bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lactose Intolerance, calcium, vitamin D and parathyroid hormone levels in type 2 diabetic patients
Authors: Rana SatyaVati , Malik Aastha , Bhadada Sanjay K , Sachdeva Naresh , Morya Rajesh Kumar , Sharma Gaurav 
Published: November 2023

BackgroundType 2 diabetes mellitus is a chronic metabolic disorder. Common gastrointestinal symptoms in type 2 diabetic patients are nausea, vomiting, flatulence, constipation and/ or diarrhea. Reason for these symptoms may be lactose intolerance. Vitamin D, calcium and parathyroid hormone further regulate the bone mineralization in our body.AimThe present study was planned to measure lactose intolerance, levels of vitamin D, calcium, and parathyroid hormone in type 2 diabetic patients.Material and Methods150 patients and 150 age and sex matched healthy controls attending Endocrinology Clinic in PGI, Chandigarh were enrolled. Lactose intolerance was measured using non‐invasive lactose breath test. 25‐hydroxyvitamin D3 and Parathyroid hormone were measured in plasma using immunoassay. Plasma calcium was measured using auto analyzer. T score was recorded from DXA scan for bone mineral density measurement.ResultsLactose intolerance was observed in 89/150 (59.3%) diabetic patients and 63/150 (42%) in controls. Levels of vitamin D3, calcium and parathyroid hormone were significantly less in diabetic patients as compared to controls. Furthermore, levels of plasma vitamin D3, calcium and parathyroid hormone were more decreased in lactose intolerant diabetic patients than lactose tolerant patients. 67% of diabetic patients suffered from osteoporosis and 20% of controls. 80% diabetic patients and 16% controls with osteoporosis suffered from lactose intolerance.ConclusionFrom this study we can conclude that measurement of lactose intolerance using non‐invasive lactose breath test is suggested for type 2 diabetic patients so that deficiency of vitamin D and calcium can be taken care off.Support or Funding InformationIndian Council of Medical Research, New Delhi, India
Lipids and Cholesterol‐Lowering Activity of Red Cabbage Microgreens
Authors: Jiang Xiaojing , Huang Haiqiu , Xiao Zhenlei , Yu Lu , Pham Quynhchi , Yu Liangli (Lucy) , Luo Yaguang (Sunny) , Wang Thomas T.Y. 
Published: November 2023

Cardiovascular disease (CVD) is the leading cause of death in the United States and diet‐induced hypercholesterolemia is a major risk factor. Population, as well as experimental evidence, support that the consumption of a variety of vegetables can lower the risk of CVD through modulation of hypercholesterolemia. Microgreens are tiny edible greensharvested from vegetables and herbs at 7–14 days after germination, and are reported to possess a higher density of nutrients when compared to their mature counterparts. However, little is known about the health promoting efficacies of microgreens in terms of their effect on lipid and cholesterol levels. The present study used a rodent diet‐induced obesity model to address this question. C57B/6NCr mice (n=62, male, five week) were randomly assigned to six groups: 1) low fat diet (with 10% calories from fat); 2) high fat diet (with 45% calories from fat); 3) low fat diet+1.95%red cabbage microgreens; 4) low fat diet+1.95% mature red cabbage; 5) high fat diet+1.95% red cabbage microgreens; 6)high fat diet+1.95% mature red cabbage. The animals were on their respective diets for eight weeks. We found supplementing microgreens attenuated high fat diet induced weight gain after 8 weeks (17%). Moreover, we found microgreens significantly lowered circulating LDL levels (34%), hepatic triglycerides (23%)and cholesterol ester (65.5%) levels in animals fed a high fat diet. The effects of microgreens on hepatic triglycerides and cholesterol ester appeared to coincide with inhibition in triglycerides synthesis enzymes diacylglycerol O‐acyltransferase 1 (DGAT1), glycerol‐3‐phosphate acyltransferase (GPAM), cholesterolester synthesis enzymes acetyl‐CoA acetyltransferase 3 (ACAT3) and lecithin‐cholesterol acyltransferase (LCAT). However, no changes in expression in the genes related to cholesterol metabolism including sterol regulatory element binding transcription factor 2 (SREBP2), 3‐hydroxy‐3‐methylglutaryl‐CoA reductase (HMGCR), acyl‐CoA oxidase (ACOX), cytochrome P450, family 7, subfamily A, polypeptide 1 (CYP7A1) were observed. In summary, our data support dietary consumption of red cabbage microgreens modulates cholesterol metabolism, weight gain, and may protect against hypercholesterolemia and CVD.Support or Funding InformationThomas T. Y. Wang Address:Room 132, 10300Baltimore Ave, Bldg. 307‐C, BARC‐EAST, Beltsville, MD, 20705Phone number: 301‐504‐8459 Fax:301‐504‐9062Email address: tom.wang@ars.usda.gov
Consistent Weight Gain Tracking is Associated with a Reduction in Gestational Weight Gain in High Income Women
Authors: Olson Christine M. , Graham Meredith L. , Strawderman Myla S. 
Published: November 2023

