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Pathogen type 3 secretion systems (T3SS) manipulate host cell pathways by directly delivering effector proteins into host cells. In Vibrio parahaemolyticus, the leading cause of bacterial seafood-borne diarrheal disease, we showed that a T3SS effector, VgpA, localizes to the host cell nucleolus where it binds Epstein-Barr virus nuclear antigen 1-binding protein 2 (EBP2). An amino acid substitution in VgpA (VgpAL10A ) did not alter its translocation to the nucleus but abolished the effector's capacity to interact with EBP2. VgpA-EBP2 interaction led to the re-localization of c-Myc to the nucleolus and increased cellular rRNA expression and proliferation of cultured cells. The VgpA-EBP2 interaction elevated EBP2's affinity for c-Myc and prolonged the oncoprotein's half-life. Studies in infant rabbits demonstrated that VgpA is translocated into intestinal epithelial cells, where it interacts with EBP2 and leads to nucleolar re-localization of c-Myc. Moreover, the in vivo VgpA-EBP2 interaction during infection led to proliferation of intestinal cells and heightened V. parahaemolyticus' colonization and virulence. These observations suggest that direct effector stimulation of a c-Myc controlled host cell growth program can contribute to pathogenesis.
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Proteínas Bacterianas/metabolismo , Nucléolo Celular/metabolismo , Proliferación Celular/fisiología , Proteínas Proto-Oncogénicas c-myc/metabolismo , Sistemas de Secreción Tipo III/metabolismo , Vibrio parahaemolyticus/metabolismo , Virulencia/fisiología , Animales , Células CACO-2 , Proteínas Portadoras/metabolismo , Línea Celular Tumoral , Células Epiteliales/metabolismo , Infecciones por Virus de Epstein-Barr/metabolismo , Antígenos Nucleares del Virus de Epstein-Barr/metabolismo , Regulación Bacteriana de la Expresión Génica/fisiología , Herpesvirus Humano 4/patogenicidad , Humanos , ARN Ribosómico/metabolismo , Proteínas de Unión al ARN/metabolismo , Conejos , Vibriosis/metabolismoRESUMEN
The cell-to-cell transmission of viral resistance is a potential mechanism for amplifying the interferon-induced antiviral response. In this study, we report that interferon-α (IFN-α) induced the transfer of resistance to hepatitis B virus (HBV) from nonpermissive liver nonparenchymal cells (LNPCs) to permissive hepatocytes via exosomes. Exosomes from IFN-α-treated LNPCs were rich in molecules with antiviral activity. Moreover, exosomes from LNPCs were internalized by hepatocytes, which mediated the intercellular transfer of antiviral molecules. Finally, we found that exosomes also contributed to the antiviral response of IFN-α to mouse hepatitis virus A59 and adenovirus in mice. Thus, we propose an antiviral mechanism of IFN-α activity that involves the induction and intercellular transfer of antiviral molecules via exosomes.
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Exosomas/virología , Virus de la Hepatitis B/inmunología , Hepatitis B/inmunología , Interferón-alfa/farmacología , Hígado/virología , Animales , Exosomas/inmunología , Células Hep G2 , Hepatitis B/tratamiento farmacológico , Humanos , Immunoblotting , Hígado/inmunología , Ratones , Transducción de Señal/inmunología , Replicación Viral/inmunologíaRESUMEN
BACKGROUND AND AIMS: Anti-hypertensive agents are one of the most frequently used drugs worldwide. However, no blood pressure-lowering strategy is superior to placebo with respect to survival in diabetic hypertensive patients. Previous findings show that Wnt co-receptors LDL receptor-related proteins 5 and 6 (LRP5/6) can directly bind to several G protein-coupled receptors (GPCRs). Because angiotensin II type 1 receptor (AT1R) is the most important GPCR in regulating hypertension, this study examines the possible mechanistic association between LRP5/6 and their binding protein Dickkopf-1 (DKK1) and activation of the AT1R and further hypothesizes that the LRP5/6-GPCR interaction may affect hypertension and potentiate cardiac impairment in the setting of diabetes. METHODS: The roles of serum DKK1 and DKK1-LRP5/6 signalling in diabetic injuries were investigated in human and diabetic mice. RESULTS: Blood pressure up-regulation positively correlated with serum DKK1 elevations in humans. Notably, LRP5/6 physically and functionally interacted with AT1R. The loss of membrane LRP5/6 caused by injection of a recombinant DKK1 protein or conditional LRP5/6 deletions resulted in AT1R activation and hypertension, as well as ß-arrestin1 activation and cardiac impairment, possibly because of multiple GPCR alterations. Importantly, unlike commonly used anti-hypertensive agents, administration of the anti-DKK1 neutralizing antibody effectively prevented diabetic cardiac impairment in mice. CONCLUSIONS: These findings establish a novel DKK1-LRP5/6-GPCR pathway in inducing diabetic injuries and may resolve the long-standing conundrum as to why elevated blood DKK1 has deleterious effects. Thus, monitoring and therapeutic elimination of blood DKK1 may be a promising strategy to attenuate diabetic injuries.
