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1.
Am J Cancer Res ; 14(7): 3626-3638, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39113863

RESUMO

Anaplastic thyroid cancer (ATC) is a clinically aggressive form of undifferentiated thyroid cancer with limited treatment options. Tumor-associated macrophages (TAMs) constitute over 50% of ATC-infiltrating cells, and their presence is associated with a poor prognosis. We have previously shown that paracrine signals released by ATC cells induced pro-tumor M2-like polarization of human monocytes. However, which soluble factors derived from ATC cells drive monocyte activation, are largely unknown. In this study we investigated the participation of transforming growth factor ß1 (TGFß1) on the phenotype of macrophage activation induced by ATC cell-derived conditioned media (CM). THP-1 cells exposed to CM derived from ATC cells and recombinant human TGFß1 induced M2-like macrophage polarization, showing high CD163 and Dectin1 expression. Moreover, we showed that TGFß1 induced the messenger RNA (mRNA) and protein expression of the transcription factors SNAIL and SLUG. Accordingly, increased TGFß1 secretion from ATC cells was confirmed by enzyme-linked immunosorbent assay (ELISA). Addition of SB431542, a TGFß receptor inhibitor, significantly decreased the Dectin1, CD163, SNAIL and SLUG expression stimulated by ATC cell-derived CM. We validated the clinical significance of the expression of TGFß ligands, their receptors, as well as SNAIL and SLUG in human ATC by analyzing public microarray datasets. We found that the expression of the main TGFß ligands, TGFß1 and TGFß3, along with their receptors, TGFR1 and TGFR2, as well as SLUG, was significantly higher in human ATC tissue samples than in normal thyroid tissues. Our findings indicate that ATC cell-secreted TGFß1 may play a key role in M2-like macrophage polarization of human monocytes and in the up-regulation of SNAIL and SLUG transcription factors. Thus, ours results uncovered a novel mechanism involved in the activation of TAMs by soluble factors released by ATC cells, which suggest potential therapeutic targets for ATC.

2.
PNAS Nexus ; 3(7): pgae263, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39081784

RESUMO

Political polarization has become a growing concern in democratic societies, as it drives tribal alignments and erodes civic deliberation among citizens. Given its prevalence across different countries, previous research has sought to understand under which conditions people tend to endorse extreme opinions. However, in polarized contexts, citizens not only adopt more extreme views but also become correlated across issues that are, a priori, seemingly unrelated. This phenomenon, known as "ideological sorting", has been receiving greater attention in recent years but the micro-level mechanisms underlying its emergence remain poorly understood. Here, we study the conditions under which a social dynamic system is expected to become ideologically sorted as a function of the mechanisms of interaction between its individuals. To this end, we developed and analyzed a multidimensional agent-based model that incorporates two mechanisms: homophily (where people tend to interact with those holding similar opinions) and pairwise-coherence favoritism (where people tend to interact with ingroups holding politically coherent opinions). We numerically integrated the model's master equations that perfectly describe the system's dynamics and found that ideological sorting only emerges in models that include pairwise-coherence favoritism. We then compared the model's outcomes with empirical data from 24,035 opinions across 67 topics and found that pairwise-coherence favoritism is significantly present in datasets that measure political attitudes but absent across topics not considered related to politics. Overall, this work combines theoretical approaches from system dynamics with model-based analyses of empirical data to uncover a potential mechanism underlying the pervasiveness of ideological sorting.

3.
Int J Mol Sci ; 25(14)2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-39062847

RESUMO

Mesenchymal stem/stromal cells (MSCs) and their extracellular vesicles (MSC-EVs) have been described to have important roles in tissue regeneration, including tissue repair, control of inflammation, enhancing angiogenesis, and regulating extracellular matrix remodeling. MSC-EVs have many advantages for use in regeneration therapies such as facility for dosage, histocompatibility, and low immunogenicity, thus possessing a lower possibility of rejection. In this work, we address the potential activity of MSC-EVs isolated from adipose-derived MSCs (ADMSC-EVs) cultured on cross-linked dextran microcarriers, applied to test the scalability and reproducibility of EV production. Isolated ADMSC-EVs were added into cultured human dermal fibroblasts (NHDF-1), keratinocytes (HaCat), endothelial cells (HUVEC), and THP-1 cell-derived macrophages to evaluate cellular responses (i.e., cell proliferation, cell migration, angiogenesis induction, and macrophage phenotype-switching). ADMSC viability and phenotype were assessed during cell culture and isolated ADMSC-EVs were monitored by nanotracking particle analysis, electron microscopy, and immunophenotyping. We observed an enhancement of HaCat proliferation; NHDF-1 and HaCat migration; endothelial tube formation on HUVEC; and the expression of inflammatory cytokines in THP-1-derived macrophages. The increased expression of TGF-ß and IL-1ß was observed in M1 macrophages treated with higher doses of ADMSC-EVs. Hence, EVs from microcarrier-cultivated ADMSCs are shown to modulate cell behavior, being able to induce skin tissue related cells to migrate and proliferate as well as stimulate angiogenesis and cause balance between pro- and anti-inflammatory responses in macrophages. Based on these findings, we suggest that the isolation of EVs from ADMSC suspension cultures makes it possible to induce in vitro cellular responses of interest and obtain sufficient particle numbers for the development of in vivo concept tests for tissue regeneration studies.


