Prevalence, genetic diversity, and antimicrobial susceptibility of Vibrio spp. infected gilthead sea breams from coastal farms at Damietta, Egypt.

BACKGROUND: Vibriosis is one of the most serious bacterial diseases and causes high morbidity and mortality among cultured sea breams. This study was undertaken to track the surveillance of Vibrio infection and its correlation to environmental factors. A total of 115 gilthead sea breams were collected seasonally from a private earthen pond fish farm in the Shatta area of Damietta, Egypt from September 2022 to July 2023. Physicochemical parameters of water were analyzed, and heavy metal levels were measured. The fish samples were subjected to clinical, bacteriological, Enterobacterial Repetitive Intergenic Consensus (ERIC) fingerprinting, and hematoxylin and Eosin histopathological staining. RESULTS: The results revealed significant variations in the water quality parameters over different seasons, in addition to an increase in heavy metals. Naturally infected fish showed external signs and postmortem lesions that were relevant to bacterial infection. Two dominant Vibrio subspecies of bacteria were identified: V. alginolyticus (205 isolates) and V. fluvialis (87 isolates). PCR confirmed the presence of V. alginolyticus using the species-specific primer collagenase at 737 bp. The highest prevalence of V. alginolyticus was detected during the summer season (57.72%), and the lowest prevalence was observed in autumn (39.75%). The correlation analysis revealed a positive relationship between V. alginolyticus and water temperature (r = 0.69). On the other hand, V. fluvialis showed a high prevalence during the autumn season (25.30%) and the lowest prevalence during the summer season (10.56%), where it was negatively correlated with water temperatures (r =-0.03). ERIC fingerprinting showed genetic variation within the Vibrio isolates. Antimicrobial susceptibility testing revealed sensitivity to ciprofloxacin and doxycycline, and resistance to amoxicillin and erythromycin. The multiple antibiotic resistance (MAR) index values for V. alginolyticus and V. fluvialis ranged from 0.3 to 0.7, with a multi-drug resistance pattern to at least three antibiotics. Histopathological alterations in the affected tissues revealed marked hemorrhage, vascular congestion, and hemosiderosis infiltration. CONCLUSION: This study provides insights into the potential propagation of waterborne diseases and antibiotic resistance in the environment. Ensuring that the environment does not serve as a reservoir for virulent and contagious Vibrio species is a critical concern for regional aquaculture industries. Therefore, we recommend implementing environmental context-specific monitoring and surveillance tools for microbial resistance.

Wound healing potential of Cystoseira/mesenchymal stem cells in immunosuppressed rats supported by overwhelming immuno-inflammatory crosstalk.

Wound healing, one of the most intricate and dynamic processes of the body, maintains skin integrity following trauma. One of the main issues that still exists is impaired wound healing, particularly for immunosuppressed patients. Recently, natural products from marine environments have been employed in wound-repairing activities. This work investigates the mesenchymal stem cells in the combined capacity of the bone marrow (BMMSC) for wound healing and Cystoseira sp. Algae extract in immunosuppressed rats. High-resolution liquid chromatography / MS investigation of Cystoseira extract revealed the prevalence of fatty acids that have wound-soothing potential. From constructed PPI network for wound healing and further analysis through molecular docking and molecular dynamics (MD) simulation experiments suggested that cystalgerone metabolite may be responsible for the wound healing-promoting effect of Cystoseira extract. According to the CD marker characterization of the BMMSC, 98.21% of them expressed CD90, and 97.1% expressed CD105. Sixteen d after immunity suppression (by 40 mg/kg hydrocortisone daily), an incision was made in the dorsal skin of the rat. The treatments were applied for 16 d and samples were taken from the tested groups on the 8th, 14th, and 16th days. The BMMSCs / Cystoseira group showed significantly improved wound closure, thickness, density of new layers, and skin elasticity than the control group (p < 0.001). The BMMSCs / Cystoseira combination significantly reduced the oxidative indicators, pro-inflammatory cytokines, and immune markers, according to the RT-PCR gene expression study. In order to delve deeper into the complex interconnections among wound healing-related biological targets and pinpoint key factors in this complex process, we engaged in network pharmacology and computational research. Subsequently, we conducted a comprehensive computational analysis, including reverse docking, free energy (ΔG) computation, and molecular dynamics simulations, on the molecular structures of the annotated compounds. The purpose of this investigation was to identify potential new targets for these chemicals as well as any potential interactions they may have with different signaling pathways related to the wound healing process. Our research indicates that the primary compounds of Cystoseira holds potential wound healing therapeutic activity. Although more safety testing and clinical studies are required, the combination has great potential for regenerative medicine and could be a revolutionary advance in the healing of the wounds of immunosuppressed patients.

