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Somatic embryogenesis (SE) is a key regeneration pathway in various biotechnology approaches to crop improvement, especially for economically important perennial woody crops like citrus. However, maintenance of SE capability has long been a challenge and becomes a bottleneck in biotechnology-facilitated plant improvement. In the embryogenic callus (EC) of citrus, we identified 2 csi-miR171c-targeted SCARECROW-LIKE genes CsSCL2 and CsSCL3 (CsSCL2/3), which exert positive feedback regulation on csi-miR171c expression. Suppression of CsSCL2 expression by RNA interference (RNAi) enhanced SE in citrus callus. A thioredoxin superfamily protein CsClot was identified as an interactive protein of CsSCL2/3. Overexpression of CsClot disturbed reactive oxygen species (ROS) homeostasis in EC and enhanced SE. Chromatin immunoprecipitation sequencing (ChIP-Seq) and RNA-Seq identified 660 genes directly suppressed by CsSCL2 that were enriched in biological processes including development-related processes, auxin signaling pathway, and cell wall organization. CsSCL2/3 bound to the promoters of regeneration-related genes, such as WUSCHEL-RELATED HOMEOBOX 2 (CsWOX2), CsWOX13, and Lateral Organ Boundaries Domain 40 (LBD40), and repressed their expression. Overall, CsSCL2/3 modulate ROS homeostasis through the interactive protein CsClot and directly suppress the expression of regeneration-related genes, thus regulating SE in citrus. We uncovered a regulatory pathway of miR171c-targeted CsSCL2/3 in SE, which shed light on the mechanism of SE and regeneration capability maintenance in citrus.
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Citrus , Citrus/genética , Citrus/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Biotecnología , RNA-Seq , Regeneración , Técnicas de Embriogénesis Somática de Plantas , Regulación de la Expresión Génica de las PlantasRESUMEN
Dendrobium huoshanense flowers have been widely used for liver protection in China. This work was aimed to discover the natural products with activity of mitigating alcoholic hepatocyte injury from Dendrobium huoshanense flowers via bioactivity-guided isolation, and to clarify the underlying mechanisms of these natural products. As a result, three flavonoids, 3'-O-methylquercetin-3-O-ß-D-galactopyranoside (1), 3'-O-methylquercetin-3-O-ß-D-glucopyranoside (2) and quercetin-3-O-ß-D-glucopyranoside (3), were firstly isolated from D. huoshanense flowers. Results exhibited that flavonoids 1-3 could enhance the cell viability, decrease the expression of ALT and AST, inhibit the cell apoptosis, alleviate the oxidative stress, and mitigate the inflammatory response of alcohol-induced L02 cells. Mechanism study exhibited that flavonoids 1-3 could increase the expression of Nrf2 as well as its downstream antioxidation genes of alcohol-induced L02 cells, while ML-385 (Nrf2 inhibitor) could abolish the inhibitory effects of 1-3 on alcohol-induced hepatocyte injury. Flavonoids 1-3 could also reduce the phosphorylation levels of IκBα and NF-κB p65 of alcohol-induced L02 cells, while SC75741 (NF-κB inhibitor) could not enhance the inhibitory effects of 1-3 on alcohol-induced L02 cells injury. The data above indicated that flavonoids 1-3 could inhibit alcohol-induced hepatocyte injury, which might be attributed to alleviating oxidative stress and mitigating inflammatory response by activating Nrf2 and inhibiting NF-κB pathways.
