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1.
BMC Psychol ; 12(1): 286, 2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38778400

RESUMEN

BACKGROUND: Mothers of children with autism reported higher levels of anxiety than mothers of typical children. This study revealed the relationship between parent-child conflict, children's problem behavior, parenting stress, and maternal anxiety from the perspective of the relationship within the family. METHODS: The State-Trait Anxiety Inventory (STAI) and Caregiver Strain Questionnaire (CGSQ) were used to measure maternal anxiety and parenting stress respectively from 102 mothers of children with autism. We also collected information on parent-child relationships and children's problem behaviors by using the Child-Parent Relationship Scale (CPRS) and Conners Parent Symptom Questionnaire (PSQ). RESULTS: Parent-child conflict positively predicted state and trait anxiety in mothers of children with autism. The severity of children's psychosomatic disorders fully mediated the positive association between parent-child conflict and state-trait anxiety in mothers of children with autism. Parenting stress significantly moderated the impact of parent-child conflict on maternal state anxiety and trait anxiety. CONCLUSION: In the case of children with autism spectrum disorders, parent-child conflict can directly affect maternal anxiety levels, especially when mothers have low levels of parenting stress. Parent-child conflict can also affect children's problem behaviors and thus indirectly affect maternal anxiety. Therefore, this study is of great significance for the alleviation of anxiety of mothers of autistic children and the family intervention for the early rehabilitation of autistic children.


Asunto(s)
Ansiedad , Madres , Estrés Psicológico , Humanos , Femenino , Ansiedad/psicología , Madres/psicología , Masculino , Adulto , Niño , Estrés Psicológico/psicología , Responsabilidad Parental/psicología , Preescolar , Trastorno Autístico/psicología , China , Encuestas y Cuestionarios , Relaciones Madre-Hijo/psicología , Relaciones Padres-Hijo , Problema de Conducta/psicología , Persona de Mediana Edad , Pueblos del Este de Asia
2.
Insects ; 15(4)2024 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-38667371

RESUMEN

Genome editing provides novel opportunities for the precise genome engineering of diverse organisms. Significant progress has been made in the development of genome-editing tools for Bombyx mori (B. mori) in recent years. Among these, CRISPR/Cas9, which is currently the most commonly used system in lepidopteran insects, recognizes NGG protospacer adjacent motif (PAM) sequences within the target locus. However, Cas9 lacks the ability to target all gene loci in B. mori, indicating the need for Cas9 variants with a larger editing range. In this study, we developed a high-throughput screening platform to validate Cas9 variants at all possible recognizable and editable PAM sites for target sequences in B. mori. This platform enabled us to identify PAM sites that can be recognized by both xCas9 3.7 and SpCas9-NG variants in B. mori and to assess their editing efficiency. Cas9 shows PAM sites every 13 base pairs in the genome, whereas xCas9 3.7 and SpCas9-NG have an average distance of 3.4 and 3.6 base pairs, respectively, between two specific targeting sites. Combining the two Cas9 variants could significantly expand the targeting range of the genome, accelerate research on the B. mori genome, and extend the high-throughput rapid screening platform to other insects, particularly those lacking suitable NGG PAM sequences.

3.
Antioxidants (Basel) ; 13(4)2024 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-38671870

RESUMEN

Dry eye disease (DED) is a multifactorial condition affecting the ocular surface. It is characterized by loss of tear film homeostasis and accompanied by ocular symptoms that may potentially result in damage to the ocular surface and even vision loss. Unmodifiable risk factors for DED mainly include aging, hormonal changes, and lifestyle issues such as reduced sleep duration, increased screen exposure, smoking, and ethanol consumption. As its prevalence continues to rise, DED has garnered considerable attention, prompting the exploration of potential new therapeutic targets. Recent studies have found that when the production of ROS exceeds the capacity of the antioxidant defense system on the ocular surface, oxidative stress ensues, leading to cellular apoptosis and further oxidative damage. These events can exacerbate inflammation and cellular stress responses, further increasing ROS levels and promoting a vicious cycle of oxidative stress in DED. Therefore, given the central role of reactive oxygen species in the vicious cycle of inflammation in DED, strategies involving antioxidants have emerged as a novel approach for its treatment. This review aims to enhance our understanding of the intricate relationship between oxidative stress and DED, thereby providing directions to explore innovative therapeutic approaches for this complex ocular disorder.

