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Zhujing pill (ZP) is a famous Chinese herbal formula that has been widely used to treat diabetic retinopathy, macular degeneration, retinitis pigmentosa and other fundus lesions. In this study, the material basis and mechanism of ZP in the treatment of fundus lesions were evaluated via the high-performance liquid chromatography fingerprint, ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry, network pharmacology and molecular docking. A total of 32 common components were found and 31 components were identified in 15 batches of ZP samples. Moreover, 134 common key targets and 17 putative active components that are connected to fundus lesions were identified. Molecular docking revealed that quercetin, kaempferol, isorhamnetin, 5-O-feruloylquinic acid, plantagoside and 2'-acetylacteoside have the ability to interact with the core targets such as AKT1, TP53, TNF, IL-6 and Jun. Our findings revealed that the therapeutic effects of ZP on fundus lesions are mediated by multiple components, targets and pathways, including at least six active ingredients and 11 targets. The study provides new ideas for further research on the material basis and mechanisms of traditional Chinese medicine prescriptions.
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Medicamentos Herbarios Chinos , Simulación del Acoplamiento Molecular , Farmacología en Red , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/farmacología , Cromatografía Líquida de Alta Presión/métodos , Humanos , Espectrometría de Masas/métodosRESUMEN
Platycodonis Radix (PR), a widely consumed herbal food, and its bioactive constituents, platycodins, have therapeutic potential for lung inflammation. Transient Receptor Potential Ankyrin 1 (TRPA1), which is essential for the control of inflammation, may be involved in the development of inflammation in the lungs. The aim of this study was to determine the TRPA1-targeted effects of PR against pulmonary inflammation and to investigate the affinity of PR constituents for TRPA1 and their potential mechanisms of action. Using a C57BL/6J mouse lipopolysaccharides (LPS) intratracheal instillation pneumonia model and advanced analytical techniques (UPLC-Q-TOF-MS/MS, molecular docking, immuno-fluorescence), five platycodins were isolated from PR, and the interaction between these platycodins and hTRPA1 was verified. Additionally, we analyzed the impact of platycodins on LPS-induced TRPA1 expression and calcium influx in BEAS-2B cells. The results indicated that PR treatment significantly reduced the severity of LPS-triggered inflammation in the mouse model. Interestingly, there was a mild increase in the expression of TRPA1 caused by PR in healthy mice. Among five isolated platycodins identified in the PR extract, Platycodin D3 (PD3) showed the highest affinity for hTRPA1. The interaction between platycodins and TRPA1 was verified through molecular docking methods, highlighting the significance of the S5-S6 pore-forming loop in TRPA1 and the unique structural attributes of platycodins. Furthermore, PD3 significantly reduced LPS-induced TRPA1 expression and calcium ion influx in BEAS-2B cells, substantiating its own role as an effective TRPA1 modulator. In conclusion, PR and platycodins, especially PD3, show promise as potential lung inflammation therapeutics. Further research should explore the precise mechanisms by which platycodins modulate TRPA1 and their broader therapeutic potential.
