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1.
Sci China Life Sci ; 67(5): 1010-1026, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38489007

RESUMO

Alveolar bone regeneration has been strongly linked to macrophage polarization. M1 macrophages aggravate alveolar bone loss, whereas M2 macrophages reverse this process. Berberine (BBR), a natural alkaloid isolated and refined from Chinese medicinal plants, has shown therapeutic effects in treating metabolic disorders. In this study, we first discovered that culture supernatant (CS) collected from BBR-treated human bone marrow mesenchymal stem cells (HBMSCs) ameliorated periodontal alveolar bone loss. CS from the BBR-treated HBMSCs contained bioactive materials that suppressed the M1 polarization and induced the M2 polarization of macrophages in vivo and in vitro. To clarify the underlying mechanism, the bioactive materials were applied to different animal models. We discovered macrophage colony-stimulating factor (M-CSF), which regulates macrophage polarization and promotes bone formation, a key macromolecule in the CS. Injection of pure M-CSF attenuated experimental periodontal alveolar bone loss in rats. Colony-stimulating factor 1 receptor (CSF1R) inhibitor or anti-human M-CSF (M-CSF neutralizing antibody, Nab) abolished the therapeutic effects of the CS of BBR-treated HBMSCs. Moreover, AKT phosphorylation in macrophages was activated by the CS, and the AKT activator reversed the negative effect of the CSF1R inhibitor or Nab. These results suggest that the CS of BBR-treated HBMSCs modulates macrophage polarization via the M-CSF/AKT axis. Further studies also showed that CS of BBR-treated HBMSCs accelerated bone formation and M2 polarization in rat teeth extraction sockets. Overall, our findings established an essential role of BBR-treated HBMSCs CS and this might be the first report to show that the products of BBR-treated HBMSCs have active effects on alveolar bone regeneration.


Assuntos
Perda do Osso Alveolar , Berberina , Regeneração Óssea , Fator Estimulador de Colônias de Macrófagos , Macrófagos , Células-Tronco Mesenquimais , Berberina/farmacologia , Humanos , Animais , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Regeneração Óssea/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Ratos , Fator Estimulador de Colônias de Macrófagos/metabolismo , Perda do Osso Alveolar/metabolismo , Masculino , Ratos Sprague-Dawley , Osteogênese/efeitos dos fármacos , Células Cultivadas , Proteínas Proto-Oncogênicas c-akt/metabolismo , Camundongos
2.
Zhongguo Zhong Yao Za Zhi ; 48(16): 4467-4474, 2023 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-37802873

RESUMO

This study aimed to investigate the relationship between the promoting effect of Zuogui Pills on ovarian and vaginal angiogenesis in early-aging rats and mobilization factors granulocyte-macrophage colony-stimulating factor(GM-CSF), stromal cell-derived factor-1(SDF-1), and their receptors of endothelial progenitor cells(EPCs) and explore the mechanism of Zuogui Pills in improving reproductive hypofunction in early-aging rats. Ultra-high performance liquid chromatography-tandem mass spectrometry(UHPLC-MS/MS) was used to analyze the chemical components of the extract of Zuogui Pills. Forty 14-month-old female early-aging rats with estrous cycle disorder were randomly divided into a blank group, a conjugated estrogen group(conjugated estrogen suspension, 65 µg·kg~(-1)), and low-(11 g·kg~(-1)) and high-dose(33 g·kg~(-1)) Zuogui Pills groups, with 10 rats in each group. In addition, 10 4-month-old female rats were assigned to the youth control group. The rats in the blank group and the youth control group were treated with 20 g·kg~(-1) distilled water by gavage, while those in the groups with drug intervention were treated with corresponding drugs by gavage, once a day for 15 days. Enzyme-linked immunosorbent assay(ELISA) was used to detect the levels of SDF-1 and GM-CSF in the mobilization of EPCs in serum. Hematoxylin-eosin(HE) staining was used to observe the changes in the number of ovarian follicles at all levels and corpus luteum, the number of vaginal epithelial layers, the number of vaginal folds, and the blood vessels of ovarian and vaginal tissues in the groups with drug intervention. Western blot was used to detect the expression of ER, GM-CSFR, CXCR4, and CXCR7 proteins in ovarian and vaginal tissues. As revealed by the results, the blank group showed decreased number of corpus luteum, gro-wing follicles at all levels, and blood vessels(P<0.05), decreased thickness of vaginal mucosa, the number of epithelial layers, the number of vaginal folds, and the number of vessels in the lamina propria(P<0.05), reduced content of SDF-1 and GM-CSF in the peripheral blood(P<0.05), and down-regulated levels of ER, CXCR4, CXCR7, and GM-CSFR proteins in ovarian and vaginal tissues(P<0.05). The groups with drug intervention showed increased number of growing follicles at all levels, corpus luteum, and blood vessels(P<0.05), decreased number of atresia follicles(P<0.05), increased thickness of vaginal mucosa, the number of epithelial layers, the number of vaginal mucosal folds, and the number of blood vessels in the lamina propria(P<0.05), increased content of SDF-1 and GM-CSF in the peripheral blood(P<0.05), and up-regulated levels of ER, CXCR4, CXCR7, and GM-CSFR proteins in ovarian and vaginal tissues(P<0.05). This experiment suggests that Zuogui Pills may promote ovarian and vaginal angiogenesis and improve the reproductive function of early-aging rats by up-regulating the levels of mobilization factors SDF-1, GM-CSF, and their receptors of EPCs.


