bluuebunny/crossref_metadata_2025_split huggingface dataset:
Process Evaluation of a Youth‐Mentor Led Childhood Obesity Prevention Intervention at Urban Recreation Centers
Authors: Schmall Alexandria M , Trude Angela , Gittelsohn Joel 
Published: November 2023

Urban recreation centers offer potential venues for youth‐led childhood obesity prevention programs in low‐income African‐American (AA) communities. However, little is known about how well such programs have been implemented. Thus, we aimed to examine the implementation of the B'more Health Communities for Kids (BHCK) peer‐mentoring nutrition program through a detailed process evaluation. We used a train‐the‐trainers approach to train Baltimore college and high school students as BHCK youth‐leaders (n=17), able to deliver nutrition education and cooking demonstrations to children (10–14 years old) attending seven recreation centers located in low‐income, food desert neighborhoods in Baltimore, MD. Each nutrition session (n=98) was evaluated through multiple process measures to ensure adequate reach, dose delivered, and fidelity, based on standards set a priori. Dose was determined based on the number of intervention materials (e.g. taste tests, educational handouts) delivered to the target population (4 standards). Fidelity was defined as the number of BHCK intervention sessions at recreation centers and youth‐leaders attending each session (5 standards). Reach identified the extent that the target population was exposed to intervention activities (2 standards). Process evaluation was analyzed using Microsoft® Excel and was scored as a “high” if the process domain met ≥100% of the high standard set, “medium” (50–99.9% of high standard) and “low” (<50% of high standard). Overall, the BHCK youth‐leader program was delivered with moderate to high reach and dose, and moderate fidelity. On average, 9 children attended each interactive session (total youth interaction, n= 912), over 1000 taste tests and giveaways were provided at sessions, and seven youth leaders completed the BHCK program. Given the success of the BHCK peer‐mentoring program, youth‐led programs can offer a feasible approach to addressing childhood obesity in low‐income African American neighborhoods.Support or Funding InformationThis research was supported by the Johns Hopkins Global Obesity Prevention Center (NIH U54HD070725) and NE‐Regional Nutrition Education Center of Excellence.
Maternal low protein diet decreases leptin expression in the brains of the neonatal rat offspring
Authors: Marwarha Gurdeep , Claycombe Kate , Ghribi Othman 
Published: November 2023

Maternal low protein (LP) diets during gestation cause learning and memory impairment as well as cognitive deficits in the neonatal and adult offspring. The cellular and molecular mechanism that mediate the deleterious effects of prenatal exposure to a maternal LP diet on cognitive function is egregiously understood. Leptin, an adipocytokine expressed endogenously in the brain, exhibits pleiotropic effects in the brain and plays an indispensable role in learning and memory, as well as neuronal survival. In this study, we show that prenatal exposure to a maternal LP diet results in the mitigation of basal expression of leptin in the brains of the neonatal rat offspring. Sprague‐Dawley female rats were fed either a 20% normal protein diet (NP) or an 8% low protein (LP) diet inducted at three weeks before breeding and continued for the entirety of the gestation period. Prenatal exposure to a maternal LP diet resulted in reduced leptin expression in the brains of the neonatal offspring that was ascribed to a reduction in the C/EBPα and C/EBPβ – mediated transactivation of the leptin promoter. We further delved into and delineated the upstream molecular mediators and elucidated the role of lower CREB‐mediated transcription of C/EBPα and C/EBPβ that resulted in a reduction of the basal expression of C/EBPα and C/EBPβ leading to a significant attenuation in their transcriptional activities in the brains of the neonatal progeny prenatally exposed to a maternal LP diet. This decrease in transcriptional activity of C/EBPα and C/EBPβ results in the attenuation of the basal leptin promoter activity. Furthermore, maternal LP diet also induces a reduction in the enrichment of the acetylated histones in the nucleosomes that envelope the leptin promoter thereby making it refractory to trans‐activation. Our study unveils a mitigation of leptin expression in the brain as a novel mechanistic insight and a conduit into the deleterious effects evoked by prenatal exposure to a maternal LP diet on cognitive function.Support or Funding InformationThis work was supported by National Institutes of Health, Grant # R01AG0145264, to Dr. Othman Ghribi.
Neither Linoleic Acid nor Arachidonic Acid Promote White Adipose Tissue Inflammation in Fads2−/− Mice Fed Low Fat Diets
Authors: Suitor Katherine , Payne George W , Abdelmagid Salma , Mutch David M , Nakamura Manabu T , Ma David WL 
Published: November 2023

