Displaying publications 141 - 160 of 306 in total

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  1. Sah SK, Samuel VP, Dahiya S, Singh Y, Gilhotra RM, Gupta G, et al.
    Chem Biol Interact, 2019 Jun 01;306:117-122.
    PMID: 31004596 DOI: 10.1016/j.cbi.2019.04.022
    Major challenges of dealing elder patients with diabetes mellitus (DM) are the individualization of consideration in persons with various comorbid types of conditions. In spite of the fact that microvascular and macrovascular problems associated with DM are well documented, there is only a few numbers of reports viewing different conditions, for example, cognitive dysfunction. Cognitive dysfunction is of specific significance due to its effect on self-care and quality of life. All in all, the etiology of cognitive dysfunction in the maturing populace is probably going to be the grouping of ischemic and degenerative pathology. It is likewise trusted that Hyperglycemia is engaged with the system of DM-related cognitive dysfunction. At present, it isn't certain in the case of enhancing glycemic control or utilizing therapeutic agents can enhance the risk of cognitive decay. Amylin was later characterized as an amyloidogenic peptide, confined from a beta cell tumor and called islet amyloid polypeptide (IAPP), and after that, amylin. Conversely, we investigate the beneficial role and hypothesizing the mechanism of amylin related expanding the level and activation of CGRP receptor to enhance the cognition declination amid diabetic dementia.
  2. Mehta M, Deeksha, Tewari D, Gupta G, Awasthi R, Singh H, et al.
    Chem Biol Interact, 2019 Aug 01;308:206-215.
    PMID: 31136735 DOI: 10.1016/j.cbi.2019.05.028
    Oligonucleotide-based therapies are advanced novel interventions used in the management of various respiratory diseases such as asthma and Chronic Obstructive Pulmonary Disease (COPD). These agents primarily act by gene silencing or RNA interference. Better methodologies and techniques are the need of the hour that can deliver these agents to tissues and cells in a target specific manner by which their maximum potential can be reached in the management of chronic inflammatory diseases. Nanoparticles play an important role in the target-specific delivery of drugs. In addition, oligonucleotides also are extensively used for gene transfer in the form of polymeric, liposomal and inorganic carrier materials. Therefore, the current review focuses on various novel dosage forms like nanoparticles, liposomes that can be used efficiently for the delivery of various oligonucleotides such as siRNA and miRNA. We also discuss the future perspectives and targets for oligonucleotides in the management of respiratory diseases.
  3. Chan Y, Ng SW, Xin Tan JZ, Gupta G, Tambuwala MM, Bakshi HA, et al.
    Chem Biol Interact, 2019 Nov 28;315:108911.
    PMID: 31786185 DOI: 10.1016/j.cbi.2019.108911
    Over the years, the attention of researchers in the field of modern drug discovery and development has become further intense on the identification of active compounds from plant sources and traditional remedies, as they exhibit higher therapeutic efficacies and improved toxicological profiles. Among the large diversity of plant extracts that have been discovered and explored for their potential therapeutic benefits, asperuloside, an iridoid glycoside, has been proven to provide promising effects as a therapeutic agent for several diseases. Although, this potent substance exists in several genera, it is primarily found in plants belonging to the genus Eucommia. Recent decades have seen a surge in the research on Asperuloside, making it one of the most studied natural products in the field of medicine and pharmacology. In this review, we have attempted to study the various reported mechanisms of asperuloside that form the basis of its wide spectrum of pharmacological activities.
  4. Ramanunny AK, Wadhwa S, Gulati M, Singh SK, Kapoor B, Dureja H, et al.
    Eur J Pharmacol, 2021 Jan 05;890:173691.
    PMID: 33129787 DOI: 10.1016/j.ejphar.2020.173691
    Skin diseases are the fourth leading non-fatal skin conditions that act as a burden and affect the world economy globally. This condition affects the quality of a patient's life and has a pronounced impact on both their physical and mental state. Treatment of these skin conditions with conventional approaches shows a lack of efficacy, long treatment duration, recurrence of conditions, systemic side effects, etc., due to improper drug delivery. However, these pitfalls can be overcome with the applications of nanomedicine-based approaches that provide efficient site-specific drug delivery at the target site. These nanomedicine-based strategies are evolved as potential treatment opportunities in the form of nanocarriers such as polymeric and lipidic nanocarriers, nanoemulsions along with emerging others viz. carbon nanotubes for dermatological treatment. The current review focuses on challenges faced by the existing conventional treatments along with the topical therapeutic perspective of nanocarriers in treating various skin diseases. A total of 213 articles have been reviewed and the application of different nanocarriers in treating various skin diseases has been explained in detail through case studies of previously published research works. The toxicity related aspects of nanocarriers are also discussed.
