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Background: Minimal manifestation status (MMS) is an important landmark in the treatment of myasthenia gravis (MG), and predictors of MMS induction have rarely been identified in previous studies. Objective: The objective of this study is to evaluate the clinical factors associated with MMS induction among patients with MG. Design: This two-step retrospective cohort study with a single center investigated the factors that may be associated with MMS induction and retested these predictors in a test cohort. Methods: A total of 388 diagnosed MG patients who visited Xiangya Hospital between 1 July 2015 and 1 July 2019 were involved. We performed detailed chart reviews and recorded all cases achieving MMS. Demographics and clinical characteristics were also collected and their relationships to achieving MMS were investigated. Results: MMS was achieved in 124 patients (50.2%), and the median time to achieve MMS was 26months. Several factors were found to be associated with MMS induction in exploring cohort, including muscle-specific tyrosine-protein kinase receptor (MuSK) antibody positivity (adjusted hazard ratio, HR = 4.333, 95% confidence interval, CI: 1.862–10.082), isolated ocular involvement (adjusted HR = 1.95, 95% CI: 1.284–2.961), and low baseline quantitative myasthenia gravis score (QMG score; adjusted HR = 2.022, 95% CI: 1.086–3.764). These factors were then retested in the test cohort. Isolated ocular involvement or low baseline QMG scores were factors found to be beneficial for MMS induction were confirmed. Conclusion: Isolated ocular involvement and low baseline QMG score are predictors of MMS induction in MG patients. [ABSTRACT FROM AUTHOR]

Aim: The purpose of the present study was to explore the function and mechanism of tensin 1 (TNS1) in non-small cell lung cancer (NSCLC) progression. Methods: The expression of TNS1 in NSCLC cells and tissues was assessed by RT-PCR and Western blot. Besides, Kaplan-Meier survival analysis was recruited to explore the association between TNS1 and NSCLC. Cell growth was analyzed by MTT and flow cytometry assay, while cell metastasis was determined by wound healing and transwell assays. The targeting relationship between TNS1 and miR-152 was assessed by luciferase activity assays. And Western blot was employed to determine the expression of related proteins of Akt/mTOR/RhoA pathway. Results: TNS1 level was boosted in NSCLC cells and tissues, related to the prognosis of NSCLC patients. Furthermore, it was proved that TNS1 promoted the growth and metastasis of NSCLC cells via Akt/mTOR/RhoA pathway. And miR-152 targeted TNS1 to affect the progression of NSCLC. Conclusion: miR-152/TNS1 axis inhibits the progression of NSCLC by Akt/mTOR/RhoA pathway. [ABSTRACT FROM AUTHOR]

Purpose: The IL-2 gene polymorphisms have been reported to be associated with the development of autoimmune disease. However, there are no published studies examining the influence of the IL-2 gene polymorphisms on the response of myasthenia gravis (MG) patients to tacrolimus (Tac). The goal of this study was to investigate the relationship between the polymorphisms of IL-2 and Tac response in MG patients. Methods: Ninety-two MG patients treated with Tac were studied, including 57 Tac-effective patients and 35 Tac-ineffective patients. Then, we selected four single-nucleotide polymorphisms (SNPs: rs2069776, rs2069772, rs2069762, rs2069763) in the IL-2 gene. Next, we analyzed the distribution of genotypes, allelic frequencies of SNPs, and haplotype frequencies among polymorphisms in the two groups of patients. Results: The distribution of the allelic frequency of the rs2069762 variant differed between the Tac-effective and Tac-ineffective patients (P = 0.02). Genotypes G/T and G/G of rs2069762 were differently distributed between the two groups when the wild genotype T/T was assigned as a reference (P < 0.001 for G/T; P = 0.003 for G/G). Patients with the TAGG haplotype tended to be Tac-ineffective (P < 0.001, OR: 0.15, 95% CI: 0.05–0.43). Conclusion: Myasthenia gravis patients with the rs2069762 variant, rs2069762 G/T and G/G genotype, and TAGG haplotype for IL-2 tended to respond poorly to Tac treatment. [ABSTRACT FROM AUTHOR]

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. The results of the present study demonstrate that high expression of microRNA (miR)-137 and low expression of steroid receptor coactivator-3 (SRC3) had a significant negative correlation in 40 NSCLC tissue samples. In addition, cell colony formation and proliferation was significantly reduced in miR-137-transfected A549 and NCI-H838 cells compared with scramble-transfected NSCLC cell lines. miR-137 was identified to induce G1/S cell cycle arrest and dysregulate the mRNA expression of cell cycle-associated proteins (proliferating cell nuclear antigen, cyclin E, cyclin A1, cyclin A2 and p21) in NSCLC cells. Notably, miR-137 could significantly suppress SRC3 3' untranslated region (UTR) luciferase-reporter activity, an effect that was not detectable when the putative 3'-UTR target-site was mutated, further clarifying the molecular mechanisms underlying the role of miR-137 in NSCLC. In conclusion, the results of the present study suggest that miR-137 suppresses NSCLC cell proliferation by partially targeting SRC3. [ABSTRACT FROM AUTHOR]

