Faculty of Biotechnology Research Paper

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Resilient STR loci under gamma radiation: A preliminary study on DNA stability in buccal swabs
(Elsevier Ltd, 2025-03-06) Amani Kraishan; Ahmad M. Refaat; Jenan A. Almhaini; Alaa Saeed Bazuhair; Saeed M. Al-Qahtani; Marwan A. Althomali; Hatem Al-Ameryeen; Ali H. Alomari; Abdul-Wali Ajlouni
This study explores how gamma radiation affects DNA concentration and the stability of autosomal short tandem repeat (STR) markers in buccal swab samples. A total of 160 swabs from 20 volunteers were exposed to therapeutic radiation doses ranging from 1 to 80 Gy. The results revealed a clear dose-dependent decrease in DNA concentration, indicating significant DNA damage as radiation increased. Despite this, the autosomal STR markers remained stable across all doses, demonstrating their robustness against radiation-induced damage. These findings are crucial for clinical and forensic applications, confirming that STR profiling remains reliable for cancer patients undergoing radiation therapy and in forensic cases involving irradiated DNA. The study emphasizes the value of STR markers in genetic analysis under challenging conditions and highlights the need for further research on their long-term stability in diverse biological contexts.
Erbium oxide nanoparticles induce potent cell death, genomic instability and ROS‑mitochondrial dysfunction‑mediated apoptosis in U937 lymphoma cells
(Springer Verlag, 2025-03-22) Hanan R. H. Mohamed; Yusuf Ahmed Elberry; Hagar Magdy; Maryam Ismail; Maivel Michael; Nourhan Eltayeb; Gehan Safwat
Erbium oxide nanoparticles (Er2O3-NPs) have attracted signifcant attention for their unique physicochemical properties, including high surface area, biocompatibility, and stability. However, the impact of Er2O3-NPs on lymphoma cells (LCs) has not been explored, making this an innovative avenue for exploration. Therefore, the current study aimed to explore the infuence of Er2O3-NPs on cell viability, genomic and mitochondrial DNA integrity, reactive oxygen species (ROS) generation and apoptosis induction in human U937 LCs. Er2O3-NPs were characterized using X-ray difraction (XRD) and transmission electron microscopy (TEM). The efect of Er2O3-NPs on cell viability and genomic DNA integrity was estimated after 48 h using the WST-1 cytotoxicity and alkaline Comet assays, respectively. The generation level of reactive oxygen species (ROS) and mitochondrial membrane potential were also analyzed. Flow Cytometry was used to assess apoptosis induction and quantitative RT-PCR was conducted to measure the apoptotic (p53), anti-apoptotic (Bcl2), and mitochondrial (ND3) gene expression. Our results demonstrated the purity and well distribution of Er 2O3-NPs and revealed that Er2O3-NPs induce strong cytotoxicity on U937 cells, as evidenced by a concentration-dependent reduction in cell viability with an IC50 value of 3.20 µg/ml. Exposure of U937 LCs to the IC50 concentration (3.20 µg/ml) of Er2O3-NPs promoted excessive ROS generation, leading to dramatic damage to genomic DNA and mitochondrial membrane potential, as well as marked dysregulation of apoptotic (p53), anti-apoptotic (Bcl2) and mitochondrial ND3 gene expression. This cascade of events triggered both apoptosis and necrosis in Er2O3-NPs-treated U937 LCs. In conclusion, these fndings highlight the strong in vitro cytotoxic potential of Er2O3-NPs against highly aggressive U937 LCs, mediated by excessive ROS production, which leads to severe genomic DNA and mitochondrial membrane damage, as well as profound alterations in apoptotic, anti-apoptotic and mitochondrial gene expression. Future research is needed to further investigate the potential use of Er2O3-NPs in treating lymphoma and to optimize their therapeutic efcacy
Evaluation of the effect of grape seed extract loaded-chitosan nanoparticles on cryptosporidiosis in dexamethasone immunosuppressed male mice
(Elsevier B.V, 2025-02-25) Karim Tarek; Gehan Safwat; Alyaa Farid
Cryptosporidiosis is a worldwide health problem that results in an economic loss. The disease is caused by the protozoan Cryptosporidium spp. Individuals with suppressed immunity, like those with organ transplantation, cancer and human immunodeficiency virus syndrome, suffer from the infection that may lead to the death. Nitazoxanide (NTZ) is the approved FDA treatment for cryptosporidiosis in immunocompetent individuals. There is an urgent need to find a new natural treatment that can replace NTZ in immunosuppressed hosts. The study aimed to use grape seed extract loaded chitosan nanoparticles (GSEx-CHNPs) in treatment of cryptosporidiosis in immunosuppressed male mice. GSEx was prepared by the alcoholic extraction method followed by the identification of its bioactive components. GSEx-CHNPs were synthesized by ionic gelation method and physically characterized then their activities were examined in vitro. The experimental groups, included immunocompetent and immunosuppressed groups, was treated with NPs for 14 days post infection (PI). The results showed the presence of many phenolic compounds in the GSEx. GSEx-CHNPs significantly improved the loss in animals body weight, cleared the infection and amolerated the serum cytokines levels. GSEx-CHNPs showed anti-cryptosporidial activity especially in immunosuppressed mice model. Where, it amolerated the disturbance in the cytokine profile leading to an anti-inflammatory response.