Dietary n‐6 polyunsaturated fatty acids (PUFAs) are widely perceived to promote inflammation and contribute to the development of cardiometabolic disease. However, emerging evidence casts doubt on the relationship between n‐6 PUFAs and inflammation, and suggests that different n‐6 PUFAs may influence this relationship differently. Establishing the roles of individual n‐6 PUFAs in vivo is challenging because linoleic acid (LA, 18:2n6) is endogenously and continuously converted into arachidonic acid (AA, 20:4n6). The fatty acid desaturase 2 gene (Fads2) encodes the rate‐limiting delta‐6 desaturase enzyme necessary for converting LA into AA. The goal of this study was to elucidate the independent effects of the two predominant dietary n‐6 PUFAs, LA and AA, on inflammatory signalling in white adipose tissue (WAT) using Fads2 knockout (Fads2−/−) mice. We hypothesized that LA would not induce WAT inflammation unless it is converted into AA. Male C57BL/6 wild‐type (WT) and Fads2−/− mice (n=8 per diet per genotype group) were fed low‐fat isocaloric diets containing either 7% corn oil w/w (containing ~42% LA) or 7% ARASCO oil w/w (containing ~27% AA) for 9 weeks. WAT gene expression, protein levels, and triacylglycerol (TAG) fatty acid composition were analyzed by qRT‐PCR, Western blots, and gas chromatography, respectively. Fads2−/− mice fed the corn diet had no downstream AA, and reduced GLA (18:3n6) and DGLA (20:3n6), in TAGs compared to their WT counterparts. WT and Fads2−/− mice fed the ARASCO diet had significantly higher levels of AA, DGLA, and GLA in TAGs compared to WT mice fed the corn diet. Estimated delta‐5 desaturase enzyme activity (AA: DGLA ratio) in WAT was reduced in Fads2−/− mice fed the corn diet compared to their WT counterparts (p<0.05), and this was reflected by a 1.6‐fold reduction in FADS1 protein content (p<0.04). No differences in gene expression for common cytokines (e.g. Mcp‐1, Ccl5, Arg1, Nos2) and key regulators of oxylipin production (e.g. Cox‐2, Alox12, Alox15) were detected between WT and Fads2−/− mice fed either diet. WT and Fads2−/− mice fed both corn and ARASCO diets showed no difference in total or phosphorylated STAT3 and p38 proteins. These results suggest that in an unstimulated model neither LA nor AA promote WAT inflammation when consumed as part of a low‐fat diet.Support or Funding InformationThis work was supported by a grant from NSERC.
Effects of α‐Lipoic on mitochondrial function in HepG2 cells under H2O2‐induced oxidative stress
Authors: Tang Xue , Xing Xingan , Xiao Hang 
Published: November 2023

α‐Lipoic acid (LA) is an antioxidant that protects against oxidative stress conditions in variety of cells including HepG2 cells. In the present study, we investigated the effects of LA in the mitochondrial DNA (mtDNA) copy number and energy metabolism in H2O2‐injured HepG2 cells. Cells were pretreated with/without 100 μM/L LA for 96 h, then incubated with 800 μmol/L H2O2 for 4 h. The relative mtDNA copy numbers were measured by Real‐time PCR and corrected by simultaneous measurement of the nuclear DNA. Lactate and NADH‐NAD+ were monitored by transfecting FRET nanosensor Laconic and Peredox. Cellular ATP and acetyl coenzyme A contents were also measured. Additionally, Western blot was used to determine the protein expression of mitochondrial transcription factor A (TFAM) and peroxisome proliferator‐activated receptor‐γ coactivator‐1α (PGC‐1α) protein levels. The results showed that H2O2 treatment decreased mtDNA copy number and damaged mitochondrial energy metabolism for decreasing the generation of acetyl coenzyme A, NADH‐NAD+ and ATP level, and increasing lactate content. 100 μmol/L LA treatment significantly increased mtDNA copy number and cellular ATP content compared with H2O2 group. Moreover, acetyl coenzyme A and NADH‐NAD+ were also significantly enhanced by LA. Furthermore, western blot results indicated that LA upregulated the level of TFAM and PGC‐1α protein. Our findings show that LA inhibited glycolysis and improved tricarboxylic acid cycle and oxidative phosphorylation. LA improved mitochondria energy metabolism may be related to its effect on mtDNA copy number.Support or Funding InformationThe present study was supported by the 12th Five‐Year Plan for for Science and Technology Development (No. 2012BAD33B05).
In ‐ vitro Anti‐Proliferative Analysis of Metformin Hydrochloride on Androgen‐Sensitive (LNCaP) and Androgen‐Insensitive (PC‐3) Human Prostate Cancer Cell Lines
Authors: Adedeji Dolapo , Hinton Brittney , Payne Gloria 
Published: November 2023

