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INTRODUCTION: No studies explored the long-term outcomes of neural cell adhesion molecule 1 (NCAM1) associated membranous lupus nephritis (MLN) patients. METHOD: We performed immunohistochemical studies on kidney biopsy specimens against NCAM1 in consecutive MLN patients. The clinical and histopathological characteristics and outcomes of cases of NCAM1 associated MLN patients are described and compared with NCAM1 negative patients. In addition, we detected serum circulating anti-NCAM1 antibodies through western blotting and indirect immunofluorescence assays. RESULTS: Among 361 MLN cases, 18 (5.0%) were glomerular NCAM1-positive. NCAM1 positive MLN patients were older [35 years (IQR 27-43) versus 28 (22-37); P = 0.050) and had lower systemic lupus erythematosus disease activity index [11 (IQR 8-12) versus 14 (10-18); P = 0.007], serum creatinine [60 µmol/L (IQR 50-70) versus 70 (54-114); P = 0.029], activity index [3 (IQR 2-6) versus 6 (3-9); P = 0.045] at kidney biopsy compared with NCAM1 negative patients. The percentage of positive anti-Sjogren's syndrome related antigen A antibodies in NCAM1 positive patients was significantly greater (83.3% versus 58.2%; P = 0.035) than in the NCAM1 negative patients. However, no evidence of neuropsychiatric disorders was found in these 18 patients. There were no significant differences in the treatment response and the risk of end stage renal diseases between NCAM1 positive and negative groups (P = 0.668 and P = 0.318, respectively). But the risk of death was much higher in the NCAM1 positive group than the NCAM1 negative group (27.8% vs. 8.1%, P = 0.007). Moreover, the risk of death was also much higher in the NCAM1 positive group than the matched NCAM1 negative group (Log-rank P = 0.013). Additionally, circulating anti-NCAM1 antibodies can be detected in 1/5 (20%) patients who had serum available. CONCLUSION: The prevalence of NCAM1 positivity was 5.0% in our cohort of MLN and the high mortality in these subgroup patients are needed to validate in future studies.
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Objective: To explore the effect of Gouqi Nuzhen Liuhe Decoction (GNLHD) on the PI3K/mTOR Signaling Pathway for Premature Ovarian Insufficiency (POI) based on system pharmacology. Methods: First, the system pharmacology approach was used to predict the mechanism of GNLHD. Then, mice were randomly divided into model group, positive group, GNLHD high-dose group, GNLHD medium-dose group, and GNLHD low-dose group. Hematoxylin-eosin (HE) staining was used to observe the pathological changes of ovarian tissue under light microscope. The expression levels of estradiol (E2), follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were detected by enzyme-linked immunosorbent assay. The expressions of PI3K, AKT1 and mTOR proteins in ovarian tissue were detected by immunohistochemistry. Results: The results of system pharmacology showed that GNLHD may regulate biological processes and signaling pathways such as: reproductive structure development, reproductive system development, Oocyte meiosis and so on. Compared with the model group, the levels of E2 in the GNLHD group were increased, and the levels of FSH and LH were decreased (P < 0.05). Compared with the model group, the number of mature follicles in the GNLHD group was significantly increased, the number of atretic follicles was relatively decreased, and the expressions of PI3K, AKT1, and MTOR proteins in the GNLHD group were significantly increased (P < 0.05). Conclusion: GNLHD may improve the ovarian function of POI mice by affecting the expression of PI3K, AKT1 and mTOR proteins, promote the growth and development of follicles, increase the E2 level, reduce FSH and LH level, and maintain the stability of the ovarian internal environment.