  5. 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.
  6. Mehta M, Paudel KR, Shukla SD, Shastri MD, Satija S, Singh SK, et al.
    Future Med Chem, 2021 03;13(6):543-549.
    PMID: 33538615 DOI: 10.4155/fmc-2020-0297
    Aim: In the present study, the inhibitory potential of rutin-loaded liquid crystalline nanoparticles (LCNs) on oxidative stress was determined in human bronchial epithelial cells (BEAS-2B) by analysing the expression levels of different antioxidant (NADPH quinine oxidoreductase-1 (NQO1); γ-glutamyl cysteine synthetase catalytic subunit (GCLC)) and pro-oxidant (NADPH oxidase (Nox)-4; Nox2B) genes. Results: Our findings revealed that the rutin-loaded LCNs inhibited the genes, namely Nox2B and Nox4, which caused oxidative stress. In addition, these nanoparticles demonstrated an upregulation in the expression of the antioxidant genes Gclc and Nqo-1 in a dose-dependent manner. Conclusion: The study indicates the promising potential of rutin-loaded LCNs as an effective treatment strategy in patients with high oxidant loads in various respiratory diseases.
  7. Gulati N, Kumar Chellappan D, M Tambuwala M, A A Aljabali A, Prasher P, Kumar Singh S, et al.
    Assay Drug Dev Technol, 2021 05 14;19(4):246-261.
    PMID: 33989048 DOI: 10.1089/adt.2021.012
    Nanoemulsions (NMs) are one of the most important colloidal dispersion systems that are primarily used to improve the solubility of poorly water soluble drugs. The main objectives of this study were, first, to prepare an NM loaded with fenofibrate using a high shear homogenization technique and, second, to study the effect of variable using a central composite design. Twenty batches of fenofibrate-loaded NM formulations were prepared. The formed NMs were subjected to droplet size analysis, zeta potential, entrapment efficiency, pH, dilution, polydispersity index, transmission electron microscopy (TEM), Fourier transform infrared spectrophotometry, differential scanning calorimetry (DSC), and in vitro drug release study. Analysis of variance was used for entrapment efficiency data to study the fitness and significance of the design. The NM-7 batch formulation demonstrated maximum entrapment efficiency (81.82%) with lowest droplet size (72.28 nm), and was thus chosen as the optimized batch. TEM analysis revealed that the NM was well dispersed with droplet sizes <100 nm. Incorporation of the drug into the NM was confirmed with DSC studies. In addition, the batch NM-7 also showed the maximum in vitro drug release (87.6%) in a 0.05 M sodium lauryl sulfate solution. The release data revealed that the NM followed first-order kinetics. The outcomes of the study revealed the development of a stable oral NM containing fenofibrate using the high shear homogenization technique. This approach may aid in further enhancing the oral bioavailability of fenofibrate, which requires further in vivo studies.
  8. Khursheed R, Singh SK, Wadhwa S, Gulati M, Kapoor B, Awasthi A, et al.
    Expert Opin Drug Deliv, 2021 04;18(4):427-448.
    PMID: 33356647 DOI: 10.1080/17425247.2021.1846517
    Introduction: Diabetic neuropathy (DN) is one of the major complications arising from hyperglycaemia in diabetic patients. In recent years polyphenols present in plants have gained attention to treat DN. The main advantages associated with them are their action via different molecular pathways to manage DN and their safety. However, they failed to gain clinical attention due to challenges associated with their formulation development such as lipophilicity,poor bioavailability, rapid systemic elimination, and enzymatic degradation.Area covered: This article includes different polyphenols that have shown their potential against DN in preclinical studies and the research carried out towards development of their nanoformulations in order to overcome aforementioned issues.Expert opinion: In this review various polyphenol based nanoformulations such as nanospheres, self-nanoemulsifying drug delivery systems, niosomes, electrospun nanofibers, metallic nanoparticles explored exclusively to treat DN are discussed. However, the literature available related to polyphenol based nanoformulations to treat DN is limited. Moreover, these experiments are limited to preclinical studies. Hence, more focus is required towards  development of nanoformulations using simple and single step process as well as inexpensive and non-toxic excipients so that a stable, scalable, reproducible and non-toxic formulation could be achieved and clinical trials could be initiated.
