bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estrogen replacement prevents ovariectomy‐induced muscle degradation via lowering local IGF‐1 production
Authors: Ezzat‐Zadeh Zahra , Navaei Negin , Akhavan Neda , Park Bong‐Sup , Chase P. Bryant , Kim Jeong‐Su , Arjmandi Bahram H. 
Published: June 2021

The prevalence of sarcopenia in women increases following menopause. Although muscle mass and circulating estrogens are positively correlated, the underlying mechanisms by which estrogen deficiency causes muscle atrophy is poorly understood. The present study examined the role of systemic and local IGF‐I in muscle maintenance of estrogen deficient rats. Eighteen 10‐month old female SD rats (n=6/group) were divided into either a sham operated group (sham) or two ovariectomized (ovx) groups receiving 17β‐estradiol (ovx+E2) or solvent vehicle (sham and ovx). All animals were pair‐fed for five months. Ovarian hormone deficiency did not cause atrophy in gastrocnemius (GAS) and soleus (SOL) muscle; however when muscle weight was normalized to body weight, the mean GAS value of ovx group was significantly lower than those of sham and E2 groups. Similarly, ovx mean SOL value tended (P<0.094) to be lower compared with other two groups. E2 treatment was able to prevent the ovx‐induced decreases in SOL, and GAS normalized values by 50% and 100%, respectively. Ovx significantly (P<0.05) increased systemic IGF‐I by 38% while local IGF‐I mRNA expressions were significantly decreased in both GAS (29%) and SOL (43%) samples of ovx rats. E2 administration prevented these decreases in IGF‐I levels. Our findings suggest that ovx‐induced elevation of systemic IGF‐I may down‐regulate its local mRNA expressions which in part can explain the loss of muscle mass in ovarian hormone deficiency.Grant Funding Source: Internal Funding
DHA dampens endocannabinoid tone related to cannabinoid receptor expression in proliferating C2C12 myoblasts
Authors: Kim Jeffrey , Li Yong , Alzghoul Borhan , Watkins Bruce A 
Published: June 2021

Emerging evidence indicates that the peripheral endocannabinoid signaling system (ECS) has a pronounced effect on health status, specifically glucose homeostasis. Focus on skeletal muscle is of great interest as it is a major storage for glycogen in the body. However, overactivation of the ECS in skeletal muscle has been shown to diminish insulin sensitivity. In particular, an elevation of CB1 activity has been reported in diabetic rodent models. Our research intends to identify changes in ECS tone by fatty acid (FA) enrichment. Proliferating C2C12 myoblasts were cultured until 50% confluency and treated with either 25 μM of AA, EPA, AEA, 2‐AG, or a BSA control for 24 h. Cells were collected and labeled with antibodies for CB1 and CB2 for FACS flow cytometry and FA analysis by GC. Compared to the control, FACS revealed a significant reduction in CB1 abundance with DHA treatment, while a significantly higher expression of CB1 was found with AA. No difference in CB2 level was observed. FA composition of myoblasts reflected their respective FA treatment. Interestingly, between the two AA‐derived ECS ligands, only 2‐AG enrichment had a doubling of its precursor, AA, but not with AEA. These findings suggest that DHA may dampen an overactive EC tone.Grant Funding Source: Diet and Health Initiative, UConn, Storrs, CT, USA
Recommended Dairy Intake: Impact on Lipid Profile and Surrogate Markers of Cholesterol Homeostasis in Healthy Adults from Two Canadian Cities
Authors: Abdullah Mohammad , Cyr Audrey , Couture Patrick , Jones Peter , Lamarche Benoît 
Published: June 2021