Dietary microalgal-fabricated selenium nanoparticles improve Nile tilapia biochemical indices, immune-related gene expression, and intestinal immunity.

BACKGROUND: Feed supplements, including essential trace elements are believed to play an important role in augmenting fish immune response. In this context, selenium nanoparticles (SeNPs) in fish diets via a green biosynthesis strategy have attracted considerable interest. In this investigation, selenium nanoparticles (SeNPs, 79.26 nm) synthesized from the green microalga Pediastrum boryanum were incorporated into Nile tilapia diets to explore its beneficial effects on the immune defense and intestinal integrity, in comparison with control basal diets containing inorganic Se source. Nile tilapia (No. 180, 54-57 g) were fed on three formulated diets at concentrations of 0, 0.75, and 1.5 mg/kg of SeNPs for 8 weeks. After the trial completion, tissue bioaccumulation, biochemical indices, antioxidant and pro-inflammatory cytokine-related genes, and intestinal histological examination were analyzed. RESULTS: Our finding revealed that dietary SeNPs significantly decreased (P < 0.05) serum alkaline phosphatase (ALP), lactate dehydrogenase (LDH), and cholesterol, while increasing (P < 0.05) high-density lipoproteins (HDL). The Se concentration in the muscle tissues showed a dose-dependent increase. SeNPs at a dose of 1.5 mg/kg significantly upregulated intestinal interleukin 8 (IL-8) and interleukin 1 beta (IL-1ß) gene transcription compared with the control diet. Glutathione reductase (GSR) and glutathione synthetase (GSS) genes were significantly upregulated in both SeNPs-supplemented groups compared with the control. No apoptotic changes or cell damages were observed as indicated by proliferating cell nuclear antigen (PCNA) and caspase-3 gene expression and evidenced histopathologically. SeNPs supplementation positively affects mucin-producing goblet cells (GCs), particularly at dose of 1.5 mg/kg. CONCLUSION: Therefore, these results suggest that Green synthesized SeNPs supplementation has promising effects on enhancing Nile tilapia immunity and maintaining their intestinal health.

Toxicity Evaluation, Oxidative, and Immune Responses of Mercury on Nile Tilapia: Modulatory Role of Dietary Nannochloropsis oculata.

The current study evaluated the potential ameliorative effect of a dietary immune modulator, Nannochloropsis oculata microalga, on the mercuric chloride (HgCl2)-induced toxicity of Nile tilapia. Nile tilapia (45-50 g) were fed a control diet or exposed to » LC50 of HgCl2 (0.3 mg/L) and fed on a medicated feed supplemented with N. oculata (5% and 10% (50 or 100 g/kg dry feed)) for 21 days. Growth and somatic indices, Hg2+ bioaccumulation in muscles, and serum acetylcholinesterase (AChE) activity were investigated. Antioxidant and stress-related gene expression analyses were carried out in gills and intestines. Histopathological examinations of gills and intestines were performed to monitor the traits associated with Hg2+ toxicity or refer to detoxification. Hg2+ toxicity led to significant musculature bioaccumulation, inhibited AChE activity, downregulated genes related to antioxidants and stress, and elicited histopathological changes in the gills and intestine. Supplementation with N. oculata at 10% was able to upregulate the anti-oxidative-related genes while downregulated the stress apoptotic genes in gills and intestines compared to the unexposed group. In addition, minor to no histopathological traits were detected in the gills and intestines of the N. oculata-supplemented diets. Our data showed the benefit of dietary N. oculata in suppressing Hg2+ toxicity, which might support its efficacy as therapeutic/preventive agent to overcome environmental heavy metal pollution in aquatic habitats.

