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1.
Health Sci Rep ; 7(5): e2114, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38736477

RESUMO

Background and Aims: Immune checkpoint inhibitors (ICIs) across multiple treatment lines have not yet been evaluated comprehensively. The purpose of this research was to investigate whether or not continuous cross-line ICIs therapy is effective in treating non-small cell lung cancer (NSCLC). Methods: We conducted a retrospective investigation into the medical histories of 47 patients diagnosed with advanced NSCLC and treated with ICIs at the Peking University First Hospital between January 2018 and June 2022. Results: Due to the progression of their disease, 14 patients were given the same ICIs, 5 patients were given different ICIs, and 6 patients discontinued taking ICIs altogether. The objective response rates were 7.140% in the ICIs cross-line treatment group, 0% in the replacement of ICIs treatment group, and 0% in the discontinuation of ICIs treatment group. The disease control rates were 64.260% in the ICIs cross-line treatment group, 60% in the replacement of ICIs treatment group, and 0% in the discontinuation of ICIs treatment group. The average overall survival durations of the three groups were 24.020 (95% confidence interval [CI]: 17.061-30.979), 31.643 (95% CI: 23.513-39.774), and 7.997 (95% CI: 3.746-12.247) months, respectively (p = 0.003). The median second progression-free survival (PFS2) durations of the three groups were 4.570 (95% CI: 3.276-5.864), 3.530 (95% CI: 0.674-6.386), and 1.570 (95% CI: 0-4.091) months, respectively (p = 0.091). Conclusions: Cross-line ICIs cannot improve the prognosis and PFS2 of patients with NSCLC, but compared to discontinuing ICIs, OS may be prolonged. A few patients may benefit from prolonged ICIs therapy.

2.
China CDC Wkly ; 6(15): 324-331, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38736991

RESUMO

Introduction: In the first half of 2023, a global shift was observed towards the predominance of XBB variants. China faced a significant epidemic between late 2022 and early 2023 due to Omicron subvariants BA.5.2 and BF.7. This study aims to depict the evolving variant distribution among provincial-level administrative divisions (PLADs) in China and explore the factors driving the predominance of XBB replacement. Methods: Sequences from local and imported coronavirus disease 2019 (COVID-19) cases recorded between January 1 and June 30, 2023, were included. The study analyzed the changing distribution of viral variants and assessed how the prior dominance of specific variants, XBB subvariants, and imported cases influenced the prevalence of the XBB replacement variant. Results: A total of 56,486 sequences were obtained from local cases, and 8,669 sequences were from imported cases. Starting in April, there was a shift in the prevalence of XBB from imported to local cases, with varying dominance among PLADs. In PLADs previously high in BF.7, the rise of XBB was delayed. A positive correlation was found between XBB proportions in imported cases from January to March and local cases in April. The distribution pattern of XBB subvariants differed between local and imported cases within the same PLAD. No significant differences were noted in the replacement rates of XBB subvariants. Conclusions: The timing of XBB dominance differed among various PLADs in China in the first half of 2023, correlating closely with the prevalence of XBB variants among imported cases.

3.
Heliyon ; 10(9): e30226, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38742062

RESUMO

Root-knot nematodes (RKNs) pose a serious threat to crop production. Flooding soil with biogas slurry, combined with soil heating before crop planting, has the potential for RKN disease suppression. However, the actual effect of this method has not been verified under field conditions. Here, we present the results of a two-year field experiment in a greenhouse demonstrating the control effect on RKN disease and plant growth using this method, as well as its influence on the soil nematode community. Four treatments were set: untreated control (CK), local control method for RKN (CC), soil flooded with 70 % biogas slurry (BS70), and soil flooded with undiluted biogas slurry (BS100). In the first year, all three RKN control treatments significantly reduced the root-knot index (p < 0.05). In the next year, only BS70 and BS100 still presented significantly suppressed effects (p < 0.05), and it was more obvious under BS70 with a relative control effect of 74.6 %. In the first year, BS70 and BS100 significantly inhibited the plant height of watermelon (p < 0.05). In the next year, however, all three RKN control treatments promoted the growth of watermelon, and their stem diameter was significantly greater than that of CK. The application of biogas slurry (BS70 and BS100) significantly increased nematode richness and the Shannon index in the second year (p < 0.05). However, the structure index showed no significant difference among treatments (p > 0.05), indicating that biogas slurry application did not increase the soil food web complex. Principal component analysis showed that the application of biogas slurry changed the nematode community, especially under BS70, which presented a more lasting influence. The high-level input of biogas slurry also caused soil NH4+-N and heavy-metal and arsenic accumulation in the first year, but these soil-pollution risks disappeared in the second year.

