Publications by authors named "Sultan Alasmari"

11 Publications

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Radiologic technologists in Saudi Arabia: Does long-term exposure to radiation increase the risk of hematological disorders?

Saudi Med J 2021 Aug;42(8):913-917

From the Department of Clinical Laboratory Sciences (Mohammed, Sultan, Nashwa), Faculty of Applied Medical Sciences, King Khalid University, Abha; from Diagnostic Radiology Department (Nasser), College of Applied Medical Sciences, Jazan University; from the Medical Research Center (Nasser), Jazan University, Jazan; from Radiological Sciences Department (Yazeed), College of Applied Medical Sciences, King Saud University; and From Radiological Department (Hussain), Sabia General Hospital, Jazan, Kingdom of Saudi Arabia.

Objectives: To determine the influence of prolonged exposure to radiation based on dosimeter readings on hematological parameters among radiologic technologists (RTs) in Saudi Arabia.

Methods: The study was specifically conducted on selected RTs with experience of more than 10 years and the highest thermoluminescent dosimeter (TLD) readings among all RTs in the Radiological Department, Sabya General Hospital, Ministry of Health, Saudi Arabia from August to October 2020. The RTs group was compared with a control group of non-irradiated participants. Blood samples were collected for hematological and coagulation profile evaluation.

Results: The acquired radiation dose analysis revealed that the average accumulated dose in 10 years is 7.6 mSv. The medians of prothrombin time (PT) and activated partial thromboplastin time (APTT) of the RTs group were significantly lower when compared to the control group. In addition, RTs group exhibited a significant reduction in neutrophil count and an elevation in lymphocyte count.

Conclusion: Chronic exposure to radiation revealed a significant change in blood tests and may reflect an effect on RTs tissues, leading to serious health problems. However, further investigation in a large cohort to study the association between alteration in hematological parameters and chronic radiation exposure is required.
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http://dx.doi.org/10.15537/smj.2021.42.8.20210171DOI Listing
August 2021

Pioneer neutrophils release chromatin within in vivo swarms.

Elife 2021 07 21;10. Epub 2021 Jul 21.

The Bateson Centre and Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield Medical School, Sheffield, United Kingdom.

Neutrophils are rapidly recruited to inflammatory sites where their coordinated migration forms clusters, a process termed neutrophil swarming. The factors that modulate early stages of neutrophil swarming are not fully understood, requiring the development of new in vivo models. Using transgenic zebrafish larvae to study endogenous neutrophil migration in a tissue damage model, we demonstrate that neutrophil swarming is a conserved process in zebrafish immunity, sharing essential features with mammalian systems. We show that neutrophil swarms initially develop around an individual pioneer neutrophil. We observed the violent release of extracellular cytoplasmic and nuclear fragments by the pioneer and early swarming neutrophils. By combining in vitro and in vivo approaches to study essential components of neutrophil extracellular traps (NETs), we provide in-depth characterisation and high-resolution imaging of the composition and morphology of these release events. Using a photoconversion approach to track neutrophils within developing swarms, we identify that the fate of swarm-initiating pioneer neutrophils involves extracellular chromatin release and that the key NET components gasdermin, neutrophil elastase, and myeloperoxidase are required for the swarming process. Together our findings demonstrate that release of cellular components by pioneer neutrophils is an initial step in neutrophil swarming at sites of tissue injury.
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http://dx.doi.org/10.7554/eLife.68755DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8298094PMC
July 2021

Hemoglobinopathies: An update on the prevalence trends in Southern Saudi Arabia.

Saudi Med J 2021 Jul;42(7):784-789

From the Department of Clinical Laboratory Sciences (Mohammed, Sultan, Mesfer, Ayed), Faculty of Applied Medical Sciences, King Khalid University, Abha and from the Department of Microbiology (Ali), Armed Forces Hospital, Khamis Mushayt, Kingdom of Saudi Arabia.

