Publications by authors named "Mohamed Morsy"

184 Publications

Bioaccumulation and human health risk assessment of heavy metals in food crops irrigated with freshwater and treated wastewater: a case study in Southern Cairo, Egypt.

Environ Sci Pollut Res Int 2021 May 5. Epub 2021 May 5.

Deanship of Scientific Research, Umm Al-Qura University, Al Mukarramah, Makkah, Saudi Arabia.

Food safety has often attracted attention worldwide. Few studies have investigated the heavy metal (HM) pollution and health risk assessment of crops and vegetables. The current work was conducted to evaluate the human risk assessment of HM (Cu, Cd, Cr, Pb, and Zn) in radish, lettuce, tomato, onion, turnip, squash, okra, sunflower, Jews mallow, and garden rocket cultivated in treated wastewater (TWW)-irrigated sites as compared with those cultivated in freshwater (FW)-irrigated sites. Irrigation water, soil, and different plants were collected from 6 farmlands irrigated with TWW and two agricultural sites irrigated with FW (Nile river). Heavy metal transfer factor (HMTF), chronic daily intake of metals (CDIM), health hazard risk (HR), and health hazard index (HI) were estimated. The results showed that the tested HM levels in FW and TWW were below the Food and Agriculture Organization (FAO) and Egyptian standards recommended for irrigation. In soil samples, HM levels were below the permissible limits for both tested sites. The HM in soil and plants grew in TWW-irrigated sites possessed multiple levels higher than those grown in FW-irrigated sites. Among different plants, HM levels in the edible parts of plants grown in TWW-irrigated sites followed in decreasing order: tomato > sunflower >Jew's mallow = turnip = squash > lettuce > okra = radish > onion > garden rocket. The mean CDIM and HR values of plants irrigated using TWW were higher than those irrigated using FW. Furthermore, HR values for all plants grown in polluted and unpolluted sites were < 1 except Cd in plants grown in the TWW-irrigated farmlands. The mean HI for radish, lettuce, tomato, onion, turnip, squash, okra, sunflower, Jews mallow, and garden rocket grown in TWW-irrigated sites were 2.08, 2.39, 1.76, 1.53, 2.08, 1.80, 2.03, 1.91, 1.82, and 1.44 (for adult), and 2.39, 2.75, 2.71, 1.75, 2.38, 2.06, 2.33, 2.69, 2.10, and 1.65 (for children). Plants irrigated with TWW showed a higher HMTF than plants irrigated with FW. Jew's mallow and okra irrigated with TWW had a maximum HMTF. Consequently, different practical measures can be taken to minimize the HM levels in agricultural foodstuffs. These measures include preventing the excessive application of pesticides and fertilizers for crop production and continuous monitoring of different foodstuffs in the market.
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http://dx.doi.org/10.1007/s11356-021-14249-yDOI Listing
May 2021

Clarithromycin Solid Lipid Nanoparticles for Topical Ocular Therapy: Optimization, Evaluation and In Vivo Studies.

Pharmaceutics 2021 Apr 9;13(4). Epub 2021 Apr 9.

Department of Biomedical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi Arabia.

Solid lipid nanoparticles (SLNs) are being extensively exploited as topical ocular carrier systems to enhance the bioavailability of drugs. This study investigated the prospects of drug-loaded SLNs to increase the ocular permeation and improve the therapeutic potential of clarithromycin in topical ocular therapy. SLNs were formulated by high-speed stirring and the ultra-sonication method. Solubility studies were carried out to select stearic acid as lipid former, Tween 80 as surfactant, and Transcutol P as cosurfactant. Clarithromycin-loaded SLN were optimized by fractional factorial screening and 3 full factorial designs. Optimized SLNs (CL10) were evaluated for stability, morphology, permeation, irritation, and ocular pharmacokinetics in rabbits. Fractional factorial screening design signifies that the sonication time and amount of lipid affect the SLN formulation. A 3 full factorial design established that both factors had significant influences on particle size, percent entrapment efficiency, and percent drug loading of SLNs. The release profile of SLNs (CL9) showed ~80% drug release in 8 h and followed Weibull model kinetics. Optimized SLNs (CL10) showed significantly higher permeation (30.45 μg/cm/h; 0.0001) as compared to control (solution). CL10 showed spherical shape and good stability and was found non-irritant for ocular administration. Pharmacokinetics data demonstrated significant improvement of clarithromycin bioavailability ( 0.0001) from CL10, as evidenced by a 150% increase in C (~1066 ng/mL) and a 2.8-fold improvement in AUC (5736 ng h/mL) ( 0.0001) as compared to control solution (C; 655 ng/mL and AUC; 2067 ng h/mL). In summary, the data observed here demonstrate the potential of developed SLNs to improve the ocular permeation and enhance the therapeutic potential of clarithromycin, and hence could be a viable drug delivery approach to treat endophthalmitis.
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http://dx.doi.org/10.3390/pharmaceutics13040523DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8068826PMC
April 2021

Netarsudil: A new ophthalmic drug in the treatment of chronic primary open angle glaucoma and ocular hypertension.

Eur J Ophthalmol 2021 Apr 10:11206721211008783. Epub 2021 Apr 10.

College of Clinical Pharmacy, Department of Pharmaceutical Sciences, King Faisal University, Al-Ahsa, Saudi Arabia.

Background: Vision impairment remains a major health problem worldwide. Elevated intraocular pressure is a prime risk factor for blindness in the elderly. Netarsudil is a Rho-associated protein kinase (ROCK) inhibitor, which also inhibits norepinephrine transport. This narrative review summarizes the properties and clinical significance of netarsudil, a promising drug in topical glaucoma therapy.

Methods: We searched PubMed, Medline and Scopus databases using relevant keywords to retrieve information on the physicochemical properties, formulation, mechanism of action, clinical pharmacokinetics, dose and toxicity of netarsudil.

Results: Netarsudil showed promising effects in lowering the elevated intraocular pressure by two mechanisms. The US FDA approved netarsudil for clinical use in 2017 under the trademark of Rhopressa while European Medicines Agency approved Rhokiinsa in 2019. This drug is available as a 0.02% ophthalmic solution for once-daily topical application.

