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Hepatocellular carcinoma (HCC), one of the leading causes of cancerrelated mortality worldwide, is challenging to identify in its early stages and prone to metastasis, and the prognosis of patients with this disease is poor. Treatment options for HCC are limited, with even radical treatments being associated with a risk of recurrence or transformation in the short term. Furthermore, the multityrosine kinase inhibitors approved for firstline therapy have marked drawbacks, including drug resistance and side effects. The rise and breakthrough of immune checkpoint inhibitors (ICIs) have provided a novel direction for HCC immunotherapy but these have the drawback of low response rates. Since avoiding apoptosis is a universal feature of cancer, the induction of nonapoptotic regulatory cell death (NARCD) is a novel strategy for HCC immunotherapy. At present, NARCD pathways, including ferroptosis, pyroptosis and necroptosis, are novel potential forms of immunogenic cell death, which have synergistic effects with antitumor immunity, transforming immune 'cold' tumors into immune 'hot' tumors and exerting antitumor effects. Therefore, these pathways may be targeted as a novel treatment strategy for HCC. In the present review, the roles of ferroptosis, pyroptosis and necroptosis in antitumor immunity in HCC are discussed, and the relevant targets and signaling pathways, and the current status of combined therapy with ICIs are summarized. The prospects of targeting ferroptosis, pyroptosis and necroptosis in HCC immunotherapy are also considered.
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Carcinoma Hepatocelular , Ferroptose , Imunoterapia , Neoplasias Hepáticas , Necroptose , Piroptose , Humanos , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/patologia , Piroptose/efeitos dos fármacos , Piroptose/imunologia , Ferroptose/efeitos dos fármacos , Necroptose/imunologia , Necroptose/efeitos dos fármacos , Imunoterapia/métodos , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/farmacologia , Transdução de Sinais/efeitos dos fármacos , AnimaisRESUMO
Men are inevitably plagued by prostate disease throughout their lives. However, the understanding of the pathogenesis of prostate diseases is still limited. In the 1960s, McNeal proposed the theory of prostate zones: the prostate was divided into three main zones: transition zone, central zone, and peripheral zone. Over the past 50 years, significant differences between different prostate zones have been gradually revealed. We summarized the most significant differences in different zones of the prostate. For the first time, we proposed the "apparent difference in prostate zones" concept. This new concept has been proposed to understand the different zones of the prostate better. It also provided new ideas for exploring the susceptibility of lesions in different prostate zones. Despite the reported differences between zones, the treatment of prostate-related diseases remains partition agnostic. Therefore, we also discussed the clinical significance of the "apparent difference in the prostate zone" and emphasized the necessity of prostate zones.
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Próstata , Hiperplasia Prostática , Neoplasias da Próstata , Prostatite , Humanos , Masculino , Neoplasias da Próstata/patologia , Próstata/patologia , Suscetibilidade a DoençasRESUMO
A novel promoter system for glycosylation is described. A catalytic amount of thiourea and Cu(OTf)2 together with a slight excess of N-iodosuccinimide synergistically promotes glycosylation at room temperature. The combination of reagents applies to some 2-azidoselenoglycoside and thioglycoside donors. A wide range of alcoholic acceptors underwent smooth conversion to O-(2-azido)glycosides with good stereoselectivities. In addition, the value of this method has been highlighted by its convenient operation and outstanding functional group compatibility.
