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1.
Brain Behav Evol ; 2024 Jul 24.
Article in English | MEDLINE | ID: mdl-39047702

ABSTRACT

BACKGROUND: In the best-seller book "Why zebras don't get ulcers" [1] Robert Sapolsky argues that animals do not suffer from stress-related diseases like humans, because for them stress is episodic, while humans in contrast suffer from chronic psychological stress. In particular, the idea that fish cannot experience psychological stress is still prevalent, partly due to the lack of a homologous brain area to the neocortex. However, emerging evidence suggests that teleosts can undergo psychological stress, defined as a subjective and perceptual experience of the stressor, and in recent years the underlying mechanisms started to be unveiled. SUMMARY: The occurrence of cognitive appraisal in the assessment of stressors has been demonstrated in fish, indicating that the subjective evaluation of stimulus valence and salience, rather than absolute intrinsic characteristics of the stimulus itself, play a key role in the activation of the stress response. Moreover, individual biases (i.e. cognitive bias) in the cognitive appraisal of stimuli have also been described in fish, with some individuals consistently evaluating ambiguous stimuli as positive (aka optimists) whereas other individuals (aka pessimists) appraise them as negative. As a result, optimists and pessimists show consistent differences in stress reactivity and susceptibility/ resilience to disease. Finally, social context has also been shown to modulate the response to aversive stimuli with the behavior of conspecifics either buffering or enhancing the response (i.e. social buffering vs. social contagion). KEY MESSAGES: Cognitive appraisal of stressors occurs in fish, implying that the stress response is modulated by a subjective and perceptual experience of the stressor. Moreover, inter-individual consistent cognitive biases in the appraisal of stressors is also present in fish making some individuals more susceptible to stress-related diseases. Therefore, psychological stress has a health toll in fish and psychologically stressed fish can potentially have ulcers.

2.
Neurosci Biobehav Rev ; 163: 105780, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38955311

ABSTRACT

In this review, we consider the definitions and experimental approaches to emotional contagion and prosocial behaviour in mammals and explore their evolutionary conceptualisation for studying their occurrence in the evolutionarily divergent vertebrate group of ray-finned fish. We present evidence for a diverse set of fish phenotypes that meet definitional criteria for prosocial behaviour and emotional contagion and discuss conserved mechanisms that may account for some preserved social capacities in fish. Finally, we provide some considerations on how to address the question of interdependency between emotional contagion and prosocial response, highlighting the importance of recognition processes, decision-making systems, and ecological context for providing evolutionary explanations.


Subject(s)
Behavior, Animal , Biological Evolution , Emotions , Fishes , Social Behavior , Animals , Fishes/physiology , Emotions/physiology , Behavior, Animal/physiology , Humans
3.
Rev. esp. patol ; 57(2): 141-145, Abr-Jun, 2024. ilus
Article in English | IBECS | ID: ibc-232421

ABSTRACT

Extraskeletal myxoid chondrosarcoma is a rare soft tissue tumour with a high local and distant metastasis rate and limited response to chemotherapy. Meckel's diverticulum is the most frequent congenital anomaly, and it is associated with a considerable risk of malignant transformation. In this case report, we describe a 50-year-old female patient with a history of extraskeletal myxoid chondrosarcoma of the lower limb and metastasis to the forearm who went to the emergency department with abdominal pain. The investigations revealed a caecal volvulus. A lesion in the middle third of the ileum was incidentally discovered and removed during surgery. Pathology examination revealed a Meckel's diverticulum adenocarcinoma, with metastasis of extraskeletal myxoid chondrosarcoma. Resection was complete; however, the patient had diffuse metastatic pulmonary disease and died eight months later due to disease progression. This mechanism of tumour-to-tumour metastasis is described in other locations, but, regarding the Meckel's diverticulum, this is a unique situation, previously unreported in the literature. (AU)


