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1.
Cell ; 182(3): 625-640.e24, 2020 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-32702313

RESUMO

The brain is a site of relative immune privilege. Although CD4 T cells have been reported in the central nervous system, their presence in the healthy brain remains controversial, and their function remains largely unknown. We used a combination of imaging, single cell, and surgical approaches to identify a CD69+ CD4 T cell population in both the mouse and human brain, distinct from circulating CD4 T cells. The brain-resident population was derived through in situ differentiation from activated circulatory cells and was shaped by self-antigen and the peripheral microbiome. Single-cell sequencing revealed that in the absence of murine CD4 T cells, resident microglia remained suspended between the fetal and adult states. This maturation defect resulted in excess immature neuronal synapses and behavioral abnormalities. These results illuminate a role for CD4 T cells in brain development and a potential interconnected dynamic between the evolution of the immunological and neurological systems. VIDEO ABSTRACT.


Assuntos
Encéfalo/citologia , Linfócitos T CD4-Positivos/metabolismo , Feto/citologia , Microglia/citologia , Microglia/metabolismo , Sinapses/metabolismo , Adulto , Animais , Antígenos CD/metabolismo , Antígenos de Diferenciação de Linfócitos T/metabolismo , Escala de Avaliação Comportamental , Células Sanguíneas/citologia , Células Sanguíneas/metabolismo , Encéfalo/embriologia , Encéfalo/metabolismo , Criança , Feminino , Feto/embriologia , Humanos , Lectinas Tipo C/metabolismo , Pulmão/citologia , Pulmão/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pessoa de Meia-Idade , Neurogênese/genética , Parabiose , Células Piramidais/metabolismo , Células Piramidais/fisiologia , Análise de Célula Única , Baço/citologia , Baço/metabolismo , Sinapses/imunologia , Transcriptoma
2.
Gut ; 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38886045

RESUMO

Gastric cancer (GC) is one of the most common malignancies and a prominent cause of cancer mortality worldwide. A distinctive characteristic of GC is its intimate association with commensal microbial community. Although Helicobacter pylori is widely recognised as an inciting factor of the onset of gastric carcinogenesis, increasing evidence has indicated the substantial involvement of microbes that reside in the gastric mucosa during disease progression. In particular, dysregulation in gastric microbiota could play pivotal roles throughout the whole carcinogenic processes, from the development of precancerous lesions to gastric malignancy. Here, current understanding of the gastric microbiota in GC development is summarised. Potential translational and clinical implications of using gastric microbes for GC diagnosis, prognosis and therapeutics are also evaluated, with further discussion on conceptual haziness and limitations at present. Finally, we highlight that modulating microbes is a novel and promising frontier for the prevention and management of GC, which necessitates future in-depth investigations.

3.
Gut ; 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38599786

RESUMO

OBJECTIVE: Probiotic Lactococcus lactis is known to confer health benefits to humans. Here, we aimed to investigate the role of L. lactis in colorectal cancer (CRC). DESIGN: L. lactis abundance was evaluated in patients with CRC (n=489) and healthy individuals (n=536). L. lactis was isolated from healthy human stools with verification by whole genome sequencing. The effect of L. lactis on CRC tumourigenesis was assessed in transgenic Apc Min/+ mice and carcinogen-induced CRC mice. Faecal microbiota was profiled by metagenomic sequencing. Candidate proteins were characterised by nano liquid chromatography-mass spectrometry. Biological function of L. lactis conditioned medium (HkyuLL 10-CM) and functional protein was studied in human CRC cells, patient-derived organoids and xenograft mice. RESULTS: Faecal L. lactis was depleted in patients with CRC. A new L. lactis strain was isolated from human stools and nomenclated as HkyuLL 10. HkyuLL 10 supplementation suppressed CRC tumourigenesis in Apc Min/+ mice, and this tumour-suppressing effect was confirmed in mice with carcinogen-induced CRC. Microbiota profiling revealed probiotic enrichment including Lactobacillus johnsonii in HkyuLL 10-treated mice. HkyuLL 10-CM significantly abrogated the growth of human CRC cells and patient-derived organoids. Such protective effect was attributed to HkyuLL 10-secreted proteins, and we identified that α-mannosidase was the functional protein. The antitumourigenic effect of α-mannosidase was demonstrated in human CRC cells and organoids, and its supplementation significantly reduced tumour growth in xenograft mice. CONCLUSION: HkyuLL 10 suppresses CRC tumourigenesis in mice through restoring gut microbiota and secreting functional protein α-mannosidase. HkyuLL 10 administration may serve as a prophylactic measure against CRC.

