Displaying publications 1 - 20 of 146 in total

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  1. Lee FK, Chan NJ, Krishnan P, Datu Abdul Salam DS, Chee XW, Muhamad A, et al.
    J Nat Prod, 2024 Mar 05.
    PMID: 38442031 DOI: 10.1021/acs.jnatprod.3c00707
    Schwarzinicines A-D, a series of alkaloids recently discovered from Ficus schwarzii, exhibit pronounced vasorelaxant activity in rat isolated aorta. Building on this finding, a concise synthesis of schwarzinicines A and B has been reported, allowing further investigations into their biological properties. Herein, a preliminary exploration of the chemical space surrounding the structure of schwarzinicine A (1) was carried out aiming to identify structural features that are essential for vasorelaxant activity. A total of 57 analogs were synthesized and tested for vasorelaxant activity in rat isolated aorta. Both efficacy (Emax) and potency (EC50) of these analogs were compared. In addition to identifying structural features that are required for activity or associated with potency enhancement effect, four analogs showed significant potency improvements of up to 40.2-fold when compared to 1. Molecular dynamics simulation of a tetrameric 44-bound transient receptor potential canonical-6 (TRPC6) protein indicated that 44 could potentially form important interactions with the residues Glu509, Asp530, Lys748, Arg758, and Tyr521. These results may serve as a foundation for guiding further structural optimization of the schwarzinicine A scaffold, aiming to discover even more potent analogs.
  2. Tan YS, Ng MP, Tan CH, Tang WK, Sim KS, Yong KT, et al.
    J Nat Prod, 2024 Feb 23;87(2):286-296.
    PMID: 38284153 DOI: 10.1021/acs.jnatprod.3c00960
    Nine new alkaloids, eugeniinalines A-H (1-8) and (+)-eburnamenine N-oxide (9), comprising one quinoline, six indole, and two isogranatanine alkaloids, were isolated from the stem-bark extract of the Malayan Leuconotis eugeniifolia. The structures and absolute configurations of these alkaloids were established based on the analysis of the spectroscopic data, GIAO NMR calculations, DP4+ probability analysis, TDDFT-ECD method, and X-ray diffraction analysis. Eugeniinaline A (1) represents a new pentacyclic quinoline alkaloid with a 6/6/5/6/7 ring system. Eugeniinaline G (7) and its seco-derivative, eugeniinaline H (8), were the first isogranatanine alkaloids isolated as natural products. The known alkaloids leucolusine (10) and melokhanine A (11) were found to be the same compound, based on comparison of the spectroscopic data of both compounds, with the absolute configuration of (7R, 20R, 21S). Eugeniinalines A and G (1 and 7) showed cytotoxic activity against the HT-29 cancer cell line with IC50 values of 7.1 and 7.2 μM, respectively.
  3. Abuzaid H, Abdelrazig S, Ferreira L, Collins HM, Kim DH, Lim KH, et al.
    ACS Omega, 2024 Jan 09;9(1):2012.
    PMID: 38222495 DOI: 10.1021/acsomega.3c09291
    [This corrects the article DOI: 10.1021/acsomega.2c00997.].
  4. Lim KH, Cheong YL, Lim HL, Cheong KC, Hashim MHM, Marine AA, et al.
    Tob Induc Dis, 2024;22.
    PMID: 38268983 DOI: 10.18332/tid/176164
    INTRODUCTION: Perception is an essential factor influencing smoking among adolescents. Thus, a valid tool for measuring perception is a requisite in smoking studies. This study further establishes the validity and reliability of a Malay language version of the Perception Towards Smoking Questionnaire (BM-PTSQ) for assessing the perception of smoking among secondary school-going adolescents in Malaysia.

    METHODS: We administered the BM-PTSQ to 669 secondary school students selected through multistage sampling; 60% of respondents were male (n=398), and 69.9% (n=463) were from rural areas. Respondents were aged 13-16 years, 36.4% (n=241) were 13 years, 40.0% (n=265) were 14 years, and 23.6% (n=156) were 16 years old. We used parallel and exploratory factor analysis (EFA) to determine the domains of the questionnaire. In addition, we also employed EFA, confirmatory factor analyses (CFA), and Cronbach's alpha to evaluate the construct validity and reliability of the BM-PTSQ.

