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1.
J Med Virol ; 95(1): e28267, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36319439

RESUMO

BACKGROUND: Myocardial injury is a major complication of sepsis and a key factor affecting prognosis. Therefore, early and accurate diagnosis and timely management of sepsis-induced cardiomyopathy (SICM) are of great significance for the prevention and treatment of sepsis. The gut microbiota has been shown to be closely associated with sepsis or myocardial injury, but the association between the gut microbiota and SICM is not fully understood. This study aimed to explore the link between gut microbiota composition and SICM. METHODS: A case-control and single-center study of clinical features and gut microbiota profiles by Metagenome and Virome was conducted in SICM patients (n = 15) and sepsis-uninduced cardiomyopathy patients (SNICM, n = 16). RESULTS: Compared with SNICM patients, SICM patients showed significant myocardial injury and higher 28-day mortality, SOFA scores, lactate levels, and infection levels on admission. Meanwhile, differences in the composition of gut bacteria, archaea, fungi, and viruses were analyzed between the two groups. Differential gut bacteria or viruses were found to have a good predictive effect on SICM. Furthermore, gut bacteria and viruses that differed between the two groups were strongly related. The abundance of Cronobacter and Cronobacter phage was higher in the SICM group than in the SNICM group, and the receiver operating characteristic curve showed that Cronobacter and Cronobacter phage both had a good predictive effect on SICM. CONCLUSIONS: SICM patients may have specific gut microbiota signatures, and Cronobacter and Cronobacter phages have a good ability to identify and diagnose SICM.


Assuntos
Bacteriófagos , Cardiomiopatias , Microbioma Gastrointestinal , Sepse , Humanos , Estudos de Casos e Controles , Disbiose/complicações , Cardiomiopatias/etiologia , Bactérias/genética , Sepse/complicações
2.
Zhongguo Zhong Yao Za Zhi ; 48(23): 6334-6346, 2023 Dec.
Artigo em Zh | MEDLINE | ID: mdl-38211990

RESUMO

Artemisiae Argyi Folium is commonly used in clinical practice. Artemisiae Verlotori Folium, the dried leaves of Artemisia verlotorum, is often used as a folk substitute for Artemisiae Argyi Folium in Lingnan area. In this study, gas chromatography-triple quadrupole mass spectrometry(GC-MS) was used to detect the volatile oil components of 27 samples of Artemisiae Verlotori Folium and 13 samples of Artemisiae Argyi Folium, and the volatile components were compared between the two species. The internal standard method was combined with multi-reaction monitoring mode(MRM) to determine the content of six major volatile components. Hierarchical clustering analysis(HCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA) were carried out for the content data. The results showed that the Artemisiae Argyi Folium samples had higher content and more abundant volatile oils than the Artemisiae Verlotori Folium samples. Artemisiae Argyi Folium mainly had the components with lower boiling points, while Artemisiae Verlotori Folium mainly had the components with higher boiling points. Terpenoids were the main volatile components in Artemisiae Verlotori Folium(mainly sesquiterpenoids) and Artemisiae Argyi Folium(monoterpenoids). In addition, Artemisiae Argyi Folium had higher content of oxygen-containing derivatives than Artemisiae Verlotori Folium. Furthermore, the stoichiometric analysis showed that the two species could be distinguished by both HCA and OPLS-DA, indicating that the volatile components of the two were significantly different. This study can provide a scientific basis for the quality evaluation and data support for the local rational application of Artemisiae Verlotori Folium in Lingnan.


Assuntos
Artemisia , Medicamentos de Ervas Chinesas , Óleos Voláteis , Cromatografia Gasosa-Espectrometria de Massas , Quimiometria , Folhas de Planta
3.
BMC Plant Biol ; 22(1): 285, 2022 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-35681138

RESUMO

Sweet potato (Ipomoea batatas [L.] Lam) is an important food crop, an excellent fodder crop, and a new type of industrial raw material crop. The lack of genomic resources could affect the process of industrialization of sweet potato. Few detailed reports have been completed on the mitochondrial genome of sweet potato. In this research, we sequenced and assembled the mitochondrial genome of sweet potato and investigated its substructure. The mitochondrial genome of sweet potato is 270,304 bp with 23 unique core genes and 12 variable genes. We detected 279 pairs of repeat sequences and found that three pairs of direct repeats could mediate the homologous recombination into four independent circular molecules. We identified 70 SSRs in the whole mitochondrial genome of sweet potato. The longest dispersed repeat in mitochondrial genome was a palindromic repeat with a length of 915 bp. The homologous fragments between the chloroplast and mitochondrial genome account for 7.35% of the mitochondrial genome. We also predicted 597 RNA editing sites and found that the rps3 gene was edited 54 times, which occurred most frequently. This study further demonstrates the existence of multiple conformations in sweet potato mitochondrial genomes and provides a theoretical basis for the evolution of higher plants and cytoplasmic male sterility breeding.


