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Probiotics are not only a food supplement, but they have shown great potential in their nutritional, health and therapeutic effects. To maximize the beneficial effects of probiotics, it is commonly achieved by adding prebiotics. Prebiotics primarily comprise indigestible carbohydrates, specific peptides, proteins, and lipids, with oligosaccharides being the most extensively studied prebiotics. However, these rapidly fermenting oligosaccharides have many drawbacks and can cause diarrhea and flatulence in the body. Hence, the exploration of new prebiotic is of great interest. Besides oligosaccharides, protein hydrolysates have been demonstrated to enhance the expression of beneficial properties of probiotics. Consequently, this paper outlines the mechanism underlying the action of protein hydrolysates on probiotics, as well as the advantageous impacts of proteins hydrolysates derived from various food sources on probiotics. In addition, this paper also reviews the currently reported biological activities of protein hydrolysates. The aim is a theoretical basis for the development and implementation of novel prebiotics.
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Androgenetic alopecia (AGA) is the most common type of progressive hair loss in both men and women that severely reduces life quality and affects patients' self-esteem. Due to the shortcomings of traditional therapeutic formulations (e.g., topical minoxidil and oral finasteride), such as low bioavailability, frequent dosing, and significant side effects, there is an urgent need to develop a safe and effective strategy for AGA treatment. Here, we report a water-soluble microneedle (MN) patch integrated with biodegradable minoxidil (MXD)-loaded microspheres for long-acting AGA treatment with reduced administration frequency and improved patient compliance. When the patch pierces the skin, the MNs rapidly dissolve and deliver MXD-encapsulated polylactic-co-glycolic acid (PLGA) microspheres into the skin, which, subsequently act as drug reservoirs for the sustained release of the therapeutics for over 2 weeks. Additionally, the application of the MN patch provided a mechanical stimulation on mouse skin, which was also helpful for hair regrowth. Compared with the topical MXD solutions that have been commercialized on the market and require daily application, the long-acting MN patch contains a much lower drug amount and shows a similar or superior hair regeneration effect in AGA mice while only requiring monthly or weekly administration. These encouraging results suggest a simple, safe, and effective strategy for long-acting hair regeneration in clinics.
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Alopecia , Minoxidil , Femenino , Ratones , Animales , Minoxidil/farmacología , Minoxidil/uso terapéutico , Microesferas , Administración Tópica , Alopecia/tratamiento farmacológico , Alopecia/inducido químicamente , Cabello , Resultado del TratamientoRESUMEN
The increasing incidence of thyroid cancer (TC) cannot be fully explained by overdiagnosis. Metabolic syndrome (Met S) is highly prevalent due to the modern lifestyle, which can lead to the development of tumors. This review expounds on the relationship between Met S and TC risk, prognosis and its possible biological mechanism. Met S and its components were associated with an increased risk and aggressiveness of TC, and there were gender differences in most studies. Abnormal metabolism places the body in a state of chronic inflammation for a long time, and thyroid-stimulating hormones may initiate tumorigenesis. Insulin resistance has a central role assisted by adipokines, angiotensin II, and estrogen. Together, these factors contribute to the progression of TC. Therefore, direct predictors of metabolic disorders (e.g., central obesity, insulin resistance and apolipoprotein levels) are expected to become new markers for diagnosis and prognosis. cAMP, insulin-like growth factor axis, angiotensin II, and AMPK-related signaling pathways could provide new targets for TC treatment.
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Background: The gene mutation of isocitrate dehydrogenase-1 (IDH1) is commonly found in LGG and some GBM patients and usually carries tumor protein 53 (TP53) mutations. However, the underlying mechanisms on both mutations of glioma patients in IDH1 and TP53 are still unclear. Aim: To find the potential target markers in GBM and LGG patients with IDH1 and TP53 mutation.Method: A total of 1122 glioma patients from The Cancer Genome Atlas were enrolled and divided as wild-type (without IDH1 and TP53 mutations) or both mutant (both IDH1 and TP53 mutations). The data of clinicopathological characteristics, mRNA, mutations, and copy number alteration were analyzed. Results: IDH1 and TP53 mutations, not gene expression, affect the survival probability of GBM and LGG patients, which might be related to neuron function, immune function, tumor invasion, and metastasis. The effects of the selected gene (EMILIN3, SAA1, VSTM2A, HAMP, IFT80, and CHIC2) on glioma patients could be regulated by IDH1 and TP53 mutations and had a higher survival possibility in these patients. Conclusions: The selected genes in GBM and LGG patients with IDH1 and TP53 mutations could be a potential prognosis marker in the future.
