Publications by authors named "M Y Mubarak"

373 Publications

Evaluation of transverse dorsal lumbotomy in management of PUJ obstruction in patients younger than 6 months.

Urologia 2021 Feb 14:391560321993600. Epub 2021 Feb 14.

Department of Surgery, Salmaniya Medical Complex, Manama, Kingdom of Bahrain.

Objective: The transverse dorsal lumbotomy approach provides excellent exposure to the PUJ and causes minimal tissue damage. In this study, we assess the efficacy of dorsal lumbotomy in PUJ obstruction in children younger than 6 months.

Methods: All children less than 6 months who were managed with the dorsal lumbotomy approach between 2009 and 2017 were reviewed prospectively. Data included: demographic data, pre/post-operative renal ultrasound scan with SFU grading and RDS, operative time, post-operative complications, and follow up results.

Results: A total of 42 children with a mean age of 4.4 ± 1 months were included. On pre-operative RDS, all patients had an obstructive pattern and a SRF of 30.3 ± 9.3. The mean operative duration was 49 min and analgesia was minimal. Post-operative ultrasound at 6 months showed an improvement in hydronephrosis ( < 0.05) and a mean SRF of 39.3 ± 6.1 ( < 0.001).

Conclusion: Transverse dorsal lumbotomy approach is a safe and efficient alternative in patients less than 6 month.
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http://dx.doi.org/10.1177/0391560321993600DOI Listing
February 2021

From Digital to Computational Pathology and Integrated Diagnostics: The Future of Histopathology.

Authors:
Muhammed Mubarak

J Coll Physicians Surg Pak 2021 Jan;31(1):2-3

Department of Histopathology, Sindh Institute of Urology and Transplantation (SIUT), Karachi, Pakistan.

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http://dx.doi.org/10.29271/jcpsp.2021.01.2DOI Listing
January 2021

Improved of growth and phytostabilization potential of lead (Pb) in L. under the effect of IAA and GA alone and in combination with EDTA by altering biochemical attributes of stressed plants.

Int J Phytoremediation 2021 Jan 18:1-11. Epub 2021 Jan 18.

Department of Botany and Microbiology, Faculty of Science, Damanhour University, Damanhour, Egypt.

This study evaluated the effect of EDTA, IAA and GA alone and in combination in improving plant growth, Pb accumulation, and management of effective mechanisms associated with alleviation of Pb-induced adverse effect in L. grown on industrial area in Alexandria. In this regards, 10-week-old plants were subjected to IAA and GA as a foliar spray and EDTA was supplied in two doses 50 and 200mgkg soil. EDTA significantly reduced the plant growth and dry biomass, whereas GA and IAA foliar spray increased growth significantly when compared with control (uncontaminated soil). In combined treatments of EDTA + GA +IAA, the biomass was restored, which shows that GA and IAA did compensate the negative effect of EDTA on plant growth and increased the Pb uptake significantly into roots. There were high GSH contents parallel with the increase of glutathione-S-transferase activity and induction of the antioxidant enzymes (SOD, CAT, APX, GR) as well as oxidized glutathione and ascorbic acid contents in leaves and roots when compared to control plants. This study suggests that is promising species for decontamination of Pb -contaminated soil and the application of EDTA together with IAA and GA could be a useful strategy for enhancing the phytostabilization capability of L. to eliminate Pb from contaminated soils. : The objective of this paper is to investigate the physiological performance of as a new native for phytoremediation by phytostabilization mechanism of Pb after treatment with EDTA and phytohormones. Chemical additives of EDTA and GA as well as IAA are promising alternatives to provide added benefits due to their individual credentials in improving the overall phytostabilization effectiveness and better immobilization efficiency in treating Pb contaminated soils by altering biochemical attributes of stressed plants. Currently these additives are not employed widely in large-scale field implementations, so field applications of these additives using are essential for Phytoremediation of Pb-contaminated soils.
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http://dx.doi.org/10.1080/15226514.2020.1870928DOI Listing
January 2021

Evaluation of the Binding Affinity of Anti-Viral Drugs against Main Protease of SARS-CoV-2 through a Molecular Docking Study.

Infect Disord Drug Targets 2020 Dec 7. Epub 2020 Dec 7.

Department of Chemistry, The University of Jordan, Amman 11942. Jordan.

Background: Coronavirus disease 2019 (COVID-19) is a life intimidating viral infection caused by a positive sense RNA virus belonging to the Coronaviridae family, named severe acute respiratory distress syndrome coronavirus 2 (SARA-CoV-2). Since its outbreak in December 2019, the pandemic has spread to more than 200 countries, infected more than 26 million, and claimed the lives of more than 800,000 people. As a disease, COVID-19 can lead to severe and occasionally fatal respiratory problems in humans. Infection with this virus is associated with fever, cough, dyspnea, and muscle aches, and it may progress to pneumonia, multiple organ failure, and death. To date, there is no specific antiviral treatment against this virus. However, the main viral protease has been recently discovered and it is regarded as an appropriate target for antiviral agents in the search for treatment of COVID-19, due to its pivotal role in polyproteins processing during viral replication.

