Publications by authors named "Suliman Yousef AlOmar"

7 Publications

  • Page 1 of 1

Identification of the Key Regulators of Spina Bifida Through Graph-Theoretical Approach.

Front Genet 2021 6;12:597983. Epub 2021 Apr 6.

Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, India.

Spina Bifida (SB) is a congenital spinal cord malformation. Efforts to discern the key regulators (KRs) of the SB protein-protein interaction (PPI) network are requisite for developing its successful interventions. The architecture of the SB network, constructed from 117 manually curated genes was found to self-organize into a scale-free fractal state having a weak hierarchical organization. We identified three modules/motifs consisting of ten KRs, namely, , , , , , , , , , and . These KRs serve as the backbone of the network, they propagate signals through the different hierarchical levels of the network to conserve the network's stability while maintaining low popularity in the network. We also observed that the SB network exhibits a rich-club organization, the formation of which is attributed to our key regulators also except for and . The KRs that were found to ally with each other and emerge in the same motif, open up a new dimension of research of studying these KRs together. Owing to the multiple etiology and mechanisms of SB, a combination of several biomarkers is expected to have higher diagnostic accuracy for SB as compared to using a single biomarker. So, if all the KRs present in a single module/motif are targetted together, they can serve as biomarkers for the diagnosis of SB. Our study puts forward some novel SB-related genes that need further experimental validation to be considered as reliable future biomarkers and therapeutic targets.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fgene.2021.597983DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056047PMC
April 2021

Brain Disease Network Analysis to Elucidate the Neurological Manifestations of COVID-19.

Mol Neurobiol 2021 May 6;58(5):1875-1893. Epub 2021 Jan 6.

Amity Institute of Neuropsychology & Neurosciences, Amity University, Noida, 201303, India.

Although COVID-19 largely causes respiratory complications, it can also lead to various extrapulmonary manifestations resulting in higher mortality and these comorbidities are posing a challenge to the health care system. Reports indicate that 30-60% of patients with COVID-19 suffer from neurological symptoms. To understand the molecular basis of the neurologic comorbidity in COVID-19 patients, we have investigated the genetic association between COVID-19 and various brain disorders through a systems biology-based network approach and observed a remarkable resemblance. Our results showed 123 brain-related disorders associated with COVID-19 and form a high-density disease-disease network. The brain-disease-gene network revealed five highly clustered modules demonstrating a greater complexity of COVID-19 infection. Moreover, we have identified 35 hub proteins of the network which were largely involved in the protein catabolic process, cell cycle, RNA metabolic process, and nuclear transport. Perturbing these hub proteins by drug repurposing will improve the clinical conditions in comorbidity. In the near future, we assumed that in COVID-19 patients, many other neurological manifestations will likely surface. Thus, understanding the infection mechanisms of SARS-CoV-2 and associated comorbidity is a high priority to contain its short- and long-term effects on human health. Our network-based analysis strengthens the understanding of the molecular basis of the neurological manifestations observed in COVID-19 and also suggests drug for repurposing.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12035-020-02266-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7787249PMC
May 2021

Synergistic antimicrobial activity of N-methyl substituted pyrrolidinium-based ionic liquids and melittin against Gram-positive and Gram-negative bacteria.

Appl Microbiol Biotechnol 2020 Dec 11;104(24):10465-10479. Epub 2020 Nov 11.

Biophysical Chemistry Laboratory, Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, 110025, India.

In pharmaceutical industry, the prodrug approaches and drug-drug conjugates are being now vastly used to optimize the efficacy of the drugs for multipurpose. The combination or conjugation of antimicrobials agents with natural antimicrobials may lead to better synergistic antimicrobial activity. Currently, many publications show the potential of ionic liquids (ILs) as novel antimicrobials and even as active pharmaceutical ingredients. The current study showed the synthesis of novel pyrrolidinium-based ILs (C, x = 4, 6, 8, 10, 12) and their antibacterial activity alone and in combination with antimicrobial peptide, melittin (MEL), against clinically relevant microorganism, E. coli and S. aureus. The cytotoxicity of synthesized ILs was administered on HEK 293 cell line using MTT assay. The obtained results showed the dependency of antibacterial activity of ILs on alkyl chain length (C4 < C6 < C8 < C10 < C12). The remarkable improvement in the antibacterial efficiency of MEL was seen with ILs; however, antibacterial effect is more pronounced with IL having large alkyl chain length (C, C, and C) at their minimal concentration with MEL to disrupt the cell membrane. In addition, the binding study and haemocompatibility results showed favourable biocompatibility and stability which could potentially improve its utility for the biomedical field. KEY POINTS: • The combination of melittin and pyrrolidinium-based ILs showed improved antibacterial activity against E. coli and S. aureus which may be used for developing new antibacterial agents. • Moreover, the cytotoxicity and haemocompatibility results showed excellent biocompatibility of the combinations on human cell line and human serum albumin, respectively, which could potentially improve its utility for the biomedical field.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00253-020-10989-yDOI Listing
December 2020

Modulation of antioxidant defence system in response to berberine in Candida albicans.

Yeast 2021 02 10;38(2):157-169. Epub 2020 Dec 10.

Clinical Microbiology and Infectious Diseases, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 2193, South Africa.

