Resveratrol has been shown to exert anti-inflammatory and anti-oxidant effects in a variety of cell types, however, its role in prevention of inflammatory responses mediated by palmitate in skeletal muscle cells remains unexplored. In the present study, we investigated the effects of resveratrol on palmitate-induced inflammation and elucidated the underlying mechanisms in skeletal muscle cells. The results showed that palmitate significantly enhanced TNF-α and IL-6 mRNA expression and protein secretion from C2C12 cells at 12, 24, and 36 h treatments. Increased expression of cytokines was accompanied by an enhanced phosphorylation of JNK, P38, ERK1/2, and IKKα/IKKβ. In addition, JNK and P38 inhibitors could significantly attenuate palmitate-induced mRNA expression of TNF-α and IL-6, respectively, whereas NF-κB inhibitor reduced the expression of both cytokines in palmitate-treated cells. Resveratrol pretreatment significantly prevented palmitate-induced TNF-α and IL-6 mRNA expression and protein secretion in C2C12 cells. Importantly, pre-treatment of the cells with resveratrol completely abrogated the phosphorylation of ERK1/2, JNK, and IKKα/IKKβ in palmitate treated cells. The protection from palmitate-induced inflammation by resveratrol was accompanied by a decrease in the generation of reactive oxygen species (ROS). N-acetyl cysteine (NAC), a known scavenger of ROS, could protect palmitate-induced expression of TNF-α and IL-6. Furthermore, inhibition of SIRT1 by shRNA or sirtinol demonstrated that the anti-inflammatory effect of resveratrol in muscle cells is mediated through a SIRT1-independent mechanism. Taken together, these findings suggest that resveratrol may represent a promising therapy for prevention of inflammation in skeletal muscle cells. J. Cell. Biochem. 118: 2654-2663, 2017. © 2017 Wiley Periodicals, Inc.

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There is no consensus regarding the clinical significance of CD44 and CD24 as cancer stem cell (CSC) marker in colorectal cancer (CRC). Methodology: A total of 494 CRC samples (2008)(2009)(2010)(2011)(2012)(2013)(2014)(2015)(2016)(2017) were assessed for CD44 (epithelial isoform) and CD24 expression using tissue microarray. Results: CD24 individually or in combination with CD44 was not associated with any of the clinicopathologic characteristics of the tumor. CD44 expression was inversely associated with pathological Tumor, Node, Metastasis (pTNM) lower stages (p = 0.038) and lymphatic invasion (p = 0.05). Conclusion: In summary, the epithelial isoform of CD44 is inversely associated with invasive characteristics of CRC.

Resveratrol was reported to inhibit inflammatory responses; however, the role of this polyphenol in obesity-induced skeletal muscle inflammation remains unknown. Mice fed a high fat diet (HFD) were treated with resveratrol for 16 weeks. Resveratrol treatment decreased macrophage infiltration into skeletal muscle of HFD-fed mice. Resveratrol also led to the polarization of macrophages to the M2 direction, as well as decreasing the expression of a number of M1 pro-inflammatory cytokines [tumor necrosis factor α (TNF-α), interleukin 1 β (IL-1β) and interleukin 6 (IL-6)]. In addition, increased infiltration of regulatory T cells (Treg cells) was found following resveratrol treatment in skeletal muscle of mice. Decreased intramyocellular lipid deposition was associated with reduced expression levels of toll-like receptors 2 (TLR2) and TLR4 in resveratrol treated mice. We also found that diminished inflammation in skeletal muscle following resveratrol treatment was accompanied by increasing phosphorylation of 5'-adenosine monophosphate-activated protein kinase (AMPK) and decreasing phosphorylation of p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK). Taken together, these findings suggest that resveratrol ameliorates inflammation in skeletal muscle of HFD-induced model of obesity. Therefore, resveratrol might represent a potential treatment for attenuation of inflammation in skeletal muscle tissue.

