Dempseyfulton1343
This was confirmed by IHC. In HT-29 cells, tunicamycin-induced ER stress triggered AGR2 intracellular expression and its secretion. Supernatant of these HT-29 cells, pre-conditioned by tunicamycin, led to a myofibroblastic differentiation when applied on CCD-18Co fibroblasts. By using recombinant protein and blocking agent for AGR2, we demonstrated that the secretion of this protein by epithelial cells can play a role in the myofibroblastic differentiation.
The development of CD fibrotic strictures could involve epithelial ER stress and particularly the secretion of AGR2.
The development of CD fibrotic strictures could involve epithelial ER stress and particularly the secretion of AGR2.Evidence indicates that macrophages play an important role in the immune system. Therefore, research involving inflammatory and oxidative stress responses in macrophages is of great significance. Many factors contribute to inflammation and oxidative stress, including Salmonella. We investigated the effect of the miR-139-5p/TRAF6 axis on the inflammatory and oxidative stress responses of Salmonella -infected macrophages. Our findings revealed that miR-139-5p decreased IL-1β and TNF-α levels to inhibit Salmonella-induced inflammatory responses in the RAW264.7 macrophage cell line. Furthermore, miR-139-5p inhibited Salmonella-induced oxidative stress by strengthening SOD, CAT and GSH-PX activity, as well as lowering the malondialdehyde level in the RAW264.7 macrophages cell line. Subsequently, it was verified that TRAF6 was a downstream target of miR-139-5p in RAW264.7 cells. Rescue assays indicated that the over-expression of miR-139-5p inhibits the effects of TRAF6 on inflammatory and oxidative stress responses including Salmonella infection in RAW264.7 cells. To our knowledge, this study is the first to verify that miR-139-5p inhibits inflammatory and oxidative stress responses of Salmonella-infected macrophages through regulating TRAF6. This discovery may offer new insights on inflammatory and oxidative stress responses in macrophages.
CYD-TDV, a live, attenuated, tetravalent dengue vaccine, has been approved for the prevention of symptomatic dengue in previously dengue exposed individuals. This post-hoc analysis assessed hospitalized and severe virologically-confirmed dengue (VCD) over the complete 6-year follow-up of three CYD-TDV efficacy studies (CYD14, CYD15 and CYD23/CYD57).
The main outcomes were hazard ratios (HRs) for hospitalized or severe VCD by baseline dengue serostatus, focusing on those who were seropositive, and by age at immunization (<9 years/≥9 years). Baseline dengue serostatus was measured or inferred using several methods. Hospitalized VCD cases were characterized in terms of clinical signs and symptoms and wild-type viremia level. WZ811 Antibody persistence was assessed up to five years after the last injection.
In those aged ≥9 years and baseline seropositive, CYD-TDV protected against hospitalized and severe VCD over six years compared to placebo (HR [95% confidence interval] Multiple Imputation from Month 0 method, 0.19 [0.12-0.30] and 0.15 [0.06-0.39]; other methods were consistent). Vaccine protection was observed over the different study periods, being highest during the first 2 years. Evidence for a decreased risk of hospitalized and severe VCD was also observed in seropositive participants aged 6-8 years. Clinical signs and symptoms, and quantified dengue viremia from participants with hospitalized VCD were comparable between groups.
CYD-TDV demonstrated robust protection against hospitalized and severe VCD over the entire six-year follow-up in participants who were seropositive and ≥9 years old. Protection was also observed in seropositive 6-8 year olds.
CYD-TDV demonstrated robust protection against hospitalized and severe VCD over the entire six-year follow-up in participants who were seropositive and ≥9 years old. Protection was also observed in seropositive 6-8 year olds.Maternal and cord blood sera were collected from 20 parturients who received the BNT162b2 vaccine. All women and infants were positive for anti S- and anti-RBD-specific IgG. Cord blood antibody concentrations were correlated to maternal levels and to time since vaccination. Antenatal SARS-CoV-2 vaccination may provide maternal and neonatal protection.Clinical trials indicate that sodium/glucose co-transporter 2 (SGLT2) inhibitors (SGLT2i) improve kidney function, yet, the molecular regulation of SGLT2 expression is incompletely understood. Here, we investigated the role of the intrarenal renin-angiotensin system (RAS) on SGLT2 expression. In adult non-diabetic participants in the Nephrotic Syndrome Study Network (NEPTUNE, n=163), multivariable linear regression analysis showed SGLT2 mRNA was significantly associated with angiotensinogen (AGT), renin, and angiotensin-converting enzyme (ACE) mRNA levels (P less then 0.001). In vitro, angiotensin II (Ang II) dose-dependently stimulated SGLT2 expression in HK-2, human immortalized renal proximal tubular cells (RPTCs); losartan and antioxidants inhibited it. Sglt2 expression was increased in transgenic (Tg) mice specifically overexpressing Agt in their RPTCs, as well as in WT mice with a single subcutaneous injection of Ang II (1.44 mg/kg). Moreover, Ang II (1000 ng/kg/min) infusion via osmotic mini-pump in WT mice for 4 weeks increased systolic blood pressure (SBP), glomerulosclerosis, tubulointerstitial fibrosis, and albuminuria; canaglifozin (Cana, 15 mg/kg/day) reversed these changes, with the exception of SBP. Fractional glucose excretion (FeGlu) was higher in Ang II+Cana than WT+Cana, whereas Sglt2 expression was similar. Our data demonstrate a link between intrarenal RAS and SGLT2 expression and that SGLT2i ameliorates Ang II-induced renal injury independent of SBP.