Emergence of multidrug resistant species of Candida is evolving, which advocates an urgent need for the development of new therapeutic strategies and antifungal drugs. Activation of antioxidant defence system in Candida albicans is known as forefront mechanism to escape drug toxicity. This study evaluated the role of antioxidant defence genes in the susceptibility to fluconazole in C. albicans and also determined the effect of berberine on growth, antioxidant enzymes and the expression of their genes in C. albicans isolates. Expression of major antioxidant genes was significantly increased in fluconazole-resistant isolates in comparison with the susceptible group. Antifungal susceptibility against berberine showed MIC values ranging from 125 to 500 μg/ml. Berberine treatment caused upregulation of mRNA expression and enzymatic activities of the targeted major antioxidants. Interestingly, C. albicans exhibited efficient antioxidant response at lower concentrations but could not sufficiently alleviate berberine-induced oxidative stress occurring at concentrations greater than 250 μg/ml. Therefore, berberine could serve as a potent Reactive Oxygen Species (ROS)-inducing agent, disrupting the antioxidant system especially in fluconazole-resistant C. albicans to overcome antifungal drug resistance. TAKE AWAYS: Evaluated the role of antioxidant enzymes in FLC resistance in C. albicans Studied the effect of berberine on growth of different C. albicans isolates Investigated the modulation of antioxidant enzymes by berberine in C. albicans Studied the effect of berberine on antioxidant gene expression in C. albicans.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/yea.3531DOI Listing
February 2021

Distinct epigenetic regulation in patients with multidrug-resistant TB-HIV co-infection and uninfected individuals.

Mutat Res 2020 May - Dec;821:111724. Epub 2020 Oct 13.

Department of Clinical Microbiology and Infectious Diseases, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 2193, South Africa; Infectious Diseases, Charlotte Maxeke Johannesburg Academic Hospital, National Health Laboratory Service, Johannesburg, 2193, South Africa.

Background: Mycobacterium tuberculosis (Mtb) is an airborne pathogenic microorganism that causes tuberculosis (TB). This pathogen invades lung tissues causing pulmonary infections and disseminates into other host organs. The Bacillus Calmette-Guérin (BCG) vaccine is employed to provide immune protection against TB; however, its efficacy is dependent on the age, immune status and geographic location of vaccinated individuals. Advanced diagnostic approaches such as GeneXpert MTB/RIF® and line probe assays (LPAs) have allowed rapid detection of drug-resistant, multidrug-resistant (MDR) and extensively drug-resistant (XDR) Mtb strains. However, in sub-Saharan Africa, public and private health institutions are further burdened by the high prevalence of Human Immunodeficiency Virus (HIV), the causative agent of acquired immunodeficiency syndrome (AIDS) and TB co-infections across different age groups. Epigenetic mechanisms have been widely exploited by Mtb and HIV to bypass the host's innate and adaptive immune responses, leading to microbial proliferation and disease manifestation. In the current study, we investigated the impact of epigenetic mechanisms in regulating target gene expression in healthy and patients co-infected with MDR TB-HIV.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.mrfmmm.2020.111724DOI Listing
December 2020

Neutrophils Driving Unconventional T Cells Mediate Resistance against Murine Sarcomas and Selected Human Tumors.

Cell 2019 07 27;178(2):346-360.e24. Epub 2019 Jun 27.

Department of Biomedical Sciences, Humanitas University, 20090 Pieve Emanuele, Italy; Humanitas Clinical and Research Center, 20089 Rozzano, Italy. Electronic address:

Neutrophils are a component of the tumor microenvironment and have been predominantly associated with cancer progression. Using a genetic approach complemented by adoptive transfer, we found that neutrophils are essential for resistance against primary 3-methylcholantrene-induced carcinogenesis. Neutrophils were essential for the activation of an interferon-γ-dependent pathway of immune resistance, associated with polarization of a subset of CD4 CD8 unconventional αβ T cells (UTC). Bulk and single-cell RNA sequencing (scRNA-seq) analyses unveiled the innate-like features and diversity of UTC associated with neutrophil-dependent anti-sarcoma immunity. In selected human tumors, including undifferentiated pleomorphic sarcoma, CSF3R expression, a neutrophil signature and neutrophil infiltration were associated with a type 1 immune response and better clinical outcome. Thus, neutrophils driving UTC polarization and type 1 immunity are essential for resistance against murine sarcomas and selected human tumors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cell.2019.05.047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6630709PMC
July 2019

Oxygen deprivation and the cellular response to hypoxia in adipocytes - perspectives on white and brown adipose tissues in obesity.

Front Endocrinol (Lausanne) 2015 19;6:19. Epub 2015 Feb 19.

College of Science, King Saud University , Riyadh , Saudi Arabia.

Relative hypoxia has been shown to develop in white adipose tissue depots of different types of obese mouse (genetic, dietary), and this leads to substantial changes in white adipocyte function. These changes include increased production of inflammation-related adipokines (such as IL-6, leptin, Angptl4, and VEGF), an increase in glucose utilization and lactate production, and the induction of fibrosis and insulin resistance. Whether hypoxia also occurs in brown adipose tissue depots in obesity has been little considered. However, a recent study has reported low pO2 in brown fat of obese mice, this involving mitochondrial loss and dysfunction. We suggest that obesity-linked hypoxia may lead to similar alterations in brown adipocytes as in white fat cells - particularly changes in adipokine production, increased glucose uptake and lactate release, and insulin resistance. This would be expected to compromise thermogenic activity and the role of brown fat in glucose homeostasis and triglyceride clearance, underpinning the development of the metabolic syndrome. Hypoxia-induced augmentation of lactate production may also stimulate the "browning" of white fat depots through recruitment of UCP1 and the development of brite adipocytes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fendo.2015.00019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4333869PMC
March 2015