bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterizing the transcriptional regulation of importin α1 expression in non‐small cell lung cancer
Authors: Yu Chia‐Jung , Cheng Ya‐Yun , Feng Hsiang‐Pu , Li Po‐Yu , Wang Chih‐Liang 
Published: November 2023

KPNA2 (importin α1), an importin α family member is overexpressed and associated with cancer invasiveness in several types of human cancer. However, the upstream signaling as well as the transcription factor responsible for the regulation of KPNA2 expression remains unclear. Previously, we identified KPNA2 as a potential biomarker for non‐small cell lung cancer (NSCLC) and that mTOR signaling positively regulated Dp1/E2F1‐mediated transcription of KPNA2. We also found that KPNA2 might be involved in response to DNA damage stimulation, DNA metabolic processes, DNA repair and cell cycle. We herein show that interferon regulatory factor 1 (IRF1), a transcription factor with antitumor activity would suppress the expression of KPNA2 in NSCLC. The binding site of IRF1 in Kpna2 promoter was examined by chromatin immunoprecipitation assay. The ATM serine/threonine kinase inhibitor treatment dramatically induced the expression of IRF1, whereas significantly down‐regulated the expression of KPNA2 in NSCLC cells. Importantly, IRF1 knockdown restored the reducing level of KPNA2 in ATM inhibitor‐treated cells, supporting the suppressive role of IRF1 in regulation of KPNA2 expression. We also found that inhibiting either mTOR or ATM pathway significantly reduced the E2F1 expression but induced the IRF1 expression in vivo. Our result collectively show for the first time that IRF1 suppressed the KPNA2 expression and that two pathways, mTOR and ATM signaling might be involved in this IRF1‐mediated transcriptional regulation of KPNA2 expression in NSCLC.Support or Funding InformationMinistry of Science and Technology, Taiwan, R.O.C. (105‐2320‐B‐182‐035‐MY3) and Chang Gung Medical Research Fund (BMRP894).
Characterization of a patient fibroblast cell line with Infantile Neuronal Ceroid Lipofuscinosis disorder
Authors: Balouch Bailey , Chu‐LaGraff Quynh 
Published: November 2023

Infantile Neuronal Ceroid Lipofuscinosis (INCL) belongs to a family of pediatric neurodegenerative disorders collectively known as Batten Disease. INCL is caused by mutations in the palmitoyl protein thioesterase 1 (PPT1) gene, leading to retinal and CNS deterioration due to accumulation of autofluorescent storage materials in the lysosome. Although advances have been made in modeling the disease in various organisms, the elucidation of defined mechanistic pathways responsible for disease pathology and effective treatment remains a challenge. The goal of the present study is to characterize the cellular behavior of a human patient fibroblast cell line deficient in the PPT1 enzyme. PPT1 deficient cells were derived from a donor with Tyr247His and Met1Ile compound heterozygous mutations. The donor cells are characterized and compared to the two PPT1 expressing fibroblast cell lines, HFF and MRC‐5, using assays of cell morphology, cell viability, and autofluorescent accumulations. Future work aims to establish an Induced Pluripotent Stem Cell (iPSC) line using the Yamanaka technique, in order to continue studying the pathology of the disease. Specifically, neural progenitor cells deriving from these iPSC cells will be characterized and compared to wild type iPSCs to assess cell morphology, cell viability, autofluorescent accumulations, and neuronal function and pathology.Support or Funding InformationUnion College Student Research Grant
Modulation of Inflammasome Signaling by Advanced Glycation End Products (AGEs)
Authors: Son SeungHwan , Hwang Inhwa , Yu Je‐Wook 
Published: November 2023

