Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 25
Filtrar
Más filtros

Banco de datos
Tipo del documento
Intervalo de año de publicación
1.
mBio ; : e0243324, 2024 Oct 07.
Artículo en Inglés | MEDLINE | ID: mdl-39373507

RESUMEN

The Aedes aegypti mosquito plays a critical role in the transmission of viral diseases, including Zika virus, which poses significant public health challenges. Understanding the complex interactions between mosquitoes and viruses is paramount for the development of effective control strategies. In this study, we demonstrate that silencing the A. aegypti adiponectin receptor-like protein (AaARLP) results in a reduction of Zika virus infection. Transcriptomic analysis identified alterations in several trypsin genes and further revealed that AaARLP-knockdown mosquitoes had diminished trypsin activity. Moreover, silencing of selected trypsins resulted in a similar delay in Zika virus infection in mosquitoes, further highlighting the connection between the AaARLP and trypsin. Overall, our findings demonstrate that AaARLP signaling is important for Zika virus infection of A. aegypti. IMPORTANCE: Arboviruses pose a significant threat to public health, with mosquitoes, especially Aedes aegypti, being a major vector for their transmission. Gaining insight into the complex interaction between mosquitoes and viruses is essential to build successful control strategies. In this study, we identified a novel pathway connecting the A. aegypti adiponectin receptor-like protein and its association with trypsin, key enzymes involved in blood digestion. Furthermore, we demonstrated the significance of signaling via the adiponectin receptor-like protein in virus infection within the mosquito. Together, our discoveries illuminate mosquito metabolic pathways essential in viral infection.

2.
iScience ; 27(7): 110353, 2024 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-39055935

RESUMEN

The Aedes aegypti midgut is crucial for blood digestion, nutrition, reproduction, and pathogen interaction. Using single-cell RNA sequencing, we explored virus infection and transcriptomic changes at the cellular level. We identified 12 distinct cell clusters in the Ae. aegypti midgut post-Zika virus infection, including intestinal stem cells, enteroblasts, enteroendocrine cells (EE), and enterocytes (ECs). The virus was found mainly in specific subsets of ECs and EE. Infection altered transcriptional profiles related to metabolism, signaling, and immune responses. Functional studies highlighted three significantly differentially expressed genes in infected cells. Notably, silencing apolipophorin III reduced virus RNA copy number in the midgut, emphasizing the role of specific genes in viral infection. These findings enhance our understanding of mosquito midgut cell processes during Zika virus infection and suggest potential targets for vector control.

3.
Aging Cell ; 23(4): e14103, 2024 04.
Artículo en Inglés | MEDLINE | ID: mdl-38361361

RESUMEN

S-adenosylmethionine (SAM), generated from methionine and ATP by S-adenosyl methionine synthetase (SAMS), is the universal methyl group donor required for numerous cellular methylation reactions. In Caenorhabditis elegans, silencing sams-1, the major isoform of SAMS, genetically or via dietary restriction induces a robust mitochondrial unfolded protein response (UPRmt) and lifespan extension. In this study, we found that depleting SAMS-1 markedly decreases mitochondrial SAM levels. Moreover, RNAi knockdown of SLC-25A26, a carrier protein responsible for transporting SAM from the cytoplasm into the mitochondria, significantly lowers the mitochondrial SAM levels and activates UPRmt, suggesting that the UPRmt induced by sams-1 mutations might result from disrupted mitochondrial SAM homeostasis. Through a genetic screen, we then identified a putative mitochondrial tRNA methyltransferase TRMT-10C.2 as a major downstream effector of SAMS-1 to regulate UPRmt and longevity. As disruption of mitochondrial tRNA methylation likely leads to impaired mitochondrial tRNA maturation and consequently reduced mitochondrial translation, our findings suggest that depleting mitochondrial SAM level might trigger UPRmt via attenuating protein translation in the mitochondria. Together, this study has revealed a potential mechanism by which SAMS-1 regulates UPRmt and longevity.