  9. Gupta G, Singh Y, Tiwari J, Raizaday A, Alharbi KS, Al-Abbasi FA, et al.
    Dermatol Ther, 2020 11;33(6):e14209.
    PMID: 32816372 DOI: 10.1111/dth.14209
    Psoriasis is a chronic, local as well as a systemic, inflammatory skin condition. Psoriasis influences the quality of life up to 3.8% of the population and occurs often between 15 and 30 years of age. Specific causes are linked to psoriasis, including the interleukin IL-23/IL-17 Axis, human antigen leucocyte (HLA), and tumor necrosis factor-α (TNF-α). Secukinumab is a monoclonal antibody that specifically binds and neutralizes IL-17A required in the treatment of Psoriasis. The signaling pathways of Wnt govern multiple functions of cell-like fate specification, proliferation, polarity, migration, differentiation with their signaling controlled rigorously, given that dysregulation caused by various stimuli, can lead to alterations in cell proliferation, apoptosis, and human inflammatory disease. Current data has supported non-canonical Wnt signaling pathways in psoriasis development, particularly Wnt5a activated signaling cascades. These interconnected factors are significant in interactions between immune cells, keratinocytes, and inflammatory factors due to a higher degree of transglutaminase 2, mediated by activation of the keratinocyte hyperproliferation of the psoriatic patient's epidermis. This study discusses the pathology of Wnt5a signaling and its involvement in the epidermal inflammatory effects of psoriasis with other related pathways.
  10. 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.
  11. Chan Y, Mehta M, Paudel KR, Madheswaran T, Panneerselvam J, Gupta G, et al.
    Nanomedicine (Lond), 2021 08;16(18):1545-1548.
    PMID: 34184917 DOI: 10.2217/nnm-2021-0114
  12. Solanki N, Mehta M, Chellappan DK, Gupta G, Hansbro NG, Tambuwala MM, et al.
    Future Med Chem, 2020 11;12(22):2019-2034.
    PMID: 33124483 DOI: 10.4155/fmc-2020-0083
    Aim: In the present study boswellic acids-loaded chitosan nanoparticles were synthesized using ionic gelation technique. The influence of independent variables were studied and optimized on dependent variables using central composite design. Methodology & results: The designed nanoparticles were observed spherical in shape with an average size of 67.5-187.2 nm and have also shown an excellent entrapment efficiency (80.06 ± 0.48). The cytotoxicity assay revealed enhanced cytotoxicity for drug-loaded nanoparticles in contrast to the free drug having an IC50 value of 17.29 and 29.59 μM, respectively. Flow cytometry confirmed that treatment of cells with 40 μg/ml had arrested 22.75 ± 0.3% at SubG0 phase of the cell cycle when compared with untreated A459 cells. The observed results justified the boswellic acids-loaded chitosan nanoparticles were effective due to greater cellular uptake, sustained intercellular drug retention and enhanced antiproliferative effect by inducing apoptosis.
  13. Chan Y, MacLoughlin R, Zacconi FC, Tambuwala MM, Pabari RM, Singh SK, et al.
    Nanomedicine (Lond), 2021 07;16(16):1351-1355.
    PMID: 33998829 DOI: 10.2217/nnm-2021-0087
  14. Kaur J, Mishra V, Singh SK, Gulati M, Kapoor B, Chellappan DK, et al.
    J Control Release, 2021 06 10;334:64-95.
