Pretreatment controlling nutritional status (CONUT) score and carcinoembryonic antigen level provide tumor progression and prognostic information in gastric cancer: A retrospective study.

This study explores the role of combining the controlling nutritional status (CONUT) score and the carcinoembryonic antigen (CEA) level on predicting tumor stage and prognosis in gastric cancer (GC) patients. A total of 682 GC patients were included in this retrospective study. CONUT scores and CEA levels were combined to establish a new scoring system: CONUT-CEA score. cutoff values for distinguishing patients between stage IV and non-stage IV were established by receiver operating characteristic curves. cutoff values for predicting prognosis were determined by maximum χ2 method. The CONUT and CEA cutoff values for discriminating stage IV patients from non-stage IV patients were 2.0 and 5.58 ng/mL, respectively. Logistic regression model demonstrated that high CONUT-CEA score was related to advanced tumor stage. Among non-stage IV patients, CONUT and CEA cutoff values of 2.0 and 9.50 ng/mL predicted overall survival (OS), respectively. The Cox proportional risk model revealed that high CONUT-CEA score was notable related to decreased OS (2 vs 0: hazard ratios (HR) = 2.358, 95% confidence intervals (CI) = 1.412-3.940, P = .001) and decreased disease-free survival (2 vs 0: HR = 1.980, 95% CI = 1.072-3.656, P = .003). The CONUT-CEA score may be a good biomarker for predicting tumor stage and prognosis in GC patients.

Enhanced CT-guided adrenal venous sampling versus traditional X-ray-guided adrenal venous sampling in patients with primary aldosteronism.

To compare the accuracy, safety, operation time, and radiation dose of enhanced computed tomography (CT)-guided adrenal vein sampling (AVS) versus traditional X-ray-guided AVS in patients with primary aldosteronism. A total of 97 patients with primary aldosteronism were randomly assigned to either the enhanced CT-guided group (n = 48) or the traditional X-ray-guided group (n = 49). Baseline characteristics were compared between the 2 groups. The primary outcome was the accuracy of AVS, assessed by aldosterone-to-cortisol ratio. Secondary outcomes included safety measures (intraoperative and postoperative complication rates, procedure termination rates, blood pressure, and heart rate changes), operation time, and radiation dose. The CT-guided group demonstrated significantly higher aldosterone-to-cortisol ratios, indicating improved accuracy in AVS (P < .001). The CT-guided group also showed significantly lower intraoperative blood pressure change and intraoperative heart rate change compared to the X-ray-guided group (P < .05). In addition, the CT-guided group had significantly shorter operation times (P < .001) and lower radiation exposure (P < .001). The enhanced CT-guided AVS demonstrated significantly better accuracy, safety, and efficiency compared to traditional X-ray-guided AVS in patients with primary aldosteronism. The enhanced CT-guided approach also resulted in lower radiation exposure for patients, making it a favorable option in the diagnosis and treatment of primary aldosteronism.

Impact of metacognition on attitudes toward epilepsy in medical students.

PURPOSE: This study evaluated medical students' knowledge and attitudes toward epilepsy and the influence of metacognition thereon. METHOD: Valid questionnaires were administered to medical students including undergraduate, professional postgraduate, and standardized residency training students (N = 503). The questionnaire had 4 parts: demographic information, knowledge of epilepsy, attitudes toward epilepsy, and metacognitive assessment. The Chinese Public Attitudes Toward Epilepsy scale and 30-Item Metacognition Questionnaire were used to assess attitudes and metacognition, respectively. RESULTS: Almost all participants had heard of epilepsy; 38.8% had witnessed a seizure and 25% were acquainted with a person with epilepsy. The proportion of correct answers to epilepsy-related knowledge ranged from 40.6% (Putting an object into the mouth of a person experiencing an epileptic seizure) to 97% (Convulsion is a symptom of epilepsy). However, knowledge of epilepsy was not able to affect attitudes toward epilepsy. Age, years of clinical experience, having witnessed a seizure, positive belief of worry, and need to control thinking were correlated with the different domains of attitude toward epilepsy. When participants were divided into 2 groups-i.e., those with high and low knowledge of epilepsy, participants in the former group who had a positive belief of worry or had not witnessed any seizures were more likely to have negative attitudes toward epilepsy. CONCLUSION: Medical students showed good awareness of the etiology and symptoms of epilepsy. Overall, attitudes toward epilepsy were negative. A positive belief of worry was associated with a more negative attitude toward epilepsy among respondents with greater knowledge of epilepsy.

