Displaying publications 41 - 60 of 225 in total

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  1. Gupta G, de Jesus Andreoli Pinto T, Chellappan DK, Mishra A, Malipeddi H, Dua K
    Panminerva Med, 2018 Jun;60(2):70-75.
    PMID: 29370676 DOI: 10.23736/S0031-0808.18.03394-3
    Diabetes mellitus (DM) is frequently increased in many countries and become a serious health problem worldwide. Diabetes is associated with dysfunction of different organs such as heart, eyes, blood vessels, nerves, and kidneys. There is a strong connection between diabetes and cancer. Metformin is one of the most commonly prescribed oral antidiabetic medicines and it is suggested as the first-line therapy due to its comparatively safe, inexpensive, effective and well-tolerated. Some of the in vitro and in vivo investigations proved that metformin may have a direct anticancer action by preventing the proliferation of malignant cells and formations of the colony, inducing arrest of cell cycle and apoptosis and suppressing tumor growth. The antiproliferative mechanism of metformin alone or in combination with various chemotherapeutic agents is complex and involves several beneficial roles. In this regard, clinical studies are required to explain these roles. In the coming future, the use of metformin, alone or in combination with current chemotherapy, might be a conventional approach to effectually manage lung cancer. This mini-review provides a critical overview of currently available clinical trials investigating the effects of metformin in lung cancer.
  2. 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.
  3. Bhatt S, Kanoujia J, Mohana Lakshmi S, Patil CR, Gupta G, Chellappan DK, et al.
    CNS Neurol Disord Drug Targets, 2023;22(2):276-288.
    PMID: 35352640 DOI: 10.2174/1871527321666220329140804
    The human gut microbiota plays a significant role in the pathophysiology of central nervous system-related diseases. Recent studies suggest correlations between the altered gut microbiota and major depressive disorder (MDD). It is proposed that normalization of the gut microbiota alleviates MDD. The imbalance of brain-gut-microbiota axis also results in dysregulation of the hypothalamicpituitary- adrenal (HPA) axis. This imbalance has a crucial role in the pathogenesis of depression. Treatment strategies with certain antibiotics lead to the depletion of useful microbes and thereby induce depression like effects in subjects. Microbiota is also involved in the synthesis of various neurotransmitters (NTs) like 5-hydroxy tryptamine (5-HT; serotonin), norepinephrine (NE) and dopamine (DA). In addition to NTs, the gut microbiota also has an influence on brain derived neurotrophic factor (BDNF) levels. Recent research findings have exhibited that transfer of stress prone microbiota in mice is also responsible for depression and anxiety-like behaviour in animals. The use of probiotics, prebiotics, synbiotics and proper diet have shown beneficial effects in the regulation of depression pathogenesis. Moreover, transplantation of fecal microbiota from depressed individuals to normal subjects also induces depression-like symptoms. With the precedence of limited therapeutic benefits from monoamine targeting drugs, the regulation of brain-gut microbiota is emerging as a new treatment modality for MDDs. In this review, we elaborate on the significance of brain-gut-microbiota axis in the progression of MDD, particularly focusing on the modulation of the gut microbiota as a mode of treating MDD.
  4. Gulati N, Chellappan DK, MacLoughlin R, Gupta G, Singh SK, Oliver BG, et al.
    PMID: 38078921 DOI: 10.1007/s00210-023-02882-y
    Asthma, lung cancer, cystic fibrosis, tuberculosis, acute respiratory distress syndrome, chronic obstructive pulmonary disease, and COVID-19 are few examples of inflammatory lung conditions that cause cytokine release syndrome. It can initiate a widespread inflammatory response and may activate several inflammatory pathways that cause multiple organ failures leading to increased number of deaths and increased prevalence rates around the world. Nanotechnology-based therapeutic modalities such as nanoparticles, liposomes, nanosuspension, monoclonal antibodies, and vaccines can be used in the effective treatment of inflammatory lung diseases at both cellular and molecular levels. This would also help significantly in the reduction of patient mortality. Therefore, nanotechnology could be a potent platform for repurposing current medications in the treatment of inflammatory lung diseases. The aim and approach of this article are to highlight the clinical manifestations of cytokine storm in inflammatory lung diseases along with the advances and potential applications of nanotechnology-based therapeutics in the management of cytokine storm. Further in-depth studies are required to understand the molecular pathophysiology, and how nanotechnology-based therapeutics can help to effectively combat this problem.