Calcium titanate nanoparticlesinduced cytotoxicity, genotoxicity and oxidative stress in human nonsmall lung cancer cells
(Nature Publishing Group, 2025-02-21) Hanan R. H. Mohamed; Shahd E. E. Shaheen; Esraa H. Ibrahim; Nesma O. E. Hussein; Gehan Safwat
Calcium titanate nanoparticles (CaTiO3NPs) have garnered significant attention due to their unique properties and excellent biocompatibility, which have led to their increased use in various fields and consumer products. This rise in application necessitates a better understanding of their biological and toxicological effects. However, there is limited data on the cytotoxicity and genotoxicity of CaTiO3NPs in human normal skin fibroblasts (HSF) and non-small lung cancer (A-549) cells. Consequently, this study aimed to explore the effect of 48-hour exposure to CaTiO3NPs on cell viability, genomic DNA integrity, and oxidative stress induction in human cancer A-549 cells, compared to normal HSF cells. The cytotoxicity and genotoxicity of CaTiO3NPs were assessed using the Sulforhodamine B (SRB) cytotoxicity and Alkaline Comet assays, respectively. To estimate possible oxidative stress induction and variation in apoptotic gene expression, reactive oxygen species (ROS) analysis and quantitative real-time polymerase chain reaction (qRT-PCR) were also performed. Our findings demonstrated that exposure to CaTiO3NPs for 48 h resulted in low toxicity toward both normal HSF and cancer A-549 cells, with cell death observed only at high concentrations (100 and 1000 µg/ml). The IC50 value of CaTiO3NPs in both HSF and A-549 cells was greater than 1000 µg/ml; specifically, the IC50 value in A-549 cells at 48 h was 1670.65 µg /ml. However, treatment with CaTiO3NPs for 48 h at the IC50 concentration of 1670.65 µg /ml resulted in significant genomic DNA damage and excessive ROS generation, along with a notable disturbance in the expression level of apoptotic (p53 and Bax) and anti-apoptotic Bcl2 genes in A-549 cells. In contrast, no significant changes were observed in HSF cells treated for 48 h with the same concentration (1670.65 µg /ml) of CaTiO3NPs. Collectively, these findings indicated that despite short-term exposure to CaTiO3NPs causing low cytotoxicity in both normal HSF and A-549 cells. CaTiO3NPs were selectively genotoxic toward A-549 cells. This genotoxicity was mediated through excessive ROS generation, which disrupted genomic DNA integrity and altered the expression of apoptotic genes, triggering apoptosis in A-549 cells. Further in vitro and in vivo studies are needed to fully understand the toxicological and biological properties of CaTiO3NPs.
Purifcation and Immobilization of Burkholderia gladioli Cholesterol Oxidase on Calcium Alginate, with Robust Catalytic Stability for Cholesterol Oxidation In Vitro
(Springer New York, 2025-02-05) Ashraf S. A. El‑Sayed; Ahmed A. Shindia; Walaa M. El‑Badry; Ahmed A. Mostafa; Abdullah A.Al‑Ghanayem; Amgad M. Rady
Cholesterol oxidase (COX) is a key enzyme in diagnostic kits of cardiovascular diseases via oxidation of cholesterol producing smart enantiomerically compounds; however, the enzyme catalytic stability is the challenge. So, the objective of this study was to purify COX from novel endophytic bacterial isolates of medicinal plants that could have unique catalytic efciency for the desired applications. Among the recovered forty bacterial isolates, Burkholderia gladioli EFBL PQ721377, an endophyte of Eruca sativa, had the highest COX productivity (14.7 μmol/mg/min). The COX productivity of B. gladioli has been maximized by with the response surface methodology, giving the highest productivity 30.9 μmol/mg/min, by ~2.0-fold increment compared to control. The enzyme was purifed to its molecular homogeneity with subunit structure 40 kDa. The enzyme was entrapped in Ca-alginate with immobilization yield 87.5%, and the efciency and homogeneity in Ca-alginate beads were assessed by FTIR and SEM–EDX analyses. The free and Ca-alginate-COX conjugates have the same maximum reaction temperature at 37–40 °C, reaction pH at 7.5 and pH stability at 6.5–8.0. The thermal stability of Ca-alginate-COX was increased by ~ 7.0 folds compared to the free one, ensuring the protective role of alginate beads on enzyme tertiary structure. Ca-alginate-COX had a higher potency of oxidation of human serum cholesterol, than the free one, confrming the feasibility of the product release, and allosteric activation of the enzyme, with a reliable operative stability till the ffth cycle, for production of cholest-4-en-3-one, as the precursor of various drugs.
