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1.
Bioprocess Biosyst Eng ; 47(6): 767-839, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38643271

RESUMO

Since cardiovascular diseases (CVDs) are globally one of the leading causes of death, of which myocardial infarction (MI) can cause irreversible damage and decrease survivors' quality of life, novel therapeutics are needed. Current approaches such as organ transplantation do not fully restore cardiac function or are limited. As a valuable strategy, tissue engineering seeks to obtain constructs that resemble myocardial tissue, vessels, and heart valves using cells, biomaterials as scaffolds, biochemical and physical stimuli. The latter can be induced using a bioreactor mimicking the heart's physiological environment. An extensive review of bioreactors providing perfusion, mechanical and electrical stimulation, as well as the combination of them is provided. An analysis of the stimulations' mechanisms and modes that best suit cardiac construct culture is developed. Finally, we provide insights into bioreactor configuration and culture assessment properties that need to be elucidated for its clinical translation.


Assuntos
Reatores Biológicos , Estimulação Elétrica , Engenharia Tecidual , Engenharia Tecidual/métodos , Humanos , Animais , Perfusão , Miocárdio/metabolismo , Alicerces Teciduais/química
2.
Toxins (Basel) ; 16(4)2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38668589

RESUMO

Coralsnakes (Micrurus spp.) are the only elapids found throughout the Americas. They are recognized for their highly neurotoxic venom, which is comprised of a wide variety of toxins, including the stable, low-mass toxins known as three-finger toxins (3FTx). Due to difficulties in venom extraction and availability, research on coralsnake venoms is still very limited when compared to that of other Elapidae snakes like cobras, kraits, and mambas. In this study, two previously described 3FTx from the venom of M. corallinus, NXH1 (3SOC1_MICCO), and NXH8 (3NO48_MICCO) were characterized. Using in silico, in vitro, and ex vivo experiments, the biological activities of these toxins were predicted and evaluated. The results showed that only NXH8 was capable of binding to skeletal muscle cells and modulating the activity of nAChRs in nerve-diaphragm preparations. These effects were antagonized by anti-rNXH8 or antielapidic sera. Sequence analysis revealed that the NXH1 toxin possesses eight cysteine residues and four disulfide bonds, while the NXH8 toxin has a primary structure similar to that of non-conventional 3FTx, with an additional disulfide bond on the first loop. These findings add more information related to the structural diversity present within the 3FTx class, while expanding our understanding of the mechanisms of the toxicity of this coralsnake venom and opening new perspectives for developing more effective therapeutic interventions.


Assuntos
Clonagem Molecular , Cobras Corais , Venenos Elapídicos , Músculo Esquelético , Receptores Nicotínicos , Animais , Venenos Elapídicos/química , Venenos Elapídicos/toxicidade , Venenos Elapídicos/genética , Receptores Nicotínicos/metabolismo , Receptores Nicotínicos/genética , Músculo Esquelético/metabolismo , Músculo Esquelético/efeitos dos fármacos , Sequência de Aminoácidos , Masculino
3.
Biotechnol Bioeng ; 121(6): 1789-1802, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38470342

RESUMO

Decoupling cell formation from recombinant protein synthesis is a potent strategy to intensify bioprocesses. Escherichia coli strains with mutations in the glucose uptake components lack catabolite repression, display low growth rate, no overflow metabolism, and high recombinant protein yields. Fast growth rates were promoted by the simultaneous consumption of glucose and glycerol, and this was followed by a phase of slow growth, when only glucose remained in the medium. A glycerol-repressible genetic circuit was designed to autonomously induce recombinant protein expression. The engineered strain bearing the genetic circuit was cultured in 3.9 g L-1 glycerol + 18 g L-1 glucose in microbioreactors with online oxygen transfer rate monitoring. The growth was fast during the simultaneous consumption of both carbon sources (C-sources), while expression of the recombinant protein was low. When glycerol was depleted, the growth rate decreased, and the specific fluorescence reached values 17% higher than those obtained with a strong constitutive promoter. Despite the relatively high amount of C-source used, no oxygen limitation was observed. The proposed approach eliminates the need for the substrate feeding or inducers addition and is set as a simple batch culture while mimicking fed-batch performance.


