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Hepatocellular carcinoma (HCC) remains a major global health concern with limited therapeutic options and poor prognosis. Chemokines have emerged as critical regulators in the progression and metastasis of HCC. This study aims to investigate the mechanisms involved in CCL28-promoted progression of HCC and provide novel therapeutic targets for HCC treatment. Relationship between CCL28 expression and HCC progression were investigated by bioinformatic analysis and immunohistochemical staining assays. CCK-8, Transwell, and colony formation assay were conducted to explore the impact of CCL28 on the growth, migration and invasion of HCC cells. Quantitative real-time PCR and western blotting assays were performed to learn potential molecular mechanisms underlying the transformation of HCC driven by CCL28. The results showed that there was a direct link between increased CCL28 levels and the advancement of HCC, leading to a worse outcome. CCL28 significantly augmented malignant transformation of HCC cells, containing proliferation, migration, invasion, and clonogenicity, via activation of PDGFD-regulated MMP9 and VEGFA pathways. CCL28 emerges as a pivotal contributor to HCC tumorigenesis, propelling HCC development through the PDGFD signaling pathway. Our findings unveil potential therapeutic targets for HCC treatment.
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The incidence of ulcerative colitis (UC) is increasing annually, and UC has a serious impact on patients' lives. Polysaccharides have gained attention as potential drug candidates for treating ulcerative colitis (UC) in recent years. Huaier (Trametes robiniophila Murr) is a fungus that has been used clinically for more than 1000 years, and its bioactive polysaccharide components have been reported to possess immunomodulatory effects, antitumour potential, and renoprotective effects. In this study, we aimed to examine the protective effects and mechanisms of Huaier polysaccharide (HP) against UC. Based on the H2O2-induced oxidative stress model in HT-29 cells and the dextran sulphate sodium salt (DSS)-induced UC model, we demonstrated that Huaier polysaccharides significantly alleviated DSS-induced colitis (weight loss, elevated disease activity index (DAI) scores, and colonic shortening). In addition, HP inhibited oxidative stress and inflammation and alleviated DSS-induced intestinal barrier damage. It also significantly promoted the expression of the mucin Muc2. Furthermore, HP reduced the abundance of harmful bacteria Escherichia-Shigella and promoted the abundance of beneficial bacteria Muribaculaceae_unclassified, Anaerotruncus, and Ruminococcaceae_unclassified to regulate the intestinal flora disturbance caused by DSS. Nontargeted metabolomics revealed that HP intervention would modulate metabolism by promoting levels of 3-hydroxybutyric acid, phosphatidylcholine (PC), and phosphatidylethanolamine (PE). These results demonstrated that HP had the ability to mitigate DSS-induced UC by suppressing oxidative stress and inflammation, maintaining the intestinal barrier, and modulating the intestinal flora. These findings will expand our knowledge of how HP functions and offer a theoretical foundation for using HP as a potential prebiotic to prevent UC.
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Sulfato de Dextrana , Microbioma Gastrointestinal , Estresse Oxidativo , Polissacarídeos , Microbioma Gastrointestinal/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Animais , Humanos , Polissacarídeos/farmacologia , Camundongos , Masculino , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/microbiologia , Modelos Animais de Doenças , Inflamação/tratamento farmacológico , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Células HT29 , Camundongos Endogâmicos C57BL , Colite/induzido quimicamente , Colite/tratamento farmacológicoRESUMO
Macrophages (Mφs) play a crucial role in the homeostasis of the periapical immune micro-environment caused by bacterial infection. Mφ efferocytosis has been demonstrated to promote the resolution of multiple infected diseases via accelerating Mφ polarization into M2 type. However, the Mφ efferocytosis-apical periodontitis (AP) relationship has not been elucidated yet. This study aimed to explore the role of Mφ efferocytosis in the pathogenesis of AP. Clinical specimens were collected to determine the involvement of Mφ efferocytosis in the periapical region via immunohistochemical and immunofluorescence staining. For a further understanding of the moderator effect of Mφ efferocytosis in the pathogenesis of AP, both an in vitro AP model and in vivo AP model were treated with ARA290, a Mφ efferocytosis agonist. Histological staining, micro-ct, flow cytometry, RT-PCR and Western blot analysis were performed to detect the inflammatory status, alveolar bone loss and related markers in AP models. The data showed that Mφ efferocytosis is observed in the periapical tissues and enhancing the Mφ efferocytosis ability could effectively promote AP resolution via facilitating M2 Mφ polarization. Collectively, our study demonstrates the functional importance of Mφ efferocytosis in AP pathology and highlights that accelerating Mφ efferocytosis via ARA290 could serve as an adjuvant therapeutic strategy for AP.
