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1.
Dev Comp Immunol ; 147: 104896, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37473826

RESUMEN

Yeast is a health-promoting and bio-therapeutic probiotic that is commonly used in aquaculture. Rhodotorula paludigena CM33 can accumulate amounts of intracellular carotenoids and lipid, which are regarded as nutritionally beneficial compounds in various aspects. The aim of this study was to evaluate the impact of different levels of R. paludigena CM33 (RD) incorporated in a dietary composition at 0% (control), 1% (1% RD), 2% (2% RD), and 5% (5% RD) on the growth of shrimp (Litopenaeus vannamei), their immune-related gene expression, intestinal health, resistance to Vibrio parahaemolyticus (VPAHPND) infection, and meat composition. The results showed significant improvements in the specific growth rate, weight gain, and survival of shrimp fed with 1% RD, 2% RD, and 5% RD, which were higher than the control group after 4 weeks of administration. The administration of 5% RD group resulted in a decrease in cumulative mortality upon VPAHPND challenge when compared to the control group. Furthermore, the expression levels of immune-responsive genes, including proPO system (prophenoloxidase-2: PO2), antioxidant enzyme (superoxide dismutase: SOD, glutathione peroxidase: GPX, and catalase: CAT), JAK/STAT pathway (signal transducer and activator of transcription: STAT, gamma interferon inducible lysosomal thiol reductase: GILT), IMD pathway (inhibitor of nuclear factor kappa-B kinase subunit beta and epsilon: IKKb and IKKe), and Toll pathway (Lysozyme) genes, were up-regulated in the 5% RD group. In the context of microbiota, microbiome analysis revealed that the main phyla in shrimp intestines were Proteobacteria, Firmicutes, Bacteroidota, Campilobacterota, Actinobacteriota, and Verrucomicrobiota. At the genus level, Vibrio was found to be reduced in the 5% RD group, whereas the abundance of potentially beneficial bacteria Bifidobacterium was increased. The 5% RD group showed a significant increase in the levels of crude protein and crude lipid, both of which are essential nutritious components. Our results show the capability of R. paludigena CM33 as a probiotic supplement in shrimp feed in improving growth, antimicrobial responses against VPAHPND, and meat quality by increasing protein and lipid content in shrimp.


Asunto(s)
Penaeidae , Vibrio parahaemolyticus , Animales , Resistencia a la Enfermedad/genética , Inmunidad Innata , Quinasas Janus/genética , Transducción de Señal , Factores de Transcripción STAT/genética , Dieta , Suplementos Dietéticos , Alimentos Marinos , Intestinos , Expresión Génica , Lípidos , Penaeidae/genética , Vibrio parahaemolyticus/fisiología
2.
Zool Res ; 43(3): 301-318, 2022 May 18.
Artículo en Inglés | MEDLINE | ID: mdl-35312240

RESUMEN

Hyperproteinemia is a metabolic disorder associated with increased plasma protein concentration (PPC) and is often clinically complicated by malignant diseases or severe infections. At present, however, research on the molecular mechanism underlying high PPC (HPPC) is scant. Here, an animal model of primary hyperproteinemia was constructed in an invertebrate ( Bombyx mori) to investigate the effects of HPPC on circulating blood cells. Results showed that HPPC affected blood cell homeostasis, leading to increased reactive oxygen species levels, and induced programmed cell death dependent on the endoplasmic reticulum-calcium ion signaling pathway. HPPC induced the proliferation of blood cells, mainly granulocytes, by activating the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway. Supplementation with the endocrine hormone active substance 20E significantly reduced the impact of HPPC on blood cell homeostasis. Thus, we identified a novel signaling pathway by which HPPC affects blood cell homeostasis, which differs from hyperglycemia, hyperlipidemia, and hypercholesterolemia. In addition, we showed that down-regulation of gene expression of the hematopoietic factor Gcm could be used as a potential early detection indicator for hyperproteinemia.


Asunto(s)
Quinasas Janus , Factores de Transcripción STAT , Animales , Células Sanguíneas/metabolismo , Modelos Animales de Enfermedad , Homeostasis , Quinasas Janus/genética , Quinasas Janus/metabolismo , Factores de Transcripción STAT/genética , Factores de Transcripción STAT/metabolismo
3.
J Cell Mol Med ; 26(7): 2049-2062, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35229974

RESUMEN

Through a comprehensive review and in silico analysis of reported data on STAT-linked diseases, we analysed the communication pathways and interactome of the seven STATs in major cancer categories and proposed rational targeting approaches for therapeutic intervention to disrupt critical pathways and addictions to hyperactive JAK/STAT in neoplastic states. Although all STATs follow a similar molecular activation pathway, STAT1, STAT2, STAT4 and STAT6 exert specific biological profiles associated with a more restricted pattern of activation by cytokines. STAT3 and STAT5A as well as STAT5B have pleiotropic roles in the body and can act as critical oncogenes that promote many processes involved in cancer development. STAT1, STAT3 and STAT5 also possess tumour suppressive action in certain mutational and cancer type context. Here, we demonstrated member-specific STAT activity in major cancer types. Through systems biology approaches, we found surprising roles for EGFR family members, sex steroid hormone receptor ESR1 interplay with oncogenic STAT function and proposed new drug targeting approaches of oncogenic STAT pathway addiction.


