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1.
J Ethnopharmacol ; 336: 118733, 2025 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-39181281

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Smilax glabra rhizome has a long history been used for clinical purposes in traditional Chinese medicinal for treating various inflammatory conditions. Engeletin1 (ENG) is one of the most abundant bioactive compounds found in Smilax glabra rhizome, with anti-inflammatory, antioxidant, and ulcer-preventing activities. AIM OF THE STUDY: The purpose of this study was to investigate the ability of ENG to alleviate inflammatory symptoms and improve epithelial barrier integrity utilize a 2,4,6-trinitrobenzene sulfonic acid2 (TNBS)-induced murine model in Crohn's disease3 (CD)-like colitis, and to characterize the underlying anti-inflammatory mechanisms of action. MATERIALS AND METHODS: A colitis model was established in BALB/c mice and treated with ENG for 7 days. RAW264.7 macrophages were pre-treated with ENG and lipopolysaccharide4 (LPS) stimulation. The mice's weight and colon length were assessed. qPCR and Western blotting were used to analyze gene expression and TLR4-NFκB pathway. Flow cytometry was used to analyze the polarization states of the macrophages. RESULTS: Treatment with ENG was sufficient to significantly alleviate symptoms of inflammation and colonic epithelial barrier integrity in treated mice. Significant inhibition of TNF-α, IL-1ß, and IL-6 expression was observed following ENG treatment in vivo and in vitro. ENG was also determined to be capable of inhibiting the expression of iNOS and CD86, inhibited M1 macrophage polarization in vitro, as well as the TLR4-NFκB signaling pathway. Molecular docking showed a highly stable binding between ENG and TLR4. CONCLUSION: ENG has been proven to alleviate inflammation and ameliorate the damage of epithelial barrier in CD-like colitis. ENG also suppressed the M1 macrophages polarization and the inhibited inflammatory cytokines. TLR4-NFκB signaling pathway, especially TLR4, may be the target of ENG. These data offer a new insight into the therapeutic mechanisms of ENG.


Assuntos
Anti-Inflamatórios , Colite , Doença de Crohn , NF-kappa B , Transdução de Sinais , Receptor 4 Toll-Like , Ácido Trinitrobenzenossulfônico , Animais , Masculino , Camundongos , Anti-Inflamatórios/farmacologia , Colite/tratamento farmacológico , Colite/induzido quimicamente , Colite/metabolismo , Colo/efeitos dos fármacos , Colo/patologia , Colo/metabolismo , Doença de Crohn/tratamento farmacológico , Citocinas/metabolismo , Modelos Animais de Doenças , Flavonóis , Glicosídeos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos Endogâmicos BALB C , NF-kappa B/metabolismo , Células RAW 264.7 , Transdução de Sinais/efeitos dos fármacos , Smilax/química , Receptor 4 Toll-Like/metabolismo
2.
J Occup Health ; 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39302192

RESUMO

OBJECTIVES: This study was to investigate factors that influence the sleep quality and menstrual cycles of female rotating-shift nurses. METHODS: A cross-sectional study was conducted in which 213 female rotating-shift nurses between the ages of 20 and 45 were recruited from a medical center in Taiwan from November 1, 2023, to December 31, 2023. Binary logistic regression analysis was performed with regard to sleep quality or menstrual cycle. RESULTS: Female rotating-shift nurses who perceived a higher level of stress (p < .001), were late chronotypes (p = .020), or were working the night shift (p = .006) were more likely to have poor sleep quality. Late-type nurses working the day shift were more likely to have poor sleep quality than were early- and intermediate-type nurses (p < .001). With regard to menstrual cycles, female rotating-shift nurses who perceived a higher level of stress (p = .008), were working the night shift (p < .001), or had poor sleep quality (p = .001) were more likely to have irregular menstrual cycles. Late-type nurses working the day shift were more likely to have irregular menstrual cycles than were early- and intermediate-type nurses (p = .013). CONCLUSIONS: A higher likelihood of poor sleep quality was found in female rotating-shift nurses when they perceived high levels of stress, and the interactions between chronotype and shift type could influence sleep quality. Shift type and the interactions between chronotype and shift type could also influence menstrual regularity.

