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Mastitis caused by antibiotic-resistant strains of Staphylococcus aureus is a significant concern in the livestock industry due to the economic losses it incurs. Regulating immunometabolism has emerged as a promising approach for preventing bacterial inflammation. To investigate the possibility of alleviating inflammation caused by S aureus infection by regulating host glycolysis, we subjected the murine mammary epithelial cell line (EpH4-Ev) to S aureus challenge. Our study revealed that S aureus can colonize EpH4-Ev cells and promote inflammation through hypoxic inducible factor 1α (HIF1α)-driven glycolysis. Notably, the activation of HIF1α was found to be dependent on the production of reactive oxygen species (ROS). By inhibiting PFKFB3, a key regulator in the host glycolytic pathway, we successfully modulated HIF1α-triggered metabolic reprogramming by reducing ROS production in S aureus-induced mastitis. Our findings suggest that there is a high potential for the development of novel anti-inflammatory therapies that safely inhibit the glycolytic rate-limiting enzyme PFKFB3.
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Mastitis , Staphylococcus aureus , Femenino , Animales , Ratones , Humanos , Especies Reactivas de Oxígeno/metabolismo , Staphylococcus aureus/metabolismo , Células Epiteliales/microbiología , Inflamación , Glucólisis , Proliferación Celular , Fosfofructoquinasa-2/metabolismoRESUMEN
Staphylococcus aureus (S. aureus) persists within mammary epithelial cells for an extended duration, exploiting the host metabolic resources to facilitate replication. This study revealed a mechanism by which intracellular S. aureus reprograms host metabolism, with PFKFB3 playing a crucial role in this process. Mechanistically, S. aureus induced mitochondrial damage, leading to increased levels of mitochondrial reactive oxygen species (mROS) and dysfunction in electron transport chain (ETC). Moreover, S. aureus shifted the balance of mitochondrial dynamics from fusion to fission, subsequently activating PINK1-PRKN-dependent mitophagy, causing loss of the sirtuin 3 (SIRT3) to stabilize hypoxic inducible factor 1α (HIF1α), and shifting the host metabolism toward enhanced glycolysis. The inhibition of PFKFB3 reversed the mitochondrial damage and degradation of SIRT3 induced by S. aureus. Overall, our findings elucidate the mechanism by which S. aureus reprograms host metabolism and offer insights into the treatment of S. aureus infection.
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Adjuvants play a critical role in the induction of effective immune responses by vaccines. Here, a self-assembling nanovaccine platform that integrates adjuvant functions into the delivery vehicle is prepared. Cationic Lentinan (CLNT) is mixed with ovalbumin (OVA) to obtain a self-assembling nanovaccine (CLNTO nanovaccine), which induces the uptake and maturation of bone marrow dendritic cells (BMDCs) via the toll-like receptors 2/4 (TLR2/4) to produce effective antigen cross-presentation. CLNTO nanovaccines target lymph nodes (LNs) and induce a robust OVA-specific immune response via TLR and tumor necrosis factor (TNF) signaling pathways, retinoic acid-inducible gene I (RIG-I) receptor, and cytokine-cytokine receptor interactions. In addition, CLNTO nanovaccines are found that promote the activation of follicular helper T (Tfh) cells and induce the differentiation of germinal center (GC) B cells into memory B cells and plasma cells, thereby enhancing the immune response. Vaccination with CLNTO nanovaccine significantly inhibits the growth of ovalbumin (OVA)-expressing B16 melanoma cell (B16-OVA) tumors, indicating its great potential for cancer immunotherapy. Therefore, this study presents a simple, safe, and effective self-assembling nanovaccine that induces helper T cell 1 (Th1) and helper T cell (Th2) immune responses, making it an effective vaccine delivery system.
