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INTRODUCTION: Recent studies have implicated acetyl-L-carnitine as well as other acylcarnitines in depression. To our knowledge, no untargeted metabolomics studies have been conducted among US mainland Puerto Ricans. OBJECTIVES: We conducted untargeted metabolomic profiling on plasma from 736 participants of the Boston Puerto Rican Health Study. METHODS: Using Weighted Gene Co-expression Network Analysis, we identified metabolite modules associated with depressive symptomatology, assessed via the Center for Epidemiologic Studies Depression scale. We identified metabolites contributing to these modules and assessed the relationship between these metabolites and depressive symptomatology. RESULTS: 621 annotated metabolites clustered into eight metabolite modules, of which one, the acylcarnitine module, was significantly inversely associated with depressive symptomatology (ß = - 27.7 (95% CI (- 54.5-0.8); p = 0.043). Several metabolite hub features in the acylcarnitine module were significantly associated with depressive symptomatology, after correction for multiple comparisons. CONCLUSIONS: In this untargeted plasma metabolomics study among mainland Puerto Rican older adults, acylcarnitines, as a metabolite module were inversely associated with depressive symptomatology.
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Carnitina , Depresión , Metabolómica , Humanos , Carnitina/análogos & derivados , Carnitina/sangre , Carnitina/metabolismo , Femenino , Masculino , Depresión/sangre , Depresión/metabolismo , Metabolómica/métodos , Persona de Mediana Edad , Anciano , Puerto Rico , Estudios de Cohortes , Hispánicos o Latinos , Boston/epidemiologíaRESUMEN
The substantial waste of perishable foods during transportation significantly contributes to greenhouse gas emissions, intensifying the climate crisis. To mitigate the rapid spoilage of fruits, an eco-friendly bilayer film was developed using natural egg white (EW), amylose (Am), and tannic acid (TA). The EW/Am-TA bilayer film features a primary layer of amphiphilic EW, ensuring a uniform coating on hydrophobic fruit surfaces, and a secondary layer composed of Am and TA, imparting notable tensile strength (5.3 ± 0.5 MPa) and elongation at break (28.5 ± 4.1 %). This bilayer film effectively shields fruits from UV-B and UV-C radiation (~0 % transmittance at 280 and 330 nm) and exhibits antioxidant and antibacterial properties due to the presence of TA. Fruits such as bananas, avocados, and cherry tomatoes, when dip-coated with the optimized EW/Am-TA bilayer, maintained their freshness, color, weight, and texture for up to seven days, demonstrating the effectiveness of this bilayer coating in food preservation. The natural materials in the coated film are edible and can be safely removed with tap water at room temperature in <10 s, posing no food safety risks. Thus, the proposed bilayer coating presents a significant solution to the global problem of food waste.
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Amilosa , Clara de Huevo , Conservación de Alimentos , Frutas , Taninos , Conservación de Alimentos/métodos , Frutas/química , Taninos/química , Amilosa/química , Clara de Huevo/química , Antioxidantes/química , Películas Comestibles , Antibacterianos/química , Antibacterianos/farmacología , Embalaje de Alimentos/métodosRESUMEN
PURPOSE: Prostate cancer (PCa) is a major urological disease that is associated with significant morbidity and mortality in men. LLGL2 is the mammalian homolog of Lgl. It acts as a tumor suppressor in breast and hepatic cancer. However, the role of LLGL2 and the underlying mechanisms in PCa have not yet been elucidated. Here, we investigate the role of LLGL2 in the regulation of epithelial-mesenchymal transition (EMT) in PCa through autophagy in vitro and in vivo. METHODS: PC3 cells were transfected with siLLGL2 or plasmid LLGL2 and autophagy was examined. Invasion, migration, and wound healing were assessed in PC3 cells under autophagy regulation. Tumor growth was evaluated using a shLLGL2 xenograft mouse model. RESULTS: In patients with PCa, LLGL2 levels were higher with defective autophagy and increased EMT. Our results showed that the knockdown of LLGL2 induced autophagy flux by upregulating Vps34 and ATG14L. LLGL2 knockdown inhibits EMT by upregulating E-cadherin and downregulating fibronectin and α-SMA. The pharmacological activation of autophagy by rapamycin suppressed EMT, and these effects were reversed by 3-methyladenine treatment. Interestingly, in a shLLGL2 xenograft mouse model, tumor size and EMT were decreased, which were improved by autophagy induction and worsened by autophagy inhibition. CONCLUSION: Defective expression of LLGL2 leads to attenuation of EMT due to the upregulation of autophagy flux in PCa. Our results suggest that LLGL2 is a novel target for alleviating PCa via the regulation of autophagy.