Assuntos
Escherichia coli , Glucose , Glicerol , Proteínas Recombinantes , Glicerol/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Escherichia coli/crescimento & desenvolvimento , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/biossíntese , Glucose/metabolismo , Reatores Biológicos , Redes Reguladoras de Genes , Engenharia Metabólica/métodos , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo
4.
Toxics ; 12(2)2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38393244

RESUMO

Several epidemiological studies have demonstrated that particulate matter (PM) in air pollution can be involved in the genesis or aggravation of different cardiovascular, respiratory, perinatal, and cancer diseases. This study assessed the in vitro effects of PM10 on the secretion of cytokines by a human monocytic cell line (THP-1). We compared the chemotactic, pro-inflammatory, and anti-inflammatory cytokines induced by PM10 collected for two years during three different seasons in five different Mexico City locations. MIP-1α, IP-10, MCP-1, TNF-α, and VEGF were the main secretion products after stimulation with 80 µg/mL of PM10 for 24 h. The THP-1 cells showed a differential response to PM10 obtained in the different sites of Mexico City. The PM10 from the north and the central city areas induced a higher pro-inflammatory cytokine response than those from the south. Seasonal pro-inflammatory cytokine secretion always exceeded anti-inflammatory secretion. The rainy-season-derived particles caused the lowest pro-inflammatory effects. We concluded that toxicological assessment of airborne particles provides evidence supporting their potential role in the chronic exacerbation of local or systemic inflammatory responses that may worsen the evolution of some chronic diseases.

5.
Microorganisms ; 12(1)2024 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-38257977

RESUMO

The demand of plasmid DNA (pDNA) as a key element for gene therapy products, as well as mRNA and DNA vaccines, is increasing together with the need for more efficient production processes. An engineered E. coli strain lacking the phosphotransferase system and the pyruvate kinase A gene has been shown to produce more pDNA than its parental strain. With the aim of improving pDNA production in the engineered strain, several strategies to increase the flux to the pentose phosphate pathway (PPP) were evaluated. The simultaneous consumption of glucose and glycerol was a simple way to increase the growth rate, pDNA production rate, and supercoiled fraction (SCF). The overexpression of key genes from the PPP also improved pDNA production in glucose, but not in mixtures of glucose and glycerol. Particularly, the gene coding for the glucose 6-phosphate dehydrogenase (G6PDH) strongly improved the SCF, growth rate, and pDNA production rate. A linear relationship between the G6PDH activity and pDNA yield was found. A higher flux through the PPP was confirmed by flux balance analysis, which also estimates relevant differences in fluxes of the tricarboxylic acid cycle. These results are useful for developing further cell engineering strategies to increase pDNA production and quality.

6.
Biotechnol Bioeng ; 121(4): 1216-1230, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38178599

RESUMO

Industrial cultures are hindered by the physiological complexity of the host and the limited mass transfer capacity of conventional bioreactors. In this study, a minimal cell approach was combined with genetic devices to overcome such issues. A flavin mononucleotide-based fluorescent protein (FbFP) was expressed in a proteome-reduced Escherichia coli (PR). When FbFP was expressed from a constitutive protein generator (CPG), the PR strain produced 47% and 35% more FbFP than its wild type (WT), in aerobic or oxygen-limited regimes, respectively. Metabolic and expression models predicted more efficient biomass formation at higher fluxes to FbFP, in agreement with these results. A microaerobic protein generator (MPG) and a microaerobic transcriptional cascade (MTC) were designed to induce FbFP expression upon oxygen depletion. The FbFP fluorescence using the MTC in the PR strain was 9% higher than that of the WT bearing the CPG under oxygen limitation. To further improve the PR strain, the pyruvate dehydrogenase complex regulator gene was deleted, and the Vitreoscilla hemoglobin was expressed. Compared to oxygen-limited cultures of the WT, the engineered strains increased the FbFP expression more than 50% using the MTC. Therefore, the designed expression systems can be a valuable alternative for industrial cultivations.


Assuntos
Oxigênio , Proteoma , Proteoma/genética , Proteoma/metabolismo , Oxigênio/metabolismo , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Reatores Biológicos
7.
Can J Neurol Sci ; 51(2): 289-292, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37519226

RESUMO

Exposure to industrial pollutants is a potential risk factor not fully explored in ASD with regression (ASD+R). We studied geographical collocation patterns of industrial air chemical emissions and the location of homes of children with ASD+R at different exposure times, compared with ASD cases without regression (ASD-R). Fifteen of 111 emitted chemicals collocated with ASD+R, and 65 with ASD-R. ASD+R collocated more strongly with different neurotoxicants/immunotoxicants a year before diagnosis, whereas ASD-R were moderately collocated with chemicals across all exposure periods. This preliminary exploratory analysis of differences in exposure patterns raises a question regarding potential pathophysiological differences between the conditions.