4.
Ocul Surf ; 32: 154-165, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38490475

RESUMEN

Meibomian gland dysfunction (MGD) is a chronic abnormality of the Meibomian glands (MGs) that is recognized as the leading cause of evaporative dry eye worldwide. Despite its prevalence, however, the pathophysiology of MGD remains elusive, and effective disease management continues to be a challenge. In the past 50 years, different models have been developed to illustrate the pathophysiological nature of MGD and the underlying disease mechanisms. An understanding of these models is crucial if researchers are to select an appropriate model to address specific questions related to MGD and to develop new treatments. Here, we summarize the various models of MGD, discuss their applications and limitations, and provide perspectives for future studies in the field.


Asunto(s)
Disfunción de la Glándula de Meibomio , Glándulas Tarsales , Disfunción de la Glándula de Meibomio/fisiopatología , Disfunción de la Glándula de Meibomio/metabolismo , Disfunción de la Glándula de Meibomio/terapia , Humanos , Glándulas Tarsales/fisiopatología , Glándulas Tarsales/metabolismo , Animales , Lágrimas/metabolismo , Lágrimas/fisiología , Síndromes de Ojo Seco/fisiopatología , Síndromes de Ojo Seco/metabolismo , Modelos Animales de Enfermedad
5.
Comput Struct Biotechnol J ; 23: 1051-1064, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38455068

RESUMEN

Gastric cancer (GC) poses a significant health challenge worldwide, necessitating the identification of predictive biomarkers to improve prognosis. Dysregulated lipid metabolism is a well-recognized hallmark of tumorigenesis, prompting investigation into apolipoproteins (APOs). In this study, we focused on apolipoprotein D (APOD) following comprehensive analyses of APOs in pan-cancer. Utilizing data from the TCGA-STAD and GSE62254 cohorts, we elucidated associations between APOD expression and multiple facets of GC, including prognosis, tumor microenvironment (TME), cancer biomarkers, mutations, and immunotherapy response, and identified potential anti-GC drugs. Single-cell analyses and immunohistochemical staining confirmed APOD expression in fibroblasts within the GC microenvironment. Additionally, we independently validated the prognostic significance of APOD in the ZN-GC cohort. Our comprehensive analyses revealed that high APOD expression in GC patients was notably associated with unfavorable clinical outcomes, reduced microsatellite instability and tumor mutation burden, alterations in the TME, and diminished response to immunotherapy. These findings provide valuable insights into the potential prognostic and therapeutic implications of APOD in GC.

6.
Int J Biol Macromol ; 265(Pt 2): 130845, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38503376

RESUMEN

Endometrial fibrosis leads to the destruction of endometrial function and affects reproductive performance. However, mechanisms underlying the development of endometrial fibrosis in sheep remain unclear. We use transcriptomic, proteomic, and metabolomic studies to reveal the formation mechanisms of endometrial fibrosis. The results showed that the fibrotic endometrial tissue phenotype presented fewer glands, accompanied by collagen deposition. Transcriptomic results indicated alterations in genes associated with the synthesis and degradation of extracellular matrix components, which alter metabolite homeostasis, especially in glycerophospholipid metabolism. Moreover, differentially expressed metabolites may play regulatory roles in key metabolic processes during fibrogenesis, including protein digestion and absorption, and amino acid synthesis. Affected by the aberrant genes, protein levels related to the extracellular matrix components were altered. In addition, based on Kyoto Encyclopedia of Genes and Genomes analysis of differentially expressed genes, metabolites and proteins, amino acid biosynthesis, glutathione, glycerophospholipid, arginine and proline metabolism, and cell adhesion are closely associated with fibrogenesis. Finally, we analyzed the dynamic changes in serum differential metabolites at different time points during fibrosis. Taken together, fibrosis development is related to metabolic obstacles in extracellular matrix synthesis and degradation triggered by disturbed gene and protein levels.


