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1.
Pharmacol Res ; : 106090, 2022 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-35065201

RESUMO

Evidence reveals that gut dysbiosis is involved in bidirectional interactions in gut-brain axis and participates in the progress of multiple disorders like anxiety. Gut microbes in early life are crucial for establishment of host health. We aimed to investigate whether early life probiotics Lactobacillus rhamnosus GG (LGG) colonization could relieve anxiety in adulthood through regulation of gut-brain axis. Live or fixed LGG was gavaged to C57BL/6 female mice from day 18 of pregnancy until natural birth, and newborn mice from day 1 to day 5 respectively. In this study, we found that live LGG could be effectively colonized in the intestine of offspring. LGG colonization increased intestinal villus length and colonic crypt depth, accompanied with barrier function protection before weaning. Microbiota composition by 16S rRNA sequencing showed that some beneficial bacteria, such as Akkermansia and Bifidobacteria, were abundant in LGG colonization group. The protective effect of LGG on gut microbiota persisted from weaning to adulthood. Intriguingly, behavioral results assessed by elevated plus mazed test and open field test demonstrated relief of anxiety-like behavior in adult LGG-colonized offspring. Mechanically, LGG colonization activated epithelial growth factor receptor (EGFR) and enhanced serotonin transporter (SERT) expression and modulated serotonergic system in the intestine, and increased brain-derived neurotrophic factor and γ-aminobutyric acid receptor levels in the hippocampus and amygdala. Blocking EGFR blunted LGG-induced the increased SERT and zonula occludens-1 expression. Collectively, early life LGG colonization could protect intestinal barrier of offspring and modulate gut-brain axis in association with relief of anxiety-like behavior in adulthood.

2.
J Environ Sci (China) ; 115: 140-148, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-34969444

RESUMO

Endemic fluorosis exists in almost all provinces of China. The long-term ingestion of groundwater containing high concentrations of fluoride is one of the main causes of fluorosis. We used artificial neural network to model the relationship between groundwater fluoride concentrations from throughout China and environmental variables such as climatic, geological. and soil parameters as proxy predictors. The results show that the accuracy and area under the receiver operating characteristic curve of the model in the test dataset are 80.5% and 0.86%, respectively, and climatic variables are the most effective predictors. Based on the artificial neural network model, a nationwide prediction risk map of fluoride concentrations exceeding 1.5 mg/L with a 0.5 × 0.5 arc minutes resolution was generated. The high risk areas are mainly located in western provinces of Xinjiang, Tibet, Qinghai, and Sichuan, and the northern provinces of Inner Mongolia, Hebei and Shandong. The total number of people estimated to be potentially at risk of fluorosis due to the use of untreated high fluoride groundwater as drinking water is about 89 million, or 6% of the population. The high fluoride groundwater risk map helps the authorities to prioritize areas requiring mitigation measures and thus facilitates the implementation of water improvement and defluoridation projects.


Assuntos
Água Potável , Água Subterrânea , Poluentes Químicos da Água , China , Fluoretos/análise , Humanos , Solo , Poluentes Químicos da Água/análise
3.
J Environ Manage ; 303: 114249, 2021 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-34891008

RESUMO

Geogenic iodine-contaminated groundwater represents a threat to public health in China. Identifying high-iodine areas is essential to guide the mitigation of this problem. Considering that traditional analytical techniques for iodine testing are generally time-consuming, laborious, and expensive, alternative methods are needed to supplement and enhance existing approaches. Therefore, we developed an artificial neural network (ANN) model and assessed its feasibility in terms of predicting high iodine levels in groundwater in China. A total of 22 indicators (including climate, topography, geology, and soil properties) and 3185 aggregated samples (measured groundwater iodine concentrations) were utilized to develop the ANN model. The results showed that the accuracy and area under the receiver operating characteristic curve of the model on the test dataset are 90.9% and 0.972, respectively, and climate and soil variables are the most effective predictors. Based on the prediction results, a high-resolution (1-km) nationwide prediction map of high-iodine groundwater was produced. The high-risk areas are mainly concentrated in the central provinces of Henan, Shaanxi, and Shanxi, the eastern provinces of Henan, Shandong, and Hebei, and the northeastern provinces of Liaoning, Jilin, and Heilongjiang. The total number of people estimated to potentially be at high-risk areas because they use untreated high-iodine groundwater as drinking water is approximately 30 million. Considering the growing demand for groundwater in China, this work can guide the prioritization of groundwater contamination mitigation efforts based on regional groundwater quality levels to enhance environmental management.

