[leukocyte-associated immunoglobulin-like receptor 1 (LAIR-1) inhibits proliferation and promotes apoptosis of human HEL cells with JAK2 V617F mutation by blocking the JAK/STAT and PI3K/AKT signaling pathways].

Objective To investigate the role of human leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) in the regulation of Janus kinase/signal transducers and activators of transcription (JAK/STAT) and phosphatidylinositol 3 kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT /mTOR) signaling pathways in human acute myeloid leukemia HEL cells carrying the JAK2 V617F mutation, along with its effects on cell proliferation and apoptosis. MethodsThe JAK2 V617F mutation was identified using reverse transcription PCR and gene sequencing. The protein phosphatase (PTP) recruited by LAIR-1 was determined through co-immunoprecipitation and Western blot analysis. The proliferation of HEL cells was detected by CCK-8 assay. The apoptosis rate of HEL cells was detected by flow cytometry with annexin V-FITC/PI labeling. Western blot analysis was employed to assess the phosphorylation status of proteins involved in the JAK/STAT and PI3K/AKT/mTOR pathways, as well as the expression levels of cyclinD1, B cell lymphoma 2 (Bcl2), and Bcl2 associated X protein (BAX). Results In HEL cells containing the JAK2 V617F mutation, LAIR-1 was observed to recruit SH2-containing protein tyrosine phosphatase 2 (SHP-2) upon binding with its ligand collagen. Moreover, LAIR-1 downregulated the tyrosine phosphorylation levels of JAK2, STAT1, STAT3, STAT5, AKT and mTOR and significantly reduced the expression of cyclin D1 and Bcl2, while having no effect on the expression of BAX. In addition, LAIR-1 exhibited a significantly inhibitory effect on cell proliferation and promoted apoptosis in HEL cells. Conclusion In HEL cells with JAK2 V617F mutation, LAIR-1 can inhibit the activation of JAK/STAT and PI3K/AKT/mTOR signaling pathways by recruiting SHP-2, thereby inhibiting the proliferation of HEL cells and promoting cell apoptosis.

Phototriggered Self-Catalyzed Three-Component Minisci Reaction: A Route to ß-C(sp3) Heteroarylated Alcohols/Ethers.

Herein, a visible-light-triggered photocatalyst-free radical cascade Minisci reaction of heteroarenes, alkenes, and water/alcohols to obtain diverse ß-C(sp3) heteroarylated alcohols/ethers has been developed. Achieved under mild and simple conditions, this protocol is scalable and features broad substrate scope and functional group tolerance. Mechanistic studies demonstrate that the heteroarene can be served as a photocatalyst to engage single-electron transfer with persulfate.

Electrochemical Oxidative C-H Arylation of Quinoxalin(on)es with Arylhydrazine Hydrochlorides under Mild Conditions.

A practical and scalable protocol for electrochemical arylation of quinoxalin(on)es with arylhydrazine hydrochlorides under mild conditions has been developed. This method exhibits high efficiency, easy scalability, and broad functional group tolerance. Various quinoxalin(on)es and arylhydrazines underwent this transformation smoothly in an undivided cell, providing the corresponding aryl-substituted quinoxalin(on)es in moderate to good yields. A radical mechanism is involved in this arylation reaction.

Electrochemically C-H/S-H Oxidative Cross-Coupling between Quinoxalin-2(1H)-ones and Thiols for the Synthesis of 3-Thioquinoxalinones.

An electrochemical method for the C(sp2)-H thioetherification of quinoxalin-2(1H)-ones with primary, secondary, and tertiary thiols has been reported. Various quinoxalin-2(1H)-ones underwent this thioetherification smoothly under metal- and chemical oxidant-free conditions, affording 3-alkylthiol-substituted quinoxalin-2(1H)-ones in moderate to good yields.

Visible-Light-Induced para-Selective C(sp2)-H Difluoroalkylation of Diverse (Hetero)aromatic Carbonyls.

