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1.
Materials (Basel) ; 17(7)2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38612033

RESUMO

Polishing after the removal of brackets is the final step in orthodontic treatment. It is simple to perform, though some studies have reported that polishing causes damage to the enamel surface. An in vitro study was made of the influence of the buccal surface convexity of the tooth upon possible enamel loss when the remaining resin and adhesive are removed after bracket decementing using two different polishing modes: a tungsten carbide bur at low and high speeds. The convexity of the buccal surface was quantified in 30 incisors and 30 premolars. A stereoscopic microscope was used to obtain photographs of the profile of the crown, and Image J software was used to calculate convexity by dividing the length of a line from the cementoenamel junction to the incisal margin by another line from the mentioned junction to the maximum convexity of the buccal surface. Brackets were cemented on all the teeth and were decemented 24 h later. In both groups, the residual composite was removed with a tungsten carbide bur at a low speed in one-half of the teeth and at a high speed in the other half. The buccal surface of each tooth was then photographed again, and the convexity was calculated and compared against the baseline value. The difference between the two values were taken to represent the enamel loss. The convexity of the premolars was significantly greater than that of the incisors, but this did not result in greater enamel loss when the same polishing mode was used. However, the tungsten carbide bur at a high speed proved more aggressive, causing significantly greater enamel loss than when used at a low speed.

2.
ACS Appl Energy Mater ; 7(7): 2779-2790, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38606034

RESUMO

An increasing number of studies focus on organic flow batteries (OFBs) as possible substitutes for the vanadium flow battery (VFB), featuring anthraquinone derivatives, such as anthraquinone-2,7-disulfonic acid (2,7-AQDS). VFBs have been postulated as a promising energy storage technology. However, the fluctuating cost of vanadium minerals and risky supply chains have hampered their implementation, while OFBs could be prepared from renewable raw materials. A critical component of flow batteries is the electrode material, which can determine the power density and energy efficiency. Yet, and in contrast to VFBs, studies on electrodes tailored for OFBs are scarce. Hence, in this work, we propose the modification of commercial carbon felts with reduced graphene oxide (rGO) and poly(ethylene glycol) for the 2,7-AQDS redox couple and to preliminarily assess its effects on the efficiency of a 2,7-AQDS/ferrocyanide flow battery. Results are compared to those of a VFB to evaluate if the benefits of the modification are transferable to OFBs. The modification of carbon felts with surface oxygen groups introduced by the presence of rGO enhanced both its hydrophilicity and surface area, favoring the catalytic activity toward VFB and OFB reactions. The results are promising, given the improved behavior of the modified electrodes. Parallels are established between the electrodes of both FB technologies.

3.
Nature ; 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38649488

RESUMO

Muscle atrophy and functional decline (sarcopenia) are common manifestations of frailty and are critical contributors to morbidity and mortality in older people1. Deciphering the molecular mechanisms underlying sarcopenia has major implications for understanding human ageing2. Yet, progress has been slow, partly due to the difficulties of characterizing skeletal muscle niche heterogeneity (whereby myofibres are the most abundant) and obtaining well-characterized human samples3,4. Here we generate a single-cell/single-nucleus transcriptomic and chromatin accessibility map of human limb skeletal muscles encompassing over 387,000 cells/nuclei from individuals aged 15 to 99 years with distinct fitness and frailty levels. We describe how cell populations change during ageing, including the emergence of new populations in older people, and the cell-specific and multicellular network features (at the transcriptomic and epigenetic levels) associated with these changes. On the basis of cross-comparison with genetic data, we also identify key elements of chromatin architecture that mark susceptibility to sarcopenia. Our study provides a basis for identifying targets in the skeletal muscle that are amenable to medical, pharmacological and lifestyle interventions in late life.

4.
Sports (Basel) ; 12(3)2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38535736

RESUMO

Hamstring injuries in soccer continue to be a challenge for professionals who work with soccer players daily. Although its origin is multifactorial, the proper management of neuromuscular fatigue during the training microcycle is a very important factor to consider. There are no clear guidelines regarding the weekly distribution of certain exercises that demand the hamstrings. The main objective of this study was to describe the usual training practices of professional European soccer teams. An international observational survey design was applied to some of the strength and conditioning coaches of professional soccer teams. The survey included different neuromuscular demanding exercises for the hamstrings. For each exercise, the strength and conditioning coaches had to respond in relation to their frequency of use and timepoint depending on the day of the weekly microcycle. Although there is no strong consensus in this regard, there does seem to be a trend when applying certain exercises, especially on the days matchday-4 and matchday-3.