BackgroundProstate cancer is one of the diseases worldwide that causes cancer‐related deaths in men. Metformin is an antidiabetic drug that has been in use for over two decades for the treatment of Type II Diabetes mellitus (DM2).PurposeThe aim of this study was to evaluate the anti‐proliferative property of Metformin Hydrochloride on LNCAP and PC‐3 human prostate cancer cell lines.MethodIn vitro anti‐proliferative assay was used to assess the anti‐carcinogenic activity of metformin hydrochloride on androgen‐sensitive, LNCaP and androgen‐insensitive, PC‐3, human prostate cancer cell lines using MTT (3‐[4, 5‐dimethylyhiazol‐2‐yl]‐2,5‐diphenyltetrazolium bromide) assay. Effect of metformin hydrochloride was observed on each cancer cell lines after 72‐ and 120 – hour exposure at μM (0 μM, 3 μM, 5 μM and 8 μM) and mM (0.1 mM, 3 mM, 5 mM and 8 mM) concentrations.ResultsThe average cell death ranging between 20% and 60% was observed when androgen‐dependent, LNCaP, and androgen‐independent, PC‐3, human prostate cancer cell lines were treated with metformin hydrochloride at different concentrations of 3 μM, 5 μM, 8 μM, 0.1 mM, 3 mM, 5 mM, and 8 mM. In PC‐3 cell line, the average cell death percentage was between 21% and 33% at μM concentrations at 72‐ and 120‐hour exposure respectively. The average cell death percentage increases to 53% and 57% after 72‐ and 120 hour exposure respectively at mM concentrations. In LNCaP cell line, the average cell death percentage did not change (25%) at μM concentrations at both 72‐ and 120‐hr exposure. The same trend was observed at mM concentrations. The average cell death percentage did not change at 72‐hour exposure (~47%) and about 49% was observed after 120‐hour exposure of the cell line to metformin hydrochloride.ConclusionThe result of this study showed that metformin hydrochloride displayed cytotoxicity to some extent regardless of whether the prostate cancer cell line is androgen‐sensitive or androgen‐insensitive after 72 and 120 ‐ hour exposure. A stronger effect was observed on the androgen‐insensitive (PC‐3) than on the androgen‐sensitive (LNCaP) prostate cancer cell lines. Therefore, for elderly males diagnosed with diabetes and prostate cancer, metformin may aid in suppressing the cancer growth by serving as a defense mechanism for DM2; thereby reducing the cancer mortality rates in obese men.Support or Funding InformationMaster's Degree Programs at Historically Black Colleges and Universities (MD‐HBCU).Grant Award Number: P382G090002
Cytostatic Effects of Pursatilla (Bai Tu Weng) on Mammary Adenocarcinoma Cell Line (MDA‐MB‐231) Along Multiple Signaling Pathways
Authors: Cho Young , Elias Zeyiad 
Published: November 2023

Pursatilla (Bai Tu Weng in Traditional Chinese Medicine) from the perennial Ranunculaceae family has been a remedy for various inflammatory symptoms and GI disorders. We studied the cytostatic effects of Pursatilla in human mammary carcinoma cells (MDA‐MB‐238) using the whole plant extract. MAPK (mitogen‐activated protein kinase) and PI3K (phoshoinositide 3‐kinase) pathways were analyzed to examine the cytostatic mechanism of Pursatilla action via immunoblotting assay. Mitogenic stimulation by FBS, measured through phosphorylation on MAPK‐42/44 and PKB, was nearly reversed by Pursatilla in MDA238 cell line. In addition, cell cycle progression, specifically the S‐phase entry in mitosis, is blocked by Pursatilla. However, the cell viability assay (trypan blue) and the cell metabolic activity assay (MTT) indicated that the anti‐mitogenic action of Pursatilla was independent of the cytotoxicity. Consequently, we present the cytostatic and anti‐mitogenic action of Pursatilla via MAPK and PI3K pathways in MDA238 cell line.Support or Funding InformationBastyr University Faculty Seed Grant and Student Research Grant.
A Novel Hydrogen Sulfide Prodrug, BW‐HP‐202, Attenuates Myocardial Ischemia/Reperfusion Injury
Authors: Li Zhen , Organ Chelsea L. , Trivedi Rishi K. , Zheng Yueqing , Yu Bingchen , Wang Binghe , Lefer David J. 
Published: November 2023

