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1.
Curr Issues Mol Biol ; 46(6): 6100-6111, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38921035

RESUMO

This study examines the synergistic interaction between the immunomodulatory functions of lactic acid bacteria postbiotics and the anti-inflammatory properties of Smilax china L. extract through a combined fermentation process. Using atopic dermatitis (AD) as a model, characterized by an immune imbalance that leads to skin inflammation, we developed a fermented product, MB-2006, and compared its effects to those of the heat-killed probiotics Lactobacillus acidophilus (LAC) and Lactobacillus rhamnosus (LRH). Our experiments focused on elucidating the mechanism of action of MB-2006 in AD-like HaCaT keratinocyte cells, particularly its impact on the NF-κB pathway, a pivotal regulator of inflammation. MB-2006 proved more effective in reducing inflammation markers, such as IL-4 and thymic stromal lymphopoietin (TSLP), and in inhibiting NF-κB activation compared to LAC and LRH. Significantly, MB-2006 also reduced the expression of thymus- and activation-regulated chemokine (TARC), highlighting a synergistic effect that enhances its therapeutic potential. These results suggest that the combined fermentation of Smilax china L. extract with lactic acid bacteria enhanced both the anti-inflammatory and immunomodulatory effects, presenting a promising integrative approach to treating conditions like AD. Further studies are needed to validate these results in clinical settings and fully explore the potential of this synergistic fermentation process.

2.
Pharmaceuticals (Basel) ; 16(11)2023 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-38004466

RESUMO

Non-alcoholic steatohepatitis (NASH) is a complex disease resulting from chronic liver injury associated with obesity, type 2 diabetes, and inflammation. Recently, the importance of developing multi-target drugs as a strategy to address complex diseases such as NASH has been growing; however, their manufacturing processes remain time- and cost-intensive and inefficient. To overcome these limitations, we developed UniStac, a novel enzyme-mediated conjugation platform for multi-specific drug development. UniStac demonstrated high conjugation yields, optimal thermal stabilities, and robust biological activities. We designed a tetra-specific compound, C-192, targeting glucagon-like peptide 1 (GLP-1), glucagon (GCG), fibroblast growth factor 21 (FGF21), and interleukin-1 receptor antagonist (IL-1RA) simultaneously for the treatment of NASH using UniStac. The biological activity and treatment efficacy of C-192 were confirmed both in vitro and in vivo using a methionine-choline-deficient (MCD) diet-induced mouse model. C-192 exhibited profound therapeutic efficacies compared to conventional drugs, including liraglutide and dulaglutide. C-192 significantly improved alanine transaminase levels, triglyceride accumulation, and the non-alcoholic fatty liver disease activity score. In this study, we demonstrated the feasibility of UniStac in creating multi-specific drugs and confirmed the therapeutic potential of C-192, a drug that integrates multiple mechanisms into a single molecule for the treatment of NASH.

3.
Toxins (Basel) ; 15(7)2023 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-37505738

RESUMO

Species of the marine dinoflagellate genus Karenia are known to produce various potent biotoxins and can form noxious blooms that cause mass mortalities of fish and shellfish. To date, harmful blooms of the species K. mikimotoi have been reported in Korea, but K. papilionacea was recently recorded off the southern coast of Korea. Here, we developed a quantitative real-time PCR (qRT-PCR) assay with specific primer pairs for the accurate detection and quantification of these two similar-looking unarmored species, K. mikimotoi and K. papilionacea, and investigated their distribution and dynamics in Korean coastal waters. Overall, K. papilionacea had not only a wider distribution, but also higher cell abundances (15-2553 cells L-1) than K. mikimotoi (3-122 cells L-1) in surface waters. Of 18 sampling sites, the two Karenia species were found to coexist at two sites. During monitoring at a fixed station (S5), K. papilionacea was generally predominant over K. mikimotoi; however, the two species exhibited similar dynamics and occasionally co-occurred. Both Karenia species showed similar physiological responses to temperature and salinity, requiring similar conditions for optimum growth. These results suggest that blooms of the two species may co-occur and induce a synergistic adverse effect on marine environments.


