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1.
J Environ Sci (China) ; 147: 322-331, 2025 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-39003050

RESUMO

To investigate the associations between isocarbophos and isofenphos with impaired fasting glucose (IFG) and type 2 diabetes mellitus (T2DM), and to assess the mediation roles of inflammation cells. There were 2701 participants in the case-control study, including 896 patients with T2DM, 900 patients with IFG, 905 subjects with NGT. Plasma isocarbophos and isofenphos concentrations were measured using gas chromatography and triple quadrupole tandem mass spectrometry. Generalized linear models were used to calculate the relationships between plasma isofenphos and isocarbophos levels with inflammatory factor levels and T2DM. Inflammatory cell was used as mediators to estimate the mediating effects on the above associations. Isocarbophos and isofenphos were positively related with T2DM after adjusting for other factors. The odds ratio (95% confidence interval) (OR (95%CI)) for T2DM was 1.041 (1.015, 1.068) and for IFG was 1.066 (1.009, 1.127) per unit rise in ln-isocarbophos. The prevalence of T2DM increased by 6.4% for every 1 unit more of ln-isofenphos (OR (95% CI): 1.064 (1.041, 1.087)). Additionally, a 100% rise in ln-isocarbophos was linked to 3.3% higher ln-HOMA2IR and a 0.029 mmol/L higher glycosylated hemoglobin (HbA1c) (95% CI: 0.007, 0.051). While a 100% rise in ln-isofenphos was linked to increase in ln-HOMA2 and ln-HOMA2IR of 5.8% and 3.4%, respectively. Furthermore, white blood cell (WBC) and neutrophilic (NE) were found to be mediators in the relationship between isocarbophos and T2DM, and the corresponding proportions were 17.12% and 17.67%, respectively. Isofenphos and isocarbophos are associated with IFG and T2DM in the rural Chinese population, WBC and NE have a significant role in this relationship.


Assuntos
Diabetes Mellitus Tipo 2 , Humanos , Pessoa de Meia-Idade , Masculino , Feminino , Estudos de Casos e Controles , Inseticidas , Glicemia/análise , Malation/análogos & derivados , Compostos Organotiofosforados , China , Adulto , Inflamação
2.
BMC Infect Dis ; 24(1): 1060, 2024 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-39333919

RESUMO

BACKGROUND: Febrile respiratory syndrome (FRS) is often associated with viral infections. The aim of this study was to identify the viral pathogens responsible for FRS in Liaoning Province, China. METHODS: We tested eight respiratory viruses, namely, influenza virus (IFV), rhinovirus (RV), human adenovirus (HAdV), human bocavirus (HBoV), human parainfluenza virus (HPIV), human coronavirus (HCoV), respiratory syncytial virus (RSV), and human metapneumovirus (HMPV), using reverse transcription-polymerase chain reaction (RT-PCR). Statistical analyses were performed using SPSS version 25.0, and the data were plotted using RStudio 4.2.1 software. RESULTS: IFV was the most frequently identified pathogen, followed by RV, HAdV, HBoV, HPIV, HCoV, RSV, and HMPV. RSV/HBoV coinfection occurred most frequently among the mixed cases. The rate of respiratory virus detection was highest in children under one year of age and decreased significantly with age. Seasonal trends showed a peak in virus detection during the winter months. CONCLUSIONS: IFV is the leading cause of FRS in Liaoning Province, China, with single-virus infections prevailing over coinfections. Observations indicate a differential virus detection rate across age groups and seasons, highlighting the need for focused preventive strategies to mitigate the transmission of respiratory viruses, particularly among susceptible populations in the colder season.


