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CII-3 is the effective part of Periplaneta americana for application in oncotherapy. This study investigated its main chemical components for macrophage polarization regulation activity. Compounds were separated and purified, and their structures were elucidated based on NMR and HR-ESI-MS analyses. After inducing the M1 and M2 phenotype macrophages, CII-3 and testing components were added and co-incubated to evaluate their effects on the relevant markers of macrophages. Then, gradient concentrations of CII-3 and active monomers were further investigated for their effects on M2 macrophages. The effects were detected by RT-PCR, ELISA, flow cytometry, and immunofluorescence. Twelve compounds were identified from CII-3. CII-3 and pericanaside (5) had no obvious effect on M1 macrophages, while they significantly reduced the expression levels of M2 macrophage markers. Specifically, they significantly reduced the levels of TGF-ß and IL-10 and the mRNA expression levels of ARG-1 and CD206 in the M2 phenotypes of RAW264.7 and Ana-1 macrophages. The conditioned medium of CII-3 and pericanaside (5) could inhibit the migration capacity of CT26.WT tumor cells. Macrophage M1/M2 polarization is a dynamic equilibrium, and the M2 phenotype, which can promote the growth of tumor cells, is relatively highly expressed in the tumor microenvironment. CII-3 and pericanaside could significantly reduce the phenotype of M2-type macrophages, indicating that the anti-tumor activity of CII-3 could be related to the inhibitory effect on M2 polarization, and pericanaside was one of the active components.
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Periplaneta , Animales , Biomarcadores/metabolismo , Activación de Macrófagos , Macrófagos , FenotipoRESUMEN
CONTEXT: Acute ischaemic stroke (AIS) is a major cause of disability and death, which is a serious threat to human health and life. Wasp venom extracted from Vespa magnifica Smith (Vespidae) could treat major neurological disorders. OBJECTIVE: This study investigated the effects of wasp venom on AIS in rats. MATERIAL AND METHODS: We used a transient middle cerebral artery occlusion (MCAO) model in Sprague-Dawley rats (260-280 g, n = 8-15) with a sham operation group being treated as negative control. MCAO rats were treated with wasp venom (0.05, 0.2 and 0.6 mg/kg, i.p.) using intraperitoneal injection. After treatment 48 h, behavioural tests, cortical blood flow (CBF), TTC staining, H&E staining, Nissl staining, TUNEL assay, immunohistochemistry (IHC) and ELISA were employed to investigate neuroprotective effects of wasp venom. RESULTS: Compared with the MCAO group, wasp venom (0.6 mg/kg) improved neurological impairment, accelerated CBF recovery (205.6 ± 52.92 versus 216.7 ± 34.56), reduced infarct volume (337.1 ± 113.2 versus 140.7 ± 98.03) as well as BBB permeability as evidenced by changes in claudin-5 and AQP4. In addition, function recovery of stroke by wasp venom treatment was associated with a decrease in TNF-α, IL-1ß, IL-6 and inhibition activated microglia as well as apoptosis. Simultaneously, the wasp venom regulated the angiogenesis factors VEGF and b-FGF in the brain. CONCLUSIONS: Wasp venom exhibited a potential neuroprotective effect for AIS. In the future, we will focus on determining whether the observed actions were due to a single compound or the interaction of multiple components of the venom.
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Isquemia Encefálica/tratamiento farmacológico , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Fármacos Neuroprotectores/farmacología , Venenos de Avispas/farmacología , Animales , Apoptosis/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Infarto de la Arteria Cerebral Media , Masculino , Neuronas/efectos de los fármacos , Neuronas/patología , Fármacos Neuroprotectores/administración & dosificación , Ratas , Ratas Sprague-Dawley , Venenos de Avispas/administración & dosificación , AvispasRESUMEN
BACKGROUNDS: Although the physical and mental enhancement effect of essential oils have been proved, the beneficial effect of essential oil in central fatigue remains unclear. In this study, we extracted essential oils from nine aromatic plants to make a compound essential oil, and detected the therapeutic effect of central fatigue by daily aerial diffusion. METHODS: Thirty-three rats were randomly and equally divided into control group, chronic sleep deprivation group, and compound essential oil inhalation group. Central fatigue was generated by chronic sleep deprivation. RESULTS: After 21-day various interferences, it is found that the sleep deprivation rats showed an evident decrease in physical endurance, negative emotion, and cognitive dysfunction compared with the control group, and the group that treated with the compound essential oil behaved significantly better than central fatigue group. CONCLUSION: We concluded that this formula of essential oils could alleviate central fatigue on rats, and our study provides a new direction of application of aromatic therapy, which could be expanded to insomnia, depression and other healthy issue in the further research.