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Neoplasias Encefálicas , Glioma , Humanos , Neoplasias Encefálicas/genética , Genómica , Glioma/genética , Isocitrato Deshidrogenasa/genética , Mutación/genética , PronósticoRESUMEN
Background: Hypertension (HTN) is known to increase the risk of thyroid cancer. However, few studies have explored the association between HTN and the prognostic factors of papillary thyroid cancer (PTC). Methods: We retrospectively evaluated 2838 PTC patients treated with surgery at our center between January 2017 and September 2020. The association between both HTN and antihypertensive drug use and the clinicopathological features of the PTC patients was analyzed. The odds ratios (ORs) were estimated using both univariate and multivariate logistic regression models, which were adjusted for the patients' age, sex, and thyroid-stimulating hormone level. Results: A total of 2838 patients were enrolled in this study, including 409 patients with HTN. In the multivariate analysis, HTN was associated with larger tumor size [OR = 1.51, 95% confidence interval (CI): 1.10-2.07], lymph node metastasis (OR = 1.43, 95% CI: 1.02-1.99), and higher tumor stages (OR = 1.79, 95% CI: 1.12-2.86). There was no statistical difference between females >40 years of age and any pathological features, while a positive association was observed between older males and larger tumors (OR = 1.87, 95% CI: 1.01-3.45), and lymph node metastasis (OR = 2.01, 95% CI: 1.08-3.73). No statistical difference was found in the effects of taking alone calcium channel blockers, angiotensin-converting enzyme inhibitors/angiotensin II-receptor blockers, and their combination on the pathological features of PTC. Conclusion: PTC patients with HTN, particularly males of age >40, tend to have invasive features. Common antihypertension therapy appears to exert no effect on the pathological characteristics of these patients.
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Carcinoma Papilar , Carcinoma , Hipertensión , Neoplasias de la Tiroides , Masculino , Femenino , Humanos , Cáncer Papilar Tiroideo/complicaciones , Metástasis Linfática , Carcinoma Papilar/patología , Estudios Retrospectivos , Antihipertensivos/uso terapéutico , Bloqueadores de los Canales de Calcio , Angiotensina II , Carcinoma/patología , Carcinoma/cirugía , Neoplasias de la Tiroides/complicaciones , Neoplasias de la Tiroides/epidemiología , Neoplasias de la Tiroides/patología , Hipertensión/complicaciones , Hipertensión/epidemiología , Inhibidores de la Enzima Convertidora de Angiotensina , Tirotropina , Factores de RiesgoRESUMEN
Exploring the potential functions of nonconserved residues on the outer side of α-helices and systematically optimizing them are pivotal for their application in protein engineering. Based on the evolutionary structural conservation analysis of GH5_5 cellulases, a practical molecular improvement strategy was developed. Highly variable sites on the outer side of the α-helices of the GH5_5 cellulase from Aspergillus niger (AnCel5A) were screened, and 14 out of the 34 highly variable sites were confirmed to exert a positive effect on the activity. After the modular combination of the positive mutations, the catalytic efficiency of the mutants was further improved. By using CMC-Na as the substrate, the catalytic efficiency and specific activity of variant AnCel5A_N193A/T300P/D307P were approximately 2.0-fold that of AnCel5A (227 ± 21 versus 451 ± 43 ml/s/mg and 1,726 ± 19 versus 3,472 ± 42 U/mg, respectively). The half-life (t1/2) of variant AnCel5A_N193A/T300P/D307P at 75°C was 2.36 times that of AnCel5A. The role of these sites was successfully validated in other GH5_5 cellulases. Computational analyses revealed that the flexibility of the loop 6-loop 7-loop 8 region was responsible for the increased catalytic performance. This work not only illustrated the important role of rapidly evolving positions on the outer side of the α-helices of GH5_5 cellulases but also revealed new insights into engineering the proteins that nature left as clues for us to find. IMPORTANCE A comprehensive understanding of the residues on the α-helices of the GH5_5 cellulases is important for catalytic efficiency and stability improvement. The main objective of this study was to use the evolutionary conservation and plasticity of the TIM-barrel fold to probe the relationship between nonconserved residues on the outer side of the α-helices and the catalytic efficiency of GH5_5 cellulases by conducting structure-guided protein engineering. By using a four-step nonconserved residue screening strategy, the functional role of nonconserved residues on the outer side of the α-helices was effectively identified, and a variant with superior performance and capability was constructed. Hence, this study proved the effectiveness of this strategy in engineering GH5_5 cellulases and provided a potential competitor for industrial applications. Furthermore, this study sheds new light on engineering TIM-barrel proteins.
