MyMedR

Displaying publications 1 - 20 of 34 in total

Abstract:

Sort:

Molecular Cloning, Expression, Sequence Characterization and Structural Insight of Bubalus bubalis Growth Hormone-Receptor

Gul R, Hanif MU, Gul F, Rehman HM, Saleem M, Ahmad MS, et al.

Mol Biotechnol, 2023 Jul;65(7):1062-1075.
PMID: 36437440 DOI: 10.1007/s12033-022-00612-y

The current study focuses on molecular cloning, expression and structural characterization of growth hormone-receptor (GHR) and its extracellular domain as growth hormone binding protein (GHBP) from the liver of Nili-Ravi buffalo (Bubalus bubalis; Bb). RNA was isolated, genes were amplified by reverse transcriptase-polymerase chain reaction and sequence was characterized. The BbGHR sequence showed three amino acid variations in the extracellular domain when compared with Indian BbGHR. For the production of full length BbGHR and BbGHBP in Escherichia coli (E. coli) BL21 (RIPL) Codon Plus, expression plasmids were constructed under the control of T7lac promoter and isopropyl β-D thiogalactopyranoside was used as an inducer. BbGHR and BbGHBP were expressed as inclusion bodies at ~ 40% and > 30% of the total E. coli proteins, respectively. The BbGHBP was solubilized and refolded by dilution method using cysteine-cystine redox potential. The recombinant BbGHBP was purified and biological activity was checked on HeLa cell lines showing increase cell proliferation in the presence of ovine GH (oGH), hence justifying the increase in the half-life of GH in the presence of BbGHBP. For the molecular interactions of oGH-BbGHBP multiple docking programs were employed to explore the subsequent interactions which showed high binding affinity and presence of large number of hydrogen bonds. Molecular Dynamics studies performed to examine the stability of proteins and exhibited stable structures along with favorable molecular interactions. This study has described the sequence characterization of BbGHR in Nili-Ravi buffaloes and hence provided the basis for the assessment of GH-GHR binding in other Bovidae species.
Indications, preferences, global practice patterns and outcomes in retrograde intrarenal surgery (RIRS) for renal stones in adults: results from a multicenter database of 6669 patients of the global FLEXible ureteroscopy Outcomes Registry (FLEXOR)

Gauhar V, Chew BH, Traxer O, Tailly T, Emiliani E, Inoue T, et al.

World J Urol, 2023 Feb;41(2):567-574.
PMID: 36536170 DOI: 10.1007/s00345-022-04257-z

PURPOSE: To collect a multicentric database on behalf of TOWER research group to assess practice patterns and outcomes of retrograde intrarenal surgery (RIRS) for kidney stones.
METHODS: Inclusion criteria: age ≥ 18 years, normal renal/calyceal system anatomy, calculi of any size, number, and position.
STUDY PERIOD: January 2018 and August 2021. Stone-free status: absence of fragments > 2 mm, assessed post procedure according to the local protocol (KUB X-Ray and/or ultrasound or non-contrast CT scan).
RESULTS: Twenty centers from fifteen countries enrolled 6669 patients. There were 4407 (66.2%) men. Mean age was 49.3 ± 15.59 years. Pain was the most frequent symptom indication for intervention (62.6%). 679 (10.2%) patients underwent RIRS for an incidental finding of stones. 2732 (41.0%) patients had multiple stones. Mean stone size was 10.04 ± 6.84 mm. A reusable flexible ureteroscope was used in 4803 (72.0%) procedures. A sheath-less RIRS was performed in 454 (6.8%) cases. Holmium:YAG laser was used in 4878 (73.1%) cases. A combination of dusting and fragmentation was the most common lithotripsy mode performed (64.3%). Mean operation time was 62.40 ± 17.76 min. 119 (1.8%) patients had an intraoperative injury of the ureter due to UAS insertion. Mean postoperative stay was 3.62 ± 3.47 days. At least one postoperative complication occurred in 535 (8.0%) patients. Sepsis requiring intensive care admission occurred in 84 (1.3%) patients. Residual fragments were detected in 1445 (21.7%) patients. Among the latter, 744 (51.5%) patients required a further intervention.
CONCLUSION: Our database contributes real-world data to support to a better understanding of modern RIRS practice and outcomes.
Diospyros malabarica (Desr.) Kostel fruits extract attenuated acute and chronic inflammation through modulation of the expression of pro- and anti-inflammatory biomarkers in rat models

Zia S, Saleem M, Asif M, Hussain K, Butt BZ

Inflammopharmacology, 2022 Dec;30(6):2211-2227.
PMID: 36223063 DOI: 10.1007/s10787-022-01048-1