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PURPOSES: The influence of gender on the epidemiology of and outcome from SA-AKI in ICU has not been fully clarified. Our aim is to elucidate these differences. METHODS: This study included adult patients with sepsis in MIMIC IV (V 2.2), and propensity matching analysis, cox regression and logistic regression were used to analyze gender differences in incidence, mortality and organ support rate. RESULTS: Of the 24,467 patients included in the cohort, 18,128 were retained after propensity score matching. In the matched cohort, the incidence of SA-AKI in males is higher than that in females (58.6% vs. 56.2%; P = 0.001).males were associated with a higher risk of SA-AKI (OR:1.07(1.01-1.14), P = 0.026;adjusted OR:1.07(1.01-1.14), P < 0.033).In SA-AKI patients, males were associated with a lower risk of ICU mortality(HR:0.803(0.721-0.893), P < 0.001;adjusted HR:0.836(0.746-0.937), P = 0.002) and in-hospital mortality(HR: 0.820(0.748-0.899), P < 0.001;adjusted HR:0.853(0.775-0.938), P = 0.003).there were no statistically significant differences between male and female patients in 1-year all-cause mortality (36.9% vs. 35.8%, P = 0.12), kidney replacement therapy rate (7.8% vs.7.4%, P = 0.547), mechanical ventilation rate 64.8% vs.63.9%, P = 0.369), and usage of vasoactive drugs (55.4% vs. 54.6%, P = 0.418). CONCLUSIONS: Gender may affect the incidence and outcomes of SA-AKI, further research is needed to fully understand the impact of gender on SA-AKI patients.
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Injúria Renal Aguda , Sepse , Adulto , Humanos , Masculino , Feminino , Estudos de Coortes , Estudos Retrospectivos , Unidades de Terapia Intensiva , Fatores de Risco , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/terapia , Sepse/complicações , Sepse/epidemiologiaRESUMO
BACKGROUND: Dressing change is the most important part of postoperative wound care. The aim of this study was to evaluate whether a more effective, simple and less painful method of dressing change for anal fistulas could be found without the need for debridement and packing. Data related to postoperative recovery were recorded at postoperative days 3, 7, 14, 21 and 180. METHODS: In this experiment, 76 subjects diagnosed with high anal fistula were randomly divided into a simplified dressing change (SDC) group and a traditional debridement dressing change(TDDC) group according to a ratio of 1:1. RESULTS: The SDC group had significantly fewer pain scores, bleeding rates, dressing change times, inpatient days and lower average inpatient costs than the TDDC group. There were no significant differences in wound healing time, area and depth and Wexner score between the two groups. CONCLUSIONS: Studies have shown that the use of simplified dressing changes does not affect cure or recurrence rates, but significantly reduces dressing change times and pain during changes, reducing patient inpatient length of stay and costs.
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Fístula Retal , Humanos , Estudos Prospectivos , Fístula Retal/cirurgia , Cicatrização , Dor , Bandagens , Resultado do TratamentoRESUMO
Objective: The clinical efficacy of perioperative chemotherapy regimen (rifampicin, doxycycline, levofloxacin, ceftriaxone) was evaluated for lumbar brucellosis spondylitis patients with neurological injury. Methods: In Beijing Ditan Hospital affiliated with Capital Medical University, 32 patients with lumbar brucellosis spondylitis underwent surgery and triple perioperative chemotherapy (rifampicin, doxycycline, levofloxacin) between 2011 and 2021 due to neurological injury, and 34 patients matched up with the triple group underwent rifampicin, doxycycline, levofloxacin, and ceftriaxone. Both groups were compared in terms of changes in inflammation index, low back/leg pain, lumbar function, neurological function, and adverse drug reactions. Results: There was no significant difference in erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), low back pain visual analogue scale (VAS), leg pain VAS, lumbar Oswestry disability index (ODI) and nerve function injury rate between the two groups before chemotherapy (P>0.05). The ESR, CRP at 1 week and 2 weeks after chemotherapy and 1 week, 2 weeks, 1 month postoperatively in the quadruple group were significantly lower than those in the triple group, which is the same to ESR 3 months postoperatively (P<0.05). The low back pain VAS, leg pain VAS and lumbar ODI in the quadruple group were significantly lower than those in the triple group at 1 month and 3 months postoperatively (P<0.05). The recovery rate of neurological function in the quadruple group was significantly higher than that in the triple group at 3 and 6 months postoperatively (P<0.05). Both groups did not experience significantly different perioperative and postoperative adverse reactions (P>0.05). Conclusion: For lumbar brucellosis spondylitis with neurological injury, quadruple perioperative chemotherapy of rifampicin, doxycycline, levofloxacin and ceftriaxone can significantly reduce perioperative inflammation, and improve low back/leg pain, as well as promoting neurological function recovery in the short term.
