RESUMEN

BACKGROUND: Abnormal biological behaviour of keratinocytes (KCs) is a critical pathophysiological manifestation of psoriasis. Ferroptosis is programmed cell death induced by the accumulation of lipid reactive oxygen species (ROS) in the presence of increased intracellular iron ions or inhibition of GPX4. OBJECTIVES: The purpose of this study was to investigate the effects of ferroptosis on the biological behaviour of Keratinocytes (KCs) in psoriasis vulgaris and its possible regulatory mechanisms in clinical samples, cells, and mouse models. METHODS: We first examined the differences in the expression of GPX4 and 4-HNE between psoriasis and normal human lesions. And detected KRT6, FLG, and inflammatory cytokines after inducing ferroptosis in animal and cell models by RT-qPCR, Western blot, immunohistochemistry, and flow cytometry. RESULTS: We found that GPX4 was decreased and that the oxidation product 4-hydroxy-2-nonenal (HNE) was increased in the skin lesions of patients with psoriasis vulgaris. The expression level of GPX4 correlates with the severity of skin lesions. Moreover, inducing ferroptosis promoted the expression of FLG and reduced the expression of KRT6 and inflammatory cytokines in vitro, and alleviated the phenotype of skin lesions in vivo. LIMITATIONS: Our study has limitations, notably small sample size. Larger clinical trials are necessary to investigate the association between ferroptosis and disease progression further. More research is necessary to explore how the ferroptosis inducer RSL3 regulates the abnormal biological behaviour of KCs at both cellular and animal levels and establish ferroptosis inhibitors as controls. CONCLUSIONS: This study confirms the existence of ferroptosis in psoriatic lesions, which may be inversely correlated with disease severity. The ferroptosis inducer RSL3 ameliorated psoriatic symptoms by improving the abnormal biological behaviour of KCs.

Asunto(s)

Modelos Animales de Enfermedad , Ferroptosis , Queratinocitos , Fosfolípido Hidroperóxido Glutatión Peroxidasa , Psoriasis , Psoriasis/patología , Psoriasis/metabolismo , Psoriasis/inmunología , Ferroptosis/fisiología , Queratinocitos/metabolismo , Queratinocitos/patología , Humanos , Animales , Ratones , Proyectos Piloto , Fosfolípido Hidroperóxido Glutatión Peroxidasa/metabolismo , Fosfolípido Hidroperóxido Glutatión Peroxidasa/genética , Aldehídos/metabolismo , Femenino , Masculino , Adulto , Queratina-6/metabolismo , Citocinas/metabolismo , Piel/patología , Piel/metabolismo , Piel/inmunología , Persona de Mediana Edad , Resorcinoles/farmacología , Especies Reactivas de Oxígeno/metabolismo , Carbolinas

RESUMEN

Pompe disease (PD) is a rare autosomal recessive glycogen storage disorder that causes proximal muscle weakness and loss of respiratory function. While enzyme replacement therapy (ERT) is the only effective treatment, biomarkers for disease monitoring are scarce. Following ex vivo biomarker validation in phantom studies, we apply multispectral optoacoustic tomography (MSOT), a laser- and ultrasound-based non-invasive imaging approach, in a clinical trial (NCT05083806) to image the biceps muscles of 10 late-onset PD (LOPD) patients and 10 matched healthy controls. MSOT is compared with muscle magnetic resonance imaging (MRI), ultrasound, spirometry, muscle testing and quality of life scores. Next, results are validated in an independent LOPD patient cohort from a second clinical site. Our study demonstrates that MSOT enables imaging of subcellular disease pathology with increases in glycogen/water, collagen and lipid signals, providing higher sensitivity in detecting muscle degeneration than current methods. This translational approach suggests implementation in the complex care of these rare disease patients.