Asunto(s)
Multiómica , Proteómica , Animales , Ovinos , Matriz Extracelular/genética , Matriz Extracelular/metabolismo , Fibrosis , Transcriptoma , Glicerofosfolípidos/metabolismo , Aminoácidos/metabolismo
7.
Psychol Res Behav Manag ; 17: 1283-1294, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38524289

RESUMEN

Background: It is well known that parents play an important role in the family, particularly the mental health literacy of parents is essential for the growth and development of children. As the parents of children with special needs, they are facing more difficulties and psychological pressure, resulted in more mental health problems. Purpose: The current study examined the effect of social support on mental health literacy, and its underlying mechanisms regarding the mediating role of coping styles and moderating role of social comparison. Methods: Using a cross-sectional design, 165 parents of children with special needs (22-67 years old, M=37.72, SD=8.78) participated in the study. The general information questionnaire, Mental Health Literacy Scale (MHLS), Social Support Rating Scale, Simplified Coping Style Questionnaire, and Social Comparison Orientation Scale were used. Results: We found that objective support positively predicted the mental health literacy, positive coping style played a mediating role between objective support and mental health literacy. In addition, the relationship between objective support and positive coping styles was moderated by social comparisons; for lower levels of opinion social comparison, the effect of objective support on positive coping styles was significantly stronger. Conclusion: We revealed the underlying mechanisms between social support and mental health literacy. The present study has profound implications for mental health literacy services for parents who have children with special needs.

8.
Heart Vessels ; 2024 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-38507055

RESUMEN

BACKGROUND: This study was conducted to investigate the incidence of deep venous thrombosis (DVT), outcomes and its characteristics in patients with chronic heart failure (CHF) in a retrospective setting. OUTCOMES: Patients died of cardiac shock or acute exacerbation of heart failure (HF), admitted to intensive care unit (ICU) due to acute exacerbation of HF, patients decided to withdraw treatment and return home due to acute exacerbation of HF. METHODS: From January 2015 to June 2022, we admitted 359 patients diagnosed with CHF, and lower limb ultrasonography was performed for the examination of DVT after admission. The incidence of DVT was recorded and patients with known risk factors of VTE were identified and excluded after incidence of DVT was calculated. Patients' clinical data were then collected. RESULTS: The occurrence of DVT was 10.0% (36/359), as calf intramuscular vein thrombosis was the main constitution (n = 28, 75%). DVT patients with other factors (carcinoma, surgery, stroke, previous history of DVT) constituted a considerable part (33.3%, 12/36). Age, history of Diabetes Mellitus (DM), levels of DDi (D-Dimer), levels of alanine transferase (ALT) and left ventricular end-diastolic diameter (LVEDd) were independent predictors or risk factors of DVT in CHF patients, while chronic kidney disease (CKD) stage 1-4, white blood cell (WBC) and direct oral anticoagulant (DOAC) were protective factors. Incidence of DVT was correlated with a poor outcome of CHF patients (Pearson Chi-Square test, Value 19.612, P < 0.001). CONCLUSIONS: In this retrospective study, incidence of DVT was found to be relatively high among hospitalized CHF patients, while patients with DVT was associated with a poor prognosis.

9.
Fa Yi Xue Za Zhi ; 40(1): 59-63, 2024 Feb 25.
Artículo en Inglés, Chino | MEDLINE | ID: mdl-38500462

RESUMEN

Important forensic diagnostic indicators of sudden death in coronary atherosclerotic heart disease, such as acute or chronic myocardial ischemic changes, sometimes make it difficult to locate the ischemic site due to the short death process, the lack of tissue reaction time. In some cases, the deceased died of sudden death on the first-episode, resulting in difficulty for medical examiners to make an accurate diagnosis. However, clinical studies on coronary instability plaque revealed the key role of coronary spasm and thrombosis caused by their lesions in sudden coronary death process. This paper mainly summarizes the pathological characteristics of unstable coronary plaque based on clinical medical research, including plaque rupture, plaque erosion and calcified nodules, as well as the influencing factors leading to plaque instability, and briefly describes the research progress and technique of the atherosclerotic plaques, in order to improve the study on the mechanism of sudden coronary death and improve the accuracy of the forensic diagnosis of sudden coronary death by diagnosing different pathologic states of coronary atherosclerotic plaques.


