bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of Dietary Pulses in a Low Glycemic Index Diet on Renal Function in Participants with Type 2 Diabetes Mellitus
Authors: Mejia Sonia Blanco , Ireland Christopher , Augustin Livia S.A. , Vidgen Edward , Kendall Cyril W.C. , Mitchell Sandra , Sahye‐Pudaruth Sandhya , Chiavaroli Laura , Mirrahimi Arash , Bashyam Balachandran , Coveney Judy , de Souza Russell J. , Sievenpiper John L. , Leiter Lawrence A. , Josse Robert G. , Wolever Thomas M.S. , Vuksan Vladimir V.V. , Pencharz Paul B. , Jenkins David J.A. 
Published: November 2023

BackgroundThere is uncertainty in the effects of dietary pulses so far tested. Reducing the glycemic (GI) of the diet using Acarbose, the α‐glucosidase inhibitor, has been shown to be associated with a lower incidence of cardiovascular disease and hypertension in patients with impaired glucose tolerance. Similar dietary maneuvers to lower the glycemic index of the diet using plant protein (e.g. pulses) may be beneficial in people with diabetes.ObjectiveTo determine the effect of a low GI diet through increase pulse consumption, on renal function in study participants with type 2 diabetes mellitus.MethodsWe conducted a secondary analysis of a 12‐week randomized controlled trial in participants with type 2 diabetes mellitus. The intervention was a low GI diet with emphasis on pulses (LGI‐pulse diet, ~190 g/day) versus a high fiber control diet with emphasis on wheat products (HF‐wheat diet). Markers of renal function (urea, creatinine, albumin, albumin/creatinine ratio, blood urea nitrogen, estimated glomerular filtration rate, creatinine clearance, sodium, phosphorus, and potassium) were assessed in those who completed the study and provided 24h urine collections.ResultsWe included 109 participants with type 2 diabetes mellitus who completed the study and provided 24 hr. urine collections, 52 in the LGI‐pulse diet, and 57 in the HF‐wheat control diet. Dietary protein intake (DPI) was not significantly different between diets. The change in urinary urea was positively correlated with the change of DPI (r=0.23, p=0.01) and animal protein (r=0.22, p=0.02), but not with plant protein, No significant changes within and between treatments were seen in markers of renal function. There was a lack of effect seen on markers of renal function despite a significant relation between dietary protein and urinary urea.ConclusionsIncrease in plant protein through increased dietary pulses consumption as part of a low GI diet did not affect renal function in participants with type 2 diabetes mellitus.Trial RegistrationNCT01063361.Support or Funding InformationThis work was supported by ABIP through the PURENet and the Saskatchewan Pulse Growers.
Impact of Folic‐acid Intervention and MTHFRC677T Gene Polymorphism on All‐cause Mortality Associated with Elevated Serum Homocysteine Levels in Chinese Adults with Hypertension
Authors: Xu Benjamin , Kong Xiangyi , Xu Richard , Zhao Min , Song Yun , Zhang Chunyan , Yu Tao , Liu Lishun , Fan Fangfang , Zhang Yan , Qin Xianhui , Tang Genfu , Wang Binyan , Hou Fan Fan , Huo Yong , Li Jianping 
Published: November 2023

BackgroundMortality is one of the most fundamental metrics of population health. The role of nutrition in reducing mortality is of great public health interest. High levels of homocysteine (HHcy, in part, due to low folate intake) are known to increase the risk of cardiovascular diseases. However, data are limited on the longitudinal association of HHcy levels with all‐cause mortality in low folate regions such as China.ObjectiveIn a population with relatively low folate intake and high rate of HHcy, we aimed to test the hypothesis that HHcy is associated with increased mortality and folic acid therapy can reduce the risk of all‐cause mortality associated with HHcy. We also examined whether the effect may be affected by individual MTHFR (a key enzyme involved in Hcy metabolism) gene C677T polymorphism.MethodsWe analyzed the data of 20,702 hypertensive adults (age: 59.6 ± 7.5 years) enrolled in the China Stroke Primary Prevention Trial (CSPPT), with measurements for individual baseline serum total Hcy (tHcy) levels and MTHFR C677T genotypes. These participants were randomized to receive 5‐year, double‐blind daily treatment with 10mg enalapril and 0.8mg folic acid (n=10,348) or 10mg enalapril alone (n=10,354). Kaplan‐Meier survival analysis and Cox proportionate hazard model were used to estimate the effect of tHcy levels on all‐cause mortality and to test effect modification by folic acid intervention and MTHFR C677T genotype.ResultsThere were 622 (3%) all‐cause deaths during a mean treatment period of 4.5 years. There was a dose‐response relationship between tHcy quartiles and all‐cause mortality (P for trend<0.001) after adjusting for pertinent covariables. This relationship was stronger among participants with CC or CT genotypes than among those with TT genotype. Compared to the enalapril alone group, enalapril plus folic acid therapy further lowered the risk of all‐cause mortality associated with increased tHcy levels. The risk reduction was more pronounced in participants with CC or CT genotypes.ConclusionsIn this large‐scale study of population residing in a low folate region, we found that baseline tHcy levels were associated with all‐cause mortality in a dose‐response fashion; and folic acid therapy can lower the all‐cause mortality risk associated with HHcy. Our data suggest that tHcy and MTHFR genotypes may serve as biomarkers for risk stratification and folic acid therapy may offer a simple, inexpensive and safe intervention strategy to reduce mortality among population characterized by low folate intake and high rate of HHcy.
ATF3 as an Important Factor of the Acute Phase Lung Inflammatory Response in an Animal Model
Authors: Caruso Carla Romina , Cabello Noe , Sinha Utkarshna , Ekpa Ndifreke , DiAngelo Susan , Chroneos Zissis , Silveyra Patricia 
Published: November 2023

