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Parallel single-cell multimodal sequencing is the most intuitive and precise tool for cellular status research. In this study, we propose AMAR-seq to automate methylation, chromatin accessibility, and RNA expression coanalysis with single-cell precision. We validated the accuracy and robustness of AMAR-seq in comparison with standard single-omics methods. The high gene detection rate and genome coverage of AMAR-seq enabled us to establish a genome-wide gene expression regulatory atlas and triple-omics landscape with single base resolution and implement single-cell copy number variation analysis. Applying AMAR-seq to investigate the process of mouse embryonic stem cell differentiation, we revealed the dynamic coupling of the epigenome and transcriptome, which may contribute to unraveling the molecular mechanisms of early embryonic development. Collectively, we propose AMAR-seq for the in-depth and accurate establishment of single-cell multiomics regulatory patterns in a cost-effective, efficient, and automated manner, paving the way for insightful dissection of complex life processes.

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Intervertebral disc degeneration (IVDD) may lead to an increase in extracellular matrix (ECM) stiffness, contributing to the progression of the disease. Melatonin reportedly mitigates IVDD; while its potential to attenuate elevated matrix stiffness-induced IVDD remains unexplored. Therefore, we aimed to investigate whether melatonin can alleviate the progression of IVDD triggered by increased matrix stiffness and elucidate its mechanisms. Nucleus pulposus (NP) tissues were collected from patients, and ECM stiffness, reactive oxygen species (ROS) levels, apoptosis rates, and p65 expression in these tissues with varying Pfirrmann scores were determined. In vitro experiments were conducted to investigate the effects of melatonin on the NP cells cultured on soft substrate with differing stiffness levels. Our findings revealed a positive correlation between ECM stiffness in human NP tissue and degree of IVDD. Additionally, phosphorylation of P65 exhibited a strong association with matrix stiffness. Enhanced levels of ROS and cellular apoptosis were observed within degenerated intervertebral discs. In vitro experiments demonstrated that melatonin significantly inhibited catabolism and apoptosis induced by stiff matrices, along with elevated ROS levels. Furthermore, we observed that melatonin inhibited NP cell catabolism and apoptosis by reducing the melatonin receptors mediated activation of the PI3K/AKT and NF-κB pathways. Also, we found that the reduction of ROS by melatonin can assist in inhibiting the activation of the NF-κB pathway. The outcomes of the in vivo experiments corroborated the results of the in vitro experiments. Collectively, melatonin can potentially alleviate high matrix stiffness-induced IVDD by reducing intracellular ROS levels and inhibiting the PI3K/AKT/NF-κB pathway.

RESUMEN

Assessing the bioaccessibility and bioavailability of cadmium (Cd) is crucial for effective evaluation of the exposure risk associated with intake of Cd-contaminated rice. However, limited studies have investigated the influence of gut microbiota on these two significant factors. In this study, we utilized in vitro gastrointestinal simulators, specifically the RIVM-M (with human gut microbial communities) and the RIVM model (without gut microbial communities), to determine the bioaccessibility of Cd in rice. Additionally, we employed the Caco-2 cell model to assess bioavailability. Our findings provide compelling evidence that gut microbiota significantly reduces Cd bioaccessibility and bioavailability (p<0.05). Notably, strong in vivo-in vitro correlations (IVIVC) were observed between the in vitro bioaccessibilities and bioavailabilities, as compared to the results obtained from an in vivo mouse bioassay (R2 = 0.63-0.65 and 0.45-0.70, respectively). Minerals such as copper (Cu) and iron (Fe) in the food matrix were found to be negatively correlated with Cd bioaccessibility in rice. Furthermore, the results obtained from the toxicokinetic (TK) model revealed that the predicted urinary Cd levels in the Chinese population, based on dietary Cd intake adjusted by in vitro bioaccessibility from the RIVM-M model, were consistent with the actual measured levels (p > 0.05). These results indicated that the RIVM-M model represents a potent approach for measuring Cd bioaccessibility and underscore the crucial role of gut microbiota in the digestion and absorption process of Cd. The implementation of these in vitro methods holds promise for reducing uncertainties in dietary exposure assessment.

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A concise synthesis of aryl enol ethers from allylic alcohols and arylsulfonium salts by simply using an inorganic base as a mediator is described. The reaction enabled the facile conversion of various α-aryl allylic alcohols into the corresponding aryl enol ethers in good yields with excellent selectivity. The results demonstrated that both symmetric triarylsulfonium triflate and 10-methyl-5-aryl-5,10-dihydrophenothiazin-5-ium salts were effective arylation reagents for the base-initiated selective O-arylation and isomerization of α-aryl allylic alcohols. This reaction represents the first use of arylsulfonium salts as arylation reagents to access aryl enol ethers directly from allylic alcohols.

