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PURPOSE OF REVIEW: This review aims to provide a theoretical basis and insights for quercetin's clinical application in the prevention and treatment of osteoporosis (OP), analyzing its roles in bone formation promotion, bone resorption inhibition, anti-inflammation, antioxidant effects, and potential mechanisms. RECENT FINDINGS: OP, a prevalent bone disorder, is marked by reduced bone mineral density and impaired bone architecture, elevating the risk of fractures in patients. The primary approach to OP management is pharmacotherapy, with quercetin, a phytochemical compound, emerging as a focus of recent interest. This natural flavonoid exerts regulatory effects on bone marrow mesenchymal stem cells, osteoblasts, and osteoclasts and promotes bone health and metabolic equilibrium via anti-inflammatory and antioxidative pathways. Although quercetin has demonstrated significant potential in regulating bone metabolism, there is a need for further high-quality clinical studies focused on medicinal quercetin.
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Antioxidantes , Osteoporosis , Quercetina , Quercetina/uso terapéutico , Quercetina/farmacología , Humanos , Osteoporosis/tratamiento farmacológico , Antioxidantes/uso terapéutico , Antioxidantes/farmacología , Osteoclastos/efectos de los fármacos , Osteogénesis/efectos de los fármacos , Densidad Ósea/efectos de los fármacos , Antiinflamatorios/uso terapéutico , Resorción Ósea/tratamiento farmacológico , Osteoblastos/efectos de los fármacos , Células Madre Mesenquimatosas , Conservadores de la Densidad Ósea/uso terapéutico , Conservadores de la Densidad Ósea/farmacologíaRESUMEN
INTRODUCTION/AIMS: Descriptions of the clinical characteristics of anti-AChR-MuSK-LRP4 antibody-negative myasthenia gravis (triple-negative myasthenia gravis, TNMG) are lacking in the current literature. Therefore, we investigated the clinical characteristics of TNMG in Chinese patients. METHODS: We retrospectively analyzed 925 patients with MG registered in the Department of Neuroimmunology, Henan Institute of Medical and Pharmaceutical Sciences from January 2015 to March 2021. RESULTS: One hundred six patients diagnosed with TNMG were included in the study. The average age of onset was 32.4 y, with a male-to-female ratio of 1:1. The age of onset showed a bimodal distribution: 0-9 y and 40-49 y. Adult patients were more likely to have weakness of limb and bulbar muscles (p < .05). Thymic hyperplasia was found in 20.2% of the patients. Younger patients were more likely to relapse. The rate of adult early-onset myasthenia gravis reaching complete stable remission and pharmacological remission was 47.6%, and the prognosis was better than that in juvenile-onset myasthenia gravis (p = .019). Older age of onset was the only risk factor for the development of generalized TNMG from ocular TNMG (R = 1.046, p = .002, 95% confidence interval 1.017-1.077). DISCUSSION: This study showed that the clinical characteristics of patients with TNMG varied among the different age groups. Significant findings included a bimodal distribution of onset age, coexisting thymic hyperplasia, and a generally favorable prognosis.
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Miastenia Gravis , Hiperplasia del Timo , Adulto , Humanos , Masculino , Femenino , Receptores Colinérgicos , Estudios Retrospectivos , Proteínas Tirosina Quinasas Receptoras , Autoanticuerpos , Recurrencia Local de Neoplasia , Miastenia Gravis/diagnóstico , Miastenia Gravis/epidemiología , China/epidemiología , Proteínas Relacionadas con Receptor de LDLRESUMEN
Neurodegenerative diseases are a collective term for a large group of diseases caused by degenerative changes in nerve cells. Aging is the main risk factor for neurodegenerative diseases. The neurovascular unit(NVU) is the smallest functional unit of the brain, which regulates brain blood flow and maintains brain homeostasis. Accelerated aging of NVU cells directly impairs NVU function and leads to the occurrence of various neurodegenerative diseases. The intrinsic mechanisms of NVU cell aging are complex and involve oxidative stress damage, loss of protein homeostasis, DNA damage, mitochondrial dysfunction, immune inflammatory response, and impaired cellular autophagy. In recent years, studies have found that traditional Chinese medicine(TCM) can inhibit NVU aging through multiple pathways and targets, exerting a brain-protective effect. Therefore, this article aimed to provide a theoretical basis for further research on TCM inhibition of NVU cell aging and references for new drug development and clinical applications by reviewing its mechanisms of anti-aging, such as regulating relevant proteins, improving mitochondrial dysfunction, reducing DNA damage, lowering inflammatory response, antioxidant stress, and modulating cellular autophagy.
