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1.
Dev Dyn ; 2024 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-39096180

RESUMO

BACKGROUND: Conjunctival placodes are a series of placodes that develop into the conjunctival (scleral) papillae and ultimately induce a series of scleral ossicles in the eyes of many vertebrates. This study establishes a hydrocortisone injection procedure (incl. dosage) that consistently inhibits all conjunctival papillae in the embryonic chicken eye. The effects of this hydrocortisone treatment on apoptosis, vasculature, and placode-related gene expression were assessed. RESULTS: Hydrocortisone treatment does not increase apoptotic cell death or have a major effect on the ciliary artery or vascular plexus in the eye. ß-catenin and Eda expression levels were not significantly altered following hydrocortisone treatment, despite the absence of conjunctival papillae. Notably, Fgf20 expression was significantly reduced following hydrocortisone treatment, and the distribution of ß-catenin was altered. CONCLUSIONS: Our study showed that conjunctival papillae induction begins as early as HH27.5 (E5.5). Hydrocortisone treatment reduces Fgf20 expression independently of ß-catenin and Eda and may instead affect other members of the Wnt/ß-catenin or Eda/Edar pathways, or it may affect the ability of morphogens to diffuse through the extracellular matrix. This study contributes to a growing profile of gene expression data during placode development and enhances our understanding of how some vertebrate eyes develop these fascinating bones.

2.
J Women Aging ; : 1-13, 2024 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-39097832

RESUMO

Although working men and women share common retirement concerns, women encounter unique challenges in securing their retirement. These challenges arise from factors such as part-time work, intermittent work histories, and potential wealth disparities. Marital status also exerts a profound influence on retirement decisions. Marital status significantly impacts their financial security as they approach retirement. This study investigates the intricate relationship between gender, marital status, and theory of planned behavior factors that influence retirement planning among older adults. Utilizing data from the 2014 Health and Retirement Study (HRS) and RAND, the research analyzed 2,657 participants aged 50 to 62, all of whom reported full or part-time employment. Also, the research leveraged the theory of planned behavior to examine motivational factors affecting retirement planning. The study's findings highlight the significant association of gender with expected retirement timing, revealing that married women typically anticipate retiring earlier than both unmarried women and men. In addition, older adults who secure retirement resources tend to retire earlier. It is important to develop tailored policies and initiatives to address the specific retirement challenges women face. It is imperative to develop retirement support systems that consider the gender, marital statuses, and retirement resources of older adults, and to give special attention to those who are vulnerable. This study provides valuable insights into the intricate interplay of gender, marital status, retirement motivation factors and retirement planning among older adults.

3.
Front Pharmacol ; 15: 1401599, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39050757

RESUMO

With over 450 genes, solute carriers (SLCs) constitute the largest transporter superfamily responsible for the uptake and efflux of nutrients, metabolites, and xenobiotics in human cells. SLCs are associated with a wide variety of human diseases, including cancer, diabetes, and metabolic and neurological disorders. They represent an important therapeutic target class that remains only partly exploited as therapeutics that target SLCs are scarce. Additionally, many small molecules reported in the literature to target SLCs are poorly characterized. Both features may be due to the difficulty of developing SLC transport assays that fulfill the quality criteria for high-throughput screening. Here, we report one of the main limitations hampering assay development within the RESOLUTE consortium: the lack of a resource providing high-quality information on SLC tool compounds. To address this, we provide a systematic annotation of tool compounds targeting SLCs. We first provide an overview on RESOLUTE assays. Next, we present a list of SLC-targeting compounds collected from the literature and public databases; we found that most data sources lacked specificity data. Finally, we report on experimental tests of 19 selected compounds against a panel of 13 SLCs from seven different families. Except for a few inhibitors, which were active on unrelated SLCs, the tested inhibitors demonstrated high selectivity for their reported targets. To make this knowledge easily accessible to the scientific community, we created an interactive dashboard displaying the collected data in the RESOLUTE web portal (https://re-solute.eu). We anticipate that our open-access resources on assays and compounds will support the development of future drug discovery campaigns for SLCs.