BackgroundGround level ozone, an oxidative photochemical air pollutant, is highly corrosive and once inhaled triggers acute lung inflammation, leading to damage of bronchioles and alveoli, and compromising the innate pulmonary immunity. Our previous research has indicated that the expression of lung pro‐inflammatory chemokines and cytokines, such as Interleukin‐6 (IL‐6), are increased after ozone exposure. Since the activating transcription factor 3 (ATF3) is a known regulator of IL‐6 in other models, in this project we sought to determine whether ATF3, via IL‐6, affects and/or modify the lung acute inflammatory response in an experimental animal model.MethodsMale wild type (WT, n=6) and ATF3 knockout (ATF3‐KO, n=5) mice were exposed to 2ppm ozone or filtered air (FA, control) for 3 hours. Lung tissue was collected 4 hours after exposure, and bronchoalveolar lavage fluid (BAL) was obtained 24h post exposure. Total RNA form lung tissue was extracted and retro‐transcribed to measure mRNA levels of IL‐6 by Real Time PCR. Changes in cell counts were evaluated by BAL cytospin analysis, and the expression of the lung injury marker lipocalin‐2 was determined by ELISA in BAL.ResultsThe expression of IL‐6 mRNA was significantly increased by ozone in both WT and KO mice (p<0.05). The lungs of ATF3‐KO mice expressed higher levels of IL‐6 than WT mice, when exposed to FA (10‐fold) or ozone (4‐fold). Moreover, in response to ozone, ATF3‐KO mice expressed significantly higher IL‐6 levels than WT mice (4‐fold, p<0.05). In the BAL, we found an increase in lipocalin‐2 expression in response to ozone, as well as a highly elevated neutrophilic count in ATF3‐KO mice exposed to both FA (23% of total BAL cells) and ozone (40% of total cells) vs. the WT groups (0.2% in FA, 6% in ozone).ConclusionOur preliminary results indicate that ATF3 is an important factor that mediates the lung inflammatory response to acute ozone exposure. This is reflected by the increased levels of acute inflammatory phase cytokines (IL‐6) and cells (neutrophils). Future studies will evaluate the specific mechanisms involved in this response, as well as potential sex differences when including female mice.Support or Funding InformationBIRCWH K12HD055882
Genistein alleviates testicular ischemia and reperfusion injury‐induced spermatogenic damage and oxidative stress by suppressing abnormal testicular matrix metalloproteinase system.
Authors: Al‐Maghrebi May 
Published: November 2023

