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1.
Sci Total Environ ; 773: 145442, 2021 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-33940727

RESUMEN

Cadmium (Cd) has been confirmed as an environmental contaminant, which potential threats health impacts to humans and animals. Selenium (Se) as a beneficial element that alleviates the negative effects of Cd toxicity. Se mainly exists in two forms in food nutrients including organic Se usually as (Se-enriched yeast (SeY)) and inorganic Se (sodium selenite (SSe)). Nanoparticle of Se (Nano-Se), a new form Se, which is synthesized by the bioreduction of Se species, which attracted significant attention recently. However, compared the superiority alleviation effects of Nano-Se, SeY or SSe on Cd-induced toxicity and related mechanisms are still poorly understood. The purpose of this study was to compare the superiority antagonism effects of Nano-Se, SeY and SSe on Cd-induced inflammation response via NF-kB/IκB pathway in the heart. The present study demonstrated that exposed to Cd obviously increased the accumulation of Cd, disruption of ion homeostasis and depressed the ratios of K+/Na+ and Mg2+/Ca2+ via ion chromatography mass spectrometry (ICP-MS) detecting the heart specimens. In the results of histological and ultrastructure observation, typical inflammatory infiltrate characteristics and mitochondria and nuclear structure alterations in the hearts of Cd group were confirmed. Cd treatment enhanced the inducible nitric oxide synthase (iNOS) activities and NOS isoforms expression via NF-kB/IκB pathway to promote inflammation response. However, the combined treatment of Cd-exposed animals with Nano-Se was more effective than SeY and SSe in reversing Cd-induced histopathological changes and iNOS activities increased, reducing Cd accumulation and antagonizing Cd-triggered inflammation response via NF-kB/IκB pathway in chicken hearts. Overall, Se applications, especially Nano-Se, can be most efficiently used for relieving cardiotoxicity by exposed to Cd compared to other Se compound.


Asunto(s)
Nanopartículas , Selenio , Animales , Cadmio/toxicidad , Humanos , Inflamación/inducido químicamente , FN-kappa B , Nanopartículas/toxicidad , Saccharomyces cerevisiae , Selenito de Sodio
2.
BMC Complement Med Ther ; 21(1): 112, 2021 Apr 07.
Artículo en Inglés | MEDLINE | ID: mdl-33827515

RESUMEN

BACKGROUND: Elderberry has traditionally been used to prevent and treat respiratory problems. During the COVID-19 pandemic, there has been interest in elderberry supplements to treat or prevent illness, but also concern that elderberry might overstimulate the immune system and increase the risk of 'cytokine storm'. We aimed to determine benefits and harms of elderberry for the prevention and treatment of viral respiratory infections, and to assess the relationship between elderberry supplements and negative health impacts associated with overproduction of pro-inflammatory cytokines. METHODS: We conducted a systematic review and searched six databases, four research registers, and two preprint sites for studies. Two reviewers independently assessed studies for inclusion, extracted data from studies, assessed risk of bias using Cochrane tools, and evaluated certainty of estimates using GRADE. Outcomes included new illnesses and the severity and duration of illness. RESULTS: We screened 1187 records and included five randomized trials on elderberry for the treatment or prevention of viral respiratory illness. We did not find any studies linking elderberry to clinical inflammatory outcomes. However, we found three studies measuring production of cytokines ex vivo after ingestion of elderberry. Elderberry may not reduce the risk of developing the common cold; it may reduce the duration and severity of colds, but the evidence is uncertain. Elderberry may reduce the duration of influenza but the evidence is uncertain. Compared to oseltamivir, an elderberry-containing product may be associated with a lower risk of influenza complications and adverse events. We did not find evidence on elderberry and clinical outcomes related to inflammation. However, we found evidence that elderberry has some effect on inflammatory markers, although this effect may decline with ongoing supplementation. One small study compared elderberry to diclofenac (a nonsteroidal anti-inflammatory drug) and provided some evidence that elderberry is as effective or less effective than diclofenac in cytokine reduction over time. CONCLUSIONS: Elderberry may be a safe option for treating viral respiratory illness, and there is no evidence that it overstimulates the immune system. However, the evidence on both benefits and harms is uncertain and information from recent and ongoing studies is necessary to make firm conclusions.


