Overview of the role and action mechanism of microRNA-128 in viral infections.

Recently in vivo and in vitro studies have provided evidence establishing the significance of microRNAs (miRNAs) in both physiological and pathological conditions. In this regard, the role of miRNA-128 (miR-128) in health and diseases has been found, and its critical regulatory role in the context of some viral diseases has been recently identified. For instance, it has been found that miR-128 can serve as an antiviral mediator and significantly limit the replication and dissemination of human immunodeficiency virus type 1 (HIV-1). Besides, it has been noted that poliovirus receptor-related 4 (PVRL4) is post-transcriptionally regulated by miR-128, representing possible miRNA targets that can modulate measles virus infection. Of note, the downregulation of seminal exosomes eca-miR-128 is associated with the long-term persistence of Equine arteritis virus (EAV) in the reproductive tract, and this particular miRNA is a putative regulator of chemokine ligand 16 (C-X-C motif) as determined by target prediction analysis. In this review, the latest information on the role and action mechanism of miR-128 in viral infections will be summarized and discussed in detail.

Emerging role of microbiota derived outer membrane vesicles to preventive, therapeutic and diagnostic proposes.

The role of gut microbiota and its products in human health and disease is profoundly investigated. The communication between gut microbiota and the host involves a complicated network of signaling pathways via biologically active molecules generated by intestinal microbiota. Some of these molecules could be assembled within nanoparticles known as outer membrane vesicles (OMVs). Recent studies propose that OMVs play a critical role in shaping immune responses, including homeostasis and acute inflammatory responses. Moreover, these OMVs have an immense capacity to be applied in medical research, such as OMV-based vaccines and drug delivery. This review presents a comprehensive overview of emerging knowledge about biogenesis, the role, and application of these bacterial-derived OMVs, including OMV-based vaccines, OMV adjuvants characteristics, OMV vehicles (in conjugated vaccines), cancer immunotherapy, and drug carriers and delivery systems. Moreover, we also highlight the significance of the potential role of these OMVs in diagnosis and therapy.

The potential importance of autophagy genes expression profile dysregulation and ATG polymorphisms in COVID-19 pathogenesis.

Autophagy is one of the important mechanisms in cell maintenance, which is considered associated with different pathological conditions such as viral infections. In this current study, the expression level and polymorphisms in some of the most important genes in the autophagy flux in COVID-19 patients were evaluated. This cross-sectional study was conducted among 50 confirmed COVID-19 patients and 20 healthy controls. The COVID-19 patients were divided into a severe group and a mild group according to their clinical features. The expression levels of ATG5, ATG16L1, LC3, and BECN1 were evaluated by the 2-∆∆CT method and beta-actin as the internal control. The polymorphisms of the ATG5 (rs506027, rs510432) and ATG16L1 (rs2241880 or T300A) were evaluated by the Sanger sequencing following the conventional PCR. The mean age of the included patients was 58.3 ± 17.9 and 22 (44%) were female. The expression levels of the LC3 were downregulated, while BECN1 and ATG16L1 genes represent an upregulation in COVID-19 patients. The polymorphism analysis revealed the ATG16L1 rs2241880 and AGT5 rs506027 polymorphism frequencies are statistically significantly different between COVID-19 and Healthy controls. The autophagy alteration represents an association with COVID-19 pathogenesis and severity. The current study is consistent with the alteration of autophagy elements in COVID-19 patients by mRNA expression-level evaluation. Furthermore, ATG16L1 rs2241880 and AGT5 rs506027 polymorphisms seem to be important in COVID-19 and are highly suggested for further investigations.

The functions and molecular mechanisms of Tribbles homolog 3 (TRIB3) implicated in the pathophysiology of cancer.

