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1.
Cancer Genomics Proteomics ; 18(5): 675-684, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34479919

RESUMO

BACKGROUND: We propose a novel prognostic biomarker-based strategy for increasing the efficacy of radiotherapy (RT) in head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: We identified genes associated with superoxide dismutase 2 (SOD2) and nuclear factor erythroid-2-related factor 2 (NRF2) from gene-expression data of The Cancer Genome Atlas (TCGA) by calculating Pearson correlation. Patients were divided into two groups using hierarchical clustering. Colony-formation assay was performed to determine radioresistance in HNSCC cell line CAL27. Pathway analysis was conducted using The Database for Annotation, Visualization and Integrated Discovery (DAVID). RESULTS: We developed a 49-gene signature with SOD2- and NRF2-associated genes. Using mRNA expression data for the 49-gene signature, we performed hierarchical clustering to stratify patients into two subtypes, subtype A and B. In the TCGA cohort, subgroup A demonstrated a better prognosis than subgroup B in patients who received RT. The signature robustness was evaluated in other independent cohorts. We showed through colony-formation assay that depletion of SOD2 or NRF2 leads to increased radiosensitivity. CONCLUSION: We identified and validated a robust gene signature of SOD2- and NRF2-associated genes in HNSCC and confirmed their link to radioresistance using in vitro assay, providing a novel biomarker for the evaluation of HNSCC prognosis.

2.
Int J Mol Sci ; 22(16)2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34445514

RESUMO

Oxaliplatin, a well-known chemotherapeutic agent, can induce severe neuropathic pain, which can seriously decrease the quality of life of patients. JI017 is an herb mixture composed of Aconitum carmichaelii, Angelica gigas, and Zingiber officinale. Its anti-tumor effect has been reported; however, the efficacy of JI017 against oxaliplatin-induced allodynia has never been explored. Single oxaliplatin injection [6 mg/kg, intraperitoneal, (i.p.)] induced both cold and mechanical allodynia, and oral administration of JI017 (500 mg/kg) alleviated cold but not mechanical allodynia in mice. Real-time polymerase chain reaction (PCR) analysis demonstrated that the upregulation of mRNA of spinal transient receptor potential vanilloid 1 (TRPV1) and astrocytes following oxaliplatin injection was downregulated after JI017 treatment. Moreover, TRPV1 expression and the activation of astrocytes were intensely increased in the superficial area of the spinal dorsal horn after oxaliplatin treatment, whereas JI017 suppressed both. The administration of TRPV1 antagonist [capsazepine, intrathecal (i.t.), 10 µg] attenuated the activation of astrocytes in the dorsal horn, demonstrating that the functions of spinal TRPV1 and astrocytes are closely related in oxaliplatin-induced neuropathic pain. Altogether, these results suggest that JI017 may be a potent candidate for the management of oxaliplatin-induced neuropathy as it decreases pain, spinal TRPV1, and astrocyte activation.


Assuntos
Astrócitos/metabolismo , Hiperalgesia/tratamento farmacológico , Oxaliplatina/efeitos adversos , Compostos Fitoquímicos/administração & dosagem , Canais de Cátion TRPV/metabolismo , Aconitum/química , Administração Oral , Angelica/química , Animais , Astrócitos/efeitos dos fármacos , Temperatura Baixa , Modelos Animais de Doenças , Regulação para Baixo , Gengibre/química , Hiperalgesia/induzido quimicamente , Hiperalgesia/genética , Hiperalgesia/metabolismo , Camundongos , Compostos Fitoquímicos/farmacologia , Coluna Vertebral/metabolismo , Canais de Cátion TRPV/genética
3.
Int J Mol Sci ; 22(16)2021 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-34445110

