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Background: This study aimed to overexpress or silence connexin 43 (Cx43) and A‐kinase anchoring protein 95 (AKAP95) in human A549 cells to explore their effects on cyclins and on G1/S conversion when the interrelationship of Cx43, AKAP95, and cyclin E1/E2 changes. Methods: The study mainly used Western blot analysis and Co‐immuno precipitation to detect the target protein in Cx43/AKAP95 over expressed human A549 cells, and the relationship of proteins Cx43, AKAP95 and Cyclin E during G1‐S phase was explored with qualitative and quantitative analysis. Results: The overexpression of Cx43 inhibited the expression of cyclin D1 and E1 by accelerating their degradation and reduced the Cdk2 activity that blocked the DNA transcription activity. However, the overexpression of AKAP95 increased the expression of cyclin D1 and E1 and inhibited their degradation, and enhanced the Cdk2 activity that promoted the DNA transcription activity. Cx43 and AKAP95 competitively bound to cyclin E1/E2, and the competitive binding affected the Cdk2 activity, Rb phosphorylation, DNA transcription activity, and G1/S conversion. Conclusions: This study showed that the expression of ERK1/2, PKA, and PKB increased when BEAS‐2B cells were treated with PDGF‐BB, suggesting that ERK1/2, PKA, and PKB might be involved in the binding of AKAP95 with cyclin E, or the separation of AKAP95 from Cx43 from cyclin E1/E2. The specific mechanism underlying this process still needs further exploration. [ABSTRACT FROM AUTHOR]

Cigarettes contain various chemicals with the potential to influence metabolic health. Exposure to cigarette smoke causes a dysfunction in pancreatic β‐cells and impairs insulin production. However, the mechanisms for cigarette smoke‐induced reduction of insulin remain largely unclear. Data from 558 patients with diabetes showed that, with smoking pack‐years, homeostatic model assessment (HOMA)‐β (a method for assessing β‐cell function) decreased and that HOMA of insulin resistance increased. For β‐cells (MIN6), cigarette smoke extract (CSE) increased the levels of thioredoxin‐interacting protein (TXNIP) and the long noncoding (lnc)RNA, metastasis‐associated lung adenocarcinoma transcript 1 (MALAT1), and downregulated the levels of the transcription factor, mafA, and microRNA (miR)‐17. MALAT1, one of four lncRNAs predicted to regulate miR‐17, was knocked down by small interfering RNA (siRNA). For these cells, an miR‐17 mimic inhibited TXNIP and enhanced the production of insulin. Knockdown of MALAT1 induced an increase in miR‐17, which suppressed TXNIP and promoted the production of insulin. In the sera of patients with diabetes who smoked, there were higher MALAT1 levels and lower miR‐17 levels than in the sera of nonsmokers. Thus, CSE inhibits insulin production by upregulating TXNIP via MALAT1‐mediated downregulation of miR‐17, which provides an understanding of the processes involved in the reduced β‐cells function caused by cigarette smoke. [ABSTRACT FROM AUTHOR]

Background This study was conducted to investigate the exchange protein directly activated by c AMP ( Epac1), PDE4, and PKC expression in breast cancer tissues, and the correlation between these proteins and AKAP95, Cx43, cyclin D2, and cyclin E1. Methods PV-9000 two-step immunohistochemistry was used to analyze protein expression. Results The positive rate of Epac1 protein expression in breast cancer tissues (58%) was higher than in para-carcinoma tissues (10%) ( P < 0.05). There were no significant differences in the positive rates of PDE4 and PKC expression between breast cancer and para-carcinoma tissues ( P > 0.05). The positive expression rate of PDE4 was higher in the P53 protein positive group compared to the P53 negative group ( P < 0.05). Correlations between Epac1 and cyclin D2, PDE4 and cyclin D2, AKAP95 and PKC, Cx43 and PKC, and cyclin D2 and PKC proteins were observed ( P < 0.05). Conclusion Epac1 expression in breast cancer tissues was increased, suggesting that the protein may be involved in the development of breast cancer. Correlations between Epac1 and cyclin D2, PDE4 and cyclin D2, AKAP95 and PKC, Cx43 and PKC, and cyclin D2 and PKC proteins suggested synergistic effects among these proteins in the development of breast cancer. [ABSTRACT FROM AUTHOR]

