This study is to evaluate the effects of the metformin (Met) on β cell function of diabetic KKAy mice. Female diabetic KKAy mice selected by insulin tolerance test (ITT) were divided randomly into two groups. Con group was orally administered by gavage with water, Met group with metformin hydrochloride at a dose of 0.2 g x kg(-1) for about 12 weeks. ITT and glucose tolerance tests (OGTT) were determined. Beta cell function was assessed by hyperglycemic clamp. Pancreatic biochemical indicators were tested. The changes of gene and protein expression in the pancreas and islets were also analyzed by Real-Time-PCR and immunostaining. Met significantly improved glucose intolerance and insulin resistance in KKAy mice. Fasting plasma glucose and insulin levels were also decreased. In addition, Met markedly increased glucose infusion rate (GIR) and elevated the Ist phase and maximum insulin secretion during clamp. It showed that Met decreased TG content and iNOS activities and increased Ca(2+) -Mg(2+)-ATPase activity in pancreas. Islets periphery was improved, and down-regulation of glucagon and up-regulated insulin protein expressions were found after Met treatment. Pancreatic mRNA expressions of inflammation factors including TLR4, NF-κB, JNK, IL-6 and TNF-α were down-regulated, p-NF-κB p65 protein levels also down-regulated by Met. And mRNA expressions of ion homeostasis involved in insulin secretion including SERCA2 and Kir6.2 were up-regulated by Met. Met increased SIRT5 expression level in pancreas of KKAy mice under the hyperglycemic clamp. These results indicated that chronic administration of Met regulated pancreatic inflammation generation, ion and hormone homeostasis and improved β cell function of diabetic KKAy mice.
Animals ; Blood Glucose ; Diabetes Mellitus, Experimental ; drug therapy ; Down-Regulation ; Female ; Glucose Tolerance Test ; Homeostasis ; Inflammation ; drug therapy ; Insulin ; secretion ; Insulin Resistance ; Insulin-Secreting Cells ; drug effects ; Interleukin-6 ; metabolism ; Metformin ; pharmacology ; Mice ; NF-kappa B ; metabolism ; Pancreas ; drug effects ; Tumor Necrosis Factor-alpha ; metabolism

OBJECTIVETo study the effect of Mudan Granule (MD) on the glucose metabolism and beta cell function in monosodium glutamate (MSG) induced obese mice with insulin resistance (IR).

METHODSMSG obese mice were induced by subcutaneous injecting MSG (4 g/kg for 7 successive days in neonatal ICR mice). Forty MSG mice with IR features were recruited and divided into four groups according to body weight, fasting blood glucose, triglyceride (TG), total cholesterol (TC), and the percentage of blood glucose decreased within 40 min in the IR test, i.e., the model group (Con), the low dose MD group, the high dose MD group, and the Metformin group (Met). Besides, another 10 ICR mice were recruited as the normal control group (Nor). The water solvent of 2.5 g/kg MD or 5 g/kg MD was respectively administered to mice in the low dose MD group and the high dose MD group. Metformin hydrochloride was given to mice in the Met group at 0.2 g/kg body weight. Equal dose solvent distilled water was administered to mice in the Nor group and the Con group by gastrogavage, once per day. All medication was lasted for 15 weeks. Insulin tolerance test (ITT) and oral glucose tolerance test (OGTT) were performed after 6 weeks of treatment. Beta cell function was assessed by hyperglycemic clamp technique. The morphological changes in the pancreas were evaluated by hematoxylin-eosin (HE) staining. Changes of iNOS, NF-kappaB p65, and p-NF-kappaB p65 in the pancreas were tested.

RESULTSCompared with the Nor group, the blood glucose level, AUC, and fasting blood insulin, ONOO-contents, iNOS activities, and the expression of iNOS, NF-kappaB p65 subunit, pNF-kappaB p65 subunit obviously increased; decreased percentage of blood glucose within 40 min in ITT, glucose infusion rate (GIR), Clamp 1 min insulin, and Max-Insulin obviously decreased in the Con group (P < 0.05, P < 0.01). Compared with the Con group, the aforesaid indices could be improved in the Met group (P < 0.05, P < 0.01). In the low dose MD group, AUC, iNOS activities, and the expression of iNOS and p-NF-kappaB p65 subunit obviously decreased; percentage of blood glucose within 40 min in ITT and GIR obviously increased (P < 0.05, P < 0.01). In the high dose MD group, AUC, ONOO-contents, iNOS activities, and the expression of iNOS, NF-kappaB p65 subunit, and p-NF-KB p65 subunit obviously decreased; percentage of blood glucose within 40 min in ITT, Max-Insulin, and GIR obviously increased (P < 0.05, P < 0.01).

CONCLUSIONMD could significantly improve IR and functional disorder of 3 cells in MSG obese mice, which might be associated with lowering inflammatory reaction in the pancreas.

