Increased bisphenol A levels in Thai children and adolescents with type 1 diabetes mellitus.

BACKGROUND: The incidence of type 1 diabetes mellitus (T1DM) in children and adolescents continues to increase worldwide. The reason for this is unclear. In addition to the role of genetics, bisphenol A (BPA) has been investigated as a possible causal factor for T1DM. This study aimed to determine the correlation between urinary BPA levels and T1DM in Thai children and adolescents. METHODS: A cross-sectional study was conducted in T1DM patients who were followed at the endocrinology clinic at King Chulalongkorn Memorial Hospital from December 2018 to December 2019 and age-matched healthy controls. Urinary BPA levels were analyzed by high-performance liquid chromatography and adjusted by urine creatinine. Anthropometric data were measured in all participants and clinical data were collected for the T1DM patients. All participants completed a questionnaire regarding possible BPA exposures. Multivariate logistic regression analysis was used to estimate the adjusted odds ratio for T1DM. RESULTS: Seventy-five T1DM patients and 113 age-matched controls were included in the study. The mean age for T1DM and control groups were 14.8 ± 5.7 and 14.4 ± 6.2 years, respectively. The T1DM group had a significantly higher median (interquartile range) level of adjusted urinary BPA compared to the control (31.50 [7.87, 69.45] vs 10.1 [0, 54.01] µg/g creatinine, P = 0.02). Urinary BPA of 17 µg/g creatinine or more was significantly associated with TIDM, with adjusted odds ratio (95% Confident interval, CI) of 2.38 (1.27, 4.44), P = 0.006. CONCLUSIONS: Higher urinary BPA level is one of the possible risk factors for T1DM.

Dehydrozingerone, a Curcumin Analog, as a Potential Anti-Prostate Cancer Inhibitor In Vitro and In Vivo.

Curcumin (Cur) exhibits biological activities that support its candidacy for cancer treatment. However, there are limitations to its pharmacological effects, such as poor solubility and bioavailability. Notably, the use of Cur analogs has potential for addressing these limitations. Dehydrozingerone (DZG) is a representative of the half-chemical structure of Cur, and many reports have indicated that it is anticancer in vitro. We, therefore, have hypothesized that DZG could inhibit prostate cancer progression both in vitro and in vivo. Results revealed that DZG decreased cell proliferation of rat castration-resistant prostate cancer, PLS10 cells, via induction of the cell cycle arrest in the G1 phase in vitro. In the PLS10 xenograft model, DZG significantly decreased the growth of subcutaneous tumors when compared to the control via the inhibition of cell proliferation and angiogenesis. To prove that DZG could improve the limitations of Cur, an in vivo pharmacokinetic was determined. DZG was detected in the serum at higher concentrations and remained up to 3 h after intraperitoneal injections, which was longer than Cur. DZG also showed superior in vivo tissue distribution than Cur. The results suggest that DZG could be a candidate of the Cur analog that can potentially exert anticancer capabilities in vivo and thereby improve its bioavailability.

Chemosensitizing effects of synthetic curcumin analogs on human multi-drug resistance leukemic cells.

Curcumin analogs were synthesized and their multi-drug resistance (MDR) reversing properties were determined in human MDR leukemic (K562/Adr) cells. Four analogs, 1,7-bis-(3,4-dimethoxy-phenyl)-hepta-1,6-diene-3,5-dione (1J), 2,6-bis-(4-hydroxy-3-methoxy-benzylidene)-cyclohexanone (2A), 2,6-bis-(3,4-dihydroxy-benzylidene)-cyclohexanone (2F) and 2,6-bis-(3,4-dimethoxy-benzylidene)-cyclohexanone (2J) markedly increased the sensitivity of K562/Adr cells to paclitaxel (PTX) for 8-, 2-, 8- and 16- folds, respectively and vinblastine (Vin) for 5-, 3-, 12- and 30- folds, respectively. The accumulation of P-gp substrates, Calcein-AM, Rhodamine 123 and Doxorubicin, was significantly increased by 1J (up to 6-, 11- and 22- folds, respectively) and 2J (up to 7-, 12- and 17- folds, respectively). Besides 2A, 2F and 2J dramatically decreased P-gp expression in K562/Adr cells. These results could be summarized in the following way. Analog 1J inhibited only P-gp function, while 2A and 2F inhibited only P-gp expression. Interestingly, 2J exerts inhibition of both P-gp function and expression. The combination index (CI) of combination between 2J and PTX (0.09) or Vin (0.06) in K562/Adr cells indicated strong synergistic effects, which likely due to its MDR reversing activity. Moreover, these analogs showed less cytotoxicity to peripheral mononuclear cells (human) and red blood cells (human and rat) suggesting the safety of analogs for further animal and clinical studies.