Assuntos
Proliferação de Células , Vesículas Extracelulares , Macrófagos , Células-Tronco Mesenquimais , Humanos , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/citologia , Vesículas Extracelulares/metabolismo , Macrófagos/metabolismo , Macrófagos/citologia , Movimento Celular , Células THP-1 , Fibroblastos/metabolismo , Fibroblastos/citologia , Células Endoteliais da Veia Umbilical Humana/metabolismo , Técnicas de Cultura de Células/métodos , Células Cultivadas , Queratinócitos/metabolismo , Queratinócitos/citologia , Citocinas/metabolismo
4.
Immunol Invest ; 53(7): 1030-1091, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38913937

RESUMO

INTRODUCTION: An event of increasing interest during host-pathogen interactions is the polarization of patrolling/naive monocytes (MOs) into macrophage subsets (MФs). Therapeutic strategies aimed at modulating this event are under investigation. METHODS: This review focuses on the mechanisms of induction/development and profile of MФs polarized toward classically proinflammatory (M1) or alternatively anti-inflammatory (M2) phenotypes in response to bacteria, fungi, parasites, and viruses. RESULTS AND DISCUSSION: It highlights nuclear, cytoplasmic, and cell surface receptors (pattern recognition receptors/PPRs), microenvironmental mediators, and immune signaling. MФs polarize into phenotypes: M1 MФs, activated by IFN-γ, pathogen-associated molecular patterns (PAMPs, e.g. lipopolysaccharide) and membrane-bound PPRs ligands (TLRs/CLRs ligands); or M2 MФs, induced by interleukins (ILs-4, -10 and -13), antigen-antibody complexes, and helminth PAMPs. Polarization toward M1 and M2 profiles evolve in a pathogen-specific manner, with or without canonicity, and can vary widely. Ultimately, this can result in varying degrees of host protection or more severe disease outcome. On the one hand, the host is driving effective MФs polarization (M1 or M2); but on the other hand, microorganisms may skew the polarization through virulence factors to increase pathogenicity. Cellular/genomic reprogramming also ensures plasticity of M1/M2 phenotypes. Because modulation of polarization can occur at multiple points, new insights and emerging perspectives may have clinical implications during the inflammation-to-resolution transition; translated into practical applications as for therapeutic/vaccine design target to boost microbicidal response (M1, e.g. triggering oxidative burst) with specifics PAMPs/IFN-γ or promote tissue repair (M2, increasing arginase activity) via immunotherapy.


Monocytes are white blood cells (leukocytes) that help fight off various types of aggressive agents, including microorganisms (bacteria, fungi, viruses, and parasites), and help maintain the healthy balance of the human body. These cells differentiate into specific macrophages in tissues such as the lungs, heart, liver, skin, and brain. The present review focuses on the peculiar cellular properties that macrophages can acquire during the human immune response to infectious diseases. In this regard, it is discussed that macrophages are didactically divided into M1 and M2 subtypes. The first subtype (M1) is responsible for fighting pathogens and causing inflammation. The second subtype (M2) is mainly responsible for healing and repairing damaged tissue. Current knowledge shows that although both subtypes are involved in the same immune response aimed at protecting the human body, these M1 and M2 profiles have different characteristics that have implications for therapeutic measures such as developing specific drugs or vaccines to balance the immune response against a given pathogen and promote a complete cure of the disease. Alongside the therapeutic impacts, this review also looks at the characteristics that allow aggressive microorganisms to counteract the immune response developed by these M1 and M2 cell profiles. It highlights how exactly there can be greater protection or detriment to the human host against a given microorganism when there is a predilection to develop a more abundant immune response from one of the two profiles (M1 or M2).


