Faculty of Biotechnology Research Paper
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Item Narrow band ultraviolet B therapy deactivates Th1/Th17 pathway and activates Th2 cytokines secretion in Egyptian psoriatic arthritis patients(TAYLOR & FRANCIS LTD, 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND, 01/01/2020) Farid, A; Tawfik, A; Elsioufy, B; Safwat, GPsoriasis is a chronic autoimmune disorder that affects 3-4% of the world population. Keratinocytes and immune cells in patient's skin secrets excess pro-inflammatory cytokines that in turn activates the differentiation of T helper cells (Th) into Th1 and Th17 and deactivates Th2 pathway. Several phototherapies have been used in treatment of moderate and severe psoriatic patients; among them narrowband ultraviolet B (NB-UVB, 311 nm) is the most effective. We aims to evaluate the therapeutic effect of NB-UVB exposure in 80 Egyptian plaque psoriatic patients with and without psoriasis arthritis development. This will be accomplished by measuring serum cytokines levels (IL-10, -12, -17, -23 and -34) and high sensitive C reactive protein before and after treatment. A significant elevation in Th2 pathway cytokine, IL-10, and significant decrease in Th1/Th17 pathway cytokines were observed after treatment. This indicates the success of NB-UVB therapy in down modulating IL-12 and IL-23/Th17 axis. The pathological conditions in psoriatic arthritis patients were improved by NB-UVB targeted to the skin. As serum cytokines levels in these patients indicated that the reduction in Th1/Th17 inflammatory cytokines and elevation of Th2 anti-inflammatory cytokines was not restricted to skin lesions only, but also, spread in patients' body and improve their pathologicItem Bioprospecting of Thermophilic Fungal Enzymes and Potential Applications(Springer, 01/01/2022) Balbool, Bassem A; Abo Nouh, Fatma Ahmed; Atef Gezaf, Sara; Mohamed, Akram H; Abdel-Azeemo, Ahmed MEnzymes are the catalysts of chemical reactions; they are responsible for many biotechnological applications and industries. Fungi are considered as a reservoir for various chemical compounds, which are involved in many industrial, pharmaceutical, agricultural, and medical applications. Fungi are considered from the few eukaryotic organisms that can grow over a high-temperature range and they could be classified into thermophilic and thermotolerant taxa. Fungal species showed the ability to produce several thermotolerant enzymes such as xylanase, laccase, proteases, and phytases. All fungal thermotolerant enzymes have been involved in industrial applications such as textile production, bakery production, fermentation processes, and other pharmaceutical applications. The current chapter will focus on the biodiversity of thermophilic fungi and the various applications it is involved in.Item Epithelial-Mesenchymal Transition Markers in HCVAssociated Hepatocellular Carcinoma: A Multivariate Follow Up Study(01/06/2022) Helal, Thanaa Elsayed; Aref, Ahmed; Gomaa, Asmaa Ibrahim; Nada, Ola; Abd-Elghaffar, Mohamed; Farouk, Khaled; Ehsan, Nermine AhmedObjective: Validated markers to predict recurrence after surgical resection of hepatocellular carcinoma (HCC) are needed. Little data is available regarding epithelial-mesenchymal transition (EMT) markers in HCC. The objective of this study was to investigate the expression of EMT markers and their correlation with clinicopathological variables and survival in hepatitis C virus (HCV)-associated HCC. Methods: This longitudinal study included 109 cases of HCV-associated HCC treated with surgical resection. Nine different EMT markers (vimentin, E-cadherin, N-cadherin, Stat3, Snail1, Slug, Twist1, Zeb1 and integrin α5) were evaluated on liver tissue from HCC cases. Twenty fresh HCC samples from the studied cases were used for gene expression of EMT markers by quantitative real time polymerase chain reaction (PCR). Results: EMT markers expression was 71%, 25%, 26%, 27%, 9%, 4%, 72%, 47%, 87% for vimentin, E-cadherin, N-cadherin, Stat3 snail1, slug, twist1, Zeb1 and integrin α5 respectively. EMT mRNA in HCC tissues correlated with protein expression by 50-70%. Vimentin was independent predictor of large tumor size (P=0.001), high risk of recurrence (HRR) (P=0.006) and shorter disease free survival (P=0.03) in multivariate analysis. Reduced E-cadherin was a predictor of HRR (P=0.002). Conclusion: Vimentin and E-cadherin were the most powerful prognostic EMT markers in HCV-associated HCC in prediction of recurrence.Item Evaluation of antiobesity and hepatorenal protective activities of Salvia ofcinalis extracts pre‑treatment in high‑fat diet‑induced obese rats(Springer Science, 01/06/2022) Othman, Mohamed S; Khaled, Azza