Displaying publications 1 - 20 of 40 in total

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  1. Thiam Seong Christopher Lim, Tan Yi Jun, Then Ru Fah
    MyJurnal
    Leptospirosis has a wide range of presentation which ranges from mild flu-like symptoms, to severe form including renal failure, liver failure, and hemorrhage. Pulmonary involvement can progress from subtle clinical features to life threatening pulmonary hemorrhage and acute respiratory distress syndrome. Although benefits of corticosteroids in adult respiratory distress syndrome have been proven and accepted, evidence for use of corticosteroids in pulmonary leptospirosis is still limited. Given the vasculitic nature of severe leptospirosis, it has been proposed that addition of intravenous corticosteroid therapy, particularly in cases of pulmonary involvement is beneficial. We report a case of leptospirosis with suspected pulmonary hemorrhage which deteriorates after a few days of admission in our tertiary hospital. We have demonstrated that the prescription of a lower dose of corticosteroid than what was widely reported in the literature can equally led to a satisfactory recovery of the pulmonary hemorrhage.
  2. Fah, Then Ru, Jun, Tan Yi, Lim, Christopher Thiam Seong
    MyJurnal
    Minimal Change Disease (MCD) and Focal Segmental Glomerulosclerosis (FSGS) are common causes of nephrotic syndrome. These two conditions are similar in their presentations but differentiated via their histopathological features and responsiveness to corticosteroids. There are ongoing debates whether MCD and FSGS are at the same spectrum of disease rather than separate entities. FSGS has been postulated to be the severe end of the spectrum of MCD. We have reported a case that has primary FSGS after years of poorly controlled MCD, which supports both conditions are the same spectrum of disease.
  3. Tan, Yi Jun, Then, Ru Fah, Lim, Christopher Thiam Seong
    MyJurnal
    Hepatitis C virus (HCV) infection is known to cause acute and chronic active hepatitis. In addition, HCV also has systemic disorder involvement that links to various extra-hepatic complications. We report a case of a patient which has been diagnosed to have Hepatitis C Genotype 3A who has been started on antiviral. He achieved end treatment response and sustained virologic response. During routine follow up, he experienced acute kidney injury. Renal biopsy showed type III membranoproliferative glomerulonephritis. His proteinuria improved greatly with the addi- tion of angiotensin converting enzyme inhibitor. This case highlights the possibility of appearance of HCV related glomerulonephritis in patient who has sustained virological response.
  4. Tan YJ, Ong SC
    Value Health, 2024 Dec;27(12):1762-1770.
    PMID: 39127252 DOI: 10.1016/j.jval.2024.07.016
    OBJECTIVES: The Assessment of Quality of Life - 6 Dimensions (AQoL-6D), a generic preference-based measure, is an appealing alternative to EQ-5D-5L for assessing health status in patients with chronic heart failure (HF), given its expanded scope. However, without a Malaysian value set, the AQoL-6D cannot generate health state utility values (HSUVs) to support local economic evaluations. This study intended to develop algorithms for predicting EQ-5D-5L HSUVs from AQoL-6D in an HF population.

    METHODS: Cross-sectional data from a multicenter cohort of 419 HF outpatients were used. Both direct and indirect mapping approaches were attempted using 5 sets of explanatory variables and 8 models (ordinary least squares, Tobit, censored least absolute deviations, generalized linear model, 2-part model [TPM], beta regression-based model, adjusted limited dependent variable mixture model, and multinomial ordinal regression [MLOGIT]). The models' predictive performance was assessed through 10-fold cross-validated mean absolute error [MAE] and root mean squared error [RMSE]). Potential prediction bias was also examined graphically. The best-performing models, with the lowest RMSE and no bias, were then identified.

    RESULTS: Among the models evaluated, TPM, which included age, sex, and 5 AQoL-6D dimension scores as predictors, appears to be the best-performing model for directly predicting EQ-5D-5L HSUVs from AQoL-6D. TPM yielded the lowest MAE (0.0802) and RMSE (0.1116), and demonstrated predictive accuracy for HSUVs >0.2 without significant bias. A MLOGIT model developed for response mapping had suboptimal predictive accuracy.

