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BACKGROUND: Metastasis driven by epithelial-mesenchymal transition (EMT) remains a significant contributor to the poor prognosis of colorectal cancer (CRC), and requires more effective interventions. GPR81 signaling has been linked to tumor metastasis, while lacks an efficient specific inhibitor. PURPOSE: Our study aimed to investigate the effect and mechanism of Gentisic acid on colorectal cancer (CRC) metastasis. STUDY DESIGN: A lung metastasis mouse model induced by tail vein injection and a subcutaneous graft tumor model were used. Gentisic acid (GA) was administered by an intraperitoneal injection. HCT116 was treated with lactate to establish an in vitro model. METHODS: MC38 cells with mCherry fluorescent protein were injected into tail vein to investigate lung metastasis ability in vivo. GA was administered by intraperitoneal injection for 3 weeks. The therapeutic effect was evaluated by survival rates, histochemical analysis, RT-qPCR and live imaging. The mechanism was explored using small interfering RNA (siRNA), Western blotting, RT-qPCR and immunofluorescence. RESULTS: GA had a therapeutic effect on CRC metastasis and improved survival rates and pathological changes in dose-dependent manner. GA emerged as an GPR81 inhibitor, effectively suppressed EMT and mTOR signaling in CRC induced by lactate both in vivo and in vitro. Mechanistically, GA halted lactate-induce degradation of DEPDC5 through impeding the activation of Chaperone-mediated autophagy (CMA). CONCLUSION: CMA-mediated DEPDC5 degradation is crucial for lactate/GPR81-induced CRC metastasis, and GA may be a promising candidate for metastasis by inhibiting GPR81 signaling.
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Neoplasias Colorrectales , Transición Epitelial-Mesenquimal , Neoplasias Pulmonares , Receptores Acoplados a Proteínas G , Animales , Receptores Acoplados a Proteínas G/metabolismo , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/tratamiento farmacológico , Humanos , Ratones , Transición Epitelial-Mesenquimal/efectos de los fármacos , Neoplasias Pulmonares/secundario , Neoplasias Pulmonares/tratamiento farmacológico , Células HCT116 , Transducción de Señal/efectos de los fármacos , Línea Celular Tumoral , Masculino , Serina-Treonina Quinasas TOR/metabolismoRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Physalis angulata L., a traditional Chinese medicine called "Kuzhi" in China, was used traditionally to treat liver diseases (eg. icterus, hepatitis) as well as malaria, asthma, and rheumatism. AIM OF THE STUDY: Our study aimed to investigate the withanolides with anti-hepatic fibrosis effect from P. angulate. MATERIALS AND METHODS: Withanolides were obtained from the EtOH extract of P. angulate by bioassay-molecular networking analysis-guided isolation using column chromatography and normal/reversed-phase semipreparative HPLC. The structures of new withanolides were elucidated by combinations of spectroscopic techniques with NMR and ECD calculations. MTT cell viability assay, AO/EB staining method, cell wound healing assay, ELISA and Western blot experiments were employed to evaluate the anti-hepatic fibrosis activity and to uncover related mechanism. Molecular docking analysis and cellular thermal shift assay were used to evaluate and verify the interaction between the active withanolides and their potential targets. RESULTS: Eight unreported withanolides, withagulides A-H (1-8), along with twenty-eight known ones were obtained from P. angulate. Withanolides 6, 9, 10, 24, 27, and 29-32 showed marked anti-hepatic fibrosis effect with COL1A1 expression inhibition above 50 %. Physalin F (9), the main component in the active fraction, significantly decreased the TGF ß1-stimulated expressions of collagen I and α-SMA in LX-2 cells. Mechanism study revealed that physalin F exerted its anti-hepatic fibrosis effect via the PI3K/AKT/mTOR signaling pathway. CONCLUSION: This study suggested that withanolides were an important class of natural products with marked anti-hepatic fibrosis effect. The main withanolide physalin F might be a promising candidate for hepatic fibrosis treatment. The work provided experimental foundation for the use of P. angulate to treat hepatic fibrosis.