Assuntos
Infecções Respiratórias , Humanos , China/epidemiologia , Lactente , Pré-Escolar , Masculino , Feminino , Criança , Adulto , Pessoa de Meia-Idade , Adolescente , Adulto Jovem , Infecções Respiratórias/virologia , Infecções Respiratórias/epidemiologia , Idoso , Estações do Ano , Coinfecção/epidemiologia , Coinfecção/virologia , Viroses/epidemiologia , Viroses/virologia , Vírus/isolamento & purificação , Vírus/classificação , Vírus/genética , Recém-Nascido , Idoso de 80 Anos ou mais
3.
Front Pharmacol ; 15: 1446774, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39314754

RESUMO

Peritoneal dialysis-associated peritonitis (PDAP) is a frequent complication of peritoneal dialysis. The guidelines from the International Society for Peritoneal Dialysis (ISPD) suggest administering teicoplanin through the peritoneal route to treat PDAP, but do not specify the ideal concentration for peritoneal dialysis effluent (PDE). Patients meeting the trial criteria for PDAP in our hospital between July 2022 and December 2023 were enrolled. Data on PDE white blood cell count, PDE neutrophil percentage, clinical symptoms, CRP, and PCT were gathered pre- and post-treatment. Incidences of adverse drug reaction (ADR) and case numbers during treatment were recorded. Subsequently, patients were categorized into cured and uncured groups for evaluating the relationship between PDE teicoplanin concentration and treatment effectiveness. The self-control study results on teicoplanin efficacy indicated intraperitoneal teicoplanin administration achieved an efficacy rate of 88.9% and an ADR incidence of 5.5% in treating PDAP patients. There was no observed correlation between teicoplanin blood concentration and PDE concentration. PDE teicoplanin concentrations on days 1, 3, 5, and 7 post-dosing were higher inthe cured group, with a significant contrast in PDE concentration on day 5 between the 18.98 ± 2.43 mg/L of the cured group and the 12.07 ± 2.68 mg/L of the uncured group. ROC curve revealed a higher likelihood of cure in patients when PDE teicoplanin concentration exceeded 15.138 mg/L on day 5 post-dosing. Univariate and multifactorial studies identified 24-h urine volume and the number of daily abdominal dialysis sessions as influential factors in PDE teicoplanin concentration on day 5. A positive correlation was found between 24-h urine volume and PDE teicoplanin concentration, with PDAP patients having urine volume over 537 mL showing significantly higher drug concentrations. Conversely, the number of daily PDAP sessions was negatively correlated with PDE teicoplanin concentrations, indicating that patients with 1∼3 daily PDAP sessions had notably higher PDE teicoplanin concentrations compared to those with 4∼6 sessions. Therefore, PDAP patients who use intraperitoneal teicoplanin could effectively control infection by monitoring the PDE teicoplanin concentration (>15.138 mg/L) on day 5 after dosing.

4.
Sensors (Basel) ; 24(18)2024 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-39338880

RESUMO

In the process of wireless energy transmission from a Space Solar Power Station (SSPS) to a satellite, the efficiency of energy transmission is closely related to the accuracy of beam control. The existing methods commonly ignore the impact of array position, structural deviation of the transmitting antenna, and modulation errors, which leads to the deviation error in actual energy transmission beams and the reduction of energy transmission efficiency. This paper innovatively proposes a high-precision bi-directional beam-pointing measurement method, which provides a technical basis for advancing the beam-pointing control accuracy from the perspective of improving the beam-pointing measurement accuracy. The method consists of (1) the interferometer goniometry method to realize high-precision guiding beam pointing measurement; and (2) the power field reconstruction method to realize offset angle measurement of the energy-transmitting beam. Simulation results demonstrate that under dynamic conditions, the guiding beam-pointing measurement accuracy of this method reaches 0.05°, which is better than the traditional 0.1° measurement accuracy based on the guiding beam. The measurement accuracy of the offset distance of the energy center is better than 0.11 m, and the measurement accuracy of the offset angle is better than 0.012°.

