Isolation and biochemical characterization of a novel antimicrobial agent produced by Streptomyces violaceusniger isolated from Yemeni soil

Background: Infections caused by multidrug-resistant bacteria present daily challenges to infectious disease physicians in hospitals throughout the world and these pathogens are spreading into the community. The development of new antibacterial agents to combat worsening antibiotic resistance is still a priority area in anti-infective research.Methods: The experiments were carried out to search for new natural antibiotics through isolation of various Streptomyces strains from different soil samples from Yemen and studying the antimicrobial effects of metabolites that produced. In the same time, the toxicological and biochemical effects of the extracted antibiotic on animals were studied.Results: Streptomyces violaceusniger, was isolated from Yemeni soil sample produced active metabolite that was designated faqihmycin has substantial antimicrobial potential against different microbial species. Investigations into the possible mode of action of faqihmycin revealed that it affects cell wall synthesis and intracellular macromolecule contents of the Gram-positive bacteria Bacillus subtilis. Toxicity studies of faqihmycin confirmed the hepatotoxicity of faqihmycin, there is no strong evidence to suggest that it is nephrotoxic.Conclusions: Further studies with Faqihmycin are needed in order to elucidate its detailed mechanism of action on bacterial cells, as well as studies with Faqihmycin with different doses in order to determine its potential therapeutic use.

In ovo protective effects of chicoric and rosmarinic acids against Thiacloprid-induced cytotoxicity, oxidative stress, and growth retardation on newly hatched chicks

Thiacloprid (TH) is a neonicotinoid insecticide employed in agriculture to protect fruits and vegetables against different insects. It showed different deleterious effects on the general health of non-target organisms including birds and animals, however, its developmental toxicity has yet to be fully elucidated. Chicoric (CA) and rosmarinic (RA) acids are polyphenolic compounds with a wide range of beneficial biological activities. In this study, the possible protective effects of CA and RA were investigated in chick embryos exposed in ovo to TH (1mg/egg) with or without CA (100 mg/egg) or RA (100 mg/egg) co-exposure. TH reduced the hatchling body weight, body weight/egg weight, and relative weight of bursa of Fabricius in the one-day-old hatchlings. Examination of the 7-day-old chicks revealed a decline in feed intake, daily weight gain, feed conversion ratio (FCR), and plasma levels of T3, T4, and growth hormone. Serum ALT, AST activities, and total cholesterol levels showed significant elevations. Hepatic MDA was increased with a reduction in SOD activity and GSH level and downregulation of the liver SOD and GST gene expression pattern. Serum IgG and IgM levels were reduced, and various histopathological alterations were noticed in the liver. Co-administration of CA or RA with TH mitigated the toxic effects on hatchlings. When both CA and RA are combined, they present a synergistic protective effect. CA and RA can be used as protective agents against TH toxicity as they improve growth performance and have hepatoprotective and immunostimulant effects in newly hatched chicks

Isolation and biochemical characterization of a novel antimicrobial agent produced by Streptomyces violaceusniger isolated from Yemeni soil

Background: Infections caused by multidrug-resistant bacteria present daily challenges to infectious disease physicians in hospitals throughout the world and these pathogens are spreading into the community. The development of new antibacterial agents to combat worsening antibiotic resistance is still a priority area in anti-infective research.Methods: The experiments were carried out to search for new natural antibiotics through isolation of various Streptomyces strains from different soil samples from Yemen and studying the antimicrobial effects of metabolites that produced. In the same time, the toxicological and biochemical effects of the extracted antibiotic on animals were studied.Results: Streptomyces violaceusniger, was isolated from Yemeni soil sample produced active metabolite that was designated faqihmycin has substantial antimicrobial potential against different microbial species. Investigations into the possible mode of action of faqihmycin revealed that it affects cell wall synthesis and intracellular macromolecule contents of the Gram-positive bacteria Bacillus subtilis. Toxicity studies of faqihmycin confirmed the hepatotoxicity of faqihmycin, there is no strong evidence to suggest that it is nephrotoxic.Conclusions: Further studies with Faqihmycin are needed in order to elucidate its detailed mechanism of action on bacterial cells, as well as studies with Faqihmycin with different doses in order to determine its potential therapeutic use.

Effects of probiotic feed additives (biosol and Zemos) on growth and related genes in broiler chickens