Aim: Consequently, this study intends to evaluate the effectiveness of FDA-approved anti-viral drugs against SARA-CoV-2 through a molecular docking study.

Methods: AutoDock Vina in PyRx platform was used for docking analysis against the main viral protease (Mpro) (PDB ID 6LU7), and Computed Atlas of Surface Topography of proteins (CASTp 3.0) was applied for detecting and characterizing cavities, pockets, and channels of this protein structure.

Results: Results revealed that among the conventional antiviral drugs, the protease inhibitors, lopinavir, amprenavir, indinavir, maraviroc, saquinavir, and daclatasvir showed high binding affinity and interacted with amino acid residues of the binding site.

Conclusion: In conclusion, protease inhibitors may be effective potential antiviral agents against Mpro to combat SARSCoV-2.
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http://dx.doi.org/10.2174/1871526520666201207124408DOI Listing
December 2020

The positive impact of social media on the level of COVID-19 awareness in Saudi Arabia: a web-based cross-sectional survey.

Infez Med 2020 12;28(4):545-550

Department of Pediatric, Maternal and Children Hospital, Alahsa, Saudi Arabia.

In late December 2019, the COVID-19 pandemic started to spread from Hubei province in China. Currently there are many affected countries worldwide, including Saudi Arabia. This study aimed to assess the use of social media as a source for COVID-19 awareness in Saudi Arabia. An online survey was conducted between 9 and 13 May 2020 and a total of 3,204 subjects participated in the survey. We used snowball sampling techniques through an online structured questionnaire. The data were cleaned, coded and analysed using the Statistical Package for the Social Sciences SPSS version 25.0. A chi-square test was used to find the associations between variables. Of all participants, 75.4% had a high level of awareness of the COVID-19 pandemic. Saudi participants above 18 years old and medical practitioners showed a high level of awareness. All participants from all regions of Saudi Arabia showed a high level of awareness except for those from the northern region. The most common source of information was the official government social media, and 44.1% reported the use of Twitter. Our findings show that social media have a positive impact on the circulation of information about the COVID-19 pandemic in Saudi Arabia.
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December 2020

Clinicopathologic Features and the Association with Short-Term Outcome of Primary Membranous Nephropathy in Children: A Single-Center Study from Pakistan.

Saudi J Kidney Dis Transpl 2020 Sep-Oct;31(5):1078-1084

Department of Pediatric Nephrology, Sindh Institute of Urology and Transplantation, Karachi, Pakistan.

Membranous nephropathy (MN) is an uncommon cause of steroid-resistant nephrotic syndrome in children. Our study aimed to determine the clinicopathologic features of primary MN in children and their association with short-term outcome. This observational study was conducted from January 2009 to June 2017 at the Pediatric Nephrology Department. A total of 50 children were diagnosed with primary MN. Their clinical, laboratory, and histopathological findings on renal biopsy were recorded. The minimum follow-up was for six months. Clinicopathologic features were correlated with the outcome at the last follow-up. Data analysis was done using IBM SPSS Statistics for Windows software version 20.0. The mean age at onset was 10.92 ± 3.08 years (range: 4-17 years). The male-to-female ratio was 3:1. The serum albumin of ≤2.5 g/dL was seen in 40 patients (80%), hypertension was present in 38 (76%), and heavy proteinuria was seen in 32 children (70%). The mean estimated glomerular filtration rate (eGFR) at presentation was 178.71 ± 0.78 mL/min/1.73 m. At the initial visit, nine children (18.4%) were in chronic kidney disease stage 2 and one (2%) in stage 4. Phospholipase A receptor antibody was present in five (15%) of 32 children tested. At the last follow-up (28 interquartile range: 25.5 months), 11 children (26%) were in complete remission and 25 (66%) had achieved partial remission. The mean eGFR had reduced to 145.84 ± 78.05 mL/min/1.73 m. Patients with normal initial eGFR were more likely to go into remission (P = 0.001). The short-term outcome of childhood primary MN is relatively good in our setup. A multicenter collaborative study is required to determine prognostic factors and to standardize treatment in this uncommon nephropathy.
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http://dx.doi.org/10.4103/1319-2442.301174DOI Listing
November 2020

Impact of One-Year Serum Creatinine on Long-term Renal Graft Survival in a Living-Related Renal Transplant Program.

Saudi J Kidney Dis Transpl 2020 Sep-Oct;31(5):998-1005

Department of Urology, Sindh Institute of Urology and Transplantation, Karachi, Pakistan.