Assuntos
Poluentes Atmosféricos , Transtorno do Espectro Autista , Transtorno Autístico , Criança , Humanos , Poluentes Atmosféricos/análise , Fatores de Risco , Razão de Chances , Exposição Ambiental/efeitos adversos
8.
J Endocrinol Invest ; 47(4): 795-818, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37921990

RESUMO

PURPOSE: Since vertebral fragility fractures (VFFs) might increase the risk of subsequent fractures, we evaluated the incidence rate and the refracture risk of subsequent vertebral and non-vertebral fragility fractures (nVFFs) in untreated patients with a previous VFF. METHODS: We systematically searched PubMed, Embase, and Cochrane Library up to February 2022 for randomized clinical trials (RCTs) that analyzed the occurrence of subsequent fractures in untreated patients with prior VFFs. Two authors independently extracted data and appraised the risk of bias in the selected studies. Primary outcomes were subsequent VFFs, while secondary outcomes were further nVFFs. The outcome of refracture within ≥ 2 years after the index fracture was measured as (i) rate, expressed per 100 person-years (PYs), and (ii) risk, expressed in percentage. RESULTS: Forty RCTs met our inclusion criteria, ranging from medium to high quality. Among untreated patients with prior VFFs, the rate of subsequent VFFs and nVFFs was 12 [95% confidence interval (CI) 9-16] and 6 (95% CI 5-8%) per 100 PYs, respectively. The higher the number of previous VFFs, the higher the incidence. Moreover, the risk of VFFs and nVFFs increased within 2 (16.6% and 8%) and 4 years (35.1% and 17.4%) based on the index VFF. CONCLUSION: The highest risk of subsequent VFFs or nVFFs was already detected within 2 years following the initial VFF. Thus, prompt interventions should be designed to improve the detection and treatment of VFFs, aiming to reduce the risk of future FFs and properly implement secondary preventive measures.


Assuntos
Fraturas Ósseas , Fraturas por Osteoporose , Fraturas da Coluna Vertebral , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Fraturas da Coluna Vertebral/etiologia , Coluna Vertebral
9.
Curr Issues Mol Biol ; 45(12): 10131-10158, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38132479

RESUMO

The embryonic development of neural crest cells and subsequent tissue differentiation are intricately regulated by specific transcription factors. Among these, SOX10, a member of the SOX gene family, stands out. Located on chromosome 22q13, the SOX10 gene encodes a transcription factor crucial for the differentiation, migration, and maintenance of tissues derived from neural crest cells. It plays a pivotal role in developing various tissues, including the central and peripheral nervous systems, melanocytes, chondrocytes, and odontoblasts. Mutations in SOX10 have been associated with congenital disorders such as Waardenburg-Shah Syndrome, PCWH syndrome, and Kallman syndrome, underscoring its clinical significance. Furthermore, SOX10 is implicated in neural and neuroectodermal tumors, such as melanoma, malignant peripheral nerve sheath tumors (MPNSTs), and schwannomas, influencing processes like proliferation, migration, and differentiation. In mesenchymal tumors, SOX10 expression serves as a valuable marker for distinguishing between different tumor types. Additionally, SOX10 has been identified in various epithelial neoplasms, including breast, ovarian, salivary gland, nasopharyngeal, and bladder cancers, presenting itself as a potential diagnostic and prognostic marker. However, despite these associations, further research is imperative to elucidate its precise role in these malignancies.