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Celulasa , Celulasas , Aspergillus niger/genética , Aspergillus niger/metabolismo , Catálisis , Celulasa/metabolismo , Celulasas/metabolismo , MutaciónRESUMEN
Immune checkpoint inhibitors (ICIs) are a group of drugs employed in the treatment of various types of malignant tumors and improve the therapeutic effect. ICIs blocks negative co-stimulatory molecules, such as programmed cell death gene-1 (PD-1) and its ligand (PD-L1) and cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), reactivating the recognition and killing effect of the immune system on tumors. However, the reactivation of the immune system can also lead to the death of normal organs, tissues, and cells, eventually leading to immune-related adverse events (IRAEs). IRAEs involve various organs and tissues and also cause thyroid dysfunction. This article reviews the epidemiology, clinical manifestations, possible pathogenesis, and management of ICIs-related thyroid dysfunction.
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Inhibidores de Puntos de Control Inmunológico/metabolismo , Enfermedades de la Tiroides/diagnóstico , Enfermedades de la Tiroides/inmunología , Enfermedades de la Tiroides/terapia , Anciano , Anciano de 80 o más Años , Antígeno B7-H1/metabolismo , Antígeno CTLA-4/metabolismo , Progresión de la Enfermedad , Femenino , Predisposición Genética a la Enfermedad , Antígenos HLA/biosíntesis , Homeostasis , Humanos , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Sistema Inmunológico , Inmunoterapia/métodos , Ligandos , Masculino , Persona de Mediana Edad , Receptor de Muerte Celular Programada 1/metabolismo , Linfocitos T/citología , Enfermedades de la Tiroides/epidemiología , Glándula Tiroides/fisiopatologíaRESUMEN
Berberine (BBR) is a plant secondary metabolite that has been used in photodynamic therapy (PDT) in the last few decades. The present review aimed to discuss the research progress of BBR-mediated photodynamic actions. The following key words were searched in several databases: 'Berberine' combined with 'photodynamic therapy', 'sonodynamic therapy (SDT)', 'ultraviolet', 'reactive oxygen' and 'singlet oxygen'. The results demonstrated that both type I and type II reactions participated in the photodynamic progression of BBR derivatives. In addition, the photochemical characteristics of BBR derivatives were affected by the polarity, pH and O2 content of solvents. DNA binding increases the lifespan of the photoexcited BBR state and generation of singlet oxygen (1O2). The chemical properties of substituents in different positions of the BBR skeleton are pivotal for its photochemical properties, particularly the methylenedioxy group at the C-2 and C-3 positions. BBR is a promising agent for mediating both PDT- and SDT-treated diseases, particularly in tumors. However, further studies are required to validate their biological effects. In addition, the molecular mechanisms underlying the antitumor effects of BBR-PDT remain unclear and warrant further investigation. The structural modification and targeted delivery of BBR have made it possible to broaden its applications; however, experimental verification is required. Overall, BBR acts as a sensitizer for PDT and has promising development prospects.
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Objectives: A significant proportion of discharged COVID-19 patients still have some symptoms. Traditional Chinese medicine (TCM) has played an important role in the treatment of COVID-19, but whether it is helpful for discharged patients is still unknown. The aim of this study was to retrospectively analyze the impacts of TCM treatment on the convalescents of COVID-19. Methods: A total of 372 COVID-19 convalescents from February 21 to May 3 in Shenzhen, China were retrospectively analyzed, 291 of them accepted clinically examined at least once and 191 convalescents accepted TCM. Results: After retrospective analysis of the clinical data of convalescents accepted TCM treatment or not, we found that the white blood cell count, as well as serum interleukin-6 and procalcitonin decreased in TCM group. Serum γ-glutamyl transpeptidase was significantly decreased, while prealbumin and albumin increased in TCM group. Red blood cell, hemoglobin, and platelet count increased in TCM group. The mechanisms of TCM treatment might be the overall regulations, including balanced immune response, improved hematopoiesis and coagulation systems, enhanced functions of liver and heart, increased nutrient intake and lipid metabolism. Conclusions: This study suggested that TCM treatment would be beneficial for discharged COVID-19 patients. However, long-term medical observation and further study with randomized trial should be done to confirm this result. Besides, the potential molecular mechanisms of TCM treatment should be further revealed.
