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Major depressive disorder (MDD) is a prevalent and devastating mental illness. To date, the diagnosis of MDD is largely dependent on clinical interviews and questionnaires and still lacks a reliable biomarker. DNA methylation has a stable and reversible nature and is likely associated with the course and therapeutic efficacy of complex diseases, which may play an important role in the etiology of a disease. Here, we identified and validated a DNA methylation biomarker for MDD from four independent cohorts of the Chinese Han population. First, we integrated the analysis of the DNA methylation microarray (n = 80) and RNA expression microarray data (n = 40) and identified BICD2 as the top-ranked gene. In the replication phase, we employed the Sequenom MassARRAY method to confirm the DNA hypermethylation change in a large sample size (n = 1,346) and used the methylation-sensitive restriction enzymes and a quantitative PCR approach (MSE-qPCR) and qPCR method to confirm the correlation between DNA hypermethylation and mRNA down-regulation of BICD2 (n = 60). The results were replicated in the peripheral blood of mice with depressive-like behaviors, while in the hippocampus of mice, Bicd2 showed DNA hypomethylation and mRNA/protein up-regulation. Hippocampal Bicd2 knockdown demonstrates antidepressant action in the chronic unpredictable mild stress (CUMS) mouse model of depression, which may be mediated by increased BDNF expression. Our study identified a potential DNA methylation biomarker and investigated its functional implications, which could be exploited to improve the diagnosis and treatment of MDD.
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Metilação de DNA , Transtorno Depressivo Maior , Hipocampo , Proteínas Associadas aos Microtúbulos , Animais , DNA/metabolismo , Transtorno Depressivo Maior/sangue , Transtorno Depressivo Maior/genética , Modelos Animais de Doenças , Regulação para Baixo , Técnicas de Silenciamento de Genes , Marcadores Genéticos , Hipocampo/metabolismo , Humanos , Camundongos , Proteínas Associadas aos Microtúbulos/genética , RNA Mensageiro/metabolismo , Estresse Psicológico/genéticaRESUMO
The multidrug and toxic compound extrusion (MATE) proteins are coding by a secondary transporter gene family, and have been identified to participate in the modulation of organic acid exudation for aluminum (Al) resistance. The soybean variety Glycine max "Tamba" (TBS) exhibits high Al tolerance. The expression patterns of MATE genes in response to Al stress in TBS and their specific functions in the context of Al stress remain elusive. In this study, 124 MATE genes were identified from the soybean genome. The RNA-Seq results revealed significant upregulation of GmMATE13 and GmMATE75 in TBS upon exposure to high-dose Al3+ treatment and both genes demonstrated sequence homology to citrate transporters of other plants. Subcellular localization showed that both proteins were located in the cell membrane. Transgenic complementation experiments of Arabidopsis mutants, atmate, with GmMATE13 or GmMATE75 genes enhanced the Al tolerance of the plant due to citrate secretion. Taken together, this study identified GmMATE13 and GmMATE75 as citrate transporter genes in TBS, which could improve citrate secretion and enhance Al tolerance. Our findings provide genetic resources for the development of plant varieties that are resistant to Al toxicity.
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Alumínio , Arabidopsis , Alumínio/toxicidade , Glycine max/genética , Arabidopsis/genética , Membrana Celular , CitratosRESUMO
AIMS: This study aims to examine the prevalence of anxiety symptoms and identify predictors of anxiety among pregnant women with gestational diabetes mellitus and their partners and explore the mediating role of marital satisfaction between maternal and paternal anxiety. DESIGN: A cross-sectional study was conducted in Guangzhou, China, from July 2021 to May 2022. METHODS: A total of 306 dyads of pregnant women with gestational diabetes mellitus and their partners completed the State-Trait Anxiety Inventory, Locke-Wallace Marital Adjustment Test and the socio-demographic and clinical data sheet. RESULTS: The prevalence of anxiety symptoms was 32.4% and 36.6% in pregnant women with gestational diabetes mellitus and their partners, respectively. The predictors of maternal anxiety were paternal anxiety, maternal marital satisfaction, maternal monthly salary, fasting glucose value and 1-h glucose value. By contrast, the predictors of paternal anxiety were maternal anxiety, paternal marital satisfaction and paternal monthly salary. Moreover, the relationship between maternal and paternal anxiety was mediated by marital satisfaction. CONCLUSIONS: The anxiety symptoms of pregnant women with gestational diabetes mellitus and their partners influence each other, and this relationship was mediated by marital satisfaction. Every couple should be screened for anxiety symptoms and treated as a team rather than focusing solely on the pregnant woman.
