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1.
J Korean Med Sci ; 36(14): e90, 2021 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-33847081

RESUMO

BACKGROUND: Liver fibrosis is defined as the accumulation of the extracellular matrix and scar formation. The receptor for advanced glycation end products (RAGE) has been demonstrated to participate in fibrogenesis. S100B is a ligand of RAGE and exerts extracellular functions by inducing a series of signal transduction cascades. However, the involvement of S100B and RAGE in cholestasis-induced liver fibrosis remains unclear. In this study, we investigated S100B and RAGE expression during liver fibrosis in mice that underwent common bile duct ligation (BDL). METHODS: BDL was performed in 10-week-old male C57BL/6J mice with sham control (n = 26) and BDL (n = 26) groups. Expression levels of S100B, RAGE and fibrotic markers in the livers from both groups at week 1 and 3 after BDL were examined by western blot and quantitative real-time reverse transcription polymerase chain reaction analysis. Liver fibrotic changes were examined by histological and ultrastructural analysis. RESULTS: Histological staining with Sirius Red and the evaluation of the messenger RNA expression of fibrotic markers showed noticeable periportal fibrosis and bile duct proliferation. S100B was mainly present in bile duct epithelial cells, and its expression was upregulated in proportion to the ductular reaction during fibrogenesis by BDL. RAGE expression was also increased, and interestingly, triple immunofluorescence staining and transmission electron microscopy showed that both S100B and RAGE were expressed in proliferating bile duct epithelial cells and activated hepatic stellate cells (HSCs) of the BDL livers. In addition, in rat HSCs (HSC-T6), treatment with recombinant S100B protein significantly increased fibrotic markers in a dose-dependent manner, and RAGE small interfering RNA (siRNA) suppressed S100B-stimulated upregulation of fibrotic markers compared with cells treated with scramble siRNA and S100B. CONCLUSION: These findings suggest that the increased expression of S100B and RAGE and the interaction between S100B and RAGE may play an important role in ductular reaction and liver fibrosis induced by BDL.

2.
J Hazard Mater ; 411: 125095, 2021 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-33858087

RESUMO

Biofilm formation has been frequently identified as a pathway of nosocomial infection in polymeric tubes used for patients of all ages. Biofilm formation on tube surfaces can lead to hygienic failure and cause diarrhea, stomach pain, inflammation, and digestive system disease. This study investigated the influence of polymeric tube materials in contact with water on the biomass formation potential and migration potential of microbially available carbon from plasticizers using a BioMig test. The thermoplastic elastomer tube, which is reusable, leached a relatively low amount of assimilable organic carbon to water. In contrast, the assimilable organic carbon migration potential of polyurethane was the most significant, 6-fold greater than that of the thermoplastic elastomer. Moreover, the same materials (e.g., silicone) produced via different manufacturing processes showed significant differences in migration behaviors. The potential biomass formation observed in polyurethane was approximately 7 × 109 cells cm-2 for both Aeromonas hydrophila and Escherichia coli strains. This study highlights the importance of choosing the correct material characteristics of polymeric tubes in contact with water to protect them from bacterial contamination. Therefore, manufacturers can use the BioMig test to evaluate and produce more hygienic and biostable tubes.