    RESULTS: EFA and parallel analysis identified two domains in the BM-PTSQ that accounted for 62.9% of the observed variance, and CFA confirmed the two-domain structure. The two domains' internal consistency scores ranged from 0.702 to 0.80, which suggested adequate reliability.

    CONCLUSIONS: The BM-PTSQ has acceptable psychometric validity and is appropriate for assessing smoking perception and intention among Malaysian secondary school-aged youth. Researchers should further evaluate this tool's applicability in a more sociodemographically diverse population.

  5. Chu JN, Krishnan P, Lim KH
    Nat Prod Bioprospect, 2023 Nov 27;13(1):53.
    PMID: 38010490 DOI: 10.1007/s13659-023-00418-8
    Sarcandra glabra (Thunb.) Nakai is a perennial evergreen herb categorised within the Sarcandra Gardner genus under the Chloranthaceae family. Indigenous to tropical and subtropical regions of East Asia and India, this species is extensively distributed across China, particularly in the southern regions (Sichuan, Yunnan, and Jiangxi). In addition to its high ornamental value, S. glabra has a rich history of use in traditional Chinese medicine, evident through its empirical prescriptions for various ailments like pneumonia, dysentery, fractures, bruises, numbness, amenorrhea, rheumatism, and other diseases. Besides, modern pharmacological studies have revealed various biological activities, such as antitumour, anti-bacterial, anti-viral anti-inflammatory and immunomodulatory effects. The diverse chemical constituents of S. glabra have fascinated natural product researchers since the 1900s. To date, over 400 compounds including terpenoids, coumarins, lignans, flavonoids, sterols, anthraquinones, organic acids, and organic esters have been isolated and characterised, some featuring unprecedented structures. This review comprehensively examines the current understanding of S. glabra's phytochemistry and pharmacology, with emphasis on the chemistry and biosynthesis of its unique chemotaxonomic marker, the lindenane-type sesquiterpenoids.
  6. Cheah YK, Zainuddin NH, Kee CC, Lim KH, Omar MA, Cheong YL
    Clin Child Psychol Psychiatry, 2023 Oct;28(4):1341-1357.
    PMID: 36428238 DOI: 10.1177/13591045221142497
    Sexual behaviour and mental health among adolescents are major public health issues. This study examines how lifestyles affect sexual behaviour among school-going adolescents in Malaysia, and the potential mediational role of mental health. It is the first to our knowledge to explore the mediating effect of mental health on sexual behaviour with a focus on a fast-growing developing country. Data were obtained from the National Health and Morbidity Survey 2017 (n = 27,497). Structural equation modelling was utilized to examine depression and anxiety as mediators of the relationships between sexual behaviour and smoking, alcohol drinking and illicit drug use, controlling for sociodemographic factors. Results showed that adolescents who smoked, consumed alcohol, used illicit drugs, and had depression and anxiety were more likely to engage in sexual behaviour than others. Depression and anxiety partially mediated the relationships between sexual behaviour and smoking, and illicit drug use. The association between alcohol drinking and sexual behaviour was fully mediated by depression and anxiety. In conclusion, lifestyles may affect sexual behaviour through mediation of mental health. Therefore, policymakers should take mental health factors into consideration when designing adolescent sexual behaviour preventative interventions.
  7. Teh CH, Rampal S, Lim KH, Azahadi O, Tahir A
    Nicotine Tob Res, 2023 Jun 09;25(7):1340-1347.
    PMID: 36879440 DOI: 10.1093/ntr/ntad035
    INTRODUCTION: Tobacco use is one of the major preventable risk factors for premature death and disability worldwide. Understanding the trend of tobacco use over time is important for informed policy making.

    AIMS AND METHODS: The present study aimed to examine the changes in mean daily cigarette consumption among random samples of the Malaysian current smoker population over 20 years using an age-period-cohort (APC) approach. We conducted APC analysis using a multilevel hierarchical age-period-cohort model and data from four nationally representative, repeated cross-sectional surveys (National Health and Morbidity Survey) conducted in 1996, 2006, 2011, and 2015 among individuals aged 18 to 80 years. Analyses were also stratified by gender and ethnicity.

