NR4A2 is a transcription factor belonging to the steroid orphan nuclear receptor superfamily.It was originally considered to be essential in the generation and maintenance of dopaminergic neurons,and associated with n...NR4A2 is a transcription factor belonging to the steroid orphan nuclear receptor superfamily.It was originally considered to be essential in the generation and maintenance of dopaminergic neurons,and associated with neurological disorders such as Parkinson's disease.Recently,NR4A2 has been found to play a critical role in some inflammatory diseases and cancer.NR4A2 can be efficiently trans-activated by some proinflammatory cytokines,such as tumor necrosis factor-α,interleukin-1β,and vascular endothelial growth factor(VEGF).The nuclear factor-κB signaling pathway serves as a principal regulator of inducible NR4A expression in immune cells.NR4A2 can trans-activate Foxp3,a hallmark specifically expressed in regulatory T(Treg) cells,and plays a critical role in the differentiation,maintenance,and function of Treg cells.NR4A2 in T lymphocytes is pivotal for Treg cell induction and suppression of aberrant induction of Th1 under physiological and pathological conditions.High density of Foxp3 + Treg cells is significantly associated with gastrointestinal inflammation,tumor immune escape,and disease progression.NR4A2 is produced at high levels in CD133 + colorectal carcinoma(CRC) cells and significantly upregulated by cyclooxygenase-2-derived prostaglandin E 2 in a cyclic adenosine monophosphate(cAMP)/protein kinase A(PKA)-dependent manner in CRC cells.The cAMP/PKA signaling pathway is the common pathway of NR4A2-related inflammation and cancer.NR4A2 trans-activates osteopontin,a direct target of the Wnt/β-catenin pathway associated with CRC invasion,metastasis,and poor prognosis.Knockdown of endogenous NR4A2 expression attenuates VEGF-induced endothelial cell proliferation,migration and in vivo angiogenesis.Taken together,NR4A2 emerges as an important nuclear factor linking gastrointestinal inflammation and cancer,especially CRC,and should serve as a candidate therapeutic target for inflammation-related gastrointestinal cancer.展开更多
Integrative Body-Mind Training(IBMT) originates from ancient Eastern tradition.The method stresses no effort to control thoughts,but instead a state of restful alertness that allows a high degree of awareness of the...Integrative Body-Mind Training(IBMT) originates from ancient Eastern tradition.The method stresses no effort to control thoughts,but instead a state of restful alertness that allows a high degree of awareness of the body,breathing,and external instructions.A series of studies indicates that IBMT improves attention and self-regulation through interaction between the central(brain) and the autonomic(body) nervous systems.The present review mainly summarizes the recent results of IBMT studies and proposes how it changes the state of brain and body to lead to positive outcomes.Future directions in this field are also discussed.展开更多
Tinnitus is defined as a perception of sound without any external sound source.Chronic tinnitus is a frequent condition that can affect the quality of life.So far,no causal cure for tinnitus has been documented,and mo...Tinnitus is defined as a perception of sound without any external sound source.Chronic tinnitus is a frequent condition that can affect the quality of life.So far,no causal cure for tinnitus has been documented,and most pharmacologic and psychosomatic treatment modalities aim to diminish tinnitus’impact on the quality of life.Neuromodulation,a novel therapeutic modality,which aims at alternating nerve activity through a targeted delivery of a stimulus,has emerged as a potential option in tinnitus treatment.This review provides a brief overview of the current neuromodulation techniques as tinnitus treatment options.The main intention is to provide updated knowledge especially for medical professionals counselling tinnitus patients in this emerging field of medicine.Non-invasive methods such as repetitive transcranial magnetic stimulation,transcranial electrical stimulation,neurofeedback,and transcutaneous vagus nerve stimulation were included,as well as invasive methods such as implanted vagus nerve stimulation and invasive brain stimulation.Some of these neuromodulation techniques revealed promising results;nevertheless,further research is needed,especially regarding the pathophysiological principle as to how these neuromodulation techniques work and what neuronal change they induce.Various studies suggest that individually different brain states and networks are involved in the generation and perception of tinnitus.Therefore,in the future,individually tailored neuromodulation strategies could be a promising approach in tinnitus treatment for achieving a more substantial and longer lasting improvement of complaints.展开更多