Assuntos
Dinoflagellida , Animais , Dinoflagellida/genética , Reação em Cadeia da Polimerase em Tempo Real , Temperatura , República da Coreia , Proliferação Nociva de Algas
5.
Am J Eval ; 44(1): 29-49, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37069836

RESUMO

Evaluation capacity building (ECB) continues to attract the attention and interest of scholars and practitioners. Over the years, models, frameworks, strategies, and practices related to ECB have been developed and implemented. Although ECB is highly contextual, the evolution of knowledge in this area depends on learning from past efforts in a structured approach. The purpose of the present article is to integrate the ECB literature in evaluation journals. More specifically, the article aims to answer three questions: What types of articles and themes comprise the current literature on ECB? How are current practices of ECB described in the literature? And what is the current status of research on ECB? Informed by the findings of the review, the article concludes with suggestions for future ECB practice and scholarship.

6.
Exp Mol Med ; 55(5): 1033-1045, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37121980

RESUMO

Memory-phenotype (MP) CD4+ T cells are a substantial population of conventional T cells that exist in steady-state mice, yet their immunological roles in autoimmune disease remain unclear. In this work, we unveil a unique phenotype of MP CD4+ T cells determined by analyzing single-cell transcriptomic data and T cell receptor (TCR) repertoires. We found that steady-state MP CD4+ T cells in the spleen were composed of heterogeneous effector subpopulations and existed regardless of germ and food antigen exposure. Distinct subpopulations of MP CD4+ T cells were specifically activated by IL-1 family cytokines and STAT activators, revealing that the cells exerted TCR-independent bystander effector functions similar to innate lymphoid cells. In particular, CCR6high subpopulation of MP CD4+ T cells were major responders to IL-23 and IL-1ß without MOG35-55 antigen reactivity, which gave them pathogenic Th17 characteristics and allowed them to contribute to autoimmune encephalomyelitis. We identified that Bhlhe40 in CCR6high MP CD4+ T cells as a key regulator of GM-CSF expression through IL-23 and IL-1ß signaling, contributing to central nervous system (CNS) pathology in experimental autoimmune encephalomyelitis. Collectively, our findings reveal the clearly distinct effector-like heterogeneity of MP CD4+ T cells in the steady state and indicate that CCR6high MP CD4+ T cells exacerbate autoimmune neuroinflammation via the Bhlhe40/GM-CSF axis in a bystander manner.


Assuntos
Encefalomielite Autoimune Experimental , Fator Estimulador de Colônias de Granulócitos e Macrófagos , Camundongos , Animais , Fator Estimulador de Colônias de Granulócitos e Macrófagos/genética , Fator Estimulador de Colônias de Granulócitos e Macrófagos/metabolismo , Imunidade Inata , Doenças Neuroinflamatórias , Encefalomielite Autoimune Experimental/metabolismo , Células Th17 , Interleucina-23 , Fenótipo , Receptores de Antígenos de Linfócitos T/metabolismo , Linfócitos T CD4-Positivos , Camundongos Endogâmicos C57BL , Proteínas de Homeodomínio/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética
8.
Soa Chongsonyon Chongsin Uihak ; 32(2): 71-78, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33828406

RESUMO

OBJECTIVES: This study was conducted to investigate the reliability and validity of the Korean version of the DSM-5 Level 2 Cross-Cutting Symptom Measure-inattention [Swanson, Nolan and Pelham, version IV (SNAP-IV)] and anger [Patient-Reported Outcome Measurement Information System (PROMIS) Anger] for parents and guardians of children aged 6-17 years. METHODS: We included 104 children and adolescents diagnosed with attention-deficit/hyperactivity disorder (ADHD), ADHD with anxiety and depression, depressive disorder, anxiety disorder, and tic disorder with somatic symptoms (ADHD=41, depression=9, anxiety=14, ADHD+anxious depression=11, tic+somatic symptoms=29). Their ages ranged from 8 years to 15 years. The participants' mothers completed the SNAP-IV, PROMIS Anger scale, Korean version of the IOWA Conners Rating Scale (K-IOWA), and Korean ADHD Rating Scale (K-ARS) so that the reliability and validity of the SNAP-IV and PROMIS Anger scales, which are DSM-5 scales for assessing inattention and anger of children and adolescents, could be examined. RESULTS: The reliability coefficient of SNAP-IV (Cronbach's α) was 0.94. The correlation coefficients between SNAP-IV, K-IOWA inattention, and K-ARS inattention scores ranged from 0.73 to 0.86. The mean SNAP-IV scores of the ADHD and the ADHD+anxious depression groups were significantly higher than those of the anxiety and the tic+somatic symptoms groups. The reliability coefficient of the PROMIS Anger was 0.91. The correlation coefficient between PROMIS Anger and K-IOWA oppositional/defiant scores was 0.75. The PROMIS Anger mean score of the ADHD+anxious depression group tended to be higher than that of the other groups. CONCLUSION: These results suggest that the Korean version of the DSM-5 Level 2 Cross-Cutting Symptom Measure-inattention and anger for parent and guardian of child age 6-17 might be a reliable and valid test and may be useful for screening children and adolescents with ADHD.