4.
Front Immunol ; 12: 700995, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34804005

RESUMO

The prevalence of inflammatory bowel disease (IBD) is increasing worldwide and correlates with dysregulated immune response because of gut microbiota dysbiosis. Some adverse early life events influence the establishment of the gut microbiota and act as risk factors for IBD. Prenatal maternal stress (PNMS) induces gut dysbiosis and perturbs the neuroimmune network of offspring. In this study, we aimed to investigate whether PNMS increases the susceptibility of offspring to colitis in adulthood. The related index was assessed during the weaning period and adulthood. We found that PNMS impaired the intestinal epithelial cell proliferation, goblet cell and Paneth cell differentiation, and mucosal barrier function in 3-week-old offspring. PNMS induced low-grade intestinal inflammation, but no signs of microscopic inflammatory changes were observed. Although there was no pronounced difference between the PNMS and control offspring in terms of their overall measures of alpha diversity for the gut microbiota, distinct microbial community changes characterized by increases in Desulfovibrio, Streptococcus, and Enterococcus and decreases in Bifidobacterium and Blautia were induced in the 3-week-old PNMS offspring. Notably, the overgrowth of Desulfovibrio persisted from the weaning period to adulthood, consistent with the results observed using fluorescence in situ hybridization in the colon mucosa. Mechanistically, the fecal microbiota transplantation experiment showed that the gut microbiota from the PNMS group impaired the intestinal barrier function and induced low-grade inflammation. The fecal bacterial solution from the PNMS group was more potent than that from the control group in inducing inflammation and gut barrier disruption in CaCo-2 cells. After treatment with a TNF-α inhibitor (adalimumab), no statistical difference in the indicators of inflammation and intestinal barrier function was observed between the two groups. Finally, exposure to PNMS remarkably increased the values of the histopathological parameters and the inflammatory cytokine production in a mouse model of experimental colitis in adulthood. These findings suggest that PNMS can inhibit intestinal development, impair the barrier function, and cause gut dysbiosis characterized by the persistent overgrowth of Desulfovibrio in the offspring, resulting in exacerbated experimental colitis in adulthood.

5.
Cancer Sci ; 2021 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-34811848

RESUMO

A high-fat diet (HFD) leads to long-term exposure to gut microbial metabolite secondary bile acids, such as deoxycholic acid (DCA), in the intestine, which is closely linked to colorectal cancer (CRC). Evidence reveals that vasculogenic mimicry (VM) is a critical event for the malignant transformation of cancer. Therefore, this study investigated the crucial roles of DCA in the regulation of VM and the progression of intestinal carcinogenesis. The effects of an HFD on VM formation and epithelial-mesenchymal transition (EMT) in human CRC tissues were investigated. The fecal DCA level was detected in HFD-treated Apcmin/+ mice. Then the effects of DCA on VM formation, EMT, and vascular endothelial growth factor receptor 2 (VEGFR2) signaling were evaluated in vitro and in vivo. Here we demonstrated that compared with a normal diet, an HFD exacerbated VM formation and EMT in CRC patients. An HFD could alter the composition of the gut microbiota and significantly increase the fecal DCA level in Apcmin/+ mice. More importantly, DCA promoted tumor cell proliferation, induced EMT, increased VM formation, and activated VEGFR2, which led to intestinal carcinogenesis. In addition, DCA enhanced the proliferation and migration of HCT-116 cells, and induced EMT process and vitro tube formation. Furthermore, the silence of VEGFR2 reduced DCA-induced EMT, VM formation, and migration. Collectively, our results indicated that microbial metabolite DCA promoted VM formation and EMT through VEGFR2 activation, which further exacerbated intestinal carcinogenesis.

