Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 340
Filtrar
1.
J Fish Biol ; 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38711300

RESUMO

The present drainage network of Bulgaria is the result of a complex Neogene and Quaternary evolution. Karst, which has developed on 23% of the territory, further complicates the hydrological pattern. Fresh waters of Bulgaria drain into the Black Sea and the Aegean Sea basins and can be roughly divided into the Danube (Middle and Lower Danube), non-Danube Black Sea, East Aegean, and West Aegean hydrological regions. Phoxinus, a small leuciscid fish, has a mosaic distribution in all four of these regions, inhabiting small mountainous and semi-mountainous streams. Based on morphology, it was identified as three species, Phoxinus phoxinus in the Danube, Phoxinus strandjae in the non-Danube, and Phoxinus strymonicus in West Aegean region. Later, molecular data revealed Phoxinus csikii and Phoxinus lumaireul in the Middle Danube and P. csikii in the Lower Danube. Phoxinus has been the focus of many studies, showing a high molecular and morphological diversity, which is not entirely consistent with previous morphology-only-based taxonomic concepts. In this study, molecular (a mitochondrial marker and a nuclear marker) and morphological data from both historical and recently sampled collections were analysed to assess the applicability of the integrative approach in Phoxinus. The results showed a significant influence of the complex paleo- and recent hydrology on the currently observed genetic structure of the considered populations and species. Furthermore, the study also demonstrated a strong influence of phenotypic plasticity on the morphological analysis of Phoxinus and the lack of a clear differentiation between P. csikii and P. strandjae. A barcoded specimen was designated as neotype to fix the species named P. strandjae in the current taxonomic concept. Finally, a significant discordance between genetically delimited clades and phenotypic groups did not allow a proper delineation of the species distributed in Bulgaria, demonstrating that more molecular markers are needed for further taxonomic study of the Phoxinus complex.

2.
Skin Res Technol ; 30(5): e13690, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38716749

RESUMO

BACKGROUND: The response of AI in situations that mimic real life scenarios is poorly explored in populations of high diversity. OBJECTIVE: To assess the accuracy and validate the relevance of an automated, algorithm-based analysis geared toward facial attributes devoted to the adornment routines of women. METHODS: In a cross-sectional study, two diversified groups presenting similar distributions such as age, ancestry, skin phototype, and geographical location was created from the selfie images of 1041 female in a US population. 521 images were analyzed as part of a new training dataset aimed to improve the original algorithm and 520 were aimed to validate the performance of the AI. From a total 23 facial attributes (16 continuous and 7 categorical), all images were analyzed by 24 make-up experts and by the automated descriptor tool. RESULTS: For all facial attributes, the new and the original automated tool both surpassed the grading of the experts on a diverse population of women. For the 16 continuous attributes, the gradings obtained by the new system strongly correlated with the assessment made by make-up experts (r ≥ 0.80; p < 0.0001) and supported by a low error rate. For the seven categorical attributes, the overall accuracy of the AI-facial descriptor was improved via enrichment of the training dataset. However, some weaker performance in spotting specific facial attributes were noted. CONCLUSION: In conclusion, the AI-automatic facial descriptor tool was deemed accurate for analysis of facial attributes for diverse women although some skin complexion, eye color, and hair features required some further finetuning.


Assuntos
Algoritmos , Face , Humanos , Feminino , Estudos Transversais , Adulto , Face/anatomia & histologia , Face/diagnóstico por imagem , Estados Unidos , Pessoa de Meia-Idade , Adulto Jovem , Fotografação , Reprodutibilidade dos Testes , Inteligência Artificial , Adolescente , Idoso , Pigmentação da Pele/fisiologia
3.
Wiad Lek ; 77(3): 506-513, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38691793

RESUMO

OBJECTIVE: Aim: To study and analyze the attitude of women of reproductive age to the integrated gynecological care provision by family physicians, their readiness to receive some gynecological services from family physicians, as well as to analyze the level of women's support and readiness for the integrated provision of gynecological care depending on age and level of education. PATIENTS AND METHODS: Materials and Methods: For the survey, anonymous questionnaires containing questions on the attitude of women of reproductive age to the integrated provision of certain types of gynecological care by family physicians were developed. 181 women from the Kyiv region took part in the survey. RESULTS: Results: Support of more than 80% of respondents regarding the integrated gynecological care provision by family physicians received the following questions: counseling on the prevention of sexually transmitted infections and human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) (92,3%); counseling on family planning and prevention of unwanted pregnancy (83,4%); counseling on the use of various methods of contraception (82,3%); examination and palpation of mammary glands (80,1%); referral of women to a higher level of obstetric and gynecological care (if necessary (86,2%). CONCLUSION: Conclusions: The majority of respondents (67,4%) are ready or better ready than not ready to receive certain types of gynecological care services from family physicians. Almost the same percentage ratio (more than 60%) of women of each age group and all levels of education are ready or better ready than not ready to receive gynecological care services, which they supported, from family physicians.


