Integration of microbiota and metabolomics reveals the analgesic mechanisms of emodin against neuropathic pain.

BACKGROUND AND OBJECTIVE: Neuropathic pain (NeP) induced dysbiosis of intestinal microbiota in chronic constriction injury (CCI) rats. Emodin has analgesic effect but the detailed mechanism is not clear at the present time. This study aims to explore the underling mechanism of action of emodin against NeP with in CCI model. METHODS: Male SD rats (180-220 g) were randomly divided into three groups: sham group, CCI group, and emodin group. Behavioral tests were performed to evaluate the therapeutic effects of emodin on CCI model. Feces and spinal cords of all rats were collected 15 days after surgery. 16S rDNA sequencing, untargeted metabolomics, qPCR and ELISA were performed. RESULTS: Mechanical withdrawal thresholds (MWT), thermal withdrawal latency (TWL) and Sciatic functional index (SFI) in emodin group were significantly higher than CCI group (P < 0.05). Emodin not only inhibited the expression of pro-inflammatory cytokines in the spinal cords and colonic tissue, but also increased the expression of tight junction protein in colonic tissue. 16S rDNA sequencing showed that emodin treatment changed the community structure of intestinal microbiota in CCI rats. Untargeted metabolomics analysis showed that 33 differential metabolites were screened out between CCI group and emodin group. After verification, we found that emodin increased the level of S-adenosylmethionine (SAM) and Histamine in the spinal cord of CCI rats. CONCLUSION: Emodin was effective in relieving neuropathic pain, which is linked to inhibition inflammatory response, increasing the proportion of beneficial bacteria and beneficial metabolites.

TNEA therapy promotes the autophagic degradation of NLRP3 inflammasome in a transgenic mouse model of Alzheimer's disease via TFEB/TFE3 activation.

BACKGROUND: The impairment in the autophagy-lysosomal pathway (ALP) and the activation of NLR family pyrin domain containing 3 (NLRP3) inflammasome represent two molecular events leading to neurodegeneration and neuroinflammation in Alzheimer's disease (AD), a devastating neurodegenerative disorder without a cure. Previously we demonstrated the cognitive-enhancing effect of a combined electroacupuncture (EA) therapy termed TNEA in a transgenic mouse model of AD, involving activation of transcription factor EB (TFEB), a master regulator of ALP. However, whether and how TNEA inhibits NLRP3 inflammasome via TFEB-mediated ALP in AD remains to be investigated. METHODS: 5xFAD mice overexpressing amyloid-ß (Aß) were treated with TNEA or EA on its composing acupoints (GB13 and GV24). The changes in the signaling pathways regulating NLRP3 inflammasome, the association of NLRP3 inflammasome with ALP, and the roles of TFEB/TFE3 in mice brains were determined by immunoblots, immunohistochemistry and AAV-mediated knockdown assays. RESULTS: TNEA inhibits the activation of NLRP3 inflammasome and the release of active interleukin 1ß (IL1B) in the hippocampi of 5xFAD mice. Mechanistically, TNEA promoted the autophagic degradation of inflammasome components via activating both TFEB and TFE3 by modulating kinases including AMPK and AKT. The composing acupoints in TNEA showed synergistic effects on regulating these molecular events and memory improvement. CONCLUSION: Our findings suggest that TNEA attenuates AD-associated memory impairment via promoting TFEB/TFE3-mediated autophagic clearance of Aß and NLRP3 inflammasome, and partially reveal the molecular basis of combined acupoints therapy originated from ancient wisdom.

Bibliometric review of 1992-2022 publications on acupuncture for cognitive impairment.

Objective: To explore the development context, research hotspots, and frontiers of acupuncture therapy for cognitive impairment (CI) from 1992 to 2022 by visualization analysis. Methods: Articles about acupuncture therapy for cognitive impairment were retrieved from the Web of Science Core Collection (WoSCC) until 1 March 2022. Basic information was collected by Excel 2007, and VOSviewer 1.6.17 was used to analyze the co-occurrence of countries, institutes, and authors. Co-citation maps of authors and references were analyzed by CiteSpace V.5.8.R3. In addition, CiteSpace was used to analyze keyword clusters and forecast research frontiers. Results: A total of 279 articles were retrieved, including articles from 19 countries, 334 research institutes, and 101 academic journals. The most published country and institutes were the People's Republic of China (217) and the Fujian University of Traditional Chinese Medicine (40). Ronald C Petersen owned the highest co-citations (56). Keywords and co-cited references cluster showed the main research directions in this area, including "ischemic stroke," "cerebral ischemia/reperfusion," "mild cognitive impairment," "Alzheimer's disease," "vascular dementia," "vascular cognitive impairment with no dementia," "multi-infarct dementia," "synaptic injury," "functional MRI," "glucose metabolism," "NMDA," "nuclear factor-kappa b pathway," "neurotrophic factor," "matrix metalloproteinase-2 (MMP-2)," "tumor necrosis factor-alpha," "Bax," "Caspase-3," and "Noxa". Trending keywords may indicate frontier topics, such as "randomized controlled trial," "rat model," and "meta-analysis." Conclusion: This research provides valuable information for the study of acupuncture. Diseases focus on mild cognitive impairment (MCI), Alzheimer's disease (AD), and vascular dementia (VaD). Tauopathies with hyperphosphorylation of Tau protein as the main lesions also need to be paid attention to. The development of functional magnetic resonance imaging (fMRI) will better explain the therapeutic effect of acupuncture treatment. The effect of acupuncture on a single point is more convincing, and acupuncture on Baihui (GV20) may be needed in the future. Finally, the implementation of high-quality multicenter randomized controlled trials (RCTs) requires increased collaboration among experts from multiple fields and countries.

The role of microbiota in autism spectrum disorder: A bibliometric analysis based on original articles.

Background: Gastrointestinal (GI) symptoms can be observed in autism spectrum disorder (ASD) children. It is suggested that the gut microbiota and its metabolites are associated, not only with GI symptoms, but also with behaviors of ASD. The aim of this study was to explore the development context, research hotspots and frontiers of gut microbiota and ASD from January 1, 1980 to April 1, 2022 by bibliometric analysis. Materials and methods: Publications of ASD and gut microbiota research from 1 January 1980 to 1 April 2022 were retrieved from the Web of Science Core Collection (WoSCC). Publications and citations trends were analyzed by Excel 2010. CiteSpace was used to analyze countries/regions, authors, institutes, references, and keywords and to visualize the knowledge map. Results: A total of 1027 studies were retrieved, and 266 original articles were included after screening. The most published countries and institutes were the United States and King Saud University. Afaf El-Aansary published the most articles, while Finegold SM had the highest co-citations. Hotspots and emerging trends in this area may be indicated by co-cited references and keywords and their clusters, including "gut-brain axis," "behavior," "chain fatty acid," "brain," "feces," "propionic acid," "clostridium perfringens," and "species clostridium innocuum." Conclusion: The United States dominants the research in this field, which focuses on the alterations of gut microbiota composition and its metabolites, among which the roles of the genus Clostridium and metabolites of short-chain fatty acids, especially propionic acid, are priorities. Fecal microbiota transplantation (FMT) is a promising complementary therapy. In general, research in this area is sparse, but it still has great research prospects.

Knowledge mapping analysis of mental health research on COVID-19.

Objective: A bibliometric analysis of COVID-19 is conducted to examine the developmental context, research hotspots, and frontiers of mental health. Methods: Using the Web of Science Core Collection (WOSCC), we have retrieved articles on mental health research related to COVID-19 which were published between 2019 and 2021. The coauthorship of countries, institutes, and authors was analyzed using VOSviewer 1.6.17, and the co-citation map of authors/references was analyzed as well. CiteSpace version 5.8.R3 was used to analyze keyword clusters and forecast research frontiers. Results: There were 8,856 articles retrieved, including 10,559 research institutes and 1,407 academic journals. The most published country and institutes were the United States (2190) and the University of London (373). Wang, Chengyu owned the highest co-citations (1810). Frontier topics can be identified by trending keywords, including "anxiety," "depression," "psychological distress," "quarantine," "post-traumatic stress disorder (PTSD)," "insomnia," and "Healthcare workers." Conclusion: The most common psychological problems of people during the epidemic are anxiety and depression. Insomnia and PTSD need to be solved under the normalization of the epidemic. GAD-7 and PHQ-9 scales are the most convenient and effective for screening anxiety and depression. Healthcare workers, older adults, and college students should be concerned, and social and family support is essential.

Research Hotspots and Trends Analysis of TFEB: A Bibliometric and Scientometric Analysis.

Objective: To explore the development context, research hotspots and frontiers of Transcription factor EB (TFEB) from 1991 to 2021 by bibliometric analysis. Methods: Publications about TFEB research from 1991 to 2021 were retrieved from the Web of Science Core Collection (WoSCC). Excel 2007 was used to collect basic information, including publications, research areas. VOSviewer 1.6.17 was used to analyze co-authorship of countries, institutes and authors. Co-citation of cited authors, cited references were analyzed by CiteSpace V.5.8.R3. In addition, CiteSpace was used to analyze keywords cluster and forecast research frontiers. Results: A total of 1,059 literatures were retrieved, including 1,340 research institutes and 393 academic journals. The main area of research related to TFEB is biology (340), the most published country and institutes were the United States (487) and Baylor College of Medicine (70). Settembre C owned the highest co-citations (663). Trending keywords may indicate frontier topics, including "Alzheimer's disease," "Parkinson's disease," "(p21; q12)," "melanoma," "pancreatic cancer," "breast cancer," "calcineurin," "TFE3," "trehalose," and "curcumin." Conclusion: This research provides valuable information for the study of TFEB. Disease research focuses more on neurodegenerative diseases (NDs) and tumors. Trehalose and curcumin are novel agents acting on TFEB. Rap-TRPML1-Calcineurin-TFEB and TFE3 are increasing signal pathway researches, similarly, the molecular biological mechanism of TFEB needs further exploration.

Clinical therapeutic effects of probiotics in patients with constipation associated with Parkinson disease: A protocol for systematic review and meta-analysis.

BACKGROUND: Constipation is the most predominant symptom of Parkinson disease (PD), preceding the occurrence of motor symptoms in some patients, leading to reduced quality of life (QOL). The general approaches for the treatment have some side effects, but probiotics are live or attenuated microorganisms attributed to ameliorating constipation effects. Moreover, as treatments are generally well tolerated and side effects are scarce, there is room for further research. Therefore this work aims at investigating the clinical effectiveness and safety of probiotics for constipation in PD. METHODS: Published RCTs will be retrieved by searching Medline, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), VIP, Wan Fang database, and China Biology Medicine Database (complete bowel movement), which will be searched from establishment of the database to October 10, 2021. Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) guidelines are used to design this protocol. RevMan V.5.3 software will be used for meta-analysis, risk of bias will be assessed by the Cochrane Collaboration tool and the collected evidence will be narratively synthesized. We will also perform a meta-analysis to pool estimates from studies considered to be homogenous. Subgroup analyses will be based on intervention or overall bias. CONCLUSION: The meta-analysis will assess the effectiveness and safety of using probiotics to treat and heal the constipation of PD. ETHICS AND DISSEMINATION: Ethics approval is unrequired. REGISTRATION NUMBER: CRD42021276215.

Auricular acupressure promotes uterine involution after cesarean section: A randomized controlled trial.

BACKGROUND: Postpartum subinvolution of the uterus is a more common condition after cesarean section. Auricular acupressure (AA) is widely used for the treatment of postpartum diseases. However, few studies have explored the effects of AA as a treatment of uterine involution following cesarean section to date. This study aimed to assess the efficacy and safety of AA for uterine involution after cesarean section. METHODS: A total of 109 women who underwent cesarean section participated in this study. They were randomly allocated to either real AA or sham AA in a 1:1 ratio by a computer program. For 3 days, the real AA and sham AA groups received treatment 3 times daily. A series of assessments at 42 days after cesarean section, namely on the uterine size, the incidence of hydrometra, the first anal exsufflation time, bleeding volume at 6 hours, bleeding volume at 6-24 hours along with other general assessments were carried out. RESULTS: A total of 89 women completed the study. The uterine size at 42 days after a cesarean section was 6.3 cm smaller in the real AA group than in the sham AA group (P < 0.01). The incidence of hydrometra on day 42 postpartum was lower in the real AA group than in the sham AA group (P < 0.01). The lochia duration and the first anal exsufflation time after cesarean section were shorter in the real AA group than in the sham AA group (P < 0.05). CONCLUSION: AA improves uterine involution after cesarean section. TRIAL REGISTRATION: ChiCTR1800015569.

Clinical evidence of acupuncture and related therapy in patients with cancer-pain: A protocol for systematic review and meta-analysis.

BACKGROUND: Cancer pain (CP) is one of the common complications of cancer. During the treatment, oral medication, radiotherapy and chemotherapy bring certain adverse reactions to patients with CP; a safe way to treat this disease is necessary. Acupuncture and related therapies for CP with few side effects have been gradually accepted. But at present the evidence is insufficient, the related research is not thorough enough. The purpose of this study was to investigate the efficacy and safety of acupuncture and related therapies for CP. METHODS: The Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) guidelines were used to design this protocol. The final study will also be conducted under the PRISMA guidelines for systematic reviews and meta-analysis. An electronic search will be conducted in Medline, Embase, and the Cochrane Central Register of Controlled Trials databases through January 2020. The search will be conducted in English. Risk of bias will be assessed by the Cochrane Collaboration tool and the collected evidence will be nar-ratively synthesized. We will also perform a meta-analysis to pool estimates from studies considered to be homogenous. Subgroup analyses will be based on intervention or overall bias. The strength of evidence will be evaluated by the Grading of Recommendations, Assessment, Development and Evaluation scale. RESULTS: This systematic review will summarize high quality clinical evidence to assess and appraise the effectiveness and safety of acupuncture and related therapies for CP patients. CONCLUSION: The meta-analysis will assess evidence from randomized controlled trials of acupuncture and related therapies and CP types. INPLASY REGISTRATION NUMBER: INPLASY202040129.