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1.
Transl Stroke Res ; 2020 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-32472251

RESUMO

We investigated the effectiveness of adding antiplatelet (AP) to oral anticoagulant (OAC) treatment versus OAC treatment alone in patients with AIS with atrial fibrillation (AF) and significant large artery steno-occlusion (LASO). This study is a retrospective analysis of a nationwide, prospective, multicenter stroke registry between April 2008 and November 2017. Patients with acute (within 48 h of onset) and mild-to-moderate (NIHSS score ≤ 15) stroke with AF and concomitant LASO were identified. Antithrombotic regimens at discharge were categorized into OAC alone or OAC + AP. The primary outcome event was a composite of recurrent stroke, myocardial infarction, and all-cause mortality within 3 months of stroke. Among the 2553 patients (age, 73 ± 10 years; men, 50.4%), 78.8% were treated with OAC alone, and 21.2% were treated with OAC + AP. The primary outcome events were significantly more common in the OAC + AP group (6.7%) than the OAC alone group (4.3%) (p = 0.02). Weighted Cox proportional hazard analysis showed that OAC + AP increased the risk of 3-month primary outcome events compared with OAC alone (HR, 1.62 [1.06 to 2.46]). A potential interaction between the type of LASO and discharge antithrombotics was suggested (Pinteraction = 0.04); unlike in patients with complete occlusion (OAC + AP; HR, 2.00 [1.27-3.15]), OAC + AP was comparable with OAC alone for 3-month primary outcome in patients with moderate-to-severe stenosis (HR, 0.54 [0.17-1.70]). In conclusion, OAC + AP might increase the risk of 3-month outcome events compared with OAC alone in patients with AIS with AF and concomitant LASO. However, the effect of additional AP to OAC might differ according to LASO type.

2.
Asia Pac J Public Health ; : 1010539520920524, 2020 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-32468824

RESUMO

This study aimed to estimate the socioeconomic burden of asthma in South Korea. The data were obtained from the National Patient Sample of 2014. The direct costs included health care and non-health care costs, and the indirect costs included loss of productivity. To estimate the prevalence of asthma, this study used both primary diagnoses and treatment-based criteria. The prevalence of asthma was 3.7% using primary diagnosis-based criteria. The total costs of asthma were $645.8 million. The direct and indirect costs were $553.9 million and $92.0 million, respectively. When the treatment-based criteria were applied, the prevalence decreased to 1.8% and the total costs decreased to $465.1 million. The direct and indirect costs were $394.9 million and $70.2 million, respectively. In the future, the cost of asthma, derived from various perspectives, should be regularly estimated and used as a basis for lowering the burden of disease due to asthma.

3.
Hand (N Y) ; : 1558944720919183, 2020 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-32447986

RESUMO

Background: Although cases of impaired long bone growth due to bone and joint infections in childhood are sometimes reported, few cases of growth impairment of the ulna due to septic osteomyelitis have been described. We report herein a case of ulnar partial physeal arrest treated using the Langenskiöld procedure. Materials and Methods: A boy developed septic osteomyelitis of the right distal ulna at age 2 years 6 months. Osteomyelitis subsided after antibiotic treatment and external immobilization. As a result of impaired growth of the ulna along the long axis, shortening and trumpet-shaped deformity of the metaphysis gradually appeared. Computed tomography revealed a bony bridge, and premature epiphyseal closure due to osteomyelitis was diagnosed. The Langenskiöld procedure was performed at 4 years 4 months old. Results: As of 2 years 9 months later, no further ulnar shortening has occurred and morphological remodeling has been confirmed. Conclusions: The treatments employed for ulnar shortening include ulnar lengthening by callotasis as well as stapling of the distal radial epiphyseal line or radial shortening osteotomy. In this case, the Langenskiöld procedure proved effective because the patient was still young with growth potential and the area of the bony bridge after osteomyelitis-induced epiphyseal line damage was <30%.

