Cardiac-specific deletion of BRG1 ameliorates ventricular arrhythmia in mice with myocardial infarction.

Malignant ventricular arrhythmia (VA) after myocardial infarction (MI) is mainly caused by myocardial electrophysiological remodeling. Brahma-related gene 1 (BRG1) is an ATPase catalytic subunit that belongs to a family of chromatin remodeling complexes called Switch/Sucrose Non-Fermentable Chromatin (SWI/SNF). BRG1 has been reported as a molecular chaperone, interacting with various transcription factors or proteins to regulate transcription in cardiac diseases. In this study, we investigated the potential role of BRG1 in ion channel remodeling and VA after ischemic infarction. Myocardial infarction (MI) mice were established by ligating the left anterior descending (LAD) coronary artery, and electrocardiogram (ECG) was monitored. Epicardial conduction of MI mouse heart was characterized in Langendorff-perfused hearts using epicardial optical voltage mapping. Patch-clamping analysis was conducted in single ventricular cardiomyocytes isolated from the mice. We showed that BRG1 expression in the border zone was progressively increased in the first week following MI. Cardiac-specific deletion of BRG1 by tail vein injection of AAV9-BRG1-shRNA significantly ameliorated susceptibility to electrical-induced VA and shortened QTc intervals in MI mice. BRG1 knockdown significantly enhanced conduction velocity (CV) and reversed the prolonged action potential duration in MI mouse heart. Moreover, BRG1 knockdown improved the decreased densities of Na+ current (INa) and transient outward potassium current (Ito), as well as the expression of Nav1.5 and Kv4.3 in the border zone of MI mouse hearts and in hypoxia-treated neonatal mouse ventricular cardiomyocytes. We revealed that MI increased the binding among BRG1, T-cell factor 4 (TCF4) and ß-catenin, forming a transcription complex, which suppressed the transcription activity of SCN5A and KCND3, thereby influencing the incidence of VA post-MI.

Effect of alfalfa supplementary change dietary non-fibrous carbohydrate (NFC) to neutral detergent fiber (NDF) ratio on rumen fermentation and microbial function in Gansu alpine fine wool sheep (Ovis aries).

Bodyweight loss and rumen microbial dysfunction of grazing sheep was a challenge for the sheep production industry during cold season, which were considered to correlated with under-roughage-feeding. Alfalfa is a good roughage supplementary for ruminants, which can improve grazing sheep bodyweight-loss and rumen microbial dysfunction during grass-withering period. This study evaluated the effects of alfalfa hay supplementary change dietary non-fibrous carbohydrate/neutral detergent fiber (NFC/NDF) ratios on rumen fermentation and microbial function of Gansu alpine fine wool sheep during extreme cold season. 120 ewes (3-4 yrs) with an average body weight of 28.71 ± 1.22 kg were allocated randomly into three treatments, and fed NFC/NDF of 1.92 (H group), 1.11 (M group), and 0.68 (L group), respectively. This study was conducted for 107 d, including 7 d of adaption to the diets. The rumen fermentation parameters and microbial characteristics were measured after the end of feeding trials. The results showed that the concentrations of sheep body weight, nitrogen components (Total-N, Soluble protein-N and Ammonia-N), blood biochemical indices (LDH, BUN and CHO) and ruminal volatile fatty acids (TVFA and propionate) significantly increased with an increase in the proportion of NFC/NDF ratios (p < .05), and the acetate and acetate/propionat ratio presented a contrary decreasing trend (p < .05). A total of 1018 OTUs were obtained with 97% consistency. Ruminococcus, Ruminococcaceae and Prevotella were observed as the predominant phyla in ruminal fluid microbiota. Higher NFC/NDF ratios with Alfalfa supplementary increased the richness and diversity of ruminal fluid microbiota, and decreased ruminal fluid microbiota beta-diversity. Using clusters of orthologous groups (COG), the ruminal fluid microbiota of alfalfa supplementary feeding showed low immune pathway and high carbohydrate metabolism pathway. In summary, the study suggested that there was an increasing tendency in dietary NFC/NDF ratio of 1.92 in body weight, ruminal fermentation, microbial community composition and fermentation characteristics through developing alfalfa supplementary system.

