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Hashimoto's thyroiditis (HT) is an autoimmune disorder characterized by the destruction of thyroid follicular cells by thyroid peroxidase antibodies (TPOAb) and thyroglobulin antibodies (TgAb), leading to hypothyroidism. Hashimoto's encephalopathy (HE) is associated with elevated levels of antithyroid antibodies. An important question is whether brain alterations precede the development of HE and are present in euthyroid patients with HT, and what pathomechanisms could be responsible for these changes. A PubMed search was conducted to identify studies addressing this issue. Numerous questionnaire studies confirmed impairments in cognitive functioning, mental and physical health, and overall well-being in euthyroid HT patients. Additionally, some imaging and mouse model studies indicate that euthyroid patients with HT likely have central nervous system alterations. Antibodies may be involved in the development of these changes. Some research suggests the role of TPOAb and TgAb, while other studies highlight the involvement of coexisting antibodies. Determining whether antibodies are assessed in serum or cerebrospinal fluid (CSF) is crucial. Antibody-specific indices (ASIs) can differentiate between antibodies passively diffusing from the serum and brain-derived antibodies, and could serve as biomarkers for brain alterations in HT patients. Much more research is needed to identify reliable biomarkers and treatments that could improve the quality of life for these patients., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The study aimed to assess the expression of B7H3 concerning clinicopathological and histological parameters, including MSI/MSS status, CD-8 cells, tumour-infiltrating lymphocytes (TILs), budding, TNM scale and grading. Moreover, we analyzed the B7H3-related pathways using available online datasets and the immunological context of B7H3 expression, through the 48-cytokine screening panel of cancer tissues homogenates, immunogenic features and immune composition. The study included 158 patients diagnosed with CRC. To assess B7H3 levels, we performed an immunohistochemistry method (IHC) and enzyme-linked immunosorbent assay (ELISA). To elucidate the immune composition of colorectal cancer, we performed the Bio-Plex Pro Human 48-cytokine panel. To study biological characteristics of B7H3, we used online databases. Expression of B7H3 was upregulated in CRC tumour tissues in comparison to adjacent noncancerous margin tissues. The concentrations of B7H3 in tumours were positively associated with T parameter of patients and negatively with tumour-infiltrating lymphocytes score. Additionally, Principal Component Analysis showed that B7H3 expression in tumours correlated positively with cytokines associated with M2-macrophages and protumour growth factors. The expression of B7H3 in tumours was independent of MSI/MSS status. These findings will improve our understanding of B7H3 role in colorectal cancer immunity. Our study suggests that B7-H3 is a promising potential target for cancer therapy. Further studies must clarify the mechanisms of B7H3 overexpression and its therapeutic importance in colorectal cancer.

The study aimed to investigate correlations between HHLA2 levels and parameters, including microsatellite instability (MSI) status, CD8+ cells, and histopathological features: budding, tumor-infiltrating lymphocytes (TILs), TNM scale, grading, cytokines, chemokines, and cell signaling moleculesin colorectal cancer (CRC). Furthermore, the immune infiltration landscape and HHLA2-related pathways in colorectal cancer using available online datasets were analyzed. The study included 167 patients diagnosed with CRC. Expression of HHLA2 was detected by immunohistochemistry method (IHC) and enzyme-linked immunosorbent assay (ELISA). The IHC was used to evaluate the MSI and CD8+ status. The budding and TILs were measured using a light microscope. The concentrations of cytokines, chemokines, and cell signaling molecules were measured to analyze the data by the Bio-Plex Pro Human cytokine screening panel, 48 cytokine assay, and principal component analysis (PCA). Geneset enrichment analysis (GSEA) was conducted to identify HHLA2-related pathways. The biological function of HHLA2 was predicted by Gene Ontology (GO). Analysis of the immune infiltration landscape of HHLA2 in colorectal cancer was made by the web-based tool Camoip. High HHLA2 expression was detected in CRC tumor tissues compared to the adjacent noncancerous tissues. The percentage of HHLA2-positive tumors was 97%. GSEA and GO showed that HHLA2 upregulation correlated with cancer-related pathways and several biological functions. Tumor-infiltrating lymphocytes score correlated positively with IHC HHLA2 expression level percentage. There was a negative correlation between HHLA2, anti-tumor cytokines and pro-tumor growth factors. This study provides a valuable insight into the role of HHLA2 in CRC. We reveal the role of HHLA2 expression as well as a stimulatory and inhibitory immune checkpoint in colorectal cancer. Further research may verify the therapeutic values of the HHLA2-KIR3DL3/TMIGD2 pathway in colorectal cancer.

The immunotherapies based on ICIs in CRC are nowadays limited to microsatellite unstable tumours which are approximately 15% of all CRC cases. There are a few new immune checkpoints belonging to the B7 family, including B7H4. B7H4 expression is associated with so-called "cold tumours", and its function is linked to the downregulation of various immune cell populations. Our study aimed to investigate whether B7H4 expression is dependent on microsatellite status in CRC and on elucidating the immunological context in which the expression of B7H4 occurs. We enrolled 167 patients in the study. We prepared the homogenates from tumour tissues and healthy adjacent tissue to assess the B7H4 levels and the Bio-Plex Pro Human 48-cytokine panel. We assessed the microsatellite status of the tumour, B7H4 expression, CD8+ T cell population, and the TILs and budding in H + E stained slides by the IHC method. We used an online available database for further exploring the biological characteristics of B7H4. The expression of B7H4 was more frequent in microsatellite stable tumours, and was negatively associated with TILs. B7H4 is positively correlated with antitumour immunosuppressive iTME, thus contributing to the immunosuppressive environment in CRC.

Introduction: Many women of premenopausal age suffer from uterine leiomyomas, which are benign tumors of the uterus. Despite the high prevalence of uterine leiomyomas underlying pathogenesis mechanisms are not fully elucidated. Early data showed a positive correlation between increased levels of adipose tissue and leiomyomas prevalence. Adipose tissue cells-adipocytes can play a potential role in leiomyomas formation by producing and secreting adipokines., Aim: The aim of this study is to summarize the current knowledge on the potential relation between adipokines and leiomyomas basing on current data analyze, and justify future research directions., Methodology: This review is based on pertinent articles searched using PubMed, encompassing all available literature. The key search words were as follows: adipokines, leiomyoma, TNFα, leptin, adiponectin, visfatin, resistin, omentin, lipocalin, apelin, adipsin, chemerin. Time was not an exclusion criterium due to few available studies on this subject., Summary: The results of the studies are inconclusive, but the vast majority indicates a significant connection between the adipokines and the leiomyomas. According to the majority of studies, TNFα contributes to the development of leiomyomas by inhibiting apoptosis, increasing migration of leiomyomas, and increasing fibrosis of leiomyomas. Most of the studies on the effects of leptin also indicate the relation between leptin and leiomyomas development. In the case of adiponectin released from mast cells' granularity, it is possible that adiponectin increases angiogenesis in leiomyomas. Under physiological conditions, adiponectin has the potential to inhibit the development of leiomyomas. The authors suggested that adiponectin affects leiomyomas via an insulin-dependent pathway or via an estrogen-dependent pathway. Most probably leptin contributes to the formation of myomas and adiponectin prevents this. More research is needed to understand better the influence of these molecules on the pathogenesis of leiomyomas., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)