Animals ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; Female ; Insulin Resistance ; Insulin-Secreting Cells ; drug effects ; metabolism ; Male ; Metformin ; pharmacology ; Mice ; Mice, Inbred ICR ; Mice, Obese ; Obesity ; chemically induced ; metabolism ; Pancreas ; cytology ; drug effects ; Sodium Glutamate

Human T cell leukemia virus type 1 (HTLV-1), an etiological factor that causes adult T cell leukemia and lymphoma (ATL), infects over 20 million people worldwide. About 1 million of HTLV-1-infected patients develop ATL, a highly aggressive non-Hodgkin's lymphoma without an effective therapy. The pX region of the HTLV-1 viral genome encodes an oncogenic protein, Tax, which plays a central role in transforming CD4+ T lymphocytes by deregulating oncogenic signaling pathways and promoting cell cycle progression. Expression of Tax following viral entry is critical for promoting survival and proliferation of human T cells and is required for initiation of oncogenesis. Tax exhibits diverse functions in host cells, and this oncoprotein primarily targets IκB kinase complex in the cytoplasm, resulting in persistent activation of NF-κB and upregulation of its responsive gene expressions that are crucial for T cell survival and cell cycle progression. We here review recent advances for the pathological roles of Tax in modulating IκB kinase activity. We also discuss our recent observation that Tax connects the IκB kinase complex to autophagy pathways. Understanding Tax-mediated pathogenesis will provide insights into development of new therapeutics in controlling HTLV-1-associated diseases.
Autophagy ; CD4-Positive T-Lymphocytes ; metabolism ; virology ; Cell Cycle ; Cell Transformation, Neoplastic ; genetics ; Gene Expression Regulation, Neoplastic ; Gene Products, tax ; genetics ; metabolism ; Human T-lymphotropic virus 1 ; physiology ; Humans ; I-kappa B Kinase ; genetics ; metabolism ; Leukemia-Lymphoma, Adult T-Cell ; genetics ; metabolism ; virology ; Membrane Microdomains ; metabolism ; virology ; NF-kappa B ; genetics ; metabolism ; Protein Binding ; Signal Transduction ; genetics

Objective:To evaluate the feasibility and the application values of quantitative susceptibility mapping (QSM) for the assessment of meniscal injury and in distinguishing meniscus degeneration and tears.Methods:The clinical and imaging data of 70 patients suspected of meniscus injury and scheduled for arthroscopy in Shandong Medical Imaging Research Institute, Cheeloo College of Medicine, Shandong University from November 2019 to June 2020 were analyzed retrospectively. Thirty age-and sex-matched healthy subjects were also examined as controls. All subjects received knee joint QSM and routine MR imaging. According to the results of arthroscopy, the patients was divided into meniscus degeneration and meniscus tear groups, respectively. The conventional MR was evaluated by two radiologists. The meniscus injury area was delineated on the original QSM magnitude images (the central area of the posterior corner of the lateral meniscus was selected in the healthy controls) and mapped to the corresponding QSM maps, and the magnetic susceptibility values were measured. Kruskal-Wallis H test was used to analyze the magnetic sensitivity values of meniscal degeneration, meniscal tear and healthy control groups; and Bonferroni was used to correct the pairwise comparison. ROC curve was established to evaluate the threshold and efficacy of magnetic susceptibility value in the diagnosis of meniscal tear. The results were compared with those of conventional MRI. Results:The magnetic susceptibility values of meniscus of healthy controls, meniscal degeneration and meniscal tear groups were (0.035±0.016)ppm, -0.031(-0.040,-0.005)ppm, and(-0.122±0.115)ppm, respectively, with significant difference found among the three groups (χ2=44.419, P<0.05). The magnetic susceptibility values of meniscus of healthy controls was significantly higher than those of meniscus degeneration patients and meniscus tear patients (χ2=-23.843, -48.253, P<0.05). The magnetic susceptibility values of meniscus of meniscus tear group was significant lower than those of meniscus degeneration group (χ2=-24.410, P<0.05). Taking magnetic susceptibility values of -0.062 5 ppm as threshold, the area under the ROC curve for the diagnosis of meniscal tears was 0.949, with the sensitivity as 87% and the specificity as 100%. The sensitivity and specificity of conventional MRI in the diagnosis of meniscal tears were 86.8% and 87.5%, respectively. Conclusion:QSM can quantitatively evaluate meniscus injury and can be used as an effective supplement method to conventional MRI, which is helpful to improve the diagnosis of meniscus tear.

BACKGROUNDProteasome subunits (PSMB) and transporter associated with antigen processing (TAP) loci are located in the human leukocyte antigen (HLA) Class II region play important roles in immune response and protein degradation in neurodegenerative diseases. This study aimed to explore the association between single nucleotide polymorphisms (SNPs) of PSMB and TAP and Parkinson's disease (PD).

