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Lysosomal dysfunction and impaired autophagic flux are involved in the pathogenesis of lipotoxicity in the kidney. Here, we investigated the role of transcription factor EB (TFEB), a master regulator of autophagy-lysosomal pathway, in palmitic acid induced renal tubular epithelial cells injury. We examined lipid accumulation, autophagic flux, expression of Ps211-TFEB, and nuclear translocation of TFEB in HK-2 cells overloaded with palmitic acid (PA). By utilizing immunohistochemistry, we detected TFEB expression in renal biopsy tissues from patients with diabetic nephropathy and normal renal tissue adjacent to surgically removed renal carcinoma (controls), as well as kidney tissues from rat fed with high-fat diet (HFD) and low-fat diet (LFD). We found significant lipid accumulation, increased apoptosis, accompanied with elevated Ps211-TFEB, decreased nuclear TFEB, reduced lysosome biogenesis and insufficient autophagy in HK-2 cells treated with PA. Kidney tissues from patients with diabetic nephropathy had lower nuclear and total levels of TFEB than that in control kidney tissues. Level of renal nuclear TFEB in HFD rats was also lower than that in LFD rats. Exogenous overexpression of TFEB increased the nuclear TFEB level in HK-2 cells treated with PA, promoted lysosomal biogenesis, improved autophagic flux, reduced lipid accumulation and apoptosis. Our results collectively indicate that PA is a strong inducer for TFEB phosphorylation modification at ser211 accompanied with lower nuclear translocation of TFEB. Impairment of TFEB-mediated lysosomal biogenesis and function by palmitic acid may lead to insufficient autophagy and promote HK-2 cells injury. • PA oversupply increased serine phosphorylation of TFEB at ser211 and reduces TFEB nuclear translocation in HK-2 cells. • Decreased nuclear distribution of TFEB ensuing impaired lysosomal biogenesis and insufficient autophagy. • The content of TFEB in renal tissue of diabetic nephropathy patients and HFD rats was lower than that of control group. • Overexpression of TFEB counteracts the impaired lysosome biogenisis and insufficient autophagy caused by PA intervention. [ABSTRACT FROM AUTHOR]

Graphical abstract The LDHs were delaminated to test their catalytic performance of syngas in the aqueous phase in a batch stirred reactor. The catalytic activity of 0.055–0.675 mol CO · mol Co - 1 · h - 1 and selectivity (S Oxy = 75–88%) to oxygenates (C 2) were observed. Abstract Layered double hydroxides (LDHs) were innovatively employed in this study as catalyst for synthesis gas conversion to chemicals, such as oxygenates. Cobalt-aluminium layered double hydroxides (Co-Al LDHs) was prepared at different temperatures. and lactate was successfully intercalated into the LDHs by ion-exchange method and then the material was further delaminated in water at ambient temperature. The samples were characterized by SEM, TEM and AFM, and separately dispersed nanosheets can be clearly observed. The prepared lamellas were applied in aqueous-phase synthesis gas conversion reaction. The catalysts generated a superior activity of 0.055–0.675 mol CO · mol Co - 1 · h - 1 and greater oxygenated product (acetaldehyde) selectivity (S Oxy = 75–88%) than conventional cobalt Fisher-Tropsch (FT) synthesis catalysts. Ammonium ion showed some effect of the selectivity of the acetaldehyde. The original research results suggested a promising application of the mono-dispersed ultrathin cobalt-bearing LDHs nanosheets in the aqueous phase syngas conversion to valuable oxygenate products. [ABSTRACT FROM AUTHOR]

Abstract CircRNAs are reported to be implicated in the development of lung cancer. This study focused on assessing the expression, functions and molecular mechanism of circPUM1 in lung adenocarcinoma. Here, it showed that circPUM1 is significantly upregulated in both lung adenocarcinoma cell lines and tissues. Furthermore, silencing of circPUM1 impaired the proliferation, migration and invasion ability, and increased apoptosis in A549 cells. Nevertheless, overexpression of circPUM1 in SPC-A1 cells has the opposite effect. Silencing of circPUM1 inhibits the tumorigenesis in nude mice. Mechanistically, circPUM1 could sponge miR-326 and promote the expression of its downstream proteins Cyclin D1 and Bcl-2. In summary, this present study revealed that circPUM1 functions as an oncogene to promote the tumorigenesis of lung adenocarcinoma through circPUM1/miR-326/Cyclin D1 and Bcl-2 axis. This indicates that circPUM1 may act as a potential therapeutic target for lung adenocarcinoma. Highlights • Upregulation of circPUM1 in lung adenocarcinoma cell lines and tissues. • Silencing of circPUM1 inhibits the proliferation, migration, invasion and inhibited apoptosis in vitro, and vice versa. • CircPUM1 sponges miR-326 to upregulate Cyclin D1 and Bcl-2 expression to promote tumorigenesis. [ABSTRACT FROM AUTHOR]

MicroRNAs are a large class of tiny noncoding RNAs, which have emerged as critical regulators of gene expression, and thus are involved in multiple cellular processes, including cellular senescence. MicroRNA-33 has previously been established to exert crucial effect on cell proliferation, lipid metabolism and cholesterol metabolism. Nonetheless, the association between microRNA-33 and cellular senescence and its underlying molecular mechanism are far to be elucidated. The present study has attempted to probe into the effect of microRNA-33 on MEFs senescence. Our data unveiled that microRNA-33 was dramatically down-regulated in senescent MEFs compared to the young MEFs, and ectopic expression of microRNA-33 promoted MEFs senescence, while knock-down of microRNA-33 exhibited a protective effect against senescence phenotype. Moreover, we verified CDK6 as a direct target of microRNA-33 in mouse. Silencing of CDK6 induced the premature senescence phenotype of MEFs similarly as microRNA-33, while enforced expression of CDK6 significantly reverse the senescence-induction effect of microRNA-33. Taken together, our results suggested that microRNA-33 enhanced the replicative senescence of MEFs potentially by suppressing CDK6 expression. [ABSTRACT FROM AUTHOR]