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COVID-19/rehabilitación , Convalecencia , Medicamentos Herbarios Chinos/administración & dosificación , COVID-19/sangre , COVID-19/diagnóstico , Hospitales de Aislamiento/estadística & datos numéricos , Humanos , Estudios Retrospectivos , SARS-CoV-2/aislamiento & purificación , Resultado del TratamientoRESUMEN
Objective: The aim of this study was to observe the liver function recovery of COVID-19 patients after discharge. Patients and Methods: A total of 253 discharged COVID-19 patients in Shenzhen city, China were selected. The clinical characteristics of these patients were assessed. A 2-month follow-up and laboratory hematology test were performed to examine the status of patients' liver function. Results: Patients combined with liver diseases, especially fatty liver, are more likely to progress to severe condition (P<0.05). Patients in severe condition and those with liver diseases have higher rates of liver injuries during hospitalization, characterized by a significant increase in alanine aminotransferase (ALT) and aspartate aminotransferase (AST, P<0.01). The ALT, AST/ALT, gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), total protein (TP), albumin (ALB), and A/G levels showed significant differences in comparison with the control group (P<0.05, and P<0.001); and the outlier ratio of A/G, ALT, GGT and ALP of patients remained abnormal higher within 14 days after discharge (P<0.001). Liver injuries of COVID-19 patients may be related to the epidemiological characteristics, clinical indexes, basic diseases, symptoms, drug treatment during hospitalization and the complications. Indicators of liver function were correlated with cardiac function, renal function, thyroid function, lipid metabolism, glucose metabolism, immune index, leukocyte, erythrocyte, hemoglobin and platelet related indexes. The outlier ratio of TP, ALB and GLB remained extremely low throughout the follow-up period; the outlier ratio of ALT, AST and GGT decreased below 10% from a high level at 40 days after discharged. However, the outlier ratio of A/G, AST/ALT and ALP remained high during the follow-up period. Conclusions: Abnormal liver function might indicate worse recovery of COVID-19 patients. Changes in liver function should be emphasized during long-term follow-up of COVID-19 patients after hospital discharge; the necessity of employing appropriate interventions for liver function repair should be emphasized.
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COVID-19/complicaciones , Insuficiencia Hepática/virología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , COVID-19/fisiopatología , Niño , Preescolar , Estudios Transversales , Femenino , Estudios de Seguimiento , Humanos , Lactante , Pruebas de Función Hepática , Masculino , Persona de Mediana Edad , Recuperación de la Función , Adulto JovenRESUMEN
Objectives: Research on recovering COVID-19 patients could be helpful for containing the pandemic and developing vaccines, but we still do not know much about the clinical features, recovery process, and antibody reactions during the recovery period. Methods: We retrospectively analysed the epidemiological information, discharge summaries, and laboratory results of 324 patients. Results: In all, 15 (8.62%) patients experienced chest distress/breath shortness, where 8 of the 15 were severely ill. This means severely ill patients need an extended amount of time to recover after discharge; next, 20 (11.49%) patients experienced anxiety and 21 (12.07%) had headache/insomnia and a small fraction of them complained of anosmia/ageusia, indicating that these patients need treatment for mental and psychological health issues. Regarding the re-positive patients, their CT and laboratory test results showed no obvious evidence of illness progress or infectivity but a high anti-SARS-CoV-2 antibody expression. Conclusion: Recovered COVID-19 patients need psychological and physiological care and treatment, re-positivity can occur in any person, but juveniles, females, and patients with mild/moderate existing symptoms have higher rates of re-positivity, While there is no evidence that turning re-positive has an impact on their infectivity, but it still alerted us that we need differentiate them in the following managements.
