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The gut microbiota has been found to interact with the brain through the microbiota-gut-brain axis, regulating various physiological processes. In recent years, the impacts of the gut microbiota on neurodevelopment through this axis have been increasingly appreciated. The gut microbiota is commonly considered to regulate neurodevelopment through three pathways, the immune pathway, the neuronal pathway, and the endocrine/systemic pathway, with overlaps and crosstalks in between. Accumulating studies have identified the role of the microbiota-gut-brain axis in neurodevelopmental disorders including autism spectrum disorder, attention deficit hyperactivity disorder, and Rett Syndrome. Numerous researchers have examined the physiological and pathophysiological mechanisms influenced by the gut microbiota in neurodevelopmental disorders (NDDs). This review aims to provide a comprehensive overview of advancements in research pertaining to the microbiota-gut-brain axis in NDDs. Furthermore, we analyzed both the current state of research progress and discuss future perspectives in this field.
Subject(s)
Humans , Brain-Gut Axis , Autism Spectrum Disorder/metabolism , Brain/metabolism , Gastrointestinal Microbiome , Neurodevelopmental Disorders/metabolismABSTRACT
Objective:To preliminarily explore the association between single nucleotide polymorphisms (SNP) of five candidate genes (APH1B, PRNP, HMGCR, SIRT1, ApoE) and Alzheimer′s disease (AD), and to analyze the methylation levels of BAX and ApoE promoters on the pathogenesis of AD.Methods:Seventeen cases who were admitted to the Department of Geriatrics of the First Affiliated Hospital of Xinjiang Medical University from 2014 to 2015 and diagnosed as likely to be AD by geriatrician and neurologists according to the AD diagnostic criteria in 4th Revised Edition of the Diagnostic and Statistical Manual of Mental Disorders of the American Psychiatric Association served AD group, with an age of (75.65±5.86) years, and 34 non-AD patients with matching baseline data such as age, gender, ethnicity, and education status among patients hospitalized during the same period were selected as control group, with an age of (77.59±7.41) years. Sanger sequencing method was used for SNP typing of candidate genes. Methylation-specific polymerase chain reaction was used to determine the DNA methylation level.Results:The distribution of ApoE ε4 allele was statistically different between the AD group and the control group (χ 2=9.718, P=0.002). Candidate genes (SIRT1 rs7895833, APH1B rs1047552, PRNP rs1799990, HMGCR rs3846662) SNP locus genotypes and alleles had no statistically significant differences in the distribution between the AD group and the control group ( P>0.05). After stratification according to whether they carried ApoE ε4, no statistically significant difference was found between the two groups ( P>0.05). The BAX promoter methylation level of the AD group (0.045±0.025) was lower than that of the control group (0.061±0.028) ( t=-2.078, P=0.045). After gender stratification, the BAX methylation level of the female AD group (0.044±0.021) was lower than that of the control group (0.065±0.275) ( t=-2.230, P=0.045). There was no statistically significant difference in the methylation level of ApoE promoter between the AD group and the control group ( P>0.05). After stratification according to whether they carry ApoE ε4 or not, the methylation level of AD patients with ApoE ε4 allele (1.553±0.291) was higher than that of non-carriers (1.221±0.261) ( t=2.480, P=0.025). Conclusions:ApoE ε4 allele may be a risk factor for the onset of AD. BAX promoter hypomethylation contributes to AD in the elderly in Xinjiang, especially in female. ApoE ε4 allele may cause AD through the interaction with ApoE methylation.
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As a major cause of disability, depression is expected to become the second highest burden of disease worldwide by the year 2020. The shift of research in depression from monoamine hypothesis to the realm of neurotrophic hypothesis, neural plasticity hypothesis, and enhancing neurogenesis as an antidepressant-like agent brings about crucial insights to find novel mediator of antidepressant activity. Studies have shown that the neuropeptide VGF participates in the regulation of hippocampal neurogenesis and neuroplasticity and also plays an important role in the regulation of neuronal proliferation and survival, suggesting that the neuropeptide VGF may be a novel regulator in antidepressant treatment. The authors review the latest progress in the regulatory mechanisms of neuropeptide VGF on neurogenesis, neurotrophic and synaptic activity in depression. Further understanding of the role of neuropeptide VGF in depression can identify novel targets for pharmacological interventions.
Subject(s)
Animals , Humans , Antidepressive Agents , Depression , Neurogenesis , Neuropeptides , Physiology , Synaptic TransmissionABSTRACT
BACKGROUND: Foreign scholars use thermotherapy, a new pathway for synthetic therapy of tumor, to perform hyperpyrexia combined with chemical drug radiotherapy of intraperitoneal infiltration and metastasis or to study on the therapeutic effect of metaphase and advanced stage tumor. Especially, establishing thermal biology and thermal dosiology is a scientific and quantified track for synthetic therapy of thermal radiotherapy, thermal chemotherapy and hyperthermal perfusion of tumor.OBJECTIVE: To analyze the thermal dose effect of regional radiofrequency (RF) hyperthemia combined with radiotherapy, chemotherapy and thermal perfusion on metaphase and advanced stage tumor.DESIGN: Controlled observation.SETTING: Key Department of Traditional Chinese and Western Medicine for Tumor, the 107 Hospital of Chinese PLA (General Center for Non-traumatic Treatment and Diagnosis of Tumor).PARTICIPANTS: Totally 1 455 patients with metaphase and advanced-stage tumor admitted to the General Center for Non-traumatic Treatment and Diagnosis of Tumor, the 107 Hospital of Chinese PLA between June and September 2006 who received conservative palliative treatment in the Department of Internal Medicine were recruited in this study. They were all confirmed by pathology and imageology. ECOG was scored 2 to 4 points. Informed consents of detection and treatment were obtained from all the involved patients. The study was approved by the Hospital Ethics Committee.According to the therapeutic regimen, the patients were assigned into thermal perfusion group (n =53), thermal radiotherapy group (n =874), thermal chemotherapy group (n =458) and simple hyperthemia group (n =70).METHODS: After admission, patients in each group were performed peritoneal and pelvic cavity perfusion,intensity-modulated radiation therapy, routine chemotherapy and integrated traditional and western medicine palliative therapy, respectively. Meanwhile, they received RF hyperthemia using in vitro endogenic magnetic field hyperthermia system. A thermocouple was placed in the abdominal cavity. Temperature at 3 different sites in the abdominal cavity was collected, and meanwhile two different sites for measuring temperature at rectum and external acoustic meatus were monitored. The maximal temperature (Tmax), minimal temperature (Tmin) and the average temperature (Tave) of therapeutic target were recorded. 40 ℃/min was used as thermal dose, thermal perfusion was performed once a week, and RF hyperthemia was conducted twice a week, 60 minutes once. Target temperature was 39.5 to 43 ℃, and the thermal dose of 40 ℃/min was calculated out. Intensity-modulated radiation therapy was conducted within 1 hour before heating at (3-5)Gy/time, 3 to 4 times a week. Total dose was DT 30 to 50Gy. Thermal perfusion was conducted 2 to 3 times a week, and intensity-modulated radiation therapy was conducted once to twice a week and 6 to 8 times a course of treatment. The thermal effect of each patient was analyzed at different temperature and different diseases.MAIN OUTCOME MEASURES: ① To analyze the effect of effective thermal dose. ② To evaluate the therapeutic effect and the improvement of quality of life according to World Health Organization (WHO) objective therapeutic effect evaluation criteria and Zubrod-ECOG-WHO scores. ③To observe the changes in abdominal dropsy.RESULTS: Altogether 1 455 patients with metaphase and advanced stage participated in the final analysis. ①After perfusion, body temperature was over 39.5 ℃ in most cases after 15-minute warming, over 40.0 ℃ after another 25-minute warming, over 41.0 ℃ after additional 35-minute arming, and even to 43.0 ℃ after frequent such a thermal therapy. Temperature over 41 ℃ was found in 91 cases, at 40 ℃-40.9 ℃ in 414 cases and at 39.5 ℃-39.9 ℃ in 950 cases. ② The thermal effect of 40 ℃/min could obviously improve the therapeutic effects of graded intensity-modulated radiation therapy, low-dose chemotherapy and thermal perfusion group. The total effective rate of thermal perfusion group, thermal radiotherapy group, thermal chemotherapy group and simple hyperthemia group was 81.6%, 81.9%, 80% and 50%, respectively. The clinical therapeutic effect of 40 ℃-40.9 ℃ and 39.5 ℃-39.9 ℃ in the thermal perfusion group, thermal radiotherapy group and thermal chemotherapy group was significantly better than that in the simple hyperthemia group (P ＜ 0.05). ③ Comparison of Zubrod-ECOG-WHO score of patients before and after therapy: After therapy, Zubrod-ECOG-WHO score was enhanced in 76.3% patients. ④The changes in abdominal dropsy of patients before and after therapy: After therapy, abdominal dropsy changed in 75% patients.⑤The therapeutic effects of different diseases at different temperature: For the same disease, the therapeutic effects over 41 ℃ and at 40 ℃-40.9 ℃ were significantly different from those at 39.5 ℃-39.9 ℃(P ＜ 0.05); However, the therapeutic effects over 41 ℃ were not significantly different from those at 40 ℃-40.9 ℃ (P ＞ 0.05).CONCLUSION: ①The effects of regional RF hyperthemia combined with intensity-modulated radiation therapy are confirmed in the treatment of metaphase and advanced-stage of tumor. ② The therapeutic effects strengthen correspondingly with 40 ℃/min thermal dose increase or temperature increase.
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Objective To explore the relationship between the expressions of vascular endothelial growth factor(VEGF) and matrix metalloproteinase-9(MMP-9) in prostate cancer.Methods The expression of VEGF and MMP-9 in 148 samples of pathologically verified human prostate cancer(PCa) and 10 samples of benign prostatic hyperplasia(BPH) were detected by immunohistochemical staining.Results VEGF was overexpressed in 98 of 148 tumor tissues(66.2%) and MMP-9 was overexpressed in 58 of 148 tumor tissues(39.2%).Both of them were significantly higher than those in BPH(P0.05).But the expression of VEGF was correlated with that of MMP-9.Conclusion The expressions of VEGF and MMP-9 are closely associated with the development of prostate cancer.Therefore VEGF and MMP-9 may be clinically useful as predictor of patients'survival.
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<p><b>OBJECTIVE</b>To make an open label prospective trial for comparing the therapeutic effects of mycophenolate mofetil (MMF) vs cyclophosphamide (CYC) pulse therapy on patients with diffuse proliferative lupus nephritis (DPLN).</p><p><b>METHODS</b>Forty-six patients with biopsy proven active DPLN were enrolled in this study. Twenty-three patients were given MMF orally at a dosage of 1.0 - 1.5 g/d (MMF Group). Another 23 cases received conventional intermittent CYC pulse therapy (CYC Group). Supplemental steroid treatment was offered in the same manner to both groups. The age, sex distribution and severity of renal damage were matched in two groups. Therapeutic effects were evaluated at the end of six-month treatment. Fifteen patients in the MMF Group and 12 patients in the CYC Group had repeated renal biopsy at that time.</p><p><b>RESULTS</b>MMF therapy was more effective in reducing proteinuria and hematuria. A 50% reduction of urinary protein and urinary red blood cell excretion from baseline value in 69.6% and 91.3% patients in the MMF Group, while only 47.8% and 65.2% in the CYC Group. MMF was more effective in inhibiting autoantibody production (especially anti-dsDNA antibody) and in decreasing serum cryoglobulin levels. Pathologically, the MMF group showed more markedly reduction in glomerular immune deposits with less glomerular necrosis, and less microthrombi, less crescent formation and vascular changes in the repeated renal biopsy as compared with the CYC group. Adverse reactions related to the treatment included gastrointestinal symptoms 26.1% and 43.5% in the MMF and CYC Groups respectively, infection 17.4% in the MMF group and 30.4% in the CYC group.</p><p><b>CONCLUSION</b>MMF was more effective in controlling the clinical activity of DPLN and renal vascular lesions as compared with CYC pulse therapy in a 6 month follow-up study.</p>