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Diabetes Mellitus Experimental , Cardiomiopatías Diabéticas , Hipertensión , Receptores de LDL , Animales , Humanos , Ratones , Antihipertensivos , Cardiomiopatías Diabéticas/prevención & control , Hipertensión/prevención & control , Receptores de LDL/antagonistas & inhibidoresRESUMEN
BACKGROUND: The American Heart Association (AHA) has recently introduced the concept of Cardiovascular-Kidney-Metabolic (CKM) syndrome, which is the result of an increasing emphasis on the interplay of metabolic, renal and cardiovascular diseases (CVD). Furthermore, there is substantial evidence of a correlation between the triglyceride glucose-body mass index (TyG-BMI ) and CVD as an assessment of insulin resistance (IR). However, it remains unknown whether this correlation exists in population with CKM syndrome. METHODS: All data for this study were obtained from the China Health and Retirement Longitudinal Study (CHARLS). The exposure was the participants' TyG-BMI at baseline, which was calculated using a combination of triglycerides (TG), fasting blood glucose (FBG) and body mass index (BMI). The primary outcome was CVD, which were determined by the use of a standardised questionnaire during follow-up. To examine the relationship between TyG-BMI and CVD incidence in population with CKM syndrome, both Cox regression analyses and restricted cubic spline (RCS) regression analyses were performed. RESULTS: A total of 7376 participants were included in the final analysis. Of these, 1139, 1515, 1839, and 2883 were in CKM syndrome stages 0, 1, 2, and 3, respectively, at baseline. The gender distribution was 52.62% female, and the mean age was 59.17 ± 9.28 (years). The results of the fully adjusted COX regression analyses indicated that there was a 6.5% increase in the risk of developing CVD for each 10-unit increase in TyG-BMI,95% confidence interval (CI):1.041-1.090. The RCS regression analyses demonstrated a positive linear association between TyG-BMI and the incidence of CVD in the CKM syndrome population (P for overall < 0.001, P for nonlinear = 0.355). CONCLUSIONS: This cohort study demonstrated a positive linear association between TyG-BMI index and increased CVD incidence in a population with CKM syndrome stage 0-3. This finding suggests that enhanced assessment of TyG-BMI index may provide a more convenient and effective tool for individuals at risk for CVD in CKM syndrome stage 0-3.
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Biomarcadores , Glucemia , Índice de Masa Corporal , Enfermedades Cardiovasculares , Síndrome Metabólico , Triglicéridos , Humanos , Síndrome Metabólico/epidemiología , Síndrome Metabólico/diagnóstico , Síndrome Metabólico/sangre , Masculino , Femenino , Persona de Mediana Edad , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/sangre , Estudios Prospectivos , Medición de Riesgo , Triglicéridos/sangre , Incidencia , Anciano , China/epidemiología , Glucemia/metabolismo , Factores de Tiempo , Biomarcadores/sangre , Pronóstico , Enfermedades Renales/epidemiología , Enfermedades Renales/diagnóstico , Enfermedades Renales/sangre , Estudios Longitudinales , Factores de Riesgo de Enfermedad Cardiaca , Resistencia a la Insulina , Factores de RiesgoRESUMEN
BACKGROUND: Numerous studies have confirmed the involvement of extracellular vesicles (EVs) in various physiological processes, including cellular death and tissue damage. Recently, we reported that EVs derived from ischemia-reperfusion heart exacerbate cardiac injury. However, the role of EVs from healthy heart tissue (heart-derived EVs, or cEVs) on myocardial ischemia-reperfusion (MI/R) injury remains unclear. RESULTS: Here, we demonstrated that intramyocardial administration of cEVs significantly enhanced cardiac function and reduced cardiac damage in murine MI/R injury models. cEVs treatment effectively inhibited ferroptosis and maintained mitochondrial homeostasis in cardiomyocytes subjected to ischemia-reperfusion injury. Further results revealed that cEVs can transfer ATP5a1 into cardiomyocytes, thereby suppressing mitochondrial ROS production, alleviating mitochondrial damage, and inhibiting cardiomyocyte ferroptosis. Knockdown of ATP5a1 abolished the protective effects of cEVs. Furthermore, we found that the majority of cEVs are derived from cardiomyocytes, and ATP5a1 in cEVs primarily originates from cardiomyocytes of the healthy murine heart. Moreover, we demonstrated that adipose-derived stem cells (ADSC)-derived EVs with ATP5a1 overexpression showed much better efficacy on the therapy of MI/R injury compared to control ADSC-derived EVs. CONCLUSIONS: These findings emphasized the protective role of cEVs in cardiac injury and highlighted the therapeutic potential of targeting ATP5a1 as an important approach for managing myocardial damage induced by MI/R injury.
