Proteomic Profiling of Muscular Adaptations to Short-Term Concentric Versus Eccentric Exercise Training in Humans.

The molecular mechanisms underlying muscular adaptations to concentric (CON) and eccentric (ECC) exercise training have been extensively explored. However, most previous studies have focused on specifically selected proteins, thus, unable to provide a comprehensive protein profile and potentially missing the crucial mechanisms underlying muscular adaptation to exercise training. We herein aimed to investigate proteomic profiles of human skeletal muscle in response to short-term resistance training. Twenty young males were randomly and evenly assigned to two groups to complete a 4-week either ECC or CON training program. Measurements of body composition and physiological function of the quadriceps femoris were conducted both before and after the training. Muscle biopsies from the vastus lateralis of randomly selected participants (five in ECC and four in CON) of both before and after the training were analyzed using the liquid-chromatography tandem mass spectrometry in combination with bioinformatics analysis. Neither group presented a significant difference in body composition or leg muscle mass; however, muscle peak torque, total work, and maximal voluntary contraction were significantly increased after the training in both groups. Proteomics analysis revealed 122 differentially abundant proteins (DAPs; p value < 0.05 & fold change >1.5 or <0.67) in ECC, of which the increased DAPs were mainly related to skeletal muscle contraction and cytoskeleton and enriched specifically in the pentose phosphate pathway, extracellular matrix-receptor interaction, and PI3K-Akt signaling pathway, whereas the decreased DAPs were associated with the mitochondrial respiratory chain. One hundred one DAPs were identified in CON, of which the increased DAPs were primarily involved in translation/protein synthesis and the mitochondria respiratory, whereas the decreased DAPs were related to metabolic processes, cytoskeleton, and de-ubiquitination. In conclusion, the 4-week CON and ECC training resulted in distinctly different proteomic profiles, especially in proteins related to muscular structure and metabolism.

Hypoxic re-exposure retains hematological but not performance adaptations post-altitude training.

PURPOSE: To test the hypothesis that hypoxic re-exposure after return from natural altitude training is beneficial in retaining hematological and performance adaptations. METHODS: Eighteen mixed martial art fighters completed a 3-weeks natural altitude training camp at 2418 m. Afterwards, participants were randomly assigned to a living high-training low (12 h/d at a simulated altitude of 2800 m) group (LHTL, n = 9) or a living low-training low group (LLTL, n = 9) for a 3-week sea-level training period. At baseline and after return to sea level, hematological [hemoglobin mass (Hbmass) on days 2, 6, 9, 12, 15 and 21] and performance (3000 m time trial and maximal oxygen uptake on days 4, 6, 9, 15 and 21) markers were assessed. RESULTS: Mean Hbmass increased from baseline to day 2 (11.7 ± 0.9 vs. 12.4 ± 1.3 g/kg; + 6.6 ± 7.5%; P < 0.05). While Hbmass remained elevated above baseline in LHTL (P < 0.001), it returned near baseline levels from day 9 in LLTL. Irrespective of groups, mean V̇O2max was only elevated above baseline at day 2 (+ 4.5 ± 0.8%) and day 9 (+ 3.8 ± 8.0%) (both P < 0.05). Compared to baseline, 3000 m running time decreased at day 4 (- 3.1 ± 3.3%; P < 0.05) and day 15 (- 2.8 ± 2.3%; P < 0.05) only. CONCLUSIONS: Despite re-exposure to hypoxia allowing a recovery of the hypoxic stimulus to retain Hbmass gains from previous altitude sojourn, there is no performance advantage of this practice above sea level residence. Our results also give support to empirical observations describing alternance of periods of optimal and attenuated performance upon return to sea level.

Upregulation of WEE1 is a potential prognostic biomarker for patients with colorectal cancer.

