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Depression, recognized globally as a primary cause of disability, has its pathogenesis closely related to neuroinflammation and neuronal damage. Arctiin (ARC), the major bioactive component of Fructus arctii, has various pharmacological activities, such as anti-inflammatory and neuroprotective effects. Building on previous findings that highlighted ARC's capability to mitigate depression by dampening microglial hyperactivation and thereby reducing neuroinflammatory responses and cortical neuronal damage in mice, the current study delves deeper into ARC's therapeutic potential by examining its impact on hippocampal neuronal damage in depression. Utilizing both chronic unpredictable mild stress (CUMS)-induced depression model in mice and corticosterone (CORT)-stimulated PC12 cell model of neuronal damage, the techniques including Nissl staining, immunohistochemistry, western blotting, ELISA, lactate dehydrogenase assays, colony formation assays, immunofluorescence staining and molecular docking were employed to unravel the mechanisms behind ARC's neuroprotective effects. The findings revealed that ARC not only mitigates hippocampal neuropathological damage and reduces serum CORT levels in CUMS-exposed mice but also enhances cell activity while reducing lactate dehydrogenase release in CORT-stimulated PC12 cells. ARC attenuated neuroinflammatory responses and neuronal apoptosis by inhibiting the overactivation of the P2X7 receptor (P2X7R)/NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome signaling pathway, similar to the effect of A438079 (P2X7R antagonist). Interestingly, pretreatment with A438079 blocked the neuroprotective effect of ARC. Computer modeling predicted that both ARC and A438079 have strong binding with P2X7R and they have the same binding site. These results suggested that ARC may exert a neuroprotective role by binding to P2X7R, thereby inhibiting the P2X7R/NLRP3 inflammasome signaling pathway.
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ETHNOPHARMACOLOGICAL RELEVANCE: Coix seed, the dry mature seed kernel of the gramineous plant coix (Coix lacryma-jobi L. var. ma-yuen Stapf), is widely consumed as a traditional Chinese medicine and functional food in China and South Korea. We have previously demonstrated the protective effect of coixol, a polyphenolic compound extracted from coix, against Toxoplasma gondii (T. gondii) infection-induced lung injury. However, the protective effect of coixol on hepatic injury induced by T. gondii infection have not yet been elucidated. AIM OF THE STUDY: This study explores the impact of coixol on T. gondii infection-induced liver injury and elucidates the underlying molecular mechanisms. MATERIALS AND METHODS: Female BALB/c mice and Kupffer cells (KCs) were employed to establish an acute T. gondii infection model in vivo and an inflammation model in vitro. The study examined coixol's influence on the T. gondii-derived heat shock protein 70 (T.g.HSP70)/toll-like receptor 4 (TLR4)/nuclear factor (NF)-κB signaling pathway in T. gondii-infected liver macrophages. Furthermore, a co-culture system of KCs and NCTC-1469 hepatocytes was developed to observe the impact of liver macrophages infected with T. gondii on hepatocyte injury. RESULTS: Coixol notably inhibited the proliferation of tachyzoites and the expression of T.g.HSP70 in mouse liver and KCs, and attenuated pathological liver injury. Moreover, coixol decreased the production of high mobility group box 1, tumor necrosis factor-α, and inducible nitric oxide synthase by suppressing the TLR4/NF-κB signaling pathway in vitro and in vivo. Coixol also mitigated KCs-mediated hepatocyte injury. CONCLUSIONS: Coixol protects against liver injury caused by T. gondii infection, potentially by diminishing hepatocyte injury through the suppression of the inflammatory cascade mediated by the T.g.HSP70/TLR4/NF-κB signaling pathway in KCs. These findings offer new perspectives for developing coixol as a lead compound for anti-T. gondii drugs.
