Plant-Based Diet and Glycemic Control in Type 2 Diabetes: Evidence from a Thai Health-Promoting Hospital.

The prevalence of type 2 diabetes (T2DM) is associated with diet. While consumption of plant-based foods may reduce blood sugar levels, the impact of consuming plant-based foods on fasting blood sugar levels has not been well defined. This cross-sectional study was conducted at the Health-Promoting Hospital in Pak Phun Municipality, Thailand. It included 61 patients with T2DM and 74 controls matched for age and gender. Dietary intake levels among T2DM and controls were assessed by a validated food-frequency questionnaire from which plant-based-food scores were calculated. This study found significant differences between specific plant foods and fasting blood sugar levels in patients with T2DM. Adherence to a plant-based diet appeared to influence fasting blood sugar levels. Patients who consumed higher amounts of certain vegetables and fruits showed lower fasting blood sugar levels. Diabetic patients consumed more legumes than controls, but the consumption of cereals and nuts/seeds in the two groups were similar. Consumption of nuts and seeds was also associated with a 76.3% reduction in the risk of a T2DM diagnosis. These findings suggest the potential efficacy of glycemic control in T2DM patients. More work is required to explore strategies for preventing and treating metabolic disorders through dietary modification.

Estimation of the Cadmium Nephrotoxicity Threshold from Loss of Glomerular Filtration Rate and Albuminuria.

Cadmium (Cd) is a pervasive, toxic environmental pollutant that preferentially accumulates in the tubular epithelium of the kidney. Current evidence suggests that the cumulative burden of Cd here leads to the progressive loss of the glomerular filtration rate (GFR). In this study, we have quantified changes in estimated GFR (eGFR) and albumin excretion (Ealb) according to the levels of blood Cd ([Cd]b) and excretion of Cd (ECd) after adjustment for confounders. ECd and Ealb were normalized to creatinine clearance (Ccr) as ECd/Ccr and Ealb/Ccr. Among 482 residents of Cd-polluted and non-polluted regions of Thailand, 8.1% had low eGFR and 16.9% had albuminuria (Ealb/Ccr) × 100 ≥ 20 mg/L filtrate. In the low Cd burden group, (ECd/Ccr) × 100 < 1.44 µg/L filtrate, eGFR did not correlate with ECd/Ccr (ß = 0.007) while an inverse association with ECd/Ccr was found in the medium (ß = -0.230) and high burden groups (ß = -0.349). Prevalence odds ratios (POR) for low eGFR were increased in the medium (POR 8.26) and high Cd burden groups (POR 3.64). Also, eGFR explained a significant proportion of Ealb/Ccr variation among those with middle (η2 0.093) and high [Cd]b tertiles (η2 0.132) but did not with low tertiles (η2 0.001). With an adjustment of eGFR, age and BMI, the POR values for albuminuria were increased in the middle (POR 2.36) and high [Cd]b tertiles (POR 2.74) and those with diabetes (POR 6.02) and hypertension (2.05). These data indicate that (ECd/Ccr) × 100 of 1.44 µg/L filtrate (0.01-0.02 µg/g creatinine) may serve as a Cd threshold level based on which protective exposure guidelines should be formulated.

Effect of Green and Red Thai Kratom (Mitragyna speciosa) on pancreatic digestive enzymes (alpha-glucosidase and lipase) and acetyl-carboxylase 1 activity: A possible therapeutic target for obesity prevention.

