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ABSTRACT: Current iron overload therapeutics have inherent drawbacks including perpetuated low hepcidin. Here, we unveiled that lactate, a potent hepcidin agonist, effectively reduced serum and hepatic iron levels in mouse models of iron overload with an improved erythropoiesis in ß-thalassemic mice.
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Sobrecarga de Ferro , Talassemia beta , Camundongos , Animais , Hepcidinas , Modelos Animais de Doenças , Ácido Láctico , Talassemia beta/tratamento farmacológico , Sobrecarga de Ferro/tratamento farmacológicoRESUMO
Microglial polarization and associated inflammatory activity are the key mediators of depression pathogenesis. The natural Smilax glabra rhizomilax derivative engeletin has been reported to exhibit robust anti-inflammatory activity, but no studies to date have examined the mechanisms through which it can treat depressive symptoms. We showed that treatment for 21 days with engeletin significantly alleviated depressive-like behaviours in chronic stress social defeat stress (CSDS) model mice. T1-weighted imaging (T1WI), T2-weighted imaging (T2WI) imaging revealed no significant differences between groups, but the bilateral prefrontal cortex of CSDS mice exhibited significant increases in apparent diffusion coefficient and T2 values relative to normal control mice, with a corresponding reduction in fractional anisotropy, while engeletin reversed all of these changes. CSDS resulted in higher levels of IL-1ß, IL-6, and TNF-a production, enhanced microglial activation, and greater M1 polarization with a concomitant decrease in M2 polarization in the mPFC, whereas engeletin treatment effectively abrogated these CSDS-related pathological changes. Engeletin was further found to suppress the LCN2/C-X-C motif chemokine ligand 10 (CXCL10) signalling axis such that adeno-associated virus-induced LCN2 overexpression ablated the antidepressant effects of engeletin and reversed its beneficial effects on the M1/M2 polarization of microglia. In conclusion, engeletin can alleviate CSDS-induced depressive-like behaviours by regulating the LCN2/CXCL10 pathway and thereby altering the polarization of microglia. These data suggest that the antidepressant effects of engeletin are correlated with the polarization of microglia, highlighting a potential avenue for future design of antidepressant strategies that specifically target the microglia.
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Antidepressivos , Flavonóis , Glicosídeos , Microglia , Camundongos , Animais , Microglia/metabolismo , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Depressão/tratamento farmacológico , Depressão/etiologia , Transdução de SinaisRESUMO
Hair follicle stem cells (HFSCs) are maintained in a quiescent state until activated to grow, but the mechanisms that reactivate the quiescent HFSC reservoir are unclear. Here, we find that loss of Sirt7 in mice impedes hair follicle life-cycle transition from telogen to anagen phase, resulting in delay of hair growth. Conversely, Sirt7 overexpression during telogen phase facilitated HSFC anagen entry and accelerated hair growth. Mechanistically, Sirt7 is upregulated in HFSCs during the telogen-to-anagen transition, and HFSC-specific Sirt7 knockout mice (Sirt7f/f ;K15-Cre) exhibit a similar hair growth delay. At the molecular level, Sirt7 interacts with and deacetylates the transcriptional regulator Nfatc1 at K612, causing PA28γ-dependent proteasomal degradation to terminate Nfatc1-mediated telogen quiescence and boost anagen entry. Cyclosporin A, a potent calcineurin inhibitor, suppresses nuclear retention of Nfatc1, abrogates hair follicle cycle delay, and promotes hair growth in Sirt7-/- mice. Furthermore, Sirt7 is downregulated in aged HFSCs, and exogenous Sirt7 overexpression promotes hair growth in aged animals. These data reveal that Sirt7 activates HFSCs by destabilizing Nfatc1 to ensure hair follicle cycle initiation.
