bluuebunny/crossref_metadata_2025_split huggingface dataset:
Heat shock protein 72 inhibits vascular calcification through a PPAR‐dependent pathway
Authors: Soong Ya‐Hue , Xu Jen , Zhuang Jun‐Cheng , Kong Tianqing , Lu Tzongshi 
Published: June 2021

Cardiovascular disease (CVD) is the leading cause of mortality globally and caused approximately 600,000 people decease annually in the United States. Vascular calcification (VC) is a significant contributor to CVD mortality in patients with Chronic Kidney Disease and Coronary Heart Disease. We recently reported that heat shock protein 72 (HSP72) can be induced in human arteries and prevent VC. However, the molecular mechanisms of HSP72 involved in VC have yet to be elucidated.Our results show that inducible HSP72 is significantly expressed following heat shock treatment and abolished by HSP72 siRNA, as well as HSP72 mediated anti‐calcification in HA‐SMCs. We next show that HSP72 gene is significant down regulated at HA‐SMCs and human arteries. In addition, we found that the peroxisome proliferator‐activated receptors γ (PPARγ) inhibitors (CCL4 (chemokine (C‐C motif) ligand 4) and FABP4 (fatty acid binding protein‐4)) and transcription factor AP‐1 (activator protein‐1) that involved in atherosclerosis, cellular transformation and cell death were up‐regulated in calcified human arteries. And. Our data shows that HSP72 formed a protein‐protein complex with PPARγ by co‐immunoprecipitation. Lastly, induction of HSP72 restored expression of the HSP72‐PPARγ complex and inhibited up‐regulation of FABP4, AP‐1 with reduction in calcification in our in vitro calcification model. These vasculo‐protective effects were abolished by HSP72 siRNA.In conclusion, HSP72 is a powerful inhibitor of VC and exerts its vasculo‐protective effects by functioning as a molecular chaperon through PPARγ dependent pathway.
Calcineurin Alpha Inhibition Induces Nox2 Up‐regulation via NFκB
Authors: Williams Clintoria , Hoover Robert , Gooch Jennifer 
Published: June 2021

Although essential for preventing transplant rejection, prolonged calcineurin inhibitor (CNI) use induces nephrotoxicity. We showed that mice lacking the alpha catalytic isoform of calcineurin (CnAα) have a phenotype that mirrors CNI nephrotoxicity. Other studies implicate NADPH oxidase‐2 (Nox2) in the pathogenesis. This study seeks to determine if CnAα and Nox2 function in a common pathway. To determine the mechanism of CNI inhibition‐mediated increases in renal Nox2, WT mice were treated with cyclosporine A (CsA) for 6 weeks. In addition, Nox2 expression and activity were examined in CnAα‐/‐ and CnAβ‐/‐ mice and renal fibroblasts. In kidneys, co‐IP reveals that CsA treatment reduces CnAα association with its binding partner, calmodulin. Consistent with previous data, CnAβ and calmodulin association is not observed. Additionally, reduced CnAα activation is accompanied by increased Nox2 expression and ROS levels, as assessed by Western blot and Amplex Red. Consistently, renal Nox2 expression and ROS levels are increased in CnAα‐/‐ mice but not CnAβ‐/‐. Surprisingly, NFAT transcriptional activity is unchanged in CnAα‐/‐ mice compared to WT and CnAβ‐/‐, as assessed by luciferase activity. However, increased NFκB phosphorylation is observed. In CnAα‐/‐ cells, NFκB inhibition with CAPE attenuates enhanced Nox2 expression and ROS levels. In conclusion, these data indicate that CsA‐induced CnAα inhibition and subsequent NFκB activation stimulates Nox2 up‐regulation. Therapeutic approaches using CNI that do not target CnAα could ameliorate oxidative damage associated with CNI nephrotoxicity.NIH‐T32 (CRW), NIH‐R01 (RSH), VA‐MERIT (JLG)
Changes in Arterial Stiffness and Blood Pressure during Various Vascular Reactivity Tests
Authors: Lim Jisok , Pearman Miriam , alkatan Mohammed , Machin Daniel , Park Wonil , Tanaka Hirofumi 
Published: June 2021

