Current Molecular Medicine
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Published By Bentham Science

1566-5240

2022 ◽  
Vol 22 ◽  
Author(s):  
Amira M. Gamal-Eldeen ◽  
Cinderella A. Fahmy ◽  
Bassem M. Raafat ◽  
Fayez Althobaiti ◽  
Iman H. Bassyouni ◽  
...  

Background: miR-210, a key HypoxamiR, regulates the hypoxia and inflammation-linked hypoxia. Systemic lupus erythematosus (SLE), a chronic autoimmune disease, responsible for many pathological disorders, including photosensitivity. Objective: Finding the correlation between the circulating miR-210/HIF-1α levels and photosensitivity in SLE patients and other SLE-associated pathological complications, in a single-center case control study. Methods: Study population of 104 SLE Egyptian patients with photosensitivity, 32 SLE patients without photosensitivity, and 32 healthy subjects. SLE activity was assessed for all patients by SLE Disease Activity Index (SLEDAI). The clinical complications/manifestations and the hematological/serological analyses were recorded. HIF-α concentration was investigated by ELISA and miR-210 expression was analyzed by qRT-PCR. Results: The results revealed that circulating miR-210 was significantly increased in SLE/photosensitivity than SLE and controls. The additional occurrence of malar rash, oral ulcers, renal disorders or hypertension resulted in a higher expression of miR-210. SLEDAI activity status showed no effect on miR-210. Erythrocyte sedimentation rate, white blood cells, hemoglobin, platelets, the patients age and the disease duration were positively correlated with circulatory miR-210. HIF-α concentration was significantly induced in SLE/photosensitivity than SLE and controls. In SLE/photosensitivity, presence of renal disorders and hypertension resulted in highest HIF-α concentrations. A strong positive correlation was recorded between HIF-α concentration and circulatory miR-210 in SLE/photosensitivity patients (r = 0.886). Conclusion:: The dysregulation of circulating miR-210/ HIF-1α levels in SLE/photosensitivity‎ patients is controlled by the presence of additional pathological complications and supposed that hypoxia pathway might interact positively with the pathogenesis and illness progress of SLE.


2022 ◽  
Vol 22 ◽  
Author(s):  
Anita A Pinar ◽  
Chrishan S S Samuel

Abstract: Inflammation and fibrosis are two inter‐related disease pathologies with several overlapping components. Three specific cell types, macrophages, T helper cells and myofibroblasts, each play important roles in regulating both processes. Following tissue injury, an inflammatory stimulus is often necessary to initiate tissue repair, where cytokines released from infiltrating and resident immune and inflammatory cells stimulate the proliferation and activation of extracellular matrix-producing myofibroblasts. However, persistent tissue injury drives an inappropriate pro‐fibrotic response. Additionally, activated myofibroblasts can take on the role of traditional antigen-presenting cells, secrete pro‐inflammatory cytokines, and recruit inflammatory cells to fibrotic foci, amplifying the fibrotic response in a vicious cycle. Moreover, inflammatory cells have been shown to play contradictory roles in the initiation, amplification and resolution of fibrotic disease processes. The central role of the inflammasome molecular platform in contributing to fibrosis is only beginning to be fully appreciated. In this review, we discuss the immune mechanisms that can lead to fibrosis, the inflammasomes that have been implicated in the fibrotic process in the context of the immune response to injury, and also discuss current and emerging therapies that target inflammasome-induced collagen deposition to treat organ fibrosis.


2022 ◽  
Vol 22 ◽  
Author(s):  
Muhammad Usman ◽  
Yasir Hameed ◽  
Mukhtiar Ahmad ◽  
Muhammad Junaid Iqbal ◽  
Aghna Maryam ◽  
...  

