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1.
Front Immunol ; 15: 1399222, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39026679

RESUMEN

Background: Pancreatic adenocarcinoma (PAAD) is a formidable challenge in oncology research, with a complex pathogenesis that requires to be explored. Major Vault Protein (MVP) is the principal structural component of the vault complex, and its expression level is remarkably upregulated in various cancers. Extensive investigations have been conducted to explore the role of MVP in specific cancer contexts, yet the potential molecular mechanisms and biological functions of MVP in PAAD still remain considerably elusive. This study aims to explore the role of MVP as a novel immune-related biomarker in the pathogenesis and clinical treatment of PAAD. Methods: Gene expression data and clinical information were collected from TCGA, GTEx and GEO databases. Survival, prognostic and functional enrichment analysis were employed with R software. Immunological correlation analysis was performed using TIMER2.0, TIDE scores, TISIDB and TISCH. Epigenetic analysis was implemented by MethSurv, CPTAC, UALCAN, and cBioPortal. Drug analysis was conducted using Enrichr and CellMiner. Moreover, cellular experiments, like RNA interference, qRT-PCR, Western blot, cell cycle analysis, cell apoptosis analysis, colony formation assay, transwell assay, and wound healing assay, were performed for verifying the functional properties of MVP in the PAAD progression. Results: We demonstrated an abnormally upregulated expression of MVP in PAAD tissues, which notably correlated with an adverse prognosis in PAAD patients. Functional analysis suggested the conceivable involvement of MVP in immune modulation, and immunotherapy. Additionally, we identified genetic alterations, reduced promoter methylation, and heightened phosphorylation in MVP. We also clarified Suloctidil and Tetradioxin as the most notable potential drugs targeting MVP in PAAD. Moreover, our experimental observations consistently highlighted the significant impact of MVP deficiency on impeding PAAD cell proliferation, inhibiting cell migration, and accelerating cell apoptosis. Interestingly, a potential link between MVP and ERK or AKT pathways was displayed, which opens new avenues for further exploration of the molecular mechanisms of MVP-targeted therapies in PAAD. Conclusions: This study systematically describes MVP as an immune-related biomarker with remarkable potential for predicting the prognosis, tumor progression and immunotherapeutic efficacy in PAAD.


Asunto(s)
Adenocarcinoma , Biomarcadores de Tumor , Movimiento Celular , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Neoplasias Pancreáticas , Partículas Ribonucleoproteicas en Bóveda , Humanos , Neoplasias Pancreáticas/inmunología , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/metabolismo , Partículas Ribonucleoproteicas en Bóveda/genética , Partículas Ribonucleoproteicas en Bóveda/metabolismo , Adenocarcinoma/inmunología , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/patología , Línea Celular Tumoral , Pronóstico , Apoptosis
2.
Sci Rep ; 14(1): 15240, 2024 07 02.
Artículo en Inglés | MEDLINE | ID: mdl-38956386

RESUMEN

Major vault protein (MVP) is the main component of the vault complex, which is a highly conserved ribonucleoprotein complex found in most eukaryotic organisms. MVP or vaults have previously been found to be overexpressed in multidrug-resistant cancer cells and implicated in various cellular processes such as cell signaling and innate immunity. The precise function of MVP is, however, poorly understood and its expression and probable function in lower eukaryotes are not well characterized. In this study, we report that the Atlantic salmon louse expresses three full-length MVP paralogues (LsMVP1-3). Furthermore, we extended our search and identified MVP orthologues in several other ecdysozoan species. LsMVPs were shown to be expressed in various tissues at both transcript and protein levels. In addition, evidence for LsMVP to assemble into vaults was demonstrated by performing differential centrifugation. LsMVP was found to be highly expressed in cement, an extracellular material produced by a pair of cement glands in the adult female salmon louse. Cement is important for the formation of egg strings that serve as protective coats for developing embryos. Our results imply a possible novel function of LsMVP as a secretory cement protein. LsMVP may play a role in structural or reproductive functions, although this has to be further investigated.


