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OBJECTIVES: Emerging evidence indicate that long noncoding RNAs (lncRNAs) may play an important role in the pathogenesis of systemic lupus erythematosus (SLE) however, the contribution of lncRNAs to SLE remains largely unclear. Our study aimed to explore the lncRNA expression profiles in peripheral blood mononuclear cells (PBMCs) from SLE patients. METHODS: LncRNA sequencing was used to detect differentially expressed genes in PBMCs from 5 SLE-MIX samples and 3 healthy controls (HC)-MIX samples, and the expression of selected lncRNAs was further verified by real-time quantitative polymerase chain reaction (RTâqPCR). The correlation of lncRNA expression with laboratory indicators as well the SLE disease activity index 2000 (SLEDAIâ2K) score from 72 SLE patients was assessed by Spearman's test. The association between lncRNA ENST00000597482 and organ involvement in SLE patients was determined by the MannâWhitney U test. Moreover, lymphocyte subsets in peripheral blood from SLE patients were measured by flow cytometry. In addition, the diagnostic value of lncRNAs in predicting SLE was evaluated by receiver operating characteristic (ROC) curve analysis. RESULTS: The lncRNA expression profiles demonstrated 218 differentially expressed lncRNAs, including 121 upregulated genes and 97 downregulated genes, in PBMCs from SLE patients compared to HCs. Among the 10 candidate genes selected, only lncRNA ENST00000597482, which was lower in SLE PBMCs than in HCs, was consistent with the sequencing results. LncRNA ENST00000597482 expression was negatively correlated with SLEDAI-2K score and the titres of ANA antibodies and anti-double-stranded DNA (anti-dsDNA) antibodies. Of note, SLE patients with lower expression of lncRNA ENST00000597482 were prone to develop organ involvement. Furthermore, lncRNA ENST00000597482 exhibited potential diagnostic value in differentiating SLE patients from HCs. CONCLUSIONS: LncRNA ENST00000597482 expression was lower in PBMCs from SLE patients than HCs and was negatively correlated with the SLEDAI-2K score and autoantibody titres. In addition, lncRNA ENST00000597482 could act as a novel biomarker for disease activity and diagnosis of SLE.
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OBJECTIVE: Human gamma-delta T cells (γδ-T cells) play crucial roles in both innate and adaptive immune responses. However, much less is known about the immune status of γδT cells in systemic lupus erythematosus (SLE) patients. The objective of this study was to explore potential relationships between the frequency of γδ-T-cell subpopulations and disease activity, autoantibody titres and renal involvement in patients with SLE. METHODS: Circulating γδ-T cells and their subsets (Vδ1+ T cells, Vδ2+ T cells and γδ-T-cell subpopulations defined by expression of surface receptors, including NKG2D, NKp30, NKp46 and PD-1), were identified via flow cytometry. Sixty active SLE patients were selected, including 41 new-onset and 19 relapsing cases. One hundred healthy controls (HCs) were enrolled as the control group. Percentages of these cell subsets in SLE patients and HCs and their relationships with disease activity were analysed. Twenty-two of the 41 new-onset SLE patients were assessed before and after treatment. Changes in the frequencies of these cell subsets and their relationships with renal involvement were also analysed. RESULTS: Compared with that in HCs, the percentage of total γδ-T cells among CD3+ T cells in SLE patients was significantly lower. An imbalance in the proportions of Vδ1+ and Vδ2+ T cells among γδ-T cells was observed. The proportion of Vδ1+ T cells among γδ-T cells was significantly greater in SLE patients than in HCs, while the proportion of Vδ2+ T cells was significantly lower. Expression levels of PD-1, NKG2D, NKp30 and NKp46 in Vδ1+ T cells and Vδ2+ T cells from SLE patients were generally significantly increased, except for expression of NKG2D in Vδ2+ T cells. Moreover, Vδ2+ T cells, Vδ1+ T cells and Vδ1+PD-1+ T cells were associated with disease activity, and an increase in Vδ2+ T-cell frequency and a decrease in PD-1 expression by γδ-T cells might be associated with effective treatment. Interestingly, our results indicated that Vδ2+ T cells and their Vδ2+NKp30+ T-cell subpopulation might be associated with renal involvement in SLE. CONCLUSION: A broad range of anomalies in the proportions of γδ-T-cell subsets and γδ-T cells in SLE patients may be involved in the pathogenesis of SLE. There is a strong association between Vδ2+ T cells and their Vδ2+NKp30+ T-cell subpopulation and LN occurrence. Our results indicate that γδ-T cells and their subpopulations might be key players in disease immunopathology and renal involvement in SLE.
