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Hepatitis C virus (HCV) represents a formidable menace to human health, necessitating urgent attention. The objective of this study was to assess the efficacy and safety of HCV health management in the city of Guigang which consists of five districts, employing a comprehensive multi-modal approach. The study systematically carried out HCV screening in Guigang city which consists of five districts, such as Gangbei District, Gangnan District, Guiping District, Qintang District, and Pingnan District from 1 January 2016 to 30 December 2022. The target population consisted of individuals residing in these aforementioned districts, falling within the age range of 30-75 years. A multidisciplinary HCV management team was established to deliver anti-HCV screening, diagnosis, and direct-acting antiviral (DAA) therapy. The primary outcome of interest was the achievement of sustained virologic response (SVR). A total of 2489 individuals were included as the target population, with 1694 individuals residing in Gangbei District, 202 in Gangnan District, 111 in Qintang District, 167 in Pingnan District, and 315 in Guiping District. Out of these individuals, 2478 were subjected to anti-HCV screening. The screening rates varied across the districts, ranging from a peak of 99.55% in Guigang City to a nadir of 98.41% in Guiping District. Remarkably, within Guigang City, a noteworthy enhancement was observed in the HCV-RNA diagnosis rate from 23.4% prior to program implementation to a remarkable 100% following 7 years of intervention and management. Furthermore, the diagnosis and treatment coordination rate experienced a substantial improvement, rising from 26.8% before program inception to 80%. Importantly, a total of 1180 individuals affected by hepatitis C were successfully cured, equating to a 100% cure rate. Logistic regression analysis revealed a significant association between serological status and factors such as Aging, bilirubin, and glutamic oxalacetic transaminase. The findings from our investigation unveil a pioneering HCV management model, exemplified by the Guigang model, which has contributed crucially to HCV microclearance efforts and serves as an invaluable reference for future initiatives.
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Hepatite C Crônica , Hepatite C , Telemedicina , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/epidemiologia , Antivirais/uso terapêutico , Hepatite C/diagnóstico , Hepatite C/tratamento farmacológico , Hepatite C/epidemiologia , Hepacivirus/genética , Resposta Viral SustentadaRESUMO
With the development of high-throughput DNA sequencing and molecular analysis technologies, next-generation probiotics (NGPs) are increasingly gaining attention as live bacterial therapeutics for treatment of diseases. However, compared to traditional probiotics, NGPs are much more vulnerable to the harsh conditions in the human gastrointestinal tract, and their functional mechanisms in the gut are more complex. Prebiotics have been confirmed to play a critical role in improving the function and viability of traditional probiotics. Defined as substrates that are selectively utilized by host microorganisms conferring a health benefit, prebiotics are also important for NGPs. This review summarizes potential prebiotics for use with NGPs and clarifies their characteristics and functional mechanisms. Then we particularly focus on illustrating the protective effects of various prebiotics by enhancing the antioxidant capacity and their resistance to digestive fluids. We also elucidate the role of prebiotics in regulating anti-bacterial effects, intestinal barrier maintenance, and cross-feeding mechanisms of NPGs. With the expanding range of candidate NGPs and prebiotic substrates, more studies need to be conducted to comprehensively elucidate the interactions between prebiotics and NGPs outside and inside hosts, in order to boost their nutritional and healthcare applications.
