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This dissertation is divided into two main sections: the first focuses on retinal diseases and their associated in-vitro models, while the second explores advancements in cell therapies for treating retinal diseases. The eyes include the complex neurosensory system that facilitates our visual perception. The cells responsible for transmitting visual information from the eye to the brain include photosensitive rods and cones, interneurons, and ganglion cells, which operate in concert. This information is carried to the brain via the optic nerve bundle, located towards the back of the eye. The neural retina is situated above the pigmented monolayer, known as the retinal pigmented epithelium (RPE), which serves both as a protective barrier shielding the neural retina from adjacent blood vessels and as a support system. The RPE also provides nutrients and protection to maintain the health and functionality of nearby photoreceptors. Mutations affecting various cell types in the eye have been identified, and while our understanding of conditions such as Age-Related Macular Degeneration (AMD) and Retinitis Pigmentosa (RP) has significantly improved in recent years, some remain poorly understood. First, we will review the current landscape describing several inherited retinal dystrophies and relevant stem-cell-derived models (Chapter I). Second, we describe an in-vitro model of stem-cell derived RPE that recapitulates several features of Danon disease (DD), a multi systemic disease caused by 2mutations in Lysosome Associated Membrane Protein 2 (LAMP2) that can affect a patient’s vision. We provide mechanistic insights on how loss of LAMP2 can impair RPE function and longevity (Chapter II). To address the growing number of patients with retinal diseases, multiple research groups have utilized stem cell biology to generate cell banks of affected cell types. The goal is to replace degenerative tissue with healthy and viable cells, offering potential treatment options for patients. One such project targets AMD and includes replacing dysfunctional RPE with healthy ones. Several challenges have emergedincluding long-term storage, production and scalability. Here we describe methods to produce viable and functional RPE cells at scales necessary to treat the afflicted population of individuals suffering from AMD (Chapter III). Additionally, we address storage difficulties by detailing methods to cryopreserve clinical grade RPE implants that yield viable and functional cells post thaw (Chapter IV). The final section of this dissertation provides insights into additional work and future directions presented herein (Chapter V). We build upon previous studies describing retinal diseases associated with several dystrophies, understanding the pathogenicity of DD associated vision loss and develop methodologies to improve cellular therapies targeting AMD

Matters arising from: Mapping the human genetic architecture of COVID-19 Original Article published on 08 July 2021 https://www.nature.com/articles/s41586-021-03767-x The COVID-19 pandemic continues to pose a major public health threat, especially in countries with low vaccination rates. To better understand the biological underpinnings of SARS-CoV-2 infection and COVID-19 severity, we formed the COVID-19 Host Genetics Initiative1. Here we present a genome-wide association study meta-analysis of up to 125,584 cases and over 2.5 million control individuals across 60 studies from 25 countries, adding 11 genome-wide significant loci compared with those previously identified2. Genes at new loci, including SFTPD, MUC5B and ACE2, reveal compelling insights regarding disease susceptibility and severity. Here we present meta-analyses bringing together 60 studies from 25 countries (Fig. 1 and Supplementary Table 1) for three COVID-19-related phenotypes: (1) individuals critically ill with COVID-19 on the basis of requiring respiratory support in hospital or who died as a consequence of the disease (9,376 cases, of which 3,197 are new in this data release, and 1,776,645 control individuals); (2) individuals with moderate or severe COVID-19 defined as those hospitalized due to symptoms associated with the infection (25,027 cases, 11,386 new and 2,836,272 control individuals); and (3) all cases with reported SARS-CoV-2 infection regardless of symptoms (125,584 cases, 76,022 new and 2,575,347 control individuals). Most studies have reported results before the roll out of the COVID-19 vaccination campaign. An overview of the study design is provided in Supplementary Fig. 1. We found a total of 23 genome-wide significant loci (P

Background:Cannabis has been cultivated and used for centuries in the north Moroccan Rif (local name is kif). However, its history is poorly known and the date of its first introduction and dispersal in Morocco is still difficult to be precise. Aim: The purpose of the present work is to review the literature on the origin, history, and cultivation of Cannabis in Morocco, as well as data on the morphological, genetic, and phytochemical characteristics of local cultivated varieties. Discussion: Considering the importance of preserving the fragile environment of the Rif and the future development of the Moroccan medical Cannabis market, which will require authentication of the raw material, the use of local strains which are well adapted to the particular environment of the Rif is highly recommended. However, there is no document that summarizes and clarifies the nomenclature and the characteristics of local Moroccan Cannabis. In addition, the recent adoption by Rif growers of improved hybrid cultivars is obliterating the traits and peculiarities of Moroccan Cannabis through genetic introgression. Conclusion: Summarizing and discussing the data from the literature on the characteristics of local Moroccan Cannabis varieties may be useful for their identification and the localization of the areas of the Rif region where their cultivation is still practiced.

