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Colorectal cancer (CRC) is a prevalent malignancy with high mortality rates and poor prognosis. Shikonin (SHK) has demonstrated extensive anti-tumor activity across various cancers, yet its clinical application is hindered by poor solubility, limited bioavailability, and high toxicity. This study aims to develop SHK-loaded exosomes (SHK-Exos) and assess their efficacy in CRC progression. Exosomes were isolated using ultracentrifugation and characterized via TEM, NTA, and western blotting. Their cellular internalization was confirmed through confocal microscopy post PKH67 labeling. Effects on cell behaviors were assessed using CCK-8 and Transwell assays. Cell cycle and apoptosis were analyzed via flow cytometry. A xenograft tumor model evaluatedin vivotherapeutic potential, and tumor tissues were examined using H&E staining andin vivoimaging. SHK-Exos demonstrated effective cell targeting and internalization in CRC cells.In vitro, SHK-Exos surpassed free SHK in inhibiting aggressive cellular behaviors and promoting apoptosis, whilein vivostudies showed substantial efficacy in reducing tumor growth with excellent tumor targeting and minimal toxicity. Employing SHK-Exos effectively impedes CRC progressionin vitroandin vivo, offering significant therapeutic potential. This research underscores the advantages of using autologous exosomes as a drug carrier, enhancing efficacy and reducing toxicity.
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Apoptose , Neoplasias Colorretais , Exossomos , Naftoquinonas , Naftoquinonas/farmacologia , Naftoquinonas/química , Exossomos/metabolismo , Exossomos/efeitos dos fármacos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Neoplasias Colorretais/metabolismo , Humanos , Animais , Apoptose/efeitos dos fármacos , Camundongos , Linhagem Celular Tumoral , Camundongos Nus , Ensaios Antitumorais Modelo de Xenoenxerto , Progressão da Doença , Camundongos Endogâmicos BALB C , Proliferação de Células/efeitos dos fármacos , Portadores de Fármacos/química , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/uso terapêuticoRESUMO
INTRODUCTION: The objective of this research was to study the factors associated with the alveolar bone depth mesial to the mandibular third molars (M8) after the mandibular second (M7) and third molars were protracted into the space of the mandibular first molars (M6), which were newly extracted for orthodontic treatment or extracted more than 1 year before treatment. METHODS: This retrospective study included 57 adult patients (mean age 23.40 ± 4.40 years) in whom M6 were newly extracted for orthodontic treatment or extracted more than 1 year before treatment. The alveolar bone depth mesial to M8 was measured on posttreatment panoramic radiographs. The vertical, horizontal, and angular changes of M8 were measured on both pre- and posttreatment panoramic radiographs. Linear correlation and regression analyses were conducted to explore the factors associated with the alveolar bone depth mesial to M8. RESULTS: The alveolar bone conditions of M6 (R= -0.391, P <0.001) and the vertical movement directions of M8 (R= -0.433, P <0.001) were significant factors associated with the alveolar bone depth mesial to M8 after orthodontic protraction. CONCLUSIONS: Without considering the pretreatment periodontal status of M8, patients with M6 extracted exceeding 1 year before treatment and with M8 extruded after orthodontic protraction may exhibit deeper alveolar bone depth mesial to M8.
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Dente Serotino , Dente Molar , Adulto , Humanos , Mandíbula/diagnóstico por imagem , Dente Serotino/diagnóstico por imagem , Radiografia Panorâmica , Estudos Retrospectivos , Adulto JovemRESUMO
The construction of hydrophobic nanochannel with hydrophilic sites for bionic devices to proximally mimick real bio-system is still challenging. Taking the advantages of MOF chemistry, a highly oriented CuTCPP thin film has been successfully reconstructed with ultra-thin nanosheets to produce abundant two-dimensional interstitial hydrophobic nanochannels with hydrophilic sites. Different from the classical active-layer material with proton transport in bulk, CuTCPP thin film represents a new type of active-layer with proton transport in nanochannel for bionic proton field-effect transistor (H+ -FETs). The resultant device can reversibly modulate the proton transport by varying the voltage on its gate electrode. Meanwhile, it shows the highest proton mobility of ≈9.5×10-3 â cm2 V-1 s-1 and highest on-off ratio of 4.1 among all of the reported H+ -FETs. Our result demonstrates a powerful material design strategy for proximally mimicking the structure and properties of bio-systems and constructing bionic electrical devices.
