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1.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(5): 1540-1547, 2021 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-34627437

RESUMO

OBJECTIVE: To analyze the disease types, clinical manifestations, efficacy and outcome of JAK2 V617F and BCR-ABL double-mutant myeloproliferative neoplasms (MPN), and provide a reference for the diagnosis, treatment and prognosis of MPN. METHODS: The clinical characteristics, diagnosis, therapeutic efficacy and outcome of JAK2 V617F and BCR-ABL double-mutant MPN were analyzed comprehensitively by combining a clinical case diagnosed and treated in our hospital with literature cases from CNKI and PubMed databases. RESULTS: A total of 38 related literatures were retrieved from the two databases by searching "JAK2 V617F" and "BCR-ABL" as key words from 1990 to 2019, and 59 cases were involved. Among all the 60 cases, 41 were males (68.3%) with a median age of 61 (32-77) years old, while 19 were females (31.7%) with a median age of 58 (21-82) years old. The BCR-ABL fusion gene and JAK2 V617F mutation were found simultaneously in 21 cases (35%), 19 cases (31.7%) with JAK2 V617F mutation were found during the treatment of Philadelphia chromosome (Ph)-positive chronic myelogenous leukemia (CML). Ph+CML was detectable in 20 cases (33.3%) during the treatment of JAK2 V617F mutation positive MPN. Polycythemia vera (PV) was the most common MPN coexisting with CML (30%), followed by essential thrombocythemia (ET) (26.7%) and primary myelofibrosis (PMF) (21.7%). In addition, there were 13 cases (21.7%) not classified in the literature. Among the 60 cases, 35 CML patients were clearly staged, including 31 in the chronic phase, 3 in the accelerated phase, and 1 in the blast crisis phase. As for the subtypes of BCR-ABL fusion gene, there were 30 cases with clear classification, including 28 cases of p210, 1 case of p190 and 1 case of p230. CONCLUSION: As cases of BCR-ABL and JAK2 V617F double-mutant MPN are reported, simultaneous detection of JAK2 V617F mutation and BCR-ABL fusion gene in MPN patients is necessary to avoid misdiagnosis and missed diagnosis.


Assuntos
Transtornos Mieloproliferativos , Policitemia Vera , Trombocitemia Essencial , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Proteínas de Fusão bcr-abl/genética , Humanos , Janus Quinase 2/genética , Masculino , Pessoa de Meia-Idade , Transtornos Mieloproliferativos/genética , Adulto Jovem
2.
Front Pharmacol ; 12: 747450, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34658883

RESUMO

Remdesivir, a nucleotide analog prodrug, has displayed pharmacological activity against SARS-CoV-2. Recently, eicosanoids are widely involved in regulating immunity and inflammation for COVID-19 patients. Rats were intravenously administered remdesivir at a dose of 5 mg/kg, and series of blood samples were collected before and after treatment. Targeted metabolomics regarding the eicosanoid profile were investigated and quantitated simultaneously using the previously reported reliable HPLC-MS/MS method. Additionally, interplay relationship between metabolomics and pharmacokinetic parameters was performed using the Pearson correlation analysis and PLS model. For the longitudinal metabolomics of remdesivir, metabolic profiles of the same rat were comparatively substantial at discrete sampling points. The metabolic fingerprints generated by individual discrepancy of rats were larger than metabolic disturbance caused by remdesivir. As for the transversal metabolomics, the prominent metabolic profile variation was observed between the baseline and treatment status. Except for TXB2, the inflammatory- and immunology-related eicosanoids of resolvin D2, 5-HEPE, 5-HETE, and DHA were significantly disturbed and reduced after single administration of remdesivir (p < 0.05, p < 0.001). Moreover, the metabolite of PGE2 correlated with GS-441524 (active metabolite of remdesivir) concentration and pharmacokinetic parameters of Cmax, AUC0-t, AUC0-infinity, and CL significantly. Eicosanoid metabolic profiles of remdesivir at both longitudinal and transversal levels were first revealed using the robust HPLC-MS/MS method. This initial observational eicosanoid metabolomics may lighten the therapy for fighting COVID-19 and further provide mechanistic insights of SARS-CoV-2 virus infection.

