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2.
Int J Biol Macromol ; 209(Pt B): 1784-1791, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35504416

RESUMO

The biosynthesis of brasilane-type sesquiterpenoids (BTSs) attracts much attention owing to their unique skeleton of 5/6 bicyclic structure that contains five Me groups. Here, the crystal structures of a BTS cyclase TaTC6 from Trichoderma atroviride FKI-3849 and its complexes with farnesyl pyrophosphate (FPP) and analogue were reported. These structural information reveal that TaTC6 exploits a hydrophobic pocket to constrain the hydrocarbon region of FPP in a "U-shape" to facilitate the initial C1-C11 bond formation after pyrophosphate ionization. Following, four carbocations of reaction intermediates were molecularly docked into the hydrophobic pocket to reveal critical residues involved in the cyclization cascade. Finally, an S239-stabilized water molecule that is 3.9 Å away from the C8 of the last allyl cation may conduct hydration to quench the reaction cascade. Mutating S239 to alanine led to ca. 40% reduction in activity compared with the wild-type enzyme. The conservation of the residues that constitute the hydrophobic pocket is also discussed. Overall, this study will give an insight into the mechanism of how the active site of STCs constrain the conformation of the flexible FPP and series allylic carbocations for the complicated-ring formation and unusual carbon rearrangement in the biosynthesis of BTSs.

3.
Anal Bioanal Chem ; 2022 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-35538228

RESUMO

The fates of nanomaterials (NMs) in vivo are greatly dependent on their interactions with human serum proteins. However, the interfacial molecular details of NMs-serum proteins are still difficult to be probed. Herein, the molecular interaction details of human serum albumin (HSA) with Au and SiO2 nanoparticles have been systematically interrogated and compared by using lysine reactivity profiling mass spectrometry (LRP-MS). We demonstrated the biocompatibility of Au is better than SiO2 nanoparticles and the NMs surface charge state played a more important role than particle size in the combination of NMs-HSA at least in the range of 15-40 nm. Our results will contribute to the fundamental mechanism understanding of NMs-serum protein interactions as well as the NMs rational design.

4.
Phys Rev Lett ; 128(16): 162301, 2022 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-35522484

RESUMO

The production of J/ψ mesons in heavy-ion collisions at the Large Hadron Collider is believed to be dominated by the recombination of charm and anticharm quarks in a hot QCD medium. However, measurements of the elliptic flow (v_{2}) of J/ψ mesons in these reactions are not well described by existing calculations of J/ψ recombination for transverse momenta p_{T}≳4 GeV. We revisit these calculations in two main aspects. Employing the resonance recombination model, we implement distribution functions of charm quarks transported through the quark-gluon plasma using state-of-the-art Langevin simulations and account for the space-momentum correlations of the diffusing charm and anticharm quarks in a hydrodynamically expanding fireball. This extends the relevance of the recombination processes to substantially larger momenta than before. We also revisit the suppression of primordially produced J/ψ's by propagating them through the same hydrodynamic medium, leading to a marked increase of their v_{2} over previous estimates. Combining these developments into a calculation of the p_{T}-dependent nuclear modification factor and v_{2} of inclusive J/ψ production in semicentral Pb-Pb collisions at the LHC, we find a good description of the experimental results by the ALICE Collaboration. Our results thus resolve the abovementioned v_{2} puzzle and imply the relevance of recombination processes for p_{T}'s of up to ∼8 GeV.