Rheumatoid arthritis is a chronic inflammatory disorder of polyarticular tissues, characterised by progressive synovitis. Its prolonged treatment imparts a huge burden on the healthcare system and results in toxicity, which necessitates the search for safe, efficacious and cost-effective therapies. Diospyros malabarica (Desr.) Kostel is traditionally used for anti-inflammatory purposes; however, to the best of our knowledge, there is no detailed study reporting the in vivo anti-inflammatory potential of this plant. Therefore, in the current study, the methanol extract of D. malabarica (Desr.) Kostel fruit (mDMF) was evaluated for its antioxidant, anti-inflammatory and anti-arthritic potentials, along with its underlying mechanisms. The antioxidant activity was evaluated by DPPH assay. Total phenolic and flavonoid contents were estimated via colorimetric and high-performance liquid chromatography (HPLC) methods. Different doses (250, 500 and 750 mg/kg) of mDMF were used to evaluate the anti-inflammatory and anti-arthritis actions in acute inflammatory (carrageenan and histamine-induced paw oedema) and Freund's complete adjuvant (FCA)-induced arthritis rat models. Levels of various pro- and anti-inflammatory biomarkers were estimated using ELISA and RT-PCR techniques. Paw samples were used for different histopathological and radiographic studies. Qualitative phytochemical and HPLC analyses indicated the presence of various polyphenolic compounds in mDMF, which exhibited marked antioxidant activity in the DPPH assay. mDMF showed time-dependent anti-inflammatory and anti-arthritic effects in in vivo models. ELISA assay data showed significant (p
Fulltext Therapeutic Potential of Standardized Extract of Melilotus indicus (L.) All. and Its Phytochemicals against Skin Cancer in Animal Model: In Vitro, In Vivo, and In Silico Studies

Bashir A, Asif M, Saadullah M, Saleem M, Khalid SH, Hussain L, et al.

ACS Omega, 2022 Jul 26;7(29):25772-25782.
PMID: 35910099 DOI: 10.1021/acsomega.2c03053

Melilotus indicus (L.) All. is known to have anti-inflammatory and anticancer properties. The present study explored the in vivo skin carcinogenesis attenuating potential of ethanolic extract of M. indicus (L.) All. (Miet) in a 7,12-dimethylbenz[a]anthracene (DMBA)-induced skin cancer model. The ethanolic extract of the plant was prepared by a maceration method. HPLC analysis indicated the presence of quercetin in abundance and also various other phytoconstituents. DPPH radical scavenging assay results showed moderate antioxidant potential (IC50 = 93.55 ± 5.59 μg/mL). A topical acute skin irritation study showed the nonirritant nature of Miet. Data for the skin carcinogenic model showed marked improvement in skin architecture in Miet and its primary phytochemicals (quercetin and coumarin) treated groups. Miet 50% showed comparable effects with 5-fluorouracil. Significant (p < 0.05) anticancerous effects were seen in coumarin-quercetin combination-treated animals than in single agent (coumarin and quercetin alone)-treated animals. Chorioallantoic membrane (CAM) assay results showed the antiangiogenic potential of Miet. Treatment with Miet significantly down-regulated the serum levels of CEA (carcinoembryonic antigen) and TNF-α (Tumor necrosis factor-α). Data for the docking study indicated the binding potential of quercetin and coumarin with TNF-α, EGFR, VEGF, and BCL2 proteins. Thus, it is concluded that Miet has skin cancer attenuating potential that is proposed to be due to the synergistic actions of its bioactive molecules. Further studies to explore the effects of Miet and its bioactive molecules as an adjuvant therapy with low dose anticancer drugs are warranted, which may lead to a new area of research.
Raphanus sativus Seeds Oil Arrested in vivo Inflammation and Angiogenesis through Down-regulation of TNF-α

Asif M, Yousaf HM, Saleem M, Hussain L, Mahrukh, Zarzour RA, et al.

Curr Pharm Biotechnol, 2022;23(5):728-739.
PMID: 34225619 DOI: 10.2174/1389201022666210702120956