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Microbioma Gastrointestinal , Probióticos , Humanos , Prebióticos , Probióticos/farmacologia , Trato Gastrointestinal/microbiologia , DisbioseRESUMO
The depletion of Bacteroides in the gut is closely correlated with the progression of alcoholic liver disease (ALD). This study aimed to identify Bacteroides strains with protective effects against ALD and evaluate the synergistic effects of Bacteroides and pectin in this disease. Mice were fed Lieber-DeCarli alcohol diet to establish an experimental ALD model and pre-treated with 4 Bacteroides strains. The severity of the liver injury, hepatic steatosis, and inflammation was evaluated through histological and biochemical assays. We found that Bacteroides fragilis ATCC25285 had the best protective effects against ALD strains by alleviating both ethanol-induced liver injury and steatosis. B. fragilis ATCC25285 could counteract inflammatory reactions in ALD by producing short-chain fat acids (SCFAs) and enhancing the intestinal barrier. In the subsequent experiment, the synbiotic combination of B. fragilis ATCC25285 and pectin was evaluated and the underlying mechanisms were investigated by metabolomic and microbiome analyses. The combination elicited superior anti-ALD effects than the individual agents used alone. The synergistic effects of B. fragilis ATCC25285 and pectin were driven by modulating gut microbiota, improving tryptophan metabolism, and regulating intestinal immune function. Based on our findings, the combination of B. fragilis ATCC25285 and pectin can be considered a potential treatment for ALD. KEY POINTS: ⢠B. fragilis ATCC25285 was identified as a protective Bacteroides strain against ALD. ⢠The synbiotic combination of B. fragilis and pectin has better anti-ALD effects. ⢠The synbiotic combination modulates gut microbiota and tryptophan metabolism.
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Bacteroides , Hepatopatias Alcoólicas , Animais , Etanol/metabolismo , Inflamação/metabolismo , Fígado/metabolismo , Hepatopatias Alcoólicas/patologia , Hepatopatias Alcoólicas/prevenção & controle , Camundongos , Camundongos Endogâmicos C57BL , Pectinas/metabolismo , Triptofano/metabolismoRESUMO
The gut microbiota plays an important role in colorectal cancer (CRC), and the use of probiotics might be a promising intervention method. The aim of our study was to investigate the beneficial effect of Bifidobacterium bifidum CGMCC 15068 on an azoxymethane (AOM)/dextran sulphate sodium (DSS)-induced colitis-associated CRC (CAC) mouse model. CAC was induced by an intra-peritoneal injection of AOM (10 mg/kg) and three 7-day cycles of 2% DSS in drinking water with a 14-day recovery period between two consecutive DSS administrations. B. bifidum CGMCC 15068 (3 × 109 CFU/mL) was gavaged once daily during the recovery period. Then, the faecal microbial composition and metabolome were profiled using the 16S rRNA sequencing technology and gas chromatography-mass spectrometry (GC-MS), respectively. The administration of B. bifidum CGMCC 15068 attenuated tumourigenesis in the CAC mouse model. In addition, B. bifidum CGMCC 15068 pre-treatment increased the relative abundance of Akkermansia, Desulfovibrionaceae, Romboutsia, Turicibacter, Verrucomicrobiaceae, Ruminococcaceae_UCG_013, Lachnospiraceae_UCG_004, and Lactobacillus. Meanwhile, B. bifidum CGMCC 15068 altered metabolites involved in the citrate cycle (TCA cycle), glycolysis, butyrate metabolism, fatty acid biosynthesis, and galactose metabolism. Several significant correlations were identified between the differentially abundant microbes and metabolites. These findings supported the beneficial role of B. bifidum CGMCC 15068 in intestinal health by modulating dysbiosis and the gut metabolic profile. The manipulation of the gut microbial composition using probiotics might be a promising prevention strategy for CRC. Long-term and large-scale clinical trials are warranted for the potential clinical applications of this strategy in the future.