5.
Inorg Chem ; 63(39): 18182-18192, 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-39297886

RESUMO

Metal-organic frameworks (MOFs) are increasingly becoming an important choice for developing robust and efficient electrocatalysts; therefore, exploring the relationship between the structure, catalytic activity, and stability of MOFs is of great significance. MOFs 1-3 with different spatial configurations are designed and synthesized based on linear pyridine ligands, tetragonal carboxylic acid ligands, and triangular carboxylic acid ligands, while MOF 4 displays a three-dimensional (3D) supramolecule assembled through a mixed-ligand strategy. Compared with MOFs 1-3, MOF 4 has the lowest overpotential of 106 mV (at 10 mA·cm-2) and a Tafel slope of 80.9 mV·dec-1, as well as sturdy long-term stability in the process of oxygen evolution reaction (OER). The presence of dense metal clusters and µ3-O promotes the optimal catalytic performance of MOF 4. Density functional theory (DFT) calculations of MOF 4 demonstrate that the process from O* to OOH* is the rate-determining step. This investigation further reveals the relationship between MOF structural composition and electrocatalytic OER performance and provides an effective strategy for the assembly of MOF-based electrocatalysts.

6.
BMC Womens Health ; 24(1): 514, 2024 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-39272028

RESUMO

BACKGROUND: Advances in minimally invasive surgery and the development of Enhanced Recovery After Surgery (ERAS) have favored the spread of day-surgery programs. Even though Vaginal natural orifice transvaginal endoscopic surgery (vNOTES) is accepted as an innovative treatment for benign ovarian cysts that is rapidly gaining recognition worldwide, the safety and feasibility of same-day surgery (SDS) have yet to be established. OBJECTIVE: This study aimed to evaluate the safety and feasibility of day surgery compared to inpatient surgery of patients undergoing vNOTES for benign ovarian cysts by determining perioperative outcomes. MATERIALS AND METHODS: The study consisted of 213 patients who underwent vNOTES for ovarian cystectomy at a single institution from January 2020 to November 2022. Based on the hospital stay, patients were classified into the same-day surgery group (SDSG) and the inpatient surgery group (ISG); after data processing and screening considering the balance of the two groups, SDSG has 83 samples(n = 83), and ISG has 113 samples(n = 113). The patient's demographic characteristics and follow-up data were collected during the perioperative period by doctors and nurses for medical tracking and analysis purposes and 1-month postoperatively by doctors in charge of their operation. Independent sample t-tests were performed to verify if there was any major difference between these two groups for continuous data like age, BMI, and cyst diameter, and Pearson's chi-squared tests were used to test whether there was a major difference between these two groups for categorical data like cyst count, abdominal surgery history and whether their cyst is bilateral ovarian cysts or not. The association between exhaust time and postoperative characteristics and the association between levels of pain and postoperative characteristics were further analyzed to unveil the confounding factors contributing to the same-day discharge method's quick recovery nature. RESULTS: Upon performing propensity score matching, 196 patients were finally enrolled in this study for the matched comparison, including 83(42.3%) patients in the SDSG and 113(57.7%) patients in the ISG. There was no statistical difference between the two groups in terms of duration of operation (85.0 ± 41.5 min vs. 80.5 ± 33.5 min), estimated blood loss (27.7 ± 28.0 ml vs. 36.3 ± 33.2 ml), preoperative hemoglobin levels (128.8 ± 13.2 g/L vs. 128.6 ± 14.0 g/L), postoperative hemoglobin difference at 24 h (16.5 ± 15.4 g/L vs. 19.3 ± 9.1 g/L), pelvic adhesions (42 (50.6%) vs. 47 (41.6%)), and postoperative complications (7(8.4%) vs. 4(3.5%)). The SDSG group showed less time of feeding/off-bed/exhaust/urination after surgery, shorter hospitalization duration, a lower postoperative 6-hour pain score, and a lower incidence of analgesic drug use. Multiple linear regression analysis showed that advancing the time of postoperative off-bed activity and feeding reduced the postoperative exhaust time by 0.34 (95% CI: 0.185-0.496, 0.34 h, p < 0.001) and 0.299(95% CI: 0.158-0.443, 0.229 h, p = 0.036) hours. In addition, Ordinal logistic regression revealed a correlation between pain scores and bilaterality of cyst, increasing about 25.98 times the risk of pain levels when ovarian cysts are bilateral (OR: 26.98, 95% CI: 1.071-679.859, P = 0.045). CONCLUSION: In this pilot study, same-day discharge after vaginal natural orifice transvaginal endoscopic ovarian cystectomy is safe and feasible. The vNOTES for ovarian cystectomy combined with the same-day discharge shorten the exhaust time and duration of hospitalization, reduce postoperative pain, and lower the use incidence of analgesic drugs.