Currently, cancer ranks as the second leading cause of death worldwide, and at the same time, the burden of cancer continues to increase. The underlying molecular pathways involved in the initiation and development of cancer are the subject of considerable research worldwide. Further understanding of these pathways may lead to new cancer treatments. Growing data suggest that Tribble's homolog 3 (TRIB3) is essential in oncogenesis in many types of cancer. The mammalian tribbles family's proteins regulate various cellular and physiological functions, such as the cell cycle, stress response, signal transduction, propagation, development, differentiation, immunity, inflammatory processes, and metabolism. To exert their activities, Tribbles proteins must alter key signaling pathways, including the mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3 kinase (PI3K)/AKT pathways. Recent evidence supports that TRIB3 dysregulation has been linked to various diseases, including tumor development and chemoresistance. It has been speculated that TRIB3 may either promote or inhibit the onset and development of cancer. However, it is still unclear how TRIB3 performs this dual function in cancer. In this review, we present and discuss the most recent data on the role of TRIB3 in cancer pathophysiology and chemoresistance. Furthermore, we describe in detail the molecular mechanism TRIB3 regulates in cancer.

The potential importance of autophagy genes expression profile dysregulation and ATG polymorphisms in COVID-19 pathogenesis.

Autophagy is one of the important mechanisms in cell maintenance, which is considered associated with different pathological conditions such as viral infections. In this current study, the expression level and polymorphisms in some of the most important genes in the autophagy flux in COVID-19 patients were evaluated. This cross-sectional study was conducted among 50 confirmed COVID-19 patients and 20 healthy controls. The COVID-19 patients were divided into a severe group and a mild group according to their clinical features. The expression levels of ATG5, ATG16L1, LC3, and BECN1 were evaluated by the 2-∆∆CT method and beta-actin as the internal control. The polymorphisms of the ATG5 (rs506027, rs510432) and ATG16L1 (rs2241880 or T300A) were evaluated by the Sanger sequencing following the conventional PCR. The mean age of the included patients was 58.3 ± 17.9 and 22 (44%) were female. The expression levels of the LC3 were downregulated, while BECN1 and ATG16L1 genes represent an upregulation in COVID-19 patients. The polymorphism analysis revealed the ATG16L1 rs2241880 and AGT5 rs506027 polymorphism frequencies are statistically significantly different between COVID-19 and Healthy controls. The autophagy alteration represents an association with COVID-19 pathogenesis and severity. The current study is consistent with the alteration of autophagy elements in COVID-19 patients by mRNA expression-level evaluation. Furthermore, ATG16L1 rs2241880 and AGT5 rs506027 polymorphisms seem to be important in COVID-19 and are highly suggested for further investigations.

The role of miRNA-128 in the development and progression of gastrointestinal and urogenital cancer.

Increasing data have shown the significance of various miRNAs in malignancy. In this regard, parallel to its biological role in normal tissues, miRNA-128 (miR-128) has been found to play an essential immunomodulatory function in the process of cancer initiation and development. The occurrence of the aberrant expression of miR-128 in tumors and the unique properties of miRNAs raise the prospect of their use as biomarkers and the next generation of molecular anticancer therapies. The function of miR-128 in malignancies such as breast, prostate, colorectal, gastric, pancreatic, esophageal, cervical, ovarian and bladder cancers and hepatocellular carcinoma is discussed in this review. Finally, the effect of exosomal miR-128 on cancer resistance to therapeutics and cancer immunotherapy in certain malignancies is highlighted.

Metabolic reprogramming by miRNAs in the tumor microenvironment: Focused on immunometabolism.

MicroRNAs (miRNAs) are emerging as a significant modulator of immunity, and their abnormal expression/activity has been linked to numerous human disorders, such as cancer. It is now known that miRNAs potentially modulate the production of several metabolic processes in tumor-associated immune cells and indirectly via different metabolic enzymes that affect tumor-associated signaling cascades. For instance, Let-7 has been identified as a crucial modulator for the long-lasting survival of CD8+ T cells (naive phenotypes) in cancer by altering their metabolism. Furthermore, in T cells, it has been found that enhancer of zeste homolog 2 (EZH2) expression is controlled via glycolytic metabolism through miRNAs in patients with ovarian cancer. On the other hand, immunometabolism has shown us that cellular metabolic reactions and processes not only generate ATP and biosynthetic intermediates but also modulate the immune system and inflammatory processes. Based on recent studies, new and encouraging approaches to cancer involving the modification of miRNAs in immune cell metabolism are currently being investigated, providing insight into promising targets for therapeutic strategies based on the pivotal role of immunometabolism in cancer. Throughout this overview, we explore and describe the significance of miRNAs in cancer and immune cell metabolism.