3.
Medicina (Kaunas) ; 57(3)2021 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-33800300

RESUMO

Background and Objectives: Tracheal or bronchial tears are potential complications of rigid bronchoscopy. This study aimed to investigate the acute complications and outcomes of using an insulation-tipped (IT) knife in combination with rigid bronchoscopic dilatation for treating benign tracheobronchial stenosis. Materials and Methods: We conducted a chart review of patients with benign tracheobronchial stenosis who were treated with rigid bronchoscopy and an IT knife at two referral centers. Treatment success was defined as a clinically stable state without worsening symptoms after 3 months of treatment. Results: Of the 23 patients with benign tracheobronchial stenosis, 15 had tracheal stenosis and 6 had main bronchial stenosis. Among them, three cases were of simple stenosis (13%), while the others were of complex stenosis (87%). The overall treatment success rate was 87.0%. Pneumomediastinum and subcutaneous emphysema occurred due to bronchial laceration in two cases of distal left main bronchial stenosis (8.7%), and no other significant acute complications developed. Silicone stents were inserted in 20 patients, and successful stent removal was possible in 11 patients (55.0%). Six of the seven stents inserted in patients with post-intubation tracheal stenosis were removed successfully (85.7%). However, most of the patients with post-tracheostomy tracheal stenosis required persistent stenting (80%). Pulmonary function was significantly increased after treatment, and the mean increase in the forced expiratory volume in 1 s was 391 ± 171 mL (160-700 mL). Conclusion: The use of an IT knife can be suggested as an effective and safe modality for rigid bronchoscopic treatment of benign tracheobronchial stenosis.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33894918

RESUMO

BACKGROUND: Laparoscopic surgery has been widely used for rectal cancer; however, its long-term outcomes remain controversial. This study aimed to assess the long-term oncological safety of laparoscopic surgery for rectal cancer using 10-year follow-up data of the Comparison of Open versus laparoscopic surgery for mid or low REctal cancer After Neoadjuvant chemoradiotherapy (COREAN) trial. METHODS: The COREAN trial is a, open-label, non-inferiority, randomised controlled trial. Eligible participants were aged 18-80 years, had cT3N0-2M0 middle or low rectal cancer with lesions located within 9 cm of the anal verge, and had been treated with preoperative chemoradiotherapy. Patients were randomly assigned (1:1) to open or laparoscopic surgery with a computer-generated random allocation sequence with a random permuted block design. Neither patients nor clinicians were masked to treatment assignment. Open or laparoscopic total mesorectal excision was done 6-8 weeks after the administration of preoperative concurrent chemoradiotherapy (fluoropyrimidines alone, doublet therapy, or triplet therapy) at a dose of 50·5 Gy over 5·5 weeks. Postoperative adjuvant chemotherapy was administered for 4 months. The primary endpoint of 3-year disease-free survival was published previously. Here, we report 10-year overall survival, disease-free survival, and local recurrence. Analyses were done in the modified intention-to-treat population of all participants who were randomly assigned and provided follow-up data. This study is registered with ClinicalTrials.gov, NCT00470951. FINDINGS: Of the 340 patients enrolled in the COREAN trial between April 4, 2006, and Aug 26, 2009 (170 patients in each group), two patients in the laparoscopic surgery group moved abroad and were lost to follow-up, so were not included in this 10-year analysis. The median duration of follow-up was 143 months (IQR 122-156). No differences were observed in 10-year overall survival (74·1% [95% CI 66·8-80·0] in the open surgery group vs 76·8% [69·6-82·5] in the laparoscopic surgery group; p=0·44), 10-year disease-free survival (59·3% [51·1-66·5] vs 64·3% [56·0-71·5]; p=0·20), or 10-year local recurrence (8·9% [5·2-15·0] vs 3·4% [1·4-7·9]; p=0·050) between the open surgery and laparoscopic surgery groups at 10 years after surgery. The stratified hazard ratios, adjusted for ypT and ypN classification and tumour regression grade, for open surgery versus laparoscopic surgery were 0·94 (95% CI 0·63-1·43) for overall survival, 1·05 (0·74-1·49) for disease-free survival, and 2·22 (0·78-6·34) for local recurrence. INTERPRETATION: The 10-year follow-up of the COREAN trial confirms the long-term oncological safety of laparoscopic surgery in patients with rectal cancer treated with preoperative chemoradiotherapy. Similar to open surgery, laparoscopic surgery does not compromise long-term survival outcomes in rectal cancer when performed by well trained surgeons. FUNDING: National Cancer Center, Goyang, South Korea.