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OBJECTIVE: This study aims to assess the effectiveness and safety of mesenchymal stem cell (MSC) transplantation in the treatment of inflammatory arthritis. METHODS: Two researchers conducted a comprehensive search of Chinese and English databases from their inception until July 2023. The literature screening and data extraction were then performed. Statistical analysis was carried out using RevMan 5.4 software. RESULTS: A total of 36 relevant RCTs, involving 2,076 participants, were ultimately included in this study. These RCTs encompassed four types of inflammatory arthritis, namely rheumatoid arthritis (RA), osteoarthritis (OA), ankylosing spondylitis (AS), and systemic sclerosis (SSc). The results demonstrated that MSC therapy exhibited improvements in the Visual Analog Scale (VAS) for pain in OA patients (bone marrow: SMD=-0.95, 95 % CI: -1.55 to -0.36, P = 0.002; umbilical cord: SMD=-2.03, 95 % CI: -2.99 to -1.07, P < 0.0001; adipose tissue: SMD=-1.26, 95 % CI: -1.99 to -0.52, P = 0.0009). Specifically, MSCs sourced from adipose tissue showed enhancements in Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain (P = 0.0001), WOMAC physical function (P = 0.001), and total WOMAC scores (P = 0.0003). As for MSC therapy in RA, AS, and SSc, the current systematic review suggests a potential therapeutic effect of MSCs on these inflammatory arthritic conditions. Safety assessments indicated that MSC therapy did not increase the incidence of adverse events. CONCLUSION: MSCs have the potential to alleviate joint pain and improve joint function in patients with inflammatory arthritis. Moreover, MSC therapy appears to be relatively safe and could be considered as a viable alternative treatment option for inflammatory arthritis.
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There is growing interest in the contribution of ultrafine particles to air quality, climate, and human health. Ultrafine particles are of central significance for the influence of radiative forcing of climate change by involving in the formation of clouds and precipitation. Moreover, exposure to ultrafine particles can enhance the disease burden. The determination of those effects of ultrafine particles strongly depends on their chemical composition and physicochemical properties. This review focuses on the advanced techniques for the characterization of chemical composition and physicochemical properties of ultrafine particles in the past five years. The current analytical methodologies are broadly classified into electron and X-ray microscopy, optical spectroscopy and microscopy, electrical mobility, and mass spectrometry, and then described and discussed its operation principle, advantages, and limitations. Besides measurements, application of the state-of-the-art techniques is briefly reviewed to help us to promote a better understanding of atmospheric ultrafine particles relevant to air quality, climate, and health.
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Compared to pathogens Pseudomonas aeruginosa and P. putida, P. donghuensis HYS has stronger virulence towards Caenorhabditis elegans. However, the underlying mechanisms haven't been fully understood. The heme synthesis system is essential for Pseudomonas virulence, and former studies of HemN have focused on the synthesis of heme, while the relationship between HemN and Pseudomonas virulence were barely pursued. In this study, we hypothesized that hemN2 deficiency affected 7-hydroxytropolone (7-HT) biosynthesis and redox levels, thereby reducing bacterial virulence. There are four hemN genes in P. donghuensis HYS, and we reported for the first time that deletion of hemN2 significantly reduced the virulence of HYS towards C. elegans, whereas the reduction in virulence by the other three genes was not significant. Interestingly, hemN2 deletion significantly reduced colonization of P. donghuensis HYS in the gut of C. elegans. Further studies showed that HemN2 was regulated by GacS and participated in the virulence of P. donghuensis HYS towards C. elegans by mediating the synthesis of the virulence factor 7-HT. In addition, HemN2 and GacS regulated the virulence of P. donghuensis HYS by affecting antioxidant capacity and nitrative stress. In short, the findings that HemN2 was regulated by the Gac system and that it was involved in bacterial virulence via regulating 7-HT synthesis and redox levels were reported for the first time. These insights may enlighten further understanding of HemN-based virulence in the genus Pseudomonas.
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BACKGROUND: Osteoarthritis (OA) is a debilitating joint disorder characterized by the progressive degeneration of articular cartilage. Although the role of ion channels in OA pathogenesis is increasingly recognized, diagnostic markers and targeted therapies remain limited. METHODS: In this study, we analyzed the GSE48556 dataset to identify differentially expressed ion channel-related genes (DEGs) in OA and normal controls. We employed machine learning algorithms, least absolute shrinkage and selection operator(LASSO), and support vector machine recursive feature elimination(SVM-RFE) to select potential diagnostic markers. Then the gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) were performed to explore the potential diagnostic markers' involvement in biological pathways. Finally, weighted gene co-expression network analysis (WGCNA) was used to identify key genes associated with OA. RESULTS: We identified a total of 47 DEGs, with the majority involved in transient receptor potential (TRP) pathways. Seven genes (CHRNA4, GABRE, HTR3B, KCNG2, KCNJ2, LRRC8C, and TRPM5) were identified as the best characteristic genes for distinguishing OA from healthy samples. We performed clustering analysis and identified two distinct subtypes of OA, C1, and C2, with differential gene expression and immune cell infiltration profiles. Then we identified three key genes (PPP1R3D, ZNF101, and LOC651309) associated with OA. We constructed a prediction model using these genes and validated it using the GSE46750 dataset, demonstrating reasonable accuracy and specificity. CONCLUSIONS: Our findings provide novel insights into the role of ion channel-related genes in OA pathogenesis and offer potential diagnostic markers and therapeutic targets for the treatment of OA.
