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1.
Am J Transl Res ; 16(8): 3742-3750, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39262724

RESUMO

OBJECTIVE: To observe the therapeutic effect of Sacubitril Valsartan sodium tablets (SVST) on heart failure (HF) complicated by pulmonary infection (PI), and to provide a reference for future medication. METHODS: A total of 89 patients with HF complicated by PI who were treated at Dongying People's Hospital from January 2019 to May 2020 were selected as study subjects in this retrospective study. The control group consisted of 41 patients who received conventional treatment, while the study group included 48 patients who received SVST in addition to conventional treatment. The time to disappearance/improvement of chest tightness, shortness of breath, cough, and moist rales in both groups were recorded. The levels of brain natriuretic peptide (BNP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and procalcitonin (PCT) were measured before and after treatment. Changes in cardiac function were observed, and the Clinical Pulmonary Infection Score (CPIS) and Sequential Organ Failure Assessment (SOFA) were used to assess PI. The clinical efficacy and adverse reactions were evaluated after treatment. Follow-up lasted 2 years, during which the readmission rate due to HF and mortality rate were calculated. RESULTS: Patients in the study group experienced a shorter time to disappearance/improvement of chest tightness, shortness of breath, cough, and moist rales compared to the control group (all P<0.05). The study group also showed reduced levels of BNP, IL-6, TNF-α, and PCT, as well as lower CPIS and SOFA scores after treatment (all P<0.05), with significantly improved cardiac function (P<0.05). Additionally, the total effective rate was higher in the study group than in the control group (P<0.05), and there was no significant difference in adverse reactions between the two groups (P>0.05). Follow-up revealed no difference in mortality between the two groups (P>0.05), but the study group had a lower readmission rate (P<0.05). CONCLUSION: SVST is effective in treating HF complicated by PI, ensures a good prognosis for patients, and is recommended for clinical use.

2.
Cell Mol Biol Lett ; 29(1): 123, 2024 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-39277732

RESUMO

BACKGROUND: Loss-of-function mutations of ZBTB24 cause immunodeficiency, centromeric instability, and facial anomalies syndrome 2 (ICF2). ICF2 is a rare autosomal recessive disorder with immunological defects in serum antibodies and circulating memory B cells, resulting in recurrent and sometimes fatal respiratory and gastrointestinal infections. The genotype-phenotype correlation in patients with ICF2 indicates an essential role of ZBTB24 in the terminal differentiation of B cells. METHODS: We used the clustered regularly interspaced short palindromic repeats (CRISPER)/Cas9 technology to generate B cell specific Zbtb24-deficient mice and verified the deletion specificity and efficiency by quantitative polymerase chain reaction (Q-PCR) and western blotting analyses in fluorescence-activated cell sorting (FACS)-sorted cells. The development, phenotype of B cells and in vivo responses to T cell dependent or independent antigens post immunization were analyzed by flow cytometry and enzyme-linked immunosorbent assay (ELISA). Adoptive transfer experiment in combination with in vitro cultures of FACS-purified B cells and RNA-Seq analysis were utilized to specifically determine the impact of Zbtb24 on B cell biology as well as the underlying mechanisms. RESULTS: Zbtb24 is dispensable for B cell development and maintenance in naive mice. Surprisingly, B cell specific deletion of Zbtb24 does not evidently compromise germinal center reactions and the resulting primary and secondary antibody responses induced by T cell dependent antigens (TD-Ags), but significantly inhibits T cell independent antigen-elicited antibody productions in vivo. At the cellular level, Zbtb24-deficiency specifically impedes the plasma cell differentiation of B1 cells without impairing their survival, activation and proliferation in vitro. Mechanistically, Zbtb24-ablation attenuates heme biosynthesis partially through mTORC1 in B1 cells, and addition of exogenous hemin abrogates the differentiation defects of Zbtb24-null B1 cells. CONCLUSIONS: Zbtb24 seems to regulate antibody responses against TD-Ags B cell extrinsically, but it specifically promotes the plasma cell differentiation of B1 cells via heme synthesis in mice. Our study also suggests that defected B1 functions contribute to recurrent infections in patients with ICF2.


