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Article ; Online: Angiotensin II

Sameh Saber

Bulletin of the National Research Centre, Vol 42, Iss 1, Pp 1-

a key mediator in the development of liver fibrosis and cancer

2018 Volume 7

Abstract: Abstract Background Liver fibrosis and its outcomes of cirrhosis and hepatocellular carcinoma are major worldwide health problems and due to the complicated molecular pathogenesis, the options for effective systemic cure are relatively restricted. ... ...

Abstract	Abstract Background Liver fibrosis and its outcomes of cirrhosis and hepatocellular carcinoma are major worldwide health problems and due to the complicated molecular pathogenesis, the options for effective systemic cure are relatively restricted. Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers, having well established safety profiles and low economic costs, may provide synergistic effects to existing chemotherapies by reducing angiotensin II-mediated angiogenesis, fibrogenesis, mitogenesis, metastasis, and oxidative stress. Conclusion These effects suggest angiotensin II inhibitors as promising agents for further clinical trials in the management of patients with fibrotic diseases.
Keywords	Fibrosis ; Hepatocellular carcinoma ; Renin-angiotensin system ; Angiotensin II ; Science ; Q
Language	English
Publishing date	2018-11-01T00:00:00Z
Publisher	SpringerOpen
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Evaluation of the Corneal Endothelium Following Cataract Surgery in Diabetic and Non-Diabetic Patients

Adela-Laura Ciorba / George Roiu / Amir Mohamed Abdelhamid / Sameh Saber / Simona Cavalu

Diagnostics, Vol 13, Iss 1115, p

2023 Volume 1115

Abstract: The aim of this study was to evaluate the influence of phacoemulsification cataract surgery on the state of the corneal endothelium in diabetic versus non-diabetic patients. We compared the corneal cell morphology in 48 diabetics with good glycemic ... ...

Abstract	The aim of this study was to evaluate the influence of phacoemulsification cataract surgery on the state of the corneal endothelium in diabetic versus non-diabetic patients. We compared the corneal cell morphology in 48 diabetics with good glycemic control and 72 non-diabetic patients before and after uneventful phacoemulsification. Corneal cell density, central corneal thickness, and hexagonality were measured preoperatively and post-surgery (at 1 and 4 weeks) by specular microscopy. The effect of age, gender, axial length, and anterior chamber depth on the parameters of the corneal endothelium were evaluated. We noticed a drop in the endothelial density in both groups postoperatively: a mean endothelial cell loss of 472.7 ± 369.1 in the diabetic group was recorded versus 165.7 ± 214.6 mean loss in the non-diabetic group after the first week. A significant increase in central corneal thickness was also noticed in both groups one week after phacoemulsification, but no statistical significance after 4 weeks in the diabetic group. In terms of cell hexagonality, statistically significant differences were noticed after 4 weeks in both groups. Overall, a significant difference between diabetic and non-diabetic population was noticed in terms of corneal endothelial cell loss after uneventful phacoemulsification cataract surgery. Routine specular microscopy and HbA1c evaluation is recommended before cataract surgery, while intraoperative precautions and high monitorisation in terms of pacho power intensity and ultrasound energy, along with a proper application of the dispersive viscoelastic substances are essential to reduce the risk of endothelial damage.
Keywords	diabetes ; cataract surgery ; phacoemulsification ; corneal endothelium ; cell density ; Medicine (General) ; R5-920
Subject code	571
Language	English
Publishing date	2023-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Author Correction

Nancy S. Younis / Amal M. H. Ghanim / Sameh Saber

Scientific Reports, Vol 12, Iss 1, Pp 1-

Mebendazole augments sensitivity to sorafenib by targeting MAPK and BCL-2 signalling in n-nitrosodiethylamine-induced murine hepatocellular carcinoma

2022 Volume 3

Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2022-08-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Fluid Status by Inferior Vena Cava Collapsibility Index, Chest Ultrasound and Bioimpedance Spectroscopy in Children and Adolescents on Chronic Hemodialysis.