Increased arterial stiffness is an independent marker of cardiovascular risk. However, some investigators have questioned the utility of arterial stiffness above and beyond the traditional blood pressure (BP) measurement as the change in arterial stiffness is often accompanied by corresponding changes in BP. Although the associations between chronic levels of arterial stiffness and BP have been fairly well studied, it is unclear if and how much arterial stiffness is influenced by acute BP changes.PURPOSETo determine the magnitude of BP‐dependence of arterial stiffness during acute BP perturbations.METHODSThirty apparently healthy subjects (46±4 years; 17 males) were studied. BP perturbations, including head‐up tilt, head‐down tilt, mental stress, isometric handgrip exercise, and cold pressor test were used to encompass blood pressure changes induced by physical, mental, and/or physiological stimuli. Arterial stiffness was measured with carotid‐femoral pulse wave velocity (PWV).RESULTSPWV was significantly associated with mean BP at rest (r=0.42). Mean BP was significantly changed during each perturbation, and changes ranged from △5±4 to △22±4 mmHg. Changes in mean BP and PWV were significantly correlated during mental stress (r=0.44), handgrip exercise (r=0.55), and cold pressor test (r=0.39). Significant associations were not found during head‐up tilt and head‐down tilt. CONCLUSIONThis study demonstrates that changes in arterial stiffness, as assessed by PWV, are significantly associated with acute BP changes during some BP perturbations but BP‐dependence of arterial stiffness is not observed in all perturbations.Supported by Fukuda Denshi.
Hepatocellular Carcinoma Specific Transcriptional Interference of c‐Myc promoter by alpha‐fetoprotein and Sendai Virosome Based dsRNA System
Authors: Zakaria Mohammad Khalid , Khan Imran , Mani Prashant , Chattopadhyay Parthaprasad , Sarkar Debi P. , Sinha Subrata 
Published: June 2021

Objectivec‐Myc is one of the central players of oncogenesis in hepatocellular carcinoma (HCC) and is also required in normal development. Majority of the c‐Myc transcripts are transcribed by its P2 promoter and an upstream ME1a1 site is required in its transcriptional activation. dsRNA also recruits epigenetic silencing complexes inducing long term/heritable transcriptional repression. We devised a novel HCC targeting system and studied its mechanism.MethodsFirstly, the alpha‐fetoprotein (AFP) promoter/enhancer system was used to express shRNA against ME1a1 site. Secondly, we transformed Sendai virus into fusion (F) virosomes for packaging and delivery of AFP promoter/enhancer driven shRNA constructs into liver cells.ResultsFollowing F‐virosomal delivery, shRNA induced heterochromatization (H3K9Me2 and H3K27Me3) and CpG 8,9,10 methylation at the target locus. Following c‐Myc suppression, HCC cells showed decreased cell survival and increased apoptosis. Also, c‐Myc suppressed HCC cells were sensitized to sub lethal doses of 5‐Fluorouracil (5‐FU) and Cisplatin.ConclusionThis system can specifically and prominently repress c‐Myc in HCC cells and could also be used to introduce genes specifically in embryonic liver.Grant Funding Source: Department of Biotechnology, Govt. of India
Reduced Transcobalamin I Gene Expression Following Roux‐en‐Y Gastric Bypass Surgery Can Contribute to B12 Deficiency
Authors: Sala Priscila , Machado Natasha , Belarmino Giliane , Ishida Robson , Guarda Ismael , Giannella‐Neto Daniel , Santo Marco Aurelio , Moura Eduardo , Sakai Paulo , Silva Ismael , Ye Jianping , Heymsfield Steven , Waitzberg Dan 
Published: June 2021