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Eferocitose , Periodontite Periapical , Humanos , Tecido Periapical , Adjuvantes Imunológicos , MacrófagosRESUMO
BACKGROUND: Diabetic patients with cataracts encounter specific difficulties during cataract surgery due to alterations in microcirculation, blood supply, metabolism, and the microenvironment. Traditional phacoemulsification may not fully tackle these issues, especially in instances with substantial preoperative astigmatism. The utilization of femtosecond laser-assisted phacoemulsification, in conjunction with Toric intraocular lens (IOL) implantation, offers a potentially more efficient strategy. This research seeks to evaluate the efficacy and possible complications of this approach in diabetic cataract patients. AIM: To investigate the clinical efficacy and complications of femtosecond laser-assisted phacoemulsification combined with Toric IOL implantation in diabetic cataract patients, comparing it with traditional phacoemulsification methods. METHODS: This retrospective study enrolled 120 patients with diabetes cataract from May 2019 to May 2021. The patients were divided into two groups: the control group underwent traditional phacoemulsification and Toric IOL implantation, while the treatment group received Len Sx femtosecond laser-assisted treatment. Outcome measures included naked eye vision, astigmatism, high-level ocular phase difference detection, clinical efficacy, and complication. RESULTS: There were no significant preoperative differences in astigmatism or naked eyesight between the two groups. However, postoperative improvements were observed in both groups, with the treatment group showing greater enhancements in naked eye vision and astigmatism six months after the procedure. High-level corneal phase difference tests also indicated significant differences in favor of the treatment group. CONCLUSION: This study suggests that femtosecond laser-assisted phacoemulsification combined with Toric IOL implantation appears to be more effective in enhancing postoperative vision in diabetic cataract patients compared to traditional methods offering valuable insights for clinical practice.
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OBJECTIVE: The purpose of this study was to assess the composition of the oral microbial flora of adults with rampant caries in China to provide guidance for treatment. PATIENTS AND METHODS: Sixty human salivary and supragingival plaque samples were collected. They were characterized into four groups: patients with rampant caries with Sjogren's syndrome (RC-SS) or high-sugar diet (RC-HD), common dental caries (DC), and healthy individuals (HP). The 16S rRNA V3-V4 region of the bacterial DNA was detected by Illumina sequencing. PCoA based on OTU with Bray-Curtis algorithm, the abundance of each level, LEfSe analysis, network analysis, and PICRUSt analysis were carried out between the four groups and two sample types. Clinical and demographic data were compared using analysis of variance (ANOVA) or the nonparametric Kruskal-Wallis rank-sum test, depending on the normality of the data, using GraphPad Prism 8 (P < 0.05). RESULTS: OTU principal component analysis revealed a significant difference between healthy individuals and those with RC-SS. In the saliva of patients with rampant caries, the relative abundance of Firmicutes increased significantly at the phylum level. Further, Streptocpccus, Veillonella, Prevotella, and Dialister increased, while Neisseria and Haemophilus decreased at the genus level. Veillonella increased in the plaque samples of patients with rampant caries. CONCLUSION: Both salivary and dental plaque composition were significantly different between healthy individuals and patients with rampant caries. This study provides a microbiological basis for exploring the etiology of rampant caries. CLINICAL RELEVANCE: This study provides basic information on the flora of the oral cavity in adults with rampant caries in China. These findings could serve as a reference for the treatment of this disease.