5.
Polymers (Basel) ; 13(5)2021 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-33673576

RESUMO

Utilization of methods involving component integration has accelerated, owing to the growth of the smart mobile industry. However, this integration leads to interference issues between the components, thereby elucidating the importance of the electromagnetic interference (EMI) shielding technology to solve such issues. EMI shielding technology has been previously implemented via the reflection or absorption of electromagnetic waves by using conductive materials. Nevertheless, to tackle the recent changes in the industry, a transparent and flexible EMI shielding technology is necessitated. In this study, a transparent and flexible EMI shielding material was fabricated by filling a conductive binder in a film comprising an intaglio pattern; this was achieved by using the ultraviolet (UV) imprinting technology to realize mass production. Subsequently, changes in the aperture ratio and shielding characteristics were analyzed according to the structure of the pattern. Based on this analysis, a square pattern was designed and a film with an intaglio pattern was developed through a UV imprinting process. Furthermore, it was confirmed that the transmittance, conductivity, and EMI shielding rate of the film were altered while changing the coating thickness of the conductive particles in the intaglio pattern. The final film prepared in this study exhibited characteristics that satisfied the required EMI shielding performance for electric and electronic applications, while achieving flexible structural stability and transparency.

6.
PLoS One ; 16(3): e0249204, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33784360

RESUMO

Income inequality is known to have negative impacts on an economic system, thus has been debated for a hundred years past or more. Numerous ideas have been proposed to quantify income inequality, and the Gini coefficient is a prevalent index. However, the concept of perfect equality in the Gini coefficient is rather idealistic and cannot provide realistic guidance on whether government interventions are needed to adjust income inequality. In this paper, we first propose the concept of a more realistic and 'feasible' income equality that maximizes total social welfare. Then we show that an optimal income distribution representing the feasible equality could be modeled using the sigmoid welfare function and the Boltzmann income distribution. Finally, we carry out an empirical analysis of four countries and demonstrate how optimal income distributions could be evaluated. Our results show that the feasible income equality could be used as a practical guideline for government policies and interventions.

7.
Nitric Oxide ; 109-110: 42-49, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-33713800

RESUMO

The roles of nitrate and nitrite ions as nitric oxide (NO) sources in mammals, complementing NOS enzymes, have recently been the focus of much research. We previously reported that rat skeletal muscle serves as a nitrate reservoir, with the amount of stored nitrate being highly dependent on dietary nitrate availability, as well as its synthesis by NOS1 enzymes and its subsequent utilization. We showed that at conditions of increased NO need, this nitrate reservoir is used in situ to generate nitrite and NO, at least in part via the nitrate reductase activity of xanthine oxidoreductase (XOR). We now further investigate the dynamics of nitrate/nitrite fluxes in rat skeletal muscle after first increasing nitrate levels in drinking water and then returning to the original intake level. Nitrate/nitrite levels were analyzed in liver, blood and several skeletal muscle samples, and expression of proteins involved in nitrate metabolism and transport were also measured. Increased nitrate supply elevated nitrate and nitrite levels in all measured tissues. Surprisingly, after high nitrate diet termination, levels of both ions in liver and all muscle samples first declined to lower levels than the original baseline. During the course of the overall experiment there was a gradual increase of XOR expression in muscle tissue, which likely led to enhanced nitrate to nitrite reduction. We also noted differences in basal levels of nitrate in the different types of muscles. These findings suggest complex control of muscle nitrate levels, perhaps with multiple processes to preserve its intracellular levels.