The role of BRG1 in epigenetic regulation of cardiovascular diseases.

Cardiovascular diseases have been closely linked to abnormal epigenetic regulation. In the context of epigenetic regulation, BRG1, a pivotal SWI/SNF chromatin remodeling enzyme, emerges as a key epigenetic regulator with significant impact on the development and progression of cardiovascular disorders. From the perspective of epigenetic regulation of cardiovascular diseases, BRG1 emerges as a pivotal SWI/SNF chromatin remodeling enzyme, functioning as a key epigenetic regulator. It exerts substantial influence on the development and progression of cardiovascular disorders by exerting precise control over gene expression and protein levels. Therefore, a comprehensive understanding of BRG1's epigenetic regulatory role in cardiovascular disease is essential for unraveling its underlying pathophysiological mechanisms. This paper summarizes and discusses the function of BRG1 in the epigenetic regulation of cardiovascular diseases.

Corrigendum: Non-alcoholic fatty liver disease is associated with aortic calcification: a cohort study with propensity score matching.

[This corrects the article DOI: 10.3389/fendo.2022.880683.].

PFI-3 induces vasorelaxation with potency to reduce extracellular calcium influx in rat mesenteric artery.

Background: PFI-3 is a small-molecule inhibitor that targets the bromodomains (BRDs) of Brahma-related gene 1 (BRG1). This monomeric compound, which has high selectivity and potent cellular effects, has recently been developed. Although PFI-3 has been reported as a potential therapeutic agent targeting thrombomodulin, its role in the regulation of vascular function remains unknown. Therefore, we aimed to investigate the impact of PFI-3 on arterial vessel tone. Methods: A microvascular tension measurement device (DMT) was utilized to identify alterations in vascular tension within the mesenteric artery. To detect variations in cytosolic [Ca2+]i, a Fluo-3/AM fluorescent probe and fluorescence microscope were employed. Additionally, whole-cell patch clamp techniques were utilized to evaluate the activity of L-type voltage-dependent calcium channels (VDCCs) in cultured arterial smooth muscle cells (A10 cells). Results: PFI-3 exerted a dose-dependent relaxation effect on rat mesenteric arteries with both intact and denuded endothelium after phenylephrine (PE)- and high-K+-induced constriction. PFI-3-induced vasorelaxation was not affected by the presence of L-NAME/ODQ or K+ channel blockers (Gli/TEA). PFI-3 abolished Ca2+-induced contraction on endothelium-denuded mesenteric arteries preincubated by PE in Ca2+-free solution. Incubation with TG had no impact on PFI-3-induced vasorelaxation pre-contracted by PE. PFI-3 reduced Ca2+-induced contraction on endothelium-denuded mesenteric arteries pre-incubated by KCl (60 mM) in Ca2+-free solution. PFI-3 declined extracellular calcium influx in A10 cells detected by Fluo-3/AM fluorescent probe and fluorescence microscope. Furthermore, we observed that PFI-3 decreased the current densities of L-type VDCC by whole-cell patch clamp techniques. Conclusions: PFI-3 blunted PE and high K+-induced vasoconstriction independent of endothelium on rat mesenteric artery. The vasodilatory effect of PFI-3 may be attributed to its inhibition of VDCCs and receptor-operated calcium channels (ROCCs) on vascular smooth muscle cells (VSMCs).

Translation and validation of the Chinese version of the orthorexia nervosa assessment questionnaires among college students.

