Observational studies suggest better clinical outcomes following critical illness in patients with overweight and obesity (obesity paradox). An understanding of the morphologic, physiologic and metabolic changes in adipose tissue in critical illness may provide an explanation. Recent studies have demonstrated the transformation of white to brown-like adipocytes due to the "browning process," which has been of interest as a potential novel therapy in obesity during the last decade. The characteristics of the browning of white adipose tissue (WAT) include the appearance of smaller, multilocular adipocytes, increased UCP1 mRNA expression, mitochondrial density and respiratory capacity. These changes have been identified in some critical illnesses, which specifically refers to burns, sepsis and cancer cachexia in this study. The pathophysiological nature of WAT browning, underlying mechanisms, main regulators and potential benefits and harms of this process are interesting new areas that warrants further investigations. In this review, we discuss emerging scientific discipline of adipose tissue physiology in metabolic stress, available data, gaps of knowledge and future perspectives. Future investigations in this field may provide insights into the underlying mechanisms and clinical aspects of browning that may further our understanding of the proposed obesity paradox following critical illness, which may in turn open up opportunities for novel therapies to save lives and improve recovery.

Metal-organic frameworks, such as MIL-100, have been recently introduced as promising drug carriers due to their notable characteristics such as stability, biocompatibility and owning large porosity which may admit a broad range of drugs with different molecular sizes. In this study, we firstly proposed an accessible top-down approach using ultrasound method to prepare nanoMIL-100 and secondly, evaluated its potentials as an anticancer nanocarrier. This is the first report that docetaxel (DTX) as a highly hydrophobic anticancer drug was encapsulated in nanoMIL-100 with the drug payload of 57.2 wt%. Characterizations of the prepared nanoMIL-100 and DTX-loaded nanoMIL-100 were performed by PXRD, FT-IR, N adsorption, DLS and FE-SEM. Moreover, the drug loading and release processes were quantified by HPLC. The in vitro release of DTX from the prepared nanocarrier was investigated in two pH values, 7.4 and 5.5. The toxic effect of DTX-loaded nanoMIL-100 was examined on human breast cancer cell line, MCF-7, and a significant decrease was observed in IC value (0.198 μg/mL) at the first 24 h in comparison with the free drug (4.9908 μg/mL). This nanocarrier may, thus offer promising potentials as a novel cytotoxic drug delivery system.

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Oxidative stress plays a fundamental role in the development and progression of nonalcoholic fatty liver disease (NAFLD). This study aimed to investigate the effects of a calorie-restricted (CR) diet on oxidative/anti-oxidative status in patients with NAFLD and the potential mediating role of fibroblast growth factor 21 (FGF-21) in this regard. This randomized, controlled clinical trial was carried out on sixty patients with NAFLD aged 20 to 60 years with body mass index (BMI) ranging from 25 to 35 kg/m2. Participants were randomly assigned to either the CR diet group (received a prescribed low-calorie diet for twelve weeks, n = 30) or the control group (n = 30). Fasting blood samples, anthropometric measurements, dietary intake, and physical activity data were collected for all participants at baseline and at the end of the trial. Significant reductions in weight, BMI, waist circumference, and serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were observed in the CR diet group compared to the control group (all p< 0.05). Liver steatosis grade, serum levels of malondialdehyde (MDA), total antioxidant capacity (TAC), and FGF-21, as well as erythrocyte superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities did not show significant changes in the CR group when compared to the controls at the end of the study (p > 0.05). CR diet with moderate weight loss has some favorable effects on NAFLD but was not able to modify oxidative/anti-oxidative status in these patients. Future studies are warranted to target the effects of long-term interventions with a greater weight loss in this patient population.

Mannosylation of nanovaccine is an appropriate strategy for targeting the mannose receptors on DCs. Here, HBsAg and mannose loaded on the surface of iron oxide nanoparticles to increases HBsAg vaccine potency. Nanoparticles are made by co-precipitation method and bonded to the HBsAg and mannose by chemical bonding. The physicochemical properties of nano-vaccines, their toxicity and antigenicity were determined. The synthesized nano-vaccine showed spherical shape with a mean particle size of 60 nm, a zeta potential of À44 mV, an antigen-binding efficiency of around 100% and for mannose 78%. In vitro release of nanoparticles exhibited about 30% at the first day and about 60% until the third day. SDSPAGE analysis confirmed structural integrity of HBsAg loaded on nanoparticles. The HBsAg-loaded LCMNP and MLCMNP nanoparticles had no toxic effects on HEK293 cell line. The quantification of the intracellular Fe by ICP-OES as a criterion of nano-vaccine uptake revealed mannose intensify uptake of MLCMNP. In addition, mannose in the structure of MLCMNP improved IL-6, TNF-a and IFN-c (>16 fold) cytokines genes expression by macrophage/dendritic cells after exposure in 12 h. Immunization of experimental mice (subcutaneously, two times with 2-week intervals) with 5 mg of HBsAg loaded on MLCMNP nanoparticles increased specific total IgG and IgG2a/IgG1 ratio. In addition, TNF-a, IL-12, IL-2 and IL-4 cytokines in mannosylated nano-vaccine increased versus nano-vaccine group while lymphocyte proliferation and IFN-c responses in the targeted nano-vaccine group show a tiny increase versus the nano-vaccine group. The results show that mannosylated nano-vaccine promotes higher level of cellular and humoural immune responses against HBsAg nano-vaccine.