Maciasblake0363
Studies have established that congenital cataract is the major cause of blindness in children across the globe. The β-crystallin protein family is the richest and most soluble structural protein in the lens. Their solubility and stability are essential in maintaining lens transparency. In this study, we identified a novel βB2 mutation W151R in a rare progressive cortical congenital cataract family and explored its pathogenesis using purified protein and mutant related cataract-cell models. Due to its low solubility and poor structural stability, the βB2 W151R mutation was prone to aggregation. Moreover, the W151R mutation enhanced the exposure of the hydrophobic side chains in the fourth Greek Key motif, which were readily degraded by trypsin. However, upon the administration of lanosterol, the negative effect of the W151R mutation was reversed. Therefore, lanosterol is a potential therapeutic option for cataracts.To adapt to tumoral environment conditions or even to escape chemotherapy, cells rapidly reprogram their metabolism to handle adversities and survive. Given the rapid rise of studies uncovering novel insights and therapeutic opportunities based on the role of mitochondria in tumor metabolic programing and therapeutics, this review summarizes most significant developments in the field. Taking in mind the key role of mitochondria on carcinogenesis and tumor progression due to their involvement on tumor plasticity, metabolic remodeling, and signaling re-wiring, those organelles are also potential therapeutic targets. Among other topics, we address the recent data intersecting mitochondria as of prognostic value and staging in cancer, by mitochondrial DNA (mtDNA) determination, and current inhibitors developments targeting mtDNA, OXPHOS machinery and metabolic pathways. We contribute for a holistic view of the role of mitochondria metabolism and directed therapeutics to understand tumor metabolism, to circumvent therapy resistance, and to control tumor development.
Excess visceral fat (VF) or high body mass index (BMI) is risk factors for severe COVID-19. The receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is expressed at higher levels in the VF than in the subcutaneous fat (SCF) of obese patients.
To show that visceral fat accumulation better predicts severity of COVID-19 outcome compared to either SCF amounts or BMI.
We selected patients with symptomatic COVID-19 and a computed tomography (CT) scan. Severe COVID-19 was defined as requirement for mechanical ventilation or death. Fat depots were quantified on abdominal CT scan slices and the measurements were correlated with the clinical outcomes. ACE 2 mRNA levels were quantified in fat depots of a separate group of non-COVID-19 subjects using RT-qPCR.
Among 165 patients with a mean BMI of 26.1 ± 5.4 kg/m
, VF was associated with severe COVID-19 (p = 0.022) and SCF was not (p = 0.640). Subcutaneous fat was not different in patients with mild or severe COVID-19 and the SCF/VF ratio was lower in patients with severe COVID-19 (p = 0.010). The best predictive value for severe COVID-19 was found for a VF area ≥128.5 cm
(ROC curve), which was independently associated with COVID-19 severity (p < 0.001). In an exploratory analysis, ACE 2 mRNA positively correlated with BMI in VF but not in SCF of non-COVID-19 patients (r
= 0.27 vs 0.0008).
Severe forms of COVID-19 are associated with high visceral adiposity in European adults. On the basis of an exploratory analysis ACE 2 in the visceral fat may be a trigger for the cytokine storm, and this needs to be clarified by future studies.
Severe forms of COVID-19 are associated with high visceral adiposity in European adults. On the basis of an exploratory analysis ACE 2 in the visceral fat may be a trigger for the cytokine storm, and this needs to be clarified by future studies.
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. Whether moderate alcohol consumption plays a role for progression of NAFLD is disputed. Moreover, it is not known which tool is ideal for assessment of alcohol consumption in NAFLD. This study aimed to evaluate if moderate alcohol consumption assessed with different methods, including the biological marker phosphatidylethanol (PEth), is associated with advanced fibrosis in NAFLD.
We conducted a cross-sectional study of patients with biopsy-proven NAFLD. All participants were clinically evaluated with medical history, blood tests, and anthropometric measurements. Alcohol consumption was assessed using PEth in blood, the questionnaire AUDIT-C, and clinical interview.
86 patients were included of which 17% had advanced fibrosis. All participants reported alcohol consumption < 140 g/week. Average weekly alcohol consumption was higher in the group with advanced fibrosis. Moderate alcohol consumption, independentlcating increased risk for advanced fibrosis in NAFLD. Patients with T2DM consuming moderate amounts of alcohol had the highest risk of advanced fibrosis, indicating a synergistic effect of insulin resistance and alcohol on the histopathological progression of NAFLD.Poly (lactic acid)/lignin nanocomposites (PLA/Lig-Np) containing cinnamaldehyde (Ci) were obtained by a combination of melt extrusion and supercritical impregnation process. In this work, Ci impregnation tests were carried out in a high-pressure cell at 40 °C for 3 h using 12 MPa and 1 MPa min-1 of depressurization rate, obtaining impregnation yields ranging from 5.7 to 10.8% w/w. Thermal, mechanical and colorimetric properties of the developed films were affected by the incorporation of lignin nanoparticles and the active compound, obtaining biodegradable plastic materials with a strong UV-light barrier property compared to PLA films. GSK2879552 purchase In addition, disintegrability tests under composting conditions confirmed the biodegradable character of nanocomposites developed. On day 23, a disintegration percentage greater than 90% was determined for all bionanocomposites. Finally, to establish the possible toxicity effect of the nanocomposites obtained, studies in vivo were performed in normal rats. Toxicity studies showed normal blood parameters after a single dose of nanocomposites.