ObjectiveTo determine the importance of using the weight gain tracker in a multi‐feature integrated mobile phone and online healthy lifestyle intervention designed to prevent excessive gestational weight gain (GWG).MethodsA 3‐arm randomized controlled trial with pregnant women in two early pregnancy body mass index (BMI) groups: normal and overweight plus obese class 1; and two income groups: low (Medicaid‐eligible) and high household incomes was conducted to evaluate the effectiveness of the integrated mobile phone and online intervention. Two arms received intervention during pregnancy. Data were collected through online surveys, a medical record audit, and weight tracking was automatically logged by the project website. Data were analysed using both modified Poisson and linear regression models controlling for sociodemographic and timing of weight measurement covariates. Three gestational weight gain outcomes were examined: prevalence of excessive total GWG; prevalence of excessive weekly GWG from 20 weeks gestation until delivery; and total GWG in kg. Consistent weight gain tracking was defined as at least one weight entry in each 45 day time interval of enrolment in the study.ResultsA racially and ethnically diverse sample of 1,335 18 to 35 year‐old healthy pregnant women was recruited into the trial through community‐based practices and clinics and online enrolment. Among higher income women, 49% of women with normal BMI and 27% of overweight plus obese BMI women were consistent weight gain trackers. Tracking was less common among lower income women: 13% among normal BMI and 11% among overweight plus obese BMI. Among higher income normal BMI women, consistent weight gain tracking was significantly associated with all three outcomes: reduced risk of excessive total GWG (p = 0.03); reduced risk of excessive weekly rate of GWG (p = 0.0009); and 1.73 kg less total GWG (p = 0.0002). Among overweight plus obese higher income women, consistent tracking was associated with near significant reductions in the two measures of excessive GWG (p = 0.07 and 0.09) and a significant reduction of 3 kg in total GWG (p <0.0001). Consistent weight gain tracking was not associated with any of the GWG outcomes in low income women.ConclusionsAmong pregnant women with household incomes above the Medicaid eligibility cut‐off, consistent weight gain tracking is an important feature of online and mobile interventions for reducing excessive GWG.Support or Funding InformationGrant No. HL096760
The Role of p120‐catenin and PIK3CA in Migration in Head and Neck Squamous Cell Carcinoma
Authors: Kidacki Michal , Lehman Heather L , Welsh Patricia A , Warrick Joshua I , Stairs Douglas B 
Published: November 2023

Over half a million people worldwide are diagnosed with head and neck squamous cell carcinoma (HNSCC). A third of the newly diagnosed patients won't survive the next five years. Additionally, approximately 15% of these patients already have distant metastases at the time of diagnosis. Therefore it is of profound interest to understand the mechanism driving HNSCC metastasis.p120‐catenin (p120ctn) is a tumor suppressor that is lost in 19% of HNSCC. PIK3CA, a gene coding for the catalytic subunit of PI3‐kinase, is mutated in 21% (E545K and H1047R being the most common mutations) and overexpressed in an additional 20% of HNSCC. Both, p120ctn loss and PIK3CA mutations individually have been shown to play a role in metastasis in a number of epithelial cancer models. Considering the frequency at which both p120ctn and PIK3CA are dysregulated in HNSCC, it is very likely that these two changes may be found in the same patients, increasing a cancer's aggressiveness. Therefore, we hypothesize that cells harboring both p120ctn down‐regulation and PIK3CA mutations may represent a more malignant cell population than the cells with either of these changes alone.The tumorigenic effects of p120ctn down‐regulation and PIK3CA mutations were tested using normal oral keratinocytes (NOK). NOK cell lines were generated by down‐regulating p120ctn alone or in conjunction with an overexpression of either of the PIK3CA mutants, E545K or H1047R. Migratory and invasive capabilities of these cell lines were assessed. Boyden chamber migration assays showed that either p120ctn knockdown or each of the PIK3CA mutations alone increased cell migration 2.5 to 3‐fold compared to the control. However, when p120ctn knockdown was coupled with either the E545K or H1047R PIK3CA mutation, the cell migration increased 4‐fold. A similar increase was observed for the invasive capabilities of these cells.Signaling pathways were interrogated to identify the mechanism(s) responsible for the observed increase in cell migration. Both phospho‐STAT3 (Y705) and active, GTP‐bound RhoA were found to be increased in NOKs with p120ctn down‐regulation or PIK3CA mutations alone. Even greater increases were detected in cell lines containing both p120ctn down‐regulation and PIK3CA mutations. We are currently testing whether these increases in phospho‐STAT3 or active RhoA are responsible for the observed increase in cell migration and whether crosstalk between these signaling pathways exists. In conclusion, both p120ctn down‐regulation and PIK3CA mutations act cooperatively to increase migration/invasion, possibly via the STAT3 or RhoA pathway.
Nrf2 But Not Autophagy Activation Is Associated with Resistance to EGFR Inhibitor‐Induced Lung Tumor Cell Apoptosis
Authors: Li Yuan , Zhou Yan , Ni Hong‐Min , Zhong Hua , Ding Wen‐Xing 
Published: November 2023

