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CONTEXT: Cachexia is associated with poor survival rates. In the clinical setting, the diagnosis of cancer cachexia is challenging. The cachexia index (CXI), a new index for predicting survival time, is a promising tool for diagnosing cancer cachexia; however, its efficacy in predicting patient survival has not been validated. OBJECTIVE: This meta-analysis and systematic review aimed to explore the CXI's prognostic value in patients with cancer. DATA SOURCES: The PubMed, Embase, MEDLINE, and Cochrane Library databases were searched for relevant studies to determine the association between CXI findings and prognosis. DATA EXTRACTION: The outcomes were overall survival (OS), progression-, disease-, and recurrence-free survival (PFS/DFS/RFS) rates, and the rate of complete response. DATA ANALYSIS: The QUality In Prognostic Studies (QUIPS) tool was used to evaluate the quality of the included trials. This meta-analysis comprised 14 studies involving 2777 patients. A low CXI was associated with decreased OS (hazard ratio [HR] 2.34, 95% confidence interval [CI] 2.01-2.72; P < .001), PFS/DFS/RFS (HR 1.93, 95% CI 1.68-2.22; P < .001), and complete response (odds ratio [OR] 0.49, 95% CI 0.36-0.66; P < .001). Patients with a low CXI had a lower body mass index (mean difference [MD] -0.75, 95% CI -1.00 to 0.50; P < .001), skeletal muscle index (standardized MD -0.80, 95% CI -0.98 to -0.61; P < .001), and serum albumin level (MD -0.23, 95% CI -0.26 to -0.20; P < .001); and a higher neutrophil-lymphocyte ratio (MD 1.88, 95% CI 1.29-2.47; P < .001) and more advanced disease stages (OR 0.80, 95% CI 0.71-0.91; P = .001). CONCLUSION: A low CXI was found to be associated with poor survival in patients with cancer. While the CXI is a promising marker for predicting cancer cachexia, further studies are required to verify its usefulness.
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Background: The eradication regimen for Helicobacter pylori (H. pylori) infection can induce gut dysbiosis. In this open-label, prospective, and randomized clinical trial, we aimed to assess the effects of fucoidan supplementation on the eradication rate and gut microbial homeostasis in the context of quadruple therapy, as well as to investigate the combined effects of fucoidan and synbiotics supplementations. Methods: Eighty patients with H. pylori infection were enrolled and randomly assigned to one of four treatment groups: the QT (a 2-week quadruple therapy alone), QF (quadruple therapy plus a 6-week fucoidan supplementation), QS (quadruple therapy plus a 6-week synbiotics supplementation), and QFS (quadruple therapy with a 6-week fucoidan and synbiotics supplementation), with 20 patients in each group. The QT regimen included rabeprazole, minocycline, amoxicillin, and bismuth potassium citrate. The synbiotics supplementation contained three strains of Bifidobacterium, three strains of Lactobacillus, along with three types of dietary fiber. All of the patients underwent 13C-urea breath test (13C-UBT) at baseline and at the end of the 6th week after the initiation of the interventions. Fresh fecal samples were collected at baseline and at the end of the 6th week for gut microbiota analysis via 16S rRNA gene sequencing. Results: The eradication rates among the four groups showed no significant difference. In the QT group, a significant reduction in α-diversity of gut microbiota diversity and a substantial shift in microbial composition were observed, particularly an increase in Escherichia-Shigella and a decrease in the abundance of genera from the Lachnospiraceae and Ruminococcaceae families. The Simpson index was significantly higher in the QF group than in the QT group. Neither the QS nor QFS groups exhibited significant changes in α-diversity or ß-diversity. The QFS group was the only one that did not show a significant increase in the relative abundance of Escherichia-Shigella, and the relative abundance of Klebsiella significantly decreased in this group. Conclusion: The current study provided supporting evidence for the positive role of fucoidan and synbiotics supplementation in the gut microbiota. The combined use of fucoidan and synbioticss might be a promising adjuvant regimen to mitigate gut dysbiosis during H. pylori eradication therapy.