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ETHNOPHARMACOLOGICAL RELEVANCE: Sleep problems, according to Traditional Chinese medicine (TCM) philosophy, are attributed to the imbalance between yin and yang. Zhumian Granules, also known as Sleep-aid Granules or ZG, are a traditional Chinese herbal remedy specifically designed to alleviate insomnia. This formula consists of many components, including Wu Wei Zi (Schisandrae Chinensis Fructus), Suan Zao Ren (Ziziphi Spinosae Semen), and other medicinal plants. According to the pharmacology of Traditional Chinese Medicine (TCM), Wu Wei Zi and Suan Zao Ren have the ability to relax the mind and promote sleep. When taken together, they may balance the opposing forces of yin and yang. Therefore, ZG may potentially be used as a therapeutic treatment for insomnia. AIM OF THE STUDY: This research was specifically developed to establish a strong empirical basis for the subsequent advancement and utilization of ZG in the management of insomnia. This research aimed to gather empirical data to support the effectiveness of ZG, thereby providing useful insights into its potential therapeutic advantages for persons with insomnia. MATERIALS AND METHODS: This study utilized Zhumian Granules (ZG), a traditional Chinese herbal decoction, to examine its sedative and hypnotic effects on mice with PCPA-induced insomnia. The effects were assessed using the pentobarbital-induced sleep test (PIST), Morris water maze test (MWM), and autonomic activity test. The levels of neurotransmitters in each group of mice were evaluated using UPLC-QQQ-MS. The impact of ZG on the quantity and structure of hippocampal neurons was seen in brain tissue slices using immunofluorescence labeling. RESULTS: ZG was shown to possess active sedative properties, effectively lowering the distance of movement and lengthening the duration of sleep. ZG mitigated the sleeplessness effects of PCPA by elevating the levels of 5-hydroxytryptamine (5-HT), 4-aminobutyric acid (GABA), and 5-hydroxyindoleacetic acid (5-HIAA), while reducing the levels of dopamine (DA) and norepinephrine (NE), as well as decreasing neuronal death. CONCLUSIONS: This research confirmed the sedative and hypnotic properties of ZG and elucidated its probable mechanism involving neurotransmitters.
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Schisandra , Distúrbios do Início e da Manutenção do Sono , Camundongos , Animais , Distúrbios do Início e da Manutenção do Sono/induzido quimicamente , Distúrbios do Início e da Manutenção do Sono/tratamento farmacológico , Medicina Tradicional Chinesa , Hipnóticos e Sedativos/farmacologia , Ácido gama-Aminobutírico , Serotonina , Neurotransmissores , ApoptoseRESUMO
BACKGROUND: Colon cancer (CC) is the most frequently occurring digestive system malignancy and is associated with a dismal prognosis. While super-enhancer (SE) genes have been identified as prognostic markers in several cancers, their potential as practical prognostic markers for CC patients remains unexplored. METHODS: We obtained super-enhancer-related genes (SERGs) from the Human Super-Enhancer Database (SEdb). Transcriptome and relevant clinical data for colon cancer (CC) were sourced from the Gene Expression Omnibus (GEO) database. Subsequently, we identified up-regulated SERGs by the Weighted Gene Co-expression Network Analysis (WGCNA). Prognostic signatures were constructed via univariate and multivariate Cox regression analysis. We then delved into the mechanisms of these predictive genes by examining immune infiltration. We also assessed differential sensitivities to chemotherapeutic drugs between high- and low-SERGs risk patients. The critical gene was further validated using external datasets and finally confirmed by qRT PCR. RESULTS: We established a ten-gene risk score prognostic model (S100A11, LZTS2, CYP2S1, ZNF552, PSMG1, GJC1, NXN, and DCBLD2), which can effectively predict patient survival rates. This model demonstrated effective prediction capabilities in survival rates at 1, 3, and 5 years and was successfully validated using external datasets. Furthermore, we detected significant differences in immune cell infiltration between high- and low-SERGs risk groups. Notably, high-risk patients exhibited heightened sensitivity to four chemotherapeutic agents, suggesting potential benefits for precision therapy in CC patients. Finally, qRT-PCR validation revealed a significant upregulation of LZTS2 mRNA expression in CC cells. CONCLUSION: These findings reveal that the SERGs model could effectively predict the prognosis of CC.