The objective of this study was to examine potential mechanisms leading to the often‐observed Vitamin B12 deficiency following Roux‐en‐Y gastric bypass (RYGB). Vitamin B12 absorption begins with release from food in the upper GI tract followed by transcobalamin I binding; duodenal enzyme degradation of transcobalamin I is then followed by intrinsic factor (IF) capture; IF is next degraded within the ileal enterocyte, releasing B12 that then enters the plasma. Although IF levels are reduced with RYGB due to removal of the gastric fundus, other causes of modified B12 transport may be involved. To examine these other potential mechanisms we used balloon endoscopy to acquire GI tissue at multiple sites in 20 obese women with adult‐onset diabetes before (age, 46.5±6.6 yrs; BMI, 45.7±4.1 kg/m2) RYGB and at the identical India‐Ink marked sites three months following surgery (BMI, 37.7±3.4 kg/m2). Microarray analysis was performed on all samples using a Human GeneChip 1.0 ST array (Affymetrix, Inc., Santa Clara, CA). There was significantly reduced gene expression (2.335‐fold, p<0.05) of TCN1 in the remnant stomach following surgery (TCN1 translates transcobalamin I). These findings suggest that B12 deficiency following RYGB may be caused by a reduction in transcobalamin I in addition to the anatomical absence of IF.FAPESP 2011/09612‐3, BEPE 2014/07742‐5.
Doxycycline Prevents Right Ventricular Dysfunction Induced by Pulmonary Embolism
Authors: Neves Evandro , Kline Jeffrey 
Published: June 2021

Pulmonary embolism (PE) is commonly associated to right ventricular (RV) dysfunction, which predict poor outcome. Doxycycline pretreatment has been associated to beneficial effects after PE. However, no previous study has evaluated doxycycline posttreatment.Male Sprague‐Dawley rats (300‐350g) were anaesthetized with ketamine and xylazine. On day 1, the PE group received 85 µm polystyrene microspheres (221.000/100 g body wt, jugular vein) suspended in 0.01% Tween 20 and the Sham group received Tween only. Treatment animals received doxycycline (Doxy, 30mg/kg by gavage) and Controls received volume‐matched saline for 5 days after PE induction. Hearts were then extirpated from anesthetized animals on day 5 and perfused via the aorta using Langendorff technique with Krebs‐Henseleit buffer. We explored the Frank‐Starling relationship of RV contractile function (RV developed pressure, dP/dtmax and dP/dtmin) by increasing RV end diastolic pressures (from 0 to 40 mmHg). P<0.05 was considered significant.In the PE group (n=6), ex vivo RV function was decreased significantly after 5 days compared with the Sham group (n=6), including RV developed pressure (PE, from 14±3.5 to 68±5.1 mmHg) vs (Sham, from 38±1.2 to 88±2.4 mmHg), dP/dtmax (PE, from 516±114 to 1022±201 mmHg/s) vs (Sham, from 1442±113 to 1826±75 mmHg/s), and dP/dtmin (PE, from ‐401±76 to ‐667±108 mmHg/s) vs (Sham, from ‐992±71 to ‐1185±77 mmHg/s). When compared with PE group, Treatment animals (PE+Doxy, n=6) had significantly improved RV function (from 35±4.0 to 89±1.7 mmHg), (from 1411±198 to 2034±149 mmHg/s) and (‐852±126 to ‐1119±87 mmHg/s) respectively.Doxycycline improved the intrinsic RV contractile dysfunction caused by PE. Doxycycline may help preserve RV function and decrease morbidity after PE.
Simultaneous Determination of Microvascular Endothelial Glycocalyx Structure and Albumin Flux in vivo
Authors: Betteridge Kai , Arkill Kenton , Neal Chris , Bates David , Salmon Andrew 
Published: June 2021