M; Aleid, Ghada M; Fareid, Mohamed A; Hameed, Reda A; Abdelfattah, Mohamed S; Ezz Aldin, Doaa ; Abdel Moneim, Ahmed EThe present study evaluated the efects of Hail Salvia ofcinalis total extract (SOTE) and its high favonoid fraction (SOHFF) on the high-fat diet (HFD)-induced obesity and hepatorenal damage in rats. Salvia ofcinalis plants were collected from Hail region, Saudi Arabia. Rats were fed HFD and supplemented orally with SOTE (250 mg kg−1) or SOHFF (100 mg kg−1) or simvastatin (SVS; 10 mg kg−1) every day for 8 weeks. Compared to the controls, HFD-induced obesity led to signifcant increases in body weight, body weight gained, blood insulin, leptin, cardiac enzymes (LDH and CPK) activity, and athero- genic index (AI). HFD rats also showed higher levels of hepatic and renal function biomarkers (ALT, urea, and creatinine), as well as lower levels of PPARγ and Nrf2-gene expression and a disrupted lipid profle. Moreover, HFD rats had lower levels of hepatic and renal antioxidant biomarkers (CAT, GPx, SOD, GR, and GSH), accompanied by higher levels of hepatic and renal lipid peroxidation (LPO), nitric oxide (NO), and infammatory mediators (interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α)). In addition, histological examination of hepatic and renal tissues revealed histopathological changes that validated the biochemical fndings. Compared to HFD group, SOTE and SOHFF treatment led to marked amelioration of all the aforementioned parameters. Collectively, supplementation with SOTE and SOHFF efectively reversed HFD-induced alterations through its antioxidant, hypolipidemic, and anti-infammatory properties. Hence, SOTE and SOHFF have thera- peutic potential in controlling obesity and related pathologies.Item Enhanced cytotoxic activity of beta carotene conjugated liposomes towards breast cancer cell line comparative studies with cyclophosphamide(Wolters Kluwer Health, 01/11/2021) Mahrous, Gina R; Elkholy, Nourhan S; Safwat, Gehan; Medhat, ShafaaThis work aims to evaluate cyclophosphamide (Cyclo) cytotoxic efficacy combined with liposomes in the presence or absence of beta carotene (beta) by detecting the effects of these compounds on the breast cancer cell line (MCF-7) DNA damage. The IC50 value for beta in cytotoxic assay with MCF-7 treated cells was 21.15 μg/ml, while with liposomal beta (LipoBeta) being 121 μg/ml. The free Cyclo IC50 value was 719.86 μg/ml, its liposomal form (LipoCyclo) was 172 μg/ml. The results indicated that in contrast with Cyclo and control values, all comet assay parameters for the LipoBeta were significantly increased (P < 0.05). In MCF-7 cells treated with beta, the findings show a higher intensity of comet tail than those treated with LipoBeta. The presence of several double-strand breaks suggests this high intensity relative to the head. The molecular combination between Cyclo and liposomes in the presence or absence of beta was characterized. Dynamic light scattering measurements confirmed the mono-dispersity of all samples. The incorporation of Cyclo or beta into liposomes exhibited a slight shift to higher temperature compared to the main peak of empty liposomes that exists at 101.5°C which creates a conformational disorder within the phospholipids. The FTIR study showed structural alterations in vesicles after liposome encapsulation.Item The Effect of Alterations in Water Quality Parameters on the Occurrence of Bacterial Diseases in Different Aquatic Environments(Nexus Academic Publishers, 01/11/2021) Khalefa, Hanan S; Abdel-Moneam, Dalia A; Ismael, Elshaimaa; Waziry, Mahmoud Mostafa Fathy; Ali, Mennaallah Samir Gaber; Zaki, Manal MThe current study investigated the influence of adverse water quality parameters in different localities (Qarun Lake, Fayoum Province, Egypt; Mariotteya stream, Giza Governorate, Egypt; and Mediterranean coastal water, Alexandria Governorate, Egypt) on different fish species during the winter. Water and fish samples were collected to evaluate the physicochemical properties and heavy metal distribution in the water. Furthermore, bacteriological analysis of water and fish was performed. The physicochemical characteristics of water samples revealed high conductivity, alkalinity, and higher values of water hardness in Lake Qarun, Fayoum province and Mediterranean coastal water, Alexandria Governorate. However, the parameters in Mariotteya water were within normal limits. Heavy metals were detected in Lake Qarun and the Mediterranean Coast. However, none of the heavy metals analyzed were found in the Mariotteya water samples. Moreover, detected trace elements, cadmium and lead, exceeded the permissible limits. The bacterial load of the collected water samples revealed only the isolation