The emerging role of brain neuroinflammatory responses in Alzheimer's disease.

As the most common cause of dementia, Alzheimer's disease (AD) is characterized by neurodegeneration and synaptic loss with an increasing prevalence in the elderly. Increased inflammatory responses triggers brain cells to produce pro-inflammatory cytokines and accelerates the Aß accumulation, tau protein hyper-phosphorylation leading to neurodegeneration. Therefore, in this paper, we discuss the current understanding of how inflammation affects brain activity to induce AD pathology, the inflammatory biomarkers and possible therapies that combat inflammation for AD.

The neuroinflammatory role of microglia in Alzheimer's disease and their associated therapeutic targets.

INTRODUCTION: Alzheimer's disease (AD), the main cause of dementia, is characterized by synaptic loss and neurodegeneration. Amyloid-ß (Aß) accumulation, hyperphosphorylation of tau protein, and neurofibrillary tangles (NFTs) in the brain are considered to be the initiating factors of AD. However, this hypothesis falls short of explaining many aspects of AD pathogenesis. Recently, there has been mounting evidence that neuroinflammation plays a key role in the pathophysiology of AD and causes neurodegeneration by over-activating microglia and releasing inflammatory mediators. METHODS: PubMed, Web of Science, EMBASE, and MEDLINE were used for searching and summarizing all the recent publications related to inflammation and its association with Alzheimer's disease. RESULTS: Our review shows how inflammatory dysregulation influences AD pathology as well as the roles of microglia in neuroinflammation, the possible microglia-associated therapeutic targets, top neuroinflammatory biomarkers, and anti-inflammatory drugs that combat inflammation. CONCLUSION: In conclusion, microglial inflammatory reactions are important factors in AD pathogenesis and need to be discussed in more detail for promising therapeutic strategies.

Interleukin-6 inhibitory effect of natural product naringenin compared to a synthesised monoclonal antibody against life-threatening COVID-19.

Coronavirus Disease 2019 (COVID-19) has become a global pandemic in 2020 with high patient mortality due to acute respiratory distress syndrome which is possibly induced by a Cytokine release syndrome and more specifically through an interleukin-6 (IL-6) booster. Currently, IL-6/IL-6R inhibitors indicated an effective function in reducing the inflammatory markers in severe COVID-19 patients. In this comprehensively narrative review, we searched online academic databases including (Google Scholar, Web of Science, and Pub Med), the relevant literature was extracted from the databases by using search terms of COVID-19, IL-6, and IL6 inhibitor as free-text words and also with the combination with OR/AND to summarise the latest discoveries on the inhibitors of IL-6 and its receptor's especially focussing on the role of natural product, Naringin (NAR) as a flavonoid found in citrus fruits, with considerable anti-inflammatory and antiviral properties in COVID-19 treatments. Our data Therefore in comparison with other synthetic monoclonal antibodies NAR may provide a good qualification for the development of novel anti-inflammatory agents, especially against Covid 19 based on recent studies.

Prospective role of PD-1/PD-L1 immune checkpoint inhibitors in GI cancer.

One of the mechanisms by which tumor cells can evade the immune system is over activation of the programmed cell death protein-1 (PD-1) / programmed death-ligand 1 (PD-L1) pathway. The binding of PD-1 to its ligand PD-L1 can trigger an inhibitory signal for reducing T-cell proliferation, inhibiting the anticancer effect of T cells, and limiting the anti-tumor immunity of effectors T cell responses to protect tissues from immune-mediated tissue damage in the tumor microenvironment (TME). PD-1/PD-L1 immune checkpoint inhibitors have created a new pattern in cancer immunotherapy and can increase T cell- surveillance; therefore, the development of better clinical application of PD-1/PD-L1 inhibitors can significantly enhance antitumor immunity and prolong survival in GI cancer patients.

A comprehensive review of the role of LINC00462 in human disorders.