5.
Cancer Med ; 13(5): e6923, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38491824

RESUMO

BACKGROUND AND STUDY AIMS: Our aim was to determine the impact of the SARS-CoV-2 pandemic on the diagnosis and prognosis of colorectal cancer (CRC). PATIENTS AND METHODS: This prospective cohort study included individuals diagnosed with CRC between March 13, 2019 and June 20, 2021 across 21 Spanish hospitals. Two time periods were compared: prepandemic (from March 13, 2019 to March 13, 2020) and pandemic (from March 14, 2020 to June 20, 2021, lockdown period and 1 year after lockdown). RESULTS: We observed a 46.9% decrease in the number of CRC diagnoses (95% confidence interval (CI): 45.1%-48.7%) during the lockdown and 29.7% decrease (95% CI: 28.1%-31.4%) in the year after the lockdown. The proportion of patients diagnosed at stage I significantly decreased during the pandemic (21.7% vs. 19.0%; p = 0.025). Centers that applied universal preprocedure SARS-CoV-2 PCR testing experienced a higher reduction in the number of colonoscopies performed during the pandemic post-lockdown (34.0% reduction; 95% CI: 33.6%-34.4% vs. 13.7; 95% CI: 13.4%-13.9%) and in the number of CRCs diagnosed (34.1% reduction; 95% CI: 31.4%-36.8% vs. 26.7%; 95% CI: 24.6%-28.8%). Curative treatment was received by 87.5% of patients diagnosed with rectal cancer prepandemic and 80.7% of patients during the pandemic post-lockdown period (p = 0.002). CONCLUSIONS: The COVID-19 pandemic has led to a decrease in the number of diagnosed CRC cases and in the proportion of stage I CRC. The reduction in the number of colonoscopies and CRC diagnoses was higher in centers that applied universal SARS-CoV-2 PCR screening before colonoscopy. In addition, the COVID-19 pandemic has affected curative treatment of rectal cancers.


Assuntos
COVID-19 , Neoplasias Colorretais , Neoplasias Retais , Humanos , SARS-CoV-2 , COVID-19/epidemiologia , COVID-19/prevenção & controle , Pandemias , Estudos Prospectivos , Controle de Doenças Transmissíveis , Prognóstico , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Estudos Retrospectivos , Teste para COVID-19
6.
Front Sports Act Living ; 6: 1371467, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38463713

RESUMO

Introduction: The aims of this study were to compare several countermovement jump (CMJ) kinetic variables between professional (PRO) and semi-professional (SEMI-PRO) futsal players and examine the differences amongst playing positions. Methods: CMJ performance from 56 male futsal players (25.2 ± 4.8 years; weight: 74.4 ± 6.4 kg) was analysed. Players were separated into PRO (n = 29; 27.0 ± 4.4 years; 75.4 ± 6.0 kg) and SEMI-PRO (n = 27; 22.7 ± 4.3 years; 73.1 ± 6.8 kg), and according to playing position: defenders (n = 16; 25.4 ± 3.7 years; 75.2 ± 6.0 kg), wingers (n = 26; 23.5 ± 4.5 years; 72.0 ± 6.9 kg), and pivots (n = 14; 28.0 ± 5.6 years; 77.8 ± 4.3 kg). Linear mixed models and effect sizes were used for the analyses based on the mean of two jumps for each variable. Results: PRO players presented a deeper center of mass (COM) displacement (p = 0.002, ES = 0.83), greater eccentric (Ecc) absolute (p = 0.019, ES = 0.61) and relative peak power (p = 0.046, ES = 0.52), and achieved greater Ecc peak velocities (p = 0.004, ES = 0.76) when compared to SEMI-PRO. Non-significant and trivial-to-small differences were observed in all the other CMJ variables according to the competitive level and playing position. Discussion: Ecc capabilities (i.e., deeper COM displacement, greater Ecc absolute and relative peak power, and peak velocity) during vertical jump seem to differentiate PRO and SEMI-PRO players. However, CMJ variables do not discriminate amongst playing positions in futsal players.

