Bio-molecule functionalized rapid one-pot green synthesis of silver nanoparticles and their efficacy toward the multidrug resistant (MDR) gut bacteria of silkworms (Bombyx mori)

The present study aimed to synthesise bio-molecule functionalized silver nanoparticles (AgNPs) using leaf extract from mulberry variety S-1635 (Morus alba L.) and to explore its antibacterial efficacy against multidrug resistant (MDR) gut bacteria isolated from natural infection observed from silkworm larvae in rearing conditions. AgNPs formation was established by surface plasmon resonance at 480 nm. The crystallinity of the synthesised AgNPs was checked by HR-TEM and XRD analysis. SEM and TEM characterisation further exhibited the spherical, monodispersed, well scattered nature of the AgNPs with an average particle size of 11.8 nm ± 2.8. The presence of (111), (200), (220) and (311) planes in Bragg''s reflections confirmed the face-cantered-cubic crystalline silver. EDX analysis confirmed the presence of elemental silver. FT-IR spectra revealed functional groups were responsible for the reduction of silver ions. The zeta potential value of −17.3 mV and −25.6 mV was recorded in MH and DMEM/F-12 media, respectively. The LC-QTOF/MS and HRMS spectra disclosed the presence of bioactive compounds like flavonoid, gallic acid, and stigmasterol, which are probably involved in the reduction and functionalization of AgNPs. The antibacterial efficacy of bio-molecule functionalized AgNPs and the naked AgNPs was tested on Gram-positive and Gram-negative bacteria isolated from silkworms and characterized by using 16S rDNA and gyrB genes. The cytotoxicity of AgNPs was tested on WRL-68, HEK-293, ACHN, and HUH-7 cell lines using MTT assay. This study provides an insight into the application of bio-molecule functionalized AgNPs for combating various silkworm pathogens which severely affect the agro-rural economy of developing countries.

We aimed to synthesise bio-molecule functionalized silver nanoparticles using leaf extract from mulberry variety S-1635 (Morus alba L.) and to explore its antibacterial effect on multidrug resistant gut bacteria isolated from natural infection observed from silkworm larvae.     

A key role of toll-like receptor 3 in tissue factor activation through extracellular signal regulated kinase 1/2 pathway in a murine hypoxia model

Hypoxemia in the circulation can lead to venous thrombosis (VT) through tissue factor (TF) activation, but the mechanism of TF activation in hypoxia remains obscure. Ligands released from damaged tissues or cells due to hypoxia are identified by various pattern-recognition receptors (PRR), including Toll-like receptor3 (TLR3). In the present study, we investigated the mechanism of TF activation during acute hypoxia in a rat model. The expression of TLR3 and TF was analyzed by immunoblotting and RT-PCR. The TF activity was evaluated by two-stage chromogenic assay and fibrin deposition was detected by immunohistochemistry. The expression of TLR3, TF, and TF activity was increased significantly 6 h post acute hypoxia and then decreased gradually. The contribution of TLR3 in TF activation was investigated by poly I:C and TLR3 neutralizing antibody. We also found increased ERK phosphorylation both in acute hypoxia and poly I:C treatment. We further showed that the pre-treatment of TLR3 neutralizing antibody or ERK inhibitor (PD98059) 2 h prior to acute hypoxia or poly I:C treatment completely abrogated ERK phosphorylation and TF activation. The pre-treatment of TLR3 neutralizing antibody also inhibited fibrin deposition in lung vasculature. These data indicate that acute hypoxia induced TF activation is mediated through TLR3-ERK1/2 pathway.     

The use of neem for controlling gastric hyperacidity and ulcer

H₂‐receptor blockers and proton pump inhibitors are now used extensively to control gastric and duodenal ulcer, inflammation and pain, but these drugs have limitations and are not always affordable. The development of novel nontoxic antiulcer drugs, including from medicinal plants, is therefore desirable, and Azadirachta indica A. Juss, commonly known as Neem, is known to have potent gastroprotective and antiulcer effects. This review deals with the pharmacological and biochemical studies carried out regarding the antiulcer activities of Neem extracts and their mechanism of action, including the inhibition of acid secretion. A comparison with ranitidine and omeprazole in some animal models has been included and clinical studies, where available, have also been incorporated, along with a safety evaluation. Neem bark extract has the potential for the development of novel medicines for the therapeutic control of gastric hyperacidity and ulcer. Copyright © 2009 John Wiley & Sons, Ltd.     

Structure-based design and synthesis of a novel long-chain 4′′-alkyl ether derivative of EGCG as potent EGFR inhibitor: in vitro and in silico studies

Herein, we report the discovery of a novel long-chain ether derivative of (−)-epigallocatechin-3-gallate (EGCG), a major green tea polyphenol as a potent EGFR inhibitor. A series of 4′′-alkyl EGCG derivatives have been synthesized via regio-selectively alkylating the 4′′ hydroxyl group in the D-ring of EGCG and tested for their antiproliferative activities against high (A431), moderate (HeLa), and low (MCF-7) EGFR-expressing cancer cell lines. The most potent compound, 4′′-C₁₄ EGCG showed the lowest IC₅₀ values across all the tested cell lines. 4′′-C₁₄ EGCG was also found to be significantly more stable than EGCG under physiological conditions (PBS at pH 7.4). Further western blot analysis and imaging data revealed that 4′′-C₁₄ EGCG induced cell death in A431 cells with shrunken nuclei, nuclear fragmentation, membrane blebbing, and increased population of apoptotic cells where BAX upregulation and BCL_XL downregulation were observed. In addition, autophosphorylation of EGFR and its downstream signalling proteins Akt and ERK were markedly inhibited by 4′′-C₁₄ EGCG. MD simulation and the MM/PBSA analysis disclosed the binding mode of 4′′-C₁₄ EGCG in the ATP-binding site of EGFR kinase domain. Taken together, our findings demonstrate that 4′′-C₁₄ EGCG can act as a promising potent EGFR inhibitor with enhanced stability.

Among the synthesized 4′′-alkyl EGCG derivatives, 4′′-C₁₄ EGCG inhibited EGF stimulated phosphorylation of EGFR and its downstream signaling pathways, ERK and Akt. 4′′-C₁₄ EGCG showed significantly improved stability than EGCG and induced apoptosis.