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Tibetan strawberry (Fragaria nubicola) is a wild medicinal and edible plant in Tibet possessing various health benefits such as neuroprotection and anti-oxidation. However, there has been little study reported on its chemical constituents. To investigate the inhibitors of monoamine oxidase B (MAO-B) in Tibetan strawberry, we immobilized the enzyme onto cellulose filter paper for the first time to develop a new screening method. Two known glycosides (compounds 1 and 2) and one new iridoid glucoside (Compound 3) were fished out by this method, which was found to effectively inhibit MAO-B with IC50 values of 16.95 ± 0.93, 24.69 ± 0.20, and 46.77 ± 0.78 µM, respectively. Molecular docking and kinetic analysis were performed to reveal the inhibition mechanism of these compounds. Furthermore, compound 1 exhibited neuroprotective effects against 6-OHDA-induced injury on PC12 cells. The developed method exhibits the advantages of rapidness and effectiveness in screening of MAO-B inhibitors from complex herbal extracts.
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BACKGROUND: Infection by Toxoplasma gondii can lead to severe pneumonia, with current treatments being highly inadequate. The NLRP3 inflammasome is one member of the NOD-like receptor family with a pyrin domain, which is crucial in the innate immune defense against T. gondii. Research has shown that resveratrol (RSV) prevents lung damage caused by this infection by inhibiting the T. gondii-derived heat shock protein 70/TLR4/NF-κB pathway, thus reducing the macrophage-driven inflammatory response. However, it should be mentioned that the participation of NLRP3 inflammasome in the immune response to the lung injuries caused by T. gondii infections is not entirely clear. PURPOSE: This study aims to clarify how RSV ameliorates lung damage triggered by Toxoplasma gondii infection, with a particular focus on the pathway involving TLR4, NF-κB, and the NLRP3 inflammasome. METHODS: Both in vitro and in vivo models of infection were developed by employing the RH strain of T. gondii in BALB/c mice and RAW 264.7 macrophage cell lines. The action mechanism of RSV was explored using techniques such as molecular docking, surface plasmon resonance, ELISA, Western blot, co-immunoprecipitation, and immunofluorescence staining. RESULTS: Findings indicate that the suppression of TLR4 or NF-κB impacts the levels of proteins associated with the NLRP3 inflammasome pathway. Additionally, a significant affinity for binding between RSV and NLRP3 was observed. Treatment with RSV led to a marked reduction in the activation and formation of the NLRP3 inflammasome within lung tissues and RAW 264.7 cells, alongside a decrease in IL-1ß concentrations in the bronchoalveolar lavage fluid. These outcomes align with those seen when using the NLRP3 inhibitor CY-09. Moreover, the application of CY-09 prior to RSV negated the latter's anti-inflammatory properties. CONCLUSION: Considering insights from previous research alongside the outcomes of the current investigation, it appears that the TLR4/NF-κB/NLRP3 signaling pathway emerges as a promising target for immunomodulation to alleviate lung injury from T. gondii infection. The evidence gathered in this study lays the groundwork for the continued exploration and potential future clinical deployment of RSV as a therapeutic agent with anti-Toxoplasma properties and the capability to modulate the inflammatory response.
