bluuebunny/crossref_metadata_2025_split huggingface dataset:
MiR‐383 Is Associated With Ameliorated Hepatic Steatosis In Mice Fed On High‐Fat Diet
Authors: Yan Biao , Duan Xiaomei , Shi Yonghui , Le Guowei 
Published: November 2023

Non‐alcoholic fatty liver disease (NAFLD) is the hepatic component of the metabolic syndrome and characrized by excess accumulation of triglycerides in the liver in the absence of alcohol consumption, yet the underlying molecular mechanisms remain poorly understood. Here we fed the mice with normal chow (NC) or high‐fat diet (HFD) and screened the obesity‐prone (OP) mice and obesity‐resistant (OR) mice in HFD group. We found HDL in plasma is significantly decreased in OP mice, but no difference between NC mice and OR mice. Oil red O staining revealed the accumulation of triglycerides in NC mice and OR mice are much less than OP mice. We also found the expression level of FAS is upregulated in the liver of OP mice, while the expression level of CPT1a and PGC1a is upregulated in the liver of OR mice compared with the NC mice, suggesting the enhanced steatolysis in OR mice. To understand the mechanism underlying NAFLD, we examined the liver miRNA expression in NC, OP and OR mice by next‐generation sequencing and found enhanced miR‐383 level in OP mice rather than OR mice. Thyroid hormone plays an important role in regulating hepatic lipophagy and we found DIO1 gene which activates thyroid hormone by coverting T4 to T3 is the target gene of miR‐382 and its expression level is upregulated in OR mice. Correlated with the elevated DIO1 expression in OR mice, the T3 level of OR mice is also higher than OP mice. Overall, our data suggest that miR‐383 may contribute to ameliorated hepatic steatosis in OR mice by targeting DIO1 gene in liver, and provide a potential molecular target for NAFLD therapeutic strategies.Support or Funding InformationThe study was supported by the 12th five‐year plan for science and technology development(No. 2012BAD33B05).
GC‐TOF/MS‐based Metabolomic Profiling of Goto‐Kakizaki (GK) Rats: Comparison of Diets Enriched with Purified Resistant Starch or Resistant Starch in the Form of Whole‐Grain Flour
Authors: Martin Roy Joseph , Fahrmann Johannes , Carvajal‐Aldaz Diana , Guice Justin , Page Ryan , Raggio Anne , Coulon Diana , Stout Rhett , Pelkman Christine , Marco Maria L. , Keenan Michael J 
Published: November 2023

Dietary resistant starch has been shown to have profound effects on gut microbiota resulting in enhanced short chain fatty acids, elevated gut peptides and improved metabolic syndrome. The aim of this study was to investigate the serum metabolomic response to dietary purified resistant starch and resistant starch in the form of whole‐grain flour in GK rats, a non‐obese type 2 diabetes model. GK rats were put in four diet groups (n=12 per group) (1) control starch with no WG or RS [CON], (2) purified HAMRS [RS], (3) WG waxy corn flour with low RS [WG], and (4) WG HAMRS flour [WG+RS]. Each of these was fed for 12 weeks. Post 12 weeks, serum was collected and metabolomics analysis was conducted using gas chromatography time‐of‐flight mass spectrometry to identify 327 compounds of which 154 had known annotations. Univariate analysis indicated 54 metabolites significantly differential (pFDR<0.05) amongst the dietary groups. The most pronounced metabolic perturbations were found in WG+RS group, followed by RS group, relative to control. Orthogonal partial least squares discriminant analysis (O‐PLS‐DA) multivariate models were used to identify the top 10% of all metabolite discriminants between the dietary groups. Top discriminatory metabolites included 1) microbiome‐derived indole‐3‐lactate, indole‐3‐acetate and 3,4‐hydroxyphenol‐propanoic acid, 2) citrate, a TCA‐intermediate and important precursor for de novo lipogenesis and 3) primary bile acid cholic acid; all of which were increased in RS, WG and WG+RS diets relative to control. These findings provide unique insight into metabolic alterations attributed to starch resistance and whole‐grain effects and cumulatively point towards alterations in bile acid biosynthesis and the gut microbiome.Support or Funding InformationDanish Council for Strategic Research, Ingredion and LSU AgCenter.
Associations between Weight‐Related Variables, Gender, and Age in Overweight and Obese Preadolescents and Adolescents
Authors: Delavan Elizabeth Leigh , Crook Tina , Phelps Josh , Hakkak Reza 
Published: November 2023