4.
Phytochemistry ; 176: 112400, 2020 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-32408189

RESUMO

Adulterants in processed food and herbal medicines reduce their safety, quality control, or pharmacological efficacy. Four mistletoe species, including Viscum coloratum, inhabit Korea. Leaves and branches of V. coloratum, defined as edible or medicinal mistletoe species in Korean, are used to prepare Korean herbal medicines as well as leached tea. However, other mistletoe species including Taxillus sutchuenensis var. duclouxii, Korthalsella japonica, and Loranthus tanakae are frequently distributed as authentic V. coloratum in Korean markets because of similarities in the branches morphology and Korean names of these species with V. coloratum. Although herbal medicines and food products prepared from the other mistletoe species are inauthentic, they are sold at high prices because of the rarity of these species. Thus, it is important to distinguish between authentic and inauthentic adulterant mistletoe species. In this study, we developed species-specific primer, based on matK sequences, suitable for both conventional PCR and real time PCR (qPCR) assay. These assays allowed rapid discrimination among all four mistletoe species. Moreover, qPCR assay enabled the detection of trace amounts of adulterant mistletoe species in V. coloratum samples. Furthermore, we used these assays to monitor commercial mistletoe products distributed in Korean markets. Our data suggest that these methods would serve as a reliable genetic tool to prevent adulteration and standardize the quality of commercial V. coloratum products.

5.
Sci Rep ; 10(1): 6270, 2020 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-32286437

RESUMO

The Oxford classification was developed to predict the outcome of IgA nephropathy (IgAN). Based on the upper reference limit (95th percentile) for the number of globally sclerotic glomeruli (GSG) expected on biopsy according to age, we evaluated whether the prognosis of IgAN was affected by the age-calibrated numbers of GSG independent of the Oxford classification. Patients diagnosed with IgAN on renal biopsy in a single center from January 2011 to December 2018 were analyzed retrospectively. Patients with more GSG number than the upper reference limit expected on biopsy according to age were categorized in a group of GSG abnormal for age. We analyzed in two ways, calculating the median rate of decline in estimated glomerular filtration rate (eGFR) and time-to-event defined as a decline of eGFR level to 40% lower than the baseline. There were 111 patients in the group of GSG abnormal for age. In this group, the rate of eGFR decline was faster by 1.85 (3.68-0.03) ml/min/1.73 m2 per year in the fully-adjusted robust regression model. The adjusted hazard ratio for eGFR decline for renal outcome was 29.10 (2.18-388.49). The cumulative incidence of CKD progression was significantly higher, especially for those with T score of 0 in the Oxford classification. We suggest that GSG abnormal for age is an independent risk factor in predicting the renal outcome of IgAN.

6.
Neurology ; 94(19): e1984-e1995, 2020 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-32273430

RESUMO

OBJECTIVE: It is uncertain whether patients with cardioembolic stroke and without a guidance-based indication for statin therapy should be administered a statin for prevention of subsequent vascular events. This study was performed to determine whether the statin therapy is beneficial in preventing major vascular events in this population. METHODS: Using a prospective multicenter stroke registry database, we identified patients with acute cardioembolic stroke who were hospitalized between 2008 and 2015. Patients who had other established indications for statin therapy according to current guidelines were excluded. Major vascular event was defined as a composite of stroke recurrence, myocardial infarction, and vascular death. We performed frailty model analysis with the robust sandwich variance estimator using the stabilized inverse probability of treatment weighting method to estimate hazard ratios of statin therapy on outcomes. RESULTS: Of 6,124 patients with cardioembolic stroke, 2,888 (male 44.6%, mean age 75.3 years, 95% confidence interval [CI] 74.8-75.8) were eligible, and 1,863 (64.5%) were on statin therapy during hospitalization. After a median follow-up of 359 days, cumulative incidences of major vascular events were 9.3% in the statin users and 20.5% in the nonusers (p < 0.001 by log-rank test). The adjusted hazard ratios of statin therapy were 0.39 (95% CI 0.31-0.48) for major vascular events, 0.81 (95% CI 0.57-1.16) for stroke recurrence, 0.28 (95% CI 0.21-0.36) for vascular death, and 0.53 (95% CI 0.45-0.61) for all-cause death. CONCLUSION: Starting statin during the acute stage of ischemic stroke may reduce the risk of major vascular events, vascular death, and all-cause death in patients with cardioembolic stroke with no guidance-based indication for statin.

