Browsing by Author "Saadeldin M.K."

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Effects of Turmeric (Curcuma longa) Extract in streptozocin-induced diabetic model
(Blackwell Publishing Ltd, 2019) Essa R.; El Sadek A.M.; Baset M.E.; Rawash M.A.; Sami D.G.; Badawy M.T.; Mansour M.E.; Attia H.; Saadeldin M.K.; Abdellatif A.; Faculty of Biotechnology; October University for Modern Sciences and Arts; 6th October City; Egypt; Biotechnology Graduate Program; School of Sciences and Engineering; American University in Cairo; New Cairo; Egypt; Faculty of Medicine; Department of Anatomy; Al-Azhar University; Damietta; Egypt; Faculty of Physical Therapy; Horus University; Damietta; Egypt; Department of Experimental Oncology; European Institute of Oncology; Milan; Italy; Department of Biology; School of Sciences and Engineering; American University in Cairo; New Cairo; Egypt
Herbal remedies have been used for centuries to ameliorate complications of diabetes mellitus (DM). The aim of this study is to compare the effects of the oral curcumin supplement versus parenteral administration of turmeric extract on diabetic complications in a streptozocin (STZ) diabetic model. STZ DM rats received low and high doses turmeric extract intraperitoneally as well as oral curcumin. Curcumin and turmeric extracts significantly reduced blood glucose and creatinine levels, but not urea, and caused an increase in uric acid. Low dose improved liver enzymes, while higher dose and oral administration caused an increase in the ALT and AST. All groups showed an improvement in the serum cholesterol, while the triglycerides were not improved in the high and oral treatment. Histological evaluation showed islet cell protection. High-dose injection showed almost intact renal corpuscles as well as tubular structures with minimal degeneration. Treatment showed limited protection of Liver tissue. Practical application: Curcumin has been heavily marketed as a protective agent. The current study shows some potential risk of curcumin use. Oral and injectable curcumin should be used with caution. Turmeric extract and oral curcumin supplement showed protective effects on pancreatic, and renal structure and function. Although both did show some improvement in liver function, higher doses caused disturbance in liver enzymes and did not show histological evidence of liver tissue protection. � 2019 Wiley Periodicals, Inc.
Preclinical models of breast cancer: Two-way shuttles for immune checkpoint inhibitors from and to patient bedside
(Elsevier Ltd, 2019) Abdel-Aziz A.K.; Saadeldin M.K.; D'Amico P.; Orecchioni S.; Bertolini F.; Curigliano G.; Minucci S.; Department of Experimental Oncology; IEO; European Institute of Oncology IRCCS; Milan; Italy; Department of Pharmacology and Toxicology; Faculty of Pharmacy; Ain Shams University; Cairo; Egypt; Faculty of Biotechnology; October University for Modern Sciences and Arts; 6th October City; Cairo; Egypt; Division of Early Drug Development for Innovative Therapies; IEO; European Institute of Oncology IRCCS; Milan; Italy; Laboratory of Hematology-Oncology; IEO; European Institute of Oncology IRCCS; Milan; Italy; Department of Oncology and Hemato-Oncology; University of Milano; Milan; Italy; Department of Biosciences; University of Milan; Milan; Italy
The Food and Drug Administration has lately approved atezolizumab, anti-programmed death ligand 1 (PD-L1), to be used together with nanoparticle albumin-bound (nab) paclitaxel in treating patients with triple negative breast cancer (BC) expressing PD-L1. Nonetheless, immune checkpoint inhibitors (ICIs) are still challenged by the resistance and immune-related adverse effects evident in a considerable subset of treated patients without conclusive comprehension of the underlying molecular basis, biomarkers and tolerable therapeutic regimens capable of unleashing the anti-tumour immune responses. Stepping back to preclinical models is thus inevitable to address these inquiries. Herein, we comprehensively review diverse preclinical models of BC exploited in investigating ICIs underscoring their pros and cons as well as the learnt and awaited lessons to allow full exploitation of ICIs in BC therapy. 2019 Elsevier Ltd
Serum sclerostin and irisin as predictive markers for atherosclerosis in Egyptian type II diabetic female patients: A case control study
(Public Library of Science, 2018) Saadeldin M.K.; Elshaer S.S.; Emara I.A.; Maged M.; Abdel-Aziz A.K.; Department of Biochemistry; Faculty of Pharmacy (Girls); Al-Azhar University; Cairo; Egypt; Department of Biochemistry; National Institute of Diabetes and Endocrinology (NIDE); Cairo; Egypt; Faculty of Biotechnology; October University for Modern Sciences and Arts; 6th October City; Cairo; Egypt; Department of Experimental Oncology; European Institute of Oncology; Milan; Italy