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Diabetes Gestacional , Gestantes , Masculino , Gravidez , Feminino , Humanos , Diabetes Gestacional/epidemiologia , Estudos Transversais , Ansiedade/epidemiologia , Glucose , Satisfação PessoalRESUMO
AIMS/BACKGROUND: Coping with gestational diabetes mellitus (GDM) presents significant challenges for pregnant women and their partners, which may result in elevated prenatal depression symptoms. However, research has predominantly centred on pregnant women with GDM, with little involvement of their partners. To understand their dyadic interactions, it is imperative to involve GDM couples in the study. This study aims to examine the interplay between dyadic coping and prenatal depression symptoms among GDM couples and to explore the possible mediating role of marital satisfaction. DESIGN/METHOD: A cross-sectional study was conducted in Guangzhou, China. A total of 400 couples completed the Dyadic Coping Inventory, Locke-Wallace Marital Adjustment Scale, Edinburgh Postnatal Depression Scale, and sociodemographic data sheet. The actor-partner interdependence mediation model was utilised for dyadic data analysis. RESULTS: Overall, 13.0% of pregnant women with GDM and 8.3% of partners experienced elevated prenatal depression symptoms. Dyadic coping was directly or indirectly related to their own and partners' prenatal depression symptoms in GDM couples, with marital satisfaction acting as a mediator. Specifically, positive dyadic coping was associated with lower prenatal depression symptoms, while negative dyadic coping exhibited an opposite relationship. CONCLUSION: The prevalence of elevated prenatal depression symptoms was high in GDM couples. It is important to view pregnant women with GDM and their partners as a dyad of a transactional system in prenatal clinical care. Couple-centred interventions targeting to enhance positive dyadic coping and mitigate negative dyadic coping might be beneficial to prevent and alleviate prenatal depression symptoms.
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It is recommended that pregnant women be physically active to promote maternal and child health. This study aimed to explore the prevalence of physical inactivity and its modifiable predictors in the three trimesters in Chinese pregnant women. Four hundred forty-four pregnant women completed the Pregnant Physical Activity Questionnaire in the first, second, and third trimesters. The prevalence of physical inactivity reached its highest (66.2%) in the first trimester and lowest (19.4%) in the second trimester. Pregnant women with inadequate physical activity knowledge and low self-efficacy were at higher risk for physical inactivity. Monitoring physical inactivity could be incorporated into antenatal care and start from the first trimester. Prenatal care professionals should take action to increase pregnant women's physical activity self-efficacy and knowledge to enhance their physical activity.
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Gestantes , Comportamento Sedentário , Criança , Gravidez , Feminino , Humanos , Terceiro Trimestre da Gravidez , Segundo Trimestre da Gravidez , Trimestres da GravidezRESUMO
Physical activity during pregnancy has numerous health benefits for the woman and the foetus. The current study investigated physical activity engagement and its predictors among pregnant Chinese women during the first trimester. A total of 687 pregnant women completed the Pregnancy Physical Activity Questionnaire. Bivariate and multivariate logistic regression were used to analyse the data. The current physical activity guidelines were not met by 64.3% of respondents. Women with higher levels of physical activity self-efficacy (aOR = 0.96; 95% CI: 0.92-0.99) and social support (aOR = 0.95; 95% CI: 0.94-0.97) had lower odds of not meeting the current physical activity guidelines. Women who were aged < 35 years (aOR = 1.85; 95% CI: 1.02-3.34), had lower education (aOR = 1.63; 95% CI: 1.04-2.55), were primiparous (aOR = 11.03; 95% CI: 6.98-17.44), were unsure of their delivery mode (aOR = 2.32; 95% CI: 1.95-5.64), and those who had higher levels of pregnancy-associated discomfort (aOR = 1.10; 95% CI: 1.03-1.19) had higher odds of not meeting the current physical activity guidelines. The current study suggests that healthcare professionals should assess physical activity engagement during routine antenatal care and increase efforts to strengthen pregnant women's self-efficacy and social support to promote physical activity engagement during the first trimester.