PURPOSE: The main objective of the study was to translate, validate, and compare the Chinese ORTO scales (ORTO-15 and ORTO-R). The secondary objective was to assess factors that may be related with risk of orthorexia nervosa (ON). METHODS: Two cross-sectional surveys were conducted on March-to-June 2021 for ORTO-15 and April 2022 for ORTO-R. ORTO questionnaires were translated into Chinese using the forward-backward-forward method. Exploratory factor analysis (EFA), discriminant validity and confirmatory factor analysis (CFA) were used to examine the construct validity of the questionnaires. The internal consistency was assessed using the Cronbach alpha coefficient and the test-retest reliability. Multivariate linear regression analysis was used to explore potential factors related with ON scores. RESULTS: Totally, 1289 and 1084 eligible participants were included for assessment of ORTO-15 and ORTO-R, with the mean age of 20.9 ± 2.0 years and 21.0 ± 2.3 years. The internal consistency of Chinese ORTO-15 scale and ORTO-R scale were both satisfactory (α = 0.79, ICC = 0.79; α = 0.77, ICC = 0.82). However, all ORTO-15 models showed a poor fit using CFA whereas the ORTO-R was characterized by acceptable goodness-of-fit. Multivariate linear regression indicated that physical activities and mental disorders were positively associated with ON risk assessed by both ORTO-R and ORTO-15. CONCLUSION: The Chinese ORTO-R scale was a more reliable tool to screen for ON tendencies than the Chinese version of ORTO-15. Mental disorders and physical activities might be associated with the increased ON risk. LEVEL OF EVIDENCE: Level V (descriptive cross-sectional study).

Global, Regional, and National Burden of Cancer in Children Younger Than 5 Years, 1990-2019: Analysis of the Global Burden of Disease Study 2019.

Objectives: To quantify the burden and variation trends of cancers in children under 5 years at the global, regional, and national levels from 1990 to 2019. Methods: Epidemiological data for children under 5 years who were diagnosed with any one childhood cancer were obtained from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) from 1990 to 2019. The outcomes were the absolute numbers and rates of incidence, prevalence, mortality, and disability-adjusted life-years (DALYs) for different types of cancer. Results: In 2019, 8,774,979.1 incident cases (95% uncertainty interval [UI]: 6,243,599.2 to11,737,568.5) and 8,956,583.8 (6,446,323.9 to 12,364,520.8) prevalent cases of cancer in children under 5 years were identified worldwide; these cancers resulted in 44,451.6 (36,198.7 to 53,905.9) deaths and 3,918,014.8 (3,196,454.9 to 4,751,304.2) DALYs. From 1990 to 2019, although the numbers of incident and prevalent cases only decreased by -4.6% (-7.0 to -2.2) and -8.3% (-12.6 to -3.4), respectively, the numbers of deaths and DALYs clearly declined by -47.8% (-60.7 to -26.4) and -47.7% (-60.7 to -26.2), respectively. In 2019, the middle sociodemographic index (SDI) regions had the highest incidence and prevalence, whereas the low SDI regions had the most mortality and DALYs. Although all of the SDI regions displayed a steady drop in deaths and DALYs between 1990 and 2019, the low-middle and low SDI regions showed increasing trends of incidence and prevalence. Leukemia remained the most common cancer globally in 2019. From 1990 to 2019, the burdens of leukemia, liver cancer, and Hodgkin's lymphoma declined, whereas the incidence and prevalence of other cancers grew, particularly testicular cancer. Conclusions: The global childhood cancer burden in young children has been steadily decreasing over the past three decades. However, the burdens and other characteristics have varied across different regions and types of cancers. This highlights the need to reorient current treatment strategies and establish effective prevention methods to reduce the global burden of childhood cancer.

Non-alcoholic Fatty Liver Disease Is Associated With Aortic Calcification: A Cohort Study With Propensity Score Matching.

Objectives: Non-alcoholic fatty liver disease (NAFLD) greatly affects cardiovascular disease, but evidence on the associations between NAFLD and markers of aortic calcification is limited. We aim to evaluate the association between NAFLD and aortic calcification in a cohort of Chinese adults using propensity score-matching (PSM) analysis. Methods: This prospective cohort study involved adults who underwent health-screening examinations from 2009 to 2016. NAFLD was diagnosed by abdominal ultrasonography at baseline, and aortic calcification was identified using a VCT LightSpeed 64 scanner. Analyses included Cox proportional-hazards regression analysis and PSM with predefined covariates (age, gender, marital and smoking status, and use of lipid-lowering drugs) to achieve a 1:1 balanced cohort. Results: Of the 6,047 eligible participants, 2,729 (45.13%) were diagnosed with NAFLD at baseline, with a median age of 49.0 years [interquartile range, 44.0-55.0]. We selected 2,339 pairs of participants with and without NAFLD at baseline for the PSM subpopulation. Compared with those without NAFLD, patients with NAFLD were at a higher risk of developing aortic calcification during follow-up; significant results were observed before and after matching, with the full-adjusted hazard ratios and corresponding 95% confidence intervals being 1.19 (1.02-1.38) and 1.18 (1.01-1.38), respectively (both p < 0.05). In subgroup analyses, no interaction was detected according to age, gender, smoking status, body mass index, total cholesterol, low-density lipoprotein cholesterol, use of lipid-lowering drugs, hypertension, or type 2 diabetes. Conclusions: NAFLD may be independently associated with aortic calcification. Further studies are warranted to elucidate the possible underlying mechanisms.