Gohary, Amal Elsaid / Shokry, Dina Mahamoud / Saleh, Safaa Hamdy / Baiomy, Sameh Saber / Gehad, Mona Hamed

Indian journal of pediatrics

2023 Volume 90, Issue 8, Page(s) 838

MeSH term(s)	Humans ; Child ; Adolescent ; Vena Cava, Inferior/diagnostic imaging ; Ultrasonography/methods ; Renal Dialysis/adverse effects ; Spectrum Analysis
Language	English
Publishing date	2023-06-02
Publishing country	India
Document type	Letter
ZDB-ID	218231-2
ISSN	0973-7693 ; 0019-5456
ISSN (online)	0973-7693
ISSN	0019-5456
DOI	10.1007/s12098-023-04625-6
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Article ; Online: Role of Ganetespib, an HSP90 Inhibitor, in Cancer Therapy

Mahmoud E. Youssef / Simona Cavalu / Alexandru Madalin Hasan / Galal Yahya / Marwa A. Abd-Eldayem / Sameh Saber

International Journal of Molecular Sciences, Vol 24, Iss 5014, p

From Molecular Mechanisms to Clinical Practice

2023 Volume 5014

Abstract: Heat-shock proteins are upregulated in cancer and protect several client proteins from degradation. Therefore, they contribute to tumorigenesis and cancer metastasis by reducing apoptosis and enhancing cell survival and proliferation. These client ... ...

Abstract	Heat-shock proteins are upregulated in cancer and protect several client proteins from degradation. Therefore, they contribute to tumorigenesis and cancer metastasis by reducing apoptosis and enhancing cell survival and proliferation. These client proteins include the estrogen receptor (ER), epidermal growth factor receptor (EGFR), insulin-like growth factor-1 receptor (IGF-1R), human epidermal growth factor receptor 2 (HER-2), and cytokine receptors. The diminution of the degradation of these client proteins activates different signaling pathways, such as the PI3K/Akt/NF-κB, Raf/MEK/ERK, and JAK/STAT3 pathways. These pathways contribute to hallmarks of cancer, such as self-sufficiency in growth signaling, an insensitivity to anti-growth signals, the evasion of apoptosis, persistent angiogenesis, tissue invasion and metastasis, and an unbounded capacity for replication. However, the inhibition of HSP90 activity by ganetespib is believed to be a promising strategy in the treatment of cancer because of its low adverse effects compared to other HSP90 inhibitors. Ganetespib is a potential cancer therapy that has shown promise in preclinical tests against various cancers, including lung cancer, prostate cancer, and leukemia. It has also shown strong activity toward breast cancer, non-small cell lung cancer, gastric cancer, and acute myeloid leukemia. Ganetespib has been found to cause apoptosis and growth arrest in these cancer cells, and it is being tested in phase II clinical trials as a first-line therapy for metastatic breast cancer. In this review, we will highlight the mechanism of action of ganetespib and its role in treating cancer based on recent studies.
Keywords	ganetespib ; HSP90 ; cancer ; EGFR ; IGF-1 ; VEGF ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	610 ; 616
Language	English
Publishing date	2023-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Unlocking the Full Potential of SGLT2 Inhibitors

Mahmoud E. Youssef / Galal Yahya / Mihaela Simona Popoviciu / Simona Cavalu / Marwa A. Abd-Eldayem / Sameh Saber

International Journal of Molecular Sciences, Vol 24, Iss 6039, p

Expanding Applications beyond Glycemic Control

2023 Volume 6039

Abstract: The number of diabetic patients has risen dramatically in recent decades, owing mostly to the rising incidence of type 2 diabetes mellitus (T2DM). Several oral antidiabetic medications are used for the treatment of T2DM including, α-glucosidases ... ...

Abstract	The number of diabetic patients has risen dramatically in recent decades, owing mostly to the rising incidence of type 2 diabetes mellitus (T2DM). Several oral antidiabetic medications are used for the treatment of T2DM including, α-glucosidases inhibitors, biguanides, sulfonylureas, meglitinides, GLP-1 receptor agonists, PPAR-γ agonists, DDP4 inhibitors, and SGLT2 inhibitors. In this review we focus on the possible effects of SGLT2 inhibitors on different body systems. Beyond the diabetic state, SGLT2 inhibitors have revealed a demonstrable ability to ameliorate cardiac remodeling, enhance myocardial function, and lower heart failure mortality. Additionally, SGLT2 inhibitors can modify adipocytes and their production of cytokines, such as adipokines and adiponectin, which enhances insulin sensitivity and delays diabetes onset. On the other hand, SGLT2 inhibitors have been linked to decreased total hip bone mineral deposition and increased hip bone resorption in T2DM patients. More data are needed to evaluate the role of SGLT2 inhibitors on cancer. Finally, the effects of SGLT2 inhibitors on neuroprotection appear to be both direct and indirect, according to scientific investigations utilizing various experimental models. SGLT2 inhibitors improve vascular tone, elasticity, and contractility by reducing oxidative stress, inflammation, insulin signaling pathways, and endothelial cell proliferation. They also improve brain function, synaptic plasticity, acetylcholinesterase activity, and reduce amyloid plaque formation, as well as regulation of the mTOR pathway in the brain, which reduces brain damage and cognitive decline.
Keywords	SGLT2 inhibitors ; cardiovascular effects ; cardiorenal effects ; cancer ; bone minerals ; cognitive effects ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	616
Language	English
Publishing date	2023-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Novel Potent and Selective DPP-4 Inhibitors