    RESULTS: Overall, mean daily cigarette consumption (smoking intensity) among current smokers increased with age until 60, after which a drop was observed. There were increases in daily cigarette consumption across birth cohorts. Age and cohort trends did not vary by gender but by ethnicity. The decreasing cigarette consumption after age 60 among the current smoker population was consistent with those observed among the Chinese and Indians, a trend that was not observed in Malays and other aborigines. In contrast, the increasing cohort trend was consistent with those observed among the Malays and other bumiputras.

    CONCLUSIONS: The present study highlighted important ethnic-specific trends for mean daily cigarette consumption among the current smoker population in Malaysia. These findings are essential in guiding the formulation of interventional strategies or implementation of national tobacco control policies and help achieve the Ministry of Health Malaysia's 2025 and 2045 targets for smoking prevalence.

    IMPLICATIONS: This is the first APC study on smoking intensity among current smokers in a multiracial, middle-income nation. Very few studies had performed gender- and ethnic-stratified APC analyses. The ethnic-stratified APC analyses provide useful insights into the overall age and cohort trends observed among the current smoker population in Malaysia. Therefore, the present study could add evidence to the existing literature on the APC trends of smoking intensity. The APC trends are also important in guiding the government to develop, implement, and evaluate antismoking strategies.

  8. Cheah JSS, Lim KH
    Eur Manag J, 2023 Apr 08.
    PMID: 37362857 DOI: 10.1016/j.emj.2023.04.003
    The outbreak of the COVID-19 pandemic has dramatically changed human lifestyles and contributed to the creation of a new normal in the business environment. This study examines the direct and indirect impacts of internal and external corporate social responsibility (CSR) practices on employee job satisfaction through organisational identification, conditional on employee age. A total of 236 valid responses were received from eight multinational medical device manufacturers in Malaysia. Partial least squares and PROCESS algorithms were employed to assess the hypothesised interactions between the predictors and criterion variables. The empirical results showed that internal CSR (i.e., CSR to employee) could significantly drive a greater sense of belonging and work satisfaction. Surprisingly, however, external CSR (i.e., CSR to community) negatively affects job fulfilment in the medical devices industry during the pandemic. Nevertheless, the findings also showed that ongoing CSR activities in the community could build organisational identification and subsequently improve job satisfaction. Conversely, CSR to environment did not statistically influence job satisfaction, either directly or indirectly. The mediating effects of organisational identification were not associated with employee age. This study provides a practical framework for effective CSR strategies amid the pandemic that can help organisations align with social responsibility, enhance their reputation, and contribute to society.
  9. Tang SY, Tan CH, Sim KS, Yong KT, Lim KH, Low YY, et al.
    Phytochemistry, 2023 Apr;208:113587.
    PMID: 36646163 DOI: 10.1016/j.phytochem.2023.113587
    Eight undescribed iboga alkaloids, polyneurines A-H, were isolated from the bark of Tabernaemontana polyneura. The structures of these alkaloids were established by interpretation of the MS and NMR data, while the configurations were determined using GIAO NMR calculations and DP4+ probability analysis, TDDFT-ECD method, or X-ray diffraction analysis. Polyneurine A possesses a γ-lactone unit embedded within the iboga skeleton, while polyneurines D and E incorporate a formylmethyl moiety at C-3 of the iboga skeleton. Biosynthetic pathways towards the formation of polyneurines A, C, D, and E were proposed.
  10. Tan YS, Wong SK, Yong KT, Lim KH, Lim SH, Low YY
    J Nat Prod, 2023 Jan 27;86(1):232-236.
    PMID: 36651825 DOI: 10.1021/acs.jnatprod.2c00731
    Eugeniifoline (1), a pentacyclic indole alkaloid with a five-membered ring E, was isolated for the first time as a natural product from the stem-bark extract of Leuconotis eugeniifolia. Eugeniifoline (1) was previously reported as a synthetic product from a diversity-enhanced extract, but with the configuration at C-21 reported as S (1a). The configuration at C-21 was revised to R as shown in 1, based on the NOE data, GIAO NMR calculations, and DP4+ probability analysis, as well as the TDDFT-ECD method.
  11. Lim KH, Yun YX, Cheong YL, Sulaiman N, Mahadzir ME, Lim JH, et al.
    Tob Induc Dis, 2023;21:36.
    PMID: 36909814 DOI: 10.18332/tid/159624
    INTRODUCTION: The Fagerström test for nicotine dependence (FTND) was forward-backwards translated into the Malay language (FTND-M) and administered to 152 daily smokers who sought treatment for smoking cessation in government health clinics in Selangor state, Malaysia.

