Apolipoprotein A-1 downregulation promotes basal-like breast cancer cell proliferation and migration associated with DNA methylation.

Apolipoprotein A-I (APOA1) performs different roles in different subtypes of breast cancer. It is hypothesized to function as a tumor suppressor in basal-like breast cancer (BLBC). However, the specific role of APOA1 in BLBC and its underlying mechanisms remain unknown. The findings of the present study demonstrated a positive correlation between the expression level of APOA1 and the overall survival of patients with BLBC. Ectopic expression of APOA1 effectively inhibits the proliferation and metastasis of BLBC cells in vitro, and these effects are closely related to DNA methylation. To the best of our knowledge, the present study is the first to report increased methylation of the promoter region and decreased methylation of the structural genes of APOA1 in BLBC cells. These alterations resulted in the downregulation of APOA1 expression and suppression of BLBC tumor growth. Collectively, the results of the present study suggested that APOA1 mRNA expression is negatively regulated by DNA methylation in BLBC. Therefore, low expression of APOA1 may be a potential risk biomarker to predict survival in patients with BLBC.

Relationship between TIM3 Expression on Peripheral T Lymphocytes and Post-Stroke Depression.

Background: T cell immunoglobulin and mucin domain-containing protein 3 (TIM3) is a regulatory molecule expressed on a variety of cell types, including CD3+ T cells. Few studies have been conducted to look into the correlation between TIM3 expression on peripheral T lymphocytes and post-stroke depression (PSD). Objective: To investigate the relationship between TIM3 expressions on peripheral T lymphocytes in PSD patients. Methods: Acute stroke patients without depression (NPSD) (n=65), PSD patients (n=23), and body mass index (BMI), age, and education-matched healthy controls (HC) (n=59) were enrolled. Using flow cytometry, TIM3 expression was examined in the peripheral CD3+ CD4+ and CD3+ CD8+ T lymphocytes. Evaluation of the depressive severity in PSD patients was assessed using a 17-item Hamilton Depression Rating Scale (HAM-D-17). We used enzyme-linked immunosorbent assay (ELISA) to determine the serum concentrations of IL-1ß, IL-6, IL-10, and IL-18. We further assessed the relationships between TIM3 expression, serum cytokine levels, and the HAM-D-17 scores. Results: CD3+ CD4+ T cells reduced significantly in PSD patients compared with the NPSD patients and HC. Both NPSD patients and PSD patients had a significant increase in TIM3 expression in their peripheral CD3+ CD4+ T lymphocytes, compared with HC. In PSD patients, a higher frequency of peripheral CD3+ CD8+ T lymphocytes showed significant expression of TIM3 compared to NPSD patients and HC. High TIM3 level on peripheral CD3+ CD8+ T lymphocytes was positively associated with the HAM-D score. Conclusion: Patients with PSD exhibit immune dysfunction. TIM3 might contribute to the development and severity of PSD, making it a potential therapeutic target.

Hydrazinocurcumin Induced Autophagy and Affected Cell Proliferation by Downregulating the JAK/STAT3 Signaling Pathway in Skin Squamous Cell Carcinoma.

This study aims to investigate the relevant mechanism by which hydrazinocurcumin (HC) interferes with A431 cell autophagy by inhibiting the STAT3 signaling pathway. Different concentrations of HC are used to treat A431 cells to study the effects of HC on A431 cell proliferation and apoptosis. Real-time fluorescent quantitative polymerase chain reaction (PCR) is used to further explore the relationship of HC with the JAK signaling pathway and autophagy. Double immunofluorescence staining is used to detect the fluorescence localization of LC3 and STAT3 after HC treatment. With increasing HC concentrations, A431 cell viability decreases in a dose-dependent manner, and the apoptosis rate increases significantly. Laser confocal colocalization reveals that the fluorescence of labeled LC3 protein is significantly increased, and the fluorescence of labeled STAT3 is significantly reduced in this study. HC may induce autophagy in A431 cells and affect cell proliferation by downregulating the JAK/STAT3 signaling pathway.

The Interaction Between Autophagy and JAK/STAT3 Signaling Pathway in Tumors.