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Neumonía , Canales de Potencial de Receptor Transitorio , Ratones , Animales , Canales de Potencial de Receptor Transitorio/metabolismo , Lipopolisacáridos/toxicidad , Canal Catiónico TRPA1/metabolismo , Espectrometría de Masas en Tándem , Calcio/metabolismo , Simulación del Acoplamiento Molecular , Ratones Endogámicos C57BL , Neumonía/inducido químicamente , Neumonía/tratamiento farmacológico , Inflamación/inducido químicamente , Inflamación/tratamiento farmacológicoRESUMEN
BACKGROUND: There are limited data to guide the duration and dose of oxygen supplementation for pregnant women undergoing labor. OBJECTIVE: To assess the effect of maternal long-duration high-concentration oxygen administration during labor on umbilical cord venous partial pressure of oxygen. STUDY DESIGN: This randomized clinical trial was conducted between January and October of 2021 in the obstetrics wards of 3 tertiary teaching hospitals in Beijing, China. Women undergoing the latent phase of labor with no existing medical conditions or obstetrical complications who were admitted for delivery were eligible. The women who met inclusion criteria with category I fetal heart rate tracings in labor were randomized in a 1:1 ratio to oxygen or room air. The oxygen group received 10 L of oxygen per minute by simple, tight-fitting face mask until delivery. The room-air group received room air only, without a face mask. The primary outcome was the umbilical cord venous partial pressure of oxygen. RESULTS: A total of 661 women were screened, and 521 were excluded; 140 participants with category I fetal heart rate tracings were enrolled and randomized to oxygen (N=70) or room air (N=70). A total of 135 women with valid paired umbilical cord venous and arterial gas values were included in the umbilical cord venous partial pressure of oxygen and arterial pH analyses. All 140 women were included in the fetal heart rate tracings analysis. Baseline characteristics were similar between the oxygen and room-air groups. The duration of oxygen exposure was approximately 322±147 minutes. There were no differences between the oxygen and room-air groups in the umbilical cord venous partial pressure of oxygen (mean difference, 1.1 mm Hg; 95% confidence interval, -1.0 to 3.2; P=.318) or the proportion of participants with category II fetal heart rate tracings (81.4% vs 78.6%; relative risk, 1.04; 95% confidence interval, 0.88-1.22; P=.672). However, the umbilical cord arterial pH was significantly lower in the oxygen group than in the room-air group (median, 7.23; interquartile range, 7.20-7.27 vs median 7.27; interquartile range, 7.20-7.30; P=.005). CONCLUSION: Maternal long-duration high-concentration oxygen administration during labor did not affect either the umbilical cord venous partial pressure of oxygen or fetal heart rate pattern distribution but resulted in a deterioration of the umbilical cord arterial pH at birth.
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Trabajo de Parto , Oxígeno , Análisis de los Gases de la Sangre , Femenino , Sangre Fetal , Humanos , Recién Nacido , Presión Parcial , Embarazo , Cordón UmbilicalRESUMEN
Hyperglycemia associated with diabetes mellitus (DM) causes oxidative stress, which is involved in the onset and development of diabetic neuropathy. Taurine, a powerful antioxidant, is an effective inhibitor of oxidative stress. The present experiment was conducted to explore the effect of taurine treatment on alterations in body weight, blood glucose, oxidative stress, and Keap1-Nrf2 signaling in the spinal cords of DM rats. The DM rat model was established by STZ injection, and taurine was administered in the drinking water. Body weight and blood glucose were recorded during the experiment. The expression of Gap-43 and MBP proteins was examined by Western blot. Superoxide dismutase (SOD) activity and malondialdehyde (MDA) content were examined as indicators of oxidative stress. The expression of Keap1, Nrf2, and HO-1 gene was examined by real-time PCR. The results showed that compared with the control group, the body weight was decreased, blood glucose was increased, and both Gap-43 and MBP expression were decreased in DM rats, which were all remarkably reversed by taurine treatment. Oxidative stress, as reflected by lower SOD activity and higher MDA concentration, was inhibited in taurine-treated DM rats. Supplemental taurine also downregulated the mRNA level of Keap1, while upregulating Nrf2 and HO-1 mRNA levels. These results showed that taurine inhibits oxidative stress in the spinal cords of DM rats, an effect that might involve the regulation of Keap1-Nrf2 signaling.
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Diabetes Mellitus Experimental , Factor 2 Relacionado con NF-E2 , Animales , Glucemia , Peso Corporal , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/tratamiento farmacológico , Proteína GAP-43/metabolismo , Proteína 1 Asociada A ECH Tipo Kelch/genética , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Estrés Oxidativo , ARN Mensajero/metabolismo , Ratas , Médula Espinal/metabolismo , Superóxido Dismutasa/metabolismo , Taurina/farmacologíaRESUMEN
The goji berry is widely used as tonics; however, the antihuman cervical carcinoma effect and underlying mechanism of goji berry peptide remain to be elucidated. The cyclic peptides are appealing targets in antitumor agent development, and in current study, three novel goji berry cyclic peptides (GCPs) were isolated and amino acid sequence identified. Among them, GCP-1 (Cycle-(Trp-Glu-His-Thr)) inhibited proliferation and induced human cervical cancer (HeLa) cells apoptosis and blocked the HeLa cells in G0/G1 phase significantly. Furthermore, the GCP-1 also inhibited the cervical carcinoma growth in vivo. Moreover, GCP-1 suppressed the cyclin expression and activated the caspase cascade and poly(ADP-ribose) polymerase. Of note, GCP-1 may be a promising novel inhibitor of human cervical cancer.