Asunto(s)
Neoplasias , Factores de Transcripción STAT , Citocinas/metabolismo , Receptores ErbB/metabolismo , Humanos , Neoplasias/genética , Factores de Transcripción STAT/genética , Factores de Transcripción STAT/metabolismo
4.
J Ethnopharmacol ; 285: 114840, 2022 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-34800646

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: As a traditional Chinese formula, Liujunzi Decoction (LJZD) originated from the Yi Xue Zheng Zhuan, and has a promising effect in treating chemotherapy-induced anorexia (CIA). AIM OF THE STUDY: The present study aims to investigate whether LJZD acts on interleukin-6 (IL-6)/leptin mediated janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway that regulates hypothalamus anorexigenic and orexigenic peptides to ameliorate CIA, and also elucidates the potential mechanism by metabolomic analysis. MATERIALS AND METHODS: Network pharmacology analyses were conducted to screen out potential targets and pathways. The CIA rat model was established via an intraperitoneal injection of cisplatin. The histological changes of gastric antrum, liver and ileum were observed by HE staining. The serum levels of leptin, ghrelin, IL-6 and growth differentiation factor 15 (GDF15) were measured by ELISA. The JAK1/2 and STAT levels in gastric antrum and hypothalamus were detected by Western blot. The transcriptions of gastric antrum and hypothalamus IL-6R mRNA, and hypothalamus cocaine- and amphetamine-regulated transcript (CART), pro-opiomelanocortin (POMC), thyrotropin-releasing hormone (TRH), upregulated orexigenic peptides neuropeptide Y (NPY), and agouti-related protein (AGRP) mRNA were assessed by RT-qPCR. The blood samples of control, model and high dose LJZD groups were analyzed by metabolomic. RESULTS: Network pharmacology highlighted the IL-6/leptin mediated JAK-STAT signaling pathway, which regulated downstream anorexigenic and orexigenic peptides in hypothalamus. LJZD ameliorated CIA via stimulating food intake and water consumption in rats. Cisplatin-induced gastric antrum, liver, ileum injuries were ameliorated, serum leptin level reduction was elevated, and ghrelin, IL-6, GDF15 level increases were decreased after LJZD treatments. In gastric antrum and hypothalamus, LJZD inhibited cisplatin-induced activation of JAK-STAT signaling pathway, downregulated the transcriptions of downstream anorexigenic peptides CART, POMC, TRH, and upregulated orexigenic peptides NPY, AGRP in hypothalamus. Importantly, the effect of LJZD in treating CIA might partly relate to the improvements of 23 abnormal metabolites. CONCLUSION: This study implies that inhibiting JAK-STAT signaling pathway, regulating the expressions of anorexigenic and orexigenic peptides, and mediating various metabolic pathways might be potential mechanisms of LJZD's effect against CIA.


Asunto(s)
Anorexia/tratamiento farmacológico , Cisplatino/toxicidad , Medicamentos Herbarios Chinos/uso terapéutico , Quinasas Janus/metabolismo , Fitoterapia , Factores de Transcripción STAT/metabolismo , Animales , Anorexia/inducido químicamente , Antineoplásicos/toxicidad , Regulación de la Expresión Génica/efectos de los fármacos , Quinasas Janus/genética , Masculino , Simulación del Acoplamiento Molecular , Farmacología en Red , Neuropéptidos/genética , Neuropéptidos/metabolismo , Oligopéptidos/genética , Oligopéptidos/metabolismo , Ácido Pirrolidona Carboxílico/análogos & derivados , Ácido Pirrolidona Carboxílico/metabolismo , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Factores de Transcripción STAT/genética , Transducción de Señal/efectos de los fármacos
5.
Bioengineered ; 12(2): 12461-12469, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34931923

RESUMEN

Severe mortality due to the COVID-19 pandemic resulted from the lack of effective treatment. Although COVID-19 vaccines are available, their side effects have become a challenge for clinical use in patients with chronic diseases, especially cancer patients. In the current report, we applied network pharmacology and systematic bioinformatics to explore the use of biochanin A in patients with colorectal cancer (CRC) and COVID-19 infection. Using the network pharmacology approach, we identified two clusters of genes involved in immune response (IL1A, IL2, and IL6R) and cell proliferation (CCND1, PPARG, and EGFR) mediated by biochanin A in CRC/COVID-19 condition. The functional analysis of these two gene clusters further illustrated the effects of biochanin A on interleukin-6 production and cytokine-cytokine receptor interaction in CRC/COVID-19 pathology. In addition, pathway analysis demonstrated the control of PI3K-Akt and JAK-STAT signaling pathways by biochanin A in the treatment of CRC/COVID-19. The findings of this study provide a therapeutic option for combination therapy against COVID-19 infection in CRC patients.


Asunto(s)
Anticarcinógenos/uso terapéutico , Antivirales/uso terapéutico , Tratamiento Farmacológico de COVID-19 , Neoplasias Colorrectales/tratamiento farmacológico , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Genisteína/uso terapéutico , Fitoestrógenos/uso terapéutico , Atlas como Asunto , COVID-19/inmunología , COVID-19/patología , COVID-19/virología , Neoplasias Colorrectales/inmunología , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/virología , Ciclina D1/genética , Ciclina D1/inmunología , Receptores ErbB/genética , Receptores ErbB/inmunología , Humanos , Interleucina-1alfa/genética , Interleucina-1alfa/inmunología , Interleucina-2/genética , Interleucina-2/inmunología , Quinasas Janus/genética , Quinasas Janus/inmunología , Redes y Vías Metabólicas/efectos de los fármacos , Redes y Vías Metabólicas/genética , Terapia Molecular Dirigida/métodos , Familia de Multigenes , Farmacología en Red/métodos , PPAR gamma/genética , PPAR gamma/inmunología , Farmacogenética/métodos , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/inmunología , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/inmunología , Receptores de Interleucina-6/genética , Receptores de Interleucina-6/inmunología , SARS-CoV-2/efectos de los fármacos , SARS-CoV-2/crecimiento & desarrollo , SARS-CoV-2/patogenicidad , Factores de Transcripción STAT/genética , Factores de Transcripción STAT/inmunología , Transducción de Señal
6.
J Ethnopharmacol ; 275: 114132, 2021 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-33887419