Assuntos
Ginecologia , Humanos , Feminino , Adulto , Ginecologia/estatística & dados numéricos , Inquéritos e Questionários , Adulto Jovem , Ucrânia , Pessoa de Meia-Idade , Médicos de Família/estatística & dados numéricos , Médicos de Família/psicologia , Prestação Integrada de Cuidados de Saúde , Medicina de Família e Comunidade , Adolescente
4.
Chemosphere ; : 142301, 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38740337

RESUMO

Bioplastics are considered sustainable alternatives to conventional microplastics which are recognized as a threat to terrestrial ecosystems. However, little is known about the potential ecotoxicological effects of bioplastics on soil fauna and ecosystems. The present study assessed the toxicity of microplastics [Polystyrene (PS), Polyethylene (PE)] and bioplastics [Polyvinyl alcohol (PVA), Sodium polyacrylate (NaPa) on a key soil fauna Oppia nitens, a soil oribatid mite, and investigated the ecological relevance of O. nitens avoidance response as a valuable tool for the risk assessment of contaminated soils such as the Superfund sites. Findings showed that the mites' net response indicated avoidance behavior such that in most cases as concentrations of micro- and bioplastics increased, so did the avoidance responses. The avoidance EC50 endpoints showed PS < PE < PVA < NaPa, indicating higher deleterious effects of microplastics. High toxicity of PS in soils to O. nitens at EC50 of 165 (± 25) mg/kg compared to bioplastics and other known contaminants poses an enormous threat to soil. For bioplastics in this study, there were no significant avoidances at concentrations up to 16,200 mg/kg compared to PS and PE which showed avoidance responses at 300 and 9,000 mg/kg respectively, implying that bioplastics might be relatively safer to soil mites compared to conventional microplastics. Also, results indicated that long term heavy metal pollution such as in contaminated Superfund sites decreased microbial biomass; a useful bioindicator of soil pollution. Furthermore, O. nitens avoidance of heavy metals contaminated sites demonstrated the ecological relevance of avoidance response test when assessing the habitat integrity of contaminated soil. The present study further supports the inclusion of the oribatid mite, O. nitens in the ecological risk assessment of contaminants in soil.

5.
Neurophotonics ; 11(2): 024209, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38725801

RESUMO

Significance: Pain comprises a complex interaction between motor action and somatosensation that is dependent on dynamic interactions between the brain and spinal cord. This makes understanding pain particularly challenging as it involves rich interactions between many circuits (e.g., neural and vascular) and signaling cascades throughout the body. As such, experimentation on a single region may lead to an incomplete and potentially incorrect understanding of crucial underlying mechanisms. Aim: We aimed to develop and validate tools to enable detailed and extended observation of neural and vascular activity in the brain and spinal cord. The first key set of innovations was targeted to developing novel imaging hardware that addresses the many challenges of multisite imaging. The second key set of innovations was targeted to enabling bioluminescent (BL) imaging, as this approach can address limitations of fluorescent microscopy including photobleaching, phototoxicity, and decreased resolution due to scattering of excitation signals. Approach: We designed 3D-printed brain and spinal cord implants to enable effective surgical implantations and optical access with wearable miniscopes or an open window (e.g., for one- or two-photon microscopy or optogenetic stimulation). We also tested the viability for BL imaging and developed a novel modified miniscope optimized for these signals (BLmini). Results: We describe "universal" implants for acute and chronic simultaneous brain-spinal cord imaging and optical stimulation. We further describe successful imaging of BL signals in both foci and a new miniscope, the "BLmini," which has reduced weight, cost, and form-factor relative to standard wearable miniscopes. Conclusions: The combination of 3D-printed implants, advanced imaging tools, and bioluminescence imaging techniques offers a coalition of methods for understanding spinal cord-brain interactions. Our work has the potential for use in future research into neuropathic pain and other sensory disorders and motor behavior.

