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1.
Sci Rep ; 11(1): 19895, 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34615945

RESUMO

The aim of this study was to develop a robust algorithm to quantify pulse sharpness that can complement the limitations of radial augmentation index (rAIx) and explore the role of this quantitative sharpness index in reflecting vascular aging or arterial stiffness. The pulse sharpness index (PSI) was developed by combining the end point angle and virtual height, and 528 radial pulses were analyzed. The PSI could be uniformly applied to various waveform morphologies, even those with no or vague tidal waves, unlike the rAIx. Significant sex differences were identified in the rAIx and PSI (P < 0.01 for both), and significant age-dependent decreases in the PSI were observed (P < 0.01). In addition, the PSI and age were correlated (r = - 0.550) at least as strong as the rAIx and age (r = 0.532), and the PSI had a significant negative correlation with arterial stiffness (r = - 0.700). Furthermore, the multiple linear regression model for arterial stiffness using the PSI, age, sex and heart rate showed the excellent performance (cross-validated R2 = 0.701), and the PSI was found to have the greatest influence on arterial stiffness. This study confirmed that the PSI could be a quantitative index of vascular aging and has potential for use in inferring arterial stiffness with an advantage over the rAIx.

2.
Atherosclerosis ; 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34607706

RESUMO

BACKGROUND AND AIMS: There are limited data regarding the association between lipoprotein(a) (Lp[a]) and subclinical coronary atherosclerosis. This study investigated the association between Lp(a) and subclinical coronary atherosclerosis detected by coronary computed tomographic angiography (CCTA) in an asymptomatic population. METHODS: We retrospectively analyzed 7201 asymptomatic individuals (mean age 54.4 ± 7.9 years; 65.3% men with no prior history of coronary artery disease who voluntarily underwent CCTA as part of a general health examination). The degree and extent of subclinical coronary atherosclerosis were evaluated by CCTA. Study participants were stratified into quartiles according to their Lp(a) levels (<4.3, 4.3-8.9, 9.0-20.1, and ≥20.2 mg/dL). RESULTS: Of the study participants, any coronary plaque on CCTA was observed in 2557 (35.5%). Specifically, calcified, non-calcified, and mixed plaques were observed in 2411 (33.5%), 363 (5.0%) and 249 (3.5%) participants, respectively. After adjustment for the presence of cardiovascular risk factors, the fourth Lp(a) quartile was significantly associated with any coronary (odds ratio [OR] 1.212; 95% confidence interval [CI] 1.038-1.416), calcified (1.205, 95% CI 1.030-1.410), non-calcified (1.588, 95% CI 1.152-2.189), or mixed (1.674, 95% CI 1.172-2.391) plaque compared with the first Lp(a) quartile. In addition, 442 (6.1%) had significant coronary artery stenosis (≥50% diameter stenosis). The odds ratio for significant stenosis (1.537, 95% CI 1.153-2.048) was higher in the fourth quartile compared with the first quartile. CONCLUSIONS: In this large cross-sectional study with asymptomatic individuals undergoing CCTA, higher Lp(a) level was associated with subclinical coronary atherosclerosis.

3.
Artigo em Inglês | MEDLINE | ID: mdl-34608065

RESUMO

PURPOSE: This study compared the extended depth of focus (EDOF) intraocular lens (IOL) (ZXR00; Tecnis Symfony, Johnson & Johnson Vision, Santa Ana, CA, US) to a novel, higher-order aspheric monofocal IOL (ICB00; Tecnis Eyhance, Johnson & Johnson Vision, Santa Ana, CA, US) which uses the same platform and material. METHODS: Medical records of patients undergoing cataract surgery with ZXR00 or ICB00 implantation between March 2020 and January 2021 and with the data available for the 3-month visit were reviewed. The uncorrected near, intermediate, and distance visual acuity (VA); corrected distance VA; and optical quality parameters were the main outcome measures. RESULTS: Among the 174 enrolled patients, 72 and 102 received the ZXR00 and ICB00, respectively. The average patient ages were 59.6 ±â€Š10.6 (range: 49 to 70) and 65.2 ±â€Š8.2 (range: 45 to 82) years in the ZXR00 and ICB00 groups, respectively, with significantly older patients in the ICB00 group. The other baseline parameters were not different for the 2 groups. Compared to the ICB00 group, the ZXR00 group showed markedly superior near VA (P < 0.05) at 3 months postoperatively. In terms of optical quality, ICB00 was, statistically, significantly superior to ZXR00. CONCLUSIONS: The ZXR00 showed remarkable near vision and defocus curve smoothness, while the ICB00 achieved better optical quality. The 2 IOLs had comparable distance and intermediate vision.