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Lupus Eritematoso Sistémico , Receptores de Antígenos de Linfocitos T gamma-delta , Humanos , Receptores de Antígenos de Linfocitos T gamma-delta/metabolismo , Subfamilia K de Receptores Similares a Lectina de Células NK/metabolismo , Receptor de Muerte Celular Programada 1/metabolismo , Subgrupos de Linfocitos T , FenotipoRESUMEN
Lithium metal batteries are promising to become a new generation of energy storage batteries. However, the growth of Li dendrites and the volume expansion of the anode are serious constraints to their commercial implementation. Herein, a controllable strategy is proposed to construct an ultrathin 3D hierarchical host of honeycomb copper micromesh loaded with lithiophilic copper oxide nanowires (CMMC). The uniquely designed 3D hierarchical arrayed skeletons demonstrate a surface-preferred and spatial-selective effect to homogenize local current density and relieve the volume expansion, effectively suppressing the dendrite growth. Employing the constructed CMMC current collector in a half-cell, >400 cycles with 99% coulombic efficiency at 0.5 mA cm-2 is performed. The symmetric battery cycles stably for >2000 h, and the full battery delivers a capacity of 166.6 mAh g-1 . This facile and controllable approach provides an effective strategy for constructing high-performance lithium metal batteries.
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Flexible transparent energy supplies are extremely essential to the fast-growing flexible electronic systems. However, the general developed flexible transparent energy storage devices are severely limited by the challenges of low energy density, safety issues, and/or poor compatibility. In this work, a freestanding 3D hierarchical metallic micromesh with remarkble optoelectronic properties (T = 89.59% and Rs = 0.23 Ω sq-1 ) and super-flexibility is designed and manufactured for flexible transparent alkaline zinc batteries. The 3D Ni micromesh supported Cu(OH)2 @NiCo bimetallic hydroxide flexible transparent electrode (3D NM@Cu(OH)2 @NiCo BH) is obtained by a combination of photolithography, chemical etching, and electrodeposition. The negative electrode is constructed by electrodeposition of electrochemically active zinc on the surface of Ni@Cu micromesh (Ni@Cu@Zn MM). The metallic micromesh with 3D hierarchical nanoarchitecture can not only ensure low sheet resistance, but also realize high mass loading of active materials and short electron/ion transmission path, which can guarantee high energy density and high-rate capability of the transparent devices. The flexible transparent 3D NM@Cu(OH)2 @NiCo BH electrode realizes a specific capacity of 66.03 µAh cm-2 at 1 mA cm-2 with a transmittance of 63%. Furthermore, the assembled solid-state NiCo-Zn alkaline battery exhibits a desirable energy density/power density of 35.89 µWh cm-2 /2000.26 µW cm-2 with a transmittance of 54.34%.
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OBJECTIVE: To explore the expression of regulatory B cells (Bregs) in peripheral blood of patients with systemic lupus erythematosus (SLE) and elucidate the function of Bregs in the pathogenesis of SLE. METHODS: A total of 38 active SLE patients, 22 inactive SLE subjects and 20 healthy controls were enrolled. The expressions of IL-10+ CD19+ Breg and CD19+ CD24hi CD38hi Breg in peripheral blood mononuclear cells (PBMC) were evaluated by flow cytometry. And IL-10 was measured in the culture supermatants by enzyme-linked immunosorbent assay (ELISA). RESULTS: The expression of IL-10+ CD19+ Breg in PBMCs of active SLE patients was (1.54±0.64)%. And it was lower than those in inactive SLE patients (2.42±0.75)% (P<0.01) and healthy controls (4.35±1.00)% (P<0.01). And the expression of CD19+ CD24hi CD38hi Breg was (1.26±0.45)%. Also it was lower than those in inactive SLE subjects (2.01±0.61)% (P<0.01) and healthy controls (3.14±0.87)% (P<0.01).The level of IL-10 significantly decreased in culture supermatants of active SLE patients. And it was lower than those in inactive SLE subjects (P<0.05) and healthy controls (P<0.01). The percentage of IL-10+ CD19+ Breg and CD19+ CD24hi CD38hi Breg in PBMCs of SLE patients was positively correlated with the level of IL-10 in culture supernatants (r=0.652, P<0.01 and r=0.574, P<0.01). CONCLUSION: The expression of IL-10-related Bregs significantly decreases in PBMCs of active SLE patients. And Bregs may play some role in the pathogenesis of SLE.
