RESUMEN
Osteosarcoma (OS) is the most frequent bone malignancy in humans. Previous evidence suggest that circ_0032463 is an oncogenic circular RNA (circRNA) in various cancers, including OS. However, the molecular mechanism of circ_0032463 involved in OS is still unclear. Circ_0032463, microRNA-145-5p (miR-145-5p), GDNF receptor alpha 1 (GFRA1), and Wilms tumor 1-associated protein (WTAP) levels were determined using real-time quantitative polymerase chain reaction (RT-qPCR). Cell proliferation, apoptosis, migration, invasion, and angiogenesis were analyzed using 5-ethynyl-2'-deoxyuridine (EdU), flow cytometry, transwell, and tube formation assays. Western blot analysis was performed to measure matrix metalloproteinase 2 (MMP2), MMP9, GFRA1, and WTAP protein levels. Binding between miR-145-5p and circ_0032463 or GFRA1 was confirmed using a dual-luciferase reporter and pull-down assay. The biological role of circ_0032463 on OS cell growth was also analyzed using a xenograft tumor model in vivo. Methylated RNA immunoprecipitation assay validated the interaction between WTAP and circ_0032463. Circ_0032463, GFRA1, and WTAP levels were increased, and miR-145-5p was decreased in OS tissues and cells. Circ_0032463 deficiency might hinder OS cell proliferation, migration, invasion, angiogenesis, and promote apoptosis in vitro. Mechanically, circ_0032463 worked as a miR-145-5p sponge to increase GFRA1 expression. Repression of circ_0032463 knockdown on tumor cell growth was proved in vivo. Besides, N6-methyladenosine (m6A) modification facilitates the biogenesis of circ_0032463. Taken together, m6A-mediated biogenesis of circ_0032463 facilitates OS cell malignant biological behavior partly via regulating the miR-145-5p/GFRA1 axis, suggesting a promising molecular marker for OS treatment.
Asunto(s)
Neoplasias Óseas , Receptores del Factor Neurotrófico Derivado de la Línea Celular Glial , MicroARNs , Osteosarcoma , ARN Circular , MicroARNs/genética , MicroARNs/metabolismo , Humanos , Osteosarcoma/genética , Osteosarcoma/patología , Osteosarcoma/metabolismo , ARN Circular/genética , ARN Circular/metabolismo , Receptores del Factor Neurotrófico Derivado de la Línea Celular Glial/genética , Receptores del Factor Neurotrófico Derivado de la Línea Celular Glial/metabolismo , Animales , Línea Celular Tumoral , Ratones , Neoplasias Óseas/genética , Neoplasias Óseas/metabolismo , Neoplasias Óseas/patología , Regulación Neoplásica de la Expresión Génica , Factores de Empalme de ARN/genética , Factores de Empalme de ARN/metabolismo , Ratones Desnudos , Masculino , Ratones Endogámicos BALB C , Proliferación Celular/genética , Progresión de la Enfermedad , Femenino , ARN Neoplásico/genética , ARN Neoplásico/metabolismo , Adenosina/análogos & derivados , Proteínas de Ciclo CelularRESUMEN
The natural history of metabolic dysfunction-associated steatotic liver disease (MASLD), previously referred to as non-alcoholic fatty liver disease (NAFLD), is complex and long. A minority of patients develop inflammation and risk progressive fibrosis that can result in cirrhosis. Progression to cirrhosis occurs in 3-5% of patients and often takes more than 20 years. This narrative review presents an update on the natural history of MASLD, discussing studies and risk estimates for progression to severe outcomes, such as decompensated cirrhosis or hepatocellular carcinoma. We highlight the dynamic progression of liver damage, how to identify patients whose disease progresses over time, and how risk factors might be mitigated to reduce the risk for disease progression.
