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1.
Front Oncol ; 14: 1359925, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38835373

RESUMO

Objective: To evaluate the value of the malignant subregion-based texture analysis in predicting Ki-67 status in breast cancer. Materials and methods: The dynamic contrast-enhanced magnetic resonance imaging data of 119 histopathologically confirmed breast cancer patients (81 patients with high Ki-67 expression status) from January 2018 to February 2023 in our hospital were retrospectively collected. According to the enhancement curve of each voxel within the tumor, three subregions were divided: washout subregion, plateau subregion, and persistent subregion. The washout subregion and the plateau subregion were merged as the malignant subregion. The texture features of the malignant subregion were extracted using Pyradiomics software for texture analysis. The differences in texture features were compared between the low and high Ki-67 expression cohorts and then the receiver operating characteristic (ROC) curve analysis to evaluate the predictive performance of texture features on Ki-67 expression. Finally, a support vector machine (SVM) classifier was constructed based on differential features to predict the expression level of Ki-67, the performance of the classifier was evaluated using ROC analysis and confirmed using 10-fold cross-validation. Results: Through comparative analysis, 51 features exhibited significant differences between the low and high Ki-67 expression cohorts. Following feature reduction, 5 features were selected to build the SVM classifier, which achieved an area under the ROC curve (AUC) of 0.77 (0.68-0.87) for predicting the Ki-67 expression status. The accuracy, sensitivity, and specificity were 0.76, 0.80, and 0.68, respectively. The average AUC from the 10-fold cross-validation was 0.72 ± 0.14. Conclusion: The texture features of the malignant subregion in breast cancer were potential biomarkers for predicting Ki-67 expression level in breast cancer, which might be used to precisely diagnose and guide the treatment of breast cancer.

2.
EClinicalMedicine ; 72: 102622, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38745965

RESUMO

Background: The role of transarterial chemoembolization (TACE) in the treatment of advanced hepatocellular carcinoma (HCC) is unconfirmed. This study aimed to assess the efficacy and safety of immune checkpoint inhibitors (ICIs) plus anti-vascular endothelial growth factor (anti-VEGF) antibody/tyrosine kinase inhibitors (TKIs) with or without TACE as first-line treatment for advanced HCC. Methods: This nationwide, multicenter, retrospective cohort study included advanced HCC patients receiving either TACE with ICIs plus anti-VEGF antibody/TKIs (TACE-ICI-VEGF) or only ICIs plus anti-VEGF antibody/TKIs (ICI-VEGF) from January 2018 to December 2022. The study design followed the target trial emulation framework with stabilized inverse probability of treatment weighting (sIPTW) to minimize biases. The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), objective response rate (ORR), and safety. The study is registered with ClinicalTrials.gov, NCT05332821. Findings: Among 1244 patients included in the analysis, 802 (64.5%) patients received TACE-ICI-VEGF treatment, and 442 (35.5%) patients received ICI-VEGF treatment. The median follow-up time was 21.1 months and 20.6 months, respectively. Post-application of sIPTW, baseline characteristics were well-balanced between the two groups. TACE-ICI-VEGF group exhibited a significantly improved median OS (22.6 months [95% CI: 21.2-23.9] vs 15.9 months [14.9-17.8]; P < 0.0001; adjusted hazard ratio [aHR] 0.63 [95% CI: 0.53-0.75]). Median PFS was also longer in TACE-ICI-VEGF group (9.9 months [9.1-10.6] vs 7.4 months [6.7-8.5]; P < 0.0001; aHR 0.74 [0.65-0.85]) per Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. A higher ORR was observed in TACE-ICI-VEGF group, by either RECIST v1.1 or modified RECIST (41.2% vs 22.9%, P < 0.0001; 47.3% vs 29.7%, P < 0.0001). Grade ≥3 adverse events occurred in 178 patients (22.2%) in TACE-ICI-VEGF group and 80 patients (18.1%) in ICI-VEGF group. Interpretation: This multicenter study supports the use of TACE combined with ICIs and anti-VEGF antibody/TKIs as first-line treatment for advanced HCC, demonstrating an acceptable safety profile. Funding: National Natural Science Foundation of China, National Key Research and Development Program of China, Jiangsu Provincial Medical Innovation Center, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, and Nanjing Life Health Science and Technology Project.

