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BACKGROUND: Despite the growing research on 3D printing (3DP) in cardio-thoracic diseases, comprehensive bibliometric analyses remain scarce. This study aims to bridge this gap by identifying key research trends and hotspots within the field. METHODS: A bibliometric analysis was conducted on publications from 1991 to 2024 using data from the Web of Science Core Collection, with analysis performed using VOSviewer, CiteSpace, and the R package 'bibliometrix'. RESULTS: The analysis included 2,836 documents authored by 14,206 researchers across 85 countries. A significant rise in annual publications was observed, with the United States, China, and the United Kingdom leading in contributions. Prominent institutions, including Stanford University, were highlighted, while Scientific Reports and Biomaterials were identified as influential journals. Key research areas encompass cardiovascular, lung, and breast diseases, along with chest wall reconstructions, with emerging trends focusing on advanced materials for drug delivery and tissue engineering. CONCLUSION: This comprehensive bibliometric analysis of 3DP in cardio-thoracic diseases reveals global research trends, emerging themes, and the crucial role of 3DP in advancing medical education and personalized treatment, highlighting areas for future research and development.
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Rapid characterization of solid waste using near-infrared hyperspectral imaging (HSI) coupled with machine learning models has been increasingly investigated to replace the traditional time- and labor-intensive methods. However, contamination by waste-derived leachates or other fractions etc., can cause the spectra evolutions and significantly influences the identification performance, which has not been investigated before. The first attempt was made by using hyperspectral unmixing (HU) to extract the endmember components and demonstrate their contributions (abundance) to solid waste, taking the non-linear reflectance changes due to the O-H vibration of water and unclear variation associated with oil and leachates as an example. The HSI spectra of various solid waste components influenced by pure water, oil and three kinds of leachates were acquired. A novel method based on HU models, including multivariate curve resolution with alternating least squares and state-of-the-art autoencoder architectures (deep learning models), was developed to estimate the spectra of endmembers as well as their abundances in individual pixel. Their spatial distribution overview in solid waste was then yielded. The selected models were validated via an independent test data set, with lower spectral angle distance, 12.3° ± 6.5°, indicating the similarity of the predicted endmembers with real components. And the lowest root of mean square error on endmember distribution maps was 0.17. The non-linear liquid's effects by water and oil on spectra variations of solid waste were clearly illuminated. Additionally, the proposed method can extract information from mixed spectroscopic images and generate reconstructed spectra.
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Human epidermal growth factor receptor 2 (HER2) expression is one of the most important pathological characteristics of gastric cancer. The positive rate of HER2 expression in patients with gastric cancer is approximately 20%. The phase III Keynote-811 study revealed that anti-HER2 and anti-PD-1 therapy combined with chemotherapy could significantly improve the objective response rate as first-line treatment in patients with HER2-positive advanced gastric cancer. In the present study, we aimed to evaluate the efficacy of combination therapy with trastuzumab and PD-1 inhibitors in patients with advanced HER2-positive gastric cancer in a real-world setting. Seventy-two HER2-positive gastric cancer patients from three hospitals in China were retrospectively reviewed. These patients were treated with trastuzumab plus one anti-PD-1 agent with or without chemotherapy. The overall response rate, progression-free survival and overall survival were assessed according to the Response Evaluation Criteria in Solid Tumours (RECIST 1.1). From January 2018 to October 2021, 72 patients with HER2-positive gastric cancer received trastuzumab and a PD-1 inhibitor with or without chemotherapy as neoadjuvant chemotherapy, first-line therapy, second-line therapy or salvage therapy. The ORR was 54.2% for all patients and 79.4% for previously untreated patients. The median PFS and median OS were 10 months (95% CI: 8-13 months) and 26.1 months (95% CI: 18.5-NA months), respectively, for all patients. Grade 3 adverse effects occurred in approximately 25% of patients. Immune-related adverse effects occurred in approximately 12.5% of patients. Trastuzumab and PD-1 inhibitor combination therapy with or without chemotherapy achieved satisfactory survival outcomes in patients with HER2-positive gastric cancer with acceptable safety.