Regular use of Thai kratom has been linked to reduced blood triglyceride levels and body mass index (BMI) in healthy individuals. We analyzed Green Thai Kratom (GTK) and Red Thai Kratom (RTK) to investigate their effects on pancreatic digestive enzymes. The ethanol extracts of GTK and RTK inhibited lipase activity more strongly than alpha-glucosidase activity, suggesting the presence of lipase inhibitors. Mitragynine, the major compound in GTK, showed potent lipase inhibition and moderate alpha-glucosidase inhibition. Quercetin, found in both extracts, strongly inhibited alpha-glucosidase but had limited effects on lipase. These findings suggest that mitragynine and quercetin may hinder triglyceride and starch digestion. Combination inhibition studies revealed synergistic effects between mitragynine and quercetin on alpha-glucosidase activity. Additionally, both GTK and RTK extracts reduced fat accumulation in 3T3-L1 adipocyte cells, with quercetin specifically inhibiting Acetyl-CoA carboxylase 1 (ACC1), a key enzyme in fatty acid biosynthesis. Thus, GTK and RTK extracts, particularly mitragynine and quercetin, exhibit potential anti-obesity effects. We report the novel finding that Thai kratom inhibits de novo fatty acid synthesis by targeting ACC1, resulting in decreased fat accumulation in adipocytes. Regular use of Thai kratom in specific populations may improve blood triglyceride levels and reduce BMI by inhibiting lipase, alpha-glucosidase, and ACC1 activity. Further clinical trials are needed to determine optimal dosage, duration, toxicity levels, and potential side effects of Kratom use.

Negative impact of smoking on lung function: comparing FEV1/FVC values in smokers and non-smokers.

Background: Cigarette smoking has been reported as the significant adverse effects on lung function, which can be evaluated by measuring forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and the ratio of FEV1 to FVC (FEV1/FVC) values. Objective: This study investigated the prevalence of tobacco use and nicotine dependence among college students and their stress levels to inform targeted interventions for smoking prevention and cessation. Material and methods: A total of 429 participants were interviewed face-to-face, of which 71.6% were female and 28.4% were male. Pulmonary function tests were exclusively administered to the 9.8% of participants who reported using tobacco. Results: Our findings revealed a low prevalence of nicotine dependence among college students, with only 6.8% exhibiting moderate or high levels of dependence. Students who reported tobacco use were found to have moderate stress levels,suggesting a potential association between smoking and stress. Chi-square tests revealed that gender, school affiliation,and nicotine dependence were significantly associated with smoking behavior. Long-term smoking (>5 years) was found to be associated with negative health outcomes, such as higher BMI, and increased smoking per day. The analysis of lung function parameters showed that smoking frequency and duration were negatively associated with lung function, while nicotine dependence increased with smoking frequency and duration. Conclusion: Our study suggests that targeted prevention and cessation programs should address these factors to reduce smoking rates among college students.

Gender Differences in the Severity of Cadmium Nephropathy.

The excretion of ß2-microglobulin (ß2M) above 300 µg/g creatinine, termed tubulopathy, was regarded as the critical effect of chronic exposure to the metal pollutant cadmium (Cd). However, current evidence suggests that Cd may induce nephron atrophy, resulting in a reduction in the estimated glomerular filtration rate (eGFR) below 60 mL/min/1.73 m2. Herein, these pathologies were investigated in relation to Cd exposure, smoking, diabetes, and hypertension. The data were collected from 448 residents of Cd-polluted and non-polluted regions of Thailand. The body burden of Cd, indicated by the mean Cd excretion (ECd), normalized to creatinine clearance (Ccr) as (ECd/Ccr) × 100 in women and men did not differ (3.21 vs. 3.12 µg/L filtrate). After adjustment of the confounding factors, the prevalence odds ratio (POR) for tubulopathy and a reduced eGFR were increased by 1.9-fold and 3.2-fold for every 10-fold rise in the Cd body burden. In women only, a dose-effect relationship was seen between ß2M excretion (Eß2M/Ccr) and ECd/Ccr (F = 3.431, η2 0.021). In men, Eß2M/Ccr was associated with diabetes (ß = 0.279). In both genders, the eGFR was inversely associated with Eß2M/Ccr. The respective covariate-adjusted mean eGFR values were 16.5 and 12.3 mL/min/1.73 m2 lower in women and men who had severe tubulopathy ((Eß2M/Ccr) × 100 ≥ 1000 µg/L filtrate). These findings indicate that women were particularly susceptible to the nephrotoxicity of Cd, and that the increment of Eß2M/Ccr could be attributable mostly to Cd-induced impairment in the tubular reabsorption of the protein together with Cd-induced nephron loss, which is evident from an inverse relationship between Eß2M/Ccr and the eGFR.

Enhancing the Effective Chemotherapy: The Combined Inhibition of Rhinacanthin-C, 5-Fluorouracil, and Etoposide on Oral Cancer Cells.

