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1.
Pediatr Blood Cancer ; : e31082, 2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38804869

RESUMEN

INTRODUCTION: Children, adolescents, and young adults (CAYAs) with Down syndrome (DS) and hematologic malignancies are particularly vulnerable to infections and related complications. There are limited data regarding COVID-19 infections in this group. We aimed to understand the clinical course of COVID-19 in this population. METHODS: This observational study leverages the de-identified clinical and sociodemographic data captured by the Pediatric Oncology COVID-19 Case Report Registry (POCC) regarding CAYAs with cancer and COVID-19. We evaluated CAYAs (≤21 years at COVID-19 infection) with hematologic malignancies and COVID-19 reported from April 1, 2020 to May 2, 2023, comparing those with and without DS. Using multivariable logistic regression, we examined rates of hospitalization, intensive care unit (ICU) admission, respiratory support, and changes in cancer-directed therapy. RESULTS: Among 1408 CAYAs with hematologic malignancies, 55 had DS (CAYA-DS). CAYA-DS had higher rates of hospitalization, ICU admission, and respiratory support (p < .001) than CAYAs without DS. Similarly, multivariable analyses found higher odds of hospitalization (odds ratio [OR] = 2.8, 95% confidence interval [CI]: 1.5-5.1), ICU admission (OR = 4.2, 95% CI: 1.9-9.1), and need for respiratory support (OR = 4.2, 95% CI: 2.0-8.8) among CAYA-DS. Modifications to cancer-directed therapy were more common among CAYA-DS when related to neutropenia (p = .001), but not when unrelated to neutropenia (p = .88); CAYA-DS did not have higher odds of changes to cancer-directed therapy (OR = 1.20, 95% CI: 0.7-2.1). CONCLUSIONS: We identify CAYA-DS with hematologic malignancies as a vulnerable subpopulation at greater risk for severe COVID-19 infection. This can inform conversations with patients and families regarding therapeutic and preventive measures, as well as the risks and benefits of modifying chemotherapy in the setting of COVID-19.

2.
Artículo en Inglés | MEDLINE | ID: mdl-38791797

RESUMEN

BACKGROUND: Adolescent and young adult (AYA) survivors of childhood cancer are increasingly recognized as a vulnerable group with unique emotional, social, and practical needs due to the intersection of cancer survivorship and normal developmental processes. Mindfulness meditation has shown early efficacy in improving psychological distress among cancer patients. However, the overall scientific study of app-based mindfulness-based interventions is still in its early stages. The goal of this study was to evaluate the feasibility and acceptability of a commercially available mindfulness mobile app intervention "Ten Percent Happier" among AYA survivors of childhood cancer. METHODS: We conducted a single-arm pilot intervention with 25 AYA survivors of childhood cancer ages 18-29 years. RESULTS: A total of 108 potentially eligible individuals were initially identified for screening. Of the 45 individuals reached (contact rate = 41.67%), 20 declined to participate; 25 were enrolled in the study and completed the baseline survey (enrollment rate = 55.56%). Twenty-one participants completed the study (retention rate = 84%). Changes in several outcomes were promising, with medium to large effect sizes: Mindfulness (d = 0.74), Negative Emotion (d = 0.48), Perceived Stress (d = 0.52), and Mental Health (d = 0.45). Furthermore, results suggested that participants with consistent app usage showed greater improvement in reported outcomes than those who stopped their usage (e.g., Mindfulness: d = 0.74, Perceived Stress: d = 0.83, Mental Health: d = 0.51; Meaning and Purpose: d = 0.84; and Sleep Disturbance: d = 0.81). Qualitative feedback indicated high satisfaction, but participants suggested adding group or individual peer support to improve their experience with the app. CONCLUSIONS: AYA survivors can be difficult to reach, but a mindfulness app was feasible and acceptable to this group. In particular, the robust retention rate and high satisfaction ratings indicate that the meditation mobile app was well received. Preliminary results suggest positive changes in health-related quality of life outcomes, warranting a larger efficacy trial.


