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Objective: To observe the therapeutic effect of sinew-regulating bone-setting manipulations for knee osteoarthritis (KOA) model rabbits and its impacts on the chondrocyte apoptosis rate and the levels of interleukin (IL)-1β and nitric oxide (NO). Methods: According to the random number table method, 30 New Zealand white rabbits were divided into a normal group (n=9) and a modeling group (n=21). Rabbits in the modeling group were used to establish KOA models with the modified Hulth method. At the 8th week, three rabbits were sacrificed to verify the model and the remaining 18 rabbits were randomly divided into a model group (n=9) and an intervention group (n=9). Rabbits in the normal group and model group were bred routinely without any intervention. Rabbits in the intervention group were treated with the sinew-regulating bone-setting manipulations, 10 min/time, once every other day for a total of 20 times. The Lequesne MG knee function rating was used to evaluate the behavioral differences of the rabbits in each group. The Pelletier score was used to evaluate the general changes of the rabbits. The Mankin score was used to evaluate the pathology of knee cartilages. The enzyme-linked immunosorbent assay and nitrate reductase methods were used to determine the levels of IL-1β and NO in serum and synovial fluid of each group, respectively. In situ terminal deoxynucleotidyl transferase-mediated nick and labeling method was used to determine the apoptosis of chondrocytes in each group. Results: Compared with the normal group, the scores of Lequesne MG, Pelletier and Mankin, and the levels of IL-1β and NO in the model group were increased (P<0.05), which indirectly indicated the success of the model. Compared with the model group, the scores of Lequesne MG, Pelletier and Mankin, IL-1β and NO levels, and chondrocyte apoptosis rate of the intervention group were decreased, and the differences were statistically significant (P<0.05). Conclusion: The sinew-regulating bone-setting manipulations can reduce the levels of IL-1β, NO, and chondrocyte apoptosis rate, and delay the articular cartilage degeneration, therefore, having a good therapeutic effect on KOA.
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Despite the success of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in the treatment of non-small cell lung cancer (NSCLC) harboring EGFR-activating mutations, intrinsic or acquired resistance remains the major obstacle to long-term disease remission. Defective autophagy has been reported as an EGFR-TKI resistance mechanism. However, how EGFR regulate autophagic flux are still not fully understood. Here we found that EGFR-stimulated phosphorylation of SQSTM1 at tyrosine 433 induces dimerization of its UBA domain, which disturbs the sequestration function of SQSTM1 and causes autophagic flux blocking. SAH-EJ2, a staple optimized EGFR-derived peptide, showed enhanced in vitro and in vivo antitumor activity against NSCLC than the prototype regardless of EGFR mutation status. Mechanistically, SAH-EJ2 disrupts the EGFR-SQSTM1 interaction and protects against EGFR-induced SQSTM1 phosphorylation, which hinders the dimerization of the SQSTM1 UBA domains and restores SQSTM1 cargo function. Moreover, SAH-EJ2 suppresses EGFR activity by blocking its dimerization and reducing its protein stability, which reciprocally activates the core autophagy machinery. Our observations reveal that disturbing the EGFR-SQSTM1 interaction by SAH-EJ2 confers a potential strategy in the treatment of NSCLC through suppressing EGFR signalling and activating autophagy simultaneously.