BACKGROUND: Raphanus sativus is traditionally used as an anti-inflammatory agent.
OBJECTIVES: The current study was designed to explore the in vivo anti-inflammatory and antiangiogenic properties of Raphanus sativus seeds oil.
METHODS: Cold press method was used for the extraction of oil (RsSO) and was characterised by using GC-MS techniques. Three in vitro antioxidant assays (DPPH, ABTS and FRAP) were performed to explore the antioxidant potential of RsSO. Disc diffusion methods were used to study in vitro antimicrobial properties. In vivo anti-inflammatory properties were studied in both acute and chronic inflammation models. In vivo chicken chorioallantoic membrane assay was performed to study antiangiogenic effects. Molecular mechanisms were identified using TNF-α ELISA kit and docking tools.
RESULTS: GC-MS analysis of RsSO revealed the presence of hexadecanoic and octadecanoic acid. Findings of DPPH, ABTS, and FRAP models indicated relatively moderate radical scavenging properties of RsSO. Oil showed antimicrobial activity against a variety of bacterial and fungal strains tested. Data of inflammation models showed significant (p < 0.05) anti-inflammatory effects of RsSO in both acute and chronic models. 500 mg/kg RsSO halted inflammation development significantly better (p < 0.05) as compared with lower doses. Histopathological evaluations of paws showed minimal infiltration of inflammatory cells in RsSO-treated animals. Findings of TNF-α ELSIA and docking studies showed that RsSO has the potential to down-regulate the expression of TNF-α, iNOS, ROS, and NF-κB respectively. Moreover, RsSO showed in vivo antiangiogenic effects.
CONCLUSION: Data of the current study highlight that Raphanus sativus seeds oil has anti-inflammatory, and antiangiogenic properties and can be used as an adjunct to standard NSAIDs therapy which may reduce the dose and related side effects.
Fulltext Combined 3D-QSAR, molecular docking and dynamics simulations studies to model and design TTK inhibitors

Ashraf N, Asari A, Yousaf N, Ahmad M, Ahmed M, Faisal A, et al.

Front Chem, 2022;10:1003816.
PMID: 36405310 DOI: 10.3389/fchem.2022.1003816

Tyrosine threonine kinase (TTK) is the key component of the spindle assembly checkpoint (SAC) that ensures correct attachment of chromosomes to the mitotic spindle and thereby their precise segregation into daughter cells by phosphorylating specific substrate proteins. The overexpression of TTK has been associated with various human malignancies, including breast, colorectal and thyroid carcinomas. TTK has been validated as a target for drug development, and several TTK inhibitors have been discovered. In this study, ligand and structure-based alignment as well as various partial charge models were used to perform 3D-QSAR modelling on 1H-Pyrrolo[3,2-c] pyridine core containing reported inhibitors of TTK protein using the comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) approaches to design better active compounds. Different statistical methods i.e., correlation coefficient of non-cross validation (r2), correlation coefficient of leave-one-out cross-validation (q2), Fisher's test (F) and bootstrapping were used to validate the developed models. Out of several charge models and alignment-based approaches, Merck Molecular Force Field (MMFF94) charges using structure-based alignment yielded highly predictive CoMFA (q2 = 0.583, Predr2 = 0.751) and CoMSIA (q2 = 0.690, Predr2 = 0.767) models. The models exhibited that electrostatic, steric, HBA, HBD, and hydrophobic fields play a key role in structure activity relationship of these compounds. Using the contour maps information of the best predictive model, new compounds were designed and docked at the TTK active site to predict their plausible binding modes. The structural stability of the TTK complexes with new compounds was confirmed using MD simulations. The simulation studies revealed that all compounds formed stable complexes. Similarly, MM/PBSA method based free energy calculations showed that these compounds bind with reasonably good affinity to the TTK protein. Overall molecular modelling results suggest that newly designed compounds can act as lead compounds for the optimization of TTK inhibitors.
Fulltext Molecular and hematological studies in a cohort of beta zero South East Asia deletion (β°-thal SEA) from Malaysian perspective

Yasin NM, Abdul Hamid FS, Hassan S, Sudin A, Yassim H, Mohd Sahid EN, et al.

Front Pediatr, 2022;10:974496.
PMID: 36533237 DOI: 10.3389/fped.2022.974496

ABSTRACT: We report the haematological parameters and molecular characterization of beta zero (β°) South East Asia (SEA) deletion in the HBB gene cluster with unusually high levels of Hb F compared to a classical heterozygous beta zero (β°)-thalassaemia.
METHODS: Retrospective study on 17 cases of (β°) South East Asia (SEA) deletion from 2016 to 2019 referred to Institute for Medical Research were conducted. The clinical information and haematological profiles were evaluated. The mutation was analyzed, and the results were compared with other β°-thalassaemia groups. For HBB gene genotyping, all the cases were subjected for multiplex gap-PCR, 5 cases were subjected for HBB gene sequencing for exclusion of compound heterozygous with other beta variants. Co-inheritance of α-thalassaemia were determined using multiplex gap-PCR and multiplex ARMS-PCR.
RESULTS: Seventeen cases were positive for β°-thal SEA deletion. Fifteen cases were heterozygous and two were compound heterozygous for β°-thal SEA deletion. The results were compared with 182 cases of various heterozygous β° deletions and mutations. The mean Hb for heterozygous β°-thal SEA deletion (13.44 ± 1.45 g/dl) was normal and significantly higher than heterozygous IVS 1-1 and Codon 41/42 (post hoc test, p
Fulltext Potential role of marine species-derived bioactive agents in the management of SARS-CoV-2 infection

Asif M, Saleem M, Yaseen HS, Yehya AH, Saadullah M, Zubair HM, et al.