Asunto(s)
Enfermedad de la Arteria Coronaria , Trombosis Coronaria , Placa Aterosclerótica , Humanos , Placa Aterosclerótica/complicaciones , Placa Aterosclerótica/patología , Trombosis Coronaria/complicaciones , Trombosis Coronaria/patología , Factores de Riesgo , Enfermedad de la Arteria Coronaria/complicaciones , Muerte Súbita Cardíaca/etiología , Muerte Súbita Cardíaca/patología , Vasos Coronarios/diagnóstico por imagen , Vasos Coronarios/patología
10.
Artículo en Inglés | MEDLINE | ID: mdl-38421849

RESUMEN

Graph learning is widely applied to process various complex data structures (e.g., time series) in different domains. Due to multidimensional observations and the requirement for accurate data representation, time series are usually represented in the form of multilabels. Accurately classifying multilabel time series can provide support for personalized predictions and risk assessments. It requires effectively capturing complex label relevance and overcoming imbalanced label distributions of multilabel time series. However, the existing methods are unable to model label relevance for multilabel time series or fail to fully exploit it. In addition, the existing multilabel classification balancing strategies suffer from limitations, such as disregarding label relevance, information loss, and sampling bias. This article proposes a dynamic graph attention autoencoder-based multitask (DGAAE-MT) learning framework for multilabel time series classification. It can fully and accurately model label relevance for each instance by using a dynamic graph attention-based graph autoencoder to improve multilabel classification accuracy. DGAAE-MT employs a dual-sampling strategy and cooperative training approach to improve the classification accuracy of low-frequency classes while maintaining the classification accuracy of high-frequency and mid-frequency classes. It avoids information loss and sampling bias. DGAAE-MT achieves a mean average precision (mAP) of 0.955 and an F1 score of 0.978 on a mixed medical time series dataset. It outperforms state-of-the-art works in the past two years.

11.
Front Plant Sci ; 15: 1333207, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38344186

RESUMEN

With the rapid development of the livestock industry, finding new sources of feed has become a critical issue that needs to be addressed urgently. China is one of the top five sunflower producers in the world and generates a massive amount of sunflower stalks annually, yet this resource has not been effectively utilized. Therefore, in order to tap into the potential of sunflower stalks for animal feed, it is essential to explore and develop efficient methods for their utilization.In this study, various proportions of alfalfa and sunflower straw were co-ensiled with the following mixing ratios: 0:10, 2:8, 4:6, 5:5, 6:4, and 8:2, denoted as A0S10, A2S8, A4S6, A5S5, A6S4, and A8S2, respectively. The nutrient composition, fermentation quality, microbial quantity, microbial diversity, and broad-spectrum metabolomics on the 60th day were assessed. The results showed that the treatment groups with more sunflower straw added (A2S8, A4S6) could start fermentation earlier. On the first day of fermentation, Weissella spp.dominated overwhelmingly in these two groups. At the same time, in the early stage of fermentation, the pH in these two groups dropped rapidly, which could effectively reduce the loss of nutrients in the early stage of fermentation.In the later fermentation period, a declining trend in acetic acid levels was observed in A0S10, A2S8, and A4S6, while no butyric acid production was detected in A0S10 and A2S8 throughout the process. In A4S6, butyric acid production was observed only after 30 days of fermentation. From the perspective of metabolites, compared with sunflower ensiling alone, many bioactive substances such as flavonoids, alkaloids, and terpenes are upregulated in mixed ensiling.

