Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 37
Filtrar
1.
Glob Health Sci Pract ; 12(Suppl 2)2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38575360

RESUMEN

INTRODUCTION: Young newly married women and first-time parents (FTPs), particularly those living in slum settlements, have a high unmet need for modern contraceptive methods to limit and space births. We describe an intervention in which adolescents and youth sexual and reproductive health (AYSRH) services tailored to FTPs were incorporated into the government's existing family planning (FP) program in 5 cities of Uttar Pradesh. We examined the effect of this intervention on modern contraceptive use among FTPs aged 15-24 years. METHODS: To assess the effect of this pilot, in 2019, 1 year after the implementation of the program, we analyzed community-based output tracking survey data on 549 married women who are FTPs in the pilot cities. These FTPs were compared with 253 women who were FTPs from other cities where the program was implemented without a specific focus on FTPs. Descriptive statistics and multivariate logistic regression analysis were applied to understand the association between exposure to FP information, either through accredited social health activists or through service delivery points, and use of modern contraceptives. RESULTS: Use of modern contraceptives was higher among FTPs in the 5 pilot cities than non-pilot cities (39% vs. 32%; P<.05). The interaction effect of city type and exposure to the information showed a positive association between modern contraceptive use and program exposure, greater in pilot cities than non-pilot cities. CONCLUSIONS: Higher uptake of modern contraceptives among young women may be achieved when an FTP-focused intervention is layered on the government's existing FP programs. Future studies with a longer duration of implementation, in a wider geography, and with longitudinal design are recommended to provide more robust measures of high impact intervention/practices in urban areas.


Asunto(s)
Agentes Comunitarios de Salud , Conducta Anticonceptiva , Anticoncepción , Servicios de Planificación Familiar , Humanos , Femenino , Adolescente , India , Adulto Joven , Conducta Anticonceptiva/estadística & datos numéricos , Padres , Ciudades , Proyectos Piloto , Adulto
2.
Sci Rep ; 14(1): 9712, 2024 Apr 27.
Artículo en Inglés | MEDLINE | ID: mdl-38678146

RESUMEN

Hydromagnetically associated heat convection can greatly enhance the performance of high-efficiency thermal appliances and renewable energy sources through an optimized design. This investigation examines the production of thermodynamic irreversibility and heat convection for a double lid-driven flow within a partially porous stratified hexagonal enclosure. The top and bottom-wall are moving in the opposite direction with an equal velocity U0. The top-wall and the bottom-wall are kept at temperature Tc and Th (Th  >  Tc) while the slanted walls are assumed to be thermally insulated. A constant magnetic field is employed in the horizontal x-direction. The hexagonal cavity was filled with a micropolar hybrid nanofluid Ag-MgO/water. The system of dimensionless equations was solved by the finite difference method (FDM) associated with successive over-relaxation (SOR), successive under-relaxation (SUR), and Gauss-Seidel iteration tactics and required results are computed with problem specific program in MATLAB code. The results indicate that the Ra and the thickness of the porous layer (Xp) significantly influences heat convection and thermal irreversibility processes. The Nuavg and STotal rises 6.299% and 3.373% as ' ϕ hnf ' enhances from 0 to 4%, respectively. Furthermore, as the values of Ra, Ha, K0, and ϕ hnf increase, Beavg experiences a decline of 53.73%, 11.04%, 38.36%, and 0.09% respectively. Also, movement of wall has a significant impact on heat transfer rates and entropy production. The present study may be extended in numerous areas to mimic the problems like-(1) onset of thermo-mechanical process for solid-fluid interaction in a conduit. (2) Thermos-chemical process with extraction of ions in two-phase fluid for double layer plating on a continuously moving sheet, as region of porous stratum saturated with a class of fluid and region without porous medium occupied with other fluid.

