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1.
Int J Surg ; 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38608195

RESUMO

INTRODUCTION: Involvement of the inferior vena cava (IVC) and hepatic veins (HV) has been considered a relative contraindication to hepatic resection for primary and metastatic liver tumors. However, patients affected by tumors extending to the IVC have limited therapeutic options and suffer worsening of quality of life due to IVC compression. METHODS: Cases of primary and metastatic liver tumors with vena cava infiltration from 10 international centers were collected (7 European, 1 US, 2 Brazilian, 1 Indian) were collected. Inclusion criteria for the study were major liver resection with concomitant vena cava replacement. Clinical data and short-term outcomes were analyzed. RESULTS: 36 cases were finally included in the study. Median tumor max size was 98 mm (range: 25-250). A biliary reconstruction was necessary in 28% of cases, while a vascular reconstruction other than vena cava in 34% of cases. Median operative time was 462 min (range: 230-750), with 750 median ml of estimated blood loss and a median of one pRBC transfused intraoperatively (range: 0-27). Median ICU stay was 4 days (range: 1-30) with overall in-hospital stay of 15 days (range: 3-46), post-operative CCI score of 20.9 (range: 0-100), 12% incidence of PHLF grade B-C. Five patients died in a 90-days interval from surgery, 1 due to heart failure, 1 due to septic shock and 3 due to multiorgan failure. With a median follow-up of 17 months (interquartile range: 11-37), the estimated five-years overall survival was 48% (95% CI: 27%-66%), and five-year cumulative incidence of tumor recurrence was 55% (95% CI: 33%-73%). CONCLUSIONS: Major liver resections with vena cava replacement can be performed with satisfactory results in expert HPB centers. This surgical strategy represents a feasible alternative for otherwise unresectable lesions and is associated with favorable prognosis compared to non-operative management, especially in patients affected by intrahepatic cholangiocarcinoma.

2.
Biology (Basel) ; 13(3)2024 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-38534433

RESUMO

The consumption of non-sugar sweeteners (NSS) has increased during pregnancy. The European Food Safety Agency suggested that steviol glycosides, such as Rebaudioside A (RebA), the major sweetener component of stevia, are safe for humans up to a dose of 4 mg/kg body weight/day. However, the World Health Organization recommended in 2023 the restraint of using NSS, including stevia, at any life stage, highlighting the need to study NSS safety in early periods of development. We aimed to study the mitochondrial and cardiometabolic effects of long-term RebA consumption during the reproductive stage of the life cycle. Female rats were exposed to RebA (4 mg steviol equivalents/kg body weight/day) in the drinking water from 4 weeks before mating until weaning. Morphometry, food and water consumption, glucose and lipid homeostasis, heart structure, function, and mitochondrial function were assessed. RebA showed an atrophic effect in the heart, decreasing cardiomyocyte cross-sectional area and myocardial fibrosis without repercussions on cardiac function. Mitochondrial and myofilamentary functions were not altered. Glucose tolerance and insulin sensitivity were not affected, but fasting glycemia and total plasma cholesterol decreased. This work suggests that this RebA dose is safe for female consumption during the reproductive stage, from a cardiometabolic perspective. However, studies on the effects of RebA exposure on the offspring are mandatory.

3.
J Hazard Mater ; 469: 133863, 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38430591

RESUMO

This article provides a comprehensive study of ecosystem rehabilitation methods widely used in the 21st century, focusing on Europe. The review covers the evolution and trends in scientific article publication, identification of European countries demonstrating high publication outputs, collaboration patterns, leading journals, and thematic areas. Additionally, it examines primary stressors in European aquatic ecosystems, and different methods and treatments commonly employed for remediation purposes. The analysis of selected articles revealed a significant increase in studies over time, driven by public awareness and financial incentives from national, European and global organizations. Italy, Portugal and Spain were the leading countries in degraded ecosystem rehabilitation studies, mainly focusing on remediating contaminated areas where metals were identified as the primary stressor (chemical pollution). Chemical remediation method emerged as the most used, closely followed by biological remediation method, which have gained prominence in recent years due to their ecological, economic, and social combined benefits. Furthermore, recent studies demonstrate a growing trend towards the combined use of more than one treatment/method to rehabilitate ecosystems, particularly with biological treatments. This combined approach has the potential for synergistic effects in achieving more effective rehabilitation and their sustainability in the long term, thus, a focus for future research.


