Clinical efficacy of first-line immunotherapy plus anti-angiogenesis targeted therapy in the treatment of advanced hepatocellular carcinoma / 中华消化外科杂志

Hepatocellular carcinoma has a high morbidity and mortality, which has seriously harmed human health. Several targeted therapies have been approved for the first- and second-line treatment of advanced hepatocellular carcinoma. The emergence of immunotherapy has brought the treatment of hepatocellular carcinoma into a new era. Targeted and immunotherapeutic agents have synergistic effects in mechanism, also the combination of these two therapies has been clinically beneficial to patients with advanced hepatocellular carcinoma. At the same time, in addition to the systemic therapy of targeted combined immunological, applying appropriate local therapy can provide a longer survival period or even a chance of cure for that some patients. The authors introduce the diagnosis and treatment of a case of advanced hepatocellular carcinoma who achieved pathological complete remission by first-line immunotherapy combined with anti-angiogenesis targeted therapy.

The use of miR122 and its target sequence in adeno-associated virus-mediated trichosanthin gene therapy / 中西医结合学报

OBJECTIVE@#Plant-derived cytotoxic transgene expression, such as trichosanthin (tcs), regulated by recombinant adeno-associated virus (rAAV) vector is a promising cancer gene therapy. However, the cytotoxic transgene can hamper the vector production in the rAAV producer cell line, human embryonic kidney (HEK293) cells. Here, we explored microRNA-122 (miR122) and its target sequence to limit the expression of the cytotoxic gene in the rAAV producer cells.@*METHODS@#A miR122 target (122T) sequence was incorporated into the 3' untranslated region of the tcs cDNA sequence. The firefly luciferase (fluc) transgene was used as an appropriate control. Cell line HEK293-mir122 was generated by the lentiviral vector-mediated genome integration of the mir122 gene in parental HEK293 cells. The effects of miR122 overexpression on cell growth, transgene expression, and rAAV production were determined.@*RESULTS@#The presence of 122T sequence significantly reduced transgene expression in the miR122-enriched Huh7 cell line (in vitro), fresh human hepatocytes (ex vivo), and mouse liver (in vivo). Also, the normal liver physiology was unaffected by delivery of 122T sequence by rAAV vectors. Compared with the parental cells, the miR122-overexpressing HEK293-mir122 cell line showed similar cell growth rate and expression of transgene without 122T, as well as the ability to produce liver-targeting rAAV vectors. Fascinatingly, the yield of rAAV vectors carrying the tcs-122T gene was increased by 77.7-fold in HEK293-mir122 cells. Moreover, the tcs-122T-containing rAAV vectors significantly reduced the proliferation of hepatocellular carcinoma cells without affecting the normal liver cells.@*CONCLUSION@#HEK293-mir122 cells along with the 122T sequence provide a potential tool to attenuate the cytotoxic transgene expression, such as tcs, during rAAV vector production.

Demethylzeylasteral (T-96) initiates extrinsic apoptosis against prostate cancer cells by inducing ROS-mediated ER stress and suppressing autophagic flux

BACKGROUND: Demethylzeylasteral (T-96) is a pharmacologically active triterpenoid monomer extracted from Tripterygium wilfordii Hook F (TWHF) that has been reported to exhibit anti-neoplastic effects against several types of cancer cells. However, the potential anti-tumour effects of T-96 against human Prostate cancer (CaP) cells and the possible underlying mechanisms have not been well studied. RESULTS: In the current study, T-96 exerted significant cytotoxicity to CaP cells in vitro and induced cell cycle arrest at S-phase in a dose-dependent manner. Mechanistically, T-96 promoted the initiation of autophagy but inhibited autophagic flux by inducing ROS-mediated endoplasmic reticulum (ER) stress which subsequently activated the extrinsic apoptosis pathway in CaP cells. These findings implied that T-96-induced ER stress activated the caspase-dependent apoptosis pathway to inhibit proliferation of CaP cells. Moreover, we observed that T-96 enhances the sensitivity of CaP cells to the chemotherapeutic drug, cisplatin. CONCLUSIONS: Taken together, our data demonstrated that T-96 is a novel modulator of ER stress and autophagy, and has potential therapeutic applications against CaP in the clinic.