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Antineoplásicos Fitogénicos/farmacología , Lycium/química , Péptidos Cíclicos/farmacología , Neoplasias del Cuello Uterino/tratamiento farmacológico , Secuencia de Aminoácidos , Animales , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Femenino , Células HeLa , Humanos , Ratones , Ratones Endogámicos BALB C , Neoplasias Experimentales/tratamiento farmacológico , Neoplasias Experimentales/patología , Péptidos Cíclicos/química , Péptidos Cíclicos/aislamiento & purificación , Neoplasias del Cuello Uterino/patologíaRESUMEN
MicroRNA-98-5p (miR-98-5p) is a stress-related microRNA (miRNA) that plays an important role in regulating cell survival, apoptosis, and oxidative stress in multiple cell types and diseases. However, little is known about the role of miR-98-5p in cerebral ischemia/reperfusion injury. In this study, we investigated the role and mechanism of miR-98-5p in regulating neuronal injury induced by oxygen-glucose deprivation/reoxygenation (OGD/R), an in vitro model of cerebral ischemia/reperfusion injury. We found that miR-98 expression was significantly altered in neurons in response to OGD/R treatment. Functional experiments showed that overexpression of miR-98-5p inhibited OGD/R-induced apoptosis and reactive oxygen species (ROS) production in neurons, whereas inhibition of miR-98-5p showed the opposite effect. Interestingly, bioinformatics analysis predicted that BTB and CNC homology 1 (Bach1) was a potential target gene of miR-98-5p, that was verified by dual-luciferase reporter assay. Moreover, overexpression of miR-98-5p inhibited Bach1 expression while suppression of miR-98-5p promoted Bach1 expression in neurons. Notably, miR-98-5p was shown to regulate the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and the activity of the antioxidant response element (ARE). However, overexpression of Bach1 or silencing of Nrf2 significantly abolished the miR-98-5p-mediated neuroprotective effect. Overall, these results demonstrate that miR-98-5p ameliorates OGD/R-induced neuronal injury in vitro through targeting to promote activation of Nrf2/ARE signaling. Our study suggests that miR-98-5p may play a potential role in cerebral ischemia/reperfusion injury and represents a potential therapeutic target for neuroprotection.
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Elementos de Respuesta Antioxidante/genética , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/metabolismo , Glucosa/deficiencia , MicroARNs/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Neuronas/metabolismo , Neuronas/patología , Oxígeno/efectos adversos , Animales , Línea Celular , Regulación de la Expresión Génica , Silenciador del Gen , Ratones , MicroARNs/genética , Modelos Biológicos , Neuroprotección , Especies Reactivas de Oxígeno/metabolismo , Transducción de SeñalRESUMEN
In this Letter, a new type of single-mode slotted laser used for an on-chip light source in photonic integrated circuits is proposed. An inclined light beam with a low vertical divergence angle can be directly coupled into the surface grating of the silicon to form an integrated light source. Experimentally, a III-V laser with a 54.6° inclined angle and a vertical divergence angle of 1.7° is achieved by introducing a kind of specially distributed microstructure. The side mode suppression ratio is better than 45 dB, and the continuous wave output power reaches 6.5 mW at room temperature. We report the inclined emitting microstructured single-mode laser with a low divergence angle for the first time, to the best of our knowledge.
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Hazelnut, one of the most popular tree nuts, is widely found in processed food and even very small amounts can trigger severe allergic reactions in susceptible people. Herein, we developed a sensitive and rapid method based on CRISPR and qPCR capable of detecting low-abundance hazelnut in processed food. The assay, known as CRISPR-based nucleic acid test method (Crinac) can detect 1 % of hazelnut in a mixture and allows the species to be identified in a complex processed sample. The detection process can be completed within 60 min. Contributed to amplification via PCR and CRISPR/Cas12a, enables end-fluorescence measurement for the quantification of hazelnut, thus reducing assay time and eliminating the need for costly real-time fluorescence PCR instruments. The assay based on CRISPR/Cas12 and PCR has potential as a sensitive and reliable analytical tool for the detection of food authenticity.
