COVID-19 mRNA BNT162b2 vaccine immunogenicity among children with a history of paediatric multisystem inflammatory syndrome temporally associated with COVID-19 (PIMS-TS).

We conducted a prospective cohort study of 20 patients with a history of paediatric multisystem inflammatory syndrome temporally associated with COVID-19 (PIMS group, median age seven years, 70% male) and 34 healthy controls without such a history (CONTROL group, median age eight years, 38% male) aged 5-12 years, to assess the immunogenicity of Pfizer-BioNTech COVID-19 mRNA BNT162b2 vaccine (Comirnaty®). Patients received two doses of COVID-19 mRNA BNT162b2 vaccine (10 ug/dose) 21 days apart. Pre-vaccine anti-S SARS-CoV-2 IgG antibodies were measured on the day of the first dose and at the median of 23 days after the second dose. The study was conducted during the COVID-19 wave dominated by the Omicron variant of the virus. Anti-NCP SARS-CoV-2 IgG antibodies were measured twice to evaluate incidents of infection during the study period. Pre-vaccine quantification of both types of antibodies allowed us to differentiate patients into COVID-19 naive and previously infected in order to compare hybrid immunity with vaccine-induced immunity. Before vaccination, anti-S IgG serum geometric mean concentration (GMC) was 61.17 BAU/ml in the PIMS group and 24.97 in the CONTROL group, while post-vaccination GMC was 3879.14 BAU/ml and 3704.87 BAU/ml, respectively, and did not significantly differ between the groups. Hybrid immunity (regardless of PIMS history) resulted in a higher concentration of SARS-CoV-2 anti-S antibodies after vaccination. Four (20%) of the children in the PIMS group and 11 (32%) in the CONTROL group got infected with SARS-CoV-2 during the study period, yet all of them asymptomatically, and this event has not significantly altered post-vaccination anti-S titers. In conclusion, COVID-19 vaccination was highly immunogenic in children, including those with a history of PIMS-TS; hybrid immunity overperforms vaccine-induced immunity in terms of serological response in children. However, vaccination effectiveness in preventing SARS-CoV-2 infections in children should be further evaluated.

COVID-19 mRNA BNT162b2 vaccine safety and B-cell and T-cell reactogenicity among children with a history of paediatric multisystem inflammatory syndrome temporally associated with COVID-19 (PIMS-TS) - preliminary study.

To assess the safety of Pfizer-BioNTech COVID-19 mRNA BNT162b2 vaccine (Comirnaty®) among patients with the anamnesis of paediatric inflammatory syndrome temporally associated with COVID-19 (PIMS-TS), we conducted a prospective cohort study of 21 patients with history of PIMS (PIMS group, median age 7.4 years, 71% male) and 71 healthy controls without such an anamnesis (CONTROL group, median age 9.0 years, 39% male) aged 5-18 years. Among them, 85 patients (all PIMS patients and 64 CONTROL patients) completed the two dose schedule of vaccination administered 21 days apart and 7 children in the CONTROL group received a single, age appropriate dose of a COVID-19 mRNA BNT162b2 vaccine during the study period. The frequency and character of reported adverse events (AEs) after each dose and results of flow cytometry (FC) 3 weeks after a second dose were compared between those groups. COVID-19 mRNA BNT162b2 vaccine safety profile was very good and comparable in both groups. No severe AEs were observed. 30% of all patients reported some general AE after any vaccine dose and 46% - some local AE. Frequency of reported AEs did not differ between groups except for local hardening at injection site, more common in PIMS group (20% vs 4% after any vaccine dose, p = 0,02). All AEs were benign, general AEs lasted up to 5 days and localised - up to 6 days after a vaccine dose. COVID-19 mRNA BNT162b2 vaccine did not induce any PIMS-like symptoms in any patient. We did not observe any significant T cells or B cells subset abnormalities in the PIMS group compared to the CONTROL group three weeks after a second dose except for terminally differentiated effector memory T cells that were higher in PIMS group (p < 0.0041). To sum up COVID-19 mRNA BNT162b2 vaccine in children with PIMS-TS was safe. Further studies are required to support our findings.