Future Microbiol, 2021 Nov;16(16):1289-1301.
PMID: 34689597 DOI: 10.2217/fmb-2021-0024

COVID-19, caused by the SARS-CoV-2 outbreak, has resulted in a massive global health crisis. Bioactive molecules extracted or synthesized using starting material obtained from marine species, including griffithsin, plitidepsin and fingolimod are in clinical trials to evaluate their anti-SARS-CoV-2 and anti-HIV efficacies. The current review highlights the anti-SARS-CoV-2 potential of marine-derived phytochemicals explored using in silico, in vitro and in vivo models. The current literature suggests that these molecules have the potential to bind with various key drug targets of SARS-CoV-2. In addition, many of these agents have anti-inflammatory and immunomodulatory potentials and thus could play a role in the attenuation of COVID-19 complications. Overall, these agents may play a role in the management of COVID-19, but further preclinical and clinical studies are still required to establish their role in the mitigation of the current viral pandemic.
Fulltext Invasive Weed Asystasia gangetica as a Potential Biomonitor and a Phytoremediator of Potentially Toxic Metals: A Case Study in Peninsular Malaysia

Yap CK, Chew W, Al-Mutairi KA, Al-Shami SA, Nulit R, Ibrahim MH, et al.

Int J Environ Res Public Health, 2021 04 28;18(9).
PMID: 33924835 DOI: 10.3390/ijerph18094682

The invasive weed Asystasia gangetica was investigated for its potential as a biomonitor and as a phytoremediator of potentially toxic metals (PTMs) (Cd, Cu, Ni, Pb, and Zn) in Peninsular Malaysia owing to its ecological resistance towards unfavourable environments. The biomonitoring potential of PTMs was determined based on the correlation analysis of the metals in the different parts of the plant (leaves, stems, and roots) and its habitat topsoils. In the roots, the concentrations (mg/kg dry weight) of Cd, Cu, Ni, Pb, and Zn ranged from 0.03 to 2.18, 9.22 to 139, 0.63 to 5.47, 2.43 to 10.5, and 50.7 to 300, respectively. In the leaves, the concentrations (mg/kg dry weight) of Cd, Cu, Ni, Pb, and Zn ranged from 0.03 to 1.16, 7.94 to 20.2, 0.03 to 6.13, 2.10 to 21.8, and 18.8 to 160, respectively. In the stems, the concentrations (mg/kg dry weight) of Cd, Cu, Ni, Pb, and Zn ranged from 0.03 to 1.25, 5.57 to 11.8, 0.23 to 3.69, 0.01 to 7.79, and 26.4 to 246, respectively. On the other hand, the phytoremediation potential of the five metals was estimated based on the bioconcentration factor (BCF) and the translocation factor (TF) values. Correlation analysis revealed that the roots and stems could be used as biomonitors of Cu, the stems as biomonitors of Ni, the roots and leaves as biomonitors of Pb, and all three parts of the plant as biomonitors of Zn. According to the BCF values, in the topsoil, the "easily, freely, leachable, or exchangeable" geochemical fractions of the five metals could be more easily transferred to the roots, leaves, and stems when compared with total concentrations. Based on the TF values of Cd, Ni, and Pb, the metal transfer to the stems (or leaves) from the roots was efficient (>1.0) at most sampling sites. The results of BCF and TF showed that A. gangetica was a good phytoextractor for Cd and Ni, and a good phytostabilizer for Cu, Pb, and Zn. Therefore, A. gangetica is a good candidate as a biomonitor and a phytoremediator of Ni, Pb, and Zn for sustainable contaminant remediation subject to suitable field management strategies.
Fulltext Correction to: COVID‑19 and therapy with essential oils having antiviral, anti‑inflammatory, and immunomodulatory properties

Asif M, Saleem M, Saadullah M, Yaseen HS, Al Zarzour R

Inflammopharmacology, 2021 Apr;29(2):577.
PMID: 33609198 DOI: 10.1007/s10787-021-00788-w
Bioaccumulation of zinc in edible tropical vegetables in Peninsular Malaysia and its human health risk assessment based on various ethnicities in Malaysia

Wong KW, Yap CK, Yaacob A, Nulit R, Omar H, Aris AZ, et al.

