Duodenum Exclusion Alone Is Sufficient to Improve Glucose Metabolism in STZ-Induced Diabetes Rats

Background

Several studies have found that metabolic surgery can significantly improve glucose homeostasis; however, the intrinsic mechanisms remain unclear. Accumulating evidence suggests that duodenal bypass plays a crucial role in the treatment of type 2 diabetes mellitus (T2DM). Here, we aimed to evaluate the effect of duodenal reflux on glucose metabolism in T2DM.

Methods

A high-fat diet and low-dose streptozotocin (STZ) administration were used to induce T2DM in male rats, which were assigned to three experimental groups: sham operation (SO; n?=?10), new duodenal-jejunal bypass (NDJB; n?=?10), and new duodenal-jejunal bypass with a tube (NDJBT; n?=?10). Weight, food intake, oral glucose tolerance test (OGTT) results, glucagon-like peptide 1 (GLP-1) levels, and histopathology were assessed before or after surgery. Plain abdominal radiography was performed 1 week after the operation.

Results

Plain abdominal radiography indicated the occurrence of contrast agent reflux into the duodenum. The body weight and food intake in all three groups did not significantly differ before and after surgery. The NDJB and particularly the NDJBT groups exhibited better glucose tolerance, lower fasting blood glucose (FBG) levels, lower area under the curves for OGTT (AUC_OGTT) values, and higher GLP-1 levels, as compared with the sham group postoperatively. The villus height and crypt depth were both shorter in the biliopancreatic limb after NDJBT, as compared with those after SO and NDJB.

Conclusions

Thus, exclusion of the duodenum alone and tube placement can effectively prevent duodenal reflux and improve glucose homeostasis, which further suggests that the duodenum plays an important role in T2DM.

     

TEKT4 Promotes Papillary Thyroid Cancer Cell Proliferation,Colony Formation,and Metastasis through Activating PI3K/Akt Pathway

Thyroid carcinoma is the most common malignancy of the endocrine system worldwide, but its molecular mechanisms remain unclear. Some diseases are associated with TEKT4 gene. However, its role in thyroid carcinoma has yet to be fully examined. This study was designed to investigate the function of TEKT4 in papillary thyroid cancer (PTC). The effect of TEKT4 on aggressive behavior of PTC cell lines, namely, TPC1 and BCPAP, transfected with small interfering RNA was identified through cell proliferation, colony formation, migration, and invasion. Our previous study revealed that TEKT4 may be vital in PTC. In in vitro experiments, TEKT4 downregulation suppressed cell proliferation, colony formation, cell migration, and invasion. Our data also indicated that tumor-suppressing role of TEKT4 knockdown in PTC cell lines was associated with the silence of the PI3K/Akt pathway. Our study revealed that TEKT4 shows important biological implications and is worthy of further study.     

鞘内注入醋酸泼尼松龙对大鼠镇痛作用及脊髓c-fos表达的影响

目的 :探讨鞘内注入泼尼松龙镇痛作用及其对脊髓c fos表达的影响与神经毒性作用。方法 :慢性鞘内置管的SD大鼠 2 4只 ,随机分为实验组 2 0只 ,对照组 4只。实验组又分成两个亚组 ,用药组 (EP组 ,n =10 ) ,生理盐水组 (EN组 ,n =10 ) ;对照组分为二个亚组 ,用药组 (CP组 ,n =2 ) ,空白对照组 (CE组 ,n =2 )。EP组经导管鞘内注入泼尼松龙 2mg/kg ,1小时后行福尔马林试验 ,进行行为学评分并计算痛级均数 ;2小时后灌注、固定 ,取脊髓腰膨大用ABC法行c fos免疫组化反应及病理检验 ,记数脊髓背角c fos阳性神经元数 ,并与鞘内注入等量生理盐水组 (EN )相比较。结果 :实验各组痛级均数比较有显著差异 (P <0 .0 5 ) ;脊髓腰膨大背角Ⅰ、Ⅱ层c fos阳性神经元数EP组有减少趋势 ,但无显著差异 ;腰膨大病理检验未示异常。结论 :鞘内注入泼尼松龙有镇痛作用 ,无神经毒性作用。     

Baicalin promotes apoptosis and inhibits proliferation and migration of hypoxia-induced pulmonary artery smooth muscle cells by up-regulating A2a receptor via the SDF-1/CXCR4 signaling pathway

Background

Baicalin is a flavonoid compound that exerts specific pharmacological effect in attenuating the proliferation, migration, and apoptotic resistance of hypoxia-induced pulmonary artery smooth muscle cells (PASMCs). However, the underlying mechanism has not been fully elucidated yet. Although our previous studies had indicated that activation of A2aR attenuates CXCR expression, little is known about the relationship between A2aR and SDF-1/CXCR4 axis in hypoxic PASMCs. In this study, we aimed to investigate the effect of A2aR on the SDF-1/CXCR4 axis in hypoxic PASMCs, the mechanism underlying this effect, and whether baicalin exerts its protective functions though A2aR.