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Physalis , Witanólidos , Witanólidos/farmacología , Witanólidos/uso terapéutico , Witanólidos/química , Physalis/química , Simulación del Acoplamiento Molecular , Fosfatidilinositol 3-Quinasas , Cirrosis Hepática/inducido químicamente , Cirrosis Hepática/tratamiento farmacológico , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Extractos Vegetales/químicaRESUMEN
Radix Astragali is one of the most famous and frequently used health food supplements and herbal medicines. Among more than 227 components of Radix Astragali, Astragaloside IV (AG IV) is famous functional compound and is commonly used as a quality marker for Radix Astragali. However, the relatively low content of AG IV in Radix Astragali (< 0.04%, w/w) severely limits its application. The purpose of this study is to improve the biotransformation of AG IV and its bioaccessibility during in vitro digestion by Poria cocos solid fermenting Radix Astragali. The optimum fermentation conditions were as follows: Inoculation amount 8 mL; fermentation time 10 d; fermentation humidity 90%. Through fermentation, the content of AG IV was increased from 384.73 to 1986.49 µg/g by 5.16-fold. After in vitro digestion, the contents of genistin, calycosin, formononetin, AG IV, Astragaloside II (AG II) and total flavonoids in fermented Radix Astragali (FRA) of enteric phase II (ENTII) were 34.52 µg/g, 207.32 µg/g, 56.76 µg/g, 2331.46 µg/g, 788.31 µg/g, 3.37 mg/g, which were 2.08-fold, 2.51-fold, 1.05-fold, 8.62-fold, 3.22-fold and 1.50-fold higher than those of control, respectively. The Scanning electron microscopy (SEM) of FRA showed rough surface and porous structure. The DPPH and ABTS radical scavenging rate of FRA were higher than those of control. These results showed that the Poria cocos solid fermentation could increase the content of the AG IV in Radix Astragali and improve the bioaccessibility and antioxidant activity of Radix Astragali, which is providing new ideas for future development and utilization of Radix Astragali.
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Medicamentos Herbarios Chinos , Wolfiporia , Antioxidantes , Fermentación , Medicamentos Herbarios Chinos/química , Biotransformación , Digestión , Cromatografía Líquida de Alta Presión/métodosRESUMEN
α-Lipoic acid (α-LA) was usually applied to improve the ability of removing the reactive oxygen species of host. The affection of α-LA on ruminants was mainly focused on the variation of serum antioxidant and immune indexes, but the research on tissues or organs remained limited. The aim of this study was to explore the effects of dietary supplementation with different levels of α-LA on growth performance, antioxidant status, and immune indexes of serum and tissues in sheep. One hundred Duhu F1 hybrid (Dupoâ × Hu sheepâ) sheep aged 2 to 3 mo with similar body weight (27.49 ± 2.10 kg) were randomly allocated into five groups. Five diets supplemented with 0 (CTL), 300 (LA300), 450 (LA450), 600 (LA600), and 750 (LA750) mg/kg α-LA were fed to sheep for 60 d. The results showed that α-LA supplementation significantly increased the average daily feed intake (P < 0.05); however, no significant variation was found in the average daily gain, feed conversion rate, carcass weight, and slaughter rate among groups (P > 0.05). Compared with CTL group, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities in serum of LA600 and LA750 groups were increased (P < 0.05). At LA450-LA750 groups, SOD, CAT activities in liver and ileum tissues and GSH-Px activities in ileum tissues were increased than CTL group (P < 0.05), while malondialdehyde (MDA) contents in serum and muscle tissue were decreased than CTL group (P < 0.05). The total antioxidant capacity contents in liver, muscle, and ileum tissues of LA600 group were increased compared with CTL group (P < 0.05). Additionally, the interleukin-10 (IL-10) contents of serum in LA450-LA750 groups were increased than CTL group (P < 0.05); the contents of interleukin-1ß (IL-1ß) in serum, interleukin-2 (IL-2) in liver, and interleukin-6, IL-1ß in muscle were decreased than CTL group (P < 0.05). The content of immunoglobulin A in serum of LA600 group, ileum, and muscle of LA750 group was increased than CTL group (P < 0.05). Based on the quadratic regression analysis of GSH-Px, MDA, IL-2, IL-10, and IL-1ß, the optimal dietary α-LA levels were estimated to be 495.75, 571.43, 679.03, 749.75, and 678.25 mg/kg, respectively. This research will provide certain contribution for the effective utilization of α-LA in sheep production.