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Autofagia , Transición Epitelial-Mesenquimal , Neoplasias de la Próstata , Animales , Humanos , Masculino , Ratones , Autofagia/fisiología , Autofagia/genética , Línea Celular Tumoral , Movimiento Celular/genética , Transición Epitelial-Mesenquimal/genética , Silenciador del Gen , Ratones Desnudos , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/metabolismo , Proteínas Supresoras de Tumor/genética , Proteínas Supresoras de Tumor/metabolismoRESUMEN
Acute rejection (AR) is critical for long-term graft survival in kidney transplant recipients (KTRs). This study aimed to evaluate the efficacy of the integrated risk score of omics-based biomarkers in predicting AR in KTRs. This prospective, randomized, controlled, multicenter, pilot study enrolled 40 patients who recently underwent high-immunologic-risk kidney transplantation (KT). Five omics biomarkers were measured, namely, blood mRNA (three-gene signature), urinary exosomal miRNA (three-gene signature), urinary mRNA (six-gene signature), and two urinary exosomal proteins (hemopexin and tetraspanin-1) at 2 weeks and every 4 weeks after KT for 1 year. An integrated risk score was generated by summing each biomarker up. The biomarker group was informed about the integrated risk scores and used to adjust immunosuppression, but not the control group. The outcomes were graft function and frequency of graft biopsy. Sixteen patients in the biomarker group and nineteen in the control group completed the study. The mean estimated glomerular filtration rate after KT did not differ between the groups. Graft biopsy was performed in two patients (12.5%) and nine (47.4%) in the biomarker and control groups, respectively, with the proportion being significantly lower in the biomarker group (p = 0.027). One patient (6.3%) in the biomarker group and two (10.5%) in the control group were diagnosed with AR, and the AR incidence did not differ between the groups. The tacrolimus trough level was significantly lower in the biomarker group than in the control group at 1 year after KT (p = 0.006). Integrated omics biomarker monitoring may help prevent unnecessary or high-complication-risk biopsy and enables tailored immunosuppression by predicting the risk of AR in KTRs.
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Biomarcadores , Rechazo de Injerto , Trasplante de Riñón , Humanos , Trasplante de Riñón/efectos adversos , Rechazo de Injerto/diagnóstico , Rechazo de Injerto/sangre , Masculino , Femenino , Biomarcadores/sangre , Biomarcadores/orina , Proyectos Piloto , Persona de Mediana Edad , Estudios Prospectivos , Adulto , Factores de Riesgo , Supervivencia de Injerto , MicroARNs/sangre , MicroARNs/genética , Medición de RiesgoRESUMEN
CONTEXT: High school football remains a popular, physically demanding sport despite the known risks for acute brain and neck injury. Impacts to the head also raise concerns about their cumulative effects and long-term health consequences. OBJECTIVE: To examine the effectiveness of a helmetless tackling training program to reduce head impact exposure in football participants. DESIGN: A three-year, quasi-experimental, prospective cohort (clinicaltrials.gov #NCTXXX) study. SETTING: Honolulu (XXX, XXX) area public and private secondary schools with varsity and junior varsity football. PATIENTS OR OTHER PARTICIPANTS: Football participants (n=496) ages 14 to 18 years old. Intervention(s) Participants wore new football helmets furnished with head impact sensor technology. Teams employed a season-long helmetless tackling and blocking intervention in Years 2 and 3 consisting of a 3-phase, systematic progression of 10 instructional drills. MAIN OUTCOME MEASURE(S): Head impact frequency per athlete exposure (ImpAE), location, and impact magnitude per participant intervention adherence levels (60% and 80%). RESULTS: An overall regression analysis revealed a significant negative association between ImpAE and adherence (p=0.003, beta=-1.21, SE=0.41). In year 3, a longitudinal data analysis of weekly ImpAE data resulted in an overall difference between the adherent and non-adherent groups (p=0.040 at 80%; p=0.004 at 60%), mainly due to decreases in top and side impacts. Mean cumulative impact burden for the adherent group (n=131: 2,105.84g ± 219.76,) was significantly (p=0.020) less than the non-adherent group (n=90: 3,158.25g ± 434.80) at the 60% adherence level. CONCLUSIONS: Participants adhering to the intervention on at least a 60% level experienced a 34% to 37% significant reduction in the number of head impacts (per exposure) through the season. These results provide additional evidence that a helmetless tackling and blocking training intervention (utilizing the HuTT® program) reduces head impact exposure in high school football players. Adherence to an intervention is crucial for achieving intended outcomes.