11.
Dalton Trans ; 52(44): 16356-16363, 2023 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-37861654

RESUMO

Successful synthesis has been reported of 4-Mes2B-3,5-(CF3)2PzH and 4-Mes2B-3,5-(CF3)2PzH bearing sterically demanding diarylboron moieties at the pyrazole ring 4-position, and their corresponding copper(I) pyrazolate complexes. They show visible blue photoluminescence in solution. The X-ray crystal structures revealed that the fluorinated {[4-BMes2-3,5-(CF3)2Pz]Cu}3 crystallizes as discrete trinuclear molecules whereas as the non-fluorinated {[4-BMes2-3,5-(CH3)2Pz]Cu}3 forms dimers of trimers with two close inter-trimer Cu⋯Cu separations. The solid {[4-BMes2-3,5-(CF3)2Pz]Cu}3 featuring a sterically confined Cu3N6 core displays bright blue phosphorescence while {[4-BMes2-3,5-(CH3)2Pz]Cu}3, which is a dimer of a trimer, is a red phosphor at room temperature. This work illustrates the modulation of photo-physical properties of metal pyrazolates by adjusting the supporting ligand steric features and introducing secondary diarylboron luminophores. Computational analysis of the structures and photophysical properties of copper complexes are also presented.

12.
Viruses ; 15(9)2023 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-37766248

RESUMO

(1) Background: COVID-19 has evolved during seven epidemic waves in Spain. Our objective was to describe changes in mortality and severity in our hospitalized patients. (2) Method: This study employed a descriptive, retrospective approach for COVID-19 patients admitted to the Hospital de Fuenlabrada (Madrid, Spain) until 31 December 2022. (3) Results: A total of 5510 admissions for COVID-19 were recorded. The first wave accounted for 1823 (33%) admissions and exhibited the highest proportion of severe patients: 65% with bilateral pneumonia and 83% with oxygen saturation under 94% during admission and elevated levels of CRP, IL-6, and D-dimer. In contrast, the seventh wave had the highest median age (79 years) and comorbidity (Charlson: 2.7), while only 3% of patients had bilateral pneumonia and 3% required intubation. The overall mortality rate was 10.3%. The first wave represented 39% of the total. The variables related to mortality were age (OR: 1.08, 1.07-1.09), cancer (OR: 1.99, 1.53-2.60), dementia (OR: 1.82, 1.20-2.75), the Charlson index (1.38, 1.31-1.47), the need for high-flow oxygen (OR: 6.10, 4.94-7.52), mechanical ventilation (OR: 11.554, 6.996-19.080), and CRP (OR: 1.04, 1.03-1.06). (4) Conclusions: The variables associated with mortality included age, comorbidity, respiratory failure, and inflammation. Differences in the baseline characteristics of admitted patients explained the differences in mortality in each wave. Differences observed between patients admitted in the latest wave and the earlier ones suggest that COVID-19 has evolved into a distinct disease, requiring a distinct approach.


Assuntos
COVID-19 , Epidemias , Humanos , Idoso , COVID-19/epidemiologia , Estudos Retrospectivos , Hospitais , Hospitalização
13.
Arch Osteoporos ; 18(1): 109, 2023 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-37603196

RESUMO

Randomized clinical trials and observational studies on the implementation of clinical governance models, in patients who had experienced a fragility fracture, were examined. Literature was systematically reviewed and summarized by a panel of experts who formulated recommendations for the Italian guideline. PURPOSE: After experiencing a fracture, several strategies may be adopted to reduce the risk of recurrent fragility fractures and associated morbidity and mortality. Clinical governance models, such as the fracture liaison service (FLS), have been introduced for the identification, treatment, and monitoring of patients with secondary fragility fractures. A systematic review was conducted to evaluate the association between multidisciplinary care systems and several outcomes in patients with a fragility fracture in the context of the development of the Italian Guidelines. METHODS: PubMed, Embase, and the Cochrane Library were investigated up to December 2020 to update the search of the Scottish Intercollegiate Guidelines Network. Randomized clinical trials (RCTs) and observational studies that analyzed clinical governance models in patients who had experienced a fragility fracture were eligible. Three authors independently extracted data and appraised the risk of bias in the included studies. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation methodology. Effect sizes were pooled in a meta-analysis using random-effects models. Primary outcomes were bone mineral density values, antiosteoporotic therapy initiation, adherence to antiosteoporotic medications, subsequent fracture, and mortality risk, while secondary outcomes were quality of life and physical performance. RESULTS: Fifteen RCTs and 62 observational studies, ranging from very low to low quality for bone mineral density values, antiosteoporotic initiation, adherence to antiosteoporotic medications, subsequent fracture, mortality, met our inclusion criteria. The implementation of clinical governance models compared to their pre-implementation or standard care/non-attenders significantly improved BMD testing rate, and increased the number of patients who initiated antiosteoporotic therapy and enhanced their adherence to the medications. Moreover, the treatment by clinical governance model respect to standard care/non-attenders significantly reduced the risk of subsequent fracture and mortality. The integrated structure of care enhanced the quality of life and physical function among patients with fragility fractures. CONCLUSIONS: Based on our findings, clinicians should promote the management of patients experiencing a fragility fracture through structured and integrated models of care. The task force has formulated appropriate recommendations on the implementation of multidisciplinary care systems in patients with, or at risk of, fragility fractures.