Assuntos
Diferenciação Celular , Doenças da Imunodeficiência Primária , Fatores de Transcrição , Animais , Camundongos , Linfócitos B/imunologia , Linfócitos B/metabolismo , Face/anormalidades , Síndromes de Imunodeficiência/genética , Camundongos Endogâmicos C57BL , Camundongos Knockout , Doenças da Imunodeficiência Primária/genética , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Fatores de Transcrição/metabolismo
3.
BMC Microbiol ; 24(1): 288, 2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-39095694

RESUMO

BACKGROUND: Coral diseases are significant drivers of global coral reef degradation, with pathogens dominated by Vibrio coralliilyticus playing a prominent role in the development of coral diseases. Coral phenotype, symbiotic microbial communities, and host transcriptional regulation have been well-established as factors involved in determining coral disease resistance, but the underlying mechanisms remain incompletely understood. METHODS: This study employs high-throughput sequencing to analyse the symbiotic microbial and transcriptional response of the hosts in order to evaluate the disease resistance of Acropora valida and Turbinaria peltata exposed to Vibrio coralliilyticus. RESULTS: A. valida exhibited pronounced bleaching and tissue loss within 7 h of pathogen infection, whereas T. peltata showed no signs of disease throughout the experiment. Microbial diversity analyses revealed that T. peltata had a more flexible microbial community and a higher relative abundance of potential beneficial bacteria compared to A. valida. Although Vibrio inoculation resulted in a more significant decrease in the Symbiodiniaceae density of A. valida compared to that of T. peltata, it did not lead to recombination of the coral host and Symbiodiniaceae in either coral species. RNA-seq analysis revealed that the interspecific differences in the transcriptional regulation of hosts after Vibrio inoculation. Differentially expressed genes in A. valida were mainly enriched in the pathways associated with energy supply and immune response, such as G protein-coupled receptor signaling, toll-like receptor signaling, regulation of TOR signaling, while these genes in T. peltata were mainly involved in the pathway related to immune homeostasis and ion transport, such as JAK-STAT signaling pathway and regulation of ion transport. CONCLUSIONS: Pathogenic challenges elicit different microbial and transcriptional shifts across coral species. This study offers novel insights into molecular mechanisms of coral resistance to disease.


Assuntos
Antozoários , Resistência à Doença , Vibrio , Antozoários/microbiologia , Antozoários/genética , Antozoários/imunologia , Animais , Vibrio/genética , Resistência à Doença/genética , Simbiose/genética , Microbiota/genética , Recifes de Corais , Sequenciamento de Nucleotídeos em Larga Escala
4.
Zool Res ; 45(5): 990-1000, 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39147714

RESUMO

The von Hippel-Lindau tumor suppressor protein (VHL), an E3 ubiquitin ligase, functions as a critical regulator of the oxygen-sensing pathway for targeting hypoxia-inducible factors. Recent evidence suggests that mammalian VHL may also be critical to the NF-κB signaling pathway, although the specific molecular mechanisms remain unclear. Herein, the roles of mandarin fish ( Siniperca chuatsi) VHL ( scVHL) in the NF-κB signaling pathway and mandarin fish ranavirus (MRV) replication were explored. The transcription of scVHL was induced by immune stimulation and MRV infection, indicating a potential role in innate immunity. Dual-luciferase reporter gene assays and reverse transcription quantitative PCR (RT-qPCR) results demonstrated that scVHL evoked and positively regulated the NF-κB signaling pathway. Treatment with NF-κB signaling pathway inhibitors indicated that the role of scVHL may be mediated through scIKKα, scIKKß, scIκBα, or scp65. Co-immunoprecipitation (Co-IP) analysis identified scIκBα as a novel target protein of scVHL. Moreover, scVHL targeted scIκBα to catalyze the formation of K63-linked polyubiquitin chains to activate the NF-κB signaling pathway. Following MRV infection, NF-κB signaling remained activated, which, in turn, promoted MRV replication. These findings suggest that scVHL not only positively regulates NF-κB but also significantly enhances MRV replication. This study reveals a novel function of scVHL in NF-κB signaling and viral infection in fish.


