Displaying all 17 publications

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  1. Shah K, Chan LW, Wong TW
    Drug Deliv, 2017 Nov;24(1):1631-1647.
    PMID: 29063794 DOI: 10.1080/10717544.2017.1384298
    The study investigated aerosolization, pulmonary inhalation, intracellular trafficking potential in macrophages and pharmacokinetics profiles of rifampicin-oleic acid first-generation nanoemulsion and its respective chitosan- and chitosan-folate conjugate-decorated second and third-generation nanoemulsions, delivered via nebulization technique. The nanoemulsions were prepared by conjugate synthesis and spontaneous emulsification techniques. They were subjected to physicochemical, drug release, aerosolization, inhalation, cell culture and pharmacokinetics analysis. The nanoemulsions had average droplet sizes of 40-60 nm, with narrow polydispersity indices. They exhibited desirable pH, surface tension, viscosity, refractive index, density and viscosity attributes for pulmonary rifampicin administration. All nanoemulsions demonstrated more than 95% aerosol output and inhalation efficiency greater than 75%. The aerosol output, aerosolized and inhaled fine particle fractions were primarily governed by the size and surface tension of nanoemulsions in an inverse relationship. The nanoemulsions were found to be safe with third-generation nanoemulsion exhibiting higher cell internalization potential, reduced plasma drug concentration, and higher lung drug content.
  2. Shah K, Chan LW, Wong TW
    Int J Biol Macromol, 2023 Sep 21;253(Pt 4):126991.
    PMID: 37739286 DOI: 10.1016/j.ijbiomac.2023.126991
    Solid particles ≤5 μm are essential to allow lower lung deposition and macrophage phagocytosis of anti-tubercular drugs. Decorating liquid nanoemulsion of anti-tubercular drug with macrophage-specific chitosan and chitosan-folate conjugate and spray drying the nanoemulsion with lactose produced oversized solid particles due to polysaccharide binding effects. This study designed solid nanoemulsion using lactose as the primary solid carrier and explored additives and spray-drying variables to reduce the binding and particle growth effects of chitosan. Deposition of magnesium stearate on lactose negated chitosan-inducible excessive lactose-liquid nanoemulsion binding and solid particle growth. Moderating the adhesion of chitosan-decorated liquid nanoemulsion onto lactose produced smooth-surface solid microparticles (size: 5.45 ± 0.26 μm; roughness: ∼80 nm) with heterogeneous size (span: 1.87 ± 1.21) through plasticization of constituent materials of nanoemulsion and lactose involving OH/N-H, C-H, CONH and/or COO moieties. Smaller solid particles could attach onto the larger particles with minimal steric hindrance by smooth surfaces. Together with round solid particulate structures (circularity: 0.919 ± 0.002), good pulmonary inhalation beneficial for treatment of pulmonary tuberculosis as well as other diseases is conferred.
  3. Ahmad S, Ullah A, Shah K, Salahshour S, Ahmadian A, Ciano T
    Adv Differ Equ, 2020;2020(1):472.
    PMID: 32922446 DOI: 10.1186/s13662-020-02934-0
    In this paper, a novel coronavirus infection system with a fuzzy fractional differential equation defined in Caputo's sense is developed. By using the fuzzy Laplace method coupled with Adomian decomposition transform, numerical results are obtained for better understanding of the dynamical structures of the physical behavior of COVID-19. Such behavior on the general properties of RNA in COVID-19 is also investigated for the governing model. The results demonstrate the efficiency of the proposed approach to address the uncertainty condition in the pandemic situation.
  4. Ahmad W, Sarwar M, Shah K, Ahmadian A, Salahshour S
    Math Methods Appl Sci, 2021 Feb 03.
    PMID: 33821069 DOI: 10.1002/mma.7241
    In this manuscript, the mathematical model of COVID-19 is considered with eight different classes under the fractional-order derivative in Caputo sense. A couple of results regarding the existence and uniqueness of the solution for the proposed model is presented. Furthermore, the fractional-order Taylor's method is used for the approximation of the solution of the concerned problem. Finally, we simulate the results for 50 days with the help of some available data for fractional differential order to display the excellency of the proposed model.
  5. Shah K, Arfan M, Mahariq I, Ahmadian A, Salahshour S, Ferrara M
    Results Phys, 2020 Dec;19:103560.
    PMID: 33200064 DOI: 10.1016/j.rinp.2020.103560
    This work is the consideration of a fractal fractional mathematical model on the transmission and control of corona virus (COVID-19), in which the total population of an infected area is divided into susceptible, infected and recovered classes. We consider a fractal-fractional order