Asunto(s)
Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Animales , Caenorhabditis elegans/metabolismo , Longevidad/genética , S-Adenosilmetionina/metabolismo , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Mitocondrias/metabolismo , Respuesta de Proteína Desplegada , ARN de Transferencia/metabolismo
4.
J Neurosurg Spine ; 40(6): 773-781, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38518295

RESUMEN

OBJECTIVE: This retrospective study was designed to evaluate the incidence and predisposing factors of heterotopic ossification (HO) after cervical disc arthroplasty (CDA) with a specific implant at 1 and 2 levels, and to investigate the biomechanical effects related to HO. The study goal was to identify ways to reduce the likelihood of HO formation after surgery. METHODS: The study included patients who underwent only 1- or 2-level CDA with the Baguera C disc between November 2014 and December 2021 at a single medical center. All patients were operated on by the same neurosurgeon. The surgical indication included 1-level or 2-level disc herniation between C3 and C7 with radiculopathy, myelopathy, or both, with minimal spondylosis. The various factors were assessed by evaluating plain radiographs and cervical CT scans. The presence of HO was evaluated at different intervals postsurgery, and HO severity was graded using the McAfee classification. RESULTS: Of 107 patients who underwent CDA, 47 (43.9%) had HO at 63 of 171 levels (36.8%). Most cases with HO were grade 1, and no grade 4 was observed. Statistically significant risk factors for HO were the length of endplate coverage ratio and inferior anterior residual exposed endplate (AREE); sex, age, implant height and width, shell angle, and pre- and postoperative functional spinal unit (FSU) angle were not significant. More AREE and greater kyphotic postoperative FSU angle in the flexion position were significant factors differentiating HO grades 0 and 1 from grades 2 and 3. Furthermore, the non-HO group showed a trend of higher range of motion at any postoperative time compared to the HO group, especially at 1 month after surgery. CONCLUSIONS: The HO incidence after CDA was correlated with the residual length of endplate coverage and inferior AREE. Additionally, the AREE and kyphotic postoperative FSU angle in the flexion position were associated with HO grade progression. Patients with HO also showed a trend of lower range of motion at 1 month after surgery. Using an adequately sized implant and encouraging neck motion may help prevent HO development and progression.


Asunto(s)
Vértebras Cervicales , Osificación Heterotópica , Humanos , Osificación Heterotópica/etiología , Osificación Heterotópica/epidemiología , Osificación Heterotópica/diagnóstico por imagen , Femenino , Masculino , Factores de Riesgo , Vértebras Cervicales/cirugía , Vértebras Cervicales/diagnóstico por imagen , Incidencia , Persona de Mediana Edad , Estudios Retrospectivos , Adulto , Desplazamiento del Disco Intervertebral/cirugía , Reeemplazo Total de Disco/efectos adversos , Reeemplazo Total de Disco/métodos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Disco Intervertebral/cirugía , Disco Intervertebral/diagnóstico por imagen , Anciano , Artroplastia/efectos adversos , Artroplastia/métodos , Radiculopatía/cirugía , Radiculopatía/etiología , Radiculopatía/epidemiología
5.
J Clin Med ; 13(12)2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38929945

RESUMEN

Objectives: Cervical disc herniation (CDH) leads to pain, numbness, and potential disability. Percutaneous endoscopic cervical discectomy (PECD) offers an anterior or posterior approach. This study aims to compare postoperative disc height and angle changes one year after PECD, considering both approaches. Methods: We retrospectively reviewed the data from patients with CDH who underwent PECD from October 2017 to July 2022. Cervical disc height was measured using the preoperative and one-year postoperative magnetic resonance imaging (MRI) examinations. Lordotic angle (LA), global alignment angle (GAA), segmental alignment angle (SAA), and slippage distance (SD) at the surgical level were measured on radiographs in the neutral, flexion, and extension positions. Results: Thirty-eight patients who underwent posterior PECD (PPECD) and five patients who underwent anterior PECD (APECD) were included in the evaluation. The mean age of the patients was 47.4 years (range: 29-69 years). There was a significant difference in the preoperative and one-year postoperative GAA and SAA in extension in the PPECD group (p = 0.003 and 0.031, respectively). The mean decreased disc height one-year postoperative was 1.30 mm in the APECD group and 0.3 mm in the PPECD group by MRI. A significant disc height decrease was observed in the APECD group (p < 0.001). Conclusions: Treating CDH with PPECD or APECD is feasible, as it can relieve symptoms and reduce disability. Stability remained unaffected during the first year after surgery, even though there was an increase in angulation during extension. Despite a significant decrease in disc space following APECD, patients reported significant symptom improvement and no new symptoms.