Asunto(s)

Enfermedad del Almacenamiento de Glucógeno Tipo II , Glucógeno , Imagen por Resonancia Magnética , Técnicas Fotoacústicas , Humanos , Enfermedad del Almacenamiento de Glucógeno Tipo II/diagnóstico por imagen , Enfermedad del Almacenamiento de Glucógeno Tipo II/metabolismo , Enfermedad del Almacenamiento de Glucógeno Tipo II/patología , Glucógeno/metabolismo , Técnicas Fotoacústicas/métodos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Imagen por Resonancia Magnética/métodos , Músculo Esquelético/diagnóstico por imagen , Músculo Esquelético/metabolismo , Músculo Esquelético/patología , Estudios de Casos y Controles , Ultrasonografía/métodos , Fantasmas de Imagen

RESUMEN

The pattern of itching in patients with atopic dermatitis has not been systematically studied. Therefore, this study aimed to assess the pattern of itching in adults with atopic dermatitis using questionnaires to assess for a circadian rhythm of itching in participating patients at a single institution (n = 241). A self-report questionnaire was used to assess circadian rhythm and intensity of itching in patients. In addition, the patients' disease severity (Eczema Area and Severity Index [EASI]) and quality of life (Dermatology Life Quality Index [DLQI]) were assessed. Itching occurred most frequently (74.69%) and with the greatest severity (62.66%) between 20:00 and 00:00, and the least number of patients (25.31%) experienced itching between 04:00 and 08:00. The DLQI and EASI scores both correlated with the average and maximum itch intensity (r = 0.582, r = 0.533, respectively; r = 0.539, r = 0.517, respectively; p < 0.001). The DLQI and EASI scores were associated with average itch intensity (B = 0.179, B = 0.204, respectively; 95% CI: 0.112 to 0.246, 95% CI: 0.096 to 0.313, respectively; p < 0.001), and the EASI score was associated with males and family history (B = 0.285, B = 0.287, respectively; 95% CI: 0.094 to 0.476, 95% CI: 0.096 to 0.478, respectively; p = 0.003). Adult patients with atopic dermatitis exhibited a circadian rhythm of itching; these study results could positively impact treatment approaches.

Asunto(s)

Ritmo Circadiano , Dermatitis Atópica , Prurito , Calidad de Vida , Índice de Severidad de la Enfermedad , Humanos , Dermatitis Atópica/fisiopatología , Dermatitis Atópica/complicaciones , Dermatitis Atópica/diagnóstico , Prurito/fisiopatología , Prurito/etiología , Prurito/diagnóstico , Masculino , Femenino , Adulto , Estudios Transversales , Persona de Mediana Edad , Adulto Joven , Factores de Tiempo , Encuestas y Cuestionarios , Autoinforme , Anciano , Adolescente

RESUMEN

BACKGROUND: Alopecia affects patients' appearance and psychology. Mixed-lineage kinase domain-like pseudokinase (MLKL)-mediated necroptosis plays a role in various skin diseases, but its effect on hair growth is unclear. OBJECTIVE: To investigate the effects of MLKL on hair growth and its regulatory mechanisms and to determine the potential clinical value of Necrosulfonamide (NSA, a MLKL-targeting inhibitor) in promoting hair growth and counteracting dihydrotestosterone (DHT) inhibition of hair growth. METHODS: The expression level of MLKL was detected in the scalp of androgenetic alopecia (AGA) patients and the skin tissues of mice. Knock down MLKL expression or use NSA to observe hair growth in vivo and in vitro. RESULTS: In AGA patients, MLKL expression is elevated in the alopecia areas. In mice, MLKL is significantly expressed in the outer root sheath (ORS) cells of hair follicles, peaking during the catagen phase. Knockdown expression of MLKL in mice skin promoted hair growth. NSA enhanced hair growth and prevented hair follicle regression via the Wnt signaling. Reduced MLKL boosts ORS cell proliferation without directly impacting DPCs' growth. Interestingly, NSA boosts DPCs' proliferation and induction when co-cultured with ORS cells. Besides, NSA alleviated the inhibition of DHT on hair growth in vivo and vitro. CONCLUSION: NSA inhibited the activation of MLKL in ORS cells, promoted the activation of Wnt signal in DPC cells, and improved the inhibition of hair growth by DHT, illuminating a new alopecia mechanism and aiding anti-alopecia drug development.