Comparative genetic and epigenetic of the Sphagneticola trilobata (L.) Pruski from different regions in China.

BACKGROUND: Sphagneticola trilobata (L.) Pruski is a prevalent and widely distributed invasive plant in South China. To investigate the molecular mechanisms underlying its rapid adaptation, we employed DNA methylation-sensitive amplified polymorphism (MSAP) and simple sequence repeat (SSR) analysis to study 60 S. trilobata individuals collected from Fuzhou (FZ), Haikou (HK), Jinghong (JH) and Guangzhou (GZ). RESULTS: In this study, we computed the Shannon diversity index (I) of SSR and MSAP as 0.354 and 0.303, respectively. The UPGMA phylogenetic tree and PCoA analyses showed that MSAP had a better discriminatory power to distinguish populations from different regions. Notably, the GZ population was found to be the most distinct from the other three populations. Moreover, Mantel analysis revealed a significantly higher correlation between epigenetic distance and geographic distance as compared to genetic distance and geographic distance. Consequently, the correlation between epigenetic distance and geographic distance observed to be markedly stronger than that between genetic distance and geographical distance on Mantel analysis. CONCLUSIONS: The S. trilobata populations in various regions displayed a high of complementary genetic and epigenetic diversity, which was a key feature contributing to their rapid invasion. Interestingly, the correlation between epigenetics and geographical distance was significantly stronger than that observed for genetics and geographical distance. These findings indicated that the epigenetic mechanism of S. trilobar exhibited high plasticity, leading to significant differences in methylation pattern across different populations.

The Value of Python Programming in General Education and Comprehensive Quality Improvement of Medical Students Based on a Retrospective Cohort Study.

Objective: A retrospective cohort study was conducted to analyze the application value of Python programming in general education and comprehensive quality improvement of medical students. Methods: A retrospective analysis was made on the application value of Python programming in the general education classroom of medical students from September 2020 to July 2021 by undergraduate students majoring in anesthesia in grade 2020, imaging in grade 2019, clinical in grade 2020, and laboratory sciences in grade 2020 in our university. A hundred students who used Python programming in general education class were divided into study group and control group. The teaching satisfaction, medical knowledge and lifelong learning ability, clinical skills, medical service ability, disease prevention, health promotion ability, interpersonal communication ability, and information management and research ability were compared between the two groups. Results: In a comparison of teaching satisfaction between the two groups, the study group was very satisfied in 89 cases, satisfactory in 10 cases, and general in 1 case, and the satisfaction rate was 100.00%; the control group was very satisfied in 54 cases, satisfactory in 23 cases, general in 13 cases, and dissatisfied in 10 cases, and the satisfaction rate was 90.00%. The teaching satisfaction in the study group was higher than that in the control group, and the difference was statistically significant (P < 0.05). Compared with the control group, medical knowledge ability (basic knowledge, general education, and professional knowledge) and lifelong learning ability (learning concept and professional learning attitude) in the research group were significantly higher than those in the research group (P < 0.05). The scores of clinical skills (medical history analysis, basic diagnosis, treatment techniques, and disease analysis) and medical service ability (first aid ability, comprehensive analysis ability, and disease analysis ability) in the study group were significantly higher than those in the control group (P < 0.05). In terms of the ability of disease prevention and health promotion, the scores of disease prevention (health guidance, health education, and self-care) and health promotion ability (cooperative participation in diagnosis and treatment, guidance of medical and health work, and rational use of health resources) in the study group were higher than those in the control group, and the difference was statistically significant (P < 0.05). In the comparison of interpersonal communication ability, the scores of listening, expression, understanding, trust, medical terminology, and communication ability in the study group were higher than those in the control group, and the difference was statistically significant (P < 0.05). Comparing information management with research ability, the scores of information management ability (searching information, screening information, and sorting information) and research ability (arrangement ability, planning ability, and execution ability) in the research group were higher than those in the control group, and the data difference was statistically significant (P < 0.05). Conclusion: The application of the Python programming method in general education and comprehensive quality improvement of medical students can effectively improve medical students' teaching satisfaction and medical knowledge such as lifelong learning ability, clinical skills, medical service ability, disease prevention, health promotion ability, interpersonal communication ability, and information management and research ability, which has a positive impact on the improvement of comprehensive quality.

A RFID Authentication Protocol for Epidemic Prevention and Epidemic Emergency Management Systems.