The emerging microbiome-based approaches to IBD therapy: From SCFAs to urolithin A.

Inflammatory bowel disease (IBD) is a group of chronic gastrointestinal inflammatory conditions which can be life-threatening, affecting both children and adults. Crohn's disease and ulcerative colitis are the two main forms of IBD. The pathogenesis of IBD is complex and involves genetic background, environmental factors, alteration in gut microbiota, aberrant immune responses (innate and adaptive), and their interactions, all of which provide clues to the identification of innovative diagnostic or prognostic biomarkers and the development of novel treatments. Gut microbiota provide significant benefits to its host, most notably via maintaining immunological homeostasis. Furthermore, changes in gut microbial populations may promote immunological dysregulation, resulting in autoimmune diseases, including IBD. Investigating the interaction between gut microbiota and immune system of the host may lead to a better understanding of the pathophysiology of IBD as well as the development of innovative immune- or microbe-based therapeutics. In this review we summarized the most recent findings on innovative therapeutics for IBD, including microbiome-based therapies such as fecal microbiota transplantation, probiotics, live biotherapeutic products, short-chain fatty acids, bile acids, and urolithin A.

The emerging role of 27-hydroxycholesterol in cancer development and progression: An update.

Oxysterols are cholesterol metabolites generated in the liver and other peripheral tissues as a mechanism of removing excess cholesterol. Oxysterols have a wide range of biological functions, including the regulation of sphingolipid metabolism, platelet aggregation, and apoptosis. However, it has been found that metabolites derived from cholesterol play essential functions in cancer development and immunological suppression. In this regard, research indicates that 27-hydroxycholesterol (27-HC) might act as an estrogen, promoting the growth of estrogen receptor (ER) positive breast cancer cells. The capacity of cholesterol to dynamically modulate signaling molecules inside the membrane and particular metabolites serving as signaling molecules are two possible contributory processes. 27-HC is a significant metabolite produced mainly through the CYP27A1 (Cytochrome P450 27A1) enzyme. 27-HC maintains cholesterol balance biologically by promoting cholesterol efflux via the liver X receptor (LXR) and suppressing de novo cholesterol production through the Insulin-induced Genes (INSIGs). It has been demonstrated that 27-HC is able to function as a selective ER regulator. Moreover, enhanced 27-HC production is in favor of the growth of end-stage malignancies in the brain, thyroid organs, and colon, as shown in breast cancer, probably due to pro-survival and pro-inflammatory signaling induced by unbalanced levels of oxysterols. However, the actual role of 27-HC in cancer promotion and progression remains debatable, and many studies are warranted to be performed to unravel the precise function of these molecules. This review article will summarize the latest evidence on the deleterious or beneficial functions of 27-HC in various types of cancer, such as breast cancer, prostate cancer, colon cancer, gastric cancer, ovarian cancer, endometrial cancer, lung cancer, melanoma, glioblastoma, thyroid cancer, adrenocortical cancer, and hepatocellular carcinoma.

Eosinophilic granulomatosis with polyangiitis after COVID-19: A case report.

COVID-19 can damage the endothelial cells of every organ in the body and lead to vasculopathy and vasculitis. It has been shown that various types of vasculitis could be a new manifestation of COVID-19. Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare systemic necrotizing vasculitis that affects small vessels. Here we report our experience with a 42-year-old man with a 3-weeks history of fever of unknown origin after two months from COVID-19 recovery presented with loss of appetite, loss of weight, and paresthesia in his lower extremities. After required evaluations including nerve biopsy, EGPA was diagnosed for him.

The deciphering of the immune cells and marker signature in COVID-19 pathogenesis: An update.