Diabetes mellitus represents a major independent risk factor for developing fatal cardiovascular diseases (CVDs) presumably through accelerating atherosclerosis; the underlying cause of most CVDs. Notably, this relative risk is reported to be higher in women than men. Endeavors directed towards identifying novel reliable predictive biomarkers are immensely thereby urged to improve the long-term outcome in these diabetic female patients. Sclerostin (SOST) is a Wnt signaling antagonist whereas irisin is a muscle-derived factor released after exercising which enhances browning of white adipose tissue. Emerging lines of evidence hint at potential crosstalk between them and CVDs. The present study aimed to assess the serum levels of SOST and irisin in Egyptian type 2 diabetic (T2DM) female patients with and without atherosclerosis and explore the possible relationship between both markers and other studied parameters among the studied cohorts. In this case-control study, 69 female subjects were enrolled; 39 type 2 diabetes patients with atherosclerosis (T2DM+ATHR), 22 type 2 diabetes patients without atherosclerosis (T2DM-ATHR) and 8 healthy controls. Their serum levels of SOST and irisin were assessed using ELISA. Significant increase in SOST levels were found in T2DM+ATHR compared to T2DM-ATHR and control (259.9 �17.98 vs. 165.8�13.12 and 142.0�13.31 pg/mL respectively, P0.001). Conversely, irisin levels were significantly lower in T2DM+ATHR (P0.001) and T2DM-ATHR (P0.01) compared to the control group (32.91�2.545 and 58.55�13.19 vs. 473.6�112.7 pg/ mL). Interestingly, significant correlations between the levels of SOST and both irisin and fasting blood glucose were noticed in T2DM+ATHR group (r = 0.3754 and 0.3381 respectively, P0.05). In conclusion, to the best of our knowledge, this study is the first to demonstrate the correlation between SOST and irisin levels in atherosclerotic T2DM female patients implying their potential implication in diabetic cardiovascular pathophysiology and supporting their use as reliable diagnostic/prognostic biomarkers for monitoring and preventing CVDs progression of T2DM female patients. � 2018 Saadeldin 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.
Thermal stability of a mercuric reductase from the Red Sea Atlantis II hot brine environment as analyzed by site-directed mutagenesis
(American Society for Microbiology, 2019) Maged M.; Hosseiny A.E.; Saadeldin M.K.; Aziz R.K.; Ramadan E.; Department of Biology; School of Sciences and Engineering; The American University in Cairo; New Cairo; Egypt; Department of Microbiology and Immunology; Faculty of Pharmacy; Cairo University; Cairo; Egypt; Faculty of Pharmacy; The British University in Egypt (BUE); El Shorouk; Egypt; Science and Technology Research Center; School of Sciences and Engineering; The American University in Cairo; New Cairo; Egypt; Faculty of Biotechnology; October University for Modern Sciences and Arts; 6th October City; Cairo; Egypt
The lower convective layer (LCL) of the Atlantis II brine pool of the Red Sea is a unique environment in terms of high salinity, temperature, and high concentrations of heavy metals. Mercuric reductase enzymes functional in such extreme conditions could be considered a potential tool in the environmental detoxification of mercurial poisoning and might alleviate ecological hazards in the mining industry. Here, we constructed a mercuric reductase library from Atlantis II, from which we identified genes encoding two thermostable mercuric reductase (MerA) isoforms: one is halophilic (designated ATII-LCL) while the other is not (designated ATII-LCLNH). The ATII-LCL MerA has a short motif composed of four aspartic acids (4D414- 417) and two characteristic signature boxes that played a crucial role in its thermal stability. To further understand the mechanism behind the thermostability of the two studied enzymes, we mutated the isoform ATII-LCL-NH and found that the substitution of 2 aspartic acids (2D) at positions 415 and 416 enhanced the thermal stability, while other mutations had the opposite effect. The 2D mutant showed superior thermal tolerance, as it retained 81% of its activity after 10 min of incubation at 70�C. A three-dimensional structure prediction revealed newly formed salt bridges and H bonds in the 2D mutant compared to the parent molecule. To the best of our knowledge, this study is the first to rationally design a mercuric reductase with enhanced thermal stability, which we propose to have a strong potential in the bioremediation of mercurial poisoning. � 2019 American Society for Microbiology.