5.
Int J Gen Med ; 15: 3991-4006, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35437352

RESUMO

Background: Lung squamous cell carcinoma (LUSC) is a malignant tumour of the lung epithelium. A hypoxic environment can promote tumour cell proliferation and invasion. Therefore, this study aims to explore hypoxia-related genes and construct reliable models to predict the prognosis, cellular processes, immune microenvironment and target compounds of lung squamous carcinoma. Methods: The transcriptome data and matched clinical information of LUSC were retrieved from The Cancer Genome Atlas (TCGA) database. The GSVA algorithm calculated each LUSC patient's hypoxia score, and all LUSC patients were divided into the high hypoxia score group and low hypoxia score group. Weighted gene co-expression network analysis (WGCNA) and differential expression analysis were performed to screen out differentially expressed hypoxia-related genes (DE-HRGs) in LUSC microenvironment, and the underlying regulatory mechanism of DE-HRGs in LUSC was explored through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Hereafter, we established a prognosis-related genetic signature for DE-HRGs using univariate and multivariate Cox regression analyses. The relationship between gene signature and immune cells was further evaluated. Finally, the Comparative Toxicogenomics Database (CTD) was utilized to predict the targeted drugs for the prognostic genes. Results: We obtained 376 DE-HRGs. Functional enrichment analysis indicated that the DE-HRGs were involved in the cell cycle-related regulatory processes. Next, we developed and validated 3 HRGs-based prognostic signature for LUSC, including HELLS, GPRIN1, and FAM83A. Risk score is an independent prognostic factor for LUSC. Functional enrichment analysis and immune landscape analysis suggested that the risk scoring system might be involved in altering the immune microenvironment of LUSC patients to influence patient outcomes. Ultimately, a total of 92 potential compounds were predicted for the three prognostic genes. Conclusion: In summary, we developed and validated a hypoxia-related model for LUSC, reflecting the cellular processes and immune microenvironment characteristics and predicting the prognostic outcomes and targeted compounds.

6.
Eur J Med Res ; 27(1): 58, 2022 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-35462555

RESUMO

BACKGROUND: In this study, we attempted to assess the efficacy and safety of acupuncture for allergic rhinitis (AR), and to test the robustness of the estimated effects. METHODS: The Cochrane methodology standard was followed to conduct this systematic review. Randomized controlled trials (RCTs) comparing acupuncture with other therapies for AR were included. Furthermore, trial sequential analysis was conducted to test the robustness of pooled results. Thirty trials with 4413 participants were included. RESULTS: Acupuncture improved the nasal symptoms on Total Nasal Symptom Score (TNSS) and quality of life measured by Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) in adults with AR, compared to acupuncture with no intervention. Acupuncture was also shown to be more effective than sham acupuncture for nasal symptom (RQLQ subscale, n = 489, MD - 0.60, 95% CI - 1.16 to - 0.04) and quality of life (RQLQ, n = 248, - 8.47 95% CI - 14.91, - 2.03). No clear difference was observed between acupuncture and cetirizine or loratadine. Interestingly, trial sequential analysis (TSA) failed to confirm the aforementioned results. The effect of acupuncture for children/adolescents with AR remains unclear due to insufficient data. The performance bias and attrition bias are serious in most studies that were included. Selection bias may also have affected the quality of the evidence. CONCLUSION: Acupuncture may have an advantage over no intervention and sham acupuncture in improving nasal symptoms and quality of life for adults with AR. The effect of acupuncture and cetirizine or loratadine for AR may be similar. Additional trials are necessary to confirm these results.


Assuntos
Terapia por Acupuntura , Rinite Alérgica , Terapia por Acupuntura/métodos , Adolescente , Adulto , Cetirizina , Criança , Humanos , Loratadina , Qualidade de Vida , Rinite Alérgica/terapia , Inquéritos e Questionários
7.
Neuropsychiatr Dis Treat ; 18: 659-667, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35378822