METHODSA case-control study was conducted by genotyping SNPs in PSMB8, PSMB9, TAP1, and TAP2 genes in the Chinese population. Subjects included 542 sporadic patients with PD and 674 healthy controls. Nine identified SNPs in PSMB8, PSMB9, TAP1, and TAP2 were genotyped through SNaPshot testing.

RESULTSThe stratified analysis of rs17587 was specially performed on gender. Data revealed that female patients carry a higher frequency of rs17587-G/G versus (A/A + G/A) compared with controls. But there was no significant difference with respect to the genotypic frequencies of the SNPs in PSMB8, TAP1, and TAP2 loci in PD patients.

CONCLUSIONChinese females carrying the rs17587-G/G genotype in PSMB9 may increase a higher risk for PD, but no linkage was found between other SNPs in HLA Class II region and PD.

ATP-Binding Cassette Sub-Family B Member 2 ; genetics ; ATP-Binding Cassette, Sub-Family B, Member 3 ; genetics ; Adult ; Aged ; Antigen Presentation ; Case-Control Studies ; Cysteine Endopeptidases ; genetics ; Female ; Humans ; Male ; Middle Aged ; Parkinson Disease ; genetics ; immunology ; Polymorphism, Single Nucleotide ; Proteasome Endopeptidase Complex ; genetics

BACKGROUNDTreatment for malignant glioma generally consists of cytoreductive surgery followed by radiotherapy and chemotherapy. In this study, we intended to investigate the effects of 2-propylpentanoic acid (VPA), a histone deacetylase inhibitor, on chemosensitivity and radiosensitivity in human glioma cell lines.

METHODSHuman glioma cell lines, T98-G, and SF295, were treated with temozolomide (TMZ) or irradiation (IR), with or without VPA (1.0 mmol/L). Then, cytotoxicity and clonogenic survival assay was performed. Cell cycle stage, apoptosis, and autophagy were also detected using flow cytometry and dansyl monocadaverin (MDC) incorporation assay. One-way analysis of variance (ANOVA) and t-test were used to analyze the differences among variant groups.

RESULTSMild cytotoxicity of VPA was revealed in both cell lines, T98-G and SF295, with the 50% inhibiting concentration (IC50) value of (3.85 ± 0.58) mmol/L and (2.15 ± 0.38) mmol/L, respectively; while the IC50 value of TMZ was (0.20 ± 0.09) mmol/L for T98-G and (0.08 ± 0.02) mmol/L for SF295. Moreover, if combined with VPA (1.0 mmol/L) for 96 hours, the sensitivity of glioma cells to TMZ was significant increased (P < 0.05). The surviving fractions at 2 Gy (SF2) of T98-G and SF295 cells exposed to IR alone were 0.52 and 0.58. However, when VPA was combined with IR, the SF2 of T98-G and SF295 dropped to 0.39 (P = 0.047) and 0.49 (P = 0.049), respectively. Treatment with VPA plus TMZ or IR also resulted in a significant decrease in the proportion of cells in the G2 phase and increased apoptotic rates as well as autophagy in T98-G and SF295 cell lines (P < 0.01).

CONCLUSIONVPA may enhance the activities of TMZ and IR on glioma cells possibly through cell cycle block and promote autophagy, and thus could be a potential sensitizer of glioma treatment.

Apoptosis ; drug effects ; radiation effects ; Blotting, Western ; Cell Line, Tumor ; Cell Survival ; drug effects ; radiation effects ; Dacarbazine ; analogs & derivatives ; pharmacology ; Flow Cytometry ; Glioma ; metabolism ; Histone Deacetylase Inhibitors ; pharmacology ; Humans ; Valproic Acid ; pharmacology

Objective To observe the brain activation of interictal epiletiform discharges(IEDs) and to localize the epileptogenic foci of epilepsy.Methods The electroencephalogram(EEG)and functional MRI data of 12 focal epileptic patients were acquired using a combination of EEG and functional MRI simultaneously.The IEDs onset time detected with EEG were set as the time parameters in an event- related paradigm of functional MRI analysis.The spatial and temporal characters of IEDs activation were analyzed in detail.In order to confirm the consistency of this method,all patients were scanned repeatedly and the results were correlated with clinical evaluation.Results Of the 12 patients,valid data from EEG- fMRI were obtained from 10 patients in a total of 18 sessions..Compared with the structural foci,the epileptic foci localization results of eleven sessions were good,five sessions were fairly good,and two sessions were poor.The results obtained from six patients in two separate sessions were concordant.respectively.Moreover,thalamic activation was detected in ten sessions,cerebellar activation was detected in all sessions,and the deactivation was found in the default mode loci in nine sessions. Conclusion The method of performing EEG and fMRI simultaneously can potentially be a useful tool in epilepsy research.

