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1.
Environ Sci Technol ; 58(16): 7066-7077, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38597811

RESUMO

Reactive oxygen species (ROS) are ubiquitous in the natural environment and play a pivotal role in biogeochemical processes. However, the spatiotemporal distribution and production mechanisms of ROS in riparian soil remain unknown. Herein, we performed uninterrupted monitoring to investigate the variation of ROS at different soil sites of the Weihe River riparian zone throughout the year. Fluorescence imaging and quantitative analysis clearly showed the production and spatiotemporal variation of ROS in riparian soils. The concentration of superoxide (O2•-) was 300% higher in summer and autumn compared to that in other seasons, while the highest concentrations of 539.7 and 20.12 µmol kg-1 were observed in winter for hydrogen peroxide (H2O2) and hydroxyl radicals (•OH), respectively. Spatially, ROS production in riparian soils gradually decreased along with the stream. The results of the structural equation and random forest model indicated that meteorological conditions and soil physicochemical properties were primary drivers mediating the seasonal and spatial variations in ROS production, respectively. The generated •OH significantly induced the abiotic mineralization of organic carbon, contributing to 17.5-26.4% of CO2 efflux. The obtained information highlighted riparian zones as pervasive yet previously underestimated hotspots for ROS production, which may have non-negligible implications for carbon turnover and other elemental cycles in riparian soils.


Assuntos
Carbono , Espécies Reativas de Oxigênio , Estações do Ano , Solo , Solo/química , Espécies Reativas de Oxigênio/metabolismo , Peróxido de Hidrogênio/metabolismo
2.
Ecotoxicol Environ Saf ; 277: 116374, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38677072

RESUMO

Farmland soil organisms frequently encounter pesticide mixtures presented in their living environment. However, the underlying toxic mechanisms employed by soil animals to cope with such combined pollution have yet to be explored. This investigation aimed to reveal the changes in cellular and mRNA levels under chlorpyrifos (CPF) and lambda-cyhalothrin (LCT) co-exposures in earthworms (Eisenia fetida). Results exhibited that the combination of CPF and LCT triggered an acute synergistic influence on the animals. Most exposures resulted in significant alterations in the activities of total superoxide dismutase (T-SOD), copper/zinc superoxide dismutase (Cu/Zn-SOD), caspase 3, and carboxylesterase (CarE) compared to the basal level. Moreover, when exposed to chemical mixtures, the transcription levels of four genes [heat shock protein 70 (hsp70), gst, sod, and calreticulin (crt)] also displayed more pronounced changes compared with their individual exposures. These changes in determined parameters indicated the occurrence of oxidative stress, cell death, detoxification dysfunction, and endoplasmic reticulum damage after co-exposure to CPF and LCT in E. fetida. The comprehensive examination of mixture toxicities of CPF and LCT at different endpoints would help to understand the overall toxicity they cause to soil invertebrates. The augmented deleterious effect of these pesticides in a mixture suggested that mixture toxicity assessment was necessary for the safety evaluation and application of pesticide mixtures.


Assuntos
Clorpirifos , Proteínas de Choque Térmico HSP70 , Nitrilas , Oligoquetos , Estresse Oxidativo , Piretrinas , Poluentes do Solo , Superóxido Dismutase , Animais , Oligoquetos/efeitos dos fármacos , Clorpirifos/toxicidade , Piretrinas/toxicidade , Nitrilas/toxicidade , Superóxido Dismutase/metabolismo , Poluentes do Solo/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Proteínas de Choque Térmico HSP70/genética , Proteínas de Choque Térmico HSP70/metabolismo , Carboxilesterase/metabolismo , Inseticidas/toxicidade , Caspase 3/metabolismo , Caspase 3/genética , Calreticulina/genética , Calreticulina/metabolismo , Glutationa Transferase/metabolismo , Glutationa Transferase/genética
3.
J Craniofac Surg ; 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38861329

RESUMO

Reconstructive surgery plays a crucial role in addressing congenital defects, posttraumatic deformities, and related conditions, providing transformative solutions for patients. Its primary goal is to restore or enhance damaged tissue structures, improving both functionality and appearance, and empowering individuals to lead fulfilling lives. Take, for example, a female patient who experienced a nasal infection after a cat bite. Despite initial treatment, she developed severe scar contractures and excessive scar tissue within her nostrils, significantly impacting her quality of life. Seeking assistance, she consulted the authors' plastic and reconstructive surgery team. By utilizing various flap techniques, the authors embarked on the intricate journey of reconstructing her nasal framework, ultimately restoring both form and function.

