RESUMEN
BACKGROUND: Zika virus (ZIKV) stands as one of the most significant reemerging viral pathogens, linked to neurological diseases such as meningoencephalitis and congenital microcephaly. Today there are no effective therapies for treating ZIKV-infected patients. MiRNAs play a critical role in regulating cellular signaling and physiological conditions, and alterations in their profiles can bear great significance in disease progression. OBJECTIVES: Despite significant progress in understanding the interaction between the ZIKV and its host since the outbreak, a more comprehensive understanding on these interactions is imperative. This review aims to summarize the studies in the field and shed light on the intricate relationship between ZIKV and its host at the molecular level. CONTENT: We found that in ZIKV-infected humans, over-expression of miR-431-5p and miR-30e-5p plays a crucial role in innate immune responses and contributes to neurological damage. Additionally, in ZIKA-infected mice, we observed upregulated expression of all the targets of miR-124-3p including CCL2, IL7, IRF1, and SBNO2. Notably, other targets of this miRNA include TLR6, TNF, STAT3, and NF-kB also exhibited upregulation in the central nervous system (CNS) of infected mice. Conversely, miR-654-3p levels were reduced, correlating with the upregulation of its predicted targets including FLT3LG, LITAF, CD69, and TLR2. In the case of insects, aae-miR-286a/b-3p was predicted to target all ZIKV genotypes. This specific miRNA is typically found in ovaries and can be transferred to embryos. In conclusion, our findings suggest that host microRNAs and ZIKV-encoded microRNAs hold promise as potential targets for the diagnosis of ZIKV infections and may even serve as a therapeutic approach for managing this infectious disease.
RESUMEN
Systemic lupus erythematosus (SLE), an autoimmune disease, is among the most prevalent rheumatic autoimmune disorders. It affects autologous connective tissues caused by the breakdown of self-tolerance mechanisms. During the last two decades, stem cell therapy has been increasingly considered as a therapeutic option in various diseases, including parkinson's disease, alzheimer, stroke, spinal cord injury, multiple sclerosis, inflammatory bowel disease, liver disease, diabete, heart disease, bone disease, renal disease, respiratory diseases, and hematological abnormalities such as anemia. This is due to the unique properties of stem cells that divide and differentiate to the specialized cells in the damaged tissues. Moreover, they impose immunomodulatory properties affecting the diseases caused by immunological abnormalities such as rheumatic autoimmune disorders. In the present manuscript, efficacy of stem cell therapy with two main types of stem cells, including mesenchymal stem cell (MSC), and hematopoietic stem cells (HSC) in animal models or human patients of SLE, has been reviewed. Taken together, MSC and HSC therapies improved the disease activity, and severity in kidney, lung, liver, and bone (improvement in the clinical manifestation). In addition, a change in the immunological parameters occurred (improvement in immunological parameters). The level of autoantibodies, including antinuclear antibody (ANA), and anti-double-stranded deoxyribonucleic acid antibodies (dsDNA Abs) reduced. A conversion of Th1/Th2 ratio (in favor of Th2), and Th17/Treg (in favor of Treg) was also detected. In spite of many advantages of MSC and HSC transplantations, including efficacy, safety, and increased survival rate of SLE patients, some complications, including recurrence of the disease, occurrence of infections, and secondary autoimmune diseases (SAD) were observed after transplantation that should be addressed in the next studies.
RESUMEN
Helicobacter pylori (H. pylori) is one of the most prevalent human pathogens and the leading cause of chronic infection in almost half of the population in the world (~59%). The bacterium is a major leading cause of chronic gastritis, gastric and duodenal ulcers, and two type of malignancies, gastric adenocarcinoma and mucosa-associated lymphoid tissue (MALT) lymphoma. Despite the immune responses mounted by the host, the bacteria are not cleared from the body resulting in a chronic infection accompanied by a chronic inflammation. Herein, a review of the literature discussing H. pylori antigens modulating the immune responses is presented. The mechanisms that are involved in the modulation of innate immune response, include modulation of recognition by pattern recognition receptors (PRRs) such as modulation of recognition by toll like receptors (TLR)4 and TLR5, modulation of phagocytic function, and modulation of phagocytic killing mediated by reactive oxygen species (ROS) and nitric oxide (NO). On the other hands, H. pylori modulates acquired immune response by the induction of tolerogenic dendritic cells (DCs), modulation of apoptosis, induction of regulatory T cells, modulation of T helper (Th)1 response, and modulation of Th17 response.