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Vesículas Extracelulares , Ratones Endogámicos C57BL , ATPasas de Translocación de Protón Mitocondriales , Daño por Reperfusión Miocárdica , Miocitos Cardíacos , Animales , Masculino , Ratones , Modelos Animales de Enfermedad , Vesículas Extracelulares/metabolismo , Ferroptosis/efectos de los fármacos , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , ATPasas de Translocación de Protón Mitocondriales/metabolismo , Daño por Reperfusión Miocárdica/metabolismo , Miocardio/metabolismo , Miocardio/patología , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismoRESUMEN
BACKGROUND: Allostatic load, the cumulative strain resulting from chronic stress responses, has been linked to disease occurrence and progression, yet research quantifying this relationship is limited. This study aimed to explore the relationship between allostatic load score (ALS) levels and the degree of hepatic steatosis and fibrosis. METHODS: Data from the National Health and Nutrition Examination Survey 2017-2020 were analyzed. The ALS was based on the statistical distribution, assigning one point for each biomarker if it was in the highest risk quartile, and then summing them to generate the ALS score (range, 0-8). The multivariate linear regression was employed to analyze the association between the controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) with ALS. Additionally, multinomial logistic regression was used to investigate the association between ALS and the degree of hepatic steatosis and fibrosis. RESULTS: Participants had a weighted mean age of 52.69 years and 56.14% were female. In the multivariate linear regression analysis, ALS showed a significant positive correlation with CAP (ß = 15.56, 95% CI: 14.50-16.62) and LSM (ß = 0.58, 95% CI: 0.48-0.67). Age, healthy dietary level, and PIR had significant interactions with this positive correlation. In the multinomial logistic regression analysis, ALS exhibited a significant positive correlation with different degrees of hepatic steatosis and fibrosis. Consistency of the results was observed in sensitivity analyses using clinical thresholds of ALS. CONCLUSIONS: Comprehensive clinical assessment targeting load adaptation may enhance the effectiveness of risk assessment in patients with hepatic steatosis and fibrosis.
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Alostasis , Hígado Graso , Cirrosis Hepática , Encuestas Nutricionales , Humanos , Femenino , Masculino , Alostasis/fisiología , Persona de Mediana Edad , Hígado Graso/fisiopatología , Adulto , Anciano , Estudios Transversales , Factores de RiesgoRESUMEN
Anthocyanins are ubiquitous pigments derived from the phenylpropanoid compound conferring red, purple and blue pigmentations to various organs of horticultural crops. The metabolism of flavonoids in the cytoplasm leads to the biosynthesis of anthocyanin, which is then conveyed to the vacuoles for storage by plant glutathione S-transferases (GST). Although GST is important for transporting anthocyanin in plants, its identification and characterization in eggplant (Solanum melongena L.) remains obscure. In this study, a total of 40 GST genes were obtained in the eggplant genome and classified into seven distinct chief groups based on the evolutionary relationship with Arabidopsis thaliana GST genes. The seven subgroups of eggplant GST genes (SmGST) comprise: dehydroascorbate reductase (DHAR), elongation factor 1Bγ (EF1Bγ), Zeta (Z), Theta(T), Phi(F), Tau(U) and tetra-chlorohydroquinone dehalogenase TCHQD. The 40 GST genes were unevenly distributed throughout the 10 eggplant chromosomes and were predominantly located in the cytoplasm. Structural gene analysis showed similarity in exons and introns within a GST subgroup. Six pairs of both tandem and segmental duplications have been identified, making them the primary factors contributing to the evolution of the SmGST. Light-related cis-regulatory elements were dominant, followed by stress-related and hormone-responsive