As society ages, the incidence of knee osteoarthritis continues to rise, bringing with it a series of social impacts and medical pressure. Despite the increasing recognition of the role of ion channels in the pathogenesis of OA, diagnostic markers and targeted therapies remain limited.This study investigated the role of TRP as possible diagnostic tools for OA.Seven TRP-related genes were identified as the best traits to distinguish OA from healthy samples, and then we constructed and validated risk scores for three key genes (PPP1R3D, ZNF101, and LOC651309) relevant to OA ion channel gene modules.Our findings provide novel insights into the role of ion channel-related genes in OA pathogenesis and offer a reference for further clinical diagnosis.
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Biomarcadores , Biología Computacional , Canales Iónicos , Aprendizaje Automático , Osteoartritis , Humanos , Osteoartritis/genética , Osteoartritis/diagnóstico , Canales Iónicos/genética , Biología Computacional/métodos , Biomarcadores/metabolismo , Perfilación de la Expresión Génica , Redes Reguladoras de Genes , Máquina de Vectores de SoporteRESUMEN
OBJECTIVE: To explore the material basis of the difference of efficacy of Dahuang (Radix Et Rhizoma Rhei Palmati)-Taoren (Semen Persicae) (DT) drugs with different proportions. METHODS: Samples of different ratios of Dahuang (Radix et Rhizoma Rhei Palnati, DH) to Taoren (Semen Persicae, TR) (Group A 1:1, B 2:3, C 3:2) were analyzed based on gas chromatography time-of-flight mass spectrometry untargeted metabolomics technique. RESULTS: A total of 240 primary metabolites were detected. Forty-one differential metabolites involved nine differential metabolic pathways, of which four were closely related to the efficacy of DT in the treatment of heat and blood stasis syndrome. These pathways included the biosynthesis of amino acid (phenylalanine tyrosine and tryptophan), flavonoids, unsaturated fatty acids, and the glycolysis/glycogenesis pathway. CONCLUSION: There are significant differences in the efficacy of different ratios of DT drugs, and their optimal ratio for the treatment of heat and blood stasis syndrome should be 1:1.
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Medicamentos Herbarios Chinos , Metabolómica , Humanos , Masculino , Cromatografía de Gases y Espectrometría de Masas , AnimalesRESUMEN
BACKGROUND: Previous randomized controlled trials (RCTs) suggested that gut microbiota-based therapies may be effective in treating autoimmune diseases, but a systematic summary is lacking. METHODS: Pubmed, EMbase, Sinomed, and other databases were searched for RCTs related to the treatment of autoimmune diseases with probiotics from inception to June 2022. RevMan 5.4 software was used for meta-analysis after 2 investigators independently screened literature, extracted data, and assessed the risk of bias of included studies. RESULTS: A total of 80 RCTs and 14 types of autoimmune disease [celiac sprue, SLE, and lupus nephritis (LN), RA, juvenile idiopathic arthritis (JIA), spondyloarthritis, psoriasis, fibromyalgia syndrome, MS, systemic sclerosis, type 1 diabetes mellitus (T1DM), oral lichen planus (OLP), Crohn's disease, ulcerative colitis] were included. The results showed that gut microbiota-based therapies may improve the symptoms and/or inflammatory factor of celiac sprue, SLE and LN, JIA, psoriasis, PSS, MS, systemic sclerosis, Crohn's disease, and ulcerative colitis. However, gut microbiota-based therapies may not improve the symptoms and/or inflammatory factor of spondyloarthritis and RA. Gut microbiota-based therapies may relieve the pain of fibromyalgia syndrome, but the effect on fibromyalgia impact questionnaire score is not significant. Gut microbiota-based therapies may improve HbA1c in T1DM, but its effect on total insulin requirement does not seem to be significant. These RCTs showed that probiotics did not increase the incidence of adverse events. CONCLUSIONS: Gut microbiota-based therapies may improve several autoimmune diseases (celiac sprue, SLE and LN, JIA, psoriasis, fibromyalgia syndrome, PSS, MS, T1DM, Crohn's disease, and ulcerative colitis).