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Biomarcadores Tumorais , Neoplasias do Colo , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias do Colo/genética , Neoplasias do Colo/mortalidade , Neoplasias do Colo/patologia , Prognóstico , Biomarcadores Tumorais/genética , Transcriptoma , Bases de Dados Genéticas , Perfilação da Expressão Gênica , Feminino , Redes Reguladoras de GenesRESUMO
Paotianxiong (PTX) is a processing product of Aconitum carmichaelii Debx., often used as a tonic food daily. However, the structure and activity of the polysaccharide component that plays a major role still need to be determined. In our work, two new polysaccharides were purified from PTX and named PTXP-1 and PTXP-2. Structural analysis showed that PTXP-1 is a glucan with a molecular weight of 915 Da and a structure of 4)-α-D-Glcp-(1 â as the main chain. PTXP-2 is a glucose arabinoglycan with 4)-α-D-Glcp-(1 â as the main chain, containing 8 glycosidic bonds attached, and a molecular weight of 57.9KDa. In vitro probiotic experiments demonstrated that PTXP-1 could significantly promote probiotic growth and acid production. In vivo experiments demonstrated that both PTXP-1 and PTXP-2 exhibited significant effectiveness in promoting the growth of intestinal probiotics. These findings help expand the application of polysaccharide components extracted from tonic herbs as functional food ingredients.
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Polissacarídeos , Prebióticos , Probióticos , Prebióticos/análise , Polissacarídeos/química , Animais , Probióticos/química , Camundongos , Peso Molecular , Humanos , Masculino , Extratos Vegetais/químicaRESUMO
Colorectal cancer (CRC) ranks as the third most frequently diagnosed cancer and the fourth leading cause of cancer-related mortality worldwide. Treatment options for patients with advanced CRC recurrence and metastases remain limited, particularly for those unable to withstand chemotherapy. Bruscea javanica oil emulsion (BJOE) and Aidi injection (ADI) are two plant-derived products that have antitumor effects. The current report presents the case of a patient with colon cancer and resectable lung metastases. Despite the surgical removal of the metastatic lesions, tumor recurrence was not prevented. The patient underwent three chemotherapy regimens following lung metastasis surgery, namely XELOX, single-agent irinotecan and single-agent tegafur-gimeracil-oteracil potassium capsule, but experienced intolerable adverse reactions with each, and disease progression was observed during subsequent follow-up. Nonetheless, the patient achieved a progression-free survival of >5 years under BJOE + ADI treatment and continues to receive BJOE + ADI treatment to date. Although further research is required to understand the effectiveness of this treatment combination, the present case may instill hope in the treatment of future patients.
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Malignant pleural mesothelioma (MPM) is a severe form of cancer that originates from mesothelium cells. Around 54-90% of mesotheliomas are associated with pleural effusions. Brucea Javanica Oil Emulsion (BJOE) is the processed oil derived from the seeds of Brucea javanica, which has shown potential as a treatment option for several types of cancer. Here, we present a case study of a MPM patient with malignant pleural effusion who received intrapleural injection of BJOE. The treatment resulted in the complete response of pleural effusion and chest tightness. While the precise mechanisms underlying the therapeutic effects of BJOE for pleural effusion are not yet fully understood, it has demonstrated a satisfactory clinical response without significant adverse effects.