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Bifidobacterium bifidum/fisiologia , Neoplasias Associadas a Colite/tratamento farmacológico , Microbioma Gastrointestinal/efeitos dos fármacos , Metaboloma/efeitos dos fármacos , Probióticos/administração & dosagem , Animais , Azoximetano/toxicidade , Carcinogênese/efeitos dos fármacos , Neoplasias Associadas a Colite/induzido quimicamente , Neoplasias Associadas a Colite/patologia , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Fezes/química , Fezes/microbiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Probióticos/farmacologiaRESUMO
BACKGROUND The suicide risk of patients with cancer is higher than the general population. Our research aimed to explore the Surveillance, Epidemiology, and End Results (SEER) database to define incidence and quest risk factors for death of suicide in patients with Kaposi's sarcoma (KS) in the United States (US). MATERIAL AND METHODS We screened KS patients without human immunodeficiency virus status in the SEER database from 1980 to 2016, calculated the standardized mortality ratios of them by comparing the rates with those of the US general population from 1980 to 2016, and identified relevant suicide risk factors by univariable and multivariable logistic regression analyses. RESULTS The suicide rates of KS patients and US general population were 115.31 (110 suicides among 21 405 patients) and 15.1 per 100 000 person-years, respectively, thus the standardized mortality ratio was 7.64 (95% confidence interval [CI], 6.28-9.21). The multivariate analysis showed that black race (versus white race, hazard ratio [HR]: 0.43, 95% CI: 0.21-0.89, P=0.022), advanced age at diagnosis (≥55 years versus 18-44 years, HR: 0.31, 95% CI: 0.14-0.66, P=0.002), and chemotherapy (versus no chemotherapy, HR: 0.60, 95% CI: 0.37-0.96, P=0.032) were protective factors for suicide among KS patients. CONCLUSIONS Clinicians and caregivers can apply our findings to identify KS patients with high suicide risk characteristics (white race, age of 18-44 years, non-chemotherapy) and exert timely interventions during patient diagnosis, treatment, and follow-up to reduce the suicide rate in this population.
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Sarcoma de Kaposi/psicologia , Suicídio , Adolescente , Adulto , Fatores Etários , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Programa de SEER , Sarcoma de Kaposi/tratamento farmacológico , Estados Unidos , População Branca , Adulto JovemRESUMO
The liver is an important digestive gland, and acute liver failure results in high mortality. Probiotics are considered potential adjuvant therapies for liver disease. This study aimed to investigate the beneficial effects of Lactobacillus helveticus R0052 on acute liver injury and the underlying mechanisms. Sprague-Dawley rats were gavaged with L. helveticus R0052 suspensions (3 × 109 CFU) for 1 week. Subsequently, acute liver injury was induced by intraperitoneal D-galactosamine injection on the eighth day. After 24 h, samples (blood, liver, ileum, faeces) were collected and assessed for histological injury, inflammation, intestinal barrier, gut microbiome and metabolome. L. helveticus R0052 alleviated aminotransferase, bilirubin and total bile acid elevation and histological hepatic injuries. Additionally, L. helveticus R0052 exhibited anti-inflammatory properties by downregulating Toll-like receptors, tumour necrosis factor-α and nuclear factor-κb transcription in liver samples and decreasing proinflammatory cytokine plasma concentrations. Additionally, L. helveticus R0052 ameliorated intestinal abnormalities and regulated Toll-like receptors, claudin2 and mucin3 gene transcription in the intestine. These effects were associated with gut microbiome and metabolome modulation by L. helveticus R0052. Probiotic pretreatment enriched Lactobacillus and Bacteroides and depleted Flavonifractor and Acetatifactor in the gut microbiome. Meanwhile, L. helveticus R0052 improved carbohydrate and fatty acid metabolism and reduced lithocholic acid levels. These results indicate that L. helveticus R0052 is promising for alleviating acute liver injury and provide new insights regarding the correlations among the microbiome, the metabolome, the intestinal barrier and liver disease.
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Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Galactosamina/toxicidade , Microbioma Gastrointestinal/efeitos dos fármacos , Lactobacillus helveticus/fisiologia , Metaboloma/efeitos dos fármacos , Probióticos/uso terapêutico , Animais , Biomarcadores/sangue , Doença Hepática Induzida por Substâncias e Drogas/patologia , Citocinas/sangue , Fezes/química , Fezes/microbiologia , Galactosamina/administração & dosagem , Intestinos/efeitos dos fármacos , Intestinos/microbiologia , Intestinos/patologia , Fígado/efeitos dos fármacos , Fígado/patologia , Fígado/fisiopatologia , Masculino , Probióticos/administração & dosagem , Probióticos/farmacologia , Ratos , Ratos Sprague-DawleyRESUMO
The aim of this study was to elucidate the reproductive toxicity of the coadministration of diltiazem and cyclosporine A or tacrolimus. Testicular development, semen quality, sex hormones and testicular tissues were assessed in unilateral nephrectomised (UN) rats, including the control group, UN group, UN+CsA group, UN+FK506 group, UN+Rapa group, UN+CsA+Dil group and UN+FK506+Dil group. The testicular coefficient, the sperm number and the sperm motility were lower in the treatment groups (except UN+FK506) than in the control and UN groups (all p < 0.05). The lowest sperm number and motility were identified in the UN+CsA+Dil group, followed by the UN+CsA group. The proportion of abnormal sperm was higher in the UN+CsA and UN+CsA+Dil groups than in the control and UN groups, respectively (p < 0.05). The plasma concentrations of sex hormones were changed in the treatment groups. Dil can increase the blood concentrations of CsA and FK506 (âp < 0.05, âp < 0.05). Therapeutic doses of these agents induced morphological changes in the testicular tissue and ultrastructural changes in the testosterone, mesenchymal cells and supporting cells. Our present study suggests that Dil can increase the testicular toxicity of CNIs (calcineurin inhibitors, including CsA and FK506) by enhancing the plasma concentrations of CNIs.