4.
Molecules ; 29(5)2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38474673

RESUMO

1,3,6-Trigalloylglucose is a natural compound that can be extracted from the aqueous extracts of ripe fruit of Terminalia chebula Retz, commonly known as "Haritaki". The potential anti-Helicobacter pylori (HP) activity of this compound has not been extensively studied or confirmed in scientific research. This compound was isolated using a semi-preparative liquid chromatography (LC) system and identified through Ultra-high-performance liquid chromatography-MS/MS (UPLC-MS/MS) and Nuclear Magnetic Resonance (NMR). Its role was evaluated using Minimum inhibitory concentration (MIC) assay and minimum bactericidal concentration (MBC) assay, scanning electron microscope (SEM), inhibiting kinetics curves, urea fast test, Cell Counting Kit-8 (CCK-8) assay, Western blot, and Griess Reagent System. Results showed that this compound effectively inhibits the growth of HP strain ATCC 700392, damages the HP structure, and suppresses the Cytotoxin-associated gene A (Cag A) protein, a crucial factor in HP infection. Importantly, it exhibits selective antimicrobial activity without impacting normal epithelial cells GES-1. In vitro studies have revealed that 1,3,6-Trigalloylglucose acts as an anti-adhesive agent, disrupting the adhesion of HP to host cells, a critical step in HP infection. These findings underscore the potential of 1,3,6-Trigalloylglucose as a targeted therapeutic agent against HP infections.


Assuntos
Helicobacter pylori , Terminalia , Extratos Vegetais/química , Terminalia/química , Cromatografia Líquida , Espectrometria de Massas em Tandem , Água
5.
Colloids Surf B Biointerfaces ; 234: 113757, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38241895

RESUMO

Biocompatible carbon quantum dots (CQDs) containing anti-osteosarcoma elements are intriguing therapeutics promising for bioimaging and tumor therapy. However, how the anti-osteosarcoma element doped in the structure of such CQDs triggers tumor inhibition remains unclear. Here, selenium-doped CQDs (Se-CQDs) are developed via a one-step hydrothermal route using discarded orange peel as a carbon source and structurally characterized by various physicochemical techniques. The biocompatibility and anti-osteosarcoma efficacy are deeply evaluated using animal and cell models. The resulting spherical Se-CQDs, with a 3-7 nm diameter, possess green-yellow tunable luminescence and excellent biocompatibility. Cell experiments show that Se-CQDs can be up-taken by osteosarcoma U2OS cells and activate the mitochondrial apoptosis pathway triggered by increased reactive oxygen species. They can arrest the cell cycle at the G2/S phase and promote cellular apoptosis with reduced invasion and migration. Molecularly, Se-CQDs can down-regulate the expression of DNMT1 while up-regulating the expression of PTEN due to the decreased promoter methylation. Notably, Se-incorporated CQDs are more effective in inhibiting the proliferation, migration, and invasion of osteosarcoma than Se-free CQDs. It is feasible to use Se-CQDs as candidates for the potential application of early monitoring and treatment of osteosarcoma.


Assuntos
Neoplasias Ósseas , Osteossarcoma , Pontos Quânticos , Animais , Pontos Quânticos/química , Carbono/química , Apoptose/genética , Osteossarcoma/patologia , Metilação , Neoplasias Ósseas/genética
6.
J Cancer Res Ther ; 20(2): 578-583, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38687927

RESUMO

OBJECTIVE: This study aimed to evaluate the efficacy and safety of sequential treatment of continuous transcatheter hepatic artery infusion chemotherapy (HAIC) with systemic capecitabine monotherapy and camrelizumab for treating unresectable hilar cholangiocarcinoma (HCCA). METHODS: This study retrospectively analyzed patients with unresectable HCCA admitted to Linyi Cancer Hospital in Shandong Province from October 2019 to December 2021. All enrolled patients were treated with HAIC (mFOLFOX7) + camrelizumab for 2-6 cycles and administered systemic therapy with capecitabine and camrelizumab. The objective response rate (ORR), disease control rate (DCR), and adverse reactions of patients were assessed. The Kaplan-Meier method was used to describe overall survival (OS), and univariate and multivariate Cox regression models were utilized to analyze the influencing factors of OS. RESULTS: This study included 34 patients, ORR was 61.76% (21/34), and DCR was 97.06% (33/34) after two HAIC cycles. The median follow-up time was 17.5 months, with an average of 18.32 ± 8.06 months, and the median OS was 20.0 months. HAIC-related adverse reactions included mainly gastrointestinal symptoms and hematological toxicity caused by chemotherapy drugs, all of which were grades 1-2. Further, adverse events for camrelizumab treatment included fatigue, skin rash, and hypothyroidism, all of which were grade <3. Cox regression analysis revealed that the periductal infiltrating type of growth pattern indicated a worse OS, whereas more HAIC cycles (5 ~ 6) were a protective factor for OS. CONCLUSION: HAIC sequentially combined with systemic capecitabine chemotherapy and a programmed death-1 inhibitor displayed favorable effects for unresectable HCCA, with controllable adverse reactions.