of Escherichia coli and other coliform bacteria from Lake Qarun, while other bacteria included Vibrio spp. (2.48 log10 CFU/mL), Aeromonas spp. (2.70 log10 CFU/mL), and Pseudomonas spp. (3.18, 2.04 log10 CFU/mL) isolated from Lake Qarun and Mariotteya stream, and Staphylococcus spp. (2.00, 1.95, and 1.00 log10 CFU/mL) from Mariotteya stream, Lake Qarun, and Mediterranean Coast, respectively. Among the isolated bacteria from collected fishes, Aeromonas spp. weres detectable at a higher percentage (36.2%) followed by Vibrio spp. (31.4%), Pseudomonas spp. (16.2%), and Staphylococcus spp. (6.7%). Moreover, the highest percentage of bacterial isolates was recovered from Lake Qarun. Large shrimps from the Mediterranean Coast showed a high percentage of Vibrio spp. (40%) isolation. The log of viable microbial count and chemical parameters in water bodies had a strong correlation coefficient (r > 0.75), suggesting that the ecosystem is highly polluted by agricultural and industrial contamination © 2021 Khalefa et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly citedItem Tissue Profile of CDK4 and STAT3 as Possible Innovative Therapeutic Targets in Urinary Bladder Cancer(NLM (Medline), 02/01/2020) Aboushousha, T; Hammam, O; Aref, A; Kamel, A; Badawy, M; Abdel Hamid, ABladder cancer represents a global health problem. It ranks ninth in worldwide cancer incidence. In Egypt, carcinoma of the bladder is the most prevalent cancer, Bladder cancer has the highest recurrence rate of any malignancy. Certainly, suitable molecular diagnostic markers are required to improve the early detection of bladder cancer and then to prolong survival of patients. The present study was aimed to explore the expression of CDk4 and STAT3 in bladder cancer tissues as prospective for target therapy. Our studied groups showed higher values of CDK4 and STAT3 expression in malignant tissues (SCC andUC collectively) compared to cystitis, however, significantly higher values of CDK4 and STAT3 expression were detected in UC group compared to SCC group. Urothelial carcinomas with papillary patterns showed lower parameters of CDK4 and STAT3 expression compared to the non-papillary variant, with significant differences. Higher grades of UC showed significantly higher parameters of CDK4 and STAT3 expression compared to low grade ones. Muscle invasion increases the level of CDK4 and STAT3 expression parameters, compared to non-muscle invasive UC. Conclusion: Our results showed a good correlation of the expression patterns of both the cell cycle (CDK4) and inflammatory (STAT3) markers studied and might be helpful for suggesting more selective agents in the therapeutic scenario of bladder cancer in the near future. Potential biomarkers such as CDK4 andSTAT3 may be targets for molecular based therapeutic strategies in the prevention or management of bladder cancer. Future studies should explore molecular mechanisms of these proteins to define their roles in tumorigenesisItem Insights into the design of inhibitors of the EGFR family with anticancer activity overcoming resistance: a case of optimizing thieno[2,3-d]pyrimidine-based EGFR inhibitors(Elsevier, 02/03/2022) Milik, Sandra N; Abdel-Aziz, Amal Kamal; El-Hendawy, Morad M; El-Gogary, Riham I; Saadeldin, Mona Kamal; Minucci, Saverio; Klein, Christian D; Abouzid, Khaled A.MEGFR inhibitors have been in clinical use for the treatment of non-small cell lung cancer and breast cancer for years. However, generation after generation of the developed EGFR inhibitors have been met by clinical resistance. In an attempt to develop the next generation of EGFR inhibitors, compound (2) was selected as a lead for optimization. (2) was identified during a previous study for the development of thieno[2,3-d]pyrimidine-based dual EGFR/HER2 inhibitors where it demonstrated good dual EGFR/HER2 inhibition and selective anti-proliferative activity against the lapatinib-sensitive cancer cell lines. Additionally, it showed modest activity against the T790M/L858R EGFR mutant. Twelve derivatives based on (2) were designed with the aim of optimizing the enzymatic and cellular activity of (2). Those twelve derivatives were prepared and tested for their inhibitory activities against EGFR, HER2 and T790M/L858R, and for their anti-proliferative activity against the cancer cell lines A431 and MDA-MB-468, and the NCI-60 panel of human cancer cell lines. The results provide an insight into the structural features required for EGFR/HER2 inhibition, and the conclusions drawn from this study could help direct future development of EGFR inhibitors that can overcome the current resistance mechanisms.Item nsights into the design of inhibitors of the EGFR family with anticancer activity