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  1. Yan P, Eng OC, Yu CJ
    Curr Drug Metab, 2018;19(11):917-929.
    PMID: 29804525 DOI: 10.2174/1389200219666180528090237
    BACKGROUND: Cytochrome P450 2S1 (CYP2S1) is one of the 'orphan' CYPs, which is expressed primarily among extra-hepatic tissues and it is inducible by dioxin. Although the contribution of extra-hepatic CYPs in drug metabolism is considered less significant, they play more important roles in leading to in situ toxicity in organs with higher expression.

    METHOD: A non-systemic search was performed to review articles relevant to CYP2S1 in literature. This review will update the findings related to the expression and regulation of CYP2S1 gene and protein, substrate profiles and metabolism mechanisms, genetic polymorphisms, and their association with diseases.

    RESULTS: The expression of CYP2S1 was mainly in the epithelium of portal of entry organs such as respiratory and gastrointestinal tract. Aryl Hydrocarbon Receptor (AHR) is believed to be partly involved in the induction of CYP2S1. CYP2S1 was found to activate and deactivate pro-drugs which resulted in toxicity and detoxification of carcinogens. The current knowledge of the endogenous functions of CYP2S1 is largely related to cell proliferation and lipid metabolisms. Several polymorphic alleles of CYP2S1 have been reported and documented to date.

    CONCLUSION: Molecular-based investigations should be performed to better understand the regulation mechanism of CYP2S1 in various cells and tissues. It is pivotal to establish optimum expression and incubation systems in vitro to elucidate the substrate specificity of CYP2S1 and characterise the genetic consequences of variant CYP2S1 in vitro.

  2. Chong ZX, Ho WY, Yan P, Alshagga MA
    Asian Pac J Cancer Prev, 2020 Apr 01;21(4):881-895.
    PMID: 32334447 DOI: 10.31557/APJCP.2020.21.4.881
    BACKGROUND: Conducting systematic review to evaluate plant use as a risk factor to cancer could be challenging. A systematic and well-balanced method should be applied to accommodate in vivo and in vitro studies to make a final decision. In this article, khat, a recreational plant used in some Arabic and African regions, was employed as an example to systematically determine its relationships to the premalignant and cancerous conditions.

    METHODS: Systematic database search was performed to recruit original human, animal or in vitro studies on khat and cancer. Sixteen studies fulfilled the inclusion criteria and subjected to assessment using Risk of Bias (RoB). Office of Health and Translation (OHAT) approach was used to rate the confidence level in the body of evidence. The evidence was integrated to establish the relationships between khat, premalignant conditions and cancer.

    RESULTS: Seven out of eight studies showed that khat causes premalignant oral lesions with moderate evidence level. Four studies showed that khat causes cancer with low evidence level and another three studies showed that khat has anti-cancer effect with moderate to high evidence level. Only one study suggested that khat is unrelated to cancer.

    CONCLUSION: RoB and OHAT approach are reliable systematic tools to evaluate plant risk to cancer and provide objective and uniform summary regardless of the study type. In conclusion, our pooled analysis did not find a direct relationship between khat and cancer but anti-cancer effect would require to be proofed on human studies.

  3. Kim HS, Wu Y, Lin SJ, Deerochanawong C, Zambahari R, Zhao L, et al.
    Curr Med Res Opin, 2008 Jul;24(7):1951-63.
    PMID: 18547466 DOI: 10.1185/03007990802138731
    BACKGROUND: Data on achieving National Cholesterol Education Program Adult Treatment Panel III (ATP III) goals in Asia are limited.

    OBJECTIVE: To examine treatment patterns, goal attainment, and factors influencing treatment among patients in 6 Asian countries who were taking statins.

    METHODS: A retrospective cohort study was conducted in China, Korea, Malaysia, Singapore, Taiwan, and Thailand, where 437 physicians (41% cardiologists) recruited adults with hypercholesterolemia newly initiated on statin monotherapy.