Deciphering the Interplay of the PD-L1/MALT1/miR-200a Axis During Lung Cancer Development
(Wiley-Blackwell, 2025-01-05) Sherien M. El-Daly; Sahar S. Abdelrahman; Mona A. El-Bana; Yasmin Abdel-Latif; Dalia Medhat; Safaa M. Morsy; Hanaa A. Wafay
Lung cancer remains a leading cause of cancer-related mortality worldwide. Our study investigates the involvement of the PD-L1/MALAT1/miR-200a-3p axis in lung tumor progression using a murine model of lung carcinogenesis. Lung tumors were induced in rats, which were divided into groups and sacrificed at different stages of tumor development. A histopathological examination was performed to assess tumor progression. Immunohistochemistry was applied to evaluate the expression of Ki-67 and programmed death-ligand 1 (PD-L1). The level of carcinoembryonic antigen (CEA) and expression analysis of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), miR-200a-3p, and zinc finger E-box binding homeobox 1 (ZEB1) were evaluated for each stage of induction. Immunohistochemical analysis demonstrated a progressive upregulation of the proliferative marker Ki-67 and the immune checkpoint protein PD-L1 during the induction process, indicative of enhanced tumor proliferation and immune evasion. Additionally, CEA levels revealed a progressive increase across induction stages, with a significant increase in advanced tumor stages, highlighting its clinical relevance as a biomarker for lung cancer progression. Expression analysis revealed dynamic upregulation of MALAT1 and downregulation of miR-200a during lung tumor induction, which correlated with advanced tumor stages and elevated PD-L1 expression, suggesting that the negative correlation between MALAT1 and miR-200a is involved in the development of lung tumors. ZEB1 expression exhibited a notable increase in the advanced stages of induction, consistent with its association with aggressive lung cancer. Our findings underscore the interplay between molecular pathways involved in lung tumor development and the potential diagnostic and therapeutic implications of the PD-L1/MALAT1/miR-200a-3p axis.
Egyptian Novel Goose Parvovirus in Immune Organs of Naturally Infected Ducks: Next-Generation Sequencing, Immunohistochemical Signals, and Comparative Analysis of Pathological Changes Using Multiple Correspondence and Hierarchical Clustering Approach
(Multidisciplinary Digital Publishing Institute (MDPI), 2025-01-13) Mohamed A. Lebdah; Amal A. M. Eid; Reham M. ElBakrey; Abd Elgalil. El-Gohary; Mohamed G. Seadawy; Mohamed R. Mousa; Hagar F. Gouda; Nehal I. A. Goda; Mostafa F. El-Hosseny; Ahmed S. El-tahlawy; Rokayya Sami; Rasha A. Al-Eisa; Sarah S. Helal
The present study aims to better understand the nature of currently circulating GPV strains and their pathological impact on the immune system during natural outbreaks among different duck breeds in Egypt. For this purpose, 99 ducks (25 flocks) of different breeds, aged 14–75 days, were clinically examined, and 75 tissue pools from the thymus, bursa of Fabricius, and spleen were submitted for virus detection and identification. Clinical and postmortem findings were suggestive of GPV infection. Concerning the immune system organs, atrophy in the thymus (60.6%), bursa (45.5%), and spleen (38.3%) was the most common gross lesion. Microscopically, the pathological impact of the virus was exhibited by a necrotic thymic cortex with Hassall’s corpuscle disintegration, the disappearance of normal bursal histological morphology accompanied by atrophied follicles and lymphocytic depletion, and apoptosis of B-lymphocytes in lymphoid follicles of the spleen. Furthermore, immunohistochemical examination revealed positive signals of the parvovirus detected in thymic lymphocytes in the cortex, bursa-dependent lymphoid follicle of the medulla, and diffuse positive expression of viral antigens in the spleen. GPV was detected in ducks using polymerase chain reaction, with the highest percentage of positive detection in the bursa of Fabricius (76%). Next-generation sequencing and phylogenetic analysis revealed that the detected virus was a variant of GPV, globally named novel GPV (NGPV), and closely related to Chinese NGPV isolates. To our knowledge, the current study is pioneering to address the immunopathological impact of NGPV among naturally infected ducks confirmed with full genome sequencing and immunohistochemical identification worldwide.