3.
J Tradit Chin Med ; 41(4): 588-599, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34392652

RESUMO

OBJECTIVE: To identify active compounds in an Yinyanghuo (Herba Epimedii Brevicornus) - Xianmao (Rhizoma Curculiginis) drug pair (ECD) and investigate its efficacy on polycystic ovary syndrome (PCOS), and its possible mechanism in a rat model of PCOS. METHODS: A network pharmacology approach involving a characteristic drug assessment, active compound and target prediction, PCOS gene collection as well as network analysis was employed. The ovary morphology after treatment was observed using an animal model and western blotting and real-time PCR were used to verify AKT1 as the molecular target. RESULTS: Six networks were constructed, an active compound-target network for the ECD (C-T network), a drug-target network (D-T network), a related genes network, a targets interaction network, a key genes interaction network, and a gene-pathway network. A total of 41 compounds and 261 targets were identified for the ECD, 232 PCOS-related genes, 31 cogenes, and 14 pathways. These pathways may be involved in the efficacy of ECD on PCOS. The proteins most involved in the signal pathways for all targets were AKT1, IL6, INSR, ESR, and GSK3B. The AKT1 target was selected for experimental verification. Based on the Western blot and real-time PCR results, the expression of AKT1 in the PCOS model varied after treatment with ECD. CONCLUSIONS: Our findings suggest that the ECD can reverse the negative morphological changes in ovarian tissue that occur in model rats of PCOS. AKT1 may be a key mediator of the observed ability of the ECD to protect against PCOS in the model rats.

4.
Mikrochim Acta ; 188(7): 234, 2021 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-34160693

RESUMO

Coral-like Ag-Mo2C/C-I and blocky Ag-Mo2C/C-II composites were obtained from one-step in situ calcination of [Ag(HL)3(Mo8O26)]n·nH2O [L: N-(pyridin-3-ylmethyl) pyridine-2-amine] under N2/H2 and N2 atmospheres, respectively. The coral-like morphology of Ag-Mo2C/C-I is composed of interwoven nanorods embedded with small particles, and the nano-aggregate of Ag-Mo2C/C-II is formed by cross-linkage of irregular nanoparticles. The above composites are decorated on glassy carbon electrode (GCE) drop by drop to generate two enzyme-free electrochemical sensors (Ag-Mo2C/C/GCE) for amperometric detection of H2O2. In particular, the coral-like Ag-Mo2C/C-I/GCE sensor possesses rapid response (1.2 s), high sensitivity (466.2 µA·mM-1·cm-2), and low detection limit (25 nM) towards trace H2O2 and has wide linear range (0.08 µM~4.67 mM) and good stability. All these sensing performances are superior to Ag-Mo2C/C-II/GCE, indicating that the calcining atmosphere has an important influence on microstructure and electrochemical properties. The excellent electrochemical H2O2 sensing performance of Ag-Mo2C/C-I/GCE sensor is mainly attributed to the synergism of unique microstructure, platinum-like electron structure of Mo2C, strong interaction between Mo and Ag, as well as the increased active sites and conductivity caused by co-doped Ag and carbon. Furthermore, this sensor has been successfully applied to the detection of H2O2 in human serum sample, contact lens solution, and commercial disinfector, demonstrating the potential in related fields of environment and biology. Graphical abstract.

5.
Leuk Lymphoma ; 62(11): 2657-2664, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34105439

RESUMO

In this study, we aimed to investigate treatment options and the prognosis of patients with WM in China. This retrospective study included 1141 patients diagnosed with symptomatic WM between January 2003 and December 2019 at 35 tertiary hospitals in 22 provinces of China. Fifty-four patients (7.3%) received monotherapy, 264 (36.0%) received chemoimmunotherapy, 395 (53.8%) received other combination regimens without rituximab, and 21 (2.9%) received ibrutinib. Using a multivariable Cox regression model, age > 65 years old, platelets <100 × 109/L, serum albumin <3.5 g/dl, ß2 microglobulin concentration ≥4 mg/L and LDH ≥250 IU/L predicted poor OS. In summary, our study showed that frontline treatment choices for WM are widely heterogeneous. We validated most of the established prognostic factors in the rIPSS (age >65 years, LDH ≥250 IU/L, ALB <3.5 g/dl and ß2 microglobulin ≥4 mg/L) together with PLT ≤ 100 × 109/L indicate a poor prognosis for patients with WM.