    CONCLUSIONS: This study developed potentially useful mapping algorithms for generating Malaysian EQ-5D-5L HSUVs from AQoL-6D responses among patients with HF when direct EQ-5D-5L data are unavailable.

  5. Ravindran J, Tan YI, Ngeow YF
    Med J Malaysia, 1998 Mar;53(1):16-21.
    PMID: 10968132
    Chlamydia trachomatis is recognized as the most prevalent sexually transmitted organism in many parts of the world. Most complications associated with chlamydial infection in women and their infants can be avoided by appropriate treatment. However, treatment is often not initiated because infections are frequently asymptomatic. The identification of at risk patients and treatment of these patients is a practical clinical approach in the reduction of transmission and prevention of complications. The prevalence of chlamydial infection among patients with pelvic inflammatory disease admitted to Seremban General Hospital was 22.7%. The difference in seropositivity between PID patients (20.5%) and antenatal controls (2.3%) was statistically significant. The corresponding cervical antigen detection rates were 6.8% and 2.3% respectively. Chlamydial infection should be screened for in gynaecological patients and antibiotic policies should take cognizance of the aetiological role played by this organism in pelvic inflammatory disease.
  6. Lee YT, Tan YJ, Oon CE
    Eur J Pharmacol, 2018 Sep 05;834:188-196.
    PMID: 30031797 DOI: 10.1016/j.ejphar.2018.07.034
    Molecular targeted therapies are revolutionized therapeutics which interfere with specific molecules to block cancer growth, progression, and metastasis. Many molecular targeted therapies approved by the Food and Drug Administration (FDA), have demonstrated remarkable clinical success in the treatment of a myriad of cancer types including breast, leukemia, colorectal, lung, and ovarian cancers. This review provides an update on the different types of molecular targeted therapies used in the treatment of cancer, focusing on the fundamentals of molecular targeted therapy, its mode of action in cancer treatment, as well as its advantages and limitations.
  7. Lee YT, Tan YJ, Oon CE
    Acta Pharm Sin B, 2023 Feb;13(2):478-497.
    PMID: 36873180 DOI: 10.1016/j.apsb.2022.09.010
    Cancer is the second leading cause of mortality globally which remains a continuing threat to human health today. Drug insensitivity and resistance are critical hurdles in cancer treatment; therefore, the development of new entities targeting malignant cells is considered a high priority. Targeted therapy is the cornerstone of precision medicine. The synthesis of benzimidazole has garnered the attention of medicinal chemists and biologists due to its remarkable medicinal and pharmacological properties. Benzimidazole has a heterocyclic pharmacophore, which is an essential scaffold in drug and pharmaceutical development. Multiple studies have demonstrated the bioactivities of benzimidazole and its derivatives as potential anticancer therapeutics, either through targeting specific molecules or non-gene-specific strategies. This review provides an update on the mechanism of actions of various benzimidazole derivatives and the structure‒activity relationship from conventional anticancer to precision healthcare and from bench to clinics.
  8. Tan YX, Cheong WL, Fong TS
    Cureus, 2021 Apr 09;13(4):e14388.
    PMID: 33981508 DOI: 10.7759/cureus.14388
    Lower back pain is a common presentation in clinical practice. Although most are musculoskeletal in nature, occult spine infection such as spondylodiscitis is commonly missed due to its insidious onset and non-specific symptoms. We report a case of a 63-year-old diabetic woman who presented to our institution's emergency department with altered mental status, nausea, and vomiting. She had a fall one month prior with persistent lower back-pain of increasing intensity. Initial laboratory data revealed an elevated leukocyte count with neutrophil predominance. Plain radiographs showed extensive gas shadows over the chest wall, abdomen, left thigh, and left knee. CT scan revealed L2 compression fracture with spondylodiscitis at L1/L2, left psoas abscess, and extensive subcutaneous emphysema. Open abscess drainage with extensive wound debridement was performed. Intra-operative pus, as well as blood cultures, yielded Escherichia coli. Unfortunately, the patient succumbed to the infection on the seventh day of admission secondary to multi-organ failure.
  9. Tan YJ, Low JZ, Ong SC
    Clin Ther, 2024 Nov;46(11):e1-e9.
    PMID: 39261261 DOI: 10.1016/j.clinthera.2024.08.008
    PURPOSE: This is a budget impact analysis that compared the scenario of treating heart failure with reduced ejection fraction (HFrEF) using dapagliflozin plus standard of care (SoC) versus a scenario without dapagliflozin, from the perspective of Ministry of Health (MOH) Malaysia over a 5-year time horizon.

