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1. Unveiling the interplay between NSAID-induced dysbiosis and autoimmune liver disease in children: insights into the hidden gateway to autism spectrum disorders. Evidence from ex vivo, in vivo, and clinical studies

Author

Mohamed, Doaa I., primary, Abo Nahas, Hebatallah H., additional, Elshaer, Asmaa M., additional, El-Waseef, Dalia Alaa El-Din Aly, additional, El-Kharashi, Omnyah A., additional, Mohamed, Soha M. Y., additional, Sabry, Yasmine Gamal, additional, Almaimani, Riyad A., additional, Almasmoum, Hussain A., additional, Altamimi, Abdulmalik S., additional, Ibrahim, Ibrahim Abdel Aziz, additional, Alshawwa, Samar Z., additional, Jaremko, Mariusz, additional, Emwas, Abdul-Hamid, additional, and Saied, Essa M., additional

Published
2023
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2. Unveiling the interplay between NSAID-induced dysbiosis and autoimmune liver disease in children: insights into the hidden gateway to autism spectrum disorders. Evidence from ex vivo, in vivo, and clinical studies

Author

Mohamed, Doaa I., Abo Nahas, Hebatallah H., Elshaer, Asmaa, Alaa El-Din Aly El-Waseef, Dalia, El-Kharashi, Omnyah A., Mohamed, Soha M. Y., Sabry, Yasmine Gamal, Almaimani, Riyad, Almasmoum, Hussain, Altamimi, Abdulmalik S., Ibrahim, Ibrahim Abdel Aziz, Alshawwa, Samar, Jaremko, Mariusz, Emwas, Abdul-Hamid, M. Saied, Essa, Mohamed, Doaa I., Abo Nahas, Hebatallah H., Elshaer, Asmaa, Alaa El-Din Aly El-Waseef, Dalia, El-Kharashi, Omnyah A., Mohamed, Soha M. Y., Sabry, Yasmine Gamal, Almaimani, Riyad, Almasmoum, Hussain, Altamimi, Abdulmalik S., Ibrahim, Ibrahim Abdel Aziz, Alshawwa, Samar, Jaremko, Mariusz, Emwas, Abdul-Hamid, and M. Saied, Essa

Abstract

Autism spectrum disorders (ASD) represent a diverse group of neuropsychiatric conditions, and recent evidence has suggested a connection between ASD and microbial dysbiosis. Immune and gastrointestinal dysfunction are associated with dysbiosis, and there are indications that modulating the microbiota could improve ASD-related behaviors. Additionally, recent findings highlighted the significant impact of microbiota on the development of autoimmune liver diseases, and the occurrence of autoimmune liver disease in children with ASD is noteworthy. In the present study, we conducted both an in vivo study and a clinical study to explore the relationship between indomethacin-induced dysbiosis, autoimmune hepatitis (AIH), and the development of ASD. Our results revealed that indomethacin administration induced intestinal dysbiosis and bacterial translocation, confirmed by microbiological analysis showing positive bacterial translocation in blood cultures. Furthermore, indomethacin administration led to disturbed intestinal permeability, evidenced by the activation of the NLRP3 inflammasomes pathway and elevation of downstream biomarkers (TLR4, IL18, caspase 1). The histological analysis supported these findings, showing widened intestinal tight junctions, decreased mucosal thickness, inflammatory cell infiltrates, and collagen deposition. Additionally, the disturbance of intestinal permeability was associated with immune activation in liver tissue and the development of AIH, as indicated by altered liver function, elevated ASMA and ANA in serum, and histological markers of autoimmune hepatitis. These results indicate that NSAID-induced intestinal dysbiosis and AIH are robust triggers for ASD existence. These findings were further confirmed by conducting a clinical study that involved children with ASD, autoimmune hepatitis (AIH), and a history of NSAID intake. Children exposed to NSAIDs in early life and complicated by dysbiosis and AIH exhibited elevated serum levels of NL, Peer Reviewed

Published
2023

4. Age and frailty are independently associated with increased covid-19 mortality and increased care needs in survivors: results of an international multi-centre study