ObjectiveTo understand the mechanism of the resistance of non‐small cell lung cancer (NSCLC) to epidermal growth factor receptor (EGFR) inhibitor treatment.BackgroundNSCLC is one of the most common malignancies in the world, of which a group of patients have activating EGFR mutations. Icotinib and Gefitinib are two tyrosine kinase inhibitors (TKIs) that bind to the tyrosine kinase domain in EGFR and inhibit EGFR activity, which have been used to treat NSCLC. However, natural and acquired resistance significantly limits the efficacy of EGFR‐TKIs, and the mechanism of the resistance is not fully understood. Autophagy is a highly conserved, genetically programmed degradation pathway that removes damaged organelles and protein aggregates in response to various stimuli to maintain cellular homeostasis. Autophagy inhibits tumorigenesis but promotes tumor progression at later stages. Nuclear factor (erythroid‐derived 2)‐like 2 (Nrf2) is a transcription factor and regulates the expression of antioxidant genes. Activation of Nrf2 is a protective mechanism for normal cells under oxidative stress, and also for cancer cells from chemotherapeutic agents that facilitates cancer progression. Whether autophagy and Nrf2 activation contribute to the sensitivity of NSCLC to TKI treatment has been incompletely understood.MethodsWe compared the sensitivity of A549, an EGFR wild type cell line derived from lung carcinoma, and HCC827, an EGFR mutant cell line derived from lung adenocarcinoma, to TKI treatment, and determined the role of autophagy and Nrf2 activation in TKI‐mediated cell death.ResultsIcotinib and Gefitinib induced significant apoptosis in HCC827 cells in a dose‐dependent manner, while they did not cause apoptosis in A549 cells. TKI inhibitors induced autophagy flux and mTOR inhibition in HCC827 but not in A549 cells. Intriguingly, suppression of autophagy by chloroquine, a lysosomal inhibitor, did not affect TKI‐induced cell death. A549 cells had lower basal level of autophagy but higher basal level of Nrf2 activation than HCC827 cells. Brusatol, a Nrf2 inhibitor, did not affect autophagy in A549 or HCC827 cells, but significantly decreased the cell viability in A549 and HCC827 cells. However, Brusatol did not further sensitize A549 or HCC827 cells to TKI‐induced cell death.ConclusionA549 cells are more resistant to TKI‐induced apoptosis than HCC827 due to persistent activation of Nrf2. Although autophagy activity is higher in HCC827 cells than A549 cells, it is not essential for the sensitivity of HCC827 or A549 cells for TKI. Inhibition of Nrf2 reduces the cell viability of TKI resistant A549 cells although it does not show synergistic effects with TKI.Support or Funding InformationNIH RO1 AA020518, NIH R01 DK 102142, P20 RR021940 (COBRE)
Neutrophil Extracellular Traps Drive Bleomycin‐Induced Lung Fibrosis by Regulating TGFβ1‐Dependent Interactions of Platelets and Macrophages
Authors: Riehl Dennis R. , Roewe Julian , Klebow Sabrina , Esmon Naomi L. , Eming Sabine , Colucci Giuseppe , Schäfer Katrin , Gunzer Matthias , Waisman Ari , Ward Peter A. , Esmon Charles T. , Bosmann Markus 
Published: November 2023