Tumor is one of the important factors affecting human life and health in today's world, and scientists have studied it extensively and deeply, among which autophagy and JAK/STAT3 signaling pathway are two important research directions. The JAK/STAT3 axis is a classical intracellular signaling pathway that assumes a key role in the regulation of cell proliferation, apoptosis, and vascular neogenesis, and its abnormal cell signaling and regulation are closely related to the occurrence and development of tumors. Therefore, the JAK/STAT3 pathway in tumor cells and various stromal cells in their microenvironment is often considered as an effective target for tumor therapy. Autophagy is a process that degrades cytoplasmic proteins and organelles through the lysosomal pathway. It is a fundamental metabolic mechanism for intracellular degradation. The mechanism of action of autophagy is complex and may play different roles at various stages of tumor development. Altered STAT3 expression has been found to be accompanied by the abnormal autophagy activity in many oncological studies, and the two may play a synergistic or antagonistic role in promoting or inhibiting the occurrence and development of tumors. This article reviews the recent advances in autophagy and its interaction with JAK/STAT3 signaling pathway in the pathogenesis, prevention, diagnosis, and treatment of tumors.

Immunoregulatory role of IL-2/STAT5/CD4+CD25+Foxp3 Treg pathway in the pathogenesis of chronic osteomyelitis.

BACKGROUND: This study aimed to investigate immunoregulatory role of IL-2/STAT5/CD4+CD25+Foxp3 Treg pathway in pathogenesis of chronic osteomyelitis (COM). METHODS: Sprague-Dawley (SD) rats were injected with Staphylococcus aureus to establish COM model. 4 weeks later, the lesioned bones were collected and subjected to HE staining for examination of inflammatory infiltration. Enzyme-linked immunosorbent assay (ELISA) was employed to detect IL-2 expression in peripheral blood; flow cytometry was performed to detect CD25+CD4+Foxp3 Treg cells in peripheral blood. The mRNA expression of Foxp3 and CTLA-4 was detected by RT-PCR and the protein expression of STAT5 and p-STAT5 was detected by Western Blotting in CD25+CD4+Foxp3 Treg cells. RESULTS: In COM group, the periosteal thickening was observed in femur, and there were a large number of inflammatory cells in medullary cavity, accompanied by bone destruction. At 1, 2 and 4 weeks, IL-2 expression significantly increased, the proportion of CD4+CD25+FoxP3 Treg cells in peripheral monocytes markedly increased, the mRNA expression of Foxp3 and CTLA-4 and p-STAT5 protein expression increased dramatically in Treg cells as compared to control group (P<0.001). CONCLUSIONS: IL-2/STAT5/CD4+CD25+Foxp3 Treg pathway may be involved in the pathogenesis of COM, and excessive immunosuppression may lead to persistent infectious inflammation, which may become a key target for future treatment of COM.

Changes of circulating Th22 cells in children with hand, foot, and mouth disease caused by enterovirus 71 infection.

Interleukin (IL)-22+CD4+T (Th22) cells play crucial roles in the pathogenesis of autoimmune diseases and infectious diseases, although the role of Th22 cells remains largely unclear in children with hand, foot, and mouth disease (HFMD) caused by enterovirus 71 (EV71). This study aims to explore the role of circulating IL-22+IL-17A-CD4+T (cTh22) cells in children with EV71-associated HFMD. We found that during the acute stage of illness, the frequencies of cTh22 and circulating IL-22+IL-17A+CD4+T (IL-22+cTh17) cells in CD4+T cells infrom affected patients, and especially in severely affected patients, were significantly higher than in healthy controls (HC). The major source of IL-22 production was cTh22 cells, partially from cTh17 cells. Moreover, the protein and mRNA levels of IL-22, IL-17A, IL-23, IL-6, and TNF-α were significantly different among the mild patients, severe patients and HC, as well as AHR and RORγt mRNA levels. A positive correlation was found between plasma IL-22 levels and cTh22 cell frequencies, and cTh17 cell and IL-22+ cTh17 cell frequencies. Furthermore, the frequencies of cTh22 were significantly decreased in the convalescent patients. Our findings indicated that cTh22 cells could play critical roles in the pathogenesis of EV71 infection, and are potential therapeutic targets for patients with EV71-associated HFMD.