4.
J Hazard Mater ; 423(Pt A): 126992, 2021 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-34474363

RESUMO

The growing consumption of plastic materials has increased hazardous threats to all environmental media, since current plastic waste management methods release microplastics and toxic chemicals. As such, massive generation of plastic derived pollutants leads to significant public health and environmental problems. In this work, an environmentally sound method for valorization of plastic waste is suggested. In detail, pyrolysis of polycarbonate-containing plastic waste such as automotive headlight housing (AHH) was carried out using CO2 as a co-reactant. AHH was chosen as it discharges bisphenol A (BPA) and aromatic compounds. Under CO2 condition, emissions of BPA and its derivatives were suppressed by 14.5% due to gas phase reactions (GPRs) with CO2. Nevertheless, reaction kinetics for GPRs was not significant. To impart the GPRs, catalytic pyrolysis was done using Ni and Co-based catalysts. During catalytic pyrolysis, syngas production was more than tenfold up comparing to pyrolysis without catalyst. The expedited GPRs over catalysts resulted in the enhanced syngas formation. Total concentration of the toxic chemicals from CO2-assisted catalytic pyrolysis of AHH decreased by 86.1% and 66.7% over Ni and Co catalysts, comparing to those from N2 environment.

5.
J Affect Disord ; 295: 291-297, 2021 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-34482061

RESUMO

BACKGROUND: We aimed to investigate the prevalence and associated factors of newly developed depression in patients who underwent craniotomy for brain tumor removal, as well as its effect on long-term mortality. METHODS: Using a nationwide cohort database in South Korea, we included adult patients diagnosed with brain tumors who underwent craniotomy for brain tumor removal from January 1, 2011, to December 31, 2017. We excluded patients with a preoperative history of depression. RESULTS: Among 4,275 patients, 727 (17.0%) patients were newly diagnosed with depression within one year, postoperatively. Two-year all-cause mortality and mortality due to brain cancer occurred in 1,233 (28.8%) and 1,099 (25.7%) patients, respectively. In the multivariable logistic regression model, older age, living in rural areas, newly acquired brain disability, underlying other psychiatric disorders, and longer length of hospital stay were associated with a higher incidence of newly developed depression. In the multivariable Cox regression model, newly acquired depression was associated with a 1.58-fold higher 2-year all-cause mortality compared with that in other patients (hazard ratio: 1.58, 95% confidence interval: 1.38-1.80; P < 0.001). LIMITATION: Lack of information regarding severity and pathologic tumor type. CONCLUSION: Within one follow-up year, 17.0% of patients were newly diagnosed with depression after craniotomy for brain tumor removal. Some factors (old age, living in rural areas, newly acquired brain disability, longer length of hospital stay, and underlying other psychiatric illnesses) could be risk factors for newly diagnosed depression. Furthermore, newly developed depression was associated with an increased 2-year all-cause mortality.