The goal of this study was to look into the effect of two probiotics as feed additives: Biosol (lipotropic factor containing probiotics) and/or Zemos, and to determine the best regimen for using both probiotics to improve growth performance, carcass traits, blood parameters, and transcription of some growth and immunity-related genes in broiler chickens. A commercial hatchery provided 400 one-day-old Cobb broiler chicks. The chicks were divided into four equal groups at random, each with 100 birds. Group 1 served as a negative control. Group 2 was given Probiotic 1(Biosol) in drinking water at a dose of 120 g/10,000 chick each day. Group 3 received probiotic 2 (Zemos) at a dose of 0.25 mL/L of drinking water for 3 days/week. Group 4 was given combined probiotics (Biosol + Zemos), with the same weekly dose of each probiotic alternatively. During the experiment, all chickens were fed and hydrated ad libitum and exposed to 24 h of light. Our findings revealed that chicks fed on diets supplemented with Biosol and Biosol + Zemos showed an increase in body weight gain and lower feed conversion rates. Total protein levels were elevated while cholesterol and triglyceride levels dropped, whereas, no effect was detected in the uric acid levels among those groups. Furthermore, the carcass traits of Biosol and Biosol + Zemos increased as a result of the dietary supplementations, however, the weight of the drumstick showed no difference among the four groups. Both probiotics influenced the cecal count of lactobacilli, total aerobes, E. coli, and Enterococci in, as well as the transcript levels of the MTOR, SMYD, TLR-4, and NBN genes. It is possible to conclude that supplementing broilers with probiotics and Biosol, in particular, can increase their growth performance, and improve the biochemical characteristics of the blood and transcript levels of the genes under investigation.Highlights Supplementation of the broiler diet with probiotics is essential Biosol and Zemos increased the growth performance Both probiotics improved the biochemical blood parameters Biosol up-regulated growth and immunity related gene

Anti-parasitic activity of garlic (Allium sativum) and onion (Allium cepa) extracts against Dactylogyrus spp. (Monogenean) in Nile tilapia (Oreochromis niloticus): Hematology, immune response, histopathological investigation, and inflammatory cytokine genes of gills

Abstract Background Gills monogenean infestation causes significant mortalities in cultured fishes as a result of respiratory manifestation. Medicinal plants are currently being heavily emphasized in aquaculture due to their great nutritional, therapeutic, antimicrobial activities, and financial value. Methods The current study is designed to assess the effect of garlic (Allium sativum) and onion (Allium cepa) extracts as a water treatment on the hematological profile, innate immunity, and immune cytokines expression besides histopathological features of gills of Nile tilapia (Oreochromis niloticus L.) infected with gills monogenetic trematodes (Dactylogyrus sp.). Firstly, the 96-hour lethal concentration 50 (96 h-LC50) of garlic extract (GE) and onion extract (OE) were estimated to be 0.4 g/ L and 3.54 g/ L for GE and OE, respectively. Moreover, the in-vitro anti-parasitic potential for (GE) was found between 0.02 and 0.18 mg/mL and 0.4 to 1.8 mg/mL for OE. For the therapeutic trial, fish (n = 120; body weight: 40–60 g) were randomly distributed into four groups in triplicates (30 fish/group, 10 fish/replicate) for 3 days. Group1 (G1) was not infected or treated and served as control. G2 was infected with Dactylogyrus spp. and not exposed to any treatment. G3, G4 were infected with Dactylogyrus sp. and treated with 1/10 and 1/5 of 96 h LC50 of OE, respectively. G5, G6 were infected with Dactylogyrus sp. and treated with 1/10 and 1/5 of 96 h LC50 of GE, respectively. Results No apparent signs or behaviors were noted in the control group. Dactylogyrus spp. infected group suffered from clinical signs as Pale color and damaged tissue. Dactylogyrus spp. infection induced lowering of the hematological (HB, MCH, MCHC and WBCs), and immunological variables (lysozyme, nitric oxide, serum Anti- protease activities, and complement 3). the expression of cytokine genes IL-ß and TNF-α were modulated and improved by treatment with A. sativum and A. cepa extracts. The obtained histopathological alterations of the gills of fish infected with (Dactylogyrus spp.) were hyperplasia leading to fusion of the gill filament, lifting of epithelial tissue, aneurism and edema. The results indecated that G4 and G5 is more regenarated epithelium in compare with the control group. Conclusion A. sativum and A. cepa extracts enhance the blood profile and nonspecific immune parameters, and down-regulated the expression level of (IL-1β and TNF-α)

Synthesis, 3D-QSAR, and Molecular Modeling Studies of Triazole Bearing Compounds as a Promising Scaffold for Cyclooxygenase-2 Inhibition

Targeting of cyclooxygenase-2 (COX-2) has emerged as a powerful tool for therapeutic intervention because the overexpression of this enzyme is synonymous with inflammation, cancer, and neurodegenerative diseases. Herein, a new series of 1,2,4-triazole Schiff bases scaffold with aryl and heteroaryl systems 9a–12d were designed, synthesized, structurally elucidated, and biologically evaluated as a potent COX-2 blocker. The rationale beyond the current study is to increase the molecule bulkiness allowing a selective binding to the unique hydrophobic pocket of COX-2. Among the triazole–thiazole hybrids, the one with the para-methoxy moiety linked to a phenyl ring 12d showed the highest In vitro selectivity by COX-2 inhibition assay (IC50 of 0.04 μM) and in situ anti-inflammatory activity when evaluated using the protein denaturation assay (IC50 of 0.88 μM) in comparison with commercially available selective COX-2 inhibitor, Celecoxib (IC50 of 0.05 μM). Towards the COX-2 selectivity, ligand-based three dimensional quantitative structures activity relationship (3D-QSAR) employing atomic-based and field-based approaches were performed and resulted in the necessity of triazole and thiazole/oxazole scaffolds for COX-2 blocking. Furthermore, the molecular modeling study indicated a high selectivity and promising affinity of our prepared compounds to COX-2, especially the hydrophobic pocket and the mouth of the active site holding hydrogen-bonding, hydrophobic, and electrostatic interactions. In Silico absorption, delivery, metabolism, and excretion (ADME) predictions showed that all the pharmacokinetic and physicochemical features are within the appropriate range for human use

