Displaying publications 1 - 20 of 55 in total

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  1. Hemrajani C, Negi P, Parashar A, Gupta G, Jha NK, Singh SK, et al.
    Biomed Pharmacother, 2022 Mar;147:112633.
    PMID: 35030434 DOI: 10.1016/j.biopha.2022.112633
    Atopic dermatitis (AD) is an inflammatory disorder centered around loss of epidermal barrier function, and T helper 2 (Th2) immune responses. The current understanding of disease heterogeneity and complexity, limits the rational use of existing topical, systemic therapeutic agents, but paves way for development of advanced therapeutic agents. Additionally, advanced nanocarriers that deliver therapeutics to target cells, seem to offer a promising strategy, to overcome intrinsic limitations and challenges of conventional, and traditional drug delivery systems. Ever-evolving understanding of molecular target sites and complex pathophysiology, adverse effects of current therapeutic options, inefficient disease recapitulation by existing animal models are some of the challenges that we face. Also, despite limited success in market translatibility, nanocarriers have demonstrated excellent preclinical results and have been extensively studied for AD. Detailed research on behavior of nanocarriers in different patients and tailored therapy to account for phenotypic variability of the disease are the new research avenues that we look forward to.
  2. Prasher P, Sharma M, R Wich P, Jha NK, Singh SK, Chellappan DK, et al.
    Future Med Chem, 2021 12;13(23):2027-2031.
    PMID: 34596425 DOI: 10.4155/fmc-2021-0218
  3. Bhatt S, Devadoss T, Jha NK, Baidya M, Gupta G, Chellappan DK, et al.
    Metab Brain Dis, 2023 Jan;38(1):45-59.
    PMID: 36239867 DOI: 10.1007/s11011-022-01095-1
    Major depressive disorder (MDD) or Depression is one of the serious neuropsychiatric disorders affecting over 280 million people worldwide. It is 4th important cause of disability, poor quality of life, and economic burden. Women are more affected with the depression as compared to men and severe depression can lead to suicide. Most of the antidepressants predominantly work through the modulation on the availability of monoaminergic neurotransmitter (NTs) levels in the synapse. Current antidepressants have limited efficacy and tolerability. Moreover, treatment resistant depression (TRD) is one of the main causes for failure of standard marketed antidepressants. Recently, inflammation has also emerged as a crucial factor in pathological progression of depression. Proinflammatory cytokine levels are increased in depressive patients. Antidepressant treatment may attenuate depression via modulation of pathways of inflammation, transformation in structure of brain, and synaptic plasticity. Hence, targeting inflammation may be emerged as an effective approach for the treatment of depression. The present review article will focus on the preclinical and clinical studies that targets inflammation. In addition, it also concentrates on the therapeutic approaches' that targets depression via influence on the inflammatory signaling pathways. Graphical abstract demonstrate the role of various factors in the progression and neuroinflammation, oxidative stress. It also exhibits the association of neuroinflammation, oxidative stress with depression.
  4. Gundamaraju R, Wu J, William JNG, Lu W, Jha NK, Ramasamy S, et al.
    Biotechnol Genet Eng Rev, 2023 Apr;39(1):143-165.
    PMID: 35904341 DOI: 10.1080/02648725.2022.2106002
    Glioblastoma (GBM) is presented with a poor prognosis. The endoplasmic reticulum stress (ERS) has been implicated as a major contributor to disease progression and chemoresistance in GBM. Triggering ERS by chemical agents or genetic modulations is identified as some of the reasons for regulating gene expression and the pathogenesis of GBM. ERS initiates unfolded protein response (UPR), an integrated system useful in restoring homeostasis or inducing apoptosis. Modulation of UPR might have positive outcomes in GBM treatment as UPR inducers have been shown to alter cell survival and migration. In the current review, we have utilized GSE7806, a publicly available dataset from Gene Expression Omnibus (GEO), to evaluate the genes expressed during 6.5 hr and 18 hr, which can be comparable to the early and late-onset of the disease. Subsequently, we have elucidated the prognosis and survival information whilst the expression of these genes in the GBM was noted in previous studies. This is the first of its kind review summarizing the most recent gene information correlating UPR and GBM.
