Displaying publications 521 - 540 of 1094 in total

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  1. Leptin-induced increase in blood pressure and markers of endothelial activation during pregnancy in Sprague Dawley rats is prevented by resibufogenin, a marinobufagenin antagonist
    Hassan MJM, Bakar NS, Aziz MA, Basah NK, Singh HJ
    Reprod Biol, 2020 Jun;20(2):184-190.
    PMID: 32253169 DOI: 10.1016/j.repbio.2020.03.004
    Levels of leptin and marinobufagenin (MBG), a cardiotonic steroid, are elevated in the serum of women with pre-eclampsia. Besides this, leptin administration to pregnant rats increases systolic blood pressure (SBP), urinary protein excretion and serum markers of endothelial activation. The link between leptin and MBG is unknown and it is also unclear if leptin-induced increases in blood pressure and proteinuria in the pregnant rat could be prevented by an MBG antagonist. To ascertain this link, this study investigated the effect of resibufogenin (RBG), a marinobufagenin antagonist, on leptin-induced increases in blood pressure and proteinuria during pregnancy in rats. Four groups of Sprague-Dawley rats, aged 12 weeks, were given either normal saline (CONTROL) or 120 μg/kg/day of leptin (LEP), or 120 μg/kg/day of leptin+30 μg/kg/day of resibufogenin (L + RBG) or 30 μg/kg/day of resibufogenin (RBG) from Day 1-20 of pregnancy. Systolic blood pressure and urinary protein excretion (UPE) were measured during the study period. Animals were euthanized on day 21 of pregnancy and vascular cell adhesion molecule 1, (VCAM-1), soluble intracellular cell adhesion molecule 1 (sICAM-1), E-selectin and endothelin-1 (ET-1) were estimated in the serum. SBP, UPE, VCAM-1, sICAM-1 and ET-1 were significantly higher only in the LEP group when compared with those in CONT and in L + RBG and RBG groups. The prevention by RBG of leptin-induced increases in SBP, proteinuria, and endothelial activation during pregnancy seem to suggest a potential role for MBG in leptin-induced adverse effects on blood pressure, urinary protein excretion and endothelial activity during pregnancy in the rat.
  2. Fulltext Emerging prospects of vitamin D3 in metabolic syndrome: A proof of concept (POC) approach targeting inflammation
    Singh Y, Gupta G, Gilhotra RM, Singh SK, Prasher P, Krishnan A, et al.
    EXCLI J, 2020;19:1512-1516.
    PMID: 33312109 DOI: 10.17179/excli2020-2964
  3. Globrauneine A-F: six new triterpenoid esters from the leaves of Globimetula braunii
    Muhammad KJ, Jamil S, Basar N, Sarker SD, Mohammed MG
    Nat Prod Res, 2020 Oct;34(19):2746-2753.
    PMID: 30931627 DOI: 10.1080/14786419.2019.1586693
    Phytochemical study was conducted on the leaves of Globimetula braunii which is a hemi parasitic plant belonging to the family Loranthaceae. Extraction was carried out using cold extraction method with increasing polarity of solvents i.e n-hexane, CH2Cl2 and MeOH. The components were separated by chromatographic technique and the structures of the compounds were elucidated by extensive spectroscopic analyses including MS, FTIR, 1D and 2D NMR, HRMS and chemical methods. Six new pentacyclic triterpenoid esters named as globrauneine A (1), globrauneine B (2), globrauneine C (3), globrauneine D (4), globrauneine E (5), and globrauneine F (6), together with six known compounds (7 - 12) were successfully isolated from the leaves of G. braunii growing on Piliostigma thonningii. These results depict a substantial support to the chemotaxonomy of the genus Globimetula.
  4. Rutin loaded liquid crystalline nanoparticles inhibit lipopolysaccharide induced oxidative stress and apoptosis in bronchial epithelial cells in vitro
    Paudel KR, Wadhwa R, Mehta M, Chellappan DK, Hansbro PM, Dua K
    Toxicol In Vitro, 2020 Oct;68:104961.