Asunto(s)
Copépodos , Partículas Ribonucleoproteicas en Bóveda , Animales , Partículas Ribonucleoproteicas en Bóveda/metabolismo , Copépodos/metabolismo , Salmo salar/parasitología , Salmo salar/metabolismo , Femenino , Filogenia , Secuencia de Aminoácidos
3.
Sci Rep ; 14(1): 17395, 2024 07 29.
Artículo en Inglés | MEDLINE | ID: mdl-39075084

RESUMEN

The constant changes experienced in agricultural activities due to climate change pose a great challenge to melon production. Hence, this research examined the determinants of melon farmers' adaptation strategies to cope with climate change hazards in southern-southern Nigeria. The research ultimately depended on primary data collected by using a set of questionnaires and interviews. The data were obtained from 260 samples retrieved from melon farmers by using multistage sampling techniques. The data were analyzed using the multivariate probit (MVP) model and partial eta squared test. The results of the MVP model showed that age (- 0.009), marital status (0.200), access to information on climate change (0.567) and crop insurance (0.214) were significant at the 0.01 level, while household size (- 0.030) was significant at the 0.05 level and determined the adoption of crop diversification. Educational level (0.012), extension contact (0.138) and access to credit (0.122) were significant at the 0.05 level, while access to information on climate change (0.415) was significant at the 0.01 level and determined the adoption of change in planting dates. Age (- 0.010) and access to information on climate change (0.381) were significant at the 0.01 level, while sex (- 0.139), marital status (0.158) and off-farm income (- 2.3E-7) were significant at the 0.05 level and determined the adoption of mixed farming. Farming experience (0.005) is significant at the 0.05 level, while access to information on climate change (0.529) and crop insurance (0.272) are significant at the 0.01 level and determine the adoption of drought-tolerant crop species. Access to information on climate change (0.536) is significant at the 0.01 level, indicating the adoption of improved crop species. Age (- 0.010), farm size (- 0.085) and crop insurance (0.206) were significant at the 0.05 level, while access to information on climate change (0.353) was significant at the 0.01 level and determined the adoption of off-farm job opportunities. The study recommends the availability and accessibility of credit, climate-smart agricultural practices, and the establishment of public‒private partnerships, among others.


Asunto(s)
Cambio Climático , Cucurbitaceae , Agricultores , Nigeria , Humanos , Cucurbitaceae/fisiología , Masculino , Encuestas y Cuestionarios , Femenino , Adulto , Persona de Mediana Edad , Agricultura/métodos , Productos Agrícolas/crecimiento & desarrollo , Adaptación Fisiológica
4.
Subcell Biochem ; 104: 531-548, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38963499

RESUMEN

Vault ribonucleoprotein particles are naturally designed nanocages, widely found in the eukaryotic kingdom. Vaults consist of 78 copies of the major vault protein (MVP) that are organized in 2 symmetrical cup-shaped halves, of an approximate size of 70x40x40 nm, leaving a huge internal cavity which accommodates the vault poly(ADP-ribose) polymerase (vPARP), the telomerase-associated protein-1 (TEP1) and some small untranslated RNAs. Diverse hypotheses have been developed on possible functions of vaults, based on their unique capsular structure, their rapid movements and the distinct subcellular localization of the particles, implicating transport of cargo, but they are all pending confirmation. Vault particles also possess many attributes that can be exploited in nanobiotechnology, particularly in the creation of vehicles for the delivery of multiple molecular cargoes. Here we review what is known about the structure and dynamics of the vault complex and discuss a possible mechanism for the vault opening process. The recent findings in the characterization of the vaults in cells and in its natural microenvironment will be also discussed.


Asunto(s)
Partículas Ribonucleoproteicas en Bóveda , Partículas Ribonucleoproteicas en Bóveda/metabolismo , Partículas Ribonucleoproteicas en Bóveda/química , Partículas Ribonucleoproteicas en Bóveda/genética , Humanos , Animales , Poli(ADP-Ribosa) Polimerasas/metabolismo , Poli(ADP-Ribosa) Polimerasas/química
5.
Cell Genom ; 4(6): 100582, 2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38870908

RESUMEN

Epiretinal membrane (ERM) is a common retinal condition characterized by the presence of fibrocellular tissue on the retinal surface, often with visual distortion and loss of visual acuity. We studied European American (EUR), African American (AFR), and Latino (admixed American, AMR) ERM participants in the Million Veteran Program (MVP) for genome-wide association analysis-a total of 38,232 case individuals and 557,988 control individuals. We completed a genome-wide association study (GWAS) in each population separately, and then results were meta-analyzed. Genome-wide significant (GWS) associations were observed in all three populations studied: 31 risk loci in EUR subjects, 3 in AFR, and 2 in AMR, with 48 in trans-ancestry meta-analysis. Many results replicated in the FinnGen sample. Several GWS variants associate to alterations in gene expression in the macula. ERM showed significant genetic correlation to multiple traits. Pathway enrichment analyses implicated collagen and collagen-adjacent mechanisms, among others. This well-powered ERM GWAS identified novel genetic associations that point to biological mechanisms for ERM.


