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Article ; Online: Potent virucidal activity of honeybee "Apis mellifera" venom against Hepatitis C Virus.

Sarhan, Moustafa / El-Bitar, Alaa M H / Hotta, Hak

Toxicon : official journal of the International Society on Toxinology

2020 Volume 188, Page(s) 55–64

Abstract: Hepatitis C virus (HCV) is a global viral widespread without an available vaccine to prevent ...

Abstract	Hepatitis C virus (HCV) is a global viral widespread without an available vaccine to prevent infection. HCV infection can cause serious liver diseases such as hepatocellular carcinoma (HCC). Current treatment of HCV infection depends on the FDA approved direct-acting antivirals (DAAs) which have side effects and expensive. Thus, development of a novel, more efficient, along with affordable pricing anti-HCV agents is still required. The purpose of the present study is to evaluate the antiviral effects of bee venom (BV) from the honeybee Apis mellifera on the HCV replication life cycle. The crude venom and its components were examined for their anti-HCV activities using Huh7it-1 cultured cells and the JFH1 strain of HCV genotype 2a. Results revealed that BV inhibited HCV infection with 50% inhibitory concentration (IC
MeSH term(s)	Animals ; Antiviral Agents/pharmacology ; Bee Venoms/pharmacology ; Bees ; Carcinoma, Hepatocellular ; Cell Line ; Hepacivirus ; Hepatitis C ; Hepatitis C, Chronic ; Liver Neoplasms ; Melitten ; Peptides
Chemical Substances	Antiviral Agents ; Bee Venoms ; Peptides ; Melitten (20449-79-0) ; mast cell degranulating peptide (32908-73-9)
Language	English
Publishing date	2020-10-14
Publishing country	England
Document type	Journal Article
ZDB-ID	204479-1
ISSN	1879-3150 ; 0041-0101
ISSN (online)	1879-3150
ISSN	0041-0101
DOI	10.1016/j.toxicon.2020.10.014
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Article ; Online: Virocidal activity of Egyptian scorpion venoms against hepatitis C virus.

El-Bitar, Alaa M H / Sarhan, Moustafa M H / Aoki, Chie / Takahara, Yusuke / Komoto, Mari / Deng, Lin / Moustafa, Mohsen A / Hotta, Hak

Virology journal

2015 Volume 12, Page(s) 47

Abstract: Background: Hepatitis C virus (HCV) is a major global health problem, causing chronic hepatitis ...

Abstract	Background: Hepatitis C virus (HCV) is a major global health problem, causing chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. Development of well-tolerated regimens with high cure rates and fewer side effects is still much needed. Recently, natural antimicrobial peptides (AMPs) are attracting more attention as biological compounds and can be a good template to develop therapeutic agents, including antiviral agents against a variety of viruses. Various AMPs have been characterized from the venom of different venomous animals including scorpions. Methods: The possible antiviral activities of crude venoms obtained from five Egyptian scorpion species (Leiurus quinquestriatus, Androctonus amoreuxi, A. australis, A. bicolor and Scorpio maurus palmatus) were evaluated by a cell culture method using Huh7.5 cells and the J6/JFH1-P47 strain of HCV. Time-of-addition experiments and inactivation of enzymatic activities of the venoms were carried out to determine the characteristics of the anti-HCV activities. Results: S. maurus palmatus and A. australis venoms showed anti-HCV activities, with 50% inhibitory concentrations (IC₅₀) being 6.3 ± 1.6 and 88.3 ± 5.8 μg/ml, respectively. S. maurus palmatus venom (30 μg/ml) impaired HCV infectivity in culture medium, but not inside the cells, through virocidal effect. The anti-HCV activity of this venom was not inhibited by a metalloprotease inhibitor or heating at 60°C. The antiviral activity was directed preferentially against HCV. Conclusions: S. maurus palmatus venom is considered as a good natural source for characterization and development of novel anti-HCV agents targeting the entry step. To our knowledge, this is the first report describing antiviral activities of Egyptian scorpion venoms against HCV, and may open a new approach towards discovering antiviral compounds derived from scorpion venoms.
MeSH term(s)	Animals ; Antiviral Agents/toxicity ; Hepacivirus/drug effects ; Hepacivirus/physiology ; Hepatitis C/virology ; Humans ; Scorpion Venoms/toxicity ; Scorpions/chemistry
Chemical Substances	Antiviral Agents ; Scorpion Venoms
Keywords	covid19
Language	English
Publishing date	2015-03-24
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1743-422X
ISSN (online)	1743-422X
DOI	10.1186/s12985-015-0276-6
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Article ; Online: Virucidal activity of oriental hornet Vespa orientalis venom against hepatitis C virus

