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The TRPV3 channel plays vital roles in skin physiology. Dysfunction of TRPV3 causes skin diseases, including Olmsted syndrome. However, the lack of potent and selective inhibitors impedes the validation of TRPV3 as a therapeutic target. In this study, we identified Trpvicin as a potent and subtype-selective inhibitor of TRPV3. Trpvicin exhibits pharmacological potential in the inhibition of itch and hair loss in mouse models. Cryogenic electron microscopy structures of TRPV3 and the pathogenic G573S mutant complexed with Trpvicin reveal detailed ligand-binding sites, suggesting that Trpvicin inhibits the TRPV3 channel by stabilizing it in a closed state. Our G573S mutant structures demonstrate that the mutation causes a dilated pore, generating constitutive opening activity. Trpvicin accesses additional binding sites inside the central cavity of the G573S mutant to remodel the channel symmetry and block the channel. Together, our results provide mechanistic insights into the inhibition of TRPV3 by Trpvicin and support TRPV3-related drug development.
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Canais de Cátion TRPV , Camundongos , Animais , Canais de Cátion TRPV/genética , Canais de Cátion TRPV/química , Mutação , Sítios de LigaçãoRESUMO
Changes in intracellular nicotinamide adenine dinucleotide (NAD+) levels have been observed in various disease states. A decrease in NAD+ levels has been noted following spinal cord injury (SCI). Nicotinamide riboside (NR) serves as the precursor of NAD+. Previous research has demonstrated the anti-inflammatory and apoptosis-reducing effects of NR supplements. However, it remains unclear whether NR exerts a similar role in mice after SCI. The objective of this study was to investigate the impact of NR on these changes in a mouse model of SCI. Four groups were considered: (1) non-SCI without NR (Sham), (2) non-SCI with NR (Sham +NR), (3) SCI without NR (SCI), and (4) SCI with NR (SCI + NR). Female C57BL/6J mice aged 6-8 weeks were intraperitoneally administered with 500 mg/kg/day NR for a duration of one week. The supplementation of NR resulted in a significant elevation of NAD+ levels in the spinal cord tissue of mice after SCI. In comparison to the SCI group, NR supplementation exhibited regulatory effects on the chemotaxis/recruitment of leukocytes, leading to reduced levels of inflammatory factors such as IL-1ß, TNF-α, and IL-22 in the injured area. Moreover, NR supplementation notably enhanced the survival of neurons and synapses within the injured area, ultimately resulting in improved motor functions after SCI. Therefore, our research findings demonstrated that NR supplementation had inhibitory effects on leukocyte chemotaxis, anti-inflammatory effects, and could significantly improve the immune micro-environment after SCI, thereby promoting neuronal survival and ultimately enhancing the recovery of motor functions after SCI. NR supplementation showed promise as a potential clinical treatment strategy for SCI.
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6-methoxybenzoxazolinone (6-MBOA) is a secondary plant metabolite predominantly found in monocotyledonous plants, especially Gramineae. In damaged tissue, 2-ß-D-glucopyranosyloxy-4-hydroxy-7-methoxy-1,4-benzoxazin-3-one (DIMBOA-Glc) is hydrolyzed to DIMBOA, which spontaneously decomposes into 6-MBOA. It is commonly detected in plants consumed by voles and livestock and can also be present in cereal-based products. Discovered in 1955, this compound is renowned for its ability to trigger animal reproduction. However, there is a lack of research on its functional and mechanistic properties, leaving much of their potential unexplored. This review aimed to comprehensively summarize the effects of 6-MBOA on animal reproduction and human health, as well as its defensive role against herbivores. Studies have shown that 6-MBOA effectively inhibits the digestion, development, growth, and reproduction of insects. 6-MBOA may act as a partial agonist of melatonin and exert a regulatory role in mammalian reproduction, resulting in either promoting or inhibiting effects. 6-MBOA has been theorized to possess anti-tumor, anti-AIDS, anti-anxiety, and weight-loss effects in humans. However, insufficient attention has been paid to its defense properties against mammalian herbivores, and the mechanisms underlying its effects on mammalian reproduction remain unclear. In addition, research on its impact on human health is still in its preliminary stages. The review emphasizes the need for further systematic and comprehensive research on 6-MBOA to fully understand its diverse functions. Elucidating the effects of 6-MBOA on animal reproduction, adaptation, and human health would advance our understanding of plant-herbivore coevolution and the influence of environmental factors on animal population dynamics. Furthermore, this knowledge could potentially promote its application in human health and animal husbandry.