LINC00462; a long intergenic non-coding RNA located on chromosome chr13:48,576,973-48,590,587 is a member of long non-coding RNA (lncRNA) that is participated in different human disorders such as pancreatic cancer and hepatocellular carcinoma. LINC00462 can act as competing endogenous RNAs (ceRNAs), to sponge different MicroRNAs (miRNAs) such as miR-665. Dysregulation of LINC00462 can promote cancer development, progression, and metastasis. LINC00462 can also bind directly with genes and proteins to regulate different pathways, including STAT2/3 and PI3K/AKT pathways to affected tumor progression. In addition, aberrant LINC00462 levels can be important cancer-specific prognostic and diagnostic markers. In this review, we summarize the most recent studies on the role of LINC00462 in different disorders and demonstrated the role of LINC00462 in tumorigenesis.

Simvastatin Therapy Increased miR-150-5pExpression in the Patients with Type 2 Diabetes and COVID-19.

BACKGROUND/AIMS: Corona virus disease 2019 (COVID-19) has become a deadly infectious disease, especially for those with co-morbidities such as diabetes. People with diabetes developing a viral infection, seem to have harder treatments due to fluctuations in blood glucose levels therefore, effective therapeutic approaches need to be considered for them. Statins are well-known lipid-lowering drugs; they also have anti-inflammatory and immunomodulatory effects and can impact on expression of microRNAs (miRNAs). METHODS: In this study we investigate the effects of simvastatin on the expression of miR-150-5p as a famous regulator of inflammation and its association with multiple cancers in 30 patients with Type 2 diabetes mellitus (T2DM) and COVID-19 compared to the COVID-19 hospitalized patients before and after treatment with simvastatin with real-time-PCR after 2month, and evaluate its targets gens and functions with the help of bioinformatics and GO enrichment analysis respectively. RESULTS: Our results showed that simvastatin can increase miR-150-5p and therefore down regulate expression of its target genes involving in immune stimulation and decrease lipid profile including LDL-C, total cholesterol, and ApoB, especially in the group with type 2 diabetes mellitus (T2DM) and COVID-19 compared to the patients with only COVID-19. CONCLUSION: Simvastatin as an anti-inflammatory agent can modulate miRNAs expression; it can be suggested as an adjunct therapy especially for T2DM patients with COVID-19. Further studies may help us for developing better treatments about therapeutic manipulation of miRNAs in vivo.

Exosomal noncoding RNAs in colorectal cancer: An overview of functions, challenges, opportunities, and clinical applications.

Colorectal cancer (CRC) is the third most threatening malignancy worldwide. Colorectal tumors transfer information with their tumor microenvironment (TME) and communicate together which can be detected through exosome transmission. Exosomes are important regulators made by different types of cells in all body fluids containing RNA, DNA, metabolites, and proteins. Recently, Exosome-derived noncoding RNAs (ncRNAs) applications have gained great consideration based on their potential role in the different pathological processes. Therefore, in this review, we summarized the recent discoveries on exosomal ncRNAs function in CRC initiation and development, and drug resistance to provide a novel insight into exosomal ncRNAs' clinical application and their potential to be biomarkers for CRC patients.

The inhibitory role of stigmasterol on tumor growth by inducing apoptosis in Balb/c mouse with spontaneous breast tumor (SMMT).

BACKGROUND: Breast cancer is one of the most common types of cancer in women worldwide. Anti-apoptotic activity of cancer cells is considered the main reason for drug resistance in BC which reduces the 5-year survival rate of patients and is still considered the main obstacle for cancer therapy. Stigmasterol (SS) is natural phytosterols compound in the plant which has been proved to play an important role to lower cholesterol and inducing anti-inflammatory, and anticancer properties. METHODS: In this, study, we aimed to evaluate the effect of SS on the expression of anti-apoptotic genes (Bcl-2 and BCL-XL), and also evaluate its effects on cell apoptosis and cell viability using MCF-7 cell line as well as evaluating its effect on tumor growth of spontaneous breast tumor (SMMT) in vivo. RESULT: SS significantly decreased the expression of Bcl-2 and BCL-XL genes (*P < 0.05), induced apoptosis, and reduced cell proliferation in MCF-7 cell lines. Our in vivo study also indicated that SS could inhibit tumor size after treatment with (0, 10, 20 µM) compared to the normal control. CONCLUSION: SS can be suggested as a potential agent in BC cancer treatment or as an adjuvant based on its ability to decrease the expression of Bcl-2 and BCL-XL genes and induce apoptosis.

piRNAs and PIWI proteins as potential biomarkers in |Breast cancer.