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Inflamassomos , Camundongos Endogâmicos BALB C , NF-kappa B , Proteína 3 que Contém Domínio de Pirina da Família NLR , Pneumonia , Resveratrol , Receptor 4 Toll-Like , Toxoplasma , Resveratrol/farmacologia , Animais , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Camundongos , Inflamassomos/efeitos dos fármacos , Inflamassomos/metabolismo , Células RAW 264.7 , Receptor 4 Toll-Like/metabolismo , Pneumonia/tratamento farmacológico , Pneumonia/parasitologia , Toxoplasma/efeitos dos fármacos , NF-kappa B/metabolismo , Toxoplasmose/tratamento farmacológico , Pulmão/efeitos dos fármacos , Pulmão/parasitologia , Simulação de Acoplamento Molecular , Feminino , Transdução de Sinais/efeitos dos fármacos , Macrófagos/efeitos dos fármacosRESUMO
OBJECTIVES: To evaluate the efficacy and safety of ringheaded thrumbtack needle in the treatment of allergic rhinitis (AR). METHODS: Clinical studies about treatment of AR with ringheaded thrumbtack needle were searched from databases of CNKI, Wanfang, China Science and Technology Journal, China Biology Medicine disc, PubMed, Embase and Web of Science from their inception to November 2022. Two researchers independently screened the literature and collected related information. The total effective rate, visual analogue scale (VAS) for AR, rhinoconjunctivitis quality of life questionnaire (RQLQ), and recurrence rate were the main outcome indicators. Secondary outcome indicators included quantitative scores of symptoms and signs, 'quartering' symptom evaluation scale, etc. All the included studies were subjected to Meta-analysis using Stata software. RESULTS: A total of 22 clinical studies involving 1 491 participants were included. The results of Meta-analysis indicated that the total effective rate of ringheaded thrumbtack needle in the treatment of AR was higher than that of traditional Chinese and Western medicine ï¼»RR=1.20, 95%CI (1.14, 1.26), P<0.001ï¼½, and recurrence rate is lower than conventional therapy ï¼»OR=0.35, 95%CI (0.14, 0.89), P=0.027ï¼½. Moreover, The VAS score ï¼»WMD=-1.30, 95%CI (-1.85, -0.75), P<0.001ï¼½ and RQLQ score ï¼»WMD=-6.75, 95%CI (-12.74, -0.76), P=0.027ï¼½ of AR treated by ringheaded thrumbtack needle were lower than those of traditional Chinese and Western medicine. CONCLUSIONS: Ringheaded thrumbtack needle can improve the total effective rate, reduce the disease recurrence, and improve the symptoms of discomfort when AR outbreaks, and has no significant adverse reactions. However, the reliability is limited. Thus, it is still necessary to improve the level of evidence quality by including researches with large samples, rigorous design and international standards.
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Terapia por Acupuntura , Agulhas , Rinite Alérgica , Humanos , Rinite Alérgica/terapia , Resultado do Tratamento , Pontos de Acupuntura , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Solid phase extraction (SPE) and liquid chromatographic (LC) separation of nucleobases and nucleosides are challenging due to the high hydrophilicity of these compounds. Herein we report a novel on-line SPE-LC-MS/MS method for their quantification after pre-column derivatization with chloroacetaldehyde (CAA). The method proposed is selective and sensitive with limits of detection at the nano-molar level. Analysis of urine and saliva samples by using this method is demonstrated. Adenine, guanine, cytosine, adenosine, guanosine, and cytidine were found in the range from 0.19 (guanosine) to 1.83 µM (cytidine) in urine and from 0.015 (guanosine) to 0.79 µM (adenine) in saliva. Interestingly, methylation of cytidine was found to be significantly different in urine from that in saliva. While 5-hydroxymethylcytidine was detected at a very low level (<0.05 µM) in saliva, it was found to be the most prominent methylated cytidine in urine at a high level of 3.33 µM. Since on-line SPE is deployed, the proposed LC-MS/MS quantitative assay is convenient to carry out and offers good assay accuracy and repeatability.
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Nucleosídeos , Saliva , Extração em Fase Sólida , Humanos , Limite de Detecção , Espectrometria de Massa com Cromatografia Líquida , Nucleosídeos/urina , Nucleosídeos/análise , Saliva/química , Extração em Fase Sólida/métodosRESUMO
Augmented CD4+ T cell response in autoimmunity is characterized by extensive metabolic reprogramming. However, the epigenetic molecule that drives the metabolic adaptation of CD4+ T cells remains largely unknown. Here, we show that lysine acetyltransferase 6A (KAT6A), an epigenetic modulator that is clinically associated with autoimmunity, orchestrates the metabolic reprogramming of glucose in CD4+ T cells. KAT6A is required for the proliferation and differentiation of proinflammatory CD4+ T cell subsets in vitro, and mice with KAT6A-deficient CD4+ T cells are less susceptible to experimental autoimmune encephalomyelitis and colitis. Mechanistically, KAT6A orchestrates the abundance of histone acetylation at the chromatin where several glycolytic genes are located, thus affecting glucose metabolic reprogramming and subsequent CD4+ T cell responses. Treatment with KAT6A small-molecule inhibitors in mouse models shows high therapeutic value for targeting KAT6A in autoimmunity. Our study provides novel insights into the epigenetic programming of immunometabolism and suggests potential therapeutic targets for patients with autoimmunity.