Asunto(s)
Gastritis , Infecciones por Helicobacter , Helicobacter pylori , Humanos , Gastritis/microbiología , Infección Persistente , Infecciones por Helicobacter/microbiología , Sistema Inmunológico/patología , Antígenos Bacterianos , Factores Inmunológicos , Mucosa Gástrica/microbiologíaRESUMEN
BACKGROUND: The COVID-19 pandemic has had a profound global impact, with variations in susceptibility, severity, and mortality rates across different regions. While many factors can contribute to the spread and impact of the disease, specifically human leukocyte antigen (HLA) genetic variants have emerged as potential contributors to COVID-19 outcomes. METHODS: In this comprehensive narrative review, we conducted a thorough literature search to identify relevant studies investigating the association between HLA genetic variants and COVID-19 outcomes. Additionally, we analyzed allelic frequency data from diverse populations to assess differences in COVID-19 incidence and severity. RESULTS: Our review provides insights into the immunological mechanisms involving HLA-mediated responses to COVID-19 and highlights potential research directions and therapeutic interventions. We found evidence suggesting that certain HLA alleles, such as HLA-A02, may confer a lower risk of COVID-19, while others, like HLA-C04, may increase the risk of severe symptoms and mortality. Furthermore, our analysis of allele frequency distributions revealed significant variations among different populations. CONCLUSION: Considering host genetic variations, particularly HLA genetic variants, is crucial for understanding COVID-19 susceptibility and severity. These findings have implications for personalized treatment and interventions based on an individual's genetic profile. However, further research is needed to unravel the precise mechanisms underlying the observed associations and explore the potential for targeted therapies or preventive measures based on HLA genetic variants.
Asunto(s)
COVID-19 , Humanos , COVID-19/genética , SARS-CoV-2/genética , Pandemias , Frecuencia de los Genes/genéticaRESUMEN
Autoimmune diseases, including SSc, are prevalent, affecting autologous connective tissues and caused by the breakdown of self-tolerance mechanisms of the immune system. During the last 2 decades, stem cell therapy has been increasingly considered as a therapeutic option in various diseases, including Parkinson's disease, Alzheimer's disease, stroke, spinal cord injury, multiple sclerosis, inflammatory bowel disease, liver disease, diabetes, heart disease, bone disease, renal disease, respiratory disease and haematological abnormalities such as anaemia. This is due to the unique properties of stem cells that both divide and differentiate to the specialized cells in the damaged tissue. Moreover, they impose immunomodulatory properties affecting the diseases caused by immunological abnormalities such as SSc. In the present review, the efficacy of stem cell therapy with two main types of stem cells, including mesenchymal stem cells and hematopoietic stem cells, will be reviewed. Moreover, other related issues, including safety, changes in immunological parameters, suitable choice of stem cell origin, conditioning regimen and complications of stem cell treatment will be discussed.
RESUMEN
Autoimmune diseases, including rheumatoid arthritis that is the most prevalent rheumatic autoimmune disorder, affect autologous connective tissues caused by the breakdown of the self-tolerance mechanisms of the immune system. During the last two decades, cell-based therapy, including stem cells and none-stem cells has been increasingly considered as a therapeutic option in various diseases. This is partly due to the unique properties of stem cells that divide and differentiate from the specialized cells in the damaged tissue. Moreover, stem cells and none-stem cells, impose immunomodulatory properties affecting the diseases caused by immunological abnormalities such as rheumatic autoimmune disorders. In the present review, the efficacy of cell-based therapy with four main types of stem cells, including mesenchymal stem cells, hematopoietic stem cells, embryonic stem cells, and human amniotic membrane cells, as well as none-stem cells, including regulatory T cells, chimeric antigen receptor T cells, and tolerogenic dendritic cells will be evaluated. Moreover, other related issues, including safety, changes in immunological parameters, suitable choice of stem cell and none-stem cell origin, conditioning regimen, limitations, and complications will be discussed.
