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1.
Radiother Oncol ; 165: 166-173, 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34748856

RESUMO

BACKGROUND AND PURPOSE: To validate a computed tomography (CT)-based deep learning prognostication model, originally developed for a surgical cohort, in patients with primary lung cancer undergoing stereotactic ablative radiotherapy (SABR). MATERIALS AND METHODS: This retrospective study identified patients with clinical stage T1-2N0M0 lung cancer treated with SABR between 2013 and 2018. The outcomes were local recurrence-free survival (LRFS), disease-free survival (DFS), and overall survival (OS). The discrimination performance of the model, which extracted a quantitative score of cumulative risk for an adverse event up to 900 days, was evaluated using time-dependent receiver operating characteristic curve analysis. Multivariable Cox regression was performed to investigate the independent prognostic value of the model output adjusting for clinical factors including age, sex, smoking status, and clinical T category. RESULTS: In total, 135 patients (median age, 78 years; 101 men; 78 [57.8%] adenocarcinomas and 57 [42.2%] squamous cell carcinomas) were evaluated. Most patients (117/135) were treated with 48-60 Gy in four fractions. Median biologically effective dose was 150.0 Gy (interquartile range, 126.9, 150.0 Gy). For LRFS, the area under the curve (AUC) was 0.72 (95% confidence interval [CI]: 0.58, 0.87). The AUCs were 0.70 (95% CI: 0.60, 0.81) for DFS and 0.66 (95% CI: 0.54, 0.77) for OS. Model output was associated with LRFS (adjusted hazard ratio [HR], 1.043; 95% CI: 1.003, 1.085; P = 0.04), DFS (adjusted HR, 1.03; 95% CI: 1.01, 1.05; P = 0.008), and OS (adjusted HR, 1.025; 95% CI: 1.002, 1.047; P = 0.03). CONCLUSION: This study showed external validity and transportability of the CT-based deep learning prognostication model for radiotherapy candidates.

2.
Artigo em Inglês | MEDLINE | ID: mdl-34801434

RESUMO

BACKGROUND: Wounds remain the most important cause of postoperative mortality and morbidity and generate considerable additional social and healthcare costs. Most wounds are caused by various coliforms, Enterococcus fecalis, Proteus sp., and multidrug resistant Staphylococcus aureus. Wound is one of the leading cause of infections in the under developed and developing countries than developed nations. METHODS: A total of 43 samples associated with bacteremia and wound infection were collected. Biochemical characterization and culture characteristics of the drug resistant isolates were studied using MacConkey agar, blood agar and mannitol-salt agar. Antibiotic susceptibility analysis of the isolated strains was performed by disc diffusion method using various antibiotics. Prevalence of dug resistance among bacteria isolated from the wound was studied. The ability of Beta lactamase antibiotic producing bacterial strains were analyzed. RESULTS: A total of 168 bacterial strains were isolated showed high resistant towards ampicillin (89%), ciprofloxacin (90.8), cefepine (90.5), piperacillin (91.8), oxacillin (92.5), and imipenem (96.5). The isolated bacterial strains showed monobacterial as well as polybacterial growth on the surface of the wound. The isolated bacterial strains revealed 89% sensitivity against norfloxacin and 94.9 sensitivity against vancomycin. About 26% of bacterial strains degraded quinolones, whereas only 14% clinical isolates showed their ability to degrade aminoglycosides. A total of 27% bacteria degraded tetracycline and 51% of isolates degraded carbapenems compounds. Interestingly, E. faecalis was resistant against antibiotics such as, Oxacillin, Nalidic acid, Ofloxacin, Erythromycin, Norfloxacin, Ciprofloxacin, Ampicillin, Tetracycline, Cefepine, Amikacin, Cefurooxime, Vancomycin, Piperacillin, Imipenem and Gentamycin. Moreover, Proteus species was resistant against certain numbers of antibiotics namely, Ampicillin, Piperacillin, Oxacillin, Nalidic acid, Tetracycline, Erythromycin, Cefurooxime, Nitrofurantoin, Vancomycin and Imipenem. CONCLUSIONS: The isolated bacterial strains were resistant against various drugs including vancomycin. Staphylococci, and E. faecalisis strains showed resistance against various classes of antibiotics.