elements. The syntenic analysis of orthologous genes indicated that eggplant, Arabidopsis and tomato (Solanum lycopersicum L.) counterpart genes seemed to be derived from a common ancestry. RNA-seq data analyses showed high expression of 13 SmGST genes with SmGSTF1 being glaringly upregulated on the peel of purple eggplant but showed no or low expression on eggplant varieties with green or white peel. Subsequently, SmGSTF1 had a strong positive correlation with anthocyanin content and with anthocyanin structural genes like SmUFGT (r = 0.9), SmANS (r = 0.85), SmF3H (r = 0.82) and SmCHI2 (r = 0.7). The suppression of SmGSTF1 through virus-induced gene silencing (VIGs) resulted in a decrease in anthocyanin on the infiltrated fruit surface. In a nutshell, results from this study established that SmGSTF1 has the potential of anthocyanin accumulation in eggplant peel and offers viable candidate genes for the improvement of purple eggplant. The comprehensive studies of the SmGST family genes provide the foundation for deciphering molecular investigations into the functional analysis of SmGST genes in eggplant.
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Antocianinas , Regulación de la Expresión Génica de las Plantas , Glutatión Transferasa , Solanum melongena , Antocianinas/metabolismo , Antocianinas/biosíntesis , Arabidopsis/genética , Arabidopsis/metabolismo , Cromosomas de las Plantas/genética , Frutas/genética , Frutas/metabolismo , Genoma de Planta , Glutatión Transferasa/genética , Glutatión Transferasa/metabolismo , Filogenia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Solanum melongena/enzimología , Solanum melongena/genética , Solanum melongena/metabolismoRESUMEN
Background Preoperative assessment of follicular thyroid neoplasms is challenging using the current US risk stratification systems (RSSs) that are applicable to papillary thyroid neoplasms. Purpose To develop a US feature-based RSS for differentiating between follicular thyroid adenoma (FTA) and follicular thyroid carcinoma (FTC) in biopsy-proven follicular neoplasm and compare it with existing RSSs. Materials and Methods This retrospective multicenter study included consecutive adult patients who underwent conventional US and received a final diagnosis of follicular thyroid neoplasm from seven centers between January 2018 and December 2022. US images from a pretraining data set were used to improve readers' understanding of the US characteristics of the FTC and FTA. Univariable and multivariable logistic regression analyses were used to assess the association of qualitative US features with FTC in a training data set. Features with P < .05 were used to construct a prediction model (follicular tumor model, referred to as F model) and RSS for follicular neoplasms using the Thyroid Imaging Reporting and Data System (TI-RADS). Area under the receiver operating characteristic curve (AUC) was compared between follicular TI-RADS (hereafter, F-TI-RADS) and existing RSS (American College of Radiology [ACR] TI-RADS, Korean Society of Thyroid Radiology and Korean Society of Radiology TI-RADS [hereafter, referred to as K-TI-RADS], and Chinese TI-RADS [hereafter, referred to as C-TI-RADS]) in a validation data set. Results The pretraining, training, and validation data sets included 30 (mean age, 47.6 years ± 16.0 [SD]; 16 male patients; FTCs, 30 of 60 [50.0%]), 703 (mean age, 47.9 years ± 14.5; 530 female patients; FTCs, 188 of 703 [26.7%]), and 155 (mean age, 49.9 years ± 13.3 [SD]; 155 female patients; FTCs, 43 of 155 [27.7%]) patients. In the validation data set, the F-TI-RADS showed improved performance for differentiating between FTA and FTC (AUC, 0.81; 95% CI: 0.71, 0.86) compared with ACR TI-RADS (AUC, 0.74; 95% CI: 0.66, 0.80; P = .02), K-TI-RADS (AUC, 0.69; 95% CI: 0.61, 0.76; P = .002), and C-TI-RADS (AUC, 0.68; 95% CI: 0.60, 0.75; P = .002). Conclusion F-TI-RADS outperformed existing RSSs for differentiating between FTC and FTA. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Baumgarten in this issue.