Preliminary Study on the Expression of Testin, p16 and Ki-67 in the Cervical Intraepithelial Neoplasia.

Cervical cancer is one of the most common malignant cancers in women worldwide. The 5-year survival rate is 65%; nevertheless, it depends on race, age, and clinical stage. In the oncogenesis of cervical cancer, persistent HPV infection plays a pivotal role. It disrupts the expression of key proteins as Ki-67, p16, involved in regulating the cell cycle. This study aimed to identify the potential role of testin in the diagnosis of cervical precancerous lesions (CIN). The study was performed on selected archival paraffin-embedded specimens of CIN1 (31), CIN2 (75), and CIN3 (123). Moderate positive correlation was observed between testin and Ki-67 as well as testin and p16 expression in all dysplastic lesions (r = 0.4209, r = 0.5681; p < 0.0001 for both). Statistical analysis showed stronger expression of the testin in dysplastic lesions vs. control group (p < 0.0001); moreover, expression was significantly higher in HSIL than LSIL group (p < 0.0024). In addition, a significantly stronger expression of testin was observed in CIN3 vs. CIN1 and CIN3 vs. CIN2. In our study, expression of Ki-67, p16, and testin increased gradually as the lesion progressed from LSIL to HSIL. The three markers complemented each other effectively, which may improve test sensitivity and specificity when used jointly.

Naturally Formed Chitinous Skeleton Isolated from the Marine Demosponge Aplysina fistularis as a 3D Scaffold for Tissue Engineering.

Tissue engineering (TE) is a field of regenerative medicine that has been experiencing a special boom in recent years. Among various materials used as components of 3D scaffolds, naturally formed chitinous materials seem to be especially attractive because of their abundance, non-toxic and eco-friendly character. In this study, chitinous skeleton isolated from the marine sponge Aplysina fistularis (phylum: Porifera) was used for the first time as a support for the cultivation of murine fibroblasts (Balb/3T3), human dermal fibroblasts (NHDF), human keratinocyte (HaCaT), and human neuronal (SH-SY5Y) cells. Characterization techniques such as ATR FTIR, TGA, and µCT, clearly indicate that an interconnected macro-porous, thermostable, pure α-chitin scaffold was obtained after alkali-acid treatment of air-dried marine sponge. The biocompatibility of the naturally formed chitin scaffolds was confirmed by cell attachment and proliferation determined by various microscopic methods (e.g., SEM, TEM, digital microscopy) and specific staining. Our observations show that fibroblasts and keratinocytes form clusters on scaffolds that resemble a skin structure, including the occurrence of desmosomes in keratinocyte cells. The results obtained here suggest that the chitinous scaffold from the marine sponge A. fistularis is a promising biomaterial for future research about tissues regeneration.

The Role of Testin in Human Cancers.

Testin is a protein expressed in almost all normal human tissues. It locates in the cytoplasm along stress fibers being recruited to focal adhesions. Together with zyxin and vasodilator stimulated protein it forms complexes with various cytoskeleton proteins such as actin, talin and paxilin. They jointly play significant role in cell motility and adhesion. In addition, their involvement in the cell cycle has been demonstrated. Expression of testin protein level correlates positively with percentage of cells in G1 phase, while overexpression can induce apoptosis and decreased colony forming ability. Decreased testin expression associate with loss by cells epithelial morphology and gain migratory and invasive properties of mesenchymal cells. Latest reports indicate that TES is a tumor suppressor gene which can contribute to cancerogenesis but the mechanism of loss TES gene expression is still unknown. Some authors point out hypermethylation of the CpG island as a main factor, however loss of heterozygosity may also play an important role [4, 5]. The altered expression of testin was found in malignant neoplasm, i.a. ovarian, lung, head and neck squamous cell cancer, breast, endometrial, colorectal, prostate and gastric cancers [1-9]. Testin participate in the processes of tumor growth, angiogenesis, and metastasis [10]. Many researchers stated involvement of testin in tumor progression, what suggest its potential usage in immunotherapy [7, 11]. Understanding the molecular functions of testin may be crucial in development personalized treatment. In the present manuscript up-to-date review of literature can be found.