4.
Ann Fam Med ; 22(4): 350-351, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39038974
6.
Artigo em Inglês | MEDLINE | ID: mdl-38923387

RESUMO

INTRODUCTION: The intersection between perinatal mental health and the coronavirus disease 2019 (COVID-19) pandemic remains of significant public health importance. The current study examined the emotional and financial well-being and predictors of elevated depressive symptoms among pregnant women during the COVID-19 pandemic. METHODS: This online survey was conducted with 2118 women ≥18 years old who were pregnant at the time of the survey and living in the United States or Puerto Rico. Depressive symptoms were assessed with the Center for Epidemiologic Studies Depression Scale, with scores ≥10 indicative of elevated depressive symptoms. The final logistic regression model included housing insecurity, financial distress, COVID-19 diagnosis, exposure to COVID-19, and demographic covariates. RESULTS: More than half the sample (53.8%) had elevated depressive symptoms. In logistic regression analyses, the odds of having elevated depressive symptoms were significantly higher for participants reporting housing insecurity (adjusted odds ratio [aOR], 1.56; 95% CI, 1.22-2.01), financial distress (aOR, 1.57; 95% CI, 1.17-2.12), COVID-19 diagnosis (aOR, 2.53; 95% CI, 1.53-4.17), and COVID-19 exposure (aOR, 1.41; 95% CI, 1.07-1.86), after adjusting for covariates. The association of elevated depressive symptoms with housing insecurity was especially strong among those who experienced COVID-19 (aOR, 6.04; 95% CI, 2.15-17.0). DISCUSSION: Our findings are consistent with previous literature revealing that diagnosis, exposure, concerns about family, and effects on financial stability were related to depressive symptoms during the pandemic. The relationships between financial and housing concerns with elevated depressive symptoms, independent of concerns about infection in family members, suggest that there may be direct and indirect effects of the pandemic on mental health.

7.
Front Endocrinol (Lausanne) ; 15: 1365738, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38836231

RESUMO

Hypertension, a multifaceted cardiovascular disorder influenced by genetic, epigenetic, and environmental factors, poses a significant risk for the development of coronary artery disease (CAD) in individuals with type 2 diabetes mellitus (T2DM). Epigenetic alterations, particularly in histone modifications, DNA methylation, and microRNAs, play a pivotal role in unraveling the complex molecular underpinnings of blood pressure regulation. This review emphasizes the crucial interplay between epigenetic attributes and hypertension, shedding light on the prominence of DNA methylation, both globally and at the gene-specific level, in essential hypertension. Additionally, histone modifications, including acetylation and methylation, emerge as essential epigenetic markers linked to hypertension. Furthermore, microRNAs exert regulatory influence on blood pressure homeostasis, targeting key genes within the aldosterone and renin-angiotensin pathways. Understanding the intricate crosstalk between genetics and epigenetics in hypertension is particularly pertinent in the context of its interaction with T2DM, where hypertension serves as a notable risk factor for the development of CAD. These findings not only contribute to the comprehensive elucidation of essential hypertension but also offer promising avenues for innovative strategies in the prevention and treatment of cardiovascular complications, especially in the context of T2DM.


Assuntos
Doença da Artéria Coronariana , Diabetes Mellitus Tipo 2 , Epigênese Genética , Hipertensão , Humanos , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/complicações , Doença da Artéria Coronariana/genética , Doença da Artéria Coronariana/etiologia , Hipertensão/genética , Hipertensão/complicações , Fatores de Risco , Metilação de DNA , MicroRNAs/genética , Animais
8.
Cancer Lett ; 596: 217001, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38838764