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PURPOSE: To evaluate the efficacy of inverted internal limiting membrane (ILM) flap technique in full-thickness macular holes (MHs) with a size of ≤400 µm compared to the ILM peeling technique. METHODS: Related literatures that compared inverted ILM flap and ILM peeling in MHs ≤ 400 µm were reviewed by searching electronic databases including Pubmed, EMbase, ClinicalTrials.gov, and Cochrane Library up to April 2023. The primary outcome measure was hole closure rate, and the secondary outcome measures were the mean postoperative best-corrected visual acuity (BCVA), retinal sensitivity, and outer status of the retinal layers, including the external limiting membrane and ellipsoid zone. The quality of the articles was assessed according to the revised version of the Cochrane risk-of-bias tool for randomized trials or the Newcastle-Ottawa scale. In the case of heterogeneity, a sensitivity analysis was conducted, and publication bias was visually evaluated using a funnel plot. RESULTS: This review included six studies with 610 eyes for the primary outcome and 385 eyes for the secondary outcomes, which were two randomized control trials and four retrospective studies. Pooled data revealed that the overall MH closure rate was 99.4% in the inverted ILM flap group and 96.2% in the ILM peeling group, without significant difference between the two groups (odds ratio = 3.91; 95% confidence interval, 0.82~18.69; P = 0.09). The inverted ILM flap technique did not have a favorable effect on the BCVA, retinal sensitivity, or recovery of the outer retinal layers. These results were consistent with those of the subgroup analysis of the different follow-up periods. No significant publication bias was observed. CONCLUSION: In eyes with MHs of ≤400 µm, both techniques demonstrated excellent surgical outcomes without significant differences. Therefore, surgical techniques can be selected according to surgeon preferences.
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Perforaciones de la Retina , Colgajos Quirúrgicos , Perforaciones de la Retina/cirugía , Humanos , Agudeza Visual , Vitrectomía/métodos , Resultado del TratamientoRESUMEN
Background: Recent studies have identified plasma metabolites associated with cognitive decline and Alzheimer's disease; however, little research on this topic has been conducted in Latinos, especially Puerto Ricans. Objective: This study aims to add to the growing body of metabolomics research in Latinos to better understand and improve the health of this population. Methods: We assessed the association between plasma metabolites and global cognition over 12 years of follow-up in 736 participants of the Boston Puerto Rican Health Study (BPRHS). Metabolites were measured with untargeted metabolomic profiling (Metabolon, Inc) at baseline. We used covariable adjusted linear mixed models (LMM) with a metaboliteâ*âtime interaction term to identify metabolites (of 621 measured) associated with â¼12 years cognitive trajectory. Results: We observed strong inverse associations between medium-chain fatty acids, caproic acid, and the dicarboxylic acids, azelaic and sebacic acid, and global cognition. N-formylphenylalanine, a tyrosine pathway metabolite, was associated with improvement in cognitive trajectory. Conclusions: The metabolites identified in this study are generally consistent with prior literature and highlight a role medium chain fatty acid and tyrosine metabolism in cognitive decline.