Functional relationship between photosynthetic leaf gas exchange in response to silicon application and water stress mitigation in sugarcane

BACKGROUND: Water stress is one of the serious abiotic stresses that negatively influences the growth, development and production of sugarcane in arid and semi-arid regions. However, silicon (Si) has been applied as an alleviation strategy subjected to environmental stresses. METHODS: In this experiment, Si was applied as soil irrigation in sugarcane plants to understand the mitigation effect of Si against harmful impact of water stress on photosynthetic leaf gas exchange. RESULTS: In the present study we primarily revealed the consequences of low soil moisture content, which affect overall plant performance of sugarcane significantly. Silicon application reduced the adverse effects of water stress by improving the net photosynthetic assimilation rate (Anet) 1.35-18.75%, stomatal conductance to water vapour (gs) 3.26-21.57% and rate of transpiration (E) 1.16-17.83%. The mathematical models developed from the proposed hypothesis explained the functional relationships between photosynthetic responses of Si application and water stress mitigation. CONCLUSIONS: Silicon application showed high ameliorative effects on photosynthetic responses of sugarcane to water stress and could be used for mitigating environmental stresses in other crops, too, in future.

Optimized experimental method for determination of hydroxyproline in lung tissue of mice / 医学研究生学报

ObjectiveThere are many methods for the detection of hydroxyproline (HYP), but few of them are suitable for the detection of lung tissue in mice. We intend to establish an accurate and reliable method for measuring HYP levels based on mouse lung tissues to assess the degree of fibrosis development more effectively.MethodsBased on the alkali hydrolysis method, the effects of the concentration of alkali hydrolysate and hydrolysis time on the determination results of HYP level in mice lung tissue were compared; the effects of the changes of experimental conditions on the determination results of HYP standard were compared; and the results of the determination of HYP level in mice lung tissue under dry and wet conditions were compared on the basis of the above experimental results.ResultsThe optimum concentration of alkali hydrolysate is 2 mol/L and the optimum hydrolysis time is 20 min. The optimum pH value of citric acid buffer is 6.0-6.5. The optimum solvent for chloramine T is methanol, the optimum reaction time for chloramine T solution is 15 min, the optimum reaction time for perchloric acid solution is 5 min, and the optimum reaction time for 4-(dimethylamino) benzoyl toluene is 5 min. The optimum condition of aldehyde solution color development is that it is bathed in water at 85 for 3 minutes. Some related reagents are stored in suitable environment after preparation, and the experimental data will not be affected within 7 days. Dry lung tissue of mice can improve the detection level of HYP. The improved experimental protocol was applied to the bleomycin-induced mouse pulmonary fibrosis model, and the HYP measurement results were significantly higher than that of the original protocol.ConclusionAn accurate and reliable method for the determination of hydroxyproline in lung tissue of mice was established.

Detection of donor kidney carrier carbapenem-resistant Klebsiella pneumoniae using combined GeneXpert and culture of kidney perfusion fluid / 中华器官移植杂志

Objective:To explorer the optimal method of detecting donor kidney carrier carbapenem-resistant Klebsiella pneumoniae (CRKP).Methods:Clinical data were retrospectively analyzed for 1120 donation-after-circulatory-death (DCD) kidneys and bacterial detection of kidney perfusion fluid was performed from January 2015 to January 2019. A total of 1120 kidney perfusion fluid samples were collected with sterile tubes and submitted for culturing. And 451 specimens were delivered in sterile tubes and blood culture bottles simultaneously And 729 specimens assayed for carbapenemase genes with GeneXpert.Results:Among 1120 kidneys, CRKP was confirmed in 21 grafts with an infection rate of 1.87 %. The detection of carbapenemase genes with Genexpert showed that KPC was positive for 9/16 CRKP positive grafts. Sensitivity, specificity, false-positive rate, false-negative rate and ROC-AUC were calculated at 56.3 %, 100 %, 0, 43.7 % and 0.781 respectively. And 11 specimens delivered with sterile tube were culture positive for CRKP. Sensitivity, specificity, false-positive rate, false-negative rate and ROC-AUC were calculated at 52.3 %, 100 %, 0, 47.6 % and 0.762 respectively. Among 451 perfusion fluid samples collected with anaerobic blood culture bottle, 15 samples had a positive culture for CRKP. Sensitivity, specificity, false-positive rate, false-negative rate and ROC-AUC were calculated at 100 %, 100 %, 0, 0 and 1 respectively. In terms to anaerobic blood culture bottle, sensitivity, specificity, false-positive rate, false-negative rate and ROC-AUC were calculated at 60 %, 100 %, 0 , 40 % and 0.80 respectively.Conclusions:Genexpert assay is suitable for rapid and convenient detection of carbapenemase genes using kidney perfusion fluid. Culturing perfusion fluid samples collected with anaerobic blood culture bottle is clinically valuable diagnostic tool of CRKP. A combination of both methods is worthy of clinical promotion and application diagnosis of donor kidney derived CRKP in terms of greater accuracy and timeliness.

