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1.
Sci Total Environ ; 942: 173757, 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-38851329

RESUMO

This study identified the occurrence of Holocene chronology hiatuses in the sedimentary record of the Patos-Mirim system caused by river avulsion processes, as well as evidence of sharp anthropogenic changes in the surrounding region of the lagoon water bodies. The presence of chronology hiatuses demonstrates the importance of considering the disturbance effect of paleo-drainage processes on the paleoenvironmental resolution and expression of the sedimentary record of such coastal plains. Anthropogenic activities especially those related to agriculture and forestry have increased significantly during the great acceleration, resulting in modifications of both the landscape and the environmental conditions of the lagoon bodies. Such impacts were clearly reflected in the sedimentary record where abrupt changes in palynological trends, sedimentary DNA, isotopic and granulometric analyses were inferred. The climatic conditions combined with regressive sea level can explain the chronology hiatuses. Pollen analyses demonstrated changes in the landscape, particularly indicated by the shift from Cyperaceae to Poaceae dominance after the 1960 CE. Therefore, all proxies together demonstrate the modification in the landscape and changes in the environment, clearly influenced by anthropogenic action from unsustainable agricultural practices.


Assuntos
Agricultura , Monitoramento Ambiental , Sedimentos Geológicos , Rios , Movimentos da Água
2.
Appl Opt ; 63(13): 3641-3647, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38856550

RESUMO

This paper presents a nondestructive method for accurately identifying internal flaws in metal plates, which is crucial for ensuring structural integrity in safety-critical applications. The technique relies on analyzing laser-induced ultrasound (LIU) longitudinal wave time-of-flight, as demonstrated through a theoretical five-layer model. Experimental validation was conducted using a piezo-sensor in contact with a slab containing millimetric artificial cavities immersed in air, resulting in a discrepancy of 5.05%. In contrast, experiments performed in a water medium exhibited a lower discrepancy of 2.5%. (Discrepancy refers to differences between measurements obtained through an experimental time-of-flight analysis and caliper measurements.) The results obtained in water-based experiments affirm the accuracy of the proposed model. B-scan measurements and the five-layer model were utilized to generate 2D reconstructed images, enabling precise localization and sizing of cavities and kissing bonds between plates, finding an average size of kissing bond of 30 µm. In conclusion, the proposed five-layer model, based on a longitudinal wave time-of-flight analysis, provides a straightforward framework for an easy cavity and kissing bond measurements in metal plates.

3.
FEMS Microbiol Rev ; 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38760882

RESUMO

The study of how micro-organisms detect and respond to different stresses has a long history of producing fundamental biological insights while being simultaneously of significance in many applied microbiological fields including infection, food and drink manufacture, and industrial and environmental biotechnology. This is well illustrated by the large body of work on acid stress. Numerous different methods have been used to understand the impacts of low pH on growth and survival of micro-organisms, ranging from studies of single cells to large and heterogeneous populations, from the molecular or biophysical to the computational, and from well-understood model organisms to poorly defined and complex microbial consortia. Much is to be gained from an increased general awareness of these methods, and so the present review looks at examples of the different methods that have been used to study acid resistance, acid tolerance, and acid stress responses, and the insights they can lead to, as well as some of the problems involved in using them. We hope this will be of interest both within and well beyond the acid stress research community.

4.
J Phys Condens Matter ; 36(35)2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38776954

RESUMO

Ordered and disordered semiconductor superlattices represent structures with completely opposed properties. For instance, ordered superlattices exhibit extended Bloch-like states, while disordered superlattices present localized states. These characteristics lead to higher conductance in ordered superlattices compared to disordered ones. Surprisingly, disordered dimer superlattices, which consist of two types of quantum wells with one type always appearing in pairs, exhibit extended states. The percentage of dissimilar wells does not need to be large to have extended states. Furthermore, the conductance is intermediate between ordered and disordered superlattices. In this work, we explore disordered dimer superlattices in graphene. We calculate the transmission and transport properties using the transfer matrix method and the Landauer-Büttiker formalism, respectively. We identify and discuss the main energy regions where the conductance of random dimer superlattices in graphene is intermediate to that of ordered and disordered superlattices. We also analyze the resonant energies of the double quantum well cavity and the electronic structure of the host gated graphene superlattice (GGSL), finding that the coupling between the resonant energies and the superlattice energy minibands gives rise to the extended states in random dimer GGSLs.