Assuntos
Governança Clínica , Fraturas Ósseas , Humanos , Pessoa de Meia-Idade , Fraturas Ósseas/prevenção & controle , Densidade Óssea , Comitês Consultivos , Desempenho Físico Funcional
14.
Heliyon ; 9(8): e19021, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37600413

RESUMO

Immobilization of enzymes is one of the protein engineering methods used to improve their thermal and long-term stabilities. Immobilized pectinase has become an essential biocatalyst for optimization in the food processing industry. Herein, nanostructured magnetic nanoparticles were prepared in situ for use as supports to immobilize pectinase. The structural, morphological, optical and magnetic features and the chemical compositions of the nanoparticles were characterized. Nanoparticle agglomeration and low porosity were observed due to the synthetic conditions. These nanoparticles exhibited superparamagnetic behavior, which is desirable for biotechnological applications. The maximum retention rate for the enzyme was observed at pH 4.5 with a value of 1179.3 U/mgNP (units per milligram of nanoparticle), which was equivalent to a 65.6% efficiency. The free and immobilized pectinase were affected by the pH and temperature. The long-term instability caused 40% and 32% decreases in the specific activities of the free and immobilized pectinase, respectively. The effects of immobilization were analyzed with kinetic and thermodynamic studies. These results indicated a significant affinity for the substrate, a decreased reaction rate, and improved thermal stability of the immobilized pectinase. The reusability of the immobilized pectinase was preserved effectively during cycling, with only a 21.2% decrease in activity observed from the first to the last use. Therefore, alternative magnetic nanoparticles are presented for immobilizing and maintaining the thermostability of pectinase.

15.
Materials (Basel) ; 16(14)2023 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-37512358

RESUMO

Plasterboard is an important building material in the construction industry because it allows for quick installation of walls, partitions, and ceilings. Although a common material, knowledge about its performance related to modern polymers and fabrication conditions is still lacking. The present work analyzes how some manufacturing factors applied during the plaster board fabrication impact on some plasterboard properties, including water absorption, flexural strength, and thermal conductivity. The manufacturing variables evaluated are the dose (D) of polymethylhydrosiloxane (PMHS), the agitation time of the mixture (H), and the drying temperature of the plaster boards after setting (T). The results suggest that factors D, H, and T induce changes in the porosity and the morphological structure of the calcium sulfate dihydrate crystals formed. Performance is evaluated at two levels of each factor following a statistical method of factorial experimental design centered on a cube. Morphological changes in the crystals of the resulting boards were evaluated with scanning electron microscopy (SEM) and the IMAGEJ image analysis program. Porosity changes were evaluated with X-ray microcomputed tomography (XMT) and 3D image analysis tools. The length-to-width ratio of the crystals decreases as it goes from low PMHS dosage to high dosage, favoring a better compaction of the plasterboard under the right stirring time and drying temperature. In contrast, the porosity generated by the incorporation of PMHS increases when going from low-level to high-level conditions and affects the maximum size of the pores being generated, with a maximum value achieved at 0.6% dosage, 40 s, and 140 °C conditions. The presence of an optimal PMHS dosage value that is approximately 0.6-1.0% is evidenced. In fact, when comparing trails without and with PMHS addition, a 10% decrease in thermal conductivity is achieved at high H (60 s) and high T (150 °C) level conditions. Water absorption decreases by more than 90% when PMHS is added, mainly due to the hydrophobic action of the PMHS. Minimum water absorption levels can be obtained at high drying temperatures. Finally, the resistance to flexion is not affected by the addition of PMHS because apparently there are two opposing forces acting: on one hand is the decrease in the length-width ratio giving more compactness, and on the other hand is the generation of pores. The maximum resistance to flexion was found around a dosage of 0.6% PMHS. In conclusion, the results suggest that the addition of PMHS, the correct agitation time of the mixture, and the drying temperature reduce the water absorption and the thermal conductivity of the gypsum boards, with no significant changes in the flexural resistance.