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Disfunción Cognitiva , Hispánicos o Latinos , Metabolómica , Humanos , Disfunción Cognitiva/sangre , Femenino , Masculino , Anciano , Persona de Mediana Edad , Estudios de Cohortes , Puerto Rico/etnología , Estudios de SeguimientoRESUMEN
African swine fever virus (ASFV) is the causative agent of the highly lethal African swine fever disease that affects domestic pigs and wild boars. In spite of the rapid spread of the virus worldwide, there is no licensed vaccine available. The lack of a suitable cell line for ASFV propagation hinders the development of a safe and effective vaccine. For ASFV propagation, primary swine macrophages and monocytes have been widely studied. However, obtaining these cells can be time-consuming and expensive, making them unsuitable for mass vaccine production. The goal of this study was to validate the suitability of novel CA-CAS-01-A (CAS-01) cells, which was identified as a highly permissive cell clone for ASFV replication in the MA-104 parental cell line for live attenuated vaccine development. Through a screening experiment, maximum ASFV replication was observed in the CAS-01 cell compared to other sub-clones of MA-104 with 14.89 and log10 7.5 ± 0.15 Ct value and TCID50/ml value respectively. When CAS-01 cells are inoculated with ASFV, replication of ASFV was confirmed by Ct value for ASFV DNA, HAD50/ml assay, TCID50/ml assay, and cytopathic effects and hemadsoption were observed similar to those in primary porcine alveolar macrophages after 5th passage. Additionally, we demonstrated stable replication and adaptation of ASFV over the serial passage. These results suggest that CAS-01 cells will be a valuable and promising cell line for ASFV isolation, replication, and development of live attenuated vaccines.
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Virus de la Fiebre Porcina Africana , Fiebre Porcina Africana , Porcinos , Animales , Virus de la Fiebre Porcina Africana/genética , Fiebre Porcina Africana/prevención & control , Vacunas Atenuadas/genética , Proteínas Virales/genética , Sus scrofa , Desarrollo de Vacunas , Línea CelularRESUMEN
Introduction: Conventional foot-and-mouth disease (FMD) vaccines have been developed to enhance their effectiveness; however, several drawbacks remain, such as slow induction of antibody titers, short-lived immune response, and local side effects at the vaccination site. Therefore, we created a novel FMD vaccine that simultaneously induces cellular and humoral immune responses using the Dectin-2 agonist, D-galacto-D-mannan, as an adjuvant. Methods: We evaluated the innate and adaptive (cellular and humoral) immune responses elicited by the novel FMD vaccine and elucidated the signaling pathway involved both in vitro and in vivo using mice and pigs, as well as immune cells derived from these animals. Results: D-galacto-D-mannan elicited early, mid-, and long-term immunity via simultaneous induction of cellular and humoral immune responses by promoting the expression of immunoregulatory molecules. D-galacto-D-mannan also enhanced the immune response and coordinated vaccine-mediated immune response by suppressing genes associated with excessive inflammatory responses, such as nuclear factor kappa B, via Sirtuin 1 expression. Conclusion: Our findings elucidated the immunological mechanisms induced by D-galacto-D-mannan, suggesting a background for the robust cellular and humoral immune responses induced by FMD vaccines containing D-galacto-D-mannan. Our study will help to facilitate the improvement of conventional FMD vaccines and the design of next-generation FMD vaccines.
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Adyuvantes de Vacunas , Lectinas Tipo C , Vacunas Virales , Animales , Ratones , Porcinos , Inmunidad Humoral , Mananos , Adyuvantes Inmunológicos , Adyuvantes FarmacéuticosRESUMEN
BACKGROUND: This study aims to assess the effectiveness of the preoperative flash visual evoked potential (VEP) test in predicting postoperative visual acuity for monocular mature cataract cases when compared to the contralateral normal eye. METHODS: The study included 60 patients, each with a monocular mature cataract diagnosis, who underwent preoperative flash VEP testing showing no pattern VEP response. Subsequently, phacoemulsification was performed. The relationship between the flash VEP test latency values (P1, N2, P2) and amplitude value (N2-P2), and the degree of visual acuity recovery 3 months post-cataract surgery, was evaluated using the LogMAR scale. Furthermore, a linear regression analysis was conducted to explore the connection between preoperative flash VEP components and postoperative visual acuity. RESULTS: The average age of the patients was 65.4 ± 13.6 years, with a range of 43 to 87 years. The study included 36 males and 24 females. A significant disparity in visual acuity was observed between the preoperative and 3-month postoperative stages (p < 0.001). The preoperative flash VEP test for mature cataracts revealed significant delays in P1, N2, and P2 latency, as well as a reduction in N2-P2 amplitude potential when compared to the contralateral normal eye (p < 0.001). Notably, delayed P2 latency and reduced N2-P2 amplitude potential were particularly indicative of poor visual acuity prognosis after cataract surgery in the multiple regression analysis (p < 0.05). The N2-P2 amplitude potential was the important value that exhibited statistically significant results, with an area under the curve (AUC) of 80% sensitivity and 88% specificity, using a cutoff value of 6.07 µV. CONCLUSIONS: In cases of monocular mature cataract, a reduction in N2-P2 amplitude potential compared to the contralateral normal eye emerged as the most reliable predictor of postoperative visual prognosis following cataract surgery.