Environ Sci Pollut Res Int, 2021 Mar 22.
PMID: 33751349 DOI: 10.1007/s11356-021-13361-3

Along with the growing utilization of zinc (Zn) and Zn-containing nanoparticles in various industries, Zn ecotoxicological evaluation on human food supply is necessary even though Zn is generally considered safe and rarely concentrated ecotoxicologically. This study aimed to investigate the bioaccumulation of Zn in 18 species of vegetables (seven leafy, nine fruity vegetables and one species each of tuber and legume) collected from two farming sites in the west coast of Peninsular Malaysia. A human health risk assessment (HHRA) was also conducted. In addition to HHRA based on the general population, HHRA based on each major ethnic group of the Malaysian society was also determined considering that the food consumption pattern would definitely be varied across ethnicities and age groups (children and adults). The study results showed that Zn concentrations were significantly higher (p < 0.05) in leafy vegetables than in other types of vegetables. However, the target hazard quotient (THQ) values were all found to be < 1.0. Therefore, based on the Malaysian ethnicities and age groups with their respective vegetable consumption patterns, the results indicated insignificant noncarcinogenic human health risk of Zn via oral consumption of vegetables by the Malaysian population. As a metric of measurement of HHRA, a comparison of THQ values could yield previously unreported insights into HHRA differences among the compared populations. A comparison of THQ values among the consumer groups indicated higher HHR for Chinese Malaysians and children due to their higher vegetable consumption and lower body weight, respectively. A comparison the Zn intakes of all the consumer groups with the recommended nutrient intakes indicated that the oral consumption of the vegetable species collected in this study would not result in Zn-related hazards and would not be able to fulfil the Zn dietary need of the individual consumer.
Fulltext RP-UHPLC-MS Chemical Profiling, Biological and In Silico Docking Studies to Unravel the Therapeutic Potential of Heliotropium crispum Desf. as a Novel Source of Neuroprotective Bioactive Compounds

Arshad A, Ahemad S, Saleem H, Saleem M, Zengin G, Abdallah HH, et al.

Biomolecules, 2021 01 04;11(1).
PMID: 33406643 DOI: 10.3390/biom11010053

Heliotropium is one of the most important plant genera to have conventional folklore importance, and hence is a potential source of bioactive compounds. Thus, the present study was designed to explore the therapeutic potential of Heliotropium crispum Desf., a relatively under-explored medicinal plant species. Methanolic extracts prepared from a whole plant of H. crispum were studied for phytochemical composition and possible in vitro and in silico biological properties. Antioxidant potential was assessed via six different assays, and enzyme inhibition potential against key clinical enzymes involved in neurodegenerative diseases (acetylcholinesterase (AChE) and butyrylcholinesterase (BChE)), diabetes (α-amylase and α-glucosidase), and skin problems (tyrosinase) was assayed. Phytochemical composition was established via determination of the total bioactive contents and reverse phase ultra-high performance liquid chromatography mass spectrometry (RP-UHPLC-MS) analysis. Chemical profiling revealed the tentative presence of 50 secondary metabolites. The plant extract exhibited significant inhibition against AChE and BChE enzymes, with values of 3.80 and 3.44 mg GALAE/g extract, respectively. Further, the extract displayed considerable free radical scavenging activity against DPPH and ABTS radicals, with potential values of 43.19 and 41.80 mg TE/g extract, respectively. In addition, the selected compounds were then docked against the tested enzymes, which have shown high inhibition affinity. To conclude, H. crispum was found to harbor bioactive compounds and showed potent biological activities which could be further explored for potential uses in nutraceutical and pharmaceutical industries, particularly as a neuroprotective agent.
Fulltext Human Health Risk Assessments of Trace Metals on the Clam Corbicula javanica in a Tropical River in Peninsular Malaysia

Yap CK, Wong KW, Al-Shami SA, Nulit R, Cheng WH, Aris AZ, et al.

Int J Environ Res Public Health, 2020 12 29;18(1).
PMID: 33383875 DOI: 10.3390/ijerph18010195

This study aimed to analyse ten trace metal concentrations in the edible part of the freshwater clam Corbicula javanica and to provide a critical assessment of the potential risks to human health through consumption of this clam as food based on well-established indices and food safety guidelines. The clams were captured from a pristine original site and transplanted to other sites with different environmental qualities. The trace metal levels in the edible total soft tissue (TST) of the clam were below those of the food safety guidelines referred to except for Pb, which exceeded the permissible limit set by the European Commission (2006) and the US Food and Drug Administration/ Center for Food Safety and Applied Nutrition); Interstate Shellfish Sanitation Conference. (USFDA/CFSAN; ISSC) (2007). The estimated daily intake (EDI) values of the clam were found to be lower than the oral reference dose and the calculated target hazard quotient (THQ) and total THQ were found to be less than 1. Therefore, in conclusion, the human health risk for consumption of TST of C. javanica at both average and high-level were insignificant regardless of the environment it was exposed to.
Fulltext COVID-19 and therapy with essential oils having antiviral, anti-inflammatory, and immunomodulatory properties

