Functional dyspepsia (FD) is a common functional gastrointestinal disease which bears a significant burden on society and individuals. Despite the high prevalence of FD, its pathophysiology remains poorly understood and the treatment options are limited and unsatisfactory. In the absence of effective pharmacological treatments for FD, non-pharmacological approaches, including: reassurance, lifestyle modification, psychotherapy, dietary interventions, medical food, acupuncture, and electrical stimulation and modulation are sought after by many physicians and FD patients. In this article, we review clinical studies which investigate nonpharmacological therapies for FD. We will also discuss potential mechanisms involved in the therapeutic effects of these nonpharmacological approaches. Though the evidences to support the routine use of the non-pharmacological management is still lacking, the non-invasive nature and potentially minimal side-effects of these therapies may be attractive in the FD management. In order to confirm the clinical effectiveness of these non-pharmacological approaches, more well-conducted, methodologically rigorous, and large-scaled clinical trials are required.

Objective: Danshensu, a phenylpropanoid compound, is derived from the dry root and rhizome of Danshen (Salvia miltiorrhiza), a traditional Chinese medicinal herb. Evidence suggests that danshensu protects isolated rat hearts against ischemia/reperfusion injury by activating the protein kinase B (Akt)/extracellular signal-regulated kinase (ERK) pathway or by inhibiting autophagy and apoptosis through the activation of mammalian target of rapamycin (mTOR) signaling. Furthermore, danshensu promotes the postischemic regeneration of brain cells by upregulating the expression of brain-derived neurotrophic factor (BDNF) in the peri-infarct region. However, basic and clinical studies are needed to investigate the antidepressant effects danshensu and determine whether brain mTOR signaling and BDNF activation mediate these effects. The aforementioned need prompted us to conduct the present study. Methods: Using a C57BL/6 mouse model, we investigated the antidepressant-like effects of danshensu and the mechanisms that mediate these effects. To elucidate the mechanisms, we analyzed the roles of Akt/ERK–mTOR signaling and BDNF activation in mediating the antidepressant-like effects of danshensu. Results: Danshensu exerted its antidepressant-like effects by activating the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) of Akt/ERK–mTOR signaling and promoting BDNF release. Treatment with danshensu increased the level of glutamate receptor 1 phosphorylation at the protein kinase A site. Conclusion Our study may be the first to demonstrate that the antidepressant effects of danshensu are dependent on the activation of the AMPAR–mTOR signaling pathway, are correlated with the elevation of BDNF level, and facilitate the insertion of AMPAR into the postsynaptic membrane. This study also pioneers in unveiling the potential of danshensu against depressive disorders.

Objective: Danshensu, a phenylpropanoid compound, is derived from the dry root and rhizome of Danshen (Salvia miltiorrhiza), a traditional Chinese medicinal herb. Evidence suggests that danshensu protects isolated rat hearts against ischemia/reperfusion injury by activating the protein kinase B (Akt)/extracellular signal-regulated kinase (ERK) pathway or by inhibiting autophagy and apoptosis through the activation of mammalian target of rapamycin (mTOR) signaling. Furthermore, danshensu promotes the postischemic regeneration of brain cells by upregulating the expression of brain-derived neurotrophic factor (BDNF) in the peri-infarct region. However, basic and clinical studies are needed to investigate the antidepressant effects danshensu and determine whether brain mTOR signaling and BDNF activation mediate these effects. The aforementioned need prompted us to conduct the present study. Methods: Using a C57BL/6 mouse model, we investigated the antidepressant-like effects of danshensu and the mechanisms that mediate these effects. To elucidate the mechanisms, we analyzed the roles of Akt/ERK–mTOR signaling and BDNF activation in mediating the antidepressant-like effects of danshensu. Results: Danshensu exerted its antidepressant-like effects by activating the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) of Akt/ERK–mTOR signaling and promoting BDNF release. Treatment with danshensu increased the level of glutamate receptor 1 phosphorylation at the protein kinase A site. Conclusion Our study may be the first to demonstrate that the antidepressant effects of danshensu are dependent on the activation of the AMPAR–mTOR signaling pathway, are correlated with the elevation of BDNF level, and facilitate the insertion of AMPAR into the postsynaptic membrane. This study also pioneers in unveiling the potential of danshensu against depressive disorders.

Objective: Danshensu, a phenylpropanoid compound, is derived from the dry root and rhizome of Danshen (Salvia miltiorrhiza), a traditional Chinese medicinal herb. Evidence suggests that danshensu protects isolated rat hearts against ischemia/reperfusion injury by activating the protein kinase B (Akt)/extracellular signal-regulated kinase (ERK) pathway or by inhibiting autophagy and apoptosis through the activation of mammalian target of rapamycin (mTOR) signaling. Furthermore, danshensu promotes the postischemic regeneration of brain cells by upregulating the expression of brain-derived neurotrophic factor (BDNF) in the peri-infarct region. However, basic and clinical studies are needed to investigate the antidepressant effects danshensu and determine whether brain mTOR signaling and BDNF activation mediate these effects. The aforementioned need prompted us to conduct the present study. Methods: Using a C57BL/6 mouse model, we investigated the antidepressant-like effects of danshensu and the mechanisms that mediate these effects. To elucidate the mechanisms, we analyzed the roles of Akt/ERK–mTOR signaling and BDNF activation in mediating the antidepressant-like effects of danshensu. Results: Danshensu exerted its antidepressant-like effects by activating the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) of Akt/ERK–mTOR signaling and promoting BDNF release. Treatment with danshensu increased the level of glutamate receptor 1 phosphorylation at the protein kinase A site. Conclusion Our study may be the first to demonstrate that the antidepressant effects of danshensu are dependent on the activation of the AMPAR–mTOR signaling pathway, are correlated with the elevation of BDNF level, and facilitate the insertion of AMPAR into the postsynaptic membrane. This study also pioneers in unveiling the potential of danshensu against depressive disorders.

Objective: Danshensu, a phenylpropanoid compound, is derived from the dry root and rhizome of Danshen (Salvia miltiorrhiza), a traditional Chinese medicinal herb. Evidence suggests that danshensu protects isolated rat hearts against ischemia/reperfusion injury by activating the protein kinase B (Akt)/extracellular signal-regulated kinase (ERK) pathway or by inhibiting autophagy and apoptosis through the activation of mammalian target of rapamycin (mTOR) signaling. Furthermore, danshensu promotes the postischemic regeneration of brain cells by upregulating the expression of brain-derived neurotrophic factor (BDNF) in the peri-infarct region. However, basic and clinical studies are needed to investigate the antidepressant effects danshensu and determine whether brain mTOR signaling and BDNF activation mediate these effects. The aforementioned need prompted us to conduct the present study. Methods: Using a C57BL/6 mouse model, we investigated the antidepressant-like effects of danshensu and the mechanisms that mediate these effects. To elucidate the mechanisms, we analyzed the roles of Akt/ERK–mTOR signaling and BDNF activation in mediating the antidepressant-like effects of danshensu. Results: Danshensu exerted its antidepressant-like effects by activating the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) of Akt/ERK–mTOR signaling and promoting BDNF release. Treatment with danshensu increased the level of glutamate receptor 1 phosphorylation at the protein kinase A site. Conclusion Our study may be the first to demonstrate that the antidepressant effects of danshensu are dependent on the activation of the AMPAR–mTOR signaling pathway, are correlated with the elevation of BDNF level, and facilitate the insertion of AMPAR into the postsynaptic membrane. This study also pioneers in unveiling the potential of danshensu against depressive disorders.

Objective: Danshensu, a phenylpropanoid compound, is derived from the dry root and rhizome of Danshen (Salvia miltiorrhiza), a traditional Chinese medicinal herb. Evidence suggests that danshensu protects isolated rat hearts against ischemia/reperfusion injury by activating the protein kinase B (Akt)/extracellular signal-regulated kinase (ERK) pathway or by inhibiting autophagy and apoptosis through the activation of mammalian target of rapamycin (mTOR) signaling. Furthermore, danshensu promotes the postischemic regeneration of brain cells by upregulating the expression of brain-derived neurotrophic factor (BDNF) in the peri-infarct region. However, basic and clinical studies are needed to investigate the antidepressant effects danshensu and determine whether brain mTOR signaling and BDNF activation mediate these effects. The aforementioned need prompted us to conduct the present study. Methods: Using a C57BL/6 mouse model, we investigated the antidepressant-like effects of danshensu and the mechanisms that mediate these effects. To elucidate the mechanisms, we analyzed the roles of Akt/ERK–mTOR signaling and BDNF activation in mediating the antidepressant-like effects of danshensu. Results: Danshensu exerted its antidepressant-like effects by activating the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) of Akt/ERK–mTOR signaling and promoting BDNF release. Treatment with danshensu increased the level of glutamate receptor 1 phosphorylation at the protein kinase A site. Conclusion Our study may be the first to demonstrate that the antidepressant effects of danshensu are dependent on the activation of the AMPAR–mTOR signaling pathway, are correlated with the elevation of BDNF level, and facilitate the insertion of AMPAR into the postsynaptic membrane. This study also pioneers in unveiling the potential of danshensu against depressive disorders.

A growing body of evidence has demonstrated an intricate association between inflammatory bowel disease (IBD) and neurodegenerative conditions, expanding beyond previous foci of comorbidities between IBD and mood disorders. These new discoveries stem from an improved understanding of the gut-microbiome-brain axis: specifically, the ability of the intestinal microbiota to modulate inflammation and regulate neuromodulatory compounds. Clinical retrospective studies incorporating large sample sizes and population-based cohorts have demonstrated and confirmed the relevance of IBD and chronic neurodegeneration in clinical medicine. In this review, we expound upon the current knowledge on the gut-microbiome-brain axis, highlighting several plausible mechanisms linking IBD with neurodegeneration. We also summarize the known associations between IBD with Parkinson disease, Alzheimer disease, vascular dementia and ischemic stroke, and multiple sclerosis in a clinical context. Finally, we discuss the implications of an improved understanding of the gut-microbiome-brain axis in preventing, diagnosing, and managing neurodegeneration among IBD and non-IBD patients.

BACKGROUND/AIMS: Both sexual and physical abuse history have been reported to be associated with irritable bowel syndrome (IBS) in Western countries. The impact of abuse history in IBS patients in Asia remains unclear. We aim to determine the prevalence of abuse history, its associated psychological profiles, and sleep problems among IBS patients in Taiwan. METHODS: In total, 194 Rome III-defined IBS patients were invited to participate. Age- and sex-matched healthy carriers of chronic hepatitis B or hepatitis C without chronic abdominal symptoms were identified as disease-controls. We administered a validated questionnaire to evaluate bowel symptoms, physical/sexual abuse history, anxiety/depression (Hospital Anxiety and Depression Scale [HADS]), and sleep quality. RESULTS: IBS patients had a significantly higher prevalence of sexual abuse history than the disease-control group both before (16.5% vs 6.7%, P < 0.05) and after (16.0% vs 6.6%, P < 0.05) adolescence. These significant differences were mainly observed in women (13.4% vs 3.4%, P < 0.05). No difference was noted in history of physical abuse between the 2 groups. IBS patients with a history of sexual abuse had significantly higher HADS scores and higher frequencies of sleep difficulty than those without. CONCLUSIONS: In Taiwan, sexual abuse history was more prevalent in female IBS patients than controls. Sexual abuse history may contribute to higher anxiety/depression levels and sleep difficulties, which are commonly experienced in IBS patients. In Asia, abuse history should be obtained when approaching IBS patients to facilitate better management.
Adolescent ; Anxiety ; Asia ; Depression ; Female ; Hepatitis B, Chronic ; Hepatitis C ; Humans ; Irritable Bowel Syndrome ; Physical Abuse ; Prevalence ; Sex Offenses ; Taiwan

Objective: Valproic acid (VPA) is an anticonvulsant and commonly long term used as a mood stabilizer for patients with mood disorders. However its chronic effects on the hematological changes were noticed and need to be further evaluated. In this study, we evaluated, in Taiwanese Han Chinese patients with bipolar disorders (BD), the chronic effects of VPA or VPA plus dextromethorphan (DM) on the hematological molecules (white blood cell [WBCs], red blood cells [RBCs], hemoglobin, hematocrit, and platelets). Methods: In a 12-week, randomized, double-blind study, we randomly assigned BD patients to one of three groups: VPA plus either placebo (VPA＋P, n = 57) or DM (30 mg/day, VPA＋DM30, n = 56) or 60 mg/day (VPA＋DM60, n = 53). The Young Mania Rating Scale and Hamilton Depression Rating Scale were used to evaluate symptom severity, and the hematological molecules were checked. Results: Paired t test showed that the WBC, neutrophils, platelets and RBCs were significantly lowered after 12 weeks of VPA＋P or VPA＋DM30 treatment. VPA＋DM60 represented the protective effects in the WBCs, neutrophils, and RBCs but not in the platelets. We further calculated the changes of each hematological molecules after 12 weeks treatment. We found that combination use of DM60 significantly improved the decline in neutrophils induced by the long-term VPA treatment. Conclusion Hematological molecule levels were lower after long-term treatment with VPA. VPA＋DM60, which yielded the protective effect in hematological change, especially in the neutrophil counts. Thus, DM might be adjunct therapy for maintaining hematological molecules in VPA treatment.

Objective: The relationship between adverse childhood experiences and methamphetamine use disorder (MUD) has been shown in previous studies; nevertheless, the underlying neural mechanisms remain elusive. Childhood trauma is associated with aberrant functional connectivity (FC) within the default-mode network (DMN). Furthermore, within the DMN, FC may contribute to impaired self-awareness in addiction, while cross-network FC is critical for relapse.We aimed to investigate whether childhood trauma was associated with DMN-related resting-state FC among healthy controls and patients with MUD and to examine whether DMN-related FC affected the effect of childhood trauma on the symptom load of MUD diagnosis. Methods: Twenty-seven male patients with MUD and 27 male healthy controls were enrolled and completed the Childhood Trauma Questionnaire. DMN-related resting-state FC was examined using functional magnetic resonance imaging. Results: There were 47.1% healthy controls and 66.7% MUD patients in this study with adverse childhood experiences.Negative correlations between adverse childhood experiences and within-DMN FC were observed in both healthy controls and MUD patients, while within-DMN FC was significantly altered in MUD patients. The detrimental effects of adverse childhood experiences on MUD patients may be attenuated through DMN-executive control networks (ECN) FC. Conclusion Adverse childhood experiences were negatively associated with within-DMN FC in MUD patients and healthy controls. However, DMN-ECN FC may attenuate the effects of childhood trauma on symptoms load of MUD.