BACKGROUND Increasing data indicated that long noncoding RNAs(lncRNAs)were directly or indirectly involved in the occurrence and development of tumors,including hepatocellular carcinoma(HCC).Recent studies had found t...BACKGROUND Increasing data indicated that long noncoding RNAs(lncRNAs)were directly or indirectly involved in the occurrence and development of tumors,including hepatocellular carcinoma(HCC).Recent studies had found that the expression of lncRNA HAND2-AS1 was downregulated in HCC tissues,but its role in HCC progression is unclear.Ultrasound targeted microbubble destruction mediated gene transfection is a new method to overexpress genes.AIM To study the role of ultrasound microbubbles(UTMBs)mediated HAND2-AS1 in the progression of HCC,in order to provide a new reference for the treatment of HCC.METHODS In vitro,we transfected HAND2-AS1 siRNA into HepG2 cells by UTMBs,and detected cell proliferation,apoptosis,invasion and epithelial-mesenchymal transition(EMT)by cell counting kit-8 assay,flow cytometry,Transwell invasion assay and Western blotting,respectively.In addition,we transfected miR-837-5p mimic into UTMBs treated cells and observed the changes of cell behavior.Next,the UTMBs treated HepG2 cells were transfected together with miR-837-5p mimic and tissue inhibitor of matrix metalloproteinase-2(TIMP2)overexpression vector,and we detected cell proliferation,apoptosis,invasion and EMT.In vivo,we established a mouse model of subcutaneous transplantation of HepG2 cells and observed the effect of HAND2-AS1 silencing on tumor formation ability.RESULTS We found that UTMBs carrying HAND2-AS1 restricted cell proliferation,invasion,and EMT,encouraged apoptosis,and HAND2-AS1 silencing eliminated the effect of UTMBs.Additionally,miR-873-5p targets the gene HAND2-AS1,which also targets the 3’UTR of TIMP2.And miR-873-5p mimic counteracted the impact of HAND2-AS1.Further,miR-873-5p mimic solely or in combination with pcDNA-TIMP2 had been transformed into HepG2 cells exposed to UTMBs.We discovered that TIMP2 reversed the effect of miR-873-5p mimic caused by the blocked signalling cascade for matrix metalloproteinase(MMP)2/MMP9.In vivo results showed that HAND2-AS1 silencing significantly inhibited tumor formation in mice.CONCLUSION LncRNA HAND2-AS1 promotes TIMP2 expression by targeting miR-873-5p to inhibit HepG2 cell growth and delay HCC progression.展开更多
Heart failure with preserved ejection fraction(HFpEF)is a heterogeneous syndrome with various comorbidities,multiple cardiac and extracardiac pathophysiologic abnormalities,and diverse phenotypic presentations.Since H...Heart failure with preserved ejection fraction(HFpEF)is a heterogeneous syndrome with various comorbidities,multiple cardiac and extracardiac pathophysiologic abnormalities,and diverse phenotypic presentations.Since HFpEF is a heterogeneous disease with different phenotypes,individualized treatment is required.HFpEF with type 2 diabetes mellitus(T2DM)represents a specific phenotype of HFpEF,with about 45%-50% of HFpEF patients suffering from T2DM.Systemic inflammation associated with dysregulated glucose metabolism is a critical pathological mechanism of HFpEF with T2DM,which is intimately related to the expansion and dysfunction(inflammation and hypermetabolic activity)of epicardial adipose tissue(EAT).EAT is well established as a very active endocrine organ that can regulate the pathophysiological processes of HFpEF with T2DM through the paracrine and endocrine mechanisms.Therefore,suppressing abnormal EAT expansion may be a promising therapeutic strategy for HFpEF with T2DM.Although there is no treatment specifically for EAT,lifestyle management,bariatric surgery,and some pharmaceutical interventions(anti-cytokine drugs,statins,proprotein convertase subtilisin/kexin type 9 inhibitors,metformin,glucagon-like peptide-1 receptor agonists,and especially sodium-glucose cotransporter-2 inhibitors)have been shown to attenuate the inflammatory response or expansion of EAT.Importantly,these treatments may be beneficial in improving the clinical symptoms or prognosis of patients with HFpEF.Accordingly,well-designed randomized controlled trials are needed to validate the efficacy of current therapies.In addition,more novel and effective therapies targeting EAT are needed in the future.展开更多
Objective:To investigate the therapeutic effect of Bai Hu Ren Shen Soup(BHRSS)on type 2 diabetes mellitus(T2DM)rats and explore whether its therapeutic effect is achieved by promoting autophagy in the pancreas tissue ...Objective:To investigate the therapeutic effect of Bai Hu Ren Shen Soup(BHRSS)on type 2 diabetes mellitus(T2DM)rats and explore whether its therapeutic effect is achieved by promoting autophagy in the pancreas tissue of T2DM rats.Methods:Thirty male standard deviation rats were equally divided into normal control group,T2DM group and BHRSS group.Firstly,the therapeutic effect of BHRSS on T2DM was evaluated by biochemical indices in serum and pathological changes in the pancreas tissue of rats in each group after modeling and medication.Then,the levels of microtubule-associated protein 1 light chain 3(LC3)protein and p62 protein in the pancreas tissue of rats in each group after BHRSS intervention were detected by Western blot.Results:BHRSS intervention significantly reduced the levels of blood sugar,liver and kidney function,and other related biochemical indices in the serum of T2DM rats,and effectively improved the pathological changes in the pancreas tissue of T2DM rats.In addition,Western blot results showed that the expression levels of autophagy-related protein LC3 protein in the pancreas tissue of rats were increased,and the expression level of p62 protein was decreased after BHRSS intervention.Conclusion:BHRSS has a clear therapeutic effect on T2DM model rats,which may be related to that increase of autophagy protein LC3 and the decrease of p62 protein level in the pancreas tissue.展开更多