  5. Prasher P, Sharma M, Chellappan DK, Gupta G, Jha NK, Singh SK, et al.
    Future Med Chem, 2021 07;13(13):1087-1090.
    PMID: 33947226 DOI: 10.4155/fmc-2021-0013
  6. Gupta G, Chellappan DK, Singh SK, Gupta PK, Kesari KK, Jha NK, et al.
    Nanomedicine (Lond), 2021 10;16(25):2243-2247.
    PMID: 34547920 DOI: 10.2217/nnm-2021-0254
  7. Chellappan DK, Dharwal V, Paudel KR, Jha NK, MacLoughlin R, Oliver BG, et al.
    Future Med Chem, 2021 08;13(15):1249-1251.
    PMID: 34184585 DOI: 10.4155/fmc-2021-0097
  8. Devkota HP, Paudel KR, Jha NK, Gupta PK, Singh SK, Chellappan DK, et al.
    Nanomedicine (Lond), 2021 11;16(27):2407-2410.
    PMID: 34670398 DOI: 10.2217/nnm-2021-0275
  9. Prasher P, Sharma M, Chan Y, Singh SK, Anand K, Dureja H, et al.
    Curr Med Chem, 2023;30(13):1529-1567.
    PMID: 34766883 DOI: 10.2174/0929867328666211111161811
    Protein kinases modulate the structure and function of proteins by adding phosphate groups to threonine, tyrosine, and serine residues. The phosphorylation process mediated by the kinases regulates several physiological processes, while their overexpression results in the development of chronic diseases, including cancer. Targeting of receptor tyrosine kinase pathways results in the inhibition of angiogenesis and cell proliferation that validates kinases as a key target in the management of aggressive cancers. As such, the identification of protein kinase inhibitors revolutionized the contemporary anticancer therapy by inducing a paradigm shift in the management of disease pathogenesis. Contemporary drug design programs focus on a broad range of kinase targets for the development of novel pharmacophores to manage the overexpression of kinases and their pathophysiology in cancer pathogenesis. In this review, we present the emerging trends in the development of rationally designed molecular inhibitors of kinases over the last five years (2016-2021) and their incipient role in the development of impending anticancer pharmaceuticals.
  10. Masanam HB, Perumal G, Krishnan S, Singh SK, Jha NK, Chellappan DK, et al.
    Nanomedicine (Lond), 2022 Oct;17(25):1981-2005.
    PMID: 36695290 DOI: 10.2217/nnm-2021-0427
    The development of rapid, noninvasive diagnostics to detect lung diseases is a great need after the COVID-2019 outbreak. The nanotechnology-based approach has improved imaging and facilitates the early diagnosis of inflammatory lung diseases. The multifunctional properties of nanoprobes enable better spatial-temporal resolution and a high signal-to-noise ratio in imaging. Targeted nanoimaging agents have been used to bind specific tissues in inflammatory lungs for early-stage diagnosis. However, nanobased imaging approaches for inflammatory lung diseases are still in their infancy. This review provides a solution-focused approach to exploring medical imaging technologies and nanoprobes for the detection of inflammatory lung diseases. Prospects for the development of contrast agents for lung disease detection are also discussed.
  11. Garg J, Chiu MN, Krishnan S, Kumar R, Rifah M, Ahlawat P, et al.
    Appl Biochem Biotechnol, 2024 Feb;196(2):1008-1043.
    PMID: 37314636 DOI: 10.1007/s12010-023-04570-2
    Over the last few decades, the application of nanoparticles (NPs) gained immense attention towards environmental and biomedical applications. NPs are ultra-small particles having size ranges from 1 to 100 nm. NPs loaded with therapeutic or imaging compounds have proved a versatile approach towards healthcare improvements. Among various inorganic NPs, zinc ferrite (ZnFe2O4) NPs are considered as non-toxic and having an improved drug delivery characteristics . Several studies have reported broader applications of ZnFe2O4 NPs for treating carcinoma and various infectious diseases. Additionally, these NPs are beneficial for reducing organic and inorganic environmental pollutants. This review discusses about various methods to fabricate ZnFe2O4 NPs and their physicochemical properties. Further, their biomedical and environmental applications have also been explored comprehensively.