This article studied the effects of α-lipoic acid (α-LA) on growth performance, antioxidant capacity, and immune function of serum and tissues in sheep. α-LA was usually applied to improve the ability of removing the reactive oxygen species of host. The affection of α-LA on ruminants was mainly focused on the variation of serum antioxidant and immune indexes, but the research on tissues or organs remained limited. One hundred sheep aged 2 to 3 mo were randomly allocated into five groups; five diets supplemented with 0, 300, 450, 600, and 750 mg/kg α-LA were fed to sheep for 60 d. Results showed that adding appropriate α-LA in diet has the potential ability to improve the production performance, increase the activity of antioxidant enzymes, and regulate the secretion of inflammatory factors in sheep serum, rumen epithelium, liver, ileum, and muscle tissues. Therefore, these results indicated that α-LA has the potential to become a safe, high-quality, and environmentally friendly feed additive that could protect the health of sheep and improve the economic benefits of pasture.
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Antioxidantes , Ácido Tióctico , Animales , Ovinos , Ácido Tióctico/farmacología , Interleucina-2 , Interleucina-10 , Suplementos Dietéticos/análisis , Dieta/veterinaria , Superóxido Dismutasa , Inmunidad , Alimentación Animal/análisisRESUMEN
Background: In the clinical treatment of large bone defects, distraction osteogenesis can be used. However, some patients may suffer from poor bone regeneration, or even delayed healing or non-union. Problems with the aggregation and proliferation of primary osteoblasts, or problems with the differentiation of primary osteoblasts will lead to poor bone regeneration. Therefore, supplementing exogenous primary osteoblasts and growth factors when using distraction osteogenesis may be a treatment plan with great potential. Methods: Bone marrow mesenchymal stem cells (BMSCs) were extracted from rats and cultured. Subsequently, Recombinant Rat Platelet-derived Growth Factor BB (rrPDGF-BB) was used to induce bone marrow mesenchymal stem cells. At the same time, male adult rats were selected to make the right femoral distraction osteogenesis model. During the mineralization period, phosphate buffer salt solution (control group), non-induction bone marrow mesenchymal stem cells (group 1) and recombinant rat platelet-derived growth factor BB intervened bone marrow mesenchymal stem cells (group 2) were injected into the distraction areas of each group. Then, the experimental results were evaluated with imaging and histology. Statistical analysis of the data showed that the difference was statistically significant if p < 0.05. Results: After intervention with recombinant rat platelet-derived growth factor BB on bone marrow mesenchymal stem cells, the cell morphology changed into a thin strip. After the cells were injected in the mineralization period, the samples showed that the callus in group 2 had greater hardness and the color close to the normal bone tissue; X-ray examination showed that there were more new callus in the distraction space of group 2; Micro-CT examination showed that there were more new bone tissues in group 2; Micro-CT data at week eight showed that the tissue volume, bone volume, percent bone volume, bone trabecular thickness, bone trabecular number and bone mineral density in group 2 were the largest, and the bone trabecular separation in group 2 was the smallest. There was a statistical difference between the groups (p < 0.05); HE staining confirmed that group 2 formed more blood vessels and chondrocytes earlier than the control group. At 8 weeks, the bone marrow cavity of group 2 was obvious, and some of them had been fused. Conclusion: The study confirmed that injecting bone marrow mesenchymal stem cellsBB into the distraction space of rats can promote the formation of new bone in the distraction area and promote the healing of distraction osteogenesis.
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The integration of various two-dimensional (2D) materials on wafers enables a more-than-Moore approach for enriching the functionalities of devices1-3. On the other hand, the additive growth of 2D materials to form heterostructures allows construction of materials with unconventional properties. Both may be achieved by materials transfer, but often suffer from mechanical damage or chemical contamination during the transfer. The direct growth of high-quality 2D materials generally requires high temperatures, hampering the additive growth or monolithic incorporation of different 2D materials. Here we report a general approach of growing crystalline 2D layers and their heterostructures at a temperature below 400 °C. Metal iodide (MI, where M = In, Cd, Cu, Co, Fe, Pb, Sn and Bi) layers are epitaxially grown on mica, MoS2 or WS2 at a low temperature, and the subsequent low-barrier-energy substitution of iodine with chalcogens enables the conversion to at least 17 different 2D crystalline metal chalcogenides. As an example, the 2D In2S3 grown on MoS2 at 280 °C exhibits high photoresponsivity comparable with that of the materials grown by conventional high-temperature vapour deposition (~700-1,000 °C). Multiple 2D materials have also been sequentially grown on the same wafer, showing a promising solution for the monolithic integration of different high-quality 2D materials.