16.
Bioengineering (Basel) ; 10(7)2023 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-37508835

RESUMO

The bacterium Escherichia coli is a widely used organism in biotechnology. For high space-time yields, glucose-limited fed-batch technology is the industry standard; this is because an overflow metabolism of acetate occurs at high glucose concentrations. As an interesting alternative, various strains with limited glucose uptake have been developed. However, these have not yet been characterized under process conditions. To demonstrate the efficiency of our previously developed high-throughput robotic platform, in the present work, we characterized three different exemplary E. coli knockout (KO) strains with limited glucose uptake capacities at three different scales (microtiter plates, 10 mL bioreactor system and 100 mL bioreactor system) under excess glucose conditions with different initial glucose concentrations. The extensive measurements of growth behavior, substrate consumption, respiration, and overflow metabolism were then used to determine the appropriate growth parameters using a mechanistic mathematical model, which allowed for a comprehensive comparative analysis of the strains. The analysis was performed coherently with these different reactor configurations and the results could be successfully transferred from one platform to another. Single and double KO mutants showed reduced specific rates for substrate uptake qSmax and acetate production qApmax; meanwhile, higher glucose concentrations had adverse effects on the biomass yield coefficient YXSem. Additional parameters compared to previous studies for the oxygen uptake rate and carbon dioxide production rate indicated differences in the specific oxygen uptake rate qOmax. This study is an example of how automated robotic equipment, together with mathematical model-based approaches, can be successfully used to characterize strains and obtain comprehensive information more quickly, with a trade-off between throughput and analytical capacity.

17.
Int J Mol Sci ; 24(14)2023 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-37511161

RESUMO

This study takes a step in understanding the physiological implications of the nanosecond pulsed electric field (nsPEF) by integrating molecular dynamics simulations and machine learning techniques. nsPEF, a state-of-the-art technology, uses high-voltage electric field pulses with a nanosecond duration to modulate cellular activity. This investigation reveals a relatively new and underexplored phenomenon: protein-mediated electroporation. Our research focused on the voltage-sensing domain (VSD) of the NaV1.5 sodium cardiac channel in response to nsPEF stimulation. We scrutinized the VSD structures that form pores and thereby contribute to the physical chemistry that governs the defibrillation effect of nsPEF. To do so, we conducted a comprehensive analysis involving the clustering of 142 replicas simulated for 50 ns under nsPEF stimuli. We subsequently pinpointed the representative structures of each cluster and computed the free energy between them. We find that the selected VSD of NaV1.5 forms pores under nsPEF stimulation, but in a way that significant differs from the traditional VSD opening. This study not only extends our understanding of nsPEF and its interaction with protein channels but also adds a new effect to further study.


Assuntos
Eletricidade , Eletroporação , Eletroporação/métodos , Terapia com Eletroporação , Coração
18.
J Endocrinol Invest ; 46(11): 2287-2297, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37031450

RESUMO

PURPOSE: Preventing fragility fractures by treating osteoporosis may reduce disability and mortality worldwide. Algorithms combining clinical risk factors with bone mineral density have been developed to better estimate fracture risk and possible treatment thresholds. This systematic review supported panel members of the Italian Fragility Fracture Guidelines in recommending the use of best-performant tool. The clinical performance of the three most used fracture risk assessment tools (DeFRA, FRAX, and FRA-HS) was assessed in at-risk patients. METHODS: PubMed, Embase, and Cochrane Library were searched till December 2020 for studies investigating risk assessment tools for predicting major osteoporotic or hip fractures in patients with osteoporosis or fragility fractures. Sensitivity (Sn), specificity (Sp), and areas under the curve (AUCs) were evaluated for all tools at different thresholds. Quality assessment was performed using the Quality Assessment of Diagnostic Accuracy Studies-2; certainty of evidence (CoE) was evaluated using the Grading of Recommendations Assessment, Development and Evaluation approach. RESULTS: Forty-three articles were considered (40, 1, and 2 for FRAX, FRA-HS, and DeFRA, respectively), with the CoE ranging from very low to high quality. A reduction of Sn and increase of Sp for major osteoporotic fractures were observed among women and the entire population with cut-off augmentation. No significant differences were found on comparing FRAX to DeFRA in women (AUC 59-88% vs. 74%) and diabetics (AUC 73% vs. 89%). FRAX demonstrated non-significantly better discriminatory power than FRA-HS among men. CONCLUSION: The task force formulated appropriate recommendations on the use of any fracture risk assessment tools in patients with or at risk of fragility fractures, since no statistically significant differences emerged across different prediction tools.


