Research Papers by Sheikh Umar Ahmad
Frontiers in Oncology, 2021
Ultraviolet (UV) exposure to the skin causes photo-damage and acts as the primary etiological age... more Ultraviolet (UV) exposure to the skin causes photo-damage and acts as the primary etiological agent in photo-carcinogenesis. UV-B exposure induces cellular damage and is the major factor challenging skin homeostasis. Autophagy allows the fundamental adaptation of cells to metabolic and oxidative stress. Cellular dysfunction has been observed in aged tissues and in toxic insults to cells undergoing stress. Conversely, promising anti-aging strategies aimed at inhibiting the mTOR pathway have been found to significantly improve the aging-related disorders. Recently, autophagy has been found to positively regulate skin homeostasis by enhancing DNA damage recognition. Here, we investigated the geno-protective roles of autophagy in UV-B-exposed primary human dermal fibroblasts (HDFs). We found that UV-B irradiation to HDFs impairs the autophagy response in a time-and intensity-independent manner. However, improving autophagy levels in HDFs with pharmacological activators regulates the UV-B-induced cellular stress by decreasing the induction of DNA photoadducts, promoting the DNA repair process, alleviating oxidative and ER stress responses, and regulating the expression levels of key cell cycle regulatory proteins. Autophagy also prevents HDFs from UV-B-induced nuclear damage as is evident in TUNEL assay and Acridine Orange/Ethidium Bromide co-staining. Salubrinal (an eIF 2 a phosphatase inhibitor) relieves ER stress response in cells and also significantly alleviates DNA damage and promotes the repair process in UV-B-exposed HDFs. P62-silenced HDFs show enhanced DNA damage response and also disturb the tumor suppressor PTEN/pAKT signaling axis in UV-B-exposed HDFs whereas Atg7-silenced HDFs reveal an unexpected consequence by decreasing the UV-B-induced DNA damage. Taken together, these results suggest that interventional autophagy offers significant protection against UV-B radiation-induced photodamage and holds great promise in devising it as a suitable therapeutic strategy against skin pathological disorders.
Vandana Publications, 2020
Every year there's a marked increase in the number of cancer patients registered in the valley's ... more Every year there's a marked increase in the number of cancer patients registered in the valley's premiere tertiary care institute, SKIMS, where increasing number of cancer patients, especially from the poor backgrounds, continue to pour in for treatment. Sounding alarm bells, leading oncologists caution that cancer has become the number one killer disease in Kashmir and that there's a need for more, and better, cancer awareness, and latest treatment facilities to ease the suffering of rising cancer patients in the valley. In this brief comment, going beyond the statistics, I put the spotlight on various aspects and reasons of cancer rise in the valley.
BioRxiv, 2020
Ultraviolet-B (UV-B) exposure to the skin causes photo-damage and acts as the primary etiological... more Ultraviolet-B (UV-B) exposure to the skin causes photo-damage and acts as the primary etiological agent in photo-carcinogenesis. UV-B exposure induces photodamage in epidermal cells and is the major factor that challenges skin homeostasis. Autophagy allows fundamental adaptation of cells to metabolic needs and stresses. Cellular dysfunction is observed in aged tissues and in toxic insults to cells that undergo stress. Conversely, promising anti-ageing strategies aimed at inhibiting the mTOR pathway has been found to significantly improve the ageing-related disorders. Recently, autophagy has been found to positively regulate skin homeostasis by enhancing DNA damage recognition. Here we investigated the Geno-protective roles of autophagy in UV-B exposed primary HDFs. We found that improving autophagy levels in HDFs regulates UV-B mediated cellular stress by decreasing the formation of DNA photo adducts, alleviates oxidative and ER stress response and by regulating the expression levels of cell cycle regulatory proteins P21 and P27. Autophagy also prevents HDFs from UV-B -induced nuclear damage as is evident from Tunnel assay and Acridine Orange/Ethidium Bromide co-staining. Salubrinal, (an eIf2α inhibitor) significantly decreases the DNA damage response in HDFs. P62 silenced HDFs show enhanced DNA damage response and disturbs the tumour suppressor axis PTEN/pAKT towards damage whereas ATG7 silenced HDFs reveal an unexpected consequence by decreasing the UV-B -induced DNA damage compared to UV-B treated HDFs. Together, our results suggest that autophagy is essential in protecting skin cells from UV-B radiation-induced photo-damage and holds great promise in devising it as a suitable therapeutic strategy against skin photo-damage.
