The relationship between characteristics of gait disturbance and injury patterns of the corticospinal tract and corticoreticular pathway in post-stroke patients: A case series of 3 patients.

RATIONALE: Corticospinal tract (CST) and corticoreticular pathway (CRP) injury patterns (i.e., the continuity of the nerve fibers) are associated with gait disturbance in post-stroke patients. In this case series study, we examined the case of 3 patients with different CST and CRP injury patterns and analyzed the characteristics of gait disturbance in each patient. PATIENT CONCERNS: Patient 1 (P1) was a 73-year-old woman who presented with paralysis of the right upper and lower extremities due to a left lacunar infarction. Patient 2 (P2) was a 41-year-old man who presented with paralysis of the right upper and lower extremities due to a left putamen hemorrhage. Patient 3 (P3) was a 57-year-old man who presented with paralysis of the left upper and lower extremities due to a right putamen hemorrhage. DIAGNOSIS: In P1, the CRP in the affected hemisphere was intact, but the CST was discontinuous. In P2, the CST in the affected hemisphere was intact, but the CRP was discontinuous. P3 was discontinuous in both CST and CRP in the affected hemisphere. OUTCOMES: Over time, all 3 patients improved to the level of gait independence, but they exhibited different gait patterns. Among them, P3 showed a markedly abnormal gait pattern that included spatiotemporal gait asymmetry, lateral shift of the trunk, and hip hiking. LESSONS: This case series study demonstrated that even if both the CST and CRP were injured, gait recovered to some extent (i.e., independent level-ground gait), but the abnormal gait pattern might remain remarkable.

Availability of aldo-keto reductase 1C3 and ATP-binding cassette B1 as therapeutic targets for alleviating paclitaxel resistance in breast cancer MCF7 cells.

Paclitaxel (PTX) is frequently utilized for the chemotherapy of breast cancer, but its continuous treatment provokes hyposensitivity. Here, we established a PTX-resistant variant of human breast cancer MCF7 cells and found that acquiring the chemoresistance elicits a remarkable up-regulation of aldo-keto reductase (AKR) 1C3. MCF7 cell sensitivity to PTX toxicity was increased by pretreatment with AKR1C3 inhibitor and knockdown of this enzyme, and decreased by its overexpression, inferring a crucial role of AKR1C3 in the development of PTX resistance. The PTX-resistant cells were much less sensitive to 4-hydroxy-2-nonenal and acrolein, cytotoxic reactive aldehydes derived from ROS-mediated lipid peroxidation, compared with the parental cells. Additionally, the resistant cells lowered levels of 4-hydroxy-2-nonenal formed during PTX treatment, which was mitigated by pretreating with AKR1C3 inhibitor, suggesting that AKR1C3 procures the chemoresistance through facilitating the metabolism of the cytotoxic aldehyde. The gain of PTX resistance additively promoted the aberrant expression of an ATP-binding cassette (ABC) transporter ABCB1 among the ABC transporter isoforms. The combined treatment with AKR1C3 and ABCB1 inhibitors overcame the PTX resistance and cross-resistance to another taxane-based drug docetaxel. Collectively, combined treatment with AKR1C3 and ABCB1 inhibitors may exert an overcoming effect of PTX resistance in breast cancer.

Enhancement of Endothelial Barrier Permeability by Mitragynine.

Persistent inhalation of mitragynine (MG), a major alkaloid in the leaves of Mitragyna speciosa, causes various systemic adverse effects such as seizure, diarrhea and arthralgias, but its toxicity to endothelial cells and effects on barrier function of the cells are poorly understood. In this study, we compared toxicities of MG and mitraphylline, another constituent of the leaves, against human aortic endothelial (HAE), bronchial BEAS-2B, neuronal SK-N-SH, hepatic HepG2, kidney HEK293, gastric MKN45, colon DLD1, lung A549, breast MCF7 and prostate LNCaP cells, and found that MG, but not mitraphylline, shows higher toxicity to HAE cells compared to the other cells. Forty-eight-hours incubation of HAE cells with a high concentration of MG (60 µM) provoked apoptotic cell death, which was probably due to signaling through enhanced reactive oxygen species (ROS) generation and resultant caspase activation. Treatment of the cells with MG at sublethal concentrations less than 20 µM significantly lowered transendothelial electrical resistance and elevated paracellular permeability, without affecting the cell viability. In addition, the MG-elicited lowering of the resistance was abolished by a ROS inhibitor N-acetyl-L-cysteine and augmented by H2O2 and 9,10-phenanthrenequinone, which generates ROS through its redox cycle. These results suggest the contribution of ROS generation to the increase in endothelial barrier permeability.