Assuntos
Macroglobulinemia de Waldenstrom , Idoso , Humanos , Prognóstico , Estudos Retrospectivos , Rituximab , Resultado do Tratamento , Macroglobulinemia de Waldenstrom/diagnóstico , Macroglobulinemia de Waldenstrom/tratamento farmacológico , Macroglobulinemia de Waldenstrom/epidemiologia
6.
Risk Manag Healthc Policy ; 14: 1233-1239, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33790668

RESUMO

Objective: Patients presenting with acute myocardial infarction (AMI) with prior digestive system disease are more likely to suffer from gastrointestinal (GI) bleeding than those without these diseases. However, few articles reported how the different conditions of the digestive tract produced different risks of GI bleeding. Methods: A single-center study on 7464 patients admitted for AMI from December 2010 to June 2019 in the Beijing Chaoyang Heart Center was retrospectively examined. Patients with major GI bleeding (n = 165) were compared with patients without (n = 7299). Univariate and multivariate logistic regression models were constructed to test the association between GI bleeding and prior diseases of the digestive tract, including gastroesophageal reflux disease, chronic gastritis, peptic ulcer, hepatic function damage, diseases of the colon and rectum, and gastroenterological tract tumors. Results: Of the 7464 patients (mean age, 63.4; women, 25.6%; STEMI, 58.6%), 165 (2.2%) experienced major GI bleeding, and 1816 (24.3%) had a history of digestive system disease. The risk of GI bleeding was significantly associated with peptic ulcer (OR = 4.19, 95% CI: 1.86-9.45) and gastroenterological tumor (OR = 2.74, 95% CI: 1.07-7.04), indicated by multivariate logistic regression analysis. Conclusion: Preexisting peptic ulcers and gastroenterological tract tumors rather than other digestive system diseases were indicators of gastrointestinal bleeding in patients with AMI who undergo standard antithrombotic treatment during hospitalization.

7.
Biomed Pharmacother ; 138: 111441, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33652261

RESUMO

Metabolic syndrome (MetS) is a complex, multifactorial disease which lead to an increased risk of cardiovascular disease, type 2 diabetes, and stroke. However, selective, and potent drugs for the treatment of MetS are still lacking. Previous studies have found that Akebia saponin D (ASD) has beneficial effects on metabolic diseases such as obesity, atherosclerosis, and non-alcoholic fatty liver disease (NAFLD). Therefore, our study was designed to determine the effect and mechanism of action of ASD against MetS in a high-fat diet (HFD) induced mouse model. ASD significantly decreased plasma lipid and insulin resistance in these mice, and a targeted approach using metabolomic analyses of plasma and feces indicated that glucose and lipids in these mice crossed the damaged intestinal barrier into circulation. Furthermore, ASD was able to increase lipid excretion and inhibit intestinal epithelial lipid absorption. Results for gut microbiota composition showed that ASD significantly reduced HFD-associated Alistipes, Prevotella, and enhanced the proportions of Butyricimonas, Ruminococcus, and Bifidobacterium. After 14 weeks of ASD/fecal microbiota transplantation (FMT) interventions the developed gut barrier dysfunction was restored. Additionally, RNA-seq revealed that ASD reduced the lipid-induced tight junction (TJ) damage in intestinal epithelial cells via down-regulation of the PPAR-γ-FABP4 pathway in vitro and that use of the PPAR-γ inhibitor (T0070907) was able to partially block the effects of ASD, indicating that the PPAR-γ/FABP4 pathway is a critical mediator involved in the improvement of MetS. Our results demonstrated that ASD not only modifies the gut microbiome but also ameliorates the HFD-induced gut barrier disruption via down-regulation of the PPAR-γ-FABP4 pathway. These findings suggest a promising, and novel therapeutic strategy for gut protection against MetS.