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BACKGROUND: Depression is widely recognized as a common non-motor symptom of Parkinson's disease (PD). Across different studies, the reported prevalence of depression in PD varies widely, ranging from 2.7% to 90%, but it is unclear whether this association is due to genetic or acquired factors. Whether there is a causal relationship remains unknown. The aim of this study was to use a two-sample Mendelian randomization (MR) approach to investigate the causal effect of PD on depression. METHODS: Analyses were conducted separately for individuals of European and East Asian ancestry using publicly available summary data from genome-wide association studies. Depression was divided into two categories: ever depressed for a whole week and major depressive disorder (MDD). PD data were used as the exposure and were obtained from the International Parkinson's Disease Genomics Consortium and the BioBank Japan PheWeb, while depression data were used as the outcome and were obtained from the ntegrative Epidemiology Unit (IEU) Open GWAS Project(A public GWAS database） and the Psychiatric Genomics Consortium. The influence of PD on depression was assessed using inverse variance weighted (IVW), weighted median, MR-Egger, and weighted mode methods. Heterogeneity and pleiotropy were tested, and the results were validated using FinnGen GWAS data from version R9. RESULTS: In individuals of European ancestry, there was a causal relationship between PD and ever depressed for a whole week (IVW method, odds ratio [OR] = 0.990; 95% CI, 0.984-0.996; p = .002), but no causal relationship was observed between PD and MDD (IVW method, OR = 0.974; 95% CI, 0.942-1.009; p = .141). In individuals of East Asian ancestry, no causal relationship was observed between PD and ever depressed for a whole week (IVW method, OR = 1.001; 95% CI, 0.829-1.209; p = .990) and between PD and MDD (IVW method, OR = 1.017; 95% CI, 0.982-1.052; p = .342). The results of the three additional analysis methods were similar to those of the IVW method, and there was no heterogeneity according to Cochran's Q-test. There was no evidence of pleiotropy based on MR-Egger intercept test and MR-PRESSO. The FinnGen validation dataset supported these findings. The results are stable and reliable. CONCLUSION: The observed increase in depression among PD patients could potentially be attributed to modifiable acquired factors. Consequently, there is an urgent need to strengthen the management of PD patients in order to prevent the development of depression in the future.

Asunto(s)

Pueblo Asiatico , Trastorno Depresivo Mayor , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Enfermedad de Parkinson , Humanos , Enfermedad de Parkinson/genética , Enfermedad de Parkinson/epidemiología , Trastorno Depresivo Mayor/genética , Trastorno Depresivo Mayor/epidemiología , Pueblo Asiatico/genética , Población Blanca/genética , Depresión/genética , Depresión/epidemiología , Predisposición Genética a la Enfermedad

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miR-31 is a highly conserved microRNA that plays crucial roles in cell proliferation, migration and differentiation. We discovered that miR-31 and some of its validated targets are enriched on the mitotic spindle of the dividing sea urchin embryo and mammalian cells. Using the sea urchin embryo, we found that miR-31 inhibition led to developmental delay correlated with increased cytoskeletal and chromosomal defects. We identified miR-31 to directly suppress several actin remodeling transcripts, including ß-actin, Gelsolin, Rab35 and Fascin. De novo translation of Fascin occurs at the mitotic spindle of sea urchin embryos and mammalian cells. Importantly, miR-31 inhibition leads to a significant a increase of newly translated Fascin at the spindle of dividing sea urchin embryos. Forced ectopic localization of Fascin transcripts to the cell membrane and translation led to significant developmental and chromosomal segregation defects, highlighting the importance of the regulation of local translation by miR-31 at the mitotic spindle to ensure proper cell division. Furthermore, miR-31-mediated post-transcriptional regulation at the mitotic spindle may be an evolutionarily conserved regulatory paradigm of mitosis.