Genome-wide identifcation of MGT gene family in soybean (Glycine max) and their expression analyses under magnesium stress conditions
(BioMed Central Ltd, 2025-01-23) Ammar Anwar; Junaid Akhtar; Saba Aleem; Maida Aleem; Muhammad Khuram Razzaq; Saud Alamri; Qasim Raza; Iram Sharif; Arooj Iftikhar; Shehreen Naseer; Zaheer Ahmed; Iqrar Ahmed Rana; Waheed Arshad; Muhammad Imran Khan; Javaid Akhter Bhat; Muqadas Aleem; Abdel-Rhman Z. Gaafar; Mohamed S. Hodhod
Background Magnesium (Mg) is essential for plant growth and development and plays critical roles in physiological and biochemical processes. Mg defciency adversely afects growth of plants by limiting shoot and root development, disturbing the structure and membranes of the grana, reducing photosynthesis efciency, and lowering net CO2 assimilation. The MGT (Magnesium transporter) family isresponsible for the absorption and transportation of magnesium in plants. Although the MGT family has been identifed in diferent plant species, research regarding the soybean MGT genes islimited. Results In the current study, a total of 39 MGT genes distributed on 17 diferent chromosomes were identifed in soybean. Phylogenetic analysis classifed GmMGTs into three subgroups, NIPA, MRS2/MGT, and CorA, which showed little homology with MGTs of Arabidopsis thaliana and Oryza sativa members and clustered tightly with GmMGTs. Gene structure and conserved motif analysis also confrmed similar grouping in GmMGTs. The expansion of the GmMGT members in NIPA and MRS2/MGT was predicted, while CorA was identifed as the most conserved group in G. max. Segmental duplication under purifying selection pressure was identifed as the major driving force in the expansion of MGTs in soybean. GmMGTs showed diverse tissue-specifc and stress-response expression patterns due to the presence of stress-related cis-regulatory elements in their promoter regions. Under Mg-defciency and surplus stress conditions, a decrease in root length, shoot length, and root and shoot fresh as well dry weight in susceptible genotypes showed the variegated expression of MGTs in soybean genotypes. Furthermore, the upregulation of GmMGT2 and GmMGT29 in tolerant genotypes in response to Mg-defciency as well as surplus stress conditions in leaves suggested the essential role of GmMGT genes in the absorption and transportation of Mg in soybean leaves. Conclusion This study presents a comprehensive analysis of the MGT gene family in soybean, providing insights into their evolutionary relationships, gene classifcation, protein structures, and expression patterns under both Mg defciency and Mg surplus conditions.
Calcium hydroxide nanoparticles induce cell death, genomic instability, oxidative stress and apoptotic gene dysregulation on human HepG2 cells
(Nature Publishing Group, 2025-01-23) Hanan R. H. Mohamed; Esraa H. Ibrahim; Shahd E. E. Shaheen; Nesma O. E. Hussein; Ayman Diab; Gehan Safwat
Calcium hydroxide nanoparticles (Ca(OH)2NPs) possess potent antimicrobial activities and unique physical and chemical properties, making them valuable across various fields. However, limited information exists regarding their effects on genomic DNA integrity and their potential to induce apoptosis in normal and cancerous human cell lines. This study thus aimed to evaluate the impact of Ca(OH)2NPs on cell viability, genomic DNA integrity, and oxidative stress induction in human normal skin fibroblasts (HSF) and cancerous hepatic (HepG2) cells. Cell viability and genomic DNA stability were assessed using the Sulforhodamine B (SRB) assay and alkaline comet assay, respectively. Reactive oxygen species (ROS) levels were measured using 2,7-dichlorofluorescein diacetate, while the expression level of apoptosis-related genes (p53, Bax, and Bcl-2) were quantified using real-time PCR (qRT-PCR). The SRB cytotoxicity assay revealed that a 48-hour exposure to Ca(OH)2NPs caused concentration-dependent cell death and proliferation inhibition in both HSF and HepG2 cells, with IC50 values of 271.93 µg/mL for HSF and 291.8 µg/mL for HepG2 cells. Treatment with the IC50 concentration of Ca(OH)2NPs selectively induced significant DNA damage, excessive ROS generation, and marked dysregulation of apoptotic (p53 and Bax) and anti-apoptotic (Bcl-2) gene expression in HepG2 cells, triggering apoptosis. In contrast, exposure of HSF cells to the IC50 concentration of Ca(OH)2NPs caused no significant changes in genomic DNA integrity, ROS generation, or apoptotic gene expression. These findings indicate that Ca(OH)2NPs exhibit concentrationdependent cytotoxicity in both normal HSF and cancerous HepG2 cells. However, exposure to the IC50 concentration was non-genotoxic to normal HSF cells while selectively inducing genotoxicity and apoptosis in HepG2 cancer cells through DNA breaks and ROS-mediated mechanisms. Further studies are required to explore the biological and toxicological properties and therapeutic potential of Ca(OH)2NPs in hepatic cancer treatment.