Assuntos
Interações Hospedeiro-Patógeno , Ativação de Macrófagos , Macrófagos , Transdução de Sinais , Fatores de Virulência , Humanos , Transdução de Sinais/imunologia , Animais , Macrófagos/imunologia , Fatores de Virulência/imunologia , Interações Hospedeiro-Patógeno/imunologia , Ativação de Macrófagos/imunologia , Doenças Transmissíveis/imunologia , Receptores de Reconhecimento de Padrão/metabolismo , Receptores de Reconhecimento de Padrão/imunologia
5.
Proc Natl Acad Sci U S A ; 121(26): e2401257121, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38889155

RESUMO

Negative or antagonistic relationships are common in human social networks, but they are less often studied than positive or friendly relationships. The existence of a capacity to have and to track antagonistic ties raises the possibility that they may serve a useful function in human groups. Here, we analyze empirical data gathered from 24,770 and 22,513 individuals in 176 rural villages in Honduras in two survey waves 2.5 y apart in order to evaluate the possible relevance of antagonistic relationships for broader network phenomena. We find that the small-world effect is more significant in a positive world with negative ties compared to an otherwise similar hypothetical positive world without them. Additionally, we observe that nodes with more negative ties tend to be located near network bridges, with lower clustering coefficients, higher betweenness centralities, and shorter average distances to other nodes in the network. Positive connections tend to have a more localized distribution, while negative connections are more globally dispersed within the networks. Analysis of the possible impact of such negative ties on dynamic processes reveals that, remarkably, negative connections can facilitate the dissemination of information (including novel information experimentally introduced into these villages) to the same degree as positive connections, and that they can also play a role in mitigating idea polarization within village networks. Antagonistic ties hold considerable importance in shaping the structure and function of social networks.


Assuntos
População Rural , Apoio Social , Humanos , Honduras , Rede Social , Masculino , Feminino , Relações Interpessoais , Análise de Rede Social
6.
Front Bioeng Biotechnol ; 12: 1410863, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38903186

RESUMO

Tissue-engineered vascular grafts (TEVGs) poised for regenerative applications are central to effective vascular repair, with their efficacy being significantly influenced by scaffold architecture and the strategic distribution of bioactive molecules either embedded within the scaffold or elicited from responsive tissues. Despite substantial advancements over recent decades, a thorough understanding of the critical cellular dynamics for clinical success remains to be fully elucidated. Graft failure, often ascribed to thrombogenesis, intimal hyperplasia, or calcification, is predominantly linked to improperly modulated inflammatory reactions. The orchestrated behavior of repopulating cells is crucial for both initial endothelialization and the subsequent differentiation of vascular wall stem cells into functional phenotypes. This necessitates the TEVG to provide an optimal milieu wherein immune cells can promote early angiogenesis and cell recruitment, all while averting persistent inflammation. In this study, we present an innovative TEVG designed to enhance cellular responses by integrating a physicochemical gradient through a multilayered structure utilizing synthetic (poly (ester urethane urea), PEUU) and natural polymers (Gelatin B), thereby modulating inflammatory reactions. The luminal surface is functionalized with a four-arm polyethylene glycol (P4A) to mitigate thrombogenesis, while the incorporation of adhesive peptides (RGD/SV) fosters the adhesion and maturation of functional endothelial cells. The resultant multilayered TEVG, with a diameter of 3.0 cm and a length of 11 cm, exhibits differential porosity along its layers and mechanical properties commensurate with those of native porcine carotid arteries. Analyses indicate high biocompatibility and low thrombogenicity while enabling luminal endothelialization and functional phenotypic behavior, thus limiting inflammation in in-vitro models. The vascular wall demonstrated low immunogenicity with an initial acute inflammatory phase, transitioning towards a pro-regenerative M2 macrophage-predominant phase. These findings underscore the potential of the designed TEVG in inducing favorable immunomodulatory and pro-regenerative environments, thus holding promise for future clinical applications in vascular tissue engineering.

7.
Front Chem ; 12: 1372292, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38606079

RESUMO

The concentration effect of Tradescantia spathacea (T. spathacea) as corrosion inhibitor of API 5L X52 steel in 0.5 M of H2SO4 was studied here through electrochemical and gravimetric techniques. To achieve it, samples of the material were prepared to be submitted to each of the tests. Results from electrochemical impedance spectroscopy (EIS) showed that there was an optimum concentration of the inhibitor in which is reached the maximum inhibition efficiency, displaying the best inhibition characteristics for this system with a maximum inhibition of 89% by using 400 ppm. However, the efficiency decreased until 40% when the temperature was increased to 60°C. Potentiodynamic polarization curves (PDP) revealed that some of the present compounds of T. spathacea may affect anodic and cathodic process, so it can be classified as a mix-type corrosion inhibitor for API 5L X52 in sulfuric acid. Also, this compound followed an adsorption mechanism; this can be described through a Frumkin isotherm with an adsorption standard free energy difference (ΔG°) of -56.59 kJmol-1. Metal surface was studied through scanning electron microscope, results revealed that by adding inhibitor, the metal surface is protected; also, they evidenced low damages compared with the surface with no inhibitor. Finally, Tradescantia spathacea inhibited the corrosion process with 82% efficiency.