Adaptive Responses of Four Medicinal Plants to High Altitude Oxidative Stresses through the Regulation of Antioxidants and Secondary Metabolites

The conservation of medicinal plants, particularly endangered or endemic species, is of the utmost importance, especially in light of inevitable climate change and its consequences. Species inhabiting high altitudes adopt exceptional defense mechanisms in response to abiotic stresses as a survival strategy. The objective of the current study was to investigate the effects of altitudinal variations on secondary metabolite accumulation and antioxidant enzyme capacity in four plants (Cotoneaster orbicularis, Crataegus x sinaica, Echinops spinosissimus subsp. Spinosissimus, and Tanacetum sinaicum) growing naturally on the Sinai Peninsula’s high mountains. Plant leaves and soil samples were collected from three altitudes between 1500 and 2250 m a.s.l. to evaluate the adaptive responses of these species in relation to high-altitude oxidative stresses. The results showed that at higher altitudes, the electrical conductivity and the micronutrient contents of the soil decreased, which may be due to the prevalence of silt and clay decreasing at higher altitudes. Chlorophyll a, chlorophyll b, ascorbic acid, and total soluble protein showed similar results in relation to higher altitudes for all species. On the other hand, proline, total soluble sugars, carotenoids, phenols, tannins, and flavonoids increased in response to high altitudes. The activity levels of catalase and ascorbic acid peroxidase showed a significant increase aligned with higher altitudes, while a significant decrease in activity levels was obtained for polyphenol oxidase. In conclusion, the present findings showed that Cotoneaster orbicularis exhibited the maximum response for coping with high-altitude stresses, followed by the remaining three species regarding the level of biochemical and physiological responses. The present work will help formulate conservation plans for important medicinal species

Discovery of Potent Dual EGFR/HER2 Inhibitors Based on Thiophene Scaffold Targeting H1299 Lung Cancer Cell Line

Dual targeting of epidermal growth factor receptor (EGFR) and human EGFR-related receptor 2 (HER2) is a proven approach for the treatment of lung cancer. With the aim of discovering effective dual EGFR/HER2 inhibitors targeting non-small cell lung cancer cell line H1299, three series of thieno[2,3-d][1,2,3]triazine and acetamide derivatives were designed, synthesized, and biologically evaluated. The synthesized compounds displayed IC50 values ranging from 12 to 54 nM against H1299, which were superior to that of gefitinib (2) at 40 µM. Of the synthesized compounds, 2-(1H-pyrazolo[3,4-b]pyridin-3-ylamino)-N-(3-cyano4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)acetamide (21a) achieved the highest in vitro cytotoxic activity against H1299, with an IC50 value of 12.5 nM in situ, and 0.47 and 0.14 nM against EGFR and HER2, respectively, values comparable to the IC50 of the approved drug imatinib (1). Our synthesized compounds were promising, demonstrating high selectivity and affinity for EGFR/HER2, especially the hinge region forming a hydrophobic pocket, which was mediated by hydrogen bonding as well as hydrophobic and electrostatic interactions, as indicated by molecular modeling. Moreover, the designed compounds showed good affinity for T790M EGFR, one of the main mutants resulting in acquired drug resistance. Furthermore, both pharmacokinetic and physicochemical properties of the designed compounds were within the appropriate range for human usage as predicted by the in Silico ADME study. The designed compound (21a) might serve as an encouraging lead compound for the discovery of promising anti-lung cancer agents targeting EGFR/HER2

Investigating the Phenotypic Plasticity of the Invasive Weed <i>Trianthema portulacastrum</i> L.

Phenotypic plasticity is frequently highlighted as a key factor in plant invasiveness, as it enables invasive species to adapt to diverse, complicated habitats. Trianthema portulacastrum is one of the most common aggressive species that threaten different crops around the world. Phenotypic plasticity in T. portulacastrum was investigated by comparing variation in germination, vegetative macromorphology, photosynthetic pigments, stomatal complexes, and seed micromorphological traits of 35 samples collected from 35 different localities. One-way cluster analysis and principal component analysis (PCA) were used to classify samples into homogeneous groups based on the measured traits. Pairwise statistical comparisons were conducted between the three resulting groups. The phenotypic plasticity index (PI) was calculated and compared among different groups of characters. Results showed that photosynthetic pigments and macromorphological characteristics had the highest PI, followed by seed micromorphology, and then stomatal complex traits, while germination parameters showed the lowest PI. We propose that soil moisture, salinity, and temperature are the most determinative and explanative variables of the variation between the three classified groups. We strongly believe that the phenotypic plasticity of T. portulacastrum will support species abundance and spread even under expected changes in climatic conditions, in contrast to the vulnerable traditional crops