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Receptor de Morte Celular Programada 1 , Receptor ErbB-2 , Neoplasias Gástricas , Trastuzumab , Humanos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Neoplasias Gástricas/mortalidade , Receptor ErbB-2/metabolismo , Receptor ErbB-2/antagonistas & inibidores , Feminino , Pessoa de Meia-Idade , Masculino , Estudos Retrospectivos , Idoso , Trastuzumab/uso terapêutico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/metabolismo , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/efeitos adversos , Resultado do Tratamento , Idoso de 80 Anos ou maisRESUMO
INTRODUCTION AND AIMS: The histological and morphological differences in soft tissue between natural teeth and peri-implant may result in different clinical effectiveness to free gingival graft (FGG). This research aims to investigate the different efficacy of FGG in augmenting keratinized tissue width (KTW) between tooth and implant sites while evaluating its medium-term stability over a 2- to 5-year follow-up. METHODS: In this study, 29 patients underwent FGG to address insufficient clinical scenarios when KTW <2 mm at the buccal aspect, including 37 implant sites and 33 natural teeth sites both in posterior regions were included. The KTW and gingival margin position (GMP) of these sites was assessed by measuring the intra-oral photographs which were taken at 0 days (T0), 3-month (T1), 6-month (T2), 12-month post-surgery (T3), and 2 to 5 years follow-up (T4). RESULTS: The results revealed that KTW increased significantly in both groups. However, the natural teeth group showed significantly less graft shrinkage (GS) than the implants group. (Teeth: 2.05 ± 0.51 mm and 25.42% ± 6.45%; Implants: 3.18 ± 0.65 mm and 38.92% ± 5.39%, P <.01). From T1 to T4. The gingival margin coronally advanced by 0.47 ± 0.51 mm and 0.18 ± 0.43 mm for the natural teeth and implants group, respectively (P<.05). CONCLUSIONS: A greater KTW reduction after FGG was observed at implants versus natural teeth. And, the graft surrounding implants after crown restoration was stable for up to 2 to 5 years. CLINICAL RELEVANCE: By comparing the changes in KTW around natural teeth and implants following FGG to investigate whether there are differences between them and the degree of differences. Additionally, this allows us to explore whether the restorations impact the effect of FGG. This research can assist clinicians in selecting an appropriate amount of soft tissue during surgery to achieve treatment goals, reduce postoperative discomfort for patients, and enhance predictability in clinicians' ability to increase keratinized tissue. Furthermore, by observing changes in the position of GMP around natural teeth and implants, the effectiveness of FGG in root coverage can be understood, thus improving the predictability of FGG for root coverage.
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OBJECTIVE: To investigate the current situation and influencing factors of postoperative nausea and vomiting (PONV) in lung cancer patients undergoing thoracoscopic surgery under general anesthesia, providing a reference for developing targeted PONV prevention and management strategies. METHODS: Using a consecutive sampling method, 200 lung cancer patients who underwent their first thoracoscopic surgery under general anesthesia between November 18, 2021, and March 1, 2022, at a tertiary class A cancer hospital in Liaoning Province, China, were selected. The occurrence of PONV within 24 h post-operation was assessed using WHO Postoperative Nausea and Vomiting Rating Criteria. Patient general information, surgical and medication data were systematically collected to analyze the independent influencing factors of PONV. RESULTS: Among the 200 patients undergoing thoracoscopic lung cancer surgery under general anesthesia, 75 (37.5%) experienced PONV. Logistic regression analysis indicated that being female, having a history of motion sickness, and a history of PONV were independent risk factors for the occurrence of PONV in these patients. Long-acting antiemetics such as penehyclidine hydrochloride and methylprednisolone were protective factors against PONV. CONCLUSION: The incidence of PONV in patients undergoing thoracoscopic lung cancer surgery under general anesthesia is relatively high. Nursing staff should focus on female patients and those with a history of motion sickness and PONV. Comprehensive preoperative assessments should be conducted, exploring multimodal analgesia and applying integrated prevention measures to reduce the occurrence of PONV and promote the rapid recovery of patients.
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Anestesia Geral , Neoplasias Pulmonares , Náusea e Vômito Pós-Operatórios , Toracoscopia , Humanos , Feminino , Masculino , Náusea e Vômito Pós-Operatórios/epidemiologia , Náusea e Vômito Pós-Operatórios/etiologia , Náusea e Vômito Pós-Operatórios/prevenção & controle , Neoplasias Pulmonares/cirurgia , Pessoa de Meia-Idade , Anestesia Geral/efeitos adversos , Idoso , Fatores de Risco , Toracoscopia/métodos , Incidência , China/epidemiologia , Antieméticos/uso terapêutico , AdultoRESUMO
Objective: This review aims to summarize existing interventions from the international literature addressing fertility concerns in cancer patients, providing theoretical and practical guidance for future interventions. Methods: In September 2023, a systematic search covering 13 databases was conducted using the methodology outlined by the Joanne Briggs Institute for a comprehensive systematic review. This search identified published English and Chinese-language papers. Results: A total of 20 studies meeting inclusion criteria were included in this review. The studies predominantly originated in China and the United States. A comprehensive synthesis of interventions from the included literature across three dimensions and seven aspects was conducted. The interventions primarily focused on psychological interventions and web-based self-help tools for patients. The Reproductive Concerns After Cancer Scale (RCAC) was the primary assessment tool employed. Conclusion: Addressing fertility concerns in cancer patients is a complex issue involving various stakeholders and diverse intervention strategies. Lessons from international research can inform the development of context-specific interventions tailored to individual needs.