3.
Int J Biol Macromol ; 279(Pt 4): 135376, 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39244119

RESUMO

Adipocyte-secreted factors intricately regulate adipose tissue function, and the underlying molecular mechanisms are only partially understood. However, the function of PRELP, which is a key component of the extracellular matrix (ECM) in adipocytes, remains largely unknown. In this study, we demonstrate that PRELP was upregulated in both obese humans and mice, which exhibited a positive correlation with metabolic disorders. PRELP knockout could resist HFD-induced obesity and inhibit adipocyte differentiation. PRELP knockout improved glucose tolerance, insulin sensitivity and alleviated adipose tissue fibrosis. Mechanistically, PRELP was secreted into the ECM and bound to the extracellular domain of its receptor p75NTR in adipocytes, which further activated the FAK/MAPK (JNK, p38 MAPK, ERK1/2) signaling pathway, promoting adipocyte differentiation and exacerbating adipocyte fibrosis. Adipocyte PRELP plays a pivotal role in regulating obesity and adipose tissue fibrosis through an autocrine manner, and PRELP may be a therapeutic target for obesity and its related metabolic disorders.

4.
Environ Int ; 191: 108966, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39167854

RESUMO

Triclosan (TCS) is an environmental pollutant. In recent years, there has been increasing level of concern regarding the potential toxicity of TCS in animals and humans, especially its effects on the nervous system. However, whether TCS induces ADHD-like behaviour and the mechanism by which it affects neural function are unclear. The impact of 60 days of continuous exposure to TCS on the behaviour of offspring rats was assessed in this research. According to the results of this study, TCS exposure led to ADHD-like behaviour in offspring rats and activated microglia in the prefrontal cortex (PFC), inducing inflammatory factor release. In vitro studies showed that TCS increased the levels of inflammatory cytokines, including interleukin (IL)-1ß, IL-6 and tumour necrosis factor (TNF)-α, in HMC3 cells. More importantly, we found that TCS regulated the STAT3 pathway by upregulating PKM2 via hnRNPA1. In summary, this study suggested that TCS can induce ADHD-like behaviour in offspring rats and continuously activate HMC3 microglia through the hnRNPA1-PKM2-STAT3 feedback loop, promoting inflammatory cytokine secretion.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Microglia , Fator de Transcrição STAT3 , Triclosan , Animais , Ratos , Transtorno do Deficit de Atenção com Hiperatividade/induzido quimicamente , Fator de Transcrição STAT3/metabolismo , Microglia/efeitos dos fármacos , Microglia/metabolismo , Triclosan/toxicidade , Masculino , Citocinas/metabolismo , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/metabolismo , Feminino , Ratos Sprague-Dawley , Poluentes Ambientais/toxicidade , Comportamento Animal/efeitos dos fármacos , Humanos , Transdução de Sinais/efeitos dos fármacos
5.
Adv Sci (Weinh) ; : e2403347, 2024 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-39120546

RESUMO

The highly immunosuppressive tumor microenvironment (TME) restricts the efficient activation of immune responses. To restore the surveillance of the immune system for robust activation, vast efforts are devoted to normalizing the TME. Here, a manganese-doped layered double hydroxide (Mn-LDH) is developed for potent anti-tumor immunity by reversing TME. Mn-LDH is synthesized via a one-step hydrothermal method. In addition to the inherent proton neutralization capacity of LDH, the introduction of manganese oxide endows LDH with an additional ability to produce oxygen. Mn-LDH effectively releases Mn2+ and Mg2+ upon exposure to TME with high levels of H+ and H2O2, which activates synthase-stimulator of interferon genes pathway and maintains the cytotoxicity of CD8+ T cells respectively, achieving a cascade-like role in innate and adaptive immunity. The locally administered Mn-LDH facilitated a "hot" network consisting of mature dendritic cells, M1-phenotype macrophages, as well as cytotoxic and helper T cells, significantly inhibiting the growth of primary and distal tumors. Moreover, the photothermal conversion capacity of Mn-LDH sparks more robust therapeutic effects in large established tumor models with a single administration and irradiation. Overall, this study guides the rational design of TME-modulating immunotherapeutics for robust immune activation, providing a clinical candidate for next-generation cancer immunotherapy.

