bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of dietary sugar intake with bone loss, non‐traumatic fracture risk, and all‐cause mortality in Chinese elderly: finding from an 11‐year longitudinal study of Mr and Ms OS Hong Kong
Authors: Liu Zhaomin 
Published: November 2023

BackgroundThe association of dietary sugar intake and skeletal health remains uncertain, especially among elderly. Our objective was to investigate sugar consumption in Chinese elderly and the temporal association of sugar intake with bone health and mortality.MethodsAnalyses were conducted based on an 11‐year longitudinal study (Mr and Ms OS Hong Kong). A total 4000 Chinese men and women aged 65 and older were recruited from the local community from 2001 to 2003. The study consisted of a 4‐year follow‐up (n=3416) on the changes in bone mineral density (BMD) and an 11‐year follow‐up for the incidence of non‐traumatic fracture and all‐cause mortality (n=3344). Free and added dietary sugar intakes were assessed at baseline using a 329‐item validated Food Frequency Questionnaire. BMD was examined at baseline and 4‐year follow‐up by dual‐energy X‐ray absorptiometry at total hip, spine, femoral neck and whole body. Data on the incidence of non‐traumatic fractures and all‐cause mortality were collected. General linear model, logistic, and Cox proportional hazards models were used to test the associations of sugar intakes with bone health and all‐cause mortality.ResultsThe average free sugar intake among the participants was 20.0±19.8 g/d (4.16±3.57% calories) with only 5.4% exceeding the WHO recommendation (<10%). During a median follow‐up of 11.1 years (34,483 person years), we documented 433 non‐traumatic fractures and 769 deaths. No significantly association was observed between total free and added sugar intakes with BMD changes, as well as the incidence of non‐traumatic fracture. However, high sugar intakes were significantly associated with low risk of all‐cause mortality in elderly women with hazard ratios of 0.625 (95% CI: 0.428–0.915, p for trend: 0.033) for free sugar and 0.578 (95% CI: 0.386–0.867, p for trend: 0.004) for added sugar in the highest quintile compared with that in the lowest quintile.ConclusionsThe amount of sugar consumed by Chinese elderly pose no risk to bone loss and fracture. High sugar intakes were even associated with low all‐cause mortality in elderly women.Support or Funding InformationThe study was supported by the National Institutes of Health R01 grant AR049439–01A1 and the Research Grants Council Earmarked Grant CUHK4101/02 M. The funders played no role in the study design, data collection and analysis, interpretation of the data, as well as in writing the manuscript.
Are Meals and Snacks Consumed by Preschool‐aged Children in Family Child Care Homes Meeting the Dietary Guidelines?
Authors: Tsai Maggie You Ming , Mena Noereem Z , Gans Kim M , Risica Patricia M , Lofgren Ingrid E , Tovar Alison 
Published: November 2023

Although family child care homes (FCCH) are the second most utilized form of non‐relative child care in the US, little is known about what children eat in this setting. The objective of this study was to assess the quality of meals and snacks consumed by children aged 2–5 in FCCH compared to the 2015 Dietary Guidelines for Americans (DGA 2015). This study used baseline data from an ongoing cluster randomized controlled intervention trial in FCCH. Preschool‐aged children (n = 104; 2–5 years old) enrolled in 34 FCCH, were observed during two meals and a snack each day for two days, following a standardized protocol. Foods and beverages consumed were analyzed in the Nutrition Data System for Research 2015. Mean portion sizes consumed of each food group were compared to 2/3 of the daily intake recommendations established by the DGA 2015 for children 1–3 years old (1000 kcal) as recommendations are not standard for children 2–5 years old, proportional to the daily nutrient requirements for time spent in childcare. One‐sample t‐tests were run to test for differences between the mean amounts of food groups consumed compared to the national guidelines. Mean intakes of children did not meet the recommended 0.67 cup of vegetables (0.27 ± 0.21 cup, 40% of recommendation), 1.0 ounce of whole grains (0.37 ± 0.37 ounce, 37% of recommendation), and 14 grams of fiber (5.60 ± 2.14 gram, 40% of recommendation). However, children were close to meeting the recommended 0.67 cup of fruit (0.64 ± 0.46 cup, 97% of recommendation). Generally, children in this FCCH study did not meet national recommendations for vegetables, whole grain, and fiber. Future research should continue to develop and evaluate strategies to increase fruit, vegetable and whole grain intake in early child care settings.Support or Funding InformationThis project was supported by the National Heart, Lung, And Blood Institute of the National Institutes of Health under Award Number R01HL123016
Genetics of acute kidney injury markers in Hispanic children: the Viva La Familia Study.
Authors: Vazquez‐Vidal Itzel , Chittoor Geetha , Mass Baba , Haack Karin , Laston Sandra , Mehta Nitesh , Comuzzie Anthony G , Cole Shelley , Butte Nancy , Voruganti V. Saroja 
Published: November 2023