Assuntos
Microbioma Gastrointestinal/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Síndrome Metabólica/tratamento farmacológico , Saponinas/uso terapêutico , Animais , Linhagem Celular , Transplante de Microbiota Fecal/métodos , Microbioma Gastrointestinal/fisiologia , Humanos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Masculino , Síndrome Metabólica/metabolismo , Síndrome Metabólica/patologia , Camundongos , Camundongos Endogâmicos C57BL , Saponinas/farmacologia
8.
J Reconstr Microsurg ; 37(7): 580-588, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33592636

RESUMO

BACKGROUND: This study is to describe the distribution of natural true anastomoses associated with the distally based perforator-plus sural neurocutaneous flap (sural flap), summarize our experience in the flap with high pivot point, and compare the outcomes between the flaps with high and low pivot points. METHODS: Five amputated lower limbs were perfused, and the integuments were radiographed. We retrospectively analyzed 378 flaps, which were divided into two groups: pivot points located ≤8.0 cm (low pivot point group) and >8.0 cm (high pivot point group) proximal to the tip of the lateral malleolus. Partial necrosis rates were compared between two groups. RESULTS: The arterial chain surrounding the sural nerve was linked by true anastomoses from the intermalleolar line to popliteal crease. True anastomoses existed among peroneal perforators and between these perforators and the arterial chain. There were 93 flaps with high pivot point and 285 flaps with low pivot point. Partial necrosis rates were 16 and 9.1% in the high and low pivot point group (p = 0.059), respectively. CONCLUSION: True anastomosis connections among peroneal perforators and the whole arterial chain around sural nerve enable the sural flap to survive with a greater length. The sural flap with high pivot point is a good option for reconstructing soft-tissue defects in the middle and distal leg, ankle, and foot, particularly when the lowest peroneal perforator presents damage, greater distance to the defects, discontinuity with the donor site, or anatomical variation.


Assuntos
Retalho Perfurante , Procedimentos Cirúrgicos Reconstrutivos , Lesões dos Tecidos Moles , Tornozelo , , Humanos , Estudos Retrospectivos , Lesões dos Tecidos Moles/cirurgia , Nervo Sural
9.
Anal Chim Acta ; 1143: 73-83, 2021 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-33384132

RESUMO

Fabrication of non-enzymatic electrochemical sensors based on metal oxides with low valence-state for nanomolar detection of H2O2 has been a great challenge. In this work, a novel neuron-network-like Cu-MoO2/C hierarchical structure was simply prepared by in-situ pyrolysis of 3D bimetallic-organic framework [Cu(Mo2O7)L]n [L: N-(pyridin-3-ylmethyl)pyridine-2-amine] crystals. Meanwhile, the MoO2/C nano-aggregates were also obtained by liquid phase copper etching. Subsequently, two non-enzymatic electrochemical sensors were fabricated by simple drop-coating of the above two materials on the surface of glassy carbon electrode (GCE). Electrochemical measurements indicate that the Cu-MoO2/C/GCE possesses highly efficient electrocatalytic H2O2 property during wider linear range of 0.24 µM-3.27 mM. At room temperature, the Cu-MoO2/C composite displays higher sensitivity (233.4 µA mM-1 cm-2) and lower limit of detection (LOD = 85 nM), which are 1 and 2.5 times larger than those of MoO2/C material, respectively. Such excellent ability for trace H2O2 detection mainly originates from the synergism of neuron-network-like structure, enhanced electrical conductivity and increased active sites caused by low valence-state MoO2 and co-doping of Cu and carbon, and even the interaction between Cu and Mo. In addition, the H2O2 detection in spiked human serum and commercially real samples indicates that the Cu-MoO2/C/GCE sensor has certain potential application in the fields of environment and biology.