Apiaceae plants are multipurpose folk remedies and bioactive foods that show a remarkable ability to biosynthesize a large number of secondary metabolites with antitumor and chemopreventive potential. Among the various members of the Apiaceae, celery (Apium graveolens L.) has long been used as a popular edible and medicinal plant owing to its plentiful health benefits and nutraceutical properties; however, the anticancer potential of this important species has been seldom studied, mostly focusing on its seeds. Therefore, this work was designed to delve into the chemical composition and anti-proliferative potential of the total ethanolic extracts of the aerial parts (TEEAGA) and roots (TEEAGR) of A. graveolens var. dulce (Mill.) Pers. as well as their green synthesized silver nanoparticles (AgNPs). In general, both TEEAGA and TEEAGR exhibited moderate to potent inhibitory activities against human liver (HepG-2), colon (Caco-2), and breast (MCF-7) cancer cell lines, with interesting IC50 profiles [(41.37 ± 0.12, 27.65 ± 0.27, and 9.48 ± 0.04 μg/mL) and (11.58 ± 0.02, 7.13 ± 0.03, and 6.58 ± 0.02 μg/mL), respectively] as compared with doxorubicin, while more pronounced anti-proliferative effects were observed for their biogenic AgNPs, which showed IC50 values ranging between 25.41 ± 0.16 and 1.37 ± 0.03 μg/mL. Moreover, HPLC‒HESI‒HRMS-based metabolomics analysis of both extracts showed the presence of a varied group of secondary metabolites, including flavonoids, phenylpropanoids, phthalides, coumarins, and sesquiterpenes that further displayed moderate to promising binding affinities to the active site of cyclin G-associated kinase (GAK), particularly graveobioside A, graveobioside B, and celeroside C, suggesting their possible contribution as GAK modulators to the anti-proliferative potential of celery. These findings can help broaden future research on the utilization of different parts of celery and their NPs as functional foods and medicines in cancer chemoprevention and therapy.

Potato plants and their tubers in Egypt are affected by one of the most renowned soil-borne pathogen, Ralstonia solanacearum, that caused brown rot in potato tubers and wilt in plants. There is no efficient therapeutic bactericide so; control of bacterial wilt is very rough. The study investigated three different concentrations of seven essential plant oils under in vitro and in vivo conditions as a result of their effects on Ralstonia solanacearum growth and their possibility use as potato seed pieces dressing for controlling bacterial wilt disease incidence. In vitro, anise oil at the three tested different concentrations (0.04, 0.07, and 0.14% vol/vol) was the most effective one inhibiting the growth of T4 and W9 isolates of Ralstonia solanacearum then pursued by thyme, lemongrass, and clove oils. On the other hand, rocket oil at the tested concentration was the least effective one followed by fennel oil. However, wheat germ oil was not completely effective. In vivo, experiment revealed that anise oil at the three concentrations significantly reduced disease incidence and severity in sponta and hermes potato cultivars and their effect was associated with increase of peroxidase, polyphenoloxidase, phenols and the foliar fresh weight of treated plants as well as the weight of tubers/plant followed by thyme and lemongrass oils compared to the infected untreated control. Morphological differences in bacterial cell structure have been observed using a transmission electron microscope (TEM). Anise oil at higher concentration caused of cell wall rupture and degraded cellular components.

Bacterial wilt is one of the main diseases of Solanum spp., which caused by Ralstonia solanacearum (RS), formerly known as Pseudomonas solanacearum. Different concentrations of chitosan nanoparticles have been evaluated as one of the alternative methods of disease management in vitro and in vivo to reduce the risks of pesticide residues. Results in vitro experiment indicated that RS5 isolate was the most virulence one compared to RS1 and RS3. Increasing concentration of nano-chitosan, lead to increase inhibition zone, and this was observed at higher concentrations (100 and 200 µg/ml). In vivo results showed the highest concentration of spraying chitosan nanoparticles increase percentage reduction of disease incidence and severity, in effected potato and tomato plants. Recorded data of disease incidence and severity in treated potato plants were 78.93 % and 71.85 %, while on tomato plants were 81.64 % and 77.63 %, respectively compared to untreated infected potato plants were recorded 15.38 %, 20.87 %, and tomato plants were 20.98 % and 28.64 %. Results also revealed that 100 µg/ml of chitosan nanoparticles the lowest treatments used as soil amended curative treatments led to incease percentage reduction of disease incidence and severity, respectively on potato and tomato plants, but less than preventive treatment. The results registered that on potato plant were 54.93 % and 52.65 %, whilst recorded on tomato plants were 59.93 % and 56.74 %. Transmission electron microscopy (TEM) micrpgraphs illustrated that morphological of healthy R. solanacearum cells were undesirably stained with uranyl. The electron-dense uranyl acetate dye was limited to the cell surface slightly than the cytoplasm, which designated the integrity of the cell film of healthy cells. While bacterial cells treated with nano-chitosan, showed modification in the external shape, such as lysis of the cell wall and loss of cell flagella. Also, the result of using Random amplified polymorphic DNA (RAPD)-PCR observed that differences in treated Ralstonia solanancearum genotype by nano-chitosan compared to the genotype of the same untreated isolate.

Fungi are considered a prosperous pool of microbial bio-metabolites. Terretonins are meroterpenoids that are reported mainly from the Aspergillus genus. They exhibit unique tetracyclic core skeletons and various bioactivities. The current review summarizes the published researches on the source, biosynthesis, isolation, structural characterization, and bioactivities of terretonins that have been reported from Aspergillus species, as well as from synthetic sources. A literature search on the published studies was conducted over different databases, including Web of Science, MedLine (PubMed), Scopus, SpringerLink, Google Scholar, SciFinder, Wiley, and ACS Publications up to 2020. In this work, 18 compounds from Aspergillus species and synthetic sources are depicted. They have unrivaled and diversified skeletons as well as various bioactivities. Moreover, 37 references are included. Terretonins form a class of fungal bio-metabolites that attain all the characters for becoming lead compounds in their particular therapeutic category.

