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  1. Wong CC, Sagineedu SR, Sumon SH, Sidik SM, Phillips R, Lajis NH, et al.
    Environ Toxicol Pharmacol, 2014 Sep;38(2):489-501.
    PMID: 25168151 DOI: 10.1016/j.etap.2014.07.016
    Andrographolide (AGP) is the main bioactive constituent isolated from the traditional medicinal, Andrographis paniculata which contributes towards its various biological activities, including anticancer property. In this study, a series of new AGP derivatives were semi-synthesised and screened against the NCI in vitro 60 cell lines. From the screening results, we had identified SRS07 as the most potent AGP derivative, against breast and colon cancer cell lines. Subsequently, SRS07 was tested for its capability to induce cell cycle arrest and apoptosis in MCF-7 and HCT116 cancer cells. SRS07 effectively induced G1 cell cycle arrest in both cell lines and ultimately apoptosis by inducing DNA fragmentation in HCT116 cells. The apoptotic cell death induced by SRS07 was confirmed via FITC Annexin-V double staining. Western blot analysis of SRS07-treated HCT116 cells revealed that the compound induced apoptosis be activating caspase 8 which in turn cleaved Bid to t-Bid to initiate cell death cascade. Prediction of the possible mode of action of SRS07 by utilising NCI COMPARE analysis failed to reveal a distinct mechanism category. Hence, it is speculated that SRS07 possesses novel mechanism of action. In conclusion, SRS07 demonstrated superior in vitro anticancer profiles and emerged as a potential lead anticancer candidate.
  2. Wong CC, Periasamy N, Sagineedu SR, Sidik S, Sumon SH, Loadman P, et al.
    Invest New Drugs, 2014 Oct;32(5):806-14.
    PMID: 24875131 DOI: 10.1007/s10637-014-0105-6
    Limited tumor penetrability of anti-cancer drugs is recognized as one of the major factors that lead to poor anti-tumor activity. SRJ09 (3,19-(2-bromobenzylidene) andrographolide) has been identified as a lead anti-cancer agent for colon cancer. Recently, this compound was shown by us to be a mutant K-Ras binder. In this present study, the penetrability of SRJ09 through the DLD-1 colon cancer multicell layer (MCL) was evaluated. The amount of SRJ09 that penetrated through the MCL was quantitated by utilizing high performance liquid chromatography (HPLC). Histopathological staining was used to visualize the morphology of MCL. A chemosensitivity assay was performed to assess the anti-cancer activity of SRJ09 in DLD-1 cells. SRJ09 was able to penetrate through DLD-1 MCL and is inversely proportional with the MCL thickness. The flow rates for SRJ09 through MCL were 0.90 ± 0.20 μM/min/cm(2) and 0.56 ± 0.06 μM/min/cm(2) for days 1 and 5, respectively, which are better than doxorubicin. Histopathological examination revealed that the integrity of the DLD-1 MCL was retained and no visible damage was inflicted on the cell membrane, confirming the penetration of SRJ09 was by diffusion. Short term exposure (1 h) in DLD-1 cells demonstrated SRJ09 had IC50 of 41 μM which was approximately 4-folds lower than andrographolide, the parent compound of SRJ09. In conclusion, SRJ09 successfully penetrated through DLD-1 MCL by diffusion and emerged as a potential candidate to be developed as a clinically viable anti-colon cancer drug.
  3. Huang L, Ahmad NH, Juneja V, Stapp-Kamotani E, Gabiola J, Minocha U, et al.
    Food Microbiol, 2024 Apr;118:104420.
    PMID: 38049265 DOI: 10.1016/j.fm.2023.104420
    During commercial production of liquid egg yolk (LEY), phospholipase A2 (PLA2) is used to improve its emulsification capacity and thermal stability. The enzymatic treatment may occur at elevated temperatures such as 50 °C, potentially allowing foodborne pathogens, such as Bacillus cereus, to grow. Little knowledge is available concerning growth of B. cereus in LEY during PLA2 treatment. Therefore, the objective of this study was to investigate the growth kinetics of B. cereus during PLA2 treatment using pathogenic B. cytotoxicus NVH391-98, the most thermotolerant member in the B. cereus group, as a surrogate. Inoculated LEY samples were placed in precision programmable incubators to observe the growth of B. cytotoxicus NVH391-98 under multiple isothermal and dynamic temperature conditions between 20 and 53 °C. The bacterial growth was described using the differential Baranyi model coupled with two different secondary models. The kinetic parameters were determined using one-step dynamic inverse analysis of multiple growth curves. The least square method was used in combination with the 4th order Runge-Kutta method to solve the differential Baranyi model using multiple growth curves to determine the cardinal kinetic parameters. The results showed that B. cytotoxicus NVH391-98 can grow prolifically at 50 °C. The estimated minimum, optimum and maximum temperatures were 16.7 or 18.5, 47.8 or 48.1, and 52.1 or 52.4 °C, respectively, depending on the secondary models, with an optimum growth rate of 2.1 log colony-forming-unit (CFU)/g per hour. The dynamic model is validated using isothermal curves with reasonable accuracy. B. cytotoxicus died off slowly at 15 °C. At 55 °C, thermal inactivation was observed, with a D value of approximately 2.7 h. Holding at 55 °C or below 15 °C can effectively prevent the growth of B. cytotoxicus in egg yolk.
  4. Tham LP, Wah W, Phillips R, Shahidah N, Ng YY, Shin SD, et al.
    Resuscitation, 2018 04;125:111-117.
    PMID: 29421664 DOI: 10.1016/j.resuscitation.2018.01.040
    BACKGROUND: The Pan Asian Resuscitation Outcomes Study (PAROS) is a retrospective study of out- of-hospital cardiac arrest(OHCA), collaborating with EMS agencies and academic centers in Japan, South Korea, Malaysia, Singapore, Taiwan, Thailand and UAE-Dubai. The objectives of this study is to describe the characteristics and outcomes, and to find factors associated with survival after paediatric OHCA.