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Alpinia galanga, commonly known as greater galangal or raasna, is widely used in Ayurveda against various inflammatory disorders. It is also known as Kulinjan, Aratha, Rasna or Sugandhamula. Some of the Ayurvedic preparations using the rhizome of Alpinia galanga are Rasnadi kashayam, Rasna panchakam, Rasnapthakam, and Rasnarendadi. The aromatic rhizome is the source of the drug greater galangal and it is also used as a spice in South and South East Asia. However, the molecular mechanism of action of A galanga against inflammation remains poorly understood. AIM OF THE STUDY: To elucidate the anti-inflammatory effect of hydroalcoholic extract of Alpinia galanga rhizome. STUDY DESIGN/METHOD: The mechanism of the anti-inflammatory effect of hydroalcoholic extract of Alpinia galanga (AGE) was investigated by enzyme-linked immunosorbent assay (ELISA), Western blot, and immunofluorescence in LPS stimulated murine macrophage cell line (RAW 264.7). HPLC analysis was done to elucidate the rich polyphenolic nature of AGE. RESULTS: The study showed that pre-treatment with AGE downregulated the release of pro-inflammatory mediators (IL-6, TNF-α, NO, and ROS) and stimulated the release of anti-inflammatory mediator IL-10 in LPS stimulated RAW 264.7 cells. The vital enzymes of inflammation (iNOS, COX-2, and MMP-9) were also downregulated by pre-treatment with AGE. AGE targeted the upstream elements of the inflammatory cascade by blocking LPS induced activation of TLR4 and JAK/STAT pathway. The phosphorylation of downstream kinases was significantly affected. The inhibition of nuclear translocation of NFκB further confirmed the specific inhibition of the TLR4 pathway. Particularly AGE inhibited the phosphorylation of JNK, p38, IκBα, and STAT. HPLC analysis of the AGE showed the polyphenol-rich nature of the extract. CONCLUSIONS: The results from this study provide firm evidence that AGE exerts its anti-inflammatory effect via modulation of TLR4 and JAK/STAT pathway.


Asunto(s)
Alpinia/química , Quinasas Janus/genética , Factor 88 de Diferenciación Mieloide/genética , Extractos Vegetales/farmacología , Factores de Transcripción STAT/genética , Receptor Toll-Like 4/genética , Proteínas Quinasas p38 Activadas por Mitógenos/genética , Animales , Antiinflamatorios/química , Antiinflamatorios/farmacología , Supervivencia Celular/efectos de los fármacos , Ciclooxigenasa 2/metabolismo , Citocinas/metabolismo , Regulación hacia Abajo/efectos de los fármacos , Gelatinasas/metabolismo , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Quinasas Janus/metabolismo , Lipopolisacáridos/toxicidad , Metaloproteinasa 9 de la Matriz/metabolismo , Ratones , Factor 88 de Diferenciación Mieloide/metabolismo , FN-kappa B/antagonistas & inhibidores , FN-kappa B/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , Extractos Vegetales/química , Células RAW 264.7 , Especies Reactivas de Oxígeno/metabolismo , Rizoma/química , Factores de Transcripción STAT/metabolismo , Transducción de Señal/efectos de los fármacos , Receptor Toll-Like 4/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo
7.
Artículo en Inglés | MEDLINE | ID: mdl-33749513

RESUMEN

This study analyzed the effects of the plant extracts (Citrus limon, Solanum lycopersicum, Zingiber officinale, Vitis vinifera and Allium sativum) on the growth of mammalian cells (Vero and MDA-MB-231) and evaluated the most effective plant extract for the expression of specific genes of the JAK/STAT pathway in human breast cancer cells. An antiproliferative bioassay involving neutral red-dye uptake was used to determine the anticancerous potential of plant extracts. In Vero cells, the ginger methanolic extract was least effective; whereas the lemon methanolic extract was more effective with 64 dilutions with IC50 51.42%. In MDA-MB-231 cells, the tomato and ginger methanolic, and grape water extracts were least effective, whereas lemon water extract was most effective with 32 dilutions with IC50 48.67%, by upregulating JAK1, JAK2, TYK2, IRF7 and IRF3 gene expressions of the JAK/STAT pathway. C. limon inhibited the growth of both Vero and MDA-MB 231 cells. It suggested that C. limon has anti-cancer potential by inducing the JAK/STAT pathway.


Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Citrus/química , Quinasas Janus/genética , Extractos Vegetales/farmacología , Factores de Transcripción STAT/genética , Animales , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Chlorocebus aethiops , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Quinasas Janus/metabolismo , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Factores de Transcripción STAT/metabolismo , Células Vero
8.
Funct Integr Genomics ; 20(3): 343-353, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-31659573

RESUMEN

Evidence from biochemical liver function index and histopathology analysis suggested that selenium could effectively repair the liver injury caused by beta-cypermethrin (ß-CYP). However, the molecular mechanism of selenium against liver injury induced by ß-CYP remains unclear. In the present study, dynamic changes in gene expression profiles before and after the treatment of Na2SeO3 in liver injury mice were analyzed by using RNA sequencing. As a result, several essential genes and pathways were identified to be significantly associated with this process. In particular, ten genes including Cyp2j11, Cyp2b10, Cyp3a13, Dhrs9, Socs2, Stat4, Gm13305, Cyp3a44, Retsat, and Cyp26b1 were significantly enriched in the functional categories related to retinol metabolism, linoleic acid metabolism, and Jak-STAT signaling pathway. Among them, the expression patterns of nine genes were validated by qRT-PCR, except for Cyp3a44. Furthermore, we have constructed the associated regulatory network based on the identified targets revealed by high throughput screening. Our study may provide insight into the molecular mechanism underlying the protective effect of selenium against liver injury induced by ß-CYP in mammals.


Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas/genética , Hígado/metabolismo , Selenio/farmacología , Transcriptoma , Animales , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Sistema Enzimático del Citocromo P-450/genética , Sistema Enzimático del Citocromo P-450/metabolismo , Insecticidas/toxicidad , Quinasas Janus/genética , Quinasas Janus/metabolismo , Hígado/efectos de los fármacos , Ratones , Piretrinas/toxicidad , Factores de Transcripción STAT/genética , Factores de Transcripción STAT/metabolismo , Selenio/uso terapéutico
9.
Cells ; 8(10)2019 09 27.
Artículo en Inglés | MEDLINE | ID: mdl-31569788

RESUMEN

The current treatment options for inflammatory bowel disease (IBD) are unsatisfactory. Therefore, novel and safer therapies are needed. We previously reported that koreanaside A (KA) showed high radical scavenging activity and suppressed vascular cell adhesion molecule 1 (VCAM-1) expression in vascular smooth muscle cells. However, the molecular mechanisms involved in its anti-inflammatory effect have not been reported. KA inhibited pro-inflammatory mediators such as inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), nitric oxide (NO), and prostaglandin E2 (PGE2). KA inhibited the production and mRNA expression of interleukin (IL)-6 and tumor necrosis factor-α (TNF-α) induced by LPS. KA downregulated the myeloid differentiation primary response 88 (MyD88)-dependent inflammatory gene expressions in the MyD88-overexpressed cells. KA suppressed the LPS-induced transcriptional and DNA-binding activities of activator protein-1 (AP-1) and nuclear factor-kappa B (NF-κB). KA was found to inhibit the phosphorylation of Janus kinase 1/2 (JAK1/2) and signal transducers and activators of transcription 1/3 (STAT1/3). In DSS-induced colitis mice, KA relieved the symptoms of colitis by suppressing inflammatory cell infiltration, restoring tight junction (TJ)- and epithelial-mesenchymal transition (EMT)-related protein expression, and inactivating AP-1, NF-κB, and STAT1/3. Therefore, KA reduced inflammatory responses by downregulating AP-1, NF-κB, and JAK/STAT signaling in LPS-induced macrophages and DSS-induced colitis mice.


Asunto(s)
Antiinflamatorios/farmacología , Colitis/tratamiento farmacológico , Regulación de la Expresión Génica/efectos de los fármacos , Glicósidos/farmacología , Lignanos/química , Lignanos/farmacología , Activación de Macrófagos/efectos de los fármacos , Extractos Vegetales/farmacología , Animales , Antiinflamatorios/aislamiento & purificación , Colitis/inducido químicamente , Colitis/metabolismo , Colitis/patología , Sulfato de Dextran/toxicidad , Flores/química , Forsythia/química , Glicósidos/aislamiento & purificación , Janus Quinasa 1/genética , Janus Quinasa 1/metabolismo , Lignanos/aislamiento & purificación , Lipopolisacáridos/farmacología , Masculino , Ratones , Ratones Endogámicos C57BL , FN-kappa B/genética , FN-kappa B/metabolismo , Células RAW 264.7 , Factores de Transcripción STAT/genética , Factores de Transcripción STAT/metabolismo , Transducción de Señal , Factor de Transcripción AP-1/genética , Factor de Transcripción AP-1/metabolismo
10.
BMC Complement Altern Med ; 19(1): 264, 2019 Oct 07.
Artículo en Inglés | MEDLINE | ID: mdl-31590658

RESUMEN

BACKGROUND: Osteoarthritis (OA) is a common degenerative disease of synovial joints caused by inflammation. Acteoside (ACT), a major component and lipase inhibitor from the Chinese tea Ligustrum purpurascens kudingcha, has been reported to regulate the inflammation and immune response. The study aims to investigate the effects of ACT on inflammatory responses and joint protection in OA rats. METHODS: Cell proliferation was examined by MTT and colony formation assay. Apoptosis was analyzed using flow cytometry with Annexin V/PI staining. ELISA was employed to examine the concentration of inflammatory cytokines. OA rat model was established by surgery stimulation. RESULTS: ACT treatment significantly inhibited the upregulation of inflammatory cytokines induced by IL-1ß in primary chondrocytes, including IL-6, IL-12, TNF-α and IFN-γ. ACT stimulation also enhanced the cell proliferation, while inhibited cell apoptosis in IL-1ß-treated chondrocytes. Consistently, ACT treatment led to downregulation of cleaved-caspase-3 and apoptosis regulator Bax, and upregulation of Bcl-2. Furthermore, ACT treatment inhibited IL-1ß-induced activation of JAK/STAT pathway. The results were confirmed in surgery-induced OA rat model. Moreover, ACT treatment significantly inhibited synovial inflammation and articular chondrocyte apoptosis in OA rats. CONCLUSION: Our findings indicate that ACT has the potential therapeutic effect on OA through inhibiting the inflammatory responses via inactivating JAK/STAT signaling pathway.