Drought stress adversely affects plant health and productivity. Recently, drought-resistant bacterial isolates are used to combat drought resistance in crops. In this in vitro study, 20 bacterial isolates were isolated from harsh soil; their drought tolerance was evaluated using four concentrations of polyethylene glycol (PEG) 6000. The two most efficient isolates (DS4 and DS9) were selected and identified using 16S rRNA genetic sequencing. They were registered in the NCBI database and deposited under accession numbers MW916285 and MW916307 for Bacillus cereus (DS4) and Bacillus albus (DS9), respectively. These isolates were screened for plant growth-promoting properties compared to non-stressed conditions. Biochemical parameters; Proline, salicylic acid, gibberellic acid (GA), indole acetic acid (IAA), antioxidant activity, and antioxidant enzymes were measured under the same conditions, and in vitro seed germination was tested under stress conditions and inoculation with selected isolates. The results showed that under the harsh conditions of PEG6000, DS4 produced the highest amount of IAA of 1.61 µg/ml, followed by DS9 with 0.9 µg/ml. The highest amount of GA (49.95 µg/ml) was produced by DS9. On the other hand, the highest amount of siderophore was produced from DS4 isolate followed by DS9. Additionally, DS4 isolate recorded the highest exopolysaccharide (EPS) content of 3.4 mg/ml under PEG (-1.2 MPa) followed by DS9. The antioxidant activity increased in PEG concentrations depending manner, and the activity of the antioxidant enzymes increased, as catalase (CAT) recorded the highest activity in DS4 with an amount of 1.095 mg/ml. additionally, an increase in biofilm formation was observed under drought conditions. The isolated mixture protected the plant from the harmful effects of drought and showed an increase in the measured variables. Under unstressed conditions, the highest rates of emulsification index (EI 24%) were obtained for DS4 and DS9, at 14.92 and 11.54, respectively, and decreased under stress. The highest values of germination, total seedling length, and vigor index were obtained upon inoculation with the combination of two strains, and were 100%, 4.10 cm, and 410, respectively. Therefore, two strains combination is an effective vaccine capable of developing and improving drought tolerance in dryland plants.

This study aimed to evaluate the efficacy of chitosan-silver nanocomposites in the treatment of experimentally infested pigeons with Pseudolynchia canariensis (P. canariensis) with evaluation of different immunological parameters before and after treatment. Therefore, fourteen birds were divided into 2 groups; group1(infested group including 12 birds) which subdivided into 6 sub-groups experimentally infested pigeons 2 pigeons each, and five group of them were treated with chitosan-silver nanocomposites and sub-group number 6 was treated with deltamethrin while, group 2 including two pigeons were kept as control negative ones. P. canariensis flies distributed under the wing and /or under the tail in infested group and these pigeons showed significantly lower RBCs and higher WBCs than that in non-infested pigeons. The cell mediated immune response against experimentally infested pigeons with P. canariensis was studied. P. canariensis infestation in pigeons have a negative impact on pigeon’s blood parameters, increase TNF-α and IL-1β cytokines levels. This study cleared out the role of P. canariensis in the induction of a case of oxidative stress indicated by high level of nitric oxide and malondialdehyde (MDA) with low antioxidant capacity in shape of reduced zinc concentration in the sera of experimentally infested pigeon. Chitosan-silver nanocomposite has a promising effect in the elimination of P. canariensis infestation in pigeons.

Water stress is a critical abiotic stress for plant reduction in arid and semiarid zones and, has been discovered to be detrimental to the development of seedlings as well as the growth and physiological characteristics of many crops such as cotton. The objectives of our study were to determine the combining ability and genetic components for five quantitative traits [(leaf area (LA), leaf dry weight (LDW), plant height (PH), fiber length (2.5 percent SL), and lint cotton yield/plant (LCY/P)] under water shortage stress, a half diallel cross between six cotton genotypes representing a wide range of cotton characteristics was evaluated in RCBD with four replications. The genotype mean squares were significant for all traits studied, demonstrating significant variation among genotypes for all characters under water shortage stress. LCY/P had the highest phenotypic and genotypic correlation co-efficient with PH, LDW, and LA shortage. The highest direct effect on lint cotton yield was exhibited by leaf area (3.905), and the highest indirect effects of all traits were through LA, with the exception of 2.5 percent SL, which was through LDW. The highest dissimilarity (Euclidean Distance) between parental genotypes was between G.87 and G.94, followed by G.87 and Menoufi. G.94 was also a well-adapted genotype, and the combinations G.87 x G.94 and G.87 x Menoufi may outperform their parents. The combining ability analysis revealed highly significant differences between parental GCA effects and F1 crosses SCA effects. The variation of GCA and SCA demonstrated the assurance of additive and non- additive gene action in the inheritance of all traits studied. In terms of general combining ability (GCA) effects, parental genotype G.94 demonstrated the highest significant and positive GCA effects for all traits studied, with the exception of 2.5 percent SL, where G.87 revealed the highest significant and positive GCA effects. The effects of specific combining ability (SCA) revealed that the cross (G.87 x2G.94) revealed stable, positive, and significant SCA for all of the studied traits.

