Inflammatory bowel disease (IBD) is a notable health problem and may considerably affect the quality of human life. Previously, the protective roles of tryptanthrin (TRYP) against dextran sulfate sodium (DSS) induced colitis has been proved, but the concrete mechanism remained elusive. It has been suggested that TRYP could diminish the weight loss and improve the health conditions of mice with DSS induced colitis. Hematoxylin and eosin staining revealed that TRYP could improve the histopathological structure of the colon tissue. Two signaling pathways (TNF-α/NF-κBp65 and IL-6/STAT3) were investigated using immunochemistry and western blot. The detected concentrations of the two cytokines TNF-α and IL-6 showed that their levels decreased after TRYP treatment of the colitis. The protein expression level of NF-κBp65 in cytoplasm increased after TRYP treatment of the induced colitis. However, the protein level of NF-κBp65 in the nucleus decreased after administration of TRYP. The expression level of IκBα, the inhibitory protein of NF-κBp65, was tested and the results suggested that TRYP could inhibit the degradation of IκBα. The phosphorylation level of STAT3 was inhibited by TRYP and the expression level of STAT3 and p-STAT3 decreased after administration of TRYP. We conclude that TRYP improves the health condition of mice with DSS induced colitis by regulating the TNF-α/NF-κBp65 and IL-6/STAT3 signaling pathways via inhibiting the degradation of IκBα and the phosphorylation of STAT3.

Polypharmacy, defined as the use of 5 or more medications is associated with multiple adverse outcomes in older adults, including falls and slow gait velocity. However, the relationship between polypharmacy and cortical control of locomotion has not been reported. The purpose of this study was to examine the relationship between polypharmacy and activation patterns in the prefrontal cortex (PFC), a brain region involved in higher order control of locomotion during attention-demanding conditions. Using Functional Near Infrared Spectroscopy (fNIRS) to quantify PFC oxygenated hemoglobin (HbO₂) levels, we performed a cross sectional analysis of 325 community dwelling adults age ≥65 years, and examined HbO₂ levels during single tasks (Single-Task-Walk (STW), (talking, cognitive interference (Alpha)) and Dual-Task Walk (DTW)). The prevalence of polypharmacy was 33% (n = 104) amongst the 325 participants (mean age 76.4 ± 6.7 years, 56% women). Among the 221 participants with no polypharmacy there was an increase in HbO₂ levels from STW to DTW (estimate = -0.625; p = <0.001) and from Alpha to DTW (estimate=-0.079; p = 0.031). Polypharmacy status, however, moderated the change in HbO₂ levels comparing the two single tasks to the dual-task walking condition. Specifically, the presence of polypharmacy was associated with an attenuated increase in HbO₂ levels from STW to DTW (estimate = 0.149; p = 0.027) and with a decline in HbO₂ levels from Alpha to DTW (estimate = 0.169; p = 0.009) after adjustments for potential confounders including medical comorbidities and the use of high-risk medications. The results of this study further support the need for clinicians to reduce polypharmacy in older adults, given its significant association with the PFC hemodynamic response during attention-demanding locomotion.

Corilagin is the primary active component of the Euphorbia phyllanthus plant and has significant anti‑cancer properties. However, the biological effects and mechanisms of corilagin on acute myeloid leukemia (AML) have not been clarified. The Cell Counting Kit‑8 and Carboxyfluorescein Diacetate Succinimidyl Ester assay results showed that corilagin significantly inhibited proliferation of the AML cell line HL‑60 in a time‑ and dose‑dependent manner. Western blotting and flow cytometry analysis were performed to determine the levels of apoptosis in HL‑60 cells. The protein levels of cleaved caspase‑3 and Bak were upregulated, while Bcl‑xl was downregulated in cells treated with corilagin. The percentage of early‑ and late‑stage apoptotic cells increased following corilagin treatment in a dose‑dependent manner, indicating that the intrinsic mitochondrial apoptosis pathway was activated by corilagin. Simultaneously, western blotting and immunofluorescence results revealed that autophagy was suppressed; this was accompanied by a decrease in light chain 3‑II (LC3‑II) conversion and autophagosomes. MicroRNA (miRNA/miR) profile analysis showed that corilagin elevated the expression of the tumor suppressor miR‑451, while the mRNA and protein levels of high mobility group protein B1 (HMGB1), the target of miR‑451, decreased following exposure to corilagin. Knockdown of miR‑451 decreased the downregulation of HMGB1 caused by corilagin, indicating negative regulation of HMGB1 by miR‑451 during corilagin treatment. Furthermore, knockdown of miR‑451 also attenuated corilagin‑induced proliferation inhibition of HL‑60 cells, implying that miR‑451 was essential for the proliferation inhibitory effect of corilagin. In conclusion, these results indicated that corilagin induced apoptosis and inhibited autophagy in HL‑60 cells by regulating the miR‑451/HMGB1 axis, and corilagin may be a novel therapeutic drug for the treatment of AML.