Modulation of Autophagy by Free Fatty Acids

Fatty acids are important molecules with multiple biological properties. Emerging evidence suggests that fatty acids can modulate autophagy. Saturated fatty acids contribute to pancreatic β-cell dysfunction in type 2 diabetes. Palmitic acid, one of the long-chain saturated fatty acids (LCFA), induces autophagy of β-cells which protects them from dysfunctions and apoptotic cell death. Short-chain fatty acids (SCFA) possess antitumor activity in colon cancer cells by promoting autophagy. SCFAs can induce autophagy by suppressing the activity of mTOR signaling. As the most common monosaturated fatty acid (MUFA) in daily nutrition, oleic acid could induce autophagy, which is responsible for the regulation of lipids metabolism in hepatocytes. The ω-3 and ω-6 polyunsaturated fatty acids (PUFA) are essential in normal physiology and metabolism and play a contributory role in the incidence and progress of a series of disease including cancer. Autophagy triggered by ω-3 PUFAs contributes to the cytotoxicity in cancer cells by enhancing apoptosis, while autophagy mediated by ω-6 PUFAs led to the increase in Caenorhabditis elegans lifespan. The recent findings illustrate the potential involvement of autophagy regulation by fatty acids in a number of biological and pathological processes

Coagulation Behavior of Aluminum Salts in Eutrophic Water: Significance of Al13Species and pH Control

The coagulation behavior of aluminum salts in a eutrophic source water was investigated from the viewpoint of Al(III) hydrolysis species transformation. Particular emphasis was paid to the coagulation effect of Al-13 species on removing particles and organic matter. The coagulation behavior of Al coagulants with different basicities was examined through jar tests and hydrolyzed Al(III) speciation distribution characterization in the coagulation process. The results showed that the coagulation efficiency of Al coagulants positively correlated with the content of Al-13 in the coagulation process rather than in the initial coagulants. Aluminum chloride (AlCl3) was more effective than polyaluminum chloride (PACT) in removing turbidity and dissolved organic matter in eutrophic water because AlCl3 could not only generate Al-13 species but also function as a pH control agent in the coagulation process. The solid-state Al-27 NMR spectra revealed that the precipitates formed from AlCl3 and PACT were significantly different and proved that the preformed Al-13 polymer was more stable than the in situ formed one during the coagulation process. Through regulating Al speciation, pH control could improve the coagulation process especially in DOC removal, and AlCl3 benefited most from pH control

Tocilizumab (monoclonal anti-IL-6R antibody) reverses anlotinib resistance in osteosarcoma

PurposeAnlotinib, a tyrosine kinase inhibitor (TKI) has been in clinical application to inhibit malignant cell growth and lung metastasis in osteosarcoma (OS). However, a variety of drug resistance phenomena have been observed in the treatment. We aim to explore the new target to reverse anlotinib resistance in OS.Materials and MethodsIn this study, we established four OS anlotinib-resistant cell lines, and RNA-sequence was performed to evaluate differentially expressed genes. We verified the results of RNA-sequence by PCR, western blot and ELISA assay. We further explored the effects of tocilizumab (anti- IL-6 receptor), either alone or in combined with anlotinib, on the inhibition of anlotinib-resistant OS cells malignant viability by CCK8, EDU, colony formation, apoptosis, transwell, wound healing, Cytoskeletal stain assays, and xenograft nude mouse model. The expression of IL-6 in 104 osteosarcoma samples was tested by IHC.ResultsWe found IL-6 and its downstream pathway STAT3 were activated in anlotinib-resistant osteosarcoma. Tocilizumab impaired the tumor progression of anlotinib-resistant OS cells, and combined treatment with anlotinib augmented these effects by inhibiting STAT3 expressions. IL-6 was highly expressed in patients with OS and correlated with poor prognosis.ConclusionTocilizumab could reverse anlotinib resistance in OS by IL-6/STAT3 pathway and the combination treatment with anlotinib rationalized further studies and clinical treatment of OS