9.
J Affect Disord ; 282: 885-893, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33601732

RESUMO

BACKGROUND: The aim of this study was to investigate the effectiveness of a Computer-based Cognitive Behavioral Therapy (CCBT) and identify the characteristics of depressed adolescents that participated in the CCBT program. METHODS: Screening tests for depression and help-seeking variables were conducted in school-aged Korean adolescents (n= 376, mean age=15.71 years, 53.7% female). The number of adolescents that scored above the threshold for mild depression (PHQ-9, CES-D) was 139. Fifty adolescents agreed to participate in the randomized controlled trial (RCT) of CCBT program. Twenty-five adolescents were randomly assigned to the treatment group, and the other 25 to the waitlist control group. The treatment group engaged in CCBT with therapeutic support. To identify variables affecting the outcomes, the quality of their homework compliance also was assessed. RESULTS: Participants (n=50) who agreed to participate in the CCBT program demonstrated different help-seeking attitudes - a greater recognition of the need for help and lower interpersonal openness - compared to the adolescents (n=87) who did not participate (t = -2.93, p < .01; t = 3.50, p < .001). The treatment group showed significant improvements in depression, self-esteem, and quality of life compared to the waitlist group. Adolescents with high homework compliance showed a significant decrease in the depression scores compared to adolescents with low homework compliance. LIMITATIONS: Small sample size, no follow-up assessments. CONCLUSION: CCBT could be an effective alternative for depressed adolescents, especially those who tend to have low interpersonal openness. To improve the effects of CCBT, therapeutic support needs to be provided.


Assuntos
Terapia Cognitivo-Comportamental , Transtorno Depressivo , Terapia Assistida por Computador , Adolescente , Criança , Computadores , Transtorno Depressivo/terapia , Feminino , Humanos , Masculino , Qualidade de Vida
10.
Biochem Biophys Res Commun ; 542: 9-16, 2021 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-33482471

RESUMO

ß-transducin repeats-containing protein-1 (ß-TrCP1) serves as the substrate recognition subunit for SCFß-TrCP E3 ubiquitin ligases, which specifically ubiquitinate phosphorylated substrates. Three variants of ß-TrCP1 are known and act as homodimer or heterodimer complexes. Here, we identified a novel full-sequenced variant, ß-TrCP1-variant 4, which harbours exon II instead of exon III of variant 1, with no change in the open reading frame. The expression of ß-TrCP1-variant 4 is lower than that of variant 1 or 2 in ovarian cancer cell lines, whereas it is abundantly expressed in normal and cancerous ovarian tissues. Moreover, ß-TrCP1-variant 2 was aberrantly expressed more than variant 1 in ovarian cancer tissues whereas variant 1 was expressed more in normal tissues. Similar to variants 1 and 2, ß-TrCP1-variant 4 directly interacts with ß-catenin, one of the substrates of SCFß-TrCP E3 ubiquitin ligase and down-regulates the transcriptional activity and protein expression of ß-catenin with a significantly weaker effect than that by variants 1 and 2. However, the co-expression of ß-TrCP1-variant 4 with variant 1 in same proportion has no effect, whereas other combinations effectively down-regulate the activity of ß-catenin, indicating that the heterodimer of variants 1 and 4 has no function. Thus, ß-TrCP1-variant 4 could play a critical role in SCFß-TrCP E3 ligase-mediated ubiquitination by acting as a negative regulator of ß-TrCP1-variant 1.