RESUMO

Background: Patients suffered aneurysmal subarachnoid hemorrhage (aSAH) usually develop poor survival and functional outcome. Evaluating aSAH patients at high risk of poor outcome is necessary for clinicians to make suitable therapeutical strategy. This study is conducted to develop prognostic model using XGBoost (extreme gradient boosting) algorithm in aSAH. Methods: A total of 351 aSAH patients admitted to West China hospital were identified. Patients were divided into training set and test set with ratio of 7:3 to testify the predictive value of XGBoost based prognostic model. Additionally, logistic regression model was also constructed and compared with XGBoost based model. Area under the receiver operating characteristic curve (AUC), sensitivity and specificity were calculated to evaluate the value of XGBoost and logistic regression. Results: There were 74 (21.1%) non-survivors and 148 (42.1%) patients with unfavorable functional outcome. Non-survivors had older age (p=0.025), lower Glasgow coma scale (GCS) (p<0.001), higher World Federation of Neurosurgical Societies WFNS score (p<0.001), mFisher score (p<0.001). The incidence of intraventricular hemorrhage (IVH) (p=0.025) and delayed cerebral ischemia (DCI) (p<0.001) was higher in non-survivors than survivors. The AUC of XGBoost model for predicting mortality and unfavorable functional outcome were 0.950 and 0.958, which were higher than 0.767 and 0.829 of logistic regression model. Conclusion: XGBoost based model is more precise than logistic regression model in predicting outcome of aSAH patients. Using XGBoost prognostic model is helpful for clinicians to identify high-risk aSAH patients and therefore strengthen medical care.

8.
Front Neurol ; 13: 662385, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35432157

RESUMO

Background: Traumatic brain injury (TBI) is a serious public health issue all over the world. This study was designed to evaluate the prognostic value of lactate to albumin ratio (LAR) on patients with moderate to severe TBI. Methods: Clinical data of 273 moderate to severe TBI patients hospitalized in West China Hospital between May 2015 and January 2018 were collected. Multivariate logistic regression analyses were used to explore risk factors and construct a prognostic model of in-hospital mortality in this cohort. A receiver operating characteristic (ROC) curve was drawn to evaluate the discriminative ability of this model. Results: Non-survivors had higher LAR than survivors (1.09 vs. 0.53, p < 0.001). Results of multivariate logistic regression analysis showed that Glasgow Coma Scale (GCS; odds ratio [OR] = 0.743, p = 0.001), blood glucose (OR = 1.132, p = 0.005), LAR (OR = 1.698, p = 0.022), subdural hematoma (SDH; OR = 2.889, p = 0.006), intraparenchymal hemorrhage (IPH; OR = 2.395, p = 0.014), and diffuse axonal injury (DAI; OR = 2.183, p = 0.041) were independent risk factors of in-hospital mortality in included patients. These six factors were utilized to construct the prognostic model. The area under the ROC curve (AUC) values of single lactate, albumin, and LAR were 0.733 (95% Cl; 0.673-0.794), 0.740 (95% Cl; 0.683-0.797), and 0.780 (95% Cl; 0.725-0.835), respectively. The AUC value of the prognostic model was 0.857 (95%Cl; 0.812-0.901), which was higher than that of LAR (Z = 2.1250, p < 0.05). Conclusions: Lactate to albumin ratio is a readily available prognostic marker of moderate to severe TBI patients. A prognostic model incorporating LAR is beneficial for clinicians to evaluate possible progression and make treatment decisions in TBI patients.

9.
Comput Math Methods Med ; 2022: 1527159, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35432583

RESUMO

Alzheimer's disease (AD) is a brain illness that affects learning and memory capacities over time. In recent investigations, acupuncture has been shown to be an effective alternative treatment for AD. We investigated the effect of acupuncture on learning and memory abilities using a water maze in APP/PS1 transgenic mice. The amounts of Aß and tau protein in mice's hippocampal tissue were determined using Western blot. The levels of IL-1ß, IL-10, LPS and TNF-α in mice's serum were measured using ELISA. The variations of gut microbiota in mice's feces were determined using the 16SrDNA technique, and the metabolites were examined using a untargeted metabolomics methodology. The results showed that acupuncture treatment improved mice's learning and memory abilities substantially. Acupuncture therapy regulated the Aß and tau protein concentration as well as the levels of IL-10 and LPS. Acupuncture treatment influenced the mouse microbiota and metabolites and had been linked to six biochemical pathways. This study adds to our understanding of the effect of acupuncture on AD and opens the door to further research into the alterations of intestinal bacteria in the presence of AD.