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Exercício Físico , Gestantes , Feminino , Gravidez , Humanos , Estudos Transversais , Primeiro Trimestre da Gravidez , Paridade , ChinaRESUMO
OBJECTIVE: To evaluate the association between remnant cholesterol (remnant-C) and intracranial atherosclerotic disease (ICAD) in the Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS). METHODS: We studied 1,564 participants with data on lipid profiles and high-resolution vessel wall MRI (VWMRI) from the ARIC-NCS. Remnant-C was computed as total cholesterol minus high-density lipoprotein cholesterol minus low-density lipoprotein cholesterol (LDL-C). The primary outcomes were the presence of intracranial plaques and luminal stenosis. Contributors were separated into four different groups based on remnant-C (22 mg/dL) and LDL-C (100 mg/dL) levels to investigate the function of remnant-C vs. LDL-C on ICAD. Multivariable logistic regression models were utilized to estimate the correlation among the discordant/concordant remnant-C and LDL-C, and ICAD. RESULTS: A total of 1,564 participants were included (age 76.2 ± 5.3). After multivariable adjustment, log remnant-C was correlated with greater ICAD risk [odds ratio (OR) 1.36, 95% confidence interval (CI) 1.01 to 1.83]. The lower remnant-C/higher LDL-C group and the higher remnant-C/lower LDL-C group manifested a 1.53-fold (95% CI 1.06 to 2.20) and 1.52-fold (95% CI 1.08 to 2.14) greater risk of ICAD, relative to those having lower remnant-C/low LDL-C. Additionally, remnant-C ≥ 22 mg/dL distinguished participants at a greater risk of the presence of any stenosis compared to those at lower levels, even in participants with optimal levels of LDL-C. CONCLUSIONS: Elevated levels of remnant-C were connected to ICAD independent of LDL-C and traditional risk factors. The mechanisms of remnant-C association with ICAD probably offer insight into preventive risk-factor of ischemic stroke.
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Aterosclerose , Arteriosclerose Intracraniana , Humanos , Idoso , Idoso de 80 Anos ou mais , LDL-Colesterol , Constrição Patológica , Colesterol , Fatores de Risco , Aterosclerose/diagnóstico por imagem , Aterosclerose/epidemiologia , Arteriosclerose Intracraniana/diagnóstico por imagem , Arteriosclerose Intracraniana/epidemiologiaRESUMO
AIM: This review aimed to appraise clinical guidelines about exercise for women with gestational diabetes mellitus and summarize consensus and inconsistent recommendations. BACKGROUND: Exercise is an effective non-pharmacological therapeutic for gestational diabetes mellitus, but the variety of relevant clinical practice guidelines is confusing for healthcare professionals. DESIGN: This is a systematic review of clinical practice guidelines. DATA SOURCES: Websites of guideline development institutions, eight literature databases and organizations of obstetricians, gynaecologists, midwives, and medical sports associations were searched for guidelines published from January 2011 to October 2021. REVIEW METHODS: Two reviewers independently extracted recommendations. Four reviewers assessed guideline quality using the AGREE II instrument independently. RESULTS: Fifteen guidelines were included. All women with diabetes are recommended to exercise during pregnancy. The consistent recommendations were for pre-exercise screening, for 30 min per exercise session on 5 days of the week or every day after meals, exercise at moderate intensity, using aerobic and resistance exercise, and walking. The main non-consistent recommendations included warning signs for women on insulin during exercise, minimum duration per session, intensity assessment, duration and frequency of sessions for strengthening and flexibility exercise and detailed physical activity giving birth. CONCLUSIONS: Guidelines strongly support pregnant women with diabetes to exercise regularly. Research is needed to make non-consistent recommendations clear.
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Diabetes Gestacional , Gravidez , Feminino , Humanos , Diabetes Gestacional/terapia , Gestantes , Exercício Físico , Terapia por ExercícioRESUMO
OBJECTIVE: This study aimed to explore the prevalence of prenatal depression and to determine the dyadic relationship between perceived stress, marital satisfaction, and prenatal depression in pregnant women with gestational diabetes mellitus (GDM) and their partners. BACKGROUND: GDM during pregnancy is a very stressful event for couples. However, previous studies have largely focused on pregnant women, with few including their partners. METHODS: A cross-sectional study was conducted in Guangzhou, China, from 30 July to 2 December 2021. Three hundred fourteen couples with GDM completed the Perceived Stress Scale, Locke-Wallace Marital Adjustment Scale, and Edinburgh Postnatal Depression Scale. Dyadic analysis was conducted using the actor-partner interdependence mediation model. RESULTS: The prevalence of depressive symptoms was 13.4% in pregnant women with GDM and 8.3% in their partners. Regarding the actor effects, perceived stress was positively associated with prenatal depression in pregnant women with GDM and their partners, respectively, and marital satisfaction acted as a mediating role. Regarding the partner effects, paternal perceived stress was negatively associated with maternal marital satisfaction, and maternal marital satisfaction mediated the association between paternal perceived stress and maternal prenatal depression. CONCLUSIONS: Dyadic effects of perceived stress, marital satisfaction, and prenatal depression exist in couples with GDM.