Asunto(s)
Progresión de la Enfermedad , Cirrosis Hepática , Enfermedad del Hígado Graso no Alcohólico , Humanos , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/patología , Factores de Riesgo , Cirrosis Hepática/metabolismo , Cirrosis Hepática/complicaciones , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologíaRESUMEN
Purpose: This study aimed to investigate the proportion and risk factors of paroxysmal atrial fibrillation (AF) and atrial arrhythmias (AA) in patients hospitalized for acute exacerbation of chronic obstructive pulmonary disease (AECOPD) in Vietnam. Patients and Methods: A prospective observational study was conducted at two major hospitals in Hanoi, Vietnam, from January 2022 to January 2023. A total of 197 AECOPD patients were recruited. ECG and 24-hour Holter ECG were used to diagnose paroxysmal AF and AA. Results: The prevalence of paroxysmal AF and AA were 15.2% and 72.6%, respectively. Factors associated with a higher likelihood of paroxysmal AF included aging 75 years old and above (aOR = 3.15; 95% CI: 1.28 to 8.48), Premature atrial complex (PAC) with 500 or more (aOR = 3.81; 95% CI: 1.48 to 10.97) and severity of COPD as group C and D (aOR = 3.41; 95% CI: 1.28 to 10.50). For AA, aging 75 years old and above (aOR = 2.25; 95% CI: 1.28 to 5.20), smoking (aOR = 2.10; 95% CI: 1.07 to 4.23) and P wave dispersion (PWD) with 40 milliseconds or more (aOR = 3.04; 95% CI: 1.54 to 6.19) were associated with a higher likelihood of AA. Conclusion: Overall, our findings highlight the associated factors with the paroxysmal AF and AA among AECOPD patients. This underscores the importance of a multifaceted approach to risk assessment and management in this vulnerable population, focusing not only on respiratory symptoms but also on comprehensive cardiovascular evaluation and intervention.
Asunto(s)
Fibrilación Atrial , Progresión de la Enfermedad , Hospitalización , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/terapia , Anciano , Fibrilación Atrial/epidemiología , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/fisiopatología , Fibrilación Atrial/terapia , Masculino , Prevalencia , Femenino , Estudios Prospectivos , Persona de Mediana Edad , Factores de Riesgo , Vietnam/epidemiología , Hospitalización/estadística & datos numéricos , Factores de Edad , Medición de Riesgo , Anciano de 80 o más Años , Complejos Atriales Prematuros/epidemiología , Complejos Atriales Prematuros/diagnóstico , Complejos Atriales Prematuros/fisiopatología , Electrocardiografía AmbulatoriaRESUMEN
Introduction: neuromeningeal tuberculosis (NMT) is a significant public health challenge in Morocco because of its acute severity and high mortality rates. This study aims to comprehensively evaluate the epidemiological, clinical, therapeutic, and disease progression characteristics of NMT in the Kenitra province. Methods: a retrospective analysis was conducted on the medical records of patients diagnosed with NMT at the Diagnostic Center of Tuberculosis and Respiratory Diseases in Kenitra from 2014 to 2017. Results: among the 33 identified NMT cases, predominantly males (57.6%) were affected, with an age range of 4-76 years and a median age of 25 years. Extrapulmonary manifestations were prevalent, constituting 78.8% (n=26) of all cases, with meningeal localization in 45.5% (n=15) of confirmed cases. Furthermore, 9.1% (n=3) of cases were associated with unconfirmed cerebral tuberculosis (TB), and 12% (n=4) exhibited miliary TB. Familial transmission and comorbidities were identified as significant factors in disease progression. More than half of the patients received standardized antibacillary treatment during hospitalization, which lasted between 9 and 12 months. Treatment outcomes were generally positive (73%), but a 12% case fatality rate and 15% loss to follow-up were observed. Conclusion: this study highlights the complex clinical and public health challenges posed by NMT in Morocco. It emphasizes the need for improved health strategies that not only increase public awareness but also enhance the accessibility and quality of diagnostic services and treatment options.
Asunto(s)
Antituberculosos , Progresión de la Enfermedad , Índice de Severidad de la Enfermedad , Tuberculosis Meníngea , Humanos , Marruecos/epidemiología , Masculino , Femenino , Estudios Retrospectivos , Adolescente , Persona de Mediana Edad , Adulto , Niño , Adulto Joven , Anciano , Tuberculosis Meníngea/epidemiología , Tuberculosis Meníngea/diagnóstico , Tuberculosis Meníngea/tratamiento farmacológico , Preescolar , Antituberculosos/administración & dosificación , Resultado del Tratamiento , Hospitalización/estadística & datos numéricos , Tuberculosis Miliar/diagnóstico , Tuberculosis Miliar/epidemiología , Tuberculosis Miliar/tratamiento farmacológicoRESUMEN
In 30 patients (average age 38 ± 8 years, 77% male, 23% female) with intra-oral scans made at intake and after 3 years, tooth wear progression was measured. With the aid of GeoMagic to superimpose the scans, the maximum difference in height of 64 surfaces was measured per surface. A large variation was found in progression rates between patients, between various teeth in a single mouth, and between surfaces on a single tooth. Tooth wear progression rates are therefore highly individual and can even be very localized. Treatment must therefore be individualized, with an essential role for measuring tooth wear when deciding on the need for restorative treatment.