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Reprodução , Animais , Reprodução/efeitos dos fármacos , Reprodução/fisiologia , Humanos , BenzoxazóisRESUMO
BACKGROUND: As a common disabling disease, irreversible neuronal death due to spinal cord injury (SCI) is the root cause of functional impairment; however, the capacity for neuronal regeneration in the developing spinal cord tissue is limited. Therefore, there is an urgent need to investigate how defective neurons can be replenished and functionally integrated by neural regeneration; the reprogramming of intrinsic cells into functional neurons may represent an ideal solution. METHODS: A mouse model of transection SCI was prepared by forceps clamping, and an adeno-associated virus (AAV) carrying the transcription factors NeuroD1 and Neurogenin-2(Ngn2) was injected in situ into the spinal cord to specifically overexpress these transcription factors in astrocytes close to the injury site. 5-bromo-2´-deoxyuridine (BrdU) was subsequently injected intraperitoneally to continuously track cell regeneration, neuroblasts and immature neurons marker expression, neuronal regeneration, and glial scar regeneration. In addition, immunoprotein blotting was used to measure the levels of transforming growth factor-ß (TGF-ß) pathway-related protein expression. We also evaluated motor function, sensory function, and the integrity of the blood-spinal cord barrier(BSCB). RESULTS: The in situ overexpression of NeuroD1 and Ngn2 in the spinal cord was achieved by specific AAV vectors. This intervention led to a significant increase in cell regeneration and the proportion of cells with neuroblasts and immature neurons cell properties at the injury site(p < 0.0001). Immunofluorescence staining identified astrocytes with neuroblasts and immature neurons cell properties at the site of injury while neuronal marker-specific staining revealed an increased number of mature astrocytes at the injury site. Behavioral assessments showed that the intervention did not improve The BMS (Basso mouse scale) score (p = 0.0726) and gait (p > 0.05), although the treated mice had more sensory sensitivity and greater voluntary motor ability in open field than the non-intervention mice. We observed significant repair of the BSCB at the center of the injury site (p < 0.0001) and a significant improvement in glial scar proliferation. Electrophysiological assessments revealed a significant improvement in spinal nerve conduction (p < 0.0001) while immunostaining revealed that the levels of TGF-ß protein at the site of injury in the intervention group were lower than control group (p = 0.0034); in addition, P70 s6 and PP2A related to the TGF-ß pathway showed ascending trend (p = 0.0036, p = 0.0152 respectively). CONCLUSIONS: The in situ overexpression of NeuroD1 and Ngn2 in the spinal cord after spinal cord injury can reprogram astrocytes into neurons and significantly enhance cell regeneration at the injury site. The reprogramming of astrocytes can lead to tissue repair, thus improving the reduced threshold and increasing voluntary movements. This strategy can also improve the integrity of the blood-spinal cord barrier and enhance nerve conduction function. However, the simple reprogramming of astrocytes cannot lead to significant improvements in the striding function of the lower limbs.
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Astrócitos , Fatores de Transcrição Hélice-Alça-Hélice Básicos , Modelos Animais de Doenças , Proteínas do Tecido Nervoso , Traumatismos da Medula Espinal , Animais , Traumatismos da Medula Espinal/terapia , Traumatismos da Medula Espinal/fisiopatologia , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Astrócitos/fisiologia , Proteínas do Tecido Nervoso/metabolismo , Camundongos , Regeneração Nervosa/fisiologia , Neurônios , Feminino , Camundongos Endogâmicos C57BL , Medula Espinal/metabolismoRESUMO
Bacterial adaptation is largely shaped by horizontal gene transfer, xenogeneic silencing mediated by lineage-specific DNA bridgers (H-NS, Lsr2, MvaT and Rok), and various anti-silencing mechanisms. No xenogeneic silencing DNA bridger is known for α-proteobacteria, from which mitochondria evolved. By investigating α-proteobacterium Sinorhizobium fredii, a facultative legume microsymbiont, here we report the conserved zinc-finger bearing MucR as a novel xenogeneic silencing DNA bridger. Self-association mediated by its N-terminal domain (NTD) is required for DNA-MucR-DNA bridging complex formation, maximizing MucR stability, transcriptional silencing, and efficient symbiosis in legume nodules. Essential roles of NTD, CTD (C-terminal DNA-binding domain), or full-length MucR in symbiosis can be replaced by non-homologous NTD, CTD, or full-length protein of H-NS from γ-proteobacterium Escherichia coli, while NTD rather than CTD of Lsr2 from Gram-positive Mycobacterium tuberculosis can replace the corresponding domain of MucR in symbiosis. Chromatin immunoprecipitation sequencing reveals similar recruitment profiles of H-NS, MucR and various functional chimeric xenogeneic silencers across the multipartite genome of S. fredii, i.e. preferring AT-rich genomic islands and symbiosis plasmid with key symbiosis genes as shared targets. Collectively, the convergently evolved DNA bridger MucR predisposed α-proteobacteria to integrate AT-rich foreign DNA including symbiosis genes, horizontal transfer of which is strongly selected in nature.