11.
Medicine (Baltimore) ; 100(48): e28005, 2021 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-35049210

RESUMO

ABSTRACT: Nonsteroidal anti-inflammatory drug-induced small bowel injuries (NSIs) have been largely ignored for decades due to the focus on nonsteroidal anti-inflammatory drug gastropathy. With the visualization of the small intestines enabled by video capsule endoscopy, the frequency and severity of NSIs have become more evident. NSIs have a complex pathophysiology, and no effective preventive or treatment options have been proven. Complementary and alternative medicine (CAM) has been used to treat disorders of the small intestine, and more research on its effectiveness for NSIs has been conducted.We reviewed the current evidence and mechanisms of action of CAMs on NSI. Clinical and experimental studies on the effect of CAMs on NSIs were performed using 10 databases.Twenty-two studies (3 clinical and 19 in vivo experimental studies) were included in the final analysis involving 10 kinds of CAMs: bovine colostrum, Orengedokuto (coptis), muscovite, licorice, grape seed, wheat, brown seaweed, Ganoderma lucidum fungus mycelia, Chaenomeles speciosa (sweet) Nakai (muguasantie), and Jinghua Weikang capsule. The mechanisms of CAM include an increase in prostaglandin E2, reparation of the enteric nervous system, inhibition of pro-inflammatory cytokines, reduction of intestinal permeability and enteric bacterial numbers, decrease in oxidative stress, and modulation of small intestinal motility.CAM may be a novel alternative option for treating and preventing NSI, and further studies on human and animal models with relevant comorbidities are warranted.


Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Terapias Complementares/métodos , Intestino Delgado/efeitos dos fármacos , Intestino Delgado/lesões , Animais , Bovinos , Humanos , Intestinos
12.
Exp Mol Med ; 52(8): 1255-1263, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32859954

RESUMO

T cells are the central mediators of both humoral and cellular adaptive immune responses. Highly specific receptor-mediated clonal selection and expansion of T cells assure antigen-specific immunity. In addition, encounters with cognate antigens generate immunological memory, the capacity for long-term, antigen-specific immunity against previously encountered pathogens. However, T-cell receptor (TCR)-independent activation, termed "bystander activation", has also been found. Bystander-activated T cells can respond rapidly and secrete effector cytokines even in the absence of antigen stimulation. Recent studies have rehighlighted the importance of antigen-independent bystander activation of CD4+ T cells in infection clearance and autoimmune pathogenesis, suggesting the existence of a distinct innate-like immunological function performed by conventional T cells. In this review, we discuss the inflammatory mediators that activate bystander CD4+ T cells and the potential physiological roles of these cells during infection, autoimmunity, and cancer.


Assuntos
Imunidade Adaptativa , Efeito Espectador/imunologia , Linfócitos T CD4-Positivos/imunologia , Imunidade Inata , Animais , Citocinas/metabolismo , Humanos , Ativação Linfocitária/imunologia
13.
Psychiatry Investig ; 16(10): 728-736, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31550876

RESUMO

OBJECTIVE: Many depressed adolescents do not seek professional help despite there being evidence-based treatments for depression, such as cognitive behavioral therapy or computer-based therapy. To increase professional help-seeking behavior in depressed adolescents, it is necessary to positively change help-seeking attitudes. This study aimed to explore the effect of sub-groups of help-seeking attitudes, gender, and depression level on adolescents' help-seeking intentions and their perceptions of computer-based psychotherapy. METHODS: Participants were 246 adolescents aged 13-18 years recruited from six middle and high schools in South Korea. Measures were self-administered questionnaires, and included the Patient Health Questionnaire-9, the Attitudes Toward Seeking Professional Psychological Help Scale, the Intention to Seek Counseling Inventory, Preferences for Depression Treatment, and the Perceptions of Computerized Therapy Questionnaire. RESULTS: Help-seeking intentions were positively related with female gender and the recognition of the need for help. A higher level of confidence in therapists was related to high preference for computer-based therapy and face-to-face therapy. Adolescents with more severe depression were more likely to prefer pharmacotherapy. The perceptions of computer-based therapy were more positive in male adolescents, and in adolescents with a higher level of confidence in therapists yet a lower level of interpersonal openness. CONCLUSION: To promote adolescents' help-seeking behavior, improvement of the recognition of the need for help is required, especially among male adolescents. Computer-based therapy provides an alternative for male adolescents with high confidence in therapists yet low interpersonal openness. Consideration of the help-seeking attitudes and gender is needed when providing therapeutic intervention to depressed adolescents.