Deregulated immune response in obese condition leads to not only chronic inflammation but impaired protection against microbial infection such as influenza virus. The underlying mechanism by which obesity is related to the impaired host immune defense against pathogen invasion is poorly described. Here, we found that advanced glycation end products (AGEs), which are elevated in obese condition, specifically inhibit the activation of NLRP3 inflammasome in bone marrow‐derived macrophages (BMDMs). Pretreatment of AGEs attenuated diverse NLRP3 stimuli‐triggered caspase‐1 activation and interleukin‐1 beta (IL‐1β) secretion, but failed to affect AIM2‐ and NLRC4‐mediated inflammasome activation. AGEs also decreased ASC oligomerization and mitochondrial reactive oxygen species (ROS) production in response to NLRP3 inflammasome stimulator. However, treatment of receptor for AGEs (RAGE) antagonist FPS‐ZM1, did not alter the NLRP3 inflammasome‐suppressing effect of AGEs. Furthermore, AGEs abolished inflammasome activation triggered by poly I:C transfection or influenza virus infection. Taken together, our results suggest that AGEs potentially contributes to impaired innate immune response in obese condition by suppressing NLRP3 inflammasome signaling.Support or Funding InformationThis work was supported by the Bio & Medical Technology Development Program of the NRF funded by the Korean Government (2015M3A9B6073856)
Detection and Quantification of Probiotic Strains in Clinical Fecal Samples of Healthy Adults by Real‐time PCR
Authors: Nagulesapillai Varuni , Belvis Jocelyn , Tompkins Thomas , Girard Stephanie‐Anne 
Published: November 2023

INTRODUCTIONA randomized, double‐blind, placebo‐controlled, crossover clinical study (NCT01879098) on healthy, middle‐aged adults investigated the effects of three probiotic strains, Bifidobacterium animalis subsp. lactis B94, Lactobacillus plantarum HA119, and Bacillus subtilis R0179 on bile acid metabolism, satiety, and inflammation. In order to substantiate positive outcomes, probiotic strains must persist during transit through the gastrointestinal tract of participants. The objective of this sub‐study was to detect and quantify HA119 and R0179 at the strain level in fecal samples using previously designed primers for real‐time PCR (qPCR).METHODOLOGYParticipants of the clinical study were randomized to receive one capsule per day of a probiotic strain or placebo for six weeks. Following a four week washout period, participants were crossed to the other treatment (probiotic to placebo or placebo to probiotic). Fecal samples were collected at the baseline and final time points of each intervention for a total of four stool samples per participant. DNA isolated from fecal samples of participants in the L. plantarum HA119 (n = 136) and B. subtilis R0179 (n = 124) groups were analyzed by a SYBR‐green based qPCR method for HA119 and R0179, respectively. Strain‐specific primer targets included a gene encoding a phage protein for HA119, and a hypothetical protein for R0179. All fecal samples from participants in the B. lactis B94 group were not analyzed for B94 due to the lack of strain‐specific primers.RESULTSThe HA119 strain was detected in 97% of the participants in the HA119 arm. The mean HA119 level in the feces from the final time point of probiotic intervention was 7.34 ± 0.86 log bacteria/g of feces. R0179 was detected in 97% of the participants in the R0179 group at mean 6.52 ± 0.38 log bacteria/g of feces in the final time point of probiotic intervention. The absence of the probiotic strains in the feces following the four week washout period suggests that the duration of the washout period was adequate between the intervention periods.CONCLUSIONSOverall, these results demonstrate the use of strain‐specific primers for the detection and quantification of probiotic strains HA119 and R0179 in complex fecal matrices containing numerous gut microbes. The ability to show persistence of specific probiotic strains in feces could help monitor participant compliance in clinical trials. This qPCR study also suggests that a four week washout period between intervention periods is sufficient for crossover clinical studies with probiotic intervention.Support or Funding InformationLallemand Health Solutions
Generation of Leigh Syndrome Cell Models
Authors: Alvarado Joshua 
Published: November 2023

Leigh Syndrome (LS) is a neurological disease that stems from mutations in the subunits of mitochondrial respiratory chain subunits. These mutations decrease electron transport chain (ETC) efficiency, leading to decreased cellular ATP levels and increased reactive oxygen species (ROS) levels. There is currently no therapeutic approach to combat this degenerative disorder, and patients typically die by 8–10 years of age. There are also very few models with which to study this disease. We have generated LS cell models using both a chemical and genetic approach. Chemically, we inhibit ETC activity with low levels of rotenone, an ETC poison, in order to suppress ETC‐dependent ATP generation to levels seen in LS patients. Genetically, we use siRNA to knock down the ETC subunits that are mutationally inactivated in LS patients, also disrupting ETC function. Through these approaches, we have constructed LS cell models that can now be used to investigate potential therapeutics.Support or Funding InformationCSUPERB New Investigative Grant
The optical spectroscopic properties of glycation induced changes in hemoglobins
Authors: Sriramoju Vidyasagar , Dudley Raymond , Secor Jeffrey A , Ashrafi Solyman , Alfano Robert R 
Published: November 2023

