RESUMO
Diffusion tensor imaging (DTI) is a prevalent magnetic resonance imaging (MRI) technique, widely used in clinical and neuroscience research. However, the reliability of DTI is affected by the low signal-to-noise ratio inherent in diffusion-weighted (DW) images. Deep learning (DL) has shown promise in improving the quality of DTI, but its limited generalization to variable acquisition schemes hinders practical applications. This study aims to develop a generalized, accurate, and efficient DL-based DTI method. By leveraging the representation of voxel-wise diffusion MRI (dMRI) signals on the sphere using spherical harmonics (SH), we propose a novel approach that utilizes SH coefficient maps as input to a network for predicting the diffusion tensor (DT) field, enabling improved generalization. Extensive experiments were conducted on simulated and in-vivo datasets, covering various DTI application scenarios. The results demonstrate that the proposed SH-DTI method achieves advanced performance in both quantitative and qualitative analyses of DTI. Moreover, it exhibits remarkable generalization capabilities across different acquisition schemes, centers, and scanners, ensuring its broad applicability in diverse settings.
RESUMO
The interplay between personality traits and impulsivity has long been a central theme in psychology and psychiatry. However, the potential association between Greed Personality Traits (GPT) and impulsivity, encompassing both trait and state impulsivity and future time perspective, remains largely unexplored. To address these issues, we employed questionnaires and an inter-temporal choice task to estimate corresponding trait/state impulsivity and collected multi-modal neuroimaging data (resting-state functional imaging: n = 430; diffusion-weighted imaging: n = 426; task-related functional imaging: n = 53) to investigate the underlying microstructural and functional substrates. Behavioral analyses revealed that GPT mediated the association between time perspective (e.g., present fatalism) and trait impulsivity (e.g., motor impulsivity). Functional imaging analyses further identified that brain activation strengths and patterns related to delay length, particularly in the dorsomedial prefrontal cortex, superior parietal lobule, and cerebellum, were associated with GPT. Moreover, individuals with similar levels of greed exhibited analogous spontaneous brain activity patterns, predominantly in the Default Mode Network (DMN), Fronto-Parietal Network (FPN), and Visual Network (VIS). Diffusion imaging analysis observed specific microstructural characteristics in the spinocerebellar/pontocerebellar fasciculus, internal/external capsule, and corona radiata that support the formation of GPT. Furthermore, the corresponding neural activation pattern, spontaneous neural activity pattern, and analogous functional couplings among the aforementioned brain regions mediated the relationships between time perspective and GPT and between GPT and motor impulsivity. These findings provide novel insights into the possible pathway such as time perspective â dispositional greed â impulsivity and uncover their underlying microstructural and functional substrates.
RESUMO
Indole is a microbial metabolite produced by the gut microbiota through the degradation of dietary tryptophan, known for its well-established anti-inflammatory and antioxidant properties. In this study, we collected fecal samples from mice fed a high-fat diet (HFD) and those on a standard diet (SD), then conducted 16S rRNA sequencing to analyze their gut microbiota. The analysis revealed distinct differences in the dominant bacterial species between the two groups, with a significant decrease in indole-producing probiotics in the HFD mice compared to the SD group. Then we administered oral indole treatment to male C57BL/6J mice with HFD-induced NAFLD and observed a significant improvement in hepatic steatosis and inflammation. Notably, indole alleviated the HFD-induced decline in serum Angiotensin-(1-7) [Ang-(1-7)] levels and Angiotensin-Converting Enzyme 2 (ACE2) expression. To further investigate the role of indole and ACE2 in NAFLD, we conducted experiments using ACE2 knockout (ACE2KO) mice that were also induced with HFD-induced NAFLD and treated with indole. Interestingly, the protective effects of indole were compromised in the absence of ACE2. In HepG2 cells, indole similarly stimulated ACE2 expression and, in an ACE2-dependent manner, reduced ROS generation, maintained mitochondrial membrane potential stability, and increased SIRT3 expression. In summary, our results highlight the formation of a biologically active gut-liver axis between the gut microbiota and the liver through the tryptophan metabolite indole, which mitigates NAFLD in an ACE2-dependent manner. Elevating dietary tryptophan and increasing indole levels may represent an effective approach for preventing and treating NAFLD.
