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1.
Cell Signal ; 115: 111029, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-38163576

RESUMEN

Sirtuin 3 (SIRT3) regulates mitochondrial function as a mitochondrial deacetylase during oxidative stress. However, the specific regulatory mechanism and function of SIRT3 in radioresistant cancer cells are unclear. In this study, we aim to investigate how SIRT3 determines the susceptibility to glucose deprivation and its regulation in p53-based radioresistant head and neck cancer cells. We observed mitochondrial function using two established isogenic radioresistant subclones (HN3R-A [p53 null] and HN3R-B [p53 R282W]) with intratumoral p53 heterogeneity. Cell counting analysis was performed to evaluate cell proliferation and cell death. The correlation between the regulation of SIRT3 and enhancer of zeste homolog 2 (EZH2) was confirmed by immunoblotting and chromatin immunoprecipitation assay. p53-deficient radioresistant cells (HN3R-A) expression reduced SIRT3 levels and increased sensitivity to glucose deprivation due to mitochondrial dysfunction compared to other cells. In these cells, activation of SIRT3 significantly prevented glucose deprivation-induced cell death, whereas the loss of SIRT3 increased the susceptibility to glucose deficiency. We discovered that radiation-induced EZH2 directly binds to the SIRT3 promoter and represses the expression. Conversely, inhibiting EZH2 increased the expression of SIRT3 through epigenetic changes. Our findings indicate that p53-deficient radioresistant cells with enhanced EZH2 exhibit increased sensitivity to glucose deprivation due to SIRT3 suppression. The regulation of SIRT3 by EZH2 plays a critical role in determining the cell response to glucose deficiency in radioresistant cancer cells. Therefore, EZH2-dependent SIRT3 could be used as a predictive biomarker to select treatment options for patients with radiation-resistance.


Asunto(s)
Neoplasias de Cabeza y Cuello , Sirtuina 3 , Humanos , Proteína Potenciadora del Homólogo Zeste 2/metabolismo , Sirtuina 3/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Neoplasias de Cabeza y Cuello/radioterapia , Estrés Oxidativo
2.
Integr Med Res ; 12(3): 100973, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37637186

RESUMEN

Background: The decoction form of herbal medicine (D-HM) is mainly prescribed to patients with allergic rhinitis (AR) in Korean Medicine (KM) clinics in the Republic of Korea; however, it is difficult to conduct clinical trials of D-HM due to regulatory issues. This study investigated the clinical safety and effectiveness of D-HM combination therapy for the treatment of AR by analyzing the AR outpatient data from 17 KM clinics. Methods: This retrospective cohort study included patients who visited KM clinics for AR treatment from January 1, 2021, to March 31, 2022. Cases were collated using structured case report forms and divided into the D-HM with KM usual care group (D-HM group) and the KM usual care group (UC group). Since D-HM therapy could not be randomly assigned to the study population, we used optimal propensity score (PS) matching to investigate the effectiveness and safety of D-HM combination therapy in the treatment of AR. Results: Data from 228 patients were collected. After PS matching, 144 patients were finally analyzed. The total nasal symptom score (TNSS) and mini-rhinoconjunctivitis quality of life questionnaire (mini-RQLQ) were significantly improved in the D-HM group compared with those in the UC group (TNSS: p=0.02; mini-RQLQ: p=0.04). Four patients in the D-HM group experienced minor adverse events that were mild and resolved within 15 days. Conclusions: D-HM combination therapy may be beneficial in the management of symptoms and rhinitis-associated quality of life and potentially useful in clinical practice. However, randomized placebo-controlled clinical trials are required to confirm their effectiveness. Study registration: This study has been registered at Clinical Research Information Service (KCT0007242).