Moustafa Sarhan / Alaa M. H. El-Bitar / Amaal Mohammadein / Mohammed Elshehaby / Hak Hotta

Journal of Venomous Animals and Toxins including Tropical Diseases, Vol

2021 Volume 27

Abstract: Abstract Background Hepatitis C virus (HCV) infection is a major worldwide health problem ...

Abstract	Abstract Background Hepatitis C virus (HCV) infection is a major worldwide health problem that can cause liver fibrosis and hepatocellular carcinoma (HCC). The clinical treatment of HCV infection mainly relies on the use of direct-acting antivirals (DAAs) that are usually expensive and have side effects. Therefore, achieving the discovery of more successful agents is always urgent. In this context, antiviral compounds that inhibit viral infections and disease progression with important therapeutic activities have been identified in animal venoms including arthropod toxins. This indicates that arthropod venoms represent a good natural source of promising candidates for new antivirals. Methods The antiviral activity of the wasp venom (WV), isolated from the Oriental hornet (Vespa orientalis), was assessed using cell culture technique with human hepatocellular carcinoma-derived cell line (Huh7it-1) and the recombinant strain of HCV genotype 2a (JFH1). Results The results revealed that WV inhibited HCV infectivity with 50% inhibitory concentration (IC50) of 10 ng/mL, while the 50% cytotoxic concentration (CC50) was 11,000 ng/mL. Time of addition experiment showed that the WV blocked HCV attachment/entry to the cells probably through virucidal effect. On the other hand, the venom showed no inhibitory effect on HCV replication. Conclusion WV can inhibit the entry stage of HCV infection at non-cytotoxic concentrations. Therefore, it could be considered a potential candidate for characterization of natural anti-HCV agents targeting the entry step.
Keywords	Wasp venom ; Vespa orientalis ; Hepatitis C virus (HCV) ; Antiviral activity ; Arctic medicine. Tropical medicine ; RC955-962 ; Toxicology. Poisons ; RA1190-1270 ; Zoology ; QL1-991
Subject code	570
Language	English
Publishing date	2021-11-01T00:00:00Z
Publisher	SciELO
Document type	Article ; Online
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Article ; Online: CCAAT/enhancer binding protein delta (C/EBPδ) demonstrates a dichotomous role in tumour initiation and promotion of epithelial carcinoma.

Sowamber, Ramlogan / Chehade, Rania / Bitar, Mahmoud / Dodds, Leah V / Milea, Anca / Slomovitz, Brian / Shaw, Patricia A / George, Sophia H L

EBioMedicine

2019 Volume 44, Page(s) 261–274

Abstract: Background: CCAAT/enhancer binding protein delta (C/EBPδ,CEBPD), a gene part of the highly ... grade serous carcinomas of the ovary (HGSC). Overexpression of C/EBPδ in different tumours ... in normal tissue until activated by cytotoxic stressors.: Methods: Higher overall expression of C/EBPδ ...