Assuntos
Técnicas Biossensoriais , Peróxido de Hidrogênio , Técnicas Eletroquímicas , Eletrodos , Humanos , Neurônios
10.
Cancer Chemother Pharmacol ; 87(1): 103-112, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33141329

RESUMO

OBJECTIVE: Rate-limiting enzyme 3b-hydroxysteroid dehydrogenase type 1 (3ßHSD1) encoded by HSD3B1 catalyzes the transition of dehydroepiandrosterone (DHEA) to dihydrotestosterone (DHT). The HSD3B1 (1245C) variant renders 3bHSD1 of resistant to ubiquitination and degradation, leading to a large amount of protein accumulation in the cell. Multiple clinical studies have shown that this mutation was correlated with resistance to androgen-deprivation therapy in prostate cancer. However, the results were not consistent depending on different treatment strategy and in some researches, the number of observed cases was relatively small. METHODS: To determine the effects of HSD3B1 (1245C) variant on resistance to androgen-deprivation therapy in prostate cancer, we performed a meta-analysis of the available literature. Electronic database searches identified appropriately designed studies that detected HSD3B1 in prostate cancer. We conducted a systematic search of studies in the following databases: PubMed, and EMBASE published until August 10, 2020 using the following search terms: (HSD3B1 AND ((((prostate cancer) OR prostatic neoplasm) OR prostatic carcinoma) OR prostatic cancer). RESULTS: Eight researches were included in this research. The result validated that the HSD3B1 (1245C) variant allele was associated with a shorter PFS (HR, 1.97; 95% CI, 1.39-2.79; P = 0.0001) (homozygous wild-type group) in men with prostate cancer when treated with ADT, however, a higher PFS (HR, 0.68; 95% CI, 0.48-0.96; P = 0.03) when treated with ADT and CYP17A1 inhibitor. CONCLUSION: The HSD3B1 (1245C) variant is a predictor of ADT plus CYP17A1 inhibitor response in prostate cancer.


Assuntos
Antagonistas de Androgênios/administração & dosagem , Complexos Multienzimáticos/genética , Progesterona Redutase/genética , Neoplasias da Próstata/tratamento farmacológico , Esteroide Isomerases/genética , Alelos , Antagonistas de Androgênios/farmacologia , Resistencia a Medicamentos Antineoplásicos , Humanos , Masculino , Mutação , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Esteroide 17-alfa-Hidroxilase/antagonistas & inibidores , Resultado do Tratamento
11.
J Nanosci Nanotechnol ; 21(1): 310-325, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33213632

RESUMO

Scanning electron microscopy (SEM) was used to analyze and study micron-nanometer evaporite samples collected from Paleocene and Eocene drill cores in the Jiangling Depression. Accordingly, seven beds of potassium-bearing solid rocks were accurately identified. Sylvite, carnallite, syngenite, dolomite, thenardite, anhydrite, glauberite, halite, barite, celestite, and other solid salt minerals were found, and carnallite, syngenite, and thenardite were found for the first time in the Jiangling Depression. Sylvite, syngenite, and carnallite indicate that the Paleogene salt lakes in the Jiangling Depression had evolved to the sylvite stage and that prospecting for solid sylvite would be satisfactory. Micron-nanometer celestite is contained in the evaporites, from which we can infer that strontium may have been provided by deep formation water (or oil-field water). This finding is of great significance to studying the genesis of sylvite sediment in the Jiangling Depression. From the extensive development of primary glauberite beds typical of warm salt minerals in the Shashi Formation, it can be inferred that the late Paleogene paleoclimate in the Jiangling Depression of the Jianghan Basin was dry and hot. Based on the extensive distribution of micron-nanometer pyrite, siderite, iron and Fe2O3/FeO ratios in evaporite sediments and color analysis of mudstones, the evaporites in the study area formed in an underwater anoxic, reducing environment during sedimentation. Therefore, the evaporite sediments in the Paleocene-Eocene interval of the Jiangling Depression are proposed to have formed in a saltwater lake sedimentary environment, and the ancient lake was characterized by a deep-water salt lake sedimentary model.