5.
Radiologia (Engl Ed) ; 66(2): 114-120, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38614528

RESUMO

OBJECTIVES: To evaluate if the tumour perfusion at the initial MRI scan is a marker of prognosis for survival in patients diagnosed with High Grade Gliomas (HGG). To analyse the risk factors which influence on the mortality from HGG to quantify the overall survival to be expected in patients. PATIENTS AND METHODS: The patients diagnosed with HGG through a MRI scan in a third-level hospital between 2017 and 2019 were selected. Clinical and tumour variables were collected. The survival analysis was used to determine the association between the tumour perfusion and the survival time. The relation between the collected variables and the survival period was assessed through Wald's statistical method, measuring the relationship via Cox's regression model. Finally, the type of relationship that exists between the tumour perfusion and the survival was analysed through the Lineal Regression method.Those statistical analysis were carried out using the software SPSS v.17. RESULTS: 38 patients were included (average age: 61.1 years old). The general average survival period was 20.6 months. A relationship between the tumour perfusion at the MRI scan and the overall survival has been identified, in detail, a group with intratumor values of relative cerebral blood volume (rCBV)>3.0 has shown a significant decline in the average survival period with regard to the average survival period of the group with values <3.0 (14.6 months vs. 22.8 months, p = 0.046). It has also been proved that variables like Karnofsky's scale and the response time since the intervention significantly influence on the survival period. CONCLUSIONS: It has become evident that the tumour perfusion via MRI scan has a prognostic value in the initial analysis of HGG. The average survival period of patients with rCBV less than or equal to 3.0 is significantly higher than those patients whose values are higher, which allows to be more precise with the prognosis of each patient.


Assuntos
Encéfalo , Glioma , Humanos , Pessoa de Meia-Idade , Prognóstico , Perfusão , Glioma/diagnóstico por imagem , Imageamento por Ressonância Magnética
6.
Heliyon ; 10(6): e27359, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38501005

RESUMO

TiO2 thin films with mixtures of the anatase, rutile, and brookite phases were deposited on glass substrates via magnetron sputtering. Based on XRD and Raman results, the TiO2-0.47 and TiO2-3.47 films principally contained the brookite phase, while the TiO2-1.27 and TiO2-2.13 films were primarily anatase. The capacities of the TiO2 films to adsorb heavy metals were tested with Cr(VI) and Fe(III) solutions, and the maximum Cr(VI) and Fe(III) adsorption capacities were realized with the TiO2-0.47 film (334.5 mg/g) and TiO2-3.47 film (271.3 mg/g), respectively. SEM‒EDS results revealed the presence of Cr and Fe on the surfaces of the films, thus corroborating the ability of the TiO2 films to adsorb and remove heavy metals. They are strong candidates for use in wastewater treatment plants.

7.
Neurologia (Engl Ed) ; 39(2): 127-134, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38272259

RESUMO

INTRODUCTION: Huntington disease (HD) is a hereditary neurodegenerative disorder. Thanks to predictive diagnosis, incipient clinical characteristics have been described in the prodromal phase. OBJECTIVE: To compare performance in cognitive tasks of carriers (HDC) and non-carriers (non-HDC) of the huntingtin gene and to analyse the variability in performance as a function of disease burden and proximity to the manifest stage (age of symptom onset). METHOD: A sample of 146 participants in a predictive diagnosis of HD programme were divided into the HDC (41.1%) and non-HDC groups (58.9%). Mathematical formulae were used to calculate disease burden and proximity to the manifest stage in the HDC group; these parameters were correlated with neuropsychological performance. RESULTS: Significant differences were observed between groups in performance on the Mini-Mental State Examination (MMSE), Stroop-B, Symbol-Digit Modalities Test (SDMT), and phonological fluency. In the HDC group, correlations were observed between disease burden and performance on the MMSE, Stroop-B, and SDMT. The group of patients close to the manifest stage scored lowest on the MMSE, Stroop-B, Stroop-C, SDMT, and semantic verbal fluency. According to the multivariate analysis of covariance, the MMSE effect shows statistically significant differences in disease burden and proximity to onset of symptoms. CONCLUSIONS: Members of the HDC group close to the manifest phase performed more poorly on tests assessing information processing speed and attention. Prefrontal cognitive dysfunction appears early, several years before the motor diagnosis of HD.