8.
Front Vet Sci ; 11: 1381162, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38659456

RESUMO

Tamoxifen (TAM) is widely utilized in the prevention and treatment of human breast cancer and has demonstrated the potential to modulate the immune response. It has been proposed as a therapeutic tool for immune-mediated diseases. TAM has been investigated as a possible treatment for asthma-like conditions in horses, revealing specific impacts on the innate immune system. While the effects of TAM on equine neutrophils are well-documented, its influence on lymphocytes and the modulation of the immune response polarization remains unclear. This in vitro study employed peripheral blood mononuclear cells (PBMC) from healthy horses, exposing them to varying concentrations of the TAM and assessing the expression of genes involved in the polarization of the immune response (TBX21, IFNG, GATA3, IL4, IL10, FOXP3, and CTLA4) in PBMC stimulated or not with PMA/ionomycin. Additionally, the effect of TAM over the proportion of regulatory T cells (Treg) was also assessed. TAM did not significantly affect the expression of these genes and Treg at low concentrations. However, at the highest concentration, there was an impact on the expression of GATA3, IL4, IL10, and CTLA4 genes. These alterations in genes associated with a Th2 and regulatory response coincided with a noteworthy increase in drug-associated cytotoxicity but only at concentrations far beyond those achieved in pharmacological therapy. These findings suggest that the effects of TAM, as described in preclinical studies on asthmatic horses, may not be attributed to the modification of the adaptive response.

9.
Materials (Basel) ; 17(8)2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38673181

RESUMO

Biodiesel is a mixture of saturated and unsaturated Fatty Acid Methyl Esters (FAMEs) whose composition affects the corrosion behavior of metal containers during storage. This study examines the effect of the C=C bond present in selected FAMEs (Methyl Stearate, Methyl Oleate, and Methyl Linoleate) in aluminum corrosion in the absence of oxygen. First, mass loss assays were carried out at 100, 200, and 280 °C for 1000 h using pure Methyl Stearate (MS), 5% Methyl Oleate in Methyl Stearate (MS-5% MO), and 5% Methyl Linoleate in Methyl Stearate (MS-5% ML). Next, chemical changes in FAMEs were studied using FTIR, TGA, and GC/MS. SEM/EDS analysis allowed us to inspect the aluminum surfaces and their chemical characterization. We estimated higher corrosion rates for MS assays than those of unsaturated methyl ester mixtures. In a separate set of experiments, we used electrochemical techniques (potentiodynamic polarization, linear polarization resistance, and electrochemical impedance spectroscopy) to investigate aluminum corrosion induced by thermal-degraded products from FAMEs at 100, 200, and 280 °C for 300 h able to dissolve in aqueous extracts. These electrochemical experiments revealed that the products in the aqueous extracts from the unsaturated methyl ester mixture form a passive layer on the Al surface thicker than pure MS at the corresponding degradation temperatures.

10.
Soc Sci Med ; 348: 116783, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38574589

RESUMO

BACKGROUND: While political polarization in policy opinions, preferences, and observance is well established, little is known about whether and how such divisions evolve, and possibly attenuate, over time. Using the COVID-19 pandemic in Brazil as the backdrop, we examine the longitudinal evolution of a highly relevant and polarizing policy: adherence to the COVID-19 vaccination. METHODS: Studies 1 (N = 3346) and 2 (N = 10,214) use nationwide surveys to document initial differences and subsequent changes in vaccination adherence between conservatives ("Bolsonaristas") and non-conservatives ("non-Bolsonaristas"). Study 3 (N = 742) uses an original dataset to investigate belief changes among conservatives and their association with asymmetric changes in vaccination adherence. RESULTS: Despite substantial differences at the early stages of rollout, the gap in vaccination adherence between conservatives and non-conservatives significantly decreased with the passage of time, driven essentially by a much faster uptake among the initially most skeptic-the conservatives. Study 3 demonstrates that the asymmetric changes in vaccination adherence were associated with meaningful belief changes among the conservatives, especially about the perceived effectiveness of the COVID-19 vaccines and the expected adherence of peers to the vaccination campaign. CONCLUSIONS: Together, these studies show that, in a context where the superiority of the promoted policy becomes clear over time and individuals have the opportunity to revisit prior beliefs, even intense political polarization can be attenuated.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Política , Humanos , Brasil , COVID-19/prevenção & controle , COVID-19/epidemiologia , Vacinas contra COVID-19/administração & dosagem , Estudos Longitudinais , Vacinação/estatística & dados numéricos , Vacinação/psicologia , Política de Saúde , SARS-CoV-2
11.
J Phys Condens Matter ; 36(31)2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38670122