7.
Carbohydr Polym ; 237: 116161, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32241446

RESUMO

Obesity, a major risk factor for type 2 diabetes and cardiovascular diseases, is characterized by an abnormal expansion of adipose tissue. Herein, we investigated the potential of hyaluronic acid nanoparticles (HA-NPs) as therapeutics to treat obesity-related diseases by assessing the in vitro and in vivo effects of HA-NPs on adipogenesis and lipogenesis. Treatment of 3T3-L1 preadipocytes with HA-NPs resulted in a dose-dependent suppression of adipogenesis and lipid accumulation, and decreased the expression of key adipogenic and lipogenic regulators. However, these HA-NPs mediated effects were not observed in 3T3-L1 cells transfected with siRNAs against CD44, a major HA receptor. Further, HA-NP treatment of diet-induced obese (DIO) mice reduced the epididymal fat mass and suppressed the induction of adipogenic and lipogenic regulators, while these effects were attenuated in the CD44-null mice. Thus, our study provides a better understanding of how HA-NP modulates fat accumulation and presents a potential anti-obesity strategy targeting CD44.

8.
Molecules ; 25(7)2020 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-32224956

RESUMO

By simple soaking titanium dioxide (TiO2) films in an aqueous Na2S solution, we could prepare surface-modified photoanodes for application to dye-sensitized solar cells (DSSCs). An improvement in both the open-circuit voltage (Voc) and the fill factor (FF) was observed in the DSSC with the 5 min-soaked photoanode, compared with those of the control cell without any modification. The UV-visible absorbance spectra, UPS valence band spectra, and dark current measurements revealed that the Na2S modification led to the formation of anions on the TiO2 surface, and thereby shifted the conduction band edge of TiO2 in the negative (upward) direction, inducing an increase of 29 mV in the Voc. It was also found that the increased FF value in the surface-treated device was attributed to an elevation in the shunt resistance.

9.
Biomaterials ; 245: 119974, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32220799

RESUMO

Despite being crucial for combating microbes, paradoxical Toll-like receptors (TLRs) signaling have been associated with the aggravation of multiple immune disorders such as systemic lupus erythematosus, psoriasis, rheumatoid arthritis, and nonalcoholic steatohepatitis. The stoichiometry and precise arrangement of the interaction of adapters (via their Toll/interleukin-1 receptor [TIR] domains) are indispensable for the activation of TLRs and of downstream signaling cascades. Among adapters, plasma membrane-anchored MyD88 adaptor-like (MAL) has the potential for BB-loop-mediated self-oligomerization and interacts with other TIR domain-containing adaptors through αC and αD helices. Here, we used information on the MAL-αC interface to exploit its pharmacophores and to design a decoy peptide (MIP2) with broad-range TLR-inhibitory abilities. MIP2 abrogated MyD88- and TRIF-dependent lipopolysaccharide (LPS)-induced TLR4 signaling in murine and human cell lines and manifested a therapeutic potential in models of psoriasis, systemic lupus erythematosus, nonalcoholic steatohepatitis, and sepsis. Levels of hallmark serological and histological biomarkers were significantly restored and the disease symptoms were substantially ameliorated by MIP2 treatment of the animals. Collectively, our biophysical, in vitro, and in vivo findings suggest that MIP2 has broad specificity for TLRs and may be effective in modulating autoimmune complications caused by microbial or environmental factors.