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Alphaproteobacteria , Regulação Bacteriana da Expressão Gênica , Alphaproteobacteria/genética , Proteínas de Bactérias/metabolismo , DNA , Escherichia coli/genética , Escherichia coli/metabolismo , SimbioseRESUMO
Oligodendrocyte progenitor cells (OPCs) originate in the ventricular zone (VZ) of the brain and spinal cord, and their primary function is to differentiate into oligodendrocytes (OLs). Studies have shown that OPCs and OLs are pathologically and physiologically heterogeneous. Previous transcriptome analyses used Bulk RNA-seq, which compares average gene expression in cells and does not allow for heterogeneity. In recent years, the development of single-cell sequencing (scRNA-seq) and single-cell nuclear sequencing (snRNA-seq) has allowed us to study an individual cell. In this review, sc/snRNA-seq was used to study the different subpopulations of OL lineage cells, their developmental trajectories, and their applications in related diseases. These techniques can distinguish different subpopulations of cells, and identify differentially expressed genes in particular cell types under certain conditions, such as treatment or disease. It is of great significance to the study of the occurrence, prevention, and treatment of various diseases.
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Oligodendroglia , Medula Espinal , Linhagem da Célula , Oligodendroglia/metabolismo , Encéfalo , RNA Nuclear Pequeno/metabolismo , Diferenciação Celular/fisiologiaRESUMO
Bacterial strain Y-6T, isolated from a landfill site in Yiwu, PR China, was characterized using a polyphasic taxonomy approach. Cells were Gram-stain-negative, aerobic, rod-shaped, motile by means of a single polar flagellum and formed pale beige colonies. Strain Y-6T grew at 4-40 °C (optimal at 30-37 °C), pH 6.5-9.5 (optimal at pH 7.2-8.5) and in the presence of 0.5-10.0â% (w/v) NaCl (optimal at 1.0-3.0â%). Phylogenetic analysis revealed that strain Y-6T was a member of the genus Aliidiomarina and closely related to Aliidiomarina taiwanensis MCCC 1A06493T with a 16S rRNA sequence similarity of 98.2â%. The major cellular fatty acids of the isolate were iso-C15â:â0, C16â:â0, iso-C17â:â0 and summed feature 9 (iso-C17â:â1 ω9c and/or 10-methyl-C16â:â0). Q-8 was the predominant ubiquinone. The major polar lipids comprised diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, aminoglycophospholipid, aminophospholipid, phospholipid, three glycolipids and two unknown lipids. The genomic DNA G+C content was 46.6âmol%. The digital DNA-DNA hybridization value between Y-6T and A. taiwanensis MCCC 1A06493T was 18.3â%. Strain Y-6T had an average nucleotide identity value of 74.09â% with A. taiwanensis MCCC 1A06493T. Results from the polyphasic taxonomy study support the conclusion that strain Y-6T represents a novel Aliidiomarina species, for which the name Aliidiomarina quisquiliarum sp.nov. is proposed. The type strain is Y-6T (=MCCC 1K06228T=KCTC 82676T).