We assessed the impact of dairy intake on lipid profile and surrogate markers of cholesterol absorption, synthesis, and clearance in a free‐living, randomized, multicentre crossover trial of two 4‐wk dietary phases, DAIY and CONTROL, separated by a 4–8 wk washout, in Winnipeg and Quebec City, Canada. As part of a healthy‐style eating pattern, participants (n= 126) consumed 3 servings/d of conventional dairy products (375 ml/d low‐fat milk, 175 g/d low‐fat yogurt and 30 g/d regular cheddar cheese) or energy‐equivalent control products (290 ml/d fruit juice, 156 ml/d vegetable juice, 20 g/d cashews and 1 cookie). The DAIRY diet had no significant impact on circulating lipids, except for low density lipoprotein (LDL) levels, which were slightly higher relative to the CONTROL diet (2.98 vs. 2.90 mmol/L, P=0.03). This was accompanied by a reduction in plasma phytosterols’ levels (−11.0%, P<0.001), with no changes in lathosterol and proprotein convertase subtilisin/kexin‐9 (PCSK9) concentrations. These data indicate that the short‐term intake of DAIRY diet had possibly lowered cholesterol absorption, but not synthesis or clearance, in comparison to the CONTROL diet. Although plasma LDL levels were raised subsequent to the dairy consumption, the variability in the response of LDL (range: −1.29 to 1.03 mmol/L) across individuals suggested a genetic determinant. Supported by the Dairy Farmers of Canada.Grant Funding Source: Dairy Farmers of Canada
High‐dose (4000 IU) Vitamin D Supplementation Does Not Increase Circulating Concentrations of Free 25‐hydroxyvitamin D
Authors: Belenchia Anthony M , Tosh Aneesh , Hillman Laura , Peterson Catherine A 
Published: June 2021

Free/bioavailable circulating 25‐hydroxyvitamin D (25OHD) makes up a small fraction of total 25OHD concentration. We demonstrated the efficacy of a daily 4000 IU vit D dosage in raising total 25OHD concentrations of obese adolescents. However, it remained unclear whether the increase in total 25OHD was due to increases in the free form or that bound to vit D binding protein (DBP). The ratio of total 25OHD:DBP has been used as a proxy measure of free 25OHD. 44 patients (age=13.9; BMI =39.2) were recruited from the University of Missouri‐ADOBE clinic and were randomized to receive either placebo or vit D3 (4000 IU/day) treatment for 6 months. At baseline (BL), there was no difference between the vit D and placebo group in the ratio of 25OHD:DBP (0.19 vs 0.23; P=0.28). There no difference between groups in the change from BL (0.11 vs 0.05; P=0.10). There was a significant gender difference in the ratio at BL (M=0.17 vs F=0.12; P=0.015). Change from BL of total 25OHD was positively correlated with the change in the ratio (r=0.57; P<0.001) but not DBP(r=0.28; P=0.14). Supplementing obese adolescents with vit D3 does not increase free circulating 25OHD.Grant Funding Source: J.R. Albert Foundation, inc
Trends in Mineral Supplement Prescriptions from Military Treatment Facilities: 2007 to 2011
Authors: Attipoe Selasi , Jones Donnamaria , Stephens Mark B. , Deuster Patricia A. 
Published: June 2021

INTRODUCTIONMineral supplements (MS), such as calcium and iron, are readily available over the counter and are some of the most frequently consumed dietary supplements (DS). Healthcare providers also prescribe MS for treatment of certain conditions and maintenance of health. This study examines trends in MS prescriptions at Military Treatment Facilities (MTF).METHODSData from the Department of Defense (DoD) Pharmacoeconomic Center (PEC) was used to determine all MS prescriptions disbursed by MTF pharmacies between 2007 and 2011.RESULTSOverall, 1,797,982 calcium; 847,370 iron; 166,318 magnesium; and 23,297 zinc prescriptions were dispensed over this five‐year period. Whereas the number of zinc prescriptions decreased considerably by an average of 30% across the five‐year period, calcium and magnesium prescriptions increased slightly by 4% and 9%, respectively. Iron prescriptions dispensed were relatively stable across the five years.CONCLUSIONPatterns of MS prescriptions change over time. Whether the patterns within the DoD medical system are comparable to the civilian medical system is unknown. Also, it is not known whether the DS being prescribed are effective for the intended use.FUNDING:This study was supported by Center Alliance for Dietary Supplement Research (NA91FD).
Anti‐inflammatory effect of Spirluina platensis in macrophages is beneficial for adipocyte differentiation and maturation by inhibiting NF‐κB pathway in 3T3‐L1 adipocytes
Authors: Pham Tho Xuan , Lee Jiyoung 
Published: June 2021

