This review summarizes the anti-depressant mechanisms of repetitive transcranial magnetic stimulation in preclinical studies,including anti-inflammatory effects mediated by activation of nuclear factor-E2-related fact...This review summarizes the anti-depressant mechanisms of repetitive transcranial magnetic stimulation in preclinical studies,including anti-inflammatory effects mediated by activation of nuclear factor-E2-related factor 2 signaling pathway,anti-oxidative stress effects,enhancement of synaptic plasticity and neurogenesis via activation of the endocannabinoid system and brain derived neurotrophic factor signaling pathway,increasing the content of monoamine neurotransmitters via inhibition of Sirtuin 1/monoamine oxidase A signaling pathway,and reducing the activity of the hypothalamic-pituitary-adrenocortical axis.We also discuss the shortcomings of transcranial magnetic stimulation in preclinical studies such as inaccurate positioning,shallow depth of stimulation,and difficulty in elucidating the neural circuit mechanism up-and down-stream of the stimulation target brain region.展开更多
The purpose of this study was to determine the associations between urinary estradiol (E2) metabolite concentration and medial knee loading with radiographic disease severity in middle aged women with initial stage kn...The purpose of this study was to determine the associations between urinary estradiol (E2) metabolite concentration and medial knee loading with radiographic disease severity in middle aged women with initial stage knee osteoarthritis (OA). Women presenting with knee pain were recruited into a cross-sectional correlation study (KOA, n = 9, age = 52 ± 4 yrs). Self report menstrual history, the Modified Baecke Questionnaire and the Knee Injury and Osteoarthritis Outcome Score (KOOS) subjective data were collected. A fasting blood sample (follicle stimulating hormone (FSH) and Tumor Necrosis Factor-α (TNF-α)), and urine catch (16α-hydroxyestrone and 2-hydroxyestrone) were collected. Gait analysis using an 8-camera motion analysis system assessed internal knee varus moment and foot progression angle. Pearson Product moments tested for associations between urinary 16α-hydroxyestrone and 2-hydroxyestrone, TNF-α, medial knee loading, and radiographic disease severity (Kellgren/Lawrence (K/L) radiographic score). Significant correlations were found within the hormonal biomarkers (r = 0.94, p p p = 0.31). No correlations were found for radiographic disease severity or TNF-α. The lack of association between hormonal and biomechanical variables could be due to large variability of the E2 metabolites seen in the menopause transition and the limited structural changes of initial staged knee OA.展开更多
Background:The transforming growth factor-β(TGF-β)pathway plays a pivotal role in inducing epithelial-mesenchymal transition(EMT),which is a key step in cancer invasion and metastasis.However,the regulatory mechanis...Background:The transforming growth factor-β(TGF-β)pathway plays a pivotal role in inducing epithelial-mesenchymal transition(EMT),which is a key step in cancer invasion and metastasis.However,the regulatory mechanism of TGF-βin inducing EMT in colorectal cancer(CRC)has not been fully elucidated.In previous studies,it was found that S100A8 may regulate EMT.This study aimed to clarify the role of S100A8 in TGF-β-induced EMT and explore the underlying mechanism in CRC.Methods:S100A8 and upstream transcription factor 2(USF2)expression was detected by immunohistochemistry in 412 CRC tissues.Kaplan-Meier survival analysis was performed.In vitro,Western blot,and migration and invasion assays were performed to investigate the effects of S100A8 and USF2 on TGF-β-induced EMT.Mouse metastasis models were used to determine in vivo metastasis ability.Luciferase reporter and chromatin immunoprecipitation assay were used to explore the role of USF2 on S100A8 transcription.Results:During TGF-β-induced EMT in CRC cells,S100A8 and the transcription factor USF2 were upregulated.S100A8 promoted cell migration and invasion and EMT.USF2 transcriptionally regulated S100A8 expression by directly binding to its promoter region.Furthermore,TGF-βenhanced the USF2/S100A8 signaling axis of CRC cells whereas extracellular S100A8 inhibited the USF2/S100A8 axis of CRC cells.S100A8 expression in tumor cells was associated with poor overall survival in CRC.USF2 expression was positively related to S100A8 expression in tumor cells but negatively related to S100A8-positive stromal cells.Conclusions:TGF-βwas found to promote EMT and metastasis through the USF2/S100A8 axis in CRC while extracellular S100A8 suppressed the USF2/S100A8 axis.USF2 was identified as an important switch on the intracellular and extracellular S100A8 feedback loop.展开更多
基金National Key R and D Program of China,No.2016YFC1306700The Key Projects of National Natural Science Foundation of China,No.81830040+1 种基金Science and Technology Program of Guangdong,China,No.2018B030334001Program of Excellent Talents in Medical Science of Jiangsu Province,China,No.JCRCA2016006.
