RESUMEN
Transition metal-peroxide complexes play a crucial role as intermediates in oxidation reactions. To unravel the mechanism of benzaldehyde oxidation by the Co-peroxo complex, we conducted density functional theory (DFT) calculations. The identified competing mechanisms include nucleophilic attack and hydrogen atom transfer (HAT). The nucleophilic attack pathway involves Co-O cleavage and nucleophilic attack, leading to the formation of the benzoate product. And the HAT pathway comprises O-O cleavage and HAT, ultimately resulting in the benzoate product. DFT calculations revealed that the formation of the end-on Co-superoxo complex 2 through Co-O cleavage, starting from the side-on Co-peroxo complex 1, is much more favorable than the formation of the two-terminal oxyl-radical intermediate 3 through O-O cleavage. Compared with the nucleophilic attack of benzaldehyde by 2, the abstraction of a hydrogen atom from benzaldehyde by 3 requires higher energy. The nature of the nucleophilicity of 2 and 3 accounts for the reactivity of the reaction.
RESUMEN
We have developed a lanthanide/B(C6F5)3-promoted hydroboration reduction of indoles and quinolines with pinacolborane (HBpin). This reaction provides streamlined access to a range of nitrogen-containing compounds in moderate to excellent yields. Large-scale synthesis and further transformations to bioactive compounds indicate that the method has potential practical applications. Preliminary mechanistic studies suggest that amine additives promote the formation of indole-borane intermediates, and the lanthanide/B(C6F5)3-promoted hydroboration reduction proceeds via hydroboration of indole-borane intermediates with HBpin and in situ-formed BH3 species, followed by the protodeborylation process.
RESUMEN
Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract which is mediated by the inappropriate immune responses. This study was aimed to identify novel diagnostic biomarkers for diagnosis of IBD and explore the relationship between the diagnostic biomarkers and infiltrated immune cells. GSE38713, GSE53306, and GSE75214 downloaded from the Gene Expression Omnibus (GEO) database were split into training and testing sets. Differentially expressed genes (DEGs) were screened using the "limma" package. Gene Ontology (GO) and KEGG pathway enrichment analysis of DEGs were performed by clusterProfiler package. The LASSO regression and support vector machine recursive feature elimination (SVM-RFE) algorithms were conducted to identify novel diagnostic biomarkers. The receiver operating characteristic (ROC) curve was applied to evaluate the diagnostic value of the candidate biomarkers. The relationship of the candidate biomarkers and infiltrating immune cells in IBD were evaluated by CIBERSOTR. Quantitative Real-Time PCR (qRT-PCR) was applied to measure the expression level of the biomarkers in IBD. A total of 289 dysregulated genes were identified as DEGs in IBD. These DEGs were significantly enriched in chemokine signaling pathway and cytokine-cytokine receptor interaction. RHOU was identified as a critical diagnostic gene in IBD, which was confirmed using ROC curve and qRT-PCR assays. Immune cell infiltration analysis showed that RHOU was correlated with macrophages M2, dendritic cells resting, mast cells resting, T cells CD4 memory resting, macrophages M0, and mast cells activated. Our results imply that RHOU may be a potential diagnostic biomarker for IBD.
Asunto(s)
Enfermedades Inflamatorias del Intestino , Humanos , Enfermedades Inflamatorias del Intestino/diagnóstico , Enfermedades Inflamatorias del Intestino/genética , Aprendizaje Automático , Biología Computacional , Citocinas , BiomarcadoresRESUMEN
Early bolting of Peucedanum praeruptorum Dunn severely affects its quality. In this study, we compared with the root structure of P. praeruptorum and its four coumarins content between early bolting (CT) and unbolting (WT) at different growth stages. We found that the proportion of area outside the root cambium (Rs) was higher in the WT plants than in the CT plants and correlated positively with the proximity to the root tip. Furthermore, the content of all four coumarins was also higher in the WT plants relative to the CT plants. In addition, we identified 15,524 differentially expressed genes (DEGs) between the two plant varieties. 11 DEGs are involved in the photoperiod and gibberellin pathways that regulate early bolting and 24 genes involved in coumarins biosynthesis were also identified. Nevertheless, early bolting of P. praeruptorum does affect its quality formation, and further studies are needed to confirm its mechanism.