6.
J Clin Med ; 13(2)2024 Jan 19.
Artículo en Inglés | MEDLINE | ID: mdl-38276088

RESUMEN

BACKGROUND: This study evaluates the impact of hybrid dynamic stabilization using the Dynesys-Transition-Optima (DTO) system on adjacent segment disease (ASD) in lumbar spinal stenosis patients with spondylolisthesis. METHODS: From 2012 to 2020, 115 patients underwent DTO stabilization at a single center by a single neurosurgeon. After exclusions for lack of specific stabilization and incomplete data, 31 patients were analyzed. Follow-up was conducted at 6, 12, and 24 months postoperatively, assessing disc height, listhesis distance, and angular motion changes at L2-L3, L3-L4, and L5-S1. RESULTS: L3-L4 segment (the index level), demonstrated a delayed increase in listhesis distance, contrasting with earlier changes in other segments. At two years, L3-L4 exhibited less increase in listhesis distance and less disc height reduction compared to L2-L3 and L5-S1. Notably, the L3-L4 segment showed a significant reduction in angular motion change over two years. CONCLUSIONS: In conclusion, while ASD was not significantly prevented, the study indicates minor and delayed degeneration at the index level. The L3-L4 segment experienced reduced angular change in motion, suggesting a potential benefit of DTO in stabilizing this specific segment.

7.
J Clin Med ; 13(6)2024 Mar 10.
Artículo en Inglés | MEDLINE | ID: mdl-38541814

RESUMEN

Background: Cervical disc arthroplasty (CDA) is currently used instead of fusion to preserve cervical spine motion. Cervical implant subsidence is a potential complication after CDA. Methods: Radiological measurements were recorded via patient anteroposterior and lateral radiographs in the neutral position. Subsidence was defined as a decrease of 3 mm or more in functional spinal unit height (FSUH) from which was measured on a post-operative (OP) radiograph. Results: This study included 104 patients who underwent 153 CDA levels with the Bryan Disc. Approximately one-quarter of the implants (22.9%) showed subsidence. Binary logistic regression analysis indicated that pre-OP mean disc height (DH) was identified as an independent risk factor for subsidence in multivariate analysis (0.151, 95% Confidence Interval 0-0.073, p = 0.018). Receiver operating characteristic curve analysis (area under the curve = 0.852, sensitivity 84.7%, specificity 77.1%) revealed a cut-off value of 4.48 mm for pre-OP Mean-DH in the risk for implant subsidence. Conclusions: In this study, the subsidence rate significantly increased when the implants were oversized beyond a pre-OP Mean-DH of approximately >4 mm. Moreover, the implant subsidence incidence was higher than that reported in previous studies. This is possibly due to endplate over-preparation or disc space over-distraction during placement at the same height as the Bryan Disc (8.5 mm).

8.
Sci Immunol ; 9(98): eadk9872, 2024 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-39121194

RESUMEN

The Aedes aegypti mosquito is a vector of many infectious agents, including flaviviruses such as Zika virus. Components of mosquito saliva have pleomorphic effects on the vertebrate host to enhance blood feeding, and these changes also create a favorable niche for pathogen replication and dissemination. Here, we demonstrate that human CD47, which is known to be involved in various immune processes, interacts with a 34-kilodalton mosquito salivary protein named Nest1. Nest1 is up-regulated in blood-fed female A. aegypti and facilitates Zika virus dissemination in human skin explants. Nest1 has a stronger affinity for CD47 than its natural ligand, signal regulatory protein α, competing for binding at the same interface. The interaction between Nest1 with CD47 suppresses phagocytosis by human macrophages and inhibits proinflammatory responses by white blood cells, thereby suppressing antiviral responses in the skin. This interaction elucidates how an arthropod protein alters the human response to promote arbovirus infectivity.