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Inibidores de Calcineurina/toxicidade , Bloqueadores dos Canais de Cálcio/toxicidade , Ciclosporina/toxicidade , Diltiazem/toxicidade , Imunossupressores/toxicidade , Tacrolimo/toxicidade , Animais , Modelos Animais de Doenças , Sinergismo Farmacológico , Quimioterapia Combinada/efeitos adversos , Hormônios Esteroides Gonadais/sangue , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Humanos , Rim/cirurgia , Transplante de Rim/efeitos adversos , Masculino , Microscopia Eletrônica de Transmissão , Nefrectomia , Ratos , Ratos Sprague-Dawley , Análise do Sêmen , Motilidade dos Espermatozoides/efeitos dos fármacos , Testículo/efeitos dos fármacos , Testículo/patologia , Testículo/ultraestruturaRESUMO
In order to get high-resolution glomerulus image with large field of view(FOV),stitching multiple small FOV images with high-resolution is necessary.Directly stitching images without properly correction is not acceptable and cannot afford any significant assistance in pathological diagnosis for intensity inhomogeneity and geometric distortion.Therefore we proposed a method of distortion correction and intensity inhomogeneity correction of glomerulus transmission electron microscope(TEM)image.In this paper,we firstly describe how these two distortions degrade images.Secondly,based on the TEM imaging system,image acquisition model and distortion correction model were proposed.Then according to these two models,distortions were greatly degraded and stitching results were improved by respectively applying two corrections,intensity inhomogeneity correction and geometric distortion correction.With the method proposed here,the result was improved significantly and stripes,fuzzy and artifacts were decreased dramatically.Our method has been proved to be valid to solve the problems of TEM glomerulus image distortion and at the same time to improve the result of multiple TEM glomerulus image stitching.
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Processamento de Imagem Assistida por Computador , Glomérulos Renais/diagnóstico por imagem , Microscopia Eletrônica de Transmissão , Algoritmos , Artefatos , HumanosRESUMO
Functional and pathological recovery after spinal cord injury (SCI) is often incomplete due to the limited regenerative capacity of the central nervous system (CNS), which is further impaired by several mechanisms that sustain tissue damage. Among these, the chronic activation of immune cells can cause a persistent state of local CNS inflammation and damage. However, the mechanisms that sustain this persistent maladaptive immune response in SCI have not been fully clarified yet. In this study, we integrated histological analyses with proteomic, lipidomic, transcriptomic, and epitranscriptomic approaches to study the pathological and molecular alterations that develop in a mouse model of cervical spinal cord hemicontusion. We found significant pathological alterations of the lesion rim with myelin damage and axonal loss that persisted throughout the late chronic phase of SCI. This was coupled by a progressive lipid accumulation in myeloid cells, including resident microglia and infiltrating monocyte-derived macrophages. At tissue level, we found significant changes of proteins indicative of glycolytic, tricarboxylic acid cycle (TCA), and fatty acid metabolic pathways with an accumulation of triacylglycerides with C16:0 fatty acyl chains in chronic SCI. Following transcriptomic, proteomic, and epitranscriptomic studies identified an increase of cholesterol and m6A methylation in lipid-droplet-accumulating myeloid cells as a core feature of chronic SCI. By characterizing the multiple metabolic pathways altered in SCI, our work highlights a key role of lipid metabolism in the chronic response of the immune and central nervous system to damage.
