BACKGROUND Irisin, a myokine released from skeletal muscle following exercise, has been shown to affect the proliferation of some cancer cells and chemosensitivity of anticancer drugs like doxorubicin (DOX). However, the effects of irisin on chemosensitivity in pancreatic cancer (PC) cells have not been studied. MATERIAL AND METHODS In this study, the effects of irisin co-treatment with DOX or gemcitabine (GEM) on MIA PaCa-2, BxPC-3 PC cells, and H9c2 cardiomyocytes were investigated. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, flow cytometry, and TUNEL (TdT-mediated dUTP nick-end labeling) assays were conducted to evaluate cytotoxicity induced by DOX or GEM. Fluorescence microscopy and flow cytometry experiments were performed to assess the intracellular accumulation of DOX. Cellular levels of apoptosis-related protein expression and protein phosphorylation were determined by Western blot analyses. RESULTS The results showed that irisin can increase the chemosensitivity of PC cells to DOX or GEM. The analyses of apoptosis indicated that irisin enhances DOX-induced cellular apoptosis by increasing the expression of cleaved PARP (poly ADP-ribose polymerase) and cleaved caspase-3, and reducing the expression of B cell lymphoma/lewkmia-2 (BCL-2) and B cell lymphoma-extra large (BCL-xL) in PC cells but not in H9c2 cells. Irisin attenuated serine/threonine kinase AKT (protein kinase B/PKB) phosphorylation and inhibited the activation of nuclear factor kappaB (NF-kappaB) signaling in PC cells. CONCLUSIONS Irisin can potentiate the cytotoxicity of doxorubicin in PC cells without increasing cardiotoxicity, possibly through inactivating the PI3K/AKT/NF-kappaB signaling pathway.

Significant differences in salivary microbiota communities between polycystic ovary syndrome (PCOS) patients and healthy controls have been reported, and interestingly, some salivary microbiota exhibit diurnal oscillation in healthy people. However, whether the diurnal oscillation of salivary microbiota is present in PCOS patients is unknown. In this study, we describe the differences in the saliva microbiome between the PCOS group and the control group at different time points over 24 h. 16S rRNA gene amplicon sequencing was performed on salivary and fecal samples from 10 PCOS patients and 10 healthy controls, and salivary samples were collected at 6-h intervals over 24 h (Zeitgeber (ZT)0, ZT6, ZT12, and ZT18). Among the salivary samples, those from the PCOS group showed significant differences from those of the control group at each time point. Differences were evident in taxa level and metabolic pathways. Interestingly, we found that PCOS disrupted the diurnal rhythm of the salivary microbiota abundance, as determined in the group of healthy women. In addition, no similar changes were found in PCOS patients and controls between the oral and fecal microbiota, including differential microbiota at the phylum level. In this study, significant differences in the composition of the salivary microbiota between PCOS and healthy women were detected at different time points. We also showed that the diurnal rhythm of relative abundance of the salivary microbiota was disrupted in patients with PCOS, which might be related to development of oral-related diseases and systematic metabolic disorders.

Li Y, et al. Diabetes Metab J. 2020 Jan;44:e40. https://doi.org/10.4093/dmj.2019.0151

Zhu Y, et al. Diabetes Metab J. 2019 Jan;43:e61. https://doi.org/10.4093/dmj.2019.0007

The prevalence of celiac disease autoimmunity or tissue transglutaminase autoantibodies (TGA) amongst patients with type 1 diabetes (T1D) and autoimmune thyroid disease (AITD) in the Chinese population remains unknown. This study examined the rate of celiac disease autoimmunity amongst patients with T1D and AITD in the Chinese population. The study included 178 patients with type 1 diabetes and 119 with AITD where 36 had both T1D and AITD, classified as autoimmune polyglandular syndrome type 3 variant (APS3v). The study also included 145 patients with type 2 diabetes (T2D), 97 patients with non-autoimmune thyroid disease (NAITD), and 102 healthy controls. Serum islet autoantibodies, thyroid autoantibodies and TGA were measured by radioimmunoassay. TGA positivity was found in 22% of patients with either type 1 diabetes or AITD, much higher than that in patients with T2D (3.4%; p< 0.0001) or NAITD (3.1%; P < 0.0001) or healthy controls (1%; p<0.0001). The patients with APS3v having both T1D and AITD were 36% positive for TGA, significantly higher than patients with T1D alone (p = 0.040) or with AITD alone (p = 0.017). T1D and AITD were found to have a 20% and 30% frequency of overlap respectively at diagnosis. In conclusion, TGA positivity was high in the Chinese population having existing T1D and/or AITD, and even higher when both diseases were present. Routine TGA screening in patients with T1D or AITD will be important to early identify celiac disease autoimmunity for better clinical care of patients.