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BACKGROUND: Poststroke cognitive impairment (PSCI) is highly prevalent in stroke survivors and correlated with unfavorable clinical outcomes. This study aimed to identify the neural substrate of PSCI using atlas-based disconnectome analysis and assess the value of disconnection score, a baseline measure for stroke-induced structural disconnection, in PSCI prediction. METHODS: A multicenter prospective cohort of 676 first-ever patients with acute ischemic stroke was enrolled from 3 independent hospitals in China. Sociodemographic, clinical, and neuroimaging data were collected at acute stage of stroke. Cognitive assessment was performed at 3 months after stroke. Voxel-wise and tract-wise disconnectome analysis were performed to uncover the strategic structural disconnection pattern for global PSCI. Disconnection score was calculated for each participant in leave-one-dataset-out cross-validation. Multivariable logistic regression was performed for the association between disconnection score and PSCI. Prediction models with and without disconnection score were developed, cross-validated, and compared in terms of discrimination and goodness-of-fit. RESULTS: Compared with lesions of non-PSCI, those of PSCI were more likely to have fiber connections with left prefrontal cortex and left deep structures (thalamus and basal ganglia). Disconnection score could predict the risk and severity of PSCI during cross-validation, and was independently associated with PSCI after controlling for all baseline covariates (odds ratio, 1.38 [95% CI, 1.17-1.64]; P<0.001). Incorporating disconnection score into a reference model with 6 known predictors resulted in significant improvement in both discrimination and goodness-of-fit throughout cross-validation. CONCLUSIONS: A strategic structural disconnection pattern centered on left prefrontal cortex, thalamus, and basal ganglia is identified for global PSCI using indirect disconnectome analysis. The baseline disconnection score is independently predictive of PSCI and has significant incremental value to preexisting sociodemographic, clinical, and neuroimaging predictors. REGISTRATION: URL: http://www.chictr.org.cn/enIndex.aspx; Unique identifier: ChiCTR-ROC-17013993.
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Disfunción Cognitiva , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Accidente Cerebrovascular Isquémico/complicaciones , Estudios Prospectivos , Accidente Cerebrovascular/complicaciones , Disfunción Cognitiva/psicología , Modelos LogísticosRESUMEN
Macrophages play a pivotal role in the inflammatory response to the zoonotic pathogen E. coli, responsible for causing enteric infections. While considerable research has been conducted to comprehend the pathogenesis of this disease, scant attention devoted to host-derived H2S. Herein, we reported that E. coli infection enhanced the expression of CSE in macrophages, accompanied by a significantly increased inflammatory response. This process may be mediated by the involvement of excessive autophagy. Inhibition of AMPK or autophagy with pharmacological inhibitors could alleviate the inflammation. Additionally, cell model showed that the mRNA expression of classic inflammatory factors (Il-1ß, Il-6), macrophage polarization markers (iNOS, Arg1) and ROS production was significantly down-regulated after employing CSE specific inhibitor PAG. And PAG is capable of inhibiting excessive autophagy through the LKB1-AMPK-ULK1 axis. Interestingly, exogenous H2S could suppress inflammation response. Our study emphasizes the importance of CSE in regulating the macrophage-mediated response to E. coli. Increased CSE in macrophages leads to excessive inflammation, which should be considered a new target for drug development to treat intestinal infection.
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Infecciones por Escherichia coli , Escherichia coli , Animales , Proteínas Quinasas Activadas por AMP , Infecciones por Escherichia coli/tratamiento farmacológico , Infecciones por Escherichia coli/veterinaria , Transducción de Señal , Inflamación/veterinariaRESUMEN
SARS-CoV-2, the pathogen of COVID-19, has introduced massive confirmed cases and millions of deaths worldwide, which poses a serious public health threat. For the early diagnosis of COVID-19, we have constructed an electrochemical biosensor-combined magnetic separation system with copper nanoflower-triggered cascade signal amplification strategy. In the proposed system, magnetic beads were utilized to fabricate the recognition element for capturing the conserved sequence of SARS-CoV-2. As the copper ions source, oligonucleotides modified copper nanoflowers with special layered structure provide numerous catalysts for click chemistry reaction. When target sequence RdRP_SARSr-P2 appears, copper nanoflowers will be bound with magnetic beads, thus prompting the Cu(I)-catalyzed azide-alkyne cycloaddition reaction through the connection of the SARS-CoV-2 conserved sequence. Then, a large number of signal molecules FMMA can be grafted onto the modified electrode surface by electrochemically mediated atom-transfer radical polymerization to amplify the signal for the quantitative analysis of SARS-CoV-2. Under optimal conditions, a linear range from 0.1 to 103 nM with a detection limit of 33.83 pM is obtained. It provides a powerful tool for the diagnosis of COVID-19, which further benefits the early monitoring of other explosive infectious diseases effectively, thus guaranteeing public health safety.