Assuntos
Enzima de Conversão de Angiotensina 2 , Dieta Hiperlipídica , Microbioma Gastrointestinal , Indóis , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Animais , Enzima de Conversão de Angiotensina 2/metabolismo , Enzima de Conversão de Angiotensina 2/genética , Camundongos , Masculino , Indóis/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Humanos , Dieta Hiperlipídica/efeitos adversos , Camundongos Knockout , Fígado/metabolismo , Fígado/efeitos dos fármacos , Fragmentos de Peptídeos/metabolismo , Angiotensina IRESUMO
Pharyngeal endoderm cells undergo convergence and extension (C&E), which is essential for endoderm pouch formation and craniofacial development. Our previous work implicates Gα13/RhoA-mediated signaling in regulating this process, but the underlying mechanisms remain unclear. Here, we have used endoderm-specific transgenic and Gα13 mutant zebrafish to demonstrate that Gα13 plays a crucial role in pharyngeal endoderm C&E by regulating RhoA activation and E-cadherin expression. We showed that during C&E, endodermal cells gradually establish stable cell-cell contacts, acquire apical-basal polarity and undergo actomyosin-driven apical constriction, which are processes that require Gα13. Additionally, we found that Gα13-deficient embryos exhibit reduced E-cadherin expression, partially contributing to endoderm C&E defects. Notably, interfering with RhoA function disrupts spatial actomyosin activation without affecting E-cadherin expression. Collectively, our findings identify crucial cellular processes for pharyngeal endoderm C&E and reveal that Gα13 controls this through two independent pathways - modulating RhoA activation and regulating E-cadherin expression - thus unveiling intricate mechanisms governing pharyngeal endoderm morphogenesis.
Assuntos
Caderinas , Endoderma , Subunidades alfa G12-G13 de Proteínas de Ligação ao GTP , Regulação da Expressão Gênica no Desenvolvimento , Faringe , Proteínas de Peixe-Zebra , Peixe-Zebra , Proteína rhoA de Ligação ao GTP , Animais , Endoderma/metabolismo , Endoderma/embriologia , Endoderma/citologia , Caderinas/metabolismo , Caderinas/genética , Peixe-Zebra/embriologia , Peixe-Zebra/metabolismo , Peixe-Zebra/genética , Proteína rhoA de Ligação ao GTP/metabolismo , Proteína rhoA de Ligação ao GTP/genética , Proteínas de Peixe-Zebra/metabolismo , Proteínas de Peixe-Zebra/genética , Subunidades alfa G12-G13 de Proteínas de Ligação ao GTP/metabolismo , Subunidades alfa G12-G13 de Proteínas de Ligação ao GTP/genética , Faringe/embriologia , Faringe/metabolismo , Actomiosina/metabolismo , Transdução de Sinais , Morfogênese/genética , Polaridade Celular , Animais Geneticamente Modificados , Embrião não Mamífero/metabolismoRESUMO
Idiopathic pulmonary fibrosis (IPF) is a fatal respiratory disease characterized by chronic, progressive scarring of the lung parenchyma, leading to an irreversible decline in lung function. Apart from supportive care, there is currently no specific treatment available to reverse the disease. Based on the fact that tanshinone IIA (TAN) had an effect on protecting against TGF-ß1-induced fibrosis through the inhibition of Smad and non-Smad signal pathways to avoid myofibroblasts activation, this study reported the development of the inhalable tanshinone IIA-loaded chitosan-oligosaccharides-coated poly(lactic-co-glycolic acid) (PLGA) nanoparticles (CPN@TAN) for enhancing the pulmonary delivery of tanshinone IIA to treat pulmonary fibrosis. The CPN@TAN with a size of 206.5 nm exhibited excellent in vitro aerosol delivery characteristics, featuring a mass median aerodynamic diameter (MMAD) of 3.967 ± 0.025 µm and a fine particle fraction (FPF) of 70.516 ± 0.929%. Moreover, the nanoparticles showed good stability during atomization and enhanced the mucosal penetration capabilities. The results of confocal spectroscopy confirmed the potential of the nanoparticles as carriers that facilitated the uptake of drugs by NIH3T3, A549, and MH-S cells. Additionally, the nanoparticles demonstrated good in vitro biocompatibility. In a mouse model of bleomycin-induced pulmonary fibrosis, noninvasive inhalation of aerosol CPN@TAN greatly suppressed collagen formation and facilitated re-epithelialization of the destroyed alveolar epithelium without causing systemic toxicity compared with intravenous administration. Consequently, our noninvasive inhalation drug delivery technology based on polymers may represent a promising paradigm and open the door to overcoming the difficulties associated with managing pulmonary fibrosis.