8.
Artigo em Inglês | MEDLINE | ID: mdl-33538357

RESUMO

BACKGROUND AND AIM: Acute variceal bleeding (AVB) is a fatal adverse event of cirrhosis, and endoscopic band ligation (EBL) is the standard treatment for AVB. We developed a novel bedside risk-scoring model to predict the 6-week mortality in cirrhotic patients undergoing EBL for AVB. METHODS: Cox regression analysis was used to assess the relationship of clinical, biological, and endoscopic variables with the 6-week mortality risk after EBL in a derivation cohort (n = 1373). The primary outcome was the predictive accuracy of the new model for the 6-week mortality in the validation cohort. Moreover, we tested the adequacy of the mortality risk-based stratification and the discriminative performance of our new model in comparison with the Child-Turcotte-Pugh (CTP) and the model for end-stage liver disease scores in the validation cohort (n = 200). RESULTS: On multivariate Cox regression analysis, five objective variables (use of beta-blockers, hepatocellular carcinoma, CTP class C, hypovolemic shock at initial presentation, and history of hepatic encephalopathy) were scored to generate a 12-point risk-prediction model. The model stratified the 6-week mortality risk in patients as low (3.5%), intermediate (21.1%), and high (53.4%) (P < 0.001). Time-dependent area under the receiver operating characteristic curve for 6-week mortality showed that this model was a better prognostic indicator than the CTP class alone in the derivation (P < 0.001) and validation (P < 0.001) cohorts. CONCLUSIONS: A simplified scoring model with high potential for generalization refines the prediction of 6-week mortality in high-risk cirrhotic patients, thereby aiding the targeting and individualization of treatment strategies for decreasing the mortality rate.

9.
PLoS One ; 16(2): e0247252, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33626070

RESUMO

BACKGROUND: We sought to investigate intentions to undergo primary screening with colonoscopy in an attempt to predict future colorectal cancer screening behaviors and the feasibility of implementing colonoscopy as the primary screening modality for colorectal cancer in the National Cancer Screening Program (NCSP) of Korea. METHODS: Data were obtained from a nationwide online survey conducted in 2018. The survey included a total of 800 eligible adults aged over 45 years. Study measures included the history of screening colonoscopy within the past 10 years and intentions to undergo primary screening with colonoscopy under the NCSP based on the five constructs of the Health Belief Model. Logistic regression analysis was conducted to examine factors associated with intentions to undergo primary screening with colonoscopy. RESULTS: Approximately 77% of the participants expressed strong willingness to undergo primary screening with colonoscopy under the NCSP. Higher perceived severity and perceived benefits were significantly associated with stronger intentions to undergo screening with colonoscopy (adjusted odds ratio [aOR], 1.53; 95% confidence interval [CI], 1.10-2.14 and aOR, 2.74; 95% CI, 1.76-4.28, respectively). Greater perceived barriers (aOR, 0.65; 95% CI, 0.45-0.93) were significantly associated with weaker intentions. Cues to action elicited the strongest screening intentions (aOR, 8.28; 95% CI, 5.23-13.12). CONCLUSION: The current study findings highlight the need for increasing awareness of the severity of CRC and the benefits of colonoscopy screening. Family-orientated recommendation strategies and reducing complications may boost an individual's intentions to undergo colonoscopy.

10.
BMJ Case Rep ; 14(2)2021 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-33542008

RESUMO

A 76-year-old man was referred to our clinic after a foreign body seen in his sigmoid colon during a colonoscopy. He had undergone three operations for a left inguinal hernia within the previous 8 years, and the first procedure was a laparoscopic totally extraperitoneal approach. Four years later, removal of migrated and infected mesh was conducted by open approach. He then had a positive stool occult blood test for routine check-up 4 years after the remnant mesh removal. An ill-defined lesion was identified on colonoscopy. CT revealed a 2.7 cm diameter enhancing lesion in the sigmoid colon. Laparoscopic sigmoidectomy was performed, and remnant mesh fragment was found in the sigmoid colon and removed. The migrated mesh could not be wholly removed by open abdominal approach and the remnant mesh fragment migrated to sigmoid colon. It suggests the importance of a laparoscopic approach to remove the entire mesh.