This study was carried out to determine the impact of one-year posttransplant serum creatinine (SCr) levels on the long-term outcomes of living-related donor kidney transplants. A retrospective cohort study included 773 adult living-related renal transplant recipients from 2010 to 2012, with a minimum follow-up period of five years. Demographics and posttransplantation follow-up data including immunosuppression regimens, rejection episodes, and survival rates were evaluated. Patients were divided into four cohorts (G1, G2, G3, and G4 based on SCr at the end of the 1 year: G1, SCr <88.4 μ mol/L; G2, 88.5≤ SCr ≤ 132.6 μmol/L; G3, 132.7≤ SCr ≤176.8 mol/L; and G4, SCr ≥176.9 μ mol/L). Comparisons between the groups used the Chi-square test for qualitative parameters and analysis of variance for continuous variables. Five-year graft survival for G1 was 98% as compared to 76% in G4 (P <0.001). Recipients of G4 encountered more acute rejection episodes in 21% of the cases as compared to 7.3% in G1 (P = 0.001). Donors were older in G4 (42.07 ± 10.4 years) as compared to G1 (30.1 ± 8.5 years) (P = 0.001). A third of the donors in G1 were HLA identical as compared to 7% in G4. Prediction of long-term graft survival is possible by the SCr level at one year post transplant. This can be of great importance, especially to identify those patients who require close monitoring in follow-up. Donor age, HLA, and acute rejection impact SCr at one year and hence graft outcome.
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http://dx.doi.org/10.4103/1319-2442.301204DOI Listing
November 2020

COVID-19 and Biomedical Publishing: Challenges and Prospects.

Authors:
Muhammed Mubarak

J Coll Physicians Surg Pak 2020 10;30(10):92-93

Department of Histopathology, Sindh Institute of Urology and Transplantation (SIUT), Karachi, Pakistan.

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http://dx.doi.org/10.29271/jcpsp.2020.supp2.92DOI Listing
October 2020

Immunomodulatory Effects of Diterpenes and Their Derivatives Through NLRP3 Inflammasome Pathway: A Review.

Front Immunol 2020 25;11:572136. Epub 2020 Sep 25.

Zabol Medicinal Plants Research Center, Zabol University of Medical Sciences, Zabol, Iran.

Nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing protein (NLRP) inflammasomes are involved in the molecular pathogenesis of many diseases and disorders. Among NLRPs, the NLRP3 (in humans encoded by the gene) is expressed predominantly in macrophages as a component of the inflammasome and is associated with many diseases, including gout, type 2 diabetes, multiple sclerosis, atherosclerosis, and neurological diseases and disorders. Diterpenes containing repeated isoprenoid units in their structure are a member of some essential oils that possess diverse biological activities and are becoming a landmark in the field of drug discovery and development. This review sketches a current scenario of diterpenes or their derivatives acting through NLRPs, especially NLRP3-associated pathways with anti-inflammatory effects. For this, a literature survey on the subject has been undertaken using a number of known databases with specific keywords. Findings from the aforementioned databases suggest that diterpenes and their derivatives can exert anti-inflammatory effects NLRPs-related pathways. Andrographolide, triptolide, kaurenoic acid, carnosic acid, oridonin, teuvincenone F, and some derivatives of tanshinone IIA and phorbol have been found to act through NLRP3 inflammasome pathways. In conclusion, diterpenes and their derivatives could be one of the promising compounds for the treatment of NLRP3-mediated inflammatory diseases and disorders.
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http://dx.doi.org/10.3389/fimmu.2020.572136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7546345PMC
September 2020

Ethnomedicinal documentation and anti-inflammatory effects of n-butanol extract and of four compounds isolated from the stems of Pituranthos scoparius: An in vitro and in vivo investigation.

J Ethnopharmacol 2021 Mar 20;267:113488. Epub 2020 Oct 20.

Department of Chemistry, The University of Jordan, Amman, 11942, Jordan; Department of Chemistry, Indiana University, Bloomington, IN, 47405, United States. Electronic address:

Ethnopharmacological Relevance: Pituranthos scoparius is a medicinal plant belonging to the Apiaceae family. It thrives in North Africa, and is widely distributed in the high plateau of most parts of the Sahara in Algeria. This plant is widely used in the Algerian traditional medicine to treat numerous infectious diseases, dermatoses, nervous breakdowns, digestive disorders, and calm abdominal pain.

Aim Of The Study: The aim of the present work was to examine the ethnomedicinal uses of Pituranthos scoparius in Setif region, Algeria, isolate and identify the chemical constituents of the n-butanol stem extract of P. scoparius (BEPS), and to determine the toxicity and anti-inflammatory effects of these compounds in addition to the extract.

