Gestational Vitamin E Status and Gestational Diabetes Mellitus: A Retrospective Cohort Study.

OBJECTIVES: To examine the association between vitamin E (VE) status and gestational diabetes mellitus (GDM). METHODS: A retrospective cohort study was conducted by using data of 52,791 women at 137 hospitals across 22 provinces of China. A fasting plasma glucose (FPG) level of ≥5.1 mmol/L between the 24th and 40th weeks of gestation was used as the criteria for the diagnosis of GDM. Mean FPG level and GDM rate were calculated within each combination of the first-trimester VE concentration categories and gestational change categories. The associations of the first-trimester VE concentrations and gestational VE change with FPG and GDM were examined by employing generalized additive models (GAMs). RESULTS: 7162 (13.57%) cases were diagnosed with GDM. The GDM rate was 22.44%, 11.50%, 13.41%, 12.87%, 13.17%, 13.44%, 12.64%, and 14.24% among women with the first-trimester VE concentrations of <7.2, 7.2-7.9, 8.0-9.3, 9.4-11.0, 11.1-13.2, 13.3-15.8, 15.9-17.7, and 17.8-35.9 mg/L, respectively. The GDM rate was 15.96%, 13.10%, 13.64%, and 12.87% among women with gestational VE change of <0, 0-0.19, 0.20-0.29, ≥0.30 mg/L per week, respectively. Multivariable adjusted GAM analyses found that the first-trimester VE concentration was associated with the FPG levels and GDM risk in an L-shaped pattern; the FPG levels and GDM risk decreased sharply to a threshold (around 7 mg/L), and then were keep flat. Gestational VE decreases when the first-trimester VE level was less than 11 mg/L were related to increased FPG levels and GDM risk. CONCLUSIONS: Both low first-trimester VE levels and subsequent gestational VE decrease were related with increased risk of GDM. The findings suggest the necessity of having VE-rich foods and appropriate VE supplementation to prevent GDM for pregnant women with low baseline VE levels.

The role and mechanism of tryptophan - kynurenine metabolic pathway in depression.

Major depressive disorder (MDD) is a common mental illness characterized by persistent low mood and anhedonia, normally accompanied with cognitive impairment. Due to its rising incidence and high rate of recurrence and disability, MDD poses a substantial threat to patients' physical and mental health, as well as a significant economic cost to society. However, the etiology and pathogenesis of MDD are still unclear. Chronic inflammation may cause indoleamine-2,3-dioxygenase (IDO) to become overactive throughout the body and brain, resulting in excess quinolinic acid (QUIN) and less kynuric acid (KYNA) in the brain. QUIN's neurotoxicity damages glial cells and neurons, accelerates neuronal apoptosis, hinders neuroplasticity, and causes depression due to inflammation. Therefore, abnormal TRP-KYN metabolic pathway and its metabolites have been closely related to MDD, suggesting changes in the TRP-KYN metabolic pathway might contribute to MDD. In addition, targeting TRP-KYN with traditional Chinese medicine showed promising treatment effects for MDD. This review summarizes the recent studies on the TRP-KYN metabolic pathway and its metabolites in depression, which would provide a theoretical basis for exploring the etiology and pathogenesis of depression.

Association of Gestational Vitamin E Status With Pre-eclampsia: A Retrospective, Multicenter Cohort Study.

Introduction: Pre-eclampsia is the second leading cause of maternal mortality worldwide. The controversy for the association of vitamin E with pre-eclampsia has raged unabated for two decades. We aimed to determine the association of vitamin E level in the first trimester and the gestational change with pre-eclampsia. Materials and Methods: A retrospective cohort study was conducted among singleton pregnant women aged 15-49 years at 137 hospitals in China. Serum vitamin E concentrations in the first trimester and at pre-eclampsia assessment time were uniformly quantified in a laboratory by high performance liquid chromatography. Logistic regression models with restricted cubic splines were performed to reveal a non-linear association of vitamin E concentrations in the first trimester and the gestational change with pre-eclampsia. Results: We included 73 317 participants (47.8% aged 25-29 years) and 2.28% were diagnosed with pre-eclampsia. Higher risk was observed in those with lower concentration in the first trimester and greater gestational decrease, with a range from 0.81 to 80.60%. A non-linear L-shaped association was observed between vitamin E concentrations in the first trimester and pre-eclampsia, suggesting a threshold at 7.3 mg/L and a ceiling effect: the risk saw a steep rise when the concentrations in the first trimester were < 7.3 mg/L but was relatively flat beyond the inflection point. Sharply increased pre-eclampsia risk was also found in those with gestational vitamin E decrease after accounting for the baseline status in the first trimester. However, gestational vitamin E increase was associated with decreased pre-eclampsia risk when the baseline concentrations were < 7.3 mg/L but did not confer additional benefits when it was above the threshold. Conclusion: We demonstrated alarmingly high pre-eclampsia risk in women with vitamin E concentrations of < 7.3 mg/L in the first trimester and gestational vitamin E decrease. These findings underscore the need to supplement vitamin E among pregnant women with low baseline status.

Effects of auricular acupressure on depression in stroke patients: A single-blind randomized controlled trial.

BACKGROUND AND PURPOSE: Post-stroke depression (PSD) has an important impact on rehabilitation, motor recovery, daily activities, social and interpersonal life, and mortality. This study aimed to evaluate the effects of auricular acupressure (AurPrs) on depression in PSD patients. MATERIALS AND METHODS: Fifty-six PSD patients were recruited and randomly assigned to the AurPrs group (receiving AurPrs treatment) or the sham group (receiving sham AurPrs treatment). The outcome was measured by the 17-item Hamilton Rating Scale for Depression (HAMD-17), Zung Self-Rating Depression Scale (SDS), and World Health Organization Quality of Life Brief Version (WHOQOL-BREF). RESULTS: There was a statistically significant difference in HAMD-17 score, SDS score and WHOQOL-BREF score between both groups before and after treatment (P < 0.01). The improvement of the AurPrs group was more obvious than that of the sham group (P < 0.05). CONCLUSION: AurPrs could help to reduce depression levels and improve the quality of life in patients with PSD.

Tetrahydrocurcumin mitigates acute hypobaric hypoxia-induced cerebral oedema and inflammation through the NF-κB/VEGF/MMP-9 pathway.

High-altitude cerebral oedema (HACE) is a potentially fatal manifestation of high-altitude sickness and is caused partly by inflammation and the blood-brain barrier disruption. Tetrahydrocurcumin (THC) has been reported to exert effective antioxidative and anti-inflammatory effects; This study sought to elucidate the underlying mechanism of THC in mitigating HACE using a mouse model. Our results revealed that prophylactic administration of THC (40 mg/kg) for 3 days significantly alleviated the increase in brain water content (BWC), interleukin-1ß (IL-1ß) and TNF-α levels caused by acute hypobaric hypoxia (AHH). Additionally, superoxide dismutase (SOD) activity was increased by THC to enhance the ability to resist hypoxia. Histological and ultrastructural analysis of the cerebrum revealed that THC administration mitigated AHH-induced pericellular oedema and reduced the perivascular space, resulting in the simultaneous remission of oedema and protection of mitochondria in the cerebrum. In vitro, astrocytes exposed to hypoxia (4% O2 ) for 24 hr exhibited and increase in IL-1ß expression followed by an increase in vascular endothelial growth factor (VEGF) levels. Furthermore, THC administration remarkably downregulated VEGF, matrix metallopeptidase-9 (MMP-9), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) expression, both in vivo and in vitro. Our data highlight the potential prophylactic activity of THC in HACE, it effectively mitigates AHH-induced cerebral oedema and inflammation is associated with the inhibition of the NF-κB/ VEGF/MMP-9 pathways.

The Role of Group II Metabotropic Glutamate Receptors in the Striatum in Electroacupuncture Treatment of Parkinsonian Rats.

AIMS: Glutamatergic transmission may play a critical role in the pathogenesis of Parkinson's disease (PD). Electroacupuncture (EA) has been demonstrated to effectively alleviate PD symptoms. In this study, a potential glutamate-dependent mechanism underlying the therapeutic action of EA was investigated. METHODS: The effects of EA stimulation on motor behaviors, dopamine contents, glutamate release, and group II metabotropic glutamate receptor (mGluR2/3) expression in unilateral 6-hydroxydopamine (6-OHDA)-lesioned rats were examined. RESULTS: Unilateral 6-OHDA lesions of the nigrostriatal system caused a marked increase in glutamate content in the ipsilateral cortex and striatum. mGluR2/3 protein expression and mGluR3 mRNA expression were reduced in the striatum. Noticeably, prolonged EA stimulation at 100 Hz significantly reversed these changes in the striatal glutamate system. Behaviorally, EA improved the motor deficits induced by 6-OHDA lesions. Intrastriatal infusion of an mGluR2/3 antagonist APICA blocked the improving effect of EA. CONCLUSIONS: These data collectively demonstrate that the group II mGluR-mediated glutamatergic transmission in the striatum is sensitive to dopamine depletion and may serve as a substrate of EA for mediating the therapeutic effect of EA in a rat model of PD.

Electroacupuncture remediates glial dysfunction and ameliorates neurodegeneration in the astrocytic α-synuclein mutant mouse model.

BACKGROUND: The acupuncture or electroacupuncture (EA) shows the therapeutic effect on various neurodegenerative diseases. This effect was thought to be partially achieved by its ability to alleviate existing neuroinflammation and glial dysfunction. In this study, we systematically investigated the effect of EA on abnormal neurochemical changes and motor symptoms in a mouse neurodegenerative disease model. METHODS: The transgenic mouse which expresses a mutant α-synuclein (α-syn) protein, A53T α-syn, in brain astrocytic cells was used. These mice exhibit extensive neuroinflammatory and motor phenotypes of neurodegenerative disorders. In this study, the effects of EA on these phenotypic changes were examined in these mice. RESULTS: EA improved the movement detected in multiple motor tests in A53T mutant mice. At the cellular level, EA significantly reduced the activation of microglia and prevented the loss of dopaminergic neurons in the midbrain and motor neurons in the spinal cord. At the molecular level, EA suppressed the abnormal elevation of proinflammatory factors (tumor necrosis factor-α and interleukin-1ß) in the striatum and midbrain of A53T mice. In contrast, EA increased striatal and midbrain expression of a transcription factor, nuclear factor E2-related factor 2, and its downstream antioxidants (heme oxygenase-1 and glutamate-cysteine ligase modifier subunits). CONCLUSIONS: These results suggest that EA possesses the ability to ameliorate mutant α-syn-induced motor abnormalities. This ability may be due to that EA enhances both anti-inflammatory and antioxidant activities and suppresses aberrant glial activation in the diseased sites of brains.

Triptolide treatment reduces Alzheimer's disease (AD)-like pathology through inhibition of BACE1 in a transgenic mouse model of AD.

The complex pathogenesis of Alzheimer's disease (AD) involves multiple contributing factors, including amyloid ß (Aß) peptide accumulation, inflammation and oxidative stress. Effective therapeutic strategies for AD are still urgently needed. Triptolide is the major active compound extracted from Tripterygium wilfordii Hook.f., a traditional Chinese medicinal herb that is commonly used to treat inflammatory diseases. The 5-month-old 5XFAD mice, which carry five familial AD mutations in the ß-amyloid precursor protein (APP) and presenilin-1 (PS1) genes, were treated with triptolide for 8 weeks. We observed enhanced spatial learning performances, and attenuated Aß production and deposition in the brain. Triptolide also inhibited the processing of amyloidogenic APP, as well as the expression of ßAPP-cleaving enzyme-1 (BACE1) both in vivo and in vitro. In addition, triptolide exerted anti-inflammatory and anti-oxidative effects on the transgenic mouse brain. Triptolide therefore confers protection against the effects of AD in our mouse model and is emerging as a promising therapeutic candidate drug for AD.

Enhanced antidepressant-like effects of electroacupuncture combined with citalopram in a rat model of depression.

Currently, antidepressants are the dominative treatment for depression, but they have limitations in efficacy and may even produce troublesome side effects. Electroacupuncture (EA) has been reported to have therapeutic benefits in the treatment of depressive disorders. The present study was conducted to determine whether EA could enhance the antidepressant efficacy of a low dose of citalopram (an SSRI antidepressant) in the chronic unpredictable stress-induced depression model rats. Here, we show that a combined treatment with 2 Hz EA and 5 mg/kg citalopram for three weeks induces a significant improvement in depressive-like symptoms as detected by sucrose preference test, open field test, and forced swimming test, whereas these effects were not observed with either of the treatments alone. Further investigations revealed that 2 Hz EA plus 5 mg/kg citalopram produced a remarkably increased expression of BDNF and its receptor TrkB in the hippocampus compared with those measured in the vehicle group. Our findings suggest that EA combined with a low dose of citalopram could produce greater therapeutic effects, thereby, predictive of a reduction in drug side effects.

Tenuigenin attenuates α-synuclein-induced cytotoxicity by down-regulating polo-like kinase 3.

BACKGROUND AND AIMS: Tenuigenin (Ten) is a Chinese herbal extract with antioxidative and antiinflammatory effects on toxin-induced cell models of Parkinson's disease (PD); however, its effects on α-synuclein toxicity-based PD models remain unknown. α-synuclein hyperphosphorylation is a key event in PD pathogenesis and potential target of therapeutic interventions. We tested whether Ten alleviates α-synuclein-induced cytotoxicity via reducing kinases that phosphorylate α-synuclein. METHODS: SH-SY5Y cells transiently transfected with wild-type or A53T mutant α-synuclein were used to evaluate the effect of Ten on the levels of α-synuclein phosphorylation-related kinases. Cells treated with 10 µM Ten for 24 h were measured for viability (proliferation and apoptosis assays) and cellular proteins harvested and fractioned. The levels of total and phosphorylated α-synuclein and five associated kinases (polo-like kinase [PLK] 1-3, casein kinase [CK] 1-2) were evaluated by Western blotting. RESULTS: Overexpression of either wild-type or A53T mutant α-synuclein decreased cell viability and increased α-synuclein phosphorylation. Ten treatment-protected cells from this α-synuclein-induced toxicity and dramatically reduced α-synuclein phosphorylation and PLK3 (but not other kinase) levels. CONCLUSION: In α-synuclein cell model of PD, Ten is effective in attenuating α-synuclein-induced toxicity and α-synuclein phosphorylation probably via targeting PLK3, suggesting it could be an efficient therapeutic drug to treat α-synuclein-related neurodegeneration.

Inhibition of glutamate and acetylcholine release in behavioral improvement induced by electroacupuncture in parkinsonian rats.

Prior evidence shows that acupuncture improves symptoms in both Parkinson's disease (PD) patients and animal models. We examined the effects of high-frequency (100 Hz) electroacupuncture (EA) on behavior in a rat PD model induced by medial forebrain bundle (MFB) transection. Neurotransmitters levels in the striatum were measured using in vivo microdialysis and high performance liquid chromatography (HPLC). High-frequency EA stimulation at Dazhui (GV14) and Baihui (GV20) acupoints decreased rotational behavior induced by apomorphine (APO) and improved motor coordination, protected axotomized dopaminergic neurons from degeneration in the substantia nigra (SN), it did not increase striatal dopamine (DA) levels. However, EA stimulation at acupoints significantly decreased the abnormally elevated glutamate (Glu) and acetylcholine (ACh) levels in the lesioned side of striatum. Moreover, the Glu levels correlated significantly with survival ratios of dopaminergic neurons in the SNc and rotational bahavior. These data suggested that behavioral alleviation with EA stimulation may be associated with modulation of neurotransmitters release, such as Glu and ACh in the striatum, rather than with DA restoration.

The cortical and striatal gene expression profile of 100 hz electroacupuncture treatment in 6-hydroxydopamine-induced Parkinson's disease model.

Electroacupuncture (EA), especially high-frequency EA, has frequently been used as an alternative therapy for Parkinson disease (PD) and is reportedly effective for alleviating motor symptoms in patients and PD models. However, the molecular mechanism underlying its effectiveness is not completely understood. To implement a full-scale search for the targets of 100 Hz EA, we selected rat models treated with 6-hydroxydopamine into the unilateral MFB, which mimic end-stage PD. High-throughput microarray analysis was then used to uncover the regulated targets in the cortex and striatum after 4-week EA treatment. In the differentially regulated transcripts, the proportion of recovered expression profiles in the genes, the functional categories of targets in different profiles, and the affected pathways were analyzed. Our results suggested that the recovery of homeostasis in the transcript network and many regulated functional clusters in the cortex and striatum after EA treatment may contribute to the behavioral improvement of PD rats.