Asunto(s)
Aedes , Piel , Virus Zika , Aedes/inmunología , Aedes/virología , Animales , Humanos , Piel/inmunología , Piel/virología , Virus Zika/inmunología , Virus Zika/fisiología , Femenino , Proteínas de Insectos/inmunología , Infección por el Virus Zika/inmunología , Proteínas y Péptidos Salivales/inmunología , Mosquitos Vectores/inmunología , Mosquitos Vectores/virología , Antígeno CD47
9.
Cancer Gene Ther ; 31(6): 894-903, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38418842

RESUMEN

This study utilized Next-Generation Sequencing (NGS) to explore genetic determinants of survival duration in Glioblastoma Multiforme (GBM) patients. We categorized 30 primary GBM patients into two groups based on their survival periods: extended survival (over two years, N = 17) and abbreviated survival (under two years, N = 13). For identifying pathogenic or likely pathogenic variants, we leveraged the ClinVar database. The cohort, aged 23 to 66 (median: 53), included 17 patients in Group A (survival >2 years, 10 males, 7 females), and 13 patients in Group B (survival <2 years, 8 males, 5 females), with a 60% to 40% male-to-female ratio. Identified mutations included CHEK2 (c.1477 G > A, p.E493K), IDH1 (c.395 G > A, p.R132H), and TP53 mutations. Non-coding regions exhibited variants in the TERT promoter (c.-146C > T, c.-124C > T) and TP53 RNA splicing site (c.376-2 A > C, c.376-2 A > G). While Group A had more mutations, statistical significance wasn't reached, likely due to sample size. Notably, TP53, and ATR displayed a trend toward significance. Surprisingly, TP53 mutations were more prevalent in Group A, contradicting Western findings on poorer GBM prognosis. In Taiwanese GBM patients, bevacizumab usage is linked to improved survival rates, affirming its safety and effectiveness. EGFR mutations are infrequent, suggesting potential distinctions in carcinogenic pathways. Further research on EGFR mutations and amplifications is essential for refining therapeutic approaches. TP53 mutations are associated with enhanced survival, but their functional implications necessitate detailed exploration. This study pioneers genetic analysis in Taiwanese GBM patients using NGS, advancing our understanding of their genetic landscape.


Asunto(s)
Glioblastoma , Mutación , Humanos , Glioblastoma/genética , Glioblastoma/mortalidad , Masculino , Femenino , Persona de Mediana Edad , Adulto , Taiwán/epidemiología , Anciano , Estudios Retrospectivos , Adulto Joven , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/mortalidad , Secuenciación de Nucleótidos de Alto Rendimiento , Pronóstico
10.
Parasit Vectors ; 16(1): 166, 2023 May 19.
Artículo en Inglés | MEDLINE | ID: mdl-37208697

RESUMEN

BACKGROUND: Vector competence in Aedes aegypti is influenced by various factors. Crucial new control methods can be developed by recognizing which factors affect virus and mosquito interactions. METHODS: In the present study we used three geographically distinct Ae. aegypti populations and compared their susceptibility to infection by dengue virus serotype 2 (DENV-2). To identify any differences among the three mosquito populations, we evaluated expression levels of immune-related genes and assessed the presence of microbiota that might contribute to the uniqueness in their vector competence. RESULTS: Based on the results from the DENV-2 competence study, we categorized the three geographically distinct Ae. aegypti populations into a refractory population (Vilas do Atlântico), a susceptible population (Vero) and a susceptible but low transmission population (California). The immune-related transcripts were highly expressed in the California population but not in the refractory population. However, the Rel-1 gene was upregulated in the Vilas do Atlântico population following ingestion of a non-infectious blood meal, suggesting the gene's involvement in non-viral responses, such as response to microbiota. Screening of the bacteria, fungi and flaviviruses revealed differences between populations, and any of these could be one of the factors that interfere with the vector competence. CONCLUSIONS: The results reveal potential factors that might impact the virus and mosquito interaction, as well as influence the Ae. aegypti refractory phenotype.


Asunto(s)
Aedes , Virus del Dengue , Dengue , Microbiota , Animales , Virus del Dengue/genética , Aedes/fisiología , Mosquitos Vectores/fisiología
11.
Pathogens ; 12(3)2023 Feb 23.
Artículo en Inglés | MEDLINE | ID: mdl-36986293

RESUMEN

Arthropod-borne viruses present important public health challenges worldwide. Viruses such as DENV, ZIKV, and WNV are of current concern due to an increasing incidence and an expanding geographic range, generating explosive outbreaks even in non-endemic areas. The clinical signs associated with infection from these arboviruses are often inapparent, mild, or nonspecific, but occasionally develop into serious complications marked by rapid onset, tremors, paralysis, hemorrhagic fever, neurological alterations, or death. They are predominately transmitted to humans through mosquito bite, during which saliva is inoculated into the skin to facilitate blood feeding. A new approach to prevent arboviral diseases has been proposed by the observation that arthropod saliva facilitates transmission of pathogens. Viruses released within mosquito saliva may more easily initiate host invasion by taking advantage of the host's innate and adaptive immune responses to saliva. This provides a rationale for creating vaccines against mosquito salivary proteins, especially because of the lack of licensed vaccines against most of these viruses. This review aims to provide an overview of the effects on the host immune response by the mosquito salivary proteins and how these phenomena alter the infection outcome for different arboviruses, recent attempts to generate mosquito salivary-based vaccines against flavivirus including DENV, ZIKV, and WNV, and the potential benefits and pitfalls that this strategy involves.