    METHODS: A Microsoft Excel-based cost calculator was developed for such comparison. The estimated size of eligible population, uptake rates for dapagliflozin, as well as costs related to drugs, clinical events, and adverse events were based on published data, official tariffs, and databases, and expert opinion. Clinical data from the DAPA-HF trial were used to inform efficacy and safety inputs (i.e., hospitalization for heart failure (hHF), cardiovascular death, and adverse events). Results were reported as total annual and cumulative costs (in 2023 Malaysian Ringgits [RM], United States Dollars [USD], and European Union Euros, [EUR]; with exchange rates of 1 USD = RM 4.40 and 1 EUR = RM 4.90]), as well as the number of clinical events. Sensitivity and scenario analyses were also conducted.

    FINDINGS: The base-case analysis estimated that over a five-year period, the adoption of dapagliflozin for HFrEF treatment would result in a cumulative cost-saving of RM 2.6 million (USD 0.6 million/EUR 0.5 million), representing a 0.3% reduction in costs, driven primarily by reduced expenditure on hHF. Moreover, dapagliflozin treatment would lead to 731 fewer hHF and 366 fewer cardiovascular deaths. Sensitivity and scenario analyses revealed that the results were most sensitive to assumptions regarding loop diuretic requirements and the cost of dapagliflozin. Although cost savings or a net-zero balance were projected for the first four years, an anticipated 2.5% annual increase in dapagliflozin uptake in the longer term would lead to additional costs for the MOH, starting from the fifth year.

    IMPLICATIONS: Incorporating dapagliflozin into the SoC can improve health outcomes for HFrEF patients and may generate cost savings, potentially easing the economic strain of HFrEF management on Malaysia's public healthcare system in the short term. Nonetheless, a modest increase in budget should be anticipated as more patients gain access to the treatment over time.

  10. Tan YJ, Ong SC, Kan YM
    Appl Health Econ Health Policy, 2023 Nov;21(6):857-875.
    PMID: 37646915 DOI: 10.1007/s40258-023-00825-5
    OBJECTIVE: This systematic review aimed to summarise the outcomes of economic evaluations that evaluated sodium-glucose cotransporter-2 inhibitors (SGLT2i) in combination with standard of care compared to standard of care alone for patients with chronic heart failure.

    METHODS: This systematic review searched MEDLINE, CINAHL+, Econlit, Scopus, the Cochrane Library, the National Health Service Economic Evaluation Database and the Cost-Effectiveness Analysis Registry from inception to 31 December, 2022, for relevant economic evaluations, which were critically appraised using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) and Bias in Economic Evaluation (ECOBIAS) criteria. The costs, quality-adjusted life-years, incremental cost-effectiveness ratios and cost-effectiveness thresholds were qualitatively analysed. Net monetary benefits at different decision thresholds were also computed. Subgroup analyses addressing the heterogeneity of economic outcomes were conducted. All costs were adjusted to 2023 international dollar (US$) values using the CCEMG-EPPI-Centre cost converter.

    RESULTS: Thirty-nine economic evaluations that evaluated dapagliflozin and empagliflozin in patients with heart failure were found: 32 for the left ventricular ejection fraction (LVEF) ≤ 40% and seven for LVEF > 40%. Sodium-glucose cotransporter-2 inhibitors were cost-effective in all but two economic evaluations for LVEF > 40%. Economic outcomes varied widely, but favoured SGLT2i use in LVEF ≤ 40% over LVEF > 40% and upper-middle income over high-income countries. At a threshold of US$30,000/quality-adjusted life-year, ~ 90% of high to upper-middle income countries would consider SGLT2i cost-effective for heart failure treatment. The generalisability of study findings to low- and low-middle income countries is limited because of insufficient evidence.