12.
Chin J Acad Radiol ; : 1-6, 2020 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-33225216

RESUMO

The COVID-19 epidemic has swept across China and spread to other countries. The rapid spreading of COVID-19 and panic combined with the lack of a hierarchical medical system in China have resulted in a huge number of hospital visiting which are overwhelming local medical system and increasing the incidence of cross infection. To meliorate this situation, we adopted the management concept of the system of Tiered Diagnosis and Treatment and developed an online tool for self-triage based on the mostly used multi-purpose smartphone app Wechat in China. This online tool helps people perform self-triage so that they can decide whether to quarantine at home or visit hospital. This tool further provides instructions for home quarantine and help patients make an appointment online if hospital visiting suggested. This smartphone application can reduce the burden on hospitals without losing the truly COVID-19 patients and protect people from the danger of cross infection.

13.
Oncol Lett ; 20(4): 21, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32774494

RESUMO

Clinical trials of chimeric antigen receptors (CARs) targeting CD19 have produced impressive results in hematological malignancies, including diffuse large B-cell lymphoma (DLBCL). However, a notable number of patients with DLBCL fail to achieve remission after CD19 CAR T-cell therapy and may therefore require a dual targeted CAR T-cell therapy. A 31-year-old man with refractory DLBCL was assessed in the present case report. The patient was treated with sequential infusion of single CD19 CAR T cells followed by dual CD19/CD22-targeted CAR T cells. The outcome was that the patient achieved partial remission after the first single CD19 CAR T-cell infusion and complete remission after the dual CD19/CD22-targeted CAR T-cell infusion. Grade 1 cytokine release syndrome (CRS) was observed after the single CD19 CAR T-cell infusion, while grade 3 CRS and hemophagocytic syndrome were observed after the dual targeted CAR T-cell infusion, but these adverse effects alleviated after the treatments. To the best of our knowledge, the present case report is the first to describe the successful application of dual CD19/CD22-targeted CAR T-cell therapy for the treatment of refractory DLBCL. The report suggests that dual CD19/CD22-targeted CAR T-cell therapy may represent a promising option for the treatment of refractory DLBCL; however, caution should be taken due to potential CRS development.

14.
Intervirology ; 63(1-6): 10-16, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32772018

RESUMO

BACKGROUND: This study was planned to investigate the association betweenhuman cytomegalovirus (HCMV) infection and gastrointestinal cancer (GIC) risk, by undertaking a meta-analysis and case-control cross-sectional study. SUMMARY: A cross-sectional study analysis of 160 GIC patients and 100 control subjects indicated significantly higher HCMV prevalence in GIC patients based on the HCMV IgM test. However, a similar analysis based on an IgG test revealed no significant relationship. Further meta-analysis of 11 studies, including 1,044 patients and 991 healthy subjects, displayed HCMV infection as an important risk factor for not only colorectal cancer occurrence and development based on a HCMV DNA test, but also for GIC based on a HCMV IgM test. However, the IgG test again displayed no significant relationship between HCMV infection and GIC occurrence. Key Message: Overall, our study revealed that HCMV infection is associated with an increased GIC risk. However, additional studies are warranted to elucidate the molecular mechanism underlying this association.


Assuntos
Infecções por Citomegalovirus/complicações , Neoplasias Gastrointestinais/etiologia , Idoso , Anticorpos Antivirais/sangue , Estudos Transversais , Citomegalovirus/genética , Citomegalovirus/imunologia , Citomegalovirus/isolamento & purificação , Infecções por Citomegalovirus/epidemiologia , DNA Viral/análise , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco
15.
Dis Markers ; 2020: 8842320, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32733621

RESUMO

Metabolic syndrome (MetS) is a health disorder characterized by metabolic abnormalities that predict an increased risk to develop cardiovascular disease (CVD) and type 2 diabetes. Biomarkers can provide an insight into the novel mechanism for MetS and can be potentially used for personalized response to therapies. We exploited a targeted HPLC-MS/MS method to characterize plasma amino acids and carnitine metabolic profile in MetS patients. A training set (40 cases and 40 controls) and validation set (80 MetS patients and 80 healthy controls) were carried out to find the metabolic profiles. We discovered two carnitine metabolites including hydroxydecanoyl carnitine and methylglutarylcarnitine. Our results indicated that the decreased level of hydroxydecanoyl carnitine and methylglutarylcarnitine may be associated with the risk of MetS. These biomarkers may improve the risk prediction and provide a novel tool for monitoring of the progression of disease and response to treatment in MetS patients.