Endothelial Glycocalyx coats the luminal surface of all blood vessels and is a key regulator of permeability. We aimed to design a combined confocal‐fluorescent imaging method for assessing structural‐functional relationships between glycocalyx and albumin flux (PsBSA) in systemic mesenteric microvessels of rats in vivo.Mesenteric microvessels were cannulated using double barrel theta style micropipettes and perfused with unlabeled 4% BSA and Alexa Fluor 488 labeled BSA in sequence, which was imaged using fluorescent microscopy to calculate PsBSA. Endothelial glycocalyx depth was then quantified by changing the perfusates to trimethylamino‐diphenylhexatriene (TMA‐DPH: membrane label) and tetramethylrhodamine‐isothiocyanate‐conjugated Wheat Germ Agglutinin (TRITC‐WGA lectin: glycocalyx label), and imaged using Confocal Microscopy. To validate the technique the glycocalyx structure was modulated in real time using neuraminidase or vehicle control.Neuraminidase decreased glycocalyx depth (peak to peak) (p < 0.05, two‐way ANOVA & unpaired t‐test) and its fractional distribution (fractional coverage) (p < 0.05, unpaired t‐test) in a time dependent manner which directly correlated to a paired significant increase in PsBSA in the same microvessels in vivo (p < 0.05 by Pearson's correlation) (p < 0.001 by two‐way ANOVA).We have effectively demonstrated a technique for linking structural estimates of glycocalyx to functional measurements of albumin flux in vivo and our results indicate an activity and time dependent functional response to neuraminidase cleavage of sialoglycoproteins.
Classical Macrophage Activation Decreases The Level of Extracellular MicroRNA‐223 Secreted by Bone‐Marrow‐Derived Macrophage
Authors: Chang Richard , Song Hui , Ying Wei , Splawn Taylor , Zhou Beiyan 
Published: June 2021

Compelling evidence demonstrated that adipose‐tissue‐resident macrophages (ATMs) are critical educators in adipose tissue niche by regulating adipocyte functions. ATMs in obese objects primarily display a classical activation status with pro‐inflammatory features (M1), which is a major shift from ATMs in lean adipose tissues that exhibit mainly anti‐inflammatory profiles (M2). As the major cell compartment in adipose stroma, ATMs exert profound regulatory effects by secreting large amount of molecules upon environmental cues, including various cytokines and chemokines. Recent study suggested that, in addition to protein and peptide molecules, RNAs can also be detected in the extracellular fluid and may function as a new type of cell communicating molecules. However, why these exRNAs are produced and how they function are yet to be determined.To better understand the regulatory mechanism of ATMs on adipose tissue function, we generated exRNA profiles from the conditioned medium from M1 and M2 macrophages. Interestingly, our results revealed that exRNA profiles are distinct from intracellular RNAs. This evidence supports that exRNAs secretion is a novel marker of macrophage secretion. In conclusion, our study provides the first sets of evidence to support that ATMs can regulate adipose tissue function by actively releasing exRNAs acting in a paracrine manner in the context of obesity‐associated metabolic syndromes.
Influence of N‐Acetylcysteine on Apoptosis in White‐Gastrocnemius Muscle of Rats With Chronic Heart Failure
Authors: Martinez Paula , Lopes V , Pagan L , Bonomo C , Gomes M , Oliveira Junior S , Cezar M , Damatto R , Lima A , Fernandes D , Laurindo F , Zornoff L , Okoshi K , Okoshi M 
Published: June 2021

The aim of this study is to evaluate the influence of the antioxidant N‐acetylcysteine (NAC) on apoptosis in skeletal muscle of rats with myocardial infarction (MI)‐induced HF. Methods: MI was induced by left coronary occlusion. Four months later, rats were assigned to three groups: Sham (n=7), MI‐C (MI without treatment, n=9), and MI‐NAC (MI treated with N‐acetylcysteine, 120 mg/kg/day, n=10). Rats with small MI were excluded. Six months after surgery, reactive oxygen species generation was assessed by HPLC analysis of dihydroethidium (DHE) oxidation fluorescent products, 2‐hydroxyethidium (EOH) and ethidium, in gastrocnemius muscle (white portion). Apoptosis was analyzed by quantification of DNA fragmentation using an ELISA kit.ResultsMI size did not differ between MI‐C and MI‐NAC groups (p>0.05; Student's t test). EOH/DHE ratio was higher in MI‐C than in Sham and MI‐NAC (Sham 21.3±4.9; MI‐C 46.3±24.5; MI‐NAC 25.9±10.4 nM/µM/g tissue; p =0.014; ANOVA and Bonferroni). The ethidium/DHE ratio was similar between groups. DNA fragmentation was higher in MI‐C than Sham and similar in MI‐C and MI‐NAC (Sham 1.37±0.48; MI‐C 2.85±1.65; MI‐NAC 2.60±0.92 arbitrary units/g tissue; p =0.045; ANOVA and Bonferroni).ConclusionNAC administration does not attenuate apoptosis in gastrocnemius muscle of heart failure rats.Financial support: FAPESP and CNPq.
Can HSP27 and HSP70 be Used as Biomarkers for Chronic Obstructive Pulmonary Disease Diagnosis?
Authors: Al Kayal Hanine , Abou Abass Hassan , El Sabbah Ahmad , Ramadan Wiam , Khashfe Hassan , Al Kwatly Khalil , Joumaa Wissam 
Published: June 2021