OBJECTIVE: To investigate the effects of rhinacanthin-C (Rh-C), 5-FU, and etoposide on growth inhibition, as well as the effects of a combination of these inhibitors on the oral cell lines SCC9 and HSC4. METHODS: Cancer cell growth inhibition and inhibition combination were determined using the SRB assay. Cell viability and early apoptosis were determined using flow cytometry on cells stained with Annexin 5 and PI. Western blotting was performed to study the molecular mechanism of these inhibitors on oral cancer cells. RESULTS: The results showed that etoposide, 5-FU, and Rh-C exhibited more potent anti-proliferative effects on HSC4 cells compared to SCC9 cells in a time- and concentration-dependent manner. The combination of Rh-C and 5-FU was more effective in inhibiting cell growth than the drugs used alone. The combination of 5-FU and Rh-C resulted in a decrease in live HSC4 cells, with the highest percentage of cell death observed at a ratio of 40:6 µM. Furthermore, the combination of 5-FU and Rh-C reduced P-Akt levels leading to a decrease in cell survival. CONCLUSIONS: HSC4 cells were found to be more sensitive to the inhibitory effect of these drugs compared to SCC9 cells. These findings suggest that the use of Rh-C as a complementary therapy with 5-FU may have the potential for the treatment of oral cancer. the underlying mechanisms responsible for this difference in sensitivity between the two cell lines need to be further investigated.

Evidence Linking Cadmium Exposure and ß2-Microglobulin to Increased Risk of Hypertension in Diabetes Type 2.

The most common causes of chronic kidney disease, diabetes, and hypertension are significant public health issues worldwide. Exposure to the heavy metal pollutant, cadmium (Cd), which is particularly damaging to the kidney, has been associated with both risk factors. Increased levels of urinary ß2-microglobulin (ß2M) have been used to signify Cd-induced kidney damage and circulating levels have been linked to blood pressure control. In this study we investigated the pressor effects of Cd and ß2M in 88 diabetics and 88 non-diabetic controls, matched by age, gender and locality. The overall mean serum ß2M was 5.98 mg/L, while mean blood Cd and Cd excretion normalized to creatinine clearance (Ccr) as ECd/Ccr were 0.59 µg/L and 0.0084 µg/L of filtrate (0.95 µg/g creatinine), respectively. The prevalence odds ratio for hypertension rose by 79% per every ten-fold increase in blood Cd concentration. In all subjects, systolic blood pressure (SBP) showed positive associations with age (ß = 0.247), serum ß2M (ß = 0.230), and ECd/Ccr (ß = 0.167). In subgroup analysis, SBP showed a strong positive association with ECd/Ccr (ß = 0.303) only in the diabetic group. The covariate-adjusted mean SBP in the diabetics of the highest ECd/Ccr tertile was 13.8 mmHg higher, compared to the lowest tertile (p = 0.027). An increase in SBP associated with Cd exposure was insignificant in non-diabetics. Thus, for the first time, we have demonstrated an independent effect of Cd and ß2M on blood pressure, thereby implicating both Cd exposure and ß2M in the development of hypertension, especially in diabetics.