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Automatic segmentation of the three substructures of glomerular filtration barrier (GFB) in transmission electron microscopy (TEM) images holds immense potential for aiding pathologists in renal disease diagnosis. However, the labor-intensive nature of manual annotations limits the training data for a fully-supervised deep learning model. Addressing this, our study harnesses self-supervised representation learning (SSRL) to utilize vast unlabeled data and mitigate annotation scarcity. Our innovation, GCLR, is a hybrid pixel-level pretext task tailored for GFB segmentation, integrating two subtasks: global clustering (GC) and local restoration (LR). GC captures the overall GFB by learning global context representations, while LR refines three substructures by learning local detail representations. Experiments on 18,928 unlabeled glomerular TEM images for self-supervised pre-training and 311 labeled ones for fine-tuning demonstrate that our proposed GCLR obtains the state-of-the-art segmentation results for all three substructures of GFB with the Dice similarity coefficient of 86.56 ± 0.16%, 75.56 ± 0.36%, and 79.41 ± 0.16%, respectively, compared with other representative self-supervised pretext tasks. Our proposed GCLR also outperforms the fully-supervised pre-training methods based on the three large-scale public datasets - MitoEM, COCO, and ImageNet - with less training data and time.
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Barreira de Filtração Glomerular , Glomérulos Renais , Análise por Conglomerados , Microscopia Eletrônica de Transmissão , Aprendizado de Máquina Supervisionado , Processamento de Imagem Assistida por ComputadorRESUMO
Primary sclerosing cholangitis (PSC), a rare chronic cholestatic liver disease, is characterized by intrahepatic or extrahepatic strictures accompanied by biliary fibrosis. So far, there are no effective therapies to slow down the progression of this disease. Farnesoid X receptors (FXRs) are ligand-activated transcription factors involved in the control of bile acid (BA) synthesis and enterohepatic circulation. Therefore, targeting FXRs holds promise as a potential approach for treating PSC. Pediococcus pentosaceus Li05 is a probiotic that was isolated from healthy volunteers and has previously been shown to have an anti-inflammatory effect in DSS-induced colitis. In this study, we established a 3,5-diethoxycarbonyl-1,4-Dihydrocollidine (DDC)-induced cholestasis mouse model and investigated the effects of Pediococcus pentosaceus Li05 on PSC. Our findings revealed that administration of Li05 significantly attenuated liver damage, hepatic inflammation, and fibrosis, as well as bile duct hyperplasia. Li05 activated the hepatic FXR-SHP and ileal FXR-FGF15 signaling pathways to decrease the expression of Cyp7a1. In addition, the Li05-modulated gut microbiota structure especially improved the abundance of 7α-dehydroxylation bacteria like Eubacterium. The intervention of Li05 also improved the intestinal barrier and reduced bacterial endotoxin translocation. Based on these findings, Li05 shows promise for future application as a therapeutic strategy for cholestasis.
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Colestase , Probióticos , Camundongos , Animais , Humanos , Pediococcus pentosaceus , Ácidos e Sais Biliares/metabolismo , Colestase/tratamento farmacológico , Colestase/patologia , Fígado/metabolismo , Endotoxinas/metabolismo , FibroseRESUMO
The presence of exopolysaccharides (EPS), a type of biomacromolecules, on the surface of probiotics play an important role in mucoadhesion, and it can be severely influenced by environments during gastrointestinal transit. In this study, the impact of gastrointestinal factors on surface properties of two probiotics (Lactobacillus rhamnosus GG and Pediococcus pentosaceus LI05) was investigated. Probiotic suspensions had relatively high viscosities and exhibited pronounced shear-thinning behavior due to the presence of EPS. The ζ-potential of both probiotics was relatively low and was not believed to play an important role in mucoadhesion. Compared to the control, the adhesive forces tended to decrease in the presence of gastric acids but increase in the presence of bile salts, since bile salts led to a thicker more open EPS layer compared to gastric acids. Although the functional groups of EPS in both probiotics are similar according to the study by FT-IR spectroscopy, the molecular weight of purified EPS in LI05 was much higher, ranging from 10,112 Da to 477,763 Da, which may contribute to higher rupture length in LI05 group. These results suggest that probiotic-mucin interactions are governed by the compositions and changes in the EPS of the probiotics in different gastrointestinal conditions, which contribute to a better understanding of the mucoadhesive behavior of the probiotics in the GIT.