RESUMO

Older patients have similar immune checkpoint inhibitor efficacy and rates of adverse events as younger patients, but appear to have decreased tolerability, particularly in the oldest patient cohort (>80 years), often leading to early cessation of therapy. We aimed to determine whether early discontinuation impacts efficacy of anti-PD-1 therapy in patients ≥80 years old. In this retrospective, multicenter, international cohort study, we examined 773 patients with 4 tumor types who were at least 80 years old and treated with anti-PD-1 therapy. We determined response rate, overall survival (OS), and progression-free survival (PFS) in patients who discontinued therapy early (<12 months) for reasons other than progression or death. We used descriptive statistics for demographics, response, and toxicity rates. Survival statistics were described using Kaplan Meier curves. Median (range) age at anti-PD-1 initiation was 83.0 (75.8-97.0) years. The cancer types included were melanoma (n = 286), non-small cell lung cancer (NSCLC) (n = 345), urothelial cell carcinoma (UCC) (n = 108), and renal cell carcinoma (RCC) (n = 34). Of these, 102 met the primary endpoint of <12 months to discontinuation for reasons other than death or progression. Median PFS and OS, respectively, for these patients were 34.4 months and 46.6 months for melanoma, 15.8 months and 23.4 months for NSCLC, and 10.4 months and 15.8 months for UCC. This study suggests geriatric patients who have demonstrated therapeutic benefit and discontinued anti-PD-1 therapy at less than 12 months of duration for reasons other than progression may have durable clinical benefit without additional therapy.


Assuntos
Inibidores de Checkpoint Imunológico , Humanos , Estudos Retrospectivos , Feminino , Masculino , Idoso de 80 Anos ou mais , Inibidores de Checkpoint Imunológico/efeitos adversos , Inibidores de Checkpoint Imunológico/uso terapêutico , Idoso , Intervalo Livre de Progressão , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Neoplasias/tratamento farmacológico , Neoplasias/mortalidade , Neoplasias/imunologia , Melanoma/tratamento farmacológico , Melanoma/mortalidade , Melanoma/imunologia , Melanoma/patologia , Resultado do Tratamento , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/imunologia , Suspensão de Tratamento/estatística & dados numéricos , Fatores de Tempo , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/imunologia , Carcinoma de Células Renais/patologia
9.
Front Pharmacol ; 15: 1372109, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38783936

RESUMO

The prostaglandin transporter (PGT, SLCO2A1) mediates transport of prostanoids (a.o. prostaglandin E2 (PGE2)) into cells and thereby promotes their degradation. Overexpression of PGT leads to low extracellular PGE2 levels and has been linked to impaired wound healing of diabetic foot ulcers. Inhibition of PGT could thus be beneficial, however, no PGT inhibitors are currently on the market and drug discovery efforts are hampered by lack of high-through screening assays for this transporter. Here we report on a label-free impedance-based assay for PGT that measures transport activity through receptor activation (TRACT) utilizing prostaglandin E2 receptor subtype EP3 and EP4 that are activated by PGE2. We found that induction of PGT expression on HEK293-JumpIn-SLCO2A1 cells that also express EP3 and EP4 leads to an over 10-fold reduction in agonistic potency of PGE2. PGE2 potency could be recovered upon inhibition of PGT-mediated PGE2 uptake with PGT inhibitors olmesartan and T26A, the potency of which could be established as well. Moreover, the TRACT assay enabled the assessment of transport function of PGT natural variants. Lastly, HUVEC cells endogenously expressing prostanoid receptors and PGT were exploited to study wound healing properties of PGE2 and T26A in real-time using a novel impedance-based scratch-induced wound healing assay. These novel impedance-based assays will advance PGT drug discovery efforts and pave the way for the development of PGT-based therapies.