    CONCLUSIONS: Using SGLT2i to treat heart failure is cost-effective, with more certainty in LVEF ≤ 40% compared to LVEF > 40%. Policymakers in jurisdictions where economic evaluations are not available could potentially use this study's findings to make informed decisions about treatment adoption.

    SYSTEMATIC REVIEW PROTOCOL REGISTRATION: This study protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO; CRD42023388701).

  11. Lee YT, Tan YJ, Oon CE
    Biomedicines, 2023 Nov 15;11(11).
    PMID: 38002059 DOI: 10.3390/biomedicines11113059
    Growing evidence has highlighted that mitochondrial dysfunction contributes to drug-induced toxicities and leads to drug attrition and post-market withdrawals. The acetylation or deacetylation of mitochondrial proteins can affect mitochondrial functions as the cells adapt to various cellular stresses and other metabolic challenges. SIRTs act as critical deacetylases in modulating mitochondrial function in response to drug toxicity, oxidative stress, reactive oxygen species (ROS), and energy metabolism. We previously showed that a recently characterised SIRT inhibitor (BZD9L1) is non-toxic in rodents in a short-term toxicity evaluation. However, the impact of BZD9L1 on mitochondrial function is unknown. This work aims to determine the effects of BZD9L1 on mitochondrial function in human normal liver and kidney-derived cell lines using the Agilent Seahorse Cell Mito Stress Test to complement our short-term toxicity evaluations in vivo. The Mito Stress assay revealed that BZD9L1 could potentially trigger oxidative stress by inducing ROS, which promotes proton leak and reduces coupling efficiency in liver-derived THLE cells. However, the same was not observed in human kidney-derived HEK293 cells. Interestingly, BZD9L1 had no impact on SIRT3 protein expression in both cell lines but affected SOD2 and its acetylated form at 72 h in THLE cells, indicating that BZD9L1 exerted its effect through SIRT3 activity rather than protein expression. In contrast, BZD9L1 reduced SIRT1 protein expression and impacted the p53 protein differently in both cell lines. Although BZD9L1 did not affect the spare respiratory capacity in vitro, these findings call for further validation of mitochondrial function through assessment of other mitochondrial parameters to evaluate the safety of BZD9L1.
  12. Tan YJ, Linden S, Ong SC
    PLoS One, 2024;19(8):e0305257.
    PMID: 39178204 DOI: 10.1371/journal.pone.0305257
    INTRODUCTION: Empagliflozin demonstrates promising clinical benefits in patients with heart failure (HF). While an early study demonstrates that empagliflozin is cost-effective for treating HF patients with reduced ejection fraction (HFrEF) in Malaysia, its cost-effectiveness for HF with ejection fraction (EF)>40% remains unclear. Therefore, the current study aimed to assess the cost-effectiveness of adding empagliflozin to the standard of care (SoC) for HF patients with EF>40% from the perspective of Malaysian healthcare system. Subsequently, the results were consolidated with the findings for HFrEF to evaluate the cost-effectiveness of empagliflozin when used for all HF patients in Malaysia, irrespective of EF.

    METHODS: A cost-utility analysis was performed using a validated Markov model, which modelled a cohort of adult patients through health states related to symptom severity and functional impairment, to estimate costs and quality-adjusted life-years (QALYs). The influence of model inputs and assumptions, sensitivity, scenario, and subgroup analyses were explored. All costs were expressed in 2022 Malaysian ringgits (RM). Costs and QALYs were discounted at an annual rate of 3.0% as per local pharmacoeconomic guideline.