4.
J Phys Chem Lett ; 15(19): 5088-5095, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38708949

RESUMO

The present work introduces a novel catalytic strategy to promote the nitrogen reduction reaction (NRR) by employing a cooperative Cu-based single-atom alloy (SAA) and oriented external electric fields (OEEFs) as catalysts. The field strength (F)-dependent reaction pathways are investigated by means of first-principles calculations. Different dipole-induced responses of intermediates to electric fields break the original scaling relationships and effectively tune not only the activity but also the product selectivity of the NRR. When the most active Os1Cu SAA is taken as an example, in the absence of an OEEF, the overpotential (η) of the NRR is 0.62 V, which is even larger than that of the competitive hydrogen evolution reaction (HER). A negative field not only reduces η but switches the preference to the NRR over the HER. In particular, η at F = -1.14 V/Šreaches the bottom of 0.18 V, which is 70% lower than that in the field-free state.

5.
J Pharm Biomed Anal ; 245: 116185, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38723556

RESUMO

Human epidermal growth factor receptor 2 (HER2) is a key player in the pathogenesis and progression of breast cancer and is currently a primary target for breast cancer immunotherapy. Bioactivity determination is necessary to guarantee the safety and efficacy of therapeutic antibodies targeting HER2. Nevertheless, currently available bioassays for measuring the bioactivity of anti-HER2 mAbs are either not representative or have high variability. Here, we established a reliable reporter gene assay (RGA) based on T47D-SRE-Luc cell line that expresses endogenous HER2 and luciferase controlled by serum response element (SRE) to measure the bioactivity of anti-HER2 antibodies. Neuregulin-1 (NRG-1) can lead to the heterodimerization of HER2 on the cell membrane and induce the expression of downstream SRE-controlled luciferase, while pertuzumab can dose-dependently reverse the reaction, resulting in a good dose-response curve reflecting the activity of the antibody. After optimizing the relevant assay parameters, the established RGA was fully validated based on ICH-Q2 (R1), which demonstrated that the method had excellent specificity, accuracy, precision, linearity, and stability. In summary, this robust and innovative bioactivity determination assay can be applied in the development and screening, release control, biosimilar assessment and stability studies of anti-HER2 mAbs.


Assuntos
Anticorpos Monoclonais Humanizados , Bioensaio , Genes Reporter , Luciferases , Neuregulina-1 , Receptor ErbB-2 , Receptor ErbB-2/genética , Receptor ErbB-2/imunologia , Receptor ErbB-2/antagonistas & inibidores , Humanos , Linhagem Celular Tumoral , Anticorpos Monoclonais Humanizados/farmacologia , Bioensaio/métodos , Luciferases/genética , Neuregulina-1/genética , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/imunologia , Neoplasias da Mama/genética , Feminino , Antineoplásicos Imunológicos/farmacologia , Reprodutibilidade dos Testes , Elementos de Resposta
6.
J Med Virol ; 96(5): e29664, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38727137