Assuntos
Estrogênios Conjugados (USP) , Fator Estimulador de Colônias de Granulócitos e Macrófagos , Ratos , Feminino , Animais , Espectrometria de Massas em Tandem , Envelhecimento , Genitália
3.
Artigo em Chinês | WPRIM | ID: wpr-973235

RESUMO

ObjectiveTo investigate whether there exists gender differences in mechanical pain hypersensitivity induced by the subcutaneous injection of macrophage colony-stimulating factor (M-CSF) in normal mice and to explore the preliminary mechanism. MethodsThirty 10-week-old C57BL/6J mice were randomly divided into three groups, (n = 10 mice/group, half male and half female). The albumin control group (BSA, 0.3 μg), low dose M-CSF group (L M-CSF, 0.075 μg) and high dose M-CSF group (H M-CSF, 0.3 μg) received 50 μL BSA or M-CSF injected subcutaneously into the left medial thigh once daily for 3 consecutive days. Before and after drug administration, von-Frey mechanical sensitivity test was used to detect the mechanical paw withdrawal threshold (PWT) in each group. Immunofluorescence was performed to examine the expression changes of Ionized calcium-binding adaptor molecule 1 (Iba1) in skin, calcitonin gene-related peptide (CGRP) and phosphorylated ERK1/2 (p-ERK) in L5-L6 DRG and lumbar spinal dorsal horn. ResultsIn female mice, only high dose of M-CSF caused mechanical allodynia, whereas in male mice both doses produced marked allodynia. Mechanically, high-dose M-CSF induced massive aggregation of subcutaneous macrophages (marked by Iba1) in male and female mice, but more dramatic dependence in female mice. Similar gender differences were also found in the increase of p-ERK and CGRP expression in dorsal root ganglion (DRGs). Notably, CGRP expression was especially elevated in the fibers of DRG in male mice. Correspondingly, the expressions of p-ERK and CGRP+ terminals in the superficial spinal dorsal horn of male mice were significantly higher than those of female mice after M-CSF treatment. ConclusionSubcutaneous injection of M-CSF triggers sexual dimorphism in mechanical pain hypersensitivity, which is related with differential changes in peripheral macrophage expansion and sensitization of the nociceptive pathway.

4.
Brain Behav Immun Health ; 22: 100468, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35571146

RESUMO

Objective: Mechanisms driving temporal fluctuations of inflammatory markers during pregnancy, and how these might differ between distinct perinatal depressive trajectories, are not well understood. The aim of this study was to investigate cytokines levels over the course of pregnancy in women with different trajectories of depressive symptoms peripartum, and relate the levels to levels of non-pregnant controls. Methods: Based on the Edinburgh Postnatal Depression Scale and/or selective serotonin reuptake inhibitors use, 131 women were categorized into: no (n = 65); antepartum (APD, n = 19), postpartum (PPD, n = 17) and persistent (n = 30) depressive symptoms. Plasma samples (n = 386) were analyzed for levels of interleukin (IL)-8, IL-18, Tumor necrosis factor-α, macrophage colony-stimulating factor (M-CSF), vascular endothelial growth factor A (VEGF-A) and fractalkine, at four different time-points (twice during pregnancy, during childbirth, and postpartum) using Bio-Plex Pro Human Cytokine Assays. Generalized linear mixed models were applied to analyze the associations between cytokine levels, time-point, perinatal depressive symptom trajectory group and their interaction. Results: For all markers but VEGF-A, pregnancy was associated with higher cytokine levels compared to the non-pregnant controls, with delivery being the most prominent time-point. For M-CSF, IL-18 and VEGF-A, levels were back to the non-pregnant status at postpartum week 8. An effect of perinatal depressive symptom trajectory groups on cytokine levels was found for VEGF-A. Women with PPD and women with APD had lower levels of VEGF-A throughout the study period compared to women with persistent depression, and women with PPD had lower levels compared to non-depressed women. Conclusions: Lower levels of VEGF-A were noted among women in some trajectories of depressive symptoms peripartum. The peripartum period is a time of tremendous immune system adaptations. Standardization of time-points for cytokine measurements in studies of perinatal depression are important in order to draw valid conclusions on the role of the immune system in perinatal depression.