Assuntos
Genoma Mitocondrial , Ipomoea batatas , Cloroplastos/genética , Genes de Plantas , Genoma Mitocondrial/genética , Ipomoea batatas/genética , Melhoramento Vegetal
4.
Mediators Inflamm ; 2021: 5537966, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34434073

RESUMO

INTRODUCTION: In recent years, gamma-glutamyl transpeptidase to platelet ratio (GPR) has been proposed as a new inflammatory marker. We aimed to evaluate the association between GPR and outcomes after cardiac arrest (CA). METHODS: A total of 354 consecutive patients with CA were included in this retrospective study. Patients were divided into three groups according to tertiles of GPR (low, n = 119; middle, n = 117; and high, n = 118). To determine the relationship between GPR and prognosis, a logistic regression analysis was performed. The ability of GPR to predict the outcomes was evaluated by receiver operating characteristic (ROC) curve analysis. Two prediction models were established, and the likelihood ratio test (LRT) and the Akaike Information Criterion (AIC) were utilized for model comparison. RESULTS: Among the 354 patients (age 62 [52, 74], 254/354 male) who were finally included in the analysis, those in the high GPR group had poor outcomes. Multivariate logistic regression analysis revealed that GPR was independently associated with the three outcomes, for ICU mortality (odds ratios (OR) = 1.738, 95% confidence interval (CI): 1.221-2.474, P = 0.002), hospital mortality (OR = 1.676[1.164 - 2.413], P = 0.005), and unfavorable neurologic outcomes (OR = 1.623[1.121 - 2.351], P = 0.010). The area under the ROC curve was 0.611 (95% Cl: 0.558-0.662) for ICU mortality, 0.600 (95% CI: 0.547-0.651) for hospital mortality, and 0.602 (95% CI: 0.549-0.653) for unfavorable neurologic outcomes. Further, the LRT analysis showed that compared with the model without GPR, the GPR-combined model had a higher likelihood ratio χ 2 score and smaller AIC. CONCLUSION: GPR, as an inflammatory indicator, was independently associated with outcomes after CA. GPR is helpful in estimating the clinical outcomes of patients with CA.


Assuntos
Parada Cardíaca , gama-Glutamiltransferase , Feminino , Humanos , Cirrose Hepática , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Prognóstico , Curva ROC , Estudos Retrospectivos
5.
Biochem Biophys Res Commun ; 533(4): 1330-1337, 2020 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-33066957

RESUMO

Epithelial regeneration is essential for homeostasis and mucosal barrier repair. In this study, we aimed to define the effect of IL-10 on mucosal healing. Intestinal stem cells (ISCs) cultures and mice were treated with recombinant mice IL-10 (rmIL-10). The level of cell proliferation, differentiation, death and related signaling pathways for self-renewal of ISCs were measured in vitro and in vivo. It was uncovered that rmIL-10 increased the size and death, but reduced the total number of organoids. In addition, rmIL-10 depleted Lgr5+ ISCs and reduced epithelial proliferation, but enhanced the differentiation of epithelial cells and expanded numbers of transit-amplifying (TA) cells. These changes are related to the decrease of Wnt and Notch signals in vivo and in vitro. Meanwhile, increased expression of Paneth cells and decreased expression of enteroendocrine cells and goblet cells were induced by rmIL-10. Thus, our data indicate that IL-10 reduces the survival of Lgr5+ ISCs and proliferation of epithelial cells by inhibiting Notch and Wnt signaling, but promotes enhanced the differentiation of epithelial cells and expanded numbers of TA cells. Therefore, IL-10 acts as an anti-inflammatory factor, but may damage intestinal mucosa repair and maybe a potential target for the treatment of intestinal injury.


