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1.
BMJ Open Respir Res ; 11(1)2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38580439

RESUMO

BACKGROUND: Despite substantial progress in reducing the global burden of chronic obstructive pulmonary disease (COPD), traditional methods to promote understanding and management of COPD are insufficient. We developed an innovative model based on the internet of things (IoT) for screening and management of COPD in primary healthcare (PHC). METHODS: Electronic questionnaire and IoT-based spirometer were used to screen residents. We defined individuals with a questionnaire score of 16 or higher as high-risk population, COPD was diagnosed according to 2021 Global Initiative for COPD (Global Initiative for Chronic Obstructive Lung Disease) criteria. High-risk individuals and COPD identified through the screening were included in the COPD PHC cohort study, which is a prospective, longitudinal observational study. We provide an overall description of the study's design framework and baseline data of participants. RESULTS: Between November 2021 and March 2023, 162 263 individuals aged over 18 from 18 cities in China were screened, of those 43 279 high-risk individuals and 6902 patients with COPD were enrolled in the cohort study. In the high-risk population, the proportion of smokers was higher than that in the screened population (57.6% vs 31.4%), the proportion of males was higher than females (71.1% vs 28.9%) and in people underweight than normal weight (57.1% vs 32.0%). The number of high-risk individuals increased with age, particularly after 50 years old (χ2=37 239.9, p<0.001). Female patients are more common exposed to household biofuels (χ2=72.684, p<0.05). The majority of patients have severe respiratory symptoms, indicated by a CAT score of ≥10 (85.8%) or an Modified Medical Research Council Dyspnoea Scale score of ≥2 (65.5%). CONCLUSION: Strategy based on IoT model help improve the detection rate of COPD in PHC. This cohort study has established a large clinical database that encompasses a wide range of demographic and relevant data of COPD and will provide invaluable resources for future research.


Assuntos
Internet das Coisas , Doença Pulmonar Obstrutiva Crônica , Masculino , Humanos , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos de Coortes , Progressão da Doença , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/terapia , Atenção Primária à Saúde
2.
J Cancer Res Clin Oncol ; 150(4): 188, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38602568

RESUMO

BACKGROUND: We aimed to comprehensively analyze the clinical value of immune-related eRNAs-driven genes in lung adenocarcinoma (LUAD) and find the potential biomarkers for prognosis and therapeutic response to improve the survival of this malignant disease. MATERIALS AND METHODS: Pearson's correlation analysis was performed to identify the immune-related eRNAs-driven genes. Cox regression and least absolute shrinkage and selection operator (LASSO) analyses were used to construct this prognostic risk signature. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were used to investigate the underlying molecular mechanism. The single sample gene set enrichment analysis (ssGSEA) algorithm was conducted to evaluate the immune status based on the signature. The quantitative real-time PCR (qRT-PCR) analysis was performed to evaluate the expression value of the signature genes between LUAD tissues and adjacent lung tissues. RESULTS: Five immune-related eRNAs-driven genes (SHC1, GDF10, CCL14, FYN, and NOD1) were identified to construct a prognostic risk signature with favorable predictive capacity. The patients with high-risk scores based on the signature were significantly associated with the malignant clinical features compared with those with low-risk scores. Kaplan-Meier analysis demonstrated that the sample in the low-risk group had a prolonged survival compared with those in the high-risk group. This risk signature was validated to have a promising predictive capacity and reliability in diverse clinical situations and independent cohorts. The functional enrichment analysis demonstrated that humoral immune response and intestinal immune network for IgA production pathway might be the underlying molecular mechanism related to the signature. The proportion of the vast majority of immune infiltrating cells in the high-risk group was significantly lower than that in the low-risk group, and the immunotherapy response rate in the low-risk group was significantly higher than that in the high-risk group. Moreover, BI-2536, sepantronium bromide, and ULK1 were the potential drugs for the treatment of patients with higher risk scores. Finally, the experiment in vivo and database analysis indicated that CCL14, FYN, NOD1, and GDF10 are the potential LUAD suppressor and SHC1 is a potential treatment target for LUAD. CONCLUSION: Above all, we constructed a prognostic risk signature with favorable predictive capacity in LUAD, which was significantly associated with malignant features, immunosuppressive tumor microenvironment, and immunotherapy response and may provide clinical benefit in clinical decisions.