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Neoplasias de la Tiroides , Adulto , Humanos , Femenino , Masculino , Persona de Mediana Edad , Neoplasias de la Tiroides/diagnóstico por imagen , Proyectos de Investigación , Medición de RiesgoRESUMEN
LuxR is a TetR family master quorum sensing (QS) regulator activating or repressing expression of hundreds of genes that control collective behaviors in Vibrios with underlying mechanism unknown. To illuminate how this regulator controls expression of various target genes, we applied ChIP-seq and DNase I-seq technologies. Vibrio alginolyticus LuxR controls expression of â¼280 genes that contain either symmetric palindrome (repDNA) or asymmetric (actDNA) binding motifs with different binding profiles. The median number of LuxR binding sites for activated genes are nearly double for that of repressed genes. Crystal structures of LuxR in complex with the respective repDNA and actDNA motifs revealed a new mode of LuxR DNA binding that involves contacts of its N-terminal extension to the minor groove. The N-terminal contacts mediated by Arginine-9 and Arginine-11 differ when LuxR binds to repDNA vs actDNA, leading to higher binding affinity at repressed targets. Moreover, modification of LuxR binding sites, binding profiles, and N-terminal extension have important consequences on QS-regulated phenotypes. These results facilitate fundamental understanding of the high flexibility of mechanisms of LuxR control of gene activation and repression in Vibrio QS, which may facilitate to design QS inhibiting chemicals that interfere with LuxR regulation to effectively control pathogens.
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Proteínas Bacterianas/química , Regulación Bacteriana de la Expresión Génica , Percepción de Quorum/genética , Proteínas Represoras/química , Transactivadores/química , Activación Transcripcional , Proteínas Bacterianas/metabolismo , Sitios de Unión , ADN/química , Modelos Moleculares , Conformación de Ácido Nucleico , Unión Proteica , Dominios Proteicos , Multimerización de Proteína , Regulón , Vibrio alginolyticus/genéticaRESUMEN
Two-component systems typically consist of a paired histidine kinase and response regulator and couple environmental changes to adaptive responses. The response regulator VbrR from Vibrio parahaemolyticus, a member of the OmpR/PhoB family, regulates virulence and antibiotic resistance genes. The activation mechanism of VbrR remains unclear. Here, we report the crystal structures of full-length VbrR in complex with DNA in the active conformation and the N-terminal receiver domain (RD) and the C-terminal DNA-binding domain (DBD) in both active and inactive conformations. Structural and biochemical analyses suggest that unphosphorylated VbrR adopts mainly as inactive dimers through the DBD at the autoinhibitory state. The RD undergoes a monomer-to-dimer transition upon phosphorylation, which further induces the transition of DBD from an autoinhibitory dimer to an active dimer and enables its binding with target DNA. Our study suggests a new model for phosphorylation-induced activation of response regulators and sheds light on the pathogenesis of V. parahaemolyticus.
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Proteínas Bacterianas , ADN , Fosforilación/fisiología , Proteínas Bacterianas/metabolismo , ADN/metabolismoRESUMEN
OBJECTIVE: It is unclear if prehospital intubation improves survival in patients with traumatic brain injury. We performed a systematic review and meta-analysis to assess the impact of prehospital intubation on mortality rates of traumatic brain injury. METHODS: PubMed, CENTRAL, Web of Science, and Embase databases were searched without any language restriction up to 20 June 2022 for all types of comparative studies reporting survival of traumatic brain injury patients based on prehospital intubation. RESULTS: In total, 18 studies with 41,185 patients were eligible for inclusion. Meta-analysis showed that traumatic brain injury patients receiving prehospital intubation had higher odds of mortality as compared to those not receiving prehospital intubation. Meta-analysis of adjusted data also indicated that prehospital intubation was associated with increased odds of mortality in traumatic brain injury patients. The results did not change on sensitivity analysis. Subgroup analysis based on study type, the severity of traumatic brain injury, inclusion of isolated traumatic brain injury, emergency department intubation in the control group, and prehospital intubation group sample size demonstrated variable results. CONCLUSION: Heterogeneous data from mostly observational studies demonstrates higher mortality rates among traumatic brain injury patients receiving prehospital intubation. The efficacy of prehospital intubation is difficult to judge without taking into account multiple confounding factors.