4.
Gut ; 73(7): 1052-1075, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38609165

RESUMO

The first British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS)-endorsed faecal microbiota transplant (FMT) guidelines were published in 2018. Over the past 5 years, there has been considerable growth in the evidence base (including publication of outcomes from large national FMT registries), necessitating an updated critical review of the literature and a second edition of the BSG/HIS FMT guidelines. These have been produced in accordance with National Institute for Health and Care Excellence-accredited methodology, thus have particular relevance for UK-based clinicians, but are intended to be of pertinence internationally. This second edition of the guidelines have been divided into recommendations, good practice points and recommendations against certain practices. With respect to FMT for Clostridioides difficile infection (CDI), key focus areas centred around timing of administration, increasing clinical experience of encapsulated FMT preparations and optimising donor screening. The latter topic is of particular relevance given the COVID-19 pandemic, and cases of patient morbidity and mortality resulting from FMT-related pathogen transmission. The guidelines also considered emergent literature on the use of FMT in non-CDI settings (including both gastrointestinal and non-gastrointestinal indications), reviewing relevant randomised controlled trials. Recommendations are provided regarding special areas (including compassionate FMT use), and considerations regarding the evolving landscape of FMT and microbiome therapeutics.


Assuntos
Infecções por Clostridium , Transplante de Microbiota Fecal , Gastroenterologia , Transplante de Microbiota Fecal/métodos , Humanos , Infecções por Clostridium/terapia , Gastroenterologia/normas , COVID-19/terapia , SARS-CoV-2 , Recidiva , Clostridioides difficile , Reino Unido , Sociedades Médicas
5.
Gut ; 73(5): 751-769, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38331563

RESUMO

OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is a major cause of global illness and death, most commonly caused by cigarette smoke. The mechanisms of pathogenesis remain poorly understood, limiting the development of effective therapies. The gastrointestinal microbiome has been implicated in chronic lung diseases via the gut-lung axis, but its role is unclear. DESIGN: Using an in vivo mouse model of cigarette smoke (CS)-induced COPD and faecal microbial transfer (FMT), we characterised the faecal microbiota using metagenomics, proteomics and metabolomics. Findings were correlated with airway and systemic inflammation, lung and gut histopathology and lung function. Complex carbohydrates were assessed in mice using a high resistant starch diet, and in 16 patients with COPD using a randomised, double-blind, placebo-controlled pilot study of inulin supplementation. RESULTS: FMT alleviated hallmark features of COPD (inflammation, alveolar destruction, impaired lung function), gastrointestinal pathology and systemic immune changes. Protective effects were additive to smoking cessation, and transfer of CS-associated microbiota after antibiotic-induced microbiome depletion was sufficient to increase lung inflammation while suppressing colonic immunity in the absence of CS exposure. Disease features correlated with the relative abundance of Muribaculaceae, Desulfovibrionaceae and Lachnospiraceae family members. Proteomics and metabolomics identified downregulation of glucose and starch metabolism in CS-associated microbiota, and supplementation of mice or human patients with complex carbohydrates improved disease outcomes. CONCLUSION: The gut microbiome contributes to COPD pathogenesis and can be targeted therapeutically.


Assuntos
Pneumonia , Doença Pulmonar Obstrutiva Crônica , Humanos , Camundongos , Animais , Doença Pulmonar Obstrutiva Crônica/etiologia , Pulmão/metabolismo , Pulmão/patologia , Pneumonia/etiologia , Inflamação/metabolismo , Carboidratos/farmacologia
6.
Gut ; 73(8): 1292-1301, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38839272

RESUMO

OBJECTIVE: There is a strong clinical association between IBD and primary sclerosing cholangitis (PSC), a chronic disease of the liver characterised by biliary inflammation that leads to strictures and fibrosis. Approximately 60%-80% of people with PSC will also develop IBD (PSC-IBD). One hypothesis explaining this association would be that PSC drives IBD. Therefore, our aim was to test this hypothesis and to decipher the underlying mechanism. DESIGN: Colitis severity was analysed in experimental mouse models of colitis and sclerosing cholangitis, and people with IBD and PSC-IBD. Foxp3+ Treg-cell infiltration was assessed by qPCR and flow cytometry. Microbiota profiling was carried out from faecal samples of people with IBD, PSC-IBD and mouse models recapitulating these diseases. Faecal microbiota samples collected from people with IBD and PSC-IBD were transplanted into germ-free mice followed by colitis induction. RESULTS: We show that sclerosing cholangitis attenuated IBD in mouse models. Mechanistically, sclerosing cholangitis causes an altered intestinal microbiota composition, which promotes Foxp3+ Treg-cell expansion, and thereby protects against IBD. Accordingly, sclerosing cholangitis promotes IBD in the absence of Foxp3+ Treg cells. Furthermore, people with PSC-IBD have an increased Foxp3+ expression in the colon and an overall milder IBD severity. Finally, by transplanting faecal microbiota into gnotobiotic mice, we showed that the intestinal microbiota of people with PSC protects against colitis. CONCLUSION: This study shows that PSC attenuates IBD and provides a comprehensive insight into the mechanisms involved in this effect.