RESUMO
Objectives: This study investigated the prevalence of suicidal ideation (SI) among Chinese medical students and its associated risk factors. Methods: A total of 6643 medical students (2383 males/4260 females) were recruited from a medical college in Hebei Province, China. Demographic data were collected via a self-administered questionnaire. The Childhood Trauma Questionnaire Short Form (CTQ-SF) was used to evaluate childhood maltreatment (CM), and the Adolescent Self-Rating Life Events Checklist (ASLEC) was used to evaluate the stressful life events. Suicidal ideation was assessed using the Beck Scale for Suicide Ideation (BSSI). Univariate and multivariate logistic regression models were used to analyze the factors affecting SI. Results: The prevalence of SI in medical students was 11.5% (763/6643). Multivariate logistic regression analysis revealed that SI was significantly associated with younger age, a female sex, being lovelorn, being introverted, experiencing CM during childhood, and experiencing stressful life events within the past 12 months. Of the five subtypes of CM, emotional abuse may have the strongest effect on SI (OR=2.76, 95% CI: 1.72-4.42). The joint effects of CM and stressful life events were significantly associated with an increased risk of SI (OR=5.39, 95% CI: 4.15-6.98). Conclusion: The prevalence of SI among medical students is high, and medical students who have experienced CM and stressful life events have a higher tendency towards SI. Screening for both CM and stressful life events may be an effective way of identifying individuals at high risk of SI.
RESUMO
[This corrects the article DOI: 10.1016/j.heliyon.2024.e30827.].
RESUMO
OBJECTIVES: To seek a triple combination of biomarkers for early diagnosis of chronic kidney disease-mineral and bone metabolic disorder and to explore the diagnostic efficacy of ß2-microglobulin, parathyroid hormone and blood urea nitrogen in chronic kidney disease-mineral and bone metabolic disorder. PARTICIPANTS: We collected medical records of 864 patients with chronic kidney disease (without direct contact with patients) and divided them into two groups based on the renal bone disease manifestations of all patients. PRIMARY AND SECONDARY OUTCOME MEASURES: There were 148 and 716 subjects in the Chronic kidney disease-mineral and bone metabolic disorder and the control groups, respectively. The aggregated data included basic information and various clinical laboratory indicators, such as blood lipid profile, antibody and electrolyte levels, along with renal function-related indicators. RESULTS: It was observed that most renal osteopathy occurs in the later stages of chronic kidney disease. In the comparison of two clinical laboratory indicators, 16 factors were selected for curve analysis and compared. We discovered that factors with high diagnostic values were ß2-microglobulin, parathyroid hormone and blood urea nitrogen. CONCLUSIONS: The triple combination of ß2-microglobulin+parathyroid hormone+blood urea nitrogen indicators can play the crucial role of a sensitive indicator for the early diagnosis of chronic kidney disease-mineral and bone metabolic disorder and in preventing or delaying the progress of chronic kidney disease-mineral and bone metabolic disorder.
Assuntos
Biomarcadores , Nitrogênio da Ureia Sanguínea , Distúrbio Mineral e Ósseo na Doença Renal Crônica , Hormônio Paratireóideo , Microglobulina beta-2 , Humanos , Estudos Transversais , Masculino , Feminino , Hormônio Paratireóideo/sangue , Pessoa de Meia-Idade , Distúrbio Mineral e Ósseo na Doença Renal Crônica/diagnóstico , Distúrbio Mineral e Ósseo na Doença Renal Crônica/sangue , China/epidemiologia , Biomarcadores/sangue , Microglobulina beta-2/sangue , Adulto , Idoso , Diagnóstico Precoce , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/diagnósticoRESUMO
Although targeted therapy has revolutionized oncotherapy, engineering a versatile oncotherapy nanoplatform integrating both diagnostics and therapeutics has always been an intractable challenge to overcome the limitations of monotherapy. Herein, a theranostics platform based on DI/MP-MB has successfully realized the fluorescence detection of disease marker miR-21 and the gene/photothermal/chemo triple synergetic cancer therapy, which can trace the tumor through photothermal and fluorescence dual-mode imaging and overcome the limitations of monotherapy to improve the treatment efficiency of tumors. DI/MP-MB was prepared by magnetic mesoporous silicon nanoparticles (M-MSNs) loaded with doxorubicin (Dox) and new indocyanine green (IR820), and subsequently coating polydopamine as a "gatekeeper", followed by the surface adsorbed with molecular beacons capable of targeting miR-21 for responsive imaging. Under the action of enhanced permeability retention and external magnetic field, DI/MP-MB were targeted and selectively accumulated in the tumor. MiR-21 MB hybridized with miR-21 to form a double strand, which led to the desorption of miR-21 MB from the polydopamine surface and the fluorescence recovery to realize gene silencing and fluorescence imaging for tracking the treatment process. Meanwhile, with the response to the near-infrared irradiation and the tumor's microacid environment, the outer layer polydopamine will decompose, releasing Dox and IR820 to realize chemotherapy and photothermal therapy. Finally, the ability of DI/MP-MB to efficiently suppress tumor growth was comprehensively assessed and validated both in vitro and in vivo. Noteworthily, the excellent anticancer efficiency by the synergistic effect of gene/photothermal/chemo triple therapy of DI/MP-MB makes it an ideal nanoplatform for tumor therapy and imaging.