Asunto(s)

MicroARNs , Biosíntesis de Proteínas , Huso Acromático , Animales , MicroARNs/metabolismo , MicroARNs/genética , Huso Acromático/metabolismo , Regulación del Desarrollo de la Expresión Génica , Humanos , Proteínas de Microfilamentos/metabolismo , Proteínas de Microfilamentos/genética , Mitosis/genética , Proteínas Portadoras/metabolismo , Proteínas Portadoras/genética , Desarrollo Embrionario/genética , Embrión no Mamífero/metabolismo , Segregación Cromosómica/genética , Actinas/metabolismo , Actinas/genética , Erizos de Mar/embriología , Erizos de Mar/genética , Erizos de Mar/metabolismo

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The clinical application of 5-fluorouracil (5-Fu), a potent chemotherapeutic agent, is often hindered by its well-documented cardiotoxic effects. Nevertheless, natural polyphenolic compounds like resveratrol (RES), known for their dual anti-tumor and cardioprotective properties, are potential adjunct therapeutic agents. In this investigation, we examined the combined utilization of RES and 5-Fu for the inhibition of gastric cancer using both in vitro and in vivo models, as well as their combined impact on cardiac cytotoxicity. Our study revealed that the co-administration of RES and 5-Fu effectively suppressed MFC cell viability, migration, and invasion, while also reducing tumor weight and volume. Mechanistically, the combined treatment prompted p53-mediated apoptosis and autophagy, leading to a considerable anti-tumor effect. Notably, RES mitigated the heightened oxidative stress induced by 5-Fu in cardiomyocytes, suppressed p53 and Bax expression, and elevated Bcl-2 levels. This favorable influence enhanced primary cardiomyocyte viability, decreased apoptosis and autophagy, and mitigated 5-Fu-induced cardiotoxicity. In summary, our findings suggested that RES holds promise as an adjunct therapy to enhance the efficacy of gastric cancer treatment in combination with 5-Fu, while simultaneously mitigating cardiotoxicity.

Asunto(s)

Apoptosis , Supervivencia Celular , Fluorouracilo , Resveratrol , Neoplasias Gástricas , Resveratrol/farmacología , Resveratrol/uso terapéutico , Fluorouracilo/farmacología , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/patología , Animales , Apoptosis/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Línea Celular Tumoral , Cardiotónicos/farmacología , Cardiotónicos/uso terapéutico , Estilbenos/farmacología , Estilbenos/uso terapéutico , Humanos , Estrés Oxidativo/efectos de los fármacos , Antimetabolitos Antineoplásicos/farmacología , Autofagia/efectos de los fármacos , Masculino , Miocitos Cardíacos/efectos de los fármacos , Ratones , Movimiento Celular/efectos de los fármacos

RESUMEN

Characterizing the nature of hydrodynamical transport properties in quantum dynamics provides valuable insights into the fundamental understanding of exotic non-equilibrium phases of matter. Experimentally simulating infinite-temperature transport on large-scale complex quantum systems is of considerable interest. Here, using a controllable and coherent superconducting quantum simulator, we experimentally realize the analog quantum circuit, which can efficiently prepare the Haar-random states, and probe spin transport at infinite temperature. We observe diffusive spin transport during the unitary evolution of the ladder-type quantum simulator with ergodic dynamics. Moreover, we explore the transport properties of the systems subjected to strong disorder or a tilted potential, revealing signatures of anomalous subdiffusion in accompany with the breakdown of thermalization. Our work demonstrates a scalable method of probing infinite-temperature spin transport on analog quantum simulators, which paves the way to study other intriguing out-of-equilibrium phenomena from the perspective of transport.

RESUMEN

Specific mechanisms of precipitation change due to global climate variability on plant communities in coastal salt marsh ecosystems remain unknown. Hence, a field manipulative precipitation experiment was established in 2014 and 5 years of field surveys of vegetation from 2017 to 2021 to explore the effects of precipitation changes on plant community composition. The results showed that changes in plant community composition were driven by dominant species, and that the dominance of key species changed significantly with precipitation gradient and time, and that these changes ultimately altered plant community traits (i.e., community density, height, and species richness). Community height increased but community density decreased with more precipitation averaged five years. Furthermore, changes in precipitation altered dominant species composition and functional groups mainly by influencing soil salinity. Salinity stress caused by decreased precipitation shifted species composition from a dominance of taller perennials and grasses to dwarf annuals and forbs, while the species richness decreased. Conversely, soil desalination caused by increased precipitation increased species richness, especially increasing in the dominance of grasses and perennials. Specifically, Apocynaceae became dominance from rare while Amaranthaceae decreased in response to increased precipitation, but Poaceae was always in a position of dominance. Meanwhile, the dominance of grasses and perennials has the cumulative effect of years and their proportion increased under the increased 60% of ambient precipitation throughout the years. However, the annual forb Suaeda glauca was gradually losing its dominance or even becoming extinct over years. Our study highlights that the differences in plant salinity tolerance are key to the effects of precipitation changes on plant communities in coastal salt marsh. These findings aim to provide a theoretical basis for predicting vegetation dynamics and developing ecological management strategies to adapt to future precipitation changes.