    RESULTS: The base-case incremental cost-effectiveness ratio (ICER) for HF patients with EF>40% was RM 40,454 per QALY gained. At a cost-effectiveness threshold of RM 47,439/QALY gained, empagliflozin was cost-effective in 57% of replications. The model outcomes were sensitive to inputs related to the treatment effect of empagliflozin in reducing HF-related hospitalisation and cardiovascular mortality, and empagliflozin cost. For the overall HF population, the ICER was RM 29,463/QALY gained.

    CONCLUSION: The findings suggest that empagliflozin is a cost-effective treatment option for the Malaysian HF population, including those with EF>40%. As such, the intervention warrants consideration by the Malaysian healthcare provider to mitigate the burden of HF and address the unmet needs of the EF>40% population.

  13. Wong LP, Alias H, Tan YR, Tan KM
    PMID: 34846801 DOI: 10.1111/opn.12436
    BACKGROUND: COVID-19 is a threat to everyone's health and can be especially devastating to older individuals.

    AIM: This study examined the behavioural prevention practices against SARS-CoV-2 infection and the intention to vaccinate among older people when the COVID-19 vaccine is on the verge of becoming available.

    METHOD: A cross-sectional, online survey was conducted between 14th July and 8th October 2020 among the older people in Malaysia. A questionnaire was designed to assess the practice towards measures preventing SARS-CoV-2 infection, and COVID-19 vaccination attitudes and intention. Socio-demographic characteristics, constructs of a health belief model (HBM), the 6-item state version of the State-Trait Anxiety Inventory (STAI-6) were correlates of the main outcomes.

    FINDINGS: The mean score of total preventive measures scores was 13.4 ± 1.7 out of a maximum score of 15, indicating very good prevention practices. By demographics, females, having a tertiary education exhibited higher prevention practices in the univariable analyses. Components of the HBM and being female remain significant correlates of higher prevention practices in multivariable logistic regression analysis (MLRA). A total of 657 (87.1%) participants responded and intend to receive the COVID-19 vaccination. Provider recommendations may improve vaccination uptake (91.6%). MLRA revealed that having a positive vaccination attitude was 16 times more likely to accept the COVID-19 vaccination (OR = 16.10; 95% CI 8.97-28.91). Hearing of someone they know who has COVID-19 serves as a cue to action and significantly influences vaccination (OR = 4.25; 95% CI 1.80-10.03). Participants below 70 years old expressed higher vaccination intention (OR = 2.07; 95% CI 1.19-3.58).

    CONCLUSION: The results provide the first evidence for public authorities to target older people vulnerable to compliance with recommended preventive measures against SARS-CoV-2 infections.