RESUMO

The causative agent of coronavirus disease 2019 (COVID-19), known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread accumulatively to 240 countries and continues to evolve. To gain a comprehensive understanding of the epidemiological characteristics of imported variants in China and their correlation with global circulating variants, genomic surveillance data from 11 139 imported COVID-19 cases submitted by Chinese provincial CDC laboratories between 2021 and 2022 were analyzed. Consensus sequences underwent rigorous quality checks, followed by amino acid mutations analysis using Nextclade. Sequences with satisfactory quality control status were classified according to the Pango nomenclature. The results showed that the dominant variants in imported cases reflected the global epidemic trend. An increase in the number of imported SARS-CoV-2 lineages monitored in China in the second half of 2022, and the circulating Omicron subvariants changed from the ancestral lineages of BA.5 and BA.2 into the lineages containing key amino acid mutations of spike protein. There was significant variation in the detection of Omicron subvariants among continents (χ2 = 321.968, p < 0.001) in the second half of 2022, with four lineages (BA.2.3.7, BA.2.2, BA.5.2.7, and XBB.1.2) identified through imported surveillance mainly prevalent respectively in Taiwan, China, Hong Kong SAR, China, Russian Federation, and Singapore. These findings revealed the alterations in circulating imported variants from 2021 to 2022 in China, reflecting the higher diversity of lineages in the second half of 2022, and revealed the predominant lineages of countries or regions that are in close contacts to China, providing new insights into the global prevalence of SARS-CoV-2.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , China/epidemiologia , COVID-19/epidemiologia , COVID-19/virologia , SARS-CoV-2/genética , SARS-CoV-2/classificação , Prevalência , Glicoproteína da Espícula de Coronavírus/genética , Filogenia , Mutação , Genoma Viral/genética , Variação Genética
7.
Front Pediatr ; 12: 1305456, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38742242

RESUMO

Objective: The aim of this study was to identify the risk factors for postoperative adverse events in children with duplex kidney undergoing upper pole heminephrectomy. Methods: We collected clinical data from pediatric patients with duplex kidney who underwent upper pole heminephrectomy. Based on the presence or absence of postoperative adverse events, the patients were divided into two groups: an adverse events group (n = 16) and a non- adverse events group (n = 37), using multivariate logistic regression analysis to screen for independent risk factors for postoperative adverse events. Results: Through univariate and multivariate analysis, we found that the presence of upper renal ureterocele (P = 0.042, OR = 7.116, 95% CI 1.073-47.172), as well as the presence of accessory renal artery type (P = 0.016, OR = 10.639, 95% CI 1.551-72.978) and other types (P = 0.039, OR = 3.644, 95% CI 0.351-37.836) as the upper kidney's blood supply artery increase the risk of postoperative adverse events, with these differences being statistically significant. Conclusions: In pediatric patients with duplex kidney undergoing upper pole heminephrectomy, the presence of upper renal ureterocele and the presence of accessory renal artery type and other types as the upper kidney's blood supply artery are independent risk factors for postoperative adverse events.

8.
J Occup Rehabil ; 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38743130

RESUMO

PURPOSE: There is a wide range of individual and work environment factors that influence work ability among workers with pain and stress-related ill-health. The multiple interactions and overlap between these factors are insufficiently understood, and a network approach could mitigate limitations of previous research. This pilot study aimed to explore interactions between individual characteristics and psychosocial work environment and potential links to long-term work ability. METHODS: Prospective data from a prevention project was used. Individuals (N = 147) with pain and/or stress-related ill-health (95% women) at public sector workplaces filled out baseline questionnaires about a collection of individual and work environment factors, which were used for constructing undirected networks. The model was run in three subsamples of workplaces. Finally, a separate model was established with work ability at 6-month follow-up as outcome variable. A shortest pathway analysis was calculated to identify mediators of work ability. RESULTS: Symptom catastrophizing and perceived stress were the most influential factors in all network models. Symptom catastrophizing and pain-disability risk were found to mediate the relation between perceived stress and long-term work ability. Further, demand-control-support factors were interrelated, and patterns of interaction differed between different types of workplaces. CONCLUSION: The findings support the importance of individual factors, specifically symptom catastrophizing in an individual's coping with pain or stress-problems and its influence on long-term work ability. Catastrophizing might play a role in stress-related disorders which should be further investigated. Individual and work environment factors interact and vary across context, which needs to be taken into consideration to prevent pain and stress-related ill-health at work.

9.
Open Med (Wars) ; 19(1): 20240946, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38584841

RESUMO

Esophageal squamous cell carcinoma (ESCC), a highly aggressive subtype of esophageal cancer, is characterized by late-stage diagnosis and limited treatment options. Recent advancements in transcriptome sequencing technologies have illuminated the molecular intricacies of ESCC tumors, revealing metabolic reprogramming as a prominent feature. Specifically, the Warburg effect, marked by enhanced glycolysis, has emerged as a hallmark of cancer, offering potential therapeutic targets. In this study, we comprehensively analyzed bulk RNA-seq data from ESCC patients, uncovering elevated SRA1 expression in ESCC development and a poorer prognosis. Silencing of SRA1 led to a modulation of glycolysis-related products and a shift in PKM2 expression. Our findings shed light on the intricate molecular landscape of ESCC, highlighting SRA1 as a potential therapeutic target to disrupt glycolysis-dependent energy production. This metabolic reprogramming may hold the key to innovative treatment strategies for ESCC, ultimately improving patient outcomes.

11.
J Vis Exp ; (205)2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38619255

RESUMO

Facing a 40% mortality rate in candidemia patients, drug-resistant Candida and their petite mutants remain a major treatment challenge. Antimicrobial photodynamic therapy (aPDT) targets multiple fungal structures, unlike antibiotics/antifungals, potentially thwarting resistance. Traditional methods for inducing petite colonies rely on ethidium bromide or fluconazole, which can influence drug susceptibility and stress responses. This study investigated the application of green light (peak 520 nm) and rose bengal (RB) photosensitizer to combat a drug-resistant Candida glabrata isolate. The findings revealed that aPDT treatment significantly inhibited cell growth (≥99.9% reduction) and effectively induced petite colony formation, as evidenced by reduced size and loss of mitochondrial redox indicator staining. This study provides initial evidence that aPDT can induce petite colonies in a multidrug-resistant C. glabrata strain in vitro, offering a potentially transformative approach for combating resistant fungal infections.


Assuntos
Candida , Fotoquimioterapia , Humanos , Rosa Bengala/farmacologia , Candida glabrata , Fármacos Fotossensibilizantes/farmacologia
12.
Environ Sci Technol ; 58(20): 8709-8723, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38656828

RESUMO

Microplastics (MPs), plastic particles smaller than 5 mm, are now a growing environmental and public health issue, as they are detected pervasively in freshwater and marine environments, ingested by organisms, and then enter the human body. Industrial development drives this environmental burden caused by MP formation and human uptake by elevating plastic pollution levels and shaping the domestic dietary structure. We map the MP human uptake across 109 global countries on five continents from 1990 to 2018, focusing on the world's major coastlines that are affected by plastic pollution that affects the United Nations' Sustainable Development Goals (SDGs): SDG 6 (Clean Water and Sanitation), SDG 14 (Life Below Water), and SDG 15 (Life on Land). Amid rapid industrial growth, Indonesia tops the global per capita MP dietary intake at 15 g monthly. In Asian, African, and American countries, including China and the United States, airborne and dietary MP uptake increased over 6-fold from 1990 to 2018. Eradicating 90% of global aquatic plastic debris can help decrease MP uptake by more than 48% in Southeast Asian countries that peak MP uptake. To reduce MP uptake and potential public health risks, governments in developing and industrialized countries in Asia, Europe, Africa, and North and South America should incentivize the removal of free plastic debris from freshwater and saltwater environments through advanced water treatment and effective solid waste management practices.