Conclusion: The discovery of netarsudil is a breakthrough in the therapy of glaucoma with proven efficacy in a wide range of eye pressures and is well tolerated in cases with ocular hypertension and chronic glaucoma.
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http://dx.doi.org/10.1177/11206721211008783DOI Listing
April 2021

Effectiveness of stenting and subsequent re-implantation of disconnected pulmonary artery to restore the pulmonary hemodynamics.

Pediatr Investig 2021 Mar 22;5(1):65-68. Epub 2021 Mar 22.

Pediatric Cardiology team Pediatric Department Faculty of Medicine Taibah University Madinah Saudi Arabia.

Introduction: Early intervention in patients with congenitally disconnected pulmonary artery improves long-term outcome.

Case Presentation: We present 3 cases of isolated disconnected pulmonary artery in the absence of associated structural heart disease during a period of 3 years.

Conclusion: Transcatheter stenting of the feeding ductus arteriosus re-established pulmonary artery flow and growth. Successful surgical repair was achieved, and normal perfusion and complete function of the ipsilateral lung were regained.
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http://dx.doi.org/10.1002/ped4.12251DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7984012PMC
March 2021

Experimental design, formulation and in vivo evaluation of a novel topical in situ gel system to treat ocular infections.

PLoS One 2021 19;16(3):e0248857. Epub 2021 Mar 19.

Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa, Saudi Arabia.

In situ gels have been extensively explored as ocular drug delivery system to enhance bioavailability and efficacy. The objective of present study was to design, formulate and evaluate ion-activated in situ gel to enhance the ocular penetration and therapeutic performance of moxifloxacin in ophthalmic delivery. A simplex lattice design was utilized to examine the effect of various factors on experimental outcomes of the in situ gel system. The influence of polymers (independent variables) such as gellan gum (X1), sodium alginate (X2), and HPMC (X3) on gel strength, adhesive force, viscosity and drug release after 10 h (Q10) were assessed. Selected formulation (MH7) was studied for ex vivo permeation, in vivo irritation and pharmacokinetics in rabbits. Data revealed that increase in concentration of polymers led to higher gel strength, adhesive force and viscosity, however, decreases the drug release. MH7 exhibited all physicochemical properties within acceptable limits and was stable for 6 months. Release profile of moxifloxacin from MH7 was comparable to the check point batches and followed Korsmeyer-Peppas matrix diffusion-controlled mechanism. Ocular irritation study signifies that selected formulation is safe and non-irritant for ophthalmic administration. In vivo pharmacokinetics data indicates significant improvement of moxifloxacin bioavailability (p < 0.0001) from MH7, as evidenced by higher Cmax (727 ± 56 ng/ml) and greater AUC (2881 ± 108 ng h/ml), when compared with commercial eye drops (Cmax; 503 ± 85 ng/ml and AUC; 978 ± 86 ng h/ml). In conclusion, developed in situ gel system (MH7) could offers a more effective and extended ophthalmic therapy of moxifloxacin in ocular infections when compared to conventional eye drops.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0248857PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7978349PMC
March 2021

Influence of tomato waste compost ratios on plant growth and fruit quality of cucumber and summer squash.

J Air Waste Manag Assoc 2021 Mar 23:1-9. Epub 2021 Mar 23.

Department of Agricultural Engineering, College of Food and Agriculture Sciences, King Saud University, Riyadh, Saudi Arabia.

Peat-moss (Sphagnum spp.), is currently an expensive material and a nonrenewable resource with variable properties. Therefore, its use should be gradually reduced. Hence, there are numerous attempts aiming to reduce the use of peat-moss as a bulk substrate and to search for high-quality, locally available and low-cost alternatives to peat-moss. Therefore, the main objective of this research is to investigate the effect of partial replacing of peat-moss with tomato waste compost (TWC) on plant growth, productivity, fruit quality, and morphological features of two types of economic cucurbits species under greenhouse conditions. The plants were planted into pots containing different proportions of TWC (0%, 5%, 10%, 15%, 20% and 30%) with peat-moss, sand and clay as growing substrates. The results indicated that the plant height and the leaves number of both plants were significantly influenced by different substrate treatments. TWC ratios of 15% and 20% increased the amount of cucumber and summer squash fruit yield more than the commercial peat media but they had insignificant differences. Also, they were significantly improved fruit quality characteristics, particularly total soluble solid (TSS) and titratable acidity (TA) of crop fruits more than commercial peat-moss treatment.: Because of the high price of peat-moss and that it is a non-renewable material, farmers resorted to using other alternatives, including green residue compost. Thus, the aim of this work is to reduce the use of peat-moss by replacing it with the use of lokw percentages of TWC. When tomato plant residues return to the soil by converting them into compost, this is a valuable agricultural practice to improve soil fertility and increase the organic matter of the soil as well as increase the source of nitrogen (N) that supports the growth of beneficial microorganisms.
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http://dx.doi.org/10.1080/10962247.2021.1890278DOI Listing
March 2021

Arthroscopic Linked Triple Row Repair for Large and Massive Rotator Cuff Tears.

Arthrosc Tech 2021 Jan 20;10(1):e117-e125. Epub 2021 Jan 20.

Department of Orthopaedic Surgery and Traumatology, Arthroscopy and Sports Injury Unit, Alexandria University, Alexandria, Egypt.

Recently, many arthroscopic techniques have been described to improve the outcomes in rotator cuff repair of large and massive tears; these include conventional double-row, suture bridge, and triple-row techniques, in an effort to optimally reconstruct the rotator cuff footprint and improve fixation. This report describes a modified triple-row repair technique that links the double-row and suture-bridge techniques in one construct, merging the advantages of both to maximize the footprint contact area and contact pressure, which may lead to better healing and faster rehabilitation.
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http://dx.doi.org/10.1016/j.eats.2020.09.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823101PMC
January 2021

Crawford Type IV Congenital Pseudarthrosis of the Tibia: Treatment With Vascularized Fibular Grafting and Outcome at Skeletal Maturity.

J Pediatr Orthop 2021 Mar;41(3):164-170

Department of Orthopedics and Traumatology, Reconstructive Microsurgery Unit, Assiut University Hospitals and School of Medicine, Assiut, Egypt.

Background: Vascularized fibular grafting (VFG) is currently accepted as one of the best treatments for congenital tibial pseudoarthrosis (CPT). However, with longer follow-up, functional results deteriorate, and some problems become evident.