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Ácidos Graxos , Poluentes Químicos da Água , Ácidos Graxos/química , Filogenia , RNA Ribossômico 16S/genética , DNA Bacteriano/genética , Composição de Bases , Análise de Sequência de DNA , Técnicas de Tipagem Bacteriana , Fosfolipídeos/química , ChinaRESUMO
Body movements provide a rich source of emotional information during social interactions. Although the ability to perceive biological motion cues related to those movements begins to develop during infancy, processing those cues to identify emotions likely continues to develop into childhood. Previous studies used posed or exaggerated body movements, which might not reflect the kind of body expressions children experience. The current study used an event-related potential (ERP) priming paradigm to investigate the development of emotion recognition from more naturalistic body movements. Point-light displays (PLDs) of male adult bodies expressing happy or angry emotional movements while narrating a story were used as prime stimuli, whereas audio recordings of the words "happy" and "angry" spoken with an emotionally neutral prosody were used as targets. We recorded the ERPs time-locked to the onset of the auditory target from 3- and 6-year-old children, and we compared amplitude and latency of the N300 and N400 responses between the two age groups in the different prime-target conditions. There was an overall effect of prime for the N300 amplitude, with more negative-going responses for happy PLDs compared with angry PLDs. There was also an interaction between prime and target for the N300 latency, suggesting that all children were sensitive to the emotional congruency between body movements and words. For the N400 component, there was only an interaction among age, prime, and target for latency, suggesting an age-dependent modulation of this component when prime and target did not match in emotional information. Overall, our results suggest that the emergence of more complex emotion processing of body expressions occurs around 6 years of age, but it is not fully developed at this point in ontogeny.
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Eletroencefalografia , Potenciais Evocados , Adulto , Ira , Criança , Pré-Escolar , Sinais (Psicologia) , Emoções/fisiologia , Potenciais Evocados/fisiologia , Expressão Facial , Feminino , Humanos , MasculinoRESUMO
This study aims to identify the chemical constituents of Simiao Yong'an Decoction based on ultra-performance liquid chromatography coupled with linear quadrupole ion trap-orbitrap mass spectrometry(UPLC-LTQ-Orbitrap-MS). The elution was performed through a UPLC BEH C_(18) column(2.1 mm × 100 mm, 1.7 µm) with the mobile phase of water(containing 0.1% formic acid)-acetonitrile at a flow rate of 0.4 mL·min~(-1). LTQ-Orbitrap-MS with heat electrospray ion(HESI) source was employed to collect MS fragment information in the negative ion mode. A total of 72 compounds were identified based on reference substance comparison, fragmentation rules, accurate molecular weight, related reports and databases(MassBank and HMDB), including 30 iridoid glycosides, 9 organic acids, 15 flavonoids, 10 phenylpropanoids, 7 triterpenoids, and 1 saccharide. The method established in this study is comprehensive, rapid, and accurate, which can help summarize the fragmentation rules of constituents and provide reference for revealing the active constituents and pharmacodynamic mechanism of Simiao Yong'an Decoction.
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Medicamentos de Ervas Chinesas , Triterpenos , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia Líquida , Medicamentos de Ervas Chinesas/química , Flavonoides/análise , Triterpenos/análiseRESUMO
As the number of EEG papers increases, so too do the number of guidelines for how to report what has been done. However, current guidelines and checklists appear to have limited adoption, as systematic reviews have shown the journal article format is highly prone to errors, ambiguities and omissions of methodological details. This is a problem for transparency in the scientific record, along with reproducibility and metascience. Following lessons learned in the high complexity fields of aviation and surgery, we conclude that new tools are needed to overcome the limitations of written methodology descriptions, and that these tools should be developed through community consultation to ensure that they have the most utility for EEG stakeholders. As a first step in tool development, we present the ARTEM-IS Statement describing what action will be needed to create an Agreed Reporting Template for Electroencephalography Methodology - International Standard (ARTEM-IS), along with ARTEM-IS Design Guidelines for developing tools that use an evidence-based approach to error reduction. We first launched the statement at the LiveMEEG conference in 2020 along with a draft of an ARTEM-IS template for public consultation. Members of the EEG community are invited to join this collective effort to create evidence-based tools that will help make the process of reporting methodology intuitive to complete and foolproof by design.
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Eletroencefalografia , Guias como Assunto , Relatório de Pesquisa/normas , Humanos , Publicações Periódicas como Assunto , Reprodutibilidade dos TestesRESUMO
The 2019 novel coronavirus has spread rapidly around the world. Cancer patients seem to be more susceptible to infection and disease deterioration, but the factors affecting the deterioration remain unclear. We aimed to develop an individualized model for prediction of coronavirus disease (COVID-19) deterioration in cancer patients. The clinical data of 276 cancer patients diagnosed with COVID-19 in 33 designated hospitals of Hubei, China from December 21, 2019 to March 18, 2020, were collected and randomly divided into a training and a validation cohort by a ratio of 2:1. Cox stepwise regression analysis was carried out to select prognostic factors. The prediction model was developed in the training cohort. The predictive accuracy of the model was quantified by C-index and time-dependent area under the receiver operating characteristic curve (t-AUC). Internal validation was assessed by the validation cohort. Risk stratification based on the model was carried out. Decision curve analysis (DCA) were used to evaluate the clinical usefulness of the model. We found age, cancer type, computed tomography baseline image features (ground glass opacity and consolidation), laboratory findings (lymphocyte count, serum levels of C-reactive protein, aspartate aminotransferase, direct bilirubin, urea, and d-dimer) were significantly associated with symptomatic deterioration. The C-index of the model was 0.755 in the training cohort and 0.779 in the validation cohort. The t-AUC values were above 0.7 within 8 weeks both in the training and validation cohorts. Patients were divided into two risk groups based on the nomogram: low-risk (total points ≤ 9.98) and high-risk (total points > 9.98) group. The Kaplan-Meier deterioration-free survival of COVID-19 curves presented significant discrimination between the two risk groups in both training and validation cohorts. The model indicated good clinical applicability by DCA curves. This study presents an individualized nomogram model to individually predict the possibility of symptomatic deterioration of COVID-19 in patients with cancer.