  12. Sharma A, Hawthorne S, Jha SK, Jha NK, Kumar D, Girgis S, et al.
    Nanomedicine (Lond), 2021 08;16(20):1763-1773.
    PMID: 34296625 DOI: 10.2217/nnm-2021-0066
    Aim: This study was aimed at evaluating the anticancer potential of curcumin-loaded poly(lactic-co-glycolic acid) (PLGA) based nanoparticles (NPs) in MDA-MB231 human breast cancer cells. Methods: Curcumin-loaded PLGA NPs were developed using a modified solvent evaporation technique. Physical characterization was performed on the formulated NPs. Furthermore, in vitro experiments were conducted to study the biological activity of the curcumin-loaded NPs. Results: Curcumin-loaded PLGA NPs demonstrated high encapsulation efficiency and sustained payload release. Moreover, the NPs exhibited a significant reduction in cell viability, cell migration and cell invasion in the MDA-MB231 cells. Conclusion: The study revealed that the formulated curcumin-loaded PLGA NPs possessed significant anti-metastatic properties. The findings showcased the possible potential of curcumin-loaded NPs in the management of debilitating conditions such as cancer. In addition, this study could form the basis for further research and advancements in this area.
  13. Corrie L, Gulati M, Singh SK, Kapoor B, Khursheed R, Awasthi A, et al.
    Life Sci, 2021 Sep 01;280:119753.
    PMID: 34171379 DOI: 10.1016/j.lfs.2021.119753
    Polycystic ovarian syndrome (PCOS) is the primary cause of female infertility affecting several women worldwide. Changes in hormonal functions such as hyperandrogenism are considered a significant factor in developing PCOS in women. In addition, many molecular pathways are involved in the pathogenesis of PCOS in women. To have better insights about PCOS, it is data from clinical studies carried on women suffering from PCOS should be collected. However, this approach has several implications, including ethical considerations, cost involved and availability of subject. Moreover, during the early drug development process, it is always advisable to use non-human models mimicking human physiology as they are less expensive, readily available, have a shorter gestation period and less risk involved. Many animal models have been reported that resemble the PCOS pathways in human subjects. However, the models developed on rats and mice are more preferred over other rodent/non-rodent models due to their closer resemblance with human PCOS development mechanism. The most extensively reported PCOS models for rats and mice include those induced by using testosterone, letrozole and estradiol valerate. As the pathophysiology of PCOS is complex, none of the explored models completely surrogates the PCOS related conditions occurring in women. Hence, there is a need to develop an animal model that can resemble the pathophysiology of PCOS in women. The review focuses on various animal models explored to understand the pathophysiology of PCOS. The article also highlights some environmental and food-related models that have been used to induce PCOS.
  14. Shastri MD, Allam VSRR, Shukla SD, Jha NK, Paudel KR, Peterson GM, et al.
    Life Sci, 2021 Oct 15;283:119871.
    PMID: 34352260 DOI: 10.1016/j.lfs.2021.119871
    Non-communicable, chronic respiratory diseases (CRDs) affect millions of individuals worldwide. The course of these CRDs (asthma, chronic obstructive pulmonary disease, and cystic fibrosis) are often punctuated by microbial infections that may result in hospitalization and are associated with increased risk of morbidity and mortality, as well as reduced quality of life. Interleukin-13 (IL-13) is a key protein that regulates airway inflammation and mucus hypersecretion. There has been much interest in IL-13 from the last two decades. This cytokine is believed to play a decisive role in the exacerbation of inflammation during the course of viral infections, especially, in those with pre-existing CRDs. Here, we discuss the common viral infections in CRDs, as well as the potential role that IL-13 plays in the virus-induced disease pathogenesis of CRDs. We also discuss, in detail, the immune-modulation potential of IL-13 that could be translated to in-depth studies to develop IL-13-based therapeutic entities.