Assuntos
Microplásticos , Plásticos , Humanos , Países em Desenvolvimento , Desenvolvimento Industrial
13.
Front Bioeng Biotechnol ; 12: 1352098, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38585708

RESUMO

The Chinese hamster ovarian (CHO) cells serve as a common choice in biopharmaceutical production, traditionally cultivated in stirred tank bioreactors (STRs). Nevertheless, the pursuit of improved protein quality and production output for commercial purposes demand exploration into new bioreactor types. In this context, inverted frustoconical shaking bioreactors (IFSB) present unique physical properties distinct from STRs. This study aims to compare the production processes of an antibody-based biotherapeutic in both bioreactor types, to enhance production flexibility. The findings indicate that, when compared to STRs, IFSB demonstrates the capability to produce an antibody-based biotherapeutic with either comparable or enhanced bioprocess performance and product quality. IFSB reduces shear damage to cells, enhances viable cell density (VCD), and improves cell state at a 5-L scale. Consequently, this leads to increased protein expression (3.70 g/L vs 2.56 g/L) and improved protein quality, as evidenced by a reduction in acidic variants from 27.0% to 21.5%. Scaling up the culture utilizing the Froude constant and superficial gas velocity ensures stable operation, effective mixing, and gas transfer. The IFSB maintains a high VCD and cell viability at both 50-L and 500-L scales. Product expression levels range from 3.0 to 3.6 g/L, accompanied by an improved acidic variants attribute of 20.6%-22.7%. The IFSB exhibits superior productivity and product quality, underscoring its potential for incorporation into the manufacturing process for antibody-based biotherapeutics. These results establish the foundation for IFSB to become a viable option in producing antibody-based biotherapeutics for clinical and manufacturing applications.

14.
Artigo em Inglês | MEDLINE | ID: mdl-38557898

RESUMO

Adoptive cell therapies involve infusing engineered immune cells into cancer patients to recognize and eliminate tumor cells. Adoptive cell therapy, as a form of living drug, has undergone explosive growth over the past decade. The recognition of tumor antigens by the T-cell receptor (TCR) is one of the natural mechanisms that the immune system used to eliminate tumor cells. TCR-T cell therapy, which involves introducing exogenous TCRs into patients' T cells, is a novel cell therapy strategy. TCR-T cell therapy can target the entire proteome of cancer cells. Engineering T cells with exogenous TCRs to help patients combat cancer has achieved success in clinical trials, particularly in treating solid tumors. In this review, we examine the progress of TCR-T cell therapy over the past five years. This includes the discovery of new tumor antigens, protein engineering techniques for TCR, reprogramming strategies for TCR-T cell therapy, clinical studies on TCR-T cell therapy, and the advancement of TCR-T cell therapy in China. We also propose several potential directions for the future development of TCR-T cell therapy.

15.
Sarcoidosis Vasc Diffuse Lung Dis ; 41(1): e2024008, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38567562

RESUMO

BACKGROUND AND AIM: Sarcoidosis is a granulomatous disease. Malignant tumors are accompanied rarely by granuloma reactions that mimic metastasis. METHODS: We present the case of a patient with possible advanced lung cancer with metastases to the mediastinal lymph nodes and bilateral ilia. RESULTS: Ilium biopsy revealed the presence of sarcoid-like reaction. Bronchoscopy and endobronchial ultrasound revealed an adenocarcinoma in the right upper lung lobe, with a negative mediastinal lymph node. The correct staging of lung cancer was achieved through pathological examination of the surgically removed lung tissues. Two years later, the lung cancer metastasized, and the patient underwent systemic treatment. CONCLUSIONS: Coexistent sarcoid-like reaction may mimic metastatic lung cancer. A multidisciplinary approach and sequential diagnostic biopsies can prevent unnecessary surgery or inadequate treatment by distinguishing between coexistent sarcoidosis and metastatic lung cancer.

16.
iScience ; 27(5): 109674, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38646169

RESUMO

Cancer-associated fibroblasts (CAFs) have been shown to play a key role in prostate cancer treatment resistance, but the role of CAFs in the initial course of enzalutamide therapy for prostate cancer remains unclear. Our research revealed that CAFs secrete CCL5, which promotes the upregulation of androgen receptor (AR) expression in prostate cancer cells, leading to resistance to enzalutamide therapy. Furthermore, CCL5 also enhances the expression of tumor programmed death-ligand 1 (PD-L1), resulting in immune escape. Mechanistically, CCL5 binds to the receptor CCR5 on prostate cancer cells and activates the AKT signaling pathway, leading to the upregulation of AR and PD-L1. The CCR5 antagonist maraviroc to inhibit the CAFs mediated CCL5 signaling pathway can effectively reduce the expression of AR and PD-L1, and improve the efficacy of enzalutamide. This study highlights a promising therapeutic approach targeting the CCL5-CCR5 signaling pathway to improve the effectiveness of enzalutamide.