We showed organic extract of Spirulina platensis, a blue‐green alga, (SPE) had potent anti‐inflammatory effects in macrophages. We hypothesize that by cross‐talking with adipocytes, the anti‐inflammatory effects of SPE in macrophages can be beneficial for adipocyte differentiation/maturation by inhibiting pro‐inflammatory cytokine production. Ten % conditioned medium from LPS‐stimulated RAW 264.7 macrophages (CMC) and LPS‐stimulated but SPE‐treated macrophages (CMS) were treated on 3T3‐L1 preadipocytes at different stages of differentiation. Expression of adipocyte differentiation markers, such as CCAAT/enhancer‐binding protein α, peroxisome proliferator‐activated receptor γ, and perilipin, was significantly repressed by CMC but attenuated by CMS. Oil Red O staining confirmed adipocyte maturation in CMS‐treated cells, but not CMC‐treated cells, were equivalent to control cells. Nuclear translocation of nuclear factor κB was attenuated by CMS compared to CMC. In lipid‐laden adipocytes, CMC promoted the loss of lipid droplets, while CMS had minimal effects. Histone deacetylase 3 and 9 are down‐regulated during the adipogensis, but CMS treatment reduced their abundance more than control. Our results show that SPE can promote adipocyte differentiation/maturation in inflammatory conditions, which otherwise can be compromised as in several metabolic disorders.Grant Funding Source: NIH R21AT005152
Mango polyphenols reduce inflammation in MDA‐MB231 breast cancer cell and targets MicroRNA‐21
Authors: Arbizu Shirley , Krenek Kimberly , Mertens‐Talcott Susanne 
Published: June 2021

Mango polyphenols have received some attention based on their antioxidant, anticarcinogenic and anti‐inflammatory properties. Our objective was to determine the anti‐inflammatory and cytotoxic properties of mango polyphenols (MP) in MCF12A non‐cancer breast fibroblasts and MDA‐MB231 breast cancer cells. mRNA, miRNA and protein expression of MDA‐MB231 and MCF12A cells were analyzed by real time PCR and Western blotting.Results show that MP (5mg of gallic acid equivalents/L (GAE/L)) decreased the proliferation of MB‐231 breast cancer cells by 90%; but not of MCF‐12A cells. In MB‐231 breast cancer cells, MP downregulated the expression of NF‐□B (to 0.6‐fold of the control), VEGF (0.5‐fold), TNF‐α (0.8‐fold), survivin (0.5‐fold) and Bcl2 (0.5‐fold). In MCF‐12A breast cells, MP downregulated TNF‐α‐induced expression of IL‐6 (0.8‐fold), IL‐1β (0.6‐fold) and NFKb (0.4‐ fold). miRNA 21 is up‐regulated in breast cancer and targets Bcl2 which is involved in apoptosis. MP reduced the expression the miR‐21 in a dose dependent manner and these findings were confirmed using the specific antagomir for miR‐21, where it reversed the effect of the polyphenolic treatment in MB‐231 cells.These results indicate that the cytotoxic effects of mango polyphenols are specific to cancer cells where inflammation was reduced in both, cancer and non‐cancer cells, seemingly through the involvement of miR‐21.Grant Funding Source: Research Assistanship
Anti‐inflammatory activity and metabolism of α‐mangostin by cells of human origin
Authors: Gutierrez‐orozco Fabiola , Chitchumroonchokchai Chureeporn , Lesinski Gregory B , Failla Mark L 
Published: June 2021