Induction of S arrest and apoptosis in human oral cancer cells by Rhinacanthin-C extracted from Rhinacanthus nasutus via modulating Akt and p38 signaling pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: The search for effective herbal medicines for complementary treatments is on the rise due to the high incidence of recurrence and mortality rate in human oral cancer. Rhinacanthus nasutus KURZ., an annual herb found mostly in Southeast Asia including Thailand, has been wildly used as a traditional folk medicine for the treatment of several diseases including cancer. However, the anti-cancer effect of Rhinacanthin-C (Rh-C) as a major naphthoquinone compound found in R. nasutus and the underlying mechanism of its action on human oral cancer cells remain unknown. AIM OF THE STUDY: To investigate the anti-cancer mechanism of Rh-C extracted from R. nasutus in human oral cancer cells. MATERIALS AND METHODS: The anti-proliferative effect of Rh-C on human oral squamous cell carcinoma (HSC4) was determined and compared to normal oral cells (human gingival fibroblasts, HGF, and normal oral keratinocytes, NOK) using the SRB colorimetric method. The molecular mechanism of Rh-C was explored using flow cytometry, colorimetric assay, in vitro human topoisomerase II assay, and Western blotting. RESULTS: Rh-C displayed a time- and concentration-dependent growth inhibition on HSC4 and was much less effective on both tested normal oral cells. Rh-C inhibited Akt phosphorylation whereas over-activated p38 MAPK phosphorylation in HSC4 but not in HGF. Rh-C also inhibited topoisomerase II activity. As a result, the cell cycle was arrested in S-phase as the expression of CDK1/2 and Cyclin A2 was decreased. Eventually, the induction of HSC4 cell apoptosis was mediated by increased caspase 3 activity. CONCLUSIONS: Rh-C isolated from R. nasutus possesses anti-cancer properties on human oral cancer cells by causing the S arrest and the apoptotic induction via modulating Akt/p38 signaling pathways. The results provide molecular bases for further developing Rh-C as a potential drug candidate or a complementary treatment for oral cancer.

Chronic Kidney Disease Induced by Cadmium and Diabetes: A Quantitative Case-Control Study.

Kidney disease associated with chronic cadmium (Cd) exposure is primarily due to proximal tubule cell damage. This results in a sustained decline in glomerular filtration rate (GFR) and tubular proteinuria. Similarly, diabetic kidney disease (DKD) is marked by albuminuria and a declining GFR and both may eventually lead to kidney failure. The progression to kidney disease in diabetics exposed to Cd has rarely been reported. Herein, we assessed Cd exposure and the severity of tubular proteinuria and albuminuria in 88 diabetics and 88 controls, matched by age, gender and locality. The overall mean blood and Cd excretion normalized to creatinine clearance (Ccr) as ECd/Ccr were 0.59 µg/L and 0.0084 µg/L filtrate (0.96 µg/g creatinine), respectively. Tubular dysfunction, assessed by ß2-microglobulin excretion rate normalized to Ccr(Eß2M/Ccr) was associated with both diabetes and Cd exposure. Doubling of Cd body burden, hypertension and a reduced estimated GFR (eGFR) increased the risks for a severe tubular dysfunction by 1.3-fold, 2.6-fold, and 84-fold, respectively. Albuminuria did not show a significant association with ECd/Ccr, but hypertension and eGFR did. Hypertension and a reduced eGFR were associated with a 3-fold and 4-fold increases in risk of albuminuria. These findings suggest that even low levels of Cd exposure exacerbate progression of kidney disease in diabetics.

Cadmium-Induced Tubular Dysfunction in Type 2 Diabetes: A Population-Based Cross-Sectional Study.

The global prevalence of diabetes, and its major complication, diabetic nephropathy, have reached epidemic proportions. The toxic metal cadmium (Cd) also induces nephropathy, indicated by a sustained reduction in the estimated glomerular filtration rate (eGFR) and the excretion of ß2-microglobulin (ß2M) above 300 µg/day, which reflects kidney tubular dysfunction. However, little is known about the nephrotoxicity of Cd in the diabetic population. Here, we compared Cd exposure, eGFR, and tubular dysfunction in both diabetics (n = 81) and non-diabetics (n = 593) who were residents in low- and high-Cd exposure areas of Thailand. We normalized the Cd and ß2M excretion rates (ECd and Eß2M) to creatinine clearance (Ccr) as ECd/Ccr and Eß2M/Ccr. Tubular dysfunction and a reduced eGFR were, respectively, 8.7-fold (p < 0.001) and 3-fold (p = 0.012) more prevalent in the diabetic than the non-diabetic groups. The doubling of ECd/Ccr increased the prevalence odds ratios for a reduced eGFR and tubular dysfunction by 50% (p < 0.001) and 15% (p = 0.002), respectively. In a regression model analysis of diabetics from the low-exposure locality, Eß2M/Ccr was associated with ECd/Ccr (ß = 0.375, p = 0.001) and obesity (ß = 0.273, p = 0.015). In the non-diabetic group, Eß2M/Ccr was associated with age (ß = 0.458, p < 0.001) and ECd/Ccr (ß = 0.269, p < 0.001). However, after adjustment for age, and body mass index (BMI), Eß2M/Ccr was higher in the diabetics than non-diabetics of similar ECd/Ccr ranges. Thus, tubular dysfunction was more severe in diabetics than non-diabetics of similar age, BMI, and Cd body burden.