Objectives: To investigate trends in hemoglobinopathies following the establishment of a mandatory premarital screening program (MPMSP) in the southern region of Saudi Arabia, where they are considered highly predominant.

Methods: A retrospective analysis was performed on data from 32,130 high-performance liquid chromatography (HPLC) tests between November 2017 and October 2020. The data was obtained from the Hematology section, Laboratory Department, Armed Forces Hospital, Southern Region.

Results: Despite the establishment of the MPMSP, our data showed that sickle cell disease remains a predominant hemoglobinopathy accounting for more than 7% of total tests in Southern Saudi Arabia. Observed HPLC hemoglobin fractions among the tested population showed a reduction in Hb A mean indicating a high rate of hemoglobin abnormalities. In addition, the prevalence of hemoglobin variants, including sickle cell and thalassemia, was higher in the younger population born after the MPMSP than in older subjects.

Conclusion: Even with the implementation of the MPMSP, hemoglobin abnormalities remain prevalent in southern Saudi Arabia. A longer time frame is recommended to verify the validity of the program.
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http://dx.doi.org/10.15537/smj.2021.42.7.20210273DOI Listing
July 2021

The Prevalence and Factors Associated with Musculoskeletal Pain Among Pilgrims During the Hajj.

J Pain Res 2021 9;14:369-380. Epub 2021 Feb 9.

Physiotherapy Department, College of Applied Medical Science, Taif University, Taif, Saudi Arabia.

Background: Musculoskeletal pain is a primary burden on individuals as well as social and health care systems. Annually, 2-3 million pilgrims perform the Hajj in Mecca, Saudi Arabia. The Hajj is highly physically demanding because pilgrims generally move by foot for long distances among a series of religious sites, an effort that may exceed their typical levels of physical activity. To understand the impact of musculoskeletal pain on the completion of the Hajj, it is first necessary to evaluate the extent of the problem. Accordingly, this study aimed to estimate the prevalence of musculoskeletal pain and associated factors among pilgrims during the Hajj.

Methods: A cross-sectional survey was conducted during the period of the Hajj. The participants were adult pilgrims ≥ 18 years of age. Data regarding demographics, the prevalence of falls and the point prevalence of musculoskeletal pain by anatomical site were recorded. Participants were allowed to report more than one site of pain. Prevalence, crude and adjusted risk ratios were calculated.

Results: A total of 1715 pilgrims were included in the analysis. The prevalence of falls was 13.76%. The prevalence of overall musculoskeletal pain (pain at any site) was 80.46%. Musculoskeletal pain was most commonly reported in the ankle/foot (38.34%), leg (29.89%), lower back (28.47%) and knee (21.84%). In general, musculoskeletal pain at multiple sites was more common in females and in older and obese individuals. However, there were variations in the importance of sex, age and body mass index as associated factors across different pain sites.

Conclusion: Musculoskeletal pain is common among pilgrims. Unlike most populations examined in other studies, ankle/foot pain was the most common in pilgrims. These data provide guidance for potential preventative programs and the allocation of resources to optimize pilgrims' experiences and ability to complete the Hajj.
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http://dx.doi.org/10.2147/JPR.S293338DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7881773PMC
February 2021

Synergistic efficacies of thymoquinone and standard antibiotics against multi-drug resistant isolates.

Saudi Med J 2021 Feb;42(2):196-204

From the Department of Clinical Laboratory Sciences, Central Research Laboratory (Dera, Ahmad, Rajagopalan, Al Shahrani, Alshahrani, Alraey, Alamri, Alasmari, Makkawi, Alkhathami, Zaman, Hakami, Alhefzi), College of Applied Medical Sciences, King Khalid University, and From the Department of Clinical Laboratory Sciences, Central Research Laboratory (AlAmri), College of Applied Medical Sciences, and Cancer Research Unit, King Khalid University, Abha; from the Department of Clinical Laboratory Sciences (Saif), College of Applied Medical Sciences, Najran University, Najran; and the Chair of Medical and Molecular Genetics Research, Department of Clinical Laboratory Sciences (Alfhili), College of Applied Medical Sciences, King Saud University, Riyadh, Kingdom of Saudi Arabia.

