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1.
J Forensic Odontostomatol ; 42(2): 60-75, 2024 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-39244767

RESUMO

Estimating the post-mortem interval (PMI) of human remains based on the histomorphology of dental pulp parameters is promising, but available evidence is scarce and sometimes contradictory without a scientific model. The aim of the study is to characterise the histomorphological changes of dental pulp associated with the decomposition of human remains by a qualitative and quantitative approach. The main aim is to establish a correlation based on post-mortem (PM) dental pulp histomorphology and the PMI, and whether pulp degradation could be an available medico-legal tool for PMI estimation beyond the first week after death (late PMI). The eligible sample consisted of 27 sound teeth from 16 healthy patients aged 16 to 72 years due to orthodontic or oral surgery treatment, to create PMI's simulating the death of the subject as the time elapsed from tooth avulsion. Data collected from patients (sex, date of birth, tooth position, date and hour of the avulsion, date and hour of pulp extraction) were anonymised in accordance with the requirements of Faculty of Dental Medicine of the University of Lisbon. The sample was divided into 9 groups of 3 teeth according to different PMI sets from T0 (baseline) up to 2 weeks (T0, 7, 12, 24, 36, 48, and 72 hours, 1 and 2 weeks). All the dental samples were stored at room temperature up to the time of pulp extraction and then prepared with haematoxylin and eosin stain. High-resolution microscopy was performed to obtain histological images. An operator performed the qualitative evaluation of blood vessels, collagen fibres, and the extra-cellular matrix (ECM) in PM pulps and measured the variation in cells/nuclei density by counting 6 different ROIs (Regions of Interest) for each pulp manually and automatically (quantitative analysis). Qualitative results showed that the degeneration of dental pulp appears 7 hours after death but histological changes in vessels, fibres, and ECM in PM dental pulp are characterised by high variability, consequently it is not possible to generalise the results for early PMIs. Quantitative measurements proved that cell count cannot be standardised due to the presence of superimposed layers of cells and nuclei fragmentation. Odontoblasts did not demonstrate evidence of cellular or nuclear lysis up to 14 PM suggesting their applicability in late PMIs. Future research will focus on late PMIs and different techniques of tooth preparation.


Assuntos
Polpa Dentária , Mudanças Depois da Morte , Humanos , Polpa Dentária/patologia , Adulto , Feminino , Adolescente , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Idoso , Odontologia Legal/métodos , Odontoblastos/patologia , Microscopia , Colágeno/análise
2.
Microorganisms ; 12(9)2024 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-39338560

RESUMO

Human zoonotic visceral leishmaniasis (ZVL) and canine leishmaniasis (CanL) constitute a major public and veterinary health concern and are both caused by the infection with the protozoan parasite Leishmania infantum. One of the main target organs in CanL is the liver. This complex organ, composed of various highly specialized cell types, has garnered significant attention from the scientific community as a crucial player in innate immune functions. In the context of CanL, liver infection by parasites and the host immune response generated strongly influence the disease outcome. Thus, taking advantage of a co-culture system involving canine hepatocytes and L. infantum-infected autologous Kupffer cells (KCs), allowing cell-to-cell interaction, the current report aims to shed light on the hepatocyte-KCs immune interaction. The co-culture of infected KCs with hepatocytes revealed a vital role of these cells in the activation of a local immune response against L. infantum parasites. Although KCs alone can be immunologically silenced by L. infantum infection, the cell-to-cell interaction with hepatocytes in co-culture can lead to local immune activation. In co-culture it was observed gene expression increased the number of innate immune receptors, specifically cell membrane TLR2 and cytoplasmatic NOD1 along with high TNF-α generation. Altogether, these results suggest that the immune response generated in co-culture could induce the recruitment of other circulating cells to contain and contribute to the resolution of the infection in the liver. This work also enhances our understanding of the liver as a vital organ in innate immunity within the context of CanL.