Asunto(s)
Medicamentos Herbarios Chinos/administración & dosificación , Glucósidos/administración & dosificación , Ligustrum/química , Osteoartritis/tratamiento farmacológico , Fenoles/administración & dosificación , Animales , Proliferación Celular/efectos de los fármacos , Condrocitos , Modelos Animales de Enfermedad , Humanos , Interferón gamma/genética , Interferón gamma/inmunología , Quinasas Janus/genética , Quinasas Janus/inmunología , Masculino , Osteoartritis/genética , Osteoartritis/inmunología , Ratas , Ratas Sprague-Dawley , Factores de Transcripción STAT/genética , Factores de Transcripción STAT/inmunología , Transducción de Señal/efectos de los fármacos , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/inmunología
11.
Infect Genet Evol ; 75: 103981, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-31369863

RESUMEN

Peste des petits ruminants virus (PPRV) is a morbillivirus which causes severe disease in ruminants. Since interferons (IFNs) serve as the important defense line against viral infection, we have investigated the roles of types I and III IFNs in PPRV infection in vitro. Upon PPRV infection, IFN-λ3 was strongly induced, while IFN-ß and IFN-λ2 were moderately induced at transcriptional level in human embryonic kidney 293 T (HEK293T) cells. Although the transcription of type I and III IFNs were triggered, the production of functional IFN products was not detected. Importantly, the replication of PPRV was strongly inhibited in HEK293T cells treated by the exogenous IFNs (IFN-α-2b, IFN-ß and IFN-λ3). Consistently, these IFNs significantly activate a panel of IFN-stimulated genes (ISGs). The inhibition of JAK-STAT pathway by JAK I inhibitor can abrogate the anti-PPRV activity of IFNs. Thus, our study shall contribute to better understanding of the complex PPRV-host interactions and provide rationale for therapeutic development of IFN-based treatment against PPRV infection.


Asunto(s)
Interferones/genética , Interferones/farmacología , Peste de los Pequeños Rumiantes/genética , Virus de la Peste de los Pequeños Rumiantes/fisiología , Animales , Regulación de la Expresión Génica/efectos de los fármacos , Células HEK293 , Interacciones Microbiota-Huesped , Humanos , Quinasas Janus/genética , Peste de los Pequeños Rumiantes/tratamiento farmacológico , Peste de los Pequeños Rumiantes/virología , Virus de la Peste de los Pequeños Rumiantes/efectos de los fármacos , Factores de Transcripción STAT/genética , Transducción de Señal/efectos de los fármacos , Replicación Viral/efectos de los fármacos
12.
Med Sci Monit ; 25: 4923-4932, 2019 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-31268042

RESUMEN

Thyroid-associated ophthalmopathy is the commonest orbital disease in adults. However, shortcomings still exist in treatments. The aim of this study was to identify the efficacy and potential mechanism of gypenosides in the treatment of thyroid-associated ophthalmopathy. The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform was screened for active compounds of gypenosides, and targets were predicted using Swiss Target Prediction. The targets of thyroid-associated ophthalmopathy were obtained from Online Mendelian Inheritance in Man, Comparative Toxicogenomic Database and GeneCards Human gene database. Gene Ontology (GO), the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Reactome Pathways were determined based on the common targets. Protein-protein interaction (PPI) network was constructed to further understand of relationship among target genes, compounds and proteins. Molecular docking was performed to investigate the binding ability between gypenosides and hub genes. A total of 70 targets for gypenosides and 804 targets for thyroid-associated ophthalmopathy were obtained with 8 common targets identified. GO analysis and KEGG pathway analysis revealed that the hub genes were enriched in JAK-STAT, while Reactome pathways analysis indicated genes enriched in interleukin pathways. PPI network showed STAT1, STAT3, and STAT4 were at the center. Additionally, molecular docking indicated that STAT1 and STAT3 display good binding forces with gypenosides. This study indicates that target genes mainly enriched in JAK-STAT signaling pathway, particularly in STATs, which can be combined with gypenosides. This may suggest that gypenosides have curative effect on thyroid-associated ophthalmopathy via the JAK-STAT pathway.


Asunto(s)
Biología Computacional/métodos , Oftalmopatía de Graves/tratamiento farmacológico , Perfilación de la Expresión Génica/métodos , Regulación Neoplásica de la Expresión Génica/genética , Ontología de Genes , Redes Reguladoras de Genes/genética , Oftalmopatía de Graves/genética , Oftalmopatía de Graves/metabolismo , Gynostemma/metabolismo , Humanos , Medicina Tradicional China , Simulación del Acoplamiento Molecular/métodos , Extractos Vegetales/metabolismo , Extractos Vegetales/uso terapéutico , Mapas de Interacción de Proteínas/genética , Factores de Transcripción STAT/genética , Factores de Transcripción STAT/metabolismo , Transducción de Señal/genética
13.
J Food Drug Anal ; 25(4): 908-918, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-28987368

RESUMEN

Recent investigations have demonstrated that carotenoid extract of Dunaliella salina alga (Alga) contains abundant ß-carotene and has good anti-inflammatory activities. Murine macrophage (RAW264.7 cells) was used to establish as an in vitro model of pseudorabies virus-induced reactive oxygen species (ROS) response. In this study, antioxidant activities of Alga were measured based on 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, trolox equivalent antioxidant capacity assays, reducing power, and virus-induced ROS formation in RAW264.7 cells. Anti-inflammatory activities of Alga were assessed by its ability to inhibit the production of interleukin-6 and nitric oxide (NO) using enzyme-linked immunosorbent assay, then the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway was investigated by measuring the inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), nuclear factor-κB (p50 and p65), JAK, STAT-1/3, and suppressor of cytokine signaling 3 (SOCS3) by Western blotting. In addition, Alga inhibited virus replication by plaque assay. Our results showed that the Alga had high antioxidant activity, significantly reduced the virus-induced accumulation of ROS, and inhibited the levels of nitric oxide and interleukin-6. Further studies revealed that Alga also downregulated the gene and protein expressions of iNOS, COX-2, nuclear factor-κB (p50 and p65), and the JAK/STAT pathway. The inhibitory effects of Alga were similar to pretreatment with specific inhibitors of JAK and STAT-3 in pseudorabies virus -infected RAW264.7 cells. Alga enhanced the expression of SOCS3 to suppress the activity of the JAK/STAT signaling pathway in pseudorabies virus-infected RAW264.7 cells. In addition, Alga has decreased viral replication (p < 0.005) at an early stage. Therefore, our results demonstrate that Alga inhibits ROS, interleukin6, and nitric oxide production via suppression of the JAK/STAT pathways and enhanced the expression of SOCS3 in virus-infected RAW264.7 cells.


