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Article ; Online: Modulation of IRAK enzymes as a therapeutic strategy against SARS-CoV-2 induced cytokine storm.

Mahmoud, Ismail Sami / Jarrar, Yazun Bashir / Febrimarsa

2023 Volume 23, Issue 6, Page(s) 2909–2923

Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the current pandemic coronavirus disease 2019 (COVID-19). Dysregulated and excessive production of cytokines and chemokines, known as cytokine storm, is frequently seen in ... ...

Abstract	Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the current pandemic coronavirus disease 2019 (COVID-19). Dysregulated and excessive production of cytokines and chemokines, known as cytokine storm, is frequently seen in patients with severe COVID-19 disease and it can provoke a severe systematic inflammation in the patients. The IL-1R/TLRs/IRAKs signaling network is a key pathway in immune cells that plays a central role in regulating innate immunity and inflammatory responses via stimulating the expression and production of various proinflammatory molecules including cytokines. Modulation of IRAKs activity has been proposed to be a promising strategy in the treatment of inflammatory disorders. In this review, we highlight the biochemical properties of IRAKs and their role in regulating inflammatory molecular signaling pathways and discuss the potential targeting of IRAKs to suppress the SARS-CoV-2-induced cytokine storm in COVID-19 patients.
MeSH term(s)	Humans ; COVID-19 ; Cytokine Release Syndrome/drug therapy ; Cytokines ; Immunity, Innate ; SARS-CoV-2
Chemical Substances	Cytokines
Language	English
Publishing date	2023-04-15
Publishing country	Italy
Document type	Journal Article ; Review
ZDB-ID	2053018-3
ISSN	1591-9528 ; 1591-8890
ISSN (online)	1591-9528
ISSN	1591-8890
DOI	10.1007/s10238-023-01064-7
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Article ; Online: Targeting the intestinal TMPRSS2 protease to prevent SARS-CoV-2 entry into enterocytes-prospects and challenges.

Mahmoud, Ismail Sami / Jarrar, Yazun Bashir

Molecular biology reports

2021 Volume 48, Issue 5, Page(s) 4667–4675

Abstract: The transmembrane protease serine 2 (TMPRSS2) is a membrane anchored protease that primarily expressed by epithelial cells of respiratory and gastrointestinal systems and has been linked to multiple pathological processes in humans including tumor growth, ...

Abstract	The transmembrane protease serine 2 (TMPRSS2) is a membrane anchored protease that primarily expressed by epithelial cells of respiratory and gastrointestinal systems and has been linked to multiple pathological processes in humans including tumor growth, metastasis and viral infections. Recent studies have shown that TMPRSS2 expressed on cell surface of host cells could play a crucial role in activation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein which facilitates the rapid early entry of the virus into host cells. In addition, direct suppression of TMPRSS2 using small drug inhibitors has been demonstrated to be effective in decreasing SARS-CoV-2 infection in vitro, which presents TMPRSS2 protease as a potential therapeutic strategy for SARS-CoV-2 infection. Recently, SARS-CoV-2 has been shown to be capable of infecting gastrointestinal enterocytes and to provoke gastrointestinal disorders in patients with COVID-19 disease, which is considered as a new transmission route and target organ of SARS-CoV-2. In this review, we highlight the biochemical properties of TMPRSS2 protease and discuss the potential targeting of TMPRSS2 by inhibitors to prevent the SARS-CoV-2 spreading through gastro-intestinal tract system as well as the hurdles that need to be overcome.
MeSH term(s)	Antiviral Agents/pharmacology ; COVID-19/metabolism ; Drug Evaluation, Preclinical ; Enterocytes/drug effects ; Enterocytes/metabolism ; Enterocytes/virology ; Humans ; SARS-CoV-2/drug effects ; SARS-CoV-2/physiology ; Serine Endopeptidases/metabolism ; Serine Proteinase Inhibitors/pharmacology ; Small Molecule Libraries/pharmacology ; Spike Glycoprotein, Coronavirus/metabolism ; Virus Internalization/drug effects ; COVID-19 Drug Treatment
Chemical Substances	Antiviral Agents ; Serine Proteinase Inhibitors ; Small Molecule Libraries ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2 ; Serine Endopeptidases (EC 3.4.21.-) ; TMPRSS2 protein, human (EC 3.4.21.-)
Language	English
Publishing date	2021-05-22
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	186544-4
ISSN	1573-4978 ; 0301-4851
ISSN (online)	1573-4978
ISSN	0301-4851
DOI	10.1007/s11033-021-06390-1
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Article ; Online: SARS-CoV-2 entry in host cells-multiple targets for treatment and prevention.