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Cárie Dentária , Microbiota , Síndrome de Sjogren , Adulto , Humanos , Cárie Dentária/microbiologia , Síndrome de Sjogren/complicações , RNA Ribossômico 16S/genética , Suscetibilidade à Cárie Dentária , Saliva/microbiologia , Bactérias , Microbiota/genética , Açúcares , DietaRESUMO
BACKGROUND: The interplay of tumor-associated macrophages (TAMs) and tumor cells plays a key role in the development of hepatocellular carcinoma (HCC) and provides an important target for HCC therapy. The communication between them is still on the investigation. Bufalin, the active component derived from the traditional Chinese medicine (TCM) Chansu, has been evidenced to possess anti-HCC activity by directly suppressing tumor cells, while its immunomodulatory effect on the tumor microenvironment (TME) is unclear. PURPOSE: To explore the mechanism of M2 TAM-governed tumor cell proliferation and the inhibitory effect of bufalin on HCC growth by targeting M2 macrophages. METHODS: Morphology and marker proteins were detected to evaluate macrophage polarization via microscopy and flow cytometry. Cellular proliferation and malignant transformation of HCC cells cultured with macrophage conditioned medium (CM) or bufalin-primed M2-CM, were assessed by cell viability, colony formation and soft agar assays. Regulations of gene transcription and protein expression and release were determined by RT-qPCR, immunoblotting, immunoprecipitation, ELISA and immunofluorescence. Tumorigenicity upon bufalin treatment was verified in orthotopic and diethylnitrosamine-induced HCC mouse model. RESULTS: In this study, we first verified that M2 macrophages secreted Wnt1, which acted as a mediator to trigger ß-catenin activation in HCC cells, leading to cellular proliferation. Bufalin suppressed HCC cell proliferation and malignant transformation by inhibiting Wnt1 release in M2 macrophages, and dose-dependently inhibited HCC progression in mice. Mechanistically, bufalin specially targeted to block Wnt1 transcription, thus inactivating ß-catenin signaling cascade in HCC cells and leading to tumor regression in HCC mouse model. CONCLUSION: These results clearly reveal a novel potential of bufalin to suppress HCC through immunomodulation, and shed light on a new M2 macrophage-based modality of HCC immunotherapy, which additively enhances direct tumor-inhibitory efficacy of bufalin.
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Bufanolídeos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Animais , Camundongos , Carcinoma Hepatocelular/metabolismo , beta Catenina/metabolismo , Neoplasias Hepáticas/metabolismo , Linhagem Celular Tumoral , Macrófagos/metabolismo , Carcinogênese , Microambiente TumoralRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine (TCM) holds that non-alcoholic fatty liver disease (NAFLD) belong to the category of "thoracic fullness". Polygonum perfoliatum L. (PPL), a Chinese medicinal herb with the effect of treating thoracic fullness, was recorded in the ancient Chinese medicine book "Supplements to Compendium of Materia Medica". It has been used since ancient times to treat NAFLD. However, the underlying mechanism and active components of PPL against NAFLD remains unclear. AIM OF STUDY: To identify the main active components and the anti-NAFLD mechanism of PPL. MATERIALS AND METHODS: Network pharmacology, UPLC/QE-HFX analysis, and molecular docking were employed to determine the main bioactive compounds and key targets of PPL for the NAFLD treatment. This effect was further validated with administration of PPL (200 mg/kg and 400 mg/kg) to NAFLD model mice for 5 weeks. Systemic signs of obesity, biochemical parameters, and histological changes were characterized. Immunohistochemistry, western blot, and PCR analysis were conducted to elucidate the mechanistic pathways through which PPL exerts its effects. RESULTS: Network pharmacology revealed 77 crossover genes between the PPL and NAFLD. The kyoto encyclopedia of genes and genomes (KEGG) analysis show that PPL treat NAFLD mainly regulating glucose-lipid metabolism mediated by PI3K/AKT signal pathway. The Gene Ontology (GO) enrichment analysis show that PPL treat NAFLD mainly regulating inflammation mediated by cytokine-mediated signaling pathway. In accordance with the anticipated outcomes, administration of PPL in a dose-dependent manner effectively mitigated insulin resistance induced by a high-fat diet (HFD) by activating the PI3K/AKT signaling pathway. Histopathological evaluation corroborated the hepatoprotective effects of PPL against HFD-induced hepatic steatosis, as evidenced by the inhibition of de novo fatty acid synthesis and promotion of fatty acid ß-oxidation (FAO). Further research showed that PPL blocked cytokine production by inhibiting the NF-κB pathway, thereby reducing immune cell infiltration. Furthermore, five flavonoids from PPL, including quercetin, baicalein, galangin, apigenin, and genistein were identified as key compounds based on ingredient-target-pathway network analysis. Molecular docking show that these active compounds have favorable binding interactions with AKT1, PIK3R1, and MAPK1, further confirming the impact of PPL on the PI3K/AKT pathway. CONCLUSIONS: Through the combination of network pharmacology prediction and experimental validation, this work determined that therapeutic effect of PPL on NAFLD, and such protective effect is mediated by activating PI3K/AKT-mediated glucolipid metabolism pathway and hepatic NF-κB-mediated cytokine signaling pathway.