3.
Plant Biotechnol J ; 22(5): 1417-1432, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38193234

RESUMO

Root architecture and function are critical for plants to secure water and nutrient supply from the soil, but environmental stresses alter root development. The phytohormone jasmonic acid (JA) regulates plant growth and responses to wounding and other stresses, but its role in root development for adaptation to environmental challenges had not been well investigated. We discovered a novel JA Upregulated Protein 1 gene (JAUP1) that has recently evolved in rice and is specific to modern rice accessions. JAUP1 regulates a self-perpetuating feed-forward loop to activate the expression of genes involved in JA biosynthesis and signalling that confers tolerance to abiotic stresses and regulates auxin-dependent root development. Ectopic expression of JAUP1 alleviates abscisic acid- and salt-mediated suppression of lateral root (LR) growth. JAUP1 is primarily expressed in the root cap and epidermal cells (EPCs) that protect the meristematic stem cells and emerging LRs. Wound-activated JA/JAUP1 signalling promotes crosstalk between the root cap of LR and parental root EPCs, as well as induces cell wall remodelling in EPCs overlaying the emerging LR, thereby facilitating LR emergence even under ABA-suppressive conditions. Elevated expression of JAUP1 in transgenic rice or natural rice accessions enhances abiotic stress tolerance and reduces grain yield loss under a limited water supply. We reveal a hitherto unappreciated role for wound-induced JA in LR development under abiotic stress and suggest that JAUP1 can be used in biotechnology and as a molecular marker for breeding rice adapted to extreme environmental challenges and for the conservation of water resources.


Assuntos
Ciclopentanos , Oryza , Oxilipinas , Oryza/genética , Oryza/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Melhoramento Vegetal , Reguladores de Crescimento de Plantas/metabolismo , Regulação da Expressão Gênica de Plantas/genética
4.
Hepatol Int ; 18(1): 4-31, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37864725

RESUMO

Hepatocellular carcinoma (HCC) is one of the most common malignancies and the third leading cause of cancer-related deaths globally. Hepatic arterial infusion chemotherapy (HAIC) treatment is widely accepted as one of the alternative therapeutic modalities for HCC owing to its local control effect and low systemic toxicity. Nevertheless, although accumulating high-quality evidence has displayed the superior survival advantages of HAIC of oxaliplatin, fluorouracil, and leucovorin (HAIC-FOLFOX) compared with standard first-line treatment in different scenarios, the lack of standardization for HAIC procedure and remained controversy limited the proper and safe performance of HAIC treatment in HCC. Therefore, an expert consensus conference was held on March 2023 in Guangzhou, China to review current practices regarding HAIC treatment in patients with HCC and develop widely accepted statements and recommendations. In this article, the latest evidence of HAIC was systematically summarized and the final 22 expert recommendations were proposed, which incorporate the assessment of candidates for HAIC treatment, procedural technique details, therapeutic outcomes, the HAIC-related complications and corresponding treatments, and therapeutic scheme management.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Resultado do Tratamento , Artéria Hepática/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Fluoruracila/uso terapêutico , Infusões Intra-Arteriais
5.
Bioorg Chem ; 143: 107022, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38142558

RESUMO

Liver fibrosis remains a global health challenge due to its rapidly rising prevalence and limited treatment options. The orphan nuclear receptor Nur77 has been implicated in regulation of autophagy and liver fibrosis. Targeting Nur77-mediated autophagic flux may thus be a new promising strategy against hepatic fibrosis. In this study, we synthesized four types of Nur77-based thiourea derivatives to determine their anti-hepatic fibrosis activity. Among the synthesized thiourea derivatives, 9e was the most potent inhibitor of hepatic stellate cells (HSCs) proliferation and activation. This compound could directly bind to Nur77 and inhibit TGF-ß1-induced α-SMA and COLA1 expression in a Nur77-dependent manner. In vivo, 9e significantly reduced CCl4-mediated hepatic inflammation response and extracellular matrix (ECM) production, revealing that 9e is capable of blocking the progression of hepatic fibrosis. Mechanistically, 9e induced Nur77 expression and enhanced autophagic flux by inhibiting the mTORC1 signaling pathway in vitro and in vivo. Thus, the Nur77-targeted lead 9e may serve as a promising candidate for treatment of chronic liver fibrosis.