RESUMO

Monomer, dimer and trimer semiconductor superlattices are an alternative for bandgap engineering due to the possibility of duplicate, triplicate, and in general multiply the number of minibands and minigaps in a specific energy region. Here, we show that monomer, dimer, and trimer magnetic silicene superlattices (MSSLs) can be the basis for tunable magnetoresistive devices due to the multiplication of the peaks of the tunneling magnetoresistance (TMR). In addition, these structures can serve as spin-valleytronic devices due to the formation of two well-defined spin-valley polarization states by appropriately adjusting the superlattice structural parameters. We obtain these conclusions by studying the spin-valley polarization and TMR of monomer, dimer, and trimer MSSLs. The magnetic unit cell is structured with one seed A with positive magnetization, and one, two, or three seeds B with variable magnetization. The number of B seeds defines the monomer, dimer, and trimer superlattice, while its magnetic orientation positive or negative the parallel (PM) or antiparallel magnetization (AM) superlattice configuration. The transfer matrix method and the Landauer-Büttiker formalism are employed to obtain the transmission and transport properties, respectively. We find multiplication of TMR peaks in staircase fashion according to the number of B seeds in the superlattice unit cell. This multiplication is related to the multiplication of the minibands which reflects as multiplication of the descending envelopes of the conductance. We also find well-defined polarization states for both PM and AM by adjusting asymmetrically the width and height of the barrier-well in seeds A and B.

12.
Ther Deliv ; 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38469701

RESUMO

Aim: This study explores chia oil, rich in ω-3 fatty acids and nutraceutical components, as a potential remedy for diseases, especially those linked to inflammation and cancer. Methods/materials: A chia oil-based nanoemulsion, developed through single emulsification, underwent comprehensive analysis using various techniques. In vitro and in vivo assays, including macrophage polarization, nitrite and cytokine production, cellular uptake and biodistribution, were conducted to assess the anti-inflammatory efficacy. Results & conclusion: Results reveal that the chia nanoemulsion significantly inhibits inflammation, outperforming pure oil with twice the efficacy. Enhanced uptake by macrophage-like cells and substantial accumulation in key organs indicate its potential as an economical and effective anti-inflammatory nanodrug, addressing global economic and health impacts of inflammation-related diseases.

13.
Inflammopharmacology ; 32(2): 1239-1252, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38472616

RESUMO

BACKGROUND: Osteoarthritis (OA) is a chronic disease that may lead to joint structure degeneration, cartilage destruction, osteophyte formation, subchondral bone disruption, and pain. In this scenario, a higher proportion of the proinflammatory macrophage type 1 (M1) than the anti-inflammatory macrophage type 2 (M2) could be highlighted as a hallmark of OA progression. The balance between these two macrophage types emerges as a new therapeutic target in OA. This study aimed to evaluate the analgesia and macrophage profile in the treatment of experimental osteoarthritis (EOA) with systemic dimethyl fumarate (DMF) or local intra-articular monomethyl fumarate (MMF). RESULTS: DMF via gavage or MMF via intra-articular in the right knee of EOA rats showed improvements in gait parameters and the nociceptive recovery of the mechanical threshold assessment by adapted electronic von Frey treatment on the twenty-first day (long-lasting phase). DMF treatment decreased proinflammatory TNF-α while increasing anti-inflammatory IL-10 cytokines from the macerated capsule on the fifth day (inflammatory phase). MMF treatment showed joint capsule mRNA extraction downregulating iNOS and TNF-α gene expression while upregulating IL-10 and MCP-1. However, CD206 was not significant but higher than untreated EOA rats' joints on the seventh day (inflammatory phase). CONCLUSIONS: Our studies with EOA model induced by MIA suggest a new perspective for human treatment committed with OA based on macrophage polarization as a therapeutic target, switching the proinflammatory profile M1 to the anti-inflammatory profile M2 with DMF systematic or by MMF locally treatment according to the OA severity.


