METHODS: This study was designed to investigate the effect of SynacinnTM and its individual biomarkers on drug metabolizing enzymes (CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A4 (Midazolam), CYP3A4 (Testosteron)), to assess its herb-drug interaction potential through cytochrome P450 inhibition assay. This study was conducted using liquid chromatography- tandem mass spectroscopy (LC-MS/MS) using probe substrates using human liver microsomes against CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A4 (Midazolam) and CYP3A4 (Testosteron).
RESULTS: Result showed that SynacinnTM at maximum concentration (5000 µg/ml) 100% inhibit CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A4 (Midazolam) and CYP3A4 (Testosteron). IC50 values determined were 0.23, 0.60, 0.47, 0.78, 1.23, 0.99, 1.01, and 0.91 mg/ml for CYP 1A2, 2B6, 2C8, 2C9, 2C19, 2D6, 3A4 (midazolam) and 3A4 (testosterone), respectively. Meanwhile, all individual biomarkers showed no, less or moderate inhibitory effect towards all the tested CYP450 except for curcumin that showed inhibition of CYP2C8 (91%), CYP2C9 (81%) and CYP2C19 (72%) at 10µM.
CONCLUSION: Curcumin was found to be an active constituent that might contribute to the inhibition of SynacinnTM against CYP2C8, CYP2C9 and CYP2C19. It can be suggested that SynacinnTM can be consumed separately from a drug known to be metabolized by all tested CYP450 enzymes.
OBJECTIVES: Evaluating group of selective oxidative stress markers as a tool in the management of asthma disease.
METHODS: In comparison with matched healthy controls, levels of the oxidant and antioxidant markers: lipid peroxidation malondialdehyde (MDA), Total glutathione (tGSH), Uric acid (UA), Glutathione peroxidase (GPx), Catalase (CAT) superoxide dismutase (SOD), and Total antioxidant capacity (TAC) were assessed in serum and saliva of different asthma groups.
RESULTS: All oxidative markers in serum and saliva of asthma patients showed significant alterations from normal healthy controls (P 0.05).
CONCLUSION: Determination of the oxidative markers GPx, CAT, UA in serum or saliva can distinguish asthma from healthy states. The serum levels of UA and TAC are highly effective in monitoring asthma severity, while the salivary GPx, CAT, UA, MDA are beneficial in the management of childhood asthma. Discrimination of the age factor between asthma groups can be achieved by testing GPx, SOD, TAC in serum.
Aim: The objective of this research was to investigate the acute effects of tributyltin chloride (TBTCl) on gonads in the adult stage of Artemia salina by use normal histology and immunohistochemistry (IHC) (Caspase 3 and HSP70) to see specific apoptosis markers.
Methods: After exposure of A. salina to different concentrations of TBTCl (25, 50, 100, 200, and 300 ng.l-1), 50 adult A. salina (25 male and 25 female) were selected randomly from each concentration to histologically study the gonads. The gonad tissue was sectioned (5 μm) and some slides were stained with hematoxylin and eosin and others were stained with IHC avidin-biotin complex, and were examined under a light microscope.
Results: The results showed significant differences (p < 0.05) in histological lesions between different concentrations of TBTCl. The histological lesions in the testis and ovary section were undifferentiated cells, degenerating yolk globules, and follicle cells enveloping the oocyte which was then compared with control tissue, and these effects were found to be increased in females more than in males with the highest concentration of TBTCl. Immunohistochemistry (IHC) showed that positive immunostaining was observed in the testis and ovary as brownish deposits to Caspase 3 and HSP70 antibody after exposure to TBTCl, while the testis and ovary section in control tissue had no immunoreactivity to Caspase 3 and HSP70 antibody; these effects were profoundly increased with the highest concentration of TBTCl in females more than in males. Finally, the histological lesions and IHC (Caspase 3 and HSP70) revealed that the apoptosis and immune system stress of A. salina gonad tissue damage in females were more sensitive to TBTCl toxicity as compared to white males.
Conclusion: In general, the present study aimed to observe the effects TBTCl on A. salina gonads by using histological sections and IHC (Caspase 3 and HSP70), which were evaluated for the first time and have been proven to possess an important function in apoptosis marker and immune system stress in Artemia. Finally, the specific mechanisms through which TBTCl affects A. salina Caspase 3 and HSP70 expression need further investigation.