6.
Am J Biol Anthropol ; : e24930, 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38581359

RESUMO

OBJECTIVES: Mildred Trotter was an anatomist and physical anthropologist whose studies on hair morphology, growth, somatic distribution, and trait relationships to age and ethnogeographic population were foundational to the field of microscopical hair analysis. The collection of human hair samples she assembled for her research has been an underutilized resource for studies on human hair variation. We applied updated methods and reviewed Trotter's original data to reassess the relationship hair traits have to diverse population labels. METHODS: Hair form and pigmentation patterns were measured from a subset of the hair samples accumulated by Trotter and we compared our data to Trotter's original results. Variability in hair traits were tested within individuals, within populations, and among ethnogeographic groups. RESULTS: Measured hair cross-section dimensions and melanosome density and distribution revealed substantial variability within individuals and ethnogeographic populations. Hair traits were found to not be distinctly separable by ancestry but instead showed continuous variation across human populations. Trotter's measurements were precise and the dataset she compiled remains valid, though the conclusions should be reviewed in light of our current understanding of human variation. DISCUSSION: Our findings support moving away from categorical ancestry classifications and eliminating the use of outdated racial typologies in favor of more descriptive trait analysis. Detailed analysis of trait pattern distributions are presented that may be useful for future research on human variation. We point to the need for additional research on human variation and hair trait relationships with reference to known population affinity.

7.
Biomol NMR Assign ; 18(1): 79-84, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38564159

RESUMO

The lipocalin protein family is a structurally conserved group of proteins with a variety of biological functions defined by their ability to bind small molecule ligands and interact with partner proteins. One member of this family is siderocalin, a protein found in mammals. Its role is discussed in inflammatory processes, iron trafficking, protection against bacterial infections and oxidative stress, cell migration, induction of apoptosis, and cancer. Though it seems to be involved in numerous essential pathways, the exact mechanisms are often not fully understood. The NMR backbone assignments for the human siderocalin and its rat ortholog have been published before. In this work we describe the backbone NMR assignments of siderocalin for another important model organism, the mouse - data that might become important for structure-based drug discovery. Secondary structure elements were predicted based on the assigned backbone chemical shifts using TALOS-N and CSI 3.0, revealing a high content of beta strands and one prominent alpha helical region. Our findings correlate well with the known crystal structure and the overall conserved fold of the lipocalin family.


Assuntos
Lipocalinas , Ressonância Magnética Nuclear Biomolecular , Estrutura Secundária de Proteína , Animais , Camundongos , Sequência de Aminoácidos , Lipocalina-2/química , Lipocalinas/química
9.
Artigo em Inglês | MEDLINE | ID: mdl-38433524

RESUMO

INTRODUCTION: Hyperpigmentation disorders are very frequent, affect the quality of life and may become a psychological burden for afflicted patients. Many anti-pigmenting or depigmenting agents are available with various efficacy and almost no comparative data. 2-mercaptonicotinoyl glycine (2-MNG) was recently proposed as a viable candidate showing safe and effective results on hyperpigmentation control in vitro and in vivo. OBJECTIVES: A Bayesian network meta-analysis (BNMA) was conducted to map and rank the anti-pigmenting and depigmenting efficacy of 2-MNG 0.5% on UV daylight (UVDL)-induced pigmentation together with 13 other reference molecules. A comparison in the kinetics of 2-MNG 0.5% was also performed. METHODOLOGY: Fourteen studies were conducted, for each, on 15-30 women of skin phototype III in Shanghai, China and Paris, France. The products were applied on mini zone, in randomized and blinded protocol, on the back, 5 days a week during 6 weeks, at a dose of 4 mg/cm2 . During the second week, volunteers were exposed under to varying minimum erythemal dose of UVDL during 4 consecutive days-adapted to obtain a similar induction of skin pigmentation regardless of the population. Assessments were performed instrumentally using Chromameter®. Ascorbic acid 7% was used as a positive control for all experiments. A Bayesian network meta-analysis was then established to map and follow the kinetics of 2-MNG 0.5% performance with 13 reference molecules (glutathione 2%, kojic acid 1%, hydroquinone 4%, ascorbyl glucoside 2%, niacinamide 4%, etc.). RESULTS: 2-MNG 0.5% dominated the ranking at all time points with a significant high probability of strong efficacy against UVDL-induced pigmentation. Ascorbic acid 7% ranks second after 4 days of irradiations (D12 ) whereas hydroquinone 4% ranks second 1 month after irradiations (D40 ). In the kinetics, 2-MNG at 0.5% was effective as from the end of irradiations (D12 ) to the study endpoint (D40 ). This suggested an immediate and persistent efficacy across all timepoints evaluated. CONCLUSION: The BNMA revealed a rapid and lasting efficacy of 2-MNG 0.5% on the anti-pigmenting and depigmenting phases of the clinical protocol. 2-MNG 0.5% ranked first, with immediate and lasting effect compared to 13 other references. This study is the first allowing comparison between reference anti-pigmenting and depigmenting agents and will help clinicians for proposing the most effective approach for their patients.