Egyptian mandarin peel oil's anti-scabies potential via downregulation-of-inflammatory/immune-cross-talk: GC-MS and PPI network studies.

The current study investigated the scabicidal potential of Egyptian mandarin peel oil (Citrus reticulata Blanco, F. Rutaceae) against sarcoptic mange-in-rabbits. Analysis of the oil's GC-MS identified a total of 20 compounds, accounting for 98.91% of all compounds found. Mandarin peel oil topical application improved all signs of infection, causing a scabicidal effect three days later, whereas in vitro application caused complete mite mortality one day later. In comparison to ivermectin, histopathological analysis showed that the epidermis' inflammatory-infiltration/hyperkeratosis-had disappeared. In addition to TIMP-1, the results of the mRNA gene expression analysis showed upregulation of I-CAM-1-and-KGF and downregulation of ILs-1, 6, 10, VEGF, MMP-9, and MCP-1. The scabies network was constructed and subjected to a comprehensive bioinformatic evaluation. TNF-, IL-1B, and IL-6, the top three hub protein-coding genes, have been identified as key therapeutic targets for scabies. From molecular docking data, compounds 15 and 16 acquired sufficient affinity towards the three screened proteins, particularly both possessing higher affinity towards the IL-6 receptor. Interestingly, it achieved a higher binding energy score than the ligand of the docked protein rather than displaying proper binding interactions like those of the ligand. Meanwhile, geraniol (15) showed the highest affinity towards the GST protein, suggesting its contribution to the acaricidal effect of the extract. The subsequent, MD simulations revealed that geraniol can achieve stable binding inside the binding site of both GST and IL-6. Our findings collectively revealed the scabicidal ability of mandarin peel extract for the first time, paving the way for an efficient, economical, and environmentally friendly herbal alternative for treating rabbits with Sarcoptes mange.

Host-pathogen interaction unveiled by immune, oxidative stress, and cytokine expression analysis to experimental Saprolegnia parasitica infection in Nile tilapia.

The present study evaluated the pathogenicity, immunological, and oxidant/antioxidant responses against Saprolegnia parasitica (S. parasitica) infection in Nile tilapia (Oreochromis niloticus). Three groups of Nile tilapia were assigned as the control group (no zoospores exposure). The other two groups were challenged by Saprolegnia zoospores; one was used for sampling, and the other for mortality monitoring. The study lasted 3 weeks and was sampled at three point times at 1, 2, and 3 weeks. Results showed that S. parasitica zoospores were pathogenic to Nile tilapia, causing a cumulative mortality rate of 86.6%. Immunoglobulin M and C- reactive protein (IgM and CRP) levels showed a similar trend being significantly (P < 0.05, P < 0.001) higher in the infected group at weeks 1, 2, and 3, respectively, compared to the control group. Oxidant and antioxidant parameters in gills revealed that Malondialdehyde (MDA) level was significantly higher in the infected group compared to the control group. While catalase, glutathione peroxidase, and superoxide dismutase (CAT, GSH, and SOD) levels were significantly decreased in the infected group compared to the control group. Compared to the control, the tumor necrosis factor-α (TNF-α) gene was firmly upregulated in gill tissue at all-time points, particularly at day 14 post-infection. Meanwhile, Interleukin 1-ß (IL-1 ß) gene was significantly upregulated only at days 7 and 14 post-infection compared to control. Histopathological examination revealed destructive and degenerative changes in both skin and gills of experimentally infected Nile tilapia. Our findings suggest that Nile tilapia-S. parasitica infection model was successful in better understanding of pathogenicity and host (fish)-pathogen (oomycete) interactions, where the induced oxidative stress and upregulation of particular immune biomarkers in response to S. parasitica infection may play a crucial role in fish defense against oomycetes in fish.

Wound Restorative Power of Halimeda macroloba/ Mesenchymal Stem Cells in Immunocompromised Rats via Downregulating Inflammatory/Immune Cross Talk.

