Immunogenic SARS-CoV-2 S and N Protein Peptide and Cytokine Combinations as Biomarkers for Early Prediction of Fatal COVID-19

Early indications of the likelihood of severe coronavirus disease 2019 COVID-19 can influence treatments and could improve clinical outcomes. However, knowledge on the prediction markers of COVID-19 fatality risks remains limited. Here, we analyzed and quantified the reactivity of serum samples from acute (non-fatal and fatal) and convalescent COVID-19 patients with the spike surface glycoprotein (S protein) and nucleocapsid phosphoprotein (N protein) SARS-CoV-2 peptide libraries. Cytokine activation was also analyzed. We demonstrated that IgM from fatal COVID-19 serum reacted with several N protein peptides. In contrast, IgM from non-fatal serum reacted more with S protein peptides. Further, higher levels of pro-inflammatory cytokines were found in fatal COVID-19 serum compared to non-fatal. Many of these cytokines were pro-inflammatory and chemokines. Differences in IgG reactivity from fatal and non-fatal COVID-19 sera were also demonstrated. Additionally, the longitudinal analysis of IgG reactivity with SARS-CoV-2 S and N protein identified peptides with the highest longevity in humoral immune response. Finally, using IgM antibody reactivity with S and N SARS-CoV-2 peptides and selected cytokines, we have identified a panel of biomarkers specific to patients with a higher risk of fatal COVID-19 compared with that of patients who survive. This panel could be used for the early prediction of COVID-19 fatality risk

Metadherin: A Therapeutic Target in Multiple Cancers

Altered expression of many genes and proteins is essential for cancer development and progression. Recently, the affected expression of metadherin (MTDH), also known as AEG-1 (Astrocyte Elevated Gene 1) and Lyric, has been implicated in various aspects of cancer progression and metastasis. Elevated expression of MTDH/AEG-1 has been reported in many cancers including breast, prostate, liver, and esophageal cancers, whereas its expression is low or absent in non-malignant tissues. These expression studies suggest that MTDH may represent a potential tumor associated antigen. MTDH also regulates multiple signaling pathways including PI3K/Akt, NF-κB, Wnt/β-catenin, and MAPK which cooperate to promote the tumorigenic and metastatic potential of transformed cells. Several microRNA have also been found to be associated with the increased MTDH expression in different cancers. Increased MTDH levels were linked to the tumor chemoresistance making it an attractive novel therapeutic target. In this review, we summarize data on MTDH function in various cancers

Immunological Perspective for Ebola Virus Infection and Various Treatment Measures Taken to Fight the Disease

Ebolaviruses, discovered in 1976, belongs to the Filoviridae family, which also includes Marburg and Lloviu viruses. They are negative-stranded RNA viruses with six known species identified to date. Ebola virus (EBOV) is a member of Zaire ebolavirus species and can cause the Ebola virus disease (EVD), an emerging zoonotic disease that results in homeostatic imbalance and multi-organ failure. There are three EBOV outbreaks documented in the last six years resulting in significant morbidity (&gt;32,000 cases) and mortality (&gt;13,500 deaths). The potential factors contributing to the high infectivity of this virus include multiple entry mechanisms, susceptibility of the host cells, employment of multiple immune evasion mechanisms and rapid person-to-person transmission. EBOV infection leads to cytokine storm, disseminated intravascular coagulation, host T cell apoptosis as well as cell mediated and humoral immune response. In this review, a concise recap of cell types targeted by EBOV and EVD symptoms followed by detailed run-through of host innate and adaptive immune responses, virus-driven regulation and their combined effects contributing to the disease pathogenesis has been presented. At last, the vaccine and drug development initiatives as well as challenges related to the management of infection have been discussed.</jats:p

Polymorphisms in the <i>MSH2</i> gene predict poor survival of North Indian lung cancer patients undergoing chemotherapy

Aim: To estimate if MSH2 polymorphisms, viz. rs63749993, rs2303425, rs2303426, rs4987188, rs2303428 and rs17217772, have any association with clinical outcomes in North Indian lung cancer patients. Materials &amp; methods: PCR-RFLP was used for genotyping 500 cases. Logistic regression and survival analysis was performed by utilizing MedCalc software. Results &amp; conclusion: Our study concluded, adenocarcinoma subjects having heterozygous genotype for rs2303425 have increased survival time (MST = 12.43, p = 0.03). In lung cancer patients undergoing paclitaxel therapy, heterozygous carriers for the rs17217772 polymorphism have reduced survival time (MST = 7.96 vs 2.63 months; HR = 2.09; p = 0.02). For rs63749993 polymorphism undergoing irinotecan therapy, subjects having mutant genotype showed poor survival (13.26 vs 6.06 months; HR = 5.37; p = 0.0004). The results suggest that MSH2 polymorphisms are involved in decreasing overall survival for patients undergoing platinum-based chemotherapy. </jats:p