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Fatiga/tratamiento farmacológico , Aceites Volátiles/administración & dosificación , Aceites de Plantas/administración & dosificación , Administración por Inhalación , Animales , Fatiga/fisiopatología , Humanos , Masculino , Aceites Volátiles/química , Aceites de Plantas/química , Ratas , Ratas Wistar , Sueño , Trastornos del Inicio y del Mantenimiento del Sueño/tratamiento farmacológico , Trastornos del Inicio y del Mantenimiento del Sueño/fisiopatologíaRESUMEN
Five new phenolic compounds rynchopeterines A-E (1-5), in addition to thirteen known phenolics, were isolated from Blaps rynchopetera Fairmaire, a kind of medicinal insect utilized by the Yi Nationality in Yunnan Province of China. Their structures were established on the basis of extensive spectroscopic analyses (1D and 2D NMR, HR-MS, IR) along with calculated electronic circular dichroism method. Rynchopeterines A-E (1-4) exhibited significant antioxidant activities with IC50 values of 7.67-12.3 µg/mL measured by the 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. Besides, rynchopeterines B (2) and C (3) showed mild cytotoxicity against tumor cell Caco-2 and A549.
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Antineoplásicos , Antioxidantes , Escarabajos/química , Hidroxibenzoatos , Neoplasias/tratamiento farmacológico , Células A549 , Animales , Antineoplásicos/química , Antineoplásicos/aislamiento & purificación , Antineoplásicos/farmacología , Antioxidantes/química , Antioxidantes/aislamiento & purificación , Antioxidantes/farmacología , Células CACO-2 , Humanos , Hidroxibenzoatos/química , Hidroxibenzoatos/aislamiento & purificación , Hidroxibenzoatos/farmacología , Neoplasias/metabolismo , Neoplasias/patologíaRESUMEN
Blaps rynchopetera Fairmaire has long been used as a folk medicine by the Yi and Bai ethnic groups in China to treat fever, cough, gastritis, boils, and tumors. In the present study, the cytotoxicity of the defensive secretion (TDS) of B. rynchopetera against AGS Caco-2, HepG2 U251 and Bel-7402 was tested, and the results revealed that TDS had potent cytotoxicity against testing cells with IC50 values of 45.8, 17.4, 53.6, 98.4 and 23.4 µg/mL, respectively. Gas chromatography-mass spectrometry (GC-MS) analysis was employed to clarify the cytotoxic constituents in TDS of B. rynchopetera and five volatile compounds, including 2-ethyl-2,5-cyclohexadiene-1,4-dione (3, 31.00%), 1-tridecene (5, 28.02%), 2-methyl-2,5-cyclohexadiene-1,4-dione (2, 22.86%), hydroquinone (4, 1.33%), and p-benzoquinone (1, 1.01%), were identified. Chemical constituent investigation on TDS further supported the presence of 5 above compounds. A cytotoxic assay indicated that compounds 1, 2, 3 and 4 exhibited significant cytotoxicity against the testing cell lines, implying that benzoquinones and hydroquinone played important roles in the cytotoxicity of TDS of B. rynchopetera. TDS is a cytotoxic natural material and further studies investigating mechanisms and inhibitory activities on other cell lines is warranted.
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Antineoplásicos/química , Secreciones Corporales/química , Compuestos Orgánicos Volátiles/química , Alquenos/química , Alquenos/farmacología , Animales , Antineoplásicos/farmacología , Benzoquinonas/química , Benzoquinonas/farmacología , Línea Celular Tumoral , Supervivencia Celular , Escarabajos , Ciclohexenos/química , Ciclohexenos/farmacología , Humanos , Hidroquinonas/química , Hidroquinonas/farmacología , Estructura Molecular , Compuestos Orgánicos Volátiles/farmacologíaRESUMEN
The feasibility was investigated for identifying sound, yellow and citrus greening leaves of navel orange trees based on hyperspectral imaging combined with correlation analysis and discriminant partial least square (DPLS) methods. The hyperspectral data of sound, yellow and citrus greening leaves were recorded in the wavelength range of 374.28ï½1 016.89 nm. Two regions of interest (ROI) were marked symmetrically on both sides along main veins with an ellipse of major axis of 60 pixels and minor axis of 30 pixels. The average reflectance spectrum was extracted from ROI regions. A pair wavelengths of 502.79 and 374.28 nm were chosen with correlation analysis method in the wavelength range of 374.28ï½1 016.89 nm. The classification model was developed with the peak ratio of the pair wavelengths. This model was effective to sound leaves with the recognition accuracy of 1.7% but yellow and citrus greening leaves. The DPLS model was employed with the preprocessing spectra of second derivative and Savitzky-Golay smoothing. The recognition accuracy of this model was 100% for citrus greening leaves and yellow ones. The number of latent variables (LVs) was optimized with the leave one out cross validation method. The optimal LVs, correlation coefficient and standard error of calibration of the DPLS model were 17, 0.96 and 0.13, respectively. The correction classification rate of the DPLS model was 100% for yellow leaves and citrus greening ones. Two-step method of the peak ratio models combination with the DPLS was proposed for identifying sound, yellow and citrus greening leaves. The new samples were applied to evaluation the classification ability of the two-step method, which included sound leaves of 10, citrus greening leaves of 10 and yellow leaves of 10. The correction classification rate reached 96.7%. Experimental results showed that it was feasible to identify sound, yellow and citrus greening leaves by hyperspectral imaging coupled with the peak ratio and DPLS models.