Asunto(s)
Supervivientes de Cáncer , Estudios de Factibilidad , Meditación , Atención Plena , Aplicaciones Móviles , Neoplasias , Humanos , Adolescente , Adulto Joven , Masculino , Femenino , Supervivientes de Cáncer/psicología , Adulto , Meditación/métodos , Atención Plena/métodos , Neoplasias/psicología , Neoplasias/terapia , Proyectos Piloto , Estrés Psicológico/terapia , Estrés Psicológico/psicología
3.
Metabolites ; 14(5)2024 May 18.
Artículo en Inglés | MEDLINE | ID: mdl-38786765

RESUMEN

South Asians (SAs) have a higher risk of developing type 2 diabetes (T2D) than white Europeans, especially following gestational diabetes mellitus (GDM). Despite similar blood glucose levels post-GDM, SAs exhibit more insulin resistance (IR) than Nordics, though the underlying mechanisms are unclear. This study aimed to assess markers of adipose tissue (AT) IR and liver fat in SA and Nordic women post-GDM. A total of 179 SA and 108 Nordic women in Norway underwent oral glucose tolerance tests 1-3 years post-GDM. We measured metabolic markers and calculated the AT IR index and non-alcoholic fatty liver disease liver fat (NAFLD-LFS) scores. Results showed that normoglycaemic SAs had less non-esterified fatty acid (NEFA) suppression during the test, resembling prediabetes/T2D responses, and higher levels of plasma fetuin-A, CRP, and IL-6 but lower adiponectin, indicating AT inflammation. Furthermore, normoglycaemic SAs had higher NAFLD-LFS scores, lower insulin clearance, and higher peripheral insulin than Nordics, indicating increased AT IR, inflammation, and liver fat in SAs. Higher liver fat markers significantly contributed to the ethnic disparities in glucose metabolism, suggesting a key area for intervention to reduce T2D risk post-GDM in SAs.

4.
Oncol Res ; 32(5): 877-897, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38686045

RESUMEN

Background: Glioblastoma multiforme (GBM) is recognized as the most lethal and most highly invasive tumor. The high likelihood of treatment failure arises from the presence of the blood-brain barrier (BBB) and stem cells around GBM, which avert the entry of chemotherapeutic drugs into the tumor mass. Objective: Recently, several researchers have designed novel nanocarrier systems like liposomes, dendrimers, metallic nanoparticles, nanodiamonds, and nanorobot approaches, allowing drugs to infiltrate the BBB more efficiently, opening up innovative avenues to prevail over therapy problems and radiation therapy. Methods: Relevant literature for this manuscript has been collected from a comprehensive and systematic search of databases, for example, PubMed, Science Direct, Google Scholar, and others, using specific keyword combinations, including "glioblastoma," "brain tumor," "nanocarriers," and several others. Conclusion: This review also provides deep insights into recent advancements in nanocarrier-based formulations and technologies for GBM management. Elucidation of various scientific advances in conjunction with encouraging findings concerning the future perspectives and challenges of nanocarriers for effective brain tumor management has also been discussed.


Asunto(s)
Barrera Hematoencefálica , Neoplasias Encefálicas , Portadores de Fármacos , Glioblastoma , Nanopartículas , Humanos , Barrera Hematoencefálica/metabolismo , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/metabolismo , Portadores de Fármacos/química , Glioblastoma/tratamiento farmacológico , Glioblastoma/patología , Glioblastoma/metabolismo , Nanopartículas/química , Antineoplásicos/administración & dosificación , Antineoplásicos/uso terapéutico , Sistemas de Liberación de Medicamentos/métodos , Animales
5.
Med Chem ; 2024 04 02.
Artículo en Inglés | MEDLINE | ID: mdl-38571348

RESUMEN

Viruses are acellular, microscopic, and mobile particles containing genetic particles, either DNA/RNA strands as nucleoproteins, responsible for 69,53,743 deaths till the year 2023. Curcumin and related compounds are among the areas of pivotal interest for researchers because of their versatile pharmacological profile. Chemically known as diferuloylmethane, which is a main constituent of turmeric along with demethoxycurcumin and bisdemethoxycurcumin, they have a broad spectrum of antiviral activity against viruses such as human immunodeficiency virus, herpes simplex virus, influenza virus (Avian influenza) and Hepatitis C virus HIV. The possible role of curcumin as an antiviral agent may be attributed to the activation of the 20S proteasome, a cellular machinery responsible for degrading unfolded or misfolded proteins in a ubiquitin-independent manner. It shows suppression of HBV entry at various infection stages by inhibiting cccDNA replication by inhibiting the Wnt/ß-catenin signaling pathway to attenuate IAV-induced myocarditis.