Background and HypothesisHydrogen sulfide (H2S) protects against acute myocardial ischemia/reperfusion (MI/R) injury and heart failure by ameliorating oxidative stress, improving mitochondrial function, and attenuating apoptosis. One of the major limitations of currently available H2S donors is poor pharmacokinetic profiles that result in very rapid and uncontrolled H2S release. BW‐HP‐202 is a recently developed H2S prodrugs designed for sustained release of H2S upon catalysis in vivo via cellular metabolism. We hypothesized that BW‐HP‐202 would ameliorate myocardial cell death following MI/R in an in vivo murine model.Methods and ResultsMale C57BL/6J mice (10–12 weeks of age) were subjected to 45 minutes of MI followed by 24 hours of R. At the time of reperfusion, animals received BW‐HP‐202 (50 mg/kg, 100 mg/kg) or Vehicle (1% THF) by intracardiac injection. In addition, at 4 hours of R, plasma was collected for troponin‐I measurements. Myocardial infarct size was reduced by 38% (p < 0.05 vs. Vehicle) in mice treated with 50 mg/kg BW‐HP‐202, 45% (p < 0.01 vs. Vehicle) in mice treated with 100 mg/kg BW‐HP‐202. Circulating Troponin‐I levels were also significantly reduced in mice treated with BW‐HP‐202 (41.3 vs. 17.63 vs. 19.86, p < 0.05).ConclusionsBW‐HP‐202 significantly attenuated MI/R injury in a murine model in a dose‐dependent manner. Experiments are currently underway to further define the pharmacokinetics, mechanisms of action, and safety profile of this H2S prodrug.
Protamine Sulfate Neutralization of Bovine and Porcine Heparins: Developmental Implications.
Authors: Paria Sayan , Atcho Omar , Kouta Ahmed , Abro Schuharazad , Hoppensteadt Debra , Jeske Walter , Kingo Jonas , Fareed Jawed 
Published: November 2023

INTRODUCTIONBovine heparins are currently under consideration for the re‐introduction in the US. Protamine sulfate is commonly used to neutralize heparin. Currently, porcine heparin is used for surgical and interventional purposes. The USP Potency of the currently available bovine heparins is lower than that of porcine heparins. This study investigated the differential neutralization of bovine and porcine heparins by protamine sulfate using various laboratory assays.MATERIALS & METHODS8 bovine heparins were obtained from Kin Master, Brazil in powder form with 140–150 U/mg potency. The porcine heparin was obtained from Medefil Inc., U.S.A. in powder form with potency of 190 U/mg. Each of the bovine heparins was supplemented to blood bank plasma at concentrations of 0–10 mg/ml. The effect of protamine sulfate at a fixed concentration of 10 mg/ml was measured using aPTT, thrombin time, amidolytic anti‐Xa and anti‐IIa assays. Saline supplemented heparinized plasmas were used as control. Additionally, the neutralization of the anti‐coagulant effects of a fixed concentration of pooled bovine heparin at 10 mg/ml by protamine sulfate was also studied at a fixed concentration of 10 mg/ml.RESULTSAll 8 bovine heparins produced a concentration dependent prolongation in aPTT and thrombin time assays. Although porcine heparin exhibited stronger anticoagulant effects in these assays. The protamine neutralization profile of both bovine and porcine heparins was similar. Protamine at concentration of 5 mg/ml completely neutralized the equigravimetric amounts of heparins. However, protamine was not effective in neutralizing the higher concentration of these agents. In the amidolytic anti‐Xa assay both heparins produced concentration dependent inhibitory effects, however porcine heparin was stronger. In this assay, protamine differentially neutralized the bovine heparin in comparison to porcine heparin. At 5 mg/ml almost complete neutralization was noted. In the anti‐IIa aminolytic assay, bovine heparins were weaker than porcine heparin. However, protamine sulfate completely neutralized both bovine and porcine heparins. In the whole blood ACT assay at 10 mg/ml, porcine heparin produced stronger anti‐coagulant effect (380 ± 21sec.) in comparison to bovine heparin pool (304 ± 17 sec.). Protamine sulfate at 10 mg/ml, markedly neutralized the anti‐coagulant effects of both heparins. The relative neutralization was comparable between the bovine and porcine heparins.CONCLUSIONSThese studies demonstrate that in the whole blood and plasma based clotting assays the protamine neutralization profile of porcine and bovine heparin is similar when compared at equigravimetric concentrations. However, in the anti‐Xa assays, differences are noted between the two heparins. This may be due to the differential compositions of these heparins at the lower molecular weight component.
Distinct MAP kinase activation patterns of Angiotensin and Cannabinoid systems in SHR astrocytes
Authors: Haspula Dhanush , Clark Michelle 
Published: November 2023