Assuntos
Ecossistema , Recuperação e Remediação Ambiental , Poluição Ambiental , Europa (Continente) , Espanha , Itália
4.
Adv Mater ; : e2402014, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38551106

RESUMO

Direct Laser Writing (DLW) has been increasingly selected as a microfabrication route for efficient, cost-effective, high-resolution material synthesis and conversion. Concurrently, lasers participate in the patterning and assembly of functional geometries in several fields of application, of which electronics stand out. In this review, recent advances and strategies based on DLW for electronics microfabrication are surveyed and outlined, based on laser material growth strategies. First, the main DLW parameters influencing material synthesis and transformation mechanisms are summarized, aimed at selective, tailored writing of conductive and semiconducting materials. Additive and transformative DLW processing mechanisms are discussed, to open space to explore several categories of materials directly synthesized or transformed for electronics microfabrication. These include metallic conductors, metal oxides, transition metal chalcogenides and carbides, laser-induced graphene, and their mixtures. By accessing a wide range of material types, DLW-based electronic applications are explored, including processing components, energy harvesting and storage, sensing, and bioelectronics. The expanded capability of lasers to participate in multiple fabrication steps at different implementation levels, from material engineering to device processing, indicates their future applicability to next-generation electronics, where more accessible, green microfabrication approaches integrate lasers as comprehensive tools.

5.
Curr Oncol ; 31(2): 1113-1128, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38392077

RESUMO

The reference to vitiligo-like lesions (VLLs) induced by immune checkpoint inhibitors (ICIs) as a valuable predictive marker of treatment success of immunotherapy with ICIs in melanoma has been mentioned in the literature. Its role in non-small cell lung cancer (NSCLC)-treated patients remains a poorly recognized phenomenon with uncertain significance regarding its predictive value. A retrospective, observational, single-center report was performed, with descriptive analysis of clinicopathological and treatment characteristics of patients with stage IV NSCLC who developed ICI-induced VLL between January 2018 and December 2022, contextualized in a comprehensive review of the literature and reported cases regarding this phenomenon. During the first 5 years' experience of ICI use in stage IV NSCLC treatment, three cases of ICI-induced VLLs were diagnosed. In line with the previous reports, two of the three presented cases exhibited treatment response and favorable prognosis. The recognition and understanding of the pathophysiological processes underlying ICI-induced VLLs may represent a promising opportunity to identify a predictive marker of tumor response to ICIs, with impact in treatment selection and patient management. It also may contribute to the recognition of new patterns of molecular expression that could lead to improvements in therapeutic development.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Vitiligo , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Imunoterapia/efeitos adversos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Estudos Retrospectivos , Vitiligo/etiologia
6.
Am J Physiol Heart Circ Physiol ; 326(5): H1193-H1203, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38334973

RESUMO

Pressure overload-induced hypertrophy compromises cardiac stretch-induced compliance (SIC) after acute volume overload (AVO). We hypothesized that SIC could be enhanced by physiological hypertrophy induced by pregnancy's chronic volume overload. This study evaluated SIC-cardiac adaptation in pregnant women with or without cardiovascular risk (CVR) factors. Thirty-seven women (1st trimester, 1stT) and a separate group of 31 (3rd trimester, 3rdT) women [healthy or with CVR factors (obesity and/or hypertension and/or with gestational diabetes)] underwent echocardiography determination of left ventricular end-diastolic volume (LVEDV) and E/e' before (T0), immediately after (T1), and 15 min after (T2; SIC) AVO induced by passive leg elevation. Blood samples for NT-proBNP quantification were collected before and after the AVO. Acute leg elevation significantly increased inferior vena cava diameter and stroke volume from T0 to T1 in both 1stT and 3rdT, confirming AVO. LVEDV and E/e' also increased immediately after AVO (T1) in both 1stT and 3rdT. SIC adaptation (T2, 15 min after AVO) significantly decreased E/e' in both trimesters, with additional expansion of LVEDV only in the 1stT. NT-pro-BNP increased slightly after AVO but only in the 1stT. CVR factors, but not parity or age, significantly impacted SIC cardiac adaptation. A distinct functional response to SIC was observed between 1stT and 3rdT, which was influenced by CVR factors. The LV of 3rdT pregnant women was hypertrophied, showing a structural limitation to dilate with AVO, whereas the lower LV filling pressure values suggest increased diastolic compliance.NEW & NOTEWORTHY The sudden increase of volume overload triggers an acute myocardial stretch characterized by an immediate rise in contractility by the Frank-Starling mechanism, followed by a progressive increase known as the slow force response. The present study is the first to characterize echocardiographically the stretch-induced compliance (SIC) mechanism in the context of physiological hypertrophy induced by pregnancy. A distinct functional adaptation to SIC was observed between first and third trimesters, which was influenced by cardiovascular risk factors.