3.
Radiat Oncol ; 16(1): 222, 2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34794471

RESUMO

BACKGROUND: The purpose of this study was to compare the treatment efficacy and safety of re-irradiation (re-RT) using stereotactic ablative radiotherapy (SABR) and initial SABR for primary, recurrent lung cancer or metastatic lung tumor. METHODS: A retrospective review of the medical records of 336 patients who underwent lung SABR was performed. Re-RT was defined as the overlap of the 70% isodose line of second-course SABR with that of the initial radiotherapy, and 20 patients were classified as the re-RT group. The median dose of re-RT using SABR was 54 Gy (range 48-60 Gy), and the median fraction number was 4 (range 4-6). One-to-three case-matched analysis with propensity score matching was used, and 60 patients were included in the initial SABR group of the matched cohort. RESULTS: The 1- and 2-year local control rates for the re-RT group were 73.9% and 63.3% and those for the initial SABR group in the matched cohort were 92.9% and 87.7%, respectively (P = 0.013). There was no difference in distant metastasis-free, progression-free, and overall survival rates. The crude grade ≥ 2 toxicity rates were 40.0% for the re-RT group and 25.0% for the initial SABR group (P = 0.318). Re-RT group had higher acute grade ≥ 2 toxicity rates (25.0% vs 5.0%, P = 0.031). One incident of grade 3 toxicity (pulmonary) was reported in the re-RT group; there was no grade 4‒5 toxicity. CONCLUSIONS: The local control rate of the in-field re-RT SABR was lower than that of the initial SABR without compromising the survival rates. The toxicity of re-RT using SABR was acceptable.

4.
Clin Psychopharmacol Neurosci ; 19(4): 618-627, 2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34690117

RESUMO

Objective: The cyclic nucleotide-gated channel (Cng) regulates synaptic efficacy in brain neurons by modulating Ca2+ levels in response to changes in cyclic nucleotide concentrations. This study investigated whether the expression of Cng channel, cyclic nucleotide-gated channel subunit beta 1 (Cngb1) exhibited any relationship with the pathophysiology of schizophrenia in an animal model and whether genetic polymorphisms of the human gene were associated with the progression of schizophrenia in a Korean population. Methods: We investigated whether Cngb1 expression was related to psychiatric disorders in a mouse model of schizophrenia induced by maternal immune activation. A case-control study was conducted of 275 schizophrenia patients and 410 controls with single-nucleotide polymorphisms (SNPs) in the 5'-near region of CNGB1. Results: Cngb1 expression was decreased in the prefrontal cortex in the mouse model. Furthermore, the genotype frequency of a SNP (rs3756314) of CNGB1 was associated with the risk of schizophrenia. Conclusion: Our results suggest that CNGB1 might be associated with schizophrenia susceptibility and maternal immune activation. Consequently, it is hypothesized that CNGB1 may be involved in the pathophysiology of schizophrenia.

5.
Front Oncol ; 11: 741071, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34631578

RESUMO

The purpose of this study was to investigate the impact of sarcopenia and body composition change during primary treatment on survival outcomes in patients with early cervical cancer. We retrospectively identified patients diagnosed with 2009 International Federation of Gynecology and Obstetrics stage IB1-IIA2 cervical cancer who underwent primary radical hysterectomy between 2007 and 2019. From pre-treatment CT scans (n = 306), the skeletal muscle area at the third lumbar vertebra (L3) and the waist skeletal muscle volume were measured using an artificial intelligence-based tool. These values were converted to the L3 and volumetric skeletal muscle indices by normalization. We defined L3 and volumetric sarcopenia using 39.0 cm2/m2 and the first quartile (Q1) value, respectively. From pre- and post-treatment CT scan images (n = 192), changes (%) in waist skeletal muscle and fat volumes were assessed. With the use of Cox regression models, factors associated with progression-free survival (PFS) and overall survival (OS) were analyzed. Between the L3 sarcopenia and non-sarcopenia groups, no differences in PFS and OS were observed. In contrast, volumetric sarcopenia was identified as a poor prognostic factor for PFS (adjusted hazard ratio [aHR], 1.874; 95% confidence interval [CI], 1.028-3.416; p = 0.040) and OS (aHR, 3.001; 95% CI, 1.016-8.869; p = 0.047). During primary treatment, significant decreases in waist skeletal muscle (median, -3.9%; p < 0.001) and total fat (median, -5.3%; p < 0.001) were observed. Of the two components, multivariate analysis revealed that the waist fat gain was associated with worse PFS (aHR, 2.007; 95% CI, 1.009-3.993; p = 0.047). The coexistence of baseline volumetric sarcopenia and waist fat gain further deteriorated PFS (aHR, 2.853; 95% CI, 1.257-6.474; p = 0.012). In conclusion, baseline volumetric sarcopenia might be associated with poor survival outcomes in patients with early cervical cancer undergoing primary RH. Furthermore, sarcopenia patients who gained waist fat during primary treatment were at a high risk of disease recurrence.