Asunto(s)
Artritis Reumatoide , Enfermedades Autoinmunes , Células Madre Mesenquimatosas , Humanos , Artritis Reumatoide/terapia , Tolerancia Inmunológica , InmunomodulaciónRESUMEN
Systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and systemic sclerosis (SSc) are the most common rheumatic autoimmune diseases/disorders (RADs) that affect autologous connective tissues as a result of the breakdown of the self-tolerance mechanisms of the immune system. Prolactin, a glycoprotein hormone, has been known for its crucial role in the pathogenesis of these rheumatic autoimmune diseases. In addition to regulating lymphocyte proliferation and antibody synthesis, prolactin is also responsible for regulating cytokine production. Moreover, it contributes to the breakdown of central and peripheral tolerance mechanisms of B lymphocytes. Given the crucial role of prolactin in the pathogenesis of the mentioned RADs, prolactin may contribute to their pathogenesis by the breakdown of tolerance. In the present study, the key role of prolactin to the breakdown of B lymphocyte tolerance and its possible implication for the pathogenesis of these diseases is discussed. Current literature supports prolactin's role in the breakdown of B lymphocyte central and peripheral tolerance mechanisms, such apoptosis, receptor editing, and also anergy. Therefore, prolactin may contribute to the pathogenesis of RADs by the breakdown of B lymphocyte tolerance. However, more investigations, particularly in RA and SSc animal models, are required to precisely address the pathologic role of prolactin.
RESUMEN
Evidence demonstrates that T cells are implicated in developing SLE, and each of them dominantly uses distinct metabolic pathways. Indeed, intracellular enzymes and availability of specific nutrients orchestrate fate of T cells and lead to differentiation of regulatory T cells (Treg), memory T cells, helper T cells, and effector T cells. The function of T cells in inflammatory and autoimmune responses is determined by metabolic processes and activity of their enzymes. Several studies were conducted to determine metabolic abnormalities in SLE patients and clarify how these modifications could control the functions of the involved T cells. Metabolic pathways such as glycolysis, mitochondrial pathways, oxidative stress, mTOR pathway, fatty acid and amino acid metabolisms are dysregulated in SLE T cells. Moreover, immunosuppressive drugs used in treating autoimmune diseases, including SLE, could affect immunometabolism. Developing drugs to regulate autoreactive T cell metabolism could be a promising therapeutic approach for SLE treatment. Accordingly, increased knowledge about metabolic processes paves the way to understanding SLE pathogenesis better and introduces novel therapeutic options for SLE treatment. Although monotherapy with metabolic pathways modulators might not be sufficient to prevent autoimmune disease, they may be an ideal adjuvant to reduce administration doses of immunosuppressive drugs, thus reducing drug-associated adverse effects. This review summarized emerging data about T cells that are involved in SLE pathogenesis, focusing on immunometabolism dysregulation and how these modifications could affect the disease development.
Asunto(s)
Enfermedades Autoinmunes , Lupus Eritematoso Sistémico , Enfermedades de la Piel , Humanos , Linfocitos T Colaboradores-Inductores , Linfocitos T Reguladores , Estrés Oxidativo , InmunosupresoresRESUMEN
The infection caused by P. aeruginosa still is dangerous throughout the world. This is partly due to its immune escape mechanisms considerably increasing the bacterial survival in the host. By escape from recognition by TLRs, interference with complement system activation, phagocytosis inhibition, production of ROS, inhibition of NET production, interference with the generation of cytokines, inflammasome inhibition, reduced antigen presentation, interference with cellular and humoral immunity, and induction of apoptotic cell death and MDSc, P. aeruginosa breaks down the barriers of the immune system and causes lethal infections in the host. Recognition of other immune escape mechanisms of P. aeruginosa may provide a basis for the future treatment of the infection. This manuscript may provide new insights and information for the development of new strategies to combat P. aeruginosa infection. In the present manuscript, the escape mechanisms of P. aeruginosa against immune response would be reviewed.
