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Periodontitis (PD) is a prevalent and chronic inflammatory disease with a complex pathogenesis, and it is associated with the presence of specific pathogens, such as Porphyromonas gingivalis. Dysbiosis and dysregulated immune responses ultimately lead to chronic inflammation as well as tooth and alveolar bone loss. Multiple studies have demonstrated that genetic polymorphisms may increase the susceptibility to PD. Furthermore, gene expression is modulated by various epigenetic mechanisms, such as DNA methylation, histone modifications, or the activity of non-coding RNA. These processes can also be induced by PD-associated pathogens. In this review, we try to summarize the genetic processes that are implicated in the pathogenesis of PD. Furthermore, we discuss the use of these mechanisms in diagnosis and therapeutic purposes. Importantly, novel treatment methods that could promote tissue regeneration are greatly needed in PD. In this paper, we also demonstrate current evidence on the potential use of stem cells and extracellular vesicles to stimulate tissue regeneration and suppress inflammation. The understanding of the molecular mechanisms involved in the pathogenesis of PD, as well as the impact of PD-associated bacteria and stem cells in these processes, may enhance future research and ultimately improve long-term treatment outcomes.
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Pérdida de Hueso Alveolar , Periodontitis , Humanos , Periodontitis/genética , Inflamación/genética , Células Madre , Metilación de ADNRESUMEN
INTRODUCTION: This review aims to summarize recent data on the pharmacodynamic, pharmacokinetic, and safety of glucarpidase. This is an enzymatic agent that catalyzes the conversion of methotrexate (MTX) into inactive metabolites. Glucarpidase is used to manage high-dose MTX (HDMTX) toxic plasma concentration, especially in patients with impaired renal function. AREAS COVERED: In this review, studies on glucarpidase clinical efficacy as a therapeutic option for patients suffering from MTX kidney toxicity were presented. Pharmacodynamic and pharmacokinetic properties of glucarpidase were included. Moreover, potential interactions and safety issues were discussed. EXPERT OPINION: The use of glucarpidase is an effective therapeutic strategy in both adults and children treated with high doses of MTX for various types of cancer who have developed acute renal failure. Glucarpidase causes MTX to be converted to nontoxic metabolites and accelerates the time for its complete elimination. After administration of glucarpidase, it is possible to resume HDMTX.
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Lesión Renal Aguda , Metotrexato , Adulto , Niño , Humanos , Antimetabolitos Antineoplásicos/efectos adversos , gamma-Glutamil Hidrolasa/farmacología , gamma-Glutamil Hidrolasa/uso terapéutico , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/tratamiento farmacológicoRESUMEN
INTRODUCTION: Heart failure is a complex clinical syndrome resulting from the unsuccessful compensation of symptoms of myocardial damage. Mitochondrial dysfunction is a process that occurs because of an attempt to adapt to the disruption of metabolic and energetic pathways occurring in the myocardium. This, in turn, leads to further dysfunction in cardiomyocyte processes. Currently, many therapeutic strategies have been implemented to improve mitochondrial function, but their effectiveness varies widely. AREAS COVERED: This review focuses on new models of therapeutic strategies targeting mitochondrial function in the treatment of heart failure. EXPERT OPINION: Therapeutic strategies targeting mitochondria appear to be a valuable option for treating heart failure. Currently, the greatest challenge is to develop new research models that could restore the disrupted metabolic processes in mitochondria as comprehensively as possible. Only the development of therapies that focus on improving as many dysregulated mitochondrial processes as possible in patients with heart failure will be able to bring the expected clinical improvement, along with inhibition of disease progression. Combined strategies involving the reduction of the effects of oxidative stress and mitochondrial dysfunction, appear to be a promising possibility for developing new therapies for a complex and multifactorial disease such as heart failure.
