bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of the Effects of Cryotherapy and Thermotherapy on Permeability After Skeletal Muscle Injury
Authors: Gasser Brittany , Tusavitz Sabrina , Carpenter April 
Published: June 2021

Skeletal muscle injuries are common in active individuals. The inflammatory process is a vital component of muscle healing beginning with enhanced permeability. As blood vessels dilate, inflammatory promoting proteins and white blood cells enter the damaged area to eliminate debris and initiate regeneration. The application of controlled temperature on the injured muscle remains the most common treatment. However, there is conflicting evidence on the advantages of cryotherapy, and there is a lack of evidence on benefits of thermotherapy. Therefore the purpose of our study was to compare the effects of cryotherapy and thermotherapy on muscle vascular permeability in both male and female mice. Barium chloride (BaCl2) was injected into the right tibialis anterior (TA) to cause a chemical injury and sodium chloride (NaCl) was injected into the left TA as a control. Therapy was started immediately after injury. The control group was anesthetized, the thermotherapy group received heat treatment (41°C) while anesthetized, and the cryotherapy group received cold therapy (10°C) while anesthetized, for 20 mins every 3 hours, during 2 consecutive 12 hr wake cycles. Evans Blue (EB) dye was injected through the lateral tail vein to assess vascular permeability in the TA muscles. There was no significant difference in permeability between the NaCl injected muscles regardless of treatment. Permeability 36 hours post‐injection was significantly elevated in the BaCl2 injected TA muscles in all groups. Cryotherapy significantly reduced permeability in the BaCl2 injured muscles as compared to thermotherapy (cryotherapy: 4.78±2.68 vs. thermotherapy: 11.1±2.32 ngEB/mgTA). Our data suggests that cryotherapy limits permeability 36 hrs post‐skeletal muscle injury. New data suggests inflammation is necessary for efficient muscle healing. Therefore new treatments for muscle injury should be considered.Support or Funding InformationUrsinus College Student Research FundingThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
MG29 Interacts with Bin‐1 to Maintain T‐Tubule Structure in Skeletal Muscle Physiology and Regeneration
Authors: Yi Frank , Zhou Xinyu , Gumpper Kristyn , Zhu Hua 
Published: June 2021

Mitsugumin 29 (MG29), a member of the synaptophysin‐like family proteins, is a transmembrane protein primarily expressed in the t‐tubule membranes of skeletal muscle. In the current study we have found that t‐tubules in skeletal muscle of mg29−/− have defective morphology, indicating importance of MG29 in maintenance of muscle structure and function. To elucidate the role of MG29 in muscle physiology, we performed two‐color STORM super‐resolution imaging analysis confirmed co‐localization of MG29 and Bin‐1 on t‐tubules of skeletal muscle. We also performed co‐immunoprecipitation and found that MG29 can bind to Bin‐1, another t‐tubular protein. Recombinant MG29 protein domain fragments tagged with GST were expressed and Bin‐1 was found to bind to the cytosolic domains of MG29. Furthermore, organized distribution of Bin‐1 is severely disrupted in mg29−/− muscle. To test the function of MG29 in muscle regeneration, we injured gastrocnemius muscle with cardiotoxin (CTX) and tracked muscle repair and regeneration. Western blot showed that following CTX injury, MG29 protein levels were transiently reduced from day 1 to day 3, followed by recovery associated with muscle regeneration by day 5. Protein level of Bin‐1 in wild type muscle was also reduced upon CTX‐injury and increased during the recovery process. Compared with wild type muscle, the mg29−/− muscle displayed delayed regeneration and increased fibrosis following CTX‐induced injury. Together our data suggest that functional interaction between MG29 and Bin‐1 contribute to maintenance and formation of t‐tubule network while playing a role in muscle regeneration and regeneration. Targeting this MG29‐Bin‐1 interaction might provide a potential effective approach for treatment of muscle diseasesSupport or Funding InformationThis work was supported by grants from the National Institutes of Health (NIH) (AR067766 and HL124122)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Whole Body Hyperthermia Ameliorates Inflammation via Regulating Pro‐inflammatory but not Anti‐inflammatory Macrophages in Tenotomized Rat Skeletal Muscle
Authors: Hirunsai Muthita , Srikuea Ratchakrit 
Published: June 2021