Asunto(s)
Membrana Epirretinal , Estudio de Asociación del Genoma Completo , Humanos , Membrana Epirretinal/genética , Femenino , Predisposición Genética a la Enfermedad , Masculino , Población Blanca/genética , Polimorfismo de Nucleótido Simple , Negro o Afroamericano/genética , Sitios Genéticos/genética , Anciano , Estados Unidos/epidemiología , Hispánicos o Latinos/genética , Persona de Mediana Edad
6.
Heliyon ; 10(11): e31894, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38841512

RESUMEN

Land management technology (LMT) adoption is one of Ethiopia's crucial strategies to combat soil depletion and promote agricultural production. However, there is scant information concerning the intensity, interdependent nature, and households' decision to adopt multiple LMTs. Thus, the purpose of this study is to identify factors influencing households' decisions to adopt multiple LMTs and the intensity and interdependency of the technologies in the Goyrie watershed of southern Ethiopia. The data was collected from 291 randomly selected household heads, focus group discussion participants, and key informant interview respondents. The quantitative data was analyzed using descriptive statistics and econometric methods like multivariate probit and ordered probit modeling, while the qualitative data was presented through content analysis. The result indicated that more than half of respondents (67 %) applied one or two LMTs. The highest complementary effects were observed in mixed soil bunds with desho grasses and manure applications. However, soil bunds and fanya-juu, manure application and agroforestry showed interchangeability with one another. Sex, education, family size, landholding size, access to development agents and credit institutions, training, and village membership increased the probability of adopting multiple LMTs, whereas age, land rent, and crop sharing discouraged the likelihood of households' decisions to adopt LMT. The results of the ordered probit model revealed that village membership and contact with extension agents highly encouraged the intensity of LMT adoptions. Thus, policymakers and planners should consider social, institutional, human asset, and technological related factors to increase adoption rates and intensity of land management technologies.

7.
Aging (Albany NY) ; 16(10): 8497-8510, 2024 05 06.
Artículo en Inglés | MEDLINE | ID: mdl-38713157

RESUMEN

Major Vault Protein (MVP) has emerged as a potential prognostic and immunological biomarker in various cancer types. This pan-cancer study aimed to investigate expression of MVP and its correlation with clinical outcomes and immune infiltration across diverse cancer types. We conducted an analysis of extensive transcriptomic and clinical data from publicly available databases. Our findings unveiled a significant association between MVP expression and cancer progression, with higher expression levels predicting poorer overall survival in multiple cancer types. Importantly, MVP expression demonstrated a close relationship with immune infiltration in the tumor microenvironment, showing that higher expression levels were associated with increased immune cell infiltration. We further validated expression of MVP and function in cancer cell lines A549 and AGS. These compelling results suggest that MVP holds promise as a valuable biomarker for prognostic assessment and the development of immunotherapeutic strategies across various cancer types. Consequently, targeting MVP may offer a compelling therapeutic approach in the treatment of human cancers.


Asunto(s)
Biomarcadores de Tumor , Neoplasias , Microambiente Tumoral , Partículas Ribonucleoproteicas en Bóveda , Humanos , Neoplasias/inmunología , Neoplasias/mortalidad , Pronóstico , Microambiente Tumoral/inmunología , Biomarcadores de Tumor/metabolismo , Partículas Ribonucleoproteicas en Bóveda/genética , Partículas Ribonucleoproteicas en Bóveda/metabolismo , Regulación Neoplásica de la Expresión Génica , Línea Celular Tumoral
8.
Cureus ; 16(3): e57062, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38681454

