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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.
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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.
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Antihipertensivos , Medicamentos Herbarios Chinos , Hipertensión , Humanos , Antihipertensivos/efectos adversos , Presión Sanguínea , China , Método Doble Ciego , Tetrazoles/efectos adversos , Valsartán/efectos adversosRESUMEN
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.
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Nanopartículas , Enfermedad del Hígado Graso no Alcohólico , Selenio , Humanos , Selenio/farmacología , Selenio/química , Lactobacillus acidophilus/metabolismo , Nanopartículas/química , Ácido Selenioso/química , Ácido Selenioso/metabolismo , LípidosRESUMEN
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 100â¯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.
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FN-kappa B , Triclosán , Humanos , Ratones , Masculino , Animales , FN-kappa B/genética , FN-kappa B/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Inflamasomas/metabolismo , Receptor Toll-Like 4/genética , Receptor Toll-Like 4/metabolismo , Triclosán/toxicidad , Factor 88 de Diferenciación Mieloide/genética , Factor 88 de Diferenciación Mieloide/metabolismo , Factor 6 Asociado a Receptor de TNF/metabolismo , Ratones Endogámicos C57BL , Hígado/metabolismoRESUMEN
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 0â¯mg/kg (control) or 50â¯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 0â¯mg/kg (control) or 3â¯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.
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Trastorno por Déficit de Atención con Hiperactividad , Dopamina , Corteza Prefrontal , Efectos Tardíos de la Exposición Prenatal , Triclosán , Animales , Triclosán/toxicidad , Corteza Prefrontal/efectos de los fármacos , Corteza Prefrontal/metabolismo , Trastorno por Déficit de Atención con Hiperactividad/inducido químicamente , Femenino , Ratas , Embarazo , Masculino , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Dopamina/metabolismo , Ratas Sprague-Dawley , Conducta Animal/efectos de los fármacos , Clorhidrato de Atomoxetina , HumanosRESUMEN
Immunotherapies have shown high clinical success, however, the therapeutical efficacy is largely restrained by insufficient immune activation and an immunosuppressive microenvironment. Herein, we report tumor microenvironment (TME)-responsive manganese-enriched zinc peroxide nanoparticles (MONPs) for synergistic cancer immunotherapy by inducing the immunogenic death (ICD) of cancer cells and activating the stimulator of the interferon gene (STING) pathway. MONPs especially disassociate upon exposure to acidic tumor tissue and in situ generate â¢OH for the ICD effect. Moreover, Mn2+ activated the STING and synergistically induced the secretion of type I interferon and inflammatory cytokines for specific T cell responses. Meanwhile, MONPs relieved the immunosuppression of TME through decreasing Tregs and polarizing M2 macrophages to the M1 type to unleash a cascade adaptive immune response. In combination with the anti-PD-1 antibody, MONPs showed superior efficacy in inhibiting tumor growth and preventing lung metastasis. Our study demonstrates the feasibility of functional nanoparticles to amplify STING innate stimulation, showing a prominent strategy for cancer immunotherapy.
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Neoplasias Pulmonares , Nanopartículas , Neoplasias , Humanos , Manganeso/uso terapéutico , Inmunoterapia , Nanopartículas/uso terapéutico , Microambiente Tumoral , Peróxidos , Zinc , Neoplasias/tratamiento farmacológicoRESUMEN
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.
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Hipersensibilidad , Oryza , Oryza/genética , Temperatura , Proteómica , Especies Reactivas de Oxígeno/metabolismo , Isoenzimas/metabolismo , Grano Comestible/metabolismo , Proteínas de Choque Térmico/metabolismo , alfa-Amilasas/metabolismo , Ligasas/metabolismo , Hipersensibilidad/metabolismoRESUMEN
Hydrogenolysis is an effective method for converting polyolefins into high-value chemicals. For the supported catalysts commonly used, the size of active metals is of great importance. In this study, it is discovered that the activity of CeO2 -supported Ru single atom, nanocluster, and nanoparticle catalysts shows a volcanic trend in low-density polyethylene (LDPE) hydrogenolysis. Compared with CeO2 supported Ru single atoms and nanoparticles, CeO2 -supported Ru nanoclusters possess the highest conversion efficiency, as well as the best selectivity toward liquid alkanes. Through comprehensive investigations, the metal-support interactions (MSI) and hydrogen spillover effect are revealed as the two key factors in the reaction. On the one hand, the MSI is strongly related to the Ru surface states and the more electronegative Ru centers are beneficial to the activation of CH and CC bonds. On the other hand, the hydrogen spillover capability directly affects the affinity of catalysts and active H atoms, and increasing this affinity is advantageous to the hydrogenation of alkane species. Decreasing the Ru sizes can promote the MSI, but it can also reduce the hydrogen spillover effect. Therefore, only when the two effects achieve a balance, as is the case in CeO2 -supported Ru nanoclusters, can the hydrogenolysis activity be promoted to the optimal value.
