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2.
Methods Mol Biol ; 2759: 63-68, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38285139

RESUMEN

Stevia rebaudiana Bert. is a plant that contains noncaloric sweeteners highly appreciated in the food industry. However, there is a high demand for propagules to establish commercial plantations, and the conventional reproduction types for this species are inefficient. Micropropagation is a technique that allows obtaining a large number of plants and can be used to meet the demand in the field. However, it requires in vitro propagation techniques such as temporary immersion systems (SIT) to increase yield and reduce production costs. This chapter describes an effective protocol for the large-scale micropropagation of S. rebaudiana using a TIS.


Asunto(s)
Stevia , Reproducción
3.
Methods Mol Biol ; 2759: 97-104, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38285143

RESUMEN

Chayote (Sechium edule) belongs to the Cucurbitaceae family, an important family at the nutritional and medicinal levels, that has been covering international markets. Having vigorous and healthy plants is important for producers, who are very interested in cultivating chayote plants obtained from in vitro tissue culture in their orchards. Bioreactors have become an alternative with high potential for plant propagation, showing significant advantages over micropropagation in semisolid medium, by generating more plant material, larger, and more vigorous. In this chapter, a micropropagation protocol of S. edule in RITA® bioreactors is reported.


Asunto(s)
Reactores Biológicos , Cucurbitaceae , Genes de Plantas , Estado de Salud
4.
Methods Mol Biol ; 2759: 167-181, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38285149

RESUMEN

Shoots from European chestnut and hybrids of European and Asian chestnuts can be efficiently proliferated in liquid medium by temporary immersion (TIS) using RITA® and Plantform™ bioreactors. The main challenges of applying TIS to these species were the lack of growth and hyperhydricity; problem solutions included the manipulation of the hormone concentration, the explant type, immersion frequency, and a support for maintaining shoots in a vertical position. After protocol optimization, explants cultured by TIS produced more rootable shoots than explants growing in semisolid medium, enabling increased number of rooted and acclimatable shoots. In this chapter, we will describe the protocols for proliferating chestnut by TIS in RITA® and Plantform™ bioreactors, together with tips for avoiding the main pitfalls of the technique. The strategies applied to chestnut can be useful for culturing other woody plants in bioreactors.


Asunto(s)
Reactores Biológicos , Inmersión , Nueces , Madera , Proliferación Celular
5.
Biol Trace Elem Res ; 202(3): 1203-1211, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37335443

RESUMEN

The toxic effects of heavy metals are drastic, including accumulation. Fish species are important bio-indicators of heavy metal pollution in aquatic bodies. The current study aimed to assess the seasonal variation of heavy metals in the vital organs of mostly consumed fishes in River Jhelum, Pakistan. Samples of fish, including Wallago attu (Malhi), Rita rita (Khagga), and Mystus seenghala (Singhari), were collected from four different sites, i.e., Khushab, Muhammad Wala (M. Wala), 8.R.D and Rasool barrage during summer and winter seasons. Heavy metals such as iron (Fe), lead (Pb), chromium (Cr), cobalt (Co) and Cadmium (Cd) were estimated through acid digestion and spectrometric analysis. Results showed a significantly higher (P < 0.05) amount of these metals in the liver, followed by the kidneys of fish species. There were seasonal variations in the absorption of these metals as well. Cr (11.71) and Fe (58.66) were detected in higher amounts in Khagga which showed the greatest affinity for certain metals in some cases. In contrast, Singhari showed the greatest affinity to other metals in other cases. Comparative analysis revealed that there was a highly significant (P < 0.05) difference for the accumulation of almost all metals in both seasons and summer had the highest concentration of Cd, Pb, Co, Cr and Fe as compared to winter in all four sampling stations in the case of kidney and liver of all the three fishes. Elevated levels of heavy metals were detected in the summer due to increased temperature. Heavy metals found in the River Jhelum may demonstrate that metals can significantly affect the fish species.