Assuntos
Colangite Esclerosante , Modelos Animais de Doenças , Microbioma Gastrointestinal , Doenças Inflamatórias Intestinais , Linfócitos T Reguladores , Colangite Esclerosante/imunologia , Colangite Esclerosante/complicações , Colangite Esclerosante/microbiologia , Animais , Camundongos , Linfócitos T Reguladores/imunologia , Doenças Inflamatórias Intestinais/microbiologia , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/imunologia , Humanos , Fatores de Transcrição Forkhead/metabolismo , Colite/microbiologia , Colite/complicações , Masculino , Transplante de Microbiota Fecal , Feminino , Fezes/microbiologia , Camundongos Endogâmicos C57BL
7.
Gut ; 73(4): 613-621, 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38182137

RESUMO

OBJECTIVE: Contaminated duodenoscopes caused several hospital outbreaks. Despite efforts to reduce contamination rates, 15% of patient-ready duodenoscopes are still contaminated with gastrointestinal microorganisms. This study aimed to provide an overview of duodenoscope contamination over time, identify risk factors and study the effects of implemented interventions. DESIGN: Duodenoscope culture sets between March 2015 and June 2022 at a Dutch tertiary care centre were analysed. Contamination was defined as (1) the presence of microorganisms of oral or gastrointestinal origin (MGO) or (2) any other microorganism with ≥20 colony-forming units/20 mL (AM20). A logistic mixed effects model was used to identify risk factors and assess the effect of interventions, such as using duodenoscopes with disposable caps, replacing automated endoscope reprocessors (AER) and conducting audits in the endoscopy department. RESULTS: A total of 404 culture sets were analysed. The yearly contamination rate with MGO showed great variation, ranging from 14.3% to 47.5%. Contamination with AM20 increased up to 94.7% by 2022. For both MGO and AM20, the biopsy and suction channels were the most frequently contaminated duodenoscope components. The studied interventions, including audits, AER replacement and implementation of duodenoscopes with disposable caps, did not show a clear association with contamination rates. CONCLUSION: Duodenoscope contamination remains a significant problem, with high contamination rates despite several interventions. Reprocessing the biopsy and suction channels is especially challenging. Changes in the design of reusable duodenoscopes, such as enabling sterilisation or easily replaceable channels, are necessary to facilitate effective duodenoscope reprocessing and to eliminate the risk of duodenoscope-associated infections.


Assuntos
Infecção Hospitalar , Duodenoscópios , Humanos , Colangiopancreatografia Retrógrada Endoscópica , Infecção Hospitalar/prevenção & controle , Infecção Hospitalar/epidemiologia , Óxido de Magnésio , Estudos Retrospectivos , Centros de Atenção Terciária
8.
BMC Microbiol ; 24(1): 253, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38982403

RESUMO

BACKGROUND: Gut microbes play an important role in the growth and health of neonatal piglets. Probiotics can promote the healthy growth of neonatal piglets by regulating their gut microbes. The study investigated the effects of spraying Lactiplantibacillus plantarum P-8 (L. plantarum P-8) fermentation broth on the growth performance and gut microbes of neonatal piglets. RESULTS: The animals were randomly divided into probiotics groups (109 neonatal piglets) and control groups (113 neonatal piglets). The probiotics group was sprayed with L. plantarum P-8 fermented liquid from 3 day before the expected date of the sow to the 7-day-old of piglets, while the control group was sprayed with equal dose of PBS. Average daily gain (ADG), immune and antioxidant status and metagenome sequencing were used to assess the changes in growth performance and gut microbiota of neonatal piglets. The results showed that L. plantarum P-8 treatment significantly improved the average daily gain (P < 0.05) of neonatal piglets. L. plantarum P-8 increased the activities of CAT and SOD but reduced the levels of IL-2 and IL-6, effectively regulating the antioxidant capacity and immunity in neonatal piglets. L. plantarum P-8 adjusted the overall structure of gut microflora improving gut homeostasis to a certain extent, and significantly increased the relative abundance of gut beneficial bacteria such as L. mucosae and L. plantarum. CONCLUSION: Spraying L. plantarum P-8 can be a feasible and effective probiotic intervention not only improving the growth of neonatal piglets, regulating the antioxidant capacity and immunity of neonatal piglets, but also improving the gut homeostasis to a certain extent.