RESUMO

Epidermal growth factor receptor (EGFR) is overexpressed in lung cancer patients. Despite treatment with various EGFR tyrosine kinase inhibitors, recurrence and metastasis of lung cancer are inevitable. Docetaxel (DTX) is an effective conventional drug that is used to treat various cancers. Several researchers have studied the use of traditional herbal medicine in combination with docetaxel, to improve lung cancer treatment. SH003, a novel herbal mixture, exerts anticancer effects in different cancer cell types. Here, we aimed to investigate the apoptotic and anticancer effects of SH003 in combination with DTX, in human non-small-cell lung cancer (NSCLC). SH003, with DTX, induced apoptotic cell death, with increased expression of cleaved caspases and cleaved poly (ADP-ribose) polymerase in NSCLC cells. Moreover, SH003 and DTX induced the apoptosis of H460 cells via the suppression of the EGFR and signal transducer and activator of transcription 3 (STAT3) signaling pathways. In H460 tumor xenograft models, the administration of SH003 or docetaxel alone diminished tumor growth, and their combination effectively killed cancer cells, with increased expression of apoptotic markers and decreased expression of p-EGFR and p-STAT3. Collectively, the combination of SH003 and DTX may be a novel anticancer strategy to overcome the challenges that are associated with conventional lung cancer therapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Docetaxel/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Extratos Vegetais/farmacologia , Transdução de Sinais/efeitos dos fármacos , Células A549 , Inibidores da Angiogênese/farmacologia , Animais , Apoptose/efeitos dos fármacos , Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Receptores ErbB/metabolismo , Humanos , Neoplasias Pulmonares/metabolismo , Camundongos , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Fator de Transcrição STAT3/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto/métodos
4.
Otolaryngol Head Neck Surg ; : 1945998211026843, 2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34253074

RESUMO

OBJECTIVE: This study aimed to evaluate the characteristics of reflux in proton pump inhibitor (PPI) nonresponders vs responders in patients with laryngopharyngeal reflux (LPR) by using 24-hour multichannel intraluminal impedance-pH (MII-pH) monitoring. STUDY DESIGN: Prospective cohort study. SETTING: A tertiary care otolaryngology clinic. METHODS: Patients with typical LPR symptoms showing >1 proximal reflux episode were considered to have LPR and investigated prospectively. Patients were prescribed high-dose PPI twice daily and followed up for at least 2 months. Patients with LPR showing a ≥50% decrease in the follow-up reflux symptom index score during treatment periods as compared with pretreatment were defined as responders; others were defined as nonresponders. Various parameters in 24-hour MII-pH monitoring between nonresponders and responders with LPR were compared with Student's t test and receiver operating characteristic curve. RESULTS: Eighty patients were diagnosed with LPR and categorized as nonresponders (n = 19) and responders (n = 61). Proximal all reflux time and proximal longest reflux time in various MII parameters were higher in responders than in nonresponders (P = .0040 and .0216, respectively). Proximal all reflux time >0.000517% was a better cutoff value to predict responders with LPR as compared with the proximal longest reflux time >0.61 minutes (sensitivity + specificity: 1.317 vs 1.291). CONCLUSION: Proximal all reflux time in various 24-hour MII-pH monitoring parameters can be helpful to predict the response to PPI therapy in patients with LPR. These findings will help establish a personalized therapeutic scheme for patients with LPR.

5.
Biomed Pharmacother ; 141: 111835, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34146852

RESUMO

Thymic stromal lymphopoietin (TSLP) produced by mast cells is involved in allergic inflammation pathogenesis. Chloroquine (CQ) is known to be an anti-malarial drug; however, additional protective functions of CQ have been discovered. This study aims to clarify an anti-inflammatory effect of CQ through modulating TSLP levels using an in vitro model of phorbol myristate acetate (PMA) + A23187-activated human mast cell line (HMC-1) and an in vivo model of PMA-irritated ear edema. CQ treatment reduced the production and mRNA expression levels of TSLP in activated HMC-1 cells. CQ down-regulated caspase-1 (CASP1), MAPKs, and NF-κB levels enhanced by stimulation with PMA + A23187. Moreover, ear thickness in ear edema was suppressed following CQ treatment. CQ decreased CASP1 and NF-κB levels in the ear tissue. TSLP levels in the ear tissue and serum were reduced following CQ treatment. Collectively, the above findings elucidate that CQ inhibits the pro-inflammatory mechanisms of TSLP via the down-regulation of distinct intracellular signaling cascade in mast cells. Therefore, CQ may have protective roles against TSLP-mediated inflammatory disorders.