Asunto(s)
Desgaste de los Dientes , Humanos , Femenino , Masculino , Adulto , Progresión de la EnfermedadRESUMEN
PURPOSE: To determine the misclassification rate of the keratoconus percentage (KISA%) index efficacy in eyes with progressive keratoconus. METHODS: This was a retrospective case-control study of consecutive patients with confirmed progressive keratoconus and a contemporaneous normal control group with 1.00 diopters or greater regular astigmatism. Scheimpflug imaging (Pentacam HR) was obtained for all patients. KISA% index and inferior-superior (IS) values were obtained from the Pentacam topometric/keratoconus staging map. Receiver operating characteristic curves were generated to determine the area under the receiver operating characteristic curve (AUROC), sensitivity, and specificity values. RESULTS: There were 160 eyes from 160 patients evaluated, including 80 eyes from 80 patients with progressive keratoconus and 80 eyes from 80 control patients. There were 20 eyes (25%) with progressive keratoconus misclassified by the KISA% index, with 16 eyes (20%) of the progressive keratoconus cohort classified as normal (ie, KISA% < 60). There were 4 eyes (5%) with progressive keratoconus that would classify as having "normal topography" using the published criteria for very asymmetric ectasia with normal topography of KISA% less than 60 and IS value less than 1.45. All controls had a KISA% index value of less than 15. The optimal cut-off value to distinguish cohorts was 15.31 (AUROC = 0.972, 93.75% sensitivity). KISA% index values of 60 and 100 achieved low sensitivity (80% and 73.75%, respectively). CONCLUSIONS: The KISA% index misclassified a significant proportion of eyes with progressive keratoconus as normal. Although highly specific for clinical keratoconus, the KISA% index lacks sensitivity, does not effectively discriminate between normal and abnormal topography, and thus should not be used in large data analysis or artificial intelligence-based modeling. [J Refract Surg. 2024;40(9):e614-e624.].
Asunto(s)
Topografía de la Córnea , Progresión de la Enfermedad , Queratocono , Curva ROC , Humanos , Queratocono/clasificación , Queratocono/diagnóstico , Estudios Retrospectivos , Topografía de la Córnea/métodos , Masculino , Femenino , Adulto , Estudios de Casos y Controles , Adulto Joven , Córnea/patología , Córnea/diagnóstico por imagen , Sensibilidad y Especificidad , Agudeza Visual/fisiología , Adolescente , Área Bajo la Curva , Persona de Mediana Edad , Errores DiagnósticosRESUMEN
The second part of the literature review on the application of artificial intelligence (AI) methods for screening, diagnosing, monitoring, and treating glaucoma provides information on how AI methods enhance the effectiveness of glaucoma monitoring and treatment, presents technologies that use machine learning, including neural networks, to predict disease progression and determine the need for anti-glaucoma surgery. The article also discusses the methods of personalized treatment based on projection machine learning methods and outlines the problems and prospects of using AI in solving tasks related to screening, diagnosing, and treating glaucoma.
Asunto(s)
Inteligencia Artificial , Glaucoma , Aprendizaje Automático , Redes Neurales de la Computación , Humanos , Glaucoma/diagnóstico , Glaucoma/fisiopatología , Glaucoma/terapia , Progresión de la Enfermedad , Diagnóstico por Computador/métodosRESUMEN
Rhegmatogenous retinal detachment (RRD) is a severe disease of the visual organ that is one of the leading causes of blindness worldwide. Without surgical treatment, RRD almost always leads to vision loss and blindness. Surgical treatment in the early stages of the disease reduces the risk of blindness. This article analyzes scientific publications reflecting the issues of prognosis and prevention of RRD. Literature analysis showed that there are few prognostic matrices in ophthalmology in general, and specifically related to RRD. Most prognostic matrices for RRD are aimed at preventing its recurrence and predicting the development or progression of peripheral vitreochorioretinal dystrophy in the operated or fellow eye. Building a prognostic matrix for the risk of occurrence and development of such a serious disease as RRD in adults will allow early prediction, enabling surgical treatment in the shortest possible time and positively influencing the functional outcome of treatment.