    METHODS: We studied all children less than 17 years of age with OHCA conveyed by EMS and non-EMS transports from January 2009 to December 2012. We did univariate and multivariate logistic regression analyses to assess the factors associated with survival-to-discharge outcomes.

    RESULTS: A total of 974 children with OHCA were included. Bystander cardiopulmonary resuscitation rates ranged from 53.5% (Korea), 35.6% (Singapore) to 11.8% (UAE). Overall, 8.6% (range 0%-9.7%) of the children survived to discharge from hospital. Adolescents (13-17 years) had the highest survival rate of 13.8%. 3.7% of the children survived with good neurological outcomes of CPC 1 or 2. The independent pre-hospital factors associated with survival to discharge were witnessed arrest and initial shockable rhythm. In the sub-group analysis, pre-hospital advanced airway [odds ratio (OR) = 3.35, 95% confidence interval (CI) = 1.23-9.13] was positively associated with survival-to-discharge outcomes in children less than 13 years-old. Among adolescents, bystander CPR (OR = 2.74, 95%CI = 1.03-7.3) and initial shockable rhythm (OR = 20.51, 95%CI = 2.15-195.7) were positive factors.

    CONCLUSION: The wide variation in the survival outcomes amongst the seven countries in our study may be due to the differences in the delivery of pre-hospital interventions and bystander CPR rates.

  5. Essery R, Pollet S, Smith KA, Mowbray F, Slodkowska-Barabasz J, Denison-Day J, et al.
    Pilot Feasibility Stud, 2021 Aug 18;7(1):158.
    PMID: 34407886 DOI: 10.1186/s40814-021-00884-2
    BACKGROUND: By 2050, worldwide dementia prevalence is expected to triple. Affordable, scalable interventions are required to support protective behaviours such as physical activity, cognitive training and healthy eating. This paper outlines the theory-, evidence- and person-based development of 'Active Brains': a multi-domain digital behaviour change intervention to reduce cognitive decline amongst older adults.

    METHODS: During the initial planning phase, scoping reviews, consultation with PPI contributors and expert co-investigators and behavioural analysis collated and recorded evidence that was triangulated to inform provisional 'guiding principles' and an intervention logic model. The following optimisation phase involved qualitative think aloud and semi-structured interviews with 52 older adults with higher and lower cognitive performance scores. Data were analysed thematically and informed changes and additions to guiding principles, the behavioural analysis and the logic model which, in turn, informed changes to intervention content.

    RESULTS: Scoping reviews and qualitative interviews suggested that the same intervention content may be suitable for individuals with higher and lower cognitive performance. Qualitative findings revealed that maintaining independence and enjoyment motivated engagement in intervention-targeted behaviours, whereas managing ill health was a potential barrier. Social support for engaging in such activities could provide motivation, but was not desirable for all. These findings informed development of intervention content and functionality that appeared highly acceptable amongst a sample of target users.

    CONCLUSIONS: A digitally delivered intervention with minimal support appears acceptable and potentially engaging to older adults with higher and lower levels of cognitive performance. As well as informing our own intervention development, insights obtained through this process may be useful for others working with, and developing interventions for, older adults and/or those with cognitive impairment.

  6. Johnson CD, Green BN, Agaoglu M, Amorin-Woods L, Brown R, Byfield D, et al.
    J Chiropr Humanit, 2023 Dec;30:23-45.
    PMID: 37841068 DOI: 10.1016/j.echu.2023.08.001
    OBJECTIVE: This study aimed to (1) collect and analyze statements about how to celebrate chiropractic in the present and roles that chiropractors may fulfill in the future, (2) identify if there was congruence among the themes between present and future statements, and (3) offer a model about the chiropractic profession that captures its complex relationships that encompass its interactions within microsystem, mesosystem, exosystem, and macrosystem levels.

    METHODS: For this qualitative analysis, we used pattern and grounded theory approaches. A purposive sample of thought leaders in the chiropractic profession were invited to answer the following 2 open-ended questions: (1) envision the chiropractor of the future, and (2) recommendations on how to celebrate chiropractic. Information was collected during April 2023 using Survey Monkey. The information was entered into a spreadsheet and analyzed for topic clusters, which resulted in matching concepts with social-ecological themes. The themes between the responses to the 2 questions were analyzed for congruence. We used the Standards for Reporting Qualitative Research to report our findings.

    RESULTS: Of the 54 experts invited, 32 (59%) participated. Authors represented 7 countries and have a median of 32 years of chiropractic experience, with a range of 5 to 51 years. Nineteen major topics in the future statements and 23 major topics in statements about celebrating chiropractic were combined in a model. The topics were presented using the 4 levels of the social-ecological framework. Individual (microsystem): chiropractors are competent, well-educated experts in spine and musculoskeletal care who apply evidence-based practices, which is a combination of the best available evidence, clinical expertise, and patient values. Interpersonal relationships (mesosystem): chiropractors serve the best interests of their patients, provide person-centered care, embrace diversity, equity, and inclusion, consider specific health needs and the health of the whole person. Community (exosystem): chiropractors provide care within integrated health care environments and in private practices, serve the best interests of the public through participation in their communities, participate through multidisciplinary collaboration with and within the health care system, and work together as a profession with a strong professional identity. Societal (macrosystem): chiropractors contribute to the greater good of society and participate on a global level in policy, leadership, and research. There was concordance between both the future envisioning statements and the present celebration recommendations, which suggest logical validity based on the congruence of these concepts.

    CONCLUSION: A sample of independent views, including the perceptions from a broad range of chiropractic thought leaders from various backgrounds, philosophies, diversity characteristics, and world regions, were assembled to create a comprehensive model of the chiropractic profession. The resulting model shows an array of intrinsic values and provides the roles that chiropractors may provide to serve patients and the public. This study offers insights into the roles that future chiropractors may fulfill and how these are congruent with present-day values. These core concepts and this novel model may have utility during dialogs about identity, applications regarding chiropractic in policy, practice, education, and research, and building positive relationships and collaborations.

  7. Maaroufi A, Vince A, Himatt SM, Mohamed R, Fung J, Opare-Sem O, et al.
    J Viral Hepat, 2017 10;24 Suppl 2:8-24.
    PMID: 29105285 DOI: 10.1111/jvh.12762
    Due to the introduction of newer, more efficacious treatment options, there is a pressing need for policy makers and public health officials to develop or adapt national hepatitis C virus (HCV) control strategies to the changing epidemiological landscape. To do so, detailed, country-specific data are needed to characterize the burden of chronic HCV infection. In this study of 17 countries, a literature review of published and unpublished data on HCV prevalence, viraemia, genotype, age and gender distribution, liver transplants and diagnosis and treatment rates was conducted, and inputs were validated by expert consensus in each country. Viraemic prevalence in this study ranged from 0.2% in Hong Kong to 2.4% in Taiwan, while the largest viraemic populations were in Nigeria (2 597 000 cases) and Taiwan (569 000 cases). Diagnosis, treatment and liver transplant rates varied widely across the countries included in this analysis, as did the availability of reliable data. Addressing data gaps will be critical for the development of future strategies to manage and minimize the disease burden of hepatitis C.
  8. Chan HLY, Chen CJ, Omede O, Al Qamish J, Al Naamani K, Bane A, et al.
    J Viral Hepat, 2017 10;24 Suppl 2:25-43.
    PMID: 29105283 DOI: 10.1111/jvh.12760
    Factors influencing the morbidity and mortality associated with viremic hepatitis C virus (HCV) infection change over time and place, making it difficult to compare reported estimates. Models were developed for 17 countries (Bahrain, Bulgaria, Cameroon, Colombia, Croatia, Dominican Republic, Ethiopia, Ghana, Hong Kong, Jordan, Kazakhstan, Malaysia, Morocco, Nigeria, Qatar and Taiwan) to quantify and characterize the viremic population as well as forecast the changes in the infected population and the corresponding disease burden from 2015 to 2030. Model inputs were agreed upon through expert consensus, and a standardized methodology was followed to allow for comparison across countries. The viremic prevalence is expected to remain constant or decline in all but four countries (Ethiopia, Ghana, Jordan and Oman); however, HCV-related morbidity and mortality will increase in all countries except Qatar and Taiwan. In Qatar, the high-treatment rate will contribute to a reduction in total cases and HCV-related morbidity by 2030. In the remaining countries, however, the current treatment paradigm will be insufficient to achieve large reductions in HCV-related morbidity and mortality.
  9. Chen DS, Hamoudi W, Mustapha B, Layden J, Nersesov A, Reic T, et al.
    J Viral Hepat, 2017 10;24 Suppl 2:44-63.
    PMID: 29105286 DOI: 10.1111/jvh.12759
    The hepatitis C virus (HCV) epidemic was forecasted through 2030 for 17 countries in Africa, Asia, Europe, Latin America and the Middle East, and interventions for achieving the Global Health Sector Strategy on viral hepatitis targets-"WHO Targets" (65% reduction in HCV-related deaths, 90% reduction in new infections and 90% of infections diagnosed by 2030) were considered. Scaling up treatment and diagnosis rates over time would be required to achieve these targets in all but one country, even with the introduction of high SVR therapies. The scenarios developed to achieve the WHO Targets in all countries studied assumed the implementation of national policies to prevent new infections and to diagnose current infections through screening.
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