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This study aimed to investigate the effects and potential mechanism of Polygonati Rhizoma aqueous extract on chronic obstructive pulmonary disease(COPD) in rats. Forty-eight Sprague-Dawley rats were randomly assigned to the normal, model,Yupingfeng Granules(1. 5 g·kg~(-1)), and low-, medium-, and high-dose(0. 25, 0. 5, and 1 g·kg~(-1), respectively) Polygonati Rhizoma aqueous extract groups. The rat model of COPD was established by cigarette smoke inhalation for 8 weeks, and then the modeled rats received corresponding treatment for 4 weeks. The grip strength and fecal moisture content were measured, and the lung index was calculated. Enzyme-linked immunosorbent assay(ELISA) was employed to determine the levels of interleukin(IL)-6 and tumor necrosis factor(TNF)-α in the lung tissue. Hematoxylin-eosin(HE) staining and Masson staining were performed to assess the pathological changes in the lung tissue. Flow cytometry was used to analyze T lymphocytes and their subpopulations in the peripheral blood, and the immunofluorescence assay and Western blot were employed to measure the protein levels of Toll-like receptor 4(TLR4), phosphorylated nuclear factor-kappaB(p-NF-κB), NF-κB, phosphorylated inhibitory kappa B-α(p-IκBα), IκBα, IL-6,and TNF-α in the lung tissue. The results indicated that the treatment with Polygonati Rhizoma aqueous extract significantly reduced the fecal moisture content, enhanced the grip strength, and inhibited inflammatory infiltration and fibrosis in the lung tissue. The treatment increased the Th/Tc ratio and Th cell proportion and decreased the Tc cell proportion in the peripheral blood. Furthermore,the treatment down-regulated the expression levels of TLR4, IL-6, and TNF-α and the p-NF-κB/NF-κB and p-IκBα/IκBα ratios in the lung tissue. In conclusion, Polygonati Rhizoma aqueous extract can ameliorate lung tissue damage in the rat model of COPD by inhibiting the TLR4/NF-κB signaling pathway and the production of inflammatory mediators.
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Medicamentos de Ervas Chinesas , Pulmão , NF-kappa B , Polygonatum , Doença Pulmonar Obstrutiva Crônica , Ratos Sprague-Dawley , Rizoma , Receptor 4 Toll-Like , Animais , Ratos , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/química , Masculino , Polygonatum/química , NF-kappa B/metabolismo , NF-kappa B/genética , Receptor 4 Toll-Like/metabolismo , Receptor 4 Toll-Like/genética , Pulmão/efeitos dos fármacos , Rizoma/química , Interleucina-6/genética , Interleucina-6/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Fator de Necrose Tumoral alfa/genética , HumanosRESUMO
BACKGROUND: The combination of immunotherapy and antiangiogenic therapy has shown potential in the treatment of numerous malignant tumors, but limited evidence was available for soft tissue sarcomas (STS). Therefore, the aim of the present study is to assess the efficacy and safety of immunotherapy in conjunction with antiangiogenic therapy in patients diagnosed with advanced STS (aSTS). METHODS: The study enrolled patients with aSTS from January 2014 to October 2022. Eligible participants had previously received anthracycline-based chemotherapy, presented with an anthracycline-resistant sarcoma subtype, or were ineligible for anthracycline treatment due to medical conditions. Following enrollment, these patients received a combination of immunotherapy and antiangiogenic therapy. The primary endpoints were the objective response rate (ORR) and progression-free survival (PFS), while the secondary endpoints included the disease control rate (DCR), overall survival (OS), and the incidence of adverse events. RESULTS: Fifty-one patients were included in this cohort study. The median duration of follow-up was 15.8 months. The ORR and DCR were 17.6%, and 76.5%, respectively. The median PFS (mPFS) was 5.8 months (95% CI: 4.8-6.8) for all patients, and the median OS had not been reached as of the date cutoff. Multivariate analysis indicated that Eastern Cooperative Oncology Group performance status of 0-1 and ≤ second-line treatment were positive predictors for both PFS and OS. Patients with alveolar soft part sarcoma or clear cell sarcoma had longer mPFS (16.2 months, 95% CI: 7.8-25.6) when compared to those with other subtypes of STS (4.4 months, 95% CI: 1.4-7.5, P < 0.001). Among the observed adverse events, hypertension (23.5%), diarrhea (17.6%), and proteinuria (17.6%) were the most common, with no treatment-related deaths reported. CONCLUSION: The combination of immunotherapy and antiangiogenic agents showed promising efficacy and acceptable toxicity in patients with aSTS, especially those with alveolar soft part sarcoma or clear cell sarcoma.