RESUMEN

Fusiform and dolichoectatic aneurysms pose unique challenges in treatment, often requiring alternative approaches compared to saccular aneurysms. Microsurgical options like clipping or a bypass can be difficult, leading to the advancement of endovascular techniques. Flow-diverting stents and vessel sacrifice with detachable coils have shown efficacy in reconstruction. The MVP® Micro Vascular Plug System (Medtronic, Minneapolis, Minnesota, USA) offers a resheathable plug for vessel occlusion through electrolytic detachment. This case report illustrates the supplementary application of MVP® subsequent to flow diverter (FD) stenting, resulting in the effective endovascular management of a fusiform aneurysm affecting both vertebral arteries (VA), following unsuccessful coil vessel sacrifice treatment. A 61-year-old female presented with an unruptured fusiform aneurysm in the bilateral vertebral arteries (VAs). Treatment included a flow diverter in the right VA and vessel sacrifice in the left VA using Onyx-18 and coils. Despite initial success, left V4 segment recanalization occurred. Endovascular treatment, deploying two devices and additional coils using the MVP®, halted the flow. Follow-up showed left VA occlusion and reconstruction of the treated right VA, with the patient being discharged without deficits. This case demonstrates a unique approach using MVP® alongside a flow diverter (a PipelineTM Embolization Device (PED), Medtronic) for the treatment of a V4 segment fusiform aneurysm. This innovative technique is an alternative when conventional coil embolization for vessel sacrifice fails. The MVP®'s ease of use and precise delivery render it a feasible and efficacious alternative for treating complex aneurysms.

9.
Heliyon ; 10(4): e26758, 2024 Feb 29.
Artículo en Inglés | MEDLINE | ID: mdl-38434071

RESUMEN

Although urban agriculture (UA) can aid economic development, food inflation, unemployment, and nutritional insecurity often necessitate urban households to engage in various agricultural practices. Hence, the study aimed to identify UA practices adopted and their determinants in the Eastern Haraghe zone of the Oromia region and Dire Dawa City Administration, Eastern Ethiopia. Data was collected from 385 randomly selected urban households using a semi-structured questionnaire. Descriptive statistics and a Multivariate Probit (MVP) model were used to analyze the data. The results of the MVP model reveal that sex, age, education level, land size, extension contact, credit access, community group participation, training, and household non-farm income significantly influenced vegetable farming adoption. On the other hand, livestock production adoption was also affected by factors such as sex, land size, perception, credit access, farming experience, community group participation, market distance, training, and non-farm income. Crop-fruit production adoption was also influenced by factors like age, perception, farming experience, market distance, training, and dependency ratio. Improving the ability to use the land for UA purposes, empowering female-headed households, improving livestock breeds, creating awareness through short-term training, and improving credit accessibility are important recommendations to enhance the adoption of UA practices in the study areas.

10.
Arch Gynecol Obstet ; 309(5): 2167-2173, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38503849

RESUMEN

OBJECTIVE: The purpose of this study is to compare the clinical efficacy of oral dydrogesterone and micronized vaginal progesterone (MVP) gel during the first HRT-FET cycle. METHODS: A retrospective cohort study based on a total of 344 women undergoing their first HRT-FET cycles without Gonadotropin-Releasing Hormone agonist (GnRH-a) pretreatment was conducted. All the cycles were allocated to two groups in the reproductive medical center at the University of Hong Kong-Shenzhen Hospital. One group (n = 193) received oral dydrogesterone 30 mg/d before embryo transfer, while the other group (n = 151) received MVP gel 180 mg/d. RESULTS: The demographics and baseline characteristics of two groups were comparable. We found no statistically significant difference in live birth rate (24.35% vs. 31.13%, P = 0.16), clinical pregnancy rate (34.72% vs. 36.42%, P = 0.74), embryo implantation rate (25.09% vs. 28.36%, P = 0.43), positive pregnancy rate (42.49% vs 38.41%, P = 0.45), miscarriage rate (9.33% vs 3.97%, P = 0.05), or ectopic pregnancy rate (0.52% vs. 0.66%, P = 0.86) between the oral dydrogesterone group and MVP gel group. In the multivariate logistic regression analysis for covariates, medication used for luteal support was not associated with live birth rate (OR = 0.73, 95% CI: 0.32-1.57, P = 0.45). And the different luteal support medication did not have a significant positive association with the live birth rate in the cycles with day 2 embryo transferred (OR = 1.39, 95% CI:0.66-2.39, P = 0.39) and blastocyst transferred (OR = 1.31 95% CI:0.64-2.69, P = 0.46). CONCLUSION: 30 mg/d oral dydrogesterone and 180 mg/d MVP gel revealed similar reproductive outcomes in HRT-FET cycles in the study.