5.
Cell Rep ; 39(3): 110719, 2022 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-35443173

RESUMO

Metabolic adaptations can directly influence the scope and scale of macrophage activation and polarization. Here we explore the impact of type I interferon (IFNß) on macrophage metabolism and its broader impact on cytokine signaling pathways. We find that IFNß simultaneously increased the expression of immune-responsive gene 1 and itaconate production while inhibiting isocitrate dehydrogenase activity and restricting α-ketoglutarate accumulation. IFNß also increased the flux of glutamine-derived carbon into the tricarboxylic acid cycle to boost succinate levels. Combined, we identify that IFNß controls the cellular α-ketoglutarate/succinate ratio. We show that by lowering the α-ketoglutarate/succinate ratio, IFNß potently blocks the JMJD3-IRF4-dependent pathway in GM-CSF and IL-4 activated macrophages. The suppressive effects of IFNß on JMJD3-IRF4-dependent responses, including M2 polarization and GM-CSF-induced inflammatory pain, were reversed by supplementation with α-ketoglutarate. These results reveal that IFNß modulates macrophage activation and polarization through control of the cellular α-ketoglutarate/succinate ratio.


Assuntos
Interferon Tipo I , Ativação de Macrófagos , Fator Estimulador de Colônias de Granulócitos e Macrófagos/genética , Ácidos Cetoglutáricos/metabolismo , Ácidos Cetoglutáricos/farmacologia , Ácido Succínico
6.
J Ginseng Res ; 45(6): 617-630, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34764717

RESUMO

Chemotherapy-induced side effects affect the quality of life and efficacy of treatment of cancer patients. Current approaches for treating the side effects of chemotherapy are poorly effective and may cause numerous harmful side effects. Therefore, developing new and effective drugs derived from natural non-toxic compounds for the treatment of chemotherapy-induced side effects is necessary. Experiments in vivo and in vitro indicate that Panax ginseng (PG) and its ginsenosides are undoubtedly non-toxic and effective options for the treatment of chemotherapy-induced side effects, such as nephrotoxicity, hepatotoxicity, cardiotoxicity, immunotoxicity, and hematopoietic inhibition. The mechanism focus on anti-oxidation, anti-inflammation, and anti-apoptosis, as well as the modulation of signaling pathways, such as nuclear factor erythroid-2 related factor 2 (Nrf2)/heme oxygenase-1 (HO-1), P62/keap1/Nrf2, c-jun N-terminal kinase (JNK)/P53/caspase 3, mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinases (ERK), AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR), mitogen-activated protein kinase kinase 4 (MKK4)/JNK, and phosphatidylinositol 3-kinase (PI3K)/AKT. Since a systemic review of the effect and mechanism of PG and its ginsenosides on chemotherapy-induced side effects has not yet been published, we provide a comprehensive summarization with this aim and shed light on the future research of PG.

7.
Metabol Open ; 11: 100115, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34341776

RESUMO

COVID-19 is the respiratory illness caused by the novel coronavirus, SARS-CoV-2. Cytokine storm appears to be a factor in COVID-19 mortality. Echinacea species have been used historically for immune modulation. A previous rapid review suggested that Echinacea supplementation may decrease the levels of pro-inflammatory cytokines involved in cytokine storm. The objective of the present systematic review was to identify all research that has assessed changes in levels of cytokines relevant to cytokine storm in response to administration of Echinacea supplementation. The following databases were searched: Medline (Ovid), AMED (Ovid), CINAHL (EBSCO), EMBASE (Ovid). Title and abstract screening, full text screening, and data extraction were completed in duplicate using a piloted extraction template. Risk of bias assessment was completed. Qualitative analysis was used to assess for trends in cytokine level changes. The search identified 279 unique publications. After full text screening, 105 studies met criteria for inclusion including 13 human studies, 24 animal studies, and 71 in vitro or ex vivo studies. The data suggest that Echinacea supplementation may be associated with a decrease in the pro-inflammatory cytokines IL-6, IL-8, and TNF, as well as an increase in the anti-inflammatory cytokine IL-10. The risk of bias in the included studies was generally high. While there is currently no substantive research on the therapeutic effects of Echinacea in the management of either cytokine storm or COVID-19, the present evidence related to the herb's impact on cytokine levels suggests that further research may be warranted in the form of a clinical trial involving patients with COVID-19.