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Folículo Piloso/enzimologia , Sirtuínas/metabolismo , Células-Tronco/enzimologia , Envelhecimento/genética , Envelhecimento/metabolismo , Animais , Senescência Celular/efeitos dos fármacos , Ciclosporina/farmacologia , Camundongos , Camundongos Knockout , Fatores de Transcrição NFATC/genética , Fatores de Transcrição NFATC/metabolismo , Sirtuínas/genéticaRESUMO
Nitrogen dioxide (NO2) hydrolysis in deliquesced aerosol particles forms nitrous acid and nitrate and thus impacts air quality, climate, and the nitrogen cycle. Traditionally, it is considered to proceed far too slowly in the atmosphere. However, the significance of this process is highly uncertain because kinetic studies have only been made in dilute aqueous solutions but not under high ionic strength conditions of the aerosol particles. Here, we use laboratory experiments, air quality models, and field measurements to examine the effect of the ionic strength on the reaction kinetics of NO2 hydrolysis. We find that high ionic strengths (I) enhance the reaction rate constants (kI) by more than an order of magnitude compared to that at infinite dilution (kI=0), yielding log10(kI/kI=0) = 0.04I or rate enhancement factor = 100.04I. A state-of-the-art air quality model shows that the enhanced NO2 hydrolysis reduces the negative bias in the simulated concentrations of nitrous acid by 28% on average when compared to field observations over the North China Plain. Rapid NO2 hydrolysis also enhances the levels of nitrous acid in other polluted regions such as North India and further promotes atmospheric oxidation capacity. This study highlights the need to evaluate various reaction kinetics of atmospheric aerosols with high ionic strengths.
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Aerossóis , Aerossóis/química , Hidrólise , Concentração Osmolar , Dióxido de Nitrogênio/química , Cinética , Atmosfera/química , Poluentes Atmosféricos/químicaRESUMO
BACKGROUND: Chronic wasting disease (CWD) is a prion disease of captive and free-ranging cervids. Currently, a definitive diagnosis of CWD relies on immunohistochemistry detection of PrPSc in the obex and retropharyngeal lymph node (RPLN) of the affected cervids. For high-throughput screening of CWD in wild cervids, RPLN samples are tested by ELISA followed by IHC confirmation of positive results. Recently, real-time quacking-induced conversion (RT-QuIC) has been used to detect CWD positivity in various types of samples. To develop a blood RT-QuIC assay suitable for CWD diagnosis, this study evaluated the assay sensitivity and specificity with and without ASR1-based preanalytical enrichment and NaI as the main ionic component in assay buffer. RESULTS: A total of 23 platelet samples derived from CWD-positive deer (ELISA + /IHC +) and 30 platelet samples from CWD-negative (ELISA-) deer were tested. The diagnostic sensitivity was 43.48% (NaCl), 65.22% (NaI), 60.87% (NaCl-ASR1) or 82.61% (NaI-ASR1). The diagnostic specificity was 96.67% (NaCl), 100% (NaI), 100% (NaCl-ASR1), or 96.67% (NaI-ASR1). The probability of detecting CWD prion in platelet samples derived from CWD-positive deer was 0.924 (95% CRI: 0.714, 0.989) under NaI-ASR1 experimental condition and 0.530 (95% CRI: 0.156, 0.890) under NaCl alone condition. The rate of amyloid formation (RFA) was greatest under the NaI-ASR1 condition at 10-2 (0.01491, 95% CRI: 0.00675, 0.03384) and 10-3 (0.00629, 95% CRI: 0.00283, 0.01410) sample dilution levels. CONCLUSIONS: Incorporation of ASR1-based preanalytical enrichment and NaI as the main ionic component significantly improved the sensitivity of CWD RT-QuIC on deer platelet samples. Blood test by the improved RT-QuIC assay may be used for antemortem and postmortem diagnosis of CWD.