Objectives: To explore the antibacterial activity of thymoquinone (TQ), a quinone extracted from .

Methods: This study was conducted from May 2019 to March 2020 at the Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha, Saudi Arabia. The antimicrobial activity, minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC) of TQ were determined using an agar well diffusion method and broth microdilution assays, and the synergistic effect was evaluated using antibiotics in parallel. The disruptive effect of TQ on bacterial cell membranes was determined using scanning electron microscopy. The antivirulence properties of TQ, which include adherence and biofilm formation, were also investigated using adherence and biofilm formation assays, respectively.

Results: Thymoquinone demonstrated bactericidal efficacy against 4/14 bacterial strains, with MIC range of 1.04-8.3 µg/mL and and MBC range of 10.41-66.66 µg/mL. Thymoquinone showed synergism against , (American Type Culture Collection 12228), , and in combination with the tested antibiotics. Thymoquinone inhibited bacterial adhesion by 39%-54%, 48%-68%, and 61%-81% at 0.5 × MIC, 1 × MIC, and 2 × MIC, respectively. The tested bacterial strains significantly inhibited biofilm formation after treatment with various concentrations of TQ for 24 and 48 hours.

Conclusion: The combinatory effect of TQ with antimicrobials should be considered when developing new antimicrobial therapy regimens to overcome multidrug-resistant.
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http://dx.doi.org/10.15537/smj.2021.2.25706DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7989283PMC
February 2021

Body Mass Index and Its Association with Genetically Transmitted Traits.

Biomed Res Int 2020 21;2020:3469316. Epub 2020 Dec 21.

Department of Clinical Laboratory Sciences, Faculty of Applied Medical Sciences, King Khalid University, Guraiger, Abha 62529, Saudi Arabia.

Background: Body mass index (BMI) is a metric widely used to measure the healthy weight of an individual and to predict a person's risk of developing serious illnesses. Study the statistical association between genetically transmitted traits and BMI might be of interest.

Objectives: The present study designed to extend the inadequate evidence concerning the influence of some genetically transmitted traits including ABO blood type, Rh factor, eye color, and hair color on BMI variation.

Methods: A total of 142 undergraduate female students of the Department of Clinical Laboratory Sciences, Faculty of Applied Medical Sciences, King Khalid University, Abha, Saudi Arabia, were participated to investigate the possible linkage between genetic traits and BMI variations. Height and weight are collected from participants for BMI measurement. ABO blood type and Rh factor were determined by antisera.

Results: Out of 142 female students, 48 were categorized in the first tertile (T1: less than 19.8 kg/m), 50 were categorized in the second tertile (T2: between 19.8 and 23.7 kg/m), and 44 were categorized in the third tertile (T3: greater than 23.7 kg/m). Chi-square analysis shows that there were no associations of genetic traits including hair color, eye color, ABO blood type, and Rh blood type with BMI. However, a significant association between hair color and BMI was observed using multinomial logistic regression analysis.

Conclusions: Our data provides a more robust prediction of the relative influence of genetic effects such as hair color on BMI. Future studies may contribute to identifying more association between genes involved in hair pigmentation and BMI variation.
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http://dx.doi.org/10.1155/2020/3469316DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7769646PMC
September 2021

Computational and in vitro characterization of ICY-5: A potential candidate promoting mitochondrial apoptosis via the c-MET and STAT3 pathways.

J Cell Physiol 2021 01 2;236(1):146-156. Epub 2020 Jun 2.

Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha, Saudi Arabia.