    RESULTS: Of 2622 patients meeting inclusion and exclusion criteria, approximately 66% had coronary heart disease (CHD)/diabetes mellitus, 24% had no CHD but > or =2 risk factors, and 10% had no CHD and <2 risk factors. Most patients ( approximately 90%) received statins at medium or lower equipotency doses. Across all cardiovascular risk categories, 48% of patients attained ATP III targets for low-density lipoprotein cholesterol (LDL-C), including 38% of those with CHD/diabetes (goal: <100 mg/dL), 62% of those without CHD but with > or =2 risk factors (goal: <130 mg/dL), and 81% of those without CHD and <2 risk factors (goal: <160 mg/dL). Most patients who achieved goals did so within the first 3 months. Increasing age (odds ratio (OR)=1.015 per 1-year increment; 95% confidence interval (CI)=1.005-1.206; p=0.0038) and initial statin potency (OR=2.253; 95% CI=1.364-3.722; p=0.0015) were directly associated with goal attainment, whereas increased cardiovascular risk (OR=0.085; 95% CI=0.053-0.134; p<0.0001 for CHD/diabetes mellitus at baseline compared with <2 risk factors,) and baseline LDL-C (OR=0.990; 95% CI=0.987-0.993); p<0.0001 per 1-mg/dL increment) were inversely associated with LDL-C goal achievement. Limitations of this study include potential differences in treatment settings and cardiovascular risk factors between different countries and centers. In addition, the effects on cholesterol goal achievement of concomitant changes in lifestyle were not assessed.

    CONCLUSION: LDL-C goal attainment is low in Asians, particularly those with CHD/diabetes. More effective patient monitoring, treatments, including combining regimens and dose titration, and adherence to these treatments along with therapeutic lifestyle counseling may facilitate goal attainment.