Assuntos
Colo Sigmoide/cirurgia , Procedimentos Cirúrgicos do Sistema Digestório , Hérnia Inguinal/complicações , Herniorrafia , Laparoscopia , Telas Cirúrgicas/efeitos adversos , Idoso , Humanos , Masculino , Sangue Oculto , Complicações Pós-Operatórias/cirurgia
11.
Sci Rep ; 11(1): 3538, 2021 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-33574345

RESUMO

To identify low anterior resection syndrome (LARS) patterns and their associations with risk factors and quality of life (QOL). This cross-sectional study analyzed patients who underwent restorative anterior resection for left-sided colorectal cancer at Seoul National University Hospital, Seoul, Republic of Korea. We administered LARS questionnaires to assess bowel dysfunction and quality of life between April 2017 and November 2019. LARS patterns were classified based on factor analyses. Variable effects on LARS patterns were estimated using logistic regression analysis. The risk factors and quality of life associated with dominant LARS patterns were analyzed. Data of 283 patients with a median follow-up duration of 24 months were analyzed. Major LARS was observed in 123 (43.3%) patients. Radiotherapy (odds ratio [OR]: 2.851, 95% confidence interval [95% CI]: 2.504-43.958, p = 0.002), low anastomosis (OR: 10.492, 95% CI: 2.504-43.958, p = 0.001), and complications (OR: 2.163, 95% CI: 1.100-4.255, p = 0.025) were independently associated with major LARS. LARS was classified into incontinence- or frequency-dominant types. Risk factors for incontinence-dominant LARS were radiotherapy and complications, whereas those for frequency-dominant LARS included low tumor location. Patients with incontinence-dominant patterns showed lower emotional function, whereas those with frequency-dominant patterns showed lower global health QOL, lower emotional, cognitive, and social functions, and higher incidence of pain and diarrhea. Frequency-dominant LARS had a greater negative effect on QOL than incontinence-dominant LARS. These patterns could be used for preoperative prediction and postoperative treatment of LARS.

12.
Anal Chim Acta ; 1151: 338252, 2021 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-33608074

RESUMO

Herein, we report a colorimetric sensing system for the detection of highly virulent bacteria, Escherichiacoli O157:H7, in sausage by utilizing magnetic separation and enzyme-mediated signal amplification on paper disc. For magnetic separation, Poly-l-lysine coated starch magnetic particles (PLL@SMPs) were synthesized and utilized for the separation and concentration of the bacteria in sample suspension. Horseradish peroxidase-conjugated antibody (HRP-Antibody) and 3,3',5,5'- tetramethylbenzidine (TMB) were employed for the specific signal amplification in the presence of target bacteria. The synthesized PLL@SMPs showed an excellent capture efficiency (>90%) for the pathogenic bacteria in large volume sample suspension. The intrinsic problems associated with the non-specific binding of sensing components that lead to the high background signal and low sensitivity in colorimetric detection was successfully resolved by employing hyaluronic acid as a blocking agent. The effective separation and concentration of target bacteria by PLL@SMPs and target-specific signal amplification with exceptionally high signal to noise ratio enabled the detection of target bacteria with a detection limit in the single digit regime. The sensing system proposed in this study was successfully used for the detection of the target pathogenic bacteria, E. coli O157:H7, in sausage sample with the limit of detection (LOD) as low as 30.8 CFU/mL with 95% probability. The simple nature of paper-based detection system with a great sensitivity and specificity would provide an effective means of evaluating the safety of food and environmental samples.