Asunto(s)
Recurrencia , Desprendimiento de Retina , Desprendimiento de Retina/etiología , Desprendimiento de Retina/cirugía , Desprendimiento de Retina/diagnóstico , Humanos , Pronóstico , Progresión de la Enfermedad , Medición de Riesgo/métodos , Factores de RiesgoRESUMEN
This meta-analysis investigated efficacy of dapagliflozin as adjunctive therapy for patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) stages 2-5. A systematic search was conducted of selected databases for randomised controlled trials that reported the mean change in estimated glomerular filtration rate (eGFR) and urine albumin-creatinine ratio (UACR) from baseline. Out of 1,682 identified studies, 9 trials comprising 13,057 patients were included. A pooled estimate of 5 studies indicated that dapagliflozin did not affect eGFR; however, in 2 studies, it significantly reduced chronic eGFR decline compared to placebo (mean difference [MD] ± 2.74; 95% confidence interval [CI]: 1.55, 3.92; P <0.00001). Additionally, a pooled estimate of 4 studies showed that dapagliflozin significantly reduced UACR (MD -23.99%; 95% CI: -34.82--13.15; P <0.0001; I2 = 0%). Therefore, long-term use of dapagliflozin significantly attenuates eGFR decline and reduces albuminuria in patients with T2DM and CKD.
Asunto(s)
Compuestos de Bencidrilo , Diabetes Mellitus Tipo 2 , Glucósidos , Insuficiencia Renal Crónica , Humanos , Glucósidos/uso terapéutico , Glucósidos/farmacología , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/complicaciones , Compuestos de Bencidrilo/uso terapéutico , Compuestos de Bencidrilo/farmacología , Insuficiencia Renal Crónica/tratamiento farmacológico , Insuficiencia Renal Crónica/fisiopatología , Progresión de la Enfermedad , Tasa de Filtración Glomerular/efectos de los fármacos , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Inhibidores del Cotransportador de Sodio-Glucosa 2/farmacología , Femenino , MasculinoRESUMEN
BACKGROUND: Folate has an important role in the functioning of the musculoskeletal system, including modulation of inflammation, immunity, cartilage regeneration, prevention of osteoporosis, and maintenance of muscle strength, but evidence on the association between folate intake and knee pain, functional scores, and radiographic progression in patients with knee osteoarthritis (OA) is still limited. METHODOLOGY: Our population-based cohort was extracted from the osteoarthritis initiative (OAI), focusing on individuals with prevalent radiographic knee OA (with a Kellgren-Lawrence score ≥2). Folate consumption was determined using the food frequency questionnaire. Data regarding the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores and radiographic readings were collected over 48 months. We analyzed the compiled data using generalized additive mixed models. RESULTS: Our cohort consisted of 1472 OA patients (626 men and 846 women, mean [SD] age 62.35 [8.92]). At the 48-month follow-up, we observed a significant correlation between higher folate intake and a slower progression of knee pain and functional scores, as evidenced by a statistically significant decrease in the WOMAC total score, WOMAC pain subscale score, and WOMAC function/disability subscale score (p < .05). The fully adjusted models estimated a reduction of -0.028 points per 50 µg/1000 kcal of daily folate intake on the WOMAC pain subscale, -0.117 points on the WOMAC function subscale, and -0.160 points on the total WOMAC scale. Furthermore, our nonparametric fit analysis suggested that a higher intake of folate might decelerate the radiographic progression of OA. Stratified analyses indicated that an increase in folate consumption might particularly benefit men, older adults, overweight and obese individuals, and those with a higher dietary fiber intake. CONCLUSION: Higher folate intake is correlated with improved knee function and reduced pain in patients with knee OA and might deter the radiographic progression of OA. The benefits appear to be more pronounced in men, older adults, overweight and obese individuals, and those with a higher dietary fiber intake.