Mahmoud, Ismail Sami / Jarrar, Yazun Bashir / Alshaer, Walhan / Ismail, Said

Biochimie

2020 Volume 175, Page(s) 93–98

Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new viral disease that has gained global attention owing to its ability to provoke community and health-care-associated outbreaks of severe infections in human populations. The virus poses ...

Abstract	Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new viral disease that has gained global attention owing to its ability to provoke community and health-care-associated outbreaks of severe infections in human populations. The virus poses serious challenges to clinical management because there are still no approved anti- SARS-CoV-2 drugs available. In this mini-review, we summarize the much updated published reports that demonstrate the mechanism of SARS-CoV-2 entry into host cells, and discuss the availability and development of attractive host-based therapeutic options for SARS-CoV-2 infections.
MeSH term(s)	Betacoronavirus/metabolism ; Betacoronavirus/pathogenicity ; COVID-19 ; Coronavirus Infections/metabolism ; Coronavirus Infections/therapy ; Host-Pathogen Interactions/physiology ; Humans ; Pandemics ; Pneumonia, Viral/metabolism ; Pneumonia, Viral/therapy ; SARS-CoV-2 ; Virus Internalization
Keywords	covid19
Language	English
Publishing date	2020-05-29
Publishing country	France
Document type	Journal Article ; Review
ZDB-ID	120345-9
ISSN	1638-6183 ; 0300-9084
ISSN (online)	1638-6183
ISSN	0300-9084
DOI	10.1016/j.biochi.2020.05.012
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Article ; Online: SARS-CoV-2 entry in host cells-multiple targets for treatment and prevention

Mahmoud, Ismail Sami / Jarrar, Yazun Bashir / Alshaer, Walhan / Ismail, Said

Biochimie

2020 Volume 175, Page(s) 93–98

Keywords	Biochemistry ; General Medicine ; covid19
Language	English
Publisher	Elsevier BV
Publishing country	us
Document type	Article ; Online
ZDB-ID	120345-9
ISSN	0300-9084
ISSN	0300-9084
DOI	10.1016/j.biochi.2020.05.012
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Article ; Online: Systemic Sarcoidosis with Psoriasiform Plaques and Patchy Nonscarring Alopecia.

Omar, Shaimaa Ismail / Genedy, Rasha Mahmoud / Zaid, Sami Abdelhamid Abo

Advances in skin & wound care

2021 Volume 34, Issue 8, Page(s) 1–4

Abstract: Abstract: Cutaneous sarcoidosis occurs in about one-quarter of patients with systemic disease and presents with either specific or nonspecific signs. Psoriasiform sarcoidosis is an uncommon presentation. Herein, study authors report a rare case of ... ...

