Displaying publications 41 - 60 of 284 in total

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  1. Waghule T, Sankar S, Rapalli VK, Gorantla S, Dubey SK, Chellappan DK, et al.
    Dermatol Ther, 2020 11;33(6):e13905.
    PMID: 32588940 DOI: 10.1111/dth.13905
    The incidences of fungal infections have greatly increased over the past few years, particularly in humid and industrialized areas. The severity of such infections ranges from being asymptomatic-mild to potentially life-threatening systemic infections. There are limited classes of drugs that are approved for the treatment of such infections like polyenes, azoles, and echinocandins. Some fungi have developed resistance to these drugs. Therefore, to counter drug resistance, intensive large scale studies on novel targeting strategies and formulations are being conducted, which have gained impetus lately. Conventional formulations have limitations such as higher doses, frequent dosing, and several side effects. Such limiting factors have paved the path for the emergence of nanotechnology and its applications. This further gave formulation scientists the possibility of encapsulating the existing potential drug moieties into nanocarriers, which when loaded into gels or creams provided prolonged release and improved permeation, thus giving on-target effect. This review thus discusses the newer targeting strategies and the role of nanocarriers that could be administered topically for the treatment of various fungal infections. Furthermore, this approach opens newer avenues for continued and sustained research in pharmaceuticals with much more effective outcomes.
  2. Chan Y, Ng SW, Mehta M, Anand K, Kumar Singh S, Gupta G, et al.
    Med Hypotheses, 2020 Nov;144:110298.
    PMID: 33254489 DOI: 10.1016/j.mehy.2020.110298
    Outbreaks of influenza infections in the past have severely impacted global health and socioeconomic growth. Antivirals and vaccines are remarkable medical innovations that have been successful in reducing the rates of morbidity and mortality from this disease. However, the relentless emergence of drug resistance has led to a worrisome increase in the trend of influenza outbreaks, characterized by worsened clinical outcomes as well as increased economic burden. This has prompted the need for breakthrough innovations that can effectively manage influenza outbreaks. This article provides an insight into a novel hypothesis that describes how the integration of nanomedicine, with the development of drugs and vaccines can potentially enhance body immune response and the efficacies of anti-viral therapeutics to combat influenza infections.
  3. Pathak S, Gupta G, Thangavelu L, Singh SK, Dua K, Chellappan DK, et al.
    EXCLI J, 2021;20:1028-1032.
    PMID: 34267614 DOI: 10.17179/excli2021-3687
  4. Gupta G, Bebawy M, Pinto TJA, Chellappan DK, Mishra A, Dua K
    Crit Rev Eukaryot Gene Expr, 2018;28(3):217-221.
    PMID: 30311568 DOI: 10.1615/CritRevEukaryotGeneExpr.2018021188
    Cancer is a complicated transformational progression that fiercely changes the appearance of cell physiology as well as cells' relations with adjacent tissues. Developing an oncogenic characteristic requires a wide range of modifications in a gene expression at a cellular level. This can be achieved by activation or suppression of the gene regulation pathway in a cell. Tristetraprolin (TTP or ZFP36) associated with the initiation and development of tumors are regulated at the level of mRNA decay, frequently through the activity of AU-rich mRNA-destabilizing elements (AREs) located in their 3'-untranslated regions. TTP is an attractive target for therapeutic use and diagnostic tools due to its characteristic appearance in cancer tissue alone. Thus, the illumination of TTP in diverse types of cancer might deliver additional effective remedies in the coming era for cancer patients. The objective of this review is to familiarize the reader with the TTP proteins, focus on efficient properties that endow them with their effective oncogenic potential, describe their physiological role in cancer cells, and review the unique properties of TT, and of TTP-driven cancer.
  5. Chan Y, Ng SW, Mehta M, Gupta G, Chellappan DK, Dua K
    Future Med Chem, 2020 11;12(21):1887-1890.
    PMID: 33054387 DOI: 10.4155/fmc-2020-0206
  6. Singhvi G, Patil S, Girdhar V, Chellappan DK, Gupta G, Dua K
    Panminerva Med, 2018 Dec;60(4):170-173.
    PMID: 29856179 DOI: 10.23736/S0031-0808.18.03467-5
    One of the novel and progressive technology employed in pharmaceutical manufacturing, design of medical device and tissue engineering is three-dimensional (3D) printing. 3D printing technologies provide great advantages in 3D scaffolds fabrication over traditional methods in the control of pore size, porosity, and interconnectivity. Various techniques of 3D-printing include powder bed fusion, fused deposition modeling, binder deposition, inkjet printing, photopolymerization and many others which are still evolving. 3D-printing technique been employed in developing immediate release products, various systems to deliver multiple release modalities etc. 3D printing has opened the door for new generation of customized drug delivery with built-in flexibility for safer and effective therapy. Our mini-review provides a quick snapshot on an overview of 3D printing, various techniques employed, applications and its advancements in pharmaceutical sciences.
  7. Rapalli VK, Singhvi G, Dubey SK, Gupta G, Chellappan DK, Dua K
    Biomed Pharmacother, 2018 Oct;106:707-713.
    PMID: 29990862 DOI: 10.1016/j.biopha.2018.06.136
    Psoriasis is a chronic autoimmune skin disorder affecting 2-3% of the world population. It has characteristic features such as increased keratinocyte proliferation and production of inflammatory mediators. The treatment involves various strategies including topical, systemic, phototherapy and biologics. Topical therapies are preferred for mild to moderate psoriasis conditions over the systemic therapies which are ideal in severe disease conditions. The systemic therapies include immunosuppressants, biological agents and recently approved phosphodiesterase-4 (PDE4) inhibitors. There are various limitations associated with the existing therapies where the new findings in the pathogenesis of psoriasis are paving a path for newer therapeutics to target at the molecular level. Various small molecules, PDE-4 inhibitors, biologics, and immunomodulator proved efficacious including the new molecules targeting Janus kinases (JAK) inhibitors that are under investigation. Furthermore, the role of genetic and miRNAs in psoriasis is still not completely explored and may further help in improving the treatment efficacy. This review provides an insight into various emerging therapies along with currently approved treatments for psoriasis.
  8. Soni N, Tekade M, Kesharwani P, Bhattacharya P, Maheshwari R, Dua K, et al.
    Curr Pharm Des, 2017 08 30;23(21):3084-3098.
    PMID: 28356042 DOI: 10.2174/1381612823666170329150201
    BACKGROUND: Disseminated metastatic cancer requires insistent management owing to its reduced responsiveness for chemotherapeutic agents, toxicity to normal cells consequently lower survival rate and hampered quality of life of patients.

