Genetic Variation in 11β-Hydroxysteroid Dehydrogenase Type 1 Predicts Adrenal Hyperandrogenism among Lean Women with Polycystic Ovary Syndrome

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Effects of Prunus cerasus L. Seeds and Juice on Liver Steatosis in an Animal Model of Diet-Induced Obesity

The accumulation of adipose tissue increases the risk of several diseases. The fruits-intake, containing phytochemicals, is inversely correlated with their development. This study evaluated the effects of anthocyanin-rich tart cherries in diet-induced obese (DIO) rats. DIO rats were exposed to a high-fat diet with the supplementation of tart cherry seeds powder (DS) and seed powder plus juice (DJS). After 17 weeks, the DIO rats showed an increase of body weight, glycaemia, insulin, and systolic blood pressure. In the DS and DJS groups, there was a decrease of systolic blood pressure, glycaemia, triglycerides, and thiobarbituric reactive substances in the serum. In the DJS rats, computed tomography revealed a decrease in the spleen-to-liver attenuation ratio. Indeed, sections of the DIO rats presented hepatic injury characterized by steatosis, which was lower in the supplemented groups. In the liver of the DIO compared with rats fed with a standard diet (CHOW), a down-regulation of the GRP94 protein expression and a reduction of LC3- II/LC3-I ratio were found, indicating endoplasmic reticulum stress and impaired autophagy flux. Interestingly, tart cherry supplementation enhanced both unfolded protein response (UPR) and autophagy. This study suggests that tart cherry supplementation, although it did not reduce body weight in the DIO rats, prevented its related risk factors and liver steatosis

Effects of Prunus cerasus L. Seeds and Juice on Liver Steatosis in an Animal Model of Diet-Induced Obesity

The accumulation of adipose tissue increases the risk of several diseases. The fruits-intake, containing phytochemicals, is inversely correlated with their development. This study evaluated the effects of anthocyanin-rich tart cherries in diet-induced obese (DIO) rats. DIO rats were exposed to a high-fat diet with the supplementation of tart cherry seeds powder (DS) and seed powder plus juice (DJS). After 17 weeks, the DIO rats showed an increase of body weight, glycaemia, insulin, and systolic blood pressure. In the DS and DJS groups, there was a decrease of systolic blood pressure, glycaemia, triglycerides, and thiobarbituric reactive substances in the serum. In the DJS rats, computed tomography revealed a decrease in the spleen-to-liver attenuation ratio. Indeed, sections of the DIO rats presented hepatic injury characterized by steatosis, which was lower in the supplemented groups. In the liver of the DIO compared with rats fed with a standard diet (CHOW), a down-regulation of the GRP94 protein expression and a reduction of LC3- II/LC3-I ratio were found, indicating endoplasmic reticulum stress and impaired autophagy flux. Interestingly, tart cherry supplementation enhanced both unfolded protein response (UPR) and autophagy. This study suggests that tart cherry supplementation, although it did not reduce body weight in the DIO rats, prevented its related risk factors and liver steatosis

Tissue-specific dysregulation of 11\u3b2-hydroxysteroid dehydrogenase type 1 in overweight/obese women with polycystic ovary syndrome compared with weight-matched controls

CONTEXT:Abnormal cortisol metabolism in polycystic ovary syndrome (PCOS) has been invoked as a cause of secondary activation of the hypothalamic-pituitary-adrenal axis and hence androgen excess. However, this is based on urinary excretion of cortisol metabolites, which cannot detect tissue-specific changes in metabolism and may be confounded by obesity. OBJECTIVE:To assess cortisol clearance and whole-body and tissue-specific activities of 11\u3b2-hydroxysteroid dehydrogenase type 1 (11\u3b2-HSD1 (HSD11B1)) in PCOS. DESIGN:Case-control study. SETTING:Medical center. PATIENTS:A total of 20 overweight-obese unmedicated Caucasian women with PCOS, aged 18-45 years, and 20 Caucasian controls matched for age, BMI, body fat distribution, and HSD11B1 genotypes (rs846910 and rs12086634). MAIN OUTCOME MEASURES:Cortisol metabolites were measured in 24\u200ah urine. During steady-state 9,11,12,12-[(2)H]4-cortisol infusion, cortisol clearance was calculated and whole-body HSD11B1 activity was assessed as the rate of appearance of 9,12,12-(2)H3-cortisol (d3-cortisol). Hepatic HSD11B1 activity was quantified as the generation of plasma cortisol following an oral dose of cortisone. Subcutaneous adipose HSD11B1 activity and HSD11B1 mRNA were measured, ex vivo, in biopsies. RESULTS:Urinary cortisol metabolite excretion, deuterated cortisol clearance, and the rate of appearance of d3-cortisol did not differ between patients with PCOS and controls. However, hepatic HSD11B1 conversion of oral cortisone to cortisol was impaired (P<0.05), whereas subcutaneous abdominal adipose tissue HSD11B1 mRNA levels and activity were increased (P<0.05) in women with PCOS when compared with controls. CONCLUSIONS:Tissue-specific dysregulation of HSD11B1 is a feature of PCOS, over and above obesity, whereas increased clearance of cortisol may result from obesity rather than PCOS