文摘This review summarizes the anti-depressant mechanisms of repetitive transcranial magnetic stimulation in preclinical studies,including anti-inflammatory effects mediated by activation of nuclear factor-E2-related factor 2 signaling pathway,anti-oxidative stress effects,enhancement of synaptic plasticity and neurogenesis via activation of the endocannabinoid system and brain derived neurotrophic factor signaling pathway,increasing the content of monoamine neurotransmitters via inhibition of Sirtuin 1/monoamine oxidase A signaling pathway,and reducing the activity of the hypothalamic-pituitary-adrenocortical axis.We also discuss the shortcomings of transcranial magnetic stimulation in preclinical studies such as inaccurate positioning,shallow depth of stimulation,and difficulty in elucidating the neural circuit mechanism up-and down-stream of the stimulation target brain region.
文摘The purpose of this study was to determine the associations between urinary estradiol (E2) metabolite concentration and medial knee loading with radiographic disease severity in middle aged women with initial stage knee osteoarthritis (OA). Women presenting with knee pain were recruited into a cross-sectional correlation study (KOA, n = 9, age = 52 ± 4 yrs). Self report menstrual history, the Modified Baecke Questionnaire and the Knee Injury and Osteoarthritis Outcome Score (KOOS) subjective data were collected. A fasting blood sample (follicle stimulating hormone (FSH) and Tumor Necrosis Factor-α (TNF-α)), and urine catch (16α-hydroxyestrone and 2-hydroxyestrone) were collected. Gait analysis using an 8-camera motion analysis system assessed internal knee varus moment and foot progression angle. Pearson Product moments tested for associations between urinary 16α-hydroxyestrone and 2-hydroxyestrone, TNF-α, medial knee loading, and radiographic disease severity (Kellgren/Lawrence (K/L) radiographic score). Significant correlations were found within the hormonal biomarkers (r = 0.94, p p p = 0.31). No correlations were found for radiographic disease severity or TNF-α. The lack of association between hormonal and biomechanical variables could be due to large variability of the E2 metabolites seen in the menopause transition and the limited structural changes of initial staged knee OA.
基金This work was supported by the grants of the National Natural Science Foundation of China(81772570)the Open Projects of State Key Laboratory of Molecular Oncology(SKL-KF-2019-17)the Program of Introducing Talents of Discipline to Universities(B13026).
文摘Background:The transforming growth factor-β(TGF-β)pathway plays a pivotal role in inducing epithelial-mesenchymal transition(EMT),which is a key step in cancer invasion and metastasis.However,the regulatory mechanism of TGF-βin inducing EMT in colorectal cancer(CRC)has not been fully elucidated.In previous studies,it was found that S100A8 may regulate EMT.This study aimed to clarify the role of S100A8 in TGF-β-induced EMT and explore the underlying mechanism in CRC.Methods:S100A8 and upstream transcription factor 2(USF2)expression was detected by immunohistochemistry in 412 CRC tissues.Kaplan-Meier survival analysis was performed.In vitro,Western blot,and migration and invasion assays were performed to investigate the effects of S100A8 and USF2 on TGF-β-induced EMT.Mouse metastasis models were used to determine in vivo metastasis ability.Luciferase reporter and chromatin immunoprecipitation assay were used to explore the role of USF2 on S100A8 transcription.Results:During TGF-β-induced EMT in CRC cells,S100A8 and the transcription factor USF2 were upregulated.S100A8 promoted cell migration and invasion and EMT.USF2 transcriptionally regulated S100A8 expression by directly binding to its promoter region.Furthermore,TGF-βenhanced the USF2/S100A8 signaling axis of CRC cells whereas extracellular S100A8 inhibited the USF2/S100A8 axis of CRC cells.S100A8 expression in tumor cells was associated with poor overall survival in CRC.USF2 expression was positively related to S100A8 expression in tumor cells but negatively related to S100A8-positive stromal cells.Conclusions:TGF-βwas found to promote EMT and metastasis through the USF2/S100A8 axis in CRC while extracellular S100A8 suppressed the USF2/S100A8 axis.USF2 was identified as an important switch on the intracellular and extracellular S100A8 feedback loop.