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Brucea , Mesotelioma Maligno , Mesotelioma , Derrame Pleural Maligno , Humanos , Brucea javanica , Emulsões/uso terapêutico , Mesotelioma/complicações , Mesotelioma/tratamento farmacológico , Óleos de Plantas/uso terapêutico , Derrame Pleural Maligno/tratamento farmacológico , Derrame Pleural Maligno/patologiaRESUMO
The development of low carbon treatment processes is an important issue worldwide. Partial denitrification coupled with anammox (PD/A) is a novel strategy to remove nitrogen and reduce N2O emissions. The influence of C/N ratio and NH4+ concentration on nitrogen removal and N2O emissions was investigated in batch reactors filled with PD/A coupled sludge. A C/N ratio of 2.1 was effective for nitrogen removal and N2O reduction; higher ammonia concentration might make anammox more active and indirectly reduce N2O emissions. Long-term operation further confirmed that a C/N ratio of 2.1 resulted in a minimum effluent N2O concentration (mean value of 0.94 µmol L-1); as the influent NH4+ concentration decreased to 50 mg L-1 (NH4+-N/NO3--N: 1), the nitrogen removal rate increased to 82.41%. Microbial analysis showed that anammox bacteria (Candidatus Jettenia and Ca. Brocadia) were enriched in the PD/A system and Ca. Brocadia gradually dominated the anammox community, with the relative abundance increasing from 1.69% to 18.44% between days 97 and 141. Finally, functional gene analysis indicated that the abundance of nirS/K and hao involved in partial denitrification and anammox, respectively, increased during long-term operation of the reactor; this change benefitted nitrogen metabolism in anammox, which could indirectly reduce N2O emissions.
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Amônia , Desnitrificação , Oxidação Anaeróbia da Amônia , Carbono , NitrogênioRESUMO
Objective: Peri-implantitis (PI) is one of the main reasons for dental implant failure. Until now, the etiology and pathogenesis of PI remain unclear. Methods: In this study, we used differentially expressed genes (DEGs) analysis and gene function enrichment analysis to assess the expression profile of peri-implant bone tissue and gingiva in PI public data from the Gene Expression Omnibus (GEO) database. Then, we used gingival tissues from patients with PI and healthy individual to construct gene coexpression networks to reveal the biological functions of the genes in PI using RNA sequencing data. Afterward, key gene modules were selected to reveal the critical biological process or signaling pathway using Hallmark's gene enrichment and expression analysis of the related pathway members in PI. Results: DEGs were enriched in the formation of cellular responses to external stimuli in bone tissue. Cytokine production, lymphocyte activation, immune response-regulating signaling pathway, and blood vessel development were the top GO biology process or pathways of the DEGs in gingival tissue. Weighted gene coexpression network analysis (WGCNA) of RNA-seq data was used to assess the results of correlation analysis between modules and traits and correlation analysis between modules and functions. kMEpurple, kMEgreen, and kMEred modules were selected as the key gene modules. Signaling pathways and gene expression analysis were performed on selected modules, such as IL2/STAT5 signaling pathway, TNFα signaling pathway via NFκB, and angiogenesis were enriched in kMEpurple module. Hedgehog signaling pathway, Wnt ß-catenin signaling pathway, and IL2/STAT5 signaling pathway were enriched in kMEgreen module. Peroxisome, IL2/STAT5 signaling pathway, and epithelial-mesenchymal transformation process were enriched in kMEred module. All the enrichment results of key modules contained IL2/STAT5 signaling pathway. Conclusion. Differential gene and enrichment analysis based on public data showed differences in gene expression patterns and biological process between bone and gingival tissues in PI. This spatial-temporal heterogeneity is reflected in the formation of cellular responses to external stimuli, which was enriched in bone tissue, but cytokine production, lymphocyte activation, immune response regulating signaling pathway, and blood vessel development were enriched in gingival tissue. WGCNA and Hallmark gene sets enrichment analysis of the gingival tissue expression profile and showed that IL2-mediated activation of immune cells could be a critical mechanism in PI. As a new clinical treatment alternative, we suggest that IL2/STAT5 pathway blockers could be helpful in the treatment of PI.