Neutrophil extracellular traps (NETs) are extracellular histones and DNA expelled from polymorphonuclear neutrophils (PMNs). NETs are released during inflammation as an innate immune defense mechanism. NETs not only exert bactericidal activities but are toxic for host cells and thus promote tissue injury. In the past, many reports have defined the important roles of NETs during acute infections and acute inflammatory diseases. On the other hand, our current knowledge on the contribution of NETs during chronic inflammation, adaptive immunity and fibrotic diseases leaves much to be desired.In this report, we uncover the immunologic networks initiated by NETs during the natural course of bleomycin‐induced lung fibrosis in mice. First, we designed a model of inducible transient genetic depletion of Ly6G+ PMNs by injection of diphtheria toxin in Ly6G‐Cre × iDTR mice. Depletion of Ly6G+ PMNs simultaneously with intra‐tracheal administration of bleomycin was sufficient to decrease the build‐up of extracellular matrix, T cells and cytokines (e.g. TGFβ1) in lungs after 4 weeks. Bleomycin mediated the release of citrullinated extracellular histones in broncho‐alveolar lavage fluids in dependency of PMNs with a surge after 2 days. Neutralization of extracellular histones by monoclonal anti‐histone H4 antibodies significantly reduced the expression and accumulation of extracellular matrix proteins and TGFβ1 during lung fibrosis. Platelets represented a major source (≥70%) of plasma TGFβ1 and purified extracellular histones activated platelets to release TGFβ1. Accordingly, bleomycin‐induced lung fibrosis was ameliorated in mice with platelet‐specific genetic deletion of TGFβ1 (PF4‐Cre × TGFb1flox/flox mice). TGFβ1 signaling required TGFβ receptor II and multiple down‐stream signaling pathways in macrophages. Mice with specific genetic ablation of the TGFβ receptor II in LysM+ macrophages (LysM‐Cre × TbRIIflox/flox mice) were also protected in bleomycin‐induced fibrosis. Finally, we found that histone‐induced TGFβ1 from platelets modulated the T cell tropic cytokine production in macrophages.Our data suggest that NETs are an important factor for the pathogenesis of lung fibrosis. NETs may coordinate subsequent cytokine‐dependent interactions of platelets with innate and adaptive immune cells. In the future, pharmacologic blockade of NETs may be further evaluated as a potential treatment for chronic fibrotic diseases.Support or Funding InformationThis study was supported by the Federal Ministry of Education and Research (BMBF 01EO1503) and the Deutsche Forschungsgemeinschaft (BO3482/3‐1). The authors are responsible for the contents of this publication.
Allergen‐Induced Endoplasmic Reticulum Stress Regulates Lung Inflammation and Fibrosis
Authors: Mariswamy Siddesha Jalahalli , Nakada Emily M , Mihavics Bethany , Hoffman Sidra , Chapman David , Irvin Charles G , Dixon Anne , Poynter Matthew , Anathy Vikas 
Published: November 2023