Assuntos
Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias dos Ductos Biliares , Capecitabina , Colangiocarcinoma , Artéria Hepática , Infusões Intra-Arteriais , Humanos , Feminino , Masculino , Capecitabina/administração & dosagem , Capecitabina/uso terapêutico , Capecitabina/efeitos adversos , Pessoa de Meia-Idade , Estudos Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias dos Ductos Biliares/tratamento farmacológico , Neoplasias dos Ductos Biliares/patologia , Idoso , Colangiocarcinoma/tratamento farmacológico , Colangiocarcinoma/patologia , Adulto , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/efeitos adversos , Resultado do Tratamento , Taxa de Sobrevida , Seguimentos
7.
J Hazard Mater ; 468: 133860, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38402682

RESUMO

Tire plastic and road-wear particles (TPR-WP) are a current research priority as one of the main environmental sources of microplastics. We selected a unique land use type - desert restoration area, collected soil and dust samples from the Yujing Expressway and its service areas, and analyzed TPR-WP abundance, type, size and morphology by laser direct infrared (LDIR). The abundance of TPR-WP in expressway dust (14,446.87 ± 10,234.24 n/kg) was higher than that in soil (7500 ± 3253.64 n/kg). Random forest model showed that the source of TPR-WP was highly correlated with economic factors and natural climate. Overall, the proportion of small and medium-sized TPR-WP in dust was higher than soil, more than half of the TPR-WP in dust were in 20 - 50 µm range. The proportion of small particle size TPR-WP increased with the rise of elevation. The pollution load index suggested that the survey region was generally at level I risk zone, while the ecological risk index indicated that the pollution level of expressway was III and IV, and the service area was IV. In general, the study was of great significance for clarifying the distribution and risk of TPR-WP in soil and dust of expressways and service areas.

8.
Clin Transl Oncol ; 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38625494

RESUMO

PURPOSE: The treatment of the advanced non-small cell lung cancer (NSCLC) with KRAS mutation has been closely paid more attention. The aim of this study is to investigate the efficacy of different first-line regimens in advanced KRAS-mutated non-small cell lung cancer. METHODS: In our retrospective study, we collected patients with advanced NSCLC with KRAS mutation in Zhejiang Cancer Hospital between January 2015 and May 2023. We analyzed the benefit of different first-line therapy according to theraputic methods and the differential effect of the same treatment method among KRAS-mutated subtypes. We divided the patients into group A (A1, chemotherapy alone; A2, immunotherapy alone) and group B (B1, chemotherapy plus immunotherapy; B2, chemotherapy combined with antiangiogenic therapy; B3, chemotherapy combined with immunotherapy plus antiangiogenic therapy). The Kaplan-Meier survival curve was used to reflect the PFS and OS of different methods. The objective response rate (ORR) and the disease control rate (DCR) were used to evaluated the response. RESULTS: We enrolled 227 patients including eighty-two with KRAS G12C mutation. The ORR and DCR of first-line treatment in the overall population were 32.2% and 80.6% respectively. The median PFS was 6.7 months and the median OS was 17.4 months for the overall population. The PFS of the Group B was significantly better than that of the Group A (7.7 months vs 5.4 months, P = 0.003), while no significant difference in OS was observed (19.4 months vs 15.0 months, P = 0.077). In the Group B, chemotherapy combined immunotherapy with antiangiogenic therapy showed better PFS than chemotherapy plus immunotherapy (14.1 months vs 7.7 months, P = 0.049), and OS also showed that tendency of difference (31.9 months vs 19.3 months, P = 0.158). There was no statistically significant difference between KRAS G12C and non-G12C mutation according to first-line treatment methods, whereas patients with TP53 co-mutation showed a better survival benefit (OS, 23.7 vs 12.5 months, P = 0.023). CONCLUSION: In the first-line treatment, combination regimen has advantages over single regimen. Among them, chemotherapy combined with immunotherapy plus antiangiogenic therapy can achieve significant efficacy benefits.