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Citrus sinensis , Calibración , Color , Análisis de los Mínimos Cuadrados , Hojas de la Planta , Espectroscopía Infrarroja CortaRESUMEN
Mouse bone marrow-derived Lin(-)-Sca-1(+) endothelial progenitor cell (EPC) has pluripotent abilities such as supporting neovascularization. Vascular endothelial growth factor (VEGF) receptor 1 (VEGFR1) (Flt1) recognizes various VEGF isoforms and is critically implicated in a wide range of physiological and pathological settings, including vasculogenesis. Mouse EPC expresses two isoforms of VEGFR1: mFlt1, which transmits ligand-induced signals; and sFlt1, which acts as a negative regulator by sequestering ligands of VEGF receptors. How the relative levels of mFlt1 and sFlt1 are regulated is not yet clear. We report here that tumor necrosis factor superfamily 15 (TNFSF15) (also known as VEGI or TL1A), an endothelial cell-secreted cytokine, simultaneously promotes mFlt1 degradation and up-regulates sFlt1 expression in EPC, giving rise to disruption of VEGF- or PlGF-induced activation of eNOS and MAPK p38 and effective inhibition of VEGF-driven, EPC-supported vasculogenesis in a murine Matrigel implant model. TNFSF15 treatment of EPC cultures facilitates Akt deactivation-dependent, ubiquitin-assisted degradation of mFlt1 and stimulates sFlt1 expression by activating the PKC, Src, and Erk1/2 signaling pathway. Additionally, TNFSF15 promotes alternative splicing of the Flt1 gene in favor of sFlt1 production by down-regulating nuclear protein Jumonji domain-containing protein 6 (Jmjd6), thus alleviating Jmjd6-inhibited sFlt1 expression. These findings indicate that TNFSF15 is a key component of a molecular mechanism that negatively modulates EPC-supported vasculogenesis through regulation of the relative levels of mFlt1 and sFlt1 in EPC.
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Regulación de la Expresión Génica/fisiología , Neovascularización Fisiológica/fisiología , Proteolisis , Miembro 15 de la Superfamilia de Ligandos de Factores de Necrosis Tumoral/fisiología , Receptor 1 de Factores de Crecimiento Endotelial Vascular/metabolismo , Empalme Alternativo/fisiología , Análisis de Varianza , Animales , Western Blotting , Colágeno , Combinación de Medicamentos , Células Endoteliales/metabolismo , Laminina , Ligandos , Ratones , Microscopía Fluorescente , Isoformas de Proteínas/metabolismo , Proteoglicanos , Células Madre/metabolismo , Miembro 15 de la Superfamilia de Ligandos de Factores de Necrosis Tumoral/metabolismoRESUMEN
Objective: To study the chemical constituents of Swertia binchuanensis. Methods: The constituents were separated and purifyed by conventional methods. Their structures were identified on the basis of spectral analysis such as 1H-NMR,13C-NMR. Results: Seven compounds were isolated and identified as 1, 2, 3, 4-tetrahydro-1, 4, 8-trihydroxy-6-methoxyxanhoneï¼ â ï¼, erythrocentaurinï¼ â ¡ï¼,1-O-ß-D-glucopyranosyl-1, 2, 3, 4-tetrahydro-4, 8-dihydroxy-6-methoxyxanthoneï¼ â ¢ï¼, maslinic acidï¼ â £ï¼,1-hydroxy-3, 7-dimethoxyxanthoneï¼ â ¤ï¼,1, 8-dihydroxy-3, 5-dimethoxyxanthoneï¼ â ¥ï¼,1, 7-dihydroxy-3, 4, 8-termethoxyxanthoneï¼ â ¦ï¼. Conclusion: All compounds were isolated from Swertia binchuanensis for the first time.