Assuntos
Transtornos Cognitivos , Disfunção Cognitiva , Doença de Huntington , Humanos , Doença de Huntington/genética , Cognição , Efeitos Psicossociais da Doença
8.
Reprod Biol ; 24(1): 100848, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38199161

RESUMO

Growth hormone is a key endocrine factor for metabolic adaptations to lactation and optimal reproductive function of the dairy cow. This study aimed to analyze the expression of GH and its receptor (GHR) in ovarian follicles, along with metabolic biomarkers, during the resumption of the postpartum follicular development, and to analyze the immunolocalization and protein expression of GH and GHR in preovulatory follicles. Thirty-six dairy cows were grouped according to the postpartum days (PPD) until the establishment of the first dominant follicle in: cows that established their first dominant follicle at fewer postpartum days (FPPD group; n = 15) and cows that established their first dominant follicle at more postpartum days (MPPD group; n = 22). For a second analysis, the same cows were regrouped according to the calving season (S), into cows calving in autumn (n = 20) and cows calving in winter (n = 17). During the PP, blood and follicular aspirates were obtained at two timepoints (T): when the first dominant follicle was established (T1, day 9 ± 2), and when the preovulatory follicle was established (T2, day 45 ± 2). Also, six dairy cows were ovariectomized in proestrus and ovarian histological sections were obtained. Growth hormone mRNA was detected in granulose cells from ovarian follicle sampled during PP. A PPD × T interaction was observed for GHR mRNA, where it was greater in the FPPD cows than in the MPPD cows at T1. Metabolic biomarkers and reproductive hormones showed differences or interaction between PPD, T, S, depending on the case. Also, GH and GHR were immunolocalized in granulosa and theca interna cells of preovulatory follicles. These results confirm the expression of GH and GHR in the mature ovarian follicles of dairy cows and show a possible association between greater GHR expression and an earlier resumption of postpartum follicular development.


Assuntos
Hormônio do Crescimento , Período Pós-Parto , Feminino , Humanos , Bovinos , Animais , Período Pós-Parto/fisiologia , Folículo Ovariano/fisiologia , Lactação/fisiologia , RNA Mensageiro , Biomarcadores , Ovulação/fisiologia
9.
Rev Esp Anestesiol Reanim (Engl Ed) ; 71(1): 54-57, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37678455

RESUMO

Jarcho-Levin syndrome is an eponym used to describe a spectrum of small thoracic skeletal dysplasias with variable involvement of vertebrae and ribs. Initially considered lethal, it is currently compatible with life in its mildest forms. Bone alterations that lead to a restrictive respiratory pattern, recurrent respiratory infections and particular phenotype, can make perioperative anesthetic management difficult. The proper assessment of the airway is of special interest because it presents predictors of a difficult airway, as well as the prevention, early diagnosis and adequate treatment of respiratory failure. We present the case of a patient with Jarcho-Levin Syndrome who underwent vertebral distraction surgery, with its most notable implications in anesthetic management.


Assuntos
Anormalidades Múltiplas , Anestésicos , Hérnia Diafragmática , Humanos , Hérnia Diafragmática/cirurgia , Anormalidades Múltiplas/diagnóstico , Anormalidades Múltiplas/cirurgia , Coluna Vertebral
10.
J Phys Condens Matter ; 36(6)2023 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-37903438

RESUMO

Gaussian and Gaussian-related structures are quite attractive due to its versatility to modulate the electronic transport, including its possibility as electron filters. Here, we show that these non-conventional profiles are not the exception when dealing with Fermi velocity barriers in monolayer graphene. In particular, we show that Gaussian Fermi velocity graphene barriers (G-FVGBs) and Gaussian-pulsed-like Fermi velocity graphene superlattices (GPL-FVGSLs) can serve as electron band-pass filters and oscillating conductance structures. We reach this conclusion by theoretically studying the transmission and transport properties of the mentioned structures. The study is based on the continuum model, the transfer matrix method and the Landauer-Büttiker formalism. We find nearly flat transmission bands or pass bands for G-FVGBs modulable through the system parameters. The pass bands improve as the maximum ratio of Fermi velocities (ξmax) increases, however its omnidirectional range is reduced. These characteristics result in a decaying conductance (integrated transmission) withξmax. The integrated transmission remains practically unaltered with the size of the system due to the saturation of the electron pass band filtering. In the case of GPL-FVGSLs the GPL profile results in regions of high transmission probability that can merge as flat transmission minibands if the pulse fraction and the superlattice parameters are appropriately tuned. The GPL profile also results in conductance (integrated transmission) oscillations that can be multiplied or reduced in number by adjusting the pulse fraction as well as the superlattice parameters.