Assuntos
Animais Recém-Nascidos , Microbioma Gastrointestinal , Probióticos , Animais , Probióticos/administração & dosagem , Probióticos/farmacologia , Suínos , Microbioma Gastrointestinal/efeitos dos fármacos , Lactobacillus plantarum , Fermentação , Antioxidantes/metabolismo , Antioxidantes/administração & dosagem , Antioxidantes/farmacologia , Fezes/microbiologia
9.
J Nutr ; 154(4): 1298-1308, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38408729

RESUMO

BACKGROUND: Recent studies suggest that some nonnutritive sweeteners (NNS) have deleterious effects on the human gut microbiome (HGM). The effect of steviol glycosides on the HGM has not been well studied. OBJECTIVE: We aimed to evaluate the effects of stevia- compared with sucrose-sweetened beverages on the HGM and fecal short-chain fatty acid (SCFA) profiles. METHODS: Using a randomized, double-blinded, parallel-design study, n = 59 healthy adults [female/male, n = 36/23, aged 31±9 y, body mass index (BMI): 22.6±1.7 kg/m2] consumed 16 oz of a beverage containing either 25% of the acceptable daily intake (ADI) of stevia or 30 g of sucrose daily for 4 weeks followed by a 4-week washout. At weeks 0 (baseline), 4, and 8, the HGM was characterized via shotgun sequencing, fecal SCFA concentrations were measured using ultra-high performance liquid chromatography-tandem mass spectrometry and anthropometric measurements, fasting serum glucose, insulin and lipids, blood pressure, pulse, and 3-d diet records were obtained. RESULTS: There were no significant differences in the HGM or fecal SCFA between the stevia and sucrose groups at baseline (P > 0.05). At week 4 (after intervention), there were no significant differences in the HGM at the phylum, family, genus, or species level between the stevia and sucrose groups and no significant differences in fecal SCFA. At week 4, BMI had increased by 0.3 kg/m2 (P = 0.013) in sucrose compared with stevia, but all other anthropometric and cardiometabolic measures and food intake did not differ significantly (P > 0.05). At week 8 (after washout), there were no significant differences in the HGM, fecal SFCA, or any anthropometric or cardiometabolic measure between the stevia and sucrose groups (P > 0.05). CONCLUSIONS: Daily consumption of a beverage sweetened with 25% of the ADI of stevia for 4 weeks had no significant effects on the HGM, fecal SCFA, or fasting cardiometabolic measures, compared with daily consumption of a beverage sweetened with 30 g of sucrose. TRIAL REGISTRATION: clinicaltrials.gov as NCT05264636.


Assuntos
Doenças Cardiovasculares , Diterpenos do Tipo Caurano , Microbioma Gastrointestinal , Glucosídeos , Adoçantes não Calóricos , Stevia , Adulto , Humanos , Masculino , Feminino , Sacarose , Bebidas/análise , Stevia/química
10.
Cell Commun Signal ; 22(1): 268, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38745207

RESUMO

Ulcerative colitis (UC) is increasingly common, and it is gradually become a kind of global epidemic. UC is a type of inflammatory bowel disease (IBD), and it is a lifetime recurrent disease. UC as a common disease has become a financial burden for many people and has the potential to develop into cancer if not prevented or treated. There are multiple factors such as genetic factors, host immune system disorders, and environmental factors to cause UC. A growing body of research have suggested that intestinal microbiota as an environmental factor play an important role in the occurrence and development of UC. Meanwhile, evidence to date suggests that manipulating the gut microbiome may represent effective treatment for the prevention or management of UC. In addition, the main clinical drugs to treat UC are amino salicylate and corticosteroid. These clinical drugs always have some side effects and low success rate when treating patients with UC. Therefore, there is an urgent need for safe and efficient methods to treat UC. Based on this, probiotics and prebiotics may be a valuable treatment for UC. In order to promote the wide clinical application of probiotics and prebiotics in the treatment of UC. This review aims to summarize the recent literature as an aid to better understanding how the probiotics and prebiotics contributes to UC while evaluating and prospecting the therapeutic effect of the probiotics and prebiotics in the treatment of UC based on previous publications.