Following disuse condition, macrophages play significant role in inflammatory responses during muscle degeneration and repairing processes. Pro‐inflammatory (M1 phenotype) macrophage becomes classically activated during an initial phase of muscle degeneration. Contrariwise, anti‐inflammatory (M2 phenotype) macrophage abrogates inflammation by deactivating M1 macrophage and promotes muscle growth in repairing stage. Previously, we demonstrated that heat treatment alleviates the loss of muscle mass via enhancing intramuscular capillarization and remodeling extracellular matrix in disuse muscle. Of these, the effect of heat stress on inflammatory responses in tenotomy‐induced atrophy is currently unknown. In this study, the effect of hyperthermia on M1 and M2 macrophage populations as well as the responses of inflammatory cytokine protein expression in the soleus muscle following Achilles tendon transection (tenotomy) were examined. Male Wistar rats were designed into sedentary control (CON), tenotomy without heat treatment (TEN), and tenotomy plus heat treatment (TEN+HEAT) groups. Whole body hyperthermia was maintained in TEN+HEAT group with animal core body temperature at 40.5–41.5°C, 30 min for 7 days. After 8 days of tenotomy, soleus muscle demonstrated a reduction in fiber size and tremendous infiltration of inflammatory macrophages. These occurrences coincided with an increase in pro‐inflammatory cytokine, particularly tumor necrosis factor‐alpha (TNF‐α). Whilst tenotomy had no effect on interleukin‐10 (IL‐10) which is an anti‐inflammatory cytokine. Interestingly, whole body hyperthermia diminished accumulation of M1 macrophages and associated with reduction of TNF‐α protein expression in tenotomized muscle. Nevertheless, heat stress affected neither M2 macrophage phenotype invasion nor IL‐10 protein level following tenotomy. Collectively, heat stress relieved tenotomy‐induced inflammatory response, partly by inhibiting M1 macrophage invasion. Our findings provide a foundation for therapeutic strategy of heat stress on fiber inflammation during skeletal muscle atrophy.Support or Funding InformationThe research was supported by the grant from Srinakharinwirot University (to MH).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Renal Dysfunction Exacerbates Ischemic Muscle Injury in Mice Subjected to Hindlimb Ischemia
Authors: Berru Fabian N. , Gray Sarah E. , Thome Trace , Le Dennis , Omalley Kerri A. , Berceli Scott A. , Scali Salvatore T. , Ryan Terence E. 
Published: June 2021

Patients with critical limb ischemia (CLI) have multiple concomitant comorbidities which are associated with poorer overall health outcomes. CLI patients with impaired kidney function and/or diabetes are at greater risk for limb amputation and death. While the negative impacts of renal dysfunction and diabetes on CLI outcomes are known clinically, the underlying biologic mechanism(s) responsible are poorly understood. Thus, we sought to evaluate the impact of impaired renal function and diabetes on the skeletal muscle pathology in mice following unilateral hindlimb ischemia (HLI). Renal dysfunction (RD) was induced by dietary administration of adenine which causes renal tubular injury, while diabetes was induced by streptozocin injection. HLI was induced by ligation and excision of the femoral artery, while the contralateral hindlimb was utilized as a control (no surgery). Three groups (n = 15; 5 per group) of C57BL/6J mice were analyzed: control, RD, and RD+ diabetes. Skeletal muscle ischemic injury was assessed using histological measurements of myofiber centralized nuclei, myofiber cross‐sectional area, ischemic lesion areas, and vascular density. High‐resolution O2 consumption was used to examine mitochondrial function in permeablized myofibers. Mice with RD, regardless of diabetes, exhibited greater ischemic lesions within the tibialis anterior muscle (Con = 2.53 ± 0.51% vs. RD = 60.554 ± 24.15% vs. RD+STZ = 79.99 ± 19.99%; P < 0.0001) despite similar capillary density (Con = 466.36 ± 44.98 vs. RD = 455.20 ± 79.55 vs. RD+STZ = 578.20 ± 87.16 capillaries/field; P = 0.9011). Mice with RD exhibited a ~45% decrease in mitochondrial respiratory capacity across numerous substrates, whereas control mice had normal respiration in the ischemic limb muscle seven days post‐HLI. These observations demonstrate that impaired kidney function exacerbates ischemic muscle injury in mice. Future studies are needed to uncover the molecular mechanisms by which RD negatively impacts skeletal muscle.Support or Funding InformationSupported by AHA Grant 18CDA34110044 to TER.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Functional Role of microRNAs in Patient‐Derived Xenograft Models of Human Cholangiocarcinoma
Authors: Wu Nan , McDaniel Kelly , Glaser Shannon , Celinski Scott , Dhruv Harshil , Alpini Gianfranco , Meng Fanyin 
Published: June 2021