6.
Food Funct ; 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34821899

RESUMO

Research has shown that maternal sucralose (MS) exposure alters the gut microbiota of offspring at weaning and predisposes the offspring to developing obesity, non-alcoholic fatty liver disease and metabolic syndrome later in life. However, the underlying mechanism remains unclear. Paneth cells are thought to critically influence the gut microbiota. This study aimed to investigate whether MS exposure induced Paneth cell defects and exacerbated gut dysbiosis of offspring. Female C57BL/6 mice were divided into the MS and control (water) groups during pregnancy and lactation. Progeny mice were fed a normal sucralose-free diet after weaning until adulthood. MS inhibited intestinal development and increased the expression of proinflammatory cytokines in the small intestines of 3-week-old progeny mice. MS increased the proportions of abnormal granule secretion by Paneth cells. The number of Paneth cells and mRNA expression of AMPs such as cryptdins and lysozyme were reduced in the MS group. MS disturbed the gut microbiota composition and diversity in the 3-week-old offspring mice. The relative abundances of pro-inflammatory bacteria, such as Desulfovibrionales, Helicobacter, Pasteurellales and Campylobacterales were significantly increased in the MS group, while anti-inflammatory bacteria, including Clostridium XI, were decreased. This dysbiosis continued into adulthood. These findings showed that MS exposure induced Paneth cell defects and exacerbated gut dysbiosis in offspring mice. Sucralose should be consumed with caution, especially during pregnancy and in early life.

7.
Cancer Lett ; 526: 225-235, 2021 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-34843863

RESUMO

Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer-related death worldwide. It involves the complex interactions between genetic factors, environmental exposure, and gut microbiota. Specific changes in the gut microbiome and metabolome have been described in CRC, supporting the critical role of gut microbiota dysbiosis and microbiota-related metabolites in the tumorigenesis process. Short-chain fatty acids (SCFAs), the principal metabolites generated from the gut microbial fermentation of insoluble dietary fiber, can directly activate G-protein-coupled receptors (GPCRs), inhibit histone deacetylases (HDACs), and serve as energy substrates to connect dietary patterns and gut microbiota, thereby improving the intestinal health. A significantly lower abundance of SCFAs and SCFA-producing bacteria has been demonstrated in CRC, and the supplementation of SCFA-producing probiotics can inhibit intestinal tumor development. SCFAs-guided modulation in both mouse and human CRC models augmented their responses to chemotherapy and immunotherapy. This review briefly summarizes the complex crosstalk between SCFAs and CRC, which might inspire new approaches for the diagnosis, treatment and prevention of CRC on the basis of gut microbiota-derived metabolites SCFAs.