MiR-325-3p Alleviates Acute Pancreatitis via Targeting RIPK3.

BACKGROUND AND AIMS: Acute pancreatitis (AP) is an acute inflammatory disease that can lead to death. Mir-325-3p is strongly and abnormally expressed in many diseases, necessitating exploration of its function and mechanism in AP. METHODS: Blood samples from AP patients and mice were analyzed. The expression levels of miR-325-3p in AP patients and mouse were detected. Whether miR-325-3p targets RIPK3 gene was predicted by TargetScan online database and dual luciferase reporter assay. In vitro experiments verified the effect of miR-325-3p overexpression on caerulein-induced MPC83 pancreatic acinar cancer cell line. In vivo experiments verified the effect of overexpression of miR-325-3p on the disease degree of pancreatic tissues in AP mice. RESULTS: Analysis of blood samples from AP patients and experiments in mice demonstrated that expression of miR-325-3p was significantly reduced during the process of AP in humans and mice. Predicted using the TargetScan online database and through dual luciferase reporter assay detection, miR-325-3p directly targets the RIPK3 gene. In vitro experiments revealed that overexpression of miR-325-3p reversed caerulein-induced apoptosis and necroptosis in MPC83 pancreatic acinar cancer cell line. We used Z-VAD-FMK to assess necroptosis and demonstrated that miR-325-3p targets necroptosis to reduce cell damage. In subsequent experiments in mice, we verified that overexpression of miR-325-3p reduces inflammation, edema, hemorrhage, and necrosis in acute pancreatitis. Characteristic western blot, immunohistochemistry, and transmission electron microscopy results revealed that overexpression of miR-325-3p reduces the severity of acute pancreatitis by inhibiting pancreatic necroptosis in AP mice. CONCLUSIONS: The current research results indicate that miR-325-3p directly targets RIPK3 and exerts a protective role in mouse AP. Necroptosis is still the primary mechanism of RIPK3 regulation. MiR-325-3p inhibits acute pancreatitis by targeting RIPK3-dependent necroptosis, which may represent a novel treatment method for acute pancreatitis.

Physical activity, screen exposure and sleep among students during the pandemic of COVID-19.

This study aimed to determine the levels of health-related behaviours (physical activity, screen exposure and sleep status) among Chinese students from primary, secondary and high schools during the pandemic of COVID-19, as well as their changes compared with their status before the pandemic. A cross-sectional online survey of 10,933 students was conducted among 10 schools in Guangzhou, China, between 8th and 15th March, 2020. After getting the informed consent from student's caregivers, an online questionnaire was designed and used to obtain time spending on health-related behaviours during the pandemic of COVID-19, as well as the changes compared with 3 months before the pandemic, which was completed by students themselves or their caregivers. Students were stratified by regions (urban, suburban, exurban), gender (boys and girls), and grades (lower grades of primary school, higher grades of primary schools, secondary schools and high schools). Data were expressed as number and percentages and Chi-square test was used to analyse difference between groups. Overall, the response rate of questionnaire was 95.3% (10,416/10,933). The median age of included students was 13.0 (10.0, 16.0) years and 50.1% (n = 5,219) were boys. 41.4%, 53.6% and 53.7% of total students reported less than 15 min per day in light, moderate and vigorous activities and 58.7% (n = 6,113) reported decreased participation in physical activity compared with the time before pandemic. Over 5 h of screen time spending on online study was reported by 44.6% (n = 4,649) of respondents, particular among high school students (81.0%). 76.9% of students reported increased screen time compared with the time before pandemic. Inadequate sleep was identified among 38.5% of students and the proportion was highest in high school students (56.9%). Our study indicated that, during the COVID-19 pandemic, the school closure exerted tremendous negative effects on school-aged children's health habits, including less physical activity, longer screen exposure and irregular sleeping pattern.