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Productos Biológicos , Dendrobium , Productos Biológicos/farmacología , Etanol/farmacología , Flavonoides/farmacología , Flores/metabolismo , Hepatocitos/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , FN-kappa B/metabolismo , Estrés OxidativoRESUMEN
OBJECTIVE: Candida glabrata (C. glabrata) causes infections associated with severe sepsis and high mortality. This study describes the effects of micafungin (MCF), itraconazole (ICZ), and amphotericin B (AmB) on the function of macrophages during C. glabrata infection. METHODS: RAW264.1 macrophages were treated with MCF, ICZ, or AmB and then challenged with C. glabrata. Cytokines from infected macrophage supernatants and the levels of superoxide dismutase (SOD) in macrophages were measured at different time points after phagocytosis. RESULTS: The activity of SOD was significantly increased in RAW264.1 cells that phagocytized C. glabrata and reached a peak level at 6 hours (P < 0.05). ICZ and AmB did not affect the SOD activity in cells that phagocytized C. glabrata versus that in untreated macrophage. C. glabrata stimulated macrophages to secrete cytokines. Neither ICZ nor AmB affected the secretion of interleukin-6 (IL-6), interleukin-8 (IL-8), or tumor necrosis factor-α (TNF-α) by C. glabrata-infected macrophages. However, MCF downregulated the secretion of TNF-α by infected macrophages and reduced the SOD activity of C. glabrata compared with those in untreated controls. CONCLUSION: Echinocandins may increase their antifungal efficacy by altering the innate immune response of macrophages and attenuating antioxidants of this organism.
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KEY MESSAGE: The physical locations of citrus centromere are revealed by combining genetic and immunological assays for the first time and nine citrus centromere-specific markers for cytogenetics are mined. Centromere localization is challenging, because highly redundant repetitive sequences in centromeric regions make sequence assembly difficult. Although several citrus genomes have been released, the centromeric regions and their characteristics remain to be elucidated. Here, we mapped citrus centromeres through half-tetrad analysis (HTA) that included the genotyping of 54 tetraploid hybrids derived from 2n megagametophytes of Nadorcott tangor with 212 single nucleotide polymorphism (SNP) markers. The sizes of centromeric regions, which estimated based on the heterozygosity restitution rate pattern along the chromosomes, ranged from 1.12 to 18.19 Mb. We also profiled the binding sequences with the centromere-specific histone variant CenH3 by chromatin immunoprecipitation sequencing (ChIP-seq). Based on the positions of the top ten CenH3-enriched contigs, the sizes of centromeric regions were estimated to range from 0.01 to 7.60 Mb and were either adjacent to or included in the centromeric regions identified by HTA. We used DNA probes from two repeats selected from the centromeric regions and seven CenH3-binding centromeric repeats to verify centromeric locations by fluorescence in situ hybridization (FISH). Centromere localization in citrus will contribute to the mining of centromeric/pericentromeric markers, thus to facilitate the rapid identification of mechanisms underlying 2n gamete formation and serve the polyploidy breeding.
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Centrómero/genética , Citrus/genética , Citogenética/métodos , Especificidad de Anticuerpos , Secuenciación de Inmunoprecipitación de Cromatina , Genes de Plantas/inmunología , Técnicas de Genotipaje/métodos , Hibridación Fluorescente in Situ , Polimorfismo de Nucleótido Simple , TetraploidíaRESUMEN
Three bibenzyls 1-3 and six other compounds 4-9 were firstly isolated from Dendrobium huoshanense stems. They were identified as 3',4-dihydroxy-3,5'-dimethoxybibenzyl(1), batatasin â ¢(2), 3,4'-dihydroxy-5-methoxy bibenzyl(3), dihydroconiferyl dihydro-p-coumarate(4), syringaresinol(5), 3-(4-hydroxyphenyl)-propionic acid ethyl ester(6),(3-ethylphenyl)-1,2-ethanediol(7),(S)-5-hydroxy-3,4-dimethyl-5-pentylfuran-2(5H)-one(8) and loliolide(9). Anti-inflammation assay showed that bibenzyls 1-3 could significantly inhibit the production of nitric oxide(NO) and the expression of tumor necrosis factor α(TNF-α) and interleukin 1ß(IL-1ß) mRNA in LPS-induced RAW264.7 macrophages. Mechanism study exhibited that the phosphorylation of nuclear factor kappa B(NF-κB) p65, inhibitor of κB(IκB), extracellular regulatedprotein kinase(ERK), c-Jun N-terminalkinase(JNK), p38 and Akt of LPS-induced RAW264.7 macrophages could be remarkably reduced by 1. These results suggested that the inflammatory response of LPS-induced RAW264.7 macrophages could be significantly inhibited by 1-3. Additionally, the anti-inflammatory effect of 1 might be contributed to its ability on the regulation of NF-κB, MAPKs and Akt signaling pathways.
