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1.
Virology ; 543: 13-19, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-32056842

RESUMO

Orthohantaviruses are negative-sense, single-stranded RNA viruses harbored by rodents, shrews, moles, and bats. Of the shrew-borne orthohantaviruses in the Republic of Korea (ROK), Jeju orthohantavirus (Jeju virus, JJUV) was found on Jeju Island. This small-scale epidemiologic survey investigated the geographic distribution and molecular phylogeny of JJUV in the ROK. In 32 trapping sites, tissues of 84 Crocidura shantungensis were analyzed for JJUV RNA. JJUV RNA was detected in seven (8.3%) shrews captured on the Korean peninsula. The molecular epidemiologic survey demonstrated the prevalence of JJUV by geographic distribution. The RNA loads of JJUV were evaluated in various tissues. Entire coding sequences of tripartite genomes were recovered from two JJUV strains on the mainland. Phylogenetic relationships of the JJUV revealed a distinct geographic lineage of mainland strains from the strains on Jeju Island. This study sheds light on the molecular epidemiology, phylogeographic diversity, and virus-host co-divergence of JJUV, ROK.

2.
Int J Mol Sci ; 21(4)2020 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-32079309

RESUMO

Overexpression of human epidermal growth factor receptor type 2 (HER2) is considered as a prognostic factor of breast cancer, which is positively associated with recurrence when cancer metastasizes to the lymph nodes. Here, we expressed the single variable domain on a heavy chain (VHH) form of anti-HER2 camelid single domain antibody in tobacco plants and compared its in vitro anticancer activities with the anti-HER2 full size antibody. The gene expression cassette containing anti-HER2 camelid single domain antibody VHH fused to human IgG Fc region with KDEL endoplasmic reticulum (ER) (VHH-FcK) was transferred into the tobacco plant via the Agrobacterium-mediated transformation. The transformants were screened with polymerase chain reaction and Western blot analyses. Enzyme-linked immunosorbent assay (ELISA) confirmed the binding of the purified anti-HER2 VHH-FcK to the HER2-positive breast cancer cell line, SK-BR-3. Migration assay results confirmed anticancer activity of the plant-derived anticancer camelid single chain antibody. Taken together, we confirmed the possibility of using anti-HER2 VHH-FcK as a therapeutic anticancer agent, which can be expressed and assembled and purified from a plant expression system as an alternative antibody production system.

3.
Complement Ther Med ; 48: 102246, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31987248

RESUMO

OBJECTIVES: Chronic fatigue (CF) is unexplained fatigue lasting more than 6 months. Korean red ginseng (KRG) is known to have higher anti-fatigue substance than white ginseng. However, its efficacy and safety for CF is unknown. The purpose of this study was to investigate the effect of KRG on CF by various measurements and objective indicators. DESIGN: A randomized, double-blind, clinical trial was conducted on 50 patients with CF. INTERVENTION: Participants were allocated to KRG or placebo group (1:1 ratio) and visited hospital every 2 weeks during taking 3 g KRG or placebo for 6 weeks and followed up 4 weeks after the treatment. MAIN OUTCOME MEASURES: The primary outcome measurement was fatigue VAS. Secondary outcome measurements included FSS, CFSQ, SRI, scales of various fields (Depression: BDI; Sleep: ISI; Quality of life: EQ-5D 5 L), biochemical test (Antioxidants: d-ROMs, TBARS, BAP, and SOD; Cortisol concentration: salivary cortisol), blinding assessment, and adverse events. RESULTS: The fatigue VAS declined significantly in each group, but there were no significant differences between the groups. The 2 groups also had no significant differences in the secondary outcome measurements and there were no adverse events. Sub-group analysis indicated that patients with initial fatigue VAS below 80 mm and older than 50 years had significantly greater reductions in the fatigue VAS if they used KRG rather than placebo. CONCLUSIONS: By our study, KRG did not show absolute anti-fatigue effect but provided the objective evidence of fatigue-related measurement and the therapeutic potential for middle-aged individuals with moderate fatigue.