8.
Oxid Med Cell Longev ; 2021: 3328505, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34804363

RESUMO

Inflammaging refers to chronic, low-grade inflammation during aging, which contributes to the pathogenesis of age-related diseases. Studies have shown that probiotic intervention in the aging stage could delay aging-related disorders. However, whether the application of probiotics in early life could have antiaging effects on offspring was unknown. Here, we investigated the effects of Lactobacillus rhamnosus GG (LGG) colonization in early life on inflammaging of offspring. Pregnant mice with the same conception time were given LGG live bacteria (LC group) or LGG fixed bacteria (NC group) from the 18th day after pregnancy until natural birth. The progeny mice were treated with 107 cfu of live or fixed LGG for 0-5 days after birth, respectively. LGG colonization could be detected in the feces of 3-week offspring. The 16S rRNA sequencing analysis of 3-week-old offspring showed that colonization of LGG in early life could alter the composition and diversity of gut microbiota. Interestingly, the beneficial effects of LGG colonization in early life on the microbiota lasted to 8 months old. The abundance of longevity-related bacteria (Lactobacillus, Bifidobacterium, and Akkermansia muciniphila) increased significantly in the LGG colonization group. In addition, LGG colonization increased the abundance of short-chain fatty acid- (SCFA-) producing bacteria and the production of cecal SCFAs. LGG colonization in early life protected the intestinal barrier, enhanced antioxidant defense, attenuated epithelial cell DNA damage, and inhibited intestinal low-grade inflammation in 8-month-old progeny mice. Mechanically, LGG could upregulate Sirtuin1 (SIRT1)/Adenosine 5'-monophosphate-activated protein kinase (AMPK)/Peroxisome proliferator-activated receptor γ coactivator 1-α (PGC-1α) pathway and repress activation of nuclear factor-kappa B (NF-κB), while the protective effect of LGG was blunted after SIRT1 gene silencing. Together, LGG colonization in early life could ameliorate inflammaging of offspring, which would provide a new strategy for the prevention of age-related diseases.

10.
Front Oncol ; 11: 739648, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34733783

RESUMO

Accumulating evidence from studies in humans and animal models has elucidated that gut microbiota, acting as a complex ecosystem, contributes critically to colorectal cancer (CRC). The potential mechanisms often reported emphasize the vital role of carcinogenic activities of specific pathogens, but in fact, a series of metabolites produced from exogenous dietary substrates or endogenous host compounds occupy a decisive position similarly. Detrimental gut microbiota-derived metabolites such as trimethylamine-N-oxide, secondary bile acids, hydrogen sulfide and N-nitroso compounds could reconstruct the ecological composition and metabolic activity of intestinal microorganisms and formulate a microenvironment that opens susceptibility to carcinogenic stimuli. They are implicated in the occurrence, progression and metastasis of CRC through different mechanisms, including inducing inflammation and DNA damage, activating tumorigenic signaling pathways and regulating tumor immunity. In this review, we mainly summarized the intimate relationship between detrimental gut microbiota-derived metabolites and CRC, and updated the current knowledge about detrimental metabolites in CRC pathogenesis. Then, multiple interventions targeting these metabolites for CRC management were critically reviewed, including diet modulation, probiotics/prebiotics, fecal microbiota transplantation, as well as more precise measures such as engineered bacteria, phage therapy and chemopreventive drugs. A better understanding of the interplay between detrimental microbial metabolites and CRC would hold great promise against CRC.

11.
J Thorac Dis ; 13(9): 5448-5457, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34659811

RESUMO

Background: Total arch replacement (TAR) and frozen elephant trunk (FET) has been proposed as the primary arch repair method for acute type A aortic dissection (aTAAD). We introduce a modified "in situ" arch replacement with an integrative FET device for aTAAD. Methods: From January 2018 to December 2019, 507 aTAAD patients from Nanjing Drum Tower Hospital received surgical therapy; among them, 57 patients with modified island total arch replacement (MiTAR) and 138 patients with TAR were enrolled. Marfan syndrome, primary intimal tears located in the large curve of aortic arch +/- or supra-arch vessels and dilated aortic arch (≥45 mm) were contraindications for MiTAR. MiTAR involves two steps: first, insert a FET device into the descending aorta during the hypothermic circulation arrest period; second, anastomose the remaining "island" arch with the prosthetic vessel and the proximal part of the FET. Results: MiTAR patients were older than those receiving TAR (52.1 vs. 48.9 years; P=0.078), but their baseline demographics and manifestations of organ ischaemia were nearly the same. The times of cardiopulmonary bypass (CPB), aortic clamp and hypothermic circulation arrest were significantly shorter with MiTAR (209.3 vs. 267.1 minutes, P=0.000; 147.9 vs. 190.0 minutes, P=0.000; 34.0 vs. 39.4 minutes, P=0.003, respectively). The volumes of intraoperative transfusions of red blood cells (RBCs), fresh frozen plasma (FFP), platelets and cryoprecipitates were significantly lower in MiTAR (5.9 vs. 8.5 units, P=0.000; 758.3 vs. 930.4, P=0.000; 12.5 vs. 17.5 mL, P=0.000; 9.4 vs. 16.6 units, P=0.000). The 30-day mortality was 7.0% (4/57) for MiTAR and 11.6% (16/138) for TAR. One patient died and no patient received reintervention during the follow-up period, while the size of several levels of aorta showed a decreasing trend. Conclusions: MiTAR is a simplified approach to TAR that reduces the surgical trauma while achieving aortic reshaping effects.