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Dendrobium , Antiinflamatorios/uso terapéutico , Humanos , Inflamación/tratamiento farmacológico , Lipopolisacáridos , Macrófagos , FN-kappa B , Óxido Nítrico , Óxido Nítrico Sintasa de Tipo IIRESUMEN
Chronic renal failure (CRF) is a major public health problem worldwide. In this work, we investigated the effects of a purified Laminaria japonica polysaccharide (LJP61A) on renal function using an adenine-induced CRF mice model. Results exhibited that adenine treatment caused serious renal pathological damages and elevation of serum creatinine and blood urea nitrogen of mice. However, these changes could be significantly reversed by the administration of LJP61A in a dose-dependent manner. Additionally, LJP61A could dramatically reduce weight loss, improve the urine biochemical index, and regulate the electrolyte disturbance of CRF mice. These results suggest that the renal function of adenine-induced CRF mice can be improved by LJP61A, which might be developed into a potential therapeutic agent for CRF patients.
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Adenina/efectos adversos , Fallo Renal Crónico/etiología , Fallo Renal Crónico/prevención & control , Laminaria/química , Polisacáridos/farmacología , Sustancias Protectoras/farmacología , Animales , Peso Corporal , Modelos Animales de Enfermedad , Fallo Renal Crónico/tratamiento farmacológico , Fallo Renal Crónico/patología , Masculino , Ratones , Polisacáridos/química , Sustancias Protectoras/químicaRESUMEN
Involucratustones A-C (1-3), three cadinane dimers containing multiple contiguous quaternary carbons, were isolated from the rhizomes of Stahlianthus involucratus. Their structures were determined by a combination of NMR spectroscopy, chemical conversion, and X-ray diffraction analysis. Compounds 1 and 2 are rearranged homodimers of cadinane sesquiterpene fused with a unique fully substituted 1-oxaspiro[4.4]nonane core observed for the first time in natural products, and 3 is a novel 3',4'-seco-cadinane-dimer. Compounds 1 and 2 exhibited potent cytotoxic activities, and 3 showed notable anti-inflammatory effect.
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Productos Biológicos/química , Sesquiterpenos/química , Compuestos de Espiro/química , Productos Biológicos/aislamiento & purificación , Espectroscopía de Resonancia Magnética , Estructura Molecular , Sesquiterpenos/aislamiento & purificación , Difracción de Rayos XRESUMEN
A new sesquiterpenoid, 1, and three new diterpenoids, 3-5, along with five known compounds, 2 and 6-9, were isolated from rhizomes of Alpinia japonica. The structures of the new compounds were determined as (1R,4R,6S,7S,9S)-4α-hydroxy-1,9-peroxybisabola-2,10-diene (1), methyl (12E)-16-oxolabda-8(17),12-dien-15-oate (3), (12R)-15-ethoxy-12-hydroxylabda-8(17),13(14)-dien-16,15-olide (4), and methyl (11E)-14,15,16-trinorlabda-8(17),11-dien-13-oate (5) by means of spectroscopic data. The absolute configurations at C(4) in 1 and C(12) in 4 were deduced from the circular dichroism (CD) data of the in situ-formed [Rh2 (CF3 COO)4 ] complexes. Inhibitory effects of the isolates on NO production in lipopolysaccharide-induced RAW264.7 macrophages were evaluated, and 2-4, 6, and 7 were found to exhibit inhibitory activities with IC50 values between 14.6 and 34.3â µM.