Assuntos
Terapia por Acupuntura , Doença de Alzheimer , Microbioma Gastrointestinal , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Doença de Alzheimer/terapia , Peptídeos beta-Amiloides/metabolismo , Peptídeos beta-Amiloides/farmacologia , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Precursor de Proteína beta-Amiloide/farmacologia , Animais , Modelos Animais de Doenças , Microbioma Gastrointestinal/fisiologia , Humanos , Interleucina-10/farmacologia , Lipopolissacarídeos , Aprendizagem em Labirinto , Camundongos , Camundongos Transgênicos , Proteínas tau/genética
10.
Environ Pollut ; 304: 119240, 2022 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-35367504

RESUMO

The fungal species Fusarium can cause devastating disease in agricultural crops. Phenamacril is an extremely specific cyanoacrylate fungicide and a strobilurine analog that has excellent efficacy against Fusarium. To date, information on the mechanisms involved in the uptake, accumulation, and metabolism of phenamacril in plants is scarce. In this study, lettuce and radish were chosen as model plants for a comparative analysis of the absorption, accumulation, and metabolic characteristics of phenamacril from a polluted environment. We determined the total amount of phenamacril in the plant-water system by measuring the concentrations in the solution and plant tissues at frequent intervals over the exposure period. Phenamacril was readily taken up by the plant roots with average root concentration factor ranges of 60.8-172.7 and 16.4-26.9 mL/g for lettuce and radish, respectively. However, it showed limited root-to-shoot translocation. The lettuce roots had a 2.8-12.4-fold higher phenamacril content than the shoots; whereas the radish plants demonstrated the opposite, with the shoots having 1.5 to 10.0 times more phenamacril than the roots. By the end of the exposure period, the mass losses from the plant-water systems reached 72.0% and 66.3% for phenamacril in lettuce and radish, respectively, suggesting evidence of phenamacril biotransformation. Further analysis confirmed that phenamacril was metabolized via hydroxylation, hydrolysis of esters, demethylation, and desaturation reactions, and formed multiple transformation products. This study furthers our understanding of the fate of phenamacril when it passes from the environment to plants and provides an important reference for its scientific use and risk assessment.


Assuntos
Fungicidas Industriais , Raphanus , Produtos Agrícolas , Cianoacrilatos/metabolismo , Cianoacrilatos/farmacologia , Fungicidas Industriais/metabolismo , Alface/metabolismo , Raízes de Plantas/metabolismo , Raphanus/metabolismo , Água/metabolismo
13.
BMC Gastroenterol ; 22(1): 200, 2022 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-35448976

RESUMO

BACKGROUND: Gallbladder cancer is associated with late diagnosis and poor prognosis. Current study aims to develop a prognostic nomogram for predicting survival of gallbladder cancer patients after surgery. METHODS: Two large cohorts were included in this analysis. One consisted of 1753 gallbladder cancer patients from the Surveillance, Epidemiology, and End Results (SEER) database, and the other consisted of 239 patients from Shanghai Renji hospital. Significant prognostic factors were identified and integrated to develop the nomogram. Then the model was subjected to bootstrap internal validation and external validation. RESULTS: Univariate and multivariate analysis indicated that age, tumor histology, T-stage, N-stage and M-stage were significant prognostic factors, which were all included to build the nomogram. The model showed good discrimination, with a concordance index (C-index) of 0.724 (95% CI, 0.708-0.740), and good calibration. Application of the nomogram in the validation cohort still presented good discrimination (C-index, 0.715 [95% CI 0.672-0.758]) and good calibration. In the primary cohort, the C-index of the nomogram was 0.724, which was significantly higher than the Nevin staging system (C-index = 0.671; P < 0.001) and the 8th TNM staging system (C-index = 0.682; P < 0.001). In the validation cohort, the C-index of the nomogram was 0.715, which was also higher than the Nevin staging system (C-index = 0.692; P < 0.05) and the 8th TNM staging system (C-index = 0.688; P = 0.06). CONCLUSIONS: The proposed nomogram resulted in more-accurate prognostic prediction for patients with gallbladder cancer after surgery.