ObjectiveTo determine the effect of exogenous Angiotensin (Ang) II and ACEA, both alone and in combination, on MAP kinase activation in astrocytes isolated from Spontaneously Hypertensive Rats (SHRs) and Wistar rats.BackgroundBy activation of astroglial Ang type 1 receptor (AT1R) and Cannabinoid type 1 receptor (CB1R), Ang II and cannabinoids are able to exert potent effects on proliferation and neuroinflammation. An increase in phosphorylation states of MAP kinases such as ERK and p38, has been linked to several functions in astrocytes. Although crosstalk between the two receptors has been reported by us and several other groups, the consequences of this interaction at the level of MAP kinase activation has not been investigated.MethodsAstrocytes were isolated from the brainstem and cerebellum of Spontaneously Hypertensive Rats (SHR) and normotensive Wistar rats. The cells were treated with 100 nM Ang II or 10 nM ACEA, both alone and in combination, for varying time periods and the extent of phosphorylation was measured using Western blotting.ResultsAng II treatment resulted in greater activation of MAP kinases in brainstem astrocytes, but not cerebellar astrocytes, of SHRs when compared to Wistar rats. ACEA treatement on the other hand, is associated with a greater activation of MAP kinases in brainstem, but not cerebellar, astrocytes of Wistar rats when compared to SHRs. Co‐treatment of Ang II and ACEA resulted in greater activation of ERK and p38, than Ang II or ACEA treatments alone, in brainstem astrocytes isolated from both SHRs and Wistar rats. In cerebellar astrocytes however, co‐treatment did not result in greater activation of MAP kinases than the treatments alone in both rat models.ConclusionGreater MAP kinase activation, by ACEA, in brainstem astrocytes of Wistar rats when compared to SHRs is suggestive of a potential diminished endocannabinoid tone in pathological conditions such as hypertensions. An augmentation of MAP kinase activation by the combination treatment in brainstem astrocytes, but not cerebellar astrocytes, is indicative of a potential dampening of one system by the other in cerebellar astrocytes. Our findings suggest that the crosstalk between AT1R and CB1R may differ depending on the brain area and the underlying pathological condition.Support or Funding InformationNSU HPD: Grant # 335585
Sestrin2 Inhibited the Activation of Hepatic Stellate cells and Liver Fibrosis via Blocking Transforming Growth Factor‐β Signaling
Authors: Yang Ji Hye , Ki Sung Hwan 
Published: November 2023

Hepatic fibrosis results from chronic liver injury and inflammatory responses. Sestrin2 (Sesn2), an evolutionally conserved antioxidant proteins, prevents acute hepatitis and metabolic liver diseases. However, the role of Sesn2 in the pathogenesis of hepatic fibrosis remains obscure. In the current study, we first investigated whether Sesn2 protects fibrogenesis in cultured hepatic stellate cells (HSC) or in chronic carbon tetrachloride (CCl4)‐treated or bile duct ligation (BDL)‐performed mice. Activated primary HSC up‐regulates the levels of Sesn2 protein and mRNA. Transforming growth factor‐β (TGF‐β) also increased Sesn2 expression in cultured HSC, which was due to increased transcription. TGF‐β signaling occurs primarily by activation of Smad proteins and overexpressed Smad3 increased Sesn2 luciferase activity. In silico analysis of the 5′ upstream region of Sesn2 gene identified a putative Smad binding element (SBE) sequence. Deletion of the putative SBE demonstrated in the human Sesn2 promoter was critical for the TGF‐β‐mediated response. Moreover, ectopic expression of Sesn2 reduces epithelial‐mesenchymal transition (EMT) markers, which is accompanied with a marked decrease in SBE luciferase activity and Smad phosporylation. A recombinant adenovirus Sens2 (Ad‐Sesn2) administration presents less severe hepatic injury as supported by decreases in CCl4‐or BDL‐induced ALT/AST levels. Furthermore, Ad‐Sesn2 reduced liver injury and collagen accumulation. Finally, expression of Sesn2 is down‐regulated in the livers from patients with liver cirrhosis or CCl4‐or BDL‐induced hepatic fibrosis mice. Taken together, our findings suggest that Sesn2 protects HSC activation and hepatic fibrosis via antagonizing TGF‐β signaling.Support or Funding InformationThis research was supported by the National Research Foundation of Korea (NRF) funded by the Ministry of science, ICT & Future Planning (No. R13‐2008‐010‐00000‐0)