MXD3 as an Immunological and Prognostic Factor From Pancancer Analysis

MAX dimerization protein 3 (MXD3), a transcriptional regulator of the MXD3 superfamily, is a part of the MYC–MAX–MXD network. However, its role in tumors has been reported in several cancers, such as B-cell acute lymphoblastic leukemia, medulloblastoma, neuroblastoma, and glioblastoma. Based on TCGA and GEO data, our first pancancer study of MXD3 confirmed the high expression of MXD3 in cancer tissues. Our results revealed that patients suffering from cancers with higher MXD3 expression had poor OS, DSS, DFI, and PFI. We further explored the methylation status of the MXD3 gene body and gene promoter in cancer. Patients with a higher MXD3 gene body have better OS, while the prognosis of patients with a high MXD3 promoter is more complex. We also verified the differential expression of three clinical phenotypes of MXD3: age, sex, and tumor stage, in a variety of tumors, suggesting a correlation between MXD3 and clinical characteristics. We explored the negative relationship between MXD3 and TMB and MSI in most types of cancer, indicating the poor prognosis of patients with high MXD3 expression. We further investigated the relationship between MXD3 and immune infiltrating cells and identified the relationship between MXD3 and immune genes, immunosuppressive genes, and antigen-presenting genes. All of the above findings established a solid relationship between MXD3 and the immune environment and immune cells. These results demonstrated that MXD3 might also be a potential immune factor. We also found a higher expression of MXD3 and promoter according to the increasing glioma WHO grade or histologic types. Glioma patients with high MXD3 or MXD3 promoter expression had poor survival. Finally, we used IHC to verify the higher expression of MXD3 in glioma samples compared to normal samples. Our study shows that MXD3, as a poor prognostic factor, plays a significant role in many cancers, especially glioma. Although more clinical evidence for MXD3 as a clinical therapeutic target and an immunotherapy site is needed, MXD3 can play an important guiding role in multiple clinical treatments, including immunotherapy and demethylation therapy.

Investigation on the Correlation between Serum Immune Factor Levels and Allergic Constitution in Children with Infectious Mononucleosis

Objective. To investigate the correlation between serum immune factor levels and allergic constitution in children with infectious mononucleosis. Methods. A total of 120 children who visited our hospital from March, 2019, to December, 2020, were selected as the research objects, and 40 children who came to our hospital for physical examination were included in the control group (CG). 40 children with IM were classified into the IM group (IG), and 40 IM children with allergic rhinitis, allergic dermatitis, asthma, and other allergic diseases were classified into the IM allergy group (AG). On the second day of admission, 5 ml of fasting venous blood was collected from all children in the early morning to observe the serum IgE level, the level of lymphocyte subsets, and the level of immunoglobulin of the patient. Results. The serum CD3, CD4, and CD8 levels of children in AG were significantly higher than those in IG and CG ( P < 0.05 ). The serum IgE, IgA, IgM, and IgG levels of children in AG were significantly higher than those of IG and CG ( P < 0.05 ). The serum IgE levels of children in AG were positively correlated with the serum CD3, CD4, and CD8 levels ( P < 0.05 ). There was a positive correlation between the serum IgE level and serum IgA, IgM, and IgG levels in children with AG ( P < 0.05 ). Conclusion. The results of this study showed that there may be a certain relationship between allergic constitution and the incidence, clinical manifestations, and prognosis of infectious mononucleosis. IgE level can be used as a reference index for the early severity of IM clinical symptoms.

Platelet Refractoriness Evaluation after Platelet Concentrate Transfusion in Pediatric Leukemia

Platelet transfusion is being used in 67%-75% of hematology malignancies including leukemia. Platelet refractoriness is the failure to achieve satisfactory responses to platelet transfusions. Many transfusion centres use 1 hour and 24 hours after transfusion Corrected Count Increment (CCI) value to define platelet refractoriness. To analyze platelet refractory based on CCI-1h and CCI-24h value after Platelet Concentrate (PC) tranfusion in pediatric leukemia and the effect of non immune factors on platelet refractoriness. Subjects were evaluated for platelet count after 10-120 minutes and 18-24 hours of PC tranfusion to calculate CCI-1h and CCI-24h. Platelet Refractoriness was defined when CCI-1h <5×109/L and CCI-24h <4.5×109/L. Each subject was observed for non-immune platelet refractory factors. Interestingly, from 25 PC transfusion there was 20% platelet refractoriness of CCI-1h and 40% of CCI-24h. There was a significant difference CCI-1h and CCI-24h (p=0.027). Non immune factor had no effect for platelet refractoriness. Platelet count should be analyzed after 24 hours PC transfusion to diagnose platelet refractoriness. Further research including immune factor examination is needed.

Effects of Coated Cysteamine on Oxidative Stress and Inflammation in Weaned Pigs

This study aimed to explore the effects of dietary coated cysteamine on oxidative stress and inflammation in diquat-induced weaning pigs. Twenty-four pigs were randomly assigned to three dietary groups with eight replicates: the control (fed base diet), diquat (fed base diet), and coated cysteamine + diquat groups (fed 80 mg/kg cysteamine). The experiment was conducted for 21 d, and consisted of a pre-starter period (14 d) and a starter period (7 d). Coated cysteamine treatment significantly increased (p < 0.05) the final weight and average daily gain (ADG) in pigs. The contents of alkaline phosphatase (ALP), immunoglobulin G (IgG), serine (Ser), and isoleucine (Ile) were elevated (p < 0.05) while the contents of albumin (ALB) and aspartic acid (Asp) were reduced (p < 0.05) in the serum after coated cysteamine supplementation. Coated cysteamine supplementation resulted in greater (p < 0.05) serum superoxide dismutase (SOD) activity, the expression of interleukin-10 (IL-10) mRNA in the colon, and the CuSOD mRNA expression in the jejunum (p < 0.05) and colon (p = 0.073). Coated cysteamine supplementation showed an increasing trend in villus height (p = 0.060), villus height/crypt depth (V/C) (p = 0.056), the expression levels of zonula occludens-1 (ZO-1) mRNA (p = 0.061), and Occludin mRNA (p = 0.074) in the jejunum. In summary, dietary supplementation with coated cysteamine improves the intestinal barrier function of the jejunum by increasing the immunoglobulin content and the relative expression of intestinal immune factor mRNA in pigs while alleviating oxidative stress and inflammatory reactions caused by diquat.