Despite the increased awareness and attention targeted toward the childhood obesity epidemic, a feasible and ideal treatment strategy remains a challenge. The literature suggests that weight loss attempts in overweight/obese children and adolescents are more successful when they have a desire to lose weight and have a correct perception of their weight status. Thus, the objective of this study was to examine “desire to lose weight” and “weight perception accuracy” in children, ages 8–15 years. Data from NHANES 2011–2012 were used for the analyses. Participants included 548 overweight and obese preadolescents (8–11 years of age) and adolescents (8–15 years of age). BMI category was determined by physical examination data and CDC age‐ and gender‐specific growth charts. NHANES questionnaire responses were used to determine weight perception accuracy, desire to lose weight (based on what participants reported they were trying to do about their weight), and identification as overweight by a health professional. Chi‐square tests were performed to determine independence of variables. Data showed significant associations between desire to lose weight and identification of overweight by a doctor or health professional, χ2 (1) = 33.544, p = <.0001, phi = .258, weight perception accuracy and age, χ2 (1) = 17.363, p = <.0001, phi = .186, weight perception accuracy and diagnosis of overweight by a doctor or health professional, χ2 (1) = 56.281, p = <.0001, phi = .332, and weight perception accuracy and gender, χ2 (1) = 3.957, p = .047, phi = .091. Our results indicate that identification of childhood overweight/obesity by doctors and other health professionals is a key component to effective treatment. Additionally, the treatment strategy should take into consideration the age and gender of the child. Based on our findings, we advocate that a “one‐size‐fits‐all” method for the treatment of childhood overweight and obesity is likely oversimplified and insufficient.Support or Funding InformationDepartment of Dietetics and Nutrition, University of Arkansas for Medical Sciences
Healthy as a Horse
Authors: Battisti Helen , Battisti Francis 
Published: November 2023

ObjectiveThis prospective cohort pilot study was designed to examine the impact of Equine Assisted Learning (EAL) on long‐term weight management during childhood.MethodsEquine Assisted Learning (EAL) is a standardized learner‐centered experiential education methodology, featuring the partnership between horses and humans. Two cohorts of overweight and obese children (total n=17 females, 9.8±1.0 y, 94.2±3.6 percentile BMI‐for‐age) were recruited for the Healthy as a Horse (HaaH) program from family practice and pediatric medical offices throughout Broome and Tioga Counties in upstate New York. Participants and their families received education in the following areas: equine care and riding, human nutrition, communication, stress management, leadership, team development and healthy lifestyle change. Participants’ baseline (BL) data was collected at the start of the program and after one year, and included anthropometrics (height, weight) and body composition analysis via Dual‐Energy X‐ray Absorptiometry.ResultsThirteen participants among the 2 cohorts had complete body composition data at BL and 1 year. In the total sample (n=13), there was a trend for change in body fat to be associated with both BL body weight (r=0.53, p=0.06) and age (r=0.55, p=0.10). Mean BL height and body weight of the first (n=5) and second (n=8) cohorts differed (59.5±1.1 vs 53.8±5.8 in, p=0.05 and 129.8±14.2 vs. 101.0±21.0 lb, p=0.02, respectively), and children in the first cohort tended to be older (10.3±1.2 vs. 9.3±0.5 y, p=0.09), and thus analyzed separately. Children completing cohort 1 did not gain body weight over the 1 y, and there was a trend for a decreased BMI‐for‐age percentile (−3.4±3.0 percentile points, p=0.06). Children in cohort 1 also significantly decreased their total percent body fat over the 1y study (−2.8±2.2%, p=0.05). In cohort 2, participants gained a significant amount of body weight (10.0±7.6 lb, p=0.007), and their body fat increased over the 1 y period (+2.1±2.3, p=0.03).ConclusionResults from the two separate cohorts of the HaaH pilot study demonstrate a unique opportunity to further examine the use of the horse as a tool to assist in the continued development of effective programs to prevent, identify and treat childhood overweight and obesity. A randomized controlled trial is needed to explore if the observed differences in the body composition changes between cohorts 1 & 2 are the result of the interactions with the horse or the result of the EAL methodology. A higher BMI‐for‐age during childhood is associated with earlier onset of pubertal maturation, and we have observed different trends between cohorts regarding total body fat as well as body fat distribution. Future studies will need to include the Tanner Scale to better estimate pubertal maturation in order to control for its possible influence on change in adiposity in this type of intervention.Support or Funding InformationThe Stanley H. and Theordora L. Feldberg Foundaton
Soybean‐derived glyceollins promote Nrf2‐mediated detoxifying enzymes in colorectal cells
Authors: Jo Gwangrae , Oh Jisun , Kang Sujin , Kim Minsun , Jang Jinho , Jeong Gain , Seo Hyelin , Ju Sunghee , Woo Yaejin , Lim Soonsung , Kim Jong‐Sang 
Published: November 2023