AIM:To compare the performance of three commercially available anti-human epidermalgrowth factor receptor 2(HER2)antibodies in whole-tissue sections and tissue microarrays(TMAs)of a series of gastric tumors.METHODS:We...AIM:To compare the performance of three commercially available anti-human epidermalgrowth factor receptor 2(HER2)antibodies in whole-tissue sections and tissue microarrays(TMAs)of a series of gastric tumors.METHODS:We present a comparative analysis of three anti-HER2 antibodies(HercepTest,4B5 and SP3)using TMA and whole-tissue sections prepared from the same paraffin blocks of 199 gastric adenocarcinomas operated upon between January 2004 and December2008 at a Brazilian cancer hospital.The data on the patients’age,sex,the anatomical location of the tumor and the Lauren’s histological classification were collected from clinical and pathological records.The immunohistochemical(IHC)results were examined by two pathologists and the cases were classified as positive(3+),equivocal(2+)and negative(0 or 1+),according to the criteria of the IHC scoring system of gastric cancer.TMAs and whole-tissue sections were evaluated separately and independently.All cases yielding discordant IHC results and/or scored as 2+were subjected to dual-color in situ hybridization in order to determine the final HER2 status.Besides determining the sensitivity and predictive value for HER2-positive status,we measured the accuracy of each antibody by calculating the area under the receiver operating characteristic(ROC)curve.The agreement between the results obtained using the TMAs and those obtained using the whole-tissue sections was assessed by means of Kappa coefficient.RESULTS:Intratumoral heterogeneity of HER2 expression was observed with all antibodies.HER2-positive expression(3+)in the whole-tissue sections was observed in 23 cases(11.6%)using the 4B5 antibody,in 18 cases(9.1%)using the SP3 antibody and in 10 cases(5.1%)using the HercepTest antibody.In the TMAs,11 positive cases(5.6%)were identified using SP3 antibody,9(4.6%)using the 4B5 antibody and 6(3%)using the HercepTest antibody.The sensitivity using whole-tissue sections and TMA,respectively,was 95.2%and 42.9%with 4B5,90.5%and 66.7%with SP3 and 47.6%and42.9%with HercepTest.The accuracy,calculated from the area under the ROC curve,using whole-tissue sections and TMA,respectively,was 0.91 and 0.79 by 4B5,0.86 and 0.80 by SP3 and 0.73 and 0.71 by HercepTest.The concordance of the results obtained using wholetissue sections and TMA was 97.4%(Kappa 0.75)using HercepTest,85.6%(Kappa 0.56)using SP3 and 84.1%(Kappa 0.38)using 4B5.CONCLUSION:The use of the 4B5 antibody on wholetissue sections was the most accurate IHC method for evaluating HER2 expression in gastric adenocarcinoma.展开更多
Objective:To investigate the effect of acute renal ischemia reperfusion on brain tissue.Methods:Fourty eight rats were randomly divided into four groups(n=12):sham operation group,30 min ischemia 60 min reperfusion gr...Objective:To investigate the effect of acute renal ischemia reperfusion on brain tissue.Methods:Fourty eight rats were randomly divided into four groups(n=12):sham operation group,30 min ischemia 60 min reperfusion group,60 min ischemia 60 min reperfusion group,and120 min ischemia 60 min reperfusion group.The brain tissues were taken after the experiment.TUNEL assay was used to detect the brain cell apoptosis,and western blot was used to detect the expression of apoptosis-related proteins and inflammatory factors.Results:Renal ischemiareperiusion induced apoptosis of brain tissues,and the apoptosis increased with prolongation of ischemia time.The detection at the molecular level showed decreased Bcl-2 expression,increased Bax expression,upreguiated expression of NF- κB and its downstream factor COX-2/PGE2.Conclusions:Acute renal ischemia-reperfusion can cause brain tissue damage,manifested as induced brain tissues apoptosis and inflammation activation.展开更多
BACKGROUND: Pancreatic cancer development and progression is driven by the accumulation of genetic changes. In this study we constructed tissue microarray containing specimens from pancreatic cancer, adjacent non-canc...BACKGROUND: Pancreatic cancer development and progression is driven by the accumulation of genetic changes. In this study we constructed tissue microarray containing specimens from pancreatic cancer, adjacent non-cancer tissue and normal tissue to survey the expression of p53, p16 and cyclooxyganase-2 (COX-2). METHODS: Tissue microarray containing 337 specimens from different stages of pancreatic cancer, adjacent noncancer tissue and normal tissues was constructed, and the expression of p53, p16 and COX-2 was assayed by immunohistochemistry to consecutive formalin-fixed tissue microarray sections. RESULTS: The expression of p53, p16 and COX-2 was significantly higher in tumorous tissues than in non-tumorons ones. A significant relationship was observed between p53 and COX-2, or p16 and COX-2. But no obvious correlation was seen between p53 and p16 expressions. Logistic regression analysis showed p53 and COX-2 as dependent predictors in pancreatic carcinogenesis, and a reciprocal relationship to neoplastic progression between p53 and COX-2. CONCLUSION: Combination analysis of p53 and COX-2 may be useful in predicting pancreatic carcinogenesis.展开更多