Author

Alsahab, Mustafa, Beishon, Lucy, Brown, Bryony, Burn, Elinor, Burton, Jenni K, Cox, Natalie, Dani, Melanie, Elhadi, Muhammed, Freshwater, Sarah, Gaunt, Victoria, Gordon, Adam, Goujon, Marie, Hale, Matthew, Hughes, Terry, Jackson, Thomas A, Jelley, Benjamin, Khan, Asma, Khiroya, Heena, Lal, Rajni, Madden, Katy, Magill, Laura, Masoli, Jane, Masud, Tahir, McCluskey, Lauren, McNeela, Natalie, Mohammedseid-Nurhussien, Awolkhier, Moorey, Hannah, Lochlainn, Mary Ni, Nirantharakumar, Krishnarajah, Okoth, Kelvin, Osuafor, Christopher N, Patterson, Katherine, Pearson, Grace M E, Perry, Rita, Pettitt, Michala, Pigott, Jennifer, Pinkney, Thomas, Quinn, Terence, Reynolds, Abigail, Richardson, Sarah, Sanyal, Nik, Seed, Adam, Sleeman, Isobel, Soo, Chee, Steves, Claire, Strain, W David, Taylor, Joanne, Torsney, Kelli, Welch, Carly, Wilson, Daisy, Witham, Miles, Elazeem, Hossam Aldein S Abd, Abdelhafez, Mohammed H, Abdelmalak, Amir, Abdelwahab, Omar A, Abdulhadi, Osama M A S, Adewole, Olubayode, Ahmad, Mohammed, Ahmed, Eltayeb A, Ahmed, Hazem, Ahmed, Islam A, Akcay, Mertcan, Akdeniz, Yeşim, Akın, Emrah, Akladious, Carolyn, Alessandri, Francesco, Ali, Ali, Aljafari, Abdulmalek, Aljafari, Abdulmoiz, Al-Sadawi, Mohammed, Al-Sodani, Lobna, Altintoprak, Fatih, Amaratungaz, Gitanjali, Amer, Jocelyn, Amini, Sylvia, Amir, Taha, Anandarajah, Cheran, Anders, Rachael, Ansari, Muhammed H, Appiah, Kingsley, Atia, Jolene, Atkin, Catherine, Aujayeb, Avinash, Awad, Elsayed M, Azab, Mohammed A, Azam, Mohammad T, Aziz, Sally, Azzam, Ahmed Y, Babar, Laxmi, Babb, Laura, Badh, Manpreet, Baguneid, Clare, Bailey, Emily, Baili, Efstratia, Baldwin, Sarah, Baloyiannis, Ioannis, Bannerjee, Moulinath, Barnard, Anna, Barra, Fabio, Bashir, Hannah, Bawor, Monica, Bayhan, Zülfü, Belcher, James, Belgamwar, Ravindra, Bentley, Corrina, Birchenough, Amy, Bo, Yen Nee J, Boden, Hayley R, Bouhuwaish, Ahmad, Brachini, Gioia, Bremner, Laura, Bridgwater, Hannah, Bryant, Catherine, Budd, Gabrielle, Budd, Sharon, Budzikoski, Adam, Bulla, Reem, Buondonno, Antonio, Burden, Nicole, Butt, Hejab, Capoglu, Recayi, Caracostea, Andra, Cardoso, Rifa, Carr, Alexis, Carrasco-Prats, Milagros, Cattel, Caterina, Ceccarelli, Giancarlo, Cecere, Giuseppe, Charalabopoulos, Alexandros, Charsley, Evelyn, Cheney-Lowe, Hannah, Chevallier, Theodore, Choudhry, Asad J, Ciccarone, Flavia, Cicerchia, Pierfranco M, Cirillo, Bruno, Collins, Fatma D, Comerford, Victoria, Cordie, Ahmed, Coulter, Siobhan, Coulthard, Nick, Cox, Catrin, Cox, Victoria, Crowe, Andrew, Cullen, Jack, Cummings, Jean, Cunningham, Niamh, Curley, Daniel, Currie, Hannah, Daly, Madeleine, Darley, Jay, Dattani, Nikhita, Davakis, Spyridon, Davies, Rowan, De Paola, Gilda, De Toma, Giorgio, Del