Assuntos
Osteoporose , Fraturas por Osteoporose , Masculino , Humanos , Feminino , Osteoporose/diagnóstico , Fraturas por Osteoporose/diagnóstico , Fraturas por Osteoporose/epidemiologia , Fraturas por Osteoporose/etiologia , Densidade Óssea , Fatores de Risco , Medição de Risco
19.
Inflammation ; 46(1): 388-403, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36171491

RESUMO

Both periodontal disease (PD) and metabolic syndrome (MS) represent disorders of concern worldwide. Current evidence indicates that PD and MS might negatively influence each other, increasing the risk for cardiovascular diseases (CVD), via mutual inflammatory pathways. A failure of the inflammation resolution mechanisms is crucial for these comorbidities. Fish oil-derived omega-3 has been linked with resolution-driven responses in different pathological conditions during the last years. This study evaluated the impacts of omega-3 supplementation in a rat model combining ligature-induced PD and 10% fructose intake-elicited MS. Our main findings show that 10% fructose ingestion led to an elevation of Lee index and white adipose tissue (WAT) weight, along with hepatic alterations, accompanied by an increase of leptin, and a decrement of adiponectin serum amounts, regardless of PD induction. Noteworthy, the co-induction of PD and MS resulted in higher levels of glycemia and triglycerides, being this latter effect lessened by omega-3 supplementation. In this case, the beneficial effects of omega-3 might be associated with its ability to recover the decline of serum adiponectin levels in rats with PD plus MS. As expected, PD induction led to alveolar bone loss, independent of MS induction. However, the supplementation with omega-3 restored alveolar bone in PD control animals, but not in the rats with PD combined with MS. Our study extends the knowledge about PD and MS as comorbidities, showing novel effects of omega-3 supplementation in this context.


Assuntos
Ácidos Graxos Ômega-3 , Síndrome Metabólica , Doenças Periodontais , Periodontite , Ratos , Animais , Síndrome Metabólica/tratamento farmacológico , Adiponectina , Frutose/efeitos adversos , Ácidos Graxos Ômega-3/farmacologia , Ácidos Graxos Ômega-3/uso terapêutico , Periodontite/metabolismo
20.
Heliyon ; 8(10): e10811, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36203903

RESUMO

Background and objectives: Climate change impacts are felt unequally worldwide; populations that experience geographical vulnerability, those living in small island states and densely populated coastal areas, and children and women are affected disproportionately. This scoping review aims to synthesize evidence from relevant studies centred on South Asia, identify research gaps specifically focused on children and women's health, and contribute to knowledge about South Asia's existing mitigation and adaptation strategies. Methods: A research librarian executed the search on six databases using controlled vocabulary (e.g., MeSH, Emtree, etc.) and keywords representing the concepts "vulnerable populations" and "climate change" and "health impacts" and "South Asia." Databases were searched from January 2010 to May 2020. Papers were screened independently by two researchers. Results: Forty-two studies were included, of which 23 were based in India, 14 in Bangladesh, and five in other South Asian countries. Nineteen studies focused on meteorological factors as the primary exposure. In contrast, thirteen focused on extreme weather events, nine on air pollution, and one on salinity in coastal areas. Thirty-four studies focused on the health impacts on children related to extreme weather events, meteorological factors, and air pollution, while only eight studies looked at health impacts on women. Undernutrition, ARI (acute respiratory infection), diarrheal diseases, low birth weight, and premature mortality were the major health impacts attributed to extreme weather events, meteorological factors, and air pollution exposure in children and women in the region. Conclusion: Extreme weather events, meteorological factors and air pollution have affected the health of children and women in South Asia. However, the gap in the literature across the South Asian countries concerning relationships between exposure to extreme weather events, meteorological factors, air pollution and health effects, including mental health problems in children and women, are opportunities for future work.

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