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Brucelose , Dor Lombar , Espondilite , Humanos , Doxiciclina , Rifampina , Levofloxacino/uso terapêutico , Ceftriaxona , Vértebras Lombares/cirurgia , Resultado do Tratamento , Brucelose/tratamento farmacológico , Inflamação , Estudos RetrospectivosRESUMO
PURPOSES: Low HDL-C is associated with an increased risk of sepsis-associated AKI and subsequent decline in eGFR. HDL-C possesses anti-inflammatory, antioxidant, and endothelial repair-promoting properties. The use of Apo A-I mimetic peptides, which are the main structural components of HDL-C, has been shown to improve renal function in animal models of sepsis. However, the diagnostic value of low HDL-C in persistent sepsis-associated AKI remains unclear. METHODS: This is a retrospective cohort study based on MIMIC IV (V 2.2). The study population consisted of all adult septic patients admitted to the Beth Israel Deaconess Medical Center Intensive Care Unit from 2008 to 2019, with plasma HDL-C measured within 24 h of ICU admission. The primary endpoint was persistent severe sepsis-associated acute kidney injury (SA-AKI) and the secondary endpoint is kidney replacement therapy (KRT). Logistic regression was used to assess the correlation between HDL-C and persistent severe SA-AKI and KRT, and receiver operating characteristic (ROC) curve analysis was performed to evaluate predictive ability. RESULTS: A total of 604 cases of SA-AKI patients were included in the analysis, among which 88 cases (14.5%) experienced persistent severe SA-AKI. The median (IQR) HDL-C level in the group with persistent severe SA-AKI was lower (33.0 [24.0-45.5]) compared to the non-persistent severe SA-AKI group (42.0 [31.0-53.0]). However, HDL-C showed poor discriminatory ability with an AUROC [95%CI] of 0.62 [0.56-0.69]. Clinical prediction models based on serum creatinine concentration, 24-h creatinine change, APSIIIscore, lactate levels, APTT, and heart rate performed well in predicting persistent severe SA-AKI with an AUROC [95%CI] of 0.876 [0.84-0.91]. However, adding HDL-C to this model did not improve predictive performance. CONCLUSIONS: The plasma HDL-C measured within 24 h after admission to the ICU does not provide a good prediction for persistent severe SA-AKI, and it does not improve the clinical predictive ability compared to conventional variables.
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Injúria Renal Aguda , Sepse , Adulto , Humanos , Estudos Retrospectivos , Biomarcadores , Sepse/diagnóstico , Unidades de Terapia Intensiva , Curva ROC , Injúria Renal Aguda/etiologia , CreatininaRESUMO
Alcohol consumption alters gut microflora and damages intestinal tight junction barriers, which may affect arsenic (As) oral bioavailability. In this study, mice were exposed to arsenate in the diet (6 µg/g) over a 3-week period and gavaged daily with Chinese liquor (0.05 or 0.10 mL per mouse per day). Following ingestion, 78.0% and 72.9% of the total As intake was absorbed and excreted via urine when co-exposed with liquor at daily doses of 0.05 or 0.10 mL, significantly greater than when As was supplied alone (44.7%). Alcohol co-exposure significantly altered gut microbiota but did not significantly alter As biotransformation in the intestinal tract or tissue. Significantly lower relative mRNA expression was observed for genes encoding for tight junctions in the ileum of liquor co-exposed mice, contributing to greater As bioavailability attributable to enhanced As absorption via the intestinal paracellular pathway. However, As concentration in the liver, kidney, and intestinal tissue of liquor-treated mice was decreased by 24.4%-42.6%, 27.5%-38.1%, and 28.1%-48.9% compared to control mice. This was likely due to greater renal glomerular filtration rate induced by alcohol, as suggested by significantly lower expression of genes encoding for renal tight junctions. In addition, in mice gavaged daily with 0.05 mL liquor, the serum antidiuretic hormone level was significantly lower than control mice (2.83 ± 0.59 vs. 5.40 ± 1.10 pg/mL), suggesting the diuretic function of alcohol consumption, which may facilitate As elimination via urine. These results highlight that alcohol consumption has a significant impact on the bioavailability and accumulation of As.