The etiology and optimal clinical management of acute febrile illness (AFI) is poorly understood.
Blood samples taken from study participants with acute fever (≥37.5°C) or a history of fever and recruited into the previous Typhoid-Fever-Surveillance-in-Africa (TSAP) study were evaluated using a polymerase chain reaction (PCR)-based TaqMan-Array Card designed to detect a panel of bacterial, viral and parasitic pathogens. Clinical metadata were also assessed.
A total of 615 blood samples available for analysis originated from Burkina Faso (n=53), Madagascar (n=364) and Sudan (n=198) and were taken from participants ranging from 0-19 years of age. Most individuals [86.4% (531/615)] presenting at healthcare facilities were outpatient adolescents (11-19 years-old). Leading clinical diagnoses were respiratory tract infections [45.9% (282/615)], malaria [27.3% (168/615)], and gastrointestinal tract infections [10.7% (66/615)]. Through the TaqMan-Array Card, at least one pathogen was detected in 62% (33/53), 24es and carries implications for the appropriate management of this common syndrome.
Following the 2013-2016 West African Ebola outbreak, distinct, persistent health complaints were recognized in Ebola virus disease (EVD) survivors. Here we provide an in-depth characterization of post-Ebola syndrome over 2.5 years after resolution of disease. Additionally, we report sub-phenotypes of post-Ebola syndrome with overlapping symptom clusters in survivors from Eastern Sierra Leone.
Participants in Eastern Sierra Leone were identified by the Sierra Leone Association of Ebola survivors. Survivors and their contacts were administered a questionnaire assessing self-reported symptoms and a physical exam. Comparisons between survivors and contacts were conducted using conditional logistic regression. Symptom groupings were identified using hierarchical clustering approaches. Simplified Presentation of Incredibly Complex Evaluations (SPICE), correlation analysis, logistic regression and principal component analysis (PCA) were performed to explore the relationships between symptom clusters.
375 EVD snts an in-depth characterization of post-Ebola syndrome in Sierra Leonean survivors over 2.5 years after disease. The interrelationship between symptom clusters indicates that post-Ebola syndrome is a heterogeneous disease. The distinct musculoskeletal and non-musculoskeletal phenotypes identified likely require targeted therapies to optimize long-term treatment for EVD survivors.Whether increased natural enemy density or adding a second natural enemy species will provide superior pest suppression in greenhouse augmentative biological control is unknown for many commercially available natural enemy species. In this study, we use sweetpotato whiteflies, Bemisia tabaci (Gennadius) (Hemiptera Aleyrodidae), on poinsettias, Euphorbia pulcherrima Willd. ex Klotzsch (Malpighiales Euphorbiaceae), to determine whether adding Amblyseius swirskii (Athias-Henriot) (Acari Phytoseiidae) to Eretmocerus eremicus Rose and Zolnerowich (Hymenoptera Aphelinidae) is better for B. tabaci suppression compared with either natural enemy alone, both with and without challenges with whitefly immigration or delayed natural enemy releases. The number of whiteflies on caged poinsettias treated with different natural enemy release rates (single or double rate), natural enemy species (one or two species), natural enemy delayed release (weeks 4 and 8), and whitefly immigration treatments (introduced at week 4 or week 8) was censused biweekly for 16 wk. Both species used in combination provided similar or better suppression of whiteflies compared with either natural enemy alone. Both species combined also provided superior suppression of whiteflies when challenged with whitefly immigration or delays in natural enemy releases compared with E. eremicus alone. Whitefly immigration or delays in E. eremicus releases did not increase whitefly populations, suggesting that suppression of whiteflies by E. eremicus alone is relatively robust. This study found no evidence for negative interactions between E. eremicus and A. swirskii for suppressing B. tabaci.The hallmark of Lafora disease, a fatal neurodegenerative disorder, is the accumulation of intracellular glycogen aggregates, called Lafora bodies. Until recently, it was widely believed that brain Lafora bodies were present exclusively in neurons and thus that Lafora disease pathology derived from their accumulation in this cell population. However, recent evidence indicates that Lafora bodies are also present in astrocytes. To define the role of astrocytic Lafora bodies in Lafora disease pathology, we deleted glycogen synthase specifically from astrocytes in a mouse model of the disease (malinKO). Strikingly, blocking glycogen synthesis in astrocytes-thus impeding Lafora bodies accumulation in this cell type-prevented the increase in neurodegeneration markers, autophagy impairment, and metabolic changes characteristic of the malinKO model. Conversely, mice that overaccumulate glycogen in astrocytes showed an increase in these markers. These results unveil the deleterious consequences of the deregulation of glycogen metabolism in astrocytes and change the perspective that Lafora disease is caused solely by alterations in neurons.
Indoor environments are considered one of the main settings for transmission of SARS-CoV-2. Households in particular represent a close-contact environment with high probability of transmission between persons of different ages and with different roles in society.
Complete households with a laboratory-confirmed SARS-CoV-2 positive case in the Netherlands (March-May 2020) were included. At least three home visits were performed during 4-6 week of follow-up, collecting naso- and oropharyngeal swabs, oral fluid, feces and blood samples for molecular and serological analyses of all household members. Symptoms were recorded from two weeks before the first visit through to the final visit. Infection secondary attack rates (SAR) were estimated with logistic regression. A transmission model was used to assess transmission routes in the household.
A total of 55 households with 187 household contacts were included. In 17 households no transmission took place, and in 11 households all persons were infected. Estimated infection SARs were high, ranging from 35% (95%CI 24%-46%) in children to 51% (95%CI 39%-63%) in adults.
