A novel approach to type 3 diabetes mechanism: The interplay between noncoding RNAs and insulin signaling pathway in Alzheimer's disease.

Today, growing evidence indicates that patients with type 2 diabetes (T2D) are at a higher risk of developing Alzheimer's disease (AD). Indeed, AD as one of the main causes of dementia in people aged more than 65 years can be aggravated by insulin resistance (IR) and other metabolic risk factors related to T2D which are also linked to the function of the brain. Remarkably, a new term called "type 3 diabetes" has been suggested for those people who are diagnosed with AD while also showing the symptoms of IR and T2D. In this regard, the role of genetic and epigenetic changes associated with AD has been confirmed by many studies. On the other hand, it should be noted that the insulin signaling pathway is highly regulated by various mechanisms, including epigenetic factors. Among these, the role of noncoding RNAs (ncRNAs), including microRNAs and long noncoding RNAs has been comprehensively studied with respect to the pathology of AD and the most well-known underlying mechanisms. Nevertheless, the number of studies exploring the association between ncRNAs and the downstream targets of the insulin signaling pathway in the development of AD has notably increased in recent years. With this in view, the present study aimed to review the interplay between different ncRNAs and the insulin signaling pathway targets in the pathogenesis of AD to find a new approach in the field of combining biomarkers or therapeutic targets for this disease.

Long noncoding RNAs biomarker-based cancer assessment.

Cancer diagnosis have mainly relied on the incorporation of molecular biomarkers as part of routine diagnostic tool. The molecular alteration ranges from those involving DNA, RNA, noncoding RNAs (microRNAs and long noncoding RNAs [lncRNAs]) and proteins. lncRNAs are recently discovered noncoding endogenous RNAs that critically regulates the development, invasion, and metastasis of cancer cells. They are dysregulated in different types of malignancies and have the potential to serve as diagnostic markers for cancer. The expression of noncoding RNAs is altered following many diseases, and besides, some of them can be secreted from the cells into the circulation following the apoptotic and necrotic cell death. These secreted noncoding RNAs are known as cell free RNA. These RNAs can be secreted from the cell through the apoptotic body, extracellular vesicles including microvesicle and exosome, and bind to proteins. Since, lncRNAs display high organ and cell specificity, can be found in the blood, urine, tumor tissue, or other tissues or bodily fluids of some patients with cancer, this review summarizes the most significant and up-to-date findings of research on lncRNAs involvement in different cancers, focusing on the potential of cancer-related lncRNAs as biomarkers for diagnosis, prognosis, and therapy.

Ginseng supplementation and cardiovascular disease risk factors: a protocol for GRADE-assessed systematic review and dose-response meta-analysis.

INTRODUCTION: Heart diseases constitute a significant global public health concern. Cardiovascular diseases (CVDs) are characterised by disruptions in blood circulation and are notably prevalent among adults exposed to Westernised diets. Ginseng, a medicinal plant, has been recognised for its healing properties and has a history of use spanning thousands of years. This systematic review aims to evaluate the efficacy of ginseng in modifying risk factors for CVD, including lipid profiles, glycaemic control, anthropometric indices, inflammation indicators, blood pressure, oxidative stress, liver function tests, adipokines and heart rate among individuals aged 18 and above, encompassing both genders. METHODS AND ANALYSIS: We will conduct an electronic search for articles published from inception to September 2023 using a predefined search strategy in PubMed, Scopus, Web of Science, CENTRAL and EMBASE. Our search will focus exclusively on randomised controlled clinical trials involving both healthy and unhealthy participants. The process of reviewing articles, extracting pertinent information and assessing the quality of studies using the Cochrane risk of bias tool will be carried out independently by two reviewers. Any discrepancies will be resolved through discussion with a third party. If a sufficient number of eligible studies are identified, a meta-analysis will be conducted using these outcomes. ETHICS AND DISSEMINATION: This study serves as the procedural framework for a comprehensive examination and does not require ethical approval. Additionally, the study adhered to the guidelines outlined in the Declaration of Helsinki. Ethical approval for the study was obtained from the Ethics Committee of Golestan University of Medical Sciences (IR.GOUMS.REC.1402.298). PROSPERO REGISTRATION NUMBER: CRD42023465688.

Expression Status of Rap1 Pathway-Related Genes in Liver Metastases Compared with Corresponding Primary Colorectal Cancer.