The enhanced understanding of chloroplast genomics would facilitate various biotechnology applications; however, the chloroplast (cp) genome / plastome characteristics of plants like Fagonia indica Burm.f. (family Zygophyllaceae), which have the capability to grow in extremely hot sand desert, have been rarely understood. The de novo genome sequence of F. indica using the Illumina high-throughput sequencing technology determined 128,379 bp long cp genome, encode 115 unique coding genes. The present study added the evidence of the loss of a copy of the IR in the cp genome of the taxa capable to grow in the hot sand desert. The maximum likelihood analysis revealed two distinct sub-clades i.e. Krameriaceae and Zygophyllaceae of the order Zygophyllales, nested within fabids.

Microglia are the resident immune cells of the brain and play a crucial role in housekeeping and maintaining homeostasis of the brain microenvironment. Upon injury or disease, microglial cells become activated, at least partly, via signals initiated by injured neurons. Activated microglia, thereby, contribute to both neuroprotection and neuroinflammation. However, sustained microglial activation initiates a chronic neuroinflammatory response which can disturb neuronal health and disrupt communications between neurons and microglia. Thus, microglia-neuron crosstalk is critical in a healthy brain as well as during states of injury or disease. As most studies focus on how neurons and microglia act in isolation during neurotrauma, there is a need to understand the interplay between these cells in brain pathophysiology. This review highlights how neurons and microglia reciprocally communicate under physiological conditions and during brain injury and disease. Furthermore, the modes of microglia-neuron communication are exposed, focusing on cell-contact dependent signaling and communication by the secretion of soluble factors like cytokines and growth factors. In addition, how microglia-neuron interactions could exert either beneficial neurotrophic effects or pathologic proinflammatory responses are discussed. We further explore how aberrations in microglia-neuron crosstalk may be involved in central nervous system (CNS) anomalies, namely: traumatic brain injury (TBI), neurodegeneration, and ischemic stroke. A clear understanding of how the microglia-neuron crosstalk contributes to the pathogenesis of brain pathologies may offer novel therapeutic avenues of brain trauma treatment.

Great attention has been given to plants in the context of their growth, nutritional value and biological activity. The present work is designed to use the bioactive Punica granatum L. Peel (PoPe) extracts as an eco-friendly approach to improve Brassica oleraceae (B. oleraceae) growth and nutritive values. The phytochemical profile, in vitro antibacterial potential and in vitro antioxidant DPPH free radical activity of aqueous (Aq) and ethanol (EtOH) extracts of PoPe were investigated to select the potent PoPe extract. A strong antibacterial activity of both extracts and EtOH extract of PoPe had the highest DPPH activity. According to GC/MS analysis, high content of phenolic components in EtOH extract of PoPe with the highest concentration of Eugenol (58.95%). Thus, seeds of three B. oleraceae varieties i.e., acephala (BA1), acephala (BA2) and italic (BA3) were primed with EtOH extract of PoPe to test their impacts on growth, glucosinolate metabolism, and biological activities. EtOH extract of PoPe induced glucosinolate accumulation in all the three varieties BA1, BA2, and BA2, possibly through amino acids production. Interestingly, a reduced level of effective sulforaphane nitrile was measured and positively correlated with decreased epithiospecifier protein. Consequently, there was an increase in the antioxidant DPPH of BA1 and BA2 (84% and 183%, respectively) and increase in FRAP of BA1 (117%). Further, the antibacterial activities of PoPe treated varieties were increased, however, a decrease was observed in PoPe treated BA1 and BA2 against Pseudomonas aeruginosa and BA2 against Klebsiella pneumonia. In conclusion, PoPe extract is a rich source of metabolites that could enrich B. oleraceae sprouts with health-promoting metabolites and bioactivities.

Fifty broiler chicks were divided into five groups to study the antiviral and immune-stimulant effect of Allium cepa essential oils (ACEO). The effect of Allium cepa essential oils administration single or combined with NVD vaccine in broilers, more than one parameter was studied in this study i.e., the clinical symptoms that appeared on the chicks after the experimental infection with velogenic Newcastle disease virus, postmortem lesions, pathological lesions scoring, mortality rate (MR), and viral shedding, birds immunity was assessed by HI test and protection percent post-challenge with vNDV. Our result showed that mild clinical signs, lesion scoring, decreased viral shedding in ACEO treated groups 3 (G 3) more than control groups post-challenge with vNDV. Delayed onset of mild clinical signs in G3 followed by complete recovery 7th-day post-challenge (DPC). Low MR (40 and 0%) and high protection percent (100 and 60%) in ACEO treated G3 and G5, respectively. spleen, thymus, cecal tonsil, proventriculus, and cerebrum lesions scoring in G3 and G5 were significantly ((p ≤ 0.05).) lower than the control group, proving a decrease in NDV replication and effective antiviral activity of ACEO. HI titer significantly increased (p ≤ 0.05) In G3, G4 and G5 compared with control groups. There is no significant difference in HI titer in ACEO treated groups and vaccinated groups. In conclusion, oral administration of ACEO combined with NDV vaccines significantly reduces or eliminates lethal clinical signs, lesions, viral shedding, and enhances immune response and protection percent after vNDV challenge proving the natural antiviral and immune stimulant effect of ACEO onion extract. Implementing such a regime might aid NDV control in broiler flocks in endemic areas and reduce the epidemiological load of NDV in the environment.