International Journal for Research in Applied Sciences and Biotechnology, 2020
COVID-19 pandemic has put the whole world in cauldron as almost each and every nation is affected... more COVID-19 pandemic has put the whole world in cauldron as almost each and every nation is affected by this deadly virus. Intense research is going on world over to demystify the microscopic involvements of this virus, how and whom it infects and in devising out a suitable treatment strategy in containing this pandemic. Till now there is no suitable therapeutic strategy available yet and people are advised to maintain social distancing protocols to protect themselves from contracting this disease. If we talk of symptoms, there are new things coming to fore what was initially thought out with new classes of symptoms continuously added to the already existing list and presumed to be directly aggravated on contracting COVID infection. Among various other factors that greatly increase the chances of getting infected and in aggravating the symptoms in COVID-19, poor lung health among elderly population has been found to significantly increase the chances of contracting the viral disease, exacerbating the disease condition & in poor prognosis to available treatment strategies. Hookah smoking is very common among majority of elderly population in Kashmir & cigarette smoking in younger lots could turn out devastating if the world pandemic takes an epidemic shape in Kashmir region. With high prevalence of other comorbid conditions like hypertension, type 2 diabetes, obesity and in conjunction with above nominal prevalence of cigarette and hookah smoking. Majority of both elderly and younger Kashmiri population could contract the disease and show severe symptoms owing to the factors discussed. Here, we summarize the prevalence of hookah smoking among majority of population in Kashmir and the associated lung diseases that are directly or indirectly attributed to high cigarette or hookah smoking in Kashmir and how it could act as high risk factor in COVID pandemic infection.
RSC Advances, 2020
The skin acts as both physical as well as an immunological barrier against hazardous agents from ... more The skin acts as both physical as well as an immunological barrier against hazardous agents from the outside environment and protects the internal organs against damage. Skin ageing is a dynamic process caused by the influence of various external factors, including damage from ultraviolet (UV-B) radiation, which is known as photo-ageing, and due to internal chronological mechanisms. A normal ageing process requires several orchestrated defense mechanisms to diverse types of stress responses, the concomitant renewal of cellular characteristics, and the homeostasis of different cell types that directly or indirectly protect the integrity of skin. Cumulative oxidative and endoplasmic reticulum (ER) stress responses and their adverse impact on biological systems in the skin are a common mechanism of the ageing process, negatively impacting DNA by causing mutations that lead to many physiological, functional, and aesthetic changes in the skin, culminating in the development of many diseases, including photo-damage and photo-carcinogenesis. Exposure of the skin to ultraviolet-(B) elicits the activation of signal transduction pathways, including DNA damage response, autophagy, and checkpoint signal adaptations associated with clearing radiation-induced DNA damage. Recent experimental reports suggest that autophagy is involved in maintaining skin homeostasis upon encountering different stresses, notably genotoxic stress. It has also been revealed that autophagy positively regulates the recognition of DNA damage by nucleotide excision repair and that skin ageing is associated with defects in the autophagy process. Moreover, autophagy is constitutively active in the skin epithelium, imparting protection to skin cells against a diverse range of outside insults, thus increasing resistance to environmental stressors. It has also been found that the stress-induced suppression of the autophagy response in experimental settings leads to enhanced apoptosis during photo-ageing upon UV-B exposure and that the maintenance of homeostasis depends on cellular autophagy levels. More recent reports in this domain claim that relieving the oxidative-stress-mediated induction of the ER stress response upon UV-B irradiation protects skin cells from photo-damage effects. The integration of autophagy and the DNA damage response under genotoxic stress is being considered as a meaningful partnership for finding novel molecular targets and devising suitable therapeutic strategies against photo-ageing disorders. Here, we summarize and review the current understanding of the mechanisms governing the intricate interplay between autophagy and the DNA damage response and its regulation by UV-B, the roles of autophagy in regulating the cellular response to UV-B-induced photodamage, and the implications of the modulation of autophagy as a meaningful partnership in the treatment and prevention of photoaging disorders.
Cellular Physiology and Biochemistry, 2019
Background/Aims: Excessive exposure to UV radiation negatively affects the human skin, characteri... more Background/Aims: Excessive exposure to UV radiation negatively affects the human skin, characterized by photo-damage (premature aging & carcinogenesis). UV-B radiation causes about 90% of non-melanoma skin cancers by damaging de-oxy ribonucleic acids (DNA). We have previously reported that UV-B radiation induces skin photodamage through oxidative & Endoplasmic Reticulum (ER) stresses and Glycyrrhizic acid (GA), a natural triterpene, protects skin cells against such stresses. UV-B radiation elicits signalling cascade by activation of proteins involved in sensing, signalling, and repair process of DNA damage. In this study, we explored the effects & mechanisms of Glycyrrhizic acid (GA) against UV-B –induced photo-damage using a well established cellular model. Methods: We used primary human dermal fibroblasts as a cellular model. The cells were cultured in the presence or absence of GA for 3,6, & 24 h. Effect of UV-B was assessed by examining cell viability, cell morphology, oxidative stress, ER stress, DNA damage & cellular autophagy levels through biochemical assays, microscopy & protein expression studies. Results: In this study, we have determined the effect of GA on autophagy mediated DNA damage response system as the main mechanism in preventing photodamage due to UV-B -irradiation to primary human dermal fibroblasts (HDFs). GA treatment to UV-B exposed HDFs, significantly inhibited cell death,oxidative & ER stress responses, prevented Cyclobutane Pyrimidine dimer (CPD) DNA adduct formation, and DNA fragmentation via modulation of UV-B induced autophagic flux. Present results showed that GA treatment quenched reactive oxygen species (ROS), relieved ER stress response, improved autophagy (6 hr‘s post-UV-B -irradiation) and prevented UV-B induced DNA damage. Conclusion: The present study links autophagy induction by GA as the main mechanism in the prevention of DNA damage and provides a mechanistic basis for the photo-protective effect of GA and suggests that GA can be potentially developed as a promising agent against UV-B induced skin photo-damage.