Cobalt oxide nanoparticles induce cytotoxicity and excessive ROS mediated mitochondrial dysfunction and p53-independent apoptosis in melanoma cells
(Nature Publishing Group, 2025-01-06) Hanan R. H. Mohamed; Basma A. Mohamed; George M. Hakeem; Shahd H. Elnawasani; Maria Nagy; Rawan Essam; Ayman Diab; Gehan Safwat
Nanotherapy has emerged as a promising strategy for the targeted and efficient treatment of melanoma, the most aggressive and lethal form of skin cancer, with minimized systemic toxicity. However, the therapeutic efficacy of cobalt oxide nanoparticles (Co3O4NPs) in melanoma treatment remains unexplored. This study aimed to assess the therapeutic potential of Co3O4NPs in melanoma treatment by evaluating their impact on cell viability, genomic DNA and mitochondrial integrity, reactive oxygen species (ROS) generation and apoptosis induction in melanoma A-375 cells. Our findings demonstrated a concentration-dependent reduction in cell viability upon treatment with five Co3O4NP concentrations (0.2, 2, 20, 200, and 2000 µg/ml), with an IC50 value of 303.80 µg/ml. Treatment with this IC50 concentration significantly increased ROS generation, induced dramatic DNA damage, and disrupted mitochondrial membrane potential integrity. Flow cytometric analysis revealed apoptosis and necrosis induction following Co3O4NP exposure at the IC50 concentration value. Results of qRT-PCR analysis demonstrated remarkable dysregulation of apoptotic and mitochondrial genes, including a significant downregulation of apoptotic p53 and mitochondrial ND3 genes and marked upregulation of the anti-apoptotic gene Bcl2. These findings highlight the novel potential of Co3O4NPs as potent inducers of melanoma A-375 cell death in a concentration-dependent manner through excessive ROS production, genomic instability, mitochondrial dysfunction and dysregulation of apoptotic and mitochondrial gene expression, ultimately promoting apoptosis in A-375 cells. This study thus underscores the potential of Co3O4NPs as a promising nanotherapeutic candidate for melanoma treatment, warranting further exploration to elucidate their full biological and clinical applicability.
Decoding Parkinson's disease: A multifaceted approach to diagnosis and biomarker discovery
(Elsevier, 2024-01-01) Mahmoud Ragab; Al-Hassan Soliman; Abd El-Rahman Shaltout; Toka Aziz El-Ramly; Mariam Morris; Omar Abdelnasser A. Mohamed; Roqaia Ibrahim; Duaa Dakhlaah
We all get older, and our brains get older, but only some of us get neurodegenerative disorders like Parkinson's disease (PD). Age, which is a dynamic process, is the largest risk factor for the development and progression of PD. Decreased dopaminergic activity, tangential Lewy body illnesses, and degenerative pathologies are predisposing factors leading to PD. Due to the significant clinical overlap across parkinsonian illnesses, the misdiagnosis rate is still high (16%-20%) even when the new diagnostic standards are correctly applied. Misdiagnosis and delayed diagnosis militate against the therapeutic benefits of disease-modifying therapies. Thus, there is an urgent need to discover and develop precise and reliable PD biomarkers. Discovering accurate biomarkers for early diagnoses, such as prodromal diagnosis and preclinical diagnosis, is necessary for better clinical intervention and treatment at the onset of disease. Further, these reliable biomarkers can be used to evaluate the progression of PD disorder. In this book chapter, we will discuss current progress in the development of PD biomarkers from various perspectives including imaging biomarkers, clinical, genetic, RNA-based biomarkers, biochemical, metabolomics, artificial intelligence, deep learning, and machine learning aspects that play critical roles as diagnostic biomarkers for PD. © 2025 Elsevier Inc. All rights reserved
THE EFFICACY OF DIZYGTHECA KERCHOVEANA AND AZADIRACHTA INDICA EXTRACTS AS A MOLLUSCICIDAL AND SCHISTOSOMICIDAL AGENTS IN MICE
(Egyptian Society of Parasitology, 2020-04-02) AZZA M. EL AMIR; ALYAA A. FARID; MARIAM MOHAMED; WAAD RAMADAN; AYMAN ALI DIAB
In the present study, the effect of methanol extracts of two plant species, Dizygotheca kerchoveana (Maliaceae) and Azadirachta indica (Araliacaea) were tested on the activity of Schistosoma mansoni worms. Efficacy of two plant extracts compared with praziquantel (PZQ) was evaluated in vivo. The results showed that reduction was 90% in case of PZQ treatment compared to 76.91%, 62.64% after treatment with D. kerchoveana and A. indica extracts respectively. PZQ recorded highest significant number of dead ova into oogram pattern (80±1.80) at 5wk PI. But, good results were obtained by of D. kerchoveana and A. indica methanol extracts (65.00±4.05 & 60.60±3.60, respectively) at 3wk PI. Efficacy of the plant extract showed a significant (P<0.01) reduction in ova to 91-96.20% in intestine, 83.36-91.24% in hepatic tissues as compared to PZQ (10-66.50% & 1.14-80.64%, respectively). Reduction in hepatic granuloma diameter at 3wk PI was significantly (P<0.01) reduced in group treated with D. kerchoveana (40.43% & 38.30%) as compared to PZQ (8.70% & 11.7%). Sera were assayed by ELISA for IgM & IgG levels. Highly significant (P<0.01) increase in Igs levels in all infected treated or untreated groups was at 3wk & 5wk PI as compared to normal mice.
