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The multilineage differentiation potential of human mesenchymal stem cells (hMSCs) underpins their clinical utility for tissue regeneration. Control of such cell-fate decisions is tightly regulated by different growth factors/cytokines and their cognate receptors. Fibroblast growth factors (FGFs) are among such factors critical for osteogenesis. However, how FGF receptors (FGFRs) help to orchestrate osteogenic progression remains to be fully elucidated. Here, we studied the protein levels of FGFRs during osteogenesis in human adult bone marrow-derived MSCs and discovered a positive correlation between FGFR2 expression and alkaline phosphatase (ALP) activity, an early marker of osteogenesis. Through RNA interference studies, we confirmed the role of FGFR2 in promoting the osteogenic differentiation of hMSCs. Knockdown of FGFR2 resulted in downregulation of pro-osteogenic genes and upregulation of pro-adipogenic genes and adipogenic commitment. Moreover, under osteogenic induction, FGFR2 knockdown resulted in upregulation of Enhancer of Zeste Homolog 2 (EZH2), an epigenetic enzyme that regulates MSC lineage commitment and suppresses osteogenesis. Lastly, we show that serial-passaged hMSCs have reduced FGFR2 expression and impaired osteogenic potential. Our study suggests that FGFR2 is critical for mediating osteogenic fate by regulating the balance of osteo-adipogenic lineage commitment. Therefore, examining FGFR2 levels during serial-passaging of hMSCs may prove useful for monitoring their multipotency.

High Speed train (HST) communication with its analysis of Directivity Beam-width trade off and the hand over scheme is explained in this paper. The analysis does not include channel covariance matrix(CCM) and hence the computation is less complex. The hand off analysis ultimately gives the maximum possible distance between two base stations so as to ensure uninterrupted communication in HST.

Autophagy is considered as an important cell death mechanism that closely interacts with other common cell death programs like apoptosis. Critical role of autophagy in cell death makes it a promising, yet challenging therapeutic target for cancer. We identified a series of 1,2,3-triazole analogs having significant breast cancer inhibition property. Therefore, we attempted to study whether autophagy and apoptosis were involved in the process of cancer cell inhibition. The lead molecule, 1-(1-benzyl-5-(4-chlorophenyl)-1H-1,2,3-triazol-4-yl)-2-(4-bromophenylamino)-1-(4-chlorophenyl)ethanol (T-12) induced significant cell cycle arrest, mitochondrial membrane depolarization, apoptosis and autophagy in MCF-7 and MDA-MB-231 cells. T-12 increased reactive oxygen species and its inhibition by N-acetyl- l -cysteine protected breast cancer cells from autophagy and apoptosis. Autophagy inhibitor, 3-methyladenine abolished T-12 induced apoptosis, mitochondrial membrane depolarization and reactive oxygen species generation. This suggested that T-12 induced autophagy facilitated cell death rather than cell survival. Pan-caspase inhibition did not abrogate T-12 induced autophagy, suggesting that autophagy precedes apoptosis. In addition, T-12 inhibited cell survival pathway signaling proteins, Akt, mTOR and Erk1/2. T-12 also induced significant regression of tumor with oral dose of as low as 10 mg/kg bodyweight in rat mammary tumor model without any apparent toxicity. In presence of reactive oxygen species inhibitor (N-acetyl- l -cysteine) and autophagy inhibitor (chloroquine), T-12 induced tumor regression was significantly decreased. In conclusion, T-12 is a potent inducer of autophagy-dependent apoptosis in breast cancer cells both in vitro and in vivo and can serve as an important lead in development of new anti-tumor therapy.

Fused triazoloquinolines have been prepared starting from ( E )-3-(2-nitrophenyl)-1-aryl-prop-2-en-1-ones and sugar or benzyl azides in a sequential [3+2] cycloaddition reaction, followed by one pot Pd–C assisted reduction, cyclization and aromatization. The triazolyl fused quinolines with N 1 -glycosyl substituents as unnatural nucleosides have inherent potential to generate a library of compounds for bioevaluations.

An efficient and simple strategy for the synthesis of a diverse range of anthraquinone-based aryl-C-glycosides has been developed. It involves the sequential Diels-Alder reaction and oxidative aromatization with the preformed glycosyl diene and dienophiles. The glycosyl dienes were obtained from simple sugars by tandem one-pot substitution and elimination reaction.

Chemoselective reduction of nitro group in polyfunc tional nitrophenyl 2-oxobut-3-enyl C- glycopyranosides to the respective aminophenyl 2-ox obut-3-enyl glycopyranosides with SnCl 2.2H 2O under ultrasonic vibration in good yields was ach ieved successfully. Other potentially reducible groups such as carbonyl, este r, azide, tosyl, alkenic substituents were unaffected during reaction. The 2 '-nitrophenyl-2-oxobut-3-enyl glycopyranosides as re duction substrates gave 2-quinolinemethyl glycopyranosides via reduction followed by intramolecular cyclocondensation reactions. These β-C-glycopyranosides hold great promise in medicinal chemistry.

A new approach to synthesize a homologous series of 14-, 15-, and 16-membered drug-like, macrocyclic glycoconjugates involving TBAHS promoted azide-propenone intramolecular cycloaddition in designed C-glycopyranosyl butenones from a simple sugar d-glucose and d-mannose is reported.

A series of 4-alkylaminoaryl phenyl cyclopropyl methanones (6a–6u and 8a–8c) were synthesized from 4-fluorochalcones (3a and 3b) by cyclopropanation of double bond followed by nucleophilic substitution of F with different amines. The compounds were screened for their antitubercular and antimalarial activities against Mycobacterium tuberculosis H37Rv and Plasmodium falciparum 3D7 strains in vitro respectively. Several compounds (6a, 6d–6h, 6p, 6q and 8a–8c) exhibited good in vitro antitubercular activities with MIC values 3.12–12.5 μg/mL and preferentially inhibited the growth of P. falciparum in vitro (4a, 4c, 6a–6d, 6f, 6s, 8a and 8c) with IC50 as low as 0.080 and 0.035 μg/mL and SI values 4975 and 6948, respectively. Molecular docking studies and in vitro evaluation against FAS-II enzymes using reporter gene assays were carried out to elucidate the mode of action of these molecules. Two compounds 4a and 6g showed significant inhibition at 25 μM concentration of the compound.