The aim of the study is to examine the role of Matrix metalloproteinases (MMPs) and their inhibitors (TIMP) during testicular ischemia/reperfusion (t I/R), the involvement of the Notch pathway, and their modulation by the antioxidant, Genistein. Three groups of male Sprague– Dawley rats were used: sham rats, tI/R rats, and genistein‐treated rats (10mg/Kg). The t I/R rat model underwent testicular artery occlusion of the left testis and was subjected to 60 min ischemia followed by 4 h reperfusion. Protein expression of MMP‐2, MMP‐9, TIMP‐1, and TIMP‐2 were measured in testicular tissue. Histological examination was performed to assess spermatogenesis. Protein levels of Notch 2, Jagged 1, and hairy/enhancer of split 1 (hes‐1) was quantified. The degree of testicular oxidative stress, DNA damage and germ cell apoptosis were also evaluated. t I/R induced severe tubular damage, a significant increase in MMP‐2 and MMP‐9 expression and decreased expression TIMP‐1 and TIMP‐2. Genistein treatment normalized the MMP‐TIMP imbalance. Rats subjected to t I/R had low total antioxidant capacity of the testis, decreased superoxide dismutase activity, and increased oxidative DNA damage. Enhanced activities of caspase 8, caspase 3 and PARP were also observed during t I/R. Genistein suppressed the t I/R‐induced activity of the Notch 2/Jagged 1/hes‐1 pathway. Genistein was also able to salvage the testicular structure and function through restoring the MMP‐TIMP anti‐proteolytic balance, suppressing spermatogenic damage, alleviating oxidative stress and apoptosis. The Notch pathway is partly involved in inhibiting the t I/R‐induced testicular impairment.Support or Funding InformationThis study was supported by Kuwait University Research Grant SRU02/13.
Amphiregulin Promotes Fibroblast Activation in Pulmonary Fibrosis
Authors: Liu Tianju , De Los Santos Francina Gonzalez , Ding Lin , Wu Zhe , Phan Sem H 
Published: November 2023

Amphiregulin (AREG), an epidermal growth factor receptor ligand, is implicated in tissue repair and fibrosis by recent studies. Group 2 innate lymphoid cells derived AREG is reported to be important for the epithelial integrity, and involved in repair of airway epithelium following injury. However AREG is essential for pulmonary fibrosis induced by TGFβ overexpression, and its deficiency significantly impairs bleomycin‐induced pulmonary fibrosis. AREG is significantly induced in BLM‐induced fibrotic lung tissues primarily in bone marrow‐derived CD11c+ cells that play a significant role in promoting lung fibrosis. Moreover recombinant AREG stimulates mouse lung fibroblast proliferation accompanied by the induction of telomerase reverse transcriptase (TERT) expression. To further elucidate the possible mechanism by which AREG activates fibroblasts during the development of pulmonary fibrosis, its direct role in fibroblast proliferation and motility was investigated. The results showed that AREG significantly increased human lung fibroblast proliferation. The response to AREG was significantly enhanced in the telomerase expressing lung fibroblasts from an IPF patient compared to telomerase negative cells from control subjects. To assess the importance of induced TERT expression in the AREG‐induced cell proliferation, the effect of TERT overexpression was investigated in the human BJ fibroblast cell line. In response to AREG treatment, BJ5ta cells with stably transfected hTERT exhibited significantly greater proliferation relative to control BJ cells. Conversely, significant reduction of AREG‐induced cell proliferation was noted in TERT deficient fibroblasts. Thus induction of TERT by AREG significantly enhanced fibroblast proliferation. Moreover AREG caused significantly increased lung fibroblast motility in an in vitro scratch assay, which was associated with increased expression of α6 integrin. Finally lung α6 integrin mRNA was highly induced in bleomycin‐induced pulmonary fibrosis, which was significantly diminished in AREG deficient mice. Thus AREG‐induced cell motility might be associated with the induction of α6 integrin expression. Taken together, these findings indicated that AREG‐induced fibroblast activation, motility and invasiveness may contribute to the increased number of fibroblasts in pulmonary fibrosis.Support or Funding InformationThis study is supported by NIH grants HL052285, HL091775 and HL112880.
Epigenetic signatures of alcohol abuse in hepatocellular carcinoma
Authors: Puszyk William Matthew , Hlady Ryan , Robertson Keith , Cabrera Roniel , Liu Chen 
Published: November 2023

There is a paucity of human in vitro models available to study the effects of alcohol in hepatocellular carcinoma (HCC). HCC cell lines are often deficient in either alcohol dehydrogenase (ADH) or cytochrome P450 2E1 (CYP2E1). VL‐17a is currently the most widely studied model available. VL‐17a is derived from a HepG2 cell line engineered to overexpress mouse ADH and human CYP2E1. LH86 is a novel HCC cell line previously developed in our laboratory.Here we compare the LH86 cell line with the current model to identify a novel tool to study the effects of alcohol in HCC.The aim of this study is to evaluate the LH86 cell line as a novel human in vitro model to study the effects of alcohol in HCC. The cell lines were cultured with alcohol and gene expression and epigenomic changes were identified.The LH86 cell line was observed to have unique functional properties indicating that it is a potential novel tool to study the effects of alcohol in HCC.Support or Funding InformationR01 AA19976 TO KR AND CL
Androstenetriol enhances lung macrophage host defense against bacterial pneumonia in mice
Authors: Kobzik Lester , Yang Zhiping , Lu Peng , Mo Fengfeng , Loria Roger 
Published: November 2023

