5 results on '"Usmani D"'
Search Results
2. Cell-specific Systemic Immune Signatures Associated with Treatment Burden in Neovascular Age-related Macular Degeneration.
- Author
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Lin JB, Santeford A, Usmani D, Shah AV, Ruzycki PA, and Apte RS
- Abstract
Purpose: Choroidal neovascularization (CNV) accounts for the majority of severe vision loss in neovascular age-related macular degeneration (AMD). Despite therapies that target VEGF, patients are often under-responsive, require frequent eye injections to control disease, and eventually lose some vision despite chronic therapy implicating a multifactorial etiology in treatment response. Genetic studies implicate systemic immunity in AMD and systemic immune cells accumulate within CNV lesions, yet a role for these cells in anti-VEGF response remains undetermined. The purpose of this study was to identify transcriptional signatures of circulating immune cells that are associated with high anti-VEGF treatment burden., Design: Experimental pilot study., Participants: Patients with neovascular AMD seen at Washington University School of Medicine in St. Louis and BJC Health System., Methods: We profiled by single cell RNA sequencing the peripheral blood mononuclear cells of 27 treatment-experienced patients with wet AMD. We stratified this cohort into 2 groups with low and high treatment burden (≤ 5 or ≥ 6 injections in the past 12 months, respectively)., Main Outcome Measures: Identification of immune cells associated with high treatment burden., Results: Gene expression signature of CD16+ monocytes may be associated with high treatment burden., Conclusions: These studies delineate potential signatures of circulating immune cells that may be associated with high treatment burden in neovascular AMD, potentially informing the development of diagnostic predictors of anti-VEGF response and new precision medicine-based approaches to complement anti-VEGF therapies., Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (© 2023 by the American Academy of Ophthalmology.)
- Published
- 2023
- Full Text
- View/download PDF
3. Loss of stearoyl-CoA desaturase 2 disrupts inflammatory response in macrophages.
- Author
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Lin JB, Mora A, Wang TJ, Santeford A, Usmani D, Ligon MM, Mysorekar IU, and Apte RS
- Subjects
- Animals, Mice, Base Sequence, Fatty Acids metabolism, Inflammation genetics, Macrophages metabolism, Lipopolysaccharides, Stearoyl-CoA Desaturase genetics, Stearoyl-CoA Desaturase metabolism
- Abstract
Macrophages are innate immune cells that patrol tissues and are the first responders to detect infection. They orchestrate the host immune response in eliminating invading pathogens and the subsequent transition from inflammation to tissue repair. Macrophage dysfunction contributes to age-related pathologies, including low-grade inflammation in advanced age that is termed "inflammaging." Our laboratory has previously identified that macrophage expression of a fatty acid desaturase, stearoyl-CoA desaturase 2 (SCD2), declines with age. Herein, we delineate the precise cellular effects of SCD2 deficiency in murine macrophages. We found that deletion of Scd2 from macrophages dysregulated basal and bacterial lipopolysaccharide (LPS)-stimulated transcription of numerous inflammation-associated genes. Specifically, deletion of Scd2 from macrophages decreased basal and LPS-induced expression of Il1b transcript that corresponded to decreased production of precursor IL1B protein and release of mature IL1B. Furthermore, we identified disruptions in autophagy and depletion of unsaturated cardiolipins in SCD2-deficient macrophages. To assess the functional relevance of SCD2 in the macrophage response to infection, we challenged SCD2-deficient macrophages with uropathogenic Escherichia coli and found that there was impaired clearance of intracellular bacteria. This increased burden of intracellular bacteria was accompanied by increased release of pro-inflammatory cytokines IL6 and TNF but decreased IL1B. Taken together, these results indicate that macrophage expression of Scd2 is necessary for maintaining the macrophage response to inflammatory stimuli. This link between fatty acid metabolism and fundamental macrophage effector functions may potentially be relevant to diverse age-related pathologies. IMPORTANCE Macrophages are immune cells that respond to infection, but their dysfunction is implicated in many age-related diseases. Recent evidence showed that macrophage expression of a fatty acid enzyme, stearoyl-CoA desaturase 2, declines in aged organisms. In this work, we characterize the effects when stearoyl-CoA desaturase 2 is deficient in macrophages. We identify aspects of the macrophage inflammatory response to infection that may be affected when expression of a key fatty acid enzyme is decreased, and these findings may provide cellular insight into how macrophages contribute to age-related diseases., Competing Interests: The authors declare no conflict of interest.
