RESUMEN
Anti-cancer peptides (ACPs) are short peptides known for their ability to inhibit tumor cell proliferation, migration, and the formation of tumor blood vessels. In this study, we designed ACPs to target receptors often overexpressed in cancer using a systematic in silico approach. Three target receptors (CXCR1, DcR3, and OPG) were selected for their significant roles in cancer pathogenesis and tumor cell proliferation. Our peptide design strategy involved identifying interacting residues (IR) of these receptors, with their natural ligands serving as a reference for designing peptides specific to each receptor. The natural ligands of these receptors, including IL8 for CXCR1, TL1A for DcR3, and RANKL for OPG, were identified from the literature. Using the identified interacting residues (IR), we generated a peptide library through simple permutation and predicted the structure of each peptide. All peptides were analyzed using the web-based prediction server for Anticancer peptides, AntiCP. Docking simulations were then conducted to analyze the binding efficiencies of peptides with their respective target receptors, using VEGA ZZ and Chimera for interaction analysis. Our analysis identified HPKFIKELR as the interacting residues (IR) of CXCR-IL8. For DcR3, we utilized three domains from TL1A (TDSYPEP, TKEDKTF, LGLAFTK) as templates, along with two regions (SIKIPSS and PDQDATYP) from RANKL, to generate a library of peptide analogs. Subsequently, peptides for each receptor were shortlisted based on their predicted anticancer properties as determined by AntiCP and were subjected to docking analysis. After docking, peptides that exhibited the least binding energy were further analyzed for their detailed interaction with their respective receptors. Among these, peptides C9 (HPKFELY) and C7 (HPKFEWL) for CXCR1, peptides D6 (ADSYPQP) and D18 (AFSYPFP) for DcR3, and peptides P19 (PDTYPQDP) and p16 (PDQDATYP) for OPG, demonstrated the highest affinity and stronger interactions compared to the other peptides. Although in silico predictions indicated a favorable binding affinity of the designed peptides with target receptors, further experimental validation is essential to confirm their binding affinity, stability and pharmacokinetic characteristics.
RESUMEN
In this study, endophytic bacteria isolated from root, stem, and leaf tissues of stripe rust-susceptible (Inqilab 91, Galaxy 2013, and 15BT023) and stripe rust-resistant (NARC 2011, Ujala 2015, TW1410) cultivars were identified and characterized. Abundance of endophytes was found in roots as compared with stems and leaves. Resistant and susceptible cultivars significantly differed in abundance of endophytic bacteria. Restriction analysis of 16S rRNA genes amplified from 100 bacterial isolates produced 17 unique patterns. Representatives of each of the 17 unique patterns were sequenced and identified. Among the sequenced bacteria, 8 belonged to Firmicutes, 7 were Proteobacteria, and 2 were Actinobacteria. Most of the isolates have plant growth-promoting properties and a few have the potential of producing hydrolytic enzymes. Two isolates showed significant inhibition of rust spore germination. These endophytic bacteria not only can be helpful in growth-promoting activities but also can assist in biocontrol of stripe rust disease
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Asunto(s)
Endófitos/aislamiento & purificación , Raíces de Plantas/microbiología , Phakopsora pachyrhizi/aislamiento & purificación , ARN Ribosómico 16S/aislamiento & purificación , Bacterias/aislamiento & purificación , ARN Ribosómico 16S/genética , ARN Ribosómico 16S/metabolismo , Firmicutes/aislamiento & purificación , Actinobacteria/enzimología , Actinobacteria/aislamiento & purificación , Esporas Bacterianas/crecimiento & desarrollo , Esporas Fúngicas/aislamiento & purificación , PakistánRESUMEN
Objective:To determine antibiotic resistance patterns and virulence potential ofCampylobacter jejuni (C. jejuni) isolates from clinical human diarrheal infections, cattle and healthy broilers. Methods:Antibiotic sensitivity patterns ofC. jejuni isolates were determined by Kirby Bauer Disc Diffusion assay. These isolates were then subjected to virulence profiling for the detection ofmapA (membrane-associated protein),cadF (fibronectin binding protein),wlaN (beta-1,3-galactosyltransferase) andneuAB (sialic acid biosynthesis gene). FurtherC. jejuni isolates were grouped by random amplification of polymorphic DNA (RAPD) profiling.Results: A total of 436 samples from poultry (n=88), cattle (n=216) and humans (n=132) from different locations were collected. Results revealed percentage ofC. jejuni isolates were 35.2% (31/88), 25.0% (54/216) and 11.3% (15/132) among poultry, cattle and clinical human samples respectively. Antibiotic susceptibility results showed that similar resistance patterns to cephalothin was ie. 87.0%, 87.1% and 89%among humans, poultry and cattle respectively, followed by sulfamethoxazole+trimethoprim 40.0%, 38.7% and 31.0% in humans, poultry and cattle and Ampicillin 40%, 32% and 20% in humans, poultry and cattle respectively. Beta-lactamase activity was detected in 40.00% humans, 20.37% cattle and 32.25% in poultryC. jejuni isolates. CadF andmapA were present in all poultry, cattle and humanC. jejuni isolates,wlaN was not detected in any isolate andneuAB was found in 9/31 (36%) poultry isolates. RAPD profiling results suggested high diversity ofC. jejuni isolates.Conclusions:Detection of multidrug resistantC. jejuni strains from poultry and cattle is alarming as they can be potential hazard to humans. Moreover, predominant association of virulence factors,cadF andmapA (100 % each) inC. jejuni isolates from all sources andneuAB (36%) with poultry isolates suggest the potential source of transmission of diverse types ofC. jejuni to humans.