Expression of MiR-429 in Patients with Acute Lymphoblastic Leukemia and Its Prognostic Value / 中国实验血液学杂志

OBJECTIVE@#To analyze the expression level of miR-429 in patients with acute lymphoblastic leukemia(ALL) and its clinical prognostic value.@*METHODS@#One hundred and Twenty-six patients with ALL treated in our hospital from April 2016 to February 2018 were selected, and 100 healthy persons in the same period were selected as control group. Bone marrow mononuclear cells were collected. The expression level of miR-429 in bone marrow mononuclear cells was detected by RT-PCR, and the correlation of miR-429 expression with clinical characteristics and therapeutic efficacy was analyzed. Kaplan-Meier method and multi-factorial Cox regression model were used to analyze the correlation between the level of microRNA-429 and the prognosis of ALL patients.@*RESULTS@#The relative level of miR-429 in ALL patients was 2.47±0.07, which was signifi-cantly higher than that in control group (P0.05). The level of miR-429 was not significantly different between CR patients and control group (P>0.05); the level of miR-429 in PR patients was higher than that in control group and CR patients (P<0.05). The level of miR-429 in NR patients was higher than that in other groups (P<0.05). Kaplan-Meier survival analysis showed that the overall survival rate of ALL patients with low expression of miR-429 was better than that of ALL patients with high expression of miR-429 (P<0.05). Univariate Cox regression analysis showed that leukocyte level, ratio of bone marrow primordial cells, Hb and LDH level, risk grading and miR-429 were the factors influencing overall survival rate in ALL patients (P<0.05). Multivariate Cox regression analysis showed that leukocyte level, ratio of bone marrow primordial cells, risk grading, and miR-429 were the factors influencing overall survival rate (P<0.05).@*CONCLUSION@#The expression of miR-429 is high in ALL patients, which closely relates to the curative effect and pro-gnosis of ALL patients, and can be used as a reference index for evaluation of clinical prognosis of ALL patients.

Diagnosis and treatment in 9 cases of donor-derivedcarbapenem-resistant Klebsiella pneumoniae Infection after kidney transplantation / 中华器官移植杂志

Objective To explore the rapid diagnosis and clinic treatment of donor-derived carbapenem-resistant Klebsiella pneumoniae (CRKP) infection in renal transplant recipients .Methods Retrospective analysis was performed for clinical data and the diagnosis and treatment of 9 renal transplant recipients with donor-derived CRKP infection from March 2017 to May 2019 .Results Among 526 renal transplant recipients ,nine were diagnosed with donor-derived CRKP infection by bacterial culture or KPC enzyme gene test .The infection rate was 1 .71％ .One recipient receiving carbapenem and tigecycline died while the remainders survived after a treatment of ceftazidime-avibactam and carbapenem . One recipient underwent graft resection . Among 8 recipients on ceftazidime-avibactam ,5 cases received a standard dose of 3 .75 g/d while another 3 cases had a high dose of 7 .5 g/d .One patient in standard-dose group underwent graft resection due to an arteriorrhexis of artery anastomosis .After graft resection ,the patient received a high dose of ceftazidime-avibactam and survived to date .The grafts of three patients in high-dose treatment group survived .Conclusions KPC enzyme gene detection plus injecting lavage fluid into blood culture bottle for bacterial culture is rapid and accurate for diagnosing donor-derived CRKP infection . A combination of ceftazidime-avibactam plus carbapenem is effective for donor-derived CRKP infection .A high dose of ceftazidime-avibactam may improve the efficacy without obvious side effects .

