Effects of Cycling Intensity on Acute Signaling Adaptations to 8-weeks Concurrent Training in Trained Cyclists

© 2022 Jones, Eddens, Kupusarevic, Simoes, Furber, Van Someren and Howatson. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). https://creativecommons.org/licenses/by/4.0/This study examined whether the intensity of endurance stimuli modifies the adaptation in strength and endurance following concurrent training and whether the acute molecular response to concurrent exercise is affected by training status. Using a parallel group design, trained cyclists were randomized to either resistance exercise followed by moderate intensity continuous training (RES + MICT, n = 6), or resistance exercise followed by work matched high intensity interval training (RES + HIIT, n = 7), across an 8 weeks training programme. A single RES + MICT or RES + HIIT exercise stimulus was completed 1 week before and within 5 days of completing the training programme, to assess phosphorylation of protein kinases of the mTOR and AMPK signaling pathways. There were no main effects of time or group on the phosphorylation of protein kinases in response to concurrent exercise stimulus pre- and post-training intervention (p > 0.05). Main effects of time were observed for all maximal strength exercises; back-squat, split-squat, and calf-raise (p 0.05). Whilst preliminary data due to limited sample size the intensity of endurance activity had no effect on performance outcomes, following concurrent training. Further, the acute molecular response to a concurrent exercise stimulus was comparable before and after the training intervention, suggesting that training status had no effect on the molecular responses assessed.Peer reviewedFinal Published versio

Aerobic exercise intensity does not affect the anabolic signaling following resistance exercise in endurance athletes

Abstract: This study examined whether intensity of endurance stimulus within a concurrent training paradigm influenced the phosphorylation of signaling proteins associated with the mTOR and AMPK networks. Eight male cyclists completed (1) resistance exercise (RES), 6 × 8 squats at 80% 1-RM; (2) resistance exercise and moderate intensity cycling of 40 min at 65% V̇O2peak, (RES + MIC); (3) resistance exercise and high intensity interval cycling of 40 min with 6 alternating 3 min intervals of 85 and 45% V̇O2peak (RES + HIIC), in a cross-over design. Muscle biopsies were collected at rest and 3 h post-RES. There was a main effect of condition for mTORS2448 (p = 0.043), with a greater response in the RES + MIC relative to RES condition (p = 0.033). There was a main effect of condition for AMPKα2T172 (p = 0.041), with a greater response in RES + MIC, relative to both RES + HIIC (p = 0.026) and RES (p = 0.046). There were no other condition effects for the remaining protein kinases assessed (p > 0.05). These data do not support a molecular interference effect in cyclists under controlled conditions. There was no intensity-dependent regulation of AMPK, nor differential activation of anabolism with the manipulation of endurance exercise intensity.Peer reviewe

B Cells Regulate Neutrophilia during Mycobacterium tuberculosis Infection and BCG Vaccination by Modulating the Interleukin-17 Response

We have previously demonstrated that B cells can shape the immune response to Mycobacterium tuberculosis, including the level of neutrophil infiltration and granulomatous inflammation at the site of infection. The present study examined the mechanisms by which B cells regulate the host neutrophilic response upon exposure to mycobacteria and how neutrophilia may influence vaccine efficacy. To address these questions, a murine aerosol infection tuberculosis (TB) model and an intradermal (ID) ear BCG immunization mouse model, involving both the μMT strain and B cell-depleted C57BL/6 mice, were used. IL (interleukin)-17 neutralization and neutrophil depletion experiments using these systems provide evidence that B cells can regulate neutrophilia by modulating the IL-17 response during M. tuberculosis infection and BCG immunization. Exuberant neutrophilia at the site of immunization in B cell-deficient mice adversely affects dendritic cell (DC) migration to the draining lymph nodes and attenuates the development of the vaccine-induced Th1 response. The results suggest that B cells are required for the development of optimal protective anti-TB immunity upon BCG vaccination by regulating the IL-17/neutrophilic response. Administration of sera derived from M. tuberculosis-infected C57BL/6 wild-type mice reverses the lung neutrophilia phenotype in tuberculous μMT mice. Together, these observations provide insight into the mechanisms by which B cells and humoral immunity modulate vaccine-induced Th1 response and regulate neutrophila during M. tuberculosis infection and BCG immunization. © 2013 Kozakiewicz et al