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Alpinia/química , Antiinflamatorios/farmacología , Macrófagos/efectos de los fármacos , Óxido Nítrico/antagonistas & inhibidores , Rizoma/química , Terpenos/farmacología , Animales , Antiinflamatorios/química , Antiinflamatorios/aislamiento & purificación , Línea Celular , Lipopolisacáridos/inmunología , Macrófagos/inmunología , Ratones , Óxido Nítrico/inmunología , Terpenos/química , Terpenos/aislamiento & purificaciónRESUMEN
Laggera pterodonta is commonly used for treating influenza in Southwest China, especially in Yunnnan province. The main clinical effects of L. pterodonta include anti-influenza, anti-microbial, anti-inflammatory. To investigate the anti-influenza A (H1N1) virus effect of L. pterodonta, neutralization inhibition and proliferation inhibition tests were performed. MDCK culture method was used to observe the cytopathic effect (CPE) of extracts from L. pterodonta in inhibiting influenza A (H1N1) virus and haemagglutination titre of H1N1 virus in vitro. The culture medium were collected at 24 h, 48 h, 72 h, 96 h, and detected by Real time RT-PCR, in order to compare the effect of different extracts from L. pterodonta on in vitro proliferation of H1N1, virus. The result of neutralization inhibition test showed that hemagglutination titer of ethyl acetate extract were 8 times lower at 72 h; in proliferation inhibition test, hemagglutination titer of ethyl acetate extracts reduced by 2 and 4 times. According to the results of Real time RT-PCR test, the H1N1 inhibition ratio of ethyl acetate extract was 72.5%, while the proliferation inhibition ratio of ethyl acetate extract was 25.3%; as for petroleum ether extracts, the H1N1 inhibition ratio was 60.2%, while the proliferation inhibition ratio was 81.4%. In conclusion, both ethyl acetate extract and petroleum ether extract of L. pterodonta have significant neutralization and direct proliferation inhibition effects on influenza A virus.
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Asteraceae/química , Medicamentos Herbarios Chinos/farmacología , Subtipo H1N1 del Virus de la Influenza A/efectos de los fármacos , Gripe Humana/tratamiento farmacológico , China/etnología , Medicamentos Herbarios Chinos/aislamiento & purificación , Humanos , Subtipo H1N1 del Virus de la Influenza A/fisiología , Gripe Humana/virología , Medicina Tradicional ChinaRESUMEN
To address the issue of the lack of red light in traditional Ce3+: YAG-encapsulated blue LED white light systems, we utilized spark plasma sintering (SPS) to prepare spinel-based Cr3+-doped red phosphor ceramics. Through phase and spectral analysis, the SPS-sintered ZnAl2O4: 0.5%Cr3+ phosphor ceramic exhibits good density, and Cr3+ is incorporated into [AlO6] octahedra as a red emitting center. We analyzed the reasons behind the narrow-band emission and millisecond-level lifetime of ZAO: 0.5%Cr3+, attributing it to the four-quadrupole interaction mechanism as determined through concentration quenching modeling. Additionally, we evaluated the thermal conductivity and thermal quenching performance of the ceramic. The weak electron-phonon coupling (EPC) effects and emission from antisite defects at 699 nm provide positive assistance in thermal quenching. At a high temperature of 150 °C, the thermal conductivity reaches up to 14 W·m-1·K-1, and the 687 nm PL intensity is maintained at around 70% of room temperature. Furthermore, the internal quantum efficiency (IQE) of ZAO: 0.5%Cr3+ phosphor ceramic can reach 78%. When encapsulated with Ce3+: YAG for a 450 nm blue LED, it compensates for the lack of red light, adjusts the color temperature, and improves the color rendering index (R9). This provides valuable insights for the study of white light emitting diodes (WLEDs).