7.
Neuropathol Appl Neurobiol ; 50(1): e12962, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38343067

RESUMO

AIMS: According to Braak's hypothesis, it is plausible that Parkinson's disease (PD) originates in the enteric nervous system (ENS) and spreads to the brain through the vagus nerve. In this work, we studied whether inflammatory bowel diseases (IBDs) in humans can progress with the emergence of pathogenic α-synuclein (α-syn) in the gastrointestinal tract and midbrain dopaminergic neurons. METHODS: We have analysed the gut and the ventral midbrain from subjects previously diagnosed with IBD and form a DSS-based rat model of gut inflammation in terms of α-syn pathology. RESULTS: Our data support the existence of pathogenic α-syn in both the gut and the brain, thus reinforcing the potential role of the ENS as a contributing factor in PD aetiology. Additionally, we have analysed the effect of a DSS-based rat model of gut inflammation to demonstrate (i) the appearance of P-α-syn inclusions in both Auerbach's and Meissner's plexuses (gut), (ii) an increase in α-syn expression in the ventral mesencephalon (brain) and (iii) the degeneration of nigral dopaminergic neurons, which all are considered classical hallmarks in PD. CONCLUSION: These results strongly support the plausibility of Braak's hypothesis and emphasise the significance of peripheral inflammation and the gut-brain axis in initiating α-syn aggregation and transport to the substantia nigra, resulting in neurodegeneration.


Assuntos
Doenças Inflamatórias Intestinais , Doença de Parkinson , Humanos , Ratos , Animais , alfa-Sinucleína/metabolismo , Doença de Parkinson/patologia , Encéfalo/patologia , Inflamação/patologia , Neurônios Dopaminérgicos/metabolismo , Doenças Inflamatórias Intestinais/patologia
8.
Waste Manag ; 178: 66-75, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38377770

RESUMO

On-site anaerobic digesters for small agricultural farms typically have feeding schedules that fluctuate according to farm operations. Shocks in feeding, particularly for putrescible waste can disrupt the stable operation of a digester. The effect of intermittent feeding on the anaerobic digestion of rejected raspberries was investigated in four 3L reactors operated in semicontinuous mode for 350 days at 38 °C with a hydraulic retention time of 25 days and an organic loading rate (OLR) of 1gVS/L/d. During the acclimatisation period (147 days) the organic loading was 5 feeds per week. The feeding regime of two reactors was then changed while maintaining the same OLR and HRT to one weekly feed event in one reactor and 3 equal feeds per week in another. The feeding regime did not significantly affect specific methane yield (369 ± 47 L/kgVS on average) despite very different weekly patterns in methane production. Volatile fatty acids (VFA) comprised >83 % of the organics in the effluent, while the rest included non-inhibitory concentrations of phenolic compounds (515-556 mg gallic acid/L). The microbial composition and relative abundance of predominant groups in all reactors were the archaeal genera Methanobacterium and Methanolinea and the bacterial phyla Bacteridota and Firmicutes. Increasing the OLR to 2gVS/L/d on day 238 resulted in failure of all reactors, attributed to the insufficient alkalinity to counterbalance the VFA produced, and the pH decrease below 6. Overall results suggests that optimal digestion of raspberry waste is maintained despite variations in feeding frequency, but acidification can occur with OLR changes.


Assuntos
Reatores Biológicos , Frutas , Anaerobiose , Reatores Biológicos/microbiologia , Ácidos Graxos Voláteis , Metano
9.
European J Pediatr Surg Rep ; 12(1): e16-e19, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38259259

RESUMO

Inguinal herniation of ureter is an uncommon finding among children, with scarce reported cases in the literature to date, that can potentially lead to obstructive uropathy. We report a case of ureteroinguinal herniation discovered during an inguinal hernia repair in a patient with antenatally ultrasound finding of hydronephrosis. A 2-month-old infant with antenatal left hydronephrosis presented with left inguinal mass. Preoperative ultrasound showed an anechoic tubular image producing a mass effect on the left testicle, with suspected bladder herniation and/or dilated ureter toward the inguinal canal. An open surgical inguinal exploration was performed, where the left inguinal canal revealed a peritoneal sac and sliding of the dilated left ureter behind the sac, with a significant change in diameter, corresponding to the paraperitoneal variant of ureteroinguinal herniation. Ligation of the sac and replacement of the ureter into the retroperitoneum were performed, with improvement in the hydronephrosis observed on the ultrasound 1 month after the intervention. However, 6 months later, hydronephrosis worsening as well as the obstructive pattern observed in the diuretic renogram required removal of the stenotic ureteral segment and reimplantation of the healthy proximal segment in the bladder by open approach (Cohen's reimplantation). Follow-up ultrasound of the renal tract showed no dilatation of the upper renal tract and the renal function tests were normal. Currently, the patient is 2 years old and he remains asymptomatic. In conclusion, s igns of ureteral obstruction such as hydronephrosis in patients with inguinal herniation may suggest the possibility of an ureteroinguinal hernia. Preoperative diagnostic suspicion is essential.