Abstract	Abstract: Cutaneous sarcoidosis occurs in about one-quarter of patients with systemic disease and presents with either specific or nonspecific signs. Psoriasiform sarcoidosis is an uncommon presentation. Herein, study authors report a rare case of systemic sarcoidosis that presented with psoriasiform plaques and patchy alopecia. The main patient complaint was disfigurement from skin lesions over different areas of his body, followed by scalp alopecia and uveitis. These lesions were well-defined plaques, some oozing and others scaly. Dermoscopic examination revealed yellow-orange globular structure. A biopsy was taken; the eventual diagnosis was sarcoidosis, for which the patient received treatment with systemic steroids, resulting in improvement of all of his lesions. Physicians should suspect sarcoidosis in any patient presenting with psoriasiform skin lesions not responding to traditional psoriasis treatment.
MeSH term(s)	Adult ; Alopecia/classification ; Alopecia/diagnosis ; Alopecia/physiopathology ; Egypt ; Humans ; Male ; Psoriasis/diagnosis ; Psoriasis/physiopathology ; Sarcoidosis/classification ; Sarcoidosis/diagnosis
Language	English
Publishing date	2021-07-14
Publishing country	United States
Document type	Case Reports ; Journal Article
ZDB-ID	2012792-3
ISSN	1538-8654 ; 1527-7941
ISSN (online)	1538-8654
ISSN	1527-7941
DOI	10.1097/01.ASW.0000755940.44258.ab
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Article ; Online: The association between smartphone use and sleep quality, psychological distress, and loneliness among health care students and workers in Saudi Arabia.

Alzhrani, Abdullah Muhammad / Aboalshamat, Khalid Talal / Badawoud, Amal Mohammmad / Abdouh, Ismail Mahmoud / Badri, Hatim Matooq / Quronfulah, Baraa Sami / Mahmoud, Mahmoud Abdulrahman / Rajeh, Mona Talal

PloS one

2023 Volume 18, Issue 1, Page(s) e0280681

Abstract: Background: The use of smartphones among the general public and health care practitioners, in particular, is ubiquitous. The aim of this study was to investigate the relationship between smartphone addiction and sleep quality, psychological distress, ... ...

Abstract	Background: The use of smartphones among the general public and health care practitioners, in particular, is ubiquitous. The aim of this study was to investigate the relationship between smartphone addiction and sleep quality, psychological distress, and loneliness among health care students and workers in Saudi Arabia. Methods: This cross-sectional study used an online questionnaire to collect data on smartphone addiction, sleep quality, psychological distress, and loneliness as well as demographic information. Results: A total of 773 health care students and workers participated in the study, with an average age of 25.95 ± 8.35, and 59.6% female participants. The study found a positive significant association between smartphone addiction and psychological distress (F(1,771) = 140.8, P < 0.001) and emotional loneliness (F(1,771) = 26.70, P < 0.001). Additionally, a significant negative association between smartphone addiction and sleep quality was found (F(1,771) = 4.208, P = 0.041). However, there was no significant relationship between smartphone addiction and social loneliness (F (1,771) = 0.544, P < 0.461). Conclusion: These findings suggest that smartphone addiction has a negative impact on psychological distress, sleep quality, and emotional loneliness among health care students and workers. It is important to promote strategies to reduce smartphone dependency in order to avoid the harmful consequences of smartphone addiction.
MeSH term(s)	Humans ; Female ; Male ; Smartphone ; Sleep Quality ; Loneliness/psychology ; Saudi Arabia/epidemiology ; Cross-Sectional Studies ; Behavior, Addictive/psychology ; Students/psychology ; Psychological Distress
Language	English
Publishing date	2023-01-26
Publishing country	United States
Document type	Journal Article
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0280681
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Targeting the intestinal TMPRSS2 protease to prevent SARS-CoV-2 entry into enterocytes-prospects and challenges