17.
J Sci Food Agric ; 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38651728

RESUMO

BACKGROUND: The present study investigated the structure, functional and physicochemical properties of lotus seed protein (LSP) under different pH environments. The structures of LSP were characterized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, Fourier transform infrared spectroscopy (FTIR), zeta potential, particle size distributions, free sulfhydryl and rheological properties. The functional and physicochemical properties of LSP were characterized by color, foaming property, emulsification property, solubility, oil holding capacity, water holding capacity, differential scanning calorimetry analysis and surface hydrophobicity. RESULTS: LSP was mainly composed of eight subunits (18, 25, 31, 47, 51, 56, 65 and 151 kDa), in which the richest band was 25 kDa. FTIR results showed that LSP had high total contents of α-helix and ß-sheet (44.81-46.85%) in acidic environments. Meanwhile, there was more ß-structure and random structure in neutral and alkaline environments (pH 7.0 and 9.0). At pH 5.0, LSP had large particle size (1576.98 nm), high emulsion stability index (91.43 min), foaming stability (75.69%) and water holding capacity (2.21 g g-1), but low solubility (35.98%), free sulfhydryl content (1.95 µmol g-1) and surface hydrophobicity (780). DSC analysis showed the denaturation temperatures (82.23 °C) of LSP at pH 5.0 was higher than those (80.10, 80.52 and 71.82 °C) at pH 3.0, 7.0 and 9.0. The analysis of rheological properties showed that LSP gel had high stability and great strength in an alkaline environment. CONCLUSION: The findings of the present study are anticipated to serve as a valuable reference for the implementation of LSP in the food industry. © 2024 Society of Chemical Industry.

18.
Pestic Biochem Physiol ; 201: 105897, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38685223

RESUMO

Solid nanodispersion (SND) is an important variety of nanopesticides which have been extensively studied in recent years. However, the key influencing factors for bioactivity enhancement of nanopesticides remain unclear, which not only limits the exploration of relevant mechanisms, but also hinders the precise design and development of nanopesticides. In this study, we explored the potential of SND in enhancing the bioactivity of nanopesticides, specifically focusing on abamectin SND prepared using a self-emulsifying-carrier solidifying technique combined with parameter optimization. Our formulation, consisting of 8% abamectin, 1% antioxidant BHT (2,6-di-tert-butyl-4-methylphenol), 12% complex surfactants, and 79% sodium benzoate, significantly increased the pseudo-solubility of abamectin by at least 3300 times and reduced its particle size to a mere 15 nm, much smaller than traditional emulsion in water (EW) and water-dispersible granule (WDG) forms. This reduction in particle size and increase in surface activity resulted in improved foliar adhesion and retention, enabling a more efficient application without the need for organic solvents. The inclusion of antioxidants also enhanced photostability compared to EW, and overall stability tests confirmed SND's resilience under various storage conditions. Bioactivity tests demonstrated a marked increase in toxicity against diamondback moths (Plutella xylostella L.) with abamectin SND, which exhibited 3.7 and 7.6 times greater efficacy compared to EW and WDG, respectively. These findings underscore the critical role of small particle size, high surface activity, and strong antioxidant properties in improving the performance and bioactivity of abamectin SND, highlighting its significance in the design and development of high-efficiency, eco-friendly nanopesticides and contributing valuably to sustainable agricultural practices.