    SIR

    type model for investigation of Covid-19. To realize the transmission and control of corona virus in a much better way, first we study the stability of the corresponding deterministic model using next generation matrix along with basic reproduction number. After this, we study the qualitative analysis using "fixed point theory" approach. Next, we use fractional Adams-Bashforth approach for investigation of approximate solution to the considered model. At the end numerical simulation are been given by matlab to provide the validity of mathematical system having the arbitrary order and fractal dimension.
  6. Chachuli SH, Nawaz A, Shah K, Naharudin I, Wong TW
    Pharm Res, 2016 06;33(6):1497-508.
    PMID: 26951565 DOI: 10.1007/s11095-016-1893-5
    PURPOSE: Pulmonary infection namely tuberculosis is characterized by alveolar macrophages harboring a large microbe population. The chitosan nanoparticles exhibit fast extracellular drug release in aqueous biological milieu. This study investigated the matrix effects of chitosan nanoparticles on extracellular drug diffusion into macrophages.

    METHODS: Oligo, low, medium and high molecular weight chitosan nanoparticles were prepared by nanospray drying technique. These nanoparticles were incubated with alveolar macrophages in vitro and had model drug sodium fluorescein added into the same cell culture. The diffusion characteristics of sodium fluorescein and nanoparticle behavior were investigated using fluorescence microscopy, scanning electron microscopy, differential scanning calorimetry and Fourier transform infrared spectroscopy techniques.

    RESULTS: The oligochitosan nanoparticles enabled macrophage membrane fluidization with the extent of sodium fluorescein entry into macrophages being directly governed by the nanoparticle loading. Using nanoparticles made of higher molecular weight chitosan, sodium fluorescein permeation into macrophages was delayed due to viscous chitosan diffusion barrier at membrane boundary.

    CONCLUSION: Macrophage-chitosan nanoparticle interaction at membrane interface dictates drug migration into cellular domains.

  7. Rasul RM, Tamilarasi Muniandy M, Zakaria Z, Shah K, Chee CF, Dabbagh A, et al.
    Carbohydr Polym, 2020 Dec 15;250:116800.
    PMID: 33049807 DOI: 10.1016/j.carbpol.2020.116800
    Chitosan, as a biodegradable and biocompatible polymer, is characterized by anti-microbial and anti-cancer properties. It lately has received a widespread interest for use as the pulmonary particulate backbone materials of drug carrier for the treatment of infectious disease and cancer. The success of chitosan as pulmonary particulate drug carrier is a critical interplay of their mucoadhesive, permeation enhancement and site/cell-specific attributes. In the case of nanocarriers, various microencapsulation and micro-nano blending systems have been devised to equip them with an appropriate aerodynamic character to enable efficient pulmonary aerosolization and inhalation. The late COVID-19 infection is met with acute respiratory distress syndrome and cancer. Chitosan and its derivatives are found useful in combating HCoV and cancer as a function of their molecular weight, substituent type and its degree of substitution. The interest in chitosan is expected to rise in the next decade from the perspectives of drug delivery in combination with its therapeutic performance.
  8. Sharma R, Agarwal P, Jain V, Sagili H, Sarkar S, Panda A, et al.
    J Obstet Gynaecol India, 2023 Dec;73(6):477-487.
    PMID: 38205114 DOI: 10.1007/s13224-023-01838-9
    BACKGROUND: During the Covid-19 pandemic, reproductive health of women was disproportionately affected due to difficult access to safe abortion and contraceptive services. This study aims to assess the impact of the Covid-19 pandemic on the prevalence of MTP cases and to find out the clinicodemographic profiles of women undergoing MTP during three Covid-waves in different hospitals-Government and private sectors in India.