Navigating the COVID-19 Therapeutic Landscape: Unveiling Novel Perspectives on FDA-Approved Medications, Vaccination Targets, and Emerging Novel Strategies
(Multidisciplinary Digital Publishing Institute (MDPI), 2024-11-25) Reham F. Barghash; Donato Gemmati; Ahmed M. Awad; Mustafa M. M. Elbakry; Veronica Tisato; Kareem Awad; Ajay Vikram Singh
Amidst the ongoing global challenge of the SARS-CoV-2 pandemic, the quest for effective antiviral medications remains paramount. This comprehensive review delves into the dynamic landscape of FDA-approved medications repurposed for COVID-19, categorized as antiviral and non-antiviral agents. Our focus extends beyond conventional narratives, encompassing vaccination targets, repurposing efficacy, clinical studies, innovative treatment modalities, and future outlooks. Unveiling the genomic intricacies of SARS-CoV-2 variants, including the WHO-designated Omicron variant, we explore diverse antiviral categories such as fusion inhibitors, protease inhibitors, transcription inhibitors, neuraminidase inhibitors, nucleoside reverse transcriptase, and non-antiviral interventions like importin α/β1-mediated nuclear import inhibitors, neutralizing antibodies, and convalescent plasma. Notably, Molnupiravir emerges as a pivotal player, now licensed in the UK. This review offers a fresh perspective on the historical evolution of COVID-19 therapeutics, from repurposing endeavors to the latest developments in oral anti-SARS-CoV-2 treatments, ushering in a new era of hope in the battle against the pandemic.
Influence of Vitamin D Status and the VDR Gene Polymorphism on COVID-19 Susceptibility and Outcome
(Journal of Pure and Applied Microbiology, 2024-11-26) Amal Ahmed Mohamed; Nivin Naeem Baiomy; Abeer M. Rawy; Mona M.F. Ghanem; Soha M. Abd El Salam; Karima Nasraldin; Mohamed Ramadan Ezz Al Arab; Hussein H. Samir; Omar Mohamoud Azzam; Nashwa M. Muharram; Naglaa Elsalway; Ahmed Y. Elamir; Sarya Swed; Wael Hafez; Luis A. Salas-Matta; Alfonso J. Rodriguez-Morales; D. Katterine Bonilla-Aldana; Hashem Abu Serhan; Sanjit Sah; Rachana Mehta
Insufficient vitamin D levels in the bloodstream, together with the presence of specific genetic variations known as single nucleotide polymorphisms (SNPs) within the VDR gene, have consistently been linked to a higher likelihood of contracting and experiencing more severe forms of various diseases such as the ongoing COVID-19 pandemic. We aimed to explore the potential relationship between vitamin D levels, Bsml and FoKI polymorphisms, and COVID-19 infection outcomes. A case-control study was conducted with COVID-19 patients and a control group of non-COVID-19 patients (n = 107 each). The associations between vitamin D status, polymorphisms, and COVID susceptibility were investigated. Participants diagnosed with COVID-19 exhibited an average age of 48.84 ± 12.18, while non-COVID-19 patients had an average age of 46.82 ± 9.903. Disease severity, assessed by the CT severity score, showed a negative correlation with the Vitamin D levels. Among participants with COVID-19, the mean level of vitamin D was 35.25 ± 9.40 ng/mL while non-COVID-19 patients showed 38.85 ± 9.40 ng/mL with a significant difference (p = 0.004**) although among COVID-19 cases, 87 (81.3%) individuals had sufficient vitamin D levels and non-severity of disease was more common i.e. 54 (50.5%) among the COVID patients who had sufficient level of Vitamin D. The study found no significant association between Vitamin D levels and rs1544410 Bsml polymorphism (p = 0.429). However, it is important to highlight a weak significant association observed between with Fok1 polymorphism (p = 0.049). These findings underscore the weak influence of genetic factors, particularly VDR Fok1 gene variants, in shaping an individual’s susceptibility to COVID-19. A significant difference in vitamin D status was observed between the COVID-19 and non-COVID-19 groups and lower level was observed in the COVID-19 infected patients. Furthermore, a weak significant association was observed between Fok1 rs2228570 genotype and COVID-19 susceptibility. Larger sample sizes are required to comprehensively understand the association between different genotypes and COVID-19 outcomes.
Emerging roles of hydrogen sulfide-metabolizing enzymes in cancer
(Taylor and Francis, 2024-12-02) Alyaa Dawoud; Rana A. Youness; Kareem Elsayed; Heba Nafae; Hoda Allam; Hager Adel Saad; Carole Bourquin; Csaba Szabo; Reham Abdel-Kader; Mohamed Z. Gad
Gasotransmitters play crucial roles in regulating many physiological processes, including cell signaling, cellular proliferation, angiogenesis, mitochondrial function, antioxidant production, nervous system functions and immune responses. Hydrogen sulfide (H2S) is the most recently identified gasotransmitter, which is characterized by its biphasic behavior. At low concentrations, H2S promotes cellular bioenergetics, whereas at high concentrations, it can exert cytotoxic effects. Cystathionine β-synthetase (CBS), cystathionine-γ-lyase (CSE), 3-mercaptopyruvate sulfurtransferase (3-MST), and cysteinyl-tRNA synthetase 2 (CARS2) are pivotal players in H2S biosynthesis in mammalian cells and tissues. The focus of this review is the regulation of the various pathways involved in H2S metabolism in various forms of cancer. Key enzymes in this process include the sulfide oxidation unit (SOU), which includes sulfide:quinone oxidoreductase (SQOR), human ethylmalonic encephalopathy protein 1 (hETHE1), rhodanese, sulfite oxidase (SUOX/SO), and cytochrome c oxidase (CcO) enzymes. Furthermore, the potential role of H2S methylation processes mediated by thiol S-methyltransferase (TMT) and thioether S-methyltransferase (TEMT) is outlined in cancer biology, with potential opportunities for targeting them for clinical translation. In order to understand the role of H2S in oncogenesis and tumor progression, one must appreciate the intricate interplay between H2S-synthesizing and H2S-catabolizing enzymes.