Asunto(s)
Apiaceae , Cumarinas , Cumarinas/química , Apiaceae/genética , Apiaceae/química , Apiaceae/metabolismoRESUMEN
Over the past decade, immune checkpoint inhibitors (ICIs) have emerged as a revolutionary cancer treatment modality, offering long-lasting responses and survival benefits for a substantial number of cancer patients. However, the response rates to ICIs vary significantly among individuals and cancer types, with a notable proportion of patients exhibiting resistance or showing no response. Therefore, dual ICI combination therapy has been proposed as a potential strategy to address these challenges. One of the targets is TIGIT, an inhibitory receptor associated with T-cell exhaustion. TIGIT has diverse immunosuppressive effects on the cancer immunity cycle, including the inhibition of natural killer cell effector function, suppression of dendritic cell maturation, promotion of macrophage polarization to the M2 phenotype, and differentiation of T cells to regulatory T cells. Furthermore, TIGIT is linked with PD-1 expression, and it can synergize with PD-1/PD-L1 blockade to enhance tumor rejection. Preclinical studies have demonstrated the potential benefits of co-inhibition of TIGIT and PD-1/PD-L1 in enhancing anti-tumor immunity and improving treatment outcomes in several cancer types. Several clinical trials are underway to evaluate the safety and efficacy of TIGIT and PD-1/PD-L1 co-inhibition in various cancer types, and the results are awaited. This review provides an overview of the mechanisms of TIGIT and PD-1/PD-L1 co-inhibition in anti-tumor treatment, summarizes the latest clinical trials investigating this combination therapy, and discusses its prospects. Overall, co-inhibition of TIGIT and PD-1/PD-L1 represents a promising therapeutic approach for cancer treatment that has the potential to improve the outcomes of cancer patients treated with ICIs.
Asunto(s)
Neoplasias , Receptor de Muerte Celular Programada 1 , Humanos , Antígeno B7-H1 , Neoplasias/tratamiento farmacológico , Inmunoterapia/métodos , Terapia Combinada , Receptores InmunológicosRESUMEN
Hepatic stellate cell (HSC) activation is a critical event in the development of hepatic fibrosis and hepatocellular carcinoma (HCC). By the release of soluble cytokines, chemokines, and chemotaxis, HSCs affect HCC cell phenotypes through a complex tumor microenvironment. In this study, weighted gene co-expression network analysis (WGCNA) was used to identify the TGF-ß signaling pathway as a key signaling pathway in Hep3B cells cultured in HSC conditioned medium. MIR4435-2HG is a hub lncRNA associated with the TGF-ß signaling pathway and HSC activation. HSC-condition medium (CM) culture induced HCC cell malignant behaviors, which were partially reversed by MIR4435-2HG silencing. miR-506-3p directly bound to MIR4435-2HG and the 3'UTR of TGFB1. Similarly, overexpression of miR-506-3p also attenuated HSC-CM-induced malignant behavior of HCC cells. In HSC-CM cultured HCC cells, the effects of MIR4435-2HG knockdown on TGFB1 expression and HCC cell phenotypes were partially reversed by miR-506-3p inhibition. HSCs affected HCC cell phenotypes by releasing CXCL1. In an orthotopic xenotransplanted tumor model of HCC cells plus HSCs in mice, CXCR2 knockdown in HCC cells significantly inhibited tumorigenesis, which was partially reversed by MIR4435-2HG overexpression in HCC cells. In HCC tissue samples, the levels of CXCL1, TGF-ß1, and MIR4435-2HG were upregulated, while miR-506-3p expression was downregulated. In conclusion, HSC-released CXCL1 aggravated HCC cell malignant behaviors through the MIR4435-2HG/miR-506-3p/TGFB1 axis. In addition to CXCL1, the MIR4435-2HG/miR-506-3p/TGFB1 axis might also be the underlying target for HCC therapy.
Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroARNs , ARN Largo no Codificante , Animales , Ratones , Carcinoma Hepatocelular/patología , MicroARNs/metabolismo , Células Estrelladas Hepáticas/metabolismo , Factor de Crecimiento Transformador beta1/genética , Factor de Crecimiento Transformador beta1/metabolismo , Neoplasias Hepáticas/patología , Proliferación Celular/genética , ARN Largo no Codificante/genética , Microambiente TumoralRESUMEN
Recent evidence has shown that immune checkpoint inhibitors (ICIs) are efficacious for treating brain metastases of various primary tumors. However, the immunosuppressive tumor microenvironment and the blood-brain barrier (BBB) or blood-tumor barrier (BTB) essentially restrict the efficacy of ICIs. Stereotactic radiosurgery (SRS) can be a powerful ally to ICIs due to its trait of disrupting the BBB/BTB and increasing the immunogenicity of brain metastases. The combination of SRS + ICI has shown synergy in brain metastases in several retrospective studies. Nevertheless, the optimal schedule for the combination of SRS and ICI in brain metastases is yet to be determined. In this review, we summarized the current clinical and preclinical evidence on the timing and sequence of SRS + ICI to provide insight into the current state of knowledge about this important area in patient care.
Asunto(s)
Neoplasias Encefálicas , Radiocirugia , Humanos , Inhibidores de Puntos de Control Inmunológico , Estudios Retrospectivos , Neoplasias Encefálicas/patología , Inmunosupresores , Microambiente TumoralRESUMEN
BACKGROUND: Alcohol-associated liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) are two of the most common etiologies of chronic liver disease worldwide. Changes in intestinal permeability and increased gut microbial translocation have been posited as important contributors to inflammation in both ALD and NAFLD. However, gut microbial translocation has not been compared between the two etiologies and can lead to better understanding of the differences in their pathogenesis to liver disease. METHODS: We compared serum and liver markers in the following five models of liver disease to understand the differences in the role of gut microbial translocation on liver disease progression caused by ethanol versus Western diet: (1) 8-week chronic ethanol feeding model. (2) 2-week chronic-plus-binge (National Institute on Alcohol Abuse and Alcoholism (NIAAA)) ethanol feeding model. (3) 2-week chronic-plus-binge (NIAAA) ethanol feeding model in microbiota-humanized gnotobiotic mice colonized with stool from patients with alcohol-associated hepatitis. (4) 20-week Western-diet-feeding model of NASH. (5) 20-week Western-diet-feeding model in microbiota-humanized gnotobiotic mice colonized with stool from NASH patients. RESULTS: Translocation of bacterial lipopolysaccharide to the peripheral circulation was seen in both ethanol-induced and diet-induced liver disease, but translocation of bacteria itself was restricted to only ethanol-induced liver disease. Moreover, the diet-induced steatohepatitis models developed more significant liver injury, inflammation, and fibrosis compared with ethanol-induced liver disease models, and this positively correlated with the level of lipopolysaccharide translocation. CONCLUSIONS: More significant liver injury, inflammation, and fibrosis are seen in diet-induced steatohepatitis, which positively correlates with translocation of bacterial components, but not intact bacteria.
Asunto(s)
Hepatitis Alcohólica , Hepatopatías Alcohólicas , Enfermedad del Hígado Graso no Alcohólico , Ratones , Animales , Etanol/efectos adversos , Enfermedad del Hígado Graso no Alcohólico/patología , Traslocación Bacteriana , Lipopolisacáridos , Hígado/patología , Hepatopatías Alcohólicas/complicaciones , Hepatitis Alcohólica/complicaciones , Inflamación/patología , Dieta , Bacterias , Fibrosis , Ratones Endogámicos C57BL , Modelos Animales de EnfermedadRESUMEN
Anemia is a common complication of hepatitis B-related acute-on-chronic liver failure (HB-ACLF). Eryptosis, a suicidal erythrocyte death characterized by phosphatidylserine (PS) externalization and red blood cell-derived microparticle (RMP) generation, decreases erythrocyte lifespan. Herein, we investigated whether enhanced eryptosis is involved in the anemia pathophysiology associated with HB-ACLF. PS exposure, cell volume, cytosolic Ca2+, and reactive oxygen species (ROS) production were determined using flow cytometry. RMPs were extracted using a polyethylene glycol (PEG)-based method. We found that hemoglobin (Hb) and hematocrit (Hct) were significantly lower in patients with HB-ACLF than in healthy controls (HC), patients with chronic hepatitis B (CHB), and patients with cirrhosis. The direct antiglobulin test positive rate was 75.9% in patients with HB-ACLF while