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Autofagia , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Regulación Neoplásica de la Expresión Génica , Neoplasias Pulmonares/tratamiento farmacológico , Fragmentos de Péptidos/farmacología , Proteína Sequestosoma-1/antagonistas & inhibidores , Animales , Antineoplásicos/farmacología , Apoptosis , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Proliferación Celular , Resistencia a Antineoplásicos , Receptores ErbB/antagonistas & inhibidores , Receptores ErbB/genética , Receptores ErbB/metabolismo , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Mutación , Inhibidores de Proteínas Quinasas/farmacología , Multimerización de Proteína , Proteína Sequestosoma-1/metabolismo , Transducción de Señal , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
<p><b>OBJECTIVE</b>To observe amplitude changes of low frequency fluctuation in brain spontaneous nervous activities induced by needling at Hand Taiyin Lung Channel, and to preliminarily explore the possible brain function network of Hand Taiyin Lung Channel.</p><p><b>METHODS</b>By using functional magnetic resonance imaging (fMRI), 16 healthy volunteers underwent resting-state scanning (R1) and scanning with retained acupuncture at Hand Taiyin Lung Channel (acupuncture, AP). Data of fMRI collected were statistically calculated using amplitude of low frequency fluctuations (ALFF).</p><p><b>RESULTS</b>Under R1 significantly enhanced ALFF occurred in right precuneus, left inferior parietal lobule, bilateral superior temporal gyrus, bilateral middle frontal gyrus, left superior frontal gyrus, left inferior frontal gyrus, left medial frontal gyrus. Under AP significantly enhanced ALFF occurred in right precuneus, bilateral superior frontal gyrus, cerebellum, bilateral middle frontal gyrus, right medial frontal gyrus, and so on. Compared with R1, needing at Hand Taiyin Lung Channel could significantly enhance ALFF in right gyrus subcallosum and right inferior frontal gyrus. Significant decreased ALFF appeared in right postcentral gyrus, left precuneus, left superior temporal gyrus, left middle temporal gyrus, and so on.</p><p><b>CONCLUSION</b>Needing at Hand Taiyin Lung Channel could significantly change fixed activities of cerebral cortex, especially in right subcallosal gyrus, right inferior frontal gyrus, and so on.</p>
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Humanos , Terapia por Acupuntura , Encéfalo , Fisiología , Mapeo Encefálico , Imagen por Resonancia MagnéticaRESUMEN
<p><b>OBJECTIVE</b>To observe the effect of acupuncture at the whole points of Hand Jueyin pericardium meridian on the amplitude of low frequency fluctuations (ALFF) of healthy people in resting state (R1) functional magnetic resonance imaging (fMRI).</p><p><b>METHODS</b>Totally 16 healthy subjects received structure scan of T1 and T2. Then two fMRI scans were conducted for each participant. fMRI included the resting-state scan (R1; the scanning time was 8 min 6 s), the stimulating-acupoint scan (AP; the scanning time was 8 min 6 s). fMRI data acquisition from structure scanning and function scanning were processed with format conversion and statistical analysis.</p><p><b>RESULTS</b>Under R1 state, brain regions with activated ALFF signals included bilateral superior frontal gyrus, medial frontal gyrus, middle occipital gyrus, precuneus, superior temporal gyrus, and cingulate gyrus. Under the AP state, brain regions with activated ALFF signals were bilateral superior frontal gyrus, medial frontal gyrus, middle temporal gyrus, left fusiform gyrus, precuneus, posterior cingulate, and declivis. Compared with R1 state, obvious difference of ALFF signal areas of the brain caused by acupuncture at pericardium were: bilateral cuneus, precuneus, left posterior cingulate gyrus, right middle occipital gyrus, and right occipital lingual gyrus.</p><p><b>CONCLUSION</b>Acupuncture at the whole points of Hand Jueyin pericardium meridian could significantly change inherent activity states of the cerebral cortex, especially in bilateral superior frontal gyrus, medial frontal gyrus, and precuneus.</p>
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Humanos , Acupuntura , Puntos de Acupuntura , Encéfalo , Fisiología , Mapeo Encefálico , Lóbulo Frontal , Imagen por Resonancia Magnética , Métodos , PericardioRESUMEN
<p><b>OBJECTIVE</b>To investigate the relationship of the acupoint and its functional location in the brain.</p><p><b>METHODS</b>Ten healthy participants were examined with the resting state functional magnetic resonance imaging (fM-RI). The scanning includes the resting state 1 (R 1), acupuncture stimulating (AP) Neiguan (PC 6) and the resting state 2 (R 2). All data were analyzed with the amplitude of low frequency fluctuations (ALFF).</p><p><b>RESULTS</b>1) During the R1, the regions with active signal on the ALFF contained bilateral superior frontal gyrus, medial frontal gyrus and some part of cerebellum (including right declive, culme, tonsil and left uvula), as well as left precuneus, right superiour temporal gyrus. 2) As for AP, the active regions with higher ALFF were bilateral superior frontal gyrus and right cuneus, as well as left middle frontal gyrus, declivis and right semi-lunar lobule. 3) The main difference on ALFF between R1 and AP appeared within bilateral cingulated gyrus and declivis, left lingualgurus, and cuneus, as well as right precuneus, fusiform gyrus, superior frontal gyrus, medial frontal gyrus and superior temporal gyrus, etc.</p><p><b>CONCLUSION</b>After acupuncture stimulating the left Neiguan (PC 6), the active regions on ALFF are detected on bilateral cingulated gyrus, right superior frontal gyrus and medial frontal gyrus, as well as bilateral declivis and left lingual gurus, etc. These regions have the close relationship with the mental disorder and nervous diseases, which might be the possible neural mechanism of acupuncture stimulating Neiguan (PC 6) for treating some of related mental disorder and nervous diseases.</p>