Asunto(s)

Alopecia , Proliferación Celular , Dihidrotestosterona , Folículo Piloso , Proteínas Quinasas , Sulfonamidas , Animales , Alopecia/tratamiento farmacológico , Alopecia/patología , Ratones , Folículo Piloso/efectos de los fármacos , Folículo Piloso/crecimiento & desarrollo , Folículo Piloso/metabolismo , Humanos , Dihidrotestosterona/farmacología , Sulfonamidas/farmacología , Masculino , Proliferación Celular/efectos de los fármacos , Proteínas Quinasas/metabolismo , Proteínas Quinasas/genética , Cabello/crecimiento & desarrollo , Cabello/efectos de los fármacos , Vía de Señalización Wnt/efectos de los fármacos , Modelos Animales de Enfermedad , Femenino , Adulto , Cuero Cabelludo/efectos de los fármacos , Ratones Endogámicos C57BL

RESUMEN

BACKGROUND: Confocal laser scanning microscopy (CLSM) is noninvasive technique utilized for identification and analysis skin malignancies. Several studies have applied CLSM in monitoring the therapeutic effects of basal cell carcinoma (BCC). OBJECTIVE: To investigate the diagnostic value of CLSM in low-risk BCC and the evaluation of photodynamic therapy (PDT). METHODS: We have diagnosed 149 patients with BCC using CLSM and histopathological examination. Based on histopathology, we summarized the classification information of low-risk BCC along with imaging features observed through CLSM. Thirty-four low-risk BCC patients underwent PDT treatment, and we used CLSM to evaluate its efficacy. RESULTS: Out of 149 participants were diagnosed with BCC by CLSM, 52 were pigmented type, 87 were nodular type and 10 were superficial type. After histopathological examination, 44 out of 52 were pigmented type, five were nodular type and three were superficial type. The results of CLSM were consistent with those of 87 nodular type and 10 superficial type. The CLSM features of nodular were observed in the tissue fissures around the tumor, the pigment mass was the CLSM characteristic of pigmented type. The simultaneous occurrence of inflammation and increased vasculature were characteristics of superficial. The effective rate of PDT was 100%, and the cure rate was 67.6%. At 12 months follow up, the recurrence rate of PDT was 11.8%, 15.0% for nodule type, 10.0% for pigmented type and 0% for superficial type. CONCLUSION: The tissue classification of CLSM for low-risk BCC was consistent with histopathology. CLSM can be used to monitor the efficacy of PDT for low-risk BCC.

RESUMEN

RATIONALE: Thrombotic thrombocytopenic purpura (TTP) is a syndrome characterized by widespread blood vessel clotting and bleeding. It can affect individuals of any age but is more commonly observed in females, particularly during pregnancy. Pregnancy combined with TTP is a critical and rapidly progressing condition that is often misdiagnosed as an obstetric disorder like severe preeclampsia or HELLP syndrome. To deepen the understanding of TTP during pregnancy with the help of a clinical case. PATIENT CONCERNS: A 20-year-old patient, is pregnancy 1 birth 0, 32 weeks dated by her last menstrual period, presented chest tightness, and shortness of breath after physical activity for 3 days. DIAGNOSES: TTP. INTERVENTIONS: At present, there are no preventive measures. Timely diagnosis and treatment are useful. Plasma exchange and treat to the patient hinder autoantibodies, such as gamma globulin, methylprednisolone, rituximab, and cyclosporine were effective. OUTCOMES: The patient exhibited stable vital signs, normal examination results, and experienced no complications. We continued to monitor her progress after she was discharged. LESSONS SUBSECTIONS: The acute onset of TTP is often associated with pregnancy, as it is a triggering factor. Timely identification, accurate diagnosis, and a comprehensive treatment approach involving plasma exchange, immunosuppressants, and the termination of pregnancy can lead to remission and a favorable outlook for the majority of patients.