The glycation induced changes in human hemoglobin is studied using absorption, fluorescence, Raman and time resolved fluorescence spectroscopic methods. The non‐enzymatic glycosylation of hemoglobin as a result of sustained elevated blood sugar levels changes the chemistry of its native chromophore and fluorophore moieties as a result it's tertiary structure gets altered significantly. These post translational molecular modifications would induce changes in optical properties like absorption, fluorescence emissions, fluorescence lifetimes and Raman finger prints. In this study the optical properties of normal hemoglobin are compared with glycated hemoglobin under non‐denaturing conditions in order to evaluate their potential as diagnostic and/or investigative biomarkers for chronic hyperglycemic conditions such as Diabetes mellitus Type 1 and 2.Support or Funding InformationNxGen Partners, Ross Tower, 500 N. Akard Street, Suite 1820 Dallas TX 75201
Identification of Metabolites of Maresin 1 in Human Neutrophils
Authors: Gijón Miguel A , Almstrand Ann‐Charlotte , Johnson Chris A , Murphy Robert C , Zarini Simona 
Published: November 2023

The resolution of inflammation, once considered to be rather passive, is now understood to be a complex, regulated process. One of the components in this process is the action of pro‐resolving lipid mediators, including lipoxins, resolvins, protectins and maresins. Maresin 1 (MaR1), derived from the oxidation of docosahexaenoic acid (22:6, n‐3), exhibits biological activities relevant to the resolution of inflammation, such as inhibiting accumulation of neutrophils and enhancing efferocytosis by macrophages.Measurements of lipid mediators derived from arachidonic acid (20:4, n‐6) or docosahexaenoic acid have been quite successful in tissue exudates or cell culture‐based systems. However, efforts to measure these lipids in blood as a correlate to their production in vivo during an inflammatory episode have not been as straightforward and are somewhat controversial. In fact, much of our understanding of the role of prostaglandins and leukotrienes produced in vivo has come from measurement of urinary metabolites rather than plasma measurements.This work is aimed at identifying metabolites of MaR1 and their accumulation in urine, which will then allow us to develop sensitive and specific mass spectrometry‐based assays for their quantitation. As a first approach, we have investigated the metabolism of MaR1 by human neutrophils, which are key cells recruited to inflammatory sites where MaR1 is known to be produced in the first place. Using a combination of liquid chromatography, gas chromatography, UV spectrometry and mass spectrometry, we have identified five novel metabolites of maresin 1, which are produced in a time‐ and dose‐dependent manner by human neutrophils We present here the chromatographic and spectral properties of these metabolites, as well as their proposed chemical structures. Four of these metabolites are oxidized forms of MaR1, and contain one or two hydroxyl groups. Preliminary evidence suggests that at least one of these metabolites may also be present in the urine of mice injected with MaR1.These results open the possibility of investigating the role of MaR1 in experimental animal models and in human disease by analyzing its urinary metabolites. This will provide insight into the progression and possible treatment of several human diseases that include inflammation as a component in their progression.Support or Funding InformationThis work is supported in part by a grant from the Cayman Biomedical Research Institute.
Skin of the Catfish (Arius Bilineatus, Val.) Contains Lipid Compounds that Regulate NET Formation and NET‐Mediated Inflammation
Authors: Pace‐Asciak Cecil , Al‐Hassan Jassim M. , Afzal Mohammad , Paul Bincy , Oommen Sosamma , Khan Meraj , Liu Yuan Fang , Palaniyar Nades 
Published: November 2023