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COVID-19/mortalidade , Neoplasias/virologia , Nomogramas , Idoso , Área Sob a Curva , China , Técnicas de Apoio para a Decisão , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/mortalidade , Medicina de Precisão , Estudos Retrospectivos , Fatores de Risco , Análise de SobrevidaRESUMO
ABSTRACT: This study summarized the literature regarding the application of pre-bent titanium miniplates in orthognathic surgery and evaluated the extra deformation of the manually pre-bent titanium miniplates via finite element analysis for acquiring higher surgical accuracy. The literature was reviewed with a chart. Three models of titanium miniplates with different thicknesses (1.0âmm, 0.8âmm, 0.6âmm) were created using COMSOL Multiphysics software for biomechanical behavior analysis. The 3 models were virtually bent into 5 angles (15 degree, 30 degree, 45 degree, 60 degree, 80 degree). respectively to simulate the preoperative virtual bending, then to simulate the practical manual bending via finite element analysis. The stresses and displacements of these models were recorded. The models from virtual bending simulation and manual bending simulation were registered to analyze the deviations. The results showed that the maximum stress and the displacement deviations between the virtual bending models and the manual bending models increased with the thickness and bending angle of the pre-bent miniplate models. To improve the surgical accuracy, measures should be applied to the manually pre-bent titanium miniplates to reduce the extra deformation when the plate being thicker and the bending angle being larger.
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Cirurgia Ortognática , Procedimentos Cirúrgicos Ortognáticos , Placas Ósseas , Análise de Elementos Finitos , Fixação Interna de Fraturas , Humanos , Estresse Mecânico , TitânioRESUMO
OBJECTIVE: To establish a method for extracting Listeria monocytogenesmembrane vesicles (LM-MVs) and to analyze the characteristics of LM-MVs and their ability to induce innate immune effect in vitro so as to lay the foundation for research into using LM-MVs as vaccine carrier and drug delivery platform. METHODS: The membrane vesicles secreted by Listeria monocytogenes were extracted through a continuous process, including culturing, centrifugation, filtration, ultrafiltration concentration and ultracentrifugation. The morphological characteristics of LM-MVs were observed with transmission electron microscope, and particle size distribution were measured by dynamic light scattering analysis. SDS-PAGE and Western blot were used to analyze the protein composition of LM-MVs. CCK-8 cell proliferation and toxicity determination experiments were done to analyze their effect on the proliferation of innate immune cells, and qPCR was used to analyze their ability to induce innate immune responses. RESULTS: A method for extracting LM-MVs was successfully established. Under the transmission electron microscope, LM-MVs presented a nearly circular film-like structure, and dynamic light scattering analysis showed that their sizes were between 65 and 190 nm. SDS-PAGE and Western blot showed that LM-MVs contained proteins, including listeriolysin O (LLO). CCK-8 cell proliferation and toxicity experiment showed that after intervention with 10, 20 and 50 µg/mL of LM-MVs for 24 hours, the proliferation rate of DC 2.4 mouse dendritic cell line was higher than that of non-interventional DC 2.4 cells ( P<0.05); after intervention with 0.1, 1, 10, 20 and 50 µg/mL of LM-MVs for 24 hours, the proliferation rate of RAW 264.7 cells was higher than that of non-interventional RAW 264.7 cells ( P<0.01). The results of qPCR showed that, after intervention with 50 µg/mL of LM-MVs, the expression levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6 and IL-10 in RAW 264.7 cells were higher than those of non-intervention control cells ( P<0.05). CONCLUSIONS: The method established in the study can be used to extract LM-MVs. The extracted LM-MVs have a diameter of 65-190 nm and a nearly circular membrane-like structure. They can secrete a variety of protein components and stimulate innate immune responses.
