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The paper describes the synthesis of an aminopropyl glycoside of hexasaccharide structurally related to the branched fragment of Candida utilis glucomannan, consisting of tetra-α-(1→2)-d-mannoside, the non-reducing end of which is glycosylated with α-glucopyranose and α-mannopyranose residues attached through the (1→2) and (1→3) linkages, respectively. The target structure was assembled by block synthesis with controlled α-stereoselectivity of formation of each glycosidic bond. The resulting hexasaccharide was further converted to a biotinylated conjugate, which, together with previously synthesized similar oligosaccharides, will be used to study the antigenic properties of mannans of Candida fungi. [ABSTRACT FROM AUTHOR]

Introduction: Equine asthma (EA) is a common lower airway disease in horses, but whether its pathogenesis is allergic is ambiguous. Extrinsic stimuli like hay dust induce acute exacerbation of clinical signs and sustained local neutrophilic inflammation in susceptible horses. Aspergillus fumigatus is an EA stimulus, but it is unclear if it merely acts as an IgE-provoking allergen. We aimed to comprehensively analyze immunoglobulin (Ig) isotypes in EA, elucidating their binding to different A. fumigatus antigens, and their quantities systemically in serum and locally in bronchoalveolar lavage fluid (BALF). Methods: Serum and BALF from healthy horses (HE, n = 18) and horses with mildmoderate asthma (MEA, n = 20) or severe asthma (SEA, n = 24) were compared. Ig isotype (IgG1, IgG3/5, IgG4/7, IgG6, IgA, and IgE) binding to nine antigens (A. fumigatus lysate, and recombinant Asp f 1, Asp f 7, Asp f 8, dipeptidylpeptidase 5, class II aldolase/adducin domain protein, glucoamylase, betahexosaminidase, and peptide hydrolase) was compared by enzyme-linked immunosorbent assays. Total Ig isotype contents were determined by beadbased assays. Results: MEA and SEA differed from HE but hardly from each other. Compared to HE, asthmatic horses showed increased anti-A. fumigatus binding of IgG (BALF and serum) and IgA (BALF). Serum and BALF IgE binding and total IgE contents were similar between HE and EA. Single antigens, as well as A. fumigatus lysate, yielded similar Ig binding patterns. Serum and BALF IgG1 binding to all antigens was increased in SEA and to several antigens in MEA. Serum IgG4/7 binding to two antigens was increased in SEA. BALF IgA binding to all antigens was increased in SEA and MEA. Total BALF IgG1 and IgG4/7 contents were increased in SEA, and serum IgG4/7 content was increased in MEA compared to HE. Yet, total isotype contents differentiated EA and HE less clearly than antigen-binding Ig. Discussion: A. fumigatus immunogenicity was confirmed without identification of single dominant antigens here. A. fumigatus provoked elevated BALF IgG1 and IgA binding, and these isotypes appear relevant for neutrophilic EA, which does not support allergy. BALF Ig isotype differentiation beyond IgE is crucial for a comprehensive analysis of immune responses to fungi in EA pathogenesis. [ABSTRACT FROM AUTHOR]

CD39 is the rate-limiting enzyme for the molecular signal cascade leading to the generation of ADP and adenosine monophosphate (AMP). In conjunction with CD73, CD39 converts adenosine triphosphate (ATP) to ADP and AMP, which leads to the accumulation of immunosuppressive adenosine in the tumor microenvironment. This review focuses on the role of CD39 and CD73 in immune response and malignant progression, including the expression of CD39 within the tumor microenvironment and its relationship to immune effector cells, and its role in antigen presentation. The role of CD39- and CD73-targeting therapeutics and cancer-directed clinical trials investigating CD39 modulation are also explored. Executive summary Enzyme structure CD39 is an integral membrane protein that dephosphorylates adenosine triphosphate (ATP) to adenosine monophosphate (AMP) and CD73 further dephosphorylates AMP to adenosine (ADO). These enzymes are expressed on different cell types within the tumor microenvironment. Tumor microenvironment Tumor activity and host immune response hinge on the delicate balance between ATP and ADO accumulation within the tumor microenvironment and include the activation of receptors such as A2A and P2X7. CD39 as a biomarker CD39 expression has been identified as a clinically significant positive predictor of ovarian cancer response to immunotherapy. CD39 & CD73 inhibitor trials Anti-CD39 and anti-CD73 monoclonal antibodies are currently being investigated in clinical trials as monotherapies and in combination, with many underway. Oleclumab, an anti-CD73 monoclonal antibody, has recently been shown to be effective with a tolerable safety profile in treating non-small-cell lung cancer with EGFR mutation and will be moving to phase II (NCT03381274). [ABSTRACT FROM AUTHOR]