6.
J Fungi (Basel) ; 7(8)2021 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-34436171

RESUMO

The present study was carried out to analyze the potential of fungi isolated from the rhizosphere of soybean, brinjal, tomato, and potato plants. The density of fungi varied in the pot soil and rhizosphere after Paecilomyces formosus MD12 treatment. The P. formosus MD12 population was 6.3 ± 0.13 × 104 CFU g-1 in the pot planted with brinjal, and the population increased in the rhizosphere (6.72 ± 0.41 × 104 CFU g-1). P. formosus MD12 was cultured in the production medium, and the supernatant was used for egg inhibition studies on a root-knot nematode parasite, Meloidogyne incognita. It was revealed that maximum egg inhibition (94.7 ± 6.2%) was obtained at 100% concentration of extract. The culture supernatant from P. formosus MD12 affected the development of M. incognita juvenile, and the mortality rate was maximum after 96 h (95 ± 6%). Mortality was reduced when treated with 25%, 50%, and 75% supernatant. At 1 × 107 mL-1 of spore suspension, we found reductions of 71.6 ± 3.3% nematode populations in the soil, 60.7 ± 2.2% from the root, and 63.6 ± 2.4% egg mass compared with the control in the pot experiment. The culture supernatant applied at the 10% level showed a maximum mean reduction of the nematode population in roots (72.4 ± 2.2%), soil (77.9 ± 2.5%), and egg masses (73.2 ± 1.5%), respectively. The presence of P. formosus MD12 in a soil environment could antagonize nematode parasites and improve soil amendment. The P. formosus MD12 strain showed good biocontrol ability against the root-knot nematode, M. incognita, under in vitro and green house experimental condition.

7.
Anim Cells Syst (Seoul) ; 25(4): 245-254, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34408813

RESUMO

The time-sequential change in immune-related gene expression of the glioblastoma cell line after irradiation was evaluated to speculate the effect of combined immunotherapy with radiotherapy. The U373 MG glioblastoma cell line was irradiated with 6 Gy single dose. Next-generation sequencing (NGS) transcriptome data was generated before irradiation (control), and at 6, 24, and 48 h post-irradiation. Immune-related pathways were analyzed at each time period. The same analyses were also performed for A549 lung cancer and U87 MG glioblastoma cell lines. Western blotting confirmed the programmed death-ligand 1 (PD-L1) expression levels over time. In the U373 MG cell line, neutrophil-mediated immunity, type I interferon signaling, antigen cross-presentation to T cell, and interferon-γ signals began to increase significantly at 24 h and were upregulated until 48 h after irradiation. The results were similar to those of the A549 and U87 MG cell lines. Without T cell infiltration, PD-L1 did not increase even with upregulated interferon-γ signaling in cancer cells. In conclusions, in the glioblastoma cell line, immune-related signals were significantly upregulated at 24 and 48 h after irradiation. Therefore, the time interval between daily radiotherapy might not be enough to expect full immune responses by combined immune checkpoint inhibitors and newly infiltrating immune cells after irradiation.

8.
J Am Coll Nutr ; : 1-7, 2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-34282996

RESUMO

AIM: The study was aimed to assess the ability of Borassus flabellifer haustorium methanolic extract (BHE) on de novo glutathione biosynthesis in normal and pro-oxidant exposed cells via Nuclear factor erythroid 2-related factor 2 (Nrf2) and haeme oxygenase-1 (HO1) signaling in 2,2'-Azobis(2-methylpropionamidine) di-hydrochloride (AAPH) induced cytotoxicity in normal intestinal epithelial cells (IEC-6 cells). METHODS: The in vitro antioxidant activity was determined in terms of radical scavenging and ex vivo hemolysis. The cytoprotective effect was studied using AAP H as the alkoxyl radical inducer in IEC-6 cell model. The mechanistic basis of protection is determined by Nrf2/HO1 expression using qPCR. RESULTS: In vitro screening observed DPPH, hydrogen peroxide and ABTS radical scavenging activity for the BHE; further, BHE also protected the oxidative hemolysis in the erythrocytes induced by AAPH. In IEC-6 cells, AAPH treatment significantly reduced the cell viability (p < 0.001) by inducing lipid peroxidation. Further, there observed a significant reduction in the activities of enzymes involved in the de novo glutathione biosynthesis (p < 0.01) and glutathione reductase in these cells. However, pretreatment with BHE (10, 25 and 50 µg/mL) dose-dependently protected from the cytotoxicity of AAPH-derived alkoxyl radicals (p < 0.05); besides, the de novo glutathione biosynthesis and regeneration of GSH from oxidized form was also increased in these cells. In corroboration with the biochemical parameters, the Nrf2/HO1 expression was upregulated by the BHE pretreatment concomitantly reducing the cellular lipid peroxidation products. The improvement glutathione biosynthesis was also observed in BHE alone treated cells. CONCLUSION: The study indicated the potential of methanolic extract of Borassus flabellifer haustorium in enhancing the de novo glutathione biosynthesis in normal and pro-oxidant exposed cells by Nrf2/HO1 dependent manner, concomitantly mitigating the toxicity of AAPH-derived alkoxyl radicals in intestinal epithelial cells.

