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RATIONALE: Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy is a rare autoimmune disease of the central nervous system that affects the meninges, brain, spinal cord, and optic nerves. GFAP astrocytopathy can coexist with a variety of antibodies, which is known as overlap syndrome. Anti-NMDAR-positive encephalitis overlap syndrome has been reported; however, encephalitis overlap syndrome with both anti-NMDAR and sulfatide-IgG positivity has not been reported. PATIENT CONCERNS: The patient was a 50-year-old male who was drowsy and had chills and weak limbs for 6 months. His symptoms worsened after admission to our hospital with persistent high fever, dysphoria, gibberish, and disturbance of consciousness. Positive cerebrospinal fluid NMDA, GFAP antibodies, and serum sulfatide antibody IgG were positive. DIAGNOSES: Autoimmune GFAP astrocytopathy with anti-NMDAR and sulfatide-IgG-positive encephalitis overlap syndrome. INTERVENTIONS: In addition to ventilator support and symptomatic supportive treatment, step-down therapy with methylprednisolone (1000 mg/d, halved every 3 days) and pulse therapy with human immunoglobulin (0.4 g/(kg d) for 5 days) were used. OUTCOMES: After 6 days of treatment, the patient condition did not improve, and the family signed up to give up the treatment and left the hospital. CONCLUSIONS: Patients with autoimmune GFAP astrocytopathy may be positive for anti-NMDAR and sulfatide-IgG, and immunotherapy may be effective in patients with severe conditions. LESSONS: Autoimmune GFAP astrocytopathy with nonspecific symptoms is rarely reported and is easy to be missed and misdiagnosed. GFAP astrocytopathy should be considered in patients with fever, headache, disturbance of consciousness, convulsions, and central infections that do not respond to antibacterial and viral agents. Autoimmune encephalopathy-related antibody testing should be performed as soon as possible, early diagnosis should be confirmed, and immunomodulatory therapy should be administered promptly.
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Proteína Ácida Fibrilar de la Glía , Sulfoglicoesfingolípidos , Humanos , Masculino , Persona de Mediana Edad , Proteína Ácida Fibrilar de la Glía/inmunología , Proteína Ácida Fibrilar de la Glía/sangre , Sulfoglicoesfingolípidos/inmunología , Inmunoglobulina G/sangre , Inmunoglobulina G/líquido cefalorraquídeo , Autoanticuerpos/sangre , Metilprednisolona/uso terapéutico , Encefalitis/diagnóstico , Encefalitis/inmunología , Encefalitis Antirreceptor N-Metil-D-Aspartato/diagnóstico , Encefalitis Antirreceptor N-Metil-D-Aspartato/inmunología , Encefalitis Antirreceptor N-Metil-D-Aspartato/complicaciones , Astrocitos/inmunología , Astrocitos/patología , Enfermedades Autoinmunes del Sistema Nervioso/diagnóstico , Enfermedades Autoinmunes del Sistema Nervioso/inmunologíaRESUMEN
BACKGROUND: Alcohol-associated liver disease (ALD) is a prevalent liver ailment. It has escalated into a significant public health issue, imposing substantial burdens on medical, economic, and social domains. Currently, oxidative stress, inflammation, and apoptosis are recognized as crucial culprits in improving ALD. Consequently, mitigating these issues has emerged as a promising avenue for enhancing ALD. Hydroxysafflor yellow A (HSYA) is the main ingredient in safflower, showing excellent antioxidative stress, anti-inflammatory, and anti-apoptosis traits. However, there are limited investigations into the mechanisms by which HSYA ameliorates ALD PURPOSE: We investigated whether HSYA, a significant constituent of Asteraceae safflower, exerts antioxidant stress and attenuates inflammation and anti-apoptotic effects through PI3K/Akt and STAT3/NF-κB pathways, thereby ameliorating ALD METHODS: We established two experimental models: an ethanol-induced liver damage mouse model in vivo and a HepG2 cell alcohol injury model in vitro RESULTS: The results demonstrated that HSYA effectively ameliorated liver tissue damage, reduced levels of ALT, AST, LDL-C, TG, TC, and MDA, enhanced HDL-C levels, SOD and GSH activities, reduced ROS accumulation in cells, and activated the Nrf2 pathway, a transcription factor involved in antioxidant defense. By regulating the PI3K/Akt and STAT3/NF-κB pathways, HSYA exhibits notable antioxidative stress, anti-inflammatory, and anti-apoptotic effects, effectively impeding ALD's advancement. To further confirm the regulatory effect of HSYA on PI3K/Akt and downstream signaling pathways, the PI3K activator 740 Y-P was used and was found to reverse the downregulation of PI3K by HSYA CONCLUSION: This study supports the effectiveness of HSYA in reducing ALD by regulating the PI3K/Akt and STAT3/NF-κB pathways, indicating its potential medicinal value.