Effects of Inflammation on the Immune Microenvironment in Gastric Cancer

BackgroundChronic inflammation and immune cell dysfunction in the tumor microenvironment are key factors in the development and progression of gastric tumors. However, inflammation-related genes associated with gastric cancer prognosis and their relationship with the expression of immune genes are not fully understood.MethodIn this study, we established an inflammatory response model score called “Riskscore”, based on differentially expressed genes in gastric cancer. We used Survival and Survminer packages in R to analyze patient survival and prognosis in risk groups. The survival curve was plotted using the Kaplan–Meier method, and the log-rank test was used to assess statistical significance, and we performed the ROC analysis using the R language package to analyze the 1-, 3-, and 5-year survival of patients in the GEO and TCGA databases. Single-factor and multi-factor prognostic analyses were carried out for age, sex, T, N, M, and risk score. Pathway enrichment analysis indicated immune factor-related pathway enrichment in both patient groups. Next, we screened for important genes that are involved in immune cell regulation. Finally, we created a correlation curve to explore the correlation between Riskscore and the expression of these genes.ResultsThe prognosis was significantly different between high- and low-risk groups, and the survival rate and survival time of the high-risk group were lower than those of the low-risk group. we found that the pathways related to apoptosis, hypoxia, and immunity were most enriched in the risk groups. we found two common tumor-infiltrating immune cell types (i.e., follicular helper T cells and resting dendritic cells) between the two risk groups and identified 10 genes that regulate these cells. Additionally, we found that these 10 genes are positively associated with the two risk groups.ConclusionFinally, a risk model of the inflammatory response in gastric cancer was established, and the inflammation-related genes used to construct the model were found to be directly related to immune infiltration. This model can improve the gastric cancer prognosis prediction. Our findings contribute to the development of immunotherapy for the treatment of gastric cancer patients.

A Novel Vaccine RNA-peptide against HIV-1: Exosomes as Carrier in Viral Progression

Introduction of a new drug/vaccine model against HIV-1 with prophylactic and therapeutic actions, also useful, in HIV-1 rehabilitation. This RNA-peptide vaccine projects involving RNA from SARS-CoV-2, and peptides from human HIV-1 and human PARP-1 proteins. As mRNA target, we used primers miRNA repertoire and host immune factor regulation upon avian coronavirus infection in eggs. The primers were modified with poly adenine (A) target. We designed the peptides target from HIV-1 protein and PARP-1 human protein. Our analysis, according to the algorithms Cruz Rodriguez (CR) identified an RNA-peptide with theorical fusion value stability FS=80.04 cruz, EA= 97.22 ro and BA= 1.21 to treat HIV-1. Where, we are proposing, the exosomes and how these vesicles could function as carriers of our RNA-peptide molecule. In this study, we expect that major histocompatibility complex l (MHC l) bind the molecule peptide (B) generated by hydrolysis (DEVD) of molecule RNA-peptide (AB) after induction of apoptosis pathways by caspase 3 or caspase 7. Also, we expect that major histocompatibility complex ll (MHC ll) bind the molecule RNA-peptide (A) generated and recognition by appropriate T-cells at the infected cell with HIV-1.

Towards the NMR solution Structure and the Dynamics of the C-terminal Region of APOL1 and its G1, G2 Variants with a Membrane Mimetic

Secreted apolipoprotein L1 (APOL1) is well known as an innate immune factor, protecting against African trypanosomiasis. The intracellular form has multiple functions, including regulating autophagy, intracellular vesicle trafficking, and ion channel activity. The APOL1 protein (G0) has two common variants (denoted G1 and G2) in the C-terminal region and are associated with a high risk of chronic kidney disease (CKD) and progression to end-stage kidney disease. Our previous studies using molecular modeling suggested that APOL1 G1 and G2 stabilize an autoinhibited state of the C-terminus, leading to impaired intracellular interactions with SNARE proteins. To characterize the structural consequence of kidney disease-associated APOL1 variants further, we assigned the C-terminal region proteins using 1H, 13C, 15N multidimensional nuclear magnetic resonance (NMR) spectra in solution in the presence of membrane mimetic dodecylphosphocholine micelles. We then derived models for the three-dimensional structure of APOL1-G0, and -G1 and -G2 variant C-terminal regions using the chemical shifts of the main chain nuclei followed by NMR relaxation measurements. The data suggest that changes in the three-dimensional structure of APOL1 C-terminal region induced by kidney disease-associated variants, not least the alteration of key sidechains and their interactions, could disrupt membrane association and the yet to be characterized protein-protein interactions including its binding partners, such as SNARE proteins. Such interactions could underlie the intracellular mechanisms that mediate the pathogenesis of CKD. In the future, one may try to reverse such structural and dynamics changes in the protein by designing agents that may bind and then mitigate APOL1 variant-associated CKD.