12.
Phytomedicine ; 125: 155374, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38301302

RESUMEN

BACKGROUND: In China, Gardenia jasminoides Ellis (GJE) has a longstanding history of application. The Ministry of Health has listed it as one of the first pharmaceutical or food resources. In ethnic, traditional, and folk medicine, GJE has been used to treat fever and cold and relieve nervous anxiety. Recent studies have confirmed the significant efficacy of GJE for treating central nervous system (CNS) disorders, including Alzheimer's disease, Parkinson's disease, and major depressive disorder; however, GJE has not been systematically evaluated. PURPOSE: This research systematically summarizes global studies on the use of GJE for treating CNS disorders and explores the potential applications and underlying mechanisms via intestinal flora analysis and network pharmacology, aiming to establish a scientific basis for innovative CNS disorder treatment with GJE. METHODS: The PRISMA guidelines were used, and electronic databases such as the Web of Science, PubMed, and China National Knowledge Infrastructure were searched using the following search terms: "Gardenia jasminoides Ellis" with "central nervous system disease," "neuroprotection," "Alzheimer's disease," "Parkinson's disease," "ischemic stroke," "Epilepsy," and "major depressive disorder." The published literature up to September 2023 was searched to obtain relevant information on the application of GJE for treating CNS disorders. RESULTS: There has been an increase in research on the material formulation and mechanisms of action of GJE for treating CNS disorders, with marked effects on CNS disorder treatment in different countries and regions. We summarized the research results related to the role of GJE in vitro and in vivo via multitargeted interventions in response to the complex mechanisms of action of CNS disorders. CONCLUSION: We systematically reviewed the research progress on traditional treatment for GJE and preclinical mechanisms of CNS disorders and explored the potential of optimizing network pharmacology strategies and intestinal flora analysis to elucidate the mechanisms of action of GJE. The remarkable therapeutic efficacy of GJE, an important resource in traditional medicine, has been well documented in the literature, highlighting its significant medicinal potential.


Asunto(s)
Enfermedad de Alzheimer , Trastorno Depresivo Mayor , Gardenia , Enfermedad de Parkinson , Humanos , Gardenia/química , Enfermedad de Alzheimer/tratamiento farmacológico , Neuroprotección
13.
J Ethnopharmacol ; 325: 117810, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38266948

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Vine Tea (VT, Ampelopsis grossedentata), boasts a venerable tradition in China, with a recorded consumption history exceeding 1200 years. Predominantly utilized by ethnic groups in southwest China, this herbal tea is celebrated for its multifaceted therapeutic attributes. Traditionally, VT has been employed to alleviate heat and remove toxins, exhibit anti-inflammatory properties, soothe sore throats, lower blood pressure, and fortify bones and muscles. In the realm of functional foods derived from plant resources, VT has garnered attention for its potential in crafting anti-fatigue beverages or foods, attributed to its promising efficacy and minimal side effects. Currently, in accordance with the Food Safety Standards set forth by the Monitoring and Evaluation Department of the National Health and Family Planning Commission in China, VT serves as a raw material in various beverages. AIM OF THE STUDY: VT has an anti-fatigue or similar effect in folk. However, the underlying molecular mechanisms contributing to VT's anti-fatigue effects remain elusive. This study endeavors to investigate the influence of Vine Tea Aqueous Extract (VTE) on fatigue mitigation and to elucidate its operative mechanisms, with the objective of developing VTE as a functional beverage. MATERIALS AND METHODS: The preparation of VTE involved heat extraction and freeze-drying processes, followed by the identification of its metabolites using UPLC-QTOF-MS to ascertain the chemical composition of VTE. A fatigue model was established using a forced swimming test in mice. Potential molecular targets were identified through network pharmacology, transcriptome analysis, and molecular docking. Furthermore, RT-PCR and Western blot techniques were employed to assess mRNA and protein expressions related to the AMPK and FoxO pathways. RESULTS: VTE significantly prolonged the duration of swimming time in an exhaustive swimming test in a dose-dependent manner, while simultaneously reducing the concentrations of blood lactic acid (LA), lactate dehydrogenase (LDH), serum urea nitrogen (SUN), and creatine kinase (CK). Notably, the performance of the high-dose VTE group surpassed that of the well-recognized ginsenoside. VTE demonstrated a regulatory effect akin to ginsenoside on the AMPK energy metabolism pathway and induced downregulation in the expression of Gadd45α, Cdkn1a, FOXO1, and Fbxo32 genes, suggesting an enhancement in skeletal muscle mass. These findings indicate that VTE can improve energy metabolism and muscle mass concurrently. CONCLUSIONS: VTE exhibits significant anti-fatigue effects, and its mechanism is intricately linked to the modulation of the AMPK and FoxO pathways. Crucially, no caffeine or other addictive substances with known side effects were detected in VTE. Consequently, vine tea shows substantial promise as a natural resource for the development of anti-fatigue beverages within the food industry.