Assuntos
Adaptação Fisiológica , Fatores de Risco de Doenças Cardíacas , Humanos , Feminino , Gravidez , Adulto , Função Ventricular Esquerda , Cardiomegalia/fisiopatologia , Cardiomegalia/diagnóstico por imagem , Cardiomegalia/etiologia , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Complicações Cardiovasculares na Gravidez/fisiopatologia , Complicações Cardiovasculares na Gravidez/diagnóstico por imagem , Complicações Cardiovasculares na Gravidez/sangue , Volume Sistólico , Terceiro Trimestre da Gravidez , Diabetes Gestacional/fisiopatologia , Complacência (Medida de Distensibilidade) , Primeiro Trimestre da Gravidez , Obesidade/fisiopatologia , Obesidade/complicações , Fatores de Risco
7.
Cureus ; 16(1): e52176, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38344619

RESUMO

Background This study aimed to assess functional and anatomical outcomes after one month of treatment with a single intravitreal injection (IVI) of brolucizumab in patients with diabetic macular edema (DME). Methodology A retrospective study was conducted on eyes with DME who received a single IVI of brolucizumab. The study was designed to assess visual function and optical coherence tomography (OCT) biomarkers at baseline and one month following a single brolucizumab IVI. A sub-analysis was conducted between the following two groups: group 1 - treatment with brolucizumab due to burden, needle phobia, or non-compliance (responders to standard anti-vascular endothelial growth factor (VEGF) or naïve); and group 2 - non-responsive to previous therapies (standard anti-VEGF ± corticosteroids). The main outcome measures included best-corrected visual acuity (BCVA; Early Treatment of Diabetic Retinopathy Study (ETDRS) letters), central foveal thickness, and OCT biomarkers such as the presence of subretinal fluid, the number of hyperreflective dots, the disorganization of retinal inner layers, the disruption of outer plexiform layer, external limiting membrane and ellipsoid zone, the presence of cysts in the nuclear layers (outer (ONL) and inner (INL)), and the number of cysts in ONL versus those in the INL. Safety outcomes were assessed. Results A total of 59 eyes from 42 patients were included, of which 47 eyes were in group 1 and 12 eyes were in group 2. At one month, patients had an improvement of two ETDRS letters on BCVA (p = 0.020), lower central foveal thickness (p < 0.001), fewer hyperreflective dots (p = 0.016), less outer plexiform layer disruption (p = 0.004), less inner and outer nuclear layer cysts (p < 0.001 and p = 0.001, respectively) and better relationship between ONL and INL cysts (p = 0.022). Results were significant in the subgroup of patients with previous responsive DME. No adverse events were reported. Conclusions This study demonstrates the effectiveness and safety after one injection of brolucizumab 6 mg in the management of DME, especially in previously responsive DME patients.