Asunto(s)

Intercambio Plasmático , Complicaciones Hematológicas del Embarazo , Púrpura Trombocitopénica Trombótica , Humanos , Femenino , Embarazo , Púrpura Trombocitopénica Trombótica/diagnóstico , Púrpura Trombocitopénica Trombótica/terapia , Púrpura Trombocitopénica Trombótica/complicaciones , Intercambio Plasmático/métodos , Adulto Joven , Complicaciones Hematológicas del Embarazo/diagnóstico , Complicaciones Hematológicas del Embarazo/terapia

RESUMEN

High-quality perovskite films are essential for achieving high performance of optoelectronic devices; However, solution-processed perovskite films are known to suffer from compositional and structural inhomogeneity due to lack of systematic control over the kinetics during the formation. Here, the microscopic homogeneity of perovskite films is successfully enhanced by modulating the conversion reaction kinetics using a catalyst-like system generated by a foaming agent. The chemical and structural evolution during this catalytic conversion is revealed by a multimodal synchrotron toolkit with spatial resolutions spanning many length scales. Combining these insights with computational investigations, a cyclic conversion pathway model is developed that yields exceptional perovskite homogeneity due to enhanced conversion, having a power conversion efficiency of 24.51% for photovoltaic devices. This work establishes a systematic link between processing of precursor and homogeneity of the perovskite films.

RESUMEN

Type 2 inflammation related diseases, such as atopic dermatitis, asthma, and allergic rhinitis, are diverse and affect multiple systems in the human body. It is common for individuals to have multiple co-existing type 2 inflammation related diseases, which can impose a significant financial and living burden on patients. However, the exact pathogenesis of these diseases is still unclear. The NLRP3 inflammasome is a protein complex composed of the NLRP3 protein, ASC, and Caspase-1, and is activated through various mechanisms, including the NF-κB pathway, ion channels, and lysosomal damage. The NLRP3 inflammasome plays a role in the immune response to pathogens and cellular damage. Recent studies have indicated a strong correlation between the abnormal activation of NLRP3 inflammasome and the onset of type 2 inflammation. Additionally, it has been demonstrated that suppressing NLRP3 expression effectively diminishes the inflammatory response, highlighting its promising therapeutic applications. Therefore, this article reviews the role of NLRP3 inflammasome in the development and therapy of multiple type 2 inflammation related diseases.

Asunto(s)

Inflamasomas , Proteína con Dominio Pirina 3 de la Familia NLR , Humanos , Inflamasomas/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , FN-kappa B/metabolismo , Inflamación/metabolismo , Caspasa 1/metabolismo

RESUMEN

Lung cancer is the leading cause of cancer-related deaths worldwide, of which non-small cell lung cancer (NSCLC) is the most common type, and epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are widely used for the treatment of NSCLC. EGFR-TKIs are known to develop a drug-resistant response after a certain number of cycles of dosing, and how to alleviate or even reverse EGFR-TKI resistance is an urgent problem at present. This review focuses on the role of ncRNAs in the resistance of NSCLC to EGFR-TKIs and the potential mechanisms underlying the development of NSCLC resistance to EGFR-TKIs. NcRNAs are involved in NSCLC resistance to EGFR-TKIs by mediating cellular drug efflux, epithelial-mesenchymal transition, apoptosis, autophagy, and EGFR mutation. ncRNAs play a crucial role in NSCLC resistance to EGFR-TKIs. Hopefully, the results will provide some guidance and help for the treatment and prognosis of NSCLC.

RESUMEN

Peripheral arterial disease (PAD) leads to chronic vascular occlusion and results in end organ damage in critically perfused limbs. There are currently no clinical methods available to determine the muscular damage induced by chronic mal-perfusion. This monocentric prospective cross-sectional study investigated n = 193 adults, healthy to severe PAD, in order to quantify the degree of calf muscle degeneration caused by PAD using a non-invasive hybrid ultrasound and single wavelength optoacoustic imaging (US/SWL-OAI) approach. While US provides morphologic information, SWL-OAI visualizes the absorption of pulsed laser light and the resulting sound waves from molecules undergoing thermoelastic expansion. US/SWL-OAI was compared to multispectral data, clinical disease severity, angiographic findings, phantom experiments, and histological examinations from calf muscle biopsies. We were able to show that synergistic use of US/SWL-OAI is most likely to map clinical degeneration of the muscle and progressive PAD.