Assuntos
Doxorrubicina , Indóis , MicroRNAs , Imagem Multimodal , Polímeros , Silício , Nanomedicina Teranóstica , Indóis/química , Polímeros/química , Silício/química , Humanos , Animais , Doxorrubicina/química , Doxorrubicina/farmacologia , Camundongos , Porosidade , Verde de Indocianina/química , Camundongos Nus , Camundongos Endogâmicos BALB C , Nanopartículas/química , Linhagem Celular Tumoral , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Imagem Óptica , Propriedades de SuperfícieRESUMO
Inflammatory pain is a chronic pain caused by peripheral tissue inflammation, seriously impacting the patient's life quality. Cinobufacini injection, as a traditional Chinese medicine injection preparation, shows excellent efficacy in anti-inflammatory and analgesic treatment in patients with advanced tumors. In this study, a novel analgesic peptide CI5 with anti-inflammatory and analgesic bio-functions that naturally presents in Cinobufacini injection and its regulatory mechanism are reported. Our results showed that the administration of CI5 significantly relieved the pain of mice in the acetic acid twisting analgesic model and formalin inflammatory pain model. Furthermore, CI5 effectively reduced the inflammatory cytokines (IL-6, TNF-α and IL-1ß) and inflammatory mediator (PGE2) expressions, and prevented the carrageenan-induced paw edema in mice. Further LC-MS/MS results showed the anti-inflammatory and analgesic bio-functions of CI5 depended on its interaction with the Rac-2 protein upstream of ERK1/2 and the inflammatory signaling pathway (ERK1/2/COX-2 axis). In summary, CI5, as a novel natural candidate identified from Cinobufacini injection, showed substantial clinical promise for inflammatory pain treatments.
Assuntos
Analgésicos , Anti-Inflamatórios , Ciclo-Oxigenase 2 , Edema , Inflamação , Dor , Animais , Analgésicos/uso terapêutico , Analgésicos/farmacologia , Analgésicos/administração & dosagem , Camundongos , Dor/tratamento farmacológico , Masculino , Inflamação/tratamento farmacológico , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/farmacologia , Ciclo-Oxigenase 2/metabolismo , Edema/tratamento farmacológico , Edema/induzido quimicamente , Venenos de Anfíbios/uso terapêutico , Venenos de Anfíbios/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Citocinas/metabolismo , Peptídeos/uso terapêutico , Peptídeos/farmacologia , Peptídeos/administração & dosagem , Humanos , Modelos Animais de Doenças , Carragenina , Mediadores da Inflamação/metabolismo , Dinoprostona/metabolismoRESUMO
Transformation represents one of the most important pathways for the horizontal transfer of antibiotic resistance genes (ARGs), which enables competent bacteria to acquire extracellular ARGs from the surrounding environment. Both heavy metals and irradiation have been demonstrated to influence the bacterial transformation process. However, the impact of ubiquitously occurring radioactive heavy metals on the transformation of ARGs remains largely unknown. Here, we showed that a representative radioactive nuclide, uranium (U), at environmental concentrations (0.005-5 mg/L), improved the transformation frequency of resistant plasmid pUC19 into Escherichia coli by 0.10-0.85-fold in a concentration-dependent manner. The enhanced ARGs transformation ability under U stress was demonstrated to be associated with reactive oxygen species (ROS) overproduction, membrane damage, and up-regulation of genes related to DNA uptake and recombination. Membrane permeability and ROS production were the predominant direct and indirect factors affecting transformation ability, respectively. Our findings provide valuable insight into the underlying mechanisms of the impacts of U on the ARGs transformation process and highlight concerns about the exacerbated spread of ARGs in radioactive heavy metal-contaminated ecosystems, especially in areas with nuclear activity or accidents.