Curcumin, a natural polyphenol compound, has the beneficial effects on several diseases such as metabolic syndrome, cancer, and diabetes. The anti-inflammatory property of curcumin has been demonstrated in different cells; however, its role in prevention of palmitate-induced inflammation in skeletal muscle C2C12 cells is not known. In this study, we examined the effect of curcumin on the inflammatory responses stimulated by palmitate in C2C2 cells. The results showed that palmitate upregulated the mRNA expression and protein release of IL-6 and TNF-α cytokines in C2C12 cells, while pretreatment with curcumin was able to attenuate the effect of palmitate on inflammatory cytokines. The anti-inflammatory effect of curcumin was associated with the repression of phosphorylation of IKKα-IKKβ, and JNK. Palmitate also caused an increase in reactive oxygen species (ROS) level that curcumin abrogated it. Collectively, these findings suggest that curcumin may represent a promising therapy for prevention of inflammation in skeletal muscle cells.

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders affecting females of reproductive age. It has been associated with cardiometabolic disorders including diabetes mellitus and cardiovascular disorders, and increases the risk of developing fecundity pathologies including recurrent pregnancy loss (RPL) and infertility. C1q/tumor necrosis factor‐α‐related protein‐6 (CTRP6) is a novel adipokine involved in glucose and lipid metabolism, host inflammation, and organogenesis. In the present study, we aimed to determine the association of serum CTRP6 levels with some components of metabolic syndrome in PCOS patients (infertile PCOS [inf‐PCOS] and PCOS‐RPL). This case–control study included 120 PCOS patients (60 inf‐PCOS and 60 PCOS‐RPL) and 60 healthy controls. Serum high‐sensitivity C‐reactive protein (hs‐CRP) and homocysteine were measured using commercial kits, while adiponectin and CTRP6 levels were assessed using ELISA technique. Inf‐PCOS and PCOS‐RPL individuals had higher levels of serum CTRP6 than controls (546.15 ± 125.02 ng/ml and 534.04 ± 144.19 ng/ml vs. 440.16 ± 159.24 ng/ml; both p < .001). Moreover, serum adiponectin levels were significantly reduced, while fasting insulin, homeostasis model assessment of insulin resistance, free testosterone, and hs‐CRP levels were significantly elevated in PCOS group, when compared with controls. Furthermore, serum CTRP6 positively associated with body mass index in all subjects. It showed an inverse correlation with adiponectin in PCOS group and subgroups. However, it had a direct association with hs‐CRP in PCOS group and inf‐PCOS subgroup, but not PCOS‐RPL subgroup. These findings unravel a probable role of CTRP6 in PCOS pathogenesis, which poses a possibility to be a good diagnostic target. However, further investigation is needed.

Background Insulin resistance has a vital role in the pathophysiology of polycystic ovary syndrome (PCOS). Previous investigations have shown that some lipid ratios could be a simple clinical indicator of insulin resistance (IR) in some disorders and ethnicities. The present study was conducted to evaluate the correlation between triglyceride to HDL-cholesterol (TG/HDL-C), total cholesterol to HDL-cholesterol (TC/HDL-C), as well as fasting triglyceride-glucose (TyG) indices with IR (as measured by homeostasis model assessment of IR (HOMA-IR), quantitative insulin sensitivity check index (QUICKI) and fasting glucose to insulin ratio (FGIR)) among the Iranian women diagnosed with PCOS. Methods In the current study, a total of 305 women with PCOS were evaluated. TG/HDL-C, TC/HDL-C, and TyG indices were calculated. Fasting insulin level was measured using ELISA technique. IR was defined as a HOMA-IR value of ≥2.63, FG-IR value of < 8.25, and QUICKI value of < 0.33. Results The insulin-resistant (IR) and insulin-sensitive (IS) groups, established by the HOMA-IR, FG-IR, and QUICKI values were different in terms of TG/HDL-C, TC/HDL-C, and TyG indices. These indices were associated with IR even after adjusting for age and BMI. ROC curve analyses showed that TyG, TG/HDL-C, and TC/HDL-C strongly predicted HOMA-IR with area under the curve (AUC) of 0.639, 0.619, and 0.623, respectively (P < 0.05). Further, TC/HDL-C was a good predictor of FG-IR with AUC of 0.614 (P = 0.04). Conclusion TyG, TG/HDL-C, and TC/HDL-C indices might be good indicators of IR among Iranian women diagnosed with PCOS.

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