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Enfermedades Autoinmunes , Microbioma Gastrointestinal , Ensayos Clínicos Controlados Aleatorios como Asunto , Enfermedades Reumáticas , Humanos , Enfermedades Autoinmunes/terapia , Enfermedades Reumáticas/terapia , Probióticos/uso terapéutico , Probióticos/administración & dosificación , Resultado del TratamientoRESUMEN
Extensive research has focused on the impact of weather on working capacity and income. However, in regions where income data largely relies on surveys, a pivotal yet underexplored question is whether weather not only influence real income but also introduce biases into survey-collected income data. We analyze longitudinal data from the China Health and Nutrition Survey and corresponding weather records from the Global Surface Summary of the Day, and uncover a negative correlation between survey-day temperature and self-reported annual income from the previous year. With a series of robustness checks, we confirm that the effect is primarily driven by behavioral factors rather than actual income changes. And threshold regression analyses show that the impact of temperature is more pronounced on hot days and relatively subdued or even reversed on cooler days. Further analyses indicate that mood, rather than cognitive capacity, plays a central role in causing the observed downward bias.
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The mesenchymal subtype of glioblastoma (GBM) cells characterized by aggressive invasion and therapeutic resistance is thought to be dependent on cell-intrinsic alteration and extrinsic cellular crosstalk. Tumor-associated macrophages (TAMs) are pivotal in tumor progression, chemo-resistance, angiogenesis, and stemness maintenance. However, the impact of TAMs on the shifts in glioma stem cells (GSCs) states remains largely uncovered. Herein, we showed that the triggering receptor expressed on myeloid cells-1 (TREM1) preferentially expressed by M2-like TAMs and induced GSCs into mesenchymal-like states by modulating the secretion of TGFß2, which activated the TGFßR/SMAD2/3 signaling in GSCs. Furthermore, we demonstrated that TREM1 was transcriptionally regulated by HIF1a under the hypoxic environment and thus promoted an immunosuppressive type of TAMs via activating the TLR2/AKT/mTOR/c-MYC axis. Collectively, this study reveals that cellular communication between TAMs and GSCs through the TREM1-mediated TGFß2/TGFßR axis is involved in the mesenchymal-like transitions of GSCs. Our study provides valuable insights into the regulatory mechanisms between the tumor immune microenvironment and the malignant characteristics of GBM, which can lead to potential novel strategies targeting TAMs for tumor control.
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Células Madre Neoplásicas , Receptor Activador Expresado en Células Mieloides 1 , Microambiente Tumoral , Macrófagos Asociados a Tumores , Humanos , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Células Madre Neoplásicas/inmunología , Receptor Activador Expresado en Células Mieloides 1/metabolismo , Receptor Activador Expresado en Células Mieloides 1/genética , Macrófagos Asociados a Tumores/metabolismo , Macrófagos Asociados a Tumores/inmunología , Animales , Línea Celular Tumoral , Transducción de Señal , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/inmunología , Glioma/patología , Glioma/genética , Glioma/metabolismo , Glioma/inmunología , Ratones , Glioblastoma/patología , Glioblastoma/genética , Glioblastoma/metabolismo , Glioblastoma/inmunología , Factor de Crecimiento Transformador beta2/metabolismo , Factor de Crecimiento Transformador beta2/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Regulación Neoplásica de la Expresión Génica , Proteína Smad2/metabolismo , Proteína Smad2/genéticaRESUMEN
Ferroptosis, a distinct form of cell death, is characterized by the iron-mediated oxidation of lipids and is finely controlled by multiple cellular metabolic pathways. These pathways encompass redox balance, iron regulation, mitochondrial function, as well as amino acid, lipid, and sugar metabolism. Additionally, various disease-related signaling pathways also play a role in the regulation of ferroptosis. In recent years, with the introduction of the concept of ferroptosis and the deepening of research on its mechanism, ferroptosis is closely related to various biological conditions of eye diseases, including eye organ development, aging, immunity, and cancer. This article reviews the development of the concept of ferroptosis, the mechanism of ferroptosis, and its latest research progress in ophthalmic diseases and reviews the research on ferroptosis in ocular diseases within the framework of metabolism, active oxygen biology, and iron biology. Key regulators and mechanisms of ferroptosis in ocular diseases introduce important concepts and major open questions in the field of ferroptosis and related natural compounds. It is hoped that in future research, further breakthroughs will be made in the regulation mechanism of ferroptosis and the use of ferroptosis to promote the treatment of eye diseases. At the same time, natural compounds may be the direction of new drug development for the potential treatment of ferroptosis in the future. Open up a new way for clinical ophthalmologists to research and prevent diseases.