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Hepatopatia Gordurosa não Alcoólica , Polygonum , Animais , Camundongos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , NF-kappa B , Simulação de Acoplamento Molecular , Farmacologia em Rede , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Ácidos Graxos , CitocinasRESUMO
Natural products have been used extensively around the world for many years as therapeutic, prophylactic, and health-promotive agents. Ribes himalense Royle ex Decne, a plant used in traditional Tibetan medicine, has been demonstrated to have significant antioxidant and anti-inflammatory properties. However, the material basis of its medicinal effects has not been sufficiently explored. In this study, we established an integrated strategy by online HPLC-1,1-diphenyl-2-picrylhydrazyl, medium-pressure liquid chromatography, and HPLC to achieve online detection and separation of antioxidants in Ribes himalense extracts. Finally, four antioxidants with quercetin as the parent nucleus were obtained, namely, Quercetin-3-O-ß-D-glucopyranoside-7-O-α-L-rhamnopyranoside, Quercetin-3-O-ß-D-xylopyranosyl(1-2)-ß-D-glucopyranoside, Quercetin-3-O-ß-D-glucopyranoside, and Quercetin-3-O-ß-D-galactoside. Until now, the four antioxidants in Ribes himalense have not been reported in other literatures. Meanwhile, the free-radical-scavenging ability of them was evaluated by DPPH assay, and potential antioxidant target proteins were explored using molecular docking. In conclusion, this research provides insights into the active compounds in Ribes himalense which will facilitate the advancement of deeper studies on it. Moreover, such an integrated chromatographic strategy could be a strong driver for more efficient and scientific use of other natural products in the food and pharmaceutical industries.
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Drought adaptation of plants is closely related to resistance and tolerance to drought stress as well as the ability to recover after the elimination of the stress. Glycyrrhiza uralensis Fisch is a commonly applied herb whose growth and development are greatly affected by drought. Here, we provide the first comprehensive analysis of the transcriptomic, epigenetic, and metabolic responses of G. uralensis to drought stress and rewatering. The hyper-/hypomethylation of genes may lead to up-/downregulated gene expression, and epigenetic changes can be regarded as an important regulatory mechanism of G. uralensis under drought stress and rewatering. Moreover, integrated transcriptome and metabolome analysis revealed that genes and metabolites involved in pathways of antioxidation, osmoregulation, phenylpropanoid biosynthesis, and flavonoid biosynthesis may regulate the drought adaptation of G. uralensis. This work provides crucial insights into the drought adaptation of G. uralensis and offers epigenetic resources for cultivating G. uralensis with high drought adaptation.