Assuntos
Doenças dos Peixes , NF-kappa B , Ranavirus , Transdução de Sinais , Replicação Viral , Animais , NF-kappa B/metabolismo , NF-kappa B/genética , Replicação Viral/fisiologia , Doenças dos Peixes/virologia , Ranavirus/fisiologia , Proteína Supressora de Tumor Von Hippel-Lindau/metabolismo , Proteína Supressora de Tumor Von Hippel-Lindau/genética , Infecções por Vírus de DNA/veterinária , Infecções por Vírus de DNA/virologia , Proteínas de Peixes/metabolismo , Proteínas de Peixes/genética , Proteínas I-kappa B/metabolismo , Proteínas I-kappa B/genética , Regulação da Expressão Gênica
5.
Heliyon ; 10(15): e34602, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39157321

RESUMO

Background: Peripheral artery disease (PAD) represents the frequently seen circulatory condition related to a risk of critical limb ischemia and amputation. Critical lower extremity ischemia may require amputation, and the outcomes vary. In this study, we developed an artificial intelligence (AI)-driven predictive model for PAD subtypes to assess risk among patients more precisely and accurately to predict disease progression. Methods: The present retrospective study examined clinical data in PAD patents undergoing lower extremity amputation. The data were analyzed using an unsupervised machine learning algorithm (UMLA) for subgroup identification and risk stratification. The clustering result accuracy was validated by analyzing the follow-up data of clusters. Finally, we built the prediction model with binary logistic regression. Results: In total, we enrolled 507 cases into this work. Two distinct subgroups, consisting of Clusters 1 and 2, were identified by UMLA; those from Cluster 1 showed markedly poorer conditions and prognostic outcomes compared with those from Cluster 2. With regard to the new PAD subtype, we established a nomogram with eight predictive factors, including gender, age, smoking history, diabetes and coronary heart disease history, albumin levels, endovascular intervention, and amputation level. The nomogram could accurately categorize patients into two identified clusters, and the area under receiver operating characteristic curve was 0.861 (95 % confidence interval: 0.830-0.893). Conclusion: In this study, UMLA was used to identify new phenotypic subgroups among PAD cases who showed different risks of amputation. Our constructed AI-driven predictive model for PAD subtypes showed that it can be used for risk stratification and clinical management with high accuracy and reliability.

8.
Front Psychol ; 15: 1400094, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39114588

RESUMO

Introduction: Sport anxiety not only impacts the performance of college athletes but also influences their psychological well-being. The psychological well-being of sports students is crucial for both academic performance and competition, as they need to balance their academic performance with professional athletic training. Method: Based on self-determination theory, this study examines the relationship between various factors in sport anxiety (somatic anxiety, worry, and concentration disruption) and subjective happiness, as well as the mediating role of need satisfaction in this relationship. A total of 835 college athletic students participated in the study, completing the Sport Anxiety Scale-2, Basic Psychological Needs Satisfaction Scale-in General, and Subjective Happiness Scale. Results: An analysis of gender differences revealed that female participants scored significantly higher on somatic anxiety (t = -2.21, df = 833, p = 0.028, Cohen's d = -0.155) and worry (t = -3.17, df = 833, p = 0.002, Cohen's d = -0.223) compared to males. In the analysis by sport type, participants engaged in team sports scored significantly higher on somatic anxiety (t = 2.70, df = 833, p = 0.007, Cohen's d = 0.187), Worry (t = 1.97, df = 833, p = 0.049, Cohen's d = 0.136), and concentration disruption (t = 2.73, df = 833, p = 0.007, Cohen's d = 0.189) than those in individual sports. Additionally, in the analysis by grade level, freshman college athletes exhibited significantly lower sport anxiety compared to sophomore athletes [F(4, 830) = 4.06, p = 0.003, η p 2 =0.019]. The mediation analysis revealed that concentration disruption in sport anxiety is significantly and negatively related to subjective happiness. Additionally, need satisfaction (competence, autonomy, and relatedness) mediates the relationship between worry, as well as concentration disruption in sport anxiety and subjective happiness. Discussion: Future research should build on the current study by employing longitudinal designs and integrating multiple objective measures to further explore the relationship between sport anxiety and subjective happiness.