6.
J Neurosurg ; : 1-5, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34479201

RESUMO

OBJECTIVE: The lateral spread response (LSR) is an aberrant electrophysiological response in which a stimulus on one branch of the facial nerve spills over to other branches of the nerve, which can be captured by electrodes near each branch. The authors performed this study to evaluate the prognostic value of the follow-up LSR with a sufficient time interval from intraoperative LSR (IO-LSR) after microvascular decompression (MVD) for hemifacial spasm (HFS), excluding the interference of various intraoperative situations. METHODS: A total of 247 patients treated with MVD for HFS between June 2011 and March 2019 were enrolled in this study. The IO-LSR was routinely evaluated in all patients. The LSR was checked again on postoperative day (POD) 2 after surgery (POD2-LSR). A total of 228 patients (92.3%) were considered cured at the last clinical follow-up. RESULTS: The IO-LSR disappeared in 189 patients (76.5%), and among them, 181 patients (95.8%) were cured 1 year after surgery. The POD2-LSR disappeared in 193 patients (78.1%), and 185 patients (95.9%) among them were cured. Among the 189 patients in which the IO-LSR disappeared, the POD2-LSR reappeared in 26 patients (13.8%). In contrast, the POD2-LSR disappeared in 30 (51.7%) of 58 patients for whom the IO-LSR continued at the end of surgery. When classified into groups according to the status of the IO-LSR and POD2-LSR, in the group of patients in whom both LSRs disappeared, the cure rate was 98.2%, which was significantly higher than that of the other 3 groups (p < 0.05, Cochran-Armitage trend test). The use of both LSRs was found to be significantly associated with better predictability (p < 0.05, McNemar's test). CONCLUSIONS: Postoperative follow-up LSR examination may be beneficial in predicting clinical outcomes after MVD for HFS, especially when considered together with IO-LSR.

7.
Braz J Anesthesiol ; 2021 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-34560114

RESUMO

BACKGROUND: The precise underlying mechanism of antioxidant effects of dexmedetomidine-induced neuroprotection against cerebral ischemia has not yet been fully elucidated. Activation of Nuclear factor erythroid 2-related factor (Nrf2) and Heme Oxygenase-1 (HO-1) represents a major antioxidant-defense mechanism. Therefore, we determined whether dexmedetomidine increases Nrf2/HO-1 expression after global transient cerebral ischemia and assessed the involvement of Protein Kinase C (PKC) in the dexmedetomidine-related antioxidant mechanism. METHODS: Thirty-eight rats were randomly assigned to five groups: sham (n = 6), ischemic (n = 8), chelerythrine (a PKC inhibitor; 5 mg.kg-1 IV administered 30 min before cerebral ischemia) (n = 8), dexmedetomidine (100 µg.kg-1 IP administered 30 min before cerebral ischemia (n = 8), and dexmedetomidine + chelerythrine (n = 8). Global transient cerebral ischemia (10 min) was applied in all groups, except the sham group; histopathologic changes and levels of nuclear Nrf2 and cytoplasmic HO-1 were examined 24 hours after ischemia insult. RESULTS: We found fewer necrotic and apoptotic cells in the dexmedetomidine group relative to the ischemic group (p < 0.01) and significantly higher Nrf2 and HO-1 levels in the dexmedetomidine group than in the ischemic group (p < 0.01). Additionally, chelerythrine co-administration with dexmedetomidine attenuated the dexmedetomidine-induced increases in Nrf2 and HO-1 levels (p < 0.05 and p < 0.01, respectively) and diminished its beneficial neuroprotective effects. CONCLUSION: Preischemic dexmedetomidine administration elicited neuroprotection against global transient cerebral ischemia in rats by increasing Nrf2/HO-1 expression partly via PKC signaling, suggesting that this is the antioxidant mechanism underlying dexmedetomidine-mediated neuroprotection.

8.
Org Lett ; 2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34553933

RESUMO

The design, synthesis, and validation of 3-aminobenzyne precursors induced by C-(sp2)-to-N 1,3-aza-Brook rearrangement have been achieved, allowing access to diverse aniline derivatives. Through crossover experiments, we demonstrated the intramolecular mechanism of 1,3-C-to-N silyl transfer. To gain insight into the regioselectivity observed in the reactions, we performed density functional theory calculations. Finally, the method was applied to the synthesis of xylanigripones A in five linear steps in an overall yield of 30%.