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COVID-19/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Ageusia , Anosmia , COVID-19/psicología , COVID-19/rehabilitación , COVID-19/virología , Niño , Preescolar , China/epidemiología , Femenino , Estudios de Seguimiento , Humanos , Lactante , Masculino , Persona de Mediana Edad , Recurrencia , Estudios Retrospectivos , SARS-CoV-2/aislamiento & purificación , Adulto JovenRESUMEN
The BMI1 protein, a member of the PRC1 family, is a well recognised transcriptional suppressor and has the capability of maintaining the self-renewal and proliferation of tissue-specific stem cells. Numerous studies have established that BMI1 is highly expressed in a variety of malignant cancers and serves as a key regulator in the tumorigenesis process. However, our understanding of BMI1 in terminally differentiated organs, such as the heart, is relatively nascent. Importantly, emerging data support that, beyond the tumor, BMI1 is also expressed in the heart tissue and indeed exerts profound effects in various cardiac pathological conditions. This review gives a summary of the novel functions of BMI1 in the heart, including BMI1-positive cardiac stem cells and BMI1-mediated signaling pathways, which are involved in the response to various cardiac pathological stimuli. Besides, we summarize the recent progress of BMI1 in some novel and rapidly developing cardiovascular therapies. Furtherly, we highlight the properties of BMI1, a therapeutic target proved effective in cancer treatment, as a promising target to alleviate cardiovascular diseases.
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Miocardio/metabolismo , Complejo Represivo Polycomb 1/genética , Complejo Represivo Polycomb 1/metabolismo , Animales , Biomarcadores , Enfermedades Cardiovasculares/tratamiento farmacológico , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/metabolismo , Transformación Celular Neoplásica/genética , Transformación Celular Neoplásica/metabolismo , Susceptibilidad a Enfermedades , Descubrimiento de Drogas , Regulación de la Expresión Génica , Humanos , Terapia Molecular Dirigida , Neoplasias/tratamiento farmacológico , Neoplasias/etiología , Neoplasias/metabolismo , Neoplasias/patología , Especificidad de Órganos , Complejo Represivo Polycomb 1/antagonistas & inhibidores , Transducción de Señal , Células Madre/metabolismoRESUMEN
Cardiac hypertrophy, a stereotypic cardiac response to increased workload, ultimately progresses to severe contractile dysfunction and uncompensated heart failure without appropriate intervention. Sustained cardiac overload inevitably results in high energy consumption, thus breaking the balance between mitochondrial energy supply and cardiac energy demand. In recent years, accumulating evidence has indicated that mitochondrial dysfunction is implicated in pathological cardiac hypertrophy. The significant alterations in mitochondrial energetics and mitochondrial proteome composition, as well as the altered expression of transcripts that have an impact on mitochondrial structure and function, may contribute to the initiation and progression of cardiac hypertrophy. This article presents a summary review of the morphological and functional changes of mitochondria during the hypertrophic response, followed by an overview of the latest research progress on the significant modulatory roles of mitochondria in cardiac hypertrophy. Our article is also to summarize the strategies of mitochondria-targeting as therapeutic targets to treat cardiac hypertrophy.
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Macrophages are integral components of the mammalian heart that show extensive expansion in response to various internal or external stimuli. After the onset of sustained pressure overload (PO), the accumulation of cardiac macrophages through local macrophage proliferation and monocyte migration has profound effects on the transition to cardiac hypertrophy and remodeling. In this review, we describe the heterogeneity and diversity of cardiac macrophages and summarize the current understanding of the important roles of macrophages in PO-induced cardiac remodeling. In addition, the possible mechanisms involved in macrophage modulation are also described. Finally, considering the significant effects of cardiac macrophages, we highlight their emerging role as therapeutic targets for alleviating pathological cardiac remodeling after PO.