Assuntos
Interleucina-10/farmacologia , Mucosa Intestinal/citologia , Receptores Acoplados a Proteínas G/genética , Células-Tronco/citologia , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/genética , Autorrenovação Celular/efeitos dos fármacos , Células Enteroendócrinas/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Células Caliciformes/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Técnicas de Cultura de Órgãos , Celulas de Paneth/efeitos dos fármacos , Receptores Acoplados a Proteínas G/metabolismo , Receptores Notch/metabolismo , Proteínas Recombinantes/farmacologia , Células-Tronco/efeitos dos fármacos , Células-Tronco/metabolismo , Via de Sinalização Wnt/efeitos dos fármacos , Via de Sinalização Wnt/genética
6.
Addict Biol ; 25(3): e12755, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-30985062

RESUMO

N-Ethylpentylone (NEP) is one of the most confiscated synthetic cathinones in the world. However, its pharmacology and pharmacokinetics remain largely unknown. In this study, the pharmacokentics of NEP in rat nucleus accumbens (NAc) was assessed via brain microdialysis after the intraperitoneal (ip) administration of NEP (20 or 50 mg/kg). The concentrations of dopamine (DA) and serotonin (5-HT) and their metabolites, including 3,4-dihydroxyphenylacetic acid (DOPAC), 3-methoxytyramine (3-MT), and 5-hydroxyindoleacetic acid (5-HIAA), were simultaneously monitored to elucidate the pharmacological effect of NEP. In addition, the plasma levels of NEP were also assessed. The pharmacokinetics of NEP showed a dose-related pattern, with NEP rapidly passing through the blood-brain barrier and reaching a maximum concentration (Cmax ) at approximately 40-minutes postdose. Approximately 4% of plasma NEP was distributed to the NAc, and considering a homogeneous brain distribution, over 90% of plasma NEP was potentially distributed to the brain. High values of area under curve (AUC) and mean residence time (MRT) of NEP were observed in both the NAc and plasma, indicating large and long-lasting effects. NEP elicited dose-related increases in microdialysate DA and 5-HT and increased the concentration of 3-MT in a dose-related manner. However, the rate of DA converted into 3-MT was unaffected. NEP had a negative effect on the rates of which DA and 5-HT were transformed into DOPAC and 5-HIAA, respectively. In summary, NEP rapidly entered the NAc and showed a long-lasting effect. In addition, DA increased more significantly than 5-HT, indicating a large potential for NEP abuse.


Assuntos
Benzodioxóis/farmacologia , Butilaminas/farmacologia , Dopamina/metabolismo , Núcleo Accumbens/efeitos dos fármacos , Psicotrópicos/farmacologia , Serotonina/metabolismo , Ácido 3,4-Di-Hidroxifenilacético/metabolismo , Animais , Benzodioxóis/farmacocinética , Barreira Hematoencefálica/metabolismo , Butilaminas/farmacocinética , Cromatografia Líquida , Estado de Consciência , Dopamina/análogos & derivados , Relação Dose-Resposta a Droga , Ácido Hidroxi-Indolacético/metabolismo , Masculino , Microdiálise , Núcleo Accumbens/metabolismo , Psicotrópicos/farmacocinética , Ratos , Ratos Sprague-Dawley , Espectrometria de Massas em Tandem
7.
Behav Pharmacol ; 30(6): 500-505, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31033523

RESUMO

N-ethylpentylone (NEP), a new synthetic cathinone, has been rising to be one of the most popular cathinone derivatives in recent years. However, research on NEP is rather limited. In this study, locomotor stimulation and sensitization, as well as anxiety-like behavior induced by NEP were studied in Sprague-Dawley rats, using the open field and elevated plus maze respectively. Rats were administered NEP (5, 20 or 50 mg/kg, intraperitoneal), with saline as the negative control and methamphetamine (5 mg/kg) as a positive control. Acute administration of NEP at all the doses tested significantly promoted locomotor activity, presenting an inverted U-shaped dose-effect curve. The highest activity was observed at the 20 mg/kg dose group, with the average distance traveled 18 times higher than the saline group. Repeated administration of NEP enhanced locomotor activity only at the 5 mg/kg dose group. After a week's withdrawal, re-challenge of NEP failed to induce marked behavioral sensitization. In elevated plus maze experiments, both acute and repeated administration of 20 mg/kg NEP induced anxiolytic-like effects, while no significant alteration was observed in the 5 and 50 mg/kg dose groups. In summary, acute administration of NEP caused significantly enhanced locomotor activity in rats at all the tested doses, while repeated NEP administration enhanced locomotor activity only at a low dose (5 mg/kg), while a high dose (20 mg/kg) of NEP induced anxiolytic-like effects after both acute and repeated administration.