10.
Front Oncol ; 14: 1395978, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38812776

RESUMO

Background: In the era of immune checkpoint blockade, the role of cancer vaccines in immune priming has provided additional potential for therapeutic improvements. Prior studies have demonstrated delayed type hypersensitivity and anti-tumor immunity with vaccines engineered to secrete granulocyte-macrophage colony-stimulating factor (GM-CSF). The safety, efficacy and anti-tumor immunity of GM-CSF secreting vaccine in patients with previously treated stage III or IV melanoma needs further investigation. Methods: In this phase II trial, excised lymph node metastases were processed to single cells, transduced with an adenoviral vector encoding GM-CSF, irradiated, and cryopreserved. Individual vaccines were composed of 1x106, 4x106, or 1x107 tumor cells, and were injected intradermally and subcutaneously at weekly and biweekly intervals. The primary endpoints were feasibility of producing vaccine in stage III patients and determining the proportion of patients alive at two years in stage IV patients. Results: GM-CSF vaccine was successfully developed and administered in all 61 patients. Toxicities were restricted to grade 1-2 local skin reactions. The median OS for stage III patients (n = 20) was 71.1 (95% CI, 43.7 to NR) months and 14.9 (95%CI, 12.1 to 39.7) months for stage IV patients. The median PFS in stage III patients was 50.7 (95%CI, 36.3 to NR) months and 4.1 (95% CI, 3.0-6.3) months in stage IV patients. In the overall population, the disease control rate was 39.3% (95%CI, 27.1 to 52.7%). In stage III patients, higher pre-treatment plasma cytokine levels of MMP-1, TRAIL, CXCL-11, CXCL-13 were associated with improved PFS (p<0.05 for all). An increase in post-vaccination levels of IL-15 and TRAIL for stage III patients was associated with improved PFS (p=0.03 for both). Similarly, an increase in post-vaccination IL-16 level for stage IV patients was associated with improved PFS (p=0.02) and clinical benefit. Conclusions: Vaccination with autologous melanoma cells secreting GM-CSF augments antitumor immunity in stage III and IV patients with melanoma, is safe, and demonstrates disease control. Luminex data suggests that changes in inflammatory cytokines and immune cell infiltration promote tumor antigen presentation and subsequent tumor cell destruction. Additional investigation to administer this vaccine in combination with immune checkpoint inhibitors is needed.

11.
J Insect Sci ; 24(2)2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38569059

RESUMO

Declines in bumble bee species range and abundances are documented across multiple continents and have prompted the need for research to aid species recovery and conservation. The rusty patched bumble bee (Bombus affinis) is the first federally listed bumble bee species in North America. We conducted a range-wide population genetics study of B. affinis from across all extant conservation units to inform conservation efforts. To understand the species' vulnerability and help establish recovery targets, we examined population structure, patterns of genetic diversity, and population differentiation. Additionally, we conducted a site-level analysis of colony abundance to inform prioritizing areas for conservation, translocation, and other recovery actions. We find substantial evidence of population structuring along an east-to-west gradient. Putative populations show evidence of isolation by distance, high inbreeding coefficients, and a range-wide male diploidy rate of ~15%. Our results suggest the Appalachians represent a genetically distinct cluster with high levels of private alleles and substantial differentiation from the rest of the extant range. Site-level analyses suggest low colony abundance estimates for B. affinis compared to similar datasets of stable, co-occurring species. These results lend genetic support to trends from observational studies, suggesting that B. affinis has undergone a recent decline and exhibit substantial spatial structure. The low colony abundances observed here suggest caution in overinterpreting the stability of populations even where B. affinis is reliably detected interannually. These results help delineate informed management units, provide context for the potential risks of translocation programs, and help set clear recovery targets for this and other threatened bumble bee species.


Assuntos
Himenópteros , Abelhas/genética , Masculino , Animais , Espécies em Perigo de Extinção
12.
Zebrafish ; 21(2): 92-100, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38621209

RESUMO

Zebrafish have been used as an education tool for students of all ages and can be used in many learning environments to teach different fields of science. In this study, we focus on the biology of zebrafish. We describe an educational program within a weeklong science camp for students between 12 and 14 years old. The methodology described is based on running annual science camps over an 11-year period. In these camps, students learnt about the developmental stages of zebrafish, as well as general zebrafish biology, husbandry, ecology, behavior, and reproduction. This article describes how to provide students and educators with an educational program to explore, discover, and contribute to the ever-evolving landscape of biological understanding through active and visual learning. We describe the methodology, the evaluation, revisions to our program over time, and future directions for expansion.