Assuntos
Colite Ulcerativa , Microbioma Gastrointestinal , Prebióticos , Probióticos , Humanos , Colite Ulcerativa/terapia , Colite Ulcerativa/microbiologia , Probióticos/uso terapêutico , Probióticos/administração & dosagem , Prebióticos/administração & dosagem , Animais
11.
Mol Cell Biochem ; 2024 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-38217838

RESUMO

The metabolism of long-chain polyunsaturated fatty acids (LCPUFAs) is closely associated with the risk and progression of colorectal cancer (CRC). This paper aims to investigate the role of LCPUFA in the crosstalk between intestinal microflora and macrophages, as well as the effects of these three parties on the progression of CRC. The metabolism and function of LCPUFA play important roles in regulating the composition of the human gut microflora and participating in the regulation of inflammation, ultimately affecting macrophage function and polarization, which is crucial in the tumor microenvironment. The effects of LCPUFA on cellular interactions between the two species can ultimately influence the progression of CRC. In this review, we explore the molecular mechanisms and clinical applications of LCPUFA in the interactions between intestinal microflora and intestinal macrophages, as well as its significance for CRC progression. Furthermore, we reveal the role of LCPUFA in the construction of the CRC microenvironment and explore the key nodes of the interactions between intestinal flora and intestinal macrophages in the environment. It provides potential targets for the metabolic diagnosis and treatment of CRC.

12.
Fish Shellfish Immunol ; 151: 109667, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38830520

RESUMO

For effective restoration, conservation of Ussruri whitefish Coregonus ussuriensis Berg and coping with global climate change, effects of environmental temperature on Ussruri whitefish urgently need to be explored. In current study, the effects of different acclimation temperatures on the growth, digestive physiology, antioxidant ability, liver transcriptional responses and intestinal microflora patterns of Ussruri whitefish were investigated. Ussruri whitefish (15.20 g ± 1.23 g) were reared for 42 days under different acclimation temperatures, i.e., 10, 13, 16, 19, 22 and 25 °C, respectively. Result first determined 28 °C as the semi-lethal temperature in order to design the temperature gradient test. Highest main gain rate (MGR) and specific growth rate (SGR) were observed in fish group having acclimation temperature of 19 °C. Significantly decrease (P < 0.05) in triglyceride (TG) content appeared at 19 °C as compared to the 10 °C and 13 °C temperature groups. 19 °C notablely increased protease activities of stomach and intestine and intestinal lipase and amylase activities. 19 °C group obtained the highest activities of chloramphnicol acetyltransferase (CAT) and total antioxidant capacity (T-AOC) and higher activities of superoxide dismutase (SOD). The intestinal microflora composition was most conducive to maintaining overall intestinal health when the temperature was 19 °C, compared to 10 °C and 25 °C. Ussruri whitefish exposed to 10 °C and 25 °C possessed the lower Lactobacillus abundance compared to exposure to 19 °C. Temperature down to 10 °C or up to 25 °C, respectively, triggered cold stress and heat stress, which leading to impairment in intestinal digestion, liver antioxidant capacity and intestinal microflora structure. Liver transcriptome response to 10 °C, 19 °C and 25 °C revealed that Ussruri whitefish might require the initiation of endoplasmic reticulum stress to correct protein damage from cold-temperature and high-temperature stress, and it was speculated that DNAJB11 could be regarded as a biomarker of cold stress response.Based on the quadratic regression analysis of MGR and SGR against temperature, the optimal acclamation temperature were, respectively, 18.0 °C and 18.1 °C. Our findings provide valuable theoretical insights for an in-depth understanding of temperature acclimation mechanisms and laid the foundation for conservation and development of Ussruri whitefish germplasm resources.


Assuntos
Aclimatação , Antioxidantes , Digestão , Microbioma Gastrointestinal , Fígado , Salmonidae , Transcriptoma , Animais , Antioxidantes/metabolismo , Salmonidae/fisiologia , Salmonidae/genética , Temperatura
13.
Fish Shellfish Immunol ; : 109790, 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-39059563

RESUMO

Grass carp (Ctenopharyngodon idella) is an intensively cultured and economically important herbivorous fish species in China, but its culture is often impacted by Aeromonas pathogens such as Aeromonas hydrophila and Aeromonas veronii. In this study, healthy grass carp were separately infected with A. hydrophila or A. veronii for 12, 24, 48 or 72 h. The results showed that the mRNA expression levels of intestinal inflammatory factors (tnf-α, il-1ß and il-8), complement factors (c3 and c4), antimicrobial peptides (hepcidin, nk-lysin and ß-defensin-1), immunoglobulins (igm and igt), and immune pathway-related signaling molecules (tlr1, tlr2, tlr4, myd88, irak4, irak1, traf6, nf-κb p65 and ap-1) were differentially upregulated in response to A. hydrophila and A. veronii challenge. Additionally, the expression levels of the intestinal pro-apoptotic genes tnfr1, tnfr2, tradd, caspase-8, caspase-3 and bax were significantly increased, whereas the expression of the inhibitory factor bcl-2 was significantly downregulated, indicating that Aeromonas infection significantly induced apoptosis in the intestine of grass carp. Moreover, the expression of intestinal tight junction proteins (occludin, zo-1, claudin b and claudin c) was significantly decreased after infection with Aeromonas. Histopathological analysis indicated the Aeromonas challenge caused severe damage to the intestinal villi with adhesions and detachment of intestinal villi accompanied by severe inflammatory cell infiltration at 12 h and 72 h. The 16SrRNA sequencing results showed that Aeromonas infection significantly altered the structure of the intestinal microflora of the grass carp at the phylum (Proteobacteria, Fusobacteria, Bacteroidetes and Firmicutes) and genus (Proteus, Cetobacterium, Bacteroides, and Aeromonas) levels. Take together, the findings of this study revealed that Aeromonas infection induces an intestinal immune response, triggers cell apoptosis, destroys physical barriers and alters microflora structure in the intestine of juvenile grass carp; the results will help to reveal the pathogenesis of intestinal bacterial diseases in grass carp.