3.
Nefrologia (Engl Ed) ; 44(3): 344-353, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39002995

RESUMO

INTRODUCTION AND OBJECTIVES: Functional and durable vascular access is needed for adequate hemodialysis. Arteriovenous fistula is preferred over prosthetic grafts or central venous catheters, but it is associated with high rates of primary failure and maturation failure. Preoperative mapping of arm vessels with color Doppler ultrasound (CDU) has been shown to be helpful in achieving better short and long-term outcomes. Unfortunately, is more time-consuming than a physical examination and requires an experienced examiner and special equipment; some authors defend that CDU should not be part of the routine preoperative assessment. We reported our experience in preoperative vessel mapping using color Doppler ultrasound to purpose a vascular access to the surgical team, surveillance of vascular access, and evaluation of main outcomes (primary failure, maturation failure, and patency). METHODS: This is a single-center retrospective study that includes patients who attended a specific appointment for vascular access planning consultation between January 2019 and December 2021. A nephrologist performed the physical exam and vascular mapping and proposed to the vascular surgeon team a specific type and location of vascular access. Patients were followed until one month after the first hemodialysis through functioning vascular access. RESULTS: In this study, 167 patients were evaluated (114 incident patients - chronic kidney disease stage 4 or 5 - and 53 prevalent patients - under hemodialysis through central venous catheter). The vascular accesses proposed by nephrologist were radial-cephalic arteriovenous fistula in 70 patients (41.9%), brachio-cephalic arteriovenous fistula in 50 patients (29.9%), brachio-basilic arteriovenous fistula in 34 patients (20.4%), arteriovenous graft in 8 patients (4.8%) and central venous catheter in 2 patients (1.2%). Vascular access was constructed in 141 patients: distal arteriovenous fistula in 57 patients (40.4%), brachio-cephalic arteriovenous fistula in 54 patients (38.3%), brachio-basilic AVF in 27 patients (19.1%), and arteriovenous graft in 3 patients (2.1%). The created access corresponds to the proposed access in 129 patients (91.5%). Twenty-two (15.6%) primary failures were registered. Distal arteriovenous fistulas and diabetes mellitus were associated with a higher risk of primary failure (OR=3.929 (1.485-10.392), p=0.004; OR=3.867 (1.235-12.113), p=0.014, respectively). The incidence of maturation failure at eight weeks was 4.8%. The primary patency at 6, 12 and 24 months was 76.3%, 70.4% and 49.2%. Primary assisted patency was 84.8% at 6 and 12 months and 81.3% at 24 months. CONCLUSIONS: This study demonstrates that the study of the entire vascular territory performed with color Doppler ultrasound, within a multidisciplinary team of nephrologists and vascular surgeons, is associated with high rates of autologous access and very low rates of primary failure and maturation failure (almost unprecedented in the literature).


Assuntos
Derivação Arteriovenosa Cirúrgica , Equipe de Assistência ao Paciente , Diálise Renal , Humanos , Diálise Renal/métodos , Derivação Arteriovenosa Cirúrgica/métodos , Feminino , Masculino , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , Ultrassonografia Doppler em Cores , Cuidados Pré-Operatórios/métodos , Grau de Desobstrução Vascular
4.
Chem Biol Interact ; 399: 111156, 2024 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-39029856

RESUMO

Leishmaniases, caused by Leishmania parasites, are widespread and pose significant health risks globally. Visceral leishmaniasis (VL) is particularly prevalent in Brazil, with high morbidity and mortality rates. Traditional treatments, such as pentavalent antimonials, have limitations due to toxicity and resistance. Therefore, exploring new compounds like lectins is crucial. Concanavalin A (ConA) has shown promise in inhibiting Leishmania growth. This study aimed to evaluate its leishmanicidal effect on L. infantum promastigotes and understand its mechanism of action. In vitro tests demonstrated inhibition of promastigote growth when treated with ConA, with IC50 values ranging from 3 to 5 µM over 24-72 h. This study suggests that ConA interacts with L. infantum glycans. Additionally, ConA caused damage to the membrane integrity of parasites and induced ROS production, contributing to parasite death. Scanning electron microscopy confirmed morphological alterations in treated promastigotes. ConA combined with the amphotericin B (AmB) showed synergistic effects, reducing the required dose of AmB, and potentially mitigating its toxicity. ConA demonstrated no cytotoxic effects on macrophages, instead stimulating their proliferation. These findings reinforce that lectin exhibits promising leishmanicidal activity against L. infantum promastigotes, making ConA a potential candidate for leishmaniasis treatment.


Assuntos
Antiprotozoários , Canavalia , Concanavalina A , Leishmania infantum , Leishmania infantum/efeitos dos fármacos , Concanavalina A/farmacologia , Animais , Antiprotozoários/farmacologia , Antiprotozoários/química , Sementes/química , Espécies Reativas de Oxigênio/metabolismo , Camundongos , Anfotericina B/farmacologia , Lectinas/farmacologia , Lectinas/química , Lectinas/metabolismo , Lectinas de Plantas/farmacologia , Lectinas de Plantas/química , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Macrófagos/parasitologia
5.
Microorganisms ; 12(5)2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38792775

RESUMO

The causative agent of Chagas disease is Trypanosoma cruzi, which is widely distributed throughout the South American continent and extends into North America. Its occurrence in bats is poorly described and may impact the disease's maintenance and epidemiology. The aim of this study was to detect the agent by PCR assays targeting kDNA and nuclear DNA in the organs of 203 urban bats and rural vampire bats from the Brazilian Atlantic Forest, São Paulo state, during the pandemic period from 2020 to 2022. In total, 6 of the 203 bats (2.97%) were positive for T. cruzi. Infection was detected in 2% (2/101) of Desmodus rotundus, 33% (1/3) of Nyctinomops laticaudatus, 25% (1/4) of Artibeus lituratus, 4% (1/24) of Eumops glaucinus and in 2% (1/41) of Molossus molossus. The gene sequences obtained were assessed for quality and deposited in a public repository. Fruit bats were statistically associated with positivity for T. cruzi. To our knowledge, this study detected T. cruzi for the first time in bats from São Paulo state and in N. laticaudatus and E. glaucinus species.

7.
Int J Mol Sci ; 25(7)2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38612650

RESUMO

Chagas disease (CD) is a vector-borne Neglected Zoonotic Disease (NZD) caused by a flagellate protozoan, Trypanosoma cruzi, that affects various mammalian species across America, including humans and domestic animals. However, due to an increase in population movements and new routes of transmission, T. cruzi infection is presently considered a worldwide health concern, no longer restricted to endemic countries. Dogs play a major role in the domestic cycle by acting very efficiently as reservoirs and allowing the perpetuation of parasite transmission in endemic areas. Despite the significant progress made in recent years, still there is no vaccine against human and animal disease, there are few drugs available for the treatment of human CD, and there is no standard protocol for the treatment of canine CD. In this review, we highlight human and canine Chagas Disease in its different dimensions and interconnections. Dogs, which are considered to be the most important peridomestic reservoir and sentinel for the transmission of T. cruzi infection in a community, develop CD that is clinically similar to human CD. Therefore, an integrative approach, based on the One Health concept, bringing together the advances in genomics, immunology, and epidemiology can lead to the effective development of vaccines, new treatments, and innovative control strategies to tackle CD.


Assuntos
Doenças dos Animais , Doença de Chagas , Doenças do Cão , Trypanosoma cruzi , Humanos , Cães , Animais , Doença de Chagas/epidemiologia , Doença de Chagas/veterinária , Animais Domésticos , Doenças do Cão/epidemiologia , Mamíferos
8.
Cells ; 13(5)2024 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-38474410

RESUMO

Dendritic cells (DCs) capture pathogens and process antigens, playing a crucial role in activating naïve T cells, bridging the gap between innate and acquired immunity. However, little is known about DC activation when facing Leishmania parasites. Thus, this study investigates in vitro activity of canine peripheral blood-derived DCs (moDCs) exposed to L. infantum and L. amazonensis parasites and their extracellular vesicles (EVs). L. infantum increased toll-like receptor 4 gene expression in synergy with nuclear factor κB activation and the generation of pro-inflammatory cytokines. This parasite also induced the expression of class II molecules of major histocompatibility complex (MHC) and upregulated co-stimulatory molecule CD86, which, together with the release of chemokine CXCL16, can attract and help in T lymphocyte activation. In contrast, L. amazonensis induced moDCs to generate a mix of pro- and anti-inflammatory cytokines, indicating that this parasite can establish a different immune relationship with DCs. EVs promoted moDCs to express class I MHC associated with the upregulation of co-stimulatory molecules and the release of CXCL16, suggesting that EVs can modulate moDCs to attract cytotoxic CD8+ T cells. Thus, these parasites and their EVs can shape DC activation. A detailed understanding of DC activation may open new avenues for the development of advanced leishmaniasis control strategies.


Assuntos
Leishmania , Animais , Cães , Linfócitos T CD8-Positivos , Células Dendríticas , Adjuvantes Imunológicos/metabolismo , Citocinas/metabolismo , Ativação Linfocitária
9.
Vet Parasitol Reg Stud Reports ; 47: 100964, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38199683

RESUMO

Cryptosporidium is a protozoan parasite with worldwide distribution, infecting a wide range of hosts with some zoonotic species. Calves have been identified as one of the most common reservoirs of this parasite. However, little is known about the genetics of Cryptosporidium in calves in Portugal. This study aimed to molecularly characterize infections of Cryptosporidium in pre-weaned calves from the Lisbon and Tagus Valley (LTV) in Portugal. Fifty-two samples were collected from calves from eight dairy and two beef farms in LTV, Portugal. Cryptosporidium oocysts were detected by Modified Ziehl-Neelsen staining (MZN) and direct immunofluorescent assay (DFA). MZN and DFA revealed the presence of Cryptosporidium oocysts in 40.4% (21/52) and 67.3% (35/52) samples, respectively. Positive samples were analyzed by PCR-RFLP of the 18 s rRNA gene for species identification. DNA amplification of the 18S rRNA gene was successful for 88.6% (31/35) of samples. Cryptosporidium parvum was identified in 96.8% (30/31) of the samples, and from one sample Cryptosporidium bovis was identified. Cryptosporidium parvum positive samples were subtyped by sequencing the PCR product of a partial fragment of the 60 kDa glycoprotein (gp60) gene. Subtype analysis of the C. parvum isolates revealed that all isolates belonged to subtype family IIa. Four subtypes were recognized within this subtype family, including the hyper-transmissible IIaA15G2R1 subtype that is the most frequently reported worldwide (27/30), IIaA14G2R1 (1/30), IIaA16G2R1 (1/30) and IIaA19G2R1 (1/30). To our knowledge, this is the first report of C. bovis, and C. parvum subtypes IIaA14G2R1 and IIaA19G2R1 in cattle in LTV, Portugal. The presence of the zoonotic C. parvum subtype in this study suggests that pre-weaned calves are likely to be a significant reservoir of zoonotic C. parvum, highlighting the importance of animal-to-human infection transmission risk. Further molecular studies are required to better understand the epidemiology of cryptosporidiosis in Portugal.


Assuntos
Doenças dos Bovinos , Criptosporidiose , Cryptosporidium parvum , Cryptosporidium , Humanos , Animais , Bovinos , Cryptosporidium/genética , Portugal/epidemiologia , Criptosporidiose/epidemiologia , Cryptosporidium parvum/genética , Meio Ambiente , Oocistos , Doenças dos Bovinos/epidemiologia
10.
Psychol Rep ; : 332941241226685, 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38232373

RESUMO

Background: Neuroscience research methods contribute to the understanding of the underlying neural impairments associated with psychopathology. Previous research suggested that impairments in Default Mode Network, Fronto-Parietal Executive Network, Amygdaloid-Hippocampal Memory Network, and Attentional Salience Network are present in different psychopathological symptoms. However, a self-report measure based on this evidence is lacking. Aims: Therefore, the present study describes the development and preliminary psychometric study of the Neural Network Symptomatology Inventory (NNSI). Method: Two different samples were recruited (sample 1: N = 214, Mage = 21.0, SD = 7.10; sample 2: N = 194, Mage = 21.5, SD = 8.41) and responded to self-report instruments in a cross-sectional design. Standard methodologies to scale development and psychometric study were applied: Item development, Exploratory (EFA), Confirmatory Factor Analysis (CFA), and Pearson correlations. Results: EFA and CFA suggested a 4-factor model with adequate goodness-of-fit indices (χ2(449) = 808,9841, TLI = .89, CFI = .92, RMSEA = .048 (.042-.053). All NNSI subscales correlated positively with psychopathological domains and correlated negatively with psychological well-being. Conclusions: This preliminary study suggests that NNSI may be a valid instrument to assess symptomatology associated with complex neural network impairments. Nevertheless, further research is required to deepen and improve NNSI psychometric characteristics.