Assuntos
Ansiedade/tratamento farmacológico , Benzodioxóis/farmacologia , Butilaminas/farmacologia , Locomoção/efeitos dos fármacos , Alcaloides/metabolismo , Alcaloides/farmacologia , Animais , Ansiolíticos/farmacologia , Ansiedade/metabolismo , Comportamento Animal/efeitos dos fármacos , Benzodioxóis/metabolismo , Butilaminas/metabolismo , Masculino , Metanfetamina/farmacologia , Atividade Motora/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley
8.
Biomed Chromatogr ; 33(10): e4626, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31222753

RESUMO

N-Ethylpentylone (NEP) is a popular synthetic cathinone abused worldwide. To obtain more information about its pharmacokinetics and pharmacodynamics, a rapid, simple and sensitive liquid chromatography-tandem mass spectrometry method was developed for the determination of NEP, two important neurotransmitters, dopamine and serotonin, and their metabolites, including 3,4-dihydroxyphenylacetic acid, 3-methoxytyramine and 5-hydroxyindole-3-acetic acid, in rat brain microdialysate. The analytes were separated on a Phnomenex Polar C18 column, with a mobile phase of 0.1% formic acid in water (A) and 0.1% formic acid in acetonitrile (B) under gradient elution to shorten the total chromatographic run time. A triple quadruple mass spectrometer coupled with an electrospray ionization source in both positive and negative ion mode was used to detect the analytes. This method showed excellent accuracy (87.4-113.5%) and precision (relative standard deviation <15%) at three quality control levels. The limits of detection were 0.2 ng/mL for NEP and 0.2-50 nm for the others and good linearity was obtained. This study pioneered a method to integrate exogenous drugs and endogenous neurotransmitters as the drugs act on the same determination system, which means that this innovation can provide support for further study of the addictive effects of NEP or other synthetic cathinones on extracellular levels of dopamine and 5-hydroxytryptamine.


Assuntos
Benzodioxóis/análise , Butilaminas/análise , Cromatografia Líquida de Alta Pressão/métodos , Dopamina/análise , Núcleo Accumbens/química , Serotonina/análise , Animais , Benzodioxóis/administração & dosagem , Benzodioxóis/farmacocinética , Butilaminas/administração & dosagem , Butilaminas/farmacocinética , Dopamina/metabolismo , Limite de Detecção , Modelos Lineares , Microdiálise , Núcleo Accumbens/metabolismo , Ratos , Reprodutibilidade dos Testes , Serotonina/metabolismo , Espectrometria de Massas em Tandem/métodos
9.
Exp Cell Res ; 359(2): 441-448, 2017 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-28830684

RESUMO

Stress-induced cardiomyocyte apoptosis contributes to the pathogenesis of a variety of cardiovascular diseases, but how stress induces cardiomyocyte apoptosis remains largely unclear. The present study aims to investigate the effects of Axin1 up-regulated 1 (Axud1), a novel pro-apoptotic protein, on the cardiomyocyte survival and the underlying mechanisms. To this end, a rat model under restraint stress (RS) was established and in vitro stress-induced cardiomyocytes culture was achieved. Our data showed that Axud1 was upregulated in the rat myocardia after exposure to RS. Anti-apoptotic Bcl-2 was decreased, whereas pro-apoptotic Bax and Cleaved caspase-3 (Cc3) were increased in a time-dependent manner. The Wnt/ß-catenin signaling was observed to be interestingly activated in heart undergoing RS. In addition, the treatment of norepinephrine (NE) to in vitro cardiomyocytes increased Axud1 level and induced cell apoptosis. Wnt/ß-catenin signaling was consistently activated. Knockdown of Axud1 using specific siRNA blunted NE-induced cardiomyocytes apoptosis and also inactivated the Wnt/ß-catenin signaling. XAV-939, an inhibitor of Wnt/ß-catenin signaling, partially reversed the pro-apoptotic effect of NE. In conclusion, Axud1 accelerated stress-induced cardiomyocytes apoptosis through activation of Wnt/ß-catenin signaling pathway. Our data provided novel evidence that therapeutic strategies against Axud1 or Wnt/ß-catenin signaling might be promising in relation to RS-induced myocardial injury.


Assuntos
Proteínas Reguladoras de Apoptose/genética , Miócitos Cardíacos/metabolismo , Estresse Psicológico/genética , Fatores de Transcrição/genética , Via de Sinalização Wnt , beta Catenina/genética , Animais , Apoptose , Proteínas Reguladoras de Apoptose/antagonistas & inibidores , Proteínas Reguladoras de Apoptose/metabolismo , Caspase 3/genética , Caspase 3/metabolismo , Linhagem Celular , Regulação da Expressão Gênica , Compostos Heterocíclicos com 3 Anéis/farmacologia , Imobilização , Masculino , Camundongos , Miocárdio/metabolismo , Miocárdio/patologia , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/patologia , Norepinefrina/antagonistas & inibidores , Norepinefrina/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Ratos , Ratos Sprague-Dawley , Estresse Psicológico/metabolismo , Estresse Psicológico/fisiopatologia , Fatores de Transcrição/antagonistas & inibidores , Fatores de Transcrição/metabolismo , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo , beta Catenina/metabolismo
10.
Inorg Chem ; 54(23): 11299-306, 2015 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-26561233