12.
J Clin Neurosci ; 114: 97-103, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37352684

RESUMEN

OBJECTIVES: Heterotopic ossification (HO), a major cause of dysfunction after disc arthroplasty (CDA). The aim of this study was to determine the cut value of the residual exposed endplate (REE) ratio and to predict the development of posterior HO after Bryan CDA. METHODS: This retrospective study investigated the relationship between the REE ratio and posterior HO formation after Bryan CDA. Consecutive adult patients who underwent 1- or 2-level Bryan CDA by a single neurosurgeon between 2006 and 2016 with at least two years follow-up were included. Postoperative radiographic analysis and measurement were performed to obtain the REE ratio and the HO grade. RESULTS: Of 249 patients with 384 surgical levels who underwent Bryan CDA during the study period, 114 (45.8 %) received 1-level CDA and 135 (54.2 %) received 2-level CDA. Lateral radiographs showed that 169 implants (44 %) had posterior HOs in all grades after two years or more of follow up and 14 implants (3.64 %) had severe HO (McAfee grades 3 and 4). In 329 implants (85.7 %), a comparison of radiographs to CT examination of HO grading showed a substantial relationship. Using area under the curve (AUC) analysis, a REE ratio >9 %, with 65.1 % sensitivity and 86.5 % specificity, was the cut point for posterior HO formation. CONCLUSIONS: REE is highly correlated with the development of postoperative posterior HO after Bryan CDA, regardless of the level of implantation. An undersized implant causing a REE ratio >9 % is a predictor of postoperative posterior HO formation after cervical Bryan CDA.


Asunto(s)
Degeneración del Disco Intervertebral , Disco Intervertebral , Osificación Heterotópica , Adulto , Humanos , Resultado del Tratamiento , Estudios Retrospectivos , Vértebras Cervicales/diagnóstico por imagen , Vértebras Cervicales/cirugía , Artroplastia/efectos adversos , Osificación Heterotópica/diagnóstico por imagen , Osificación Heterotópica/etiología , Complicaciones Posoperatorias/diagnóstico por imagen , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/cirugía , Degeneración del Disco Intervertebral/cirugía , Disco Intervertebral/diagnóstico por imagen , Disco Intervertebral/cirugía
13.
Biomed Res Int ; 2023: 8010223, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36794256

RESUMEN

Objectives: The objectives of this study were to identify the risk factors and incidence of anterior bone loss (ABL) after Baguera C cervical disc arthroplasty (CDA) and identify whether design differences in artificial discs affect ABL. Methods: In this retrospective radiological review of patients who underwent single-level Baguera C CDA in a medical center, the extent of ABL and the following radiological parameters were recorded: global and segmental alignment angle, lordotic angle (or functional spinal unit angle), shell angle, global range of motion (ROM), and ROM of the index level. ABL at the index level was grade 0-2. Grade 0 was defined as no remodeling, grade 1 as spur disappearance or mild change in body contour, and grade 2 as obvious bone regression with Baguera C Disc exposure. Results: Combining grade 1 and grade 2, ABL was found in 56 upper adjacent vertebrae and 52 lower adjacent vertebrae of the 77 patients. Only 18 patients (23.4%) had no ABL. Shell angle differed significantly between ABL grades of both the upper and lower adjacent level: 0.0° in grade 0 and 1 ABL vs. 2.0° in grade 2 ABL of the upper adjacent level (p < 0.05); and 0.0° in grade 0 and 1 ABL vs. 3.5° in grade 2 ABL of the lower adjacent level (p < 0.05). A female predominance of ABL was found. Hybrid surgery and artificial disc size were also related to ABL. Conclusions: ABL is more common in Baguera C Disc arthroplasty than Bryan Disc arthroplasty. Larger shell angle was related to ABL after CDA with Baguera C Discs, which may indicate that shell angle is pivotal in determining the incidence of ABL after CDA. Females had more ABL with Baguera C Disc arthroplasty; this might be related to shorter endplate lengths as well as a smaller endplate-implant mismatch.