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Chalcona , FN-kappa B , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Quinonas , Factor de Transcripción STAT3 , Transducción de Señal , Chalcona/farmacología , Chalcona/análogos & derivados , Animales , Factor de Transcripción STAT3/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal/efectos de los fármacos , Quinonas/farmacología , FN-kappa B/metabolismo , Humanos , Fosfatidilinositol 3-Quinasas/metabolismo , Masculino , Células Hep G2 , Ratones , Estrés Oxidativo/efectos de los fármacos , Antioxidantes/farmacología , Etanol , Hepatopatías Alcohólicas/tratamiento farmacológico , Ratones Endogámicos C57BL , Apoptosis/efectos de los fármacos , Modelos Animales de Enfermedad , Hígado/efectos de los fármacosRESUMEN
Rheumatoid arthritis (RA) and primary Sjögren's syndrome (pSS) are the most common systemic autoimmune diseases, and they are increasingly being recognized as occurring in the same patient population. These two diseases share several clinical features and laboratory parameters, but the exact mechanism of their co-pathogenesis remains unclear. The intention of this study was to investigate the common molecular mechanisms involved in RA and pSS using integrated bioinformatic analysis. RNA-seq data for RA and pSS were picked up from the Gene Expression Omnibus (GEO) database. Co-expression genes linked with RA and pSS were recognized using weighted gene co-expression network analysis (WGCNA) and differentially expressed gene (DEG) analysis. Then, we screened two public disease-gene interaction databases (GeneCards and Comparative Toxicogenomics Database) for common targets associated with RA and pSS. The DGIdb database was used to predict therapeutic drugs for RA and pSS. The Human microRNA Disease Database (HMDD) was used to screen out the common microRNAs associated with RA and pSS. Finally, a common miRNA-gene network was created using Cytoscape. Four hub genes (CXCL10, GZMA, ITGA4, and PSMB9) were obtained from the intersection of common genes from WGCNA, differential gene analysis and public databases. Twenty-four drugs corresponding to hub gene targets were predicted in the DGIdb database. Among the 24 drugs, five drugs had already been reported for the treatment of RA and pSS. Other drugs, such as bortezomib, carfilzomib, oprozomib, cyclosporine and zidovudine, may be ideal drugs for the future treatment of RA patients with pSS. According to the miRNA-gene network, hsa-mir-21 may play a significant role in the mechanisms shared by RA and pSS. In conclusion, we identified commom targets as potential biomarkers in RA and pSS from publicly available databases and predicted potential drugs based on the targets. A new understanding of the molecular mechanisms associated with RA and pSS is provided according to the miRNA-gene network.
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Artritis Reumatoide , MicroARNs , Síndrome de Sjögren , Humanos , Síndrome de Sjögren/tratamiento farmacológico , Síndrome de Sjögren/genética , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/genética , MicroARNs/genética , Perfilación de la Expresión Génica , Redes Reguladoras de GenesRESUMEN
RATIONALE: Coronavirus disease 2019 (COVID-19) can damage the central nervous system. Although there have been reports of cerebral hemorrhage and infarction caused by COVID-19, hematomyelia due to COVID-19 has never been reported. PATIENT CONCERNS: A 40-year-old male was admitted to the hospital with positive nucleic acid detection for COVID-19 after experiencing fever for 2 weeks, urinary retention, fecal retention, and pain in both lower extremities for a week. DIAGNOSES: The patient diagnosis was established using thoracic and lumbar magnetic resonance imaging (MRI). Contrast-enhanced thoracic and lumbar MRI revealed subdural (dorsal predominant) short T1 and slightly long T2 bands in the T12-S2 infundibular canal in the scan field, and the subdural hematoma was yet to be distinguished from other diseases. Spinal cord edema was observed in the left vertebral plate and facet joint of the T11 vertebral body, indicative of inflammation. The cerebrospinal fluid (CSF) was positive for COVID-19 nucleic acid. INTERVENTIONS: Antiinfection, immunomodulation, correction of acid-base balance and electrolyte disorders, improvement of circulation, nerve nutrition, and other symptomatic supportive treatments were administered to the patient. OUTCOMES: The patient symptoms significantly improved after 4 weeks of anti-infection and immunomodulatory therapy. Repeat thoracolumbar MRI revealed absorption of the spinal cord hematoma, and the patient was discharged from the hospital. To date, COVID-19-related hematomyelia has not been reported and anti-infective and immunomodulatory therapies may be effective. LESSONS: COVID-19 not only easily leads to brain injury but can also cause spinal cord injury and even spinal cord hemorrhage. When patients with COVID-19 experience symptoms and signs of spinal cord injury, spinal cord injury and bleeding caused by COVID-19 should be considered, and MRI and lumbar puncture should be performed as soon as possible to make a clear diagnosis.