The outbreak of the novel coronavirus has exposed many problems in the auxiliary information system for epidemic prevention and control, which needs to be resolved by using methods such as the antitampering of logistics data and the management and control of epidemic materials. This article discusses the introduction of emerging technologies such as Radio Frequency Identification (RFID), which support privacy protection into the auxiliary information system for epidemic prevention and control. Recently, this paper found that Khwaja et al.'s protocol (RAPUS protocol) is susceptible to database impersonation attacks and reader impersonation attacks. Therefore, this article proposes the enhanced protocol, which not only perfectly solves the problems of the abovementioned protocols but also comprehensively compares multiple protocols. The enhanced protocol has higher efficiency and security. The security of the proposed protocol (RAPUS + protocol) is analyzed by GNY logic and the AVISPA model. The designed scheme can help realize the safety and traceability of epidemic prevention materials and improve the automation and decision-making efficiency of the epidemic prevention.

Impact of violent video games and other factors on aggressive behavior of junior high school students in Shanghai / 中国学校卫生

Objective@#To understand the impact of violent video games exposure, self control level and coping style on aggressive behavior of junior high school students in Shanghai, and provide a basis for future interventions to effectively reduce adolescents aggressive behavior.@*Methods@#Cluster sampling was used to select 1 886 students of 4 public middle schools in Shanghai from May to June 2019. The data was collected included Violent Video Game Use Habits Questionnaire, Buss & Perry aggression questionnaire, Adolescent Self Control Dual System Scale and Simple Coping Style Questionnaire.@*Results@#According to the potential profile analysis, the level of aggressive behavior of junior school students in Shanghai could be divided into four groups, which was low aggressive group，middle aggressive group one, middle aggressive group two and high aggressive group according to level of aggregate. After controlling for gender and age, multivariate Logistic regression showed that exposure to violent video games, impulse system and negative response were risk factors for aggressive behavior( P <0.05); using low aggressive group as control group，the OR of violent video games in other three groups were 1.26, 1.30 and 1.70 respectively. The OR of impulse system were 2.96 , 4.40 and 6.84 respectively. The OR of negative response were 1.17, 1.42 and 1.74 respectively. Positive response was a protective factor( P <0.05). Using low aggressive group as control group, the OR of positive in other three groups were 0.82, 0.52 and 0.49 respectively.@*Conclusion@#Violent video game exposure, impulsive system and negative coping style can increase the level of aggressive behavior of junior high school students, while positive coping style can reduce the level of aggression of junior middle school students.

Beneficial effects of cysteamine in Thy1-α-Syn mice and induced pluripotent stem cells with a SNCA gene triplication.

A number of publications have reported that cysteamine has significant therapeutic effects on several aspects of Parkinson's disease (PD)-related pathology but none of these studies have evaluated its impact on pathological forms of α-Synuclein (α-Syn), one of the main hallmarks of PD. We therefore tested the efficacy of cysteamine on the Thy1-α-Syn mouse model which over-expresses full-length human wild-type α-Syn. Two-month (early stage disease) and 6-month old (late stage disease) mice and littermate controls were treated daily with cysteamine (20 mg/kg, i.p.) to assess the protective and restorative properties of this compound. After 6 weeks of treatment, animals were tested using a battery of motor tests. Cysteamine-treated transgenic mice displayed significant improvements in motor performance as compared to saline-treated transgenic littermates. Post-mortem readouts revealed a reduction in fibrillation, phosphorylation and total levels of overexpresed human α-Syn. To determine if such outcomes extended to human cells, the benefits of cysteamine were additionally tested using 6-hydroxydopamine (6-OHDA) treated neurons differentiated from induced pluripotent stem cells (iPSCs) derived from a PD patient harbouring a triplication of the SNCA gene. SNCA neurons treated with cysteamine exhibited significantly more intact/healthy neurites than cells treated with 6-OHDA alone. Additionally, SNCA neurons treated with cysteamine in the absence of 6-OHDA showed a trend towards lower total α-Syn levels. Overall, our in vivo and in vitro findings suggest that cysteamine can act as a disease-modifying molecule by enhancing -the survival of dopaminergic neurons and reducing pathological forms of α-Syn.

Liraglutide suppresses production of extracellular matrix proteins and ameliorates renal injury of diabetic nephropathy by enhancing Wnt/ß-catenin signaling.