12.
Biochim Biophys Acta Rev Cancer ; 1876(2): 188626, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34520804

RESUMO

The human body harbors a vast array of microbiota that modulates host pathophysiological processes and modifies the risk of diseases including cancer. With the advent of metagenomic sequencing studies, the intratumoural microbiota has been found as a component of the tumor microenvironment, imperceptibly affecting the tumor progression and response to current antitumor treatments. The underlying carcinogenic mechanisms of intratumoural microbiota, mainly including inducing DNA damages, activating oncogenic signaling pathways and suppressing the immune response, differ significantly in varied organs and are not fully understood. Some native or genetically engineered microbial species can specifically accumulate and replicate within tumors to initiate antitumor immunity, which will be conducive to pursue precise cancer therapies. In this review, we summarized the community characteristics and therapeutic potential of intratumoural microbiota across diverse tumor types. It may provide new insights for a better understanding of tumor biology and hint at the significance of manipulating intratumoural microbiota.


Assuntos
Microbiota/imunologia , Neoplasias/imunologia , Microambiente Tumoral/imunologia , Humanos
13.
Heart Surg Forum ; 24(4): E734-E740, 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34473021

RESUMO

BACKGROUND: Postoperative pneumonia (PP) is a complication after cardiac surgery. This study aimed to investigate the ability of procalcitonin (PCT) variation to diagnose postoperative pneumonia. METHOD: In this prospective observational study, patients with PP and age- and sex-matched cases in our center from October 10, 2020, to January 31, 2021, were included. Patients diagnosed with PP in this study met both clinical and microbiological diagnostic criteria. Blood samples were collected in all patients from the first postoperative day (POD1) to POD5 to measure PCT, white blood cells (WBCs), and C-reactive protein (CRP). PCT variation was calculated by the equation: (PCTdelayed - PCTPOD1)/PCTPOD1. The receiver operating characteristic and area under the curve (AUC) analyses were used to evaluate the diagnostic performance of different biomarkers. RESULTS: Our study enrolled 272 patients, including 24 patients with PP and 248 age- and sex-matched cases. From POD1 to POD5, the absolute value of PCT showed diagnostic significance for pneumonia (P < .05), WBC showed no differences, and CRP had no diagnostic value until POD4. Furthermore, PCT variation showed the best diagnostic value among those biomarkers (AUC 0.84, 95% confidence interval [CI] 0.71, 0.91). Multivariable logistic regression showed that PCT variation on POD2 had significant value to predict PP (odds ratio 5.602, 95% CI 2.178, 14.409, P < .01). CONCLUSION: Compared with PCT level, WBC count, and CRP level, PCT variation had the best diagnostic value in predicting PP.

14.
Nutrients ; 13(9)2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34579027

RESUMO

Inflammatory bowel disease (IBD) is a chronic, relapsing inflammatory disorder of the gastrointestinal tract, with increasing prevalence, and its pathogenesis remains unclear. Accumulating evidence suggested that gut microbiota and bile acids play pivotal roles in intestinal homeostasis and inflammation. Patients with IBD exhibit decreased microbial diversity and abnormal microbial composition marked by the depletion of phylum Firmicutes (including bacteria involved in bile acid metabolism) and the enrichment of phylum Proteobacteria. Dysbiosis leads to blocked bile acid transformation. Thus, the concentration of primary and conjugated bile acids is elevated at the expense of secondary bile acids in IBD. In turn, bile acids could modulate the microbial community. Gut dysbiosis and disturbed bile acids impair the gut barrier and immunity. Several therapies, such as diets, probiotics, prebiotics, engineered bacteria, fecal microbiota transplantation and ursodeoxycholic acid, may alleviate IBD by restoring gut microbiota and bile acids. Thus, the bile acid-gut microbiota axis is closely connected with IBD pathogenesis. Regulation of this axis may be a novel option for treating IBD.


