Control of MHC class I traffic from the endoplasmic reticulum by cellular chaperones and viral anti-chaperones

MHC class I molecules assemble with peptides in the endoplasmic reticulum (ER). To ensure that only peptide-loaded MHC molecules leave the ER, empty molecules are retained by ER-resident chaperones, most notably the MHC-specific tapasin. ER exit of class I MHC is also controlled by viruses, but for the opposite purpose of preventing peptide presentation to T cells. Interestingly, some viral proteins are able to retain MHC class I molecules in the ER despite being transported. By contrast, other viral proteins exit the ER only upon binding to class I MHC, thereby rerouting newly synthesized class I molecules to intracellular sites of proteolysis. Thus, immune escape can be achieved by reversing, inhibiting or redirecting the chaperone-assisted MHC class I folding, assembly and intracellular transport.     

Bacterial DNA as immune cell activator

Pattern recognition receptors of the innate and adaptive immune systems apparently recognize unmethylated CpG motifs of bacterial DNA. Cells of the innate immune system are activated directly by CpG motifs, and the resulting response dictates a Th1 bias to the developing adaptive immune response. Interestingly, antigen receptor occupancy of cells of the adaptive immune system augments their responsiveness to CpG motifs, suggesting that co-stimulatory mechanisms are operative.     

Influences of blood sampling procedures on basal hypothalamic-pituitary-adrenal hormone levels and leukocyte values in rhesus macaques (Macaca mulatta)

Abstract: The influences of housing location and temporal factors on the results of blood sampling were examined to determine their contributions to levels of hypothalamic-pituitary-adrenal hormones, as well as leukocyte subset counts from peripheral blood in rhesus monkeys. Differences in housing location and the amount of room disturbance associated with blood sampling have a significant impact on cell counts, but not on ACTH or Cortisol levels.     

Molecular Perspectives of SARS-CoV-2: Pathology,Immune Evasion,and Therapeutic Interventions

The outbreak of coronavirus disease 2019 (COVID-19) has not only affected human health but also diverted the focus of research and derailed the world economy over the past year. Recently, vaccination against COVID-19 has begun, but further studies on effective therapeutic agents are still needed. The severity of COVID-19 is attributable to several factors such as the dysfunctional host immune response manifested by uncontrolled viral replication, type I interferon suppression, and release of impaired cytokines by the infected resident and recruited cells. Due to the evolving pathophysiology and direct involvement of the host immune system in COVID-19, the use of immune-modulating drugs is still challenging. For the use of immune-modulating drugs in severe COVID-19, it is important to balance the fight between the aggravated immune system and suppression of immune defense against the virus that causes secondary infection. In addition, the interplaying events that occur during virus–host interactions, such as activation of the host immune system, immune evasion mechanism of the virus, and manifestation of different stages of COVID-19, are disjunctive and require thorough streamlining. This review provides an update on the immunotherapeutic interventions implemented to combat COVID-19 along with the understanding of molecular aspects of the immune evasion of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which may provide opportunities to develop more effective and promising therapeutics.     

Carotenoids in evolutionary ecology: re‐evaluating the antioxidant role

The antioxidant role of carotenoids in the living organism was proposed as a possible basis for the honesty of carotenoid‐based signals. However, recent studies have questioned the relevance of carotenoids as powerful antioxidants in vivo. Current evidence does not seem to support the “antioxidant role” hypothesis, but it does not allow us to reject it either. This paper proposes some steps to solve this controversy, such as taking a dynamic approach to antioxidant responses, designing protocols that expose individuals to oxidative challenges, analyzing tissues other than blood, and obtaining measures of antioxidant capacity and oxidative damage simultaneously. However, it should be considered that, irrespective of their antioxidant potential, carotenoids might still give information on oxidative stress levels if they are particularly sensitive to free radicals. Finally, lumping together the immunostimulatory and antioxidant roles of carotenoids should be avoided as these functions are not necessarily associated.     

右美托咪定联合舒芬太尼术后镇痛对卵巢癌根治术患者细胞免疫功能和炎症应激反应的影响

摘要 目的：探讨右美托咪定联合舒芬太尼术后镇痛对卵巢癌根治术患者细胞免疫功能和炎症应激反应的影响。方法：根据随机数字表法将2020年2月至2023年2月期间陕西省肿瘤医院120例择期行卵巢癌根治术的患者分为对照组（n=60，术后镇痛药物选用舒芬太尼）和研究组（n=60，术后镇痛药物选用右美托咪定联合舒芬太尼）。对比两组镇静（Ramsay镇静评分）、细胞免疫功能[CD3⁺、CD4⁺、CD8⁺、CD4⁺/CD8⁺]、镇痛情况[视觉模拟评分法（VAS）]、不良反应、炎症应激反应[白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）、皮质醇（Cor）和去甲肾上腺素（NE）]变化情况。结果：与对照组术后6 h、12 h、24 h、48 h 相比，研究组同时间点VAS评分更低，Ramsay镇静评分更高（P<0.05）。与对照组术后24 h相比，研究组同时间点CD3⁺、CD4⁺、CD4⁺/CD8⁺更高，CD8⁺更低（P<0.05）。两组不良反应发生率组间对比未见差异（P>0.05）。与对照组术后24 h相比，研究组同时间点IL-6、TNF-α、Cor、NE更低（P<0.05）。结论：右美托咪定联合舒芬太尼用于卵巢癌根治术患者术后镇痛，镇静、镇痛效果显著，同时还可减轻机体炎症应激反应，缓解免疫抑制。     

Early B-cell factors involve in the tumorigenesis and predict the overall survival of gastric cancer

Gastric cancer (GC) is a heavy health burden around the world, which is the fifth most frequent tumor and leads to the third most common cancer-related deaths. It is urgent to identify prognostic markers as the guideline for personalized treatment and follow-up. We accessed the prognostic value of Early B-cell factors (EBFs) in GC. A total of 415 GC tissues and 34 normal tissues from The Cancer Genome Atlas Stomach Adenocarcinoma (TCGA-STAD) cohort, 616 external patients from {"type":"entrez-geo","attrs":{"text":"GSE15459","term_id":"15459"}}GSE15459, {"type":"entrez-geo","attrs":{"text":"GSE22377","term_id":"22377"}}GSE22377, {"type":"entrez-geo","attrs":{"text":"GSE51105","term_id":"51105"}}GSE51105, {"type":"entrez-geo","attrs":{"text":"GSE62245","term_id":"62245"}}GSE62245 were enrolled for analysis. Univariate and multivariate Cox regression analyses were employed to evaluate the sole and integrative prognostic value of EBFs, respectively. Genetic alterations, DNA methylation of EBFs were also evaluated, as well as the involved signaling pathways. We revealed that increased EBFs associated with the poor prognosis of GC patients, the prognostic model was established in TCGA-STAD cohort, and validated in Gene Expression Omnibus (GEO) cohorts, with effectiveness in both HER2 positive and negative patients. DNA methylation was involved in the impact on prognosis. Cell cycle, immune-associated, and MAPK pathways were influenced by EBFs. Anti-CTLA4 immunotherapy is more suitable for EBFs determining high-risk groups, but not anti-PD-1/PD-L1 therapy. 5-Fluorouracil, methotrexate, vorinostat are suitable to inhibit the function of EBFs. Our new findings provide novel insight into the prediction of prognosis and clinical treatment of GC patients based on EBFs.