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Linfocitos B Reguladores , Lupus Eritematoso Sistémico , Ensayo de Inmunoadsorción Enzimática , Citometría de Flujo , Humanos , Interleucina-10RESUMEN
Tumor necrosis factor (TNF)-α is one of the major proinflammatory mediators of rheumatic arthritis (RA); the regulatory factors for TNF-α release is not fully understood. This study aims to investigate the role of prolactin receptor (PRLR) activation in regulating the expression and release of TNF-α from CD14(+) monocytes. The results showed that the expression of PRLR was detectable in CD14(+) monocytes of healthy subjects, which was markedly increased in RA patients. Exposure to PRL in the culture increased the expression and release of TNF-α from CD14(+) monocytes, which was abolished by the PRLR gene silencing or blocking the mitogen activated protein (MAPK) pathway. We conclude that exposure to PRL increases TNF-α release from CD14(+) monocytes of RA patients, which can be abolished by PRLR gene silencing or treating with MAPK inhibitor.
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Artritis Reumatoide/inmunología , Monocitos/inmunología , Receptores de Prolactina/genética , Factor de Necrosis Tumoral alfa/biosíntesis , Proteínas Quinasas p38 Activadas por Mitógenos/antagonistas & inhibidores , Flavonoides/farmacología , Regulación de la Expresión Génica/inmunología , Silenciador del Gen , Humanos , Receptores de Lipopolisacáridos/biosíntesis , Sistema de Señalización de MAP Quinasas/inmunología , Prolactina/metabolismo , Inhibidores de Proteínas Quinasas/farmacología , Receptores de Prolactina/inmunología , Factor de Necrosis Tumoral alfa/inmunología , Proteínas Quinasas p38 Activadas por Mitógenos/inmunologíaRESUMEN
OBJECTIVE: To analyze peripheral blood interleukin 6 (IL-6) methylation status and its clinical significance in patients with systemic lupus erythematosus (SLE). MATERIAL AND METHODS: Blood samples from 41 adult patients with SLE, and 20 healthy controls were collected. The methylation status of IL-6 was determined by methylation specific polymerase chain reaction (MSP). The IL-6 expression was detected by real-time PCR. Correlations between IL-6 methylation status and clinical features or laboratory findings in patients with SLE were investigated. RESULTS: The methylation status and expression of IL-6 in peripheral blood could reflect the level in peripheral blood mononucleated cells (PBMCs) of SLE. Significantly positive correlation was found between IL-6 hypomethylation and renal disorder. Interleukin 6 hypomethylation was found negatively correlated with serum C3. CONCLUSIONS: The detection of IL-6 methylation status in peripheral blood could reflect the status in PBMC with SLE. Interleukin 6 may play a role in renal disorder with SLE patients. Interleukin 6 could be considered as a new biomarker for predicting SLE flare.
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Purpose: The study was designed to describe the level of family resilience and identify the protective factors and vulnerability factors of family resilience in families of children with epilepsy. So as to provide theoretical guidance for implementing intervention programs to promote family resilience. Methods: From November 2020 to July 2021, 258 parents of children with epilepsy were investigated using a convenience sampling method. The questionnaire included demographic data, Chinese-Family Resilience Assessment Scale, Social Support Rating Scale, and the Beck Depression Inventory. SPSS25.0 was used for descriptive statistical analysis, univariate analysis, and multivariate linear regression analysis. Results: In this study, two hundred and fifty-eight primary caregivers completed the paper questionnaires. The total score of family resilience was (134.97 ± 16.57), which was above the medium level. Multiple linear regression analysis revealed that subjective support (ß=0.327, P<0.001), comorbidity (ß=0.181, P<0.05), objective support (ß=0.117, P<0.05), and parental depression (ß=-0.158, P<0.05) were significantly related to family resilience. These variables contribute 31.7% of the variance in family resilience (F=18.07, P< 0.001). Conclusion: The families of children with epilepsy presented appropriate resilience after the children were diagnosed with epilepsy. Family resilience was correlated with multiple factors, subjective and objective support could be protective factors, comorbidity and parental depression could be vulnerability factors of family resilience. Therefore, future psychosocial interventions could focus on enhancing subjective support and objective support, reducing parental depression, and screening for epilepsy comorbidity to promote the family resilience of children with epilepsy.