BACKGROUND & AIMSPatient‐derived xenograft (PDX) models are now being widely used in cancer research including liver and biliary carcinogenesis, and have the potential to feedback and improve the therapeutic effects in cancer patients. MicroRNAs (miRNAs) are highly conserved 19–25 nucleotide non‐coding small RNAs which are primarily involved in gene silencing. Our aim was to characterize the functional roles of microRNA regulated protein translocations in patient‐derived cholangiocarcinoma xenograft tumors.METHODSmiRNA expression in human cholangiocarcinoma cancer tissues, patient‐derived cholangiocarcinoma xenograft tissues, human extrahepatic cholangiocarcinoma cancer stem cells (GB‐CSCs)/Mz‐ChA‐1 extrahepatic cholangiocarcinoma cancer cells and their derived xenograft tumor tissues, as well as H69 non‐malignant cholangiocytes was assessed using a hybridization based microarray and was further evaluated by Taqman real‐time PCR analysis. Promoter methylation, matrix metalloproteinase (MMP) 1, 2, 3 and 9 mRNA expression was quantitated by real‐time PCR and western blot analysis.RESULTSWe identified miR‐200 family including miR‐200a, miR‐200b and miR‐200c that are differentially expressed in doxorubicin‐enriched cell fractions in a patient derived mouse xenograft tumor model of extrahepatic cholangiocarcinoma. Members of the miR‐200 family were notably more silenced in GB‐CSCs compared with their parental extrahepatic cholangiocarcinoma cancer cells (GBCs) and Mz‐ChA‐1 cells. Expression of miR‐200 family microRNAs and transmembrane protein MMP‐2 and MMP‐9 were substantially enhanced concomitant with GBCs differentiation and loss of self‐renewal, whereas forced expression of a polycistron construct encoding miR‐200 miRNAs significantly decreased chemoresistance to doxorubicin. Methylation‐specific PCR detected that miR‐200b and miR‐200c promoter was hypermethylated in GB‐CSCs, GBCs as well as Mz‐ChA‐1 cells. Cell migration and invasion were significantly decreased by miR‐200 precursor introduction in GB‐CSCs and Mz‐ChA‐1 cells. Bioinformatics and dual‐luciferase reporter assays identified ZEB1 and ZEB2 as the direct targets of miR‐200 family.CONCLUSIONOur results define a novel oncogenic regulatory mechanism of specific microRNA group in patient derived cholangiocarcinoma xenograft models and suggesting that miR‐200 cluster may be the molecular targets for eradication of human cholangiocarcinoma.Support or Funding InformationTGEN grant from Translational Genomics Research InstituteThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The Art of Border Crossings: Integrative Multidisciplinarity in the Natural Sciences and the All Atom Model of a Native HIV Capsid
Authors: Gronenborn Angela 
Published: June 2021

Those of us engaged in active experimental research careers rarely have the opportunity to step back from the lab bench or the computer to reflect on how scientific practice has changed, what kinds of interactions have proved effective, and how to begin to articulate the features of successful research. In the field of Structural Biology, which is in practice deeply inter‐ and multi‐disciplinary, research at the interfaces of traditional disciplines, such as Biology, Chemistry, and Physics is essential for addressing the most important problems. If future progress in the natural sciences depends on escaping from the restraints of narrowly disciplinary language and frameworks, as I believe it is, then we will need new approaches and language to negotiate these boundaries and teach the ‘art of border crossing’ to young scientists. In my talk I will present an example of research carried out by a team of scientists that hail from different fields. Using solution NMR, MAS solid state NMR, crystallography, cryoEM and large‐scale MD simulation permitted the construction of all‐atom models for the hexamer‐of‐hexamer and pentamer‐of‐hexamer elements that make up the HIV‐1 capsid core, which, in combination with cryo‐ET, allowed us to derive a realistic all‐atom model for the entire capsid.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Personalizing Food to the Gut Microbiome
Authors: David Lawrence 
Published: June 2021