Objective: To observe therapeutic effect of acupuncture for regulating the liver on depressive neurosis. Methods: In a multi-center randomized controlled trial, 440 patients were divided into 3 groups: Acupuncture gro...Objective: To observe therapeutic effect of acupuncture for regulating the liver on depressive neurosis. Methods: In a multi-center randomized controlled trial, 440 patients were divided into 3 groups: Acupuncture group for regulating the liver (Acup., 176 cases) was treated by acupuncture at Siguan Points, i.e. bilateral Hegu (LI 4) and Taichong (LR 3), Baihui (GV 20) and Yintang (EX-HN3) plus ear-acupuncture, Prozac group (P., 176 cases) by oral administration of Prozac, and Non-acupoint needling group (NAN, 88 cases) by acupuncture at non-acupoints as acupuncture placebo. Self-rating Depression Scale (SDS) was examined before treatment, and one month, two and three months after treatment respectively to evaluate therapeutic effect, and Rating Scale for Side Effects (SERS) was used to evaluate the safety. Results: After one month of treatment, SDS scores in Acup. Group were significantly lower than that in P. Group (P<0.05) and than that in NAN Group (P<0.01), and SDS scores in P. Group were lower than that in NAN Group (P<0.05), showing the SDS scores in Acup. Group <P. Group <NAN Group. After 2 months of treatment, SDS scores in Acup. Group were also significantly lower than that in P. Group (P<0.01) and than that in NAN Group (P<0.01), and SDS scores in P. Group were also lower than that in NAN Group (P<0.05), showing the SDS scores in Acup. Group <P. Group <NAN Group. After 3 months of treatment, SDS scores in Acup. Group were also significantly lower than that in P. Group (P<0.01) and than that in NAN Group (P<0.01), and SDS scores in P. Group were also lower than that in NAN Group (P<0.01), showing the SDS score in Acup. Group <P. Group <NAN Group. After treatment, SERS scores were 0.16±0.95, 6.51±5.09 and 0.23±1.36 in Acup. Group, P. Group and NAN Group respectively. A significant difference existed between Acup. Group and P. Group (P<0.05), but no significant difference between Acup. Group and NAN Group (P>0.05), showing the SERS scores in Acup. Group <NAN Group <P. Group. No side effect was found in Acup. and NAN groups. Conclusion: The therapeutic effect of acupuncture on depressive neurosis is better than or similar to that of Prozac but with less side effect.展开更多
The suprachiasmatic nucleus(SCN)is the master circadian pacemaker that drives body temperature rhythm.Time-restricted feeding(TRF)has potential as a preventative or therapeutic approach against many diseases.The poten...The suprachiasmatic nucleus(SCN)is the master circadian pacemaker that drives body temperature rhythm.Time-restricted feeding(TRF)has potential as a preventative or therapeutic approach against many diseases.The potential side effects of TRF remain unknown.Here we show that daily 4-h TRF treatment in mice can severely impair body temperature homeostasis and can result in lethality.Nearly half of the mice died at 21℃,and all mice died at 18℃during 4-h TRF.This effect was modulated by the circadian clock and was associated with severe hypothermia due to loss of body temperature homeostasis.Remarkably,disrupting the circadian clock by SCN lesions or constant light rescued lethality during TRF.Analysis of circadian gene expression in the dorsomedial hypothalamus(DMH)demonstrated that TRF reprograms rhythmic transcriptome in DMH and suppresses expression of genes,such as Ccr5 and Calcrl,which are involved in thermoregulation.Together,our results demonstrated a potent effect of TRF on body temperature homeostasis and the role of SCN function in this process.Our results further suggested that circadian arrhythmicity can have potential beneficial effects under certain stress conditions.展开更多
基金Supported by National Natural Science Foundation of China, No.81025015,30921006,91129301