Assuntos
Fumaratos , Interleucina-10 , Osteoartrite , Humanos , Ratos , Animais , Fator de Necrose Tumoral alfa , Osteoartrite/metabolismo , Dor/tratamento farmacológico , Fumarato de Dimetilo , Macrófagos/metabolismo , Anti-Inflamatórios/uso terapêutico
14.
Braz. j. med. biol. res ; 57: e13235, fev.2024. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1550145

RESUMO

Abstract The imbalance between pro-inflammatory M1 and anti-inflammatory M2 macrophages plays a critical role in the pathogenesis of sepsis-induced acute lung injury (ALI). Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) may modulate macrophage polarization toward the M2 phenotype by altering mitochondrial activity. This study aimed to investigate the role of the PGC-1α agonist pioglitazone (PGZ) in modulating sepsis-induced ALI. A mouse model of sepsis-induced ALI was established using cecal ligation and puncture (CLP). An in vitro model was created by stimulating MH-S cells with lipopolysaccharide (LPS). qRT-PCR was used to measure mRNA levels of M1 markers iNOS and MHC-II and M2 markers Arg1 and CD206 to evaluate macrophage polarization. Western blotting detected expression of peroxisome proliferator-activated receptor gamma (PPARγ) PGC-1α, and mitochondrial biogenesis proteins NRF1, NRF2, and mtTFA. To assess mitochondrial content and function, reactive oxygen species levels were detected by dihydroethidium staining, and mitochondrial DNA copy number was measured by qRT-PCR. In the CLP-induced ALI mouse model, lung tissues exhibited reduced PGC-1α expression. PGZ treatment rescued PGC-1α expression and alleviated lung injury, as evidenced by decreased lung wet-to-dry weight ratio, pro-inflammatory cytokine secretion (tumor necrosis factor-α, interleukin-1β, interleukin-6), and enhanced M2 macrophage polarization. Mechanistic investigations revealed that PGZ activated the PPARγ/PGC-1α/mitochondrial protection pathway to prevent sepsis-induced ALI by inhibiting M1 macrophage polarization. These results may provide new insights and evidence for developing PGZ as a potential ALI therapy.

15.
Sci Justice ; 64(1): 1-8, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38182305

RESUMO

In this article we have explored the use of Mueller polarimetry for the simultaneous and non-destructive latent fingerprint development and background elimination. This proposal not only expands previously reported uses of the polarization state of light for fingerprint development, but offers some advantages. Samples of a few donors, taken on different heavily back grounded substrates, were measured and processed. Several strategies for background removal were applied. The results are very promising, since the background was successfully erased in all cases and the quality of the developed fingerprints was excellent for most substrates and donors. Considering that the method is non-destructive and that the proposed measurement instrument is inexpensive and portable the method could be tried in real cases with no risk for the evidence. In addition, the success of the procedure for background removal raises the possibility of exploring if it would work for the enhancement of fingerprints developed with other methods.

16.
Biochem Biophys Res Commun ; 696: 149455, 2024 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-38176247

RESUMO

Macrophages switch among different activation phenotypes according to distinct environmental stimuli, varying from pro-inflammatory (M1) to alternative (also named resolutive; M2) activation forms. M1-and M2-activated macrophages represent the two extremes of the activation spectrum involving multiple species, which vary in terms of function and the cytokines secreted. The consensus is that molecular characterization of the distinct macrophage population and the signals driving their activation will help in explaining disease etiology and formulating therapies. For instance, myeloid cells residing in the tumor microenvironment are key players in tumor progression and usually display an M2-like phenotype, which help tumor cells to evade local inflammatory processes. Therefore, these specific cells have been proposed as targets for tumor therapies by changing their activation profile. Furthermore, M2 polarized macrophages are phagocytic cells promoting tissue repair and wound healing and are therefore potential targets to treat different diseases. We have already shown that clotrimazole (CTZ) decreases tumor cell viability and thus tumor growth. The mechanism by which CTZ exerts its effects remains to be determined, but this drug is an inhibitor of the PI3K/AKT/mTOR pathway. In this study, we show that CTZ downregulated M2-activation markers in macrophages polarized to the M2 profile. This effect occurred without interfering with the expression of M1-polarized markers or pro-inflammatory cytokines and signaling. Moreover, CTZ suppressed NFkB pathway intermediates and disrupted PI3K/AKT/mTOR signaling. We concluded that CTZ reverses macrophage M2 polarization by disrupting the PI3K/AKT/mTOR pathway, which results in the suppression of NFkB induction of M2 polarization. In addition, we find that CTZ represents a promising therapeutic tool as an antitumor agent.