6.
Mol Oncol ; 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33931944

RESUMO

Targeting autophagy is a promising therapeutic approach in cancer therapy. Here, we screened 30 traditional herbal medicines to identify novel autophagy regulators and found that Platycodon grandiflorus (PG) and platycodin D (PD), a triterpenoid saponin from PG, inhibited autophagy in glioblastoma multiforme (GBM) cells. Mechanistically, PD prevented lysosomal degradation and the fusion between autophagosomes and lysosomes by inducing sequestration of free cholesterol in lysosomes. The autophagy inhibitory effect of PD was mimicked by both genetic and pharmacological inhibition of Niemann-Pick C1 (NPC1), which exports low-density lipoprotein (LDL)-derived cholesterol from lysosomes. Moreover, PD promoted the uptake of exogenous LDL cholesterol via upregulation of LDL receptor (LDLR), leading to further accumulation of cholesterol within lysosomes and GBM cell death. Importantly, these phenomena were more pronounced in LDLR-overexpressing GBM cells than in normal astrocytes. Finally, blockade of cholesterol uptake by LDLR knockdown reversed the PD-induced inhibition of autophagy and GBM cell growth. Our study proposes that PD could be a potent anti-GBM drug by disrupting cholesterol trafficking and autophagy.

7.
Eur Arch Otorhinolaryngol ; 278(9): 3387-3392, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34036423

RESUMO

PURPOSE: This study aimed to analyze pharyngeal reflux episodes in patients with suspected LPR versus healthy subjects using 24-h MII-pH monitoring. METHODS: One hundred twenty-one patients who visited our clinic with a chief complaint of LPR-related symptoms and underwent 24-h MII-pH monitoring were enrolled prospectively. Also, 27 healthy subjects were enrolled and underwent 24-h MII-pH monitoring during the same period. We analyzed sensitivity, specificity, and accuracy comprehensively to determine appropriate cut-off values of pharyngeal reflux episodes in 24-h MII-pH monitoring to diagnose patients with LPR. RESULTS: Twenty-nine of 121 patients with suspected LPR showed no pharyngeal reflux episodes, while 92 showed more than one pharyngeal reflux event. In contrast, the 22 healthy subjects showed no pharyngeal reflux episodes, three showed one reflux event, and two showed two reflux events. A cut-off value of ≥ 1 showed best accuracy reflected by combined sensitivity and specificity values, while ≥ 2 demonstrated better specificity with slight loss of sensitivity and slightly lower overall accuracy, suggesting cut-off value of ≥ 1 pharyngeal reflux episodes is a good clinical indicator. CONCLUSION: A cut-off value of ≥ 1 in pharyngeal reflux episodes on 24-h MII-pH monitoring in patients with suspected LPR might be an acceptable diagnostic tool for LPR.


Assuntos
Refluxo Laringofaríngeo , Impedância Elétrica , Monitoramento do pH Esofágico , Voluntários Saudáveis , Humanos , Concentração de Íons de Hidrogênio , Refluxo Laringofaríngeo/complicações , Refluxo Laringofaríngeo/diagnóstico , Estudos Prospectivos
8.
Nutrients ; 13(3)2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33809267

RESUMO

Although the anti-obesity effect of Korean red ginseng (Panax ginseng Meyer) has been revealed, its underlying mechanisms are not clearly understood. Here, we demonstrate an involvement of gut microbiome in the inhibitory effect of Korean red ginseng on high-fat-diet (HFD)-induced mouse obesity, and further provides information on the effects of saponin-containing red ginseng extract (SGE) and saponin-depleted red ginseng extract (GE). Mice were fed with either SGE or GE every third day for one month, and their food intakes, fat weights, plasma glucose, and insulin and leptin levels were measured. Immunofluorescence assays were conducted to measure pancreatic islet size. Stools from the mice were subjected to metagenomic analysis. Both SGE and GE attenuated HFD-induced gain of body weight, reducing HFD-induced increase of food intakes and fat weights. They also reduced HFD-increased plasma glucose, insulin, and leptin levels, decreased both fasting and postprandial glucose concentrations, and improved both insulin resistance and glucose intolerance. Immunofluorescence assays revealed that they blocked HFD-induced increase of pancreatic islet size. Our pyrosequencing of the 16S rRNA gene V3 region from stools revealed that both SGE and GE modulated HFD-altered composition of gut microbiota. Therefore, we conclude that Korean red ginseng inhibits HFD-induced obesity and diabetes by altering gut microbiome.