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Implantes Dentários , Peri-Implantite , Perfilação da Expressão Gênica/métodos , Redes Reguladoras de Genes , Proteínas Hedgehog/genética , Humanos , Interleucina-2/genética , Peri-Implantite/genética , Fator de Transcrição STAT5/genética , Transdução de Sinais/genética , Fator de Necrose Tumoral alfaRESUMO
Learning and memory impairment is a common clinical symptom of aging and nervous system injuries, and seriously affects quality of life. Memory impairment is associated with increased oxidative stress (OS) and inflammatory response. ß-hydroxybutyrate (BHBA) is a water-soluble endogenous small-molecule ketone body that easily crosses the blood-brain barrier and has shown neuroprotection activities. In this study, we investigated the effects and mechanisms of BHBA on D-galactose (D-gal)-induced memory impairment in mice by in vitro and in vivo experiments. BHBA was administered intragastrically to D-gal-injured C57BL/6 mice for 42 days. Water maze performance, the morphology of the hippocampus with Nissl staining, the ACh content, OS, and inflammation status were examined. To further investigate the mechanism, hippocampal neuronal cells (HT22) were treated with BHBA with or without the SIRT1 inhibitor or small interfering RNAs against sirt1 (si-SIRT1) before incubation with D-gal. BHBA significantly improved water maze performance; increased the ACh content, SOD activity, and SIRT1 expression; and decreased AChE and LDH activity, ROS, MDA, IL-1ß, TNF-α contents, and NLRP3 expression. Further studies with the SIRT inhibitor or siRNAs against sirt1 reversed the above effects of BHBA. Collectively, BHBA inhibited hippocampal OS and the inflammation process to alleviate learning and memory impairment through activating the SIRT1 pathway in D-gal-injured mice, suggesting that BHBA could be a potential option for drug development of learning and memory impairment induced by nervous system injuries.
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BACKGROUND AND OBJECTIVE: Although periimplantitis and periodontitis share similar features, particularly clinical features, they are two different diseases and should be analyzed separately. Thus far, few omics-level differences in periimplantitis and periodontitis have been reported. This study was aimed at exploring the differential effects of expression mRNAs, lncRNAs, and miRNAs in periodontitis and periimplantitis by high-throughput sequencing and competitive endogenous RNA (ceRNA) analysis. METHODS: Gingival tissues of healthy individuals (HI) and periimplantitis (PI) and periodontitis (P) patients were collected and used for genome-wide sequencing. The differentially expressed genes (DEGs) were screened and visualized by R software. The functions and pathways of DEGs were analyzed using Metascape, and the ceRNA network was constructed using the Cytoscape software. Finally, gene set enrichment analysis (GSEA) was used to predict the function of key nodes in ceRNA. RESULTS AND CONCLUSION: By constructing the regulated ceRNA network, six genes (FAM126B, SORL1, PRLR, CPEB2, RAP2C, and YOD1) and 16 miRNAs (hsa-miR-338-5p, hsa-miR-650, hsa-miR-9-5p, hsa-miR-1290, hsa-miR-544a, hsa-miR-3179, hsa-miR-1269a, hsa-miR-3679-5p, hsa-miR-149-5p, hsa-miR-615-3p, hsa-miR-33b-5p, hsa-miR-31-5p, hsa-miR-4639-5p, hsa-miR-204-5p, hsa-miR-5588-5p, and hsa-mir-196a-5p) were detected. Five long non-coding RNAs (lnc-CORO2B-1, lnc-MBL2-7, lnc-TRIM45-1, lnc-CHST10-2, and lnc-TNP1-6) were found to target these miRNAs in this ceRNA network. The ceRNA network based on transcriptome data revealed that FAM126B, SORL1, PRLR, CPEB2, RAP2C, and YOD1 were crucial proteins of differential effects in periodontitis and periimplantitis. The lncRNA-miRNA-mRNA interaction involved the regulation of the Hippo signaling pathway, Wnt signaling pathway, Toll-like receptor signaling pathway, NOD signaling pathway, oxidative stress, and innate immune process. These regulated pathways and biological processes may be factors contributing to the pathogenesis of periimplantitis being distinct from that of periodontitis.