AIM: Our objective was to investigate the potential of AOC3 and LRRC17 as biomarkers for fibroblast activation thus predicting their roles in CRC progression.
METHODS: Immunofluorescence (IF) staining of AOC3 and LRRC17 was performed on myofibroblast line (CCD-112CoN), primary fibroblasts from colorectal tumor (CAFs), and adjacent normal tissue (normal fibroblasts-NFs). SW620 (epithelial CRC cell line) was used as a control. Conventional CAF biomarker (alpha-smooth muscle actin - α-SMA) was included in the IF analysis. Fluorescence intensity was compared between groups using ImageJ software. Proliferation and contractility of treated cells were assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) and collagen gel contraction assays, respectively. Fibroblast contraction under TGF-β1 treatment was compared to those treated with complete medium (addition of 10% serum) and serum free (SF) medium.
RESULTS: Positive AOC3, LRRC17, and α-SMA expression were observed in colonic fibroblasts, more prominent in CAFs, whereas negative staining was found in SW620. Significant downregulation of AOC3, and upregulations in LRRC17 and α-SMA expression was found in TGF-β1-treated fibroblasts compared to SF medium treatment (p-value<0.05). All fibroblasts exhibited higher proliferation in complete medium and under treatment with conditioned medium from SW620 than SF medium. Significant contraction of NFs was recorded in complete medium and TGF-β1 (p-value<0.01).
CONCLUSION: Our results demonstrate AOC3 and LRRC17 as the potential markers of CAF activation which promote CRC progression.
Methods: : We utilized data among 1020 infants from a mother-offspring cohort, who were Singapore citizens or permanent residents of Chinese, Malay or Indian ethnicity with homogeneous parental ethnic backgrounds, and did not receive chemotherapy, psychotropic drugs or have diabetes mellitus. Ethnicity was self-reported at recruitment and later confirmed using genotype analysis. Subject-specific BMI curves were fitted to infant BMI data using natural cubic splines with random coefficients to account for repeated measures in each child. We estimated characteristics of the child's BMI peak [age and magnitude at peak, average pre-peak velocity (aPPV)]. Systolic (SBP) and diastolic blood pressure (DBP), BMI, sum of skinfolds (SSF) and fat-mass index (FMI) were measured during a follow-up visit at age 48 months. Weighted multivariable linear regression was used to assess the predictors (maternal BMI, gestational weight gain, ethnicity, infant sex, gestational age, birthweight-for-gestational age and breastfeeding duration) of infant BMI peak and its associations with outcomes at 48 months. Comparisons between ethnicities were tested using Bonferroni post-hoc correction.
Results: : Of 1020 infants, 80.5% were followed up at the 48-month visit. Mean (SD) BMI, SSF and FMI at 48 months were 15.6 (1.8) kg/m 2 , 16.5 (5.3) mm and 3.8 (1.3) kg/m 2 , respectively. Mean (SD) age at peak BMI was 6.0 (1.6) months, with a magnitude of 17.2 (1.4) kg/m 2 and pre-peak velocity of 0.7 (0.3) kg/m 2 /month. Compared with Chinese infants, the peak occurred later in Malay {B [95% confidence interval (CI): 0.64 mo (0.36, 0.92)]} and Indian infants [1.11 mo (0.76, 1.46)] and was lower in magnitude in Indian infants [-0.45 kg/m 2 (-0.69, -0.20)]. Adjusting for maternal education, BMI, gestational weight gain, ethnicity, infant sex, gestational age, birthweight-for-gestational-age and breastfeeding duration, higher peak and aPPV were associated with greater BMI, SSF and FMI at 48 months. Age at peak was positively associated with BMI at 48 months [0.15 units (0.09, 0.22)], whereas peak magnitude was associated with SBP [0.17 units (0.05, 0.30)] and DBP at 48 months [0.10 units (0.01, 0.22)]. Older age and higher magnitude at peak were associated with increased risk of overweight at 48 months [Relative Risk (95% CI): 1.35 (1.12-1.62) for age; 1.89 (1.60-2.24) for magnitude]. The associations of BMI peak with BMI and SSF at 48 months were stronger in Malay and Indian children than in Chinese children.
Conclusions: : Ethnic-specific differences in BMI peak characteristics, and associations of BMI peak with early childhood cardio-metabolic markers, suggest an important impact of early BMI development on later metabolic outcomes in Asian populations.