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Plaquetas , Cervos , Sensibilidade e Especificidade , Doença de Emaciação Crônica , Animais , Cervos/sangue , Doença de Emaciação Crônica/diagnóstico , Doença de Emaciação Crônica/sangue , Plaquetas/química , Ensaio de Imunoadsorção Enzimática/veterinária , Príons/sangueRESUMO
BACKGROUND: Members of the nucleotide-binding oligomerization domain, leucine rich repeat and pyrin domain containing (NLRP) family regulate various physiological and pathological processes. However, none have been shown to regulate actin cap formation or spindle translocation during the asymmetric division of oocyte meiosis I. NLRP4E has been reported as a candidate protein in female fertility, but its function is unknown. METHODS: Immunofluorescence, reverse transcription polymerase chain reaction (RT-PCR), and western blotting were employed to examine the localization and expression levels of NLRP4E and related proteins in mouse oocytes. small interfering RNA (siRNA) and antibody transfection were used to knock down NLRP4E and other proteins. Immunoprecipitation (IP)-mass spectrometry was used to identify the potential proteins interacting with NLRP4E. Coimmunoprecipitation (Co-IP) was used to verify the protein interactions. Wild type (WT) or mutant NLRP4E messenger RNA (mRNA) was injected into oocytes for rescue experiments. In vitro phosphorylation was employed to examine the activation of steroid receptor coactivator (SRC) by NLRP4E. RESULTS: NLRP4E was more predominant within oocytes compared with other NLRP4 members. NLRP4E knockdown significantly inhibited actin cap formation and spindle translocation toward the cap region, resulting in the failure of polar body extrusion at the end of meiosis I. Mechanistically, GRIN1, and GANO1 activated NLRP4E by phosphorylation at Ser429 and Thr430; p-NLRP4E is translocated and is accumulated in the actin cap region during spindle translocation. Next, we found that p-NLRP4E directly phosphorylated SRC at Tyr418, while p-SRC negatively regulated p-CDC42-S71, an inactive form of CDC42 that promotes actin cap formation and spindle translocation in the GTP-bound form. CONCLUSIONS: NLRP4E activated by GRIN1 and GANO1 regulates actin cap formation and spindle translocation toward the cap region through upregulation of p-SRC-Tyr418 and downregulation of p-CDC42-S71 during meiosis I.
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Actinas , Meiose , Oócitos , Proteína cdc42 de Ligação ao GTP , Animais , Oócitos/metabolismo , Camundongos , Feminino , Actinas/metabolismo , Actinas/genética , Proteína cdc42 de Ligação ao GTP/metabolismo , Proteína cdc42 de Ligação ao GTP/genética , Fosforilação , Fuso Acromático/metabolismoRESUMO
Recent evidence has pinpointed a key role of the microbiome in human respiratory health and disease. However, significant knowledge gaps still exist regarding the connection between bacterial communities and adverse effects caused by particulate matters (PMs). Here, we characterized the bacterial microbiome along different airway sites in occupational pneumoconiosis (OP) patients. The sequencing data revealed that OP patients exhibited distinct dysbiosis in the composition and function of the respiratory microbiota. To different extents, there was an overall increase in the colonization of microbiota, such as Streptococcus, implying a possible intrusion pathway provided by exogenous PMs. Compared to those of healthy subjects, unhealthy living habits (i.e., smoking) had a greater impact on microbiome changes in OP patients. Importantly, the associations between the bacterial community and disease indicators indicated that specific bacterial species, including Prevotella, Actinobacillus, and Leptotrichia, might be surrogate markers of OP disease progression. Collectively, our results highlighted the potential participation of the bacterial microbiota in the pathogenesis of respiratory diseases and helped in the discovery of microbiome-based diagnostics for PM-induced disorders.
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As a dominating air pollutant, atmospheric fine particulate matter within 2.5 µm in diameter (PM2.5) has attracted increasing attention from the researchers all over the world, which will lead to various adverse effects on the central nervous system (CNS), yet the potential mechanism is unclear. In this study, the microglia (BV2 cell line) were exposed to different concentrations of PM2.5 (5, 10 and 20⯵g/cm2) for 24â¯h. It was found that PM2.5 could result in adverse effects on microglia such as decreased cell viability, structural damage and even cell death. And it was reported that long non-coding RNAs (lncRNAs) could participate in multitudinous neurological diseases. Therefore, the microarray analysis was conducted in order to disclose the underlying neurotoxicity mechanism of PM2.5 by ascertaining the differentially expressed lncRNAs (DElncRNAs). The consequences indicated that the DElncRNAs were enriched in various biological pathways, including ferroptosis, IL-17 signaling pathway and NOD-like receptor signaling pathway. Moreover, the cis- and trans-regulated mRNAs by DElncRNAs as well as the corresponding transcriptional factors (TFs) were observed, such as CEBPA, MYC, MEIS1 and KLF4. In summary, our study supplies some candidate libraries and potential preventive target against PM2.5-induced toxicity through targeting lncRNAs. Furthermore, the post-transcriptional regulation will contribute to the future research on PM2.5-induced neurotoxicity.
