As a novel type of antibiotic alternative, peptide‐based antibacterial drug shows potential application prospects attributable to their unique mechanism for lysing the membrane of pathogenic bacteria. However, peptide‐based antibacterial drugs suffer from a series of problems, most notably their immature stability, which seriously hinders their application. In this study, self‐assembling chimeric peptide nanoparticles (which offer excellent stability in the presence of proteases and salts) are constructed and applied to the treatment of bacterial infections. In vitro studies are used to demonstrate that peptide nanoparticles NPs1 and NPs2 offer broad‐spectrum antibacterial activity and desirable biocompatibility, and they retain their antibacterial ability in physiological salt environments. Peptide nanoparticles NPs1 and NPs2 can resist degradation under high concentrations of proteases. In vivo studies illustrate that the toxicity caused by peptide nanoparticles NPs1 and NPs2 is negligible, and these nanoparticles can alleviate systemic bacterial infections in mice and piglets. The membrane permeation mechanism and interference with the cell cycle differ from that of antibiotics and mean that the nanoparticles are at a lower risk of inducing drug resistance. Collectively, these advances may accelerate the development of peptide‐based antibacterial nanomaterials and can be applied to the construction of supramolecular nanomaterials.

2021-05-01·The Plant journal : for cell and molecular biology1区 · 生物学

The new kid on the block: a dominant‐negative mutation of phototropin1 enhances carotenoid content in tomato fruits

1区 · 生物学

Article

作者: Sharma, Sulabha ; Dindu, Alekhya ; Nizampatnam, Narasimha Rao ; Dhanya, Ajayakumar Jaya ; Tyagi, Kamal ; Thazath, Nikhil Padmanabhan ; Kilambi, Himabindu Vasuki ; Gupta, Neha ; Sharma, Kapil ; Kumar, Sumit ; Sreelakshmi, Yellamaraju ; Sharma, Rameshwar

SUMMARY:

Phototropins, the UVA‐blue light photoreceptors, endow plants to detect the direction of light and optimize photosynthesis by regulating positioning of chloroplasts and stomatal gas exchange. Little is known about their functions in other developmental responses. A tomato Non‐phototropic seedling1 (Nps1) mutant, bearing an Arg495His substitution in the vicinity of LOV2 domain in phototropin1, dominant‐negatively blocks phototropin1 responses. The fruits of Nps1 mutant were enriched in carotenoids, particularly lycopene, compared with its parent, Ailsa Craig. On the contrary, CRISPR/CAS9‐edited loss of function phototropin1 mutants displayed subdued carotenoids compared with the parent. The enrichment of carotenoids in Nps1 fruits is genetically linked with the mutation and exerted in a dominant‐negative fashion. Nps1 also altered volatile profiles with high levels of lycopene‐derived 6‐methyl 5‐hepten2‐one. The transcript levels of several MEP and carotenogenesis pathway genes were upregulated in Nps1. Nps1 fruits showed altered hormonal profiles with subdued ethylene emission and reduced respiration. Proteome profiles showed a causal link between higher carotenogenesis and increased levels of protein protection machinery, which may stabilize proteins contributing to MEP and carotenogenesis pathways. The enhancement of carotenoid content by Nps1 in a dominant‐negative fashion offers a potential tool for high lycopene‐bearing hybrid tomatoes.

2010-06-01·The Journal of surgical research4区 · 医学

ZM336372 Induces Apoptosis Associated with Phosphorylation of GSK-3β in Pancreatic Adenocarcinoma Cell Lines

4区 · 医学

Article

作者: Herbert Chen ; Peter Geiger ; Dustin Deming ; Muthusamy Kunnimalaiyaan ; Kyle Holen

INTRODUCTION:

ZM336372 is small molecule tyrosine kinase modulator. It has been shown to inhibit glycogen synthase kinase-3beta (GSK-3beta) through phosphorylation of GSK-3beta at Ser 9. GSK-3beta has previously been shown to mediate cell survival in pancreatic cancer cells. Here we determine the effects of ZM336372 on GSK-3beta phosphorylation, apoptosis, and growth in pancreatic adenocarcinoma cell lines.

METHODS:

Panc-1 and MiaPaCa-2 cells were treated with ZM336372 or lithium chloride (LiCl) and compared with solvent control. The effects on proliferation for each cell line were determined using the MTT assay. Western blot analysis was performed to examine the effects of treatment on the phosphorylation of GSK-3beta. In addition, western blot was utilized to examine the cleavage of poly (ADP-ribose) polymerase (PARP), a marker of apoptosis.

RESULTS:

A dose-dependent increase in phosphorylation of GSK-3beta was observed after treatment with both ZM336372 and LiCl. Growth inhibition due to treatment with ZM336372 and LiCl also occurred in a dose-dependent fashion. An increase in cleaved PARP was demonstrated after treatment with both agents, as was seen previously with GSK-3beta inhibition in pancreatic adenocarcinoma cells.

CONCLUSION:

This is the first description of growth inhibition and apoptosis in pancreatic cancer cells related to GSK-3beta inhibition through treatment with ZM336372.

100 项与 NPS-1 相关的药物交易

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