10.
Surg Endosc ; 2020 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-32144557

RESUMO

BACKGROUND: Laparoscopic distal gastrectomy for early gastric cancer has been widely accepted, but laparoscopic total gastrectomy has still not gained popularity because of technical difficulty and unsolved safety issue. We conducted a single-arm multicenter phase II clinical trial to evaluate the safety and the feasibility of laparoscopic total gastrectomy for clinical stage I proximal gastric cancer in terms of postoperative morbidity and mortality in Korea. The secondary endpoint of this trial was comparison of surgical outcomes among the groups that received different methods of esophagojejunostomy (EJ). METHODS: The 160 patients of the full analysis set group were divided into three groups according to the method of EJ, the extracorporeal circular stapling group (EC; n = 45), the intracorporeal circular stapling group (IC; n = 64), and the intracorporeal linear stapling group (IL; n = 51). The clinicopathologic characteristics and the surgical outcomes were compared among these three groups. RESULTS: There were no significant differences in the early complication rates among the three groups (26.7% vs. 18.8% vs. 17.6%, EC vs. IC vs. IL; p = 0.516). The length of mini-laparotomy incision was significantly longer in the EC group than in the IC or IL group. The anastomosis time was significantly shorter in the EC group than in the IL group. The time to first flatus was significantly shorter in the IL group than in the EC group. The long-term complication rate was not significantly different among the three groups (4.4% vs. 12.7% vs. 7.8%; EC vs. IC vs. IL; p = 0.359), however, the long-term incidence of EJ stenosis in IC group (10.9%) was significantly higher than in EC (0%) and IL (2.0%) groups (p = 0.020). CONCLUSIONS: The extracorporeal circular stapling and the intracorporeal linear stapling were safe and feasible in laparoscopic total gastrectomy, however, intracorporeal circular stapling increased EJ stenosis.

11.
Medicine (Baltimore) ; 99(12): e19525, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32195955

RESUMO

BACKGROUND: To assess the arterial oxygen partial pressure (PaO2) at defined time points during preoxygenation and to compare high-flow heated humidified nasal oxygenation with standard preoxygenation using oxygen insufflation via a facemask for at least 5 minutes, before intubation during induction of general anesthesia. METHODS: This randomized, single-blinded, prospective study will be conducted in patients undergoing head and neck surgery. After standard monitoring, the artery catheter at the radial artery or dorsalis pedis artery will be placed and arterial blood gas analysis (ABGA) for baseline values will be performed simultaneously. Each group will be subjected to 1 of 2 preoxygenation methods (high-flow nasal cannula or simple facemask) for 5 minutes, and ABGA will be performed twice. After confirming intubation, we will start mechanical ventilation and check the vital signs and perform the final ABGA. DISCUSSION: This trial aims to examine the trajectory of PaO2 levels during the whole preoxygenation procedure and after intubation. We hypothesize that preoxygenation with the high-flow nasal cannula will be superior to that with the face mask. STUDY REGISTRATION: This trial was registered with the Clinical Trial Registry (NCT03896906; ClinicalTrials.gov).


Assuntos
Anestesia Geral/tendências , Monitorização Transcutânea dos Gases Sanguíneos/métodos , Cabeça/cirurgia , Oxigenação Hiperbárica/tendências , Pescoço/cirurgia , Gasometria , Cânula/normas , Cânula/estatística & dados numéricos , Humanos , Intubação Intratraqueal/métodos , Máscaras/normas , Máscaras/estatística & dados numéricos , Ventilação não Invasiva/instrumentação , Ventilação não Invasiva/métodos , Oxigênio/sangue , Estudos Prospectivos , Artéria Radial/cirurgia , Respiração Artificial/instrumentação , Respiração Artificial/métodos , Dispositivos de Acesso Vascular/normas
12.
Neurology ; 94(9): e978-e991, 2020 03 03.
Artigo em Inglês | MEDLINE | ID: mdl-32029544

RESUMO

OBJECTIVE: Stroke is a devastating and costly disease; however, there is a paucity of information on long-term costs and on how they differ according to 3-month modified Rankin scale (mRS) score, which is a primary outcome variable in acute stroke intervention trials. METHODS: We analyzed a prospective multicenter stroke registry (Clinical Research Collaboration for Stroke in Korea) database through linkage with claims data from the National Health Insurance Service with follow-up to December 2016. Healthcare expenditures were converted into daily cost individually, and annual and cumulative costs up to 5 years were estimated and compared according to the 3-month mRS score. RESULTS: Between January 2011 and November 2013, 11,136 patients were enrolled in the study. The mean age was 68 years, and 58% were men. The median follow-up period was 3.9 years (range 0-5 years). Mean cumulative cost over 5 years was $117,576 (US dollars [USD]); the cost in the first year after stroke was the highest ($38,152 USD), which increased markedly from the cost a year before stroke ($8,718 USD). The mean 5-year cumulative costs differed significantly according to the 3-month mRS score (p < 0.001); the costs for a 3-month mRS score of 0 or 5 were $53,578 and $257,486 USD, respectively. Three-month mRS score was an independent determinant of long-term costs after stroke. CONCLUSIONS: We show that 3-month mRS score plays an important role in the prediction of long-term costs after stroke. Such estimates relating to 3-month mRS categories may be valuable when undertaking health economic evaluations related to stroke care.