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Listeria monocytogenes , Animais , Linhagem Celular , Células Dendríticas , Camundongos , Células RAW 264.7RESUMO
BACKGROUND: Changeful seasonal influenza activity in subtropical areas such as Taiwan causes problems in epidemic preparedness. The Taiwan Centers for Disease Control has maintained real-time national influenza surveillance systems since 2004. Except for timely monitoring, epidemic forecasting using the national influenza surveillance data can provide pivotal information for public health response. OBJECTIVE: We aimed to develop predictive models using machine learning to provide real-time influenza-like illness forecasts. METHODS: Using surveillance data of influenza-like illness visits from emergency departments (from the Real-Time Outbreak and Disease Surveillance System), outpatient departments (from the National Health Insurance database), and the records of patients with severe influenza with complications (from the National Notifiable Disease Surveillance System), we developed 4 machine learning models (autoregressive integrated moving average, random forest, support vector regression, and extreme gradient boosting) to produce weekly influenza-like illness predictions for a given week and 3 subsequent weeks. We established a framework of the machine learning models and used an ensemble approach called stacking to integrate these predictions. We trained the models using historical data from 2008-2014. We evaluated their predictive ability during 2015-2017 for each of the 4-week time periods using Pearson correlation, mean absolute percentage error (MAPE), and hit rate of trend prediction. A dashboard website was built to visualize the forecasts, and the results of real-world implementation of this forecasting framework in 2018 were evaluated using the same metrics. RESULTS: All models could accurately predict the timing and magnitudes of the seasonal peaks in the then-current week (nowcast) (ρ=0.802-0.965; MAPE: 5.2%-9.2%; hit rate: 0.577-0.756), 1-week (ρ=0.803-0.918; MAPE: 8.3%-11.8%; hit rate: 0.643-0.747), 2-week (ρ=0.783-0.867; MAPE: 10.1%-15.3%; hit rate: 0.669-0.734), and 3-week forecasts (ρ=0.676-0.801; MAPE: 12.0%-18.9%; hit rate: 0.643-0.786), especially the ensemble model. In real-world implementation in 2018, the forecasting performance was still accurate in nowcasts (ρ=0.875-0.969; MAPE: 5.3%-8.0%; hit rate: 0.582-0.782) and remained satisfactory in 3-week forecasts (ρ=0.721-0.908; MAPE: 7.6%-13.5%; hit rate: 0.596-0.904). CONCLUSIONS: This machine learning and ensemble approach can make accurate, real-time influenza-like illness forecasts for a 4-week period, and thus, facilitate decision making.
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Surtos de Doenças/estatística & dados numéricos , Influenza Humana/epidemiologia , Aprendizado de Máquina/normas , Previsões , Humanos , TaiwanRESUMO
The aim of this study is to evaluate the osteogenesis around titanium implant and in bone defect or fracture in jaw bones and long bones in ovariectomized (OVX) animal models. The literature on the osteogenesis around titanium implant and in bone defect or fracture in jaw bones and long bones was reviewed with charts. Fourty-eight rats were randomly divided into OVX group with ovariectomy and SHAM (sham-surgery) group with sham surgery. Titanium implants were inserted in the right mandibles and tibiae; bone defects were created in the left mandibles and tibiae. Two-week postoperatively, mandibles and tibiae of 8 rats were harvested and examined by hematoxylin and eosin staining and histological analysis; 4-week postoperatively, all mandibles and tibiae were harvested and examined by Micro-CT and histological analysis. A total of 52 articles were included in this literature review. Tibial osteogenesis around titanium implant and in bone defect in OVX group were significantly decreased compared with SHAM group. However, osteogenesis differences in the mandible both around titanium implant and in bone defect between groups were not statistically significant. OVX-induced osteoporosis suppresses osteogenesis around titanium implant and in the bone defect or fracture in long bones significantly while has less effect on that in the jaw bones.