    METHODS: Using confirmatory factor analysis (CFA), four measurement models with the best relative fit were compared, one uni-dimensional model, and three different two-domain (morning and daytime smoking) models.

    RESULTS: The findings indicate that the best model of the FTND-M was a two-domain model, wherein domain one represented morning smoking (time to first cigarette of the day, smoking more in the morning, and which cigarette would you hate to give up) and domain two represented daytime smoking (cigarettes per day, difficulty refraining from smoking, and smoking when ill) which showed good model fit [χ2/df=1.932, goodness of fit (GFI) of 0.967, comparative fix index (CFI) of 0.945, incremental fit index (IFI) of 0.98, Tucker-Lewis index (TLI) of 0.95 and a real mean square end of approximation (RMSEA) of 0.079, and substantial reliability >0.70].

    CONCLUSIONS: This study indicates that the FTND-M can be used to assess these two dimensions of nicotine addiction among daily smokers in a clinical setting.

  12. Abuzaid H, Abdelrazig S, Ferreira L, Collins HM, Kim DH, Lim KH, et al.
    ACS Omega, 2022 Jun 28;7(25):21473-21482.
    PMID: 35785302 DOI: 10.1021/acsomega.2c00997
    The O-acetyl (or acetate) derivative of the Aspidosperma alkaloid Jerantinine A (JAa) elicits anti-tumor activity against cancer cell lines including mammary carcinoma cell lines irrespective of receptor status (0.14 < GI50 < 0.38 μM), targeting microtubule dynamics. By exploiting breast cancer cells' upregulated transferrin receptor 1 (TfR1) expression and apoferritin (AFt) recognition, we sought to develop an AFt JAa-delivery vehicle to enhance tumor-targeting and reduce systemic toxicity. Optimizing pH-mediated reassembly, ∼120 JAa molecules were entrapped within AFt. Western blot and flow cytometry demonstrate TfR1 expression in cancer cells. Enhanced internalization of 5-carboxyfluorescein-conjugated human AFt in SKBR3 and MDA-MB-231 cancer cells is observed compared to MRC5 fibroblasts. Accordingly, AFt-JAa delivers significantly greater intracellular JAa levels to SKBR3 and MDA-MB-231 cells than naked JAa (0.2 μM) treatment alone. Compared to naked JAa (0.2 μM), AFt-JAa achieves enhanced growth inhibition (2.5-14-fold; <0.02 μM < GI50 < 0.15 μM) in breast cancer cells; AFt-JAa treatment results in significantly reduced clonal survival, more profound cell cycle perturbation including G2/M arrest, greater reduction in cell numbers, and increased apoptosis compared to the naked agent (p < 0.01). Decreased PLK1 and Mcl-1 expression, together with the appearance of cleaved poly (ADP-ribose)-polymerase, corroborate the augmented potency of AFt-JAa. Hence, we demonstrate that AFt represents a biocompatible vehicle for targeted delivery of JAa, offering potential to minimize toxicity and enhance JAa activity in TfR1-expressing tumors.
  13. Cheah YK, Syed Anera SN, Kee CC, Lim KH, Omar MA
    Hypertens Res, 2022 Feb 16.
    PMID: 35173284 DOI: 10.1038/s41440-022-00858-8
    The prevalence of high sodium-related diseases is increasing across the globe. Knowledge plays an important role in disease prevention. The objective of the present study was to examine sociodemographic factors associated with knowledge of high sodium-related diseases. The Malaysian Community Salt Survey (MyCoSS) was used in the present study for secondary analyses. It is a nationwide cross-sectional survey that was conducted in Malaysia. A non-parametric test to evaluate trends and a negative binomial regression were utilised to assess knowledge of high sodium-related diseases. Income, educational level, gender, ethnicity, house locality and hypertension were found to be significantly associated with knowledge of high sodium-related diseases. In particular, higher income earners, well-educated people, women, Malays, urban dwellers and hypertensive adults were more likely to have acquired a lot of knowledge of high sodium-related diseases compared to that acquired by lower income earners, less-educated people, men, individuals of other ethnic groups, rural dwellers and nonhypertensive adults. In conclusion, sociodemographic factors and hypertension play an important role in knowledge acquired about high sodium-related diseases. The findings of the present study could inform a future policy directed towards increasing knowledge about high sodium-related diseases among the population in Malaysia.
  14. Jane Ling MY, Ahmad N, Mohd Yusoff MF, Lim KH
    PLoS One, 2022;17(1):e0263355.
    PMID: 35100321 DOI: 10.1371/journal.pone.0263355
    BACKGROUND: Adolescent e-cigarette use has increased dramatically. Most e-cigarette liquids contain nicotine, which can harm the developing adolescent brain. Local studies examining the risk factors of adolescent e-cigarette use and interactions between its risk factors are limited. This study was aimed at determining the prevalence of current e-cigarette use and its associated factors among in-school adolescents in West Malaysia. We also examined the possible sociodemographic characteristic, lifestyle risk behaviour and parental factor interactions that affect the probability of current e-cigarette use.