文摘NR4A2 is a transcription factor belonging to the steroid orphan nuclear receptor superfamily.It was originally considered to be essential in the generation and maintenance of dopaminergic neurons,and associated with neurological disorders such as Parkinson's disease.Recently,NR4A2 has been found to play a critical role in some inflammatory diseases and cancer.NR4A2 can be efficiently trans-activated by some proinflammatory cytokines,such as tumor necrosis factor-α,interleukin-1β,and vascular endothelial growth factor(VEGF).The nuclear factor-κB signaling pathway serves as a principal regulator of inducible NR4A expression in immune cells.NR4A2 can trans-activate Foxp3,a hallmark specifically expressed in regulatory T(Treg) cells,and plays a critical role in the differentiation,maintenance,and function of Treg cells.NR4A2 in T lymphocytes is pivotal for Treg cell induction and suppression of aberrant induction of Th1 under physiological and pathological conditions.High density of Foxp3 + Treg cells is significantly associated with gastrointestinal inflammation,tumor immune escape,and disease progression.NR4A2 is produced at high levels in CD133 + colorectal carcinoma(CRC) cells and significantly upregulated by cyclooxygenase-2-derived prostaglandin E 2 in a cyclic adenosine monophosphate(cAMP)/protein kinase A(PKA)-dependent manner in CRC cells.The cAMP/PKA signaling pathway is the common pathway of NR4A2-related inflammation and cancer.NR4A2 trans-activates osteopontin,a direct target of the Wnt/β-catenin pathway associated with CRC invasion,metastasis,and poor prognosis.Knockdown of endogenous NR4A2 expression attenuates VEGF-induced endothelial cell proliferation,migration and in vivo angiogenesis.Taken together,NR4A2 emerges as an important nuclear factor linking gastrointestinal inflammation and cancer,especially CRC,and should serve as a candidate therapeutic target for inflammation-related gastrointestinal cancer.
基金supported by the National Natural Science Foundation of China (60971096)National Basic Research Development Program of China (973 Program,2012CB518200)
文摘Integrative Body-Mind Training(IBMT) originates from ancient Eastern tradition.The method stresses no effort to control thoughts,but instead a state of restful alertness that allows a high degree of awareness of the body,breathing,and external instructions.A series of studies indicates that IBMT improves attention and self-regulation through interaction between the central(brain) and the autonomic(body) nervous systems.The present review mainly summarizes the recent results of IBMT studies and proposes how it changes the state of brain and body to lead to positive outcomes.Future directions in this field are also discussed.
文摘Tinnitus is defined as a perception of sound without any external sound source.Chronic tinnitus is a frequent condition that can affect the quality of life.So far,no causal cure for tinnitus has been documented,and most pharmacologic and psychosomatic treatment modalities aim to diminish tinnitus’impact on the quality of life.Neuromodulation,a novel therapeutic modality,which aims at alternating nerve activity through a targeted delivery of a stimulus,has emerged as a potential option in tinnitus treatment.This review provides a brief overview of the current neuromodulation techniques as tinnitus treatment options.The main intention is to provide updated knowledge especially for medical professionals counselling tinnitus patients in this emerging field of medicine.Non-invasive methods such as repetitive transcranial magnetic stimulation,transcranial electrical stimulation,neurofeedback,and transcutaneous vagus nerve stimulation were included,as well as invasive methods such as implanted vagus nerve stimulation and invasive brain stimulation.Some of these neuromodulation techniques revealed promising results;nevertheless,further research is needed,especially regarding the pathophysiological principle as to how these neuromodulation techniques work and what neuronal change they induce.Various studies suggest that individually different brain states and networks are involved in the generation and perception of tinnitus.Therefore,in the future,individually tailored neuromodulation strategies could be a promising approach in tinnitus treatment for achieving a more substantial and longer lasting improvement of complaints.