Asunto(s)
Infecciones por Pseudomonas , Pseudomonas aeruginosa , Humanos , Infección Persistente , Inflamasomas/metabolismo , Citocinas/metabolismoRESUMEN
Three main inflammatory signaling pathways include nuclear factor-κB (NF-κB), Janus kinases/Signal transducer and activator of transcriptions (JAKs/STATs), and mitogen-activated protein kinases (MAPKs) play crucial roles in inducing, promoting, and regulating inflammatory responses in the immune system. Importantly, the breakdown of mechanisms that tightly regulate inflammatory signaling pathways can be the underlying cause of uncontrolled inflammatory responses and be associated with the generation and development of several inflammatory diseases. Hence, therapeutic strategies targeting inflammatory signaling pathways and their downstream components may promise to treat inflammatory diseases. Studies over the past two decades have provided important information on the polytrophic pharmacological and biochemical properties of berberine (BBR) as a naturally occurring compound, such as antioxidant, antitumor, antimicrobial, and antiinflammatory activates. Interestingly, the modulatory effects of BBR on inflammatory signaling cascades, which lead to the inhibition of inflammation, have been widely investigated in several in vitro and in vivo studies. For the first time, herein, this comprehensive review attempts to put together these studies and provide important insight into the modulatory effects of BBR on NF-κB, JAKs/STATs, and MAPKs signaling pathways in vitro in various types of immune cells and in vivo in several experimental inflammatory diseases. As the second achievement of this review, we also explore the therapeutic efficacy and antiinflammatory effects of BBR regarding its modulatory action.
Asunto(s)
Berberina , FN-kappa B , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Berberina/farmacología , Berberina/uso terapéutico , Sistema Inmunológico , FN-kappa B/metabolismo , Transducción de SeñalRESUMEN
Fibroblast-like synoviocytes (FLSs) produce lots of inflammatory molecules that trigger immune responses and intensification the inflammation and thereby play important roles in Rheumatoid Arthritis )RA( pathogenesis. Due to the important roles of toll-like receptor 4 (TLR4) in cytokine production and inflammation, we aimed to evaluate the effects of TAK-242 (Resatorvid) on interleukin (IL)1-ß, IL-6, TNF-α, and TLR4 expression and two important proteins of nuclear factor-κB (NF-κB) signaling pathway (Ikßα and pIkßα) in RA and trauma FLSs. FLSs were isolated from synovial tissues of trauma (n=10) and RA (n=10) patients and cultured in Dulbecco's Modified Eagle Medium (DMEM). 3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide (MTT) was performed to evaluate the cytotoxicity effects of TAK-242 on the RA FLSs. Real-time PCR was performed to measure the expression level of IL1-ß, IL-6, TNF-α, and TLR4 genes in Lipopolysaccharide (LPS) and TAK-242 treated FLSs. Furthermore, the treated FLSs were evaluated for protein levels of Ikßα and pIkßα by western blot. The baseline expression of IL1-ß, IL-6, TNF-α, and TLR4 showed no significant differences between healthy and RA FLSs. LPS stimulated FLSs significantly increased mRNA levels of IL-1ß, IL-6, TNF-α, and TLR4 genes in both the healthy and RA FLSs compared with that of their control groups, and pretreatment with TAK-242 reversed the effect. Furthermore, LPS-stimulated FLSs significantly increased the level of pIkßα in both the healthy and RA FLSs compared with that of their control groups, and pretreatment with TAK-242 reversed the effect. We provide the data that TAK-242 through inhibiting the NF-κB signaling pathway may modulate TLR4-mediated inflammatory responses and could be considered as a potential therapeutic agent for RA patients.
