In its classical view, the renin angiotensin system (RAS) was defined as an endocrine system involved in blood pressure regulation and body electrolyte balance. However, the emerging concept of tissue RAS, along with the discovery of new RAS components, increased the physiological and clinical relevance of the system. Indeed, RAS has been shown to be expressed in various tissues where alterations in its expression were shown to be involved in multiple diseases including atherosclerosis, cardiac hypertrophy, type 2 diabetes (T2D) and renal fibrosis. In this chapter, we describe the new components of RAS, their tissue-specific expression, and their alterations under pathological conditions, which will help achieve more tissue- and condition-specific treatments.

Background and Aims: Several studies were performed to evaluate the relationship between CBC and patients with diabetes mellitus (DM). In this review, we discussed the prognostic value of CBC parameters in DM patients.Methods: English literature was searched and retrieved from the Google Scholar search engine and PubMed database (1980–2024). “Diabetes mellitus,” “Blood cell count,” “Mean platelet volume,” “Leukocytes,” and “Inflammation” were used as keywords.Results: DM increases vascular inflammation and oxidative stress, while vascular inflammation affects erythropoiesis and red blood cell deformation, thus increasing red cell distribution width (RDW). Mean platelet volume (MPV) is another useful prognostic biomarker for DM patients. Additionally, elevated neutrophil‐lymphocyte ratio (NLR) levels are associated with poor glycemic control in T2DM patients, so it can be used as a screening tool in diabetic follow‐up.Conclusion: RDW can be used as a valuable independent biomarker to assess the prognosis of patients with DM. MPV can also be used as a noninvasive, widely available, and low‐cost marker as a key factor as well as a Prognostic/diagnostic biomarker that could be used for DM patients. Total white blood cell count, NLR, Mean platelet volume lymphocyte ratio (MPVLR), and monocyte to high‐density lipoprotein ratio (MHR) are valuable biomarkers in predicting DM.

Cardiovascular disease (CVD) is one of the most common diseases worldwide. The underlying pathogenesis of the disease has not yet been determined, but many factors have been identified. Tet methylcytosine dioxygenase 2 (TET2) is one of the epigenetic factors involved in regulating many genes. Therefore, based on the studies shown, this factor plays an important role in preventing the occurrence of CVD. TET2 has been shown to increase angiogenesis by expressing Robo4. It also increases the activity of Matrix metalloproteinases (MMPs) and stimulates the secretion of Vascular endothelial growth factor angiogenesis. On the other hand, it has been shown that TET2 regulates the expression of several genes and the development of the heart during the embryonic period due to its oxygenating role. TET2 has been shown to regulates the expression of the genes such as Ying Yang1 (YY1), Sox9b, Inhbaa and many other genes that ultimately lead to the differentiation of cardiomyocytes. On the other hand, it has been shown that some Long non coding RNA and MicroRNAs reduce TET2 expression and CVD. Finally, it is concluded that inducing TET2 expression can be a good therapeutic strategy to prevent or improve CVD.

Glioblastoma is a brain tumor that develops due to both genetic and epigenetic risk factors. Crosstalk between the genetic and the epigenetic offers new possibilities for therapy. Abnormal methylation of methylguanine-DNA methyltransferase (MGMT) promoter region and isocitrate dehydrogenase 1 (IDH1) mutations are prognostic and therapeutic response markers in glioblastoma. Mutations in genes such as epidermal growth factor receptor, TP53, and P16 have been reported in glioblastoma; therefore, they might associate with survival and worth to be used in estimating survival risks. MKI67 expression associates with posttreatment such as adjuvant radiotherapy results evaluation. On the other hand, monosomies, such as deletions of chromosome 10, especially q23 and q25-26, are good markers for estimating the progression and aggressiveness of glioblastoma. The profile of MGMT methylation is modified in glioblastoma and hence can be a good target for epigenetic drugs. Other useful strategies in the treatment of gliomas include several micro-RNAs (MiRs) which are alerted in glioblastoma and which affect the regulation of mRNAs are associated with gene expression profiles of the disease. Epigenetic drugs, such as azacitidine and decitabine, which belong to the DNA methyltransferases (DNMT) inhibitor 5-aza-2' deoxycytidine (5-aza-dC), can suppress DNMT1 and stimulate tumor suppressor genes expression. MGMT methylation status and IDH mutational status are two valuable prognosis and therapeutic response markers in glioblastoma. Regulation of glioblastoma through epigenetic drugs, such as not only inhibitors of EZH2, histone deacetylase, and DNMT, but also MiRs, are promising approaches in glioblastoma treatment. Improves in understanding cancer genetic and epigenetic disruptions is the key point in solving the puzzle of glioblastoma treatment.