Targeted chemotherapy remains the primary choice in controlling various forms of breast cancer (BC) due to its heterogenous gene expressions in various subtypes. In silico and in vitro evaluation of ICY-5, a novel arylidene analogue against c-MET, was performed. ICY-5 exhibited a docking score of -9.6 kcal/mol in inactive conformation and, - 8.6 kcal/mol in active conformation for c-MET. ICY-5 inhibited c-MET enzyme with an IC of 34.34 nM. The compound effectively inhibited MDA-MB 231 and MCF-7 cell proliferation, with GI values of 62.61 and 75.31 nM, respectively, and hepatocyte growth factor (HGF)/R c-MET phosphorylation with IC s of 71.41 and 83.77 nM, respectively. ICY-5 dose-dependently inhibited HGF-induced transmigration, cell scattering, invasion and altered cell cycle. An increase in apoptotic populations of these cells, with a dose-dependent decease in phosphorylation of STAT3 protein was observed. Furthermore, ICY-5 upregulated the caspase-3, caspase-9, Bcl-2-associated X and survivin, and downregulated Bcl-2, vascular endothelial growth factor, matrix metalloproteinase-2 (MMP-2), and MMP-9 in both BC cell lines. In summary, ICY-5 exhibited excellent efficacy in BC cells, targeting c-MET/SAT-3-mediated mitochondrial apoptosis. Further research will be required to ascertain ICY-5 suitability as a targeted chemotherapeutic against multiple forms of BC.
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http://dx.doi.org/10.1002/jcp.29830DOI Listing
January 2021

Imaging of Neutrophil Extracellular Traps (NETs): Visualization Methods and Outcomes.

Biomed Res Int 2020 1;2020:4192745. Epub 2020 Feb 1.

Clinical Laboratory Sciences, Faculty of Applied Medical Sciences, King Khalid University, Abha 62529, Asir Region, Saudi Arabia.

Neutrophils comprise the first line of innate immune defense during a host-pathogen interaction. They attack microorganisms directly through three different methods, of which, phagocytosis and degranulation have been known and well-studied for decades. The formation of neutrophil extracellular traps (NETs) is the third and unique method, which was unveiled in 2004. Since then, many studies on NETs have been carried out. However, only few have successfully demonstrated the activity of NETs . Results of the studies on NETs have strengthened our understanding of their role in different situations. This review highlights the main studies, which have contributed in extending our understanding of the role of NETs during infections and diseases, thus indicating their advantages and limitations.
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http://dx.doi.org/10.1155/2020/4192745DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7015184PMC
November 2020

Macrophages protect Talaromyces marneffei conidia from myeloperoxidase-dependent neutrophil fungicidal activity during infection establishment in vivo.

PLoS Pathog 2018 06 8;14(6):e1007063. Epub 2018 Jun 8.

Australian Regenerative Medicine Institute, Monash University, Clayton, Victoria, Australia.

Neutrophils and macrophages provide the first line of cellular defence against pathogens once physical barriers are breached, but can play very different roles for each specific pathogen. This is particularly so for fungal pathogens, which can occupy several niches in the host. We developed an infection model of talaromycosis in zebrafish embryos with the thermally-dimorphic intracellular fungal pathogen Talaromyces marneffei and used it to define different roles of neutrophils and macrophages in infection establishment. This system models opportunistic human infection prevalent in HIV-infected patients, as zebrafish embryos have intact innate immunity but, like HIV-infected talaromycosis patients, lack a functional adaptive immune system. Importantly, this new talaromycosis model permits thermal shifts not possible in mammalian models, which we show does not significantly impact on leukocyte migration, phagocytosis and function in an established Aspergillus fumigatus model. Furthermore, the optical transparency of zebrafish embryos facilitates imaging of leukocyte/pathogen interactions in vivo. Following parenteral inoculation, T. marneffei conidia were phagocytosed by both neutrophils and macrophages. Within these different leukocytes, intracellular fungal form varied, indicating that triggers in the intracellular milieu can override thermal morphological determinants. As in human talaromycosis, conidia were predominantly phagocytosed by macrophages rather than neutrophils. Macrophages provided an intracellular niche that supported yeast morphology. Despite their minor role in T. marneffei conidial phagocytosis, neutrophil numbers increased during infection from a protective CSF3-dependent granulopoietic response. By perturbing the relative abundance of neutrophils and macrophages during conidial inoculation, we demonstrate that the macrophage intracellular niche favours infection establishment by protecting conidia from a myeloperoxidase-dependent neutrophil fungicidal activity. These studies provide a new in vivo model of talaromycosis with several advantages over previous models. Our findings demonstrate that limiting T. marneffei's opportunity for macrophage parasitism and thereby enhancing this pathogen's exposure to effective neutrophil fungicidal mechanisms may represent a novel host-directed therapeutic opportunity.
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http://dx.doi.org/10.1371/journal.ppat.1007063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6010348PMC
June 2018