The Wnt/ß-catenin signaling pathway is involved in production of the extracellular matrix (ECM) by mesangial cells (MCs). Recent studies by us and others have demonstrated that glucagon-like peptide-1 receptor agonists (GLP-1RAs) have protective effects against diabetic nephropathy. The purpose of the present study was to investigate whether the Wnt/ß-catenin signaling in MCs contributes to GLP-1RA-induced inhibition of ECM accumulation and mitigation of glomerular injury in diabetic nephropathy. In cultured human mesangial cells, liraglutide (a GLP-1RA) treatment significantly reduced high glucose (HG)-stimulated production of fibronectin, collagen type IV, and α-smooth muscle actin, and the liraglutide effects were significantly attenuated by XAV-939, a selective inhibitor of Wnt/ß-catenin signaling. Furthermore, HG treatment significantly decreased protein abundance of Wnt4, Wnt5a, phospho-glycogen synthase kinase-3ß, and ß-catenin. These HG effects on Wnt/ß-catenin signaling proteins were significantly blunted by liraglutide treatment. For in vivo experiments, we administered liraglutide (200 µg·kg-1·12 h-1) by subcutaneous injection to streptozocin-induced type 1 diabetic rats for 8 wk. Administration of liraglutide significantly improved elevated blood urine nitrogen, serum creatinine, and urinary albumin excretion rate and alleviated renal hypertrophy, mesangial expansion, and glomerular fibrosis in type 1 diabetic rats, whereas blood glucose level and body weight did not have significant changes. Consistent with the in vitro experiments, liraglutide treatment significantly reduced the diabetes-induced increases in glomerular fibronectin, collagen type IV, and α-smooth muscle actin and decreases in glomerular Wnt/ß-catenin signaling proteins. These results suggest that liraglutide alleviated glomerular ECM accumulation and renal injury in diabetic nephropathy by enhancing Wnt/ß-catenin signaling.

Prognostic significance of high triglyceride and apolipoprotein B levels in patients with stage III and high-risk stage II colorectal cancer undergoing curative surgery.

Although epidemiologic studies suggest that dyslipidemia increases the risk of colorectal cancer (CRC), the prognostic value of blood lipid and apolipoprotein levels in CRC remains unclear. The aim of the present study was to investigate the impact of blood lipid and apolipoprotein levels on the prognosis of patients with stage III and high-risk stage II CRC undergoing curative surgery. Preoperative levels of total cholesterol, triglycerides (TG), high-density lipoprotein, low-density lipoprotein, very-low-density lipoprotein, apolipoprotein A1 and apolipoprotein B (APO-B) in patients with CRC undergoing surgery were evaluated. The cut-off values of these factors were determined by the maximal x2 method and were used to classify patients into two prognostic groups: Poor and good prognosis groups. The patients prognostic values were assessed using the Kaplan-Meier curve and Cox regression analysis. In addition, the impact of these parameters on the prognosis and their predictive accuracy were evaluated using nomograms and Harrells concordance index, respectively. In total, 246 patients were included in this evaluation. Based on the cut-off points for TG (1.53 mmol/l in men and 1.58 mmol/l in women) and APO-B (0.73 mmol/l in men and women), the present study determined that both TG and APO-B were predictors of disease-free survival (DFS) and overall survival (OS). Multivariate analysis demonstrated that high TG (men, ≥1.53 mmol/l; women, ≥1.58 mmol/l) and high APO-B (≥0.73 mmol/l) levels were significantly associated with decreased DFS and OS. Nomograms that included values for TG and APO-B levels demonstrated higher predictive accuracy compared with that of nomograms without these values. These results indicated that TG and APO-B levels may be good independent prognostic biomarkers after radical CRC surgery. Therefore, adjusting these parameters to moderate levels may be beneficial.

Merging RFID and Blockchain Technologies to Accelerate Big Data Medical Research Based on Physiological Signals.

The proliferation of physiological signals acquisition and monitoring system, has led to an explosion in physiological signals data. Additionally, RFID systems, blockchain technologies, and the fog computing mechanisms have significantly increased the availability of physiological signal information through big data research. The driver for the development of hybrid systems is the continuing effort in making health-care services more efficient and sustainable. Implantable medical devices (IMD) are therapeutic devices that are surgically implanted into patients' body to continuously monitor their physiological parameters. Patients treat cardiac arrhythmia due to IMD therapeutic and life-saving benefits. We focus on hybrid systems developed for patient physiological signals for collection, storage protection, and monitoring in critical care and clinical practice. In order to provide medical data privacy protection and medical decision support, the hybrid systems are presented, and RFID, blockchain, and big data technologies are used to analyse physiological signals.