14.
Fish Shellfish Immunol ; 148: 109521, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38552889

RESUMO

In mammals, ß-catenin participates in innate immune process through interaction with NF-κB signaling pathway. However, its role in teleost immune processes remains largely unknown. We aimed to clarify the function of ß-catenin in the natural defense mechanism of Qi river crucian carp (Carassius auratus). ß-catenin exhibited a ubiquitous expression pattern in adult fish, as indicated by real-time PCR analysis. Following lipopolysaccharide (LPS), Polyinosinic-polycytidylic acid (polyI: C) and Aeromonas hydrophila (A. hydrophila) challenges, ß-catenin increased in gill, intestine, liver and kidney, indicating that ß-catenin likely plays a pivotal role in the immune response against pathogen infiltration. Inhibition of the ß-catenin pathway using FH535, an inhibitor of Wnt/ß-catenin pathway, resulting in pathological damage of the gill, intestine, liver and kidney, significant decrease of innate immune factors (C3, defb3, LYZ-C, INF-γ), upregulation of inflammatory factors (NF-κB, TNF-α, IL-1, IL-8), and downregulation of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and catalase (CAT) activities, increase of Malondialdehyde (MDA) content. Following A. hydrophila invasion, the mortality rate in the FH535 treatment group exceeded that of the control group. In addition, the diversity of intestinal microflora decreased and the community structure was uneven after FH535 treatment. In summary, our findings strongly suggest that ß-catenin plays a vital role in combating pathogen invasion and regulating intestinal flora in Qi river crucian carp.


Assuntos
Carpas , Doenças dos Peixes , Microbioma Gastrointestinal , Infecções por Bactérias Gram-Negativas , Sulfonamidas , Animais , Carpa Dourada/genética , Carpa Dourada/metabolismo , Carpas/genética , Carpas/metabolismo , NF-kappa B , Rios , beta Catenina/genética , Qi , Imunidade Inata/genética , Antioxidantes , Aeromonas hydrophila/fisiologia , Proteínas de Peixes , Infecções por Bactérias Gram-Negativas/veterinária , Mamíferos/metabolismo
15.
Environ Sci Technol ; 58(20): 8643-8653, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38676641

RESUMO

Antimicrobial nanomaterials frequently induce inflammatory reactions within lung tissues and prompt apoptosis in lung cells, yielding a paradox due to the inherent anti-inflammatory character of apoptosis. This paradox accentuates the elusive nature of the signaling cascade underlying nanoparticle (NP)-induced pulmonary inflammation. In this study, we unveil the pivotal role of nano-microflora interactions, serving as the crucial instigator in the signaling axis of NP-induced lung inflammation. Employing pulmonary microflora-deficient mice, we provide compelling evidence that a representative antimicrobial nanomaterial, silver (Ag) NPs, triggers substantial motility impairment, disrupts quorum sensing, and incites DNA leakage from pulmonary microflora. Subsequently, the liberated DNA molecules recruit caspase-1, precipitating the release of proinflammatory cytokines and activating N-terminal gasdermin D (GSDMD) to initiate pyroptosis in macrophages. This pyroptotic cascade culminates in the emergence of severe pulmonary inflammation. Our exploration establishes a comprehensive mechanistic axis that interlinks the antimicrobial activity of Ag NPs, perturbations in pulmonary microflora, bacterial DNA release, macrophage pyroptosis, and consequent lung inflammation, which helps to gain an in-depth understanding of the toxic effects triggered by environmental NPs.