4.
Clin Infect Dis ; 70(3): 464-473, 2020 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-30891596

RESUMO

BACKGROUND: Endemic outbreaks of hantaviruses pose a critical public health threat worldwide. Hantaan orthohantavirus (HTNV) causes hemorrhagic fever with renal syndrome (HFRS) in humans. Using comparative genomic analyses of partial and nearly complete sequences of HTNV from humans and rodents, we were able to localize, with limitations, the putative infection locations for HFRS patients. Partial sequences might not reflect precise phylogenetic positions over the whole-genome sequences; finer granularity of rodent sampling reflects more precisely the circulation of strains. METHODS: Five HFRS specimens were collected. Epidemiological surveys were conducted with the patients during hospitalization. We conducted active surveillance at suspected HFRS outbreak areas. We performed multiplex polymerase chain reaction-based next-generation sequencing to obtain the genomic sequence of HTNV from patients and rodents. The phylogeny of human- and rodent-derived HTNV was generated using the maximum likelihood method. For phylogeographic analyses, the tracing of HTNV genomes from HFRS patients was defined on the bases of epidemiological interviews, phylogenetic patterns of the viruses, and geographic locations of HTNV-positive rodents. RESULTS: The phylogeographic analyses demonstrated genetic clusters of HTNV strains from clinical specimens, with HTNV circulating in rodents at suspected sites of patient infections. CONCLUSIONS: This study demonstrates a major shift in molecular epidemiological surveillance of HTNV. Active targeted surveillance was performed at sites of suspected infections, allowing the high-resolution phylogeographic analysis to reveal the site of emergence of HTNV. We posit that this novel approach will make it possible to identify infectious sources, perform disease risk assessment, and implement preparedness against vector-borne viruses.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31814199

RESUMO

AIM: To evaluate the effectiveness of adjuvant treatment for morcellated, uterus-confined leiomyosarcoma in a multicenter setting. METHODS: We identified patients with International Federation of Gynecology and Obstetrics stage I uterine leiomyosarcoma primarily treated with surgery between 2003 and 2016. Among them, patients who underwent one of the following morcellation methods were included: (i) power morcellation; (ii) intracorporeal morcellation using scalpels or electrocautery; and (iii) vaginal morcellation. Patients' survival outcomes were compared according to the implementation of adjuvant treatment. RESULTS: From 13 institutions, 55 patients were included; 31 for adjuvant treatment group and 24 for surgery only group. The clinicopathological characteristics including the mass size, morcellation methods, extent of surgery, and mitotic count were similar between the groups. In the adjuvant treatment group, 67.7%, 19.4% and 12.9% of patients received chemotherapy, chemoradiation and radiation, respectively. After a median follow-up of 50.5 months, the adjuvant treatment and surgery only groups showed similar overall survival (5-year rate, 92.0% vs 90.4%; P = 0.959). No significant difference in progression-free survival was observed between the two groups (3-year rate, 46.1% vs 78.2%; P = 0.069). On multivariate analyses, adjuvant treatment did not affect progression-free survival (adjusted HR, 2.138; 95% CI, 0.550-8.305; P = 0.273). The adjuvant treatment group showed a trend towards more common distant metastasis, compared to the surgery only group (25.8% vs 4.2%; P = 0.062). The incidences of pelvic, retroperitoneal, and abdominal recurrences were not different between the groups. CONCLUSION: Despite its frequent use in clinical practice, adjuvant treatment did not improve the survival outcomes of patients with morcellated, International Federation of Gynecology and Obstetrics stage I uterine leiomyosarcoma.