Objective To study the differential patterns of gene expression in skeletal muscle and adipose tissue between type 2 diabetes mellitus (T2DM) patients and healthy subjects using DNA microarray analysis, Methods T2DM...Objective To study the differential patterns of gene expression in skeletal muscle and adipose tissue between type 2 diabetes mellitus (T2DM) patients and healthy subjects using DNA microarray analysis, Methods T2DM patiens were divided into female group, young male group and old male group. DNA microarray analysis and quantitative real-time PCR were carried out to anaIyze the relation between gene expressions and T2DM. Results The mRNA expression of 298, 578, and 350 genes was changed in the skeletal muscle of diabetes mellitus patients compared with control subjects. The 1320, 1143, and 2847 genes were modified in adipose tissue of the three groups. Among the genes surveyed, the change of 25 and 39 gene transcripts in skeletal muscle and adipose tissue was ≥2 folds, These differentially expressed genes were classified into 15 categories according to their functions. Conclusion New genes are found and T2DM can be prevented or cured.展开更多
Twelve healthy rats were divided into the T-2 toxin group receiving gavage of 1 mg/kg T-2 toxin and the control group receiving gavage of normal saline. Total relative concentrations of T-2 toxin and HT-2 toxin in the...Twelve healthy rats were divided into the T-2 toxin group receiving gavage of 1 mg/kg T-2 toxin and the control group receiving gavage of normal saline. Total relative concentrations of T-2 toxin and HT-2 toxin in the skeletal system(thighbone, knee joints, and costal cartilage) were significantly higher than those in the heart, liver, and kidneys(P 〈 0.05). The relative concentrations of T-2 toxin and HT-2 toxin in the skeletal system(thighbone and costal cartilage) were also significantly higher than those in the heart, liver, and kidneys. The rats administered T-2 toxin showed rapid metabolism compared with that in rats administered HT-2 toxin, and the metabolic conversion rates in the different tissues were 68.20%-90.70%.展开更多
The effect and potential molecular mechanisms of berberine on gluconeogenesis in skeletal muscles and adipose tissues were investigated.After adaptive feeding for one week,8 rats were randomly selected as the normal g...The effect and potential molecular mechanisms of berberine on gluconeogenesis in skeletal muscles and adipose tissues were investigated.After adaptive feeding for one week,8 rats were randomly selected as the normal group and fed on a standard diet.The remaining 32 rats were fed on a high-fat diet and given an intravenous injection of streptozotocin(STZ)for 2 weeks to induce the diabetic models.The diabetic rat models were confirmed by oral glucose tolerance test(OGTT)and randomly divided into 4 groups(n=8 each),which were all fed on a high-fat diet.Berberine(3 g/kg per day)or metformin(183 mg/kg per day)was intragastrically administered to the diabetic rats for 12 weeks,serving as berberine group and metformin group respectively.5-aminoimidazole-4-carboxamide1-β-D-ribofuranoside[AICAR,an agonist of AMP-activated protein kinase(AMPK),0.5 mg/kg per day]was subcutaneously injected to the diabetic rats for 12 weeks,serving as AICAR group.The remaining 8 diabetic rats served as the model group,which was given a 0.5%carboxyl methylcellulose solution by oral gavage.Fasting serum insulin(FINS),OGTT as well as lipid parameters were tested by commercial kit.The protein levels of liver kinase B1(LKB1),AMPK,phosphorylated AMP-activated protein kinase(p-AMPK),transducer of regulated CREB activity 2(TORC2),phosphorylated transducer of regulated CREB activity 2(p-TORC2),phosphoenolpyruvate carboxykinase(PEPCK),and glucose-6-phosphatase(G6Pase)in skeletal muscles and adipose tissues were examined by Western blotting.The results showed that berberine significantly decreased the body weight,plasma glucose,insulin levels,and homeostatic model assessment for insulin resistance(HOMA-IR)of diabetic rats compared with those in the model group.Meanwhile,the serum total triglyceride(TG),total cholesterol(TC),and low-density lipoprotein cholesterol(LDL-C)levels were markedly decreased and high-density lipoprotein cholesterol(HDL-C)level was significantly increased after the treatment with berberine.In addition,we found that berberine significantly increased the expression of p-AMPK and LKB1,while decreasing the p-TORC2 levels in skeletal muscles and adipose tissues.Moreover,the expression of PEPCK and G6Pase was significantly down-regulated after the treatment with berberine compared to the model group.It was suggested that the mechanism by which berberine inhibited peripheral tissue gluconeogenesis may be attributed to the activation of the LKB1-AMPK-TORC2 signaling pathway.展开更多