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Swertia , Medicamentos Herbarios Chinos , Flavonoides , Estructura Molecular , TriterpenosRESUMEN
BACKGROUND: Pheophorbide a oxygenase (PAO) is an important enzyme in the chlorophyll catabolism pathway and is involved in leaf senescence. It opens the porphyrin macrocycle of pheophorbide a and finally forms the primary fluorescent chlorophyll catabolite. Previous studies have demonstrated the function of PAO during cell death. However, the characterizaton of PAO during leaf senescence induced by environmental factors is not well understood. METHODS: Homology-based cloning and RACE techniques were used to obtain the full-length cDNA of the CaPAO gene. CaPAO expression was determined by quantitative real-time PCR. Function of CaPAO gene were studied using virus-induced gene silencing and transgenic techniques with tobacco plants (Nicotiana tabacum). RESULTS: A novel PAO gene CaPAO was isolated from pepper (Capsicum annuum L.). The full-length CaPAO cDNA is comprised of 1838 bp, containing an open reading frame of 1614 bp, and encodes a 537 amino acid protein. This deduced protein belongs to the Rieske-type iron-sulfur superfamily, containing a conserved Rieske cluster. CaPAO expression, as determined by quantitative real-time PCR, was higher in leaves than roots, stems and flowers. It was upregulated by abscisic acid, methyl jasmonate and salicylic acid. Moreover, CaPAO was significantly induced by high salinity and osmotic stress treatments and also was regulated by Phytophthora capsici. The virus-induced gene silencing technique was used to silence the CaPAO gene in pepper plants. After 3 days of high salt treatment, the chlorophyll breakdown of CaPAO-silenced pepper plants was retarded. RD29A promoter-inducible expression vector was constructed and transferred into tobacco plant. After 7 days of salt treatment, the leaves of transgenic plants were severely turned into yellow, the lower leaves showed necrotic symptom and chlorophyll content was significantly lower than that in the control plants. CONCLUSIONS: The expression of CaPAO gene was induced in natural senescence and various stresses. The CaPAO gene may be related to defense responses to various stresses and play an important role in salt-induced leaf senescence.
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Capsicum/genética , Oxigenasas/genética , Hojas de la Planta/fisiología , Proteínas de Plantas/genética , Tolerancia a la Sal/genética , Secuencia de Aminoácidos , Capsicum/enzimología , Clonación Molecular , Datos de Secuencia Molecular , Oxigenasas/química , Oxigenasas/metabolismo , Filogenia , Proteínas de Plantas/química , Proteínas de Plantas/metabolismo , Plantas Tolerantes a la Sal/genética , Alineación de Secuencia , Nicotiana/genética , Nicotiana/fisiologíaRESUMEN
BACKGROUND: Growing body of laboratory evidence supports the beneficial effects of n-3 polyunsaturated fatty acids (PUFAs) on colorectal cancer (CRC) prevention. Epidemiologic studies investigating the relationship between n-3 PUFAs intake and risk of CRC, however, have been inconsistent. We aimed to clarify the relation by conducting a meta-analysis of prospective studies. METHODS: Eligible studies were identified by searching PubMed database and by carefully reviewing bibliographies of retrieved publications. Summary relative risks (RRs) with their 95 % confidence intervals (CIs) were computed with a random-effects model. Subgroup, meta-regression, and dose-response analyses were performed to explore potential sources of heterogeneity. RESULTS: A total of 14 prospective studies involving 8,775 cancer cases were included in the final analysis. Overall, total n-3 or marine PUFAs intake was not associated with risk of CRC (RR 0.99 and 1.00). However, there was a trend toward reduced risk of proximal colon cancer (total n-3 PUFAs: RR 0.83, 95 % CI 0.66-1.05; marine PUFAs: RR 0.81, 95 % CI 0.59-1.10) and a significant increased risk of distal colon cancer (total n-3 PUFAs: RR 1.26, 95 % CI 1.06-1.50; marine PUFAs: RR 1.38, 95 % CI 1.11-1.71). Furthermore, marine PUFAs intake accessed longer before diagnosis was associated 21 % reduced risk of CRC (RR 0.79, 95 % CI 0.63-1.00). CONCLUSION: Overall, this meta-analysis finds no relation between n-3 PUFAs intake and risk of CRC. The observed subsite heterogeneity within colon cancer and the possible effect modification by latency time merit further studies.
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Neoplasias Colorrectales/epidemiología , Grasas de la Dieta/administración & dosificación , Ácidos Grasos Omega-3/administración & dosificación , Neoplasias Colorrectales/etiología , Neoplasias Colorrectales/prevención & control , Femenino , Humanos , Masculino , Estudios Prospectivos , Factores de RiesgoRESUMEN
Cysteine proteinases have been known to participate in developmental processes and in response to stress in plants. Our present research reported that a novel CP gene, CaCP, was involved in leaf senescence in pepper (Capsicum annuum L.). The full-length CaCP cDNA is comprised of 1316 bp, contains 1044 nucleotides in open reading frame (ORF), and encodes a 347 amino acid protein. The deduced protein belongs to the papain-like cysteine proteases (CPs) superfamily, containing a highly conserved ERFNIN motif, a GCNGG motif and a conserved catalytic triad. This protein localized to the vacuole of plant cells. Real-time quantitative PCR analysis revealed that the expression level of CaCP gene was dramatically higher in leaves and flowers than that in roots, stems and fruits. Moreover, CaCP transcripts were induced upon during leaf senescence. CaCP expression was upregulated by plant hormones, especially salicylic acid. CaCP was also significantly induced by abiotic and biotic stress treatments, including high salinity, mannitol and Phytophthora capsici. Loss of function of CaCP using the virus-induced gene-silencing technique in pepper plants led to enhanced tolerance to salt- and osmotic-induced stress. Taken together, these results suggest that CaCP is a senescence-associated gene, which is involved in developmental senescence and regulates salt- and osmotic-induced leaf senescence in pepper.
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Capsicum/fisiología , Proteasas de Cisteína/genética , Presión Osmótica , Hojas de la Planta/fisiología , Proteínas de Plantas/genética , Secuencia de Aminoácidos , Capsicum/química , Capsicum/genética , Proteasas de Cisteína/química , ADN Complementario/genética , Regulación de la Expresión Génica de las Plantas , Silenciador del Gen , Datos de Secuencia Molecular , Hojas de la Planta/química , Hojas de la Planta/genética , Proteínas de Plantas/química , Alineación de SecuenciaRESUMEN
Both the gene expression and activity of water channel protein can control transmembrane water movement. We have reported the overexpression of CaTIP1-1, which caused a decrease in chilling tolerance in transgenic plants by increasing the size of the stomatal pore. CaTIP1-1 expression was strongly induced by salt and mannitol stresses in pepper (Capsicum annuum). However, its biochemical and physiological functions are still unknown in transgenic tobacco. In this study, transient expression of CaTIP1-1-GFP in tobacco suspension cells revealed that the protein was localized in the tonoplast. CaTIP1-1 overexpressed in radicle exhibited vigorous growth under high salt and mannitol treatments more than wild-type plants. The overexpression of CaTIP1-1 pepper gene in tobacco enhanced the antioxidant enzyme activities and increased transcription levels of reactive oxygen species-related gene expression under osmotic stresses. Moreover, the viability of transgenic tobacco cells was higher than the wild-type after exposure to stress. The pepper plants with silenced CaTIP1-1 in P70 decreased tolerance to salt and osmotic stresses using the detached leaf method. We concluded that the CaTIP1-1 gene plays an important role in response to osmotic stresses in tobacco.
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Capsicum/genética , Genes de Plantas , Nicotiana/genética , Nicotiana/fisiología , Presión Osmótica , Proteínas de Plantas/genética , Estrés Fisiológico/genética , Antioxidantes/metabolismo , Capsicum/enzimología , Capsicum/fisiología , Catalasa/metabolismo , Muerte Celular , Supervivencia Celular , Electrólitos/metabolismo , Regulación de la Expresión Génica de las Plantas , Silenciador del Gen , Malondialdehído/metabolismo , Peroxirredoxinas/metabolismo , Fenotipo , Hojas de la Planta/metabolismo , Proteínas de Plantas/metabolismo , Plantas Modificadas Genéticamente , Transporte de Proteínas , ARN Mensajero/genética , ARN Mensajero/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Plantones/crecimiento & desarrollo , Fracciones Subcelulares/metabolismo , Superóxido Dismutasa/metabolismo , AguaRESUMEN
Wasps play important roles as predators and pollinators in the ecosystem. The Jingpo minority residing in Yunnan Province, China, has a traditional practice of using wine infused with mature wasps as a customary remedy for managing rheumatoid arthritis. The larva of the wasp is also a tasteful folk dish that has created a tremendous market. There is a paucity of survival knowledge, which has greatly restricted their potential applications in food and healthcare. Recent research has highlighted the importance of gut microbiota in insect growth. Nevertheless, there is still a lack of understanding regarding the composition, changes, and functions of the gut microbiota in Vespa mandarinia during development. In this research, the gut microbiota were investigated across three growth stages of Vespa mandarinia using a metagenomic technology. The result revealed that there are significant variations in the proportion of main gut microbes during the metamorphosis of Vespa mandarinia. Tenericutes were found to dominate during the larval stage, while Proteobacteria emerged as the dominant group post-pupation. Through a comprehensive analysis of the gut microbiota metagenome, this study revealed functional differences in the wasp gut microbiota at various growth stages. During the larval stage, the gut microbiota plays a central role in promoting metabolism. Following pupation, the gut microbiota exhibited diversified functions, likely due to the complex environments and diverse food sources encountered after metamorphosis. These functions included amino acid metabolism, compound degradation, and defense mechanisms. This research provides an extensive dataset on the gut microbiota during the metamorphosis of Vespa mandarinia, contributing to a deeper understanding of the influence of gut microbiota on wasp growth. Furthermore, this study uncovers a unique microbial treasure within insect guts, which is important for advancing the application of wasps in the fields of food and medicine.
