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- Ge, CT, et al.
(författare)
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Neurokinin-1 receptor is an effective target for treating leukemia by inducing oxidative stress through mitochondrial calcium overload
- 2019
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 116:39, s. 19635-19645
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Tidskriftsartikel (refereegranskat)abstract
- Substance P (SP) regulates multiple biological processes through its high-affinity neurokinin-1 receptor (NK-1R). While the SP/NK-1R signaling axis is involved in the pathogenesis of solid cancer, the role of this signaling pathway in hematological malignancy remains unknown. Here, we demonstrate that NK-1R expression is markedly elevated in the white blood cells from acute myeloid leukemia patients and a panel of human leukemia cell lines. Blocking NK-1R induces apoptosis in vitro and in vivo via increase of mitochondrial reactive oxygen species. This oxidative stress was triggered by rapid calcium flux from the endoplasmic reticulum into mitochondria and, consequently, impairment of mitochondrial function, a mechanism underlying the cytotoxicity of NK-1R antagonists. Besides anticancer activity, blocking NK-1R produces a potent antinociceptive effect in myeloid leukemia-induced bone pain by alleviating inflammation and inducing apoptosis. These findings thus raise the exciting possibility that the NK-1R antagonists, drugs currently used in the clinic for preventing chemotherapy-induced nausea and vomiting, may provide a therapeutic option for treating human myeloid leukemia.
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- Peng, WC, et al.
(författare)
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Muscular Morphomechanical Characteristics After an Achilles Repair
- 2019
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Ingår i: Foot & ankle international. - : SAGE Publications. - 1944-7876 .- 1071-1007. ; 40:5, s. 568-577
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of the study was to compare the morphomechanical and functional characteristics during maximal isometric, concentric, and eccentric contractions in the legs of patients that underwent unilateral Achilles tendon repair with those in their noninjured control legs. Methods: Twenty participants (median age = 38.2 years; range, 21.1-57.3 years) who underwent Achilles repair between 3 and 12 months ago were recruited with the following measures: (1) mechanical stiffness of the aponeurosis and (2) electromyography and medial gastrocnemius fascicle angle and length, standing muscle and tendon length, and height of heel rise with isometric contraction. Results: Compared to the noninjured legs, the repaired legs showed less resting fascicle length, standing muscle length, isometric plantarflexion torque, and heel raise distance ( Ps ranged between .044 and <.001). During the concentric and eccentric phases of the raising and lowering test, the repaired legs demonstrated less fascicle length ( P ≤ .028) but greater tendinous tissue length ( Ps ranged between .084 and <.001) and fascicle angle ( Ps ranged between .247 and .008) and fewer change magnitudes of the fascicle length and tendinous tissue length ( P ≤ .003). The change magnitudes of the morphological characteristics showed correlations with the torque or distance. Conclusion: Selecting the appropriate surgical repair and rehabilitation for Achilles tendon ruptures is recommended for restoring the length and mechanical strength of the muscle-tendon unit of plantar-flexion muscles. Level of Evidence: Level III, comparative study.
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