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.
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.
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.
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.