Impaired skin wound healing is still a major challenge, especially with immunocompromised patients who express delayed healing and are susceptible to infections. Injection of rat-derived bone marrow mesenchymal stem cells (BMMSCs) via the tail vein accelerates cutaneous wound healing via their paracrine activity. The present work aimed to investigate the combined wound-healing potential of BMMSCs and Halimeda macroloba algae extract in immunocompromised rats. High-resolution liquid chromatography-mass spectrometry (HR-LC-MS) investigation of the extract revealed the presence of variant phytochemicals, mostly phenolics, and terpenoids, known for their angiogenic, collagen-stimulating, anti-inflammatory, and antioxidant properties. The BMMSCs were isolated and characterized for CD markers, where they showed a positive expression of CD90 by 98.21% and CD105 by 97.1%. Twelve days after inducing immunocompromise (40 mg/kg hydrocortisone daily), a circular excision was created in the dorsal skin of rats and the treatments were continued for 16 days. The studied groups were sampled on days 4, 8, 12, and 16 after wounding. The gross/histopathological results revealed that the wound closure (99%), thickness, density of new epidermis and dermis, and skin elasticity in the healed wounds were considerably higher in the BMMSCs/Halimeda group than the control group (p < 0.05). RT-PCR gene expression analysis revealed that the BMMSCs/Halimeda extract combination had perfectly attenuated oxidative stress, proinflammatory cytokines, and NF-KB activation at day 16 of wounding. The combination holds promise for regenerative medicine, representing a revolutionary step in the wound healing of immunocompromised patients, with still a need for safety assessments and further clinical trials.

Nutritional and immunological evaluation of Nannochloropsis oculata as a potential Nile tilapia-aquafeed supplement.

Nannochloropsis oculata (N. oculata) is a marine microalga containing bioactive compounds and a high omega-3 polyunsaturated fatty acid (ω-3 PUFAs). Therefore, it is very promising for nutraceutical and the functional food industry applications. Three groups of Nile tilapia (forty-five fish/group) were fed on basal diets or diets containing 5% (N5) or 10% (N10) of the microalga N. oculata for seven weeks. Fish growth performance, proximate composition, and lipid (fatty acids/ FAs and lipoproteins) profile were estimated. In addition, the expression pattern of some lipid metabolism and immune-relevant genes were assessed. An enhancement in whole body crude protein and growth indices of Nile tilapia was observed on both the supplemented groups N5 and N10. Higher levels of high-density lipoproteins (HDL); and lower levels of the low-density lipoproteins (LDL) were evident in both supplemented groups, while the cholesterol and triglycerides (TG) levels were similar among groups. Ω-3 PUFAs were the significant FAs profile of tilapia fed on N. oculata-supplemented diets in terms of eicosapentaenoic acid, docosahexaenoic acid, and n3/n6 ratio. Concerning the gene expression pattern, heat-shock protein70, glutathione-S-transferase, glutathione peroxidase, and interleukin-1ß (IL-1ß) were elevated significantly in both supplemented groups. IL-10 is only upregulated in the N10 group. The lipid metabolism-related gene expression showed downregulation of only fatty acid synthase (FAS) in both supplemented groups, with no statistical changes in Peroxisome proliferator-activated receptor alpha (PPARα). Tumor necrosis factor-α (TNF-α), Transforming growth factor-ß1 (TGF-ß1), and the apoptotic related genes [caspase3 and Proliferating cell nuclear antigen (PCNA)] showed insignificant changes among groups. The histopathological examination of the intestine, liver, and spleen supports our findings and confirms the benefits and safeness of N. oculata dietary inclusion. Collectively, N. oculata is a very promising nutraceutical for improving fish health and sustainability of aquaculture production.

Nannochloropsis oculata supplementation improves growth, immune response, intestinal integrity, and disease resistance of Nile Tilapia.