9.
Support Care Cancer ; 2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34554281

RESUMO

PURPOSE: We aimed to investigate the prevalence of quality-of-life deterioration and associated factors in patients who underwent craniotomies for brain tumor removal. Additionally, we examined whether deteriorating quality of life after surgery might affect mortality. METHODS: As a national population-based cohort study, data were extracted from the National Health Insurance Service database of South Korea. Adult patients (≥ 18 years old) who underwent craniotomy for excision of brain tumors after diagnosis of malignant brain tumor between January 1, 2011, and December 31, 2017, were included in this study. RESULTS: A total of 4852 patients were included in the analysis. Among them, 2273 patients (46.9%) experienced a deterioration in quality of life after surgery. Specifically, 595 (12.3%) lost their jobs, 1329 (27.4%) experienced decreased income, and 844 (17.4%) patients had newly acquired disabilities. In the multivariable Cox regression model, a lower quality of life was associated with a 1.41-fold higher 2-year all-cause mortality (hazard ratio: 1.41, 95% confidence interval: 1.27-1.57; P < 0.001). Specifically, newly acquired disability was associated with 1.80-fold higher 2-year all-cause mortality (hazard ratio: 1.80, 95% confidence interval: 1.59-2.03; P < 0.001), while loss of job (P = 0.353) and decreased income (P = 0.599) were not significantly associated. CONCLUSIONS: At 1-year follow-up, approximately half the patients who participated in this study experienced a deterioration in the quality-of-life measures of unemployment, decreased income, and newly acquired disability after craniotomy for excision of brain tumors. Newly acquired disability was associated with increased 2-year all-cause mortality.

10.
J Hazard Mater ; 416: 125845, 2021 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-34492798

RESUMO

Aflatoxins (AFs) are the extremely hazardous metabolites (carcinogens) that are sporadically observed in crops, and these toxic chemicals are indeed lethal to the health of living organisms including human beings. Thus, AF contaminated food waste needs to be disposed as an environmentally benign way, not releasing it into the environment. This study offered a sustainable disposal and valorization platform for AF contaminated food. Peanut was used as a model food waste, because AF is readily appeared in the peanut during its harvesting, cultivation, storage, transportation process. As the valorization platform, non-catalytic transesterification of AF contaminated peanut was employed to convert it to biodiesel (BD). From the process, lipid in AF contaminated peanut is converted into BD (95.2 wt% yield) at 365°C for 1 min. Since the boiling points of BD and AF are significantly different, this process could also resolve the separation problem of AF (180 °C) from BD (≥ 330 °C) during the transesterification reaction. As a comparison study, alkali-catalyzed reaction was done. The alkali-catalyzed one required a pretreatment process to extract peanut oil for transesterification. The highest yield was 67.8 wt% yield after 6 h of reaction at 65 °C.


Assuntos
Aflatoxinas , Eliminação de Resíduos , Arachis , Biocombustíveis , Esterificação , Alimentos , Humanos
11.
Chem Asian J ; 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34553505

RESUMO

Interleukin-33 (IL-33) is an epithelial-derived cytokine that plays an important role in immune-mediated diseases such as asthma, atopic dermatitis, and rheumatoid arthritis. Although IL-33 is considered a potential target for the treatment of allergy-related diseases, no small molecule that inhibits IL-33 has been reported. Based on the structure-activity relationship and in vitro 2D NMR studies employing 15 N-labeled IL-33, we identified that the oxazolo[4,5-c]-quinolinone analog 7 c binds to the interface region of IL-33 and IL-33 receptor (ST2), an orphan receptor of the IL-1 receptor family. Compound 7 c effectively inhibited the production of IL-6 in human mast cells in a dose-dependent manner. Compound 7 c is the first low molecular weight IL-33 inhibitor and may be used as a prototype molecule for structural optimization and investigation of the IL-33/ST2 signaling pathway.