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Lisina Acetiltransferases , Linfócitos T , Animais , Humanos , Camundongos , Autoimunidade/genética , Linfócitos T CD4-Positivos/metabolismo , Epigênese Genética , Glucose/metabolismo , Histona Acetiltransferases/genética , Histona Acetiltransferases/metabolismo , Lisina Acetiltransferases/genética , Lisina Acetiltransferases/metabolismo , Linfócitos T/metabolismoRESUMO
Cancer stem cells (CSCs) are the most intractable subpopulation of triple-negative breast cancer (TNBC) cells, which have been associated with a high risk of relapse and poor prognosis. However, eradication of CSCs continues to be difficult. Here, we integrate the multiomics data of a TNBC cohort (n = 360) to identify vital markers of CSCs. We discover that EMSY, inducing a BRCAness phenotype, is preferentially expressed in breast CSCs, promotes ALDH+ cells enrichment, and is positively correlated with poor relapse-free survival. Mechanistically, EMSY competitively binds to the Jmjc domain, which is critical for KDM5B enzyme activity, to reshape methionine metabolism, and to promote CSC self-renewal and tumorigenesis in an H3K4 methylation-dependent manner. Moreover, EMSY accumulation in TNBC cells sensitizes them to PARP inhibitors against bulk cells and methionine deprivation against CSCs. These findings indicate that clinically relevant eradication of CSCs could be achieved with a strategy that targets CSC-specific vulnerabilities in amino acid metabolism.
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Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/metabolismo , Linhagem Celular Tumoral , Recidiva Local de NeoplasiaRESUMO
Perfluorooctanoic acid (PFOA) is a widely used industrial compound that has been found to induce intestinal toxicity. However, the underlying mechanisms have not been fully clarified and effective interventions are rarely developed. Inulin, a prebiotic, has been used as a supplement in human daily life as well as in gastrointestinal diseases and metabolic disorders. In this study, male mice were exposed to PFOA with or without inulin supplementation to investigate the enterotoxicity and potential intervention effects of inulin. Mice were administered PFOA at 1 mg/kg/day, PFOA with inulin at 5 g/kg/day, or Milli-Q water for 12 weeks. Histopathological analysis showed that PFOA caused colon shortening, goblet cell reduction, and inflammatory cell infiltration. The expression of the tight junction proteins ZO-1, occludin and claudin5 significantly decreased, indicating impaired barrier function. According to the RNA-sequencing analysis, PFOA exposure resulted in 917 differentially expressed genes, involving 39 significant pathways, such as TNF signaling and cell cycle pathways. In addition, the protein expression of TNF-α, IRG-47, cyclinB1, and cyclinB2 increased, while Gadd45γ, Lzip, and Jam2 decreased, suggesting the involvement of the TNF signaling pathway, cell cycle, and cell adhesion molecules in PFOA-associated intestinal injury. Inulin intervention alleviated PFOA-induced enterotoxicity by activating the PI3K/AKT/mTOR signaling pathway and increasing the protein expression of Wnt1, ß-catenin, PI3K, Akt3, and p62, while suppressing MAP LC3ß, TNF-α, and CyclinE expression. These findings suggested that PFOA-induced intestinal injury, including inflammation and tight junction disruption, was mitigated by inulin through modifying the PI3K/AKT/mTOR signaling pathways. Our study provides valuable insights into the enterotoxic effects of PFOA and highlights the potential therapeutic role of inulin.