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Inibidores da Angiogênese , Imunoterapia , Sarcoma , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Inibidores da Angiogênese/uso terapêutico , Inibidores da Angiogênese/efeitos adversos , Inibidores da Angiogênese/administração & dosagem , Adulto , Sarcoma/tratamento farmacológico , Sarcoma/terapia , Sarcoma/mortalidade , Sarcoma/patologia , Idoso , Imunoterapia/métodos , Imunoterapia/efeitos adversos , Resultado do Tratamento , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Intervalo Livre de Progressão , Adulto Jovem , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/efeitos adversosRESUMO
BACKGROUND: Diabetic nephropathy (DN) is a major contributor to chronic kidney disease. This study aims to identify immune biomarkers and potential therapeutic drugs in DN. METHODS: We analyzed two DN microarray datasets (GSE96804 and GSE30528) for differentially expressed genes (DEGs) using the Limma package, overlapping them with immune-related genes from ImmPort and InnateDB. LASSO regression, SVM-RFE, and random forest analysis identified four hub genes (EGF, PLTP, RGS2, PTGDS) as proficient predictors of DN. The model achieved an AUC of 0.995 and was validated on GSE142025. Single-cell RNA data (GSE183276) revealed increased hub gene expression in epithelial cells. CIBERSORT analysis showed differences in immune cell proportions between DN patients and controls, with the hub genes correlating positively with neutrophil infiltration. Molecular docking identified potential drugs: cysteamine, eltrombopag, and DMSO. And qPCR and western blot assays were used to confirm the expressions of the four hub genes. RESULTS: Analysis found 95 and 88 distinctively expressed immune genes in the two DN datasets, with 14 consistently differentially expressed immune-related genes. After machine learning algorithms, EGF, PLTP, RGS2, PTGDS were identified as the immune-related hub genes associated with DN. In addition, the mRNA and protein levels of them were obviously elevated in HK-2 cells treated with glucose for 24 h, as well as their mRNA expressions in kidney tissues of mice with DN. CONCLUSION: This study identified 4 hub immune-related genes (EGF, PLTP, RGS2, PTGDS), as well as their expression profiles and the correlation with immune cell infiltration in DN.
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Nefropatias Diabéticas , Aprendizado de Máquina , Nefropatias Diabéticas/genética , Nefropatias Diabéticas/tratamento farmacológico , Humanos , Animais , Camundongos , Proteínas RGS/genética , Perfilação da Expressão Gênica , Simulação de Acoplamento Molecular , AlgoritmosRESUMO
Background: Growing evidence suggests that endometriosis (EMs) is a risk factor for endometriosis-associated ovarian cancer (EAOC). The aim was to identify and validate gene signatures associated with EMs that may serve as potential biomarkers for evaluating the prognosis of patients with EAOC. Methods: The data of EMs and control samples was obtained from GEO database. The weighted gene co-expression network analysis (WGCNA) identified modular genes significantly associated with EMs. The KEGG pathway and GO functional enrichment analyses were also performed. Univariate Cox regression analysis was conducted to screen marker genes associated with the prognosis of EAOC patients. Finally, RT-qPCR and immunohistochemical verified the expression of ADAMTS19 and TUBB in normal ovarian and EAOC tissues, and the biological functions of ADAMTS19 and TUBB were preliminarily explored by CCK8 and Transwell assays. Results: The WGCNA identified 2 co-expression modules, which in total included 615 genes, and 7642 differentially expressed genes (DEGs) were detected thorough analysis of the EAOC dataset. After taking the intersection of 615 modular genes and 7642 DEGs, 214 shared genes were obtained, and univariate COX regression analysis pointed 10 genes associated with the prognosis of EAOC. Moreover, it was demonstrated by RT-qPCR and immunohistochemical staining experiments that ADAMTS19 expression was elevated, while TUBB expression was reduced in EAOC compared with normal ovarian cells and tissues. Finally, cell experiments revealed that ADAMTS19 promoted the proliferation and invasion in EAOC cells, while overexpression of TUBB inhibited these processes. Conclusions: The present study identified and validated new EMs-associated gene markers, which could serve as potential biomarkers for assessing the prognostic risk of EAOC patients. In addition, some of these genes may have significance as novel therapeutic targets and could be used to guide clinical applications.