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Objective: This study aimed to investigate the current status of affiliated stigma and caregiver burden among parents of children with epilepsy, analyze their correlation, and identify factors influencing affiliated stigma. Methods: A cross-sectional survey was conducted among 194 parents of children with epilepsy who met the inclusion and exclusion criteria in Shenzhen City, Guangdong Province, China. Data were collected through questionnaires, including a demographic information sheet, an affiliated stigma scale, and a caregiver burden scale. Results: The results revealed that parents of children with epilepsy experienced a moderate level of affiliated stigma, with an average score of 54.92 ± 10.44. Similarly, caregiver burden scores fell within the moderate range, with an average score of 44.14 ± 16.02. Factors influencing affiliated stigma scores included the frequency of epileptic seizures in children, the types of anti-epileptic medications taken by children, and the place of residence. The total caregiver burden score and scores in various dimensions (emotional, cognitive, and behavioral) of caregivers for epilepsy patients were positively correlated with the affiliated stigma score. Affiliated stigma was found to independently explain 21.3 % of the variation in caregiver burden. Conclusion: In the future, healthcare professionals should develop targeted interventions for children with epilepsy and their parents to reduce affiliated stigma, decrease caregiver burden, and enhance the caregiving capabilities of parents of children with epilepsy. These measures are essential to improve the overall well-being of both parents and children affected by epilepsy.
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OBJECTIVE: To explore the significance and evaluate the early structural erosion through the expressions of Th17 cells in peripheral blood of patients with rheumatoid arthritis (RA) in clinical remission. METHODS: A total of 41 active RA patients without structural erosion were selected. Intracelluar flow cytometric detection of Th17 cells in peripheral blood was performed. And the supernatant level of interleukin (IL)-17A was determined simultaneously in RA patients and control groups at baseline and endpoint of 24-month therapy. The correlations were analyzed between Th17 cells and RA disease activity index DAS28. They were classified into radiographic progression (P, n = 10) and radiographic non-progression groups (NP, n = 26) by the Sharp/van der Heijde score (SHS) at the endpoint. The differences of Th17 cells and IL-17A levels were analyzed between P (SHS > 0.5) and NP groups (SHS ≤ 0.5). RESULTS: The expression of Th17 cells in active RA patients was significantly higher than that of controls [(1.63 ± 0.45)% vs (0.91 ± 0.26)%, P < 0.01]. And the results of IL-17A level were similar [1510 ± 280) vs (320 ± 31) ng/L, P < 0.05]. The expression of Th17 cells was positively correlated with DAS28 score (r = 0.87, P < 0.01). Thirty-six RA patients were followed up at the endpoint and all of them stayed in clinical remission (DAS28 < 2.6). The peripheral blood expressions of Th17 cells of P group were significantly higher than those of NP group . At the same time, no differences of IL-17A levels existed between two groups. CONCLUSION: Structural erosion still progresses in some RA patients despite an apparent clinic remission. And a high-level peripheral expression of Th17 hints at structural erosion.
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Artritis Reumatoide/sangre , Interleucina-17/sangre , Células Th17/metabolismo , Adulto , Estudios de Casos y Controles , Progresión de la Enfermedad , Femenino , Citometría de Flujo , Humanos , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVE: To explore the expression and significance of Th17 and Treg cells in peripheral blood of patients with systemic lupus erythematosus (SLE). METHODS: Thirty active SLE patients (including 17 SLE patients with lupus nephritis), 20 inactive SLE patients and 20 healthy controls were enrolled. The expressions of Th17 cells and CD4+CD25+Foxp3+Treg cells in peripheral blood mononuclear cells (PBMC) were evaluated by flow cytometry. The correlations between the expression of Th17 cells, CD4+CD25+Foxp3+Treg cells and disease activity (SLEDAI), as well as the ratios of Th17 cells and Treg cells (Th17/Treg) in SLE patients and healthy controls were analyzed respectively. RESULTS: The expression of Th17 cells in PBMC of SLE patients was higher than that in healthy controls [(1.39 ± 0.60)% vs (0.80 ± 0.33)%, P < 0.01] while the expression of CD4+CD25+Foxp3+Treg cells decreased in SLE patients [(3.09 ± 1.54)% vs (6.04 ± 1.49)%, P < 0.01]. The increased expression of Th17 cells and reduced CD4+CD25+Foxp3+Treg cells in PBMC were positively correlated with SLEDAI and negatively correlated with complements C3 and C4. There were increased expression of Th17 cells and reduced CD4+CD25+Foxp3+Treg cells in PBMC of lupus nephritis versus SLE patients without nephritis. CONCLUSION: There is an abnormal elevation of Th17 cells and decrease of CD4+CD25+Foxp3+Treg cells in PBMC of SLE patients. The imbalance between Th17 and Treg cells may play a critical role in the pathogenesis of SLE.