The precise interaction between the immune system and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical in deciphering the pathogenesis of coronavirus disease 2019 (COVID-19) and is also vital for developing novel therapeutic tools, including monoclonal antibodies, antivirals drugs, and vaccines. Viral infections need innate and adaptive immune reactions since the various immune components, such as neutrophils, macrophages, CD4+ T, CD8+ T, and B lymphocytes, play different roles in various infections. Consequently, the characterization of innate and adaptive immune reactions toward SARS-CoV-2 is crucial for defining the pathogenicity of COVID-19. In this study, we explain what is currently understood concerning the conventional immune reactions to SARS-CoV-2 infection to shed light on the protective and pathogenic role of immune response in this case. Also, in particular, we investigate the in-depth roles of other immune mediators, including neutrophil elastase, serum amyloid A, and syndecan, in the immunopathogenesis of COVID-19.

The emerging role of microbiota-derived short-chain fatty acids in immunometabolism.

The accumulating evidence revealed that microbiota plays a significant function in training, function, and the induction of host immunity. Once this interaction (immune system-microbiota) works correctly, it enables the production of protective responses against pathogens and keeps the regulatory pathways essential for maintaining tolerance to innocent antigens. This concept of immunity and metabolic activity redefines the realm of immunometabolism, paving the way for innovative therapeutic interventions to modulate immune cells through immune metabolic alterations. A body of evidence suggests that microbiota-derived metabolites, including short-chain fatty acids (SCFAs) such as butyrate, acetate, and propionate, play a key role in immune balance. SCFAs act on many cell types to regulate various vital biological processes, including host metabolism, intestinal function, and the immune system. Such SCFAs generated by gut bacteria also impact immunity, cellular function, and immune cell fate. This is a new concept of immune metabolism, and better knowledge about how lifestyle affects intestinal immunometabolism is crucial for preventing and treating disease. In this review article, we explicitly focus on the function of SCFAs in the metabolism of immune cells, especially macrophages, neutrophils, dendritic cells (DCs), B cells, T (Th) helper cells, and cytotoxic T cells (CTLs).

Coronavirus disease 2019 (COVID-19) update: From metabolic reprogramming to immunometabolism.

The field of immunometabolism investigates and describes the effects of metabolic rewiring in immune cells throughout activation and the fates of these cells. Recently, it has been appreciated that immunometabolism plays an essential role in the progression of viral infections, cancer, and autoimmune diseases. Regarding COVID-19, the aberrant immune response underlying the progression of diseases establishes two major respiratory pathologies, including acute respiratory distress syndrome (ARDS) or pneumonia-induced acute lung injury (ALI). Both innate and adaptive immunity (T cell-based) were impaired in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Current findings have deciphered that macrophages (innate immune cells) are involved in the inflammatory response seen in COVID-19. It has been demonstrated that immune system cells can change metabolic reprogramming in some conditions, including autoimmune diseases, cancer, and infectious disease, including COVID-19. The growing findings on metabolic reprogramming in COVID-19 allow an exploration of metabolites with immunomodulatory properties as future therapies to combat this hyperinflammatory response. The elucidation of the exact role and mechanism underlying this metabolic reprograming in immune cells could help apply more precise approaches to initial diagnosis, prognosis, and in-hospital therapy. This report discusses the latest findings from COVID-19 on host metabolic reprogramming and immunometabolic responses.

Angioregulatory role of miRNAs and exosomal miRNAs in glioblastoma pathogenesis.

Glioblastoma (GB) is a highly aggressive cancer of the central nervous system, occurring in the brain or spinal cord. Many factors such as angiogenesis are associated with GB development. Angiogenesis is a procedure by which the pre-existing blood vessels create new vessels that play an essential role in health and disease, including tumors. Also, angiogenesis is one of the significant factors thought to be responsible for treatment resistance in many tumors, including GB. Hence, an improved understanding of the molecular processes underlying GB angiogenesis will pave the way for developing potential new treatments. Recently, it has been found that microRNAs (miRNAs) and exosomal miRNAs have a crucial role in inducing or inhibiting the angiogenesis process in GB development. A better knowledge of the miRNA's regulation pathway in the angiogenesis process in cancer offers unique mechanistic insight into the mechanism of tumor-associated neovascularization. Because of advancements in miRNA characterization and delivery methods, miRNAs can also be employed in clinical settings as potential biomarkers for anti-angiogenic treatment response as well as therapies targeting tumor angiogenesis. The recent finding and insights about miRNAs' angioregulatory role and exosomal miRNAs in GB are provided throughout the review. Also, we discuss the new concept of miRNAs-based therapies for GB in the future.