14.
Transplant Proc ; 51(8): 2808-2813, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31563248

RESUMO

INTRODUCTION: Prostaglandin E1 (PGE1) administered to patients in the immediate post-transplant period has been known to reduce ischemic reperfusion injuries (IRIs), but the effect on IRI of PGE1 administered to the donor is unknown. The purpose of this study was to determine the effect on IRI of PGE1 injected into donor rats during heterotopic heart transplantation. METHODS: Genetically identical male Sprague Dawley rats with a body weight of 300-320 g at 8-9 weeks of age were used for the study. Experimental methods were the same in the control (G0, n = 6) and experimental groups (G1, n = 6), but only the donor rats in the experimental group received an intramuscular injection of PGE1 (5 µg/kg) prior to the donor surgery. On day 1 the animals were sacrificed with the removal of the transplanted heart. Histologic analysis was performed in the hematoxylin-eosin-stained slides to assess interstitial edema and neutrophil infiltration by a pathologist. RESULTS: Median times of the donor organ procurement, cold ischemia, and warm ischemia were 37, 69, and 35 minutes, respectively, in the G0 group and 38, 76.5, and 33 minutes respectively in G1 group; there were no statistical differences. Heartbeats were observed in the transplanted graft in 2 of the G0 group and 2 of G1 group immediately after heart transplantation, but in all transplanted grafts on day 1 after surgery. Histologic scores for neutrophil infiltration showed significantly lower in the G1 group than in the G0 group. CONCLUSION: PGE1 administration to donors in a rat heart transplantation model may significantly reduce IRI.


Assuntos
Alprostadil/uso terapêutico , Transplante de Coração/efeitos adversos , Traumatismo por Reperfusão/prevenção & controle , Vasodilatadores/uso terapêutico , Alprostadil/administração & dosagem , Animais , Masculino , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/etiologia , Doadores de Tecidos , Transplante Heterotópico , Vasodilatadores/administração & dosagem
15.
J Vasc Access ; 20(6): 646-651, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30919734

RESUMO

BACKGROUND: Preoperative mapping with duplex ultrasonography is crucial for successful vascular access creation for hemodialysis. The aims of this study are to assess the baseline characteristics of arm vessels by preoperative duplex ultrasonography in Korean patients, to find out a preoperative duplex ultrasonography parameter precluding distal arteriovenous fistula creation, to assess the maturation failure rate of arteriovenous fistulas, and to identify associated risk factors. METHODS: Preoperative duplex ultrasonography mapping for vascular access creation was done in all patients with end-stage renal diseases during the year 2015. The baseline data of duplex ultrasonography were retrospectively analyzed with follow-up clinical data. RESULTS: A total of 299 end-stage renal disease patients (mean age = 62 years, 62% male) were included. On preoperative duplex ultrasonography, mean diameters of radial artery and cephalic vein at wrist were 2.03 and 2.40 mm in the non-dominant arm and 2.10 and 2.26 mm in the dominant arm, respectively. The most common reason for precluding radial-cephalic arteriovenous fistula at wrist was small-sized cephalic vein. Multivariate logistic regression analysis revealed that the risk factors for inadequate vessels were warfarin treatment, old age (⩾75 years), and peripheral arterial occlusive disease. The rate of arteriovenous fistula maturation failure was 21% and vein diameter <2.5 mm was the only risk factor for arteriovenous fistula maturation failure by multivariate logistic regression analysis. CONCLUSION: Preoperative duplex ultrasonography evaluation is important to find out inadequate vessels for native arteriovenous fistula and to determine the location of vascular access.


