Compartmentalization and Interaction of Pax5 and Pax6 in Brain of Mice

Many transcription factors play important roles to maintain the microenvironment, integrity of the blood-brain barrier, the neurons-glia interaction, activities of microglia, composition of cerebrospinal fluid, metabolic activities, concentration of neurotransmitters, presence of inflammatory and anti-inflammatory cytokines, ischemia, stress, aging, neurological disorders, and diseases. The Paired box transcription factors and multifunctional proteins, Pax6 and Pax5 are expressed in brain. They regulate several regulators from cell cycle to cell death. The Pax5, a B-cell lineage-specific activator protein (BSAP), is expressed in the cerebellum, cerebral cortex, hippocampus, olfactory bulb, third ventricles, and choroid plexus. The Pax5 has been observed down-regulated in autism, mental retardation, and Glioblastoma multiforme. The Pax6 affects genes of neurodegeneration, immunological surveillance, and energy homeostasis in brain of mice. The Pax5 and Pax6 recognize several similar DNA sequences and regulate the expression of genes in a tissue-specific manner. Therefore, it is presumed that Pax5 and Pax6, are compartmentalized in brain of mice. Results indicate interactions, cell and tissue-specific compartmentalization, and co-localization of Pax5 and Pax6 in the cerebral cortex, cerebellum, and hippocampus in brain of mice.

Integrated Analysis of Helicobacter Pylori-Related Prognostic Gene Modification Patterns in the Tumour Microenvironment of Gastric Cancer

Background Helicobacter pylori (HP) infection is one of the leading causes of gastric cancer (GC). However, the interaction between HP and the TME, and its carcinogenic mechanism remains unknown. Methods We screened 28 HP-related prognostic genes based on HP infection-related gene markers and HP infection sample datasets (GSE6143 and GSE60662). We then constructed an HPscore system by using the principal component analysis algorithm and successfully quantified the HP modification characteristics of a single GC sample. In addition, we comprehensively analysed the relationship between the HPscore and the clinical characteristics of patients with GC, the immune cell infiltration characteristics of the TME and stemness. Results We successfully identified 28 HP-related prognostic genes that accurately classified the GC population. There are significant differences in survival between different subgroups(high-, low-risk and cluster_1,2). Thereafter, we constructed the HPscore system to systematically evaluate the modification characteristics of the 28 HP-related prognostic genes, and the internal and external validation of the HPscore system suggested similar results: the overall survival rate in the high -HPscore group was poor, and immunological surveillance was reduced, whereas the low-HPscore group had a survival advantage, and was related to the inflammatory response. HPscore was also strongly correlated with the tumour stage, TME cell infiltration and stemness. Conclusions HP-modified characteristics play a crucial role in the TME and tumourigenesis. HPscore evaluation of a single tumour sample can help identify the TME characteristics and the carcinogenic mechanism of GC patients infected with HP, based on which personalised treatment can be administered.

Genotype-specific Features Reduce the Susceptibility of South American Yellow Fever Virus Strains to Vaccine-Induced Antibodies

The resurgence of yellow fever in South America has prompted mitigation through vaccination against the etiologic agent, yellow fever virus (YFV). Current vaccines are based on a virulent African isolate, and their capacity to induce neutralizing antibodies against the vaccine strain is widely used as a surrogate for protection. However, the sensitivity of genetically distinct South American strains to vaccine-induced antibodies is unknown. Here, we show that antiviral potency of the polyclonal antibody response in both U.S. and Brazilian vaccinees is attenuated against an emergent Brazilian strain. This reduction was attributable to genetic changes at two sites in the central domain II of the glycoprotein E, including the acquisition of an N linked glycosylation site, which are unique to and shared among most South American YFV strains. Our findings call for a reevaluation of current approaches to YFV immunological surveillance in South America and suggest approaches for designing updated vaccines.