Immunometabolism in biofilm infection: lessons from cancer.

BACKGROUND: Biofilm is a community of bacteria embedded in an extracellular matrix, which can colonize different human cells and tissues and subvert the host immune reactions by preventing immune detection and polarizing the immune reactions towards an anti-inflammatory state, promoting the persistence of biofilm-embedded bacteria in the host. MAIN BODY OF THE MANUSCRIPT: It is now well established that the function of immune cells is ultimately mediated by cellular metabolism. The immune cells are stimulated to regulate their immune functions upon sensing danger signals. Recent studies have determined that immune cells often display distinct metabolic alterations that impair their immune responses when triggered. Such metabolic reprogramming and its physiological implications are well established in cancer situations. In bacterial infections, immuno-metabolic evaluations have primarily focused on macrophages and neutrophils in the planktonic growth mode. CONCLUSION: Based on differences in inflammatory reactions of macrophages and neutrophils in planktonic- versus biofilm-associated bacterial infections, studies must also consider the metabolic functions of immune cells against biofilm infections. The profound characterization of the metabolic and immune cell reactions could offer exciting novel targets for antibiofilm therapy.

Dual role of microbiota-derived short-chain fatty acids on host and pathogen.

A growing body of documents shows microbiota produce metabolites such as short-chain fatty acids (SCFAs) as crucial executors of diet-based microbial influence the host and bacterial pathogens. The production of SCFAs depends on the metabolic activity of intestinal microflora and is also affected by dietary changes. SCFAs play important roles in maintaining colonic health as an energy source, as a regulator of gene expression and cell differentiation, and as an anti-inflammatory agent. Additionally, the regulated expression of virulence genes is critical for successful infection by an intestinal pathogen. Bacteria rely on sensing environmental signals to find preferable niches and reach the infectious state. This review will present data supporting the diverse functional roles of microbiota-derived butyrate, propionate, and acetate on host cellular activities such as immune modulation, energy metabolism, nervous system, inflammation, cellular differentiation, and anti-tumor effects, among others. On the other hand, we will discuss and summarize data about the role of these SCFAs on the virulence factor of bacterial pathogens. In this regard, receptors and signaling routes for SCFAs metabolites in host and pathogens will be introduced.

Pathogenic role of 25-hydroxycholesterol in cancer development and progression.

Cholesterol is an essential lipid that serves several important functions, including maintaining the homeostasis of cells, acting as a precursor to bile acid and steroid hormones and preserving the stability of membrane lipid rafts. 25-hydroxycholesterol (25-HC) is a cholesterol derivative that may be formed from cholesterol. 25-HC is a crucial component in various biological activities, including cholesterol metabolism. In recent years, growing evidence has shown that 25-HC performs a critical function in the etiology of cancer, infectious diseases and autoimmune disorders. This review will summarize the latest findings regarding 25-HC, including its biogenesis, immunomodulatory properties and role in innate/adaptive immunity, inflammation and the development of various types of cancer.

The role of miR-128 in cancer development, prevention, drug resistance, and immunotherapy.

A growing body of evidence has revealed that microRNA (miRNA) expression is dysregulated in cancer, and they can act as either oncogenes or suppressors under certain conditions. Furthermore, some studies have discovered that miRNAs play a role in cancer cell drug resistance by targeting drug-resistance-related genes or influencing genes involved in cell proliferation, cell cycle, and apoptosis. In this regard, the abnormal expression of miRNA-128 (miR-128) has been found in various human malignancies, and its verified target genes are essential in cancer-related processes, including apoptosis, cell propagation, and differentiation. This review will discuss the functions and processes of miR-128 in multiple cancer types. Furthermore, the possible involvement of miR-128 in cancer drug resistance and tumor immunotherapeutic will be addressed.