Abstract	Background: CCAAT/enhancer binding protein delta (C/EBPδ,CEBPD), a gene part of the highly conserved basic-leucine zipper (b-ZIP) domain of transcriptional factors, is downregulated in 65% of high grade serous carcinomas of the ovary (HGSC). Overexpression of C/EBPδ in different tumours, such as glioblastoma and breast cancer either promotes tumour progression or inhibits growth and has low expression in normal tissue until activated by cytotoxic stressors. Methods: Higher overall expression of C/EBPδ in the luteal phase of the menstrual cycle prompted us to investigate the role of C/EBPδ in carcinogenesis. In vitro experiments were conducted in fallopian tube cell samples and cancer cell lines to investigate the role of C/EBPδ in proliferation, migration, and the epithelial to mesenchymal transition. Findings: Expression of C/EBPδ induced premature cellular arrest and decreased soft agar colony formation. Loss of C/EBPδ in epithelial cancer cell lines did not have significant effects on proliferation, yet overexpression demonstrated downregulation of growth, similar to normal fallopian tube cells. C/EBPδ promoted a partial mesenchymal to epithelial (MET) phenotype by upregulating E-cadherin and downregulating Vimentin and N-cadherin in FTE cells and increased migratory activity, which suggests a regulatory role in the epithelial-mesenchymal plasticity of these cells. Interpretation: Our findings suggest that C/EBPδ regulates the phenotype of normal fallopian tube cells by acting on downstream regulatory factors that are implicated in the development of ovarian serous carcinogenesis. FUND: This study was funded by the CDMRP Ovarian Cancer program (W81WH-0701-0371, W81XWH-18-1-0072), the Princess Margaret Cancer Centre Foundation, Foundation for Women's Cancer - The Belinda-Sue/Mary-Jane Walker Fund, Colleen's Dream Foundation and Sylvester Comprehensive Cancer Center.
MeSH term(s)	Biomarkers, Tumor ; CCAAT-Enhancer-Binding Protein-delta/metabolism ; Carcinoma/etiology ; Carcinoma/metabolism ; Carcinoma/pathology ; Cell Line, Tumor ; Cell Movement/genetics ; Cell Transformation, Neoplastic/genetics ; Cell Transformation, Neoplastic/metabolism ; Epithelial-Mesenchymal Transition/genetics ; Female ; Gene Expression ; Humans ; Immunohistochemistry ; Models, Biological ; Mucous Membrane/metabolism ; Mucous Membrane/pathology ; Neoplasm Grading ; Phenotype ; RNA Interference
Chemical Substances	Biomarkers, Tumor ; CCAAT-Enhancer-Binding Protein-delta (142662-43-9)
Language	English
Publishing date	2019-05-09
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2851331-9
ISSN	2352-3964
ISSN (online)	2352-3964
DOI	10.1016/j.ebiom.2019.05.002
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Article: Potent virucidal activity of honeybee “Apis mellifera” venom against Hepatitis C Virus

Sarhan, Moustafa / El-Bitar, Alaa M.H / Hotta, Hak

Toxicon. 2020 Dec., v. 188

2020

Abstract: Hepatitis C virus (HCV) is a global viral widespread without an available vaccine to prevent ...

Abstract	Hepatitis C virus (HCV) is a global viral widespread without an available vaccine to prevent infection. HCV infection can cause serious liver diseases such as hepatocellular carcinoma (HCC). Current treatment of HCV infection depends on the FDA approved direct-acting antivirals (DAAs) which have side effects and expensive. Thus, development of a novel, more efficient, along with affordable pricing anti-HCV agents is still required. The purpose of the present study is to evaluate the antiviral effects of bee venom (BV) from the honeybee Apis mellifera on the HCV replication life cycle. The crude venom and its components were examined for their anti-HCV activities using Huh7it-1 cultured cells and the JFH1 strain of HCV genotype 2a. Results revealed that BV inhibited HCV infection with 50% inhibitory concentration (IC₅₀) of 0.05 ng/ml, while the 50% cytotoxic concentration (CC₅₀) being 20,000 ng/ml. The venom directly blocked HCV/cell entry by acting on virus particles in a dose dependent manner, whereas no interference on the host cells. Furthermore, venom showed no inhibitory effect on HCV replication and release. Interestingly, none of the main BV components including the mast cell degranulating peptide (MCD), mpamin, or the small peptides melittin (MLT) showed anti-HCV activity up to 5 μg/ml. In conclusion, these results suggest that BV has a direct virucidal activity against HCV and may exert its antiviral effect through a non-common peptide(s) or toxin complex within the crude venom. Therefore, the crude BV can be considered as a promising candidate for characterization and development of new and natural anti-HCV therapeutic agents.
Keywords	Apis mellifera ; Hepatitis C virus ; antiviral agents ; antiviral properties ; bee venoms ; cytotoxicity ; dose response ; genotype ; hepatoma ; honey bees ; inhibitory concentration 50 ; liver ; mast cells ; melittin ; peptides ; therapeutics ; toxins ; vaccines ; viruses
Language	English
Dates of publication	2020-12
Size	p. 55-64.
Publishing place	Elsevier Ltd
Document type	Article
Note	NAL-AP-2-clean
ZDB-ID	204479-1
ISSN	1879-3150 ; 0041-0101
ISSN (online)	1879-3150
ISSN	0041-0101
DOI	10.1016/j.toxicon.2020.10.014
Database	NAL-Catalogue (AGRICOLA)