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Caprilatos , Fluorocarbonos , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Humanos , Masculino , Camundongos , Animais , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Inulina/farmacologia , Fator de Necrose Tumoral alfa/metabolismo , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismoRESUMO
Background: Alpha-synuclein (SNCA) copy number variations (CNV) have been certified as a causative mutation in patients with familial and sporadic Parkinson's disease (PD). Case: We report three SNCA duplication cases diagnosed as PD. Through whole-exome sequencing, we identified a de novo 4.56 Mb repeated region in one patient and a 2.50 Mb repeated region in familial PD with two patients. Literature review: In review of previous cases, we suggest that aggressive behavior is more remarkable in CNV4 patients. Meanwhile, frequency of cognition decline and dementia were slightly increased in CNV4 patients. We also illustrate a younger onset age in offspring than parent in familial SNCA multiplication PD cases. No difference was observed in disease duration between parent and offspring generation. Conclusions: Our findings demonstrated the clinical and genetic characteristics in PD with SNCA multiplication and provided strong evidence for genetic anticipation. These results may be instructive for future disease diagnosis and genetic counseling.
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Activation of inflammasomes-immune system receptor sensor complexes that selectively activate inflammatory responses-has been associated with diverse human diseases, and many nanomedicine studies have reported that structurally and chemically diverse inorganic nanomaterials cause excessive inflammasome activation. Here, in stark contrast to reports of other inorganic nanomaterials, we find that nickel-cobalt alloy magnetic nanocrystals (NiCo NCs) actually inhibit activation of NLRP3, NLRC4 and AIM2 inflammasomes. We show that NiCo NCs disrupt the canonical inflammasome ASC speck formation process by downregulating the lncRNA Neat1, and experimentally confirm that the entry of NiCo NCs into cells is required for the observed inhibition of inflammasome activation. Furthermore, we find that NiCo NCs inhibit neutrophil recruitment in an acute peritonitis mouse model and relieve symptoms in a colitis mouse model, again by inhibiting inflammasome activation. Beyond demonstrating a highly surprising and apparently therapeutic impact for an inorganic nanomaterial on inflammatory responses, our work suggests that nickel- and cobalt-containing nanomaterials may offer an opportunity to design anti-inflammatory nanomedicines for the therapeutics of macrophage-mediated diseases.
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BACKGROUND: Endoscopy has rapidly developed in recent years and has enabled further investigation into the origin and features of intestinal tumors. The small size and concealed position of these tumors make it difficult to distinguish them from nonneoplastic polyps and carcinoma in adenoma (CIA). The invasive depth and metastatic potential determine the operation regimen, which in turn affects the overall survival and distant prognosis. The previous studies have confirmed the malignant features and clinicopathological features of de novo colorectal cancer (CRC). AIM: To provide assistance for diagnosis and treatment, but the lack of a summary of endoscopic features and assessment of risk factors that differ from the CIA prompted us to conduct this retrospective study. METHODS: In total, 167 patients with small-sized CRCs diagnosed by endoscopy were reviewed. The patients diagnosed as advanced CRCs and other malignant cancers or chronic diseases that could affect distant outcomes were excluded. After screening, 63 cases were excluded, including 33 de novo and 30 CIA cases. Patient information, including their follow-up information, was obtained from an electronic His-system. The characteristics between two group and risk factors for invasion depth were analyzed with SPSS 25.0 software. RESULTS: Nearly half of the de novo CRCs were smaller than 1 cm (n = 16, 48.5%) and the majority were located in the distal colon (n = 26, 78.8%). The IIc type was the most common macroscopic type of de novo CRC. In a Pearson analysis, the differential degree, Sano, JNET, and Kudo types, surrounding mucosa, and chicken skin mucosa (CSM) were correlated with the invasion depth (P < 0.001). CSM was a significant risk factor for deep invasion and disturbed judgment of endoscopic ultrasound. A high degree of tumor budding and tumor-infiltrating lymphocytes are accompanied by malignancy. Finally, de novo CRCs have worse outcomes than CIA CRCs. CONCLUSION: This is the first comprehensive study to analyze the features of de novo CRCs to distinguish them from nonneoplastic polyps. It is also the first study paying attention to CSM invasive depth measurement. This study emphasizes the high metastatic potential of de novo CRCs and highlights the need for more research on this tumor type.
