Chronic inflammation drives many obesity-associated conditions including atherosclerosis. GlycA, a marker of systemic inflammation with lower intra-individual variability than high sensitivity C-reactive protein, is independently associated with incident cardiovascular events and mortality. Although GlycA is elevated in obesity, correlations with anthropometric measures are modest and the effect of body weight loss on GlycA is untested. Obese (body mass index [BMI] 44.6 ± 6.6 kg/m ), non-diabetic women (33.7 ± 8.2 years) undergoing Roux-en-Y gastric bypass (n = 23) or sleeve gastrectomy (n = 31) were prospectively studied at baseline, 6 and 12 months postprocedure. Women with normal BMI (n = 14) served as controls. Bariatric surgery significantly reduced GlycA by 6 months (451 ± 47 μmol/L vs. 383 ± 50 μmol/L; P < 0.001) with further reduction at 12 months (348 ± 41 μmol/L; P < 0.001) and no difference between procedures. At 12 months, despite 41% of surgical subjects maintaining BMI >30 kg/m , GlycA levels did not differ between surgical and control subjects (P = 0.13). Increased high density lipoprotein particle size was strongly associated with reduced GlycA (r = -0.49; P < 0.001) and was found to mediate up to 43% of its body weight-loss-associated fall. This is the first study to demonstrate that surgical body weight loss markedly reduces levels of GlycA.
SG and RYGB produce similar weight loss, but contrasting effects on CEC. These findings may be relevant in discussions about the type of procedure that is most appropriate for a particular obese patient. Further study of the mechanisms underlying these changes may lead to improved understanding of the factors governing CEC and potential therapeutic interventions to maximally reduce cardiovascular disease risk in both obese and nonobese patients.
Cancer stem cells (CSCs), a crucial cancer cell subpopulation, possess stemness phenotypic characteristics. Cucurbitacin B (CuB), a tetracyclic triterpenoid isolated from Cucurbitaceae, exerts widely pharmacological activities in many diseases. The aim of this study was to enrich, identify liver CSCs and investigate antitumor effects of CuB as well as explore the underlying molecular mechanisms in these liver CSCs. HepG2 cell lines were used for the enrichment of liver CSCs by serum-free medium culture and magnetic-activated cell sorting. The CSC characteristics were analyzed by immunofluorescent staining, sphere-forming, western blot and xenograft tumorigenicity assay. CuB' antitumor effects and underlying molecular mechanism were measured by cell counting kit-8, colony formation, sphere-forming, cell cycle, xenograft and western blot assay. Our results showed that we could enrich 97.29% CD133+ HepG2 cells, which possessed CSC characteristics including re-renewal capacity, proliferative ability, sorafenib resistance, overexpressed stemness-related molecules and enhanced tumorigenic potential. Furthermore, we also found that CuB inhibited cell viability, sphere formation, colony formation and arrested cell cycle at G2/M phase as well as sensitized CD133+ HepG2 cells to sorafenib in vitro and in vivo. Western blot assay indicated that CuB inhibited expression levels of cyclin B1, CDK1, CD133, p-JAK2 and p-STAT3. In conclusion, our findings indicated that CuB could exhibit antitumor effects on CD133+ HepG2 CSCs by inhibiting the Janus kinase 2/signal transducers and activators of transcription-3 signaling pathway, expanding basic and preclinical investigations on liver CSCs.
Background-Lipoprotein insulin resistance (LPIR) is a composite biomarker representative of atherogenic dyslipidemia characteristic of early insulin resistance. It is elevated in obesity and may provide information not captured in hemoglobin A1c (A1C) and homeostatic model assessment for insulin resistance (HOMA-IR). While bariatric surgery reduces diabetes incidence and resolves metabolic syndrome, the effect of bariatric surgery on LPIR is untested.Objectives-We sought to assess the effects of Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) on LPIR in non-diabetic women with obesity.Settings-Non-smoking, non-diabetic, premenopausal Hispanic women, age ≥18 years, undergoing RYGB or SG at Bellevue Hospital (New York, NY) were recruited for a prospective observational study.Methods-Anthropometric measures and blood sampling were performed preoperatively and at six, and 12 months postoperatively. LPIR was measured by Nuclear Magnetic Resonance (NMR) spectroscopy.Results-Among 53 women (RYGB, n=22; SG, n=31), mean age was 32±7 years and body mass index (BMI) 44.1±6.4 kg/m 2 . LPIR was reduced by 35±4% and 46±4% at six and 12 months after surgery, respectively, with no difference by procedure. Twenty-seven of 53 subjects met International Diabetes Federation (IDF) criteria for metabolic syndrome preoperatively and had concomitant higher HOMA-IR, A1C, non-high density lipoprotein-cholesterol (nonHDL-C) and *
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