overcoming resistance: A case of optimizing thieno[2,3-d]pyrimidine-based EGFR inhibitors(Elsevier, 02/03/2022) Milik, Sandra N; Abdel-Aziz, Amal Kamal; El-Hendawy, Morad M; El-Gogary, Riham I; Saadeldin, Mona Kamal; Minucci, Saverio; Klein, Christian D; Abouzid, Khaled A.MEGFR inhibitors have been in clinical use for the treatment of non-small cell lung cancer and breast cancer for years. However, generation after generation of the developed EGFR inhibitors have been met by clinical resistance. In an attempt to develop the next generation of EGFR inhibitors, compound (2) was selected as a lead for optimization. (2) was identified during a previous study for the development of thieno[2,3-d]pyrimidine-based dual EGFR/HER2 inhibitors where it demonstrated good dual EGFR/HER2 inhibition and selective anti-proliferative activity against the lapatinib-sensitive cancer cell lines. Additionally, it showed modest activity against the T790M/L858R EGFR mutant. Twelve derivatives based on (2) were designed with the aim of optimizing the enzymatic and cellular activity of (2). Those twelve derivatives were prepared and tested for their inhibitory activities against EGFR, HER2 and T790M/L858R, and for their anti-proliferative activity against the cancer cell lines A431 and MDA-MB-468, and the NCI-60 panel of human cancer cell lines. The results provide an insight into the structural features required for EGFR/HER2 inhibition, and the conclusions drawn from this study could help direct future development of EGFR inhibitors that can overcome the current resistance mechanisms. © 2022Item Ecoepidemiology and Potential Transmission of Vibrio cholerae among Different Environmental Niches: An Upcoming Threat in Egypt(MDPI AG, 02/10/2021) Ismail, Eman M; Kadry, Mona; Elshafiee, Esraa A; Ragab, Eman; Morsy, Eman A; Rizk, Omar; Zaki, Manal MCholera is a negative public health event caused by Vibrio cholerae. Although V. cholerae is abundant in natural environments, its pattern and transmission between different niches remain puzzling and interrelated. Our study aimed to investigate the occurrence of nonpathogenic V. cholerae in the natural environment during endemicity periods. It also aimed to highlight the role of molecular ecoepidemiology in mapping the routes of spread, transmission, and prevention of possible future cholera outbreaks. V. cholerae was detected in different aquatic environments, waterfowl, and poultry farms located along the length of the Nile River in Giza, Cairo, and Delta provinces, Egypt. After polymerase chain reaction amplification of the specific target outer membrane gene (Omp W) of suspected isolates, we performed sequence analysis, eventually using phylogenetic tree analysis to illustrate the possible epidemiological relationships between different sequences. Data revealed a significant variation in the physicochemical conditions of the examined Nile districts related to temporal, spatial, and anthropogenic activities. Moreover, data showed an evident association between V. cholerae and the clinically diseased Synodontis schall fish. We found that the environmental distress triggered by the salinity shift and elevated temperature in the Middle Delta of the Nile River affects the pathogenesis of V. cholerae, in addition to the characteristics of fish host inhabiting the Rosetta Branch at Kafr El-Zayat, El-Gharbia province, Egypt. In addition, we noted a significant relationship between V. cholerae and poultry sources that feed on the Nile dikes close to the examined districts. Sequence analysis revealed clustering of the waterfowl and broiler chicken isolates with human and aquatic isolated sequences retrieved from the GenBank databases. From the obtained data, we hypothesized that waterfowl act as a potential vector for the intermediate transmission of cholera. Therefore, continuous monitoring of Nile water quality and mitigation of Nile River pollution, in addition to following good managemental practices (GMPs), general hygienic guidelines, and biosecurity in the field of animal production and industry, might be the way to break this cyclic transmission between human, aquatic, and animal sectors. © 2021 by the author. Licensee MDPI, Basel, Switzerland.Item IL-8 secreted by tumor associated macrophages contribute to lapatinib resistance in HER2-positive locally advanced breast cancer via activation of Src/STAT3/ERK1/2-mediated EGFR signaling(Elsevier, 03/02/2021) Ahmed, Shaza; Taha Mohamed, Hossam; El-Husseiny, Noura; El Mahdy, Manal M; Safwat, Gehan; Diab, Ayman A; El-Sherif, Ahmed A; El-Shinawi, Mohamed; Mohamed, Mona MostafaLocally advanced breast cancer (LABC) is an aggressive disease characterized by late clinical presentation, large tumor