its intensity was associated with anemia. The ratio of abnormal erythrocytes was higher in patients with HB-ACLF than in HC, CHB, and cirrhosis. The percentage of PS-exposed erythrocytes was higher in patients with HB-ACLF (2.07 ± 0.11%) compared with HC (0.37 ± 0.05%), CHB (0.38 ± 0.03%), and cirrhosis (0.38 ± 0.04%). The cytosolic Ca2+ and ROS abundance were also higher in patients with HB-ACLF compared with HC, patients with CHB, and patients with cirrhosis, and were inversely correlated with the anemia in patients with HB-ACLF. PS exposure of erythrocytes collected from HC was significantly pronounced following incubation in plasma from patients with HB-ACLF compared with incubation in plasma from HC. The protein concentration and RMPs size significantly increased in patients with HB-ACLF compared with HC. Thus, the anemia in patients with HB-ACLF is associated with increased eryptosis, which is partially triggered by increased cytosolic Ca2+ and oxidative stress.NEW & NOTEWORTHY Acute chronic liver failure (ACLF) is a critical syndrome characterized by multiple organ failures and high short-term mortality. A common complication of HB-ACLF is anemia, however, the mechanism of anemia in HB-ACLF remains to be elucidated. We confirm that the accelerated eryptosis is involved in the pathophysiology of anemia associated with HB-ACLF, which progressively aggravates the clinical outcome. Our study illustrates the mechanism regarding the anemia pathogenesis of HB-ACLF, which may be utilized further toward therapeutic ends.
Asunto(s)
Insuficiencia Hepática Crónica Agudizada , Anemia , Eriptosis , Hepatitis B Crónica , Hepatitis B , Insuficiencia Hepática Crónica Agudizada/complicaciones , Anemia/complicaciones , Hepatitis B/complicaciones , Hepatitis B Crónica/complicaciones , Humanos , Cirrosis Hepática/complicaciones , Fosfatidilserinas/metabolismo , Especies Reactivas de Oxígeno/metabolismoRESUMEN
An attack of congestive heart failure (CHF) can cause symptoms such as difficulty breathing, dizziness, or fatigue, which can be life-threatening in severe cases. An electrocardiogram (ECG) is a simple and economical method for diagnosing CHF. Due to the inherent complexity of ECGs and the subtle differences in the ECG waveform, misdiagnosis happens often. At present, the research on automatic CHF detection methods based on machine learning has become a research hotspot. However, the existing research focuses on an intra-patient experimental scheme and lacks the performance evaluation of working under noise, which cannot meet the application requirements. To solve the above issues, we propose a novel method to identify CHF using the ECG-Convolution-Vision Transformer Network (ECVT-Net). The algorithm combines the characteristics of a Convolutional Neural Network (CNN) and a Vision Transformer, which can automatically extract high-dimensional abstract features of ECGs with simple pre-processing. In this study, the model reached an accuracy of 98.88% for the inter-patient scheme. Furthermore, we added different degrees of noise to the original ECGs to verify the model's noise robustness. The model's performance in the above experiments proved that it could effectively identify CHF ECGs and can work under certain noise.
Asunto(s)
Electrocardiografía , Insuficiencia Cardíaca , Algoritmos , Insuficiencia Cardíaca/diagnóstico , Humanos , Redes Neurales de la ComputaciónRESUMEN
Neuronal-regulated cell death (RCD) due to the accumulation of ROS within the central nervous system (CNS) is one of the crucial causes of central system diseases. Caspase-dependent apoptosis is the only form of RCD. As research progressed, several nonapoptotic cell death pathway RCDs were identified. Ferroptosis is a nonapoptotic RCD characterized by lipid peroxidation and plasma membrane damage. Polygonatum cyrtonema Hua. Polysaccharides (PCP) are an effective antioxidant. Based on this, the protective effect and mechanism of PCP against H2O2-induced microglial injury were investigated. Furthermore, the protective mechanism of PCP against ferroptosis in microglia was explored. Our results indicated that PCP could reduce oxidative stress-induced ROS accumulation by activating the NRF2/HO-1 signaling pathway, thus attenuating RCD in microglia. Subsequent studies have revealed that PCP alleviates ferroptosis in microglia due to protein levels of ERASTIN/RSL3 inhibitor SLC7A11/GPX4 by activating the NRF2/HO-1 signaling pathway. Therefore, we hypothesized that PCP exerts antioxidative and anti-ferroptosis effects by activating the expression of the NRF2/HO-1 pathway. This facilitates new ideas for clinically effective prevention and treatment of diseases due to accumulated reactive oxygen species in the CNS. Simultaneously, PCP has the development potential as a new drug candidate for treating CNS diseases.