9.
J Orthop Surg (Hong Kong) ; 32(1): 10225536241248707, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38636168

RESUMO

PURPOSE: To investigate the diagnostic value of anti-Mullerian hormone (AMH) and Inhibin B (InhB) in menopausal women with osteoporosis from the Chinese Daur ethnic group. METHODS: A total of 175 menopausal women were selected and divided into the osteoporosis group (N = 90) and the control group (N = 85). BMD was measured by dual-energy X-ray absorptiometry, and laboratory indicators of osteoporosis, for example, serum osteocalcin (OC), ß-collagen special sequence (ß-CTX), and procollagen type I amino-terminal propeptide (PINP), bone alkaline phosphatase (BALP), AMH, and InhB were measured by commercial kits. The relationship between osteoporosis and AMH or InhB was analyzed. The predictive values of AMH and InhB were reflected by the ROC curve and logistic regression. RESULTS: The level of BMD was decreased and the levels of OC, ß-CTX, PINP, and BALP of the menopausal osteoporosis group were increased. The concentration of AMH and InhB in the menopausal osteoporosis group was decreased and they had connections with each other. AMH and InhB could be used as independent indicators for the occurrence of osteoporosis in menopausal women and their combination had a higher diagnostic value. CONCLUSION: AMH and InhB measurements in menopausal women had a certain clinical significance in the detection of osteoporosis. The occurrence of osteoporosis was related to BMD, OC, ß-CTX, BALP, AMH, and InhB.


Assuntos
Osteoporose Pós-Menopausa , Osteoporose , Humanos , Feminino , Hormônio Antimülleriano , Etnicidade , Inibinas , Menopausa , Fosfatase Alcalina , Osteocalcina , China , Biomarcadores
10.
Environ Sci Pollut Res Int ; 31(20): 29174-29184, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38568309

RESUMO

Pesticide formulations are typically applied as mixtures, and their synergistic effects can increase toxicity to the organisms in the environment. Despite pesticide mixtures being the leading cause of pesticide exposure incidents, little attention has been given to assessing their combined toxicity and interactions. This survey purposed to reveal the cumulative toxic effects of deltamethrin (DEL) and cyazofamid (CYA) on earthworms (Eisenia fetida) by examining multiple endpoints. Our findings revealed that the LC50 values of DEL for E. fetida, following 7- and 14-day exposures, ranged from 887.7 (728-1095) to 1552 (1226-2298) mg kg-1, while those of CYA ranged from 316.8 (246.2-489.4) to 483.2 (326.1-1202) mg kg-1. The combinations of DEL and CYA induced synergistic influences on the organisms. The contents of Cu/Zn-SOD and CarE showed significant variations when exposed to DEL, CYA, and their combinations compared to the untreated group. Furthermore, the mixture administration resulted in more pronounced alterations in the expression of five genes (hsp70, tctp, gst, mt, and crt) associated with cellular stress, carcinogenesis, detoxification, and endoplasmic reticulum compared to single exposures. In conclusion, our comprehensive findings provided detailed insights into the cumulative toxic effects of chemical mixtures across miscellaneous endpoints and concentration ranges. These results underscored the importance of considering mixture administration during ecological risk evaluations of chemicals.


Assuntos
Nitrilas , Oligoquetos , Piretrinas , Animais , Oligoquetos/efeitos dos fármacos , Piretrinas/toxicidade , Nitrilas/toxicidade
11.
Ther Adv Med Oncol ; 16: 17588359241248352, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38736555

RESUMO

Background: While targeted therapy has become the standard treatment for certain non-small-cell lung cancer (NSCLC) patients with gene mutation positivity, there remains a lack of enough reports of the efficacy of mesenchymal-epithelial transition (MET) alterations in the real world. Objectives: We aimed to explore the efficacy and toxicity of targeted therapy in NSCLC patients with different types of MET alterations and hope to provide more clinical medication guidance. Design: Designed different subgroups to compare the efficacy and safety of targeted therapy in NSCLC patients with MET alterations. Methods: We conducted analyses on the efficacy and safety of mesenchymal-epithelial transition factor-tyrosine kinase inhibitor (MET-TKI) therapy in NSCLC patients with MET alterations. Tumor response was evaluated based on the Response Evaluation Criteria in Solid Tumors version 1.1 criteria, and both progression-free survival (PFS) and overall survival were determined using the Kaplan-Meier method. Results: Our study encompassed 116 NSCLC patients with MET alterations, including MET ex14 skipping mutation (n = 50), MET primary amplification (amp) (n = 25), and secondary amp (n = 41). Among treated patients, 34 achieved a partial response, while 52 exhibited stable disease. The overall response rate for the entire cohort was 29.31%, with a disease control rate of 74.14%. A significant difference was observed in the median PFS among patients with MET ex14 skipping mutation, MET primary amplification (amp), and secondary amp (10.4 versus 6.6 versus 4.5 months, p = 0.002). In all, 69 patients experienced drug-related adverse effects, with the most common being peripheral edema (35.34%), nausea and vomiting (21.55%), and fatigue (10.34%). In total, 29 patients (25%) encountered drug-related adverse reactions of grade 3 or higher. Conclusion: MET-TKI therapy works better for MET ex14 skipping mutation than other types of MET gene alteration. In the two MET amplified groups, the secondary amp was less effective. This study may provide more research support for the treatment of these patients.