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Lupus Eritematoso Sistémico/inmunología , Linfocitos T Reguladores/inmunología , Células Th17/inmunología , Adolescente , Adulto , Estudios de Casos y Controles , Femenino , Citometría de Flujo , Factores de Transcripción Forkhead , Humanos , Subunidad alfa del Receptor de Interleucina-2 , Lupus Eritematoso Sistémico/sangre , Nefritis Lúpica/sangre , Nefritis Lúpica/inmunología , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
Purpose: This study was designed to assess the effects of epilepsy severity, family resilience, and social support on depression in primary caregivers of children with epilepsy (CWE), and to test the mediating roles of family resilience and social support in this relationship. Method: Two hundred fifty-two caregivers of children with epilepsy were recruited from October 2020 to May 2021. The questionnaire contained sociodemographic characteristics, Epilepsy Severity, Chinese-Family Resilience Assessment Scale (C-FRAS), Social Support Rating Scale (SSRS), Beck Depression Inventory (BDI). Structural equation models were used to evaluate whether family resilience and social support as mediators between epilepsy severity and depression. Results: In this study, the prevalence of depressive symptoms among primary caregivers of CWE in China was 69.84%. Epilepsy severity was positively associated with depression. Family resilience and social support were negatively correlated with depressive symptoms (both p < 0.01). Furthermore, the fitness indices of structural models were satisfactory. The direct effect of epilepsy severity on depression was 0.266 (95% CI 0.064-0.458), this pathway explained 62.88% variance of depression. The indirect effect of family resilience and then social support was 0.069 (95% CI 0.025-0.176), indicating that the serial multiple mediation was significant. The serial mediation pathway explained 16.31% variance of depression. Conclusions: The high incidence of depression among primary carers of CWE deserves more attention. They should be screened routinely, especially those parents of children with severe epilepsy. Family resilience and social support could be protective factors for caregivers' mental adjustment. Therefore, future psychosocial interventions for enhancing family resilience and social support should be implemented, in order to reduce their depression.
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OBJECTIVE: T cells display significant phenotypical changes and play multiple roles in promoting the immune response in SLE. The frequencies of T cell subpopulations in SLE are still not well understood. To better understanding the phenotypic abnormalities of T cells in SLE will help us to clarify disease immunopathology and to find promising biomarkers for disease monitoring and control. METHODS: Peripheral blood CD4+ and CD8+ T cells and their subsets were determined by flow cytometry. Forty-one active SLE patients were selected, including 28 new-onset patients and 13 relapsing patients. One hundred healthy controls (HCs) were enrolled as the control group. The percentages of these cell subsets between patients with SLE and HCs and their relationships with disease activity and autoantibody titers were analysed. Thirteen of 28 new-onset SLE patients were assessed before and after treatment. The changes in the frequencies of these cell subsets and their relationships with renal response were analysed. RESULTS: There was a broad range of anomalies in the proportion of T cell subsets in patients with SLE compared with that of the HCs. Compared with the HCs, a higher frequency of memory T cells and a lower frequency of naïve T cells were noted in patients with SLE. In addition, an imbalance of CD28+ and CD28- cells in CD4+ T cells was observed in patients with SLE. We found that the expanded CD4+CD28- T cells did not decrease after treatment in patients who had impaired renal responses. It was very interesting to exhibit a negative correlation in the frequency between the CD4+CD28- T cells and T regulatory (Treg) cells and a positive correlation between the frequency of CD4+CD28+ T cells and Treg cells in this study. Increased CD8+HLADR+ T cell and CD8+CD38+HLADR+ T cell counts were observed in patients with SLE, suggesting an impaired cytotoxic capacity of CD8+ T cells in SLE. Additionally, we found that CD8+CD38+HLADR+ T cells were closely associated with disease activity, autoantibody titres and renal prognosis. CD4+ CXCR5-PD1+ T cells were expanded in patients with SLE in this study and were associated with disease activity in SLE. Th1 (T helper type 1) cells and Treg cells were decreased, but frequencies of T follicular helper (Tfh) cells, Th2 cells, Th17 cells and Tfh17 cells were increased. A strong correlation between Th17 cells and Tregs with renal involvement was observed in this study. CONCLUSION: The proportions of CD4+CD28- T cells, CD4+CXCR5-PD1+ T cells, CD8+HLADR+ T cells and CD8+CD38+HLADR+ T cells increased in patients with SLE and could be associated with disease activity and renal prognosis.
