RESUMEN
Background/Aims: Ulcerative colitis (UC) is an incurable, relapsing-remitting inflammatory disease that increases steadily. Mucosal healing has become the primary therapeutic objective for UC. Nevertheless, endoscopic assessments are invasive, expensive, time-consuming, and inconvenient. Therefore, it is crucial to develop a noninvasive predictive model to monitor endoscopic activity in patients with UC. Methods: Clinical data of 198 adult patients with UC were collected from January 2016 to August 2022 at Huadong Hospital, China. Results: Patients with UC were randomly divided into the training cohort (70%, n=138) and the validation cohort (30%, n=60). The receiver operating characteristic curve value for the training group was 0.858 (95% confidence interval [CI], 0.781 to 0.936), whereas it was 0.845 (95% CI, 0.731 to 0.960) for the validation group. The calibration curve employed the Hosmer-Lemeshow test (p>0.05) to demonstrate the consistency between the predicted and the actual probabilities in the nomogram of these two groups. The decision curve analysis validated that the nomogram had clinical usefulness. Conclusions: The nomogram, which incorporated activated partial thromboplastin time, fecal occult blood test, ß2-globulin level, and fibrinogen degradation products, served as a prospective tool for evaluating UC activity in clinical practices.
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Colitis Ulcerosa , Colonoscopía , Nomogramas , Humanos , Colitis Ulcerosa/diagnóstico , Femenino , Masculino , Adulto , Persona de Mediana Edad , Colonoscopía/estadística & datos numéricos , Colonoscopía/métodos , Medición de Riesgo/métodos , Curva ROC , China , Valor Predictivo de las Pruebas , Sangre OcultaRESUMEN
The age-related pro-inflammatory state, discovered and called 'inflammaging' by Franceschi et al. (2000) plays an important role in the pathogenesis of age-related chronic diseases. A substantial body of data established that inflammaging is accompanied by a '2-fold to 4-fold' increase in plasma levels of pro-inflammatory mediators in healthy elderly people, when compared to the healthy adult population. This review focuses on the pre-inflammaging phase, here we reported as 'cold-inflammaging', a state where plasma levels of cytokines are slightly increased, but below the lower limit of 2-fold increase established for inflammaging. Slightly altered cytokine levels by innate immunity are known to be associated with homeostasis imbalances, this functional pleiotropy of cytokines as signal transducers, have a physiological counterpart, representing an adaptive process aimed at restoring (or achieving a new) homeostatic stability. If a dyshomeostatic state persists, the cytokine response by innate immunity increases and becomes a driver of inflammaging. A scenario where cytokines are characterised as major players in homeostasis imbalances at the beginning (cold-inflammaging) and then in chronic low-grade pro-inflammatory-state (inflammaging). Other important drivers of inflammaging are cellular senescence with its senescence-associated secretory phenotype, the altered gut microbiota, and the age-related dysregulation in the production of endogenous molecular waste (Garb-aging). The main purpose of this review being to thoroughly investigate each step of the pathway from cold-inflammaging to overt-inflammaging, because aging, cold-inflammaging, overt-inflammaging and the pathogenesis of age-related diseases have been shown to share some established basic pillars of geroscience that largely converge on inflammaging.
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Envejecimiento , Inflamación , Envejecimiento/fisiología , Citocinas/metabolismo , Homeostasis , Humanos , Inflamación/metabolismo , FenotipoRESUMEN
The coronavirus disease 2019 (COVID-19) is a new infectious respiratory disease, which has caused a pandemic that has become the world's leading public health emergency, threatening people of all ages worldwide, especially the elderly. Complications of COVID-19 are closely related to an upregulation of the inflammatory response revealed by the pro-inflammatory profile of plasma cytokines (to the point of causing a cytokine storm), which is also a contributing cause of the associated coagulation disorders with venous and arterial thromboembolisms, causing multiple organ dysfunction and failure. In severe fulminant cases of COVID-19, there is an activation of coagulation and consumption of clotting factors leading to a deadly disseminated intravascular coagulation (DIC). It is well established that human immune response changes with age, and also that the pro-inflammatory profile of plasma cytokines is upregulated in both healthy and diseased elderly people. In fact, normal aging is known to be associated with a subclinical, sterile, low-grade, systemic pro-inflammatory state linked to the chronic activation of the innate immune system, a phenomenon known as "inflammaging". Inflammaging may play a role as a condition contributing to the co-occurrence of the severe hyper-inflammatory state (cytokine storm) during COVID-19, and also in other severe infections (sepsis) in older people. Moreover, we must consider the impact of inflammation on coagulation due to the crosstalk between inflammation and coagulation. The systemic inflammatory state and coagulation disorders are closely related, a phenomenon that here we call "coagul-aging" (Giunta S.). In this review, we discuss the various degrees of inflammation in older adults after being infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the adverse effects of aging on the inflammatory response and coagulation system. It is important to note that although there is no gender difference in susceptibility to COVID-19 infection, however, due to differences in angiotensin-converting enzyme 2 (ACE2) expression, innate immunity, and comorbidities, older men exhibit more severe disease and higher mortality than older women. There are currently no FDA-approved specific antiviral drugs that can be used against the virus. Therapies used in patients with COVID-19 consist of remdesivir, dexamethasone, low-molecular-weight heparin, in addition to monoclonal antibodies against the spike protein of SARS-CoV-2 in the early phase of the disease. Future pharmacological research should also consider targeting the possible role of the underlying scenario of inflammaging in healthy older people to prevent or mitigate disease complications. It is worth mentioning that some specific cytokine antagonists and traditional Chinese medicine preparations can reduce the elderly's inflammatory state.
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Trastornos de la Coagulación Sanguínea , COVID-19 , Anciano , Envejecimiento , Síndrome de Liberación de Citoquinas , Femenino , Humanos , Masculino , SARS-CoV-2RESUMEN
Previous studies on the longevity effect of pyrroloquinoline quinine (PQQ) on nematode worms have revealed that PQQ can enhance the antioxidant capacity of nematode worms, thus extending the lifespan of the worms. The induction and development of cellular senescence are closely connected with inflammatory reactions. The aim of this study was to determine the effect of PQQ and ageing factors on senescent cells. To this end, we cultivated human embryonic lung fibroblasts in nutrient solution with or without tumour necrosis factor-alpha (TNF-α) to establish an inflammaging model in vitro. The cells were preincubated with or without PQQ to determine if PQQ had any anti-inflammaging effect. More senescent cells were detected with the addition of TNF-α than without (P < .01). The ratio of senescent cells to non-senescent cells in the TNF-α group was greater than that in the control group (P < .01). When cells were preincubated with PQQ prior to TNF-α treatment, there were fewer senescent cells than those in the control group, which was not pretreated with PQQ (P < .05). The same tendency was noted with regard to p21, p16, and Jagged1. In summary, we used TNF-α, a well-known pro-inflammatory cytokine associated with inflammaging, to establish an in vitro inflammaging model and provided evidence that PQQ delays TNF-α -induced cellular senescence and has anti-inflammaging properties.