T cell activation is a complicated process accompanying with the activation of T cell receptor (TCR) signaling pathway, which is not well described in teleost fish. The initiation of this pathway depends on the interaction of membrane TCR co-receptors (e.g. CD4/8, CD3 and CD45) and a series of cytoplasmic protein tyrosine kinases (e.g. Lck, Fyn and ZAP70). Cyptocaryon irritans is a ciliate pathogen of marine fish white spot disease causing huge economic lost in marine aquaculture. This parasite can infect fish gill and skin and is considered to be a good pathogen model for fish gill and skin mucosal immunity. Our previous studies showed the locally mucosal antibody response was important for fish defense against this parasite. While how TCR signaling pathway involved in T cell activation to help B cell activation in C. irritans infected fish is still not known. In the present study, we cloned a grouper TCR co-receptor gene EcCD3ε (537 bp) and its three kinase genes, including EcLck (1512 bp), EcFyn (1605 bp) and EcZAP70 (1893 bp). Homology analysis showed that they all shared the highest identity with corresponding genes from Takifugu rubripes (EcCD3ε 41%, EcLck 88%, EcFyn 98% and EcZAP70 93%), and their conserved motifs involved in the signaling transduction were analyzed. The tissue distribution analysis showed these four genes were high expressed in thymus, and it is interesting to find their comparative high expression in skin, gill and midgut mucosal immune tissues. In C. irritans infected grouper, the expression of three TCR co-receptors (EcCD4-1, EcCD3ε and EcCD45) and three kinases (EcLck, EcFyn and EcZAP70) was tested in skin, gill, head kidney and spleen at 0, 12 h, 24 h, 2 d, 3 d, 5 d and 7 d. All six genes were significantly up-regulated in skin at most tested time points, which indicate the possibility of skin local T cell activation to support the local antibody response. Compared to three TCR co-receptors, significantly up-regulation of three kinases were seen in the spleen, and the spleen fold changes of these three kinases were much higher than head kidney, which indicates spleen maybe the major systematic immune organs for T cell activation in C. irritans infected fish. [ABSTRACT FROM AUTHOR]

Circular RNAs (circRNAs), characterized as single-stranded closed circular RNA molecules, have been established to exert pivotal functions in various biological or pathological processes. Nonetheless, the effects and underlying mechanisms concerning circRNAs on the aging and aging-related diseases remain elusive. We herein compared the expression patterns of circRNAs in young and senescent mouse embryonic fibroblasts (MEFs), and uncovered that circRNF169 was dramatically up-regulated in senescent MEFs compared with that in young MEFs. Therefore, we further digged into the role and potential mechanisms of circRNF169 in the senescence of MEFs. The results of senescence-associate-β-galactosidase staining and BrdU incorporation assay showed that silencing of circRNF169 significantly delayed MEFs senescence and promoted cell proliferation, while ectopic expression of circRNF169 exhibited the opposite effects. Moreover, the dual-luciferase reporter assay confirmed that circRNF169 acted as an endogenous miR-30c-5p sponge, which accelerated cellular senescence by sequestering and inhibiting miR-30c-5p activity. Taken together, our results suggested that circRNF169 exerted a crucial role in cellular senescence through sponging miR-30c-5p and represented a promising target for aging intervention. • CircRNF169 was dramatically up-regulated in senescent MEFs. • CircRNF169 significantly promoted the replicative senescence of MEFs. • CircRNF169 promoted the replicative senescence of MEFs through acting as a miR-30c-5p sponge. [ABSTRACT FROM AUTHOR]

Abstract: Vascular endothelial growth factor (VEGF) was investigated in the present study to see whether it could provide a therapeutic opportunity for the treatment of Alzheimer’s disease (AD). PDGF-hAPPV717I transgenic mice were treated with VEGF or PBS by intraperitoneal injection for three consecutive days. The results showed that VEGF ameliorated the memory impairment of mice, accompanied by CD34+ cells increasing in peripheral blood, vWF+ vessels increasing in hippocampus, and CD34+/VEGFR2+, vWF+/VEGFR2+ and BrdU+/vWF+ cells expressing in hippocampus. Furthermore, the level of choline acetyltransferase (ChAT) was considerably enhanced and Aβ deposition was decreased in the brains of mice upon VEGF treatment. These observations suggest that VEGF should be pursued as a novel therapeutic agent for treatment of AD. [Copyright &y& Elsevier]

Abstract: MicroRNAs are important posttranscriptional regulators of gene expression in animals and plants. A sensitive and specific detection method is urgently needed for intensive studies on differential expression and regulatory roles of microRNA. Here we present a simple and reliable method for the quantification of microRNA. The hybridization products of target microRNA with capture probe and gold nanoparticle probe are immobilized onto the surface of a streptavidin-coated microplate, and the signal is amplified by silver enhancement. Distribution of miR-122a/miR-128 in mouse brain and liver tissue was detected by this method, and synthetic miRNA122a was quantified. This method allowed a lower detect limit of 10fM with a linear dynamic range from 10pM to 10fM and a high specificity to discriminate one single oligonucleotide mismatch of the target microRNA. [Copyright &y& Elsevier]