Publications by authors named "Saeed Awad M Alqahtani"

3 Publications

  • Page 1 of 1

Leflunomide Induces Dose-Dependent Lung Injury in Mice via Stimulating Vimentin and NLRP3 Inflammasome Production.

Front Pharmacol 2021 23;12:631216. Epub 2021 Apr 23.

Department of Clinical Pharmacology, Faculty of Medicine, Mansoura University, Mansoura, Egypt.

Recently, the therapeutic importance of the anti-rheumatic drug, leflunomide, has been increased after the involvement of leflunomide in treating other autoimmune diseases and its promising role in retarding human malignancies. Few studies have focused on the safety in human or animals without clear outlining of the pathologic features on target organs. One clinical study related leflunomide with significant pulmonary complications in predisposed individuals. The current study examined the dose-dependent lung injury produced by leflunomide in healthy mice. Albino mice were allocated into four different groups. Group (1): Vehicle control group, Group (2-4): mice received leflunomide (2.5, 5 or 10 mg/kg), respectively, for 8 weeks and then lungs were dissected from the mice for histopathological examination and fibrosis evaluation (Masson's trichrome staining and α-smooth muscle actin immunohistochemistry). Enzyme linked immunosorbent assay was used to assess the vimentin and other inflammatory factors in the lung homogenate whereas Western blot analysis was employed to assess α-smooth muscle actin, vimentin and collagen 1. Results indicated that leflunomide induced dose-dependent pulmonary injury and the high dose and increased the vimentin, inflammatory markers (NLRP3 and interlukin-1β). Histologic examination showed distorted architecture, marked inflammatory cells infiltrate and increase collagen content. The findings were supported by Western blotting and the immunohistochemical study which showed greater pulmonary α-smooth muscle actin and vimentin content. In conclusion, the current results highlighted that leflunomide produced dose-dependent pulmonary toxicities that requires further investigation of the nature of injury.
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http://dx.doi.org/10.3389/fphar.2021.631216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8115235PMC
April 2021

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