8.
J Ginseng Res ; 44(1): 8-13, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32095092

RESUMO

Atopic dermatitis (AD) is a chronic and relapsing inflammatory disease that affects 1%-20% of people worldwide. Despite affecting many people, AD current treatments, such as corticosteroids and calcineurin inhibitors, have not only harmful secondary effects but are also often ineffective. Therefore, natural nontoxic compounds are on high demand for developing new effective AD treatments. Panax ginseng Meyer has been used traditionally for its promising healing and restorative properties to treat many diseases including skin disorders, reason why in this review we want to explore the research performed with AD and P. ginseng as well as determining its potential for new drug development. Previous researches have shown that P. ginseng has positive effects in AD patients such as lower eczema area and severity index, transepidermal water loss, and immunoglobulin E levels and better quality of sleep. In vivo animal models, as well, have shown positive results to P. ginseng and derived ginsenosides, such as the decrease of transepidermal water loss, immunoglobulin E levels in serum, allergy-related cytokines, and downregulation of NF-κB, MAPK, and Ikaros pathways. All of these previous data suggest that P. ginseng and its derived ginsenosides are undoubtedly a nontoxic effective option to treat AD.

9.
Regen Ther ; 15: 216-225, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33426222

RESUMO

INTRODUCTION: Responses of oral-microflora-exposed dental pulp to a triple antibiotic paste (TAP), a mixture of ciprofloxacin, metronidazole, and minocycline in ointment with macrogol and propylene glycol, remain to be fully clarified at the cellular level. This study aimed to elucidate responses of oral-microflora-exposed dental pulp to capping with TAP in mouse molars. METHODS: A cavity was prepared on the first molars of 6-week-old mice to expose the dental pulp for 24 h. The exposed pulp was capped with TAP (TAP group) or calcium hydroxide cement (CH group), in addition to the combination of macrogol (M) and propylene glycol (P) (MP, control group), followed by a glass ionomer cement filling. The samples were collected at intervals of 1, 2, and 3 weeks, and immunohistochemistry for nestin and Ki-67 and deoxyuride-5'-triphosphate biotin nick end labeling (TUNEL) assay were performed in addition to quantitative real-time polymerase chain reaction (qRT-PCR) analyses. RESULTS: The highest occurrence rate of pulp necrosis was found in the control group followed by the CH group at Weeks 2 and 3, whereas the highest occurrence rate of healed areas in the dental pulp was observed in the TAP group at each time point. Tertiary dentin formation was first observed in the dental pulp of the TAP group at Week 2. In contrast, bone-like and/or fibrous tissues were frequently observed in the CH group. qRT-PCR analyses clarified that TAP activated the stem and dendritic cells at Weeks 1 and 2, respectively. CONCLUSIONS: The use of TAP as a pulp-capping agent improved the healing process of oral-microflora-exposed dental pulp in mouse molars.

10.
J Food Biochem ; 44(1): e13083, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31633209

RESUMO

Pithecellobium dulce (Family: Fabaceae) is an edible fruit widely used in Asian-Pacific region. In the present study, we had investigated the protective effect of P. dulce fruit extract in mitigating harmful effects of the chemotherapeutic drug, cyclophosphamide (CTX). Our results showed that P. dulce treatment could significantly (p < .01) overcome CTX-induced immunosuppression accompanied with urotoxicity, hepatotoxicity, and nephrotoxicity in experimental animals. This was supported by histopathological data which proved that toxic effects of CTX in urinary bladder walls, liver, and kidney were markedly inhibited with P. dulce administration. Further, we observed significant alterations in in situ formation or release of granulocyte-macrophage colony-stimulation factor (GM-CSF) and interferon gamma (IFN ɤ) in the P. dulce treated group compared with cyclophosphamide control group. The outcome of the study could have wide range of applications in combating chemotherapy-associated malnutrition as well as in cancer drug development. PRACTICAL APPLICATIONS: CTX is a commonly used broad spectrum chemotherapeutic drug with severe side effects including immune suppression, malnutrition, urotoxicity, and nephrotoxicity. Identification of a novel immunomodulator from natural sources can resolve these side effects and could improve the quality of life of cancer patients receiving CTX as chemotherapeutic drug. In the present study, we had proved that P. dulce administration could significantly reduce CTX-induced immunotoxicity, urothelial toxicity, and nephrotoxicity. Administration of P. dulce showed a pronounced improvement in total leukocyte count, bone marrow cellularity/α-esterase activity, expression of antioxidant glutathione and cytokines (GM-CSF and INF-ɤ) compared to CTX-treated mice group. Further, histopathological analysis confirmed the protective efficacy of P. dulce against CTX-induced urothelial, hepato and kidney damage. These insights are fostering new combinational therapeutic approaches to cancer treatment.