Studies have demonstrated that chronic kidney disease in adults may develop from acute kidney injury during childhood. Thus, increases in acute kidney injury (AKI) markers that are indicative of sharp decline in kidney function are a cause of concern for later kidney disease. AKI markers are also under considerable genetic influence. Our aim in this study was to identify genetic determinants of urinary AKI markers: neutrophil gelatinase‐associated lipocalin (NGAL), cystatin C (CysC), beta‐2‐microglobulin (β2M), osteopontin (OST) and trefoil‐factor 3 (TFF3) in Hispanic children of the Viva La Family Study. Urinary concentrations of NGAL, CysC, β2M, OST and TFF3 were measured in 837 children. We conducted a genome‐wide association analysis of AKI markers after accounting for family kinships. All methods were implemented in SOLAR. Empirical thresholds for genome‐wide significant and suggestive associations were defined as p <1 × 10−7, and p <1 × 10−6, respectively. Significant heritabilities were found for all AKI markers (range 35 – 68%), with CysC showing the highest heritability (h2= 0.68, p= 1.9×10−15). The GWAS analysis showed strong association of rs7555367 of phospholipid phosphatase related 5 (PLPPR5) gene with OST (p = 3.5 × 10−8, MAF = 0.09, β coefficient = −0.58 (0.10)) and suggestive association with TFF3 and β2M (p < 2.7 × 10−6, MAF = 0.09, β coefficient = −0.48 and −0.55 (0.11)). We also found suggestive association between OST and 8 SNPs (rs10169879, rs10210408, rs16856600, rs2075252, rs2284675, rs2389589, rs3821125, rs4668123) in lipoprotein‐related protein 2 (LRP2)/megalin gene (p < 3 × 10−7) and between NGAL and rs12947457, rs7216231 and rs4968239 of N‐ethylmaleimide sensitive factor, vesicle fusing ATPase (NSF) (p < 3.4 × 10−7). These genes have key roles in cell signaling and signal transduction. In summary, we observed significant genetic influence on the variation in AKI markers and identified a potential role for PLPPR5, LRP2 and NSF in AKI in children.Support or Funding InformationThe National Institutes of Health (NIH) [R01DK080457, R01MH59490, P30ES010126 and R01DK092238] and the USDA/ARS [Cooperative Agreement 6250‐51000‐053].
Casein before bed is as effective as receiving earlier in the day in increasing muscle mass and strength in response to resistance training
Authors: Joy Jordan , Vogel Roxanne , DiMarco Nancy , Broughton Ken , Wildman Rob 
Published: November 2023

Amino acids from food directly initiate muscle protein synthesis and recent studies support that this process is not altered during sleep. This opens the concept of ingesting protein before bed as part of a greater strategy to maximize effects of resistance training with protein throughout the 24‐hour period. The purpose of this study was to investigate the response of supplemental protein (casein) provided earlier in the day versus before bed when resistance training occurred before 4pm. Young males (19–24 yoa) engaged in supervised resistance training with nutrition guidance and either received casein protein (35g) earlier in the day or before bed for 10 weeks in an isocaloric and nitrogenous design. Data were analyzed using repeated measures ANOVA with Bonferroni post‐hoc. Both groups demonstrated increases in lean soft tissue and strength (p < 0.05) with no difference between groups. No changes were observed for measures of body fat. Providing protein before sleep is an effective time to incorporate protein as part of a 24‐hour strategy, even if the training occurs earlier in the day.Support or Funding InformationSupported by Dymatize Nutrition
Rifampicin and Isoniazid Induced Liver Injury via the Pregnane X Receptor
Authors: Brewer Christopher Trent 
Published: November 2023