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Oftalmopatías , Ferroptosis , Humanos , Oftalmopatías/tratamiento farmacológico , Ojo , HierroRESUMEN
Coping capacity is a key aspect of driver-vehicle interaction when drivers observe and make decisions, and is of great importance for drivers. However, different drivers have different self-cognition and assess their driving abilities differently, especially for novice drivers. Based on questionnaire data, this study has investigated the coping capacities of drivers in both static environments and dynamic environments. With the ANOVA analysis method and the structural equation model (SEM), this study has verified the effects of gender and driving factors (driving years, driving frequency, driving time) on drivers' coping capacities based on drivers' self-assessment scores and mutual assessment scores. Drivers' self-assessment scores show significant effects of all factors on drivers' coping capacities, and drivers' mutual assessment scores show significant effects of all factors, excluding driving time, on drivers' coping capacities. Also, it has been found that all drivers in the driving year group have cognitive biases. It seems that first-year drivers are always overconfident with their driving skills, while drivers with a driving experience of more than three years usually score driving skills of themselves and other drivers most conservatively. With increased exposure to various traffic conditions, experienced drivers are more aware of their limitations in dealing with complex traffic situations, while novice drivers do not know their lack of capability to properly respond to any unexpected situation they could encounter.
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Accidentes de Tránsito , Conducción de Automóvil , Cognición , Encuestas y Cuestionarios , Sesgo , Adaptación PsicológicaRESUMEN
Selecting an appropriate intensity of epidemic prevention and control measures is of vital significance to promoting the two-way dynamic coordination of epidemic prevention and control and economic development. In order to balance epidemic control and economic development and suggest scientific and reasonable traffic control measures, this paper proposes a SEIQR model considering population migration and the propagation characteristics of the exposed and the asymptomatic, based on the data of COVID-19 cases, Baidu Migration, and the tourist economy. Further, the factor traffic control intensity is included in the model. After determining the functional relationship between the control intensity and the number of tourists and the cumulative number of confirmed cases, the NSGA-II algorithm is employed to perform multi-objective optimization with consideration of the requirements for epidemic prevention and control and for economic development to get an appropriate traffic control intensity and suggest scientific traffic control measures. With Xi'an City as an example. The results show that the Pearson correlation coefficient between the predicted data of this improved model and the actual data is 0.996, the R-square in the regression analysis is 0.993, with a significance level of below 0.001, suggesting that the predicted data of the model are more accurate. With the continuous rise of traffic control intensity in different simulation scenarios, the cumulative number of cases decreases by a significant amplitude. While balancing the requirements for epidemic prevention and control and for tourist economy development, the model works out the control intensity to be 0.68, under which some traffic control measures are suggested. The model presented in this paper can be used to analyze the impacts of different traffic control intensities on epidemic transmission. The research results in this paper reveal the traffic control measures balancing the requirements for epidemic prevention and control and for economic development.