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Medicina Tradicional China , Enfermedades Neurodegenerativas , Humanos , Enfermedades Neurodegenerativas/tratamiento farmacológico , Encéfalo , Envejecimiento , Neuronas , Barrera HematoencefálicaRESUMEN
OBJECTIVE: The objective of this study was to evaluate the impact of single nucleotide polymorphisms (SNPs) in triggering receptor expressed on the myeloid cells 2 protein (TREM2) gene and their interaction with environmental factors and haplotypes on late-onset Alzheimer's disease (LOAD). METHODS: DNA was extracted from the whole blood of the participants and genotyped using PCR and followed by restriction fragment length polymorphism. The Hardy-Weinberg equilibrium test was used in the control group. Multivariate logistic regression analysis was used to determine the relationship between the 4 SNPs of the TREM2 gene and the risk of LOAD. Generalized multifactor dimensionality reduction was used to test the best interaction combination between SNPs and environmental factors. RESULTS: Logistic regression analysis showed that the T allele of rs75932628 and the T allele of rs2234253 were independently associated with increased risk of LOAD, and adjusted odds ratios (ORs) were 1.81 (1.271-2.35) and 1.59 (1.15-2.03), respectively. However, there was no significant association with LOAD for rs142232675 and rs143332484. We found a best model significantly associated with LOAD risk that consisted of rs75932628 and smoking, which scored 10/10 for both the sign test and cross-validation consistency (p = 0.012). Stratified analysis indicated that current smokers with rs75932628-CT/TT genotype have the highest LOAD risk compared to never smokers with rs75932628 - CC genotype, OR (95% confidence interval) = 2.73 (1.72-3.79). Haplotypes of rs75932628 and rs2234253 were analyzed using the SHEsis online software. However, no haplotype was found to be significantly associated with the risk of LOAD. CONCLUSIONS: The T allele of rs75932628 and the T allele of rs2234253 and interaction between rs75932628 and smoking were all correlated with increased risk of LOAD.
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Enfermedad de Alzheimer , Enfermedad de Alzheimer/genética , Pueblo Asiatico/genética , China/epidemiología , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Glicoproteínas de Membrana/genética , Polimorfismo de Nucleótido Simple , Receptores Inmunológicos/genéticaRESUMEN
Triple-negative breast cancer (TNBC) is a breast cancer subtype without targeted treatment options. Accumulating evidence has demonstrated the roles of circular RNAs in cancer. This study aimed to investigate the expression and function of circFAM64A in TNBC. The GSE101124 dataset from the GEO database was examined to identify the differentially expressed circular RNAs in TNBC. RT-qPCR and western blot analyses were performed to measure gene expression. TNBC cell proliferation, migration, invasion, and cell cycle were assessed using cell counting kit-8, EdU, flow cytometry, wound healing, and transwell invasion experiments. Bioinformatics analysis, RIP, RNA pulldown, and luciferase reporter assays were used to investigate the regulatory mechanism of circFAM64A. In this study, CircFAM64A expression was significantly upregulated in TNBC tissues and cells compared with normal tissues and cells. Overexpression of circFAM64A increased the proliferative, migratory, and invasive capacities of TNBC cells and promoted cell cycle progression. Mechanistically, circFAM64A acted as a molecular sponge for miR-149-5p, and miR-149-5p directly targeted the Cdc10-dependent transcript 1 (CDT1) 3'UTR. Moreover, the high expression of CDT1 is associated with a poor prognosis in patients with breast cancer. Rescue experiments demonstrated that circFAM64A sponged miR-149-5p to increase CDT1 expression, thereby promoting cellular processes in TNBC. Overall, CircFAM64A plays an oncogenic role in TNBC by interacting with miR-149-5p to increase CDT1 expression.