RESUMEN

In perovskite solar cells (PSCs), tin dioxide (SnO2) is a highly effective electron transport material. On the other hand, the low intrinsic conductivity of SnO2, the high trap-state density on the surface and bulk of SnO2, and inadequate interface contacts between SnO2 and perovskite significantly impact device performance. Herein, small-molecule copper(II) chloride (CuCl2) is introduced into the SnO2 dispersion, which inhibits the agglomeration of SnO2 colloids and improves the quality of the electron transport layer. Furthermore, the introduction of CuCl2 optimizes the energy-level array between the ETL and perovskite layer (PVK) and passivates the anion/cation defects in SnO2, perovskite, and their interface, realizing the systematic modulation of the photoelectronic properties of the ETLs and PVKs as well as the PVK/ETL. As a result, the CuCl2-opmized PSC exhibits an impressive power conversion efficiency of 23.71%, along with improved stability.

RESUMEN

Due to the uniqueness and interactivity of its scenario, the cultural and tourism commercial space consistently enriches and enhances the user experience while satisfying users' consumption and shopping. However, there is limited research on the participatory aspect of cultural tourism business spaces from the perspective of users. To this end, the present study investigates the participatory experience of cultural tourism commercial spaces by selecting 305 tourists who visited Huaihai Street in Suzhou for consumption and entertainment and quantifies the relationship between the public's flow experience, aesthetic judgments, and behavioral outcomes using a structural equation modeling approach. The results of the study confirm that aesthetic judgments and flow experiences positively impact behavioral outcomes and that flow experiences also affect aesthetic judgments and behavioral outcomes. These findings contribute to a better understanding of the significance of user participation in cultural tourism business spaces.

RESUMEN

The best research-cell efficiency of perovskite solar cells (PSCs) is comparable with that of mature silicon solar cells (SSCs); However, the industrial development of PSCs lags far behind SSCs. PSC is a multiphase and multicomponent system, whose consequent interfacial energy loss and carrier loss seriously affect the performance and stability of devices. Here, by using spinodal decomposition, a spontaneous solid phase segregation process, in situ introduces a poly(3-hexylthiophene)/perovskite (P3HT/PVK) heterointerface with interpenetrating structure in PSCs. The P3HT/PVK heterointerface tunes the energy alignment, thereby reducing the energy loss at the interface; The P3HT/PVK interpenetrating structure bridges a transport channel, thus decreasing the carrier loss at the interface. The simultaneous mitigation of energy and carrier losses by P3HT/PVK heterointerface enables n-i-p geometry device a power conversion efficiency of 24.53% (certified 23.94%) and excellent stability. These findings demonstrate an ingenious strategy to optimize the performance of PSCs by heterointerface via Spinodal decomposition.

RESUMEN

N6-methyladenosine (m6A) is the most abundant dynamic and reversible internal chemical modification of RNA in eukaryotic cells and is essential in multiple pathophysiological processes. However, it has not been reported in atopic dermatitis (AD). We used Arraystar m6A-mRNA epitranscriptomic microarray to screen for differentially expressed genes and their m6A levels and m6A-related enzymes in patients with AD. We confirmed that the m6A RNA methyltransferase WTAP and 2 candidate differentially expressed genes (S100A9 and SERPINB3) were significantly upregulated in keratinocytes in public data and epidermal lesions of patients with AD. In vitro cell experiments confirmed that WTAP influenced the expression of the 2 candidate differentially expressed genes and promoted primary human epidermal keratinocyte proliferation while inhibiting human epidermal keratinocyte differentiation. Furthermore, we showed that WTAP, S100A9, and SERPINB3 expression correlated with AD severity. Our findings revealed that WTAP-mediated m6A modification promoted the expression of S100A9 and SERPINB3 to aggravate human epidermal keratinocyte proliferation and dysdifferentiation contributing to the pathophysiological development of AD.