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Article: Comparison of cystatin C and creatinine-based estimated glomerular filtration rate equations among elderly chronic kidney disease patients attending a tertiary care hospital: A prospective cross-sectional study .

Khan, Irfanullah / Khan, Amer Hayat / Adnan, Azreen Syazril / Naqvi, Atta Abbas / Rehman, Anees Ur / Ahmad, Nafees / Ishaqui, Azfar Athar / Bitar, Ahmad Naoras

Clinical nephrology

2020 Volume 93, Issue 5, Page(s) 217–226

Abstract: ... chronic kidney disease (CKD) staging in the elderly population. Serum cystatin C is believed to more accurately define ... Architect-C8000 (Jaffe method). While serum cystatin C was examined by Human cystatin C ELISA kit (Sigma ... the creatinine- and cystatin C-based equations. Creatinine-based equations classify patients as having CKD stage ...

Abstract	Background: Serum creatinine has been solely used in clinical practice to identify chronic kidney disease (CKD) staging in the elderly population. Serum cystatin C is believed to more accurately define the CKD staging and is also ratified as an endogenous biomarker by Kidney Disease Improving Global Outcomes (KDIGO) guidelines. Material and methods: A total of 300 elderly Malay participants (age ≥ 65 years) with CKD, attending the Hospital University Sains Malaysia were included in the study. Demographic data and history were also recorded. Serum creatinine was assayed by Chemistry Analyzer Model Architect-C8000 (Jaffe method). While serum cystatin C was examined by Human cystatin C ELISA kit (Sigma-Aldrich) using Thermo Scientific Varioskan Flash ELISA reader. Results: Out of 300 study participants, 169 (56.3%) were females. Mean age of patients was 67.6 ± 6.7 years. 64 male (64.6%) and 35 female (35.4%) patients were between 70 and 79 years. When estimated by MDRD equation, the prevalence of CKD stage 3 (defined as eGFR = 30 - 59 mL/min/1.73m Conclusion: The staging of CKD is different between the creatinine- and cystatin C-based equations. Creatinine-based equations classify patients as having CKD stage 5 twice as often as cystatin C-based equations.
MeSH term(s)	Aged ; Aged, 80 and over ; Creatinine/blood ; Cross-Sectional Studies ; Cystatin C/blood ; Female ; Glomerular Filtration Rate ; Humans ; Male ; Prospective Studies ; Renal Insufficiency, Chronic/physiopathology ; Tertiary Care Centers
Chemical Substances	Cystatin C ; Creatinine (AYI8EX34EU)
Language	English
Publishing date	2020-03-17
Publishing country	Germany
Document type	Comparative Study ; Journal Article
ZDB-ID	185101-9
ISSN	0301-0430
ISSN	0301-0430
DOI	10.5414/CN109573
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Article ; Online: CCAAT/enhancer binding protein delta (C/EBPδ) demonstrates a dichotomous role in tumour initiation and promotion of epithelial carcinomaResearch in context

Ramlogan Sowamber / Rania Chehade / Mahmoud Bitar / Leah V. Dodds / Anca Milea / Brian Slomovitz / Patricia A. Shaw / Sophia H.L. George