Neutrophil Extracellular Traps (NETs) are networks of DNA fibers that are coated with cytotoxic components, released by neutrophils. NETs are beneficial for killing microbial pathogens, extracellularly, or by ensnaring toxins and cytokines. In different disease context, NETs can either be pro‐inflammatory or anti‐inflammatory. Therefore, identifying compounds that could regulate NET formation is important. Two major pathways of NETosis have been identified: NADPH oxidase‐dependent and calcium‐mediated NADPH oxidase‐independent NETosis. We have recently shown that NETosis is stimulated by a natural lipid eicosanoid, hepoxilin A3, which has pro‐inflammatory properties. Depending on the concentration, hepoxilin A3 induces either one or both types of NETosis. Preparations from the skin of the catfish contain lipids and proteins which have several important biological properties, such as anti‐thrombotic, anti‐inflammatory and wound healing activities. Our goal is to isolate and characterize products present in the lipid fractions of the preparations and study their biological activities. The lipids were separated from the proteins and fractionated by column chromatography. The neutral lipid fraction was separated into several sub‐fractions by thin layer chromatography (TLC). These sub‐fractions were tested in a battery of bioassays including the NETosis assays. We discovered that various isolated TLC fractions regulated NETosis, and importantly suppressed NETosis induced by the calcium ionophore A23187 to various degrees. This discovery suggests a novel mechanism for the anti‐inflammatory actions of the preparations.Support or Funding InformationThe study was Supported by: A grant from the Kuwait Foundation For Advancement of Sciences (KFAS 2013‐120701 A‐C), Kuwait University (KU SL03/14) and the Hospital for Sick Children and University of Toronto.
Effect of 8‐Hour Time Restricted Feeding on Body Weight in Obese Subjects
Authors: Gabel Kelsey , Hoddy Kristin K , Haggerty Nicole , Varady Krista A 
Published: November 2023

BackgroundIt has been speculated that time restricted feeding (TRF) could offer a non‐pharmacological intervention for weight loss in obese patients. No studies to date have examined the effect of TRF on body weight and coronary heart disease (CHD) risk factors in obese adults.ObjectiveAccordingly, this study assessed the effects of 12 weeks of 8‐hour time restricted feeding (10am–6pm) on body weight and CHD risk factors.MethodsIn this pilot study, obese subjects (n = 9) were instructed to eat only between the hours of 10am–6pm daily for 12 weeks.ResultsBody weight decreased (P = 0.003) by −4.9% ± 1.9 (4.9 ± 1.9 kg) from baseline. Heart rate decreased (P = 0.037) by 4.7 ± 5.6 bpm from baseline. Fat mass decreased from baseline (P = 0.003) by −3.7% ± 3.1. Blood pressure, plasma lipids, and fat free mass remained unchanged.ConclusionThese findings suggest that consuming food within an 8‐hour window can facilitate weight loss. The effect of TRF on CHD risk warrants further investigation.Support or Funding InformationCampus Research Board Grant at University of Illinois at Chicago
Genetic and Epigenetic Signature Identifies Individuals with Elevated Response to Vitamin B12 Supplementation
Authors: Johnson Jessie Nicodemus , Brown Mark 
Published: November 2023

Vitamin B12 is essential for many aspects of human health. Deficiencies are largely caused by inadequate intake or reduced absorption, and are associated with increased incidence of neurological, cognitive and cardiovascular decline. Using a previously published dataset of B12/ folic acid supplementation in elderly individuals (GSE74548), we investigated the effect of a variant in the methylenetetrahydrofolate reductase gene (MTHFR; rs1801133) on serum B12 and folate levels at baseline and after 2 years of supplementation. As well as, the association between baseline genome‐wide DNA methylation (Infinium 450K DNA methylation chip) in peripheral blood mononuclear cells (PBMCs) and supplementation induced changes in circulating B vitamin levels. After supplementation, we observed that those with the rs1801133 CC genotype had elevated circulating B12 but not folic acid levels, relative to the rs1801133 TT genotype (P = 0.0073 and P = 0.47, respectively). Moreover, individuals with the CC genotype clustered into two distinct B12 response groups (P = 2.8 × 10−6), termed high and low responders. Additionally, we observed an enrichment of low p‐values among baseline DNA methylation patterns and change in circulating B12 levels after supplementation in CC individuals only (empirical P < 1 × 10−5). These sites are not near genetic variants or genes known to influence vitamin B12 uptake. Overall, we present evidence that epigenetic signatures at baseline may predict an individual's response to B12 supplementation and may highlight novel pathways of regulation. Elucidation and further understanding of pathways associated with elevated response to B12 supplementation, may aid in the treatment of chronically deficient individuals.Support or Funding InformationUSANA Health Sciences
Effects of an Egg‐based, Carbohydrate‐restricted Diet on Body Composition, Fat Distribution, and Metabolic Health in Older Adults with Obesity: Preliminary results from a randomized controlled trial.
Authors: Goss Amy Miskimon , Gower Barbara A , Soleymani Taraneh , Stewart Mariah , Fontaine Kevin 
Published: November 2023

