Troelsencates6384

Influenza is an acute respiratory disease and a global health problem. Although influenza vaccines are commercially available, frequent antigenic changes in hemagglutinin might render them less effective or unavailable. We previously reported that modified outer membrane vesicle (fmOMV) provided immediate and robust protective immunity against various subtypes of influenza virus. However, the effect was transient because it was innate immunity-dependent. In this study, we investigated the effects of consecutive administration of fmOMV and influenza virus on the adaptive immune response and long-term protective immunity against influenza virus. When the mice were pretreated with fmOMV and subsequently infected with influenza virus, strong influenza-specific antibody and T cell responses were induced in both systemic and lung mucosal compartments without pathogenic symptoms. Upon the secondary viral challenge at week 4, the mice given fmOMV and influenza virus exhibited almost complete protection against homologous and heterologous viral challenge. More importantly, this strong protective immunity lasted up to 18 weeks after the first infection. These results show that pretreatment with fmOMV and subsequent infection with influenza virus efficiently induces broad and long-lasting protective immunity against various virus subtypes, suggesting a novel antiviral strategy against newly-emerging viral diseases without suitable vaccines or therapeutics.Choroid plexus epithelial cells (CPEpiCs) determine the composition of cerebrospinal fluid (CSF) and constitute the blood-CSF barrier (BCSFB), functions that are altered in neurodegenerative diseases. In Parkinson's disease (PD) the pathological environment oxidizes and deamidates the ceruloplasmin, a CSF-resident ferroxidase, which undergoes a gain of RGD-recognizing integrin binding property, that may result in signal transduction. We investigated the effects that oxidized/deamidated ceruloplasmin (Cp-ox/de) may exert on CPEpiCs functions. Through RGD-recognizing integrins binding, Cp-ox/de mediates CPEpiCs adhesion and intracellular signaling, resulting in cell proliferation inhibition and alteration of the secretome profile in terms of proteins related to cell-extracellular matrix interaction. Oxidative conditions, comparable to those found in the CSF of PD patients, induced CPEpiCs barrier leakage, allowing Cp-ox/de to cross it, transducing integrins-mediated signal that further worsens BCSFB integrity. This mechanism might contribute to PD pathological processes altering CSF composition and aggravating the already compromised BCSFB function.Although cisplatin is an effective platinum-based anticancer drug against solid cancer, its availability is limited owing to its adverse side effects. Our study aimed to identify the potential relationship within cisplatin-induced multi-organ physiological changes and genetic factors associated with sex differences in nephrotoxicity susceptibility. To investigate this, mice received a single intraperitoneal injection of cisplatin. Cisplatin administration resulted in renal dysfunction, as evidenced by the elevation in serum biomarkers of renal damage (blood urea nitrogen and creatinine) and the degree of histopathological alterations. In particular, along with testicular damage and low testosterone levels, we also observed a decrease in male-specific (CYP3A2) or male-dominant (CYP2B1 and CYP3A1) CYP isoforms in the livers of rats with hepatotoxicity following cisplatin treatment, which may be associated with an imbalance in male hormone regulation caused by renal and testicular injury. Notably, we found that ower in males before cisplatin treatment. Collectively, our comprehensive findings provided valuable insight into the potential mechanisms of sex differences in cisplatin-induced nephrotoxicity susceptibility.

Thoracic aortic aneurysm (TAA) is a highly morbid disease. We have previously shown that baseline hemodynamic measures reflecting aortic function (AoFx) are associated with future TAA expansion. However, whether serial arterial hemodynamic assessment further improves TAA growth assessment remains unknown. Thus, we aimed to compare single vs. serial arterial hemodynamic assessments in the evaluation of future TAA growth.

Eighty-six unoperated participants with TAA underwent non-invasive arterial hemodynamic assessment using arterial tonometry and echocardiography at baseline and after 1-year. Aortic diameter was measured serially with standard imaging modalities. Stepwise multivariable linear regression was used to assess associations of baseline and 1-year change (Δ) in arterial hemodynamic measures with TAA growth.

Mean age was 62.7±11.0 years; 79% were male. Mean±SD aneurysm growth was 0.48±0.54 mm/year after a follow-up of 2.96±1.03 years. Yearly changes in arterial hemodynamic measures ranged from -y suffice, which simplifies its use for potential predictive algorithms.Divided atrium (or Cor triatriatum) dexter (DAD) is a rare congenital cardiopathy, usually associated with other anomalies; isolated forms are even rarer. We report the case of an 84-year-old woman presenting isolated DAD complicated by right-left atrial shunt through patent foramen ovale (PFO) revealed by right cardiac failure and severe hypoxemia. Late destabilization was due to total superior vena cava thrombosis, related to her pace-maker. Given the overall context, completely percutaneous treatment was performed, associating PFO occlusion and stent implantation in the right atrial membrane, providing total symptom regression. Thus, percutaneous correction of DAD appears to be safe and effective.Glycolysis and heat shock proteins (HSPs) play an important role in mediating the physiological response to hypoxia. The changes of glycolysis and HSPs with altitude would provide important information regarding ways to prevent hypoxia-related sickness in both animals and humans. In this study, the expression pattern of HIF1A, PDK4, HSP27 and HSP60, indexes activity and content of glucose metabolism were detected in heart, lung, brain, and quadriceps femoris taken from Tibetan sheep (Ovis aries) that were raised at different altitudes (2,500 m, 3,500 m and 4,500 m). The expression of HIF1A and PDK4 was increased with increasing altitude in all of the tissues. The lactate dehydrogenase (LDH) activities and adenosine triphosphate (ATP), nicotinamide adenine dinucleotide (NADH (redox state), NAD+), lactic acid (LA), pyruvic acid (PA) contents were all increased with increasing altitude in all of the tissues. The ratio of NADH/NAD+ and LA/PA were higher in sheep at an altitude of 4,500 m than of 3,500 m and 2,500 m in all tissues, except for the NADH/NAD+ ratio in lung and quadriceps femoris. An increase in the protein and mRNA expression of ATP-independent HSP27 during hypoxia condition was detected. The expression of ATP-dependent HSP60 mRNA and protein was increased in all of the tissues at an altitude of 3,500 m than of 2,500 m, but was decreased at an altitude of 4,500 m. These results suggest that glycolysis and HSPs are upregulated to ensure energy supply and proteostasis during hypoxia, but energy conservation may be prioritized over cytoprotective protein chaperoning in Tibetan sheep tissues during extreme hypoxia.