An efficient visible-light-induced para-selective C(sp2)-H difluoroalkylation of diverse electron-deficient (hetero)aromatic carbonyls (aldehydes and ketones) at ambient temperature has been developed by employing Ir(ppy)3 as the catalyst and 1,10-phenanthroline as the additive. This protocol was highlighted by its wide substrate scope, high regioselectivity, low catalyst usage, and operational simplicity.

Catalyst-free regioselective hydroxyfluorination and aminofluorination of α,ß-unsaturated ketones.

The catalyst-free direct regioselective α-fluoro-ß-hydroxylation and α-fluoro-ß-amidation of α,ß-unsaturated ketones has been developed. Various α,ß-unsaturated ketones react with Selectfluor in water and acetonitrile to give α-fluorohydrins and α-fluoroamides respectively with moderate to good yields. The mechanistic studies revealed the possibility of a radical based pathway.

Clinicopathologic significance of LAIR-1 expression in hepatocellular carcinoma.

AIM: Leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) is an immune inhibitory receptor which is expressed within most types of hematopoietic cells and negatively regulates immune responses. Recently, we found LAIR-1 expression to be present within tumors of nonhematopoietic lineages. However, the roles of LAIR-1 in hepatocellular carcinoma (HCC) have yet to be examined. The purpose of this study was to investigate the expression of LAIR-1 in HCC tissue and assess its clinical significance at this site. MATERIALS AND METHODS: Expression levels of LAIR-1 within HCC samples collected from 90 patients and compared with that of slides of normal liver tissue collected from 9 non-HCC patients were measured by immunohistochemistry using tissue microarrays. A semiquantitative score was assigned, as was based on staining intensity and percent of positive cells and a Spearman Rank correlation test was used to assess any potential significant correlations between LAIR-1 expression and clinicopathological factors. Overall survival analysis was performed using the Kaplan-Meier and Log Rank statistical test. RESULTS: LAIR-1 expression was detected in cancer tissue and adjacent tumor tissue, but not in normal liver tissue. The percent of LAIR-1-positive expression in cancer tissue of HCC samples was 97.78% (88/90) while that in adjacent tumor tissue was 96.67% (87/90). Significantly greater expression levels of LAIR-1 were obtained from cancer tissue (Mean ±â€¯SD = 5.722 ±â€¯2.145) than that in adjacent tumor tissue (4.141 ±â€¯1.486). In addition, LAIR-1 expression was found to be significantly correlated with pathological grade of HCC, T stage, and age. Expression levels of LAIR-1 were related with worse overall survival rates of HCC patients, especially in HCC patients with hepatic cirrhosis. CONCLUSION: Results of this study show that LAIR-1 is expressed in HCC tissues and that high levels of LAIR-1 expression are associated with the poor cancer differentiation. In addition, overexpression of LAIR-1 was significantly associated with worse overall survival in the patients with HCC. These data suggest that LAIR-1 may be an independent predictor for clinical outcomes in patients with HCC.

Leukocyte-associated immunoglobulin-like receptor-1 expressed in epithelial ovarian cancer cells and involved in cell proliferation and invasion.

Previous studies have shown that leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) is expressed on most types of hamatopoietic cells and negatively regulate immune response, but the roles of LAIR-1 in tumor of the non-hematopoietic lineage have not been determined. Despite advances in therapy of epithelial ovarian cancer (EOC), many questions relating to EOC pathogenesis remain unanswered. The aim of this study was to investigate the clinical significance of LAIR-1 expression in EOC and explore the possible association between LAIR-1 and cancer. In this study, a tissue microarray containing 78 ovarian cancer cases was stained following a standard immunohistochemical protocol for LAIR-1 and the correlation of LAIR-1 expression with clinicopathologic features was assessed. LAIR-1 was detected to express in tumor cells of ovarian cancer tissues (73.1%) and EOC cell lines COC1 and HO8910, not in normal ovarian tissues. In addition, LAIR-1 expression correlates significantly with tumor grade (p = 0.004). Furthermore, down-regulation of LAIR-1 in HO8910 cells increased cell proliferation, colony formation and cell invasion. These data suggest that LAIR-1 has a relevant impact on EOC progression and may be helpful for a better understanding of molecular pathogenesis of cancer.