Asunto(s)
Antiinflamatorios/farmacología , Artritis Reumatoide/metabolismo , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Sulfonamidas/farmacología , Sinoviocitos/efectos de los fármacos , Sinoviocitos/metabolismo , Antiinflamatorios/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/etiología , Artritis Reumatoide/patología , Biomarcadores , Células Cultivadas , Citocinas/genética , Citocinas/metabolismo , Susceptibilidad a Enfermedades , Regulación de la Expresión Génica , Humanos , Mediadores de Inflamación/metabolismo , FN-kappa B/metabolismo , Transducción de Señal , Sulfonamidas/uso terapéutico , Sinoviocitos/patologíaRESUMEN
Several studies have demonstrated that the genetic polymorphisms in the genes encoding immune regulatory molecules, namely cytotoxic T-lymphocyte-associated protein 4 (CTLA4) and CD28, play a fundamental role in susceptibility to rheumatoid arthritis (RA). Several disperse population studies have resulted in conflicting outcomes regarding the genetic polymorphisms in these genes and RA risk. This systematic review and meta-analysis study was performed to reach a conclusive understanding of the role of single-nucleotide polymorphisms (SNPs) of CTLA4-rs231775, CTLA4-rs5742909, and CD28-rs1980422 in susceptibility to RA. Databases (ISI Web of Science, MEDLINE/PubMed, and Scopus) were searched to find the case-control studies surveying the association of CTLA4 gene rs231775, CTLA4 gene rs5742909, and CD28 gene rs1980422 polymorphisms and RA susceptibility in different population until August 2020. Association comparison between the polymorphisms and RA proneness was assessed using pooled odds ratio (OR) and their corresponding 95% confidence interval. This study was conducted on 16 population studies, comprising 1078 RA patients and 1118 healthy controls for CTLA4-rs231775, 2193 RA patients and 2580 healthy controls for CTLA4-rs5742909, and 807 RA patients and 732 healthy controls for CD28-rs1980422. Analysis indicated that G-allele, GG and GA genotypes, and dominant model for rs231775, recessive model for rs5742909, and C-allele, CC and CT genotypes, and recessive model for rs1980422 were significantly associated with increased RA risk. This meta-analysis showed that genetic polymorphisms of both immune inhibitory and activating genes, including CTLA4-rs231775, CTLA4-rs5742909, and CD28-rs1980422 polymorphisms, may increase susceptibility to RA.
RESUMEN
Fibroblast-like synoviocytes (FLSs) have been introduced in recent years as a key player in the pathogenesis of rheumatoid arthritis (RA), but the exact mechanisms of their transformation and intracellular pathways have not yet been determined. This study aimed to investigate the role of fibroblast activation protein-alpha (FAP-α) in the regulation of genes involved in the transformation and pathogenic activity of RA FLSs. Synovial FLSs were isolated from RA patients and non-arthritic individuals (n=10 in both groups) and characterized; using immunocytochemistry and flow cytometry analysis. FLSs were divided into un-treated and Talabostat-treated groups to evaluate the FAP-α effect on the selected genes involved in cell cycle regulation (p21, p53, CCND1), apoptosis (Bcl-2, PUMA), and inflammatory and destructive behavior of FLSs (IL-6, TGF-ß1, MMP-2, MMP-9, P2RX7). Gene expression analysis was performed by quantitative real-time polymerase chain reaction (qRT-PCR), and immunoblotting was carried out to evaluate FAP-α protein levels. The basal level of FAP-α protein in RA patients was significantly higher than non-arthritic control individuals. However, no differences were observed between RA and non-arthritic FLSs, at the baseline mRNA levels of all the genes. Talabostat treatment significantly reduced FAP-α protein levels in both RA and non-arthritic FLSs, however, had no effect on mRNA expressions except an upregulated TGF-ß1 expression in non-arthritic FLSs. A significantly higher protein level of FAP-α in FLSs of RA patients compared with that of healthy individuals may point to the pathogenic role of this protein in RA FLSs. However, more investigations are necessary to address the mechanisms mediating the FAP-α pathogenic role in RA FLSs.
Asunto(s)
Artritis Reumatoide/metabolismo , Endopeptidasas/metabolismo , Fibroblastos/metabolismo , Proteínas de la Membrana/metabolismo , Sinoviocitos/metabolismo , Adulto , Anciano , Proteínas Reguladoras de la Apoptosis/genética , Proteínas Reguladoras de la Apoptosis/metabolismo , Artritis Reumatoide/genética , Artritis Reumatoide/patología , Estudios de Casos y Controles , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Células Cultivadas , Femenino , Fibroblastos/patología , Regulación de la Expresión Génica , Humanos , Mediadores de Inflamación/metabolismo , Masculino , Persona de Mediana Edad , Transducción de Señal , Sinoviocitos/patologíaRESUMEN
In the last two decades, we have witnessed three major epidemics of the coronavirus human disease namely, severe acute respiratory syndrome (SARS), Middle Eastern respiratory syndrome, and more recently an ongoing global pandemic of coronavirus disease 2019 (COVID-19). Iran, a country of nearly 84 million, in the Middle East, severely involved with the COVID-19 disease. A documented multidimensional approach to COVID-19 disease is therefore mandatory to provide a well-balanced platform for the concerned medical community in our county and beyond. In this review, we highlight the disease status in Iran and attempt to provide a multilateral view of the fundamental and clinical aspects of the disease including the clinical features of the confirmed cases, virology, pathogenesis, epidemiology, and laboratory methods needed for diagnosis.
