Galectin-1-Induced Autophagy Facilitates Cisplatin Resistance of Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is one of the most common cancers in Taiwan. Although chemotherapy is the primary treatment for HCC patients, drug resistance often leads to clinical failure. Galectin-1 is a beta-galactoside binding lectin which is up-regulated in HCC patients and promotes tumor growth by mediating cancer cell adhesion, migration and proliferation, but its role in chemoresistance of HCC is poorly understood. In this study we found that galectin-1 is able to lead to chemoresistance against cisplatin treatment, and subsequent inhibition has reversed the effect of cell death in HCC cells. Moreover, galectin-1 was found to induce autophagic flux in HCC cells. Inhibition of autophagy by inhibitors or knockdown of Atg5 cancels galectin-1-induced cisplatin resistance in HCC cells. Increase of mitophagy triggered by galectin-1 was found to reduce the mitochondrial potential loss and apoptosis induced by cisplatin treatment. Finally, using an in situ hepatoma mouse model, we clearly demonstrated that inhibition of galectin-1 by thiodigalactoside could significantly augment the anti-HCC effect of cisplatin. Taken together, our findings offer a new insight into the chemoresistance galectin-1 causes against cisplatin treatment, and points to a potential approach to improve the efficacy of cisplatin in the treatment of HCC patients.     

HUWE1 interacts with BRCA1 and promotes its degradation in the ubiquitin–proteasome pathway

The cellular BRCA1 protein level is essential for its tumor suppression activity and is tightly regulated through multiple mechanisms including ubiquitn–proteasome system. E3 ligases are involved to promote BRCA1 for ubiquitination and degradation. Here, we identified HUWE1/Mule/ARF-BP1 as a novel BRCA1-interacting protein involved in the control of BRCA1 protein level. HUWE1binds BRCA1 through its N-terminus degron domain. Depletion of HUWE1 by siRNA-mediated interference significantly increases BRCA1 protein levels and prolongs the half-life of BRCA1. Moreover, exogenous expression of HUWE1 promotes BRCA1 degradation through the ubiquitin–proteasome pathway, which could explain an inverse correlation between HUWE1 and BRCA1 levels in MCF10F, MCF7 and MDA-MB-231 breast cancer cells. Consistent with a functional role for HUWE1 in regulating BRCA1-mediated cellular response to DNA damage, depletion of HUWE1 by siRNA confers increased resistance to ionizing radiation and mitomycin. These data indicate that HUWE1 is a critical negative regulator of BRCA1 and suggest a new molecular mechanism for breast cancer pathogenesis.     

Exogenous EDDS modifies copper-induced various toxic responses in rice

Copper is a micronutrient required for living organisms, but is potentially toxic in excess. EDDS enhances the phytoextraction of many metals, but the underlying mechanism is fully unclear. Exposure of 200 μM Cu²⁺ for 3 days resulted in rice seedling growth inhibition, accompanied by a decrease in plasma membrane H⁺-ATPase activity, and an increase in relative electrolyte leakage ratios, indicating that maintaining of membrane structure integrity is crucial in acclimation of plants to heavy metal stress. In addition, the chlorophyll and carotenoid content was markedly decreased and the level of the mRNA of Cytochrome P450 gene, OsHMA9, the sulfate transporter gene, and the metallothionein-like protein gene was observed to increase in response to Cu stress. Cu treatment also induced a global epigenetic response which is associated with cell nucleus condensation. These physiological, genetic, and epigenetic responses of rice seedlings to excess copper were modified by the addition of EDDS, suggesting that the supply of EDDS in medium containing a high concentration of Cu ions could enhance plant tolerance potential to excess Cu toxicity through alleviating Cu-induced poisonous effects at various levels.     