12.
Environ Sci Pollut Res Int ; 31(32): 44815-44827, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38955968

RESUMO

To reveal the toxicological mechanisms of pesticide mixtures on soil organisms, this study concentrated on evaluating enzymatic activity and gene expression changes in the earthworm Eisenia fetida (Savigny 1826). Despite being frequently exposed to multiple pesticides, including the common combination of abamectin (ABA) and carbendazim (CAR), environmental organisms have primarily been studied for the effects of individual pesticides. Acute toxicity results exhibited that the combination of ABA and CAR caused a synergistic impact on E. fetida. The levels of MDA, ROS, T-SOD, and caspase3 demonstrated a significant increase across most individual and combined groups, indicating the induction of oxidative stress and cell death. Additionally, the expression of three genes (hsp70, gst, and crt) exhibited a significant decrease following exposure to individual pesticides and their combinations, pointing toward cellular damage and impaired detoxification function. In contrast, a noteworthy increase in ann expression was observed after exposure to both individual pesticides and their mixtures, suggesting the stimulation of reproductive capacity in E. fetida. The present findings contributed to a more comprehensive understanding of the potential toxicity mechanisms of the ABA and CAR mixture, specifically on oxidative stress, cell death, detoxification dysfunction, and reproductive capacity in earthworms. Collectively, these data offered valuable toxicological insights into the combined effects of pesticides on soil organisms, enhancing our understanding of the underlying risks associated with the coexistence of different pesticides in natural soil environments.


Assuntos
Benzimidazóis , Carbamatos , Ivermectina , Oligoquetos , Poluentes do Solo , Solo , Animais , Oligoquetos/efeitos dos fármacos , Ivermectina/análogos & derivados , Ivermectina/toxicidade , Carbamatos/toxicidade , Benzimidazóis/toxicidade , Solo/química , Poluentes do Solo/toxicidade , Estresse Oxidativo , Praguicidas/toxicidade
13.
Clin Transl Oncol ; 26(7): 1687-1695, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38363527

RESUMO

BACKGROUND: Anlotinib, as a salvage treatment for patients after failure of third-line or later-line treatments for small cell lung cancer (SCLC), has shown efficacy in patients with brain metastases (BMs). However, the efficacy and safety of anlotinib alone or in combination with immunotherapy for SCLC with BMs remain unclear. METHOD: Patients treated with anlotinib alone or in combination with an immune checkpoint inhibitor (ICI) at the Zhejiang Cancer Hospital between April 2019 and February 2023 were identified. Kaplan-Meier curves were used to describe the progression-free survival (PFS) and intracranial PFS (iPFS). A waterfall diagram was used to indicate changes in intracranial lesions. RESULTS: A total of 48 patients were included; 29 received anlotinib alone, and 19 were administered anlotinib plus ICI. Combination therapy, compared with anlotinib, was associated with significantly longer PFS and iPFS (PFS: 8.1 months vs. 2.5 months, P < 0.001; iPFS: 8.1 months vs. 2.5 months, P = 0.004). Similar results were observed in patients with multiple BMs (PFS: 8.1 months vs. 1.9 months, P = 0.001; iPFS: 8.1 months vs. 1.9 months, P = 0.002). After third-line or later-line treatments, patients treated with ICI plus anlotinib also achieved significant PFS and iPFS benefits (PFS: 8.4 months vs. 2.1 months, P < 0.001; iPFS: 9.2 months vs. 2.1 months, P = 0.002). No new or severe adverse events were observed with combination therapy. CONCLUSION: The combination of anlotinib and ICI has promising intracranial and extracranial efficacy with tolerable toxicity, and may be a therapeutic option for SCLC patients with BMs.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Encefálicas , Inibidores de Checkpoint Imunológico , Indóis , Neoplasias Pulmonares , Quinolinas , Carcinoma de Pequenas Células do Pulmão , Humanos , Indóis/uso terapêutico , Indóis/administração & dosagem , Indóis/efeitos adversos , Quinolinas/uso terapêutico , Quinolinas/efeitos adversos , Quinolinas/administração & dosagem , Masculino , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/patologia , Feminino , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/efeitos adversos , Inibidores de Checkpoint Imunológico/administração & dosagem , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/tratamento farmacológico , Pessoa de Meia-Idade , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Intervalo Livre de Progressão , Estudos Retrospectivos , Adulto , Idoso de 80 Anos ou mais , Estimativa de Kaplan-Meier
14.
Clin Transl Oncol ; 2024 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-38795256