RESUMO

Currently, the development of efficient red-emitting persistent phosphor is still an ongoing challenge. Herein, a novel red-emitting LPL phosphor Ca3Ti2O7:Pr(3+) is successfully prepared by a high-temperature solid-state method. XRD Rietveld refinement analyses demonstrate the high phase purity of the sample which crystallizes in an orthorhombic Ccm21 space group with lattice parameters of a = 5.7702(5) Å, b = 19.4829(7) Å, and c = 5.1214(2) Å. Electronic structure of the host matrix is analyzed by the first-principle calculation using CASTEP code. The calculation results show that Ca3Ti2O7 has a direct band gap with CB and VB mainly composed of the Ti-3d and O-2p states, respectively. On the basis of the DR spectrum, the band gap is determined to be 3.6 eV. It is demonstrated that the 612 nm red-emitting persistent luminescence of Ca3Ti2O7:Pr(3+) can be either activated by Ti(4+)-O(2-) → Ti(3+)-O(-) host absorption and Pr(3+)-O-Ti(4+) → Pr(4+)-O-Ti(3+) IVCT in the UV region, or Pr(3+):(3)H4 → (3)PJ transition in the blue region. The red afterglow can last for ∼ 5 min observed by the naked eyes in the dark after ceasing the irradiation source. On the basis of the TL analyses, the trap is found exponentially distributed in the host with the depth of 0.69-0.92 eV. Finally, a possible LPL mechanism for Ca3Ti2O7:Pr(3+) is proposed.

11.
Front Med (Lausanne) ; 11: 1396254, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38835803

RESUMO

Objectives: The association between vitamin D and blood pressure in elderly patients with hypertension complicated by osteoporosis remains unclear. The objective of this study is to explore whether vitamin D deficiency contributes to elevated blood pressure in elderly individuals with both hypertension and osteoporosis. Methods: This study represents a single-center retrospective observational investigation carried out at the Zhongshan Hospital Affiliated to Xiamen University. Ambulatory blood pressure, bone density, vitamin D levels, and additional laboratory parameters were collected upon admission. The association between vitamin D and ambulatory blood pressure outcomes was assessed using Spearman correlation tests and partial correlation analyses. The relationship between vitamin D and changes in blood pressure was analyzed through Generalized Additive Models, and threshold analysis was conducted to explore potential thresholds. Results: 139 patients with newly diagnosed osteoporosis were consecutively included (mean age 73 years, 84.9% female). There is a negative correlation between 25-(OH) D3 and 24 h mean systolic blood pressure (mSBP), diurnal mSBP, nocturnal mSBP, maximum SBP, respectively. The results of the generalized additive model analysis show that there is a nonlinear relationship between 25-(OH) D3 and 24 h mSBP, diurnal mSBP, nocturnal mSBP, respectively. After determining the critical point of 25-(OH) D3 as 42 nmol/L, a segmented linear regression model was used to calculate the effect size and 95% confidence interval on both sides of the critical point. When 25-(OH) D3 is ≤42 nmol/L, it significantly negatively correlates with 24 h, diurnal, and nocturnal mean SBP. Conversely, when 25-(OH) D3 exceeds 42 nmol/L, there is no statistically significant association with 24 h, diurnal, or nocturnal mSBP. Conclusion: There was a significant negative correlation between vitamin D levels and blood pressure levels in elderly patients with hypertension and osteoporosis.

12.
IEEE Trans Image Process ; 32: 2003-2016, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35839180

RESUMO

Typical methods for pedestrian detection focus on either tackling mutual occlusions between crowded pedestrians, or dealing with the various scales of pedestrians. Detecting pedestrians with substantial appearance diversities such as different pedestrian silhouettes, different viewpoints or different dressing, remains a crucial challenge. Instead of learning each of these diverse pedestrian appearance features individually as most existing methods do, we propose to perform contrastive learning to guide the feature learning in such a way that the semantic distance between pedestrians with different appearances in the learned feature space is minimized to eliminate the appearance diversities, whilst the distance between pedestrians and background is maximized. To facilitate the efficiency and effectiveness of contrastive learning, we construct an exemplar dictionary with representative pedestrian appearances as prior knowledge to construct effective contrastive training pairs and thus guide contrastive learning. Besides, the constructed exemplar dictionary is further leveraged to evaluate the quality of pedestrian proposals during inference by measuring the semantic distance between the proposal and the exemplar dictionary. Extensive experiments on both daytime and nighttime pedestrian detection validate the effectiveness of the proposed method.

