bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of contraction mode in determining exercise tolerance, torque-duration relationship, and neuromuscular fatigue
Authors: Ducrocq Guillaume , Al-Assad Simon , Nabil Kouzkouz , Hureau Thomas 
Published: May 2023

Purpose: Critical torque (CT) and work done above it (Wʹ) are key predictors of exercise performance associated with neuromuscular fatigue. The aim of the present study was to understand the role of the metabolic cost of exercise in determining exercise tolerance, CT and Wʹ and the mechanisms of neuromuscular fatigue. Methods: Twelve subjects performed four knee extension time-trials (6, 8, 10, and 12-minutes) using eccentric, isometric, or concentric contractions (3s-on/2s-off at 90° or 30°/s) to modulate the metabolic cost of exercise. Exercise performance was quantified by total impulse and mean torque. CT and Wʹ were determined using the linear relationship between total impulse and contraction time. Cardiometabolic, neuromuscular, and ventilatory responses were quantified. Neuromuscular function was evaluated by maximal voluntary contraction, resting potentiated single/doublet electrical stimulations, and superimposed single electrical stimulation to quantify neuromuscular, peripheral, and central fatigue, respectively. Results: Compared to isometric exercise, total impulse (+36±21%; P<0.001), CT (+27±30%; P<0.001), and Wʹ (+67±99%; P<0.001) were increased during eccentric exercise whereas total impulse (-25±7%; P<0.001), critical torque (-26±15%; P<0.001) and Wʹ (-18±19%; P<0.001) were reduced in concentric exercise. Conversely, the metabolic response and the degree of peripheral fatigue were reduced during eccentric exercise whereas they were increased during concentric exercise. CT was negatively associated with oxygen consumption gain ( R2=0.636; P<0.001) and Wʹ was negatively associated with rates of neuromuscular and peripheral fatigue indices ( R2=[0.252-0.880]; P<0.001). Conclusion: The contraction mode influenced both CT and Wʹ, and consequently exercise tolerance, indicating that the metabolic cost of contraction played a key role. This work was supported by the University of Strasbourg Initiative of Excellence (2021-022-10 and ANR-10-IDEX-0002-02) This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Prolonged therapeutic effects of exosomes from light treated-adipose-derived stem cells on obesity-associated insulin resistance
Authors: Wu Jianbo , Wu Jiaqi 
Published: May 2023

Background: Obesity induces adipose tissue chronic inflammation resulting in insulin resistance and metabolic disorders. With light activation, we recently showed that in situ transplantation of photoactivated adipose-derived stem cells (ASCs) improves glucose metabolism by suppressing adipose tissue macrophages in obese mice. Still, the mechanisms have not been thoroughly investigated. Methods: Cultured ASCs were subjected to light treatment, and exosomes (Exos) were subsequently harvested and injected intraperitoneally into HFD mice. High-throughput miRNA sequencing was performed to detect the miRNA profiles of light-activated ASCs-Exos. The roles of miRNA and target gene were predicted and analyzed in vitro or in vivo by dual-luciferase reporter gene assay, specific miRNA mimic, miRNA inhibitor, and siRNA. Results: We showed that light-activated ASCs produce miRNA-containing exosomes (Exos), which significantly prolonged therapeutic effects on the improvement of obesity-associated insulin tolerance when injected intraperitoneally into obese mice. Mechanistically, light-activated ASCs-Exos shift M1 macrophages toward the M2 via miR-3572-5p–mediated targeting of ELVAL1 in vitro and in vivo. Moreover, miR-3572-5p inhibitor delivery significantly modulated insulin sensitivity and macrophage phenotype. Conclusions: These data suggest that light activation is a simple and effective method for generating the functionality of ASCs-Exos, and miR-3572-5p could be a new therapeutic target of adipose tissue inflammation for insulin resistance. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Inhibition of EB3 promotes acute lung injury resolution by promoting the regenerative FOXM1 pathway in endothelial cells
Authors: Chan Wan Ching , Kwok Man Long , Qu Xinyan , Zhao Shuangping , Le Jonathan , Komarova Yulia 
Published: May 2023