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Péptidos y Proteínas de Señalización Intracelular/genética , MicroARNs , Proteínas Nucleares/genética , Neoplasias de la Mama Triple Negativas , Proteínas de Ciclo Celular/metabolismo , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica/genética , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Neoplasias de la Mama Triple Negativas/genéticaRESUMEN
This study aims to systematically evaluate the efficacy and safety of Shuxuetong Injection in the treatment of stroke in progressive. Randomized controlled trials of Shuxuetong Injection in the treatment of stroke in progressive were searched from CNKI, Wanfang, VIP, CMB, PubMed and EMbase. After strict literature screening, data extraction and quality evaluation, a total of 22 articles were included for analysis by RevMan 5.3. The Meta-analysis showed that Shuxuetong Injection combined with conventional treatment was superior to the conventional treatment alone in the major outcome indicators including effective rate(RR=1.27, 95%CI[1.20, 1.33], Z=9.18, P<0.000 01), deterioration rate(RR=0.38, 95%CI[0.22, 0.68], Z=3.31, P=0.000 9), NIHSS scores(MD=-3.89, 95%CI[-4.34,-3.43], Z=16.83, P<0.000 01), CSS scores(MD=-5.59, 95%CI[-6.42,-4.76], Z=13.20, P<0.000 01) and activity of daily living scores(MD=12.02, 95%CI[10.31, 13.72], Z=13.83, P<0.000 01), mortality during treatment was not increased(RR=0.40, 95%CI[0.13, 1.26], Z=1.56, P=0.12). Moreover, Shuxuetong Injection combined with conventional treatment further reduced the secondary outcome indicators including fibrinogen(MD=-0.35, 95%CI[-0.58,-0.13], Z=3.09, P=0.002), triglyceride(MD=-0.38, 95%CI[-0.67,-0.10], Z=2.65, P=0.008), low density lipoprotein cholesterol(MD=-0.72, 95%CI[-0.83,-0.61], Z=12.64, P<0.000 01), serum hypersensitive C-reactive protein(MD=-4.41, 95%CI[-6.96,-1.86], Z=3.38, P=0.000 7), and interleukin-6(MD=-5.43, 95%CI[-6.91,-3.96], Z=7.22, P<0.000 01). GRADE evaluation results showed that the major outcome indicators had low quality of evidence. Shuxuetong Injection in the treatment of stroke in progressive can improve the clinical effective rate, reduce the deterioration rate, improve the neurological function and activity of daily living, down-regulate the levels of fibrinogen, triglyceride, low density lipoprotein cholesterol and alleviate the inflammatory response. Although most studies have reported no adverse reactions, there are selective reports. The safety of Shuxuetong Injection needs to be further verified by more high-quality randomized controlled trial.
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Medicamentos Herbarios Chinos , Accidente Cerebrovascular , Medicamentos Herbarios Chinos/uso terapéutico , Humanos , Inyecciones , Accidente Cerebrovascular/tratamiento farmacológico , Resultado del TratamientoRESUMEN
In this study, the potential of specific Circular RNAs (circRNAs) as novel peripheral blood biomarkers for myasthenia gravis (MG) was explored. We analyzed circRNAs in the peripheral blood of three normal controls and three MG patients using RNA microarray. Candidate circRNAs were validated in three independent cohorts by Quantitative Real-time polymerase chain reaction (qPCR). Eleven differentially expressed circRNAs were initially identified and four were confirmed in the first independent cohort. Hsa_circ_0076490 and hsa-circ_5333-4 had the largest areas under the curve (AUCs) of the receiver operating characteristics (ROC) and were validated in the second cohort. In the third cohort, hsa-circRNA5333-4 had a larger AUC: 0.864 (95% confidence interval [CI] = 0.801-0.928, P < 0.001), a stronger correlation with the Quantitative Myasthenia Gravis Score (qMG): r = 0.505 (P < 0.001) and was correlated with gender and acetylcholine receptor antibody levels (P < 0.05). So hsa-circRNA5333-4 represents a novel biomarker for the diagnosis and monitoring of MG.
