Synthesis and biological evaluation of nigranoic acid esters as novel human neutrophil elastase inhibitors

<div><p>Human neutrophil elastase (HNE) has been implicated as a major contributor in the pathogenesis of diseases, such as lung disorders and other inflammatory diseases. A series of 12 new nigranoic acid esters were regioselectively synthesised in good yields and evaluated for HNE inhibitory activity. Nigranoic acid exhibited significant inhibitory activity against HNE with the IC₅₀ value of 3.77 μM, and six esters displayed considerable inhibitory effects on HNE with IC₅₀ values in the range of 2.61–8.95 μM. The nigranoic acid esters having phenyls substituted with bromine and trimethoxyls (<b>3h</b> and <b>3b</b>) showed stronger inhibitory activity on HNE than nigranoic acid.</p></div

Downregulation of cancer-associated fibroblast exosome-derived miR-29b-1-5p restrains vasculogenic mimicry and apoptosis while accelerating migration and invasion of gastric cancer cells via immunoglobulin domain-containing 1/zonula occluden-1 axis

Background: Cancer-associated fibroblast (CAF) exosomal miRNAs have gradually a hot spot in cancer therapy. This study mainly explores the effect of CAF-derived exosomal miR-29b-1-5p on gastric cancer (GC) cells. Methods: CAFs and exosomes were identified by Western blot and transmission electron microscopy. CAF-derived exosomes-GC cells co-culture systems were constructed. Effects of CAF-derived exosomal miR-29b-1-5p on GC cells were determined by cell counting kit-8, flow cytometry, wound healing, Transwell assays and Western blot. The relationship between miR-29b-1-5p and immunoglobulin domain-containing 1 (VSIG1) was assessed by TargetScan, dual-luciferase reporter and RNA immunoprecipitation (RIP) experiments. The interaction between VSIG1 and zonula occluden-1 (ZO-1) was detected by co-immunoprecipitation. Expressions of miR-29b-1-5p, VSIG1 and ZO-1 were determined by quantitative real-time PCR. Vascular mimicry (VM) was detected using immunohistochemistry and tube formation assays. Rescue experiments and xenograft tumor assays were used to further determine the effect of CAF-derived exosomal miR-29b-1-5p/VSIG1 on GC. Results: VM structure, upregulation of miR-29b-1-5p, and downregulation of VSIG1 and ZO-1 were shown in GC tissues. MiR-29b-1-5p targeted VSIG1, which interacted with ZO-1. CAF-derived exosomal miR-29b-1-5p inhibitor suppressed the viability, migration, invasion and VM formation, but promoted the apoptosis of GC cells. MiR-29b-1-5p inhibitor increased levels of VSIG1, ZO-1 and E-cadherin, whilst decreasing levels of VE-cadherin, N-cadherin and Vimentin in vitro and in vivo, which however was partially reversed by shVSIG1. Downregulation of CAF-derived exosomal miR-29b-1-5p impeded GC tumorigenesis and VM structure in vivo by upregulating VSIG1/ZO-1 expression. Conclusion: Downregulation of CAF-derived exosomal miR-29b-1-5p inhibits GC progression via VSIG1/ZO-1 axis.</p

Genome-Wide Functional Analysis of Cotton (<i>Gossypium hirsutum</i>) in Response to Drought

<div><p>Cotton is one of the most important crops for its natural textile fibers in the world. However, it often suffered from drought stress during its growth and development, resulting in a drastic reduction in cotton productivity. Therefore, study on molecular mechanism of cotton drought-tolerance is very important for increasing cotton production. To investigate molecular mechanism of cotton drought-resistance, we employed RNA-Seq technology to identify differentially expressed genes in the leaves of two different cultivars (drought-resistant cultivar J-13 and drought-sensitive cultivar Lu-6) of cotton. The results indicated that there are about 13.38% to 18.75% of all the unigenes differentially expressed in drought-resistant sample and drought-sensitive control, and the number of differentially expressed genes was increased along with prolonged drought treatment. DEG (differentially expression gene) analysis showed that the normal biophysical profiles of cotton (cultivar J-13) were affected by drought stress, and some cellular metabolic processes (including photosynthesis) were inhibited in cotton under drought conditions. Furthermore, the experimental data revealed that there were significant differences in expression levels of the genes related to abscisic acid signaling, ethylene signaling and jasmonic acid signaling pathways between drought-resistant cultivar J-13 and drought-sensitive cultivar Lu-6, implying that these signaling pathways may participate in cotton response and tolerance to drought stress.</p> </div

Histogram representation of clusters of orthologous groups (COG) classification.

<p>Histogram representation of clusters of orthologous groups (COG) classification.</p

Data_Sheet_1_Dietary meat mutagens intake and cancer risk: A systematic review and meta-analysis.docx

BackgroundClinical and preclinical studies suggested that certain mutagens occurring as a reaction of creatine, amino acids, and sugar during the high temperature of cooking meat are involved in the pathogenesis of human cancer. Here we conducted a systematic review and meta-analysis to examine whether meat mutagens [PhIP, MeIQx, DiMeIQx, total HCA, and B(a)P] present a risk factor for human cancer.MethodsWe searched the following databases for relevant articles published from inception to 10 Oct 2021 with no language restrictions: Pubmed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Baidu Academic, Zhejiang Digital Library. Two independent researchers screened all titles and obtained eligible texts for further screening. Independent data extraction was conducted, and meta-analysis was carried out using random-effects models to calculate the risk ratio of the meat mutagens exposure.ResultsA total of 1,786,410 participants and 70,653 cancer cases were identified. Among these, there were 12 different types of cancer at various sites, i.e., breast, bladder, colorectal, colon, rectum, prostate, lung, Non-Hodgkin lymphoma, kidney, gastric, esophagus, pancreatic, hepatocellular carcinoma. Cancer risk was significantly increased by intake of PhIP (OR = 1.13;95% CI 1.07–1.21; p ConclusionMeat mutagens of PhIP, MeIQx, DiMeIQx, and total HCA have a positive association with the risk of cancer.Systematic review registration[www.crd.york.ac.uk/prospero], identifier [CRD42022148856].</p

Continually-differentially expressed unigenes at different drought period.

<p>J13-ck, J13-2d, J13-4d, J13-6d and J13-8d refer to control (J13 plants grown under normal conditions) and 2, 4, 6, and 8 days after withholding water of J-13.</p

Gene-specific primers used in real-time quantitative RT-PCR analysis.

<p>Gene-specific primers used in real-time quantitative RT-PCR analysis.</p

Assay of drought resistance of the two cotton cultivars.

<p>(<b>A</b>) Seedlings of the cultivar J-13 in pot after withholding water for 15 days. (<b>B</b>) Seedlings of the cultivar Lu-6 in pot after withholding water for 15 days. (<b>C</b>) The percentage of wilting seedlings after withholding water for 13 and 15 days. J-13, cotton cultivar Jingmian13; Lu-6, cotton cultivar Lumian6.</p

Total number of differentially expressed unigenes (fold change≥2 or ≤0.5).

<p>J13-ck, J13-2d, J13-4d, J13-6d and J13-8d refer to control (J13 plants grown under normal conditions) and 2, 4, 6, and 8 days after withholding water of J-13. Lu 6-6d refers to 6 days after withholding water of Lu-6.</p

GO functional classification of two different samples.

<p>GO functional classification analysis of differentially expressed genes between J-13 and Lu-6 after 6 days of drought treatment. Histograms represent the functional distribution, which is expressed as a percentage of the amount of genes.</p