Acute respiratory distress syndrome (ARDS) is the acute onset of non-cardiogenic pulmonary edema, hypoxemia, and respiratory failure. ARDS is frequently caused by bacterial and viral lung infections including the recent SARS-CoV-2. Development of therapeutic approaches to combat ARDS have become an urgent unmet medical need. We address this medical problem by developing a pharmacological treatment for pulmonary vascular leakage, a culprit of alveolar damage and lung inflammation. Our novel therapeutic target is the microtubule accessory factor End Binding protein 3 (EB3), which contributes to pulmonary vascular leakage by amplifying pathological calcium signaling in endothelial cells. Using a structure-activity-relationship approach by Nuclear Magnetic Resonance, we have identified a drug candidate Vascular Therapeutics (VT)-109, an allosteric EB3 inhibitor with optimized physicochemical and biochemical properties. The VT-109 shows marked therapeutic benefits in treating lung injury and inflammation in various models of ARDS including high-volume mechanical ventilation, polymicrobial and SARS-CoV-2 infections. Transcriptome analysis of lung endothelial cells in mice challenged with endotoxin shows that VT-109 upregulates FOXM1 target genes suggesting that the treatment not only mitigates vascular injury but also promotes endothelial cell regeneration by activating the FOXM1 pathway. Our work demonstrates that VT-109 is a promising drug candidate for future clinical studies. Funding for this work is provided by the Congressionally Directed Medical Research Programs through the Peer Reviewed Medical Research Program (PRMRP) under award No. W81XWH-21-1-0639. Opinions, interpretations, conclusions, and recommendations are those of the author and are not necessarily endorsed by the Department of Defense. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
GCPII Inhibition Delays Age-related Loss of Muscle Mass and Function in Mice
Authors: Su Yu 
Published: May 2023

Sarcopenia, the age-related loss of skeletal muscle mass and function, is a significant problem that reduces the quality of life in the elderly. Despite the growing prevalence of sarcopenia, there is still a lack of effective therapies for this disease. Recent research has focused on the role of the enzyme glutamate carboxypeptidase II (GCPII) in regulating muscle function and neuromuscular junction (NMJ) integrity. We have previously shown that inhibition of GCPII with the potent inhibitor 2-(Phosphonomethyl)-pentanedioic acid (2-PMPA) can significantly delay muscle function loss and NMJ denervation in an animal model of ALS. Given that sarcopenia shares similarities with ALS in terms of NMJ deterioration, we aimed to investigate whether 2-PMPA treatment could also preserve muscle function during aging. We measured the activity of GCPII in the gastrocnemius muscles of 4-month-old and 20-month-old mice, and found that GCPII activity was significantly increased in the 20-month-old mice (3188±182 fmol/mg/h) compared to 4-month-old mice (2009±317 fmol/mg/h). Then we treated 15-month-old C57BL6/J mice with 100mg/kg of 2-PMPA IP daily for 5 months and monitored muscle function. After 5 months of 2-PMPA treatment, we observed preservation of gastrocnemius muscle mass (164.8±5.6 vs. 143.6±6.4 mg, 2-PMPA vs. vehicle treated group) and a significant delay in age-related loss in grip strength (-4.75±3.22% vs. -20.98±3.73%, 2-PMPA vs. vehicle). We also found that 2-PMPA treatment increased the mean single-fiber cross-sectional area (759.4±5.2 vs. 722.4±5.1 μm2, 2-PMPA vs. vehicle), delayed the decline of nerve signals to the muscles as observed by compound muscle action potential (CMAP) amplitude decline (-7.37±6.16% vs. -26.05±3.71%, 2-PMPA vs. vehicle), and improved ambulation in old mice (3941±153 vs. 3216±188 beam brakes, 2-PMPA vs. vehicle) as observed by open-field test. Immunofluorescent staining showed that GCPII expression in aged muscle is associated with infiltrating macrophages, indicating inflammation as one potential target for the role of 2-PMPA in preserving muscle function during aging. Overall, our current results support that excessive GCPII activity is associated with muscle aging and GCPII inhibition is a potential therapeutic strategy for sarcopenia. This study highlights the potential of GCPII inhibition as a new therapeutic approach to preserving muscle function in the elderly. This work was supported by NIH R01 AG078181-01 (to BSS), R01 AG068130 (to BSS), R01NS093416 (to BSS), and R25GM109441 (Hopkins PREP support for TRJ). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Co-exposure to cannabis and nicotine during pregnancy alters fetal lung development
Authors: El Alam Imad , Belgacemi Randa , Rehan Virender , Glass Ian , Danopoulos Soula , Alalam Denise 
Published: May 2023