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Implantes Experimentais/efeitos adversos , Arcada Osseodentária/efeitos dos fármacos , Tíbia/efeitos dos fármacos , Titânio/farmacologia , Animais , Feminino , Procedimentos Cirúrgicos Ortognáticos , Osteogênese/efeitos dos fármacos , Osteoporose/induzido quimicamente , Osteoporose/patologia , Ovariectomia , Ratos , Tíbia/cirurgiaRESUMO
Fu-Ke-Zai-Zao pills, the famous traditional Chinese medicine formula, composed of 42 medicinal herbs, have been widely used to treat various gynecological diseases. However, the chemical constituents and metabolic profiling of Fu-Ke-Zai-Zao pills remain largely unknown, which hampers improvement of the quality control and pharmacological elucidation of this formula. In the present study, a sensitive and selective ultra high performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry method was developed to separate and identify the comprehensive chemical constituents of Fu-Ke-Zai-Zao pills. According to the results, a total of 83 compounds were identified, including phenylpropionic acids, flavonoids, terpenoids, triterpene saponins, and phthalides, and 81 compounds were first reported in Fu-Ke-Zai-Zao pills. Moreover, the absorbed components and metabolites in rat plasma after intragastric administration of Fu-Ke-Zai-Zao pills were also detected by the same analytical method. A total of 36 compounds were identified, including 21 prototypes and 15 metabolites. The latter were generated through the metabolic pathways of methylation and glucuronidation, and glucuronidated metabolites were the main constituents in the plasma. This is the first systematic study on the chemical constituents and metabolic profiling of Fu-Ke-Zai-Zao pills, and the results provide valuable chemical information for further elucidating pharmacological effects and mechanism of action of Fu-Ke-Zai-Zao pills.
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Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacocinética , Animais , Benzofuranos/análise , Cromatografia Líquida de Alta Pressão , Feminino , Flavonoides/análise , Metilação , Monoterpenos/análise , Plasma/química , Propionatos/análise , Controle de Qualidade , Ratos , Ratos Sprague-Dawley , Saponinas/análise , Espectrometria de Massas em Tandem , Triterpenos/análiseRESUMO
Traditional Chinese medicine( TCM) decoction contains complex bitterness. In this paper,the simple mixing of TCM monomer bitter substances is used as the entry point to study the law of bitterness superposition. With berberine hydrochloride( alkaloids),geniposide( terpenoids),and arbutin( glycosides) as mother liquor,sophoridine( alkaloids),gentiopicroside( terpenoids),and puerarin( glycosides) as additive substances,these different additive substances were mixed with different mother liquor according to concentration gradients to form different liquid mixtures. The bitterness of the additive solution and the mixtures was evaluated by traditional human taste panel method( THTPM) and electronic tongue; the bitterness-concentration fitting model of the additive solution and the liquid mixtures was established by Weibull and logarithmic curves. By comparing and analyzing the bitterness-concentration model and the bitterness difference( ΔI_0/ΔI_e) of the additive solution and the mixture,the influence of mother liquor on the bitterness of the mixture was investigated. The results showed that both the additive solution bitterness model and the liquid mixture bitterness model were consistent with the Weibull model and the logarithmic model( THTPM: R~2≥0. 887 0,P<0. 01; electronic tongue test:R~2≥0. 753 2,P<0. 05). The fitting degree of the Weibull model was generally higher than that of the logarithmic model; the bitterness difference( ΔI_0) was monotonously decreasing; the fitting equation of tongue bitterness and electronic tongue bitterness: R~2≥0. 874 2,P<0. 01. In this article,through the superposition of different kinds of TCM bitter substances,THTPM and electronic tongue test was combined. It was found that the bitterness after superposition was still in Weibull or logarithmic relationship with the concentration of additive substances; THTPM showed that the effect of bitter mother liquor on the bitterness of the mixture decreased with the increase of the concentration of the additive; the bitterness of the electronic tongue was obviously related to the bitterness of THTPM. However,further verification is needed later by optimizing the concentration gradient and expanding the sample size.