Assuntos
Antifibróticos , Tiossemicarbazonas , Humanos , Tiossemicarbazonas/metabolismo , Células Estreladas do Fígado , Fígado/metabolismo , Cirrose Hepática/metabolismo , Tioureia/metabolismo , Tetracloreto de Carbono
6.
Herald of Medicine ; (12): 167-174, 2024.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1023694

RESUMO

Objective To study the effect of curcumin on wound healing in diabetic mice.Methods The effect of curcumin on fibroblast activity was examined by the MTT assay,and the ROS detection kit was used to detect the effect of curcumin on the hydrogen peroxide-induced scavenging effect of reactive oxygen species(ROS)in fibroblasts.Q-PCR was used to detect the effects of curcumin on the mRNA expression of inflammatory factors CD86,CD206,IL-6 and ARG1 in lipopolysaccharide-induced RAW 264.7macrophage.The wound model of diabetes was established by intraperitoneal injection of streptozotocin.Hematoxylin-eosin(HE)and Masson staining were used to evaluate wound healing and histomorphological changes,and immunofluorescence staining was used to determine skin tissue α-smooth muscle actin,CD86 and CD206 expression.Results Curcumin had no significant effect on fibroblast activity at concentrations less than 20 mol·L-1;curcumin scavenged hydrogen peroxide-induced intracellular ROS in fibroblasts;curcumin decreased the mRNA expression of CD86 and IL-6 while increasing CD206 and ARG1 in lipopolysaccharide-induced RAW 264.7 macrophages.After in vivo administration,compared with the control group,wound healing was significantly faster in the curcumin(15,30 mg·mL-1)group after 7 d and 14 d of wound perforation(P<0.01).Hematoxylin-eosin(HE)and Masson staining results confirmed a significant increase in granulation tissue and a significant increase in collagen deposition in the curcumin(15,30 mg·mL-1)group.Immunofluorescence assay showed significantly higher expression of CD206(P<0.01)and significantly reduced expression of CD86(P<0.01)in the skin wounds of curcumin(15,30 mg·mL-1)for 14 d.In addition,the expression of α-SMA in the wound of the high-dose curcumin(30 mg·mL-1)group was significantly higher than that of the low-dose curcumin group(P<0.01).Conclusion Curcumin accelerates diabetic wound healing by promoting granulation tissue proliferation and collagen deposition in refractory diabetic wounds in mice through its anti-inflammatory and antioxidant effects.

7.
Chinese Journal of Zoonoses ; (12): 46-55, 2024.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1024888

RESUMO

To understand Helicobacter pylori's drug resistance,genetic diversity,and relationship with clinical diseases in the Guiyang and Qiannan minority areas of Guizhou Province,we collected samples through endoscopy,and isolated and cul-tured H.pylori.The drug resistance and genotype characteristics were determined.The differences in different regions and dis-ease types were compared,and the structural characteristics of H.pylori and mixed infections with different strains of H.py-lori in Qiannan Prefecture were analyzed.A difference in the composition ratio of EPYIA typing in the cagA variable region was observed between the two areas(P=0.012),and the composition ratio of the vacA genotype differed(P=0.000).A total of 94.6%(53/56)new sequences of H.pylori strains from two regions were obtained by MLST.The rate of infection by H.pylori mixed with different strains was 44.4%in Qiannan Pre-fecture,and no significant difference was observed in the com-position of H.pylori mixed infections among patients with dif-ferent clinical diseases(P=0.349).Differences in EPI YA typ-ing and the vacA genotype composition ratio in the cagA varia-ble region of H.pylori were observed between the Qiannan Prefecture and Guiyang City.

8.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1031091

RESUMO

Breastfeeding is the best natural food for infants. In infants with congenital heart disease(CHD), breast milk can reduce the incidence of necrotizing enterocolitis, feeding intolerance and growth failure, and improve the overall prognosis. However, there are many obstacles to breastfeeding in infants with CHD as well as lack of related domestic research. This study mainly focuses on breastfeeding status, influencing factors, assessment, implementation and solutions for the infants with CHD, and proposed the future research recommendations on clinical practices, in order to provide reference for the breastfeeding management of infants with CHD in China.