6.
J Natl Cancer Inst ; 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38627241

RESUMEN

Adolescents and Young Adults (AYAs: 15-39 y) with cancer face unique vulnerabilities, yet remain under-represented on clinical trials, including adult registries of COVID-19 in cancer (AYAs: 8-12%). Thus, we leveraged the Pediatric Oncology COVID-19 Case Report (POCC) to examine the clinical course of COVID-19 among AYAs with cancer. POCC collects de-identified clinical and sociodemographic data regarding 0-39yo with cancer (AYAs = 37%) and COVID-19 from >100 institutions. Between 04/01/2020-11/28/2023, 191 older AYAs [22-39y] and 640 younger AYAs [15-21y] were captured. Older AYAs were less often hospitalized (p < .001), admitted to the intensive care unit (ICU, p = .02), and/or required respiratory support (p = .057). In multivariable analyses, older AYAs faced 80% lower odds of ICU admission but 2.3-times greater odds of changes to cancer-directed therapy. Unvaccinated patients had 5.4-times higher odds of ICU admission. Among AYAs with cancer, the COVID-19 course varies by age. These findings can inform pediatric/adult oncology teams surrounding COVID-19 management and prevention.

7.
Plant Direct ; 8(3): e572, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38500675

RESUMEN

Extracellular matrix (ECM) plays central roles in cell architecture, innate defense and cell wall integrity (CWI) signaling. During transition to multicellularity, modular domain structures of ECM proteins and proteoforms have evolved due to continuous adaptation across taxonomic clades under different ecological niche. Although this incredible diversity has to some extent been investigated at protein level, extracellular phosphorylation events and molecular evolution of ECM proteoform families remains unexplored. We developed matrisome proteoform atlas in a grain legume, chickpea and performed meta-analyses of 74 plant matrisomes. MS/MS analysis identified 1,424 proteins and 315 phosphoproteins involved in diverse functions. Cross-species ECM protein network identified proteoforms associated with CWI maintenance system. Phylogenetic characterization of eighteen matrix protein families highlighted the role of taxon-specific paralogs and orthologs. Novel information was acquired on gene expansion and loss, co-divergence, sub functionalization and neofunctionalization during evolution. Modular networks of matrix protein families and hub proteins showed higher diversity across taxonomic clades than among organs. Furthermore, protein families differ in nonsynonymous to synonymous substitution rates. Our study pointed towards the matrix proteoform functionality, sequence divergence variation, interactions between wall remodelers and molecular evolution using a phylogenetic framework. This is the first report on comprehensive matrisome proteoform network illustrating presence of CWI signaling proteins in land plants.

8.
Public Health Nutr ; 27(1): e55, 2024 Feb 06.
Artículo en Inglés | MEDLINE | ID: mdl-38316533

RESUMEN

OBJECTIVE: Dietary assessment tools should be designed for the target population. We developed an FFQ designed to assess diet in South Asian women in Norway. The study objective was to evaluate this FFQ using 24-h dietary recalls as reference method. DESIGN: Approximately 3 weeks after the participants (n 40) had filled in the FFQ, the first of three non-consecutive 24-h dietary recalls was completed. The recalls were telephone-based, unannounced and performed by a trained dietitian, with 2-3 weeks between each interview. SETTING: The DIASA 1 study, in Oslo, Norway. PARTICIPANTS: Women of South Asian ethnic origin participating in the DIASA 1 study were invited to participate in the evaluation study. RESULTS: The WebFFQasia significantly overestimated the absolute intake of energy, protein, fat and carbohydrates compared with the 24-h dietary recalls. Absolute intakes of sugar, starch and fibre did not differ significantly between the methods. For energy percentages (E%), there were no significant differences, except for monounsaturated fat. Correlations were strong for E% from sugar and saturated fat and moderate for E% from fibre, carbohydrate, total fat and protein. Fourteen food groups out of twenty three were not significantly different compared with the reference method, and sixteen groups showed strong to moderate correlations. CONCLUSION: The WebFFQasia may be used to assess E% from habitual diet and can adequately estimate intakes and rank participants according to nutrient intake and main food categories at group level.