Understanding molecular networks of CRLM is an ongoing area of research. In this study, paired CRC tissue and adjacent noncancerous tissue from 15 non-metastatic CRC patients and paired CRC tissue and matched liver metastatic tissues from 15 CRLM patients along with their adjacent noncancerous tissues were evaluated. We assessed Rap1 pathway-related genes including NRAS, FGF-1, NGF, and KDR expression by qRT-PCR and their protein status by Western blot. In CRLM patients, NRAS, FGF1, and KDR mRNA and protein were expressed at higher levels in metastatic than in CRC primary tumor and adjacent noncancerous tissue (p < 0.05). In non-metastatic patients, NRAS, FGF1, KDR, and NGF gene expression did not differ between CRC primary tumor-and adjacent noncancerous tissue (p > 0.05). ROC curve analysis showed a reasonable diagnostic accuracy of NRAS, FGF1, KDR, and FGF for the discrimination of metastatic patients from non- metastatic ones on analysis of their primary tumors. The data suggest that further functional studies on Rap1-related genes' role in CRLM are needed. In conclusion, the present data broaden our knowledge about specific molecular characteristics of CRLM. An increased understanding of the molecular features of metastasis has the potential to create more successful treatment, or prevention, of metastasis, especially in multimodal primary tumor treatment.

Tumor-derived urinary exosomal long non-coding RNAs as diagnostic biomarkers for bladder cancer.

Bladder cancer (BC) is the sixth most common malignancy in men and 17th in women. Exosomal long non-coding RNAs (lncRNAs) have been defined as a novel biomarker for BC. The aim of this study is to evaluate the clinical significance of urine exosomal PVT-1, ANRIL and PCAT-1 as a biomarker in BC patients with tumors classified as T1 or T2. Exosomes were isolated from urine of BC patients and healthy donors, then characterized according to their shape, size, and exosome markers by Electron Microscopy, Dynamic light scattering, and Western blotting. Exosomal lncRNAs extraction was done to determine the expression levels of PVT-1, ANRIL and PCAT-1 by qRT-PCR. ANRIL and PCAT-1 expression was significantly higher in BC patients compared to normal subjects. To evaluate the performance of the identified lncRNAs for BC detection, we performed ROC curves analysis. The diagnostic accuracy of ANRIL and PCAT-1, measured by AUC, was 0.7229 (sensitivity = 46.67 % and specificity = 87.5 %) and 0.7292 (sensitivity = 43.33 % and specificity = 87.5 %). Transcript levels of lncRNAs in urinary exosomes are potential diagnostic biomarkers in bladder cancer.

lncRNA involvement in hepatocellular carcinoma metastasis and prognosis.

Eukaryotic lncRNAs are RNA molecules defined to be greater than 200 bp in length that are not translated to a protein and operate through several mechanisms, including participating in chromatin remodeling and methylation, influencing the integrity and stability of proteins and complexes, or acting as a sponge for miRNA inhibition. A number of recent studies have concentrated on the relationship between long non-coding RNAs (lncRNAs) and cancer. Hepatocellular carcinoma (HCC) is the most prevalent histological type of liver tumors, accounting for about 80 % of the cases worldwide. Lack of proper molecular markers for diagnosis of HCC and treatment evaluation is a significant problem. Dysregulated expression of HCC-related lncRNAs such as MEG-3, MALAT1, HULC, HOTAIR, and H19 have been identified and closely related with tumorigenesis, metastasis, prognosis and diagnosis. In this review, we summarized recent highlighted functions and molecular mechanisms of the most extensively studied lncRNAs in the pathophysiology of hepatocellular carcinoma and their potential for serving as probable therapeutic targets.

Multiple functions of p27 in cell cycle, apoptosis, epigenetic modification and transcriptional regulation for the control of cell growth: A double-edged sword protein.

The cell cycle is controlled by precise mechanisms to prevent malignancies such as cancer, and the cell needs these tight and advanced controls. Cyclin dependent kinase inhibitor p27 (also known as KIP1) is a factor that inhibits the progression of the cell cycle by using specific molecular mechanisms. The inhibitory effect of p27 on the cell cycle is mediated by CDKs inhibition. Other important functions of p27 include cell proliferation, cell differentiation and apoptosis. Post- translational modification of p27 by phosphorylation and ubiquitination respectively regulates interaction between p27 and cyclin/CDK complex and degradation of p27. In this review, we focus on the multiple function of p27 in cell cycle regulation, apoptosis, epigenetic modifications and post- translational modification, and briefly discuss the mechanisms and factors that have important roles in p27 functions.