferred into streptozotocin-induced diabetic rats by intraportal infusion and intramuscular injection to observe the effect of rat proiusulin gene therapy in diabetic rats. The treatment group by intraportal infusion (group A) and the group by intramuscular injection (group C) were given pCMV/proinsulin naked plasmid DNA 100 μg, while the control groups by intraportal infusion (group B) or by intramuscular injection (group D) were treated with similar amount of pCMV DNA. Normal group and diabetes mellitus group were also observed at the same time. (2) Blood glucose level was tested and serum insulin was determined by radioimmunoassay. RT-PCR and immunohistochemistry were used to detemine proinsulin mRNA and protein expressions in liver and skeletal muscle and protein. Results (1) The blood glucose levels in two treated groups were both decreased. In group A, levels of blood sugar decreased about 7 mmol/L and glycemie control was maintained for 3-4 weeks. Serum insulin levels step up significantly after pCMV/proinsulin gene therapy. The blood glucose level in group A was significantly lower than those of group B and DM group (P<0.05), while the serum insulin level was higher than those of two groups (P<0.05). In group C, blood glucose levels decreased about 4 mmol/L and glycemic control was maintained for 1-2 weeks. Meanwhile, the concentrations of insulin increased markedly after gene therapy. The blood glucose in group C was significantly lower than those of group D and DM group (P<0.05), while the serum insulin level was higher than those of two groups (P<0.05). (2) Proinsulin mRNA and protein expressions could be detected in either hepatic cell of group A or skeletal muscle cell of group C, not in group B and group D. Conclusion Proiusulin genetherapy via intraportal infusion or intramuscular injection lowers significantly blood glucose in diabetic rats, and thus offers a potential approach to treatment of diabetes.
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The intrauterine growth retardation (IUGR) model was established by maternal nutrition restriction during mid- to late-gestation. IUGR rats had both impaired pancreatic development and islet β-cell dysfunction. As the animals grew, the rats gradually showed impaired glucose tolerance and decreased insulin sensitivity.
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Glycemic excursion was induced in SD rats by intraperitoneal injection of 50% glucose solution, and cells isolated from bone marrow of these rats showed cell clusters which expressed insulin, c-peptide, glucagon, somatostatin and islet amyloid polypeptide, and other genes related to islet-cells development and functions.
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Objective To investigate the prevalence and epidemiologic characteristics of hypothyroidism among community population in Jiangsu province. Methods The residents who had lived for at least five years and aged more than 20 years old were sampled from six layers in urban and rural districts of Jiangsu province by a stratified cluster sampling technique. Serum was sampled from 7 122 subjects and sTSH was measured by chemiluminescence immunoassay, and FT3 and FT4 were determined in the subjects with abnormal sTSH level. Results (1) The crude prevalences of overt hypothyroidism and subclinical hypothyroidism were 0.66% and 7.53% respectively in total population, with the respective standardized rates of 0.43% and 6.28%. (2)The prevalences of hypothyroidism and subclinical hypothyroidism were significantly higher in females than in males (both P <0.05). (3) The prevalence of subclinical hypothyroidism was significantly increased with advancing age in both female and males (P<0.05). Conclusion Comparing with hypothyroidism, subclinical hypothyroidism shows higher prevalence in Jiangsu province, and more attention should be paid to the follow-up and diagnosis of subclinical hypothyroidism.
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The potential effect of donor CD4+ CD25+ regulatory T ceLls on the suppression of rejection for allogenetic islet transplantation in vivo was investigated. CD4+ CD25+ regulatory T cells were generated by magnetic activated cell sorting and were ailogeneically transfered with islet transplantation in streptozotocin-induced diabetic BALB/cByJ mice. The results showed that allogeneic CD4+ CD25+ regulatory T cells prolong islet graft survival and normoglycemia in transplanted allogeneic diabetic mice.
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Genechip was applied to explore gene expression profile of islets in rats at various stages of pregnancy. Compared with the normal control group, differential expressions of hundreds of genes were detected during pregnancy. Reg3α gene expression was markedly increased during pregnancy, which may be related to islet regeneration.
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Nicotinamide and Exendin-4 could promote transdifferentiation of rat BM-MSCs into insulin-producing cells in vitro, which expressed insulin, C-peptide and related genes.