Sugar-sweetened beverages consumption during Covid-19 pandemic among office workers in semi-urban area in southern Thailand: a cross-sectional study.

Background: During COVID-19 pandemic, office worker has spent more than 6-8 hours per day sitting for online working following social distancing policy. Considering the popularity of online ordering and home delivery services, sugar-sweetened beverages (SSB) consumption have increased. However, the link between the types SSB consumption and their BMI was less well documented. Objective: To determine the association of the habitual intake (type, frequency, and volume) of sugar-sweetened beverages (SSB) with body mass index (BMI). Material and methods: A cross-sectional study, 337 office workers were selected according to probability proportionto-size and systematic random sampling. Data were collected using face-to-face interviews on the type, frequency, and volume of sugar-sweetened beverage intake. Samples of sugar-containing beverages were analyzed using high-throughput liquid chromatography/mass spectrometry (LC-MS/MS). The chi-square test was used to determine the relationship of SSB consumption with BMI. Unadjusted binary logistic regression analysis was used to assess the associations between BMI and metabolic diseases. Results: Most respondents (56.1%) were overweight (BMI >23 kg/m2). The most consumed SSB was milk tea (e.g., Thai tea and green tea), which was significantly related with BMI (p=0.03). LC-MS/MS analysis showed that sucrose and lactose were the major sugars in milk tea (34.7 g/100mL, on average). 70.6% of the respondents consumed >24 g/day of sugar, which is more than the World Health Organization's recommendation. Conclusions: Health control policies and health education, for example warning labels for the reduction of SSB consumption, may urgently be required to promote health in workplaces and prevent SSB-related metabolic diseases.

Inhibition of α-Glucosidase and Pancreatic Lipase Properties of Mitragyna speciosa (Korth.) Havil. (Kratom) Leaves.

Kratom (Mitragyna speciosa (Korth.) Havil.) has been used to reduce blood sugar and lipid profiles in traditional medicine, and mitragynine is a major constituent in kratom leaves. Previous data on the blood sugar and lipid-altering effects of kratom are limited. In this study, phytochemical analyses of mitragynine, 7-hydroxymitragynine, quercetin, and rutin were performed in kratom extracts. The effects on α-glucosidase and pancreatic lipase activities were investigated in kratom extracts and mitragynine. The LC-MS/MS analysis showed that the mitragynine, quercetin, and rutin contents from kratom extracts were different. The ethanol extract exhibited the highest total phenolic content (TPC), total flavonoid content (TFC), and total alkaloid content (TAC). Additionally, compared to methanol and aqueous extracts, the ethanol extract showed the strongest inhibition activity against α-glucosidase and pancreatic lipase. Compared with the anti-diabetic agent acarbose, mitragynine showed the most potent α-glucosidase inhibition, with less potent activity of pancreatic lipase inhibition. Analysis of α-glucosidase and pancreatic lipase kinetics revealed that mitragynine inhibited noncompetitive and competitive effects, respectively. Combining mitragynine with acarbose resulted in a synergistic interaction with α-glucosidase inhibition. These results have established the potential of mitragynine from kratom as a herbal supplement for the treatment and prevention of diabetes mellitus.

Blood Lead Levels among Non-Occupationally Exposed Pregnant Women in Southern Thailand.