Methods: Thirty-nine patients with CPT were treated with VFG. Their age at surgery averaged 5.2 years. Twenty-one cases aged 3 years or less at the time of surgery. All cases were Crawford type IV affected by neurofibromatosis-1. Fourteen patients had 1 to 7 previous surgeries with an average of 4.2 procedures. The length of the fibula used averaged 9.9 cm, and the fibula was fixed by intramedullary wires in 26 cases, and transfixion screws in 11 cases.

Results: Follow-up averaged 8.1 years. Seventeen cases (43.6%) reached skeletal maturity before the final follow-up. Primary bone union was achieved in 37 cases (96%) after an average of 3.2 months. Stress fracture occurred in 21 cases (51.3%) and was recurrent in 11 cases. Twenty-one cases (53.8%) developed tibial shaft deformities with an average valgus angle of 13.8 degrees and procurvatum angle of 18.8 degrees. The overall final limb length discrepancy (LLD) averaged 2.2 cm. Ipsilateral ankle valgus deformity occurred in 21 cases (53.8%) and averaged 10 degrees. A total of 17 cases required an average of 2 secondary procedures. The tibial deformity did not appear to remodel with age, but the LLD and the angle of ipsilateral ankle valgus deformity continued to significantly increase until skeletal maturity.

Conclusion: This study reports the largest single center experience of CPT cases treated with VFG. Free VFG is an excellent treatment option for CPT. Best results are achieved when the procedure is performed at or before the age of 3 years, in the absence of previous surgeries, and with the use of intramedullary fixation. The resulting LLD and the degree of ipsilateral ankle valgus increase with age until skeletal maturity, however, tibial deformity does not remodel and should be corrected at any age if it is excessive. Donor side mild ankle valgus may occur despite sound tibiofibular synostosis.

Level Of Evidence: Level IV.
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http://dx.doi.org/10.1097/BPO.0000000000001751DOI Listing
March 2021

SARS CoV-2 Organotropism Associated Pathogenic Relationship of Gut-Brain Axis and Illness.

Front Mol Biosci 2020 22;7:606779. Epub 2020 Dec 22.

Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia.

COVID-19 has resulted in a pandemic after its first appearance in a pneumonia patient in China in early December 2019. As per WHO, this global outbreak of novel COVID-19 has resulted in 28,329,790 laboratory-confirmed cases and 911,877 deaths which have been reported from 210 countries as on 12 Sep 2020. The major symptoms at the beginning of COVID-19 are fever (98%), tussis (76%), sore throat (17%), rhinorrhea (2%), chest pain (2%), and myalgia or fatigue (44%). Furthermore, acute respiratory distress syndrome (61.1%), cardiac dysrhythmia (44.4%), shock (30.6%), hemoptysis (5%), stroke (5%), acute cardiac injury (12%), acute kidney injury (36.6%), dermatological symptoms with maculopapular exanthema (36.1%), and death can occur in severe cases. Even though human coronavirus (CoV) is mainly responsible for the infections of the respiratory tract, some studies have shown CoV (in case of Severe Acute Respiratory Syndrome, SARS and Middle East Respiratory Syndrome, MERS) to possess potential to spread to extra-pulmonary organs including the nervous system as well as gastrointestinal tract (GIT). Patients infected with COVID-19 have also shown symptoms associated with neurological and enteric infection like disorders related to smell/taste, loss of appetite, nausea, emesis, diarrhea, and pain in the abdomen. In the present review, we attempt to evaluate the understanding of basic mechanisms involved in clinical manifestations of COVID-19, mainly focusing on interaction of COVID-19 with gut-brain axis. This review combines both biological characteristics of the virus and its clinical manifestations in order to comprehend an insight into the fundamental potential mechanisms of COVID-19 virus infection, and thus endorse in the advancement of prophylactic and treatment strategies.
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http://dx.doi.org/10.3389/fmolb.2020.606779DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7783391PMC
December 2020

Enhancement in antinociceptive and anti-inflammatory effects of tramadol by transdermal proniosome gel.

Asian J Pharm Sci 2020 Nov 19;15(6):786-796. Epub 2019 Jun 19.

College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi Arabia.

Oral therapy of tramadol, an opiate analgesic, undergoes extensive hepatic metabolism and requires frequent administration. Transdermal therapy by virtue can overcome these issues and can improve the efficacy and reduce abuse liability of tramadol. The aim of this research was to investigate the possibility of transdermal delivery of tramadol by formulating proniosome gel and evaluate its therapeutic potential . The effect of formulation composition as well as amount of drug on physicochemical characteristics of prepared proniosomes were examined. Best proniosome gel (F4) was selected and evaluated for drug release, stability and transdermal efficacy by and experiments. The vesicles demonstrated optimal properties including spherical shape, nanosize with good entrapment efficiency, adequate zeta potential, higher stability and greater transdermal flux. The amorphization and dispersion of tramadol in the aqueous core of proniosome vesicles was confirmed by differential scanning calorimeter. Release profile of F4 was distinct ( < 0.001) from control and displayed steady and prolonged tramadol release by Fickian diffusion. Transdermal therapy of F4 showed prominent reduction of induced twitches ( < 0.005) in mice and edema ( < .05) in rats, as compared to oral tramadol. The improvement in clinical efficacy of tramadol in transdermal therapy is correlated with the pharmacokinetic data observed. In conclusion, the observed improvement in antinociceptive and anti-inflammatory effects from proniosome carriers signifies its potential to be a suitable alternative to oral therapy of tramadol with greater efficacy.
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http://dx.doi.org/10.1016/j.ajps.2019.05.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7750831PMC
November 2020

Mechanisms of Antidiabetic Activity of Methanolic Extract of Leaves in Nicotinamide/Streptozotocin-Induced Type 2 Diabetes in Rats.

Plants (Basel) 2020 Nov 19;9(11). Epub 2020 Nov 19.

Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi Arabia.