El condrosarcoma mixoide extraesquelético es un tumor de tejidos blandos poco frecuente, con una elevada tasa de recurrencia y metástasis a distancia y una respuesta limitada a la quimioterapia. El divertículo de Meckel es la anomalía congénita más frecuente y se asocia a un riesgo considerable de transformación maligna. En este caso clínico describimos a una paciente de 50 años con antecedentes de condrosarcoma mixoide extraesquelético de miembro inferior y metástasis en el antebrazo que acudió al servicio de urgencias por dolor abdominal. La exploración reveló un vólvulo cecal. Se descubrió incidentalmente una lesión en el tercio medio del íleon, que se extirpó durante la intervención quirúrgica. El examen patológico reveló un adenocarcinoma de divertículo de Meckel, afectado por metástasis de condrosarcoma mixoide extraesquelético. La resección fue completa; sin embargo, la paciente presentaba enfermedad pulmonar metastásica difusa y falleció ocho meses después debido a la progresión de la enfermedad. Este mecanismo de metástasis entre tumores está descrito en otras localizaciones, pero en lo que respecta al divertículo de Meckel, se trata de una situación única en la literatura. (AU)


Subject(s)
Humans , Female , Adult , Sarcoma , Meckel Diverticulum , Colonic Neoplasms , Neoplasm Metastasis , Chondrosarcoma
5.
Article in English | MEDLINE | ID: mdl-38733327

ABSTRACT

This study aimed to evaluate heavy metals concentrations in soils and vegetables (cabbage, lettuce, and cassava) cultivated at Matola and Beluluane Industrial Parks, and to assess health risks linked to their consumption through estimated daily intake, hazard index (HI), and incremental lifetime cancer risk. Concentrations of Al, As, Co, Cd, Cr, Ni, Pb, and Zn were determined in the two sites. Soil concentrations of As at Beluluane site and As, Cd, and Cr at Matola site exceeded reference limits of the Food and Agriculture Organization/World Health Organization, showing heavy metal contamination. At Beluluane site, all studied vegetables presented As and Pb levels higher than reference limits, Cd concentrations were higher than the reference limit in cabbage, lettuce, and cassava leaves. At Matola site crops concentrations of As, Cd, Cr, and Pb exceeded the reference limits. Zinc exceeded the reference limit in all crops except in cabbage. HIs for vegetables from Beluluane exceeded 1.0 in cabbage (2.66), lettuce (2.27), and cassava leaves (2.37). Likewise, at Matola, HIs exceeded 1.0 in lettuce (1.67), cassava leaves (1.65), and root tubers (13). We found that vegetables cultivated in industrial parks present high carcinogenic risk due to heavy metal contamination, rendering them unsuitable for human consumption.


Subject(s)
Food Contamination , Metals, Heavy , Soil Pollutants , Metals, Heavy/analysis , Humans , Soil Pollutants/analysis , Risk Assessment , Mozambique , Food Contamination/analysis , Vegetables/chemistry , Crops, Agricultural/chemistry , Environmental Monitoring
6.
Rev Esp Patol ; 57(2): 141-145, 2024.
Article in English | MEDLINE | ID: mdl-38599736

ABSTRACT

Extraskeletal myxoid chondrosarcoma is a rare soft tissue tumour with a high local and distant metastasis rate and limited response to chemotherapy. Meckel's diverticulum is the most frequent congenital anomaly, and it is associated with a considerable risk of malignant transformation. In this case report, we describe a 50-year-old female patient with a history of extraskeletal myxoid chondrosarcoma of the lower limb and metastasis to the forearm who went to the emergency department with abdominal pain. The investigations revealed a caecal volvulus. A lesion in the middle third of the ileum was incidentally discovered and removed during surgery. Pathology examination revealed a Meckel's diverticulum adenocarcinoma, with metastasis of extraskeletal myxoid chondrosarcoma. Resection was complete; however, the patient had diffuse metastatic pulmonary disease and died eight months later due to disease progression. This mechanism of tumour-to-tumour metastasis is described in other locations, but, regarding the Meckel's diverticulum, this is a unique situation, previously unreported in the literature.


Subject(s)
Adenocarcinoma , Chondrosarcoma , Meckel Diverticulum , Neoplasms, Connective and Soft Tissue , Female , Humans , Middle Aged , Meckel Diverticulum/complications , Meckel Diverticulum/diagnosis , Meckel Diverticulum/surgery , Ileum/pathology , Adenocarcinoma/pathology , Disease Progression , Chondrosarcoma/complications
7.
Life (Basel) ; 14(4)2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38672776

