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CONTEXT: Many studies have explored new methods to cure acute lung injury (ALI); however, none of those methods could significantly change the high mortality rate of ALI. Shenfu is a Chinese traditional medicine that might be effective against ALI. OBJECTIVE: Our study explores the therapeutic potential of Shenfu in ALI. MATERIALS AND METHODS: Male C57BL/6 mice were assigned to control, lipopolysaccharide (LPS) (500 µg/100 µL per mouse), and LPS + Shenfu (30 mL/kg) groups. Shenfu (10 µL/mL) was added to LPS (10 µg/mL) treated MLE-12 cells for 48 h in vitro. Male C57BL/6 mice were divided into four groups: LPS, LPS + 3% dextran sulphate sodium (DSS), 3% DSS + Shenfu, and LPS + 3% DSS + Shenfu. RESULTS: Compared with the ALI group, Shenfu reduced wet/dry weight ratio (19.8%, 36.2%), and reduced the IL-2 (40.9%, 61.6%), IFN-γ (43.5%, 53.3%) TNF-α (54.1%, 42.1%), IL-6 (54.8%,70%), and IL-1ß (39.9%, 65.1%), reduced serum uric acid (18.8%, 48.7%) and creatinine (17.4%, 41.1%). Moreover, Shenfu enhanced cell viability (17.2%, 59.9%) and inhibited cell apoptosis (63.0%) and p38/ERK phosphorylation in in vitro cultured epithelial cells with LPS stimulation. Mechanistically, Shenfu mediated the protective effect by upregulating claudin-4 expression. In addition, Shenfu could protect against both lung and intestinal epithelial damage in acute gastrointestinal injury-exacerbated ALI. DISCUSSION AND CONCLUSIONS: Taken together, the results revealed the therapeutic effect and the underlying mechanism of Shenfu injection in an ALI in mouse model, indicating its clinical potential to treat patients with ALI.
Assuntos
Lesão Pulmonar Aguda , Lipopolissacarídeos , Lesão Pulmonar Aguda/tratamento farmacológico , Animais , Claudina-4/metabolismo , Creatinina , Sulfato de Dextrana , Medicamentos de Ervas Chinesas , Interleucina-2/metabolismo , Interleucina-6/metabolismo , Lipopolissacarídeos/toxicidade , Pulmão , Masculino , Medicina Tradicional Chinesa , Camundongos , Camundongos Endogâmicos C57BL , Fator de Necrose Tumoral alfa/metabolismo , Regulação para Cima , Ácido ÚricoRESUMO
The N-methyl-d-aspartate (NMDA) receptor, a typical ionotropic glutamate receptor, is a crucial protein for maintaining brain function. GluN2A and GluN2B are the main types of NMDA receptor subunit in the adult forebrain. Studies have demonstrated that they play different roles in a number of pathophysiological processes. Although the underlying mechanism for this has not been clarified, the most fundamental reason may be the differences between the signaling pathways associated with GluN2A and GluN2B. With the aim of elucidating the reasons behind the diverse roles of these two subunits, we described the signaling differences between GluN2A and GluN2B from the aspects of C-terminus-associated molecules, effects on typical downstream signaling proteins, and metabotropic signaling. Because there are several factors interfering with the determination of subunit-specific signaling, there is still a long way to go toward clarifying the signaling differences between these two subunits. Developing better pharmacology tools, such as highly selective antagonists for triheteromeric GluN2A- and GluN2B-containing NMDA receptors, and establishing new molecular biological methods, for example, engineering photoswitchable NMDA receptors, may be useful for clarifying the signaling differences between GluN2A and GluN2B.
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Encéfalo/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Animais , Antagonistas de Aminoácidos Excitatórios/farmacologia , Ácido Glutâmico/metabolismo , Neurônios/metabolismo , Técnicas de Patch-Clamp , Transdução de SinaisRESUMO
An increasing number of cases have reported that coronavirus disease 2019 (COVID-19) can lead to immune system dysregulation and induce autoimmune diseases, but the mechanism is unclear. We treated a patient who presented with an unknown fever after infection with the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 2023. After excluding the possibility of infection, malignancy, and other connective tissue diseases, we considered the diagnosis of IgG4-related disease in consideration of the patient's pathology and clinical findings. In this article, we summarize our diagnostic experience and summarize the case reports of IgG4-related diseases associated with SARS-CoV-2 infections since the COVID-19 pandemic.