Materials And Methods: The anti-inflammatory effects of BEPS and the four compounds isolated from the extract were evaluated using the in vitro protein denaturation assay, whereas the topical anti-inflammatory activity was assessed using the croton oil-induced ear edema in mice. Toxicity was determined based on assessment of in vitro cytotoxicity using hemolytic activity against human red blood cells (RBCs).

Results: Four compounds, identified as the rare isorhamnetin-3-O-β-apiofuranosyl (1 → 2)-β glucopyranoside (2), in addition to three known compounds, namely isorhamnetin-3-O-β-glucoside (1), D-mannitol (3), and isorhamnetin-3-O-β-glucopyranosyl-(1 → 6)-β-glucopyranoside (4) were isolated from BEPS. These compounds were characterized by means of NMR and high-resolution mass spectral (HRMS) data. These four compounds were isolated for the first time from this traditional Algerian medicinal plant. Screening of the extract indicated the presence of alkaloids, polyphenols, flavonoids, free quinones, coumarins and tannins. Topical anti-inflammatory effect showed that the four isolated compounds, as well as BEPS, exhibit a significant (p < 0.05) dose-dependent (0.5 and 1 mg/ear) anti-inflammatory effect. At a dose of 1 mg/ear, compounds 1, 2, and 4, exhibited remarkable anti-inflammatory effect with a percentage inhibition of 85.50 ± 2.78, 79.78 ± 4.68, and 75.78 ± 2.98%, respectively. Results from in vitro cytotoxicity showed that the % lysis of the extract, along with isolated compounds was found to be virtually nontoxic.

Conclusions: These results suggest that BEPS and isolated compounds are safe, nontoxic, and exert remarkable anti-inflammatory effects, and can be new sources of natural anti-inflammatory agents.
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http://dx.doi.org/10.1016/j.jep.2020.113488DOI Listing
March 2021

High-grade vesicoureteral reflux in infants: Our experience with endoscopic subureteric injections.

Urologia 2020 Oct 16:391560320966187. Epub 2020 Oct 16.

Department Surgery, Salmaniya Medical Complex, Manama, Kingdom of Bahrain.

Background: Vesicoureteral reflux (VUR) is the most common urological anomaly in pediatric patients. Management options for VUR vary from continuous antibiotic prophylaxis (CAP) to surgery via either endoscopic subureteric injection of a bulking agent or open anti-reflux surgery. In this study, we assess the efficacy of subureteric injections of Dextranomer/Hyaluronic acid Copolymer (Deflux) in managing primary VUR in infant patients with high-grade VUR.

Methods: From 2010 to 2015, children less than 1-year-old with primary high-grade VUR were observed prospectively following the administration of endoscopic subureteric injections of Dextranomer/Hyaluronic Acid Copolymer (Deflux). The diagnosis of VUR was based on MCUG, and all patients underwent a holistic clinical, laboratory, and radiological assessment before and after the intervention. Complete success was defined as the resolution of VUR on follow up 1 year post-operatively.

Results: A total of 30 infants (50 renal units) with high-grade VUR (grades IV and V) were included in the study. The mean age at surgery was 6.3 ± 2.5 months. Most of the patients presented with a urinary tract infection (90%). Complete symptomatic relief was achieved in 27 patients (90%) at the first post-operative follow-up. Forty-four renal units received one injection, while six required a second injection as they did not meet our treatment success criteria. No patients required a third injection or referral for open surgery.

Conclusion: Endoscopic injection of Dextranomer/Hyaluronic acid Copolymer (Deflux) at the vesicoureteral junction is an effective minimally invasive intervention to treat high grades VUR (IV-V) infants.
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http://dx.doi.org/10.1177/0391560320966187DOI Listing
October 2020

How Does Replacement of the Axial Histidine Ligand in Cytochrome Peroxidase by N-Methyl Histidine Affect Its Properties and Functions? A Computational Study.

Int J Mol Sci 2020 Sep 27;21(19). Epub 2020 Sep 27.

Manchester Institute of Biotechnology, The University of Manchester, 131 Princess Street, Manchester M1 7DN, UK.