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Prebiotics may stimulate beneficial gut microorganisms. However, it remains unclear whether they can lower the oral bioavailability of early life arsenic (As) exposure via regulating gut microbiota and altering As biotransformation along the gastrointestinal (GI) tract. In this study, weanling mice were exposed to arsenate (iAsV) via diet (7.5 µg As g-1) amended with fructooligosaccharides (FOS), galactooligosaccharides (GOS), and inulin individually at 1% and 5% (w/w). Compared to As exposure control mice, As concentrations in mouse blood, liver, and kidneys and As urinary excretion factor (UEF) were reduced by 43.7%-74.1% when treated with 5% GOS. The decrease corresponded to a significant proliferation of Akkermansia and Psychrobacter, reduced percentage of inorganic arsenite (iAsIII) and iAsV by 47.4% and 65.4%, and increased proportion of DMAV in intestinal contents by 101% in the guts of mice treated with 5% GOS compared to the As control group. In contrast, FOS and inulin either at l% or 5% did not reduce As concentration in mouse blood, liver, and kidneys or As UEF. These results suggest that GOS supplementation may be a gut microbiota-regulating approach to lower early life As exposure via stimulating the growth of Akkermansia and Psychrobacter and enhancing As methylation in the GI tract.
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Arsênio , Microbioma Gastrointestinal , Camundongos , Animais , Inulina/metabolismo , Prebióticos , Fígado/metabolismoRESUMO
Nano-biochar is a novel material with emerging applications in various fields, including agriculture and environmental remediation. The potential risks of nano-biochar (N-BC) in the food chain necessitate further investigation. We studied the distribution and toxicity of N-BC in mice through dietary exposure. Using Balb/c mice, we assessed N-BC accumulation in organs and its impact on vital organs. Isotope analysis showed significant accumulation of 13C-N-BC in the liver (53.1%-55.9%), kidneys (4.0%-5.9%), and blood (9.2%-13.6%), with lesser amounts in the intestines (0.8%-1.2%) and stool (28.0%-28.1%). N-BC induced liver damage, evident by increased oxidative stress markers and histopathological changes. It disrupted tight junction proteins in the intestine, potentially allowing systemic entry. N-BC also influenced gut microbiota composition and metabolites. Our study provides insights into N-BC's distribution, toxicity, and environmental risks, urging further research on its implications for mammalian health and the ecosystem.
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Ecossistema , Recuperação e Remediação Ambiental , Animais , Camundongos , Dieta , Fígado , Oxirredução , Carvão Vegetal , MamíferosRESUMO
Arsenic (As) exposure has been related to many diseases, including cancers. Given the antioxidant and anti-inflammatory properties, the dietary supplementation of polyphenols may alleviate As toxicity. Based on a mouse bioassay, this study investigated the effects of chlorogenic acid (CA), quercetin (QC), tannic acid (TA), resveratrol (Res), and epigallocatechin gallate (EGCG) on As bioavailability, biotransformation, and toxicity. Intake of CA, QC, and EGCG significantly (p < 0.05) increased total As concentrations in liver (0.48-0.58 vs 0.27 mg kg-1) and kidneys (0.72-0.93 vs 0.59 mg kg-1) compared to control mice. Upregulated intestinal expression of phosphate transporters with QC and EGCG and proliferation of Lactobacillus in the gut of mice treated with CA and QC were observed, facilitating iAsV absorption via phosphate transporters and intestinal As solubility via organic acid metabolites. Although As bioavailability was elevated, serum levels of alpha fetoprotein and carcinoembryonic antigen of mice treated with all five polyphenols were reduced by 13.1-16.1% and 9.83-17.5%, suggesting reduced cancer risk. This was mainly due to higher DMAV (52.1-67.6% vs 31.4%) and lower iAsV contribution (4.95-10.7% vs 27.9%) in liver of mice treated with polyphenols. This study helps us develop dietary strategies to lower As toxicity.