RESUMO

BACKGROUND: The efficacy of afatinib or pyrotinib has been demonstrated in HER2-positive advanced non-small cell lung cancer (NSCLC) patients; however, the efficacy of pyrotinib after afatinib progression has yet to be determined. METHOD: Patients with HER2 mutated advanced lung adenocarcinoma administered afatinib or pyrotinib monotherapy were enrolled. Those who received pyrotinib after afatinib were further analyzed to determine the efficacy and safety of pyrotinib after progression on afatinib. Survival curves were plotted with the Kaplan-Meier method. A swimming plot was used to describe the specific treatments. Additionally, patient-derived tumor organoids (PDTOs) were established from HER2-amplified NSCLC patient samples to investigate the antitumor activity of pyrotinib in HER2-amplified tumor cells in vitro. RESULTS: A total of 99 patients were enrolled, 13 of whom were administered pyrotinib after progression on afatinib. No statistical difference in PFS of pyrotinib was observed between patients whether be treated after afatinib progression or not (6.7 months vs. 4.4 months, P = 0.817), thus indicating that progression on afatinib did not affect the efficacy of pyrotinib. Further analysis was conducted on the former patients, which comprising eight patients administered interval chemotherapy after progression on afatinib. Two patients achieved PR after pyrotinib treatment. No independent factors were found to influence the PFS of pyrotinib. PDTOs confirmed the anti-tumor activity of pyrotinib in NSCLC tumor cells with HER2 amplification. CONCLUSIONS: Progression after prior afatinib treatment does not influence the efficacy of pyrotinib treatment. Pyrotinib may be a salvage option for patients with HER2 mutation who have experienced progression on afatinib.

15.
Food Chem ; 452: 139510, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-38718452

RESUMO

Lettuce, a globally consumed nutritious vegetable, is often linked to concerns regarding pesticide residues. To address this issue, we conducted field trials and utilized dynamiCROP modeling to examine the uptake, distribution, translocation, and dissipation of five pesticides (λ-cyhalothrin, difenoconazole, acetamiprid, dimethomorph, and ß-cypermethrin) commonly detected in lettuce. At harvest, pesticides residues were below the maximum residue limits (MRLs) at 0.05, 0.39, 0.047, 0.72, and 0.072 mg kg-1, respectively. Simulation results elucidated distinct behaviors of the pesticides following application to lettuce foliage across various compartments. However, all pesticides exhibited a common dissipation trend, initially stabilizing or increasing before gradually declining. For all five pesticides, the largest contribution of residues on lettuce leaves came from the leaf surface during the early period after application, and from the soil in the long term. Health risk assessments indicated negligible risks associated with consuming lettuce containing these pesticides, both in the short and long term.


Assuntos
Contaminação de Alimentos , Lactuca , Resíduos de Praguicidas , Lactuca/química , Lactuca/crescimento & desenvolvimento , Lactuca/metabolismo , Contaminação de Alimentos/análise , Resíduos de Praguicidas/análise , Resíduos de Praguicidas/química , Folhas de Planta/química , Folhas de Planta/metabolismo , Humanos , Qualidade de Produtos para o Consumidor
16.
Chemosphere ; 359: 142250, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38710415