Asunto(s)
Artralgia , Progresión de la Enfermedad , Ácido Fólico , Articulación de la Rodilla , Osteoartritis de la Rodilla , Dimensión del Dolor , Humanos , Osteoartritis de la Rodilla/diagnóstico por imagen , Osteoartritis de la Rodilla/fisiopatología , Masculino , Femenino , Persona de Mediana Edad , Anciano , Ácido Fólico/administración & dosificación , Artralgia/fisiopatología , Artralgia/diagnóstico , Articulación de la Rodilla/diagnóstico por imagen , Articulación de la Rodilla/fisiopatología , Factores de Tiempo , Radiografía , Evaluación de la DiscapacidadRESUMEN
The progression of vitiligo is unpredictable, emphasizing the need to identify periods of activity early for tailored treatment. Confetti-like depigmentation, hypochromic areas/borders and Koebner's phenomenon are clinical visible signs associated with disease activity in vitiligo. However, their true clinical significance requires further investigation using standardized scoring systems. In the present study, the Vitiligo Signs of Activity Score (VSAS) and the Vitiligo Disease Activity Score (VDAS) were applied to assess disease activity signs and disease progression over time, respectively. Individuals with at least one disease activity sign had a 76.9% likelihood of having active vitiligo. The simultaneous presence of multiple signs or their appearance across body locations increased the likelihood to 94% and 87.1%, respectively. Patients with no disease activity signs had a 60.3% likelihood of having stable disease. This research provides an important nuance about the disease activity signs in vitiligo, which may help guide disease management. The risk of active disease increases when at least two types of vitiligo activity signs are present, or when they are present on different body locations. However, the absence of vitiligo activity signs does not rule out active vitiligo.
Asunto(s)
Progresión de la Enfermedad , Vitíligo , Vitíligo/diagnóstico , Humanos , Femenino , Masculino , Adulto , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Adulto Joven , Índice de Severidad de la Enfermedad , AdolescenteRESUMEN
OBJECTIVE: Purpose of this research was to examine the onset, progression and wear rates of dental erosion in an established mouse model. MATERIAL AND METHODS: Dental erosion in mice was experimentally induced, and the acidic effects of cola drink on their teeth after 2, 4 and 6-weeks were closely analysed by scanning electron microscopy. The tooth height and enamel or dentin loss were established. Results: The dental erosion on the molars showed clear progression from 2 to 6 weeks. By the 2-week mark, a significant portion of enamel was already eroded, revealing the dentin on the lingual cusps. When adjusted for attritional wear, molars exposed to cola for 2 weeks showed a 35% drop in lingual tooth height compared to controls (533 µm vs. 818 µm). At 4 and 6 weeks, the cola-exposed group continued to display decreased lingual tooth heights by 40% (476 µm vs. 799 µm) and 43% (440 µm vs. 767 µm), respectively. CONCLUSION: This study revealed significant acidic effects of cola drink on mouse molars as early as 2 weeks. These findings highlight the challenge of monitoring dental erosion clinically and underscore the importance of early preventive and intervention measures.
Asunto(s)
Modelos Animales de Enfermedad , Progresión de la Enfermedad , Erosión de los Dientes , Animales , Erosión de los Dientes/etiología , Erosión de los Dientes/patología , Ratones , Microscopía Electrónica de Rastreo , Bebidas Gaseosas/efectos adversos , Diente Molar , Masculino , Esmalte Dental/efectos de los fármacos , Esmalte Dental/patologíaRESUMEN
This article is meant to serve as a reference for radiologists, orthopedic surgeons, and other physicians to enhance their understanding of progressive collapsing foot deformity, also known as adult acquired flat foot deformity. Pathophysiology, imaging findings, especially on MRI and 3-dimensional MRI are discussed with relevant illustrations so that the readers can apply these principles in their practice for better patient managements.