10.
Sensors (Basel) ; 23(23)2023 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-38067705

RESUMO

In the last decade there has been a growing interest in infrared thermography in the field of sports medicine in order to elucidate the mechanisms of thermoregulation. The aim of this study was to describe bilateral variations in skin temperature of the anterior thigh and patellar tendon in healthy athletes and to provide a model of baseline tendon and muscle thermoregulation in healthy sprinters following a unilateral isokinetic fatigue protocol. Fifteen healthy national-level sprinters (eleven men and four women), with at least 3 years of athletic training experience of 10-12 h/week and competing in national-level competitions, underwent unilateral isokinetic force testing and electrostimulation in which their body temperature was measured before, during, and after the protocol using an infrared thermographic camera. ANOVA detected a significant difference in the time × side interaction for patellar temperature changes (p ≤ 0.001) and a significant difference in the time/side interaction for quadriceps temperature changes (p ≤ 0.001). The thermal challenge produces homogeneous changes evident in quadriceps areas, but not homogeneous in tendon areas. These data show that metabolic and blood flow changes may depend on the physical and mechanical properties of each tissue. Future research could be conducted to evaluate the predictive value of neuromuscular fatigue in the patellar tendon and quadriceps after exercise in order to optimize post-exercise recovery strategies.


Assuntos
Ligamento Patelar , Tendões , Masculino , Humanos , Feminino , Músculo Quadríceps , Regulação da Temperatura Corporal , Exercício Físico
11.
Int J Mol Sci ; 24(24)2023 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-38139202

RESUMO

The presence of antiphospholipid antibodies (aPLs) is associated with antiphospholipid syndrome (APS), characterized by thrombosis and obstetric morbidity. aPLs included in APS classification criteria are lupus anticoagulant, anti-cardiolipin and anti-beta-2-glycoprotein-I of IgG or IgM isotypes. Enzyme-linked immunosorbent assay is the most used diagnostic technique to determine aPLs. Recently, new automated technologies mainly based in antigen-coated beads have been developed. The aim is to compare a fluorescence enzyme immunoassay (M1) and an antigen-coated bead assay (M2) in obstetric and thrombotic APS patients. All samples from the first 1020 patients received in the Immune Service Laboratory (Hospital 12 de Octubre) during the recruitment period, without exclusions, were analysed for aPLs. The weighted kappa for both methods in all the patients was 0.39 (0.30-0.47). Agreement increased to 0.56 (0.38-0.73) in patients with autoimmune disease. Sensitivity and specificity obtained for M1 were 17.1% and 89.3%, respectively, and 12.7% and 91.4% for M2. The sensibility and specificity of IgG isotypes were higher than the IgM ones. Regarding obstetric patients, M1 obtained significant diagnostic performance and had more sensitivity 23.75 (14.95-34.58) compared to M2 12.50 (6.16-21.79). In conclusion, clinical suspicion-based method selection for aPLs should be considered. To identify obstetric APS patients, solid phase methods remain more preferable.


Assuntos
Síndrome Antifosfolipídica , Trombose , Feminino , Gravidez , Humanos , Anticorpos Antifosfolipídeos , Inibidor de Coagulação do Lúpus , Imunoglobulina G , Imunoglobulina M
12.
mBio ; : e0249323, 2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-38032182

RESUMO

IMPORTANCE: Ergosterol is a critical membrane lipid in fungi. In Candida albicans, this essential plasma membrane amphipathic lipid is important for interactions with host cells, in particular, host immune responses. Here, we use a live-cell reporter for specifically visualizing ergosterol and show that apical enrichment of this sterol is not critical for budding and filamentous growth in this human fungal pathogen. Our results highlight that this live-cell reporter is likely to be a useful tool in the analyses of azole resistance and tolerance mechanisms, including alterations in drug targets and upregulation of efflux activities.