Assuntos
Pneumonia , Piroptose , Piroptose/efeitos dos fármacos , Camundongos , Animais , Pneumonia/induzido quimicamente , Pneumonia/patologia , Prata/toxicidade , Nanopartículas Metálicas/toxicidade , Macrófagos/efeitos dos fármacos , Inflamação
16.
J Biochem Mol Toxicol ; 38(1): e23525, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37665681

RESUMO

Colon cancer is a serious health problem across the globe with various dietary lifestyle modifications. It arises as an inflammation mediated crypts in the colon epithelial cells and undergoes uncontrolled cell division and proliferation. Bacterial enzymes contribute to a major outbreak in colon cancer development upon the release of toxic metabolites from the gut microflora. Pathogen associated molecular patterns and damage associated molecular patterns triggers the NLPR3 inflammasome pathways that releases pro-inflammatory cytokines to induce cancer of the colon. Contributing to this, specific chemokines and receptor complexes attribute to cellular proliferation and metastasis. Bacterial enzymes synergistically attack the colon mucosa and degenerate the cellular integrity causing lysosomal discharge. These factors further instigate the Tol like receptors (TLRs) and Nod like receptors (NLRs) to promote angiogenesis and supply nutrients for the cancer cells. Myrtenal, a monoterpene, is gaining more importance in recent times and it is being widely utilized against many diseases such as cancers, neurodegenerative diseases and diabetes. Based on the research data's, the reviews focus on the anticancer property of myrtenal by emphasizing its therapeutic properties which downregulate the inflammasome pathways and other signalling pathways. Combination therapy is gaining more importance as they can target every variant in the cellular stress condition. Clinical studies with compounds like myrtenal of the monoterpenes family is provided with positive results which might open an effective anticancer drug therapy. This review highlights myrtenal and its biological potency as a cost effective drug for prevention and treatment of colon cancer.


Assuntos
Antineoplásicos , Monoterpenos Bicíclicos , Neoplasias do Colo , Humanos , Inflamassomos , Citocinas , Antineoplásicos/farmacologia , Neoplasias do Colo/tratamento farmacológico
17.
Environ Res ; 245: 118020, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38151149

RESUMO

Enhancing crop yield to accommodate the ever-increasing world population has become critical, and diminishing arable land has pressured current agricultural practices. Intensive farming methods have been using more pesticides and insecticides (biocides), culminating in soil deposition, negatively impacting the microbiome. Hence, a deeper understanding of the interaction and impact of pesticides and insecticides on microbial communities is required for the scientific community. This review highlights the recent findings concerning the possible impacts of biocides on various soil microorganisms and their diversity. This review's bibliometric analysis emphasised the recent developments' statistics based on the Scopus document search. Pesticides and insecticides are reported to degrade microbes' structure, cellular processes, and distinct biochemical reactions at cellular and biochemical levels. Several biocides disrupt the relationship between plants and their microbial symbionts, hindering beneficial biological activities that are widely discussed. Most microbial target sites of or receptors are biomolecules, and biocides bind with the receptor through a ligand-based mechanism. The biomarker action mechanism in response to biocides relies on activating the receptor site by specific biochemical interactions. The production of electrophilic or nucleophilic species, free radicals, and redox-reactive agents are the significant factors of biocide's metabolic reaction. Most studies considered for the review reported the negative impact of biocides on the soil microbial community; hence, technological development is required regarding eco-friendly pesticide and insecticide, which has less or no impact on the soil microbial community.


Assuntos
Desinfetantes , Herbicidas , Inseticidas , Microbiota , Praguicidas , Inseticidas/toxicidade , Herbicidas/toxicidade , Solo/química , Microbiologia do Solo
18.
Digestion ; 105(3): 201-212, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38350430

RESUMO

INTRODUCTION: Stress and lifestyle factors impact the course of Crohn's disease (CD). Our primary objective was to assess whether patients with CD benefit from a mind-body-medicine stress management and lifestyle modification (MBM) program. METHODS: This 9-month two-arm pilot trial was conducted in Bamberg, Germany (2020-2021). Patients (18-75 years) with mild to moderate activity of CD and stable medication were enrolled and randomly assigned to either a 10-week MBM program (intervention group, IG) or a single 90-min education session (waiting list control group, CG). Primary endpoints were quality of life (IBDQ) and disease activity (HBI). Secondary endpoints were emotional distress, core self-evaluation, and inflammatory biomarkers 3 and 9 months after baseline assessment. RESULTS: We analyzed data from 37 patients (IG: n = 19, mean ± SD age 49.6 ± 13.1 years, 68% female; CG: 18, 46.8 ± 11.4, 67% female). Immediately after the intervention, 79% (IG) and 44% (CG) experienced a clinically relevant improvement (IBDQ score ≥16 points). This was similar after 9 months (63% vs. 44%). There was no difference in disease activity (3 months: p = 0.082, 95% CI -1.3 to 2.6; 9 months: p = 0.251, 95% CI -1.2 to 2.5). Secondary outcomes indicated improvements in emotional distress, core self-evaluation, erythrocyte sedimentation rate after three and in emotional distress, T-cell profiling in the blood, and fecal lactoferrin and calprotectin group after 9 months in the IG. CONCLUSION: Our study suggested benefits of a multimodal stress management and lifestyle modification program for patients with CD. Larger trials are needed to determine if the program can supplement or at least partially replace pharmacological treatment approaches.