    METHODS: Dendrimer mediated cancer therapy is advantageous over conventional chemotherapy, radiotherapy and surgical resection due to reduced systemic toxicity, and molecular level cell injury to cancerous mass, for an appreciable survival of the subject. Recently used dendrimer mediated nanotechnology for oncology aims to conquer these challenges. Dendrimers based nano-constructs are having architectures comparable to that of biological vesicles present in the human body.

    RESULTS: Operating with dendrimer technology, proffers the exclusive and novel strategies with numerous applications in cancer management involving diagnostics, therapeutics, imaging, and prognostics by sub-molecular interactions. Dendrimers are designed to acquire the benefits of the malignant tumor morphology and characteristics, i.e. leaky vasculature of tumor, expression of specific cell surface antigen, and rapid proliferation.

    CONCLUSION: Dendrimers mediated targeted therapy recommends innovatory function equally in diagnostics (imaging, immune-detection) as well as chemotherapy. Currently, dendrimers as nanomedicine has offered a strong assurance and advancement in drastically varying approaches towards cancer imaging and treatment. The present review discusses different approaches for cancer diagnosis and treatment such as, targeted and control therapy, photodynamic therapy, photo-thermal therapy, gene therapy, antiangiogenics therapy, radiotherapy etc.

  9. Awasthi R, Singh AK, Mishra G, Maurya A, Chellappan DK, Gupta G, et al.
    Adv Exp Med Biol, 2018 9 28;1087:3-14.
    PMID: 30259353 DOI: 10.1007/978-981-13-1426-1_1
    Circular RNAs (cirRNAs) are long, noncoding endogenous RNA molecules and covalently closed continuous loop without 5'-3' polarity and polyadenylated tail which are largely concentrated in the nucleus. CirRNA regulates gene expression by modulating microRNAs and functions as potential biomarker. CirRNAs can translate in vivo to link between their expression and disease. They are resistant to RNA exonuclease and can convert to the linear RNA by microRNA which can then act as competitor to endogenous RNA. This chapter summarizes the evolutionary conservation and expression of cirRNAs, their identification, highlighting various computational approaches on cirRNA, and translation with a focus on the breakthroughs and the challenges in this new field.
  10. Balusamy SR, Veerappan K, Ranjan A, Kim YJ, Chellappan DK, Dua K, et al.
    Phytomedicine, 2019 Oct 31;66:153129.
    PMID: 31794911 DOI: 10.1016/j.phymed.2019.153129
    BACKGROUND: Phyllanthus emblica L. (Indian gooseberry) is widely used in the Ayurveda for thousands of years to treat health complications including disorders of the immune system, diabetes, and obesity.