Asunto(s)
Didrogesterona , Progesterona , Embarazo , Femenino , Humanos , Progesterona/uso terapéutico , Estudios Retrospectivos , Índice de Embarazo , Transferencia de Embrión , Luteína
11.
Patient Educ Couns ; 123: 108203, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38359588
13.
J Electrocardiol ; 82: 125-130, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38128157

RESUMEN

BACKGROUND: P-wave indices reflect atrial abnormalities contributing to atrial fibrillation (AF). We aimed to assess a comprehensive set of P-wave characteristics for prediction of incident AF in a population-based setting. METHODS: Malmö Preventative Project (MPP) participants were reexamined in 2002-2006 with electrocardiographic (ECG) and echocardiographic examinations and followed for 5 years. AF-free subjects (n = 983, age 70 ± 5 years, 38% females) with sinus rhythm ECGs were included in the study. ECGs were digitally processed using the Glasgow algorithm. P-wave duration, axis, dispersion, P-terminal force in lead V1 and interatrial block (IAB) were evaluated. ECG risk score combining the morphology, voltage and length of P-wave (MVP score) was calculated. New-onset diagnoses of AF were obtained from nation-wide registers. RESULTS: During follow up, 66 patients (7%) developed AF. After adjustment for age and gender, the independent predictors of AF were abnormal P-wave axis > 75° (HR 1.63 CI95% 1.95-11.03) and MVP score 4 (HR 6.17 CI 95% 1.76-21.64), both correlated with LA area: Person r - 0.146, p < 0.001 and 0.192, p < 0.001 respectively. Advanced IAB (aIAB) with biphasic P-wave morphology in leads III and aVF was the most prevalent variant of aIAB and predicted AF in a univariate model (HR 2.59 CI 95% 1.02-6.58). CONCLUSION: P-wave frontal axis and MVP score are ECG-based AF predictors in the population-based cohort. Our study provides estimates for prevalence and prognostic importance of different variants of aIAB, providing a support to use biphasic P-wave morphology in lead aVF as the basis for aIAB definition.


Asunto(s)
Fibrilación Atrial , Femenino , Humanos , Anciano , Masculino , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/epidemiología , Electrocardiografía , Atrios Cardíacos , Ecocardiografía , Bloqueo Interauricular/diagnóstico , Bloqueo Interauricular/epidemiología
14.
Redox Biol ; 68: 102962, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38029455

RESUMEN

Pancreatic ductal adenocarcinoma (PDA) cells reprogram both mitochondrial and lysosomal functions to support growth. At the same time, this causes significant dishomeostasis of free radicals. While this is compensated by the upregulation of detoxification mechanisms, it also represents a potential vulnerability. Here we demonstrate that PDA cells are sensitive to the inhibition of the mevalonate pathway (MVP), which supports the biosynthesis of critical antioxidant intermediates and protect from ferroptosis. We attacked the susceptibility of PDA cells to ferroptotic death with selenorganic compounds, including dibenzyl diselenide (DBDS) that exhibits potent pro-oxidant properties and inhibits tumor growth in vitro and in vivo. DBDS treatment induces the mobilization of iron from mitochondria enabling uncontrolled lipid peroxidation. Finally, we showed that DBDS and statins act synergistically to promote ferroptosis and provide evidence that combined treatment is a viable strategy to combat PDA.


Asunto(s)
Ferroptosis , Neoplasias Pancreáticas , Selenio , Humanos , Páncreas , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/patología , Peroxidación de Lípido , Neoplasias Pancreáticas
15.
Front Neurol ; 14: 1058697, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37560453