Asunto(s)
Bagres , Metales Pesados , Contaminantes Químicos del Agua , Animales , Estaciones del Año , Cadmio/análisis , Pakistán , Ríos/química , Plomo/análisis , Contaminantes Químicos del Agua/análisis , Metales Pesados/análisis , Cromo/análisis , Peces , Monitoreo del Ambiente/métodos
6.
Autism ; 28(5): 1297-1304, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38155361

RESUMEN

LAY ABSTRACT: It is important to diagnose autism spectrum disorder at an early age and to start an early intervention program without delay. In this study, we aimed to validate the Rapid Interactive Screening Test for Autism in Toddlers (RITA-T) in a group of Turkish children and found that the RITA-T which has been shown to be a valid and reliable screening test for 18- to 36-month-old children in studies conducted in different countries, is also valid in Turkish children. Similar to previous studies, our results showed that the RITA-T has good sensitivity and specificity in distinguishing children with autism spectrum disorder. We think that our study will contribute to the timely initiation of early intervention programs for many children with autism by enabling a valid test to be used in screening programs.


Asunto(s)
Trastorno del Espectro Autista , Sensibilidad y Especificidad , Humanos , Turquía , Masculino , Preescolar , Femenino , Lactante , Trastorno del Espectro Autista/diagnóstico , Reproducibilidad de los Resultados , Tamizaje Masivo/métodos
7.
Nan Fang Yi Ke Da Xue Xue Bao ; 43(5): 710-717, 2023 May 20.
Artículo en Chino | MEDLINE | ID: mdl-37313811

RESUMEN

OBJECTIVE: To screen for small molecular compounds with selective inhibitory activity against cutaneous melanoma cells with BAP1 deletion. METHODS: Cutaneous melanoma cells expressing wild-type BAP1 were selected to construct a BAP1 knockout cell model using CRISPR-Cas9 system, and small molecules with selective inhibitory activity against BAP1 knockout cells were screened from a compound library using MTT assay. Rescue experiment was carried out to determine whether the sensitivity of BAP1 knockout cells to the candidate compounds was directly related to BAP1 deletion. The effects of the candidate compounds on cell cycle and apoptosis were detected with flow cytometry, and the protein expressions in the cells were analyzed with Western blotting. RESULTS: The p53 activator RITA from the compound library was shown to selectively inhibit the viability of BAP1 knockout cells. Overexpression of wild-type BAP1 reversed the sensitivity of BAP1 knockout cells to RITA, while overexpression of the mutant BAP1 (C91S) with inactivated ubiquitinase did not produce any rescue effect. Compared with the control cells expressing wild-type BAP1, BAP1 knockout cells were more sensitive to RITA-induced cell cycle arrest and apoptosis (P < 0.0001) and showed an increased expression of p53 protein, which was further increased by RITA treatment (P < 0.0001). CONCLUSION: Loss of BAP1 results in the sensitivity of cutaneous melanoma cells to p53 activator RITA. In melanoma cells, the activity of ubiquitinase in BAP1 is directly related to their sensitivity to RITA. An increased expression of p53 protein induced by BAP1 knockout is probably a key reason for RITA sensitivity of melanoma cells, suggesting the potential of RITA as a targeted therapeutic agent for cutaneous melanoma carrying BAP1-inactivating mutations.


Asunto(s)
Melanoma , Neoplasias Cutáneas , Humanos , Proteína p53 Supresora de Tumor , Apoptosis , División Celular , Proteínas Supresoras de Tumor/genética , Ubiquitina Tiolesterasa/genética
8.
Plants (Basel) ; 12(12)2023 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-37375856

RESUMEN

The conservation of the genetic resources of old trees is crucial to their ecological role but is extremely difficult, especially for oak species (Quercus spp.) displaying recalcitrance in seed and vegetative propagation methods. Our study aimed to assess the regenerative potential of Quercus robur trees of different ages (up to 800 years) during micropropagation. We also aimed to determine how in vitro conditions can influence in vitro regeneration responses. Lignified branches collected from 67 selected trees were cultivated ex vitro in culture pots at 25 °C to obtain epicormic shoots (explant sources). The explants were cultivated on an agar medium supplemented with 0.8 mg L-1 6-benzylaminopurine (BAP) for at least 21 months. In a second experiment, two different shoot multiplication conditions (temporary immersion-RITA® bioreactor and agar medium) and two culture medium formulations (Woody Plant Medium and modified Quoirin and Lepoivre medium) were tested. The results showed that the mean length of the epicormic shoots obtained in a pot culture was a function of donor age and was similar among the group of younger trees (ca. 20-200 years), and varied between older trees (ca. 300-800 years). The efficiency of in vitro shoot multiplication strictly depended on the genotype. A sustainable in vitro culture (defined as survival after 6 months) was only possible for half of the tested old donor trees, even when they survived the first month of in vitro growth. A continuous monthly increase in the number of in vitro cultured shoots was reported in younger oaks and in some old oaks. We found a significant effect of the culture system and the macro- and micronutrient composition on in vitro shoot growth. This is the first report demonstrating that the in vitro culture can be successfully applied to the propagation of even 800-year-old pedunculate oak trees.

9.
Biochim Biophys Acta Mol Cell Res ; 1870(7): 119501, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37276927

RESUMEN

Reactivating p53 and Inducing Tumor Apoptosis (RITA) has been reported to increase the p53 activity and to trigger p53-dependent apoptosis in cancer cells with wild-type p53. Tumor suppressor p53 interacts with nucleolar phosphoproteins nucleophosmin (NPM) and nucleolin (NCL), which have crucial role in many cellular processes. Specific NPM mutations associated with acute myeloid leukemia (AML) cause aberrant localization of NPM and p53 in the cytoplasm with possible impact on the p53 function. We tested an effect of RITA on primary cells, and we found significant RITA-induced changes in NPM and NCL phosphorylation associated with apoptosis in cells of AML patients, but not that of healthy donors. Subsequent screening of several AML cell lines revealed heterogeneous response to RITA, and confirmed an association of the specific phosphorylation with apoptosis. While decreased NCL phosphorylation at Threonines T76 and T84 could be attributed to RITA-induced cell cycle arrest, enhanced NPM phosphorylation at Threonine T199 was not accompanied by the cell cycle changes and it correlated with sensitivity to RITA. Simultaneously, inverse changes occurred at Serine S4 of the NPM. These new findings of RITA mechanism of action could establish the NPM pT199/pS4 ratio as a marker for suitability of RITA treatment of AML cells.


Asunto(s)
Leucemia Mieloide Aguda , Proteína p53 Supresora de Tumor , Humanos , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo , Apoptosis , Fosfoproteínas/genética , Fosfoproteínas/metabolismo , Leucemia Mieloide Aguda/metabolismo , Nucléolo Celular/metabolismo
10.
Aging Ment Health ; 27(12): 2446-2456, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36995263

RESUMEN

OBJECTIVES: Severe weather events have mental health consequences for survivors that may change over time. We assessed post-flood mental health longitudinally in three groups of mostly middle-aged and older adults who varied in current and prior severe weather experiences. METHOD: Predictors of central interest were age, perceived social support, state hope (including agency and pathways), recovery stressors, and prior lifetime trauma. Criterion variables included symptoms of depression, post-traumatic stress disorder (PTSD), and worry. RESULTS: Analyses of variance yielded significant Disaster Exposure Group x Wave interactions for depression and PTSD symptoms. Those with flooded homes and properties had elevated symptoms at Wave 1 which were reduced at Wave 2. Older age was associated with fewer symptoms of depression, PTSD, and worry. Recovery stressors and lifetime trauma predicted more PTSD symptoms. Greater agency predicted less PTSD and depression symptoms, whereas pathways predicted less worry. CONCLUSION: These data show that mental health symptoms may decrease over time for those directly impacted by severe flooding. State hope appears to contribute to better mental health after exposure to a devastating flood. Implications for understanding the dynamic relationships among risk variables and positive factors that promote post-disaster mental health in the years after a flood are considered.

11.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-986980

RESUMEN

OBJECTIVE@#To screen for small molecular compounds with selective inhibitory activity against cutaneous melanoma cells with BAP1 deletion.@*METHODS@#Cutaneous melanoma cells expressing wild-type BAP1 were selected to construct a BAP1 knockout cell model using CRISPR-Cas9 system, and small molecules with selective inhibitory activity against BAP1 knockout cells were screened from a compound library using MTT assay. Rescue experiment was carried out to determine whether the sensitivity of BAP1 knockout cells to the candidate compounds was directly related to BAP1 deletion. The effects of the candidate compounds on cell cycle and apoptosis were detected with flow cytometry, and the protein expressions in the cells were analyzed with Western blotting.@*RESULTS@#The p53 activator RITA from the compound library was shown to selectively inhibit the viability of BAP1 knockout cells. Overexpression of wild-type BAP1 reversed the sensitivity of BAP1 knockout cells to RITA, while overexpression of the mutant BAP1 (C91S) with inactivated ubiquitinase did not produce any rescue effect. Compared with the control cells expressing wild-type BAP1, BAP1 knockout cells were more sensitive to RITA-induced cell cycle arrest and apoptosis (P < 0.0001) and showed an increased expression of p53 protein, which was further increased by RITA treatment (P < 0.0001).@*CONCLUSION@#Loss of BAP1 results in the sensitivity of cutaneous melanoma cells to p53 activator RITA. In melanoma cells, the activity of ubiquitinase in BAP1 is directly related to their sensitivity to RITA. An increased expression of p53 protein induced by BAP1 knockout is probably a key reason for RITA sensitivity of melanoma cells, suggesting the potential of RITA as a targeted therapeutic agent for cutaneous melanoma carrying BAP1-inactivating mutations.


Asunto(s)
Humanos , Melanoma , Neoplasias Cutáneas , Proteína p53 Supresora de Tumor , Apoptosis , División Celular , Proteínas Supresoras de Tumor/genética , Ubiquitina Tiolesterasa/genética
12.
JTCVS Tech ; 13: 92-100, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36466372

RESUMEN

Objective: Robot-assisted coronary artery bypass (RCAB) is typically not offered to higher risk patients with reduced cardiopulmonary function, critical coronary artery disease, and challenging chest wall anatomy. In this study, we report the novel use of nonemergency intraoperative peripheral extracorporeal membrane oxygenation as partial cardiopulmonary support during RCAB for patients who were considered high-risk candidates for conventional CAB and at the same time not eligible for RCAB without cardiopulmonary support. Methods: Forty-five high risk patients (mean age, 68 years; Society of Thoracic Surgeons score, 6.27%; ejection fraction, 45%) underwent RCAB with nonemergency peripheral extracorporeal membrane oxygenation support for the following indications: inability to tolerate single-lung ventilation (n = 17; 38%), low ejection fraction <35% (n = 17; 38%), inadequate exposure of internal thoracic artery (n = 24; 53%), critical coronary artery disease (n = 16; 36%), and hemodynamic instability after anesthesia induction (n = 3; 7%). Following robotic internal thoracic artery takedown, all patients had beating heart minimally invasive direct CAB through a 2-inch minithoracotomy. Results: Up to 30 days, there were no strokes (0%), myocardial infarctions (0%), or access vessel complications (0%). One noncardiac related mortality (2.2%) was related to hemodialysis access issues in a patient with preexisting end-stage renal disease. One redo-CAB (2.2%) patient required sternotomy to locate the target vessel. Thirty-four (75.6%) patients were extubated within 6 hours of surgery. Conclusions: Our results examine the feasibility of using peripheral extracorporeal membrane oxygenation during RCAB for high-risk patients who otherwise had limited options. The use of peripheral extracorporeal membrane oxygenation in RCAB can potentially expand the surgical treatment options in high-risk coronary artery disease patients.

13.
JTCVS Tech ; 16: 76-88, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36510526

RESUMEN

Objective: Advanced hybrid coronary revascularization is the integration of sternal-sparing multivessel coronary artery bypass grafting and percutaneous coronary intervention in patients with multivessel coronary artery disease. We sought to review our advanced hybrid coronary revascularization experience over an 8.5-year period using robotic totally endoscopic coronary artery bypass with bilateral internal thoracic artery grafts and percutaneous coronary intervention. Methods: From August 2013 to February 2022, 664 patients underwent robotic totally endoscopic coronary artery bypass at our institution. Of the 293 patients who underwent totally endoscopic coronary artery bypass assigned to a hybrid revascularization strategy, 156 patients received bilateral internal thoracic artery grafts and are the subject of this review. Patients underwent percutaneous coronary intervention with drug-eluting stents before or after totally endoscopic coronary artery bypass. We reviewed early and midterm outcomes (up to 8 years) in this cohort of patients with intent-to-treat advanced hybrid coronary revascularization. Results: The mean age of patients was 65 ± 10 years. The mean Society of Thoracic Surgeons predicted risk of mortality was 1.26 ± 1.56. Triple-vessel disease occurred in 94% of patients, and 17% of patients had 70% or more left-main disease. The mean operative time was 311 ± 54 minutes, and the mean hospital length of stay was 2.7 ± 1.1 days. All patients had bilateral internal thoracic artery grafts; the total number of grafts was 334. Eight seven percentage of patients had totally endoscopic coronary artery bypass ×2, and 13% of patients had totally endoscopic coronary artery bypass ×3. One patient received totally endoscopic coronary artery bypass ×4. The mean number of grafts per patient was 2.14 ± 0.4, and the mean number of vessels stented was 1.23 ± 0.5. There were no conversions, perioperative stroke, or myocardial infarction. Early mortality occurred in 2 patients. Early graft patency was 98% (209/214 grafts); left internal thoracic artery to left anterior descending patency was 100% (66/66 grafts). At 8-year follow-up in 155 patients (mean 39 ± 26 months), all-cause and cardiac-related mortality were 11.6% and 3.9%, respectively. Freedom from major adverse cardiac/cerebrovascular events including repeat revascularization was 94%. Conclusions: In patients with multivessel coronary artery disease, integrating robotic totally endoscopic coronary artery bypass with bilateral internal thoracic artery and percutaneous coronary intervention resulted in excellent early and midterm outcomes. Further studies are warranted.

14.
Front Immunol ; 13: 857905, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36177052

RESUMEN

Background: To assess whether HIV self-testing (HIVST) has a better performance in identifying HIV-infected cases than the facility-based HIV testing (HIVFBT) approach. Methods: A cross-sectional study was conducted among men who have sex with men (MSM) by using an online questionnaire (including information on sociodemographic, sexual biography, and HIV testing history) and blood samples (for limiting antigen avidity enzyme immunoassay, gene subtype testing, and taking confirmed HIV test). MSM who were firstly identified as HIV positive through HIVST and HIVFBT were compared. Chi-square or Fisher's exact test was used to explore any association between both groups and their subgroups. Results: In total, 124 MSM HIV cases were identified from 2017 to 2021 in Zhuhai, China, including 60 identified through HIVST and 64 through HIVFBT. Participants in the HIVST group were younger (≤30 years, 76.7% vs. 46.9%), were better educated (>high school, 61.7% vs. 39.1%), and had higher viral load (≥1,000 copies/ml, 71.7% vs. 50.0%) than MSM cases identified through HIVFBT. The proportion of early HIV infection in the HIVST group was higher than in the HIVFBT group, identified using four recent infection testing algorithms (RITAs) (RITA 1, 46.7% vs. 25.0%; RITA 2, 43.3% vs. 20.3%; RITA 3, 30.0% vs. 14.1%; RITA 4, 26.7% vs. 10.9%; all p < 0.05). Conclusions: The study showed that HIVST has better HIV early detection among MSM and that recent HIV infection cases mainly occur in younger and better-educated MSM. Compared with HIVFBT, HIVST is more accessible to the most at-risk population on time and tends to identify the case early. Further implementation studies are needed to fill the knowledge gap on this medical service model among MSM and other target populations.


Asunto(s)
Infecciones por VIH , Minorías Sexuales y de Género , Estudios Transversales , Infecciones por VIH/diagnóstico , Infecciones por VIH/epidemiología , Prueba de VIH , Homosexualidad Masculina , Humanos , Masculino , Autocuidado , Autoevaluación
15.
JTCVS Tech ; 14: 107-113, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35967226

RESUMEN

Objective: This study aimed to examine the feasibility and safety of minimally invasive cardiac surgery coronary artery bypass grafting using an ultrasonically skeletonized internal thoracic artery in the authors' initial experience. Methods: From February 2012 to May 2021, 247 consecutive patients who underwent minimally invasive coronary artery bypass grafting using an ultrasonically skeletonized internal thoracic artery were reviewed retrospectively. Internal thoracic arteries were harvested in a full skeletonized fashion using an ultrasonic scalpel via left minithoracotomy. Bilateral internal thoracic arteries were used in 108 patients, and the internal thoracic arteries as in situ grafts were used in 393 anastomoses. Total arterial revascularization was performed in 126 patients, and 142 patients underwent aortic nontouch minimally invasive coronary artery bypass grafting. Results: The patients' mean (range) age was 65.9 ± 11.5 (30-90) years. The mean (range) number of anastomoses performed was 2.6 ± 1.1 (1-6). Forty-six patients (18.6%) had 4 grafts, 94 patients (38.1%) had 3 grafts, and 60 patients (24.3%) had 2 grafts. Minimally invasive coronary artery bypass grafting was completed without conversion to sternotomy in all patients. Cardiopulmonary bypass was performed in 3 patients (1.2%), reinterventions due to bleeding were performed in 7 patients (2.8%), and chest wound infections were observed in 5 patients (2.0%). There was 1 (0.4%) mortality. Conclusions: Minimally invasive coronary artery bypass grafting using an ultrasonically skeletonized internal thoracic artery is feasible and has shown good perioperative outcomes. This approach has the potential for further optimization with revascularization strategies.

16.
J Environ Manage ; 321: 115722, 2022 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-35988404

RESUMEN

Factors driving community recovery trajectories after disaster are not well understood. We assess why some communities show stronger recoveries from disaster than others, examining the role of four policy toolkits that U.S. county governments frequently adopt to recover from disaster. Using mixed methods, we examine the cases of Hurricanes Katrina and Rita with a novel dataset of recovery policies adopted within each Louisiana parish following the disasters. We typologize recovery strategies and analyze policy adoption patterns after crises. To compare which policy toolkit leads to the best recovery outcomes, we use synthetic control experiments on the 20 parishes hit by Hurricanes Katrina and Rita between August and September 2005, tracking net income inflow and net in-migration measures from 1997 to 2018 over 1408 parish-year observations, paired with qualitative case studies of parish policies and recovery outcomes. On average, soft and local recovery policies focused on community policies and feedback helped parishes stem the flow of finances away from the disaster-zone, as did infrastructural 'hard' policies, to a degree. in comparison, state policies focused on top-down planning experienced weaker recovery. Evidence shows that soft and local policy toolkits can accelerate recovery and that governments seeking to rebuild infrastructure should invest in locally-engaged community development in order to attain better overall recovery.


Asunto(s)
Tormentas Ciclónicas , Planificación en Desastres , Desastres , Louisiana , Políticas
17.
Front Plant Sci ; 13: 895971, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35812929

RESUMEN

The aim of this study was to propagate axillary shoots of Cannabis sativa L. using liquid medium in temporary immersion bioreactors. The effect of immersion frequency (3 or 6 immersions per day), explant type (apical or basal sections), explant number (8, 10, and 16 explants), mineral medium (Murashige and Skoog half-strength nitrates, ß-A and ß-H, all supplemented with 2-µM metatopoline), sucrose supplementation (2, 0.5, and 0% sucrose), culture duration (4 and 6 weeks), and bioreactor type (RITA® and Plantform™) were investigated. As a result, we propose a protocol for the proliferation of cannabis apical segments in RITA® or Plantform™ bioreactors. The explants (8 per RITA® and 24 per Plantform™) are immersed for 1 min, 3 times per day in ß-A medium supplemented with 2-µM metatopoline and 0.5% of sucrose and subcultured every 4 weeks. This is the first study using temporary immersion systems in C. sativa production, and our results provide new opportunities for the mass propagation of this species.

18.
Cancer Sci ; 113(9): 3071-3084, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35701858

RESUMEN

Bladder cancer (BC) is one of the most prevalent malignancies worldwide, but it lacks effective targeted therapy due to its elusive molecular mechanism. Therefore, it is important to further investigate the molecular mechanisms that mediate BC progression. By performing a tumor tissue-based gene microarray and shRNA library screening, we found that recombination signal binding protein for immunoglobulin kappa J region (RBPJ) interacting and tubulin associated 1 (RITA1) is crucial for the growth of BC cells. Moreover, RITA1 is aberrantly highly expressed in BC tissues and is also correlated with poor prognosis in patients with BC. Mechanistically, we determined that RITA1 recruits tripartite motif containing 25 (TRIM25) to ubiquitinate RBPJ to accelerate its degradation via proteasome, which leads to the transcriptional inhibition of Notch1 downstream targets. Our results suggest that aberrant high expression of RITA1 drives the growth of BC cells via the RITA1/TRIM25/RBPJ axis and RITA1 may serve as a promising therapeutic target for BC.


Asunto(s)
Neoplasias de la Vejiga Urinaria , Línea Celular Tumoral , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , Humanos , Proteína de Unión a la Señal Recombinante J de las Inmunoglobulinas/genética , ARN Interferente Pequeño/genética , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Proteínas de Motivos Tripartitos/genética , Proteínas de Motivos Tripartitos/metabolismo , Ubiquitina-Proteína Ligasas/genética , Ubiquitina-Proteína Ligasas/metabolismo , Neoplasias de la Vejiga Urinaria/genética
19.
Cancer Epidemiol ; 79: 102200, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35772301

RESUMEN

BACKGROUND: Cancer is an important risk factor in patients with COVID-19. We aimed to describe the clinical and demographic characteristics associated with mortality in patients with cancer who were infected with SARS-CoV-2. METHODS: We conducted a retrospective longitudinal study of 1206 patients with confirmed SARS-CoV-2 infection and cancer, registered in the Argentinean Network of Hospital-Based Cancer Registries (RITA) from March 31, 2020 to January 31, 2021. Demographic and clinical differences between survivors and non-survivors were summarized using descriptive statistics. The primary endpoint was all-cause mortality within 30 days of COVID-19 diagnosis. Risk factors for mortality were identified using logistic regression models. RESULTS: 1206 patients with cancer and confirmed SARS-CoV-2 infection were included, median age was 54 years (interquartile range: 42-65); 793 (65.8%) were female. 1101 (91.3%) had solid tumors and 105(8.7%) had hematological malignancies. The most frequent solid tumor was breast (278, 23.1%), while lymphoma was the main hematological one (59, 4.9%). Cervical cancer was more frequent in survivors, while lung cancer predominated in non-survivors. 275 (22.8%) patients were diagnosed with cancer within the past year. A total of 129 (10.7%) patients died within 30 days after COVID-19 diagnosis, with a case fatality rate of 15.2% (16/105) for hematologic malignancies and 10.3% (113/1101) for solid tumors. Multivariable regression analysis showed that age 60-79 (odds ratio [OR]: 4.69, 95% confidence interval [CI]: 2.72-9.70), age ≥ 80 (OR: 12.86, 95%CI: 5.08-32.54), time since cancer diagnosis < 1 year (OR: 2.49, 95%CI: 1.57-3.93) and 1-2 years (OR: 2.20, 95%CI: 1.36-3.57), and lung cancer (OR: 4.35, 95%CI: 2.02-9.36) were risk factors for death. CONCLUSION: Patients with cancer and SARS-CoV-2 infection had a high case-fatality rate. Identified risk factors (older age, recent diagnosis and lung type) could guide prevention strategies aimed at reducing the risk of dying from COVID-19 in cancer patients.


Asunto(s)
COVID-19 , Neoplasias Hematológicas , Neoplasias Pulmonares , Anciano , COVID-19/epidemiología , Prueba de COVID-19 , Femenino , Hospitales , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Sistema de Registros , Estudios Retrospectivos , SARS-CoV-2
20.
Anticancer Res ; 42(6): 2931-2937, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35641264

RESUMEN

BACKGROUND/AIM: Oral squamous cell carcinoma (OSCC) is one of the most common tumors of the head and neck region. The tumor suppressor gene p53 (TP53) is the most frequently mutated gene in OSCC and TP53 mutations are associated with decreased survival and resistance to chemotherapy in patients with OSCC. Therefore, therapeutic strategies targeting TP53 reactivation are required to effectively treat OSCC. In this study, we investigated the effect of various p53-reactivating small molecules (RITA, PRIMA-1, and CP-31398) on the proliferation of human OSCC cell lines (Ca9-22, HSC-2, HSC-3, and HSC-4) derived from human oral tissues bearing a mutant TP53 gene. MATERIALS AND METHODS: Apoptosis induction by RITA was assessed by measuring Annexin V and propidium iodide (PI)-positive cells using flow cytometry. p53 and murine double minute 2 (MDM2) phosphorylation and Bax expression were detected in the lysates of RITA-treated Ca9-22 cells using western blotting. RESULTS: RITA markedly inhibited the growth of Ca9-22, HSC-2, HSC-3, and HSC-4 cells. In Ca9-22 cells, RITA induced apoptosis and inhibited cell proliferation while increasing p53 phosphorylation and Bax expression; however, RITA did not induce MDM2 phosphorylation. CONCLUSION: The inhibitory effect of RITA on human OSCC cell proliferation is mediated by apoptosis induction through p53 and Bax.


Asunto(s)
Neoplasias de la Boca , Carcinoma de Células Escamosas de Cabeza y Cuello , Proteína p53 Supresora de Tumor , Apoptosis , Genes p53 , Humanos , Neoplasias de la Boca/tratamiento farmacológico , Neoplasias de la Boca/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológico , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Proteína p53 Supresora de Tumor/metabolismo , Proteína X Asociada a bcl-2/metabolismo
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