LPS-activated monocytes suppress T-cell immune responses and induce FOXP3+ T cells through a COX-2-PGE2-dependent mechanism

Monocytes initiate innate immune responses and interact with T cells to induce antigen-specific immune responses by antigen presentation and secretion of humoral factors. We have previously shown that adaptive regulatory T cells inhibit T-cell effector functions in a cyclooxygenase (COX)-2-prostaglandin E(2) (PGE(2))-dependent manner and that PGE(2) converts resting CD4+CD25- T cells into FOXP3+ T cells with a suppressive phenotype. Here, we demonstrate that stimulation of monocytes with LPS leads to suppression of T-cell immune responses by a COX-2-PGE(2)-dependent mechanism that is reversible with COX-2 inhibitors as well as PGE(2)-neutralizing antibody and cAMP antagonist. Furthermore, we show that LPS-activated monocytes induce FOXP3 expression in resting CD4+CD25- T cells by the same pathway. These results suggest that monocytes are able to efficiently suppress T-cell immune responses in a regulatory manner and elicit an inhibitory immune profile.     

The Microvascular Anatomy of the Trachea in Adult Xenopus laevis Daudin (Lissamphibia; Anura): Scanning Electron Microscopy of Vascular Corrosion Casts and Correlative Light Microscopy

Studies on the amphibian respiratory tract microvascular anatomy are few and contradictory. Using scanning electron microscopy of vascular corrosion casts, correlative light microscopy of paraplast‐embedded Goldner‐stained serial tissue sections, and three‐dimensional morphometry, we studied the topographic microvascular anatomy in the trachea of the adult South African Clawed Toad, Xenopus laevis Daudin. Histomorphology showed that the cartilaginous portion of the trachea contained irregularly shaped hyaline cartilage plates in its cranial and caudal portions and C‐shaped hyaline cartilage rings in the middle portion. Tracheal cartilages formed large continuous plates on the ventral circumference, numerous small discontinuous plates on the dorsal circumference, and large vertical plates on the caudolateral circumference. The muscular portion of the trachea consisted of bands of smooth muscle that joined the free ends of cartilage plates. The supply of the trachea was via pulmonal artery—tracheobronchial trunk artery—tracheobronchial artery—tracheal artery. The subepithelial capillary network consisted of rectangular meshes which are in the area of the tracheal cartilages located between the cartilages and the respiratory epithelium. Small tracheal veins merged into a single tracheal vein that emptied into the pulmonary vein. Because of its dense subepithelial capillary network and its drainage into the pulmonal vein, the trachea could actively take part in respiration. Anat Rec, 2012. © 2012 Wiley Periodicals, Inc.     

Microglial activation in healthy aging

Healthy brain aging is characterized by neuronal loss and decline of cognitive function. Neuronal loss is closely associated with microglial activation and postmortem studies have indeed suggested that activated microglia may be present in the aging brain. Microglial activation can be quantified in vivo using (R)-[(11)C]PK11195 and positron emission tomography. The purpose of this study was to measure specific binding of (R)-[(11)C]PK11195 in healthy subjects over a wide age range. Thirty-five healthy subjects (age range 19-79 years) were included. In all subjects 60-minute dynamic (R)-[(11)C]PK11195 scans were acquired. Specific binding of (R)-[(11)C]PK11195 was calculated using receptor parametric mapping in combination with supervised cluster analysis to extract the reference tissue input function. Increased binding of (R)-[(11)C]PK11195 with aging was found in frontal lobe, anterior and posterior cingulate cortex, medial inferior temporal lobe, insula, hippocampus, entorhinal cortex, thalamus, parietal and occipital lobes, and cerebellum. This indicates that activated microglia appear in several cortical and subcortical areas during healthy aging, suggesting widespread neuronal loss.     

Poultry raising systems and highly pathogenic avian influenza outbreaks in Thailand: the situation, associations, and impacts

Highly pathogenic avian influenza (HPAI), caused by the virus strain H5N1, currently occurs worldwide with the greatest burden in Southeast Asia where the disease was first reported. In Thailand where the disease was first confirmed in January 2004, the virus had been persistent as a major threat to the poultry industry and human health over the past several years. It was generally hypothesized that the main reason for the disease to circulate in Thailand was the existence of traditional backyard chickens and free-range ducks raising systems. Consequently, this study reviewed the structure of poultry raising systems, the recent outbreaks of HPAI H5N1, the disease association to the backyard and free-grazing poultry production, and consequences of the outbreaks in Thailand. Although the major outbreaks in the country had declined, the sustaining disease surveillance and prevention are still strongly recommended.     