Assuntos
Derivação Arteriovenosa Cirúrgica , Falência Renal Crônica/terapia , Artéria Radial/diagnóstico por imagem , Diálise Renal , Ultrassonografia Doppler , Extremidade Superior/irrigação sanguínea , Veias/diagnóstico por imagem , Idoso , Derivação Arteriovenosa Cirúrgica/efeitos adversos , Feminino , Humanos , Falência Renal Crônica/diagnóstico por imagem , Falência Renal Crônica/fisiopatologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Artéria Radial/fisiopatologia , Artéria Radial/cirurgia , Fluxo Sanguíneo Regional , Estudos Retrospectivos , Fatores de Risco , Seul , Falha de Tratamento , Grau de Desobstrução Vascular , Veias/fisiopatologia , Veias/cirurgia
16.
Biochem Biophys Res Commun ; 509(1): 167-174, 2019 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-30579607

RESUMO

PURPOSE: Although Mycobacterium bovis Bacillus Calmette-Guérin (BCG) is the most widely used bladder cancer immunotherapy, innate immune responses involving antimicrobial peptides (AMPs) cause BCG failure and unwanted side effects. Here, we generated genetically modified BCG strains with improved immunotherapeutic effects by adding genes that confer evasion of AMPs. MATERIALS AND METHODS: We constructed recombinant BCG (rBCG) strains expressing Streptococcal inhibitor of complement (Sic), which confers resistance to human α-defensin-1 and cathelicidin, and d-alanyl carrier protein ligase (dltA), which confers resistance to cationic AMPs. Sic and dltA were separately cloned into the pMV306 plasmid and introduced into BCG via electroporation. Then, the efficacy of the rBCGs was tested in a growth inhibition assay using two bladder cancer cell lines (5637, T24). RESULTS: We confirmed the presence of cDNA segments corresponding to the Sic and dltA genes in total mRNA of the rBCG strains containing Sic (rBCG-Sic) and dltA (rBCG-dltA), and these rBCGs showed higher survival against AMPs. The growth inhibitory effects of rBCGs on bladder cancer cells were significantly enhanced compared to those of the parent BCG, and THP-1 migration also increased. After 8 h of infection, the levels of internalization were higher in rBCG-infected bladder cancer cells than in BCG-infected cells, and cells infected with rBCGs showed increased release of antitumor cytokines, such as IL-6/12, TNF-α, and INF-γ, resulting in inhibition of bacterial killing and immune modulation via antimicrobial peptides. CONCLUSIONS: rBCG-Sic and rBCG-dltA can effectively evade BCG-stimulated AMPs, and may be significantly improved immunotherapeutic tools to treat bladder cancer.


Assuntos
Peptídeos Catiônicos Antimicrobianos/imunologia , Vacina BCG/genética , Vacinas Anticâncer/genética , Mycobacterium bovis/genética , Neoplasias da Bexiga Urinária/terapia , Vacina BCG/imunologia , Vacina BCG/farmacologia , Vacinas Anticâncer/imunologia , Vacinas Anticâncer/farmacologia , Linhagem Celular Tumoral , Humanos , Imunidade Inata , Imunoterapia/métodos , Mycobacterium bovis/imunologia , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/farmacologia , Neoplasias da Bexiga Urinária/imunologia , Neoplasias da Bexiga Urinária/patologia , Vacinas Sintéticas/genética , Vacinas Sintéticas/imunologia , Vacinas Sintéticas/farmacologia
17.
Oncotarget ; 8(58): 97990-98003, 2017 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-29228668

RESUMO

Colony stimulating factor 1 receptor (CSF-1R) regulates the monocyte/macrophage system, which is an essential component of cancer development. Therefore, CSF-1R might be an effective target for anti-cancer therapy. The overexpression of transforming growth factor (TGF)-ß stimulated clone-22 (TSC-22) inhibits cancer cell proliferation and induces apoptosis, and TSC-22 is emerging as a key factor in tumorigenesis. In this study, we discovered CSF-1R as a new interacting partner of TSC-22 and identified its elevated expression in cervical cancer cells. In particular, we found that TSC-22 interacted with the intracellular tyrosine kinase insert domain (539-749) of CSF-1R, which activates the AKT and ERK signaling pathways. This binding blocked AKT and ERK signaling, thereby suppressing the transcriptional activity of NF-κB. The overexpression of TSC-22 significantly decreased CSF-1R protein levels, affecting their autocrine loop. TSC-22 injected into a xenograft mouse model of human cervical cancer markedly inhibited tumor growth. The reduction of CSF-1R protein significantly suppresses cervical cancer cell proliferation and motility and induces apoptotic cell death. This association between TSC-22 and CSF-1R could be used as a novel therapeutic target and prognostic marker for cervical cancer.