OBJECTIVE: The current study evaluated the potential roles of incorporating Nannochloropsis oculata into the diet of Nile Tilapia Oreochromis niloticus in an 8-week trial. METHODS: Dietary supplementation of N. oculata was tested at inclusion levels (0% [control], 5% [N5], and 10% [N1]) in triplicate. After the trial, comprehensive fish health indicators were evaluated. RESULT: N. oculata-supplemented feed had a stimulatory effect on fish body weight, where a significant increase in final weight and specific growth rate was observed in the N10 group compared to the control. Better feed conversion was observed at N5 and N10 compared to control. Organosomatic indices were elevated significantly in the N5 group compared to the N10 and control groups. Serum lysozyme activity was significantly increased in the N10 group compared to N5 and control groups. Levels of IgM were significantly higher in N10 compared to the control and N5 groups, with no significance between the latter. Amylase activity showed a significant enhancement in N10 compared to N5. Both levels of N. oculata preserved hepatic health and antioxidant status. Light and transmission electron microscopy showed that Nile Tilapia fed N. oculata at both levels enhanced intestinal immunity, integrity, and absorptive efficiency. The protecting effect of N. oculata was confirmed against Aeromonas hydrophila challenge, where cumulative mortalities were significantly decreased in N5 and N10 groups compared with the control and more in N10. CONCLUSION: This work confirmed the different beneficial roles of N. oculata dietary supplementation for a Nile Tilapia balanced diet.

Anti-otomycotic potential of nanoparticles of Moringa oleifera leaf extract: an integrated in vitro, in silico and phase 0 clinical study.

Otomycosis is a serious superficial mycotic infection of the outer ear canal caused by some pathogenic species of Candida and Aspergillus. The infection remains a challenge to clinicians owing to the incomplete efficacy of market-available antifungal agents and high recurrence rates. The Moringa oleifera leaf ethanol extract showed efficacy against Candida albicans SC5314, compared to Nystatin® as a reference with MIC values of 7 and 718.33 µg ml-1, respectively. The extract was mixed with lecithin and chitosan to give Moringa core/shell giant nanoparticles, with a good zeta potential (+59.2 mV), a suitable entrapment efficiency (61%) and an enhanced release reaching up to 90% at 8 h. Clinical isolates from oomycote patients were identified via DNA sequencing as Candida parapsilosis, Aspergillus niger and Aspergillus flavus, and the effect of the prepared nanoparticles was tested against them via disk diffusion assay to give inhibition zones of 75, 55 and 55 mm, compared to Nystatin® with 35, 25 and 20 mm, respectively. Interestingly, patients treated with the Moringa-loaded nanoparticles experienced improvement within 1 week with no recurrence for more than 3 months. To have some insight into the bioactive components in the Moringa extract, LC-HRMS-based identification has been employed which led to the annotation of 27 compounds. Subsequent comprehensive in silico investigation suggested some alkaloids to be responsible for the activity targeting the fungal 14-α-demethylase enzyme (CYP51B). Our study revealed that Moringa extract-loaded nanoparticles attained an enhanced antifungal efficacy compared to Nystatin® and therefore they can be employed against invasive and drug-resistant otomycotic infections.

New Halogenated Compounds from Halimeda macroloba Seaweed with Potential Inhibitory Activity against Malaria.

Malaria is one of the most important infectious diseases worldwide. The causative of the most severe forms of malaria, Plasmodium falciparum, has developed resistances against all the available antimalarial drugs. In the present study, the phytochemical investigation of the green seaweed Halimeda macroloba has afforded two new compounds 1-2, along with 4 known ones 3-6. The structures of the compounds had been confirmed using 1& 2D-NMR and HRESIMS analyses. Extensive machine-learning-supported virtual-screening suggested cytochrome-C enzyme as a potential target for compound 2. Docking, absolute-binding-free-energy (ΔGbinding) and molecular-dynamics-simulation (MDS) of compound 2 revealed the strong binding interaction of this compound with cytochrome-C. In vitro testing for crude extract and isolated compounds revealed the potential in vitro inhibitory activity of both extract and compound 2 against P. falciparum. The crude extract was able to inhibit the parasite growth with an IC50 value of 1.8 ± 0.35 µg/mL. Compound 2 also showed good inhibitory activity with an IC50 value of 3.2 ± 0.23 µg/mL. Meanwhile, compound 6 showed moderate inhibitory activity with an IC50 value of 19.3 ± 0.51 µg/mL. Accordingly, the scaffold of compound 2 can be considered as a good lead compound for the future development of new antimalarial agents.

Bioactives and functional food ingredients with promising potential for the management of cerebral and myocardial ischemia: a comprehensive mechanistic review.