Ahmed A. E. Mourad / Ahmed E. Khodir / Sameh Saber / Mai A. E. Mourad

Pharmaceuticals, Vol 14, Iss 2, p

Design, Synthesis and Molecular Docking Study of Dihydropyrimidine Phthalimide Hybrids

2021 Volume 144

Abstract: Background: Dipeptidyl peptidase-4 (DPP-4) inhibitors have emerged as anti-hyperglycemic agents that improve glycemic control in type 2 diabetic patients, either as monotherapy or in combination with other antidiabetic drugs. Methods: A novel series of ... ...

Abstract	Background: Dipeptidyl peptidase-4 (DPP-4) inhibitors have emerged as anti-hyperglycemic agents that improve glycemic control in type 2 diabetic patients, either as monotherapy or in combination with other antidiabetic drugs. Methods: A novel series of dihydropyrimidine phthalimide hybrids was synthesized and evaluated for their in vitro and in vivo DPP-4 inhibition activity and selectivity using alogliptin as reference. Oral glucose tolerance test was assessed in type 2 diabetic rats after chronic treatment with the synthesized hybrids ± metformin. Cytotoxicity and antioxidant assays were performed. Additionally, molecular docking study with DPP-4 and structure activity relationship of the novel hybrids were also studied. Results: Among the synthesized hybrids, 10g , 10i , 10e , 10d and 10b had stronger in vitro DPP-4 inhibitory activity than alogliptin. Moreover, an in vivo DPP-4 inhibition assay revealed that 10g and 10i have the strongest and the most extended blood DPP-4 inhibitory activity compared to alogliptin. In type 2 diabetic rats, hybrids 10g , 10i and 10e exhibited better glycemic control than alogliptin, an effect that further supported by metformin combination. Finally, 10j , 10e , 10h and 10d had the highest radical scavenging activity in DPPH assay. Conclusions: Hybrids 10g , 10i and 10e are potent DPP-4 inhibitors which may be beneficial for T2DM treatment.
Keywords	DPP-4 inhibitors ; T2DM ; OGTT ; DPPH ; dihydropyrimidine ; phthalimide ; Medicine ; R ; Pharmacy and materia medica ; RS1-441
Subject code	570
Language	English
Publishing date	2021-02-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Mebendazole augments sensitivity to sorafenib by targeting MAPK and BCL-2 signalling in n-nitrosodiethylamine-induced murine hepatocellular carcinoma

Nancy S. Younis / Amal M. H. Ghanim / Sameh Saber

Scientific Reports, Vol 9, Iss 1, Pp 1-

2019 Volume 16

Abstract: Abstract Sorafenib (SO) is a multi-kinase inhibitor that targets upstream signals in the MAPK pathway. Drug resistance and transient survival benefits are the main obstacles associated with SO treatment in Hepatocellular carcinoma (HCC) patients. ... ...

Abstract	Abstract Sorafenib (SO) is a multi-kinase inhibitor that targets upstream signals in the MAPK pathway. Drug resistance and transient survival benefits are the main obstacles associated with SO treatment in Hepatocellular carcinoma (HCC) patients. Mebendazole (MBZ), an anthelmintic agent, has demonstrated activity against various cancer types. Therefore, we aimed to investigate the possible mechanisms of MBZ other than its anti-tubulin activity. MBZ (100 mg/kg/day, P.O.) was administered to N-nitrosodiethylamine-induced HCC mice as a monotherapeutic agent or in combination with SO. Our results revealed that MBZ decreased AFP levels, improved liver function and histology and increased survival in HCC mice, particularly when administered in combination with SO. MBZ also reduced hepatic inflammation and fibrogenesis as evidenced by reductions in TNF-α and TGF-β1 levels, respectively. Increased hepatic caspases-3 and -9 and decreased BCL-2 levels suggest induced-cell death. In addition, MBZ demonstrated anti-angiogenic, anti-metastatic, and anti-proliferative effects, as indicated by reduced VEGF levels, MMP-2:TIMP-1 ratios, and reduced cyclin D1 levels and Ki67 immunostaining, respectively. Our main finding was that MBZ targeted downstream signal of the MAPK pathway by inhibiting ERK1/2 phosphorylation. Targeting downstream MAPK signalling by MBZ and upstream signalling by SO is a novel approach to minimizing resistance and prolonging survival.
Keywords	Medicine ; R ; Science ; Q
Subject code	570 ; 616
Language	English
Publishing date	2019-12-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Bioavailability and Antidiabetic Activity of Gliclazide-Loaded Cubosomal Nanoparticles

Mohamed Nasr / Saud Almawash / Ahmed Al Saqr / Alaa Y. Bazeed / Sameh Saber / Heba I. Elagamy

Pharmaceuticals, Vol 14, Iss 786, p

2021 Volume 786

Abstract: In this study, gliclazide-loaded cubosomal particles were prepared for improving the oral bioavailability and antidiabetic activity of gliclazide. Four formulations of gliclazide-loaded cubosomal nanoparticles dispersions were prepared by the ... ...