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Técnicas Biosensibles , COVID-19 , Humanos , ADN/química , Polímeros/química , Cobre/química , SARS-CoV-2 , COVID-19/diagnóstico , Técnicas Electroquímicas , Límite de Detección , Química ClicRESUMEN
BACKGROUND: Post-stroke depression (PSD) can be conceptualized as a complex network where PSD symptoms (PSDS) interact with each other. The neural mechanism of PSD and interactions among PSDS remain to be elucidated. This study aimed to investigate the neuroanatomical substrates of, as well as the interactions between, individual PSDS to better understand the pathogenesis of early-onset PSD. METHODS: A total of 861 first-ever stroke patients admitted within 7 days poststroke were consecutively recruited from three independent hospitals in China. Sociodemographic, clinical and neuroimaging data were collected upon admission. PSDS assessment with Hamilton Depression Rating Scale was performed at 2 weeks after stroke. Thirteen PSDS were included to develop a psychopathological network in which central symptoms (i.e. symptoms most strongly correlated with other PSDS) were identified. Voxel-based lesion-symptom mapping (VLSM) was performed to uncover the lesion locations associated with overall PSDS severity and severities of individual PSDS, in order to test the hypothesis that strategic lesion locations for central symptoms could significantly contribute to higher overall PSDS severity. RESULTS: Depressed mood, Psychiatric anxiety and Loss of interest in work and activities were identified as central PSDS at the early stage of stroke in our relatively stable PSDS network. Lesions in bilateral (especially the right) basal ganglia and capsular regions were found significantly associated with higher overall PSDS severity. Most of the above regions were also correlated with higher severities of 3 central PSDS. The other 10 PSDS could not be mapped to any certain brain region. CONCLUSIONS: There are stable interactions among early-onset PSDS with Depressed mood, Psychiatric anxiety and Loss of interest as central symptoms. The strategic lesion locations for central symptoms may indirectly induce other PSDS via the symptom network, resulting in higher overall PSDS severity. TRIAL REGISTRATION: URL: http://www.chictr.org.cn/enIndex.aspx ; Unique identifier: ChiCTR-ROC-17013993.
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Trastornos Mentales , Accidente Cerebrovascular , Humanos , Depresión/psicología , Accidente Cerebrovascular/complicaciones , Encéfalo/patología , Ansiedad , Trastornos Mentales/complicacionesRESUMEN
Alzheimer's disease (AD), an age-dependent neurodegenerative disorder, is the most prevalent neurodegenerative disease worldwide. The primary pathological hallmarks of AD are the deposition of ß-amyloid plaques and neurofibrillary tangles. Autophagy, a pathway of clearing damaged organelles, macromolecular aggregates, and long-lived proteins via lysosomal degradation, has emerged as critical for proteostasis in the central nervous system (CNS). Studies have demonstrated that defective autophagy is strongly implicated in AD pathogenesis. Transcription factor EB (TFEB), a master transcriptional regulator of autophagy, enhances the expression of related genes that control autophagosome formation, lysosome function, and autophagic flux. The study of TFEB has greatly increased over the last decade, and the dysfunction of TFEB has been reported to be strongly associated with the pathogenesis of many neurodegenerative disorders, including AD. Here, we delineate the basic understanding of TFEB dysregulation involved in AD pathogenesis, highlighting the existing work that has been conducted on TFEB-mediated autophagy in neurons and other nonneuronal cells in the CNS. Additionally, we summarize the small molecule compounds that target TFEB-regulated autophagy involved in AD therapy. Our review may yield new insights into therapeutic approaches by targeting TFEB and provide a broadly applicable basis for the clinical treatment of AD.
