Expression and Clinical Significance of ki-67, CD10, BCL6, MUM1, c-MYC, and EBV in Diffuse Large B Cell Lymphoma Patients.

INTRODUCTION: Diffuse large B cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma (NHL) in adults. Although studies regarding the association between the expression of Ki-67, CD10, BCL6, and MUM1 proteins, as well as c-MYC amplification and EBV status with clinicopathologic characteristics have rapidly progressed, their co-expression and prognostic role remain unsatisfactory. Therefore, this study aimed to investigate the association between the expression of all markers and clinicopathologic features and their prognostic value in DLBCL. Also, the co-expression of markers was investigated. METHODS: The protein expression levels and prognostic significance of Ki-67, CD10, BCL6, and MUM1 were investigated with clinical follow-up in a total of 53 DLBCL specimens (including germinal center B [GCB] and activated B cell [ABC] subtypes) as well as adjacent normal samples using immunohistochemistry (IHC). Besides, the clinical significance and prognostic value of c-MYC and EBV status were also evaluated through chromogenic in situ hybridization (CISH), and their correlation with other markers was also assessed. RESULTS: The results demonstrated a positive correlation between CD10 and BCL6 expression, with both markers being associated with the GCB subtype (P<0.001 and P=0.001, respectively). Besides, we observe a statistically significant association between MUM1 protein expression and clinicopathologic type (P<0.005) as well as a positive association between c-MYC and recurrence (P=0.028). Our survival analysis showed that patients who had responded to R-CHOP treatment had better overall survival (OS) and progression-free survival (PFS) than those who did not. CONCLUSION: Collectively, this study's results add these markers' value to the existing clinical understanding of DLBCL. However, further investigations are needed to explore markers' prognostic and biological roles in DLBCL patients.

Inhibitory effect of microRNA-21 on pathways and mechanisms involved in cardiac fibrosis development.

Cardiac fibrosis is a pivotal cardiovascular disease (CVD) process and represents a notable health concern worldwide. While the complex mechanisms underlying CVD have been widely investigated, recent research has highlighted microRNA-21's (miR-21) role in cardiac fibrosis pathogenesis. In this narrative review, we explore the molecular interactions, focusing on the role of miR-21 in contributing to cardiac fibrosis. Various signaling pathways, such as the RAAS, TGF-ß, IL-6, IL-1, ERK, PI3K-Akt, and PTEN pathways, besides dysregulation in fibroblast activity, matrix metalloproteinases (MMPs), and tissue inhibitors of MMPs cause cardiac fibrosis. Besides, miR-21 in growth factor secretion, apoptosis, and endothelial-to-mesenchymal transition play crucial roles. miR-21 capacity regulatory function presents promising insights for cardiac fibrosis. Moreover, this review discusses numerous approaches to control miR-21 expression, including antisense oligonucleotides, anti-miR-21 compounds, and Notch signaling modulation, all novel methods of cardiac fibrosis inhibition. In summary, this narrative review aims to assess the molecular mechanisms of cardiac fibrosis and its essential miR-21 function.

Unraveling cardiac fibrosis: insights into microRNA-21's key role and promising approaches for controlCardiac fibrosis poses a significant global health threat and plays a central role in cardiovascular diseases. This examination delves into recent research revealing the participation of microRNA-21 (MiR-21) in the progression of cardiac fibrosis, providing insight into its critical function in this process. The investigation explores diverse molecular interactions, underscoring MiR-21's contribution to the development of cardiac fibrosis. Various signaling pathways, including the Renin-Angiotensin-Aldosterone System, TGF-ß, IL-6, IL-1, ERK, PI3K-Akt, and PTEN pathways, coupled with disturbances in fibroblast activity, matrix metalloproteinases (MMPs), and tissue inhibitors of MMPs (TIMPs), contribute to cardiac fibrosis. MiR-21's influence on growth factor secretion, apoptosis, and endothelial-to-mesenchymal transition further emphasizes its crucial role. What adds promise to MiR-21 is its capacity for regulation, providing potential insights into controlling cardiac fibrosis. The review also investigates various methods to modulate MiR-21 expression, such as antisense oligonucleotides, anti-miR-21 compounds, and Notch signaling modulation ­ innovative approaches showing potential in inhibiting cardiac fibrosis. In summary, this narrative review aims to dissect the complex molecular mechanisms behind cardiac fibrosis, explicitly emphasizing the indispensable role of MiR-21. By comprehending these mechanisms, researchers can lay the groundwork for inventive interventions and therapeutic strategies to hinder cardiac fibrosis, ultimately contributing to advancing cardiovascular health.

Unraveling the potential of CD8, CD68, and VISTA as diagnostic and prognostic markers in patients with pancreatic ductal adenocarcinoma.