Dietary polysaccharides from plants nourish human gut bacterial communities (microbiota). These carbohydrates promote the growth of resident microbes that resist pathogens, metabolize drugs, and train the immune system. Short‐chain fatty acids, which are end products of microbial polysaccharide fermentation, are also crucial metabolic precursors and energy sources for human colon cells. Yet, despite growing awareness for the importance of polysaccharides on gut bacterial growth and metabolism, optimal strategies for consuming these carbohydrates have lagged. Multiple sources of dietary carbohydrates (prebiotics) exist and each has varying effects on gut bacterial species. Moreover, gut microbial communities vary widely between people and even within individuals over time. Here, we describe our efforts to understand how prebiotic treatments should account for inter‐individual differences in gut microbiota composition. These efforts rely on experimental tools including high‐throughput bacterial culture assays and artificial gut systems. Using these systems, we find evidence for prebiotic‐ and individual‐specific components of gut microbiota responses to prebiotic therapy. We also observe changing prebiotic responses within individual gut microbiota over time. Lastly, our experiments suggest the potential for developing diagnostics to predict individual prebiotic response.Support or Funding InformationLAD acknowledges support from the Global Probiotics Council, a Searle Scholars Award, the Hartwell Foundation, an Alfred P. Sloan Research Fellowship, the Translational Research Institute through Cooperative Agreement NNX16AO69A, the Damon Runyon Cancer Research Foundation, the Hartwell Foundation, and the NIH (1R01DK116187‐01, P30 DK034987).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Cell line xenograft growth in the B6;129‐Rag2tm1FwaIL2rgtm1Rsky/DwlHsd (R2G2) mouse model
Authors: Naden Jamie 
Published: June 2021

Immunodeficient mouse models are helping to advance the field of oncology. A new model on the market, the B6;129‐Rag2tm1FwaIL2rgtm1Rsky/DwlHsd (R2G2) knockout mouse, lacks responsiveness to common gamma chain cytokines, including IL‐2, IL‐4, IL‐7, IL‐9 and IL‐15. In addition, this model exhibits defects in lymphoid development and so lacks mature lymphocytes of the B, T, and natural killer (NK) cell lineages. Herein we describe growth and take rate of a few tumor cell line xenografts in the R2G2 immunodeficient mouse model. The cell line xenografts studied include multiple myeloma, pancreatic, Burkitt's lymphoma, ovarian, and breast cancer. Multiple myeloma (MM1.S cells) were inject via the tail vein at 50 × 104 cells per mouse. IVIS imaging was used to measure tumor burden of luciferase transfected cells. The pancreatic cancer (BxPC‐3 cells) was injected subcutaneously at 1 × 106 and tumor volume was measured weekly. Burkitt's lymphoma (RAJI) cells, ovarian (A2780) cancer cells, and breast (T47D, MDA‐MB‐231, and MCF‐7) cancer cells were implanted subcutaneously at 1 × 106 cells in both flanks of five mice each. Tumor volume and body weight was measured twice weekly for five weeks. These data provide evidence that the R2G2 mouse model is a valuable tool for oncology programs including cell line tumor models research, with high take rates and quick growth of allogeneic models.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
A Rare Case of an 83‐Year‐Old Male Transgender: An Anatomical and Genetic Study
Authors: Polcaro Lauren , Lawson Craig , Tan Yun , Tersigni‐Tarrant MariaTeresa , Frolov Andrey , Martin John 
Published: June 2021