RESUMEN
Swelling and the progressive destruction of articular cartilage are major characteristics of rheumatoid arthritis (RA), a systemic autoimmune disease that directly affects the synovial joints and often causes severe disability in the affected positions. Recent studies have shown that type B synoviocytes, which are also called fibroblast-like synoviocytes (FLSs), as the most commonly and chiefly resident cells, play a crucial role in early-onset and disease progression by producing various mediators. During the pathogenesis of RA, the FLSs' phenotype is altered, and represent invasive behavior similar to that observed in tumor conditions. Modified and stressful microenvironment by FLSs leads to the recruitment of other immune cells and, eventually, pannus formation. The origins of this cancerous phenotype stem fundamentally from the significant metabolic changes in glucose, lipids, and oxygen metabolism pathways. Moreover, the genetic abnormalities and epigenetic alterations have recently been implicated in cancer-like behaviors of RA FLSs. In this review, we will focus on the mechanisms underlying the transformation of FLSs to a cancer-like phenotype during RA. A comprehensive understanding of these mechanisms may lead to devising more effective and targeted treatment strategies.
RESUMEN
Generally, autoimmune diseases are more prevalent in females than males. Various predisposing factors, including female sex hormones, X chromosome genes, and the microbiome have been implicated in the female bias of autoimmune diseases. During embryogenesis, one of the X chromosomes in the females is transcriptionally inactivated, in a process called X chromosome inactivation (XCI). This equalizes the impact of two X chromosomes in the females. However, some genes escape from XCI, providing a basis for the dual expression dosage of the given gene in the females. In the present review, the contribution of the escape genes to the female bias of autoimmune diseases will be discussed.
Asunto(s)
Enfermedades Autoinmunes/etiología , Autoinmunidad/genética , Susceptibilidad a Enfermedades , Inactivación del Cromosoma X , Alelos , Animales , Enfermedades Autoinmunes/diagnóstico , Enfermedades Autoinmunes/metabolismo , Biomarcadores , Femenino , Expresión Génica , Regulación de la Expresión Génica , Genes Ligados a X , Humanos , Factores SexualesRESUMEN
BACKGROUND: Numerous investigations have previously evaluated the association of interleukin (IL) 4 gene polymorphisms and the risk of asthma, conferring inconsistent results. To resolve the incongruent outcomes yielded from different single studies, we conducted the most up-to-date meta-analysis of IL4 gene -589C/T (rs2243250) polymorphism and susceptibility to asthma. METHODS: A systematic literature search was performed in ISI web of science, Scopus, Medline/PubMed databases prior to September 2020, and the pooled odds ratio (OR) and their corresponding 95% CI were calculated to determine the association strength. RESULTS: Literature search led to retrieving of 49 publications (55 case-control studies) containing 9572 cases and 9881 controls. It was revealed that IL4 gene -589C/T polymorphism increased the risk of asthma across all genetic models, including dominant model (OR = 1.22), recessive model (OR = 1.17), allelic model (OR = 1.21), and TT vs. CC model (OR = 1.34), but not the CT vs. TT model. The subgroup analysis by age indicated that IL4 gene -589C/T polymorphism was significantly associated with asthma risk in both pediatrics and adults. Additionally, the subgroup analysis by ethnicity revealed significant association in Asian, American, and Europeans. Finally, subgroup analysis by East Asian and non-East Asian populations indicated significant associations. CONCLUSIONS: The current meta-analysis revealed that IL4 gene -589C/T polymorphism was a susceptibility risk in both pediatrics and adults in the whole and different ethnic groups.