6.
Ecotoxicol Environ Saf ; 282: 116766, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-39047361

RESUMO

In recent years, exposure to triclosan (TCS) has been linked to an increase in psychiatric disorders. Nonetheless, the precise mechanisms of this occurrence remain elusive. Therefore, this study developed a long-life TCS-exposed rat model, an SH-SY5Y cell model, and an atomoxetine hydrochloride (ATX) treatment model to explore and validate the neurobehavioral mechanisms of TCS from multiple perspectives. In the long-life TCS-exposed model, pregnant rats received either 0 mg/kg (control) or 50 mg/kg TCS by oral gavage throughout pregnancy, lactation, and weaning of their offspring (up to 8 weeks old). In the ATX treatment model, weanling rats received daily injections of either 0 mg/kg (control) or 3 mg/kg ATX via intraperitoneal injection until they reached 8 weeks old. Unlike the TCS model, ATX exposure only occurred after the pups were weaned. The results indicated that long-life TCS exposure led to attention-deficit hyperactivity disorder (ADHD)-like behaviors in male offspring rats accompanied by dopamine-related mRNA and protein expression imbalances in the prefrontal cortex (PFC). Moreover, in vitro experiments also confirmed these findings. Mechanistically, TCS reduced dopamine (DA) synthesis, release, and transmission, and increased reuptake in PFC, thereby reducing synaptic gap DA levels and causing dopaminergic deficits. Additional experiments revealed that increased DA concentration in PFC by ATX effectively alleviated TCS-induced ADHD-like behavior in male offspring rats. These findings suggest that long-life TCS exposure causes ADHD-like behavior in male offspring rats through dopaminergic deficits. Furthermore, ATX treatment not only reduce symptoms in the rats, but also reveals valuable insights into the neurotoxic mechanisms induced by TCS.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Dopamina , Córtex Pré-Frontal , Efeitos Tardios da Exposição Pré-Natal , Triclosan , Animais , Triclosan/toxicidade , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/metabolismo , Transtorno do Deficit de Atenção com Hiperatividade/induzido quimicamente , Feminino , Ratos , Gravidez , Masculino , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Dopamina/metabolismo , Ratos Sprague-Dawley , Comportamento Animal/efeitos dos fármacos , Cloridrato de Atomoxetina , Humanos
7.
Biology (Basel) ; 13(7)2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-39056660

RESUMO

BACKGROUND: Chemotherapy is the main first-line treatment, but there is a problem of adverse reactions to systemic drugs. Chemotherapeutic agents may cause adverse effects on the body, influencing the prognosis. Whether the clinical application of anthracyclines is associated with an increased arrhythmic risk remains controversial. To evaluate the arrhythmic risk of anthracyclines as a class, and the comparative risk for each drug, we conducted a systematic review, meta-analysis, and network meta-analysis. METHODS: PubMed, Web of Science, EMBASE, and the Cochrane Library were searched, up to March 2022, for randomized controlled trials, cohort studies, and case-control studies that investigated the association between anthracyclines treatment and the risk of arrhythmia. We followed the PRISMA 2020 guidelines for data selection and extraction. Outcomes were pooled using fixed effects models in cohort studies and randomized controlled studies, and random models in single-arm studies. Direct and indirect comparisons in network meta-analysis were performed using frequentist methods. RESULTS: In total, 4 cohort studies, 8 RCTs, and 18 single-arm studies were included in our analysis. Anthracyclines' use was associated with a statistically significant 90% increase in the risk of arrhythmia (odds ratio [OR] 1.90; 95% confidence interval [CI] 1.62-2.24) and a 114% increase in the risk of supraventricular arrhythmia (OR 2.14; 95% CI 1.18-3.89). And the single-arm studies also indicated that the incidence of arrhythmia rate is 20% and the 95% CI is 15/100-25/100. Epirubicin ranked most likely to have the highest risk of arrhythmia compared with non-anthracycline antineoplastic drugs in the analysis (OR 43.07 [95% CI 2.80-2105.83]) by network meta-analysis. CONCLUSIONS: Our findings show a significant association between anthracyclines' use and an increased risk of arrhythmia, especially supraventricular arrhythmia. Epirubicin ranked with the highest probability of arrhythmia. These results indicated that cardiac rhythm should be strictly monitored during the application of anthracyclines in clinical practice, and a possible therapy for anthracycline-associated arrhythmia should be explored. Molecular imaging technology is an important means to study the mechanism of drug action on cardiac electrophysiology in the future. By imaging molecular targets in cardiac cells, the effects of drugs on the electrophysiological properties of cardiac cells can be understood, which provides information for the development of safer and more effective drugs.

8.
Sci Total Environ ; 942: 173739, 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-38839007

RESUMO

Triclosan (TCS), a commonly used antibacterial agent, is associated with various harmful effects on mammalian neurodevelopment, particularly when exposed prenatally. This study investigated the impact of long-term exposure to TCS on the prefrontal cortex development in adolescent mice. We evaluated the motor ability, motor coordination, and anxiety behavior of mice using open field tests (OFT) and elevated cross maze tests (EPM). An increase in movement distance, number of passes through the central area, and open arm retention time was observed in mice treated with TCS. Hematoxylin eosin staining and Nissl staining also showed significant adverse reactions in the brain tissue of TCS-exposed group. TCS induced microglia activation and increased inflammatory factors expression in the prefrontal cortex. TCS also increased the expression of pyruvate kinase M2 (PKM2), thereby elevating the levels of PKM2 dimer, which entered the nucleus. Treatment with TEPP46 (PKM2 dimer nuclear translocation inhibitor) blocked the expression of inflammatory factors induced by TCS. TCS induced the phosphorylation of nuclear signal transducer and activator of transcription 3 (STAT3) in vivo and in vitro, upregulating the levels of inflammatory cytokines. The results also demonstrated the binding of PKM2 to STAT3, which promoted STAT3 phosphorylation at the Tyr705 site, thereby regulating the expression of inflammatory factors. These findings highlight the role of PKM2-regulated STAT3 phosphorylation in TCS-induced behavioral disorders in adolescents and propose a reliable treatment target for TCS.