The aim of this study was to evaluate the efficacy of mosaicplasty with tissue-engineered cartilage for the treatment of osteochondral defects in a pig model with advanced MR technique. Eight adolescent miniature pigs...The aim of this study was to evaluate the efficacy of mosaicplasty with tissue-engineered cartilage for the treatment of osteochondral defects in a pig model with advanced MR technique. Eight adolescent miniature pigs were used. The right knee underwent mosaicplasty with tissue-engineered cartilage for treatment of focal osteochondral defects, while the left knee was repaired via single mosaicplasty as controls. At 6, 12, 18 and 26 weeks after surgery, repair tissue was evaluated by magnetic resonance imaging (MRI) with the cartilage repair tissue (MOCART) scoring system and T2 mapping. Then, the results of MRI for 26 weeks were compared with findings of macroscopic and histologic studies. The MOCART scores showed that the repaired tissue of the tissue-engineered cartilage group was statistically better than that of controls (P 〈 0.001). A significant correlation was found between macroscopic and MOCART scores (P 〈 0.001). Comparable mean T2 values were found between adjacent cartilage and repair tissue in the experimental group (P 〉 0.05). For zonal T2 value evaluation, there were no significant zonal T2 differences for repair tissue in controls (P 〉 0.05). For the experimental group, zonal T2 variation was found in repair tissue (P 〈 0.05). MRI, macroscopy and histology showed better repair results and bony incorporation in mosaicplasty with the tissue-engi- neered cartilage group than those of the single mosaicplasty group. Mosaicplasty with the tissue-engineered cartilage is a promising approach to repair osteochodndral defects. Morphological MRI and T2 mapping provide a non-invasive method for monitoring the maturation and integration of cartilage repair tissue in vivo.展开更多
AIM: To explore the expression and clinicopathological significance of cyclooxygenase-2 (COX-2) and microvessel density (MVD) in gastric carcinogenesis, and to investigate their roles in the invasion and the relations...AIM: To explore the expression and clinicopathological significance of cyclooxygenase-2 (COX-2) and microvessel density (MVD) in gastric carcinogenesis, and to investigate their roles in the invasion and the relationship between biological behaviors and prognosis of gastric cancer. METHODS: Using Envision immunohistochemistry, COX-2 and CD34 expressions in gastric cancer tissue array were examined. MVD was counted and the relationship between the biological behaviors and prognosis was analyzed. RESULTS: The expression of COX-2 in gastric cancer tissue was significantly higher than that in normal mucosa (χ2 = 12.191, P < 0.05). The over-expression of COX-2 in gastric cancer was obviously related to metastasis and depth of invasion (χ2 = 6.315, P < 0.05), but not related to the histological type and Borrmann type (χ2 = 5.391 and χ2 = 2.228, respectively). Moreover, MVD in gastric cancer tissues was significantly higher than that in the normal mucosa (65.49 ± 20.64 vs 36.21 ± 18.47, t/F = 7.53, P < 0. 05). MVD was related to the histologic type and metastasis (t/F = 3.68 and t/F = 4.214, respectively, P < 0. 05), but not related to the depth of invasion and Borrmann type (t/F = 0.583 and t/F = 0.459, respectively). MVD in COX-2-positive tissues was markedly higher compared to COX-2-negative tissues, indicating a positive correlation between COX-2 expression and MVD (t = 13.12, P < 0. 05). CONCLUSION: Tissue microarray (TMA) is a powerful tool for rapid identifi cation of the molecular alterations in gastric cancer. COX-2 expression, via inducingangiogenesis, may play an important role in gastric carcinogenesis. It could be served as a determinant factor for clinical prognosis and curative effect.展开更多
To compare intervertebral location L2-L3 with L4-L5 as landmarks for measuring abdominal fat distribution and to determine critical levels of visceral adipose tissue (VAT) at those planes, exceeding which may lead t...To compare intervertebral location L2-L3 with L4-L5 as landmarks for measuring abdominal fat distribution and to determine critical levels of visceral adipose tissue (VAT) at those planes, exceeding which may lead to the development of type 2 diabetes. Methods: Abdominal fat distribution was measured using computed tomography(CT) in 29 diabetics (19 male, 10 female) and 30 non-diabetics (18 male, 12 female). CT images obtained at two intervertebral locations L2-L3 and L4-L5 were used to measure the areas of total fat, VAT and subcutaneous adipose tissue (SCAT) using slice thickness of 5mm and an attenuation range from -190 to -30 Hounsfield units (HU). Data were analyzed using logistic regression and Receiver-operating characteristic (ROC) analysis. Results: At L2-L3, diabetes and obesity were correctly classified at 91.53% and 83.05% respectively, while at L4-L5, the same were correctly classified at 84.75% and 88.14% respectively. VAT compared to SCAT, had significantly higher correctly classified percent values for predicting diabetes in both measurement sites. At L2-L3, VAT≥177.29 cm2 or VAT ≥51.52% of the total fat area had the highest correctly classified value for predicting diabetes in men, while VAT ≥ 132.27 cm2 or VAT≥45.7% of the total fat area had the highest correctly classified value for predicting diabetes in women. At LA-L5, VAT≥ 130.82 cm2 or VAT≥45.5,$% of the total fat area had the highest correctly classified value for predicting diabetes in men, while VAT≥ 118.56 cm2 or VAT≥32.24% of the total fat area had the highest correctly classified value for predicting diabetes in women. Conclusion: L2-L3 plane is a better landmark for measuring abdominal fat distribution for predicting diabetes, while abdominal fat distribution measured at L4-L5 has better association with obesity. Regardless of the measurement site, VAT compared to SCAT, has significantly stronger association with diabetes.展开更多
