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Nitric oxide (NO) is a well-accepted signaling molecule that has regulatory effects on plants under various stresses. Salinity is a major issue that adversely affects plant growth and productivity. The current study was carried out to investigate changes in the growth, biochemical parameters, and yield of wheat plants in response to NO donors, namely sodium nitroprusside (SNP) (2.5 and 5.0 mM) and arginine (10 and 20 mM), under two salinity levels (1.2 mM and 85.5 mM NaCl). Salinity stress significantly decreased the lengths and weights of plant parts (shoot, tiller, and root) and reduced the flag leaf area, photosynthetic pigments, indole acetic acid (IAA), and yield and its components. Moreover, salt stress induced a significant accumulation of some osmoprotectants (total soluble sugars (TSS) and amino acids, especially proline) and triggered the accumulation of hydrogen peroxide (H2O2) and lipid peroxidation in wheat leaves. In contrast, arginine and SNP treatments significantly mitigated the negative impacts of salinity on growth and productivity via enhancing photosynthetic pigments, nitrate reductase, phenolic compounds, IAA, TSS, free amino acids, and proline. In addition, SNP and arginine potentially reduced oxidative damage by decreasing H2O2 and lipid peroxidation through the induction of antioxidant enzymes. The individual amino acid composition of wheat grains under the interactive effect of salinity and NO sources has been scarcely documented until now. In this study, the NO sources restrained the reduction in essential amino acids (isoleucine and lysine) of wheat grains under salinity stress and further stimulated the contents of non-essential and total aromatic amino acids. Interestingly, the applied protectants recovered the decrease in arginine and serine induced by salinity stress. Thus, SNP or arginine at the levels of 5.0 and 20 mM, respectively, had a profound effect on modulating the salt stress of wheat throughout the life cycle.

Hepatitis C virus (HCV) is an international challenge. Since the discovery of NS5A direct-acting antivirals, researchers turned their attention to pursue novel NS5A inhibitors with optimized design and structure. Herein we explore highly potent hepatitis C virus (HCV) NS5A inhibitors; the novel analogs share a common symmetrical prolinamide 2,7-diaminofluorene scaffold. Modification of the 2,7-diaminofluorene backbone included the use of (S)-prolinamide or its isostere (S,R)-piperidine-3-caboxamide, both bearing different amino acid residues with terminal carbamate groups. Compound 26 exhibited potent inhibitory activity against HCV genotype (GT) 1b (effective concentration (EC50) = 36 pM and a selectivity index of >2.78 × 106). Compound 26 showed high selectivity on GT 1b versus GT 4a. Interestingly, it showed a significant antiviral effect against GT 3a (EC50 = 1.2 nM). The structure-activity relationship (SAR) analysis revealed that picomolar inhibitory activity was attained with the use of S-prolinamide capped with R- isoleucine or R-phenylglycine residues bearing a terminal alkyl carbamate group.

One of the major etiological factors that account for lung cancer is tobacco use. Benzo(a)pyrene [B(a)P], one of the main constituents of tobacco smoke, has a key role in lung carcinogenesis. The present study was conducted to investigate the cytotoxicity of an aqueous ethanolic extract of Lagerstroemia speciosa (L.) Pers leaves (LLE) on human lung adenocarcinoma cells (A549), as well as its in vivo antitumor effect on a lung tumorigenesis mice model. Our results revealed that LLE possesses cytotoxic activity against the A549 cell line. Mice orally administered B(a)P (50 mg/kg body weight) showed an increase in relative lung weight with subsequent decrease in final body weight. Serum levels of tumor marker enzymes AHH, ADA and LDH and the inflammatory mediator NF-κB increased, while total antioxidant capacity (TAC) decreased. In addition, we observed the increased activity of metalloproteinases (MMP-2 and MMP-12) and levels of the tumor angiogenesis marker VEFG and the lipid peroxidation marker MDA, as well as decreased levels of the non-enzymatic antioxidant GSH and enzymatic antioxidants CAT and GSH-Px in lung tissues. Moreover, B(a)P administration up-regulated the expression of the COX-2 gene, pro-inflammatory cytokines TNF-α and IL-6, and an anti-apoptotic gene Bcl-2, and at the same time down-regulated expression of pro-apoptotic genes BAX and caspase-3 and the p53 gene. Pre- and post-treatment with LLE (250 mg/kg body weight) attenuated all these abnormalities. Histopathological observations verified the protective effect of LLE. Overall, the present data positively confirm the potent antitumor effect of L. speciosa leaves against lung tumorigenesis.