Journal of Lipid Research, 2017
Defective autophagy has been linked to lipotoxicity in several cellular models. We aimed to inves... more Defective autophagy has been linked to lipotoxicity in several cellular models. We aimed to investigate autophagy in lipid-stimulated hepatoma (Huh7) cells and tested whether 4-phenyl butyric acid (4-PBA), a chemical chaperone, has a beneficial role in hepatic fat accumulation and lipotoxicity. We report that long-term (24 h) exposure of hepatocytes to palmitate block autophagic flux that leads to lipid accumulation and cell death. Western blotting analysis showed increased accumulation of SQSTM1/p62, and decreased expression of Beclin1 and Atg7 in palmitate-treated cells. Autophagy inhibition by 3-methyladenine (3-MA) in palmitate-treated cells neither increased SQSTMI/p62 accumulation nor cell death, thus suggesting complete blockade of autophagy by palmitate. 4-PBA reduced lipid accumulation and cell death that were associated with restoration of autophagy. siRNA-mediated knockdown of Atg7 and presence of autophagy inhibitors, 3-MA and chloroquine, resulted in the decrease in lipid-lowering effect of 4-PBA, suggesting that 4-PBA mediates its lipid-lowering effect via autophagy. Apoptotic parameters, including altered Bcl2:Bax ratio and PARP1 cleavage induced by palmitate, were improved by 4-PBA. Our results indicate that palmitate impairs autophagy and increases lipid accumulation in Huh7 cells, whereas 4-PBA plays a protective role in lipid accumulation and lipotoxicity through activation of autophagy.
Book Chapters by Sheikh Umar Ahmad
CRC Press, Taylor & Francis Group, Apple Academic Press, in Book, The Global Floriculture Industry, 2020
Floriculture industry is currently the fastest-growing biological industry and has taken the fron... more Floriculture industry is currently the fastest-growing biological industry and has taken the front seat when we talk of transgenic flowers of diversified applicability and importance. Whether it be the aroma, scent or for the case oils, new and refined approaches are being constantly explored and tested in development of reliable and affordable floriculturals used in different rituals and on ceremonial occasions. Conventional breeding practices have greatly helped in producing new varieties of flowers with improved aromatic oils and scents. But modern plant biotechnology and genetic engineering tools have greatly improvised the approach in development of novel and quality floricultural produce. Among the diverse range of quality improvisations, consistent efforts are being made to design and conceptualize methodical strategies in developing skin medico cosmetics in flowers itself and can be taken as such or to be utilized in skin ointments and creams in treatment of various skin-related ailments or to increase the antioxidant potential of already existing creams. Newer areas of biotechnology such as genomics, proteomics, and gene mapping have been applied to floricultural plants and have led to the isolation and characterization of genes of potential commercial interest. As on date, there is little scientific literature available that summons the manipulation of candidate genes that directly refer to the use of transgenic floricultural crops for the production of pharmaceuticals or secondary products or as plants in phyto-remediation systems. Producing biomedicines for skin in plants and using it as natural bio-cosmeceutical preparations will help in eliminating the skin tenderness toward the very allergens. Latest gene-editing technologies in which new genes of commercial importance or already known genes with potential properties are being introduced into living systems are edited to further add value to their already existing vigor. From a technology-developer viewpoint, the potential return from research on producing these novel traits in the smaller crops typical in floriculture may be less than it is possible with the “further up the chain” consumer traits, such as the production of flower scent. Nonetheless, it will pave way for the larger interest to the biological community, especially to genetic engineers and biotechnologists to further expand the anticipatory production in these plants. Here, we summarize the current status of research viz-a-viz advancements in modern floriculture industry and scientific efforts to be put in place in producing skin medico cosmetics and phytopharmaceuticals in flowers to be used in the treatment of a range of skin ailments based on hypersensitivity, direct oxidative, and UV damage.
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Research Papers by Sheikh Umar Ahmad
Book Chapters by Sheikh Umar Ahmad