9.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1032188

RESUMO

Objective @#To employ the EQ-5D-5L questionnaire to evaluate HRQOL in patients on peritoneal dialysis ( PD) and investigate the related risk factors to provide suggestions for improving quality of life.@*Methods @# PD patients who were followed up regularly in the department of nephrology were recruited in this study. Demographic characteristics and laboratory data were collected.Exercise capacity was assessed by the 6-MWT.PHQ-9 was con- ducted to screen depression status.The EQ-5D-5L questionnaire was used to evaluate HRQOL.Multivariate linear regression analysis was used to examine the potential influencing factors of EQ-5D-5L health utility value.@*Results @#The highest health utility value of EQ-5D-5L was 1 point,while the lowest was -0. 01 points.The mean EQ-5D-5L score was (0. 92 ± 0. 15 ) . The multivariate linear regression analyses showed that increased bilirubin level ( β = - 0. 009,P = 0. 018 ) ,increased CRP level ( β = -0. 005 ,P <0. 001 ) ,and increased PHQ-9 score ( β = - 0. 008,P = 0. 014) were negatively correlated with the EQ-5D-5L health utility value.Increased 6-MWD ( β = 0. 005,P = 0. 018) was positively correlated with the EQ-5D-5L health utility value.@*Conclusion @# The bilirubin and CRP levels,depression status,and exercise capacity are considered the main factors influencing HRQOL in PD patients.

10.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1021423

RESUMO

BACKGROUND:Inflammation,oxidative stress and bacterial infection are the main causes of delayed wound healing in diabetes.In recent years,various inorganic nanomaterials have been widely used in the treatment of skin wound healing due to their antibacterial activities,but their effects on anti-oxidation and anti-inflammation are limited. OBJECTIVE:To investigate the effect of Prussian blue nanoparticles on the wound repair of diabetes in terms of antioxidant,anti-inflammatory and photothermal antibacterial activities. METHODS:Prussian blue nanoparticles were prepared and characterized.(1)In vitro:The biocompatibility of Prussian blue nanoparticles with different concentrations was detected by MTT assay.The cytoprotective effect of Prussian blue nanoparticles and the intracellular reactive oxidative species level were examined under the condition of hydrogen peroxide.The ability of Prussian blue nanoparticles to decompose hydrogen peroxide and superoxide anion radicals was tested;the effect of Prussian blue nanoparticles on lipopolysaccharide-induced macrophage inflammation was investigated.The photothermal antibacterial activity of Prussian blue nanoparticles was detected by the plate colony counting method.(2)In vivo:ICR mice were intraperitoneally injected with streptozotocin to establish a diabetes mouse model.After the model was successfully established,a 6 mm wound was created on the back with a hole punch.There were the control group(no treatment),the Prussian blue group and the Prussian blue with light group.The wound healing and histomorphological changes were observed. RESULTS AND CONCLUSION:(1)In vitro:Prussian blue nanoparticles in 25-200 μg/mL were non-toxic to cells.Prussian blue nanoparticles had the extremely strong antioxidant capacity and mitigated the intracellular reactive oxidative species at a high oxidative stress environment,resulting in a pronounced cytoprotective effect.The Prussian blue nanoparticles not only exhibited hydrogen peroxide degradation activity but also showed strong superoxide scavenging ability.Prussian blue nanoparticles also displayed significant anti-inflammatory activity and extremely strong antibacterial ability after light irradiation.(2)In vivo:After 14 days,the wound sizes of the Prussian blue group and Prussian blue with light group were significantly reduced,and the healing speed of Prussian blue with light group was the fastest.Hematoxylin-eosin and Masson staining showed a lot of granulation tissue formation and collagen deposition in the Prussian blue group and the Prussian blue with light group,of which the Prussian blue with light group was the most.Immunofluorescence staining displayed that,compared with the control group,the expressions of α-SMA and CD31 were increased significantly in Prussian blue group and Prussian blue with light group(P<0.05),but F4/80 expression was decreased significantly in Prussian blue group and Prussian blue with light group(P<0.05),indicating more obvious improvement in the Prussian blue with light group.(3)These results showed that Prussian blue nanoparticles could promote the skin wound healing of the diabetes mouse model by exerting anti-inflammatory,antioxidant and antibacterial effects.