Asunto(s)
Ampelopsis , Ginsenósidos , Ratones , Animales , Ampelopsis/química , Ampelopsis/metabolismo , Proteínas Quinasas Activadas por AMP/metabolismo , Ginsenósidos/uso terapéutico , Simulación del Acoplamiento Molecular , Fatiga/tratamiento farmacológico , , Músculos
14.
Artículo en Inglés | MEDLINE | ID: mdl-38261491

RESUMEN

Cognitive computing explores brain mechanisms and develops brain-like computing models for cognitive processes. EEG measures brain activity, and EEG classification identifies patterns using machine learning algorithms. Combining EEG classification with cognitive computing offers insights into cognitive processes, brainmachine interfaces, and cognitive state monitoring. We propose (DreamCatcher Network) DCNet, a self-supervised learning method for diagnosing sleep disorders using EEG. DCNet autonomously learns comprehensive representations through contrast learning, reducing annotation time. The training process involves feature learning, classification, time-series contrast learning, and data enhancement. Experimental results on the Sleep-EDF dataset achieved 81.28% average accuracy. Validation on the HAR dataset showed model efficiency and scalability, with 92.51% accuracy on the test set. DCNet has the potential to revolutionize sleep disorder diagnosis and enhance the development of cognitive computing-enabled smart healthcare systems.

15.
Clin Interv Aging ; 19: 109-118, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38250175

RESUMEN

Purpose: To explore the predictive value of nutritional risk for all-cause death and functional outcomes among elderly acute stroke patients. Patients and Methods: A total of 479 elderly acute stroke patients were enrolled in this study. The nutritional risk of patients was screened by the GNRI and NRS-2002. The primary outcome was all-cause death, and the secondary outcome was poor prognosis defined as a modified Rankin Scale (mRS) score ≥3. Results: Based on the NRS-2002, patients with nutritional risk had a higher risk of all-cause death at 3 months (adjusted OR: 3.642, 95% CI 1.046~12.689) and at 3 years (adjusted OR: 2.266, 95% CI 1.259~4.076) and a higher risk of adverse functional outcomes at 3 months (adjusted OR: 2.748, 95% CI 1.518~4.972. Based on the GNRI, compared to those without nutritional risk, patients with mild malnutrition also had a higher risk of all-cause death at 3 months (adjusted OR: 7.186, 95% CI 1.550~33.315) and at 3 years (adjusted OR: 2.255, 95% CI 1.211~4.199) and a higher risk of adverse functional outcomes at 3 months (adjusted OR: 1.947, 95% CI 1.030~3.680), so patients with moderate and severe malnutrition had a higher risk of all-cause death at 3 months (adjusted OR: 6.535, 95% CI 1.380~30.945) and at 3 years (adjusted OR: 2.498, 95% CI 1.301~4.799) and a higher risk of adverse functional outcomes at 3 months (adjusted OR: 2.213, 95% CI 1.144~4.279). Conclusion: Nutritional risk increases the risk of poor short-term and long-term outcomes in elderly patients with acute stroke. For elderly stroke patients, we should pay attention to early nutritional risk screening, and effective intervention should be provided to improve the prognosis of such patients.