    PMID: 33887283 DOI: 10.1016/j.jconrel.2021.04.014
    Amphiphilic block copolymers are widely utilized in the design of formulations owing to their unique physicochemical properties, flexible structures and functional chemistry. Amphiphilic polymeric micelles (APMs) formed from such copolymers have gained attention of the drug delivery scientists in past few decades for enhancing the bioavailability of lipophilic drugs, molecular targeting, sustained release, stimuli-responsive properties, enhanced therapeutic efficacy and reducing drug associated toxicity. Their properties including ease of surface modification, high surface area, small size, and enhanced permeation as well as retention (EPR) effect are mainly responsible for their utilization in the diagnosis and therapy of various diseases. However, some of the challenges associated with their use are premature drug release, low drug loading capacity, scale-up issues and their poor stability that need to be addressed for their wider clinical utility and commercialization. This review describes comprehensively their physicochemical properties, various methods of preparation, limitations followed by approaches employed for the development of optimized APMs, the impact of each preparation technique on the physicochemical properties of the resulting APMs as well as various biomedical applications of APMs. Based on the current scenario of their use in treatment and diagnosis of diseases, the directions in which future studies need to be carried out to explore their full potential are also discussed.
  15. Singh Y, Ali H, Alharbi KS, Almalki WH, Kazmi I, Al-Abbasi FA, et al.
    Drug Dev Res, 2021 09;82(6):784-788.
    PMID: 33687087 DOI: 10.1002/ddr.21810
    Over the recent decades, a number of new pathogens have emerged within specific and diverse populations across the globe, namely, the Nipah virus, the Ebola virus, the Zika virus, and coronaviruses (CoVs) to name a few. Recently, a new form of coronavirus was identified in the city of Wuhan, China. Interestingly, the genomic architecture of the virus did not match with any of the existing genomic sequencing data of previously sequenced CoVs. This had led scientists to confirm the emergence of a new CoV strain. Originally, named as 2019-nCoV, the strain is now called as SARS-CoV-2. High serum levels of proinflammatory mediators, namely, interleukin-12 (IL-12), IL-1β, IL-6, interferon-gamma (IFNγ), chemoattractant protein-1, and IFN-inducible protein, have been repeatedly observed in subjects who were infected with this virus. In addition, the virus demonstrated strong coagulation activation properties, leading to further the understanding on the SARS-CoV2. To our understanding, these findings are unique to the published literature. Numerous studies have reported anomalies, namely, decline in the number of lymphocytes, platelets and albumins; and a rise in neutrophil count, aspartate transaminase, alanine aminotransaminase, lactate dehydrogenase, troponins, creatinine, complete bilirubin, D-dimers, and procalcitonin. Supplementation of calcium during the SARS CoV-2 associated hyperactive stage of calcium-sensing receptors (CaSR) may be harmful to the cardio-renal system. Thus, pharmacological inhibition of CaSR may prevent the increase in the levels of intracellular calcium, oxidative, inflammatory stress, and cardio-renal cellular apoptosis induced by high cytokines level in COVID-19 infection.
  16. 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.
  17. Palaniveloo K, Yee-Yinn L, Jia-Qi L, Chelliah A, Sze-Looi S, Nagappan T, et al.
    Foods, 2021 Aug 20;10(8).
    PMID: 34441709 DOI: 10.3390/foods10081932
    Seaweeds are an important ingredient of functional foods recommended for daily food, due to their unique compositions and nutritional value. Padina tetrastromatica is a brown edible seaweed that is commonly found along the coastal regions of Peninsular Malaysia and consumed as food by some coastal communities. This study investigates the nutritional and antihyperglycaemic potential of P. tetrastromatica extracts, which is generally accepted as an important functional food. In our methodology, we induced diabetes intraperitoneally in experimental animals with a dose of 65 mg kg-1 body weight of streptozotocin. Oral treatment with 200 and 400 mg kg-1 of P. tetrastromatica ethanolic and ethyl acetate extracts were initiated, respectively, to experimental rats once daily for 18 days. Metformin was used as the positive control. Biochemical estimations and histopathological analysis were included in this study. Treatment with P. tetrastromatica extracts significantly lowered the plasma glucose levels in Streptozotocin-induced diabetic rats. In addition, P. tetrastromatica extract treatment also showed a significant reduction in serum alanine transaminase levels. However, no significant changes were observed in serum aspartate transaminase levels. The ethyl acetate extract of P. tetrastromatica at 400 mg kg-1 dose shows some nephroprotective effect, which is observed from the significant increase in the plasma albumin levels. Histopathological evaluation revealed no marked morphological changes in tissues of the isolated organs of the ethyl acetate extract-treated group, revealing the safe nature of P. tetrastromatica.