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ETHNOPHARMACOLOGICAL RELEVANCE: Ganoderma lucidum, a renowned tonic traditional Chinese medicine, is widely recognized for the exceptional activity in soothing nerves and nourishing the brain. It has been extensively employed to alleviate various neurological disorders, notably Parkinson's disease (PD). AIM OF THE STUDY: To appraise the antiparkinsonian effect of GAA, the main bioactive constituent of G. lucidum, and clarify the molecular mechanism through the perspective of ferritinophagy-mediated dopaminergic neuron ferroptosis. MATERIALS AND METHODS: PD mouse and cell models were established using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 1-methyl-4-phenylpyridinium (MPP+), respectively. Cell viability, behavioral tests and immunofluorescence analysis were performed to evaluate the neurotoxicity, motor dysfunction and dopaminergic loss, respectively. Biochemical assay kits were used to determine the levels of iron, lipid reactive oxygen species (ROS), malondialdehyde (MDA), total ROS and glutathione (GSH). Western blot and immunofluorescence were applied to detect the expressions of nuclear receptor co-activator 4 (NCOA4), ferritin heavy chain 1 (FTH1), p62 and LC3B. Additionally, NCOA4-overexpressing plasmid vector was constructed to verify the inhibitory effect of GAA on the neurotoxicity and ferroptosis-related parameters in PD models. RESULTS: GAA significantly mitigated MPP+/MPTP-induced neurotoxicity, motor dysfunction and dopaminergic neuron loss (pï¼0.01 or pï¼0.05). In contrast to MPP+/MPTP treatment, GAA treatment decreased the levels of iron, MDA, lipid and total ROS, while increasing the GSH level. GAA also reduced the levels of NCOA4 and LC3B, and enhanced the expressions of FTH1 and p62 in PD models (pï¼0.01 or pï¼0.05). However, the protective effect of GAA against the neurotoxicity, NCOA4-mediated ferritinophagy and ferroptosis in PD model was abolished by the overexpression of NCOA4 (pï¼0.01). CONCLUSION: GAA exerted a protective effect on PD, and this effect was achieved by suppressing dopaminergic neuron ferroptosis through the inhibition of NCOA4-mediated ferritinophagy.
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Neuronas Dopaminérgicas , Ferritinas , Ferroptosis , Ratones Endogámicos C57BL , Coactivadores de Receptor Nuclear , Animales , Ferroptosis/efectos de los fármacos , Neuronas Dopaminérgicas/efectos de los fármacos , Neuronas Dopaminérgicas/metabolismo , Neuronas Dopaminérgicas/patología , Coactivadores de Receptor Nuclear/metabolismo , Ratones , Masculino , Ferritinas/metabolismo , Fármacos Neuroprotectores/farmacología , Autofagia/efectos de los fármacos , Antiparkinsonianos/farmacología , Trastornos Parkinsonianos/tratamiento farmacológico , Trastornos Parkinsonianos/metabolismo , Trastornos Parkinsonianos/inducido químicamente , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/metabolismo , Modelos Animales de EnfermedadRESUMEN
Glucagon-like peptide-1 (GLP-1) as a multifunctional hormone is secreted mainly from enteroendocrine L-cells, and enhancing its endogenous secretion has potential benefits of regulating glucose homeostasis and controlling body weight gain. In the present study, a novel polysaccharide (h-DHP) with high ability to enhance plasma GLP-1 level in mice was isolated from Dendrobium huoshanense protocorm-like bodies under the guidance of activity evaluation. Structural identification showed that h-DHP was an acidic polysaccharide with the molecular weight of 1.38â¯×â¯105â¯Da, and was composed of galactose, glucose, arabinose and glucuronic acid at a molar ratio of 15.7: 11.2: 4.5: 1.0 with a backbone consisting of â5)-α-L-Araf-(1â, â3)-α-D-Galp-(1â, â6)-α-D-Galp-(1â, â3,6)-α-D-Galp-(1â, â6)-ß-D-Glcp-(1â and â4,6)-ß-D-Glcp-(1â along with branches consisting of α-L-Araf-(1â, α-D-Galp-(1â, α-D-GlcAp-(1â, ß-D-Glcp-(1â and â4)-ß-D-Glcp-(1â. Animal experiments with different administration routes demonstrated that h-DHP-enhanced plasma GLP-1 level was attributed to h-DHP-promoted GLP-1 secretion in the enteroendocrine L-cells, which was supported by h-DHP-enhanced extracellular GLP-1 level in STC-1 cells. Inhibition of adenylate cyclase and phospholipase C indicated that cAMP and cAMP-triggered intracellular Ca2+ increase participated in h-DHP-promoted GLP-1 secretion. These results suggested that h-DHP has the potential of enhancing endogenous GLP-1 level through h-DHP-promoted and cAMP-mediated GLP-1 secretion from enteroendocrine cells.