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ARN Circular/sangre , ARN Circular/química , Albúmina Sérica Humana/química , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Niño , Preescolar , Estudios de Cohortes , Femenino , Regulación de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Miastenia Gravis/sangre , Miastenia Gravis/genética , Curva ROC , Reproducibilidad de los Resultados , Adulto JovenRESUMEN
In the present study, to delve into the effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) combined with temozolomide (TMZ) on high-grade glioma cells and related mechanism, six cases of high-grade glioma cells from patient's tumor tissues were cultured. 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di- phenytetrazoliumromide 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di- phenytetrazoliumromide (MTT) assay was performed to detect cell proliferation and toxicity. Flow cytometry was performed to ascertain cell cycle and apoptosis rate. To detect the expressions of O6-methylguanine-DNA methyltransferase (MGMT) methylation status and MGMT protein, respectively, specific PCR and immunofluorescence were performed. According to the results of MTT assay, compared with the results of control group, GM-CSF group exhibited enhanced cell viability in varying degrees. In three cases of cells (MGMT gene methylation), the combination group [(67.67 ± 1.16), (68.13 ± 1.06), (68.42 ± 1.73)] had noticeably lower cell viability than the corresponding TMZ group [(90.00 ± 1.73), (82.33 ± 1.53), (82.67 ± 2.11)] (P < 0.01). Nevertheless, the two groups showed no significant difference in another three cases (MGMT gene unmethylated) (P > 0.05). In combination group, the apoptosis rate of the MGMT methylation cells was higher than that in the corresponding TMZ group (P < 0.01), which is consistent with MTT assay results. In all six cases of primary glioma cells, the fraction of cells in G1 phase of GM-CSF-treated group was noticeably down-regulated and was up-regulated in S phase (P < 0.01). GM-CSF could induce high-grade glioma cells to rapidly enter the cell cycle, thereby enhancing the lethal effect of TMZ on glioma cells with MGMT gene promoter methylation. However, this effect is not ideal on glioma cells with MGMT unmethylation.
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Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Astrocitoma/tratamiento farmacológico , Neoplasias del Sistema Nervioso Central/tratamiento farmacológico , Glioblastoma/tratamiento farmacológico , Factor Estimulante de Colonias de Granulocitos y Macrófagos/farmacología , Temozolomida/farmacología , Astrocitoma/enzimología , Astrocitoma/genética , Astrocitoma/patología , Ciclo Celular/efectos de los fármacos , Neoplasias del Sistema Nervioso Central/enzimología , Neoplasias del Sistema Nervioso Central/genética , Neoplasias del Sistema Nervioso Central/patología , Metilación de ADN , Metilasas de Modificación del ADN/biosíntesis , Metilasas de Modificación del ADN/genética , Enzimas Reparadoras del ADN/biosíntesis , Enzimas Reparadoras del ADN/genética , Sinergismo Farmacológico , Glioblastoma/enzimología , Glioblastoma/genética , Glioblastoma/patología , Factor Estimulante de Colonias de Granulocitos y Macrófagos/administración & dosificación , Humanos , Inmunohistoquímica , Clasificación del Tumor , Regiones Promotoras Genéticas , Temozolomida/administración & dosificación , Células Tumorales Cultivadas , Proteínas Supresoras de Tumor/biosíntesis , Proteínas Supresoras de Tumor/genéticaRESUMEN
IgA plays an important role in mucosal immunity against infectious pathogens; however, the molecular mechanism of IgA secretion in response to infection remains largely unknown, particularly in Mycoplasma spp. In this study, we found that the levels of IgA in the peripheral blood serum, bronchoalveolar lavage fluid, nasal mucosa, trachea, hilar lymph nodes, and lung tissues of pigs increased significantly after infection with Mycoplasma hyopneumoniae Furthermore, IgA and CD11c were detected in the lungs and hilar lymph nodes by immunohistochemical analysis, and colocalization of these two markers indicates that CD11c+ cells play an important role in IgA mucosal immunity induced by M. hyopneumoniae To investigate the regulatory mechanism of IgA, we separated mouse dendritic cells (DCs) from different tissues and mouse macrophages from the lungs and then cultured mouse B cells together with either DCs or macrophages in vitro In the mouse lung-DC/B (LDC/B) cell coculture, IgA secretion was increased significantly after the addition of whole-cell lysates of M. hyopneumoniae The expression of both Toll-like receptor 2 (TLR2) and TLR4 was also upregulated, as determined by mRNA and protein expression analyses, whereas no obvious change in the expression of TLR3 and TLR7 was detected. Moreover, the IgA level decreased to the same as the control group when TLR2 or TLR4 was inhibited instead of TLR8 or TLR7/9. In conclusion, M. hyopneumoniae can stimulate the response of IgA through TLR2 and TLR4 in a mouse LDC/B cell coculture model, and the coculture model is an ideal tool for studying the IgA response mechanism, particularly that with Mycoplasma spp.