9.
10.
Asian J Surg ; 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-39168734

RESUMO

To retrieve, analyze, and extract evidence related to subcutaneous emphysema in patients undergoing laparoscopic surgery systematically, and provide evidence-based recommendations for reducing its incidence. By browsing the websites of the National Institute for Health and Clinical Excellence, the International Guideline Collaboration Network, the National Guideline Library of the United States, the Registered Nurses Association of Ontario, the Scottish Intercollegiate Guideline Network, the Clinical Practice Guidelines website of the Canadian Medical Association, UpToDate, Web of Science, PubMed, OVID, Cochrane Library, Embase, Chinese Biomedical Database, CNKI, VIP, and Wanfang Database, relevant literatures, guidelines, systematic reviews, evidence summaries, expert consensus, randomized controlled trials, etc. about subcutaneous emphysema in patients undergoing laparoscopic surgery were retrieved. All searches were limited to articles published between 1st January 2010 to 1st August 2023. 2245 articles were identified in total, 10 articles were included after exclude literature that does not meet the standards, including 3 clinical decision-making articles, 2 review papers, and 5 randomized controlled trials. Evidence summarization was conducted from 5 aspects: influencing factors, prevention, establishment and management of pneumoperitoneum, intraoperative monitoring, and intervention methods, 15 pieces of best evidences were summarized. Clinical staffs should transform and apply the evidence-based practices to decrease the incidence of subcutaneous emphysema and enhance the quality of life for patients.

11.
Comput Methods Programs Biomed ; 256: 108384, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39205335

RESUMO

BACKGROUND AND OBJECTIVE: Medicine image classification are important methods of traditional medical image analysis, but the trainable data in medical image classification is highly imbalanced and the accuracy of medical image classification models is low. In view of the above two common problems in medical image classification. This study aims to: (i) effectively solve the problem of poor training effect caused by the imbalance of class imbalanced data sets. (ii) propose a network framework suitable for improving medical image classification results, which needs to be superior to existing methods. METHODS: In this paper, we put in the diffusion model multi-scale feature fusion network (DMSFF), which mainly uses the diffusion generation model to overcome imbalanced classes (DMOIC) on highly imbalanced medical image datasets. At the same time, it is processed according to the cropped image augmentation strategy through cropping (IASTC). Based on this, we use the new dataset to design a multi-scale feature fusion network (MSFF) that can fully utilize multiple hierarchical features. The DMSFF network can effectively solve the problems of small and imbalanced samples and low accuracy in medical image classification. RESULTS: We evaluated the performance of the DMSFF network on highly imbalanced medical image classification datasets APTOS2019 and ISIC2018. Compared with other classification models, our proposed DMSFF network achieved significant improvements in classification accuracy and F1 score on two datasets, reaching 0.872, 0.731, and 0.906, 0.836, respectively. CONCLUSIONS: Our newly proposed DMSFF architecture outperforms existing methods on two datasets, and verifies the effectiveness of generative model inverse balance for imbalance class datasets and feature enhancement by multi-scale feature fusion. Further, the method can be applied to other class imbalanced data sets where the results will be improved.


Assuntos
Processamento de Imagem Assistida por Computador , Humanos , Processamento de Imagem Assistida por Computador/métodos , Algoritmos , Redes Neurais de Computação , Diagnóstico por Imagem/métodos , Bases de Dados Factuais , Interpretação de Imagem Assistida por Computador/métodos
12.
Nat Commun ; 15(1): 7273, 2024 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-39179619

RESUMO

Metal-organic frameworks (MOFs), recognized as advanced catalyst carriers due to their adjustable porous, diverse structure and highly exposed active sites, have earned increasing attention for their potential to address the longevity of catalytic centers. In this manuscript, we have devised and synthesized a multifunctional amino-pyridine benzoic acid (APBA) ligand to replace the modulator ligand of the MOF-808 and disperse the palladium catalytic centers atomically on the MOF-APBA. The resulting single-site catalytic system, Pd@MOF-APBA, demonstrates preeminent efficiency and stability, as evidenced by a high average turnover number (95000) and a low metal residue (4.8 ppm) in the Heck reaction. This catalyst has exhibited recyclability for multiple runs without significant loss of reactivity for gram-scale reactions. The catalyst's high activity and efficiency can be attributed to the suitable electrical properties and structures of the N, N'-bidentate ligand for the catalytic palladium ions, postponing their deactivations, including leaching and agglomeration.

