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1.
Dent Traumatol ; 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38576382

RESUMO

BACKGROUND/AIM: This study assessed the epidemiology of luxation injuries with or without dental fractures in patients attending the outpatient clinic of a Brazilian dental school over the past decade. MATERIAL AND METHODS: We reviewed clinical records from a specialized center for dental trauma care in Brazil, focusing on patients who experienced at least one traumatic dental injury (TDI) in a permanent tooth between 2012 and 2022. The extracted data included sex, age, etiology, time between trauma occurrence and the search for initial care, TDI classification, and the need for endodontic treatment. The statistical analysis involved Pearson's chi-squared and Fisher's exact tests at a 5% significance level. RESULTS: The 366 analyzed clinical records included 166 patients (350 teeth) with luxation injuries. Men (n = 102) showed a higher prevalence of luxation injuries than women (n = 64). Extrusive luxation prevailed (n = 99 patients and 208 teeth). Patients with luxation injuries sought care promptly after dental trauma incidents (p = .02) and demonstrated a higher incidence of endodontic treatment (p < .0001) than those without luxation injuries. Lateral luxation was notably associated with traffic accidents (p < .0001). The combination of luxation injuries and tooth fractures did not correlate with a higher need for endodontic treatment (p > .05). CONCLUSIONS: Age and trauma etiology seemed to have influenced the epidemiological profile of luxation injuries. Additionally, these injuries affected the time to seek initial care and the need for endodontic treatment.

2.
Eur J Clin Invest ; : e14218, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38629697

RESUMO

Adolphe Quételet, a 19th-century Belgian sociologist and statistician, pioneered the incorporation of statistics into social sciences. He initiated the development of anthropometry since he was interested in identifying the proportions of the 'ideal man'. He devised a ratio between weight and height, originally termed the Quételet Index, and today widely known and used as the body mass index or BMI. In 1835, he demonstrated that a normal curve accommodates the distribution of human traits articulating his reasoning on human variance around the average. Quételet's long-lasting legacy of the establishment of a simple measure to classify people's weight relative to an ideal for their height endures today with minor variations having dramatically influenced public health agendas. While being very useful, the limitations of the BMI are well known. Thus, revisiting the beyond BMI paradigm is a necessity in the era of precision medicine with morphofunctional assessment representing the way forward via incorporation of body composition and functionality appraisal. While healthcare systems were originally designed to address acute illnesses, today's demands require a radical rethinking together with an original reappraisal of our diagnosis and treatment approaches from a multidimensional perspective. Embracing new methodologies is the way forward to advance the field, gain a closer look at the underlying pathophysiology of excess weight, keep the spotlight on improving diagnostic performance and demonstrate its clinical validity. In order to provide every patient with the most accurate diagnosis together with the most appropriate management, a high degree of standardization and personalization is needed.

3.
Polymers (Basel) ; 16(7)2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38611137

RESUMO

In this work, hybrid materials within the polydimethylsiloxane-silica (PDMS-SiO2) system, synthesized via the sol-gel method, were developed and characterized for their potential to incorporate and release the bioactive compound resveratrol (RES). RES was incorporated into the materials with a high loading efficiency (>75%) using the rotary evaporator technique. This incorporation induced the amorphization of RES, resulting in enhanced solubility and in vitro release when compared to the free polyphenolic compound. The release profiles displayed pH dependence, exhibiting notably faster release at pH 5.2 compared to pH 7.4. The gradual release of RES over time demonstrated an initial time lag of approximately 4 h, being well described by the Weibull model. In vitro cytotoxicity studies were conducted on human osteosarcoma cells (MG-63), revealing a concentration-dependent decrease in cell viability for RES-loaded samples (for concentrations >50 µg mL-1).

4.
Nat Genet ; 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38637617

RESUMO

Post-traumatic stress disorder (PTSD) genetics are characterized by lower discoverability than most other psychiatric disorders. The contribution to biological understanding from previous genetic studies has thus been limited. We performed a multi-ancestry meta-analysis of genome-wide association studies across 1,222,882 individuals of European ancestry (137,136 cases) and 58,051 admixed individuals with African and Native American ancestry (13,624 cases). We identified 95 genome-wide significant loci (80 new). Convergent multi-omic approaches identified 43 potential causal genes, broadly classified as neurotransmitter and ion channel synaptic modulators (for example, GRIA1, GRM8 and CACNA1E), developmental, axon guidance and transcription factors (for example, FOXP2, EFNA5 and DCC), synaptic structure and function genes (for example, PCLO, NCAM1 and PDE4B) and endocrine or immune regulators (for example, ESR1, TRAF3 and TANK). Additional top genes influence stress, immune, fear and threat-related processes, previously hypothesized to underlie PTSD neurobiology. These findings strengthen our understanding of neurobiological systems relevant to PTSD pathophysiology, while also opening new areas for investigation.

6.
Antibiotics (Basel) ; 13(3)2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38534631

RESUMO

The pioneering medical application of peptides as therapeutics began approximately a century ago; however, they remain clinically relevant candidates garnering more attention on the drug development agenda [...].