Assuntos
Citocinas , Fabaceae , Animais , Ciclofosfamida/toxicidade , Frutas , Humanos , Camundongos , Extratos Vegetais/farmacologia , Qualidade de Vida
11.
J Tradit Complement Med ; 9(3): 227-235, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31193882

RESUMO

OBJECTIVE: To investigate the development of a minimal traditional Chinese medicine (TCM) formula using selected TCM ingredients and evaluating their biological activity with bone-specific in vitro tests. Finally, determining if the minimal formula can maintain bone mineral density (BMD) in a low bone mass (LBM)/osteoporosis (OP) model system. METHODS AND RESULTS: Sixteen different TCM plant extracts were tested for estrogenic, osteogenic and osteoclastic activities. Despite robust activation of the full-length estrogen receptors α and ß by Psoralea corylifolia and Epimedium brevicornu, these extracts do not activate the isolated estrogen ligand binding domains (LBD) of either ERα or ERß; estrogen (17-ß estradiol) fully activates the LBD of ERα and ERß. E. brevicornu and Drynaria fortunei extracts activated cyclic AMP response elements (CRE) individually and when combined these ingredients stimulated the production of osteoblastic markers Runx2 and Bmp4 in MC3T3-E1 cells. E. brevicornu, Salvia miltiorrhiza, and Astragalus onobrychis extracts inhibited the Il-1ß mediated activation of NF-κß and an E. brevicornu/D. fortunei combination inhibited the development of osteoclasts from precursor cells. Further, a minimal formula containing the E. brevicornu/D. fortunei combination with or without a third ingredient (S. miltiorrhiza, Angelica sinensis, or Lycium barbarum) maintained bone mineral density (BMD) similar to an estradiol-treated control group in the ovariectomized rat; a model LBM/OP system. CONCLUSION: A minimal formula consisting of TCM plant extracts that activate CRE and inhibit of NF-κß activation, but do not behave like estrogen, maintain BMD in a LBM/OP model system.

12.
J Bone Oncol ; 15: 004-4, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30937279

RESUMO

Bone metastases (BM) are a common complication of cancer, whose management often requires a multidisciplinary approach. Despite the recent therapeutic advances, patients with BM may still experience skeletal-related events and symptomatic skeletal events, with detrimental impact on quality of life and survival. A deeper knowledge of the mechanisms underlying the onset of lytic and sclerotic BM has been acquired in the last decades, leading to the development of bone-targeting agents (BTA), mainly represented by anti-resorptive drugs and bone-seeking radiopharmaceuticals. Recent pre-clinical and clinical studies have showed promising effects of novel agents, whose safety and efficacy need to be confirmed by prospective clinical trials. Among BTA, adjuvant bisphosphonates have also been shown to reduce the risk of BM in selected breast cancer patients, but failed to reduce the incidence of BM from lung and prostate cancer. Moreover, adjuvant denosumab did not improve BM free survival in patients with breast cancer, suggesting the need for further investigation to clarify BTA role in early-stage malignancies. The aim of this review is to describe BM pathogenesis and current treatment options in different clinical settings, as well as to explore the mechanism of action of novel potential therapeutic agents for which further investigation is needed.

13.
J Am Acad Dermatol ; 81(2): 558-567, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30802561

RESUMO

Radiation dermatitis is a common sequela of radiation therapy; up to 95% of patients will develop moderate-to-severe skin reactions. No criterion standard currently exists for the treatment of acute radiation-induced skin toxicity. It is therefore imperative to develop a greater understanding of management options available to allow clinicians to make informed decisions when managing radiation oncology patients. This literature review discusses the topical agents that have been studied for the treatment of acute radiation dermatitis, reviews their mechanisms of action, and presents a treatment algorithm for clinicians managing patients experiencing radiation dermatitis.