4.
Respiration ; 103(3): 134-145, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38382478

RESUMO

BACKGROUND: Early detection and accurate diagnosis of pulmonary nodules are crucial for improving patient outcomes. While surgical resection of malignant nodules is still the preferred treatment option, it may not be feasible for all patients. We aimed to discuss the advances in the treatment of pulmonary nodules, especially stereotactic body radiotherapy (SBRT) and interventional pulmonology technologies, and provide a range of recommendations based on our expertise and experience. SUMMARY: Interventional pulmonology is an increasingly important approach for the management of pulmonary nodules. While more studies are needed to fully evaluate its long-term outcomes and benefits, the available evidence suggests that this technique can provide a minimally invasive and effective alternative for treating small malignancies in selected patients. We conducted a systematic literature review in PubMed, designed a framework to include the advances in surgery, SBRT, and interventional pulmonology for the treatment of pulmonary nodules, and provided a range of recommendations based on our expertise and experience. KEY MESSAGES: As such, alternative therapeutic options such as SBRT and ablation are becoming increasingly important and viable. With recent advancements in bronchoscopy techniques, ablation via bronchoscopy has emerged as a promising option for treating pulmonary nodules. This study reviewed the advances of interventional pulmonology in the treatment of peripheral lung cancer patients that are not surgical candidates. We also discussed the challenges and limitations associated with ablation, such as the risk of complications and the potential for incomplete nodule eradication. These advancements hold great promise for improving the efficacy and safety of interventional pulmonology in treating pulmonary nodules.

5.
Int Immunopharmacol ; 130: 111734, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38422768

RESUMO

Pulmonary fibrosis is an irreversible and progressive lung disease with limited treatments available. Selinexor (Sel), an orally available, small-molecule, selective inhibitor of XPO1, exhibits notable antitumor, anti-inflammatory and antiviral activities. However, its potential role in treating pulmonary fibrosis is unknown. C57BL/6J mice were used to establish a pulmonary fibrosis model by intratracheal administration of bleomycin (BLM). Subsequently, Sel was administered intraperitoneally. Our data demonstrated that Sel administration ameliorated BLM-induced pulmonary fibrosis by increasing mouse body weights; reducing H&E staining, Masson staining scores, and shadows in mouse lung computed tomography (CT) images, decreasing the total cell and neutrophil counts in the lung and bronchoalveolar lavage fluid (BALF); and decreasing the levels of TGF-ß1. We next confirmed that Sel reduced the deposition of extracellular matrix (ECM) components in the lungs of BLM-induced pulmonary fibrosis mice. We showed that collagen I, alpha-smooth muscle actin (α-SMA), and hydroxyproline levels and the mRNA levels of Col1a1, Eln, Fn1, Ctgf, and Fgf2 were reduced. Mechanistically, tandem mass tags (TMT)- based quantitative proteomics analysis revealed a significant increase in GBP5 in the lungs of BLM mice but a decrease in that of BLM + Sel mice; this phenomenon was confirmed by western blotting and RT-qPCR. NLRP3 inflammasome signaling was significantly enriched in both the BLM group and BLM + Sel group based on GO and KEGG analyses of differentially expressed proteins between the groups. Furthermore, Sel reduced the expression of NLRP3, cleaved caspase 1, and ASC in vivo and in vitro, and decreased the levels of IL-1ß, IL-18, and IFN-r in lung tissue and BALF. SiRNA-GBP5 inhibited NLRP3 signaling in vitro, and overexpression of GBP5 inhibited the protective effect of Sel against BLM-induced cellular injury. Taken together, our findings indicate that Sel ameliorates BLM-induced pulmonary fibrosis by targeting GBP5 via NLRP3 inflammasome signaling. Thus, the XPO1 inhibitor - Sel might be a potential therapeutic agent for pulmonary fibrosis.