Intron retention enhances gene regulatory complexity in vertebrates.

Genome Biol 2017 11 16;18(1):216. Epub 2017 Nov 16.

Gene & Stem Cell Therapy Program, Centenary Institute, University of Sydney, Camperdown, 2050, NSW, Australia.

Background: While intron retention (IR) is now widely accepted as an important mechanism of mammalian gene expression control, it remains the least studied form of alternative splicing. To delineate conserved features of IR, we performed an exhaustive phylogenetic analysis in a highly purified and functionally defined cell type comprising neutrophilic granulocytes from five vertebrate species spanning 430 million years of evolution.

Results: Our RNA-sequencing-based analysis suggests that IR increases gene regulatory complexity, which is indicated by a strong anti-correlation between the number of genes affected by IR and the number of protein-coding genes in the genome of individual species. Our results confirm that IR affects many orthologous or functionally related genes in granulocytes. Further analysis uncovers new and unanticipated conserved characteristics of intron-retaining transcripts. We find that intron-retaining genes are transcriptionally co-regulated from bidirectional promoters. Intron-retaining genes have significantly longer 3' UTR sequences, with a corresponding increase in microRNA binding sites, some of which include highly conserved sequence motifs. This suggests that intron-retaining genes are highly regulated post-transcriptionally.

Conclusions: Our study provides unique insights concerning the role of IR as a robust and evolutionarily conserved mechanism of gene expression regulation. Our findings enhance our understanding of gene regulatory complexity by adding another contributor to evolutionary adaptation.
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http://dx.doi.org/10.1186/s13059-017-1339-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5688624PMC
November 2017

A zebrafish model of inflammatory lymphangiogenesis.

Biol Open 2015 Sep 14;4(10):1270-80. Epub 2015 Sep 14.

Department of Molecular Medicine & Pathology, School of Medical Sciences, University of Auckland, Auckland 1142, New Zealand

Inflammatory bowel disease (IBD) is a disabling chronic inflammatory disease of the gastrointestinal tract. IBD patients have increased intestinal lymphatic vessel density and recent studies have shown that this may contribute to the resolution of IBD. However, the molecular mechanisms involved in IBD-associated lymphangiogenesis are still unclear. In this study, we established a novel inflammatory lymphangiogenesis model in zebrafish larvae involving colitogenic challenge stimulated by exposure to 2,4,6-trinitrobenzenesulfonic acid (TNBS) or dextran sodium sulphate (DSS). Treatment with either TNBS or DSS resulted in vascular endothelial growth factor receptor (Vegfr)-dependent lymphangiogenesis in the zebrafish intestine. Reduction of intestinal inflammation by the administration of the IBD therapeutic, 5-aminosalicylic acid, reduced intestinal lymphatic expansion. Zebrafish macrophages express vascular growth factors vegfaa, vegfc and vegfd and chemical ablation of these cells inhibits intestinal lymphatic expansion, suggesting that the recruitment of macrophages to the intestine upon colitogenic challenge is required for intestinal inflammatory lymphangiogenesis. Importantly, this study highlights the potential of zebrafish as an inflammatory lymphangiogenesis model that can be used to investigate the role and mechanism of lymphangiogenesis in inflammatory diseases such as IBD.
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http://dx.doi.org/10.1242/bio.013540DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4610225PMC
September 2015
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