Introduction Although the molecular profile of the breast provides prognostic indicators, risk stratification in breast cancer continues to be a challenge. Therefore, it is mandatory to seek new prognostic markers that could aid the early diagnosis of potential metastases in biopsy samples from breast cancer; among these are increased Snail-1 and Claudin-4 expression. Objectives The aim of this study was to analyze the correlation between Snail-1 and Claudin-4 with other clinical-pathological parameters and distinct molecular subtypes. Methods This study included 110 patients with invasive ductal carcinoma from 2009 to January 2015. Snail-1 and Claudin-4 were assessed by immunohistochemistry in formalin-fixed paraffin-embedded tissue blocks and the data were correlated with clinical-pathological data and survival. Results A total of 65 patients (68.2%) were positive for Snail-1 and 85 patients (77.3%) were positive for Claudin-4. High Snail-1 and high Claudin-4 were detected in high-grade tumors and were associated with lymphovascular infiltration and lymph node metastases (p Conclusion High Snail-1 and Claudin-4 levels were associated with adverse outcomes in patients with breast cancer.

This study investigates the inhibitory effects of thalli and their extracts of the macroalga Turbinaria ornata on the germination of dinoflagellate cysts, previously isolated from Red Sea surface sediments. The experiments were conducted on cysts of five harmful dinoflagellate species including Alexandrium catenella, Cochlodinium polykrikos, Dinophysis accuminata, Prorocentrum cordatum and Scrippsiella trochoidea. The results showed neither macroalgal thalli nor their extracts had direct impact on the cyst germination of all species. Instead, these macroalgal materials remarkably affected the germling viability and culturability of progeny cells of these cysts. Dry macroalgal thalli exhibited stronger inhibitory effects on germling viability and cell culturability (IC50= 0.235-–0.543, 0.385–1.43 mg mL−1, respectively) than fresh thalli (IC50=2.201-–4.716, 2.17–7.18 mg mL−1, respectively). The macroalgal ethanol extract was approximately 2-5 times more effective (IC50 = 0.012–0.047 and 0.024–0.089 mg mL−1, respectively) than aqueous extract (IC50 = 0.04–0.1 and 0.054–0.207 mg mL−1, respectively) against the germling viability and vegetative progeny cells of all cyst species. Among different species, A. catenella and C. polykrikos germlings were more sensitive to macroalgal thalli and their extracts than those of S. trochoidea, P. cordatum and D. acuminata. Meanwhile, progeny cells of A. catenella exhibited the highest sensitivity to all macroalgal materials. Our results suggest that the use of T. ornata may be a promising strategy for inhibiting the division of progeny cells of dinoflagellate cysts and impairing the recurrence of HABs in confined coastal areas.

Bacillus Calmette–Guérin (BCG) vaccine is currently used to prevent tuberculosis infection. The vaccine was found to enhance resistance to certain types of infection including positive sense RNA viruses. The current COVID-19 pandemic is caused by positive sense RNA, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A higher mortality rate of COVID-19 patients was reported in countries where BCG vaccination is not routinely administered, when compared to the vaccinated ones. We hypothesized that BCG vaccine may control SARS-CoV2 infection via modulating the monocyte immune response. We analyzed GSE104149 dataset to investigate whether human monocytes of BCG-vaccinated individuals acquire resistance to SARS-CoV-2 infection. Differentially expressed genes obtained from the dataset were used to determine enriched pathways, biological processes, and molecular functions for monocytes post BCG vaccination. Our data show that BCG vaccine promotes a more effective immune response of monocytes against SARS-CoV2, but probably not sufficient to prevent the infection.

The infectious bronchitis virus (IBV) 4/91 was one of the common IBV variants isolated in Eastern Canada between 2013 and 2017 from chicken flocks showing severe respiratory and production problems. We designed an in vivo experiment, using specific pathogen free (SPF) chickens, to study the pathogenesis of, and host response to, Canadian (CAN) 4/91 IBV infection. At one week of age, the chickens were infected with 4/91 IBV/Ck/Can/17-038913 isolate. Swab samples were collected at predetermined time points. Five birds from the infected and the control groups were euthanized at 3, 7- and 10-days post-infection (dpi) to collect lung and kidney tissues. The results indicate IBV replication in these tissues at all three time points with prominent histological lesions, significant immune cell recruitment and up regulation of proinflammatory mediators. Overall, our findings add to the understanding of the pathogenesis of 4/91 infection and the subsequent host responses in the lungs and kidneys following experimental infection.