13.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 32(4): 1129-1135, 2024 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-39192409

RESUMO

OBJECTIVE: To investigate the correlation of peripheral blood T lymphocyte subsets with overall survival (OS) and clinical baseline characteristics in mantle cell lymphoma (MCL). METHODS: The clinical data of 55 MCL patients who were newly diagnosed in the Department of Hematology, Second Hospital of Shanxi Medical University from January 2012 to July 2022 were analyzed retrospectively. The percentages of T lymphocyte subsets and CD4+/CD8+ ratio in peripheral blood were detected by flow cytometry, and their correlation with clinical characteristics of patients were analyzed. Kaplan-Meier method was used for survival analysis and survival curves were drawn. Log-rank test was used for univariate analysis, while Cox proportional hazards model was used for multivariate analysis. RESULTS: The median follow-up was 40(1-68) months, and the median overall survival (OS) was 47 months. Among the 55 patients, 30(54.5%) patients had a decrease in peripheral blood CD4+T lymphocyte, while 17(30.9%) patients had a increase in peripheral blood CD8+T lymphocyte, and 20(36.4%) patients had a decrease in CD4+/CD8+ ratio. There were no significant correlations between CD4+/CD8+ ratio and sex, age, Ki-67, B symptoms, leukocytes, hemoglobin, lymphocytes, platelets, albumin, lactate dehydrogenase (LDH), ß2-microglobulin, splenomegaly, bone marrow invasion, primary site and MIPI score. Survival analysis showed that patients with CD4+T cell >23.3%, CD8+T cell ≤33.4% and CD4+/CD8+ ratio >0.6 had longer OS (P =0.020, P <0.001, P <0.001). Univariate analysis showed that Ki-67>30%, LDH>250 U/L, splenomegaly, bone marrow involvement, CD4+T cells ≤23.3%, CD8+ T cells >33.4%, CD4+/CD8+ ratio ≤0.6 were adverse prognostic factors affecting OS of MCL patients. Multivariate analysis showed that CD4+/CD8+ ratio ≤0.6 (HR =4.382, P =0.005) was an independent adverse prognostic factor for OS of MCL patients. CONCLUSIONS: Low CD4+/CD8+ ratio is associated with poor prognosis in MCL, and the CD4+/CD8+ ratio can be used as an important indicator to evaluate the prognosis risk in MCL patients.


Assuntos
Relação CD4-CD8 , Linfoma de Célula do Manto , Humanos , Linfoma de Célula do Manto/sangue , Prognóstico , Estudos Retrospectivos , Linfócitos T CD8-Positivos , Modelos de Riscos Proporcionais , Masculino , Feminino , Subpopulações de Linfócitos T , Pessoa de Meia-Idade
14.
BMC Pharmacol Toxicol ; 25(1): 54, 2024 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-39169392

RESUMO

BACKGROUND: Non-small cell lung cancer (NSCLC) is associated with intracellular copper accumulation. Antioxidant 1 (ATOX1) is a copper chaperone. This study aimed to analyze the anti-cancer effects of curcumin on the ATOX1-mediated copper pathway in NSCLC. METHODS: A binding activity between curcumin and ATOX1 was measured using molecular docking. NSCLC cells, A549 and H1299, were treated with different doses of curcumin (10, 20, 40 µM) or DC-AC50 (5, 10, 20 µM) for 24 h. The cell viability and levels of ATOX1, ATP7A and COX17 proteins were observed in cells. Overexpressing ATOX1 in cells was established by pcDNA3.1-ATOX1 transfection for 24 h. The ATOX1 overexpressing cells were treated with 40 µM curcumin or 20 µM DC-AC50 for 24 h to analyze the mechanism of curcumin in NSCLC treatment. Cell viability was measured by CCK-8, and levels of proteins were measured by western blotting. The copper level in cells was labeled by copper sensor-1. Moreover, nude mice models were induced by injection of A549 cells and treated with 20 mg/kg/d DC-AC50 or 40 mg/kg/d curcumin. Tumor growth was observed by measuring tumor volume and tumor weight. The levels of ATOX1, ATP7A and COX17 in tumors were measured by immunohistochemistry and western blotting. RESULTS: Curcumin bound to ATOX1 (score = -6.1 kcal/mol) and decreased the levels of ATOX1, ATP7A and COX17 proteins in NSCLC cells. The curcumin or DC-AC50 treatment suppressed cell viability by inhibiting the ATOX1-mediated copper signaling in NSCLC cells. The ATOX1 overexpression in cells significantly weakened the effects of curcumin on suppressing copper accumulation and the ATOX1-mediated copper pathway (p < 0.05). In mice models, curcumin or DC-AC50 treatment also suppressed tumor growth by suppressing the ATOX1-mediated copper pathway in tumors. CONCLUSION: This study demonstrated that curcumin bound ATOX1 to suppress copper accumulation in NSCLC cells, providing a new mechanism of curcumin for NSCLC treatment.