Optimization of supervised cluster analysis for extracting reference tissue input curves in (R)-[(11)C]PK11195 brain PET studies

Performance of two supervised cluster analysis (SVCA) algorithms for extracting reference tissue curves was evaluated to improve quantification of dynamic (R)-[¹¹C]PK11195 brain positron emission tomography (PET) studies. Reference tissues were extracted from images using both a manually defined cerebellum and SVCA algorithms based on either four (SVCA4) or six (SVCA6) kinetic classes. Data from controls, mild cognitive impairment patients, and patients with Alzheimer''s disease were analyzed using various kinetic models including plasma input, the simplified reference tissue model (RPM) and RPM with vascular correction (RPMV_b). In all subject groups, SVCA-based reference tissue curves showed lower blood volume fractions (V_b) and volume of distributions than those based on cerebellum time-activity curve. Probably resulting from the presence of specific signal from the vessel walls that contains in normal condition a significant concentration of the 18 kDa translocation protein. Best contrast between subject groups was seen using SVCA4-based reference tissues as the result of a lower number of kinetic classes and the prior removal of extracerebral tissues. In addition, incorporation of V_b in RPM improved both parametric images and binding potential contrast between groups. Incorporation of V_b within RPM, together with SVCA4, appears to be the method of choice for analyzing cerebral (R)-[¹¹C]PK11195 neurodegeneration studies.     

Evaluation of a cumulative SUV-volume histogram method for parameterizing heterogeneous intratumoural FDG uptake in non-small cell lung cancer PET studies

Purpose  

Standardized uptake values (SUV) are commonly used for quantification of whole-body [¹⁸F]fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) studies. Changes in SUV following therapy, however, only provide a proper measure of response in case of homogeneous FDG uptake in the tumour. The purpose of this study was therefore to implement and characterize a method that enables quantification of heterogeneity in tumour FDG uptake.     

Diversity of lipid-based polyene formulations and their behavior in biological systems

Patients with cancer and infectious diseases often display dyslipidemias that result in changes in their plasma lipoprotein-lipid composition. It is likely that the interactions of liposomal polyenes with plasma lipoproteins may be responsible for the far different pharmacokinetics and pharmacodynamics of these compounds when they are administered to infected patients rather than to animals or healthy volunteers. Amphotericin B (AmpB) and nystatin are examples of such polyenes. Amphotericin B initially distributes with the high-density lipoprotein (HDL) fraction upon incubation in plasma. Over time, AmpB redistributes from HDLs to low-density lipoproteins (LDLs). This redistribution appears to be regulated by lipid transfer protein. However, when AmpB is incorporated into liposomes composed of negatively or positively charged phospholipids, not only is the capability of LTP to transfer AmpB from HDL to LDL diminished, but AmpB remains retained with only the HDL fraction. However, when liposomal nystatin is incubated in plasma, over 50% of nystatin distributes with HDLs. Over time, nystatin redistributes from HDL to the lipoprotein-deficient plasma fraction, which is composed of mainly aqueous plasma proteins. The lipid composition selected for the drug appears to be a vital constituent in regulating the drug's interaction with biological fluids. Furthermore, liposome (or liposomal particle) size, fluidity, and other physiochemical characteristics also play a role in altering the pharmacokinetics and pharmacological effects of lipid-based drug formulations. Armed with this understanding, a rational approach to clinical development of these formulations could be facilitated.     

A Longitudinal Survey for Genome-based Identification of SARS-CoV-2 in Sewage Water in Selected Lockdown Areas of Lahore City,Pakistan: A Potential Approach for Future Smart Lockdown Strategy

In 2019, the newly emerged SARS-CoV-2 virus caused pneumonia-like illness. The disease rapidly spread globally, leading to a worldwide outbreak referred to as the COVID-19 pandemic. The affected patients show symptoms of fever, dry cough, respiratory distress, myalgia, and gastrointestinal disturbance. As of April 5, 2021, 132,083,022 people worldwide were affected by COVID-19, while 2,868,454 people died due to the disease[1]. SARS-CoV-2-positive patients may remain asymptomatic or start showing symptoms in 2?14 days after exposure to the virus[2]. The viral infection can be diagnosed from nasopharyngeal, throat, alveolar lavage, lacrimal, blood, and stool samples. The patient starts shedding the virus in stool regardless of being symptomatic or asymptomatic, which makes sewage-based detection of the virus to be more beneficial in the early infection stage.