Chronic Obstructive Pulmonary Disease (COPD) is one of the major causes of death worldwide and it is accompanied by increased levels of Heat Shock Proteins (HSPs) and inflammation.The aim of this study was to determine, using Enzyme‐Linked ImmunoSorbent Assay (ELISA) technique, the serum levels of HSP27 and HSP70 in healthy non‐smokers (HNS) and smokers (HS) volunteers and in patients with mild to moderate COPD (COPD I,II), severe to very severe COPD (COPD III,IV) and COPD exacerbation (ECOPD).Our results show that between HNS and HS volunteers no significant effect was observed in serum HSP27 and HSP70 (HNS: HSP27: 1.78±0.11 ng/ml [1.10‐2.15], HSP70: 0.17±0.04 ng/ml [0.02‐0.32]; HS: HSP27: 1.96±0.03 ng/ml [1.73‐2.05], HSP70: 0.13±0.03 ng/ml [0.05‐0.35], n=19). In COPD I, II patients, serum HSP27 and HSP70 were increased by 49% and 141% respectively. However, although no more effect in serum HSP70 was observed in COPD III,IV and ECOPD patients, the serum HSP27 was increased by 24% in COPD III,IV patients (as compared with COPD I,II, n=20) and no more effect was observed in ECOPD patients (as compared with COPD III,IV, n=20).These results suggest that HSP27 and HSP70 can be used as diagnostic biomarkers for COPD. Furthermore, we suggest that HSP27 can also be used as a biomarker for COPD progression.
Internet addiction among students of different countries
Authors: Karp Leonid , Salpynov Zhandos , Akhelova Sholpan 
Published: June 2021

The process of informatization and computerization in the modern society can influence health of the youth.Objectiveto investigate Internet addiction (IA) among university students of 3 countries: Kazakhstan, Uzbekistan, Ukraine.MethodsProblematic Internet Use (PIU) indices were calculated according to 4 scales: social comfort, loneliness, distraction, and impulsiveness. The total number of respondents was 578. We used Student's t‐test, Spearmen's rank correlation coefficient, and the Cronbach alpha coefficient to demonstrate the reliability of our tests.The majority of both male and female students reported using the Internet 5 or more times a week. We detected a statistically significant difference between men and women according to the latter type of activity, where females were more likely to use the Internet for entertainment than males (p<0.05). Only 5.1% of all students had a feeling of euphoria while being on‐line while 40.2% had that feeling only sometimes. There was no significant difference according to gender (p<0.05). We compared the separate categories of the PIU between the students of the universities by gender. Data showed statistically significant differences among men in three out of four categories. The high value of the Spearman rank correlation coefficient testifies about the inverse association connection between the number of answers and their rank. We found higher PIU indices among Kazakhstani students in the category of Social Comfort, in comparison with the students of the Uzbekistani with high PIU indices in the category of Diminished Impulse Control.
Prostaglandin E2 Inhibition Promotes Human Aortic Smooth Muscle Cell Differentiation
Authors: Adedoyin Oreoluwa , Loftin Charles 
Published: June 2021

