Background: Exercise changes the concentrations of many metabolites, which are small molecules (< 1.5 kDa) metabolized by the reactions of human metabolism. In recent years, especially mass spectrometry-based metabolomics methods have allowed researchers to measure up to hundreds of metabolites in a single sample in a non-biased fashion. To summarize human exercise metabolomics studies to date, we conducted a systematic review that reports the results of experiments that found metabolite concentrations changes after a bout of human endurance or resistance exercise.Methods: We carried out a systematic review following PRISMA guidelines and searched for human metabolomics studies that report metabolite concentrations before and within 24 h after endurance or resistance exercise in blood, urine, or sweat. We then displayed metabolites that significantly changed their concentration in at least two experiments. Results: Twenty-seven studies and 57 experiments matched our search criteria and were analyzed. Within these studies, 196 metabolites changed their concentration significantly within 24 h after exercise in at least two experiments. Human biofluids contain mainly unphosphorylated metabolites as the phosphorylation of metabolites such as ATP, glycolytic intermediates, or nucleotides traps these metabolites within cells. Lactate, pyruvate, TCA cycle intermediates, fatty acids, acylcarnitines, and ketone bodies all typically increase after exercise, whereas bile acids decrease. In contrast, the concentrations of proteinogenic and non-proteinogenic amino acids change in different directions.Conclusion: Across different exercise modes and in different subjects, exercise often consistently changes the average concentrations of metabolites that belong to energy metabolism and other branches of metabolism. This dataset is a useful resource for those that wish to study human exercise metabolism.

VGLL proteins are transcriptional co-factors that bind TEAD family transcription factors to regulate events ranging from wing development in fly, to muscle fibre composition and immune function in mice. Here, we characterise Vgll3 in skeletal muscle. We found that mouse Vgll3 was expressed at low levels in healthy muscle but that its levels increased during hypertrophy or regeneration; in humans, VGLL3 was highly expressed in tissues from patients with various muscle diseases, such as in dystrophic muscle and alveolar rhabdomyosarcoma. Interaction proteomics revealed that VGLL3 bound TEAD1, TEAD3 and TEAD4 in myoblasts and/or myotubes. However, there was no interaction with proteins from major regulatory systems such as the Hippo kinase cascade, unlike what is found for the TEAD co-factors YAP (encoded by YAP1 ) and TAZ (encoded by WWTR1 ). Vgll3 overexpression reduced the activity of the Hippo negative-feedback loop, affecting expression of muscle-regulating genes including Myf5 , Pitx2 and Pitx3 , and genes encoding certain Wnts and IGFBPs. VGLL3 mainly repressed gene expression, regulating similar genes to those regulated by YAP and TAZ. siRNA-mediated Vgll3 knockdown suppressed myoblast proliferation, whereas Vgll3 overexpression strongly promoted myogenic differentiation. However, skeletal muscle was overtly normal in Vgll3 -null mice, presumably due to feedback signalling and/or redundancy. This work identifies VGLL3 as a transcriptional co-factor operating with the Hippo signal transduction network to control myogenesis.

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A phase II pilot study of bendamustine as salvage treatment in patients with advanced breast cancer was performed to determine the objective response rates and make further observations on the toxicity of this drug. A group of 37 patients, pretreated with chemotherapy for advanced disease, entered the trial. Treatment consisted of 150 mg/m2 bendamustine on days 1 and 2 of a 4-week treatment course. Patients continued to receive treatment until complete remission and then two further courses, until tumour progression or unacceptable toxicity ensued. A total of 36 patients received at least one treatment course and were assessable for toxicity; 33 patients were evaluable for treatment results. Dose-limiting grade 3 and 4 WHO toxicity occurred in 5 and 3 patients respectively; 27% of patients entered complete or partial tumour remission. The median time to tumour progression was 2 months with a range of 1-14 months. The efficacy of bendamustine was apparently independent of pretreatment with anthracyclines, suggesting a lack of cross-resistance between bendamustine and anthracyclines. It can be concluded that bendamustine in the dose and application schedule used here is active in the salvage therapy of women with advanced breast cancer. The toxicity was acceptable. Future studies have to confirm the data of this pilot trial and to define the role of bendamustine in the combination chemotherapy of metastatic breast cancer that has been suggested by previous trials.