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Lesiones Traumáticas del Encéfalo , Servicios Médicos de Urgencia , Humanos , Intubación Intratraqueal/métodos , Lesiones Traumáticas del Encéfalo/terapia , Servicio de Urgencia en HospitalRESUMEN
A meta-analysis was performed to comprehensively assess the effects of video-assisted thoracoscopy on surgical site wound infection and wound pain in patients with lung cancer. Studies on video-assisted thoracoscopy for lung cancer were collected from PubMed, EMBASE, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, and Wanfang database, from inception to January 2023. Two researchers independently screened the literature, extracted the data, and evaluated the quality of the included studies according to the inclusion and exclusion criteria. Meta-analysis was performed using RevMan 5.4 software. Thirty-one articles with a total of 3608 patients were included, with 1809 in the video-assisted thoracoscopy group and 1799 in the control group. Compared with the control group, video-assisted thoracoscopy significantly reduced surgical site wound infection (odds ratio: 0.22, 95% confidence interval [CI]: 0.14-0.33, P < .001) and surgical site wound pain at postoperative day 1 (standardised mean difference [SMD]: -0.90, 95% CI: -1.17 to -0.64, P < .001) and postoperative day 3 (SMD: -1.59, 95% CI: -2.25 to -0.92, P < .001). Thus, these results showed that video-assisted thoracoscopy may have beneficial outcomes by reducing surgical site wound infection and pain. However, owing to the large variation in sample sizes and some methodological shortcomings, further validation is needed in future studies with higher quality and larger sample sizes.
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Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/cirugía , Infección de la Herida Quirúrgica/etiología , Dolor , Toracoscopía , ChinaRESUMEN
One of the key challenges of improving clinical outcomes of antibody drug conjugates (ADCs) is overcoming cancer resistance to the antibody and/or drug components of ADCs, and hence the need for ADC platforms with high combinatory flexibility. Here, we introduce the use of self-assembled left-handed DNA (L-DNA) oligonucleotides to link combinatory single-domain antibodies and toxin payloads for tunable and adaptive delivery of ADCs. We demonstrate that the method allows convenient construction of a library of ADCs with multi-specific targeting, multi-specific payloads, and exact drug-antibody ratio. The newly constructed ADCs with L-DNA scaffold showed favorable properties of in vitro cell cytotoxicity and in vivo suppression and eradication of solid tumors. Collectively, our data suggest that the L-DNA based modular ADC (MADC) platform is a viable option for generating therapeutic ADCs and for potentially expanding ADC therapeutic window via multi-specificity.
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Antineoplásicos , Inmunoconjugados , Neoplasias , Humanos , Anticuerpos , ADN , Antineoplásicos/farmacologíaRESUMEN
OBJECTIVE: Using a common DR chest radiography system to realize a long bone stitching technology. METHODS: Introduce the role of long bone stitching technology in medical diagnosis and treatment, and the principle of long bone stitching technology to make a long bone stitching radiographic device, and combine with the chest radiography system to take the long bone stitching image experiment. RESULTS: The hospitals of class â ¡ (or more lower levels) can realize the long bone stitching technology using a common DR chest radiography system. CONCLUSIONS: Using this technology can save the hospital costs, reduce the burden on patients, achieve good social and economic benefits.
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Hospitales , Intensificación de Imagen Radiográfica , Humanos , Radiografía , TecnologíaRESUMEN
Extracellular vesicles (EVs) play important roles in cardiovascular diseases by delivering their RNA cargos. However, the features and possible role of the lncRNAs and mRNAs in cardiac EVs during ischemia-reperfusion (IR) remain unclear. Therefore, we performed RNA sequencing analysis to profile the features of lncRNAs and mRNAs and predicted their potential functions. Here, we demonstrated that the severity of IR injury was significantly correlated with cardiac EV production. RNA sequencing identified 73 significantly differentially expressed (DE) lncRNAs (39 upregulated and 34 downregulated) and 720 DE-mRNAs (317 upregulated and 403 downregulated). Gene Ontology (GO) and pathway analysis were performed to predict the potential functions of the DE-lncRNAs and mRNAs. The lncRNA-miRNA-mRNA ceRNA network showed the possible functions of DE-lncRNAs with DE-mRNAs which are enriched in the pathways of T cell receptor signalling pathway and cell adhesion molecules. Moreover, the expressions of ENSMUST00000146010 and ENSMUST00000180630 were negatively correlated with the severity of IR injury. A significant positive correlation was revealed between TCONS_00010866 expression and the severity of the cardiac injury. These findings revealed the lncRNA and mRNA profiles in the heart derived EVs and provided potential targets and pathways involved in cardiac IR injury.