Asunto(s)
/tratamiento farmacológico , Resfriado Común/tratamiento farmacológico , Citocinas/metabolismo , Gripe Humana/tratamiento farmacológico , Fitoterapia , Extractos Vegetales/uso terapéutico , Sambucus , /metabolismo , Resfriado Común/metabolismo , Humanos , Inflamación/metabolismo , Inflamación/prevención & control , Gripe Humana/metabolismo , Pandemias
3.
Medicine (Baltimore) ; 100(14): e25408, 2021 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-33832136

RESUMEN

BACKGROUND: Acute respiratory distress syndrome (ARDS) is caused by an inflammatory injury to the lung. Dysregulated inflammation is the cardinal feature of ARDS. Methylprednisolone is an option for treating ARDS. However, the benefits and adverse effects of methylprednisolone have not been well assessed in patients with ARDS. This study aimed to evaluate the efficacy and safety of methylprednisolone against ARDS. MATERIAL AND METHODS: The electronic database of Embase, PubMed, the Cochrane Library, CNKI, and Wanfang were searched, and randomized controlled trials (RCTs) reporting the efficacy and safety of methylprednisolone for ARDS were included. Revman 5.3 and Stata 15.0 were used to conduct the analysis. The fixed-effects model was used to calculate summary odds ratios (ORs) and 95% confidence interval (CIs). RESULTS: Ten RCTs studies involving 692 patients with ARDS. The summary results demonstrated that, compared with placebo, methylprednisolone had a statistically significant effect on mortality (OR = 0.64; 95% CI: 0.43-0.95, I2 = 42%); the time of mechanical ventilation (MD) = -2.70, 95% CI: -3.31 to -2.10; I2 = 0%) in patients with ARDS, but it was not associated with increased rates of adverse events (OR = 0.80; 95% CI: 0.34-1.86; I2 = 58%). CONCLUSIONS: This systematic review and meta-analysis demonstrated that Methylprednisolone is safe against ARDS. It may reduce mortality and shorten the time of mechanical ventilation. However, well-designed and large-sample studies were required to fully characterize the efficacy and safety of methylprednisolone against ARDS.


Asunto(s)
Antiinflamatorios/uso terapéutico , Metilprednisolona/uso terapéutico , Respiración Artificial/estadística & datos numéricos , /tratamiento farmacológico , Adulto , Anciano , Antiinflamatorios/efectos adversos , Estudios de Casos y Controles , Manejo de Datos , Humanos , Inflamación/fisiopatología , Metilprednisolona/efectos adversos , Persona de Mediana Edad , Mortalidad/tendencias , Placebos/administración & dosificación , Ensayos Clínicos Controlados Aleatorios como Asunto , /patología , Seguridad , Resultado del Tratamiento
4.
Wiad Lek ; 74(1): 64-67, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33851589

RESUMEN

OBJECTIVE: The aim: To evaluate the parameters of menstrual function in 1015 women of reproductive age and to establish the relationship between the detected menstrual disorders and the development of migraine and/or irritable bowel syndrome (IBS). PATIENTS AND METHODS: Materials and methods: During 2018-2020, a survey of women of reproductive age in the Ternopil region (Ukraine) was conducted. To interview the study respondents, we developed a questionnaire that assessed the parameters of menstrual function (age of menarche; regularity and cyclicity of menstrual changes; duration of the menstrual cycle and menstruation itself; the amount of blood loss with the pictogram, the presence of clots and their size) identify characteristic changes in health, symptoms of irritable bowel syndrome and migraine associated with the menstrual cycle. Data analysis was performed by statistical and mathematical method. RESULTS: Results and conclusions: In 72.2 % of respondents, the study revealed deviations from the normal course of the menstrual cycle. In particular, an increase in blood loss during menstruation and the appearance of clots larger than 1 cm were observed in 40.8 % of women. Among patients with menstrual dysfunction, 51.8 % of patients had symptoms of irritable bowel syndrome, and 44.1 % had signs of migraine. Thus, the relationship between cyclic menstrual disorders and the formation of IBS and migraine, which significantly affects the deterioration of health, performance of women of childbearing age.


Asunto(s)
Síndrome del Colon Irritable , Ciclo Menstrual , Femenino , Humanos , Inflamación , Síndrome del Colon Irritable/complicaciones , Trastornos de la Menstruación , Ucrania
5.
Wiad Lek ; 74(1): 161-164, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33851608

RESUMEN

A very rare inflammatory disease of CNS, CLIPPERS syndrome, was recently described and only a few sporadic cases are reported in the medical literature. Its etiology and pathogenesis are unknown, that together with the polymorphic and sometimes confounding neurological manifestations, and radiological findings represent a real diagnostic and therapeutic challenge for clinicians. Aim: To highlight the importance of clear and specific diagnostic assessment. Here we present the case of a 40-year-old male with a subacute lymphocytic midbrain inflammation accompanied by vasculitis. We discuss the symptoms, imaging and treatment of this lesion.