ABSTRACT

Propolis, a bee product, is known for its variability of chemical and bioactive profiles. However, Portuguese propolis from Gerês, normally obtained by mixing propolis from three places-Bugalho, Felgueiras and Toutelo-has shown similar chemical and biological profiles over the years. Recently, a new propolis place-Roca-was added to the apiary to replace Bugalho, lost to the 2017 wildfires, hence questioning the previously claimed constancy of Gerês propolis. To unravel to what extent the beehive relocation affected this constancy, we studied different Gerês propolis samples collected in three consecutive years (2017-2019) composed of different combinations of source places. Two honey samples, collected before (2017) and after (2018) the occurrence of the wildfire, were also investigated. Total phenolics, flavonoids and ortho-diphenols contents were determined and the antioxidant and antimicrobial activities were evaluated, using the DPPH assay and the agar dilution method, respectively. Although both antimicrobial and antioxidant activities were generally in the ranges usually obtained from Gerês propolis, some variations were detected for the samples, with different compositions when compared to previous years. This work reinforces the importance of the consistency of a combination of several factors for the protection and preservation of the flora near the hives, providing bee products with more constant chemical and biological profiles over the years.

8.
Microorganisms ; 12(3)2024 Feb 23.
Article in English | MEDLINE | ID: mdl-38543501

ABSTRACT

Addressing pressing health concerns, modern medical research seeks to identify new antimicrobials to combat drug resistance, novel molecules for cancer treatment, and antioxidants for inflammation-related diseases. Pisolithus (Basidiomycota) is a ubiquitous and widely distributed fungal genus in forest ecosystems, known for establishing ectomycorrhizal associations with a range of host plants, enhancing their growth, and conferring protection against biotic and abiotic stresses. Beyond ecological applications, Pisolithus yields bioactive compounds with medicinal potential. This comprehensive review explores the transversal biological activity of Pisolithus fungi, aiming to provide a thorough overview of their antimicrobial, anticancer, and antioxidant potential. The focus is on elucidating bioactive compounds within Pisolithus to trigger further research for innovative applications. Compounds from Pisolithus displayed antimicrobial activity against a broad spectrum of microorganisms, including antibiotic-resistant bacteria. The efficacy of Pisolithus-derived compounds matched established medications, emphasizing their therapeutic potential. In anticancer research, the triterpene pisosterol stood out with documented cytotoxicity against various cancer cell lines, showcasing promise for novel anticancer therapies. Pisolithus was also recognized as a potential source of antioxidants, with basidiocarps exhibiting high antioxidant activity. In vivo validation and comprehensive studies on a broader range of compounds, together with mechanistic insights into the mode of action of Pisolithus-derived compounds, are compelling areas for future research.

9.
GE Port J Gastroenterol ; 31(1): 54-59, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38476302

ABSTRACT

Introduction: Embryonal sarcoma of the liver (ESL) is a rare neoplasm of the liver occurring mainly in paediatric ages. Making the correct diagnosis can be challenging as the laboratory and radiological findings that are often nonspecific, and the tumour immunophenotype is poorly defined and even somewhat variable. Case Presentation: A large epigastric mass was detected in a computerized tomography scan of a 43-year-old woman presenting with abdominal pain and bloating. The mass was biopsied and submitted to histopathological study. Microscopically the tumour had sarcomatoid features and showed multinucleated cells with periodic acid-Schiff (PAS)-positive globules. Immunostaining revealed positivity for vimentin, CD10, glypican-3, and α1-antitrypsin and negativity for keratins, muscle, adipocytic, and melanocytic differentiation markers. The patient was then submitted to a left hepatectomy with similar histological findings. Discussion: ESL in adults is a rarity and its diagnosis requires the exclusion of other entities. While some microscopic features are very common, they remain nonspecific. The main feature is the presence of multinucleated cells with PAS-positive hyaline globules. While ancillary testing is key, the immunophenotype also lacks specificity and ESL may have variable staining for glypican-3 and epithelial or muscle differentiation markers. Although it has been described for more than 3 decades, the prognosis and optimal treatment are still not well defined, but surgery has yielded favourable results.