Chrysin Alleviates Monocrotaline-Induced Pulmonary Hypertension in Rats Through Regulation of Intracellular Calcium Homeostasis in Pulmonary Arterial Smooth Muscle Cells.

Chrysin (CH) is the main ingredient of many medicinal plants. Our previous study showed that CH could suppress hypoxia-induced pulmonary arterial smooth muscle cells proliferation and alleviate chronic hypoxia-induced pulmonary hypertension by targeting store-operated Ca entry (SOCE)-[Ca]i pathway. In this study, we investigated the effect of CH on monocrotaline-induced pulmonary hypertension (MCTPH) and the mechanism behind it. Results show that, in MCTPH model rats, (1) CH significantly reduced the enhancement of right ventricular pressure, right ventricular hypertrophy, and pulmonary vascular remodeling; (2) CH markedly suppressed the promotion of SOCE and [Ca]i in pulmonary arterial smooth muscle cells; and (3) CH obviously inhibited the MCT-upregulated proliferating cell nuclear antigen, TRPC1, TRPC4, and TRPC6 expression in distal pulmonary arteries. These results demonstrate that CH likely alleviates MCTPH by targeting TRPC1,4,6-SOCE-[Ca]i pathway.

Tetramethylpyrazine: A promising drug for the treatment of pulmonary hypertension.

BACKGROUND AND PURPOSE: Tetramethylpyrazine (TMP) was originally isolated from the traditional Chinese herb ligusticum and the fermented Japanese food natto and has since been synthesized. TMP has a long history of beneficial effects in the treatment of many cardiovascular diseases. Here we have evaluated the therapeutic effects of TMP on pulmonary hypertension (PH) in animal models and in patients with pulmonary arterial hypertension (PAH) or chronic thromboembolic pulmonary hypertension (CTEPH). EXPERIMENTAL APPROACH: Three well-defined models of PH -chronic hypoxia (10% O2 )-induced PH (HPH), monocrotaline-induced PH (MCT-PH) and Sugen 5416/hypoxia-induced PH (SuHx-PH) - were used in Sprague-Dawley rats, and assessed by echocardiography, along with haemodynamic and histological techniques. Primary cultures of rat distal pulmonary arterial smooth muscle cells (PASMCs) were used to study intracellular calcium levels. Western blots and RT-qPCR assays were also used. In the clinical cohort, patients with PAH or CTEPH were recruited. The effects of TMP were evaluated in all systems. KEY RESULTS: TMP (100 mg·kg-1 ·day-1 ) prevented rats from developing experimental PH and ameliorated three models of established PH: HPH, MCT-PH and SuHx-PH. The therapeutic effects of TMP were accompanied by inhibition of intracellular calcium homeostasis in PASMCs. In a small cohort of patients with PAH or CTEPH, oral administration of TMP (100 mg, t.i.d. for 16 weeks) increased the 6-min walk distance and improved the 1-min heart rate recovery. CONCLUSION AND IMPLICATIONS: Our results suggest that TMP is a novel and inexpensive medication for treatment of PH. Clinical trial is registered with www.chictr.org.cn (ChiCTR-IPR-14005379).

Structure and Evolution of Glycogen Branching Enzyme N-Termini From Bacteria.

In bacteria, glycogen plays important roles in carbon and energy storage. Its structure has recently been linked with bacterial environmental durability. Among the essential genes for bacterial glycogen metabolism, the glgB-encoded branching enzyme GBE plays an essential role in forming α-1,6-glycosidic branching points, and determines the unique branching patterns in glycogen. Previously, evolutionary analysis of a small sets of GBEs based on their N-terminal domain organization revealed that two types of GBEs might exist: (1) Type 1 GBE with both N1 and N2 (also known as CBM48) domains and (2) Type 2 GBE with only the N2 domain. In this study, we initially analyzed N-terminal domains of 169 manually reviewed bacterial GBEs based on hidden Markov models. A previously unreported group of GBEs (Type 3) with around 100 amino acids ahead of the N1 domains was identified. Phylogenetic analysis found clustered patterns of GBE types in certain bacterial phyla, with the shorter, Type 2 GBEs predominantly found in Gram-positive species, while the longer Type 1 GBEs are found in Gram-negative species. Several in vitro studies have linked N1 domain with transfer of short oligosaccharide chains during glycogen formation, which could lead to small and compact glycogen structures. Compact glycogen degrades more slowly and, as a result, may serve as a durable energy reserve, contributing to the enhanced environmental persistence for bacteria. We were therefore interested in classifying GBEs based on their N-terminal domain via large-scale sequence analysis. In addition, we set to understand the evolutionary patterns of different GBEs through phylogenetic analysis at species and sequence levels. Three-dimensional modeling of GBE N-termini was also performed for structural comparisons. A further study of 9,387 GBE sequences identified 147 GBEs that might belong to a possibly novel group of Type 3 GBE, most of which fall into the phylum of Actinobacteria. We also attempted to correlate glycogen average chain length (ACL) with GBE types. However, no significant conclusions were drawn due to limited data availability. In sum, our study systematically investigated bacterial GBEs in terms of domain organizations from evolutionary point of view, which provides guidance for further experimental study of GBE N-terminal functions in glycogen structure and bacterial physiology.