Glyceollins are soybean‐derived phytoalexins and synthesized upon exposure to some types of fungus. Glyceollins can induce antioxidant and phase II detoxifying enzymes and thus prevent some types of tumors induced by chemical carcinogens. However, little is known about if glyceollins influence the redox system in colon cells. In this study, we investigated whether phase II detoxifying enzymes and oncoproteins are differentially expressed by glyceollin treatment in colorectal cell lines. HCT116 (p53‐positive), HT29 (p53‐null), and Caco‐2 (p53‐negative) cells were treated with glyceollins. The mRNA and protein expression levels of Nrf2‐associated redox enzymes (NRF2, Keap1, HO‐1, GR, and NQO1) and oncoproteins (p53 and p21) were examined. Our results show that (i) glyceollin treatment induced Nrf2 mRNA expression and its nuclear translocation in colon‐derived cells, (ii) glyceollin treatment augmented NQO1 expression and activity, and (iii) mRNA levels of Nrf2 and oncoproteins were remarkably increased in glyceollin‐treated, p53‐positive cells, but not in p53‐compromized cells. These findings demonstrate that glyceollins could modulate cellular redox system by inducing Nrf2‐associated enzymes, and a tumor suppressor p53 may boost up the Nrf2 induction. It suggests the potential preventive activity of glyceollins against colon tumorigenesis.Support or Funding InformationThis work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (Project No. 2014R1A2A2A01005773)
Potential Pathological Implication of Osteocalcin and Vitamin D in Acute Aortic Dissection
Authors: ROMANELLI MASSIMILIANO MARCO CORSI , VIANELLO ELENA , BARASSI ALESSANDRA , TRIMARCHI SANTI , DOZIO ELENA 
Published: November 2023

Introduction and aimAcute aortic dissection (AAD) is a cardiovascular disease (CVD) associated with high morbidity and mortality. Extracellular matrix fragmentation and death of vascular smooth muscle cells within the aortic wall are early features of AAD. Although the pathogenetic mechanisms leading to these alterations have not been clarified yet, impaired endothelial function is considered a potential link between different CVD risk factors and AAD. Recently, vitamin D and the bone turnover marker osteocalcin (OC) emerged as CVD‐related molecules, mainly due to their involvement in endothelial damage, inflammation and vascular calcification. The evaluation of the potential implication of these molecules in AAD is the aim of our study.MethodsSerum samples of 24 AAD patients were obtained within 24 h of symptom onset. OC and vitamin D concentration (25OHD) were measured by chemiluminescent immunoassay methods (LIAISON®, DiaSorin). Data are presented as mean ± standard deviation (SD). The t‐test was used to compare groups. Relationship among variables was assessed by the Spearman correlation analysis. A p value < 0.05 was considered statistically significant.ResultsIn AAD patients, mean OC level (17.95 ± 1.66 ng/mL) was within normal range, on the contrary mean 25OHD concentration (12.63 ± 6.93 ng/mL) was indicative of hypovitaminosis D. None of the patients had 25OH level > of the cut off value of 30 ng/mL, sometimes used for optimal vitamin D status. Among patients, 38% had 25OHD level < 10 ng/mL, 38% in the range 10–20 ng/mL and 24 % > 20 ng/mL. OC level was reduced in patients with the highest 25OHD concentration (> 20 ng/mL) compared to patients with 25OHD deficiency (< 10 ng/mL). Moreover, we observed an inverse association between OC and 25OHD (r = −0.61, p < 0.01).After patients classification according to dissection localization (ascending aorta, type A, or descending aorta, type B), mean 25OHD and OC levels were, respectively, higher and lower in type B compared to A, anyway just over the limit of statistical significance. None of type B patients displayed 25OHD deficiency.ConclusionsIn AAD reduced 25OHD level was associated to increased OC concentration. Both molecules might thus be involved in AAD. The evaluation of their relationship with traditional cardiovascular risk factors and markers of endothelial dysfunction will be helpful to better clarify the role of 25OHD and OC in AAD and the potential associated pathophysiological mechanisms.Support or Funding InformationStudy was supported by DiaSorin S.P.A., Vercelli, Italy.
Bone morphogenic protein 2 is a key regulator of spheroidal aggregates of mesenchymal stem cells
Authors: Tamama Kenichi , Funnell Jessica , Cesarz Zoe 
Published: November 2023