8.
Clin Transl Oncol ; 2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38332225

RESUMO

Urothelial carcinoma is a significant global health concern that accounts for a substantial part of cancer diagnoses and deaths worldwide. The tumor microenvironment is a complex ecosystem composed of stromal cells, soluble factors, and altered extracellular matrix, that mutually interact in a highly immunomodulated environment, with a prominent role in tumor development, progression, and treatment resistance. This article reviews the current state of knowledge of the different cell populations that compose the tumor microenvironment of urothelial carcinoma, its main functions, and distinct interactions with other cellular and non-cellular components, molecular alterations and aberrant signaling pathways already identified. It also focuses on the clinical implications of these findings, and its potential to translate into improved quality of life and overall survival. Determining new targets or defining prognostic signatures for urothelial carcinoma is an ongoing challenge that could be accelerated through a deeper understanding of the tumor microenvironment.

9.
Am J Primatol ; 86(5): e23603, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38293796

RESUMO

Identifying novel medicinal resources in chimpanzee diets has historically presented challenges, requiring extensive behavioral data collection and health monitoring, accompanied by expensive pharmacological analyses. When putative therapeutic self-medicative behaviors are observed, these events are often considered isolated occurrences, with little attention paid to other resources ingested in combination. For chimpanzees, medicinal resource combinations could play an important role in maintaining well-being by tackling different symptoms of an illness, chemically strengthening efficacy of a treatment, or providing prophylactic compounds that prevent future ailments. We call this concept the self-medicative resource combination hypothesis. However, a dearth of methodological approaches for holistically investigating primate feeding ecology has limited our ability to identify nonrandom resource combinations and explore potential synergistic relationships between medicinal resource candidates. Here we present two analytical tools that test such a hypothesis and demonstrate these approaches on feeding data from the Sonso chimpanzee community in Budongo Forest, Uganda. Using 4 months of data, we establish that both collocation and APRIORI analyses are effective exploratory tools for identifying binary combinations, and that APRIORI is effective for multi-item rule associations. We then compare outputs from both methods, finding up to 60% agreement, and propose APRIORI as more effective for studies requiring control over confidence intervals and those investigating nonrandom associations between more than two resources. These analytical tools, which can be extrapolated across the animal kingdom, can provide a cost-effective and efficient method for targeting resources for further pharmacological investigation, potentially aiding in the discovery of novel medicines.


Assuntos
Dieta , Pan troglodytes , Animais , Dieta/veterinária , Alimentos , Ecologia , Florestas , Uganda
10.
Eur J Pharmacol ; 966: 176336, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38272343

RESUMO

Heart failure with preserved ejection fraction (HFpEF) is a syndrome characterized by impaired cardiovascular reserve in which therapeutic options are scarce. Our aim was to evaluate the inodilator levosimendan in the ZSF1 obese rat model of HFpEF. Twenty-week-old male Wistar-Kyoto (WKY), ZSF1 lean (ZSF1 Ln) and ZSF1 obese rats chronically treated for 6-weeks with either levosimendan (1 mg/kg/day, ZSF1 Ob + Levo) or vehicle (ZSF1 Ob + Veh) underwent peak-effort testing, pressure-volume (PV) haemodynamic evaluation and echocardiography (n = 7 each). Samples were collected for histology and western blotting. In obese rats, skinned and intact left ventricular (LV) cardiomyocytes underwent in vitro functional evaluation. Seven additional ZSF1 obese rats underwent PV evaluation to assess acute levosimendan effects (10 µg/kg + 0.1 µg/kg/min). ZSF1 Ob + Veh presented all hallmarks of HFpEF, namely effort intolerance, elevated end-diastolic pressures and reduced diastolic compliance as well as increased LV mass and left atrial area, cardiomyocyte hypertrophy and increased interstitial fibrosis. Levosimendan decreased systemic arterial pressures, raised cardiac index, and enhanced LV relaxation and diastolic compliance in both acute and chronic experiments. ZSF1 Ob + Levo showed pronounced attenuation of hypertrophy and interstitial fibrosis alongside increased effort tolerance (endured workload raised 38 %) and maximum O2 consumption. Skinned cardiomyocytes from ZSF 1 Ob + Levo showed a downward shift in sarcomere length-passive tension relationship and intact cardiomyocytes showed decreased diastolic Ca2+ levels and enhanced Ca2+ sensitivity. On molecular grounds, levosimendan enhanced phosphorylation of phospholamban and mammalian target of rapamycin. The observed effects encourage future clinical trials with levosimendan in a broad population of HFpEF patients.