Background Accurate and repeatable measurement of high-grade glioma (HGG) enhancing (Enh.) and T2/FLAIR hyperintensity/edema (Ed.) is required for monitoring treatment response. 3D measurements can be used to inform the modified Response Assessment in Neuro-oncology criteria. We aim to develop an HGG volumetric measurement and visualization AI algorithm that is generalizable and repeatable. Methods A single 3D-Convoluted Neural Network, NS-HGlio, to analyze HGG on MRIs using 5-fold cross validation was developed using retrospective (557 MRIs), multicentre (38 sites) and multivendor (32 scanners) dataset divided into training (70%), validation (20%), and testing (10%). Six neuroradiologists created the ground truth (GT). Additional Internal validation (IV, three institutions) using 70 MRIs, and External validation (EV, single institution) using 40 MRIs through measuring the Dice Similarity Coefficient (DSC) of Enh., Ed. ,and Enh. + Ed. (WholeLesion/WL) tumor tissue and repeatability testing on 14 subjects from the TCIA MGH-QIN-GBM dataset using volume correlations between timepoints were performed. Results IV Preoperative median DSC Enh. 0.89 (SD 0.11), Ed. 0.88 (0.28), WL 0.88 (0.11). EV Preoperative median DSC Enh. 0.82 (0.09), Ed. 0.83 (0.11), WL 0.86 (0.06). IV Postoperative median DSC Enh. 0.77 (SD 0.20), Ed 0.78. (SD 0.09), WL 0.78 (SD 0.11). EV Postoperative median DSC Enh. 0.75 (0.21), Ed 0.74 (0.12), WL 0.79 (0.07). Repeatability testing; Intraclass Correlation Coefficient of 0.95 Enh. and 0.92 Ed. Conclusion NS-HGlio is accurate, repeatable, and generalizable. The output can be used for visualization, documentation, treatment response monitoring, radiation planning, intra-operative targeting, and estimation of Residual Tumor Volume among others.

Background: Plants are a main source of drugs for the therapy of a large number of diseases. Objective: The aim of the present work is to evaluate the in vitro antioxidant and anti-α-amylase and anti-peroxidases (HPR) potentials of phenolic extracts obtained from three spontaneous plants; growing in the South of Algeria such as (Chamomilla pubescens, Pulicaria crispa, and Rhanterium adpressum). This is the first report on the study of α-amylase and horseradish peroxidase (HRP) inhibitory activity for phenolic extracts from the Chamomilla pubescens and Pulicaria crispa plants. Method: The antioxidant activity was evaluated in vitro using four tests: DPPH, CUPRAC, FRAP, and ABTS. The phenolic, flavonoid, and tannin compounds of the three selected Algerian plants were quantified. Also, the inhibition of α-amylase and HRP was evaluated. Results: The quantification of the total phenolic contents revealed that they are widely variable, and depending on extraction solvents, the highest content was recorded by the ethyl acetate extract of Chamomilla pubescens (flowers) 774.93±60.14mg/100 g of dry matter. In all the antioxidant tests, ethyl acetate extracts showed the most effective activity, which the best was (VCEAC = 65.62 ±0.50 µM/g dry matter) of Pulicaria crispa for the DPPH test. Furthermore, the results of α-amylase and peroxidase inhibitory effects indicated that all plants extracts have inhibitory effects on the two enzymes, with AEIC values ranged from 76.55±3.54 to 149.54±6.68 μM/g of dry matter for the α-amylase, and CEIC values ranged from 8.89±2.22 to 9668.31±254.42 μM/g of dry matter for the peroxidase (HRP). Conclusion: The present study results suggest that the three Algerian spontaneous plant species (Rhanterium adpressum, Pulicaria crispa, and Chamomilla pubescens) inhibit peroxidase and α-amylase and exhibit a high antioxidant activity what can be related to the treatment of diabetes and thyroid diseases.

The present work was carried out to study the effect of low caloric diet supplemented with fennel seeds or black cumin seeds and their mixture on obese adult females. The control group (G1) used low caloric diet with 1000 kcal without supplementation, while groups (2 and 3) used low caloric diet supplemented with 5 g black cumin and 5g fennel seeds seeds, respectively. On the other hand, group (4) used low caloric diet supplemented a mixture of 2.5 g fennel seeds and 2.5g black cumin seeds. All supplementation were mixed with a cup of light yoghurt in dinner meal. The study was performed for 4 weeks. Anthropometric measurements and levels of serum triglyceride, cholesterol, LDL and HDL were taken pre and post the study. Females taken low caloric diet supplemented with black cumin (G2) or mixture of black cumin and fennel (G4) recorded significant decrease in their BMI when compared to the control group. Cases supplemented with Fennel (G3) recorded insignificant decrease in their BMI. The total cholesterol decreased significantly in groups (2 and 4), while it was decreased insignificantly in group (3) compared to the control group. HDL levels increased significantly in groups (2 & 4) compared to group (1). Results of the present study indicated that significant decrease were in total body weight, BMI, WC, AC, TSF and AMC in group (2) which received black cumin seeds, followed by group (4) which received mixture of black cumin seeds and fennel seeds, followed by group (3) which received fennel seeds compared to the control group.

Alzheimer’s disease (AD) is a chronic neurodegenerative disease that usually starts slowly and worsens over time. Indeed, cognitive dysfunction, neuronal atrophy, and synaptic loss are associated with both AD and chronic stress. Ivermectin is commonly used in the treatment of different kinds of infections and infestations. So, this study aimed to evaluating the therapeutic effect of ivermectin at two different doses against oxidative stress induced Alzheimer disease in rats by aluminum chloride. Fifty rats were divided into 10 normal control (NC), 20 Alzheimer, and 20 Ivermectin (Iv) therapeutic groups. The antioxidant enzymes, superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities were assayed, and the oxidative stress marker, carbonyl protein was also determined in brain tissues. The results showed a significant reduction in activities of SOD and GPx, in addition to significant elevation in carbonyl protein level compared to NC group. While, administration of Iv to AD rats can improve the tested parameters compared to AD group. These results may indicate that Ivermectin can be used as a therapeutic candidate in Alzheimer disease which will need more studies to support that.