Asunto(s)
Desnutrición , Pirimidinas , Accidente Cerebrovascular , Estirenos , Tiofenos , Anciano , Humanos , Estudios de Seguimiento , China
16.
Int J Mol Sci ; 25(2)2024 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-38255806

RESUMEN

Microtia-atresia is a rare type of congenital craniofacial malformation causing severe damage to the appearance and hearing ability of affected individuals. The genetic factors associated with microtia-atresia have not yet been determined. The AMER1 gene has been identified as potentially pathogenic for microtia-atresia in two twin families. An amer1 mosaic knockdown zebrafish model was constructed using CRISPR/Cas9. The phenotype and the development process of cranial neural crest cells of the knockdown zebrafish were examined. Components of the Wnt/ß-catenin pathway were examined by qPCR, Western blotting, and immunofluorescence assay. IWR-1-endo, a reversible inhibitor of the Wnt/ß-catenin pathway, was applied to rescue the abnormal phenotype. The present study showed that the development of mandibular cartilage in zebrafish was severely compromised by amer1 knockdown using CRISPR/Cas9. Specifically, amer1 knockdown was found to affect the proliferation and apoptosis of cranial neural crest cells, as well as their differentiation to chondrocytes. Mechanistically, amer1 exerted an antagonistic effect on the Wnt/ß-catenin pathway. The application of IWR-1-endo could partially rescue the abnormal phenotype. We demonstrated that amer1 was essential for the craniofacial development of zebrafish by interacting with the Wnt/ß-catenin pathway. These findings provide important insight into the role of amer1 in zebrafish mandibular development and the pathology of microtia-atresia caused by AMER1 gene mutations in humans.


Asunto(s)
Microtia Congénita , Imidas , Quinolinas , Pez Cebra , Animales , Apoptosis/genética , beta Catenina/genética , Pez Cebra/genética
17.
Genome Res ; 34(1): 134-144, 2024 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-38191205

RESUMEN

Large-scale genetic mutant libraries are powerful approaches to interrogating genotype-phenotype correlations and identifying genes responsible for certain environmental stimuli, both of which are the central goal of life science study. We produced the first large-scale CRISPR-Cas9-induced library in a nonmodel multicellular organism, Bombyx mori We developed a piggyBac-delivered binary genome editing strategy, which can simultaneously meet the requirements of mixed microinjection, efficient multipurpose genetic operation, and preservation of growth-defect lines. We constructed a single-guide RNA (sgRNA) plasmid library containing 92,917 sgRNAs targeting promoters and exons of 14,645 protein-coding genes, established 1726 transgenic sgRNA lines following microinjection of 66,650 embryos, and generated 300 mutant lines with diverse phenotypic changes. Phenomic characterization of mutant lines identified a large set of genes responsible for visual phenotypic or economically valuable trait changes. Next, we performed pooled context-specific positive screens for tolerance to environmental pollutant cadmium exposure, and identified KWMTBOMO12902 as a strong candidate gene for breeding applications in sericulture industry. Collectively, our results provide a novel and versatile approach for functional B. mori genomics, as well as a powerful resource for identifying the potential of key candidate genes for improving various economic traits. This study also shows the effectiveness, practicality, and convenience of large-scale mutant libraries in other nonmodel organisms.


Asunto(s)
Bombyx , Animales , Bombyx/genética , ARN Guía de Sistemas CRISPR-Cas , Mutagénesis , Edición Génica/métodos , Animales Modificados Genéticamente/genética , Sistemas CRISPR-Cas
18.
Int J Mol Sci ; 24(23)2023 Dec 02.
Artículo en Inglés | MEDLINE | ID: mdl-38069381