Assuntos
Ácidos e Sais Biliares/fisiologia , Microbioma Gastrointestinal/fisiologia , Doenças Inflamatórias Intestinais/etiologia , Animais , Ácidos e Sais Biliares/metabolismo , Humanos
15.
J Cardiothorac Surg ; 16(1): 238, 2021 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-34425880

RESUMO

OBJECTIVE: Hyperbilirubinemia after cardiac surgery increases in-hospital mortality and is associated with poor prognosis. Our present study aimed to compare the efficacy of bilirubin adsorption (BA) and plasma exchange (PEX) in patients with hyperbilirubinemia after cardiac surgery. METHODS: We retrospectively included patients who underwent BA treatment or PEX treatment due to severe hyperbilirubinemia after cardiac surgery at our center from 2015 to 2020. We collected results from urine and liver function tests before and after treatment and compared the in-hospital mortality and morbidity between the two treatment groups. RESULTS: A total of 56 patients were enrolled in this study: 14 patients received BA treatment, and 42 patients received PEX treatment. Compared to the PEX group, the BA group exhibited a statistically significant reduction in total bilirubin (p = 0.016) and direct bilirubin (p = 0.036) levels. The in-hospital mortality was 85.7% (48/56) in the whole group, and the BA group had a lower mortality than the PEX group (71.4% vs. 90.5%, p = 0.078). The BA group showed better circulatory support, including lower risks of IABP (21.4% vs. 52.4%, p = 0.044), ECMO (21.4% vs. 50.0%, p = 0.061), reintubation (64.3% vs. 40.5%, p = 0.122) and ventricular arrhythmias (64.3% vs. 45.2%, p = 0.217). The in-hospital mortality was still lower in the BA treatment group than in the PEX treatment group (71.4% vs. 100%, p = 0.049) in the matched cohort. CONCLUSIONS: Compared to PEX treatment, BA treatment had a higher bilirubin removal ability in patients with hyperbilirubinemia and could reduce the mortality and risks of poor clinical outcomes. BA treatment should be considered an effective treatment method for patients with higher total bilirubin or direct bilirubin levels.


Assuntos
Bilirrubina , Procedimentos Cirúrgicos Cardíacos , Adsorção , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Humanos , Hiperbilirrubinemia/terapia , Troca Plasmática , Estudos Retrospectivos
16.
Front Cell Infect Microbiol ; 11: 679396, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34295835

RESUMO

As a class of the commonly used drugs in clinical practice, non-steroidal anti-inflammatory drugs (NSAIDs) can cause a series of adverse events including gastrointestinal injuries. Besides upper gastrointestinal injuries, NSAID enteropathy also attracts attention with the introduction of capsule endoscopy and double balloon enteroscopy. However, the pathogenesis of NSAID enteropathy remains to be entirely clarified. Growing evidence from basic and clinical studies presents that gut microbiota is a critical factor in NSAID enteropathy progress. We have reviewed the recent data about the interplay between gut microbiota dysbiosis and NSAID enteropathy. The chronic medication of NSAIDs could change the composition of the intestinal bacteria and aggravate bile acids cytotoxicity. Meanwhile, NSAIDs impair the intestinal barrier by inhibiting cyclooxygenase and destroying mitochondria. Subsequently, intestinal bacteria translocate into the mucosa, and then lipopolysaccharide released from gut microbiota combines to Toll-like receptor 4 and induce excessive production of nitric oxide and pro-inflammatory cytokines. Intestinal injuries present in the condition of intestinal inflammation and oxidative stress. In this paper, we also have reviewed the possible strategies of regulating gut microbiota for the management of NSAID enteropathy, including antibiotics, probiotics, prebiotics, mucosal protective agents, and fecal microbiota transplant, and we emphasized the adverse effects of proton pump inhibitors on NSAID enteropathy. Therefore, this review will provide new insights into a better understanding of gut microbiota in NSAID enteropathy.