Assuntos
Neoplasias da Vesícula Biliar , Nomogramas , China , Neoplasias da Vesícula Biliar/cirurgia , Humanos , Estadiamento de Neoplasias , Prognóstico , Programa de SEER
14.
Int J Gen Med ; 15: 3739-3751, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35418779

RESUMO

Background: Inducible co-stimulator (ICOS) is a cell-enhanced co-stimulatory receptor that has shown great potential in the regulation of innate and adaptive immunity. However, the role of ICOS in lung adenocarcinoma (LUAD) remains unclear. Methods: We used data from the Cancer Genome Atlas(TCGA) database to identify the expression and prognostic role of ICOS in LUAD. The results were validated using Gene Expression Omnibus(GEO) and Kaplan-Meier plotter databases. A model with predictive performance for overall survival of LUAD patients was constructed using fitted ICOS expression and other clinical parameters. We explored the biological function of ICOS. Subsequently, we further analysed and validated the effect of ICOS expression on tumour immune microenvironment (TIME) and survival. Finally, the CellMiner database was used to determine the relationship between ICOS expression and drug sensitivity. Results: ICOS expression is significantly associated with poor prognosis in multiple cancers, especially LUAD, and is a good predictor of overall survival in LUAD patients. The biological function is to promote autoimmunity and inhibit cell proliferation. ICOS-related survival prediction model developed to more accurately predict 1-, 3- and 5-year survival probabilities for LUAD patients. In addition, we can use the expression of ICOS to effectively assess patient malignancy, prognosis, TIME status and clinical combination of drugs. Conclusion: Our results suggest that ICOS is correlated with prognosis and immune infiltrating levels in LUAD. Higher ICOS expression predicts better TIME. This study provides a novel strategy for the development of immunotherapeutic and prognostic markers in LUAD.

15.
Eur J Med Chem ; 237: 114397, 2022 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-35472851

RESUMO

2-(2-Phenylethyl)chromones (PECs) are a group of naturally occurring compounds, which are characterized as phenylethyl substituent at the C2 position of chromone. They have been isolated mainly from Aquilaria sinensis (Lour.) Gilg. This type of natural compound is correlative with anti-diabetes, anticancer, antioxidant, antibacterial, anticancer, and anti-inflammatory activities. Due to the versatile activities of PECs, more and more researchers use different improved methods to synthesize them and their derivatives. This review mainly focuses on the natural occurrence, chemical synthesis, and biological activities of PECs, which were published up until 2020.

16.
J Environ Sci (China) ; 114: 233-248, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35459489

RESUMO

The conventional Ensemble Kalman filter (EnKF), which is now widely used to calibrate emission inventories and to improve air quality simulations, is susceptible to simulation errors of meteorological inputs, making accurate updates of high temporal-resolution emission inventories challenging. In this study, we developed a novel meteorologically adjusted inversion method (MAEInv) based on the EnKF to improve daily emission estimations. The new method combines sensitivity analysis and bias correction to alleviate the inversion biases caused by errors of meteorological inputs. For demonstration, we used the MAEInv to inverse daily carbon monoxide (CO) emissions in the Pearl River Delta (PRD) region, China. In the case study, 60% of the total CO simulation biases were associated with sensitive meteorological inputs, which would lead to the overestimation of daily variations of posterior emissions. Using the new inversion method, daily variations of emissions shrank dramatically, with the percentage change decreased by 30%. Also, the total amount of posterior CO emissions estimated by the MAEInv decreased by 14%, indicating that posterior CO emissions might be overestimated using the conventional EnKF. Model evaluations using independent observations revealed that daily CO emissions estimated by MAEInv better reproduce the magnitude and temporal patterns of ambient CO concentration, with a higher correlation coefficient (R, +37.0%) and lower normalized mean bias (NMB, -17.9%). Since errors of meteorological inputs are major sources of simulation biases for both low-reactive and reactive pollutants, the MAEInv is also applicable to improve the daily emission inversions of reactive pollutants.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Poluição do Ar/prevenção & controle , Monóxido de Carbono/análise , China , Monitoramento Ambiental/métodos , Rios
17.
Toxicol In Vitro ; 82: 105367, 2022 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-35476924