Quantitative Detection of 15 Serum Bile Acid Metabolic Products by LC/MS/MS in the Diagnosis of Primary Biliary Cholangitis

To determine 15 bile acid metabolic products in human serum by liquid chromatography-tandem mass spectrometry (LC/MS/MS) and value their diagnostic outcome in primary biliary cholangitis (PBC). Serum from 20 healthy controls and 26 patients with PBC were collected and went LC/MS/MS analysis of 15 bile acid metabolic products. The test results were analyzed by bile acid metabolomics, and the potential biomarkers were screened and their diagnostic performance was judged by statistical methods such as principal component and partial least squares discriminant analysis and area under curve (AUC). 8 differential metabolites can be screened out: Deoxycholic acid (DCA), Glycine deoxycholic acid (GDCA), Lithocholic acid (LCA), Glycine ursodeoxycholic acid (GUDCA), Taurolithocholic acid (TLCA), Tauroursodeoxycholic acid (TUDCA), Taurodeoxycholic acid (TDCA), Glycine chenodeoxycholic acid (GCDCA). The performance of the biomarkers was evaluated by the AUC, specificity and sensitivity. In conclusion, DCA, GDCA, LCA, GUDCA, TLCA, TUDCA, TDCA and GCDCA were identified as eight potential biomarkers to distinguish between healthy people and PBC patients by multivariate statistical analysis, which provided reliable experimental basis for clinical practice.     

Four New C19-Diterpenoid Alkaloids from Aconitum nagarum Stapf

Four new aconitine-type C₁₉-diterpenoid alkaloids, were isolated from the roots of Aconitum nagarum Stapf which were named as nagarutines A–D ( 1–4 ), together with eleven known compounds ( 5–15 ). The structures of the compounds were identified by IR, HR-ESI-MS, 1D and 2D NMR spectra. All compounds were tested for the inhibitory effect on LPS induced NO production in RAW 264.7 macrophages, compound 7 showed moderate anti-inflammatory activity effect and Inhibition rate is about 44.50%.     

Highly Conductive,Light Weight,Robust, Corrosion‐Resistant,Scalable, All‐Fiber Based Current Collectors for Aqueous Acidic Batteries

Lithium‐ion batteries (LIBs) are integral parts of modern technology, but can raise safety concerns because of their flammable organic electrolytes with low flash points. Aqueous electrolytes can be used in LIBs to overcome the safety issues that come with organic electrolytes while avoiding poor kinetics associated with solid state electrolytes. Despite advances in aqueous electrolytes, current collectors for aqueous battery systems have been neglected. Current collectors used in today's aqueous battery systems are usually metal‐based materials, which are heavy, expensive, bulky, and prone to corrosion after prolonged use. Here, a carbon nanotube (CNT)–cellulose nanofiber (CNF) all‐fiber composite is developed that takes advantage of the high conductivity of CNT while achieving high mechanical strength through the interaction between CNT and CNF. By optimizing the CNT/CNF weight ratio, this all‐fiber current collector can be made very thin while maintaining high conductivity (≈700 S cm^?1) and strength (>60 MPa), making it an ideal replacement for heavy metal current collectors in aqueous battery systems.     

Cell type-specific proteomics uncovers a RAF15-SnRK2.6/OST1 kinase cascade in guard cells

Multicellular organisms such as plants contain various cell types with specialized functions. Analyzing the characteristics of each cell type reveals specific cell functions and enhances our understanding of organization and function at the organismal level. Guard cells (GCs) are specialized epidermal cells that regulate the movement of the stomata and gaseous exchange, and provide a model genetic system for analyzing cell fate, signaling, and function. Several proteomics analyses of GC are available, but these are limited in depth. Here we used enzymatic isolation and flow cytometry to enrich GC and mesophyll cell protoplasts and perform in-depth proteomics in these two major cell types in Arabidopsis leaves. We identified approximately 3,000 proteins not previously found in the GC proteome and more than 600 proteins that may be specific to GC. The depth of our proteomics enabled us to uncover a guard cell-specific kinase cascade whereby Raf15 and Snf1-related kinase2.6 (SnRK2.6)/OST1(open stomata 1) mediate abscisic acid (ABA)-induced stomatal closure. RAF15 directly phosphorylated SnRK2.6/OST1 at the conserved Ser175 residue in its activation loop and was sufficient to reactivate the inactive form of SnRK2.6/OST1. ABA-triggered SnRK2.6/OST1 activation and stomatal closure was impaired in raf15 mutants. We also showed enrichment of enzymes and flavone metabolism in GC, and consistent, dramatic accumulation of flavone metabolites. Our study answers the long-standing question of how ABA activates SnRK2.6/OST1 in GCs and represents a resource potentially providing further insights into the molecular basis of GC and mesophyll cell development, metabolism, structure, and function.