Assuntos
Hidrazinas , Fibrose Pulmonar , Triazóis , Camundongos , Animais , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/tratamento farmacológico , Fibrose Pulmonar/metabolismo , Inflamassomos/metabolismo , Bleomicina/efeitos adversos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Camundongos Endogâmicos C57BL , Pulmão/patologia
6.
Asia Pac J Oncol Nurs ; 11(1): 100333, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38188370

RESUMO

Objective: This study aimed to assess the efficacy of a self-designed progressive resistance exercise training program for preventing the development of lower limb lymphedema. Methods: An open-label randomized controlled trial was conducted in patients who underwent radical surgery for cervical cancer treatment in our department between October 7, 2019, and October 7, 2021. The participants were randomly assigned to one of three groups: progressive resistance exercise training, graduated compression stocking, and control group. Results: A total of 267 patients were enrolled (89 in each group). The incidence of lower limb lymphedema was 9.0% (n = 8) in the progressive resistance exercise training group, 28.1% (n = 25) in the graduated compression stocking group, and 42.7% (n = 38) in the control group. Over the 2-year follow-up period, the risk of lower limb lymphedema was significantly lower in the progressive resistance exercise training group than in the control group, with a hazard ratio (HR) (95% confidence interval [CI]) of 0.156 (0.073-0.335). The study was underpowered to demonstrate a statistically significant reduction in risk in the graduated compression stocking group, with an HR (95% CI) of 0.624 (0.376-1.033). Conclusions: Progressive resistance exercise training is an effective strategy for preventing lower limb lymphedema after pelvic lymphadenectomy for cervical cancer. It imposes no additional economic burden and can be performed conveniently without the need for dedicated exercise facilities. This makes it particularly accessible to patients in developing countries, allowing them to exercise at their convenience. Trial registration: ChiCTR1800014905.

7.
World J Clin Oncol ; 15(1): 45-61, 2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38292659

RESUMO

BACKGROUND: Heat shock protein A4 (HSPA4) belongs to molecular chaperone protein family which plays important roles within variable cellular activities, including cancer initiation and progression. However, the prognostic and immunological significance of HSPA4 in lung adenocarcinoma (LUAD) has not been revealed yet. AIM: To explore the prognostic and immunological roles of HSPA4 to identify a novel prognostic biomarker and therapeutic target for LUAD. METHODS: We assessed the prognostic and immunological significance of HSPA4 in LUAD using data from The Cancer Genome Atlas database. The association between HSPA4 expression and clinical-pathological features was assessed through Kruskal-Wallis and Wilcoxon signed-rank test. Univariate/multivariate Cox regression analyses and Kaplan-Meier curves were employed to evaluate prognostic factors, including HSPA4, in LUAD. Gene set enrichment analysis (GSEA) was conducted to identify the key signaling pathways associated with HSPA4. The correlation between HSPA4 expression and cancer immune infiltration was evaluated using single-sample gene set enrichment analysis (ssGSEA). RESULTS: Overexpressing HSPA4 was significantly related to advanced pathologic TNM stage, advanced pathologic stage, progression disease status of primary therapy outcome and female subgroups with LUAD. In addition, increased HSPA4 expression was found to be related to worse disease-specific survival and overall survival. GSEA analysis indicated a significant correlation between HSPA4 and cell cycle regulation and immune response, particularly through diminishing the function of cytotoxicity cells and CD8 T cells. The ssGSEA algorithm showed a positive correlation between HSPA4 expression and infiltrating levels of Th2 cells, while a negative correlation was observed with cytotoxic cell infiltration levels. CONCLUSION: Our findings indicate HSPA4 is related to prognosis and immune cell infiltrates and may act as a novel prognostic biomarker and therapeutic target for LUAD.