Asunto(s)
Factor 2 Relacionado con NF-E2 , Polygonatum , Especies Reactivas de Oxígeno/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Antioxidantes/farmacología , Antioxidantes/metabolismo , Microglía/metabolismo , Peróxido de Hidrógeno/farmacología , Estrés Oxidativo , Polisacáridos/farmacologíaRESUMEN
In this study, a green and effective extraction method was proposed to extract two main compounds, ginsenosides and polysaccharides, from American ginseng by combining deep eutectic solvents (DESs) with aqueous two-phase systems. The factors of type of DESs, water content in DESs, the solid-liquid ratio, extraction temperature, and extraction time were studied in the solid-liquid extraction. Then, the aqueous two-phase system (DESs-ethylene oxide-propylene oxide (EOPO)) and salty solution exchange (EOPO-salty solution) was applied for the purification of polysaccharides. The content of the polysaccharides and ginsenosides were analyzed by the anthrone-sulfuric acid method and HPLC method, which showed that the extraction efficiency of deep eutectic solvents (DESs) was better than conventional methods. Moreover, the antioxidant activities of ginseng polysaccharides and their cytotoxicity were further assayed. The advantages of the current study are that, throughout the whole extraction process, we avoided the usage of an organic reagent. Furthermore, the separated green solvent DESs and EOPO could be recovered and reused for a next cycle. Thus, this study proposed a new, green and recyclable extraction method for extracting ginsenosides and polysaccharides from American ginseng.
Asunto(s)
Ginsenósidos , Panax , Disolventes Eutécticos Profundos , Polisacáridos , AguaRESUMEN
Coicis Semen is a common bulk medicinal material used for both medicine and food, which has the effect of promoting diuresis, draining dampness, invigorating the spleen and checking diarrhea. It is derived from Coix lacryma-jobi var. ma-yuen of the family Poaceae, and is easily contaminated by fungi such as Fusarium graminearum and F. flavum due to climate reasons to produce vomitoxin. The guiding principles for determination of vomitoxin in Chinese medicinal materials in Chinese Pharmacopoeia are mainly HPLC and LC-MS, which have long detection period and are time-consuming and laborious, and thus cannot meet the requirements of on-site quality inspection of drugs. The complete antigen of vomitoxin-protein was obtained by chemical derivatization of vomitoxin. The monoclonal antibody against vomitoxin was prepared by classic monoclonal antibody preparation technology, and enzyme-linked immunosorbent assay(ELISA) method for detection of vomitoxin in Coicis Semen was established through methodological investigation. The IC_(50) based on the ELISA for vomitoxin in Coicis Semen was 3.88 µg·L~(-1), and the average recoveries and the RSD were 77.32%-93.73% and 4.6%-9.7%, respectively. With the established ELISA method, the vomitoxin residue in 14 batches of Coicis Semen samples were determined and validated by LC-MS, and the correlation between the two assays was found to be 0.997 8, indicating that the established ELISA method could be used for quantitative determination of vomitoxin residue in Coicis Semen and could achieve the rapid quantitative determination of the vomitoxin residue.
Asunto(s)
Coix , Tricotecenos , Anticuerpos Monoclonales , Ensayo de Inmunoadsorción EnzimáticaRESUMEN
For further development and utilization of the germplasm resources of Puerariae Thomsonii Radix and Puerariae Lobatae Radix, this study developed the ultra performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) method, high performance liquid chromatography(HPLC) method, and anthrone colorimetry to detect the content of 23 flavonoids, cellulose, hemicellulose, lignin, soluble sugar, and starch in Puerariae Thomsonii Radix and Puerariae Lobatae Radix. The content differences of various chemical components were analyzed. The methodological test of the established UPLC-MS/MS method for the determination of flavonoids showed that each component had satisfactory linearity within the corresponding linear range(R~2≥0.995), and the average spiked recoveries were 94.48%-105.5%. With this method, 17 flavonoids in Puerariae Lobatae Radix and Puerariae Thomsonii Radix were detected. Based on HPLC and anthrone colorimetry, the determination methods of lignocellulose, soluble sugar, and starch were established. According to the determination results, the content of cellulose in Puerariae Thomsonii Radix was significantly lower than that in Puerariae Lobatae Radix, and the content of starch was significantly higher than that in Puerariae Lobatae Radix. The content of hemicellulose, lignin, and soluble sugar showed no significant difference between the two medicinals, and the content of soluble sugar was in highly significantly negative correlation with that of starch. The established methods are simple, rapid, accurate, and sensitive. The results can lay a basis for the evaluation, and comprehensive development and utilization of the germplasm resources of Puerariae Thomsonii Radix and Puerariae Lobatae Radix.