Asunto(s)
Imagen por Resonancia Magnética , Puente , Adulto , Tronco Encefálico , Humanos , Inflamación , Masculino , Síndrome
6.
RMD Open ; 7(1)2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33790049

RESUMEN

BACKGROUND: The CHIC study (COVID-19 High-intensity Immunosuppression in Cytokine storm syndrome) is a quasi-experimental treatment study exploring immunosuppressive treatment versus supportive treatment only in patients with COVID-19 with life-threatening hyperinflammation. Causal inference provides a means of investigating causality in non-randomised experiments. Here we report 14-day improvement as well as 30-day and 90-day mortality. PATIENTS AND METHODS: The first 86 patients (period 1) received optimal supportive care only; the second 86 patients (period 2) received methylprednisolone and (if necessary) tocilizumab, in addition to optimal supportive care. The main outcomes were 14-day clinical improvement and 30-day and 90-day survival. An 80% decline in C reactive protein (CRP) was recorded on or before day 13 (CRP >100 mg/L was an inclusion criterion). Non-linear mediation analysis was performed to decompose CRP-mediated effects of immunosuppression (defined as natural indirect effects) and non-CRP-mediated effects attributable to natural prognostic differences between periods (defined as natural direct effects). RESULTS: The natural direct (non-CRP-mediated) effects for period 2 versus period 1 showed an OR of 1.38 (38% better) for 14-day improvement and an OR of 1.16 (16% better) for 30-day and 90-day survival. The natural indirect (CRP-mediated) effects for period 2 showed an OR of 2.27 (127% better) for 14-day improvement, an OR of 1.60 (60% better) for 30-day survival and an OR of 1.49 (49% better) for 90-day survival. The number needed to treat was 5 for 14-day improvement, 9 for survival on day 30, and 10 for survival on day 90. CONCLUSION: Causal inference with non-linear mediation analysis further substantiates the claim that a brief but intensive treatment with immunosuppressants in patients with COVID-19 and systemic hyperinflammation adds to rapid recovery and saves lives. Causal inference is an alternative to conventional trial analysis, when randomised controlled trials are considered unethical, unfeasible or impracticable.


Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Proteína C-Reactiva/inmunología , Síndrome de Liberación de Citoquinas/tratamiento farmacológico , Glucocorticoides/uso terapéutico , Inmunosupresores/uso terapéutico , Metilprednisolona/uso terapéutico , /inmunología , Causalidad , Síndrome de Liberación de Citoquinas/inmunología , Estudio Históricamente Controlado , Humanos , Inflamación/inmunología , Mortalidad , Tasa de Supervivencia , Resultado del Tratamiento
7.
Artículo en Inglés | MEDLINE | ID: mdl-33801527

RESUMEN

The strong spread of COVID-19 and the significant number of deaths associated with it could be related to improper lifestyles, which lead to a low-grade inflammation (LGI) that not only increases the risk of chronic diseases, but also the risk of facing complications relating to infections and a greater susceptibility to infections themselves. Recently, scientific research has widely demonstrated that the microbiota plays a fundamental role in modulating metabolic responses in the immune system. There is, in fact, a two-way interaction between lifestyle, infection, and immunity. The immune response is compromised if nutrition is unbalanced or insufficient, because diet affects the intestinal flora predisposing people to infections and, at the same time, the nutritional state can be aggravated by the immune response itself to the infection. We evaluate the link between balanced diet, the efficiency of the immune system, and microbiota with the aim of providing some practical advice for individuals, with special attention to the elderly. A correct lifestyle that follows the Mediterranean model, which is especially rich in plant-based foods along with the use of extra-virgin olive oil, are the basis of preventing LGI and other chronic pathologies, directly influencing the intestinal microbiota and consequently the immune response.


Asunto(s)
Dieta Mediterránea , Virosis , Anciano , Dieta , Humanos , Sistema Inmunológico , Inflamación , Aceite de Oliva
8.
Nutrients ; 13(3)2021 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-33804603

RESUMEN

Severe obesity is associated with an increased risk of admission to intensive care units and need for invasive mechanical ventilation in patients with COVID-19. The association of obesity and COVID-19 prognosis may be related to many different factors, such as chronic systemic inflammation, the predisposition to severe respiratory conditions and viral infections. The ketogenic diet is an approach that can be extremely effective in reducing body weight and visceral fat in the short term, preserving the lean mass and reducing systemic inflammation. Therefore, it is a precious preventive measure for severely obese people and may be considered as an adjuvant therapy for patients with respiratory compromise.


Asunto(s)
/dietoterapia , Dieta Cetogénica/métodos , /etiología , Humanos , Inflamación/prevención & control , Obesidad/complicaciones , Sistema Respiratorio/fisiopatología , Sistema Respiratorio/virología
9.
Orv Hetil ; 162(16): 602-607, 2021 04 07.
Artículo en Húngaro | MEDLINE | ID: mdl-33830937