size, treatment resistance and low survival rate. Expression of EGFR/HER2 and activation of intracellular tyrosine kinase domains in LABC are associated with poor prognosis. Thus, target therapies such as the anti-receptor tyrosine kinases lapatinib drug have been more developed in the past decade. The response to lapatinib involves the inhibition of RTKs and subsequently signaling molecules such as Src/STAT3/Erk1/2 known also to be activated by the cytokines in the tumor microenvironment (TME). The aim of the present study is to identify the major cytokine that might contribute to lapatinib resistance in EGFR+/HER2+ LABC patients. Indeed, tumor associated macrophages (TAMs) are the main source of cytokines in the TME. Herein, we isolated TAMs from LABC during modified radical mastectomy (MRM). Cytokine profile of TAMs revealed that IL-8 is the most prominent highly secreted cytokine by TAMs of LABC patients. Using in-vitro cell culture model we showed that recombinant IL-8 (50 and 100 ng/mL) at different time intervals interfere with lapatinib action via activation of Src/EGFR and signaling molecules known to be inhibited during treatment. We proposed that to improve LABC patients' response to lapatinib treatment it is preferred to use combined therapy that neutralize or block the action of IL-8.Item Genetic biomarkers predict susceptibility to autism spectrum disorder through interactive models of inheritance in a Saudi community(TAYLOR & FRANCIS AS, 05/03/2019) Bogari, Neda; Dannoun, Anas; Elhawary, Ezzeldin N; Khogeer, Asim; Arab, Arwa H.; Mufti, Ahmad; Rashad, Mona; Qutub, Nermeen; Sindi, Ikhlas A; Tayeb, Mohammed T; Elhawary, Nasser A.Objective: To determine whether individual or interactive single nucleotide polymorphisms (SNPs) may influence the development of autism spectrum disorder (ASD). Methods: DNA from buccal cells of 212 participants (110 cases and 102 controls) were subjected to TaqMan genotyping of the HTR2A rs7997012, HTR2C rs6318, SLC6A4 rs3813034, ANKK1 rs1800497, and BDNF rs6265 SNPs. The ASD symptoms and severity were assessed by DSM-IV criteria and CARS scores. The SNPStats software was used to determine the best interactive model of inheritance of genotypic data. Results: We found susceptibility in ASD cases when compared with controls in rs7997012 (log-additive), rs6318, and rs3813034 (overdominant) and in 1800497 and rs6265 (recessive) (P < 0.05). Heterozygosity significantly contributed to the risk of ASD for rs6318 and rs3813034 SNPs (56%, P = 0.03 and 89%, P = 0.005, respectively). The rs6318 and rs6265 SNPs were significantly associated with cases with CARS scores >= 37 (recessive) (P = 0.03 and P = 0.05, respectively). Both the rs7997012 and rs6265A variant alleles were strongly associated with ASD cases with CARS scores >= 37 (P = 0.005 and P = 0.003). Conclusions: Our study provides clear evidence of associations between all five examined biomarkers and risk for ASD. Achieving exome analyses for Saudi patients with ASD could enable to identify more genetic variants and candidate genes.Item Antiviral activity of chitosan nanoparticles encapsulating curcumin against hepatitis C virus genotype 4a in human hepatoma cell lines(Dove Medical Press Ltd., 05/09/2020) Loutfy, Samah A; Elberry, Mostafa H; Farroh, Khaled Yehia; Mohamed, Hossam Taha; Mohamed, Aya A; Mohamed, ElChaimaa B; Faraag, Ahmed Hassan Ibrahim; Mousa, Shaker AView references (46) Purpose: Current direct-acting antiviral agents for treatment of hepatitis C virus genotype 4a (HCV-4a) have been reported to cause adverse effects, and therefore less toxic antivirals are needed. This study investigated the role of curcumin chitosan (CuCs) nanocomposite as a potential anti-HCV-4a agent in human hepatoma cells Huh7. Methods: Docking of curcumin and CuCs nanocomposite and binding energy calculations were carried out. Chitosan nanoparticles (CsNPs) and CuCs nanocomposite were prepared with an ionic gelation method and characterized with TEM, zeta size and potential, and HPLC to calculate encapsulation efficiency. Cytotoxicity studies were performed on Huh7 cells using MTT assay and confirmed with cellular and molecular assays. Anti-HCV-4a activity was determined using real-time PCR and Western blot. Results: The strength of binding interactions between protein ligand complexes gave scores with NS3 protease, NS5A polymerase, and NS5B polymerase of-124.91,-159.02, and-129.16, for curcumin respectively, and-68.51,-54.52, and-157.63 for CuCs nanocomposite, respec-tively. CuCs nanocomposite was prepared at sizes 29–39.5 nm and charges of 33 mV. HPLC detected 4% of curcumin encapsulated into CsNPs. IC50 was 8 µg/mL for curcumin and 25 µg/ mL for the nanocomposite on Huh7 but was 