  5. Malhotra S, Jain N, Rathee J, Kaul S, Nagaich U, Pandey M, et al.
    Recent Pat Nanotechnol, 2024;18(2):256-271.
    PMID: 38197418 DOI: 10.2174/1872210517666230403105152
    Neurological disorders (ND) have affected a major part of our society and have been a challenge for medical and biosciences for decades. However, many of these disorders haven't responded well to currently established treatment approaches. The fact that many active pharmaceutical ingredients can't get to their specified action site inside the body is one of the main reasons for this failure. Extracellular and intracellular central nervous system (CNS) barriers prevent the transfer of drugs from the blood circulation to the intended location of the action. Utilizing nanosized drug delivery technologies is one possible way to overcome these obstacles. These nano-drug carriers outperform conventional dosage forms in many areas, including good drug encapsulation capacity, targeted drug delivery, less toxicity, and enhanced therapeutic impact. As a result, nano-neuroscience is growing to be an intriguing area of research and a bright alternative approach for delivering medicines to their intended action site for treating different neurological and psychiatric problems. In this review, we have included a short overview of the pathophysiology of neurological diseases, a detailed discussion about the significance of nanocarriers in NDs, and a focus on its recent advances. Finally, we highlighted the patented technologies and market trends, including the predictive analysis for the years 2021-2028.
  6. Lokesh, Gulati N, Saini A, Singh S, Gupta G, MacLoughlin R, et al.
    Curr Drug Deliv, 2024 Mar 05.
    PMID: 38445696 DOI: 10.2174/0115672018289883240226113353
    Chronic Obstructive Pulmonary Disease (COPD), a chronic lung disease that causes breathing difficulties and obstructs airflow from the lungs, has a significant global health burden and affects millions of people worldwide. The use of pharmaceuticals in COPD treatment is aimed to alleviate symptoms, improve lung function, prevent exacerbations, and enhance the overall quality of life for patients. Nanotechnology holds great promise to alleviate the burden of COPD. The main goal of this review is to present the full spectrum of therapeutics based on nanostructures for the treatment and management of COPD, including nanoparticles, polymeric nanoparticles, polymeric micelles, solid-lipid nanoparticles, liposomes, exosomes, nanoemulsions, nanosuspensions, and niosomes. Nanotechnology is just one of the many areas of research that may contribute to the development of more effective and personalized treatment modalities for COPD patients in the future. Future studies may be focused on enhancing the therapeutic effectiveness of nanocarriers by conducting extensive mechanistic investigations to translate current scientific knowledge for the effective management of COPD with little or no adverse effects.
  7. Acharya M, Singh N, Gupta G, Tambuwala MM, Aljabali AAA, Chellappan DK, et al.
    Cell Signal, 2024 Apr;116:111043.
    PMID: 38211841 DOI: 10.1016/j.cellsig.2024.111043
    Calcium is a ubiquitous second messenger that is indispensable in regulating neurotransmission and memory formation. A precise intracellular calcium level is achieved through the concerted action of calcium channels, and calcium exerts its effect by binding to an array of calcium-binding proteins, including calmodulin (CAM), calcium-calmodulin complex-dependent protein kinase-II (CAMK-II), calbindin (CAL), and calcineurin (CAN). Calbindin orchestrates a plethora of signaling events that regulate synaptic transmission and depolarizing signals. Vitamin D, an endogenous fat-soluble metabolite, is synthesized in the skin upon exposure to ultraviolet B radiation. It modulates calcium signaling by increasing the expression of the calcium-sensing receptor (CaSR), stimulating phospholipase C activity, and regulating the expression of calcium channels such as TRPV6. Vitamin D also modulates the activity of calcium-binding proteins, including CAM and calbindin, and increases their expression. Calbindin, a high-affinity calcium-binding protein, is involved in calcium buffering and transport in neurons. It has been shown to inhibit apoptosis and caspase-3 activity stimulated by presenilin 1 and 2 in AD. Whereas CAM, another calcium-binding protein, is implicated in regulating neurotransmitter release and memory formation by phosphorylating CAN, CAMK-II, and other calcium-regulated proteins. CAMK-II and CAN regulate actin-induced spine shape changes, which are further modulated by CAM. Low levels of both calbindin and vitamin D are attributed to the pathology of Alzheimer's disease. Further research on vitamin D via calbindin-CAMK-II signaling may provide newer insights, revealing novel therapeutic targets and strategies for treatment.
  8. 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.
  9. 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
  10. Gupta G, Singhvi G, Chellappan DK, Sharma S, Mishra A, Dahiya R, et al.
    Panminerva Med, 2018 Sep;60(3):109-116.
    PMID: 30176701 DOI: 10.23736/S0031-0808.18.03462-6
    Glioblastoma, also known as glioblastoma multiforme, is the most common and worldwide-spread cancer that begins within the brain. Glioblastomas represent 15% of brain tumors. The most common length of survival following diagnosis is 12 to 14 months with less than 3% to 5% of people surviving longer than five years. Without treatment, survival is typically 3 months. Among all receptors, special attention has been focused on the role of peroxisome proliferator-activated receptors (PPARs) in glioblastoma. PPARs are ligand-activated intracellular transcription factors. The PPAR subfamily consists of three subtypes encoded by distinct genes named PPARα, PPARβ/δ, and PPARγ. PPARγ is the most extensively studied subtype of PPAR. There has been interesting preliminary evidence suggesting that diabetic patients receiving PPARγ agonists, a group of anti-diabetics, thiazolidinedione drugs, have an increased median survival for glioblastoma. In this paper, the recent progresses in understanding the potential mechanism of PPARγ in glioblastoma are summarized.
  11. Rathore C, Rathbone MJ, Chellappan DK, Tambuwala MM, Pinto TJA, Dureja H, et al.
    Expert Opin Drug Deliv, 2020 04;17(4):479-494.
    PMID: 32077770 DOI: 10.1080/17425247.2020.1730808
    Introduction: Thymoquinone (TQ), 2-isopropyl-5-methylbenzo-1, 4-quinone, the main active constituent of Nigella sativa (NS) plant, has been proven to be of great therapeutic aid in various in vitro and in vivo conditions. Despite the promising therapeutic activities of TQ, this molecule is not yet in the clinical trials, restricted by its poor biopharmaceutical properties including photo-instability.Area covered: This review compiles the different types of polymeric and lipidic nanocarriers (NCs), encapsulating TQ for their improved oral bioavailability, and augmented in vitro and in vivo efficacy, evidenced on various pathologies. Furthermore, we provide a comprehensive overview of TQ in relation to its encapsulation approaches advancing the delivery and improving the efficacy of TQ.Expert opinion: TQ was first identified in the essential oil of Nigella sativa L. black seed. TQ has not been used in formulations because it is a highly hydrophobic drug having poor aqueous solubility. To deal with the poor physicochemical problems associated with TQ, various NCs encapsulating TQ have been tried in the past. Nevertheless, these NCs could be impending in bringing forth this potential molecule to clinical reality. This will also be beneficial for a large research community including pharmaceutical & biological sciences and translational researchers.
  12. Rajeshkumar S, Menon S, Venkat Kumar S, Tambuwala MM, Bakshi HA, Mehta M, et al.
    J. Photochem. Photobiol. B, Biol., 2019 Aug;197:111531.
    PMID: 31212244 DOI: 10.1016/j.jphotobiol.2019.111531
    Environment friendly methods for the synthesis of copper nanoparticles have become a valuable trend in the current scenario. The utilization of phytochemicals from plant extracts has become a unique technology for the synthesis of nanoparticles, as they possess dual nature of reducing and capping agents to the nanoparticles. In the present investigation we have synthesized copper nanoparticles (CuNPs) using a rare medicinal plant Cissus arnotiana and evaluated their antibacterial activity against gram negative and gram positive bacteria. The morphology and characterization of the synthesized CuNPs were studied and done using UV-Visible spectroscopy at a wavelength range of 350-380 nm. XRD studies were performed for analyzing the crystalline nature; SEM and TEM for evaluating the spherical shape within the size range of 60-90 nm and AFM was performed to check the surface roughness. The biosynthesized CuNPs showed better antibacterial activity against the gram-negative bacteria, E. coli with an inhibition zone of 22.20 ± 0.16 mm at 75 μg/ml. The antioxidant property observed was comparatively equal with the standard antioxidant agent ascorbic acid at a maximum concentration of 40 μg/ ml. This is the first study reported on C. arnotiana mediated biosynthesis of copper nanoparticles, where we believe that the findings can pave way for a new direction in the field of nanotechnology and nanomedicine where there is a significant potential for antibacterial and antioxidant activities. We predict that, these could lead to an exponential increase in the field of biomedical applications, with the utilization of green synthesized CuNPs, due to its remarkable properties. The highest antibacterial property was observed with gram-negative strains mainly, E. coli, due to its thin peptidoglycan layer and electrostatic interactions between the bacterial cell wall and CuNPs surfaces. Hence, CuNPs can be potent therapeutic agents in several biomedical applications, which are yet to be explored in the near future.
  13. 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
  14. Yap PK, Loo Xin GL, Tan YY, Chellian J, Gupta G, Liew YK, et al.
    J Pharm Pharmacol, 2019 Sep;71(9):1339-1352.
    PMID: 31144296 DOI: 10.1111/jphp.13107
    OBJECTIVES: Antiretroviral agents (ARVs) have been the most promising line of therapy in the management of human immunodeficiency virus (HIV) infections. Some of these ARVs are used in the pre-exposure prophylaxis (PrEP) to suppress the transmission of HIV. Prophylaxis is primarily used in uninfected people, before exposure, to effectively prevent HIV infection. Several studies have shown that ART PrEP prevents HIV acquisition from sexual, blood and mother-to-child transmissions. However, there are also several challenges and limitations to PrEP. This review focuses on the current antiretroviral therapies used in PrEP.

    KEY FINDINGS: Among ARVs, the most common drugs employed from the class of entry inhibitors are maraviroc (MVC), which is a CCR5 receptor antagonist. Other entry inhibitors like emtricitabine (FTC) and tenofovir (TFV) are also used. Rilpivirine (RPV) and dapivirine (DPV) are the most common drugs employed from the Non-nucleoside reverse transcriptase inhibitor (NNRTIs) class, whereas, tenofovir disoproxil fumarate (TDF) is primarily used in the Nucleoside Reverse Transcriptase Inhibitor (NRTIs) class. Cabotegravir (CAB) is an analog of dolutegravir, and it is an integrase inhibitor. Some of these drugs are also used in combination with other drugs from the same class.

    SUMMARY: Some of the most common pre-exposure prophylactic strategies employed currently are the use of inhibitors, namely entry inhibitors, non-nucleoside reverse transcriptase inhibitors, nucleoside reverse transcriptase inhibitors, integrase and protease inhibitors. In addition, we have also discussed on the adverse effects caused by ART in PrEP, pharmacoeconomics factors and the use of antiretroviral prophylaxis in serodiscordant couples.

  15. Kaur J, Gulati M, Gowthamarajan K, Vishwas S, Kumar Chellappan D, Gupta G, et al.
    Med Hypotheses, 2021 Sep 14;156:110679.
    PMID: 34555619 DOI: 10.1016/j.mehy.2021.110679
    Colon cancer is characterised by the persistent change in bowel habits due to the formation of polyps (cancerous) in the inner lining of the colon. Clinically, there are several anticancer drugs available to treat colon cancer. Oxaliplatin (third generation platinum drug) is widely prescribed anticancer drug due to its broad range anticancer properties and low toxicities over cisplatin and carboplatin. Currently, use of oxaliplatin as adjuvant chemotherapy represents a standard care for the treatment of advanced colon cancer. Despite this, its rapid degradation in systemic circulations upon administration, lack of tumor specificity, and low bioavailability limits its anticancer potential. On the other hand, vanillic acid (VA) has shown anticancer potential in colon cancer by targeting mTOR/Ras pathway, HIF-1α inhibition, NF-ĸB, and Nrf2 that regulate cell growth, cell survival, proliferation and adaptation to cancer microenvironment. Normal oral delivery of these two drugs offers non-specific drug release in gastrointestinal tract that leads to unwanted toxicity and very less amount of drug become available for colonic site. Therefore, loading of these two drugs in polysaccharide based functionalized polymeric micelles (FPMs) can offer selective targeting at colonic site and could offer better therapeutic efficacy at much lesser doses of drugs. Therefore, a new hypothesis has been proposed that the combination of vanillic acid with oxaliplatin co-loaded in FPMs could provide colon targeting ability with enhanced potency and safety profile by targeting multiple pathways than current adjuvant chemotherapies available in the market for the treatment of colon cancer.
  16. Kazmi I, Alharbi KS, Al-Abbasi FA, Almalki WH, G SK, Yasmeen A, et al.
    Crit Rev Eukaryot Gene Expr, 2021;31(2):89-95.