Cell therapy with adult mesenchymal stem cells (MSCs) is a promising approach in regenerative medicine and autoimmune disease. There are various approaches to improve the efficacy of MSC‐based therapeutics, and MSC preparation as spheroidal aggregates or MSC spheroids is a novel preparatory and delivery method. Spheroid formation induces a dramatic change in the gene expression profile of MSCs. Self‐activation of interleukin‐1 (IL1) signaling was shown to be upstream of both pro‐ and anti‐inflammatory genes in MSC spheroids, but the molecular pathways that initiate IL1 signaling remain unknown. As BMP2 up‐regulation precedes that of IL1B expression during spheroid formation, we hypothesized that BMP2 signaling triggers IL1 signaling in MSC spheroids. Contrary to expectations, BMP2 signaling decreased expression of IL1B and downstream genes in a SMAD6‐dependent manner. Conversely, IL1B signaling enhanced BMP2 expression. Another major difference between 2D monolayer culture and 3D spheroid culture is the Young's elasticity modulus, or stiffness, of the materials surrounding the cells, as there is a million‐fold difference between a plastic surface for standard 2D culture (GPa) and 3D spheroidal aggregate (0.1 kPa). We tested another hypothesis that soft elasticity‐associated mechano‐signaling functions as a regulatory mechanism in the early phase of spheroid formation. Both BMP2 expression and inflammatory signaling are up‐regulated in an elasticity‐associated signaling dependent manner in MSCs. Finally, BMP2 signaling enhanced cell survival and cell spreading of MSC spheroids. In summary, our study suggests that BMP2 is a key regulator of MSC spheroids.Support or Funding InformationThis study was supported by University of Pittsburgh Schools of Health Sciences (Bridge Funding Category One), University Pittsburgh Medical Center Health System (Competitive Medical Research Fund), and departmental funds (Department of Pathology, University of Pittsburgh School of Medicine)(to KT) and University of Pittsburgh School of Medicine Summer Undergraduate Research Program (SURP) (to JF).
A New Composite Biomarker for Cervical Cancer Diagnosis
Authors: Markovic Olivera , Markovic Nenad 
Published: November 2023

In 2004, at the FASEB meeting, we introduced our new proprietary, biomarker‐based MarkPap® technology for detection of abnormal cells on cervical specimens.At subsequent meetings, we followed with reports for further developments of this platform technology, e.g., semi automated processing, diagnosis at distance with digital (TelePap) and mobile (Mobile Pap) transmission of microscopic images from POC to medical centers. Empowering the methodology with IT technology (telecytopathology) it became infrastructure‐independent and a possibility for self‐specimen collection (MarkPap Self) opened a prospective for global cervical cancer screening.On the most recent FASEB meetings we presented our results from building IT Telehealth Center for Telecytopathology with proprietary communication network to a global networking system enabling automatic exchange of secure digital image (high resolution, still, metadata) files between POCs and medical centers for the purpose of global cervical cancer screening.This time, we are presenting a composite, meaningful biomarker MEDYKO, an acronym, composed of ME ‐ pre‐malignant changes (cervical acid phosphatase); DY‐dysplasia, dyskaryosis (malignancy); KO – koilocytes, HPV disease (poor prognosis). This composition of biomarkers provides instant visual information of the metabolic status of cell undergoing transformation, morphological status of the nucleus indicating DNA malignant alteration, and koilocytes indicating poor prognosis because of the chronic HPV disease. All three parameters were present in high percent of cases of advanced cervical cancer and hierarchically less expressed in HSIL, LSIL and ASCUS.These results warrant further work on multiple biomarkers related to malignant disorders, which instant recognition on Pap smears could improve the clinical value of such new Pap test and return it to prior status of the “best anticancer screening test available”.Support or Funding InformationBioSciCon, Inc.
Foxi3: A Sly Regulator of Bone Development, Promotes Prostate Cancer
Authors: Mukherjee Angana 
Published: November 2023