RESUMEN

Objective: Primary blepharospasm (BSP) is a clinically heterogeneous disease that manifests not only as spasmodic closure of the eyelids but also sometimes with apraxia of eyelid opening (AEO). This cross-sectional study aimed to investigate differences in the neural mechanisms of isolated BSP and BSP-associated AEO subtypes, which may reveal the pathophysiology underlying different phenotypes. Methods: A total of 29 patients manifested as isolated BSP, 17 patients manifested as BSP associated with AEO, and 28 healthy controls underwent resting-state functional near-infrared spectroscopy (fNIRS). We assessed functional connectivity (FC) between regions of interest (ROIs) in the fronto-parietal control network (PFCN) and sensorimotor network (SMN). We also examined the relationship between altered FC and behavioral data. Results: In the FPCN, ROI- analyses showed decreased FC between the left premotor cortex and supramarginal gyrus in the BSP with AEO group compared to the isolated BSP group. In the SMN, both subgroups showed hypoconnectivity of the left premotor cortex with the right primary motor cortex, primary sensory cortex, and somatosensory association cortex. This hypoconnectivity was positively correlated with the total number of botulinum toxin A treatments, which suggests that long-term botulinum toxin A treatment may modulate motor sequence planning and coordination. Conclusion: These findings showed different connectivity alterations in neural networks associated with motor and cognitive control among different behavioral phenotypes of BSP. The identification of specific alterations in various networks that correspond to clinical heterogeneity may inform the identification of potential biomarkers for early diagnosis and personalized neuromodulation targets for treating different BSP subphenotypes.

RESUMEN

BACKGROUND: Acanthosis nigricans (AN) involves skin hyperpigmentation in body folds and creases. Obesity-associated AN (OB_AN) is the most common type of AN. The skin condition of obese patients with AN can be improved through bariatric surgery, such as laparoscopic sleeve gastrectomy (LSG), after weight loss. However, the contributing factors to the remission of AN after surgery are still not fully determined. The authors aimed to assess the metabolic and pathological factors associated with remission of AN following LSG in obese individuals. METHODS: The study included 319 obese patients who underwent LSG at our hospital. The subjects were divided into obesity (OB) only (OB, n =178) or OB with AN (OB_AN, n =141) groups. The basic clinical and metabolic indices and the dermatological features via reflectance confocal microscopy and histology were collected from patients prior to and after LSG. RESULTS: OB_AN patients had higher fasting plasma glucose, homeostatic model assessment for insulin resistance, and testosterone levels than OB patients. LSG could significantly improve the biochemical and histopathological features of OB_AN patients. The remissive rate of OB_AN patients was about 86.5% (122 out of 141) after surgery. The remission of OB_AN skin lesions was positively correlated with testosterone levels ( P <0.01). In addition, there was a significant positive correlation between changes in AN scores and epidermal thickness and skin pigmentation scores after surgery ( P <0.01). CONCLUSION: The remissive rate of OB_AN after LSG is associated with improved testosterone levels and reduced epidermal thickness and skin pigmentation levels.

Asunto(s)

Acantosis Nigricans , Laparoscopía , Obesidad Mórbida , Humanos , Obesidad Mórbida/complicaciones , Obesidad Mórbida/cirugía , Acantosis Nigricans/etiología , Acantosis Nigricans/cirugía , Estudios Prospectivos , Obesidad/complicaciones , Gastrectomía/efectos adversos , Testosterona , Índice de Masa Corporal , Resultado del Tratamiento

RESUMEN

NAC transcription factors (TFs) are one of the largest plant-specific gene families and play important roles in plant growth, development, and the biotic and abiotic stress response. Although the sequencing of Jojoba (Simmondsia chinensis) has been completed, the genome-wide identification and analysis of its NAC TFs has not been reported. In this study, a total of 57 genes were identified in Jojoba, which were divided into eight groups based on phylogenetic analysis. The genes clustered in the same groups have a similar gene structure and motif distribution. Based on the analysis of cis-elements in NAC TFs, nine cis-acting elements were identified in the promoter region that involved in light response, hormonal response, and stress response. Synteny analysis showed a greater collinearity between Jojoba and V. vinifera than Arabidopsis thaliana. The 24 genes in the Jojoba NAC TFs are derived from fragment replication, which may be the main source of NAC amplification. Gene expression analysis identified seven genes that were highly expressed in seeds. The differential expression analysis of NAC TFs in cotyledon and embryonic axis tissues showed that the expression of 10 genes was up-regulated and 1 gene was down-regulated. This study provides more information on the classification, gene structure, conserved motif, and evolution of NAC TFs in Jojoba, facilitating further exploration of their specific functional analysis in Jojoba seed development.