Background Peroxisome proliferator-activated receptor gamma ( PPAR γ) signaling has been shown to regulate lipogenesis and lipid accumulation. Previous studies have shown that hepatic PPAR γ is up-regulated in steatotic liver of both animal and human. However, the effects of hepatic PPAR γ signaling on alcoholic liver disease ( ALD) remain elusive. Methods To determine the role of hepatic PPAR γ signaling on ALD, wild-type ( WT) and hepatocyte-specific PPAR γ knockdown ( PPAR γ∆ Hep) mice were fed a modified Lieber- De Carli alcohol or isocaloric maltose dextrin control liquid diet for 8 weeks to induce ALD. Blood parameters, hepatic steatosis, and inflammation were measured after 8-week alcohol feeding. Results Alcohol feeding to WT mice resulted in liver damage (alanine aminotransferase [ ALT], 94.68 ± 17.05 U/L; aspartate aminotransferase [ AST], 55.87 ± 11.29 U/L), which was significantly alleviated by hepatic PPAR γ knockdown ( ALT, 57.36 ± 14.98 U/L; AST, 38.06 ± 3.35 U/L). Alcohol feeding led to marked lipid accumulation and up-regulation of lipogenic genes including fatty acid transport protein 1 ( FATP1), acetyl- Co A carboxylase ( ACC), fatty acid synthase ( FASN), lipin1 (LIPIN1), diacylglycerol acyltransferase 1 ( DGAT1), and diacylglycerol acyltransferase 2 ( DGAT2) in the livers of WT mice. Knockdown of hepatic PPAR γ significantly alleviated alcohol-induced lipid accumulation and abolished the up-regulation of FASN, DGAT1, and DGAT2. Silencing of PPAR γ in FL83 B cells significantly decreased ethanol ( Et OH)-, linoleic acid-, and Et OH plus linoleic acid-induced lipid accumulation. Knockdown of hepatic PPAR γ also significantly reduced alcohol-induced inflammatory chemokine (monocyte chemotactic protein 1 [ MCP1], keratinocyte-derived chemokine [ KC], interferon gamma-induced protein 10 [ IP-10]) and inflammatory infiltration (lymphocyte antigen 6 complex, locus G [ Ly6 G], and F4/80). Conclusions The results suggest that hepatic PPAR γ signaling contributes to alcohol-induced liver injury by promoting hepatic steatosis and inflammation. [ABSTRACT FROM AUTHOR]

Cucumber is a model cucurbitaceous plant with a known genome sequence which is important for studying molecular mechanisms of root development. In this study, RNA sequencing was employed to explore the mechanism of melatonin-induced lateral root formation in cucumber under salt stress. Three groups of seeds were examined, that is, seeds primed without melatonin ( CK), seeds primed in a solution containing 10 or 500 μmol/L melatonin (M10 and M500, respectively). These seeds were then germinated in NaCl solution. The RNA-seq analysis generated 16,866,670 sequence reads aligned with 17,920 genes, which provided abundant data for the analysis of lateral root formation. A total of 17,552, 17,450, and 17,393 genes were identified from roots of the three treatments ( CK, M10 and M500, respectively). The expression of 121 genes was significantly up-regulated, and 196 genes were significantly down-regulated in M500 which showed an obvious increase on the number of lateral roots. These genes were significantly enriched in 57 KEGG pathways and 16 GO terms (M500 versus CK). Based on their expression pattern, peroxidase-related genes were selected as the candidates to be involved in the melatonin response. Several transcription factor families might play important roles in lateral root formation processes. A number of genes related to cell wall formation, carbohydrate metabolic processes, oxidation/reduction processes, and catalytic activity also showed different expression patterns as a result of melatonin treatments. This RNA-sequencing study will enable the scientific community to better define the molecular processes that affect lateral root formation in response to melatonin treatment. [ABSTRACT FROM AUTHOR]

Background This study examined the expression of exchange protein directly activated by c AMP1 ( Epac1), PDE4, and PKC in esophageal cancer tissues, and analyzed the association of each protein with the pathological parameters of the samples. Methods Epac1, PDE4, and PKC protein expression was evaluated by PV-9000 two-step immunohistochemical techniques in 51 esophageal cancer specimens and 10 para-carcinoma tissues. Results The positive expression rates of Epac1 and PKC in esophageal cancer tissues (62.7% and 68.6%, respectively) were higher compared to those in para-carcinoma tissues (20% and 20%, respectively) ( P < 0.05). The positive expression rate of PDE4 in esophageal cancer tissues (54.1%) was higher than in para-carcinoma tissues (30%), ( P > 0.05). Epac1, PDE4, and PKC protein expression levels were not associated with the extent of tumor differentiation and/or lymph node metastasis ( P > 0.05). Epac1 protein expression levels correlated with PDE4, PKC, and AKAP95 protein expression levels. In addition, there was a correlation between PKC and Cx43 protein levels ( P < 0.05). Conclusion The expression rates of Epac1, PDE4, and PKC protein in esophageal cancer tissues were significantly higher compared to the rates in para-carcinoma tissues, suggesting an association between these proteins and the development and progression of esophageal cancer. The correlations between these proteins also revealed that they may exert a synergistic effect during the development of esophageal cancer. [ABSTRACT FROM AUTHOR]