6.
J Control Release ; 318: 176-184, 2019 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-31838204

RESUMO

We propose the use of an implantable device with multiple embedded drug diffusion channels, each of which is connected to a drug reservoir, for the controlled release of diclofenac. To minimize the size of the incision needed during device implantation, the device used herein was made of the soft biocompatible material polydimethylsiloxane (PDMS), thereby allowing for folding during device implantation. We aimed to achieve a profile of diclofenac release that was reproducible even after folding, and thus the channel was filled with cross-linked gelatin, which could be swollen via the infiltration of a bodily fluid to compensate for any possible defects formed during folding. We first assessed the use of individual channels of varying lengths of 1-12 mm, and the onset time and average rate varied from 1 to 14 days and from 0.31-4.3%/day, respectively. According to these results, we prepared a device with multiple integrated pairs of drug reservoirs and channels of different lengths (i.e., the SDD_I), in which the channel combination was selected to achieve the long-term, zero-order release of the largest amount of drug. Thus, the SDD_I used herein exhibited almost zero-order drug release for 55 days at a release rate of 1.19%/day (179.8 µg/day), which did not vary even after the device was folded multiple times due to the presence of gelatin in the channel. When tested in living rats, the SDD_I device could be folded and inserted subcutaneously through an incision less than half the size of that needed for the implantation of the unfolded, intact SDD_I. For both the unfolded and folded SDD_I devices, the drug concentration in blood was observed to be maintained within a similar range due to the almost zero-order, reproducible release of diclofenac.

7.
Opt Express ; 27(24): 35842-35855, 2019 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-31878750

RESUMO

We have developed a simple method to quantify randomness in photonic glasses in relation to the ideal random limit, using autocorrelation functions obtained from two-dimensional images. In our case, the photonic glasses consist of randomly packed silica microspheres which serve as a model system representing isotropic random media. Conventional methods of characterizing randomness in photonic materials often entail technical complexities, such as chemical functionalization, three-dimensional rendering, and particle tracking. Our method circumvents these difficulties based on a mathematical relation that we derive between the autocorrelation function and the radial distribution function. This relation enables us to find the autocorrelation function in the ideal random limit. The autocorrelation function of experimentally fabricated photonic glasses is then obtained from images of a single cross-sectional plane and directly compared to that of the ideal limit. The comparison shows that the autocorrelation function of real structures deviates only slightly from the ideal limit. We find that the deviation can be explained in part by the microsphere polydispersity. Our general method would be useful in characterizing a large class of photonic random media, encompassing biological materials, radiative cooling coatings, and random lasing photonic glasses.

8.
J Ginseng Res ; 43(4): 666-675, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31700262

RESUMO

Background: Korean Red Ginseng (KRG) has been widely used as an herbal medicine to normalize and strengthen body functions. Although many researchers have focused on the biological effects of KRG, more studies on the action mechanism of red ginseng are still needed. Previously, we investigated the proteomic changes of the rat spleen while searching for molecular signatures and the action mechanism of KRG. The proteomic analysis revealed that differentially expressed proteins (DEPs) were involved in the increased immune response and phagocytosis. The aim of this study was to evaluate the biological activities of KRG, especially the immune-enhancing response of KRG. Methods: Rats were divided into 4 groups: 0 (control group), 500, 1000, and 2000 mg/kg administration of KRG powder for 6 weeks, respectively. Isobaric tags for relative and absolute quantitation was performed with Q-Exactive LC-MS/MS to compare associated proteins between the groups. The putative DEPs were identified by a current UniProt rat protein database search and by the Gene Ontology annotations. Results: The DEPs appear to increase the innate and acquired immunity as well as immune cell movement. These results suggest that KRG can stimulate immune responses. This analysis refined our targets of interest to include the potential functions of KRG. Furthermore, we validated the potential molecular targets of the functions, representatively LCN2, CRAMP, and HLA-DQB1, by Western blotting. Conclusion: These results may provide molecular signature candidates to elucidate the mechanisms of the immune response by KRG. Here, we demonstrate a strategy of tissue proteomics for the discovery of the molecular function of KRG.