Assuntos
Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Clotrimazol/farmacologia , Serina-Treonina Quinases TOR/metabolismo , Macrófagos/metabolismo , Citocinas/metabolismo , NF-kappa B/metabolismo , Ativação de Macrófagos
17.
Int Immunol ; 36(3): 111-128, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38066638

RESUMO

Nurr1 is a member of the orphan nuclear receptor family NR4A (nuclear receptor subfamily 4 group A) that modulates inflammation in several cell lineages, both positively and negatively. Macrophages are key regulators of inflammatory responses, yet information about the role of Nurr1 in human macrophages is scarce. Here we examined Nurr1 expression and activity in steady state and activated human macrophages. Pro- and anti-inflammatory macrophages were generated in vitro by culture of blood monocytes with granulocyte/macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF), respectively. Nurr1 expression was predominant in macrophages with the pro-inflammatory phenotype. Nurr1 activation with the agonists 1,1-bis(3'-indolyl)-1-(p-chlorophenyl) methane (C-DIM12) or isoxazolo-pyridinone 7e (IP7e) did not globally modify the polarization status of pro-inflammatory macrophages, but they decreased their production of TNF, IL-1ß, IL-6, IL-8, IL-12 p40, CCL2, IFN-ß, and reactive oxygen species, with variable potencies. Conversely, Nurr1 deficient macrophages increased the expression of transcripts encoding inflammatory mediators, particularly that of IL6, IFNB1, and CCL2. Mechanistically, endogenous Nurr1 interacted with NF-κB p65 in basal conditions and upon lipopolysaccharide (LPS)-mediated activation. C-DIM12 stabilized those complexes in cells exposed to LPS and concurrently decreased NF-κB transcriptional activity and p65 nuclear translocation. Expression of high levels of Nurr1 was associated with a subset of dermal macrophages that display enhanced levels of TNF and lower expression of the anti-inflammatory marker CD163L1 in skin lesions from patients with bullous pemphigoid (BP), a chronic inflammatory autoimmune blistering disorder. These results suggest that Nurr1 expression is linked with the pro-inflammatory phenotype of human macrophages, both in vivo and in vitro, where it may constitute a brake to attenuate the synthesis of inflammatory mediators.


Assuntos
Fator Estimulador de Colônias de Macrófagos , NF-kappa B , Humanos , NF-kappa B/metabolismo , Fator Estimulador de Colônias de Macrófagos/metabolismo , Lipopolissacarídeos/farmacologia , Macrófagos , Membro 2 do Grupo A da Subfamília 4 de Receptores Nucleares/genética , Membro 2 do Grupo A da Subfamília 4 de Receptores Nucleares/metabolismo , Receptores Citoplasmáticos e Nucleares/metabolismo , Inflamação/metabolismo , Mediadores da Inflamação/metabolismo , Anti-Inflamatórios/metabolismo
18.
Cancers (Basel) ; 15(24)2023 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-38136358

RESUMO

High-risk human papillomavirus (HPV) infection is one of the leading causes of oropharyngeal squamous cell carcinoma (OPSCC), while the correlation between HPV and oral squamous cell carcinoma (OSCC) remains controversial. The inflammatory infiltrate involved in these epithelial neoplasms differs based on their association with HPV. HPV- tumors show higher tumor-associated neutrophil (TAN) infiltration. It is believed that TANs can play a dual role in cancer by exerting either anti-tumorigenic or pro-tumorigenic effects. However, the impact of HPV status on neutrophil polarization remains unknown. Therefore, this study aimed to investigate the effect of OSCC cells, both HPV- and HPV16+, on the functional phenotype of neutrophils. Peripheral blood neutrophils were stimulated with supernatants from OSCC cell lines and non-tumorigenic HaCaT keratinocytes transduced with HPV16 E6/E7 oncogenes. Subsequently, cytokine production, cell viability, metabolism, expression of degranulation markers, and PD-L1 expression were evaluated. Our findings demonstrate that in contrast to UPCI:SCC154 (HPV+ OSCC) cells, the SCC-9 (HPV- OSCC) cell line induced a highly activated functional state in neutrophils, which is potentially associated with a pro-tumorigenic effect. The HaCaT 16-E7 supernatant only stimulated the activation of some neutrophil functions. Understanding the complex interplay between neutrophils and their microenvironment has the potential to identify TANs as viable therapeutic targets.