Assuntos
Microbioma Gastrointestinal , Enteropatias , Microbiota , Probióticos , Anti-Inflamatórios não Esteroides/efeitos adversos , Humanos , Enteropatias/induzido quimicamente , Mucosa Intestinal
17.
J Card Surg ; 36(9): 3368-3370, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34124797

RESUMO

Ebstein's anomaly (EA) is a rare but difficult to manage congenital heart disease with a wide spectrum of clinical manifestations. We present a simplified repair method which combines the plication of the atrialized right ventricle, tricuspid leaflet repair and ring annuloplasty. This method is suitable for older adult EA patients with progressive right heart dysfunction symptoms. Compared with complex repair methods (such as Cone reconstruction) this simplified repair method can reduce surgical risk, and achieve mild or less tricuspid regurgitation with acceptable long-term effects compared with prosthetic valve replacement.


Assuntos
Anomalia de Ebstein , Insuficiência da Valva Tricúspide , Idoso , Anomalia de Ebstein/cirurgia , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/cirurgia , Humanos , Reoperação , Valva Tricúspide/diagnóstico por imagem , Valva Tricúspide/cirurgia , Insuficiência da Valva Tricúspide/cirurgia
18.
J Cell Mol Med ; 25(12): 5707-5720, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34002930

RESUMO

To investigate the therapeutic effects of phellodendrine in ulcerative colitis (UC) through the AMPK/mTOR pathway. Volunteers were recruited to observe the therapeutic effects of Compound Cortex Phellodendri Liquid (Huangbai liniment). The main components of Compound Cortex Phellodendri Liquid were analysed via network pharmacology. The target of phellodendrine was further analysed. Caco-2 cells were cultured, and H2 O2 was used to stimulate in vitro cell model. Expression levels of LC3, AMPK, p-AMPK, mTOR and p-mTOR were detected via Western blotting and through immunofluorescence experiments. The therapeutic effects of phellodendrine were analysed via expression spectrum chip sequencing. The sequencing of intestinal flora further elucidated the therapeutic effects of phellodendrine. Compared with the control group, Compound Cortex Phellodendri Liquid could substantially improve the healing of intestinal mucosa. Network pharmacology analysis revealed that phellodendrine is the main component of Compound Cortex Phellodendri Liquid. Moreover, this alkaloid targets the AMPK signalling pathway. Results of animal experiments showed that phellodendrine could reduce the intestinal damage of UC compared with the model group. Findings of cell experiments indicated that phellodendrine treatment could activate the p-AMPK /mTOR signalling pathway, as well as autophagy. Expression spectrum chip sequencing showed that treatment with phellodendrine could promote mucosal healing and reduce inflammatory responses. Results of intestinal flora detection demonstrated that treatment with phellodendrine could increase the abundance of flora and the content of beneficial bacteria. Phellodendrine may promote autophagy by regulating the AMPK-mTOR signalling pathway, thereby reducing intestinal injury due to UC.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Autofagia , Colite Ulcerativa/tratamento farmacológico , Regulação da Expressão Gênica/efeitos dos fármacos , Quinolizinas/farmacologia , Serina-Treonina Quinases TOR/metabolismo , Proteínas Quinases Ativadas por AMP/genética , Adulto , Animais , Estudos de Casos e Controles , Colite Ulcerativa/metabolismo , Colite Ulcerativa/patologia , Feminino , Humanos , Masculino , Camundongos Endogâmicos C57BL , Transdução de Sinais , Serina-Treonina Quinases TOR/genética
19.
J Card Surg ; 36(6): 1943-1952, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33870559