RESUMEN

Immunoglobulin A nephropathy (IgAN) is the most common type of glomerulonephritis in adults worldwide. Environmental metal exposure has been reported to be involved in the pathogenic mechanisms of kidney diseases, yet no further epidemiological study has been conducted to assess the effects of metal mixture exposure on IgAN risk. In this study, we conducted a matched case‒control design with three controls for each patient to investigate the association between metal mixture exposure and IgAN risk. A total of 160 IgAN patients and 480 healthy controls were matched for age and sex. Plasma levels of arsenic, lead, chromium, manganese, cobalt, copper, zinc, and vanadium were measured using inductively coupled plasma mass spectrometry. We used a conditional logistic regression model to assess the association between individual metals and IgAN risk, and a weighted quantile sum (WQS) regression model to analyze the effects of metal mixtures on IgAN risk. Restricted cubic splines were used to evaluate overall associations between plasma metal concentrations and estimated glomerular filtration rate (eGFR) levels. We observed that except for Cu, all the metals analyzed were nonlinearly associated with decreased eGFR, and higher concentrations of arsenic and lead were associated with elevated IgAN risk in both single-metal [3.29 (1.94, 5.57), 6.10 (3.39, 11.0), respectively] and multiple-metal [3.04 (1.66, 5.57), 4.70 (2.47, 8.97), respectively] models. Elevated manganese [1.76 (1.09, 2.83)] levels were associated with increased IgAN risk in the single-metal model. Copper was inversely related to IgAN risk in both single-metal [0.392 (0.238, 0.645)] and multiple-metal [0.357 (0.200, 0.638)] models. The WQS indices in both positive [2.04 (1.68, 2.47)] and negative [0.717 (0.603, 0.852)] directions were associated with IgAN risk. Lead, arsenic, and vanadium contributed significant weights (0.594, 0.195, and 0.191, respectively) in the positive direction; copper, cobalt, and chromium carried significant weights (0.538, 0.253, and 0.209, respectively). In conclusion, metal exposure was related to IgAN risk. Lead, arsenic, and copper were all significantly weighted factors of IgAN development, which may require further investigation.

Asunto(s)

Exposición a Riesgos Ambientales , Contaminación Ambiental , Glomerulonefritis por IGA , Metales , Adulto , Humanos , Arsénico/metabolismo , Arsénico/toxicidad , Cromo/metabolismo , Cromo/toxicidad , Cobalto/metabolismo , Cobalto/toxicidad , Cobre/metabolismo , Cobre/toxicidad , Exposición a Riesgos Ambientales/estadística & datos numéricos , Contaminantes Ambientales/metabolismo , Contaminantes Ambientales/toxicidad , Contaminación Ambiental/estadística & datos numéricos , Glomerulonefritis por IGA/inducido químicamente , Manganeso/metabolismo , Manganeso/toxicidad , Metales/metabolismo , Metales/toxicidad , Vanadio/metabolismo , Vanadio/toxicidad , Masculino , Femenino