Identification of Matrix Metalloproteinase-2 and 9 as Biomarker of Intrahepatic Cholestasis of Pregnancy

ABSTRACT Intrahepatic cholestasis of pregnancy (ICP) is a severe liver disease uniquely occurring during pregnancy. In this study we aimed to identify novel biomarker for the diagnosis of ICP in Chinese population. 50 healthy pregnant women, 50 mild ICP patients and 48 severe ICP patients were enrolled for this study. Liver function tests, including serum total bilirubin, direct bilirubin, alanine transaminase, aspartate aminotransferase and cholyglycine, were performed in all participants. After an overnight fast serum levels of total bile acids (TBA), matrix metalloproteinase (MMP)-2 and MMP-9 were measured, and their correlation with liver function tests were analyzed. The observed increase in serum TBA in ICP patients was not statistically significant which made it unreliable for diagnosis of ICP in Chinese population. On the other hand, both MMP-2 and MMP-9 serum levels exhibited a progressive and significant elevation in mild and severe ICP patients compared with healthy pregnant women, which also positively correlated with liver function tests. Serum levels of both MMP-2 and MMP-9 could be reliably used as laboratory abnormalities for accurate diagnosis and sensitive grading of ICP in Chinese population.

Effect of docosapentenoic acid on the neurite outgrowth in PC12 cells / 中华行为医学与脑科学杂志

ObjectiveTo explore the inductive action of docosapentenoic acid(DPA) on neurite outgrowth in PC12 cells in vitro.MethodsNeurite outgrowth in PC12 cells was examined after the treatment with different concentration of DPA using Motic Zamges Plus software mapping cell image system.Western blot was performed to detect the expression of β Ⅲ-tubulin regulated protein kinase,a neuronal marker as well as ERK and protein kinase B (Akt) phosphorylation.ResultsPC12 cell neurite formation rate was increased in a concentration dependent manner in the induction of DPA,increased by 2.4% (DPA 10 μg/ml,P>0.05),18.6% (DPA 30 μg/ml,P<0.05) and 25.0% (DPA 50 μg/ml,P<0.05) compared with that in the control group.DPA promoted the expression of β Ⅲ-tubulin (P<0.05) and the phosphorylation level of ERK and Akt (P<0.05,P<0.01).ConclusionDPA promotes PC12 cell neurites growth and its mechanism may be related to the activation of ERK and Akt signaling pathways.

Allopurinol preconditioning attenuates renal ischemia/reperfusion injury by inhibiting HMGB1 expression in a rat model

ABSTRACT PURPOSE: To investigate the potential effects of pretreatment with allopurinol on renal ischemia/reperfusion injury (IRI) in a rat model. METHODS: Twenty four rats were subjected to right kidney uninephrectomy were randomly distributed into the following three groups (n=8): Group A (sham-operated group); Group B (ischemic group) with 30 min of renal ischemia after surgery; and Group C (allopurinol + ischemia group) pretreated with allopurinol at 50 mg/kg for 14 days. At 72 h after renal reperfusion, the kidney was harvested to assess inflammation and apoptosis. RESULTS: Pretreatment with allopurinol significantly improved renal functional and histological grade scores following I/R injury (p<0.05). Compared with Group B, the expression levels of caspase-3 and Bax were markedly reduced in Group C, meanwhile, whereas expression of bcl-2 was clearly increased (p<0.05). A newly described marker of inflammation, High Mobility Group Box 1(HMGB1), showed reduced expression in Group C (p<0.05). CONCLUSION: Pretreatment with allopurinol had a protective effect on kidney ischemia/reperfusion injury, which might be related to the inhibition of HMGB1 expression.