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Formación de Anticuerpos , Inmunoglobulina A/inmunología , Mycoplasma hyopneumoniae/inmunología , Neumonía Porcina por Mycoplasma/inmunología , Receptor Toll-Like 2/metabolismo , Receptor Toll-Like 4/metabolismo , Animales , Linfocitos B/inmunología , Células Dendríticas/inmunología , Macrófagos/inmunología , Ratones , Modelos Teóricos , PorcinosRESUMEN
The metabolic inhibition (MI) test is a classic test for the identification of mycoplasmas, used for measuring the growth-inhibiting antibodies directed against acid-producing mycoplasmas, although their mechanism still remains obscure. To determine the major antigens involved in the immune killing of Mycoplasma bovis, we used a pulldown assay with anti-M. bovis antibodies as bait and identified nine major antigens. Among these antigens, we performed the MI test and determined that the growth of M. bovis could be inhibited effectively in the presence of complement by antibodies against specifically membrane protein P81 or UgpB in the presence of complement. Using a complement killing assay, we demonstrated that M. bovis can be killed directly by complement and that antibody-dependent complement-mediated killing is more effective than that by complement alone. Complement lysis and scanning electron microscopy results revealed M. bovis rupture in the presence of complement. Together, these results suggest that the metabolic inhibition of M. bovis is antibody-dependent complement-mediated killing. This study provides new insights into mycoplasma killing by the complement system and may guide future vaccine development studies for the treatment of mycoplasma infection. Furthermore, our findings also indicate that mycoplasmas may be an appropriate new model for studying the lytic activity of membrane attack complex (MAC).
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Anticuerpos Antibacterianos/inmunología , Proteínas del Sistema Complemento/inmunología , Proteínas de la Membrana/inmunología , Infecciones por Mycoplasma/veterinaria , Mycoplasma bovis/inmunología , Animales , Bovinos , Complejo de Ataque a Membrana del Sistema Complemento/inmunología , Microscopía Electrónica de Rastreo , Infecciones por Mycoplasma/inmunología , ConejosRESUMEN
Dysfunctional cell proliferation and death are the foundation of the malignant biological characteristics of cancers. In this study, we discovered that ZEB1 was positively correlated with hTERT in breast invasive ductal carcinoma samples at both the mRNA and protein levels. Further, our in vitro study in breast cancer cell lines confirmed that ZEB1 regulates hTERT expression at the mRNA and protein levels; thus, hTERT promotes or inhibits telomerase activity, and telomere length is either protected or reduced. Finally, we verified that ZEB1, which mostly functions as a transcriptional repressor, can recruit the co-activator YAP to enhance the transcriptional activation of hTERT. Fascinatingly, instead of acting on E-boxes, the ZEB1/YAP complex tends to function as a transcriptional activator by binding with sequences potentially located in the hTERT promoter. Consequently, our research revealed a new ZEB1-hTERT signaling pathway involved in cell proliferation regulation that has never before been illuminated in breast cancer.
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Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Telomerasa/metabolismo , Homeobox 1 de Unión a la E-Box con Dedos de Zinc/metabolismo , Proliferación Celular , Células Cultivadas , Femenino , Regulación Enzimológica de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Humanos , Invasividad Neoplásica , Células Tumorales Cultivadas , Regulación hacia ArribaRESUMEN
INTRODUCTION: Myasthenia gravis (MG) occurs globally, and many studies have indicated that there are regional differences in epidemiology, biomarkers, and prognosis of MG. METHODS: A total of 478 patients with MG who visited hospitals in the Henan Province between January 2010 and February 2014 were included. Age, gender, age at onset, serum antibody, thymus pathology, treatment information, and Myasthenia Gravis Foundation of America (MGFA) classification were assessed. RESULTS: Compared with previous reports from other areas, we found some differences in MG patients from Henan. The proportion of childhood MG in our study was lower than other reports of Oriental patients with MG. There seems to be an association between onset age, muscle involvement, and acetylcholine receptor antibody levels. Thymectomy improved the symptoms in 78.5% of thymectomy-treated patients. CONCLUSIONS: These differences are likely related to geographical, environmental, and ethnic differences. Understanding these differences will help us to define more specific treatment.