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Poluentes Atmosféricos , RNA Longo não Codificante , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Microglia/metabolismo , Material Particulado/toxicidade , Material Particulado/metabolismo , Poluentes Atmosféricos/toxicidade , Análise em MicrossériesRESUMO
Adrenal vein sampling is required for the staging diagnosis of primary aldosteronism, and the frames in which the adrenal veins are presented are called key frames. Currently, the selection of key frames relies on the doctor's visual judgement which is time-consuming and laborious. This study proposes a key frame recognition algorithm based on deep learning. Firstly, wavelet denoising and multi-scale vessel-enhanced filtering are used to preserve the morphological features of the adrenal veins. Furthermore, by incorporating the self-attention mechanism, an improved recognition model called ResNet50-SA is obtained. Compared with commonly used transfer learning, the new model achieves 97.11% in accuracy, precision, recall, F1, and AUC, which is superior to other models and can help clinicians quickly identify key frames in adrenal veins.
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Aprendizado Profundo , Raios X , RadiografiaRESUMO
Major depressive disorder (MDD) is a severe mental disorder associated with high rates of morbidity and mortality. Current first-line pharmacotherapies for MDD are based on enhancement of monoaminergic neurotransmission, but these antidepressants are still insufficient and produce significant side-effects. Consequently, the development of novel antidepressants and therapeutic targets is desired. Engeletin, a natural Smilax glabra rhizomilax derivative, is a compound with proven efficacy in treating ischemic stroke, yet its therapeutic effects and mechanisms for depression remain unexplored. The effects of engeletin were assessed in the forced swimming test (FST) and tail suspension test (TST) in mice. Engeletin was also investigated in the chronic restraint stress (CRS) mouse model of depression with fluoxetine (FLX) as the positive control. Changes in prefrontal cortex (PFC) spine density, synaptic plasticity-linked protein expressions and the brain-derived neurotrophic factor (BDNF)-tyrosine kinase B (TrkB)- mammalian target of rapamycin complex 1 (mTORC1) signalling pathway after chronic stress and engeletin treatment were then investigated. The TrkB and mTORC1 selective inhibitors, ANA-12 and rapamycin, respectively, were utilized to assess the engeletin's antidepressive mechanisms. Our data shows that engeletin exhibited antidepressant-like activity in the FST and TST in mice without affecting locomotor activity. Furthermore, it exhibited efficiency against the depression of CRS model. Moreover, it enhanced the BDNF-TrkB-mTORC1 pathway in the PFC during CRS and altered the reduction in dendritic spine density and levels of synaptic plasticity-linked protein induced by CRS. In conclusion, engeletin has antidepressant activity via activation of the BDNF-TrkB-mTORC1 signalling pathway and upregulation of PFC synaptic plasticity.
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Transtorno Depressivo Maior , Plasticidade Neuronal , Receptor trkB , Animais , Humanos , Camundongos , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Fator Neurotrófico Derivado do Encéfalo/efeitos dos fármacos , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Transtorno Depressivo Maior/tratamento farmacológico , Hipocampo/metabolismo , Mamíferos/metabolismo , Alvo Mecanístico do Complexo 1 de Rapamicina/efeitos dos fármacos , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Proteínas Tirosina Quinases/metabolismo , Estresse Psicológico/tratamento farmacológico , Estresse Psicológico/metabolismo , Plasticidade Neuronal/efeitos dos fármacos , Receptor trkB/efeitos dos fármacos , Receptor trkB/metabolismoRESUMO
High-mobility group box1 (HMGB1) induces inflammatory injury, and emerging reports suggest that it is critical for brain ischemia reperfusion. Engeletin, a natural Smilax glabra rhizomilax derivative, is reported to possess anti-inflammatory activity. Herein, we examined the mechanism of engeletin-mediated neuroprotection in rats having transient middle cerebral artery occlusion (tMCAO) against cerebral ischemia reperfusion injury. Male SD rats were induced using a 1.5 h tMCAO, following by reperfusion for 22.5 h. Engeletin (15, 30 or 60 mg/kg) was intravenously administered immediately following 0.5 h of ischemia. Based on our results, engeletin, in a dose-dependent fashion, reduced neurological deficits, infarct size, histopathological alterations, brain edema and inflammatory factors, namely, circulating IL-1ß, TNF-α, IL-6 and IFN-γ. Furthermore, engeletin treatment markedly reduced neuronal apoptosis, which, in turn, elevated Bcl-2 protein levels, while suppressing Bax and Cleaved Caspase-3 protein levels. Meanwhile, engeletin significantly reduces overall expressions of HMGB1, TLR4, and NF-κB and attenuated nuclear transfer of nuclear factor kappa B (NF-κB) p65 in ischemic cortical tissue. In conclusion, engeletin strongly prevents focal cerebral ischemia via suppression of the HMGB1/TLR4/NF-κB inflammatory network.