Attenuation of acute lung injury in a rat model by Semen Cassiae.

BACKGROUND: Acute lung injury (ALI) is an inflammatory disorder. Semen Cassiae has potent anti-inflammatory activities. The aim of our study was to investigate whether Semen Cassiae plays a protective effect on lipopolysaccharide (LPS)-induced ALI and, if so, to elucidate its potential mechanism. METHODS: Male Sprague-Dawley rat lungs were injured by intratracheal instillation of LPS. Rats were treated with Semen Cassiae or vehicle 3 h after LPS challenge. Samples were harvested 24 h post-LPS administration. We also investigated the effects of Semen Cassiae on LPS stimulation in RAW 264.7 cells. RESULTS: LPS administration markedly induced pulmonary edema and polymorphonuclear neutrophil influxes. These changes were significantly attenuated in Semen Cassiae treated group. Moreover, Semen Cassiae markedly reduced pulmonary interleukin (IL)-6, tumor necrosis factor (TNF)-α, and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels. The pulmonary soluble epoxide hydrolase (sEH) activity and the DNA binding activity of Nuclear factor (NF)-κB were significantly inhibited in Semen Cassiae treated group. Furthermore, Semen Cassiae treatment significantly increased epoxyeicosatrienoic acids (EETs), and heme oxygenase-1 (HO-1) activity. Our in vitro study demonstrates that Semen Cassiae treatment may inhibit LPS induced IκBα phosphorylation and NF-κB p65 nucleus translocation. CONCLUSION: Semen Cassiae protects LPS-induced ALI in rats. Semen Cassiae can be developed as a novel treatment for ALI.

[Hypoxia induced the remodeling of pulmonary vein smooth muscle and reduced peroxisome proliferator activated receptor γ expression].

OBJECTIVE: To investigate the effect of chronic hypoxia on pulmonary vein remodeling in rats and its underlying molecular mechanism. METHODS: Totally 20 adult SD rats (200-250 g), in accordance with a random number table, were divided into normoxia control group (NC) and chronic hypoxia group (CH). CH group rats were put into automatic hypoxia box for 21 days. After that, RVSP, mRVP and RV/( LV+S) were measured; Lung histopathological sections were prepared. The lumen area, ratio of wall thickness to radius of pulmonary veins were gauged by using the Image Pro Plus 6.0 software. Primary PVSMCs were cultured in hypoxia (4% O2) or normoxia (21% O2) for 60 hours respectively before extracted total protein for Western blotting analysis. PPARγ protein expression in rat pulmonary vein smooth muscle and pulmonary vein smooth muscle cells was detected by Western blot. RESULTS: Compared with NC group [(27.06 ± 2.10), (12.58 ± 0.82) mmHg (1 mmHg=0.133 kPa)], the RVSP and mRVP in CH group [(50.46 ± 9.51), (21.66 ± 1.85)mmHg] were significantly increased (P<0.05). The RV/(LV+S) of CH group was (0.56 ± 0.05), markedly higher than that of NC group (0.36 ± 0.04, P<0.05). The luminal area/total area of vein in CH group decreased to (48.62 ± 13.61)% compared with that in NC group (66.16 ± 8.72)% (P<0.05). The wall thickness/venous radius (WT%) of CH group increased from (7.23 ± 0.71)% (NC) to (16.43 ± 5.08)% (P<0.05). The level of PPARγ protein in pulmonary vein smooth muscle of CH group was (52.95 ± 3.83)%, lower than that of NC (100 ± 0)% (P<0.05). PPARγ protein in pulmonary vein smooth muscle cells cultured in vitro in hypoxia was (59.38 ± 17.12)%, lower than that cultured in normoxia (100 ± 0)% (P<0.05). CONCLUSION: Hypoxia induced increase of RVSP, mRVP, RV/(LV+S), and accompanied with pulmonary venous remodeling. The underlying mechanism of the vein change may related to down-regulated expression of PPARγ.