  18. Aggarwal T, Wadhwa R, Gupta R, Paudel KR, Collet T, Chellappan DK, et al.
    PMID: 32342824 DOI: 10.2174/1871530320666200428113051
    Regardless of advances in detection and treatment, breast cancer affects about 1.5 million women all over the world. Since the last decade, genome-wide association studies (GWAS) have been extensively conducted for breast cancer to define the role of miRNA as a tool for diagnosis, prognosis and therapeutics. MicroRNAs are small, non-coding RNAs that are associated with the regulation of key cellular processes such as cell multiplication, differentiation, and death. They cause a disturbance in the cell physiology by interfering directly with the translation and stability of a targeted gene transcript. MicroRNAs (miRNAs) constitute a large family of non-coding RNAs, which regulate target gene expression and protein levels that affect several human diseases and are suggested as the novel markers or therapeutic targets, including breast cancer. MicroRNA (miRNA) alterations are not only associated with metastasis, tumor genesis but also used as biomarkers for breast cancer diagnosis or prognosis. These are explained in detail in the following review. This review will also provide an impetus to study the role of microRNAs in breast cancer.
  19. Chellappan DK, Leng KH, Jia LJ, Aziz NABA, Hoong WC, Qian YC, et al.
    Biomed Pharmacother, 2018 Jun;102:1127-1144.
    PMID: 29710531 DOI: 10.1016/j.biopha.2018.03.061
    OBJECTIVE: The study aims to analyze the effectiveness of bevacizumab in addressing the complications associated with gynecological cancers and evaluates effective treatments for various gynecological cancers.

    METHODS: The study follows a systematic review approach that has been implemented to analyze the qualitative published data from previous studies. Studies related with the trials of angiogenesis and bevacizumab were selected in the review.

    RESULTS: In general, the management of gynecological cancers include chemotherapy, surgery and radiation therapy. Results suggest bevacizumab as an effective treatment modality for cervical and several other cancers. Overall, bevacizumab showed promising results in improving the overall survival rate of gynecological cancer patients through the combination of bevacizumab with other chemotherapeutic agents.

    CONCLUSION: Bevacizumab possess less documented adverse effects when compared to other chemotherapeutic agents. The manifestation and severity of adverse effects reported varied according to the chemotherapeutic agent(s) that were used with bevacizumab in combination therapy. Overall, bevacizumab effectively improved the survival rate in patients with several gynaecological cancers.

  20. Ng ZY, Wong JY, Panneerselvam J, Madheswaran T, Kumar P, Pillay V, et al.
    Colloids Surf B Biointerfaces, 2018 Dec 01;172:51-59.
    PMID: 30134219 DOI: 10.1016/j.colsurfb.2018.08.027
    Curcumin a component of turmeric, which is derived from Curcuma longa is used as a colouring agent and as a dietary spice for centuries. Extensive studies have been done on the anti-inflammatory activity of curcumin along with its molecular mechanism involving different signalling pathways. However, the physicochemical and biological properties such as poor solubility and rapid metabolism of curcumin have led to low bioavailability and hence limits its application. Current therapies for asthma such as bronchodilators and inhaled corticosteroids (ICS) are aimed at controlling disease symptoms and prevent asthma exacerbation. However, this approach requires lifetime therapy and is associated with a constellation of side effects. This creates a clear unmet medical need and there is an urgent demand for new and more-effective treatments. The present study is aimed to formulate liposomes containing curcumin and evaluate for its anti-inflammatory effects on lipopolysaccharide (LPS)-induced inflammation on BCi-NS1.1 cell line. Curcumin and salbutamol liposomes were formulated using lipid hydration method. The prepared liposomes were characterized in terms of particle size, zeta potential, encapsulation efficiency and in-vitro release profile. The liposomes were tested on BCI-NS1.1 cell line to evaluate its anti-inflammatory properties. The various pro-inflammatory markers studied were Interleukin-6 (IL-6), Interleukin-8 (IL-8), Interleukin-1β (IL-1β) and Tumour Necrosis Factor-a (TNF-a). Additionally, molecular mechanics simulations were used to elucidate the positioning, energy minimization, and aqueous dispersion of the liposomal architecture involving lecithin and curcumin. The prepared curcumin formulation showed an average size and zeta potential of 271.3 ± 3.06 nm and -61.0 mV, respectively. The drug encapsulation efficiency of liposomal curcumin is 81.1%. Both curcumin-loaded liposomes formulation (1 μg/mL, 5 μg/mL) resulted in significant (p 
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