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Corylus , Proteínas de Plantas , Humanos , Proteínas de Plantas/análisis , Corylus/genética , Sistemas CRISPR-Cas , Análisis de los Alimentos/métodos , Técnicas de Amplificación de Ácido Nucleico/métodos , Reacción en Cadena en Tiempo Real de la Polimerasa/métodosRESUMEN
The SARS-CoV-2, responsible for the COVID-19 pandemic, poses a significant threat to global healthcare. Peptide and peptide-based inhibitors, known for their safety, efficacy, and selectivity, have recently emerged as promising candidates for treating late-developing viral infections. In this study, three peptides were selected to target different stages of viral invasion, specifically ACE2 and S protein binding, as well as membrane fusion. The objective was to assess their ability to impede the entry of the SARS-CoV-2 Spike pseudotyped virus. Our findings revealed that a combination of these three peptides demonstrated enhanced antiviral effects. This outcome substantiates the feasibility of developing effective peptide combinations to combat diseases related to SARS-CoV-2. Moreover, the three-peptide combinations, designed to target multiple aspects of SARS-CoV-2 viral entry, exhibited heightened viral inhibition and broad-spectrum antiviral properties.
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The COVID-19 pandemic was the most significant public healthcare crisis worldwide. It was estimated that 80% of infected patients with COVID-19 have not fully recovered and developed one or more long-term symptoms, referred to as post-acute sequelae of COVID-19 (PASC). Seeking a treatment strategy for PASC has become a concerning topic since the sequelae can cause irreversible multiple organ damage and can severely compromise quality of life. It is indicated that PASC may be closely related to lung injury-induced hypoxia, excessive immune response, cytokine storm, gut bacteria imbalance, and endothelial dysfunction. Also, more and more research has indicated that angiotensin-converting enzyme 2 (ACE2) receptor, transient receptor potential ankyrin 1 and vanillin 1 (TRPA1/V1), and nuclear factor erythroid 2-related factor 2 (Nrf2) can be considered as the targets to treat PASC. There is currently still no proven medication for PASC due to its complexity. Many clinical practices and studies have shown that natural products have great potential in preventing and treating PASC. Therefore, we intended to provide a comprehensive review of the current literature on PASC and the role of natural ingredients in PASC management. Meanwhile, this review provided meaningful insight for further study of natural ingredients to improve PASC and its clinical application.
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Productos Biológicos , COVID-19 , Humanos , Productos Biológicos/farmacología , Productos Biológicos/uso terapéutico , Pandemias , Calidad de Vida , Síndrome Post Agudo de COVID-19 , Progresión de la EnfermedadRESUMEN
Numerous studies indicated that long non-coding RNAs (lncRNAs) play critical roles in glioma initiation and progression. SNHG25 is a newly identified lncRNA. And the functional role and molecular mechanism of SNHG25 in glioma cells have not been investigated. In this study, we found that SNHG25 was upregulated in glioma cells and tissues. CCK-8, EDU, and colony formation assays demonstrated that SNHG25 knockdown markedly inhibited glioma cell proliferation. In vivo studies showed that SNHG25 knockdown significantly inhibited tumor growth. Further studies indicated that SNHG25 positively regulated MAP2K2 through sponging miR-579-5p. High expression of SNHG25 activated MAPK signaling through MAP2K2. These data suggest that SNHG25 is a potential target and biomarker for glioma.
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Glioma , MicroARNs , ARN Largo no Codificante , Línea Celular Tumoral , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , Glioma/patología , Humanos , MicroARNs/genética , MicroARNs/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Sincalida/genética , Sincalida/metabolismoRESUMEN
Platycodonis Radix (Jiegeng), the dried root of Platycodon grandiflorum, is a traditional herb used as both medicine and food. Its clinical application for the treatment of cough, phlegm, sore throat, pulmonary and respiratory diseases has been thousands of years in China. Platycodin D is the main active ingredient in Platycodonis Radix, which belongs to the family of pentacyclic triterpenoid saponins because it contains an oleanolane type aglycone linked with double sugar chains. Modern pharmacology has demonstrated that Platycodin D displays various biological activities, such as analgesics, expectoration and cough suppression, promoting weight loss, anti-tumor and immune regulation, suggesting that Platycodin D has the potential to be a drug candidate and an interesting target as a natural product for clinical research. In this review, the distribution and biotransformation, pharmacological effects, metabolic mechanism and safety evaluation of Platycodin D are summarized to lay the foundation for further studies.