11.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1039585

RESUMO

Objective @#To explore the correlation between serum fibroblast growth factor⁃23 (FGF23) concentration and heart failure and all⁃cause death in patients with end⁃stage renal disease (ESRD) . @*Methods @#The prospective cohort study design was used in the present study. The ESRD patients who were admitted to the department of nephropathy in the Hospital and without heart failure symptoms were recruited in this study. The data of patients was collected through baseline questionnaires , physical examinations , echocardiography , and laboratory examinations. The serum FGF23 levels were measured by enzyme⁃linked immunosorbent assay (ELISA) . The follow⁃up time was 2 years. The onset of heart failure (ACC/AHA stage C ⁃D) and all⁃cause death were composite endpoint events. The Cox proportional risk model was used to explore the risk factors of outcome events. Through subgroup analyses and interaction analyses , further exploration was conducted to determine whether there was heterogeneity in the association between FGF23 and outcome events in different subgroups.@*Results @#Ultimately , 107 ESRD patients were included in this study , with an average age of (52. 00 ± 12. 51) years. There were 39 males (36. 45% ) , and the median follow⁃up time was 23 months (21 , 25 months) . There were 32 (29. 9% ) outcome events , of which 22 (20. 6% ) onset of heart failure and 10 (9. 3% ) all⁃cause of deaths. The results of this study showed that the concentration of FGF23 in the outcome event group was significantly higher than that in the non⁃event group [(4. 40 ± 1. 16) pmol/ml vs (3. 85 ± 0. 82) pmol/ml ,P < 0. 05] . The Cox proportional risk model showed that the elevated FGF23 was associated with increased risk of the composite endpoint events in ESRD patients (HR = 1. 730 , 95% CI: 1. 164 - 2. 570 , P = 0. 007 ) . Subgroup analyses showed that there was an interactive effect between FGF23 levels and gender on the risk of cardiovascular outcome events. Especially in male ESRD patients , the increased FGF23 level was correlated with a higher risk of cardiovascular events (P⁃interaction < 0. 05) .@*Conclusion @#Elevated serum FGF23 is an independent risk factor for the onset of heart failure and all⁃cause of mortality in ESRD patients , especially in male patients.

12.
Chinese Journal of Biotechnology ; (12): 280-291, 2024.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1008095

RESUMO

In this study, the chloroplast genome of Camellia insularis Orel & Curry was sequenced using high-throughput sequencing technology. The results showed that the chloroplast genome of C. insularis was 156 882 bp in length with a typical tetrad structure, encoding 132 genes, including 88 protein-coding genes, 36 tRNA genes, and 8 rRNA genes. Codon preference analysis revealed that the highest number of codons coded for leucine, with a high A/U preference in the third codon position. Additionally, 67 simple sequence repeats (SSR) loci were identified, with a preference for A and T bases. The inverted repeat (IR) boundary regions of the chloroplast genome of C. insularis were relatively conserved, except for a few variable regions. Phylogenetic analysis indicated that C. insularis was most closely related to C. fascicularis. Yellow camellia is a valuable material for genetic engineering breeding. This study provides fundamental genetic information on chloroplast engineering and offers valuable resources for conducting in-depth research on the evolution, species identification, and genomic breeding of yellow Camellia.


Assuntos
Genoma de Cloroplastos/genética , Filogenia , Melhoramento Vegetal , Camellia/genética , Cloroplastos/genética
13.
Jt Dis Relat Surg ; 35(1): 20-26, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38108162

RESUMO

OBJECTIVES: This study aims to investigate the high-risk factors for osteonecrosis of the femoral head (ONFH) after internal fixation with multiple cannulated compression screws for adult femoral neck fractures and to construct a prediction model. PATIENTS AND METHODS: Between from January 2012 and December 2020, a total of 268 patients (138 males, 130 females; mean age: 53±10 years; range, 23 to 70 years) with ONFH who had complete follow-up data were included. Closed reduction in combination with open reduction were performed. All patients received internal fixation with multiple cannulated compression screws and were assigned to ONFH and non-ONFH groups. Logistic regression model was utilized to identify independent risk factors for postoperative ONFH, followed by constructing a nomogram prediction model. The predictive ability of the model was evaluated by receiver operating characteristic curve, Hosmer-Lemeshow test, and calibration curve. RESULTS: Multivariate analysis revealed that older age (odds ratio [OR]: 2.307, 95% confidence interval [CI]: 1.295-4.108], Charlson Comorbidity Index (CCI) ≥2 (OR: 2.214, 95% CI: 1.035-4.739), fracture displacement (OR: 2.426, 95% CI: 1.122-5.247), unsatisfactory reduction (OR: 2.629, 95% CI: 1.275-5.423), postoperative removal of internal fixation implant (OR: 2.200, 95% CI: 1.051-4.604) were independent risk factors for postoperative ONFH (p<0.05). The nomogram prediction model constructed based on these clinical characteristics showed high predictive value (AUC=0.807) and consistency (p>0.05). CONCLUSION: Age, comorbidity index, fracture type, reduction quality and postoperative removal of internal fixation implant are of utmost importance for postoperative ONFH in patients with femoral neck fractures. The established nomogram prediction model can accurately predict the occurrence of postoperative ONFH.