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A preparative supercritical fluid chromatography method for the separation of Piper kadsura obtained five phenylamide compounds, which had the same structural skeleton, but changed in the number and position of methoxyl substituents. To improve the separation selectivity of these structural analogues, silica, phenyl, and chiral stationary phases were screened. Only through the combination of Chiral C and phenyl columns could the separation of the five phenylamides be solved. The two-step strategy using preparative supercritical fluid chromatography presented good orthogonality that ensured the purity of the phenylamides. Then, an ultra-high-performance supercritical fluid chromatography hyphened tandem mass spectrometry method was developed, and the fragmentation pattern of phenylamides was summarized. It mainly cleaved in the amide bond to produce the fragment ion, which could help to judge the substituent positions. Twenty-eight possible molecular weights of hydroxyl and methoxyl substituted phenylamides were calculated and screened. Nine compounds were extracted in three [M + H]+ ions at m/z 284.13, 314.13, and 344.13, including five purified compounds and the other four positional or trans-cis phenylamide isomers in low content. The methods developed in this research were useful in the separation and characterization of phenylamide analogues.
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Amidas , Cromatografia com Fluido Supercrítico/métodos , Piper/química , Espectrometria de Massas em Tandem/métodos , Amidas/análise , Amidas/química , Amidas/isolamento & purificação , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas ChinesasRESUMO
Glucose is the main circulating energy substrate for the adult brain. Owing to the high energy demand of nerve cells, glucose is actively oxidized to produce ATP and has a synergistic effect with mitochondria in metabolic pathways. The dysfunction of glucose metabolism inevitably disturbs the normal functioning of neurons, which is widely observed in neurodegenerative disease. Understanding the mechanisms of metabolic adaptation during disease progression has become a major focus of research, and interventions in these processes may relieve the neurons from degenerative stress. In this review, we highlight evidence of mitochondrial dysfunction, decreased glucose uptake, and diminished glucose metabolism in different neurodegeneration models such as Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD). We also discuss how hypoxia, a metabolic reprogramming strategy linked to glucose metabolism in tumor cells and normal brain cells, and summarize the evidence for hypoxia as a putative therapy for general neurodegenerative disease.
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Suscetibilidade a Doenças , Glucose/metabolismo , Doenças Neurodegenerativas/etiologia , Doenças Neurodegenerativas/metabolismo , Animais , Encéfalo/metabolismo , Metabolismo dos Carboidratos/efeitos dos fármacos , Reprogramação Celular/efeitos dos fármacos , Gerenciamento Clínico , Metabolismo Energético , Humanos , Hipóxia/tratamento farmacológico , Hipóxia/metabolismo , Terapia de Alvo Molecular , Doenças Neurodegenerativas/diagnóstico , Doenças Neurodegenerativas/terapia , Neurônios/metabolismo , Oxirredução , Espécies Reativas de Oxigênio/metabolismoRESUMO
Faithful representation of sound envelopes in primary auditory cortex (A1) is vital for temporal processing and perception of natural sounds. However, the emergence of cortical temporal processing mechanisms during development remains poorly understood. Although cortical inhibition has been proposed to play an important role in this process, direct in-vivo evidence has been lacking. Using loose-patch recordings in rat A1 immediately after hearing onset, we found that stimulus-following ability in fast-spiking neurons was significantly better than in regular-spiking (RS) neurons. In-vivo whole-cell recordings of RS neurons revealed that inhibition in the developing A1 demonstrated much weaker adaptation to repetitive stimuli than in adult A1. Furthermore, inhibitory synaptic inputs were of longer duration than observed in vitro and in adults. Early in development, overlap of the prolonged inhibition evoked by 2 closely following stimuli disrupted the classical temporal sequence between excitation and inhibition, resulting in slower following capacity. During maturation, inhibitory duration gradually shortened accompanied by an improving temporal following ability of RS neurons. Both inhibitory duration and stimulus-following ability demonstrated exposure-based plasticity. These results demonstrate the role of inhibition in setting the pace for experience-dependent maturation of temporal processing in the auditory cortex.