9.
Environ Res ; 202: 111718, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34297936

RESUMO

The essential oil isolated from plants is widely utilized as eco-friendly biocides and antibacterial agents. Curcuma amada, commonly known as mango ginger, is well-known for its applications in the food and aromatics industry for its significant mango-like aroma. The present study compared the different C. amada essential oils prepared by hydrodistillation (CHD), steam distillation (CSD), microwave-assisted extraction (MAE) and ultrasound-assisted extraction (UAE), for their chemical composition, antibacterial, larvicidal and insecticidal properties. GC/MS analysis indicated the presence of compounds including α-pinene, ß-myrcene, p-cymene, (Z)-ß-ocimene, Camphor, linalyl acetate, safrole, ar-curcumene, and ß-curcumene in the different C. amada essential oils. The antibacterial activity was observed against different strains of microbes, with a higher efficacy in the essential oils prepared by UAE and MAE methods. Apart from these, the MAE, UAE, CSD, and CHD were also shown to have significantly higher larvicidal activity against Aedes, Culex, and Armigeres species; however, no toxic effect was observed in non-targeted species like fishes and Allium cepa model of genotoxicity. Further, these essential oils were also found to have significant contact and fumigant toxicity as well as repellency against pests of stored grains (Sitophilus and Tribolium). Considering these results, the present study assumes that Curcuma amada essential oils may be a source of ecofriendly insecticides and antibacterial agents.


Assuntos
Desinfetantes , Gengibre , Inseticidas , Mangifera , Óleos Voláteis , Antibacterianos/farmacologia , Curcuma , Óleos Voláteis/farmacologia , Rizoma
10.
Sci Rep ; 11(1): 12369, 2021 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-34117284

RESUMO

We tested the feasibility of pulmonary vein (PV) and left atrial (LA) posterior wall isolation using non-invasive stereotactic ablative body radiotherapy (SABR) and investigated pathological changes in irradiated lesions in a canine model. Seven male Mongrel dogs received single-fraction 33 Gy SABR. We designed the en-bloc circular target of total PVs and LA posterior wall to avoid the esophagus. The circular box lesion included the LA roof and ridge, low posterior wall, and posterior interatrial septum. At 6 weeks or 4 months post-SABR, electrical isolation of the SABR lesion was confirmed using LA posterior wall pacing, and histopathological review was performed. Electrical isolation of all PVs and the LA posterior wall was achieved in three of five dogs in the 4-month group. There was one target failure and one sudden death at 15 weeks. Although two dogs in the 6-week group failed to achieve electrical lesion isolation, the irradiated atrial myocardium showed diffuse hemorrhage with inflammatory cell infiltration. In successfully isolated 4-month model dogs, we observed transmural fibrotic scarring with extensive fibrosis on irradiated atrial tissue. The findings suggest that this novel circular box-design radiotherapy technique using SABR could be applied to humans after further studies are conducted to confirm safety.


Assuntos
Fibrilação Atrial/radioterapia , Veias Pulmonares/efeitos da radiação , Radiocirurgia/métodos , Animais , Modelos Animais de Doenças , Cães , Estudos de Viabilidade , Masculino , Modelos Animais , Tomografia Computadorizada por Raios X
11.
Int J Radiat Oncol Biol Phys ; 111(3): 658-670, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34144146