The aim of the present study was to investigate the effects of human papillomavirus (HPV) infection on the gynecological disease of vaginitis and to demonstrate how the small interfering RNA (siRNA) method may be used for HPV prevention in the clinic. Human vaginal epithelial cells were transfected with HPV-11 L1 expression vector and siRNA-HPV-11 L1 vectors and a control group was transfected with scrambled siRNA. Cell proliferation in each group was analyzed using the MTT assay and the expression of apoptosis-associated proteins was measured by western blot analysis. Compared with the control group, HPV-11 L1 mRNA and protein levels were significantly increased following transfection with the HPV-11 L1 expression vector in cells (P<0.05), but this result was significantly reversed by silencing of HPV-11 L1 (P<0.05). In addition, cell proliferation in the HPV-11 group was lower than that in the control group; however, cell proliferation was signifi- cantly increased in cells transfected with silenced L1 compared with that in the control group (P<0.05). Furthermore, silencing of HPV-11 L1 significantly decreased caspase-3 and caspase-9 expressions in cells, whereas the expression was increased in the HPV-11 L1 group (P<0.05). The present study suggested that siRNA-mediated silencing of HPV-11 L1 may have potential therapeutic applications for treating gynecological diseases associated with HPV-11 infection. [ABSTRACT FROM AUTHOR]

In six sheep, radiopaque markers were placed on the left ventricle (LV), the mitral annulus, the left atrium (LA), and the central edge of both mitral leaflets to investigate the effects of acute LV ischemia on atrial contraction, mitral annular area (MAA), and mitral regurgitation (MR). Animals were studied with biplane videofluoroscopy and transesophageal echocardiography before and during balloon occlusion of the left anterior descending (LAD), distal circumflex (dLCX), and proximal circumflex (pLCX) coronary arteries. MAA and LA area were calculated from the corresponding markers. LAD occlusion did not alter LA area reduction or presystolic MAA reduction, whereas dLCX occlusion resulted in a mild decrease in the former with no change in the latter. Neither occlusion resulted in MR. pLCX occlusion, however, significantly decreased LA area and presystolic MAA reduction and resulted in increased end-diastolic MAA, delayed valve closure from end diastole, and MR. Decreased atrial contractile function, as observed during acute posterolateral ischemia, is linked to diminished presystolic mitral annular reduction, a larger mitral annular size at end diastole, and MR. [ABSTRACT FROM AUTHOR]

Maternal cigarette smoking is the single most widespread prenatal insult. Smoking has long been associated with adverse pregnancy outcomes, both for the mother, her fetus, and newborn. The present study was designed to test the hypothesis that fetal and neonatal nicotine exposure has adverse effects on coronary vasculature development, resulting in changes in coronary blood flow in adult offspring. Nicotine (2.1mg/d) was administered to pregnant rats via subcutaneous osmotic minipumps throughout gestation and up to 10 days after delivery. Hearts were isolated from 3 month-old male and female offspring, and were subjected to 25-min of ischemia followed by 60-rain of reperfusion in a Langendorff preparation. Pulmonary artery effluent was collected as an index of coronary flow (ml/min/g heart wet weight). Nicotine significantly decreased coronary flow in female (10.4±0.8 vs. 7.1±0.7, P<0.05) but not in male (9.1±0.5 vs. 9.0±0.7, P>0.05) hearts at baseline. Ischemia and reperfusion decreased coronary flow in both male and female hearts, with higher coronary flow in female hearts. Nicotine treatment significantly decreased coronary flow during reperfusion up to 60 min in female, but not in male, hearts. The results suggest that prenatal nicotine exposure selectively decreases coronary flow in adult female offspring. (Supported in part by NIH grant S06GM073842 and TRDRP Award # 14FT-0075) [ABSTRACT FROM AUTHOR]

