Environmental pollutants and exosomes: A new paradigm in environmental health and disease.

This study investigates the intricate interplay between environmental pollutants and exosomes, shedding light on a novel paradigm in environmental health and disease. Cellular stress, induced by environmental toxicants or disease, significantly impacts the production and composition of exosomes, crucial mediators of intercellular communication. The heat shock response (HSR) and unfolded protein response (UPR) pathways, activated during cellular stress, profoundly influence exosome generation, cargo sorting, and function, shaping intercellular communication and stress responses. Environmental pollutants, particularly lipophilic ones, directly interact with exosome lipid bilayers, potentially affecting membrane stability, release, and cellular uptake. The study reveals that exposure to environmental contaminants induces significant changes in exosomal proteins, miRNAs, and lipids, impacting cellular function and health. Understanding the impact of environmental pollutants on exosomal cargo holds promise for biomarkers of exposure, enabling non-invasive sample collection and real-time insights into ongoing cellular responses. This research explores the potential of exosomal biomarkers for early detection of health effects, assessing treatment efficacy, and population-wide screening. Overcoming challenges requires advanced isolation techniques, standardized protocols, and machine learning for data analysis. Integration with omics technologies enhances comprehensive molecular analysis, offering a holistic understanding of the complex regulatory network influenced by environmental pollutants. The study underscores the capability of exosomes in circulation as promising biomarkers for assessing environmental exposure and systemic health effects, contributing to advancements in environmental health research and disease prevention.

Role of DIDO1 in Progression of Esophageal Squamous Cell Carcinoma.

PURPOSE: Apoptosis is one of the main involved processes during development and organogenesis and its aberration may result in tumorigenesis. In the present study, due to the role of death inducer-obliterator 1 (DIDO1) in activation of caspases 9 and 3 during the apoptosis process, the role of DIDO1 as the shortest splicing variant of the DIDO gene was assessed for the first time in esophageal squamous cell carcinoma (ESCC) patients. METHODS: DIDO1 mRNA expression in tumor tissues from 50 ESCC patients was compared to their corresponding margin normal tissues using the real-time polymerase chain reaction (RT-PCR). RESULTS: Nine out of 50 (18%) and 13 out of 50 (26%) cases had DIDO1 under- and overexpression, respectively. There was a significant correlation between DIDO1 mRNA expression and tumor depth of invasion (p = 0.050). Also, there was a significant correlation between age of patients and levels of DIDO1 mRNA expression (p = 0.039). CONCLUSIONS: This study is the first report that assessed the DIDO1 expression in ESCC patients and revealed its probable role in the early steps of tumor progression and metastasis. Therefore, DIDO1 can be suggested as a marker for the primary ESCCs.

Anticancer Activities of Cu(II) Complex-Schiff Base and Low-Frequency Electromagnetic Fields and the Interaction Between Cu(II) Complex-Schiff Base with Bovine Serum Albumin by Spectroscopy.

Cancer is the consequence of abnormal cell proliferation, which leads to the formation of abnormal mass. In this study, we aimed to determine the anticancer properties of Cu(II)-Schiff base complex and low-frequency electromagnetic field, and the interaction between BSA and Cu(II) complex. Firstly, Schiff base of the Cu(II) complex in the N,N'-dipyridoxyl(1,2 diaminobenzene) was originally synthesized. Following, the breast cancer was transplanted with the TUBO cells in vivo. Then, treatment of the cancerous mice was done by low-frequency electromagnetic field and the Cu(II)-Schiff base complex. In this project, antiproliferative activity on breast cancer cells was tested by TUBO cells using MTT assay and apoptosis properties were studied by flow cytometry. The interaction between the Cu(II)-Schiff base complex and bovine serum albumin (BSA) was checked by fluorescence and UV-vis absorbance spectroscopy. Tumor tissue investigation demonstrated that the low-frequency electromagnetic field and Cu(II)-Schiff base complex induce apoptosis and inhibit tumor growth. MTT results unveiled a cytotoxic impact on breast cancer cells. Flow cytometry analysis demonstrates that the anticancer effect of Cu(II)-Schiff base complex on breast cancer cells (MCF7) was associated with the cell cycle arrest. The results of fluorescence spectra and UV-vis absorption spectra showed that the conformation of bovine serum albumin has been changed in the presence of Cu(II)-Schiff base complex. Cu(II)-Schiff base complex and low-frequency electromagnetic field have anticancer properties. The spectroscopy method indicates the binding between Cu(II)-Schiff base complex and BSA.

Stemness state regulators SALL4 and SOX2 are involved in progression and invasiveness of esophageal squamous cell carcinoma.

Cancer stem cells, as a subgroup of tumor cells, resemble critical properties of embryonic stem cells (ESCs) such as self-renewal and maintenance of stemness state. SALL4 and SOX2 are two main transcription factors involving in maintenance of pluripotency, self-renewal and cell fate decision in ESCs. In this study, we aimed to elucidate the expression levels of these important transcription factors in esophageal squamous cell carcinoma (ESCC) and to reveal their probable roles in maintenance and progression of the disease. The expression level of SALL4 and SOX2 was analyzed in fresh tumoral tissues in comparison with distant tumor-free tissues of 50 ESCC patients by relative comparative real-time PCR. SALL4 and SOX2 were overexpressed in 64 and 32% of tumor samples, respectively, in significant correlation with each other (p = 0.028). There was a significantly inverse correlation between low level of SALL4 expression and metastasis of tumor cells into the lymph nodes (p = 0.035). Furthermore, co-overexpression of the genes was significantly correlated with the depth of tumor invasion (p = 0.045) and metastasis to the lymph nodes (p = 0.049). SALL4 and SOX2 are co-overexpressed in ESCC and have a significant correlation with invasion and metastasis of the disease. To the best of our knowledge, this is the first report of SALL4 clinical relevance in ESCC to date. The clinical consequences of SALL4-SOX2 association suggest a possible functional interaction between these factors in regulation of ESCC maintenance and aggressiveness and introduce these regulators of stemness state as potentially interesting therapeutic targets to bring new opportunities for onco-therapeutic modalities.