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Arsênio , Polifenóis , Camundongos , Animais , Polifenóis/farmacologia , Arsênio/toxicidade , Disponibilidade Biológica , Suplementos Nutricionais , Biotransformação , Proteínas de Transporte de FosfatoRESUMO
Excessive osteoclast formation and bone resorption are related to osteolytic diseases. Delta drosophila homolog-like 2 (Dlk2), a member of the epidermal growth factor (EGF)-like superfamily, reportedly regulates adipocyte differentiation, but its roles in bone homeostasis are unclear. In this study, we demonstrated that Dlk2 deletion in osteoclasts significantly inhibited osteoclast formation in vitro and contributed to a high-bone-mass phenotype in vivo. Importantly, Dlk2 was shown to interact with synapse-associated protein 1 (Syap1), which regulates Akt phosphorylation at Ser473. Dlk2 deletion inhibited Syap1-mediated activation of the AktSer473, ERK1/2 and p38 signaling cascades. Additionally, Dlk2 deficiency exhibits increased bone mass in ovariectomized mice. Our results reveal the important roles of the Dlk2-Syap1 signaling pathway in osteoclast differentiation and osteoclast-related bone disorders.
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Osteoclastos , Proteínas Proto-Oncogênicas c-akt , Animais , Camundongos , Drosophila , Homeostase , Sistema de Sinalização das MAP Quinases , Transdução de SinaisRESUMO
Since the theory of modern anatomical partitioning of the prostate was proposed, the differences in the incidence and pathological parameters of prostate cancer between the peripheral zone and transition zone have been gradually revealed. It suggests that there are differences in the pathogenic pathways and molecular biology of prostate cancer between different regions of origin. Over the past decade, advances in sequencing technologies have revealed more about molecules, genomes, and cell types specific to the peripheral and transitional zones. In recent years, the innovation of spatial imaging and multiple-parameter magnetic resonance imaging has provided new technical support for the zonal study of prostate cancer. In this work, we reviewed all the research results and the latest research progress in the study of prostate cancer in the past two decades. We summarized and proposed several vital issues and focused directions for understanding the differences between peripheral and transitional zones in prostate cancer.
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Syringaldehyde (SD), a kind of flavonoid polyphenolic small molecule compound, has the antioxidant and anti-inflammatory properties. But it is unknown whether SD has properties on the treatment of rheumatoid arthritis (RA) by modulating dendritic cells (DCs). We explored the effect of SD on the maturation of DCs in vitro and in vivo. The results showed that SD significantly down-regulated the expression of CD86, CD40 and MHC II, decreased the secretion of TNF-α, IL-6, IL-12p40 and IL-23, and increased IL-10 secretion and antigen phagocytosis in vitro induced by lipopolysaccharides in a dose-dependent manner through reducing the activation of MAPK/NF-κB signaling pathways. SD also significantly inhibited the expression of CD86, CD40 and MHC II on DCs in vivo. Moreover, SD suppressed the expression of CCR7 and the in vivo migration of DCs. In arthritis mouse models induced by λ-carrageenan and complete Freund's adjuvant, SD significantly alleviated paw and joint oedema, reduced the levels of pro-inflammatory cytokines TNF-α and IL-6 and increased the level of IL-10 in serum. Interestingly, SD significantly decreased the numbers of type I helper T cells (Th1), Th2, Th17 and Th17/Th1-like (CD4+IFN-γ+IL-17A+), but increased the numbers of regulatory T cells (Tregs) in spleens of mice. Importantly, the numbers of CD11c+IL-23+ and CD11c+IL-6+ cells were negatively correlated with the numbers of Th17 and Th17/Th1-like. These results suggested that SD ameliorated mouse arthritis through inhibiting the differentiation of Th1, Th17 and Th17/Th1-like and promoting the generation of Tregs via regulation of DC maturation.