3.
Indian J Plast Surg ; 56(4): 367-372, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37705817

RESUMEN

Background : Facial dog bite injuries result in significant emotional, psychological, and physical trauma to the victims involved and should be considered a significant health issue. The purpose of this study is to share our experience in the management and to add to the existing medical literature regarding the epidemiological patterns of facial dog bite injuries. Materials and Methods : This is a single-center retrospective observational study conducted at Dr. RML Hospital, New Delhi, from January 2021 to January 2022. A total of 105 patients were included. The wounds were managed according to the recommendations made by the national rabies control program and surgical intervention was performed in the form of primary suturing or flap cover. Results : Children of age group 0 to 10 years are most commonly affected. Pet dogs are the cause in 61% of cases and 57.1% of bites were provoked. Midface is most commonly affected and modified Lackmann's class 3A and 3B are the most common wounds. Conclusion : In view of raising incidence of dog bites with pet dogs, the general public needs to be educated regarding the practices to prevent these injuries. Postexposure prophylaxis should be given to all affected individuals irrespective of the vaccination status of the dog. Immediate surgical intervention gives better results.

4.
Environ Monit Assess ; 195(9): 1046, 2023 Aug 17.
Artículo en Inglés | MEDLINE | ID: mdl-37589797

RESUMEN

Gypsum-enriched aquifers (GEA) and intensive agriculture regions (IAR) in semi-arid regions are responsible for very high amounts of sulfate and nitrate in many groundwater systems of the world, respectively. However, in such regions, the problem of nitrate pollution and its associated health risk has been increasing and emerging as a global issue. However, along with nitrate, sulfate contamination and its potential health risks are often neglected worldwide in these regions. Therefore, considering sulfate along with nitrate as a significant threat to water quality in such regions, this study aimed to characterize hydrochemistry, factors controlling groundwater quality, and assessment of risk to human health. To accomplish this objective, 116 groundwater samples were collected over pre-monsoon (PRM) and post-monsoon (POM) (2019) seasons in Bemetara district. As per Bureau of Indian standards (BIS) for drinking, SO42- (28 and 19%) and NO3- (7 and 35%) exceeded the permissible limits in PRM and POM seasons, respectively; thereby, groundwater was not suitable for drinking. SO42- and NO3- pollution sources were identified and mainly attributed to gypsum dissolution and agricultural activities as well as domestic sewage discharge, respectively. In addition, SO42-and NO3- risk assessment results show that total 20% to 46% of all samples surpassed the permissible limit (HQ = 1) of risk to children and adults, over both seasons. To ensure drinking water security in this region, sustainable management of agricultural activities and treatment should be done to reduce the potential health risks due to SO42- and NO3-.


Asunto(s)
Agua Subterránea , Nitratos , Adulto , Niño , Humanos , Sulfatos , Sulfato de Calcio , Monitoreo del Ambiente , India , Calidad del Agua
5.
Indian J Otolaryngol Head Neck Surg ; 75(2): 1035-1039, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37275069

RESUMEN

Background: Jacob's disease is a rare pathology characterized by elongation/ enlargement of coronoid process of mandible with formation of pseudoarticulation with zygomatic arch. It presents clinically as restricted mouth opening and is often misdiagnosed as temporomandibular joint pathology. Case Presentation: We performed cross sectional imaging and evaluation of Jacob's disease in a 14-year-old girl with restricted mouth opening, CT images including Multiplanar Reconstruction and Volume Rendered Technique revealed enlarged left coronoid process of mandible while open mouth CT images and MR images concluded the presence of joint between enlarged coronoid process and zygomatic arch. Conclusions: Coronoid process hypertrophy and Jacob's disease are important differentials which should be considered in evaluation of restricted mouth opening. We propose that apart from CT, MR imaging should be considered in such cases for better pre-operative evaluation of joint formation. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-022-03323-7.