RESUMEN

Background and purpose: Mitral valve prolapse (MVP) has been associated with an increased risk of ischemic stroke. Older age, thicker mitral leaflets, and significant mitral regurgitation (MR) leading to atrial fibrillation have been traditionally considered risk factors for ischemic stroke in MVP. However, specific risk factors for MVP-stroke subtypes are not well defined. The aim of this study is to evaluate clinical and echocardiographic parameters, including left atrial (LA) function, in MVP with cryptogenic (C) vs. non-cryptogenic (NC) stroke. Methods: In this case-control matched study, MVPs were identified in consecutive echocardiograms obtained after a stroke from January 2013 to December2016 at the University of California, San Francisco. MVP was defined as leaflet displacement ≥2 mm in the parasternal long-axis view at end-systole. Age/gender matched MVPs without stroke and healthy controls without MVP were also identified. We analyzed LA end-systolic/diastolic volume index, emptying fraction (LAEF), function index (LAFI), and global longitudinal strain in all MVPs and controls. We also measured left ventricular (LV) volume indexes, mass index, ejection fraction (EF), degree of MR and leaflet thickness. Results: We identified a total of 30 MVPs (age 70 ± 12, 50% females) with stroke (11 with C- and 19 with NC-stroke), 20 age/gender matched MVPs without a stroke and 16 controls. MVPs without stroke had lower BMI, less hypertension but more MR (≥moderate in 45% vs. 17%), more abnormal LA function (lower LAEF, LAFI) and larger LV volumes/mass (all p < 0.05) when compared to MVPs with stroke. Leaflet thickness was overall mild (<3 mm) and similar in the 2 groups. Within the MVP stroke group, NC-stroke had higher BMI, more hypertension and more atrial fibrillation compared to C-stroke. In the variables tested, patients with C-stroke did not differ from controls. Conclusions: MVP-related MR may be protective against stroke despite abnormal LA function. Risk of NC-stroke in MVP is related to common stroke risk factors rather than mitral valve leaflet thickness. The etiology of C-stroke in MVP warrants further studies.

16.
Pediatr Int ; 65(1): e15582, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37518971

RESUMEN

BACKGROUND: Pectus anomalies constitute 95% of chest anomalies. Pectus carinatum (PC) and excavatum (PE) are often asymptomatic in childhood. However, symptoms and signs such as chest pain, dyspnea, and mitral valve prolapse (MVP) can be seen in pectus anomalies. Demographic characteristics and accompanying cardiac signs in children with pectus deformity were investigated. METHODS: In this study, the clinical findings for children with pectus deformity, and the incidence of MVP and other concomitant heart diseases detected in echocardiographic examinations were evaluated. RESULTS: Eighty-two children with PE, 27 with PC, and 107 healthy children were included in this study. In the echocardiographic examination of PE, PC patients, and healthy children, MVP was detected with frequencies of 25%, 33%, and 2% respectively. CONCLUSIONS: The study showed that pectus anomalies were associated with an increased incidence of MVP. All patients with pectus deformity should therefore undergo a screening echocardiogram in adolescence to assess for the presence of MVP.


Asunto(s)
Tórax en Embudo , Prolapso de la Válvula Mitral , Pared Torácica , Adolescente , Humanos , Niño , Prolapso de la Válvula Mitral/diagnóstico , Prolapso de la Válvula Mitral/diagnóstico por imagen , Pared Torácica/diagnóstico por imagen , Tórax en Embudo/complicaciones , Tórax en Embudo/diagnóstico , Tórax en Embudo/epidemiología , Incidencia , Corazón
17.
Int Immunopharmacol ; 120: 110313, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37267856

RESUMEN

OBJECTIVE: Major vault protein (MVP) is vital in various macrophage-related inflammatory diseases. However, the effects of MVP on macrophage polarization during fracture repair are still unknown. METHODS: We used Mvpflox/floxLyz2-Cre mice (myeloid-specific MVP gene knockout, abbreviated as MacKO) and Mvpflox/flox (abbreviated as MacWT) mice to compare their fracture healing phenotype. Next, we traced the changes in macrophage immune status in vivo and in vitro. We further explored the effects of MVP on osteogenesis and osteoclastogenesis. Finally, we re-expressed MVP in MacKO mice to confirm the role of MVP in fracture healing. RESULTS: The lack of MVP in macrophages impaired their transition from a pro-inflammatory to an anti-inflammatory phenotype during fracture repair. The increased secretion of pro-inflammatory cytokines by macrophages promoted their osteoclastic differentiation and impaired BMSC osteogenic differentiation, ultimately leading to impaired fracture repair in MacKO mice. Last, adeno-associated virus (AAV)-Mvp tibial injection significantly promoted fracture repair in MacKO mice. CONCLUSIONS: Our findings showed MVP has a previously unknown immunomodulatory role in macrophages during fracture repair. Targeting macrophage MVP may represent a novel therapeutic method for fracture treatment.