The callipyge (CLPG) phenotype, exhibiting polar overdominance (POD), is an inherited skeletal muscle hypertrophy described in sheep. The callipyge locus maps to the distal portion of ovine chromosome 18 within th...The callipyge (CLPG) phenotype, exhibiting polar overdominance (POD), is an inherited skeletal muscle hypertrophy described in sheep. The callipyge locus maps to the distal portion of ovine chromosome 18 within the DLKI-GTL2 region and corresponds to human chromosome 14 and mouse chromosome 12. The POD phenomenon is confirmed to the homologous region of swine chromosome 7. In order to clone and investigate the expression of porcine GTL2 gene, DNA and RNA samples from 60-day-old F1 animals, generated with reciprocal crosses between Large White and Meishan breeds and their parents, were used. The authors showed that porcine GTL2 acted as a uoncoding RNA. cDNA samples exhibited maternal expression of the gene in the heart, liver, spleen, lung, kidney, stomach, small intestine, skeletal muscle, and fat in pigs, and a unique tissue-specific expression different from that of humans and mice. These results indicated that the gene was conserved in the pig, human, mouse, and bovine. It will be of interest to further study the gene functions in muscle growth and fat deposition.展开更多
文摘BACKGROUND Increasing data indicated that long noncoding RNAs(lncRNAs)were directly or indirectly involved in the occurrence and development of tumors,including hepatocellular carcinoma(HCC).Recent studies had found that the expression of lncRNA HAND2-AS1 was downregulated in HCC tissues,but its role in HCC progression is unclear.Ultrasound targeted microbubble destruction mediated gene transfection is a new method to overexpress genes.AIM To study the role of ultrasound microbubbles(UTMBs)mediated HAND2-AS1 in the progression of HCC,in order to provide a new reference for the treatment of HCC.METHODS In vitro,we transfected HAND2-AS1 siRNA into HepG2 cells by UTMBs,and detected cell proliferation,apoptosis,invasion and epithelial-mesenchymal transition(EMT)by cell counting kit-8 assay,flow cytometry,Transwell invasion assay and Western blotting,respectively.In addition,we transfected miR-837-5p mimic into UTMBs treated cells and observed the changes of cell behavior.Next,the UTMBs treated HepG2 cells were transfected together with miR-837-5p mimic and tissue inhibitor of matrix metalloproteinase-2(TIMP2)overexpression vector,and we detected cell proliferation,apoptosis,invasion and EMT.In vivo,we established a mouse model of subcutaneous transplantation of HepG2 cells and observed the effect of HAND2-AS1 silencing on tumor formation ability.RESULTS We found that UTMBs carrying HAND2-AS1 restricted cell proliferation,invasion,and EMT,encouraged apoptosis,and HAND2-AS1 silencing eliminated the effect of UTMBs.Additionally,miR-873-5p targets the gene HAND2-AS1,which also targets the 3’UTR of TIMP2.And miR-873-5p mimic counteracted the impact of HAND2-AS1.Further,miR-873-5p mimic solely or in combination with pcDNA-TIMP2 had been transformed into HepG2 cells exposed to UTMBs.We discovered that TIMP2 reversed the effect of miR-873-5p mimic caused by the blocked signalling cascade for matrix metalloproteinase(MMP)2/MMP9.In vivo results showed that HAND2-AS1 silencing significantly inhibited tumor formation in mice.CONCLUSION LncRNA HAND2-AS1 promotes TIMP2 expression by targeting miR-873-5p to inhibit HepG2 cell growth and delay HCC progression.
文摘Heart failure with preserved ejection fraction(HFpEF)is a heterogeneous syndrome with various comorbidities,multiple cardiac and extracardiac pathophysiologic abnormalities,and diverse phenotypic presentations.Since HFpEF is a heterogeneous disease with different phenotypes,individualized treatment is required.HFpEF with type 2 diabetes mellitus(T2DM)represents a specific phenotype of HFpEF,with about 45%-50% of HFpEF patients suffering from T2DM.Systemic inflammation associated with dysregulated glucose metabolism is a critical pathological mechanism of HFpEF with T2DM,which is intimately related to the expansion and dysfunction(inflammation and hypermetabolic activity)of epicardial adipose tissue(EAT).EAT is well established as a very active endocrine organ that can regulate the pathophysiological processes of HFpEF with T2DM through the paracrine and endocrine mechanisms.Therefore,suppressing abnormal EAT expansion may be a promising therapeutic strategy for HFpEF with T2DM.Although there is no treatment specifically for EAT,lifestyle management,bariatric surgery,and some pharmaceutical interventions(anti-cytokine drugs,statins,proprotein convertase subtilisin/kexin type 9 inhibitors,metformin,glucagon-like peptide-1 receptor agonists,and especially sodium-glucose cotransporter-2 inhibitors)have been shown to attenuate the inflammatory response or expansion of EAT.Importantly,these treatments may be beneficial in improving the clinical symptoms or prognosis of patients with HFpEF.Accordingly,well-designed randomized controlled trials are needed to validate the efficacy of current therapies.In addition,more novel and effective therapies targeting EAT are needed in the future.