13.
Anticancer Res ; 41(2): 687-697, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33517273

RESUMO

BACKGROUND/AIM: We investigated drugs that could sensitize P-glycoprotein (P-gp)-overexpressing drug-resistant cancer cells to vincristine (VIC) or eribulin treatment and assessed their associated mechanisms of action. MATERIALS AND METHODS: We investigated 15 bipolar drugs (quetiapine, risperidone, clozapine, asenapine, iloperidone, paliperidone, ziprasidone, trifluoperazine, loxapine succinate, pilocarpine, valproic acid, carbamazepine, levetiracetam, topiramate, and felbamate) to identify drugs with a sensitizing effect on VIC-resistant KBV20C cells at relatively low doses. Fluorescence-activated cell sorting (FACS), annexin V analyses, and rhodamine uptake tests were performed to further investigate the mechanism of action. RESULTS: We found that co-treatment with half the tested drugs (quetiapine, iloperidone, trifluoperazine, loxapine, risperidone, ziprasidone, or felbamate) at low doses could highly sensitize VIC-resistant KBV20C cells. With lower amounts of the bipolar drugs or VIC, we found that among the 15 bipolar drugs tested, 2 combinations (VIC-quetiapine and VIC-trifluoperazine) had much higher sensitization effects, suggesting that lower effective doses were sufficient for sensitizing P-gp-overexpressing resistant cells compared to those required with the other drugs. Furthermore, when we compared quetiapine and trifluoperazine to previously known bipolar drugs (fluphenazine, thioridazine, pimozide, or aripiprazole), we found that aripiprazole, administered at lower doses, had a much higher sensitization effect. We also demonstrated that co-treatment with another anti-mitotic drug (eribulin) increased the sensitization of KBV20C cells similar to VIC. We also found that aripiprazole had higher P-gp-inhibitory activity than the other bipolar drugs, indicating that this activity was involved in the higher level of VIC-aripiprazole sensitization. CONCLUSION: Co-treatment of anti-mitotic drug-resistant cancer cells with a low dose of aripiprazole had the strongest sensitization effect and is highly dependent on P-gp-inhibitory activity.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/antagonistas & inibidores , Antineoplásicos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Antipsicóticos/farmacologia , Aripiprazol/farmacologia , Reposicionamento de Medicamentos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Furanos/farmacologia , Cetonas/farmacologia , Neoplasias Bucais/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Vincristina/farmacologia , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Humanos , Neoplasias Bucais/genética , Neoplasias Bucais/metabolismo , Neoplasias Bucais/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia
14.
Surg Endosc ; 2021 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-33492504

RESUMO

BACKGROUND: Self-expanding metallic stents (SEMSs) are used as a bridge to surgery in patients with obstructive colorectal cancer. However, the role of laparoscopic resection after successful stent deployment is not well established. We aimed to compare the oncologic outcomes of laparoscopic vs open surgery after successful colonic stent deployment in patients with obstructive left-sided colorectal cancer. METHODS: In this multicenter study, 179 (97 laparoscopy, 82 open surgery) patients with obstructive left-sided colorectal cancer who underwent radical resection with curative intent after successful stent deployment were retrospectively reviewed. To minimize bias, we used inverse probability treatment-weighted propensity score analysis. The short- and long-term outcomes between the groups were compared. RESULTS: Both groups had similar demographic and tumor characteristics. The operation time was longer, but the degree of blood loss was lower in the laparoscopy than in the open surgery group. There were nine (9.3%) open conversions. After adjustment, the groups showed similar patient and tumor characteristics. The 5-year disease-free survival (DFS) (laparoscopic vs open: 68.7% vs 48.5%, p = 0.230) and overall survival (OS) (laparoscopic vs open: 79.1% vs 69.0%, p = 0.200) estimates did not differ significantly across a median follow-up duration of 50.5 months. Advanced stage disease (DFS: hazard ratio [HR] 1.825, 95% confidence interval [CI]: 1.072-3.107; OS: HR 2.441, 95% CI 1.216-4.903) and post-operative chemotherapy omission (DFS: HR 2.529, 95% CI 1.481-4.319; OS: HR 2.666, 95% CI 1.370-5.191) were associated with relatively worse long-term outcomes. CONCLUSION: Stent insertion followed by laparoscopy with curative intent is safe and feasible; the addition of post-operative chemotherapy should be considered after successful treatment.