10.
Proc Natl Acad Sci U S A ; 121(14): e2304897121, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38547061

RESUMO

While the existence and functional role of class C G-protein-coupled receptors (GPCR) dimers is well established, there is still a lack of consensus regarding class A and B GPCR multimerization. This lack of consensus is largely due to the inherent challenges of demonstrating the presence of multimeric receptor complexes in a physiologically relevant cellular context. The C-X-C motif chemokine receptor 4 (CXCR4) is a class A GPCR that is a promising target of anticancer therapy. Here, we investigated the potential of CXCR4 to form multimeric complexes with other GPCRs and characterized the relative size of the complexes in a live-cell environment. Using a bimolecular fluorescence complementation (BiFC) assay, we identified the ß2 adrenergic receptor (ß2AR) as an interaction partner. To investigate the molecular scale details of CXCR4-ß2AR interactions, we used a time-resolved fluorescence spectroscopy method called pulsed-interleaved excitation fluorescence cross-correlation spectroscopy (PIE-FCCS). PIE-FCCS can resolve membrane protein density, diffusion, and multimerization state in live cells at physiological expression levels. We probed CXCR4 and ß2AR homo- and heteromultimerization in model cell lines and found that CXCR4 assembles into multimeric complexes larger than dimers in MDA-MB-231 human breast cancer cells and in HCC4006 human lung cancer cells. We also found that ß2AR associates with CXCR4 multimers in MDA-MB-231 and HCC4006 cells to a higher degree than in COS-7 and CHO cells and in a ligand-dependent manner. These results suggest that CXCR4-ß2AR heteromers are present in human cancer cells and that GPCR multimerization is significantly affected by the plasma membrane environment.


Assuntos
Neoplasias , Receptores Adrenérgicos beta 2 , Receptores CXCR4 , Transdução de Sinais , Animais , Cricetinae , Humanos , Células CHO , Cricetulus , Proteínas de Membrana/metabolismo , Neoplasias/metabolismo , Receptores CXCR4/metabolismo , Receptores Adrenérgicos beta 2/metabolismo , Multimerização Proteica
11.
Vaccines (Basel) ; 12(2)2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38400187

RESUMO

Within the past few decades, improvement in sanitation and economic growth has driven a changing epidemiology of hepatitis A in the Western Pacific Region (WPR) of the World Health Organization (WHO). In this review, we gathered available published information on hepatitis A epidemiology of the countries in the WPR and reviewed the trends reported in the literature from the years 2000 to 2021. Many countries have shifted from high endemicity to low endemicity. Moreover, the administration of the hepatitis A vaccine among children in recent years has shifted disease susceptibility to the older population. Seroprevalence among children has decreased in most countries, while nearly 100% seropositivity is seen in mid adulthood. This is contrary to the epidemiology seen in previous decades when most children achieved immunity by age ten. This also presents a paradox in that better living conditions have caused more vulnerability to the older age groups who are at higher risk for severe disease. Given these trends, we recommend vaccination of vulnerable populations such as the older age groups and inclusion of the hepatitis A vaccine in government immunization programs.