Heme peroxidases have important functions in nature related to the detoxification of HO. They generally undergo a catalytic cycle where, in the first stage, the iron(III)-heme-HO complex is converted into an iron(IV)-oxo-heme cation radical species called Compound I. Cytochrome peroxidase Compound I has a unique electronic configuration among heme enzymes where a metal-based biradical is coupled to a protein radical on a nearby Trp residue. Recent work using the engineered N-methyl histidine-ligated cytochrome peroxidase highlighted changes in spectroscopic and catalytic properties upon axial ligand substitution. To understand the axial ligand effect on structure and reactivity of peroxidases and their axially N-methyl histidine engineered forms, we did a computational study. We created active site cluster models of various sizes as mimics of horseradish peroxidase and cytochrome peroxidase Compound I. Subsequently, we performed density functional theory studies on the structure and reactivity of these complexes with a model substrate (styrene). Thus, the work shows that the N-methyl histidine group has little effect on the electronic configuration and structure of Compound I and little changes in bond lengths and the same orbital occupation is obtained. However, the N-methyl histidine modification impacts electron transfer processes due to a change in the reduction potential and thereby influences reactivity patterns for oxygen atom transfer. As such, the substitution of the axial histidine by N-methyl histidine in peroxidases slows down oxygen atom transfer to substrates and makes Compound I a weaker oxidant. These studies are in line with experimental work on N-methyl histidine-ligated cytochrome peroxidases and highlight how the hydrogen bonding network in the second coordination sphere has a major impact on the function and properties of the enzyme.
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http://dx.doi.org/10.3390/ijms21197133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7583937PMC
September 2020

Curcumin and its Multi-target Function Against Pain and Inflammation: An Update of Pre-clinical Data

Curr Drug Targets 2020 09 25. Epub 2020 Sep 25.

Department of Chemistry, The University of Jordan, Amman 11942, Jordan.

Pain is an unpleasant sensation that have complex and various causative etiology. Modern drug discovery fo-cuses on identifying potential molecules that target multiple pathways with safer profile compared to those with a single target. Current treatment of pain and inflammation with the available therapeutics has a number of major side effects. Pain is one of the major clinical problems that needs functional therapeutics which act on multiple targets and with low toxici-ty. Curcumin, a naturally occurring polyphenolic compound from Curcuma longa, has been used for years in Ayurvedic, Chinese, and in many other systems of traditional medicine. Pre-clinical data published thus far, demonstrated that curcu-min possesses multi-target biological functions, suggesting its potential use to cure different diseases. However, there is no or little systematic review on its potential use in pain and inflammation with underlying mechanisms for such activi-ties. Accordingly, the aim of the current review was to update the pre-clinical data of curcumin and its multiple targeting pathways for analgesic and anti-inflammatory action, and to further propose a molecular mechanism. Literature study was conducted using different known databases including Pubmed, Sci-finder, Google scholar, and Science Direct. Available pre-clinical data suggest the ameliorating effect of curcumin in pain and inflammation is rendered through the modulation of a of pain pathways including inhibition of a number of pro-inflammatory mediators, inhibition of oxidative stress and Cox-2, down-regulation of Ca2+/calmodulin-depend protein kinase II (CaMKIIα) and calcium channels like transient re-ceptor potential (TRP), modulation of metabotropic glutamate receptor-2 (mGlu2), modulation of monoamine system, in-hibition of JAK2/STAT3 signaling pathway, remodeling of extracellular matrix proteins, inhibition of apoptosis, inhibi-tion of JNK/MAPK and ERK/CREB signaling pathway, and activation of opioid system. Taken all together, it is evident that curcumin is one of the promising safe natural polyphenolic molecules that target multiple molecular pathways in pain, and can be beneficial in the treatment and management of pain and inflammation.
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http://dx.doi.org/10.2174/1389450121666200925150022DOI Listing
September 2020

Recent Advances in the Synthesis and Biological Activity of 8-Hydroxyquinolines.

Molecules 2020 Sep 21;25(18). Epub 2020 Sep 21.

Department of Chemistry, School of Science, The University of Jordan, Amman 11942, Jordan.

Compounds containing the 8-hydroxyquinoline (8-HQ) nucleus exhibit a wide range of biological activities, including antimicrobial, anticancer, and antifungal effects. The chemistry and biology of this group have attracted the attention of chemists, medicinal chemists, and professionals in health sciences. A number of prescribed drugs incorporate this group, and numerous 8-HQ- based molecules can be used to develop potent lead compounds with good efficacy and low toxicity. This review focusses on the recent advances in the synthesis of 8-HQ derivatives with different pharmacological properties, including anticancer, antiviral, and antibacterial activities. For this purpose, recent relevant references were searched in different known databases and search engines, such as MEDLINE (PubMed), Google Scholar, Science Direct, Scopus, Cochrane, Scientific Information Database (SID), SciFinder, and Institute for Scientific Information (ISI) Web of Knowledge. This review article provides a literature overview of the various synthetic strategies and biological activities of 8-HQ derivatives and covers the recent related literature. Taken together, compounds containing the 8-HQ moiety have huge therapeutic value and can act as potential building blocks for various pharmacologically active scaffolds. In addition, several described compounds in this review could act leads for the development of drugs against numerous diseases including cancer.
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http://dx.doi.org/10.3390/molecules25184321DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7571046PMC
September 2020

Piperine: A review of its biological effects.

Phytother Res 2021 Feb 14;35(2):680-700. Epub 2020 Sep 14.