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COVID-19 , Epidemias , Humanos , COVID-19/epidemiología , COVID-19/prevención & control , Ciudades/epidemiología , Desarrollo Económico , China/epidemiologíaRESUMEN
To explore the molecular network mechanism of Celastrol in the treatment of rheumatoid arthritis (RA) based on a novel strategy (integrated systems pharmacology, proteomics, transcriptomics and single-cell transcriptomics). Firstly, the potential targets of Celastrol and RA genes were predicted through the database, and the Celastrol-RA targets were obtained by taking the intersection. Then, transcriptomic data and proteomic data of Celastrol treatment of RA were collected. Subsequently, Celastrol-RA targets, differentially expressed genes, and differentially expressed proteins were imported into Metascape for enrichment analysis, and related networks were constructed. Finally, the core targets of Celastrol-RA targets, differentially expressed genes, and differentially expressed proteins were mapped to synoviocytes of RA mice to find potential cell populations for Celastrol therapy. A total of 195 Celastrol-RA targets, 2068 differential genes, 294 differential proteins were obtained. The results of enrichment analysis showed that these targets, genes and proteins were mainly related to extracellular matrix organization, TGF-ß signaling pathway, etc. The results of single cell sequencing showed that the main clusters of these targets, genes, and proteins could be mapped to RA synovial cells. For example, Mmp9 was mainly distributed in Hematopoietic cells, especially in Ptprn+fibroblast. The results of molecular docking also suggested that Celastrol could stably combine with molecules predicted by network pharmacology. In conclusion, this study used systems pharmacology, transcriptomics, proteomics, single-cell transcriptomics to reveal that Celastrol may regulate the PI3K/AKT signaling pathway by regulating key targets such as TNF and IL6, and then play an immune regulatory role.
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Artritis Reumatoide , Triterpenos Pentacíclicos , Triterpenos , Ratones , Animales , Farmacología en Red , Triterpenos/farmacología , Triterpenos/uso terapéutico , Simulación del Acoplamiento Molecular , Multiómica , Proteómica , Fosfatidilinositol 3-Quinasas , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/genéticaRESUMEN
Alkyl-PAHs (APAHs) have been identified worldwide, which could rapidly react with chlorine and OH radicals in the atmosphere. In this study, a comprehensive investigation is conducted for SOA generated by a representative alkyl-naphthalene (1-methyl naphthalene, 1-MN) initiated by Cl, including yield, chemical composition, and volatility of SOA. To better understand 1-MN atmospheric oxidation, reaction mechanisms of 1MN with Cl atoms and OH radicals are proposed and compared under different nitrogen oxides (NOx) conditions. The SOA yields are comparable for Cl-initiated and OH-initiated reactions under high NOx conditions but increased in Cl-initiated reactions under low NOx conditions. The compounds with ten carbons are more abundant in Cl-initiated SOA, while compounds with nine carbons have higher intensity, suggesting that Cl caused ring-retained and alkyl-lost products and OH produces ring-broken and alkyl-retained compounds. The volatility of SOA is remarkably low, and SOA formed from Cl oxidation is slightly higher than that from OH oxidation. These results reveal that 1MN-derived SOA with OH and Cl radicals would have different physical-chemical properties and may play an important role in air quality and health effects.
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OBJECTIVE: Endobutton technique could provide flexible coracoclavicular (CC) stabilization for acromioclavicular joint (ACJ) dislocation and achieved good clinical outcomes. However, the difficult part of this technique was placement of the Endobutton to the coracoid base. In this study, we designed an Endobutton installation device to place the Endobutton at the coracoid base. And we examined the clinical and radiographic outcomes of patients with acute Rockwood type III ACJ dislocation repaired with Endobutton using this device. METHODS: We designed an Endobutton installation device to place the Endobutton at the coracoid base to achieve CC stabilization. We retrospectively reviewed 42 patients with acute Rockwood type III ACJ dislocation who underwent CC stabilization with Endobuttons placed either using this novel device (group I, n = 19) or the traditional technique (CC stabilization without using special device, group II, n = 23) from January 2015 to April 2020. The two groups were compared regarding the operative time, intraoperative blood loss, and clinical and radiologic outcomes at final follow-up. The operation-related complications were also evaluated. The Student's t test and the Mann-Whitney U-test were used to compare differences in continuous variables. Differences in categorical variables were assessed with either the Pearson's chi-squared test or Fisher's exact test. RESULTS: Forty-two patients were clinically followed up for a minimum of 12 months. Compared with group II, group I had a significantly shorter mean operative time (56.05 ± 7.82 min vs. 65.87 ± 7.43 min, p < 0.01) and significantly lesser mean intraoperative blood loss (67.89 ± 14.75 mL vs. 94.78 ± 25.01 mL, p < 0.01). At final follow-up, there were no significant differences between the two groups in the visual analog scale score for pain, Oxford Shoulder Score, Disabilities of the Arm, Shoulder, and Hand score, and postoperative CC distance of the affected side. Loss of reduction occurred in four patients in group I and three patients in group II (p = 0.68); there were no other operation-related complications in either group. CONCLUSIONS: The Endobutton installation device makes placement of the Endobutton at the coracoid base easier and achieves satisfactory clinical and radiologic outcomes without additional complications in acute Rockwood type III ACJ dislocation.