Assuntos
Aminoácidos/sangue , Carnitina/sangue , Síndrome Metabólica/sangue , Metabolômica/métodos , Biomarcadores/sangue , Estudos de Casos e Controles , Cromatografia Líquida de Alta Pressão , Feminino , Humanos , Masculino , Espectrometria de Massas em Tandem
16.
Life Sci ; 257: 117658, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32621921

RESUMO

BACKGROUND: Curcumin (Cur) is a hydrophobic polyphenol compound derived from the rhizome of the herb Curcuma longa. Cur has a wide spectrum of biological and pharmacological activities. It has been shown that human cytomegalovirus (HCMV) infection was an important risk factor for atherosclerosis (AS) and Cur exhibited an outstanding anti-HCMV effect. However, anti-AS effects of Cur remain unclear when HCMV infected endothelial cells. AIMS: This study will investigate the anti-AS activities and mechanism of Cur,when HCMV infected in vivo and in vitro. MATERIALS AND METHODS: Cur (0.5, 1, and 2 µM) was used to explore the anti-AS activities and mechanism after HCMV infected endothelial cells in vitro. ApoE-/- mice were fed a high fat and cholesterol diet (HD) and given 4000,000 copies/mouse MCMV infection by intraperitoneal and treated with ganciclovir (5 mg/kg/d), Cur (25, 15 mg/kg/d) for 10 weeks in vivo. KEY FINDINGS: As our results showed that Cur inhibited CMV replication and proliferation, reduced the intracellular ROS overproduction, decreased the release of inflammatory cytokines, down-regulated the level of HMGB1-TLRS-NF-κB signaling pathway-related proteins in vitro experiments. Cur reduced the serum levels of LDL-C, TC and TG, significantly decreased the formation of atherosclerotic plaque in the aorta, reduced the lipid deposition in liver and inflammatory damage in heart, lung and kidney in vivo experiments. SIGNIFICANCE: This study showed that Cur prevent AS progression by inhibiting CMV activity and CMV-induced HMGB1-TLRS-NF-κB signaling pathway.


Assuntos
Aterosclerose/tratamento farmacológico , Curcumina/farmacologia , Citomegalovirus/efeitos dos fármacos , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Apolipoproteínas E/genética , Apolipoproteínas E/metabolismo , Aterosclerose/metabolismo , Curcuma/metabolismo , Curcumina/metabolismo , Citocinas/metabolismo , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Células Endoteliais da Veia Umbilical Humana , Humanos , Masculino , Camundongos , Camundongos Transgênicos , NF-kappa B/metabolismo , Extratos Vegetais/farmacologia , Placa Aterosclerótica/metabolismo , Transdução de Sinais/efeitos dos fármacos
17.
Scand J Immunol ; 92(2): e12912, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32458431

RESUMO

Immune processes in liver transplantation remain poorly understood. Acute allograft rejection in liver transplantation is a kind of T cell-mediated inflammatory disease accompanied by inflammatory cell infiltration. However, the effect of acute allograft rejection on the immunological characteristics of TCRs in peripheral blood mononuclear cell is unknown. In this study, we characterized the pattern of the human T cell receptor beta chain (TRB) and immunoglobulin heavy chain (IGH) complementarity-determining region 3 (CDR3) repertoires via high-throughput sequencing in 11 acute allograft rejection (AG) cases, 23 patients with stable allograft liver function (ST) who had liver transplantation performed and 20 healthy controls (HC). The diversity of TRB-CDR3 was significantly reduced in the AG group compared with the ST group and healthy controls (HC). The CDR3 and N-addition length distribution were not significantly different between the AG and ST groups. However, N-addition length distribution was significantly changed compared to HC. It seemed that AG used more short N-additions and healthy people used more long N-additions in TRB-CDR3 repertoire. Our findings suggested that the TRB-CDR3 region of AG had distinctive V gene use compared with that of HC. The characteristics of ST seemed to be in between those of AG and HC although the difference is not significant. Cluster analysis showed that the TRB repertoire could not effectively distinguish AG from ST. This research might give to a better understanding of the immune process of liver transplantation.