Asunto(s)

Salinidad , Suelo , Humedales , Suelo/química , Ecosistema , Plantas , Biodiversidad , Lluvia , Poaceae/crecimiento & desarrollo

RESUMEN

MICB*002:06 differs from MICB*002:01:01 by one nucleotide change at nucleotide 33 in exon 1 from C to T.

Asunto(s)

Exones , Antígenos de Histocompatibilidad Clase I , Humanos , Antígenos de Histocompatibilidad Clase I/genética , Antígenos de Histocompatibilidad Clase I/inmunología , Alelos , Secuencia de Bases , Análisis de Secuencia de ADN/métodos , Prueba de Histocompatibilidad , Alineación de Secuencia , Codón

RESUMEN

BACKGROUND: There is an urgent need to develop an efficient therapeutic strategy for heart failure with preserved ejection fraction (HFpEF), which is mediated by phenotypic changes in cardiac macrophages. We previously reported that vitamin B-6 inhibits macrophage-mediated inflammasome activation. OBJECTIVES: We sought to examine whether the prophylactic use of vitamin B-6 prevents HFpEF. METHODS: HFpEF model was elicited by a combination of high-fat diet and Nω-nitro-l-arginine methyl ester supplement in mice. Cardiac function was assessed using conventional echocardiography and Doppler imaging. Immunohistochemistry and immunoblotting were used to detect changes in the macrophage phenotype and myocardial remodeling-related molecules. RESULTS: Co-administration of vitamin B-6 with HFpEF mice mitigated HFpEF phenotypes, including diastolic dysfunction, cardiac macrophage phenotypic shifts, fibrosis, and hypertrophy. Echocardiographic improvements were observed, with the E/E' ratio decreasing from 42.0 to 21.6 and the E/A ratio improving from 2.13 to 1.17. The exercise capacity also increased from 295.3 to 657.7 min. However, these beneficial effects were negated in downstream of kinase (DOK) 3-deficient mice. Mechanistically, vitamin B-6 increased DOK3 protein concentrations and inhibited macrophage phenotypic changes, which were abrogated by an AMP-activated protein kinase inhibitor. CONCLUSIONS: Vitamin B-6 increases DOK3 signaling to lower risk of HFpEF by inhibiting phenotypic changes in cardiac macrophages.

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Intestinal barrier hemostasis is the key to health. As a resveratrol analogue, pterostilbene (PT) has been reported to prevent dextran sodium sulfate (DSS)-induced intestinal barrier dysfunction mainly associated with the intestinal NF-κB signaling pathway. However, the exact underlying mechanisms are not yet well-defined yet. In this study, we performed RNA-sequencing analysis and unexpectedly found that alarmin S100A8 sensitively responded to DSS-induced intestinal injury. Accordingly, histologic assessments suggested that the high expression of S100A8 was accompanied by increased intestinal infiltration of macrophages, upregulated intestinal epithelial Toll-like receptor 4 (TLR-4), and activated NF-κB signaling pathway. Interestingly, the above phenomena were effectively counteracted upon the addition of PT. Furthermore, by using a coculture system of macrophage THP-1 cells and HT-29 colon cells, we identified macrophage-secreted S100A8 activated intestinal epithelial NF-κB signaling pathway through TLR-4. Taken together, these findings suggested that PT ameliorated DSS-induced intestinal barrier injury through suppression of the macrophage S100A8-intestinal epithelial TLR-4-NF-κB signaling cascade.

Asunto(s)

Calgranulina A , Sulfato de Dextran , Mucosa Intestinal , Ratones Endogámicos C57BL , FN-kappa B , Transducción de Señal , Estilbenos , Receptor Toll-Like 4 , Sulfato de Dextran/efectos adversos , Receptor Toll-Like 4/genética , Receptor Toll-Like 4/metabolismo , FN-kappa B/genética , FN-kappa B/metabolismo , Animales , Transducción de Señal/efectos de los fármacos , Humanos , Ratones , Calgranulina A/genética , Calgranulina A/metabolismo , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/metabolismo , Estilbenos/farmacología , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Macrófagos/inmunología , Masculino , Colitis/inducido químicamente , Colitis/tratamiento farmacológico , Colitis/metabolismo , Colitis/genética