25.8 µg/mL and 34 µg/mL on WISH cells. CsNPs had no cytotoxic effect on tested cell lines. Apoptotic genes’ expression revealed the caspase-dependent pathway mechanism. CsNPs and CuCs nanocomposite demonstrated 100% inhibition of viral entry and replication, which was confirmed with HCV core protein expression. Conclusion: CuCs nanocomposite inhibited HCV-4a entry and replication compared to curcumin alone, suggesting its potential role as an effective therapeutic agent. © 2020 Loutfy et alItem Plant–microbe–microbe interactions influence the faba bean nodule colonization by diverse endophytic bacteria(Oxford University Press, 05/10/2021) Youseif, Sameh H; Abd El-Megeed, Fayrouz H; Abdelaal, Ali S; Ageez, Amr; Martínez-Romero, EsperanzaLegume root nodules harbor rhizobia and other non-nodulating endophytes known as nodule-associated bacteria (NAB) whose role in the legume symbiosis is still unknown. We analysed the genetic diversity of 34 NAB isolates obtained from the root nodules of faba bean grown under various soil conditions in Egypt using 16S rRNA and concatenated sequences of three housekeeping genes. All isolates were identified as members of the family Enterobacteriaceae belonging to the genera Klebsiella, Enterobacter and Raoultella. We identified nine enterobacterial genospecies, most of which have not been previously reported as NAB. All isolated strains harbored nifH gene sequences and most of them possessed plant growth-promoting (PGP) traits. Upon co-inoculation with an N2 fixing rhizobium (Rlv NGB-FR128), two strains (Enterobacter sichanensis NGB-FR97 and Klebsiella variicola NGB-FR116) significantly increased nodulation, growth and N-uptake of faba bean plants over the single treatments or the uninoculated control. The presence of these enterobacteria in nodules was significantly affected by the host plant genotype, symbiotic rhizobium genotype and endophyte genotype, indicating that the nodule colonization process is regulated by plant-microbe-microbe interactions. This study emphasizes the importance of nodule-associated enterobacteria and suggests their potential role in improving the effectiveness of rhizobial inoculants. © 2021 The Author(s) 2021. Published by Oxford University Press on behalf of FEMS. All rights reserved.Item Anti-diabetic effects of fenugreek (Trigonella foenum-graecum): A comparison between oral and intraperitoneal administration - an animal study(spandidos-publications, 05/12/2020) Baset, Marine E.; Ali, Tasneem I.; Elshamy, Hanan; El Sadek, Ahmed M; Sami, Diana G.; Badawy, Marwa T.; Abou-Zekry, Sara S.; Heiba, Hana H.; Saadeldin, Mona K.; Abdellatif, AhmedHerbal medicine is used by millions of diabetic patients due to economic and cultural factors. The current study investigates the antidiabetic potential of fenugreek (Trigonella foenum-graecum) seed extract at a dose of 100 mg/kg in a Streptozocin-induced diabetic model. Male Sprague-Dawley rats received either intraperitoneal fenugreek [daily (ED) or every other day (EOD)] or oral fenugreek supplement daily, for four weeks. Results show that fenugreek significantly reduced blood glucose. Urea levels were reduced after daily intraperitoneal injection, and creatinine levels dropped after oral treatment, respectively. AST and ALT levels were reduced following fenugreek treatment, while protein levels significantly increased. High-density lipoprotein (HDL) increased after daily injections, while triglycerides decreased significantly in all groups. Glutathione S-transferase and catalase increased with treatment, while peroxidase antioxidant enzyme levels were reduced. Glutathione peroxidase levels increased only after daily injection. Histologically, fenugreek mildly protected hepatic, renal, and pancreatic tissues. In conclusion, the current study shows some potential benefits of fenugreek use. Oral and injectable fenugreek showed improvement in blood glucose, renal and liver functions. Although triglyceride levels decreasedItem Garlic (Allium sativum Linnaeus) improved inflammation and reduced cryptosporidiosis burden in immunocompromised mice(Elsevier, 06/03/2022) Farid, Alyaa; Yousry, Mona; Safwat, GehanEthnopharmacological relevance For thousands of years, garlic (Allium sativum Linnaeus) has been consumed in food and health by numerous civilizations. Cryptosporidium (C.) parvum is an apicomplexan parasite that causes a gastrointestinal disease, with the most common symptoms being watery diarrhea. Although several substances have been tried for its anti-cryptosporidial action, there is no effective treatment for Cryptosporidium disease, especially in immunocompromised individuals. The present study aimed firstly to characterize the bio-active compounds in