Association between blood urea nitrogen and incidence of type 2 diabetes mellitus in a Chinese population: a cohort study.

To examine the association between blood urea nitrogen (BUN) and risk of type 2 diabetes (T2DM) among Chinese adults, we performed an ongoing cohort study of 38578 Chinese adults (56.3% males; average age, 41.6 y) who underwent repeated health check-up examinations between 2009 and 2016 and without T2DM at baseline. During follow-up, incident T2DM cases were identified based on self-report, medication use, measurements of fasting plasma glucose, 2 h post oral glucose, or haemoglobinA1c. 2009 (5.2%) cases confirmed with incident T2DM were identified during median follow-up of 3.1 years. With increasing quartiles of BUN levels, the incidences of T2DM gradually increased with 0.69%, 1.11%, 1.53%, and 1.87% for quartile 1 to quartile 4 (p trend <0.001). Compared with quartile 1, the multivariate-adjusted hazard ratios (HRs) and its 95% confidence intervals (95% CIs) for T2DM risk were 1.16 (0.97-1.38) for quartile 2, 1.28 (1.07-1.51) for quartile 3, and 1.28 (1.08-1.52) for quartile 4 (p trend = 0.005). HR for per each standard deviation increase in BUN level was 1.10 (1.04-1.16) (p trend <0.001). This association tended to be more pronounced in those with a lower body mass index at baseline (p-interaction <0.001). Our results suggested that BUN levels were positively associated with incident T2DM risk among Chinese adults. Future prospective investigations in other populations are necessary to confirm our findings.

The association between dietary fatty acid intake and the risk of developing preeclampsia: a matched case-control study.

The association between dietary fat intake during pregnancy and the risk of developing preeclampsia has been examined in many epidemiological studies, but the results remain inconsistent. The aim of this study was to clarify this association in pregnant Chinese women. After conducting 1:1 matching, 440 pairs consisting of pregnant women with preeclampsia and hospital-based, healthy pregnant women matched by gestational week (± 1 week) and age (± 3 years) were recruited. A 79-item semi-quantitative food frequency questionnaire administered during face-to-face interviews was used to estimate the participants' dietary intake of fatty acids. We found that the intakes of arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) were inversely associated with the risk of developing preeclampsia. Compared with the lowest quartile intake, the multivariate-adjusted odds ratios (95% confidence interval) of the highest quartile intake were 0.42 (0.26-0.68, p-trend < 0.001) for EPA, 0.52 (0.3-0.83, p-trend = 0.005) for DHA, and 0.41 (0.19-0.88, p-trend = 0.007) for AA. However, we did not observe any significant associations between the intake of total fatty acids, saturated fatty acids, and mono-unsaturated fatty acids and the risk of developing preeclampsia. Our results showed that the dietary intake of long-chain polyunsaturated fatty acids (i.e., EPA, DHA, and AA) may protect pregnant Chinese women against the development of preeclampsia.

Association between serum prostate-specific antigen concentrations and the risk of developing type 2 diabetes mellitus in Chinese men: A cohort study.

AIMS/INTRODUCTION: The current literature suggests that men with diabetes have a lower prostate-specific antigen concentration than men without diabetes, but the causal association remains unclear. We aimed to investigate the association between serum prostate-specific antigen concentrations and the risk of type 2 diabetes mellitus in a cohort study of a Chinese population. MATERIALS AND METHODS: We designed a cohort study that comprised 16,811 initially non-diabetic Chinese men who received annual health checkups between 2009 and 2016. The outcome of this study was type 2 diabetes mellitus, identified by medical diagnosis, self-reportage, medication use, fasting glucose, 2-h post oral glucose or glycated hemoglobin measurements. Cox proportional hazards models were carried out to evaluate the association. RESULTS: During a median follow-up period of 3.8 years (interquartile range 1.91-5.73 years), 1,260 participants developed incident type 2 diabetes mellitus. The multivariable model, adjusted for various potential confounders, showed that serum prostate-specific antigen concentrations were inversely related to type 2 diabetes mellitus risk (P for trend = 0.014). Compared with the lowest quartile of serum prostate-specific antigen, the hazard ratio and 95% confidence intervals of type 2 diabetes mellitus risk for quartile 2-4 were 0.84 (0.66-1.07), 0.75 (0.59-0.94) and 0.77 (0.62-0.96), respectively. Subgroup analyses suggested the inverse relationship was more prominent in overweight or obese participants (P for interaction = 0.013). CONCLUSIONS: High serum prostate-specific antigen concentration was associated with a low risk of type 2 diabetes mellitus in Chinese men. Future studies are required to confirm these findings and investigate underlying mechanisms.