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Adenoma , Neoplasias Colorretais , Humanos , Estudos Retrospectivos , Neoplasias Colorretais/patologia , Endoscopia , Fatores de Risco , Adenoma/diagnóstico por imagem , Adenoma/cirurgiaRESUMO
The begomovirus-betasatellite complex constantly threatens crops in Asia. However, the quantitative relationship between begomoviruses and betasatellites remains largely unknown. The quantities of tobacco curly shoot virus (TbCSV) and its betasatellite (TbCSB) and their ratio varied significantly in initial infection, and thereafter, the ratio tended to become constant. The TbCSB/TbCSV ratio in agrobacteria inoculum significantly affected that in plants in the initial infection but not thereafter. Null-mutation of ßC1 that encodes a multifunctional protein important for pathogenesis in TbCSB significantly reduced the TbCSB/TbCSV ratio in plants. Viral inoculum plants with higher TbCSB/TbCSV ratios promoted whitefly transmission of the virus. The expression of AV1 encoded by TbCSV, ßC1 encoded by TbCSB and the ßC1/AV1 ratio varied significantly in the initial infection and thereafter the ratio tended to become constant. Additionally, the temporal dynamics of the ratio between another begomovirus and its betasatellite was similar to that of TbCSV and was positively regulated by ßC1. These results indicate that the ratio between monopartite begomoviruses and betasatellites tend to become constant as infection progresses, and is modulated by ßC1, but a higher betasatellite/begomovirus ratio in virally inoculated plants promotes virus transmission by whiteflies. Our findings provide novel insights into the association between begomoviruses and betasatellites.
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Begomovirus , Begomovirus/genética , Nicotiana , Genes Virais , Ásia , Doenças das Plantas , DNA Viral/genéticaRESUMO
DNA methylation is intensively studied in medical science. Current HPLC methods for quantification of global DNA methylation involve digestion of a DNA sample and HPLC determination of both cytosine (C) and 5-methylcytosine (5mC) so that percentage of 5mC in total cytosine can be calculated as DNA methylation level. Herein we report a novel HPLC method based on a one-pot fluorescence tagging and depyrimidination reaction between DNA and chloroacetaldehyde (CAA) for highly sensitive quantification of global DNA methylation. In the one-pot reaction, C and 5mC residues in a DNA sequence react with CAA, forming fluorescent etheno-adducts that are then released from the sequence through depyrimidination. Interestingly, etheno-5mC (ε-5mC) is â¼20 times more fluorescent than ε-C and other ε-nucleobases resulting from the reaction, which greatly facilitates the quantification. Further, due to the tagging-induced increase in structural aromaticity, ε-nucleobases are far more separable by HPLC than intact nucleobases. The proposed HPLC method with fluorescence detection (HPLC-FD) is quick (i.e., < 1h per assay) and highly sensitive with a detection limit of 0.80 nM (or 250 fg on column) for 5mC. Using the method, DNA samples isolated from yeast, HCT-116 cells, and tissues were analyzed. Global DNA methylation was measured to be in the range from 0.35% to 2.23% in the samples analyzed. This sensitive method allowed accurate analyses of minute DNA samples (â¼100 ng) isolated from milligrams of tissues.