Assuntos
Dieta Hiperlipídica/efeitos adversos , Microbioma Gastrointestinal , Obesidade/tratamento farmacológico , Panax , Fitoterapia/métodos , Extratos Vegetais/uso terapêutico , Animais , Glicemia/análise , Imunofluorescência , Microbioma Gastrointestinal/genética , Microbioma Gastrointestinal/fisiologia , Insulina/sangue , Leptina/sangue , Masculino , Metagenômica , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/microbiologia , Obesidade/patologia , Pâncreas/patologia , RNA Ribossômico 16S/genética
9.
Am J Chin Med ; 49(4): 829-841, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33829965

RESUMO

Integrative medicine has become a vital component of patient care. It provides patient-centered care that is focused on prevention and overall well-being. As there has been a growing number of patients favoring a blend of conventional, complementary and alternative approaches, integrative medicine has exceeded beyond the evaluation of complementary therapies. However, it is noteworthy that there has been a dilemma of providing substantial evidence supporting the efficacy of some complementary and alternative therapies. This study's goals were to analyze publication trends, most productive journals, most productive funding agencies, most productive authors, most relevant keywords, and countries in the field of integrative medicine research. Additionally, science mapping included country collaboration analysis and thematic evolution analysis. The findings from this study showed a constant rise in annual growth of publications from 2000 to 2019; the United States was dominant in various analysis categories. In conclusion, a comprehensive review of the evolution of research of integrative medicine will help healthcare providers understand an overview of the present status while encouraging more evidence-based research for the betterment of integrative patient care.


Assuntos
Bibliometria , Pesquisa Biomédica/tendências , Medicina Baseada em Evidências , Medicina Integrativa , Medicina Tradicional Chinesa , Publicações Periódicas como Assunto/tendências , Autoria , Humanos
10.
Otolaryngol Head Neck Surg ; : 1945998211006929, 2021 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-33878990

RESUMO

OBJECTIVE: To evaluate differences between manual and automated analyses of 24-hour multichannel intraluminal impedance-pH monitoring for diagnosis of laryngopharyngeal reflux. STUDY DESIGN: Case series with planned data collection. SETTING: Academic center outpatient clinic. METHODS: The study group comprised 127 patients with symptoms suspicious of laryngopharyngeal reflux, who underwent 24-hour multichannel intraluminal impedance-pH monitoring. Automated and manual analyses were performed for each patient. The following parameters were compared between analyses: number of proximal reflux episodes, proximal exposure time, symptom index, and symptom association probability. RESULTS: The number of proximal reflux episodes detected by manual analysis was significantly lower than that detected by automated analysis, except in acid reflux cases. The false positive of automated analysis was 39.8%. In addition, the proximal exposure time for manual analysis was significantly lower than that for automated analysis, except in cases of acid reflux. Symptom index and symptom association probability values based on manual analysis were significantly lower than in automated analysis, except in heartburn cases. CONCLUSIONS: Automated analysis demonstrated a tendency of excessive reflux measurement when compared with manual analysis. It is necessary to increase the accuracy of laryngopharyngeal reflux diagnosis through manual analysis.