Rationale: The co-use of cigarettes and cannabis is increasing especially in regions where recreational marijuana use has become legal. However, the use of these dependent substances during pregnancy poses a serious risk on fetal development and health (low birth weight, preterm birth, and perinatal death). Nevertheless, the impact of co-exposure to the most prominent cannabinoids found in Cannabis sativa (Trans-Δ-9-tetrahydrocannabinol (THC) and cannabidiol (CBD)) with nicotine on fetal lung development is not well understood. This study aims to determine the effect of nicotine, CBD, and THC, alone or combined, on human lung development through investigating cellular senescence. Methods: In vitro human fetal lung explants from 10–20 weeks gestation were cultured on air-liquid interface and treated with physiological concentrations of CBD, THC, and nicotine, alone or combined, for 72h. Similarly, lung mesenchymal cells (LMCs) were isolated from the same samples and treated for 48h. Both culture types were either fixed for immunofluorescent staining or used for RNA extraction and qRT-PCR. Results: Our results showed that nicotine and CBD induce thickening of the mesenchymal compartment of lung explants. Furthermore, treatment with either CBD or THC, or the two combined, induced an increase in epithelial cysting. Ki-67 staining demonstrated increased proliferation following treatment with nicotine, THC and CBD+THC+nicotine. ACTA2 staining, a marker for smooth muscle cells, decreased following treatment with THC, CBD, and nicotine as well as all 3 combined, while the senescence marker p21 increased following exposure to nicotine, CBD+THC, as well as CBD+THC+nicotine. qRT-PCR data showed decreased expression of ACTA2 in the presence of CBD, THC, CBD+THC, and CBD+THC+nicotine, and increased expression of CDKN1A (encoding p21) and CDKN2A (encoding p16) in response to CBD+THC+nicotine. LMCs treated with nicotine, CBD, and THC demonstrated an increase in cell proliferation and senescence as shown by Ki-67 and p21 staining respectively, and a decrease in ACTA2. These data were confirmed by qRT-PCR that showed a decrease in ACTA2 for the LMCs treated with either nicotine or CBD+THC+nicotine and an increase in senescence genes CDKN1A and CDKN2A. Moreover, the expression of these genes was higher in the LMCs derived from second trimester samples in comparison to those of the first trimester. Conclusion: Our results showed that the co-exposure to nicotine and cannabis induces senescence and alters lung fetal cellular proliferation, especially when used in conjunction. Furthermore, this effect appears to be age dependent. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Lactic acid bacteria and their lysate ameliorate skin inflammation in a UVB irradiation-induced skin photoaging mouse model
Authors: Cheon Se Jin , Kim Jae Young , Kim Gyu Wan , Lee Jung Yun , Kim Sae Hun 
Published: May 2023