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5-Metilcitosina , Metilação de DNA , 5-Metilcitosina/análise , Citosina , Cromatografia Líquida de Alta Pressão/métodos , DNA/análiseRESUMO
Breast cancer is now the most frequently diagnosed malignancy, and metastasis remains the leading cause of death in breast cancer. However, little is known about the dynamic changes during the evolvement of dissemination. In this study, 65 968 cells from four patients with breast cancer and paired metastatic axillary lymph nodes are profiled using single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics. A disseminated cancer cell cluster with high levels of oxidative phosphorylation (OXPHOS), including the upregulation of cytochrome C oxidase subunit 6C and dehydrogenase/reductase 2, is identified. The transition between glycolysis and OXPHOS when dissemination initiates is noticed. Furthermore, this distinct cell cluster is distributed along the tumor's leading edge. The findings here are verified in three different cohorts of breast cancer patients and an external scRNA-seq dataset, which includes eight patients with breast cancer and paired metastatic axillary lymph nodes. This work describes the dynamic metabolic evolvement of early disseminated breast cancer and reveals a switch between glycolysis and OXPHOS in breast cancer cells as the early event during lymph node metastasis.
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Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/metabolismo , Transcriptoma/genética , Metástase Linfática/genética , Metástase Linfática/patologia , Glicólise/genética , LinfonodosRESUMO
Fragaria nubicola, known as Tibetan strawberry, is an edible plant possessing various health-promoting effects. However, its functional compositions were rarely studied. In this work, monoamine oxidase B (MAO-B) inhibitors in this plant were rapidly screened using the enzyme-functionalized magnetic nanoparticles coupled with UPLC-QTOF-MS. Two inhibitors, quercetin-3-O-ß-d-glucuronide-6â³-methyl ester (1) and kaempferol-3-O-ß-d-glucuronide-6â³-methyl ester (2), were identified from this plant with the IC50 values of 19.44 ± 1.17 and 22.63 ± 1.78 µM, respectively. Enzyme kinetic analysis and molecular docking were carried out to investigate the mechanism of inhibition. Contents of both compounds as well as those of total phenolics and flavonoids were quantified to be 24.76 ± 1.26, 35.59 ± 1.17, 837.67 ± 10.62, and 593.46 ± 10.37 µg/g, respectively. In addition, both compounds exhibited significant neuroprotective effects on 6-hydroxydopamine-induced PC12 cells. This is the first report on the neuroprotective components of F. nubicola, suggesting its potential for developing neuroprotective functional food.
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Fragaria , Fármacos Neuroprotetores , Animais , Ratos , Fragaria/metabolismo , Glucuronídeos , Cinética , Ligantes , Simulação de Acoplamento Molecular , Monoaminoxidase/metabolismo , Inibidores da Monoaminoxidase/farmacologia , Fármacos Neuroprotetores/farmacologia , Extratos Vegetais/farmacologia , Extratos Vegetais/análise , Relação Estrutura-AtividadeRESUMO
Clinical, laboratory, and microbiological features, clinical outcomes, and pyogenic liver abscess (PLA) prognosis evaluation in non-liver cancer (Non-LC) and liver cancer patients treated with transarterial chemoembolization (TACE, LC-TACE). Clinical data of 48 consecutive PLA patients from January 2016 to December 2020 were retrospectively analyzed. Mortality between two PLA patient groups were compared, and mortality risk factors were evaluated. A total of 48 PLA patients (31 males and 17 females) from January 2016 to December 2020 met the study's inclusion criteria. There were 32 and 16 patients in the Non-LC and LC-TACE groups, respectively. Positive pus culture rate in the Non-LC group was 87.5% and positive pus culture rate in LC-TACE group was 81.3%. In the Non-LC group, 28 patients improved after treatment, 1 patient did not improve, and 3 patients died during hospitalization, with a 9.4% mortality rate. In the LC-TACE group, nine patients improved after treatment, three patients did not improve, and four patients died during hospitalization, with a 25% mortality rate. The Non-LC group cure time was 37.4 ± 23.1 days, while the LC-TACE group was 91.5 ± 49.7 days. PLA of the Non-LC group and the LC-TACE group were different in terms of pathogenic bacteria and cure time, and so on. A more comprehensive treatment should be considered for PLA after TACE.