Asunto(s)
Pie Plano , Imagenología Tridimensional , Imagen por Resonancia Magnética , Humanos , Imagen por Resonancia Magnética/métodos , Adulto , Pie Plano/diagnóstico por imagen , Deformidades Adquiridas del Pie/diagnóstico por imagen , Deformidades Adquiridas del Pie/etiología , Progresión de la EnfermedadRESUMEN
BACKGROUNDS: F-box protein 45 (FBXO45) has been implicated in the progression of several diseases. Whether FBXO45 is involved in the development of bladder cancer remains unclear. Thus, this study focused on the effect of FBXO45 on the malignant progression of bladder cancer cells. METHODS: FBXO45 small-interference fragment was transfected into RT4 and 5637 cells by liposome-mediated transfection, and the knockdown efficiency of FBXO45 was verified by Western blot assay. The growth rate between FBXO45 knockdown cell lines and control cell lines was compared by counting kit 8 and plate cloning experiments. The motility of bladder cancer cells was observed via the Transwell test and Wound healing test. The effects of FBXO45 silencing on apoptosis and cell division were confirmed by flow cytometry. Western blot assay was performed to determine the function of FBXO45 knockdown on key proteins of cell apoptosis and the ERK/Cyclin D1/CDK4 pathway. RESULTS: After FBXO45 knockdown, the proliferation of bladder cancer cells was blocked (p < 0.01), and the migration and invasion abilities were reduced (p < 0.01). FBXO45 knockdown reduced the number of S-phase cells (RT4, p < 0.01; 5637, p < 0.05) and enhanced the apoptotic rate (p < 0.01). FBXO45 knockdown decreased the levels of p-ERK1/2, CDK4 and Cyclin D1 (p < 0.01). CONCLUSIONS: This study revealed that FBXO45 plays a carcinogenic role in bladder cancer via the ERK/Cyclin D1/CDK4 pathway, which provides a reference for the clinical treatment of patients with bladder cancer.
Asunto(s)
Ciclina D1 , Quinasa 4 Dependiente de la Ciclina , Progresión de la Enfermedad , Proteínas F-Box , Técnicas de Silenciamiento del Gen , Neoplasias de la Vejiga Urinaria , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/metabolismo , Humanos , Quinasa 4 Dependiente de la Ciclina/metabolismo , Quinasa 4 Dependiente de la Ciclina/genética , Ciclina D1/metabolismo , Ciclina D1/genética , Proteínas F-Box/genética , Proteínas F-Box/metabolismo , Sistema de Señalización de MAP Quinasas , Células Tumorales Cultivadas , Línea Celular Tumoral , Proliferación CelularRESUMEN
Acute on Chronic Liver Failure (ACLF) is an unfavorable form of cirrhotic disease progression, distinguished from decompensated cirrhosis by a very high short-term mortality associated with damage to one or more organs. The pathophysiology is based on an intense systemic inflammatory reaction, the triggering factor of which can be identified (infection, toxic agent, etc.) in around two thirds of cases. The analogy with sepsis has enabled us to derive prognostic scores linked to organ damage, and thus to better guide these patients, who most often require close monitoring. Treatment remains limited and relies on support for the affected organs. Given the poor prognosis of these patients, attitude discussions should also be part of early management.
L'Acute on Chronic Liver Failure (ACLF) est une forme d'évolution défavorable de la maladie cirrhotique se distinguant de la cirrhose décompensée par une mortalité à court terme très élevée liée à une atteinte d'un ou plusieurs organes. La physiopathologie repose sur une réaction inflammatoire systémique, dont le facteur déclenchant peut être mis en évidence (infection, toxique, etc.) dans environ deux tiers des cas. L'analogie avec le sepsis a permis d'établir des scores pronostiques liés aux atteintes d'organes et ainsi de mieux orienter ces patients nécessitant le plus souvent une surveillance rapprochée. Le traitement reste limité et repose sur le soutien des organes atteints. Au vu du pronostic sombre de ces patients, des discussions d'attitude devraient également faire partie de la prise en charge précoce.
Asunto(s)
Insuficiencia Hepática Crónica Agudizada , Cirrosis Hepática , Humanos , Insuficiencia Hepática Crónica Agudizada/diagnóstico , Insuficiencia Hepática Crónica Agudizada/terapia , Insuficiencia Hepática Crónica Agudizada/etiología , Cirrosis Hepática/complicaciones , Pronóstico , Progresión de la EnfermedadRESUMEN
The intricate interplay between Homeobox genes, long non-coding RNAs (lncRNAs), and the development of malignancies represents a rapidly expanding area of research. Specific discernible lncRNAs have been discovered to adeptly regulate HOX gene expression in the context of cancer, providing fresh insights into the molecular mechanisms that govern cancer development and progression. An in-depth comprehension of these intricate associations may pave the way for innovative therapeutic strategies in cancer treatment. The HOX gene family is garnering increasing attention due to its involvement in immune system regulation, interaction with long non-coding RNAs, and tumor progression. Although initially recognized for its crucial role in embryonic development, this comprehensive exploration of the world of HOX genes contributes to our understanding of their diverse functions, potentially leading to immunology, developmental biology, and cancer research discoveries. Thus, the primary objective of this review is to delve into these aspects of HOX gene biology in greater detail, shedding light on their complex functions and potential therapeutic applications.