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Insecticides have been widely used for the control of insect pests that have a significant impact on agriculture and human health. A better understanding of insecticide targets is needed for effective insecticide design and resistance management. Pymetrozine, afidopyropen and flonicamid are reported to target on proteins that located on insect chordotonal organs, resulting in the disruption of insect coordination and the inhibition of feeding. In this study, we systematically examined the susceptibility of six Drosophila melanogaster mutants (five transient receptor potential channels and one mechanoreceptor) to three commercially used insecticides, in order to identify the receptor subunits critical to the insect's response to insecticides. Our results showed that iav1, nan36aand wtrw1 mutants exhibited significantly reduced susceptibility to pymetrozine and afidopyropen, but not to flonicamid. The number of eggs produced by the three mutant females were significantly less than that of the w1118 strain. Meanwhile, the longevity of all male mutants and females of nan36a and wtrw1 mutants was significantly shorter than that of the w1118 strain as the control. However, we observed no gravitaxis defects in wtrw1 mutants and the anti-gravitaxis of wtrw1 mutants was abolished by pymetrozine. Behavioral assays using thermogenetic tools further confirmed the bioassay results and supported the idea that Nan as a TRPV subfamily member located in Drosophila chordotonal neurons, acting as a target of pymetrozine, which interferes with Drosophila and causes motor deficits with gravitaxis defects. Taken together, this study elucidates the interactions of pymetrozine and afidopyropen with TRPV channels, Nan and Iav, and TRPA channel, Wtrw. Our research provides another evidence that pymetrozine and afidopyropen might target on nan, iav and wtrw channels and provides insights into the development of sustainable pest management strategies.
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Drosophila melanogaster , Insecticidas , Animales , Femenino , Humanos , Drosophila melanogaster/genética , Insecticidas/farmacología , Genética Inversa , Drosophila/genéticaRESUMEN
In this article, a miniaturized antenna is proposed for 4G/5G multiple input, multiple output (MIMO) applications for smartphones. The proposed antenna is composed of an inverted L-shaped antenna with decoupled elements to cover 4G (2000-2600 MHz), and a planar inverted-F antenna (PIFA) with a J-slot to cover 5G (3400-3600 MHz and 4800-5000 MHz). Furthermore, to achieve the purposes of miniaturization and decoupling, the structure adopts a feeding stub, shorting stub, and outstanding floor, additionally adding the slot to the PIFA, to generate additional frequency bands. Due to the advantages such as multiband operation, MIMO configuration for 5G communications, high isolation, and a compact structure, the proposed antenna design is attractive for 4G/5G smartphones. The antenna array is printed on an FR4 dielectric board, measuring 140 × 70 × 0.8 mm3, with the 4G antenna located on a top 15 mm-long headroom.
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Comunicación , Teléfono Inteligente , Miniaturización , Orientación EspacialRESUMEN
Materials with a quasi-one-dimensional stripy magnetic order often exhibit low crystal and magnetic symmetries, thus allowing the presence of various energy coupling terms and giving rise to macroscopic interplay between spin, charge, and phonon. In this work, we performed optical, electrical and magnetic characterizations combined with first-principles calculations on a van der Waals antiferromagnetic insulator chromium oxychloride (CrOCl). We detected the subtle phase transition behaviors of exfoliated CrOCl under varying temperature and magnetic field and clarified its controversial spin structures. We found that the antiferromagnetism and its air stability persist down to few-layer samples, making it a promising candidate for future 2D spintronic devices. Additionally, we verified the magnetoelastic coupling effect in CrOCl, allowing for the potential manipulation of the magnetic states via electric field or strain. These virtues of CrOCl provide us with an ideal platform for fundamental research on spin-charge, spin-phonon coupling, and spin-interactions.
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MnBi_{2}Te_{4}, an intrinsic magnetic topological insulator, has shown layer-number-correlated magnetic and topological phases. More interestingly, in the isostructural material MnSb_{2}Te_{4}, the antiferromagnetic (AFM) and ferromagnetic (FM) states have been both observed in the bulk counterparts, which are also predicted to be topologically nontrivial. Revealing the layer-number-dependent magnetic properties of MnSb_{2}Te_{4} down to a single septuple layer (SL) is of great significance for exploring the topological phenomena. However, this is still elusive. Here, using the polar reflective magnetic circular dichroism spectroscopy, both the A-type AFM and FM behaviors are observed and comprehensively studied in MnSb_{2}Te_{4} down to a single SL limit. In A-type AFM MnSb_{2}Te_{4} flakes, an obvious odd-even layer-number effect is observed. An additional surface spin-flop (SSF) transition occurs in even-SL flakes with the number of layers larger than 2. With the AFM linear-chain model, we identify that the even-SL flakes stabilize in a collinear state between the SSF transition and the spin-flop transition due to their appropriate energy ratio between the magnetic-field-scale anisotropy and interlayer interaction. In FM MnSb_{2}Te_{4} flakes, we observe very different magnetic behaviors with an abrupt spin-flipping transition and very small saturation fields, indicating a weakened interlayer interaction. By revealing the rich magnetic states of few-SL MnSb_{2}Te_{4} on the parameter space of the number of layers, external magnetic field, and temperature, our findings pave the way for further quantum transport studies of few-SL MnSb_{2}Te_{4}.