13.
Alzheimers Dement ; 2023 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-38018380

RESUMO

INTRODUCTION: Neuroinflammation is a major contributor to the progression of frontotemporal dementia (FTD). Galectin-3 (Gal-3), a microglial activation regulator, holds promise as a therapeutic target and potential biomarker. Our study aimed to investigate Gal-3 levels in patients with FTD and assess its diagnostic potential. METHODS: We examined Gal-3 levels in brain, serum, and cerebrospinal fluid (CSF) samples of patients with FTD and controls. Multiple linear regressions between Gal-3 levels and other FTD markers were explored. RESULTS: Gal-3 levels were increased significantly in patients with FTD, mainly across brain tissue and CSF, compared to controls. Remarkably, Gal-3 levels were higher in cases with tau pathology than TAR-DNA Binding Protein 43 (TDP-43) pathology. Only MAPT mutation carriers displayed increased Gal-3 levels in CSF samples, which correlated with total tau and 14-3-3. DISCUSSION: Our findings underscore the potential of Gal-3 as a diagnostic marker for FTD, particularly in MAPT cases, and highlights the relation of Gal-3 with neuronal injury markers.

14.
Opt Express ; 31(20): 33475-33485, 2023 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-37859129

RESUMO

In this work we perform a theoretical and simulation analysis of the behavior of an integrated four section distributed Bragg reflector semiconductor laser under optical injection and Q-switching operation. An electro-absorption modulator is introduced into the laser cavity to control the total losses and perform Q-switching. The simulations are done using a rate equation model. Q-switching operation produces very short and high power pulses. This, together with the use of optical injection, allows obtaining flat and broad optical frequency combs with up to 2100 optical lines within 10 dB (642 lines within 3 dB) at a repetition frequency of 100 MHz. The high chirp of the pulses is responsible for the broad spectra of these combs in comparison with gain switched combs, and the device structure allows fabrication in commercial foundries using standard building blocks.

15.
Waste Manag ; 169: 310-318, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37499411

RESUMO

Strawberry extrudate (SE) is an underused by-product from strawberry industry. Recovery of the phenolic compounds present in SE would represent a very interesting valorisation option. Two main challenges need to be solved, firstly, the solubilisation and recovery of the phenolic compounds contained in SE, and, after that, the stabilisation of the resulted de-phenolized SE. The present research evaluates the potential of a biorefinery process combining a hydrothermal pre-treatment, followed by a phenolic extraction process and, finally, the anaerobic digestion of the remaining SE for producing energy that will contribute to compensate the energy requirements of the whole system. Following the hydrothermal pre-treatment at 170 °C for 60 min, an extraction of 0.6 ± 0.1 g of gallic acid per kilogram of SE was achieved using an adsorbent resin, representing a recovery rate of 64 %. Long-term semi-continuous anaerobic digestion of de-phenolized SE was evaluated at different organic loading rates to evaluate the stability of the process. The anaerobic digestion of pre-treated SE achieved a stable methane production value of 243 ± 34 mL CH4·g volatile solids-1·d-1 at an organic loading rate (ORL) of 1.25 g volatile solids·L-1·d-1. During the operation at this ORL, the control parameters including pH, alkalinity, soluble chemical organic demand (sCOD), and volatile fatty acid (VFA) remained stable and consistently constant. Specifically, the VFA in the reactor during this stable period achieved a value of 102 ± 128 mg O2/L. Also, an economic balance showed that the minimal price of the generated phenolic extract for having benefited from the proposed biorefinery system was 0.812 €·(g of gallic acid equivalents)-1, a price within the range of phenolic compounds used in the food industry.


Assuntos
Fragaria , Anaerobiose , Reatores Biológicos , Metano
16.
Front Microbiol ; 14: 1224543, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37448576

RESUMO

Biological synthesis of high added-value compounds like adipic acid (AA), levulinic acid (LA), or polyhydroxybutyrate (PHB) using pure culture has been separately reported. However, pure culture requires sterile conditions and the use of specific carbon sources resulting in high operating costs. Different alternatives based on the use of mixed microbial cultures (MMC) have been explored to resolve this problem. MMC have been widely reported for the production of PHB, but scarcely reported for LA production and never for AA synthesis. This work presents a novel strategy for the co-production of AA LA, and PHB using MMC. The strategy consists in selecting an MMC producer of AA, LA and PHB from an inoculum obtained from a wastewater treatment plant, which is then subjected to the feast and famine culture strategy in a sequential batch reactor, coupled with a batch reactor step to enhance the accumulation of AA and LA. The results showed that the MMC could produce a 16 ± 2, 23 ± 1 and 5 ± %1 (g compound/g volatile solids) of AA, LA and PHB, respectively, using a non-fermented residual biomass rich in pentose, namely synthetic hemicellulose hydrolysate (SHH) as the carbon source. These results contribute to generating future research to better understand and optimise the biosynthesis of these compounds by MMC.