Assuntos
Algoritmos , Fármacos Dermatológicos/uso terapêutico , Radiodermite/tratamento farmacológico , Doença Aguda , Corticosteroides/uso terapêutico , Anti-Infecciosos Locais/uso terapêutico , Bandagens , Produtos Biológicos/uso terapêutico , Etanolaminas/uso terapêutico , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Preparações de Plantas/uso terapêutico , Radiodermite/etiologia , Radioterapia/efeitos adversos , Sulfadiazina de Prata/uso terapêutico , Sucralfato/uso terapêutico , Vitaminas/uso terapêutico
14.
Br J Nutr ; 120(12): 1321-1331, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30375295

RESUMO

Ca2+-sensing receptor (CaSR) represents a potential therapeutic target for inflammatory bowel diseases and strongly prefers aromatic amino acid ligands. We investigated the regulatory effects of dietary supplementation with aromatic amino acids - tryptophan, phenylalanine and tyrosine (TPT) - on the CaSR signalling pathway and intestinal inflammatory response. The in vivo study was conducted with weanling piglets using a 2 × 2 factorial arrangement in a randomised complete block design. Piglets were fed a basal diet or a basal diet supplemented with TPT and with or without inflammatory challenge. The in vitro study was performed in porcine intestinal epithelial cell line to investigate the effects of TPT on inflammatory response using NPS-2143 to inhibit CaSR. Dietary supplementation of TPT alleviated histopathological injury and decreased myeloperoxidase activity in intestine challenged with lipopolysaccharide. Dietary supplementation of TPT decreased serum concentration of pro-inflammatory cytokines (IL-1ß, IL-6, IL-8, IL-12, granulocyte-macrophage colony-stimulating factor, TNF-α), as well as the mRNA abundances of pro-inflammatory cytokines in intestine but enhanced anti-inflammatory cytokines IL-4 and transforming growth factor-ß mRNA levels compared with pigs fed control diet and infected by lipopolysaccharide. Supplementation of TPT increased CaSR and phospholipase Cß2 protein levels, but decreased inhibitor of NF-κB kinase α/ß and inhibitor of NF-κB (IκB) protein levels in the lipopolysaccharide-challenged piglets. When the CaSR signalling pathway was blocked by NPS-2143, supplementation of TPT decreased the CaSR protein level, but enhanced phosphorylated NF-κB and IκB levels in IPEC-J2 cells. To conclude, supplementation of aromatic amino acids alleviated intestinal inflammation as mediated through the CaSR signalling pathway.


Assuntos
Aminoácidos Aromáticos/administração & dosagem , Inflamação/metabolismo , Intestinos/patologia , Receptores de Detecção de Cálcio/metabolismo , Animais , Colo/metabolismo , Citocinas/sangue , Dieta , Suplementos Nutricionais , Células Epiteliais/metabolismo , Feminino , Quinase I-kappa B/metabolismo , Jejuno/metabolismo , Lipopolissacarídeos , NF-kappa B/metabolismo , Peroxidase/metabolismo , Fenilalanina/administração & dosagem , Fosforilação , RNA Mensageiro/metabolismo , Distribuição Aleatória , Transdução de Sinais , Sus scrofa , Suínos , Triptofano/administração & dosagem , Fator de Necrose Tumoral alfa/metabolismo , Tirosina/administração & dosagem
15.
Mol Med Rep ; 17(3): 4067-4073, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29257323

RESUMO

Oxyresveratrol and its glycoside are important natural active materials. As an effective tyrosine kinase inhibitor, oxyresveratrol may prevent herpes virus infection, inflammation and oxidative stress, as well as protect nerves. In addition, it is known to inhibit cell apoptosis following cerebral ischemia. In recent years, oxyresveratrol and its glycoside have been widely investigated, and their useful biological activities have been explored, indicating that they may be worthy of further comprehensive research. The aim of the present study was to evaluate the photoprotective effects of oxyresveratrol and its ability to abrogate inflammation and oxidative stress in a rat model of spinal cord injury (SCI). The authors identified that oxyresveratrol significantly reversed the SCI­induced inhibition of Basso, Beattie, and Bresnahan scores, inhibited the SCI­mediated increase in spinal cord water content, significantly suppressed SCI­induced nuclear factor­κB/p65, tumor necrosis factor­α, interleukin (IL)­1ß and IL­6 activities and reversed the malondialdehyde, superoxide dismutase, glutathione (GSH) and GSH peroxidase activities in SCI rats. SCI­induced granulocyte­macrophage colony­stimulating factor (GM­CSF), inducible nitric oxide synthase (iNOS) and cyclo­oxygenase­2 (COX­2) protein expression was significantly suppressed by oxyresveratrol, and SCI­mediated inhibition of nuclear factor (erythroid­derived 2)­like 2 (Nrf2) protein expression was significantly increased by oxyresveratrol. In conclusion, these results suggest that the effects of oxyresveratrol restores SCI, and abrogates inflammation and oxidative stress in rat model of SCI via the GM­CSF, iNOS, COX­2 and Nrf2 signaling pathway.


