Publications by authors named "Ajmal Khan"

262 Publications

Green synthesis and biomedicinal applications of silver and gold nanoparticles functionalized with methanolic extract of .

Artif Cells Nanomed Biotechnol 2021 Dec;49(1):194-203

Natural and Medical Sciences Research Center, University of Nizwa, Nizwa, Sultanate of Oman.

This study deals with facile and rapid synthesis of silver nanoparticles (AgNPs) and Gold nanoparticles (AuNPs) using leaves extracts (MLE). The synthesized AgNPs and AuNPs were characterized by UV-visible spectroscopy (UV-Vis), Fourier transformed infra-red spectroscopy (FT-IR), atomic force microscopy (AFM) and transmission electron microscopy (TEM) techniques. The phytochemical analysis showed the presence of bioactive secondary metabolites, which are involved in the synthesis of nanoparticles (NPs). The surface plasmon resonance (SPR) observed at 435 and 550 nm, confirmed the green synthesis of AgNPs and AuNPs, respectively. The TEM images showed poly dispersed and round oval shapes of Ag and Au NPs with an average particles size of 10.23 ± 2 nm and 13.45 ± 2 nm, respectively. TEM results are in close agreements with that of AFM analysis. The FT-IR spectroscopy revealed the presence of OH, -NH and C = O groups, which involved in the synthesis of NPs. The MLE and their AgNPs and AuNP exhibited good antibacterial and anti-oxidant activities. Moreover, MLE and NPs also showed analgesic activities in mice, and excellent sedative properties in open field test paradigm.
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http://dx.doi.org/10.1080/21691401.2021.1890099DOI Listing
December 2021

Therapeutic potential of N-substituted thiosemicarbazones as new urease inhibitors: Biochemical and in silico approach.

Bioorg Chem 2021 Feb 2;109:104691. Epub 2021 Feb 2.

Institute of Chemical Sciences, Bahauddin Zakariya University, Multan 60800, Pakistan. Electronic address:

Urease enzyme plays a key role in pathogenesis of gastritis and peptic ulcers. Its inhibition averts our bodies from many disorders including formation of urinary calculi. In agriculture, the high urease content causes severe environmental and hence economic problems. Due to deficiency of effective and safer drugs to tackle the aforementioned disorders, the quest for new scaffolds becomes mandatory in the field of medicinal chemistry. In this regard, we herein report a new series of N-substituted thiosemicarbazones 3a-v as potential candidates for urease inhibition. These new N-substituted thiosemicarbazones 3a-v of distant chemical scaffolds were characterized by advanced spectroscopic techniques, such as FTIR, HNMR, CNMR, ESI-MS and in the case of compound 3g by single crystal X-ray analysis. The compounds were evaluated for their urease inhibitory potential. All newly synthesized compounds showed significant urease inhibitions with IC values in range of 2.7 ± 0.320-109.2 ± 3.217 μM. Molecular docking studies were used for interactions pattern and structure-activity relationship for all compounds, which demonstrated excellent binding interactions with the active site residues, such as hydrogen bonding, π-π interactions, π-H and nickel atom coordination.
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http://dx.doi.org/10.1016/j.bioorg.2021.104691DOI Listing
February 2021

Green synthesis, in vivo and in vitro pharmacological studies of Tamarindus indica based gold nanoparticles.

Bioprocess Biosyst Eng 2021 Feb 13. Epub 2021 Feb 13.

Department of Crop Science, College of Sanghuh Life Science, Konkuk University, Seoul, 05029, Republic of Korea.

The current investigation aims to synthesize gold nanoparticles (AuNPs) from aqueous extract of Tamarindus indica and to evaluate the in vitro anti-bacterial and in vivo sedative and anelgescic activities of crude extract as well as synthesized AuNPs. Several methods have been reported to synthesize AuNPs; however, most of them were not ecofriendly. In the present study, the green synthesis of AuNPs has been carried out. Using the green synthesis method, AuNPs of T. indica were synthesized at room temperature (25 °C) by mixing 5 mL of HAuCl (1 mM) with 1 mL of T. indica seed extract solution. This extract solution was prepared by taking 5 gm dry seeds in 100 mL of double deionized water with continuous stirring for up to 24 h at 80 °C. The stability of AuNPs was confirmed with the help of relevant experimental techniques including ultraviolet-visible (UV/Vis) showing maximum absorbance at 535-540 nm, Fourier transform infrared showing a broad signal at 3464 cm which can be attributed to either amide or hydroxyl functionalities and atomic force microscopy analysis showed that the biomaterial surrounding AuNPs was agglomerated which proves the formation of discrete nanostructutres. These AuNPs have been evaluated for their antibacterial potential. The results revealed good antibacterial activity of the samples against. Klebsiella pneumonia, Bacillus subtilis and Staphylococcus epidermidis with 10-12 mm zone of inhibition range. The AuNPs were also found stable at high temperature, over a range of pH and in 1 mM salt solution. Moreover, the crude extract and respective AuNPs also exhibited interesting sedative and analgesic activities. Hence, we focused on phytochemicals-mediated synthesis of AuNPs considered as greatest attention in the treatment of anti-bacterial, analgesic, and sedative.
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http://dx.doi.org/10.1007/s00449-020-02500-8DOI Listing
February 2021

Assessment of DNA damage induced by endosulfan in grass carp (Ctenopharyngodon idella Valenciennes, 1844).

Environ Sci Pollut Res Int 2021 Feb 6. Epub 2021 Feb 6.

Department of Zoology, University of Peshawar, Peshawar, Khyber Pakhtunkhwa, Pakistan.

Endosulfan is an organochlorine pesticide, which is commonly used throughout the world. It accumulates in the environment and may cause significant damage to the ecosystems, particularly to the aquatic environments. The present study was conducted to evaluate the genotoxic effect of endosulfan on the grass carp (Ctenopharyngodon idella) blood. The fish were exposed to three different concentrations, 0.75 ppb/day, 1.0 ppb/day, and 1.5ppb/day of endosulfan for 7, 14, 21, and 28 days. The study was a randomized control trial and the control group was not exposed to endosulfan. The results showed that after 7 days, the level of DNA damage in all the concentrations was significant (P < 0.05), while after 14, 21, and 28 days' trials, highly significant (P < 0.000) level of DNA damage was observed. Hence, time- and dose-dependent DNA damage was observed in fish DNA by comet assay. It is concluded from our results that with the increase in endosulfan concentration and exposure duration, the level of DNA damage also increased. As the current study showed the severe genotoxic effect of endosulfan in Ctenopharyngodon idella, therefore, the imprudent and indiscriminate use of endosulfan should be controlled and monitored by the concerned government authorities.
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http://dx.doi.org/10.1007/s11356-021-12727-xDOI Listing
February 2021

Attenuation of nociceptive and paclitaxel-induced neuropathic pain by targeting inflammatory, CGRP and substance P signaling using 3-Hydroxyflavone.