8.
Front Med (Lausanne) ; 10: 1298778, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38076270

RESUMO

Introduction: It is necessary to explore the evidence-based practice of perioperative management of elderly patients undergoing ambulatory surgery, to optimize the clinical workflow and improve the quality of nursing care. Methods: Based on the best evidence obtained from the previous study, the perioperative management model and examination index of elderly patients undergoing day surgery were established, and the evidence of best practice was obtained by using the evidence-based methodology. Then, we integrated evidence into clinical practice and improved the process. We made a comparative analysis of the effect before and after the implementation of the evidence. Results: This study summarized 26 pieces of evidence of perioperative management of elderly patients undergoing day surgery and transformed the evidence into 7 items and 11 items of examination index. After the application of the best evidence, knowledge, belief, and practice of perioperative management of nurses for elderly patients in the day operation ward reached 100%, and the rate of reaching the standard of most indicators increased after the application of evidence. The length of waiting for admission and waiting for operation and returning to the ward to discharge of elderly patients decreased significantly, and the difference was statistically significant (All p < 0.05). Conclusion: Evidence-based perioperative management of elderly patients undergoing day surgery improves the nursing practice of clinical nurses and shortens the waiting time and hospitalization time of elderly patients undergoing day surgery, which should be promoted in clinical nursing care.

9.
Front Med (Lausanne) ; 10: 1209747, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38089873

RESUMO

Introduction: Tumor-associated autoantibodies have been revealed as promising biomarkers for the early detection of lung cancer. This study was designed to develop an autoantibody panel for early detection of lung cancer in the Chinese population. Methods: Recruited prospectively in three clinical centers, the subjects (n = 991) who had a definite diagnosis during follow-up were included in the development of the autoantibody panel. The levels of 14 autoantibody candidates in plasma were detected. Results: A panel of nine autoantibody markers (named as CN9), namely, P53, SOX2, SSX1, HuD, NY-ESO-1, CAGE, MAGE-A4, P62, and CK20, was preferably selected from 14 candidates. The overall specificity, sensitivity, and AUC were 90.5%, 40.8%, and 0.64, respectively. The CN9 panel demonstrated a reasonable detection rate in lung cancer patients at all stages, histological types, sizes of lesions, and risk levels. Its estimated overall accuracy is 85.5% and 90%, with PPV at 0.32 and 0.04, and NPV at 0.93 and 0.99 in the scenario of pulmonary nodules' characterizing and lung cancer screening, respectively. Two risk models were developed within the subgroups of malignant and benign pulmonary nodules in this study. By adding the CN9 result to the Mayo model indicators, it achieved a sensitivity of 41.3% and an AUC of 0.74 at a specificity of 91.3%. By adding the CN9 result to the Brock model indicators, it achieved a sensitivity of 47.7% and an AUC of 0.78 at a specificity of 91.3%. Both were improved compared with either the standalone Mayo or Brock model. Discussion: This multi-center prospective study indicates a panel of nine autoantibody markers that can help in the detection of lung cancer and the classification of pulmonary nodules in the Chinese population.

10.
Plants (Basel) ; 12(23)2023 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-38068606

RESUMO

Owing to its high ornamental, medicinal and horticultural values, herbaceous peony (Paeonia lactiflora Pall.) has been widely used as a landscaping and economical plant around the world. However, the lack of an efficient and stable regeneration system in P. lactiflora restricts its rapid propagation and large-scale production. By testing the key factors affecting callus formation, proliferation, adventitious bud induction and rooting, here, we developed an in vitro system for callus induction and regeneration in P. lactiflora. Our results show that callus formation was affected by explant types, culture environment, basal medium and plant growth regulators. Using cotyledons as explants, we established good conditions for P. lactiflora callus induction and callus proliferation. We effectively obtained adventitious buds differentiated from callus in Murashige and Skoog (MS) medium containing kinetin (KT) and thidiazuron (TDZ). Adventitious bud growth can be further promoted by adding gibberellin 3 (GA3), 1-naphthaleneacetic acid (NAA) and 6-benzyleaminopurine (6-BA) into the MS medium. A high percentage of rooting can be achieved by adding indolebutyric acid (IBA) and activated carbon (AC) to ½ MS medium. Overall, our system promotes callus induction and adventitious bud regeneration for P. lactiflora through improved culture conditions and plant growth regulators in the culture media, and lays a foundation for subsequent genetic engineering research.