    METHODS: We conducted a cross-sectional study using data from the National Health and Morbidity Survey 2017. Respondents aged 13-18 years were included in the study. The data were analysed using STATA (v.15).

    RESULTS: The prevalence of current e-cigarette use was 9.1%. Male gender, older age, Malay ethnicity, schooling in urban area, current smoking, current alcohol use, current drug use, having parents that are not married and living together and parental tobacco product use were significantly associated with current e-cigarette use. There were significant interactions between: i) gender with age, ethnicity, current smoking, current alcohol use and current drug use, ii) ethnicity with current smoking and current alcohol use, iii) locality with ethnicity, current smoking and current alcohol use, iv) current drug use with age, ethnicity, current smoking and current alcohol use, v) parental marital status with gender, age and ethnicity, and vi) parental tobacco use with ethnicity and current smoking.

    CONCLUSION: Our findings identify significant associations between sociodemographic characteristics, lifestyle risk behaviours and parental factors with current e-cigarette use. They also provide new insight into the interactions between these factors that affect the probability of current e-cigarette use among West Malaysian adolescents. Efforts to tackle e-cigarette use in Malaysian adolescents should target sociodemographic characteristics, lifestyle risk behaviours and parental factors such as smoking cessation intervention for parents.
  15. Booi HN, Lee MK, Fung SY, Ng ST, Tan CS, Lim KH, et al.
    Int J Med Mushrooms, 2022;24(10):1-14.
    PMID: 36374826 DOI: 10.1615/IntJMedMushrooms.2022045068
    COVID-19 infection has been a key threat to the public health system globally, with an estimated 248 million cases worldwide. COVID-19 patients are subject to a higher risk of developing chronic respiratory disorders that are closely associated with long-term disability, multi-morbidity, and premature mortality. Although there have been recent advancements in respiratory treatment regimens, there has also been increased interest in the use of medicinal mushrooms in bridging the unaddressed pathways of action within the treatment algorithms. In this review, we provide a collection of medicinal mushrooms that are beneficial in promoting respiratory health and potentially reducing COVID-19 symptoms in patients who are newly diagnosed and those who have recovered. While reviewing the use of immunomodulatory pathways, which have shown promising results in tackling side effects and post-COVID syndromes, we also provide insights into how the antioxidant elements present in medicinal mushrooms help to achieve the same results, especially in the prophylactic and therapeutic management of COVID-19 infection. To date, medicinal mushrooms are regarded as a functional food, which, however, need further quality, safety, and efficacy assessments. These requirements are also highlighted in the present review to promote the future development and application of medicinal mushrooms for better respiratory health.
  16. Lim KH, Cheong YL, Sulaiman N, Yah XY, Mahadzir ME, Lim JH, et al.
    Tob Induc Dis, 2022;20:105.
    PMID: 36474605 DOI: 10.18332/tid/155376
    INTRODUCTION: Measuring the level of nicotine addiction among smokers is an integral part of enhancing smoking cessation as nicotine dependence is one of the barriers to smoking cessation. In this study, we compared the level of agreement between FTND and HSI in detecting high nicotine dependence among daily smokers.