Assuntos
Antioxidantes/farmacologia , Locomoção/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Extratos Vegetais/farmacologia , Traumatismos da Medula Espinal/tratamento farmacológico , Medula Espinal/efeitos dos fármacos , Estilbenos/farmacologia , Animais , Modelos Animais de Doenças , Esquema de Medicação , Feminino , Regulação da Expressão Gênica , Glutationa Peroxidase/genética , Glutationa Peroxidase/metabolismo , Fator Estimulador de Colônias de Granulócitos e Macrófagos/genética , Fator Estimulador de Colônias de Granulócitos e Macrófagos/metabolismo , Inflamação , Injeções Intraperitoneais , Interleucina-1beta/antagonistas & inibidores , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Interleucina-6/antagonistas & inibidores , Interleucina-6/genética , Interleucina-6/metabolismo , Malondialdeído/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Estresse Oxidativo , Ratos , Ratos Sprague-Dawley , Medula Espinal/metabolismo , Medula Espinal/patologia , Traumatismos da Medula Espinal/genética , Traumatismos da Medula Espinal/metabolismo , Traumatismos da Medula Espinal/patologia , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Fator de Transcrição RelA/antagonistas & inibidores , Fator de Transcrição RelA/genética , Fator de Transcrição RelA/metabolismo , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
16.
Biosci Biotechnol Biochem ; 82(4): 654-668, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29207919

RESUMO

Certain food components possess immunomodulatory effects. The aim of this study was to elucidate the mechanism of the immunostimulatory activity of Brassica rapa L. We demonstrated an enhancement of natural killer (NK) activity and interferon (IFN)-γ production in mice that were orally administered an insoluble fraction of B. rapa L. The insoluble fraction of B. rapa L. significantly induced IFN-γ production in mouse spleen cells in an interleukin (IL)-12-dependent manner, and NK1.1+ cells were the main cells responsible for producing IFN-γ. Additionally, the results suggested that the active compounds in the insoluble fraction were recognized by Toll-like receptor (TLR) 2, TLR4, and C-type lectin receptors on dendritic cells, and they activated signaling cascades such as MAPK, NF-κB, and Syk. These findings suggest that B. rapa L. is a potentially promising immuno-improving material, and it might be useful for preventing immunological disorders such as infections and cancers by activating innate immunity.


Assuntos
Brassica rapa/metabolismo , Alimento Funcional , Interferon gama/biossíntese , Interleucina-12/fisiologia , Células Matadoras Naturais/efeitos dos fármacos , Extratos Vegetais/farmacologia , Adjuvantes Imunológicos/administração & dosagem , Adjuvantes Imunológicos/farmacologia , Administração Oral , Animais , Citocinas/metabolismo , Feminino , Células Matadoras Naturais/imunologia , Lectinas Tipo C/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Extratos Vegetais/administração & dosagem , Transdução de Sinais , Baço/efeitos dos fármacos , Baço/metabolismo , Quinase Syk/metabolismo , Receptor 2 Toll-Like/metabolismo , Receptor 4 Toll-Like/metabolismo
17.
Hum Exp Toxicol ; 34(8): 808-18, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25425548

RESUMO

Excessive inflammation is considered a critical factor in many human diseases. Oxyresveratrol(trans-2,3',4,5'-tetrahydroxystilbene), a natural hydroxystilbene, has been shown to possess antioxidant and free radical-scavenging activity. In this study, we investigated the effects of oxyresveratrol (OxyR) on the lipopolysaccharide (LPS)-induced production of inflammatory cytokines and mediators and further explored the mechanism of action in RAW264.7 murine macrophage cell line. Production of nitric oxide (NO), prostaglandin E2 (PGE2), messenger RNA (mRNA) and protein expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin 6 (IL-6), and granulocyte macrophage colony-stimulating factor (GM-CSF), phosphorylation of mitogen-activated protein kinases (MAPKs; extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), p38), and the activation of nuclear factor κ-light chain enhancer of activated B cells (NFκB) with OxyR were assayed in LPS-stimulated RAW264.7 cells. OxyR inhibited the productions of NO, PGE2, IL-6, and GM-CSF significantly in LPS-stimulated RAW264.7 cells. OxyR suppressed mRNA and protein expressions of iNOS, COX-2, IL-6, and GM-CSF in LPS-stimulated RAW264.7 cells. OxyR suppressed the phosphorylation of Akt and JNK and p38 MAPKs and the translocation of NFκB p65 subunit into the nucleus. These results indicate that OxyR inhibits LPS-stimulated inflammatory responses though the blocking of MAPK and NFκB signaling pathway in macrophages, and suggest that OxyR possesses anti-inflammatory effects.