RESUMEN

Összefoglaló. Újabb megfigyelések szerint a SARS-CoV-2-fertozést követoen gyermekekben a paediatric inflammatory multisystem syndrome (PIMS) elnevezésu, sokkállapottal szövodött Kawasaki-megbetegedéshez hasonlító, többszervi elégtelenségnek megfelelo tünetegyüttes alakulhat ki. A gyermekek többségében ilyenkor a direkt víruskimutatás már sikertelen, azonban a SARS-CoV-2 ellen képzodött antitest igazolhatja a diagnózist. Dolgozatunk célja az egyik elso hazai eset ismertetése. Egy 15 éves fiú került gyermek intenzív osztályos felvételre több napon át észlelt magas láz, kesztyu-, zokniszeru exanthema, conjunctivitis, többszervi elégtelenség, szeptikus sokk tüneteivel, akut gyulladásra utaló laboratóriumi eltérésekkel és diffúz hasi panaszokkal. Felvételét megelozoen néhány héttel SARS-CoV-2-fertozésen esett át. Felvételekor a direkt víruskimutatás sikertelen volt, ám a SARS-CoV-2 elleni antitest vizsgálata pozitív lett. Komplex intenzív terápia mellett állapota stabilizálódott. Az irodalmi ajánlásoknak megfeleloen immunglobulin-, acetilszalicilsav- és szteroidkezelésben részesítettük, melynek hatására állapota maradványtünetek nélkül rendezodött. A növekvo esetszámú gyermekkori SARS-CoV-2-fertozés mellett egyre gyakrabban várható a SARS-CoV-2-fertozést követo, a Kawasaki-betegség tüneteire emlékezteto PIMS kialakulása. Gyermekekben súlyos szeptikus állapot és többszervi elégtelenség esetén gondolni kell a PIMS lehetoségére, mely esetenként intenzív osztályos ellátást és célzott terápiát igényel. Legjobb tudomásunk szerint a leírásra került beteg a Magyarországon diagnosztizált egyik legkorábbi eset. Orv Hetil. 2021; 162(16): 602-607. Summary. Recently following SARS-CoV-2 infection, a new, multisystem disease (paediatric inflammatory multisystem syndrome, PIMS) with fever was recognized in children with shock and multiorgan failure. On of the first Hungarian cases will be described. A 15-year-old boy was admitted to the Paediatric Intensive Care Unit with persistent high fever, diffuse abdominal pain, septic shock, multiple organ failure, gloves- and socks-shaped cutan exanthema, conjunctivitis and laboratory signs of inflammation. Some weeks preceding his admission, symptoms of mild SARS-CoV-2 infection were revealed. At admission, the SARS-CoV-2 PCR and antigen tests were negative, however, the presence of IgG antibody was shown. Following complex supportive intensive care along with internationally recommended immunoglobulin, aspirin and steroid treatment, the patient was completely cured without any sequalae. In children after SARS-CoV-2 infection, PIMS could occur mimicking Kawasaki syndrome. At this time, in children virus PCR or antigen tests are usually negative already, but the presence of SARS-CoV-2 antibody could prove the preceding disease. Due to the increasing number of SARS-CoV-2 infections, the occurrence of post-SARS-CoV-2 PIMS in childhood is expected to increase. For paediatric patients, in case of severe septic state and multiple organ failure, PIMS should be also considered, which may require intensive care and targeted therapy. As far as we know, the described case is one of the earliest cases of PIMS in Hungary. Orv Hetil. 2021; 162(16): 602-607.


Asunto(s)
Dolor Abdominal/etiología , Fiebre/etiología , Inmunoglobulina G/sangre , Síndrome de Respuesta Inflamatoria Sistémica , Adolescente , /virología , Conjuntivitis/virología , Exantema/virología , Hospitalización , Humanos , Hungría , Inflamación/virología , Unidades de Cuidado Intensivo Pediátrico , Masculino , Insuficiencia Multiorgánica/virología , Choque Séptico/virología , Síndrome de Respuesta Inflamatoria Sistémica/sangre , Síndrome de Respuesta Inflamatoria Sistémica/virología
10.
Adv Exp Med Biol ; 1310: 495-507, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33834447

RESUMEN

Skin is vulnerable to various external insults such as burn, severe injury, or inflammation, which necessitates a better strategy for wound repair. Mesenchymal stem cells (MSCs) can self-renew and differentiate into various supporting tissues including cartilage, bone, muscle, and adipose tissue. Along with their unique multipotent capacity, they secrete various paracrine mediators such as growth factors, cytokines, and membrane-enclosed particles called extracellular vesicles (EVs). Herein, we discussed the general traits of EVs such as cell-to-cell communicator, and highlighted the recent preclinical outcomes, with a focus on the application of MSC-derived EVs in wound repair. This chapter provides insights into developing novel strategies for skin wound healing in a cell-free manner.