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Saponinas , Triterpenos , Biotransformación , Tos , Humanos , Saponinas/efectos adversos , Saponinas/metabolismo , Triterpenos/efectos adversosRESUMEN
Increasing evidence suggests that n-hexane induces nerve injury via neuronal apoptosis induced by its active metabolite 2,5-hexanedione (HD). However, the underlying mechanism remains unknown. Studies have confirmed that pro-nerve growth factor (proNGF), a precursor of mature nerve growth factor (mNGF), might activate apoptotic signaling by binding to p75 neurotrophin receptor (p75NTR) in neurons. Therefore, we studied the mechanism of the proNGF/p75NTR pathway in HD-induced neuronal apoptosis. Sprague-Dawley (SD) rats were injected with 400 mg/kg HD once a day for 5 weeks, and VSC4.1 cells were treated with 10, 20, and 40 mM HD in vitro. Results showed that HD effectively induced neuronal apoptosis. Moreover, it up-regulated proNGF and p75NTR levels, activated c-Jun N-terminal kinase (JNK) and c-Jun, and disrupted the balance between B-cell lymphoma-2 (Bcl-2) and Bcl-2-associated X protein (Bax). Our findings revealed that the proNGF/p75NTR signaling pathway was involved in HD-induced neuronal apoptosis; it can serve as a theoretical basis for further exploration of the neurotoxic mechanisms of HD.
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Apoptosis , Hexanonas/farmacología , Factores de Crecimiento Nervioso/metabolismo , Neuronas/metabolismo , Neurotoxinas/farmacología , Precursores de Proteínas/metabolismo , Médula Espinal/efectos de los fármacos , Animales , Línea Celular Tumoral , Hexanonas/toxicidad , MAP Quinasa Quinasa 4/metabolismo , Masculino , Proteínas del Tejido Nervioso/metabolismo , Neuronas/efectos de los fármacos , Neurotoxinas/toxicidad , Ratas , Ratas Sprague-Dawley , Receptores de Factores de Crecimiento/metabolismo , Transducción de Señal , Médula Espinal/citología , Médula Espinal/metabolismoRESUMEN
Furanodiene is a sesquiterpene extracted from the essential oil of the rhizome of Curcuma wenyujin Y.H. Chen et C. Ling (Wen Ezhu). Furanodiene is the primary component in Wen Ezhu's essential oil, accounting for more than 20% by weight. In vitro, MTT assay was used to compare the inhibitory effects of furanodiene and Wen Ezhu's essential oil on 11 human cancer cell lines. Compared to the essential oil, furanodiene showed stronger growth inhibitions on Hela, Hep-2, HL-60, PC3, SGC-7901 and HT-1080 cells with IC(50) between 0.6-4.8 microg/ml. In vivo, furanodiene was also found to exhibit inhibitory effects on the growth of uterine cervical (U14) and sarcoma 180 (Sl80) tumors in mice. Our data suggests that furanodiene, an active component from the essential oil of Wen Ezhu, possesses efficacy against uterine cervical cancer.
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Curcuma , Medicamentos Herbarios Chinos/farmacología , Furanos/farmacología , Compuestos Heterocíclicos con 2 Anillos/farmacología , Sesquiterpenos/farmacología , Neoplasias del Cuello Uterino/tratamiento farmacológico , Adenocarcinoma , Animales , Neoplasias de la Mama , Carcinoma Hepatocelular , División Celular/efectos de los fármacos , Femenino , Fibrosarcoma/tratamiento farmacológico , Fibrosarcoma/patología , Células HL-60 , Células HeLa , Humanos , Células K562 , Leucemia , Neoplasias Hepáticas , Neoplasias Pulmonares , Ratones , Ratones Endogámicos , Tamaño de los Órganos , Bazo/patología , Timo/patología , Neoplasias del Cuello Uterino/patología , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Lymphatic metastasis is a major mechanism of tumor metastasis. The present study aimed to investigate the association of CRKII, a member of the CRK family, with the in vitro malignant behaviors of a murine hepatocarcinoma Hca-P cell line, with a lymph node metastatic rate of ~25%. Total mRNA was extracted from Hca-P cells, and then the murine CRKII gene was amplified by polymerase chain reaction and cloned into the pEASY-blunt cloning vector. Subsequently, the recombinant pcDNA3.1/V5-HisB-CRKII plasmid was constructed and transfected into Hca-P cells. Western blotting indicated that the CRKII expression level in pcDNA3.1/V5-HisB-CRKII-Hca-P cells was increased by ~185%, compared with pcDNA3.1/V5-HisB-Hca-P cells. The stable overexpression of CRKII enhanced the in vitro proliferation ability, as measured with a Cell Counting Kit-8 assay, and the colony forming capacity was measured with a soft agar colony forming assay for Hca-P cells. The in vitro migration and invasion capacities of Hca-P cells were increased by ~179 and 156% in Hca-P cells, respectively, following the stable upregulation of CRKII. Collectively, the recombinant pcDNA3.1/V5-HisB-CRKII-Hca-P plasmid was constructed successfully. Additionally, the CRKII expression level was positively associated with the in vitro proliferation, migration and invasion malignant properties of Hca-P cells.
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OBJECTIVE: This study aims to explore the clinical efficacy of CpG-based therapy for treating hepatocellular carcinoma (HCC) by skewing polarization toward M1 macrophage from M2. METHODS: Pulmonary metastasis rate, overall survival time, and remission rate of 10 patients with HCC treated with transcatheter arterial chemoembolization (TACE) combined with CpG therapy and 10 age-, gender-, and TNM0-matched patients treated with TACE (control group) were compared. RESULTS: No pulmonary metastasis rate was 70% in the combined treatment group and 40% in the control group, respectively; and the differences between the two groups were statistically significant (p < 0.05). Median overall survival time was 22 months in the combined treatment group, compared with 6.65 months in the control group (p < 0.05). Remission rate in the combined treatment group (70%) was higher than in the control group (30%), but the differences between these two groups were not statistically significant (p > 0.05). CONCLUSION: Compared with TACE, CpG combined with TACE can decrease the pulmonary metastasis rate. This combined therapy can also improve the overall survival time of patients.
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Carcinoma Hepatocelular/inmunología , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/terapia , Macrófagos/inmunología , Oligodesoxirribonucleótidos/uso terapéutico , Anciano , Anciano de 80 o más Años , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Estudios de Casos y Controles , Polaridad Celular/fisiología , Quimioembolización Terapéutica , Femenino , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/prevención & control , Neoplasias Pulmonares/secundario , Macrófagos/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Análisis de SupervivenciaRESUMEN
The Raman enhancing ability of noble metal nanoparticles (NPs) is an important factor for surface enhanced Raman scattering (SERS) substrate screening, which is generally evaluated by simply mixing as-prepared NPs with Raman reporters for Raman signal measurements. This method usually leads to incredible results because of the NP surface coverage nonuniformity and reporter-induced NP aggregation. Moreover, it cannot realize in situ, continuous SERS characterization. Herein, we proposed a dynamic SERS monitoring strategy for NPs with precisely tuned structures based on a simplified spatially confined NP growth method. Gold nanorod (AuNR) seed NPs were coated with a mesoporous silica (mSiO2) shell. The permeability of mSiO2 for both reactive species and Raman reporters rendered the silver overcoating reaction and SERS indication of NP growth. Additionally, the mSiO2 coating ensured monodisperse NP growth in a Raman reporter-rich reaction system. Moreover, "elastic" features of mSiO2 were observed for the first time, which is crucial for holding the growing NP without breakage. This feature makes the mSiO2 coating adhere to metal NPs throughout the growing process, providing a stable Raman reporter distribution microenvironment near the NPs and ensuring that the substrate's SERS ability comparison is accurate. Three types of NPs, i.e., core-shell Au@AgNR@mSiO2, Au@AuNR@mSiO2, and yolk-shell Au@void@AuNR@mSiO2 NPs, were synthesized via core-shell overgrowth and galvanic replacement methods, showing the versatility of the approach. The living cell SERS labeling ability of Au@AgNR@mSiO2-based tags was also demonstrated. This strategy addresses the problems of multiple batch NP preparation, aggregation, and surface adsorption differentiation, which is a breakthrough for the dynamic comparison of SERS ability of metal NPs with precisely tuned structures and optical properties.
