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  • Vincent posted an update 1 year, 1 month ago

    In summary, our results reveal a novel miR-522/p63 axis in cell migration and thus suggest a potential strategy for therapeutic treatment of cancer metastasis.Aberrant expression of mitochondrial proteins impairs cardiac function and causes heart disease. The mechanism of regulation of mitochondria encoded protein expression during cardiac disease, however, remains underexplored. Here, we show that multiple pathogenic cardiac stressors induce the expression of miR-574 guide and passenger strands (miR-574-5p/3p) in both humans and mice. miR-574 knockout mice exhibit severe cardiac disorder under different pathogenic cardiac stresses while miR-574-5p/3p mimics that are delivered systematically using nanoparticles reduce cardiac pathogenesis under disease insults. Transcriptomic analysis of miR-574-null hearts uncovers family with sequence similarity 210 member A (FAM210A) as a common target mRNA of miR-574-5p and miR-574-3p. The interactome capture analysis suggests that FAM210A interacts with mitochondrial translation elongation factor EF-Tu. Manipulating miR-574-5p/3p or FAM210A expression changes the protein expression of mitochondrial-encoded electron transport chain (ETC) genes but not nuclear-encoded mitochondrial ETC genes in both human AC16 cardiomyocyte cells and miR-574-null murine hearts. Together, we discovered that miR-574 regulates FAM210A expression and modulates mitochondrial-encoded protein expression, which may influence cardiac remodeling in heart failure.Melanocortin-4 receptor (MC4R) gene plays a key role in the regulation of body weight and energy homeostasis. This study aims to evaluate the association of single nucleotide polymorphisms (SNPs) of the MC4R gene with live body weight and hormonal assays in two breeds of sheep that differ in productive performance, Awassi and Arabi. All known coding sequences of the MC4R gene were covered in this study. DNA samples from 150 animals (Awassi and Arabi breed) were genotyped by PCR-single-strand conformation polymorphism (PCR-SSCP) to assess their pattern of genetic variation. Concerning exon 1, clear heterogeneity was detected with three different SSCP-banding patterns. The sequencing reactions confirmed these variations by detecting the presence of the two novel SNPs, 107G/C and 138A/C, and three genotypes, GC, AC and AA. The 107G/C SNP was detected in GC genotype, while the 138A/C was detected on both GC and AC genotypes. The other SSCP-banding pattern (AA genotype) did not show any detectable unique variation. Both SNPs were closely and strongly linked in both breeds (D’ and r2 values were 1.00), which signifies that both loci were co-inherited as one unit. Association analysis indicated that both breeds with GC/AC haplotype showed higher live body weight (37.250 ± 0.790) relative to the GG/AA (30.244 ± 0.968) and CC/CC (47.231 ± 1.230) haplotypes (p .05) with the measured traits. In conclusion, the two novel SNPs (107G/C and 138 A/C) were highly associated with live body weight in both breeds. Haplotype analysis confirmed that these two novel SNPs were in strong linkage disequilibrium (LD) and could be used as genetic markers for sheep phenotypic trait improvement.This communication reports the beneficial effects of co-gasification of biomass and residual oil to produce syngas. In this regard, various blends of glucose (a biomass surrogate) to vacuum gas oil (VGO) have been employed to investigate the synergic effects on the gasification process. The non-isothermal co-gasification experiments were conducted in a thermogravimetric analyzer at different heating rates and gasifying agents. The analysis showed that the co-gasification rate increased with the increase of glucose content in the feedstock. The presence of the oxygen in the biomass molecules helped the overall gasification process. The maximum gasification rate of 42.70 wt/min (DTGmax ) was observed with 25 wt% glucose containing sample. The use of gasifying agents appeared to have some influence, especially during high temperature gasification of the glucose-VGO blends. At a same gasification temperature, the co-gasification rate of glucose-VGO blends were found to be 125.7 wt/min and 98.59 wt%/min for N2 and CO2 , respectively. The kinetics of the co-gasification of glucose-VGO blends was conducted based on modified random pore model using TGA experimental data and implemented in MATLAB. The estimated activation energy and rate constants were found to be consistent to the observed co-gasification rates. The apparent activation energies of co-gasification of VGO/biomass blends with different weight percentages shows values ranging 60.56-48.25 kJ/mol. The kinetics analysis suggested that the addition of biomass helped to increase the reaction rate by lowering the activation energy required for accomplishing the reactions compared with petroleum carbonaceous feedstocks. The reaction rate constants isotherms are plotted to show that the k-values are exhibiting similar trends at moderate heating rates between 20 and 60 °C/min. This remark arises due to the nature of the reactions involved which are considered to be inherently similar in this range of heating rate.About 40% of non-small lung cancer (NSCLC) patients have metastatic disease at the time of diagnosis. However, metastatic NSCLC in the biliary duct system is extremely rare. WM-8014 inhibitor A high proportion of patients with acute liver failure due to advanced NSCLC do not receive any treatment due to organ dysfunction or poor performance status. Here, we report a case of successful treatment with chemoimmunotherapy in a young woman with obstructive jaundice and acute hepatic failure due to multiple intrahepatic bile duct metastases. KEY POINTS Significant findings of the study Chemotherapy in NSCLC patients with liver failure is a therapeutic challenge. Acute hepatic failure are often exclusion criteria for therapy of NSCLC. Some reports showed a benefit of ICIs plus chemotherapy for NSCLC with liver metastases. What this study adds Combination of ICIs and chemotherapy is effective and safe in critically ill patients with lung cancer and impaired liver function.

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