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Abdul Haseeb

Bio: Abdul Haseeb is an academic researcher from Children's Hospital of Philadelphia. The author has contributed to research in topics: Mathematics & Pure mathematics. The author has an hindex of 17, co-authored 38 publications receiving 1208 citations. Previous affiliations of Abdul Haseeb include Northeast Ohio Medical University & University of Kansas.


Papers
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Journal ArticleDOI
TL;DR: There is considerable success in the treatment of rheumatoid arthritis using anti-cytokine therapies in OA, however, these therapies did not show much effect, highlighting more complex nature of pathogenesis of OA.

312 citations

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TL;DR: The data indicates that Wogonin exerts chondroprotective effects through the suppression of molecular events involved in oxidative stress, inflammation and matrix degradation in OA chONDrocytes and cartilage explants.

198 citations

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TL;DR: The effects of SFAs on the aforementioned genes except PPARgamma could be extrapolated towards decreased insulin sensitivity, while only the alteration in the mRNA levels of PPargamma and resistin could be associated with insulin resistance in TFA-fed rats.
Abstract: Objective: Trans-fatty acids (TFAs) are formed during partial hydrogenation of vegetable oils and are shown to be more atherogenic than saturated fatty acids (SFAs). Our previous study showed that dietary TFAs decrease adipose tissue insulin sensitivity to a greater extent than SFAs in rats. We hypothesized that the effects of these fatty acids on insulin sensitivity could be mediated through an alteration in gene expression. In the current study we have investigated the effects of dietary TFAs or SFAs on expression of genes associated with insulin sensitivity in rat adipose tissue. Design and methods: Male weanling Wistar/NIN rats were divided into four groups and fed one of the following diets containing 10% fat (g/100g diet) differing only in the fatty acid composition for 3 months: control diet (3.7% linoleic acid (LA)), SFA diet (5% SFA), TFA diet 1 (1.5% TFA þ 1% LA) and TFA diet 2 (1.5% TFA þ 2% LA). The mRNA expression of peroxisome proliferator-activated receptor g (PPARg), lipoprotein lipase (LPL), glucose transporter-4 (GLUT4), resistin and adiponectin was analyzed in epididymal fat using RT-PCR. The effects of TFA were studied at two levels of LA to understand the beneficial effects of LA over the effects of TFA. Results: Both dietary SFA and TFA upregulated the mRNA levels of resistin. Dietary SFA downregulated adiponectin and GLUT4 and upregulated LPL, while TFA downregulated PPARg and LPL. The effects of dietary TFA on PPARg and resistin were not counteracted by increased LA (TFA diet 2). Conclusion: The effects of SFAs on the aforementioned genes except PPARg could be extrapolated towards decreased insulin sensitivity, while only the alteration in the mRNA levels of PPARg and resistin could be associated with insulin resistance in TFA-fed rats. These findings suggest that dietary SFAs and TFAs alter the expression of different genes associated with insulin sensitivity in adipose tissue.

132 citations

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TL;DR: Current knowledge, recent discoveries, and propose new research directions to answer remaining questions about SOX9 activities and regulation are reviewed.

118 citations

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TL;DR: Results indicate that elevated expression of alpha-crystallins in some tissues may have implications in pathophysiology of diabetic complications and increased oxidative stress appears to be a major stimulus for the enhanced expression ofalphaA- and alphaB- Crystallin in the tissues of diabetic rats.

97 citations


Cited by
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Journal ArticleDOI
TL;DR: The authors consider the feasibility and potential implications of reducing or eliminating the consumption of trans fatty acids from partially hydrogenated vegetable oils in the United States.
Abstract: The intake of trans fat has been associated with coronary heart disease, sudden death from cardiac causes, and diabetes. This article reviews the evidence for physiological and cellular effects of trans fatty acids, unsaturated fatty acids with at least one double bond in the trans configuration. The authors consider the feasibility and potential implications of reducing or eliminating the consumption of trans fatty acids from partially hydrogenated vegetable oils in the United States.