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Tea consumption may potentially promote the prevalence of neural tube defects (NTDs) because catechins, the main components of tea polyphenols, can lead to the depletion of bioavailable folate. Many epidemiologic studies have explored the association between tea consumption and NTD risk; however, the findings are inconsistent. This systematic review and meta-analysis investigated the association between tea consumption and NTD. We hypothesized that tea consumption during the periconceptional period would significantly promote NTD prevalence. Three electronic databases (PubMed, Web of Science, and Embase) were searched from their inception through July 14, 2021. Pooled odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were obtained using random-effects models. Subgroup analyses were performed to explore potential confounders. In addition, a dose-response analysis was conducted to examine further the association between tea consumption and NTD. Seven articles with nine studies yielded 2834 cases and 19,924 participants. The results showed that tea consumption during the periconceptional period did not significantly increase NTD prevalence (OR, 1.37; 95% CI, 0.96-1.95; P = .08). This finding was consistent with the evaluation of 3 subtypes of NTDs: anencephaly (OR, 1.36; 95% CI, 0.84-2.20; P = .22), spina bifida (OR, 1.51; 95% CI, 0.84-2.72; P = .17), and encephalocele (OR, 0.99; 95% CI, 0.46-2.15; P = .98). Furthermore, a significant dose-response association between tea consumption and the risk of NTDs was not evident (P > .05). Our meta-analysis suggests that maternal tea consumption during the periconceptional period did not significantly increase the prevalence of NTDs. Further studies are needed to ascertain the association between tea consumption and NTD prevalence.
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Defectos del Tubo Neural , Estudios de Casos y Controles , Humanos , Defectos del Tubo Neural/epidemiología , Defectos del Tubo Neural/etiología , Defectos del Tubo Neural/prevención & control , Prevalencia , Factores de Riesgo , TéRESUMEN
The multifunctional combined nanoplatform has a wide application prospect in the synergistic treatment of cancer. Nevertheless, the traditional treatment of phototherapy is limited by the catalytic nanomaterial itself, so the effect is not satisfactory. Here, the arris of the anisotropic truncated octahedral Au (TOh Au) was coated with noble metal Pt to form a spatial separation structure, which enhanced the local surface plasmonic resonance and thus boosted the photocatalytic effect. In this system, the highly efficient photocatalysis provides a strong guarantee for oncotherapy. On the one hand, the structure of arris deposition adequately improves the efficiency of photothermal conversion, which substantially improves the effectiveness of photothermal therapy. On the other hand, in situ oxygen production of Pt ameliorates tumor hypoxia, and through the O2 self-production and sales mode, the growth and development of tumor were inhibited. Meanwhile, under the enhanced photocatalysis, more O2 were produced, which greatly evolved the treatment effect of photodynamic therapy. In the end, the addition of hyaluronic acid can specifically target osteosarcoma cells while improving the retention time and biocompatibility of the material in the body. Thus, the nanocomposite shows superexcellent synergistic enhancement of photothermal conversion efficiency and photodynamic capability in vitro and in vivo, which provides a potential possibility for osteosarcoma cure.