Mahmoud, Ismail Sami / Jarrar, Yazun Bashir

Molecular biology reports. 2021 May, v. 48, no. 5

2021

Abstract	The transmembrane protease serine 2 (TMPRSS2) is a membrane anchored protease that primarily expressed by epithelial cells of respiratory and gastrointestinal systems and has been linked to multiple pathological processes in humans including tumor growth, metastasis and viral infections. Recent studies have shown that TMPRSS2 expressed on cell surface of host cells could play a crucial role in activation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein which facilitates the rapid early entry of the virus into host cells. In addition, direct suppression of TMPRSS2 using small drug inhibitors has been demonstrated to be effective in decreasing SARS-CoV-2 infection in vitro, which presents TMPRSS2 protease as a potential therapeutic strategy for SARS-CoV-2 infection. Recently, SARS-CoV-2 has been shown to be capable of infecting gastrointestinal enterocytes and to provoke gastrointestinal disorders in patients with COVID-19 disease, which is considered as a new transmission route and target organ of SARS-CoV-2. In this review, we highlight the biochemical properties of TMPRSS2 protease and discuss the potential targeting of TMPRSS2 by inhibitors to prevent the SARS-CoV-2 spreading through gastro-intestinal tract system as well as the hurdles that need to be overcome.
Keywords	COVID-19 infection ; Severe acute respiratory syndrome coronavirus 2 ; digestive tract ; drugs ; enterocytes ; metastasis ; molecular biology ; neoplasms ; proteinases ; serine ; therapeutics ; viruses
Language	English
Dates of publication	2021-05
Size	p. 4667-4675.
Publishing place	Springer Netherlands
Document type	Article
Note	Review
ZDB-ID	186544-4
ISSN	1573-4978 ; 0301-4851
ISSN (online)	1573-4978
ISSN	0301-4851
DOI	10.1007/s11033-021-06390-1
Database	NAL-Catalogue (AGRICOLA)

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Article: Effect of COVID-19 Pandemic on Neonatal Sepsis.

Mahmoud, Ahmed M / Alpakistany, Tariq A / Ismail, Khadiga A / Hawash, Yousry A / Jaafar, Najwa / Mohamed, Medhat M / Sami, Rokayya / Khalifa, Osama M

Clinical laboratory

2022 Volume 68, Issue 5

Abstract: Background: There is a sudden rise in infectious diseases, with special concern to the most recent SARS-CoV 2 outbreak. A retrospective study was conducted to study the effect of this outbreak on neonatal sepsis as a global issue that poses a challenge ... ...

Abstract	Background: There is a sudden rise in infectious diseases, with special concern to the most recent SARS-CoV 2 outbreak. A retrospective study was conducted to study the effect of this outbreak on neonatal sepsis as a global issue that poses a challenge for pediatric management and to identify its risk factors, microbial profile, and mortality rate at King Faisal Medical Complex, Taif, KSA, a COVID-19-tertiary care segregation hospital. Methods: This research included 111 neonates with a culture-proven diagnosis of neonatal sepsis (4 and 62 cases during 2019 and 2020, respectively). Results: During 2019 early onset sepsis (EOS) occurred in 6/49 (12.2%) while in 2020 22/62 (35.5%), and during 2019 late onset sepsis (LOS) occurred in 43/49 (87.7%) while in 2020 40/62 (64.5%). Premature rupture of membrane was the major neonatal risk factor for EOS during 2019 and 2020 with proportions of 4 (66.7%), 20 (90.9%); respectively. As regards LOS, the peripherally inserted central catheters and peripheral lines were the top neonatal risk factors. In the two-year outbreak, the most prevalent causative organism for EOS neonates was Escherichia coli and for LOS neonates it was Klebsiella. There was non-significant change in the mortality rate of neonatal sepsis between 2019 and 2020. However, the mortality rate was higher in EOS 9/22 (40.9%) in 2020 in comparison to 2/6 (33.3%) in 2019. Conclusions: Neonatal sepsis remains a major health problem causing serious morbidity and mortality, and health care policy makers have to implement EOS preventive measures.
MeSH term(s)	COVID-19/epidemiology ; Child ; Escherichia coli ; Humans ; Infant, Newborn ; Intensive Care Units, Neonatal ; Neonatal Sepsis/diagnosis ; Neonatal Sepsis/epidemiology ; Pandemics ; Retrospective Studies ; Sepsis/diagnosis ; Sepsis/epidemiology
Language	English
Publishing date	2022-05-10
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1307629-2
ISSN	1433-6510 ; 0941-2131
ISSN	1433-6510 ; 0941-2131
DOI	10.7754/Clin.Lab.2021.210711
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Article ; Online: Early-Onset Colorectal Cancer in Egypt: Pathological Characters, Patterns of Care, and Survival Compared to Average-Age Onset Colorectal Cancer: A Retrospective Multicenter Study.