Aims: This study was launched to identify the SHMT2 associated Human Cancer subtypes. Background: Cancer is the 2nd leading cause of death worldwide. Previous reports revealed the limited involvement of SHMT2 in human cancer. In the current study, we comprehensively analyzed the role of SHMT2 in 24 major subtypes of human cancers using in silico approach and identified a few subtypes that are mainly associated with SHMT2. Objective:: We aim to comprehensively analyze the role of SHMT2 in 24 major subtypes of human cancers using in silico approach and identified a few subtypes that are mainly associated with SHMT2. Earlier, limited knowledge exists in the medical literature regarding the involvement of Serine Hydroxymethyltransferase 2 (SHMT2) in human cancer. Methods: In the current study, we comprehensively analyzed the role of SHMT2 in 24 major subtypes of human cancers using in silico approach and identified a few subtypes that are mainly associated with SHMT2. Pan-cancer transcriptional expression profiling of SHMT2 was done using UALCAN while further validation was performed using GENT2. For translational profiling of SHMT2, we utilized Human Protein Atlas (HPA) platform. Promoter methylation, genetic alteration, and copy number variations (CNVs) profiles were analyzed through MEXPRESS and cBioPortal. Survival analysis was carried out through Kaplan–Meier (KM) plotter platform. Pathway enrichment analysis of SHMT2 was performed using DAVID, while the gene-drug network was drawn through CTD and Cytoscape. Furthermore, in the tumor microenvironment, a correlation between tumor purity, CD8+ T immune cells infiltration, and SHMT2 expression was accessed using TIMER. Results: SHMT2 was found overexpressed in 24 different subtypes of human cancers and its overexpression was significantly associated with the reduced Overall survival (OS) and Relapse-free survival durations of Breast cancer (BRCA), Kidney renal papillary cell carcinoma (KIRP), Liver hepatocellular carcinoma (LIHC), and Lung adenocarcinoma (LUAD) patients. This implies that SHMT2 plays a significant role in the development and progression of these cancers. We further noticed that SHMT2 was also up-regulated in BRCA, KIRP, LIHC, and LUAD patients of different clinicopathological features. Pathways enrichment analysis revealed the involvement of SHMT2 enriched genes in five diverse pathways. Furthermore, we also explored some interesting correlations between SHMT2 expression and promoter methylation, genetic alterations, CNVs, tumor purity, and CD8+ T immune cell infiltrates. Conclusion: Our results suggested that overexpressed SHMT2 is correlated with the reduced OS and RFS of the BRCA, KIRP, LIHC, and LUAD patients and can be a potential diagnostic and prognostic biomarker for these cancers.


2022 ◽  
Vol 22 ◽  
Author(s):  
Suman Kumar Ray ◽  
Sukhes Mukherjee

Abstract: Deregulation of ubiquitin-mediated degradation of oncogene products or tumor suppressors appears to be implicated in the genesis of carcinomas, according to new clinical findings. Conferring to recent research, some members of the tripartite motif (TRIM) proteins (a subfamily of the RING type E3 ubiquitin ligases) act as significant carcinogenesis regulators. Intracellular signaling, development, apoptosis, protein quality control, innate immunity, autophagy, and carcinogenesis are all regulated by TRIM family proteins, the majority of which have E3 ubiquitin ligase activity. The expression of TRIMs in tumors is likely to be related to the formation and/or progression of the disease, and TRIM expression could be used to predict cancer prognosis. Breast cancer is the most common malignancy in women and also the leading cause of death. TRIM family proteins have unique, vital activities, and their dysregulation, such as TRIM 21, promotes breast cancer, according to growing evidence. Many TRIM proteins have been identified as important cancer biomarkers, with decreased or elevated levels of expression. TRIM29 functions as a hypoxia-induced tumor suppressor gene, revealing a new molecular mechanism for ATM-dependent breast cancer suppression. In breast cancer cells, the TRIM28-TWIST1-EMT axis exists, and TRIM28 enhances breast cancer metastasis by stabilizing TWIST1 and thereby increasing epithelial-to-mesenchymal transition. Interestingly, many TRIM proteins are involved in the control of p53, and many TRIM proteins are likewise regulated by p53, according to current research. Furthermore, TRIMs linked to specific tumors may aid in the creation of innovative TRIM-targeted cancer treatments. This review focuses on TRIM proteins that are involved in tumor development, progression, and clinical significance in breast cancer.