This document provides guidance to EU/EEA Member States on environmental cleaning in healthcare and nonhealthcare settings during the COVID-19 pandemic.

Endurance training protocols assessed in this study all led to significant increases in peak work capacity of comparable magnitude. Our findings suggest that these protocols can be used interchangeably, which will lead to further individualization of exercise prescription and may therefore result in improved adherence to lifelong behavioural changes.

Skeletal muscle mass differs greatly in mice and humans and this is partially inherited. To identify muscle hypertrophy candidate genes we conducted a systematic review to identify genes whose experimental loss or gain-of-function results in significant skeletal muscle hypertrophy in mice. We found 47 genes that meet our search criteria and cause muscle hypertrophy after gene manipulation. They are from high to small effect size: Ski, Fst, Acvr2b, Akt1, Mstn, Klf10, Rheb, Igf1, Pappa, Ppard, Ikbkb, Fstl3, Atgr1a, Ucn3, Mcu, Junb, Ncor1, Gprasp1, Grb10, Mmp9, Dgkz, Ppargc1a (specifically the Ppargc1a4 isoform), Smad4, Ltbp4, Bmpr1a, Crtc2, Xiap, Dgat1, Thra, Adrb2, Asb15, Cast, Eif2b5, Bdkrb2, Tpt1, Nr3c1, Nr4a1, Gnas, Pld1, Crym, Camkk1, Yap1, Inhba, Tp53inp2, Inhbb, Nol3, Esr1. Knock out, knock down, overexpression or a higher activity of these genes causes overall muscle hypertrophy as measured by an increased muscle weight or cross sectional area. The mean effect sizes range from 5 to 345% depending on the manipulated gene as well as the muscle size variable and muscle investigated. Bioinformatical analyses reveal that Asb15, Klf10, Tpt1 are most highly expressed hypertrophy genes in human skeletal muscle when compared to other tissues. Many of the muscle hypertrophy-regulating genes are involved in transcription and ubiquitination. Especially genes belonging to three signaling pathways are able to induce hypertrophy: (a) Igf1-Akt-mTOR pathway, (b) myostatin-Smad signaling, and (c) the angiotensin-bradykinin signaling pathway. The expression of several muscle hypertrophy-inducing genes and the phosphorylation of their protein products changes after human resistance and high intensity exercise, in maximally stimulated mouse muscle or in overloaded mouse plantaris.

A complete VEGF system consisting of the ligand and two of its receptors has been detected for the first time in the bovine cumulus-oocyte-complex (COC). In the course of a 24 hr in vitro maturation procedure (IVM), expression of the smaller VEGF transcripts and their specific receptors flt and flk changed remarkably in a time-dependent manner as observed by RT-PCR. The transcript concentrations of VEGF declined within 24 hr of culture, whereas both receptor mRNAs were found enriched between 6 and 12 hr of IVM. In the follicular fluid of growing ovarian follicles, immunoreactive VEGF, measured by RIA, increased significantly, reaching highest concentrations immediately before ovulation of the oocyte. The immunohistochemical localization of VEGF in bovine COCs revealed strong signals within the cumulus cell complex clearly extending beyond the oocyte cytoplasm at the beginning of in vitro maturation. After 24 hr, IVM immunoreactive VEGF disappeared remarkably from cumulus cells and the oocyte cytoplasm. An exogenous application of VEGF at the beginning of a 24 hr IVM significantly improved cleavage rates of zygotes and their development into bovine embryos showing obvious synergistic effects in combination with FSH, when compared with untreated control embryos. In addition, the number of blastomeres in deriving blastocysts increased after VEGF supplementation. These results indicate a functional VEGF system controlling important events beside the known angiogenetic effect during in vivo and in vitro maturation of the bovine COC, possibly affecting the early embryonic viability.