Neurochem Int 2021 Mar 5;144:104981. Epub 2021 Feb 5.

Natural and Medical Sciences Research Center, University of Nizwa, Birkat-ul-Mouz 616, Nizwa, Oman. Electronic address:

Paclitaxel is an anti-microtubule agent, most widely used chemotherapeutic agent for the treatment of malignant solid tumors. However, it is associated with some severe side effects including painful neurotoxicity with reporting of neuropathic pain and sensory abnormalities by patients during and after paclitaxel therapy. Peripheral neuropathy was induced by the administration of paclitaxel (4 mg/kg on days 1, 3, 5, and 7). In this study, the anti-nociceptive and anti-inflammatory propensity of 3-Hydroxyflavone (3HF) in mice and the preventive effect of 3HF against paclitaxel-induced peripheral neuropathy in Sprague Dawley (SD) rats were investigated. Moreover, tactile and cold allodynia, thermal and tail immersion hyperalgesia, and effects on motor-coordination were also evaluated. Furthermore, the expression of proinflammatory cytokines i.e. Calcitonin gene-related peptide (CGRP), and Substance P from the spinal cord was examined through RT-PCR. Additionally, a computational structural biology approach was applied to search the potential therapeutic targets and to predict the binding mechanism of 3HF. Treatment of 3HF alleviated the nociceptive pain, paw edema, development of tactile and cold allodynia, and hyperalgesia. Similarly, treatment with 3HF suppressed the paclitaxel-induced increase in mRNA expression of several inflammatory cytokines including tumor necrosis factor -α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6), CGRP, and Substance P. However, the daily treatment of 3HF did not affect the motor behaviors of rats. The inhibitory mechanism of 3HF in neuropathic pain is predicted with extensive computational bioinformatics approach which indicates that the 3HF effectively interacts with the binding domains of Nuclear factor-kappa B (NF-κB), CGRP receptor and the receptor of Substance P to exert its inhibitory activities. However, the computationally predicted binding affinities revealed that the potential of binding of the compound with Substance P receptor (Neurokinin 1 receptor) is higher than the other receptors; there NK1R could be the most possible binding target of 3HF. These findings indicate that 3HF has anti-nociceptive, anti-inflammatory, and anti-neuropathic pain effects against paclitaxel-induced neuropathic pain.
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http://dx.doi.org/10.1016/j.neuint.2021.104981DOI Listing
March 2021

Isolation and Characterization of an Acidic, Salt-Tolerant Endoglucanase Cel5A from a Bacterial Strain Martelella endophytica YC6887 Genome.

Mol Biotechnol 2021 Feb 1. Epub 2021 Feb 1.

Division of Applied Life Science (BK21 Plus), Plant Molecular Biology and Biotechnology Research Centre, Gyeongsang National University, 501 Jinju-daero, Jinju, 52828, Republic of Korea.

A Martelella endophytica (M. endophytica) strain YC6887 was previously isolated from the roots of a halophyte, Rosa rugosa, which was sequenced and characterized. The genomic and proteomic analysis showed a carbohydrate-degrading enzyme, endoglucanase Cel5A which was further characterized. The protein analysis revealed that this endoglucanase belongs to glycosidic hydrolase family 5 (GH5) with catalytic domain. This gene encodes 349-residue polypeptide and shows closest similarity with cellulases of other Martelella species. The protein was purified to homogeneity and shown that it was a 39 kDa protein. The purified recombinant Cel5A endoglucanase exhibited maximum activity at 50 °C and pH 4.5. The enzyme was salt tolerant and retained more than 50% residual activity up to 15% NaCl. The homology model structure of Cel5A displayed that it is stable and compact protein structure consisting of eleven α-helical structures and eight β-sheets. According to the predicted ligand binding site after superimposition with Pseudomonas stutzeri endoglucanase Cel5A (PDB ID: 4LX4), it consisted of five amino acid Asn157, Tyr116, Glu158, Glu270 and Trp303 that may be the expected active site of Cel5A from YC6887. This presented that our strain M. endophytica YC6887 that produces cellulase partially degrade the insoluble polysaccharides into reducing sugars.
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http://dx.doi.org/10.1007/s12033-020-00295-3DOI Listing
February 2021

Novel Anticancer Dimeric Napthoquiones from Diospyros lotus Having Anti-Tumor, Anti-Inflammatory and Multidrug Resistance Reversal Potential: In Vitro, In Vivo and In Silico Evidence.

Anticancer Agents Med Chem 2021 Jan 11. Epub 2021 Jan 11.

Natural and Medical Sciences Research Center, University of Nizwa, Birkat-ul-Mouz 616, Nizwa. Oman.

Background: Cancer being a genetically heterogenous and complex disease and the available therapies are not very effective, rendering them the predominant cause of mortality across the world. The discovery of new anticancer drugs with higher efficacy and milder side effects is a great challenge for health professionals.

Objective: The current study focused on anticancer potential of two known dimeric napthoquiones, diospyrin (1) and 8-hydroxydiospyrin (2) isolated from the roots of Diospyros lotus.

Methods: In-vitro Epstein-Barr-Virus (EVA) early antigen activation assay was used to evaluate the antitumor potential of test compounds followed by two-stage carcinogenesis assay on mouse skin for anti-carcinogenic effect. Compounds were also assessed for their multidrug resistance reversal potential. The in-vitro heat induced protein denaturation assay was used for the anti-inflammatory effect of the test compounds.

Results: Both compounds evoked marked cytotoxic activity with IC50 of 47.40 and 36.91 ppm, respectively. In Epstein-Barr-Virus (EVA) early antigen activation assay compounds 1 and 2 showed IC50 values of 426 ppm and 412 ppm, respectively. The tested compounds showed 60% survival rate of the lymphoblastoid Raji cells at a concentration of 1000 (mol / ratio 32 pmol TPA). In two-stage carcinogenesis assay on mouse skin, both compounds significantly delayed the formation of papillomas on mouse skin. Compound 1 showed 50% effect at 14th weeks, whereas compound 2 exerted the same effect at 13th weeks, while both provoked 100% effect at 20th weeks. Both compounds significantly attenuated thermal induced protein denaturation with EC50 values of 298 and 264 µg/mL, respectively. The dimeric napthoquiones were evaluated for their effects on the reversion of multidrug resistant (MDR) cell lines mediated by P-glycoprotein using rhodamine 123 dye-based exclusion screening test on human mdr1 gene transfected thymic lymphoma L5178 cell line. The compounds 1 and 2 exhibited promising MDR reversal effect in a dose-dependent manner against mouse Tlymphoma cell line. Docking results also showed that both compounds have good docking statistics as compared with standard.

Conclusions: Both the compounds demonstrated marked anti-tumor, anti-carcinogenic, and MDR reversal effects with significant attenuation of thermal induced denaturation of protein. These compounds may explain the traditional uses of D. lotus and might be effective anticancer agents.
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http://dx.doi.org/10.2174/1871520621666210112113127DOI Listing
January 2021

Macrocyclic sulfone derivatives: Synthesis, characterization, in vitro biological evaluation and molecular docking.