Assuntos
Escherichia coli , Plasmídeos , Espécies Reativas de Oxigênio , Urânio , Urânio/toxicidade , Urânio/metabolismo , Escherichia coli/genética , Escherichia coli/efeitos dos fármacos , Escherichia coli/metabolismo , Escherichia coli/efeitos da radiação , Espécies Reativas de Oxigênio/metabolismo , Plasmídeos/genética , Resistência Microbiana a Medicamentos/genética , Farmacorresistência Bacteriana/genética , Transformação Bacteriana , Genes Bacterianos , Antibacterianos/farmacologiaRESUMO
Background: The relationship between type 2 diabetes mellitus (T2DM) and osteoporosis (OP) has been widely recognized in recent years, but the mechanism of interaction remains unknown. The aim of this study was to investigate the genetic features and signaling pathways that are shared between T2DM and OP. Methods: We analyzed the GSE76894 and GSE76895 datasets for T2DM and GSE56815 and GSE7429 for OP from the Gene Expression Omnibus (GEO) database to identify shared genes in T2DM and OP, and we constructed coexpression networks based on weighted gene coexpression network analysis (WGCNA). Shared genes were then further analyzed for functional pathway enrichment. We selected the best common biomarkers using the least absolute shrinkage and selection operator (LASSO) algorithm and validated the common biomarkers, followed by RT-PCR, immunofluorescence, Western blotting, and enzyme-linked immunosorbent assay (ELISA) to validate the expression of these hub genes in T2DM and OP mouse models and patients. Results: We found 8,506 and 2,030 DEGs in T2DM and OP, respectively. Four modules were identified as significant for T2DM and OP using WGCNA. A total of 19 genes overlapped with the strongest positive and negative modules of T2DM and OP. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed these genes may be involved in pantothenate and CoA biosynthesis and the glycosaminoglycan biosynthesis-chondroitin sulfate/dermatan sulfate and renin-angiotensin system signaling pathway. The LASSO algorithm calculates the six optimal common biomarkers. RT-PCR results show that LTB, TPBG, and VNN1 were upregulated in T2DM and OP. Immunofluorescence and Western blot show that VNN1 is upregulated in the pancreas and bones of T2DM model mice and osteoporosis model mice. Similarly, the level of VNN1 in the sera of patients with T2DM, OP, and T2DM and OP was higher than that in the healthy group. Conclusion: Based on the WGCNA and LASSO algorithms, we identified genes and pathways that were shared between T2DM and OP. Both pantothenate and CoA biosynthesis and the glycosaminoglycan biosynthesis-chondroitin sulfate/dermatan sulfate and renin-angiotensin systems may be associated with the pathogenesis of T2DM and OP. Moreover, VNN1 may be a potential diagnostic marker for patients with T2DM complicated by OP. This study provides a new perspective for the systematic study of possible mechanisms of combined OP and T2DM.
RESUMO
Radiotherapy is a widely used cancer treatment that utilizes powerful radiation to destroy cancer cells and shrink tumors. While radiation can be beneficial, it can also harm the healthy tissues surrounding the tumor. Recent research indicates that the microbiota, the collection of microorganisms in our body, may play a role in influencing the effectiveness and side effects of radiation therapy. Studies have shown that specific species of bacteria living in the stomach can influence the immune system's response to radiation, potentially increasing the effectiveness of treatment. Additionally, the microbiota may contribute to adverse effects like radiation-induced diarrhea. A potential strategy to enhance radiotherapy outcomes and capitalize on the microbiome involves using probiotics. Probiotics are living microorganisms that offer health benefits when consumed in sufficient quantities. Several studies have indicated that probiotics have the potential to alter the composition of the gut microbiota, resulting in an enhanced immune response to radiation therapy and consequently improving the efficacy of the treatment. It is important to note that radiation can disrupt the natural balance of gut bacteria, resulting in increased intestinal permeability and inflammatory conditions. These disruptions can lead to adverse effects such as diarrhea and damage to the intestinal lining. The emerging field of radiotherapy microbiome research offers a promising avenue for optimizing cancer treatment outcomes. This paper aims to provide an overview of the human microbiome and its role in augmenting radiation effectiveness while minimizing damage.