Valle-Ruiz, Sergio, Deldar, Benyamin, Demir, Hakan, Desai, Arjun, Desai, Nirali, Devaney, Alice, Dew, Lindsey, Dhesi, Jugdeep, Dias, Maria, Dick, Gordon, Doddamani, Parveen, Dogra, Gurinder, Doll, Tina, Dooley, Hannah C, Dost, Samiullah, Dotchin, Catherine, Dowell, Hannah, Draghita, Ioan M, Dundas, James M, Duranti, Giulia, Dusara, Hiren, Dwivedi, Rajesh, Dyer, Adam H, Eastaugh, Alison, Edwards, Elinor, Elghazaly, Shrouk M, Elmehrath, Ahmed O, Elrick, Hope, El-Shazly, Mostafa, Emery, Alexander, Etchill, Eric W, Evans, Sarah, Evison, Felicity, Fairhead, Cassandra, Faulkner, Margherita, Felska, Agnieszka, Fernandez, Antia, Fernández-Fernández, Pedro V, Ferraiolo, Antonella, Ferrero, Simone, Fiori, Enrico, Firat, Necattin, Fisk, Gracie, Fleck, Anna, Fonsi, Giovanni B, Gabre-Kidan, Alodia, Gallo, Gaetano, Gandhi, Ratnam, Garner, Madeleine, Georgiou, Nikolaos, Gerretsen, Hannah, Ghannam, Nourhan A A, Ghobrial, Andrew, Ghobrial, Hedra, Ghufoor, Zaynub, Gibbon, Jake, Gilbert, Georgia F, Giles, Marie, Giménez-Francés, Clara, Gonullu, Emre, Gray, Amy, Gray, Joshua H, Green, Deirdre, Greene, Charlotte, Griffin, Ellanna, Griffith, Karla, Grubb, Anthony, Guan, Yue, Guerero, Daniel N, Gupta, Ayushi, Gustavino, Claudio, Guzman, Laurenny, Hadreiez, Ahmed K M, Hajiioannou, Jiannis, Hanji, Deevia, Madhavan, Deepthy Hari, Harmantepe, Tarık, Harrison, Patrick, Hart, Barbara, Haslam, Aidan, Haunton, Victoria, Haut, Elliott R, Heinsohn, Torben, Hennah, Lindsay, Hetta, Helal F, Hickman, Alexander, Hobill, Abigail, Hogan, Patrick C P, Hogan, Vesna, Holmes, Elizabeth, Honney, Katie, Hood, Katharine, Hopkinson, Katherine, Howells, Lara, Hrouda, Nicole, Hunsley, Danielle, Hurst, William, Hussein, Rand A, Ibrahim, Mohamed Eltaher A A, Ibtida, Ishmam, Ibukunoluwakitan, Aina, Ishlek, Irem, Iyer, Rishi, Jackson, Karl, Jackson, Rosie, James, Ellen, Jarvis, Hayley, Jeffs, Sophie, Jenko, Nathan, Jeyakumar, Sasha, Kabir, Shahriar, Kainth, Harjinder, Kalloo, Jason, Kanzaria, Akhil, Karapanou, Amalia, Kardaman, Nuha, Karthikeyan, Sandeep, Karunatilleke, Anne, Kelly, Mairead, Kelly, Nicola I, Khalid, Hesham, Khan, Haris, Khan, Muhammad S, King, Matthew, Kneen, Thomas, Kok, Li, Kratochwila, Chiara, Kuzeva, Aneliya, Lapolla, Pierfrancesco, Lau, Rebecca, Law, Kar Yee, Leadbetter, Aimee, Lee, Gabriel, Lee, Helena, Levinson, Gavriella, Lewis, Grace, Liakakos, Theodore, Lim, Stephen, Lis, Danielle, Livesey, Emma, López-Morales, Pedro, Lowes, Lily, Lunt, Eleanor, Lyon, Emily, Madan, Suvira, Majid, Zeinab, Malapati, Harsha, Man, Jade, Mandane, Baguiasri, Manning, Sarah H, Mantoglu, Baris, Martínez-Sanz, Nuria, Marx, William, Masood, Almontacer E B, Maughan, Tom, Mawhinney, Jamie, Maxfield, Dominic, Mayer, Jordan, Maynard, Henry, McDonald, Claire, McGovern, Aine, Mclachlan, Sophie, Medina-Manuel, Esther, Meneghini, Simona, Metcalf, Michelle, Millwood-Hargrave, John, Mingoli, Andrea, Miu, Kelvin, Mohamed, Fawsiya, Mohamed, Soha