11.
Cell Commun Signal ; 21(1): 325, 2023 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-37957625

RESUMO

BACKGROUND: Mechanism underlying the malignant progression of precancer to early-stage lung adenocarcinoma (LUAD) as well as their indolence nature remains elusive. METHODS: Single-cell RNA sequencing (scRNA) with simultaneous T cell receptor (TCR) sequencing on 5 normal lung tissues, 3 precancerous and 4 early-stage LUAD manifested as pulmonary ground-glass nodules (GGNs) were performed. RESULTS: Through this integrated analysis, we have delineated five key modules that drive the malignant progression of early-stage LUAD in a disease stage-dependent manner. These modules are related to cell proliferation and metabolism, immune response, mitochondria, cilia, and cell adhesion. We also find that the tumor micro-environment (TME) of early-stage LUAD manifested as GGN are featured with regulatory T (Tregs) cells accumulation with three possible origins, and loss-functional state (decreased clonal expansion and cytotoxicity) of CD8 + T cells. Instead of exhaustion, the CD8 + T cells are featured with a shift to memory phenotype, which is significantly different from the late stage LUAD. Furthermore, we have identified monocyte-derived macrophages that undergo a lipid-phenotype transition and may contribute to the suppressive TME. Intense interaction between stromal cells, myeloid cells including lipid associated macrophages and LAMP3 + DCs, and lymphocytes were also characterized. CONCLUSIONS: Our work provides new insight into the molecular and cellular mechanism underlying malignant progression of LUAD manifested as GGN, and pave way for novel immunotherapies for GGN. Video Abstract.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , RNA Citoplasmático Pequeno , Humanos , Lipídeos , Análise de Célula Única , Microambiente Tumoral
12.
Adv Colloid Interface Sci ; 321: 103007, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37812992

RESUMO

It is well known that metal-organic framework (MOF) nanostructures have unique characteristics such as high porosity, large surface areas and adjustable functionalities, so they are ideal candidates for developing drug delivery systems (DDSs) as well as theranostic platforms in cancer treatment. Despite the large number of MOF nanostructures that have been discovered, conventional MOF-derived nanosystems only have a single biofunctional MOF source with poor colloidal stability. Accordingly, developing core-shell MOF nanostructures with good colloidal stability is a useful method for generating efficient drug delivery, multimodal imaging and synergistic therapeutic systems. The preparation of core-shell MOF nanostructures has been done with a variety of materials, but inorganic nanoparticles (NPs) are highly effective for drug delivery and imaging-guided tumor treatment. Herein, we aimed to overview the synthesis of core-shell inorganic NP@MOF nanostructures followed by the application of core-shell MOFs derived from magnetic, quantum dots (QDs), gold (Au), and gadolinium (Gd) NPs in drug delivery and imaging-guided tumor treatment. Afterward, we surveyed different factors affecting prolonged drug delivery and cancer therapy, cellular uptake, biocompatibility, biodegradability, and enhanced permeation and retention (EPR) effect of core-shell MOFs. Last but not least, we discussed the challenges and the prospects of the field. We envision this article may hold great promise in providing valuable insights regarding the application of hybrid nanostructures as promising and potential candidates for multimodal imaging-guided combination cancer therapy.