Skin photoaging is premature skin aging caused by over exposure to ultraviolet (UV) radiation. Photoaged skin is characterized by epidermal thickening, dryness, deep wrinkles, loss of elasticity, delayed wound healing and susceptibility to cancer and closely related to skin inflammation. Meanwhile, it had been reported that lactic acid bacteria (LAB) lysate has lots of beneficial components such as fatty acid, vitamin B, and amino acids, and LAB has the anti-inflammatory effects and the potentials as therapeutics for many chronic inflammatory diseases. Because skin photoaging is recovered by reducing inflammation, co-treatment of LAB and their lysate may alleviate the skin conditions caused by UV-induced skin photoaging via the anti-inflammatory effects. Therefore, the aim of this study is to find out whether co-treatment of LAB and their lysate has beneficial effects on skin conditions and ameliorates skin photoaging. LAB and their lysate were treated in vitro and in vivo. LAB lysate decreased the expression levels of pro-inflammatory cytokines including TNF-α and other inflammation-related biomarkers such as cyclooxygenase 2 (COX-2) and toll-like receptor 4 (TLR4) significantly in HaCaT, the human keratinocyte cell line. LAB and their lysate was evaluated in UVB-induced skin photoaged HR-1 mice model, and it decreased the pro-inflammatory cytokines including TNF-α in serum. LAB and their lysate also decreased pro-inflammatory cytokines in skin, colon, and spleen. Moreover, LAB and their lysate changed the composition of fecal microbiome and short chain fatty acids in mice. In conclusion, the topical treatment of lactic acid bacteria and their lysate may have a potential to ameliorate skin photoaging by reducing inflammation. This work was supported by Korea Testing Laboratory This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Probiotics supplementation attenuates high cholesterol diet-induced hypercholesterolemia in rat model
Authors: Seo Eun Jin , Kim Jae Young , Kim Sae Hun 
Published: May 2023

Hypercholesterolemia is characterized by elevated total serum cholesterol levels, reflecting a high LDL (low-density lipoprotein cholesterol) level, a high TG (triglyceride) level and a low HDL (high-density lipoprotein cholesterol) level. Hypercholesterolemia may cause cardiovascular diseases such as heart attack, stroke and coronary artery diseases. Nowadays, several drugs like statins that lower serum cholesterol are used to treat hypercholesterolemia. However, the cholesterol-lowering drugs have side effects including liver damage and kidney failure. For these reasons, alternatives like probiotics are expected to attenuate hypercholesterolemia instead. Recent studies have shown that probiotics protect against hypercholesterolemia and liver dysfunction via gut-liver axis. Probiotics such as lactic acid bacteria (LAB) may modulate gut microbiota, regulate lipid metabolism and lead to alleviate liver disease. This study aims to determine whether LABs have a protective effect on hypercholesterolemia. LAB strains were selected by acid tolerance, bile tolerance, and antibiotic activity through in vitro screening. 6-week SD rats were fed normal diet or high cholesterol diet (HCD) for 7 weeks. Treatment groups were fed HCD with statin and LABs respectively. LAB supplements effectively improved serum lipid profiles. LABs prevented HCD-induced intestinal and liver damage by enhancing tight junction, reducing inflammation. LABs suppressed lipid accumulation in the liver and enhanced the inhibition of the liver toxicity. Also, LAB supplements changed HCD-induced gut microbiota composition and influenced diversity of gut microbiome. The concentration of bile acid and short chain fatty acids in feces were increased by LAB supplements. Thus, results suggest that LABs are potential therapeutic agents for HCD-induced intestine and liver dysfunction. This work is supported by Cellbiotech Co., Ltd. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Liver Androgen Receptor Knockout Delayed the Onset of High Fructose Diet-Induced Dysglycemia in Female Mice
Authors: Andrisse Stanley 
Published: May 2023