Abstract	In this study, gliclazide-loaded cubosomal particles were prepared for improving the oral bioavailability and antidiabetic activity of gliclazide. Four formulations of gliclazide-loaded cubosomal nanoparticles dispersions were prepared by the emulsification method using four different concentrations of glyceryl monooleate (GMO) and poloxamer 407 (P407) as the stabilizer. The prepared formulations were in vitro and in vivo evaluated. In vitro, the prepared gliclazide-loaded cubosomal dispersions exhibited disaggregated regular poly-angular particles with a nanometer-sized particle range from 220.60 ± 1.39 to 234.00 ± 2.90 nm and entrapped 73.84 ± 3.03 to 88.81 ± 0.94 of gliclazide. In vitro gliclazide release from cubosomal nanoparticles revealed an initially higher drug release during the first 2 h in acidic pH medium; subsequently, a comparatively higher drug release in alkaline medium relative to gliclazide suspension was observed. An in vivo absorption study in rats revealed a two-fold increase in the bioavailability of gliclazide cubosomal formulation relative to plain gliclazide suspension. Moreover, the study of in vivo hypoglycemic activity indicated that a higher percentage reduction in glucose level was observed after the administration of gliclazide cubosomal nanoparticles to rats. In conclusion, gliclazide-loaded cubosomal nanoparticles could be a promising delivery system for improving the oral absorption and antidiabetic activity of gliclazide.
Keywords	gliclazide ; BCS class II drug ; cubosomes ; bioavailability ; antidiabetic activity ; Medicine ; R ; Pharmacy and materia medica ; RS1-441
Subject code	500
Language	English
Publishing date	2021-08-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Liver Protective Effects of Renin-Angiotensin System Inhibition Have No Survival Benefits in Hepatocellular Carcinoma Induced By Repetitive Administration of Diethylnitrosamine in Mice

Sameh Saber / Amr Mahmoud / Noha Helal / Eman El-Ahwany / Rasha Abdelghany

Open Access Macedonian Journal of Medical Sciences, Vol 6, Iss 6, Pp 955-

2018 Volume 960

Abstract: BACKGROUND: Preclinical studies have demonstrated that renin-angiotensin system (RAS) signalling has strong tumour-promoting effects and RAS inhibition was associated with improvement in the overall survival in some cancer types including hepatocellular ... ...

Abstract	BACKGROUND: Preclinical studies have demonstrated that renin-angiotensin system (RAS) signalling has strong tumour-promoting effects and RAS inhibition was associated with improvement in the overall survival in some cancer types including hepatocellular carcinoma (HCC). OBJECTIVE: We aimed to investigate the effect of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin-II-receptor blockers (ARBs) on the survival of mice with diethylnitrosamine (DEN) induced HCC. METHODS: HCC was induced by weekly i.p. administration of DEN. Mice were treated with sorafenib (SO) (30 mg/kg), perindopril (PE) (1 mg/kg), fosinopril (FO) (2 mg/kg), losartan (LO) (10 mg/kg), PE (1 mg/kg) + SO (30 mg/kg), FO (2 mg/kg) + SO (30 mg/kg), or LO (10 mg/kg) + SO (30 mg/kg). Survival analysis was done using the Kaplan-Meier method, and the log-rank test was used for assessing the significance of difference between groups. RESULTS: The administration of PE, FO and LO as monotherapy or as combined with SO resulted in marked improvement in the liver histologic picture with no impact on overall survival of mice. CONCLUSION: Interfering the RAS either through the inhibition of ACE or the blockade of angiotensin II type 1 (AT1) receptors has similar effects on the liver of DEN-induced HCC mice and is not associated with longer survival due to detrimental effects of DEN on other organs. Hence, repetitive administration of DEN in such models of HCC is not suitable for mortality assessment studies.
Keywords	diethylnitrosamine ; hepatocellular carcinoma ; renin-angiotensin system ; survival analysis ; Medicine ; R
Subject code	616 ; 610
Language	English
Publishing date	2018-06-01T00:00:00Z
Publisher	ID Design 2012/DOOEL Skopje
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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