2022 ◽  
Vol 22 ◽  
Author(s):  
Moustafa M. Mohamed ◽  
Ahmed M. M. Okasha ◽  
Amany H. Abdel Naiem ◽  
Reham F. Mohamed ◽  
Sayed F. Abdelwahab ◽  
...  

Background: Autoimmune hepatitis (AIH) is an inflammatory liver disease which is characterized histologically by interface hepatitis, biochemically by elevated transaminase levels, and serologically by the presence of autoantibodies. Toll-like receptor (TLR)-4 is a TLR family member that, upon activation in hepatocytes, initiates a cascade of events. Interleukin-2 (IL-2) and tumour necrosis factor-α (TNF-α) are potent inflammatory cytokines secreted in AIH playing an important role in the early development of inflammation, and hepatocyte damage. Objective: This study examined cyclosporine role in AIH and tried to illustrate its actions on altered hepatic function in silica-induced AIH model. Methods: AIH was induced in Wester rats using Sodium Silicate. The rats were divided into four groups: control group, Silica-AIH group, cyclosporine-treated group, and prevention group. TLR-4, and IL-2 mRNA expression in liver tissues was tested by RT-PCR. Results: AIH was associated with up-regulation of liver enzymes, IL-2, and TLR-4 gene expression while cyclosporine significantly down-regulated the expression of both. The relative quantity of TLR-4 mRNA was 1±0, 13.57±1.91, 4±0.38, and 2±0 in the control, AIH, cyclosporine, and prevention groups, respectively (p<0.001). Also, the relative quantity of IL-2 mRNA was 1±0, 14.79±1.42, 7.07±0.96, and 3.4±0.55 in the same groups, respectively (p<0.001). Additionally, immuno-histochemical staining for TNF-α in liver sections was increased in the silica-AIH group but it was decreased in the cyclosporine-treated and prevention groups. Conclusion: This study advocates a therapeutic role of cyclosporine in treating immune-mediated hepatic diseases. Cyclosporine improves histological alterations in the liver and inhibits the production of proinflammatory cytokines.


2022 ◽  
Vol 22 ◽  
Author(s):  
Roghayyeh Baghban ◽  
Shirin Mahmoodi

Background: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has affected millions of people globally, in this regard, known as a pandemic by the World Health Organization (WHO). There is sufficient scientific evidence that a preventive COVID-19 vaccine is the most effective approach to combat with COVID-19 pandemic, therefore there is an essential need for safe and protective vaccines to fight it. Methods: Global efforts in developing a vaccine against COVID-19 have resulted in the development of different vaccine platforms with various safety and efficacy including live-attenuated vaccines, inactivated vaccines, subunit vaccines, and nucleic acid-based vaccines against coronavirus disease 2019 (COVID-19). Nucleic acid-based vaccines consist of mRNA and DNA vaccines have shown promising results in stimulating cellular and humoral immune responses properly against COVID-19, which their rapid and easy manufacturing process compared to others have made them considerable. mRNA-based vaccines platform by Pfizer/BioNtech and Moderna companies are the first approved vaccines for emergency use against COVID-19. Results: This narrative review highlights the recent advances in developing nucleic acid-based vaccines for COVID-19. Conclusion: The fast global dissemination of the coronavirus has highlighted the urgent necessity to build an efficient vaccine to inhibit disease. Cooperative attempts throughout the world have paid to the fast and unprecedented production of vaccines. Much needs to be learned regarding SARSCoV-2 and vaccine development against it.