The current study aimed to establish the mechanisms of antidiabetic activity of methanolic extract of leaves (MEPGL) in nicotinamide/streptozotocin-induced type 2 diabetes in rats. Phytochemical screening, HPLC analysis, and acute toxicity study of MEPGL were carried out. Various concentrations of MEPGL (100, 200, 400, and 600 mg/kg) were administered orally to diabetic rats for 45 days on a daily basis. The antidiabetic effect of MEPGL was examined by measuring blood glucose, plasma insulin, and glycated hemoglobin (HbA1c) levels, as well as with an oral glucose tolerance test. The antioxidant effect of MEPGL was determined by analyzing hepatic and renal antioxidant markers, namely superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH), and lipid peroxidation. The other biochemical markers alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), urea, and creatinine, as well as total cholesterol, triglycerides, and high-density lipoprotein (HDL) were also studied. Type 2 diabetes significantly altered these parameters, while oral administration of the MEPGL significantly ameliorated them. Moreover, the pancreatic histopathological changes were attenuated with MEPGL treatment. In a nutshell, oral MEPGL administration in diabetic rats showed antidiabetic activity due to its antioxidant activity, most probably due to the gallic acid, ellagic acid, and apigenin found in MEPGL.
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http://dx.doi.org/10.3390/plants9111609DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7699557PMC
November 2020

Anomalous Drainage of Persistent Left Superior Vena Cava to the Left Atrium: Case Series and Literature Review.

J Saudi Heart Assoc 2020 15;32(2):190-193. Epub 2020 Jul 15.

Medina Cardiac Center, Saudi Arabia.

Persistent left superior vena cava (PLSVC) draining into the coronary sinus is not uncommon, but to the left atrium is a rare condition. Such anomaly may be a cause of unexplained hypoxia in all age groups. It is often diagnosed accidentally during cardiovascular diagnostic work-up or in a contest of other cardiac investigations. We report two cases of these rare PLSVC associations with subsequent medical and surgical management.
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http://dx.doi.org/10.37616/2212-5043.331DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7640547PMC
July 2020

4-Aryl-1,4-Dihydropyridines as Potential Enoyl-Acyl Carrier Protein Reductase Inhibitors: Antitubercular Activity and Molecular Docking Study.

Curr Top Med Chem 2021 ;21(4):295-306

Department of Biotechnology and Food Technology, Durban University of Technology, Durban 4001, South Africa.

Background: Tuberculosis remains one of the most deadly infectious diseases worldwide due to the emergence of multi-drug resistance (MDR) and extensively drug resistance (XDR) strains of Mycobacterium tuberculosis (MTB).

Aims: Currently, available drugs are getting resistant and toxic. Hence, there is an urgent need for the development of potent molecules to treat tuberculosis.

Materials And Methods: Herein, the screening of a total of eight symmetrical 1,4-dihydropyridine (1,4- DHP) derivatives (4a-4h) was carried out for whole-cell anti-TB activity against the susceptible H37Rv and MDR strains of MTB.

Results And Discussion: Most of the compounds exhibited moderate to excellent activity against the susceptible H37Rv. Moreover, the most promising compound 4f (against H37Rv) having paratrifluoromethyl phenyl group at 4-position and bis para-methoxy benzyl ester group at 3- and 5- positions of 1,4-dihydropyridine pharmacophore, exhibited no toxicity, but demonstrated weak activity against MTB strains resistant to isoniazid and rifampicin. In light of the inhibitory profile of the title compounds, enoyl-acyl carrier protein reductase (InhA) appeared to be the appropriate molecular target. A docking study of these derivatives against InhA receptor revealed favorable binding interactions. Further, in silico predicted ADME properties of these compounds 4a-4h were found to be in the acceptable ranges, including satisfactory Lipinski's rule of five, thereby indicating their potential as drug-like molecules.

Conclusion: In particular, the 1,4-DHP derivative 4f can be considered an attractive lead molecule for further exploration and development of more potent anti-TB agents as InhA inhibitors.
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http://dx.doi.org/10.2174/1568026620666201102121606DOI Listing
January 2021

The efficacy and safety of percutaneous balloon angioplasty for aortic coarctation in children. Acute and mid-term results in a single center experience.

Saudi Med J 2020 Nov;41(11):1252-1258

Department of Pediatrics, Faculty of Medicine, Taibah University, Madinah, Kingdom of Saudi Arabia. E-mail.

Objectives: To assess the efficacy and safety of balloon angioplasty (BAP) procedure for treatment of coarctation of the aorta (CoA) in children. Methods: A retrospective study included 27 consecutive children, underwent BAP for either native-CoA (Na-CoA) or recoarctation (Re-CoA). Medical records, echocardiographic findings, angiographic and hemodynamic data were collected from the hospital database. Follow‑up was scheduled at 1, 3, 6, 12 months after the procedure. The study took place over a period of 4.5 years, from April 2014 to January 2019, in Madinah Cardiac Center, Madinah, Northwest region, Saudi Arabia.

Results: The mean age of patients was 11.86±8.96 months. Seven children had Na-CoA and 20 children had Re-CoA. The success rate of the procedure was achieved in 23 children (85%), as BAP reduced the mean systolic pressure gradient across the CoA (Na-CoA: from 45.28± 18.3 to 9.8± 6.57 mm Hg, p=0.0009), and in Re-CoA groups (from 42.48±16.7 to 10.9±8.5 mm Hg, p less than 0.0001). In mid-term follow-up, the need for re-intervention occurred in 8 children of the cohort (3 children [42.8%] from the Na-CoA group, and 5 children [25%] from the Re-CoA group).  Conclusions: Balloon angioplasty is considered a safe procedure for the management of CoA, but its efficacy remains questionable especially for young infants with Na-CoA type. However, it is a reliable option for managing Re-CoA children, with a lower rate of future re-intervention.
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http://dx.doi.org/10.15537/smj.2020.11.25452DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7804232PMC
November 2020

Development of HPLC Method for Quantification of Sinigrin from Roots and Evaluation of Its Anticancer Potential.

Molecules 2020 Oct 26;25(21). Epub 2020 Oct 26.

Department of Pharmaceutics, Institute of Pharmacy, Nirma University, Ahmedabad 382481, Gujarat, India.