The active metabolite of dihydroepiandrosterone, 17beta‐androstenetriol (AET), has potent immunomodulatory effects but its potential to improve host defense against the common problem of bacterial pneumonia has not been studied. Mice (C57BL/6, male) were pre‐treated with AET (0.5 mg, s.c.) or vehicle before infection with Strep. pneumoniae (serotype 3, 100K CFU, i.n.). Evaluation showed 8‐fold improved bacterial clearance at 24 h (p <.001, n>20/group) accompanied by decreased inflammation (5‐fold fewer neutrophils in lung lavage samples at 24 h, p < .001). Secondary bacterial pneumonia after influenza remains a major clinical problem. AET treatment of mice on day 7 after non‐lethal influenza infection produced resulted in 15‐fold improved bacterial clearance (p <.001, n >5/group). Survival analysis showed 37% survival in AET‐treated vs. 0% survival in vehicle‐treated mice in this model of secondary pneumococcal pneumonia. In vitro, AET improved macrophage killing of bacteria in vitro (e.g. % bacteria alive after ingestion, vehicle vs AET‐treated: 54 ± 8 vs. 36 ± 7, n>5). To explore mechanisms, we analyzed the role of MARCO, a macrophage scavenger receptor with important functions in host defense against bacteria. Western blot analysis showed that in vitro AET increased MARCO expression in both murine and human macrophages. Comparison of bacterial clearance after vehicle or AET pre‐treatment showed marked improvement in wild‐type mice, but no benefit in MARCO −/− mice. We conclude that AET enhances innate resistance to primary and secondary pneumococcal pneumonia, in part through increased expression of the scavenger receptor MARCO, and is a potential immunomodulator for improving lung host defense against bacterial pneumonia.Support or Funding InformationNIH ES00002 ES11008
Hepatic stellate cells play an essential role in acetaminophen‐induced hepatocyte injury with or without prior endotoxemia
Authors: Rani Richa , Tandon Ashish , Kumar Sudhir , Gandhi Chandrashekhar R 
Published: November 2023

Acetaminophen (APAP)‐induced liver injury is augmented by gram‐negative bacterial endotoxin (lipopolysaccharide: LPS). However, the understanding of the mechanisms of this clinically significant problem and the early predictors of cellular stress/injury is inadequate. LPS‐stimulated perisinusoidal hepatic stellate cells (HSCs) produce an array of cytokines that can affect survival of hepatocytes. The aim of this study was to investigate the role of LPS‐stimulated HSCs in augmenting APAP‐induced liver injury. Rats (n=6 each) were administered 5 mg/kg LPS or vehicle (PBS) (i.p.), followed by 200 mg/kg APAP or PBS (i.p.) 1h later, and sacrificed at 6h. Control rats received PBS at both time points. LPS and APAP alone induced mild liver injury, endoplasmic reticulum (ER) stress and autophagy as demonstrated by histologic examination, electron microscopy, increased CHOP expression and LC3‐II formation, and caspase‐3 activation. Augmentation of liver injury occurred when the rats were administered LPS and APAP. While CHOP expression and caspase‐3 activation increased further with LPS+APAP than with LPS or APAP, autophagy did not show significant change over that due to APAP alone. Notably, the liver injury was accompanied by proportionate increases in the serum levels of hepatocyte survival factor “augmenter of liver regeneration (ALR)”. In vitro, addition of APAP to hepatocytes incubated in LPS/HSC‐conditioned medium inhibited DNA and protein synthesis, and increased autophagy (LC3 II expression) and apoptosis (TUNEL staining). LPS‐stimulated HSCs expressed interferon‐β (IFNβ), and LPS/HSC ± APAP‐induced hepatocyte apoptosis was prevented by anti‐IFNβ Ab. Furthermore, consistent with the in vivo effects, LPS and APAP both stimulated secretion of ALR by hepatocytes, which increased strongly when hepatocytes incubated in LPS/HSC‐conditioned medium were challenged with APAP. Finally, HSC‐depleted mice were found to be protected from excessive liver injury due to APAP (600 mg/kg) treatment for 6h as well as LPS (5 mg/kg overnight) followed by 600 mg/kg APAP administration. These results suggest that HSCs play a critical role in causing liver injury due to APAP alone and in the presence of endotoxemia, and thus contribute to acute liver failure. The data also suggest that serum ALR can be a reliable diagnostic marker for hepatocyte stress or injury.Support or Funding InformationVA Merit Review grant 1IO1BX001174‐01A1
Cell‐specific Wnts regulate liver zonation and regeneration
Authors: Preziosi Morgan , Yang Jing , Okabe Hirohisa , Diegel Cassandra , Williams Bart , Monga Satdarshan 
Published: November 2023