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Autoanticuerpos/inmunología , Debilidad Muscular , Miastenia Gravis/epidemiología , Receptores Colinérgicos/inmunología , Timo/patología , Adolescente , Corticoesteroides/uso terapéutico , Adulto , Distribución por Edad , Edad de Inicio , Anciano , Anciano de 80 o más Años , Azatioprina/uso terapéutico , Niño , Preescolar , China/epidemiología , Inhibidores de la Colinesterasa/uso terapéutico , Estudios de Cohortes , Femenino , Humanos , Inmunoglobulinas Intravenosas/uso terapéutico , Factores Inmunológicos/uso terapéutico , Inmunosupresores/uso terapéutico , Lactante , Masculino , Persona de Mediana Edad , Miastenia Gravis/inmunología , Miastenia Gravis/patología , Miastenia Gravis/terapia , Bromuro de Piridostigmina/uso terapéutico , Estudios Retrospectivos , Distribución por Sexo , Timectomía , Adulto JovenRESUMEN
Epilepsy is a chronic neurological disorder. Drug-resistant epilepsy (DRE) accounts for about one-third of epilepsy patients worldwide. Peimine, a main active component of Fritillaria, has been reported to show anti-inflammatory effects. However, its potential therapeutic role in DRE is not yet fully understood. In this work, a DRE rat model was established by injecting 1 µg kainic acid (KA), followed by a 250 mg/kg administration of valproic acid (VPA) from day 4-31. Rats were treated with different doses of peimine (2.5 mg/kg, 5 mg/kg and 10 mg/kg) daily from day 32-62. In vitro, BV-2 microglia were exposed to different doses of peimine (7.5 µg/ml, 15 µg/ml, and 30 µg/ml) in presence of LPS. The aim of this study was to investigate the potential therapeutic effects of peimine on DRE. The results showed that peimine efficiently suppressed the KA-induced epileptic behaviors of rats in a dose-dependent manner, as recorded by electroencephalography. Furthermore, peimine ameliorated hippocampal neuron injury in DRE rats, and promoted an M1-to-M2 microglial phenotype shift in a dose-dependent manner. Mechanistically, peimine inhibited the TLR4/NF-κB/HIF-1α signaling pathway both in vivo and in vitro. Additionally, peimine suppressed the apoptosis of primary neurons induced by LPS-treated microglia. In conclusion, peimine augments the microglial polarization towards an M2 phenotype by inhibiting the TLR4/NF-κB/HIF-1α signaling pathway, thereby attenuating DRE.
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Atherosclerosis (AS) is a chronic inflammatory vascular disease, which is the common pathological basis of cardiovascular and cerebrovascular diseases. The immune inflammatory response throughout the course of AS has been evidenced by studies, in which a large number of immune cells and inflammatory factors play a crucial role in the pathogenesis of AS. The inflammation related to AS is mainly mediated by inflammatory cytokines (IL-1ß, IL-6, IL-18, TNF-α, hs-CRP, SAA), inflammatory enzymes (Lp-PLA2, sPLA2-IIA, MMPs), and inflammatory signaling pathways (P38 MAPK signaling pathway, NF-κB signaling pathway, TLR2/4 signaling pathway). It is involved in the pathophysiological process of AS, and the degree of inflammation measured by it can be used to evaluate the risk of progression of AS plaque instability. In recent years, traditional Chinese medicine (TCM) has shown the advantage of minimal side effects in immune regulation and has made some progress in the prevention and treatment of AS. Mesenchymal stem cells (MSCs), as self-renewal, highly differentiated, and pluripotent stem cells with anti-inflammatory properties and immune regulation, have been widely used for AS treatment. They also play an important inflammation-immune regulatory function in AS. Notably, in terms of regulating immune cells and inflammatory factors, compared with TCM and its compound, the combination therapy has obvious anti-inflammatory advantages over the use of MSCs alone. It is an important means to further improve the efficacy of AS and provides a new way for the prevention and treatment of AS.
