Impact of sarcopenia and low muscle attenuation on outcomes of ovarian cancer: a systematic review and meta-analysis.

OBJECTIVE: The aim of this study was to examine the association of sarcopenia and low muscle attenuation with survival and other clinical outcomes in patients with ovarian cancer. MATERIALS AND METHODS: Systematic search was done in PubMed, EMBASE and Scopus databases for observational studies that documented the link between sarcopenia and outcomes of interest in patients with ovarian cancer, with long-term survival as a primary outcome. Other outcomes included risk of recurrence, progression-free survival and complications. Pooled effect sizes were reported as hazards ratio (HR), relative risk ratio (RR) or weighted mean difference (WMD). Random effects model was used for the analysis. RESULTS: Twenty-two studies were selected, of which all, except one, were retrospective in design. Low skeletal muscle index (SMI, indicating muscle mass) (HR 1.30, 95% CI: 1.07, 1.58) and low muscle quality (HR 1.24, 95% CI: 1.03, 1.49) were associated with poor long-term survival, but not with the risk of recurrence and progression-free survival. Both low skeletal muscle index (SMI) (RR 1.49, 95% CI: 1.13, 1.98) and low muscle quality (RR 1.99, 95% CI: 1.04, 3.79) were associated with increased risk of complications. CONCLUSIONS: Both low skeletal muscle mass and low muscle quality showed significant association with poor long-term survival and an increased risk of complications. However, they do not have a significant association with the risk of recurrence and progression-free survival. There is a need for more prospective studies to confirm these associations.

MicroRNA-206 facilitates gastric cancer cell apoptosis and suppresses cisplatin resistance by targeting MAPK2 signaling pathway.

OBJECTIVE: Mitogen activating protein kinase 3 (MAPK3) is critical in extracellular signal-regulated kinase (ERK)/MAPK pathway. Gastric cancer tissues have microRNA-206 (miR-206) down-regulation. This study aimed to investigate the role of miR-206 in MAPK3 expression, gastric cancer cell proliferation, apoptosis, and cisplatin (DDP) resistance. MATERIALS AND METHODS: Dual-Luciferase reporter gene assay confirmed targeted regulation between miR-206 and MAPK3. DDP resistant cell line BGC823/DDP and SGC7901/DDP were generated for comparing miR-206 and MAPK3 expression against parental cells using quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) and Western blot, followed by flow cytometry measuring apoptosis. Drug-resistant cells were transfected with miR-206 mimic for measuring MAPK3 and phosphorylated MAPK3 (p-MAPK3) expression. Flow cytometry and EdU were employed for measuring cell apoptosis and proliferation. RESULTS: Targeted regulation existed between miR-206 and MAPK3 mRNA. BGC823/DDP and SGC7901/DDP cell presented lower miR-206 than parental cells, plus higher MAPK3 mRNA or protein. Under DDP treatment equivalent to IC50 of parental cells, drug-resistant cells presented lower apoptosis compared to parental drug-sensitive cells. Compared to miR-normal control (miR-NC) group, miR-206 mimic transfection significantly decreased MAPK3 and p-MAPK3 protein expression (p < 0.05), enhanced cell apoptosis and weakened proliferation potency (p < 0.05). CONCLUSIONS: The down-regulation of miR-206 is associated with DDP resistance of gastric cancer cells. Up-regulating miR-2016 expression can weaken the proliferation of drug-resistant gastric cancer cells, facilitate cell apoptosis and decrease DDP resistance via targeted inhibition of MAPK3 expression.

Mutational analysis of positively charged residues in the N-terminal region of the class IIa bacteriocin pediocin PA-1.

UNLABELLED: The significance of positively charged residues for the target cell binding of pediocin PA-1 bacteriocins was studied by site-directed mutagenesis. Most of the charged residues are located in the N-terminal half of the peptide, which is thought to mediate the initial binding of these bacteriocins to their target cells through electrostatic interactions. Mutated peptides in which the positively charged residues were substituted or increased in number were constructed, and some of these peptides exhibited a twofold increase in the bacteriostatic activity. The greatest enhancement was achieved by introduced the positive charges at position 13, their results show the benefits of introducing an additional cationic residue within this patch in the middle of the N-terminal half of pediocin PA-1 bacteriocins. Thus, the presence of additional cationic residues in the N-terminal half influenced the electrostatic binding of this bacteriocin to its target cells and increased the potency of the peptide on the potency of Micrococcus luteus and Staphylococcus aureus. SIGNIFICANCE AND IMPACT OF THE STUDY: No previous work has systematically examined the N-terminal cationic residues of the pediocin PA-1 for their functional importance or redundancy. In this study, we examined the structure-function relationships of pediocin PA-1 by site-directed mutagenesis. Mutated peptides in which the positively charged residues were substituted and increased in number exhibited a twofold increase in the bacteriostatic activity. This study demonstrated the importance of the cationic patch in the N-terminal half of pediocin PA-1. The cationic residues influenced the electrostatic binding of the bacteriocin to the target cells and had a greater effect on the potency of the peptide towards Micrococcus luteus and Staphylococcus aureus.