Asunto(s)
Progresión de la Enfermedad , Regulación Neoplásica de la Expresión Génica , Genes Homeobox , Sistema Inmunológico , Neoplasias , ARN Largo no Codificante , Humanos , Neoplasias/genética , Neoplasias/inmunología , ARN Largo no Codificante/genética , Genes Homeobox/genética , Sistema Inmunológico/metabolismo , AnimalesRESUMEN
INTRODUCTION: Ultrasound changes in the cross-sectional area of the median nerve (CSAmn) could be of interest as biomarkers in patients with amyotrophic lateral sclerosis (ALS). METHODS: Eighty-four ALS patients (51 men [60.7%]; mean 62.0 [SD 11.46] years old) and forty-six controls (27 men [58.7%]; mean 59.9 [SD 8.08] years old) of two different cohorts were recruited between September 2013 and February 2018. The CSAmn was measured bilaterally in each cohort, by two different examiners with two different ultrasound machines (one in each cohort). Its association with clinical variables (disease duration, muscle strength, disability, progression rate and tracheostomy-free survival) was assessed. RESULTS: The CSAmn was smaller in patients than in controls, and the study cohort did not influence its values. A mild correlation between the strength of the wrist flexor and the CSAmn was found. In the multivariable analysis, the probability of this association being true was 90%. In the cox regression, both a faster progression rate and a larger CSAmn independently predicted poor survival (HR=4.29, [Cr.I95%: 2.71-6.80], p<0.001; and HR=1.14, [Cr.I95%: 1.03-1.25], p=0.01), after adjusting by age, body mass index, bulbar onset, and diagnostic delay. CONCLUSIONS: The CSAmn is an easy to assess biomarker that seems reliable and reproducible. Our data also suggest that it could act as a progression and prognostic biomarker in ALS patients. Longitudinal studies with repeated measures are warranted to confirm its usefulness in the clinical practice.
Asunto(s)
Esclerosis Amiotrófica Lateral , Biomarcadores , Nervio Mediano , Ultrasonografía , Humanos , Masculino , Persona de Mediana Edad , Femenino , Nervio Mediano/diagnóstico por imagen , Pronóstico , Anciano , Progresión de la Enfermedad , Estudios de CohortesRESUMEN
Apelin, a bioactive peptide that serves as an endogenous ligand for the apelin receptor (APJ), is overexpressed in various types of cancers and contributes to cancer cell proliferation, viability, migration, angiogenesis, and metastasis, as well as immune deviation. Noncoding RNAs (ncRNAs) regulate gene expression, and there is growing evidence suggesting a bidirectional crosstalk between ncRNAs (including long noncoding RNAs [lncRNAs], circular RNAs [circRNAs], and microRNAs [miRNAs]) and apelin in cancers. Certain miRNAs can directly target the apelin and inhibit its expression, thereby suppressing tumor growth. It has been indicated that miR-224, miR-195/miR-195-5p, miR-204-5p, miR-631, miR-4286, miR-637, miR-4493, and miR-214-3p target apelin mRNA and influence its expression in prostate cancer, lung cancer, esophageal cancer, chondrosarcoma, melanoma, gastric cancer, glioma, and hepatocellular carcinoma (HCC), respectively. Moreover, circ-NOTCH1, circ-ZNF264, and lncRNA BACE1-AS upregulate apelin expression in gastric cancer, glioma, and HCC, respectively. On the other hand, apelin has been shown to regulate the expression of certain ncRNAs to affect tumorigenesis. It was revealed that apelin affects the expression of circ_0000004/miR-1303, miR-15a-5p, and miR-106a-5p in osteosarcoma, lung cancer, and prostate cancer, respectively. This review explains a bidirectional interplay between ncRNAs and apelin in cancers to provide insights concerning the molecular mechanisms underlying this crosstalk and potential implications for cancer therapy.