Asunto(s)
Medicamentos Herbarios Chinos , Pueraria , Antracenos , Cromatografía Líquida de Alta Presión , Cromatografía Liquida , Medicamentos Herbarios Chinos/química , Flavonoides/análisis , Lignina , Pueraria/química , Almidón , Azúcares , Espectrometría de Masas en TándemRESUMEN
Puerarin was conjugated with bovine serum albumin(BSA) and ovalbumin(OVA) by periodate oxidation to serve as the immunogen and coating antigen, respectively. BALB/c mice were immunized with puerarin-BSA according to the routine immunization procedure, and the titer and specificity of serum were detected after three immunization. After booster immunization, mouse spleen lymphocytes were fused with mouse myeloma cells, and 24 hybridoma cell lines of the monoclonal antibodies against puerarin were screened by monoclonal antibody screening technique. Ascites was prepared and purified. The cross-reactivity of monoclonal antibody(mAb) M1 with 4'-methoxy puerarin, daidzin, puerarin-6â³-O-xyloside, daidzein, mirificin, 3'-methoxy puerarin, and 3'-hydroxy puerarin was 239.84%, 112.18%, 67.89%, 58.28%, 22.37%, 0.40%, and 0.20%, respectively, and those with other analogs such as baicalein and baicalin were all less than 0.10%. The IC_(50) and the working range of the indirect competitive enzyme-linked immunosorbent assay(icELISA) for puerarin were 44.80 ng·mL~(-1) and 8.20-292.30 ng·mL~(-1), respectively. The average recovery was 91.95%-98.20% with an RSD in the range of 0.70%-2.60%. The content of puerarin in different Puerariae Lobatae Radix samples was determined with icELISA and validated by UPLC-MS. The correlation between data obtained from icELISA and UPLC-MS was 0.999 0, indicating that icELISA is suitable for the rapid detection of puerarin in Puerariae Lobatae Radix samples.
Asunto(s)
Anticuerpos Monoclonales , Espectrometría de Masas en Tándem , Animales , Cromatografía Liquida , Ensayo de Inmunoadsorción Enzimática/métodos , Hibridomas/metabolismo , Isoflavonas , Ratones , Ratones Endogámicos BALB CRESUMEN
BACKGROUND: Multiple factors contribute to anemia in patients with Hepatitis B virus (HBV)related acute-on-chronic liver failure (ACLF); however, the mechanism is unclear. The purpose of this study was to evaluate the clinical significance of the direct antiglobulin test (DAT) in patients with HBV related ACLF. METHODS: DAT was used to detect immunoglobulins and/or complement proteins on the surface of erythrocytes. RESULTS: We recruited 78 HBV-associated ACLF patients, 30 chronic hepatitis B(CHB)patients and 40 healthy people between October 2015 and May 2016. In HBV related ACLF patients, the hemoglobin concentration, number of erythrocytes, and hematocrit value were significantly lower, while the erythrocyte distribution width was significantly higher, compared to patients with CHB and healthy controls (HCs) (P < 0.001). The rates of DAT positivity in HBV related ACLF patients, CHB patients, and HCs were 62.8 %, 13.3 %, and 0%, respectively. DAT-positive ACLF patients exhibited lower Hb levels, older average age, as well as higher total bilirubin, alanine aminotransferase, and complement component 3 levels compared to DAT-negative patients. CONCLUSIONS: HBV related ACLF patients showed significant alterations in erythrocyte parameters, possibly reflecting disease development and severity. The high presence of erythrocyte autoantibodies suggested that immunologic clearance of erythrocytes contributed to multifactorial anemia in HBV related ACLF patients.