    METHODS: We collected data from participants of a public smoking cessation clinic in Selangor. A trained pharmacist conducted face-to-face interviews with 152 daily smokers using a structured validated questionnaire. Respondents were classified as having high nicotine dependence using both the HSI (score ≥4) and the FTND (score ≥6), and concordance between the two measures, kappa statistics and sensitivity, specificity of the HSI were then determined with the FTND classification as the reference standard.

    RESULTS: The HSI had a substantial agreement with the FTND (Cohen's kappa=0.72) in measuring high levels of nicotine addiction, with good sensitivity (83.3%) and specificity (89.4%).

    CONCLUSIONS: The findings suggest that the HSI can be used instead of the FTND in clinical-based investigations to screen for high nicotine dependence among daily smokers in the clinical setting.

  17. Cheah YK, Kee CC, Lim KH, Omar MA
    Pediatr Neonatol, 2021 11;62(6):628-637.
    PMID: 34353744 DOI: 10.1016/j.pedneo.2021.05.025
    BACKGROUND: Mental health disorders are highly correlated with risk behaviors. The objective of the present study is to examine the relationship between risk behaviors and mental health among school-going students with a focus on ethnic minorities.

    METHODS: The National Health and Morbidity Survey (NHMS) 2017 (n = 8230) was used for analyses. It was a nationwide survey conducted in Malaysia. The dependent variables were measured by three risk behaviors (cigarette smoking, alcohol drinking and use of illicit drugs). Probit regressions were utilized to examine the effect of mental health on the probability of smoking, drinking and using illicit drugs. Demographic and lifestyle factors were used as the control variables. Truancy was identified as a mediating variable.

    RESULTS: Anxiety, depression and suicidal ideation affected cigarette smoking, alcohol drinking and use of illicit drugs through mediation of truancy. After controlling for demographic and lifestyle factors, students with anxiety, depression and suicidal ideation were more likely to smoke, drink and use illicit drugs compared with their peers without any mental health disorders. Furthermore, the likelihood of consuming cigarettes, alcohol and illicit drugs was found to be higher among students who played truant than those who did not.

    CONCLUSION: Mental health plays an important role in determining participation in risk behaviors among ethnic minority students in Malaysia. Public health administrators and schools have to be aware that students who suffer from mental health disorders are likely to indulge in risk behaviors.

  18. Tan TL, Tan-Loh J, Chiew SC, Lim KH, Ng WW, Akmal M, et al.
    Med J Malaysia, 2021 Nov;76(6):820-827.
    PMID: 34806667
    INTRODUCTION: Despite the ever-growing number of community onset (CO) Pseudomonas aeruginosa (P. aeruginosa) bacteraemia, there is a dearth of district hospital-based research examining this significant infection, which is associated with high mortality. The objectives of this study were as following: (1) to determine the risk factors of CO P. aeruginosa bacteraemia, (2) to compare the 30-day mortality rate between P. aeruginosa and Escherichia coli bacteraemia and (3) to identify the predictors of 30-day mortality for CO gram negative bacteraemia.

    METHODS: This is a retrospective case control study in Hospital Seri Manjung and Hospital Teluk Intan, Perak, Malaysia. P. aeruginosa bacteraemia cases that occurred between 1st January 2015 to 31st December 2019 were included, whilst E. coli bacteraemia cases that occurred within the same period were recruited successively until 1:2 case control ratio was achieved. Subjects below 12-year-old and those with polymicrobial bacteraemia were excluded. Demographic, clinical and treatment data were collected using pre-tested data collection forms by trained investigators.