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Potenciais de Ação/fisiologia , Córtex Auditivo/citologia , Córtex Auditivo/crescimento & desenvolvimento , Inibição Neural/fisiologia , Neurônios/fisiologia , Estimulação Acústica , Fatores Etários , Animais , Animais Recém-Nascidos , Impedância Elétrica , Neurônios/classificação , Técnicas de Patch-Clamp , Ratos , Ratos Sprague-Dawley , Fatores de TempoRESUMO
Our bioassays reviewed that antennae played crucial roles in the responses of maize weevil (Sitophilus zeamais) to food and sex volatiles. In order to identify the maize weevil odorant-binding protein (OBP) genes, we analyzed its antennal transcriptome. In total, 21,587,928 high-quality clean reads were obtained from RNA-seq, 52,206 unigenes were assembled, and 25,744 unigenes showed significant similarity ( E value < 10 -5 ) to known proteins in the NCBI nonredundant protein database. From those unigenes, we identified 41 candidate OBP proteins, which could be categorized into dimeric OBPs subfamily, minus-C OBPs subfamily, and classical OBPs subfamily. Phylogenic analysis indicated that most maize weevil OBPs were closely related to their orthologues in other beetles of the Superfamily Curculionoidea. We further investigated the expression profiles of those candidate OBP genes by quantitative real-time polymerase chain reaction. Twenty-six of forty-one maize weevil OBP genes were highly expressed in the antennae or other parts of the head. The rest were expressed in the legs, wings, or other tested tissues. The antennal transcriptomic data and candidate OBP genes described here provide a basis for the functional studies of the maize weevil chemical perception, which are potential novel targets for pest control strategies.
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Antenas de Artrópodes/metabolismo , Perfilação da Expressão Gênica , Receptores Odorantes/genética , Gorgulhos/genética , Animais , Expressão Gênica , Proteínas de Insetos/genética , Filogenia , Reação em Cadeia da Polimerase em Tempo Real/métodos , Receptores Odorantes/metabolismo , Gorgulhos/metabolismoRESUMO
Aluminum (Al) toxicity is one of the environmental stress factors that affects crop growth, development, and productivity. MYB transcription factors play crucial roles in responding to biotic or abiotic stresses. However, the roles of MYB transcription factors in Al tolerance have not been clearly elucidated. Here, we found that GmMYB183, a gene encoding a R2R3 MYB transcription factor, is involved in Al tolerance. Subcellular localization studies revealed that GmMYB183 protein is located in the nucleus, cytoplasm and cell membrane. Overexpression of GmMYB183 in Arabidopsis and soybean hairy roots enhanced plant tolerance towards Al stress compared to the wild type, with higher citrate secretion and less Al accumulation. Furthermore, we showed that GmMYB183 binds the GmMATE75 gene promoter encoding for a plasma-membrane-localized citrate transporter. Through a dual-luciferase reporter system and yeast one hybrid, the GmMYB183 protein was shown to directly activate the transcription of GmMATE75. Furthermore, the expression of GmMATE75 may depend on phosphorylation of Ser36 residues in GmMYB183 and two MYB sites in P3 segment of the GmMATE75 promoter. In conclusion, GmMYB183 conferred Al tolerance by promoting the secretion of citrate, which provides a scientific basis for further elucidating the mechanism of plant Al resistance.