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COVID-19 , Enfermedades de la Médula Espinal , Traumatismos de la Médula Espinal , Enfermedades Vasculares de la Médula Espinal , Masculino , Humanos , Adulto , COVID-19/complicaciones , Columna Vertebral/patología , Hematoma/patología , Imagen por Resonancia MagnéticaRESUMEN
BACKGROUND: Cholestasis is a commonly occurring disorder induced by impaired bile flow, for which there is no effective treatment so far. Qingre Lidan decoction (QRLD) is a clinically used herbal compound for the long-term treatment of bile circulation disorders arising from inflammation and obstruction in the gallbladder and bile ducts. The objective of this study was to investigate the protective effect of QRLD on cholestatic liver injury and its possible mechanism. METHODS: α-Naphthyl isothiocyanate (ANIT) was used to induce cholestatic liver injury in rats. Liver histopathology and serum biochemical markers were used to assess QRLD's protective impact. The possible biomarkers and mechanism of the therapeutic benefits of QRLD were investigated using a UHPLC-based Q-Exactive Orbitrap MS / MS untargeted serum metabolomics technique together with 16 S rRNA microbiota profiling. Afterwards, using RT-qPCR as well as Western Blot techniques, the expression of pertinent indicators was determined. RESULTS: The intervention effect of QRLD was stronger at medium and high dosages than at low doses, and it dramatically decreased the levels of serum biochemical markers in cholestatic rats reflecting alterations in liver function and relieving ANIT-induced abnormalities in the liver's histopathology. Serum metabolomics showed that QRLD could affect the metabolic profile of cholestatic rats, mainly related to glycerophospholipid metabolism, taurine and hypotaurine metabolism, alanine, aspartate and glutamate metabolism, and histidine metabolic pathway. Additionally, analysis of 16 S rRNA gene sequencing indicated that QRLD could moderate ANIT-induced microbiota disorders, particularly Romboutsia, Bifidobacterium, Fusicatenibacter, Prevotella_9, Prevotellaceae_NK3B31_group and Prevotella_1. Other experimental results showed that QRLD significantly upregulated the mRNA and protein expression of PPARα, CYP7A1 and NTCP in the liver, inhibited the expression of p-IκBα, p-p65 and TNFα while increasing the anti-inflammatory factor IL-10, and downregulated the expression of MDA (a peroxidation product) and D-lactic acid (an intestinal barrier indicator) while increasing the expression of SOD and GSH. CONCLUSIONS: QRLD can effectively regulate endogenous metabolites and microbiota disorders in cholestatic rats that are correlated with the attenuation of inflammation and oxidative stress.
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Colestasis , Hígado , Ratas , Animales , Genes de ARNr , Hígado/metabolismo , Colestasis/tratamiento farmacológico , Colestasis/genética , Colestasis/metabolismo , Metabolómica , Inflamación/patología , Biomarcadores/metabolismoRESUMEN
We report an experimental study of the spin-orbit interaction (SOI) in an epitaxially grown free-standing InAs nanosheet in a dual-gate field-effect device. Gate-transfer characteristic measurements show that independent tuning of the carrier density in the nanosheet and the potential difference across the nanosheet can be efficiently achieved with the use of a dual gate. The quantum transport characteristics of the InAs nanosheet are investigated by magnetoconductance measurements at low temperatures. It is shown that the electron transport in the nanosheet can be tuned from the weak antilocalization to the weak localization and then back to the weak antilocalization regime with a voltage applied over the dual gate without a change in the carrier density. The spin-orbit length extracted from the magnetoconductance measurements at a constant carrier density exhibits a peak value at which the SOI of the Rashba type is suppressed and the spin relaxation due to the presence of an SOI of the Dresselhaus type in the nanosheet can be revealed. Energy band diagram simulations have also been carried out for the device under the experimental conditions and the physical insights into the experimental observations have been discussed in light of the results of simulations.
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Long noncoding RNAs (LncRNAs) are reported to exhibit crucial roles in cancer progression. LINC00707 is recently indicated to be a significant oncogene in various cancers. Up to now, the mechanism of LINC00707 in cervical cancer is still unclear. In this study, our present work was designed to study the biological effects of LINC00707 in cervical cancer. Firstly, the expression level of LINC00707 in cervical cancer was tested. We observed LINC00707 expression was greatly increased in cervical cancer. Then, we assessed the detailed effect of LINC00707 on the development of cervical cancer using CCK-8 assay, Transwell assays, and tumor xenograft experiments. Gain-of-function and loss-of-function assays revealed the function of LINC00707 in cervical cancer progression. In addition, the action of LINC00707 in cervical cancer cells was studied using bioinformatic tools and luciferase reporter experiment. It was displayed that loss of LINC00707 significantly repressed cell growth of cervical cancer. Meanwhile, restoration of LINC00707 expression obviously induced cervical cancer cell growth. Then, we predicted that LINC00707 could serve as a molecular sponge for miR-382-5p to modulate VEGFA expression in cervical cancer. Subsequently, lack of VEGFA expression reversed the influence of miR-382-5p knockdown on cervical cancer cells. In conclusion, our findings evidenced the significant role of LINC00707-miR-382-5p-VEGFA network in cervical cancer and it can provide an attractive target.