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Enfermedad de Alzheimer , Enfermedades Neurodegenerativas , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/genética , Péptidos beta-Amiloides/metabolismo , Autofagia/fisiología , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/genética , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/metabolismo , Humanos , Lisosomas/metabolismo , Enfermedades Neurodegenerativas/metabolismo , Placa Amiloide/metabolismoRESUMEN
BACKGROUND: Post-stroke depression (PSD) is the most common psychological consequence of stroke. Increased inflammatory markers resulting from ischemic stroke may played an important role in the pathogenesis of depressive symptomology. The present study was conducted to further elucidate the relationship between stroke severity, systemic low-grade inflammation and chronic phase post-stroke depressive symptomology (CP-PSDS). METHODS: A total of 897â¯stroke patients were consecutively recruited in this multicenter prospective cohort study and followed up for 1â¯year. The analytical sample consisted of 436 patients with ischemic stroke (23.4% female, median ageâ¯=â¯57â¯years) from this cohort. Serum concentrations of inflammatory markers were measured in all 436 patients with ischemic stroke, from fasting morning venous blood samples on admission. Stroke severity was evaluated using the National Institutes of Health Stroke Scale (NIHSS) on admission and post-stroke depressive symptomology (PSDS) was evaluated by 17-item Hamilton Rating Scale for Depression (HRSD). RESULTS: In the fully adjusted models, we observed that 1) NIHSS (Model 2: ßâ¯=â¯0.200, 95%CI, 0.057â¯â¼â¯0.332), fibrinogen (Model 2: ßâ¯=â¯0.828, 95%CI, 0.269â¯â¼â¯1.435), white blood cell counts (WBC, model 2: ßâ¯=â¯0.354, 95%CI, 0.122â¯â¼â¯0.577) and neutrophil counts (Model 2: ßâ¯=â¯0.401, 95%CI, 0.126â¯â¼â¯0.655) can independently predict the CP-PSDS after ischemic stroke onset; 2) fibrinogen (Indirect effectâ¯=â¯0.027, 95%CI, 0.007â¯â¼â¯0.063, 13.4% mediated), WBC (Indirect effectâ¯=â¯0.024, 95%CI, 0.005â¯â¼â¯0.058, 11.8% mediated) and neutrophil counts (Indirect effectâ¯=â¯0.030, 95%CI, 0.006â¯â¼â¯0.069, 14.8% mediated) could partially mediate the association between stroke severity and CP-PSDS, and 3) stroke severity might cause CP-PSDS partly through the chain-mediating role of both fibrinogen and neutrophil counts (chain mediated effectâ¯=â¯0.003, 95%CI, 0.000â¯â¼â¯0.011, pâ¯=â¯0.025, 1.6% mediated). CONCLUSIONS: Findings revealed that fibrinogen, WBC and neutrophil counts may be independent predictors of CP-PSDS and partial mediators of the relationship between stroke severity and CP-PSDS among patients with ischemic stroke. In addition, the chain mediating effect of fibrinogen and neutrophil counts might play an important role in the occurrence of CP-PSDS. However, no inflammatory markers were associated with CP-PSDS in females.
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Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Isquemia Encefálica/complicaciones , Depresión/epidemiología , Femenino , Fibrinógeno , Humanos , Inflamación , Masculino , Persona de Mediana Edad , Neutrófilos , Estudios ProspectivosRESUMEN
Foamy macrophages containing prominent cytoplasmic lipid droplets (LDs) are found in a variety of infectious diseases. However, their role in Streptococcus uberis-induced mastitis is unknown. Herein, we report that S. uberis infection enhances the fatty acid synthesis pathway in macrophages, resulting in a sharp increase in LD levels, accompanied by a significantly enhanced inflammatory response. This process is mediated by the involvement of fatty acid binding protein 4 (FABP4), a subtype of the fatty acid-binding protein family that plays critical roles in metabolism and inflammation. In addition, FABP4 siRNA inhibitor cell models showed that the deposition of LDs decreased, and the mRNA expression of Tnf, Il1b and Il6 was significantly downregulated after gene silencing. As a result, the bacterial load in macrophages increased. Taken together, these data demonstrate that macrophage LD formation is a host-driven component of the immune response to S. uberis. FABP4 contributes to promoting inflammation via LDs, which should be considered a new target for drug development to treat infections.