Recent epidemiological studies have demonstrated that in utero exposure to maternal cigarette smoking is associated with cardiovascular diseases in offspring later in life. The present study tested the hypothesis that fetal and neonatal nicotine exposure increased heart susceptibility to ischemia/reperfusion (I/R) injury in adult offspring. Nicotine (2.1 mg/d) was administered to pregnant rats via subcutaneous osmotic minipumps throughout gestation and up to 10 days after delivery. Hearts were isolated from 3 month-old male and female offspring, and were subjected to 25-min of ischemia followed by 60-min of reperfusion in a Langendorff preparation. Cardiac functional parameters: heart rate, left ventricular developed pressure and end diastolic pressure, dP/dtmax, dP/dtmin, and left ventricular infarct size were measured. Pre-ischemic values of cardiac function were not significantly different between the control and nicotine-treated hearts in either male or female offspring. Prenatal nicotine exposure significantly increased I/R-induced infarct size in left ventricles, and significantly attenuated postischemic recovery of left ventricular function in both male and female offspring. However, the effect of nicotine was significantly more pronounced in females than males. The findings suggest that prenatal nicotine exposure causes a reprogramming of cardiac function resulting in an increase in heart susceptibility to I/R injury in adult offspring. In addition, the effect of nicotine shows a gender dichotomy with females being more susceptible than males. [ABSTRACT FROM AUTHOR]

Epidemiologic studies suggest that prenatal exposure to maternal cigarette smoking is associated with an increased risk of elevated blood pressure in postnatal life. The present study was designed to test the hypothesis that fetal and neonatal nicotine exposure increased vascular contractility in adult offspring. Nicotine was administered to pregnant rats via subcutaneous osmotic minipumps throughout gestation and up to 10 days after delivery. Aortas were isolated from 3 month-old male and female offspring. Nicotine significantly increased KCl- and NE-induced contractions in male, but not in female, arteries. Inhibition of eNOS with L-NNA significantly increased NE-induced contractions in control, but not in nicotine-treated, male arteries. In contrast, nicotine caused a significant increase in L-NNA-mediated potentiation of NE-induced contractions in female arteries. Nicotine had no effect on SNP-induced relaxations of aortas. However, it decreased endothelium-dependent relaxation induced by acetylcholine in male offspring, but increased it in females. There were no differences in eNOS protein levels in aortas between control and nicotine-treated animals. The results suggest that fetal and neonatal nicotine exposure alters vascular functions in adult offspring in a gender specific manner, which may lead to an increased risk of cardiovascular dysfunction in later life. [ABSTRACT FROM AUTHOR]

Studies in both humans and animals have demonstrated that nicotine impairs endothelium-dependent relaxation of arterioles. It has been suggested that plasma levels of nitric oxide are decreased following the infusion of nicotine. The present study tested the hypothesis that nicotine has direct effects on endothelial cells and causes decreases in intracellular Ca2+ concentrations and nitric oxide release. Bovine coronary artery endothelial cells at the fifth passage were cultured to 80% confluence. For the time course study, cells were treated with 10 µM nicotine from 5 min to 48 h. To determine the dose-response, cells were treated with 0.01 - 30 µM nicotine for 24 h. Intracellular Ca2+ concentrations were measured with cells loaded with fura-2. Nitric oxide in culture medium was measured by the chemiluminescence method. Short-term nicotine treatment up to 60 min showed no effect on intracellular Ca2+ concentrations and nitric oxide release. However, nicotine treatment for 24 h inhibited ATP-induced increases in intracellular Ca2+ concentrations and significantly decreased the maximal Ca2+ response from 187.4±13.2 to 115.0±7.3 nM. In accordance, nicotine treatment had no effect on nitric oxide release until 24 h. At 24 h treatment, nicotine (0.01 to 30 µM) produced dose-dependent decreases in nitric oxide release. The results suggest that chronic nicotine exposure decreases intracellular Ca2+ concentrations and nitric oxide release in cultured coronary artery endothelial cells. [ABSTRACT FROM AUTHOR]

Cigarette smoking increases coronary vascular resistance, impairs coronary flow-mediated dilation, and is a major risk factor for coronary heart disease. Out of over 4000 individual compounds contained in tobacco smoke, nicotine is one of the most important ones in related to coronary heart disease. The present study tested the hypothesis that prenatal nicotine exposure decreases coronary nitric oxide release in adult offspring. Nicotine (2.1 mg/d) was administered to pregnant rats via subcutaneous osmotic minipumps throughout gestation and up to 10 days after delivery. Hearts were isolated from 3 month-old male and female offspring, and were subjected to 25-rain of ischemia followed by 60-min of reperfusion in a Langendorff preparation. Nitric oxide (nmols/min/g heart wet weight) in coronary effluent was measured by the chemiluminescence method. Nicotine significantly decreased coronary nitric oxide release in male (4.9±0.8 vs. 2.8±0.4, P<0.05) but not in female (3.3±1.0 vs. 1.8±0.5, P>0.05) hearts at baseline. Ischemia and reperfusion decreased coronary nitric oxide release in both male and female hearts, with higher nitric oxide levels in male hearts. Nicotine treatment significantly decreased coronary nitric oxide release during reperfusion up to 60 min in male, but not in female, hearts. These findings suggest that prenatal nicotine exposure selectively decreases coronary nitric oxide release in adult male offspring, which may lead to a change in coronary blood flow. [ABSTRACT FROM AUTHOR]