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Insuficiencia Cardíaca , Mitocondrias Cardíacas , Humanos , Mitocondrias Cardíacas/metabolismo , Insuficiencia Cardíaca/tratamiento farmacológico , Miocardio , Miocitos Cardíacos/metabolismo , Estrés OxidativoRESUMEN
INTRODUCTION/OBJECTIVES: Rheumatoid arthritis (RA) is a disease affecting around 1% of the population in developed countries and can be treated with leflunomide. The higher prevalence of RA among women and numerous previous studies suggested the crucial role of sex hormones. Cytochrome CYB5A regulates the synthesis of androgens. Therefore, the aim of this study was to determine the association between common CYB5A gene polymorphism and the response to leflunomide in women with RA. METHODS: This study included 111 patients. All of them received oral leflunomide monotherapy at a dose of 20 mg daily. Women were genotyped for the presence of CYB5A rs1790834 polymorphism and evaluated monthly for 6 months following the initiation of treatment. RESULTS: After 6 months of therapy, patients with the GG genotype had higher DAS28 values and less improvement in DAS28 compared to patients with the GA and AA genotypes (p = 0.04). No statistically significant differences were found in relation to other disease activity parameters. CONCLUSIONS: The results of the current study suggest a possible association of the CYB5A rs1790834 polymorphism with some disease activity parameters in RA patients treated with leflunomide during the initial therapy period. However, confirmation of the effect of this polymorphism on the efficacy of leflunomide treatment requires further studies. Key Points ⢠Leflunomide is the synthetic disease-modifying anti-rheumatic drug used in the therapy of rheumatoid arthritis. ⢠CYB5A rs1790834 gene polymorphism may influence the clinical improvement after 6 months of leflunomide treatment in women with rheumatoid arthritis.
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Antirreumáticos , Artritis Reumatoide , Humanos , Femenino , Leflunamida/uso terapéutico , Isoxazoles/uso terapéutico , Isoxazoles/efectos adversos , Resultado del Tratamiento , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/genética , Artritis Reumatoide/inducido químicamente , Antirreumáticos/efectos adversos , Polimorfismo Genético , Citocromos b5/genéticaRESUMEN
Thymoquinone has been proved to be effective against neoplasms, including skin cancer. Its high lipophilicity, however, may limit its potential use as a drug. Melanoma remains the deadliest of all skin cancers worldwide, due to its high heterogeneity, depending on the stage of the disease. Our goal was to compare the anti-cancer activity of free thymoquinone and thymoquinone-loaded liposomes on two melanoma cell lines that originated from different stages of this cancer: skin-derived A375 and metastatic WM9. We evaluated the proapoptotic effects of free thymoquinone by flow cytometry and Western blot, and its mitotoxicity by means of JC-1 assay. Additionally, we compared the cytotoxicity of free thymoquinone and thymoquinone in liposomes by WST-1 assay. Our results revealed a higher antiproliferative effect of TQ in WM9 cells, whereas its higher proapoptotic activity was observed in the A375 cell line. Moreover, the thymoquinone-loaded liposome was proved to exert stronger cytotoxic effect on both cell lines studied than free thymoquinone. Differences in the response of melanoma cells derived from different stages of the disease to thymoquinone, as well as their different responses to free and carrier-delivered thymoquinone, are essential for the development of new anti-melanoma therapies. However, further research is required to fully understand them.
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Understanding of the gut microbiome's role in human physiology developed rapidly in recent years. Moreover, any alteration of this microenvironment could lead to a pathophysiological reaction of numerous organs. It results from the bidirectional communication of the gastrointestinal tract with the central nervous system, called the gut-brain axis. The signals in the gut-brain axis are mediated by immunological, hormonal, and neural pathways. However, it is also influenced by microorganisms in the gut. The disturbances in the gut-brain axis are associated with gastrointestinal syndromes, but recently their role in the development of different types of pain was reported. The gut microbiome could be the factor in the central sensitization of chronic pain by regulating microglia, astrocytes, and immune cells. Dysbiosis could lead to incorrect immune responses, resulting in the development of inflammatory pain such as endometriosis. Furthermore, chronic visceral pain, associated with functional gastrointestinal disorders, could result from a disruption in the gut microenvironment. Any alteration in the gut-brain axis could also trigger migraine attacks by affecting cytokine expression. Understanding the gut microbiome's role in pain pathophysiology leads to the development of analgetic therapies targeting microorganisms. Probiotics, FODMAP diet, and fecal microbiota transplantation are reported to be beneficial in treating visceral pain.