11.
Nutrients ; 13(4)2021 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-33919521

RESUMO

The intestinal microbiome is considered one of the key regulators of health. Accordingly, the severity of atopic dermatitis (AD) is mediated by the skin and intestinal microbiome environment. In this study, while evaluating the aggravation in AD symptoms by the antibiotics cocktail (ABX)-induced depletion of the intestinal microbiome, we sought to verify the effect of Gardenia jasminoides (GJ), a medicinal herb used for inflammatory diseases, on AD regarding its role on the intestinal microbiome. To verify the aggravation in AD symptoms induced by the depletion of the intestinal microbiome, we established a novel mouse model by administrating an ABX to create a microbiome-free environment in the intestine, and then applied 2,4-dinitrochlorobenzene (DNCB) to induce an AD-like skin inflammatory response. While ABX treatment aggravated AD-like symptoms, the 2-week administration of GJ improved these pathological changes. DNCB application upregulated immune cell count and serum cytokine expression, which were alleviated by GJ. Moreover, pathological alterations by antibiotics and DNCB, including histological damage of the intestine and the intestinal expression of IL-17, were recovered in GJ-treated mice. The beneficial effect of GJ was due to the restoration of the intestinal microbiome composition. Overall, we suggest GJ as a potential therapeutic agent for AD due to its regulation of the intestinal microbiome.


Assuntos
Dermatite Atópica/tratamento farmacológico , Gardenia , Microbioma Gastrointestinal/efeitos dos fármacos , Extratos Vegetais/farmacologia , Pele/microbiologia , Animais , Antibacterianos/efeitos adversos , Dermatite Atópica/induzido quimicamente , Dermatite Atópica/microbiologia , Dinitroclorobenzeno , Modelos Animais de Doenças , Masculino , Camundongos , Camundongos Endogâmicos BALB C
12.
Am J Chin Med ; 49(3): 767-784, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33657989

RESUMO

Gliomas are the mostly observed form of primary brain tumor, and glioblastoma multiforme (GBM) shows the highest incidence. The survival rate of GBM is fairly poor; thus, discovery of effective treatment options is required. Among several suggested targets for therapy, the Axl/IL-6/STAT3 signaling pathway has gained recent interest because of its important role within cancer microenvironment. Quercetin, a plant flavonoid, is well known for its anticancer action. However, the effect of quercetin on Axl has never been reported. Quercetin treatment significantly reduced cell viability in two GBM cell lines of U87MG and U373MG while keeping 85% of normal astrocytes alive. Further western blot assays suggested that quercetin induces apoptosis but does not affect Akt or mitogen-activated protein kinases, factors related to cell proliferation. Quercetin also decreased IL-6 release and phosphorylation of STAT3 in GBM cells. In addition, gene expression, protein expression, and half-life of synthesized Axl protein were all suppressed by quercetin. By applying shRNA for knockdown of Axl, we could confirm that the role of Axl was crucial in the apoptotic effect of quercetin on GBM cells. In conclusion, we suggest quercetin as a potential anticancer agent, which may improve cancer microenvironment of GBM via the Axl/IL-6/STAT3 pathway.


Assuntos
Antineoplásicos Fitogênicos , Apoptose/efeitos dos fármacos , Apoptose/genética , Neoplasias Encefálicas/patologia , Glioblastoma/patologia , Interleucina-6/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Quercetina/farmacologia , Receptores Proteína Tirosina Quinases/metabolismo , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/genética , Neoplasias Encefálicas/tratamento farmacológico , Glioblastoma/tratamento farmacológico , Humanos , Fitoterapia , Quercetina/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Células Tumorais Cultivadas , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/genética
13.
Medicine (Baltimore) ; 100(11): e25107, 2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33725988