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Articulación Acromioclavicular , Luxaciones Articulares , Luxación del Hombro , Humanos , Luxaciones Articulares/cirugía , Estudios Retrospectivos , Articulación Acromioclavicular/cirugía , Pérdida de Sangre Quirúrgica , Resultado del Tratamiento , Luxación del Hombro/cirugíaRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Shou Tai Wan (STW), a traditional Chinese medicine formula, has been historically used for the treatment of recurrent spontaneous abortion (RSA). Despite its long-standing usage, the exact mechanism underlying the therapeutic effects of STW remains unclear in the existing literature. AIMS OF THIS STUDY: To explore the Pharmacological Mechanism of STW on RSA. METHODS: A network pharmacological methodology was utilized to predict the active compounds and potential targets of STW, collect the RSA targets and other human proteins of STW, and analyze the STW related networks. The animal experiments were also performed to validate the effect of STW on RSA. RESULTS: The results of network analysis showed that STW may regulate PI3K/AKT, MAPK, FoxO signaling pathways and so on. Animal experiment established the RSA model with CBA/J × DBA/2 mice. It was found that STW can reduce the embryo absorption rate of RSA group (p < 0.05) and balance the expression of Th 1/Th2 type cytokines compared with the model group. After 14 days of administration, the decidual and placental tissues were taken and the CD4+ T cells were isolated, and the phosphorylation level of signaling pathway was detected by Springbio720 antibody microarray. This experiment found that STW can significantly up-regulate the phosphorylation levels of STAT3 and STAT6 proteins in the STAT signaling pathway, and down-regulating the phosphorylation level of STAT1 protein. STW also significantly up-regulated the phosphorylation levels of Raf1, A-Raf, Ask1, Mek1, Mek2, JKK1, ERK1, ERK2, c-fos, c-Jun and CREB proteins in the MAPK signaling pathway, and down-regulate the phosphorylation levels of MEK6 and IKKb proteins. Compared with the RSA group, the STW group increased the expression levels of ERK1/2 mRNA and proteins and p-ERK1/2 proteins, and there was a statistical difference (p < 0.05). This is consistent with the chip results. CONCLUSION: STW may achieve therapeutic effects by interfering with the signaling pathways, biological processes and targets discovered in this study. It provides a new perspective for revealing the immunological mechanism of STW in the treatment of RSA, and also provides a theoretical basis for the clinical use of STW in the treatment of RSA.
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Aborto Habitual , Fosfatidilinositol 3-Quinasas , Ratones , Animales , Embarazo , Femenino , Humanos , Placenta , Ratones Endogámicos DBA , Ratones Endogámicos CBA , Aborto Habitual/tratamiento farmacológicoRESUMEN
Breast cancer is the most prevalent cancer worldwide and its incidence increases with age, posing a significant threat to women's health globally. Due to the clinical heterogeneity of breast cancer, the majority of patients develop drug resistance and metastasis following treatment. Ferroptosis, a form of programmed cell death dependent on iron, is characterized by the accumulation of lipid peroxides, elevated levels of iron ions and lipid peroxidation. The underlying mechanisms and signalling pathways associated with ferroptosis are intricate and interconnected, involving various proteins and enzymes such as the cystine/glutamate antiporter, glutathione peroxidase 4, ferroptosis inhibitor 1 and dihydroorotate dehydrogenase. Consequently, emerging research suggests that ferroptosis may offer a novel target for breast cancer treatment; however, the mechanisms of ferroptosis in breast cancer urgently require resolution. Additionally, certain natural compounds have been reported to induce ferroptosis, thereby interfering with breast cancer. Therefore, this review not only discusses the molecular mechanisms of multiple signalling pathways that mediate ferroptosis in breast cancer (including metastasis, invasion and proliferation) but also elaborates on the mechanisms by which natural compounds induce ferroptosis in breast cancer. Furthermore, this review summarizes potential compound types that may serve as ferroptosis inducers in future tumour cells, providing lead compounds for the development of ferroptosis-inducing agents. Last, this review proposes the potential synergy of combining natural compounds with traditional breast cancer drugs in the treatment of breast cancer, thereby suggesting future directions and offering new insights.