lncRNA Signature for Predicting Cerebral Vasospasm in Patients with SAH: Implications for Precision Neurosurgery.

Subarachnoid hemorrhage (SAH) patients' surgery is performed to prevent extravasation of blood into the subarachnoid space. Cerebral vasospasm (CVS; narrowing of cerebral arteries) occurs following SAH and represents a major cause of associated mortality and morbidity. To improve postsurgery care of SAH patients and their prognosis, the ability to predict CVS onset is critical. We report a long noncoding RNA (lncRNA) signature to distinguish SAH patients with CVS from SAH patients without CVS. Cerebrospinal fluid (CSF) was obtained from SAH patients without CVS (n = 10) and SAH patients with CVS (n = 10). lncRNAs ZFAS1 and MALAT1 were significantly upregulated (p < 0.05), whereas lncRNAs LINC00261 and LINC01619 were significantly downregulated in SAH patients with CVS (p < 0.05) compared to SAH patients without CVS. We applied this lncRNA signature to retrospectively predict CVS in SAH patients (n = 38 for SAH patients without CVS, and n = 27 for SAH patients with CVS). The 4-lncRNA signature was found to be predictive in >40% of samples and the 2-lncRNA comprising MALAT1 and LINC01619 accurately predicted CVS in ∼90% cases. These results are initial steps toward personalized management of SAH patients in clinics and provide novel CSF biomarkers that can substantially improve the clinical management of SAH patients.

The impacts of infectious complications on outcomes in acute pancreatitis: a retrospective study.

BACKGROUND: The occurrence of infectious complications characterizes the more severe forms of acute pancreatitis (AP) and is associated with high mortality. We investigated the effects of infection at different sites in patients with AP, including those with necrotizing pancreatitis (NP). METHODS: We conducted a retrospective analysis of 285 patients who met the inclusion criteria for AP and were admitted to Tianjin Nankai Hospital between January 2016 and September 2019. According to the source of the culture positivity during hospitalization, patients were divided into four groups: sterile group(n = 148), pancreatic infection group(n = 65), extrapancreatic infection group(n = 22) and combined infection group(n = 50). The source of infection, microbiology, biochemical parameters and prognostic indicators were analyzed. RESULTS: In terms of baseline characteristics, the four groups were similar in age, sex, aetiology, previous pancreatitis and diabetes. Compared with the severity of the disease in the other groups, the APACHE II scores(9.91 ± 4.65, 9.46 ± 5.05, respectively) and organ failure rate (40.9 and 50%, respectively)were higher in the extrapancreatic infection group and the combined infection group (P < 0.05). The frequency of surgical intervention and hospitalization time in patients with NP complicated with extrapancreatic infection was greatly increased (P < 0.05). Regarding the primary outcome, patients in the combined infection group had longer hospital stays (68.28 ± 51.80 vs 55.58 ± 36.24, P < 0.05) and higher mortality (24.0% vs 9.2%, P < 0.05) than patients in the pancreatic infection group. In addition, patients in the extrapancreatic infection group also showed high intensive care utilization (59.1%) and mortality rates (18.2%). Among the 137 AP patients with infection complications, 89 patients exhibited multidrug-resistant (MDR) microorganisms, and the mortality rate of patients with MDR bacterial infection was higher than that of patients with non-MDR bacterial infection (24.7% vs 3.6%, P = 0.001). CONCLUSION: Clinicians should be aware that extrapancreatic infection (EPI) significantly aggravates the main outcome in pancreatic infection patients. Infection with MDR bacteria is also associated with AP mortality.