9.
Sci Rep ; 9(1): 16631, 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31719616

RESUMO

Orthohantaviruses, negative-sense single-strand tripartite RNA viruses, are a global public health threat. In humans, orthohantavirus infection causes hemorrhagic fever with renal syndrome or hantavirus cardiopulmonary syndrome. Whole-genome sequencing of the virus helps in identification and characterization of emerging or re-emerging viruses. Next-generation sequencing (NGS) is a potent method to sequence the viral genome, using molecular enrichment methods, from clinical specimens containing low virus titers. Hence, a comparative study on the target enrichment NGS methods is required for whole-genome sequencing of orthohantavirus in clinical samples. In this study, we used the sequence-independent, single-primer amplification, target capture, and amplicon NGS for whole-genome sequencing of Hantaan orthohantavirus (HTNV) from rodent specimens. We analyzed the coverage of the HTNV genome based on the viral RNA copy number, which is quantified by real-time quantitative PCR. Target capture and amplicon NGS demonstrated a high coverage rate of HTNV in Apodemus agrarius lung tissues containing up to 103-104 copies/µL of HTNV RNA. Furthermore, the amplicon NGS showed a 10-fold (102 copies/µL) higher sensitivity than the target capture NGS. This report provides useful insights into target enrichment NGS for whole-genome sequencing of orthohantaviruses without cultivating the viruses.

10.
J Microbiol Biotechnol ; 29(11): 1693-1706, 2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31546298

RESUMO

Atopic dermatitis (AD) is a chronic inflammatory skin disease of mainly infants and children. Currently, the development of safe and effective treatments for AD is urgently required. The present study was conducted to investigate the immunomodulatory effects of yeast-extracted ß-1,3/1,6-glucan and/or Lactobacillus plantarum (L. plantarum) LM1004 against AD-like symptoms. To purpose, ß-1,3/1,6-glucan and/or L. plantarum LM1004 were orally administered to AD-induced animal models of rat (histamine-induced vasodilation) and mouse (pruritus and contact dermatitis) exhibiting different symptoms of AD. We then investigated the treatment effects on AD-like symptoms, gene expression of immune-related factors, and gut microbiomes. Oral administration of ß-1,3/1,6-glucan (0.01 g/kg initial body weight) and/or 2 × 1012 cells/g L. plantarum LM1004 (0.01 g/kg initial body weight) to ADinduced animal models showed significantly reduced vasodilation in the rat model, and pruritus, edema, and serum histamine in the mouse models (p < 0.05). Interestingly, ß-1,3/1,6- glucan and/or L. plantarum LM1004 significantly decreased the mRNA levels of Th2 and Th17 cell transcription factors, while the transcription factors of Th1 and Treg cells, galactin-9, filaggrin increased, which are indicative of enhanced immunomodulation (p < 0.05). Moreover, in rats with no AD induction, the same treatments significantly increased the relative abundance of phylum Bacteroidetes and the genus Bacteroides. Furthermore, bacterial taxa associated with butyrate production such as, Lachnospiraceae and Ruminococcaceae at family, and Roseburia at genus level were increased in the treated groups. These findings suggest that the dietary supplementation of ß-1,3/1,6-glucan and/or L. plantarum LM1004 has a great potential for treatment of AD as well as obesity in humans through mechanisms that might involve modulation of host immune systems and gut microbiota.