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Dolor Crónico , Microbioma Gastrointestinal , Microbiota , Probióticos , Dolor Visceral , Femenino , Humanos , Dolor Visceral/patología , Encéfalo/patología , Disbiosis/patología , Microbioma Gastrointestinal/fisiologíaRESUMEN
INTRODUCTION: Rheumatoid arthritis (RA) is a chronic autoimmune disease that reduces the quality of life. The current speed of development of therapeutic agents against RA is not satisfactory. Models on which initial experiments are conducted do not fully reflect human pathogenesis. Overcoming this oversimplification might be a crucial step to accelerate studies on RA treatment. AREAS COVERED: The current approaches to produce novel models or to improve currently available models for the development of RA drugs have been discussed. Advantages and drawbacks of two- and three-dimensional cell cultures and animal models have been described based on recently published results of the studies. Moreover, approaches such as tissue engineering or organ-on-a-chip have been reviewed. EXPERT OPINION: The cell cultures and animal models used to date appear to be of limited value due to the complexity of the processes involved in RA. Current models in RA research should take into account the heterogeneity of patients in terms of disease subtypes, course, and activity. Several advanced models and tools using human cells and tissues have been developed, including three-dimensional tissues, liquid bioreactors, and more complex joint-on-a-chip devices. This may increase knowledge of the molecular mechanisms leading to disease development, to help identify new biomarkers for early detection, and to develop preventive strategies and more effective treatments.
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Artritis Reumatoide , Calidad de Vida , Animales , Humanos , Artritis Reumatoide/tratamiento farmacológico , Biomarcadores , Resultado del TratamientoRESUMEN
Since the end of 2019, the whole world has been struggling with the life-threatening pandemic amongst all age groups and geographic areas caused by Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2). The Coronavirus Disease 2019 (COVID-19) pandemic, which has led to more than 468 million cases and over 6 million deaths reported worldwide (as of 20 March 2022), is one of the greatest threats to human health in history. Meanwhile, the lack of specific and irresistible treatment modalities provoked concentrated efforts in scientists around the world. Various mechanisms of cell entry and cellular dysfunction were initially proclaimed. Especially, mitochondria and cell membrane are crucial for the course of infection. The SARS-CoV-2 invasion depends on angiotensin converting enzyme 2 (ACE2), transmembrane serine protease 2 (TMPRSS2), and cluster of differentiation 147 (CD147), expressed on host cells. Moreover, in this narrative review, we aim to discuss other cell organelles targeted by SARS-CoV-2. Lastly, we briefly summarize the studies on various drugs.
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COVID-19 , Membrana Celular/metabolismo , Humanos , Orgánulos/metabolismo , Peptidil-Dipeptidasa A/metabolismo , SARS-CoV-2RESUMEN
Hydrographic surveys enable the acquisition and processing of bathymetric data, which after being plotted onto nautical charts, can help to ensure safety of navigation, monitor changes in the coastal zone, and assess hydro-engineering structure conditions. This study involves the measurement of waterbody depth, identification of the seabed shape and geomorphology, the coastline course, and the location of underwater obstacles. Hydroacoustic systems mounted on vessels are commonly used in bathymetric measurements. However, there is also an increasing use of Unmanned Aerial Vehicles (UAV) that can employ sensors such as LiDAR (Light Detection And Ranging) or cameras previously not applied in hydrography. Current systems based on photogrammetric and remote sensing methods enable the determination of shallow waterbody depth with no human intervention and, thus, significantly reduce the duration of measurements, especially when surveying large waterbodies. The aim of this publication is to present and compare methods for determining shallow waterbody depths based on an analysis of images taken by UAVs. The perspective demonstrates that photogrammetric techniques based on the SfM (Structure-from-Motion) and MVS (Multi-View Stereo) method allow high accuracies of depth measurements to be obtained. Errors due to the phenomenon of water-wave refraction remain the main limitation of these techniques. It was also proven that image processing based on the SfM-MVS method can be effectively combined with other measurement methods that enable the experimental determination of the parameters of signal propagation in water. The publication also points out that the Lyzenga, Satellite-Derived Bathymetry (SDB), and Stumpf methods allow satisfactory depth measurement results to be obtained. However, they require further testing, as do methods using the optical wave propagation properties.