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Neoplasias de la Mama , Ferroptosis , Humanos , Femenino , Apoptosis , Ácido Glutámico , Hierro , Peroxidación de LípidoRESUMEN
Oxidored-nitro domain-containing protein 1 (NOR1) is a critical tumour suppressor gene, though its regulatory mechanism in oxidative stress of glioblastoma (GBM) remains unclear. Hence, further study is needed to unravel the function of NOR1 in the progression of oxidative stress in GBM. In this study, we evaluated the expression of NOR1 and nuclear respiratory factor 1 (NRF1) in GBM tissue and normal brain tissue (NBT) using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot (WB), and investigated their relationship. We then induced oxidative stress in U251 cells through H2O2 treatment and conducted Cell Count-ing Kit-8, Transwell and wound healing assays to analyse cell proliferation, invasion and migration. Cell apoptosis was assessed by flow cytometry and TUNEL staining. We also measured the activities of superoxide dismutase and catalase, as well as the level of reactive oxygen species (ROS) using biochemical techniques. Via qRT-PCR and WB, the mRNA and protein expression levels of NOR1 and NRF1 were determined. Chromatin immunoprecipitation (ChIP) assays were applied to validate NRF1's interaction with NOR1. Our results showed that the expression of NOR1 and NRF1 was low in GBM, and their expression levels were positively correlated. H2O2-induced oxidative stress reduced NRF1 and NOR1 expression levels and increased the ROS level. The ChIP assay confirmed the binding of NRF1 to NOR1. Over-expression of NRF1 attenuated the inhibitory effect of oxidative stress on the proliferation, migration and invasion of U251 cells, which was reversed by knockdown of NOR1.
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Glioblastoma , Factor Nuclear 1 de Respiración , Humanos , Proliferación Celular , Glioblastoma/genética , Peróxido de Hidrógeno/farmacología , Factor Nuclear 1 de Respiración/genética , Estrés Oxidativo , Especies Reactivas de OxígenoRESUMEN
Autoimmune diseases are affected by complex pathophysiology involving multiple cell types, cytokines, antibodies and mimicking factors. Different drugs are used to improve these autoimmune responses, including nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, antibodies, and small molecule drugs (DMARDs), which are prevalent clinically in the treatment of rheumatoid arthritis (RA), etc. However, low cost-effectiveness, reduced efficacy, adverse effects, and patient non-response are unattractive factors driving the development of new drugs such as iguratimod. As a new disease-modifying antirheumatic drug, iguratimod has pharmacological activities such as regulating autoimmune disorders, inflammatory cytokines, regulating immune cell activation, differentiation and proliferation, improving bone metabolism, and inhibiting fibrosis. In recent years, clinical studies have found that iguratimod is effective in the treatment of RA, SLE, IGG4-RD, Sjogren 's syndrome, ankylosing spondylitis, interstitial lung disease, and other autoimmune diseases and rheumatic diseases. The amount of basic and clinical research on other autoimmune diseases is also increasing. Therefore, this review systematically reviews the latest relevant literature in recent years, reviews the research results in recent years, and summarizes the research progress of iguratimod in the treatment of related diseases. This review highlights the role of iguratimod in the protection of autoimmune and rheumatic bone and related immune diseases. It is believed that iguratimod's unique mode of action and its favorable patient response compared to other DMARDs make it a suitable antirheumatic and bone protective agent in the future.