Assuntos
Estudantes , Peixe-Zebra , Animais , Humanos , Pesquisa , Aprendizagem Espacial , Ensino
14.
Innov Aging ; 8(4): igad141, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38628821

RESUMO

Background and Objectives: Prior research has highlighted the beneficial impact of social networks and social support on older adults' physical and psychosocial well-being. However, the impact of the relationship between chronic illness and social networks on the psychosocial well-being of older Nigerians remains understudied. This study explored how older Nigerians with chronic illnesses navigate the physical, mental, and emotional changes due to their chronic disease diagnosis within their social contexts. Research Design and Methods: The current qualitative study used semistructured in-depth interviews with 19 purposively sampled older adults, aged 50 years and over, chronically ill, and receiving clinical care to examine the role of social networks in how chronically ill older Nigerians cope with their diagnosis. Results: Three main themes reflecting participants' experiences emerged from the findings: (1) closely knit circles, (2) privacy and self-sufficiency, and (3) body image. Results show that chronically ill older Nigerians prefer to keep the knowledge of their conditions strictly within their close family circles. It was considered horrific to inform friends, community members, and religious groups about one's chronic illness. Findings further reveal that the need to appear healthy to one's social network stems from the fear of being discriminated against and attempts to maintain some level of normalcy when interacting with others. Additionally, feelings of inferiority and shame limited their participation in social activities and social network maintenance. Discussion and Implications: We discuss the implications of the results for the mental well-being and quality of life of chronically ill older Nigerians and make recommendations for policies and resources that can improve the well-being of chronically ill Nigerians.

15.
Life Sci Space Res (Amst) ; 41: 127-135, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38670639

RESUMO

Understanding how skeletal tissues respond to microgravity is ever more important with the increased interest in human space travel. Here, we exposed larval Danio rerio at 3.5 dpf to simulated microgravity (SMG) using a 3D mode of rotation in a ground-based experiment and then studied different cellular, molecular, and morphological bone responses both immediately after exposure and one week later. Our results indicate an overall decrease in ossification in several developing skeletal elements immediately after SMG exposure with the exception of the otoliths, however ossification returns to normal levels seven days after exposure. Coincident with the reduction in overall ossification tnfsf11 (RANKL) expression is highly elevated after 24 h of SMG exposure and also returns to normal levels seven days after exposure. We also show that genes associated with osteoblasts are unaffected immediately after SMG exposure. Thus, the observed reduction in ossification is primarily the result of a high level of bone resorption. This study sheds insight into the nuances of how osteoblasts and osteoclasts in the skeleton of a vertebrate organism respond to an external environmental disturbance, in this case simulated microgravity.


Assuntos
Larva , Osteogênese , Simulação de Ausência de Peso , Peixe-Zebra , Animais , Larva/crescimento & desenvolvimento , Larva/fisiologia , Osteoblastos/fisiologia , Osteoclastos/fisiologia , Ligante RANK/metabolismo , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo , Ausência de Peso/efeitos adversos
16.
Biomed Res Int ; 2024: 6761451, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38659608

RESUMO

This bibliometric analysis explores the landscape of research on the associations between specific genotypes and the cardiovascular form of diabetic neuropathy. Diabetes mellitus (DM) is a major contributor to premature mortality, primarily due to increased susceptibility to cardiovascular diseases. The global prevalence of DM is rising, with projections indicating further increases. Diabetic neuropathy, a complication of DM, includes the cardiovascular subtype, posing challenges in diagnosis and management. Understanding the genetic basis of cardiovascular diabetic neuropathy is crucial for targeted therapeutic interventions. The study utilizes bibliometric analysis to synthesize existing literature, identify trends, and guide future research. The Scopus database was searched, applying inclusion criteria for English articles related to genotypes and cardiovascular diabetic neuropathy. The analysis reveals a dynamic field with a notable impact, collaborative efforts, and multidimensional aspects. Publication trends over 1997-2023 demonstrate fluctuating research intensity. Top journals, authors, and affiliations are highlighted, emphasizing global contributions. Keyword analysis reveals thematic trends, and citation analysis identifies influential documents. Limitations include database biases, incomplete metadata, and search query specificity. The urgent need to explore genetic factors in cardiovascular diabetic neuropathy aligns with the increasing global diabetes burden. This analysis provides a comprehensive overview, contributing to the broader discourse on diabetic neuropathy research.