M, Hussein, Aliae A R Mohamed, Mohammad, Abdulkader, Mohammed, Aaliya, Momen, Ahmed A, Moomo, Farhana, Mora-Guzmán, Ismael, Moriarty, Lizzie, Morrin, Hamilton, Morris, Claire, Moss, Nicholas, Moustafa, Mohamed M, Mpoura, Maria, Mubin, Mohammed, Muhtaroglu, Ali, Muir, Georgina, Mulhern, Stephanie, Muller, Daniel, Murphy, Declan C, Muzammil, Bushra, Nadkarni, Varun, Nageh, Mariam Albatoul, NasrEldin, Yasmin K, Nawaz, Wasim, Nguyen, Hanna, Cheallaigh, Cliona Ni, Noar, Alexander, North, Samuel, Nwolu, Favour, O’Docherty, Alice, Odutola, Omoteniola, O’Dwyer, Sinead, Ogochukwu, Olebu, O’Mahony, Catherine, Orlando, Lia, Osterdahl, Marc, Page, Christina, Panayotidis, Ismini, Pancholi, Shivam, Parkin, Jessica, Passby, Lauren C, Pastor-Pérez, Patricia, Patel, Harnish, Patel, Shefali, Penfold, Rose, Perinpanathan, Rupini, Perivoliotis, Konstantinos, Perra, Teresa, Pinkney, Martha, Pinotti, Enrico, Porcu, Alberto, Price, Angeline, Pugliese, Francesco, Puri, Prabhleen, Pytraczyk, Sylvia, Qaiser, Yusra, Qurashi, Maria, Radenkovic, Dina, Rajeswaran, Thurkka, Rapaport, Sarah F, Razzak, Tahmina, Reilly, Lara, Reynolds, Paul, Richardson, Alexandra, Roberts, Amelia, Roberts-Rhodes, Charlotte, Robinson, Tanya, Rocca, Aldo, Ross-Skinner, Emily, Ruiz-Marín, Miguel, Ryall, Rebecca, Saad, Alshaimaa M, Saad, Mahmoud M, Sadiq, Ambreen, Sammarco, Giuseppe, Sampanis, Michail A, Sanghvi, Hazel, Sapienza, Paolo, Sayers, Ross, Scott, Luca, Sen, Michael, Shaban, Mosab A A, Shakespeare, Kathleen T, Shaw, Ellie, Shaw, Hannah, Sheldrake, Jonathan, Sim, Sing Yang, Simonelli, Luigi, Sipsas, Nikolaos V, Sivam, Jarita, Sivarajan, Sri, Smith, Jennifer, Speranza, Fabio, Spice, Claire, Stafford, Amanda, Stambollouian, Katharine, Stevens, Kent A, Stewart, Jack, Stratton, Emma, Street, Hannah, Surtees, Michael, Swinnerton, Emma, Taher, Ahmed S A, Tait, Caroline, Taylor, Amybel, Thake, Miriam, Thin, Katie, Thould, Hannah, Thyn, Thyn, To, Benjaman, Tobiss, Hannah, Toppley, Kathryn, Townsend, Liam, Tullo, Ellen, Tzovaras, George, Umeadi, Anthony, Vaidya, Hrisheekesh, Valero-Soriano, María, Varden, Rosanna, Vergani, Vittoria, Vervoort, Dominique, Vescio, Giuseppina, Vettasseri, Mark, Virk, Madiha, Vyas, Vaishali, Wagland, Joanne, Wallis, Stephanie, Warner, Chloe, Watkins, Eleanor, Watson, Hannah, Webb, Rachael, Welsh, Sarah H, West, Ruth, Whelan, Elisha, Whitney, Julie, Whitsey, Mark, Wilcock, Catherine, Wilkinson, Iain, Williams, David, Williamson, Megan, Willott, Ruth H, Wimalasundera, Mettha, Win, Yu Lelt, Winter, Laura, Worrall, Stephanie, Wright, Rebecca, Yeo, Natalie, Yeung, Eirene, Yigit, Merve, Yildiz, Yasin A, Yusuf, Humza, Zambon, Martina, Zaw, Hein, and Elabedeen, Omar Zein