1,582 citations

Journal ArticleDOI
TL;DR: Evidence for the potential role of curcumin in the prevention and treatment of various proinflammatory chronic diseases is provided and its features, combined with the pharmacological safety and negligible cost, renderCurcumin an attractive agent to explore further.

1,542 citations

Journal ArticleDOI
TL;DR: Molecular mechanisms underlying the roles of T NF in homeostasis and inflammatory disease pathogenesis are presented, and novel strategies to advance therapeutic paradigms for the treatment of TNF-mediated diseases are discussed.
Abstract: TNF is a pleiotropic cytokine with important functions in homeostasis and disease pathogenesis. Recent discoveries have provided insights into TNF biology that introduce new concepts for the development of therapeutics for TNF-mediated diseases. The model of TNF receptor signalling has been extended to include linear ubiquitination and the formation of distinct signalling complexes that are linked with different functional outcomes, such as inflammation, apoptosis and necroptosis. Our understanding of TNF-induced gene expression has been enriched by the discovery of epigenetic mechanisms and concepts related to cellular priming, tolerization and induction of 'short-term transcriptional memory'. Identification of distinct homeostatic or pathogenic TNF-induced signalling pathways has introduced the concept of selectively inhibiting the deleterious effects of TNF while preserving its homeostatic bioactivities for therapeutic purposes. In this Review, we present molecular mechanisms underlying the roles of TNF in homeostasis and inflammatory disease pathogenesis, and discuss novel strategies to advance therapeutic paradigms for the treatment of TNF-mediated diseases.

856 citations

Journal ArticleDOI
TL;DR: Osteoarthritis has long been viewed as a degenerative disease of cartilage, but accumulating evidence indicates that inflammation has a critical role in its pathogenesis, and increasing insight into the inflammatory underpinnings of OA holds promise for the development of new, disease-modifying therapies.
Abstract: Osteoarthritis (OA) has long been viewed as a degenerative disease of cartilage, but accumulating evidence indicates that inflammation has a critical role in its pathogenesis. Furthermore, we now appreciate that OA pathogenesis involves not only breakdown of cartilage, but also remodelling of the underlying bone, formation of ectopic bone, hypertrophy of the joint capsule, and inflammation of the synovial lining. That is, OA is a disorder of the joint as a whole, with inflammation driving many pathologic changes. The inflammation in OA is distinct from that in rheumatoid arthritis and other autoimmune diseases: it is chronic, comparatively low-grade, and mediated primarily by the innate immune system. Current treatments for OA only control the symptoms, and none has been FDA-approved for the prevention or slowing of disease progression. However, increasing insight into the inflammatory underpinnings of OA holds promise for the development of new, disease-modifying therapies. Indeed, several anti-inflammatory therapies have shown promise in animal models of OA. Further work is needed to identify effective inhibitors of the low-grade inflammation in OA, and to determine whether therapies that target this inflammation can prevent or slow the development and progression of the disease.

815 citations

Journal ArticleDOI
TL;DR: An overview of the physiological and pathological roles of NRF2 is provided, emerging pharmacological modulators of theNRF2–KEAP1 axis are presented and associated drug development challenges are highlighted.
Abstract: The transcription factor NF-E2 p45-related factor 2 (NRF2; encoded by NFE2L2) and its principal negative regulator, the E3 ligase adaptor Kelch-like ECH-associated protein 1 (KEAP1), are critical in the maintenance of redox, metabolic and protein homeostasis, as well as the regulation of inflammation. Thus, NRF2 activation provides cytoprotection against numerous pathologies including chronic diseases of the lung and liver; autoimmune, neurodegenerative and metabolic disorders; and cancer initiation. One NRF2 activator has received clinical approval and several electrophilic modifiers of the cysteine-based sensor KEAP1 and inhibitors of its interaction with NRF2 are now in clinical development. However, challenges regarding target specificity, pharmacodynamic properties, efficacy and safety remain.

712 citations