Assuntos
Microglia , Doenças Neuroinflamatórias , Piruvato Quinase , Fator de Transcrição STAT3 , Triclosan , Animais , Triclosan/toxicidade , Camundongos , Microglia/efeitos dos fármacos , Piruvato Quinase/metabolismo , Fator de Transcrição STAT3/metabolismo , Fosforilação , Doenças Neuroinflamatórias/induzido quimicamente , Anti-Infecciosos Locais/toxicidade , Masculino
9.
Materials (Basel) ; 17(10)2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38793418

RESUMO

This study aims to explore the static mechanical characteristics of coral aggregate seawater shotcrete (CASS) using an appropriate mix proportion. The orthogonal experiments consisting of four-factor and three-level were conducted to explore an optimal mix proportion of CASS. On a macro-scale, quasi-static compression and splitting tests of CASS with optimal mix proportion at various curing ages employed a combination of acoustic emission (AE) and digital image correlation (DIC) techniques were carried out using an electro-hydraulic servo-controlled test machine. A comparative analysis of static mechanical properties at different curing ages was conducted between the CASS and ordinary aggregate seawater shotcrete (OASS). On a micro-scale, the numerical specimens based on particle flow code (PFC) were subjected to multi-level microcracks division for quantitive analysis of the failure mechanism of specimens. The results show that the optimal mix proportion of CASS consists of 700 kg/m3 of cementitious materials content, a water-binder ratio of 0.45, a sand ratio of 60%, and a dosage of 8% for the accelerator amount. The tensile failure is the primary failure mechanism under uniaxial compression and Brazilian splitting, and the specimens will be closer to the brittle material with increased curing age. The Brazilian splitting failure caused by the arc-shaped main crack initiates from the loading points and propagates along the loading line to the center. Compared with OASS, the CASS has an approximately equal early and low later strength mainly because of the minerals' filling or unfilling effect on coral pores. The rate of increase in CASS is swifter during the initial strength phase and decelerates during the subsequent stages of strength development. The failure in CASS is experienced primarily within the cement mortar and bonding surface between the cement mortar and aggregate.

10.
Sci Total Environ ; 926: 172133, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38569960

RESUMO

Evaluating the impact of global warming on rice production and greenhouse gas (GHG) emissions is critical for ensuring food security and mitigating the consequences of climate change. Nonetheless, the impacts of warming on crop production, GHG emissions, and microbial mechanisms in the single-cropping rice systems remain unclear. Here, a two-year field experiment was conducted to explore the effects of warming (increased by 2.7-3.0 °C on average) in the rice growing season on crop production and functional microorganisms associated with GHG emissions. Results showed that warming resulted in significant reduction (p < 0.01) in the aboveground biomass and grain yield as well as in grain weight, the number of spikelets per panicle, and the seed-setting rate. However, it caused a significant increase (p < 0.01) in the number of panicles by 15.6 % and 34.9 %, respectively. Furthermore, warming significantly increased (p < 0.01) seasonal methane (CH4) emissions but reduced nitrous oxide (N2O) emissions, particularly in 2022.The relative abundance of genes associated with CH4 metabolism and nitrogen metabolism was increased by 40.7 % and 32.7 %, respectively, in response to warming. Moreover, warming had a positive impact on the abundance of genes related to CH4 production and oxidation processes but did not affect the denitrification processes associated with N2O production. These results showed that warming decreased rice yield and biomass in the single cropping rice system but increased CH4 emissions and global warming potential. Taken together, to address the increasing food demand of a growing population and mitigate the impacts of global warming, it is imperative to duce GHG emissions and enhance crop yields.


Assuntos
Gases de Efeito Estufa , Oryza , Gases de Efeito Estufa/análise , Oryza/metabolismo , Agricultura/métodos , Aquecimento Global , Produção Agrícola , Óxido Nitroso/análise , Metano/análise , Solo , China
11.
Biology (Basel) ; 13(4)2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38666825