Sinigrin, a precursor of allyl isothiocyanate, present in the exhibits diverse biological activities, and has an immense role against cancer proliferation. Therefore, the objective of this study was to quantify the sinigrin in the roots using developed and validated RP-HPLC method and further evaluated its' anticancer activity. To achieve the objective, the roots of were lyophilized to obtain a stable powder, which were extracted and passed through an ion-exchange column to obtain sinigrin-rich fraction. The RP-HPLC method using C18 analytical column was used for chromatographic separation and quantification of sinigrin in the prepared fraction, which was attained using the mobile phase consisting of 20 mM tetrabutylammonium: acetonitrile (80:20%, / at pH 7.0) at a flow rate of 0.5 mL/min. The chromatographic peak for sinigrin was showed at 3.592 min for pure sinigrin, where a good linearity was achieved within the concentration range of 50 to 800 µg/mL ( > 0.99), with an excellent accuracy (-1.37% and -1.29%) and precision (1.43% and 0.94%), for intra and inter-day, respectively. Finally, the MTT assay was performed for the sinigrin-rich fraction using three different human cancer cell lines, viz. prostate cancer (DU-145), colon adenocarcinoma (HCT-15), and melanoma (A-375). The cell-based assays were extended to conduct apoptotic and caspase-3 activities, to determine the mechanism of action of sinigrin in the treatment of cancer. MTT assay showed values of 15.88, 21.42, and 24.58 µg/mL for DU-145, HCT-15, and A-375 cell lines, respectively. Increased cellular apoptosis and caspase-3 expression were observed with sinigrin-rich fraction, indicating significant increase in overexpression of caspase-3 in DU-145 cells. In conclusion, a simple, sensitive, fast, and accurate RP-HPLC method was developed for the estimation of sinigrin in the prepared fraction. The data observed here indicate that sinigrin can be beneficial in treating prostate cancer possibly by inducing apoptosis.
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http://dx.doi.org/10.3390/molecules25214947DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7663242PMC
October 2020

The Beneficial Effect of Boswellic Acid on Bone Metabolism and Possible Mechanisms of Action in Experimental Osteoporosis.

Nutrients 2020 Oct 18;12(10). Epub 2020 Oct 18.

Department of Pharmaceutics, Institute of Pharmacy, Nirma University, Ahmedabad 382481, Gujarat, India.

Estrogen is instrumental in the pathological process of osteoporosis because a deficiency of this hormone increases the release of bone-resorbing cytokines. Acetyl-11-keto-β-boswellic acid (AKBA), a constituent from , has an anti-inflammatory effect by inhibiting tumor necrosis factor-α (TNF-α) expression, which leads to a decline in receptor activator of nuclear factor-kappa B (NF-κB) ligand, and consequently, a reduction in osteoclast activity. Hence, AKBA may be beneficial against bone loss during osteoporosis. Therefore, the current study intended to evaluate the beneficial effects of AKBA in ovariectomy-induced osteoporosis and to investigate its mechanism of action. Sham-operation or ovariectomy female Sprague Dawley rats were used for evaluating the antiosteoporotic effect of AKBA in this study. AKBA (35 mg/kg, p.o.) and estradiol (0.05 mg/kg, i.m.) were administered for 42 days. At the end of the experiment, body and uterus weights, serum and urine calcium and phosphorus, serum alkaline phosphatase, and urinary creatinine levels, besides serum levels of NF-κB and TNF-α were determined. Weight, length, thickness, hardness, calcium content, as well as the bone mineral density of femur bone and lumbar vertebra were measured. A histopathological examination was also carried out. AKBA ameliorated all tested parameters and restored a normal histological structure. Thus, AKBA showed good antiosteoporotic activity, which may be mediated through its suppression of the NF-κB-induced TNF-α signaling pathway.
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http://dx.doi.org/10.3390/nu12103186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7603128PMC
October 2020

Transcatheter device closure of ventricular septal defects in children: a retrospective study at a single cardiac center.

Ann Saudi Med 2020 Sep-Oct;40(5):396-402. Epub 2020 Oct 1.

From the Department of Pediatrics, Faculty of Medicine, Mansoura University, Mansoura, Egypt.

Background: Ventricular septal defect (VSD) is the most common congenital heart disease in the pediatric population. Nowadays, trans-catheter closure is considered a feasible method of therapy for most muscular and some perimembranous types of VSDs.

Objective: Assess the safety, efficacy and outcome of percutaneous transcatheter closure of VSDs in children.

Design: Retrospective, single center study.

Setting: Madinah Cardiac Center, Madinah, Saudi Arabia.

Patients And Methods: The study included all consecutive children who underwent transcatheter closure of isolated VSD during the period from December 2014 to January 2019. The data were collected from hospital database medical records. Transthoracic echocardiography (TTE) and an electrocardiogram (ECG) were done before and after the procedure in all the patients. The device was implanted by the retrograde or antegrade approach. All patients were subjected to follow-up evaluation at 1, 3, 6, 12 months, and annually thereafter with TTE and ECG.

Main Outcome Measures: Procedure success rate, clinical follow-up, TTE.

Sample Size: 70 children.

Results: The mean (standard deviation) age of patients was 10.2 (4.1) years (range: 2-18 years), and their mean body weight was 30.9 (13.9) kg (range: 7.0-57.7 kg). Forty-eight (68.6%) children had muscular VSD (mVSD), and 22 (31.4%) children had perimembranous VSD (pmVSD). The majority of defects were closed via the retrograde approach using the Amplatzer muscular occluder device. At 24 hours after the procedure, the success rate was 90%. Only four (5.7%) cases had major adverse events including complete atrioventricular block, hemolysis, and thrombus formation.

Conclusion: Transcatheter closure is a safe and feasible procedure in VSDs of various morphologies, with a low adverse event rate.

Limitations: Retrospective design, single-center study, absence of control group.

Conflict Of Interest: None.
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http://dx.doi.org/10.5144/0256-4947.2020.396DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7532053PMC
October 2020

Outcomes of the Star Repair for Large and Massive Rotator Cuff Tears: A Modified Triple-Row Technique.

Orthop J Sports Med 2020 Sep 15;8(9):2325967120952998. Epub 2020 Sep 15.

Department of Orthopaedic Surgery and Traumatology, Alexandria Arthroscopy and Sports Injury Unit, Alexandria University, Egypt.

Background: Large and massive rotator cuff repairs constitute a true challenge for arthroscopic shoulder surgeons. Retear rates as high as 20% have been reported after arthroscopic double-row and suture-bridge techniques used for these tears.

Hypothesis: A modified triple-row repair will provide satisfactory clinical results with lower risk for retear.

Study Design: Case series; Level of evidence, 4.