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Peri-Implantite , Periodontite , RNA Longo não Codificante , Endopeptidases , Humanos , Proteínas dos Microfilamentos , RNA Mensageiro , Proteínas de Ligação a RNA , Proteínas Repressoras , Tioléster Hidrolases , Transcriptoma , Proteínas rasRESUMO
Saccharides from Arctium lappa. L. root (ALR-S) is a high-purity fructosaccharide separated from the medicinal plant Arctium lappa. L. root. These compounds showed many pharmacological effects in previous studies. In the present study, the antithrombotic effects of ALR-S in arterial thrombosis via inhibiting platelet adhesion and rebalancing thrombotic and antithrombotic factor expression and secretion were found in rats and human aortic endothelial cells (HAECs). This study also showed that inhibition of oxidative stress (OS), which is closely involved in the expression of coagulation- and thrombosis-related proteins, was involved in the antithrombotic effects of ALR-S. Furthermore, studies using FeCl3-treated HAECs showed that ALR-S induced the abovementioned effects at least partly by blocking the ERK/NF-κB pathway. Moreover, U0126, a specific inhibitor of ERK, exhibited the same effects with ALR-S on a thrombotic process in FeCl3-injured HAECs, suggesting the thrombotic role of the ERK/NF-κB pathway and the antithrombotic role of blocking the ERK/NF-κB pathway by ALR-S. In conclusion, our study revealed that the ERK/NF-κB pathway is a potential therapeutic target in arterial thrombosis and that ALR-S has good characteristics for the cure of arterial thrombosis via regulating the ERK/NF-κB signaling pathway.
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Arctium/química , Sistema de Sinalização das MAP Quinases/fisiologia , NF-kappa B/metabolismo , Raízes de Plantas/química , Plantas Medicinais/química , Animais , Humanos , Masculino , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , TromboseRESUMO
The triply periodic minimal surface (TPMS) method is a novel approach for lattice design in a range of fields, such as impact protection and structural lightweighting. In this paper, we used the TPMS formula to rapidly and accurately generate the most common lattice structure, named the body centered cubic (BCC) structure, with certain volume fractions. TPMS-based and computer aided design (CAD) based BCC lattice structures with volume fractions in the range of 10â»30% were fabricated by selective laser melting (SLM) technology with Tiâ»6Alâ»4V and subjected to compressive tests. The results demonstrated that local geometric features changed the volume and stress distributions, revealing that the TPMS-based samples were superior to the CAD-based ones, with elastic modulus, yield strength and compression strength increasing in the ranges of 18.9â»42.2%, 19.2â»29.5%, and 2â»36.6%, respectively. The failure mechanism of the TPMS-based samples with a high volume fraction changed to brittle failure observed by scanning electron microscope (SEM), as their struts were more affected by the axial force and fractured on struts. It was also found that the TPMS-based samples have a favorable capacity to absorb energy, particularly with a 30% volume fraction, the energy absorbed up to 50% strain was approximately three times higher than that of the CAD-based sample with an equal volume fraction. Furthermore, the theoretic Gibsonâ»Ashby mode was established in order to predict and design the mechanical properties of the lattice structures. In summary, these results can be used to rapidly create BCC lattice structures with superior compressive properties for engineering applications.