RESUMO

The fibrosis process after myocardial infarction (MI) results in a decline in cardiac function due to fibrotic collagen deposition and contrast agents' metabolic disorders, posing a significant challenge to conventional imaging strategies in making heart damage clear in the fibrosis microenvironment. To address this issue, we developed an imaging strategy. Specifically, we pretreated myocardial fibrotic collagen with collagenase I combined with human serum albumin (HSA-C) and subsequently visualized the site of cardiac injury by near-infrared (NIR) fluorescence imaging using an optical contrast agent (CI, CRT-indocyanine green) targeting transferrin receptor 1 peptides (CRT). The key point of this strategy is that pretreatment with HSA-C can reduce background signal interference in the fibrotic tissue while enhancing CI uptake at the heart lesion site, making the boundary between the injured heart tissue and the normal myocardium clearer. Our results showed that compared to that in the untargeted group, the normalized fluorescence intensity of cardiac damage detected by NIR in the targeted group increased 1.28-fold. The normalized fluorescence intensity increased 1.21-fold in the pretreatment group of the targeted groups. These data demonstrate the feasibility of applying pretreated fibrotic collagen and NIR contrast agents targeting TfR1 to identify ferroptosis at sites of cardiac injury, and its clinical value in the management of patients with MI needs further study.

12.
Curr Issues Mol Biol ; 46(4): 2798-2818, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38666905

RESUMO

Iron is essential for many physiological processes, and the dysregulation of its metabolism is implicated in the pathogenesis of various diseases. Recent advances in iron metabolism research have revealed multiple complex pathways critical for maintaining iron homeostasis. Molecular imaging, an interdisciplinary imaging technique, has shown considerable promise in advancing research on iron metabolism. Here, we comprehensively review the multifaceted roles of iron at the cellular and systemic levels (along with the complex regulatory mechanisms of iron metabolism), elucidate appropriate imaging methods, and summarize their utility and fundamental principles in diagnosing and treating diseases related to iron metabolism. Utilizing molecular imaging technology to deeply understand the complexities of iron metabolism and its critical role in physiological and pathological processes offers new possibilities for early disease diagnosis, treatment monitoring, and the development of novel therapies. Despite technological limitations and the need to ensure the biological relevance and clinical applicability of imaging results, molecular imaging technology's potential to reveal the iron metabolic process is unparalleled, providing new insights into the link between iron metabolism abnormalities and various diseases.

13.
Adv Mater ; 36(21): e2313188, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38362813

RESUMO

Immunotherapy represents a revolutionary paradigm in cancer management, showcasing its potential to impede tumor metastasis and recurrence. Nonetheless, challenges including limited therapeutic efficacy and severe immune-related side effects are frequently encountered, especially in solid tumors. Hydrogels, a class of versatile materials featuring well-hydrated structures widely used in biomedicine, offer a promising platform for encapsulating and releasing small molecule drugs, biomacromolecules, and cells in a controlled manner. Immunomodulatory hydrogels present a unique capability for augmenting immune activation and mitigating systemic toxicity through encapsulation of multiple components and localized administration. Notably, hydrogels based on biopolymers have gained significant interest owing to their biocompatibility, environmental friendliness, and ease of production. This review delves into the recent advances in bio-based hydrogels in cancer immunotherapy and synergistic combinatorial approaches, highlighting their diverse applications. It is anticipated that this review will guide the rational design of hydrogels in the field of cancer immunotherapy, fostering clinical translation and ultimately benefiting patients.


Assuntos
Hidrogéis , Imunoterapia , Neoplasias , Hidrogéis/química , Humanos , Imunoterapia/métodos , Neoplasias/terapia , Animais , Materiais Biocompatíveis/química
14.
Bioorg Chem ; 145: 107165, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38367427

RESUMO

Selenium is an essential trace element for most organisms, protecting cells from oxidative damage caused by free radicals and serving as an adjunctive treatment for non-alcoholic fatty liver disease (NAFLD). In this study, We used the lactic acid bacterium Lactobacillus acidophilus HN23 to reduce tetra-valent sodium selenite into particulate matter, and analyzed it through inductively coupled plasma mass spectrometry (ICP-MS), scanning electron microscopy (SEM), X-ray diffraction energy dispersive spectrometry (EDS), and Fourier transform infrared spectroscopy (FTIR). We found that it consisted of selenium nanoparticles (SeNPs) with a mass composition of 65.8 % zero-valent selenium and some polysaccharide and polypeptide compounds, with particle sizes ranging from 60 to 300 nm. We also detected that SeNPs were much less toxic to cells than selenite. We further used free fatty acids (FFA)-induced WRL68 fatty liver cell model to study the therapeutic effect of SeNPs on NAFLD. The results show that SeNPs are more effective than selenite in reducing lipid deposition, increasing mitochondrial membrane potential (MMP) and antioxidant capacity of WRL68 cells, which is attributed to the chemical valence state of selenium and organic composition in SeNPs. In conclusion, SeNPs produced by probiotics L. acidophilus had the potential to alleviate NAFLD by reducing hepatocyte lipid deposition and oxidative damage. This study may open a new avenue for SeNPs drug development to treat NAFLD.