Asunto(s)
Enfermedades Óseas Metabólicas , Degeneración del Disco Intervertebral , Disco Intervertebral , Reeemplazo Total de Disco , Humanos , Femenino , Masculino , Estudios Retrospectivos , Vértebras Cervicales/diagnóstico por imagen , Vértebras Cervicales/cirugía , Artroplastia/efectos adversos , Cuello/cirugía , Prótesis e Implantes , Resultado del Tratamiento , Degeneración del Disco Intervertebral/diagnóstico por imagen , Degeneración del Disco Intervertebral/cirugía , Rango del Movimiento Articular , Disco Intervertebral/diagnóstico por imagen , Disco Intervertebral/cirugía , Reeemplazo Total de Disco/efectos adversos
14.
Int J Rheum Dis ; 26(10): 1996-2006, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37565304

RESUMEN

AIM: An estimated 88% of rheumatoid arthritis (RA) patients experience various degrees of cervical spine involvement. The excessive movement of the atlantoaxial joint, which connects the occiput to the upper cervical spine, results in atlantoaxial instability (AAI). AAI stabilization is usually achieved by C1 lateral mass-to-C2 pedicle screw-rod fixation (LC1-PC2 fixation), which is technically challenging in RA patients who often show destructive changes in anatomical structures. This study aimed to analyze the clinical results and operative experiences of C1-C2 surgery, with emphasis on the advancement of image-guided surgery and augmented reality (AR) assisted navigation. METHODS: We presented our two decades of experience in the surgical management of AAI from April 2004 to November 2022. RESULTS: We have performed surgery on 67 patients with AAI, including 21 traumatic odontoid fractures, 20 degenerative osteoarthritis, 11 inflammatory diseases of RA, 5 congenital anomalies of the os odontoideum, 2 unknown etiologies, 2 movement disorders, 2 previous implant failures, 2 osteomyelitis, 1 ankylosing spondylitis, and 1 tumor. Beginning in 2007, we performed LC1-PC2 fixation under C-arm fluoroscopy. As part of the progress in spinal surgery, since 2011 we used surgical navigation from presurgical planning to intraoperative navigation, using the preoperative computed tomography (CT) -based image-guided BrainLab navigation system. In 2021, we began using intraoperative CT scan and microscope-based AR navigation. CONCLUSION: The technical complexities of C1-C2 surgery can be mitigated by CT-based image-guided surgery and microscope-based AR navigation, to improve accuracy in screw placement and overall clinical outcomes, particularly in RA patients with AAI.

15.
Parasit Vectors ; 14(1): 551, 2021 Oct 26.
Artículo en Inglés | MEDLINE | ID: mdl-34702321

RESUMEN

BACKGROUND: Mosquito-borne dengue virus (DENV) causes major disease worldwide, impacting 50-100 million people every year, and is spread by the major mosquito vector Aedes aegypti. Understanding mosquito physiology, including antiviral mechanisms, and developing new control strategies have become an important step towards the elimination of DENV disease. In the study reported here, we focused on autophagy, a pathway suggested as having a positive influence on virus replication in humans, as a potential antiviral target in the mosquito. METHODS: To understand the role played by autophagy in Ae. aegypti, we examined the activation of this pathway in Aag-2 cells, an Ae. aegypti-derived cell line, infected with DENV. Rapamycin and 3-methyladenine, two small molecules that have been shown to affect the function of the autophagy pathway, were used to activate or suppress, respectively, the autophagy pathway. RESULTS: At 1-day post-DENV infection in Aag-2 cells, transcript levels of both the microtubule-associated protein light chain 3-phosphatidylethanolamine conjugate (LC3-II) and autophagy-related protein 1 (ATG1) increased. Rapamycin treatment activated the autophagy pathway as early as 1-h post-treatment, and the virus titer had decreased in the Aag-2 cells at 2 days post-infection; in contrast, the 3-methyladenine treatment did not significantly affect the DENV titer. Treatment with these small molecules also impacted the ATG12 transcript levels in DENV-infected cells. CONCLUSIONS: Our studies revealed that activation of the autophagy pathway through rapamycin treatment altered DENV infection in the mosquito cells, suggesting that this pathway could be a possible antiviral mechanism in the mosquito system. Here we provide fundamental information needed to proceed with future experiments and to improve our understanding of the mosquito's immune response against DENV.