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Artrite , Interleucina-10 , Animais , Camundongos , Interleucina-10/metabolismo , Células Th1 , Interleucina-6/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Células Dendríticas , Citocinas/metabolismo , Diferenciação Celular , Interleucina-23/metabolismo , Camundongos Endogâmicos C57BLRESUMO
Prostate cancer is one of the more heterogeneous tumour types. In recent years, with the rapid development of single-cell sequencing and spatial transcriptome technologies, researchers have gained a more intuitive and comprehensive understanding of the heterogeneity of prostate cancer. Tumour-associated epithelial cells; cancer-associated fibroblasts; the complexity of the immune microenvironment, and the heterogeneity of the spatial distribution of tumour cells and other cancer-promoting molecules play a crucial role in the growth, invasion, and metastasis of prostate cancer. Single-cell multi-omics biotechnology, especially single-cell transcriptome sequencing, reveals the expression level of single cells with higher resolution and finely dissects the molecular characteristics of different tumour cells. We reviewed the recent literature on prostate cancer cells, focusing on single-cell RNA sequencing. And we analysed the heterogeneity and spatial distribution differences of different tumour cell types. We discussed the impact of novel single-cell omics technologies, such as rich omics exploration strategies, multi-omics joint analysis modes, and deep learning models, on future prostate cancer research. In this review, we have constructed a comprehensive catalogue of single-cell omics studies in prostate cancer. This article aimed to provide a more thorough understanding of the diagnosis and treatment of prostate cancer. We summarised and proposed several key issues and directions on applying single-cell multi-omics and spatial transcriptomics to understand the heterogeneity of prostate cancer. Finally, we discussed single-cell omics trends and future directions in prostate cancer.
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Neoplasias da Próstata , Microambiente Tumoral , Masculino , Humanos , Microambiente Tumoral/genética , Neoplasias da Próstata/genética , Próstata , Células Epiteliais , BiotecnologiaRESUMO
Oral, gut, and tumor microbiota have been implicated as important regulators in the carcinogenesis and progression of gastrointestinal malignancies. However, few studies focused on the existence and association of resident microbes within different body regions. Herein, we aim to reveal the durability of the oral-gut-tumor microbiome and its diagnostic performance in hepatocellular carcinoma (HCC). Our study included two cohorts: a retrospective discovery cohort of 364 HBV-HCC patients and 160 controls with oral or fecal samples, a prospective validation cohort of 91 cases, and 124 controls for matching samples, as well as 48 HBV, and 39 HBV-cirrhosis patients for gut microbial patterns examined by 16S rRNA gene sequencing. With the random forest analysis, 10 oral and 9 gut genera that could distinguish HCC from controls in the retrospective cohort were validated among the prospective matching participants, with area under the curve (AUC) values of 0.7971 and 0.8084, respectively. When influential taxa were merged, the AUC of the consistent classifier increased to 0.9405. The performance continued to improve to 0.9811 when combined with serum levels of alpha-fetoprotein (AFP). Specifically, microbial biomarkers represented by Streptococcus displayed a constantly increasing trend during the disease transition. Furthermore, the presence of several dominant microbiota species was confirmed in hepatic tumor and non-tumor tissues with fluorescence in situ hybridization (FISH) and 5 R 16S rRNA gene sequencing. Overall, our findings based on the oral-gut-tumor microbiota provide a reliable approach for the early detection of HCC.