Asunto(s)
Macrófagos , Osteogénesis , Ratones , Animales , Partículas Ribonucleoproteicas en Bóveda/metabolismo , Partículas Ribonucleoproteicas en Bóveda/farmacología , Citocinas/metabolismo
18.
Front Cardiovasc Med ; 10: 1140216, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37123476

RESUMEN

Objectives: This study sought to assess the value of myocardial deformation using strain echocardiography in patients with mitral valve prolapse (MVP) and severe ventricular arrhythmia and to evaluate its impact on rhythmic risk stratification. Background: MVP is a common valvular affection with an overly benign course. Unpredictably, selected patients will present severe ventricular arrhythmia. Methods: Patients with MVP as the only cause of aborted SCD (MVP-aSCD: ventricular fibrillation and monomorphic and polymorphic ventricular tachycardia) with no other obvious reversible cause were identified. Nonconsecutive patients referred for the echocardiographic evaluation of MVP were enrolled as a control cohort and dichotomized according to the presence or absence of premature ventricular contractions (MVP-PVC or MVP-No PVC, respectively). All patients had a comprehensive strain assessment of mechanical dispersion (MD), postsystolic shortening, and postsystolic index (PSI). Results: A total of 260 patients were enrolled (20 MVP-aSCD, 54 MVP-PVC, and 186 MVP-No PVC). Deformation pattern discrepancies were observed with a higher PSI value in MVP-aSCD than that in MVP-PVC (4.6 ± 2.0 vs. 2.9 ± 3.7, p = 0.014) and a higher MD value than that in MVP-No PVC (46.0 ± 13.0 vs. 36.4 ± 10.8, p = 0.002). In addition, PSI and MD increased the prediction of severe ventricular arrhythmia on top of classical risk factors in MVP. Net reclassification improvement was 61% (p = 0.008) for PSI and 71% (p = 0.001) for MD. Conclusions: In MVP, myocardial deformation analysis with strain echocardiography identified specific contraction patterns with postsystolic shortening leading to increased values of PSI and MD, translating the importance of mitral valve-myocardial interactions in the arrhythmogenesis of severe ventricular arrhythmia. Strain echocardiography may provide important implications for rhythmic risk stratification in MVP.

19.
Echocardiography ; 40(8): 862-865, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37138500

RESUMEN

Adequate grading of mitral regurgitation (MR) in patients with mitral valve prolapse (MVP) in the presence of mid-late systolic jets can represent a major challenge. In this entity, jets are commonly overestimated by echocardiography. Correct quantification is crucial and highly relevant for the further management and prognosis of these oftentimes young patients. This case points out potential pitfalls and underlines the importance to systematically include qualitative, quantitative, and semi-quantitative parameters into the echocardiographic assessment.


Asunto(s)
Insuficiencia de la Válvula Mitral , Prolapso de la Válvula Mitral , Humanos , Prolapso de la Válvula Mitral/complicaciones , Prolapso de la Válvula Mitral/diagnóstico por imagen , Insuficiencia de la Válvula Mitral/complicaciones , Insuficiencia de la Válvula Mitral/diagnóstico por imagen , Ecocardiografía , Pronóstico , Soplos Cardíacos
20.
Heliyon ; 9(3): e14563, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36967950

RESUMEN

This study examined the socio-economic factors influencing choice of climate change adaptation practices and the effects of these practices on cassava productivity in Nigeria. Using a multi-stage sampling technique, structured questionnaire was used to survey 100 cassava farmers. The result was analyzed with a multivariate probit and generalized linear regression models. The result showed male dominance (78%) in cassava farming and the mean age of the cassava farmers was 45.46 ± 9.36 years. About 66% of the farmers belonged to cooperative associations and 67% had access to credit facilities. The multivariate model revealed that age of farmers, gender, education qualification, primary occupation, total income, membership of cooperative associations, farming objectives, farming experience, access to extension visit, access to credit, type of land ownership, farm size and climatic conditions significantly influenced choice of climate change adaptation practices among cassava farmers. The generalized linear model identified farming system, multiple crop types/improved crop varieties used, crop diversification, organic manuring, multiple planting dates, use of alternate fallowing, education and credit access to significantly affect cassava productivity. The study concluded that, eco-friendly methods for adapting to climate change increase cassava productivity. Thus, cassava farmers should be trained on the use of best climate change adaptation practices that can boost cassava productivity. In order to practice climate smart farming, it is important to stress the usage of organic manure and alternate fallowing.

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