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Linfocitos T CD4-Positivos , Linfocitos T CD8-positivos , Lupus Eritematoso Sistémico , Antígenos CD28/metabolismo , Linfocitos T CD4-Positivos/citología , Linfocitos T CD8-positivos/citología , Humanos , Lupus Eritematoso Sistémico/inmunología , Subgrupos de Linfocitos T , Linfocitos T Reguladores/citologíaRESUMEN
PURPOSE: To evaluate the retention rate, efficacy, and safety of ketogenic diet therapy for drug-resistant epilepsy in children and compare the results with those of a previous cohort at our institution. METHODS: A total of 634 children with drug-resistant epilepsy were included in this retrospective study. Patients were categorized into two groups. The previous cohort was included as a control group and included 317 children assessed between 2004 and 2011, whereas the current group included 317 children assessed between 2015 and 2019. The control group was provided care as usual, and the current group additionally adopted the goal and long-term management strategy. Outcomes were measured with respect to retention rate, seizure reduction, and adverse reaction. RESULTS: Patient demographics were consistent between both cohorts. Compared to the past ten years, the retention rate significantly increased over time (3 months: 62.8% vs. 82.0%, p <0.001; 6 months: 42.0% vs. 60.6%, p <0.001; 12 months: 24.3% vs. 34.1%, p = 0.007), and the response rate was significantly improved (3 months: 35.0% vs. 55.5%, p <0.001; 6 months: 26.2% vs. 43.2%, p <0.001; 12 months: 18.6% vs. 31.5%, p <0.001). Constipation (n = 79, 24.9%) was the most common side effect in the current cohort. Food refusal and hypoproteinaemia reduced to 3.5% and 0.9%, respectively. CONCLUSION: Goal and long-term management is effective for ketogenic diet therapy, which significantly improved the ketogenic diet retention rate, efficacy, and incidence of adverse reactions. This strategy has promising applicability in ketogenic diet therapy. CLINICAL REGISTRATION: ChiCTR-IIR-16,008,342.
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Dieta Cetogénica , Epilepsia Refractaria , Preparaciones Farmacéuticas , Niño , Humanos , Estudios Retrospectivos , Convulsiones , Resultado del TratamientoRESUMEN
Introduction: Glaucoma is a chronic disease that requires long-term adherence to treatment. Topical application of conventional eye drops results in substantial drug loss due to rapid tear turnover, with poor drug bioavailability being a major challenge for efficient glaucoma treatment. We aimed to prepare the anti-glaucoma drug betaxolol hydrochloride (BH) as a novel nano-delivery system that prolonged the retention time at the ocular surface and improved bioavailability. Methods: We constructed multifunctional nanoparticles (MMt-BH-HA/CS-ED NPs) by ion cross-linking-solvent evaporation method. The particle size, zeta potential, encapsulation efficiency and drug loading of MMt-BH-HA/CS-ED NPs were physicochemically characterized. The structure of the preparations was characterized by microscopic techniques of SEM, TEM, XPS, XRD, FTIR and TGA, and evaluated for their in vitro release performance as well as adhesion properties. Its safety was investigated using irritation assays of hemolysis experiment, Draize test and histopathology examination. Precorneal retention was examined by in vivo fluorescence tracer method and pharmacokinetics in tear fluid was studied. A model of high IOP successfully induced by injection of compound carbomer solution was used to assess the IOP-lowering efficacy of the formulation, and it was proposed that micro-interactions between the formulation and the tear film would be used to analyze the behavior at the ocular surface. Results: The positively charged MMt-BH-HA/CS-ED NPs were successfully prepared with good two-step release properties, higher viscosity, and slower pre-corneal diffusion rate along with longer precorneal retention time compared to BH solution. The micro-interactions between nanoparticles and tear film converted the drug clearance from being controlled by fast aqueous layer turnover to slow mucin layer turnover, resulting in higher drug concentration on the ocular surface, providing more durable and stable IOP-lowering efficacy. Conclusion: The novel multifunctional MMt-BH-HA/CS-ED NPs can effectively reduce IOP and are suitable for the treatment of chronic disease glaucoma.