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Macrófagos/inmunología , Miocardio/inmunología , Remodelación Ventricular/inmunología , Animales , Humanos , Presión VentricularRESUMEN
The aim of the present study was to explore the antitumor effects of sinoporphyrin sodium (DVDMS)mediated photodynamic therapy (PDT) and sonodynamic therapy (SDT) in glioma, and to reveal the underlying mechanisms. The uptake of DVDMS by U118 MG cells was detected by flow cytometry (FCM). A 630nm semiconductor laser and 1MHz ultrasound were used to perform PDT and SDT, respectively. Cell proliferation and apoptosis were evaluated using the Cell Counting Kit8 assay, FCM and Hoechst 33258 staining, respectively. Western blot analysis was used to detect protein expression and phosphorylation levels. BALB/c nude mice were used to establish a xenograft model of U118 MG cells. DVDMS was injected intravenously and PDT and SDT were performed 24 h later. An in vivo imaging system was used to evaluate the fluorescence of DVDMS, to measure tumor sizes, and to evaluate the therapeutic effects. The uptake of DVDMS by U118 MG cells was optimal after 4 h. PDT and SDT following DVDMS injection significantly inhibited the proliferation and increased apoptosis of glioma cells in vitro (P<0.05, P<0.01) respectively. In vivo, the fluorescence intensity of DVDMS was lower in the PDT and SDT groups compared with the DVDMS group, while tumor cell proliferation and weight were lower in the PDT and SDT groups than in the control group (P<0.05, P<0.01). However, there was no significant difference when laser, ultrasound or DVDMS were applied individually, compared with the control group. Hematoxylin and eosin staining suggested that both PDT and SDT induced significant apoptosis and vascular obstruction in cancer tissues. DVDMSmediated PDT and SDT inhibited the expression levels of proliferating cell nuclear antigen (PCNA) and BclxL, increased cleaved caspase 3 levels, and decreased the protein phosphorylation of the PI3K/AKT/mTOR signaling pathway. Changes in the expression of PCNA, and BclxL and in the levels of cleavedcaspase 3 were partly reversed by NacetylLcysteine, a reactive oxygen species (ROS) scavenger. Similar results were obtained with FCM. DVDMSmediated PDT and SDT inhibited glioma cell proliferation and induced cell apoptosis in vitro and in vivo, potentially by increasing the generation of ROS and affecting protein expression and phosphorylation levels.
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Glioma/terapia , Fotoquimioterapia , Porfirinas/farmacología , Terapia por Ultrasonido , Animales , Apoptosis/efectos de los fármacos , Apoptosis/efectos de la radiación , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Proliferación Celular/efectos de la radiación , Terapia Combinada , Citometría de Flujo , Glioma/patología , Humanos , Láseres de Semiconductores/uso terapéutico , Ratones , Especies Reactivas de Oxígeno/metabolismo , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Cardiac remodeling is a common characteristic of almost all forms of heart disease, including cardiac infarction, valvular diseases, hypertension, arrhythmia, dilated cardiomyopathy and other conditions. It is not merely a simple outcome induced by an increase in the workload of cardiomyocytes (CMs). The remodeling process is accompanied by abnormalities of cardiac structure as well as disturbance of cardiac function, and emerging evidence suggests that a wide range of cells in the heart participate in the initiation and development of cardiac remodeling. Other than CMs, there are numerous noncardiomyocytes (non-CMs) that regulate the process of cardiac remodeling, such as cardiac fibroblasts and immune cells (including macrophages, lymphocytes, neutrophils, and mast cells). In this review, we summarize recent knowledge regarding the definition and significant effects of various non-CMs in the pathogenesis of cardiac remodeling, with a particular emphasis on the involved signaling mechanisms. In addition, we discuss the properties of non-CMs, which serve as targets of many cardiovascular drugs that reduce adverse cardiac remodeling.
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Fibroblastos/fisiología , Cardiopatías/patología , Sistema Inmunológico/citología , Miocardio/citología , Animales , HumanosRESUMEN
Recently, the recurrence of positive SARS-CoV-2 viral RNA in recovered COVID-19 patients is receiving more attention. Herein we report a cohort study on the follow-up of 182 recovered patients under medical isolation observation. Twenty (10.99%) patients out of the 182 were detected to be SARS-CoV-2 RNA positive (re-positives), although none showed any clinical symptomatic recurrence, indicating that COVID-19 responds well to treatment. Patients aged under 18 years had higher re-positive rates than average, and none of the severely ill patients re-tested positive. There were no significant differences in sex between re-positives and non-re-positives. Notably, most of the re-positives turned negative in the following tests, and all of them carried antibodies against SARS-CoV-2. This indicates that they might not be infectious, although it is still important to perform regular SARS-CoV-2 RNA testing and follow-up for assessment of infectivity. The findings of this study provide information for improving the management of recovered patients, and for differentiating the follow-up of recovered patients with different risk levels.