Assuntos
Insuficiência Cardíaca , Humanos , Ratos , Masculino , Animais , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/tratamento farmacológico , Volume Sistólico , Simendana/farmacologia , Ratos Endogâmicos WKY , Obesidade/complicações , Obesidade/tratamento farmacológico , Fibrose , Hipertrofia , Mamíferos
11.
Nat Chem Biol ; 2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38172604

RESUMO

Translation termination is an essential cellular process, which is also of therapeutic interest for diseases that manifest from premature stop codons. In eukaryotes, translation termination requires eRF1, which recognizes stop codons, catalyzes the release of nascent proteins from ribosomes and facilitates ribosome recycling. The small molecule SRI-41315 triggers eRF1 degradation and enhances translational readthrough of premature stop codons. However, the mechanism of action of SRI-41315 on eRF1 and translation is not known. Here we report cryo-EM structures showing that SRI-41315 acts as a metal-dependent molecular glue between the N domain of eRF1 responsible for stop codon recognition and the ribosomal subunit interface near the decoding center. Retention of eRF1 on ribosomes by SRI-41315 leads to ribosome collisions, eRF1 ubiquitylation and a higher frequency of translation termination at near-cognate stop codons. Our findings reveal a new mechanism of release factor inhibition and additional implications for pharmacologically targeting eRF1.

12.
Int J Pharm ; 650: 123659, 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38042383

RESUMO

Among the unique characteristics associated to gold nanoparticles (AuNPs) in biomedicine, their ability to convert light energy into heat opens ventures for improved cancer therapeutic options, such as photothermal therapy (PTT). PTT relies on the local hyperthermia of tumor cells upon irradiation with light beams, and the association of AuNPs with radiation within the near infrared (NIR) range constitutes an advantageous strategy to potentially improve PTT efficacy. Herein, it was explored the effect of the gold salt on the AuNPs' physicochemical and optical properties. Mostly spherical-like negatively charged AuNPs with variable sizes and absorbance spectra were obtained. In addition, photothermal features were assessed using in vitro phantom models. The best formulation showed the ability to increase their temperature in aqueous solution up to 19 °C when irradiated with a NIR laser for 20 min. Moreover, scanning transmission electron microscopy confirmed the rearrangement of the gold atoms in a face-centered cubic structure, which further allowed to calculate the photothermal conversion efficiency upon combination of theoretical and experimental data. AuNPs also showed local retention after being locally administered in in vivo models. These last results obtained by computerized tomography allow to consider these AuNPs as promising elements for a PTT system. Moreover, AuNPs showed high potential for PTT by resulting in in vitro cancer cells' viability reductions superior to 70 % once combine with 5 min of NIR irradiation.


Assuntos
Ouro , Nanopartículas Metálicas , Ouro/química , Fototerapia , Terapia Fototérmica , Nanopartículas Metálicas/química , Linhagem Celular Tumoral
13.
Eur J Ophthalmol ; 34(1): 233-244, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37475207

RESUMO

INTRODUCTION: A detailed understanding of the anatomical and structural changes occurring in the retina following intravitreal fluocinolone acetonide implantation may help improve the management and prognosis of persistent or recurrent diabetic macular edema (DME). METHODS: Overall, 45 eyes (from 35 patients) with refractory center-involved DME received an intravitreal fluocinolone acetonide implant. They were monitored at baseline and at 6, 12, 24, and 36 months for best-corrected visual acuity (BCVA), central foveal thickness (CFT), and the seven retinal parameters used in the classification of diabetic maculopathy recently developed at the European School for Advanced Studies in Ophthalmology (ESASO). RESULTS: Within 6 months of implantation, significant improvements were evident in BCVA, CFT, maculopathy stage, and the percentage of eyes with: intraretinal cysts; CFT > 30% above the upper normal value; and disrupted or absent ellipsoid zone (EZ) and/or external limiting membrane (ELM). Significant improvements were still maintained at 36 months post-implantation. At month 36, early treatment with the implant (i.e., after < 6 previous intravitreal injections for DME) trended toward being more effective than later treatment in improving BCVA, CFT, maculopathy stage, and the percentage of eyes with CFT > 30% above the upper normal value. However, statistical significance was not achieved. CONCLUSION: In persistent or recurrent DME, fluocinolone acetonide implantation can be effective in improving maculopathy stage and reducing the percentage of eyes with: intraretinal cysts; CFT > 30% above the upper normal value; and disrupted or absent EZ and/or ELM. It can also increase BCVA and reduce CFT.