- Published
- 2023
- Full Text
- View/download PDF
4. THE ROLE OF EXERCISE IN PREVENTING CHRONIC DISEASES: CURRENT EVIDENCE AND RECOMMENDATIONS.
- Author
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Usmani D, Ganapathy K, Patel D, Saini A, Gupta J, and Dixit S
- Subjects
- Humans, Chronic Disease, Blood Pressure, Risk Factors, Exercise, Hypertension prevention & control
- Abstract
Regular exercise helps to enhance health outcomes and lower risk factors, making it a crucial element in the prevention of chronic diseases. By being physically active, people can improve their general health and delay the onset of a number of chronic illnesses. For understanding the relationship between increased physical activity or decreased physical inactivity and favorable health outcomes, observational studies are the main source of information. We will look for systematic analyses of randomized controlled trials with a main emphasis on outcomes linked to diseases in the Cochrane Database of systematic studies. Evaluation will be limited to those in a few key chronic conditions. Preventing chronic illness and achieving better results in the management or treatment of chronic illness are the main outcomes of interest. For each chronic condition (such as the control of glucose in diabetes or any change in hypertension blood pressure), these results will be summarized and displayed. The design and implementation of chronic conditions, physical exercise illness conditions, and adverse physical activity-related events are of secondary interest. Our findings should help decision-makers, guideline organizations, and academics identify the most effective physical activity programs for major chronic disease management and prevention. Exercise and physical activity (PA) offers a non-invasive approach to the management of chronic disorders. More physiological, biochemical, and molecular data on the positive effects of PA and exercise on health should constitute a primary focus of future studies.
- Published
- 2023
5. The Role of Natural Products and Their Multitargeted Approach to Treat Solid Cancer.
- Author
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Muhammad N, Usmani D, Tarique M, Naz H, Ashraf M, Raliya R, Tabrez S, Zughaibi TA, Alsaieedi A, Hakeem IJ, and Suhail M
- Subjects
- Humans, Immunotherapy, Neovascularization, Pathologic drug therapy, Phytochemicals therapeutic use, Biological Products pharmacology, Biological Products therapeutic use, Neoplasms drug therapy
- Abstract
Natural products play a critical role in the discovery and development of numerous drugs for the treatment of various types of cancer. These phytochemicals have demonstrated anti-carcinogenic properties by interfering with the initiation, development, and progression of cancer through altering various mechanisms such as cellular proliferation, differentiation, apoptosis, angiogenesis, and metastasis. Treating multifactorial diseases, such as cancer with agents targeting a single target, might lead to limited success and, in many cases, unsatisfactory outcomes. Various epidemiological studies have shown that the steady consumption of fruits and vegetables is intensely associated with a reduced risk of cancer. Since ancient period, plants, herbs, and other natural products have been used as healing agents. Likewise, most of the medicinal ingredients accessible today are originated from the natural resources. Regardless of achievements, developing bioactive compounds and drugs from natural products has remained challenging, in part because of the problem associated with large-scale sequestration and mechanistic understanding. With significant progress in the landscape of cancer therapy and the rising use of cutting-edge technologies, we may have come to a crossroads to review approaches to identify the potential natural products and investigate their therapeutic efficacy. In the present review, we summarize the recent developments in natural products-based cancer research and its application in generating novel systemic strategies with a focus on underlying molecular mechanisms in solid cancer.
- Published
- 2022
- Full Text
- View/download PDF
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