Asunto(s)
Aedes/virología , Autofagia/genética , Virus del Dengue/fisiología , Mosquitos Vectores/virología , Adenina/análogos & derivados , Adenina/farmacología , Aedes/citología , Aedes/genética , Animales , Autofagia/efectos de los fármacos , Línea Celular , Dengue/transmisión , Mosquitos Vectores/genética , Sirolimus/farmacología , Replicación Viral
16.
Insects ; 12(1)2021 Jan 14.
Artículo en Inglés | MEDLINE | ID: mdl-33466960

RESUMEN

Aedes aegypti, as one of the vectors transmitting several arboviruses, is the main target in mosquito control programs. Permethrin is used to control mosquitoes and Aedes aegypti get exposed due to its overuse and are now resistant. The increasing percentage of permethrin resistant Aedes aegypti has become an important issue around the world and the potential influence on vectorial capacity needs to be studied. Here we selected a permethrin resistant (p-s) Aedes aegypti population from a wild Florida population and confirmed the resistance ratio to its parental population. We used allele-specific PCR genotyping of the V1016I and F1534C sites in the sodium channel gene to map mutations responsible for the resistance. Two important factors, survival rate and vector competence, that impact vectorial capacity were checked. Results indicated the p-s population had 20 times more resistance to permethrin based on LD50 compared to the parental population. In the genotyping study, the p-s population had more homozygous mutations in both mutant sites of the sodium channel gene. The p-s adults survived longer and had a higher dissemination rate for dengue virus than the parental population. These results suggest that highly permethrin resistant Aedes aegypti populations might affect the vectorial capacity, moreover, resistance increased the survival time and vector competence, which should be of concern in areas where permethrin is applied.

17.
J Vis Exp ; (170)2021 04 15.
Artículo en Inglés | MEDLINE | ID: mdl-33938890

RESUMEN

A recently published DNA extraction protocol using magnetic beads and an automated DNA extraction instrument suggested that it is possible to extract high quality and quantity DNA from a well-preserved individual mosquito sufficient for downstream whole genome sequencing. However, reliance on an expensive automated DNA extraction instrument can be prohibitive for many laboratories. Here, the study provides a budget-friendly magnetic-bead-based DNA extraction protocol, which is suitable for low to medium throughput. The protocol described here was successfully tested using individual Aedes aegypti mosquito samples. The reduced costs associated with high quality DNA extraction will increase the application of high throughput sequencing to resource limited labs and studies.


Asunto(s)
Aedes/genética , ADN/aislamiento & purificación , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Análisis de Secuencia de ADN/métodos , Animales , Fenómenos Magnéticos
18.
J Int Med Res ; 49(1): 300060520986685, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33472475

RESUMEN

OBJECTIVE: Pediatric lumbar disc herniation (LDH), although uncommon, causes significant pain, discomfort, and sometimes disability. We examined the efficacy of percutaneous endoscopic lumbar discectomy (PELD) for pediatric LDH and the degree of lumbar disc degeneration at 1 year after PELD. METHODS: We retrospectively reviewed the data of pediatric patients with LDH who underwent PELD from December 2007 to July 2018. The patients' symptoms, physical examination findings, clinical images, visual analog scale (VAS) scores, Oswestry Disability Index (ODI), and perioperative results (blood loss, length of hospital stay, and complications) were obtained from the medical records. Lumbar disc degeneration was graded using the modified Pfirrmann grading system at the 1-year postoperative magnetic resonance imaging (MRI) examination. RESULTS: Six boys and four girls who underwent PELD were evaluated. The patients' mean age was 15.6 years (range, 13-17 years). The mean VAS score for low back pain, mean VAS score for lower limb pain, and mean ODI preoperatively and 1 year postoperatively were 6.2 and 0.3, 6.9 and 0.5, and 20 and 0.1, respectively. MRI showed significant disc degeneration after PELD. CONCLUSIONS: Treating pediatric LDH with PELD is safe and effective. It relieves pain and reduces disability. However, lumbar disc degeneration still occurs.