Assuntos
Doença de Crohn , Qualidade de Vida , Estresse Psicológico , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Doença de Crohn/terapia , Doença de Crohn/psicologia , Adulto , Estresse Psicológico/terapia , Estresse Psicológico/etiologia , Seguimentos , Alemanha , Idoso , Resultado do Tratamento , Terapias Mente-Corpo/métodos , Adulto Jovem , Adolescente , Índice de Gravidade de Doença , Estilo de Vida , Comportamento de Redução do Risco , Terapia Combinada/métodos
19.
Ecotoxicol Environ Saf ; 277: 116384, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38657451

RESUMO

It's of great challenge to address for heavy metal-contaminated soil. Once the farmland is contaminated with heavy metals, the microbial ecology of the plant rhizosphere will change, which in turn impacts crop productivity and quality. However, few studies have explored the effects of heavy metals on plant rhizosphere microbes in farmland and the role that plant cultivation plays in such a phytoremediation practice. In this study, the impacts of comfrey (Symphytum officinale L.) cultivation and the stresses of cadmium/zinc (Cd/Zn) on rhizosphere soil microflora were examined. Microbial DNA was collected from soils to evaluate the prevalence of bacteria and fungi communities in rhizosphere soils. High-throughput 16 S rRNA sequencing was used to determine the diversity of the bacterial and fungal communities. The results showed that growing comfrey on polluted soils reduced the levels of Cd and Zn from the vertical profile. Both the comfrey growth and Cd/Zn stresses affected the community of rhizosphere microorganisms (bacteria or fungi). Additionally, the analysis of PCoA and NMDS indicated that the cultivation of comfrey significantly changed the bacterial composition and structure of unpolluted soil. Comfrey cultivation in polluted and unpolluted soils did not result in much variance in the fungi's species composition, but the fungal compositions of the two-type soils were noticeably different. This work provided a better understanding of the impacts of Cd/Zn stresses and comfrey cultivation on rhizosphere microbial community, as well as new insight into phytoremediation of heavy metal-contaminated soils.


Assuntos
Bactérias , Biodegradação Ambiental , Cádmio , Fungos , Rizosfera , Microbiologia do Solo , Poluentes do Solo , Zinco , Cádmio/toxicidade , Zinco/toxicidade , Poluentes do Solo/toxicidade , Fungos/efeitos dos fármacos , Bactérias/efeitos dos fármacos , Bactérias/genética , Solo/química , Microbiota/efeitos dos fármacos , Metais Pesados/toxicidade , Estresse Fisiológico
20.
Ecotoxicol Environ Saf ; 270: 115883, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38157802

RESUMO

Cadmium (Cd) is a ubiquitous environmental pollutant, and Cd exposure harms human health, agriculture, and animal husbandry. The present study aimed to investigate the potential protective effect of dietary supplementation of calcium tetraborate (CTB) on productive performance, oxidative stress, cecal microflora, and histopathological changes in quail exposed to Cd. A total of one hundred twenty, 6-week-old Japanese quail (four females and two males/replicate) were divided into four groups (30 quails/group): the control group (feeding basic diet), CTB group (basic diet containing 300 mg/kg CaB4O7, 22.14% elemental B/kg diet), the Cd group (basic diet containing 100 mg/kg cadmium chloride (CdCl2) (total Cd content of 92.1 mg/kg)) and the CTB + Cd group (basic diet containing 300 mg/kg CTB and 100 mg/kg CdCl2). The results showed that Cd exposure caused decreased performance, increased the proportion of broken and soft-shelled eggs, induced oxidative stress, affected cecal microflora, epicardial hemorrhages in the heart, focal necrosis in the liver, degeneration in the kidneys, and degenerated and necrotic seminiferous tubules in the testicles. CTB prevented Cd-induced oxidative stress in liver tissue by increasing total antioxidant status and reducing total oxidant status. In addition, CTB improved egg production and feed conversion ratio (FCR). CTB protected the cecal microflora by inhibiting Enterobacteriaceae and promoting Lactobacillus. CTB also reduced Cd-induced histopathological damage in the heart, liver, kidneys, and testicles. In conclusion, these findings suggest that CTB could be used in Cd-challenged quail, and this compound provides new insights into the toxicity of environmental Cd.


Assuntos
Boratos , Cádmio , Microbioma Gastrointestinal , Animais , Feminino , Masculino , Humanos , Cádmio/toxicidade , Codorniz , Cálcio/farmacologia , Coturnix , Dieta , Estresse Oxidativo , Suplementos Nutricionais/análise , Ração Animal/análise
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