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OBJECTIVE: To explore the proliferation inhibitory effect of quinones from Blaps rynchopetera defense secretion on colorectal tumor cell lines. METHODS: Human colorectal cancer cell HT-29, human colorectal adenocarcinoma cell Caco-2 and normal human colon epithelial cell CCD841 were chosen for the evaluation of inhibitory activity of the main quinones of B. rynchopetera defense secretion, including methyl p-benzoquinone (MBQ), ethyl p-benzoquinone (EBQ), and methyl hydroquinone (MHQ), through methyl thiazolyl tetrazolium assay. The tumor-related factors, cell cycles, related gene expressions and protein levels were detected by enzyme-linked immunosorbent assy, flow cytometry, RT-polymerase chain reaction and Western blot, respectively. RESULTS: MBQ, EBQ, and MHQ could significantly inhibit the proliferation of Caco-2, with half maximal inhibitory concentration (IC50) values of 7.04 ± 0.88, 10.92 ± 0.32, 9.35 ± 0.83, HT-29, with IC50 values of 14.90 ± 2.71, 20.50 ± 6.37, 13.90 ± 1.30, and CCD841, with IC50 values of 11.40 ± 0.68, 7.02 ± 0.44 and 7.83 ± 0.05 µg/mL, respectively. Tested quinones can reduce the expression of tumor-related factors tumor necrosis factor α, interleukin (IL)-10, and IL-6 in HT-29 cells, selectively promote apoptosis, and regulate the cell cycle which can reduce the proportion of cells in the G1 phase and increase the proportion of the S phase. Meanwhile, tested quinones could up-regulate mRNA and protein expression of GSK-3ß and APC, while down-regulate that of ß-catenin, Frizzled1, c-Myc, and CyclinD1 in the Wnt/ß-catenin pathway of HT-29 cells. CONCLUSION: Quinones from B. rynchopetera defense secretion could inhibit the proliferation of colorectal tumor cells and reduce the expression of related factors, which would be functioned by regulating cell cycle, selectively promoting apoptosis, and affecting Wnt/ß-catenin pathway-related mRNA and protein expressions.
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Neoplasias Colorrectales , beta Catenina , Humanos , beta Catenina/metabolismo , Células CACO-2 , Quinonas/farmacología , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Proliferación Celular , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Línea Celular Tumoral , Apoptosis , Benzoquinonas/farmacología , ARN Mensajero , Vía de Señalización WntRESUMEN
Two undescribed polyketides canecines A-B, one unreported cyclopentenone canecine C, together with 12 known compounds were isolated from an extract of the fungus Penicillium canescens DJJ-1. Their structures were elucidated by detailed analysis of spectroscopic data, NMR calculations with dJ-DP4 or DP4+, and their absolute configurations were further determined by quantum chemical calculations of ECD spectra or X-crystallography. Canecine A was a grisan polyketide featuring a dimethyltetrahydro-4H-furo[2,3-b]pyran. Canecine A exhibited significant inhibitory activity against Candida albicans with an MIC value of 1 µg/mL and showed inhibitory effect on nitric oxide production in LPS-activated RAW264.7 macrophages. These results enrich the structural diversities of polyketides from endophytic fungi.