Department of Chemistry, The University of Jordan, Amman, Jordan.

Medicinal plants have been used for years as a source of food, spices, and, in traditional medicine, as a remedy to numerous diseases. Piper nigrum, belonging to the family Piperaceae is one of the most widely used spices all over the world. It has a distinct sharp flavor attributed to the presence of the phytochemical, piperine. Apart from its use as a spice, P. nigrum is frequently used for medicinal, preservation, and perfumery purposes. Black pepper contains 2-7.4% of piperine, varying in content is associated with the pepper plant. Piperine displays numerous pharmacological effects such as antiproliferative, antitumor, antiangiogenesis, antioxidant, antidiabetic, anti-obesity, cardioprotective, antimicrobial, antiaging, and immunomodulatory effects in various in vitro and in vivo experimental trials. Furthermore, piperine has also been documented for its hepatoprotective, anti-allergic, anti-inflammatory, and neuroprotective properties. This review highlights and discusses the medicinal and health-promoting effects of piperine, along with possible mechanisms of its action in health promotion and disease prevention. In addition, the present review summarizes the recent literature related to piperine as a therapeutic agent against several diseases.
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http://dx.doi.org/10.1002/ptr.6855DOI Listing
February 2021

Anti-inflammatory and In Silico Docking Studies of Heterophragma adenophyllum Seem Stem Constituents.

Inflammation 2021 Feb 8;44(1):297-306. Epub 2020 Sep 8.

Laboratory of Biological Control and Antimicrobial Resistance, Orel State University named after I.S. Turgenev, Orel City, 302026, Russia.

Heterophragma adenophyllum is a traditional medicinal plant that has been used as anti-inflammatory and to relief muscular tension. In the current research, four isolated constitutes namely lapacho (1), peshawaraquinone (2), indanone derivatives (3), α-lapachone (4) of H. adenophyllum were tested for anti-inflammatory effect using the carrageenan- and histamine-induced paw edema paradigm. The tested compounds (1-4) were evaluated for anti-inflammatory effect during the early and late phase of edema induction. In the early phase, all tested compounds (0.5 2.5 mg/kg each i.p.) demonstrated less than 50% effect, while in the later phase, compounds (2 and 3) demonstrated 85.66 and 89.87% attenuation. In addition, compounds (1-4) were subjected to histamine-induced inflammation, where compounds 2 and 3 exhibited excellent effects 86.87 and 89.98%, respectively at 5 mg/kg after the 2nd hour of administration, whereas compounds 1 and 4 did not exhibit any significant effect as compared with the negative control. Molecular docking results revealed a very high potency of compound based on the protein-ligand interaction (PLI) profile, which was further evaluated through a molecular dynamic simulation study. Therefore, the anti-inflammatory effect of H. adenophyllum attributed to the presence of these bioactive compounds (1-4) strongly supports the traditional uses of H. adenophyllum for treatment of inflammation. However, compounds 2 and 3 which exerted anti-inflammatory effect must be subjected for further mechanistic studies.
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http://dx.doi.org/10.1007/s10753-020-01333-7DOI Listing
February 2021

Citrinin against breast cancer: A cytogenotoxicological study.

Phytother Res 2021 Jan 31;35(1):504-516. Epub 2020 Aug 31.

Northeast Biotechnology Network (RENORBIO), Postgraduate Program in Biotechnology, Federal University of Piauí - UFPI, Teresina, Piauí, Brazil.

Breast cancer is one of the most lethal types of cancer and a leading cause of mortality among Women worldwide. Citrinin (CIT), a polyketide extracted from the fungus Penicillium citrinum, exhibits a wide range of biological activities such as antibacterial, antifungal, and cytotoxic effects. The aim of the current study was to evaluate the antitumoral effects of CIT against 7,12-dimethylbenzanthracene (DMBA)-induced mammary carcinoma in Swiss mice For this, CIT, DMBA and the standard cyclophosphamide (CPA) induced behavioral changes in experimental animals, and these changes were screened by using the rota rod and open field tests. Additionally, hematological, biochemical, immuno-histochemical, and histopathological analyses were carried out. Results suggest that CIT did not alter behavioral, hematological, and biochemical parameters in mice. DMBA induced invasive mammary carcinoma and showed genotoxic effects in the breasts, bone marrow, lymphocytes, and hepatic cells. It also caused mutagenic effects in the formation of micronuclei, bridges, shoots, and binucleate cells in bone marrow and liver. CIT and CPA genotoxic effects were observed after 3 weeks of therapy, where CIT exhibited a repair capacity and induced significant apoptotic damage in mouse lymphocytes. In conclusion, CIT showed antitumoral effects in Swiss mice, possibly through induction of apoptosis.
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http://dx.doi.org/10.1002/ptr.6830DOI Listing
January 2021

Catalytic Mechanism of Aromatic Nitration by Cytochrome P450 TxtE: Involvement of a Ferric-Peroxynitrite Intermediate.