Peroxisome proliferator-activated receptor γ inhibits pulmonary hypertension targeting store-operated calcium entry.

UNLABELLED: In this study, we investigated the role of peroxisome proliferator-activated receptor γ (PPARγ) on store-operated calcium entry (SOCE) and expression of the main store-operated calcium channel (SOCCs) components, canonical transient receptor potential (TRPC) in chronic hypoxia (CH)-induced pulmonary hypertension (CHPH) rat models. Small interfering RNA (siRNA) knockdown and adenoviral overexpression strategies were constructed for loss-of-function and gain-of-function experiments. PPARγ agonist rosiglitazone attenuates the pathogenesis of CHPH and suppresses Hif-1α, TRPC1, TRPC6 expression in the distal pulmonary arteries (PA), and SOCE in freshly isolated rat distal pulmonary arterial smooth muscle cells (PASMCs). By comprehensive use of knockdown and overexpression studies, and bioinformatical analysis of the TRPC gene promoter and luciferase reporter assay, we demonstrated that PPARγ exerts roles of anti-proliferation, anti-migration, and pro-apoptosis in PASMCs, likely by inhibiting the elevated SOCE and TRPC expression. These effects were inhibited under the conditions of hypoxia or Hif-1α accumulation. We also found that under hypoxia, accumulated Hif-1α protein acts as upstream of suppressed PPARγ level; however, targeted PPARγ rescue acts as negative feedback on suppressing Hif-1α level and Hif-1α mediated signaling pathway. PPARγ inhibits CHPH by targeting SOCE and TRPC via inhibiting Hif-1α expression and signaling transduction. KEY MESSAGES: Rosiglitazone protects PH by normalizing RVSP but not right ventricle hypotrophy. PPARγ inhibits PASMCs proliferation via targeting SOCE and TRPC by suppressing Hif-1α. PPARγ and Hif-1α share mutual inhibitory regulation in PASMCs. PPARγ restoration might be a beneficial strategy for PH treatment.

NOX4 mediates BMP4-induced upregulation of TRPC1 and 6 protein expressions in distal pulmonary arterial smooth muscle cells.

RATIONALE: Our previous studies demonstrated that bone morphogenetic protein 4 (BMP4) mediated, elevated expression of canonical transient receptor potential (TRPC) largely accounts for the enhanced proliferation in pulmonary arterial smooth muscle cells (PASMCs). In the present study, we sought to determine the signaling pathway through which BMP4 up-regulates TRPC expression. METHODS: We employed recombinant human BMP4 (rhBMP4) to determine the effects of BMP4 on NADPH oxidase 4 (NOX4) and reactive oxygen species (ROS) production in rat distal PASMCs. We also designed small interfering RNA targeting NOX4 (siNOX4) and detected whether NOX4 knockdown affects rhBMP4-induced ROS, TRPC1 and 6 expression, cell proliferation and intracellular Ca2+ determination in PASMCs. RESULTS: In rhBMP4 treated rat distal PASMCs, NOX4 expression was (226.73±11.13) %, and the mean ROS level was (123.65±1.62) % of that in untreated control cell. siNOX4 transfection significantly reduced rhBMP4-induced elevation of the mean ROS level in PASMCs. Moreover, siNOX4 transfection markedly reduced rhBMP4-induced elevation of TRPC1 and 6 proteins, basal [Ca2+]i and SOCE. Furthermore, compared with control group (0.21±0.001), the proliferation of rhBMP4 treated cells was significantly enhanced (0.41±0.001) (P<0.01). However, such increase was attenuated by knockdown of NOX4. Moreover, external ROS (H2O2 100 µM, 24 h) rescued the effects of NOX4 knockdown, which included the declining of TRPC1 and 6 expression, basal intracellular calcium concentration ([Ca2+]i) and store-operated calcium entry (SOCE), suggesting that NOX4 plays as an important mediator in BMP4-induced proliferation and intracellular calcium homeostasis. CONCLUSION: These results suggest that BMP4 may increase ROS level, enhance TRPC1 and 6 expression and proliferation by up-regulating NOX4 expression in PASMCs.

[Tanshinone IIA sulfonate upregulated pulmonary artery smooth muscle peroxisome proliferator-activated receptor γ expression in monocrotaline induced pulmonary hypertension rat].