Assuntos
Regiões Determinantes de Complementaridade/imunologia , Rejeição de Enxerto/imunologia , Cadeias Pesadas de Imunoglobulinas/imunologia , Transplante de Fígado , Receptores de Antígenos de Linfócitos T alfa-beta/imunologia , Adulto , Regiões Determinantes de Complementaridade/genética , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Cadeias Pesadas de Imunoglobulinas/genética , Masculino , Pessoa de Meia-Idade , Receptores de Antígenos de Linfócitos T alfa-beta/genética
19.
J Pharm Biomed Anal ; 177: 112848, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31479998

RESUMO

Metabolic syndrome (MetS) is an important risk factor for type 2 diabetes, cardiovascular diseases and all-cause morbidity and mortality. Biomarkers can provide insight into the mechanism, facilitate early detection, and monitor progression of MetS and its response to therapeutic interventions. To identify potential biomarkers, we applied a non-targeted and targeted lipidomics method to characterize plasma metabolic profile in MetS patients. Metabolic profiling was performed on a non-target set (40 cases and 40 controls) on UHPLC-Q-TOF/MS and target set (80 MetS patients and 80 healthy controls) on UHPLC-Q-orbitrap MS. Using comprehensive screening and validation workflow, we identified a panel of three metabolites including PC(18:1/P-16:0), PC(o-22:3/22:3), PC(P-18:1/16:1). Our results indicated that the identified biomarkers may improve the risk prediction and provide a novel tool for monitoring of the progression of disease and response to treatment in MetS patients.


Assuntos
Metabolismo dos Lipídeos , Lipidômica/métodos , Síndrome Metabólica/diagnóstico , Fosfatidilcolinas/sangue , Adulto , Biomarcadores/sangue , Biomarcadores/metabolismo , Estudos de Casos e Controles , Cromatografia Líquida de Alta Pressão , Feminino , Humanos , Masculino , Síndrome Metabólica/metabolismo , Pessoa de Meia-Idade , Fosfatidilcolinas/metabolismo , Medição de Risco/métodos , Espectrometria de Massas em Tandem
20.
Chin J Integr Med ; 26(2): 106-113, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31385218

RESUMO

OBJECTIVE: To predict the chemical compositions and drug targets and to systematically dissect the pharmacological mechanism of Erxian Decoction (, EXD) as a treatment for premature ovarian failure (POF) using a systems pharmacology approach. METHODS: The compounds present in EXD were obtained from three databases. The active ingredient was identified by analyzing the values of oral bioavailability (OB), drug-likeness (DL), and Lipinski's rule (LR). The active ingredients were further searched in research articles, drug targets in the DrugBank database, and the C-T and T-P networks, as well as by pathway analysis using the Cytoscape platform. RESULTS: A total of 728 compounds were identified in EXD. Of these, 59 were identified as active compounds that conformed to the criteria with OB ⩾30% and DL ⩾0.18. By further searches in the literature, 126 related targets were identified that could interact with the active compounds. Additionally, it was found that the beneficial effects of EXD in POF are probably exerted via regulation of the immune system, modulation of estrogen levels, and anti-oxidative activities, and that it may act in a synergistic or cooperative manner with other therapeutic agents. CONCLUSIONS: The systems pharmacology approach is a comprehensive system that was used to elucidate the pharmacological mechanism of EXD as a treatment for POF. The results of this study will also facilitate the application of traditional medicine in modern treatment strategies.


Assuntos
Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Insuficiência Ovariana Primária/tratamento farmacológico , Feminino , Humanos , Mapeamento de Interação de Proteínas
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