J Am Chem Soc 2020 09 2;142(37):15764-15779. Epub 2020 Sep 2.

The Manchester Institute of Biotechnology, The University of Manchester, 131 Princess Street, Manchester M1 7DN, United Kingdom.

The cytochromes P450 are heme-dependent enzymes that catalyze many vital reaction processes in the human body related to biodegradation and biosynthesis. They typically act as mono-oxygenases; however, the recently discovered P450 subfamily TxtE utilizes O and NO to nitrate aromatic substrates such as L-tryptophan. A direct and selective aromatic nitration reaction may be useful in biotechnology for the synthesis of drugs or small molecules. Details of the catalytic mechanism are unknown, and it has been suggested that the reaction should proceed through either an iron(III)-superoxo or an iron(II)-nitrosyl intermediate. To resolve this controversy, we used stopped-flow kinetics to provide evidence for a catalytic cycle where dioxygen binds prior to NO to generate an active iron(III)-peroxynitrite species that is able to nitrate l-Trp efficiently. We show that the rate of binding of O is faster than that of NO and also leads to l-Trp nitration, while little evidence of product formation is observed from the iron(II)-nitrosyl complex. To support the experimental studies, we performed density functional theory studies on large active site cluster models. The studies suggest a mechanism involving an iron(III)-peroxynitrite that splits homolytically to form an iron(IV)-oxo heme (Compound II) and a free NO radical via a small free energy of activation. The latter activates the substrate on the aromatic ring, while compound II picks up the -hydrogen to form the product. The calculations give small reaction barriers for most steps in the catalytic cycle and, therefore, predict fast product formation from the iron(III)-peroxynitrite complex. These findings provide the first detailed insight into the mechanism of nitration by a member of the TxtE subfamily and highlight how the enzyme facilitates this novel reaction chemistry.
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http://dx.doi.org/10.1021/jacs.0c05070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7586343PMC
September 2020

Anti-Inflammatory, Antinociceptive, and Antioxidant Properties of Anacardic Acid in Experimental Models.

ACS Omega 2020 Aug 29;5(31):19506-19515. Epub 2020 Jul 29.

RENORBIO - Post-Graduation Program in Biotechnology, Federal University of Piauí, Teresina 64049-550, Piauí, Brazil.

Anacardic acid (AA), a compound extracted from cashew nut liquid, exhibits numerous pharmacological activities. The aim of the current investigation was to assess the anti-inflammatory, antinociceptive, and antioxidant activities of AA in mouse models. For this, Swiss albino mice were pretreated with AA (10, 25, 50 mg/kg, intraperitoneally, ip) 30 min prior to the administration of carrageenan, as well as 25 mg/kg of prostaglandin E2, dextran, histamine, and compound 48/80. The antinociceptive activity was evaluated by formalin, abdominal, and hot plate tests, using antagonist of opioid receptors (naloxene, 3 mg/kg, ip) to identify antinociceptive mechanisms. Results from this study revealed that AA at 25 mg/kg inhibits carrageenan-induced edema. In addition, AA at 25 mg/kg reduced edema and leukocyte and neutrophilic migration to the intraperitoneal cavity, diminished myeloperoxidase activity and malondialdehyde concentration, and increased the levels of reduced glutathione. In nociceptive tests, it also decreased licking, abdominal writhing, and latency to thermal stimulation, possibly via interaction with opioid receptors. Taken together, these results indicate that AA exhibits anti-inflammatory and antinociceptive actions and also reduces oxidative stress in acute experimental models, suggesting AA as a promising compound in the pharmaceutical arena.
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http://dx.doi.org/10.1021/acsomega.0c01775DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7424580PMC
August 2020

Biogenically Synthesized Polysaccharides-Capped Silver Nanoparticles: Immunomodulatory and Antibacterial Potentialities Against Resistant .

Front Bioeng Biotechnol 2020 21;8:643. Epub 2020 Jul 21.

Department of Chemistry, The University of Jordan, Amman, Jordan.