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Regulación Neoplásica de la Expresión Génica , MicroARNs/metabolismo , ARN Largo no Codificante/metabolismo , Neoplasias del Cuello Uterino/genética , Factor A de Crecimiento Endotelial Vascular/genética , Animales , Línea Celular Tumoral , Movimiento Celular/genética , Progresión de la Enfermedad , Femenino , Técnicas de Silenciamiento del Gen , Humanos , Ratones , MicroARNs/genética , Organismos Libres de Patógenos Específicos , Neoplasias del Cuello Uterino/patología , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Low-dimensional narrow-band-gap III-V semiconductors are key building blocks for the next generation of high-performance nanoelectronics, nanophotonics, and quantum devices. Realizing these various applications requires an efficient methodology that enables the material dimensional control during the synthesis process and the mass production of these materials with perfect crystallinity, reproducibility, low cost, and outstanding electronic and optoelectronic properties. Although advances in one- and two-dimensional narrow-band-gap III-V semiconductors synthesis, the progress toward reliable methods that can satisfy all of these requirements has been limited. Here, we demonstrate an approach that provides a precise control of the dimension of InAs from one-dimensional nanowires to wafer-scale free-standing two-dimensional nanosheets, which have a high degree of crystallinity and outstanding electrical and optical properties, using molecular-beam epitaxy by controlling catalyst alloy segregation. In our approach, two-dimensional InAs nanosheets can be obtained directly from one-dimensional InAs nanowires by silver-indium alloy segregation, which is much easier than the previously reported methods, such as the traditional buffering technique and select-area epitaxial growth. Detailed transmission electron microscopy investigations provide solid evidence that the catalyst alloy segregation is the origination of the InAs dimensional transformation from one-dimensional nanowires to two-dimensional nanosheets and even to three-dimensional complex crosses. Using this method, we find that the wafer-scale free-standing InAs nanosheets can be grown on various substrates including Si, MgO, sapphire, GaAs, etc. The InAs nanosheets grown at high temperature are pure-phase single crystals and have a high electron mobility and a long time-resolved terahertz kinetics lifetime. Our work will open up a conceptually new and general technology route toward the effective controlling of the dimension of the low-dimensional III-V semiconductors. It may also enable the low-cost fabrication of free-standing nanosheet-based devices on an industrial scale.
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Co-culture methods are widely used in tissue engineering to drive tissue formation with the direct or indirect interaction of multiple cell types. Klotho is a novel biomarker involved in aging. In this study, we evaluated the protective effects of klotho overexpressed adipose-derived stem cells (ADSCs) against ultraviolet radiation B (UVB)-induced photoaging in co-cultured human skin fibroblasts (HSF2 cell line). Furthermore, the involvement of P38 mitogen-activated protein kinase (MAPK) signaling was investigated. ADSCs were isolated from human subcutaneous adipose tissue and the 3rd generation of ADSCs was used after being identified. Klotho overexpression (OE) lentivirus vectors were constructed and identified in ADSCs. The HSF2 cells were seeded in the upper layer of the Transwell co-culture plate (0.4 µm pore polycarbonate membrane) and ADSCs were seeded in the lower layer. UVB irradiation of HSF2 cells was performed using UVB lamps in uncovered petri dishes at room temperature. The present results indicated that the proliferation of ADSCs was increased by klotho OE. Furthermore the proliferation and collagen content of HSF2 were decreased by UVB irradiation in a dose-dependent manner. By contrast, the protein level of matrix metalloproteinases (MMP) 1, 3 and p-P38 in HSF2 were upregulated. In the co-culture system, relative mRNA expression of MMP-1 and MMP-3 as well as protein level of MMP-1, MMP-3 and p-P38 in HSF2 were reduced by co-culture with klotho overexpressed ADSCs when exposed to UVB (20 mJ/cm2). By contrast, the collagen content of HSF2 was increased. Collectively, OE of klotho in ADSCs notably ameliorates UVB-induced photoaging in co-cultured HSF2, and these effects were potentially achieved by increasing the collagen content and decreasing the protein level of MMP-1, MMP-3 and p-P38.