Objective To evaluate the relationship between the hepatic toxicity induced by chemotherapy in patients with malignant tumor who test positive for HBV markers. Methods From January 2008 to January 2014, 887 cancer patients were treated by chemotherapy. Among 274 cases of patients were HBV positive (positive group), 613 patients were HBV negative (negative group), the liver function after chemotherapy were compared. Results Positive group patients receiving chemotherapy had higher rate of hepatic toxicity than those in negative group (24.1% vs. 11.3%,P<0.01),the incidence rate of 3-4 grade hepatic toxicity in positive group patients was 11.2%(13/116),more than that in negative group 0.65%(4/613). In the different treatment, there were statistically significant in two groups by TP regimen(paclitaxel+cisplatin), CAF(cyclophosphamide+adriamycin+5-Fluorouracil), CHOP(cyclophosphamide+doxorubicin+oncovin+prednisone)liver function after chemotherapy (P<0.05). In the TP scheme leaded to the incidence of abnor-mal liver function was the highest, the incidence rate in positive group was 36%(18/50),the incidence rate in negative group was 15.8%(19/120). Conclusion HBV infection is associated with higher risk of hepatic toxicity in patients with malignant tumor during chemotherapy(led by TP scheme).

OBJECTIVETo evaluate visual inspection with Lugol's iodine (VILI) in cervical cancer screening program and to provide evidence for designing a cervical cancer screening algorithm in high risk areas of existing low-resource settings to reduce the incidence and mortality of cervical cancer.

METHODSWomen in Yangcheng county, Shanxi province were screened with VILI, colposcopy, liquid-based cytology test and human papilloma virus (HPV) DNA test. The efficacy of different screening tests was compared by Youden's index based on the pathology as the gold standard.

RESULTSIn the population being screened, the mean age was 40.80 +/- 10.75 years old. Based on pathological findings, 4.35% (32/735) of the subjects had >or= CIN (cervical intraepithelial neoplasia) II. The sensitivity and specificity for the VILI test (>or= positive) were 53.13 and 82.19, while 56.25 and 79.09 were for colposcopy (>or= low grade dysplasia) respectively. Comparing by the Youden's indexs, there was no statistically significant difference (P > 0.05) between VILI and colposcopy. However, statistical significant difference (P < 0.05) was found between VILI and liquid-based cytology test and HPV DNA test. In addition, there was no statistically significant difference (P > 0.05) found between the experienced doctors and the newly-trained doctors working in the field station.

CONCLUSIONWith low sensitivity when using microscope but low cost of equipments, VILI can be one of the primary screening tests in China's rural area with low-resource settings if the screening frequency is to be increased.

Adult ; Cervical Intraepithelial Neoplasia ; diagnosis ; epidemiology ; China ; epidemiology ; Early Detection of Cancer ; economics ; methods ; Female ; Health Resources ; Humans ; Incidence ; Iodides ; Program Evaluation ; Rural Health ; Sensitivity and Specificity ; Socioeconomic Factors ; Uterine Cervical Neoplasms ; diagnosis ; epidemiology

OBJECTIVETo analyze the capacity of personal protection on poison emergency items in Chinese disease control and prevention institutes.

METHODSEvaluation analysis based on data obtained from investigating personal protection equipments and professional knowledge quizzing about personal protection in poisoning control of 57 different level centers for disease control and prevention selected from China by a multi-stage stratified sampling.

RESULTSAll 80.70% of the institutes possessed the protection equipments, provincial, municipal, county level institutes were 100.00%, 95.24%, 66.67%, respectively, with significant statistical difference (H = 7.94, P < 0.05). The average level of the type of individual protective equipments in disease control and prevention institutes was (5.42 +/- 4.00) kinds, the average points in category of provincial, municipal, county level institutes were (11.33 +/- 3.67), (6.52 +/- 3.16), (3.47 +/- 3.10) kinds, being statistically significant (F = 17.30, P < 0.05); type difference counts of disease control and prevention institutes in economic development, secondary, less-developed regions were (6.41 +/- 4.03), (3.55 +/- 3.35), (6.45 +/- 4.07) kinds, with statistical significance (F = 3.70, P < 0.05). Protection equipments chiefly possessed were latex gloves, gauze masks and C-protective clothing. Protective clothing and respiratory protective equipments were insufficient evidently. The average points in testing personal protection basic knowledge were (71.39 +/- 12.52) points; there were no differences between different institutes with different economic regions, levels, technical posts and title degrees.

CONCLUSIONCertain advances have been achieved in recent years in personal protection capacity of institutes for disease control and prevention, but far from the actual demands, and maybe no enough effective response on emergency occurred.

China ; Emergencies ; Humans ; Occupational Exposure ; Poisoning ; prevention & control ; Protective Clothing