RESUMEN

Receptor-binding peptides are promising candidates for tumor target therapy. However, the inability to occupy "hot spots" on the PPI interface and rapid metabolic instability are significant limitations to their clinical application. We investigated a new strategy in which an FGFR1-binding peptide (Pep1) was site-specifically functionalized with the dinitrophenyl (DNP) hapten at the C-terminus. The resulting Pep1-DNP conjugates retained FGFR1 binding affinity and exhibited a similar potency in inhibiting FGF2-dependent cell proliferation, comparable to that of native Pep1 in vitro. In addition, three conjugates could recruit anti-DNP antibodies onto the surface of cancer cells, thereby mediating the CDC efficacy. In vivo pharmacokinetic studies and antitumor studies demonstrated that optimal conjugate 9 exhibited significantly prolonged half-lives and improved antitumor efficacy without prominent toxicity compared to those of native Pep1. This is a general and cost-effective approach for generating peptidomimetic immunotherapeutics with multiple antitumor mechanisms that may have broad applications in cancer therapy.

Asunto(s)

Neoplasias Pulmonares , Peptidomiméticos , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos/antagonistas & inhibidores , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos/metabolismo , Humanos , Animales , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Peptidomiméticos/química , Peptidomiméticos/farmacología , Peptidomiméticos/síntesis química , Ratones , Péptidos/química , Péptidos/síntesis química , Péptidos/farmacología , Proliferación Celular/efectos de los fármacos , Inmunoterapia , Antineoplásicos/síntesis química , Antineoplásicos/farmacología , Antineoplásicos/química , Línea Celular Tumoral , Femenino , Ratones Endogámicos BALB C

RESUMEN

Salt stress has a detrimental impact on both plant growth and global crop yields. B-box proteins have emerged as pivotal players in plant growth and development regulation. Although the precise role of B-box proteins orchestrating salt stress responses in B. napus (Brassica napus) is not well understood in the current literature, further research and molecular explorations are required. Here, we isolated the B-box protein BnBBX22.A07 from B. napus. The overexpression of BnBBX22.A07 significantly improved the salt tolerance of Arabidopsis (Arabidopsis thaliana) and B. napus. Transcriptomic and histological analysis showed that BnBBX22.A07 enhanced the salt tolerance of B. napus by activating the expression of reactive oxygen species (ROS) scavenging-related genes and decreasing salt-induced superoxide anions and hydrogen peroxide. Moreover, BnBBX22.A07 interacted with BnHY5.C09, which specifically bound to and activated the promoter of BnWRKY33.C03. The presence of BnBBX22.A07 enhanced the activation of BnHY5.C09 on BnWRKY33.C03. Overexpression of BnHY5.C09 and BnWRKY33.C03 improved the salt tolerance of Arabidopsis. Functional analyses revealed that BnBBX22.A07-mediated salt tolerance was partly dependent on WRKY33. Taken together, we demonstrate that BnBBX22.A07 functions positively in salt responses not only by activating ROS scavenging-related genes but also by indirectly activating BnWRKY33.C03. Notably, our study offers a promising avenue for the identification of candidate genes that could be harnessed in breeding endeavours to develop salt-resistant transgenic crops.

RESUMEN

Two-coordinate Au(I) complexes with a donor-metal-acceptor (D-M-A) structure have shown rich luminescent properties. However, charge-neutral dinuclear donor-metal-acceptor type Au(I) complexes featuring aurophilic interactions have been seldom explored. Herein, we describe the structures and photoluminescence properties of two dinuclear Au(I) complexes, namely DiAu-Ph and DiAu-Me. Single crystal X-ray structural analysis of DiAu-Ph reveals a short intramolecular Au-Au distance of 3.224 Å. In dilute solution and doped films, excitation wavelength dependent multiple phosphorescence phenomena were observed for these dinuclear complexes. Theoretical calculations reveal that the aurophilic interaction causes increased contribution of the Au d orbital to the highest occupied molecular orbitals. Thus, the gap between singlet and triplet excited states (ΔEST) is enlarged, which disables the thermally activated delayed fluorescence (TADF). Moreover, the large energy separation (0.45-0.52 eV) and the different orbital configurations between the various excited states result in an inefficient internal conversion, accounting for their multiple phosphorescence properties.