Assuntos
Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Proteínas de Transporte de Cobre , Cobre , Curcumina , Neoplasias Pulmonares , Animais , Humanos , Camundongos , Células A549 , Antineoplásicos/farmacologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cobre/metabolismo , Proteínas de Transporte de Cobre/metabolismo , Curcumina/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Metalochaperonas/metabolismo , Camundongos Endogâmicos BALB C , Camundongos Nus , Chaperonas Moleculares/metabolismo , Simulação de Acoplamento Molecular , Ensaios Antitumorais Modelo de Xenoenxerto
15.
Int J Biol Macromol ; 277(Pt 1): 134008, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39032879

RESUMO

In this study, an active film composed of gallic acid (GA), chitosan (CS), and cellulose nanocrystals (CNC) was prepared using a solution casting method and synergistic photodynamic inactivation (PDI) technology. Characterization of the film showed that the CS-CNC-GA composite film had high transparency and UV-blocking ability. The addition of GA (0.2 %-1.0 %) significantly enhanced the mechanical properties, water resistance, and thermal stability of the film. The tensile strength increased up to 46.30 MPa, and the lowest water vapor permeability was 1.16 × e-12 g/(cm·s·Pa). The PDI-treated CS-CNC-GA1.0 composite film exhibited significantly enhanced antibacterial activity, with inhibition zone diameters of 31.83 mm against Staphylococcus aureus and 21.82 mm against Escherichia coli. The CS-CNC-GA composite film also showed good antioxidant activity. Additionally, the CS-CNC-GA1.0 composite film generated a large amount of singlet oxygen under UV-C light irradiation. It was found that using the CS-CNC-GA1.0 composite film for packaging and storage of oysters at 4 °C effectively delayed the increase in pH, total colony count, and lipid oxidation in oysters. In conclusion, the CS-CNC-GA composite film based on PDI technology has great potential for applications in the preservation of aquatic products.


Assuntos
Antibacterianos , Celulose , Quitosana , Ácido Gálico , Ácido Gálico/química , Ácido Gálico/farmacologia , Quitosana/química , Celulose/química , Antibacterianos/farmacologia , Antibacterianos/química , Antioxidantes/química , Antioxidantes/farmacologia , Escherichia coli/efeitos dos fármacos , Embalagem de Alimentos/métodos , Staphylococcus aureus/efeitos dos fármacos , Nanopartículas/química , Permeabilidade , Nanocompostos/química , Resistência à Tração , Raios Ultravioleta
16.
Acta Pharmacol Sin ; 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-39043968