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Carcinoma Hepatocelular , Quimioembolização Terapêutica , Abscesso Hepático Piogênico , Neoplasias Hepáticas , Masculino , Feminino , Humanos , Abscesso Hepático Piogênico/terapia , Abscesso Hepático Piogênico/microbiologia , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/etiologia , Estudos Retrospectivos , Neoplasias Hepáticas/patologia , Quimioembolização Terapêutica/efeitos adversos , Resultado do TratamentoRESUMO
Introduction: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is effective for the treatment of Parkinson's disease (PD). Moreover, remote programming is widely used in Mainland China. This necessitates evaluating the ability of remote programming to achieve the ideal postoperative effect. Therefore, we aimed to retrospectively evaluate the effects of different programming modes on the effectiveness of STN-DBS 12 months postoperatively in patients with PD. Methods: Clinical data were collected retrospectively, before and 12 months after surgery, in 83 patients with PD. Based on the programming modes voluntarily selected by the patients during 12 months postoperatively, they were divided into three groups, namely remote programming alone, hospital programming alone, and hospital + remote programming. We compared the programming data and the effects of different programming methods on STN-DBS-related improvements 12 months postoperatively among these groups. Furthermore, we analyzed STN-DBS-related improvements at 12 months postoperatively in 76 patients. Results: The effectiveness of STN-DBS was not influenced by the three programming modes. The postoperative Movement Disorder Society Unified Parkinson's Disease Rating Scale scores did not reveal statistically significant differences between the remote alone and hospital alone programming groups, except for motor examination. The postoperative decline in the levodopa equivalent daily dose was most apparent in the hospital programming alone group. The programming frequency of the hospital + remote programming group was considerably higher than that of the remaining groups. Seventy-six patients with PD displayed good STN-DBS surgical efficacy. Conclusion: Programming modes do not influence the short-term efficacy of STN-DBS, and remote programming can yield a satisfactory surgical effect.
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AIM: To evaluate the efficacy and safety of HLX04-O, an investigational ophthalmic formulation of HLX04 (bevacizumab biosimilar) for intravitreal injection, as a treatment for wet age-related macular degeneration (wAMD) in a phase 1/2 clinical trial (NCT04993352). METHODS: Eligible patients with wAMD were enrolled to receive HLX04-O intravitreal injections at a dose of 1.25 mg/0.05 mL every four weeks. Efficacy and adverse events were evaluated every month during study visits. RESULTS: A 76-year-old male with wAMD in his left eye participated in the trial and completed six cycles of HLX04-O intravitreal injections. Changes were observed in macular center point thickness (baseline vs last study visit, 437 vs 255 µm) and best-corrected visual acuity letter score (baseline vs last study visit, 36 vs 77) of the affected eye, which indicated an improvement in wAMD over treatment. No adverse events were reported by the data cutoff date. CONCLUSION: HLX04-O at 1.25 mg/0.05 mL every four weeks is well tolerated in this patient, demonstrating promising safety and efficacy in wAMD treatment. Large-scale studies are required to confirm the outcomes.
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A 69-year-old male patient was admitted by 10 h severe chest pain. Computed tomography angiography showed a 7.3 cm aneurysm of the aortic arch. We used a three-dimensional parametric surface planar topological guide plate to prepare a guide plate in 40 min. The plate was used to localize the opening of the aortic arch branches on table to create a physician-modified stent graft (PMSG). The aneurysm was successfully repaired by the triple inner branched PMSG, with no endoleak and all the branched arteries patency in follow-up. This technique could not only make accurate fenestration but also meet the need for emergency surgery.