Assuntos
Nanopartículas , Hepatopatia Gordurosa não Alcoólica , Selênio , Humanos , Selênio/farmacologia , Selênio/química , Lactobacillus acidophilus/metabolismo , Nanopartículas/química , Ácido Selenioso/química , Ácido Selenioso/metabolismo , Lipídeos
15.
Ecotoxicol Environ Saf ; 273: 116115, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38377781

RESUMO

Triclosan (TCS) is a widely used synthetic, with broad-spectrum antibacterial properties found in both pharmaceuticals and personal care products. More specifically, it is hepatotoxic in rodents and exhibits differential effects in mice and humans. However, the mechanisms underlying TCS-induced liver toxicity have not been elucidated. This study examined the role of the toll-like receptor 4 (TLR4)/ nuclear factor kappa B (NF-κB)/ nod-like receptor protein 3 (NLRP3) pathway in TCS-exposed liver toxicity by established a long-life TCS-exposed mice liver injury model. The 24 C57BL/6 pregnant mice exposed to TCS (0, 50 and 100 mg/kg) every day during the gestation and nursing period. After weaning, the male mice were left to continue administrate with TCS until 8 weeks of age. Then, mice in each group were sacrificed for investigation. Long-life exposure to TCS resulted in a reduction of body weight in growth mice. TCS exposure caused the increase of serum ALT, AST and ALP. The situation of inflammatory cell infiltration, macrophage recruitment and collagen fiber deposition in TCS-exposed mice liver tissues were performed by histological analysis including hematoxylin-eosin, Masson, Sirius red, and immunohistochemistry staining. Protein expression levels in TLR4/NF-κB/NLRP3 pathway was measured through Western blot, and the NLRP3 inflammasome activation was measured using real-time quantitative PCR (RT-qPCR). The results showed that exposure to TCS elevated TLR4, myeloid differentiation factor 88 (Myd88), TNF receptor associated factor 6 (TRAF6), enhanced NF-κB activation, and affected NLRP3 inflammasome activation in mice liver. Collectively, these findings indicate that long-life exposure to TCS-induced mice by upregulating the TLR4-Myd88-TRAF6 pathway, activating the NF-κB signaling cascade, initiating the NLRP3 inflammasome pathway, and ultimately leading to liver injury, including inflammation, hepatocyte pyroptosis and hepatofibrosis. Henceforth, the TLR4/NF-κB/NLRP3 pathway may now provide a theoretical basis and valuable therapeutic targets for overcoming TCS-induced liver toxicity.


Assuntos
NF-kappa B , Triclosan , Humanos , Camundongos , Masculino , Animais , NF-kappa B/genética , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Inflamassomos/metabolismo , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Triclosan/toxicidade , Fator 88 de Diferenciação Mieloide/genética , Fator 88 de Diferenciação Mieloide/metabolismo , Fator 6 Associado a Receptor de TNF/metabolismo , Camundongos Endogâmicos C57BL , Fígado/metabolismo
16.
J Air Waste Manag Assoc ; 74(3): 192-205, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38329723

RESUMO

Undersized fraction from aged municipal solid waste (UFAMSW), as a kind of soil-like material, has been proved effective in providing a large amount of organic matter and nutrients for soil and plants. The characteristics and effectiveness of heavy metal pollution removal in UFAMSW attracted tremendous research interest from scientists recently. In this study, the heavy metal removal efficiencies and bioavailability of washing on contaminated UFAMSW were evaluated with three washing reagents including ethylene diamine tetra acetic acid (EDTA), citric acid (CA), and humic acid (HA). The effects of chelating agent concentration, pH, and washing time on metal removal were investigated and response surface methodology (RSM) was employed to optimize the washing conditions. The results indicated that the removal efficiencies of Cu, Zn, and Mn could be 53.68%, 52.12%, and 30.63% by EDTA/HA washing and 42.36%, 39.67% and 28.49% by CA/HA washing, respectively. The European Community Bureau of Reference (BCR) sequential extraction was applied to analyze the fraction change of heavy metals in UFAMSW before and after washing, and it was found that chelating agent combined with HA could contribute to the removal of the exchangeable fraction. Physical and chemical properties of UFAMSW were improved to some extent after washing with mixed HA and chelating agent and could achieve the quality standard of landscape gardening soil. Accordingly, the mixture of HA and other chelating agents could be a promising washing process for preparation of landscape gardening soil using UFAMSW.Implications: Our manuscript studies the removal of heavy metals from the contaminated undersized fraction from aged municipal solid waste (UFAMSW). UFAMSW, as a kind of soil-like material, has been proved effective in providing a large amount of organic matter and nutrients for soil and plants however often limited by heavy metal pollution. The UFAMSW used in this experiment was collected after the excavation and screening-sorting of aged refuse from Changshankou Domestic Waste Sanitary Landfill in Wuhan City, Hubei Province, Southern China. This study investigated the effects of EDTA, CA, HA, mixed EDTA/HA, and mixed CA/HA washing on heavy metal removal (Cu, Zn, and Mn), bioavailability of residual heavy metal and properties. The effects of chelating agent concentration, pH, and washing time on metal removal were investigated and then response surface methodology was employed to optimize the washing conditions. The results showed that washing by CA/HA and EDTA/HA, had a higher removal efficiency of heavy metals (Cu, Zn, and Mn) in UFAMSW compared to single HA. Meanwhile, HA has a higher removal for exchangeable fraction of heavy metals, the exchangeable concentration of Cu, Zn, and Mn in CA/HA and EDTA/HA washed UFAMSW were lower compared with UFAMSW washed by single CA and EDTA. Thus, mixing HA with EDTA or CA makes a less risk to environmental and the removal efficiency is acceptable. Additionally, CA/HA and EDTA/HA washing tend to improve soil physicochemical properties and soil fertility. Thus, mixing HA with different washing agent are potential methods for preparation of landscape gardening soil using UFAMSW.