Assuntos
Estruturas Metalorgânicas , Nanoestruturas , Neoplasias , Humanos , Estruturas Metalorgânicas/química , Sistemas de Liberação de Medicamentos , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Imagem Multimodal
13.
Heliyon ; 9(9): e19611, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37809439

RESUMO

We reported a case of a 60-year-old male with fever, cough, expectoration, and chest distress after right lung transplanted. Blood examination showed elevated C-reaction protein (CRP), white blood cell (WBC), and ammonia. Computed tomography (CT) revealed patchy high-density shadows and few pleural effusions in the transplanted lung. Bronchoscopy illustrated anastomotic fistula, and pseudomembrane and mucus plugs around the right main bronchial anastomosis. Carbapenem-resistant Klebsiella pneumoniae, Ureaplasma urealyticum, and Aspergillus flavus was successively detected by metagenomic next-generation sequencing (mNGS). Targeted anti-microbial agents were administered and patient was successfully discharged. Unfortunately, a year later, patient died of respiratory failure due to recurrent pulmonary infections.

14.
Asia Pac J Oncol Nurs ; 10(9): 100268, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37661960

RESUMO

Objective: This study aims to develop and test the self-management instrument for breast cancer patients undergoing adjuvant therapy (SMAT-B). Methods: After a qualitative interview with 29 patients and two rounds of Delphi expert consultation with 15 experts, 49 items were initially generated. Before item reduction, another structured interview was conducted for content validity. Item analysis and exploratory factor analysis (n â€‹= â€‹377) were used for item reduction. After that, internal consistency, split-half reliability, test-retest reliability (n â€‹= â€‹30), measurement error, construct validity, and structural validity (n â€‹= â€‹342) were preliminarily evaluated using the COnsesus-based Standards for the selection of health Measurements INstruments guidelines. Results: The final version of SMAT-B includes 7 dimensions and 31 items after item reduction. The testing results suggested that SMAT-B had good internal consistency (Total Cronbach's α â€‹= â€‹0.952), good split-half reliability (Spearman-Brown coefficient â€‹= â€‹0.904), good stability (Total intraclass correlation coefficient = â€‹0.797), acceptable measurement error (SEM â€‹= â€‹5.28), and acceptable construct validity (Standardized root mean square residual â€‹= â€‹0.055). The hypotheses of construct validity were all verified to a certain extent (r â€‹> â€‹0.20, P â€‹< â€‹0.01). Conclusions: The 31-item SMAT-B, developed in interviews with patients and consultation with experts, demonstrated good psychometric properties and can be recommended for researchers and clinicians for further validity testing and evaluation of the self-management ability of breast cancer patients. Trial registration: ChiCTR2100052868.

15.
Transl Lung Cancer Res ; 12(8): 1766-1781, 2023 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-37691861

RESUMO

Background: Lung cancer has the highest prevalence and mortality of all cancers, and lung adenocarcinoma (LUAD) occupies the largest proportion of lung cancers. Herein, this study is aimed at constructing a ferroptosis-related prognostic signature for LUAD and conducting functional analysis based on the signature, highlighting the importance of ferroptosis in LUAD. Methods: We employed RNA-sequencing (RNA-seq) and clinical data from The Cancer Genome Atlas (TCGA) database. Univariate Cox regression, Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis were conducted to build the ferroptosis-related genes (FRGs) prognostic signature. The efficacy of this FRG signature was further analyzed with Kaplan-Meier (KM) plot, multivariate Cox regression, and the receiver operating characteristic (ROC) curves. Enrichment analysis was used to evaluate key pathways. The expression of immunomodulators, immune infiltration status, and drug sensitivity correlation were explored to predict the response to various therapies. The expression of FRGs was validated in LUAD samples with western blot (WB) and immunohistochemistry (IHC) staining. Cell viability assay and lipid peroxidation detection were measured after small interfering RNA (siRNA) knockdown of two FRGs in lung cancer cell lines. Results: A seven-gene signature was constructed and used to divide LUAD patients into high- and low-risk groups. High-risk patients were notably related to shorter overall survival (OS), and multivariate Cox regression demonstrated that our signature was an independent predictor of OS. ROC curve analysis presented a maximum area under the curve (AUC) value of 0.740 for the experimental cohort and 0.705 for the validation cohort. The low-risk group showed higher levels of plasma cell infiltration and higher expression of programmed cell death protein 1 (PDCD1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA4). Ferroptosis inducers such as talazoparib or cisplatin had lower IC50 values in the high-risk group, while navitoclax (BCL-2 gene family inhibition and apoptosis inducer) had higher IC50 values in the high-risk group. Additionally, peroxiredoxin-6 (PRDX6) and acyl-CoA synthetase long chain family member 3 (ACSL3) were upregulated in LUAD tissues. Lipid peroxide assay showed that silencing PRDX6 or ACSL3 promoted lipid peroxidation and ferroptosis in lung cancer cells. Conclusions: Our novel ferroptosis-related signature shows potential clinical and functional importance in LUAD patients, and further research on ferroptosis as a therapeutic target in LUAD is warranted.