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Glycyrrhiza uralensis , Glycyrrhiza , Glycyrrhiza uralensis/genética , Glycyrrhiza uralensis/metabolismo , Multiômica , Secas , Antioxidantes/metabolismo , Transcriptoma , Glycyrrhiza/genéticaRESUMO
Radiation-induced lung injury (RILI), a potentially fatal and dose-limiting complication of radiotherapy for thoracic tumors, is divided into early reversible pneumonitis and irreversible advanced-stage fibrosis. Early detection and intervention contribute to improving clinical outcomes of patients. However, there is still a lack of reliable biomarkers for early prediction and clinical diagnosis of RILI. Given the central role of inflammation in the initiation and progression of RILI, we explored specific inflammation-related biomarkers during the development of RILI in this study. Two expression profiles from the Gene Expression Omnibus (GEO) database were downloaded, in which 75 differentially expressed genes (DEGs) were screened out. Combining Gene Oncology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and protein-protein interaction (PPI) network analysis, we identified four inflammation-related hub genes in the progression of RILI-MMP9, IL-1ß, CCR1 and S100A9. The expression levels of the hub genes were verified in RILI mouse models, with S100A9 showing the highest level of overexpression. The level of S100A9 in bronchoalveolar lavage fluid (BALF) and the expression of S100A9 in lung tissues were positively correlated with the degree of inflammation in RILI. The results above indicate that S100A9 is a potential biomarker for the early prediction and diagnosis of the development of RILI.
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BACKGROUND: Exosomes are essential for hepatocellular carcinoma (HCC) progression and have garnered significant interest as novel targets for diagnostic, prognostic, and therapeutic approaches. This study aims to identify potential exosome-related biomarkers for the development of useful strategies for HCC diagnosis and therapy. METHODS: Three datasets obtained from the Gene Expression Omnibus (GEO) were utilized to identify differentially expressed genes (DEGs) in HCC. Through Gene Ontology (GO) analysis and protein-protein interaction (PPI) network, overall survival (OS) analysis, Cox analyses, and diethylnitrosamine (DEN)-induced HCC mouse model detection, exosome-related hub gene was screened out, followed by a prognostic value assessment and immune-correlates analysis based on the Cancer Genome Atlas (TCGA) dataset. The hub gene-containing exosomes derived from Hepa1-6 cells were isolated and characterized using differential ultracentrifugation, transmission electron microscopy scanning, and Western blot. Ultrasound-guided intrahepatic injection, cell co-culture, CCK-8, and flow cytometry were performed to investigate the effects of the hub gene on macrophage infiltration and polarization in HCC. RESULTS: A total of 83 DEGs enriched in the extracellular exosome term, among which, FTCD, HRA, and C8B showed the strongest association with the progression of HCC. FTCD was independently associated with a protective effect in HCC and selected as the hub gene. The presence of FTCD in exosomes was confirmed. FTCD-stimulated macrophages were polarized towards the M1 type and suppressed HCC cells proliferation. CONCLUSIONS: FTCD is a potential exosome-related biomarker for HCC diagnosis, prognosis, and treatment. The crosstalk between FTCD-containing exosomes and macrophages in HCC progression deserves further investigation.
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Carcinoma Hepatocelular , Exossomos , Glutamato Formimidoiltransferase , Neoplasias Hepáticas , Animais , Camundongos , Western Blotting , Carcinoma Hepatocelular/genética , Exossomos/genética , Neoplasias Hepáticas/genética , Camundongos Endogâmicos , Glutamato Formimidoiltransferase/metabolismoRESUMO
Microbial transformation of betulonic acid with Circinella muscae CGMCC 3.2695 yielded nine undescribed metabolites and eight known compounds. The structures of the metabolites were established based on extensive NMR and HR-ESI-MS data analyses. It is shown that C. muscae could catalyze the regioselective hydroxylation at C-2, C-7, C-15, C-16, C-21, and C-30 along with carbonylation at C-2 and C-21. Furthermore, potential anti-neuroinflammatory activities of the obtained compounds in NO production were tested in lipopolysaccharides-induced BV-2 cells. Some of the metabolites exhibited pronounced inhibitory activities with IC50 values of 4.27-16.68 µM.