Assuntos
Nariz Eletrônico , Medicina Tradicional Chinesa , Paladar , Alcaloides/análise , Glicosídeos/análise , Humanos , Terpenos/análiseRESUMO
BACKGROUND: The prognostic value of central lymph node (CLN) status in papillary thyroid cancer (PTC) remains controversial. This study aimed to provide the first evidence on this issue for the aggressive tall-cell variant (TCV) subtype. METHODS: The study identified TCV patients from the Surveillance, Epidemiology, and End Results database. The Kaplan-Meier method, log-rank test, and multivariate Cox regression models were used for analysis. RESULTS: Of the 744 patients included, 404 were recorded as N0, which were pathologically or only clinically confirmed. Overall survival (OS) and cancer-specific survival (CSS) did not differ significantly between the N0 and pN1a patients (p > 0.05). To investigate the reason, the N0 patients were subdivided according to the number of examined lymph nodes (ELN). The patients with a N0 diagnosis confirmed by two or more ELNs (N0-e2+) showed significantly better outcomes than the pN1a patients and their N0 counterparts without ELN (N0-e0) (p < 0.05), whereas the N0-e0 and pN1a groups demonstrated comparable outcomes in both the log-rank and multivariate analyses (p > 0.05). Moreover, the subgroup analyses showed that even among the patients with early T-staging (T1-T2) or receipt of radioactive iodine (RAI) therapy, the N0-e0 patients still demonstrated compromised OS compared with the N0-e2+ group (p < 0.05). CONCLUSION: The cN0 patients without ELN (N0-e0) had outcomes similar to those of the pN1a patients, but showed a poorer OS than the N0-e2+ group regardless of T-staging and RAI administration, suggesting that occult CLN metastases might act as a negative prognosticator in cN0 TCV. Therefore, prophylactic central neck dissection might be considered for biopsy-proven cN0 TCV patients. Prospective studies are expected to further validate our conclusions.
Assuntos
Carcinoma Papilar/secundário , Radioisótopos do Iodo/uso terapêutico , Linfonodos/patologia , Radioterapia Adjuvante/mortalidade , Neoplasias da Glândula Tireoide/patologia , Tireoidectomia/mortalidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Papilar/radioterapia , Carcinoma Papilar/cirurgia , Terapia Combinada , Feminino , Seguimentos , Humanos , Linfonodos/efeitos da radiação , Linfonodos/cirurgia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Neoplasias da Glândula Tireoide/radioterapia , Neoplasias da Glândula Tireoide/cirurgia , Adulto JovemRESUMO
Zearalenone (ZEA) is a mycotoxin produced by fusarium graminearum. It can cause abnormal reproductive function by acting as an environmental estrogen. Research has traditionally focused on acute and chronic injury on mammalian reproductive capacity after ZEA treatment. Little research has been done studying the effects of ZEA exposure on early oogenesis. In this study, we investigate the effects of ZEA exposure on meiotic entry, DNA double-strand breaks (DSBs), and primordial follicle assembly during murine early oogenesis. The results show that ZEA exposure significantly decreased the percentage of diplotene stage germ cells, and made more germ cells remain at zygotene or pachytene stages. Moreover, the mRNA expression level of meiosis-related genes was significantly reduced after ZEA treatment. ZEA exposure significantly increased DNA-DSBs at the diplotene stage. Meanwhile, DNA damage repair genes such as RAD51 and BRCA1 were activated. Furthermore, maternal exposure to ZEA significantly decreased the number of primordial follicles in newborn mouse ovaries. In conclusion, ZEA exposure impairs mouse female germ cell meiotic progression, DNA-DSBs, and primordial follicle assembly.
Assuntos
Disruptores Endócrinos/toxicidade , Estrogênios não Esteroides/toxicidade , Meiose/efeitos dos fármacos , Oogênese/efeitos dos fármacos , Folículo Ovariano/efeitos dos fármacos , Óvulo/efeitos dos fármacos , Zearalenona/toxicidade , Animais , Proteína BRCA1 , Quebras de DNA de Cadeia Dupla , Reparo do DNA/efeitos dos fármacos , Feminino , Prófase Meiótica I/efeitos dos fármacos , Camundongos , Folículo Ovariano/metabolismo , Folículo Ovariano/patologia , Óvulo/metabolismo , Óvulo/patologia , Gravidez , Rad51 Recombinase/metabolismo , Medição de Risco , Proteínas Supressoras de Tumor/metabolismoRESUMO
This paper investigates how to efficiently charge sensor nodes in a wireless rechargeable sensor network (WRSN) with radio frequency (RF) chargers to make the network sustainable. An RF charger is assumed to be equipped with a uniform circular array (UCA) of 12 antennas with the radius λ, where λ is the RF wavelength. The UCA can steer most RF energy in a target direction to charge a specific WRSN node by the beamforming technology. Two evolutionary algorithms (EAs) using the evolution strategy (ES), namely the Evolutionary Beamforming Optimization (EBO) algorithm and the Evolutionary Beamforming Optimization Reseeding (EBO-R) algorithm, are proposed to nearly optimize the power ratio of the UCA beamforming peak side lobe (PSL) and the main lobe (ML) aimed at the given target direction. The proposed algorithms are simulated for performance evaluation and are compared with a related algorithm, called Particle Swarm Optimization Gravitational Search Algorithm-Explore (PSOGSA-Explore), to show their superiority.