  15. Jha NK, Sharma A, Jha SK, Ojha S, Chellappan DK, Gupta G, et al.
    Open Biol, 2020 12;10(12):200286.
    PMID: 33352062 DOI: 10.1098/rsob.200286
    Excessive exposure to toxic substances or chemicals in the environment and various pathogens, including viruses and bacteria, is associated with the onset of numerous brain abnormalities. Among them, pathogens, specifically viruses, elicit persistent inflammation that plays a major role in Alzheimer's disease (AD) as well as dementia. AD is the most common brain disorder that affects thought, speech, memory and ability to execute daily routines. It is also manifested by progressive synaptic impairment and neurodegeneration, which eventually leads to dementia following the accumulation of Aβ and hyperphosphorylated Tau. Numerous factors contribute to the pathogenesis of AD, including neuroinflammation associated with pathogens, and specifically viruses. The human immunodeficiency virus (HIV) is often linked with HIV-associated neurocognitive disorders (HAND) following permeation through the blood-brain barrier (BBB) and induction of persistent neuroinflammation. Further, HIV infections also exhibited the ability to modulate numerous AD-associated factors such as BBB regulators, members of stress-related pathways as well as the amyloid and Tau pathways that lead to the formation of amyloid plaques or neurofibrillary tangles accumulation. Studies regarding the role of HIV in HAND and AD are still in infancy, and potential link or mechanism between both is not yet established. Thus, in the present article, we attempt to discuss various molecular mechanisms that contribute to the basic understanding of the role of HIV-associated neuroinflammation in AD and HAND. Further, using numerous growth factors and drugs, we also present possible therapeutic strategies to curb the neuroinflammatory changes and its associated sequels.
  16. Khursheed R, Singh SK, Wadhwa S, Gulati M, Kapoor B, Jain SK, et al.
    Int J Biol Macromol, 2021 Oct 31;189:744-757.
    PMID: 34464640 DOI: 10.1016/j.ijbiomac.2021.08.170
    The role of mushroom polysaccharides and probiotics as pharmaceutical excipients for development of nanocarriers has never been explored. In the present study an attempt has been made to explore Ganoderma lucidum extract powder (GLEP) containing polysaccharides and probiotics to convert liquid self nanoemulsifying drug delivery system (SNEDDS) into solid free flowing powder. Two lipophilic drugs, curcumin and quercetin were used in this study due to their dissolution rate limited oral bioavailability and poor permeability. These were loaded into liquid SNEDDS by dissolving them into isotropic mixture of Labrafill M1944CS, Capmul MCM, Tween-80 and Transcutol P. The liquid SNEDDS were solidified using probiotics and mushroom polysaccharides as carriers and Aerosil-200 as coating agent. The solidification was carried out using spray drying process. The process and formulation variables for spray drying process of liquid SNEDDS were optimized using Box Behnken Design to attain required powder properties. The release of both drugs from the optimized spray dried (SD) formulation was found to be more than 90%, whereas, it was less than 20% for unprocessed drugs. The results of DSC, PXRD and SEM, showed that the developed L-SNEDDS preconcentrate was successfully loaded onto the porous surface of probiotics, mushroom polysaccharides and Aerosil-200.
  17. Faiyaz M, Ganayee MA, Akhtar S, Krishnan S, Flora B, Dogra D, et al.
    Front Biosci (Landmark Ed), 2021 10 30;26(10):851-865.
    PMID: 34719210 DOI: 10.52586/4992
    Alzheimer's, a progressive neurodegenerative disease affects brain and neurons through enormous reduction in nerve cell regenerative capacity. Dementia and impairment of cognitive functions are more prevalent in Alzheimer's disease (AD) patients in both industrialized and non-industrialized countries. Various factors play significant role in molecular cascades that leads to neuronal inflammation, dementia and thereby AD progression. Current medications are symptomatic that alleviates pain while lack in absolute cure, urging researchers to explore targets and therapeutics. Interestingly, nanomedicines developed due to the onset of nanotechnology, are being extensively investigated for the treatment of AD. This review presents the advancement in nanotherapeutic strategies, involving the emergence of nanomaterials that offers advantage to pass through the blood-brain barrier and acts as a therapeutic modality against AD.
  18. Kadukkattil Ramanunny A, Singh SK, Wadhwa S, Gulati M, Kapoor B, Khursheed R, et al.
    Expert Opin Drug Deliv, 2022 Jan;19(1):23-45.
    PMID: 34913772 DOI: 10.1080/17425247.2022.2019218
    INTRODUCTION: Non-aqueous nano-emulsions (NANEs) are colloidal lipid-based dispersions with nano-sized droplets formed by mixing two immiscible phases, none of which happens to be an aqueous phase. Their ability to incorporate water and oxygen sensitive drugs without any susceptibility to degradation makes them the optimum dosage form for such candidates. In NANEs, polar liquids or polyols replace the aqueous phase while surfactants remain same as used in conventional emulsions. They are a part of the nano-emulsion family albeit with substantial difference in composition and application.

    AREAS COVERED: The present review provides a brief insight into the strategies of loading water-sensitive drugs into NANEs. Further advancement in these anhydrous systems with the use of solid particulate surfactants in the form of Pickering emulsions is also discussed.

    EXPERT OPINION: NANEs offer a unique platform for delivering water-sensitive drugs by loading them in anhydrous formulation. The biggest advantage of NANEs vis-à-vis the other nano-cargos is that they can also be prepared without using equipment-intensive techniques. However, the use of NANEs in drug delivery is quite limited. Looking at the small number of studies available in this direction, a need for further research in this field is required to explore this delivery system further.

  19. Rohilla S, Singh M, Priya S, Almalki WH, Haniffa SM, Subramaniyan V, et al.
    PMID: 36734949 DOI: 10.1615/JEnvironPatholToxicolOncol.2022042088
    Melatonin is a serotonin-derived pineal gland hormone with many biological functions like regulating the sleep-wake cycle, circadian rhythm, menstrual cycle, aging, immunity, and antioxidants. Melatonin synthesis and release are more pronounced during the night, whereas exposure to light decreases it. Evidence is mounting in favor of the therapeutic effects of melatonin in cancer prevention, treatment and delayed onset in various cancer subtypes. Melatonin exerts its anticancer effect through modification of its receptors such as melatonin 1 (MT1), melatonin 2 (MT2), and inhibition of cancer cell proliferation, epigenetic alterations (DNA methylation/demethylation, histone acetylation/deacetylation), metastasis, angiogenesis, altered cellular energetics, and immune evasion. Melatonin performs a significant function in immune modulation and enhances innate and cellular immunity. In addition, melatonin has a remarkable impact on epigenetic modulation of gene expression and alters the transcription of genes. As an adjuvant to cancer therapies, it acts by decreasing the side effects and boosting the therapeutic effects of chemotherapy. Since current treatments produce drug-induced unwanted toxicities and side effects, they require alternate therapies. A recent review article attempts to summarize the mechanistic perspective of melatonin in different cancer subtypes like skin cancer, breast cancer, hepatic cancer, renal cell cancer, non-small cell lung cancer (NSCLC), colon oral, neck, and head cancer. The various studies described in this review will give a firm basis for the future evolution of anticancer drugs.
  20. Kaur J, Gulati M, Corrie L, Awasthi A, Jha NK, Chellappan DK, et al.
    Nanomedicine (Lond), 2022 Oct;17(25):1951-1960.
    PMID: 36606499 DOI: 10.2217/nnm-2022-0260
    The prevalence of lung diseases is increasing year by year and existing drug therapies only provide symptomatic relief rather than targeting the actual cause. Nucleic acids can be used as an alternative therapeutic approach owing to their potential to reform a homeostatic balance by upregulating protective genes or downregulating damaging genes. However, their inherent properties, such as poor stability, ineffective cellular uptake, negative charge and so on, hinder their clinical utility. Such limitations can be overcome by exploiting the functional chemistry of polymeric micelles (PMs) for site-specific delivery, transfection efficiency and improved stability. With this objective, the present work describes the advancements made in designing nucleic acid-based PMs for treating lung diseases followed by approaches requiring consideration for clinical applications.
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