Single-cell Technology in Stem Cell Research.

Single-cell technology (SCT), which enables the examination of the fundamental units comprising biological organs, tissues, and cells, has emerged as a powerful tool, particularly in the field of biology, with a profound impact on stem cell research. This innovative technology opens new pathways for acquiring cell-specific data and gaining insights into the molecular pathways governing organ function and biology. SCT is not only frequently used to explore rare and diverse cell types, including stem cells, but it also unveils the intricacies of cellular diversity and dynamics. This perspective, crucial for advancing stem cell research, facilitates non-invasive analyses of molecular dynamics and cellular functions over time. Despite numerous investigations into potential stem cell therapies for genetic disorders, degenerative conditions, and severe injuries, the number of approved stem cell-based treatments remains limited. This limitation is attributed to the various heterogeneities present among stem cell sources, hindering their widespread clinical utilization. Furthermore, stem cell research is intimately connected with cutting-edge technologies, such as microfluidic organoids, CRISPR technology, and cell/tissue engineering. Each strategy developed to overcome the constraints of stem cell research has the potential to significantly impact advanced stem cell therapies. Drawing from the advantages and progress achieved through SCT-based approaches, this study aims to provide an overview of the advancements and concepts associated with the utilization of SCT in stem cell research and its related fields.

The role of DNA methylation in progression of neurological disorders and neurodegenerative diseases as well as the prospect of using DNA methylation inhibitors as therapeutic agents for such disorders.

Genome-wide studies related to neurological disorders and neurodegenerative diseases have pointed to the role of epigenetic changes such as DNA methylation, histone modification, and noncoding RNAs. DNA methylation machinery controls the dynamic regulation of methylation patterns in discrete brain regions. Objective: This review aims to describe the role of DNA methylation in inhibiting and progressing neurological and neurodegenerative disorders and therapeutic approaches. Methods: A Systematic search of PubMed, Web of Science, and Cochrane Library was conducted for all qualified studies from 2000 to 2022. Results: For the current need of time, we have focused on the DNA methylation role in neurological and neurodegenerative diseases and the expression of genes involved in neurodegeneration such as Alzheimer's, Depression, and Rett Syndrome. Finally, it appears that the various epigenetic changes do not occur separately and that DNA methylation and histone modification changes occur side by side and affect each other. We focused on the role of modification of DNA methylation in several genes associated with depression (NR3C1, NR3C2, CRHR1, SLC6A4, BDNF, and FKBP5), Rett syndrome (MECP2), Alzheimer's, depression (APP, BACE1, BIN1 or ANK1) and Parkinson's disease (SNCA), as well as the co-occurring modifications to histones and expression of non-coding RNAs. Understanding these epigenetic changes and their interactions will lead to better treatment strategies. Conclusion: This review captures the state of understanding of the epigenetics of neurological and neurodegenerative diseases. With new epigenetic mechanisms and targets undoubtedly on the horizon, pharmacological modulation and regulation of epigenetic processes in the brain holds great promise for therapy.

The effect of tropisetron on oxidative stress, SIRT1, FOXO3a, and claudin-1 in the renal tissue of STZ-induced diabetic rats.

Tropisetron is a 5-HT3 receptor antagonist that exerts protective effect against DN. The aim of this study was to investigate the possible molecular mechanisms associated with the renoprotective effects of tropisetron in STZ-induced diabetic rats. Animals were subdivided into 5 equal groups; control, tropisetron, diabetes, tropisetron + diabetes, and glibenclamide + diabetes (n = 7). For induction of type 1 diabetes, a single injection of STZ (55 mg/kg, i.p.) was administered to the animals. Diabetic rats were treated with tropisetron (3 mg/kg) and glibenclamide (1 mg/kg) for 2 weeks. According to the conducted analysis, diabetes led to renal dysfunction (reduction in glomerular filtration rate and urine urea and creatinine as well as elevation in plasma urea and creatinine) and abnormalities in antioxidant defense system (reduction in TAC and elevation in MDA), compared with the control group, which was prevented by tropisetron treatment. Reverse transcription-quantitative polymerase chain reaction and western blotting analysis demonstrated that SIRT1 gene expression decreased while FOXO3a and NF-κB gene expression as well as phosphorylated FOXO3a/total FOXO3a protein ratios and claudin-1 protein level increased in the kidney of diabetic rats compared with the control group. Herein, the results of this research showed that tropisetron treatment reversed these changes. Besides, all these changes were comparable with those produced by glibenclamide as a positive control. Hence, tropisetron ameliorated renal damage due to diabetic nephropathy possibly by suppressing oxidative stress and alteration of SIRT1, FOXO3a, and claudin-1 levels.

EMT, cancer stem cells and autophagy; The three main axes of metastasis.

Epithelial-mesenchymal transition (EMT) and Cancer stem-like cells (CSCs) are major factors contributing to the metastasis of cancer cells. Consequently, the signaling pathways involved in both processes are appropriate therapeutic targets in the treatment of metastasis. Autophagy is another process that has recently attracted the attention of many researchers; depending on the type of cancer and tissue and the stage of cancer, this process can play a dual role in the development of cancer cells. Studies on cancer cells have shown that different signaling pathways are involved in all three processes, namely, cancer stem cells, autophagy, and EMT. The purpose of this study was to investigate and elucidate the relationship between the effective signaling pathways in all three processes, which could play an effective role in determining appropriate therapeutic goals.

The methylation status of TNF-α and SOCS3 promoters and the regulation of these gene expressions in patients with Behçet's disease.

Introduction: The aim of this study was to evaluate the methylation status of TNF-α and SOCS3 promoters in patients with BD and compare them with a healthy group.Method: This was a case-control study, in which 47 subjects with BD and 61 individuals as the control participated. Blood samples were collected from all the participants. Then, PBMCs were isolated using the Ficoll method and methylation of considered sites was investigated using the qMS-PCR technique after DNA extraction by the rapid genomic DNA extraction method and its analysis with Nano-drop.Results: The methylation and expression of TNF-α showed that the methylation level significantly declined in the patient in comparison with the healthy (p < 0.05). Moreover, the results on the mean expression showed that it significantly increased in the patient group, as compared with the healthy group (p < 0.05). In addition, the expression of the SOCS3 gene was not significantly different between the patients and healthy subjects while the level of SOCS3 methylation was significantly higher in the patient group than that in the healthy group (p < 0.05).Discussion: The present study revealed that the gene expression of TNF-alpha increased in BD patients, suggesting that TNF-alpha likely has a role in the pathogenesis of BD.

Alantolactone inhibits stem-like cell phenotype, chemoresistance and metastasis in PC3 cells through STAT3 signaling pathway.

BACKGROUND AND PURPOSE: Cancer stem cells (CSCs), as the subpopulation of cancer cells, are associated with carcinogenesis, chemoresistance, and metastasis in malignancies. Also, CSCs are considered as the major reason for treatment failure in prostate cancer (PCa). Alantolactone (ALT), exerts anticancer activity in different types of cancers. In the present study, the relationship between ALT and CSCs in PCa metastasis and the molecular mechanisms involved in the progression of PCa were investigated. EXPERIMENTAL APPROACH: In this study, to evaluate cell viability, MTT assay was performed. Then, PC3 cells were treated with nontoxic concentrations of ALT and after this step wound-healing assay, colony-formation assay and chemosensitization assay were applied to determine cell migration, the ability of colony formation, and chemoresistance, respectively. Also, real-time polymerase chain reaction and western blotting were used for the determination of genes and protein expression, respectively. FINDINGS/RESULTS: Our finding showed that ALT at nontoxic concentrations (0.01 and 0.1 µM) for 72 h suppressed the STAT3 phosphorylation and signaling pathway. Also, ALT was able to modulate the stemness of PCa cells through downregulation of expression of SOX2, Oct-4, Nanog, CD133, CD44, and upregulation of p53 expression. On the other hand, we further found that ALT in nontoxic concentrations sensitized PCa cells to cisplatin. CONCLUSION AND IMPLICATIONS: ALT combated the stemness of cancer cells and metastasis by antagonizing of STAT3 signaling pathway. In addition, ALT exhibited anti-metastatic properties and may have potential as a new chemotherapy agent for the reduction of PCa metastasis.

Application of sesquiterpene lactone: A new promising way for cancer therapy based on anticancer activity.

Cancer is one of the most dangerous diseases that are rapidly increasing globally. After heart disease, it is the second leading cause of death, accounting for seven million deaths each year. Chemotherapy is the use of cytotoxic drugs on cancer cells. But the use of common chemotherapy drugs poses a problem due their high side effects and low efficacy. As a result, efforts are on to find new potent compounds with low side effects. The compounds extracted from plants have been studied in this regard due to their prevalence. Sesquiterpene lactones are a group of natural compounds that were first detected in Asteraceae dark plants. These compounds exercise their effects by reacting with functional groups available on proteins and enzymes, especially the thiol group. Owing to the high side effects as an antitumor synthetic drugs, efforts are being made to find drugs with high efficiency and low side effects. Their high structural ranges have attracted the attention of many researchers as a potential source of new anticancer drugs.

Advances in Silver Nanotechnology: An Update on Biomedical Applications and Future Perspectives.

Nanotechnology is one of the most promising fields for producing new applications in nanotechnology, biotechnology, and medicine. However, only a few products have been used for nanotechnology, biotechnology, and medical purposes. Nanoparticles have been among the most usually applied nanomaterial in our health care system for hundreds of years. The most prominent nano product is nano silver which generally present at 1-100 nm in size in at least one dimension. Silver nanoparticles reveal remarkably unusual chemical, physical and biological properties and have been used for many different applications which detailed in this review. This review is focusing on the different form of silver nanoparticles and its nanotechnological, biotechnological and medical applications.