Methods: Between March 2016 and August 2017, a total of 52 patients with large and massive rotator cuff tears received a modified triple-row cuff repair. A middle repositioning anchor was inserted between the medial and the lateral rows. The middle anchor sutures were loaded to lateral knotless anchors in a star-shaped configuration. Functional evaluation was performed using the American Shoulder and Elbow Surgeons score, University of California, Los Angeles score, Constant-Murley score, and Simple Shoulder Test. Subjective evaluation was carried out using a visual analog scale for pain and a subjective shoulder value score. Health-related as well as disease-specific quality-of-life scores were also used. Retear rates were assessed by means of musculoskeletal ultrasonography. Patients were evaluated for a minimum of 24 months.

Results: This study included 34 female and 18 male patients with a mean age of 57.17 ± 6.7 years. There were 35 patients (67.3%) with large tears and 17 patients (32.7%) with massive tears. Significant improvement from preoperative values was seen in all functional and subjective scores ( < .001). The mean forward flexion was 163° ± 9.7°, and the mean lateral abduction was 159.4° ± 9.4°. All patients had excellent scores on the general health-related and disease-specific quality-of-life scales. No retears were reported at the end of the follow-up period.

Conclusion: The star-shaped, modified triple-row cuff repair is a valid and effective solution for surgical management of large and massive rotator cuff tears, providing excellent results and low risk for retears.
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http://dx.doi.org/10.1177/2325967120952998DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7495945PMC
September 2020

The trends and patterns of congenital heart diseases at Madinah Cardiac Center, Madinah, Saudi Arabia.

Saudi Med J 2020 Sep;41(9):977-983

Department of Pathology, Faculty of Medicine, Taibah University, Al-Madinah Al-Munawwarah, Kingdom of Saudi Arabia. E-mail.

Objectives: To characterize the pattern of congenital heart diseases (CHDs) in Madinah, Saudi Arabia.

Methods: We retrospectively collected and analyzed the demographic and diagnostic details of all patients with CHDs referred at Madinah Cardiac Center (MCC) over a period of 3 years from January 2017 to December 2019.

Results: During the study period, 1,127 patients with CHDs were identified. The male to female ratio was 1.1:1, with a mean age of 8.4±2.4 years. The acyanotic CHDs were the predominant lesions, accounting for 84.8% of all cases, while the cyanotic types accounted for 13%. Patent ductus arteriosus (PDA), ventricular  septal defects (VSD), atrial septal defects (ASD), coarctation of the aorta (CoA), and atrioventricular septal defect (AVSD) were the most common acyanotic CHDs and represented 27.9%, 24.8%, 18.9%, 6.4%, and 4.4% of the total cases, respectively. Tetralogy of Fallot (ToF) (8.7%), followed by transposition of the great arteries (TGA) (1.7%) and truncus arteriosus (1.1%), were the most common cyanotic CHDs. There was a male predominance of VSD, ToF, CoA, TGA, and truncus arteriosus. In contrast, PDA, ASD, and AVSD were more common in females.  Conclusion: The pattern of CHDs observed in our study and age at which the diagnosis of CHDs was made were different from the other national and international studies, which points to a diagnostic issue along with problems of awareness on the part of the general population.
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http://dx.doi.org/10.15537/smj.2020.9.25275DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7557563PMC
September 2020

The Possible Contribution of P-Glycoprotein in the Protective Effect of Paeonol against Methotrexate-Induced Testicular Injury in Rats.

Pharmaceuticals (Basel) 2020 Aug 29;13(9). Epub 2020 Aug 29.

Department of Pharmacology, Faculty of Medicine, Minia University, El-Minia 61511, Egypt.

Paeonol, a phenolic ingredient in the genus , possesses antioxidant and anti-inflammatory effects. Methotrexate (MTX) is a commonly used chemotherapeutic agent; however, its germ cell damage is a critical problem. P-glycoprotein (P-gp), an efflux transporter, is a member of the blood-testis barrier. The present study evaluated the protective effect of paeonol on MTX-induced testicular injury in rats with the exploration of its mechanism and the possible contribution of P-gp in such protection. Testicular weight, serum testosterone, and testicular P-gp levels were measured. Testicular oxidant/antioxidant status was evaluated via determining the levels of malondialdehyde, total nitrite, reduced glutathione, and superoxide dismutase activity. The inflammatory cytokine tumor necrosis factor-alpha (TNF-α) and the apoptotic marker caspase 3 were estimated immunohistochemically. Testicular histopathology and spermatogenesis scores were also examined. MTX caused histopathologically evident testicular damage with decreased testicular weight, testosterone level, and spermatogenesis score, as well as significant increases in oxidative, inflammatory, and apoptotic responses. Paeonol significantly restored testicular weight, testosterone level, spermatogenesis score, and oxidant/antioxidant balance. Moreover, paeonol increased the testicular P-gp level and significantly decreased TNF-α and caspase 3 immunostaining. In conclusion, paeonol offered a protective effect against MTX-induced testicular injury through its antioxidant, anti-inflammatory, and antiapoptotic effects, as well as by increasing testicular P-gp level.
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http://dx.doi.org/10.3390/ph13090223DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7558391PMC
August 2020

Arthroscopic Shoulder Fusion for Obstetric Brachial Plexus Palsy.

Arthrosc Tech 2020 Jul 1;9(7):e1049-e1055. Epub 2020 Jul 1.

Department of Orthopaedic Surgery and Traumatology, Arthroscopy and Sports Injury Unit, Alexandria University, Alexandria.

Shoulder fusion for sequelae of obstetrical brachial plexus injury is reported as a valuable surgical solution with very good results and functional range of motion. It is traditionally performed in open fashion. Few reports describe the technique of arthroscopic shoulder fusion, but nearly all of them were done in cases with traumatic brachial plexus injury that have normal joint anatomy. This report describes and discusses the arthroscopic shoulder fusion technique in cases with disorganized glenohumeral joint secondary to obstetric brachial plexus injury. An illustrative case example is presented.
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http://dx.doi.org/10.1016/j.eats.2020.03.025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7372597PMC
July 2020

Taurine prevents high-fat diet-induced-hepatic steatosis in rats by direct inhibition of hepatic sterol regulatory element-binding proteins and activation of AMPK.

Clin Exp Pharmacol Physiol 2020 Jul 21. Epub 2020 Jul 21.