Prognostic impact of matrix metalloproteinase 2 (MMP-2) and matrix metalloproteinase 9 (MMP-9) in Egyptian breast cancer patients
(SAGE Publications Inc, 2024-11-12) Fayrouz A Fouad1,2 , Mohamed A Khali3 , Inas Moaz4, Hossam Elmasry1 , Nada Gheta5, Asala Abdeen5, Mariam Tantawi5, Ganna Elkholy5, Shaimaa Rihan6, Mahmoud M Kamel3 , Ayman EL-Meghawry EL-Kenawy7, Youssef AS Abdel-Moneim8 and Abdallah M Gameel; Fayrouz A Fouad; Mohamed A Khali; Inas Moaz; Hossam Elmasry; Nada Gheta; Asala Abdeen; Mariam Tantawi; Ganna Elkholy; Shaimaa Rihan; Mahmoud M Kamel; Ayman EL-Meghawry EL-Kenawy; Youssef AS Abdel-Moneim; Abdallah M Gameel
This study aims to investigate the diagnostic and prognostic relevance of MMP-2 and MMP-9 as biomarkers for breast cancer, as well as their association with clinicopathological factors. Breast cancer is a leading contributor to cancerrelated deaths among women worldwide. The discovery of biomarkers is crucial for early diagnosis, outcome prediction, and effective treatment. Matrix metalloproteinases (MMPs) play a significant role in various physiological and pathological activities, including development, tissue repair, inflammation, cancer spread, and metastasis. While the prognostic significance of MMP-2 and MMP-9 levels in breast cancer has been studied, the findings remain inconclusive. Participants were divided into three groups, with each group consisting of 62 individuals: Group I comprised healthy controls, Group II consisted of newly diagnosed breast cancer patients (stage I-III), and Group III included patients with metastatic breast cancer. Levels of MMP-2 and MMP-9 were evaluated in these groups using the ELISA method. An evident increase in MMP-2 and MMP-9 levels was noted when comparing the control group with both the breast cancer and metastatic groups. Furthermore, a notable correlation was identified between serum MMP-9 levels and the pathological diagnosis of breast cancer (P<0.001) as well as tumor size (P<0.01). MMP-2 and MMP-9 have emerged as promising biomarkers for breast cancer, with MMP-9 specifically associated with disease prognosis. Continued investigation into the anti-tumor mechanisms of MMPs may yield significant advancements in the development of targeted therapeutic strategies for the management of breast cancer.
Retinoic acid inhibition of cell proliferation via activation of CDKN1B signaling in the forebrain and spinal cord during mouse embryonic development
(Springer Science and Business Media Deutschland GmbH, 2024-12-03) Ahmed Said; Amira S. AbdElkhalek; Mariam Sherief; Lydia Amir; Maysem Samy; Mariam S. Nabil; Gehan Safwat; Ayman A. Diab; Karima Nasraldin
Background: The active metabolite of vitamin A (retinol) is retinoic acid (RA). RA is essential for developing several organs as a signaling molecule that is tightly regulated during embryogenesis. We explored the teratogenic effects of RA on forebrain and spinal cord development modified by cyclin-dependent kinase inhibitor 1B (CDKN1B), as the mechanism underlying RA's teratogenic impacts requires further investigation. The study involved four groups of pregnant mice: the negative control group, the positive control group treated with dimethyl sulfoxide (DMSO) diluted in sunflower oil, the RA-treated group receiving a low dosage (5 mg/kg), and the RA-treated group receiving a high dosage (10 mg/kg). The treatment groups received daily intraperitoneal RA dissolved in DMSO and diluted with sunflower oil on gestational days 10.5, 11.5, and 12.5. On day 13.5 of pregnancy, the pregnant mice were euthanized by cervical dislocation, and immunohistochemical analyses of brain and spinal cord tissues were performed. Results: Morphologically, we observed a decrease in the number of implantation sites and the presence of hematomas in several uterus areas in the high-dose RA (10 mg/kg) group. Additionally, RA was shown to cause adverse changes in uterine weight and length. RA treatment indicated elevated levels of CDKN1B expression in spinal cord development, the diencephalon, and the telencephalon. Conclusion: Our findings demonstrated that by activating CDKN1B as an RA target gene for cell cycle arrest, an excess of RA during brain development in mouse embryos can induce cell undifferentiation during development.