Allium sativum L. and secondly to evaluate its efficacy as a therapy for cryptosporidiosis especially in immunocompromised mice. Materials and methods This was accomplished by evaluating the parasitological and histopathological parameters in the experimentally infected immunocompetent and immunocompromised mice. Also, the cytokine profile during the experimental time was recorded through the measuring of T helper (h)1, Th2 and Th17 cells cytokines. Immunosuppressed mice were given 0.25 μg/g per day of dexamethasone orally, before infection with Cryptosporidium parvum oocysts, for fourteen consecutive days. Starting 10 days post infection (PI), nitazoxanide (100 mg/kg per day) or Allium sativum (50 mg/kg per day) was given orally for fourteen consecutive days. Results Our results showed that oocyst shedding, on the 32nd day PI, in immunocompromised infected group treated with Allium sativum (354.11, 99.35% PR) showed a significant decrease when compared to its corresponding group treated with nitazoxanide (4369.14, 92.05% PR). On the 32nd day PI, all cytokines levels have been decreased to levels that were similar to those of their uninfected corresponding control groups; also, the histopathological changes and the loss in animals’ body weight had been improved. Treatment with nitazoxanide did not result in infection clearance or a reduction in the increased cytokines' levels. Conclusion Allium sativum L. displayed high efficacy as a potential therapeutic agent against Cryptosporidium, which supports its traditional usage in parasite diseases.Item In vitro and in vivo impacts of nifedipine and diltiazem on praziquantel chemotherapy in murine Schistosoma mansoni(Elsevier, 06/04/2022) Adel Madbouly, Neveen; Emam, Mohammed; Ayman, Malak; Ayman, Mohammed; Rabia, Ibraheem; El Amir, AzzaAim This study was planned to evaluate the in vitro and in vivo antischistosomal effects of the widely used antihypertensive drugs, nifedipine (NIF) and diltiazem (DTZ), and their combinations with praziquantel (PZQ) on early and late Schistosoma (S.) mansoni infections 21- and 45- days old stages. Methods In the In vitro study, Calcium channel blockers (CCBs), NIF and DTZ were added to schistosomula and adult worm cultures in different concentrations 10, 20 and 30 mg/ml. The mortality percentage was calculated 1, 12 and 24 h after incubation. In vivo, NIF and DTZ either alone or combined with PZQ were used to treat male albino mice. The parasitological and total immunoglobulin (Ig) G and IgM anti-soluble egg antigen (SEA) were assessed to demonstrate the disease severity. Results In the In vitro study, 10 mg/ml NIF induced 100% mortality percentage of both schistosomula and adult worms after 24 h incubation, while DTZ induced similar mortality percentage at 30 mg/ml concentration. In vivo results showed that early or late combination of 30 mg/kg of NIF, but not DTZ, significantly (P <0.05) enhanced the reductive efficacy of PZQ based on the parasitological data. The maximal reduction (P <0.05) of anti-SEA IgM and IgG levels was developed during NIF-PZQ administration 21- (1.12 ± 0.06 and 1.09 ± 0.04, respectively) or 45- (1.00 ± 0.03 and 0.8 ± 0.06, respectively) days post infection (PI), compared to either PZQ or NIF individual treatments. The decreased concentration of anti-SEA antibodies was correlated with the diminished granulomatous diameter and disease severity. Conclusion Nifedipine improved PZQ chemotherapy targeting either early or late S. mansoni infection in mice compared to the PZQ mono-therapy. Administering NIF can be considered as a promising drug candidate for schistosomiasis chemotherapy.Item Efficient biocontrol of Spodoptera littoralis by Aspergillus nidulans, an endophyte of Lantana camara(Taylor and Francis Ltd., 06/08/2020) El-Sayed, A.S.A; Moustafa, A.H; El-Sheikh, A.A; Rady, A.M; Fathy, N.A.M; Hussein, H.A; Enan, G; Yassin, M.ASpodoptera littoralis has been recognized as a very destructive polyphagous insect, thus, searching for novel bioagents is the current challenge. Endophytic fungi have been recognized as repertoire for bioactive compounds. Thus, the objective of this work was to isolate endophytic fungi inhabiting Lantana camara and evaluating their insecticidal activity against S. littoralis. Aspergillus nidulans, an endophyte of L. camara, displayed a significant larvicidal activity towards 2nd larval instar of S. littoralis. The morphological identity of A. nidulans has been confirmed from the molecular sequence of ITS region, with genbank accession # MK367603 and deposition # AUMC 14095. The bioactive metabolites of A. nidulans were extracted with EtOAc and DCM and their bioactivity towards S. littoralis was assessed. The values of LC50 were 22.6 