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Cristalización/métodos , Ensayo de Materiales/métodos , Nanopartículas del Metal/química , Dióxido de Silicio/química , Espectrometría Raman/métodos , Módulo de Elasticidad , Oro/química , Luz , Nanopartículas del Metal/ultraestructura , Porosidad , Dispersión de Radiación , Plata/químicaRESUMEN
OBJECTIVE: To determine whether the necrotic tumor cell-stimulated macrophages (NTCSM) could elicit specific immune response. METHODS: Mice were immunized with the necrotic H22 tumor cell lysate-stimulated macrophages and the specific immune responses against the same tumor challenge were examined. The morphologic characteristics were observed with the transmission electron microscope and scanning electron microscopy. The expression of CD14, CD68, CD80 and CD86 were detected with the flow cytometer. The cytotoxicity and cytokine production of splenocytes were measured with the MTT assay and ELISA assay respectively. RESULTS: Our research results reveal that NTCSMs are larger cells which generally generate spherical and elongated protrusions, folding membrane, and vesicles on their surface. Also, abundant lysosomes, secondary lysosomes, phagosomes, rough endoplasmic reticulum, and lipid bodies were found in their cytoplasm. The flow cytometry results show that the necrotic H22 tumor cell lysate could enhance the expression of CD14 and CD86 molecules and the NTCSM was characterized by the expression of CD14+/-CD68+CD80-CD86+. After the mice were vaccinated with NTCSMs, the tumor forming rate, tumor volume and weight of the NTCSM-vaccinated group were significantly lower than those of the sterile saline-injected group and untreated macrophage-vaccinated group (p<0.05). The cytotoxicity to H22 tumor cells of the splenocytes obtained from the NTCSM-immunized group was higher than that of the sterile saline-injected group and untreated macrophage-vaccinated group (p<0.05). Meanwhile, the levels of IL-2 and IFN-γ in the culture supernatant of the NTCSM-immunized group were higher significantly than those of the saline-injected group and untreated macrophage-vaccinated group. The level of IL-4 of the NTCSM-immunized group was significantly lower than those of the other two groups. CONCLUSION: Our results indicated that NTCSMs could elicit specific cellular immune responses in vivo.
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Vacunas contra el Cáncer/inmunología , Carcinoma Hepatocelular/inmunología , Neoplasias Hepáticas/inmunología , Hígado/patología , Macrófagos Peritoneales/inmunología , Animales , Antígenos de Neoplasias/inmunología , Diferenciación Celular , Extractos Celulares/inmunología , Línea Celular Tumoral , Citocinas/metabolismo , Humanos , Inmunidad Celular , Macrófagos Peritoneales/trasplante , Ratones , Ratones Endogámicos BALB C , Necrosis , Trasplante de Neoplasias , Carga TumoralRESUMEN
Recently surface-enhanced Raman scattering (SERS) imaging guided theranostic nanoplatforms have attracted considerable attention. Herein, we developed novel yolk-shell gold nanorod@void@mesoporous titania nanoparticles (AuNR@void@mTiO2 NPs) for simultaneous SERS imaging and chemo-photothermal therapy. Our work showed three highlighted features: first, we proposed a facile and versatile "up to down" SERS labeling strategy for the drug delivery system, in which "empty carriers" were pre-synthesized, followed by co-loading of Raman reporters on AuNR and anti-cancer drug doxorubicin (DOX) in mTiO2 in sequence. The acquired SERS signal was strong enough for tracking NPs at both living cells and mice levels. Second, we selected mTiO2 as a novel drug loading material instead of the widely used mesoporous silica (mSiO2). The mTiO2 shared satisfactory drug loading and release behavior as mSiO2 but it was chemically inert. This property not only provided a facile way to form a yolk-shell structure but also rendered it with superior structural stability in a biological system. Third, the near infrared (NIR) light absorbing property of the AuNR SERS substrate was also explored for drug release regulation and photothermal treatment. Significantly greater MCF-7 cell killing was observed when treated together with DOX-loaded NPs and NIR laser irradiation, attributable to the synergistic chemo-thermal therapeutic effect. Our results indicated the established SERS labeled yolk-shell NP as a promising theranostic platform and suggested its potential in vivo applications.