Ischemia is a deadly disease featured by restricted perfusion to different organs in the body. An increase in the accumulation of reactive oxygen species and cell debris is the driving force for inducing many oxidative, inflammatory and apoptotic signaling pathways. However, the number of therapeutics existing for ischemic stroke patients is limited and there is insufficient data on their efficiency, which warrants the search for novel therapeutic candidates from natural sources. Herein, a comprehensive survey was done on the reported functional food bioactives (ca. 152 compounds) to manage or protect against health consequences of myocardial and cerebral ischemia. Furthermore, we reviewed the reported mechanistic studies for their anti-ischemic potential. Subsequently, network pharmacology- and in silico-based studies were conducted using the reported myocardial and cerebral ischemia-relevant molecular targets to study their complex interactions and highlight key targets in disease pathogenesis. Subsequently, the most prominent 20 compounds in the literature were used in a comprehensive in silico-based analysis (inverse docking, ΔG calculation and molecular dynamics simulation) to determine other potential targets for these compounds and their probable interactions with different signaling pathways relevant to this disease. Many functional food bioactives, belonging to different chemical classes, i.e., flavonoids, saponins, phenolics, alkaloids, iridoids and carotenoids, were proven to exhibit multifactorial effects in targeting the complex pathophysiology of ischemic conditions. These merits make them valuable therapeutic agents that can outperform the conventional drugs, and hence they can be utilized as add-ons to the conventional therapy for the management of different ischemic conditions; however, their rigorous clinical assessment is necessary.

Antioxidant and Wound Healing Potential of Vitis vinifera Seeds Supported by Phytochemical Characterization and Docking Studies.

This study explored the in vivo wound healing potential of Vitis vinifera seed extract using an excision wound model with focus on wound healing molecular targets including TGFBR1, VEGF, TNF-α, and IL-1ß. The wound healing results revealed that V. vinifera seed extract enhanced wound closure rates (p < 0.001), elevated TGF-ß and VEGF levels, and significantly downregulated TNF-α and IL-1ß levels in comparison to the Mebo®-treated group. The phenotypical results were supported by biochemical and histopathological findings. Phytochemical investigation yielded a total of 36 compounds including twenty-seven compounds (1−27) identified from seed oil using GC-MS analysis, along with nine isolated compounds. Among the isolated compounds, one new benzofuran dimer (28) along with eight known ones (29−36) were identified. The structure of new compound was elucidated utilizing 1D/2D NMR, with HRESIMS analyses. Moreover, molecular docking experiments were performed to elucidate the molecular targets (TNF-α, TGFBR1, and IL-1ß) of the observed wound healing activity. Additionally, the in vitro antioxidant activity of V. vinifera seed extract along with two isolated compounds (ursolic acid 34, and ß-sitosterol-3-O-glucopyranoside 36) were explored. Our study highlights the potential of V. vinifera seed extract in wound repair uncovering the most probable mechanisms of action using in silico analysis.

Multitarget in silico studies of Ocimum menthiifolium, family Lamiaceae against SARS-CoV-2 supported by molecular dynamics simulation.

The novel strain of human coronavirus, emerged in December 2019, which has been designated as SARS-CoV-2, causes a severe acute respiratory syndrome. Since then, it has arisen as a serious threat to the world public health. Since no approved vaccines or drugs has been found to efficiently stop the virulent spread of the virus, progressive inquiries targeting these viruses are urgently needed, especially those from plant sources. Metabolic profiling using LC-HR-ESI-MS of the butanol extract of Ocimum menthiifolium (Lamiaceae) aerial parts yielded 10 compounds including flavonoids, iridoids and phenolics. As it has been previously reported that some flavonoids can be used as anti-SARS drugs by targeting SARS-CoV-1 3CLpro, we chose to examine 14 flavonoids (detected by metabolomics and other compounds isolated via several chromatographic techniques). We investigated their potential binding interactions with the 4 main SARS-CoV-2 targets: Mpro, nsp16/nsp10 complex, ACE2-PD and RBD-S-protein via molecular docking. Docking results indicated that the nsp16/nsp10 complex has the best binding affinities where the strongest binding was detected with apigenin-7-O-rutinoside, prunin and acaciin with -9.4, -9.3 and -9.3 kcal/mol binding energy, respectively, compared to the control (SAM) with -8.2 kcal/mol. Furthermore, the stability of these complexes was studied using molecular dynamics of 150 ns, which were then compared to their complexes in the other three targets. MM-PBSA calculations suggested the high stability of acaciin-nsp16 complex with binding energy of -110 kJ/mol. This study sheds light on the structure-based design of natural flavonoids as anti-SARS-CoV-2 drugs targeting the nsp16/10 complex.Communicated by Ramaswamy H. Sarma.