Lead (Pb) is a heavy metal that is toxic to humans, especially children and pregnant women. In Thailand, guidelines exist to minimize lead exposure in pregnant women working in lead-related occupations. However, no guidelines exist for pregnant women who are not employed in these economic sectors. This cross-sectional study aimed to examine blood lead levels (BLLs) and related risk factors among 80 non-occupationally exposed pregnant women from the general population living in Nakhon Si Thammarat province, Southern Thailand. BLLs were determined by graphite furnace atomic absorption spectrophotometry. A validated questionnaire was adopted to interview participants which included demographic, consumer goods, supplement intake, and health factors. The mean BLL was 4.68 ± 1.55 µg/dL (95% CI 4.33-5.02) and 42.50% had BLLs ≥ 5 µg/dL. Higher education was the only demographic factor associated with BLLs ≥ 5 µg/dL (aOR 0.16, 95% CI 0.03-0.80, p = 0.027). Systolic blood pressure was also associated with BLLs ≥ 5 µg/dL (aOR 5.00, 95% CI 1.23-17.16, p = 0.023). However, consumer goods and supplement intake were not associated with BLLs. Our results indicate that pregnant women from the general population who were not in the risk exposure group had lead in their bodies. Except for education, demographics were not associated with pregnant women with BLLs. However, with health factors, even low BLLs had a small effect on systolic blood pressure. These data suggest a need for promoting health education and health interventions to prevent the dangers of lead exposure, especially for pregnant women and children.

Effects of Environmental Exposure to Cadmium and Lead on the Risks of Diabetes and Kidney Dysfunction.

Environmental exposure to cadmium (Cd) or lead (Pb) is independently associated with increased risks of type 2 diabetes, and chronic kidney disease. The aim of this study was to examine the effects of concurrent exposure to these toxic metals on the risks of diabetes and kidney functional impairment. The Cd and Pb exposure levels among study subjects were low to moderate, evident from the means for blood concentrations of Cd and Pb ([Cd]b and [Pb]b) of 0.59 µg/L and 4.67 µg/dL, respectively. Of 176 study subjects (mean age 60), 71 (40.3%) had abnormally high fasting plasma glucose levels. Based on their [Cd]b and [Pb]b, 53, 71, and 52 subjects were assigned to Cd and Pb exposure profiles 1, 2, and 3, respectively. The diagnosis of diabetes was increased by 4.2-fold in those with an exposure profile 3 (p = 0.002), and by 2.9-fold in those with the estimated glomerular filtration (eGFR) ≤ 60 mL/min/1.73 m2 (p = 0.029). The prevalence odds ratio (POR) for albuminuria was increased by 5-fold in those with plasma glucose levels above kidney threshold of 180 mg/dL (p = 0.014), and by 3.1-fold in those with low eGFR) (p = 0.050). Collectively, these findings suggest that the Cd and Pb exposure profiles equally impact kidney function and diabetes risk.

The construction and validation of a lead exposure screening tool for pregnant women in Thailand (ThaiL8Is).

Objectives: To construct, validate, and implement a new screening tool for lead exposure in Thai pregnant women. Methods: A cross-sectional study that included three processes: screening tool development, validation, and implementation. The participants were pregnant women who had received antenatal care at district health promotion hospitals. There were 100 pregnant women in Nakhon Si Thammarat province during the validation process, and 30 pregnant women in Phang Nga province during the implementation process. Blood lead levels (BLLs) were analysed by atomic absorption spectrophotometry. The sensitivity and specificity of the screening instrument, as well as the Area Under the Curve (AUC), demonstrate its validity. Results: There were 80 BLL-related items found through the collection of primary and secondary data and examined for validity and inter-rater reliability by five experts. Six items were excluded because the values were less than the criteria set. Seventy-four items remained with the Item Content Validity Index (I-CVI) = 0.80-1.00, the Content Validity Index Average (S-CVI/Ave) = 0.91, and Kappa scores = 0.76-1.00. After using 74 items collected on pregnant women, only 31 items were included in the validation process. Following that, the pooled eight items with cut-off point scores of 1 had the highest validity, which included systolic blood pressure, diastolic blood pressure, urine sugar, haemoglobin level, occupation, drinking coffee, using chemical products, and education level (ThaiL8Is). The ThaiL8Is in the validation process yielded sensitivity = 80.9%, specificity = 69.8%, and an AUC (95%CI) = 0.78 (0.69-0.87). The implementation process has confirmed the validity of the screening tool; sensitivity = 78.9%, specificity = 81.8%, and the AUC (95%CI) = 0.80 (0.63-0.97). Conclusions: The ThaiL8Is a valid screening tool for Thai pregnant women. ThaiL8Is' sensitivity in detecting the risk groups for lead exposure can be enhanced by a combination of biochemical markers used in routine prenatal screening. It can be used to screen pregnant women for early indicators of lead exposure prior to a blood lead test.