INTRODUCTIONIn a mouse model of abdominal aortic aneurysms (AAAs) induced by chronic angiotensin II (AngII) infusion, the effectiveness of cyclooxygenase‐2 (COX‐2) inhibition in attenuating AAA progression is associated with maintenance of a differentiated smooth muscle cell (SMC) phenotype. However, the mechanisms responsible for COX‐2‐dependent aortic SMC phenotypic modulation are unknown. Therefore, we assessed the hypothesis that COX‐2 reduces human aortic SMC (hASMC) differentiation by the action of prostaglandin E2 (PGE2).METHODSCultured hASMCs were treated with varying concentrations of AngII, PGE2, or inhibitors of COX‐2 and PGE2 synthetic pathway. The effects of these treatments on the expression of SMC differentiation markers and components of these pathways were examined.RESULTSCOX‐2 inhibition with celecoxib significantly reduced PGE2 levels and increased expression of alpha‐actin (marker of differentiation), whereas exogenous PGE2 treatment reduced hASMC differentiation. AngII treatment resulted in increased protein expression of the inducible PGE2 synthase ‐ microsomal PGE2 synthase (mPGES‐1) and decrease in alpha‐actin. Inhibition of mPGES‐1 and PGE2 by 15‐deoxyPGJ2 resulted in increased alpha‐actin whereas mPGES‐1 knockdown reduced PGE2 synthesis, and promoted hASMC differentiation.CONCLUSIONCOX‐2 inhibition by celecoxib may increase hASMC differentiation by inhibiting production of mPGES‐1‐derived PGE2. Specific inhibition of mPGES‐1 may serve as a potential target for attenuating AAA progression by maintaining a differentiated SMC phenotype.FUNDINGNIH HL083122
Muscle Flap Closures in Spine Surgery
Authors: Price Meghan J. , Tillis Rose , Howell Elizabeth P. , Ramirez Luis , Dalton Tara , Baëta César , Mehta Vikram , Abd-El-Barr Muhammad M. , Karikari Isaac O. , Goodwin C. Rory , Brown David A. 
Published: June 2021

Study Design:
Retrospective cohort study using the National Surgical Quality Improvement Program.

Objective:
The objective of this study was to identify preoperative factors that impact the decision to perform prophylactic muscle flap closure and assess risk factors for wound healing complications in patients undergoing spinal procedures with and without muscle flap closure.

Summary of Background Data:
Prior studies suggest that muscle flap closure following complex spine surgery results in a lower risk of wound healing complications. However, these studies have been limited to single institutions and/or surgeons.

Methods:
The National Surgical Quality Improvement Program database was queried for all patients undergoing spine surgery between 2005 and 2017 with and without concomitant muscle flaps. Preoperative and perioperative variables were extracted. Univariate and multivariate analyses were performed to assess risk factors influencing surgical site infection (SSI) and wound disruption, as well as to delineate which preoperative factors increased the likelihood of patients receiving flap closures a priori.

Results:
Concomitant muscle flaps were performed on 758 patients; 301,670 patients did not receive a flap. Overall 29 (3.83%) patients in the flap group experienced SSI compared to 5154 (1.71%) in the nonflap group (P<0.0001). Preoperative steroid use [odds ratio (OR) 0.5; P<0.0001], wound infection (OR 0.24; P<0.0001), elevated white blood cell count (OR 1.034; P<0.0001), low hematocrit (OR 0.94; P<0.0001), preoperative transfusion (OR 0.22; P=0.0068) were significantly associated with utilization of muscle flaps. Perioperative factors including a contaminated wound (OR 4.72; P<0.0001), the American Society of Anesthesiologists classification of severe disease (OR 1.92; P=0.024), and longer operative time (OR 1.001; P=0.0024) were significantly associated with postoperative wound disruption. In addition, after propensity score matching for these factors that increase risk of wound complications, there was no difference in the rates of SSI between the flap and nonflap group.

Conclusion:
Our results suggest that patients with a higher burden of illness preoperatively are more likely to receive prophylactic paraspinal flaps which can reduce the rates of wound-related complications.