    PURPOSE: For the first time, our study aims to demonstrate the molecular mechanisms of the fruit extract of Phyllanthus emblica (PEFE) involved in the promotion of fat cell apoptosis and alleviation of adipogenesis.

    METHODS: The active constituents from PEFE were identified using high performance liquid chromatography-mass spectrometry (HPLC-MS). We carried out the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay to evaluate the cytotoxic effects of PEFE using 3T3-L1 pre-adipocytes. The colonogenic assay was carried out to determine the inhibitory effect of 3T3-L1 adipocytes after PEFE treatment. In addition, inhibition of pancreatic lipase activity was performed and the lipolytic activity of PEFE and digallic acid was compared with the well-known standard drug orlistat. Besides, the molecular interaction and ligand optimization between digallic and adipogenesis/apoptosis markers were also carried out. Furthermore, to confirm fat cell apoptosis we have used several detection methods that includes Hoechst staining, PI staining, Oil staining and qPCR respectively.

    RESULTS: Digallic acid was identified as a major component in the PEFE. The IC50 values of digallic acid and PEFE were found to be 3.82 µg/ml and 21.85 µg/ml respectively. PEFE and digallic acid showed significant anti-lipolytic activity compared to the standard drug orlistat. In the mature adipocytes, PEFE significantly decreased triglyceride accumulation by downregulating adiponectin, PPARγ, cEBPα, and FABP4 respectively. We further analyzed the expression of apoptosis related genes upon PEFE treatment. Apoptotic process initiated through upregulation of BAX and downregulation of BCL2 resulting in an increased caspase-3 activity. In addition, we have also confirmed the apoptosis and DNA fragmentation in 3T3-L1 cells using Hoechst, PI and TUNEL assays.

    CONCLUSION: PEFE negatively regulates adipogenesis by initiating fat cell apoptosis and therefore it can be considered as a potential herbal medicinal product for treating obesity.

  11. Dighe SN, Ekwudu O, Dua K, Chellappan DK, Katavic PL, Collet TA
    Eur J Med Chem, 2019 Aug 15;176:431-455.
    PMID: 31128447 DOI: 10.1016/j.ejmech.2019.05.010
    Dengue is the most important arthropod-borne viral disease of humans, with more than half of the global population living in at-risk areas. Despite the negative impact on public health, there are no antiviral therapies available, and the only licensed vaccine, Dengvaxia®, has been contraindicated in children below nine years of age. In an effort to combat dengue, several small molecules have entered into human clinical trials. Here, we review anti-DENV molecules and their drug targets that have been published within the past five years (2014-2018). Further, we discuss their probable mechanisms of action and describe a role for classes of clinically approved drugs and also an unclassified class of anti-DENV agents. This review aims to enhance our understanding of novel agents and their cognate targets in furthering innovations in the use of small molecules for dengue drug therapies.
  12. Gautam RK, Gupta G, Sharma S, Hatware K, Patil K, Sharma K, et al.
    Int J Rheum Dis, 2019 Jul;22(7):1247-1254.
    PMID: 31155849 DOI: 10.1111/1756-185X.13602
    AIM: The purpose of our investigation is to evaluate the anti-arthritic potential of isolated rosmarinic acid from the rind of Punica granatum.

    METHOD: Rosmarinic acid was isolated by bioactivity-guided isolation from butanolic fraction of Punica granatum and acute toxicity of rosmarinic acid was carried out. The experiment was conducted at doses of 25 and 50 mg/kg, in Freund's complete adjuvant (FCA)-induced arthritic rats. Various parameters, that is arthritic score, paw volume, thickness of paw, hematological, antioxidant and inflammatory parameters such as glutathione (GSH), superoxide dismutase (SOD), malonaldehyde (MDA) and tumor necrosis factor-α (TNF-α) were also estimated.