12.
Bioresour Technol ; 341: 125858, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34523588

RESUMO

Global warming increases a chance of eutrophication, and such fact offers that unhygienic organic waste materials (OWMs) in water must be treated. Hence, this study laid emphasis on the thermal-chemical (pyrolysis) process to establish a rapid valorization platform for OWMs. Indeed, OWMs were collected from the eutrophication site, and OWMs were mainly comprised of lignocellulosic biomass, microalgae (cyanobacteria) and the diverse types of bacteria (commonly observed from livestock waste). In an attempt to offer more sustainable valorization route for OWMs, CO2 was used as a raw material in pyrolysis process. From the CO2-assisted pyrolysis, the conversion of CO2 and OWMs into gaseous fuel (CO) was observed. A cheap Ni-based catalyst was used in pyrolysis of OWMs as a strategic practice to promote conversion of CO2 into CO. Indeed, syngas production (38 %) was enhanced from catalytic pyrolysis over Ni/SiO2 under CO2 condition as compared to inert condition (N2).


Assuntos
Dióxido de Carbono , Dióxido de Silício , Catálise , Eutrofização , Pirólise
13.
Inflammopharmacology ; 29(5): 1475-1486, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34468900

RESUMO

Novel treatment strategies are urgently required for osteoarthritis (OA). Palmitoylethanolamide (PEA) is a naturally occurring fatty acid amide with analgesic and anti-inflammatory effects. We aimed to examine its effect on OA and elucidate the molecular mechanism of actions in monosodium iodoacetate (MIA)-induced OA Sprague-Dawley rats. The experimental animals were divided into normal control group (injected with saline + treated with phosphate-buffered saline (PBS), NOR), control group (injected with MIA + treated with PBS, CON), 50 or 100 mg/kg body weight (BW)/day PEA-treated group (injected with MIA + treated with 50 or 100 mg of PEA/kg BW/day, PEA50 or PEA100), and positive control group (injected with MIA + treated with 6 mg of diclofenac/kg BW/day, DiC). The changes in blood parameters, body parameters, gene expression of inflammatory mediators and cytokines, knee thickness, and joint tissue were observed. Oral administration of PEA had no adverse effects on the BW, liver, or kidneys. PEA reduced knee joint swelling and cartilage degradation in MIA-induced OA rats. The serum levels of leukotriene B4, nitric oxide, tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and prostaglandin E2 considerably reduced in the PEA100 group compared with those in the CON group. In the synovia of knee joints, the mRNA expression of iNOS, 5-Lox, Cox-2, Il-1ß, Tnf-α, and Mmp-2, -3, -9, and -13 apparently increased with MIA administration. Meanwhile, Timp-1 mRNA expression apparently decreased in the CON group but increased to the normal level with PEA treatment. Thus, PEA can be an effective therapeutic agent for OA.

14.
Appl Clin Inform ; 12(4): 757-767, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34380168

RESUMO

BACKGROUND: Diabetes mellitus (DM) is an important public health concern in Singapore and places a massive burden on health care spending. Tackling chronic diseases such as DM requires innovative strategies to integrate patients' data from diverse sources and use scientific discovery to inform clinical practice that can help better manage the disease. The Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM) was chosen as the framework for integrating data with disparate formats. OBJECTIVE: The study aimed to evaluate the feasibility of converting Singapore based data source, comprising of electronic health records (EHR), cognitive and depression assessment questionnaire data to OMOP CDM standard. Additionally, we also validate whether our OMOP CDM instance is fit for the purpose of research by executing a simple treatment pathways study using Atlas, a graphical user interface tool to conduct analysis on OMOP CDM data as a proof of concept. METHODS: We used de-identified EHR, cognitive, and depression assessment questionnaires data from a tertiary care hospital in Singapore to convert it to version 5.3.1 of OMOP CDM standard. We evaluate the OMOP CDM conversion by (1) assessing the mapping coverage (that is the percentage of source terms mapped to OMOP CDM standard); (2) local raw dataset versus CDM dataset analysis; and (3) Implementing Harmonized Intrinsic Data Quality Framework using an open-source R package called Data Quality Dashboard. RESULTS: The content coverage of OMOP CDM vocabularies is more than 90% for clinical data, but only around 11% for questionnaire data. The comparison of characteristics between source and target data returned consistent results and our transformed data did not pass 38 (1.4%) out of 2,622 quality checks. CONCLUSION: Adoption of OMOP CDM at our site demonstrated that EHR data are feasible for standardization with minimal information loss, whereas challenges remain for standardizing cognitive and depression assessment questionnaire data that requires further work.

15.
Endocrinol Metab (Seoul) ; 36(4): 855-864, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34376042

RESUMO

BACKGROUND: Several studies have reported that abdominal fat and muscle changes occur in diabetic patients. However, there are few studies about such changes among prediabetic patients. In this study, we evaluated the differences in abdominal fat and muscles based on abdominopelvic computed tomography in prediabetic and diabetic subjects compared to normal subjects. METHODS: We performed a cross-sectional study using health examination data from March 2014 to June 2019 at Ulsan University Hospital and classified subjects into normal, prediabetic, and diabetic groups. We analyzed the body mass index corrected area of intra-abdominal components among the three groups using inverse probability treatment weighting (IPTW) analysis. RESULTS: Overall, 8,030 subjects were enrolled; 5,137 (64.0%), 2,364 (29.4%), and 529 (6.6%) subjects were included in the normal, prediabetic, and diabetic groups, respectively. After IPTW adjustment of baseline characteristics, there were significant differences in log visceral adipose tissue index (VATI; 1.22±0.64 cm2/[kg/m2] vs. 1.30±0.63 cm2/[kg/m2] vs. 1.47±0.64 cm2/[kg/m2], P<0.001) and low-attenuation muscle index (LAMI; 1.02±0.36 cm2/[kg/m2] vs. 1.03±0.36 cm2/[kg/m2] vs. 1.09±0.36 cm2/[kg/m2], P<0.001) among the normal, prediabetic, and diabetic groups. Prediabetic subjects had higher log VATI (estimated coefficient= 0.082, P<0.001), and diabetic subjects had higher log VATI (estimated coefficient=0.248, P<0.001) and LAMI (estimated coefficient=0.078, P<0.001) compared to normal subjects. CONCLUSION: Considering that VATI and LAMI represented visceral fat and lipid-rich skeletal muscle volumes, respectively, visceral obesity was identified in both prediabetic and diabetic subjects compared to normal subjects in this study. However, intra-muscular fat infiltration was observed in diabetic subjects only.

16.
Molecules ; 26(16)2021 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-34443392

RESUMO

Thymic stromal lymphopoietin (TSLP) plays an important role in the pathophysiology of various allergic diseases that are mediated by T helper cell type-2 (Th2) responses, including asthma and atopic dermatitis. The primary focus of this study was the identification of potent inhibitors of the TSLP signaling pathway for potential therapeutic use. The 80% methanol extract of Machilus thunbergii bark significantly inhibited the signal transducer and activator of transcription 5 (STAT5) phosphorylation in human mast cell (HMC)-1 cells. Through activity-guided isolation, three lignans (1-3) were obtained and identified as (+)-galbelgin (1), meso-dihydroguaiaretic acid (2), and machilin A (3). Among them, two lignans (1 and 2) significantly inhibited STAT5 phosphorylation and TSLP/TSLPR interaction, as determined by ELISA. Our results indicated that lignans isolated from M. thunbergii are a promising resource for the treatment of allergic diseases.


Assuntos
Citocinas/antagonistas & inibidores , Lauraceae/química , Lignanas/farmacologia , Linhagem Celular , Fosforilação/efeitos dos fármacos , Casca de Planta/química , Fator de Transcrição STAT5/metabolismo , Células Th2/efeitos dos fármacos
17.
Int J Nanomedicine ; 16: 5039-5052, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34335025

RESUMO

Background: Thermal-responsive self-assembled elastin-like polypeptide (ELP)-based nanoparticles are an emerging platform for controlled delivery of therapeutic peptides, proteins and small molecular drugs. The antitumor effect of bioengineered chimeric polypeptide AP1-ELP-KLAK containing an interleukin-4 receptor (IL-4R) targeting peptide and pro-apoptotic peptide (KLAKLAK) was evaluated in glioblastoma (GBM) in vitro and in vivo. Methods and Results: Herein, the therapeutic effect of AP1-ELP-KLAK was tested in advanced, and less curable glioblastoma cells with higher expression of IL-4R. Glioblastoma cell lines stably expressing different reporter systems i.e., caspase-3 sensor (surrogate marker for cellular apoptosis) or effluc/enhanced firefly luciferase (cellular viability) were established to measure cell death non-invasively. Bioluminescence imaging (BLI) of D54/effluc and U97MG/effluc treated with AP1-ELP-KLAK exhibited higher cell death up to 2~3-fold than the control. Treatment with AP1-ELP-KLAK resulted in time-dependent increase of caspase-3 sensor BLI activity in D54/C cells and D54/C tumor-bearing mice. Intravenous injection of AP1-ELP-KLAK dramatically reduced tumor growth by inducing cellular apoptosis in D54/effluc tumor-bearing mice. Further, the immuno-histological examination of the excised tumor tissue confirmed the presence of apoptotic cells as well as caspase-3 activation. Conclusion: Collectively, AP1-ELP-KLAK effectively induced cellular apoptosis of glioblastoma cells and non-invasive imaging provides a window for real-time monitoring of anti-tumor effect with the provision of improving therapeutic efficacy in a glioblastoma mice model.


Assuntos
Glioblastoma , Animais , Linhagem Celular Tumoral , Glioblastoma/tratamento farmacológico , Humanos , Camundongos , Peptídeos , Receptores de Interleucina-4
18.
Am J Cardiol ; 158: 30-36, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34462052

RESUMO

Limited data exist regarding the association between right bundle branch block (RBBB) and subclinical coronary atherosclerosis. This study investigated the influence of RBBB on subclinical coronary atherosclerosis detected by coronary computed tomographic angiography (CCTA) in an asymptomatic population. We retrospectively analyzed 7,205 asymptomatic individuals (mean age 54.4 ± 7.9 years and 4,695 men [65.2%]) with no prior history of coronary artery disease who voluntarily underwent CCTA and 12-lead electrocardiographic evaluation as part of a general health examination. The degree and extent of subclinical coronary atherosclerosis were evaluated by CCTA, and ≥50% diameter stenosis was defined as significant. The association between RBBB and subclinical coronary atherosclerosis was determined by logistic regression and propensity score matching analyses. Of study participants, 116 (1.6%) had RBBB. After adjustment for cardiovascular risk factors, there were no statistically significant differences in the adjusted odds ratios of RBBB for any atherosclerotic plaque (0.87, 95% confidence interval [CI] 0.57 to 1.32), calcified plaque (0.78, 95% CI 0.51 to 1.19), noncalcified plaque (1.44, 95% CI 0.77 to 2.69), mixed plaque (1.12, 95% CI 0.52 to 2.39), and significant coronary artery stenosis (0.92, 95% CI 0.48 to 1.74). Similarly, in the 5: 1 propensity score-matched population (n = 696), there were no statistically significant differences in the odds ratios for any subclinical coronary atherosclerosis between participants with and without RBBB (p for all >0.05). In conclusion, through this large cross-sectional study of asymptomatic individuals who underwent CCTA and electrocardiography evaluation, individuals with RBBB were not associated with an increased risk of subclinical coronary atherosclerosis compared with those without RBBB.

19.
Int J Mol Sci ; 22(15)2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34360546

RESUMO

Promyelocytic leukemia (PML) protein is the core component of subnuclear structures called PML nuclear bodies that are known to play important roles in cell survival, DNA damage responses, and DNA repair. Fanconi anemia (FA) proteins are required for repairing interstrand DNA crosslinks (ICLs). Here we report a novel role of PML proteins, regulating the ICL repair pathway. We found that depletion of the PML protein led to the significant reduction of damage-induced FANCD2 mono-ubiquitination and FANCD2 foci formation. Consistently, the cells treated with siRNA against PML showed enhanced sensitivity to a crosslinking agent, mitomycin C. Further studies showed that depletion of PML reduced the protein expression of FANCA, FANCG, and FANCD2 via reduced transcriptional activity. Interestingly, we observed that damage-induced CHK1 phosphorylation was severely impaired in cells with depleted PML, and we demonstrated that CHK1 regulates FANCA, FANCG, and FANCD2 transcription. Finally, we showed that inhibition of CHK1 phosphorylation further sensitized cancer cells to mitomycin C. Taken together, these findings suggest that the PML is critical for damage-induced CHK1 phosphorylation, which is important for FA gene expression and for repairing ICLs.


Assuntos
Quinase 1 do Ponto de Checagem/metabolismo , Proteína do Grupo de Complementação A da Anemia de Fanconi/metabolismo , Proteína do Grupo de Complementação D2 da Anemia de Fanconi/metabolismo , Proteína do Grupo de Complementação G da Anemia de Fanconi/metabolismo , Anemia de Fanconi/patologia , Regulação da Expressão Gênica , Quinase 1 do Ponto de Checagem/genética , Dano ao DNA , Reparo do DNA , Anemia de Fanconi/genética , Anemia de Fanconi/metabolismo , Proteína do Grupo de Complementação A da Anemia de Fanconi/genética , Proteína do Grupo de Complementação D2 da Anemia de Fanconi/genética , Proteína do Grupo de Complementação G da Anemia de Fanconi/genética , Células HeLa , Humanos , Fosforilação , Ubiquitinação
20.
Am J Hematol ; 96(11): 1441-1449, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34390504

RESUMO

Despite the proven efficacy of anti-T-cell or antithymocyte globulin (ATG) for chronic graft-versus-host disease (GVHD) prevention in transplantation from an unrelated donor, dosing protocols and the effects of ATG on relapse and infection remain controversial. In the setting of transplantation from an HLA-matched sibling (MSD-T), few randomized studies have been conducted. We conducted a prospective, single-center, open-label, randomized study of low-dose thymoglobulin (2.5 mg/kg) for chronic GVHD prevention. A total of 120 patients with acute leukemia were randomly assigned in a 1:1 ratio. After a median follow-up of 27 months, the cumulative incidence of chronic GVHD in the ATG and non-ATG groups was 25.0% and 65.4% (p < 0.001), respectively. The ATG group had an increased relapse rate compared with the non-ATG-group (20.0% vs. 9.3%; p = 0.055), with risks that differed according to cytogenetic subgroup (high-risk, 29.6% vs. 9.3%, p = 0.042; non-high-risk, 12.2% vs. 9.2%, p = 0.596). Chronic GVHD-free and relapse-free survival (cGRFS) was higher in the ATG group (46.7% vs. 19.4%; p = 0.070), and the difference was significant in a cytogenetic non-high-risk subgroup (45.5% vs. 0%; p = 0.038). No differences were observed in other survival outcomes. Improved physical components in quality-of-life scores were observed in the ATG group at 12 months after transplantation. A higher rate of Epstein-Barr virus reactivation was observed in the ATG group (21.8% vs. 5.1%; p = 0.013), whereas no between-group differences for other complications. In conclusion, the low-dose thymoglobulin effectively prevented chronic GVHD in MSD-T, resulting in improvement in quality-of-life and cGRFS, whereas the necessity of caution for high-risk acute leukemia.

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