RESUMO

PURPOSE: Recently, several studies have reported that low-dose radiation therapy (RT) suppresses the release of proinflammatory cytokines in inflammatory-degenerative disorders, including Alzheimer disease (AD). AD is the most common cause of dementia, and neuroinflammation is one of the major contributing factors in AD pathogenesis. Therefore, low-dose RT may be used clinically for treating AD. However, the appropriate doses, effects, and underlying mechanisms of RT in AD have not been determined. In this study, we aimed to determine the appropriate RT dose and schedule for AD treatment and to investigate the therapeutic effects and mechanisms of low-dose RT in AD. METHODS AND MATERIALS: We first determined the proper dose and schedule for RT in late-stage AD using 8- to 9-month-old 5x Familial AD (5xFAD) mice, a well-known animal model of AD, by comparing the effects of a low total dose with low dose per fraction (LD-LDRT, 5 × 0.6 Gy) with those of a low moderate total dose with conventional dose per fraction (LMD-CDRT, 5 × 2 Gy). RESULTS: LD-LDRT and LMD-CDRT were found to reduce the levels of the proinflammatory cytokines CD54, IL-3, CXCL9/10, and CCL2/4 in the hippocampus of 5xFAD mice. Furthermore, increased microgliosis assessed using Iba-1 and CD68 dual immunostaining was significantly reduced by LD-LDRT and LMD-CDRT in the hippocampus of 5xFAD mice. Moreover, LD-LDRT and LMD-CDRT decreased the amyloid plaque burden in the hippocampus of 5xFAD mice and attenuated their cognitive impairment; these effects persisted for 4 to 5 weeks. CONCLUSIONS: The present study showed that LD-LDRT alleviates cognitive impairments and prevents the accumulation of amyloid plaques by regulating neuroinflammation in the late stage of AD in 5xFAD mice, with an efficacy equivalent to that of LMD-CDRT. Furthermore, the findings suggest that compared with LMD-CDRT, LD-LDRT may facilitate accessible and convenient treatment in clinical trials.

12.
Medicine (Baltimore) ; 100(24): e26338, 2021 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-34128879

RESUMO

ABSTRACT: The purpose of this study is to compare the longitudinal location of endoscopically-defined gross tumor volume (GTV) and positron emission tomography-based metabolic tumor volume (MTV) of esophageal cancer.A retrospective review of medical records was performed of the nine patients who underwent endoscopic placement of fiducial markers for radiotherapy of esophageal squamous cell carcinoma. Endoscopic hemoclips were used as the fiducial markers, and GTV was newly delineated solely based on the locations of the fiducial markers. The standardized uptake value (SUV) threshold corresponding to the superior and inferior borders of GTV was defined as the highest threshold that made MTV reach each border of GTV.The median fixed relative and absolute thresholds were 32% and 3.8, respectively. The coefficient of variation of the threshold values was 0.781 for the fixed relative threshold method and 0.400 for the fixed absolute threshold method, indicating more consistent results from the fixed absolute threshold method. All but two GTV borders were included in MTV with a SUV threshold of 2.5. Esophageal tumors with a maximum SUV > 20 tended to have closer threshold values corresponding to the GTV borders to 2.5 (median 2.8 vs 3.6, P = .069).The fixed absolute threshold method was suitable for determining the MTV threshold for esophageal lesions. A SUV of 2.5 was appropriate for esophageal tumors with a maximum SUV > 20. Endoscopic hemoclips were stable enough for using as the fiducial marker.


Assuntos
Endossonografia , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/patologia , Tomografia por Emissão de Pósitrons , Carga Tumoral , Idoso , Idoso de 80 Anos ou mais , Neoplasias Esofágicas/diagnóstico por imagem , Carcinoma de Células Escamosas do Esôfago/diagnóstico por imagem , Feminino , Marcadores Fiduciais , Fluordesoxiglucose F18 , Humanos , Masculino , Pessoa de Meia-Idade , Compostos Radiofarmacêuticos , Planejamento da Radioterapia Assistida por Computador/métodos , Estudos Retrospectivos
13.
J Infect Public Health ; 14(5): 601-610, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33848890

RESUMO

BACKGROUND: The current health concern to the entire world is the chronic respiratory disease caused by coronavirus 2 (COVID-19). A specific treatment or proper therapy is still lacking, and the investigations from across the world for proper drug/vaccine development towards disease control are in progress. The Coronavirus replication takes place by the conversion of the polypeptide into functional protein and this occurs due to the key enzyme Main protease (Mpro). Therefore, identification of natural and effective Mpro inhibitors could be a safe and promising approach for COVID-19 control. METHODS: The present in silico study evaluates the effect of bioactive compounds found in Eucalyptus and Corymbia species essential oil on Mpro by docking. Molecular docking of the major seven compounds of essential oil (citronellol, alpha-terpineol, eucalyptol, d-limonene, 3-carene, o-cymene, and alpha-pinene) with Mpro was studied by AutoDock 4.2, and the properties were analysed by PreADMET and Biovia Discovery Studio visualizer. RESULTS: The calculated parameters such as binding energy, hydrophobic interactions, and hydrogen bond interactions of 6LU7 (Mpro) with Eucalyptus and Corymbia volatile secondary metabolites represented its scope as an effective therapy option against covid-19. Among the docked compounds, eucalyptol shows the least binding energy without toxicity. CONCLUSIONS: The outcome of this study reported that the essential oil of Eucalyptus and Corymbia species, mainly eucalyptol can be utilized as a potential inhibitor against COVID-19 and also it can be used in its treatment. Hence, further analysis was required to explore its potential application in medicine.