12.
Sci Total Environ ; 905: 167873, 2023 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-37852497

RESUMO

The objective of this investigation is to evaluate the recent changes in the accumulation of organic matter and carbon on the Yahuarcaca lake system, by means of a multiproxy paleolimnological study. The methodology based on lithological descriptions of 210Pb/137Cs-dated cores allowed us to infer the centennial sedimentation processes and carbon accumulation rates. Sedimentary facies, grain size, magnetic susceptibility, loss on ignition, carbonate, chlorophyll derivatives, stable isotopes of δ13C/δ15N, and carbon accumulation rate were analyzed. LANDSAT and photographic record of satellite images were used to reconstruct the historical geomorphological evolution of the Lake. Sediment cores yielded basal ages of 1827 and 1828 Common Era, representing the formation of lakes as a consequence of the Amazon meandering process. Two main paleolimnological stages were identified, with a boundary transition set at 1980-1984 Common Era, attributed to the geomorphological closure and complete lake separation from the Amazon and the onset of full lentic conditions. This inference was mainly based on both sharp increases in the sedimentation rate from 0.2 to >1 cm yr-1 and carbon accumulation that increased seven-fold (from 2 to 14 g m-2 yr-1) from 1980 to 1984 Common Era. The flood-pulse and connection to the Amazon defined the magnitude of organic inputs, where areas more distant/isolated from the river showed higher accumulation of carbon from autochthonous production, with an average of 8.9 % and 1.10 g m-2 yr-1 (carbon accumulation rate). Those areas closer and connected to the river were strongly related to the interannual hydrological variability, with a lower mean carbon content (5.9 %) and 0.73 g m-2 yr-1 (carbon accumulation rate). We concluded that carbon burial was highest within the most distant spot from the Amazon River because of the weaker connection to the river itself and the more stable lentic conditions for net sedimentation.

13.
Theriogenology ; 211: 241-247, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37677868

RESUMO

Glucocorticoids (GCs) act through their receptor (GR) as regulators in different biological processes such as reproduction. In the absence of GCs, the GR remains inactive in the cytoplasm by associating with heat shock proteins (HSPs), which act as molecular chaperones, among which the most relevant are HSP90 and HSP70. Cytoplasmic GC-activated GR mediates non-genomic effects, interacting with members of signaling pathways such as PI3K/Akt, which participates in several metabolic processes, including the insulin signaling pathway. The aim of the present study was to evaluate possible associations between the cytoplasmic GR and the main intermediates of the insulin signaling pathway and HSP90 and HSP70 in ovaries of dairy cows. To this end, the protein expression of cytoplasmic GR, key members of the insulin signaling pathway, and HSPs was evaluated in ovarian preovulatory follicles of non-lactating Holstein cows in proestrus. Positive associations were observed between protein expression of GR and HSP90, IRS1, pIRS1, PI3K and pAkt (p < 0.05; ß > 0) in granulosa cells of dominant follicles of dairy cows. Instead, in theca cells, no associations were observed between protein expression of GR and members of the insulin signaling pathway or HSPs. These data provide evidence of the possible association between the non-genomic mechanisms of action of the GR and the insulin signaling pathway in the bovine ovary.


