The endocannabinoid system is found in most, if not all, mammalian organs and is involved in a variety of physiological functions, ranging from the control of synaptic plasticity in the brain to the modulation of smooth muscle motility in the gastrointestinal tract. This signaling complex consists of G protein-coupled cannabinoid receptors, endogenous ligands for those receptors (endocannabinoids) and enzymes/transporters responsible for the formation and deactivation of these ligands. There are two subtypes of cannabinoid receptors, CB1 and CB2, and two major endocannabinoids, arachidonoylethanolamide (anandamide) and 2-arachidonoyl-sn-glycerol (2-AG), which are produced upon demand through cleavage of distinct phospholipid precursors. All molecular components of the endocannabinoid system are represented in the adipose organ, where endocannabinoid signals are thought to regulate critical homeostatic processes, including adipogenesis, lipogenesis and thermogenesis. Importantly, obesity was found to be associated with excess endocannabinoid activity in visceral fat depots, and the therapeutic potential of normalizing such activity by blocking CB1 receptors has been the focus of substantial preclinical and clinical research.  https://www.selleckchem.com/products/opicapone.html  Results have been mixed thus far, mostly owing to the emergence of psychiatric side effects rooted in the protective functions served by brain endocannabinoids in mood and affect regulation. Further studies about the roles played by the endocannabinoid system in the adipose organ will offer new insights into the pathogenesis of obesity and might help identify new ways to leverage this signaling complex for therapeutic benefit.Obesity is a global public health problem that results in chronic pathologies such as diabetes, cardiovascular diseases, and cancer. The treatment approach based on energy restriction and promotion of physical activity is ineffective in the long term. Due to the high prevalence of this pathology, complementary treatments such as brown adipose tissue activation (BAT) and white adipose tissue browning (WAT) have been proposed. Dietary polyphenols are plant secondary metabolites that can stimulate browning and thermogenesis of adipose tissue. They have also been shown to prevent body weight gain, and decrease systemic inflammation produced by high-fat diets. Ingested dietary polyphenols that reach the colon are metabolized by the gut microbiota (GM), regulating its composition and generating a great array of metabolites. GM is involved in the production of short chain fatty acids and secondary bile salts that regulate energetic metabolism. The alteration in the composition of GM observed in metabolic diseases such as obesity and type 2 diabetes can be attenuated by polyphenols. Recent studies support the hypothesis that GM would mediate WAT browning and BAT thermogenesis activation induced by polyphenol administration. Together, these results indicate that GM in the presence of polyphenols plays a fundamental role in the control of obesity possible through BAT activation.
  The impact of an increased body mass index (BMI) on outcomes of neoadjuvant chemotherapy (NACT) in breast cancer remains controversial. The purpose of this study was to analyze the impact of BMI on pathological complete response (pCR) rates for operable breast cancer after NACT.
 
  We searched Medline, Embase, and Web of Science database for observational studies and randomized controlled trials that reported the association of BMI with pCR after NACT. We performed a meta-analysis to assess the impact of BMI on pCR rate.
 
  We identified 13 studies including a total of 18,702 women with operable breast cancer who underwent NACT. Two studies were pooled analyses of prospective clinical trials (10,669 patients); the rest were case-control studies (8033 patients). All studies provided data of two BMI groups (BMI < 25 vs. BMI ≥ 25). Pooled analyses demonstrated that overweight/obese women were less likely to achieve pCR after NACT as compared to under-/normal weight women (odds ratio (OR) = 0.80; 95% confidence interval (CI) 0.68-0.93). Eleven studies provided data of three BMI groups (BMI < 25, 25 ≤ BMI < 30, BMI ≥ 30). Based on pooled analyses, both overweight and obese groups were less likely to achieve pCR with NACT as compared to under-/normal weight group, (OR = 0.77, 95% CI 0.65-0.93 and OR = 0.68, 95% CI 0.61-0.77, respectively).
 
  Overweight and obese breast cancer patients had a lower pCR rate with NACT compared to patients with under-/normal weight. Further prospective studies may help confirm this finding and investigate possible mechanisms.
 Overweight and obese breast cancer patients had a lower pCR rate with NACT compared to patients with under-/normal weight. Further prospective studies may help confirm this finding and investigate possible mechanisms.
  The optimal duration of endocrine therapy for patients with hormonereceptor-positive (HR-positive) breast cancer is still unclear. This meta-analysis aims to determine the optimal duration of endocrine therapy with extended aromatase inhibitors(AI) for postmenopausal patients with HR-positive early breast cancer who have finished 5years of endocrine therapy.
 
  Eligible randomized controlled trials were classified into three categories according to the whole duration of endocrine therapy (10years versus 5years, 7-8years versus 5years, and 10years versus 7-8years). For each category, hazard ratio (HR) for disease-free survival (DFS) and overall survival (OS), and risk ratio (RR) for the incidence of adverse events were pooled.
 
  Altogether 9 RCTs enrolling a total of 22,313 postmenopausal women with HR-positive breast cancer were included. Pooled data showed an improvement in DFS when extending endocrine therapy from 5 to 7-8years (HR = 0.79 [0.69, 0.91]), specifically among those who had been treated with onith AI for 5 years, with tumors that are node-negative, ER+/PR- or ER-/PR+, and  less then  2 cm in size do not need to receive extended AI therapy. For those who have been treated with only tamoxifen or sequential tamoxifen followed by an AI for a total of 5 years, with tumors that are node-positive, ER+/PR+ or ≥ 2 cm in size, 2-3 years of extended AI is necessary and maybe enough.