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With the development of industrialization in recent years, infrasound has become an important component of public noise. To date, diverse studies have revealed the negative effects of infrasound on the central nervous system (CNS), especially the learning and memory ability. It is widely reported that environmental enrichment (EE) ameliorates the learning and memory deficits in different models of brain injury. Therefore, the present study was designed to determine the possible benefits of pre-exposure to EE in preventing functional deficits following infrasound exposure and their related mechanism. Adult male rats were given enriched or standard housing for 30 days. Following enrichment, the rats were exposed to 16 Hz, 130 dB infrasound for 14 days, and then their learning and memory ability was assessed. Changes to neuroinflammation, apoptosis, and oxidative stress in the hippocampus were also detected. Our results showed that the infrasound-induced deficit in learning and memory was attenuated significantly in EE pre-exposed rats. Pre-exposure to EE could induce a decrease in proinflammatory cytokines and increased anti-inflammatory cytokines and antioxidant properties in the hippocampus. Moreover, pre-exposure to EE also exerted antiapoptosis functions by upregulating the B-cell lymphoma/leukemia-2 (Bcl-2) level and downregulating the P53 level in the hippocampus. In conclusion, the results of the present study suggested that EE is neuroprotective when applied before infrasound exposure, resulting in an improved learning and memory ability by enhancing antioxidant, anti-inflammatory, and antiapoptosis capacities.
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Antioxidantes , Transtornos da Memória , Animais , Citocinas , Hipocampo , Aprendizagem , Masculino , Transtornos da Memória/etiologia , RatosRESUMO
Porcine hemagglutinating encephalomyelitis virus (PHEV) is a typical neurotropic betacoronavirus causing digestive disease and/or neurological dysfunction in neonatal pigs. Actin filaments have been identified to implicate in PHEV invasion, but the effects of viral infection on microtubules (MTs) cytoskeleton are unknown. Here, we observed that PHEV infection induced MT depolymerization and was accompanied by the disappearance of microtubule organizing centers. Depolymerization of MTs induced by nocodazole significantly inhibited viral RNA replication, but over-polymerization of MTs induced by paclitaxel did not substantially affect PHEV infection. The expression of histone deacetylase 6 (HDAC6), an important regulator of MT acetylation, progressively increased during PHEV infection. Tramstatin A could alter HDAC6 deacetylase activity to enhance the acetylation of the substrate α-tubulin and MT polymerization, but does not increase PHEV proliferation. These findings suggest that PHEV could subvert host MT cytoskeleton to facilitate infection, and that MT depolymerization negatively affects viral replication independently of HDAC6 activity.
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Betacoronavirus 1 , Infecções por Coronavirus , Doenças dos Suínos , Animais , Betacoronavirus , Infecções por Coronavirus/veterinária , Microtúbulos , Suínos , Tubulina (Proteína)/genética , Tubulina (Proteína)/metabolismo , Replicação ViralRESUMO
BACKGROUND: Immunotherapy for hepatocellular carcinoma (HCC) exhibits limited clinical efficacy due to immunosuppressive tumor microenvironment (TME). Tumor-infiltrating macrophages (TIMs) account for the major component in the TME, and the dominance of M2 phenotype over M1 phenotype in the TIMs plays the pivotal role in sustaining the immunosuppressive character. We thus investigate the effect of bufalin on promoting TIMs polarization toward M1 phenotype to improve HCC immunotherapy. METHODS: The impact of bufalin on evoking antitumor immune response was evaluated in the immunocompetent mouse HCC model. The expression profiling of macrophage-associated genes, surface markers and cytokines on bufalin treatment in vitro and in vivo were detected using flow cytometry, immunofluorescence, western blot analysis, ELISA and RT-qPCR. Cell signaling involved in M1 macrophage polarization was identified via the analysis of gene sequencing, and bufalin-governed target was explored by immunoprecipitation, western blot analysis and gain-and-loss of antitumor immune response. The combination of bufalin and antiprogrammed cell death protein 1 (anti-PD-1) antibody was also assessed in orthotopic HCC mouse model. RESULTS: In this study, we showed that bufalin can function as an antitumor immune