Asunto(s)
Chlorophyta/química , Interleucina-6/metabolismo , Quinasas Janus/metabolismo , Macrófagos/efectos de los fármacos , FN-kappa B/metabolismo , Óxido Nítrico/metabolismo , Extractos Vegetales/farmacología , Especies Reactivas de Oxígeno/metabolismo , Animales , Herpesvirus Suido 1/fisiología , Interleucina-6/genética , Quinasas Janus/genética , Macrófagos/metabolismo , Macrófagos/virología , Ratones , FN-kappa B/genética , Seudorrabia/genética , Seudorrabia/metabolismo , Seudorrabia/virología , Células RAW 264.7 , Factores de Transcripción STAT/genética , Factores de Transcripción STAT/metabolismo , Transducción de Señal
14.
Biofactors ; 43(3): 388-399, 2017 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-28139053

RESUMEN

Ze339, an herbal extract from Petasites hybridus leaves is effective in treatment of allergic rhinitis by inhibition of a local production of IL-8 and eicosanoid LTB4 in allergen-challenged patients. However, the mechanism of action and anti-inflammatory potential in virally induced exacerbation of the upper airways is unknown. This study investigates the anti-inflammatory mechanisms of Ze339 on primary human nasal epithelial cells (HNECs) upon viral, bacterial and pro-inflammatory triggers. To investigate the influence of viral and bacterial infections on the airways, HNECs were stimulated with viral mimics, bacterial toll-like-receptor (TLR)-ligands or cytokines, in presence or absence of Ze339. The study uncovers Ze339 modulated changes in pro-inflammatory mediators and decreased neutrophil chemotaxis as well as a reduction of the nuclear translocation and phosphorylation of STAT molecules. Taken together, this study suggests that phyto drug Ze339 specifically targets STAT-signalling pathways in HNECs and has high potential as a broad anti-inflammatory drug that exceeds current indication. © 2016 BioFactors, 43(3):388-399, 2017.


Asunto(s)
Células Epiteliales/efectos de los fármacos , Petasites/química , Extractos Vegetales/farmacología , Factores de Transcripción STAT/antagonistas & inhibidores , Sesquiterpenos/farmacología , Movimiento Celular/efectos de los fármacos , Quimiocinas/antagonistas & inhibidores , Quimiocinas/biosíntesis , Células Epiteliales/citología , Células Epiteliales/metabolismo , Flagelina/antagonistas & inhibidores , Flagelina/farmacología , Regulación de la Expresión Génica , Humanos , Interferón gamma/antagonistas & inhibidores , Interferón gamma/farmacología , Interleucina-4/antagonistas & inhibidores , Interleucina-4/farmacología , Lipopéptidos/antagonistas & inhibidores , Lipopéptidos/farmacología , Cavidad Nasal/citología , Cavidad Nasal/efectos de los fármacos , Cavidad Nasal/metabolismo , Neutrófilos/efectos de los fármacos , Hojas de la Planta/química , Poli I-C/antagonistas & inhibidores , Poli I-C/farmacología , Cultivo Primario de Células , Factores de Transcripción STAT/genética , Factores de Transcripción STAT/metabolismo , Transducción de Señal
15.
Int Immunopharmacol ; 39: 79-83, 2016 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-27449327

RESUMEN

The aim of this study was to detect the therapeutic effect of dioscin on collagen-induced arthritis (CIA). Mice model of CIA was induced by chicken collagen II and arthritis index was assessed. After suspension of dioscin (100mg/kg/d) or triptolide was intragastrically administered, the left paw swelling and body weight of each mouse were measured. Then tissue samples were assayed by histopathological analysis. The levels of Th1 and Th2 were detected by flow cytometry. The expression of p-STAT1, p-STAT4 and p-STAT6 was demonstrated by western blot analysis, and T-bet and GATA-3 expression was detected by RT-PCR. The paw swelling and arthritis index were decreased and body weight was increased in the high dose of dioscin group compared to the model group (P<0.05). Histopathological analysis revealed that the damage of synovium tissue in dioscin and triptolide group alleviated. The ratio of Th1/Th2 in the dioscin group (0.82±0.24) and triptolide group (0.99±0.44) was lower than that in the model group (1.84±0.70, P<0.05). Additionally, p-STAT4 expression was decreased, and both p-STAT6 and GATA3 expression was increased in the dioscin group than that in the model group (P<0.05). Dioscin might have some therapeutic effects on CIA through regulating the proportion of Th1/Th2 cells, which could reduce the expression of p-STAT4, increase the expression of p-STAT6 and GATA3 in the synovial tissue.