Asunto(s)
Vesículas Extracelulares , Células Madre Mesenquimatosas , Citocinas , Humanos , Inflamación , Cicatrización de Heridas
11.
Klin Lab Diagn ; 66(3): 177-180, 2021 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-33793118

RESUMEN

Immunomodulatory drugs are widely used as drugs for the treatment of inflammatory diseases of microbial etiology in clinical medicine. The authors evaluated the effectiveness of the therapeutic effect of the Cycloferon immunomodulator in the treatment of chronic purulent-inflammatory diseases of the reproductive tract using clinical, microbiological and immunological parameters. It was shown that under the influence of immunomodulatory therapy, the restoration of the qualitative and quantitative composition of the normoflora was observed with the elimination of etiologically significant microorganisms. The immunocorrective effect of therapy on the indices of local immunity was established: the concentration of lactoferrin increased in the cervical secretion, the level of cytokines IL-1ß and γ-IFN normalized, the amount of secretory IgA increased significantly, which contributed to the enhancement of local protective reactions, as well as the clinical efficacy of therapy, which was manifested in the reduction and/or disappearance of pain syndrome and the absence of relapse for 2 or more years. Conducted researches allow us to speak of immunotropic drugs as a promising direction in the treatment of inflammatory processes of the reproductive tract, a significant advantage of which is rational immunomodulation directly in the focus of inflammation, the availability of treatment, the absence of side effects with adequate therapeutic regimens, which makes it relevant to further study this direction of immunocorrection and its implementation into wide clinical practice.


Asunto(s)
Citocinas , Inmunomodulación , Humanos , Inmunidad , Inflamación
12.
Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi ; 35(4): 306-311;315, 2021 Apr.
Artículo en Chino | MEDLINE | ID: mdl-33794626

RESUMEN

Objective:This study aimed to explore the biomarkers in nasal secretion that can assist in the diagnosis of allergic rhinitis(AR) and can be used to evaluate the therapeutic effect of AR. Methods:Thirty-three patients with AR and 21 healthy controls were included. The nasal secretion of healthy controls and patients with AR(before and after treatment) were collected. The cytology, the concentrations of cytokines(IL-5, IL-6, IL-8, IL-33, IFN-γ) and inflammatory mediators(ECP, MPO) were detected. Then, we compared the differences of various biomarkers between healthy controls and AR patients(before and after treatment group). And analyzed the correlation between each biomarkers/biomarkers difference value/the percentage of biomarkers difference value and clinical symptom score/ score difference value / the percentage of score difference value. Results:Compared with normal controls, the levels of ECP, IL-5, IL-6, IL-8, IL-33 and IFN-γ in nasal secretion of AR patients were significantly higher than those of normal controls(P<0.05). There was no significant difference in MPO. After treatment, ECP decreased significantly(P<0.01), inflammatory cell grade and eosinophil percentage are also decreased(P<0.01). However, MPO, IL-5, IL-6, IL-8, IL-33 and IFN-γ did not change significantly. The difference value of ECP before and after treatment was correlated with the difference value of VAS score(r=0.348, P=0.047). The difference value of IL-5 was correlated with the difference value of VAS score and rhinorrhea, the correlation coefficients were 0.406(P=0.019) and 0.429(P=0.013), respectively. The difference value of eosinophil percentage in nasal secretion before and after treatment was correlated with nasal congestion, and the correlation coefficient was 0.383. The difference value of eosinophil percentage multiplied by inflammatory cell grade before and after treatment was correlated with VAS score(r=0.417, P=0.016) and nasal congestion difference value(r=0.519, P=0.002). The percentage of difference value of IFN-γ before and after treatment was correlated with the percentage of difference value of VAS score / rhinorrhea / sneeze / total nasal symptom score. Conclusion:ECP, IL-6, IL-8 and IL-33 in nasal secretion are expected to be objective biomarkers for auxiliary diagnosis of AR. And ECP, IL-5, IFN-γ, eosinophil percentage multiplied by grade is expected to be an objective index to judge the improvement of patients' symptoms after treatment.


Asunto(s)
Rinitis Alérgica , Biomarcadores , Eosinófilos , Humanos , Inflamación , Mucosa Nasal , Nariz , Rinitis Alérgica/diagnóstico
13.
Int J Mol Sci ; 22(6)2021 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-33804769

RESUMEN

SARS-CoV-2 infection can cause cytokine storm and may overshoot immunity in humans; however, it remains to be determined whether virus-induced soluble mediators from infected cells are carried by exosomes as vehicles to distant organs and cause tissue damage in COVID-19 patients. We took an unbiased proteomic approach for analyses of exosomes isolated from plasma of healthy volunteers and COVID-19 patients. Our results revealed that tenascin-C (TNC) and fibrinogen-ß (FGB) are highly abundant in exosomes from COVID-19 patients' plasma compared with that of healthy normal controls. Since TNC and FGB stimulate pro-inflammatory cytokines via the Nuclear factor-κB (NF-κB) pathway, we examined the status of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and C-C motif chemokine ligand 5 (CCL5) expression upon exposure of hepatocytes to exosomes from COVID-19 patients and observed significant increase compared with that from healthy subjects. Together, our results demonstrate that TNC and FGB are transported through plasma exosomes and potentially trigger pro-inflammatory cytokine signaling in cells of distant organ.