Assuntos
COVID-19 , Óleos Voláteis , Humanos , Simulação de Acoplamento Molecular , Peptídeo Hidrolases , SARS-CoV-2
14.
J Am Heart Assoc ; 10(6): e019072, 2021 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-33660526

RESUMO

Background Noninvasive cardiac radioablation is employed to treat ventricular arrhythmia. However, myocardial changes leading to early-period antiarrhythmic effects induced by high-dose irradiation are unknown. This study investigated dose-responsive histologic, ultrastructural, and functional changes within 1 month after irradiation in rat heart. Methods and Results Whole hearts of wild-type Lewis rats (N=95) were irradiated with single fraction 20, 25, 30, 40, or 50 Gy and explanted at 1 day or 1, 2, 3, or 4 weeks' postirradiation. Microscopic pathologic changes of cardiac structures by light microscope with immunohistopathologic staining, ultrastructure by electron microscopy, and functional evaluation by ECG and echocardiography were studied. Despite high-dose irradiation, no myocardial necrosis and apoptosis were observed. Intercalated discs were widened and disrupted, forming uneven and twisted junctions between adjacent myocytes. Diffuse vacuolization peaked at 3 weeks, suggesting irradiation dose-responsiveness, which was correlated with interstitial and intracellular edema. CD68 immunostaining accompanying vacuolization suggested mononuclear cell infiltration. These changes were prominent in working myocardium but not cardiac conduction tissue. Intracardiac conduction represented by PR and QTc intervals on ECG was delayed compared with baseline measurements. ST segment was initially depressed and gradually elevated. Ventricular chamber dimensions and function remained intact without pericardial effusion. Conclusions Mononuclear cell-related intracellular and extracellular edema with diffuse vacuolization and intercalated disc widening were observed within 1 month after high-dose irradiation. ECG indicated intracardiac conduction delay with prominent ST-segment changes. These observations suggest that early antiarrhythmic effects after cardiac radioablation result from conduction disturbances and membrane potential alterations without necrosis.


Assuntos
Arritmias Cardíacas/radioterapia , Ecocardiografia , Eletrocardiografia , Frequência Cardíaca/fisiologia , Ventrículos do Coração/ultraestrutura , Miocárdio/ultraestrutura , Radiocirurgia/métodos , Animais , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/fisiopatologia , Relação Dose-Resposta à Radiação , Seguimentos , Ventrículos do Coração/efeitos da radiação , Masculino , Microscopia Eletrônica , Ratos , Ratos Endogâmicos Lew , Fatores de Tempo
15.
Eur J Cardiothorac Surg ; 60(1): 74-80, 2021 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-33668061

RESUMO

OBJECTIVES: Surgical resection is the best option for the treatment of early-stage lung cancer. However, older patients are less likely to receive curative treatment. Therefore, we compared long-term survival rates between surgical resection and stereotactic ablative radiotherapy (SABR) for the treatment of early-stage lung cancer in older patients. METHODS: From 2013 to 2016, 272 patients aged ≥75 years with clinical stage I lung cancer underwent surgical resection (n = 191) or SABR (n = 81). A propensity score-matched analysis was performed. Overall survival, cumulative incidence of cancer-related death and recurrence were compared between the 2 groups. RESULTS: In the matched cohort, 48 well-balanced pairs were extracted. An overall survival benefit was associated with surgery (surgery vs SABR = 65.9% vs 40.3%; P = 0.034); however, there was no significant difference in the cumulative incidence of cancer-related death (P = 0.089) or recurrence (P = 0.111) between the 2 groups. Systemic dissemination was the dominant pattern of progression in both groups. The 3-year cumulative incidence of regional recurrence was significantly higher in the SABR group compared to the surgery group (surgery vs SABR = 0% vs 11.4%, P = 0.046). CONCLUSIONS: Surgical resection with mediastinal lymph node dissection provides better long-term survival compared to SABR in older patients with stage I lung cancer. Surgery should be considered for older patients aged ≥75 years who are appropriate candidates for surgery. SABR remains an alternative treatment with comparable cancer-related death and recurrence for patients unsuitable for surgery.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Radiocirurgia , Idoso , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/cirurgia , Recidiva Local de Neoplasia/cirurgia , Estadiamento de Neoplasias , Resultado do Tratamento
16.
Gut ; 70(12): 2249-2260, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33558271