13.
Nat Commun ; 14(1): 6779, 2023 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-37880227

RESUMO

Intestinal organoid transplantation is a promising therapy for the treatment of mucosal injury. However, how the transplanted organoids regulate the immune microenvironment of recipient mice and their role in treating intestinal ischemia-reperfusion (I/R) injury remains unclear. Here, we establish a method for transplanting intestinal organoids into intestinal I/R mice. We find that transplantation improve mouse survival, promote self-renewal of intestinal stem cells and regulate the immune microenvironment after intestinal I/R, depending on the enhanced ability of macrophages polarized to an anti-inflammatory M2 phenotype. Specifically, we report that L-Malic acid (MA) is highly expressed and enriched in the organoids-derived conditioned medium and cecal contents of transplanted mice, demonstrating that organoids secrete MA during engraftment. Both in vivo and in vitro experiments demonstrate that MA induces M2 macrophage polarization and restores interleukin-10 levels in a SOCS2-dependent manner. This study provides a therapeutic strategy for intestinal I/R injury.


Assuntos
Macrófagos , Traumatismo por Reperfusão , Camundongos , Animais , Organoides/transplante , Isquemia/terapia
14.
Cell Rep Med ; 4(3): 100979, 2023 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-36948152

RESUMO

There are significant differences in the susceptibility of populations to intestinal ischemia/reperfusion (I/R), but the underlying mechanisms remain elusive. Here, we show that mice exhibit significant differences in susceptibility to I/R-induced enterogenic sepsis. Notably, the milnacipran (MC) content in the enterogenic-sepsis-tolerant mice is significantly higher. We also reveal that the pre-operative fecal MC content in cardiopulmonary bypass patients, including those with intestinal I/R injury, is associated with susceptibility to post-operative gastrointestinal injury. We reveal that MC attenuates mouse I/R injury in wild-type mice but not in intestinal epithelial aryl hydrocarbon receptor (AHR) gene conditional knockout mice (AHRflox/flox) or IL-22 gene deletion mice (IL-22-/-). Collectively, our results suggest that gut microbiota affects susceptibility to I/R-induced enterogenic sepsis and that gut microbiota-derived MC plays a pivotal role in tolerance to intestinal I/R in an AHR/ILC3/IL-22 signaling-dependent manner, revealing the pathological mechanism, potential prevention and treatment drugs, and treatment strategies for intestinal I/R.


Assuntos
Microbioma Gastrointestinal , Traumatismo por Reperfusão , Camundongos , Animais , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/patologia , Transdução de Sinais , Camundongos Knockout , Isquemia
15.
Nat Commun ; 14(1): 5437, 2023 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-37673874

RESUMO

Intestinal ischemia/reperfusion (I/R) injury is a severe clinical condition without optimal diagnostic markers nor clear molecular etiological insights. Plasma exosomal circular RNAs (circRNAs) are valuable biomarkers and therapeutic targets for various diseases, but their role in intestinal I/R injury remains unknown. Here we screen the expression profile of circRNAs in intestinal tissue exosomes collected from intestinal I/R mice and identify circEZH2_005 as a significantly downregulated exosomal circRNA. In parallel, circEZH2_005 is also reduced in the plasma of clinical cardiac surgery patients who developed postoperative intestinal I/R injury. Exosomal circEZH2_005 displays a significant diagnostic value for intestinal injury induced by I/R. Mechanistically, circEZH2_005 is highly expressed in intestinal crypt cells. CircEZH2_005 upregulation promotes the proliferation of Lgr5+ stem cells by direct interaction with hnRNPA1, and enhanced Gprc5a stability, thereby alleviating I/R-induced intestinal mucosal damage. Hence, exosomal circEZH2_005 may serve as a biomarker for intestinal I/R injury and targeting the circEZH2_005/hnRNPA1/Gprc5a axis may be a potential therapeutic strategy for intestinal I/R injury.