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COVID-19 , Doenças do Tecido Conjuntivo , Doença Relacionada a Imunoglobulina G4 , Humanos , COVID-19/complicações , COVID-19/diagnóstico , SARS-CoV-2 , Pandemias , Imunoglobulina G , Doença Relacionada a Imunoglobulina G4/diagnóstico , Doença Relacionada a Imunoglobulina G4/tratamento farmacológicoRESUMO
Mesenchymal stem cell-derived exosomes and long non-coding RNAs (lncRNAs) have been identified to play a role in acute lung injury (ALI). In this study, we investigated whether exosomal lncRNAs could regulate ALI and the underlying mechanisms. Bone marrow mesenchymal stem cells (BM-MSCs) were pretreated with hypoxia or normoxia, and exosomes were subsequently extracted from normoxic BM-MSCs (Nor-exos) and hypoxic BM-MSCs (Hypo-exos). A rat model of ALI was established via an airway perfusion of lipopolysaccharide (LPS). Exosomes were administered via the tail vein to evaluate the in vivo effect of exosomes in ALI. LPS-exposed RLE-6TN cells were incubated with exosomes to explore their in vitro effect in ALI. A luciferase reporter assay was used to evaluate the interaction between lncRNA XIST and miR-455-3p, as well as miR-455-3p and Claudin-4. We found that the exosomes attenuated LPS-induced ALI and Hypo-Exos exerted a greater therapeutic effect compared with Nor-exos both in vitro and in vivo. Moreover, an abundance of lncRNA XIST was observed in Hypo-exos compared with Nor-exos. Mechanistically, LncRNA XIST functioned as a miR-455-3p sponge and targeted Claudin-4 in ALI. Our results provide novel insight into the role of exosomal lncRNA XIST for the treatment of ALI. Thus, hypoxic pretreatment may represent an effective method for improving the therapeutic effects of exosomes.
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Lesão Pulmonar Aguda , Células-Tronco Mesenquimais , MicroRNAs , RNA Longo não Codificante , Animais , Ratos , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/terapia , Lesão Pulmonar Aguda/genética , Claudina-4 , Hipóxia , Lipopolissacarídeos , MicroRNAs/genética , RNA Longo não Codificante/genéticaRESUMO
Metal sulfide is the most promising anode material for sodium storage devices due to its high theoretical capacity and low cost. However, the practical application of metal sulfide is largely hindered by huge capacity fading during the sodiation/desodiation process. Here mixed bimetallic sulfides grown on reduced graphene oxide (MoS2/CoS2-RGO) are prepared via a facile hydrothermal method. MoS2/CoS2-RGO displays a unique 2D structure which provides large specific surface area for pseudocapacitive charge storage, polyvalent ion reaction for ultrahigh capacity, and a heterostructure to high Na-ion diffusion rate. The optimized MoS2/CoS2-RGO shows a considerable reversible capacity of 593.6 mA h g-1 at 100 mA g-1 over 50 cycles and a high rate capability of 215.8 mA h g-1 even at a high specific current of 5000 mA g-1. A reaction kinetics and galvanostatic intermittent titration technique analysis indicates that MoS2/CoS2-RGO possesses fast pseudocapacitive charge storage and high Na-ion diffusion rate, benefiting the kinetics balance between anode and cathode. With this special structure, SICs containing the anode deliver a high specific energy of 152.98 W h kg-1 at 562.5 W kg-1. Similarly, the SIB exhibits a good capacities of 64 mA h g-1 at the high rates of 5C over 100 cycles.
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Tripterygium wilfordii Hook F has significant anti-inflammatory and immunosuppressive properties and is widely used for treating autoimmune and inflammatory diseases such as rheumatoid arthritis, systemic lupus erythematosus, and kidney disease, especially in traditional Chinese medicine. The mechanisms underlying its effects may be diverse but they remain unclear, and its toxicity and side effects limit its wider clinical application. This review summarizes the clinical application of Tripterygium wilfordii Hook F in recent years, as well as the results of studies into its mechanisms and toxicity, to provide a reference for its future clinical application.
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Medicamentos de Ervas Chinesas/uso terapêutico , Inflamação/tratamento farmacológico , Medicina Tradicional Chinesa , Tripterygium , Animais , Anti-Inflamatórios/farmacologia , Artrite Reumatoide/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Imunossupressores/farmacologia , Doenças Inflamatórias Intestinais/tratamento farmacológico , Piroptose/efeitos dos fármacosRESUMO
OBJECTIVE: To provide comprehensive data to understand mechanisms of vascular endothelial cell (VEC) response to hypoxia/re-oxygenation. METHODS: Human umbilical vein endothelial cells (HUVECs) were employed to construct hypoxia/re-oxygenation-induced VEC transcriptome profiling. Cells incubated under 5% O2, 5% CO2, and 90% N2 for 3 h followed by 95% air and 5% CO2 for 1 h were used in the hypoxia/re-oxygenation group. Those incubated only under 95% air and 5% CO2 were used in the normoxia control group. RESULTS: By using a well-established microarray chip consisting of 58 339 probes, the study identified 372 differentially expressed genes. While part of the genes are known to be VEC hypoxia/re-oxygenation-related, serving as a good control, a large number of genes related to VEC hypoxia/re-oxygenation were identified for the first time. Through bioinformatic analysis of these genes, we identified that multiple pathways were involved in the reaction. Subsequently, we applied real-time polymerase chain reaction (PCR) and western blot techniques to validate the microarray data. It was found that the expression of apoptosis-related proteins, like pleckstrin homology-like domain family A member 1 (PHLDA1), was also consistently up-regulated in the hypoxia/re-oxygenation group. STRING analysis found that significantly differentially expressed genes SLC38A3, SLC5A5, Lnc-SLC36A4-1, and Lnc-PLEKHJ1-1 may have physical or/and functional protein-protein interactions with PHLDA1. CONCLUSIONS: The data from this study have built a foundation to develop many hypotheses to further explore the hypoxia/re-oxygenation mechanisms, an area with great clinical significance for multiple diseases.