Cakile maritima ssp. aegyptiaca (Wild.) Nyman is growing with dimorphic leaf forms (entire or pinnatifid lamina) along the Mediterranean coast of Egypt. The cytotoxic activities of dried shoot systems of the two morphological forms were evaluated by testing and comparing the effects of ethanolic and aqueous extracts on the viability of five human cell lines. GC-MS analysis was performed to identify the bioactive and anticancer compounds present in the most active extracts. MTT assay indicated that both aqueous and ethanolic extracts have selective cytotoxic activities against cancer cell lines with no inhibitory activities against normal Wi38 or Vero cell lines. The underlying mechanism of cytotoxicity involved the induction of G2/M phase arrest in targeted cells MCF-7 and HCT-116 associated with inducing apoptosis in both cell lines, as indicated by Annexin-V assay. Apoptosis investigation in MCF-7 and HCT-116 cells treated with ethanolic extracts, was further investigated through RT-PCR, which exhibited elevation of proapoptotic genes of P53, BAX, Capase-3,6,7,8,9, and downregulation of antiapoptotic gene (BCL-2) upon treatment. The GC-MS analysis of ethanolic extracts of pinnatifid and entire forms revealed the existence of 18 and 13 compounds, respectively, with eleven compounds that were detected in pinnatifid form only and seven compounds were identified exclusively in the entire form. Molecular Docking study revealed that the identified compounds exhibited good binding affinity towards BCL-2 inhibition, and this agreed with the suggested apoptotic mechanism. To the best of authors' knowledge, this is the first scientific evidence underline the variability in the chemical composition associated with variable anticancer activities of dimorphic forms of C. maritima.Communicated by Ramaswamy H. Sarma.

Coronavirus disease 2019 (COVID-19) is a rapidly growing pandemic that requires urgent therapeutic intervention. Finding potential anti COVID-19 drugs aside from approved vaccines is progressively going on. The chemically diverse natural products represent valuable sources for drug leads. In this study, we aimed to find out safe and effective COVID-19 protease inhibitors from a library of natural products which share the main nucleus/skeleton of FDA-approved drugs that were employed in COVID-19 treatment guidelines or repurposed by previous studies. Our library was subjected to virtual screening against SARS-CoV Main protease (Mpro) using Molecular Operating Environment (MOE) software. Twenty-two out of those natural candidates showed higher binding scores compared to their analogues. We repurpose these natural products including alkaloids, glucosinolates, and phenolics as potential platforms for the development of anti-SARS-CoV-2 therapeutics. This study paves the way towards discovering a lead used in the treatment of COVID-19 from natural sources and introduces phytomedicines with dual therapeutic effects against COVID-19 besides their original pharmacological effects. We recommend further in vitro evaluation of their anti-COVID-19 activity and future clinical studies. Supplementary Information The online version contains supplementary material available at 10.1007/s11356-021-17642-9.

Trichoderma harzianum S7113 as an efficient fungal isolate for laccase production was identified using the 18S rRNA sequencing. T. harzianum S7113 attained its maximal laccase production level on the 14th day of static incubation at 28 °C and pH 5.0 using the inoculum size of 5 discs (14 mm), according to the one factor per time (OFT) method. The most appropriate carbon, organic and inorganic nitrogen sources to promote maximal laccase synthesis were glucose (15 g/L), beef extract (5 g/L), and ammonium chloride (4 g/L), respectively. Results of Response Surface Methodology (RSM) revealed that glucose, meat extract, and ammonium chloride concentrations of 17.54, 7.17, and 4.36 g/L respectively, at a pH value of 6.74 are the favorite conditions for high titer production. The ANOVA analysis highlighted an excellent match between the actual experimental results and the model predicted laccase production levels. The biodegradation of hydroquinone (HQ) by T. harzianum S7113 laccase was most efficient in the pH range of 5.0 to 6.5. The increase in laccase concentration led to a significant increase in the HQ conversion to get a biodegradation rate of 92 ± 2.6% with a laccase concentration of 0.75 U/mL after 3 h of reaction.

This experimental study was done at the Biological Control Laboratory, Sakha Agricultural Research Station, Sakha, Kafrelsheikh, Egypt. We aimed to estimate the impact of different cold (10 °C) storage durations [0 (non-cold-stored parasitized eggs), 3, 6, 9, 12, 15, 18, 21, 24, 27, and 30 days], on Trichogramma evanescens (Westwood) (Hymenoptera: Trichogrammatidae) during the pupal stage using the eggs of Sitotroga cerealella after exposing to T. evanescens. The emergence percentage of non-cold-stored eggs of S. cerealella was higher than all cold-stored durations. Also, the female’s percentages of T. evanescens in the cold storage durations were lower than the non-cold storage one, and they were influenced by extended cold storage durations. There were non-significant differences in the female’s longevity of T. evanescens obtained from 0, 3, and 6 days cold-stored parasitized eggs of S. cerealella at 10 °C, but it began to decrease from those produced after 9 days of cold-stored eggs. In addition, the emergence percentage in F1 progeny of T. evanescens was greater than 50% until 21 days of cold storage. It could be concluded that cold storage reduced the % emergence, % females, female’s longevity, and emergence percentage in F1 progeny of T. evanescens. For a successful biological control program, the decrease of T. evanescens performance after cold storage durations should be considered in mass production, and the release percentage should be increased by the equivalent of a lack of % emergence. Also, the economic importance of using cold storage periods in commercial mass rearing should be assessed in the biological control program.