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Vesículas Extracelulares , MicroARNs , ARN Largo no Codificante , Daño por Reperfusión , Ratones , Animales , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Redes Reguladoras de Genes , Vesículas Extracelulares/genética , Vesículas Extracelulares/metabolismo , MicroARNs/genética , Daño por Reperfusión/genética , Perfilación de la Expresión GénicaRESUMEN
Accumulating evidence suggests that supplementation of n-3 PUFA was associated with reduction in risk of major cardiovascular events. This meta-analysis was to systematically evaluate whether daily supplementation and accumulated intake of n-3 PUFA are associated with improved left ventricular (LV) remodelling in patients with chronic heart failure (CHF). Articles were obtained from Pubmed, Clinical key and Web of Science from inception to January 1 in 2021, and a total of twelve trials involving 2162 participants were eligible for inclusion. The sources of study heterogeneity were explained by I2 statistic and subgroup analysis. Compared with placebo groups, n-3 PUFA supplementation improved LV ejection fraction (LVEF) (eleven trials, 2112 participants, weighted mean difference (WMD) = 2·52, 95 % CI 1·25, 3·80, I2 = 87·8 %) and decreased LV end systolic volume (five studies, 905 participants, WMD = -3·22, 95 % CI 3·67, -2·77, I2 = 0·0 %) using the continuous variables analysis. Notably, the high accumulated n-3 PUFA dosage groups (≥ 600 g) presented a prominent improvement in LVEF, while the low and middle accumulated dosage (≤ 300 and 300-600 g) showed no effects on LVEF. In addition, n-3 PUFA supplementation decreased the levels of pro-inflammatory mediators including TNF-α, IL-6 (IL-6) and hypersensitive c-reactive protein. Therefore, the present meta-analysis demonstrated that n-3 PUFA consumption was associated with a substantial improvement of LV function and remodelling in patients subjected to CHF. The accumulated dosage of n-3 PUFA intake is vital for its cardiac protective role.
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The cpxR gene, encoding a new cytoplasmic response regulator, which effects virulence, biofilm formation, chemotaxis, resistance to antimicrobials, and controls soft rot, was amplified by the polymerase chain reaction, cloned into the prokaryotic expression vector pET-15b, and expressed through the induction of isopropyl-ß-d-thiogalactoside in Escherichia coli BL21 (DE3). Then, highly purified and stable CpxR protein was produced by nickel affinity chromatography and fast protein liquid chromatography, digested by thrombin and identified by Western blotting. Furthermore, the structure of the CpxR protein was estimated by circular dichroism spectroscopy and SWISS-MODEL. The CpxR protein was a functional part in signal transduction and bacterial resistance for Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. The resear ch of the protein stability indicated the CpxR protein had excellent thermal stability and was suitable for crystallization. Then the small crystals of CpxR protein were found in the crystallizing tank. The latest 34 cpxR sequences from the public database were selected and analyzed by molecular clustering and multisequence alignment. These cpxR sequences were roughly divided into four categories. These results laid an important foundation for the further structural study of the CpxR protein.
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Escherichia coli , Pectobacterium carotovorum , Proteínas Bacterianas/metabolismo , Clonación Molecular , Escherichia coli/genética , Escherichia coli/metabolismo , Pectobacterium carotovorum/genética , Reacción en Cadena de la PolimerasaRESUMEN
OBJECTIVES: Outcomes of ultrasound-guided saline enema include successful treatment, unsuccessful treatment, or recurrence. This study aimed to investigate the value of ultrasonic parameters of the ileocecal region during hydrostatic reduction to predict enema outcomes. METHODS: Ultrasound images of patients diagnosed with ileocolic intussusception and treated with ultrasound-guided saline enema at two different institutions between January 2019 and April 2021 were retrospectively analyzed to assess ileocecal-valve diameter (ICVD), intussusceptum thickness (IT), and the ratio of IT to ICVD (I/I). Logistic regression analysis was used to explore correlations between ICVD, IT, I/I, and patient characteristics (sex, age, symptom duration, and enema outcome). RESULTS: Of 291 patients with ileocolic intussusception (207 boys; mean ICVD, 8.6 [SD: 0.1] mm; mean IT, 26 [SD: 0.2] mm; mean I/I, 3.0 [SD: 0.01]), 268 had first successful reduction; 23, first failed reduction; 7, final failed reduction; and 41, early recurrence. Significant risk factors for failed reduction included symptom duration >24 hours (odds ratio [OR] = 10, P = .012), ICVD ≤ 8.5 mm (OR = 8, P = .01), and I/I > 3.25 (OR = 16, P < .001). Significant risk factors for early recurrence post-enema included age >1 year (OR = 10, P = .028), ICVD > 8.5 mm (OR = 4, P = .003), and I/I ≤ 2.95 (OR = 6, P < .001). CONCLUSIONS: ICVD and IT measured during ultrasound-guided hydrostatic reduction can predict enema outcomes. The mismatch between IT and ICVD is the primary cause of poor outcomes.