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Carcinoma Hepatocelular , Microbioma Gastrointestinal , Neoplasias Hepáticas , Microbiota , Humanos , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/diagnóstico , Estudos Retrospectivos , RNA Ribossômico 16S/genética , Hibridização in Situ Fluorescente , Curva ROC , Microbioma Gastrointestinal/genéticaRESUMO
Helicobacter pylori (H. pylori), as a harmful bacteria associated with gastric cancer, can have adverse effects on human normal flora and metabolism. However, the effects of H. pylori on human metabolism have not been fully elucidated. The 13 C breathing test was used as the basis for distinguishing negative and positive groups. Serum samples were collected from the two groups for targeted quantitative metabolomics detection; multidimensional statistics were used, including partial least squares discriminant analysis (PLS-DA), principal component analysis (PCA), orthogonal partial least squares discriminant analysis (OPLS-DA), and differential metabolites were screened. Unidimensional statistics combined with multidimensional statistics were used to further screen potential biomarkers, and finally pathway analysis was performed. SPSS 21.0 software package was used for statistical analysis of experimental data. Multivariate statistical analysis such as PLS-DA, PCA, and OPLS-DA was performed using Simca-P 13.0 to search for differential metabolites. This study confirmed that H. pylori caused significant changes in human metabolism. In this experiment, 211 metabolites were detected in the serum of the two groups. Multivariate statistical analysis showed that PCA of metabolites was not significantly different between the two groups. PLS-DA indicated that the serum of the two groups was well clustered. There were significant differences in metabolites between OPLS-DA groups. By setting the variable importance in projection (VIP) threshold as one and the corresponding P-value <0.05, a total of 40 metabolites were screened in this study. P <0.05 and â£log2FCâ£>0 (where FC is the fold change) were used together as a unidimensional statistical filter condition. The analysis found that the expression of 15 metabolites such as propionic acid, acetic acid, adipic acid increased, and the metabolism of six products such as deoxycholic acid (DCA), 4-hydroxyphenylpyruvic acid, pyruvic acid decreased. P <0.05, false discovery rate <0.5, â£log2FCâ£>1, and OPLSDA_VIP>1 were used together as a condition for filter screening potential biomarkers. Four potential biomarkers were screened, which were sebacic acid, isovaleric acid, DCA, and indole-3-carboxylic acid. Finally, the different metabolites were added to the pathway-associated metabolite sets (SMPDB) library for the corresponding pathway enrichment analysis. The significant abnormal metabolic pathways were taurine and subtaurine metabolism, tyrosine metabolism, glycolysis or gluconeogenesis, pyruvate metabolism, etc. This study shows that H. pylori has an impact on human metabolism. Not only a variety of metabolites have significant changes, but also metabolic pathways are abnormal, which may be the reason for the high risk of H. pylori causing gastric cancer.
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Helicobacter pylori , Neoplasias Gástricas , Humanos , Espectrometria de Massas em Tandem , Metabolômica/métodos , Cromatografia Líquida , Biomarcadores , Ácido AcéticoRESUMO
Microplastics exposure is a new human health crisis. Although progress in understanding health effects of microplastic exposure has been made, microplastic impacts on absorption of co-exposure toxic pollutants such as arsenic (As), i.e., oral bioavailability, remain unclear. Microplastic ingestion may interfere As biotransformation, gut microbiota, and/or gut metabolites, thereby affecting As oral bioavailability. Here, mice were exposed to arsenate (6 µg As g-1) alone and in combination with polyethylene particles of 30 and 200 µm (PE-30 and PE-200 having surface area of 2.17 × 103 and 3.23 × 102 cm2 g-1) in diet (2, 20, and 200 µg PE g-1) to determine the influence of microplastic co-ingestion on arsenic (As) oral bioavailability. By determining the percentage of cumulative As consumption recovered in urine of mice, As oral bioavailability increased significantly (P < 0.05) from 72.0 ± 5.41% to 89.7 ± 6.33% with PE-30 at 200 µg PE g-1 rather than with PE-200 at 2, 20, and 200 µg PE g-1 (58.5 ± 19.0%, 72.3 ± 6.28%, and 69.2 ± 17.8%). Both PE-30 and PE-200 exerted limited effects on pre- and post-absorption As biotransformation in intestinal content, intestine tissue, feces, and urine. They affected gut microbiota dose-dependently, with lower exposure concentrations having more pronounced effects. Consistent with the PE-30-specific As oral bioavailability increase, PE exposure significantly up-regulated gut metabolite expression, and PE-30 exerted greater effects than PE-200, suggesting that gut metabolite changes may contribute to As oral bioavailability increase. This was supported by 1.58-4.07-fold higher As solubility in the presence of up-regulated metabolites (e.g., amino acid derivatives, organic acids, and pyrimidines and purines) in the intestinal tract assessed by an in vitro assay. Our results suggested that microplastic exposure especially smaller particles may exacerbate the oral bioavailability of As, providing a new angle to understand health effects of microplastics.
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Arsênio , Microbioma Gastrointestinal , Humanos , Animais , Camundongos , Microplásticos/química , Plásticos/toxicidade , Disponibilidade Biológica , Arsênio/toxicidade , Compostos Orgânicos , Polietileno/farmacologiaRESUMO
Early-life arsenic (As) exposure is a particular health concern. However, it is unknown if As ingested early in life is more readily absorbed from the gastrointestinal (GI) tract, i.e., higher in oral bioavailability. Here, weanling (3-week) and adult (6-week-old) female mice were exposed to arsenate in the diet (10 µg g-1) over a 3-week period with As oral bioavailability estimated using As urinary excretion as the bioavailability endpoint. The As urinary excretion factor was 1.54-fold higher in weanling mice compared to adult mice (82.2 ± 7.29 versus 53.1 ± 3.73%), while weanling mice also showed 2.28-, 1.50-, 1.48-, and 1.89-fold higher As concentration in small intestine tissue, blood, liver, and kidneys, demonstrating significantly higher As oral bioavailability of early-life exposure. Compared to adult mice, weanling mice significantly differed in gut microbiota, but the difference did not lead to remarkable differences in As biotransformation in the GI tract or tissue and in overall gut metabolite composition. Although the expression of several metabolites (e.g., atrolactic acid, hydroxyphenyllactic acid, and xanthine) was up-regulated in weanling mice, they had limited ability to elevate As solubility in the intestinal tract. Compared to adult mice, the intestinal barrier function and intestinal expression of phosphate transporters responsible for arsenate absorption were similar in weanling mice. However, the small intestine of weanling mice was characterized by more defined intestinal villi with greater length and smaller width, providing a greater surface area for As to be absorbed across the GI barrier. The results highlight that early-life As exposure can be more readily absorbed, advancing the understanding of its health risk.
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Arsênio , Microbioma Gastrointestinal , Animais , Camundongos , Feminino , Arseniatos , Mucosa Intestinal/metabolismoRESUMO
Reducing lead (Pb) exposure via oral ingestion of contaminated soils is highly relevant for child health. Elevating dietary micronutrient iron (Fe) intake can reduce Pb oral bioavailability while being beneficial for child nutritional health. However, the practical performance of various Fe compounds was not assessed. Here, based on mouse bioassays, ten Fe compounds applied to diets (100-800 mg Fe kg-1) reduced Pb oral relative bioavailability (RBA) in two soils variedly depending on Fe forms. EDTA-FeNa was most efficient, which reduced Pb-RBA in a soil from 79.5 ± 14.7 % to 23.1 ± 2.72 % (71 % lower) at 100 mg Fe kg-1 in diet, more effective than other 9 compounds at equivalent or higher doses (3.6-68 % lower). When EDTA-FeNa, ferrous gluconate, ferric citrate, and ferrous bisglycinate were supplemented, Fe-Pb co-precipitation was not observed in the intestinal tract. EDTA-FeNa, ferrous gluconate, ferric citrate, and ferrous sulfate suppressed duodenal divalent metal transporter 1 (DMT1)mRNA relative expression similarly (27-68 % lower). In comparison, among ten compounds, EDTA-FeNa elevated Fe concentrations in mouse liver, kidney, and blood (1.50-2.69-fold higher) most efficiently, suggesting the most efficient Fe absorption that competed with Pb. In addition, EDTA was unique from other organic ligands, ingestion of which caused 12.0-fold higher Pb urinary excretion, decreasing Pb concentrations in mouse liver, kidney, and blood by 68-88 %. The two processes (Fe-Pb absorption competition and Pb urinary excretion with EDTA) interacted synergistically, leading to the lowest Pb absorption with EDTA-FeNa. The results provide evidence of a better inhibition of Pb absorption by EDTA-FeNa, highlighting that EDTA-FeNa may be the most appropriate supplement for intervention on human Pb exposure. Future researches are needed to assess the effectiveness of EDTA-FeNa for intervention on human Pb exposure.