RESUMO

Small cell lung cancer (SCLC) is a recalcitrant malignancy with dismal prognosis due to rapid relapse after an initial treatment response. More effective treatments for SCLC are desperately needed. Our previous studies showed that cell migration-inducing hyaluronan binding protein (CEMIP) functionally promotes SCLC cell proliferation and metastasis. In this study, we investigated whether and how CEMIP regulates the chemosensitivity of SCLC. Through the GDSC database, we found that CEMIP expression levels were positively correlated with the IC50 values of several commonly used chemotherapeutic drugs in SCLC cells (cisplatin, gemcitabine, 5-fluorouracil and cyclophosphamide). We demonstrated that overexpression or knockdown of CEMIP in SCLC cells resulted in a notable increase or reduction in the IC50 value of cisplatin or etoposide, respectively. We further revealed that CEMIP functions as an adaptor protein in SCLC cells to interact with SRC and YAP through the 1-177 aa domain and 820-1361 aa domain, respectively, allowing the autophosphorylation of Y416 and activation of SRC, thus facilitating the interaction between YAP and activated SRC, and resulting in increased phosphorylation of Y357, protein stability, nuclear accumulation and transcriptional activation of YAP. Overexpressing SRC or YAP counteracted the CEMIP knockdown-mediated increase in the sensitivity of SCLC cells to cisplatin and etoposide. The combination of the SRC inhibitor dasatinib or the YAP inhibitor verteporfin and cisplatin/etoposide (EP regimen) displayed excellent synergistic antitumor effects on SCLC both in vitro and in vivo. This study demonstrated that targeted therapy against the CEMIP/SRC/YAP complex is a potential strategy for SCLC and provides a rationale for the development of future clinical trials with translational prospects.

17.
Discov Oncol ; 15(1): 317, 2024 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-39073546

RESUMO

BACKGROUND: Colorectal cancer (CRC) is a prevalent malignancy with high morbidity and mortality rates. Previous studies have demonstrated that interleukin (IL)-22 is involved in CRC progression; however, the exact mechanism remains unclear. This study aimed to investigate the effects of IL-22 on CRC cell proliferation and metastasis. METHODS: IL-22 levels in the serum and tissues of CRC patients were measured using enzyme-linked immunosorbent assay (ELISA). Cell counting kit-8 (CCK-8) assay was used to detect the viability of CRC (HCT116) cells treated with different IL-22 concentrations. Colony formation, Transwell invasion, and scratch assays were employed to assess the effects of IL-22 on cell proliferation, invasion, and migration. Western blotting was performed to measure the expression levels of phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), p-PI3K, p-AKT, E-cadherin, matrix metalloproteinase (MMP)-2, MMP-9, SNAI1, and TWIST1 in HCT116 cells treated with IL-22 or a PI3K inhibitor. RESULTS: ELISA results showed that the expression of IL-22 was significantly increased in the serum and tissues of CRC patients compared to controls. IL-22 treatment increased cell viability and colony formation in a concentration-dependent manner and enhanced cell invasion and migration. Western blotting analysis revealed that IL-22 stimulation upregulated p-PI3K and p-AKT expression, while total PI3K and AKT levels remained unchanged. Additionally, IL-22 also decreased E-cadherin expression and increased the expression of MMP-2, MMP-9, SNAI1, and TWIST1. CONCLUSIONS: IL-22 activates the PI3K-AKT pathway and promotes HCT116 cell proliferation and metastasis. Targeting the regulation of the PI3K/AKT pathway may be a potential therapeutic strategy for CRC.

18.
World J Gastrointest Oncol ; 16(6): 2504-2519, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38994160

RESUMO

BACKGROUND: Although the combination of lenvatinib and PD-1 inhibitors has become the standard regimen for the treatment of advanced hepatocellular carcinoma (HCC), real data on the impact of baseline hepatitis B virus (HBV)-DNA levels on the clinical efficacy of this regimen is still limited. AIM: To evaluate the effectiveness of camrelizumab combined with lenvatinib in patients with HCC at varying levels of HBV-DNA. METHODS: One hundred and twenty patients with HCC who received camrelizumab and lenvatinib treatment were categorized into two cohorts: HBV-DNA ≤ 2000 (n = 66) and HBV-DNA > 2000 (n = 54). The main outcomes measured were overall survival (OS) and progression-free survival (PFS), while additional outcomes included the rate of objective response rate (ORR), disease control rate (DCR), and any negative events. Cox proportional hazards regression analysis revealed independent predictors of OS, leading to the creation of a nomogram incorporating these variables. RESULTS: The median PFS was 8.32 months for the HBV-DNA ≤ 2000 group, which was similar to the 7.80 months observed for the HBV DNA > 2000 group (P = 0.88). Likewise, there was no notable variation in the median OS between the two groups, with durations of 13.30 and 14.20 months respectively (P = 0.14). The ORR and DCR were compared between the two groups, showing ORR of 19.70% vs 33.33% (P = 0.09) and DCR of 72.73% vs 74.07% (P = 0.87). The nomogram emphasized the importance of antiviral treatment as the main predictor of patient results, with portal vein tumor thrombus and Barcelona Clinic Liver Cancer staging following closely behind. CONCLUSION: The clinical outcomes of patients with HBV-associated HCC treated with camrelizumab in combination with lenvatinib are not significantly affected by HBV viral load.