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Procesamiento de Imagen Asistido por Computador , Dispositivos Aéreos No Tripulados , Fotogrametría , AguaRESUMEN
Siliceous fly ash (FA) is the main additive to currently produced concretes. The utilization of this industrial waste carries an evident pro-ecological factor. In addition, such actions have a positive effect on the structure and mechanical parameters of mature concrete. Unfortunately, the problem of using FA as a Portland cement replacement is that it significantly reduces the performance of concretes in the early stages of their curing. This limits the possibility of using this type of concrete, e.g., in prefabrication, where it is required to obtain high-strength composites after short periods of curing. In order to minimize these negative effects, this research was undertaken to increase the early strength of concretes with FA through the application of a specifically formulated chemical nano-admixture (NA) in the form of seeds of the C-S-H phase. The NA was used to accelerate the strength growth in concretes. Therefore, this paper presents results of tests of modified concretes both with the addition of FA and with innovative NA. The analyses were carried out based on the results of the macroscopic and microstructural tests in five time periods, i.e., after 4, 8, 12, 24 and 72 h. The results of tests carried out with the use of NA clearly indicate the possibility of using FA in a wide range of management areas in sustainable concrete prefabrication.
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Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely available drugs with anti-inflammatory and analgesic properties. Their mechanism of action is associated with the enzymes of the arachidonic acid cycle (cyclooxygenases: COX-1 and COX-2). The cyclooxygenase pathway results in the formation of prostanoids (prostaglandins [PGs], prostacyclins, and thromboxanes). It affects various structures of the human body, including the kidneys. Medical literature associates the usage of NSAIDs with acute kidney injury (AKI), tubulointerstitial nephritis (TIN), as well as nephrotic syndrome and chronic kidney disease (CKD). AKI associated with the chronic consumption of NSAIDs is mainly attributed to pharmacological polytherapy and the presence of cardiovascular or hepatic comorbidities. The pathomechanism of AKI and CKD is associated with inhibition of the biosynthesis of prostanoids involved in the maintenance of renal blood flow, especially PGE2 and PGI2. It is suggested that both COX isoforms play opposing roles in renal function, with natriuresis increased by COX-1 inhibition followed by a drop in a blood pressure, whereas COX-2 inhibition increases blood pressure and promotes sodium retention. TIN after NSAID use is potentially associated with glomerular basement membrane damage, reduction in pore size, and podocyte density. Therefore, nephrotic proteinuria and impairment of renal function may occur. The following article analyzes the association of NSAIDs with kidney disease based on available medical literature.
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Lesión Renal Aguda/inducido químicamente , Antiinflamatorios no Esteroideos/efectos adversos , Nefritis Intersticial/inducido químicamente , Insuficiencia Renal Crónica/inducido químicamente , Animales , HumanosRESUMEN
The use of fly ash in cement composites adversely affects its mechanical properties during the first days of mixture curing. Modern technology, in the form of an admixture containing the hydrated calcium silicates, allows to accelerate the hardening and binding process of concrete. In this paper, studies on the influence of the admixture on properties of concretes with the ordinary Portland cements (OPC) containing the addition of siliceous fly ash (FA) have been carried out. As part of the experimental research, the authors conducted a series of studies for cement pastes modified with the addition of FA and the CSH nano-admixture (NA). In order to compare the mixtures, the following tests of cement pastes were carried out: the compressive and flexural strength, heat of hydration, SEM and rheological shrinkage. The mechanical parameters were tested after 4, 8, 12 and 24 h. The hydration heat test and microstructure analysis were carried out during the first 24 h of the concrete curing. All tests were carried out on the standard samples. On the basis of the heat of hydration test, much higher hydration heat was found in mixtures modified with the NA. During the shrinkage test, a positive effect of the NA was observed-the shrinkage during the first 28 days of mixture curing was lower than in the reference samples. The application of the CSH nano-admixture to cement pastes with the addition of FA has brought positive effects. Apart from a significant increase in strength in the first 24 h of mixture curing, a reduction in the rheological shrinkage was observed. The admixture can be successfully used in the ash concretes, in which a higher early strength is required.