12.
One Earth ; 7(2): 325-335, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38420618

RESUMO

Short-term exposure to ground-level ozone in cities is associated with increased mortality and is expected to worsen with climate and emission changes. However, no study has yet comprehensively assessed future ozone-related acute mortality across diverse geographic areas, various climate scenarios, and using CMIP6 multi-model ensembles, limiting our knowledge on future changes in global ozone-related acute mortality and our ability to design targeted health policies. Here, we combine CMIP6 simulations and epidemiological data from 406 cities in 20 countries or regions. We find that ozone-related deaths in 406 cities will increase by 45 to 6,200 deaths/year between 2010 and 2014 and between 2050 and 2054, with attributable fractions increasing in all climate scenarios (from 0.17% to 0.22% total deaths), except the single scenario consistent with the Paris Climate Agreement (declines from 0.17% to 0.15% total deaths). These findings stress the need for more stringent air quality regulations, as current standards in many countries are inadequate.

13.
bioRxiv ; 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38405804

RESUMO

Pancreatic ductal adenocarcinoma (PDA) is partly initiated through the transdifferentiation of acinar cells to metaplastic ducts that act as precursors of neoplasia and cancer. Tuft cells are solitary chemosensory cells not found in the normal pancreas but arise in metaplasia and neoplasia, diminishing as neoplastic lesions progress to carcinoma. Metaplastic tuft cells (mTCs) function to suppress tumor progression through communication with the tumor microenvironment, but their fate during progression is unknown. To determine the fate of mTCs during PDA progression, we have created a lineage tracing model that uses a tamoxifen-inducible tuft-cell specific Pou2f3CreERT/+ driver to induce transgene expression, including the lineage tracer tdTomato or the oncogene Myc. mTC lineage trace models of pancreatic neoplasia and carcinoma were used to follow mTC fate. We found that mTCs, in the carcinoma model, transdifferentiate into neural-like progenitor cells (NRPs), a cell type associated with poor survival in PDA patients. Using conditional knock-out and overexpression systems, we found that Myc activity in mTCs is necessary and sufficient to induce this Tuft-to-Neuroendocrine-Transition (TNT).

14.
Alzheimers Res Ther ; 16(1): 20, 2024 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-38273408

RESUMO

BACKGROUND: Effective, disease-modifying therapeutics for the treatment of Alzheimer's disease (AD) remain a large unmet need. Extensive evidence suggests that amyloid beta (Aß) is central to AD pathophysiology, and Aß oligomers are among the most toxic forms of Aß. CT1812 is a novel brain penetrant sigma-2 receptor ligand that interferes with the binding of Aß oligomers to neurons. Preclinical studies of CT1812 have demonstrated its ability to displace Aß oligomers from neurons, restore synapses in cell cultures, and improve cognitive measures in mouse models of AD. CT1812 was found to be generally safe and well tolerated in a placebo-controlled phase 1 clinical trial in healthy volunteers and phase 1a/2 clinical trials in patients with mild to moderate dementia due to AD. The unique objective of this study was to incorporate synaptic positron emission tomography (PET) imaging as an outcome measure for CT1812 in AD patients. METHODS: The present phase 1/2 study was a randomized, double-blind, placebo-controlled, parallel-group trial conducted in 23 participants with mild to moderate dementia due to AD to primarily evaluate the safety of CT1812 and secondarily its pharmacodynamic effects. Participants received either placebo or 100 mg or 300 mg per day of oral CT1812 for 24 weeks. Pharmacodynamic effects were assessed using the exploratory efficacy endpoints synaptic vesicle glycoprotein 2A (SV2A) PET, fluorodeoxyglucose (FDG) PET, volumetric MRI, cognitive clinical measures, as well as cerebrospinal fluid (CSF) biomarkers of AD pathology and synaptic degeneration. RESULTS: No treatment differences relative to placebo were observed in the change from baseline at 24 weeks in either SV2A or FDG PET signal, the cognitive clinical rating scales, or in CSF biomarkers. Composite region volumetric MRI revealed a trend towards tissue preservation in participants treated with either dose of CT1812, and nominally significant differences with both doses of CT1812 compared to placebo were found in the pericentral, prefrontal, and hippocampal cortices. CT1812 was safe and well tolerated. CONCLUSIONS: The safety findings of this 24-week study and the observed changes on volumetric MRI with CT1812 support its further clinical development. TRIAL REGISTRATION: The clinical trial described in this manuscript is registered at clinicaltrials.gov (NCT03493282).