Asunto(s)
/sangre , Exosomas/química , Exosomas/genética , Fibrinógeno/metabolismo , Inflamación/metabolismo , Tenascina/metabolismo , Anciano , Línea Celular , Quimiocina CCL5/metabolismo , Exosomas/metabolismo , Exosomas/ultraestructura , Femenino , Hepatocitos/metabolismo , Humanos , Inflamación/etiología , Interleucina-6/metabolismo , Masculino , Espectrometría de Masas , Microscopía Electrónica de Transmisión , Persona de Mediana Edad , FN-kappa B/metabolismo , Mapas de Interacción de Proteínas , Proteoma/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo
14.
Genes (Basel) ; 12(3)2021 03 22.
Artículo en Inglés | MEDLINE | ID: mdl-33809949

RESUMEN

The coronavirus disease 2019 (COVID-19) pandemic has caused more than 2.3 million casualties worldwide and the lack of effective treatments is a major health concern. The development of targeted drugs is held back due to a limited understanding of the molecular mechanisms underlying the perturbation of cell physiology observed after viral infection. Recently, several approaches, aimed at identifying cellular proteins that may contribute to COVID-19 pathology, have been reported. Albeit valuable, this information offers limited mechanistic insight as these efforts have produced long lists of cellular proteins, the majority of which are not annotated to any cellular pathway. We have embarked in a project aimed at bridging this mechanistic gap by developing a new bioinformatic approach to estimate the functional distance between a subset of proteins and a list of pathways. A comprehensive literature search allowed us to annotate, in the SIGNOR 2.0 resource, causal information underlying the main molecular mechanisms through which severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and related coronaviruses affect the host-cell physiology. Next, we developed a new strategy that enabled us to link SARS-CoV-2 interacting proteins to cellular phenotypes via paths of causal relationships. Remarkably, the extensive information about inhibitors of signaling proteins annotated in SIGNOR 2.0 makes it possible to formulate new potential therapeutic strategies. The proposed approach, which is generally applicable, generated a literature-based causal network that can be used as a framework to formulate informed mechanistic hypotheses on COVID-19 etiology and pathology.


Asunto(s)
Autofagia/genética , /virología , Interacciones Microbiota-Huesped/genética , Transducción de Señal , /genética , Ontología de Genes , Redes Reguladoras de Genes , Humanos , Inflamación/genética , Inflamación/metabolismo , Inflamación/virología , Proteoma , PubMed , /patogenicidad , Transducción de Señal/genética
15.
Mediators Inflamm ; 2021: 8812304, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33814982

RESUMEN

Objective: Coronavirus disease 2019 (COVID-19) is a considerable global public health threat. This study sought to investigate whether blood glucose (BG) levels or comorbid diabetes are associated with inflammatory status and disease severity in patients with COVID-19. Methods: In this retrospective cohort study, the clinical and biochemical characteristics of COVID-19 patients with or without diabetes were compared. The relationship among severity of COVID-19, inflammatory status, and diabetes or hyperglycemia was analyzed. The severity of COVID-19 in all patients was determined according to the diagnostic and treatment guidelines issued by the Chinese National Health Committee (7th edition). Results: Four hundred and sixty-one patients were enrolled in our study, and 71.58% of patients with diabetes and 13.03% of patients without diabetes had hyperglycemia. Compared with patients without diabetes (n = 366), patients with diabetes (n = 95) had a higher leucocyte count, neutrophil count, neutrophil to lymphocyte ratio (NLR), and erythrocyte sedimentation rate (ESR). There was no association between severity of COVID-19 and known diabetes adjusted for age, sex, body mass index (BMI), known hypertension, and coronary heart disease. The leucocyte count, NLR, and C-reactive protein (CRP) level increased with increasing BG level. Hyperglycemia was an independent predictor of critical (OR 4.00, 95% CI 1.72-9.30) or severe (OR 3.55, 95% CI 1.47-8.58) COVID-19, and of increased inflammatory levels (high leucocyte count (OR 4.26, 95% CI 1.65-10.97), NLR (OR 2.76, 95% CI 1.24-6.10), and CRP level (OR 2.49, 95% CI 1.19-5.23)), after adjustment for age, sex, BMI, severity of illness, and known diabetes. Conclusion: Hyperglycemia was positively correlated with higher inflammation levels and more severe illness, and it is a risk factor for the increased severity of COVID-19. The initial measurement of plasma glucose levels after hospitalization may help identify a subset of patients who are predisposed to a worse clinical course.