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Biomarcadores Tumorais , Endometriose , Regulação Neoplásica da Expressão Gênica , Neoplasias Ovarianas , Humanos , Feminino , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/diagnóstico , Endometriose/genética , Endometriose/complicações , Endometriose/patologia , Prognóstico , Biomarcadores Tumorais/genética , Proteínas ADAMTS/genética , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Tubulina (Proteína)/genética , Tubulina (Proteína)/metabolismo , Proliferação de Células/genética , Adulto , Linhagem Celular TumoralRESUMO
Oxygen toxicity constitutes a key contributor to bronchopulmonary dysplasia (BPD). Critical step in the pathogenesis of BPD is the inflammatory response in the immature lung with the release of pro-inflammatory cytokines and the influx of innate immune cells. Identification of efficient therapies to alleviate the inflammatory response remains an unmet research priority. First, we studied macrophage and neutrophil profiles in tracheal aspirates of n = 103 preterm infants <29 weeks´ gestation requiring mechanical ventilation. While no differences were present at birth, a higher fraction of macrophages, the predominance of the CD14+CD16+ subtype on day 5 of life was associated with moderate/severe BPD. Newborn CCL-2-/- mice insufficient in pulmonary macrophage recruitment had a reduced influx of neutrophils, lower apoptosis induction in the pulmonary tissue and better-preserved lung morphometry with higher counts of type II cells, mesenchymal stem cells and vascular endothelial cells when exposed to hyperoxia for 7 days. To study the benefit of a targeted approach to prevent the pulmonary influx of macrophages, wildtype mice were repeatedly treated with CCL-2 blocking antibodies while exposed to hyperoxia for 7 days. Congruent with the results in CCL-2-/- animals, the therapeutic intervention reduced the pulmonary inflammatory response, attenuated cell death in the lung tissue and better-preserved lung morphometry. Overall, our preclinical and clinical datasets document the predominant role of macrophage recruitment to the pathogenesis of BPD and establish the abrogation of CCL-2 function as novel approach to protect the immature lung from hyperoxic injury.
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BACKGROUND: The distal aspect of the second molar (d-M2) often exhibits infrabony defects due to the adjacent third molar. Although the defects can be treated by guided tissue regeneration (GTR) after removing the third molar, the optimal timing remains uncertain following third molar removal in clinical decision-making. This study aimed to compare delayed and immediate GTR treatments to assist in clinical decision-making. METHODS: D-M2 infrabony defects with a minimum 1-year follow-up were collected and divided into three groups: Immediate GTR group, which underwent third molar extraction and received GTR simultaneously; Delayed GTR group, which underwent delayed GTR at least 3 months after third molar extraction; and Control group, which underwent only scaling and root planing during third molar extraction. The clinical and radiographic parameters related to the infrabony defect before GTR and post-surgery were evaluated using the Kruskal-Wallis test or one-way ANOVA, followed by post-hoc Dunn's test or the Bonferroni test for pairwise comparisons. RESULTS: A total of 109 d-M2 infrabony defects were assessed. No significant differences were found between the two GTR groups, although both of them showed significant reductions in infrabony defect depth: the immediate GTR group (2.77 ± 1.97 mm vs. 0.68 ± 1.03 mm, p < 0.001) and the delayed GTR group (2.98 ± 1.08 mm vs. 0.68 ± 1.03 mm, p < 0.001) compared to the control group. CONCLUSION: GTR can effectively improve d-M2 infrabony defects when the third molar is removed, whether simultaneously or delayed. Patients may experience less discomfort with immediate GTR treatment as it requires only one surgery.
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Regeneração Tecidual Guiada Periodontal , Dente Serotino , Dente Molar , Extração Dentária , Humanos , Dente Serotino/cirurgia , Estudos Retrospectivos , Masculino , Feminino , Adulto , Regeneração Tecidual Guiada Periodontal/métodos , Dente Molar/cirurgia , Perda do Osso Alveolar/cirurgia , Perda do Osso Alveolar/diagnóstico por imagem , Fatores de Tempo , Pessoa de Meia-Idade , Adulto JovemRESUMO
BACKGROUND: Chronic obstructive pulmonary disease (COPD) remains a leading cause of morbidity and mortality worldwide, characterized by persistent respiratory symptoms and airflow limitation. The involvement of C-C motif chemokine ligand 2 (CCL2) in COPD pathogenesis, particularly in macrophage regulation and activation, is poorly understood despite its recognized role in chronic inflammation. Our study aims to elucidate the regulatory role and molecular mechanisms of CCL2 in the pathogenesis of COPD, providing new insights for therapeutic strategies. METHODS: This study focused on the CCL2-CCR2 signaling pathway, exploring its role in COPD pathogenesis using both Ccl2 knockout (KO) mice and pharmacological inhibitors. To dissect the underlying mechanisms, we employed various in vitro and in vivo methods to analyze the secretion patterns and pathogenic effects of CCL2 and its downstream molecular signaling through the CCL2-CCR2 axis. RESULTS: Elevated Ccl2 expression was confirmed in the lungs of COPD mice and was associated with enhanced recruitment and activation of macrophages. Deletion of Ccl2 in knockout mice, as well as treatment with a Ccr2 inhibitor, resulted in protection against CS- and LPS-induced alveolar injury and airway remodeling. Mechanistically, CCL2 was predominantly secreted by bronchial epithelial cells in a process dependent on STAT1 phosphorylation and acted through the CCR2 receptor on macrophages. This interaction activated the PI3K-AKT signaling pathway, which was pivotal for macrophage activation and the secretion of inflammatory cytokines, further influencing the progression of COPD. CONCLUSIONS: The study highlighted the crucial role of CCL2 in mediating inflammatory responses and remodeling in COPD. It enhanced our understanding of COPD's molecular mechanisms, particularly how CCL2's interaction with the CCR2 activates critical signaling pathways. Targeting the CCL2-CCR2 axis emerged as a promising strategy to alleviate COPD pathology.