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Currently approved therapeutical strategies for inflammatory bowel diseases (IBD) suffer from variable efficacy and association with risk of serious side effects. Therefore, efforts have been made in searching for alternative therapeutics strategies utilizing gut microbiota manipulation. In this study, we show that the probiotic strain Ligilactobacillus salivarius Li01 (Li01) and the phytochemical prebiotic resveratrol (RSV) have synergistic effect in ameliorating colitis in mice. Oral coadministration of Li01 (109 CFU/d) and RSV (1.5 g/kg/d) promoted restoration of various inflammatory injuries and gut microbiota composition, exhibiting a favorable anti-inflammatory effect in DSS-induced colitis mice. The combination treatment was associated with reductions in the levels of proinflammatory cytokines IL-1ß and IL-6 and increases in the levels of the anti-inflammatory cytokine IL-17A in mouse serum. Moreover, the combination treatment was found to alter the composition and metabolism of the gut microbiota, especially influencing the production of short chain fatty acids and anti-inflammatory related molecules. The mechanism underlying the improved anti-inflammatory effect from the RSV and Li01 combination treatment was found to be associated with the environmental sensor mammalian aryl hydrocarbon receptor (AHR) and tryptophan metabolism pathway. Administration of RSV in combination with Li01 in different mouse model led to enhanced conversion of RSV into metabolites, including dihydroresveratrol (DHR), resveratrol-sulfate, and resveratrol-glucuronide. DHR was found to be the dominant metabolite of RSV in conventional and colitis mice. An increased DHR/RSV ratio was confirmed to activate AHR and contribute to an enhanced anti-inflammatory effect. DHR is considered as a potential AHR ligand. The DHR/RSV ratio also affected the serotonin pathway by controlling the expression of Tph1, SERT, and 5-HT7R leading to amelioration of colitis in mice. Our data suggest that treatment with a combination of Li01 and RSV has potential as a therapeutic strategy for IBD; further investigation of this combination in clinical settings is warranted.
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Macrophages and microglia play important roles in chronic neuroinflammation following spinal cord injury (SCI). Although macrophages and microglia have similar functions, their phagocytic and homeostatic abilities differ. It is difficult to distinguish between these two populations in vivo, but single-cell analysis can improve our understanding of their identity and heterogeneity. We conducted bioinformatics analysis of the single-cell RNA sequencing dataset GSE159638, identifying apolipoprotein E (APOE) as a hub gene in both macrophages and microglia in the subacute and chronic phases of SCI. We then validated these transcriptomic changes in a mouse model of cervical spinal cord hemi-contusion and observed myelin uptake, lipid droplets, and lysosome accumulation in macrophages and microglia following SCI. Finally, we observed that knocking out APOE aggravated neurological dysfunction, increased neuroinflammation, and exacerbated the loss of white matter. Targeting APOE and the related cholesterol efflux represents a promising strategy for reducing neuroinflammation and promoting recovery following SCI.
