Downregulation of lncRNA ZFAS1 and upregulation of microRNA-129 repress endocrine disturbance, increase proliferation and inhibit apoptosis of ovarian granulosa cells in polycystic ovarian syndrome by downregulating HMGB1.

In polycystic ovary syndrome (PCOS), oxidative stress is implicated in the development of β-cell dysfunction. However, the role of mononuclear cell (MNC)-derived inflammation in this process is unc...

Pancreatic β-cell dysfunction in polycystic ovary syndrome: role of hyperglycemia-induced nuclear factor-κB activation and systemic inflammation

PCOS treatment should be based on pathophysiology. High-mobility-group-box-1 (HMGB1) was shown to increase in PCOS patients as a consequence of reduced cystic-fibrosis-transmembrane-conductance-reg...

HMGB1 is increased in adolescents with polycystic ovary syndrome (PCOS) and decreases after treatment with myo-inositol (MYO) in combination with alpha-lipoic acid (ALA).

Cells respond to stress by activating a variety of defense signaling pathways, including cell survival and cell death pathways. Although cell survival signaling helps the cell to recover from acute insults, cell death or senescence pathways induced by chronic insults can lead to unresolved pathologies. Arterial hypertension results from chronic physiological maladaptation against various stressors represented by abnormal circulating or local neurohormonal factors, mechanical stress, intracellular accumulation of toxic molecules, and dysfunctional organelles. Hypertension and aging share common mechanisms that mediate or prolong chronic cell stress, such as endoplasmic reticulum stress and accumulation of protein aggregates, oxidative stress, metabolic mitochondrial stress, DNA damage, stress-induced senescence, and proinflammatory processes. This review discusses common adaptive signaling mechanisms against these stresses including unfolded protein responses, antioxidant response element signaling, autophagy, mitophagy, and mitochondrial fission/fusion, STING (signaling effector stimulator of interferon genes)-mediated responses, and activation of pattern recognition receptors. The main molecular mechanisms by which the vasculature copes with hypertensive and aging stressors are presented and recent advancements in stress-adaptive signaling mechanisms as well as potential therapeutic targets are discussed.

Vascular Stress Signaling in Hypertension.

Regulatory network and targeted interventions for CCDC family in tumor pathogenesis.

High-mobility group box 1 (HMGB1) is newly discovered protein, which play a crucial role in the pathogenesis of systemic inflammation. Recent studies showed that HMGB1 is one of the important pathophysiological mechanisms in the occurrence and development of atherosclerosis. The purpose of the present study was to investigate the relationship between serum HMGB1 levels and endothelial function in patients with polycystic ovary syndrome (PCOS). Eighty newly diagnosed patients with PCOS and eighty normal women of similar age were selected. Metformin treatment (1,500 mg/day) was initiated in all patients for a period of consecutive 3 months. Serum HMGB1 levels were measured by ELISA. High resolution ultrasound was used to measure the brachial artery diameter at rest, after reactive hyperemia (flow-mediated arterial dilation, FMD) and after sublingual glyceryltrinitrate. Serum HMGB1 levels in PCOS were 24.87+/-14.93 ng/ml, which were significantly higher than that in controls (8.82+/-3.55 ng/ml, p<0.01). After 3 months treatment, serum HMGB1 levels decreased significantly (p<0.05). By dividing the distribution of HMGB1 levels into quartiles, serum HMGB1 levels were increased gradually with the increase of testosterone levels (p<0.05), whereas the FMD levels decreased (p<0.05). Multiple stepwise linear regression analysis showed that FMD (estimated coefficient beta=-0.69, p=0.005), testosterone (beta=0.31, p=0.045), TBARS (beta=0.69, p=0.012) and hs-CRP levels (beta=0.68, p=0.001) were significantly associated with HMGB1. The absolute changes in HMGB1 showed a positive correlation with the changes in testosterone (p<0.05) and negative correlation with the changes in FMD (p<0.05) in patients with PCOS during the course of metformin therapy. Serum HMGB1 levels are correlated with endothelial dysfunction in patients with PCOS. Our study suggests that HMGB1 may contribute to the early stage of atherosclerosis in patients with PCOS.

/pdf/serum-hmgb1-levels-and-its-association-with-endothelial-54fyd8x64i.pdf

Serum HMGB1 levels and its association with endothelial dysfunction in patients with polycystic ovary syndrome.

Asprosin, coiled-coil domain-containing 80(CCDC80) and angiopoietin-like 4(ANGPTL4) are newly discovered adipocytokine that affects glucose tolerance, insulin resistance and cardiovascular diseases. The goal of this study was to investigate if a relationship exists among asprosin, CCDC80 and ANGPTL4 and inflammatory bowel disease (IBD). Fifty subjects with newly diagnosed IBD and fifty healthy individuals were enrolled. Patients were treated with standard therapies for 3 months. Plasma asprosin, CCDC80 and ANGPTL4 levels were measured with enzyme-linked immunosorbent assay. High resolution ultrasound was used to measure brachial artery diameter at rest, after reactive hyperemia (flow-mediated dilation, FMD) and after sublingual glyceryltrinitrate. Compare with healthy individuals, plasma CCDC80,erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) levels and homeostasis model assessment of insulin resistance (HOMA-IR) were significantly higher (p < 0.05, respectively), whereas plasma asprosin, ,ANGPTL4 levels and FMD were significantly lower in both UC and CD patients(p <0.05). Plasma CCDC80 levels were significantly higher in patients with CD (p < 0.05), while plasma asprosin and ANGPTL4 levels were lower (pP < 0.05) as compared with those in patietns with UC. Standard therapies increased plasma asprosin, ANGPTL4 levels and FMD in both UC and CD (p<0.05),UC and CD patientswhile decreased plasma CCDC80, ESR, CRP levels and HOMA-IR (p<0.05). The changes in HOMA-IR and FMD were correlated with the changes in plasma asprosin, CCDC80 and ANGPTL4 levels over the study period (p<0.05). Plasma asprosin, CCDC80 and ANGPTL4 levels may be applied as a significant marker for early stage of insulin resistance and atherosclerosis in IBD, especially of CD.

/pdf/plasma-asprosin-ccdc80-and-angptl4-levels-are-associated-3zslrli8gy.pdf

Plasma asprosin, CCDC80 and ANGPTL4 levels are associated with metabolic and cardiovascular risk in patients with inflammatory bowel disease.

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Serum HMGB1 levels and its association with endothelial dysfunction in patients with polycystic ovary syndrome.

Plasma asprosin, CCDC80 and ANGPTL4 levels are associated with metabolic and cardiovascular risk in patients with inflammatory bowel disease.