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HLA matching, transplantation technique, or underlying disease greatly influences the probability of long-term transplantation success. It has been hypothesised that genetic variation affecting antigen presentation also contributes to the outcomes of both solid organ transplantation and allogeneic haematopoietic stem cell transplantation (AHSCT). Those genes, along with those responsible for innate and adaptive immunity, have become targets of investigation. In this review, we focus on the role of CTLA4 in the process of acute graft rejection and summarise the progress in our understanding of its role in predicting the outcome. We present the results of the latest studies investigating the link between CTLA4 gene variability and AHSCT, as well as organ transplantation outcomes. While some studies found a link between +49 A/G and -318 C/T and transplantation outcomes, comprehensive meta-analyses have failed to present any association. The most recent field reviews suggest that the -1772 T/C (rs733618) CC genotype is weakly associated with a lower risk of acute graft rejection, while +49 A/G might be clinically meaningful when investigated in the context of combinations with other polymorphisms. Studies verifying associations between 12 CTLA4 gene SNPs and AHSCT outcomes present inexplicit results. Some of the most commonly studied polymorphisms in this context include +49 A/G (rs231775) and CT60 A/G (rs3087243). The results signify that, in order to understand the role of CTLA4 and its gene polymorphisms in transplantology, further studies must be conducted.
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Antígeno CTLA-4/genética , Predisposición Genética a la Enfermedad , Trasplante de Células Madre Hematopoyéticas , Polimorfismo Genético , Humanos , Inmunomodulación , Resultado del TratamientoRESUMEN
The COVID-19 pandemic is one of the greatest threats to human health in the 21st century with more than 257 million cases and over 5.17 million deaths reported worldwide (as of November 23, 2021. Various agents were initially proclaimed to be effective against SARS-CoV-2, the etiological agent of COVID-19. Hydroxychloroquine, lopinavir/ritonavir, and ribavirin are all examples of therapeutic agents, whose efficacy against COVID-19 was later disproved. Meanwhile, concentrated efforts of researchers and clinicians worldwide have led to the identification of novel therapeutic options to control the disease including PAXLOVID™ (PF-07321332). Although COVID-19 cases are currently treated using a comprehensive approach of anticoagulants, oxygen, and antibiotics, the novel Pfizer agent PAXLOVID™ (PF-07321332), an investigational COVID-19 oral antiviral candidate, significantly reduced hospitalization time and death rates, based on an interim analysis of the phase 2/3 EPIC-HR (Evaluation of Protease Inhibition for COVID-19 in High-Risk Patients) randomized, double-blind study of non-hospitalized adult patients with COVID-19, who are at high risk of progressing to severe illness. The scheduled interim analysis demonstrated an 89 % reduction in risk of COVID-19-related hospitalization or death from any cause compared to placebo in patients treated within three days of symptom onset (primary endpoint). However, there still exists a great need for the development of additional treatments, as the recommended therapeutic options are insufficient in many cases. Thus far, mRNA and vector vaccines appear to be the most effective modalities to control the pandemic. In the current review, we provide an update on the progress that has been made since April 2020 in clinical trials concerning the effectiveness of therapies available to combat COVID-19. We focus on currently recommended therapeutic agents, including steroids, various monoclonal antibodies, remdesivir, baricitinib, anticoagulants and PAXLOVID™ summarizing the latest original studies and meta-analyses. Moreover, we aim to discuss other currently and previously studied agents targeting COVID-19 that either show no or only limited therapeutic activity. The results of recent studies report that hydroxychloroquine and convalescent plasma demonstrate no efficacy against SARS-CoV-2 infection. Lastly, we summarize the studies on various drugs with incoherent or insufficient data concerning their effectiveness, such as amantadine, ivermectin, or niclosamide.