6.
Environ Sci Pollut Res Int ; 30(28): 71813-71825, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-34622409

RESUMEN

The leachates emanating from the landfills are high in organic loads and thus become potential sources of contamination for both surface and groundwater. As the landfill ages, the nature of leachate changes from acidic to alkaline. The change in pH level affects the chemical oxygen demand (COD)/biochemical oxygen demand (BOD) ratio and when it is less than 0.63, chemical treatments are more effective over the biological treatment methods such as upflow anaerobic sludge blankets (UASB). The existing literature suggests coagulation-flocculation and advanced oxidation process (Fenton) as effective methods for treating wastewater but no comparison of the two are available. Thus, the present study attempts to identify the most efficient coagulants out of ferric chloride (FeCl3), ferrous sulphate (FeSO4) and alum [Al2(SO4)3]. Ferric chloride leading to 99% colour removal, 98% COD removal, 99% decrease in total organic carbon, 94.3% removal in NH3-N and 91.4% removal in total Kjeldahl nitrogen is observed to be the most efficient coagulant and surprisingly, proves to be even better than Fenton. To understand the field applicability of the two treatment procedures, coagulation with FeCl3 and Fenton are compared with the UASB method which is currently employed at Gazipur landfill site, Delhi. With lesser operational cost than UASB, both FeCl3 and Fenton perform better on cost-efficiency scale. Switching from in-suit UASB method to the FeCl3 method of treatment may result in decreasing the operational cost by 71.9% and to conventional Fenton may result in decreasing the operational cost by 76.8%.


Asunto(s)
Eliminación de Residuos Líquidos , Contaminantes Químicos del Agua , Eliminación de Residuos Líquidos/métodos , Contaminantes Químicos del Agua/análisis , Compuestos Férricos , Instalaciones de Eliminación de Residuos
7.
Comput Electr Eng ; 101: 108028, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35498557

RESUMEN

The concept of fuzzy set, intuitionistic set, and mediative fuzzy set as a generalization of a crisp set have been introduced in many real-life applications. The concept of crisp relation between elements of sets can be extended to fuzzy relations. Extended relations will be considered as relations on fuzzy sets. In this work, we developed the concept of mediative fuzzy relation and meditative fuzzy projection in the context of fuzzy relation and fuzzy projection. We extended the basic operations of fuzzy projection into intuitionistic fuzzy projection and then in the mediative fuzzy projection. We have shown the credibility and impact of mediative index factor involves in the mediative fuzzy projection in context of prediction work in relation to the proposed model. Further, we applied the mediative fuzzy projection in the medical diagnosis in post-COVID-19 patients. The obtained results have also been discussed with their geometrical representation.

8.
Cureus ; 14(4): e23847, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35402111

RESUMEN

BACKGROUND:  Failed mechanical thrombectomy due to a refractory emergent large vessel occlusion (RELVO) in patients presenting with an acute stroke poses a major challenge to the outcomes. OBJECTIVE:  We demonstrate the use of coronary stents in the intracranial circulation as rescue stenting for an already expensive mechanical thrombectomy procedure in a mid-low socioeconomic setting. METHODS:  A retrospective, multicenter study was conducted between December 2015 and January 2021. The studied cohort were patients who required the use of a rescue stenting using a coronary stent for emergent large vessel occlusion to avoid failed recanalization. Failed recanalization was defined as failed vessel recanalization after at least two passes. Patient demographic data, procedure specifics, type of stent used, and procedural outcomes were collected. RESULTS:  A total of 26 patients with acute ischemic stroke were included from eight different centers across India. Out of 26 patients, 19 (73.0%) were male and seven were female (26.9%). The mean age was 53.6 years, the youngest patient was 23 years old and the eldest was 68 years old. Seven patients (26.9%) had posterior circulation stroke due to occlusion of the vertebral or basilar artery and 19 patients (73.0%) had anterior circulation stroke median NIHSS at presentation was 16 (range 10 to 28) in anterior circulation stroke and 24 (range 16 to 30) in posterior circulation stroke. Intravenous thrombolysis with tissue plasminogen activator (IV tPA) was given in three patients (11.5%). The hospital course of two patients was complicated by symptomatic intracranial hemorrhage (sICH), which was fatal. Favorable revascularization outcome and favorable functional outcome was achieved in 22 patients (84.6%), three patients passed away (11.5%), and one patient was lost to follow up. CONCLUSIONS:  Overall, our study finds that rescue stenting using coronary stents can potentially improve outcomes in refractory large vessel occlusions while minimizing costs in low-mid economic settings.