  4. She W, Qi T, Cui M, Yan P, Ng SW, Li W, et al.
    ACS Appl Mater Interfaces, 2018 May 02;10(17):14698-14707.
    PMID: 29638107 DOI: 10.1021/acsami.8b01187
    A family of two-dimensional salen-type lanthanide complexes was synthesized through a facile solution diffusion method. The two-dimensional lanthanide complexes were characterized by single-crystal X-ray diffraction (SCXRD) and X-ray photoelectron spectroscopy (XPS) analytical techniques. The SCXRD and XPS analyses reveal that the obtained two-dimensional structures are rich in uncoordinated imine (-CH═N-) groups located on the skeleton of the salen-type organic ligand, which retain strong coordination ability with metal ions. On the basis of this unique feature, a highly dispersed CeO2-supported Ni catalyst (Ni/CeO2-CAS) with highly strong metal-support interaction was first synthesized via a coordination-assisted synthesis (CAS) method, which exhibits a much better catalytic activity in the hydrogenation of nitrobenzene than the traditional Ni/CeO2-IWI catalyst prepared by incipient wetness impregnation (IWI). The origin of the improved catalytic activity of Ni/CeO2-CAS as well as the role of Ni@Ce-H2salen was revealed by using diverse characterizations. On the basis of the comparative characterization results, the superior catalytic performance of Ni/CeO2-CAS to Ni/CeO2-IWI could have resulted from the smaller and highly dispersed Ni nanoparticulates, the intensified Ni-CeO2 interaction, the enhanced NiO reducibility, and the higher concentration of oxygen vacancies, favoring the H2 dissociation and adsorption of the nitrobenzene reactant. The Ni/CeO2-CAS catalyst also exhibits high catalytic performance for reduction of diverse nitroarenes to their corresponding functionalized arylamines. We anticipated that this coordination-assisted strategy may provide a new way for preparing other highly oxide-supported catalysts with potential applications in various catalytic reactions.
  5. Tan HS, Yan P, Agustie HA, Loh HS, Rayamajhi N, Fang CM
    Lett Appl Microbiol, 2023 Jan 23;76(1).
    PMID: 36688778 DOI: 10.1093/lambio/ovac044
    Extended-spectrum beta-lactamases (ESBLs) and AmpC beta-lactamases (AmpCs)-producing Enterobacteriaceae have been increasingly reported and imposing significant threat to public. Livestock production industry might be the important source for clinically important ESBL-producing Enterobacteriaceae. This study aims to investigate the resistance profile, phenotypic ESBL production, beta-lactamase genes, virulence factors, and plasmid replicon types among 59 Enterobacteriaceae strains isolated from poultry faecal samples in Malaysia's commercial poultry farm. There were 38.7% and 32.3% of Escherichia coli resistant to cefotaxime and cefoxitin, respectively, while Klebsiellaspp. demonstrated resistance rate of 52.6% to both mentioned antimicrobials. Majority of the E. coli isolates carried blaTEM and blaCMY-2 group. blaSHV was the most prevalent gene detected in Klebsiellaspp., followed by blaDHA and blaTEM. Resistance to extended spectrum cephalosporin in our isolates was primarily mediated by plasmid mediated AmpC beta-lactamase such as CMY-2 group and DHA enzyme. The CTX-M genes were found in two ESBL-producing E. coli. IncF, IncI1, and IncN plasmids were most frequently detected in E. coli and Klebsiellaspp. The virulence factor, including EAST1 and pAA were identified at low frequency. This study highlights the poultry as a reservoir of resistance and virulence determinants and prevalence of plasmids in Enterobacteriaceae might drive their dissemination.
  6. An C, Xue H, Dong Z, Xiao D, Xue J, Yan J, et al.
    ACS Omega, 2023 Aug 15;8(32):29346-29358.
    PMID: 37599934 DOI: 10.1021/acsomega.3c02431
    Hybrid sedimentary rocks (HSR) represent a significant reservoir type in fine-grained sediments. However, the classification and understanding of HSR reservoirs, including their storage mechanisms and identification of optimal "sweet spots," have been limited due to the lack of clarity regarding the multiple sources of components and their mixing processes. This study focuses on the Lucaogou formation of Jimusaer Sag and aims to highlight the reservoir classification principles, controlling factors, and evolutionary patterns associated with the components of HSR, beginning with examining the microscopic pore structure. The analysis of the microscopic pore structure characteristics reveals the presence of five distinct reservoir types within the HSR. The quality of these reservoirs is governed by various factors, including the composition and support mode of particles, diagenesis, provenance, and sedimentary microfacies. In regions near a provenance with strong hydrodynamic conditions, the HSR predominantly exhibits type I and type II reservoirs, characterized by numerous coarse-grained components and a granular-support mode. As the distance from the provenance increases, transitioning into medium hydrodynamic conditions, the HSR shifts to an interbedded-support mode, primarily developing type III reservoirs. In areas far from the provenance with weak hydrodynamic conditions, HSR reservoir types primarily consist of type IV and type V. Additionally, diagenetic effects such as compaction and calcite cementation further deteriorate intergranular and dissolution pores, consequently diminishing reservoir quality. Notably, during the mixing deposition processes of sand and dolomite, the developmental mode of HSR shifts from type I to type II and type III. Likewise, in the mixing deposition of mud and sand, the HSR transitions from type II to type III and type IV. Similarly, the mixing deposition of dolomite and mud leads to a change in the developmental mode of HSR from type III to type IV and type V. Moreover, this study effectively predicts the occurrence of "sweet spots" using reservoir classification, which reveals their continuous distribution. These findings provide a geological foundation for evaluating "sweet spots" and testing the oil production in HSR reservoirs.
  7. Yan P, Tze UY, Jagadish PAR, Hon LK, Chowdhury LNS, Tao S, et al.
    Drug Metab Bioanal Lett, 2022;15(3):178-191.
    PMID: 36508274 DOI: 10.2174/1872312815666220707114744
    BACKGROUND: Agarwood tea derived from Aquilaria malaccensis Lamk is becoming an increasingly popular herbal drink that is said to have multiple health benefits. Co-administration of this tea and clinical used drugs is possible, but it increases the risk of drug-herb interactions.

    OBJECTIVE: This in vitro study investigated the inhibitory effects of agarwood tea aqueous extract on the eight major human drug-metabolising cytochrome P450 (CYP) enzyme activities.

    METHODS: High-throughput fluorescence-based Vivid® CYP450 screening kits were employed to obtain the enzyme activities before and after incubation with agarwood tea aqueous extract.

    RESULTS: Agarwood aqueous extract potently inhibited CYP2C9, CYP2D6, and CYP3A4 activities with Ki values of 5.1, 34.5, and 20.3μg/ml, respectively. The most likely inhibition mode responsible for these inhibitions was non-competitive inhibition. On the other hand, at 1000μg/ml, agarwood tea aqueous extract negligibly inhibited CYP1A2, CYP2B6, CYP2C19, CYP2E1, and CYP3A5 activities.

    CONCLUSION: These findings can be used to design additional in vitro investigations using clinical relevant drug substrates for CYP2C9, CYP2D6, and CYP3A4. Subsequently, future studies can be conducted to determine potential interactions between agarwood tea aqueous extract and CYP using in vivo models.

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