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Glaucoma , Nanopartículas , Humanos , Betaxolol , Presión Intraocular , Nanopartículas/química , Glaucoma/patología , Córnea , Tamaño de la Partícula , Portadores de Fármacos/químicaRESUMEN
To evaluate the association of inflammatory markers and depression in RA patients and the risk factors in RA with depression, a cross-sectional study was conducted in a cohort of RA patients from southern China.Two hundred-fifteen RA patients were enrolled. The demographic and disease-related characteristics were recorded and inflammatory markers in sera were measured. RA patients were guided to fill out PHQ-9 scale by themselves, the psychological state was evaluated by psychiatry experts and graded according to the HAMD-17 scale. The consistency of the two scales in judging depression was evaluated. RA with depression group had HAMD-17 scores greater than 7. The levels of CRP, ESR, fibrinogen, SAA, IL-2, IL-6, TNF-α, IFN-γ, IL-4, and IL-10 were measured and compared. Logistic regression analysis was performed to find the risk factors of RA with different depression levels. One hundred-five (48.84%) RA patients had HAMD-17 scores greater than 7. High consistency was found between HAMD-17 and PHQ-9 in predicting depression. RA patients with depression were more likely to have tender joints, lower income, no employment, higher disease activity, joint deformities and glucocorticoid treatment. The depressed RA patients had higher serum levels of IL-6, CRP, fibrinogen, and SAA. IL-6, CRP, fibrinogen, and SAA were positive correlated with depression in RA patients. PHQ-9 can replace HAMD-17 in clinical application to judge depression.
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Artritis Reumatoide , Artritis Reumatoide/tratamiento farmacológico , Biomarcadores , Proteína C-Reactiva/análisis , Estudios Transversales , Depresión/diagnóstico , Fibrinógeno/análisis , Humanos , Interleucina-6 , Factores de RiesgoRESUMEN
BACKGROUND: This study aimed to investigate the relationship between myonectin levels and metabolic and hormonal disorders in patients with polycystic ovary syndrome (PCOS). METHODS: One hundred PCOS patients who sought medical advice from September 2017 to March 2019 in our hospital were selected as the PCOS group, while 100 healthy women matched for age and body mass index (BMI) with the PCOS patients were selected as the control group. General clinical information, myonectin levels, and metabolism and sex hormone-related indicators of the two groups were compared, and the correlation between myonectin, metabolism, and sex hormones was analyzed. RESULTS: There were no significant differences in age, BMI, blood pressure, or other general clinical information between the two groups (P>0.05). Compared with the control group, the levels of myonectin, sex hormone-binding globulin (SHBG), and high-density lipoprotein cholesterol (HDL-C) in the PCOS group were significantly decreased (P<0.05), while the levels of fasting blood glucose (FBG), homeostasis model assessment of insulin resistance (HOMA-IR), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), luteinizing hormone (LH), and testosterone were significantly increased (P<0.05). Pearson correlation analysis showed that the level of myonectin was negatively correlated with BMI, FBG, HOMA-IR, TG, and testosterone but was positively correlated with SHBG and HDL-C. Multivariate linear regression analysis showed that the level of myonectin was negatively correlated with BMI, HOMA-IR, and TG but positively correlated with SHBG and HDL-C. CONCLUSIONS: There is a correlation between the level of myonectin and multiple metabolic and hormone indices in PCOS patients indicating that myonectin may be an effective index to predict metabolic and hormone disorders in PCOS patients.