    RESULTS: A total of 61 patients with P. aeruginosa bacteraemia and 122 patients with E. coli bacteraemia were included. Recent admission in the earlier three months, regular haemodialysis, immunosuppressive therapy in the past 30 days, chronic wound/pressure sore at presentation and indwelling urinary catheter at presentation were identified as independent predictors of CO pseudomonal bacteraemia. Whilst older age was identified as a negative predictor of CO Pseudomonal bacteraemia (all p<0.05). The 30-day mortality rate was 34.4% in subjects with P. aeruginosa bacteraemia and 27.0% in those with E. coli bacteraemia (p=0.302). Predictors of 30-day mortality for community onset gram negative bacteraemia were as follow: older age, underlying solid tumours, neutropaenia at presentation, in-patient mechanical ventilation, and inpatient nasogastric tube insertion. Unexpectedly, receipt of inappropriate empirical antibiotics which was switched later (delayed and non-delayed switching) was identified as the negative predictors of mortality (all p<0.05).

    CONCLUSION: It is prudent to restrict the usage of empirical anti-pseudomonal antibiotics among individuals at risk as liberal usage of broad-spectrum antibiotics engenders emergence of drug resistant organism, particularly in district setting where community onset pseudomonal bacteraemia remains scarce. Subjects with elevated risk of mortality should receive early escalation of care as per sepsis management guidelines.

  19. Cho ES, Krishnan P, Loh HS, Daly JM, Leong CO, Mai CW, et al.
    Phytochemistry, 2021 Oct 27;193:112988.
    PMID: 34717280 DOI: 10.1016/j.phytochem.2021.112988
    Four undescribed cucurbitacins, designated as petiolaticins A-D, and four known cucurbitacins were isolated from the bark and leaves of Elaeocarpus petiolatus (Jack) Wall. Their chemical structures were elucidated based on detailed analyses of the NMR and MS data. The absolute configuration of petiolaticin A was also determined by X-ray diffraction analysis. Petiolaticin A represents a cucurbitacin derivative incorporating a 3,4-epoxyfuranyl-bearing side chain, while petiolaticin B possesses a furopyranyl unit fused to the tetracyclic cucurbitane core structure. Petiolaticins A, B, and D were evaluated in vitro against a panel of human breast, pancreatic, and colorectal cancer cell lines. Petiolaticin A exhibited the greatest cytotoxicity against the MDA-MB-468, MDA-MB-231, MCF-7, and SW48 cell lines (IC50 7.4, 9.2, 9.3, and 4.6 μM, respectively). Additionally, petiolaticin D, 16α,23α-epoxy-3β,20β-dihydroxy-10αH,23βH-cucurbit-5,24-dien-11-one, and 16α,23α-epoxy-3β,20β-dihydroxy-10αH,23βH-cucurbit-5,24-dien-11-one 3-O-β-D-glucopyranoside were tested for their ability to inhibit cell entry of a pseudotyped virus bearing the hemagglutinin envelope protein of a highly pathogenic avian influenza virus. Petiolaticin D showed the highest inhibition (44.3%), followed by 16α,23α-epoxy-3β,20β-dihydroxy-10αH,23βH-cucurbit-5,24-dien-11-one (21.0%), and 16α,23α-epoxy-3β,20β-dihydroxy-10αH,23βH-cucurbit-5,24-dien-11-one 3-O-β-D-glucopyranoside showed limited inhibition (9.0%). These preliminary biological assays have demonstrated that petiolaticins A and D possess anticancer and antiviral properties, respectively, which warrant for further investigations.
  20. Chan ZY, Krishnan P, Modaresi SM, Hii LW, Mai CW, Lim WM, et al.
    J Nat Prod, 2021 08 27;84(8):2272-2281.
    PMID: 34342431 DOI: 10.1021/acs.jnatprod.1c00374
    Seven new tropane alkaloids, including five monomeric (1-5), one dimeric (6), and one trimeric (7) 3α-nortropane ester, along with two known monomeric nortropane alkaloids (8 and 9), were isolated from the leaves and bark of Pellacalyx saccardianus. Their structures, including the absolute configuration of the enantiomeric pair of (±)-6, were elucidated by comprehensive spectroscopic analyses. Alkaloids 6 and 7 showed cytotoxicity toward human pancreatic cancer cell lines (AsPC-1, BxPC3, PANC-1, and SW1990). Alkaloids 1, 4, and 9 induced a smooth muscle relaxation effect comparable to that of atropine (Emax 106.1 ± 7.5%, 97.0 ± 5.2%, 100.9 ± 1.4%, 111.7 ± 1.7%, respectively) on isolated rat tracheal rings.
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