3.
Chemosphere ; 340: 139719, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37549746

RESUMEN

Toxic and carcinogenic metal (loid)s, such arsenic (As) and cadmium (Cd), found in contaminated paddy soils pose a serious danger to environmental sustainability. Their geochemical activities are complex, making it difficult to manage their contamination. Rice grown in Cd and As-polluted soils ends up in people's bellies, where it can cause cancer, anemia, and the deadly itai sickness. Solving this issue calls for research into eco-friendly and cost-effective remediation technology to lower rice's As and Cd levels. This research delves deeply into the origins of As and Cd in paddy soils, as well as their mobility, bioavailability, and uptake mechanisms by rice plants. It also examines the current methods and reactors used to lower As and Cd contamination in rice. Iron-modified biochar (Fe-BC) is a promising technology for reducing As and Cd toxicity in rice, improving soil health, and boosting rice's nutritional value. Biochar's physiochemical characteristics are enhanced by the addition of iron, making it a potent adsorbent for As and Cd ions. In conclusion, Fe-BC's biomembrane properties make them an attractive option for remediating As- and Cd-contaminated paddy soils. More efficient mitigation measures, including the use of biomembrane technology, can be developed when sustainable agriculture practices are combined with these technologies.


Asunto(s)
Arsénico , Oryza , Contaminantes del Suelo , Humanos , Cadmio/análisis , Hierro/química , Arsénico/análisis , Suelo/química , Oryza/química , Medición de Riesgo , Contaminantes del Suelo/análisis
4.
Adv Sci (Weinh) ; 10(24): e2302376, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37357145

RESUMEN

The advancement of non-fullerene acceptors with crescent-shaped geometry has led to the need for polymer donor improvements. Additionally, there is potential to enhance the photovoltaic parameters in high-efficiency organic solar cells (OSCs). The random copolymerization method is a straightforward and effective strategy to further optimize photoactive morphology and enhance device performance. However, finding a suitable third component in terpolymers remains a crucial challenge. In this study, a series of terpolymer donors (PTF3, PTF5, PTF10, PTF20, and PTF50) is synthesized by introducing varying amounts of the trifluoromethyl-substituted unit (CF3) into the PM6 polymer backbone. Even subtle changes in the CF3 content can significantly enhance all the photovoltaic parameters due to the optimized energy levels, molecular aggregation/miscibility, and bulk-heterojunction morphology of the photoactive materials. Thus, the best binary OSC based on the PTF5:Y6-BO achieves an outstanding power conversion efficiency (PCE) of 18.2% in the unit cell and a PCE of 11.6% in the sub-module device (aperture size: 54.45 cm2 ), when using halogen-free solvent o-xylene. This work showcases the remarkable potential of the easily accessible CF3 unit as a key constituent in the construction of terpolymer donors in high-performance OSCs.

5.
J Environ Manage ; 344: 118378, 2023 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-37356332

RESUMEN

Soil erosion has become a worldwide problem that threatens the environment and the future of economic and social development. The purpose of this study is to investigate the contribution of steep slopes and gullies to erosion in high precipitation tropical areas of the Ethiopian highlands. A trapezoidal weir was installed at the head and tail of the gully to monitor the discharge and sediment concentration from 2017 to 2020. Sediment yield and runoff are heavily influenced by the amount and timing of precipitation. The coefficients of variation for total sediment loads ranged from 65.1 to 96.1% at the head and 17.1-78.1% at the tail; the lowest coefficients were found in 2018 and the highest in 2020. Furthermore, 85% of the sediment at the tail comes from the gully, according to the four-year sediment budget. Further, a hysteretic analysis of suspended sediment concentration and runoff revealed that hilly sediment sources are limited (clockwise), then sediment can be transported through the gully via bank failures (counterclockwise). Study findings contributed to a classification of runoff patterns and an investigation of suspended sediment dynamics. In the gully tail, sediment yield was higher than in the head, suggesting gully sediment contributed more to sediment yield than large upland catchments. As a result of the study, we have been able to develop practical recommendations for managing gully erosion in the future.


Asunto(s)
Conservación de los Recursos Naturales , Suelo , Monitoreo del Ambiente , Etiopía , Erosión del Suelo
6.
J Korean Soc Radiol ; 84(3): 596-605, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-37324996

RESUMEN

Purpose: This study aimed to evaluate the US features of the parathyroid glands (PTGs) using surgical specimens of normal PTGs obtained during thyroid surgery. Materials and Methods: This study included 34 normal PTGs from 17 consecutive patients who underwent thyroid surgery between December 2020 and March 2021. All normal PTGs were histologically confirmed by intraoperative frozen-section biopsy for autotransplantation. Surgically resected parathyroid specimens were scanned in sterile normal saline using high-resolution US prior to autotransplantation. The US features of echogenicity (hyperechogenicity or hypoechogenicity), echotexture (homogeneous or heterogeneous), size, and shape (ovoid or round) were retrospectively evaluated. The echogenicity of the three PTGs was compared with that of the thyroid parenchyma of the resected thyroid specimens in two patients. Results: All PTGs showed hyperechogenicity similar to that of gauze soaked in normal saline. Homogeneous hyperechogenicity was observed in 32/34 (94.1%) patients, and the echogenicity of the three PTGs was hyperechoic compared with that of the thyroid parenchyma. The long diameter of the PTGs ranged from 5.1 mm to 9.8 mm (mean, 7.1 mm) and the shape of the PTGs was ovoid in 33/34 (97.1%) patients. Conclusion: The echogenicity of normal PTG specimens was consistently hyperechoic, and the small ovoid homogeneously hyperechoic structure was a characteristic US feature of the PTGs.

7.
Small ; 19(39): e2302418, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37236206

RESUMEN

Despite the optoelectronic similarities between tin and lead halide perovskites, the performance of tin-based perovskite solar cells remains far behind, with the highest reported efficiency to date being ≈14%. This is highly correlated to the instability of tin halide perovskite, as well as the rapid crystallization behavior in perovskite film formation. In this work, l-Asparagine as a zwitterion plays a dual role in controlling the nucleation/crystallization process and improving the morphology of perovskite film. Furthermore, tin perovskites with l-Asparagine show more favorable energy-level matching, enhancing the charge extraction and minimizing the charge recombination, leading to an enhanced power conversion efficiency of 13.31% (from 10.54% without l-Asparagine) with remarkable stability. These results are also in good agreement with the density functional theory calculations. This work not only provides a facile and efficient approach to controlling the crystallization and morphology of perovskite film but also offers guidelines for further improved performance of tin-based perovskite electronic devices.

8.
NPJ Precis Oncol ; 7(1): 46, 2023 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-37210456

RESUMEN

Optimal first-line treatment that enables deeper and longer remission is crucially important for newly diagnosed multiple myeloma (NDMM). In this study, we developed the machine learning (ML) models predicting overall survival (OS) or response of the transplant-ineligible NDMM patients when treated by one of the two regimens-bortezomib plus melphalan plus prednisone (VMP) or lenalidomide plus dexamethasone (RD). Demographic and clinical characteristics obtained during diagnosis were used to train the ML models, which enabled treatment-specific risk stratification. Survival was superior when the patients were treated with the regimen to which they were low risk. The largest difference in OS was observed in the VMP-low risk & RD-high risk group, who recorded a hazard ratio of 0.15 (95% CI: 0.04-0.55) when treated with VMP vs. RD regimen. Retrospective analysis showed that the use of the ML models might have helped to improve the survival and/or response of up to 202 (39%) patients among the entire cohort (N = 514). In this manner, we believe that the ML models trained on clinical data available at diagnosis can assist the individualized selection of optimal first-line treatment for transplant-ineligible NDMM patients.

10.
Sci Total Environ ; 836: 155746, 2022 Aug 25.
Artículo en Inglés | MEDLINE | ID: mdl-35525368

RESUMEN

The soil physical properties are deteriorating due to changing rainfall patterns and intensities, as well as climate change-induced temperature fluctuations. Pot experiments were carried out to examine the impacts of synthesized soil amendments on soil water retention and plant growth. Soil amendments (biochar, polyacrylamide (PAM), and moringa) were used at different rates (0 (control), 2.1, 4.2, and 8.3 g kg-1) to improve the physical properties of the soil. As a result of soil amendment application, it was found that the mean weight diameter of soil aggregate increased by 188% during the 8.3 g kg-1 treatment, forming stable soil particles. Soil water retention improved by up to 128.9% during the 8.3 g kg-1 treatment, and it was analyzed that it was due to the high surface area of biochar, porosity, and high molecular weight of PAM. Pellet treatment increased all plant growth parameters (height, stem diameter, leaf number, and fresh and dry weight) for both beans and maize. The dry weight of beans (C3 plant) and maize (C4 plant) increased by 92.9 and 146.4%, respectively in an 8.3 g kg-1 pot. The soil physical condition was stabilized by the high carbon content of biochar and the improvement of soil coagulation between PAM and moringa. This had a positive effect on the C4 plant. The findings of this study indicate that if the soil amendments are properly mixed and applied based, they will improve soil stability and plant productivity.


Asunto(s)
Carbón Orgánico , Suelo , Carbono , Carbón Orgánico/farmacología , Agua , Zea mays
11.
J Control Release ; 346: 158-168, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35452763

RESUMEN

Therapy-induced senescence (TIS), a common outcome of current cancer therapy, is a known cause of late recurrence and metastasis and thus its eradication is crucial for therapy success. In this study, we introduced a conceptually novel strategy combining radiation-induced apoptosis-targeted chemotherapy (RIATC) with an effective glycolysis inhibitor, 2-deoxy-d-glucose (2DG) to target TIS. RIATC releases cytotoxic payload by amplification, continually increasing TIS, and this can be targeted by 2DG that stimulates an intrinsic apoptotic pathway in senescent cells, the senolysis; the senolytic 2DG also sensitizes cancer cells to chemo/radiation treatment. Anti-tumor efficacy of RIATC was investigated in numerous tumor models, and various cancer types were screened for TIS. Furthermore, in vitro evaluations of molecular markers of senescence, such as senescence-associated ß-galactosidase (SA-ß-Gal) assay, were performed to confirm that TIS was induced by RIATC therapy in MCF-7 cells. The combination therapy with 2DG proved to be effective in MCF-7 tumor-bearing mice that demonstrated feedback amplification of senolysis and successful inhibition of tumor growth. Our findings suggest that RIATC, when given together with 2DG, can overcome therapy-induced senescence and this combination is a promising strategy that enhances the therapeutic benefit of anti-cancer cytotoxic therapy.


Asunto(s)
Antineoplásicos , Caspasa 3 , Doxorrubicina , Animales , Antineoplásicos/farmacología , Apoptosis , Caspasa 3/metabolismo , Desoxiglucosa/uso terapéutico , Doxorrubicina/farmacología , Humanos , Células MCF-7 , Ratones , Péptidos/farmacología
13.
Anal Chim Acta ; 1166: 338573, 2021 Jun 29.
Artículo en Inglés | MEDLINE | ID: mdl-34022993

RESUMEN

Acidic lipids are associated with the regulation of the structure and function of membrane proteins. Therefore, accurate and highly precise analysis of acidic lipids is important for elucidating their biological roles and pathological mechanisms. In this study, an enhanced analytical method for the separation and quantification of acidic lipids, including phosphatidylserine (PS), phosphatidic acid (PA), cardiolipin, and their lyso-derivatives, was developed using nanoflow ultrahigh performance liquid chromatography-electrospray ionisation-tandem mass spectrometry. The separation and mass spectrometry detection of acidic lipids were optimised in terms of peak tailing and time-based separation efficiencies, with carbamate-embedded C18 as the stationary phase, in the presence of an appropriate liquid chromatography solvent modifier. This newly developed method was applied to analyse a lipid extract from porcine brain. A significant increase in the number of acidic lipids identified (176 vs. 134), including intact monolysocardiolipin (17 vs. 4), was observed with the new method compared with conventional C18. The quantification of acidic lipids was validated with plasma standard (NIST SRM 1950) spiked with a number of LPS and PS standards, and acceptable accuracy (<15%) was obtained. The present method was found to be reliable for the acidic lipid analysis based on qualitative results from tissue extract and plasma samples.


Asunto(s)
Plasma , Animales , Cromatografía Líquida de Alta Presión , Cromatografía Liquida , Espectrometría de Masas , Solventes , Porcinos
14.
Artículo en Inglés | MEDLINE | ID: mdl-33991954

RESUMEN

Lipid analysis is a powerful tool that can elucidate the pathogenic roles of lipids in metabolic diseases, and facilitate the development of potential biomarkers. Lipid analysis by large-scale lipidomics requires a high-speed and high-throughput analytical platform. In the present study, a high-speed analytical method for lipid analysis using nanoflow ultrahigh-performance liquid chromatography-electrospray ionisation-tandem mass spectrometry (nUHPLC-ESI-MS/MS) was optimised by investigating the effects of column flow rate, pump flow rate, dwell time, initial binary mobile phase composition, and gradient duration on the separation efficiency of standard lipid mixtures. The minimum gradient time for high-speed lipid separation was determined by examining the time-based separation efficiency and spectral overlap of isobaric lipid species during selected reaction monitoring-based quantification of sphingomyelin and a second isotope of phosphatidylcholine, which differ in molecular weight by only 1 Da. Finally, the optimised nUHPLC-ESI-MS/MS method was applied to analyse 200 plasma samples from patients with liver, gastric, lung, and colorectal cancer to evaluate its performance by measuring previously identified candidate lipid biomarkers. About 73% of the reported marker candidates (6 out of 7 in liver, 5/9 in gastric, 4/6 in lung, and 6/7 in colorectal cancer) could be assigned using the optimised method, supporting its use for high-throughput lipid analysis.


Asunto(s)
Lípidos/sangre , Neoplasias/sangre , Adulto , Anciano , Biomarcadores/sangre , Estudios de Casos y Controles , Cromatografía Líquida de Alta Presión , Femenino , Humanos , Lipidómica , Masculino , Persona de Mediana Edad , Espectrometría de Masas en Tándem
15.
Anal Chem ; 93(11): 4867-4875, 2021 03 23.
Artículo en Inglés | MEDLINE | ID: mdl-33689313

RESUMEN

This study introduces a high-speed screening method for the quantitative analysis of lipoprotein components in human plasma samples using online miniaturized asymmetrical flow field-flow fractionation and electrospray ionization-tandem mass spectrometry (mAF4-ESI-MS/MS). Using an mAF4 channel, high-density lipoproteins and low-density lipoproteins can be fractionated by size at a high speed (<10 min) and directly fed to ESI-MS/MS for the simultaneous screening of targeted lipid species and apolipoprotein A1 (ApoA1). By employing the heated electrospray ionization probe as an ionization source, an mAF4 effluent flow rate of up to a few tens of microliters per minute can be used, which is adequate for direct feeding to MS without splitting the outflow, resulting in a consistent feed rate to MS for stable MS detection. mAF4-ESI-MS/MS was applied to hepatocellular carcinoma (HCC) plasma samples for targeted quantification of 25 lipid biomarker candidates and ApoA1 compared with healthy controls, the results of which were in statistical agreement with the quantified results obtained by nanoflow ultrahigh performance liquid chromatography-tandem mass spectrometry. Moreover, the present method provided the simultaneous detection of changes in lipoprotein size and the relative amount. This study demonstrated the potential of mAF4-ESI-MS/MS as an alternative high-speed screening platform for the top-down analysis of targeted lipoprotein components in patients with HCC, which is applicable to other diseases that involve the perturbation of lipoproteins.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Lipoproteínas , Neoplasias Hepáticas/diagnóstico , Espectrometría de Masa por Ionización de Electrospray , Espectrometría de Masas en Tándem
16.
Cell Signal ; 77: 109820, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33137455

RESUMEN

The manner in which p53 maintains redox homeostasis and the means by which two key metabolic elements, glucose and glutamine, contribute to p53-dependent redox stability remain unclear. To elucidate the manner in which p53 deals with glucose-deprived, reactive oxygen species (ROS)-prone conditions in this regard, two isogenic cancer subclones (HN3R-A and HN3R-B) bearing distinct p53 mutations as an in vitro model of intratumoral p53 heterogeneity were identified. Following cumulative irradiation, the subclones showed a similar metabolic shift to aerobic glycolysis and increasing NADPH biogenesis for cellular defense against oxidative damage irrespective of p53 status. The radioresistant cancer cells became more sensitive to glycolysis-targeting drugs. However, in glucose-deprived and ROS-prone conditions, HN3R-B, the subclone with the original p53 increased the utilization of glutamine by GLS2, thereby maintaining redox homeostasis and ATP. Conversely, HN3R-A, the p53-deficient radioresistant subclone displayed an impairment in glutamine usage and high susceptibility to metabolic stresses as well as ROS-inducing agents despite the increased ROS scavenging system. Collectively, our findings suggest that p53 governs the alternative utilization of metabolic ingredients, such as glucose and glutamine, in ROS-prone conditions. Thus, p53 status may be an important biomarker for selecting cancer treatment strategies, including metabolic drugs and ROS-inducing agents, for recurrent cancers after radiotherapy.


Asunto(s)
Glutamina/metabolismo , Estrés Oxidativo/genética , Proteína p53 Supresora de Tumor/metabolismo , Antineoplásicos/farmacología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Glucosa/farmacología , Glutaminasa/metabolismo , Glutatión/metabolismo , Glucólisis , Neoplasias de Cabeza y Cuello/metabolismo , Neoplasias de Cabeza y Cuello/patología , Humanos , NADP/metabolismo , Oxidación-Reducción , Tolerancia a Radiación , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/genética , Proteína p53 Supresora de Tumor/deficiencia , Proteína p53 Supresora de Tumor/genética
17.
Ann Transl Med ; 8(21): 1363, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-33313108

RESUMEN

BACKGROUND: Clinical diagnosis of post-hepatectomy liver failure (PHLF) can only be made on or after the 5th postoperative day. Biomarker for early diagnosis is considered as a critical unmet need. METHODS: Twenty domestic female crossbreed (Yorkshire-landrace and duroc) pigs underwent sham operation (n=6), 70% (n=7) and 90% (n=7) partial hepatectomy (PH). A comprehensive lipidomic analysis was conducted using sera collected at pre-operation (PO), 14, 30, and 48 h after PH using nanoflow ultrahigh performance liquid chromatography-electrospray ionization-tandem mass spectrometry. RESULTS: Of the 184 quantified lipids, 14 lipids showed significant differences between the two resection groups starting at 30 h after surgery. Four phosphatidylcholine (PC) plasmalogen species (P-16:0/16:0, P-18:0/18:2, P-18:0/20:4, and P-18:0/22:6) and PC 32:2 significantly increased in the 90% PH group while these returned to PO level after 30 h in the 70% PH group, presumably implying the failure markers. In contrast, eight triacylglycerol (TG) species (40:0, 42:1, 42:0, 44:1, 44:2, 46:1, 46:2, and 48:3) and sphingomyelin d18:1/20:0 showed an opposite trend, wherein they significantly decreased in the 90% PH group while these in the 70% PH group were abruptly increased until 30 h but returned to near PO levels at 48 h, implying the recovery markers. Same trends could also be observed in the level of whole lipid classes of PC plasmalogens and TGs, in addition to selected individual lipid species. CONCLUSIONS: Characteristic lipidomic signatures of PHLF could be identified using large animal models. These candidates have a potential to serve as a tool for early diagnosis and may open new paths to the study to overcome PHLF.

18.
Anal Bioanal Chem ; 412(28): 8003-8014, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32918173

RESUMEN

Daily physical exercise is an essential part of life and is required for remaining healthy; it enhances therapeutic efficacy in the elderly and prevents age-related diseases associated with lipid profile alterations, such as cardiovascular disease, diabetes mellitus, and dementia. To more efficiently analyse the lipid profiles and unveil the effect of exercise in aged mice, we optimized our study by examining the effects of using ionization modifiers in the mobile phase and in-source fragmentation of lysophospholipids on the simultaneous analysis of fatty acids (FAs) including hydroxyl fatty acids, glycerophospholipids, sphingolipids, and glycerolipids using nanoflow ultrahigh performance liquid chromatography-electrospray ionization-tandem mass spectrometry. We applied the optimization to investigate the lipidomic plasma alterations in young (7 weeks old) and aged (84 weeks old) mice (C57BL/6) subjected to treadmill exercise. Of the 390 identified lipid species, 159 were quantified to investigate ageing-related lipid species responsive to physical exercise. In particular, circulating lysophosphatidylcholine and lysophosphatidylethanolamine levels showed a significant decrease, and lysophosphatidic acid showed a simultaneous increase with ageing. The saturated FA (16:0 and 18:0) increased with ageing while the unsaturated FA 22:6 decreased. Dihydroxy fatty acid (18:1_2OH) showed an exercise-induced recovery against ageing. It is notable that the levels of five triacylglycerol species significantly increased by as much as threefold with ageing, but their levels largely recovered to those observed in the young mice after exercise. These findings can help understand the influence of ageing on lipid perturbation and the role of physical exercise on lipidomic recovery in response to ageing-associated loss of physical status. Graphical abstract.


Asunto(s)
Envejecimiento/sangre , Cromatografía Líquida de Alta Presión/métodos , Lípidos/sangre , Nanotecnología , Condicionamiento Físico Animal , Espectrometría de Masa por Ionización de Electrospray/métodos , Animales , Ratones , Ratones Endogámicos C57BL
19.
Cells ; 9(8)2020 08 07.
Artículo en Inglés | MEDLINE | ID: mdl-32784606

RESUMEN

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) has attracted attention as a potential candidate for cancer therapy. However, many primary cancers are resistant to TRAIL, even when combined with standard chemotherapy. The mechanism of TRAIL resistance in cancer cells has not been fully elucidated. The TRAIL death receptor (DR) 3'-untranslated region (3'-UTR) is reported to contain AU-rich elements (AREs) that are important for regulating DR mRNA stability. However, the mechanisms by which DR mRNA stability is determined by its 3'-UTR are unknown. We demonstrate that tristetraprolin (TTP), an ARE-binding protein, has a critical function of regulating DR mRNA stability. DR4 mRNA contains three AREs and DR5 mRNA contains four AREs in 3'-UTR. TTP bound to all three AREs in DR4 and ARE3 in DR5 and enhanced decay of DR4/5 mRNA. TTP overexpression in colon cancer cells changed the TRAIL-sensitive cancer cells to TRAIL-resistant cells, and down-regulation of TTP increased TRAIL sensitivity via DR4/5 expression. Therefore, this study provides a molecular mechanism for enhanced levels of TRAIL DRs in cancer cells and a biological basis for posttranscriptional modification of TRAIL DRs. In addition, TTP status might be a biomarker for predicting TRAIL response when a TRAIL-based treatment is used for cancer.


Asunto(s)
Neoplasias/metabolismo , Receptores del Ligando Inductor de Apoptosis Relacionado con TNF/metabolismo , Ligando Inductor de Apoptosis Relacionado con TNF/metabolismo , Tristetraprolina/metabolismo , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias/tratamiento farmacológico , Procesamiento Postranscripcional del ARN
20.
J Chromatogr A ; 1618: 460849, 2020 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-31928769

RESUMEN

Aging refers to the intracellular accumulation of reactive oxygen species that damages proteins, DNA, and lipids. As alterations in lipid metabolism may trigger metabolic disorders and the onset of metabolic diseases, changes in lipid profiles can be closely related to aging. In this study, a comprehensive lipidomic comparison between 4- and 25-month-old mice was performed to investigate age-induced changes in the lipid profiles of mouse serum, kidney, and heart using nanoflow ultrahigh-performance liquid chromatography-electrospray ionization-tandem mass spectrometry. Quantitative analysis of 279 of the 542 identified lipids revealed significant changes upon aging, mainly showing decreased levels in the three types of samples. Exceptionally, most triacylglycerols showed significant increases in heart tissue. The kidney was influenced more by aging than the serum and heart. The highly abundant lipids in each lipid class with significant decreases (> 2-fold, p < 0.01) were lysophosphatidic acid 18:1, lysophosphatidylinositol 20:4, and ceramide d:18:1/24:0 in serum; lysophosphatidylglycerol 16:0 in heart tissue; and eight phosphatidylethanolamines (20:4, 22:6, 36:2, 36:3, 38:4, 38:5, 38:6, 40:6, and 40:7), two cardiolipins (72:7 and 72:8), and lysophosphatidylcholine 18:0 in kidney tissue. The findings indicate the potential of lipidomic analysis to study characteristic age-related lipid changes.


Asunto(s)
Envejecimiento/metabolismo , Riñón/metabolismo , Lipidómica , Lípidos/sangre , Miocardio/metabolismo , Nanotecnología , Reología , Espectrometría de Masas en Tándem/métodos , Animales , Cromatografía Líquida de Alta Presión , Femenino , Metabolismo de los Lípidos , Lípidos/análisis , Ratones Endogámicos C57BL , Análisis de Componente Principal , Estándares de Referencia , Espectrometría de Masa por Ionización de Electrospray/métodos
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