13.
Sci Rep ; 10(1): 1716, 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32015422

RESUMO

Although angiotensin receptor blockers (ARBs) are considered as an alternative for those with angiotensin converting enzyme inhibitors (ACEi) intolerance, the comparative effectiveness of ARBs and ACEi remains controversial in patients who underwent coronary artery bypass grafting (CABG). We aimed to compare the clinical effects of the two types of renin-angiotensin-aldosterone system (RAAS) inhibitors in patients who underwent CABG. From January 2001 to January 2015, among the 5456 patients, data from 1198 (20.1%) patients who used a RAAS inhibitor at discharge were analyzed. These 1198 patients were classified into ACEi (N = 900) and ARB (N = 298) groups. The primary outcome was major adverse cardiovascular and cerebrovascular events (MACCE) during a median follow-up period of 48 months. Propensity-matched analysis revealed that the incidence of MACCE over a 48 month follow-up period did not differ between the groups (HR, 0.65; 95% CI, 0.36-1.21; p = 0.17), but it was significantly lower in the ARB group during the 12 month follow-up period (HR, 0.46; 95% CI, 0.22-0.96; p = 0.04). In conclusion, ARBs may have comparable protective effects to ACEi and be a reasonable alternative for intolerant patients after CABG. The beneficial effects of ARBs depending on follow-up period require further investigation.

14.
Stroke ; 51(4): 1309-1312, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32078481

RESUMO

Background and Purpose- We evaluated whether hemoglobin concentration at admission was associated with stroke recurrence and composite vascular events (stroke, myocardial infarction, and vascular death) in acute ischemic stroke. Methods- We collected data from patients with acute ischemic stroke or transient ischemic attack from a multicenter stroke registry database in Korea. The association of hemoglobin concentration with 1-year stroke recurrence and composite vascular events was evaluated with respect to age, presence of cerebral artery stenosis, stroke severity, and stroke subtype. Results- Hemoglobin levels were inversely associated with stroke recurrence and composite vascular events. One-year rates of stroke recurrence and composite vascular events were significantly higher in patients with anemia or moderate anemia. In multivariable analyses, moderate anemia remained an independent predictor of stroke recurrence (adjusted hazard ratio, 1.43 [95% CI, 1.16-1.75]) and composite vascular events (adjusted hazard ratio, 1.26 [95% CI, 1.07-1.48]). Moderate anemia increased the risk of composite vascular events in patients with mild-to-moderate stroke severity (National Institutes of Health Stroke Scale score <16, P=0.01 for interaction). Conclusions- Hemoglobin concentration could be an independent predictor of stroke recurrence and composite vascular events.

15.
EBioMedicine ; 52: 102645, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32014819

RESUMO

BACKGROUND: TLRs are some of the actively pursued drug-targets in immune disorders. Owing to a recent surge in the cognizance of TLR structural biology and signalling pathways, numerous therapeutic modulators, ranging from low-molecular-weight organic compounds to polypeptides and nucleic acid agents have been developed. METHODS: A penetratin-conjugated small peptide (TIP3), derived from the core ß-sheet of TIRAP, was evaluated in vitro by monitoring the TLR-mediated cytokine induction and quantifying the protein expression using western blot. The therapeutic potential of TIP3 was further evaluated in TLR-dependent in vivo disease models. FINDINGS: TIP3 blocks the TLR4-mediated cytokine production through both the MyD88- and TRIF-dependent pathways. A similar inhibitory-effect was exhibited for TLR3 but not on other TLRs. A profound therapeutic effect was observed in vivo, where TIP3 successfully alleviated the inflammatory response in mice model of collagen-induced arthritis and ameliorated the disease symptoms in psoriasis and SLE models. INTERPRETATION: Our data suggest that TIP3 may be a potential lead candidate for the development of effective therapeutics against TLR-mediated autoimmune disorders. FUNDING: This work was supported by the National Research Foundation of Korea (NRF-2019M3A9A8065098, 2019M3D1A1078940 and 2019R1A6A1A11051471). The funders did not have any role in the design of the present study, data collection, data analysis, interpretation, or the writing of the manuscript.