15.
FASEB J ; 35(1): e21221, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33337564

RESUMO

Alterations in complement component 3 (C3) expression has been reported to be linked to several bowel diseases including Crohn's disease, inflammatory bowel disease, and ulcerative colitis; however, the association with constipation has never been investigated. In this study, we aimed to investigate the correlation between C3 regulation and constipation development using a C3 deficiency model. To achieve these, alterations in stool excretion, transverse colon histological structure, and mucin secretion were analyzed in FVB/N-C3em1Hlee /Korl (C3 knockout, C3 KO) mice with the deletion of 11 nucleotides in exon 2 of the C3 gene. The stool excretion parameters, gastrointestinal transit, and intestine length were remarkably decreased in C3 KO mice compared with wild-type (WT) mice, although there was no specific change in feeding behavior. Furthermore, C3 KO mice showed a decrease in mucosal and muscle layer thickness, alterations in crypt structure, irregular distribution of goblet cells, and an increase of mucin droplets in the transverse colon. Mucin secretion was suppressed, and they accumulated in the crypts of C3 KO mice. In addition, the constipation phenotypes detected during C3 deficiency were confirmed in FVB/N mice treated with C3 convertase inhibitor (rosmarinic acid (RA)). Similar phenotypes were observed with respect to stool excretion parameters, gastrointestinal transit, intestine length, alterations in crypt structure, and mucin secretion in RA-treated FVB/N mice. Therefore, the results of the present study provide the first scientific evidence that C3 deficiency may play an important role in the development of constipation phenotypes in C3 KO mice.

16.
Transl Oncol ; 14(2): 101000, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33352502

RESUMO

A metastasis of colorectal cancer is difficult to diagnose, and has a poor prognosis. Therefore, we tried to elucidate the possibility of a diagnostic and prognostic marker. Exosomal miR-193a and let-7g were sorted by miRNA microarray. The expression of miR-193a in the PTM group was lower than that of the primary CRC group, and the expression of let-7g was higher than that of the primary CRC. MMP16 and CDKN1A expression was confirmed respectively for target genes of two miRNAs. When the mimics of these miRNAs were treated with cell lines, both MMP16 and CDKN1A decreased intracellular expression. Cell invasiveness and proliferation were decreased by miR-193a and increased by let-7g. The differences in expression of exosomal miR-193a and let-7g extracted from the plasma of patients were classified as cancer progression indicators. Furthermore, the survival rate decreased in the group with low miR-193a expression and high let-7g expression. Our study confirmed the possibility of using this as a diagnostic and prognostic marker for colorectal cancer by measuring the expression levels of exosomal miR-193a and let-7g in blood.

17.
Biomed Pharmacother ; 132: 110950, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33254440

RESUMO

There is an increasing interest in natural products and their derivatives with therapeutic benefits and less side effects compared to steroid therapy. Benzofuran derivatives display biological effects including anti-inflammatory effects. The present study aims to investigate whether (3-(7-methoxy-2-p-tolyl benzofuran-5-yl) propan-1-ol) (DK-1108), new synthetic benzofuran compound exerts anti-asthmatic effects in vitro and in vivo. DK-1108 strongly reduced the production of inflammatory mediators, cytokines and chemokines in RAW264.7 and A549 cells. DK-1108 significantly regulated the levels of AKT/MAPKs/c-Jun activation, AP-1 luciferase activity and ICAM-1 expression. Furthermore, DK-1108 effectively suppressed the adhesion of A549 and EOL-1 cells. In OVA-induced asthmatic mice, DK-1108 decreased the levels of IL-5/IL-13/IgE production, eosinophils/macrophages influx, ICAM-1/MCP-1 expression, mucus secretion and airway hyperresponsiveness (AHR). These effects of DK-1108 were accompanied by downregulation of MAPKs activation. Therefore, we suggest that DK-1108 exerts protective effect against airway inflammation and mucus overproduction, and therefore could be valuable therapeutic agent for treatment in asthma.