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Catarata , Potenciales Evocados Visuales , Agudeza Visual , Humanos , Potenciales Evocados Visuales/fisiología , Masculino , Femenino , Anciano , Agudeza Visual/fisiología , Catarata/fisiopatología , Persona de Mediana Edad , Anciano de 80 o más Años , Adulto , Facoemulsificación , Cuidados Preoperatorios/métodos , Estimulación Luminosa , Estudios de Seguimiento , Curva ROC , Estudios Retrospectivos , Periodo PreoperatorioRESUMEN
Tight control of the type I interferon (IFN) signaling pathway is critical for maintaining host innate immune responses, and the ubiquitination and deubiquitination of signaling molecules are essential for signal transduction. Deubiquitinase ubiquitin-specific protein 19 (USP19) is known to be involved in deubiquitinating Beclin1, TRAF3, and TRIF for downregulation of the type I IFN signaling. Here, we show that SIAH1, a cellular E3 ubiquitin ligase that is involved in multicellular pathway, is a potent positive regulator of virus-mediated type I IFN signaling that maintains homeostasis within the antiviral immune response by targeting USP19. In the early stages of virus infection, stabilized SIAH1 directly interacts with the USP19 and simultaneously mediates K27-linked ubiquitination of 489, 490, and 610 residues of USP19 for proteasomal degradation. Additionally, we found that USP19 specifically interacts with MAVS and deubiquitinates K63-linked ubiquitinated MAVS for negative regulation of type I IFN signaling. Ultimately, we identified that SIAH1-mediated degradation of USP19 reversed USP19-mediated deubiquitination of MAVS, Beclin1, TRAF3, and TRIF, resulting in the activation of antiviral immune responses. Taken together, these findings provide new insights into the molecular mechanism of USP19 and SIAH1, and suggest a critical role of SIAH1 in antiviral immune response and homeostasis.
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Interferón Tipo I , Ubiquitina , Humanos , Ubiquitina/metabolismo , Factor 3 Asociado a Receptor de TNF/genética , Beclina-1 , Ubiquitinación , Inmunidad Innata , Interferón Tipo I/metabolismo , Enzimas Desubicuitinizantes/genética , Enzimas Desubicuitinizantes/metabolismo , Proteínas Adaptadoras del Transporte Vesicular , Endopeptidasas/genética , Endopeptidasas/metabolismoRESUMEN
DP96R of African swine fever virus (ASFV), also known as uridine kinase (UK), encodes a virulence-associated protein. Previous studies have examined DP96R along with other genes in an effort to create live attenuated vaccines. While experiments in pigs have explored the impact of DP96R on the pathogenicity of ASFV, the precise molecular mechanism underlying this phenomenon remains unknown. Here, we describe a novel molecular mechanism by which DP96R suppresses interferon regulator factor-3 (IRF3)-mediated antiviral immune responses. DP96R interacts with a crucial karyopherin (KPNA) binding site within IRF3, disrupting the KPNA-IRF3 interaction and consequently impeding the translocation of IRF3 to the nucleus. Under this mechanistic basis, the ectopic expression of DP96R enhances the replication of DNA and RNA viruses by inhibiting the production of IFNs, whereas DP96R knock-down resulted in higher IFNs and IFN-stimulated gene (ISG) transcription during ASFV infection. Collectively, these findings underscore the pivotal role of DP96R in inhibiting IFN responses and increase our understanding of the relationship between DP96R and the virulence of ASFV.