Asunto(s)
Insuficiencia Hepática Crónica Agudizada/sangre , Prueba de Coombs/métodos , Hemoglobinas/análisis , Hepatitis B Crónica/sangre , Insuficiencia Hepática Crónica Agudizada/complicaciones , Adulto , Anciano , Alanina Transaminasa/sangre , Bilirrubina/sangre , Proteínas del Sistema Complemento , Eritrocitos/citología , Femenino , Hepatitis B Crónica/complicaciones , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los ResultadosRESUMEN
A definitive diagnosis of heparin-induced thrombocytopenia (HIT) is difficult to make, especially in patients undergoing cardiac surgery. In this retrospective cohort study, we assessed the platelet count trends and the response to fondaparinux in a population of patients of suspected HIT after pulmonary endarterectomy (PEA). Patients enrolled in this study were over the age of 18 years, and survived longer than 7 days after PEA between January 1, 2011 and December 31, 2015. HIT likelihood was assessed by the 4 T's score and interpreted by our institutional algorithm. 54 patients were operated, and 49 patients met the inclusion criteria. Six patients met the criteria for suspected HIT and were treated with fondaparinux until the platelet recovered. No significant difference was observed of clinical characteristics between intermediate to high HIT likelihood patients (HIT SUSPECTED) and low HIT likelihood patients (NO HIT SUSPECTED). HIT SUSPECTED patients reached platelet count lowest later (about 5.5 days after PEA), while NO HIT SUSPECTED patients is about 4.0 days after PEA. Percentage of platelet counts decrease (> 50%) was larger than NO HIT SUSPECTED patients (< 50%). There was no difference in mortality or residual pulmonary hypertension between HIT SUSPECTED and NO HIT SUSPECTED patients. Two HIT SUSPECTED patients who used heparin after PEA died, the other four survived by replacing heparin or low molecular weight heparin with fondaparinux. Suspected HIT patients should be surveilled carefully. Platelet counts trends may have some hints in the prevention of HIT. Fondaparinux may be effective for patients with suspected HIT.
Asunto(s)
Endarterectomía/efectos adversos , Fondaparinux/administración & dosificación , Heparina/efectos adversos , Hipertensión Pulmonar , Recuento de Plaquetas , Complicaciones Posoperatorias , Trombocitopenia , Adulto , China/epidemiología , Estudios de Cohortes , Endarterectomía/métodos , Inhibidores del Factor Xa/administración & dosificación , Femenino , Heparina/administración & dosificación , Humanos , Hipertensión Pulmonar/diagnóstico , Hipertensión Pulmonar/etiología , Hipertensión Pulmonar/prevención & control , Masculino , Persona de Mediana Edad , Recuento de Plaquetas/métodos , Recuento de Plaquetas/estadística & datos numéricos , Complicaciones Posoperatorias/sangre , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/prevención & control , Embolia Pulmonar/complicaciones , Embolia Pulmonar/mortalidad , Embolia Pulmonar/cirugía , Ajuste de Riesgo/métodos , Trombocitopenia/sangre , Trombocitopenia/inducido químicamente , Trombocitopenia/diagnóstico , Trombocitopenia/epidemiologíaRESUMEN
Traditional Chinese medicine (TCM) is not only an effective solution for primary health care, but also a great resource for drug innovation and discovery. To meet the increasing needs for TCM-related data resources, we developed ETCM, an Encyclopedia of Traditional Chinese Medicine. ETCM includes comprehensive and standardized information for the commonly used herbs and formulas of TCM, as well as their ingredients. The herb basic property and quality control standard, formula composition, ingredient drug-likeness, as well as many other information provided by ETCM can serve as a convenient resource for users to obtain thorough information about a herb or a formula. To facilitate functional and mechanistic studies of TCM, ETCM provides predicted target genes of TCM ingredients, herbs, and formulas, according to the chemical fingerprint similarity between TCM ingredients and known drugs. A systematic analysis function is also developed in ETCM, which allows users to explore the relationships or build networks among TCM herbs, formulas,ingredients, gene targets, and related pathways or diseases. ETCM is freely accessible at http://www.nrc.ac.cn:9090/ETCM/. We expect ETCM to develop into a major data warehouse for TCM and to promote TCM related researches and drug development in the future.