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Cities play an important role in achieving sustainable development goals (SDGs) to promote economic growth and meet social needs. Especially satellite imagery is a potential data source for studying sustainable urban development. However, a comprehensive dataset in the United States (U.S.) covering multiple cities, multiple years, multiple scales, and multiple indicators for SDG monitoring is lacking. To support the research on SDGs in U.S. cities, we develop a satellite imagery dataset using deep learning models for five SDGs containing 25 sustainable development indicators. The proposed dataset covers the 100 most populated U.S. cities and corresponding Census Block Groups from 2014 to 2023. Specifically, we collect satellite imagery and identify objects with state-of-the-art object detection and semantic segmentation models to observe cities' bird's-eye view. We further gather population, nighttime light, survey, and built environment data to depict SDGs regarding poverty, health, education, inequality, and living environment. We anticipate the dataset to help urban policymakers and researchers to advance SDGs-related studies, especially applying satellite imagery to monitor long-term and multi-scale SDGs in cities.
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The high incidence and disability rates of stroke pose a heavy burden on society. Inflammation is a significant pathological reaction that occurs after an ischemic stroke. Currently, therapeutic methods, except for intravenous thrombolysis and vascular thrombectomy, have limited time windows. Mesenchymal stem cells (MSCs) can migrate, differentiate, and inhibit inflammatory immune responses. Exosomes (Exos), which are secretory vesicles, have the characteristics of the cells from which they are derived, making them attractive targets for research in recent years. MSC-derived exosomes can attenuate the inflammatory response caused by cerebral stroke by modulating damage-associated molecular patterns. In this review, research on the inflammatory response mechanisms associated with Exos therapy after an ischemic injury is discussed to provide a new approach to clinical treatment.
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Purpose: This study aimed to clarify the effect of early glucocorticoid (GC) application on achieving minimal manifestation (MM) status or better in the treatment of myasthenia gravis (MG) in the early clinical phase. Methods: A retrospective analysis was performed using data from 336 patients with MG who received GC therapy from January 2015 to September 2022 in the Zhengzhou University Henan Institute of Medical and Pharmaceutical Sciences Myasthenia Gravis Biobank (ZMB). Patients were divided into two groups: the early mono-GC group (treated with GC within 6 months of MG onset) and the delayed mono-GC group. Results: Kaplan-Meier analysis showed that the early mono-GC group achieved MM status earlier and more frequently than the delayed mono-GC group (log-rank test, p = 0.0082; hazard ratio [HR], 1.66; p = 0.011). The early mono-GC group had a lower maintenance oral GC dose than the delayed mono-GC group. In multivariate Cox regression analysis, early mono-GC (HR, 1.50; p = 0.043), early-onset MG (EOMG) (HR, 1.74; p = 0.034), and ocular MG (OMG) (HR, 1.90; p = 0.007) were associated with MM status or better. In conclusion, early mono-GC, EOMG, and OMG were positive predictors of treatment goals. In EOMG, OMG, and acetylcholine receptor antibody-positive MG (AChR-MG) subgroups, the maintenance oral GC doses in the early mono-GC group were significantly lower than the doses in the delayed mono-GC group (p < 0.05). Conclusion: Early intervention with GC led to better long-term outcomes and reduced the necessary maintenance dose of oral GC for patients with MG. EOMG and OMG were positive predictors of MM status or better with mono-GC.
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HIGHLIGHTS: Metal-organic frameworks (MOFs) are used to directly initiate the gelation of graphene oxide (GO), producing MOF/rGO aerogels. The ultralight magnetic and dielectric aerogels show remarkable microwave absorption performance with ultralow filling contents. The development of a convenient methodology for synthesizing the hierarchically porous aerogels comprising metal-organic frameworks (MOFs) and graphene oxide (GO) building blocks that exhibit an ultralow density and uniformly distributed MOFs on GO sheets is important for various applications. Herein, we report a facile route for synthesizing MOF/reduced GO (rGO) aerogels based on the gelation of GO, which is directly initiated using MOF crystals. Free metal ions exposed on the surface of MIL-88A nanorods act as linkers that bind GO nanosheets to a three-dimensional porous network via metal-oxygen covalent or electrostatic interactions. The MOF/rGO-derived magnetic and dielectric aerogels Fe3O4@C/rGO and Ni-doped Fe3O4@C/rGO show notable microwave absorption (MA) performance, simultaneously achieving strong absorption and broad bandwidth at low thickness of 2.5 (- 58.1 dB and 6.48 GHz) and 2.8 mm (- 46.2 dB and 7.92 GHz) with ultralow filling contents of 0.7 and 0.6 wt%, respectively. The microwave attenuation ability of the prepared aerogels is further confirmed via a radar cross-sectional simulation, which is attributed to the synergistic effects of their hierarchically porous structures and heterointerface engineering. This work provides an effective pathway for fabricating hierarchically porous MOF/rGO hybrid aerogels and offers magnetic and dielectric aerogels for ultralight MA.