Asunto(s)
Antiinflamatorios/uso terapéutico , Artritis Experimental/tratamiento farmacológico , Dioscorea/inmunología , Diosgenina/análogos & derivados , Membrana Sinovial/efectos de los fármacos , Células TH1/efectos de los fármacos , Células Th2/efectos de los fármacos , Animales , Colágeno Tipo II/inmunología , Diosgenina/uso terapéutico , Modelos Animales de Enfermedad , Diterpenos/uso terapéutico , Compuestos Epoxi/uso terapéutico , Factor de Transcripción GATA3/genética , Factor de Transcripción GATA3/metabolismo , Humanos , Masculino , Ratones , Ratones Endogámicos DBA , Fenantrenos/uso terapéutico , Factores de Transcripción STAT/genética , Factores de Transcripción STAT/metabolismo , Membrana Sinovial/patología , Células TH1/inmunología , Balance Th1 - Th2/efectos de los fármacos , Células Th2/inmunología
16.
Sci Rep ; 5: 9395, 2015 Mar 23.
Artículo en Inglés | MEDLINE | ID: mdl-25797918

RESUMEN

Traditional Chinese Medicine (TCM) treatment has been commonly used to treat Chronic Hepatitis B (CHB) in Asian countries based on TCM syndrome diagnosis, also called "ZHENG". The syndrome is identified through the four-diagnostic methods, with certain degree of subjectivity and ambiguity from individual doctors. Normally those CHB patients also receive series of parameters from modern clinical examination, while they are routinely believed to be unrelated with the TCM syndrome diagnosis. In this study, we investigated whether these biomedical indexes in modern medicine could be beneficial to TCM syndrome diagnostics in an integrative way. Based on 634 patient samples from health controls and three subtypes of CHB syndromes, a two-view based hierarchical classification model was tested for TCM syndromes prediction based on totally 222 parameters integrated from both TCM practice and modern clinical tests. The results indicated that the performance of syndrome classification based on a proper integration of TCM and modern clinical indexes was significantly higher than those based on one view of parameters only. Furthermore, those indexes correlated with CHB syndrome diagnosis were successfully identified for CM indexes and biochemical indexes respectively, where potential associations between them were hinted to the MAPK signaling pathway.


Asunto(s)
Virus de la Hepatitis B/patogenicidad , Hepatitis B Crónica/diagnóstico , Medicina Tradicional China/métodos , Modelos Estadísticos , Evaluación de Síntomas/estadística & datos numéricos , Algoritmos , Biomarcadores/análisis , Regulación de la Expresión Génica , Virus de la Hepatitis B/genética , Hepatitis B Crónica/genética , Hepatitis B Crónica/patología , Hepatitis B Crónica/virología , Interacciones Huésped-Patógeno , Humanos , Sistema de Señalización de MAP Quinasas , Proteínas Quinasas Activadas por Mitógenos/genética , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Factores de Transcripción STAT/genética , Factores de Transcripción STAT/metabolismo , Síndrome
17.
J Infect Dis ; 212(4): 635-44, 2015 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-25612733

RESUMEN

Vitamin D level is linked to susceptibility to infections, but its relevance in candidemia is unknown. We aimed to investigate the in vivo sequelae of vitamin D3 supplementation in systemic Candida infection. Implicating the role of vitamin D in Candida infections, we showed that candidemic patients had significantly lower 25-OHD concentrations. Candida-infected mice treated with low-dose 1,25(OH)2D3 had reduced fungal burden and better survival relative to untreated mice. Conversely, higher 1,25(OH)2D3 doses led to poor outcomes. Mechanistically, low-dose 1,25(OH)2D3 induced proinflammatory immune responses. This was mediated through suppression of SOCS3 and induction of vitamin D receptor binding with the vitamin D-response elements in the promoter of the gene encoding interferon γ. These beneficial effects were negated with higher vitamin D3 doses. While the antiinflammatory effects of vitamin D3 are well described, we found that, conversely, lower doses conferred proinflammatory benefits in Candida infection. Our study highlights caution against extreme deviations of vitamin D levels during infections.


Asunto(s)
Candidiasis/tratamiento farmacológico , Colecalciferol/farmacología , Vitamina D/sangre , Animales , Candidiasis/inmunología , Colecalciferol/administración & dosificación , Estudios de Cohortes , Relación Dosis-Respuesta a Droga , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Inflamación/inmunología , Inflamación/metabolismo , Interferón gamma/metabolismo , Leucocitos Mononucleares , Ratones , Ratones Endogámicos BALB C , Regiones Promotoras Genéticas , ARN Mensajero/genética , ARN Mensajero/metabolismo , Factores de Transcripción STAT/genética , Factores de Transcripción STAT/metabolismo , Proteína 3 Supresora de la Señalización de Citocinas , Proteínas Supresoras de la Señalización de Citocinas/genética , Proteínas Supresoras de la Señalización de Citocinas/metabolismo
18.
Planta Med ; 80(8-9): 614-21, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24853762

RESUMEN

Diabetic nephropathy is one of the most significant microvascular complications associated with diabetes. Until now, there is no effective treatment and the gene mechanism of diabetic nephropathy is still unclear. Tangshen formula is a traditional Chinese medicine, and has been shown to have good clinical efficacy in diabetic nephropathy treatment. The objective of this study was to investigate the changes of gene expression profiling and explore the molecular mechanism using a db/db mice model treated by Tangshen formula. After administration for 12 weeks, a microarray was applied to detect the gene expression of db/db mice kidney tissues. Quantitative real-time PCR was used to confirm the differential gene expression and carry out a JAK/STAT/SOCS signaling pathway study. Treatment with Tangshen formula reduced the levels of serum glucose and urinary albumin in db/db mice, and the effects of Tangshen formula on db/db mice were significantly different from the positive control (Losartan potassium tablets) on microarray data. It also showed that the JAK/STAT/SOCS signaling pathway played an important role in the treatment process. The expressions of JAK1, JAK2, and STAT3 were upregulated, and STAT4 was downregulated in Tangshen formula-treated db/db mice. SOCS1, 3, and 7 were all activated, while negative feedback regulated other related genes in the JAK/STAT/SOCS pathway. Our study suggested that Tangshen formula has beneficial effects on diabetic nephropathy treatment via regulating the JAK/STAT/SOCS signaling pathway. This study will help to provide evidence-based recommendations for Tangshen formula clinical treatment.