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Enfermedades de los Bovinos , Mastitis Bovina , Infecciones Estreptocócicas , Femenino , Animales , Bovinos , Gotas Lipídicas/metabolismo , Macrófagos/microbiología , Proteínas de Unión a Ácidos Grasos/genética , Proteínas de Unión a Ácidos Grasos/metabolismo , Inflamación/metabolismo , Inflamación/veterinaria , Infecciones Estreptocócicas/veterinaria , Mastitis Bovina/microbiología , Enfermedades de los Bovinos/metabolismoRESUMEN
Streptococcus uberis is a common cause of mastitis. The pathogenicity among different strains of S. uberis and the resultant host immune responses remain to be elucidated. Herein, we document immune responses among three strains of S. uberis, and preliminary explore whether and how intestinal immunity plays a role in host anti-infection processes. Mice have been proved to be effective experimental animals for bovine mastitis, so utilizing a mouse intramammary infection model, we assay immune responses and gut flora changes of three S. uberis strains by histopathologic examination, RT-PCR, Western blot, and 16s ribosomal DNA sequencing. We find that the immune responses among the three sequence-type (ST) S. uberis strains may be linked to the hasA/B and lbp virulence genes, and the beta diversity of the intestine may be independent of the ST of S. uberis. Twenty phyla and 30 genera of intestinal flora were identified, with Verrucomicrobia and Akkermansia being the most prominent phylum and genus, respectively. These bacteria have strong anti-inflammatory and protective effects against S. uberis challenge. These data provide a foundation for further studies to elucidate gut flora function and exploration of therapeutic targets for mastitis.
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Microbioma Gastrointestinal , Mastitis Bovina , Infecciones Estreptocócicas , Animales , Bovinos , Femenino , Humanos , Inmunidad , Ratones , Infecciones Estreptocócicas/microbiología , StreptococcusRESUMEN
BACKGROUND: Post-stroke depression (PSD) is one of the most common neuropsychiatric complications after stroke. Studies on the underlying mechanisms and biological markers of sex differences in PSD are of great significance, but there are still few such studies. Therefore, the main objective of this study was to investigate the association of biomarkers with PSD at 3 months after minor stroke in men and women. METHODS: This was a prospective multicenter cohort study that enrolled 530 patients with minor stroke (males, 415; females, 115). Demographic information and blood samples of patients were collected within 24 h of admission, and followed up at 3 months after stroke onset. PSD was defined as a depressive disorder due to another medical condition with depressive features, major depressive-like episode, or mixed-mood features according to the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-V). Univariate analysis was performed using the chi-square test, Mann-Whitney U test, or t-test. Partial least-squares discriminant analysis (PLS-DA) was used to distinguish between patients with and without PSD. Factors with variable importance for projection (VIP) > 1.0 were classified as the most important factors in the model segregation. RESULTS: The PLS-DA model mainly included component 1 and component 2 for males and females. For males, the model could explain 13% and 16.9% of the variables, respectively, and 29.9% of the variables in total; the most meaningful predictors were exercise habit and fibrinogen level. For females, the model could explain 15.7% and 10.5% of the variables, respectively, and 26.2% of the variables in total; the most meaningful predictors in the model were brain-derived neurotrophic factor (BDNF), magnesium and free T3. Fibrinogen was positively correlated with the Hamilton Depression Scale-17 items (HAMD-17) score. BDNF, magnesium, and free T3 levels were negatively correlated with the HAMD-17 score. CONCLUSIONS: This was a prospective cohort study. The most important markers found to be affecting PSD at 3 months were fibrinogen in males, and free T3, magnesium, and BDNF in females. TRIAL REGISTRATION: ChiCTR-ROC-17013993 .
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Trastorno Depresivo Mayor , Accidente Cerebrovascular , Biomarcadores , Factor Neurotrófico Derivado del Encéfalo , Estudios de Cohortes , Depresión/diagnóstico , Depresión/etiología , Trastorno Depresivo Mayor/complicaciones , Trastorno Depresivo Mayor/etiología , Femenino , Fibrinógeno , Humanos , Magnesio , Masculino , Estudios Prospectivos , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/psicologíaRESUMEN
BACKGROUND: Post-stroke depression (PSD) is one of the most common neuropsychiatric complications after stroke. The occurrence, development and prognosis of PSD have long been different between males and females. The main purpose of this study was to explore the influencing factors of PSD at 3 months in males and females, and construct random forest (RF) models to rank the influencing factors. METHODS: This is a prospective multicenter cohort study (Registration number: ChiCTR-ROC-17013993). Stroke patients hospitalized in the department of Neurology of three hospitals in Wuhan were enrolled from May 2018 to August 2019. Scale assessments were performed 24 hours after admission and 3 months after stroke onset. Binary logistic regression analysis was used for univariate and multivariate (stepwise backward method) analysis, when p was less than 0.05, the difference between groups was considered statistically significant. Lastly, the RF models were constructed according to the results of multivariate regression analysis. RESULTS: This study found that several baseline variables were associated with PSD at 3 months in males and females. RF model ranked them as stroke severity (OR [odds ratio] =1.17, p < 0.001, 95%CI [confidence interval]:1.11-1.24), neuroticism dimension (OR = 1.06, p = 0.002, 95%CI:1.02-1.10), physical exercise (OR = 0.62, p = 0.007, 95%CI:0.44-0.88), sleeping time < 5 h (OR = 1.91, p = 0.006, 95% CI:1.20-3.04) and atrial fibrillation (OR = 4.18, p = 0.012, 95%CI:1.38-12.68) in males. In females, RF model ranked them as psychological resilience (OR = 0.98, p = 0.015, 95%CI:0.96-1.00), ability of daily living (OR = 0.98, p = 0.001, 95%CI:0.97-0.99), neuroticism dimension (OR = 1.11, p = 0.002, 95%CI:1.04-1.18) and subjective support (OR = 1.11, p < 0.001, 95%CI:1.05-1.78). CONCLUSION: The study found influencing factors of PSD at 3 months were different in males and females, and construct RF models to rank them according to their importance. This suggests that clinicians should focus their interventions on sex-specific influencing factors in order to improve the prognosis of PSD patients. TRIAL REGISTRATION: ChiCTR-ROC-17013993.