Assuntos
Ivermectina , Ivermectina/análogos & derivados , Ivermectina/farmacologia , Ivermectina/química , Animais , Inseticidas/farmacologia , Inseticidas/química , Tamanho da Partícula , Antioxidantes/farmacologia , Antioxidantes/química , Nanopartículas/química , Mariposas/efeitos dos fármacos , Tensoativos/farmacologia , Tensoativos/química , Larva/efeitos dos fármacos , Emulsões
19.
J Proteome Res ; 23(5): 1713-1724, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38648079

RESUMO

Non-small-cell lung cancer (NSCLC), a common malignant tumor, requires deeper pathogenesis investigation. Autophagy is an evolutionarily conserved lysosomal degradation process that is frequently blocked during cancer progression. It is an urgent need to determine the novel autophagy-associated regulators in NSCLC. Here, we found that pirin was upregulated in NSCLC, and its expression was positively correlated with poor prognosis. Overexpression of pirin inhibited autophagy and promoted NSCLC proliferation. We then performed data-independent acquisition-based quantitative proteomics to identify the differentially expressed proteins (DEPs) in pirin-overexpression (OE) or pirin-knockdown (KD) cells. Among the pirin-regulated DEPs, ornithine decarboxylase 1 (ODC1) was downregulated in pirin-KD cells while upregulated along with pirin overexpression. ODC1 depletion reversed the pirin-induced autophagy inhibition and pro-proliferation effect in A549 and H460 cells. Immunohistochemistry showed that ODC1 was highly expressed in NSCLC cancer tissues and positively related with pirin. Notably, NSCLC patients with pirinhigh/ODC1high had a higher risk in terms of overall survival. In summary, we identified pirin and ODC1 as a novel cluster of prognostic biomarkers for NSCLC and highlighted the potential oncogenic role of the pirin/ODC1/autophagy axis in this cancer type. Targeting this pathway represents a possible therapeutic approach to treat NSCLC.


Assuntos
Autofagia , Carcinoma Pulmonar de Células não Pequenas , Proliferação de Células , Progressão da Doença , Neoplasias Pulmonares , Ornitina Descarboxilase , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Humanos , Autofagia/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Proliferação de Células/genética , Ornitina Descarboxilase/metabolismo , Ornitina Descarboxilase/genética , Linhagem Celular Tumoral , Prognóstico , Regulação Neoplásica da Expressão Gênica , Células A549 , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Masculino , Feminino , Regulação para Cima
20.
ACS Appl Mater Interfaces ; 16(17): 22558-22570, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38637157

RESUMO

The development of nanopesticides provides new avenues for pesticide reduction and efficiency improvement. However, the size effect of nanopesticides remains unclear, and its underlying mechanisms of influence have become a major obstacle in the design and application of pesticide nanoformulations. In this research, the noncarrier-coated emamectin benzoate (EB) solid dispersions (Micro-EB and Nano-EB) were produced under a constant surfactant-to-active ingredient ratio by a self-emulsifying-carrier solidification technique. The particle size of Micro-EB was 162 times that of spherical Nano-EB. The small size and large specific surface area of Nano-EB facilitated the adsorption of surfactants on the surface of the particles, thereby improving its dispersibility, suspensibility, and stability. The pinning effect of nanoparticles significantly suppressed droplet retraction and rebounding. Moreover, Nano-EB exhibited a 25% higher retention of the active ingredient on cabbage leaves and a 70% higher washing resistance than Micro-EB, and both were significantly different. The improvement of abilities in wetting, spreading, and retention of Nano-EB on crop leaves contributed to the increase in foliar utilization, which further resulted in a 1.6-fold enhancement of bioactivity against target Spodoptera exigua compared to Micro-EB. Especially, Nano-EB did not exacerbate the safety risk to the nontarget organism zebrafish with no significant difference. This study elaborates the size effect on the effectiveness and safety of pesticide formulations and lays a theoretical foundation for the development and rational utilization of efficient and environmentally friendly nanopesticides.


Assuntos
Ivermectina , Ivermectina/análogos & derivados , Nanopartículas , Tamanho da Partícula , Spodoptera , Ivermectina/farmacologia , Ivermectina/química , Animais , Spodoptera/efeitos dos fármacos , Nanopartículas/química , Inseticidas/farmacologia , Inseticidas/química , Folhas de Planta/química , Folhas de Planta/metabolismo , Tensoativos/química , Tensoativos/farmacologia , Brassica/efeitos dos fármacos
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