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Apolipoproteínas E , Macrófagos , Microglia , Doenças Neuroinflamatórias , Traumatismos da Medula Espinal , Animais , Apolipoproteínas E/genética , Apolipoproteínas E/imunologia , Biologia Computacional , Macrófagos/imunologia , Camundongos , Microglia/imunologia , Doenças Neuroinflamatórias/genética , Doenças Neuroinflamatórias/imunologia , Traumatismos da Medula Espinal/genética , Traumatismos da Medula Espinal/imunologiaRESUMO
Antibiotic treatment is often followed by Clostridium difficile infection (CDI), which causes severe diarrhea and other health issues. Oral administration of Pediococcus pentosaceus Li05 (Li05) has been shown to have great potential in preventing CDI. However, the viability of Li05 is greatly reduced during storage and passage through the gastrointestinal (GI) tract, which limits its biological activity. In this study, a gastro-responsive microgel was designed to encapsulate and protect Li05 to enhance its efficacy against CDI. The viability of Li05 encapsulated within the microgels was significantly enhanced during long-term storage and after exposure to simulated GI fluids. Moreover, this gastro-responsive microgel led to greater sustained release of the probiotic. In a mouse CDI model, we found that encapsulated Li05 was better at inhibiting C. difficile infection than nonencapsulated Li05, as demonstrated through analysis of the probiotic survival rate, spleen weight, colonic histology, and inflammatory cytokine levels. Moreover, the gut microbial diversity was enriched by treatment with encapsulated Li05. These results suggest that encapsulating Li05 within biopolymer microgels may enhance its ability to prevent and treat CDI using functional foods, supplements, or pharmaceuticals.
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Infecções por Clostridium/tratamento farmacológico , Diarreia/prevenção & controle , Microgéis/química , Pediococcus pentosaceus , Probióticos/administração & dosagem , Animais , Antibacterianos/efeitos adversos , Diarreia/induzido quimicamente , Modelos Animais de Doenças , Composição de Medicamentos , Armazenamento de Medicamentos , Feminino , Camundongos , Camundongos Endogâmicos C57BLRESUMO
The low viability during gastrointestinal transit and poor mucoadhesion considerably limits the effectiveness of Ligilactobacillus salivarius Li01 (Li01) in regulating gut microbiota and alleviating inflammatory bowel disease (IBD). In this study, a delivery system was designed through layer-by-layer (LbL) encapsulating a single Li01cell with chitosan and alginate. The layers were strengthened by cross-linking to form a firm and mucoadhesive shell (~10 nm thickness) covering the bacterial cell. The LbL Li01 displayed improved viability under simulated gastrointestinal conditions and mucoadhesive function. Almost no cells could be detected among the free Li01 after 2 h incubation in digestive fluids, while for LbL Li01, the total reduction was around 3 log CFU/mL and the viable number of cells remained above 6 log CFU/mL. Besides, a 5-fold increase in the value of rupture length and a two-fold increase in the number of peaks were found in the (bacteria-mucin) adhesion curves of LbL Li01, compared to those of free Li01. Oral administration with LbL Li01 on colitis mice facilitated intestinal barrier recovery and restoration of the gut microbiota. The improved functionality of Li01 by LbL encapsulation could increase the potential for the probiotic to be used in clinical applications to treat IBD; this should be explored in future studies.
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Técnicas Bacteriológicas , Lactobacillus/fisiologia , Animais , Aderência Bacteriana , Biomarcadores , Linhagem Celular , Colite/etiologia , Colite/metabolismo , Colite/patologia , Citocinas/metabolismo , Modelos Animais de Doenças , Suscetibilidade a Doenças , Humanos , Mediadores da Inflamação , Doenças Inflamatórias Intestinais/etiologia , Doenças Inflamatórias Intestinais/metabolismo , Camundongos , Viabilidade Microbiana , Probióticos/administração & dosagemRESUMO
Orally administered probiotics encounter various challenges on their journey through the mouth, stomach, intestine and colon. The health benefits of probiotics are diminished mainly due to the substantial reduction of viable probiotic bacteria under the harsh conditions in the gastrointestinal tract and the colonization resistance caused by commensal bacteria. In this review, we illustrate the factors affecting probiotic viability and their mucoadhesive properties through their journey in the gastrointestinal tract, including a discussion on various mucosadhesion-related proteins on the probiotic cell surface which facilitate colonization.