Assuntos
Bibliometria , Doenças Cardiovasculares , Neuropatias Diabéticas , Genótipo , Humanos , Neuropatias Diabéticas/genética , Neuropatias Diabéticas/epidemiologia , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/epidemiologia , Predisposição Genética para Doença
17.
ACS Chem Neurosci ; 15(7): 1424-1431, 2024 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-38478848

RESUMO

Excitatory amino acid transporters (EAATs) are important regulators of amino acid transport and in particular glutamate. Recently, more interest has arisen in these transporters in the context of neurodegenerative diseases. This calls for ways to modulate these targets to drive glutamate transport, EAAT2 and EAAT3 in particular. Several inhibitors (competitive and noncompetitive) exist to block glutamate transport; however, activators remain scarce. Recently, GT949 was proposed as a selective activator of EAAT2, as tested in a radioligand uptake assay. In the presented research, we aimed to validate the use of GT949 to activate EAAT2-driven glutamate transport by applying an innovative, impedance-based, whole-cell assay (xCELLigence). A broad range of GT949 concentrations in a variety of cellular environments were tested in this assay. As expected, no activation of EAAT3 could be detected. Yet, surprisingly, no biological activation of GT949 on EAAT2 could be observed in this assay either. To validate whether the impedance-based assay was not suited to pick up increased glutamate uptake or if the compound might not induce activation in this setup, we performed radioligand uptake assays. Two setups were utilized; a novel method compared to previously published research, and in a reproducible fashion copying the methods used in the existing literature. Nonetheless, activation of neither EAAT2 nor EAAT3 could be observed in these assays. Furthermore, no evidence of GT949 binding or stabilization of purified EAAT2 could be observed in a thermal shift assay. To conclude, based on experimental evidence in the present study GT949 requires specific assay conditions, which are difficult to reproduce, and the compound cannot simply be classified as an activator of EAAT2 based on the presented evidence. Hence, further research is required to develop the tools needed to identify new EAAT modulators and use their potential as a therapeutic target.


Assuntos
Transportador 2 de Aminoácido Excitatório , Ácido Glutâmico , Transportador 2 de Aminoácido Excitatório/metabolismo , Impedância Elétrica , Ácido Glutâmico/metabolismo , Transporte Biológico , Transportador 3 de Aminoácido Excitatório/metabolismo
18.
Foods ; 13(5)2024 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-38472805

RESUMO

A fruit leather (apple and acáchul berry) oriented toward women of reproductive age was developed. The snack was supplemented with an ingredient composed of folic acid (FA) and whey proteins (WPI) to ensure the required vitamin intake to prevent fetal neural tube defects. In order to generate a low-calorie snack, alternative sweeteners were used (stevia and maltitol). The fruit leather composition was determined. Also, an in vitro digestion process was carried out to evaluate the bioaccessibility of compounds with antioxidant capacity (AC), total polyphenols (TPCs), total monomeric anthocyanins (ACY), and FA. The quantification of FA was conducted by a microbiological method and by HPLC. The leather contained carbohydrates (70%) and antioxidant compounds, mainly from fruits. Bioaccessibility was high for AC (50%) and TPCs (90%), and low for ACY (17%). Regarding FA, bioaccessibility was higher for WPI-FA (50%) than for FA alone (37%), suggesting that WPI effectively protected the vitamin from processing and digestion. Furthermore, the product was shown to be non-cytotoxic in a Caco-2 cell model. The developed snack is an interesting option due to its low energy intake, no added sugar, and high content of bioactive compounds. Also, the supplementation with WPI-FA improved the conservation and bioaccessibility of FA.