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Quimiocina CCL2 , Macrófagos , Camundongos Knockout , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Doença Pulmonar Obstrutiva Crônica , Receptores CCR2 , Transdução de Sinais , Doença Pulmonar Obstrutiva Crônica/metabolismo , Doença Pulmonar Obstrutiva Crônica/patologia , Animais , Quimiocina CCL2/metabolismo , Quimiocina CCL2/genética , Receptores CCR2/metabolismo , Receptores CCR2/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Macrófagos/metabolismo , Macrófagos/efeitos dos fármacos , Camundongos , Humanos , Camundongos Endogâmicos C57BL , MasculinoRESUMO
Background: Myofibroblasts (MYFs) are generally considered the principal culprits in excessive extracellular matrix deposition and scar formation in the pathogenesis of lung fibrosis. Lipofibroblasts (LIFs), on the other hand, are defined by their lipid-storing capacity and are predominantly found in the alveolar regions of the lung. They have been proposed to play a protective role in lung fibrosis. We previously reported that a LIF to MYF reversible differentiation switch occurred during fibrosis formation and resolution. In this study, we tested whether WI-38 cells, a human embryonic lung fibroblast cell line, could be used to study fibroblast differentiation towards the LIF or MYF phenotype and whether this could be relevant for idiopathic pulmonary fibrosis (IPF). Methods: Using WI-38 cells, Fibroblast (FIB) to MYF differentiation was triggered using TGF-ß1 treatment and FIB to LIF differentiation using Metformin treatment. We also analyzed the MYF to LIF and LIF to MYF differentiation by pre-treating the WI-38 cells with TGF-ß1 or Metformin respectively. We used IF, qPCR and bulk RNA-Seq to analyze the phenotypic and transcriptomic changes in the cells. We correlated our in vitro transcriptome data from WI-38 cells (obtained via bulk RNA sequencing) with the transcriptomic signature of LIFs and MYFs derived from the IPF cell atlas as well as with our own single-cell transcriptomic data from IPF patients-derived lung fibroblasts (LF-IPF) cultured in vitro. We also carried out alveolosphere assays to evaluate the ability of the proposed LIF and MYF cells to support the growth of alveolar epithelial type 2 cells. Results: WI-38 cells and LF-IPF display similar phenotypical and gene expression responses to TGF-ß1 and Metformin treatment. Bulk RNA-Seq analysis of WI-38 cells and LF-IPF treated with TGF-ß1, or Metformin indicate similar transcriptomic changes. We also show the partial conservation of the LIF and MYF signature extracted from the Habermann et al. scRNA-seq dataset in WI-38 cells treated with Metformin or TGF-ß1, respectively. Alveolosphere assays indicate that LIFs enhance organoid growth, while MYFs inhibit organoid growth. Finally, we provide evidence supporting the MYF to LIF and LIF to MYF reversible switch using WI-38 cells. Conclusions: WI-38 cells represent a versatile and reliable model to study the intricate dynamics of fibroblast differentiation towards the MYF or LIF phenotype associated with lung fibrosis formation and resolution, providing valuable insights to drive future research.
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Diferenciação Celular , Fibroblastos , Fibrose Pulmonar Idiopática , Miofibroblastos , Fator de Crescimento Transformador beta1 , Humanos , Miofibroblastos/metabolismo , Fibroblastos/metabolismo , Linhagem Celular , Fibrose Pulmonar Idiopática/patologia , Fibrose Pulmonar Idiopática/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Fator de Crescimento Transformador beta1/genética , Pulmão/patologia , Pulmão/citologia , Transcriptoma , Metformina/farmacologia , Plasticidade Celular/efeitos dos fármacos , FenótipoRESUMO
The discovery of novel antitumor agents derived from natural plants is a principal objective of anticancer drug research. Frankincense, a widely recognized natural antitumor medicine, has undergone a systematic review encompassing its species, chemical constituents, and diverse pharmacological activities and mechanisms. The different species of frankincense include Boswellia serrata, Somali frankincense, Boswellia frereana, and Boswellia arabica. Various frankincense extracts and compounds exhibit antitumor, anti-inflammatory, and hepatoprotective properties and antioxidation, memory enhancement, and immunological regulation capabilities. They also have comprehensive effects on regulating flora. Frankincense and its principal chemical constituents have demonstrated promising chemoprophylactic and therapeutic abilities against tumors. This review provides a systematic summary of the mechanism of action underlying the antitumor effects of frankincense and its major constituents, thus laying the foundations for developing effective tumor-combating targets.