RESUMO

Benzophenones are widely used in industry and commonly added in many personal care products. However, the neurotoxicity, in particular neurodevelopmental toxicity, of benzophenone family chemicals and metabolites has not been fully elucidated. Our recent mechanistic study in mice showed that early life exposure to a major benzophenone metabolite, 4-hydroxybenzophenone (4HBP), disrupted endoplasmic reticulum (ER) proteostasis and evoked inflammatory response in hippocampal neural stem cells (NSCs), leading to cognitive dysfunction. Despite so, detailed inflammatory cytokine(s) that possibly mediate this toxicity remains to be defined and validated. In this study, we confirmed that 4HBP treatment inhibited the viability and sphere growth of mouse NSCs in vitro. Importantly, re-interrogation of the transcriptomic data of NSCs treated with 4HBP identified the top upregulated genes, wherein the chemokine Cxcl1 ranked first. Immunofluorescent staining and qRT-PCR validated the robust induction of Cxcl1 on the protein and mRNA levels upon 4HBP treatment. Furthermore, siRNA-mediated knockdown of Cxcl1 transiently blocked its expression and led to enhanced NSCs viability in the presence of 4HBP. Together, these in vitro results indicated that the adverse effect of benzophenones on NSCs is mediated, at least in part, by induction of the chemokine Cxcl1.

18.
World Neurosurg ; 2022 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-35430400

RESUMO

BACKGROUND: Traumatic brain injury (TBI) brings severe mortality and morbidity risk to patients. Predicting the outcome of these patients is necessary for physicians to make suitable treatments to improve prognosis. The aim of this study is to develop a mortality prediction approach using XGBoost (extreme gradient boosting) in moderate-to-severe TBI. METHODS: A total of 368 patients hospitalized in West China hospital for TBI with Glasgow Coma Scale (GCS) below 13 were identified. To construct the XGBoost prediction approach, patients were divided into training set and test set with a ratio of 7:3. A logistic regression prediction model was also constructed and compared with the XGBoost model. Area under the receiver operating characteristic curve, accuracy, sensitivity, and specificity were calculated to compare the prognostic value between XGBoost and logistic regression. RESULTS: A total of 205 patients suffered a poor outcome with a mortality of 55.7%. Nonsurvivors had a lower GCS (5 vs. 7, P < 0.001) and a higher Injury Severit Score (ISS) than survivors (25 vs. 16, P < 0.001). Platelet (P < 0.001), albumin (P < 0.001), and hemoglobin (P < 0.001) were significantly lower in nonsurvivors, whereas glucose (P < 0.001) and prothrombin time (P < 0.001) were significantly higher in nonsurvivors. Among the XGBoost approach, GCS, prothrombin time, and glucose had the most significant feature importance. The area under the receiver operating characteristic curve (0.955 vs. 0.805) and accuracy (0.955 vs. 0.70) of XGBoost were both higher than logistic regression. CONCLUSION: Predicting mortality of patients with moderate-to-severe TBI using the XGBoost algorism is more effective and precise than logistic regression. The XGBoost prediction approach is beneficial for physicians to evaluate patients with TBI at high risk of poor outcome.