Assuntos
Estudos de Viabilidade , Cirurgia Endoscópica por Orifício Natural , Cistos Ovarianos , Vagina , Humanos , Feminino , Cistos Ovarianos/cirurgia , Adulto , Estudos Retrospectivos , Cirurgia Endoscópica por Orifício Natural/métodos , Vagina/cirurgia , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Ambulatórios/métodos , Tempo de Internação/estatística & dados numéricos , Alta do Paciente/estatística & dados numéricos , Duração da Cirurgia
8.
Cancers (Basel) ; 16(17)2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39272945

RESUMO

Brain metastasis is the most common intracranial malignancy in adults. The prognosis is extremely poor, partly because most patients have more than one brain lesion, and the currently available therapies are nonspecific or inaccessible to those occult metastases due to an impermeable blood-tumor barrier (BTB). Phosphatidylserine (PS) is externalized on the surface of viable endothelial cells (ECs) in tumor blood vessels. In this study, we have applied a PS-targeting antibody to assess brain metastases in mouse models. Fluorescence microscopic imaging revealed that extensive PS exposure was found exclusively on vascular ECs of brain metastases. The highly sensitive and specific binding of the PS antibody enables individual metastases, even micrometastases containing an intact BTB, to be clearly delineated. Furthermore, the conjugation of the PS antibody with a fluorescence dye, IRDye 800CW, or a radioisotope, 125I, allowed the clear visualization of individual brain metastases by optical imaging and autoradiography, respectively. In conclusion, we demonstrated a novel strategy for targeting brain metastases based on our finding that abundant PS exposure occurs on blood vessels of brain metastases but not on normal brain, which may be useful for the development of imaging and targeted therapeutics for brain metastases.

9.
iScience ; 27(9): 110739, 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39280611

RESUMO

Mast cell tryptases, a family of serine proteases involved in inflammatory responses and cancer development, present challenges in structural characterization and inhibitor development. We employed state-of-the-art protein structure prediction algorithms to model the three-dimensional structures of tryptases α, ß, δ, γ, and ε with high accuracy. Computational docking identified potential substrates and inhibitors, suggesting overlapping yet distinct activities. Tryptases ß, δ, and ε were predicted to act on phenolic compounds, with ß and ε additionally hydrolyzing cyanides. Tryptase δ may possess unique formyl-CoA dehydrogenase activity. Virtual screening revealed 63 compounds exhibiting strong binding to tryptase ß (TPSB2), 12 exceeding the affinity of the known inhibitor. Notably, the top hit (3-chloro-4-methylbenzimidamide) displayed over 10-fold selectivity for tryptase ß over other isoforms. Our integrative approach combining protein modeling, functional annotation, and molecular docking provides a framework for characterizing tryptase isoforms and developing selective inhibitors of therapeutic potential in inflammatory and cancer conditions.

10.
J Mater Chem B ; 2024 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-39283590

RESUMO

Chirality is a ubiquitous phenomenon in nature. The advent of nanomaterials has led to a gradual evolution of chiral studies from the molecular scale to the nanoscale. The emergence of carbon dots (CDs) has inaugurated a novel domain in the scientific and technological realms of carbon nanomaterials. In recent years, CDs have attracted increasing attention due to their luminescent properties, excellent biocompatibility and remarkable bioactivity. However, little attention has been paid to the chirality of the CDs and, in particular, the differences between CDs synthesized from racemic compounds and other chiral CDs, as well as the differences in the biological effects of chiral CDs, remain to be explored. Here, chiral CDs were synthesized from L-/D-/DL-arginine, and the differences in various aspects of chiral CDs were evaluated. We found that L-CDs without extreme differences in structure had brighter fluorescence and a more significant ability of NO generation and lipid droplet inhibition than the other two chiral CDs. Combined with its better drug loading and release ability, we validated its superior efficacy in tumor treatment. Therefore, this study provides a basis for further research on chiral carbon dots and their differences.

11.
Front Pharmacol ; 15: 1447283, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39221139

RESUMO

Background: Stephania tetrandra has been used for treating rheumatic diseases for thousands of years in rural areas of China. Several studies have found that tetrandrine and fangchinoline can inactivate the PI3K/Akt signaling pathway by reducing the expression and phosphorylation of AKT. However, the mechanism underlying the therapeutic actions of S. tetrandra on RA is not well known. Methods: In this study, we determined the molecular mechanism of the therapeutic effects of the multiple ingredients of S. tetrandra extract (STE) on collagen-induced arthritic (CIA) rats by integrating pharmacometabolomics, proteomics, and PTMomics. Results: In the multi-omics joint analysis, first, the expression signatures of proteins, PTMs, metabolites, and STE ingredients were profiled in CIA rats PBMCs that underwent STE treatment. Bioinformatics analysis were subsequently probed that STE mainly regulated tryptophan metabolism, inflammatory response, and cell adhesion pathways in CIA rats. The interrelated pathways were further constructed, and the findings revealed that STE attenuated the inflammatory response and proliferation of PBMCs in CIA rats by mediating the key targets of the PI3K/Akt pathway, including Hint1, ACP1, FGR, HSP90@157W + dioxidation, and Prkca@220N + 845.4540 Da. The rheumatic functions of Hint1 and ACP1 were further confirmed by applying a transcriptomic data of RA patients who clinically received abatacept therapy. Furthermore, a cross-ome correlation analysis was performed and major in vivo ingredients of STE, including coclaurine-N-glucuronide, Me,coclaurine-O-glc, N-gluA-schefferine, corydamine, corypamine, tetrandrine, and fangchiniline, were found to act on these targerts to inactivate the PI3K/Akt pathway. Conclusion: These results elucidated the molecular mechanism by which the ingredients of STE mediate the expression of the key targets in the PI3K/Akt pathway, leading to anti-rheumatic functions. The findings of this study provided new insights into the synergistic effect of STE against arthritis in rats.

12.
Heliyon ; 10(17): e36744, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-39263074

RESUMO

Tripartite motif-containing protein 59 (TRIM59) is a biomarker for multiple tumors with crucial roles. However, the specific role of TRIM59 in germ cells remains largely unknown. Here, we investigated the effects and underlying regulatory mechanisms of TRIM59 on germ cells using the mouse spermatogonial cell line GC-1. Our results demonstrated that TRIM59 promoted proliferation and inhibited apoptosis of GC-1 cells. Mechanistically, TRIM59 maintained GC-1 cell behaviors through ubiquitination of AXIN1 to activate ß-catenin signaling. Furthermore, activation of ß-catenin signaling reversed the effects mediated by Trim59 knockdown in GC-1 cells. Collectively, our study revealed a major role and regulatory mechanism of TRIM59 in GC-1 cells, which sheds new light on the molecular pathogenesis of defects in spermatogenesis and may provide therapeutic targets for treatment of male infertility.

13.
Front Oncol ; 14: 1415859, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39290245

RESUMO

Hepatocellular Carcinoma (HCC), the most common primary liver cancer, is a significant contributor to worldwide cancer-related deaths. Various medical imaging techniques, including computed tomography, magnetic resonance imaging, and ultrasound, play a crucial role in accurately evaluating HCC and formulating effective treatment plans. Artificial Intelligence (AI) technologies have demonstrated potential in supporting physicians by providing more accurate and consistent medical diagnoses. Recent advancements have led to the development of AI-based multi-modal prediction systems. These systems integrate medical imaging with other modalities, such as electronic health record reports and clinical parameters, to enhance the accuracy of predicting biological characteristics and prognosis, including those associated with HCC. These multi-modal prediction systems pave the way for predicting the response to transarterial chemoembolization and microvascular invasion treatments and can assist clinicians in identifying the optimal patients with HCC who could benefit from interventional therapy. This paper provides an overview of the latest AI-based medical imaging models developed for diagnosing and predicting HCC. It also explores the challenges and potential future directions related to the clinical application of AI techniques.

14.
ACS Omega ; 9(38): 39715-39723, 2024 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-39346814

RESUMO

The importance of selectively oxidizing aniline into value-added chemicals azoxybenzene and nitrobenzene is well-recognized in organic synthesis. However, the lack of control over selectivity and the complex synthesis of costly catalysts significantly hinder these reactions' industrial applications. In this work, an environmentally friendly approach was developed for the selective oxidization of substituted anilines. This method involves adjusting the strength of alkalinity with peroxide as the oxidant, without the addition of any metals or additives. A mild base (NaF) facilitated azoxybenzene formation, while a stronger base (NaOMe) enabled the synthesis of nitroaromatics. These protocols are user-friendly and scalable, accommodating various substitution patterns and functional groups, yielding products with high to excellent yields. The findings of this work present a framework for investigating base catalysis in organic synthesis and provide a viable and effective approach for selectively oxidizing aniline.

15.
Poult Sci ; 103(10): 104045, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39094493

RESUMO

Marek's disease (MD), an immunosuppression disease induced by Marek's disease virus (MDV), is one of the significant diseases affecting the health and productive performance of poultry. The roles of circular RNAs (circRNAs) in MD development were poorly understood. In this study, we found a circRNA derived from exon 6 of RUNX family transcription factor 2 (RUNX2) gene, named circRUNX2.2, was highly expressed in chicken tumorous spleens (TS) induced by MDV. Through fluorescence in situ hybridization and nuclear-cytoplasmic separation assay, we determined circRUNX2.2 was mainly located in the nucleus. Knockout experiments confirmed that the flanking complementary sequences (RCMs) mediated its circularization. Gain of function assay and dual luciferase reporter gene assay revealed that circRUNX2.2 could promote the expression of RUNX2 via binding with its promoter region. RNA antisense purification assay and mass spectrometry assay showed circRUNX2.2 could recruit proteins such as CHD9 protein. Knocking down CHD9 expression decreased the expression of RUNX2 gene, which confirmed the positive regulation that circRUNX2.2 on RUNX2 expression was probably facilitated via recruiting CHD9 protein. Functional experiments showed that circRUNX2.2 promoted the proliferation of the MD lymphoma-derived chicken cell line, MDCC-MSB1, which confirmed the potential oncogenic role of circRNX2.2 in tumor development. In conclusion, we found that the RUNX2-derived circRUNX2.2 can positively regulate the transcription of the parental gene RUNX2 in a cis-acting manner. The high expression of circRUNX2.2 in MD tumor tissues indicated that it might mediate MD lymphoma progression.


Assuntos
Proteínas Aviárias , Galinhas , Subunidade alfa 1 de Fator de Ligação ao Core , Doença de Marek , RNA Circular , Animais , Galinhas/genética , Doença de Marek/genética , Doença de Marek/virologia , Doença de Marek/metabolismo , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Proteínas Aviárias/genética , Proteínas Aviárias/metabolismo , RNA Circular/genética , RNA Circular/metabolismo , Doenças das Aves Domésticas/genética , Doenças das Aves Domésticas/metabolismo , Doenças das Aves Domésticas/virologia , Regulação da Expressão Gênica
16.
Ecotoxicol Environ Saf ; 283: 116831, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-39151374

RESUMO

BACKGROUND: Aflatoxin B1, which can penetrate the blood-brain barrier and kill neural cells, can contaminate traditional herbal medicines, posing a significant risk to human health. The present study examined cellular, cognitive and behavioral consequences of aflatoxin B1 contamination of the anti-osteoporotic medicine Radix Dipsaci. METHODS: A mouse model of osteoporosis was created by treating the animals with all-trans-retinoic acid. Then the animals were treated intragastically with water decoctions of Radix Dipsaci that contained detectable aflatoxin B1 or not. The animals were compared in terms of mineral density and mineral salt content of bone, production of pro-inflammatory factors, neurogenesis and microglial activation in hippocampus, as well as behavior and cognitive function. RESULTS: Contamination of Radix Dipsaci with aflatoxin B1 significantly reduced the medicine's content of bioactive saponins. It destroyed the ability of the herbal decoction to improve mineral density and mineral salt content in the bones of diseased mice, and it induced the production of the oxidative stress marker malondialdehyde as well as the pro-inflammatory cytokines interleukin-1ß and tumor necrosis factor-α. Aflatoxin B1 contamination inhibited formation of new neurons and increased the proportion of activated microglia in the hippocampus. These neurological changes were associated with anhedonia, behavioral despair, and deficits in short-term memory and social memory. CONCLUSION: Contamination of Radix Dipsaci with aflatoxin B1 not only eliminates the herbal decoction's anti-osteoporotic effects, but it also induces neurotoxicity that can lead to cognitive decline and behavioral abnormalities. Such contamination should be avoided through tightly regulated production and quality control of medicinal herbs.


Assuntos
Aflatoxina B1 , Cognição , Modelos Animais de Doenças , Hipocampo , Neurogênese , Osteoporose , Animais , Hipocampo/efeitos dos fármacos , Aflatoxina B1/toxicidade , Camundongos , Osteoporose/tratamento farmacológico , Osteoporose/induzido quimicamente , Cognição/efeitos dos fármacos , Neurogênese/efeitos dos fármacos , Dipsacaceae/química , Masculino , Contaminação de Medicamentos , Medicamentos de Ervas Chinesas/farmacologia
17.
Eur J Med Chem ; 277: 116751, 2024 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-39128328

RESUMO

SMARCA2 and SMARCA4 are the mutually exclusive catalytic subunits of the mammalian Switch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complex, and have recently been considered as attractive synthetic lethal targets for PROTAC-based cancer therapy. However, the potential off-tissue toxicity towards normal tissues remains a concern. Here, we optimize a GSH-inducible SMARCA2/4-based PROTAC precursor with selective antitumor activity towards lung cancer cells and negligible cytotoxicity towards normal cells in both in vitro and in vivo studies. The precursor is not bioactive or cytotoxic, but preferentially responds to endogenous GSH in GSH-rich lung cancer cells, releasing active PROTAC to degrade SMARCA2/4 via PROTAC-mediated proteasome pathway. Subsequent xenograft model study reveals that selective SMARCA2/4 degradation in lung tumors triggers DNA damage and apoptosis, which significantly inhibits lung cancer cell proliferation without obvious adverse events towards normal tissues. This study exemplifies the targeted degradation of SMARCA2/4 in lung cancer cells by the GSH-responsive PROTAC precursor, highlighting its potential as an encouraging cancer therapeutic strategy.


Assuntos
Antineoplásicos , Proliferação de Células , Glutationa , Neoplasias Pulmonares , Fatores de Transcrição , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Glutationa/metabolismo , Fatores de Transcrição/metabolismo , Fatores de Transcrição/antagonistas & inibidores , Proliferação de Células/efeitos dos fármacos , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Animais , Apoptose/efeitos dos fármacos , Camundongos , Proteínas Nucleares/metabolismo , Proteínas Nucleares/antagonistas & inibidores , Relação Dose-Resposta a Droga , Estrutura Molecular , Relação Estrutura-Atividade , Ensaios de Seleção de Medicamentos Antitumorais , Linhagem Celular Tumoral , DNA Helicases/metabolismo , DNA Helicases/antagonistas & inibidores , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/patologia , Neoplasias Experimentais/metabolismo
18.
Cell Rep ; 43(8): 114588, 2024 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-39110594

RESUMO

Plant diseases caused by fungal pathogens pose a great threat to crop production. Conidiation of fungi is critical for disease epidemics and serves as a promising drug target. Here, we show that deacetylation of the FolTFIIS transcription elongation factor is indispensable for Fusarium oxysporum f. sp. lycopersici (Fol) conidiation. Upon microconidiation, Fol decreases K76 acetylation of FolTFIIS by altering the level of controlling enzymes, allowing for its nuclear translocation by FolIws1. Increased nuclear FolTFIIS enhances the transcription of sporulation-related genes and, consequently, enables microconidia production. Deacetylation of FolTFIIS is also critical for the production of macroconidia and chlamydospores, and its homolog has similar functions in Botrytis cinerea. We identify two FolIws1-targeting chemicals that block the conidiation of Fol and have effective activity against a wide range of pathogenic fungi without harm to the hosts. These findings reveal a conserved mechanism of conidiation regulation and provide candidate agrochemicals for disease management.


Assuntos
Proteínas Fúngicas , Fusarium , Esporos Fúngicos , Fusarium/metabolismo , Fusarium/efeitos dos fármacos , Fusarium/genética , Fusarium/patogenicidade , Esporos Fúngicos/metabolismo , Esporos Fúngicos/efeitos dos fármacos , Proteínas Fúngicas/metabolismo , Proteínas Fúngicas/genética , Acetilação , Doenças das Plantas/microbiologia , Núcleo Celular/metabolismo , Regulação Fúngica da Expressão Gênica , Transporte Ativo do Núcleo Celular , Botrytis/genética , Botrytis/metabolismo , Botrytis/efeitos dos fármacos
19.
J Hazard Mater ; 479: 135579, 2024 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-39216247

RESUMO

Exposure to fine particulate matter (PM2.5) poses numerous health risks, with oxidative potential (OP) serving as a critical marker of its toxicity. Synthetic phenolic antioxidants (SPAs) and bisphenols (BPs) influence reactive oxygen species (ROS) levels in PM2.5, and exposure to these compounds induces oxidative stress in organisms, thereby potentially affecting the OP of PM2.5. We detected 26 phenols (including 12 SPAs, 5 transformation products (TPs), and 9 BPs) in PM2.5 sample collected from October 2018 to September 2021 in Wuhan, China. Among them, 19 substances were detected at a detection frequency greater than 50 % in PM2.5 sample. AO 2246 and BHT were the main components of SPAs, and BHT-Q and BPA had the highest concentrations in TPs and BPs, respectively. PM2.5 mass concentrations and phenolic levels were higher in winter and autumn. Substances within groups were strongly correlated, suggesting the same or similar source of exposure. This finding aid in more precise pollution source identification and is crucial for comprehensively evaluating their combined health effects. Furthermore, we determined the OP of PM2.5 and found that BPs were related to increased OP and ROS. This suggests that the toxicity of PM2.5 is influenced not only by its concentration but also by its chemical composition, with BPs potentially enhancing its toxic effects. These factors should be fully considered when assessing the health impacts of PM2.5.


Assuntos
Poluentes Atmosféricos , Material Particulado , Fenóis , Estações do Ano , Material Particulado/análise , Material Particulado/toxicidade , Fenóis/análise , Fenóis/toxicidade , Poluentes Atmosféricos/análise , Poluentes Atmosféricos/toxicidade , China , Antioxidantes/análise , Antioxidantes/química , Espécies Reativas de Oxigênio/metabolismo , Monitoramento Ambiental , Estresse Oxidativo/efeitos dos fármacos , Oxirredução
20.
Psychol Health ; : 1-20, 2024 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-39119793

RESUMO

OBJECTIVE: Health-promoting behaviors carry substantial significance for miners' overall health and well-being. This study aimed to examine the association between cumulative risk (CR) and miners' health-promoting behaviors and test the mediating role of health beliefs in this relationship. METHODS: Data were collected from a sequential survey conducted among 712 frontline miners (Mage=41.7 ± 10.1 years) in China. The survey entailed online questionnaire measurements at three distinct time points, each spaced two weeks apart. This study utilized the conceptual model of health-promoting behaviors, the CR model, and structural equation modeling in the analysis of relationships. RESULTS: CR was negatively related to health-promoting behaviors, with a negative acceleration effect. CR was positively associated with perceived threat in a gradient effect, while negatively associated with perceived benefits in a gradient effect. Furthermore, CR was negatively related to self-efficacy, following a negative acceleration effect. Perceived threat, perceived benefits, and self-efficacy emerged as significant mediators in the relationship between CR and health-promoting behaviors. CONCLUSION: This study highlights the critical role of considering both CR and health beliefs in shaping miners' health-promoting behaviors. Understanding these dynamics is pivotal for developing interventions to enhance miners' health and well-being.

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