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Alumínio , Arabidopsis , Regulação da Expressão Gênica de Plantas , Glycine max , Proteínas de Plantas , Regiões Promotoras Genéticas , Fatores de Transcrição , Alumínio/toxicidade , Alumínio/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Arabidopsis/efeitos dos fármacos , Glycine max/genética , Glycine max/metabolismo , Glycine max/efeitos dos fármacos , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regiões Promotoras Genéticas/genética , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/metabolismo , Estresse Fisiológico/genética , Estresse Fisiológico/efeitos dos fármacos , Raízes de Plantas/metabolismo , Raízes de Plantas/genética , Raízes de Plantas/efeitos dos fármacos , Proteínas de TransporteRESUMO
INTRODUCTION: Postpartum depression affects both mothers and fathers. This study aimed to examine the relationships between social support, parenting self-efficacy, and postpartum depression in Chinese mothers and fathers and assess the mediating effect of parenting self-efficacy using a dyadic perspective. METHODS: A cross-sectional study was implemented from December 2020 to July 2021 in Guangzhou, China, with 309 pairs of parents. The Edinburgh Postnatal Depression Scale, Social Support Rating Scale, Parenting Sense of Competence Scale-Efficacy subscale, and sociodemographic data sheet were completed by both parents. Dyadic analysis was conducted using the actor-partner interdependence mediation model. An actor effect is the relationship between variables within an individual, whereas a partner effect is the relationship between variables in the individual and the dyadic partner. RESULTS: In total, 20.7% of mothers and 11.7% of fathers had elevated postpartum depressive symptoms at 6 weeks postpartum. The model revealed 6 actor effects: social support was positively associated with parenting self-efficacy for mothers (ß, 0.39; 95% CI, 0.28-0.49) and fathers (ß, 0.39; 95% CI, 0.30-0.48) and negatively associated with postpartum depression for mothers (ß, -0.22; 95% CI, -0.32 to -0.12) and fathers (ß, -0.37; 95% CI, -0.48 to -0.26). Parenting self-efficacy was negatively associated with postpartum depression in mothers (ß, -0.41; 95% CI, -0.53 to -0.29) and fathers (ß, -0.24; 95% CI, -0.37 to -0.12). Maternal social support had a partner effect on paternal parenting self-efficacy (ß, 0.14; 95% CI, 0.04-0.24). Parenting self-efficacy mediated between social support and postpartum depression for both parents (mothers: ß, -0.16; 95% CI, -0.23 to -0.10; fathers: ß, -0.10; 95% CI, -0.16 to -0.05). DISCUSSION: Postpartum depression was a dyadic phenomenon. Increasing mother-centered social support has the potential to improve the parenting self-efficacy of both parents and reduce the likelihood of postpartum depression.
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Depressão Pós-Parto , Pai , Mães , Poder Familiar , Autoeficácia , Apoio Social , Humanos , Depressão Pós-Parto/psicologia , Feminino , Poder Familiar/psicologia , Estudos Transversais , Adulto , China , Masculino , Pai/psicologia , Mães/psicologia , Pais/psicologia , População do Leste AsiáticoRESUMO
AIMS: Incidence of acute mountain sickness (AMS) ranges from 40%-90%, with high-altitude cerebral edema (HACE) representing a life-threatening end stage of severe AMS. However, practical and convenient preventive strategies for HACE are lacking. Remote ischemic preconditioning (RIPC) has demonstrated preventive effects on ischemia- or hypoxia-induced cardiovascular and cerebrovascular diseases. This study aimed to investigate the potential molecular mechanism of HACE and the application of RIPC in preventing HACE onset. METHODS: A hypobaric hypoxia chamber was used to simulate a high-altitude environment of 7000 meters. Metabolomics and metabolic flux analysis were employed to assay metabolite levels. Transcriptomics and quantitative real-time PCR (q-PCR) were used to investigate gene expression levels. Immunofluorescence staining was performed on neurons to label cellular proteins. The fluorescent probes Mito-Dendra2, iATPSnFR1.0, and CMTMRos were used to observe mitochondria, ATP, and membrane potential in cultured neurons, respectively. TUNEL staining was performed to detect and quantify apoptotic cell death. Hematoxylin and eosin (H&E) staining was utilized to analyze pathological changes, such as tissue swelling in cerebral cortex samples. The Rotarod test was performed to assess motor coordination and balance in rats. Oxygen-glucose deprivation (OGD) of cultured cells was employed as an in vitro model to simulate the hypoxia and hypoglycemia induced by RIPC in animal experiments. RESULTS: We revealed a causative perturbation of glucose metabolism in the brain preceding cerebral edema. Ischemic preconditioning treatment significantly reprograms glucose metabolism, ameliorating cell apoptosis and hypoxia-induced energy deprivation. Notably, ischemic preconditioning improves mitochondrial membrane potential and ATP production through enhanced glucose-coupled mitochondrial metabolism. In vivo studies confirm that RIPC alleviates cerebral edema, reduces cell apoptosis induced by high-altitude hypoxia, and improves motor dysfunction resulting from cerebral edema. CONCLUSIONS: Our study elucidates the metabolic basis of HACE pathogenesis. This study provides a new strategy for preventing HACE that RIPC reduces brain edema through reprogramming metabolism, highlighting the potential of targeting metabolic reprogramming for neuroprotective interventions in neurological diseases caused by ischemia or hypoxia.