Comparison of endothelial differentiation capacity of adipose-derived stem cells and bone marrow mesenchymal stem cells from rats / 南方医科大学学报

<p><b>OBJECTIVE</b>To compared the differentiation capacity of rat adipose-derived stem cells (ASCs) and bone marrow mesenchymal stem cells (BMSCs) into endothelial cells.</p><p><b>METHODS</b>Rat BMSCs and ASCs were isolated, cultured and identified for cell surface markers using flow cytometry. The cell growth curves were drawn by CCK-8 assay, and the cells in active growth were induced for endothelial differentiation following standard protocols. On day 21 of induction, the cells were examined for mRNA expressions of endothelial cell specific markers CD31, KDR, and vWF using qPCR. Immunostaining was performed to observe the expression of CD31 on the cells. The induced cells were also tested for Dil-labeled acetylated low-density lipoprotein (ac-LDL) uptake ability. The tube-forming ability of the induced cells was verified on Matrigel.</p><p><b>RESULTS</b>We successfully isolated rat ASCs and BMSCs. Morphologically, ASCs were similar with BMSCs, both having long spindle-shaped and fibroblast-like morphology. Flow cytometry showed that both BMSCs and ASCs had high expressions of mesenchymal markers CD29 and CD90 and a low expression of hematopoietic cell surface markers CD45. CCK-8 assay showed that ASCs proliferated more quickly than BMSCs. The cells with induced endothelial differentiation exhibited increased levels of CD31, KDR, and vWF mRNA expressions and immunofluorescent staining identified CD31 antigen expression on the cell membrane. Fluorescence microscopy revealed red fluorescence in the induced cells suggesting uptake of Dil-Ac-LDL by the cells. The induced cells were capable of forming tube on Matrigel, confirming their identity of endothelial cells.</p><p><b>CONCLUSION</b>Both rat BMSCs and ASCs can be induced to differentiate into endothelial cells, but ASCs differentiate more quickly into endothelial cells and possess a stronger proliferation ability, suggesting its greater potential than BMSCs in future applications.</p>

Small activating RNA induces myogenic differentiation of rat adipose-derived stem cells by upregulating MyoD

ABSTRACTPurpose:RNA activation (RNAa) is a mechanism of gene activation triggered by promoter-targeted small double stranded RNAs (dsRNAs), also known as small activating RNAs (saRNAs). Myogenic regulatory factor MyoD is regarded as the master activator of myogenic differentiation cascade by binding to enhancer of muscle specific genes. Stress urinary incontinence (SUI) is a condition primarily resulted from urethral sphincter deficiency. It is thus expected that by promoting differentiation of adipose-derived stem cells (ADSCs) into myoblasts by activating MyoD gene through RNAa may offer benefits to SUI.Materials and Methods:Rats ADSCs were isolated, proliferated in vitro, and identified by flow cytometry. Purified ADSCs were then transfected with a MyoD saRNA or control transfected. Real-time polymerase chain reaction (RT-PCR) and western blotting were used to detect MyoD mRNA and protein expression, respectively. Immunocytochemical staining was applied to determine the expression of desmin protein in transfected cells. Cell viability was measured by using CellTiter 96® AQueous One Solution Cell Proliferation Assay kit.Results:Transfection of a MyoD saRNA (dsMyoD) into ADSCs significantly induced the expression of MyoD at both the mRNA and protein levels, and inhibited cell proliferation. Desmin protein expression was detected in dsMyoD treated ADSCs 2 weeks later.Conclusion:Our findings show that RNAa mediated overexpression of MyoD can promote transdifferentiation of ADSCs into myoblasts and may help treat stress urinary incontinence (SUI)–a condition primarily resulted from urethral sphincter deficiency.

Expression of Neuritin and its clinical significance in gastric cancer / 重庆医学

Objective To research the expression of Neuritin in gastric cancer .and the relationship between the expression of Neuritin with the occurrence and development of gastric cancer .Methods Collected 58 surgical specimens of gastric cancer from 2010 to 2013 in the first affiliated hospital of Shihezi University ,immunohistochemistry was used to examine the expression of Neu-ritin in gastric cancer and normal tissues near the cancer of the stomach .Results Immunohistochemical staining showed that Neu-ritin was moderately or highly expressed in 96 .55% (56/58) of gastric cancer ,and Neuritin was moderately or highly expressed in 94 .83% (55/58) of normal tissues near the cancer .There was no statistically significantly difference between two groups (P>0 .05);Neuritin was highly expressed in 82 .76% (48/58) of gastric cancer ,and Neuritin was highly expressed in 15 .52% (9/58) of normal tissues near the cancer ,differences between the two groups had statistically significantly (P 0 .05) .Conclusion The Neuritin expression level between gastric cancer and normal tissues near the cancer exist differences .There is overexpression of neuritin in gastric cancer .