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Virus de la Fiebre Porcina Africana , Factor 3 Regulador del Interferón , Animales , Virus de la Fiebre Porcina Africana/genética , Virus de la Fiebre Porcina Africana/patogenicidad , Interferones/metabolismo , Porcinos , Proteínas Virales/metabolismo , Virulencia , Factores de Virulencia/genética , Factor 3 Regulador del Interferón/metabolismo , Humanos , Interferón Tipo I/metabolismoRESUMEN
Objective: Several studies have examined metabolomic profiles in relation to Alzheimer's disease and related dementia (AD/ADRD) risk; however, few studies have focused on minorities, such as Latinos, or examined Magnetic-Resonance Imaging (MRI)-based outcomes. Methods: We used multiple linear regression, adjusted for covariates, to examine the association between metabolite concentration and MRI-derived brain age deviation. Metabolites were measured at baseline with untargeted metabolomic profiling (Metabolon, Inc). Brain age deviation (BAD) was calculated at wave 4 (~ 9 years from Boston Puerto Rican Health Study (BPRHS) baseline) as chronologic age, minus MRI-estimated brain age, representing the rate of biological brain aging relative to chronologic age. We also examined if metabolites associated with BAD were similarly associated with hippocampal volume and global cognitive function at wave 4 in the BPRHS. Results: Several metabolites, including isobutyrylcarnitine, propionylcarnitine, phenylacetylglutamine, phenylacetylcarnitine (acetylated peptides), p-cresol-glucuronide, phenylacetylglutamate, and trimethylamine N-oxide (TMAO) were inversely associated with brain age deviation. Taurocholate sulfate, a bile salt, was marginally associated with better brain aging. Most metabolites with negative associations with brain age deviation scores also were inversely associations with hippocampal volumes and wave 4 cognitive function. Conclusion: The metabolites identifiedin this study are generally consistent with prior literature and highlight the role of BCAA, TMAO and microbially derived metabolites in cognitive decline.
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This study investigated the role of the axis involving chemokine receptor 6 (CCR6) and its ligand chemokine (C-C motif) ligand 20 (CCL20) in acute kidney disease (AKD) using an ischemia-reperfusion injury (IRI) model. The model was established by clamping the unilateral renal artery pedicle of C57BL/6 mice for 30 min, followed by evaluation of CCL20/CCR6 expression at 4 weeks post-IRI. In vitro studies were conducted to examine the effects of hypoxia and H2 O2 -induced oxidative stress on CCL20/CCR6 expression in kidney tissues of patients with AKD and chronic kidney disease (CKD). Tubular epithelial cell apoptosis was more severe in C57BL/6 mice than in CCL20 antibody-treated mice, and CCR6, NGAL mRNA, and IL-8 levels were higher under hypoxic conditions. CCL20 blockade ameliorated apoptotic damage in a dose-dependent manner under hypoxia and reactive oxygen species injury. CCR6 expression in IRI mice indicated that the disease severity was similar to that in patients with the AKD phenotype. Morphometry of CCL20/CCR6 expression revealed a higher likelihood of CCR6+ cell presence in CKD stage 3 patients than in stage 1-2 patients. Kidney tissues of patients with CKD frequently contained CCL20+ cells, which were positively correlated with interstitial inflammation. CCL20/CCR6 levels were increased in fibrotic kidneys at 4 and 8 weeks after 5/6 nephrectomy. These findings suggest that modulating the CCL20/CCR6 pathway is a potential therapeutic strategy for managing the progression of AKD to CKD.
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Lesión Renal Aguda , Insuficiencia Renal Crónica , Humanos , Animales , Ratones , Ratones Endogámicos C57BL , Ligandos , Riñón , Células Epiteliales , Arteria Renal , Hipoxia , Receptores CCR6/genética , Quimiocina CCL20/genéticaRESUMEN
BACKGROUND: In hallux valgus surgery, it is essential to accurately assess the position of the sesamoids both pre- and postoperatively. Weight-bearing foot anteroposterior, tangential sesamoid, and semi-weight-bearing computed tomography axial views are radiographic methods used to assess the medial sesamoid position. This study aimed to measure the medial sesamoid position and evaluate the correlation between these three radiographic methods. METHODS: This retrospective study comprised 59 feet from 49 patients who underwent hallux valgus surgery. The mean age of patients was 54.6 (range, 22-70) years. We took preoperative and postoperative measurements using the weight-bearing anteroposterior, tangential sesamoid, and semi-weight-bearing computed tomography axial views to assess the medial sesamoid position. RESULTS: The mean grades of the medial sesamoid position preoperatively and 6 months postoperatively were 2.5 and 0.8, 1.6 and 0.4, and 1.3 and 0.3 points based on the anteroposterior, tangential sesamoid, and computed tomography axial views, respectively (P < 0.001). Preoperatively, there was a strong positive correlation between the computed tomography axial and tangential sesamoid views (P < 0.001, r = 0.645) and anteroposterior and computed tomography axial views (P < 0.001, r = 0.468). In contrast, the tangential sesamoid and anteroposterior views showed a weak positive correlation (P = 0.03, r = 0.283). Six months postoperatively, there was a positive correlation between the computed tomography axial and tangential sesamoid views (P < 0.001, r = 0.473), anteroposterior and computed tomography axial views (P < 0.001, r = 0.470), and tangential sesamoid and anteroposterior views (P < 0.001, r = 0.480). CONCLUSIONS: We observed that the anteroposterior view exhibited a higher degree of medial sesamoid position displacement than the computed tomography axial and tangential sesamoid views. For the preoperative evaluation of the medial sesamoid position, the correlation between the computed tomography axial and tangential sesamoid views was stronger than that between the tangential sesamoid and anteroposterior views. However, all three views showed strong correlations postoperatively.