Cryptococcosis is a global invasive mycosis associated with significant morbidity and mortality. Cryptococcal antigen (CrAg) testing from serum and cerebrospinal fluid (CSF) has been regarded as a gold standard for early diagnosis. This study aimed to develop and validate a rapid and sensitive sandwich chemiluminescent magnetic microparticle immunoassay (CMIA) for quantitative detection of CrAg in sera. CMIA is based on magnetic beads modified with capture antibodies and biotinylated antibodies and Streptavidin-polyHRP, where biotinylated antibodies functioned as the recognition element and Streptavidin-polyHRP as the signal component. Assay parameters were first optimized, and then assay performances were evaluated. Under optimized conditions, the total runtime of the CMIA was 22 min. The assay had a wide linear range (2 –10,000 ng/mL) and high analytical sensitivity (0.24 ng/mL), together with acceptable reproducibility, accuracy, and stability. Besides, it exhibited no cross-reactivity with other pathogens. Importantly, the assay showed 92.91% (95% CI, 80.97–93.02%) overall qualitative agreement with a commercial ELISA kit in a retrospective cohort of 55 cases with confirmed cryptococcal infection, and 72 controls without evidence of invasive fungal disease (IFD). These results demonstrated that the present study paved a novel strategy for reliable quantitative detection of CrAg in sera. [ABSTRACT FROM AUTHOR]

Objective: Although human blood consists of the same basic parts (red blood cells, white blood cells, platelets, and plasma), there are a large variety of blood groups and types, each with its own different characteristics. The aim of this study to search the correlation between different types of blood groups and increase risk factor for type 2 diabetic mellitus disease. Methods: Blood is made up of several components, and all of these can be utilized to management a lot of different illness. What makes a blood type different is the combination of protein molecules called antigens and antibodies. A person's blood type is also considered to be inherited from the parents' genes. Diabetic mellitus type 2 is related with a type of a chronic illness that effect the trend of the cells in the body for receive glucose or the amount of insulin which synthesize in the pancreas, thus leads to an abnormal decrease or increase in the scale of glucose in the blood. Results: Blood type O had a low risk of diabetes for women with type A, and same for women with type A. Group AB, and low persent of type B, compared with blood group O, have poor chances of developing diabetes. Conclusions: The effect of blood types should be investigated in future clinical and epidemiological studies on diabetes, also there is a need for more research on the pathophysiological mechanism to explain why diabetes has people of group O have a low risk of developing type 2 diabetes. [ABSTRACT FROM AUTHOR]

Background: CA 19-9 is a commonly assessed tumor marker, considered characteristic of pancreatic ductal adenocarcinoma (PDAC) and biliary tract cancers; however, the positive predictive value of CA 19.9 is too low, and the usage of CA 19.9 as a screening tool in the healthy population remains controversial. Methods: The presented case illustrates a reversed diagnosis of highly elevated serum CA 19-9 levels in a 54-year-old female complaining of pain in the epigastric region, shortly after COVID-19 vaccination. Laboratory tests showed a significantly elevated level of the CA 19-9 marker (>12,000 U/mL, reference value: <37 U/mL) with normal pancreatic enzyme activity. The patient underwent imaging examination, which showed no abnormalities, except for increased pancreatic dimension and areas of fluid signal in the pancreas in magnetic resonance imaging (MRI), which may correspond to autoimmune pancreatitis (AIP). The patient remains asymptomatic with a recommendation for a follow-up MRI in 12 months. Results: A literature review conducted revealed multi-causal CA 19-9 increases above 1000 U/mL, including non-cancerous diseases of the lung, pancreas, liver, ovary, kidney, and others. The median concentration of CA 19-9 regardless of the cause of disease was 2810 U/mL (IQR ± 6895). The median CA 19-9 values in men and women were 3500 (IQR ± 10,050) and 2455 (IQR ± 3927), respectively, and differ significantly between the compared groups (p < 0.05). There was no difference between CA 19-9 values and the categorized cause of the increase. Conclusions: Conducting differential diagnosis, it should not be forgotten that most international guidelines recommend the use of CA 19-9 only in conjunction with pathology of pancreas in radiological imaging; however, even such a combination can point the diagnostic pathway in the wrong direction. A highly elevated CA 19-9 level, typically associated with PDAC, may be the result of benign disease including AIP related to COVID-19 vaccination. [ABSTRACT FROM AUTHOR]

Nanoparticles have been identified in numerous studies as effective antigen delivery systems that enhance immune responses. However, it remains unclear whether this enhancement is a result of increased antigen uptake when carried by nanoparticles or the adjuvanticity of the nanoparticle carriers. Consequently, it is important to quantify antigen uptake by dendritic cells in a manner that is free from artifacts in order to analyze the immune response when antigens are carried by nanoparticles. In this study, we demonstrated several scenarios (antigens on nanoparticles or inside cells) that are likely to contribute to the generation of artifacts in conventional fluorescence-based quantification. Furthermore, we developed the necessary assay for accurate uptake quantification. PLGA NPs were selected as the model carrier system to deliver EsxB protein (a Staphylococcus aureus antigen) in order to testify to the feasibility of the established method. The results showed that for the same antigen uptake amount, the antigen delivered by PLGA nanoparticles could elicit 3.6 times IL-2 secretion (representative of cellular immune response activation) and 1.5 times IL-12 secretion (representative of DC maturation level) compared with pure antigen feeding. The findings above give direct evidence of the extra adjuvanticity of PLGA nanoparticles, except for their delivery functions. The developed methodology allows for the evaluation of immune cell responses on an antigen uptake basis, thus providing a better understanding of the origin of the adjuvanticity of nanoparticle carriers. Ultimately, this research provides general guidelines for the formulation of nano-vaccines. [ABSTRACT FROM AUTHOR]