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This study aims to investigate the ameliorative effect of Codonopsis lanceolata polysaccharide (PCL) on mice with hypogalatia induced by a high-fat diet (HFD) and the potential underlying mechanism. We found that oral administration of PCL demonstrated significant benefits in countering the negative effects of HFD, including weight gain, hepatic steatosis, mesenteric adipocyte hypertrophy, and abnormal glucose/lipid metabolism. In addition, PCL improved mammary gland development and enhanced lactogenesis performance. Histologically, PCL ameliorated the retardation of ductal growth, reduced mammary fat pad thickness, improved the incomplete linear encapsulation of luminal epithelium and myoepithelium, and increased the proliferation of mammary epithelial cells. Flow cytometry analysis showed that PCL mitigated the detrimental effects of HFD on mammary gland development by promoting the proliferation and differentiation of mammary epithelial cells. Mechanistic studies revealed that PCL upregulated the levels of prolactin (PRL) and its receptor (PRLR) in the mammary gland, activated JAK2/STAT5 signaling pathway, and increased the expression of p63, ERBB4, and NRG1. Overall, PCL can ameliorate HFD-induced hypogalactia by activating PRLR-mediated JAK2/STAT5 signaling. Our findings offer a methodological and theoretical foundation for investigating the functional constituents of traditional Chinese medicine in the treatment of hypogalactia.
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Codonopsis , Trastornos de la Lactancia , Humanos , Femenino , Ratones , Animales , Prolactina/metabolismo , Prolactina/farmacología , Receptores de Prolactina/metabolismo , Codonopsis/metabolismo , Factor de Transcripción STAT5/metabolismo , Dieta Alta en Grasa/efectos adversos , Transducción de Señal , Periodo Posparto , Polisacáridos/farmacologíaRESUMEN
Renal tubular ectopic lipid deposition (ELD) plays a significant role in the development of chronic kidney disease, posing a great threat to human health. The present work aimed to explore the intervention effect and potential molecular mechanism of a purified tea polysaccharide (TPS3A) on renal tubular ELD. The results demonstrated that TPS3A effectively improved kidney function and slowed the progression of tubulointerstitial fibrosis in high-fat-diet (HFD)-exposed ApoE-/- mice. Additionally, TPS3A notably suppressed lipogenesis and enhanced lipolysis, as shown by the downregulation of lipogenesis markers (SREBP-1 and FAS) and the upregulation of lipolysis markers (HSL and ATGL), thereby reducing renal tubular ELD in HFD-fed ApoE-/- mice and palmitic-acid-stimulated HK-2 cells. The AMPK-SIRT1-FoxO1 axis is a core signal pathway in regulating lipid deposition. Consistently, TPS3A significantly increased the levels of phosphorylated-AMPK, SIRT1, and deacetylation of Ac-FoxO1. However, these effects of TPS3A on lipogenesis and lipolysis were abolished by AMPK siRNA, SIRT1 siRNA, and FoxO1 inhibitor, resulting in exacerbated lipid deposition. Taken together, TPS3A shows promise in ameliorating renal tubular ELD by inhibiting lipogenesis and promoting lipolysis through the AMPK-SIRT1-FoxO1 signaling pathway.
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Dieta Alta en Grasa , Lipogénesis , Lipólisis , Ratones Endogámicos C57BL , Polisacáridos , Animales , Lipogénesis/efectos de los fármacos , Ratones , Lipólisis/efectos de los fármacos , Masculino , Dieta Alta en Grasa/efectos adversos , Humanos , Polisacáridos/farmacología , Polisacáridos/administración & dosificación , Sirtuina 1/metabolismo , Sirtuina 1/genética , Proteína Forkhead Box O1/metabolismo , Proteína Forkhead Box O1/genética , Túbulos Renales/metabolismo , Túbulos Renales/efectos de los fármacos , Camellia sinensis/química , Proteínas Quinasas Activadas por AMP/metabolismo , Proteínas Quinasas Activadas por AMP/genética , Extractos Vegetales/farmacología , Extractos Vegetales/administración & dosificación , Té/química , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/metabolismo , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/genéticaRESUMEN
An amyloid-ß (Aß) fibril is a vital pathogenic factor of Alzheimer's disease (AD). Aß fibril disintegrators possess great potential to be developed into novel anti-AD agents. Here, a ligand fishing method was employed to rapidly discover Aß42 fibril disintegrators from Ganoderma lucidum using Aß42 fibril-immobilized magnetic beads, which led to the isolation of six Aß42 fibril disintegrators including ganodermanontriol, ganoderic acid DM, ganoderiol F, ganoderol B, ganodermenonol, and ergosterol. Neuroprotective evaluation in vitro exhibited that these Aß42 fibril disintegrators could significantly mitigate Aß42-induced neurotoxicity. Among these six disintegrators, ergosterol and ganoderic acid DM with stronger protecting activity were further selected to evaluate their neuroprotective effect on AD in vivo. Results showed that ergosterol and ganoderic acid DM could significantly alleviate Aß42-induced cognitive dysfunction and hippocampus neuron loss in vivo. Moreover, ergosterol and ganoderic acid DM could significantly inhibit Aß42-induced neuron apoptosis and Nrf2-mediated neuron oxidative stress in vitro and in vivo.