19.
World J Clin Cases ; 12(21): 4717-4725, 2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-39070850

RESUMO

BACKGROUND: Abdominal aortitis can induce aneurysms, and tumor rupture can lead to organ ischemia or even sudden death. At present, there is a lack of extensive understanding and identification of key problems in the treatment of abdominal aortitis, which needs to be further analyzed using bibliometric analysis. AIM: To discuss the research hotspot and development trend of abdominal aortitis treatment. METHODS: We searched the English literature (published from January 1, 2000 to March 12, 2024) on the treatment of abdominal aortitis in the Web of Science database. Then, we identified and screened duplicate literature using CiteSpace 6.1R2 software. We conducted an analysis of the number of papers, a co-occurrence analysis of the authors and institutions, and co-occurrence and cluster analyses of the keywords. Then, we drew the author, institution, and keywords of the studies into graphs for visualization. Finally, we expounded on the author, institutional network interactions, and hot keywords of the studies on the treatment of abdominal aortitis. RESULTS: We included 210 English literature articles involving 190 authors; the author cooperation team was mainly represented by Caradu Caroline, Berard Xavier, Lu Guanyi, Harada Kenichi, and Sharma Ashish K. In the keyword analysis, high-frequency keywords include abdominal aortic aneurysm (38), abdominal aorta (24), Takayasu arteritis (22), etc. The three most central keywords were disease (0.69), classification (0.68), and abdominal aortic aneurysm (0.55). The first nine clusters of keywords are case report, abdominal aortic aneurysm, Takayasu arteritis, dyspnea hematuria, aortic elastic, IgG4-related disease, report, mid aortic dysplastic syndrome, and statin. In the keyword emergent analysis, 14 emergent words were obtained. Among them, seven keywords with strong abruptness were Takayasu arteritis, abdominal aortic aneurysm, disease, retroperitoneal fibrosis, expression, management, and large vessel vasculitis. In the past 3 years, the incidences of abdominal aortic aneurysm (intensity: 4.62) and inflammation (intensity: 1.99) were higher. CONCLUSION: The number of published papers is on the increase, but the cooperation among authors is scattered. The research focus is mainly on the pathogenesis and treatment of abdominal aortitis-related diseases.

20.
Angew Chem Int Ed Engl ; : e202404599, 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39023389

RESUMO

Spatiotemporally controlled two-photon photodegradation of hydrogels has gained increasing attention for high-precision subtractive tissue engineering. However, conventional photolabile hydrogels often have poor efficiency upon two-photon excitation in the near-infrared (NIR) region and thus require high laser dosage that may compromise cell activity. As a result, high-speed two-photon hydrogel erosion in the presence of cells remains challenging. Here we introduce the design and synthesis of efficient coumarin-based photodegradable hydrogels to overcome these limitations. A set of photolabile coumarin-functionalized polyethylene glycol linkers are synthesized through a Passerini multicomponent reaction. After mixing these linkers with thiolated hyaluronic acid, semi-synthetic photodegradable hydrogels are formed in situ via Michael addition crosslinking. The efficiency of photodegradation in these hydrogels is significantly higher than that in nitrobenzyl counterparts upon two-photon irradiation at 780 nm. A complex microfluidic network mimicking the bone microarchitecture is successfully fabricated in preformed coumarin hydrogels at high speeds of up to 300 mm s-1 and low laser dosage down to 10 mW. Further, we demonstrate fast two-photon printing of hollow microchannels inside a hydrogel to spatiotemporally direct cell migration in 3D. Collectively, these hydrogels may open new avenues for fast laser-guided tissue fabrication at high spatial resolution.

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