18.
Trials ; 18(1): 439, 2017 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-28938905

RESUMO

BACKGROUND: Sarpogrelate is expected to reduce restenosis by protecting blood vessels from oxidative stress and vascular endothelial dysfunction as well as by acting as an antiplatelet agent after endovascular treatment (EVT). This trial was designed to compare aspirin plus sustained-release (SR) sarpogrelate with aspirin plus clopidogrel for the prevention of restenosis in patients with femoro-popliteal (FP) peripheral artery disease (PAD) who underwent EVT. METHODS/DESIGN: This is an open label, multicenter, prospective randomized controlled clinical trial. Patients will be eligible for inclusion in this study if they require EVT for stenosis or occlusion of a de novo FP lesion. Patients in each group will receive aspirin 100 mg with clopidogrel 75 mg or aspirin 100 mg with SR sarpogrelate 300 mg (Anplone®) orally once a day for six months. The primary outcome of the study is the restenosis rate, defined as > 50% luminal reduction by computed tomography angiography or catheter angiography in the six-month follow-up period. Secondary outcomes include target lesion revascularization, major bleeding, ipsilateral major amputation, all-cause mortality, and all adverse events that take place in those six months. DISCUSSION: This study is a multicenter randomized controlled trial designed to show non-inferiority in terms of the re-stenosis rate of SR sarpogrelate compared to clopidogrel for EVT for PAD in FP lesion patients. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02959606 . Registered on 9 November 2016.


Assuntos
Procedimentos Endovasculares , Artéria Femoral/efeitos dos fármacos , Doença Arterial Periférica/terapia , Inibidores da Agregação Plaquetária/uso terapêutico , Artéria Poplítea/efeitos dos fármacos , Succinatos/uso terapêutico , Amputação Cirúrgica , Aspirina/uso terapêutico , Protocolos Clínicos , Clopidogrel , Angiografia por Tomografia Computadorizada , Constrição Patológica , Quimioterapia Combinada , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/mortalidade , Artéria Femoral/diagnóstico por imagem , Artéria Femoral/fisiopatologia , Hemorragia/induzido quimicamente , Humanos , Salvamento de Membro , Doença Arterial Periférica/diagnóstico por imagem , Doença Arterial Periférica/mortalidade , Doença Arterial Periférica/fisiopatologia , Inibidores da Agregação Plaquetária/efeitos adversos , Artéria Poplítea/diagnóstico por imagem , Artéria Poplítea/fisiopatologia , Estudos Prospectivos , Recidiva , República da Coreia , Projetos de Pesquisa , Fatores de Risco , Succinatos/efeitos adversos , Ticlopidina/análogos & derivados , Ticlopidina/uso terapêutico , Fatores de Tempo , Resultado do Tratamento , Grau de Desobstrução Vascular/efeitos dos fármacos
19.
Vasc Specialist Int ; 33(2): 81-83, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28691000

RESUMO

Endovascular abdominal aortic aneurysm (AAA) repair has been widely used for the treatment of AAA as a safe and efficient method, but endoleaks causing persistent expansion of aneurysm sac may cause aneurysmal rupture and death. Type 3 endoleak is rare but a predominant cause of late rupture. Type 3b endoleak can be misdiagnosed as type 2 endoleak, which is more frequent. Here we report two cases of type 3b endoleak mimicking type 2 endoleak, which were successfully treated by open surgery of partial explantation of the stent-graft and endoaneurysmal interposition graft replacement.

20.
Vasc Specialist Int ; 33(1): 33-36, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28377910

RESUMO

A 71-year-old woman presented with an enlarging mass in the right buttock, with pain and tingling sensation in sitting position. Five years ago, she was diagnosed with acute limb ischemia due to acute thrombosis of right persistent sciatic artery (PSA), and she underwent successful thromboembolectomy and femoro-tibioperoneal trunk bypass. Computed tomography angiography revealed a huge PSA aneurysm (PSAA). During the previous bypass, the distal popliteal artery was ligated just above the distal anastomosis to exclude the PSAA, whose proximal end was already thrombosed. However, PSAA has grown to cause compression symptoms, and the mechanism of aneurysm growth can be ascribed to type 1a or type 2 endoleak. In order to relieve the compression symptoms, aneurysm excision was performed without any injury to the sciatic nerve. A postoperative tingling sensation due to sciatic-nerve stimulation in the supine position resolved spontaneously one month after surgery.

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