Assuntos
Microbioma Gastrointestinal , Neoplasias , Probióticos , Radioterapia , Humanos , Microbioma Gastrointestinal/efeitos da radiação , Neoplasias/radioterapia , Neoplasias/microbiologia , Neoplasias/imunologia , Neoplasias/terapia , Probióticos/uso terapêutico , Radioterapia/efeitos adversos , Radioterapia/métodos , Animais , Microbiota/efeitos da radiação , Lesões por Radiação/microbiologia , Lesões por Radiação/terapia , Lesões por Radiação/etiologia , Resultado do TratamentoRESUMO
BACKGROUND: The RNA interference (RNAi) efficiency of double-stranded RNA (dsRNA) delivery to insects by various methods is different and the reduced efficacy of feeding dsRNA is partly due to the presence of DNA/RNA non-specific endonuclease in the insect gut. However, the mechanism leading to the low RNAi efficiency of Nilaparvata lugens by feeding remains elusive. RESULTS: In this study, we identified a putatively DNA/RNA non-specific endonuclease gene in the N. lugens genome database that was highly expressed in the first nymphal instar and the midgut. Different expression levels of NldsRNase after feeding and injection suggested that NldsRNase might interfere with oral RNAi in N. lugens. A co-delivery RNAi strategy further revealed that the presence of NldsRNase reduces RNAi efficiency. In vitro dsRNA degradation experiments also showed that the stability of dsRNA was higher in a gut mixture from nymphs injected with dsNldsRNase. These results support the idea that the low oral RNAi response observed in N. lugens is likely due to the presence of NldsRNase. CONCLUSIONS: Our study provides insight into the differences in RNAi response between the injection and feeding of dsRNA in N. lugens and sheds light on the mechanisms underlying the reduced efficacy of RNAi via feeding. These findings may help to inform the development of more-effective RNAi-based strategies controlling N. lugens and other insect pests. © 2024 Society of Chemical Industry.
RESUMO
Tendinopathy is one of the most prevalent sports injury diseases in orthopedics. However, there is no effective treatment or medicine. Recently, the discovery of tendon stem cells (TSCs) provides a new perspective to find new therapeutic methods for Tendinopathy. Studies have shown that oxidative stress will inevitably cause TSCs injury during tendinopathy, but the mechanism has not been fully elucidated. Here, we report the oxidative damage of TSCs induced by H2O2 via ferroptosis, as well, treatment with H2O2 raised the proportion of mitochondria engulfed by autophagosomes in TSCs. The suppression of mitophagy by Mdivi-1 significantly attenuates the H2O2-induced ferroptosis in TSCs. Mechanically, H2O2 actives the cGAS-STING pathway, which can regulate the level of mitophagy. Interfering with cGAS could impair mitophagy and the classical ferroptotic events. In the rat model of tendinopathy, interference of cGAS could relieve tendon injury by inhibiting ferroptosis. Overall, these results provided novel implications to reveal the molecular mechanism of tendinopathy, by which pointed to cGAS as a potential therapeutic target for the treatment of tendinopathy.