RESUMEN

OBJECTIVE: To explore the potential action mechanism of Huotu Jiji Pellets (HJP) in the treatment of erectile dysfunction (ED) based on network pharmacology and molecular docking. METHODS: We identified the main effective compounds and active molecular targets of HJP from the database of Traditional Chinese Medicine Systems Pharmacology (TCMSP) and Integrative Pharmacology-Based Research Platform of Traditional Chinese Medicine (TCMIP) and the therapeutic target genes of ED from the databases of Genecards. Then we obtained the common targets of HJP and ED using the Venny software, constructed a protein-protein interaction (PPI) network of HJP acting on ED, and screened out the core targets with the Cytoscape software. Lastly we performed GO functional enrichment and KEGG pathway enrichment analyses of the core targets followed by molecular docking of HJP and the core targets using Chem3D and AutoDock Tools and QuickVina-W software. RESULTS: A total of 64 effective compounds, 822 drug-related targets, 1 783 disease-related targets and 320 common targets were obtained in this study. PPI network analysis showed that the core targets of HJP for ED included ESR1, HSP90AA1, SRC, and STAT3. GO functional enrichment analysis indicated the involvement of the core targets in such biological processes as response to xenobiotic stimulus, positive regulation of kinase activity, and positive regulation of MAPK cascade. KEGG pathway enrichment analysis suggested that PI3K-Akt, apoptosis, MAPK, HIF-1, VEGF, autophagy and other signaling pathways may be related to the mechanism of HJP acting on ED. Molecular docking prediction exhibited a good docking activity of the key active molecules of HJP with the core targets. CONCLUSION: This study showed that HJP acted on ED through multi-components, multi-targets and multi-pathways, which has provided some evidence and reference for the clinical treatment and subsequent studies of the disease.

Asunto(s)

Medicamentos Herbarios Chinos , Disfunción Eréctil , Medicina Tradicional China , Simulación del Acoplamiento Molecular , Farmacología en Red , Mapas de Interacción de Proteínas , Masculino , Disfunción Eréctil/tratamiento farmacológico , Medicamentos Herbarios Chinos/uso terapéutico , Medicamentos Herbarios Chinos/farmacología , Humanos , Transducción de Señal

RESUMEN

The non-classical HLA-G*01:55 allele differs from G*01:01:12 at one position in exon 4.

Asunto(s)

Alelos , Pueblo Asiatico , Exones , Antígenos HLA-G , Prueba de Histocompatibilidad , Humanos , Antígenos HLA-G/genética , Secuencia de Bases , Análisis de Secuencia de ADN , China , Codón , Pueblos del Este de Asia

RESUMEN

[This corrects the article DOI: 10.3389/fcell.2021.793073.].

RESUMEN

Background: Breviscapine has been demonstrated to have beneficial effects in ameliorating acute lung injury (ALI), yet its potential therapeutic value and molecular mechanisms in sepsis-induced ALI remain unexplored. Methods: We utilized network pharmacology approach to identify the potential targets and mechanisms of breviscapine in treating sepsis-induced ALI. To construct a murine model of sepsis, we performed cecal ligation and puncture (CLP). Hematoxylin and eosin (HE) staining and enzyme-linked immunosorbent assay (ELISA) were employed to respectively determine the pathologic changes and levels of inflammatory factors. Neutrophil count and total protein level in bronchoalveolar lavage fluid (BALF) were detected by corresponding kit. Additionally, we utilized flow cytometry, immunofluorescence, Western blotting, and real-time reverse transcription PCR (qRT-PCR) to detect cell apoptosis, protein expression, and gene expression. Finally, we used ELISA kits to detect the activity of myeloperoxidase (MPO) and caspase-8 (CASP8). Results: Breviscapine was revealed to target 81 potential proteins in the treatment of sepsis-induced ALI, while CASP8 was the most important one as demonstrated by network analysis. In vivo experiments demonstrated that breviscapine effectively reduced the severity of sepsis-induced ALI and inflammation, and significantly suppressed neutrophil infiltration in the lung tissues of CLP mice and promoted neutrophil apoptosis in the peripheral blood. In vitro experiments revealed that lipopolysaccharide (LPS)-induced neutrophil apoptosis was inhibited, and the expression and activity of CASP8 were down-regulated. Breviscapine intervention markedly up-regulated the expression and activity of CASP8, consequently activating neutrophil apoptosis and inhibiting inflammatory response by activating the NF-κB signaling pathway. Conclusion: Breviscapine is remarkably effective in improving sepsis-induced ALI, and its mechanism of action may be to induce neutrophil apoptosis, inhibit inflammatory overreaction and reduce its infiltration in pulmonary tissues by up-regulating the expression and activity of CASP8.