Assuntos
Cistos , Retinopatia Diabética , Edema Macular , Oftalmologia , Humanos , Fluocinolona Acetonida , Retinopatia Diabética/tratamento farmacológico , Edema Macular/diagnóstico , Edema Macular/tratamento farmacológico , Edema Macular/etiologia , Tomografia de Coerência Óptica , Retina , Injeções Intravítreas , Implantes de Medicamento/uso terapêutico , Estudos Retrospectivos
14.
Ann Surg Oncol ; 31(1): 81-89, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37718337

RESUMO

INTRODUCTION: Perihilar cholangiocarcinoma is a difficult cancer to treat with frequent vascular invasion, local recurrence, and poor survival. Due to the need for biliary anastomosis and potential vascular resection, the standard approach is an open operation. Suboptimal outcomes after laparoscopic resection had been sporadically reported by high-volume centers. In this first, Trans-Atlantic, multicenter study, we report our outcomes of robotic resection for perihilar cholangiocarcinoma. This is the largest study of its kind in the Western hemisphere. METHODS: Between 2016 and 2023, we prospectively followed patients undergoing robotic resection for perihilar cholangiocarcinoma at three, high-volume, robotic, liver-surgery centers. RESULTS: Thirty-eight patients underwent perihilar cholangiocarcinoma utilizing the robotic technique; Klatskin type-3 was the most common. The median age was 72 years, and 82% of the patients underwent preoperative biliary drainage. Median operative time was 481 minutes with a median estimated blood loss of 200 mL. The number of harvested lymph nodes was seven, and 11 (28%) patients yielded positive lymph nodes. Three patients required vascular reconstruction; 18% of patients had >1 biliary anastomosis. R0 resection margins were achieved in 82% of patients. Clavien-Dindo Grade ≥3 complications were seen in 16% of patients. The length of stay was 6 days. Five patients had an unplanned readmission within 30 days. One patient died within 30 days. With a median follow-up of 15 months, 68% of patients are alive without disease, 13% recurred, and 19% died. CONCLUSIONS: Application of the robotic platform for perihilar cholangiocarcinoma is safe and feasible with acceptable short-term clinical and oncological outcomes.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Tumor de Klatskin , Procedimentos Cirúrgicos Robóticos , Robótica , Humanos , Idoso , Tumor de Klatskin/patologia , Procedimentos Cirúrgicos Robóticos/métodos , Hepatectomia/métodos , Neoplasias dos Ductos Biliares/patologia , Colangiocarcinoma/cirurgia , Resultado do Tratamento , Estudos Retrospectivos
17.
Osteoporos Int ; 2023 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-38055051

RESUMO

PURPOSE: Osteoporosis is a metabolic bone disease characterized by decreased bone strength and mass, which predisposes patients to fractures and is associated with high morbidity and mortality. Like osteoporosis, obesity and diabetes are systemic metabolic diseases associated with modifiable risk factors and lifestyle, and their prevalence is increasing. They are related to decreased quality of life, functional loss and increased mortality, generating high costs for health systems and representing a worldwide public health problem. Growing evidence reinforces the role of bone marrow adipose tissue (BMAT) as an influential factor in the bone microenvironment and systemic metabolism. Given the impact of obesity and diabetes on metabolism and their possible effect on the bone microenvironment, changes in BMAT behavior may explain the risk of developing osteoporosis in the presence of these comorbidities. METHODS: This study reviewed the scientific literature on the behavior of BMAT in pathological metabolic conditions, such as obesity and diabetes, and its potential involvement in the pathogenesis of bone fragility. RESULTS: Published data strongly suggest a relationship between increased BMAT adiposity and the risk of bone fragility in the context of obesity and diabetes. CONCLUSION: By secreting a broad range of factors, BMAT modulates the bone microenvironment and metabolism, ultimately affecting skeletal health. A better understanding of the relationship between BMAT expansion and metabolic disturbances observed in diabetic and obese patients will help to identify regulatory pathways and new targets for the treatment of bone-related diseases, with BMAT as a potential therapeutic target.

