The role of miR-143/miR-145 in the development, diagnosis, and treatment of diabetes.

Objectives: Diabetes mellitus [DM], is a multifaceted metabolic disease, which has become a worldwide threat to human wellness. Over the past decades, an enormous amount of attention has been devoted to understanding how microRNAs [miRNAs], a class of small non-coding RNA regulators of gene expression at the post-transcriptional level, are tied to DM pathology. It has been demonstrated that miRNAs control insulin synthesis, secretion, and activity. This review aims to provide an evaluation of the use of miR-143 and miR-145 as biomarkers for the diagnosis and prognosis of diabetes. Methods: The use of miR-143 and miR-145 as biomarkers for the diagnosis and prognosis of diabetes has been studied, and research that examined this link was sought after in the literature. In addition, we will discuss the cellular and molecular pathways of insulin secretion regulation by miR-143/145 expression and finally their role in diabetes. Results: In the current review, we emphasize recent findings on the miR-143/145 expression profiles as novel DM biomarkers in clinical studies and animal models and highlight recent discoveries on the complex regulatory effect and functional role of miR-143/145 expression in DM. Conclusion: A novel clinical treatment that alters the expression and activity of miR-143/miR-145 may be able to return cells to their natural state of glucose homeostasis, demonstrating the value of using comprehensive miRNA profiles to predict the beginning of diabetes. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-023-01317-y.

Effects of HIIT training and HIIT combined with circuit resistance training on measures of physical fitness, miRNA expression, and metabolic risk factors in overweight/obese middle-aged women.

OBJECTIVE: The purpose of this study was to examine the effects of 10 weeks of high-intensity interval training (HIIT) and HIIT combined with circuit resistance training (HCRT) on selected measures of physical fitness, the expression of miR-9, -15a, -34a, -145, and - 155 as well as metabolic risk factors including lipid profiles and insulin resistance in middle-aged overweight/obese women. METHODS: Twenty-seven overweight/obese women aged 35-50 yrs. were randomized to HIIT (n = 14) or HCRT (n = 13) groups. The HIIT group performed running exercises (5 reps x 4 min per session) with active recovery between repetitions for 10 weeks with 5 weekly sessions. The HCRT group performed 10 weeks of HIIT and resistance training with 3 weekly HIIT sessions and 2 weekly HCRT sessions. Anthropometric measures (e.g., body mass), selected components of physical fitness (cardiovascular fitness, muscle strength), levels of miRNAs (miR-9, -15a, -34a, -145, and - 155), lipid profiles (total cholesterol; TC, Triglycerides; TG, low-density lipoprotein cholesterol; LDL-C and high-density lipoprotein cholesterol; HDL-C), and insulin resistance; HOMA-IR index, were measured at baseline and week 10. RESULTS: An ANOVA analysis indicated no significant group by time interactions (p > 0.05) for all anthropometric measures, and maximum oxygen consumption (VO2max). A significant group by time interaction, however, was found for the one-repetition maximum (IRM; p < 0.001, ES= 0.751 , moderate). A post-hoc test indicated an increase in the pre-to-post mean 1RM for HCRT (p = 0.001, ES = 1.83, large). There was a significant group by time interaction for miR-155 (p = 0.05, ES = 0.014, trivial). Levels for miR-155 underwent pre-to-post HIIT increases (p = 0.045, ES = 1.232, large). Moreover, there were also significant group by time interactions for TC (p = 0.035, ES = 0.187, trivial), TG (p < 0.001, ES = 0.586, small), LDL-C (p = 0.029, ES = 0.200, small) and HDL-C (p = 0.009, ES = 0.273, small). Post-hoc tests indicated pre-post HCRT decreases for TC (p = 0.001, ES = 1.44, large) and HDL-C (p = 0.001, ES = 1.407, large). HIIT caused pre-to-post decreases in TG (p = 0.001, ES = 0.599, small), and LDL-C (p = 0.001, ES = 0.926, moderate). CONCLUSIONS: Both training regimes did not improve cardiovascular fitness. But, HCRT improved lower/upper limb muscle strength, and HIIT resulted in an increase in miR-155 expression in peripheral blood mononuclear cells. Furthermore, HIIT and HCRT each improved selected metabolic risk factors including lipid profiles and glucose and insulin metabolism in overweight/obese middle-aged women. TRIAL REGISTRATION: OSF, October, 4th 2023. Registration DOI: https://doi.org/10.17605/OSF.IO/UZ92E . osf.io/tc5ky . "Retrospectively registered".

Human umbilical cord mesenchymal stem cell-derived exosomes alleviate the severity of experimental autoimmune encephalomyelitis and enhance lag-3 expression on foxp3 + CD4 + T cells.

BACKGROUND: Multiple sclerosis (MS) is a complex autoimmune disease that affects the central nervous system, causing inflammation, demyelination, and neurodegeneration. Understanding the dysregulation of Tregs, dynamic cells involved in autoimmunity, is crucial in comprehending diseases like MS. However, the role of lymphocyte-activation gene 3 (Lag-3) in MS remains unclear. METHODS: In this study, we explore the potential of exosomes derived from human umbilical cord mesenchymal stem cells (hUMSCs-Exs) as an immune modulator in experimental autoimmune encephalomyelitis (EAE), a model for MS. RESULTS: Using flow cytometry, our research findings indicate that groups receiving treatment with hUMSC-Exs revealed a significant increase in Lag-3 expression on Foxp3 + CD4 + T cells. Furthermore, cell proliferation conducted on spleen tissue samples from EAE mice using the CFSE method exposed to hUMSC-Exs yielded relevant results. CONCLUSIONS: These results suggest that hUMSCs-Exs could be a promising anti-inflammatory agent to regulate T-cell responses in EAE and other autoimmune diseases. However, further research is necessary to fully understand the underlying mechanisms and Lag-3's precise role in these conditions.

Application of CRISPR/Cas9 System in the Treatment of Alzheimer's Disease and Neurodegenerative Diseases.

Alzheimer's, Parkinson's, and Huntington's are some of the most common neurological disorders, which affect millions of people worldwide. Although there have been many treatments for these diseases, there are still no effective treatments to treat or completely stop these disorders. Perhaps the lack of proper treatment for these diseases can be related to various reasons, but the poor results related to recent clinical research also prompted doctors to look for new treatment approaches. In this regard, various researchers from all over the world have provided many new treatments, one of which is CRISPR/Cas9. Today, the CRISPR/Cas9 system is mostly used for genetic modifications in various species. In addition, by using the abilities available in the CRISPR/Cas9 system, researchers can either remove or modify DNA sequences, which in this way can establish a suitable and useful treatment method for the treatment of genetic diseases that have undergone mutations. We conducted a non-systematic review of articles and study results from various databases, including PubMed, Medline, Web of Science, and Scopus, in recent years. and have investigated new treatment methods in neurodegenerative diseases with a focus on Alzheimer's disease. Then, in the following sections, the treatment methods were classified into three groups: anti-tau, anti-amyloid, and anti-APOE regimens. Finally, we discussed various applications of the CRISPR/Cas-9 system in Alzheimer's disease. Today, using CRISPR/Cas-9 technology, scientists create Alzheimer's disease models that have a more realistic phenotype and reveal the processes of pathogenesis; following the screening of defective genes, they establish treatments for this disease.

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.

Methylation status of interleukin-6 gene promoter in patients with Behçet's disease / Estatus de la metilación del promotor del gen interleucina-6 en pacientes con síndrome de Behçet

BACKGROUND: IL-6 mRNA expression is significantly high in many autoimmune diseases such as Behçet's disease; this is often related with more aggressive phenotypes. Nevertheless, the essential molecular process for its high expression has not been completely realized. The aim of this study was undertaken to estimate the gene copy number variation and promoter methylation to IL-6's high expression. METHODS: This study was performed on 51 patients and 61 healthy controls. Initially, DNA and RNA were extracted from all specimens. Promoter methylation levels of IL-6 were evaluated by MeDIP-qPCR technique. Also, IL-6 gene expression was measured by Real-time PCR. After that, we evaluated the relationship between gene expression and methylation, as well as their relationship with clinical specification. RESULTS: As we expected, the expression level of IL-6 gene increased significantly in the patient group compared to the healthy subjects. Also, the relative promoter methylation level of the IL-6 mRNA was significantly lower in patient group compared to healthy group (p < 0.001). DISCUSSION: We disclosed that the promoter hypomethylation may be considered as one of the main defects for IL-6 mRNA high expression in patients with Behçet's disease

ANTECEDENTES: La expresión de ARNm de IL-6 es significativamente elevada en muchas enfermedades autoinmunes, tales como el síndrome de Behçet, y ello se relaciona a menudo con fenotipos más agresivos. Sin embargo, no se ha comprendido plenamente el proceso molecular esencial para esta expresión elevada. El objetivo de este estudio fue la estimación de la variación del número de copias del gen, y la metilación del promotor de la expresión elevada de IL-6. MÉTODOS: Este estudio se realizó en 51 pacientes y 61 controles sanos. Al inicio, se extrajo ADN y ARN de todas las muestras. Se evaluaron los niveles de metilación del promotor de IL-6 mediante la técnica MeDIP-qPCR. También se midió la expresión del gen IL-6 mediante PCR a tiempo real. Tras ello, evaluamos la relación entre la expresión del gen y la metilación, así como su relación con la especificación clínica. RESULTADOS: Según lo previsto, el nivel de expresión del gen IL-6 se incrementó significativamente en el grupo de pacientes, con respecto a los sujetos sanos. También encontramos que el nivel relativo de metilación del promotor de ARNm de IL-6 fue considerablemente menor en el grupo de pacientes, con respecto al grupo sano (p < 0,001). DISCUSIÓN: Concluimos que la hipometilación del promotor puede considerarse uno de los defectos principales de la expresión elevada de ARNm de IL-6, en los pacientes con síndrome de Behçet