Fungal Community as a Bioindicator to Reflect Anthropogenic Activities in a River Ecosystem

The fungal community interacts with the ambient environment and can be used as a bioindicator to reflect anthropogenic activities in aquatic ecosystems. Several studies have investigated the impact of anthropogenic activities on the fungal community and found that community diversity and composition are influenced by such activities. Here we combined chemical analysis of water properties and sequencing of fungal internal transcribed spacer regions to explore the relationship between water quality indices and fungal community diversity and composition in three river ecosystem areas along a gradient of anthropogenic disturbance (i.e., less-disturbed mountainous area, wastewater-discharge urban area, and pesticide and fertilizer used agricultural area). Results revealed that the level of anthropogenic activity was strongly correlated to water quality and mycoplankton community. The increase in organic carbon and nitrogen concentrations in water improved the relative abundance of Schizosaccharomyces, which could be used as a potential biomarker to reflect pollutant and nutrient discharge. We further applied a biofilm reactor using water from the three areas as influent to investigate the differences in fungal communities in the formed biofilms. Different community compositions were observed among the three areas, with the dominant fungal phyla in the biofilms found to be more sensitive to seasonal effects than those found in water. Finally, we determined whether the fungal community could recover following water quality restoration. Our biofilm reactor assay revealed that the recovery of fungal community would occur but need a long period of time. Thus, this study highlights the importance of preserving the original natural aquatic ecosystem

k-Value-based ferron assay and its application

Al(13) is notable for its promising application in many fields. It has been believed that Al(13) could be assayed in term of Al(b) derived from traditional ferron assay. But the inherent relation between Al(13) and Al(b) is not clear. Here, the new k-value-based ferron assay using nonlinear least squares analysis is suggested to resolve the ambiguity. The experimental results reveal that the moderate kinetics (k value) around 0.001 s(-1) can be ascribed to Al(13). In the short-term aging of freshly neutralized aluminum solutions with OH/Al molar ratio of 2.2, the rapid progress of Al(13)-like transformation into Al(13) can be traced by this method, whereas it may be masked by traditional ferron assay because the metastable intermediates also contribute absorbance to Al(b) fraction. Al(b) can only be regarded as Al(13) when Al(13) forms completely and becomes the stable specie in the matured solution. (C) 2009 Elsevier Inc. All rights reserved

TMEM97/Sigma 2 Receptor Increases Estrogen Receptor α Activity in Promoting Breast Cancer Cell Growth

Aberrant estrogen receptor (ER) signaling is a major driver of breast tumor growth and progression. Sigma 2 receptor has long been implicated in breast carcinogenesis based on pharmacological studies, but its molecular identity had been elusive until TMEM97 was identified as the receptor. Herein, we report that the TMEM97/sigma 2 receptor is highly expressed in ER-positive breast tumors and its expression is strongly correlated with ERs and progesterone receptors (PRs) but not with HER2 status. High expression levels of TMEM97 are associated with reduced overall survival of patients. Breast cancer cells with increased expression of TMEM97 had a growth advantage over the control cells under both nutrition-limiting and sufficient conditions, while the knockdown of TMEM97 expression reduced tumor cell proliferations. When compared to their vector control cells, MCF7 and T47D cells with increased TMEM97 expression presented increased resistance to tamoxifen treatment and also grew better under estrogen-depleted conditions. The TMEM97/sigma 2 receptor enhanced the ERα transcriptional activities and increased the expression of genes responsive to estrogen treatment. Increased TMEM97 also stimulated the mTOR/S6K1 signaling pathways in the MCF7 and T47D cells. The increased level of active, phosphorylated ERα, and the enhanced resistance to tamoxifen treatment with increased TMEM97, could be blocked by an mTOR inhibitor. The knockdown of TMEM97 expression reduced the ERα and mTOR/S6K1 signaling activities, rendering the cells with an increased sensitivity to tamoxifen. The observations suggest that the TMEM97/sigma 2 receptor is a novel regulator of ERα activities in breast tumor cell growth