Asunto(s)
Enfermedades del Íleon , Intususcepción , Masculino , Niño , Humanos , Lactante , Intususcepción/diagnóstico por imagen , Intususcepción/terapia , Estudios Retrospectivos , Estudios de Casos y Controles , Resultado del Tratamiento , Enema/métodos , Solución Salina , Ultrasonografía Intervencional , Enfermedades del Íleon/terapiaRESUMEN
This study aims to evaluate the feasibility and cardio-protective effects of biocompatible silicon-built restraint device (ASD) in the rat's heart failure (HF) model. The performance and compliance characteristics of the ASD device were assessed in vitro by adopting a pneumatic drive and ball burst test. Sprague-Dawley (SD) rats were divided into four groups (n = 6); control, HF, HF + CSD, and HF + ASD groups, respectively. Heart failure was developed by left anterior descending (LAD) coronary artery ligation in all groups except the control group. The ASD and CSD devices were implanted in the heart of HF + ASD and HF + CSD groups, respectively. The ASD's functional and expansion ability was found to be safe and suitable for attenuating ventricular remodeling. ASD-treated rats showed normal heart rhythm, demonstrated by smooth -ST and asymmetrical T-wave. At the same time, hemodynamic parameters of the HF + ASD group improved systolic and diastolic functions, reducing ventricular wall stress, which indicated reverse remodeling. The BNP values were reduced in the HF + ASD group, which confirmed ASD feasibility and reversed remodeling at a molecular level. Furthermore, the HF + ASD group with no fibrosis suggests that ASD has significant curative effects on the heart muscles. In conclusion, ASD was found to be a promising restraint therapy than the previously standard restraint therapies. Stepwise ASD fabrication process (a) 3D computer model of ASD was generated by using Rhinoceros 5.0 software (b) 3D blue wax model of ASD (c) Silicon was prepared by mixing the solutions (as per manufacturer instruction) (d) Blue wax model of ASD was immersed into liquid Silicon (e) ASD model was put into the oven for 3 hours at 50 °C. (f) Blue wax started melting from the ASD model (g) ASD model was built from pure silicon (h) Two access lines were linked to the ASD device, which was connected with an implantable catheter (Port-a-cath), scale bar 100 µm. (Nikon Ldx 2.0).
Asunto(s)
Insuficiencia Cardíaca , Remodelación Ventricular , Animales , Insuficiencia Cardíaca/terapia , Hemodinámica , Ratas , Ratas Sprague-Dawley , SilicioRESUMEN
The color of fruit peel is an economically important character of eggplant, and black-purple eggplant has received much attention for being rich in anthocyanin. However, the reason why different fruit peel colors form in eggplant is not well understood. In the present study, an integrative analysis of the metabolome and transcriptome profiles was performed in five eggplant varieties with different fruit colors. A total of 260 flavonoids were identified, and most of them showed significantly higher abundance in black-purple varieties than in other varieties. The transcriptome analysis indicated the activation of early phenylpropanoid biosynthesis genes (SmPAL, SmC4H, and Sm4CL) was more responsible for anthocyanin accumulation, while SmF3'5'H was the key factor for the formation of a purple color. Furthermore, two transcription factors, SmGL2 and SmGATA26, were identified as new hub genes associated with anthocyanin accumulation. The silencing of SmGL2 and SmGATA26 reduced anthocyanin accumulation in eggplant fruit peels, suggesting the possible involvement of SmGL2 and SmGATA26 in regulating anthocyanin biosynthesis. In addition, the pathway of plant hormone signal transduction was significantly enriched, indicating that phytohormones may cooperatively interact to modulate flavonoid biosynthesis. This study provides comprehensive information of flavonoid metabolites and new insights into the regulatory network of fruit coloration, which might be useful for the molecular breeding of eggplant.