EBioMedicine, Vol 44, Iss , Pp 261-

2019 Volume 274

Abstract	Background: CCAAT/enhancer binding protein delta (C/EBPδ,CEBPD), a gene part of the highly conserved basic-leucine zipper (b-ZIP) domain of transcriptional factors, is downregulated in 65% of high grade serous carcinomas of the ovary (HGSC). Overexpression of C/EBPδ in different tumours, such as glioblastoma and breast cancer either promotes tumour progression or inhibits growth and has low expression in normal tissue until activated by cytotoxic stressors. Methods: Higher overall expression of C/EBPδ in the luteal phase of the menstrual cycle prompted us to investigate the role of C/EBPδ in carcinogenesis. In vitro experiments were conducted in fallopian tube cell samples and cancer cell lines to investigate the role of C/EBPδ in proliferation, migration, and the epithelial to mesenchymal transition. Findings: Expression of C/EBPδ induced premature cellular arrest and decreased soft agar colony formation. Loss of C/EBPδ in epithelial cancer cell lines did not have significant effects on proliferation, yet overexpression demonstrated downregulation of growth, similar to normal fallopian tube cells. C/EBPδ promoted a partial mesenchymal to epithelial (MET) phenotype by upregulating E-cadherin and downregulating Vimentin and N-cadherin in FTE cells and increased migratory activity, which suggests a regulatory role in the epithelial-mesenchymal plasticity of these cells. Interpretation: Our findings suggest that C/EBPδ regulates the phenotype of normal fallopian tube cells by acting on downstream regulatory factors that are implicated in the development of ovarian serous carcinogenesis. Fund: This study was funded by the CDMRP Ovarian Cancer program (W81WH-0701-0371, W81XWH-18-1-0072), the Princess Margaret Cancer Centre Foundation, Foundation for Women's Cancer – The Belinda-Sue/Mary-Jane Walker Fund, Colleen's Dream Foundation and Sylvester Comprehensive Cancer Center. Keywords: C/EBPδ, High-grade serous ovarian cancer, Fallopian tube epithelia, Epithelial to mesenchymal transition
Keywords	Medicine ; R ; Medicine (General) ; R5-920
Subject code	570
Language	English
Publishing date	2019-06-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
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Article ; Online: Misregulation of the broad-range phospholipase C activity increases the susceptibility of Listeria monocytogenes to intracellular killing by neutrophils.

Blank, Bryant S / Abi Abdallah, Delbert S / Park, Justin J / Nazarova, Evgeniya V / Pavinski Bitar, Alan / Maurer, Kirk J / Marquis, Hélène

Microbes and infection

2014 Volume 16, Issue 2, Page(s) 104–113

Abstract: ... the ability to control the activity of a phospholipase C (PC-PLC) is attenuated a hundred fold in mice ...

Abstract	Listeria monocytogenes is a facultative intracellular bacterial pathogen that tightly regulates the activities of various virulence factors during infection. A mutant strain (the plcBDpro mutant) that has lost the ability to control the activity of a phospholipase C (PC-PLC) is attenuated a hundred fold in mice. This attenuation is not due to a lack of bacterial fitness, but appears to result from a modified host response to infection. The transcriptomic pattern of immune-related genes indicated that PC-PLC did not enhance the innate immune response in infected macrophages. However, it partially protected the cells from bacteria-mediated mitochondrial fragmentation. In mice, the plcBDpro mutant transiently caused an increase in liver pathology, as judged by the size of neutrophil-filled micro-abscesses. Moreover, the plcBDpro mutant was more susceptible to intracellular killing by neutrophils than wild-type L. monocytogenes. Together, these data indicate that in vivo attenuation of the plcBDpro mutant results from its reduced ability to disrupt mitochondrial homeostasis and to resist intracellular killing by neutrophils.
MeSH term(s)	Animals ; Female ; Listeria monocytogenes/enzymology ; Listeria monocytogenes/genetics ; Listeria monocytogenes/immunology ; Mice ; Mice, Inbred BALB C ; Microbial Viability ; Neutrophils/immunology ; Neutrophils/microbiology ; Type C Phospholipases/genetics ; Type C Phospholipases/metabolism ; Virulence Factors/genetics ; Virulence Factors/metabolism
Chemical Substances	Virulence Factors ; Type C Phospholipases (EC 3.1.4.-)
Language	English
Publishing date	2014-02-10
Publishing country	France
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	1465093-9
ISSN	1769-714X ; 1286-4579
ISSN (online)	1769-714X
ISSN	1286-4579
DOI	10.1016/j.micinf.2013.10.014
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Zs.A 5014: Show issues

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Article ; Online: Parental refusal of prenatal screening for aneuploidies.