Assuntos
Fraturas do Colo Femoral , Osteonecrose , Masculino , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Cabeça do Fêmur , Osteonecrose/etiologia , Osteonecrose/cirurgia , Fatores de Risco , Fraturas do Colo Femoral/cirurgia , Fixação Interna de Fraturas/efeitos adversos
14.
Eur J Pharmacol ; 966: 176270, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38096970

RESUMO

AIM: Liver fibrosis remains a great challenge in the world. Spinosin (SPI), a natural flavonoid-C-glycoside, possesses various pharmacological activities including anti-inflammatory and anti-myocardial fibrosis effects. In this study, we investigate whether SPI can be a potential lead for the treatment of liver fibrosis and explore whether the orphan nuclear receptor Nur77, a negative regulator of liver fibrosis development, plays a critical role in SPI's action. METHODS: A dual luciferase reporter system of α-SMA was established to evaluate the effect of SPI on hepatic stellate cell (HSC) activation in LX2 and HSC-T6 cells. A mouse model of CCl4-induced liver fibrosis was used to test the efficacy of SPI against liver fibrosis. The expression levels of Nur77, inflammatory cytokines and collagen were determined by Western blotting and qPCR. Potential kinase pathways involved were also analyzed. The affinity of Nur77 with SPI was documented by fluorescence titration. RESULTS: SPI can strongly suppress TGF-ß1-mediated activation of both LX2 and HSC-T6 cells in a dose-dependent manner. SPI increases the expression of Nur77 and reduces TGF-ß1-mediated phosphorylation levels of ASK1 and p38 MAPK, which can be reversed by knocking out of Nur77. SPI strongly inhibits collagen deposition (COLA1) and reduces inflammatory cytokines (IL-6 and IL-1ß), which is followed by improved liver function in the CCl4-induced mouse model. SPI can directly bind to R515 and R563 in the Nur77-LBD pocket with a Kd of 2.14 µM. CONCLUSION: Spinosin is the major pharmacological active component of Ziziphus jujuba Mill. var. spinosa which has been frequently prescribed in traditional Chinese medicine. We demonstrate here for the first time that spinosin is a new therapeutic lead for treatment of liver fibrosis by targeting Nur77 and blocking the ASK1/p38 MAPK signaling pathway.


Assuntos
Células Estreladas do Fígado , Fator de Crescimento Transformador beta1 , Camundongos , Animais , Fator de Crescimento Transformador beta1/metabolismo , Transdução de Sinais , Linhagem Celular , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/metabolismo , Flavonoides/farmacologia , Citocinas/metabolismo , Modelos Animais de Doenças , Colágeno/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Fígado
15.
Medicine (Baltimore) ; 102(50): e36234, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38115296

RESUMO

RATIONALE: Patients who have myasthenia gravis or dermatomyositis show clinical signs of muscular weakening. Ocular muscle involvement is uncommon, and symmetrical proximal limb weakness is the typical presentation of dermatomyositis. However, the earliest and most noticeable sign in those with myasthenia gravis is extraocular muscular paralysis. Dermatomyositis is frequently complicated by malignancy, and the common malignancies associated with dermatomyositis vary by region and ethnicity, while thymoma is relatively rare. About 10% to 15% of people with myasthenia gravis have thymoma, which is involved in the etiology of the disease. PATIENT CONCERNS: A 68-year-old female presented with ocular muscle weakness for 10 days that manifested as bilateral blepharoptosis with the phenomenon of "light in the morning and heavy in the evening." Imaging examination showed anterior mediastinal thymic tumor with metastasis. DIAGNOSES: After a thorough physical examination, we discovered bilateral upper limbs with grade IV muscle strength and the typical rash of dermatomyositis. In combination with elevated serum kinase levels and electromyography suggesting myogenic damage, the patient was finally diagnosed as dermatomyositis with multiple metastases of thymoma. INTERVENTIONS: The patient received oral hydroxychloroquine sulfate, topical corticosteroids, and tacrolimus ointment, but these did not work very well. Subsequently, the patient underwent surgery combined with radiotherapy for the thymoma. OUTCOMES: Muscle weakness in the patient improved after effective treatment of tumor, and the rash mostly disappeared. CONCLUSION: Ocular muscle weakness and thymoma are more common in myasthenia gravis, but we cannot ignore the possibility of dermatomyositis. To further establish the diagnosis, a thorough physical examination and laboratory findings are required. Further tumor screening should be performed for patients with dermatomyositis. Early detection and management of possible tumors are essential to the treatment of dermatomyositis linked to malignancies.