RESUMO

BACKGROUND: Pharmacopuncture is a combination of acupuncture and herbal medicine, which involves the injection of herbal extracts into acupuncture points (acupoints). Pharmacopuncture has become one of the major therapeutic tools used in Korea; however, safety is one of the major concerns associated with it. We aim to systematically review clinical studies on the adverse events of pharmacopuncture in Korea. METHODS: To collect data on the incidence and characteristics of adverse events (AEs) and to evaluate pharmacopuncture safety, 2 or more researchers will conduct a comprehensive search of pertinent English and Korean databases using the keywords "pharmacopuncture" and "adverse events." Regardless of the participants' conditions or treatment types, we will include clinical studies on the AEs of pharmacopuncture. Studies that were not conducted in Korea, and acupoint injections containing Western medications, vitamins, or autologous serum will be excluded from this study. The severity of AEs will be classified using the common terminology criteria for adverse events, and the causality between pharmacopuncture and AEs will be assessed using the World Health Organization-Uppsala Monitoring Centre (WHO-UMC) causality scale. The quality of identifying and reporting the AEs will be assessed using the McHarm scale. The risk of selection bias will be assessed using the Cochrane risk of bias and the risk of bias for non-randomized studies tools. Studies will be assessed for heterogeneity utilizing Higgins's I2 statistics, and the risk of publication bias will be assessed and expressed in the form of a contour-enhanced funnel plot. RESULTS AND CONCLUSION: Comprehensive investigation of all types of clinical studies in Korea will provide clearer evidence of the safety of pharmacopuncture. The results of this study will be useful for traditional medical doctors and patients who use such treatments and interventions.Systematic Review Registration: Open Science Foundation (osf.io/umhyz).


Assuntos
Terapia por Acupuntura/efeitos adversos , Medicina Tradicional do Leste Asiático/efeitos adversos , Fitoterapia/efeitos adversos , Pontos de Acupuntura , Terapia por Acupuntura/métodos , Humanos , Medicina Tradicional do Leste Asiático/métodos , Metanálise como Assunto , Fitoterapia/métodos , Preparações de Plantas/administração & dosagem , Preparações de Plantas/efeitos adversos , República da Coreia , Projetos de Pesquisa , Revisões Sistemáticas como Assunto , Resultado do Tratamento
15.
Am J Rhinol Allergy ; : 1945892421998260, 2021 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-33631947

RESUMO

BACKGROUND: There is no trial to make a diagnostic tool of allergic rhinitis (AR) utilizing biomarkers from nasal fluid. Base on previous studies, we selected following five biomarkers in nasal fluids that represent the characteristics of allergic reactions: tryptase, eosinophil cationic protein (ECP), interleukin 5 (IL-5), Clara cell protein 16 (CC16) and CC16-to-albumin ratio. OBJECTIVE: This study aimed to identify biomarkers in nasal discharge that may be used in biosensors to diagnose AR as an additional diagnostic tool. METHODS: Patients showed rhinorrhea and tested positive on allergic skin and specific immunoglobulin E (IgE) tests were included in the AR group. The non-AR group included individuals no dominant nasal symptoms and tested negative on allergy tests. Nasal lavage fluid samples were collected from all participants. Biomarkers in the samples were quantified using enzyme-linked immunosorbent assay. RESULTS: Forty-five patients with AR and 28 non-AR subjects were enrolled in this study. Comparing the concentrations of biomarkers, the concentrations of tryptase and IL-5 were significantly higher in the AR group than in the NAR group. And CC16 level and CC16-to-albumin ratio were significantly lower in the AR group. In the combination of tryptase or CC16-to-albumin ratio, the sensitivity was 90.7% and the specificity was 64.3% (p = 0.013). CONCLUSION: The combination of "tryptase or CC16-to-albumin" could be used as a screening tool for AR. Although this diagnostic method could not replace conventional diagnostic tools, we could consider the method we proposed as an additional screening tool for patients who could not undergo allergy tests.

16.
Phytother Res ; 35(2): 1080-1088, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32935429

RESUMO

Though Sanggenon G (SanG) from root bark of Morus alba was known to exhibit anti-oxidant and anti-depressant effects, its underlying mechanisms still remain unclear. Herein SanG reduced the viability of A549 and H1299 non-small lung cancer cells (NSCLCs). Also, SanG increased sub-G1 population via inhibition of cyclin D1, cyclin E, CDK2, CDK4 and Bcl-2, cleavages of poly (ADP-ribose) polymerase (PARP) and caspase-3 in A549 and H1299 cells. Of note, SanG effectively inhibited c-Myc expression by activating ribosomal protein L5 (RPL5) and reducing c-Myc stability even in the presence of cycloheximide and 20% serum in A549 cells. Furthermore, SanG enhanced the apoptotic effect with doxorubicin in A549 cells. Taken together, our results for the first time provide novel evidence that SanG suppresses proliferation and induces apoptosis via caspase-3 activation and RPL5 mediated inhibition of c-Myc with combinational potential with doxorubicin.