RESUMEN
Myasthenia gravis (MG) is characterized by autoimmune damage to the postsynaptic membrane of the neuromuscular junction (NMJ) with impaired postsynaptic acetylcholine receptor (AChR) aggregation. Low-density lipoprotein receptor-related protein 4 (LRP4) plays an important role in AChR aggregation at endplate membranes via the Agrin-LRP4-muscle-specific receptor tyrosine kinase (MuSK) cascade. Sorting nexin 17 (SNX17) regulates the degradation and recycling of various internalized membrane proteins. However, whether SNX17 regulates LRP4 remains unclear. Therefore, we examined the regulatory effects of SNX17 on LRP4 and its influence on AChR aggregation in MG. We selected C2C12 myotubes and induced LRP4 internalization via stimulation with anti-LRP4 antibody and confirmed intracellular interaction between SNX17 and LRP4. SNX17 knockdown and overexpression confirmed that SNX17 promoted MuSK phosphorylation and AChR aggregation by increasing cell surface LRP4 expression. By establishing experimental autoimmune MG (EAMG) mouse models, we identified that SNX17 upregulation improved fragmentation of the AChR structure at the NMJ and alleviated leg weakness in EAMG mice. Thus, these results reveal that SNX17 may be a novel target for future MG therapy.
Asunto(s)
Miastenia Gravis Autoinmune Experimental , Receptores Colinérgicos , Animales , Ratones , Acetilcolina , Proteínas Relacionadas con Receptor de LDL , Lipoproteínas LDL , Proteínas Tirosina Quinasas Receptoras , Nexinas de Clasificación/genéticaRESUMEN
PURPOSE: The purpose of this monocentric retrospective observational study is to investigate whether a loading dose of ticagrelor treatment before percutaneous coronary intervention (PCI) procedure improves the early reperfusion and short-term heart function in East-Asian ST segment elevation myocardial infarction (STEMI) patients. PATIENTS AND METHODS: The study included 326 STEMI patients undergoing primary PCI in Jiading Central Hospital. One hundred and forty patients received a loading dose of ticagrelor before entering the catheter laboratory. One hundred and eighty-six patients received a loading dose of ticagrelor in the catheter laboratory before the initiation of PCI. Reperfusion endpoints included the presence of self-patency in the culprit artery, the ST-segment elevation resolution over 50% within 24 h after PCI, and the presence of no-reflow in the culprit artery. Clinical endpoints included all-cause mortality, new-onset heart failure, reinfarction and stent thrombosis within 28 days after PCI. Secondary clinical endpoints included mechanical complications and bleeding events. RESULTS: In comparison with the in-lab treatment group, the preprocedural treatment group had a significant higher proportion of self-patency in the culprit artery (25.71% vs 16.67%, P=0.045) and early ST-segment elevation resolution (48.57% vs 27.96%, P<0.001). Preprocedural ticagrelor treatment was associated with a significant reduction of new-onset heart failure (9.29% vs 18.82%, p=0.016). Stent thrombosis risks were numerically reduced in the preprocedural treatment group (0.71% vs 1.61%, P=0.466). The rates of major cardiovascular adverse events, reinfarctions and mortality did not differ between the two groups. Bleeding events in the preprocedural treatment group was notn significantly higher than the in-lab treatment group (4.39% vs 1.39%, P=0.142). CONCLUSION: Preprocedural administration of a loading dose of ticagrelor was associated with improved early reperfusion and reduced short-term heart failure in East-Asian STEMI patients undergoing primary PCI, but care should be taken for excess bleeding events.