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Doença da Altitude , Edema Encefálico , Glucose , Precondicionamento Isquêmico , Ratos Sprague-Dawley , Animais , Edema Encefálico/prevenção & controle , Edema Encefálico/etiologia , Edema Encefálico/metabolismo , Glucose/metabolismo , Precondicionamento Isquêmico/métodos , Masculino , Doença da Altitude/prevenção & controle , Doença da Altitude/metabolismo , Ratos , Células Cultivadas , Neurônios/metabolismo , Neurônios/patologia , Apoptose/fisiologia , Reprogramação MetabólicaRESUMO
Purpose: To perform a meta-analysis of clinical trials comparing percutaneous microwave ablation (PMWA) guided by ultrasound with conventional thyroidectomy for the management of papillary thyroid microcarcinoma (PTMC), analyzing feasibility, safety, and long-term efficacy, and to provide clinical guidance for the treatment selection of PTMC. Methods: Embase, PubMed, Cochrane Library, Web of Science, CNKI, VIP Database, and Wanfang Database were systematically searched to identify clinical studies of PMWA or thyroidectomy for PTMC up to December 2023. The relevant data from the articles were extracted, and the data analysis was performed using RevMan 5.4 software. Results: A total of 442 articles were identified and subsequently screened based on the inclusion and exclusion criteria, 9 clinical studies involving a total of 1577 patients were included, with 788 patients in the PMWA group and 789 patients in the surgery group. Following data extraction and statistical analysis, in comparison to the surgery group, the PMWA group had shorter operation time [mean differences (MD) = -36.36; 95% CI -55.66 to -17.06; P = .0002], shorter hospital stay (MD = -3.93; 95% CI -5.55 to -2.30; P < .00001), less intraoperative bleeding (MD = -21.25; 95% CI -27.36 to -15.15; P < .00001), and lower hospital costs (MD = -1.00; 95% CI -1.33 to -0.66; P < .00001), all with statistical significance. The comparison of postoperative complications revealed a lower incidence of complications in the PMWA group compared to the surgery group [relative risk (RR) = 0.29; 95% CI 0.21 to 0.40; P < .00001], with statistical significance. Thyroid-related hormone analysis showed that the free triiodothyronine (MD = 0.61; 95% CI 0.33 to 0.90; P < .00001) and free thyroxine (MD = 1.81; 95% CI 0.94 to 2.68; P < .0001) levels in the PMWA group were higher than those in the traditional surgery group, while the levels of thyroid-stimulating hormone were lower than those in the traditional surgery group (MD = -7.63; 95% CI -10.25 to -5.01; P < .00001), with statistically significant differences, indicating that PMWA had a smaller impact on thyroid function. In 2 studies, there were no statistically significant disparities in postoperative recurrence or lymph node metastasis (LNM) between the 2 cohorts (RR = 0.70; 95% CI 0.33 to 1.50; P = .36). There were no statistically significant differences in physiological health score between different groups and different time points before and after treatment (P > .05); However, the mental component score and the total score of the Medical Outcomes Study (MOS) item short-form health survey were significantly elevated in the ablation group compared to the excision group post-treatment (P < .05). Conclusion: For patients with low-risk PTMC with definitive diagnosis and precise risk stratification, PMWA can be selected. PMWA treatment for patients with PTMC is comparable to conventional surgical treatment and has the advantages of minimal trauma, rapid recovery, no scarring, and fewer complications, which are superior to open surgery to a certain extent. For patients with ambiguous preoperative diagnosis and uncertainty regarding LNM status, surgical intervention is the optimal choice.
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Nasopharyngeal carcinoma (NPC) is a common head and neck malignancy, which is characterized by high incidence and aggression with poor diagnosis and limited therapeutic opportunity. The innovative strategy for achieving precise NPC active-targeting drug delivery has emerged as a prominent focus in clinical research. Here, a minimalist cancer cell membrane (CCM) shielded biomimetic nanoparticle (NP) was designed for NPC active-targeting therapy. Chemotherapeutant model drug doxorubicin (DOX) was loaded in polyamidoamine (PAMAM) dendrimer. The PAMAM/DOX (PD) NP was further shielded by human CNE-2 NPC CCM. Characterization results verified that the biomimetic PAMAM/DOX@CCM (abbreviated as PDC) NPs had satisfactory physical properties with high DOX-loading and excellent stability. Cell experiments demonstrated that the CNE-2 membrane-cloaked PDC NPs presented powerful cellular uptake in the sourcing cells by homologous targeting and adhesive interaction. Further in vivo results confirmed that this biomimetic nanoplatform had extended circulation and remarkable tumor-targeting capability, and the PDC NPs effectively suppressed the progression of CNE-2 tumors by systemic administration. This CCM-shielded biomimetic NP displayed a minimalist paradigm nanoplatform for precise NPC therapy, and the strategy of CCM-shielded biomimetic drug delivery system (DDS) has great potential for extensive cancer active-targeting therapy.