Design, synthesis and antitumor activity of valproic acid salicylanilide esters / 药学学报

A series of valproic acid salicylanilide esters were designed and synthesized based on the principle of prodrug. The structures of the target compounds were confirmed by MS, 1H NMR and 13C NMR. Anti-tumor activities of these compounds against K562, A549, A431 cells in vitro were investigated by MTT assay and SRB assay. The results indicated that the compounds 6h-6j were found to have stronger cell growth inhibitory action than gefitinib, and comparable to niclosamide, which are worth to be intensively studied further.

Effects of female diet and age on offspring sex ratio of the solitary parasitoid Pachycrepoideus vindemmiae (Rondani) (Hymenoptera, Pteromalidae) / Efeitos da dieta e idade da fêmea em relação à prole e à razão sexual do parasitoide solitário Pachycrepoideus vindemmiae (Rondani) (Hymenoptera, Pteromalidae)

Effects of female diet and age on offspring sex ratio of the solitary parasitoid Pachycrepoideus vindemmiae (Rondani) (Hymenoptera, Pteromalidae). Theories predict that females of parasitoid wasps would adjust the offspring sex ratio to environmental conditions in the oviposition patch, but the diet and age of females would also affect the sex ratio adjustment. Our focus was to test the effects of female diet and age on offspring sex ratio of the solitary parasitoid wasp, Pachycrepoideus vindemmiae (Rondani, 1875). Our results showed that females fed with honey had significantly less female biased offspring sex ratio than those fed only with water. Offspring sex ratio (male percentage) decreased with female age or female longevity at the beginning of oviposition but increased at the end. There should be a sperm limitation in P. vindemmiae females at the end of oviposition, and a higher frequency of unfertilized eggs were laid then. Females also laid more unfertilized eggs at the beginning of oviposition, which would be necessary to insure the mating among offspring. Male offspring developed faster and emerged earlier, which would also reduce the risk of virginity in offspring with female-biased sex ratio.

Efeitos da dieta e idade da fêmea em relação à prole e à razão sexual do parasitoide solitário Pachycrepoideus vindemmiae (Rondani) (Hymenoptera, Pteromalidae). As teorias predizem que as fêmeas parasitoides de vespas ajustam a relação razão sexual dos descendentes, de acordo com condições ambientais, em cada oviposição. Entretanto, a dieta e idade das fêmeas também podem afetar o ajuste da razão sexual. Nosso foco foi testar os efeitos da dieta e idade da fêmeas em relação a razão sexual da prole da vespa parasitoide Pachycrepoideus vindemmiae (Rondani, 1875). Nossos resultados mostraram que as fêmeas alimentadas com mel apresentaram uma razão sexual significativa menor de fêmeas, do que aquelas alimentadas apenas com água. A razão sexual (percentagem dos machos) diminuiu com a idade ou longevidade das fêmeas no início da oviposição, mas com aumento no final. Deve haver uma limitação de esperma nas fêmeas de P. vindemmiae no final da oviposição e uma maior frequência de posturas de ovos infertilizados. As fêmeas também fazem posturas de um número maior de ovos infertilizados no início da oviposição, que seria necessário para assegurar o acasalamento entre os descendentes. A prole masculina desenvolverá mais rapidamente e emergirá mais cedo, o que também reduziria o risco de virgindade da prole, com a tendenciosa proporção de razão sexual maior das fêmeas.

Synthesis of ferulic acid derivatives and their inhibitory effect on platelet aggregation / 药学学报

Ferulic acid, an useful compound of Chinese traditional medicine, was used as leading compound. Six ferulic acid derivatives were designed and synthesized based on bioisosterism. Their structures were characterized by IR, 1H NMR, 13C NMR and mass spectra. In vivo experiment showed that ferulic acid derivatives had good inhibitory effects on adenosine diphosphate (ADP) induced platelet aggregation, which were significantly higher than that of Ozagrel.