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COVID-19 , Preparaciones Farmacéuticas , Adulto , Antivirales/uso terapéutico , COVID-19/terapia , Humanos , Inmunización Pasiva , Lactamas , Leucina , Nitrilos , Pandemias , Prolina , Ensayos Clínicos Controlados Aleatorios como Asunto , SARS-CoV-2 , Resultado del Tratamiento , Sueroterapia para COVID-19RESUMEN
Since the end of 2019, the whole world has been struggling with the pandemic of the new Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2). Available evidence suggests that pain is a common symptom during Coronavirus Disease 2019 (COVID-19). According to the World Health Organization, many patients suffer from muscle pain (myalgia) and/or joint pain (arthralgia), sore throat and headache. The exact mechanisms of headache and myalgia during viral infection are still unknown. Moreover, many patients with respiratory failure get admitted to the intensive care unit (ICU) for ventilatory support. Pain in ICU patients can be associated with viral disease itself (myalgia, arthralgia, peripheral neuropathies), may be caused by continuous pain and discomfort associated with ICU treatment, intermittent procedural pain and chronic pain present before admission to the ICU. Undertreatment of pain, especially when sedation and neuromuscular blocking agents are used, prone positioning during mechanical ventilation or extracorporeal membrane oxygenation (ECMO) may trigger delirium and cause peripheral neuropathies. This narrative review summarizes current knowledge regarding challenges associated with pain assessment and management in COVID-19 patients. A structured prospective evaluation should be undertaken to analyze the probability, severity, sources and adequate treatment of pain in patients with COVID-19 infection.
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In December 2019, a novel coronavirus, SARS-CoV-2, appeared, causing a wide range of symptoms, mainly respiratory infection. In March 2020, the World Health Organization (WHO) declared Coronavirus Disease 2019 (COVID-19) a pandemic, therefore the efforts of scientists around the world are focused on finding the right treatment and vaccine for the novel disease. COVID-19 has spread rapidly over several months, affecting patients across all age groups and geographic areas. The disease has a diverse course; patients may range from asymptomatic to those with respiratory failure, complicated by acute respiratory distress syndrome (ARDS). One possible complication of pulmonary involvement in COVID-19 is pulmonary fibrosis, which leads to chronic breathing difficulties, long-term disability and affects patients' quality of life. There are no specific mechanisms that lead to this phenomenon in COVID-19, but some information arises from previous severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS) epidemics. The aim of this narrative review is to present the possible causes and pathophysiology of pulmonary fibrosis associated with COVID-19 based on the mechanisms of the immune response, to suggest possible ways of prevention and treatment.
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INTRODUCTION: Methotrexate (MTX) is a folate antagonist and a first-line drug for the treatment of rheumatoid arthritis (RA). However, in up to 30% of cases, MTX monotherapy is insufficient, while a further 30% of patients suffer with severe adverse effects. Despite extensive clinical evidence, it is not currently possible to predict therapy outcomes and drug toxicity for MTX. Therefore, to establish biomarkers of toxicity and successful disease remission, pharmacogenomic approaches are rapidly becoming more popular. AREAS: This review summarizes recent pharmacogenomic studies evaluating MTX efficacy and toxicity. In recent years, multiple genetic alterations associated with MTX therapy outcomes and toxicity have been identified in genes associated with MTX metabolism and effector pathways. However, the data are inconsistent and require further validation. EXPERT OPINION: To date, several single nucleotide polymorphisms (SNPs) have been linked with MTX efficacy. However, thanks to equivocal data, pharmacogenomic testing in routine clinical practice remains a distant prospect. Genome-wide association studies (GWAS) could facilitate the evaluation of current SNPs, and support searches for new genetic variations Once achieved, only then will it be possible to introduce more personalized and individualized therapies for RA patients.