Introduction: Previous research has indicated that a lipid-independent pathogenic mechanism plays a role in androgen-induced hepatic insulin resistance where liver androgen receptors may play a role in modulating disease. Consequently, this study aims to investigate the pathophysiology of high fructose diet (HFrD) induced dysglycemia in male and female liver androgen receptor knockout (LivARKO) mice. Andrisse et al 2021 showed that deleting the liver androgen receptor prevented female mice from developing hyperandrogenemia (HA)-induced insulin resistance. From this, we asked the question, does LivARKO prevent HFrD induced dysglycemia? Hypothesis: It was hypothesized that HFrD LivARKO female mice would display impaired whole body glucose metabolism in comparison to the Control diet fed LivARKO female mice, suggesting that AR does not play a significant role in regulating HFrD-induced dysglycemia.Methods: We performed insulin tolerance tests (ITT), glucose tolerance tests (GTT), pyruvate tolerance tests (PTT), and glucose stimulated insulin secretion (GSIS) tests on LivARKO female mice fed a high fat diet (HFD) or a control diet (CD) (from Research Diets Inc) during months 1 or 2 after starting the diet. Results: After 1-month, LivARKO female mice fed a Control diet had impaired glucose tolerance compared to LivARKO-HFrD female mice; however, after 2-months, the LivARKO-HFrD female mice displayed impaired glucose tolerance above that of the Control diet LivARKO female mice. LivARKO female mice fed a high fructose diet (HFrD) did not display increased fasting insulin levels compared to LivARKO female mice on a control diet. HFrD LivARKO mice did not display any increase in GSIS at 15-min or 30-min. Conclusion: These findings suggest that LivARKO delayed the onset of HFrD-Induced dysglycemia in female mice. Further research may consist of molecular data to elucidate the mechanistic pathways involved in these whole body phenotypes observed. The cellular molecular regulation of differing mechanisms of insulin resistance. 1R01DK126892-01A1 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Blocking purinergic signaling alters platelet and macrophage crosstalk and phagocytic ability in the peritoneal cavity during intra-abdominal sepsis
Authors: Entsie Philomena , Amoafo Emmanuel , Kang Ying , Dorsam Glenn , Liverani Elisabetta 
Published: May 2023

Intra-abdominal sepsis is a life-threatening complex syndrome caused by dysregulation of the host response to infection and is one of the major complications of intra-abdominal surgery. To date, only supportive therapies such as ventilation support, antibiotics and organ replacement are available. However, an increase in antibiotic resistance and the invasiveness of organ transplant has necessitated therapies targeting pathophysiological mechanisms. Platelets, which express the purinergic receptors P2Y1 and P2Y12, mediate macrophage polarization and secretion of pro-inflammatory markers contributing to tissue injury during sepsis. Previously, our group has shown that blocking purinergic signaling through P2Y1 and P2Y12 antagonism significantly lowered inflammatory cytokine levels and improved survival in a murine model of sepsis in a sex specific manner. We hypothesize that the inhibition of P2Y1 and P2Y12 signaling pathways improves the sex-specific outcomes of intra-abdominal sepsis by modulating the crosstalk between platelets and macrophages. Male and female mice underwent sham surgery or cecal ligation and puncture (CLP) to induce sepsis followed by intraperitoneal administration of ticagrelor (P2Y12 antagonist) or MRS2279 (P2Y1 antagonist). The peritoneal cavity fluid (PCF) was collected 4 and 24 hours post-surgery and analyzed. At 4 hours post-surgery, PCF macrophages exhibited increased bacterial phagocytosis from ticagrelor and MRS2279 treated groups in female mice only compared to CLP group. At 24 hours post-CLP surgery, platelet counts did not change but soluble p-selectin and TBX-2 levels were significantly decreased in male groups treated with either ticagrelor or MRS2279, compared to controls. In contrast, soluble p-selectin and TBX-2 levels did not change in female samples.Thus, we conclude that pharmacologically blocking P2Y1 and P2Y12 receptors can enhance the ex-vivo phagocytic activity of macrophages in a sex-related manner, and overall modulate platelet secretion and influence macrophages’ recruitment and activation in the PC during sepsis. National Institute of Health AI156627-01 to EL This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.