Assuntos
RNA Circular , Traumatismo por Reperfusão , Animais , Camundongos , RNA Circular/genética , Transdução de Sinais , Biomarcadores , Traumatismo por Reperfusão/genética , Isquemia
16.
ESC Heart Fail ; 9(2): 1360-1369, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35146943

RESUMO

AIMS: Chronic heart failure (CHF) is often a common comorbidity in critically ill patients admitted to the intensive care unit (ICU) and carries an extremely poor prognosis. The study aimed to investigate the relationship between the blood urea nitrogen to serum albumin ratio (BAR) and the prognosis of patients with CHF admitted to the ICU. METHODS AND RESULTS: This retrospective cohort study included 1545 critically ill patients with CHF as a diagnosed comorbidity admitted to the ICU deposited in the MIMIC-III database, of whom 90 day all-cause mortality was 27.6% (n = 427) and in-hospital mortality was 17.3% (n = 267). The results of multiple logistic regression analysis indicated that BAR is an independent risk factor for in-hospital mortality in critically ill patients with CHF [compared with BAR ≤ 0.83; 0.83 < BAR ≤ 1.24: odds ratio (OR) 2.647, 95% confidence interval (CI) 1.797-3.900, P < 0.001; BAR ≥ 1.24: OR 3.628, 95% CI 2.604-5.057, P < 0.001]. Multiple COX regression analysis found a relationship between BAR and all-cause mortality at 90 day follow-up (0.83 < BAR ≤ 1.24: OR 1.948, 95% CI 1.259-3.014, P < 0.003; BAR ≥ 1.24: OR 1.807, 95% CI 1.154-2.830, P < 0.01; BAR ≤ 0.83 as a reference). Kaplan-Meier curves also showed similar results as well (P < 0.001). The areas under the receiver operating characteristic curves for predicting in-hospital mortality and 90 day all-cause mortality were 0.622 and 0.647, respectively. CONCLUSIONS: BAR is an independent risk factor for in-hospital mortality and 90 day mortality in critically ill patients with CHF admitted to the ICU.


Assuntos
Insuficiência Cardíaca , Albumina Sérica , Nitrogênio da Ureia Sanguínea , Humanos , Prognóstico , Estudos Retrospectivos
17.
Front Cardiovasc Med ; 9: 985503, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36035923

RESUMO

Objectives: The relationship between the MELD-XI score, a modified version of the MELD score, and the long-term prognosis of hospitalized patients with chronic heart failure is unclear. The aim of this study was to determine the long-term prognostic relationship of MELD-XI score in patients with chronic heart failure. Methods: This is a retrospective cohort study of patients with chronic heart failure who were initially hospitalized in the Second Affiliated Hospital of Chongqing Medical University from February 2017 to December 2017. The primary clinical outcome was all-cause mortality within 3 years. Cox regression and lasso regression were used to screen variables and build a prognostic model. Combined with the MELD-XI score, the final model was adjusted, and the predictive ability of the model was evaluated. Survival curves were estimated using the Kaplan-Meier method and compared by the log rank test. Results: A total of 400 patients with chronic heart failure were included (median age 76 years, 51.5% female). During the 3-year follow-up period, there were 97 all-cause deaths, including 63 cardiac deaths. Six characteristic variables (NT-proBNP, BUN, RDW CV, Na+ and prealbumin) were selected by univariate Cox regression and lasso regression. Survival analysis results showed that elevated MELD-XI score at baseline predicted the risk of all-cause mortality at 3 years in patients (HR 3.19, 95% CI 2.11-4.82, P < 0.001; HRadjusted 1.79, 95% CI 1.09-2.92, P = 0.020). Subgroup analysis showed that MELD-XI score still had prognostic value in the subgroup without chronic kidney disease (HR 3.30 95%CI 2.01-5.42 P < 0.001; HRadjusted 1.88 95%CI 1.06-3.35 P = 0.032, P for interaction = 0.038). Conclusions: This study proved that the MELD-XI score at admission was related to the poor prognosis of hospitalized patients with chronic heart failure within 3 years.

18.
Medicine (Baltimore) ; 101(47): e32050, 2022 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-36451499

RESUMO

BACKGROUD: Neonatal pericardial effusion (PCE) is one of the most severe complications of central catheters in neonates with its rapid progression and high mortality. We aim to estimate the overall incidence and mortality of catheter-related neonatal PCE, more importantly, to identify possible predictors for clinical reference. METHODS: We searched MEDLINE, Embase, Cochrane Library, Web of Science, china national knowledge infrastructure, Wanfang Data, and Sinomed databases for subject words "central catheter," "neonate," "pericardial effusion" and their random words till June 8, 2020. This meta-analysis is based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Possible predictors of occurrences and deaths were extracted and assessed cooperatively. The pooled incidence rate of catheter-related neonatal PCE was calculated using a random effects model. RESULTS: Twenty-one cohort studies and 99 cases were eligible. Pooled incidence is 3·8‰[2.2‰, 6.7‰]. Polyurethane catheters generate significantly more neonatal PCE than silicone counterparts (P < .01). 27% of the patients die. The mortality of patients with bradycardia is higher than others (P < .05). Catheters with a guidewire result in more deaths than umbilical venous catheter (UVC) and peripherally inserted central catheters (PICC) (P < .05). Without pericardiocentesis, mortality increases (P < .01). The difference of deaths between reposition and removing the catheter is insignificant (P > .05). CONCLUSION: Central catheters in Seldinger Technique (with a guidewire) put neonates at greater risk of PCE and consequent death. Silicone catheters excel at avoiding deadly catheter-related PCE, which could be a better choice in neonatal intensive care units (NICU). When catheter-related PCE occurs, timely diagnosis and pericardiocentesis save lives.