Cytotoxic and anti-diabetic potential, metabolic profiling and insilico studies of Syzygium cumini (L.) Skeels belonging to family Myrtaceae.

LC-HR-MS-coupled metabolic profiling of the methanol extracts from different parts of Syzygium cumini (L.), which was extensively identified via DNA fingerprinting, led to dereplication of 24 compounds. Cytotoxic investigation highlighted both extracts as the most potent, against both MCF-7 and MDA-231 Cell lines, with IC50 value of 5.86 ± 0.63 µg/ml and against HCT -116 cell line, with IC50 value of 1.24 ± 0.09 µg/ml, respectively. A molecular docking study was performed on the dereplicated compounds, which highlighted myricetin-3-glucoside (7), myricitrin (12), reynoutrin (15) and quercitrin (16) as the top scoring ligands within the protein active site (FIH-1). Interestingly, the extracts were significant against streptozotocin-induced diabetes in the order of flowers > seeds > leaves with BGL level of 98.9 ± 4.3, 123.2 ± 4.9 and 132.8 ± 5.9 mg/dl, respectively. The study highlights the health benefits of Syzygium cumini (L.) as a promising cytotoxic source.

Scabicidal Potential of Coconut Seed Extract in Rabbits via Downregulating Inflammatory/Immune Cross Talk: A Comprehensive Phytochemical/GC-MS and In Silico Proof.

Scabies is an invasive skin condition caused by Sarcoptes scabiei mites. The present study investigates the antiscabies potential of coconut seed extract (CSE) in rabbits. GC-MS analysis of the seed oil identified 17 known compounds, while CSE phytochemical investigation afforded 4 known ones. The topical application of seed extract improved all signs of infection, and the improvement started 3 days post application. However, in vitro application of the extract caused 99% mortality of mites 1 day post application. Histopathological examination revealed the absence of inflammatory infiltration and hyperkeratosis of the epidermis, compared with ivermectin-treated groups which revealed less improvement. The mRNA gene expression results revealed a suppression of IL-1ß, IL-6, IL-10, MMP-9, VEGF, and MCP-1, and an upregulation of I-CAM-1, KGF as well as TIMP-1. The docking analysis emphasized a strong binding of gondoic acid with IL-1ß, IL-6, and VEGF with high binding scores of -5.817, -5.291, and -8.362 kcal/mol, respectively, and a high binding affinity of 3″(1‴-O-ß-D-glucopyranosyl)-sucrose with GST with -7.24 kcal/mol. Accordingly, and for the first time, our results highlighted the scabicidal potential of coconut seed extract, which opens the gate for an efficient, cost-effective as well as herbal-based alternative for the control of scabies in rabbits.

Nannochloropsis oculata feed additive alleviates mercuric chloride-induced toxicity in Nile tilapia (Oreochromis niloticus).

Using microalgae to alleviate the adverse effects of aquaculture pollutants, including metals, has recently gained much attention. In this context, bioaccumulation, hematological indices, oxidative and antioxidant responses, and histopathological alterations were investigated in Nile tilapia (Oreochromis niloticus) fed with either a control diet or diets containing Nannochloropsis oculata (N. oculata) after exposure to mercuric chloride in order to evaluate the role of this microalgae in protecting against mercury-induced toxicity. Fish exposed to HgCl2 at a dose of » LC50 (0.3 mg/L) (Hg group) for 7-21 days exhibited a significant increase in total mercury concentration with a bioaccumulation pattern of liver>gills>muscle, and a significant decrease in all blood indices except mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), monocyte counts, and neutrophil counts. Malondialdehyde (MDA) levels were significantly increased in the Hg group at all time points relative to the control. Glutathione peroxidase (GPx) activity was significantly increased at days 14 and 21, while catalase (CAT) and GPx activities increased and decreased, respectively, at day 7 compared to the control. Additionally, lysozyme activity and immunoglobulin M (IgM) were significantly decreased in the Hg-exposed group. Severe histopathological alterations were evident in the liver, kidneys, and gills. However, supplementation with N. oculata at a low (5%, 50 g/kg feed) or high (10%, 100 g/kg feed) dose stabilized all parameters and reduced the severity of the histopathological alterations with the high N. oculata diet showing more prominent effects. These results suggest that feeding N. oculata protects Nile tilapia against mercuric chloride-induced toxicity.