9.
Glob Health Sci Pract ; 10(1)2022 02 28.
Artículo en Inglés | MEDLINE | ID: mdl-35294391

RESUMEN

INTRODUCTION: The Most Significant Change (MSC) technique is a complex-aware monitoring and evaluation tool, widely recognized for various adaptive management purposes. The documentation of practical examples using the MSC technique for an ongoing monitoring purpose is limited. We aim to fill the current gap by documenting and sharing the experience and lessons learned of The Challenge Initiative (TCI), which is scaling up evidence-based family planning (FP) and adolescent and youth sexual and reproductive health (AYSRH) interventions in 11 countries in Asia and sub-Saharan Africa. METHODS: The qualitative assessment took place in early 2021 to document TCI's use and adaptation of MSC and determine its added value in adaptive management, routine monitoring, and cross-learning efforts. Focus group discussions and key informant interviews were conducted virtually with staff members involved in collecting and selecting MSC stories. RESULTS: TCI has had a positive experience with using MSC to facilitate adaptive management in multiple countries. The use of MSC has created learning opportunities that have helped diffuse evidence-based FP and AYSRH interventions both within and across countries. The responsive feedback step in the MSC process was viewed as indispensable to learning and collaboration. There are several necessary inputs to successful use of the method, including buy-in about the benefits, training on good interviewing techniques and qualitative research, and dedicated staff to manage the process. CONCLUSION: Our assessment results suggest that the MSC technique is an effective qualitative data collection tool to strengthen routine monitoring and adaptive management efforts that allows for flexibility in how project stakeholders implement the process. The MSC technique could be an important tool for global health practitioners, policy makers, and researchers working on complex interventions because they continually need to understand stakeholders' needs and priorities, learn from lessons and evidence-based practices, and be agile about addressing potential challenges.


Asunto(s)
Servicios de Planificación Familiar , Salud Sexual , Personal Administrativo , Adolescente , Salud Global , Humanos , Investigación Cualitativa
10.
Bioinformation ; 18(8): 724-729, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-37323560

RESUMEN

Oral cancer is becoming more common, and it threatens to be a serious worldwide medical issue. Hence, it is of interest to elucidate the networks between proteins and biologically active compounds, as well as their functional annotations, and cell signaling pathways. The online STRING software was used to create a molecular genetics interaction network named AZURIN on oral bacterial proteins. We also used the cystoscope software to identify 11 nodes and 16 edges with an average node order of 2.91. Thus, we document data on the interaction of protein networks with other proteins for identifying potential therapeutic drug candidates linked to oral disease.

11.
Bioinformation ; 18(9): 757-763, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-37426511

RESUMEN

Data on the microbial composition among tobacco chewers and oral cancer patients in Rajasthan, India is of interest. NGS analysis from tobacco chewers and oral cancer comprised the most abundant and core microbial taxa in the oral cavity. It shows that highly pathogenic phylum consisting of 6% Fusobacteria and 9% Firmicutes are observed in oral cancer samples; whereas, 0.6% Treponema, 34% Firmicutes, 0.02% Mollicutes, and 4% Fusobacteria are seen in tobacco chewers. Thus, data shows that the most abundant and core microbial taxa are found in the oral cavity of tobacco chewers and oral cancer patients in Rajasthan, India.