RESUMO

Pesticides are typically present as combinations within soil ecosystems and have detrimental effects on untamed surroundings. However, the collective impacts and fundamental mechanisms of pesticides on soil living beings are currently inadequately assessed. In our current work, we evaluated the interactive consequences of clothianidin (CLO) and prochloraz (PRO) on earthworms (Eisenia fetida) using several toxicological tests, such as acute adverse effects, biocatalytic activity, and alterations in transcriptional activity. The findings revealed that CLO (with a 14-day LC50 value of 6.08 mg kg-1) exhibited greater toxicity compared to PRO (with a 14-day LC50 value of 79.41 mg kg-1). Moreover, the combinations of CLO and PRO had synergistic acute effects on E. fetida. Additionally, the activities of POD, CAT, and GST were significantly varied in most instances of single and mixed treatments when compared to the control. Surprisingly, the transcriptional levels of four genes (gst, sod, crt, and ann), related to oxidative load, metabolic detoxification systems, endoplasmic reticulum, and oxytocin neuropeptide, respectively, were also altered in response to single and mixture exposures, as compared to the control. Alterations in enzyme activity and gene transcriptional level could serve as early indicators for detecting co-exposure to pesticides. The findings of this research offered valuable holistic understanding regarding the toxicity of pesticide combinations on earthworms. Further research should be conducted to investigate the persistent effects of pesticide mixtures on terrestrial invertebrates in order to draw definitive conclusions about the associated risks.


Assuntos
Guanidinas , Imidazóis , Neonicotinoides , Oligoquetos , Poluentes do Solo , Tiazóis , Oligoquetos/efeitos dos fármacos , Animais , Neonicotinoides/toxicidade , Tiazóis/toxicidade , Guanidinas/toxicidade , Imidazóis/toxicidade , Poluentes do Solo/toxicidade , Inseticidas/toxicidade , Praguicidas/toxicidade
17.
Sci Total Environ ; 926: 172022, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38552970

RESUMO

While combinations of pesticides better represent actual conditions within aquatic ecosystems, the specific toxic effects of these combinations have not been determined yet. The objective of this research was to assess the combined impact of imazalil and azoxystrobin on the hook snout carp (Opsariichthys bidens) and delve into the underlying causes. Our findings indicated that the 4-day LC50 value for imazalil (1.85 mg L-1) was greater than that for azoxystrobin (0.90 mg L-1). When imazalil and azoxystrobin were combined, they presented a heightened effect on the species. Enzyme activities like SOD, CAT, GST, and CarE, along with androgen and estrogen levels, displayed marked differences in most single and combined treatments in comparison to the baseline group. Moreover, four genes (mn-sod, cu-sod, il-1, and esr) related to oxidative stress, immunity, and the endocrine system exhibited more pronounced expression changes when exposed to combined pesticides rather than individual ones. Our tests revealed that the combined use of imazalil and azoxystrobin had more detrimental effect on aquatic vertebrates than when evaluated individually. This finding suggested that future ecological hazard analyses based only on individual tests might not sufficiently safeguard our aquatic ecosystems.


Assuntos
Carpas , Imidazóis , Praguicidas , Pirimidinas , Estrobilurinas , Poluentes Químicos da Água , Animais , Ecossistema , Superóxido Dismutase , Estresse Oxidativo , Poluentes Químicos da Água/toxicidade
18.
Chemosphere ; 362: 142561, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38851508

RESUMO

Heavy metals and pesticides are significant pollutants in aquatic environments, often leading to combined pollution and exerting toxic effects on aquatic organisms. With the rapid growth of modern industry and agriculture, heavy metal cadmium (Cd) and pesticide triazophos (TRI) are frequently detected together in various water bodies, particularly in agricultural watersheds. However, the combined toxic mechanisms of these pollutants on fish remain poorly understood. This experiment involved a 21-day co-exposure of Cd and TRI to the hook snout carp Opsariichthys bidens to investigate the toxic effects on liver tissues at both enzymatic and transcriptional levels. Biochemical analysis revealed that both individual and combined exposures significantly increased the content or activity of caspase-3 (CASP-3) and malondialdehyde (MDA). Moreover, the impact on these parameters was greater in the combined exposure groups compared to the corresponding individual exposure groups. These findings suggested that both individual and combined exposures could induce mitochondrial dysfunction and lipid peroxidation damage, with combined exposure exacerbating the toxicological effects of each individual pollutant. Furthermore, at the molecular level, both individual and combined exposures upregulated the expression levels of cu-sod, cat, and erß, while downregulating the expression of il-1. Similar to the patterns observed in the biochemical parameters, the combined exposure group exhibited a greater impact on the expression of these genes compared to the individual exposure groups. These results indicated that exposure to Cd, TRI, and their combination induced oxidative stress, endocrine disruption, and immunosuppression in fish livers, with more severe effects observed in the combined exposure group. Overall, the interaction between Cd and TRI appeared to be synergistic, shedding light on the toxic mechanisms by which fish livers responded to these pollutants. These findings contributed to the understanding of mixture risk assessment of pollutants and were valuable for the conservation of aquatic resources.


Assuntos
Cádmio , Fígado , Organotiofosfatos , Triazóis , Poluentes Químicos da Água , Animais , Cádmio/toxicidade , Poluentes Químicos da Água/toxicidade , Organotiofosfatos/toxicidade , Triazóis/toxicidade , Fígado/efeitos dos fármacos , Fígado/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Malondialdeído/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Caspase 3/metabolismo , Caspase 3/genética , Carpas/metabolismo , Carpas/genética , Superóxido Dismutase/metabolismo , Praguicidas/toxicidade
19.
J Ophthalmol ; 2024: 7712516, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39149699

RESUMO

Introduction: Peripheral retinal refraction plays a crucial role in myopia, but the specific mechanism is not clear. We refined the retinal partitions to explore the characteristics of peripheral retinal refraction and its role in emmetropic, low, and moderate myopic children aged 6 to 12 years. Methods: A total of 814 subjects (814 eyes) were enrolled in the study. The participants were divided into three groups according to the central spherical equivalent refraction (SER), which were emmetropia group (E), low myopia group (LM) and moderate myopia group (MM). Multispectral refractive topography (MRT) was used to measure the retinal absolute and relative refractive difference value (RDV) in different regions. The range was divided into superior, inferior, temporal, and nasal RDV (SRDV, IRDV, TRDV, and NRDV) on the basis of several concentric circles extending outward from the macular fovea (RDV15, RDV30, RDV45, RDV30-15, RDV45-30, and RDV-45). Kruskal-Wallis test was used to analyze the differences of peripheral refraction for all the regions among the three groups. Spearman rank correlation was performed to explore correlations between SER and RDV, axial length (AL) and RDV. Results: The absolute value of RDV decreased with increasing degree of myopia in all regions (P < 0.01). Subjects with different refractive degrees had different relative value of RDV. In nasal position within 45° and temporal position within 30°, the peripheral retina exhibited significantly different relative hyperopic refractive status among Group E, Group LM, and Group MM (P < 0.05). SER was negatively correlated with NRDV within 30° (especially in the range of NRDV30-15) (r = -0.141, P < 0.01), positively correlated with TRDV within 15° (r = 0.080, P = 0.023), and not significantly correlated with SRDV and IRDV when the retina was divided into four parts. AL was positively correlated with NRDV within 30° (especially in the range of NRDV30-15) (r = 0.109, P = 0.002), negatively correlated with TRDV within 15° (r = -0.095, P = 0.007). Conclusions: The peripheral defocus has significant implications for the genesis of myopia. The peripheral defocus of the horizontal direction, especially within the range of NRDV30, has greater effect on the development of myopia in children. Higher NRDV30 is associated with lower SER and longer AL.

20.
Sci Total Environ ; 951: 175449, 2024 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-39134278

RESUMO

Enhanced anthropogenic activity strength has altered the watershed particulate transport and material cycle resulting in organic pollutant deposition changes in Dongting Lake associated with unclear ecological risk. In the present study, dual biomarkers i.e. n-alkanes and polycyclic aromatic hydrocarbon (PAHs) were applied in the 210Pb-dated sediment cores for traceability of centennial organic pollutants in the lake mouth area. The partial least squares path model and risk quotients method were used to explore the controlling pathways and ecological risk. The results show a range of sedimentary organic carbon (C), nitrogen (N), and phosphorus (P) was at 1.76-185.66, 0.97-89.80, and 0.01-0.97 g m-2 yr-1 with total reserves of 51.68, 18.44, and 0.27 t ha-1, respectively, over the past 179 years. The presence of PAHs rapidly increased by 2.47 fold from 535.60 ng g-1, while PAHs and carcinogenic PAHs (ΣCPAHs) burial fluxes increased by about 6 and 5 folds, respectively. Accompanied by anthropogenic activities and climate change, the exotic sources gradually becoming predominant. The n-alkane diagnostic ratios indicated a shift of organic matter (OM) from autotrophic bacteria, algae, and phytoplankton-derived sources to macrophyte and terrestrial plants. The exotic origins rose to approximately 73.61 %, while endogenous sources decreased to 26.39 %. The direct effects of anthropogenic activities and their indirect negative impacts on climate and sedimentary structure are the key ways for sediment material loading. The nutrient accumulation in sediments coincides with the lake's eutrophication history over the past decades. The ΣCPAHs accounted for about 89.37 ± 17.14 % of the total TEQ, reflecting a strong ecological risk. The contribution of anthropogenic activities such as fuel usage, fertilizer application, hard pavement coverage, and OM loss from the ecosystem to the sources of organic pollutants and their component types may be a focus of attention in the middle reaches of the Yangtze River plain lake.

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