Asunto(s)
/sangre , Hiperglucemia/sangre , Hiperglucemia/complicaciones , Inflamación/sangre , Inflamación/complicaciones , Anciano , Glucemia/metabolismo , Sedimentación Sanguínea , Proteína C-Reactiva/metabolismo , China/epidemiología , Complicaciones de la Diabetes/sangre , Femenino , Humanos , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Pandemias , Estudios Retrospectivos , Factores de Riesgo , Índice de Severidad de la Enfermedad
16.
Zhongguo Dang Dai Er Ke Za Zhi ; 23(4): 420-424, 2021 Apr.
Artículo en Chino | MEDLINE | ID: mdl-33840417

RESUMEN

Compared with adults, children tend to have lower incidence rate, hospitalization rate, and mortality rate of coronavirus disease 2019 (COVID-19), while the cause of such age-based differences in disease severity remains unclear. An investigation of pathogenesis in children may help to analyze the therapies for the high-risk population. Human angiotensin-converting enzyme Ⅱ is the main receptor of severe acute respiratory syndrome coronavirus 2 and can limit pulmonary capillary leakage and inflammation mediated by angiotensin 2 and exert a protective effect against acute lung injury. Its expression decreases with age. Regular vaccination and frequent upper respiratory virus infection in children can lead to regular immune activation, and its combination with strong innate immunity can help to achieve virus clearance in the early stage of infection in children with COVID-19. Meanwhile, there are strong regeneration and repair abilities of alveolar epithelial cells in children, which may help with the early recovery of infection. In addition, risk factors, such as underlying cardiopulmonary diseases, obesity, and smoking, are relatively uncommon in children. Social factors, including home quarantine and timely closure of schools, may help to reduce the infection rate in children. However, children with immunodeficiency are a high-risk population and should be closely monitored. Further studies are needed to investigate the immune and protection mechanisms against COVID-19 in children.


Asunto(s)
Adulto , Niño , Humanos , Inflamación , Pulmón , Factores de Riesgo
17.
Int J Mol Sci ; 22(6)2021 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-33809214

RESUMEN

Extracellular vesicles (EVs) are generated and secreted by cells into the circulatory system. Stem cell-derived EVs have a therapeutic effect similar to that of stem cells and are considered an alternative method for cell therapy. Accordingly, research on the characteristics of EVs is emerging. EVs were isolated from human epidural fat-derived mesenchymal stem cells (MSCs) and human fibroblast culture media by ultracentrifugation. The characterization of EVs involved the typical evaluation of cluster of differentiation (CD antigens) marker expression by fluorescence-activated cell sorting, size analysis with dynamic laser scattering, and morphology analysis with transmission electron microscopy. Lastly, the secreted levels of cytokines and chemokines in EVs were determined by a cytokine assay. The isolated EVs had a typical size of approximately 30-200 nm, and the surface proteins CD9 and CD81 were expressed on human epidural fat MSCs and human fibroblast cells. The secreted levels of cytokines and chemokines were compared between human epidural fat MSC-derived EVs and human fibroblast-derived EVs. Human epidural fat MSC-derived EVs showed anti-inflammatory effects and promoted macrophage polarization. In this study, we demonstrated for the first time that human epidural fat MSC-derived EVs exhibit inflammatory suppressive potency relative to human fibroblast-derived EVs, which may be useful for the treatment of inflammation-related diseases.


Asunto(s)
Diferenciación Celular/genética , Vesículas Extracelulares/genética , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas/citología , Animales , Polaridad Celular/genética , Tratamiento Basado en Trasplante de Células y Tejidos , Quimiocinas/genética , Citocinas/genética , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/trasplante , Fibroblastos/citología , Fibroblastos/metabolismo , Regulación de la Expresión Génica/genética , Humanos , Inflamación/genética , Inflamación/terapia , Macrófagos/metabolismo , Células Madre Mesenquimatosas/metabolismo
18.
Int J Mol Sci ; 22(6)2021 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-33809261

RESUMEN

Lipin2 is a phosphatidate phosphatase that plays critical roles in fat homeostasis. Alterations in Lpin2, which encodes lipin2, cause the autoinflammatory bone disorder Majeed syndrome. Lipin2 limits lipopolysaccharide (LPS)-induced inflammatory responses in macrophages. However, little is known about the precise molecular mechanisms underlying its anti-inflammatory function. In this study, we attempted to elucidate the molecular link between the loss of lipin2 function and autoinflammatory bone disorder. Using a Lpin2 knockout murine macrophage cell line, we showed that lipin2 deficiency enhances innate immune responses to LPS stimulation through excessive activation of the NF-κB signaling pathway, partly because of TAK1 signaling upregulation. Lipin2 depletion also enhanced RANKL-mediated osteoclastogenesis and osteoclastic resorption activity accompanied by NFATc1 dephosphorylation and increased nuclear accumulation. These results suggest that lipin2 suppresses the development of autoinflammatory bone disorder by fine-tuning proinflammatory responses and osteoclastogenesis in macrophages. Therefore, this study provides insights into the molecular pathogenesis of monogenic autoinflammatory bone disorders and presents a potential therapeutic intervention.