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Enfermedad de Alzheimer , Fármacos Neuroprotectores , Reishi , Triterpenos , Enfermedad de Alzheimer/tratamiento farmacológico , Fármacos Neuroprotectores/farmacología , Ligandos , Péptidos beta-Amiloides , Amiloide , Ergosterol , Fragmentos de Péptidos/uso terapéuticoRESUMEN
A new homogeneous polysaccharide (TPS3A) was isolated and purified from Tianzhu Xianyue fried green tea by DEAE-52 cellulose and Sephacryl S-500 column chromatography. Structural characterization indicated that TPS3A mainly consisted of arabinose, galactose, galacturonic acid and rhamnose in a molar ratio of 5.84: 4.15: 2.06: 1, with an average molecular weight of 1.596 × 104 kDa. The structure of TPS3A was characterized as a repeating unit consisting of 1,3-Galp, 1,4-Galp, 1,3,6-Galp, 1,3-Araf, 1,5-Araf, 1,2,4-Rhap and 1-GalpA, with two branches on the C6 of 1,3,6-Galp and C2 of 1,2,4-Rhap, respectively. To investigate the preventive effects of TPS3A on atherosclerosis, TPS3A was administered orally to ApoE-deficient (ApoE-/-) mice. Results revealed that TPS3A intervention could effectively delay the atherosclerotic plaque progression, modulate dyslipidemia, and reduce the transformation of vascular smooth muscle cells (VSMCs) from contractile phenotype to synthetic phenotype by activating the expression of contractile marker alpha-smooth muscle actin (α-SMA) and inhibiting the expression of synthetic marker osteopontin (OPN) in high-fat diet-induced ApoE-/- mice. Our findings suggested that TPS3A markedly alleviated atherosclerosis by regulating dyslipidemia and phenotypic transition of VSMCs, and might be used as a novel functional ingredient to promote cardiovascular health.
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Aterosclerosis , Dislipidemias , Animales , Ratones , Té , Polisacáridos/farmacología , Polisacáridos/uso terapéutico , Polisacáridos/análisis , Aterosclerosis/tratamiento farmacológico , Apolipoproteínas ERESUMEN
Lu3Al5O12:Ce3+ phosphor ceramics were fabricated by vacuum sintering. On this basis, a bi-layer composite phosphor was prepared by low-temperature sintering to cover the phosphor ceramics with a layer of SrAlSiN3:Eu2+-phosphor-in-glass (PiG). The optical, thermal, and colorimetric properties of LuAG:Ce3+ phosphor ceramics, SrAlSiN3:Eu2+ phosphors and SrAlSiN3:Eu2+-PiG were studied individually. Combining the bi-layer composite phosphors with the blue LED chip, it is found that the spectrum can be adjusted by varying the doping concentration of SrAlSiN3:Eu2+-PiG and the thickness of Lu3Al5O12:Ce3+ phosphor ceramics. The maximal color rendering index value of the white LED is 86, and the R9 is 61. Under the excitation of a laser diode, the maximum phosphor conversion efficacy of the bi-layer composite phosphors is 120 lm/W, the Ra is 83, and the correlated color temperature is 4534 K. These results show that the bi-layer composite phosphor ceramic is a candidate material to achieve high color rendering index for high brightness lighting.