Introduction: Pancreatic cancer is a truculent disease with limited treatment options and a grim prognosis. Immunotherapy has shown promise in treating various types of cancer, but its effectiveness in pancreatic cancer has been lacking. As a result, it is crucial to identify markers associated with immunological pathways in order to improve the treatment outcomes for this deadly cancer. The purpose of this study was to investigate the diagnostic and prognostic significance of three markers, CD8, CD68, and VISTA, in pancreatic ductal adenocarcinoma (PDAC), the most common subtype of pancreatic cancer. Methods: We analyzed gene expression data from Gene Expression Omnibus (GEO) database using bioinformatics tools. We also utilized the STRING online tool and Funrich software to study the protein-protein interactions and transcription factors associated with CD8, CD68, and VISTA. In addition, tissue microarray (TMA) and immunohistochemistry (IHC) staining were performed on 228 samples of PDAC tissue and 10 samples of normal pancreatic tissue to assess the expression levels of the markers. We then correlated these expression levels with the clinicopathological characteristics of the patients and evaluated their survival rates. Results: The analysis of the GEO data revealed slightly elevated levels of VISTA in PDAC samples compared to normal tissues. However, there was a significant increase in CD68 expression and a notable reduction in CD8A expression in pancreatic cancer. Further investigation identified potential protein-protein interactions and transcription factors associated with these markers. The IHC staining of PDAC tissue samples showed an increased expression of VISTA, CD68, and CD8A in pancreatic cancer tissues. Moreover, we found correlations between the expression levels of these markers and certain clinicopathological features of the patients. Additionally, the survival analysis revealed that high expression of CD8 was associated with better disease-specific survival and progression-free survival in PDAC patients. Conclusion: These findings highlight the potential of CD8, CD68, and VISTA as diagnostic and prognostic indicators in PDAC.

Natural products and the balancing act of autophagy-dependent/independent ferroptosis in cancer therapy.

The control of biological cell death is essential for the body's appropriate growth. The resistance of cells to the apoptotic process presents a new difficulty in the treatment of cancer. To combat cancer cells, researchers are working to find new apoptotic pathways and components to activate. One of the processes of regulated cell death (RCD) is referred to as ferroptosis marked by a decline in the activity of lipid glutathione peroxidase 4 (GPX4) after the buildup of reactive oxygen species (ROS). Since lipid peroxidation is a crucial component of ferroptosis and is required for its start, numerous medicines have been studied, particularly for the treatment of cancer. In this context, autophagy is an additional form of RCD that can govern ferroptosis through shared signaling pathways/factors involved in both mechanisms. In this review, we will explore the molecular mechanisms underlying ferroptosis and its association with autophagy, to gain fresh insights into their interplay in cancer advancement, and the potential of natural products for its treatment.

Macrophage-Based Therapeutic Strategies in Hematologic Malignancies.

Macrophages are types of immune cells, with ambivalent functions in tumor growth, which depend on the specific environment in which they reside. Tumor-associated macrophages (TAMs) are a diverse population of immunosuppressive myeloid cells that play significant roles in several malignancies. TAM infiltration in malignancies has been linked to a poor prognosis and limited response to treatments, including those using checkpoint inhibitors. Understanding the precise mechanisms through which macrophages contribute to tumor growth is an active area of research as targeting these cells may offer potential therapeutic approaches for cancer treatment. Numerous investigations have focused on anti-TAM-based methods that try to eliminate, rewire, or target the functional mediators released by these cells. Considering the importance of these strategies in the reversion of tumor resistance to conventional therapies and immune modulatory vaccination could be an appealing approach for the immunosuppressive targeting of myeloid cells in the tumor microenvironment (TME). The combination of reprogramming and TAM depletion is a special feature of this approach compared to other clinical strategies. Thus, the present review aims to comprehensively overview the pleiotropic activities of TAMs and their involvement in various stages of cancer development as a potent drug target, with a focus on hematologic tumors.

The therapeutic effect of exosomes from mesenchymal stem cells on colorectal cancer: Toward cell-free therapy.

Colorectal cancer (CRC) is known for its high mortality rate and affects more men than women. The treatment requires invasive surgical interventions, however, the progression of CRC metastasis is difficult to control in most cases. Mesenchymal stem cells (MSCs) with their outstanding characteristics have been widely used in the treatment of degenerative diseases as well as cancers. They affect the tumor microenvironment through either cell-cell interactions or communications with their secretome. While stem cells may represent a dual role in tumor proliferation and progression, exosomes have attracted much attention as a cell-free therapy in CRC treatment. Exosomes derived from native or genetically modified MSCs, as well as exosomal microRNAs (miRNAs), have been evaluated on CRC progression. Moreover, MSC-derived exosomes have been used as a carrier to deliver anticancer agents in colorectal cancer. In this review, we overview and discuss the current knowledge in both stem cell-based and cell-free exosome therapy of CRC.