18.
Mar Pollut Bull ; 197: 115762, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37979526

RESUMO

Seagrass meadows provide several ecological functions that improve the overall ecological health of coastal systems and therefore, it is urgent to promote the restoration of such habitats. In Ria de Aveiro, a coastal lagoon in the Atlantic Coast of Portugal, a restoration initiative was responsible for transplanting the dwarf eelgrass Zostera noltei into a highly degraded area. This eelgrass was used as a nature-based solution (NbS) to mitigate some of the impacts of historical mercury contamination. Comparisons of key-species features (density and biomass), and some community-derived indicators (total density and biomass, species richness and Shannon-Wiener index) between the transplanted seagrass patch, their bare vicinities, and their counterpart habitats on the source area, provided signs of the effectiveness of the restoration action on the benthic communities' recovery. Indicators were higher within the restored meadow, and biomass derived indicators of the restored meadow were similar to the source meadow.


Assuntos
Mercúrio , Zosteraceae , Ecossistema , Biomassa , Portugal
19.
Front Physiol ; 14: 1271698, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37849977

RESUMO

Introduction: Management of acute myocardial infarction (MI) mandates careful optimization of volemia, which can be challenging due to the inherent risk of congestion. Increased myocardial compliance in response to stretching, known as stretch-induced compliance (SIC), has been recently characterized and partly ascribed to cGMP/cGMP-dependent protein kinase (PKG)-related pathways. We hypothesized that SIC would be impaired in MI but restored by activation of PKG, thereby enabling a better response to volume loading in MI. Methods: We conducted experiments in ex vivo rabbit right ventricular papillary muscles under ischemic and non-ischemic conditions as well as pressure-volume hemodynamic evaluations in experimental in vivo MI induced by left anterior descending artery ligation in rats. Results: Acutely stretching muscles ex vivo yielded increased compliance over the next 15 min, but not under ischemic conditions. PKG agonists, but not PKC agonists, were able to partially restore SIC in ischemic muscles. A similar effect was observed with phosphodiesterase-5 inhibitor (PDE5i) sildenafil, which was amplified by joint B-type natriuretic peptide or nitric oxide donor administration. In vivo translation revealed that volume loading after MI only increased cardiac output in rats infused with PDE5i. Contrarily to vehicle, sildenafil-treated rats showed a clear increase in myocardial compliance upon volume loading. Discussion: Our results suggest that ischemia impairs the adaptive myocardial response to acute stretching and that this may be partly prevented by pharmacological manipulation of the cGMP/PKG pathway, namely, with PDE5i. Further studies are warranted to further elucidate the potential of this intervention in the clinical setting of acute myocardial ischemia.

20.
iScience ; 26(9): 107644, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37701811

RESUMO

The Miocene was a key time in the evolution of African ecosystems witnessing the origin of the African apes and the isolation of eastern coastal forests through an expanding arid corridor. Until recently, however, Miocene sites from the southeastern regions of the continent were unknown. Here, we report the first Miocene fossil teeth from the shoulders of the Urema Rift in Gorongosa National Park, Mozambique. We provide the first 1) radiometric ages of the Mazamba Formation, 2) reconstructions of paleovegetation in the region based on pedogenic carbonates and fossil wood, and 3) descriptions of fossil teeth. Gorongosa is unique in the East African Rift in combining marine invertebrates, marine vertebrates, reptiles, terrestrial mammals, and fossil woods in coastal paleoenvironments. The Gorongosa fossil sites offer the first evidence of woodlands and forests on the coastal margins of southeastern Africa during the Miocene, and an exceptional assemblage of fossils including new species.

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