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Ulcerative colitis (UC) is a chronic inflammatory bowel disease with unknown etiology and difficult treatment. In this study, the intervention effect of Dendrobium fimbriatum Hook polysaccharide (cDFPW1) on UC was verified by constructing a dextran sulfate sodium (DSS)-induced colitis mouse model, and the protective effect of cDFPW1 on intestinal mucosal integrity in UC was explored by the co-culture system consisting of intestinal organoids and lamina propria lymphocytes (LPLs) combined with the experiment of microbial depletion mice. Results showed that cDFPW1 significantly alleviated UC symptoms in mice and promoted the proliferation of intestinal epithelial cells. Importantly, cDFPW1 could directly improve DSS-induced morphological damage of intestinal organoids and increase the number of epithelial cells, which was validated in mice. During repair, an increase in the number of Lgr5+ cells in intestinal organoids and mouse intestines was promoted by cDFPW1. Meanwhile, cDFPW1 promoted intestinal stem cells (ISCs)-mediated intestinal epithelial regeneration by significantly upregulating IL-22 expression. We further confirmed that the secretion of IL-22 was mediated by LPLs. Together, these findings suggest that cDFPW1 promotes ISCs regeneration by LPLs-mediated up-regulation of IL-22 to protect the intestinal mucosal integrity, thereby playing an important role in improving UC.
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Colitis Ulcerosa , Colitis , Dendrobium , Animales , Ratones , Colitis/inducido químicamente , Colitis Ulcerosa/metabolismo , Sulfato de Dextran/toxicidad , Modelos Animales de Enfermedad , Interleucinas/metabolismo , Mucosa Intestinal/metabolismo , Ratones Endogámicos C57BL , Células Madre , Interleucina-22RESUMEN
This study aimed to explore whether Dendrobium huoshanense stem polysaccharide (cDHPS) ameliorates alcohol-induced gastric ulcer (GU) through the strengthening effect of the gastric mucosal barrier in rats and its potential mechanism. In normal rats, the pretreatment of cDHPS effectively strengthened gastric mucosal barrier by increasing mucus secretion and tight junction protein expression. In GU rats, cDHPS supplementation effectively alleviated alcohol-induced gastric mucosal injury and nuclear factor κB (NF-κB)-driven inflammation by strengthening gastric mucosal barrier. Moreover, cDHPS significantly activated nuclear factor E2-related factor 2 (Nrf2) signaling and promoted antioxidant enzymes activities in both normal and GU rats. These results suggested that the pretreatment of cDHPS could strengthen gastric mucosal barrier to inhibit oxidative stress and NF-κB-driven inflammation induced gastric mucosal injury, which was likely related to the activation of Nrf2 signaling.
Asunto(s)
Dendrobium , Úlcera Gástrica , Ratas , Animales , FN-kappa B/metabolismo , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/tratamiento farmacológico , Úlcera Gástrica/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Antioxidantes/farmacología , Inflamación , Polisacáridos/efectos adversosRESUMEN
In the present work, we explored the interventional effect and potential mechanism of a purified Laminaria japonica polysaccharide (LJP61A) on podocyte epithelial-mesenchymal transition (EMT) in TGF-ß1-induced podocytes and adriamycin-treated mice. Results showed that compared to the model groups, LJP61A significantly up-regulated the levels of epithelial markers (Nephrin, WT-1, podocin) and down-regulated the levels of mesenchymal markers (α-SMA, FN1) in vitro and in vivo, thus preventing EMT-like morphological changes of podocytes, proteinuria and kidney injury. Smad3 and p38MAPK are two central pathways mediating podocyte EMT activated by TGF-ß1. We found that LJP61A suppressed TGF-ß1-induced activation of Smad3, Smad4 and p38MAPK in vitro and in vivo. Moreover, the inhibitory actions of LJP61A on podocyte EMT were synergistically strengthened by Smad3 inhibitor SIS3 and p38MAPK inhibitor SB203580. Taken together, these findings revealed that LJP61A could prevent podocyte EMT, which might be related to the inhibition of TGF-ß1-mediated Smad3 and p38MAPK pathways.