11.
Artigo em Inglês | MEDLINE | ID: mdl-38008834

RESUMO

Tingui biochar (TB) activated with potassium hydroxide (TB-KOH) was synthesized in the present study. The adsorption capacity of TB-KOH was evaluated for the removal of acetaminophen and caffeine in monocomponent and bicomponent solutions. As a result, the study of the TB-KOH characterization as well as the adsorption kinetics, isotherm, thermodynamics, and a suggestion of the global adsorption mechanism are presented. TB-KOH was characterized through physical-chemical analysis to understand its surface morphology and how it contributes to the adsorption of these drugs. Furthermore, modelling using advanced statistical physical models was performed to describe how acetaminophen and caffeine molecules are adsorbed in the active sites of TB-KOH. Through the characterizations, it was observed that the activation with KOH contributed to the development of porosity and functional groups (-OH, C-O, and C = O) on the surface of TB. The monocomponent adsorption equilibrium was reached in 90 min with a maximum adsorption capacity of 424.7 and 350.8 mg g-1 for acetaminophen and caffeine, respectively. For the bicomponent solution adsorption, the maximum adsorption capacity was 199.4 and 297.5 mg g-1 for acetaminophen and caffeine, respectively. The isotherm data was best fitted to the Sips model, and the thermodynamic study indicated that acetaminophen removal was endothermic, while caffeine removal was exothermic. The mechanism of adsorption of acetaminophen and caffeine by TB-KOH was described by the involvement of hydrogen bonds and π-π interactions between the surface of TB-KOH and the molecules of the contaminants.

12.
Front Oncol ; 13: 1264287, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37795454

RESUMO

Salivary gland cancers (SGCs) are rare, accounting for less than 5% of all malignancies of the head and neck region, and are morphologically heterogeneous. The diagnosis is mainly based on histology, with the complementary aid of molecular profiling, which is helpful in recognizing some poorly differentiated, borderline, or atypical lesions. Instrumental imaging defines the diagnosis, representing a remarkable tool in the treatment plan. Ultrasound and magnetic resonance are the most common procedures used to describe the primary tumour. The treatment of SGCs is multimodal and consists of surgery, radiotherapy, and systemic therapy; each treatment plan is, however, featured on the patient and disease's characteristics. On 24 June 2022, in the meeting "Current management and future challenges in salivary gland cancers" many experts in this field discussed the state of the art of SGCs research, the future challenges and developments. After the meeting, the same pool of experts maintained close contact to keep these data further updated in the conference proceedings presented here. This review collects the insights and suggestions that emerged from the discussion during and after the meeting per se.

13.
Parasit Vectors ; 16(1): 384, 2023 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-37880680

RESUMO

BACKGROUND: The ticks Ixodes ricinus and Dermacentor reticulatus are two of the most important vectors in Europe. Climate niche modelling has been used in many studies to attempt to explain their distribution and to predict changes under a range of climate change scenarios. The aim of this study was to assess the ability of different climate niche modelling approaches to explain the known distribution of I. ricinus and D. reticulatus in Europe. METHODS: A series of climate niche models, using different combinations of input data, were constructed and assessed. Species occurrence records obtained from systematic literature searches and Global Biodiversity Information Facility data were thinned to different degrees to remove sampling spatial bias. Four sources of climate data were used: bioclimatic variables, WorldClim, TerraClimate and MODIS satellite-derived data. Eight different model training extents were examined and three modelling frameworks were used: maximum entropy, generalised additive models and random forest models. The results were validated through internal cross-validation, comparison with an external independent dataset and expert opinion. RESULTS: The performance metrics and predictive ability of the different modelling approaches varied significantly within and between each species. Different combinations were better able to define the distribution of each of the two species. However, no single approach was considered fully able to capture the known distribution of the species. When considering the mean of the performance metrics of internal and external validation, 24 models for I. ricinus and 11 models for D. reticulatus of the 96 constructed were considered adequate according to the following criteria: area under the receiver-operating characteristic curve > 0.7; true skill statistic > 0.4; Miller's calibration slope 0.25 above or below 1; Boyce index > 0.9; omission rate < 0.15. CONCLUSIONS: This comprehensive analysis suggests that there is no single 'best practice' climate modelling approach to account for the distribution of these tick species. This has important implications for attempts to predict climate-mediated impacts on future tick distribution. It is suggested here that climate variables alone are not sufficient; habitat type, host availability and anthropogenic impacts, not included in current modelling approaches, could contribute to determining tick presence or absence at the local or regional scale.


Assuntos
Dermacentor , Ixodes , Animais , Biodiversidade , Ecossistema , Europa (Continente)
14.
Psychol Rep ; : 332941231202016, 2023 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-37732823

RESUMO

Personality theory based on affective neuroscience research suggests the presence of seven affective neurobiological systems. These dimensions have been identified using psychometric instruments such as the Affective Neuroscience Personality Scales (ANPS) and its brief version known as the Brief Affective Neuroscience Personality Scales (BANPS). Despite being a psychometric valid instrument, the BANPS was not adapted to European Portuguese. This study describes a psychometric analysis of the BANPS in a Portuguese population sample. A European Portuguese-speaking sample was recruited (N = 355, Mage = 27.31, DP = 12.75). Confirmatory factor analysis (CFA) was used to confirm the BANPS factorial structure. Pearson correlations were used to explore convergent validity with self-reports for psychological distress and psychopathology. Six factor model was confirmed with adequate goodness-of-fit indices (χ2(449) = 808,9841, TLI = .90, CFI = .92, RMSEA = .048 (.042-.053). Non-agreeable affective systems (anger, fear, distress), correlated positively with psychological distress and symptomology, while play and care systems correlated negatively. Seek and care subscales showed the weakest psychometric properties. The original factor structure was confirmed, suggesting the BANPS may be a valid measure to assess affective behavioral traits in the Portuguese population. Further studies in clinical populations may improve the psychometric data of the BANPS.

15.
J Pathol ; 261(3): 256-268, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37565350

RESUMO

Adenoid cystic carcinoma (ACC) is a MYB-driven head and neck malignancy with high rates of local recurrence and distant metastasis and poor long-term survival. New effective targeted therapies and clinically useful biomarkers for patient stratification are needed to improve ACC patient survival. Here, we present an integrated copy number and transcriptomic analysis of ACC to identify novel driver genes and prognostic biomarkers. A total of 598 ACCs were studied. Clinical follow-up was available from 366 patients, the largest cohort analyzed to date. Copy number losses of 1p36 (70/492; 14%) and of the tumor suppressor gene PARK2 (6q26) (85/343; 25%) were prognostic biomarkers; patients with concurrent losses (n = 20) had significantly shorter overall survival (OS) than those with one or no deletions (p < 0.0001). Deletion of 1p36 independently predicted short OS in multivariate analysis (p = 0.02). Two pro-apoptotic genes, TP73 and KIF1B, were identified as putative 1p36 tumor suppressor genes whose reduced expression was associated with poor survival and increased resistance to apoptosis. PARK2 expression was markedly reduced in tumors with 6q deletions, and PARK2 knockdown increased spherogenesis and decreased apoptosis, indicating that PARK2 is a tumor suppressor in ACC. Moreover, analysis of the global gene expression pattern in 30 ACCs revealed a transcriptomic signature associated with short OS, multiple copy number alterations including 1p36 deletions, and reduced expression of TP73. Taken together, the results indicate that TP73 and PARK2 are novel putative tumor suppressor genes and potential prognostic biomarkers in ACC. Our studies provide new important insights into the pathogenesis of ACC. The results have important implications for biomarker-driven stratification of patients in clinical trials. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.


Assuntos
Carcinoma Adenoide Cístico , Neoplasias de Cabeça e Pescoço , Humanos , Carcinoma Adenoide Cístico/genética , Carcinoma Adenoide Cístico/patologia , Prognóstico , Genes Supressores de Tumor , Neoplasias de Cabeça e Pescoço/genética , Transcriptoma , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo
16.
Cells ; 12(8)2023 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-37190011

RESUMO

Leishmaniasis is a parasitic disease caused by different species of Leishmania and transmitted through the bite of sand flies vector. Macrophages (MΦ), the target cells of Leishmania parasites, are phagocytes that play a crucial role in the innate immune microbial defense and are antigen-presenting cells driving the activation of the acquired immune response. Exploring parasite-host communication may be key in restraining parasite dissemination in the host. Extracellular vesicles (EVs) constitute a group of heterogenous cell-derived membranous structures, naturally produced by all cells and with immunomodulatory potential over target cells. This study examined the immunogenic potential of EVs shed by L. shawi and L. guyanensis in MΦ activation by analyzing the dynamics of major histocompatibility complex (MHC), innate immune receptors, and cytokine generation. L. shawi and L. guyanensis EVs were incorporated by MΦ and modulated innate immune receptors, indicating that EVs cargo can be recognized by MΦ sensors. Moreover, EVs induced MΦ to generate a mix of pro- and anti-inflammatory cytokines and favored the expression of MHCI molecules, suggesting that EVs antigens can be present to T cells, activating the acquired immune response of the host. Since nano-sized vesicles can be used as vehicles of immune mediators or immunomodulatory drugs, parasitic EVs can be exploited by bioengineering approaches for the development of efficient prophylactic or therapeutic tools for leishmaniasis.


Assuntos
Micropartículas Derivadas de Células , Exossomos , Interações Hospedeiro-Patógeno , Imunomodulação , Leishmania guyanensis , Leishmania , Ativação de Macrófagos , Macrófagos , Leishmania guyanensis/imunologia , Interações Hospedeiro-Patógeno/imunologia , Leishmania/imunologia , Animais , Camundongos , Linhagem Celular , Macrófagos/imunologia , Macrófagos/parasitologia , Micropartículas Derivadas de Células/imunologia , Micropartículas Derivadas de Células/parasitologia , Exossomos/imunologia , Exossomos/parasitologia , Peptídeo Hidrolases/metabolismo , Antígenos de Histocompatibilidade Classe I/imunologia , Antígenos de Histocompatibilidade Classe II/imunologia , Citocinas/metabolismo , Imunidade Inata
17.
Appl Neuropsychol Adult ; : 1-9, 2023 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-37184438

RESUMO

Executive functions are described as a set of neurocognitive processes underlying human mental processing, while maladaptive cyclical patterns are the dysfunctional psychological elements associated with psychological distress and symptomatology that tend to be recurrent. Both psychological constructs tend to be studied by different scientific fields and with different methods which limits a coherent theoretical integration. Therefore, the present study aims to explore the relationships between executive functions and maladaptive cyclical patterns. A sample was gathered (N = 96, Mage = 20.78, SD = 4.63), and completed several self-report questionnaires along with several neuropsychological tests for the assessment of executive functions. Results showed that behavioral inhibition correlated negatively with maladaptive cyclical patterns while cognitive inflexibility correlated positively. Regression analysis showed that behavioral inhibition, psychological inflexibility, and recurring states of mind predicted emotional processing difficulties. These results emphasize previous assumptions that a difference between self-report questionnaires and behavioral tasks may limit the integrated study of psychological and neurocognitive processes.

18.
Environ Sci Pollut Res Int ; 30(30): 74820-74837, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37209332

RESUMO

Spent tire rubber-derived chars and their corresponding H3PO4 and CO2-activated chars were used as adsorbents in the recovery of Pb(II) ion and (W(VI)) oxyanion from synthetic solutions. The developed chars (both raw and activated) were thoroughly characterized to have insight about their textural and surface chemistry properties. H3PO4-activated chars presented lower surface areas than the raw chars and an acidic surface chemistry which affected the performance of these samples as they showed the lowest removals of the metallic ions. On the other hand, CO2-activated chars presented increased surface areas and increased mineral content compared to the raw chars, having presented higher uptake capacities for both Pb(II) (103-116 mg/g) and W(VI) (27-31 mg/g) ions. Cation exchange with Ca, Mg and Zn ions was appointed as a mechanism for Pb removal, as well as surface precipitation in the form of hydrocerussite (Pb3(CO3)2(OH)2). W(VI) adsorption might have been ruled by strong electrostatic attractions between the negatively charged tungstate species and the highly positively charged carbons' surface.The results shown in this work allow concluding that the valorisation of spent tire rubber through pyrolysis and the subsequent activation of the obtained chars is an alternative and a feasible option to generate adsorbent materials with a high uptake capacity of critical metallic elements.


Assuntos
Carbono , Chumbo , Borracha , Adsorção , Carbono/química , Dióxido de Carbono , Carvão Vegetal/química
19.
Pharmaceutics ; 15(5)2023 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-37242562

RESUMO

A rational design of drug delivery systems requires in-depth knowledge not only of the drug itself, in terms of physical state and molecular mobility, but also of how it is distributed among a carrier and its interactions with the host matrix. In this context, this work reports the behavior of simvastatin (SIM) loaded in mesoporous silica MCM-41 matrix (average pore diameter ~3.5 nm) accessed by a set of experimental techniques, evidencing that it exists in an amorphous state (X-ray diffraction, ssNMR, ATR-FTIR, and DSC). The most significant fraction of SIM molecules corresponds to a high thermal resistant population, as shown by thermogravimetry, and which interacts strongly with the MCM silanol groups, as revealed by ATR-FTIR analysis. These findings are supported by Molecular Dynamics (MD) simulations predicting that SIM molecules anchor to the inner pore wall through multiple hydrogen bonds. This anchored molecular fraction lacks a calorimetric and dielectric signature corresponding to a dynamically rigid population. Furthermore, differential scanning calorimetry showed a weak glass transition that is shifted to lower temperatures compared to bulk amorphous SIM. This accelerated molecular population is coherent with an in-pore fraction of molecules distinct from bulklike SIM, as highlighted by MD simulations. MCM-41 loading proved to be a suitable strategy for a long-term stabilization (at least three years) of simvastatin in the amorphous form, whose unanchored population releases at a much higher rate compared to the crystalline drug dissolution. Oppositely, the surface-attached molecules are kept entrapped inside pores even after long-term release assays.

20.
Virol J ; 20(1): 103, 2023 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-37237382

RESUMO

The European rabbit (Oryctolagus cuniculus) populations of the Iberian Peninsula have been severely affected by the emergence of the rabbit haemorrhagic disease virus (RHDV) Lagovirus europaeus/GI.2 (RHDV2/b). Bushflies and blowflies (Muscidae and Calliphoridae families, respectively) are important RHDV vectors in Oceania, but their epidemiological role is unknown in the native range of the European rabbit. In this study, scavenging flies were collected between June 2018 and February 2019 in baited traps at one site in southern Portugal, alongside a longitudinal capture-mark-recapture study of a wild European rabbit population, aiming to provide evidence of mechanical transmission of GI.2 by flies. Fly abundance, particularly from Calliphoridae and Muscidae families, peaked in October 2018 and in February 2019. By employing molecular tools, we were able to detect the presence of GI.2 in flies belonging to the families Calliphoridae, Muscidae, Fanniidae and Drosophilidae. The positive samples were detected during an RHD outbreak and absent in samples collected when no evidence of viral circulation in the local rabbit population was found. We were able to sequence a short viral genomic fragment, confirming its identity as RHDV GI.2. The results suggest that scavenging flies may act as mechanical vectors of GI.2 in the native range of the southwestern Iberian subspecies O. cuniculus algirus. Future studies should better assess their potential in the epidemiology of RHD and as a tool for monitoring viral circulation in the field.


Assuntos
Infecções por Caliciviridae , Dípteros , Vírus da Doença Hemorrágica de Coelhos , Lagovirus , Animais , Coelhos , Lagovirus/genética , Infecções por Caliciviridae/epidemiologia , Filogenia , Vírus da Doença Hemorrágica de Coelhos/genética
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