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Isquemia Encefálica , Proteína HMGB1 , Traumatismo por Reperfusão , Ratos , Masculino , Animais , NF-kappa B/genética , NF-kappa B/metabolismo , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Proteína HMGB1/genética , Proteína HMGB1/metabolismo , Transdução de Sinais , Doenças Neuroinflamatórias , Ratos Sprague-Dawley , Isquemia Encefálica/complicações , Isquemia Encefálica/tratamento farmacológico , Infarto da Artéria Cerebral Média/complicações , Infarto da Artéria Cerebral Média/tratamento farmacológico , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo , ReperfusãoRESUMO
A carbapenem-resistant Enterobacterales outbreak at a veterinary teaching hospital in the United States increased urgency for improved communication among diagnostic laboratories, public health authorities, veterinarians, and pet owners. Kansas State University, University of Missouri, Kansas Department of Health and Environment, and Veterinary Laboratory Investigation and Response Network created a surveillance, storage, and reporting protocol for veterinary antimicrobial-resistant bacteria; determined frequency of those bacteria in companion animals during 2018-2021; and created educational flyers for veterinarians and pet owners. We recommend a One Health strategy to create efficient surveillance programs to identify and report antimicrobial-resistant bacteria and educate veterinarians and pet owners about transmission risks.
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Anti-Infecciosos , Saúde Única , Animais , Saúde Pública , Carbapenêmicos/farmacologia , Hospitais Veterinários , Hospitais de Ensino , Bactérias , Antibacterianos/farmacologiaRESUMO
Mammalian orthoreovirus (MRV) infects many mammalian species including humans, bats, and domestic animals. To determine the prevalence of MRV in bats in the United States, we screened more than 900 bats of different species collected during 2015-2019 by a real-time reverse-transcription polymerase chain reaction assay; 4.4% bats tested MRV-positive and 13 MRVs were isolated. Sequence and phylogenetic analysis revealed that these isolates belonged to four different strains/genotypes of viruses in Serotypes 1 or 2, which contain genes similar to those of MRVs detected in humans, bats, bovine, and deer. Further characterization showed that these four MRV strains replicated efficiently on human, canine, monkey, ferret, and swine cell lines. The 40/Bat/USA/2018 strain belonging to the Serotype 1 demonstrated the ability to infect and transmit in pigs without prior adaptation. Taken together, this is evidence for different genotypes and serotypes of MRVs circulating in US bats, which can be a mixing vessel of MRVs that may spread to other species, including humans, resulting in cross-species infections.