BACKGROUND: PIWI interacting RNAs (piRNAs) are another subgroup of small non-coding RNAs, that can play different biological activity further to their capabilities in the germline such as regulating the gene and protein expression, epigenetic silencing of transposable elements, and regulating the spermatogenesis by interacting with PIWI proteins. METHODS: We search online academic data bases including (Google Scholar, Web of Science and Pub Med), the relevant literature was extracted from the databases by using search terms of piRNAs and breast cancer  as free-text words and also with the combination with OR /AND by may 2022. RESULTS: Recently, with the help of next-generation sequencing abnormal piRNA expression has been observed to associate with the occurrence and development of human cancers, such as  breast cancer (BC). Recent investigation proposing piRNA as a prognostic and diagnostic biomarker based on their cancer-related interaction in the treatment of BC. CONCLUSION: This review aims to focus on the role of piRNAs in the initiation, progression, and the occurrence of breast cancer in order to understand its function and provide a better therapeutic strategy.

Circular RNA circ_0051620 sponges miR-338-3p and regulates ADAM17 to promote the gastric cancer progression.

BACKGROUND: Gastric cancer (GC) is the fifth most common threatening cancer-related death globally. Recent studies indicate that circRNAs play a critical role in various biological and pathogenesis processes, including proliferation, apoptosis, and invasion of GC through sponging different miRNAs. However, the in-depth investigations of circRNAs in the progression of GC remains unclear, therefore in the current study, we aimed to investigate the mechanism behind the circular RNA circ_0051620 in the progression of GC through spooning the miR-338-3p and ADAM17. METHODS: At first, circRNA microarray was used to identify the expression profiles of circRNA in GC tissues. Further, qRT-PCR was performed to detect genes expression. Then, the clinical significance of circ_0051620 was evaluated. Afterward, bioinformatical database, dual-luciferase reporter assays were used to determine the regulatory networks of circ_0051620 and miR-338-3p in GC cells respectively. The Transwell experiments were used to explore the effects of circ_0051620, miR-338-3p, ADAM17 on the migration and invasion of GC cells. RESULTS: qRT-PCR results indicated that circ_0051620 in GC was over-expressed in tumoral tissues and cell lines compared to the normal controls. Moreover, miR-338-3p was confirmed to be the target of circ_0051620. Overall overexpression of miR-338-3p inhibited the cell migration, invasion through inhibiting ADAM17 in GC cells. CONCLUSION: The overexpression of circ_0051620 is found to be associated with progress and poor prognosis of GC, promoting the development and metastasis via sponging miR-338-3p and decoying ADAM17.

The function of novel small non-coding RNAs (piRNAs, tRFs) and PIWI protein in colorectal cancer.

Although great research has been done to clarify the pathogenesis of colorectal cancer (CRC), it is still the third common cancer worldwide. Pathogenesis of CRC as a heterogeneous disease is correlated with mutations and epigenetic alterations that result in the inactivation of tumor-suppressive and activation of an oncogene. Small non-coding RNAs (sncRNAs), emerging as a key player in regulating the genes and protein expression, with a length less than 200 nucleotide (nt). In this review, we aimed to focus on the role and the biogenesis of PIWI-interacting RNA (piRNAs), and tRNA-derived small RNA (tRFs) and PIWI proteins in the initiation, progression, and metastasis of CRC and their molecular mechanisms to understand their function in cancers and to provide better therapeutic strategies for CRC.