Effect of sarcopenia on survival of patients with cirrhosis: A meta-analysis

The association between sarcopenia and prognosis in patients with cirrhosis remains to be determined. In this study, we aimed to quantify the association between sarcopenia and the risk of mortality in patients with cirrhosis, by sex, underlying liver disease etiology, and severity of hepatic dysfunction.PubMed, Web of Science, EMBASE, and major scientific conference sessions were searched without language restriction through 13 January 2021 with additional manual search of bibliographies of relevant articles. Cohort studies of ?100 patients with cirrhosis and ?12 months of follow-up that evaluated the association between sarcopenia, muscle mass and the risk of mortality were included.22 studies with 6965 patients with cirrhosis were included. The pooled prevalence of sarcopenia in patients with cirrhosis was 37.5% overall (95% CI 32.4%-42.8%), higher in male patients, patients with alcohol associated liver disease (ALD), patients with CTP grade C, and when sarcopenia was defined in patients by lumbar 3- skeletal muscle index (L3-SMI). Sarcopenia was associated with the increased risk of mortality in patients with cirrhosis (adjusted-hazard ratio [aHR] 2.30, 95% CI 2.01-2.63), with similar findings in sensitivity analysis of cirrhosis patients without HCC (aHR 2.35, 95% CI 1.95-2.83) and in subgroup analysis by sex, liver disease etiology, and severity of hepatic dysfunction. The association between quantitative muscle mass index and mortality further supports the poor prognosis for patients with sarcopenia (aHR 0.95, 95% CI 0.93-0.98). There was no significant heterogeneity in all analyses.Sarcopenia was highly and independently associated with higher risk of mortality in patients with cirrhosis.The prevalence of sarcopenia and its association with death in patients with cirrhosis remain unclear. This meta-analysis indicated that sarcopenia affected about one-third of patients with cirrhosis and up to 50% in patients with ALD or Child's class C cirrhosis. Sarcopenia was independently associated with about 2-fold higher risk of mortality in patients with cirrhosis. The mortality rate increased with greater severity or longer period of having sarcopenia. Increasing awareness about the importance of sarcopenia in patients with cirrhosis among stakeholders must be prioritized

Arabidopsis CPR5 Independently Regulates Seed Germination and Postgermination Arrest of Development through LOX Pathway and ABA Signaling

The phytohormone abscisic acid (ABA) and the lipoxygenases (LOXs) pathway play important roles in seed germination and seedling growth and development. Here, we reported on the functional characterization of Arabidopsis CPR5 in the ABA signaling and LOX pathways. The cpr5 mutant was hypersensitive to ABA in the seed germination, cotyledon greening and root growth, whereas transgenic plants overexpressing CPR5 were insensitive. Genetic analysis demonstrated that CPR5 gene may be located downstream of the ABI1 in the ABA signaling pathway. However, the cpr5 mutant showed an ABA independent drought-resistant phenotype. It was also found that the cpr5 mutant was hypersensitive to NDGA and NDGA treatment aggravated the ABA-induced delay in the seed germination and cotyledon greening. Taken together, these results suggest that the CPR5 plays a regulatory role in the regulation of seed germination and early seedling growth through ABA and LOX pathways independently

Evaluation of metals that are potentially toxic to agricultural surface soils, using statistical analysis, in northwestern Saudi Arabia

© 2015, Springer-Verlag Berlin Heidelberg. Heavy metals in agricultural soils enter the food chain when taken up by plants. The main purpose of this work is to determine metal contamination in agricultural farms in northwestern Saudi Arabia. Fifty surface soil samples were collected from agricultural areas. The study focuses on the geochemical behavior of As, Cd, Co, Cr, Cu, Hg, Pb and Zn, and determines the enrichment factor and geoaccumulation index. Multivariate statistical analysis, including principle component analysis and cluster analysis, is also applied to the acquired data. The study shows considerable variation in the concentrations of the analyzed metals in the studied soil samples. This variation in concentration is attributed to the intensity of agricultural activities and, possibly, to nearby fossil fuel combustion activities, as well as to traffic flows from highways and local roads. Multivariate analysis suggests that As, Cd, Hg and Pb are associated with anthropogenic activities, whereas Co, Cr, Cu and Zn are mainly controlled by geogenic activities. Hg and Pb show the maximum concentration in the analyzed samples as compared to the background concentration