16.
Nat Commun ; 11(1): 107, 2020 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-31919364

RESUMO

Bacteria commonly form dense biofilms encased in extracellular polymeric substances (EPS). Biofilms are often extremely tolerant to antimicrobials but their reliance on shared EPS may also be a weakness as social evolution theory predicts that inhibiting shared traits can select against resistance. Here we show that EPS of Salmonella biofilms is a cooperative trait whose benefit is shared among cells, and that EPS inhibition reduces both cell attachment and antimicrobial tolerance. We then compare an EPS inhibitor to conventional antimicrobials in an evolutionary experiment. While resistance against conventional antimicrobials rapidly evolves, we see no evolution of resistance to EPS inhibition. We further show that a resistant strain is outcompeted by a susceptible strain under EPS inhibitor treatment, explaining why resistance does not evolve. Our work suggests that targeting cooperative traits is a viable solution to the problem of antimicrobial resistance.


Assuntos
Antibacterianos/farmacologia , Biofilmes/crescimento & desenvolvimento , Matriz Extracelular de Substâncias Poliméricas/metabolismo , Imidazóis/farmacologia , Salmonella typhimurium/crescimento & desenvolvimento , Farmacorresistência Bacteriana/genética , Farmacorresistência Bacteriana/fisiologia , Matriz Extracelular de Substâncias Poliméricas/efeitos dos fármacos , Salmonella typhimurium/genética
17.
J Ethnopharmacol ; 252: 112574, 2020 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-31953199

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Mantidis Oötheca (mantis egg case; sangpiaoxiao) is a medicine from an insect source, which has been widely used in Asian countries. However, misidentification due to a lack of information given variations in the medicinal portion of the ootheca and morphological similarities of the ootheca as an egg chamber. AIM OF THE STUDY: Thus, this study aims to provide the first comprehensive data for discriminating authentic of Mantidis Oötheca. Here, we provide detailed ootheca morphology and their molecular information to accurately identify Mantidis Oötheca. MATERIALS AND METHODS: Oothecae of Tenodera angustipennis (Saussure, 1869), Tenodera sinensis (Saussure, 1871), Hierodula patellifera Serville, 1839, and Hierodula sp. were used in the comparative morphological, principal component analysis, and DNA barcoding. RESULTS: The morphological analyses revealed that the emergence area, outline, angle of distal end, width of air-filled layer, and weight are useful diagnostic characters. Using these quantitative and qualitative characteristics, we developed the effective identification key. Furthermore, our CO1 sequences from all individuals were monophyletic with high bootstrap values at genus and species levels. Moreover, morphological identification using our developed key among all studied individuals agreed with molecular identification results using CO1 barcoding data. CONCLUSIONS: These multilateral approaches, including morphological, statistical, and DNA barcoding methods are highly reliable identification tools. Moreover, our diagnostic key characteristics and molecular barcoding should aid in the accurate identification, authentication, and quality control of Mantidis Oötheca medicinal materials.

18.
Anticancer Res ; 40(1): 341-347, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31892585

RESUMO

BACKGROUND/AIM: The prognostic significance of biomarkers related to gastric cancer prognosis has not been fully elucidated. The aim of study was to use immunohistochemical biomarkers to reveal prognosis. PATIENTS AND METHODS: A total of 682 patients who had undergone curative surgery were evaluated regarding the correlation of prognosis and immunohistochemical biomarkers. RESULTS: The COX2-positive groups showed a poor 5-year overall and disease-free survival. Further analysis revealed that COX2 positivity was a significant risk factor for poorer disease-free survival in the group with clinical stage I disease (p=0.016). We also noted a marked trend between COX2 positivity and poorer overall survival. The COX2-positive group showed general postoperative pathological up-staging compared with the COX2-negative group. CONCLUSION: This study showed the potential of COX2 as a biomarker for gastric cancer prognosis. Preoperative evaluation of COX2 might be a useful tool for generating optimal treatment strategies in patients with clinical stage I gastric cancer.