RESUMEN

Ardisiae Crenatae Radix is an ethnic medicinal herb with good anti-inflammatory activity. Ardisiacrispin B is one of the main components in Ardisiae Crenatae Radix extract, with a content of up to 16.27%, and it may be one of the pharmacological components through which Ardisiae Crenatae Radix exerts anti-inflammatory activity. At present, reports on ardisiacrispin B mainly focus on anti-tumor effects, and there have been no reports on anti-inflammatory activities. As a triterpenoid saponin, due to its large molecular weight and complex structure, the composition of substances that function in the body may include other forms after metabolism, in addition to compounds with original structures. Exploring the anti-inflammatory effects on the prototypes and metabolites of the compound may provide a more comprehensive response to the characteristics of ardisiacrispin B's anti-inflammatory action. In this study, ardisiacrispin B was analyzed for metabolites to explore its metabolic processes in vivo. Subsequently, the anti-inflammatory effects of the prototypes and metabolites were further analyzed through network pharmacology, with the expectation of discovering the signaling metabolic pathways through which they may act. Finally, the anti-inflammatory effects of ardisiacrispin B in vitro and the effects on key signaling pathways at the protein level were explored. The results of this study showed that the isolated compounds were confirmed to be ardisiacrispin B. After the metabolite analysis, a total of 26 metabolites were analyzed, and the metabolism process in rats mainly involves oxidation, dehydration, glucuronide conjugation, and others. Speculation as to the anti-inflammatory molecular mechanisms of the prototypes and metabolites of ardisiacrispin B revealed that it may exert its anti-inflammatory effects mainly by affecting the PI3K-AKT pathway. Further anti-inflammatory mechanisms demonstrated that ardisiacrispin B had a good anti-inflammatory effect on LPS-induced RAW264.7 cells and a strong inhibitory effect on NO, TNF-α, and IL-1ß release in cells. Furthermore, it had significant inhibitory effects on the expression of PI3K, P-PI3K, AKT, and P-AKT. This study supplements the gaps in the knowledge on the in vivo metabolic process of ardisiacrispin B and explores its anti-inflammatory mechanism, providing an experimental basis for the development and utilization of pentacyclic triterpenoids.


Asunto(s)
Proteínas Proto-Oncogénicas c-akt , Saponinas , Ratas , Animales , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Farmacología en Red , Saponinas/química , Antiinflamatorios/farmacología , Antiinflamatorios/química , Simulación del Acoplamiento Molecular
19.
BMC Pediatr ; 23(1): 623, 2023 12 09.
Artículo en Inglés | MEDLINE | ID: mdl-38071296

RESUMEN

INTRODUCTION: In recent years, intracardiac electrocardiogram (IC-ECG) technology has been widely used for epicutaneo-cava catheter (ECC) placement and has shown many potential advantages. However, evidence about the quantitative changes, effectiveness, and safety of IC-ECG for lower extremity ECC is sparse. This study aimed to explore the quantitative changes in IC-ECG for lower extremity ECC and determine its effectiveness and safety. METHODS: A retrospective study was conducted on 303 premature infants who underwent successful IC-ECG-guided lower extremity ECC placement between January 2019 and December 2021. All patients underwent chest X-ray postoperatively to verify the position of the catheter tip. The amplitudes of the surface electrocardiogram and IC-ECG QRS waves and the difference between the two amplitudes were measured. The effectiveness (matching rate between IC-ECG and chest X-ray) and safety (incidence of catheter-related complications) of IC-ECG for lower extremity ECC were evaluated. RESULTS: The matching rate between IC-ECG and chest X-ray was 95.0%. When the catheter tip was optimally positioned, the QRS amplitude of the IC-ECG was 0.85 ± 0.56 mv higher than that of the surface electrocardiogram. The overall incidence of catheter-related complications was 10.6%. The actual ECC insertion length was associated with a noticeably increased risk of catheter-related complications. CONCLUSIONS: This study suggests that IC-ECG is an effective and safe method by observing the dynamic changes in both QRS complexes and P wave to locate the tip of lower extremity ECC in preterm infants. Our findings would facilitate the application of IC-ECG for ECC localization.


Asunto(s)
Cateterismo Venoso Central , Cateterismo Periférico , Catéteres Venosos Centrales , Lactante , Humanos , Recién Nacido , Recien Nacido Prematuro , Estudios Retrospectivos , Cateterismo Venoso Central/efectos adversos , Cateterismo Periférico/efectos adversos , Electrocardiografía/métodos , Catéteres
20.
Brain Circ ; 9(3): 154-161, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38020957

RESUMEN

Social cognition guides social behavior. Subjects with proper social cognition should be able to: (1) have reasonable social motivation, (2) recognize other people and infer their intentions, and (3) weigh social hierarchies and other values. The choice of appropriate behavioral paradigms enables the use of rodents to study social behavior disorders in humans, thus enabling research to go deeper into neural mechanisms. This paper reviews commonly used rodent behavioral paradigms in studies of social behavior disorders. We focused specifically on sorting out ways to transfer the study of human social behavior to rodents through behavioral paradigms.

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