19.
Front Med (Lausanne) ; 9: 787770, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35295596

RESUMO

Background: Tissue covalently closed circular DNA (cccDNA) can reflect the activity of HBV replication. However, it is impractical to assess intrahepatic cccDNA in every outpatient. Serum pregenome RNA (pgRNA) is transcribed from intrahepatic cccDNA and may reflect the activity of intrahepatic cccDNA. We explored the dynamics and the potential role of serum pgRNA in patients receiving long-term NAs treatment. Methods: Serum pgRNA, HBV DNA, HBsAg, HBeAg, and ALT levels were quantified, and the relationships between serum pgRNA and these common clinical indicators before and after the treatment were investigated. Results: Serum pgRNA showed dynamic change during the 96-month NAs therapy, and serum pgRNA levels were positive and detectable in 19 patients with undetectable serum HBV DNA. Serum pgRNA showed strong and positive correlation with serum HBV DNA (r = 0.693, p < 0.001) and serum HBsAg levels (r = 0.621, p < 0.001) at baseline. Patients with HBeAg seroconversion had lower baseline serum pgRNA levels (p = 0.002). The area under the curve (AUC) of baseline serum pgRNA for predicting HBeAg seroconversion was 0.742 (95% CI: 0.606-0.850) with 63.16% sensitivity and 80.56% specificity. The cumulative HBeAg seroconversion rate was higher in patients with low serum pgRNA (p = 0.001). Conclusion: Serum pgRNA of low level at baseline or great decline at month 6 may independently predict the high incidence of undetectable serum pgRNA at year 4 following NAs therapy, and the baseline serum pgRNA may serve as a novel predictor for HBeAg seroconversion during NAs therapy.

20.
Pharm Biol ; 60(1): 729-742, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35352622

RESUMO

CONTEXT: The potential anti-inflammatory bioactivities of ß-hydroxyisovalerylshikonin (ß-HIVS) remain largely unknown. OBJECTIVE: This study investigated the anti-inflammatory effects and underlying mechanisms of ß-HIVS. MATERIALS AND METHODS: RAW 264.7 cells stimulated with LPS (100 ng/mL) for 24 h were treated with the non-cytotoxic doses of ß-HIVS (0.5 or 1 µM, determined by MTT and Trypan blue staining), qRT-PCR and FCM assay were used to examine macrophage polarization transitions. Western blotting was used to evaluate the activation of the AMPK/Nrf2 pathway. In vivo, C57BL/6 mice were randomly divided into vehicle control, LPS (10 mg/kg), and ß-HIVS (2.5 mg/kg) combined with LPS (10 mg/kg) groups, blood samples, BALF, and lung tissues of mice were subjected to ELISA, qRT-PCR, FCM, and H&E staining. RESULTS: ß-HIVS (1 µM) inhibited LPS-induced expression of M1 macrophage markers (TNF-α: 0.29-fold, IL-1ß: 0.32-fold), promoted the expression of M2 macrophage markers (CD206: 3.14-fold, Arginase-1: 3.98-fold) in RAW 264.7 cells; mechanistic studies showed that ß-HIVS increased the expression of nuclear Nrf2 (2.04-fold) and p-AMPK (3.65-fold) compared with LPS group (p < 0.05). In vivo, ß-HIVS decreased the levels of pro-inflammatory cytokines (TNF-α: 1130.41 vs. 334.88 pg/mL, IL-1ß: 601.89 vs. 258.21 pg/mL in serum; TNF-α: 893.07 vs. 418.21 pg/mL, IL-1ß: 475.22 vs. 298.54 pg/mL in BALF), decreased the proportion of M1 macrophages (77.83 vs. 68.53%) and increased the proportion of M2 macrophages (13.55 vs. 19.56%) in BALF, and reduced lung tissue damage and septic mice survival (p < 0.05). CONCLUSIONS: These results indicate that ß-HIVS may be a new potential anti-inflammatory agent.


Assuntos
Fator 2 Relacionado a NF-E2 , Sepse , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Lipopolissacarídeos/farmacologia , Macrófagos , Camundongos , Camundongos Endogâmicos C57BL , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Naftoquinonas , Sepse/tratamento farmacológico , Sepse/metabolismo
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