    METHODS: This retrospective multicentric cohort study was conducted during three Covid-19 pandemic waves. The records were retrieved from the centers' medical record section and the MTP register from the Department of Obstetrics and Gynaecology.

    RESULTS: On an average, 1.1 women/day underwent MTP during covid waves compared to 1.9 women/day during the pre-covid 2019. The first Covid wave's average MTP/day was very low (0.71) compared to the third (2.88) and second wave (1.12), respectively. These differences were statistically significant (p<0.0001). The most common indication for MTP was contraceptive failure 245(50.9%), followed by eugenic/congenital anomalies 88(18.9%). A total of 244 cases (50.6%) reported for MTP ≤ seven weeks and 114(23.6%) presented between 7 and 12 weeks. More than half (54%) of the women underwent surgical methods for abortion as the unavailability of medical abortion (MA) drugs. IUCD and sterilization were severely affected during the first and second Covid waves.

    CONCLUSION: Safe abortions are essential services for reproductive-age women. With the uncertainty of future Covid-like an emergency, we should strengthen our telemedicine network so that women can reach out early and MMA can be initiated to reduce the number of surgical abortions and unwanted pregnancies.

  9. Shah K, Sher M, Rabai'ah H, Ahmadian A, Salahshour S, Pansera BA
    Math Methods Appl Sci, 2021 Aug 22.
    PMID: 34908635 DOI: 10.1002/mma.7704
    In the current article, we aim to study in detail a novel coronavirus (2019-nCoV or COVID-19) mathematical model for different aspects under Caputo fractional derivative. First, from analysis point of view, existence is necessary to be investigated for any applied problem. Therefore, we used fixed point theorem's due to Banach's and Schaefer's to establish some sufficient results regarding existence and uniqueness of the solution to the proposed model. On the other hand, stability is important in respect of approximate solution, so we have developed condition sufficient for the stability of Ulam-Hyers and their different types for the considered system. In addition, the model has also been considered for semianalytical solution via Laplace Adomian decomposition method (LADM). On Matlab, by taking some real data about Pakistan, we graph the obtained results. In the last of the manuscript, a detail discussion and brief conclusion are provided.
  10. Zamir M, Shah K, Nadeem F, Bajuri MY, Ahmadian A, Salahshour S, et al.
    Results Phys, 2021 Feb;21:103784.
    PMID: 36465528 DOI: 10.1016/j.rinp.2020.103784
    This article focus the elimination and control of the infection caused by COVID-19. Mathematical model of the disease is formulated. With help of sensitivity analysis of the reproduction number the most sensitive parameters regarding transmission of infection are found. Consequently strategies for the control of infection are proposed. Threshold condition for global stability of the disease free state is investigated. Finally, using Matlab numerical simulations are produced for validation of theocratical results.
  11. Lee YH, Pang SW, Revai Lechtich E, Shah K, Simon SE, Ponnusamy S, et al.
    J Cancer Res Clin Oncol, 2020 Jul;146(7):1751-1764.
    PMID: 32377840 DOI: 10.1007/s00432-020-03231-9
    PURPOSE: Although important for apoptosis, the signaling pathway involving MOAP-1(Modulator of Apoptosis 1), RASSF1A (RAS association domain family 1A), and Bax (Bcl-2 associated X protein) is likely to be dysfunctional in many types of human cancers due to mechanisms associated with gene mutation and DNA hyper-methylation. The purpose of the present study was to assess the potential impact of generating physiologically relevant signaling pathway mediated by MOAP-1, Bax, and RASSF1A (MBR) in cancer cells and chemo-drug resistant cancer cells.

    METHODS: The tricistronic expression construct that encodes MOAP-1, Bax, and RASSF1A (MBR) or its mutant, MOAP-1∆BH3L, Bax and RASSF1A (MBRX) was expressed from an IRES (Internal Ribosome Entry Site)-based tricistronic expression vector in human breast cancer cells, including MCF-7, MCF-7-CR (cisplatin resistant) and triple negative breast cancer cells, BMET05, for functional characterization through in vitro and in vivo models.