Asunto(s)
Bases de Datos Farmacéuticas , Medicamentos Herbarios Chinos , Medicina Tradicional China , Enfermedad/genética , Descubrimiento de Drogas , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/normas , Humanos , Interfaz Usuario-ComputadorRESUMEN
BACKGROUND: Fucosyltransferase 2 (Fut2)-mediated intestinal α1-2-fucosylation is important in maintaining a symbiotic host-microbiota relationship and can protect against several pathogens. Intestinal dysbiosis is an important factor for the progression of experimental ethanol (EtOH)-induced liver disease, but the role of Fut2 in modulating the intestinal glycocalyx during alcohol-associated liver disease is unknown. We investigated the role of Fut2-mediated intestinal α1-2-fucosylation for the development of alcohol-associated liver disease. METHODS: Immunohistochemistry staining was applied to evaluate α1-2-fucosylation in duodenal biopsies from patients with alcohol use disorder. Wild-type (WT) and Fut2-deficient littermate mice were subjected to Lieber-DeCarli models of chronic EtOH administration and the chronic-binge EtOH diet (NIAAA model). RESULTS: Intestinal α1-2-fucosylation was down-regulated in patients with alcohol use disorder. Lack of α1-2-fucosylation in Fut2-deficient mice exacerbates chronic EtOH-induced liver injury, steatosis, and inflammation without affecting EtOH metabolism. Dietary supplementation of the α1-2-fucosylated glycan 2'-fucosyllactose (2'-FL) ameliorates EtOH-induced liver disease in Fut2-deficient mice in the NIAAA model. Despite no direct effects on growth of Enterococcus faecalis in vitro, intestinal α1-2-fucosylation reduces colonization of cytolysin-positive E. faecalis in the intestine of EtOH-fed mice. CONCLUSIONS: Intestinal α1-2-fucosylation acts as a host-protective mechanism against EtOH-induced liver disease. 2'-FL is an oligosaccharide naturally present in human milk that could be considered as therapeutic agent for alcohol-associated liver disease.
Asunto(s)
Alcoholismo/metabolismo , Disbiosis/genética , Fucosiltransferasas/genética , Hepatopatías Alcohólicas/genética , Hígado/efectos de los fármacos , Alcoholismo/genética , Alcoholismo/microbiología , Animales , Depresores del Sistema Nervioso Central/toxicidad , Modelos Animales de Enfermedad , Disbiosis/metabolismo , Disbiosis/microbiología , Etanol/toxicidad , Fucosiltransferasas/metabolismo , Microbioma Gastrointestinal/efectos de los fármacos , Glicocálix/efectos de los fármacos , Glicocálix/metabolismo , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/metabolismo , Hígado/metabolismo , Hígado/patología , Hepatopatías Alcohólicas/metabolismo , Hepatopatías Alcohólicas/microbiología , Ratones , Galactósido 2-alfa-L-FucosiltransferasaRESUMEN
Ophiocordyceps xuefengensis (O. xuefengensis), a new species of caterpillar fungus, has been identified as the sister taxon of Ophiocordyceps sinensis (O. sinensis). The aims of the present study are to evaluate the anticancer activity and to qualitatively analyze the potential bioactive chemical constituents of O. xuefengensis and O. sinensis, comparatively. An MTT assay was used to evaluate the in vitro anticancer activities of different fractions from O. xuefengensis and O. sinensis. The results show that ethyl acetate fractions of O. xuefengensis and O. sinensis have significant in vitro anticancer activity. These two bioactive fractions were analyzed by ultra-performance liquid chromatography-electrospray ionization with quadrupole-time of flight tandem mass spectrometry technology. A total of 82 compounds and 101 compounds were identified or tentatively characterized in the bioactive fractions of O. xuefengensis and O. sinensis, respectively. Among these compounds, 68 existed in both O. xuefengensis and O. sinensis. A total of 67 compounds were reported in O. xuefengensis and 8 compounds were reported in caterpillar fungus for the first time. This is the first detailed comparative analysis of the in vitro anticancer activity and chemical ingredients between O. xuefengensis and O. sinensis. The application of this work will provide reliable fundamental pharmacological substances for the use of O. xuefengensis by Yao people.