文摘Objective:To investigate the therapeutic effect of Bai Hu Ren Shen Soup(BHRSS)on type 2 diabetes mellitus(T2DM)rats and explore whether its therapeutic effect is achieved by promoting autophagy in the pancreas tissue of T2DM rats.Methods:Thirty male standard deviation rats were equally divided into normal control group,T2DM group and BHRSS group.Firstly,the therapeutic effect of BHRSS on T2DM was evaluated by biochemical indices in serum and pathological changes in the pancreas tissue of rats in each group after modeling and medication.Then,the levels of microtubule-associated protein 1 light chain 3(LC3)protein and p62 protein in the pancreas tissue of rats in each group after BHRSS intervention were detected by Western blot.Results:BHRSS intervention significantly reduced the levels of blood sugar,liver and kidney function,and other related biochemical indices in the serum of T2DM rats,and effectively improved the pathological changes in the pancreas tissue of T2DM rats.In addition,Western blot results showed that the expression levels of autophagy-related protein LC3 protein in the pancreas tissue of rats were increased,and the expression level of p62 protein was decreased after BHRSS intervention.Conclusion:BHRSS has a clear therapeutic effect on T2DM model rats,which may be related to that increase of autophagy protein LC3 and the decrease of p62 protein level in the pancreas tissue.
文摘AIM:To compare the performance of three commercially available anti-human epidermalgrowth factor receptor 2(HER2)antibodies in whole-tissue sections and tissue microarrays(TMAs)of a series of gastric tumors.METHODS:We present a comparative analysis of three anti-HER2 antibodies(HercepTest,4B5 and SP3)using TMA and whole-tissue sections prepared from the same paraffin blocks of 199 gastric adenocarcinomas operated upon between January 2004 and December2008 at a Brazilian cancer hospital.The data on the patients’age,sex,the anatomical location of the tumor and the Lauren’s histological classification were collected from clinical and pathological records.The immunohistochemical(IHC)results were examined by two pathologists and the cases were classified as positive(3+),equivocal(2+)and negative(0 or 1+),according to the criteria of the IHC scoring system of gastric cancer.TMAs and whole-tissue sections were evaluated separately and independently.All cases yielding discordant IHC results and/or scored as 2+were subjected to dual-color in situ hybridization in order to determine the final HER2 status.Besides determining the sensitivity and predictive value for HER2-positive status,we measured the accuracy of each antibody by calculating the area under the receiver operating characteristic(ROC)curve.The agreement between the results obtained using the TMAs and those obtained using the whole-tissue sections was assessed by means of Kappa coefficient.RESULTS:Intratumoral heterogeneity of HER2 expression was observed with all antibodies.HER2-positive expression(3+)in the whole-tissue sections was observed in 23 cases(11.6%)using the 4B5 antibody,in 18 cases(9.1%)using the SP3 antibody and in 10 cases(5.1%)using the HercepTest antibody.In the TMAs,11 positive cases(5.6%)were identified using SP3 antibody,9(4.6%)using the 4B5 antibody and 6(3%)using the HercepTest antibody.The sensitivity using whole-tissue sections and TMA,respectively,was 95.2%and 42.9%with 4B5,90.5%and 66.7%with SP3 and 47.6%and42.9%with HercepTest.The accuracy,calculated from the area under the ROC curve,using whole-tissue sections and TMA,respectively,was 0.91 and 0.79 by 4B5,0.86 and 0.80 by SP3 and 0.73 and 0.71 by HercepTest.The concordance of the results obtained using wholetissue sections and TMA was 97.4%(Kappa 0.75)using HercepTest,85.6%(Kappa 0.56)using SP3 and 84.1%(Kappa 0.38)using 4B5.CONCLUSION:The use of the 4B5 antibody on wholetissue sections was the most accurate IHC method for evaluating HER2 expression in gastric adenocarcinoma.
基金funded by the Henan Province Education Departent Natural Science Research Item(2010A320020)
文摘Objective:To investigate the effect of acute renal ischemia reperfusion on brain tissue.Methods:Fourty eight rats were randomly divided into four groups(n=12):sham operation group,30 min ischemia 60 min reperfusion group,60 min ischemia 60 min reperfusion group,and120 min ischemia 60 min reperfusion group.The brain tissues were taken after the experiment.TUNEL assay was used to detect the brain cell apoptosis,and western blot was used to detect the expression of apoptosis-related proteins and inflammatory factors.Results:Renal ischemiareperiusion induced apoptosis of brain tissues,and the apoptosis increased with prolongation of ischemia time.The detection at the molecular level showed decreased Bcl-2 expression,increased Bax expression,upreguiated expression of NF- κB and its downstream factor COX-2/PGE2.Conclusions:Acute renal ischemia-reperfusion can cause brain tissue damage,manifested as induced brain tissues apoptosis and inflammation activation.
基金The study was supported by a grant from the National 863 program (2002AA2Z2021).
文摘BACKGROUND: Pancreatic cancer development and progression is driven by the accumulation of genetic changes. In this study we constructed tissue microarray containing specimens from pancreatic cancer, adjacent non-cancer tissue and normal tissue to survey the expression of p53, p16 and cyclooxyganase-2 (COX-2). METHODS: Tissue microarray containing 337 specimens from different stages of pancreatic cancer, adjacent noncancer tissue and normal tissues was constructed, and the expression of p53, p16 and COX-2 was assayed by immunohistochemistry to consecutive formalin-fixed tissue microarray sections. RESULTS: The expression of p53, p16 and COX-2 was significantly higher in tumorous tissues than in non-tumorons ones. A significant relationship was observed between p53 and COX-2, or p16 and COX-2. But no obvious correlation was seen between p53 and p16 expressions. Logistic regression analysis showed p53 and COX-2 as dependent predictors in pancreatic carcinogenesis, and a reciprocal relationship to neoplastic progression between p53 and COX-2. CONCLUSION: Combination analysis of p53 and COX-2 may be useful in predicting pancreatic carcinogenesis.
基金supported by the National High Technology Research and Development Program of China (863 Program No. 2001AA221161)the National Key Technologies R & D Program of China (No. 2002BA711A05)
文摘Objective To study the differential patterns of gene expression in skeletal muscle and adipose tissue between type 2 diabetes mellitus (T2DM) patients and healthy subjects using DNA microarray analysis, Methods T2DM patiens were divided into female group, young male group and old male group. DNA microarray analysis and quantitative real-time PCR were carried out to anaIyze the relation between gene expressions and T2DM. Results The mRNA expression of 298, 578, and 350 genes was changed in the skeletal muscle of diabetes mellitus patients compared with control subjects. The 1320, 1143, and 2847 genes were modified in adipose tissue of the three groups. Among the genes surveyed, the change of 25 and 39 gene transcripts in skeletal muscle and adipose tissue was ≥2 folds, These differentially expressed genes were classified into 15 categories according to their functions. Conclusion New genes are found and T2DM can be prevented or cured.
基金partially supported by National Natural Scientific Foundation of China[81620108026,81302393]
文摘Twelve healthy rats were divided into the T-2 toxin group receiving gavage of 1 mg/kg T-2 toxin and the control group receiving gavage of normal saline. Total relative concentrations of T-2 toxin and HT-2 toxin in the skeletal system(thighbone, knee joints, and costal cartilage) were significantly higher than those in the heart, liver, and kidneys(P 〈 0.05). The relative concentrations of T-2 toxin and HT-2 toxin in the skeletal system(thighbone and costal cartilage) were also significantly higher than those in the heart, liver, and kidneys. The rats administered T-2 toxin showed rapid metabolism compared with that in rats administered HT-2 toxin, and the metabolic conversion rates in the different tissues were 68.20%-90.70%.
基金This project was supported by the National Natural Science Foundation of China(No.81673757 and No.81603652).
文摘The effect and potential molecular mechanisms of berberine on gluconeogenesis in skeletal muscles and adipose tissues were investigated.After adaptive feeding for one week,8 rats were randomly selected as the normal group and fed on a standard diet.The remaining 32 rats were fed on a high-fat diet and given an intravenous injection of streptozotocin(STZ)for 2 weeks to induce the diabetic models.The diabetic rat models were confirmed by oral glucose tolerance test(OGTT)and randomly divided into 4 groups(n=8 each),which were all fed on a high-fat diet.Berberine(3 g/kg per day)or metformin(183 mg/kg per day)was intragastrically administered to the diabetic rats for 12 weeks,serving as berberine group and metformin group respectively.5-aminoimidazole-4-carboxamide1-β-D-ribofuranoside[AICAR,an agonist of AMP-activated protein kinase(AMPK),0.5 mg/kg per day]was subcutaneously injected to the diabetic rats for 12 weeks,serving as AICAR group.The remaining 8 diabetic rats served as the model group,which was given a 0.5%carboxyl methylcellulose solution by oral gavage.Fasting serum insulin(FINS),OGTT as well as lipid parameters were tested by commercial kit.The protein levels of liver kinase B1(LKB1),AMPK,phosphorylated AMP-activated protein kinase(p-AMPK),transducer of regulated CREB activity 2(TORC2),phosphorylated transducer of regulated CREB activity 2(p-TORC2),phosphoenolpyruvate carboxykinase(PEPCK),and glucose-6-phosphatase(G6Pase)in skeletal muscles and adipose tissues were examined by Western blotting.The results showed that berberine significantly decreased the body weight,plasma glucose,insulin levels,and homeostatic model assessment for insulin resistance(HOMA-IR)of diabetic rats compared with those in the model group.Meanwhile,the serum total triglyceride(TG),total cholesterol(TC),and low-density lipoprotein cholesterol(LDL-C)levels were markedly decreased and high-density lipoprotein cholesterol(HDL-C)level was significantly increased after the treatment with berberine.In addition,we found that berberine significantly increased the expression of p-AMPK and LKB1,while decreasing the p-TORC2 levels in skeletal muscles and adipose tissues.Moreover,the expression of PEPCK and G6Pase was significantly down-regulated after the treatment with berberine compared to the model group.It was suggested that the mechanism by which berberine inhibited peripheral tissue gluconeogenesis may be attributed to the activation of the LKB1-AMPK-TORC2 signaling pathway.
基金supported by the National Natural Science Foundation ofChina(No.81000800)
文摘The aim of this study was to evaluate the efficacy of mosaicplasty with tissue-engineered cartilage for the treatment of osteochondral defects in a pig model with advanced MR technique. Eight adolescent miniature pigs were used. The right knee underwent mosaicplasty with tissue-engineered cartilage for treatment of focal osteochondral defects, while the left knee was repaired via single mosaicplasty as controls. At 6, 12, 18 and 26 weeks after surgery, repair tissue was evaluated by magnetic resonance imaging (MRI) with the cartilage repair tissue (MOCART) scoring system and T2 mapping. Then, the results of MRI for 26 weeks were compared with findings of macroscopic and histologic studies. The MOCART scores showed that the repaired tissue of the tissue-engineered cartilage group was statistically better than that of controls (P 〈 0.001). A significant correlation was found between macroscopic and MOCART scores (P 〈 0.001). Comparable mean T2 values were found between adjacent cartilage and repair tissue in the experimental group (P 〉 0.05). For zonal T2 value evaluation, there were no significant zonal T2 differences for repair tissue in controls (P 〉 0.05). For the experimental group, zonal T2 variation was found in repair tissue (P 〈 0.05). MRI, macroscopy and histology showed better repair results and bony incorporation in mosaicplasty with the tissue-engi- neered cartilage group than those of the single mosaicplasty group. Mosaicplasty with the tissue-engineered cartilage is a promising approach to repair osteochodndral defects. Morphological MRI and T2 mapping provide a non-invasive method for monitoring the maturation and integration of cartilage repair tissue in vivo.
文摘AIM: To explore the expression and clinicopathological significance of cyclooxygenase-2 (COX-2) and microvessel density (MVD) in gastric carcinogenesis, and to investigate their roles in the invasion and the relationship between biological behaviors and prognosis of gastric cancer. METHODS: Using Envision immunohistochemistry, COX-2 and CD34 expressions in gastric cancer tissue array were examined. MVD was counted and the relationship between the biological behaviors and prognosis was analyzed. RESULTS: The expression of COX-2 in gastric cancer tissue was significantly higher than that in normal mucosa (χ2 = 12.191, P < 0.05). The over-expression of COX-2 in gastric cancer was obviously related to metastasis and depth of invasion (χ2 = 6.315, P < 0.05), but not related to the histological type and Borrmann type (χ2 = 5.391 and χ2 = 2.228, respectively). Moreover, MVD in gastric cancer tissues was significantly higher than that in the normal mucosa (65.49 ± 20.64 vs 36.21 ± 18.47, t/F = 7.53, P < 0. 05). MVD was related to the histologic type and metastasis (t/F = 3.68 and t/F = 4.214, respectively, P < 0. 05), but not related to the depth of invasion and Borrmann type (t/F = 0.583 and t/F = 0.459, respectively). MVD in COX-2-positive tissues was markedly higher compared to COX-2-negative tissues, indicating a positive correlation between COX-2 expression and MVD (t = 13.12, P < 0. 05). CONCLUSION: Tissue microarray (TMA) is a powerful tool for rapid identifi cation of the molecular alterations in gastric cancer. COX-2 expression, via inducingangiogenesis, may play an important role in gastric carcinogenesis. It could be served as a determinant factor for clinical prognosis and curative effect.
文摘To compare intervertebral location L2-L3 with L4-L5 as landmarks for measuring abdominal fat distribution and to determine critical levels of visceral adipose tissue (VAT) at those planes, exceeding which may lead to the development of type 2 diabetes. Methods: Abdominal fat distribution was measured using computed tomography(CT) in 29 diabetics (19 male, 10 female) and 30 non-diabetics (18 male, 12 female). CT images obtained at two intervertebral locations L2-L3 and L4-L5 were used to measure the areas of total fat, VAT and subcutaneous adipose tissue (SCAT) using slice thickness of 5mm and an attenuation range from -190 to -30 Hounsfield units (HU). Data were analyzed using logistic regression and Receiver-operating characteristic (ROC) analysis. Results: At L2-L3, diabetes and obesity were correctly classified at 91.53% and 83.05% respectively, while at L4-L5, the same were correctly classified at 84.75% and 88.14% respectively. VAT compared to SCAT, had significantly higher correctly classified percent values for predicting diabetes in both measurement sites. At L2-L3, VAT≥177.29 cm2 or VAT ≥51.52% of the total fat area had the highest correctly classified value for predicting diabetes in men, while VAT ≥ 132.27 cm2 or VAT≥45.7% of the total fat area had the highest correctly classified value for predicting diabetes in women. At LA-L5, VAT≥ 130.82 cm2 or VAT≥45.5,$% of the total fat area had the highest correctly classified value for predicting diabetes in men, while VAT≥ 118.56 cm2 or VAT≥32.24% of the total fat area had the highest correctly classified value for predicting diabetes in women. Conclusion: L2-L3 plane is a better landmark for measuring abdominal fat distribution for predicting diabetes, while abdominal fat distribution measured at L4-L5 has better association with obesity. Regardless of the measurement site, VAT compared to SCAT, has significantly stronger association with diabetes.
基金supported by theNational Natural Science Foundation of China(30571331).
文摘The callipyge (CLPG) phenotype, exhibiting polar overdominance (POD), is an inherited skeletal muscle hypertrophy described in sheep. The callipyge locus maps to the distal portion of ovine chromosome 18 within the DLKI-GTL2 region and corresponds to human chromosome 14 and mouse chromosome 12. The POD phenomenon is confirmed to the homologous region of swine chromosome 7. In order to clone and investigate the expression of porcine GTL2 gene, DNA and RNA samples from 60-day-old F1 animals, generated with reciprocal crosses between Large White and Meishan breeds and their parents, were used. The authors showed that porcine GTL2 acted as a uoncoding RNA. cDNA samples exhibited maternal expression of the gene in the heart, liver, spleen, lung, kidney, stomach, small intestine, skeletal muscle, and fat in pigs, and a unique tissue-specific expression different from that of humans and mice. These results indicated that the gene was conserved in the pig, human, mouse, and bovine. It will be of interest to further study the gene functions in muscle growth and fat deposition.