Asunto(s)
Dieta , Ingestión de Energía , Humanos , Femenino , Recuerdo Mental , Grasas de la Dieta , Noruega , Encuestas y Cuestionarios , Reproducibilidad de los Resultados , Encuestas sobre Dietas , Azúcares , Registros de Dieta
9.
Luminescence ; 39(1): e4679, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38286606

RESUMEN

In this work, (99 - x)CaSO4 -Dy2 O3 -xEu2 O3 , (where x = 0, 0.05, 0.1, 0.2, 0.3, 0.4, 0.5) thermoluminescence phosphors were prepared using a coprecipitation method. The thermoluminescence (TL) dosimetry (TLD) characteristics such as TL sensitivity, dose-response, minimum detectable dose, thermal fading, and the effect of sunlight on the prepared phosphors were investigated. The obtained results indicated that the most sensitive phosphor was obtained at x = 0.05. Large thermal fading of 6% after 1 h and 26% after 24 h from irradiation followed by 71% after 1 month with no additional fading was observed within a time frame exceeding 2 months throughout the remaining duration of the investigation, which also spanned over 2 months. Despite the phosphor's high fading rate, the relative sensitivity of the prepared samples was ~90% compared with TLD-100. The marked effect of day sunlight was also determined. High dose-response within the low-dose range from 0.01 to 5 Gy was observed. The obtained results suggested that the synthesized phosphor is well suited for applications involving radiation biology and radiotherapy dosimetry.


Asunto(s)
Disprosio , Dosimetría Termoluminiscente , Dosimetría Termoluminiscente/métodos
10.
Ir J Med Sci ; 193(2): 949-955, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37561387

RESUMEN

BACKGROUND AND AIMS: Early neurological deterioration (END) in acute ischemic stroke (AIS), patients is defined as clinical worsening or recurrence during first 72 h after onset of AIS. We have conducted this study to determine the association between END and functional outcome at 3 months of onset of AIS along with associated risk factors of END in AIS cases. METHODOLOGY: This study was conducted after approval of Institute Ethics Committee. Two hundred three consecutive patients were admitted from September 2020 to January 2022 at a tertiary care hospital. One hundred ninety patients were included in the study; patients were divided into two groups: (1) early neurological deterioration (END) and (2) non-early neurological deterioration (non-END). Patients were followed-up either telephonically or in person at approximately 3 months using modified Rankin Scale 0-6. All the clinically significant prognostic markers and p < 0.10 variables were considered significant in univariate analysis; P < 0.05 were considered statistically significant for the multivariate analysis. RESULTS: Out of 190 cases included in the cohort 34/190 (17.8%) cases showed END with mean age (56.56 (± 16.6)) and males (20/34 (58.8%)). END was independently associated with high blood glucose at admission (OR = 1.015; P = 0.002; 95%CI = 1.005-1.024) and low serum albumin (OR = 0.208; P = 0.002; 95%CI = 0.077-0.562). Patients with END showed poor functional outcome (mRS > 2) at end of 3 months (32 (94.1%); P < 0.001) and death was also statistically significant (22 (64.7%); P < 0.001) as compared to AIS cases having non-END. CONCLUSION: Our study showed END may be associated with poor functional outcome in AIS patients. Higher blood glucose at admission and low serum albumin may be statistically significant causing END. Future prospective cohort with larger sample size may confirm the findings.


Asunto(s)
Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Masculino , Humanos , Accidente Cerebrovascular/complicaciones , Glucemia , Hospitalización , Albúmina Sérica
11.
Saudi Pharm J ; 32(1): 101910, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38111669

RESUMEN

Ulcerative colitis (UC) is an inflammatory condition of colon characterized by severe damage to the innermost colon tissues. A number of studies described the use of medication delivery systems based on natural polymers like polysaccharides for the purpose of reaching the colon. In this research, polymer-based mesalamine delayed-release granules (DRGs) were tested for their antioxidant and anti-inflammatory efficacy against UC. Chitosan (C), pectin (P), and pectin-chitosan (PC) mesalamine (M) DRGs were prepared and characterized. Data revealed satisfactory compatibility, flow, packing properties, drug release pattern, and delayed drug release by DRGs. Wistar rats were treated with 2,4,6-trinitrobenzenesulfonic acid (TNBS) (100 mg/kg) via rectal administration. Mesalamine and mesalamine DRGs (50 mg/kg) were administered orally separately for 14 days. Biomarkers of oxidative stress, inflammation, hematological tests, colon profile, and histopathology were performed. The findings demonstrated the good efficacy of the polysaccharides in delivering mesalamine to colon. Mesalamine and mesalamine DRGs based on various polymers showed significant antioxidant and anti-inflammatory effects in rats with UC. Mesalamine granules significantly attenuated colon lipid peroxidation, nitrites, myeloperoxidase activity, and interleukin-1ß levels, and improved anti-oxidants (GSH, SOD). Data showed upregulation of Nrf2 activity by mesalamine granules with CM-DRGs showing maximum effect. Mesalamine and different polymer-based mesalamine DRGs significantly attenuated TNBS-induced decline in body weight, ulcer severity, and colon damage. CM-DRGs showed the most pronounced ameliorative effect on colon and hematology parameters via anti-oxidant and anti-inflammatory activities. Chitosan can be used as a carrier for oral colon delivery of mesalamine in DRG formulation for enhanced therapeutic efficacy in UC.

12.
Cureus ; 15(10): e47144, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38021883

RESUMEN

We present a 22-year-old female with transfusion-dependent anemia due to sickle cell disease (SCD) with lipopolysaccharide-responsive and beige-like anchor protein (LRBA) deficiency whose treatment frequency was moderated with voxelotor (Oxbryta®). The patient was transfusion dependent, initially thought to be secondary only to SCD. After the diagnosis of LRBA deficiency, her regimen included abatacept, sirolimus, hydroxyurea, and folic acid, but she still required intermittent transfusion. She was started on voxelotor in January 2020. Since initiation, her baseline hemoglobin level has increased and she is no longer transfusion dependent.

13.
Sci Rep ; 13(1): 16333, 2023 09 28.
Artículo en Inglés | MEDLINE | ID: mdl-37770496

RESUMEN

Lung adenocarcinoma (LUAD) is the most common malignant subtype of lung cancer (LC). miR-200 family is one of the prime miR regulators of epithelial-mesenchymal transition (EMT) and worst overall survival (OS) in LC patients. The study aimed to identify and validate the key differentially expressed immune-related genes (DEIRGs) regulated by miR-200 family which may serve for therapeutic aspects in LUAD tumor microenvironment (TME) by affecting cancer progression, invasion, and metastasis. The study identified differentially expressed miRNAs (DEMs) in LUAD, consisting of hsa-miR-200a-3p and hsa-miR-141-5p, respectively. Two highest-degree subnetwork motifs identified from 3-node miRNA FFL were: (i) miR-200a-3p-CX3CR1-SPIB and (ii) miR-141-5p-CXCR1-TBX21. TIMER analysis showed that the expression levels of CX3CR1 and CXCR1 were significantly positively correlated with infiltrating levels of M0-M2 macrophages and natural killer T (NKT) cells. The OS of LUAD patients was significantly affected by lower expression levels of hsa-miR-200a-3p, CX3CR1 and SPIB. These DEIRGs were validated using the human protein atlas (HPA) web server. Further, we validated the regulatory role of hsa-miR-200a-3p in an in-vitro indirect co-culture model using conditioned media from M0, M1 and M2 polarized macrophages (THP-1) and LUAD cell lines (A549 and H1299 cells). The results pointed out the essential role of hsa-miR-200a-3p regulated CX3CL1 and CX3CR1 expression in progression of LC TME. Thus, the study augments a comprehensive understanding and new strategies for LUAD treatment where miR-200 family regulated immune-related genes, especially chemokine receptors, which regulate the metastasis and invasion of LUAD, leading to the worst associated OS.


Asunto(s)
Adenocarcinoma del Pulmón , Adenocarcinoma , Neoplasias Pulmonares , MicroARNs , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/metabolismo , Adenocarcinoma del Pulmón/patología , MicroARNs/genética , MicroARNs/metabolismo , Adenocarcinoma/genética , Microambiente Tumoral/genética , Receptor 1 de Quimiocinas CX3C/genética
14.
Front Cell Infect Microbiol ; 13: 1125562, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37533933

RESUMEN

Introduction: Bovine mastitis is caused by over 150 different microorganisms. Specific identification and quantification of multiple bacteria in a single milk sample becomes essential for rapid intervention. Methods: In the present study a Luminex beads based multiplex assay emphasizing on the precise identification of six major bacterial pathogens of mastitis was developed. Assay was developed in two triplex sets, triplex 1 comprised of Streptococcus agalactiae, Streptococcus dysgalactiae and Streptococcus uberis while triplex 2 consisted of Staphylococcus aureus, E. coli and Klebsiella pneumoniae. Results: The analytical sensitivity was 10 6 copies per reaction mixture for all the six bacteria. A 100% analytical specificity was observed for simultaneous detection of these bacteria. Clinical milk samples from 100 bovine quarters were tested for validation. Discussion: The analytical sensitivity was similar to the findings reported earlier in real time PCR multiplex assay targeting the DNA of the 11 most common bacterial species or groups in mastitis. The analytical specificity of the optimized assay was 100% similar to reported earlier for simultaneous detection of Mycoplasma spp. and for seven entric viruses of humans.The developed assay indicates a concept proof of a rapid, cost effective high throughput diagnostic tool for identification of major bacteria causing mastitis.


Asunto(s)
Escherichia coli , Mastitis Bovina , Femenino , Humanos , Animales , Bovinos , Escherichia coli/genética , Leche , Bacterias/genética , Streptococcus agalactiae/genética , Mastitis Bovina/diagnóstico , Mastitis Bovina/microbiología
15.
J Appl Genet ; 64(4): 737-748, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37653284

RESUMEN

Lung cancer is one of the most commonly occurring malignant cancers with the highest rate of mortality globally. Difference between lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD) and their treatment strategies according to genetic markers may be helpful in reducing the cancer progression and increasing the overall survival (OS) in patients. LUSC is known for comparatively less typical onco-drivers, target therapy resistance, marked genomic complexity, and a reasonably higher mutation rate. The mRNA-seq data and clinical information of LUAD and LUSC cohorts from UCSC Xena comprising 437 and 379 patient samples were extracted. Differential expression and weighted network analyses revealed 47 and 18 hub differentially expressed genes (DEGs) corresponding to LUAD and LUSC cohorts. These hub DEGs were further subjected to protein-protein interaction network (PPIN) and OS analyses. Lower mRNA expression levels of both RPS15A and RPS7 worsened the OS of LUSC patients. Additionally, both these prognostic biomarkers were validated via external sources such as UALCAN, cBioPortal, TIMER, and HPA. RPS7 had higher mutation frequency compared to RPS15A and showed significant negative correlations with infiltrating levels of CD4+ T cells, CD8+ T cells, neutrophils, and macrophages. Our findings provided novel insights into biomarker discovery and the critical role of ribosomal biogenesis especially smaller ribosomal subunit in pathogenesis of LUSC.


Asunto(s)
Adenocarcinoma del Pulmón , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Humanos , Pronóstico , Multiómica , Linfocitos T CD8-positivos/metabolismo , Linfocitos T CD8-positivos/patología , Adenocarcinoma del Pulmón/genética , Neoplasias Pulmonares/genética , Carcinoma de Células Escamosas/genética , Pulmón/patología , ARN Mensajero/metabolismo
16.
Front Cell Neurosci ; 17: 1177663, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37388410

RESUMEN

The composition of the extracellular matrix (ECM) in nervous tissue plays an important role in controlling neuronal outgrowth and synapse development. Changes in both protein and glycosaminoglycan components of the ECM occur with tissue injury and may affect neuron growth. To investigate neuron responses to alterations in fibronectin (FN), a major component of the wound ECM, we grew cortical neurons on cell-derived decellularized matrices composed of wild type FN (FN+/+) or of a mutant form of FN (FNΔ/+) from which the III13 heparin-binding site had been deleted by CRISPR-Cas 9 gene editing. The most significant effect of the mutant FN was a reduction in dendrite outgrowth. Not only were dendrites shorter on mutant FNΔ/+-collagen (COL) matrix than on wild type (FN+/+-COL) matrix, but the number of dendrites and dendritic spines per neuron and the spine densities were also dramatically reduced on FNΔ/+-COL matrices. Mass spectrometry and immunostaining identified a reduction in tenascin-C (TN-C) levels in the mutant matrix. TN-C is an ECM protein that binds to the III13 site of FN and modulates cell-matrix interactions and has been linked to dendrite development. We propose that TN-C binding to FN in the wound matrix supports dendrite and spine development during repair of damaged neural tissue. Overall, these results show that changes in ECM composition can dramatically affect elaboration of neurites and support the idea that the ECM microenvironment controls neuron morphology and connectivity.

17.
Cancer Metastasis Rev ; 42(3): 847-889, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37204562

RESUMEN

Cancer is one of the life-threatening diseases accountable for millions of demises globally. The inadequate effectiveness of the existing chemotherapy and its harmful effects has resulted in the necessity of developing innovative anticancer agents. Thiazolidin-4-one scaffold is among the most important chemical skeletons that illustrate anticancer activity. Thiazolidin-4-one derivatives have been the subject of extensive research and current scientific literature reveals that these compounds have shown significant anticancer activities. This manuscript is an earnest attempt to review novel thiazolidin-4-one derivatives demonstrating considerable potential as anticancer agents along with a brief discussion of medicinal chemistry-related aspects of these compounds and structural activity relationship studies in order to develop possible multi-target enzyme inhibitors. Most recently, various synthetic strategies have been developed by researchers to get various thiazolidin-4-one derivatives. In this review, the authors highlight the various synthetic, green, and nanomaterial-based synthesis routes of thiazolidin-4-ones as well as their role in anticancer activity by inhibition of various enzymes and cell lines. The detailed description of the existing modern standards in the field presented in this article may be interesting and beneficial to the scientists for further exploration of these heterocyclic compounds as possible anticancer agents.


Asunto(s)
Antineoplásicos , Neoplasias , Humanos , Neoplasias/tratamiento farmacológico , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Antineoplásicos/química , Relación Estructura-Actividad
18.
JAMA Oncol ; 9(8): 1108-1112, 2023 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-37166782

RESUMEN

Importance: Little is known about the risk of post-COVID-19 multisystem inflammatory syndrome in children (MIS-C) in the setting of childhood cancer. Objective: To evaluate factors associated with MIS-C and describe the clinical course of COVID-19 in the setting of MIS-C. Design, Setting, and Participants: Multisite observational cohort study of a registry representing more than 100 US pediatric oncology sites. All included patients were registered between April 1, 2020, and May 18, 2022. Sites submitted deidentified data surrounding sociodemographics, cancer diagnosis and treatment, and COVID-19 course (symptoms, maximum support required, outcome). Patients with MIS-C (n = 24) were compared with matched controls (n = 96). Children (<21 years) with cancer who developed COVID-19 while receiving cancer treatment or within 1 year of completing treatment were characterized based on their development of MIS-C. Exposures: (1) Clinical and sociodemographic characteristics of children with cancer and COVID-19; and (2) MIS-C. Main Outcomes and Measures: (1) Development of MIS-C among children with cancer and COVID-19; and (2) symptoms and disease severity associated with MIS-C. Results: Among 2035 children with cancer and COVID-19, 24 (1.2%) developed MIS-C. COVID-19 occurred at a median (IQR) age of 12.5 (5.5-17.1) years in those with MIS-C and 11 (6-16) years among matched controls (P = .86). The majority of children with MIS-C had a hematologic cancer (83.3% [n = 20]), were publicly insured (66.7% [n = 16]), and were Hispanic (54.2% [n = 13]). Half (n = 12) had 1 or more noncancer comorbidity. Those with comorbidities were more likely to develop MIS-C than those without (odds ratio [OR], 2.5 [95% CI, 1.1-5.7]). Among children with MIS-C, 100% (n = 24) were admitted to the hospital and 54.2% (n = 13) to the intensive care unit (ICU), while COVID-19 contributed to the death of 20.1% (n = 5); cancer therapy was changed in 62.5% (n = 15). Compared with matched controls, those with MIS-C had higher odds of symptoms classified as systemic (OR, 4.7 [95% CI, 1.4-15.8]) or gastrointestinal (OR, 5.0 [95% CI, 1.7-14.6]) along with higher odds of hospitalization (OR, 42.9 [95% CI, 7.1-258]), ICU admission (OR, 11.4 [95% CI, 3.6-36.4]), and changes to cancer therapy (OR, 24.9 [95% CI, 6.5-94.8]). Conclusions and Relevance: In this cohort study among children with cancer and COVID-19, those with MIS-C had a more severe clinical course than those without MIS-C. The risk of MIS-C and its severity are important to consider as clinicians monitor patients with COVID-19. These findings can inform their conversations with families regarding COVID-19 risks and the benefits of prevention strategies that are pharmacologic (vaccination) and nonpharmacologic (masking), as well as treatment (antivirals, monoclonal antibodies).


Asunto(s)
COVID-19 , Neoplasias , Niño , Humanos , Adolescente , COVID-19/complicaciones , COVID-19/epidemiología , COVID-19/terapia , SARS-CoV-2 , Estudios de Cohortes , Factores de Riesgo , Neoplasias/epidemiología , Neoplasias/terapia , Progresión de la Enfermedad
19.
Ann Indian Acad Neurol ; 26(1): 10-16, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37034042

RESUMEN

Cerebral collateral circulation refers to the auxiliary vascular structures which compensate cerebral blood flow when it has been compromised due to stenosis or occlusion of the principal supplying arteries. They play a vital role in sustaining blood flow to the ischemic areas in acute, subacute or chronic phases of ischemic stroke or TIA. Good collateral circulation has shown protective effects towards a favorable functional outcome and a lower risk of recurrence of stroke. The benchmark mechanical thrombectomy trials utilized these collateral scoring methods to guide patient selection and prognosticate favorable outcome models. This shows a promising future of the collateral circulation for extending the time frame of the reperfusion therapies by optimally guiding patient selection and moving from a "time window" to a "tissue window."

20.
Microbiol Res ; 270: 127317, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-36805163

RESUMEN

Albugo candida, the causal organism of white rust, is an oomycete obligate pathogen infecting crops of Brassicaceae family occurred on aerial part, including vegetable and oilseed crops at all growth stages. The disease expression is characterized by local infection appearing on the abaxial region developing white or creamy yellow blister (sori) on leaves and systemic infections cause hypertrophy and hyperplasia leading to stag-head of reproductive organ. To overcome this problem, several disease management strategies like fungicide treatments were used in the field and disease-resistant varieties have also been developed using conventional and molecular breeding. Due to high variability among A. candida isolates, there is no single approach available to understand the diverse spectrum of disease symptoms. In absence of resistance sources against pathogen, repetitive cultivation of genetically-similar varieties locally tends to attract oomycete pathogen causing heavy yield losses. In the present review, a deep insight into the underlying role of the non-host resistance (NHR) defence mechanism available in plants, and the strategies to exploit available gene pools from plant species that are non-host to A. candida could serve as novel sources of resistance. This work summaries the current knowledge pertaining to the resistance sources available in non-host germ plasm, the understanding of defence mechanisms and the advance strategies covers molecular, biochemical and nature-based solutions in protecting Brassica crops from white rust disease.


Asunto(s)
Brassica , Oomicetos , Brassica/genética , Hojas de la Planta , Oomicetos/genética , Enfermedades de las Plantas/genética , Resistencia a la Enfermedad
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