Asunto(s)
Apelina , Neoplasias , Humanos , Apelina/metabolismo , Apelina/genética , Neoplasias/metabolismo , Neoplasias/patología , Neoplasias/genética , ARN no Traducido/metabolismo , ARN no Traducido/genética , MicroARNs/metabolismo , MicroARNs/genética , Progresión de la Enfermedad , ARN Largo no Codificante/metabolismo , ARN Largo no Codificante/genética , AnimalesRESUMEN
Following a comprehensive patient examination, including the assessment of periodontal and peri-implant diseases as well as considering the patient's needs, a pretherapeutic prognosis for each tooth and implant is given. Teeth and implants with a secure pretherapeutic prognosis require simple procedures and may be regarded as secure abutments for function and with a doubtful pretherapeutic prognosis usually need a comprehensive therapy. Such teeth and implants must be brought into the category with a secure prognosis by means of additional therapy such as endodontic, restorative, and surgical procedures. Teeth and implants with a hopeless pretherapeutic prognosis should be extracted/explanted during the initial phase of cause-related therapy (i.e., infection control). For example, teeth with vertical root fracture or unrestorable caries and implants with mobility or unrestorable malposition fall into the category of hopeless units. The primary goal of periodontal and peri-implant therapy should be to arrest disease progression. The latest consensus statement highlights that periodontitis can be successfully controlled and treated teeth can be retained for life. Nevertheless, for patients with uncontrolled contributing factors, the endpoints might not always be achievable, and low disease activity may be an acceptable therapeutic goal. Similarly, the management of peri-implantitis frequently requires surgical intervention following nonsurgical therapy due to incomplete treatment outcomes. Different surgical modalities can be effective and lead to significant improvement; however, achieving complete resolution of peri-implantitis is challenging, not always predictable, and can depend on multiple baseline factors. Therefore, this review aims at summarising available evidence on the rationale for incorporating systemic, lifestyle-related, clinical, and radiographic prognostic factors into treatment planning of patients diagnosed with periodontal and peri-implant diseases.
Asunto(s)
Implantes Dentales , Planificación de Atención al Paciente , Humanos , Pronóstico , Enfermedades Periodontales/terapia , Periimplantitis/terapia , Progresión de la EnfermedadRESUMEN
Background: Ferroptosis, as a novel form of programmed cell death, plays a crucial role in the occurrence and development of bladder cancer (BCa). However, the regulatory mechanisms of ferroptosis in the tumor microenvironment (TME) of BCa remain to be elucidated. Methods: Based on single-cell RNA (scRNA) transcriptomic data of BCa, we employed non-negative matrix factorization (NMF) dimensionality reduction clustering to identify novel ferroptosis-related cell subtypes within the BCa TME, aiming to explore the biological characteristics of these TME cell subtypes. Subsequently, we conducted survival analysis and univariate Cox regression analysis to explore the prognostic significance of these cell subtypes. We investigated the relationship between specific subtypes and immune infiltration, as well as their implications for immunotherapy. Finally, we discovered a valuable and novel biomarker for BCa, supported by a series of in vitro experiments. Results: We subdivided cancer-associated fibroblasts (CAFs), macrophages, and T cells into 3-5 small subpopulations through NMF and further explored the biological features. We found that ferroptosis played an important role in the BCa TME. Through bulk RNA-seq analysis, we further verified that ferroptosis affected the progression, prognosis, and immunotherapy response of BCa by regulating the TME. Especially ACSL4+CAFs, we found that high-level infiltration of this CAF subtype predicted worse prognosis, more complex immune infiltration, and less response for immunotherapy. Additionally, we found that this type of CAF was associated with cancer cells through the PTN-SDC1 axis, suggesting that SDC1 may be crucial in regulating CAFs in cancer cells. A series of in vitro experiments confirmed these inferences: SDC1 promoted the progression of BCa. Interestingly, we also discovered FTH1+ macrophages, which were closely related to SPP1+ macrophages and may also be involved in the regulation of BCa TME. Conclusion: This study revealed the significant impact of ferroptosis on bladder cancer TME and identified novel ferroptosis-related TME cell subpopulations, ACSL4+CAFs, and important BCa biomarker SDC1.