Asunto(s)
Asma/genética , Genotipo , Interleucina-4/genética , Alelos , Estudios de Casos y Controles , Etnicidad , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Humanos , Polimorfismo de Nucleótido SimpleRESUMEN
Glucose metabolism is considerably increased in inflamed joints of rheumatoid arthritis (RA) patients at early stages. Fibroblast-like synoviocytes (FLSs) activation and subsequent joint damage are linked with metabolic alterations, especially glucose metabolism. It has been shown that glucose metabolism is elevated in aggressive phenotype of FLS cells. In this regard, glycolytic blockers are able to reduce aggressiveness of the FLS cells resulting in decreased joint damage in various arthritis models. Besides, metabolic changes in immune and non-immune cells such as FLS can provide important targets for therapeutic intervention. Glycolytic enzymes such as hexokinase 2 (HK2), phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB), and phosphoglycerate kinase (PGK) play essential roles in aggressive behavior of FLS cells. It has been documented that the HK2 enzyme is significantly upregulated in RA FLS cells, compared with osteoarthritis (OA) FLS cells. The HK2 is expressed in a few tissues and upregulated in the inflamed synovium of RA patients that makes it a potential target for RA treatment. Furthermore, HK2 has different roles in each cellular compartment, which offers another level of specificity and provides a specific target to reduce deleterious effects of inhibiting the enzyme in RA without affecting glycolysis in normal cells. Thus, targeting the HK2 enzyme might be an attractive potential selective target for arthritis therapy and safer than global glycolysis inhibition. Therefore, this review was aimed to summarize the current knowledge about glucose metabolism of FLS cells and suggest novel biomarkers, which are potential candidates for RA treatment.
Asunto(s)
Antiinflamatorios/farmacología , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/metabolismo , Glucosa/metabolismo , Sinoviocitos/efectos de los fármacos , Sinoviocitos/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , HumanosRESUMEN
BACKGROUND: A bulk of investigations imply that women with rheumatoid arthritis (RA) deliver fewer children in comparison to healthy women. PURPOSE: This review article attempts to clarify the involvement of infertility-related issues in both RA men and women. Moreover, the effect of RA disease on the fertility quality and quantity will be discussed. RESULTS: Declined fertility rate in RA women seems to stem from modified inflammatory settings, advanced maternal age, limited sexual activity, and adverse effects of drugs on ovarian function. Women with RA may have smaller families and seem to be slower to conceive relative to their peer women. The chance of gestation in RA women may drop due to suppressed sexual function through pain and fatigue. In addition, treatment of RA women with non-steroidal anti-inflammatory drugs (NSAIDs) may prevent ovulation and therefore hinder the conception. CONCLUSIONS: A complex interaction between RA disease and fertility related issues is present. Despite an increase rate of infertility in RA females or males, the mechanisms involved in this outcome is still unknown. Plausible causes of the decreased fertility rate in RA patients might be due to inflammatory cytokines, suppressed sexual activity, drug treatments, mother age, personal choice, or a combination of these elements.
Asunto(s)
Artritis Reumatoide/complicaciones , Fertilidad/fisiología , Infertilidad/epidemiología , Aborto Espontáneo/epidemiología , Antiinflamatorios no Esteroideos/efectos adversos , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/fisiopatología , Composición Familiar , Femenino , Humanos , Infertilidad/etiología , Masculino , Edad Materna , Preeclampsia/epidemiología , Embarazo , Inhibidores del Factor de Necrosis Tumoral/efectos adversosRESUMEN
Based on available metabolomic studies, influenza infection affects a variety of cellular metabolic pathways to ensure an optimal environment for its replication and production of viral particles. Following infection, glucose uptake and aerobic glycolysis increase in infected cells continually, which results in higher glucose consumption. The pentose phosphate shunt, as another glucose-consuming pathway, is enhanced by influenza infection to help produce more nucleotides, especially ATP. Regarding lipid species, following infection, levels of triglycerides, phospholipids, and several lipid derivatives undergo perturbations, some of which are associated with inflammatory responses. Also, mitochondrial fatty acid ß-oxidation decreases significantly simultaneously with an increase in biosynthesis of fatty acids and membrane lipids. Moreover, essential amino acids are demonstrated to decline in infected tissues due to the production of large amounts of viral and cellular proteins. Immune responses against influenza infection, on the other hand, could significantly affect metabolic pathways. Mainly, interferon (IFN) production following viral infection affects cell function via alteration in amino acid synthesis, membrane composition, and lipid metabolism. Understanding metabolic alterations required for influenza virus replication has revealed novel therapeutic methods based on targeted inhibition of these cellular metabolic pathways.