18.
Cancer Med ; 2020 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-33230884

RESUMO

BACKGROUND: Smoking is a well-known risk factor for colorectal cancer incidence; however, the effect of smoking before and after cancer diagnosis on mortality has not been addressed well. Thus, we aimed to evaluate the association of prediagnosis and postdiagnosis smoking status and mortality among colorectal cancer patients. METHODS: A retrospective cohort consisted of 37,079 male colorectal cancer patients. Smoking status was defined from information within 2 years of colorectal cancer diagnosis for prediagnosis and at least 1 year later for postdiagnosis. The prediagnostic and postdiagnostic smoking status were categorized into four groups (nonsmoker/nonsmoker, nonsmoker/smoker, smoker/nonsmoker, and smoker/smoker). Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using the Cox proportional hazard model. RESULTS: During a median of 6.3 years of follow-up, a total of 3980 deaths and 2137 deaths from colorectal cancer occurred. The number of prediagnosis smokers were 11,100 and 62.4% of them quitted smoking after the diagnosis. Significantly elevated mortality rate in prediagnosis smokers was observed regardless of postdiagnosis smoking status (smoker/nonsmoker [HR, 1.30; 95% CI, 1.20-1.41] and smoker/smoker [HR, 1.21; 95% CI, 1.09-1.34]). Among patients treated with surgical operation only, those who quit smoking after diagnosis showed lower mortality rates compared to continual smokers (HR, 0.80; 95% CI, 0.67-0.96). CONCLUSIONS: Smoking before cancer diagnosis rather than postdiagnosis has stronger impact on prognosis colorectal cancer patients, and quitting smoking may improve survival, especially among early stage colorectal cancer patients.

19.
J Hazard Mater ; : 124530, 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33243649

RESUMO

This study investigated the effect of powdered activated carbon and calcium on trihalomethane toxicity in zebrafish embryos and larvae in hybrid membrane bioreactors. Two hybrid membrane bioreactors were configured with the addition of powdered activated carbon or calcium to reduce the trihalomethane formation potential. Trihalomethane formation decreased by approximately 37.2% and 30.3% in membrane bioreactor-powdered activated carbon and membrane bioreactor-calcium, respectively. Additionally, the toxic effect of trihalomethane formation was examined on zebrafish embryos and larvae. About 35% of the embryos exposed to trihalomethanes (800 ppb) showed signs of deformation, with the majority displaying coagulation within 24 h after exposure. Color preference tests, which were conducted to identify any abnormal activities of the embryos, showed an increase in preference from short to longer wavelengths upon exposure to high levels of trihalomethanes. This may indicate damage to the optical organs in zebrafish when exposed to trihalomethanes. Behavioral analysis showed reduced mobility of zebrafish larvae under different trihalomethane concentrations, indicating a decrease in the average activity time with an increasing trihalomethane concentration. The membrane bioreactor effluents were toxic to zebrafish embryos and larvae in the presence of high trihalomethane concentrations. To understand the mechanism behind trihalomethane toxicity, further studies are needed.

20.
Int Immunopharmacol ; 88: 107002, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33182035

RESUMO

3,4,5-Trihydroxycinnamic acid (THCA) has been reported to possess anti-inflammatory activity. However, the effect of THCA for treating allergic asthma was unknown. Therefore, in the present study, the anti-asthmatic effects of THCA were studied in both in vitro and in vivo studies. In phorbol 12-myristate 13-acetate (PMA)-stimulated A549 airway epithelial cells, THCA pretreatment decreased the mRNA expression and secretion of interleukin (IL)-8, monocyte chemoattractant protein-1 (MCP-1), and intercellular adhesion molecules 1 (ICAM-1), and reduced the mRNA expression of matrix metalloproteinase 9 (MMP-9). THCA also inhibited PMA-induced protein kinase B (AKT), mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) activation in A549 cells. In lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages, THCA pretreatment suppressed the mRNA expression of ICAM-1 and MMP-9. In addition, THCA suppressed the adhesion of EOL and A549 cells. In ovalbumin (OVA)-administered asthmatic mice, THCA exerted inhibitory activity on IL-5, IL-13, and MCP-1 in bronchoalveolar lavage fluid (BALF) and on OVA-specific immunoglobulin E (IgE) in serum. THCA attenuated the numbers of inflammatory cells in BALF and the influx of inflammatory cell in lung tissues. Furthermore, THCA downregulated the levels of inducible nitric oxide (iNOS), cyclooxygenase-2 (COX-2), and leukotriene B4 (LTB4) expression, mucus production and CREB phosphorylation as well as Penh value. These effects were accompanied by suppression of AKT, extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and NF-κB activation. Therefore, the results of the current study suggest that THCA may be a valuable adjuvant or therapeutic in the prevention or treatment of allergic asthma.

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