Asunto(s)
Nefropatías Diabéticas/tratamiento farmacológico , Medicamentos Herbarios Chinos/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Plantas Medicinales/química , Transducción de Señal/efectos de los fármacos , Animales , Análisis por Conglomerados , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos/aislamiento & purificación , Perfilación de la Expresión Génica , Quinasas Janus/genética , Riñón/efectos de los fármacos , Masculino , Medicina Tradicional China , Ratones , Análisis de Secuencia por Matrices de Oligonucleótidos , Reacción en Cadena en Tiempo Real de la Polimerasa , Factores de Transcripción STAT/genética , Proteínas Supresoras de la Señalización de Citocinas/genética
19.
Mol Biol Rep ; 41(7): 4583-94, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24604727

RESUMEN

A hallmark of cancer is resistance to apoptosis, with both the loss of proapoptotic signals and the gain of anti-apoptotic mechanisms contributing to tumorigenesis. As inducing apoptosis in malignant cells is one of the most challenging tasks regarding cancer, researchers increasingly focus on natural products to regulate apoptotic signaling pathways. Curcumin, a polyphenolic derivative of turmeric, is a natural compound derived from Curcuma longa, has attracted great interest in the research of cancer during the last half century. Extensive studies revealed that curcumin has chemopreventive properties, which are mainly due to its ability to arrest cell cycle and to induce apoptosis in cancer cells either alone or in combination with chemotherapeutic agents or radiation. The underlying action mechanisms of curcumin are diverse and has not been elucidated so far. By regulating multiple important cellular signalling pathways including NF-κB, TRAIL, PI3 K/Akt, JAK/STAT, Notch-1, JNK, etc., curcumin are known to activate cell death signals and induce apoptosis in pre-cancerous or cancer cells without affecting normal cells, thereby inhibiting tumor progression. Several phase I and phase II clinical trials indicate that curcumin is quite safe and may exhibit therapeutic efficacy. This article reviews the main effects of curcumin on the different apoptotic signaling pathways involved in curcumin induced apoptosis in cancer cells via cellular transduction pathways and provides an in depth assessment of its pharmacological activity in the management of tumor progression.


Asunto(s)
Antineoplásicos Fitogénicos/uso terapéutico , Curcumina/uso terapéutico , Regulación Neoplásica de la Expresión Génica , Neoplasias/tratamiento farmacológico , Apoptosis/efectos de los fármacos , Proteínas Reguladoras de la Apoptosis/genética , Proteínas Reguladoras de la Apoptosis/metabolismo , Línea Celular Tumoral , Ensayos Clínicos como Asunto , Humanos , FN-kappa B/genética , FN-kappa B/metabolismo , Neoplasias/genética , Neoplasias/metabolismo , Neoplasias/patología , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Factores de Transcripción STAT/genética , Factores de Transcripción STAT/metabolismo , Transducción de Señal , Ligando Inductor de Apoptosis Relacionado con TNF/genética , Ligando Inductor de Apoptosis Relacionado con TNF/metabolismo
20.
J Anim Physiol Anim Nutr (Berl) ; 98(1): 84-95, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-23402545

RESUMEN

The objective of the study was to investigate selected key regulatory pathways of milk protein biosynthesis in primary bovine mammary epithelial cells (MECs) of dairy cows during the first 155 days of lactation. In addition, cows were exposed to feed restriction for a short period (FR) during different stages of lactation (week 4 and 21 pp) to study adjustment processes of molecular protein biosynthesis to metabolic challenge. Morning milk samples from twenty-four Holstein-Friesian cows were collected throughout the experimental period (n = 10 per animal). MEC from raw milk were purified using an immunomagnetic separation technique and used for real-time quantitative PCR analyses. As was seen in transcript abundances of all major milk proteins, mRNA levels of E74-like factor 5 (ELF5), an enhancer of signal transducer and activator of transcription (STAT) action, concomitantly decreased towards mid-lactation. Expression of ELF5 as well as of all milk protein genes showed a similar increase during FR in early lactation. Occasional changes in expression could be seen in other Janus kinase (JAK)/STAT factors and in mammalian target of rapamycin (mTOR) pathway elements. Amino acid transfer and glucose transporter and the ß-casein expression were also partially affected. In conclusion, our findings suggest a pivotal role of the transcription factor ELF5 in milk protein mRNA expression with complementary JAK/STAT and mTOR signalling for the regulation of protein biosynthesis in the bovine mammary gland.


Asunto(s)
Células Epiteliales/metabolismo , Privación de Alimentos/fisiología , Regulación de la Expresión Génica/fisiología , Lactancia/fisiología , Glándulas Mamarias Animales/citología , Leche/citología , Aminoácidos/metabolismo , Alimentación Animal/análisis , Animales , Transporte Biológico , Bovinos , Dieta/veterinaria , Femenino , Proteínas Facilitadoras del Transporte de la Glucosa/genética , Proteínas Facilitadoras del Transporte de la Glucosa/metabolismo , Quinasas Janus/genética , Quinasas Janus/metabolismo , Leche/química , ARN Mensajero/genética , ARN Mensajero/metabolismo , Factores de Transcripción STAT/genética , Factores de Transcripción STAT/metabolismo , Serina-Treonina Quinasas TOR/genética , Serina-Treonina Quinasas TOR/metabolismo
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