  14. Tan YJ, Lee YT, Mancera RL, Oon CE
    Life Sci, 2021 Nov 01;284:119747.
    PMID: 34171380 DOI: 10.1016/j.lfs.2021.119747
    BZD9L1 was previously described as a SIRT1/2 inhibitor with anti-cancer activities in colorectal cancer (CRC), either as a standalone chemotherapy or in combination with 5-fluorouracil. BZD9L1 was reported to induce apoptosis in CRC cells; however, the network of intracellular pathways and crosstalk between molecular players mediated by BZD9L1 is not fully understood. This study aimed to uncover the mechanisms involved in BZD9L1-mediated cytotoxicity based on previous and new findings for the prediction and identification of related pathways and key molecular players. BZD9L1-regulated candidate targets (RCTs) were identified using a range of molecular, cell-based and biochemical techniques on the HCT 116 cell line. BZD9L1 regulated major cancer pathways including Notch, p53, cell cycle, NFκB, Myc/MAX, and MAPK/ERK signalling pathways. BZD9L1 also induced reactive oxygen species (ROS), regulated apoptosis-related proteins, and altered cell polarity and adhesion profiles. In silico analyses revealed that most RCTs were interconnected, and were involved in the modulation of catalytic activity, metabolism and transcription regulation, response to cytokines, and apoptosis signalling pathways. These RCTs were implicated in p53-dependent apoptosis pathway. This study provides the first assessment of possible associations of molecular players underlying the cytotoxic activity of BZD9L1, and establishes the links between RCTs and apoptosis through the p53 pathway.
  15. Tee SW, Richards A, Tan YH, Jeyabalan D, Durairaj G
    J Surg Case Rep, 2022 Dec;2022(12):rjac585.
    PMID: 36578629 DOI: 10.1093/jscr/rjac585
    Desmoid fibromatosis is a rare, benign, locally aggressive fibroblastic proliferation that may occur in almost any anatomical location. Due to its rarity and unpredictable clinical course, there has not been a standard guideline of treatment. We encountered a case of desmoid fibromatosis in our centre. A young lady previously fit and well was referred for a symptomatic, rapidly growing left sided abdominal mass. Otherwise, she denied any bowel related symptoms or constitutional manifestation. Imaging demonstrated a large well-defined lobulated solid-cystic mass extending from vertebral level T10 to L5, measuring 10.5 cm × 15 cm × 23 cm. The mass was in close proximity with the left adrenal gland, left kidney, pancreas and spleen. Ultrasound guided biopsy interpreted it as a fibroblastic or myelofibroblastic tumour, favouring desmoid fibromatosis. Surgery was then performed where the mass was removed along with the left adrenal gland and kidney. Post-operative care was complicated with pulmonary embolism, hospital-acquired pneumonia and pancreatitis.
  16. Abdalla MMI, Azzani M, Rajendren R, Hong TK, Balachandran Y, Hassan TR, et al.
    Am J Med Sci, 2021 Oct 01.
    PMID: 34606752 DOI: 10.1016/j.amjms.2021.07.015
    BACKGROUND: Traditional teaching methods via faculty lectures and text-based materials lack interactivity. Hence, this research aimed to compare the effectiveness of story-based audiovisual mnemonics and the conventional text-reading method on medical students' memory consolidation.

    METHODS: A single-center, systematically randomly sampled, single-blinded, controlled study was conducted among 80 first-year medical students. The students were randomly assigned to the text-reading (control) or story-based audiovisual mnemonics (intervention) group. After completing the learning session, the participants immediately took a test that consisted of ten multiple-choice questions, each of which had one correct single-response answer, and an oral recall test that consisted of ten keywords based on the given topics. The test was repeated at 1 week, 2 weeks, and 4 weeks post intervention. Descriptive and inferential statistics were utilized to assess the participants' responses. The mean score difference between the audiovisual mnemonics and control groups was determined by using a two-tailed unpaired t-test.

    RESULTS: The participants in the intervention group had statistically significant higher marks in the multiple-choice test as compared to the participants in the control group. The intervention group also spent a statistically significant shorter time to recall keywords in the oral recall test in comparison to the control group.

    CONCLUSION: The story-based audiovisual mnemonics method is more effective than the conventional text-reading method in promoting memory retention among medical students.

  17. Tan YJ, Tan YS, Yeo CI, Chew J, Tiekink ERT
    J Inorg Biochem, 2019 03;192:107-118.
    PMID: 30640150 DOI: 10.1016/j.jinorgbio.2018.12.017
    Four binuclear phosphanesilver(I) dithiocarbamates, {cyclohexyl3PAg(S2CNRR')}2 for R = R' = Et (1), CH2CH2 (2), CH2CH2OH (3) and R = Me, R' = CH2CH2OH (4) have been synthesised and characterised by spectroscopy and crystallography, and feature tri-connective, μ2-bridging dithiocarbamate ligands and distorted tetrahedral geometries based on PS3 donor sets. The compounds were evaluated for anti-bacterial activity against a total of 12 clinically important pathogens. Based on minimum inhibitory concentration (MIC) and cell viability tests (human embryonic kidney cells, HEK 293), 1-4 are specifically active against Gram-positive bacteria while demonstrating low toxicity; 3 and 4 are active against methicillin resistant S. aureus (MRSA). Across the series, 4 was most effective and was more active than the standard anti-biotic chloramphenicol. Time kill assays reveal 1-4 to exhibit both time- and concentration-dependent pharmacokinetics against susceptible bacteria. Compound 4 demonstrates rapid (within 2 h) bactericidal activity at 1 and 2 × MIC to reach a maximum decrease of 5.2 log10 CFU/mL against S. aureus (MRSA).
  18. Tan YJ, Yeo CI, Halcovitch NR, Jotani MM, Tiekink ERT
    Acta Crystallogr E Crystallogr Commun, 2017 Apr 01;73(Pt 4):493-499.
    PMID: 28435705 DOI: 10.1107/S205698901700353X
    The title compound, (C6H11)3PS (systematic name: tri-cyclo-hexyl-λ(5)-phosphane-thione), is a triclinic (P-1, Z' = 1) polymorph of the previously reported ortho-rhom-bic form (Pnma, Z' = 1/2) [Kerr et al. (1977 ▸). Can. J. Chem. 55, 3081-3085; Reibenspies et al. (1996 ▸). Z. Kristallogr. 211, 400]. While conformational differences exist between the non-symmetric mol-ecule in the triclinic polymorph, cf. the mirror-symmetric mol-ecule in the ortho-rhom-bic form, these differences are not chemically significant. The major feature of the mol-ecular packing in the triclinic polymorph is the formation of linear chains along the a axis sustained by methine-C-H⋯S(thione) inter-actions. The chains pack with no directional inter-actions between them. The analysis of the Hirshfeld surface for both polymorphs indicates a high degree of similarity, being dominated by H⋯H (ca 90%) and S⋯H/H⋯S contacts.
  19. Tan YZ, Chong YQ, Khong E, Liew YK, Chieng N
    Int J Pharm, 2019 Jul 20;566:400-409.
    PMID: 31136777 DOI: 10.1016/j.ijpharm.2019.05.063
    Live attenuated Mycobacterium bovis (M. bovis), marketed as Bacille Calmette-Guérin is the only FDA-approved vaccine against tuberculosis. The prerequisite of cold chain storage between 2 and 8 °C hinders the global vaccination effort. The study aims to investigate the effect of trehalose, sucrose and glycerol combinations in enhancing the stability of M. bovis. The bacilli were formulated in various ratios of trehalose-glycerol, sucrose-glycerol, trehalose-sucrose-glycerol systems (test samples) and sodium glutamate (control), freeze-dried and stored for 28 days at 4 °C, 25 °C and 37 °C. Bacteria viability at pre-, post-freeze-drying and after storage were quantified by its density in colony-forming unit per milliliter (CFU/mL) as obtained through the pour plate method. Formulations were characterized using differential scanning calorimetry. Structural collapsed cakes were found on all freeze-dried formulations because of the low Tg'. Comparing between binary and ternary formulations, trehalose-sucrose-glycerol was found to be a superior lyoprotectant. Upon storage, the viability of bacteria in disaccharide-polyol formulations was highest when stored at 4 °C followed by 25 °C. The lowest viability was found after storage at 37 °C. While the ternary disaccharide-polyol system may be used as a thermoprotectant up to 25 °C, sodium glutamate has a superior thermoprotective effect at temperature above 25 °C.
  20. Tan YJ, Lee YT, Yeong KY, Petersen SH, Kono K, Tan SC, et al.
    Future Med Chem, 2018 Sep 01;10(17):2039-2057.
    PMID: 30066578 DOI: 10.4155/fmc-2018-0052
    AIM: This study aims to investigate the mode of action of a novel sirtuin inhibitor (BZD9L1) and its associated molecular pathways in colorectal cancer (CRC) cells.

    MATERIALS & METHODS: BZD9L1 was tested against metastatic CRC cell lines to evaluate cytotoxicity, cell cycle and apoptosis, senescence, apoptosis related genes and protein expressions, as well as effect against major cancer signaling pathways.

    RESULTS & CONCLUSION: BZD9L1 reduced the viability, cell migration and colony forming ability of both HCT 116 and HT-29 metastatic CRC cell lines through apoptosis. BZD9L1 regulated major cancer pathways differently in CRC with different mutation profiles. BZD9L1 exhibited anticancer activities as a cytotoxic drug in CRC and as a promising therapeutic strategy in CRC treatment.

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