Asunto(s)
Discectomía Percutánea , Degeneración del Disco Intervertebral , Desplazamiento del Disco Intervertebral , Adolescente , Niño , Discectomía , Endoscopía , Femenino , Humanos , Degeneración del Disco Intervertebral/diagnóstico por imagen , Degeneración del Disco Intervertebral/cirugía , Desplazamiento del Disco Intervertebral/diagnóstico por imagen , Desplazamiento del Disco Intervertebral/cirugía , Vértebras Lumbares/diagnóstico por imagen , Vértebras Lumbares/cirugía , Imagen por Resonancia Magnética , Espectroscopía de Resonancia Magnética , Masculino , Estudios Retrospectivos , Resultado del Tratamiento
19.
J Chin Med Assoc ; 84(11): 1019-1022, 2021 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-34261980

RESUMEN

BACKGROUND: Dopamine agonists such as bromocriptine and cabergoline have been found to be an effective treatment for hyperprolactinemia, not only inducing adenoma shrinkage but also lowering serum prolactin levels. Among known dopamine agonists, cabergoline is the drug of choice due to its enhanced tolerability compared with bromocriptine. This study aimed to evaluate cabergoline's effectiveness, along with transsphenoidal surgery, in the treatment of hyperprolactinemia. METHODS: We retrieved all patients with a diagnosis of prolactinoma who were treated in our hospital during 2000-2018. A total of 208 patients were enrolled in the analysis after applying exclusion criteria. Patients were divided into four groups according to the treatments received. The demographic data, dosage and duration of cabergoline, and serum prolactin levels at different time points were collected for analysis. RESULTS: Normalization was achieved in 59 patients (83.10%) within a short median duration of 2.80 months among those treated with cabergoline only. Although cabergoline alone was effective and well-tolerated, our data showed that long-term remission rates were more favorable when surgery was involved. The long-term remission rate of all patients enrolled was 53.8% (112 patients among 208 patients). The long-term remission rates for the different treatment groups were 17.8% (8 of 45 patients) in Group 1 (Operation→Drug), 83.3% (5 of 6 patients) in Group 2 (Drug→Operation), 79.0% (68 of 86 patients) in Group 3 (Operation only), and 43.7% (31 of 71 patients) in Group 4 (Drug only). CONCLUSION: Cabergoline has been demonstrated to be effective and should be considered as a first-line treatment for hyperprolactinemia. In our study, transsphenoidal surgery was also demonstrated to achieve good results compared with medical treatment. Surgical intervention may resurface as an alternative first-line treatment. When used in combination with cabergoline, surgery offers a higher disease remission rate than either drug or operation alone.


Asunto(s)
Cabergolina/uso terapéutico , Agonistas de Dopamina/uso terapéutico , Hiperprolactinemia/tratamiento farmacológico , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad
20.
Pathogens ; 10(8)2021 Jul 28.
Artículo en Inglés | MEDLINE | ID: mdl-34451411

RESUMEN

Florida lies within a subtropical region where the climate allows diverse mosquito species including invasive species to thrive year-round. As of 2021, there are currently 66 state-approved Florida Mosquito Control Districts, which are major stakeholders for Florida public universities engaged in mosquito research. Florida is one of the few states with extensive organized mosquito control programs. The Florida State Government and Florida Mosquito Control Districts have long histories of collaboration with research institutions. During fall 2020, we carried out a survey to collect baseline data on the current control priorities from Florida Mosquito Control Districts relating to (1) priority control species, (2) common adult and larval control methods, and (3) major research questions to address that will improve their control and surveillance programs. The survey data showed that a total of 17 distinct mosquito species were considered to be priority control targets, with many of these species being understudied. The most common control approaches included truck-mounted ultra-low-volume adulticiding and biopesticide-based larviciding. The districts held interest in diverse research questions, with many prioritizing studies on basic science questions to help develop evidence-based control strategies. Our data highlight the fact that mosquito control approaches and priorities differ greatly between districts and provide an important point of comparison for other regions investing in mosquito control, particularly those with similar ecological settings, and great diversity of potential mosquito vectors, such as in Florida. Our findings highlight a need for greater alignment of research priorities between mosquito control and mosquito research. In particular, we note a need to prioritize filling knowledge gaps relating to understudied mosquito species that have been implicated in arbovirus transmission.

SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA