Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 27
Filtrar
1.
Microbiol Spectr ; 12(4): e0347723, 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38456681

RESUMEN

Canine distemper virus (CDV) poses a severe threat to both domesticated and wild animals, including multiple carnivores. With the continued expansion of its host range, there is an urgent need for the development of a safer and more effective vaccine. In this study, we developed subunit vaccines based on a bacterium-like particle (BLP) delivery platform containing BLPs-F and BLPs-H, which display the CDV F and H glycoprotein antigens, respectively, using the antigen-protein anchor fusions produced by a recombinant baculovirus insect cell expression system. The combination of BLPs-F and BLPs-H (CDV-BLPs), formulated with colloidal manganese salt [Mn jelly (MnJ)] adjuvant, triggered robust CDV-specific antibody responses and a substantial increase in the number of interferon gamma (IFN-γ)-secreting CD4+ and CD8+ T cells in mice. Dogs immunized intramuscularly with this vaccine not only produced CDV-specific IgG but also displayed elevated concentrations of IFN-γ and interleukin 6 in their serum, along with an increase of the CD3+CD4+ and CD3+CD8+ T cell subsets. Consequently, this heightened immune response provided effective protection against disease development and reduced viral shedding levels following challenge with a virulent strain. These findings suggest that this BLP-based subunit vaccine has the potential to become a novel canine distemper vaccine. IMPORTANCE: Many sensitive species require a safe and effective distemper vaccine. Non-replicating vaccines are preferred. We constructed subunit particles displaying canine distemper virus (CDV) antigens based on a bacterium-like particle (BLP) delivery platform. The CDV-BLPs formulated with theMn jelly adjuvant induced robust humoral and cell-mediated immune responses to CDV in mice and dogs, thereby providing effective protection against a virulent virus challenge. This work is an important step in developing a CDV subunit vaccine.


Asunto(s)
Virus del Moquillo Canino , Vacunas Virales , Perros , Animales , Ratones , Virus del Moquillo Canino/genética , Vacunas Virales/genética , Linfocitos T CD8-positivos , Anticuerpos Antivirales , Proteínas Recombinantes , Vacunas de Subunidad/genética
2.
J Ethnopharmacol ; 327: 118039, 2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38479545

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: The anti-tumor related diseases of Coptidis Rhizoma (Huanglian) were correlated with its traditional use of removing damp-heat, clearing internal fire, and counteracting toxicity. In the recent years, Coptidis Rhizoma and its components have drawn extensive attention toward their anti-tumor related diseases. Besides, Coptidis Rhizoma is traditionally used as an anti-inflammatory herb. Epiberberine (EPI) is a significant alkaloid isolated from Coptidis Rhizoma, and exhibits multiple pharmacological activities including anti-inflammatory. However, the effect of epiberberine on breast cancer and the inflammatory factors of metastatic breast cancer-induced osteolysis has not been demonstrated clearly. AIM OF THE STUDY: Bone metastatic breast cancer can lead to osteolysis via inflammatory factors-induced osteoclast differentiation and function. In this study, we try to analyze the effect of epiberberine on breast cancer and the inflammatory factors of metastatic breast cancer-induced osteolysis. METHODS: To evaluate whether epiberberine could suppress bone metastatic breast cancer-induced osteolytic damage, healthy female Balb/c mice were intratibially injected with murine triple-negative breast cancer 4T1 cells. Then, we examined the inhibitory effect and underlying mechanism of epiberberine on breast cancer-induced osteoclastogenesis in vitro. Xenograft assay was used to study the effect of epiberberine on breast cancer cells in vivo. Moreover, we also studied the inhibitory effects and underlying mechanisms of epiberberine on RANKL-induced osteoclast differentiation and function in vitro. RESULTS: The results show that epiberberine displayed potential therapeutic effects on breast cancer-induced osteolytic damage. Besides, our results show that epiberberine inhibited breast cancer cells-induced osteoclast differentiation and function by inhibiting secreted inflammatory cytokines such as IL-8. Importantly, we found that epiberberine directly inhibited RANKL-induced differentiation and function of osteoclast without cytotoxicity. Mechanistically, epiberberine inhibited RANKL-induced osteoclastogensis via Akt/c-Fos signaling pathway. Furthermore, epiberberine combined with docetaxel effectively protected against bone loss induced by metastatic breast cancer cells. CONCLUSIONS: Our findings suggested that epiberberine may be a promising natural compound for treating bone metastatic breast cancer-induced osteolytic damage by inhibiting IL-8 and is worthy of further exploration in preclinical and clinical trials.


Asunto(s)
Berberina/análogos & derivados , Neoplasias Óseas , Neoplasias de la Mama , Medicamentos Herbarios Chinos , Osteólisis , Humanos , Femenino , Animales , Ratones , Osteólisis/tratamiento farmacológico , Osteólisis/metabolismo , Osteólisis/patología , Neoplasias de la Mama/patología , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Medicamentos Herbarios Chinos/metabolismo , Interleucina-8/metabolismo , Osteoclastos , Osteogénesis , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/secundario , Antiinflamatorios/farmacología , Ligando RANK/metabolismo
3.
Planta Med ; 89(15): 1505-1514, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37579776

RESUMEN

A comprehensive and sensitive method combining ultra-performance liquid chromatography with tandem mass spectrometry was developed for the quantification of characteristic triterpenoids in Ganoderma mycelia. Eight ganoderic acids previously isolated from the mycelia of Ganoderma lingzhi were separated with a binary mobile phase on a reversed-phase C18 column. A triple quadrupole mass spectrometer equipped with an electrospray ionization source was used as the detector in the negative ion mode. Identification and quantitation of target ganoderic acids were accomplished using the dynamic multiple reaction monitoring mode. The developed method was validated in terms of linearity, precision, accuracy, stability, and recovery. The method was first applied to quantify the contents of eight ganoderic acids in the mycelia of G. lingzhi at different times to determine the optimum fermentation conditions. Subsequently, the distribution of triterpenoids and the contents of eight ganoderic acids in sixteen different Ganoderma species were investigated. The results indicated that UV chromatography combined with dynamic multiple reaction monitoring quantification was an effective chemotaxonomy method for Ganoderma species identification. This study also provided a helpful analytical methodology for both scientific and industrial applications in the quality control of Ganoderma triterpenoids.


Asunto(s)
Ganoderma , Triterpenos , Espectrometría de Masas en Tándem , Ganoderma/química , Triterpenos/química , Cromatografía Liquida , Esteroides , Cromatografía Líquida de Alta Presión/métodos
4.
Virol Sin ; 38(5): 787-800, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37423308

RESUMEN

The weakened protective efficacy of COVID-19 vaccines and antibodies caused by SARS-CoV-2 variants presents a global health emergency, which underscores the urgent need for universal therapeutic antibody intervention for clinical patients. Here, we screened three alpacas-derived nanobodies (Nbs) with neutralizing activity from twenty RBD-specific Nbs. The three Nbs were fused with the Fc domain of human IgG, namely aVHH-11-Fc, aVHH-13-Fc and aVHH-14-Fc, which could specifically bind RBD protein and competitively inhibit the binding of ACE2 receptor to RBD. They effectively neutralized SARS-CoV-2 pseudoviruses D614G, Alpha, Beta, Gamma, Delta, and Omicron sub-lineages BA.1, BA.2, BA.4, and BA.5 and authentic SARS-CoV-2 prototype, Delta, and Omicron BA.1, BA.2 strains. In mice-adapted COVID-19 severe model, intranasal administration of aVHH-11-Fc, aVHH-13-Fc and aVHH-14-Fc effectively protected mice from lethal challenges and reduced viral loads in both the upper and lower respiratory tracts. In the COVID-19 mild model, aVHH-13-Fc, which represents the optimal neutralizing activity among the above three Nbs, effectively protected hamsters from the challenge of SARS-CoV-2 prototype, Delta, Omicron BA.1 and BA.2 by significantly reducing viral replication and pathological alterations in the lungs. In structural modeling of aVHH-13 and RBD, aVHH-13 binds to the receptor-binding motif region of RBD and interacts with some highly conserved epitopes. Taken together, our study illustrated that alpaca-derived Nbs offered a therapeutic countermeasure against SARS-CoV-2, including those Delta and Omicron variants which have evolved into global pandemic strains.


Asunto(s)
COVID-19 , Camélidos del Nuevo Mundo , Anticuerpos de Dominio Único , Cricetinae , Humanos , Animales , Ratones , COVID-19/terapia , SARS-CoV-2/genética , Vacunas contra la COVID-19 , Anticuerpos de Dominio Único/genética , Modelos Animales de Enfermedad , Inmunoglobulina G , Anticuerpos Neutralizantes , Anticuerpos Antivirales/uso terapéutico , Glicoproteína de la Espiga del Coronavirus/genética
5.
Int J Med Mushrooms ; 25(4): 65-73, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37075085

RESUMEN

Volatile oil extracted from fermentation broth of Ganoderma lingzhi by hydrodistillation was analyzed based on gas chromatography-mass spectrometry (GC-MS). Its antitumor activity was tested on K562, SW620, A549, HepG2 cells in vitro. In addition, the antioxidant activity of the oil was determined using 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. In total, 16 constituents were identified accounting for about 99.99% of the total volatile oil in the fermentation broth of G. lingzhi. Among these components, 1-propanol (33.33%), phenylacetaldehyde (24.24%), 2-hexyl-1-decanol (12.12%) were found to be the major constituents. The antitumor results showed that the IC50 of the inhibition to the proliferation of K562, SW620, A549, HepG2 cells were 32.2, 78.9, 96.4, 99.0 µg/mL, respectively. And the oil could inhibit the proliferation of K562 cells by apoptosis induction and cell cycle arrest at S phase. Moreover, the oil exhibited radical scavenging activity (IC50 = 0.1469 mg/mL) in DPPH assay.


Asunto(s)
Ganoderma , Aceites Volátiles , Antioxidantes/farmacología , Antioxidantes/química , Aceites Volátiles/farmacología , Aceites Volátiles/química , Fermentación
6.
Front Pharmacol ; 13: 1039235, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36408232

RESUMEN

There are technical obstacles in the safety evaluation of traditional Chinese medicine (TCM) injections due to their complex chemical nature and the lack of rapid and accurate in vitro methods. Here, we established a dual in vitro mitochondrial toxicity approach combing the conventional "glucose/galactose" assay in HepG2 cells with the cytotoxic assay in mitochondrial respiration deficient cells. Using this dual in vitro approach, for the first time, we systematically assessed the mitochondrial toxicity of TCM injections. Four of the 35 TCM injections, including Xiyanping, Dengzhanhuasu, Shuanghuanglian, and Yinzhihuang, significantly reduced cellular ATP production in galactose medium in the first assay, and presented less cytotoxic in the respiration deficient cells in the second assay, indicating that they have mitochondrial toxicity. Furthermore, we identified scutellarin, rutin, phillyrin, and baicalin could be the potential mitochondrial toxic ingredients in the 4 TCM injections by combining molecular docking analysis with experimental validation. Collectively, the dual in vitro approach is worth applying to the safety evaluation of more TCM products, and mitochondrial toxic TCM injections and ingredients found in this study deserve more attention.

7.
Front Chem ; 10: 984010, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36157030

RESUMEN

Cortex Fraxini is an important traditional Chinese herbal medicine with various medical functions. Aesculin and aesculetin are the main effective components of Cortex Fraxini. The fluorescence signals of the two compounds have a high degree of overlap with each other, making quantitative analysis difficult with conventional analytical methods. In the present study, different chemometrics methods, including lasso regression (LAR), interval partial least squares (iPLS), and multidimensional partial least squares (N-PLS) methods, were employed and combined with excitation-emission matrix (EEM) fluorescence for the purpose of accurate quantification of aesculin and aesculetin in Cortex Fraxini samples. The most satisfactory results were obtained by using the N-PLS method based on the EEM spectra without scatterings, with correlation coefficient of calibration and prediction values higher than 0.9972 and 0.9962, respectively, root mean squared errors for calibration and prediction values lower than 0.0304 and 0.1165, respectively, and recovery values in the range of 83.32%-104.62%. The obtained credible models indicated that the N-PLS method combined with EEM spectra has the advantages of being green, low cost, and accurate and it is a good strategy for the determination of active compounds in complex samples. To further confirm the accuracy of the obtained results, the same samples were analyzed by the recognized ultra-performance liquid chromatography method.

8.
Viruses ; 14(8)2022 07 28.
Artículo en Inglés | MEDLINE | ID: mdl-36016285

RESUMEN

The Crimean Congo Hemorrhagic Fever Virus (CCHFV) is a tick-borne bunyavirus of the Narovirus genus, which is the causative agent of Crimean Congo Hemorrhagic Fever (CCHF). CCHF is endemic in Africa, the Middle East, Eastern Europe and Asia, with a high case-fatality rate of up to 50% in humans. Currently, there are no approved vaccines or effective therapies available for CCHF. The GEM-PA is a safe, versatile and effective carrier system, which offers a cost-efficient, high-throughput platform for recovery and purification of subunit proteins for vaccines. In the present study, based on a GEM-PA surface display system, a GEM-PA based vaccine expressing three subunit vaccine candidates (G-GP, including G-eGN, G-eGC and G-NAb) of CCHFV was developed, displaying the ectodomains of the structural glycoproteins eGN, eGC and NAb, respectively. According to the immunological assays including indirect-ELISA, a micro-neutralization test of pseudo-virus and ELISpot, 5 µg GPBLP3 combined with Montanide ISA 201VG plus Poly (I:C) adjuvant (A-G-GP-5 µg) elicited GP-specific humoral and cellular immunity in BALB/c mice after three vaccinations via subcutaneous injection (s.c.). The consistent data between IgG subtype and cytokine detection, ELISpot and cytokine detection indicated balanced Th1 and Th2 responses, of which G-eGN vaccines could elicit a stronger T-cell response post-vaccination, respectively. Moreover, all three vaccine candidates elicited high TNF-α, IL-6, and IL-10 cytokine levels in the supernatant of stimulated splenocytes in vitro. However, the neutralizing antibody (nAb) was only detected in A-G-eGC and A-G-eGC vaccination groups with the highest neutralizing titer of 128, suggesting that G-eGC could elicit a stronger humoral immune response. In conclusion, the GEM-PA surface display system could provide an efficient and convenient purification method for CCHFV subunit antigens, and the G-GP subunit vaccine candidates will be promising against CCHFV infections with excellent immunogenicity.


Asunto(s)
Virus de la Fiebre Hemorrágica de Crimea-Congo , Fiebre Hemorrágica de Crimea , Animales , Citocinas , Virus de la Fiebre Hemorrágica de Crimea-Congo/genética , Humanos , Inmunidad Humoral , Ratones , Ratones Noqueados , Aceite Mineral , Vacunas de Subunidad
9.
Front Chem ; 10: 918116, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35755259

RESUMEN

Melatonin (MT) is a hormone with antioxidant activity secreted by the pineal gland in the human brain, which is highly efficient in scavenging free radicals and plays an important role in the neuro-immuno-endocrine system. Emerging evidence showed that MT supplementation was a potential therapeutic strategy for Parkinson's disease (PD), which inhibits pathways associated with oxidative stress in PD. In this study, we reported a C7-selective olefination of melatonin under rhodium catalysis with the aid of PIII-directing groups and synthesized 10 new melatonin-C7-cinnamic acid derivatives (6a-6j). The antioxidant potential of the compounds was evaluated both by ABTS and ORAC methods. Among these newly synthesized melatonin derivatives, 6a showed significantly higher activity than MT at 10-5 M. In the transgenic Caenorhabditis elegans model of PD, 6a significantly reduces alpha-synuclein aggregation and dopaminergic neuronal damage in nematodes while reducing intracellular ROS levels and recovers behavioral dysfunction induced by dopaminergic neurodegeneration. Further study of the mechanism of action of this compound can provide new therapeutic ideas and treatment strategies for PD.

10.
J Nutr ; 152(9): 2072-2079, 2022 09 06.
Artículo en Inglés | MEDLINE | ID: mdl-35728044

RESUMEN

BACKGROUND: Supernutrition of selenium (Se) in an effort to produce Se-enriched meat may inadvertently cause lipid accumulation. Se-enriched Cardamine violifolia (SeCv) contains >80% of Se in organic forms. OBJECTIVES: This study was to determine whether feeding chickens a high dose of SeCv could produce Se-biofortified muscle without altering their lipid metabolism. METHODS: Day-old male broilers were allocated to 4 groups (6 cages/group and 6 chicks/cage) and were fed either a corn-soy base diet (BD, 0.13-0.15 mg Se/kg), the BD plus 0.5 mg Se/kg as sodium selenite (SeNa) or as SeCv, or the BD plus a low-Se Cardamine violifolia (Cv, 0.20-0.21mg Se/kg). At week 6, concentrations of Se and lipid and expression of selenoprotein and lipid metabolism-related genes were determined in the pectoral muscle and liver. RESULTS: The 4 diets showed no effects on growth performance of broilers. Compared with the other 3 diets, SeCv elevated (P < 0.05) Se concentrations in the pectoral muscle and liver by 14.4-127% and decreased (P < 0.05) total cholesterol concentrations by 12.5-46.7% and/or triglyceride concentrations by 28.8-31.1% in the pectoral muscle and/or liver, respectively. Meanwhile, SeCv enhanced (P < 0.05) muscular α-linolenic acid (80.0%) and hepatic arachidonic acid (58.3%) concentrations compared with SeNa and BD, respectively. SeCv downregulated (P < 0.05) the cholesterol and triglyceride synthesis-related proteins (sterol regulatory element binding transcription factor 2 and diacylglycerol O-acyltransferase 2) and upregulated (P < 0.05) hydrolysis and ß-oxidation of fatty acid-related proteins (lipoprotein lipase, fatty acid binding protein 1, and carnitine palmitoyltransferase 1A), as well as selenoprotein P1 and thioredoxin reductase activity in the pectoral muscle and/or liver compared with SeNa. CONCLUSIONS: Compared with SeNa, SeCv effectively raised Se and reduced lipids in the liver and muscle of broilers. The effect was mediated through the regulation of the cholesterol and triglyceride biosynthesis and utilization-related genes.


Asunto(s)
Cardamine , Selenio , Alimentación Animal , Animales , Cardamine/metabolismo , Pollos/metabolismo , Colesterol/metabolismo , Dieta/veterinaria , Suplementos Dietéticos , Lípidos/farmacología , Hígado/metabolismo , Masculino , Músculos Pectorales/metabolismo , Selenoproteínas/genética , Triglicéridos/metabolismo
11.
J Sep Sci ; 44(17): 3199-3207, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34213832

RESUMEN

A fast and simple ultra-high performance supercritical fluid chromatography method has been developed for the determination of six analytes, namely (paeonol, coumarin, cinnamic alcohol, cinnamic acid, paeoniflorin, and amygdalin) in Guizhi Fuling capsule and tablet samples. The influence of the key chromatographic parameters for the separation purposes was evaluated. The optimal column was Trefoil CEL1 column. The optimal mobile phase was a gradient mixture of carbon dioxide and methanol at flow rate of 1.0 mL/min. The back pressure of the system was set to 1.38 × 107  Pa and the temperature to 45°C. The six compounds were separated within 11 min by the proposed ultra-high performance supercritical fluid chromatography method with satisfactory resolution. Method validation confirmed that the procedure is accurate with the recovery rates from 87.04 to 104.30%, intraday precision values less than 4.81% and interday precision less than 5.22%, and linear with R2 higher than 0.9967. Therefore, this work provides a simple and novel method for the simultaneous analysis of six compounds in Guizhi Fuling capsule and tablet samples.


Asunto(s)
Medicamentos Herbarios Chinos/química , Acetofenonas/análisis , Amigdalina/análisis , Cápsulas/análisis , Cromatografía con Fluido Supercrítico , Cinamatos/análisis , Cumarinas/análisis , Glucósidos/análisis , Monoterpenos/análisis , Propanoles/análisis , Comprimidos
12.
Talanta ; 232: 122499, 2021 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-34074451

RESUMEN

In this work, ZnO nanorods (ZnO NRs) with different sizes were hydrothermally grown on the surface of Whatman filter paper for the fabrication of a microfluidic paper-based device (µPAD) for the simultaneous detection of glucose and uric acid. As dual enzymatic reaction was employed for the colorimetric detection in this µPAD, the presence of ZnO NRs promoted the enzyme immobilization thus significantly enhancing the colorimetric signal. The coffee ring effect was effectively conquered by the uniform distribution of ZnO NR as well as a specialized double-layered µPAD design. Meanwhile, two color indicators with distinct colors were used to provide complementary results to better quantify the concentration of the analytes by naked eye. As a result, two linear calibration curves were obtained for the detection of glucose (0.01-10 mmol L-1) and uric acid (0.01-5 mmol L-1), along with a LOD of 3 µmol L-1 for glucose and 4 µmol L-1 for uric acid, respectively. The practical usefulness of the proposed µPAD was further validated by the simultaneous analysis of glucose and uric acid in serum samples and urine samples.


Asunto(s)
Técnicas Analíticas Microfluídicas , Nanotubos , Óxido de Zinc , Microfluídica , Papel
13.
J Virol ; 95(18): e0060021, 2021 08 25.
Artículo en Inglés | MEDLINE | ID: mdl-34106002

RESUMEN

Coronaviruses are commonly characterized by a unique discontinuous RNA transcriptional synthesis strategy guided by transcription-regulating sequences (TRSs). However, the details of RNA synthesis in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have not been fully elucidated. Here, we present a time-scaled, gene-comparable transcriptome of SARS-CoV-2, demonstrating that ACGAAC functions as a core TRS guiding the discontinuous RNA synthesis of SARS-CoV-2 from a holistic perspective. During infection, viral transcription, rather than genome replication, dominates all viral RNA synthesis activities. The most highly expressed viral gene is the nucleocapsid gene, followed by ORF7 and ORF3 genes, while the envelope gene shows the lowest expression. Host transcription dysregulation keeps exacerbating after viral RNA synthesis reaches a maximum. The most enriched host pathways are metabolism related. Two of them (cholesterol and valine metabolism) affect viral replication in reverse. Furthermore, the activation of numerous cytokines emerges before large-scale viral RNA synthesis. IMPORTANCE SARS-CoV-2 is responsible for the current severe global health emergency that began at the end of 2019. Although the universal transcriptional strategies of coronaviruses are preliminarily understood, the details of RNA synthesis, especially the time-matched transcription level of each SARS-CoV-2 gene and the principles of subgenomic mRNA synthesis, are not clear. The coterminal subgenomic mRNAs of SARS-CoV-2 present obstacles in identifying the expression of most genes by PCR-based methods, which are exacerbated by the lack of related antibodies. Moreover, SARS-CoV-2-related metabolic imbalance and cytokine storm are receiving increasing attention from both clinical and mechanistic perspectives. Our transcriptomic research provides information on both viral RNA synthesis and host responses, in which the transcription-regulating sequences and transcription levels of viral genes are demonstrated, and the metabolic dysregulation and cytokine levels identified at the host cellular level support the development of novel medical treatment strategies.


Asunto(s)
COVID-19/genética , Células Epiteliales/metabolismo , Pulmón/metabolismo , ARN Mensajero/genética , SARS-CoV-2/aislamiento & purificación , Transcriptoma , Animales , COVID-19/metabolismo , COVID-19/virología , Células Cultivadas , Chlorocebus aethiops , Células Epiteliales/virología , Humanos , Pulmón/virología , ARN Mensajero/metabolismo , Células Vero , Replicación Viral
14.
Toxicol Res (Camb) ; 10(3): 531-541, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-34141167

RESUMEN

The use of natural substances derived from traditional Chinese medicine and natural plants as safe radiosensitizing adjuvants is a new trend for cancer radiotherapy. Ganoderma lucidum has been used as a traditional Chinese medicine with a history of more than 2000 years. Ganoderic acid T (GAT) is a typical triterpene of G. lucidum, which has strong cytotoxicity to cancer cells, but whether it has radiation sensitization effect has not been explored. In this work, we treated the HeLa cells with different concentrations of GAT before exposure to gamma-ray radiation and investigated its influence on the radiosensitivity. The cell viability, apoptosis rate, necoptosis rate, intracellular ATP level, cell cycle, the amount of H2AX and 53BP1, reactive oxygen species, and mitochondrial membrane potential were examined. Apoptotic, necroptotic, and autophagic biomarker proteins, including caspase 8, cytochrome c, caspase 3, RIPK, MLKL, P62, and LC3, were analyzed. As a result, we confirmed that with treatment of GAT, the gamma-ray radiation induced both apoptosis and necroptosis in HeLa cells, and with increase of GAT, the percentage ratio of necroptosis was increased. The involved pathways and mechanisms were also explored and discussed.

15.
Int J Med Mushrooms ; 23(3): 43-53, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33822498

RESUMEN

Ganoderma lucidum mycelia are rich in active substances such as triterpenoids and sterols. However, reports on the development of effective submerged fermentation processes are lacking and the resulting total triterpene and sterol yield is still quite low. In this study, a new G. lucidum strain G0017 mycelium isolated by screening was studied in a 3-L fermenter to investigate the effect of aeration rate in liquid submerged fermentation production of triterpenoids and sterols. By fitting the specific mycelial growth rate and the specific production rate of the triterpenoid and sterol model, an effective multistage aeration rate control process for triterpenoid and sterol fermentation production was developed. This process was validated and proven in 3-L and 50-L fermenters. The resulting yields of triterpenoids and sterols were 3.34 and 3.46 g/L, respectively, which were 69.54% and 75.63% higher than the fixed aeration rate of 1.50 volume of air per volume of liquid per minute. This optimized fermentation production process conceivably could be applied to larger-scale industrial production and perhaps also to improve liquid submerged fermentation processes with relevant edible and medicinal mushrooms.


Asunto(s)
Agaricales/química , Reishi , Esteroles/metabolismo , Triterpenos/metabolismo , Fermentación , Micelio/crecimiento & desarrollo
16.
Biochem Pharmacol ; 177: 113932, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32222456

RESUMEN

Histone post-translational modifications (PTMs) have been shown to be highly associated with inflammation response, suggesting a therapeutic significance of pharmacologically editing histone PTMs. Currently reported anti-inflammation small-molecules mainly target histone PTMs writers or erasers for methylation, phosphorylation, and acetylation. Although histone chaperones also appear to be involved in inflammation signaling cascades, whether small-molecules could target histone chaperones to show anti-inflammation effects has still been rarely discovered. In this study, natural product artone was found to show obvious inhibitory effects on microglia-mediated neuroinflammation by directly targeting ASF1a, which is a histone-remodeling chaperone. Mechanism study revealed that artone modulated histone H3 PTMs profile by down-regulating acetylation and trimethylation modification levels at sites K4, K9, K18 and K27. Artone-dependent regulations on PTMs further caused an effective inhibition on transcription factor NF-κB assembling to promoters of pro-inflammatory cytokine genes including Tnf-α, Il-6 and Rgs3, indicating a distinctive anti-neuroinflammation mechanism. Collectively, we reported artone as the first small-molecule targeting histone-remodeling chaperone ASF1a for anti-neuroinflammation. Moreover, these findings broaden our knowledge of histone chaperone as a druggable target protein for neuroinflammation inhibition, and open a new avenue to novel therapy strategy for inflammation-associated neurological disorders.


Asunto(s)
Artemisia/química , Proteínas de Ciclo Celular/metabolismo , Chaperonas de Histonas/metabolismo , Histonas/metabolismo , Lipopolisacáridos/farmacología , Microglía/citología , Microglía/efectos de los fármacos , Chaperonas Moleculares/metabolismo , Extractos Vegetales/farmacología , Sustancias Protectoras/farmacología , Acetilación/efectos de los fármacos , Animales , Proteínas de Ciclo Celular/antagonistas & inhibidores , Línea Celular , Supervivencia Celular/efectos de los fármacos , Inflamación/metabolismo , Metilación/efectos de los fármacos , Ratones , Microglía/metabolismo , Chaperonas Moleculares/antagonistas & inhibidores , Procesamiento Proteico-Postraduccional/efectos de los fármacos , Transducción de Señal/efectos de los fármacos
17.
Int J Med Mushrooms ; 22(8): 793-802, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33389873

RESUMEN

The mushroom today known as Ganoderma lingzhi has been used for centuries in the countries of Eastern Asia as a very important medicinal mushroom. It prefers growing on rotten wood of broadleaf trees and is mainly distributed in the tropics and subtropics. Its relative G. lucidum occurs naturally almost all the Earth, and it colonizes mostly oak and beech trees in Central Europe. G. lingzhi and G. lucidum are similar species. To obtain the qualitative parameters of G. lingzhi and G. lucidum, several strains (five G. lingzhi strains and five G. lucidum ones) were chosen and cultivated in both Slovakia and China, using wood chip (beech and oak) substrate and liquid fermentation method, respectively. It was found that there were more low-polarity triterpenes in G. lucidum, while G. lingzhi contained more high-polarity triterpenes. Beech substrate was more suitable for the accumulation of triterpenes in solid cultivation for both strains of G. lucidum and G. lingzhi. Strain C4 of G. lingzhi and strain K2 of G. lucidum contained higher triterpenes in either mycelium or fruiting bodies. Data in this study can help to identify these two species and bring a great benefit to the production of bioactive compounds of G. lucidum from Slovakia.


Asunto(s)
Extractos Vegetales/química , Reishi/química , Reishi/crecimiento & desarrollo , Triterpenos/química , China , Medios de Cultivo/química , Medios de Cultivo/metabolismo , Cuerpos Fructíferos de los Hongos/química , Cuerpos Fructíferos de los Hongos/crecimiento & desarrollo , Cuerpos Fructíferos de los Hongos/metabolismo , Micelio/química , Micelio/crecimiento & desarrollo , Micelio/metabolismo , Eslovaquia , Madera/química
18.
Int J Med Mushrooms ; 21(3): 207-214, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31002605

RESUMEN

To fully analyze the composition of volatile oil extracted from Tremella fuciformis, hydrodistillation (HD) and solid phase microextraction (SPME) were adopted simultaneously. In both cases, the analysis was carried out using gas chromatography-mass spectrometry and the antioxidant activity of the volatile oil was determined by the 1,1-diphenyl-2-picrylhydrazyl (DPPH) method with rutin as a positive control. Nineteen components in HD and 68 components in SPME were identified, respectively. Moreover, the oil obtained from T. fuciformis by HD indicated that aromatic compounds were a major class (93.5%), followed by the terpenes (5.7%), alkanes (0.4%), and alcohols (0.3%). Among them, butylated hydroxytoluene was the highest concentration (92.5%) of the compounds. The compounds detected by SPME were different from those of HD, and the substances with the largest content were esters (57.7%), followed by alcohols (19.0%), acids (7.0%), and aldehydes (6.3%). Only three of the same substances were detected in both of them, namely borneol, (-)-α-terpineol, and acetic acid. In the DPPH assays, strong antioxidant activity (IC50 = 0.176 mg/mL) was evident in volatile oil from T. fuciformis. Antioxidant activity was positively correlated with the concentration of volatile oil.


Asunto(s)
Agaricales/química , Antioxidantes/análisis , Aceites Volátiles/química , Compuestos Orgánicos Volátiles/análisis , Productos Biológicos/química , Cromatografía de Gases y Espectrometría de Masas , Microextracción en Fase Sólida
19.
Int J Med Mushrooms ; 17(6): 533-40, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26349511

RESUMEN

A known compound, 5-(hydroxymethyl) furan-2-carbaldehyde, and a novel compound, 3-isobutyl-1-methoxy-4-(4'-(3-methylbut-2-enyloxy)phenyl)-1H-pyrrole-2,5-dione were isolated from spent broth from submerged cultures of Taiwanofungus camphoratus. Their structures were elucidated by nuclear magnetic resonance (1H, 13C, and 2D) and mass spectra. These compounds inhibited the proliferation of K562 and HepG2 tumor cells in vitro.


Asunto(s)
Agaricales/crecimiento & desarrollo , Agaricales/metabolismo , Antineoplásicos/aislamiento & purificación , Antineoplásicos/farmacología , Medios de Cultivo/química , Antineoplásicos/química , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Hepatocitos/efectos de los fármacos , Hepatocitos/fisiología , Humanos , Espectroscopía de Resonancia Magnética , Espectrometría de Masas
20.
Artículo en Inglés | MEDLINE | ID: mdl-26221177

RESUMEN

We investigated hypoglycemic effect of ethanol (EtOH) and ethyl acetate extract acetate (AcOEt) extracts in streptozotocin- (STZ-) induced diabetic mice. Our data showed the maximum inhibitory effect on the fasting plasma glucose (FPG) level was detected in STZ-induced diabetic mice administered with 400 mg/kg AcOEt extract of P. baumii. A lower glycated albumin (GA) level and a higher insulin level were observed in 400 mg/kg AcOEt and EtOH extract groups. Moreover, 400 mg/kg AcOEt and EtOH extract exhibited a stronger effect on increasing size and cell number of islets. The insulin expression level of ß-cells and integrated optical density (IOD) value were significantly increased by the administration of 400 mg/kg AcOEt and EtOH extracts. Taken together, AcOEt and EtOH extracts of P. baumii fruiting body exhibited considerable hypoglycemic effect on STZ-induced diabetic mice.

SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA