SARS-CoV-2 vaccines: A double-edged sword throughout rapid evolution of COVID-19.

After more than 2 years of the coronavirus disease 2019 pandemic caused by severe acute respiratory syndrome coronavirus 2, several questions have remained unanswered that affected our daily lives. Although substantial vaccine development could resist this challenge, emerging new variants in different countries could be considered as potent concerns regarding the adverse effects of reinfection or postvaccination. Precisely, these concerns address some significant and probable outcomes in vaccinated or reinfected models, followed by some virus challenges, such as antibody-dependent enhancement and cytokine storm. Therefore, the importance of evaluating the effectiveness of neutralizing antibodies (nAbs) elicited by vaccination and the rise of new variants must be addressed.

Methylation and Polymorphism in CDH1 Gene Promoter Among Patients with Diffuse Gastric Cancer.

Background: The promoter methylation and single nucleotide polymorphisms (SNPs) affect the transcription activity of cancer-related genes in several cancers including diffuse gastric cancer (DGC). Here we aimed to evaluate the promoter methylation status and the rs16260 at the promoter region of the CDH1 gene in DGC. Methods: This case-control study was performed of 48 formalin-fixed paraffin-embedded (FFPE) blocks of DGC patients and 41 fresh frozen tissue samples of healthy individuals. Methylation status was evaluated using methylation-specific polymerase chain reaction (PCR) and the rs16260 at the promoter region of the CDH1 gene was assessed using PCR and sequencing method. Results: The occurrence of methylation at the promoter region of the CDH1 gene in DGC patients was significantly higher than control samples (P < 0.0001). The methylated status was significantly associated with the poor differentiated histological type of DGC (P = 0.0428). The frequency of AC genotype and the A allele in DGC patients was significantly higher than the control subjects (P = 0.006 and 0.003, respectively). Conclusions: Here we showed that methylation at the CDH1 promoter may contribute to the DGC development, and also the AC genotype was associated with the risk of DGC.

T lymphocytes and preeclampsia: The potential role of T-cell subsets and related MicroRNAs in the pathogenesis of preeclampsia.

Innate and adaptive immune systems have a crucial role in initiating and progressing some pregnancy disorders such as preeclampsia (PE), which is one of the pregnancy-specific disorders that could result in neonatal and maternal morbidity and mortality. The dysregulation of the spiral artery and inadequate trophoblast invasion lead to PE symptoms through producing various inflammatory cytokines and anti-angiogenic factors from the placenta. T lymphocytes play a special role in the epithelium and stroma of the human endometrium. CD4+ T helper (Th) cells, Th1/Th2, and Th17/T regulatory (Treg) balance mainly contribute to the establishment of a pregnancy-favorable environment. This review examined the dysregulation of some cytokines produced from T cells, the dysregulation of the transcription factors of Th cells, the expression of chemokine receptors on T cells, as well as the effects of some factors including vitamin D on the activity of T cells, and finally, the dysregulation of various miRNAs related to T cells, which could cause PE.

A new approach to the preeclampsia puzzle; MicroRNA-326 in CD4+ lymphocytes might be as a potential suspect.

BACKGROUND: Alongside many complications in understanding the etiology of Preeclampsia (PE), several determinants, such as the imbalanced proportion of anti-angiogenic/proangiogenic T-cell subsets, especially CD4+ (Th17/Treg), as well as alterations in the expression profile of related cytokines, miRNAs, and transcription factors might have been implicated in PE pathogenesis. MATERIAL AND METHOD: After sample collection and preparation, CD4+ cells were isolated from PE and non-PE pregnant woman and were cultured. Furthermore, analysis such as flow cytometry, real-time PCR, western blotting, and ELISA were performed to assess determinants related to PE manifestation, including sFlt-1, sEng, STAT-3, RORγt, SMAD-7, Foxp3, IL-17, IL-22, Ets-1, and miRNA-326. RESULTS: Our results showed that the miRNA-326 expression level increased in CD4+ Cells and Th17 in PE patients which downregulated Ets-1 expression that acts as a negative control for Th17 development. Furthermore, we showed that the number and expression level of Th17 s and transcription factor RORγt escalated, respectively. While Treg and its related transcription factor (Foxp3) demonstrated a decrease. Flow cytometry analysis illustrated that the Th17/Treg ratio increased in PE. Additionally, we demonstrated that expression and concentration levels of cytokines (IL-17 and IL22) and anti-angiogenic molecules (sEng and sFlt-1) soared in isolated CD4+ cells from PE patients, which could be correlated with PE pathogenicity. CONCLUSION: In conclusion, we comprehensively evaluated immunological factors and molecules involved in PE manifestation. Interestingly, the CD4+ T-cell subset could be an extra source of antiangiogenic factors for the maintenance of this hypertension disorder.

A comparative study of long interspersed element-1 protein immunoreactivity in cutaneous malignancies.

BACKGROUND: Skin cancer is the most common cancer worldwide and commonly classified into malignant melanoma (MM) and Nonmelanoma skin cancers (NMSCs), which mainly include basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). The extent to which Long Interspersed Element-1 (LINE-1, L1) ORF1p is expressed in cutaneous malignancies remains to be evaluated. This study aimed to assess LINE-1 ORF1p immunoreactivity in various skin cancer subtypes. METHOD: The expression level of LINE-1 ORF1p was evaluated in 95 skin cancer specimens comprising 36 (37.9%) BCC, 28 (29.5%) SCC, and 31 (32.6%) melanoma using the tissue microarray (TMA) technique. Then the association between expression of LINE-1 encoded protein and clinicopathological parameters was analyzed. RESULTS: We showed that LINE-1 ORF1p expression level was substantially higher in BCC and SCC patients compared with melanoma samples (p < 0.001). BCC cases had a higher LINE-1 histochemical score (H-score) compared with SCC cases (p = 0.004). In SCC samples, a lower level of LINE-1 ORF1p expression was associated with age younger than the mean (p = 0.041). At the same time, no significant correlation was found between LINE-1 ORF1p expression and other clinicopathological parameters (all p > 0.05). CONCLUSIONS: According to our observation, LINE-1 ORF1p immunoreactivity in various skin tumor subtypes extends previous studies of LINE-1 expression in different cancers. LINE-1ORF1p overexpression in NMSCs compared with MM can be considered with caution as a tumor-specific antigen for NMSCs.

Expression of human endogenous retroviruses in pemphigus vulgaris patients.

Pemphigus is a severe, potentially life-threatening autoimmune blistering mucocutaneous disease which establishes with autoreactive IgG antibodies that target cellular adhesions, precisely extracellular domains of keratinocyte proteins. Several genetic and environmental elements are believed to contribute to the pathogenesis of the disease. The extent to which the initiation and progress of this autoimmune blistering disease may be influenced by the expression of human endogenous retroviruses (HERVs) remains to be elucidated. In this study, we evaluated the expression of HERV groups (K, W, and H) in pemphigus vulgaris (PV) patients in comparison to controls. Peripheral blood samples were collected from 24 PV patients and the corresponding age- and sex-matched healthy controls to extract total RNA for evaluation of HERV-K (HML-2), HERV-W, and HERV-H, env gene expression profile by qPCR. The mRNA expression level of HERV-K, HERV-W, and HERV-H were significantly upregulated in PV patients in comparison to healthy controls (P < 0.0001). The difference in expression of studied HERVs groups between men and women was no significant (P > 0.05). Although rituximab taking patients had a decreased expression level of studied HERVs, the results were not significant (P > 0.05). According to our obtained data, HERVs expression could be measured as a possible diagnostic tool for detection of PV and monitoring of the treatment.