Introdução: O sarcoma embrionario do figado (SEF) e uma neoplasia rara do figado que ocorre principalmente em idades pediatricas. Fazer o diagnostico correto pode ser um desafio, uma vez que os achados laboratoriais e radiologicos sao muitas vezes inespecificos e o imunofenotipo desta entidade e mal definido e algo variavel. Apresentação do caso: Foi detetada em tomografia computorizada (CT) abdominal uma massa epigastrica volu-mosa numa mulher de 43 anos apresentando dor abdominal e distensao abdominal. A massa foi biopsada e submetida a estudo histopatologico. Microscopicamente, o tumor tinha caracteristicas sarcomatoides e apresentava celulas multinucleadas com globulos hialinos com positividade para acido periodico Schiff (APS). O estudo imunohistoquimico revelou positividade para vimentina, CD10, glipicano-3 e α1-antitripsina e negatividade para queratinas e marcadores de diferenciacao muscular, adipocitica e melanocitica. Discussão/Conclusão: O SEF no adulto e uma raridade e o seu diagnostico requer a exclusao de outras entidades. Embora algumas caracteristicas microscopicas sejam muito comuns, estas permanecem inespecificas. A principal caracteristica e a presenca de celulas multinucleadas com globulos hialinos positivos para APS. Ainda que o estudo imunohistoquimico seja fundamental, o imunofenotipo tambem carece de especificidade e o SEF pode ter marcacao variavel para glipicano− 3 e marcadores de diferenciacao epitelial ou muscular. Apesar de ter sido descrito ha mais de tres decadas, o prognostico e o tratamento ideal ainda nao estao bem definidos, mas a cirurgia tem apresentado resultados favoraveis.

10.
Biotechnol Bioeng ; 121(5): 1554-1568, 2024 May.
Article in English | MEDLINE | ID: mdl-38343176

ABSTRACT

The combination of physical equations with deep learning is becoming a promising methodology for bioprocess digitalization. In this paper, we investigate for the first time the combination of long short-term memory (LSTM) networks with first principles equations in a hybrid workflow to describe human embryonic kidney 293 (HEK293) culture dynamics. Experimental data of 27 extracellular state variables in 20 fed-batch HEK293 cultures were collected in a parallel high throughput 250 mL cultivation system in an industrial process development setting. The adaptive moment estimation method with stochastic regularization and cross-validation were employed for deep learning. A total of 784 hybrid models with varying deep neural network architectures, depths, layers sizes and node activation functions were compared. In most scenarios, hybrid LSTM models outperformed classical hybrid Feedforward Neural Network (FFNN) models in terms of training and testing error. Hybrid LSTM models revealed to be less sensitive to data resampling than FFNN hybrid models. As disadvantages, Hybrid LSTM models are in general more complex (higher number of parameters) and have a higher computation cost than FFNN hybrid models. The hybrid model with the highest prediction accuracy consisted in a LSTM network with seven internal states connected in series with dynamic material balance equations. This hybrid model correctly predicted the dynamics of the 27 state variables (R2 = 0.93 in the test data set), including biomass, key substrates, amino acids and metabolic by-products for around 10 cultivation days.


Subject(s)
Memory, Short-Term , Neural Networks, Computer , Humans , HEK293 Cells , Kidney
11.
Pharmaceutics ; 16(2)2024 Jan 31.
Article in English | MEDLINE | ID: mdl-38399261

ABSTRACT

Reversine is a purine derivative that has been investigated with regard to its biological effects, such as its anticancer properties and, mostly, its ability to induce the dedifferentiation of adult cells, increasing their plasticity. The obtained dedifferentiated cells have a high potential for use in regenerative procedures, such as regenerative dentistry (RD). Instead of replacing the lost or damaged oral tissues with synthetic materials, RD uses stem cells combined with matrices and an appropriate microenvironment to achieve tissue regeneration. However, the currently available stem cell sources present limitations, thus restricting the potential of RD. Based on this problem, new sources of stem cells are fundamental. This work aims to characterize mouse gingival fibroblasts (GFs) after dedifferentiation with reversine. Different administration protocols were tested, and the cells obtained were evaluated regarding their cell metabolism, protein and DNA contents, cell cycle changes, morphology, cell death, genotoxicity, and acquisition of stem cell characteristics. Additionally, their teratoma potential was evaluated after in vivo transplantation. Reversine caused toxicity at higher concentrations, with decreased cell metabolic activity and protein content. The cells obtained displayed polyploidy, a cycle arrest in the G2/M phase, and showed an enlarged size. Additionally, apoptosis and genotoxicity were found at higher reversine concentrations. A subpopulation of the GFs possessed stem properties, as supported by the increased expression of CD90, CD105, and TERT, the existence of a CD106+ population, and their trilineage differentiation capacity. The dedifferentiated cells did not induce teratoma formation. The extensive characterization performed shows that significant functional, morphological, and genetic changes occur during the dedifferentiation process. The dedifferentiated cells have some stem-like characteristics, which are of interest for RD.