Rashad, Noha / Eid Salem, Salem / Meheissen, Mohamed A M / Refaat, Ghada / Mahmoud Sami, Heba / Temerik, Abdelsalam / Kordy, Nashwa / Daniel, Mina A / El-Kaffas, Mohamed / Esam, Mohamed / El Mansy, Hazem / Elkerm, Yasser / Abdelaziz Elsaid, Amr / Attia Ismail, Abdelsalam / Saber Abdelhalim, Mohyeldin / Moustafa Ahmad, Lamiaa / Akram Mahmoud, Mai / El Desouky, Eman D

JCO global oncology

2024 Volume 10, Page(s) e2300372

Abstract: Purpose: Early-onset colorectal cancer (EOCRC) is a rising health problem. The incidence of EOCRC has increased over the past 2 decades all over the world. Reports from Egypt since the 1990s have reported a higher incidence among young populations with ... ...

Abstract	Purpose: Early-onset colorectal cancer (EOCRC) is a rising health problem. The incidence of EOCRC has increased over the past 2 decades all over the world. Reports from Egypt since the 1990s have reported a higher incidence among young populations with no identifiable risk factors. The aim of this study was to assess EOCRC in Egypt regarding incidence, characteristics, treatment pattern, and survival compared with average age onset and elderly patients. Materials and methods: This was a retrospective, record-based, cohort study combining data from four different cancer centers in Egypt. We grouped patients according to age into three categories: the EOCRC group for patients age ≤45 years and the average age onset and elderly cancer group (for patients age ≥65 years). Results: The study included 1,310 patients with histopathologically proven colorectal cancer, representing four different geographical areas in Egypt. Patients with EOCRC represented 42.4% of the study population. Female patients were 50.6% among the EOCRC group and 52.5% among the average age group. Rectal tumors were significantly higher in EOCRC (54.7% Conclusion: A comprehensive framework for the study of EOCRC is required in Egypt as well as a genomic analysis to identify possible underlying genetic alterations responsible for the high incidence of EOCRC.
MeSH term(s)	Aged ; Humans ; Female ; Middle Aged ; Cohort Studies ; Egypt/epidemiology ; Retrospective Studies ; Disease-Free Survival ; Colorectal Neoplasms/epidemiology ; Colorectal Neoplasms/therapy
Language	English
Publishing date	2024-03-29
Publishing country	United States
Document type	Multicenter Study ; Journal Article
ISSN	2687-8941
ISSN (online)	2687-8941
DOI	10.1200/GO.23.00372
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: 1,4-Naphthoquinone Induces FcRn Protein Expression and Albumin Recycling in Human THP-1 Cells.

Esawi, Ezaldeen Ismael / Mahmoud, Ismail Sami / Abdullah, Mohammad Salah / Abuarqoub, Duaa Azmi / Ahram, Mamoun Ahmad / Alshaer, Walhan Mohammad

ACS omega

2023 Volume 8, Issue 18, Page(s) 16491–16499

Abstract: The neonatal Fc receptor (FcRn) has been established as a major factor in regulating the metabolism of albumin and IgG in humans by protecting them from intracellular degradation after they are endocytosed into cells. We assume that increasing the levels ...

Abstract	The neonatal Fc receptor (FcRn) has been established as a major factor in regulating the metabolism of albumin and IgG in humans by protecting them from intracellular degradation after they are endocytosed into cells. We assume that increasing the levels of endogenous FcRn proteins in cells would be beneficial to enhance the recycling of these molecules. In this study, we identify the compound 1,4-naphthoquinone as an efficient stimulator of FcRn protein expression in human THP-1 monocytic cells with potency at the submicromolar range. Also, the compound increased the subcellular localization of FcRn to the endocytic recycling compartment and enhanced human serum albumin recycling in the PMA-induced THP-1 cells. These results suggest that 1,4-naphthoquinone stimulates FcRn expression and activity in human monocytic cells
Language	English
Publishing date	2023-04-25
Publishing country	United States
Document type	Journal Article
ISSN	2470-1343
ISSN (online)	2470-1343
DOI	10.1021/acsomega.3c01678
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