BackgroundThe endoplasmic reticulum (ER) stress is known to play a critical role in many inflammatory diseases including asthma. One of the canonical responders of the ER stress, ATF6α is known to regulate inflammation in asthma. We have previously demonstrated that endobronchial biopsies from asthmatics and non‐asthmatics revealed a predominant increase in markers of ER stress in the asthmatic epithelium. These Increases positively correlated with higher eosinophil counts and bronchodilator response in asthmatics (Hoffman, S. et al., JACI, 2015‐in press). However, the mechanistic role of ER stress and ATF6α in asthma is not well understood.ObjectiveWe sought to examine the contribution of ER stress in the pathogenesis of allergic asthma, and the effect of a chemical chaperone tauroursodeoxycholic acid (TUDCA) in mitigating house dust mite (HDM)‐induced airway ER stress, inflammation and fibrosis.MethodsWe examined the markers of ER stress in asthmatic airway epithelium and utilized murine models of allergic asthma to evaluate the significance of upregulation of ER stress and evaluated the efficacy of TUDCA in mitigating allergic asthma.ResultsHDM‐challenge in mice resulted in robust increases in markers of ER stress including cleaved ATF6α as compared to Ovalbumin challenged mice. Wild type (WT) mice challenged with HDM showed a significantly higher influx of eosinophils and lymphocytes into the airways and to a lesser extent neutrophils and macrophages as compared to ATF6α−/− mice challenged with HDM. AHR measurements revealed that central airway resistance was significantly decreased in ATF6α−/− mice as compared to WT mice challenged with HDM. We also found increases in markers of fibrosis in HDM‐challenged WT mice as compared to HDM‐challenged ATF6α−/− mice.TUDCA administered during the HDM‐challenge phase (a prophylactic regimen) significantly decreased HDM‐induced markers of ER stress, airways inflammation, AHR and fibrosis as compared to control mice. Further, administration of TUDCA after the establishment of allergic airways disease, efficiently decreased HDM‐induced airways inflammation, mucus metaplasia, AHR and markers of UPR but not airway fibrotic remodeling.ConclusionOur novel results demonstrate that the markers of ER stress is increased in the airway epithelium of asthmatics and in mice with allergic airway disease. Specifically, deletion of ATF6, decreased pro‐inflammatory, fibrotic mediators, and AHR. We also demonstrate that a chemical chaperone mitigates the effects of allergen in a mouse model of asthma. These results suggest that inhibiting specific components of ER stress and strategies to utilize chemical chaperones may provide an opportunity to alleviate allergic asthma.Support or Funding InformationFunding: NIH R01 HL122383, Parker B. Francis Fellowship and Department of Pathology & Laboratory Medicine.
Dissection And Reconstitution Of Autophagic Membrane Fusion
Authors: Zhong Qing , Diao Jiaojie , Liu Rong , Rong Yueguang 
Published: November 2023

Autophagy, an important catabolic pathway implicated in a broad spectrum of human diseases, begins by forming double membrane autophagosomes that engulf cytosolic cargo and ends by fusing autophagosomes with lysosomes for degradation. Membrane fusion activity is required for early biogenesis of autophagosomes and late degradation in lysosomes. However, the key regulatory mechanisms of autophagic membrane tethering and fusion remain largely unknown. We recently reported that ATG14/Barkor/ATG14L, an essential autophagy‐specific regulator of the class III phosphatidylinositol 3‐kinase complex, promotes membrane tethering of protein‐free liposomes, and enhances hemifusion and full fusion of proteoliposomes reconstituted with the target (t)‐SNAREs (soluble N‐ethylmaleimide‐sensitive factor attachment protein receptors) syntaxin 17 (STX17) and SNAP29, and the vesicle (v)‐SNARE VAMP8. ATG14 binds to the SNARE core domain of STX17 through its coiled‐coil domain, and stabilizes the STX17‐SNAP29 binary t‐SNARE complex on autophagosomes. The STX17 binding, membrane tethering and fusion‐enhancing activities of ATG14 require its homo‐oligomerization by cysteine repeats. In ATG14 homo‐oligomerization‐defective cells, autophagosomes still efficiently form but their fusion with lysosomes is blocked. Recombinant ATG14 homo‐oligomerization mutants also completely lose their ability to promote membrane tethering and to enhance SNARE‐mediated fusion in vitro. Our data suggest an autophagy‐specific membrane fusion mechanism in which oligomeric ATG14 directly binds to STX17‐SNAP29 binary t‐SNARE complex on autophagosomes and primes it for VAMP8 interaction to promote autophagosome‐lysosome fusion. We are currently investigating protein factors and likely protein modifications required for full reconstitution of autophagosomal fusion with lysosomes.Support or Funding InformationThe work was supported by grants to Q. Z. from the Welch Foundation (I‐1864), CPRIT (RP140320), and NIH R01 (GM116908).
How Antibiotics Affect The Human Gut Microbiome: Lessons From The Extreme
Authors: Xavier Joao 
Published: November 2023

The intestinal microbiota is a symbiotic ecosystem of microbes that plays essential roles in human health. Microbes complement our ability to digest food by providing the genes and enzymes to break down complex nutrients but also keep gut pathogens out. We investigate how bacteria in the microbiota function together to make a healthy microbial ecosystem. By employing mathematical modeling techniques form ecology we could identify microbes and microbe‐microbe interactions that protect against enteric pathogens such as Clostridum difficile and vancomycin‐resistant Enterococcus (VRE). Our work suggests that mathematical modeling can be a valuable tool towards the rational design of antibiotic and probiotic therapies that tailor the microbiome to improve human health.Support or Funding Information

DP2OD008440/OD/NIH HHS/United States