RESUMO

OBJECTIVE: Dysfunctional resolution of intestinal inflammation and altered mucosal healing are essential features in the pathogenesis of inflammatory bowel disease (IBD). Intestinal macrophages are vital in the process of inflammation resolution, but the mechanisms underlying their mucosal healing capacity remain elusive. DESIGN: We investigated the role of the prostaglandin E2 (PGE2) receptor PTGER4 on the differentiation of intestinal macrophages in patients with IBD and mouse models of intestinal inflammation. We studied mucosal healing and intestinal epithelial barrier regeneration in Csf1r-iCre Ptger4fl/fl mice during dextran sulfate sodium (DSS)-induced colitis. The effect of PTGER4+ macrophage secreted molecules was investigated on epithelial organoid differentiation. RESULTS: Here, we describe a subset of PTGER4-expressing intestinal macrophages with mucosal healing properties both in humans and mice. Csf1r-iCre Ptger4fl/fl mice showed defective mucosal healing and epithelial barrier regeneration in a model of DSS colitis. Mechanistically, an increased mucosal level of PGE2 triggers chemokine (C-X-C motif) ligand 1 (CXCL1) secretion in monocyte-derived PTGER4+ macrophages via mitogen-activated protein kinases (MAPKs). CXCL1 drives epithelial cell differentiation and proliferation from regenerating crypts during colitis. Specific therapeutic targeting of macrophages with liposomes loaded with an MAPK agonist augmented the production of CXCL1 in vivo in conditional macrophage PTGER4-deficient mice, restoring their defective epithelial regeneration and favouring mucosal healing. CONCLUSION: PTGER4+ intestinal macrophages are essential for supporting the intestinal stem cell niche and regeneration of the injured epithelium. Our results pave the way for the development of a new class of therapeutic targets to promote macrophage healing functions and favour remission in patients with IBD.

17.
Saudi J Biol Sci ; 28(1): 560-565, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33424339

RESUMO

The dysfunction of left atrial appendage (LAA) is prone to form thrombus when atrial fibrillation (AF) sustained more than 48 h. Traditional 2D-TEE (transesophageal echocardiography) can not accurate evaluate the function of LAA. The purpose of this study is to analyze the relationship of LAA function parameters and thrombus formation in patients with non-valvular atrial fibrillation (NVAF) by real-time three-dimensional transesophageal echocardiography (RT-3D-TEE). High risk patients can be identified according to the characteristics of ultrasonic index in patients with left atrial appendage thrombosis, which has important clinical value and significance in the risk assessment, guiding treatment and judging prognosis. We examined the relationship between the echocardiographic parameters of LAA function and the incidence of thrombus in 102 NVAF patients. They underwent RT-3D-TEE and left atrial appendage thrombus (LAAT)/severe spontaneous echocardiographic contrast (SSEC) was found in 67 patients (thrombus group) but absent in the remaining 35 patients (non-thrombus group). After measured by QLAB software, the LAA functional parameters were significantly associated with LAAT/SEC formation. Univariate analysis indicated that AF time, LAD, LVEF, LAA-OAmax, LAAVmax, LAAVI and LAAEF demonstrated a positive association (P < 0.05). However, logistic regression analysis identified that AF time (OR:1.73, P < 0.05)、LAAEF (OR:4.09, P < 0.01)and LAAVI (OR:3.28, P < 0.01) were independent predictors of LAAT/SSEC. In patients with nonvalvular atrial fibrillation, echocardiographic parameters of LAA function are significantly associated with LAAT/SSEC.

18.
Anticancer Res ; 41(2): 757-764, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33517280

RESUMO

BACKGROUND/AIM: Improvement of the efficacy of radiotherapy for lung cancer and glioblastoma is urgently needed. MATERIALS AND METHODS: We synthesized several novel DNA methyltransferase inhibitors and evaluated their potentials as possible radiosensitizers. Eleven non-nucleoside compounds were synthesized and evaluated along with one known compound using human lung cancer (A549) and glioblastoma (U373MG) cells. Cytotoxicity and radiosensitizing effects were evaluated using clonogenic assay. Sensitizer enhancement ratios at a survival fraction of 0.5 were calculated, and statistical analysis was performed using the ratio paired t-test. The inhibitory effects of three selected compounds on the activity of DNA methyltransferase 1 (DNMT1) and the pharmacokinetic profiles were analyzed. RESULTS: All twelve compounds demonstrated various levels of cytotoxicity. Of the twelve compounds, eleven and eight compounds radiosensitized A549 and U373MG cells, respectively, with at least marginal significance (p<0.10). The sensitizer enhancement ratios in A549 and U373MG ranged 1.166-2.537 and 1.083-1.743 among compounds with radiosensitizing effects, respectively. The three selected compounds inhibited DNMT1 activity by 26.5-78.5%. Elimination half-lives ranged from 0.3 to 1.3 h. CONCLUSION: Novel DNA methyltransferase inhibitors with significant radiosensitizing capacity and improved biostability were synthesized. These materials will serve as a basis for the development of novel radiosensitizers.