    PMID: 34347983 DOI: 10.1615/CritRevEukaryotGeneExpr.2021037996
    Among various epithelial-to-mesenchymal transition (EMT)-related transcription factors (TFs), altered expression levels of Snail-1, Snail-2/Slug, Twist, and ZEB1 have shown a significant association in different cancers having a higher risk of metastasis. However, their role in the circulation of endometriosis patients is not well understood. Hence, the present study was designed to evaluate the crucial role of these TFs in defining the molecular pathogenesis for endometriosis progression and differentiation from control subjects. The qualitative and quantitative expression analysis of Snail-1, Snail-2/Slug, Twist, and ZEB1 were analyzed in peripheral blood samples of 75 different stages of endometriosis patients and compared with 50 control subjects. Total RNA was extracted and converted into complementary DNA (cDNA) for relative quantification of each gene transcript using SYBRGreen-based reverse transcriptase quantitative polymerase chain reaction (RT-qPCR). The Livak method of relative quantification was used for calculating the fold change in each TF compared with endogenous control. All four selected TFs showed significantly upregulated expression levels in endometriosis patients compared with control subjects. A three-fold increase was observed for Snail-1 (p = 0.0001), and a two-fold increase was observed for Snail-2 (p = 0.01), Twist (p = 0.0002), and ZEB1 (p = 0.001) in stage III and IV compared with stage I and II of endometriosis patients. The present study revealed that EMT-related TFs play a crucial role in the pathogenesis and differentiating different stages of endometriosis patients through expression analysis of specific molecular cascades using non-invasive tools.
  17. Gupta G, Chellappan DK, Kikuchi IS, Pinto TJA, Pabreja K, Agrawal M, et al.
    J Environ Pathol Toxicol Oncol, 2017;36(2):113-119.
    PMID: 29199592 DOI: 10.1615/JEnvironPatholToxicolOncol.2017019457
    Paracetamol (PCM) has an acceptable safety profile when used at prescribed doses. However, it is now understood that paracetamol can damage the kidneys when administered as an overdose. In addition, oxidative stress can play a major role in causing nephrotoxicity. This investigation studies the efficacy of moralbosteroid isolated from M. alba stem bark. Nephrotoxicity was induced with administration of paracetamol. Nephroprotection was studied using two doses of the extract. The experimental animals were divided into four groups (n = 6). Two groups served as positive and negative controls, respectively, and two received the test substances. All of the contents were orally administered. Significant reductions in nephrotoxicity and oxidative damages were observed in the treatment groups. There was a marked decrease in blood levels of urea, creatinine, and lipid peroxidation. Furthermore, it was found that glutathione levels in the blood increased dramatically after treatment. Histological findings confirmed the potent renoprotective potential of moralbosteroid. This was evidenced by the minimized intensity of nephritic cellular destruction. In animal studies, moralbosteroid exhibited dose-dependent activity, which is thought to be mediated through its antioxidant potential.
  18. Velu V, Banerjee S, Radhakrishnan V, Gupta G, Chellappan DK, Fuloria NK, et al.
    PMID: 33573582 DOI: 10.2174/1871523020666210126144506
    AIMS: The present investigation was aimed at exploring the phytoconstituents using Gas Chromatography Mass Spectroscopy and to evaluate antioxidant and anti-inflammatory properties of the leaf extracts.

    MATERIALS AND METHODS: The extracts were obtained sequentially with petroleum ether, ethyl acetate and water using Soxhlet apparatus. The anti-inflammatory property of the identified compounds using GC- MS spectroscopy was evaluated in silico. The antioxidant activity was performed by DPPH and H2O2 method whereas anti-inflammatory study was carried out by HRBC membrane stabilization method. Terpenoids were found to be a major constituents in petroleum ether extract while, phenols and flavonoids were predominantly found in ethyl acetate extract.

    RESULTS AND DISCUSSION: The GC-MS analysis of the extract revealed six major molecules including Squalene, 19β, 28-epoxyleanan-3-ol and 2-tu-Butyl-5-chloromethyl-3-methyl-4-oxoimidazolidine- 1-carboxylic acid. The ethyl acetate extract showed a significant antioxidant activity (P<0.01) in both DPPH method (70.87%) and H2O2 method (73.58%) at 200 μg mL-1. Increased membrane stabilization of petroleum ether extract was observed in the in vitro anti-inflammatory activity study. A strong relationship between the terpenoid content and anti-inflammatory activity was obtained from the correlation (0.971) and docking study.

    CONCLUSION: These results justify T. involucrata to be a rich source of terpenoids with potent anti- inflammatory property.

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