Bitar, Lynn / Chaccour, Christian / Bitar, Elio R / Halabi, Rami / Kesrouani, Assaad

Journal of perinatal medicine

2024

Abstract: Objectives: To analyze the reasons for refusal of aneuploidy screening in a multicultural Middle Eastern population.: Methods: The study included patients delivering in a university hospital, who had refused aneuploidy screening during their ... ...

Abstract	Objectives: To analyze the reasons for refusal of aneuploidy screening in a multicultural Middle Eastern population. Methods: The study included patients delivering in a university hospital, who had refused aneuploidy screening during their pregnancy. We evaluated through a questionnaire submitted during the postpartum period the sociodemographic characteristics, beliefs, attitudes, and the main reason underpinning their choice. Religious, ethical, and financial factors, personal beliefs, medical information, perceived media information, and familial input were assessed through a Likert scale. Results: Our pilot study included 70 patients. The main reason (33 %) was the refusal to terminate pregnancy if the screening tests ultimately led to a diagnosis of aneuploidy. Lack of adequate information on the availability and benefits of this screening method (28 %), religious beliefs (17 %), in addition to other minor reasons such as financial considerations, familial recommendations, late pregnancy follow-ups, and media influence were also identified as contributing factors. Conclusions: Aneuploidy screening is routinely offered to couples, with varying uptake rates observed worldwide. Sufficient information on prenatal screening and diagnosis should be provided to all pregnant women, presenting all available options, thus enabling them to make a free and informed choice during their pregnancy.
Language	English
Publishing date	2024-03-15
Publishing country	Germany
Document type	Journal Article
ZDB-ID	123512-6
ISSN	1619-3997 ; 0300-5577 ; 0936-174X
ISSN (online)	1619-3997
ISSN	0300-5577 ; 0936-174X
DOI	10.1515/jpm-2023-0399
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Article: Two cases of intraoperative diagnosed Amyand hernia: Case report and literature review.

Ghattas, Souad / El Bitar, Jad / Hadeer, Ribal Aby / Salloum, Maher / Akel, Carl / Bitar, Henri

International journal of surgery case reports

2024 Volume 118, Page(s) 109560

Abstract: Introduction: Amyand hernia is the presence of an incarcerated vermiform appendix (either inflamed or not) within the hernia sac. This type of hernia is very rare with an incidence reported to be 0.5 to 1 % and even rarer in adults.: Cases ... ...

Abstract	Introduction: Amyand hernia is the presence of an incarcerated vermiform appendix (either inflamed or not) within the hernia sac. This type of hernia is very rare with an incidence reported to be 0.5 to 1 % and even rarer in adults. Cases presentation: We present here two cases of male patients found the have an Amyand Hernia diagnosed incidentally intraoperatively, and managed with appendectomy and mesh herniorrhaphy. Clinical discussion: For the management of this type of hernia, in general, the surgeon should perform an appendectomy with the repair to prevent future herniation or appendicitis, but some opinions differ, and state that when there are no signs of inflammation, it is not required to perform a preventative appendectomy. Conclusion: The decision on how to manage depends on multiple factors including inflammation of the appendix, the possibility of abdominal sepsis, and the patient comorbidities. The status of the appendix determines whether to undergo hernia repair with or without mesh.
Language	English
Publishing date	2024-03-22
Publishing country	Netherlands
Document type	Case Reports
ISSN	2210-2612
ISSN	2210-2612
DOI	10.1016/j.ijscr.2024.109560
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