BackgroundAge‐related loss of lean mass, accumulation of visceral adipose tissue (VAT), and insulin resistance place aging adults with obesity at particularly high risk of cardio‐metabolic disease. By reducing insulin demand, carbohydrate (CHO)‐restricted diet patterns that include foods such as whole eggs may promote loss of body fat, specifically from the visceral cavity, without compromising lean mass and improve metabolic health in aging adults with obesity.ObjectiveThe objective of this study was to determine if consumption of an egg‐based lower‐CHO/high‐fat diet (EBD) vs a standard CHO‐based/low‐fat diet (STD) results in loss of total and visceral fat, preservation of lean mass, and improvements insulin resistance and the lipid profile.DesignIn a randomized clinical trial, 26 men and women age 60–75yrs. with obesity (BMI 30–40kg/m2) consumed either an EBD (<25:25:>50% energy from CHO:protein:fat) or STD (55:25:20) for 8 weeks. Participants were not asked to restrict total energy intake. The EBD group was provided eggs throughout the study, whereas the STD group was provided breakfast bars to consume. Body composition by DXA, resting energy expenditure (REE) by indirect calorimetry, and insulin, glucose, HOMA‐IR and lipids by fasting blood draw were assessed at baseline and after the 8‐week intervention.ResultsParticipants lost 11.0% and 2.3% total fat following the EBD and STD diet, resp. (p<0.01 for difference between diets). The EBD group experienced ~3‐fold greater loss in VAT compared to the STD group (−23.3% vs −7.1%, p<0.01 for difference between diets) and greater decrease in HOMA‐IR (p<0.01), whereas there were no significant between‐group differences in change of total lean mass or REE. Among those in the EBD group, there was a significant decrease in triglycerides and increase in HDL.ConclusionsWhen compared to a standard high‐CHO, low fat diet, consumption of a diet lower in CHO supplemented with 3 whole eggs per day resulted in loss of fat mass, specifically from the visceral cavity while preserving lean mass and resting metabolic rate. This diet pattern also resulted in significant improvements in indices of metabolic health including insulin resistance, triglycerides and HDL cholesterol.Support or Funding InformationEgg Nutrition Center
Desensitization of Basal Cell Carcinoma to The Anti‐Tumoral Effect of Vitamin D: Role of REDD1
Authors: Khasawneh Rawia , Unnikrishnan Archana , Mahmoud Bassel , Hamzavi Iltefat , Heydari Ahmad R 
Published: November 2023

The relationship between vitamin D and non‐melanoma skin cancer is not clear. Epidemiological studies are inconsistent and inconclusive, and mechanistic studies are lacking. Vitamin D is a seco‐steroid hormone, whose nuclear receptor, vitamin D receptor (VDR), is a nuclear transcription factor. It has been suggested that vitamin D possesses anti‐proliferative and pro‐differentiation effects by negatively regulating important signaling pathways. In particular, the VDR target gene ‐ regulated in development and DNA damage response 1 (REDD1) ‐ inhibits the mechanistic target of rapamycin (mTOR) pathway, thus impacting cellular growth. In response to DNA damage, REDD1 transcription is up‐regulated by elevated levels of tumor protein 53 (p53), resulting in inhibition of mTOR pathway. Subsequently, reduction of p53 results in feedback inhibition at the translation level.This case‐control study aimed to explore the impact of vitamin D status on the onset and progression and possibly treatment of basal cell carcinoma (BCC). Three tissue samples were collected from 20 BCC patients (Cancer, Proximal, and Distal), and 6 cancer‐free individuals from southeast Michigan. BCC and its feeding cells seemed to up‐regulate vitamin D activation enzymes, VDR, and its co‐activators, thus proposing higher local activity of vitamin D. Despite the significantly increased protein levels of REDD1 in the cancer tissue, our data showed that VRD's ability to down‐regulate mTOR pathway through REDD1 was diminished. Interestingly, Vitamin D negative regulation of Hedgehog‐Gli pathways was also lost in the cancer tissue. A gain of function mutation in the Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS), upstream of mTOR pathway, was detected in all BCC specimens. In conclusion, we propose that the anticipated role of vitamin D is not conserved in BCC tissue, possibly related to additional mutations.