Xanthones in mangosteen (Garcinia mangostana), a fruit native to Southeast Asia, have been reported to exhibit anti‐proliferative and pro‐apoptotic activities. Recent data from our laboratory suggest ingested xanthones and their metabolites are absorbed and delivered to tissues where they may be accumulated and further metabolized. Neither the anti‐inflammatory activity of xanthones for cells of human origin nor the metabolism of these compounds by animal or human cells have not been examined with the exception of our previous studies with Caco‐2 human intestinal cells. We have found that ≤15 μM α‐mangostin (α‐MG), the most abundant xanthone in mangosteen, suppresses secretion of a) IL‐8 by activated human Caco‐2 intestinal, HT‐29 colonic, and THP‐1 macrophage‐like cell lines, and b) TNFα by activated HepG2 and human blood monocyte‐derived macrophages. α‐MG was taken up and metabolized by the various cell types and results with Caco‐2 suggest bioavailability may be enhanced during inflammatory conditions. Furthermore, unconjugated xanthones were predominant in HepG2, THP‐1 and HT‐29 cultures in the pro‐inflammatory environment. In addition to glucuronidation/sulfation of α‐MG, conversion to 9‐hydroxycalabaxanthone, garcinones C and D, and other unknown xanthone compounds was observed. Ongoing studies are examining anti‐inflammatory activity of α‐MG using a preclinical model.Grant Funding Source: OSU FIC and Conacyt Fellowship (Mexico)
Innate immune sensing of a bacterial protein in the ER by IRE1α
Authors: Cho Jin Ah , Lencer Wayne 
Published: June 2021

The plasma membrane and all membrane‐bound organelles except for the Golgi and endoplasmic reticulum (ER) are equipped with pattern‐recognition molecules to sense microbes or their products and induce innate immunity for host defense. Here, we report that Inositol‐REquiring‐1α (IRE1α), an ER protein that signals in the unfolded protein response (UPR), is activated to induce inflammation by cholera and Shiga toxins as they co‐opt the ER to cause disease. Other known UPR transducers, including the IRE1α effector XBP1 are dispensable for this signaling. The inflammatory response depends instead on the RNase activity of IRE1α and retinoic‐acid inducible gene 1 (RIG‐I), a cytosolic sensor of RNA fragments. These observations implicate Regulated IRE1α‐Dependent Decay of mRNA (RIDD) in a novel innate immune mechanism of host defense originating from within the ER lumen.Grant Funding Source: NIH R01/CCFA
Ω‐3 Fatty Acid Effects on Obese Leptin Knock‐Out Mice
Authors: Ali Arfaa , Nachnani Jagdish , Bulchandani Deepti , Alba Laura , Mansour Ahmad , Hamdan Hana , Quinn Tim , Molteni Agostino , Herndon Betty 
Published: June 2021

Liver steatosis in wild‐type rats on methionine‐choline deficient diets is decreased with fish oil (Nachnani, Diabetologia 53:153,2010). Effects of Ω‐3 fatty acid were studied here in OB/OB (leptin k/o) mice with natural obesity and steatosis. Ten mice received purified Ω‐3 (20% EPA, 50% DHA) in food pellets, equivalent (mg/kg) to a human dose of ~4 grams/day. Ten more OB/OB mice received corn oil in their food. At 60 day necropsy, livers were harvested for study. Five Ω‐3 treated mice survived and unexpectedly blood glucose of >;600 mg/dL was found in 3 of them. Since leptin receptor k/o mice (DB/DB) are diabetes models, liver homogenate and sera of Ω‐3 and controls were analyzed for murine leptin receptor (ELISA), but no difference was found between groups. Ω‐3 treated mice showed reduced fatty liver infiltration, 27.6% Ω‐3 and 38.5% untreated, with less periportal and portal triad inflammation in Ω‐3 mice. Heart histopathology showed irregular, eosinophilic myocardial fibers with pyknotic nuclei, suggesting necrosis. Such changes in heart cell morphology is reported in human diabetes. Sera showed significant lowering of insulin, IL‐6, adiponectin, and TNFα in the Ω‐3 group compared to untreated. Ω‐3 fatty acid treatment may reduce liver steatosis in OB/OB mice but other physiological changes with diabetes induction may limit its use as a model.Funded: St. Luke's Foundation, Kansas City
Plasma protein protects endothelial glycocalyx mediated by sphingosine‐1‐phosphate
Authors: Zeng Ye , Adamson Roger , Curry Fitz‐Roy , Tarbell John 
Published: June 2021