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Depresión , Accidente Cerebrovascular , Masculino , Humanos , Femenino , Depresión/etiología , Depresión/epidemiología , Estudios de Cohortes , Estudios Prospectivos , Bosques Aleatorios , Factores de Riesgo , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/epidemiologíaRESUMEN
Mammary gland-derived Escherichia coli is an important pathogen causing dairy cow mastitis. Mammary gland mucosal immunity against infectious E. coli mainly depends on recognition of pathogen-associated molecular patterns by innate receptors. Stimulator of interferon (IFN) gene (STING) has recently been the dominant mediator in reacting to bacterial intrusion and preventing inflammatory disorders. In this study, we first proved that the diguanylate cyclase YeaJ relieves mouse mammary gland pathological damage by changing E. coli phenotypic and host STING-dependent innate immunity responses. YeaJ decreases mammary gland circular vacuoles, bleeding, and degeneration in mice. In addition, YeaJ participates in STING-IRF3 signaling to regulate inflammation in vivo. In vitro, YeaJ decreases damage to macrophages (RAW264.7) but not to mouse mammary epithelial cells (EpH4-Ev). Consistent with the results in mouse mammary glands, YeaJ significantly activates the STING/TBK1/IRF3 pathway in RAW264.7 macrophages as well. In conclusion, the deletion of yeaJ facilitates E. coli NJ17 escape from STING-dependent innate immunity recognition in vitro and in vivo. This study highlights a novel role for YeaJ in E. coli infection, which provides a better understanding of host-bacterium interactions and potential prophylactic strategies for infections. IMPORTANCE E. coli is the etiological agent of environmental mastitis in dairy cows, which causes massive financial losses worldwide. However, the pathophysiological role of YeaJ in the interaction between E. coli and host remains unclear. We found that YeaJ significantly influences various biological characteristics and suppresses severe inflammatory response as well as greater damage. YeaJ alleviates damage to macrophages (RAW264.7) and mouse mammary gland. Moreover, these effects of YeaJ are achieved at least partial by mediating the STING-IRF3 signaling pathway. In conclusion, the deletion of yeaJ facilitates E. coli NJ17 escape from STING-dependent innate immunity recognition in vitro and in vivo. This study is the basis for further research to better understand host-bacterium interactions and provides potential prophylactic strategies for infections.
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Células Epiteliales/microbiología , Proteínas de Escherichia coli/metabolismo , Escherichia coli/inmunología , Escherichia coli/metabolismo , Macrófagos/microbiología , Liasas de Fósforo-Oxígeno/metabolismo , Animales , Biopelículas/crecimiento & desarrollo , Adhesión Celular , Proteínas de Escherichia coli/genética , Femenino , Regulación Bacteriana de la Expresión Génica/inmunología , Glándulas Mamarias Animales/citología , Ratones , Movimiento , Mutación , Liasas de Fósforo-Oxígeno/genética , Células RAW 264.7RESUMEN
Metabolic alterations occur in pathogenic infections, but the role of lipid metabolism in the progression of bacterial mastitis is unclear. Cross talk between lipid droplets (LDs) and invading bacteria occurs, and targeting of de novo lipogenesis inhibits pathogen reproduction. In this study, we investigate the role(s) of lipid metabolism in mammary cells during Streptococcus uberis infection. Our results indicate that S. uberis induces the synthesis of fatty acids and production of LDs. Importantly, taurine reduces fatty acid synthesis, the abundance of LDs and the in vitro bacterial load of S. uberis These changes are mediated, at least partly, by the E3 ubiquitin ligase IDOL, which is associated with the degradation of low-density lipoprotein receptors (LDLRs). We have identified a critical role for IDOL-mediated fatty acid synthesis in bacterial infection, and we suggest that taurine may be an effective prophylactic or therapeutic strategy for preventing S. uberis mastitis.