Assuntos
Metais Pesados , Poluentes do Solo , Ácido Edético/química , Substâncias Húmicas , Solo/química , Ácido Acético , Ácido Cítrico/química , Jardinagem , Resíduos Sólidos , Poluentes do Solo/análise , Quelantes/química , Metais Pesados/análise
17.
Pharmacol Res ; 200: 107052, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38181857

RESUMO

BACKGROUND: The efficacy and safety of Qingda granule (QDG) in managing blood pressure (BP) among grade 1 hypertensive patients with low-moderate risk remain uncertain. METHODS: In the randomized, double-blind, double dummy, non-inferiority and multicenter trial, 552 patients with grade 1 hypertension at low-moderate risk were assigned at a ratio of 1:1 to receive either QDG or valsartan for 4 weeks, followed up by a subsequent 4 weeks. RESULTS: Post-treatment, clinic systolic/diastolic BPs (SBP/DBP) were reduced by a mean change of 9.18/4.04 mm Hg in the QDG group and 9.85/5.05 mm Hg in the valsartan group (SBP P = 0.47, DBP P = 0.16). Similarly, 24-hour, daytime and nighttime BPs were proportional in both groups (P > 0.05) after 4 weeks treatment. After discontinuing medications for 4 weeks, the mean reduction of clinic SBP/DBP were 0.29/0.57 mm Hg in the QDG group compared to -1.59/-0.48 mm Hg in the valsartan group (SBP P = 0.04, DBP P = 0.04). Simultaneously, the 24-hour SBP/DBP were reduced by 0.9/0.31 mm Hg in the QDG group and -1.66/-1.08 mm Hg in the valsartan group (SBP P = 0.006, DBP P = 0.02). And similar results were observed regarding the outcomes of daytime and nighttime BPs. There was no difference in occurrence of adverse events between two groups (P > 0.05). CONCLUSION: QDG proves to be efficacious for grade 1 hypertension at a low-to-medium risk, even after discontinuation of the medication for 4 weeks. These findings provide a promising option for managing grade 1 hypertension and suggest the potential for maintaining stable BP through intermittent administration of QDG. TRIAL REGISTRATION: ChiCTR2000033890.


Assuntos
Anti-Hipertensivos , Medicamentos de Ervas Chinesas , Hipertensão , Humanos , Anti-Hipertensivos/efeitos adversos , Pressão Sanguínea , China , Método Duplo-Cego , Tetrazóis/efeitos adversos , Valsartana/efeitos adversos
18.
ACS Sens ; 8(12): 4728-4736, 2023 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-38085692

RESUMO

Breath hydrogen (H2) and methane (CH4) monitoring play an important role in the diagnosis of gastrointestinal disorders, such as lactose intolerance and small intestinal bacterial overgrowth (SIBO). In this paper, the photoacoustic spectroscopy method is used for H2 gas and CH4 gas detection. We present a novel approach for H2 gas concentration measurement, which is the linear relationship between the resonant frequency of breath carbon dioxide (CO2) and the H2 concentration in a resonant photoacoustic cell. Experimental results show that the minimum detectable limits of H2, CH4, and CO2 are calculated to be 8.86, 0.56, and 145.14 ppm, respectively, which can meet the requirements of breath diagnosis.