12.
Indian J Plast Surg ; 54(3): 308-313, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34667516

RESUMEN

Background Burn is a leading cause of fatality in a developing country. C-reactive protein levels (CRP) and procalcitonin (PCT) can be prognostic indicators for the burn patients' mortality. Aim To assess serial levels of serum PCT and serum CRP as prognostic indicators in burns. Patient and Methods In patients admitted with burns, alternate-day serum PCT and CRP were measured from the time of admission until the time of discharge or until survival. The change in trends of CRP and PCT serum levels were studied, and it was then correlated with mortality among these burn patients. Results The first-day value of serum PCT > 1772 pg/mL and serum CRP > 71 mg/mL or any value of serum PCT > 2163 pg/mL and of serum CRP > 90 mg/L indicate a poor prognosis in burns. Conclusions The day-1 values of PCT and CRP were significantly higher in nonsurvivors than survivors in burns. The increasing trends of serum PCT and CRP levels are independent predictors of mortality in burns requiring prompt intervention. Rising PCT and CRP level denote poor prognosis in burns with an increased likelihood of death by 4.5 and 23.6 times, respectively.

13.
Indian J Plast Surg ; 54(2): 221-224, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-34239250

RESUMEN

A congenital nevi is a pigmented patch which requires complete surgical excision for cosmetic reasons. Here, we report a case of a patient with facial hairy pigmented lesion, occupying the right half of her face since birth, who underwent complete surgical excision and staged reconstruction utilizing, preexpanded forehead and neck skin. We used two rectangular tissue expanders with 150 and 300 cubic cm of volumes inserted in the forehead and the neck, respectively. The length of the expanders selected were equal to 1.2 to 1.5 times the length of their respective lesions, whereas the width of the base of the expanders were approximately similar to the width of their defects. It is concluded with this case report that tissue expansion provides a good cosmetic and anatomical correction to cover large defects, with adjacent skin having similar properties.

14.
J Radiat Res ; 62(3): 380-389, 2021 May 12.
Artículo en Inglés | MEDLINE | ID: mdl-33842963

RESUMEN

Non-homologous end joining is one of the main pathways for DNA double-strand break (DSB) repair and is also implicated in V(D)J recombination in immune system. Therefore, mutations in non-homologous end-joining (NHEJ) proteins were found to be associated with immunodeficiency in human as well as in model animals. Several human patients with mutations in XRCC4 were reported to exhibit microcephaly and growth defects, but unexpectedly showed normal immune function. Here, to evaluate the functionality of these disease-associated mutations of XRCC4 in terms of radiosensitivity, we generated stable transfectants expressing these mutants in XRCC4-deficient murine M10 cells and measured their radiosensitivity by colony formation assay. V83_S105del, R225X and D254Mfs*68 were expressed at a similar level to wild-type XRCC4, while W43R, R161Q and R275X were expressed at even higher level than wild-type XRCC4. The expression levels of DNA ligase IV in the transfectants with these mutants were comparable to that in the wild-type XRCC4 transfectant. The V83S_S105del transfectant and, to a lesser extent, D254Mfs*68 transfectant, showed substantially increased radiosensitivity compared to the wild-type XRCC4 transfectant. The W43R, R161Q, R225X and R275X transfectants showed a slight but statistically significant increase in radiosensitivity compared to the wild-type XRCC4 transfectant. When expressed as fusion proteins with Green fluorescent protein (GFP), R225X, R275X and D254Mfs*68 localized to the cytoplasm, whereas other mutants localized to the nucleus. These results collectively indicated that the defects of XRCC4 in patients might be mainly due to insufficiency in protein quantity and impaired functionality, underscoring the importance of XRCC4's DSB repair function in normal development.


Asunto(s)
Proteínas de Unión al ADN/genética , Microcefalia/genética , Mutación/genética , Tolerancia a Radiación/genética , Línea Celular Tumoral , Núcleo Celular/metabolismo , Regulación Neoplásica de la Expresión Génica , Humanos , Transporte de Proteínas , Fracciones Subcelulares/metabolismo
15.
Mol Breed ; 41(7): 46, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37309385

RESUMEN

A genome-wide association study (GWAS) for 10 yield and yield component traits was conducted using an association panel comprising 225 diverse spring wheat genotypes. The panel was genotyped using 10,904 SNPs and evaluated for three years (2016-2019), which constituted three environments (E1, E2 and E3). Heritability for different traits ranged from 29.21 to 97.69%. Marker-trait associations (MTAs) were identified for each trait using data from each environment separately and also using BLUP values. Four different models were used, which included three single trait models (CMLM, FarmCPU, SUPER) and one multi-trait model (mvLMM). Hundreds of MTAs were obtained using each model, but after Bonferroni correction, only 6 MTAs for 3 traits were available using CMLM, and 21 MTAs for 4 traits were available using FarmCPU; none of the 525 MTAs obtained using SUPER could qualify after Bonferroni correction. Using BLUP, 20 MTAs were available, five of which also figured among MTAs identified for individual environments. Using mvLMM model, after Bonferroni correction, 38 multi-trait MTAs, for 15 different trait combinations were available. Epistatic interactions involving 28 pairs of MTAs were also available for seven of the 10 traits; no epistatic interactions were available for GNPS, PH, and BYPP. As many as 164 putative candidate genes (CGs) were identified using all the 50 MTAs (CMLM, 3; FarmCPU, 9; mvLMM, 6, epistasis, 21 and BLUP, 11 MTAs), which ranged from 20 (CMLM) to 66 (epistasis) CGs. In-silico expression analysis of CGs was also conducted in different tissues at different developmental stages. The information generated through the present study proved useful for developing a better understanding of the genetics of each of the 10 traits; the study also provided novel markers for marker-assisted selection (MAS) to be utilized for the development of wheat cultivars with improved agronomic traits. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-021-01240-1.

18.
JPRAS Open ; 21: 75-85, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32158889

RESUMEN

BACKGROUND: The estimated incidence of spina bifida is 1-2 cases per 1000 population. In earlier literature, the global prevalence of meningomyelocele (MMC) is reported as 0.8-1.0 per 1000 live births. This retrospective study analyses the outcome of various surgical procedures performed for the closure of MMC defects. METHOD: A total of 22 patients with MMC defects who underwent repair at our institute from July 2016 to August 2018 were included in the study. A retrospective review of all the cases operated was completed to analyse patient demography including defect size, defect location, surgical procedures, complications and the final outcome. RESULTS: Out of 22 cases, wherein the neurosurgery department sought help from the plastic surgery department, 11 defects were closed using the Limberg flap technique, 4 defects were closed with either primary closure or the double flap rotation flaps, one defect was closed using the triple rotation flap and 2 defects were closed using the local transposition flap cover technique. Complications were noted in only three cases. One patient had a local wound infection, while in two other cases, wound dehiscence was observed. All 3 cases were managed conservatively. On average, it takes approximately 70 days in India to close such defects. CONCLUSION: MMC defects can be effectively managed with local flap options such as Limberg flap, local transposition flap or rotation flaps. Various reasons for the delay in closure were reported in patients late to our centre, when the first point of contact was with other departments.

19.
J Radiat Res ; 59(6): 700-708, 2018 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-30247612

RESUMEN

XRCC4 is one of the core factors for DNA double-strand break (DSB) repair through non-homologous end joining (NHEJ). XRCC4 is phosphorylated by DNA-dependent protein kinase (DNA-PK), with Ser260 and Ser320 (Ser318 in the alternatively spliced form) being the major phosphorylation sites in vitro. It was recently reported that Ser320 is phosphorylated by DNA-PK in response to DNA damage; however, it is currently unclear whether Ser260 is phosphorylated in cellulo in response to DNA damage. Herein, we generated an antibody against XRCC4 phosphorylated on Ser260 and examined its phosphorylation status via Western blotting. XRCC4 Ser260 phosphorylation increased after irradiation with 30-300 Gy of γ-rays and was suppressed by DNA-PK inhibitor but not by ATM inhibitor. Moreover, XRCC4 Ser260 phosphorylation decreased in DNA-PKcs-deficient cells. These observations indicate that XRCC4 Ser260 is phosphorylated by DNA-PK in cellulo. The XRCC4S260A mutant reversed the high radiosensitivity of XRCC4-deficient M10 cells to a similar level to that of wild-type XRCC4. However, the clonogenic survival of cells expressing the XRCC4S260A mutant was slightly but significantly lower than that of those expressing wild-type XRCC4. In addition, XRCC4S260A-expressing cells displayed a significantly greater number of γ-H2AX foci than XRCC4WT-expressing cells 4 h after 1 Gy irradiation and without irradiation. The present results suggest a potential role of XRCC4 Ser260 phosphorylation by DNA-PK in DSB repair.


Asunto(s)
Roturas del ADN de Doble Cadena , Proteína Quinasa Activada por ADN/metabolismo , Proteínas de Unión al ADN/metabolismo , Fosfoserina/metabolismo , Línea Celular Tumoral , Reparación del ADN/genética , Rayos gamma , Humanos , Mutación/genética , Fosforilación
20.
Exp Cell Res ; 362(2): 450-460, 2018 01 15.
Artículo en Inglés | MEDLINE | ID: mdl-29233683

RESUMEN

X-ray repair cross-complementing group 4 (XRCC4), a repair protein for DNA double-strand breaks, is cleaved by caspases during apoptosis. In this study, we examined the role of XRCC4 in apoptosis. Cell lines, derived from XRCC4-deficient M10 mouse lymphoma cells and stably expressing wild-type XRCC4 or caspase-resistant XRCC4, were established and treated with staurosporine (STS) to induce apoptosis. In STS-induced apoptosis, expression of wild-type, but not caspase-resistant, XRCC4 in XRCC4-deficient cells enhanced oligonucleosomal DNA fragmentation and the appearance of TUNEL-positive cells by promoting nuclear translocation of caspase-activated DNase (CAD), a major nuclease for oligonucleosomal DNA fragmentation. CAD activity is reportedly regulated by the ratio of two inhibitor of CAD (ICAD) splice variants, ICAD-L and ICAD-S mRNA, which, respectively, produce proteins with and without the ability to transport CAD into the nucleus. The XRCC4-dependent promotion of nuclear import of CAD in STS-treated cells was associated with reduction of ICAD-S mRNA and protein, and enhancement of phosphorylation and nuclear import of serine/arginine-rich splicing factor (SRSF) 1. These XRCC4-dependent, apoptosis-enhancing effects were canceled by depletion of SRSF1 or SR protein kinase (SRPK) 1. In addition, overexpression of SRSF1 in XRCC4-deficient cells restored the normal level of apoptosis, suggesting that SRSF1 functions downstream of XRCC4 in activating CAD. This XRCC4-dependent, SRPK1/SRSF1-mediated regulatory mechanism was conserved in apoptosis in Jurkat human leukemia cells triggered by STS, and by two widely used anti-cancer agents, Paclitaxel and Vincristine. These data imply that the level of XRCC4 expression could be used to predict the effects of apoptosis-inducing drugs in cancer treatment.


Asunto(s)
Apoptosis/efectos de los fármacos , Proteínas de Unión al ADN/genética , Neoplasias/genética , Proteínas Serina-Treonina Quinasas/genética , Factores de Empalme Serina-Arginina/genética , Animales , Núcleo Celular/genética , Fragmentación del ADN/efectos de los fármacos , Reparación del ADN/genética , Desoxirribonucleasas/genética , Regulación Neoplásica de la Expresión Génica , Humanos , Células Jurkat , Ratones , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Paclitaxel/farmacología , Transducción de Señal/efectos de los fármacos , Estaurosporina/farmacología , Vincristina/farmacología
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...