11.
Sci Rep ; 9(1): 12868, 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31477793

RESUMO

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

13.
Phytomedicine ; 63: 153019, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31302317

RESUMO

BACKGROUND: Obovatol, a biphenolic chemical originating from Magnolia obovata, has been utilized as a traditional medicine for the treatment of inflammatory diseases. Inflammasome induces maturation of inflammatory cytokines in response to intracellular danger signals, and its dysregulation induces inflammatory diseases. PURPOSE: The effect of obovatol on inflammasome activation has not been reported, although its anti-inflammatory properties have been studied. STUDY DESIGN/METHODS: Obovatol was treated to macrophages with inflammasome triggers, and secretions of interleukin (IL)-1ß, IL-18, and caspase-1 were measured as readouts of inflammasome activation. In addition, Asc pyroptosome formation, caspase-1 activity, and mitochondrial reactive oxygen species (ROS) production were analyzed in mechanical studies. Anti-inflammasome properties of obovatol were confirmed in an animal model. RESULTS: Obovatol inhibited NLRP3, AIM2, and non-canonical inflammasomes through inhibition of Asc pyroptosome formation and mitochondrial ROS generation. In addition, obovatol disrupted the priming step of inflammasome activation and inhibited transcription of inflammatory cytokines. In mice, obovatol attenuated serum IL-1ß elevation in response to monosodium urate crystals. CONCLUSION: Obovatol is suggested as an inhibitor of NLRP3, AIM2, and non-canonical inflammasomes.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Compostos de Bifenilo/farmacologia , Proteínas de Ligação a DNA/antagonistas & inibidores , Inflamassomos/efeitos dos fármacos , Proteína 3 que Contém Domínio de Pirina da Família NLR/antagonistas & inibidores , Éteres Fenílicos/farmacologia , Animais , Anti-Inflamatórios não Esteroides/química , Compostos de Bifenilo/química , Caspase 1/metabolismo , Citocinas/genética , Citocinas/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Modelos Animais de Doenças , Feminino , Humanos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos Endogâmicos C57BL , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Peritonite/tratamento farmacológico , Éteres Fenílicos/química , Espécies Reativas de Oxigênio/metabolismo , Ácido Úrico/farmacologia
14.
Dermatol Ther ; 32(5): e13037, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31361931

RESUMO

Frontal fibrosing alopecia (FFA) is an inflammatory disorder characterized by scarring alopecia of the frontotemporal scalp, thinning or loss of facial hair, and facial papules. Prompt treatment is essential to prevent permanent hair loss. Although studies have reported the efficacy of oral retinoids (isotretinoin and acitretin) in FFA treatment, a therapeutic role for alitretinoin is known only for lichen planus and not for FFA. Herein, we report a case of FFA accompanied with lichen planus that responded well to treatment with alitretinoin.

15.
Proc Natl Acad Sci U S A ; 116(24): 11664-11672, 2019 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-31123147

RESUMO

Implantable devices for on-demand and pulsatile drug delivery have attracted considerable attention; however, many devices in clinical use are embedded with the electronic units and battery inside, hence making them large and heavy for implantation. Therefore, we propose an implantable device with multiple drug reservoirs capped with a stimulus-responsive membrane (SRM) for on-demand and pulsatile drug delivery. The SRM is made of thermosensitive POSS(MEO2MA-co-OEGMA) and photothermal nanoparticles of reduced graphene oxide (rGO), and each of the drug reservoirs is filled with the same amount of human growth hormone (hGH). Therefore, with noninvasive near-infrared (NIR) irradiation from the outside skin, the rGO nanoparticles generate heat to rupture the SRM in the implanted device, which can open a single selected drug reservoir to release hGH. Therefore, the device herein is shown to release hGH reproducibly only at the times of NIR irradiation without drug leakage during no irradiation. When implanted in rats with growth hormone deficiency and irradiated with an NIR light from the outside skin, the device exhibits profiles of hGH and IGF1 plasma concentrations, as well as body weight change, similar to those in animals treated with conventional s.c. hGH injections.