Asif M, Saleem M, Saadullah M, Yaseen HS, Al Zarzour R

Inflammopharmacology, 2020 Oct;28(5):1153-1161.
PMID: 32803479 DOI: 10.1007/s10787-020-00744-0

Coronavirus disease of 2019 (COVID-19) has emerged as a global health threat. Unfortunately, there are very limited approved drugs available with established efficacy against the SARs-CoV-2 virus and its inflammatory complications. Vaccine development is actively being researched, but it may take over a year to become available to general public. Certain medications, for example, dexamethasone, antimalarials (chloroquine/hydroxychloroquine), antiviral (remdesivir), and IL-6 receptor blocking monoclonal antibodies (tocilizumab), are used in various combinations as off-label medications to treat COVID-19. Essential oils (EOs) have long been known to have anti-inflammatory, immunomodulatory, bronchodilatory, and antiviral properties and are being proposed to have activity against SARC-CoV-2 virus. Owing to their lipophilic nature, EOs are advocated to penetrate viral membranes easily leading to membrane disruption. Moreover, EOs contain multiple active phytochemicals that can act synergistically on multiple stages of viral replication and also induce positive effects on host respiratory system including bronchodilation and mucus lysis. At present, only computer-aided docking and few in vitro studies are available which show anti-SARC-CoV-2 activities of EOs. In this review, role of EOs in the prevention and treatment of COVID-19 is discussed. A discussion on possible side effects associated with EOs as well as anti-corona virus claims made by EOs manufacturers are also highlighted. Based on the current knowledge a chemo-herbal (EOs) combination of the drugs could be a more feasible and effective approach to combat this viral pandemic.
Fulltext Prevalence of 3.7 and 4.2 deletions in Sudanese patients with red cells hypochromia and microcytosis

Osman HA, Hamid MMA, Ahmad RB, Saleem M, Abdallah SA

BMC Res Notes, 2020 Feb 10;13(1):65.
PMID: 32041645 DOI: 10.1186/s13104-020-4933-5

OBJECTIVE: Alpha-thalassemia is a genetic disorder characterized by deletions of one or more α globin genes that result in deficient of α globin chains reducing haemoglobin concentration. The study aimed to screen 97 patients with microcytosis and hypochromasia for the 3.7 and 4.2 alpha thalassemia deletion mutations.
RESULTS: Out of 97 patients screened, only 7 were carriers for the 3.7 deletion and all patients were negative for the 4.2 deletion. The 3.7 deletion was found in Foor, Hawsa and Rezagat Sudanese tribes. In the carriers of the 3.7 deletion, Red Blood Cells and Haematocrit were significantly increased. The Red Blood Cells were 7.23 ± 0.78 × 1012/L in adult males and 7.21 ± 0.67 × 1012/L in adult females while in children were 5.07 ± 0.87 × 1012/L. The mean cell volume and mean cell haemoglobin were significantly decreased, but the mean cell haemoglobin concentration slightly decreased. Haemoglobin levels didn't revealed statistically significant decrease in adult males (11.7 ± 0.57 g/dL) and adult females (11.25 ± 0.64 g/dL), while in children were (11.6 ± 2.95 g/dL). Haemoglobin electrophoresis revealed two patients of the 3.7 and 4.2 negative were carriers for β-thalassemia. The study concluded that α3.7 deletion has frequency of 0.07 in Sudanese with hypochromasia and microcytosis.
The BRCA1 and BRCA2 Genes in Early-Onset Breast Cancer Patients

Saleem M, Ghazali MB, Wahab MAMA, Yusoff NM, Mahsin H, Seng CE, et al.

Adv Exp Med Biol, 2020;1292:1-12.
PMID: 29687286 DOI: 10.1007/5584_2018_147

Approximately 5-10% of breast cancers are attributable to genetic susceptibility. Mutations in the BRCA1 and BRCA2 genes are the best known genetic factors to date. The goal of this study was to determine the structure and distribution of haplotypes of the BRCA1 and BRCA2 genes in early-onset breast cancer patients. We enrolled 70 patients diagnosed with early-onset breast cancer. A total of 21 SNPs (11 on BRCA1 and 10 on BRCA2) and 1 dinucleotide deletion on BRCA1 were genotyped using nested allele-specific PCR methods. Linkage disequilibrium (LD) analysis was conducted, and haplotypes were deduced from the genotype data. Two tightly linked LD blocks were observed on each of the BRCA1 and BRCA2 genes. Variant-free haplotypes (TAT-AG for BRCA1 and ATA-AAT for BRCA2) were observed at a frequency of more than 50% on each gene along with variable frequencies of derived haplotypes. The variant 3'-subhaplotype CGC displayed strong LD with 5'-subhaplotypes GA, AA, and GG on BRCA1 gene. Haplotypes ATA-AGT, ATC-AAT, and ATA-AAC were the variant haplotypes frequent on BRCA2 gene. Although the clinical significance of these derived haplotypes has not yet been established, it is expected that some of these haplotypes, especially the less frequent subhaplotypes, eventually will be shown to be indicative of a predisposition to early-onset breast cancer.
A novel five-step synthetic route to 1,3,4-oxadiazole derivatives with potent α-glucosidase inhibitory potential and their in silico studies