Dynamic FDG PET/CT on bladder paraganglioma: A case report

Paraganglioma (PGL) is characterized by equivocal clinical manifestations and arriving to a suspicion might be challenging. Nevertheless, diagnostic imaging and nuclear medicine are a fundamental part of the diagnosis and management of this particular neuroendocrine tumor (NET). We herein report a rare case of bladder paraganglioma with unusual onset and typical PET/CT characteristics that led to its recognition

Unveiling the Molecular Mechanisms Driving the Capsaicin-Induced Immunomodulatory Effects on PD-L1 Expression in Bladder and Renal Cancer Cell Lines

The blockade of the PD-L1/PD-1 immune checkpoint has promising efficacy in cancer treatment. However, few patients with bladder cancer (BC) or renal cell carcinoma (RCC) respond to this approach. Thus, it is important to implement a strategy to stimulate the immune anti-tumor response. In this scenario, our study evaluated the effects of a low capsaicin (CPS) dose in BC and RCC cell lines. Western blot, qRT-PCR and confocal microscopy were used to assess PD-L1 mRNA and protein expression. Alterations to the cellular oxidative status and changes to the antioxidant NME4 levels, mRNA modulation of cytokines, growth factors, transcriptional factors and oncogene, and the activation of Stat1/Stat3 pathways were examined using Western blot, cytofluorimetry and qRT-PCR profiling assays. In BC, CPS triggers an altered stress oxidative-mediated DNA double-strand break response and increases the PD-L1 expression. On the contrary, in RCC, CPS, by stimulating an efficient DNA damage repair response, thus triggering protein carbonylation, reduces the PD-L1 expression. Overall, our results show that CPS mediates a multi-faceted approach. In modulating PD-L1 expression, there is a rationale for CPS exploitation as a stimulus that increases BC cells&rsquo; response to immunotherapy or as an immune adjuvant to improve the efficacy of the conventional therapy in RCC patients

The Prognostic Value of the Circulating Tumor Cell-Based Four mRNA Scoring System: A New Non-Invasive Setting for the Management of Bladder Cancer

Bladder cancer (BC) is one of the most expensive lifetime cancers to treat because of the high recurrence rate, repeated surgeries, and long-term cystoscopy monitoring and treatment. The lack of an accurate classification system predicting the risk of recurrence or progression leads to the search for new biomarkers and strategies. Our pilot study aimed to identify a prognostic gene signature in circulating tumor cells (CTCs) isolated by ScreenCell devices from muscle invasive and non-muscle invasive BC patients. Through the PubMed database and Cancer Genome Atlas dataset, a panel of 15 genes modulated in BC with respect to normal tissues was selected. Their expression was evaluated in CTCs and thanks to the univariate and multivariate Cox regression analysis, EGFR, TRPM4, TWIST1, and ZEB1 were recognized as prognostic biomarkers. Thereafter, by using the risk score model, we demonstrated that this 4-gene signature significantly grouped patients into high- and low-risk in terms of recurrence free survival (HR = 2.704, 95% CI = 1.010–7.313, Log-rank p < 0.050). Overall, we identified a new prognostic signature that directly impacted the prediction of recurrence, improving the choice of the best treatment for BC patients