16.
Medicine (Baltimore) ; 98(19): e15574, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31083232

RESUMO

BACKGROUND: Hypertension and type 2 diabetes are chronic diseases, which generally require lifetime care. Meditation and yoga can be complementary to pharmacological therapies according to the scientific evidences so far. Brain education-based meditation (BEM) is a technique, which has been known to change brain structure, psychology, and physiology of healthy adult participants. This randomized, nonblinded pilot trial aimed to examine whether BEM affects the conditions of patients with hypertension and/or type 2 diabetes compared with health education classes. METHODS: We randomly allocated 48 patients with hypertension and/or type 2 diabetes to BEM (n = 24) or health education (n = 24) classes in the Ulsan Junggu Public Health Center in Korea, where the classes were run during the same period and explored the impact of 8-week practice on the serum glutamic-oxaloacetic transaminase, serum glutamic pyruvic transaminase, gamma glutamyl transpeptidase, creatinine, high-density lipoprotein cholesterol, and low-density lipoprotein (LDL) cholesterol. Total RNA was extracted to examine inflammatory gene expressions from the whole blood using PAXgene blood RNA System. In addition, self-reports on mental/physical health were evaluated. The Student's t test, chi-squared test, and analysis of covariance were used for statistical analysis. RESULTS: The number of people who participated until the completion of the study was 14 in the control and 21 in the BEM group. After 8 weeks, LDL cholesterol level was significantly decreased in the BEM group after the intervention (13.82 mg/dL reduction, P < .05), while it was not significantly altered in the control group. The expression of inflammatory genes was significantly reduced after 8 weeks of the BEM training (0.3-, 0.5-, and 0.2-fold change for NFKB2, RELA, and IL1B, respectively, all P < .05). In the item analysis of mental/physical health self-reports, a significant improvement was confirmed as follows: increases in focus, confidence, relaxation, and happiness; decreases in fatigue, anger, and loneliness (all P < .05). There were no important adverse events or side-effects by BEM intervention. CONCLUSION: Compared to health education, BEM helps lower LDL cholesterol level and the inflammatory gene expression in the patients with hypertension and/or type 2 diabetes. Moreover, BEM induces positive effects on the self-reported mental/physical states, warranting further study.


Assuntos
Diabetes Mellitus Tipo 2/terapia , Hipertensão/terapia , Meditação , Educação de Pacientes como Assunto , Idoso , Biomarcadores/sangue , LDL-Colesterol/sangue , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/psicologia , Feminino , Expressão Gênica , Humanos , Hipertensão/sangue , Hipertensão/complicações , Hipertensão/psicologia , Inflamação/sangue , Masculino , Projetos Piloto
17.
J Nanosci Nanotechnol ; 19(10): 6187-6191, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31026934

RESUMO

Diabetes mellitus is a common disease that has affected people since antiquity. The complexity of diabetes mellitus lies in the fact that it requires continuous management in order to prevent serious complications. Various methods for managing diabetes mellitus through monitoring blood glucose levels have been studied and developed, and the most widely used method includes using an invasive blood glucose meter. Since the invasive blood glucose meter poses a major inconvenience for patients, in this study, we sought to develop a non-invasive blood glucose meter. We therefore proposed the development of a non-invasive blood glucose measurement system that is based on near-infrared spectroscopy. The system developed was composed of a light source for emitting different wavelengths, a light detector unit, and a computing system for recording signals. A prepared glucose solution was injected into a quartz cuvette and light at 780-1650 nm was emitted to pass through the cuvette. The degree of reaction was determined by recording the change in wavelength. The wavelength band used for the experiment was 780-1000 nm and the resolution was 20 nm. The glucose concentration was determined to be between 50 to 400 mg/dl compared to the normal range of 80 to 120 mg/dl. By examining which wavelength bands specifically reacted with glucose, we observed that the wavelength bands that decreased or increased in response to the glucose concentration were at 780 nm and 940 nm. For wavelength bands at 1000 nm or above, light was also absorbed by water and therefore it was difficult to distinguish the results. The most reliable wavelength band was at 940 nm with an R² of 0.9806. In conclusion, the near-infrared light emitting diode based non-invasive glucose detection system performed well and is expected to be a superior method for monitoring blood glucose levels in diabetes mellitus.