Methods

Rat PASMCs were cultured under normoxia/hypoxia and divided into nine groups: normoxia, hypoxia, hypoxia + AMD3100 (a CXCR4 antagonist), hypoxia + baicalin, hypoxia + negative virus, normoxia + A2aR knockdown, hypoxia + A2aR knockdown, hypoxia + CGS21680 (an A2aR agonist), and hypoxia + A2aR knockdown + baicalin. Lentiviral transfection methods were used to establish the A2aR knockdown model in PASMCs. Cells were incubated under hypoxic conditions for 24 h. Expression levels of A2aR, SDF-1, and CXCR4 were detected using RT-qPCR and western blot. The proliferation and migration rate were observed via CCK-8 and Transwell methods. Cell cycle distribution and cell apoptosis were measured by flow cytometry (FCM) and the In-Situ Cell Death Detection kit (Fluorescein).

Results

Under hypoxic conditions, levels of A2aR, SDF-1, and CXCR4 were significantly increased compared to those under normoxia. The trend of SDF-1 and CXCR4 being inhibited when A2aR is up-regulated was more obvious in the baicalin intervention group. Baicalin directly enhanced A2aR expression, and A2aR knockdown weakened the function of baicalin. SDF-1 and CXCR4 expression levels were increased in the hypoxia + A2aR knockdown group, as were the proliferation and migration rates of PASMCs, while the apoptotic rate was decreased. Baicalin and CGS21680 showed opposite effects.

Conclusions

Our data indicate that baicalin efficiently attenuates hypoxia-induced PASMC proliferation, migration, and apoptotic resistance, as well as SDF-1 secretion, by up-regulating A2aR and down-regulating the SDF-1/CXCR4 axis.

     

双氢青蒿素对人骨肉瘤细胞TE85细胞内尿激酶型纤溶酶原激活物和色素上皮衍生因子表达的影响

目的 观察双氢青蒿素(DHA)对人骨肉瘤细胞活性、转移能力以及细胞中尿激酶型纤溶酶原激活物(uPA)和色素上皮衍生因子(PEDF)表达的影响.方法 将不同浓度的DHA(5、10、20、40、80 μmol/L)作用于体外培养的正常人成骨细胞和人骨肉瘤细胞TE85 12、24、48 h后,噻唑蓝(MTT)法测定DHA对细胞活性的影响,反转录-聚合酶链反应(RT-PCR)法检测细胞中uPA和PEDF mRNA水平的表达,Westen blot法检测uPA和PEDF蛋白水平的表达.结果 DHA对人成骨细胞活性无明显影响(P＞0.05).DHA能够明显抑制人骨肉瘤细胞TE85的活性(P＜0.05).不同作用时间下DHA对人骨肉瘤细胞TE85的半数抑制浓度(IC50)分别为(12 h)=(41.66±0.53) μmol/L、IC50(24 h)=(32.28 ±0.27)μmol/L和IC50 (48 h)=(22.53±1.26) μmol/L.DHA能够明显减少人骨肉瘤细胞的迁移和细胞中uPA的表达水平,同时细胞中PEDF表达升高(P＜0.05).结论 DHA对正常人体骨组织无害,能够有效抑制骨肉瘤细胞生长和转移.     

Blood–brain barrier dysfunction and myelin basic protein in survival of amyotrophic lateral sclerosis with or without frontotemporal dementia

Neurological Sciences - We aim to investigate blood–brain barrier (BBB) dysfunction and myelin basic protein (MBP) in amyotrophic lateral sclerosis (ALS) with or without frontotemporal...     

Side effects of long-term oral anti-seizure drugs on thyroid hormones in patients with epilepsy: a systematic review and network meta-analysis

Neurological Sciences - Anti-seizure drugs have long been known to affect thyroid hormone levels in epilepsy patients. The current study is a network meta-analysis designed to produce a systematic...