High Mortality of Pneumonia in Cirrhotic Patients with Ascites

[[abstract]]Background Cirrhotic patients with ascites are prone to develop various infectious diseases. This study aimed to evaluate the occurrence and effect of major infectious diseases on the mortality of cirrhotic patients with ascites. Methods We reviewed de-identified patient data from the National Health Insurance Database, derived from the Taiwan National Health Insurance Program, to enroll 4,576 cirrhotic patients with ascites, who were discharged from Taiwan hospitals between January 1, 2004 and June 30, 2004. We collected patients’ demographic and clinical data, and reviewed diagnostic codes to determine infectious diseases and comorbid disorders of their hospitalizations. Patients were divided into an infection group and non-infection group and hazard ratios (HR) were determined for specific infectious diseases. Results Of the total 4,576 cirrhotic patients with ascites, 1,294 (28.2%) were diagnosed with infectious diseases during hospitalization. The major infectious diseases were spontaneous bacterial peritonitis (SBP) (645, 49.8%), urinary tract infection (151, 11.7%), and pneumonia (100, 7.7%). After adjusting for patients’ age, gender, and other comorbid disorders, the HRs of infectious diseases for 30-day and 90-day mortality of cirrhotic patients with ascites were 1.81 (1.54-2.11) and 1.60 (1.43-1.80) respectively, compared to those in the non-infection group. The adjusted HRs of pneumonia, urinary tract infection (UTI), spontaneous bacterial peritonitis (SBP), and sepsis without specific focus (SWSF) were 2.95 (2.05-4.25), 1.32 (0.86-2.05), 1.77 (1.45-2.17), and 2.19 (1.62-2.96) for 30-day mortality, and 2.57 (1.93-3.42), 1.36 (1.01-1.82), 1.51 (1.29-1.75), and 2.13 (1.70-2.66) for 90-day mortality, compared to those in the non-infection group. Conclusion Infectious diseases increased 30-day and 90-day mortality of cirrhotic patients with ascites. Among all infectious diseases identified, pneumonia carried the highest risk for mortality.[[notice]]補正完畢[[incitationindex]]SCI[[booktype]]電子

Malassezia restricta pneumonia in solid organ transplant recipients: First report of two cases

Emerging fungal infections are a major challenge in solid organ transplantation (SOT) and are associated with high morbidity and mortality. We report two cases of Malassezia restricta pneumonia in SOT recipients. Infections were diagnosed with molecular analysis and histology. Patients were treated with antifungal therapy and have fully recovered

Pneumocystis-Driven Inducible Bronchus-Associated Lymphoid Tissue Formation Requires Th2 and Th17 Immunity

Inducible bronchus-associated lymphoid tissue (iBALT) is an ectopic lymphoid structure composed of highly organized T cell and B cell zones that forms in the lung in response to infectious or inflammatory stimuli. Here, we develop a model for fungal-mediated iBALT formation, using infection with Pneumocystis that induces development of pulmonary lymphoid follicles. Pneumocystis-dependent iBALT structure formation and organization required CXCL13 signaling. Cxcl13 expression was regulated by interleukin (IL)-17 family members, as Il17ra−/−, Il17rb−/−, and Il17rc−/− mice failed to develop iBALT. Interestingly, Il17rb−/− mice have intact Th17 responses, but failed to generate an anti-Pneumocystis Th2 response. Given a role for Th2 and Th17 immunity in iBALT formation, we demonstrated that primary pulmonary fibroblasts synergistically upregulated Cxcl13 transcription following dual stimulation with IL-13 and IL-17A in a STAT3/GATA3-dependent manner. Together, these findings uncover a role for Th2/Th17 cells in regulating Cxcl13 expression and provide an experimental model for fungal-driven iBALT formation

FSTL-1 Attenuation Causes Spontaneous Smoke-Resistant Pulmonary Emphysema

Rationale: The role of FSTL-1 (follistatin-like 1) in lung homeostasis is unknown.Objectives: We aimed to define the impact of FSTL-1 attenuation on lung structure and function and to identify FSTL-1-regulated transcriptional pathways in the lung. Further, we aimed to analyze the association of FSTL-1 SNPs with lung disease.Methods: FSTL-1 hypomorphic (FSTL-1 Hypo) mice underwent lung morphometry, pulmonary function testing, and micro-computed tomography. Fstl1 expression was determined in wild-type lung cell populations from three independent research groups. RNA sequencing of wild-type and FSTL-1 Hypo mice identified FSTL-1-regulated gene expression, followed by validation and mechanistic in vitro examination. FSTL1 SNP analysis was performed in the COPDGene (Genetic Epidemiology of Chronic Obstructive Pulmonary Disease) cohort.Measurements and Main Results: FSTL-1 Hypo mice developed spontaneous emphysema, independent of smoke exposure. Fstl1 is highly expressed in the lung by mesenchymal and endothelial cells but not immune cells. RNA sequencing of whole lung identified 33 FSTL-1-regulated genes, including Nr4a1, an orphan nuclear hormone receptor that negatively regulates NF-κB (nuclear factor-κB) signaling. In vitro, recombinant FSTL-1 treatment of macrophages attenuated NF-κB p65 phosphorylation in an Nr4a1-dependent manner. Within the COPDGene cohort, several SNPs in the FSTL1 region corresponded to chronic obstructive pulmonary disease and lung function.Conclusions: This work identifies a novel role for FSTL-1 protecting against emphysema development independent of smoke exposure. This FSTL-1-deficient emphysema implicates regulation of immune tolerance in lung macrophages through Nr4a1. Further study of the mechanisms involving FSTL-1 in lung homeostasis, immune regulation, and NF-κB signaling may provide additional insight into the pathophysiology of emphysema and inflammatory lung diseases