Subjects
Male, Aging, medicine.medical_specialty, Frail Elderly, COVID-19, delirium, frailty, mortality, transitions of care, Cohort Studies, AcademicSubjects/MED00280, Interquartile range, Internal medicine, medicine, Dementia, Humans, Survivors, Aged, Proportional hazards model, business.industry, SARS-CoV-2, Hazard ratio, Odds ratio, General Medicine, medicine.disease, Confidence interval, frailty,COVID-19, Ageing, Delirium, Female, medicine.symptom, Geriatrics and Gerontology, business, Cohort study, Research Paper
Abstract

Introduction Increased mortality has been demonstrated in older adults with coronavirus disease 2019 (COVID-19), but the effect of frailty has been unclear. Methods This multi-centre cohort study involved patients aged 18 years and older hospitalised with COVID-19, using routinely collected data. We used Cox regression analysis to assess the impact of age, frailty and delirium on the risk of inpatient mortality, adjusting for sex, illness severity, inflammation and co-morbidities. We used ordinal logistic regression analysis to assess the impact of age, Clinical Frailty Scale (CFS) and delirium on risk of increased care requirements on discharge, adjusting for the same variables. Results Data from 5,711 patients from 55 hospitals in 12 countries were included (median age 74, interquartile range [IQR] 54–83; 55.2% male). The risk of death increased independently with increasing age (>80 versus 18–49: hazard ratio [HR] 3.57, confidence interval [CI] 2.54–5.02), frailty (CFS 8 versus 1–3: HR 3.03, CI 2.29–4.00) inflammation, renal disease, cardiovascular disease and cancer, but not delirium. Age, frailty (CFS 7 versus 1–3: odds ratio 7.00, CI 5.27–9.32), delirium, dementia and mental health diagnoses were all associated with increased risk of higher care needs on discharge. The likelihood of adverse outcomes increased across all grades of CFS from 4 to 9. Conclusion Age and frailty are independently associated with adverse outcomes in COVID-19. Risk of increased care needs was also increased in survivors of COVID-19 with frailty or older age.

Published
2021

7. Trimetazidine Alleviates Bleomycin-Induced Pulmonary Fibrosis by Targeting the Long Noncoding RNA CBR3-AS1-Mediated miRNA-29 and Resistin-Like Molecule alpha 1: Deciphering a Novel Trifecta Role of LncRNA CBR3-AS1/miRNA-29/FIZZ1 Axis in Lung Fibrosis.

Author

Alzahrani AR, Mohamed DI, Abo Nahas HH, Alaa El-Din Aly El-Waseef D, Altamimi AS, Youssef IH, Ibrahim IAA, Mohamed SMY, Sabry YG, Falemban AH, Elhawary NA, Bamagous GA, Jaremko M, and Saied EM

Subjects
Animals, Mice, Male, Mice, Inbred C57BL, Bleomycin, RNA, Long Noncoding genetics, RNA, Long Noncoding metabolism, MicroRNAs genetics, MicroRNAs metabolism, Pulmonary Fibrosis drug therapy, Pulmonary Fibrosis chemically induced, Pulmonary Fibrosis metabolism, Pulmonary Fibrosis pathology, Trimetazidine pharmacology
Abstract