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Quirópteros , Cervos , Orthoreovirus de Mamíferos , Orthoreovirus , Animais , Cães , Humanos , Bovinos , Estados Unidos , Suínos , Orthoreovirus de Mamíferos/genética , Filogenia , FurõesRESUMO
BACKGROUND: To explore the correlation of tumor necrosis factor-α-induced protein 8-like protein 3 (TIPE3) expressions in colorectal cancer (CRC) with tumor-immune infiltration and patient prognosis. METHODS: Formalin-fixed paraffin-embedded tumor samples from CRC patients (n = 110) were used in this study. Immunohistochemistry staining of TIPE3 and three prognostic immune biomarkers (CD8, CD20, and CD66b) was conducted in the tumor tissues and adjacent normal tissues. A Cox regression analysis of univariate and multivariate variables was performed to assess the correlation between TIPE3 and patient prognosis. RESULT: We found that TIPE3 was mainly expressed in the cytoplasm, with a small amount in the nucleus. The expression of TIPE3 in tumor tissues is significantly higher than in adjacent normal tissues, and it is significantly correlated with the survival rate of patients in tumor tissues (p = 0.0038) and adjacent normal tissues (p<0.0001). Patients with a high TIPE3 expression had a lower survival rate, while patients with a low TIPE3 expression had a higher survival rate. Univariate regression analysis showed that the TIPE3 expression in tumor tissues (p = 0.007), the TIPE3 expression in adjacent normal tissues (p<0.001), the number of CD8+ T cells in tumor tissues (p = 0.020), the number of CD20+ B cells in tumor tissues (p = 0.023), the number of CD20+ B cells in adjacent normal tissues (p = 0.023), the number of CD66b+ neutrophils in tumor tissues (p = 0.005), the number of CD66b+ neutrophils in adjacent normal tissues (p<0.001), lymphatic metastasis (p = 0.010), TNM stage (p = 0.013), and tumor grade (p = 0.027) were significantly correlated with overall survival (OS). These prognostic factors were then subjected to multivariate regression analysis, and the results showed that the expression of TIPE3, the number of CD8+ T cells, and the number of CD66b+ neutrophils were prognostic factors affecting the OS rate of CRC patients. CONCLUSION: We found that the TIPE3 protein is upregulated in CRC cancer tissues and is correlated with survival rate.
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Neoplasias Colorretais , Peptídeos e Proteínas de Sinalização Intracelular , Humanos , Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Metástase Linfática , Prognóstico , Fator de Necrose Tumoral alfa , Peptídeos e Proteínas de Sinalização Intracelular/genéticaRESUMO
Lactate, once recognized as a wasty product from anaerobic glycolysis, is proved to be a pivotal signal molecule. Lactate accumulation occurs in diverse physiological and pathological settings due to the imbalance between lactate production and clearance. Under the condition with drastic changes in local microenvironment, such as tumorigenesis, inflammation, and microbial infection, the glycolysis turns to be active in surrounding cells leading to increased lactate release. Meanwhile, lactate can be utilized by these cells as an energy substrate and acts as a signal molecule to regulate cell functions through receptor-dependent or independent pathways. In this review, we tended to tease out the contribution of lactate in tumor progression and immunomodulation. And we also discussed the accessory role of lactate, beyond as the energy source only, in the growth of invading pathogens.
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Glicólise , Ácido Láctico , Humanos , Ácido Láctico/metabolismo , Glicólise/fisiologia , Inflamação , Oceanos e MaresRESUMO
Many indicators, including red cell distribution width (RDW) and iron metabolism, are sensitive to a variety of risk factors, and are associated with the pathological alterations and disease onset. RDW reflects the degree of heterogeneous volumes of peripheral red blood cells (RBCs). It has been well-known that increased RDW indicates iron deficiency anemia, hemolytic anemia, ineffective erythropoiesis, and shorten lifespan of RBCs. Increased RDW is also prevalent in various non-anemic pathological conditions and diseases. We here review the factors affecting RDW, particularly disordered iron metabolism, chronic inflammation, and oxidative stress, and recapitulate the interplays among these factors. Furthermore, we review the application of increased RDW together with disordered iron homeostasis and the deregulations of hepcidin expression and ferritin levels in the diagnoses and prognosis of anemic and nonanemic diseases. RDW is inexpensive and readily available and may be valuable in adding to the diagnosis and monitoring of many pathological conditions. RDW combined with other indicators, for example, hepcidin and ferritin levels, should be utilized more frequently in clinical practice.
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Índices de Eritrócitos , Hepcidinas , Hepcidinas/metabolismo , Eritrócitos/metabolismo , Ferro/metabolismo , Ferritinas/metabolismoRESUMO
The conventional transmission and reflection operating mode switching metasurface depends on phase change materials, which are often difficult to integrate with metasurface devices and work in real time. Here, we propose an integration of a transmission-reflection metasurface that can dynamically control beam direction and functions in both transmission and reflection modes by varying the frequency of the incident wave. Remarkably, the transmission and reflection modes of terahertz beam manipulation can be obtained by illuminating only the transmission side of the metasurface. The full-wave simulation results are in good agreement with the theoretically calculated results, which verifies the terahertz wave manipulation capability of the proposed structure. This metasurface provides a design method for full-space terahertz beam regulation devices.