Assuntos
Ferroptose , Peróxido de Hidrogênio , Proteínas de Membrana , Mitofagia , Nucleotidiltransferases , Estresse Oxidativo , Transdução de Sinais , Células-Tronco , Tendões , Mitofagia/efeitos dos fármacos , Animais , Nucleotidiltransferases/metabolismo , Proteínas de Membrana/metabolismo , Células-Tronco/metabolismo , Tendões/patologia , Tendões/metabolismo , Ratos , Peróxido de Hidrogênio/metabolismo , Humanos , Masculino , Ratos Sprague-Dawley , Tendinopatia/metabolismo , Tendinopatia/patologia , Células CultivadasRESUMO
Purpose: This study aims to assess the impact of death education on college students' sense of meaning in life and ability to cope with death. Method: A questionnaire survey was conducted among a randomly selected sample of 320 undergraduate students from a specific city. The survey, administered through the paper questionnaire, collected data on students' demographic characteristics, their awareness of death, and their demand for death education. Linear regression analysis was performed to identify factors influencing the demand for death education and assess its impact on college students' attitudes towards death, sense of meaning in life, and coping abilities. Results: The results revealed that participants' personality traits and family status significantly influenced their need for death education (P < .05). The overall score for death education needs among participants was (37.40±6.57). Notably, the statement "I think death education can help me understand death" received the highest mean rating (3.85), while the statement "I think death education will help me engage in nursing work in the future" received the lowest mean rating (3.55). Personal factors such as personality, family status, being an only child, and family experiences with serious illness were found to impact college students' demand for death education (P < .05). Post-death education, significant differences were observed in scores related to death fear and escape acceptance dimensions (P < .05). Moreover, there were statistically significant improvements in students' sense of meaning in life, quality of life, and life goals following death education (P < .05). Additionally, all dimensions of death coping ability showed higher scores after death education (P < .05). Factors such as current psychological state, being an only child, family experiences with serious illness, and attendance at funerals were found to be statistically significant in relation to college students' sense of meaning in life (P < .05). Multiple regression analysis indicated that the sense of meaning in life was influenced by the current psychological state and family experiences with serious illness (P < .05). Conclusion: The study highlights the importance of integrating death education into college curriculums to address students' fear of death and enhance their appreciation of life. Providing death education can help students develop a healthier perspective on death, improve their well-being, reduce avoidance attitudes towards death-related events, and strengthen their sense of meaning in life and ability to cope with death. These findings emphasize the need for educational institutions to implement comprehensive death education programs, considering individual factors such as personality and family background, and contribute to the development of effective educational policies and curricula.
RESUMO
Background: Snijders Blok-Campeau syndrome (SNIBCPS) is a rare genetic disorder characterized by facial abnormalities, hypotonia, macrocephaly, and global developmental delay (GDD) caused by mutations in CHD3 gene. There is limited information on SNIBCPS and few studies on its pathogenic gene CHD3. Methods: We utilized whole-exome sequencing, in vitro minigene splicing assay analysis, and construction of protein models to validate the suspected pathogenic mutation. In addition, the PubMed database was searched using the keywords "Snijders Blok-Campeau syndrome," "CHD3," or "SNIBCPS" to summarize the gene mutations and clinical phenotypic characteristics of children with SNIBCPS. Results: We identified a non-frameshift variant c.3592_c.3606delGCCAAGAGAAAGATG, a splice site variant c.1708-1G>T, and two missense variants, c. 2954G>C (p.Arg985Pro) and c.3371C>T (p.A1124V), in CHD3 variants with SNIBCPS. Importantly, the c.3592_c.3606delGCCAAGAGAAAGATG, c.1708-1G>T, and c.3371C > T (p.A1124V) loci were not reported, and the children in this study also had phenotypic features of unibrow, transverse palmar creases, tracheal bronchus, and hypomelanosis of Ito (HI). The c.1708-1G>T classical splicing mutation leads to abnormal shearing of mRNA, forming a truncated protein that ultimately affects gene function. Conclusion: Our findings have expanded the spectrum of genetic variants and clinical features in children with SNIBCPS. Splicing analysis of CHD3 is an important method to understand the pathogenesis of spliced cells.
RESUMO
Background: The "gut-islets axis" is an important endocrine signaling axis that regulates islets function by modulating the gut microbiota and endocrine metabolism within the gut. However, the specific mechanisms and roles of the intestine in islets regulation remain unclear. Recent studies investigated that exosomes derived from gut microbiota can transport signals to remotely regulate islets ß-cell function, suggesting the possibility of novel signaling pathways mediated by gut exosomes in the regulation of the "gut-islet axis.". Methods: The exosomes were isolated from the intestinal enteroendocrine cell-line STC-1cells culture supernatants treated with palmitate acid (PA) or BSA. Metabolic stress models were established by separately subjecting MIN6 cells to PA stimulation and feeding mice with a high-fat diet. Intervention with exosomes in vitro and in vivo to assess the biological effects of exosomes on islets ß cells under metabolic stress. The Mas receptor antagonist A779 and ACE2ko mice were used to evaluate the role of exosomal ACE2. Results: We found ACE2, a molecule that plays a crucial role in the regulation of islets function, is abundantly expressed in exosomes derived from STC-1 under physiological normal condition (NCEO). These exosomes cannot only be taken up by ß-cells in vitro but also selectively transported to the islets in vivo. Following intervention with NCEXO, both Min6 cells in a lipotoxic environment and mice on a high-fat diet exhibited significant improvements in islets ß-cell function and ß-cell mass. Further investigations demonstrated that these protective effects are attributed to exosomal ACE2, as ACE2 inhibits NLRP3 inflammasome activation and reduces ß-cell pyroptosis. Conclusion: ACE2-enriched exosomes from the gut can selectively target islets, subsequently inhibiting NLRP3 inflammasome activation and ß cell pyroptosis, thereby restoring islets ß cell function under metabolic stress. This study provides novel insights into therapeutic strategies for the prevention and treatment of obesity and diabetes.