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Antiinfecciosos , Penicillium , Policétidos , Estructura Molecular , Policétidos/química , Penicillium/química , Espectroscopía de Resonancia MagnéticaRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Rheumatoid arthritis (RA) is a chronic inflammatory disease that is related to the aberrant proliferation of fibroblast-like synoviocytes (FLS). Wasp venom (WV, Vespa magnifica, Smith), an insect secretion, has been used to treat RA in Chinese Jingpo national minority's ancient prescription. However, the potential mechanisms haven't been clarified. AIM OF THE STUDY: The purposes of this paper were two-fold. First, to investigate which was the best anti-RA effective part of WV-I (molecular weight less than 3 kDa), WV-II (molecular weight 3-10 kDa) and WV-III (molecular weight more than 10 kDa) that were separated from WV. Second, to explore the underlying molecular mechanism of WV and WV-II that was best effective part in RA. MATERIALS AND METHODS: The wasps were electrically stimulated and the secretions were collected. WV-I, WV-II and WV-III were acquired by ultracentrifuge method according to molecular weight. Next, WV, WV-I, WV-II and WV-III were identified by HPLC. Functional annotation and pathway analysis of WV used to bioinformatics analysis. RNA-seq analyses were constructed to identify differentially expressed genes (DEGs). GO and KEGG pathway analyses were performed by Metascape database. STRING was used to analyze the PPI network from DEGs. Next, PPI network was visualized using Cytoscape that based on MCODE. The pivotal genes of PPI network and MCODE analysis were verified by qRT-PCR. Subsequently, MH7A cells were performed by MTT assay to evaluate the ability of inhibiting cell proliferation. Luciferase activity assay was conducted in HepG2/STAT1 or HepG2/STAT3 cells to assess STAT1/3 sensitivity of WV, WV-I, WV-II and WV-III. Additionally, interleukin (IL)-1ß and IL-6 expression levels were detected by ELISA kits. Intracellular thioredoxin reductase (TrxR) enzyme was evaluated by TrxR activity assay kit. ROS levels, lipid ROS levels and Mitochondrial membrane potential (MMP) were assessed by fluorescence probe. Cell apoptosis and MMP were measured by using flow cytometry. Furthermore, the key proteins of JAK/STAT signaling pathway, protein levels of TrxR and glutathione peroxidase 4 axis (GPX4) were examined by Western blotting assay. RESULTS: RNA-sequencing analysis of WV displayed be related to oxidation-reduction, inflammation and apoptosis. The data displayed that WV, WV-II and WV-III inhibited significantly cells proliferation in human MH7A cell line compared to WV-I treatment group, but WV-III had no significant suppressive effect on luciferase activity of STAT3 compared with IL-6-induced group. Combined with earlier reports that WV-III contained major allergens, we selected WV and WV-II further to study the mechanism of anti-RA. In addition, WV and WV-II decreased the level of IL-1ß and IL-6 in TNF-α-induced MH7A cells via inactivating of JAK/STAT signaling pathway. On the other hand, WV and WV-II down-regulated the TrxR activity to produce ROS and induce cell apoptosis. Furthermore, WV and WV-II could accumulate lipid ROS to induce GPX4-mediated ferroptosis. CONCLUSIONS: Taken together, the experimental results revealed that WV and WV-II were potential therapeutic agents for RA through modulating JAK/STAT signaling pathways, redox homeostasis and ferroptosis in MH7A cells. Of note, WV-II was an effective part and the predominant active monomer in WV-II will be further explored in the future.
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Artritis Reumatoide , Ferroptosis , Sinoviocitos , Avispas , Animales , Humanos , Venenos de Avispas/farmacología , Venenos de Avispas/metabolismo , Venenos de Avispas/uso terapéutico , Interleucina-6/metabolismo , Avispas/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/metabolismo , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Proliferación Celular , Antioxidantes/farmacología , Oxidación-Reducción , Fibroblastos , Luciferasas , Lípidos/farmacología , Células CultivadasRESUMEN
In order to investigate the contamination levels of dust and its surrounding green land soil heavy metal pollution and potential ecological and health risks in the scenic areas of urban waterfront parks, the gardens, squares, and theme parks of the Yellow River Custom Tourist Line in Lanzhou were selected as the research area, using 27 dust samples and 26 soil samples from its surrounding green lands. The contamination characteristics and potential ecological risks of eight heavy metals (Cr, Ni, Cu, Zn, As, Cd, Hg, and Pb) were evaluated using the geo-accumulation index (Igeo), single-factor pollution index (Pi), Nemerow integrated pollution index (PN), and improved potential ecological risk index (RI). The human health risk assessment was also evaluated using the exposure risk model. The results showed that the average concentrations of the other heavy metals in the surface dusts were higher than the background values of Gansu Province and Lanzhou City, except that the As mean concentrations in the surface dusts and the surrounding green land soils were slightly lower than the Gansu Province background values. For its surrounding green land soils, the mean concentrations of the other heavy metals (Cu, Zn, Cd, Hg, and Pb) exceeded the soil background values of Gansu Province and Lanzhou City, whereas the Cr and Ni mean concentrations were lower than their corresponding soil background values of Gansu Province and Lanzhou City. The geo-accumulation and single-factor pollution indices demonstrated that a slight to moderate pollution of Cr, Cu, Zn, Cd, Hg, and Pb occurred in surface dusts, and Cu, Zn, Cd, Hg, and Pb appeared in varying degrees of contamination levels in its surrounding green land soils. The Nemerow integrated pollution index analysis manifested that the overall contamination status of the study areas was between slightly and heavily polluted. The potential ecological risk index suggested that Cd and Hg were recognized as significant pollutant elements and that the RI of the other heavy metals were all below 40, presenting slight ecological risk. The health risk assessment indicated that ingestion was the dominant exposure pathway for heavy metals from the surface dusts and the surrounding green land soils, and no carcinogenic and noncarcinogenic risks posed threats to adults and children.