It has long been known that albumin reduction in endothelial cell (EC) media induces collapse or shedding of the surface glycocalyx layer. This leads to impairment of the endothelial transport barrier and other features of vessel homeostasis. The electrostatic interaction between arginine residues on albumin and negatively charged glycosaminoglycans in the glycocalyx has been hypothesized to stabilize the glycocalyx structure. But sphingosine‐1‐phosphate (S1P), which is bound to albumin, also plays important roles in maintaining vascular barrier integrity and homeostasis. Here, the role of S1P in maintaining glycocalyx stability was investigated in this study. Using confocal microscopy on EC in vitro, we observed that heparan sulfate (HS), chondroitin sulfate (CS) and the ectodomain of syndecan‐1 were shed from the surface after removal of plasma protein, but were retained in the presence of S1P or a general MMP inhibitor. S1P receptor 1 (S1P1) antagonism abolished the protection of the glycocalyx by S1P. GAGs released to culture media and the general MMP activity increased significantly after removal of plasma protein, but could be diminished by S1P. Thus, S1P plays a critical role in protecting the glycocalyx via S1P1, and inhibits the protease activity‐dependent shedding of CS, HS and the syndecan‐1 ectodomain. Our results provide new insight into the role for S1P in protecting the glycocalyx and maintaining vascular homeostasis.Grants: Supported by NIH Grant HL094889 and HL 28607.
Role of Thrombospondin‐1 In the Remodeling Induced by a Chronic Increase in Flow in Resistance Arteries
Authors: Grenier Céline , Caillon antoine , Grimaud Linda , Ayer Audrey , Toutain Bertrand , Blanc‐Brude Olivier , Henrion Daniel , Loufrani Laurent 
Published: June 2021

BackgroundChronic increases in blood flow in resistance arteries induce outward vascular remodeling due to increased NO‐dependent dilation and MMP activation. Although thrombospondin‐1 (TSP‐1) interacts with a variety of matrix proteins and cell‐surface receptors, controversy remains about its vascular functions. We investigated the role of TSP‐1 in high flow (HF)‐mediated remodeling of resistance artery.Material and methodsMesenteric arteries were ligated in vivo in order to generate high‐flow arteries compared with normal flow (control) vessels located at distance on wild type (WT) and TSP‐1 deleted mice (TSP‐1 KO). Arteries were isolated 4 days to 1 week after ligature. Diameter and arteries reactivity were studied in vitro in an arteriograph. Genes implicated in inflammation and immune cells recruitment were determined in HF and NF arteries.ResultsArteries remodeling, due to high flow (found in WT), were not significant in TSP‐1 KO arteries. Dilatory (sodium nitroprusside) and contractile (Phenylephrine) tone, were unaffected by the absence of TSP‐1.We also demonstrated, after 4 days of ligature, an increase in CD68, Cox1, Cox2, Gp91phox, p47phox, p22phox, expression level between NF and HF WT arteries that was not observed in KO arteries.Furthermore, we also observed a increase in neutrophils and lymphocytes number in response to chronic high flow in WT arteries, not observed in HF KO arteries.ConclusionThe absence of TSP‐1 induced a decrease in flow‐induced remodeling with a reduction of the inflammatory response and of the endothelium‐mediated dilation involved in HF remodeling.
Neutrophil depletion attenuates placental ischemia‐induced hypertension in rat
Authors: Lillegard Kathryn E , Bauer Ashley J , Johnson Alex C , Lojovich Sarah J , Gilbert Jeffrey S , Regal Jean F 
Published: June 2021

Preeclampsia is characterized by compromised placental perfusion and hypertension during pregnancy. Preeclamptic women exhibit a greater number of neutrophils (PMN) in the vasculature and a decrease in plasma free vascular endothelial growth factor (VEGF) compared to normal pregnancy.HypothesisPMN are critical to placental ischemia‐induced hypertension and decreased VEGF. Using the reduced uterine perfusion pressure (RUPP) model of placental ischemia‐induced hypertension, we determined the effect of PMN depletion on blood pressure and plasma VEGF. PMN were depleted with repeated injections of polyclonal rabbit anti‐rat neutrophil antibody (αPMN). On gestation day 14, clips were placed on the abdominal aorta and uterine arteries to decrease placental perfusion. RUPP and Sham rats received either αPMN or normal rabbit serum (Ctl) on gestation days 13, 14, 16, and 18, and mean arterial pressure (MAP) was measured via arterial catheter on day 19. PMN‐depleted rats had reduced circulating PMN (p<0.05) on day 14 compared to Ctl. MAP increased (p<0.05) in RUPP Ctl vs Sham Ctl rats, and PMN depletion attenuated this increase in MAP in RUPP rats (p=0.04) without any effect on Sham rats. The RUPP‐induced decrease in VEGF was not affected by PMN depletion. Thus, neutrophils are important in placental ischemia‐induced hypertension independent of plasma free VEGF concentrations. Support: NIH R15 HL109843.
Decoding Ubiquitin Networks in regulation of inflammation and autophagy
Authors: Dikic Ivan 
Published: June 2021

Ubiquitin acts as a cellular signal that is decoded by its receptors to control normal functioning of the cell via different linkage types. Using the different structural and biochemical properties of different ubiquitin chain linkages, we have developed fluorescence‐based sensors to monitor real‐time localization and dynamics of ubiquitination events in vivo. For example, linear chain‐specific sensors labeled the ubiquitin coat surrounding cytosolic Salmonella and were also able to block TNF‐induced NF‐κB activation; whereas K63‐sensors were enriched at DNA double strand breaks and depolarized mitochondria following Parkin recruitment.In addition to sensors that detect linkage‐specific ubiquitin chains, we have been exploring the fate of intracellular pathogens and how they are targeted by the host autophagy system. Removal of harmful protein aggregates, damaged organelles and microbes is mediated by autophagy, a process by which the cell sequesters cytosolic cargo and delivers it for degradation by the lysosome. Optineurin, a new autophagy receptor, together with p62 and NDP52, mediates selective autophagy of ubiquitin‐coated cytosolic Salmonella enterica. The protein kinase TBK1 (TANK binding kinase 1) was shown to mediate phosphorylation of both LC3‐ and Ub‐binding domains to ensure a rapid engulfment of cytosolic bacteria and efficient autophagic clearance.
Antagonistic roles of CD14 and TLR4 in LPS‐induced colonic epithelial cell apoptosis
Authors: Kuo Wei‐Ting , Yang Hsun‐Yuan , Chen Chi‐Yun , Lu Yen‐Zhen , Ni Yen‐Hsuan , Yu Linda Chia‐Hui 
Published: June 2021

Luminal exposure to bacterial LPS induces apoptosis in intestinal epithelial cells via unknown mechanism. Recent studies in monocytes showed that after LPS binding to CD14, phosphatidylcholine‐specific phospholipase C (PC‐PLC), SMase and ceramide activate PKCζ, and recruits TLR4 for complex formation and downstream MAPK and NFκB signals.AimTo investigate the receptors and signaling pathways involved in LPS‐induced epithelial apoptosis.ResultsApical expression of CD14, low levels of MD2, and absence of TLR4 were demonstrated in primary human colonocytes and Caco‐2 cells. Luminal LPS challenge increased cell apoptosis, which may be inhibited by anti‐CD14 or gene silencing of CD14 and PKCζ, but not anti‐TLR4. Inhibitors to PC‐PLC, SMase and PKCζ decreased apoptotic levels. CD14‐mediated ceramide and phospho‐PKCζ levels were increased after LPS challenge, whereas TLR4 signals were not. TLR4 overexpression by plasmid transfection inhibited LPS/CD14‐mediated apoptosis. Moreover, both CD14 and TLR4 were found on mouse colonocytes. Colonic tissues of TLR4‐mutant mice exposed to luminal LPS or bacterial overgrowth display increased mucosal apoptosis and phospho‐PKCζ compared to wild types.ConclusionsLPS‐induced epithelial apoptosis was dependent on CD14‐mediated lipid secondary messengers, whereas TLR4 plays an antagonistic role. Funding support by National Science Council and NTU.