Enhancing Toxicology Achievement by the VARK and the GRSLSS-mixed Models in Team-Based Learning.

Toxicology is needed to implement in the occupational health and safety (OHS) curriculum. Teaching toxicology is very challenging as its multidisciplinary science. Keeping students engaged in learning is a difficult issue when introducing solely theoretical framework. To enhance student performance, educators need to be aware of different learning styles and teach students accordingly. This study aimed to examine preferred learning styles and to further investigate the impact of learning style on team allocation and the effectiveness of team-based learning (TBL) in toxicology. A cross-sectional study of OHS students was performed. The visual, aural, reading/writing, and kinesthetic (VARK) learning style questionnaire and the Grasha-Reichmann Student Learning Styles Scale (GRSLSS), which identifies independent, dependent, collaborative, participant, competitive, and avoidant learning styles, were used with 101 study participants. After classification, participants studied three aspects of toxicology in three respective situations: (i) individual learning, (ii) TBL with students of the same VARK learning style, and (iii) TBL with students of varying VARK learning styles. Afterward, participants wrote a test on each of the aspects. The dominant VARK and GRSLSS learning styles were reading/writing (33.33%) and collaborative (50.00%), respectively. The participants achieved the highest test scores (88.31%) when they studied in a team with the various VARK styles, followed by studying in a team with the same VARK style (83.43%). Individual learning produced the lowest average score (69.79%). The results of this study suggest that creating a successful heterogeneity team based on the preferred learning styles is an effective teaching method in toxicology. It might be useful to toxicology educators and research studies from a wide range of disciplines to enhance student performance.

Structure-activity relationship and in vitro inhibition of human cytochrome CYP2A6 and CYP2A13 by flavonoids.

Cigarette smoking is one of the major risk factors of various diseases including respiratory diseases and lung cancer. While the liver-specific CYP2A6 is associated with the nicotine clearance and smoking addiction, the metabolic activation of the tobacco-specific nitrosamine by lung-specific CYP2A13 can lead to lung tumorigenesis.It has been reported that inhibition of CYP2A6 and CYP2A13 enzymes by flavonoids constituents could be an aids in smoking cessation. This study demonstrates the inhibition activity of kaempferol and myricetin and the structure-function relationship of these two flavonoids and previously isolated flavonoids from Vernonia cinerea and Pluchea indica against both enzymes.Kaempferol could inhibit CYP2A6 with Kic value of 1.77 ± 0.47 µM while inhibit CYP2A13 with Kic value of 0.12 ± 0.01 µM. Myricetin could inhibit CYP2A6 with Kic value of 4.06 ± 0.52 µM while inhibit CYP2A13 with Kic value of 1.88 ± 0.03 µM.Molecular docking indicated that CYP2A13 enzyme has strong hydrophobic interaction with ring B of flavonoids compared to CYP2A6 enzyme. The presence of the hydroxyl group at C3 position of ring C and the hydroxyl group at C5' of ring B affected inhibitory activity on both enzymes.

Anti-proliferative effect of 8α-tigloyloxyhirsutinolide-13-O-acetate (8αTGH) isolated from Vernonia cinerea on oral squamous cell carcinoma through inhibition of STAT3 and STAT2 phosphorylation.