Assuntos
Líquidos Corporais , Intolerância à Lactose , Humanos , Dióxido de Carbono , Intolerância à Lactose/diagnóstico , Testes Respiratórios/métodos , Análise Espectral
19.
Front Public Health ; 11: 1183200, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37908690

RESUMO

Background: It remains controversial regarding the association between weight change and cardiovascular disease risk in older adults (aged ≥60 years). This study aimed to evaluate the association between weight change and the predicted 10-year atherosclerotic cardiovascular disease (ASCVD) risks in older adults. Methods: This study used data from the National Health and Nutrition Examination Survey (NHANES). Older adults aged 60-79 years who were free of self-reported ASCVD at the time of the NHANES interview were included. Data were collected from January 1999 to December 2018 and analyzed in March 2022. We focused on the associations between weight change and the 10-year ASCVD risks with the percentage change in weight during short-term (1 year) and long-term (10 years), which categorized as moderate to high weight loss (≥10%), small weight loss (5.1-9.9%), stable weight (±5%), small weight gain (5.1-9.9%), and moderate to high weight gain (≥10%). Results: The number of participants was 1,867 (mean age 67.49 years; 42.10% female) for the long-term interval (10 years) in our analysis, and 1894 for the short-term interval (1 years). We only observed an inverse association between long-term weight loss and the 10-year ASCVD risk in fully adjusted model (loss ≥ 10%: ß = 2.52, 95%CI = 0.98, 4.05; loss 5.1% ~ 9.9%: ß = 2.99, 95% CI = 1.30, 4.68), but all intervals of weight gain ≥5% were not significant associated with higher risk than stable weight. However, in the subgroup analyses, the association between long-term weight loss and the 10-year ASCVD risk was not significant in old-old (aged 75-79), obesity (BMI ≥ 35 kg/m2), intentional weight loss, moderate physical activity and diabetics. Conclusion: Older adults (aged 60-79 years) with weight loss >5% over the past 10 years have excess predicted 10-year ASCVD risk. Our study supports the benefits of stable weight in promoting cardiovascular health in older adults.


Assuntos
Aterosclerose , Doenças Cardiovasculares , Humanos , Feminino , Idoso , Masculino , Doenças Cardiovasculares/epidemiologia , Fatores de Risco , Inquéritos Nutricionais , Medição de Risco , Aterosclerose/epidemiologia , Aumento de Peso , Redução de Peso
20.
BMC Plant Biol ; 23(1): 547, 2023 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-37936114

RESUMO

BACKGROUND: The intensified global warming during grain filling deteriorated rice quality, in particular increasing the frequency of chalky grains which markedly impact market value. The formation of rice quality is a complex process influenced by multiple genes, proteins and physiological metabolic processes. Proteins responsive to stimulus can adjust the ability of plants to respond to unfavorable environments, which may be an important protein involved in the regulation of quality formation under elevated temperature. However, relatively few studies have hindered our further understanding of rice quality formation under elevated temperature. RESULTS: We conducted the actual field elevated temperature experiment and performed proteomic analysis of rice grains at the early stage of grain filling. Starting with the response to stimulus in GO annotation, 22 key proteins responsive to stimulus were identified in the regulation of grain filling and response to elevated temperature. Among the proteins responsive to stimulus, during grain filling, an increased abundance of signal transduction and other stress response proteins, a decreased abundance of reactive oxygen species-related proteins, and an increased accumulation of storage substance metabolism proteins consistently contributed to grain filling. However, the abundance of probable indole-3-acetic acid-amido synthetase GH3.4, probable indole-3-acetic acid-amido synthetase GH3.8 and CBL-interacting protein kinase 9 belonged to signal transduction were inhibited under elevated temperature. In the reactive oxygen species-related protein, elevated temperature increased the accumulation of cationic peroxidase SPC4 and persulfide dioxygenase ETHE1 homolog to maintain normal physiological homeostasis. The increased abundance of alpha-amylase isozyme 3E and seed allergy protein RA5 was related to the storage substance metabolism, which regulated starch and protein accumulation under elevated temperature. CONCLUSION: Auxin synthesis and calcium signal associated with signal transduction, other stress responses, protein transport and modification, and reactive oxygen species-related proteins may be key proteins responsive to stimulus in response to elevated temperature. Alpha-amylase isozyme 3E and seed allergy protein RA5 may be the key proteins to regulate grain storage substance accumulation and further influence quality under elevated temperature. This study enriched the regulatory factors involved in the response to elevated temperature and provided a new idea for a better understanding of grain response to temperature.


Assuntos
Hipersensibilidade , Oryza , Oryza/genética , Temperatura , Proteômica , Espécies Reativas de Oxigênio/metabolismo , Isoenzimas/metabolismo , Grão Comestível/metabolismo , Proteínas de Choque Térmico/metabolismo , alfa-Amilases/metabolismo , Ligases/metabolismo , Hipersensibilidade/metabolismo
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