Introduction: Pulmonary fibrosis (PF) and tissue remodeling can greatly impair pulmonary function and often lead to fatal outcomes., Methodology: In the present study, we explored a novel molecular interplay of long noncoding (Lnc) RNA CBR3-AS1/ miRNA-29/ FIZZ1 axis in moderating the inflammatory processes, immunological responses, and oxidative stress pathways in bleomycin (BLM)-induced lung fibrosis. Furthermore, we investigated the pharmacological potential of Trimetazidine (TMZ) in ameliorating lung fibrosis., Results: Our results revealed that the BLM-treated group exhibited a significant upregulation in the expression of epigenetic regulators, lncRNA CBR3-AS1 and FIZZ1, compared to the control group (P<0.0001), along with the downregulation of miRNA-29 expression. Furthermore, Correlation analysis showed a significant positive association between lnc CBR3-AS1 and FIZZ1 (R=0.7723, p<0.05) and a significant negative association between miRNA-29 and FIZZ1 (R=-0.7535, p<0.05), suggesting lnc CBR3-AS1 as an epigenetic regulator of FIZZ1 in lung fibrosis. BLM treatment significantly increased the expression of Notch, Jagged1, Smad3, TGFB1, and hydroxyproline. Interestingly, the administration of TMZ demonstrated the ability to attenuate the deterioration effects caused by BLM treatment, as indicated by biochemical and histological analyses. Our investigations revealed that the therapeutic potential of TMZ as an antifibrotic drug could be ascribed to its ability to directly target the epigenetic regulators lncRNA CBR3-AS1/ miRNA-29/ FIZZ1, which in turn resulted in the mitigation of lung fibrosis. Histological and immunohistochemical analyses further validated the potential antifibrotic effects of TMZ by mitigating the structural damage associated with fibrosis., Discussion: Taken together, our study showed for the first time the interplay between epigenetic lncRNAs CBR3-AS1 and miRNA-29 in lung fibrosis and demonstrated that FIZZ1 could be a downregulatory gene for lncRNA CBR3-AS1 and miRNA-29. Our key findings demonstrate that TMZ significantly reduces the expression of fibrotic, oxidative stress, immunomodulatory, and inflammatory markers, along with epigenetic regulators associated with lung fibrosis. This validates its potential as an effective antifibrotic agent by targeting the CBR3-AS1/miRNA-29/FIZZ1 axis., Competing Interests: The authors declare that this research was conducted in the absence of any commercial or financial relationships that could be construed as potential conflicts of interest., (© 2024 Alzahrani et al.)

Published
2024
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8. Serum Interleukin-33 in Behcet's Disease: Its Relation to Disease Activity and Clinical Manifestations.

Author

Fawzy RM, Said EA, Mohamed SM, Fouad NA, and Akl EM

Subjects
Adult, Arthritis, Rheumatoid blood, Case-Control Studies, Female, Humans, Male, Severity of Illness Index, Behcet Syndrome blood, Interleukin-33 blood
Abstract

Behcet's disease (BD) is a chronic systemic inflammatory disorder characterized by a ‎‎course of remissions and exacerbations of unpredictable frequency and duration‎. Pro-‎inflammatory cytokines seem to be responsible for the enhanced inflammatory ‎‎response in BD., Aim of the Work: This study aimed to investigate serum levels of IL-33 in patients with Behcet's disease (BD) and their relationship to disease activity and clinical manifestations. Thirty patients with BD were enrolled and subjected to assessment of disease activity according to Behcet's Disease Current Activity Form (BDCAF) score. Serum IL-33 levels were determined using Enzyme-Linked-Immunosorbent Assay (ELISA). Thirty age and sex matched rheumatoid arthritis patients and thirty healthy volunteers were included in this study as control groups. Serum IL-33 level was 132.5±19 pg\ml, 101.2±20.1 pg\ml and 31.5±10.5 pg\ml in RA, BD and healthy control groups respectively. IL-33 was significantly higher in BD patients (101.2±20.1pg/ml) as compared to healthy controls (31.5±10.5 pg/ml) but lower than rheumatoid arthritis patients (132.5±19.1 pg/ml). Levels of IL-33 were significantly increased in BD patients with skin lesions (Erythema nodosum & Acneiform lesions) and ocular lesions (retinal vasculitis) (P<0.05), and a positive correlation was found between BDCAF score and IL-33serum levels (r=0.9, P<0.001). In conclusions, serum IL-33 level is elevated in active BD patients with skin and ocular affection and correlates with disease activity., (Copyright© by the Egyptian Association of Immunologists.)

Published
2015

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