Asthma is a common chronic airway inflammatory disease worldwide. Studies on gene expression profiles in induced sputum may provide noninvasive diagnostic biomarkers and therapeutic targets for asthma.

To investigate mRNA expression of MMP12 in induced sputum and its relationship with asthma airway eosinophilic inflammation.

GSE76262 dataset was analyzed using R software, weighted gene coexpression network analysis (WGCNA), and protein-protein interaction (PPI) network construction. The top ten hub genes were screened with Cytoscape software (version 3.8.4). We then verified the mRNA expression of MMP12 in two other datasets (GSE137268 and GSE74075) via ROC curve estimates and our induced sputum samples using real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). Finally, we explored the correlation between MMP12 with asthmatic eosinophilic-related indicators.

We obtained the top ten hub genes, namely, CCL17, CCL2, CSF1, CCL22, CCR3, CD69, FCGR2B, CD1C, CD1E, and MMP12 via etic diagnosis and therapy in the future.The expression profile of early B-cell factor (Ebf) genes and loss of function experiments denote a crucial role for these genes during the late stage of skeletogenesis. However, little is known regarding the expression and function of these genes during the early stage of skeletogenesis. Therefore, this study aimed to detail the spatiotemporal expression pattern of cEbf1, in comparison to cEbf2 and cEbf3, in chick limb buds and investigate its function during chondrogenesis. cEbf1-3 were co-expressed in the distal mesenchyme from a very early stage and later in the outer perichondrium and the surrounding noncartilaginous mesenchymal cells. Ebf1 loss of function through injection of RCASBP virus-carrying Ebf1 dominant-negative form (ΔEbf1) into the wing buds resulted in shortened skeletal elements with a clear defect in the chondrocyte differentiation program. In RCASBP-ΔEbf1 injected wing, the chondrogenesis was initiated normally but hindered at the maturation stage. check details Subsequently, the chondrocytes failed to become mature or hypertrophic and the long bone diaphysis was not properly developed. The final phenotype included shorter, thicker, and fused long bones. These phenotypic changes were associated with downregulation of the early [Sox9 and collagen type II (Col2a1)] and the late [alkaline phosphatase (AP)] chondrocytes differentiation markers in the limb buds. These results conclude that cEbf1 could be involved in a molecular cascade that promotes the terminal stages of chondrogenesis in the long bone anlagen.The "burned out" or "burnt out" testicular cancer (BTC) indicates the spontaneous and complete regression of a testicular germ cell tumor in the presence of distant metastases at the diagnosis. As this condition was never reviewed systematically, a scoping review was conducted to scrutinize the available literature on clinical and histological features of BTC patients. Medline was searched from inception to 19 April 2020. A virtual cohort of 68 BTC patients was generated. Our findings highlighted some inconsistencies BTC was diagnosed in 5,9% of patients not showing distant metastases and in 2,9% of patients who did not undergo an orchiectomy. Besides, evidence of residual tumor was found in 22,7% of testis specimens, recognized as seminoma in 40% of cases. The emerged inconsistencies may derive from the lack of an unequivocal definition of BTC. Larger collaborative studies are needed to define the best diagnostic workup and treatment for BTC patients.

Surgical site infections (SSI) are the second commonest healthcare-associated infections. Active SSI surveillance can help inform preventative measures and assess the impact of these measures.

We aimed to describe the evolution in trends over fourteen years of prospective active SSI surveillance and implementations of SSI prevention measures in a French Teaching Hospital.

We monitored and included in the study all surgical procedures performed from 2003 to 2016 in eight surgical units. The semi-automated surveillance method consisted in weekly collection of SSI declaration forms (pre-filled with patient and procedure administrative data and microbiology laboratory data), filled-in by surgeons and then monitored by the infection control practitioners.

181,746 procedures were included in our analysis and 3,270 SSIs recorded (global SSI rate 1.8%). The SSI rate decreased significantly from 3.0% in 2003 to 1.1% in 2016. This decrease was mainly in superficial SSIs and high infectious risk procedures. Higher SSI rates were observed for procedures associated with the usual risk factors.