Assuntos
Dermatomiosite , Exantema , Miastenia Gravis , Timoma , Neoplasias do Timo , Feminino , Humanos , Idoso , Timoma/complicações , Timoma/diagnóstico , Timoma/cirurgia , Dermatomiosite/diagnóstico , Dermatomiosite/complicações , Miastenia Gravis/tratamento farmacológico , Neoplasias do Timo/complicações , Neoplasias do Timo/diagnóstico , Neoplasias do Timo/cirurgia , Debilidade Muscular , Exantema/complicações
16.
RSC Adv ; 13(46): 32104-32109, 2023 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-37920764

RESUMO

The geochemistry of Li and Li isotopes is a promising tracer of chemical weathering processes for both modern and ancient times. Therefore, accurate and precise determination of the isotopic composition of Li is required for a large variety of complex geological samples with different Li concentrations and matrix/Li ratios. Especially, geochemical studies of precious geological samples with ultra-low lithium content and high matrix. In this study, the accuracy and the precision corresponding to Li isotopic measurements of low-level samples using multi-collector inductively coupled plasma mass spectrometry (MC-ICP-MS) with membrane desolvation introduction system was evaluated. The method of MC-ICP-MS with membrane desolvation and a high-sensitivity X-skimmer cone, together with a simple one-step column separation enabled the high-precision isotopic analysis of Li quantities as small as 2 ng. The long-term instrumental external reproducibility of δ7Li values for the L-SVEC and SPEX-Li were 0.0 ± 0.1‰ (n = 20) and 12.1 ± 0.4‰ (n = 20), respectively. Based on the measurements on a series of international reference materials over the last two years. The measured δ7Li values for the standards with a variety of matrices, including BHVO-2, AGV-2 and seawater (NASS-6). The δ7Li values of BHVO-2 (4.58 ± 0.35‰), AGV-2 (6.85 ± 0.40‰) and NASS-6 (30.88 ± 0.20‰) are in agreement with the published data within the uncertainty. We also present analytical results for South China Sea surface seawater water, meteorite, limestones and rain water. These results demonstrate the validity of the method for obtaining highly precise and accurate outcomes.

17.
Bioorg Chem ; 140: 106795, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37657195

RESUMO

Hepatic fibrosis remains a great challenge clinically. The orphan nuclear receptor Nur77 is recently suggested as the critical regulator of transforming growth factor-ß (TGF-ß) signaling, which plays a central role in multi-organic fibrosis. Herein, we optimized our previously reported Nur77-targeted compound 9 h for attempting to develop effective and safe anti-hepatic fibrosis agents. The critical pharmacophore scaffold of pyridine-carbonyl-hydrazine-1-carboxamide was retained, while the naphthalene ring was replaced with an aromatic ring containing pyridyl or indole groups. Four series of derivatives were thus generated, among which the compound 16f had excellent binding activity toward Nur77-LBD (KD = 470 nM) with the best inhibitory activity against the TGF- ß 1 activation of hepatic stellate cells (HSCs) and low cytotoxicity to normal mice liver AML-12 cells (IC50 > 80 µM). In mice, 16f displayed potent activity against CCl4-induced liver fibrosis with improved liver function. Mechanistically, 16f-mediated inactivation of HSC and suppression of liver fibrosis were associated with its enhancement of autophagic flux in a Nur77-dependent manner. Together, 16f was identified as a potential anti-liver fibrosis agent. Our study suggests that Nur77 may serve as a critical anti-hepatic fibrosis target.