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Metal nanoparticles (NPs) are widely used in daily life and commercial activities owing to their unique physicochemical properties. Consequently, there is an increasing risk of daily and occupational exposure to metal NPs, which raises concerns regarding their health hazards. Programmed cell deaths (PCDs) have been clarified to be involved in metal NP-induced cytotoxicity, including apoptosis, autophagy, and pyroptosis. However, whether and how ferroptosis, a newly recognized PCD, contributes to metal NP-induced cell death remain unclear. In this study, we investigated the ferroptotic effects of two representative metal NPs, silver nanoparticles (AgNPs) and gold nanoparticles (AuNPs), on macrophages in vitro. Our results revealed that AgNPs, rather than AuNPs, induced non-apoptotic PCD, accompanied by lipid peroxidation and iron homeostasis disorders, which are two hallmarks of ferroptosis, in macrophages. Treatment with a ferroptosis inhibitor (ferrostatin-1) and iron chelator (deferoxamine) reversed AgNP-induced PCD, corroborating the induction of ferroptosis upon exposure to AgNPs. Moreover, our results revealed that smaller AgNPs elicited greater ferroptotic effects on macrophages than larger ones. Importantly, ferroptosis in AgNP-treated macrophages was mainly triggered by AgNPs per se rather than by Ag ions. Overall, our study highlights the ferroptotic effects elicited by AgNPs in macrophages, which will promote the understanding of their cytotoxic effects and facilitate the safer design of metal nanoproducts.
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Ferroptose , Nanopartículas Metálicas , Prata/química , Ouro/química , Nanopartículas Metálicas/toxicidade , Nanopartículas Metálicas/química , ApoptoseRESUMO
The retinoid-related orphan receptor α (RORα) is one subfamily of nuclear hormone receptors (NRs). This review summarizes the understanding and potential effects of RORα in the cardiovascular system and then analyzes current advances, limitations and challenges, and further strategy for RORα-related drugs in cardiovascular diseases. Besides regulating circadian rhythm, RORα also influences a wide range of physiological and pathological processes in the cardiovascular system, including atherosclerosis, hypoxia or ischemia, myocardial ischemia/reperfusion injury, diabetic cardiomyopathy, hypertension, and myocardial hypertrophy. In terms of mechanism, RORα was involved in the regulation of inflammation, apoptosis, autophagy, oxidative stress, endoplasmic reticulum (ER) stress, and mitochondrial function. Besides natural ligands for RORα, several synthetic RORα agonists or antagonists have been developed. This review mainly summarizes protective roles and possible mechanisms of RORα against cardiovascular diseases. However, there are also several limitations and challenges of current research on RORα, especially the difficulties on the transformability from the bench to the bedside. By the aid of multidisciplinary research, breakthrough progress on RORα-related drugs to combat cardiovascular disorder may appear.
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Doenças Cardiovasculares , Cardiomiopatias Diabéticas , Humanos , Cardiomegalia , Membro 1 do Grupo F da Subfamília 1 de Receptores Nucleares , Receptores Citoplasmáticos e Nucleares , RetinoidesRESUMO
OBJECTIVES: To translate, cross-culturally adapt, and validate the Geriatric 8 (G8) questionnaire in Chinese hospitalized older adults with cancer. METHODS: The Chinese version of the G8 (C-G8) was produced following Brislin's guidelines. The psychometric properties of the C-G8 were evaluated among 296 eligible patients. RESULTS: The content validity index of the C-G8 was 0.8â¼1 at the item level and 0.975 at the scale level. The C-G8 identified more frail individuals among these older (>75 years) participants compared to their younger (65â¼75 years) counterparts (frailty prevalence: 87.1% vs. 70.9%, P=0.010). The convergent validity of the C-G8 was tested by correlating it with the FRAIL scale (r=-0.592, P<0.001). The C-G8 had a lower internal consistency (Cronbach's α coefficient=0.501) but higher test-retest reliability and inter-rater reliability (intraclass correlation coefficient=0.913 and 0.993, respectively, P<0.001). CONCLUSIONS: The C-G8 questionnaire presented acceptable validity and reliability and could be used in Chinese hospitalized older adults with cancer.