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Betacoronavirus/genética , Infecciones por Coronavirus/patología , Neumonía Viral/patología , ARN Viral/metabolismo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Antivirales/sangre , Betacoronavirus/inmunología , Betacoronavirus/aislamiento & purificación , COVID-19 , Niño , Preescolar , Estudios de Cohortes , Infecciones por Coronavirus/genética , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Pandemias , Neumonía Viral/genética , Recurrencia , Riesgo , SARS-CoV-2 , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
Thyroid cancers (TC) have increasingly been detected following advances in diagnostic methods. Risk stratification guided by refined information becomes a crucial step toward the goal of personalized medicine. The diagnosis of TC mainly relies on imaging analysis, but visual examination may not reveal much information and not enable comprehensive analysis. Artificial intelligence (AI) is a technology used to extract and quantify key image information by simulating complex human functions. This latent, precise information contributes to stratify TC on the distinct risk and drives tailored management to transit from the surface (population-based) to a point (individual-based). In this review, we started with several challenges regarding personalized care in TC, for example, inconsistent rating ability of ultrasound physicians, uncertainty in cytopathological diagnosis, difficulty in discriminating follicular neoplasms, and inaccurate prognostication. We then analyzed and summarized the advances of AI to extract and analyze morphological, textural, and molecular features to reveal the ground truth of TC. Consequently, their combination with AI technology will make individual medical strategies possible.
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Synovitis is an aseptic inflammation that leads to joint effusion, pain and swelling. As one of the main drivers of pathogenesis in osteoarthritis (OA), the presence of synovitis contributes to pain, incidence and progression of OA. In our previous study, DC32 [(9α,12α-dihydroartemisinyl) bis(2'-chlorocinnmate)], a dihydroartemisinin derivative, was found to have an antirheumatic ability via immunosuppression, but the effect of DC32 on synovitis has not been fully illuminated. In this study, we chose to evaluate the effect and mechanism of DC32 on attenuating synovial inflammation. Fibroblast-like synoviocytes (FLSs) of papain-induced OA rats were isolated and cultured. And DC32 significantly inhibited the invasion and migration of cultured OA-FLSs, as well as the transcription of IL-6, IL-1ß, CXCL12 and CX3CL1 in cultured OA-FLSs measured by qPCR. DC32 remarkably inhibited the activation of ERK and NF-κB pathway, increased the expression of Nrf2 and HO-1 in cultured OA-FLSs detected by western blot. DC32 inhibited the degradation and phosphorylation of IκBα which further prevented the phosphorylation of NF-κB p65 and the effect of DC32 could be relieved by siRNA for Nrf2. In papain-induced OA mice, DC32 significantly alleviated papain-induced mechanical allodynia, knee joint swelling and infiltration of inflammatory cell in synovium. DC32 upregulated the mRNA expression of Type II collagen and aggrecan, and downregulated the mRNA expression of MMP2, MMP3, MMP13 and ADAMTS-5 in the knee joints of papain-induced OA mice measured by qPCR. The level of TNF-α in the serum and secretion of TNF-α in the knee joints were also reduced by DC32 in papain-induced OA mice. In conclusion, DC32 inhibited the inflammatory response in osteoarthritic synovium through regulating Nrf2/NF-κB pathway and attenuated OA. In this way, DC32 may be a potential agent in the treatment of OA.
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Antirreumáticos/uso terapéutico , Artemisininas/uso terapéutico , Inflamación/tratamiento farmacológico , Osteoartritis/tratamiento farmacológico , Membrana Sinovial/inmunología , Sinoviocitos/fisiología , Animales , Movimiento Celular , Células Cultivadas , Citocinas/metabolismo , Modelos Animales de Enfermedad , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , FN-kappa B/metabolismo , Fosforilación , Ratas , Ratas Sprague-Dawley , Transducción de SeñalRESUMEN
Non-syndromic hearing loss (NSHL) is a common defect in humans. Variants of MARVELD2 at the DFNB49 locus have been shown to cause bilateral, moderate to profound NSHL. However, the role of MARVELD2 in NSHL susceptibility in the Chinese population has not been studied. Here we conducted a case-control study in an eastern Chinese population to profile the spectrum and frequency of MARVELD2 variants, as well as the association of MARVELD2 gene variants with NSHL. Our results showed that variants identified in the Chinese population are significantly different from those reported in Slovak, Hungarian, and Czech Roma, as well as Pakistani families. We identified 11 variants in a cohort of 283 NSHL cases. Through Sanger sequencing and bioinformatics analysis, we found that c.730G>A variant has detrimental effects in the eastern Chinese population, and may have relatively high correlation with NSHL pathogenicity.