Our lab has previously shown that β‐catenin regulates liver regeneration in a partial hepatectomy (Phx) model, under the control of Wnt and the canonical signaling pathway. This is true at early timepoints up to 40–72 hours. Using cell‐specific Wntless (Wls) knockout mouse models, we have previously determined epithelial cells are not the source of these Wnts. However, macrophage‐specific Wls knockouts (MP‐KO) have a regeneration deficit at 40 hours that is not seen earlier, suggesting they are a contributing source of Wnts in a temporal manner. We sought to further elucidate the source, identity, and initiation of Wnts using a Tamoxifen‐inducible endothelial cell‐specific Wls knockout model (EC‐KO). At basline, EC‐KO showed decrease in pericentral b‐catenin target genes such as GS, Cyp2e1, and notably Cyclin D1, suggesting a contribution to zonation and potentially regeneration. Since b‐catenin activation occurs early during regeneration, we also wanted to investigate the most proximal event that could be stimulating Wnt expression and secretion from relevant cells after hepatectomy. We hypothesized that shear stress immediately after Phx may initiate Wnt expression and secretion. Using an in vitro system, a preliminary analysis demonstrates that shear stress can initiate Wnt expression in EC, but not in MP or hepatocytes. In vivo, MP and EC demonstrate high levels of Wnt2 and 9b at baseline, which significantly increases after Phx. Taken together, we predict shear stress initiates secretion of Wnt2 and Wnt9b from EC at early timepoints, and MP secrete Wnt2 and Wnt9b at later timepoints, thus temporally regulating b‐catenin and contributing to liver regeneration.Support or Funding Information5T32HL094295‐05
Spatial Abilities and Pictures of Objects Recognized from Haptic Perception: Effect of Short Term Memory
Authors: Langlois Jean , Dagenais Yvan , Martin Marcel , Lemieux Renald , Lecourtois Marc , Yetisir Elizabeth , Bellemare Christian , Bergeron Germain , Hamstra Stanley J. , Wells George A. 
Published: November 2023

ObjectiveAs a basis for an application in anatomy education, vision‐based spatial abilities tests have been correlated with pictures of objects recognized from haptic perception. The objective of the current study was to determine the effect of short term memory on the recognition of pictures of objects from haptic perception. The hypothesis is that the use of short term memory has a negative effect on the performance.MethodsA cohort of 48 medical graduates was enrolled in a prospective study. Ethics committee approval and written informed concent were obtained. Spatial abilities were measured with a redrawn Vandenberg and Kuse Mental Rotations Tests in two (MRTA) and three (MRTC) dimensions and a Surface Development Test (SDT). In a one‐month rotation preparing for residency, the experiment was done within a one‐week drawing course before a one‐week applied anatomy course. Twenty‐five objects constructed from various shaped parts glued together were identified on a picture by participants after haptic perception. In the first exercise, participants could touch the object for up to two minutes while identifying the corresponding picture. In the second exercise, 30 seconds were allowed for haptic perception of the object, 15 seconds to memorize, and up to 75 seconds to identify the corresponding picture without any further haptic access to the object. The maximum score was 24 for each of MRTA and MRTC, 60 for SDT, and 25 for the picture score. Descriptive statistics included median and lower and upper quartiles. Spearman's correlation coefficient was used to correlate the picture score to MRTA, MRTC and SDT scores. Wilcoxon signed‐rank test was used to compare the picture score in the first and second exercise.ResultsThe picture score in the first exercise [18 (12, 21)] was correlated with MRTA [14 (9, 17)], MRTC [9.5 (6.5, 12)] and SDT [44.5 (36, 53)] scores with a correlation of 0.427 (p = 0.0025), 0.539 (p < 0.0001) and 0.429 (p = 0.0024), respectively. Similarly, the picture score in the second exercise [10 (7, 13)] was correlated with MRTA, MRTC, and SDT scores with a correlation of 0.444 (p = 0.0014), 0.384 (p = 0.0064) and 0.323 (p = 0.0236), respectively. The picture score in the first and second exercise was different (p < 0.0001).ConclusionHaptics is involved in the handling of anatomical structures. Vision‐based spatial abilities tests were correlated with pictures of objects recognized from haptic perception. The use of short term memory was found to have a negative effect on the performance. These findings on haptic perception and short term memory have promising avenues for education in the anatomy laboratory.Support or Funding InformationThis study was supported by an internal grant from the Department of Surgery, Université de Sherbrooke, Sherbrooke, QC, Canada.