Anesthetic propofol epigenetically regulates breast cancer trastuzumab resistance through IL-6/miR-149-5p axis.

Propofol, a common intravenous anesthetic, has been found to exert anti-cancer effects with inhibition of cancer cell proliferation, migration and invasion. We tested its possible action against HER2-overexpressing breast cancer cells that developed resistance against trastuzumab. Cell viability assay, ELISA for cytokines, mammosphere formation, quantitative RT-PCR for EMT/IL-6-targeting miRNAs and the in vivo experimental pulmonary metastasis model were performed to understand the epigenetic action of propofol. Propofol sensitized HER2 overexpressing cells to trastuzumab but such action was even more pronounced in resistant cells. Increased cytokines IL-6 as well as IL-8 were released by resistant cells, along with increased mammospheres and induction of EMT, all of which was inhibited by propofol. IL-6 targeting tumor suppressor miR-149-5p was found to be the novel miRNA that was up-regulated by propofol, resulting in the observed effects on cell viability, IL-6 production, mammospheres generation as well as EMT induction. Further, antagonizing miR-149-5p attenuated the propofol effects confirming the epigenetic activity of propofol through miR-149-5p regulation. Finally, in vivo validation in an experimental metastasis model conformed an inhibitory action of propofol against experimental lung metastasis and the essential mechanistic role of miR-149-5p/IL-6 loop. These results present a novel role of general anesthetic propofol against resistant breast cancer cells and the underlying epigenetic regulation of a tumor suppressor miRNA.

Ketamine a dissociative anesthetic: Neurobiology and biomolecular exploration in depression.

Ketamine is gaining ground as a potential treating depression because it has a distinct mode of action than typical drugs that influence monoamine neurotransmitters including noradrenaline, dopamine, or serotonin. Ketamine is thought to act by blocking N-methyl-d-aspartate (NMDA) receptors in the brain, which interact with the amino acid neurotransmitter glutamate. The resultant chemical changes in the brain caused by ketamine are not yet fully understood but could involve ketamine-induced gene expression and signaling cascades that act long after the drug has been eliminated from the body. Despite these remarkable effects, the widespread use of ketamine is limited by potential side effects including the emergence reactions (hallucinations, dreams, and out-of-body experiences) by recreational users, who need further study before long-term use of ketamine can be approved for depression. Thus, studies are necessary to further elucidate mechanistic actions of ketamine at cellular and network levels. Thus, we are exploring the involvement of molecular targets for the treatment and psychomimetic phenomena of the ketamine.

Overactivation of the sodium-calcium exchanger and transient receptor potential in anesthesia-induced malignant hyperthermia.

Malignant hyperthermia is a pharmacogenetic disorder, which is an uncommon but frequently fatal intricacy of inhalation anesthesia in man. It causes a quick rise in body temperature to highly irreversible levels, which causes death in around three of four cases. The trigger anesthetics cause an anomalous, continued ascent in myoplasmic calcium levels. Possible mechanisms by which continuous release of sodium, calcium from skeletal muscle plasma membrane and sarcoplasmic reticulum stores respectively can produce the profound hyperthermia are discussed.

Overexpression of sterol carrier protein-2 mRNA in patients with cholesterol gallstones.

BACKGROUND: Hypersecretion of biliary cholesterol is believed to be one of the important causes of lithogenic bile. Sterol carrier protein-2(SCP2) participates in cholesterol trafficking and metabolism and may play a key role in cholesterol gallstone formation. This study was undertaken to investigate the expression of liver SCP2 mRNA in patients with cholesterol gallstone and those patients with non-cholesterol gallstone. METHODS: The expression of liver SCP2mRNA was studied in 36 patients with cholesterol gallstone and 30 patients with non-cholesterol gallstone by reverse transcription-polymerase chain reaction (RT-PCR). RESULT: The expression of SCP2 mRNA was increased more significantly in patients with cholesterol gallstone than in patients with non-cholesterol gallstone. CONCLUSION: The SCP2 gene was overexpressed in patients with cholesterol gallstone, indicating that SCP2 may be one of the important causes of cholesterol gallstone.