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INTRODUCTION: The imbalance in gut microbiota is contributing to the development and progression of IBS. FMT can improve the gut microbiota, and donor-recipient-matched FMT can help develop individualised treatment plans according to different enterotypes. This study aimed to explore the efficacy of donor-recipient matched FMT in IBS-D and evaluate its effects on gut microbiota. METHODS: Twenty-seven patients with IBS-D were randomly divided into donor-recipient matched FMT group (Group P), random-donor FMT group (Group R) and placebo group (Group B). All participants received corresponding FMT treatment after filling in IBS-S, IBS-QoL, GSRS, HADS questionnaires and having their stool samples collected at 4, 8 and 12 weeks after treatment. Analysed the improvement in the symptoms and the changes in the bacterial flora fo three groups. RESULTS: 1. The IBS-SSS, IBS-Qol, GSRS and anxiety scores of Group P were significantly lower after treatment(Pï¼0.05). The IBS-Qol scores of Group R was significantly lower after treatment(Pï¼0.05). 2. Beta diversity analysis showed that the gut microbiota of Group P had an obvious trend of classification after treatment. 3. Seven bacterial genera were related to the differences in the IBS-SSS scores before and after treatment. CONCLUSION: Donor-recipient-matched FMT significantly improved the clinical symptoms, quality of life, and anxiety scores of the patients with IBS-D than random-donor FMT.
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BACKGROUND: WHO stated the environment is an important factor affecting the development of hospice care. The environment is the sum of factors affecting behavior besides the individual factors. Currently, a scale to comprehensively assess the hospice environment of nurse is still lacking. This study aimed to develop an instrument to investigate the environmental factors affecting hospice care of nurses. METHODS: Literature review and a semi-structured interview were conducted to form the items pool of the Hospice Care Environment Scale. Two rounds of Delphi expert consultation were conducted by 16 experts to revise the scale dimensions and entries to form the Hospice Care Environment Scale. A psychometric evaluation was then performed among 530 oncology nurses in a large tertiary oncology hospital in Hubei Province. The 500 valid questionnaires were randomly divided into two groups in a 1:1 ratio, sample 1 (n1 = 250) for item screening and sample 2 (n2 = 250) for quality evaluation of the resulting scale. Item analysis, reliability analysis, validity analysis and acceptability analysis were performed. RESULT: The Hospice Care Environment Scale consists of two dimensions and 13 entries. The Cronbach's α coefficient of the Hospice Care Environment Scale was 0.970, and the Cronbach's α coefficient of the two dimensions were 0.952 and 0.969, respectively, with the Item-content validity index and average Scale- content validity index of the scale was both 1.000. The validation factor analysis showed the standardized path coefficients of each item were basically above 0.5, and the factor structure model was stable and suitable. The average completion time of the scale was about 3 min, which had good feasibility. CONCLUSION: The Hospice Care Environment Scale to assess the environment of hospice care services, has good content and construct validity and reliability. This scale can provide guidance to evaluate the hospice care environment.
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Méthode Delphi , Accompagnement de la fin de la vie , Psychométrie , Humains , Reproductibilité des résultats , Psychométrie/instrumentation , Psychométrie/méthodes , Enquêtes et questionnaires , Accompagnement de la fin de la vie/normes , Accompagnement de la fin de la vie/méthodes , Femelle , Mâle , Adulte , Adulte d'âge moyen , ChineRÉSUMÉ
This study aimed to investigate the effect of Broussonetia papyrifera polysaccharides (BPP) on the jejunal intestinal integrity of rats ingesting oxidized fish oil (OFO) induced oxidative stress. Polysaccharides (Mw 16,956 Da) containing carboxyl groups were extracted from Broussonetia papyrifera leaves. In vitro antioxidant assays showed that this polysaccharide possessed antioxidant capabilities. Thirty-two male weaned rats were allocated into two groups orally infused BPP solution and PBS for 26 days, respectively. From day 9 to day 26, half of the rats in each group were fed food containing OFO, where the lipid peroxidation can induce intestinal oxidative stress. OFO administration resulted in diarrhea, decreased growth performance (p < 0.01), impaired jejunal morphology (p < 0.05) and antioxidant capacity (p < 0.01), increased the levels of ROS and its related products, IL-1ß and IL-17 (p < 0.01) of jejunum, as well as down-regulated Bcl-2/Bax (p < 0.01) and Nrf2 signaling (p < 0.01) of jejunum in rats. BPP gavage effectively alleviated the negative effects of OFO on growth performance, morphology, enterocyte apoptosis, antioxidant capacity and inflammation of jejunum (p < 0.05) in rats. In the oxidative stress model cell assay, the use of receptor inhibitors inhibited the enhancement of antioxidant capacity by BPP. These results suggested that BPP protected intestinal morphology, thus improving growth performance and reducing diarrhea in rats ingesting OFO. This protective effect may be attributed to scavenging free radicals and activating the Nrf2 pathway, which enhances antioxidant capacity, consequently reducing inflammation and mitigating intestinal cell death.
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Antioxydants , Broussonetia , Stress oxydatif , Feuilles de plante , Polyosides , Animaux , Stress oxydatif/effets des médicaments et des substances chimiques , Polyosides/pharmacologie , Polyosides/composition chimique , Rats , Mâle , Feuilles de plante/composition chimique , Antioxydants/pharmacologie , Broussonetia/composition chimique , Jéjunum/effets des médicaments et des substances chimiques , Jéjunum/métabolisme , Jéjunum/anatomopathologie , Intestins/effets des médicaments et des substances chimiques , Intestins/anatomopathologie , Régime alimentaire , Modèles animaux de maladie humaine , Muqueuse intestinale/effets des médicaments et des substances chimiques , Muqueuse intestinale/métabolisme , Muqueuse intestinale/anatomopathologie , Espèces réactives de l'oxygène/métabolisme , Rat Sprague-Dawley , Peroxydation lipidique/effets des médicaments et des substances chimiquesRÉSUMÉ
Hepatocellular carcinoma (HCC) is a prevalent and deadly form of cancer globally with typically unfavorable outcomes. Increasing research suggests that lactate serves as an important carbon contributor to cellular metabolism and holds a crucial part in the progression, sustenance, and treatment response of tumors. However, the contribution of lactate-related genes (LRGs) in HCC is still unclear. In this study, we analyzed TCGA datasets and screened 21 differentially expressed LRGs related to long-term survivals in HCC patients. Pan-cancer assays revealed that 21 LRGs expression exhibited a dysregulated level in man types of tumors and associated with clinical prognosis of tumor patients. The analysis of 21 LRGs successfully classified HCC samples into two molecular subtypes, and these two subtypes showed significant differences in clinical information, gene expression, and immune characteristics. Subsequently, based on the aforementioned 21 LRGs, a novel prognostic signature (DTYMK, IRAK1, POLRMT, MPV17, UQCRH, PDSS1, SLC16A3, SPP1 and LDHD) was generated by LASSO-Cox regression analysis. Survival assays demonstrated that the signature performed well in predicting the overall survival of patients with HCC. The results of Gene Set Variation Analysis indicated that the high GSVA scores were associated with poor prognosis. Moreover, we also investigated the correlation between GSVA scores and various signaling pathways in HCC. Among the nine prognostic genes, our attention focused on POLRMT which was highly expressed in HCC specimens based on TCGA datasets and several HCC cell lines. In addition, functional assays indicated that POLRMT distinctly promoted the proliferation, migration and energy metabolism of HCC cells via regulating Wnt/ß-Catenin signaling. Overall, through the establishment of a novel prognostic signature, we have provided potential clinical value for assessing the prognosis of HCC patients. Furthermore, our study has identified the high expression of POLRMT in HCC and demonstrated its crucial role in HCC cell proliferation. These findings hold great importance in advancing our understanding of the pathophysiology of HCC, identifying new therapeutic targets, and improving patient survival rates.
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Sensor degradation and failure often undermine users' confidence in adopting a new data-driven decision-making model, especially in risk-sensitive scenarios. A risk assessment framework tailored to classification algorithms is introduced to evaluate the decision-making risks arising from sensor degradation and failures in such scenarios. The framework encompasses various steps, including on-site fault-free data collection, sensor failure data collection, fault data generation, simulated data-driven decision-making, risk identification, quantitative risk assessment, and risk prediction. Leveraging this risk assessment framework, users can evaluate the potential risks of decision errors under the current data collection status. Before model adoption, ranking risk sensitivity to sensor data provides a basis for optimizing data collection. During the use of decision algorithms, considering the expected lifespan of sensors enables the prediction of potential risks the system might face, offering comprehensive information for sensor maintenance. This method has been validated through a case study involving an access control.
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This study isolated and purified a novel homogeneous arabinogalactan polysaccharide from Yucca schidigera extract (YSE), unveiled its unique structure and explored its antioxidant function. Firstly, the antioxidant potential of YSE was demonstrated in piglet trials. A homogeneous polysaccharide with a molecular weight of 24.2 kDa, designated as Yucca schidigera polysaccharide B (YPB), was isolated and purified from YSE. The monosaccharide composition of YPB was Rha, Araf, Galp, and Glcp, whose molar percentages were 2.8 %, 11.6 %, 45.5 %, and 40.0 %, respectively. Methylation analysis combined with 1D and 2D nuclear magnetic resonance showed that YPB was a complex polysaccharide with a main glycosidic linkage pattern of â2)-α-Ê-Rha-(1 â 3)-ß-á´ -Galp-(1â3)-ß-á´ -Galp-(1 â 3)-ß-á´ -Galp-(1 â 3)-ß-á´ -Glcp-(1â, and branched Araf and Galp fragments were connected with the main chain through â3,6)-ß-á´ -Galp-(1â, â3,4)-ß-á´ -Glcp-(1â, and â2,4)-α-Ê-Rha-(1â linkages. Following the in vitro biochemical assays of bioactive components, YPB should be the contributor to the antioxidant activity in YSE. Based on the establishment of oxidative stress model, YPB exhibited strong antioxidant capacity and activated NRF2 pathway, and then provided protection against the damage induced oxidative stress in IPEC-J2 cells and rats. Further analysis with inhibitors found that this antioxidant effect was attributed to its interaction with epidermal growth factor receptor and mannose receptor, and stimulating PI3K/AKT pathway.
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Antioxydants , Yucca , Suidae , Animaux , Rats , Antioxydants/composition chimique , Yucca/composition chimique , Phosphatidylinositol 3-kinases , Polyosides/composition chimiqueRÉSUMÉ
Purpose: The aim is to investigate the application value of dermoscopy combined with reflectance confocal microscopy (RCM) in assessing vitiligo disease activity and treatment response. Patients and Methods: We enrolled 279 patients with vitiligo and evaluated the disease activity by Vitiligo Disease Activity (VIDA) score, dermoscopy, RCM and dermoscopy combined with RCM respectively. The sensitivity and specificity of different assessment techniques were compared with VIDA score by the differences and consistency. The different characteristics of dermoscopy and RCM with different treatment responses were also analyzed. Results: The results showed that the sensitivity and specificity of dermoscopy combined RCM were higher than RCM or dermoscopy alone (P values less than 0.05). In the repigmentation process, leukotrichia, pigment network absent and perilesional hyperpigmentation under dermoscopy at the baseline suggested a poor treatment response, while the incompletely disappearing pigment rings under RCM and perifollicular hyperpigmentation under dermoscopy indicated a good treatment response. We also found the proportion of patients with telangiectasia, increased pigment at the lesions and around the hair follicles was significantly higher in the good treatment response group than that in the poor one by dermoscopy (χ2 = 4.423, 32.471, 4.348, P = 0.035 0.000, 0.037) and by RCM the proportion of patients with both increased pigment granules and dendritic melanocytes in the good treatment response group was higher than that in the poor one (χ2 = 38.215, 5.283, P = 0.000, 0.022, respectively). Conclusion: With the higher sensitivity and specificity than dermoscopy or RCM alone, a combination of dermoscopy and RCM may be a new more accurate measure to assess the vitiligo disease activity and the treatment response.
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Splitting tensile strength (STS) is an important mechanical property of concrete. Modeling and predicting the STS of concrete containing Metakaolin is an important method for analyzing the mechanical properties. In this paper, four machine learning models, namely, Artificial Neural Network (ANN), support vector regression (SVR), random forest (RF), and Gradient Boosting Decision Tree (GBDT) were employed to predict the STS. The comprehensive comparison of predictive performance was conducted using evaluation metrics. The results indicate that, compared to other models, the GBDT model exhibits the best test performance with an R2 of 0.967, surpassing the values for ANN at 0.949, SVR at 0.963, and RF at 0.947. The other four error metrics are also the smallest among the models, with MSE = 0.041, RMSE = 0.204, MAE = 0.146, and MAPE = 4.856%. This model can serve as a prediction tool for STS in concrete containing Metakaolin, assisting or partially replacing laboratory compression tests, thereby saving costs and time. Moreover, the feature importance of input variables was investigated.
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BACKGROUND: Iron plays a pivotal role in various physiological processes, including intestinal inflammation, ferroptosis, and the modulation of the gut microbiome. However, the way these factors interact with each other is unclear. METHODS: Mice models were fed with low, normal and high iron diets to assess their impacts on colitis, ferroptosis and gut microbiota. Untargeted fecal metabolomics analysis, 16S rRNA sequencing, histopathology analysis, real-time quantitative PCR and western blot were performed to analyze the differences in the intestinal inflammatory response and understanding its regulatory mechanisms between low, normal and high iron groups. RESULTS: The iron overload changed the serum iron, colon iron and fecal iron. In addition, the iron overload induced the colitis, induced the ferroptosis and altered the microbiome composition in the fecal of mice. By using untargeted fecal metabolomics analysis to screen of metabolites in the fecal, we found that different metabolomics profiles in the fecal samples between iron deficiency, normal iron and iron overload groups. The correlation analysis showed that both of iron deficiency and overload were closely related to Dubosiella. The relationship between microbial communities (e.g., Akkermansia, Alistipes, and Dubosiella) and colitis-related parameters was highly significant. Additionally, Alistipes and Bacteroides microbial communities displayed a close association with ferroptosis-related parameters. Iron overload reduced the concentration of metabolites, which exert the anti-inflammatory effects (e.g., (+)-.alpha.-tocopherol) in mice. The nucleotide metabolism, enzyme metabolism and metabolic diseases were decreased and the lipid metabolism was increased in iron deficiency and iron overload groups compared with normal iron group. CONCLUSION: Iron overload exacerbated colitis in mice by modulating ferroptosis and perturbing the gut microbiota. Iron overload-induced ferroptosis was associated with NRF2/GPX-4 signaling pathway. Specific microbial taxa and their associated metabolites were closely intertwined with both colitis and ferroptosis markers.
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Colite , Ferroptose , Microbiome gastro-intestinal , Carences en fer , Surcharge en fer , Animaux , Souris , ARN ribosomique 16S , Colite/induit chimiquement , Fer , Bacteroidetes , Firmicutes , Souris de lignée C57BLRÉSUMÉ
OBJECTIVES: Numerous genome-wide association studies have identified CACNA1C as one of the top risk genes for schizophrenia. As a necessary post-genome-wide association study (GWAS) follow-up, here, we focused on this risk gene, carefully investigated its novel risk variants for schizophrenia, and explored their potential functions. METHODS: We analyzed four independent samples (including three European and one African-American) comprising 5648 cases and 6936 healthy subjects to identify replicable single nucleotide polymorphism-schizophrenia associations. The potential regulatory effects of schizophrenia-risk alleles on CACNA1C mRNA expression in 16 brain regions (nâ =â 348), gray matter volumes (GMVs) of five subcortical structures (nâ =â 34â 431), and surface areas and thickness of 34 cortical regions (nâ =â 36â 936) were also examined. RESULTS: A novel 17-variant block across introns 36-45 of CACNA1C was significantly associated with schizophrenia in the same effect direction across at least two independent samples (1.8â ×â 10-4â ≤â Pâ ≤â 0.049). Most risk variants within this block showed significant associations with CACNA1C mRNA expression (1.6â ×â 10-3â ≤â Pâ ≤â 0.050), GMVs of subcortical structures (0.016â ≤â Pâ ≤â 0.048), cortical surface areas (0.010â ≤â Pâ ≤â 0.050), and thickness (0.004â ≤â Pâ ≤â 0.050) in multiple brain regions. CONCLUSION: We have identified a novel and functional risk variant block at CACNA1C for schizophrenia, providing further evidence for the important role of this gene in the pathogenesis of schizophrenia.
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Étude d'association pangénomique , Schizophrénie , Humains , Introns/génétique , Schizophrénie/génétique , Allèles , ARN messager , Canaux calciques de type L/génétiqueRÉSUMÉ
BACKGROUND: Irritable bowel syndrome (IBS) is one of the most common functional bowel disorders, but its pathogenesis remains unknown. Its development may be linked to intestinal dysmetabolism, directly and indirectly. The present study aimed to screen the differentially expressed small molecular substances in the mucosa of the colon between IBS with diarrhea (IBS-D) patients and healthy subjects and explore the pathogenesis of IBS-D. METHODS: In this pilot study, the metabolites of colonic mucosa in ten patients with IBS-D and six healthy controls (HC) were analyzed by DESI-MSI. We also mapped the spatial distribution of the screened differential metabolites from samples of the IBS-D group and HC group. RESULTS: The results showed that 20 metabolites in the colonic mucosa of IBS-D were significantly more abundant, while the other 77 substances were significantly reduced. Enrichment analysis of 97 differential metabolites and KEGG pathway analysis revealed that six medium-chain and long-chain fatty acids were determined to be most overrepresented in the IBS-D group compared to the HC group. Four of these six fatty acids are all PUFAs. The DESI-MSI results suggested that these fatty acids were localized in the colonic mucosa and confirmed the differences in these fatty acids between IBS-D and HC. CONCLUSIONS: Medium-chain and long-chain fatty acids localized in the colonic mucosa are likely to be potential indicators for the differentiation of IBS-D from healthy subjects which may have implications in the mechanisms and possible preventive measures against IBS. CLINICAL TRIAL REGISTRY REGISTRATION NUMBER: ChiCTR2200060224.
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Dravet syndrome (DS), previously known as severe myoclonic epilepsy in infancy (SMEI), is considered the most serious "epileptic encephalopathy." Here, we present a man with a de novo SCN1A mutation who was diagnosed with DS at the age of 29. In addition to pharmaco-resistant seizures and cognitive delay, he also developed moderate to severe motor and gait problems, such as crouching gait and Pisa syndrome. Moreover, it deteriorated significantly following an epileptic seizure. The patient presented with severe flexion of the head and trunk in the sagittal plane and fulfilled the diagnostic criteria for camptocormia and antecollis. After a week, it spontaneously alleviated partially. We applied levodopa to the patient and had a good response. Functional Gait Assessment (FGA) was assessed at three different times: 4 days after the seizure, 1 week after the seizure, and after taking levodopa for 2 years. The results were 4, 12, and 19 points, respectively. We postulated that: (1) gait and motor deficits are somehow influenced by recurrent epileptic episodes;(2) the nigrostriatal dopamine system is involved. To our knowledge, we were the ones who first reported this phenomenon.
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Épilepsies myocloniques , Épilepsie , Mâle , Humains , Adulte , Lévodopa/génétique , Canal sodique voltage-dépendant NAV1.1/génétique , Mutation , Épilepsies myocloniques/génétique , Crises épileptiques/génétique , DémarcheRÉSUMÉ
Objective: To compare and analyze the mucosal metabolites and mucosal microbiota of different parts of colon in patients with IBS. Methods: A total of 10 patients with IBS-D and six healthy controls (HC) were enrolled. All enrolled participants underwent two biopsies of the ileocecal and sigmoid colon during colonoscopy. Metabolomic profiling of one piece of tissue was conducted using desorption electrospray ionization-mass spectrometry (DESI-MS), and the gut flora of the other piece was examined using 16S rRNA sequencing. The metabolic profiles and flora of the ileocecal and sigmoid colonic mucosa in each group were further analyzed in this study. Results: (1) Principal components analysis (PCA) indicated that mucosal metabolites did not differ in different parts of the colon in either the IBS-D or HC groups. (2) In the mucosal microbiome analyses, no differences between the microbiota of the two parts of the colon were found by using Principal Co-ordinates Analysis (PCoA). In IBS group, comparing with sigmoid mucosa, the chao1 richness indice was higher and the Shannon index was lower in the ileocecal mucosa (p = 0.40, p = 0.22). However, in the HC group, microbiome analysis of the ileocecal mucosa showed lower values for Chao 1 and Shannon indices than those of the sigmoid colon mucosa (p = 0.06, p = 0.86). (3) Compared with the HC group, 1,113 metabolic signal peaks were upregulated, whereas 594 metabolites were downregulated in the IBS-D samples. Moreover, the PCA of the metabolites showed significant separation between the IBS-D and HC groups. (4) Chao1 expression was significantly higher in the mucosal microbiota with IBS-D than in the HC (p = 0.03). The Shannon index was lower in IBS-D, but the difference was not statistically significant (p = 0.53). PCoA revealed a significant difference in the microflora structure between the IBS-D and HC groups. Conclusion: The mucosal metabolic profile and mucosal flora structure of the colon were similar, despite different locations in IBS and healthy subjects. IBS had abnormal colonic mucosal metabolism and flora disturbances.
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BACKGROUND: Neuropsychiatric disorders are highly heritable and have overlapping genetic underpinnings. Single nucleotide polymorphisms (SNPs) in the gene CACNA1C have been associated with several neuropsychiatric disorders, across multiple genome-wide association studies. METHOD: A total of 70,711 subjects from 37 independent cohorts with 13 different neuropsychiatric disorders were meta-analyzed to identify overlap of disorder-associated SNPs within CACNA1C. The differential expression of CACNA1C mRNA in five independent postmortem brain cohorts was examined. Finally, the associations of disease-sharing risk alleles with total intracranial volume (ICV), gray matter volumes (GMVs) of subcortical structures, cortical surface area (SA), and average cortical thickness (TH) were tested. RESULTS: Eighteen SNPs within CACNA1C were nominally associated with more than one neuropsychiatric disorder (P < .05); the associations shared among schizophrenia, bipolar disorder, and alcohol use disorder survived false discovery rate correction (five SNPs with P < 7.3 × 10-4 and q < 0.05). CACNA1C mRNA was differentially expressed in brains from individuals with schizophrenia, bipolar disorder, and Parkinson's disease, relative to controls (three SNPs with P < .01). Risk alleles shared by schizophrenia, bipolar disorder, substance dependence, and Parkinson's disease were significantly associated with ICV, GMVs, SA, or TH (one SNP with P ≤ 7.1 × 10-3 and q < 0.05). CONCLUSION: Integrating multiple levels of analyses, we identified CACNA1C variants associated with multiple psychiatric disorders, and schizophrenia and bipolar disorder were most strongly implicated. CACNA1C variants may contribute to shared risk and pathophysiology in these conditions.
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Trouble bipolaire , Canaux calciques de type L , Maladie de Parkinson , Schizophrénie , Humains , Canaux calciques de type L/génétique , Prédisposition génétique à une maladie , Étude d'association pangénomique , Maladie de Parkinson/génétique , Polymorphisme de nucléotide simple/génétique , ARN messager , Schizophrénie/génétique , Trouble bipolaire/génétiqueRÉSUMÉ
Yucca schidigera extract (YSE) is a green feed additive that is known to reduce toxic gas emissions and promote intestinal health in animal production. This study investigated the potential of dietary YSE supplementation to mitigate the negative effect of Clostridium perfringens and coccidia infection on productive performance and gut health in laying hens. A total of 48 Lohmann gray laying hens (35 wk of age) were randomly allotted to 1 of 2 groups (n = 24) fed with either a basal diet or a YSE-supplemented diet for 45 d. From d 36 to 45, half of the hens in each group were orally administrated with Clostridium perfringens type A and coccidia. This challenge impaired productive performance and egg quality (P < 0.05), destroyed jejunal morphology and functions (P < 0.05), induced jejunal epithelial cell apoptosis (P < 0.05), and downregulated the antioxidant capacity and Nrf2 pathway expression of jejunal mucosa (P < 0.05) in laying hens. Supplementing YSE in the laying hen diet, to some extents, improved productive performance and egg quality (P < 0.05), and alleviated the effect of challenge on morphology, functions, cell apoptosis, and antioxidant capacity in the jejunum (P < 0.05). Overall, the results suggested that dietary YSE supplementation might mitigate the negative effects of Clostridium perfringens and coccidia infection on gut health, and thereby improve the productive performance and egg quality of laying hens, possibly through enhancing the antioxidant capacity of the jejunum.
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Antioxydants , Yucca , Animaux , Femelle , Aliment pour animaux/analyse , Antioxydants/métabolisme , Poulets/physiologie , Clostridium perfringens , Régime alimentaire/médecine vétérinaire , Compléments alimentairesRÉSUMÉ
Ring Finger Protein 113 (RNF113A), an ubiquitin E3 ligase, is genetically associated with many biological processes, including proliferation, differentiation, cell death, and neurogenesis. Recently, RNF113A has been found to be an abnormal expression in many diseases, such as X-linked trichothiodystrophy syndrome and esophageal cancer. Here, we explore the potential mechanism of RNF113A in the progression of cervical cancer (CC). In this study, we evaluated the expression level and biological function of RNF113A in CC both in vitro and in vivo by bioinformatic prediction, DIA proteomic analysis, compensation experiment, Co-IP, dual-luciferase reporter assay and nude mouse xenograft to identify the RNF113A-associated autophagy pathways involved with tumorigenesis. Consistent with the prediction from biological information analysis, we found that RNF113A was highly expressed in human CC tissues and cells. In addition, this study illustrated that the high expression of RNF113A dramatically promoted proliferation and suppressed autophagy both in vitro and in vivo. In contrast, low expression of RNF113A enhanced autophagy activities and inhibited tumor growth in CC. We also found that miRNA-197, the level of which (negative correlation with RNF113A) declined in human CC, directly restrained the expression of RNF113A. Mechanistically, proteomic and mechanistic assays uncovered that RNF113A confirmed as the direct downstream target of miR-197, promoted proliferation and restrained autophagy in CC not through direct ubiquitination degradation of autophagy marker Beclin1 but via CXCR4/CXCL12/AKT/ERK/Beclin1 signal transduction axis. In summary, we found a new miR-197/RNF113 A/CXCR4/CXCL12/AKT/ERK/Beclin1 regulation pathway that plays an important part in the survival and progression of CC.
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microARN , Tumeurs du col de l'utérus , Animaux , Femelle , Humains , Souris , Autophagie/génétique , Bécline-1/génétique , Bécline-1/métabolisme , Lignée cellulaire tumorale , Prolifération cellulaire/génétique , Chimiokine CXCL12/métabolisme , Protéines de liaison à l'ADN/métabolisme , Régulation de l'expression des gènes tumoraux , microARN/génétique , microARN/métabolisme , Protéomique , Protéines proto-oncogènes c-akt/génétique , Protéines proto-oncogènes c-akt/métabolisme , Transduction du signal/physiologie , Tumeurs du col de l'utérus/anatomopathologieRÉSUMÉ
Tropomyosin (TM) is a major allergen in crustaceans, and its allergenicity mainly depends on epitopes. In this study, the locations of IgE-binding sites between plasma active particles and allergenic peptides of TM in shrimp (Penaeus chinensis) during cold plasma (CP) treatment were explored. Results showed that the IgE-binding ability of two critical peptides (P1 and P2) increased and then decreased by 9.97 % and 19.50 % after 15 min of CP treatment. It was the first time to show that the contribution rate of target active particles was â¢O > e(aq)- > â¢OH for reducing IgE-binding ability by 23.51 %-45.40 %, and the contribution rates of other long-lived particles including NO3- and NO2- was about 54.60 %-76.49 %. In addition, Glu131 and Arg133 in P1 and Arg255 in P2 were certified as the IgE sites. These results were helpful for accurately controlling TM allergenicity, shedding more light on allergenicity mitigation during food processing.
Sujet(s)
Penaeidae , Gaz plasmas , Animaux , Tropomyosine/composition chimique , Penaeidae/composition chimique , Séquence d'acides aminés , Allergènes/composition chimique , Peptides , Sites de fixation , Immunoglobuline ERÉSUMÉ
BACKGROUND: Pigmented prurigo (PP) is a chronic and recurrent inflammatory skin disease. PP is not common clinically, but it is easily misdiagnosed because of its diversified clinical manifestations in different stages. MATERIALS AND METHODS: We retrospectively analyzed the clinical, histopathological, dermoscopy, and reflectance confocal microscopy (RCM) features of 20 patients diagnosed as PP. RESULTS: The female predominance ratio was revealed with male to female of 1:4. Seven female patients were on a diet (without staple food) and one patient had a history of diabetes. Eight cases were suffered in spring, six cases in winter, three cases in summer, and three cases in autumn. Multiple sites were involved in 13 cases. Four patients had urticarial papules and plaques. Nineteen patients had erythematous papules with reticular distribution, of which 14 cases accompanied reticulate hyperpigmentation, four cases with papulovesicle, and two cases accompanied with pustules. One patient only showed reticulate hyperpigmentation. In the early lesions, dermatoscopy showed pink oval lesions, punctate or linear vessels, and pale yellow rings around the skin lesions. RCM is characterized by spongiosis, spongy vesicle, neutrophils scattered in the epidermis, which was consistent with epidermis spongiosis, neutrophils infiltrating into the upper epidermis and necrotic keratinocytes in histopathology. In the fully developed lesions, dermatoscopy showed pink lesions with brown pigment granules in the center and linear vessels in the edge. RCM showed that demarcation of epidermis and dermis is not clear, and inflammatory cells can be seen in the upper dermis and histopathologically lesions assumed a patchy lichenoid pattern, and the inflammatory cells infiltrating the dermis were dominated by lymphocytes. In the late lesions, dermatoscopy showed grainy grayish-brown or yellowish-brown pigmentation surrounding the hair follicle merging with each other. RCM showed that pigment granules were increased on the ring of basal cells, inflammatory cells were sparsely infiltrated in the dermal papilla and superficial layer, and epidermis slightly hyperplastic, with melanophages and a few lymphocytes infiltrating the superficial dermis in histopathology. CONCLUSION: PP is easily misdiagnosed and not always occurs in those on a restrictive diet. A combination of dermatoscopy and RCM is helpful for its diagnosis of PP.