    PMID: 32771431 DOI: 10.1016/j.tiv.2020.104961
    Airway inflammation and infections are the primary causes of damage in the airway epithelium, that lead to hypersecretion of mucus and airway hyper-responsiveness. The role of reactive oxygen species (ROS) and their components in the pathophysiological mechanisms of airway inflammation have been well-studied and emphasized for the past several decades. Rutin, a potent bioflavonoid, is well-known for its antioxidant, anti-inflammatory, especially in bronchial inflammation. However, poor solubility and rapid metabolism have led to its low bioavailability in biological systems, and hence limit its application. The present study aims to investigate the beneficial effects of rutin-loaded liquid crystalline nanoparticles (LCNs) against lipopolysaccharide (LPS) induced oxidative damage in human bronchial epithelial cell line (BEAS-2-B) cells in vitro. LPS was used to stimulate BEAS-2-B cells, causing the generation of nitric oxide (NO) and other reactive oxygen species (ROS) that had led to cellular apoptosis. The levels of NO and ROS were detected by, Griess reagent kit and dichlorodihydrofluorescein diacetate (DCFH-DA) respectively, whereas, cell apoptosis was studied by Annexin V-FITC and PI staining. The findings revealed that rutin-loaded LCNs significantly reduced NO, ROS levels and prevented apoptosis in BEAS-2B cells. The observations and findings provide a mechanistic understanding of the effectiveness of rutin-loaded LCNs in protecting the bronchial cells against airway inflammation, thus possessing a promising therapeutic option for the management of airway diseases.
  5. Fulltext An Improved Fabrication Technique for the 3-D Frequency Selective Surface based on Water Transfer Printing Technology
    Harnois M, Himdi M, Yong WY, Rahim SKA, Tekkouk K, Cheval N
    Sci Rep, 2020 Feb 03;10(1):1714.
    PMID: 32015444 DOI: 10.1038/s41598-020-58657-5
    Manufacturing an array of high-quality metallic pattern layers on a dielectric substrate remains a major challenge in the development of flexible and 3-D frequency selective surfaces (FSS). This paper proposes an improved fabrication solution for the 3-D FSS based on water transfer printing (WTP) technology. The main advantages of the proposed solution are its ability to transform complicated 2-D planar FSS patterns into 3-D structures while improving both manufacturing quality and production costs. WTP technology makes use of water surface tension to keep the thin metallic patterns of the proposed FSS floating flat with the absence of a solid planar substrate. This feature enables these metallic FSS patterns to be transferred onto 3-D structures through a dipping process. To test the effectiveness of the proposed technique, the FSS was designed using computer simulation software Microwave Studio to obtain the numerical performance of the FSS structure. The WTP technology was then used to fabricate the proposed FSS prototype before its performance was tested experimentally. The measurement results agreed well with the numerical results, indicating the proposed manufacturing solution would support the development of complicated 3-D electronics devices, such as conformal antenna arrays and metamaterials.
  6. Neonatal herpes simplex virus type-1 central nervous system disease with acute retinal necrosis
    Fong CY, Aye AM, Peyman M, Nor NK, Visvaraja S, Tajunisah I, et al.
    Pediatr Infect Dis J, 2014 Apr;33(4):424-6.
    PMID: 24378951 DOI: 10.1097/INF.0000000000000137
    We report a case of neonatal herpes simplex virus (HSV)-1 central nervous system disease with bilateral acute retinal necrosis (ARN). An infant was presented at 17 days of age with focal seizures. Cerebrospinal fluid polymerase chain reaction was positive for HSV-1 and brain magnetic resonance imaging showed cerebritis. While receiving intravenous acyclovir therapy, the infant developed ARN with vitreous fluid polymerase chain reaction positive for HSV-1 necessitating intravitreal foscarnet therapy. This is the first reported neonatal ARN secondary to HSV-1 and the first ARN case presenting without external ocular or cutaneous signs. Our report highlights that infants with neonatal HSV central nervous system disease should undergo a thorough ophthalmological evaluation to facilitate prompt diagnosis and immediate treatment of this rapidly progressive sight-threatening disease.
  7. Patented therapeutic drug delivery strategies for targeting pulmonary diseases
    Thakur AK, Chellappan DK, Dua K, Mehta M, Satija S, Singh I
    Expert Opin Ther Pat, 2020 May;30(5):375-387.