Assuntos
Neoplasias Encefálicas/enzimologia , DNA (Citosina-5-)-Metiltransferase 1/metabolismo , Inibidores Enzimáticos/farmacologia , Glioblastoma/enzimologia , Neoplasias Pulmonares/enzimologia , Radiossensibilizantes/farmacologia , Células A549 , Neoplasias Encefálicas/terapia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/efeitos da radiação , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Quimiorradioterapia , DNA (Citosina-5-)-Metiltransferase 1/antagonistas & inibidores , Regulação para Baixo , Inibidores Enzimáticos/síntese química , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Glioblastoma/terapia , Humanos , Neoplasias Pulmonares/terapia , Estrutura Molecular , Radiossensibilizantes/síntese química
19.
Biomaterials ; 266: 120477, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33120198

RESUMO

Radiation esophagitis, the most common acute adverse effect of radiation therapy, leads to unwanted consequences including discomfort, pain, an even death. However, no direct cure exists for patients suffering from this condition, with the harmful effect of ingestion and acid reflux on the damaged esophageal mucosa remaining an unresolved problem. Through the delivery of the hydrogel with stent platform, we aimed to evaluate the regenerative capacity of a tissue-specific decellularized extracellular matrix (dECM) hydrogel on damaged tissues. For this, an esophagus-derived dECM (EdECM) was developed and shown to have superior biofunctionality and rheological properties, as well as physical stability, potentially providing a better microenvironment for tissue development. An EdECM hydrogel-loaded stent was sequentially fabricated using a rotating rod combined 3D printing system that showed structural stability and protected a loaded hydrogel during delivery. Finally, following stent implantation, the therapeutic effect of EdECM was examined in a radiation esophagitis rat model. Our findings demonstrate that EdECM hydrogel delivery via a stent platform can rapidly resolve an inflammatory response, thus promoting a pro-regenerative microenvironment. The results suggest a promising therapeutic strategy for the treatment of radiation esophagitis.


Assuntos
Esofagite , Hidrogéis , Animais , Matriz Extracelular , Humanos , Impressão Tridimensional , Ratos , Stents , Tecidos Suporte
20.
Saudi J Biol Sci ; 27(12): 3228-3234, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33304128

RESUMO

This context was investigated to assess the in vitro antioxidant, anti-diabetic, anti-obesity, and angiotensin-converting enzyme (ACE) inhibition traits of Punica granatum fruits peel extract. Initially, among various extracts tested, aqueous and ethanolic peel extracts depicted the presence of diverse phytoconstituents. In vitro antioxidative properties of peel extracts were determined using standard methodologies. Results showed that aqueous and ethanolic extracts had IC50 values of 471.7 and 509.16 µg/mL, respectively in terms of 1,1,diphenyl 2,2,picrylhydrazyl scavenging. Likewise, IC50 values of aqueous and ethanol extract were obtained as 488.76 and 478.47 µg/mL towards the degradation of hydrogen peroxide. The ethanolic extract exhibited the highest inhibition of α-glucosidase by showing activity of 53.34 ± 2.0 to 15.18 ± 1.4 U/L in a dose dependent manner (100-1000 µg/mL). Ethanolic extract was reported as the most active inhibitor of lipase with an IC50 value of 603.50 µg/mL. Ethanolic extract showed increased inhibition of ACE in a concentration dependent manner (100-1000 µg/mL) with IC50 value of 519.45 µg/mL. Fourier transform-infrared spectrum revealed the availability of various functional groups in the ethanolic extract of peel. Gas chromatography-mass spectrometry chromatogram of peel extract illustrated 23 diversified chemical constituents including 1,2,3,4-butanetetrol, Dimethyl sulfone, 9-octadecenamide, and Pentadecanoic acid as predominant compounds. In summary, P. granatum fruits peel extract revealed promising antioxidant, anti-diabetic, anti-obesity, and anti-hypertensive properties.

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