Asunto(s)
Anemia Diseritropoyética Congénita/genética , Síndromes de Inmunodeficiencia/genética , Inflamación/genética , Quinasas Quinasa Quinasa PAM/genética , Factores de Transcripción NFATC/genética , Proteínas Nucleares/genética , Osteomielitis/genética , Tejido Adiposo/metabolismo , Tejido Adiposo/patología , Anemia Diseritropoyética Congénita/metabolismo , Anemia Diseritropoyética Congénita/patología , Animales , Resorción Ósea/genética , Resorción Ósea/metabolismo , Resorción Ósea/patología , Diferenciación Celular/genética , Humanos , Síndromes de Inmunodeficiencia/metabolismo , Síndromes de Inmunodeficiencia/patología , Inflamación/metabolismo , Inflamación/patología , Lipopolisacáridos/genética , Macrófagos/metabolismo , Macrófagos/patología , Ratones , Ratones Noqueados , FN-kappa B/genética , Proteínas Nucleares/deficiencia , Proteínas Nucleares/metabolismo , Osteoclastos/metabolismo , Osteogénesis/genética , Osteomielitis/metabolismo , Osteomielitis/patología , Ligando RANK/genética , Transducción de Señal/genética , Factor de Transcripción ReIA/genética
19.
Int J Mol Sci ; 22(7)2021 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-33810314

RESUMEN

TRPA1, a nonselective cation channel, is expressed in sensory afferent that innervates peripheral targets. Neuronal TRPA1 can promote tissue repair, remove harmful stimuli and induce protective responses via the release of neuropeptides after the activation of the channel by chemical, exogenous, or endogenous irritants in the injured tissue. However, chronic inflammation after repeated noxious stimuli may result in the development of several diseases. In addition to sensory neurons, TRPA1, activated by inflammatory agents from some non-neuronal cells in the injured area or disease, might promote or protect disease progression. Therefore, TRPA1 works as a molecular sentinel of tissue damage or as an inflammation gatekeeper. Most kidney damage cases are associated with inflammation. In this review, we summarised the role of TRPA1 in neurogenic or non-neurogenic inflammation and in kidney disease, especially the non-neuronal TRPA1. In in vivo animal studies, TRPA1 prevented sepsis-induced or Ang-II-induced and ischemia-reperfusion renal injury by maintaining mitochondrial haemostasis or via the downregulation of macrophage-mediated inflammation, respectively. Renal tubular epithelial TRPA1 acts as an oxidative stress sensor to mediate hypoxia-reoxygenation injury in vitro and ischaemia-reperfusion-induced kidney injury in vivo through MAPKs/NF-kB signalling. Acute kidney injury (AKI) patients with high renal tubular TRPA1 expression had low complete renal function recovery. In renal disease, TPRA1 plays different roles in different cell types accordingly. These findings depict the important role of TRPA1 and warrant further investigation.


Asunto(s)
Enfermedades Renales/metabolismo , Canal Catiónico TRPA1/metabolismo , Animales , Humanos , Inflamación/metabolismo , Enfermedades Renales/patología , Neuronas/metabolismo , Transducción de Señal
20.
Ecotoxicol Environ Saf ; 215: 112161, 2021 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-33812202

RESUMEN

Recent studies have revealed that neutrophil extracellular traps (NETs) may contribute directly to the initiation of ulcerative colitis (UC), a typical inflammatory bowel disease (IBD) characterized by mucosal damage. Staphylococcal nuclease (SNase), a nonspecific phosphodiesterase, has a strong ability to degrade DNA. Here we investigate whether intestinal NET degradation with an oral preparation of SNase can ameliorate dextran sulfate sodium (DSS)-induced UC in mice. SNase encapsulated with calcium alginate (ALG-SNase) was formulated using crosslinking technology with sodium alginate and calcium chloride. ALG-SNase were orally administered to DSS-induced UC mice, and their therapeutic efficacy was evaluated. The expression of inflammatory cytokines and biomarkers of NETs was also assessed, as well as the intestinal permeability in mice. The results showed that ALG-SNase nanoparticles were successfully prepared and delivered to the colon of UC mice. In addition, oral administration of ALG-SNase nanoparticles decreased NET levels in the colon and effectively alleviated the clinical colitis index and tissue inflammation in UC mice. Moreover, the SNase nanoparticles reduced intestinal permeability and regulated the expression of proinflammatory cytokines. Furthermore, the markers of NETs were strongly correlated with the expression levels of tight junction proteins in colon tissue. In conclusion, our data showed that oral administration of ALG-SNase can effectively ameliorate colitis in UC mice via NET degradation and suggested SNase as a candidate therapy for the treatment of UC.


Asunto(s)
Trampas Extracelulares/metabolismo , Nucleasa Microcócica/administración & dosificación , Administración Oral , Animales , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/metabolismo , Citocinas/metabolismo , Modelos Animales de Enfermedad , Inflamación/inducido químicamente , Intestinos , Masculino , Ratones , Nucleasa Microcócica/metabolismo , Proteínas de Uniones Estrechas/metabolismo
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