    PMID: 32178542 DOI: 10.1080/13543776.2020.1741547
    Introduction: Pulmonary route is one of the preferred routes for the administration of therapeutically active agents for systemic as well as localized delivery. Chronic obstructive pulmonary disease (COPD), bronchial asthma, pneumonia, pulmonary hypertension, bronchiolitis, lung cancer, and tuberculosis are the major chronic diseases associated with the pulmonary system. Knowledge about the affecting factors, namely, the etiology, pathophysiology, and the various barriers (mechanical, chemical, immunological, and behavioral) in pulmonary drug delivery is essential to develop an effective drug delivery system. Formulation strategies and mechanisms of particle deposition in the lungs also play an important role in designing a suitable delivery system.Areas covered: In the present paper, various drug delivery strategies, viz. nanoparticles, microparticles, liposomes, powders, and microemulsions have been discussed systematically, from a patent perspective.Expert opinion: Patent publications on formulation strategies have been instrumental in the evolution of new techniques and technologies for safe and effective treatment of pulmonary diseases. New delivery systems are required to be simple/reproducible/scalable/cost-effective scale for manufacturing ability and should be safe/effective/stable/controllable for meeting quality and regulatory compliance.
  8. Fulltext miRNA nanotherapeutics: potential and challenges in respiratory disorders
    Mehta M, Chellappan DK, Wich PR, Hansbro NG, Hansbro PM, Dua K
    Future Med Chem, 2020 06;12(11):987-990.
    PMID: 32270706 DOI: 10.4155/fmc-2020-0066
  9. Fulltext Incipient need of targeting airway remodeling using advanced drug delivery in chronic respiratory diseases
    Mehta M, Satija S, Paudel KR, Liu G, Chellappan DK, Hansbro PM, et al.
    Future Med Chem, 2020 05;12(10):873-875.
    PMID: 32352313 DOI: 10.4155/fmc-2020-0091
  10. Fulltext The Effects of Lentivirus-Mediated Gene Silencing of RARβ on the Stemness Capability of Non-Small Cell Lung Cancer
    Abu Halim NH, Zakaria N, Theva Das K, Lin J, Lim MN, Fakiruddin KS, et al.
    J Cancer, 2021;12(12):3468-3485.
    PMID: 33995625 DOI: 10.7150/jca.50793
    Retinoic acid receptor beta is a nuclear receptor protein that binds to retinoic acid (RA) to mediate cellular signalling in embryogenic morphogenesis, cell growth, and differentiation. However, the function of RARβ in cancer stem cells (CSCs) has yet to be determined. This study aimed to understand the role of RARβ in regulating cell growth and differentiation of lung cancer stem cells. Based on the clonogenic assay, spheroid assay, mRNA levels of stem cell transcription factors, and cell cycle being arrested at the G0/G1 phase, the suppression of RARβ resulted in significant inhibition of A549 parental cell growth. This finding was contradictory to the results seen in CSCs, where RARβ inhibition enhanced the cell growth of putative and non-putative CSCs. These results suggest that RARβ suppression may act as an essential regulator in A549 parental cells, but not in the CSCs population. The findings in this study demonstrated that the loss of RARβ promotes tumorigenicity in CSCs. Microarray analysis revealed that various cancer pathways were significantly activated following the suppression of RARβ. The changes seen might compensate for the loss of RARβ function, CSCs population's aggressiveness, which led to the CSCs population's aggressiveness. Thus, understanding the role of RARβ in regulating the stemness of CSCs may lead to targeted therapy for lung CSCs.
  11. Fulltext Elliptical metallic rings-shaped fractal metamaterial absorber in the visible regime
    Bilal RMH, Saeed MA, Choudhury PK, Baqir MA, Kamal W, Ali MM, et al.
    Sci Rep, 2020 Aug 20;10(1):14035.
    PMID: 32820192 DOI: 10.1038/s41598-020-71032-8
    Achieving the broadband response of metamaterial absorbers has been quite challenging due to the inherent bandwidth limitations. Herein, the investigation was made of a unique kind of visible light metamaterial absorber comprising elliptical rings-shaped fractal metasurface using tungsten metal. It was found that the proposed absorber exhibits average absorption of over 90% in the visible wavelength span of 400-750 nm. The features of perfect absorption could be observed because of the localized surface plasmon resonance that causes impedance matching. Moreover, in the context of optoelectronic applications, the absorber yields absorbance up to ~ 70% even with the incidence obliquity in the range of 0°-60° for transverse electric polarization. The theory of multiple reflections was employed to further verify the performance of the absorber. The obtained theoretical results were found to be in close agreement with the simulation results. In order to optimize the results, the performance was analyzed in terms of the figure of merit and operating bandwidth. Significant amount of absorption in the entire visible span, wide-angle stability, and utilization of low-cost metal make the proposed absorber suitable in varieties of photonics applications, in particular photovoltaics, thermal emitters and sensors.
  12. Fulltext Projection of meteorological droughts in Nigeria during growing seasons under climate change scenarios
    Shiru MS, Shahid S, Dewan A, Chung ES, Alias N, Ahmed K, et al.
    Sci Rep, 2020 06 22;10(1):10107.
    PMID: 32572138 DOI: 10.1038/s41598-020-67146-8
    Like many other African countries, incidence of drought is increasing in Nigeria. In this work, spatiotemporal changes in droughts under different representative concentration pathway (RCP) scenarios were assessed; considering their greatest impacts on life and livelihoods in Nigeria, especially when droughts coincide with the growing seasons. Three entropy-based methods, namely symmetrical uncertainty, gain ratio, and entropy gain were used in a multi-criteria decision-making framework to select the best performing General Circulation Models (GCMs) for the projection of rainfall and temperature. Performance of four widely used bias correction methods was compared to identify a suitable method for correcting bias in GCM projections for the period 2010-2099. A machine learning technique was then used to generate a multi-model ensemble (MME) of the bias-corrected GCM projection for different RCP scenarios. The standardized precipitation evapotranspiration index (SPEI) was subsequently computed to estimate droughts from the MME mean of GCM projected rainfall and temperature to predict possible spatiotemporal changes in meteorological droughts. Finally, trends in the SPEI, temperature and rainfall, and return period of droughts for different growing seasons were estimated using a 50-year moving window, with a 10-year interval, to understand driving factors accountable for future changes in droughts. The analysis revealed that MRI-CGCM3, HadGEM2-ES, CSIRO-Mk3-6-0, and CESM1-CAM5 are the most appropriate GCMs for projecting rainfall and temperature, and the linear scaling (SCL) is the best method for correcting bias. The MME mean of bias-corrected GCM projections revealed an increase in rainfall in the south-south, southwest, and parts of the northwest whilst a decrease in the southeast, northeast, and parts of central Nigeria. In contrast, rise in temperature for entire country during most of the cropping seasons was projected. The results further indicated that increase in temperature would decrease the SPEI across Nigeria, which will make droughts more frequent in most of the country under all the RCPs. However, increase in drought frequency would be less for higher RCPs due to increase in rainfall.
  13. Applications and practice of advanced drug delivery systems for targeting Toll-like receptors in pulmonary diseases
    Chan Y, Prasher P, Löbenberg R, Gupta G, Singh SK, Oliver BG, et al.
    Nanomedicine (Lond), 2021 04;16(10):783-786.
    PMID: 33733817 DOI: 10.2217/nnm-2021-0056
  14. Fulltext Effect of multi-pronged interventions in reducing low birth weight and maternal anaemia among pregnant women. A community-based interventions research in non-agrarian resource constrained setting of rural Pakistan
    Thaver I, Ahmad AM, Ashraf M, Asghar SK, Mirza MS
    J Pak Med Assoc, 2020 Dec;70(12(A)):2092-2101.
    PMID: 33475578 DOI: 10.47391/JPMA.1218
    OBJECTIVE: To investigate the effect on maternal and infant health of iron plus folate and multiple micronutrient supplements, along with deworming and health education session provided to pregnant women in rural, nonagrarian and food-insecure areas.

    METHODS: The quasi-experimental study was conducted in Tharparker and Umerkot districts, Sindh, Pakistan, in 2013-14, and comprised pregnant women in their earlier weeks of pregnancy. The enrolment and follow-up phase entailed 3 visits to each subject. Areas covered by lady health workers were designated as intervention areas, and those with non-LHW population were labelled as non-intervention areas.

    RESULTS: Of the 1204 subjects, 600(49.8%) were in the intervention group and 604(50.2%) were in the nonintervention group. By the end of the follow-up phase, significantly more women had increased number of meals in the intervention group compared to the non-intervention group (p<0.001). There was a significantly higher increase in mean haemoglobin levels and body mass index of women in the intervention arm after 3 and 6 months of interventions (p<0.05). Significantly higher mean birth weight was recorded in intervention areas compared to nonintervention areas (p<0.05).

    CONCLUSIONS: Community-based provision of multiple micronutrients to women along with deworming, health education and dietary counselling significantly reduced the prevalence of anaemia and reduced the incidence of low birth weight.

  15. Emerging role of nanocarriers based topical delivery of anti-fungal agents in combating growing fungal infections
    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.
  16. Recent update on barbiturate in relation to brain disorder
    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
  17. Role of the Tristetraprolin (Zinc Finger Protein 36 Homolog) Gene in Cancer
    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.
  18. Sugar-based nanoparticles for respiratory diseases: a new paradigm in the nanoworld
    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
  19. Fulltext Whole-genome comparative analysis of Malaysian Burkholderia pseudomallei clinical isolates
    Ghazali AK, Eng SA, Khoo JS, Teoh S, Hoh CC, Nathan S
    Microb Genom, 2021 02;7(2).
    PMID: 33565959 DOI: 10.1099/mgen.0.000527
    Burkholderia pseudomallei, a soil-dwelling Gram-negative bacterium, is the causative agent of the endemic tropical disease melioidosis. Clinical manifestations of B. pseudomallei infection range from acute or chronic localized infection in a single organ to fulminant septicaemia in multiple organs. The diverse clinical manifestations are attributed to various factors, including the genome plasticity across B. pseudomallei strains. We previously characterized B. pseudomallei strains isolated in Malaysia and noted different levels of virulence in model hosts. We hypothesized that the difference in virulence might be a result of variance at the genome level. In this study, we sequenced and assembled four Malaysian clinical B. pseudomallei isolates, UKMR15, UKMPMC2000, UKMD286 and UKMH10. Phylogenomic analysis showed that Malaysian subclades emerged from the Asian subclade, suggesting that the Malaysian strains originated from the Asian region. Interestingly, the low-virulence strain, UKMH10, was the most distantly related compared to the other Malaysian isolates. Genomic island (GI) prediction analysis identified a new island of 23 kb, GI9c, which is present in B. pseudomallei and Burkholderia mallei, but not Burkholderia thailandensis. Genes encoding known B. pseudomallei virulence factors were present across all four genomes, but comparative analysis of the total gene content across the Malaysian strains identified 104 genes that are absent in UKMH10. We propose that these genes may encode novel virulence factors, which may explain the reduced virulence of this strain. Further investigation on the identity and role of these 104 proteins may aid in understanding B. pseudomallei pathogenicity to guide the design of new therapeutics for treating melioidosis.
  20. Probing the effects of fish oil on the delivery and inflammation-inducing potential of imiquimod
    Rehman K, Aluwi MF, Rullah K, Wai LK, Mohd Amin MC, Zulfakar MH
    Int J Pharm, 2015 Jul 25;490(1-2):131-41.
    PMID: 26003416 DOI: 10.1016/j.ijpharm.2015.05.045
    Imiquimod is a chemotherapeutic agent for many skin-associated diseases, but it has also been associated with inflammatory side effects. The aim of this study was to prevent the inflammatory effect of commercial imiquimod (Aldara(®)) by controlled release of imiquimod through a hydrogel/oleogel colloidal mixture (CA bigel) containing fish oil as an anti-inflammatory agent. Imiquimod permeability from Aldara® cream and bigel through mice skin was evaluated, and the drug content residing in the skin via the tape stripping technique was quantified. The fish oil fatty acid content in skin along with its lipophilic environment was also determined. An inflammation study was conducted using animal models, and Aldara(®) cream was found to potentially cause psoriasis-like inflammation, which could be owing to prolonged application and excessive drug permeation. Controlled release of imiquimod along with fish oil through CA bigel may have caused reduced imiquimod inflammation. NMR studies and computerized molecular modeling were also conducted to observe whether the fish oil and imiquimod formed a complex that was responsible for improving imiquimod transport and reducing its side effects. NMR spectra showed dose-dependent chemical shifts and molecular modeling revealed π-σ interaction between EPA and imiquimod, which could help reduce imiquimod inflammation.
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