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Hallux Valgus , Hallux , Huesos Metatarsianos , Huesos Sesamoideos , Humanos , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Hallux Valgus/diagnóstico por imagen , Hallux Valgus/cirugía , Estudios Retrospectivos , Huesos Sesamoideos/diagnóstico por imagen , Huesos Sesamoideos/cirugía , Tomografía Computarizada por Rayos X , Cuidados Preoperatorios , Huesos Metatarsianos/cirugíaRESUMEN
Avian influenza is a serious threat to both public health and the poultry industry worldwide. This respiratory virus can be combated by eliciting robust immune responses at the site of infection through mucosal immunization. Recombinant probiotics, specifically lactic acid bacteria, are safe and effective carriers for mucosal vaccines. In this study, we engineered recombinant fusion protein by fusing the hemagglutinin 1 (HA1) subunit of the A/Aquatic bird/Korea/W81/2005 (H5N2) with the Bacillus subtilis poly γ-glutamic acid synthetase A (pgsA) at the surface of Lactobacillus casei (pgsA-HA1/L. casei). Using subcellular fractionation and flow cytometry we confirmed the surface localization of this fusion protein. Mucosal administration of pgsA-HA1/L. casei in mice resulted in significant levels of HA1-specific serum IgG, mucosal IgA and neutralizing antibodies against the H5N2 virus. Additionally, pgsA-HA1/L. casei-induced systemic and local cell-mediated immune responses specific to HA1, as evidenced by an increased number of IFN-γ and IL-4 secreting cells in the spleens and higher levels of IL-4 in the local lymphocyte supernatants. Finally, mice inoculated with pgsA-HA1/L. casei were protected against a 10LD50 dose of the homologous mouse-adapted H5N2 virus. These results suggest that mucosal immunization with L. casei displaying HA1 on its surface could be a potential strategy for developing a mucosal vaccine against other H5 subtype viruses.
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Subtipo H5N2 del Virus de la Influenza A , Virus de la Influenza A , Vacunas contra la Influenza , Lacticaseibacillus casei , Animales , Ratones , Lacticaseibacillus casei/genética , Interleucina-4 , Administración a través de la Mucosa , Inmunidad , Administración OralRESUMEN
Atomically thin 2D transition metal dichalcogenides (TMDs) have recently been spotlighted for next-generation electronic and photoelectric device applications. TMD materials with high carrier mobility have superior electronic properties different from bulk semiconductor materials. 0D quantum dots (QDs) possess the ability to tune their bandgap by composition, diameter, and morphology, which allows for a control of their light absorbance and emission wavelength. However, QDs exhibit a low charge carrier mobility and the presence of surface trap states, making it difficult to apply them to electronic and optoelectronic devices. Accordingly, 0D/2D hybrid structures are considered as functional materials with complementary advantages that may not be realized with a single component. Such advantages allow them to be used as both transport and active layers in next-generation optoelectronic applications such as photodetectors, image sensors, solar cells, and light-emitting diodes. Here, recent discoveries related to multicomponent hybrid materials are highlighted. Research trends in electronic and optoelectronic devices based on hybrid heterogeneous materials are also introduced and the issues to be solved from the perspective of the materials and devices are discussed.