19.
Entramado ; 19(2)dic. 2023.
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1534435

RESUMO

Paralelo a las transformaciones políticas y culturales a nivel mundial en los años veinte, se inició en Colombia, en este mismo decenio, un ambiente de polarización política, la cual tuvo un nuevo ingrediente en la renovada disputa entre los partidos tradicionales: el pánico rojo. El pánico rojo fue una estrategia de permanente campaña de desinformación que los diarios locales y nacionales llevaron a cabo con claros intereses políticos. El propósito de este artículo es analizar este temor al comunismo en el contexto de la confrontación política en las décadas de 1930-1940 en Santander: Esto permitirá reconocer qué grupos, y desde qué publicaciones periódicas, se asumieron como grupos de izquierda. Además, se busca identificar quiénes fueron tachados de comunistas y cómo se utilizó esta arma discursiva a partir del miedo, para polarizar aún más la política y exacerbar la violencia. Para llevar a cabo este análisis, se examinarán tres publicaciones periódicas de diferentes espectros políticos: "El Deber", "Vanguardia Liberal" y "Tribuna Liberal". Se prestará especial atención al uso cambiante que estos diarios hicieron del anticomunismo en diferentes coyunturas políticas.


Parallel to the worldwide political and cultural transformations in the twenties, an environment of political polarization began in Colombia in this same decade, which had a new ingredient in the renewed dispute between the traditional parties: the red panic. The red panic was a permanent disinformation campaign strategy carried out by local and national newspapers with clear political interests. The purpose of this article is to analyze this fear of communism in the context of the political confrontation in the I930-I940s in Santander This will make it possible to recognize which groups, and from which periodicals, assumed themselves to be left-wing groups. In addition, it seeks to identify who was branded as communists and how this discursive weapon was used based on fear, to further polarize politics and exacerbate violence. To carry out this analysis, three periodicals from different political spectrums will be examined: "El Deber", "Vanguardia Liberal" and "Tribuna Liberal". Special attention will be paid to the changing use that these newspapers made of anti-communism in different political situations.


Paralelamente às transformações políticas e culturais globais da década de 1920, nessa mesma década iniciou-se um clima de polarização política na Colômbia, que teve um novo ingrediente na renovada disputa entre os partidos tradicionais: o pânico vermelho. O pânico vermelho foi uma estratégia de campanha de desinformação contínua realizada por jornais locais e nacionais com claros interesses políticos. O objetivo deste artigo é analisar esse medo do comunismo no contexto do confronto político dos anos 1930-1940 em Santander. Isso permitirá reconhecer quais grupos e quais jornais se assumiram como grupos de esquerda. Além disso, busca identificar quem foi tachado de comunista e como essa arma discursiva baseada no medo foi utilizada para polarizar ainda mais a política e exacerbar a violência. Para realizar esta análise, serão examinados três jornais de diferentes espectros políticos: "El Deber", "Vanguardia Liberal" e "Tribuna Liberal". Será dada especial atenção à evolução do uso que estes jornais fizeram do anticomunismo em diferentes situações políticas.

20.
Int J Mol Sci ; 24(21)2023 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-37958514

RESUMO

The complex interplay between dietary factors, inflammation, and macrophage polarization is pivotal in the pathogenesis and progression of chronic liver diseases (CLDs). Omega-3 fatty acids (FAs) have brought in attention due to their potential to modulate inflammation and exert protective effects in various pathological conditions. Omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have shown promise in mitigating inflammation and enhancing the resolution of inflammatory responses. They influence the M1/M2 macrophage phenotype balance, promoting a shift towards the M2 anti-inflammatory phenotype. Specialized pro-resolving mediators (SPMs), such as resolvins (Rvs), protectins (PDs), and maresins (MaRs), have emerged as potent regulators of inflammation and macrophage polarization. They show anti-inflammatory and pro-resolving properties, by modulating the expression of cytokines, facilitate the phagocytosis of apoptotic cells, and promote tissue repair. MaR1, in particular, has demonstrated significant hepatoprotective effects by promoting M2 macrophage polarization, reducing oxidative stress, and inhibiting key inflammatory pathways such as NF-κB. In the context of CLDs, such as nonalcoholic fatty liver disease (NAFLD) and cirrhosis, omega-3s and their SPMs have shown promise in attenuating liver injury, promoting tissue regeneration, and modulating macrophage phenotypes. The aim of this article was to analyze the emerging role of omega-3 FAs and their SPMs in the context of macrophage polarization, with special interest in the mechanisms underlying their effects and their interactions with other cell types within the liver microenvironment, focused on CLDs and the development of novel therapeutic strategies.


Assuntos
Ácidos Graxos Ômega-3 , Hepatopatias , Humanos , Ácidos Graxos Ômega-3/farmacologia , Ácidos Graxos Ômega-3/metabolismo , Macrófagos/metabolismo , Inflamação/metabolismo , Ácidos Docosa-Hexaenoicos/metabolismo , Anti-Inflamatórios/uso terapêutico , Hepatopatias/metabolismo , Fenótipo , Mediadores da Inflamação/metabolismo
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