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Antineoplásicos/uso terapéutico , Nanopartículas del Metal/uso terapéutico , Osteosarcoma/tratamiento farmacológico , Fármacos Fotosensibilizantes/uso terapéutico , Animales , Anisotropía , Antineoplásicos/química , Antineoplásicos/efectos de la radiación , Antineoplásicos/toxicidad , Catálisis/efectos de la radiación , Clorofilidas , Oro/química , Oro/toxicidad , Ácido Hialurónico/química , Ácido Hialurónico/toxicidad , Rayos Infrarrojos , Nanopartículas del Metal/química , Nanopartículas del Metal/efectos de la radiación , Nanopartículas del Metal/toxicidad , Ratones Desnudos , Osteosarcoma/metabolismo , Oxígeno/metabolismo , Fotoquimioterapia , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/efectos de la radiación , Fármacos Fotosensibilizantes/toxicidad , Terapia Fototérmica , Platino (Metal)/química , Platino (Metal)/toxicidad , Polietilenglicoles/química , Polietilenglicoles/toxicidad , Porfirinas/química , Porfirinas/efectos de la radiación , Porfirinas/uso terapéutico , Especies Reactivas de Oxígeno/metabolismo , Resonancia por Plasmón de SuperficieRESUMEN
BACKGROUND: To evaluate the efficacy and safety of transjugular intrahepatic portosystemic shunt (TIPS) on hepatic sinusoidal obstruction syndrome (HSOS) associated with consumption of Gynura segetum (GS). METHODS: We retrospectively reviewed 9 consecutive patients with GS-related HSOS who were refractory to supportive treatment and underwent TIPS at our institution between January 2014 and September 2019. The patients were evaluated for safety and efficacy, including TIPS complications and changes in portosystemic pressure gradient (PPG), ascites, total bilirubin, liver size and portal vein diameter. RESULTS: TIPS procedures were performed successfully in the 9 patients, and no technically-related complications due to the TIPS procedure were recorded. The PPG was improved by TIPS in all patients (mean PPG before TIPS, 30.4 ± 5.2 vs. 13.0 ± 4.1 mm Hg post-TIPS, P = 0.008). One patient who was lost to follow-up, whereas the remaining 8 patients survived with a median follow-up period of 12 months (range 5-39 months). Although the total bilirubin was significantly increased 5-7 days after TIPS compared with that before the procedure (3.57 ± 1.58 vs. 4.82 ± 2.06 mg/dl, P = 0.017), it returned to baseline levels at 1-month follow-up (3.53 ± 2.72 vs. 4.82 ± 2.06 mg/dl, P = 0.401). The patients experienced complete resolution or noticeable reduction of ascites (P < 0.001), significant reduction of liver size (16.7 ± 2.2 vs. 13.7 ± 1.7 cm, P = 0.018), and significant enlargement of the portal trunk (10.7 ± 2.5 vs. 13.4 ± 2.4 mm, P = 0.017) after TIPS compared to the pre-TIPS state. CONCLUSION: TIPS may offer a potentially useful treatment for the GS-related HSOS.
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Enfermedad Veno-Oclusiva Hepática , Derivación Portosistémica Intrahepática Transyugular , Medicamentos Herbarios Chinos , Enfermedad Veno-Oclusiva Hepática/etiología , Humanos , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Eleven compounds, including nine known flavonoid glycosides (1-4, 6-8, and 10-11), one isoflavone glycoside (5), and a glansreginic acid (9), were isolated from the 80% ethanol extract of commercial Astragali Complanati Semen (ACS). All chemical structures were determined by spectroscopic analyses, including 1D and 2D NMR. Compounds 2, 4, 5, 6, 9, and 10 were isolated and identified from the title plant for the first time. Biological evaluation revealed that all the isolates showed promising anti-NO production, and 1, 2, 3, and 8 were more potent in antioxidant activity than vitamin E. The major peaks in the UPLC and HPLC profiles identified their chemical structures by comparing their retention time and UV spectra with those of the reference substances. Furthermore, nine of the eleven samples collected from North, Middle, and South regions of Taiwan possessed similar HPLC fingerprints and were identified as Astragali Complanati Semen, whereas the other two samples from southern Taiwan would be the adulterants due to the different fingerprinting patterns. In addition, an HPLC-UV method was employed to determine the content of target compound complanatuside (11) with good linear regression (R2 = 0.9998) for ACS in the Taiwanese market. Of the isolates, flavonol glycosides 1 and 3 were the major peaks in HPLC/UPLC, and showed more potent antioxidant and anti-NO production activities than that of 11, revealing that these compounds can be the available agents for the quality control of ACS.
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Planta del Astrágalo/química , Medicamentos Herbarios Chinos/química , Flavonoides/química , Extractos Vegetales/química , Antioxidantes/química , Antioxidantes/farmacología , Cromatografía Líquida de Alta Presión , Medicamentos Herbarios Chinos/farmacología , Flavonoides/farmacología , Glicósidos/química , Glicósidos/farmacología , Isoflavonas/química , Extractos Vegetales/farmacología , Control de Calidad , Semillas/química , TaiwánRESUMEN
Vitamin B6 is necessary to maintain normal metabolism and immune response, especially the anti-inflammatory immune response. However, the exact mechanism by which vitamin B6 plays the anti-inflammatory role is still unclear. Here, we report a novel mechanism of preventing excessive inflammation by vitamin B6 via reduction in the accumulation of sphingosine-1-phosphate (S1P) in a S1P lyase (SPL)-dependent manner in macrophages. Vitamin B6 supplementation decreased the expression of pro-inflammatory cytokines by suppressing nuclear factor-κB and mitogen-activated protein kinases signalling pathways. Furthermore, vitamin B6-reduced accumulation of S1P by promoting SPL activity. The anti-inflammatory effects of vitamin B6 were inhibited by S1P supplementation or SPL deficiency. Importantly, vitamin B6 supplementation protected mice from lethal endotoxic shock and attenuated experimental autoimmune encephalomyelitis progression. Collectively, these findings revealed a novel anti-inflammatory mechanism of vitamin B6 and provided guidance on its clinical use.
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Aldehído-Liasas/metabolismo , Inflamación/metabolismo , Lisofosfolípidos/metabolismo , Macrófagos/metabolismo , Esfingosina/análogos & derivados , Vitamina B 6/metabolismo , Animales , Antiinflamatorios/farmacología , Progresión de la Enfermedad , Encefalomielitis Autoinmune Experimental/metabolismo , Lipopolisacáridos/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Choque/metabolismo , Transducción de Señal , Esfingosina/metabolismoRESUMEN
Seven new cucurbitane-type triterpenoids, kuguaovins A-G (1-7), and five known ones were isolated from the rattans of wild Momordica charantia. Their structures were established by spectroscopic data analyses, including 1D and 2D NMR, IR, and MS techniques. The absolute configurations of the cucurbitanes were determined from NOESY data and partially by X-ray crystallographic analysis. In pharmacological studies, compounds 1-7 and 9-12 exhibited weak anti-inflammatory effects (IC50 = 15-35 µM), based on an anti-NO production assay.
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Antiinflamatorios no Esteroideos/farmacología , Glicósidos/farmacología , Momordica charantia/química , Extractos Vegetales/farmacología , Triterpenos/farmacología , Animales , Línea Celular Tumoral , Ensayos de Selección de Medicamentos Antitumorales , Espectroscopía de Resonancia Magnética , Espectrometría de Masas , Ratones , Estructura Molecular , Óxido Nítrico/antagonistas & inhibidores , Óxido Nítrico/biosíntesis , Extractos Vegetales/química , Células RAW 264.7 , Espectrofotometría Infrarroja , Difracción de Rayos XRESUMEN
The limited efficacy of "smart" nanotheranostic agents in eradicating tumors calls for the development of highly desirable nanoagents with diagnostics and therapeutics. Herein, to surmount these challenges, we constructed an intelligent nanoregulator by coating a mesoporous carbon nitride (C3N4) layer on a core-shell nitrogen-doped graphene quantum dot (N-GQD)@hollow mesoporous silica nanosphere (HMSN) and decorated it with a P-PEG-RGD polymer, to achieve active-targeting delivery (designated as R-NCNP). Upon irradiation, the resultant R-NCNP nanoregulators exhibit significant catalytic breakdown of water molecules, causing a sustainable elevation of oxygen level owing to the C3N4 shell, which facilitates tumor oxygenation and relieves tumor hypoxia. The generated oxygen bubbles serve as an echogenic source, triggering tissue impedance mismatch, thereby enhancing the generation of an echogenicity signal, making them laser-activatable ultrasound imaging agents. In addition, the encapsulated photosensitizers and C3N4-layered photosensitizer are simultaneously activated to maximize the yield of ROS, actualizing a triple-photosensitizer hybrid nanosystem exploited for enhanced PDT. Intriguingly, the N-GQDs endow the R-NCNP nanoregulator with a photothermal effect for hyperthemia, making it exhibit considerable photothermal outcomes and infrared thermal imaging (IRT). Importantly, further analysis reveals that the polymer-modified R-NCNPs actively target specific tumor tissues and display a triple-modal US/IRT/FL imaging-assisted cooperative PTT/PDT for real-time monitoring of tumor ablation and therapeutic evaluation. The rational synergy of triple-model PDT and efficient PTT in the designed nanoregulator confers excellent anticancer effects, as evidenced by in vitro and in vivo assays, which might explore more possibilities in personalized cancer treatment.
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Nanopartículas , Fotoquimioterapia , Línea Celular Tumoral , Rayos Láser , Nitrilos , Imagen Óptica , Fototerapia , Medicina de Precisión , Nanomedicina Teranóstica , Ultrasonografía , AguaRESUMEN
Bupleurum polysaccharides (BPs) is isolated from Bupleurum smithii var. parvifolium, a key traditional Chinese medicine. The study was to investigate the effects of BPs on diabetic kidney injury. After two intraperitoneal injections of streptozotozin (STZ) 100 mg·kg-1, renal injury in diabetic mice was induced and BPs was orally administrated at dosages of 30 and 60 mg·kg-1·d-1. The STZ injected mice developed renal function damage, renal inflammation and fibrosis known as diabetic kidney disease (DKD). BPs significantly reduced serum creatinine level and urinary albumin excretion rate, with the attenuated swelling of kidneys. BPs treatment obviously alleviated the pathological damage of renal tissue. The progression of renal injury in BPs treated mice was inhibited with less expression of type IV collagen (Col IV), fibronectin (FN) and α-smooth muscle actin (α-SMA). The inhibition of inflammation in kidney was associated with the reduced level of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). BPs administration suppressed the over-expression of toll like receptor 4 (TLR4) and high-mobility group box 1 (HMGB1) with lowered activity of nuclear factor kappa B (NF-κB) in renal tissue of diabetic mice. Oral administration of BPs effectively prevented the development ofrenal injury in diabetic mice. This study suggested that the protection provided by BPs might affect through the interruption of HMGB1-TLR4 pathway, leading to the inhibition of renal inflammation and fibrotic process.
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Bupleurum/química , Diabetes Mellitus Experimental/tratamiento farmacológico , Nefropatías Diabéticas/tratamiento farmacológico , Proteína HMGB1/metabolismo , Polisacáridos/uso terapéutico , Receptor Toll-Like 4/metabolismo , Animales , Citocinas/metabolismo , Diabetes Mellitus Experimental/inducido químicamente , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patología , Nefropatías Diabéticas/inducido químicamente , Nefropatías Diabéticas/metabolismo , Nefropatías Diabéticas/patología , Medicamentos Herbarios Chinos/administración & dosificación , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Inflamación/metabolismo , Inflamación/prevención & control , Riñón/efectos de los fármacos , Riñón/metabolismo , Riñón/patología , Masculino , Ratones Endogámicos C57BL , Raíces de Plantas/química , Polisacáridos/administración & dosificación , Polisacáridos/farmacología , Transducción de Señal/efectos de los fármacos , Estreptozocina/toxicidad , Factor de Transcripción ReIA/metabolismoRESUMEN
Six new dammarane-type saponins, gypenosides CP1-6 (16), along with 19 known compounds 7â»25, were isolated and characterized from the aerial parts of Gynostemma pentaphyllum. Among these compounds, eight dammarane-type saponins, 2, 5, 6, 7, 11, 12, 13, and 15, exhibited the greatest antiproliferative effects against two human tumor cell lines (A549 and HepG2).
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Antineoplásicos Fitogénicos/aislamiento & purificación , Gynostemma/química , Saponinas/aislamiento & purificación , Células A549 , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/farmacología , Proliferación Celular/efectos de los fármacos , Células Hep G2 , Humanos , Estructura Molecular , Componentes Aéreos de las Plantas/química , Extractos Vegetales/química , Saponinas/química , Saponinas/farmacología , Triterpenos , DamaranosRESUMEN
Engineering a versatile oncotherapy nanoplatform integrating both diagnostic and therapeutic functions has always been an intractable challenge in targeted cancer treatment. Herein, to actualize the theme of precise medicine, a nanoplatform is developed by anchoring Mn-Cdots to doxorubicin (DOX)-loaded mesoporous silica-coated gold cube-in-cubes core/shell nanocomposites and further conjugating them to a Arg-Gly-Asp (RGD) peptide (denoted as RGD-CCmMC/DOX) to achieve an active-targeting effect. Under 635 nm irradiation, the nanoplatform acts as oxygen nanogenerator that produces O2 in situ and amplifies the content of singlet oxygen (1O2) in the hypoxic tumor microenvironment (TME), which has been demonstrated to attenuate tumor hypoxia and synchronously enhance photodynamic efficacy. Moreover, the gold cube-in-cube core in this work has been proven as a photothermal agent for hyperthermia, which exhibits a favorable photothermal effect with a 65.6% calculated photothermal conversion efficiency under 808 nm irradiation. In addition, the nanoplatform achieves heat- and pH-sensitive drug release with precise control to specific-tumor sites, executing combined chemo-phototherapy functions. Besides, it functions as a multimodal bioimaging agent of photothermal, fluorescence, and magnetic resonance imaging for the accurate diagnosis and guidance of therapy. As validated by in vivo and in vitro assays, the TME-responsive nanoplatform is highly biocompatible and effectively obliterates 4T1 tumor xenografts on nude mice after triple-synergetic treatment. This work presents a rational design of versatile nanoplatforms, which modulate the TME to enable high therapeutic performance and multiplexed imaging, which provides an innovative paradigm for targeted tumor therapy.
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Neoplasias de la Mama/tratamiento farmacológico , Doxorrubicina/farmacología , Nanopartículas/química , Nanomedicina Teranóstica , Animales , Neoplasias de la Mama/patología , Doxorrubicina/química , Sistemas de Liberación de Medicamentos , Femenino , Oro/química , Xenoinjertos , Humanos , Células MCF-7 , Ratones , Péptidos/química , Péptidos/farmacología , Hipoxia Tumoral/efectos de los fármacos , Microambiente Tumoral/efectos de los fármacosRESUMEN
Cinobufotalin is a chemical compound extracted from the skin of dried bufo toads that may have curative potential for certain malignancies through different mechanisms; however, these mechanisms remain unexplored in breast cancer. The aim of the present study was to investigate the antitumor mechanism of cinobufotalin in breast cancer by using microarray data and in silico analysis. The microarray data set GSE85871, in which cinobufotalin exerted influences on the MCF7 breast cancer cells, was acquired from the Gene Expression Omnibus database, and the differentially expressed genes (DEGs) were analyzed. Subsequently, protein interaction analysis was conducted, which clarified the clinical significance of core genes, and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes were used to analyze cinobufotalinrelated pathways. The Connectivity Map (CMAP) database was used to select existing compounds that exhibited curative properties similar to those of cinobufotalin. A total of 1,237 DEGs were identified from breast cancer cells that were treated with cinobufotalin. Two core genes, SRC protooncogene nonreceptor tyrosine kinase and cyclindependent kinase inhibitor 2A, were identified as serving a vital role in the onset and development of breast cancer, and their expression levels were markedly reduced following cinobufotalin treatment as detected by the microarray of GSE85871. It also was revealed that the 'neuroactive ligandreceptor interaction' and 'calcium signaling' pathways may be crucial for cinobufotalin to perform its functions in breast cancer. Conducting a matching search in CMAP, miconazole and cinobufotalin were indicated to possessed similar molecular mechanisms. In conclusion, cinobufotalin may serve as an effective compound for the treatment of a subtype of breast cancer that is triple positive for the presence of estrogen, progesterone and human epidermal growth factor receptor2 receptors, and its mechanism may be related to different pathways. In addition, cinobufotalin is likely to exert its antitumor influences in a similar way as miconazole in MCF7 cells.
Asunto(s)
Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Bufanólidos/farmacología , Perfilación de la Expresión Génica , Transducción de Señal/efectos de los fármacos , Transcriptoma , Neoplasias de la Mama/patología , Caspasa 3/metabolismo , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Células MCF-7 , ProteolisisRESUMEN
Phytochemical investigation of ethanol extracts from two Taiwanese collections of Vernonia cinerea resulted in the isolation of eighteen hirsutinolide-type sesquiterpenoids, including seven new ones designated as vernolides Eâ-âK (1: -7: ). All structures were determined by a combination of detailed spectroscopic analyses (NMR and MS) and comparison with reported data. In an in vitro anti-inflammatory assay, compounds 3, 7, 9, 11: , and 14: exhibited strong inhibitory activities toward NO production by LPS-induced RAW264.7 macrophages, with IC50 values of 1.18, 0.85, 0.66, 0.71 and 0.45 µM, respectively, without affecting cellular viability at 40 µM. Preliminary structure-activity relationships indicate that the ester groups at C-8 and C-13 may enhance inhibition of NO production.