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BACKGROUND: Robotic kidney transplantation (RKT) is a novel and welcomed innovation yielding good surgical outcomes. However, data on the feasibility and safety of performing RKT by surgeons with a lack of prior minimally invasive surgery (MIS) experience are limited. The authors aimed to evaluate the surgical and functional results of RKT and present the learning curves (LC) of RKT by a single surgeon with no prior experience in MIS. MATERIALS AND METHODS: This was a retrospective study of all RKT performed between November 2019 and April 2023 at Severance Hospital in Seoul, South Korea. The authors analyzed surgical and functional outcomes, as well as complication rates of RKT in comparison to open kidney transplantation (OKT). The authors evaluated LCs using the cumulative summation method to describe the number of cases associated with the competency of a single surgeon. RESULTS: A total of 50 patients who underwent RKT and 104 patients who underwent OKT were included in this study. In RKT group, the median surgical console time was 193 min (interquartile range, 172-222) and the median vascular anastomoses time was 38 min (35-44). Total operation time was 323 min (290-371) and rewarming time was 62.5 min (56.0-70.0) in RKT group compared to 210 min (190-239) and 25 min (21-30), respectively, in OKT group. Despite extended surgical durations with a robotic technique, both groups had comparable intraoperative and postoperative outcomes, as well as renal function. Estimated blood loss and post-transplant hospital stays were significantly lower in RKT group than in OKT group. LC analysis of RKT by the single surgeon revealed that surgical competence was achieved after 15 cases. CONCLUSION: Even if surgeons do not have prior experience with MIS, they can rapidly overcome the LC and safely perform RKT with adequate preparation and acquisition of basic robotic surgical techniques.
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Trasplante de Riñón , Procedimientos Quirúrgicos Robotizados , Cirujanos , Humanos , Trasplante de Riñón/métodos , Procedimientos Quirúrgicos Robotizados/efectos adversos , Estudios Retrospectivos , Procedimientos Quirúrgicos Mínimamente Invasivos/efectos adversosRESUMEN
Purpose Prostate cancer (PCa) is a major urological disease that is associated with significant morbidity and mortality in men. LLGL2 is the mammalian homolog of Lgl. It acts as a tumor suppressor in breast and hepatic cancer. However, the role of LLGL2 and the underlying mechanisms in PCa have not yet been elucidated. Here, we investigate the role of LLGL2 in the regulation of epithelial-mesenchymal transition (EMT) in PCa through autophagy in vitro and in vivo. Methods PC3 cells were transfected with siLLGL2 or plasmid LLGL2 and autophagy was examined. Invasion, migration, and wound healing were assessed in PC3 cells under autophagy regulation. Tumor growth was evaluated using a shLLGL2 xenograft mouse model. Results In patients with PCa, LLGL2 levels were higher with defective autophagy and increased EMT. Our results showed that the knockdown of LLGL2 induced autophagy flux by upregulating Vps34 and ATG14L. LLGL2 knockdown inhibits EMT by upregulating E-cadherin and downregulating fibronectin and α-SMA. The pharmacological activation of autophagy by rapamycin suppressed EMT, and these effects were reversed by 3-methyladenine treatment. Interestingly, in a shLLGL2 xenograft mouse model, tumor size and EMT were decreased, which were improved by autophagy induction and worsened by autophagy inhibition. Conclusion Defective expression of LLGL2 leads to attenuation of EMT due to the upregulation of autophagy flux in PCa. Our results suggest that LLGL2 is a novel target for alleviating PCa via the regulation of autophagy.
RESUMEN
Stress granules (SGs) constitute a signaling hub that plays a critical role in type I interferon responses. Here, we report that growth arrest and DNA damage-inducible beta (Gadd45ß) act as a positive regulator of SG-mediated interferon signaling by targeting G3BP upon RNA virus infection. Gadd45ß deficiency markedly impairs SG formation and SG-mediated activation of interferon signaling in vitro. Gadd45ß knockout mice are highly susceptible to RNA virus infection, and their ability to produce interferon and cytokines is severely impaired. Specifically, Gadd45ß interacts with the RNA-binding domain of G3BP, leading to conformational expansion of G3BP1 via dissolution of its autoinhibitory electrostatic intramolecular interaction. The acidic loop 1- and RNA-binding properties of Gadd45ß markedly increase the conformational expansion and RNA-binding affinity of the G3BP1-Gadd45ß complex, thereby promoting assembly of SGs. These findings suggest a role for Gadd45ß as a component and critical regulator of G3BP1-mediated SG formation, which facilitates RLR-mediated interferon signaling.