modulator that governs the polarization of TIMs from tumor-promoting M2 toward tumor-inhibitory M1, which induces HCC suppression through the activation of effector T cell immune response. Mechanistically, bufalin inhibits overexpression of p50 nuclear factor kappa B (NF-κB) factor, leading to the predominance of p65-p50 heterodimers over p50 homodimers in the nuclei. The accumulation of p65-p50 heterodimers activates NF-κB signaling, which is responsible for the production of immunostimulatory cytokines, thus resulting in the activation of antitumor T cell immune response. Moreover, bufalin enhances the antitumor activity of anti-PD-1 antibody, and the combination exerts synergistic effect on HCC suppression. CONCLUSIONS: These data expound a novel antitumor mechanism of bufalin, and facilitate exploitation of a new potential macrophage-based HCC immunotherapeutic modality.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Animais , Bufanolídeos , Linhagem Celular Tumoral , Citocinas/metabolismo , Humanos , Imunidade , Macrófagos , Camundongos , NF-kappa B/metabolismo , Fenótipo , Microambiente TumoralRESUMO
BACKGROUND: As a severe complication of sepsis, sepsis-associated encephalopathy (SAE) usually manifests as impaired learning and memory ability in survivors. Previous studies have reported that environmental enrichment (EE) can increase the learning and memory ability in different brain injury models. However, there has been no research on the possible positive effect of EE on SAE. AIM: The present study aimed to test the effect of EE on SAE-induced impairment of learning and memory and its related mechanisms. METHODS: A Morris water maze test (MWM) was used to evaluate the learning and memory ability of SAE rats that received EE housing or not. The expression of vasopressin (VP) was assessed using immunofluorescence microscopy and enzyme-linked immunosorbent assays (ELISAs). The synthesis of VP in the supraoptic nucleus (SON) was determined using quantitative real-time reverse transcription-PCR analysis. Moreover, inflammatory markers and brain-derived neurotrophic factor (BDNF) were detected using ELISA. RESULTS: The results showed that SAE induced a decreased learning and memory ability, while EE reversed this impairment. EE also enhanced the synthesis and secretion of VP in the SON. Blocking the action of VP in the hippocampus interrupted the EE-induced amelioration of learning and memory impairment. Moreover, EE induced changes to the levels of BDNF and cytokines in the hippocampus and these effects were mediated by VP binding to the VP receptor 1a. CONCLUSION: Our findings demonstrated that the enhanced synthesis and secretion of VP in the SON are a key determinant responsible for EE-induced alleviation of learning and memory deficits caused by SAE.
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BACKGROUND: One of the most serious complications of sepsis is sepsis-associated encephalopathy (SAE), which impairs the cognition ability of survivors. Environmental enrichment (EE) has been demonstrated to alleviate cognition deficits under many kinds of brain injury conditions. However, EE's effects on SAE remain unknown. Therefore, this study aimed to determine EE's effect on cognition disorders under SAE conditions and the underlying mechanism. MATERIALS AND METHODS: Adult male rats, subject to SAE or not, were housed under a standard environment (SE) or EE for 30 days. Subsequently, the rats were subjected to cognitive tests, such as the novel object recognition (NOR) test, the Morris water maze (MWM) test, an Open Field (OF) test, the elevated plus maze (EPM) test, and a sensory neglect (SN) test. Neuroinflammation, apoptosis, and oxidative stress changes in the brain were also detected. RESULTS: The results revealed that SAE impaired somatesthesia, recognition memory, spatial learning and memory, and exploratory activity, which were significantly improved by EE housing. EE also prevented SAE-induced anxiety-like behavior. In addition, EE housing capable induced a decrease in pro-inflammatory cytokines, and an increase in anti-inflammatory cytokines and antioxidant properties in the brain. Moreover, EE housing exerted an anti-apoptosis function by upregulating the level of B-cell lymphoma/leukemia-2 (Bcl-2) level and downregulating the level of p53 level in the hippocampus. CONCLUSIONS: The results of the present study indicated that EE exerts a neuroprotective function on cognitive ability in SAE rats. The effect is achieved by increasing antioxidants, and anti-inflammatory and antiapoptotic capacities. EE can effectively rescue SAE-induced cognitive deficits.
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Encefalopatias , Transtornos Cognitivos , Disfunção Cognitiva , Encefalopatia Associada a Sepse , Masculino , Animais , Ratos , Encefalopatia Associada a Sepse/etiologia , Encefalopatia Associada a Sepse/prevenção & controle , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/prevenção & controle , Cognição , Encefalopatias/etiologia , Encefalopatias/prevenção & controle , Antioxidantes , CitocinasRESUMO
A triplon refers to a fictitious particle that carries angular momentum S=1 corresponding to the elementary excitation in a broad class of quantum dimerized spin systems. Such systems without magnetic order have long been studied as a testing ground for quantum properties of spins. Although triplons have been found to play a central role in thermal and magnetic properties in dimerized magnets with singlet correlation, a spin angular momentum flow carried by triplons, a triplon current, has not been detected yet. Here we report spin Seebeck effects induced by a triplon current: triplon spin Seebeck effect, using a spin-Peierls system CuGeO3. The result shows that the heating-driven triplon transport induces spin current whose sign is positive, opposite to the spin-wave cases in magnets. The triplon spin Seebeck effect persists far below the spin-Peierls transition temperature, being consistent with a theoretical calculation for triplon spin Seebeck effects.
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ABSTRACT: To compare the clinical efficacy of sodium hyaluronate eye drops, polyethylene glycol eye drops, and compound dextran eye drops in the treatment of dry eye after phacoemulsification of cataract.A total of 99 patients with dry eye after cataract phacoemulsification combined with intraocular lens implantation were treated in our hospital. Patients were divided into group A (sodium hyaluronate eye drops), group B (polyethylene glycol eye drops), and group C (dextran-70 eye drops). The clinical effect, tear film breakup time, basic tear secretion, corneal staining score, dry eye symptom score, and the incidence of ocular irritation were assessed.On the 3rd, 15th, 30th, and 60th day after operation, the tear film breakup time, corneal staining score, Schirmer I test, and dry eye symptom score in group A and group B were better than those in group C (Pâ<â.05). In addition, there were no significant differences in tear breakdown time, corneal staining score, Schirmer I test, and dry eye symptom score between group A and group B (Pâ>â.05). At 3 days to 60âdays after operation, the incidence of dry eye in group A (12.12%) and group B (18.18%) was lower than that in group C (39.39%), and the incidence of dry eye in group A was significantly lower than that in group B (Pâ<â.05).The effect of sodium hyaluronate eye drops elicited a greater beneficial impact as compared to polyethylene glycol eye drops and dextran-70 eye drops.
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Dextranos/administração & dosagem , Ácido Hialurônico/administração & dosagem , Facoemulsificação/efeitos adversos , Polietilenoglicóis/administração & dosagem , Complicações Pós-Operatórias/tratamento farmacológico , Xeroftalmia/tratamento farmacológico , Idoso , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Soluções Oftálmicas/administração & dosagem , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Índice de Gravidade de Doença , Resultado do Tratamento , Xeroftalmia/diagnóstico , Xeroftalmia/epidemiologia , Xeroftalmia/etiologiaRESUMO
Sodium percarbonate (SPC) is considered a potential alternative to liquid hydrogen peroxide (H2O2) in organic compounds contaminated water/soil remediation due to its regularly, transportable, economical, and eco-friendly features. The solid state of SPC makes it more suitable to remediate actual soil and water with a milder H2O2 release rate. Apart from its good oxidative capacity, alkaline SPC can simultaneously remediate acidized solution and soil to the neutral condition. Conventionally, percarbonate-based advanced oxidation process (P-AOPs) system proceed through the catalysis under ultraviolet ray, transition metal ions (i.e., Fe2+, Fe3+, and V4+), and nanoscale zero-valent metals (iron, zinc, copper, and nickel). The hydroxyl radical (â¢OH), superoxide radical (â¢O2-), and carbonate radical anion (â¢CO3-) generated from sodium percarbonate could attack the organic pollutant structure. In this review, we present the advances of P-AOPs in heterogeneous and homogeneous catalytic processes through a wide range of activation methods. This review aims to give an overview of the catalysis and application of P-AOPs for emerging contaminants degradation and act as a guideline of the field advances. Various activation methods of percarbonate are summarized, and the influence factors in the solution matrix such as pH, anions, and cations are thoroughly discussed. Moreover, this review helps to clarify the advantages and shortcomings of P-AOPs in current scientific progress and guide the future practical direction of P-AOPs in sustainable carbon catalysis and green chemistry.