Assuntos
Catéteres , Derrame Pericárdico , Recém-Nascido , Humanos , Incidência , Pericardiocentese , Derrame Pericárdico/epidemiologia , Derrame Pericárdico/etiologia , Silicones
19.
Int J Biol Sci ; 18(10): 3981-3992, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35844797

RESUMO

Intestinal ischemia/reperfusion (I/R) is a common pathophysiological process in clinical severe patients, and the effect of intestinal I/R injury on the patient's systemic pathophysiological state is far greater than that of primary intestinal injury. In recent years, more and more evidence has shown that intestinal microbiota and its metabolites play an important role in the occurrence, development, diagnosis and treatment of intestinal I/R injury. Intestinal microbiota is regulated by host genes, immune response, diet, drugs and other factors. The metabolism and immune potential of intestinal microbiota determine its important significance in host health and diseases. Therefore, targeting the intestinal microbiota and its metabolites may be an effective therapy for the treatment of intestinal I/R injury and intestinal I/R-induced extraintestinal organ injury. This review focuses on the role of intestinal microbiota and its metabolites in intestinal I/R injury and intestinal I/R-induced extraintestinal organ injury, and summarizes the latest progress in regulating intestinal microbiota to treat intestinal I/R injury and intestinal I/R-induced extraintestinal organ injury.


Assuntos
Microbioma Gastrointestinal , Traumatismo por Reperfusão , Humanos , Intestinos , Traumatismo por Reperfusão/metabolismo
20.
Microbiome ; 10(1): 38, 2022 03 03.
Artigo em Inglês | MEDLINE | ID: mdl-35241180

RESUMO

BACKGROUND: Intestinal ischemia/reperfusion (I/R) injury has high morbidity and mortality rates. Gut microbiota is a potential key factor affecting intestinal I/R injury. Populations exhibit different sensitivities to intestinal I/R injury; however, whether this interpopulation difference is related to variation in gut microbiota is unclear. Here, to elucidate the interaction between the gut microbiome and intestinal I/R injury, we performed 16S DNA sequencing on the preoperative feces of C57BL/6 mice and fecal microbiota transplantation (FMT) experiments in germ-free mice. The transwell co-culture system of small intestinal organoids extracted from control mice and macrophages extracted from control mice or Toll-like receptor 2 (TLR2)-deficient mice or interleukin-10 (IL-10)-deficient mice were established separately to explore the potential mechanism of reducing intestinal I/R injury. RESULTS: Intestinal I/R-sensitive (Sen) and intestinal I/R-resistant (Res) mice were first defined according to different survival outcomes of mice suffering from intestinal I/R. Fecal microbiota composition and diversity prior to intestinal ischemia differed between Sen and Res mice. The relative abundance of Lactobacillus murinus (L. murinus) at the species level was drastically higher in Res than that in Sen mice. Clinically, the abundance of L. murinus in preoperative feces of patients undergoing cardiopulmonary bypass surgery was closely related to the degree of intestinal I/R injury after surgery. Treatment with L. murinus significantly prevented intestinal I/R-induced intestinal injury and improved mouse survival, which depended on macrophages involvement. Further, in vitro experiments indicated that promoting the release of IL-10 from macrophages through TLR2 may be a potential mechanism for L. murinus to reduce intestinal I/R injury. CONCLUSION: The gut microbiome is involved in the postoperative outcome of intestinal I/R. Lactobacillus murinus alleviates mice intestinal I/R injury through macrophages, and promoting the release of IL-10 from macrophages through TLR2 may be a potential mechanism for L. murinus to reduce intestinal I/R injury. This study revealed a novel mechanism of intestinal I/R injury and a new therapeutic strategy for clinical practice. Video Abstract.


Assuntos
Traumatismo por Reperfusão , Receptor 2 Toll-Like , Animais , Humanos , Interleucina-10 , Isquemia , Lactobacillus , Macrófagos , Camundongos , Camundongos Endogâmicos C57BL , Traumatismo por Reperfusão/tratamento farmacológico
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