Assuntos
Inflamação/prevenção & controle , Lipopolissacarídeos/toxicidade , Macrófagos/efeitos dos fármacos , Extratos Vegetais/farmacologia , Estilbenos/farmacologia , Animais , Linhagem Celular , Ciclo-Oxigenase 2/metabolismo , Dinoprostona/biossíntese , Fator Estimulador de Colônias de Granulócitos e Macrófagos/biossíntese , Interleucina-6/biossíntese , Macrófagos/enzimologia , Macrófagos/imunologia , Camundongos , Óxido Nítrico/biossíntese , Óxido Nítrico Sintase Tipo II/metabolismo , Fosforilação , Proteínas Quinases/metabolismo
18.
Hum Vaccin Immunother ; 10(9): 2733-40, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25483491

RESUMO

Signal peptide (SP) domains have a common motif but also sequence specific features. This knowledge was mainly ignored by immunologists who considered SP as generic, short-lived, targeting sequences. Consequently, while SP-derived MHC class I, class II and HLA-E epitopes have been isolated, their use as antigen-specific vaccine candidates (VCs) was mostly neglected. Recently we demonstrated the rational of selecting entire SP domains as multi-epitope long peptide VCs based on their high T and B-cell epitope densities. This review summarizes preclinical and clinical results demonstrating the various advantages of human SP domain VCs derived from both bacterial and tumor antigens. Such vaccine design provides for a straightforward, yet unique immunotherapeutic means of generating robust, non-toxic, diversified, combined antigen-specific CD4+/CD8+ T/B-cell immunity, irrespective of patient HLA repertoire also in disease associated transporter-associated with antigen processing (TAP) deficiencies. Subsequent clinical trials will further assess the full potential of this approach.


Assuntos
Vacinas Bacterianas/imunologia , Vacinas Anticâncer/imunologia , Sinais Direcionadores de Proteínas , Vacinação/métodos , Linfócitos B/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Ensaios Clínicos como Assunto , Avaliação Pré-Clínica de Medicamentos , Epitopos/imunologia , Humanos
19.
Pharmacogn Mag ; 10(Suppl 3): S506-11, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25298667

RESUMO

BACKGROUND: So-Cheong-Ryong-Tang (SCRT), herbal medicine, has been used for the control of respiratory disease in East Asian countries. However, its therapeutic mechanisms, especially an inhibitory effect on inflammatory cell infiltration and airway remodeling in allergic asthma are unclear. OBJECTIVE: The present study investigated the mechanism of antiasthmatic effects of SCRT in allergic asthma in mice. MATERIALS AND METHODS: We investigated the influence of SCRT on levels of interleukin-17 (IL-17), granulocyte/macrophage colony-stimulating factor (GM-CSF), IL-4, and interferon gamma (IFN-γ) in bronchoalveolar lavage fluid (BALF), ovalbumin (OVA)-specific IgE in serum, and histopathological changes in allergen-induced asthma. RESULTS: So-Cheong-Ryong-Tang decreased levels of IL-17 and GM-CSF in BALF. IL-4, a Th2-driven cytokine, was also decreased by SCRT, but IFN-γ, a Th1-driven cytokine, was not changed. Levels of OVA-specific IgE in serum were also decreased by SCRT. With SCRT treatment, histopathological findings showed reduced tendency of inflammatory cell infiltration, and prevention from airway remodeling such as epithelial hyperplasia. CONCLUSION: In this study, we firstly demonstrated that regulation of IL-17 and GM-CSF production may be one of the mechanism contributed to a reduction of inflammatory cell infiltration and prevention from airway remodeling.

20.
Gene ; 537(1): 29-40, 2014 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-24389500

RESUMO

Change in transcription start site (TSS) usage is an important mechanism for the control of transcription process, and has a significant effect on the isoforms being transcribed. One of the goals in the study of TSS is the understanding of how and why their usage differs in different tissues or under different conditions. In light of recent efforts in the mapping of transcription start site landscape using high-throughput sequencing approaches, a quantitative and automated method is needed to process all the data that are being produced. In this work we propose a statistical approach that will classify changes in TSS distribution between different samples into several categories of changes that may have biological significance. Genes selected by the classifiers can then be analyzed together with additional supporting data to determine their biological significance. We use a set of time-course TSS data from mouse dendritic cells stimulated with lipopolysaccharide (LPS) to demonstrate the usefulness of our method.


Assuntos
Regulação da Expressão Gênica , Imunidade Inata/genética , Receptores Toll-Like/metabolismo , Sítio de Iniciação de Transcrição , Animais , Interpretação Estatística de Dados , Bases de Dados Genéticas , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/fisiologia , Ontologia Genética , Humanos , Lipopolissacarídeos/farmacologia , Camundongos , Regiões Promotoras Genéticas , Proto-Oncogene Mas , Transdução de Sinais/genética , Receptores Toll-Like/genética
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