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OBJECTIVE: Lacosamide (LCM), is a third-generation antiseizure medicine, with limited clinical evidence for use in pediatric populations. We aimed to evaluate evidence for the efficacy and safety of LCM in pediatric patients with epilepsy. METHODS: A systematic review was performed using literature published from inception to February 2022 identified in MEDLINE, Embase, Cochrane Library, and four Chinese databases. Efficacy and safety outcome data were collected, and a meta-analysis was performed. RESULT: Twenty-one studies involving 1230 pediatric patients were included. The median percent reduction in seizure frequency per 28â¯days from baseline to maintenance was 33.1% (95% confidence interval [CI] 22.7%, 43.5%). After 6â¯months of treatment, the 50%, 75%, and 100% responder rates were 53.3% (95% CI 40.7%, 65.9%), 28.3% (95% CI 20.8%, 35.8%), and 20.4% (95% CI 12.6%, 28.2%), respectively. After 12â¯months of treatment, the 50%, 75%, and 100% responder rates were 42.0% (95% CI 29.5%, 54.5%), 19.5% (95% CI 11.1%, 27.8%), and 15.2% (95% CI 6.6%, 23.8%), respectively. The most common adverse events (AEs) were drowsiness (15.0%), dizziness (9.9%), and somnolence (8.3%). CONCLUSION: Lacosamide is generally effective and well tolerated to use in children with epilepsy. However, further research with high-quality data and long-term follow-up of LCM use in pediatric populations is needed.
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Epilepsias Parciales , Epilepsia , Anticonvulsivantes , Niño , Humanos , Lacosamida , Somnolencia , Resultado del TratamientoRESUMEN
We collected 682 topsoil samples (0-20cm) from agricultural lands of Luhe County in East China, and analyzed the spatial distribution patterns and potential sources of four major heavy metals. High Pb and Cr were mainly in the southeast adjacent to the Yangtze River, and Cd were characterized by an increasing trend from northwest to southeast, while high Hg mainly occurred in the areas near downtown. Spatially-continuous sources dominated the soil heavy metal concentrations. Contributions of spatially-continuous natural source (soil parent material) to Cr and Cd were 97.0% and 77.7%, respectively, whereas contributions of spatially-continuous anthropogenic source such as diffuse pollution to Pb and Hg were 75.7% and 86.7%, respectively. The distance to factories was the most influential anthropogenic factor for localized anomaly patterns of Pb, Cd, and Cr, while the intensive agricultural land uses associated with the rapid urban expansion were particularly relevant to the anomaly patterns of Hg.
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Metales Pesados , Contaminantes del Suelo , China , Monitoreo del Ambiente , Metales Pesados/análisis , Medición de Riesgo , Suelo , Contaminantes del Suelo/análisisRESUMEN
Ferromagnetic order in two-dimensional (2D) van der Waals crystals has been attracting much attention recently. Remarkably, room temperature metallic ferromagnetism is realized in 2D Fe3GeTe2. Here we design a monolayer (ML) Fe3GeTe2 spin-valve device by attaching two ends to ferromagnetic electrodes and applying a magnetic field to these ferromagnetic electrodes. We investigate the spin-involved transport characteristics of such a spin valve by using ab initio quantum transport simulation. A high magnetoresistance of â¼390% is obtained and significantly increased to 450-510% after the gates are introduced. The magnetoresistance of the ML Fe3GeTe2 spin valve is insensitive to the strain modulation. Our study provides a potential option for magnetic storage applications and will motivate further studies in spintronics based on this class of materials.
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Fuzhuan brick tea (FBT) is traditionally consumed by the ethnic group in the border region of northwest China. The unique yellow fungal (Eurotium cristatum) growth phase is considered to be the key process point in the manufacture of the brick tea. The fungi from FBT are not only strongly correlated to the quality of brick tea, but also have the potential function of preventing obesity. The water extract of fungi (100 µg/mL) can significantly inhibit fat deposition in 3T3-L1 adipocyte and Caenorhabditis elegans. Furthermore, the inhibition of 3T3-L1 adipocyte formation was not due to the suppression on cell viability.
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Adipocitos/efectos de los fármacos , Camellia sinensis/química , Hongos/química , Té/química , Células 3T3 , Animales , Caenorhabditis elegans/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , China , Fermentación , Ratones , Obesidad/prevención & control , Agua/químicaRESUMEN
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.
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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.
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Microglía , Enfermedades Neuroinflamatorias , Piruvato Quinasa , Factor de Transcripción STAT3 , Triclosán , Animales , Triclosán/toxicidad , Ratones , Microglía/efectos de los fármacos , Piruvato Quinasa/metabolismo , Factor de Transcripción STAT3/metabolismo , Fosforilación , Enfermedades Neuroinflamatorias/inducido químicamente , Antiinfecciosos Locales/toxicidad , MasculinoRESUMEN
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.
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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.