Assuntos
Enzima de Conversão de Angiotensina 2 , Exossomos , Inflamassomos , Células Secretoras de Insulina , Proteína 3 que Contém Domínio de Pirina da Família NLR , Piroptose , Animais , Masculino , Camundongos , Enzima de Conversão de Angiotensina 2/metabolismo , Enzima de Conversão de Angiotensina 2/farmacologia , Linhagem Celular , Dieta Hiperlipídica , Células Enteroendócrinas/efeitos dos fármacos , Células Enteroendócrinas/metabolismo , Exossomos/química , Exossomos/metabolismo , Inflamassomos/metabolismo , Inflamassomos/efeitos dos fármacos , Células Secretoras de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/metabolismo , Intestino Delgado , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Piroptose/efeitos dos fármacos , Piroptose/fisiologiaRESUMO
BACKGROUND: Fragile X syndrome (FXS) is a genetic condition associated with increased risk for social anxiety and avoidance. Using functional near-infrared spectroscopy (fNIRS), we previously demonstrated aberrant neural activity responding to faces in young girls with FXS cross-sectionally. Here, we tested the hypothesis that abnormalities in neural activation and sensitization would increase with age in 65 girls with FXS (ages 6-16 years) relative to an age-matched control group of 52 girls who had comparable cognitive function and clinical symptoms. METHODS: fNIRS data were collected at 2 time points (mean [SD] = 2.8 [0.6] years apart) during a face processing task. Linear mixed-effect models examined longitudinal neural profiles in girls with FXS and control participants. Correlational analysis was performed to examine associations between neural sensitization (increasing neural response to repeated stimuli) and clinical ratings. RESULTS: In the FXS group, 24 participants had 1 fNIRS scan, and 32 had 2 scans. In the control group, 28 participants had 1 fNIRS scan, and 22 had 2 scans. Brain activations in the superior frontal gyrus were higher in girls with FXS than control participants at both time points. Neural sensitization also increased in girls with FXS at a higher rate than control participants in the superior frontal gyrus when responding to upright faces. For the FXS group, sensitization in the superior frontal gyrus positively correlated with longitudinal increases in anxiety and social avoidance scores. CONCLUSIONS: Girls with FXS show increasingly abnormal neural activation and sensitization responding to faces over time. Aberrant neural sensitization in girls with FXS is associated with longitudinal changes in anxiety and social skills.
RESUMO
BACKGROUND: Early life exposure to organophosphate (OP) pesticides is linked with adverse neurodevelopment and brain function in children. However, we have limited knowledge of how these exposures affect functional connectivity, a measure of interaction between brain regions. To address this gap, we examined the association between early life OP pesticide exposure and functional connectivity in adolescents. METHODS: We administered functional near-infrared spectroscopy (fNIRS) to 291 young adults with measured prenatal or childhood dialkylphosphates (DAPs) in the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) study, a longitudinal study of women recruited during pregnancy and their offspring. We measured DAPs in urinary samples collected from mothers during pregnancy (13 and 26 weeks) and children in early life (ages 6 months, 1, 2, 3, and 5 years). Youth underwent fNIRS while they performed executive function and semantic language tasks during their 18-year-old visit. We used covariate-adjusted regression models to estimate the associations of prenatal and childhood DAPs with functional connectivity between the frontal, temporal, and parietal regions, and a mediation model to examine the role of functional connectivity in the relationship between DAPs and task performance. RESULTS: We observed null associations of prenatal and childhood DAP concentrations and functional connectivity for the entire sample. However, when we looked for sex differences, we observed an association between childhood DAPs and functional connectivity for the right interior frontal and premotor cortex after correcting for the false discovery rate, among males, but not females. In addition, functional connectivity appeared to mediate an inverse association between DAPs and working memory accuracy among males. CONCLUSION: In CHAMACOS, a secondary analysis showed that adolescent males with elevated childhood OP pesticide exposure may have altered brain regional connectivity. This altered neurofunctional pattern in males may partially mediate working memory impairment associated with childhood DAP exposure.