19.
J Hazard Mater ; 454: 131464, 2023 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-37104953

RESUMO

Carbon disulfide (CS2) exposure has been associated with lung function reduction in occupational population. However, evidence on the general population with relatively low CS2 exposure is lacking and the mechanism involved remains largely unknown. Urinary CS2 metabolite (2-mercaptothiazolidine-4-carboxylic acid, TTCA) and lung function were determined in the urban adults from the Wuhan-Zhuhai cohort at baseline in 2011-2012 and were repeated every 3 years. Cross-sectional and longitudinal associations between TTCA and lung function were estimated using linear mixed models. Inflammation and oxidative damage biomarkers in blood/urine were measured to evaluate their potential mediating roles involved. Cross-sectionally, participants in the highest quartile of TTCA level showed a 0.64% reduction in FEV1/FVC and a -308.22 mL/s reduction in PEF, compared to those in the lowest quartile. Longitudinally, participants with consistently high TTCA level had annually -90.27 mL/s decline in PEF, compared to those with consistently low TTCA level. Mediation analysis revealed that plasma protein carbonyl mediated 49.89% and 22.10% of TTCA-associated FEV1/FVC and PEF reductions, respectively. Conclusively, there was a cross-sectional and longitudinal association between CS2 exposure and lung function reduction in the general urban adults, and protein carbonylation (oxidative protein damage) partly mediated lung function reduction from CS2 exposure.


Assuntos
Dissulfeto de Carbono , Exposição Ocupacional , Adulto , Humanos , Dissulfeto de Carbono/toxicidade , Dissulfeto de Carbono/metabolismo , Estudos Transversais , Estresse Oxidativo , Pulmão/metabolismo , Exposição Ocupacional/análise
20.
Int J Biol Macromol ; 240: 124441, 2023 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-37060978

RESUMO

In the biological systems, exposure to nanoparticles (NPs) can cause complicated interactions with proteins, the formation of protein corona and structural changes to proteins. These changes depend not only on NP physicochemical properties, but also on the intrinsic stability of protein molecules. Although, the formation of protein corona on the surface of NPs and the underlying mechanisms have been fully explored in various studies, no comprehensive review has discussed the direct biochemical and biophysical interactions between NPs and blood proteins, particularly transferrin. In this review, we first discussed the interaction of NPs with proteins to comprehend the effects of physicochemical properties of NPs on protein structure. We then overviewed the transferrin structure and its direct interaction with NPs to explore transferrin stability and its iron ion (Fe3+) release behavior. Afterwards, we surveyed the various biological functions of transferrin, such as Fe3+ binding, receptor binding, antibacterial activity, growth, differentiation, and coagulation, followed by the application of transferrin-modified NPs in the development of drug delivery systems for cancer therapy. We believe that this study can provide useful insight into the design and development of bioconjugates containing NP-transferrin for potential biomedical applications.


Assuntos
Nanopartículas , Coroa de Proteína , Transferrina/química , Coroa de Proteína/química , Nanopartículas/química , Ferro/metabolismo , Ligação Proteica
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