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Hipóxia Celular , Células Endoteliais da Veia Umbilical Humana/metabolismo , Análise em Microsséries/métodos , Transcriptoma , Células Cultivadas , Biologia Computacional , Humanos , Fatores de Transcrição/genéticaRESUMO
Background: Myeloid derived suppressor cells (MDSCs) have been reported to keep elevating during sepsis. The current study was performed to investigate the immunosuppressive effect of MDSCs and their subsets with the underlying mechanisms. Methods: The immunosuppressive status was manifested by the apoptosis of splenocytes, quantity of T cells and PD-1 expression. The dynamics of quantity and PD-L1 level of MDSCs and the subsets were determined over time. The subset of MDSCs with high PD-L1 level was co-cultured with T cells to observe the suppressive effect. Results: Abdominal abscess was observed after 7 days post-sepsis. Five biomarkers related to organ functions were all significantly higher in the CLP group. The survival rate was consistent with the middle grade severity of sepsis model. Apoptosis of splenocytes increased over time during sepsis; CD4 + T cell decreased from day 1 post-sepsis; CD8+ T cells significantly reduced at day 7. The PD-1 expression in spleen was upregulated from an early stage of sepsis, and negatively related with the quantity of T cells. MDSCs were low at day 1 post-sepsis, but increased to a high level later; the dynamics of PMN-MDSC was similar to MDSCs. PD-L1 on MDSCs was highest at day 1 post-sepsis; PMN-MDSC was the main subset expressing PD-L1. The PMN-MDSC with high PD-L1 expression level extracted on day 1 after surgery from CLP mice significantly inhibited the proliferation of T cells. Conclusions: Sepsis-induced immunosuppression is initiated from a very early stage, a high expression level of PD-L1 on MDSCs and the main subset, PMN-MDSC might play a critical role suppressive role on T cells through PD-L1/PD-1 axis.
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Antígeno B7-H1/metabolismo , Imunomodulação , Células Supressoras Mieloides/imunologia , Células Supressoras Mieloides/metabolismo , Receptor de Morte Celular Programada 1/metabolismo , Sepse/etiologia , Sepse/metabolismo , Animais , Apoptose/genética , Apoptose/imunologia , Biomarcadores , Modelos Animais de Doenças , Progressão da Doença , Inflamação/etiologia , Inflamação/metabolismo , Inflamação/patologia , Masculino , Camundongos , Índice de Gravidade de Doença , Baço/imunologia , Baço/metabolismo , Linfócitos T/imunologia , Linfócitos T/metabolismoRESUMO
Paraquat (PQ), a highly effective herbicide, is widely used worldwide. PQ poisoning can cause multiple organ failure, in which the lung is the primary target organ. After PQ poisoning, the patient mortality rate is as high as 90%, and there is currently no specific antidote. The main clinical treatment is the use of glucocorticoids and cyclophosphamide for pulse therapy, but its effectiveness and safety are still uncertain. We investigated the effectiveness and safety of immunosuppressive pulse therapy with glucocorticoids and cyclophosphamide to evaluate the treatment value in patients with acute PQ poisoning. This meta-analysis, combined with seven trials that enrolled a total of 426 patients, showed that immunosuppressive pulse therapy with glucocorticoids and cyclophosphamide for PQ poisoning significantly reduced mortality of the study group (59.3%, 134/226) compared with the control group (81.0%, 162/200). There was no significant difference of hepatitis or renal failure between the control and study groups, indicating that immunosuppressive pulse therapy was relatively safe. Several patients were reported to have leukopenia and returned to normal after 1-2 weeks without any abnormalities. Two cases of non-fatal sepsis were reported and considered to be a side effect of the immunosuppressive pulse therapy. Thus, immunosuppressive pulse therapy can efficiently reduce the mortality of PQ poisoning and it is relatively safe.