BACKGROUND: The high mortality rate of oral cancers has stimulated the search for effective herbal medicines and their pharmacological targets. Vernonia cinerea, a perennial tropical herb, is wildly used as a traditional folk medicine for treatment of intestinal diseases and various skin diseases in addition to possessing anti-cancer activity. However, the effect of 8α-tigloyloxyhirsutinolide-13-O-acetate (8αTGH) as a major sesquiterpene lactone compound found in V. cinerea and the underlying mechanism of its action on oral cancer cells remains unknown. PURPOSE: To investigate the anti-cancer activity of 8αTGH extracted from V. cinerea and the underlying mechanism of its action in oral cancer cells. METHODS: The anti-proliferative effect of 8αTGH on oral squamous cell carcinoma (HSC4) and lung carcinoma (A549) was determined using the SRB colorimetric method. The molecular mechanism of 8αTGH was explored using kinase inhibitors, followed by Western blotting or RT-qPCR. Flow cytometry and Western blotting were used to assess cell cycle arrest. RESULTS: 8αTGH inhibited cancer cell growth more effectively on HSC4 than A549 and was much less effective on tested normal oral cells. 8αTGH inhibited STAT3 phosphorylation on both cancer cells. Notably, 8αTGH was able to suppress the constantly activated STAT2 found only in HSC4. The STAT2 inhibition by 8αTGH consequently caused down-regulation of ISG15 and ISG15 conjugates. As a result, decreased expression of CDK1/2 and Cyclin B1 was detected leading to G2/M cell cycle arrest. CONCLUSION: 8αTGH isolated from V. cinerea preferentially inhibits the proliferation of oral cancer cells by causing G2/M cell cycle arrest via inhibition of both STAT3 and STAT2 phosphorylation. The results provide molecular bases for developing 8αTGH as a drug candidate or a complementary treatment of oral cancer.

Effects of Vernonia cinerea Compounds on Drug-metabolizing Cytochrome P450s in Human Liver Microsomes.

Vernonia cinerea has been widely used in traditional medicines for various diseases and shown to aid in smoking abstinence and has anticancer properties. V. cinerea bioactive compounds, including flavonoids and hirsutinolide-type sesquiterpene lactones, have shown an inhibition effect on the nicotine-metabolizing cytochrome P450 2A6 (CYP2A6) enzyme and hirsutinolides reported suppressing cancer growth. In this study, V. cinerea ethanol extract and its bioactive compounds, including four flavonoids and four hirsutinolides, were investigated for an inhibitory effect on human liver microsomal CYPs 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, and 3A4 using cocktail inhibition assays combined with LC-MS/MS analysis. Among tested flavonoids, chrysoeriol was more potent in inhibition on CYP2A6 and CYP1A2 than other liver CYPs, with better binding efficiency toward CYP2A6 than CYP1A2 (Ki values in competitive mode of 1.93 ± 0.05 versus 3.39 ± 0.21 µM, respectively). Hirsutinolides were prominent inhibitors of CYP2A6 and CYP2D6, with IC50 values of 12-23 and 15-41 µM, respectively. These hirsutinolides demonstrated time-dependent inhibition, an indication of mechanism-based inactivation, toward CYP2A6. Quantitative prediction of microsomal metabolism of these flavonoids and hirsutinolides, including half-lives and hepatic clearance rate, was examined. These findings may have implications for further in vivo studies of V. cinerea. Copyright © 2017 John Wiley & Sons, Ltd.

Inhibition of human cytochromes P450 2A6 and 2A13 by flavonoids, acetylenic thiophenes and sesquiterpene lactones from Pluchea indica and Vernonia cinerea.

The human liver cytochrome P450 (CYP) 2A6 and the respiratory CYP2A13 enzymes play role in nicotine metabolism and activation of tobacco-specific nitrosamine carcinogens. Inhibition of both enzymes could offer a strategy for smoking abstinence and decreased risks of respiratory diseases and lung cancer. In this study, activity-guided isolation identified four flavonoids 1-4 (apigenin, luteolin, chrysoeriol, quercetin) from Vernonia cinerea and Pluchea indica, four hirsutinolide-type sesquiterpene lactones 5-8 from V. cinerea, and acetylenic thiophenes 9-11 from P. indica that inhibited CYP2A6- and CYP2A13-mediated coumarin 7-hydroxylation. Flavonoids were most effective in inhibition against CYP2A6 and CYP2A13, followed by thiophenes, and hirsutinolides. Hirsutinolides and thiophenes exhibited mechanism-based inhibition and in irreversible mode against both enzymes. The inactivation kinetic KI values of hirsutinolides against CYP2A6 and CYP2A13 were 5.32-15.4 and 0.92-8.67 µM, respectively, while those of thiophenes were 0.11-1.01 and 0.67-0.97 µM, respectively.