文摘Objective: To observe therapeutic effect of acupuncture for regulating the liver on depressive neurosis. Methods: In a multi-center randomized controlled trial, 440 patients were divided into 3 groups: Acupuncture group for regulating the liver (Acup., 176 cases) was treated by acupuncture at Siguan Points, i.e. bilateral Hegu (LI 4) and Taichong (LR 3), Baihui (GV 20) and Yintang (EX-HN3) plus ear-acupuncture, Prozac group (P., 176 cases) by oral administration of Prozac, and Non-acupoint needling group (NAN, 88 cases) by acupuncture at non-acupoints as acupuncture placebo. Self-rating Depression Scale (SDS) was examined before treatment, and one month, two and three months after treatment respectively to evaluate therapeutic effect, and Rating Scale for Side Effects (SERS) was used to evaluate the safety. Results: After one month of treatment, SDS scores in Acup. Group were significantly lower than that in P. Group (P<0.05) and than that in NAN Group (P<0.01), and SDS scores in P. Group were lower than that in NAN Group (P<0.05), showing the SDS scores in Acup. Group <P. Group <NAN Group. After 2 months of treatment, SDS scores in Acup. Group were also significantly lower than that in P. Group (P<0.01) and than that in NAN Group (P<0.01), and SDS scores in P. Group were also lower than that in NAN Group (P<0.05), showing the SDS scores in Acup. Group <P. Group <NAN Group. After 3 months of treatment, SDS scores in Acup. Group were also significantly lower than that in P. Group (P<0.01) and than that in NAN Group (P<0.01), and SDS scores in P. Group were also lower than that in NAN Group (P<0.01), showing the SDS score in Acup. Group <P. Group <NAN Group. After treatment, SERS scores were 0.16±0.95, 6.51±5.09 and 0.23±1.36 in Acup. Group, P. Group and NAN Group respectively. A significant difference existed between Acup. Group and P. Group (P<0.05), but no significant difference between Acup. Group and NAN Group (P>0.05), showing the SERS scores in Acup. Group <NAN Group <P. Group. No side effect was found in Acup. and NAN groups. Conclusion: The therapeutic effect of acupuncture on depressive neurosis is better than or similar to that of Prozac but with less side effect.
基金supported by the National Natural Science Foundation of China(31630091,3123004931600958)Royal SocietyNewton Advance Fellowship(NA150373)+5 种基金Ministry of Science and Technology(YFA0801100)to YXNational Institutes of Health(1R35GM118118)Cancer Prevention and Research Institute of Texas(RP160268)Welch Foundation(I-1560)to YLPriority Academic Program Development of the Jiangsu Higher Education Institutes(PAPD)National Center for International Research(2017B01012)。
文摘The suprachiasmatic nucleus(SCN)is the master circadian pacemaker that drives body temperature rhythm.Time-restricted feeding(TRF)has potential as a preventative or therapeutic approach against many diseases.The potential side effects of TRF remain unknown.Here we show that daily 4-h TRF treatment in mice can severely impair body temperature homeostasis and can result in lethality.Nearly half of the mice died at 21℃,and all mice died at 18℃during 4-h TRF.This effect was modulated by the circadian clock and was associated with severe hypothermia due to loss of body temperature homeostasis.Remarkably,disrupting the circadian clock by SCN lesions or constant light rescued lethality during TRF.Analysis of circadian gene expression in the dorsomedial hypothalamus(DMH)demonstrated that TRF reprograms rhythmic transcriptome in DMH and suppresses expression of genes,such as Ccr5 and Calcrl,which are involved in thermoregulation.Together,our results demonstrated a potent effect of TRF on body temperature homeostasis and the role of SCN function in this process.Our results further suggested that circadian arrhythmicity can have potential beneficial effects under certain stress conditions.