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Mercurio , Metales Pesados , Adulto , Niño , Humanos , Cadmio , Plomo , Ríos , PolvoRESUMEN
Objectives: This study aimed to investigate the potential effects of wasp venom (WV) from Vespa magnifica on antithrombosis in rats with inferior vena cava (IVC) thrombosis. Materials and Methods: The thrombosis rat model was established by improving the IVC stenosis, in which rats were subjected to IVC ligation for 75 min. Rats were administered argatroban (IP) or WV (s.c.) for 4 hr after IVC thrombosis. The weight, inhibition rate, and pathological morphology of the thrombosis induced by IVC ligation and the variation in four coagulation parameters, coagulation factors, and CD61+CD62P+ were simultaneously determined in IVC rats. Results: The thrombus formed as a result of IVC ligation was stable. Compared with the control group, the weight of the thrombus was significantly reduced in the argatroban group. Thrombus weight was reduced by treatment with 0.6, 0.2, and 0.05 mg/kg WV, with inhibition rates of 52.19%, 35.32%, and 28.98%, respectively. Inflammatory cells adhered to and infiltrated the vessel wall in the IVC group more than in the sham group. However, the pathological morphology and CD61+CD62P+ of the WV treatment groups tended to be normal. Conclusion: We improved the model of IVC thrombosis to be suitable for evaluation of antithrombotic drugs. Our findings demonstrated that WV could inhibit IVC thrombosis associated with reducing coagulation factors V and CD61+CD62p expression in rats.
RESUMEN
PURPOSE: To investigate the effects of Periplaneta americana L. on ulcerative colitis (UC) induced by a combination of chronic stress (CS) and 2,4,6-trinitrobenzene sulfonic acid enema (TNBS) in rats. METHODS: The experiment UC model with CS was established in rats by a combination of chronic restraint stress, excess failure, improper, and TNBS. The body weight, disease activity index (DAI), colonic mucosal injury index (CMDI), histopathological score (HS) and pro-inflammatory mediators were measured. The content of corticotropin-releasing hormone (CRH) in hypothalamus or adrenocorticotropic hormone (ACTH) and corticosteroids (CORT) in plasma were evaluated by enzyme-linked immunosorbent assay. The proportion of T lymphocyte subsets was detected by flow cytometry, and gut microbiota was detected by 16S rDNA amplicon sequencing. RESULTS: Weight loss, DAI, CMDI, HS and proinflammatory mediators were reversed in rats by P. americana L. treatment after UC with CS. Increased epidermal growth factor (EGF) was observed in P. americana L. groups. In addition, P. americana L. could reduce the content of CRH and ACTH and regulate the ratio of CD3+, CD3+CD8+ and CD3+CD4+CD25+/CD4+ in spleen. Comparably, P. americana L. changes composition of gut microbiota. CONCLUSIONS: The ethanol extract of Periplaneta Americana L. improves UC induced by a combination of CS and TNBS in rats.
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Colitis Ulcerosa , Colitis , Periplaneta , Hormona Adrenocorticotrópica/metabolismo , Hormona Adrenocorticotrópica/farmacología , Hormona Adrenocorticotrópica/uso terapéutico , Animales , Colitis/patología , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/tratamiento farmacológico , Colon/patología , Modelos Animales de Enfermedad , Enema , Etanol/farmacología , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Ratas , Ácido Trinitrobencenosulfónico/metabolismoRESUMEN
PURPOSE: To explore the potential immunomodulatory effects of total extract and different polar parts from Blaps rynchopetera Fairmaire. METHODS: Phagocytic activity was evaluated by neutral red assay, and the effect of the immune function was investigated by normal and immunocompromised mice models. RESULTS: In vitro, total extract, as well as chloroform, ethyl acetate, n-butanol and water fractions could individually enhance the phagocytic ability of mouse peritoneal macrophages; in addition, chloroform and ethyl acetate fractions had an increasing tendency when combined stimulation with lipopolysaccharide (LPS). In vivo, ethyl acetate fraction (EAF) could enhance the immune organ index, increase the serum hemolysin level and peripheral blood immune cells of immunocompromised mice, while for normal mice, the effect was inconspicuous. CONCLUSIONS: Blaps rynchopetera extracts had noteworthy immunomodulatory effect, especially for individuals with immune disorders.