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Franquincenso , Humanos , Franquincenso/química , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Neoplasias/tratamento farmacológico , Animais , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Extratos Vegetais/químicaRESUMO
INTRODUCTION: As proteins that promote immune cell differentiation, chemokines have attracted great interest regarding their role in anti-tumor immune responses within the cancer environment. However, the exact role of CXCL10, a chemokine, in bladder cancer (BLCA) is still not fully elucidated. METHOD: In the present study, we employed bioinformatics approaches to examine the expression pattern, prognostic value, and immune infiltration of CXCL10 in BLCA. Furthermore, we focused on examining the impact of CXCL10 on immune therapy in BLCA. Additionally, we validated the expression of CXCL10 in various BLCA cell lines using PCR techniques. RESULTS: We observed an upregulation of CXCL10 in BLCA tissues as well as in different cell lines. Additionally, upregulation of CXCL10 indicates a better prognosis for BLCA patients. ESTIMATE and CIBERSORT algorithms suggest that CXCL10 is closely associated with the immune microenvironment of BLCA. Through multiple immune therapy cohorts, we also identified that CXCL10 has shown promising predictive value for assessing the efficacy of immune therapy in in BLCA. CONCLUSION: Our study indicates that CXCL10 has the potential to serve as a favorable prognostic factor and is strongly associated with immune infiltration in BLCA.
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ETHNOPHARMACOLOGICAL RELEVANCE: Polycystic ovary syndrome (PCOS) is a common endocrine disorder associated with reproductive dysfunction and metabolic abnormalities, particularly characterized by insulin resistance and chronic low-grade inflammation. Multiple clinical studies have clearly demonstrated the significant efficacy and safety of the combination of Bailing capsules (BL) in the treatment of PCOS, but its pharmacological effects and mechanisms still require further study. AIM OF THE STUDY: To evaluate the effect of BL on improving PCOS in mice and explore the mechanism. METHODS: In this study, Dehydroepiandrosterone (DHEA) injection was administered alone and in combination with a high-fat and high-sugar diet to induce PCOS-like mouse. They were randomly divided into five groups: normal group (N), PCOS group (P), Bailing capsule low-dose group (BL-L), Bailing capsule high-dose group (BL-H) and Metformin + Daine-35 group (M + D). Firstly, the effects of BL on ovarian lesions, serum hormone levels, HOMA-IR, intestinal barrier function, inflammation levels, along with the expression of IRS1, PI3K, AKT, TLR4, Myd88, NF-κB p65, TNF-α, IL-6, and Occludin of the ovary, liver and colon were investigated. Finally, the composition of the gut microbiome of fecal was tested. RESULTS: The administration of BL significantly reduced body weight, improved hormone levels, improved IR, and attenuated pathological damage to ovarian tissues, up-regulated the expression of IRS1, PI3K, and AKT in liver. It also decreased serum LPS, TNF-α, and IL-6 levels, while downregulating the expression of Myd88, TLR4, and NF-κB p65. Additionally, BL improved intestinal barrier damage and upregulated the expression of Occludin. Interestingly, the abundance of norank_f__Muribaculacea and Lactobacillus was down-regulated, while the abundance of Akkermansia was significantly up-regulated. CONCLUSION: The results of the study showed that BL exerts a treatment PCOS effect, which may be related to the modulation of the gut microbiota, the improvement of insulin resistance and the intestinal-derived LPS-TLR4 inflammatory pathway. Our research will provide a theoretical basis for the clinical treatment of PCOS.
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Medicamentos de Ervas Chinesas , Lipopolissacarídeos , Síndrome do Ovário Policístico , Transdução de Sinais , Receptor 4 Toll-Like , Síndrome do Ovário Policístico/tratamento farmacológico , Síndrome do Ovário Policístico/induzido quimicamente , Animais , Feminino , Receptor 4 Toll-Like/metabolismo , Camundongos , Transdução de Sinais/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Resistência à Insulina , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Desidroepiandrosterona/farmacologia , Cápsulas , Intestinos/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Ovário/efeitos dos fármacos , Ovário/metabolismo , Ovário/patologiaRESUMO
Gasdermin D (GSDMD) is the common effector for cytokine secretion and pyroptosis downstream of inflammasome activation and was previously shown to form large transmembrane pores after cleavage by inflammatory caspases to generate the GSDMD N-terminal domain (GSDMD-NT)1-10. Here we report that GSDMD Cys191 is S-palmitoylated and that palmitoylation is required for pore formation. S-palmitoylation, which does not affect GSDMD cleavage, is augmented by mitochondria-generated reactive oxygen species (ROS). Cleavage-deficient GSDMD (D275A) is also palmitoylated after inflammasome stimulation or treatment with ROS activators and causes pyroptosis, although less efficiently than palmitoylated GSDMD-NT. Palmitoylated, but not unpalmitoylated, full-length GSDMD induces liposome leakage and forms a pore similar in structure to GSDMD-NT pores shown by cryogenic electron microscopy. ZDHHC5 and ZDHHC9 are the major palmitoyltransferases that mediate GSDMD palmitoylation, and their expression is upregulated by inflammasome activation and ROS. The other human gasdermins are also palmitoylated at their N termini. These data challenge the concept that cleavage is the only trigger for GSDMD activation. They suggest that reversible palmitoylation is a checkpoint for pore formation by both GSDMD-NT and intact GSDMD that functions as a general switch for the activation of this pore-forming family.