Department of Obstetrics and Gynecology, College of Medicine, King Khalid University, Abha, Saudi Arabia.

This study investigated if the protective effect of taurine against high fat diet-induced hepatic steatosis involves modulating the hepatic activity of 5' AMP-activated protein kinase (AMPK) and levels/activity of the sterol regulatory element-binding proteins-1/2 (SREBP1/2). Rats were divided into four groups (n = 12/group) as (a) STD, fed standard diet (3.85 kcal/g); (b) STD + taurine (500 mg/kg); (c) HFD, fed HFD (4.73 kcal/g); and (d) HFD + taurine. All treatments were conducted for 12 weeks. Independent of food intake or modulating glucose or insulin levels, taurine administration to STD and HFD-fed rats significantly lowered weekly weight gain and the accumulation of the retroperitoneal, visceral and subcutaneous fats. In both groups, taurine also reduced serum and hepatic levels of triglycerides and cholesterol and reduced hepatic mRNA and protein levels of fatty acid synthase (FAS), acetyl CoA carboxylase-1 (ACC-1), HMG-CoA-reductase and HMG-CoA synthetase. In control rats only, taurine reduced hepatic levels of mature forms of sterol regulatory element-binding proteins (SREBP)-1/2. In HFD-fed rats, taurine reduced SREBP-1/2 precursor and mature forms in the livers of HFD-fed rats. Besides, taurine significantly increased levels of glutathione (GSH), the activity of superoxide dismutase (SOD), and the activity of AMPK and its downstream β-oxidation genes including peroxisome proliferator-activated receptor-α (PPAR-α) and carnitine palmitoyltransferase (CPT-1) in the livers of both the control and HFD-fed rats. In conclusion, taurine protects against HFD-induced hepatic steatosis stimulating antioxidant levels, and concomitant stimulating hepatic β-oxidation and suppressing lipid synthesis, mediated by activation of AMPK and suppression of SREBP-1.
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http://dx.doi.org/10.1111/1440-1681.13387DOI Listing
July 2020

COVID-19. An update for orthopedic surgeons.

SICOT J 2020 1;6:24. Epub 2020 Jul 1.

Orthopedic Department, Assiut University Hospitals, Assiut 71515, Egypt - Spine center, Helios Klinikum Erfurt, Nordhaeuser street 74, 88089 Erfurt, Germany.

The COVID-19 pandemic has affected our world in a short period of time, and the orthopedic surgery practice was not an exclusion. Elective care was deferred in most health care facilities and emergency care was continued with strict precautions. With rapid progression of the pandemic, the response of the medical community is also rapidly changing in all aspects of delivering care. This led to a large number of publications with reports, guidelines, measures, ways to react to the crisis, and post-pandemic predictions and speculations. In this review we aimed at summarizing all the relevant information to the orthopedic surgery community. To do this, a comprehensive search was performed with all related terms on two scientific search engines, PubMed and SCOPUS, and the results were filtered by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method. The result was 72 articles that were further reduced to 33 articles after full text reading. The resultant information was organized under 5 main headings; the impact of pandemic on the orthopedic practice, COVID-19 and the trauma patient, elective and emergency surgeries during the pandemic, peri-operative management of the patient with COVID-19, Miscellaneous effects of the pandemic such as those on training programs and the evolution of telemedicine. This review represents the most up to date information published in the literature that is a must-know to every orthopedic surgeon.
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http://dx.doi.org/10.1051/sicotj/2020022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7328530PMC
July 2020

Repurposing of FDA-approved antivirals, antibiotics, anthelmintics, antioxidants, and cell protectives against SARS-CoV-2 papain-like protease.

J Biomol Struct Dyn 2020 Jun 29:1-8. Epub 2020 Jun 29.

Computational Chemistry Laboratory, Chemistry Department, Faculty of Science, Minia University, Minia, Egypt.

SARS-CoV-2 or Coronavirus disease 19 (COVID-19) is a rapidly spreading, highly contagious, and sometimes fatal disease for which drug discovery and vaccine development are critical. SARS-CoV-2 papain-like protease (PL) was used to virtually screen 1697 clinical FDA-approved drugs. Among the top results expected to bind with SARS-CoV-2 PL strongly were three cell protectives and antioxidants (NAD+, quercitrin, and oxiglutatione), three antivirals (ritonavir, moroxydine, and zanamivir), two antimicrobials (doripenem and sulfaguanidine), two anticancer drugs, three benzimidazole anthelmintics, one antacid (famotidine), three anti-hypertensive ACE receptor blockers (candesartan, losartan, and valsartan) and other miscellaneous systemically or topically acting drugs. The binding patterns of these drugs were superior to the previously identified SARS CoV PL inhibitor, 6-mercaptopurine (6-MP), suggesting a potential for repurposing these drugs to treat COVID-19. The objective of drug repurposing is the rapid relocation of safe and approved drugs by bypassing the lengthy pharmacokinetic, toxicity, and preclinical phases. The ten drugs with the highest estimated docking scores with favorable pharmacokinetics were subjected to molecular dynamics (MD) simulations followed by molecular mechanics/generalized Born surface area (MM/GBSA) binding energy calculations. Phenformin, quercetin, and ritonavir all demonstrated prospective binding affinities for COVID-19 PL over 50 ns MD simulations, with binding energy values of -56.6, -40.9, and -37.6 kcal/mol, respectively. Energetic and structural analyses showed phenformin was more stable than quercetin and ritonavir. The list of the drugs provided herein constitutes a primer for clinical application in COVID-19 patients and guidance for further antiviral studies.Communicated by Ramaswamy H. Sarma.
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http://dx.doi.org/10.1080/07391102.2020.1784291DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7332862PMC
June 2020

Crystallography, in Silico Studies, and In Vitro Antifungal Studies of 2,4,5 Trisubstituted 1,2,3-Triazole Analogues.

Antibiotics (Basel) 2020 Jun 20;9(6). Epub 2020 Jun 20.

Department of Biotechnology and Food Technology, Durban University of Technology, Durban 4001, South Africa.