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Antirreumáticos/administración & dosificación , Artritis Reumatoide/tratamiento farmacológico , Metotrexato/administración & dosificación , Animales , Antirreumáticos/efectos adversos , Artritis Reumatoide/genética , Biomarcadores/metabolismo , Estudio de Asociación del Genoma Completo , Humanos , Metotrexato/efectos adversos , Farmacogenética , Polimorfismo de Nucleótido Simple , Medicina de Precisión , Resultado del TratamientoRESUMEN
Diabetes mellitus (DM) is a heterogeneous group of disorders whose common trait is chronic hyperglycemia. Gestational diabetes mellitus (GDM) is one of the subtypes of DM that manifests during pregnancy. It is believed that 2%-5% of pregnancies worldwide are complicated with GDM, with the prevalence having significantly increased over the last decade. While the pathogenesis of the disease remains largely unknown, GDM is believed to be a result of interactions between genetic, epigenetic, and environmental factors. Linkage and association studies, including those that are genome-wide, have allowed us to identify complex genetic and epigenetic mechanisms that lead to the development of GDM. Multiple common variants in candidate genes such as potassium inwardly rectifying channel subfamily J, member 11 (KCNJ11), glucokinase (GCK), or hepatocyte nuclear factor 1α (HNF1A) have been found to increase the disease risk. In this review, we provide a detailed overview of the current knowledge concerning the influence of genetics and epigenetics on the development of GDM.
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Diabetes Gestacional/patología , Epigénesis Genética , Ligamiento Genético , Predisposición Genética a la Enfermedad , Diabetes Gestacional/genética , Femenino , Humanos , EmbarazoRESUMEN
Introduction: Rheumatoid arthritis (RA) is an autoimmune disease that is characterized by chronic inflammation of the joints and affects 1% of the population. Polymorphisms of genes that encode proteins that primarily participate in inflammation may influence RA occurrence or become useful biomarkers for certain types of anti-rheumatic treatment.Areas covered: The authors summarize the recent progress in our understanding of the genetics of RA. In the last few years, multiple variants of genes that are associated with RA risk have been identified. The development of new technologies and the detection of new potential therapeutic targets that contribute to novel drug discovery are also described.Expert opinion: There is still the need to search for new genes which may be a potential target for RA therapy. The challenge is to develop appropriate strategies for achieving insight into the molecular pathways involved in RA pathogenesis. Understanding the genetics, immunogenetics, epigenetics and immunology of RA could help to identify new targets for RA therapy. The development of new technologies has enabled the detection of a number of new genes, particularly genes associated with proinflammatory cytokines and chemokines, B- and T-cell activation pathways, signal transducers and transcriptional activators, which might be potential therapeutic targets in RA.
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Antirreumáticos/farmacología , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/genética , Descubrimiento de Drogas , Predisposición Genética a la Enfermedad , Antirreumáticos/uso terapéutico , Humanos , Polimorfismo de Nucleótido SimpleRESUMEN
Background: Umbilical cord blood transplantation is an effective method of curing multiple diseases when there is no donor available for allogeneic hematopoietic stem cell transplantation (AHSCT). It has been recently suggested that polymorphisms in genes affecting antigen presentation could potentially affect cord blood transplantation (CBT) outcomes.Areas covered: In this review, we present the results of the latest studies investigating the link between CTLA4 gene variability and umbilical cord blood transplantation outcomes.Expert opinion: The search for genetic variants that influence the immune response, both innate and adaptive immunity, may lead to more optimal therapies. Promising candidate genes are those that regulate the expression of proteins associated with T-cell activation. Many genetic variants could be therapeutically important, including those related to innate and adaptive immunity, cytokines, chemokines, drug-metabolizing enzymes, drug transporters, and inflammatory enzymes. The development of an algorithm that includes the determination of selected genetic variants could be helpful for an appropriate donor-recipient CBT matching.