and 34.4 µg/mL for dichloromethane and ethylacetate extract, respectively after 18 days of treatment. The chemical identity of insecticidally active compounds was resolved by GC-MS analysis, revealing the presence of major compounds namely 1-docosanol and 1-octadecanol on the EtOAc extract, while cis-9-hexadecenoic acid, and 1-octadecanol were found in the DCM extract. These results indicate that this endophytic fungus could be a potential source for bioactive metabolites and can be used in integrated pest management and other important applications. © 2020, © 2020 Informa UK Limited, trading as Taylor & Francis Group.Item Peganum harmala enhanced GLP-1 and restored insulin signaling to alleviate AlCl3-induced Alzheimer-like pathology model(Springer Nature, 06/08/2021) Saleh, Rofida A; Eissa, Tarek F; Abdallah, Dalaal M; Saad, Muhammed A; El-Abhar, Hanan SPeganum harmala (P. harmala) is a folk medicinal herb used in the Sinai Peninsula (Egypt) as a remedy for central disorders. The main constituents, harmine and harmaline, have displayed therapeutic efficacy against Alzheimer’s disease (AD); however, the P. harmala potential on sensitizing central insulin to combat AD remains to be clarified. An AD-like rat model was induced by aluminum chloride (AlCl3; 50 mg/kg/day for six consecutive weeks; i.p), whereas a methanolic standardized P. harmala seed extract (187.5 mg/kg; p.o) was given to AD rats starting 2 weeks post AlCl3 exposure. Two additional groups of rats were administered either the vehicle to serve as the normal control or the vehicle + P. harmala seed extract to serve as the P. harmala control group. P. harmala enhanced cognition appraised by Y-maze and Morris water maze tests and improved histopathological structures altered by AlCl3. Additionally, it heightened the hippocampal contents of glucagon-like peptide (GLP)-1 and insulin, but abated insulin receptor substrate-1 phosphorylation at serine 307 (pS307-IRS-1). Besides, P. harmala increased phosphorylated Akt at serine 473 (pS473-Akt) and glucose transporter type (GLUT)4. The extract also curtailed the hippocampal content of beta amyloid (Aβ)42, glycogen synthase (GSK)-3β and phosphorylated tau. It also enhanced Nrf2, while reduced lipid peroxides and replenished glutathione. In conclusion, combating insulin resistance by P. harmala is a novel machinery in attenuating the insidious progression of AD by enhancing both insulin and GLP-1 trajectories in the hippocampus favoring GLUT4 production.Item Green Coffea arabica Extract Ameliorates Testicular Injury in High-Fat Diet/Streptozotocin-Induced Diabetes in Rats(Hindawi, 06/12/2020) AL-Megrin, Wafa A.; El-Khadragy, Manal F.; Hussein, Manal H; Mahgoub, Shahenda; Abdel-Mohsen, Doaa M; Taha, Heba; Bakkar, Ashraf A. A; Abdel Moneim, Ahmed E.; Amin, Hatem KDiabetes mellitus (DM) is a chronic endocrine disease characterized by persistent hyperglycemia. Oxidative damage, inflammatory cytokines, and apoptotic cell death play a major role in the induction and progression of male testicular damage. Plant-derived phytochemicals such as green coffee (Coffea arabica) can possess antidiabetic effects with little toxicity. The current study is aimed at investigating the therapeutic roles of green coffee in diabetic testicular injury stimulated by high-fat diet/streptozotocin administration. Diabetes mellitus was induced by a high-fat diet and a single dose of streptozotocin (STZ) (35 mg kg-1) in male albino rats. Diabetic animals were orally given two different concentrations of green coffee (50 mg kg-1 and 100 mg kg-1) for 28 days. The levels of testosterone, luteinizing hormone, and follicle-stimulating hormone and parameters of oxidative stress, inflammation, and apoptosis were measured. mRNAs and protein levels were detected quantitatively by real-time PCR and ELISA, respectively. In the diabetic group, the levels of testosterone, luteinizing hormone, and follicle-stimulating hormone showed a significant reduction while they increased significantly after green coffee treatment. A significant increase of antioxidant markers glutathione, superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase along with decreased levels of lipid peroxides and nitric oxide was observed after green coffee treatment in the diabetic group. Finally, the levels of IL-1β, TNF-α, Bax, and caspase-3 were also decreased in both treated groups (metformin and green coffee) when compared to the diabetic group. We conclude that testicular oxidative impairment induced by a high-fat diet (HFD) and STZ can be reversed by green coffee. Administration of green coffee could represent a promising therapeutic agent which can help the treatment of type 2 DM-induced testicular dysfunction.