Assuntos
Doença de Alzheimer , Camundongos , Animais , Humanos , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Projetos Piloto , Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons , Biomarcadores/líquido cefalorraquidiano
15.
Plants (Basel) ; 13(2)2024 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-38276771

RESUMO

This study includes an assessment of the VIR (Center N.I. Vavilov All-Russian Institute of Plant Genetic Resources) chufa collection, grown in various ecological and geographical conditions of the Russian Federation: "Yekaterininskaya experimental station VIR" in the Tambov region and "Kuban experimental station VIR" in the Krasnodar Region during the years 2020-2021. The main indicators of the economic value of chufa accessions were studied: yield structure and nutritional value (oil, protein, starch, and fatty acid profile). The accessions were grown in regions with different climatic conditions. As a result of the study, the variability of the biochemical and yield characteristics and the correlation between the studied indicators and the factor structure of its variability were established. Of the 20 accessions used in the study, the accessions with the highest protein, starch, oil and unsaturated fatty acid contents were selected, which are the most promising for their use as a raw material to expand the range of regional functional food products, as well as for future breeding efforts in the development of new, promising regional chufa varieties.

16.
bioRxiv ; 2024 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-38168289

RESUMO

Cellular plasticity is a hallmark of pancreatic ductal adenocarcinoma (PDAC) starting from the conversion of normal cells into precancerous lesions to the progression of carcinoma subtypes associated with aggressiveness and therapeutic response. We discovered that normal acinar cell differentiation, maintained by the transcription factor Pdx1, suppresses a broad gastric cell identity that is maintained in metaplasia, neoplasia, and the classical subtype of PDAC in mouse and human. We have identified the receptor tyrosine kinase Ror2 as marker of a gastric metaplasia (SPEM)-like identity in the pancreas. Ablation of Ror2 in a mouse model of pancreatic tumorigenesis promoted a switch to a gastric pit cell identity that largely persisted through progression to the classical subtype of PDAC. In both human and mouse pancreatic cancer, ROR2 activity continued to antagonize the gastric pit cell identity, strongly promoting an epithelial to mesenchymal transition, conferring resistance to KRAS inhibition, and vulnerability to AKT inhibition.

17.
Mol Cancer Res ; 22(3): 295-307, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38015750

RESUMO

Idiopathic pulmonary fibrosis (IPF) is characterized by progressive, often fatal loss of lung function due to overactive collagen production and tissue scarring. Patients with IPF have a sevenfold-increased risk of developing lung cancer. The COVID-19 pandemic has increased the number of patients with lung diseases, and infection can worsen prognoses for those with chronic lung diseases and disease-associated cancer. Understanding the molecular pathogenesis of IPF-associated lung cancer is imperative for identifying diagnostic biomarkers and targeted therapies that will facilitate prevention of IPF and progression to lung cancer. To understand how IPF-associated fibroblast activation, matrix remodeling, epithelial-to-mesenchymal transition (EMT), and immune modulation influences lung cancer predisposition, we developed a mouse model to recapitulate the molecular pathogenesis of pulmonary fibrosis-associated lung cancer using the bleomycin and Lewis lung carcinoma models. We demonstrate that development of pulmonary fibrosis-associated lung cancer is likely linked to increased abundance of tumor-associated macrophages and a unique gene signature that supports an immune-suppressive microenvironment through secreted factors. Not surprisingly, preexisting fibrosis provides a pre-metastatic niche and results in augmented tumor growth, and tumors associated with bleomycin-induced fibrosis are characterized by a dramatic loss of cytokeratin expression, indicative of EMT. IMPLICATIONS: This characterization of tumors associated with lung diseases provides new therapeutic targets that may aid in the development of treatment paradigms for lung cancer patients with preexisting pulmonary diseases.


Assuntos
COVID-19 , Fibrose Pulmonar Idiopática , Neoplasias Pulmonares , Humanos , Animais , Camundongos , Neoplasias Pulmonares/genética , Pandemias , Fibrose Pulmonar Idiopática/genética , Bleomicina/toxicidade , Microambiente Tumoral
18.
Cancer Immunol Res ; 12(1): 91-106, 2024 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-37931247

RESUMO

Pancreatic ductal adenocarcinoma (PDA) continues to have a dismal prognosis. The poor survival of patients with PDA has been attributed to a high rate of early metastasis and low efficacy of current therapies, which partly result from its complex immunosuppressive tumor microenvironment. Previous studies from our group and others have shown that tumor-associated macrophages (TAM) are instrumental in maintaining immunosuppression in PDA. Here, we explored the role of Notch signaling, a key regulator of immune response, within the PDA microenvironment. We identified Notch pathway components in multiple immune cell types within human and mouse pancreatic cancer. TAMs, the most abundant immune cell population in the tumor microenvironment, expressed high levels of Notch receptors, with cognate ligands such as JAG1 expressed on tumor epithelial cells, endothelial cells, and fibroblasts. TAMs with activated Notch signaling expressed higher levels of immunosuppressive mediators, suggesting that Notch signaling plays a role in macrophage polarization within the PDA microenvironment. Genetic inhibition of Notch in myeloid cells led to reduced tumor size and decreased macrophage infiltration in an orthotopic PDA model. Combination of pharmacologic Notch inhibition with PD-1 blockade resulted in increased cytotoxic T-cell infiltration, tumor cell apoptosis, and smaller tumor size. Our work implicates macrophage Notch signaling in the establishment of immunosuppression and indicates that targeting the Notch pathway may improve the efficacy of immune-based therapies in patients with PDA.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Camundongos , Animais , Macrófagos Associados a Tumor/metabolismo , Células Endoteliais/metabolismo , Transdução de Sinais , Microambiente Tumoral
19.
Foods ; 12(24)2023 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-38137267

RESUMO

Consumption of fried foods is associated with a higher risk of cardiovascular and other diseases; therefore, consumers are looking to reduce fat intake. We evaluated the effect of high-protein breaders and fiber on oil absorption and quality attributes in chicken nuggets, using flour blends (wheat, chickpea, coconut, oil-quinoa-chia), soy protein concentrate, and brewers' spent grain. We evaluated the chemical composition, water and oil retention capacity (ORC), viscosity profile, and flour particle size distribution, along with the developed breaders (Formulation 1 and 2) and a commercial breader (CB), in addition to texture, color, fat, and moisture contents of the fried chicken nuggets prepared with the developed breaders and the CB. The total dietary fiber content (TDF) of the nuggets breaded with only Formulation-1 and CB was determined. Nuggets breaded with Formulation-1 showed lower (p ≤ 0.05) ORC, better moisture retention (67.6%), and more TDF (4.5% vs. 2.3%, p ≤ 0.05) compared to CB-breaded nuggets. Nuggets with Formulation-1 showed the expected texture and color characteristics for fried products. Formulation-1 has the potential to be used as a breader due to its moisture, reduced ORC, and the texture and color it imparts to the fried nuggets, providing higher amounts of nutrients and possible health benefits.

20.
Med Sci (Basel) ; 11(4)2023 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-38132917

RESUMO

Neisseria meningitidis (N. meningitidis) serogroup B (MenB) is the leading cause of invasive meningococcal disease worldwide. The pathogen has a wide range of virulence factors, which are potential vaccine components. Studying the genetic variability of antigens within a population, especially their long-term persistence, is necessary to develop new vaccines and predict the effectiveness of existing ones. The multicomponent 4CMenB vaccine (Bexsero), used since 2014, contains three major genome-derived recombinant proteins: factor H-binding protein (fHbp), Neisserial Heparin-Binding Antigen (NHBA) and Neisserial adhesin A (NadA). Here, we assessed the prevalence and sequence variations of these vaccine antigens in a panel of 5667 meningococcal isolates collected worldwide over the past 10 years and deposited in the PubMLST database. Using multiple amino acid sequence alignments and Random Forest Classifier machine learning methods, we estimated the potential strain coverage of fHbp and NHBA vaccine variants (51 and about 25%, respectively); the NadA antigen sequence was found in only 18% of MenB genomes analyzed, but cross-reactive variants were present in less than 1% of isolates. Based on our findings, we proposed various strategies to improve the 4CMenB vaccine and broaden the coverage of N. meningitidis strains.


Assuntos
Infecções Meningocócicas , Vacinas Meningocócicas , Neisseria meningitidis Sorogrupo B , Neisseria meningitidis , Humanos , Antígenos de Bactérias/genética , Infecções Meningocócicas/prevenção & controle , Vacinas Meningocócicas/genética , Eficácia de Vacinas , Neisseria meningitidis Sorogrupo B/genética , Adesinas Bacterianas/genética , Neisseria meningitidis/genética , Neisseria , Biologia Computacional , Prognóstico
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...