Using MaxEnt modeling to analyze climate change impacts on Pseudomonas syringae van Hall, 1904 distribution on the global scale
(Elsevier B.V, 2024-12-07) Sameh M.H. Khalaf; Monerah S.M. Alqahtani; Mohamed R.M. Ali; Ibrahim T. I. Abdelalim; Mohamed S. Hodhod
Pseudomonas syringae is a pathogenic bacterium that poses a significant threat to global agriculture, necessitating a deeper understanding of its ecological dynamics in the context of global warming. This study investigates the current and projected future distribution of P. syringae, focusing on the climatic factors that influence its spread. To achieve this, we employed Maximum Entropy (MaxEnt) modeling based on Geographic Information Systems (GIS) to analyze species occurrence records alongside relevant climate data. The MaxEnt model was calibrated using 75 % of the occurrence data, with the remaining 25 % reserved for validation. The model’s performance was meticulously assessed utilizing the area under the curve (AUC) and true skill statistics (TSS), resulting in an AUC score of 0.92, indicating excellent predictive capability. Our analysis identified key climatic parameters—temperature, precipitation, and humidity—that significantly affect the presence of P. syringae. Notably, our findings project an expansion of the bacterium’s geographic range in the coming decades, with optimal conditions shifting toward the poles. This research underscores the significant influence of climate change on the distribution of P. syringae and provides valuable insights for developing targeted disease management strategies. The anticipated increase in bacterial infections in crops highlights the urgent need for proactive measures to mitigate these effects.
Metabolic modelling links Warburg effect to collagen formation, angiogenesis and inflammation in the tumoral stroma
(Public Library of Science, 2024-12-03) Maxime MahoutI; Laurent Schwartz; Romain Attal; Ashraf Bakkar; Sabine Peres
Cancer cells are known to express the Warburg effect—increased glycolysis and formation of lactic acid even in the presence of oxygen—as well as high glutamine uptake. In tumors, cancer cells are surrounded by collagen, immune cells, and neoangiogenesis. Whether collagen formation, neoangiogenesis, and inflammation in cancer are associated with the Warburg effect needs to be established. Metabolic modelling has proven to be a tool of choice to understand biological reality better and make in silico predictions. Elementary Flux Modes (EFMs) are essential for conducting an unbiased decomposition of a metabolic model into its minimal functional units. EFMs can be investigated using our tool, aspefm, an innovative approach based on logic programming where biological constraints can be incorporated. These constraints allow networks to be characterized regardless of their size. Using a metabolic model of the human cell containing collagen, neoangiogenesis, and inflammation markers, we derived a subset of EFMs of biological relevance to the Warburg effect. Within this model, EFMs analysis provided more adequate results than parsimonious flux balance analysis and flux sampling. Upon further inspection, the EFM with the best linear regression fit to cancer cell lines exometabolomics data was selected. The minimal pathway, presenting the Warburg effect, collagen synthesis, angiogenesis, and release of inflammation markers, showed that collagen production was possible directly de novo from glutamine uptake and without extracellular import of glycine and proline, collagen’s main constituents. Copyright: © 2024 Mahout et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Novel goose parvovirus in naturally infected ducks suffering from locomotor disorders: molecular detection, histopathological examination, immunohistochemical signals, and full genome sequencing
(Taylor and Francis Ltd, 2024-11-20) Mohamed A. Lebdah; Amal A. M. Eid; Reham M. ElBakrey; Abd Elgalil. El-Gohary; Mohamed R. Mousa; Hagar F. Gouda; Ahmed F. Gad; Sarah S. Helal; Mohamed G. Seadawy
In this study, we investigated the pathological effects of novel goose parvovirus (NGPV) infection on the skeletal muscle, brain, and intestine of naturally affected ducks suffering from locomotor dysfunction as a new approach for a deeper understanding of this clinical form. For this purpose, a total of 97 diseased ducks, representing 24 flocks of different duck breeds (14–75 days old), were clinically examined. In total, 72 tissue pools of intestine, brain, and skeletal muscle samples were submitted for molecular identification. Typical clinical signs among the examined ducks suggested parvovirus infection. Regarding postmortem examination, all examined ducks showed muscle emaciation (100%) either accompanied by congestion (34%) or paleness (66%). Slight congestion, either in the brain (82.5%) or intestine (75.25%), was predominantly detected. Based on molecular identification, the intestine had the highest percentage of positive detection (91.7%), followed by the skeletal muscle (70.8%), and the brain (20.8%). The main histopathological alterations were myofibre atrophy and degeneration, marked enteritis accompanied by lymphocytic infiltration in the lamina propria and submucosa, while the affected brains showed vasculitis, diffuse gliosis, and Purkinje cell degeneration in the cerebellum. Next-generation sequencing further confirmed the presence of a variant strain of goose parvovirus (vGPV) that is globally known as NGPV and closely related to Chinese NGPV isolates. Using immunohistochemistry, the NGPV antigen was positively detected in the muscle fibres, enterocytes, and Purkinje cells in the cerebellum. These findings provided proof of the involvement of virus replication in the locomotor disorders linked to NGPV infection in ducks.

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