Cellular memory of high glucose exposure in normoglycemia is probably mediated by reactive oxygen species in INS-1 cells / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the cellular memory of previous high glucose exposure in rat islet cell line (INS-1) and explore the possible mechanism.</p><p><b>METHODS</b>INS-1 cells were exposed to a high glucose (33.3 mmol/L) culture for 48 h followed by further culture in the presence of 11.1 mmol/L glucose in the culture medium for 3 or 5 days. The levels of bax and caspase-3 mRNA were measured by real-time PCR, the production of reactive oxygen species (ROS) was assayed using the dihydroethidium probe, and the cell viability was detected by MTT assay.</p><p><b>RESULTS</b>High glucose exposure of the cells for 48 h resulted in significantly increased ROS production and bax and caspase-3 mRNA expressions and lowered cell viability (P<0.001). In cells cultured in 11.1 mmol/L glucose following previous high glucose exposure, the ROS production and bax and caspase-3 mRNA expressions still maintained the high levels (P<0.05) while the cell viability remained significantly lower than the control cells (P<0.001).</p><p><b>CONCLUSION</b>High glucose causes persistent changes in cell viability and apoptosis-related gene expressions even after recovery of normoglycemia, the mechanism of which is probably related to increased ROS production.</p>

Adiponectin decreases insulin receptor substrate-1 phosphorylation in the liver of OLETF rats possibly through nuclear factor-κB signaling pathway / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effect of adiponectin (APN) on the insulin pathway in the liver of OLETF rats and explore its molecular mechanism.</p><p><b>METHODS</b>Twenty male OLETF rats and 10 male LETO rats were sacrificed at 8 and 32 weeks of age to examine the fasting blood glucose, serum insulin, adiponectin and blood lipid profiles. The APN, phosphotyrosine of insulin receptor substrate-1 (IRS-1), IKKβ and nuclear-κB (NF-κB) in the liver tissue were determined using ELISA, Western blotting or immunohistochemistry.</p><p><b>RESULTS</b>The plasma adiponectin level in OLETF rats was significantly lower than that of LETO rats since 8 weeks of age (P<0.01). At 32 weeks of age, the blood lipid levels of OLETF rats increased significantly (P<0.05) with inverse correlations to plasma adiponectin (P<0.01). The liver APN, py-IRS-1, IKKβ and NF-κB levels in OLETF rats differed significantly from those of LETO rats at both 8 and 32 weeks. At 32 weeks of age, the APN level of both rats were correlated to the levels of NF-κB and py-IRS-1 (P<0.01).</p><p><b>CONCLUSION</b>APN may decrease tyrosine phosphorylation of IRS-1 via the IKK/NFκB pathway and inhibit insulin signaling pathway in the liver, which contributes to hyperlipidemia, hyperglycemia and development of type 2 diabetes.</p>

Hypoadiponectinemia leads to insulin resistance in OLETF rats: a preliminary study / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the association between plasma adiponectin and insulin resistance in OLETF rats.</p><p><b>METHODS</b>Twenty male Otsuka Long-Evans Tokushima Fatty (OLETF) rats and 10 male Long-evans Tokushima Otsuka (LETO) rats underwent oral glucose tolerance test (OGTT) at 13 and 40 weeks of age. At 8, 32 and 40 weeks of age, the rats were sacrificed to measure the blood glucose, plasma insulin and adiponectin levels, and serum levels of TG, CHOL and FFA.</p><p><b>RESULTS</b>The plasma adiponectin level was significantly decreased in 8-week-old OLETF rats compared with that of LETO rats (P<0.05). The plasma insulin level, TG, CHOL, and FFA were significantly higher in OLETF rats than in LETO rats at 32 and 40 weeks of age.</p><p><b>CONCLUSION</b>A decreased plasma level of adiponectin preludes insulin resistance and is inversely correlated to insulin sensitivity. Hypoadiponectinemia may be an important reason leading to insulin resistance.</p>