Expression of COX-2, IL-1ß, TNF-α and IL-4 in epithelium of serrated adenoma, adenoma and hyperplastic polyp.

INTRODUCTION: Colon polyps and inflammatory process play the key role in neoplasia of colorectal cancer. In recent years there have been many publications on the malignancy of hyperplastic polyp (HP) which according to the WHO classification is a non-neoplastic polyp. The aim of this study is to determine the expression of inflammatory proteins COX-2, IL-1ß, TNF-α and IL-4 in the epithelium of colorectal polyps. MATERIAL AND METHODS: In the study, 144 colorectal polyps were analyzed. The groups of HP, classical (A) and serrated adenomas (SA) and normal mucosa (control) according to histopathological studies were selected. Immunohistochemical examinations Rusing antibodies against COX-2, IL-1ß, TNF-α and IL-4 were performed. The expression of analyzed protein was evaluated using modified Remmele-Stegner scale (0-16). RESULTS: Statistical analysis revealed higher expression of TNF-α (16 ±3.87 vs. 1 ±5.06), IL-1ß (12 ±4 vs 8 ±2.72), COX-2 (9 ±2.54 vs. 8 ±3.14) and IL-4 (12 ±3.45 vs. 4 ±3.35) in SA polyps compared to the control (p < 0.001). The HP had an increased level of expression of TNF-α (12 ±3.72 vs. 1 ±5.06, p < 0.005), COX-2 (8.5 ±1.97 vs. 8 ±3.14, p < 0.012) and IL-4 (12 ±3.46 vs. 4 ±3.35, p < 0.001). Significantly higher expression of IL-4 (12 ±2.32 vs. 4 ±3.35, p < 0.001) and IL-1ß (16 ±4.32 vs. 8 ±2.72, p < 0.044) in A compared to the control were observed. CONCLUSIONS: Expression of inflammatory factors differed between polyps. Inflammation accompanied the serrated structures which occur in polyps. The inflammatory process affects the development of colorectal polyps. The HP may predispose to malignancy.

Large Bowel Genetic Background and Inflammatory Processes in Carcinogenesis--Systematic Review.

Colorectal cancer (CRC) has become the third most common cancer in developed countries. Each year more and more people die from CRC. CRC is also one of the most effectively studied topics in recent years. It has been found that the key phenomena in CRC development are genetic and inflammatory processes. Well-known genetic bases for the carcinogenesis of CRC include chromosomal changes characteristic of the chromosomal instability pathway which correlates with specific and well-defined genetic alterations (such as APC, K-RAS, DCC and p53) and genomic instability characteristics for the mutator pathway focused on KRAS and BRAF mutations. Recent studies have highlighted the impact of inflammation in CRC, especially elevated levels of pro-inflammatory cytokines. Among important risk factors of colon carcinogenesis are colorectal polyps, which are currently the subject of intense research. Recent studies have shown that different adenomas are characterized by different pathways of carcinogenesis as well as diverse COX-2 expression in various polyps. Understanding the mechanism of inflammatory processes in CRC parallel to basic genetic alterations might allow for effective and targeted treatment.

Serrated polyps and their alternative pathway to the colorectal cancer: a systematic review.

Colorectal cancer (CRC) is the third most frequently diagnosed cancer in the world. For a long time, only one pathway of colorectal carcinogenesis was known. In recent years, a new "alternative" pathway through serrated adenoma was described. Recent meta-analysis estimated these cancers as about 10% to 30% of all CRCs. Serrated polyps are the second most popular groups of polyps (after conventional adenomas) found during colonoscopy. Serrated polyps of the colon are clinically and molecularly diverse changes that have common feature as crypt luminal morphology characterized by glandular serration. Evidence suggests that subtypes of serrated polyps, particularly TSA and SSA/P, can lead to adenocarcinoma through the serrated pathway. Moreover, the data indicate that the SSA/P are the precursors of colorectal carcinoma by MSI and may be subject to rapid progression to malignancy. An important step to reduce the incidence of CRC initiated by the serrated pathway is to improve the detection of serrated polyps and to ensure their complete removal during endoscopy. Understanding of the so-called serrated carcinogenesis pathway is an important step forward in expanding possibilities in the prevention of CRC.