Serological Testing for COVID-19, Immunological Surveillance, and Exploration of Protective Antibodies

Serological testing is a powerful tool in epidemiological studies for understanding viral circulation and assessing the effectiveness of virus control measures, as is the case of SARS-CoV-2, the pathogenic agent of COVID-19. Immunoassays can quantitatively reveal the concentration of antiviral antibodies. The assessment of antiviral antibody titers may provide information on virus exposure, and changes in IgG levels are also indicative of a reduction in viral circulation. In this work, we describe a serological study for the evaluation of antiviral IgG and IgM antibodies and their correlation with antiviral activity. The serological assay for IgG detection used two SARS-CoV-2 proteins as antigens, the nucleocapsid N protein and the 3CL protease. Cross-reactivity tests in animals have shown high selectivity for detection of antiviral antibodies, using both the N and 3CL antigens. Using samples of human serum from individuals previously diagnosed by PCR for COVID-19, we observed high sensitivity of the ELISA assay. Serological results with human samples also suggest that the combination of higher titers of antiviral IgG antibodies to different antigen targets may be associated with greater neutralization activity, which can be enhanced in the presence of antiviral IgM antibodies

Thymic Carcinomas and Second Malignancies: A Single-Center Review

Thymic carcinomas account for less than 0.01% of new cancer diagnoses annually and are more aggressive than thymomas. Autoimmune disorders have been associated with thymomas and only recently with thymic carcinomas. Second malignancies are well described after thymomas. The aim of this study was to analyze the incidence of second malignancies in patients with thymic carcinomas. All cases of thymic carcinomas were identified from the pathology archives of Indiana University. Histological materials were reviewed and further correlated with clinical data to identify incidence of second cancers in patients with thymic carcinomas. Histological material was available for review in 92 cases of thymic carcinoma. Clinical data were available for 85 patients. Fourteen of these (16.5%) patients had a second malignancy; these included small cell lung carcinoma, “testicular cancer”, embryonal carcinoma, seminoma, breast carcinoma (two cases), prostatic adenocarcinoma, Hodgkin’s lymphoma, thyroid carcinoma, bladder carcinoma (two cases), renal cell carcinoma, and melanoma. The latter could precede, be concurrent with, or follow the diagnosis thymic carcinoma. The incidence of second cancers in patients with thymic carcinomas is similar to that reported for thymomas. Abnormalities in immunological surveillance may be responsible for this high incidence of second malignancies in thymic tumors.

Loss of p16: A Bouncer of the Immunological Surveillance?

p16INK4A (hereafter called p16) is an important tumor suppressor protein frequently suppressed in human cancer and highly upregulated in many types of senescence. Although its role as a cell cycle regulator is very well delineated, little is known about its other non-cell cycle-related roles. Importantly, recent correlative studies suggest that p16 may be a regulator of tissue immunological surveillance through the transcriptional regulation of different chemokines, interleukins and other factors secreted as part of the senescence-associated secretory phenotype (SASP). Here, we summarize the current evidence supporting the hypothesis that p16 is a regulator of tumor immunity.

Decrease of peripheral blood mucosal‐associated invariant T cells and impaired serum Granzyme-B production in patients with gastric cancer

Mucosal-associated invariant T (MAIT) cells are an invariant T cell subset, which have been reported to play an antimicrobial role in infectious diseases. However, little is known about it in malignant diseases and tumors, especially in gastric cancer (GC). So in this study, we aim to examine the frequency, phenotype, partial functional capacity and clinical relevance of this cells from GC patients’ peripheral blood by flow cytometry. It was shown that the frequency of peripheral blood MAIT cells was negatively correlated with their increasing age in healthy adults. Importantly, comparing to the healthy controls (HC), the frequency and the absolute number of MAIT cells from GC patients’ peripheral blood with or without chemotherapy were both significantly lower than those. For the phenotype, the proportion of CD4−MAIT cell subset in GC patients without chemotherapy was lower than in HC, but higher than in GC patients with chemotherapy. Whereas, the proportion of CD4−CD8+MAIT cell subset in GC patients without chemotherapy was significantly lower than that in HC. Finally, the level of Granzyme-B (GrB), a molecule associated with MAIT cells was markedly lower in GC patients. But the correlation between the serum levels of GC-associated tumor antigens and the percentages of MAIT cells in GC patients was not observed. In conclusion, our study shows the decreased frequency, changed phenotypes and partial potentially impaired function of MAIT cells in GC patients, suggesting a possible MAIT cell-based immunological surveillance of GC.