RESUMO

BACKGROUND: Preoperative malperfusion of acute type A aortic dissection (ATAAD) remains a catastrophic complication that is associated with high postoperative morbidity and mortality. The relationship between malperfusion and long-term survival in the Chinese population is unknown. METHODS: A total of 771 patients who underwent ATAAD surgery between January 2009 and December 2018 at our center were included. In-hospital mortality, complications, morbidity, and long-term survival were analyzed. RESULTS: Preoperative malperfusion was identified in 292 of 771 patients (37.9%), the in-hospital mortality rate was 20.9% in patients with preoperative malperfusion and 9.2% in those without. Independent predictors of in-hospital mortality included any malperfusion (odds ratio [OR], 5.132; p = .001), pericardial tamponade (OR, 1.808; p = .046), advanced age (OR, 1.028; p = .003), and cardiopulmonary bypass time (OR, 1.008; p = .001). Immediate emergency surgery (OR, 0.492; p = .007) and antegrade cerebral perfusion perioperatively (OR, 0.477; p = .020) were protective against postoperative mortality. The postoperative survival rates at 1, 3, and 5 years were 94.4% ± 1.5%, 91.9% ± 1.8%, and 83.0% ± 3.2% in patients with malperfusion and 94.7% ± 1.1%, 90.2% ± 1.7%, and 84.4% ± 2.7%, respectively, in those without. Preoperative malperfusion did not significantly affect the long-term outcomes of operative survivors (log-rank p = .601). CONCLUSION: Malperfusion resulted in an unfavorable prognosis in the short term, but showed almost equal long-term survival in patients without malperfusion of ATAAD. Emergency central repair might be considered to further improve the outcomes of ATAAD with malperfusion.


Assuntos
Aneurisma Dissecante , Aneurisma Aórtico , Doença Aguda , Aneurisma Dissecante/cirurgia , Aneurisma Aórtico/complicações , Aneurisma Aórtico/cirurgia , China/epidemiologia , Mortalidade Hospitalar , Humanos , Estudos Retrospectivos , Síndrome , Resultado do Tratamento
20.
mSystems ; 6(2)2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33727402

RESUMO

Early life events can lead to multiple diseases in adulthood. Previous studies suggested that polysorbate 80 (P80) as a widely used emulsifier in pharmaceutical formulations and food industries could impair the intestinal barrier. However, whether maternal P80 (MP80) exposure could affect the long-term health of offspring remains unknown. In this study, we found that maternal P80 intake could retard intestinal development, disrupt the intestinal barrier, and cause low-grade intestinal inflammation in 3-week-old offspring. 16S rRNA sequencing and correlation analysis revealed that Mucispirillum, Clostridium XI, and Parabacteroides, which positively correlated with intestinal proliferation and differentiation, were decreased in the maternal P80 group. Interestingly, the increase in some harmful bacteria, including Proteobacteria, Helicobacteraceae, Campylobacterales, and Desulfovibrionales, persisted from the weaning period to adulthood (3 to 8 weeks). Furthermore, a fecal microbiota transplantation assay showed that the mice gavaged with feces from 3-week-old offspring of the MP80 group presented more severe intestinal inflammation and barrier disruption than the mice that received feces from the offspring of the control group. Finally, maternal P80 intake remarkably aggravated the structural disorder of intestinal crypt, increased proinflammatory factors, and exacerbated dextran sulfate sodium (DSS)-induced colitis in adulthood. Conclusively, maternal P80 intake could induce gut dysbiosis and promote colitis susceptibility in adulthood. This study provides new insights into the prevention of inflammatory bowel disease (IBD).IMPORTANCE The main findings of this research showed that maternal P80 intake could disrupt the intestinal barrier, induce gut dysbiosis, and promote colitis susceptibility in adulthood. This study will enhance understanding of the prevention of IBD.

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