Adverse effects of atrazine on blood parameters, biochemical profile and genotoxicity of snow trout (Schizothorax plagiostomus).

This study was conducted to evaluate the adverse effects of atrazine on hematology, biochemistry and genotoxicity of snow trout (Schizothorax plagiostomus). Almost all treated groups presented considerably (P < 0.05) lesser values of hematocrit, hemoglobin, WBC, RBC, MCH, MCHC, monocytes and lymphocytes while significantly higher values of HCT and platelets are observed. A Significant decrease is observed in sodium, calcium, potassium, phosphorous, triglycerides, creatinine, urea, and total protein contents whereas, a significant increase is observed in cholesterol and glucose level. Significant (P < 0.05) alterations are observed in enzyme activities of all treated groups. DNA damage was observed at the concentrations (2-4 ppm). Results showed that Comet assay is reliable for evaluating the toxicity and is helpful in environmental monitoring programs.

New Acaciin-Loaded Self-Assembled Nanofibers as MPro Inhibitors Against BCV as a Surrogate Model for SARS-CoV-2.

BACKGROUND: SARS-COVID-2 has recently been one of the most life-threatening problems which urgently needs new therapeutic antiviral agents, especially those of herbal origin. PURPOSE: The study aimed to load acaciin (ACA) into the new self-assembled nanofibers (NFs) followed by investigating their possible antiviral effect against bovine coronavirus (BCV) as a surrogate model for SARS-COV-2. METHODS: ACA was identified using 1H-NMR and DEPT-Q 13C-NMR spectroscopy, the molecular docking study was performed using Autodock 4 and a modification of the traditional solvent injection method was applied for the synthesis of the biodegradable NFs. Different characterization techniques were used to inspect the formation of the NFs, which is followed by antiviral investigation against BCV as well as MTT assay using MDBK cells. RESULTS: Core/shell NFs, ranging between 80-330 nm with tiny thorn-like branches, were formed which attained an enhanced encapsulation efficiency (97.5 ± 0.53%, P<0.05) and a dual controlled release (a burst release of 65% at 1 h and a sustained release up to >24 h). The antiviral investigation of the formed NFs revealed a significant inhibition of 98.88 ± 0.16% (P<0.05) with IC50 of 12.6 µM against BCV cells. CONCLUSION: The results introduced a new, time/cost-saving strategy for the synthesis of biodegradable NFs without the need for electric current or hazardous cross-linking agents. Moreover, it provided an innovative avenue for the discovery of drugs of herbal origin for the fight against SARS-CoV-2 infection.

A Glossary for Chemical Approaches towards Unlocking the Trove of Metabolic Treasures in Actinomycetes.

Actinobacterial natural products showed a critical basis for the discovery of new antibiotics as well as other lead secondary metabolites. Varied environmental and physiological signals touch the antibiotic machinery that faced a serious decline in the last decades. The reason was exposed by genomic sequencing data, which revealed that Actinomycetes harbor a large portion of silent biosynthetic gene clusters in their genomes that encrypt for secondary metabolites. These gene clusters are linked with a great reservoir of yet unknown molecules, and arranging them is considered a major challenge for biotechnology approaches. In the present paper, we discuss the recent strategies that have been taken to augment the yield of secondary metabolites via awakening these cryptic genes in Actinomycetes with emphasis on chemical signaling molecules used to induce the antibiotics biosynthesis. The rationale, types, applications and mechanisms are discussed in detail, to reveal the productive path for the unearthing of new metabolites, covering the literature until the end of 2020.