Assuntos
Glucocorticoides , Receptores de Glucocorticoides , Feminino , Animais , Bovinos , Receptores de Glucocorticoides/genética , Proteínas de Choque Térmico/genética , Insulina , Ovário , Fosfatidilinositol 3-Quinases , Proteínas de Choque Térmico HSP70 , Transdução de Sinais
15.
Surg Endosc ; 37(10): 7774-7783, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37580582

RESUMO

BACKGROUND: The length of conventional single-use cholangioscopes poses a challenge for percutaneous or laparoscopic approaches for direct visualization of the biliary tract. The aim of this retrospective observational clinical study was to assess the use of a dedicated percutaneous short single-operator cholangioscope (PSSOC) for diagnosis and treatment of benign or malignant biliary diseases. METHODS: Retrospective analysis of a prospectively maintained database including all consecutive patients undergoing percutaneous transhepatic cholangioscopy with the PSSOC between 06/2021 and 01/2023. RESULTS: Forty patients were included (22F/18 M, age 58.7 ± 16.7 years). The diagnostic and therapeutic management plan was based on procedural findings. Indications were bile duct obstruction associated with complex anatomy (n = 13), choledocholithiasis (n = 11), suspected malignant stenosis of the biliary tract (n = 11), biliary stent placement (n = 2) and removal (n = 1), and failed endoscopic retrograde cholangiopancreatography (n = 2). The cholangioscopies were diagnostic (n = 5), therapeutic (n = 20) or both simultaneously (n = 15). The most frequent procedures were electrohydraulic lithotripsy (n = 25) and biopsy sampling (n = 12). Complications occurred in 7 cases (17.5%), including cholangitis (n = 4, B2), pleural perforation (n = 1, B2), portal bleeding (n = 1, B3), and Tako-Tsubo syndrome (n = 1, B3), classified according to the Society of Interventional Radiology classification. Intraprocedural visual diagnosis was confirmed by the histopathologic result in 11/12 patients in which biopsies were performed (91.7%). PSSOC was relevant to avoid surgery in 2 patients (5%) with indeterminate strictures, allowing to rule out malignancy and treat the lithiasis. CONCLUSIONS: Direct visualization of the biliary tract enabled targeted biopsies for histopathological diagnosis. The visual and histopathological diagnoses were concordant in all but one case. Percutaneous cholangioscopy with a dedicated PSSOC allows to optimize identification and treatment of complex biliary disease including biliary lithiasis while assessing bile duct patency. The clinical use of the novel PSSOC system was safe and effective and could prevent surgical exploration in select patients.


Assuntos
Neoplasias dos Ductos Biliares , Doenças da Vesícula Biliar , Laparoscopia , Litíase , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Litíase/patologia , Estudos Retrospectivos , Endoscopia do Sistema Digestório/métodos , Colangiopancreatografia Retrógrada Endoscópica/métodos , Ductos Biliares/patologia , Doenças da Vesícula Biliar/patologia , Neoplasias dos Ductos Biliares/patologia
16.
Public Health ; 222: 85-91, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37531714

RESUMO

OBJECTIVES: The aims of this study were (1) to examine the differences in the mode of commuting and barriers to active commuting to university between the sexes (men and women) and in different countries (Chile and Spain); and (2) to analyse the association between the mode of commuting and the perceived barriers for male and female university students in Chile and Spain. STUDY DESIGN: This cross-sectional study took place between April 2017 and May 2018 in Chile and Spain. METHODS: The study population included 2269 university students (53.0% women). The mode of commuting and barriers to active commuting to university were assessed by a self-reported questionnaire. Multinomial logistic regression analysis was used to examine the associations. RESULTS: In both sexes, public and private transport were the main modes of commuting used in Chile and Spain, respectively, followed by active commuting in all participants, except for female students in Spain. Women perceived more environmental and psychosocial barriers compared to men (Chile: P < 0.001; Spain: P = 0.006). Perceived environmental barriers showed higher significant differences between students in Chile and Spain (P < 0.05). Private commuters reported a larger proportion of psychosocial barriers compared to active commuters (Chile: men P = 0.001, women P < 0.001; Spain: men P < 0.001, women P = 0.036). CONCLUSIONS: The study findings suggest that the mode of commuting and the barriers to active commuting to university may be influenced by sex and country.