    RESULTS: Rosmarinic acid significantly decreased the arthritic score, paw volume, joint diameter, white blood cell count and erythrocyte sedimentation rate. It also significantly increased body weight, hemoglobin and red blood cells. The significantly decreased levels of TNF-α were observed in treated groups as compared to arthritic control rats (P 

  13. Singh Y, Gupta G, Satija S, Pabreja K, Chellappan DK, Dua K
    Drug Dev Res, 2020 09;81(6):647-649.
    PMID: 32329083 DOI: 10.1002/ddr.21674
  14. Singh Y, Gupta G, Satija S, Negi P, Chellappan DK, Dua K
    Dermatol Ther, 2020 Jul;33(4):e13501.
    PMID: 32359088 DOI: 10.1111/dth.13501
  15. 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.
  16. Samuel VP, Dahiya R, Singh Y, Gupta G, Sah SK, Gubbiyappa SK, et al.
    J Environ Pathol Toxicol Oncol, 2019;38(2):133-141.
    PMID: 31679276 DOI: 10.1615/JEnvironPatholToxicolOncol.2019029388
    The current study is a review of the literature on patients with diabetes who are diagnosed with colorectal cancer (CRC), encompassing recent research on CRC and the molecular level changes occurring in these patients on the basis of varying environmental as well as non-environmental factors. It has been noted that nearly 50% of all patients undergo the systemic treatment module; however, most of them exhibit drug resistance. In addition, targeted gene therapy has also been used in treatment but has been found to be effective only in patients with a specified molecular profile (or else this might lead to an increased risk of developing resistant mutations). This has led to increasing interest among researchers in finding innovative treatment options. Metformin, a biguanide, has been widely used in treating diabetes. The drug has been reportedly used in cases of hypothesis-generating retrospective population studies of diabetic patients showing reduced incidence of cancer. Metformin helps in reduction of excess insulin levels that possess various effects on cell signaling and metabolism. Nonetheless, there is need for an in-depth study on its molecular mechanism to fill any existing research gaps.
  17. Gupta G, Krishna G, Chellappan DK, Gubbiyappa KS, Candasamy M, Dua K
    Mol Cell Biochem, 2014 Aug;393(1-2):223-8.
    PMID: 24771068 DOI: 10.1007/s11010-014-2064-9
    Acetaminophen has a reasonable safety profile when consumed in therapeutic doses. However, it could induce hepatotoxicity and even acute liver failure when taken at an overdose. Pioglitazone, PPARγ ligand, is clinically tested and used in treatment of diabetes. PPARγ is a key nuclear hormone receptor of lipid metabolisms and regulates several gene transcriptions associated with differentiation, growth arrest, and apoptosis. The aim of our study was to evaluate the hepatoprotective activity of pioglitazone on acetaminophen-induced hepatotoxicity and to understand the relationship between the PPARγ and acetaminophen-induced hepato injury. For the experiment, Sprague-Dawley rats (160-180 g) were used and divided into four groups. Groups I and II were normal and experimental controls, respectively. Groups III and IV received the pioglitazone 20 mg/kg for 10 days. Hepatotoxicity was induced in Groups II and III on the eighth day with acetaminophen (i.p. 350 mg/kg body weight). The hepatoprotective effect was evaluated by performing an assay of the total protein, total bilirubin, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, and α-fetoprotein as well as glutathione peroxidase, lipid peroxidation, catalase, superoxide dismutase, and glutathione transferase and liver histopathology. The assay results were presented as mean and standard error of mean for each group. The study group was compared with the control group by one-way ANOVA test. A p value of <0.05 was considered significant. Pioglitazone significantly reduced the elevated level of above serum marker enzymes and also inhibits the free radical formation by scavenging hydroxyl ions. It also restored the level of LPO and significantly elevated the levels of endogenous antioxidant enzymes in acetaminophen-challenged hepatotoxicity. Liver histopathological examination showed that pioglitazone administration antagonized acetaminophen -induced liver pathological damage. Various biochemical estimations of different hepatic markers and antioxidant enzymes and histopathological studies of liver tissues glimpse a support to its significant hepatoprotective activity on acetaminophen -induced hepatotoxicity.
  18. Mehta M, Malyla V, Paudel KR, Chellappan DK, Hansbro PM, Oliver BG, et al.
    J Food Biochem, 2021 11;45(11):e13954.
    PMID: 34609010 DOI: 10.1111/jfbc.13954
    Metastasis represents the leading cause of death in lung cancer patients. C-X-C Motif Chemokine Ligand 8 (CXCL-8), Chemokine (C-C motif) ligand 20 (CCL-20) and heme oxygenase -1 (HO-1) play an important role in cancer cell proliferation and migration. Berberine is an isoquinoline alkaloid isolated from several herbs in the Papaveraceae family that exhibits anti-inflammatory, anticancer and antidiabetic properties. Therefore, the aim of present study is to investigate the inhibitory potential of berberine monoolein loaded liquid crystalline nanoparticles (berberine-LCNs) against cancer progression. Berberine-LCNs were prepared by mixing berberine, monoolein and poloxamer 407 (P407) using ultrasonication method. A549 cells were treated with or without 5 µM dose of berberine LCNs for 24 hr and total cellular protein was extracted and further analyzed for the protein expression of CCl-20, CXCL-8 and HO-1 using human oncology array kit. Our results showed that berberine-LCNs significantly reduced the expression of CCl-20, CXCL-8 and HO-1 at dose of 5µM. Collectively, our findings suggest that berberine-LCNs have inhibitory effect on inflammation/oxidative stress related cytokines i.e. CCL20, CXCL-8, and HO-1 which could be a novel therapeutic target for the management of lung cancer. PRACTICAL APPLICATIONS: Berberine is an isoquinoline alkaloid extracted from various plants of Papaveraceae family. CXCL-8, CCL-20 and HO-1 play an important role in cancer progression. Our study showed that Berberine LCNs significantly downregulate the expression of CXCL-8, CCL-20 and HO-1 which suggests that Berberine loaded nanoparticles could be a promising therapeutic alternative for the management of lung cancer.
  19. Sharma A, Sethi G, Tambuwala MM, Aljabali AAA, Chellappan DK, Dua K, et al.
    Curr Neuropharmacol, 2021;19(2):248-264.
    PMID: 32348224 DOI: 10.2174/1570159X18666200429013041
    All mammalian cells exhibit circadian rhythm in cellular metabolism and energetics. Autonomous cellular clocks are modulated by various pathways that are essential for robust time keeping. In addition to the canonical transcriptional translational feedback loop, several new pathways of circadian timekeeping - non-transcriptional oscillations, post-translational modifications, epigenetics and cellular signaling in the circadian clock - have been identified. The physiology of circadian rhythm is expansive, and its link to the neurodegeneration is multifactorial. Circadian rhythm disruption is prevelant in contamporary society where light-noise, shift-work, and transmeridian travel are commonplace, and is also reported from the early stages of Alzheimer's disease (AD). Circadian alignment by bright light therapy in conjunction with chronobiotics is beneficial for treating sundowning syndrome and other cognitive symptoms in advanced AD patients. We performed a comprehensive analysis of the clinical and translational reports to review the physiology of the circadian clock, delineate its dysfunction in AD, and unravel the dynamics of the vicious cycle between two pathologies. The review delineates the role of putative targets like clock proteins PER, CLOCK, BMAL1, ROR, and clock-controlled proteins like AVP, SIRT1, FOXO, and PK2 towards future approaches for management of AD. Furthermore, the role of circadian rhythm disruption in aging is delineated.
  20. Vyas T, Rapalli VK, Chellappan DK, Dua K, Dubey SK, Singhvi G
    Life Sci, 2021 Dec 15;287:120148.
    PMID: 34785190 DOI: 10.1016/j.lfs.2021.120148
    BACKGROUND: Biofilms are microcolonies of microbes that form communities with a variety of microbes, exhibit the same gene composition but differ in gene expression. Biofilm-associated infections have been in existence for a long, however, biofilm-associated skin disorders have not been investigated much.

    OBJECTIVES: Biofilms, which are made mostly of the matrix can be thought of as communities of microbes that are more virulent and more difficult to eradicate as compared to their planktonic counterparts. Currently, several formulations are available in the market which have the potential to treat biofilm-assisted skin disorders. However, the existing pharmacotherapies are not competent enough to cure them effectively and entirely, in several cases.

    KEY FINDINGS: Especially with the rising resistance towards antibiotics, it has become particularly challenging to ameliorate these disorders completely. The new approaches are being used to combat biofilm-associated skin disorders, some of them being photodynamic therapy, nanotherapies, and the use of novel drug delivery systems. The focus of attention, however, is nanotherapy. Micelles, solid lipid nanoparticles, quatsomes, and many others are being considered to find a better solution for the biofilm-associated skin disorders.

    SIGNIFICANCE: This review is an attempt to give a perspective on these new approaches for treating bacterial biofilms associated with skin disorders.

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