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Síndrome del Ovario Poliquístico , Índice de Masa Corporal , Estudios de Casos y Controles , HDL-Colesterol , Femenino , Humanos , Hormona Luteinizante , TriglicéridosRESUMEN
The genus Pisolithus is a group of global ectomycorrhizal fungi. The characterizations of Pisolithus mitochondrial genomes have still been unknown. In the present study, the complete mitogenomes of two Pisolithus species, Pisolithus microcarpus, and Pisolithus tinctorius, were assembled and compared with other Boletales mitogenomes. Both Pisolithus mitogenomes comprised circular DNA molecules with sizes of 43,990 and 44,054 bp, respectively. Comparative mitogenomic analysis showed that the rps3 gene differentiated greatly between Boletales species, and this gene may be subjected to strong pressure of positive selection between some Boletales species. Several plasmid-derived genes and genes with unknown functions were detected in the two Pisolithus mitogenomes, which needs further analysis. The two Pisolithus species show a high degree of collinearity, which may represent the gene arrangement of the ancestors of ectomycorrhizal Boletales species. Frequent intron loss/gain events were detected in Boletales and basidiomycetes, and intron P717 was only detected in P. tinctorius out of the eight Boletales mitogenomes tested. We reconstructed phylogeny of 79 basidiomycetes based on combined mitochondrial gene dataset, and obtained well-supported phylogenetic topologies. This study served as the first report on the mitogenomes of the family Pisolithaceae, which will promote the understanding of the evolution of Pisolithus species.
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In this study, the mitogenome of artillery fungus, Sphaerobolus stellatus, was assembled and compared with other Basidiomycota mitogenomes. The Sphaerobolus stellatus mitogenome was composed of circular DNA molecules, with a total size of 152,722 bp. Accumulation of intergenic and intronic sequences contributed to the Sphaerobolus stellatus mitogenome becoming the fourth largest mitogenome among Basidiomycota. We detected large-scale gene rearrangements in Basidiomycota mitogenomes, and the Sphaerobolus stellatus mitogenome contains a unique gene order. The quantity and position classes of intron varied between 75 Basidiomycota species we tested, indicating frequent intron loss/gain events occurred in the evolution of Basidiomycota. A novel intron position classes (P1281) was detected in the Sphaerobolus stellatus mitogenome, without any homologous introns from other Basidiomycota species. A pair of fragments with a total length of 9.12 kb in both the nuclear and mitochondrial genomes of Sphaerobolus stellatus was detected, indicating possible gene transferring events. Phylogenetic analysis based on the combined mitochondrial gene set obtained well-supported tree topologies (Bayesian posterior probabilities ≥ 0.99; bootstrap values ≥98). This study served as the first report on the mitogenome from the order Geastrales, which will promote the understanding of the phylogeny, population genetics, and evolution of the artillery fungus, Sphaerobolus stellatus.
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OBJECTIVE: There is evidence that interleukin-6 (IL-6) upregulation plays a critical role in immunopathology of systemic lupus erythematosus (SLE). MicroRNA- (miRNA-) 98 was predicted to bind with the 3'-untranslated region (3'-UTR) of IL-6 gene. We hypothesized miR-98 through its regulation of IL-6 gene expression to influence cytokine production from peripheral blood mononuclear cells (PBMCs) in SLE. METHODS: The expression of miR-98 and IL-6 mRNA in the PBMCs of 41 SLE patients and 20 healthy controls (HC) was detected by quantitative reverse transcription PCR (qRT-PCR). The correlations between miR-98 expression and clinical features were evaluated. Luciferase reporter assay was performed to identify miR-98 targets. miR-98 mimics, miR-98 inhibitor, and IL-6 overexpression vector were generated. Cell viability of PBMCs was assessed using MTT assay. Gene expression and protein level were determined by qRT-PCR and Western blotting. TNF-α, IL-8, IL-1ß, and IL-10 levels in cultured supernatants were quantified using ELISA. RESULTS: The expression of miR-98 was downregulated in PBMCs of SLE patients, and its expression is negatively associated with IL-6 levels. miR-98 expression was correlated with disease activity, lupus nephritis, and anti-dsDNA antibody. IL-6 mRNA was a target gene of miR-98. IL-6 overexpression promoted the proliferation of PBMCs and increased the levels of TNF-α, IL-8, IL-1ß, and IL-10. Those effects were further enhanced by miR-98 inhibitor, while were suppressed by miR-98 mimics. miR-98 regulated the levels of STAT3 phosphorylation via its target gene IL-6. CONCLUSION: The current study revealed that miR-98 could ameliorate STAT3-mediated cell proliferation and inflammatory cytokine production via its target gene IL-6 in patients with SLE. These results suggest that miR-98 might serve as a potential target for SLE treatment and other IL-6-mediated diseases.