Assuntos
Benzofuranos/química , Carcinoma Pulmonar de Células não Pequenas/genética , Cromonas/química , Genes myc/genética , Neoplasias Pulmonares/genética , Proteínas Ribossômicas/metabolismo , Apoptose , Linhagem Celular Tumoral , Humanos , Transfecção
17.
Brain Behav Immun ; 93: 384-398, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33309911

RESUMO

Gintonin (GT), a glycolipoprotein fraction isolated from ginseng, exerts neuroprotective effects in models of neurodegenerative diseases such as Alzheimer's disease. However, the in vivo role of GT in multiple sclerosis (MS) has not been clearly resolved. We investigated the effect of GT in myelin oligodendrocyte glycoprotein (MOG35-55)-induced experimental autoimmune encephalomyelitis (EAE), an animal model of MS. GT alleviated behavioral symptoms of EAE associated with reduced demyelination, diminished infiltration and activation of immune cells (microglia and macrophage), and decreased expression of inflammatory mediators in the spinal cord of the EAE group compared to that of the sham group. GT reduced the percentages of CD4+/IFN-γ+ (Th1) and CD4+/IL-17+ (Th17) cells but increased the population of CD4+/CD25+/Foxp3+ (Treg) cells in the spinal cord, in agreement with altered mRNA expression of IFN-γ, IL-17, and TGF-ß in the spinal cord in concordance with mitigated blood-brain barrier disruption. The underlying mechanism is related to inhibition of the ERK and p38 mitogen-activated protein kinases (MAPKs) and nuclear factor-kappa B (NF-κB) pathways and the stabilization of nuclear factor erythroid 2-related factor 2 (Nrf2) via increased expression of lysophosphatidic acid receptor (LPAR) 1-3. Impressively, these beneficial effects of GT were completely neutralized by inhibiting LPARs with Ki16425, a LPAR1/3 antagonist. Our results strongly suggest that GT may be able to alleviate EAE due to its anti-inflammatory and antioxidant activities through LPARs. Therefore, GT is a potential therapeutic option for treating autoimmune disorders including MS.


Assuntos
Encefalomielite Autoimune Experimental , Animais , Citocinas , Encefalomielite Autoimune Experimental/tratamento farmacológico , Camundongos , Camundongos Endogâmicos C57BL , Glicoproteína Mielina-Oligodendrócito , Fator 2 Relacionado a NF-E2 , Extratos Vegetais , Receptores de Ácidos Lisofosfatídicos , Medula Espinal
18.
Medicine (Baltimore) ; 99(50): e21820, 2020 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-33327222

RESUMO

BACKGROUND: Although randomized controlled trials have revealed the considerable effectiveness of acupuncture in breast cancer patients, there have been no studies exploring current acupuncture research trends for treatment induced various symptoms in breast cancer patients. This review evaluated the effectiveness of acupuncture for treatment-induced symptoms in breast cancer patients. METHODS: We performed a systematic review and meta-analysis of the literature regarding acupuncture to treat symptoms associated with breast cancer therapies. The following databases were searched for relevant RCTs published before June 2018: MEDLINE, EMBASE, the Cochrane Library, AMED, CINAHL, OASIS, CNKI, and CiNii. RESULTS: Among the 19,483 records identified, 835 articles remained after screening titles and abstracts. A total of 19 RCTs were included in this qualitative synthesis. Among the studies, 8 explored climacteric symptoms, 4 explored pain, 2 explored lymphedemas, 2 explored nausea and vomiting and 3 investigated miscellaneous symptoms.explored miscellaneous symptoms due to cancer treatments. Most of the studies reported that acupuncture can alleviate various symptoms of breast cancer treatment. However, there is a lack of evidence as to whether accupuncture can alleviate chemotherapy associated side effects CONCLUSIONS:: Acupuncture may alleviate the treatment-related symptoms of breast cancer; however, further studies are necessary to obtain conclusive evidence of the effectiveness of acupuncture in treating breast cancer. REGISTRATION NUMBER: CRD42018087813.