WEE1 is a serine/threonine protein kinase that inactivates cell division cycle 2 and is therefore a critical cell cycle regulator. Increased WEE1 expression has been observed in numerous types of human malignancies, including hepatocellular carcinoma and melanoma. WEE1 inhibition also results in evident anti-tumor effects in several human tumor cells including colon cancer cells, suggesting WEE1 as a potential therapeutic target for the treatment of cancer. However, the expression pattern of WEE1 in colorectal cancer (CRC) remains unclear. In the present study, WEE1 mRNA expression in 43 cases of CRC tissues matched with adjacent normal tissues was determined by reverse-transcription quantitative polymerase chain reaction. The results demonstrated that WEE1 mRNA expression was significantly increased in CRC tissues and that this upregulation correlated significantly with hepatic metastasis, distant metastasis and high tumor node metastasis (TNM) stage of CRC. Additionally, WEE1 protein in 102 CRC tissue samples was detected by immunohistochemistry, and positive staining of WEE1 was identified in more than half of patients with CRC. WEE1 staining scores were also observed to be associated with distant metastasis and high TNM stage of CRC. In addition, patients with CRC with high WEE1 staining score (2+ or 3+) exhibited either poorer overall survival or poorer disease-free survival compared with those with low WEE1 staining score (0 or 1+). The multivariable Cox model also identified a high WEE1 staining score as well as high TNM stage to be independent prognostic factors for CRC. In conclusion, WEE1 upregulation is associated with a high degree of malignancy and poor prognosis of CRC, suggesting WEE1 as a potential prognostic biomarker for CRC.

Mus81 knockdown improves chemosensitivity of hepatocellular carcinoma cells by inducing S-phase arrest and promoting apoptosis through CHK1 pathway.

As a critical endonuclease in DNA repair, Mus81 is traditionally regarded as a tumor suppressor, but recently correlated with the sensitivity of mitomycin C and 5-fluorouracil in colon cancer and breast cancer cells. However, its role in chemosensitivity of other human malignancies still remains unknown. This study therefore aims to investigate the effects of Mus81 knockdown on the chemosensitivity of hepatocellular carcinoma (HCC), a usually chemorefractory tumor, and explore the underlying mechanisms. Mus81 expression in HepG2 and Bel-7402 HCC cell lines was depleted by lentivirus-mediated short hairpin RNA and the elevated sensitivity of these Mus81-inhibited HCC cells to therapeutic agents, especially to epirubicin (EPI), was evidenced by MTT assay and an HCC chemotherapy mouse model. Flow cytometric analysis also showed that Mus81 knockdown lead to an obvious S-phase arrest and an elevated apoptosis in EPI-treated HepG2 and Bel-7402 cells, which could be rescued by CHK1 inhibition. The activation of CHK1/CDC25A/CDK2 pathway was also demonstrated in Mus81-inhibited HepG2 cells and xenograft mouse tumors under EPI treatment. Meanwhile, the apoptosis of HepG2 cells in response to EPI was remarkably promoted by Mus81 knockdown through activating p53/Bax/Caspase-3 pathway under the controlling of CHK1. In addition, CHK2 inhibition slightly raised CHK1 activity, thereby enhancing the S-phase arrest and apoptosis induced by EPI in Mus81-suppressed HCC cells. In conclusion, Mus81 knockdown improves the chemosensitivity of HCC cells by inducing S-phase arrest and promoting apoptosis through CHK1 pathway, suggesting Mus81 as a novel therapeutic target for HCC.

Accurate and inexpensive prediction of the color optical properties of anthocyanins in solution.

The simulation of the color optical properties of molecular dyes in liquid solution requires the calculation of time evolution of the solute absorption spectra fluctuating in the solvent at finite temperature. Time-averaged spectra can be directly evaluated by combining ab initio Car-Parrinello molecular dynamics and time-dependent density functional theory calculations. The inclusion of hybrid exchange-correlation functionals, necessary for the prediction of the correct transition frequencies, prevents one from using these techniques for the simulation of the optical properties of large realistic systems. Here we present an alternative approach for the prediction of the color of natural dyes in solution with a low computational cost. We applied this approach to representative anthocyanin dyes: the excellent agreement between the simulated and the experimental colors makes this method a straightforward and inexpensive tool for the high-throughput prediction of colors of molecules in liquid solvents.