OBJECTIVE: To investigate the effect of sodium tanshinone IIA sulfonate (STS) on rat right ventricular systolic pressure (RVSP), mean right ventricular pressure (MRVP), right ventricular hypertrophy index [RV/(LV+S)], pulmonary vascular remodeling, and PPARγ protein expression in pulmonary artery smooth muscle of monocrotaline (MCT) induced rat pulmonary hypertension model. METHODS: The pulmonary hypertension model was established by subcutaneously injection of MCT, and the rats were treated with or without STS for 21 days. After that, RVSP, mRVP and RV/(LV+S) were measured. Lung histopathological sections were prepared, and the lumen area, the wall thickness and arterial radius of pulmonary arteries were quantified using the Image Pro Plus 6.0 software. PPARγ protein expression in rat pulmonary artery smooth muscle was detected by Western blot. RESULTS: Compared with control group, the RVSP, mRVP were significantly increased in MCT group (P < 0.05), while in the MCT+STS group, it was decreased from (81.2 ± 1.9) and (28.6 ± 2.0) mmHg to (35.4 ± 8.3) and (14.1 ± 5.4) mmHg, respectively (P < 0.05). The RV/(LV+S) of MCT group was (0.57 ± 0.04), markedly higher than those of control group and control+STS group (0.33 ± 0.02) and (0.34 ± 0.02) , respectively, P < 0.05, while in MCT+STS group, the RV/(LV+S) was (0.43 ± 0.02), lower than that of MCT group (P < 0.05) ;The luminal area/total area of MCT group decreased to (27 ± 6)%compared with control rats (56.00 ± 3.00) % (P < 0.05) . The wall thickness/artery radius (WT%) of MCT group increased from (20 ± 4) % (control group) to (40 ± 3) % (P < 0.05) .In MCT+STS treated rats, luminal area/ total area and WT% were (39.0 ± 2.0) %and (31.0 ± 2.0) %, both statistically different from MCT group (P < 0.05) . The level of PPARγ protein in pulmonary artery smooth muscle of MCT group was (48 ± 4) %, lower than control group (100 ± 0) % (P < 0.05) .In the MCT+STS group, PPARγ protein expression was recovered (102 ± 3) %, (P < 0.05) . CONCLUSION: STS markedly decreased RVSP,MRVP, RV/(LV+S) and pulmonary vascular remodeling in MCT induced pulmonary hypertension rat, and PPARγ might be targeted as a key molecule during STS treatment.

Antitumor effect of para-toluenesulfonamide against lung cancer xenograft in a mouse model.

BACKGROUND: Conventional chemotherapy and radiation therapy against non-small cell lung cancer (NSCLC) are relatively insensitive and unsatisfactory. Para-toluenesulfonamide (PTS), a unique antitumor drug for local intratumoral injection, shows an efficacy of severely suppressing solid tumor growth with mild side effects in clinical trials. The aim of this study was to investigate the effect of PTS on lung cancer H460 cells in vivo in nude mice and its underlying mechanisms in vitro. METHODS: A lung cancer model for in vivo experiment was established in BALB/c nude mice using H460 cells to examine the effect of local injection of PTS on tumor suppression. We also assessed the injury to the normal tissue by subcutaneous injection of PTS. In vitro, PTS was diluted into different doses for study on its antitumor mechanisms. We evaluated the necrotic effect of PTS on H460 cells by PI and Hoechst 33342 staining. Cell viability and membrane permeability were also determined by using CCK-8 and LDH assays respectively. All these tests were conducted in comparison with traditional local injection of anhydrous ethanol. RESULTS: PTS was shown to significantly inhibit the growth of H460 tumor xenografts in nude mice by inducing necrosis of the tumor histologically. Its effect on tumor growth was significantly stronger than that of anhydrous ethanol. By contrast, the injured normal tissue by PTS injection was less than that by ethanol. In vitro, PTS still demonstrated excellent necrotizing effect on H460 cells when diluted to a lower concentration. Detailed analysis of PTS on H460 cells indicated that PTS had a better effect on attenuating the cell viability and increasing the cell membrane permeability than ethanol at the same level. CONCLUSIONS: PTS exhibits excellent inhibition effect on the growth of lung cancer by necrotizing tumor in vivo and in vitro, reducing tumor cell viability and augmenting the membrane permeability in vitro, with only mild injury to normal tissue. The antitumor effect of PTS on lung cancer in vivo and in vitro is stronger than that of ethanol.