12.
Org Biomol Chem ; 22(11): 2252-2263, 2024 03 13.
Article in English | MEDLINE | ID: mdl-38390694

ABSTRACT

Monitoring cell viability is critical in cell biology, pathology, and drug discovery. Most cell viability assays are cell-destructive, time-consuming, expensive, and/or hazardous. Herein, we present a series of newly synthesized 2,4,5-triaminopyrimidine derivatives able to discriminate between live and dead cells. To our knowledge, these compounds are the first fluorescent nucleobase analogues (FNAs) with cell viability monitoring potential. These new fluorescent molecules are synthesized using highly efficient and cost-effective methods and feature unprecedented photophysical properties (longer absorption and emission wavelengths, environment-sensitive emission, and unprecedented brightness within FNAs). Using a live-dead Saccharomyces cerevisiae cell and theoretical assays, the fluorescent 2,4,5-triaminopyrimidine derivatives were found to specifically accumulate inside dead cells by interacting with dsDNA grooves, thus paving the way for the emergence of novel and safe fluorescent cell viability markers emitting in the blue region. As the majority of commercially available viability dyes emit in the green to red region of the visible spectrum, these novel markers might be useful to meet the needs of blue markers for co-staining combinations.


Subject(s)
Fluorescent Dyes , Microscopy , Cell Survival
13.
Molecules ; 29(2)2024 Jan 18.
Article in English | MEDLINE | ID: mdl-38257384

ABSTRACT

In recent years, nutmeg (Myristica fragans Houtt.) has attracted considerable attention in the field of phytochemistry due to its diverse array of bioactive compounds. However, the potential application of nutmeg as a biorational for crop protection has been insufficiently explored. This study investigated the constituents of a nutmeg hydroethanolic extract via gas chromatography-mass spectrometry and vibrational spectroscopy. The research explored the extract's activity against phytopathogenic fungi and oomycetes, elucidating its mechanism of action. The phytochemical profile revealed fatty acids (including tetradecanoic acid, 9-octadecenoic acid, n-hexadecanoic acid, dodecanoic acid, and octadecanoic acid), methoxyeugenol, and elemicin as the main constituents. Previously unreported phytochemicals included veratone, gelsevirine, and montanine. Significant radial growth inhibition of mycelia was observed against Botrytis cinerea, Colletotrichum acutatum, Diplodia corticola, Phytophthora cinnamomi, and especially against Fusarium culmorum. Mode of action investigation, involving Saccharomyces cerevisiae labeled positively with propidium iodide, and a mutant strain affected in ERG6, encoding sterol C-24 methyltransferase, suggested that the extract induces a necrotic type of death and targets ergosterol biosynthesis. The evidence presented underscores the potential of nutmeg as a source of new antimicrobial agents, showing particular promise against F. culmorum.


Subject(s)
Myristica , Saccharomyces cerevisiae , Crop Protection , Ergosterol , Plant Extracts
14.
Gastroenterology ; 166(5): 886-901.e7, 2024 05.
Article in English | MEDLINE | ID: mdl-38096955

ABSTRACT

BACKGROUND & AIMS: Metabolic and transcriptional programs respond to extracellular matrix-derived cues in complex environments, such as the tumor microenvironment. Here, we demonstrate how lysyl oxidase (LOX), a known factor in collagen crosslinking, contributes to the development and progression of cholangiocarcinoma (CCA). METHODS: Transcriptomes of 209 human CCA tumors, 143 surrounding tissues, and single-cell data from 30 patients were analyzed. The recombinant protein and a small molecule inhibitor of the LOX activity were used on primary patient-derived CCA cultures to establish the role of LOX in migration, proliferation, colony formation, metabolic fitness, and the LOX interactome. The oncogenic role of LOX was further investigated by RNAscope and in vivo using the AKT/NICD genetically engineered murine CCA model. RESULTS: We traced LOX expression to hepatic stellate cells and specifically hepatic stellate cell-derived inflammatory cancer-associated fibroblasts and found that cancer-associated fibroblast-driven LOX increases oxidative phosphorylation and metabolic fitness of CCA, and regulates mitochondrial function through transcription factor A, mitochondrial. Inhibiting LOX activity in vivo impedes CCA development and progression. Our work highlights that LOX alters tumor microenvironment-directed transcriptional reprogramming of CCA cells by facilitating the expression of the oxidative phosphorylation pathway and by increasing stemness and mobility. CONCLUSIONS: Increased LOX is driven by stromal inflammatory cancer-associated fibroblasts and correlates with diminished survival of patients with CCA. Modulating the LOX activity can serve as a novel tumor microenvironment-directed therapeutic strategy in bile duct pathologies.