    RESULTS: Transient expression of MBR potently promoted dose-dependent apoptotic signaling and chemo-sensitization in the cancer cells, as evidenced by loss of cell viability, nuclei condensation and Annexin-V positive staining while stable expression of MBR in MCF-7 cells significantly reduced the number of MBR stable clone by 86% and the stable clone exhibited robust chemo-drug sensitivity. In contrast, MBRX stable clone exhibited chemo-drug resistance while transiently over-expressed MOAP-1ΔBH3L inhibited the apoptotic activity of MBR. Moreover, the spheroids derived from the MBR stable clone displayed enhanced chemo-sensitivity and apoptotic activity. In mouse xenograft model, the tumors derived from MBR stable clone showed relatively high level of tumor growth retardation associated with the increase in apoptotic activity, leading to the decreases in both tumor weight and volume.

    CONCLUSIONS: Expression of MBR in cancer cells induces apoptotic cell death with enhanced chemo-sensitization requiring the BH3L domain of MOAP-1. In animal model, the expression of MBR significantly reduces the growth of tumors, suggesting that MBR is a potent apoptotic sensitizer with potential therapeutic benefits for cancer treatment.

  12. Suleman M, Ahmad T, Shah K, Albekairi NA, Alshammari A, Khan A, et al.
    Front Pharmacol, 2023;14:1328308.
    PMID: 38269277 DOI: 10.3389/fphar.2023.1328308
    Amid the ongoing monkeypox outbreak, there is an urgent need for the rapid development of effective therapeutic interventions capable of countering the immune evasion mechanisms employed by the monkeypox virus (MPXV). The evasion strategy involves the binding of the F3L protein to dsRNA, resulting in diminished interferon (IFN) production. Consequently, our current research focuses on utilizing virtual drug screening techniques to target the RNA binding domain of the F3L protein. Out of the 954 compounds within the South African natural compound database, only four demonstrated notable docking scores: -6.55, -6.47, -6.37, and -6.35 kcal/mol. The dissociation constant (KD) analysis revealed a stronger binding affinity of the top hits 1-4 (-5.34, -5.32, -5.29, and -5.36 kcal/mol) with the F3L in the MPXV. All-atom simulations of the top-ranked hits 1 to 4 consistently exhibited stable dynamics, suggesting their potential to interact effectively with interface residues. This was further substantiated through analyses of parameters such as radius of gyration (Rg), Root Mean Square Fluctuation, and hydrogen bonding. Cumulative assessments of binding free energy confirmed the top-performing candidates among all the compounds, with values of -35.90, -52.74, -28.17, and -32.11 kcal/mol for top hits 1-4, respectively. These results indicate that compounds top hit 1-4 could hold significant promise for advancing innovative drug therapies, suggesting their suitability for both in vivo and in vitro experiments.
  13. Stebbing J, Shah K, Lit LC, Gagliano T, Ditsiou A, Wang T, et al.
    Oncogene, 2018 06;37(23):3113-3130.
    PMID: 29540829 DOI: 10.1038/s41388-018-0197-0
    Lemur tyrosine kinase 3 (LMTK3) is an oncogenic kinase that is involved in different types of cancer (breast, lung, gastric, colorectal) and biological processes including proliferation, invasion, migration, chromatin remodeling as well as innate and acquired endocrine resistance. However, the role of LMTK3 in response to cytotoxic chemotherapy has not been investigated thus far. Using both 2D and 3D tissue culture models, we found that overexpression of LMTK3 decreased the sensitivity of breast cancer cell lines to cytotoxic (doxorubicin) treatment. In a mouse model we showed that ectopic overexpression of LMTK3 decreases the efficacy of doxorubicin in reducing tumor growth. Interestingly, breast cancer cells overexpressing LMTK3 delayed the generation of double strand breaks (DSBs) after exposure to doxorubicin, as measured by the formation of γH2AX foci. This effect was at least partly mediated by decreased activity of ataxia-telangiectasia mutated kinase (ATM) as indicated by its reduced phosphorylation levels. In addition, our RNA-seq analyses showed that doxorubicin differentially regulated the expression of over 700 genes depending on LMTK3 protein expression levels. Furthermore, these genes were found to promote DNA repair, cell viability and tumorigenesis processes / pathways in LMTK3-overexpressing MCF7 cells. In human cancers, immunohistochemistry staining of LMTK3 in pre- and post-chemotherapy breast tumor pairs from four separate clinical cohorts revealed a significant increase of LMTK3 following both doxorubicin and docetaxel based chemotherapy. In aggregate, our findings show for the first time a contribution of LMTK3 in cytotoxic drug resistance in breast cancer.
  14. Srivastava A, Sharma A, Jena MK, Vuppaladadiyam AK, Reguyal F, Joshi J, et al.
    Sci Total Environ, 2024 Oct 10;946:174167.
    PMID: 38917898 DOI: 10.1016/j.scitotenv.2024.174167
    Globally, COVID-19 has not only caused tremendous negative health, social and economic impacts, but it has also led to environmental issues such as a massive increase in biomedical waste. The biomedical waste (BMW) was generated from centralized (hospitals, clinics, and research facilities) and extended (quarantine camps, COVID-19 test camps, and quarantined homes) healthcare facilities. Many effects, such as the possibility of infection spread, unlawful dumping/disposal, and an increase in toxic emissions by common BMW treatment facilities, are conjectured because of the rise in waste generation. However, it is also an opportunity to critically analyze the current BMW treatment scenario and implement changes to make the system more economical and environmentally sustainable. In this review, the waste disposal guidelines of the BMW management infrastructure are critically analyzed for many functional parameters to bring out possible applications and limitations of individual interventions. In addition, an investigation was made to select appropriate technology based on the environmental setting.
  15. Rogers SN, Alvear A, Anesi A, Babin E, Balik A, Batstone M, et al.
    Head Neck, 2020 03;42(3):498-512.
    PMID: 31833121 DOI: 10.1002/hed.26027
    BACKGROUND: The aim was to collate and contrast patient concerns from a range of different head and neck cancer follow-up clinics around the world. Also, we sought to explore the relationship, if any, between responses to the patient concerns inventory (PCI) and overall quality of life (QOL).

    METHODS: Nineteen units participated with intention of including 100 patients per site as close to a consecutive series as possible in order to minimize selection bias.

    RESULTS: There were 2136 patients with a median total number of PCI items selected of 5 (2-10). "Fear of the cancer returning" (39%) and "dry mouth" (37%) were most common. Twenty-five percent (524) reported less than good QOL.

    CONCLUSION: There was considerable variation between units in the number of items selected and in overall QOL, even after allowing for case-mix variables. There was a strong progressive association between the number of PCI items and QOL.

  16. Chew NWS, Ngiam JN, Tan BY, Tham SM, Tan CY, Jing M, et al.
    BJPsych Open, 2020 Oct 08;6(6):e116.
    PMID: 33028449 DOI: 10.1192/bjo.2020.98
    BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has led to significant strain on front-line healthcare workers.

    AIMS: In this multicentre study, we compared the psychological outcomes during the COVID-19 pandemic in various countries in the Asia-Pacific region and identified factors associated with adverse psychological outcomes.

    METHOD: From 29 April to 4 June 2020, the study recruited healthcare workers from major healthcare institutions in five countries in the Asia-Pacific region. A self-administrated survey that collected information on prior medical conditions, presence of symptoms, and scores on the Depression Anxiety Stress Scales and the Impact of Events Scale-Revised were used. The prevalence of depression, anxiety, stress and post-traumatic stress disorder (PTSD) relating to COVID-19 was compared, and multivariable logistic regression identified independent factors associated with adverse psychological outcomes within each country.

    RESULTS: A total of 1146 participants from India, Indonesia, Singapore, Malaysia and Vietnam were studied. Despite having the lowest volume of cases, Vietnam displayed the highest prevalence of PTSD. In contrast, Singapore reported the highest case volume, but had a lower prevalence of depression and anxiety. In the multivariable analysis, we found that non-medically trained personnel, the presence of physical symptoms and presence of prior medical conditions were independent predictors across the participating countries.

    CONCLUSIONS: This study highlights that the varied prevalence of psychological adversity among healthcare workers is independent of the burden of COVID-19 cases within each country. Early psychological interventions may be beneficial for the vulnerable groups of healthcare workers with presence of physical symptoms, prior medical conditions and those who are not medically trained.

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