Assuntos
Anticonvulsivantes , Cirrose Hepática , Animais , Camundongos , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/tratamento farmacológico , Antifibróticos , Autofagia , Células Estreladas do Fígado
18.
J Exp Anal Behav ; 2023 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-37203271

RESUMO

A cross-cultural comparison is made of delay discounting in samples of participants from Chile and China. Comparisons are made based on previous literature that suggests that individuals from an Asian culture should be willing to postpone delayed rewards more than are individuals from a Latin American culture. To test the cross-cultural validity of a hyperbolic discounting model, the model was fitted to both data sets. Additionally, a self-enhancement measure was evaluated as a potential mediator between culture of origin and delay discounting. Seventy-eight college students from China and 120 college students from Chile, with similar demographic backgrounds, discounted hypothetical monetary outcomes using an adjusting-amount titration procedure. Additionally, participants completed a self-enhancement measure. Age, academic major, gender, and grade point average were controlled. Chilean participants discounted much more steeply than Chinese nationals did. No support was obtained for the mediation of self-enhancement between culture of origin and degree of delay discounting. In both samples, delay discounting was better described by a hyperboloid than an exponential function, the only exception being the $10,000 condition in which the medians for Chilean participants' present subjective value were equally well explained by a hyperboloid and an exponential function.

19.
RSC Adv ; 13(19): 12792-12798, 2023 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-37114022

RESUMO

Lithium-sulfur batteries (LSBs) are some of the most promising energy storage systems to break the ceiling of Li-ion batteries. However, the notorious shuttle effect and slow redox kinetics give rise to low sulfur utilization and discharge capacity, poor rate performance, and fast capacity decay. It is proved that the reasonable design of the electrocatalyst is one of the important ways to improve the electrochemical performance of LSBs. Here, a core-shell structure with gradient adsorption capacity for reactants and sulfur products was designed. The Ni nanoparticles core coated with graphite carbon shell was prepared by one-step pyrolysis of Ni-MOF precursors. The design takes advantage of the principle that the adsorption capacity decreases from the core to the shell, and the Ni core with strong adsorption capacity is easy to attract and capture soluble lithium polysulfide (LiPS) during the discharge/charging process. This trapping mechanism prevents the diffusion of LiPSs to the outer shell and effectively inhibits the shuttle effect. In addition, the Ni nanoparticles within the porous carbon, as the active center, expose most of the inherent active sites to the surface area, thus achieving a rapid transformation of LiPSs, significantly reducing the reaction polarization, and improving the cyclic stability and reaction kinetics of LSB. Therefore, the S/Ni@PC composites exhibited excellent cycle stability (a capacity of 417.4 mA h g-1 for 500 cycles at 1C with a fading rate of 0.11%) and outstanding rate performance (1014.6 mA h g-1 at 2C). This study provides a promising design solution of Ni nanoparticles embedded in porous carbon for high-performance, safe and reliable LSB.

20.
Sensors (Basel) ; 23(4)2023 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-36850713

RESUMO

The Taiyuan Xishan Ecological Restoration Zone is located in the west of Taiyuan City and belongs to the Xishan Coalfield. Due to the resource development activity of coal mining, which is caused by coal gangue accumulation, surface vegetation degradation, bare surfaces, and other phenomena, it is most common in this area. These have an impact on the surface ecology; however, after ecological restoration, the surface ecology has been greatly improved. There are many extraction models of vegetation coverage based on pixel dichotomology combined with multispectral vegetation index, but we believe that the combination of visible light vegetation index to construct models is relatively unexplored. The main problem of how to use the RGB image data in order to quickly and accurately extract vegetation coverage information is still under investigation and needs researchers' attention. In this paper, through selecting the vegetation coverage as the evaluation index of ecological restoration effect, a new RGB vegetation coverage CIVE calculation model is innovatively proposed to solve the above problem, and on the basis of this model, the vegetation cover change analysis is carried out in the Xishan ecological restoration area of Taiyuan. According to the analysis of vegetation coverage change, relevant paper data, and the characteristics of multiple historical remote sensing images, the ecological restoration area of Taiyuan Xishan is divided into six typical areas. Through empirical evaluation, we summarize and analyze these six typical areas, which can provide typical demonstration roles for other ecological restoration areas. Our findings suggest that the proposed CIVE model realizes the extraction of vegetation cover information and long-term series dynamic monitoring of vegetation coverage.

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