Iftikhar M, Shahnawaz, Saleem M, Riaz N, Aziz-Ur-Rehman, Ahmed I, et al.

Arch Pharm (Weinheim), 2019 Dec;352(12):e1900095.
PMID: 31544284 DOI: 10.1002/ardp.201900095

A series of new N-aryl/aralkyl derivatives of 2-methyl-2-{5-(4-chlorophenyl)-1,3,4-oxadiazole-2ylthiol}acetamide were synthesized by successive conversions of 4-chlorobenzoic acid (a) into ethyl 4-chlorobenzoate (1), 4-chlorobenzoylhydrazide (2) and 5-(4-chlorophenyl)-1,3,4-oxadiazole-2-thiol (3), respectively. The required array of compounds (6a-n) was obtained by the reaction of 1,3,4-oxadiazole (3) with various electrophiles (5a-n) in the presence of DMF (N,N-dimethylformamide) and sodium hydroxide at room temperature. The structural determination of these compounds was done by infrared, 1 H-NMR (nuclear magnetic resonance), 13 C-NMR, electron ionization mass spectrometry, and high-resolution electron ionization mass spectrometry analyses. All compounds were evaluated for their α-glucosidase inhibitory potential. Compounds 6a, 6c-e, 6g, and 6i were found to be promising inhibitors of α-glucosidase with IC50 values of 81.72 ± 1.18, 52.73 ± 1.16, 62.62 ± 1.15, 56.34 ± 1.17, 86.35 ± 1.17, 52.63 ± 1.16 µM, respectively. Molecular modeling and ADME (absorption, distribution, metabolism, excretion) predictions supported the findings. The current synthesized library of compounds was achieved by utilizing very common raw materials in such a way that the synthesized compounds may prove to be promising drug leads.
Histopathological Investigation of Skin and Hides Damage of Small and Large Ruminants due to Naturally Infested Ticks

Saleem MZ, Akhtar R, Aslam A, Rashid MI

Trop Biomed, 2019 Dec 01;36(4):1081-1086.
PMID: 33597477

Ticks are important ectoparasites which transmit many disease pathogen to animals; these are labelled tick borne diseases (TBD). Tick induced damage to skin and hides has not received attention. Skin and hides are important for the leather product industry, particularly in Pakistan. Due to economic importance and financial loss by ticks in leather industry, the present study was designed to investigate skin and hides damage due to ticks at microscopic level. Naturally tick infested tissue samples of hides and skin were collected from slaughter houses. Primary lesions at tick feeding sites showed epidermal edema with adjacent dermal edema. Histopathological examination revealed degeneration of epidermal layer down to the basal layer. Epidermal and sub dermal layers often displayed focal necrosis infiltrated with neutrophils and mononuclear cells at tick bite sites. Hyperplasia of keratinocytes was also seen at sites of ruptured epidermis. Quality of leather depends upon the grain (Outer) surface skin/hides. Ticks infestation damages the outer surface, due to bites, inflammatory responses, and secondary bacterial infections that often become established at feeding sites. Control of ticks should be given consideration to reduce infestation induced losses in the leather industry in Pakistan.
Fulltext Global, Regional, and National Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life-Years for 29 Cancer Groups, 1990 to 2017: A Systematic Analysis for the Global Burden of Disease Study

Global Burden of Disease Cancer Collaboration, Fitzmaurice C, Abate D, Abbasi N, Abbastabar H, Abd-Allah F, et al.