Assuntos
Materiais Biomiméticos , Membrana Celular , Doxorrubicina , Nanopartículas , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Humanos , Doxorrubicina/farmacologia , Doxorrubicina/química , Nanopartículas/química , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/patologia , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Membrana Celular/química , Membrana Celular/metabolismo , Membrana Celular/efeitos dos fármacos , Animais , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/patologia , Dendrímeros/química , Camundongos , Linhagem Celular Tumoral , Sistemas de Liberação de Medicamentos , Antibióticos Antineoplásicos/farmacologia , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/administração & dosagem , Proliferação de Células/efeitos dos fármacos , Camundongos Nus , Camundongos Endogâmicos BALB C , Biomimética , Tamanho da PartículaRESUMO
PURPOSE: We assessed the effects of tracheostomy timing (early vs. late) on outcomes among adult patients receiving mechanical ventilation. METHODS: PubMed, Embase, Web of Science and Cochrane Library were searched to identify relevant RCTs of tracheotomy timing on patients receiving mechanical ventilation. Two reviewers independently screened the literature, extracted data. Outcomes in patients with early tracheostomy and late tracheostomy groups were compared and analyzed. Meta-analysis was performed using Stata14.0 and RevMan 5.4 software. This study is registered with PROSPERO (CRD42022360319). RESULTS: Twenty-one RCTs were included in this Meta-analysis. The Meta-analysis indicated that early tracheotomy could significantly shorten the duration of mechanical ventilation (MD: -2.77; 95% CI -5.10~ -0.44; P = 0.02) and the length of ICU stay (MD: -6.36; 95% CI -9.84~ -2.88; P = 0.0003), but it did not significantly alter the all-cause mortality (RR 0.86; 95% CI 0.73~1.00; P = 0.06), the incidence of pneumonia (RR 0.86; 95% CI 0.74~1.01; P = 0.06), and length of hospital stay (MD: -3.24; 95% CI -7.99~ 1.52; P = 0.18). CONCLUSION: In patients requiring mechanical ventilation, the tracheostomy performed at an earlier stage may shorten the duration of mechanical ventilation and the length of ICU stay but cannot significantly decrease the all-cause mortality and incidence of pneumonia.
Assuntos
Tempo de Internação , Ensaios Clínicos Controlados Aleatórios como Assunto , Respiração Artificial , Traqueotomia , Humanos , Traqueotomia/efeitos adversos , Traqueotomia/métodos , Fatores de Tempo , Unidades de Terapia Intensiva , Traqueostomia/efeitos adversos , Traqueostomia/métodosRESUMO
PROBLEM: No studies have been conducted to examine the relationships between perceived stress, positive/negative dyadic coping, and prenatal depression symptoms in Chinese couples with gestational diabetes mellitus (GDM). BACKGROUND: GDM is a stressful event for pregnant women and their partners, which may result in clinically significant prenatal depression symptoms in couples. AIM: This study aims to examine the relationships and differences in perceived stress, positive/negative dyadic coping, and prenatal depression symptoms between Chinese pregnant women with GDM and their partners and to explore the mediating role of positive/negative dyadic coping. METHODS: A cross-sectional study was conducted in Guangzhou, China, from January to October 2021. 402 pairs of GDM couples completed the questionnaires, including the Edinburgh Postnatal Depression Scale, the Chinese version of the Dyadic Coping Inventory, and the Perceived Stress Scale. Dyadic data was analyzed using the actor-partner interdependence mediation model. FINDINGS: 37.6 % of pregnant women with GDM and 24.6 % of their partners experienced clinically significant prenatal depression symptoms. Depression symptoms in couples mutually influence each other. Perceived stress was directly or indirectly related to their and partners' prenatal depression symptoms in GDM couples, with negative dyadic coping acting as a mediator. Maternal negative dyadic coping was also a partner-mediator. DISCUSSION: The findings of the present study may provide healthcare professionals with a better understanding of the effect of the interpersonal interaction between the couples as a dyad on prenatal depression symptoms in Chinese context. CONCLUSION: There were intrapersonal and interpersonal associations among perceived stress, negative dyadic coping, and prenatal depression symptoms in pregnant women with GDM and their partners. It suggests a need for screening clinically significant prenatal depression symptoms and decreasing perceived stress and negative dyadic coping among couples with GDM with a focus on pregnant women with GDM.