Drug Dev Res 2020 Dec 23. Epub 2020 Dec 23.

Department of Chemistry, University of Malakand, Chakdara 18800, Dir Lower, Khyber Pakhtunkhwa, Pakistan.

An artificial series of macrocycles based on 4,4'-sulfonyldiphenol intermediate was synthesized using a multistep procedure involving oxidation of bisphenol sulfide, etherification of phenolic hydroxyl groups, and final ring closure with different diamines. Different chemical species having aromatic, heteroaromatic, and aliphatic characters were incorporated into macrocyclic frameworks in the final step of ring closure. This simple and easily executable synthetic strategy was applied to synthesize 15 macrocycles (5a-o) in excellent yields. Characterization of the synthesized products was achieved through well-known modern spectroscopic techniques such as IR, NMR, and Mass. Macrocycles 5m and 5n were found to show significant AChE inhibition with IC values of 76.9 ± 0.24 and 71.2 ± 0.77 μM, respectively. Macrocycle 5n was also found to be an active inhibitor of butyrylcholinesterase (BChE) with IC score of 55.3 ± 0.54 μM. Among others, macrocycle 5l cyclized with o-phenylenediamine demonstrated moderate inhibition with IC value of 81.1 ± 0.54 μM. Increasing interest in studying interactions of macrocycles with different enzymatic targets compelled us to design and synthesize sulfone-based macrocycles that might prove as highly potent class of biologically active compounds.
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http://dx.doi.org/10.1002/ddr.21775DOI Listing
December 2020

Quinazolinones as Competitive Inhibitors of Carbonic Anhydrase-II (Human and Bovine): Synthesis, , Selectivity, and Kinetics Studies.

Front Chem 2020 1;8:598095. Epub 2020 Dec 1.

Natural and Medical Sciences Research Center, University of Nizwa, Nizwa, Oman.

Carbonic anhydrase-II (CA-II) is associated with glaucoma, malignant brain tumors, and renal, gastric, and pancreatic carcinomas and is mainly involved in the regulation of the bicarbonate concentration in the eyes. CA-II inhibitors can be used to reduce the intraocular pressure usually associated with glaucoma. In search of potent CA-II inhibitors, a series of quinazolinones derivatives () were synthesized and characterized by IR and NMR spectroscopy. The inhibitory potential of all the compounds was evaluated against bovine carbonic anhydrase-II (CA-II) and human carbonic anhydrase-II (CA-II), and compounds displayed moderate to significant inhibition with IC values of 8.9-67.3 and 14.0-59.6 μM, respectively. A preliminary structure-activity relationship suggested that the presence of a nitro group on the phenyl ring at R position contributes significantly to the overall activity. Kinetics studies of the most active inhibitor, , against both CA-II and CA-II were performed to investigate the mode of inhibition and to determine the inhibition constants (Ki). According to the kinetics results, is a competitive inhibitor of CA-II and CA-II with Ki values of 13.0 ± 0.013 and 14.25 ± 0.017 μM, respectively. However, the selectivity index reflects that the compounds and are more selective for CA-II. The binding mode of these compounds within the active sites of CA-II and CA-II was investigated by structure-based molecular docking. The docking results are in complete agreement with the experimental findings.
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http://dx.doi.org/10.3389/fchem.2020.598095DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7736042PMC
December 2020

Intense bloom of the diatom Hemidiscus hardmanianus (Greville) in relation to water quality and plankton communities in Tuticorin coast, Gulf of Mannar, India.

Mar Pollut Bull 2021 Feb 30;163:111757. Epub 2020 Nov 30.

Centre of Advanced Study in Marine Biology, Annamalai University, Parangipettai, Tamil Nadu, India.

The present study reports a dense bloom of the marine-diatom Hemidiscus hardmanianus observed off the Tuticorin coast in the Gulf of Mannar (GoM), India. The surface water discoloration (pale green) was observed during a coastal survey conducted in the initial period of the northeast monsoon (October 2018). The bloom extended over an area of approximately 5 km around the Tuticorin harbor. Distribution and relative abundance of the phytoplankton and zooplankton species together with the water quality and Chlorophyll-a were studied in the area of bloom. H. hardmanianus density was maximum (10.57 × 10 cells L) in the bloom site, which was almost 97% of the total phytoplankton population. The present report is the first record of H. hardmanianus bloom in the Gulf of Mannar. The chain-forming diatom Biddulphia biddulphiana was also observed in strong numbers (802 and 432 cells L), which has been rarely reported from the Indian coastal waters.
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http://dx.doi.org/10.1016/j.marpolbul.2020.111757DOI Listing
February 2021

Utilization of the common functional groups in bioactive molecules: Exploring dual inhibitory potential and computational analysis of keto esters against α-glucosidase and carbonic anhydrase-II enzymes.

Int J Biol Macromol 2021 Jan 27;167:233-244. Epub 2020 Nov 27.

Department of Chemistry, Faculty of Natural Sciences, The University of Haripur, Haripur, KPK 22620, Pakistan. Electronic address:

Diabetes mellitus, a progressive chronic disease, characterized by the abnormal carbohydrate metabolism is associated with severe health complications including long term dysfunction or failure of several organs, cardiovascular and micro-angiopathic problems (neuropathy, nephropathy, retinopathy). Despite the existence of diverse chemical structural libraries of α-glucosidase inhibitors, the limited diabetic treatment due to the adverse side effects such as abdominal distention, flatulence, diarrhoea, and liver damage associated with these inhibitors encourage the medicinal research community to design and develop new and potent inhibitors of α-glucosidase with better pharmacokinetic properties. In this perspective, we demonstrate the successful integration of common functional groups (ketone & ester) in one combined pharmacophore which is favorable for the formation of hydrogen bonds and other weaker interactions with the target proteins. These keto ester derivatives were screened for their α-glucosidase inhibition potential and the in vitro results revealed compound 3c as the highly active inhibitor with an IC value of 12.4 ± 0.16 μM compared to acarbose (IC = 942 ± 0.74 μM). This inhibition potency was ~76-fold higher than acarbose. Other potent compounds were 3f (IC = 28.0 ± 0.28 μM), 3h (IC = 33.9 ± 0.09 μM), 3g (IC = 34.1 ± 0.04 μM), and 3d (IC = 76.5 ± 2.0 μM). In addition, the emerging use of carbonic anhydrase inhibitors for the treatment of diabetic retinopathy (a leading cause of vision loss) prompted us to screen the keto ester derivatives for the inhibition of carbonic anhydrase-II. Compound 3b was found significantly active against carbonic anhydrase-II with an IC of 16.5 ± 0.92 μM (acetazolamide; IC = 18.2 ± 1.23 μM). Compound 3a also exhibited comparable potency with an IC value of 18.9 ± 1.08 μM. Several structure-activity relationship analyses depicted the influence of the substitution pattern on both the aromatic rings. Molecular docking analysis revealed the formation of several H-bonding interactions through the ester carbonyl and the nitro oxygens of 3c with the side chains of His348, Arg212 and His279 in the active pocket of α-glucosidase whereas 3b interacted with His95, -OH of Thr197, Thr198 and WAT462 in the active site of carbonic anhydrase-II. Furthermore, evaluation of ADME properties suggests the safer pharmacological profile of the tested derivatives.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.11.170DOI Listing
January 2021

Involvement of selective GABA-A receptor subtypes in amelioration of cisplatin-induced neuropathic pain by 2'-chloro-6-methyl flavone (2'-Cl-6MF).