JAMA Oncol, 2019 Dec 01;5(12):1749-1768.
PMID: 31560378 DOI: 10.1001/jamaoncol.2019.2996

IMPORTANCE: Cancer and other noncommunicable diseases (NCDs) are now widely recognized as a threat to global development. The latest United Nations high-level meeting on NCDs reaffirmed this observation and also highlighted the slow progress in meeting the 2011 Political Declaration on the Prevention and Control of Noncommunicable Diseases and the third Sustainable Development Goal. Lack of situational analyses, priority setting, and budgeting have been identified as major obstacles in achieving these goals. All of these have in common that they require information on the local cancer epidemiology. The Global Burden of Disease (GBD) study is uniquely poised to provide these crucial data.
OBJECTIVE: To describe cancer burden for 29 cancer groups in 195 countries from 1990 through 2017 to provide data needed for cancer control planning.
EVIDENCE REVIEW: We used the GBD study estimation methods to describe cancer incidence, mortality, years lived with disability, years of life lost, and disability-adjusted life-years (DALYs). Results are presented at the national level as well as by Socio-demographic Index (SDI), a composite indicator of income, educational attainment, and total fertility rate. We also analyzed the influence of the epidemiological vs the demographic transition on cancer incidence.
FINDINGS: In 2017, there were 24.5 million incident cancer cases worldwide (16.8 million without nonmelanoma skin cancer [NMSC]) and 9.6 million cancer deaths. The majority of cancer DALYs came from years of life lost (97%), and only 3% came from years lived with disability. The odds of developing cancer were the lowest in the low SDI quintile (1 in 7) and the highest in the high SDI quintile (1 in 2) for both sexes. In 2017, the most common incident cancers in men were NMSC (4.3 million incident cases); tracheal, bronchus, and lung (TBL) cancer (1.5 million incident cases); and prostate cancer (1.3 million incident cases). The most common causes of cancer deaths and DALYs for men were TBL cancer (1.3 million deaths and 28.4 million DALYs), liver cancer (572 000 deaths and 15.2 million DALYs), and stomach cancer (542 000 deaths and 12.2 million DALYs). For women in 2017, the most common incident cancers were NMSC (3.3 million incident cases), breast cancer (1.9 million incident cases), and colorectal cancer (819 000 incident cases). The leading causes of cancer deaths and DALYs for women were breast cancer (601 000 deaths and 17.4 million DALYs), TBL cancer (596 000 deaths and 12.6 million DALYs), and colorectal cancer (414 000 deaths and 8.3 million DALYs).
CONCLUSIONS AND RELEVANCE: The national epidemiological profiles of cancer burden in the GBD study show large heterogeneities, which are a reflection of different exposures to risk factors, economic settings, lifestyles, and access to care and screening. The GBD study can be used by policy makers and other stakeholders to develop and improve national and local cancer control in order to achieve the global targets and improve equity in cancer care.
Disruption of MAPK1 expression in the ERK signalling pathway and the RUNX1‑RUNX1T1 fusion gene attenuate the differentiation and proliferation and induces the growth arrest in t(8;21) leukaemia cells

Bashanfer SAA, Saleem M, Heidenreich O, Moses EJ, Yusoff NM

Oncol Rep, 2019 Mar;41(3):2027-2040.
PMID: 30569130 DOI: 10.3892/or.2018.6926

The t(8;21) translocation is one of the most frequent chromosome abnormalities associated with acute myeloid leukaemia (AML). This abberation deregulates numerous molecular pathways including the ERK signalling pathway among others. Therefore, the aim of the present study was to investigate the gene expression patterns following siRNA‑mediated suppression of RUNX1‑RUNX1T1 and MAPK1 in Kasumi‑1 and SKNO‑1 cells and to determine the differentially expressed genes in enriched biological pathways. BeadChip microarray and gene ontology analysis revealed that RUNX1‑RUNX1T1 and MAPK1 suppression reduced the proliferation rate of the t(8;21) cells with deregulated expression of several classical positive regulator genes that are otherwise known to enhance cell proliferation. RUNX1‑RUNX1T1 suppression exerted an anti‑apoptotic effect through the overexpression of BCL2, BIRC3 and CFLAR genes, while MAPK1 suppression induced apopotosis in t(8;21) cells by the apoptotic mitochondrial changes stimulated by the activity of upregulated TP53 and TNFSF10, and downregulated JUN gene. RUNX1‑RUNX1T1 suppression supported myeloid differentiation by the differential expression of CEBPA, CEBPE, ID2, JMJD6, IKZF1, CBFB, KIT and CDK6, while MAPK1 depletion inhibited the differentiation of t(8;21) cells by elevated expression of ADA and downregulation of JUN. RUNX1‑RUNX1T1 and MAPK1 depletion induced cell cycle arrest at the G0/G1 phase. Accumulation of cells in the G1 phase was largely the result of downregulated expression of TBRG4, CCNE2, FOXO4, CDK6, ING4, IL8, MAD2L1 and CCNG2 in the case of RUNX1‑RUNX1T1 depletion and increased expression of RASSF1, FBXO6, DADD45A and P53 in the case of MAPK1 depletion. Taken together, the current results demonstrate that MAPK1 promotes myeloid cell proliferation and differentiation simultaneously by cell cycle progression while suppresing apoptosis.

Filters

Please provide feedback to Administrator (afdal@afpm.org.my)

External Links