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Infecciones Estreptocócicas/metabolismo , Infecciones Estreptocócicas/microbiología , Streptococcus/efectos de los fármacos , Taurina/farmacología , Ubiquitina-Proteína Ligasas/metabolismo , Ácidos Grasos/metabolismo , Metabolismo de los Lípidos , Proteolisis , Receptores de LDLRESUMEN
BACKGROUND: Fasting C-peptide (FCP) has been shown to play an important role in the pathophysiology of mood disorders including depression and schizophrenia, but it is unknown whether it also predicts post-stroke depression (PSD). This study examined the association between FCP and PSD at 6 months after acute ischemic-stroke onset among Chinese subjects. METHODS: A total of 656 stroke patients were consecutively recruited from three hospitals of Wuhan city, Hubei province. Clinical and laboratory data were collected on admission. PSD status was evaluated by DSM-V criteria and 17-item Hamilton Rating Scale for Depression (HAMD-17) at 6 months after acute ischemic stroke. The χ2-test, Mann-Whitney U-test, and t-test were used to check for statistical significance. Multivariate logistic regression model was used to explore independent predictor of PSD. RESULTS: In the univariate analysis, significant differences were found between the PSD and non-PSD groups in terms of FCP level (p = 0.009). After multivariate adjustments, FCP remained a significant independent predictor of PSD, with an adjusted odds ratio of 1.179 (95%CI: 1.040-1.337, p = 0.010). CONCLUSIONS: Higher FCP levels on admission were found to be associated with PSD at 6 months after acute ischemic-stroke onset. For stroke patients, doctors should pay attention to the baseline FCP for screening high-risk PSD in clinical practice.
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Isquemia Encefálica , Accidente Cerebrovascular , Isquemia Encefálica/complicaciones , Isquemia Encefálica/epidemiología , Péptido C , Depresión/epidemiología , Depresión/etiología , Ayuno , Humanos , Estudios Prospectivos , Accidente Cerebrovascular/complicacionesRESUMEN
BACKGROUND: Exploring etiological clues to adolescent depression, especially in female adolescents, might be helpful to improve the social environment of female adolescents. The aim at this study is to explore psycho-social factors of female adolescents with high depressive symptomatology and gender differences in depressive symptoms among Chinese adolescents. METHOD: We examined 4100 adolescents from Wuhan city and Jianli county via a cross-sectional study. Depressive symptomatology was screened through the Chinese version of Center for Epidemiology Studies Depression Scale. Multivariate logistic regression was performed to explore the factors related to high depressive symptomatology in female and male adolescents, respectively. RESULTS: The prevalence of high depressive symptomatology in female and male were 38.9 and 30.2% respectively. The psycho-social factors of high depressive symptomatology in female adolescents were age (Adjusted odds ratio [aOR] = 1.201, 95% confidence interval [CI], 1.076 ~ 1.341), single parent family (aOR = 2.004, 95%CI, 1.448 ~ 2.772) and fathers' education level (compared to primary school and below, [Junior middle school, aOR = 0.641, 95%CI, 0.439 ~ 0.934; Senior middle school, aOR = 0.603, 95%CI, 0.410 ~ 0.888; College degree and above, aOR = 0.639, 95%CI, 0.437 ~ 0.936]). CONCLUSION: Fathers' education level was associated with high depressive symptomatology in female adolescents. Female adolescents whose father with primary school education or below deserves more attention. Further epidemiologic researches need to be conducted to explore the different risk factors between female and male adolescents in China.