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Probióticos , Administração Oral , Trato Gastrointestinal , Trânsito Gastrointestinal , IntestinosRESUMO
Aim: Investigation of characteristics of different duodenal microbial colonization states in patients with liver cirrhosis (LC). Materials & methods: Deep-sequencing analyses of the 16S rRNA gene V1-V3 regions were performed. Results: Both bacterial compositions and richness were different between the three-clustered LC microbiotas, in other words, Cluster_1_LC, Cluster_2_LC and Cluster_3_LC. Cluster_1_LC were more likely at severe dysbiosis status due to its lowest modified cirrhosis dysbiosis ratio. OTU12_Prevotella and OTU10_Comamonas were most associated with Cluster_1_LC and Cluster_3_LC, respectively, while OTU38_Alloprevotella was vital in Cluster_2_LC. Pyruvate-ferredoxin/flavodoxin oxidoreductase, dihydroorotate dehydrogenase and branched-chain amino acid transport system substrate-binding protein were most associated with Cluster_1_LC, Cluster_2_LC and Cluster_3_LC, respectively. Conclusion: The three duodenal microbial colonization states had distinct representative characteristics, which might reflect the health status of cirrhotic patients.
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Duodeno/microbiologia , Microbioma Gastrointestinal , Cirrose Hepática/microbiologia , Bactérias/genética , Disbiose , Microbioma Gastrointestinal/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Microbiota , RNA Ribossômico 16S/genéticaRESUMO
The dysbiosis of oropharyngeal (OP) microbiota is associated with multiple diseases, including H7N9 infection. Different OP microbial colonization states may reflect different severities or stages of disease and affect the effectiveness of the treatments. Current study aims to determine the vital bacteria that could possibly drive the OP microbiota in the H7N9 patients to more severe microbial dysbiosis state. The OP microbiotas of 42 H7N9 patients and 30 healthy subjects were analyzed by a series of bioinformatics and statistical analyses. Two clusters of OP microbiotas in H7N9 patients, i.e., Cluster_1_Diseased and Cluster_2_Diseased, were determined at two microbial colonization states by Partition Around Medoids (PAM) clustering analysis, each characterized by distinct operational taxonomic units (OTUs) and functional metabolites. Cluster_1_Diseased was determined at more severe dysbiosis status compared with Cluster_2_Diseased, while OTU143_Capnocytophaga and OTU269_Treponema acted as gatekeepers for both of the two clustered microbiotas. Nine OTUs assigned to seven taxa, i.e., Alloprevotella, Atopobium, Megasphaera, Oribacterium, Prevotella, Stomatobaculum, and Veillonella, were associated with both H7N9 patients with and without secondary bacterial lung infection in Cluster_1. In addition, two groups of healthy cohorts may have potential different susceptibilities to H7N9 infection. These findings suggest that two OP microbial colonization states of H7N9 patients were at different dysbiosis states, which may help determine the health status of H7N9 patients, as well as the susceptibility of healthy subjects to H7N9 infection.
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The gut microbiota is considered a key factor in pathogenesis and progression of inflammatory bowel disease (IBD). The bacterium Pediococcus pentosaceus LI05 alleviated host inflammation by maintaining the gut epithelial integrity, modulating the host immunity, gut microbiota and metabolism, but its effect on IBD remains unclear. The present study aimed to investigate the role and mechanisms of P. pentosaceus LI05. Mice were administered P. pentosaceus LI05 or phosphate-buffered saline once daily by oral gavage for 14 days, and colitis was induced by providing mice 2% DSS-containing drinking water for 7 days. P. pentosaceus LI05 ameliorated colitis in mice and reduced the body weight loss, disease activity index (DAI) scores, colon length shortening, intestinal permeability and the proinflammatory cytokine levels. Furthermore, a significantly altered gut microbiota composition with increased diversity and short-chain fatty acid (SCFA) production was observed in mice treated with P. pentosaceus LI05. Several genera, including Akkermansia and Faecalibacterium, were differentially enriched in the P. pentosaceus LI05-treated mice and were negatively correlated with colitis indices and positively correlated with gut barrier markers and SCFA levels. The P. pentosaceus LI05 treatment alleviated intestinal inflammation by maintaining the intestinal epithelial integrity and modulating the immunological profiles, gut microbiome and metabolite composition. Based on our findings, P. pentosaceus LI05 might be applied as potential preparation to ameliorate colitis.