A series of 2,4,5 trisubstituted-1,2,3-triazole analogues have been screened for their antifungal activity against five fungal strains, , , , , and , via a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) microdilution assay. Compounds GKV10, GKV11, and GKV15 emerged as promising antifungal agents against all the fungal strains used in the current study. One of the highly active antifungal compounds, GKV10, was selected for a single-crystal X-ray diffraction analysis to unequivocally establish its molecular structure, conformation, and to understand the presence of different intermolecular interactions in its crystal lattice. A cooperative synergy of the C-H···O, C-H···N, C-H···S, C-H···π, and π···π intermolecular interactions was present in the crystal structure, which contributed towards the overall stabilization of the lattice. A molecular docking study was conducted for all the test compounds against lanosterol-14α-demethylase (pdb = 5 tzl). The binding stability of the highly promising antifungal test compound, GKV15, from the series was then evaluated by molecular dynamics studies.
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http://dx.doi.org/10.3390/antibiotics9060350DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7344790PMC
June 2020

Effect of on TGF-β1 and vascular mediators in a rat model of diabetic nephropathy.

Arch Physiol Biochem 2020 Jun 23:1-11. Epub 2020 Jun 23.

Medical Physiology Department, College of Medicine, Khartoum University, Khartoum, Sudan.

Transforming growth factor-β1 (TGF-β1), endothelin-1 and angiotensin II are responsible for extracellular matrix accumulation within the kidney in diabetic nephropathy. This study evaluated the effect of adding Gum Arabic (GA) and insulin on serum glucose, renal function, TGF-β1, endothelin-1, and angiotensin II in rats with diabetic nephropathy. Sixty male Sprague-Dawley rats were divided into; normal, normal plus GA, diabetic rats (DM), DM plus insulin, DM plus GA, and DM plus insulin plus GA groups. Levels of glucose and creatinine in serum, TGF-β1, angiotensin II, and endothelin-1 in renal homogenate and HbA1c were measured. Serum creatinine, TGF-β1, angiotensin II, and endothelin-1 were increased in diabetic rats. GA decreased serum glucose, TGF-β1, angiotensin II, endothelin-1, and HbA1c in diabetic rats. GA and insulin decreased serum glucose, creatinine, TGF-β1, angiotensin II, endothelin-1, and HbA1c in diabetic rats. Co-administration of GA with insulin to rats with diabetic nephropathy improved the glycemic state, renal function, TGF-β1, endothelin-1, and angiotensin II.
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http://dx.doi.org/10.1080/13813455.2020.1781901DOI Listing
June 2020

In silico and in vitro identification of secoisolariciresinol as a re-sensitizer of P-glycoprotein-dependent doxorubicin-resistance NCI/ADR-RES cancer cells.

PeerJ 2020 10;8:e9163. Epub 2020 Jun 10.

Department of Biomedical Sciences/College of Veterinary Medicine, King Faisal University, Al-Ahsa, Eastern Region, Saudi Arabia.

P-glycoprotein (P-gp) is one of the highly expressed cancer cell efflux transporters that cause the failure of chemotherapy. To reverse P-gp induced multidrug resistance, we employed a flaxseed-derived lignan; secoisolariciresinol (SECO) that acts as an inhibitor of breast cancer resistance protein; another efflux transporter that shares some substrate/inhibitor specificity with P-gp. Molecular dynamics (MD) simulation identified SECO as a possible P-gp inhibitor. Comparing root mean square deviation (RMSD) of P-gp bound with SECO with that bound to its standard inhibitor verapamil showed that fluctuations in RMSD were lower in P-gp bound to SECO demonstrating higher stability of the complex of P-gp with SECO. In addition, the superimposition of P-gp structures after MD simulation showed that the nucleotide-binding domains of P-gp bound to SECO undertook a more central closer position compared with that bound to verapamil. Using rhodamine efflux assay on NCI/ADR-RES cancer cells, SECO was confirmed as a P-gp inhibitor, where cells treated with 25 or 50 µM of SECO showed significantly higher fluorescence intensity compared to control. Using MTT assay, SECO alone showed dose-dependent cytotoxicity, where 25 or 50 µM of SECO caused significantly less NCI/ADR-RES cellular viability compared to control. Furthermore, when 50 µM of SECO was added to doxorubicin (DOX), an anticancer drug, SECO significantly enhanced DOX-induced cytotoxicity compared to DOX alone. The combination index calculated by CompuSyn software indicated synergism between DOX and SECO. Our results suggest SECO as a novel P-gp inhibitor that can re-sensitize cancer cells during DOX chemotherapy.
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http://dx.doi.org/10.7717/peerj.9163DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7293189PMC
June 2020

Moran and Morsy reply to Dr Xiong.

J Hand Surg Am 2020 08 14;45(8):e9. Epub 2020 Jun 14.

Department of Orthopedics Assiut University Hospital, Assiut, Egypt.

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http://dx.doi.org/10.1016/j.jhsa.2020.04.015DOI Listing
August 2020

Cytotoxicity and Antimycobacterial Properties of Pyrrolo[1,2-]quinoline Derivatives: Molecular Target Identification and Molecular Docking Studies.

Antibiotics (Basel) 2020 May 7;9(5). Epub 2020 May 7.

Department of Chemistry, School of Basic Science, Rani Channamma University, Belagavi 591156, India.

A series of ethyl 1-(substituted benzoyl)-5-methylpyrrolo[1,2-]quinoline-3-carboxylates - and dimethyl 1-(substituted benzoyl)-5-methylpyrrolo[1,2-]quinoline-2,3-dicarboxylates - have been synthesized and evaluated for their anti-tubercular (TB) activities against H37Rv (American Type Culture Collection (ATCC) strain 25177) and multidrug-resistant (MDR) strains of by resazurin microplate assay (REMA). Molecular target identification for these compounds was also carried out by a computational approach. All test compounds exhibited anti-tuberculosis (TB) activity in the range of 8-128 µg/mL against H37Rv. The test compound dimethyl-1-(4-fluorobenzoyl)-5-methylpyrrolo[1,2-]quinoline-2,3-dicarboxylate emerged as the most promising anti-TB agent against H37Rv and multidrug-resistant strains of at 8 and 16 µg/mL, respectively. In silico evaluation of pharmacokinetic properties indicated overall drug-likeness for most of the compounds. Docking studies were also carried out to investigate the binding affinities as well as interactions of these compounds with the target proteins.
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http://dx.doi.org/10.3390/antibiotics9050233DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7277568PMC
May 2020