18.
J Pediatr Surg ; 58(11): 2149-2155, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37286413

RESUMO

AIM: Sarcopenia is associated with poor prognosis in adult oncologic patients, with little evidence of this association in pediatric population, including hepatoblastoma. METHODS: Retrospective study in patients with hepatoblastoma, divided into those with or without sarcopenia. Sarcopenia was assessed by measuring psoas muscle area (PMA) at L4-L5 level on the CT/MR and defined as z-score values ≤ 2. Relapse and mortality were analyzed. RESULTS: Twenty-one patients (57.1% male) were included, with median age 35.7 months (IQR: 23.5-58.5). Seven (33.3%) had sarcopenia on initial studies compared to 14 (66.7%) who did not. No differences were found between groups in age, weight, PRETEXT, surgical treatment or. α-fetoprotein levels. Sarcopenia was associated with a higher rate of metastases at diagnosis (49.2% vs 0.0%; p = 0.026) and surgical complications (57.1% vs 21.4%, p = 0.047). After a median follow-up of 65.1 months (1.7-144.8), 2 patients (28.6%) had tumor relapse in sarcopenic group compared to 1 (7.1%) in non-sarcopenic group. Two patients died in sarcopenic group and 1 in non-sarcopenic group. Median event-free survival (EFS) was lower in sarcopenic group (100.38 ± 25.63 vs 118.91 ± 11.52 months) as well as overall survival (OS) (101.72 ± 24.86 vs 121.78 ± 8.75 months) with no statistical significance. Five-year EFS was also lower in sarcopenic group (71% vs 93%) as well as 5-year OS (71% vs 87%). CONCLUSIONS: Sarcopenia at diagnosis was associated with a higher rate of metastases and surgical complications in hepatoblastoma. Our data shows the first evidence of its role as a possible poor prognostic factor, influencing survival and risk of relapse. LEVEL OF EVIDENCE: II. TYPE OF STUDY: Original article. Retrospective study.

20.
Acta Neuropathol ; 146(1): 51-75, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37202527

RESUMO

Parkinson's Disease (PD) is a neurodegenerative and progressive disorder characterised by intracytoplasmic inclusions called Lewy bodies (LB) and degeneration of dopaminergic neurons in the substantia nigra (SN). Aggregated α-synuclein (αSYN) is known to be the main component of the LB. It has also been reported to interact with several proteins and organelles. Galectin-3 (GAL3) is known to have a detrimental function in neurodegenerative diseases. It is a galactose-binding protein without known catalytic activity and is expressed mainly by activated microglial cells in the central nervous system (CNS). GAL3 has been previously found in the outer layer of the LB in post-mortem brains. However, the role of GAL3 in PD is yet to be elucidated. In post-mortem samples, we identified an association between GAL3 and LB in all the PD subjects studied. GAL3 was linked to less αSYN in the LB outer layer and other αSYN deposits, including pale bodies. GAL3 was also associated with disrupted lysosomes. In vitro studies demonstrate that exogenous recombinant Gal3 is internalised by neuronal cell lines and primary neurons where it interacts with endogenous αSyn fibrils. In addition, aggregation experiments show that Gal3 affects spatial propagation and the stability of pre-formed αSyn fibrils resulting in short, amorphous toxic strains. To further investigate these observations in vivo, we take advantage of WT and Gal3KO mice subjected to intranigral injection of adenovirus overexpressing human αSyn as a PD model. In line with our in vitro studies, under these conditions, genetic deletion of GAL3 leads to increased intracellular αSyn accumulation within dopaminergic neurons and remarkably preserved dopaminergic integrity and motor function. Overall, our data suggest a prominent role for GAL3 in the aggregation process of αSYN and LB formation, leading to the production of short species to the detriment of larger strains which triggers neuronal degeneration in a mouse model of PD.


Assuntos
Galectina 3 , Doença de Parkinson , Animais , Humanos , Camundongos , alfa-Sinucleína/metabolismo , Neurônios Dopaminérgicos/metabolismo , Galectina 3/metabolismo , Corpos de Lewy/metabolismo , Doença de Parkinson/metabolismo
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