Therapeutic landscape in mutational triple negative breast cancer

Abstract Triple negative breast cancer (TNBC) is a heterogeneous disease with aggressive behavior and poor prognosis. Genomic sequencing has detected a distinctive mutational portrait of both the germline and somatic alterations in TNBC, which is staggeringly different from other breast cancer subtypes. The clinical utility of sequencing germline BRCA1/2 genes has been well established in TNBC. However, for other predisposition genes, studies concerning the risk and penetrance to TNBC are relatively scarce. Very few recurrent mutations, including TP53 and PI3KCA mutations, together with a long tail of individually rare mutations occur in TNBC. These combined effects of genomic alterations drive TNBC progression. Given the complexity and heterogeneity of TNBC, clinical interpretation of the genomic alterations in TNBC may pave a new way for the treatment of TNBC. In this review, we summarized the germline and somatic mutation profiles of TNBC and discussed the current and upcoming therapeutic strategies targeting the mutant proteins or pathways to enable tailored-therapeutics

DAXX, as a Tumor Suppressor, Impacts DNA Damage Repair and Sensitizes BRCA-Proficient TNBC Cells to PARP Inhibitors

Treatment options are limited for patients with triple negative breast cancer (TNBC). Understanding genes that participate in cancer progression and DNA damage response (DDR) may improve therapeutic strategies for TNBC. DAXX, a death domain-associated protein, has been reported to be critically involved in cancer progression and drug sensitivity in multiple cancer types. However, its role in breast cancer, especially for TNBC, remains unclear. Here, we demonstrated a tumor suppressor function of DAXX in TNBC proliferation, colony formation, and migration. In Mouse Xenograft Models, DAXX remarkably inhibited tumorigenicity of TNBC cells. Mechanistically, DAXX could directly bind to the promoter region of RAD51 and impede DNA damage repair, which impacted the protection mechanism of tumor cells that much depended on remaining DDR pathways for cell growth. Furthermore, DAXX-mediated inefficient DNA damage repair could sensitize BRCA-proficient TNBC cells to PARP inhibitors. Additionally, we identified that dual RAD51 and PARP inhibition with RI-1 and ABT888 significantly reduced TNBC growth both in vitro and in vivo, which provided the first evidence of combining RAD51 and PARP inhibition in BRCA-proficient TNBC. In conclusion, our data support DAXX as a modulator of DNA damage repair and suppressor of TNBC progression to sensitize tumors to the PARP inhibitor by repressing RAD51 functions. These provide an effective strategy for a better application of PARP inhibition in the treatment of TNBC

Preparation and Characterization of Nanoporous Activated Carbon Derived from Prawn Shell and Its Application for Removal of Heavy Metal Ions

The aim of this study was to optimize the adsorption performance of activated carbon (AC), derived from the shell of Penaeus vannamei prawns, on heavy metal ions. Inexpensive, non-toxic, and renewable prawn shells were subjected to carbonization and, subsequently, KOH-activation to produce nanoporous K-Ac. Carbonized prawn shells (CPS) and nanoporous KOH-activated carbon (K-Ac) from prawn shells were prepared and characterized by FTIR, XRD, BET, SEM, and TEM. The results showed that as-produced K-Ac samples were a porous material with microporous and mesoporous structures and had a high specific surface area of 3160 m2/g, average pore size of about 10 nm, and large pore volume of 2.38 m3/g. Furthermore, batches of K-Ac samples were employed for testing the adsorption behavior of Cd2+ in solution. The effects of pH value, initial concentration, and adsorption time on Cd2+ were systematically investigated. Kinetics and isotherm model analysis of the adsorption of Cd2+ on K-Ac showed that experimental data were not only consistent with the Langmuir adsorption isotherm, but also well-described by the quasi-first-order model. Finally, the adsorption behaviors of as-prepared K-Ac were also tested in a ternary mixture of heavy metal ions Cu2+, Cr6+, and Cd2+, and the total adsorption amount of 560 mg/g was obtained