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Depresión , Caracteres Sexuales , Adolescente , China/epidemiología , Estudios Transversales , Depresión/epidemiología , Femenino , Humanos , Masculino , Factores SocialesRESUMEN
ABSTRACT: Cerebral fat embolism following facial autologous fat injection is a rare and serious complication. There are limited long-term follow-up data on the motion, cognitive and mental outcomes of surviving patients with cerebral fat embolism following facial autologous fat injection. In this study, the authors reported a patient with a 22-year-old woman with a massive right hemisphere infarction following facial autologous fat injection had normal cognitive function, independent living ability, and social function at 5 years follow-up visit, even though computed tomography showed her entire right cerebral hemisphere had atrophied with softening lesions.
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Tejido Adiposo , Embolia Grasa , Tejido Adiposo/trasplante , Adulto , Cara , Femenino , Humanos , Infarto/diagnóstico por imagen , Infarto/etiología , Trasplante Autólogo , Adulto JovenRESUMEN
BACKGROUND: The prognosis of patients with advanced schistosomiasis is poor. Pre-existing prognosis studies did not differentiate the causes of the deaths. The objectives were to evaluate the 2-year overall survival (OS) and advanced schistosomiasis-specific survival (ASS) in patients with advanced schistosomiasis after discharge through competing risk analysis and to build predictive nomograms. METHODS: Data was extracted from a previously constructed database from Hubei province. Patients were enrolled from September 2014 to January 2015, with follow up to January 2017. OS and ASS were primary outcome measures. Nomograms for estimating 2-year OS and ASS rates after discharge were established based on univariate and multivariate Cox regression model and Fine and Gray's model. Their predictive performances were evaluated using C-index and validated in both internal and external validation cohorts. RESULTS: The training cohort included 1487 patients with advanced schistosomiasis. Two-year mortality rate of the training cohort was 8.27% (123/1487). Competing events accounted for 26.83% (33/123). Older age, splemomegaly clinical classification, abnormal serum DBil, AST, ALP and positive HBsAg were significantly associated with 2-year OS. Older age, splemomegaly clinical classification, abnormal serum AST, ALP and positive HBsAg were significantly associated with 2-year ASS. The established nomograms were well calibrated, and had good discriminative ability, with a C-index of 0.813 (95% CI 0.803-0.823) for 2-year OS prediction and 0.834 (95% CI 0.824-0.844) for 2-year ASS prediction. Their predictive performances were well validated in both internal and external validation cohorts. CONCLUSION: The effective predictors of 2-year OS and ASS were discovered through competing risk analysis. The nomograms could be used as convenient predictive tools in clinical practice to guide follow-up and aid accurate prognostic assessment.
Asunto(s)
Nomogramas , Esquistosomiasis , Anciano , Humanos , Alta del Paciente , Pronóstico , Medición de Riesgo , Programa de VERF , Análisis de SupervivenciaRESUMEN
BACKGROUND: For large hemispheric infarction (LHI), malignant cerebral edema (MCE) is a life-threatening complication with a mortality rate approaching 80%. Establishing a convenient prediction model of MCE after LHI is vital for the rapid identification of high-risk patients as well as for a better understanding of the potential mechanism underlying MCE. METHODS: One hundred forty-two consecutive patients with LHI within 24 h of onset between January 1, 2016 and August 31, 2019 were retrospectively reviewed. MCE was defined as patient death or received decompressive hemicraniectomy (DHC) with obvious mass effect (≥ 5 mm midline shift or Basal cistern effacement). Binary logistic regression was performed to identify independent predictors of MCE. Independent prognostic factors were incorporated to build a dynamic nomogram for MCE prediction. RESULTS: After adjusting for confounders, four independent factors were identified, including previously known atrial fibrillation (KAF), midline shift (MLS), National Institutes of Health Stroke Scale (NIHSS) and anterior cerebral artery (ACA) territory involvement. To facilitate the nomogram use for clinicians, we used the "Dynnom" package to build a dynamic MANA (acronym for MLS, ACA territory involvement, NIHSS and KAF) nomogram on web ( http://www.MANA-nom.com ) to calculate the exact probability of developing MCE. The MANA nomogram's C-statistic was up to 0.887 ± 0.041 and the AUC-ROC value in this cohort was 0.887 (95%CI, 0.828 ~ 0.934). CONCLUSIONS: Independent MCE predictors included KAF, MLS, NIHSS, and ACA territory involvement. The dynamic MANA nomogram is a convenient, practical and effective clinical decision-making tool for predicting MCE after LHI in Chinese patients.