Assuntos
Biomarcadores Tumorais/metabolismo , Ciclo-Oxigenase 2/metabolismo , Neoplasias Gástricas/enzimologia , Neoplasias Gástricas/patologia , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Análise de Sobrevida
19.
Semin Diagn Pathol ; 37(1): 32-46, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31889602

RESUMO

The spectrum of Epstein-Barr virus (EBV)-positive T and NK-cell lymphoproliferations is broad and ranges from reactive self-limited disorders to neoplastic processes with a fulminant clinical course. EBV plays an important role promoting lymphomagenesis, although the precise mechanisms remain elusive. EBV-positive lymphoproliferative disorders (LPD) are more common in East Asia (China, Japan, Korea and Taiwan), and Latin America suggesting a strong genetic predisposition. The revised 2016 World Health Organization (WHO) lymphoma classification recognizes the following malignant NK- and T-cell lymphomas; extranodal NK/T-cell lymphoma, nasal type (ENKTCL), aggressive NK-cell leukemia (ANKL), and the provisional entity within the group of peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS) "primary EBV-positive nodal T or NK cell lymphoma". Disorders presenting mainly in children and young adults include chronic active EBV infection (CAEBV) - systemic and cutaneous forms - which are not considered malignant disorders but were included in the WHO classification for the first time because of the differential diagnosis with other T- or NK-cell lymphomas. CAEBV, cutaneous form, includes hydroa vacciniforme-like LPD (HV-LPD) and severe mosquito bite allergy (SMBA). Finally, systemic EBV-positive T-cell lymphoma of childhood was recognized as lymphoma because of its fulminant clinical course. Given the shared pathogenesis of these disorders, overlapping features are common demanding a close clinical, morphological and molecular correlation for an accurate diagnosis. This review summarizes the clinical, histopathological and molecular features of EBV-associated T and NK-cell LPD, highlighting the main features that might aid in the differential diagnosis.

20.
Arch Toxicol ; 94(2): 427-438, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31912162

RESUMO

Chronic alcohol feeding increases the levels of 2-arachidonoylglycerol (2-AG) in the liver, which activates hepatic cannabinoid receptor type 1 (CB1R), leading to oxidative liver injury. 2-AG biosynthesis is catalyzed by diacylglycerol lipase (DAGL). However, the mechanisms regulating hepatic DAGL gene expression and 2-AG production are largely unknown. In this study, we show that CB1R-induced estrogen-related receptor γ (ERRγ) controls hepatic DAGL gene expression and 2-AG levels. Arachidonyl-2'-chloroethylamide (ACEA), a synthetic CB1R agonist, significantly upregulated ERRγ, DAGLα, and DAGLß, and increased 2-AG levels in the liver (10 mg/kg) and hepatocytes (10 µM) of wild-type (WT) mice. ERRγ overexpression upregulated DAGLα and DAGLß expressions and increased 2-AG levels, whereas ERRγ knockdown abolished ACEA-induced DAGLα, DAGLß, and 2-AG in vitro and in vivo. Promoter assays showed that ERRγ positively regulated DAGLα and DAGLß transcription by binding to the ERR response element in the DAGLα and DAGLß promoters. Chronic alcohol feeding (27.5% of total calories) induced hepatic steatosis and upregulated ERRγ, leading to increased DAGLα, DAGLß, or 2-AG in WT mice, whereas these alcohol-induced effects did not occur in hepatocyte-specific CB1R knockout mice or in those treated with the ERRγ inverse agonist GSK5182 (40 mg/kg in mice and 10 µM in vitro). Taken together, these results indicate that suppression of alcohol-induced DAGLα and DAGLß gene expressions and 2-AG levels by an ERRγ-specific inverse agonist may be a novel and attractive therapeutic approach for the treatment of alcoholic liver disease.

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