18.
J Nanosci Nanotechnol ; 19(10): 6546-6553, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31026991

RESUMO

Rheumatoid arthritis is a chronic inflammatory disease that affects joints and induces pain and swelling. We evaluated the anti-inflammatory effects of step electrical stimulation (SES) in this study. SES was carried out by increasing the voltage (3 V/s) from 5 V to 100 V for 60 cycles. The viability of mouse embryonic fibroblasts (NIH-3T3) was evaluated after step-electrical stimulation. After the injection of complete Freund's adjuvant (CFA) on the right hind paw of Sprague Dawley (SD) rats (6 weeks old), the degree of swelling was measured using a digital plethysmometer and Vernier caliper. Histological changes in inflamed tissues were observed with hematoxylin and eosin (H&E) staining, while the degree of inflammation was evaluated from the expression level of inflammatory factors such as cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6). As a result, we found no difference in cell viability after SES treatment between the control and SES-treated groups. On day 21 after CFA injection, the swelling of right hind paws decreased by 1.09 times in SES-treated group as compared with the untreated group. In addition, the levels of COX-2, TNF-α and IL-6 significantly decreased after SES treatment. Thus, SES treatment decreased paw swelling and alleviated inflammation.

19.
Cancers (Basel) ; 11(4)2019 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-30965654

RESUMO

: Drug resistance is one of the major characteristics of cancer stem cells (CSCs) and a mechanism of tumor recurrence. Therefore, selectively targeting CSCs may be an effective therapeutic strategy to overcome cancer recurrence. In the present study, we found that exposure to tumorigenic compounds significantly increased the growth potential and stem-cell-like properties of various CSCs. Early-response genes involved in tumorigenesis can be used as specific markers to predict potential tumorigenicity. Importantly, for the first time we identified, a labile tumorigenic response gene-SERPINB2-and showed that tumorigenic compound exposure more profoundly affected its expression in CSCs than in non-stem cancer cells, although both cells exhibit basal expression of SERPINB2 in multiple cancer types. Our data also revealed a strong relationship between the significantly enhanced expression of SERPINB2 and metastatic progression in multiple cancer types. To the best of our knowledge, this is the first study to focus on the functions of SERPINB2 in the tumorigenicity of various CSCs and these findings will facilitate the development of promising tumorigenicity test platforms.

20.
J Ginseng Res ; 43(2): 291-299, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30976167

RESUMO

Background: Ginsenosides of Korean Red Ginseng extracts (RGE) and its saponin components suppress secretion of inflammasome-mediating cytokines, whereas the nonsaponin fraction (NS) of RGE oppositely stimulates cytokine secretion. Although direct exposure of NS to macrophages in mice induces cytokine production, oral administration of NS has not been studied in inflammasome-related disease in animal models. Methods: Mice were fed RGE or NS for 7 days and then developed peritonitis. Peritoneal cytokines were measured, and peritoneal exudate cells (PECs) were collected to assay expression levels of a set of toll-like receptors (TLRs) and cytokines in response to NS ingestion. In addition, the role of intestinal bacteria in NS-fed mice was assessed. The effect of preexposure to NS in bone marrow-derived macrophages (BMDMs) on cytokine production was further confirmed. Results: NS ingestion attenuated secretion of peritoneal cytokines resulting from peritonitis. In addition, the isolated PECs from NS-fed mice presented lower TLR transcription levels than PECs from control diet-fed mice. BMDMs treated with NS showed downregulation of TLR4 mRNA and protein expression, which was mediated by the TLR4-MyD88-NFκB signal pathway. BMDMs pretreated with NS produced less cytokines in response to TLR4 ligands. Conclusion: NS administration directly inhibits TLR4 expression in inflammatory cells such as macrophages, thereby reducing secretion of cytokines during peritonitis.

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