BackgroundDrug‐induced liver injury (DILI) is a significant cause of anti‐tubercular therapy failure. Rifampicin and isoniazid co‐treatment have been shown to lead to cholestatic liver injury associated with the accumulation of protoporphyrin IX (PPIX, a heme precursor) in a human pregnane X receptor (hPXR) dependent manner in mice. Therefore, the activation of hPXR by rifampicin can lead to DILI via PPIX accumulation, thus antagonism of hPXR and modulation of PPIX transport and degradation can prevent the clinical consequences of DILI.ObjectiveUsing an hPXR mouse model and primary human hepatocytes we will induce liver toxicity and evaluate the potential of a novel small molecule inhibitor of hPXR developed by our laboratory to prevent liver injury and Mlkl activation associated with rifampicin and isoniazid treatment.MethodsPPIX accumulation was assessed by fluorescence and LC/MS/MS in human cell lines and humanized transgenic mice. hPXR target gene expression was evaluated using Western Blot and qRT‐PCR analyses in human primary cells and humanized mice. Liver injury was evaluated by analyzing mouse liver enzyme activity in sera and via histopathologic examination.ResultsALAS1/Alas1 (rate‐limiting enzyme of heme synthesis) is increased in response to isoniazid in both hPXR transgenic mice and PXR knockout mice. FECH/Fech (heme synthesis enzyme) is reduced in response to isoniazid in both mouse strains. PPIX is increased in the liver of hPXR mice treated with both rifampicin and isoniazid. Rifampicin and isoniazid co‐treatment activate necroptosis markers in hPXR mice.ConclusionsAntagonism of hPXR with a small molecule may be a viable therapeutic strategy to reduce liver injury.Support or Funding InformationFunding provided by ALSAC and NIGMS (GM 086415 & 110034)
Regulation of extracellular matrix gene expression and biosynthetic pathways in pulmonary fibroblasts by HSF1
Authors: Jones Mikayla , Wales Christina TK , Gristock Rachel A , Jacobs Aaron T 
Published: November 2023

Idiopathic pulmonary fibrosis (IPF) is a chronic and rapidly progressing lung disease that is characterized by extensive tissue remodeling, impaired gas exchange, and a poor prognosis. The pathogenesis of IPF involves epithelial cell death, leukocyte infiltration and cytokine production, enhanced deposition of collagen and remodeling of the extracellular matrix (ECM). One key event in the progression of IPF is the activation of fibroblasts that is mediated by TGF‐beta, which leads to tissue remodeling. We have investigated a possible role for the transcription factor, heat shock factor 1 (HSF1) in the expression of pro‐fibrotic genes in TGF‐beta treated fibroblasts. siRNA was used to silence the expression of HSF1 in pulmonary fibroblast cell lines, MRC‐5 and IMR‐90. Cells were treated with TGF‐beta for 0, 8, and 24 h, after which RNA and protein samples were collected. RNA samples were analyzed by real‐time PCR to assess differences in the expression of several target genes with known roles in the production and remodeling of ECM, and results were verified by Western blot. Silencing HSF1 altered the expression of several ECM‐related genes in both cell lines, indicting role for HSF1 in the control of ECM biogenesis and remodeling by TGF‐beta stimulated fibroblasts, and a possible significance for HSF1 activity in the etiology of IPF. In addition to components of fibrillar collagen (COL1A1, COL1A2), the expression of several genes that function in the biogenesis of collagen fibers also were impaired by HSF1 silencing, including proteins with proline hydroxylase (P4HA2), lysyl hydroxylase (PLOD1), prolyl isomerase (FKBP4); and chaperone activities (SERPINE1, SERPINH1). In contrast to its effects on fibrillar collagen biogenesis, HSF1 silencing enhanced the expression of genes involved in elastic fibers production, including: elastin (ELN) microfibrillar‐associated protein 4 (MFAP4); and fibulin 5 (FBLN5). This observation is consistent with the finding by others that the ratio of collagen and elastin fibers is altered in IPF, further indicating a unique role for HSF1 in controlling the composition of the ECM in this disease.Support or Funding InformationFunding provided by the Leahi Fund of the Hawaii Community Foundation
Lack of effect of the direct renin inhibitor aliskiren on cardiac mast cells and macrophages in an acute model of fat embolism in rats
Authors: Fotouhi Ariana , Arif Dauod , Siddiqi Ahsan , Ponnapureddy Rakesh , VanDillen Michael , Tappeta Kathyayiri , Khan Sultan , Hamidpour Soheila , Poisner Alan , Molteni Agostino 
Published: November 2023

IntroductionFat embolism (FE) induced by triolein injection causes both acute and chronic lung injury in rats and the histopathological damage is not limited to the lungs but also involves the heart (1). The renin‐angiotensin system (RAS) plays a role in the pathogenesis of such damage. Captopril and losartan treatment prevented such damage both in lungs and heart at 10 weeks after triolein injection (2). More recently we reported that the renin inhibitor aliskiren induced the same protective effect in the lungs (3) and reduced the number of mast cells 48 hours after triolein (4). The hearts of the same triolein treated rats however had a modest but statistically significant increase of alpha‐smooth muscle actin (SMA) (p<0.05) versus controls but no fibrosis or vasculitis and no changes by aliskiren in the acute experiment. We measured the mast cells and the macrophages in the heart to delineate their potential role in this early cardiac damage.MethodsTwenty‐two rats were divided into controls (n=4, Group A) and three FE groups (n=6, groups B,C &D). FE induction was done with triolein 0.2 ml i.v at 0 hours, and an hour later animals received 0.2 ml i.p saline (Groups A&B), aliskiren at 50 mg/kg (group C) or at 100 mg/kg (Group D). Rats were euthanized at 48 hours and hearts were fixed and stained with H&E for lumen patency measurements, Masson's Trichrome (MT) for collagen, and SMA for myofibroblasts. Mast cells were stained with CD 117 and macrophages with CD 68.ResultsAs reported above, the only damage in the heart of rats treated with triolein and saline was an increase in SMA staining around the branches of the coronary arteries compared to the control group. No other significant difference was observed for all the other parameters. Mast cells and macrophages did not show any statistical difference among the four groups. The macrophages did not show the two types of cells that we have observed in the lungs, one with large cytoplasm with small vacuoles and the second with small compact cytoplasm (5).ConclusionDespite the significant cellular response in the lungs at 48 hours after triolein, there were no alterations in mast cells or macrophages in the heart after triolein or aliskiren treatments. In contrast to the lungs, where we have observed two types of macrophages, only one type was present in the heart. The lack of change in mast cells and macrophages in the heart and no fibrosis with only a modest change in SMA at this early time suggests that their involvement may be limited to later responses to fat embolism.Support or Funding InformationSupported by Mary Katherine Geldmacher Research Foundation, St Louis MO.
Preliminary data on the effects of high fat diet, olive oil and vitamin D on fatty liver and muscle in an experimental model
Authors: Trovato Francesca M , Musumeci Giuseppe , Szychlinska Marta , Nsir Houda , Magro Gaetano , Salvatorelli Lucia , Castrogiovanni Paola 
Published: November 2023

Background and AimsVitamin D (VitD) is emerging for putative immunomodulatory and antifibrotic effect, and its deficiency is associated with NAFLD and sarcopenia. Olive oil is deemed as a factor of the effect of the Mediterranean diet nutritional profile. We investigated the role of VitD supplementation or deprivation in sedentary rats fed standard diet, high fat diet with animal fat or extra‐virgin olive oil (EVOO), studying the development of fatty liver disease and muscle tissue change.MethodsIn this study 28 male rats, 7–9 weeks of age, 200 g of body weight, on a 12‐hour light/dark cycle and ad libitum access to assigned diet and water, were randomly divided in 7 groups and fed for 10 weeks with 7 different dietary profiles [Regular diet (1); Regular diet + VitD (2), Regular diet VitD deprived (3); High fat/butter + VitD (4) and VitD deprived (5); High fat/EVOO plus VItD (6) and VitD deprived (7)]. Microscopic evaluation and histochemical study of liver and muscle was performed. The NAFLD Activity Score (NAS), ranging from 0 to 8, i.e. for steatosis (0–3), lobular inflammation (0–3), and ballooning (0–2), and the automated muscle fibers image analysis were used.ResultsNo difference was found among the 7 groups for final body weight gain, although rats fed a standard diet VitD deprived (3) had the final lower weight; the high fat/EVOO plus VitD rats (5) were heavier vs. controls (p 0,07). Rats on high fat/butter diet, both VitD enriched (4) or deprived (5), and high fat/EVOO VitD deprived (7) developed at last significantly greater NAS. Differently, rats on regular diet (1), notwithstanding with the adjunct (2) or deprivation of VitD (3), and rats fed with high fat/EVOO VitD enriched diet (6) did not show evidence of NAS increase. This last group (high fat/EVOO plus VitD) showed slight lobular inflammation without signs of steatosis, and their muscle fibers were hypertrophic respect to control and to other groups. In contrast, in group 5 (high fat/butter VitD deprived) the fibers were hypotrophic.ConclusionsVitD seems to be protective against steatosis in rats fed with EVOO‐based high fat diet, but not with butter‐based high fat diet. Moreover, VitD deficiency is associated with muscle fibers hypotrophy, effect counteracted by olive oil‐based diet. Extra‐virgin olive oil and Vitamin D may share a protective role on liver and muscle in sedentary rats against the induction of fatty liver and sarcopenia.
Identification of CtBP Targets in Breast Tumor Sections by Proximity Ligation Assay
Authors: Park Samson , Jones Alana , Yi Dae Ik , Liang Genqing , Kabbout Mohamed , Flanders Kathy , Wakefield Lalage M. , Byun Jung S. 
Published: November 2023

CtBP (Carboxyl‐terminal binding protein) is a dimeric nuclear protein and an epigenetic regulator that is activated in the presence of NADH to recruit and target a variety of histone modifying complexes and transcriptional regulators to chromatin, thus providing a defined mechanism through which carbohydrate metabolism can drive epigenetic regulatory events. We have recently shown that CtBP drives epithelial‐mesenchymal transition (EMT), genome instability, and acquisition of tumor‐initiating stem cell‐like pathways in breast cancer. Recently, we observed that elevated CtBP protein expression is correlated with poor survival of breast cancer patients in two independent cohorts. This finding led us to study further what complexes are associated with CtBP in breast cancer patient samples and whether such complexes could be linked to pathways that influence clinical outcomes. Immunoprecipitation assay of CtBP followed by mass spectrometry revealed CtBP's interactions with BRG1 (SMARCA4) and ZNF217 in the MCF‐7 breast cancer cell line. ZNF217 is a Zinc Finger DNA binding Transcription factor located on chromosome 20q13. ZNF217, amplified in 8–30% of breast cancers, is capable of transforming primary mammary epithelial cells, has been seen in hyperplastic mammary lesions, and plays a major role in TGF‐beta signaling pathways. BRG1 is a subunit of the SWI/SNF chromatin remodeling complex. The SWI/SNF is an ATP‐dependent chromatin remodeling complex that plays a role in a variety of cancers. Most notably, its subunits are mutated in 20% of cancers, with lesions that either disrupt tumor suppressor activity or confer oncogenic properties on the SWI/SNF complex.To assess whether these complexes form in patient tumor samples, we employed the Proximity Ligation Assay (PLA) technology. PLA enables detection of protein:protein interactions with sensitivity at the level of single molecule resolution in tissue. We performed PLA on formalin fixed and paraffin embedded (FFPE) tumor samples from breast cancer patients and could demonstrate significant levels of CtBP1:BRG1, CtBP2:BRG1 and ZNF217:CtBP1 interactions. Recent studies from our lab and those of others suggest a cooperative interaction between CtBP and BRG1 in the induction of drug resistance genes. To assess functional relationship between CtBP and BRG1 in patient samples, we measured the transcript abundance of the multiple drug resistance gene MDR1 (ABCB1) in patient samples stratified by BRG1 and CtBP expression. The findings show a significant correlation between MDR1 transcript abundance in patients with both high levels of BRG1 and CtBP (P‐value = 0.021). This data suggest future applications of BRG1/CtBP PLA as a possible screen for the activation of drug resistance pathways in breast cancer patients. Finally, we provide evidence that adopting this assay to tissue microarray (TMA) format is highly feasible.
Implication of Aberrant Protein Expression in the Etiology of Pancreatic Cancer
Authors: Nyaga Simon G , Akobundu Blessing , Giwa‐Otusajo Jamiu , Hazel Kaisha 
Published: November 2023

Pancreatic cancer is a leading cause of cancer mortality in the U.S. American Cancer Society estimates that there will be 53,670 new cases and 43,090 pancreatic cancer death in 2017 in the U.S. Although many risk factors are known, the precise mechanisms involved in the development/progression of the malignant phenotype of this devastating disease are poorly understood. The interaction of the risk factors with cellular DNA may result in abnormal protein changes that could affect the functions of essential biological pathways in cells. The goal of this study is to understand the molecular mechanisms involved in the etiology of pancreatic cancer. To address our goal, we focused on identification of differentially expressed proteins in a pancreatic cancer cell line, BxPC‐3, relative to a nonmalignant pancreatic cell line, HPDE‐6. The cell lines were cultured and cell‐free extracts prepared followed by protein separation by SDS polyacrylamide gel electrophoresis (SDS‐PAGE) and staining using Coomassie blue. Specific candidate proteins were identified by liquid chromatography in tandem with mass spectrometry (LC‐MS/MS). Several proteins were shown to be differentially expressed including; MYH10, CEACAM6, and IGFBP‐5 which were confirmed to be highly over‐expressed (approximately 5×, 10× and 5× respectively) in BxPC‐3 cell line compared to HPDE‐6 cell line using Western Blot analysis. Interestingly, these proteins are associated with biological processes such as cell proliferation, differentiation, apoptosis, cell adhesion, and metastasis: processes commonly altered in many cancers. This aberrant protein expression could be associated with abnormal protein functions and interactions that may be critical in the initiation/progression of pancreatic cancer. Hence, these findings implicate IGFBP‐5, CEACAM6, and MYH10 in the etiology of pancreatic cancer. Further biochemical characterization may yield biomarkers useful in effective therapeutic intervention of pancreatic cancer.Support or Funding InformationDepartment of Biology, Morgan State University