Prostate cancer is the abnormal growth of cells in the prostate gland, and is the second leading cause of deaths among men in the United States. Studies have shown that 100% of men that die from prostate cancer have bone involvement. It is believed that tumor cells take on a bone phenotype, termed osteomimicry, thus permitting its growth at an ectopic location. Of the many cells resident in the bone, myeloid cells secrete various soluble factors that contribute to the high turnover rate of cells and molecular processes of bone development. Of particular interest, foxi‐3, a forkhead family transcription factor is critical in bone development and embryogenesis. However, its role in prostate cancer, has not been explored. Therefore, we hypothesized that foxi3 is a key factor in promoting prostate cancer progression to the bone. To investigate the clinical role of foxi3, we analyzed its expression and localization in human prostate cancer tissue and cell lines. Interestingly, there is a significant increase in foxi3 expression as cancer becomes more aggressive (p<0.01). Moreover, we see a 6000‐fold increase in foxi3 expression in bone metastatic cells than primary tumor cells. Furthermore, treatment with fibroblast growth factor, a regulator of bone development, resulted in differential expression and localization of foxi3 and bone markers in prostate cancer. Taken together, these data suggest a crucial role for foxi3 in prostate cancer progression to the bone.Support or Funding InformationTroy University Faculty Development Grant ‐ 0409365
Breast Tumor Development and Cigarette Smoking: Accelerated Tumor Development in Calcium Independent Phospholipase A2γ Deficient Mice
Authors: Kispert Shannon E , McHowat Jane 
Published: November 2023

The phospholipase A2 (PLA2) family of enzymes are responsible for cleavage of membrane phospholipids, releasing a free fatty acid and lysophospholipid. Various PLA2 dependent pathways are important in regulation of cell proliferation, differentiation, motility, and immune responses which can all be altered during tumor development and progression. Calcium independent PLA2 (iPLA2) enzymes are responsible for phospholipid remodeling as well as release of arachidonic acid or lysophosphatidic acid (LPA) which play major roles in downstream signaling pathways. The most commonly studied iPLA2 enzymes are iPLA2β and iPLA2γ, but their role in cancer development remains unknown. To determine what effects cigarette smoke exposure had on mammary tissue from wild type and iPLA2γ deficient mice, we exposed six month old females to cigarette smoke using the SCIREQ InExpose system for up to six months. Mammary tissue was removed and snap frozen for biochemistry or stored in formalin for immunohistochemical analysis. Following three and six months of cigarette smoke exposure, wild type mice showed atypical ductal hyperplasia. In comparison, the iPLA2γ knockout mice developed ductal carcinoma in situ following three months of cigarette smoke exposure. Recent studies from our lab have determined that iPLA2γ deletion in mice results in alterations of cytokine expression implicated in breast tumor progression when compared to wild type mice. Changes in cytokine expression may elucidate the mechanism by which iPLA2γ deficient mice develop tumors more rapidly than wild type mice in the presence of cigarette smoking.Support or Funding InformationSaint Louis University Presidents Research Fund
Anti‐invasive activity of capsaicin and non‐pungent capsaicin analogs in human SCLC
Authors: Akers Austin T , Hurley John D , Brown Kathleen C , Nolan Nicholas A , Dasgupta Piyali 
Published: November 2023

Small cell lung cancer (SCLC) is the most aggressive lung malignancy. A majority of SCLC patients show extrapulmonary metastasis at the time of their presentation. The common sites of SCLC metastasis are bone and the brain. The invasion of malignant cells to the neighboring blood vessels and lymph nodes is a key step of metastasis. Recent data indicate that dietary compounds (by themselves or in combination with standard chemotherapy) reduce invasion and metastasis of several human cancers. Capsaicin is the pungent ingredient of chili peppers. Recent studies have shown that capsaicin inhibits the invasion and metastasis of several types of human cancers including melanoma, prostate cancer and cholangiosarcoma. We tested the anti‐invasive activity of capsaicin, as well as two non‐pungent capsaicin analogs, olvanil and arvanil, in human SCLC using the Boyden chamber assay and spherical invasion assay. We found that olvanil and arvanil possess greater anti‐invasive activity than capsaicin. The biological activity of capsaicin is mediated by transient receptor potential vanilloid (TRPV) receptors on target cells. However, arvanil and olvanil bind to both TRPV and cannabinoid receptors. Boyden chamber and spherical invasion assay revealed that the anti‐invasive effects of capsaicin, olvanil and arvanil were independent of both TRPV and cannabinoid receptors. The capsaicin analogs olvanil and arvanil may prove useful for the management and treatment of SCLC metastasis.Support or Funding InformationFunding for our study was supported by the an NIH R15‐AREA Grant (1R15HL113681‐01A1), AICR Investigator Grant, and a NASA Undergraduate Fellowship to ATA.