RESUMEN

OBJECTIVES: Ozone is widely applied to treat allergic skin diseases such as eczema, atopic dermatitis, and contact dermatitis. However, the specific mechanism remains unclear. This study aims to investigate the effects of ozonated oil on treating 2,4-dinitrochlorobenzene (DNCB)-induced allergic contact dermatitis (ACD) and the underling mechanisms. METHODS: Besides the blank control (Ctrl) group, all other mice were treated with DNCB to establish an ACD-like mouse model and were randomized into following groups: a model group, a basal oil group, an ozonated oil group, a FcεRI-overexpressed plasmid (FcεRI-OE) group, and a FcεRI empty plasmid (FcεRI-NC) group. The basal oil group and the ozonated oil group were treated with basal oil and ozonated oil, respectively. The FcεRI-OE group and the FcεRI-NC group were intradermally injected 25 µg FcεRI overexpression plasmid and 25 µg FcεRI empty plasmid when treating with ozonated oil, respectively. We recorded skin lesions daily and used reflectance confocal microscope (RCM) to evaluate thickness and inflammatory changes of skin lesions. Hematoxylin-eosin (HE) staining, real-time PCR, RNA-sequencing (RNA-seq), and immunohistochemistry were performed to detct and analyze the skin lesions. RESULTS: Ozonated oil significantly alleviated DNCB-induced ACD-like dermatitis and reduced the expressions of IFN-γ, IL-17A, IL-1ß, TNF-α, and other related inflammatory factors (all P<0.05). RNA-seq analysis revealed that ozonated oil significantly inhibited the activation of the DNCB-induced FcεRI/Syk signaling pathway, confirmed by real-time PCR and immunohistochemistry (all P<0.05). Compared with the ozonated oil group and the FcεRI-NC group, the mRNA expression levels of IFN-γ, IL-17A, IL-1ß, IL-6, TNF-α, and other inflammatory genes in the FcεRI-OE group were significantly increased (all P<0.05), and the mRNA and protein expression levels of FcεRI and Syk were significantly elevated in the FcεRI-OE group as well (all P<0.05). CONCLUSIONS: Ozonated oil significantly improves ACD-like dermatitis and alleviated DNCB-induced ACD-like dermatitis via inhibiting the FcεRI/Syk signaling pathway.

Asunto(s)

Dermatitis Alérgica por Contacto , Dermatitis Atópica , Animales , Ratones , Dinitroclorobenceno/toxicidad , Dinitroclorobenceno/metabolismo , Piel/metabolismo , Citocinas/metabolismo , Interleucina-17/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Dermatitis Alérgica por Contacto/tratamiento farmacológico , Dermatitis Alérgica por Contacto/metabolismo , Dermatitis Alérgica por Contacto/patología , Dermatitis Atópica/inducido químicamente , Transducción de Señal , ARN Mensajero/metabolismo , Ratones Endogámicos BALB C

RESUMEN

The pivotal regulatory role of circular RNAs (circRNAs) in ischemic stroke (IS) has been expounded. The study aimed to probe the exact role and underlying mechanism of circVRK1 in oxygen-glucose deprivation (OGD)-induced human brain microvascular endothelial cells (HBMECs) injury. HBMECs challenged by OGD were used as in vitro models of IS. Quantitative real-time PCR was used to examine the levels of circVRK1, vaccinia-related kinase 1 (VRK1), miR-150-5p and MLLT1 mRNA. Cell viability, migration angiogenesis ability and death were evaluated by Cell counting kit-8 assay, transwell assay, wound-healing assay, tube formation assay and flow cytometry analysis. All the protein levels were monitored by western blot assay. Enzyme-linked immunosorbent assay was conducted for examining cell oxidative stress. Dual-luciferase reporter assay, RIP assay and RNA pull-down assay were performed to verify the combination between miR-150-5p and circVRK1 or MLLT1. CircVRK1 was upregulated in OGD-treated HBMECs. CircVRK1 knockdown alleviated OGD-caused effects on HBMECs migration, angiogenesis, death, inflammatory response and oxidative stress. Furthermore, circVRK1 could sponge miR-150-5p, and miR-150-5p silencing also mitigated the impact of circVRK1 deficiency on OGD-evoked injury. Besides, MLLT1 acted as a molecular target of miR-150-5p, and the protective influence of miR-150-5p on OGD-induced cell damage was overturned by MLLT1 introduction. CircVRK1 knockdown weakened OGD-evoked injury in HBMECs through modulating miR-150-5p/MLLT1 pathway, and this might supply new insights and probable targets for IS treatment.

Asunto(s)

Lesiones Encefálicas , MicroARNs , Humanos , Células Endoteliales , Regulación hacia Abajo , Encéfalo , Proteínas de Neoplasias , Proteínas Nucleares , Factores de Transcripción , Proteínas Serina-Treonina Quinasas , Péptidos y Proteínas de Señalización Intracelular