BackgroundTransgender is a broad term which describes an individual whose gender self‐identification is different from the assigned sex at birth. When the latter becomes overwhelming and causes a significant psychological impact, the term gender dysphoria is used thereby presenting itself as an extreme case of transgenderism. The individuals with gender dysphoria often seek a medical intervention, surgical or therapeutic, to correct the existing discordance between their gender self‐identification and physical appearance.ResultsIn the current report, we describe a rare case of an 83‐year‐old male who self‐identified as a female by legally changing his first and middle names to female ones and whose death certificate states his sex as a female. Yet, an initial visual examination of the body revealed an absence of penis with a large scrotum and atrophied testes. It was an opinion of an experienced urologic surgeon that this individual most likely underwent a penectomy with perineal urethrostomy. Dissection of the pelvic cavity and perineum revealed normal male anatomy with testes, spermatic cords, ductus deferens, seminal vesicles, and prostate intact. Histological analysis of the testes and prostate revealed striking anomalies within the tissues. The seminiferous tubules had an abnormal epithelium with no germ, Sertoli, or Leydig cells present. Histological analysis of the prostate pointed to its non‐functional state whereas the gross tissue structure was more consistent with a prostate of a young adult. Yet amyloid deposits were found in the vasculature in the testes and prostate, which would support sepsis being the official cause of death. In order to gain additional insights into the current case, a genetic screen was performed by exome sequencing of DNA extracted from the embalmed cadaveric tissue using the Next Generation Sequencing (NGS) Illumina platformConclusionThe available personal information pertinent to the examined body identifies this individual as a transgender. The results of the genetic screen will help to define this case further by establishing a probable cause for penectomy and choosing between two most obvious alternatives; an elective surgery for the correction of gender discordance or a surgery associated with penile or urethral cancer. Yet, the genetic screen could also indicate an impaired hormonal production and/or signaling that would explain the observed testicular and prostatic atrophies. If not, the latter could be caused by a chemical castration. Overall, all those data will help to assess the severity of the current case of transgenderism and its possible progression to gender dysphoria.Support or Funding InformationCenter for Anatomical Science and Education, Department of Surgery, Saint Louis University School of MedicineThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Effect of Anti‐hypertensive Treatment Lisinopril on Anxiety‐like Behavior in Adult Hypertensive Dahl Salt‐Sensitive Rats
Authors: Fenner Rachel Claire , Grigorova Yulia , McDevitt Ross , Petrashevskaya Natalia , Wei Wen , Lakatta Edward , Fedorova Olga 
Published: June 2021

BackgroundIndependent of a high salt intake, Dahl Salt‐Sensitive (DSS) rats demonstrate an age‐associated increase in blood pressure (BP) accompanied by cognitive decline. We sought to explore the effect of anti‐hypertensive treatment, Lisinopril, which lowers tissue angiotensin II levels, on BP and behavior in adult DSS rats. We hypothesized, that Lisinopril, in addition to BP decrease, will affect the cognitive status of adult DSS.MethodsSixteen 6‐month‐old male DSS rats were kept on normal salt diet for the duration of the study; eight of them were continuously treated with 250 mg/L Lisinopril administered through their water for 2 months (15 mg/kg/day), and eight DSS rats remained on regular water as a control. Systolic BP (SBP) was measured in conscious male DSS rats via tail‐cuff plethysmography, and open field test (OFT) was performed to assess locomotor and anxiety‐like behavior at baseline prior to treatment and repeated 2 months after treatment began. Statistical regression analyses were performed using Prizm 7: 1‐way and 2‐way ANOVA, T‐test when applicable. The data are presented as mean ± standard deviation.ResultsPrior to treatment, all DSS rats displayed hypertension and BP elevation with age (SBP: 170 ± 11 vs. 142 ± 5 mmHg, 6‐mo vs. 3‐mo, n=16; P<0.01). After 2 months, control untreated animals showed no difference in SBP and were hypertensive (170 ± 15 vs. 168 ± 13 mmHg, 8‐mo vs. 6‐mo, n=8; n/s). Rats treated with Lisinopril for 2 months showed a dramatically decreased SBP compared to their baseline prior to treatment (119 ± 9 vs. 171 ± 11 mmHg, P<0.0001, n=8; Fig. 1), verifying the efficacy of the drug. In OFT, treatment with Lisinopril increased exploration of the center of the field compared to the control group (160 ± 45 vs. 91 ± 55 % of distance traveled in center to baseline, p=0.0166, n=8/group; Fig. 2) without affecting total distance traveled, indicating a reduction in anxiety‐like behavior. Furthermore, there was a significant negative correlation between SBP and increased activity in the center of the field (Pearson R=−0.58, R2=0.34, P=0.018; Fig. 3), suggesting anxiolytic effects of BP lowering medication.ConclusionLowering of BP is associated with reduced anxiety‐like behavior in DSS, which indicate the connection of cardiovascular disorder and cognitive function in adult hypertensive DSS. Whether Lisinopril has an additional direct effect on brain functions in DSS rats will be further studied.Support or Funding InformationSupported by NIH/NIA Intramural Research ProgramThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.