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Gasderminas , Lipoilação , Proteínas de Ligação a Fosfato , Espécies Reativas de Oxigênio , Animais , Feminino , Humanos , Masculino , Camundongos , Aciltransferases/metabolismo , Microscopia Crioeletrônica , Cisteína/metabolismo , Gasderminas/química , Gasderminas/metabolismo , Inflamassomos/metabolismo , Lipossomos/metabolismo , Lipossomos/química , Mitocôndrias/metabolismo , Proteínas de Ligação a Fosfato/química , Proteínas de Ligação a Fosfato/metabolismo , Piroptose , Espécies Reativas de Oxigênio/metabolismo , Células THP-1RESUMO
BACKGROUND: Both venetoclax plus a hypomethylating agent (VEN/HMA) and cytarabine, aclarubicin, and granulocyte colony-stimulating factor (CAG) are low-intensity regimens for older patients with acute myeloid leukemia (AML) that show good efficacy and safety. It is unknown how VEN/HMA compares with the CAG regimen for the treatment of newly diagnosed AML. METHODS: The outcomes of patients with newly diagnosed AML treated with VEN/HMA were compared with those of patients treated with a CAG-based regimen. Propensity score matching between these two cohorts at a 1:1 ratio was performed according to age at diagnosis, sex, Eastern Cooperative Oncology Group performance status, state of fitness, and European LeukemiaNet (ELN) 2022 risk stratification to minimize bias. RESULTS: A total of 84 of 96 patients in the VEN/HMA cohort were matched with 84 of 147 patients in the CAG cohort. VEN/HMA resulted in a better response than the CAG-based regimens, as indicated by a higher composite complete remission (CRc) rate (82.1% vs. 60.7%; p = .002) and minimal residual disease negativity rate (88.2% vs. 68.2%; p = .009). In patients with an ELN adverse risk, VEN/HMA was associated with a higher CRc rate compared to CAG (80.5% vs. 58.3%; p = .006). VEN/HMA was associated with longer event-free survival (EFS) (median EFS, not reached vs. 4.5 months; p = .0004), whereas overall survival (OS) was comparable between the two cohorts (median OS, not reached vs. 18 months; p = .078). CONCLUSIONS: The VEN/HMA regimen may result in a better response than CAG-based treatment in older patients with newly diagnosed AML.
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Aclarubicina , Protocolos de Quimioterapia Combinada Antineoplásica , Compostos Bicíclicos Heterocíclicos com Pontes , Citarabina , Fator Estimulador de Colônias de Granulócitos , Leucemia Mieloide Aguda , Pontuação de Propensão , Sulfonamidas , Humanos , Feminino , Masculino , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/mortalidade , Idoso , Citarabina/administração & dosagem , Citarabina/uso terapêutico , Aclarubicina/administração & dosagem , Aclarubicina/uso terapêutico , Pessoa de Meia-Idade , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Compostos Bicíclicos Heterocíclicos com Pontes/administração & dosagem , Sulfonamidas/administração & dosagem , Sulfonamidas/uso terapêutico , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Idoso de 80 Anos ou maisRESUMO
OBJECTIVE: This study aims to explore the intervention effects of narrative nursing on the reproductive concerns of cervical cancer patients of childbearing age undergoing surgical treatment. METHODS: Patients undergoing cervical cancer surgery with moderate to severe levels of reproductive concerns, treated between January and December 2023 at a tertiary Grade-A oncology hospital in China, were selected as the research subjects. Patients were randomized into an intervention group and a control group, each consisting of 33 patients. The control group received standard nursing care, while the intervention group received a narrative nursing intervention in addition to standard care. The changes in the levels of reproductive concerns, post-traumatic growth, and quality of life scores before and after the intervention were compared between the two groups. RESULTS: After the intervention, the reproductive concerns scores of the cervical cancer patients in the intervention group (32.53 ± 4.77) were significantly lower than those in the control group (59.29 ± 3.24), with a statistically significant difference (t = 26.143, p < 0.001). The post-traumatic growth scores in the intervention group (86.78 ± 3.52) were significantly higher than those in the control group (68.06 ± 6.24), with a statistically significant difference (t = -14.595, p < 0.001). The quality of life scores in the intervention group (149.00 [IQR = 8.75]) were significantly higher than those in the control group (129.00 [IQR = 13.00]), with a statistically significant difference (z = -5.799, p < 0.001). CONCLUSION: Narrative nursing can effectively alleviate reproductive concerns in cervical cancer patients undergoing surgical treatment, promote positive psychological changes post-trauma, and improve patients' quality of life.