Bacterial infections are the key cause of death in patients suffering from burns and diabetic wounds while the use of traditional antibiotics has been growing steadily. Thus, in the present study, we are trying to introduce a paradigm shift strategy to improve chronic wound healing of bacterial infection. To that end, we have biologically synthesized silver nanoparticles (AgNPs) using polysaccharides, and evaluated their antibacterial efficacy with their safety pattern. Scanning electron micrographs showed spherical AgNPs coated with algal polysaccharides with an approximate size of 9.7 nm. Treatment of with the AgNPs (0.5-1 μg/mL) resulted in a significant disruption in outer membrane, reduction in biofilm formation, and a significant decrease of production of alginate and pyocyanin along with a concentration-dependent reduction in β-lactamase activity. In addition, at the level, AgNPs displayed substantial activity to control infections in rat skin wounds with significant reduction in in COX-2 enzyme in both rat skin homogenate and serum samples. Furthermore, AgNPs facilitated wound curative in the infected model by reducing the hemorrhagic areas number and the infiltrated inflammatory cells. Taken all together, these biogenic nanoparticles showed unique properties in controlling bacterial wound infections and improving the healing process of damaged tissues via its direct and indirect effects.
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http://dx.doi.org/10.3389/fbioe.2020.00643DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7391905PMC
July 2020

Antioxidant and Antidiabetic Potentials of L. Alston.

Evid Based Complement Alternat Med 2020 28;2020:9529042. Epub 2020 Jul 28.

Herbal Technology Section (HTS), Modern Research & Development Complex (MRDC), Industrial Technology Institute (ITI), 503A Halbarawa Gardens, Malabe, Sri Lanka.

L. Alston (Family: Myrtaceae, Sinhala: Heendan) is a red-listed plant that has been used in traditional medicine in Sri Lanka for the treatment of diabetes, but it is yet to be exploited for its potential uses as a functional food or a source of supplements. The present study focused on the evaluation of antidiabetic property of fruits and leaves assessing antioxidant, antiglycation, and antiamylase activities and functional mineral element composition. The crude extracts (CR) of leaves and fruits were fractionated into hexane (Hex) ethyl acetate (EA) and aqueous (AQ) and evaluated for bioactivities along with the crude extracts. The isolated fraction (C) of Hex fraction of fruit showed significantly high ( < 0.05) antiamylase activity with IC value 2.27 ± 1.81 g/mL where the Hex fraction of fruits exhibited the IC value as 47.20 ± 0.3 g/mL which was higher than acarbose (IC: 87.96 ± 1.43 g/mL). The EA fraction of leaves showed highest values for DPPH radical scavenging activity, ferric reducing antioxidant power, and oxygen radical absorbance capacity. Significantly high ( < 0.05) ABTS radical scavenging activity and iron chelating activity were observed in Hex fraction of fruit. The composition of volatiles in leaf oil was studied with GC-MS, and 58 compounds were identified. Inductively coupled plasma-mass spectrometry data revealed the presence of biologically significant trace elements such as Fe, Zn, Mg, Cu, Se, and Sr in leaves and fruits. It is concluded that the Hex fraction of fruits will be a good source for the formulation of supplements for diabetic management with further evaluation of potency and efficacy.
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http://dx.doi.org/10.1155/2020/9529042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7407018PMC
July 2020

Factors influencing vaccination coverage among children age 12-23 months in Afghanistan: Analysis of the 2015 Demographic and Health Survey.

PLoS One 2020 7;15(8):e0236955. Epub 2020 Aug 7.

Department of Microbiology, Kabul University of Medical Sciences, Kabul, Afghanistan.

Background: Childhood vaccination plays a key role in reducing morbidity and mortality from vaccine-preventable diseases. Numerous studies have assessed the influence of demographic and socioeconomic factors on child immunization around the world. There are few such studies in Afghanistan, however. Therefore, this study aimed to identify factors influencing vaccination status among children age 12-23 months in Afghanistan.

Materials And Methods: Nationally representative data from the 2015 Afghanistan Demographic and Health Survey were used for this study. A sample of 5,708 children age 12-23 months with a vaccine card and immunization history was analyzed. Multinomial logistic regression was used to identify significant relationships between cofactors and vaccination status.

Results: In the study, 51% the subjects were boys, 48% were born at home, and 76% were residents of rural areas. Background characteristics positively associated with vaccination status included delivery in a health facility (RRR = 2.5, 95% CI = 1.9-3.3), maternal age of 30-39 years (RRR = 2.2, 95% CI = 1.2-4.1), attending at least four visits for antenatal care (RRR = 2.7, 95% CI = 1.7-4.5), health facility visit in the past 12 months (RRR = 1.9, 95% CI = 1.4-2.5), paternal professional occupation (RRR = 4.9, 95% CI = 2.0-12.3), family with richer wealth index (RRR = 2.4, 95% CI = 1.4-4.1), and living in the northeast region (RRR = 2.2, 95% CI = 1.2-3.9)were positively associated with vaccination status. Living in the southern region (RRR = 0.3, 95% CI = 0.2-0.5) was negatively associated with vaccination status.

Conclusion: This study identified maternal age, ANC visits, place of delivery, health facility visits in past 12 months, paternal occupation, wealth quintile, and geographic region as the factors influencing child's vaccination status in Afghanistan.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0236955PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7413477PMC
October 2020