Saudi journal of biological sciences 28(12), 7241-7247 (2021). doi:10.1016/j.sjbs.2021.08.023, Published by Elsevier, Amsterdam [u.a.]

Background Trachyspermum ammi (commonly known as Ajwain), a medicinal plant of the Apiaceae family is scientifically acknowledged to harbor potential bioactive compounds for the treatment of gastrointestinal issues, loss of appetite, bronchial difficulties, cough, inflammation, diarrhoea, headache, hypertension, stomach discomfort, bronchitis and influenza. Candida albicans is generally a commensal fungus found in the gastrointestinal and genitourinary systems. Objective This study was focused on secondary metabolites of T. ammi and its effects towards candidiasis infection as caused by C. albicans. Methods Phytochemical components of T. ammi as a crude extract were extracted through maceration method using three polar (ethanol, methanol and water) and two non-polar (chloroform and diethyl ether) solvents and subjected to 14 phytochemical tests. Further, the crude extract of T. ammi was analyzed over gas chromatography–mass spectroscopy (GC–MS) and Fourier transform infrared spectroscopy (FTIR). Evaluation of antimicrobial property of the extract was carried out by minimum fungal concentration (MFC) and minimal inhibitory concentration (MIC). In addition, cell reduction assay was performed using flowcytometry to confirm the antifungal effect of Ajwain crude extract. Results The aqueous extract showed high presence of phytochemicals including alkaloids, carbohydrates, flavonoids, resins, steroids, tannins, inorganic acids, organic acids, phenolic compounds, amino acids, protein and coumarins. GCM S analysis revealed seven bioactive compounds, in which thymol was detected in significant amount in the chromatogram. FTIR performance showed the presence of various stretching vibration including O H, C H, C C, C O, C N and C O C. However, the MFC and MIC of Ajwain extracts using different solvent showed that the methanolic extract possesses maximum antifungal efficacy at 250 μg/ml and 15.6 μg/ml, respectively. In addition, cell reduction assay exhibited significant cell reduction in Ajwain methanolic extract compared to the other crude extracts used in the study. Conclusion Overall, the findings revealed that Ajwain methanolic crude extract has antifungal activity against C. albicans; however, that further needs to be established at molecular level.

Cactus pear is a dominant crop to arid lands with high nutritional value. Its fruits are used in food processing as add value to food products. The current study planted cactus pear under three irrigation regimes (T1, T2, and T3) where two of them (T2 and T3) implicated severe deficit irrigation conditions on the crop. The relationship between applied irrigation water regimes and fruit physical and chemical properties including antioxidants, pigment and vitamin C content was studied. The study also aimed to utilize cactus pear’s pulp (CPP), as additive value, in the processing of wheat flour cupcake. Samples of cupcake were made by adding 20%, 40%, 60% and 80% CPP based on wheat flour weight. Fruits obtained under T2 and T3 treatments had higher color concentration than T1. T2 irrigation regime yielded higher content of total phenolic and flavonoid content (TPC and TFC) than those produced under T3 and T1. Antioxidant activity was the highest in T2. Thus, fruit pulp obtained from T2 was selected for cupcake making. The content of soluble solids was ⁓18 Brix in all treatments. VitC. was significantly higher (P≤0.05) in T3 (56.04 g AA/kg) than T1 (55.42 g AA/kg) and T2 (51.01 AA/kg). The content of betacyanins in T1 was higher (0.47 mg100mg dry weight) in fruits pulp than T2 and T3 (0.44 and 0.54 mg100mg dry weight). Sensory evaluation showed that fortification with 60% cactus pear pulp had the best sensory characteristics meanwhile cupcakes fortified with 80% cactus pear pulp was not acceptable.

Asthma is a chronic disease with abnormal inflammatory and immunological responses. The disease initiates by antigens in subjects with genetic susceptibility. However, environmental factors play a role in the initiation and exacerbation of asthma attack. Asthma is a T-helper 2 (Th2)-cell-mediated disease. Recent studies indicate that asthma is not a single disease entity, but it occurs with multiple phenotypes and endotypes. The pathophysiological changes in asthma include a series of continuous vicious circles of cellular activation contributing to the induction of chemokines and cytokines that potentiate inflammation. The heterogeneity of asthma influences the treatment response. The asthma pathogenesis is driven by varied sets of cells, such as eosinophils, basophils, neutrophils, macrophages, epithelial cells, and T cells. Macrophages induce a set of mediators that are involved in asthma pathogenesis and include MIF, Prostaglandin, CXCR3L, IL-12, IL-1ß, TSLP, IL-18, IL-33, LTC4, MMP-2, TNF-α, IL-17, IL-10, TGF-ß and IL-27. While, T-cells mediators effect in asthma is induced via TNF-α, IL-17, IL-10, TGF-ß, IL-27, Tim, GM-CSF, IL-2, IL-4, IL-13, INF- γ, and PPAR γ. However, the epithelial cells induced mediators potentiate proinflammatory effects, increase the number of Th2 cells, activate dendritic cells, increase the number of mast cells, and recruit eosinophils, basophils, neutrophils, T-cells, monocytes and dendritic cells. In this review, the role of T cells, macrophages, and epithelial cells is discussed.