Subject(s)
Bile Duct Neoplasms , Cancer-Associated Fibroblasts , Cholangiocarcinoma , Hepatic Stellate Cells , Protein-Lysine 6-Oxidase , Tumor Microenvironment , Humans , Bile Duct Neoplasms/pathology , Bile Duct Neoplasms/metabolism , Bile Duct Neoplasms/genetics , Bile Duct Neoplasms/enzymology , Cancer-Associated Fibroblasts/metabolism , Cancer-Associated Fibroblasts/pathology , Cancer-Associated Fibroblasts/enzymology , Cell Line, Tumor , Cell Movement , Cell Proliferation , Cholangiocarcinoma/pathology , Cholangiocarcinoma/metabolism , Cholangiocarcinoma/genetics , Cholangiocarcinoma/enzymology , Gene Expression Regulation, Neoplastic , Hepatic Stellate Cells/metabolism , Hepatic Stellate Cells/pathology , Hepatic Stellate Cells/enzymology , Neoplastic Stem Cells/pathology , Neoplastic Stem Cells/metabolism , Neoplastic Stem Cells/enzymology , Oxidative Phosphorylation , Protein-Lysine 6-Oxidase/metabolism , Protein-Lysine 6-Oxidase/genetics , Signal Transduction
15.
Opt Lett ; 49(1): 53-56, 2024 Jan 01.
Article in English | MEDLINE | ID: mdl-38134150

ABSTRACT

This manuscript presents a wavelength-division multiplexing (WDM)-based photonic beamformer for an RF phased array antenna transmitter, capable of simultaneously generating multiple beams using the same optical spectrum. In the proposed architecture, for each RF beam, a WDM signal comprising the modulated RF sidebands undergoes complex-valued filtering, while another WDM signal with the same channels, but carrying only optical carriers, goes through an optical frequency-shifting stage. The proposed architecture allows the same WDM channels to be reused for multiple RF beams. The detection of the frequency-shifted optical carrier and the filtered RF sideband of each WDM channel at the photodetector produces a frequency-converted, correctly weighted signal to be fed to each antenna element. The features described herein are analytically derived, numerically simulated, and experimentally demonstrated. Results showcase two independent beams being transmitted in different directions.

17.
NPJ Breast Cancer ; 9(1): 100, 2023 Dec 15.
Article in English | MEDLINE | ID: mdl-38102162

ABSTRACT

Liver is the third most common organ for breast cancer (BC) metastasis. Two main histopathological growth patterns (HGP) exist in liver metastases (LM): desmoplastic and replacement. Although a reduced immunotherapy efficacy is reported in patients with LM, tumor-infiltrating lymphocytes (TIL) have not yet been investigated in BCLM. Here, we evaluate the distribution of the HGP and TIL in BCLM, and their association with clinicopathological variables and survival. We collect samples from surgically resected BCLM (n = 133 patients, 568 H&E sections) and post-mortem derived BCLM (n = 23 patients, 97 H&E sections). HGP is assessed as the proportion of tumor liver interface and categorized as pure-replacement ('pure r-HGP') or any-desmoplastic ('any d-HGP'). We score the TIL according to LM-specific guidelines. Associations with progression-free (PFS) and overall survival (OS) are assessed using Cox regressions. We observe a higher prevalence of 'any d-HGP' (56%) in the surgical samples and a higher prevalence of 'pure r-HGP' (83%) in the post-mortem samples. In the surgical cohort, no evidence of the association between HGP and clinicopathological characteristics is observed except with the laterality of the primary tumor (p value = 0.049) and the systemic preoperative treatment before liver surgery (p value = .039). TIL is less prevalent in 'pure r-HGP' as compared to 'any d-HGP' (p value = 0.001). 'Pure r-HGP' predicts worse PFS (HR: 2.65; CI: (1.45-4.82); p value = 0.001) and OS (HR: 3.10; CI: (1.29-7.46); p value = 0.011) in the multivariable analyses. To conclude, we demonstrate that BCLM with a 'pure r-HGP' is associated with less TIL and with the worse outcome when compared with BCLM with 'any d-HGP'. These findings suggest that HGP could be considered to refine treatment approaches.