Assuntos
Meios de Transporte , Caminhada , Humanos , Masculino , Feminino , Universidades , Estudos Transversais , Espanha , Inquéritos e Questionários , Ciclismo
17.
QJM ; 116(10): 835-844, 2023 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-37449904

RESUMO

BACKGROUND: Lactate is an already recognized biomarker for short-term mortality in emergency medical services (EMS). However, how different levels of lactate are associated with short-, mid- and long-term outcomes should be unveiled. AIM: To determine how different categories of hyperlactatemia are associated with mortality. We also aim to clinically characterize hyperlactatemia groups. DESIGN: A multicenter, prospective, observational study performed between January 2019 and February 2022, considering 48 basic life support units and 5 advanced life support units referring to 4 tertiary care hospitals (Spain). Patients were recruited from phone requests for emergency assistance in adults, evacuated to emergency departments. The primary outcome was in-hospital mortality from any cause within the first to the 365-day period following EMS attendance. The main measures were demographical and biochemical variables, prehospital advanced life support techniques used and patient condition categorized in 24 diseases. METHODS: Univariate and Cox regression analysis. RESULTS: A total of 5072 participants fulfilled inclusion criteria. Group #1 (non-hyperlactatemia) was composed of 2389 subjects (47.1%), Group #2 (mild hyperlactatemia) of 1834 (36.1%), Group #3 (hyperlactatemia) of 333 (6.6%) and, finally, Group #4 (severe hyperlactatemia) of 516 (10.2%). The 1-day mortality was 0.2%, 1.1%, 9% and 22.3% in the four lactate groups, respectively. Long-term mortality (365 days) was 10.2%, 22.7%, 38.7% and 46.7% in the four lactate groups, respectively. Differences between patients' conditions of lactatemia groups were also found. CONCLUSIONS: Our results demonstrated that prehospital lactate categories were associated with short- and long-term outcomes in a different manner. These results will allow EMS to establish different risk states according to the prehospital lactate categories.

18.
Braz J Med Biol Res ; 56: e12713, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37493771

RESUMO

Mesenchymal stromal/stem cells stem (MSC) have been widely studied due to their great potential for application in tissue engineering and regenerative and translational medicine. In MSC-based therapy for human diseases, cell proliferation is required to obtain a large and adequate number of cells to ensure therapeutic efficacy. During in vitro culture, cells are under an artificial environment and manipulative stress that can affect genetic stability. Several regulatory agencies have established guidelines to ensure greater safety in cell-based regenerative and translational medicine, but there is no specific definition about the maximum number of passages that ensure the lowest possible risk in MSC-based regenerative medicine. In this context, the aim of this study was to analyze DNA damage and chromosome alterations in adipose-derived mesenchymal stromal cells (ADMSC) until the eleventh passage and to provide additional subsidies to regulatory agencies related to number of passages in these cells. Thus, two methods in genetic toxicology were adopted: comet assay and micronucleus test. The comet assay results showed an increase in DNA damage from the fifth passage onwards. The micronucleus test showed a statistically significant increase of micronucleus from the seventh passage onwards, indicating a possible mutagenic effect associated with the increase in the number of passages. Based on these results, it is important to emphasize the need to assess genetic toxicology and inclusion of new guidelines by regulatory agencies to guarantee the safety of MSC-based therapies for human diseases.


Assuntos
Células-Tronco Mesenquimais , Humanos , Engenharia Tecidual , Instabilidade Genômica , Proliferação de Células , Mutagênese , Diferenciação Celular , Células Estromais
19.
Nat Commun ; 14(1): 4251, 2023 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-37460545

RESUMO

Fibroblasts have a considerable functional and molecular heterogeneity and can play various roles in the tumor microenvironment. Here we identify a pro-tumorigenic IL1R1+, IL-1-high-signaling subtype of fibroblasts, using multiple colorectal cancer (CRC) patient single cell sequencing datasets. This subtype of fibroblasts is linked to T cell and macrophage suppression and leads to increased cancer cell growth in 3D co-culture assays. Furthermore, both a fibroblast-specific IL1R1 knockout and IL-1 receptor antagonist Anakinra administration reduce tumor growth in vivo. This is accompanied by reduced intratumoral Th17 cell infiltration. Accordingly, CRC patients who present with IL1R1-expressing cancer-associated-fibroblasts (CAFs), also display elevated levels of immune exhaustion markers, as well as an increased Th17 score and an overall worse survival. Altogether, this study underlines the therapeutic value of targeting IL1R1-expressing CAFs in the context of CRC.


Assuntos
Fibroblastos Associados a Câncer , Neoplasias Colorretais , Humanos , Fibroblastos Associados a Câncer/patologia , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Fibroblastos/patologia , Tolerância Imunológica , Terapia de Imunossupressão , Microambiente Tumoral , Proliferação de Células , Receptores Tipo I de Interleucina-1/genética
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