bluuebunny/crossref_metadata_2025_split huggingface dataset:
An Atherogenic Diet Exacerbates Vascular Injury in an Experimental Model of Systemic lupus Erythematosus
Authors: Coleman Taylor , McClung Daniel , Ryan Michael J , Taylor Erin B 
Published: June 2021

Patients with systemic autoimmune diseases such as systemic lupus erythematosus (SLE) have an increased risk of developing premature atherosclerotic cardiovascular disease (CVD), which is a major contributor to morbidity and mortality in this patient population. Specifically, patients with SLE have evidence of vascular disease including endothelial dysfunction, arterial stiffness, and coronary perfusion abnormalities, all of which predispose them to the development of atherosclerotic lesions. Our laboratory has shown that an established female mouse model of SLE (NZBWF1) develops impaired endothelial dependent relaxation compared to age matched healthy controls (female NZW mice). In the present study, we hypothesized that SLE mice fed an atherogenic diet will have accelerated vascular injury indicative of premature atherosclerotic disease. In order to test this hypothesis, female control (NZW, n=20) and SLE (NZBWF1, n=20) mice were fed normal chow or a high fat diet supplemented with 0.5% cholate (HFD+cholate) for 14 weeks. Body weight and body composition were monitored by Echo MRI biweekly over the course of the study. At the conclusion of the study both carotid arteries and aortas were isolated from control and SLE mice. Carotid rings were suspended in organ chamber baths where endothelium‐dependent and endothelium‐independent relaxation were the concentration responses (10−8 to10−4 M) to acetylcholine (ACh) and sodium nitroprusside (SNP) were assessed in vessels pre‐contracted with the thromboxane mimetic U46619 (0.4 μg/mL). HFD+cholate did not alter maximal ACh (10−4 M) mediated relaxation (70.1±3.4% vs. 75.2±2.1% p=0.33) in control mice. However, SLE mice fed HFD+cholate had an impaired relaxation response to ACh (10−4 M) as compared to SLE mice fed normal chow (65.6±2.3% vs. 43.6±7.2%, p=0.02). SNP‐mediated relaxation was not different between the mice fed different diets in either control or SLE animals, indicating that the impaired ACh response in SLE mice is endothelial dependent. In order to examine the impact of HFD+cholate on atherosclerotic lesion formation, isolated aortas were subjected to en face staining using Sudan IV. Preliminary data suggest that control mice fed HFD+cholate did not develop atherosclerotic plaques, but SLE fed HFD+cholate showed evidence of plaques in the aortic arch. Taken together, these data suggest that the immune system dysfunction present in SLE may accelerate the progression of diet‐induced atherosclerosis.Support or Funding InformationE.B.T. was supported by an individual NIH National Research Service Award (F32HL137393). This work was supported by Veteran's Administration Merit award (BX002604‐01A2) to M.J.R. and NIH NHLBI awards PO1HL051971, P20GM104357 to UMMC‐Department of Physiology and Biophysics.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
A novel mouse model of kidney fibrosis induced by glomerulus‐specific overexpression of the full‐length of human transforming growth factor‐β1 gene
Authors: Takeshita Atsuro , Yasuma Taro , Hozumi Kenta , Nishihama Kota , D’ Alessandro‐Gabazza Corina N. , Totoki Toshiaki , Toda Masaaki , Yano Yutaka , Gabazza Esteban C 
Published: June 2021

Chronic renal disease is a common complication of several diseases including diabetes mellitus, hypertension and chronic glomerulonephritis. Approximately 10% of adults in developed countries suffer from chronic renal disease. Clinical progression of chronic renal disease leads to end‐stage renal disease that can be treated only with renal replacement therapy including dialysis and renal transplantation. There is currently no other therapeutic option for patients in terminal stages of the disease. The main reason of the scarce therapeutic strategies for this chronic and fatal disease is the lack of appropriate disease model to evaluate drug discovery. In the present study, we focused on the potent profibrotic activity of transforming growth factor‐β1 and its critical mechanistic role in glomerulosclerosis. We prepared and amplified a chimeric mouse podocin/human transforming growth factor‐β1 bacterial artificial chromosome construct, purified, linearized, separated by pulsed field gel electrophoresis and dialyzed before microinjection into fertilized eggs. We obtained several founders expressing the transgene as demonstrated by Southern blotting. As expected, the transgenic mice have increased plasma levels of human transforming growth factor‐β1, creatinine and blood urea nitrogen from 8‐weeks of age. The urine levels of fatty acid‐binding protein, a marker of kidney injury, and human transforming growth factor‐β1 were also significantly increased in the transgenic mice compared to wild type mice. Trichrome staining of the kidneys disclosed extensive deposition of extracellular matrix proteins in the transgenic mice compared to their wild type counterparts. In addition to highlighting the important role of transforming growth factor‐β1 in the pathogenesis of kidney fibrosis, the results of this study led to development of a novel mouse model of kidney fibrosis that may be useful for drug discovery.Support or Funding InformationI have no financial relationships to disclose.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Effects of Resistance Exercise on Kidney Antioxidant Enzymes of Rats Treated with Doxorubicin
Authors: Busekrus Raquel , Hydock David Scott , Tigner Allison , Kaufenberg Mikayla , Hook Sarah , Bredahl Eric 
Published: June 2021

The aim of this study was to investigate the effects of the anti‐cancer drug doxorubicin (DOX) and resistance exercise training on kidney antioxidant enzyme expression. Male rats were assigned to a resistance training (RR) or sedentary (SS) group for the first 10 weeks of the study. RR were housed in specialized resistance training cages, and SS were house in standard cages. After 10 weeks, animals received either weekly 3 mg/kg intraperitoneal injections of DOX over 4 weeks (12 mg/kg total, SSD, RRD) or an equivalent doses of 0.9% saline as control and continued with the activity treatments (SSS, RRS). Five days after the last DOX injection, kidneys were collected, and expression of the antioxidants catalase (CAT), superoxide dismutase 1 (SOD1), and glutathione peroxidase (GPx) was analyzed using Western blotting. Significant activity and drug main effects were observed for CAT expression (p=0.02 and p=0.0002, respectively) with SSD expressing significantly lower CAT than all other groups (p<0.05). With SOD1 expression, a significant activity effect (p=0.0088), drug effect (p<0.0001), and activity × drug interaction (p=0.0347) was observed. No significant main effects or interactions were observed for GPx, but there was a trend toward an activity effect (p=0.0706). Although more work is needed, the results of this study are promising, and we conclude that resistance training prior to and during DOX treatment may help to minimize renal damage by upregulating antioxidant enzyme expression.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The Effect of Fennel (Foeniculum vulgare) on the JAK/STAT Pathway and Intestinal Barrier Function
Authors: Rabalais John , Kozan Philip , Lu Tina , Durali Nassim , McGeough Matthew D. , Marchelletta Ron , Lee Jae Beom , Barrett Kim , Sivagnanam Mamata 
Published: June 2021

Foeniculum vulgare (F. vulgare), commonly known as fennel, is a flowering plant species in the family Apiaceae. It is believed to be one of the world's oldest medicinal herbs and has been used for its reported anti‐inflammatory and antipathogenic properties. Anethole, a major component of F. vulgare, has also been shown to inhibit tumor necrosis factor (TNF)‐induced activation of nuclear factor kappa B (NF‐kB) and interleukin‐1β in rats both of which are parts of wide ranging inflammatory pathways. F. vulgare has also been used as a complementary and alternative treatment for intestinal bowel disease (IBD) in some countries. To investigate this alternative treatment and F. vulgare's anti‐inflammatory properties further, the Janus Kinase/Signal Transducers and Activators of Transcription (JAK/STAT) pathway, which is known to be active in many forms of IBD, was selected to be interrogated by growing colonic (T84) monolayers in vitro with F. vulgare oil extract before being challenged with interferon‐gamma (IFN‐γ). A dextran sodium sulfate (DSS) murine model that was given F. vulgare extract was also used to model ulcerative colitis.Barrier studies of T84 monolayers showed pretreatments with F. vulgare oil extract significant protected transepithelial electrical resistance (TEER) as compared to monolayers which only received vehicle treatments prior to IFN‐γ challenge (Fig. 1A, P<0.01). IFN‐γ has been shown to significantly decrease TEER in cells.? Furthermore, tight junction protein‐1 (TJTP‐1) and occludin (OCLD), both important tight junction proteins, showed increased RNA expression in F. vulgare treated monolayers (Fig. 1B–C, P<0.05). Levels of STAT1 mRNA and total STAT1 protein were similar between IFN‐γ treatments, regardless of F. vulgare treatment (Fig. 2A, P>0.05). However, F. vulgare did inhibit phosphorylation of STAT1, showing decreasing amounts of pSTAT1 with increasing amounts of F. vulgare in T84 monolayers (Fig. 2B, P<0.05). In the DSS‐murine studies, mice given F. vulgare treatments showed marked decreases in ulcer indices as compared to mice only given DSS (Fig. 3B, P<0.05). mRNA transcripts of STAT1 showed decreases in F. vulgare treated mice when compared to mice only given DSS (Data not shown). Both phosphorylated STAT1 and total STAT1 levels were decreased in F. vulgare treated mice as compared to mice only given DSS (Fig. 4, P<0.05). The results of the in vitro and in vivo experiments demonstrate F. vulgare's protective effects on gastrointestinal barrier integrity and overall macroscopic structure in the colon. We propose that F. vulgare inhibits phosphorylation of STAT1 in vitro and inhibits both phosphorylation and transcription of STAT1 in vivo.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Engineered bacterial Tight Junctions: a high‐throughput method to identify absorption enhancers
Authors: Rollings Jay , Worthington Tyler , Mizrachi Dario 
Published: June 2021

Tight Junctions are the master regulators of the paracellular space and the gatekeepers of the blood‐tissue barriers. Claudins are the membrane proteins responsible for cell‐cell contacts at the Tight Junctions. Absorption enhancers (AE) are molecules that disrupt the paracellular space at the Tight Junction level, allowing for increased transport of material between cells. Thus, greatly enhancing the translational potential for drug delivery and even for enabling new drug discovery. Currently, no AE have been identified for clinical use because the current setting of studying Tight Junctions involves mammalian cell monolayers in a very low throughput setting. We engineered a claudin protein which can be expressed in the outer membrane of E. coli. Thus, the E. coli are endowed with Tight Junction‐like structures driving cell to cell interactions. This new approach provides us with a high‐throughput method to interrogate investigate large libraries of compounds to identify AE. Our results indicate that known AE affect both mammalian and E. coli Tight Junctions in similar fashion. Results from the high‐throughput E. coli system can be translated to mammalian cells and result in candidates for translational solutions and new drug design.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Effect of Univestin (Scutellaria baicalensis root & Acacia catechu heartwood) on Post‐Exercise Muscle Soreness and Range of Motion in Healthy Adults
Authors: Talbott Shawn M , Talbott Julie A , Hantla Don 
Published: June 2021

IntroductionIntense exercise is known to increase post‐exercise pain and result in delayed‐onset muscle soreness (DOMS) lasting for several days. Muscle soreness and soft tissue pain is a frequent complaint among recreational exercisers and a significant obstacle to continued participation in regular physical activity.ObjectiveOur study examined the effects of an herbal dietary supplement (Univestin; combination of Scutellaria baicalensis root & Acacia catechu heartwood) versus a look‐alike placebo on subjective pain and range of motion (ROM) following intense exercise.Subjects & MethodsTwenty‐three (N=23) healthy men and women were recruited to participate in an intense 60‐minute “boot camp style” resistance training workout designed to induce DOMS across all major muscle groups (quadriceps, hamstrings, gluteals/hips, shoulders, biceps, triceps). Subjects were randomly divided in double‐blind fashion to receive either the supplement (Univestin) at 250 mg b.i.d. (N=12) or placebo (N=11) for 1‐week post‐exercise. We measured range of motion (ROM), joint pain (WOMAC; Western Ontario & McMaster Universities Osteoarthritis Index), and muscle pain/stiffness (VAS; visual analog score) daily during the 1‐week post‐exercise period.ResultsSubjective evaluation of pain/stiffness (VAS) was noticeably lower across several muscle groups (calves, gluteals/hips, biceps, triceps) at day‐1 and significantly lower (p<0.05) by the 2nd day post‐exercise in the Univestin group compared to Placebo. ROM scores were significantly higher across both shoulder and hip movements (flexion/extension) at all time points from day‐1 to day‐6 post‐exercise in Univestin compared to Placebo (p<0.05). Measures of joint pain (WOMAC) were also lower in Univestin versus Placebo at some, but not all, timepoints.ConclusionUnivestin has previously been reported to reduce the pain and stiffness associated with osteoarthritis (1–3). These clinical results further demonstrate Univestin's effectiveness to reduce post‐exercise muscle pain and improve range of motion in a population of healthy non‐arthritic adults. Therefore, Univestin may be viewed as an effective dietary supplement to facilitate healthy pain‐free participation in regular physical activity.Support or Funding InformationFunding provided by UnigenThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Biological Metabolite and Resveratrol Interaction in Cholesterol Diet Fed Rabbits
Authors: Jimoh Abdulazeez , Olusegun Ayorinde Joseph , Tanko Yusuf , Abubakar Ahmed , Aliyu Mohammed 
Published: June 2021

Serum adiponectin concentration is inversely associated with leptin and insulin concentration. There is little paucity of information in the literature on the adipocytes levels and regulations by resveratrol in cholesterol diet‐fed rabbit. Thirty rabbits were randomly divided into six groups, each of five animals: Group 1 = control, Group 2 = cholesterol diet (CD) only, Group 3 = resveratrol 200 mg/kg (R200), Group 4 = resveratrol 400 mg/kg (R400), Group 5 = CD + R200 and group 6 = CD + R400. The preparations were administered for eight weeks of experimental protocol. weight and blood glucose level were measured using digital weighing balance and glucometer on week zero and the eighth week of the experiment. At the end of the study period, the rabbits were placed under light anesthesia (ketamine) to remain unconscious. blood sample of about 3ml was drawn via cardiac puncture for serum extraction which were evaluated for serum concentration of metabolites assays (adiponectin, leptin and insulin). Blood glucose level and body weight were significantly higher in CD group compared to groups that received CD + resveratrol supplement and resveratrol only. Serum adiponectin showed significant (P < 0.05) increased in CD + resveratrol groups, compared to CD group only. Leptin and insulin significantly shows (P < 0.05) decreased in in CD groups co‐administered with resveratrol and resveratrol groups only compared to CD group only.in conclusion, the decrease in body weight and blood glucose level demonstrated the antidiabetic effect of resveratrol and increase in adiponectin level, decrease in leptin and insulin level following resveratrol supplement elucidated the therapeutic potential of resveratrol, despite cholesterol diet consumptions.Support or Funding InformationTETfUND (Tertiary Education Trust Fund Nigeria) and Ahmadu Bello University, Zaria, Kaduna State, NigeriaThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Fenofibrate Prevents Weight Gain in DIO Mice Independent of Subcutaneous White Adipose Tissue Browning
Authors: Rodrigues Alice Cristina , Rocha Karina Cunha 
Published: June 2021

Activation of peroxisome proliferator activated receptor alpha (PPARα) affects energy metabolism in adipocytes. Our group and others have shown fenofibrate, a PPARα agonist, increases energy expenditure and prevents weight gain in diet‐induced obese mice. The aim of this study is to evaluate if fenofibrate‐induced weight loss is a consequence of subcutaneous white adipose tissue browning. Male C57BL/6 mice at 8 weeks' old (n ± 40; CEUA 165/2011) were randomly assigned to receive a control (CD) or a high‐fat diet (HFD) for 6 weeks. After that, they were subdivided into four groups: C group (fed with CD, untreated), CF group (fed with CD and treated with fenofibrate), H group (fed with HFD, untreated) and HF group (fed with HFD and treated with fenofibrate). Fenofibrate (50 mg/Kg/day) was administered daily by oral gavage for 2 weeks. After 48h of the last dose, they were euthanized. Expression of mRNAs (Ucp1, Elovl3 and Eva‐1) in inguinal adipose tissue were measured by Real‐time PCR assay. Mice fed with HFD showed augment of body weight gain, visceral fat depots weights, fasting leptin and insulin serum levels and reduced constant of glucose disappearance (Kitt). Without changes in food intake, fenofibrate treatment attenuated the weight gain in both CF and HF groups, contributing to reduce the adipose tissue storage, and restored insulin and leptin levels when compared to C group. Kitt was not different between HF and H groups. Expression of Ucp1, Elovl3 and Eva‐1 were down regulated in obese mice and fenofibrate had no effect on their expression. On the other hand, in control mice, fenofibrate increased Eva‐1 expression, a gene characteristic of classical murine brown fat. In conclusion, fenofibrate prevents weight gain in obese mice by a mechanism that seems not to involve subcutaneous white adipose tissue browning.Support or Funding InformationFAPESP and CAPESThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
SLN overexpression upregulates mitochondrial dynamics and promotes oxidative metabolism during caloric restriction.
Authors: Periasamy Muthu , dos Reis Felipe Gomes 
Published: June 2021

Obesity results from increased caloric intake, physical inactivity and is a major contributor to type 2 diabetes (T2D). Exercise and caloric restriction (CR) are the most effective interventions to prevent obesity, T2D and sarcopenia. By increasing fatty acid oxidation (FAO), CR promotes insulin sensitivity and improves mitochondrial function. Our laboratory has identified Sarcolipin (SLN) as an important player in muscle thermogenesis. SLN‐binding to SERCA promotes uncoupling of Ca2+ transport, causing futile cycling of the SERCA pump, increasing energy expenditure. SLN overexpression in glycolytic muscle leads to increased mitochondrial biogenesis and FAO, resembling an oxidative phenotype. Therefore, we sought to determine if SLN overexpression (1) promotes resistance to fatigue and increased exercise performance and (2) improves the beneficial effects of CR in skeletal muscle mitochondrial metabolism. Wild type (WT), Sarcolipin knockout (SLN−/−) and Sarcolipin overexpression (SLNOE) mice were submitted to 8 weeks of exercise training at 60% of maximal effort capacity. After exercise, oxygen consumption, maximal force and resistance to fatigue were measured in isolated muscles. Electronic transport chain (ETC) and oxidative phosphorylation (OXPHOS) related proteins were analyzed in muscle and adipose tissue. Exercise‐induced increase in ETC proteins of white adipose tissue was blunted in SLN−/− mice. Our results show that SLNOE are resistant to fatigue and show better functional recovery as compared with WT and SLN−/−. Oxygen consumption is also increased in tibialis anterior after exercise in SLNOE, indicating that SLN overexpression in glycolytic muscle improves FAO and promotes endurance capacity. To induce CR, 3 month‐old male WT, SLN−/− and SLNOE mice were submitted to 8 weeks of 40% CR protocol, and body weight was measured weekly. Glucose tolerance test and insulin sensitivity measurements showed that SLNOE improved CR‐induced insulin sensitivity and glucose tolerance. Western blot analysis revealed that CR‐induced increase in ETC proteins (Complex I to V) and mitochondrial content (Tfam) is SLN‐dependent. Secondly, SLN increases mitochondrial fusion (Mfn1 and Opa1) and fission (Drp1) proteins and, as expected, CR increased markers of autophagy (LC3‐ II). Our data indicates that SLN plays an important role in metabolic adaptations in muscle by modulating mitochondrial dynamics and promoting oxidative metabolism. We propose that SLN can contribute to CR induced metabolic benefits in muscle.Support or Funding InformationNIDDK ‐R01 DK098240This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.