18.
Explor Target Antitumor Ther ; 4(4): 583-599, 2023.
Article in English | MEDLINE | ID: mdl-37720343

ABSTRACT

Targeting the B-cell lymphoma 2 (Bcl-2) family proteins has been the backbone for hematological malignancies with overall survival improvements. The Bcl-2 family is a major player in apoptosis regulation and, has captured the researcher's interest in the treatment of solid tumors. Sarcomas are a heterogeneous group of diseases, comprising several entities, with high morbidity and mortality and with few specific therapies available. The treatment for sarcomas is based on platinum regimens, with variable results and poor outcomes, especially in advanced lesions. The high number of different sarcoma entities makes treatment standardization as well as the performance of clinical trials difficult. The use of Bcl-2 family members modifiers has revealed promising results in in vitro and in vivo models and may be a valid option, especially when used in combination with chemotherapy. In this article, a revision of these results and possibilities for the use of Bcl-2 family members inhibitors in sarcomas was performed.

19.
Enzyme Microb Technol ; 171: 110322, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37722241

ABSTRACT

Phenazines, including pyocyanin (PYO) and 1-hydroxyphenazine (1-HP) are extracellular secondary metabolites and multifunctional pigments of Pseudomonas aeruginosa responsible for its blue-green color. These versatile molecules are electrochemically active, involved in significant biological activities giving fitness to the host, but also recognized as antimicrobial and anticancer agents. Their wider application is still limited partly due to the cost of carbon substrate for production, which can be solved by the utilization of carbon from food waste within the biorefinery concept. In this study, a variety of food waste streams (banana peel, potato peel, potato washing, stale bread, yoghurt, processed meat, boiled eggs and mixed canteen waste) was used as sole nutrient source in submerged cultures of P. aeruginosa BK25H. Stale bread was identified as the most suitable substrate to support phenazine biopigments production and bacterial growth. This was further increased in 5-liter fermenter when on average 5.2 mg L-1 of PYO and 4.4 mg L-1 of 1-HP were purified after 24 h batch cultivations from the fermentation medium consisting of homogenized stale bread in tap water. Purified biopigments showed moderate antimicrobial activity, and showed different toxicity profiles, with PYO not being toxic against Caenorhabditis elegans, a free-living soil nematode up to 300 µg mL-1 and 1-HP showing lethal effects at 75 µg mL-1. Therefore, stale bread waste stream with minimal pretreatment should be considered as suitable biorefinery feedstock, as it can support the production of valuable biopigments such as phenazines.

20.
Environ Sci Pollut Res Int ; 30(48): 105675-105684, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37715912

ABSTRACT

With the growing interest to exploit mineral resources in the deep-sea, there is the need to establish guidelines and frameworks to support hazard and risk assessment schemes. The present study used a subtidal species of filter-feeding bivalve, the clam Spisula solida, as a proxy to better understand the impacts of sediment plumes in marine organisms under hyperbaric conditions. Four concentrations of suspended sediments (0 g/L, 1 g/L, 2 g/L, and 4 g/L) were used in a mixture with different grain sizes at 4 Bar for 96 h. Functional (filtration rate-FR) and biochemical endpoints (catalase-CAT, glutathione s-transferase-GST, and lipid peroxidation-LPO) were analyzed in the gonads, digestive gland, and gills of S. solida after a 96-h exposure at 4 Bar (the natural limit of the species vertical distribution). The FR showed a decreasing trend with the increasing sediment concentrations (significant effects at 2 and 4 g/L). Additionally, significant changes were observed for some of the tested oxidative stress biomarkers, which were concentration and tissue-dependent, i.e., CAT activity was significantly elevated in gills (1 g/L treatment), and GST was decreased in digestive gland (1 g/L treatment). Overall, the results show that suspended sediments, at 2 and 4 g/L, have negative functional impacts in the bivalve S. solida providing additional insights to improve hazard assessment of deep-sea mining. These findings represent a step forward to ensure the mitigation of the potential negative effects of deep-sea resource exploitation.


Subject(s)
Bivalvia , Spisula , Water Pollutants, Chemical , Animals , Spisula/metabolism , Catalase/metabolism , Oxidative Stress , Digestion , Lipid Peroxidation , Gills/metabolism , Water Pollutants, Chemical/chemistry , Biomarkers/metabolism , Glutathione Transferase/metabolism
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