2022 ◽  
Vol 22 (1) ◽  
pp. 1-1
Author(s):  
András Guttman


2021 ◽  
Vol 22 ◽  
Author(s):  
Azmi Yerlikaya ◽  
Sezgin Zeren

Abstract: According to the GLOBOCAN 2020 data, colorectal cancer is the third most commonly diagnosed cancer and the second leading cause of cancer-related death. The risk factors for colorectal cancer include a diet abundant with fat, refined carbohydrates, animal protein, low fiber content, alcoholism, obesity, long-term cigarette smoking, low physical inactivity, and aging. Colorectal carcinomas are classified as adenocarcinoma, neuroendocrine, squamous cell, adenosquamous, spindle cell, and undifferentiated carcinomas. In addition, many variants of colorectal carcinomas are recently distinguished based on histological, immunological, and molecular characteristics. Recently developed targeted molecules in conjunction with standard chemotherapeutics or immune checkpoint inhibitors provide promising treatment protocols for colorectal cancer. However, the benefit of targeted therapies is strictly dependent on the mutational status of signaling molecules (e.g., KRAS) or mismatch repair systems. Here it is aimed to provide a comprehensive view of colorectal cancer types, molecular pathways-associated, recently developed targeted therapies as well as proteomic investigations applied to colorectal cancer for the discovery of novel biomarkers as well as new targets for treatment protocols.


2021 ◽  
Vol 22 ◽  
Author(s):  
Idris Zubairu Sadiq

: Free radical contained one or more unpaired electrons in its valence shell, thus making it unstable, short-lived and highly reactive specie. Excessive generation of these free radicals ultimately leads to oxidative stress causing oxidation and damage to significant macromolecules in the living system and essentially disrupting signal transduction pathways and antioxidants equilibrium. At lower concentrations, ROS serves as “second messengers” influencing many physiological processes in the cell. However, at higher concentrations beyond cell capacity causes oxidative stress, which contributes to much human pathology such as diabetes, cancer, Parkinson’s disease, cardiovascular diseases, cataract, asthma, hypertension, atherosclerosis, arthritis and Alzheimer’s disease. Signaling pathways such as NF-κB, MAPKs, PI3K/Akt/ mTOR and Keap1-Nrf2-ARE modulates the detrimental effects of oxidative stress by increasing the expression of cellular antioxidant defenses, phase II detoxification enzymes and decreased production of ROS. Free radicals such as H2O2 are indeed needed for the advancement of cell cycle as these molecules influences DNA, proteins and enzymes in the cell cycle pathway. In the course of cell cycle progression, the cellular redox environment becomes more oxidized moving from G1 phase, becomes higher in G2/M and moderate in S phase. Signals in the form of an increase in cellular pro-oxidant levels are required and these signals are often terminated by a rise in the amount of antioxidants and MnSOD with a decrease in the level of cyclin D1 proteins. Therefore, understanding the mechanism of cell cycle redox regulation will help in therapy of many diseases.


2021 ◽  
Vol 22 ◽  
Author(s):  
Weiping Dong ◽  
Dong Zhang ◽  
Aiyun Zhu ◽  
Yanli Hu ◽  
Wei Li

Background: Dezocine is an opioid analgesic that can affect the immune system. Here, we explored the synergy of high concentration of Dezocine and Programmed death-ligand 1 (PD-L1) with regards to immune escape and glucose metabolism in lung cancer (LC). Methods: PD-L1 level in human LC cell lines was determined and the influence of Dezocine at different concentrations for the proliferation of LC cells was identified. Next, LC cells were transfected to alter PD-L1 level, and exposed to Dezocine at 8 μg/mL to explore their effects on cell proliferation, production of interferon-γ (IFN-γ), contents of glucose, lactate and NADPH/NADP+ and activation of the nuclear factor-κB (NF-κB) pathway. Results: PD-L1 level was increased in LC cells and Dezocine (8 μg/mL) impaired the proliferation of LC cells. Down-regulating PD-L1 inhibited cell proliferation, enhanced production of IFN-γ and reduced the contents of glucose, lactate and NADPH/NADP+ while up-regulating PD-L1 caused the opposite results. Dezocine (8 μg/mL) induced immune escape and glucose metabolism in LC, and Dezocine-induced effects were reversed by down-regulating PD-L1. Dezocine (8 μg/mL) up-regulated PD-L1 by activating the NF-κB pathway. Conclusion: Dezocine at 8 μg/mL promotes immune escape and glucose metabolism in LC through up-regulating PD-L1 and activating the NF-κB pathway.


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