Assuntos
Terapia por Acupuntura/métodos , Linfedema Relacionado a Câncer de Mama/terapia , Neoplasias da Mama/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/patologia , Estudos de Casos e Controles , Estudos de Avaliação como Assunto , Feminino , Fogachos/terapia , Humanos , Pessoa de Meia-Idade , Náusea/terapia , Manejo da Dor/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Vômito/terapia
19.
Sci Rep ; 10(1): 19834, 2020 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-33199761

RESUMO

The root of Platycodon grandiflorum (PG) has long been used as a traditional herbal medicine in Asian country. Platycondin D (PD), triterpenoid saponin that is a main constituent of PG, exhibits various biological activities such as anti-inflammatory, anti-oxidant, anti-diabetic, and anti-cancer effects. A previous study showed that PD had cholesterol-lowering effects in mice that develop hypercholesterolemia, but the underlying molecular mechanisms have not been elucidated during the last decade. Here, we demonstrated that both PG and PD markedly increased levels of cell surface low-density lipoprotein receptor (LDLR) by down-regulation of the E3 ubiquitin ligase named inducible degrader of the LDLR (IDOL) mRNA, leading to the enhanced uptake of LDL-derived cholesterol (LDL-C) in hepatic cells. Furthermore, cycloheximide chase analysis and in vivo ubiquitination assay revealed that PD increased the half-life of LDLR protein by reducing IDOL-mediated LDLR ubiquitination. Finally, we demonstrated that treatment of HepG2 cells with simvastatin in combination with PG and PD had synergistic effects on the improvement of LDLR expression and LDL-C uptake. Together, these results provide the first molecular evidence for anti-hypercholesterolemic activity of PD and suggest that PD alone or together with statin could be a potential therapeutic option in the treatment of atherosclerotic cardiovascular disease.


Assuntos
LDL-Colesterol/metabolismo , Hepatócitos/metabolismo , Platycodon/química , Receptores de LDL/metabolismo , Saponinas/farmacologia , Triterpenos/farmacologia , Ubiquitina-Proteína Ligases/genética , Linhagem Celular , Cicloeximida/farmacologia , Sinergismo Farmacológico , Regulação da Expressão Gênica/efeitos dos fármacos , Meia-Vida , Células Hep G2 , Hepatócitos/citologia , Hepatócitos/efeitos dos fármacos , Humanos , Raízes de Plantas/química , Sinvastatina/farmacologia , Ubiquitinação
20.
Artigo em Inglês | MEDLINE | ID: mdl-33029168

RESUMO

Pancreatic cancer has a poor prognosis with a five-year survival rate of less than 10%. Moreover, chemotherapy is mostly rendered ineffective owing to chemotherapy resistance and cytotoxicity. Therefore, the development of effective therapeutic strategies and novel drugs against pancreatic cancer is an urgent need. Cucurbitacin D (CuD), a plant steroid derived from Trichosanthes kirilowii, is an anticancer agent effective against various cancer cell lines. However, the anticancer activity and molecular mechanism of CuD in pancreatic cancer remain unknown. Therefore, we aimed to investigate the anticancer activity and molecular mechanism of CuD in the human pancreatic cancer cell line, Capan-1. CuD induced cell cycle arrest at the G2/M phase, apoptosis, and reactive oxygen species generation in Capan-1 cell line. In addition, CuD induced the activation of the p38 MAPK signaling pathway that regulates apoptosis, which was also inhibited by N-acetyl-L-cysteine and the p38 inhibitor SB203580. These data suggest that CuD induces cell cycle arrest and apoptosis via the ROS/p38 pathway in Capan-1 pancreatic cancer cell line; hence, CuD is a promising candidate that should be explored further for its effectiveness as an anticancer agent against pancreatic cancer.

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