19.
Front Microbiol ; 15: 1378989, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38544863

RESUMO

Nature utilizes three distinct pathways to synthesize the essential enzyme cofactor heme. The coproporphyrin III-dependent pathway, predominantly present in Bacillaceae, employs an oxygen-dependent coproporphyrinogen III oxidase (CgoX) that converts coproporphyrinogen III into coproporphyrin III. In this study, we report the bioinformatic-based identification of a gene called ytpQ, encoding a putative oxygen-independent counterpart, which we propose to term CgoN, from Priestia (Bacillus) megaterium. The recombinantly produced, purified, and monomeric YtpQ (CgoN) protein is shown to catalyze the oxygen-independent conversion of coproporphyrinogen III into coproporphyrin III. Minimal non-enzymatic conversion of coproporphyrinogen III was observed under the anaerobic test conditions employed in this study. FAD was identified as a cofactor, and menadione served as an artificial acceptor for the six abstracted electrons, with a KM value of 3.95 µmol/L and a kcat of 0.63 per min for the substrate. The resulting coproporphyrin III, in turn, acts as an effective substrate for the subsequent enzyme of the pathway, the coproporphyrin III ferrochelatase (CpfC). Under aerobic conditions, oxygen directly serves as an electron acceptor, but is replaced by the more efficient action of menadione. An AlphaFold2 model of the enzyme suggests that YtpQ adopts a compact triangular shape consisting of three domains. The N-terminal domain appears to be flexible with respect to the rest of the structure, potentially creating a ligand binding site that opens and closes during the catalytic cycle. A catalytic mechanism similar to the oxygen-independent protoporphyrinogen IX oxidase PgoH1 (HemG), based on the flavin-dependent abstraction of six electrons from coproporphyrinogen III and their potential quinone-dependent transfer to a membrane-localized electron transport chain, is proposed.

20.
Ophthalmol Retina ; 8(8): 823-831, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38447921

RESUMO

OBJECTIVE: To evaluate clinical characteristics impacting surgical outcomes of patients undergoing pars plana vitrectomy (PPV) for complications of proliferative diabetic retinopathy (PDR). DESIGN: Retrospective consecutive observational case series of patients at a large county hospital in Dallas, Texas, from 2014 to 2019. SUBJECTS: Seven hundred thirty-two patients (933 eyes) undergoing PPV for PDR complications. METHODS: Collected data included demographics, surgical indication, adjuvant therapies, intraoperative course, complications, and best corrected visual acuity (BCVA). Patients with < 6 months of follow-up were excluded. Best corrected visual acuity was converted to logarithm of the minimum angle of resolution for analysis. Statistics performed included t test, analysis of variance, and multivariate analyses. MAIN OUTCOME MEASURES: Postoperative BCVA, primary anatomic success rate, and postoperative complications. RESULTS: Three hundred ninety-three patients were male (509 eyes; 54.5%) with an average age of 52 years. Postoperative BCVA at 6 months was significantly different among surgical indications: 0.79 versus 0.77 versus 1.20 (P < 0.0001) for vitreous hemorrhage (VH), vitreomacular interface abnormalities, and tractional retinal detachment (TRD), respectively. Adjuvant preoperative therapy with panretinal photocoagulation (PRP) versus no PRP (0.95 vs. 1.25; P < 0.001) and insulin versus no insulin (0.99 vs. 1.17; P < 0.01) were associated with improved vision. Iatrogenic breaks were associated with decreased postoperative vision (1.40 vs. 0.88; P < 0.001). The primary anatomic success rate for TRD was 85% (495 eyes). Combined TRD/RRD (tractional and rhegmatogenous retinal detachment) was associated with a lower success rate compared with macula-on/macula-off TRD, with odds ratios of 0.36, 0.46, and 0.53, respectively. Patients experiencing recurrent detachment postsurgery had worse preoperative visual acuity (VA) (1.93 vs. 1.63; P < 0.01) and were younger (47.6 vs. 50.0; P = 0.02). Postoperative complications occurred in 699 eyes (75%), with VH (498 eyes, 53%), cataract (465, 50%), and elevated intraocular pressure (149, 16%) being the most common. Two hundred thirty-six eyes (25%) required a second PPV operation. Endophthalmitis (1 eye; <1%) and choroidal detachment (5 eyes; <1%) were rare. CONCLUSIONS: In this retrospective series analyzing surgical outcomes among patients with complications from PDR, vitrectomy led to improved vision on average, with a meaningful proportion of patients receiving additional surgical intervention. Surgical indication, presenting VA, age, and adjuvant therapies appeared to impact outcomes. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.


Assuntos
Retinopatia Diabética , Acuidade Visual , Vitrectomia , Humanos , Vitrectomia/métodos , Masculino , Estudos Retrospectivos , Feminino , Pessoa de Meia-Idade , Retinopatia Diabética/cirurgia , Retinopatia Diabética/diagnóstico , Retinopatia Diabética/complicações , Seguimentos , Resultado do Tratamento , Idoso , Adulto , Complicações Pós-Operatórias , Tomografia de Coerência Óptica/métodos
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