Naunyn Schmiedebergs Arch Pharmacol 2020 Nov 22. Epub 2020 Nov 22.

Natural and Medical Sciences Research Center, University of Nizwa, Birkat Al Mauz, 616, Nizwa, Oman.

Cisplatin-induced peripheral neuropathic pain is a common adverse effect of chemotherapy. The present study evaluated the effects of 2'-chloro-6-methylflavone (2'-Cl-6MF) at recombinant α1β2γ2L, α2β1-3γ2L, and α3β1-3γ2L GABA-A receptor subtypes expressed in Xenopus oocytes and subsequently evaluated its effectiveness in cisplatin-induced neuropathic pain. The results showed that 2'-Cl-6MF potentiated GABA-elicited currents at α2β2/3γ2L and α3β2/3γ2L GABA-A receptor subtypes. The potentiation was blocked by the co-application of flumazenil (a benzodiazepine (BDZs) site antagonist). In behavioral studies, mechanical allodynia was induced by intraplantar injection of cisplatin (40 μg/paw) in Sprague Dawley rats, and behavioral assessments were made 24 h after injection. 2'-Cl-6MF (1, 10, 30, and 100 mg/kg, i.p.), was administered 1 h before behavioral evaluation. Administration of 2'-Cl-6MF (30 and 100 mg/kg, i.p) significantly enhanced the paw withdrawal threshold and decreased mechanical allodynia. The standard drugs, gabapentin (GBP) at the dose of 70 mg/kg, and HZ 166 (16 mg/kg), i.p. also significantly enhanced the paw withdrawal threshold in mechanical allodynia. Pretreatment with pentylenetetrazole (PTZ) (15 mg/kg, i.p.) and flumazenil reversed the antinociceptive effect of 2'-Cl-6MF in mechanical allodynia indicating GABAergic mechanisms. Moreover, the binding mechanism of 2'-Cl-6MF was rationalized by in silico modeling tools. The 3D-coordinates of α2β2γ2L and α2β3γ2L were generated after homology modeling of the α2 subtype and 2'-Cl-6MF was at predicted binding sites of the developed models. The α2 model was compared with the α1 and α3 subunits via structural and sequence alignment. Molecular docking depicted that the compound binds efficiently at the neuromodulator binding site of the receptors. The findings of this study revealed that 2'-Cl-6MF ameliorated the manifestations of cisplatin-induced neuropathic pain in rats. Furthermore, we also conclude that GABAergic mechanisms may contribute to the antinociceptive effect of 2'-Cl-6MF. The molecular docking studies also confirm the involvement of the BDZs site of GABA-A receptors. It was observed that Ile230 of α2 stabilize the chlorophenyl ring of 2'-Cl-6MF through hydrophobic interactions, which is replaced by Val203 in α1 subunit. However, the smaller side chain of Val203 does not provide hydrophobic interaction to the compound due to high conformational flexibility of α1 subunit.
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http://dx.doi.org/10.1007/s00210-020-02021-xDOI Listing
November 2020

Genetic Spectrum of Syndromic and Non-Syndromic Hearing Loss in Pakistani Families.

Genes (Basel) 2020 Nov 11;11(11). Epub 2020 Nov 11.

Institute of Human Genetics, Julius Maximilians University Würzburg, 97074 Würzburg, Germany.

The current molecular genetic diagnostic rates for hereditary hearing loss (HL) vary considerably according to the population background. Pakistan and other countries with high rates of consanguineous marriages have served as a unique resource for studying rare and novel forms of recessive HL. A combined exome sequencing, bioinformatics analysis, and gene mapping approach for 21 consanguineous Pakistani families revealed 13 pathogenic or likely pathogenic variants in the genes , , , , , , and , with an overall resolve rate of 61.9%. and were the most frequently involved genes in this cohort. All the identified variants were either homozygous or compound heterozygous, with two of them not previously described in the literature (15.4%). Overall, seven missense variants (53.8%), three nonsense variants (23.1%), two frameshift variants (15.4%), and one splice-site variant (7.7%) were observed. Syndromic HL was identified in five (23.8%) of the 21 families studied. This study reflects the extreme genetic heterogeneity observed in HL and expands the spectrum of variants in deafness-associated genes.
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http://dx.doi.org/10.3390/genes11111329DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7709052PMC
November 2020

Bibliometric analysis of road traffic injuries research in the Gulf Cooperation Council region.

F1000Res 2020 18;9:1155. Epub 2020 Sep 18.

Deanship of Library Affairs, Imam Abdulrahman Bin Faisal University, Dammam, Eastern Province, 31441, Saudi Arabia.

Despite governmental interventions, the Gulf Cooperation Council (GCC) region continues to experience higher road traffic crash and fatality rates relative to Western nations. This trend suggests a potential disconnect between Road Traffic Injuries (RTI) research and the mitigation measures put in place. Here, we present an in-depth bibliometric analysis to obtain a comprehensive understanding of RTI research in the GCC region. The Web of Science database was used to search and retrieve the relevant articles during the period of 1981-2019. The volume of RTI research increased from 2015-2019, suggesting an increased focus on traffic safety in the GCC region. Saudi Arabia had the highest RTI research productivity level (126 publications); Bahrain had the lowest (7 publications). Inconsistent with its low publication volume, Hammad Medical Corps of Qatar had the highest citation impact score of 16.33. Global collaboration for RTI research was highest between Saudi Arabia and the United States. The most prevalent publication journal for the region was . The most common keywords were " " and " "; terms such as " ", " ", " ", and " " were least common. In the five most productive GCC nations with respect to RTI research (Saudi Arabia, United Arab Emirates, Qatar, Kuwait, and Oman), researchers tended to publish works related to road traffic safety in traffic safety-oriented journals. The quantity and quality of RTI publications in GCC is insufficient to meet the increasing related public health and economic burden in the region. The trends among publication volumes, citations, and impact were inconsistent. There is a lack of research collaboration among the institutions. Most of the research related to RTI is being conducted by researchers with a medical background. Research focusing on pedestrians, cyclists and road user behavior is also inadequate.
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http://dx.doi.org/10.12688/f1000research.25903.2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7542249PMC
September 2020

Correlation of asthma severity, IgE level, and spirometry results with HRCT findings in allergic bronchopulmonary aspergillosis.

Indian J Radiol Imaging 2020 Apr-Jun;30(2):163-169. Epub 2020 Jul 13.

Department of Radiodiagnosis, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Rae Bareilly Road, Lucknow, Uttar Pradesh, India.

Context: Few studies have been done for correlating asthma severity, IgE level, and spirometry results with high-resolution computed tomographic (HRCT) findings in allergic bronchopulmonary aspergillosis (ABPA).

Aims: This prospective observational study was conducted to correlate asthma severity, IgE level, and spirometry results with HRCT findings in ABPA.

Settings And Design: Prospective observational.

Subjects And Methods: Fifty consecutive adult patients with asthma and positive specific IgE (>0.35 kUA/L) to were recruited from October 2015 to July 2017. Asthma severity, IgE levels, and spirometry results were correlated with HRCT score, bronchiectasis score, air trapping segments, and low-attenuation lung volume on inspiratory CT and expiratory CT.

Statistical Analysis Used: One way ANOVA, Spearman's correlation coefficients.

Results: Asthma severity showed a significant positive correlation with HRCT score and bronchiectasis score. MEF pre and postbronchodilator values showed a significant negative correlation with HRCT score, bronchiectasis score, and percentage expiratory volumes -851 to -950 HU voxels. FEV1 prebronchodilator value showed a significant negative correlation with percentage expiratory volume -851 to -950 HU voxels and percentage expiratory volume -851 to -1024 HU voxels. Specific IgE antibody level showed a significant positive correlation with bronchiectasis score.

Conclusions: Asthma severity, specific IgE level, and MEF values showed a good correlation with HRCT findings. The restrictive pattern is common on spirometry in patients of ABPA. In addition to central bronchiectasis, peripheral bronchial and small airway involvement was an important finding in ABPA. Expiratory HRCT may reveal air trapping in patients having no abnormality on inspiratory CT.
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http://dx.doi.org/10.4103/ijri.IJRI_443_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7546303PMC
July 2020

Impact of Mg level on lattice relaxation in a p-AlGaN hole source layer and attempting excimer laser annealing on p-AlGaN HSL of UVB emitters.

Nanotechnology 2021 Jan;32(5):055702

RIKEN Cluster for Pioneering Research (CPR), 2-1 Hirosawa, Wako, Saitama 351-0198, Japan. RIKEN Center for Advanced Photonics (RAP), 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan.

Mg-doped p-type semiconducting aluminium-gallium-nitride hole source layer (p-AlGaN HSL) materials are quite promising as a source of hole 'p' carriers for the ultraviolet-B (UVB) light-emitting diodes (LEDs) and laser diodes (LDs). However, the p-AlGaN HSL has a central issue of low hole injection due to poor activation of Mg atoms, and the presence of unwanted impurity contamination and the existence of a localized coherent state. Therefore, first the impact of the Mg level on the crystallinity, Al composition and relaxation conditions in the p-AlGaN HSL were studied. An increasing trend in the lattice-relaxation ratios with increasing Mg concentrations in the p-AlGaN HSL were observed. Ultimately, a 40%-60% relaxed and 1.4 μm thick p-AlGaN HSL structure with total threading dislocation densities (total-TDDs) of approximately ∼8-9 × 10 cm was achieved, which almost matches our previous design of a 4 μm thick and 50% relaxed n-AlGaN electron source layer (ESL) with total-TDDs of approximately ∼7-8 × 10 cm. Subsequently, structurally a symmetric p-n junction for UVB emitters was accomplished. Finally, the influence of excimer laser annealing (ELA) on the activation of Mg concentration and on suppression of unwanted impurities as well as on the annihilation of the localized energy state in the p-AlGaN HSL were thoroughly investigated. ELA treatment suggested a reduced Ga-N bonding ratio and increased Ga-O, as well as Ga-Ga bonding ratios in the p-AlGaN HSL. After ELA treatment the localized coherent state was suppressed and, ultimately, the photoluminescence emission efficiency as well as conductivity were drastically improved in the p-AlGaN HSL. By using lightly polarized p-AlGaN HSL assisted by ELA treatment, quite low resistivity in p-type AlGaN HSL at room temperature (hole concentration is ∼2.6 × 10 cm, the hole mobility is ∼9.6 cm V s and the resistivity is ∼24.39 Ω. cm) were reported. ELA treatment has great potential for localized activation of p-AlGaN HSL as well as n- and p-electrodes on n-AlGaN and p-AlGaN contact layers during the flip-chip (FC) process in low operating UVB emitters, including UVB lasers.
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http://dx.doi.org/10.1088/1361-6528/abbddbDOI Listing
January 2021

Photocatalytic Decolorization and Biocidal Applications of Nonmetal Doped TiO: Isotherm, Kinetic Modeling and In Silico Molecular Docking Studies.

Molecules 2020 Sep 29;25(19). Epub 2020 Sep 29.

Department of Environmental Sciences, COMSATS University Islamabad, Abbottabad Campus, Abbottabad 22060, Pakistan.

Textile dyes and microbial contamination of surface water bodies have been recognized as emerging quality concerns around the globe. The simultaneous resolve of such impurities can pave the route for an amicable technological solution. This study reports the photocatalytic performance and the biocidal potential of nitrogen-doped TiO against reactive black 5 (RB5), a double azo dye and . Molecular docking was performed to identify and quantify the interactions of the TiO with β-lactamase enzyme and to predict the biocidal mechanism. The sol-gel technique was employed for the synthesis of different mol% nitrogen-doped TiO. The synthesized photocatalysts were characterized using thermal gravimetric analysis (TGA), scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), Brunauer-Emmett-Teller (BET) and diffuse reflectance spectroscopy (DRS). The effects of different synthesis and reaction parameters were studied. RB5 dye degradation was monitored by tracking shifts in the absorption spectrum and percent chemical oxygen demand (COD) removal. The best nanomaterial depicted 5.57 nm crystallite size, 49.54 m g specific surface area, 11-40 nm particle size with spherical morphologies, and uniform distribution. The RB5 decolorization data fits well with the pseudo-first-order kinetic model, and the maximum monolayer coverage capacity for the Langmuir adsorption model was found to be 40 mg g with K of 0.113 mg. The LH model yielded a higher coefficient K (1.15 mg L h) compared to the adsorption constant K (0.3084 L mg). 90% COD removal was achieved in 60 min of irradiation, confirmed by the disappearance of spectral peaks. The best-optimized photocatalysts showed a noticeable biocidal potential against human pathogenic strain in 150 min. The biocidal mechanism of best-optimized photocatalyst was predicted by molecular docking simulation against β-lactamase enzyme. The docking score (-7.6 kcal mol) and the binding interaction with the active site residues (Lys315, Thr316, and Glu272) of β-lactamase further confirmed that inhibition of β-lactamase could be a most probable mechanism of biocidal activity.
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http://dx.doi.org/10.3390/molecules25194468DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7583793PMC
September 2020

Dual Airway and Esophageal Stenting in Advanced Esophageal Cancer With Lesions Near Carina.

J Bronchology Interv Pulmonol 2020 Oct;27(4):286-293

Departments of Pulmonary Medicine.

Background: Tracheobronchial stenting either alone or with esophageal stenting is often required for symptom palliation in obstructive or fistulous lesions of the airway due to esophageal cancer. There is limited evidence regarding dual stenting for lesions near the carina due to esophageal cancer. Hence, this study aims to evaluate the technical feasibility, outcomes, and complications of preplanned dual stenting in these patients.

Methods: This is a prospective observational study carried out over a period of 4 years (January 2015 to July 2019). All patients undergoing dual stenting in the airway and esophagus with obstructive or fistulous lesions near the carina were included. The esophageal stent was placed within 24 hours. Prestenting and poststenting symptoms were compared using a symptom-based visual analog scale, Hugh Jones dyspnea scale and dysphagia scale.

Results: Twenty-nine patients (20 males; mean±SD age, 55.3±12.2 y) underwent dual stenting. Twenty-four patients had central airway obstruction due to: infiltration in 20 (69%) and external compression in 4 (13.7%), respectively. Five (17.3%) patients had tracheoesophageal fistula with no airway obstruction. In 80% of the patients (n=23), silicone stents were placed. There was significant improvement in both dyspnea and dysphagia after dual stenting (P<0.001). Mucus plugging, lower respiratory infection, and granulation tissue were the main complications. Median survival after dual stent was 97 days (range, 17 to 297 d).

Conclusion: Dual stenting within the airway and the esophagus is a safe and viable option for palliative relief of symptoms in patients with advanced esophageal cancer.
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http://dx.doi.org/10.1097/LBR.0000000000000672DOI Listing
October 2020

A novel noble-metal-free MoC-InS heterojunction photocatalyst with efficient charge separation for enhanced photocatalytic H evolution under visible light.

J Colloid Interface Sci 2021 Jan 28;582(Pt B):488-495. Epub 2020 Aug 28.

Beijing Key Laboratory for Science and Application of Functional Molecular and Crystalline Materials, University of Science and Technology Beijing, Beijing 100083, China.

Currently, designing novel noble-metal-free photocatalysts with efficient carriers migration and catalytically active sites have been a researching hotspot in photocatalytic hydrogen evolution. In this paper, a novel noble-metal-free MoC-InS heterojunction was synthesized by a simple hydrothermal method. Morphology characterization revealed InS was attached to MoC. Electrochemical results showed MoC improved the interface conductivity, and promoted the transportation of photogenerated carriers. Under visible light, the optimal MoC-InS composite achieved a H generation rate of 535.58 μmol h g, which was 175.6 and 25.8 times higher than pristine InS (3.05 μmol h g) and InS-1% Pt (20.73 μmol h g). In addition, a reasonable mechanism of the elevated photocatalytic activity was also discussed. This study demonstrates commercial MoC has an important effect of separating carriers and replacing Pt as co-catalyst in heterojunctions. This research also provides a method to design and synthesize new noble-metal-free photocatalysts for excellent hydrogen production activity.
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http://dx.doi.org/10.1016/j.jcis.2020.08.083DOI Listing
January 2021

New multitarget directed benzimidazole-2-thiol-based heterocycles as prospective anti-radical and anti-Alzheimer's agents.

Drug Dev Res 2020 Sep 8. Epub 2020 Sep 8.

Department of Chemistry, University of Malakand, Chakdara, Khyber Pakhtunkhwa, Pakistan.

A series of new heterocycles (4-18) was synthesized by the structural modification of benzimidazole-2-thiol (BT, 2-MBI). The structures of the synthesized compounds were confirmed with the help of high-resolution mass spectrometry (HRMS) and HNMR spectroscopy. High inhibitions of the oxidants such as ABTS and DPPH were observed for compounds 9 [IC (s) = 167.4 μM (ABTS), 139.5 μM (DPPH)], 10 [IC (s) = 186.5 μM (ABTS), 155.4 μM (DPPH)], 11 [IC (s) = 286.1 μM (ABTS), 189.1 μM (DPPH)], 12 [IC (s) = 310.8 μM (ABTS), 162.2 μM (DPPH)], 14 [IC (s) = 281.3 μM (ABTS), 205.7 μM (DPPH)], 15 [IC (s) = 284.1 μM (ABTS), 177.3 μM (DPPH)], and 16 [IC (s) = 344.7 μM (ABTS), 270.2 μM (DPPH)] as compared with Ascorbic acid [IC (s) = 340.9 μM (ABTS), 164.3 μM (DPPH)]. The anti-Alzheimer's activity was performed in vitro against cholinesterase enzymes (AChE, BChE). Compound 11 was able to show significant inhibitions [IC (s) = 121.2 μM (AChE), 38.3 μM (BChE)] as against that of galantamine [IC (s) = 139.4 μM (AChE), 40.3 μM (BChE)]. Compound 14 was found as a very good inhibitor of butyrylcholinesterase (IC = 35.4 μM) as compared with standard galantamine. Molecular docking was further performed to investigate the mechanism of anticholinesterase activity.
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http://dx.doi.org/10.1002/ddr.21740DOI Listing
September 2020

Biomonitoring of DNA Damage in Photocopiers' Workers From Peshawar, Khyber Pakhtunkhwa, Pakistan.

J Occup Environ Med 2020 Sep;62(9):e527-e530

Department of Zoology, University of Peshawar, Khyber Pakhtunkhwa, Pakistan.

Objectives: The study was performed to know about the extent of occupational DNA damage in photocopiers' workers.

Methods: Blood samples were collected from 136 exposed group and 74 control group. Comet assay was performed to assess the DNA damage caused by emissions from photocopiers.

Results: The results indicated that there was a significant increase (P < 0.05) in DNA damage in persons working in photocopiers (122.1 ± 60.7) than the controls (56.6 ± 17.2). Duration of occupational exposure had positive correlation (r = 0.793, P < 0.001) with DNA damage. Age had significant effects on the total comet score (TCS) of the exposed group as compared to the control group (P < 0.05).

Conclusions: In conclusion, these findings indicate significant genotoxicity in photocopiers' workers.
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http://dx.doi.org/10.1097/JOM.0000000000001964DOI Listing
September 2020

Green synthesis of silver and gold nanoparticles using Crataegus oxyacantha extract and their urease inhibitory activities.

Biotechnol Appl Biochem 2020 Sep 4. Epub 2020 Sep 4.

Department of Chemistry, University of Malakand, Khyber Pakhtunkhwa, 18800, Pakistan.

This study reports the green synthesis and urease inhibitory activities of Ag and Au nanoparticles (NPs) using Crataegus oxyacantha extract. The synthesized NPs were characterized by UV-visible, FT-IR spectroscopy, atomic force microscopy, and scanning electron microscopy. The obtained NPs were spherical in shape, and their size was around 85 nm. A strong correlation between the phytochemicals present in the extract and their capability for the synthesis of NPs was observed. Furthermore, the shape, size, stability, and bioactivity of the NPs were strongly influenced by the stabilizing phytochemicals. The experimental analysis suggested that these NPs have substantial stability in a diverse range of physiological conditions such as pH, salinity, and temperature. The NPs exhibited potent urease enzyme inhibitory activities with percent inhibition of 99.25 and IC value of 1.38 ± 0.3, comparable to the standard (thiourea percent inhibition, that is, 98.2% and IC value 5.3 ± 0.04). These results suggested that the proposed NPs could be used in the homeopathic and pharmaceutical industries for biomedical applications.
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http://dx.doi.org/10.1002/bab.2018DOI Listing
September 2020

Tungsten-Catalyzed Allylic Substitution with a Heteroatom Nucleophile: Reaction Development and Synthetic Applications.

J Org Chem 2020 09 25;85(17):11501-11510. Epub 2020 Aug 25.

Department of Applied Chemistry, School of Science and Xi'an Key Laboratory of Sustainable Energy Material Chemistry, Xi'an Jiao Tong University, Xi'an 710049, P. R. China.

A tungsten-catalyzed allylic allylation of sodium sulfinate as the heteroatom nucleophile was developed. The reaction utilizes inexpensive and readily available (CHCN)W(CO) as a precatalyst and proceeds at 60 °C temperature in the presence of 2,2'-bipyridine and its derivatives as ligand. The synthetic utility of allylic sulfones as electrophile was further demonstrated through Suzuki-Miyaura cross-coupling as showcased by the formal synthesis of (±)-hinokiresinol.
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http://dx.doi.org/10.1021/acs.joc.0c01632DOI Listing
September 2020

Polymorphism in GSTM1 and GSTT1 genes influence DNA damage in personnel occupationally exposed to volatile anaesthetics (VA), from Peshawar, Pakistan.

Occup Environ Med 2020 11 27;77(11):769-774. Epub 2020 Jul 27.

Khyber College of Dentistry, Khyber Medical University, Peshawar, Pakistan.

Objectives: The objective of this study was to assess the influence of antioxidant gene GSTM1 and GSTT1 on DNA damage in personnel occupationally exposed to volatile anaesthetics (VA).

Methods: The study groups were composed of 50 exposed subjects (anaesthesia workers) and 49 controls. Blood samples were collected from both subjects. DNA damage was analysed through the comet assay technique. Biomarker genes GSTM1 and GSTT1 were inspected through PCR technique for polymorphism.

Results: The comet assay technique showed that the Total Comet Score (TCS) in exposed subjects was significantly higher (p=0.0001) than the control. Age and smoking had significant effects on TCS in the study groups (p<0.05). Duration of occupational exposure had significant positive correlation (r=0.755, p<0.001) with DNA damage. The null polymorphism in GSTM1 and GSTT1 gene showed a significant effect (p<0.001 and p<0.000) on the DNA damage.

Conclusions: The polymorphism in GSTM1 and GSTT1 gene significantly damage DNA in personnel occupationally exposed to VA.
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http://dx.doi.org/10.1136/oemed-2020-106561DOI Listing
November 2020

In silico data mining of large-scale databases for the virtual screening of human interleukin-2 inhibitors.

Acta Pharm 2021 Mar;71(1):33-56

Natural and Medical Science Research Center, University of Nizwa Birkat-ul-Mouz 616, Nizwa Sultanate of Oman.

Interleukin-2 (IL-2) is involved in the activation and differentiation of T-helper cells. Uncontrolled activated T cells play a key role in the pathophysiology by stimulating inflammation and autoimmune diseases like arthritis, psoriasis and Crohn's disease. T cells activation can be suppressed either by preventing IL-2 production or blocking the IL-2 interaction with its receptor. Hence, IL-2 is now emerging as a target for novel therapeutic approaches in several autoimmune disorders. This study was carried out to set up an effective virtual screening (VS) pipeline for IL-2. Four docking/scoring approaches (FRED, MOE, GOLD and Surflex-Dock) were compared in the re-docking process to test their performance in producing correct binding modes of IL-2 inhibitors. Surflex-Dock and FRED were the best in predicting the native pose in its top-ranking position. Shapegauss and CGO scoring functions identified the known inhibitors of IL-2 in top 1, 5 and 10 % of library and differentiated binders from non-binders efficiently with average AUC of > 0.9 and > 0.7, resp. The applied docking protocol served as a basis for the VS of a large database that will lead to the identification of more active compounds against IL-2.
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http://dx.doi.org/10.2478/acph-2021-0002DOI Listing
March 2021

Scalp Hair Metal Analysis Concerning DNA Damage in Welders of Peshawar Khyber Pakhtunkhwa Pakistan.

Biol Trace Elem Res 2020 Jul 16. Epub 2020 Jul 16.

Department of Zoology, University of Peshawar, Peshawar, Khyber Pakhtunkhwa, 25120, Pakistan.

Welding is used throughout the world in refineries, thermal power plants, chemical facilities, and pressurized containers, and the welders are exposed to toxic heavy metals, electromagnetic fields, polycyclic aromatic hydrocarbon, and ultraviolet radiations. In the present study, 59 welders and an equal number of control subjects were assessed for DNA damage in the lymphocytes using the comet assay. Heavy metals such as lead (Pb), iron (Fe), nickel (Ni), chromium (Cr), manganese (Mn), and cadmium (Cd) levels in the scalp hair of the subjects were evaluated by using atomic absorption spectroscopy (AAS). The results of the current study showed that DNA damage in the lymphocytes of welders (121.8 ± 10.7) was significantly higher as compared with controls (56.5 ± 17.6) (P < 0.001). Besides, the levels of Pb, Fe, Ni, Cr, Mn, and Cd were remarkably higher in the scalp hair of workers as compared with the control group (P < 0.001). Regression analysis showed a prominent association between the heavy metals and total comet score (TCS) in the exposed subjects. Age and duration of occupational exposure had significant effects (P < 0.05) on TCS values. Our results concluded that occupational exposure to welding fumes may cause DNA damage and can lead to important health hazards in the workers.
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http://dx.doi.org/10.1007/s12011-020-02281-xDOI Listing
July 2020

Diterpenoids and Triterpenoids From Frankincense Are Excellent Anti-psoriatic Agents: An Approach.

Front Chem 2020 25;8:486. Epub 2020 Jun 25.

Natural and Medical Sciences Research Center, University of Nizwa, Nizwa, Oman.

Psoriasis is a chronic autoimmune disease that affects 2-3% of the global population and requires an effective treatment. Frankincense has been long known for its potent anti-inflammatory activities. In this study, a structural bioinformatics approach was used to evaluate the efficacy of individual active components of frankincense, macrocyclic diterpenoid derivatives (-), and boswellic acids (-) in the treatment of psoriasis. Initially, major druggable targets of psoriasis were identified. Subsequently, structure-based screening was employed by using three different docking algorithms and scoring functions (MOE, AutoDock Vina, and MVD) for the target fishing of compounds against 18 possible targets of psoriasis. Janus Kinase 1, 2, 3 (JAK 1/2/3), eNOS, iNOS, interleukin-17 (IL-17), and Tumor necrosis factor-α (TNF-α) were identified as the preferred molecular targets for these compounds. This computational analysis reflects that frankincense diterpenoids and triterpenoids can serve as excellent anti-psoriatic agents by targeting major cytokines (TNF-α, IL-17, IL-13, IL-23, and IL-36γ,) exacerbated in psoriasis, and inflammatory pathways particularly JAK1/2/3, eNOS, iNOS, MAPK2, and IFNγ. The results were compared with the reported experimental findings which correlates well with our verdicts.
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http://dx.doi.org/10.3389/fchem.2020.00486DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7330179PMC
June 2020

DNA damage analysis concerning GSTM1 and GSTT1 gene polymorphism in gold jewellery workers from Peshawar Pakistan.

Biomarkers 2020 Sep 12;25(6):483-489. Epub 2020 Jul 12.

Department of Zoology, University of Peshawar, Peshawar, Pakistan.

Purpose: To evaluate the genotoxic effects of gold jewellery fumes and its association with GSTM1 and GSTT1 genetic polymorphisms.

Materials And Methods: We examined 94 subjects including 54 gold jewellery workers and 40 controls. The DNA damage was evaluated by alkaline comet assay and genotyping by PCR.

Results: The mean total comet score (TCS) in gold jewellery workers was significantly higher as compared to the control subjects (128.0 ± 60.6 versus 47.7 ± 21.4;  = 0.0001). Duration of occupational exposure had positive correlation ( = 0.453,  < 0.01) with DNA damage. Age and tobacco use had significant effects on the TCS of the exposed group as compared to the control group ( < 0.05). The frequency of the GSTM1-null genotype in the exposed group was significant ( = 0.004) as compared to the control group. No significant association ( > 0.05) between the GSTM1 and GSTT1 genotypes and DNA damage was found.

Conclusions: Our results suggest that there is increased DNA damage in gold jewellery workers due to their occupational surroundings. Hence there is a strong need to educate the workers about the adverse health effects of potentially hazardous chemicals and highlight the importance of using protective measures.
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http://dx.doi.org/10.1080/1354750X.2020.1791253DOI Listing
September 2020

Prevalence of p-glycoprotein (PGP) expression, function and its effect on efficacy of rifampicin in patients with lymph node tuberculosis.

Indian J Tuberc 2020 Apr 3;67(2):172-176. Epub 2019 Dec 3.

Department of Pulmonary Medicine, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Raebareilly Road, Lucknow, 226014, India. Electronic address:

Objective: P-glycoprotein (PGP) overexpression may be one of the operating mechanisms of suboptimal responses to antitubercular treatment (ATT) in patients with lymph node tuberculosis. This might become responsible for the development of drug resistance later due to exposure of subtherapeutic concentrations to the mycobacteria. In this study we aim to study the prevalence of PGP expression and function and its relationship with serum concentrations of Rifampicin in consecutive patients with lymph node tuberculosis.

Methods: All newly diagnosed treatment naïve subjects with a confirmed diagnosis of tubercular lymphadenopathy were included in the study and the expression and function of PGP in blood was determined by flowcytometry at baseline and after two months of treatment. Serum levels of Rifampicin was measured at 2 months by high performance liquid chromatography (HPLC). The mean net PGP expression expressed as percent and relative fluorescence indices (RFI) of PGP expression and function respectively was compared at baseline at 2 months and was also correlated with serum rifampicin levels.

Results: The mean net PGP expression, RFI of PGP expression and RFI of PGP function were significantly higher in patients with lymph node tuberculosis as compared to healthy controls and the mean net PGP expression and RFI of PGP expression were significantly higher at 2 months as compared to baseline (25.64 ± 5.18% vs. 27.68 ± 4.89%, 4.34 ± 1.09% vs. 4.95 ± 1.55). There was no significant difference in RFI of PGP expression and RFI of PGP function between the poor-responders and responders at baseline and 2 months however there was a trend towards significantly higher net PGP expression amongst poor responders at baseline. The mean serum rifampicin levels were 10.74 ± 2.36 μg/ml in the responder group and 7.86 ± 1.21 μg/ml in the non-responder group and the difference between the two was statistically significant (p = 0.004).

Conclusions: Overexpression of PGP is common in patients with lymph node tuberculosis and leads to lower concentrations of Rifampicin in blood which subsequently may give rise to development of drug resistance. This is also responsible for poor therapeutic responses in these patients. Nonspecific inhibitors of PGP may be used in conjunction with ATT to augment therapeutic response in such cases.
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http://dx.doi.org/10.1016/j.ijtb.2019.11.015DOI Listing
April 2020

Diabetes conversation map - a novel tool for diabetes management self-efficacy among type 2 diabetes patients in Pakistan: a randomized controlled trial.

BMC Endocr Disord 2020 Jun 16;20(1):88. Epub 2020 Jun 16.

Indus college of Allied Health, The Indus Hospital, Karachi, Pakistan.

Background: This study aimed to measure the effect of diabetes education using the novel method of "diabetes conversation map (DCM)" as compared to routine counselling (RC) on diabetes management self-efficacy (DMSE) among patients living with type 2 diabetes in Karachi, Pakistan.

Methods: A parallel arm randomized controlled trial among patients with type 2 diabetes aged 30-60 years, with HbA1c > 7%, diagnosed for at least 5 yrs., was conducted at the national institute of diabetes and endocrinology in Karachi, Pakistan. A total 123 type 2 diabetes patients were randomized into DCM (n = 62) or RC (n = 61). Four weekly diabetes control sessions of 40 min each using the DCM or RC was provided. DMSE was measured using a validated Urdu language DMSE tool at baseline and after three months of the randomization. Change in DMSE and HbA1c levels within groups (pre-post) and between the groups after 3 months of enrollment was compared.

Results: Baseline characteristics except HbA1c were similar between the two arms. After 3 months of enrollment, there was no change in the DMSE score in the RC arm however, significant increase in DMSE score was noted in the DCM arm (P = < 0.001). The average difference (95% confidence interval) in DMSE score between the DCM and RC arm was 33.7(27.3, 40.0; p = < 0.001) after 3 months of the enrollment. Difference in HbA1c within groups was not significant.

Conclusions: DCM significantly improved DMSE among type 2 diabetes patients in a developing country setting like Pakistan. Healthcare workers caring for type 2 diabetes patients need to be trained on DCM to effectively utilize this novel tool for educating diabetes patients.

Trial Registration: This trial was prospectively registered. ClinicalTrials.gov Identifier: NCT03747471. Date of registration: Nov 20. 2018.
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http://dx.doi.org/10.1186/s12902-020-00572-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7298747PMC
June 2020