7.
Adv Med Sci ; 69(1): 153-159, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38490331

RESUMO

PURPOSE: New-onset diabetes after transplantation (NODAT) is a frequent metabolic complication associated with podocyte damage and renal allograft dysfunction. Thus, Wilm's tumor-1 (WT-1) protein, as a podocyte marker, holds promise as an option to evaluate renal allograft dysfunction in NODAT. Therefore, the study aimed to investigate urinary WT-1 levels in NODAT patients during the first year after kidney transplantation (KTx). MATERIALS AND METHODS: KTx patients were categorized into non-NODAT and NODAT groups. Fasting blood glucose, glycated hemoglobin (HbA1c), urinary albumin/creatinine ratio (ACR), serum creatinine, estimated glomerular filtration rate (eGFR), and urinary WT-1 were measured at 3, 6, 9, and 12-months post-KTx. RESULTS: The NODAT group manifested elevated levels of blood glucose and HbA1c during the first year post-KTx. Also, exhibited elevations in ACR and serum creatinine levels at 6, 9, and 12-months post-KTx when compared to non-NODAT group. Conversely, eGFR values in the NODAT group demonstrated significant declines at 3, 6, and 9-months post-KTx relative to non-NODAT. Furthermore, NODAT group exhibited a median annual eGFR of 47 â€‹mL/min/1.73 â€‹m2. Urinary WT-1 levels at 3, 6, 9, and 12-months post-KTx were significantly higher in the NODAT group compared to non-NODAT. Additionally, noteworthy positive correlations were identified between urinary WT-1 and HbA1c levels, along with significant negative correlations between urinary WT-1 and eGFR at the 3, 6, 9, and 12-months post-KTx. CONCLUSION: The increased urinary WT-1 levels from 3-months post-KTx in NODAT patients may indicate the first sign of podocyte injury, predicting a renal allograft dysfunction in these patients.

8.
Nutrients ; 16(6)2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38542797

RESUMO

This paper presents baseline results from the NutriEcoMuscle study, a multicenter observational study conducted in Spain which focused on changes in nutritional status, body composition, and functionality in post-intensive care unit (ICU) COVID-19 patients following a nutritional intervention. Assessments at hospital discharge included Subjective Global Assessment (SGA), Global Leadership Initiative on Malnutrition (GLIM) criteria, the Barthel index, handgrip strength (HGS) and the Timed Up-and-Go test, bioelectrical impedance analysis (BIA), and nutritional ultrasound (US). The study involved 96 patients (71.9% male, mean age 58.8 years, mean BMI 28.8 kg/m2, 36.5% obese). All patients were malnourished at discharge according to GLIM and SGA. Functional status declined from admission up to hospital discharge. A total of 33.3% of patients had a low fat-free mass index (FFMI) and 29.5% had a low phase angle (PhA). Myosteatosis was observed in 83.7% of the population. There was a positive correlation between rectus femoris cross-sectional area, PhA, FFMI, and HGS. In conclusion, post-critically ill COVID-19 patients commonly suffer from malnutrition and reduced muscle mass, causing a loss of independence at hospital discharge. BIA and US could be valuable tools for assessing body composition in these patients. The NutriEcoMuscle study highlights the need for a thorough nutritional and morphofunctional status assessment of post-ICU patients.


Assuntos
COVID-19 , Desnutrição , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Avaliação Nutricional , Alta do Paciente , Força da Mão , COVID-19/complicações , Estado Nutricional , Desnutrição/epidemiologia , Unidades de Terapia Intensiva , Hospitais
9.
Nat Methods ; 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38532015

RESUMO

Cell segmentation is a critical step for quantitative single-cell analysis in microscopy images. Existing cell segmentation methods are often tailored to specific modalities or require manual interventions to specify hyper-parameters in different experimental settings. Here, we present a multimodality cell segmentation benchmark, comprising more than 1,500 labeled images derived from more than 50 diverse biological experiments. The top participants developed a Transformer-based deep-learning algorithm that not only exceeds existing methods but can also be applied to diverse microscopy images across imaging platforms and tissue types without manual parameter adjustments. This benchmark and the improved algorithm offer promising avenues for more accurate and versatile cell analysis in microscopy imaging.

11.
Front Nutr ; 11: 1335052, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38463940

RESUMO

Introduction: Bioelectrical impedance analysis (BIA) serves as a method to estimate body composition. Parameters such as phase angle (PA), standardized phase angle (SPA), body mass cell (BCM), BCM index (BCMI), and fat-free mass (FFM) might significantly impact the prognosis of head and neck cancer (HNC) patients. The present study aimed to investigate whether bioelectrical parameters can be used to predict survival in the HNC population and establish the optimal cutoff points for predictive accuracy. Methods: A multicenter observational study was performed across 12 tertiary hospitals in Andalusia (a region from the south of Spain). A total of 494 patients diagnosed with HNC between 2020 and 2022 at different stages were included in this study, with a minimum follow-up period of 12 months. The BIA assessment was carried out during the first 2 weeks of radical radiotherapy treatment with chemotherapy or other systemic treatments. A multivariate logistic regression analysis of overall survival, complications, hospital admission, and palliative care and its relationship with BIA nutritional assessment was performed. Results: Significant prognostic factors identified in the multivariable analysis encompassed phase angle (PA), standardized phase angle (SPA), body cell mass (BCM), and BCM index (BCMI). Lower PA and BCM values were significantly associated with adverse clinical outcomes. A BCM threshold above 17 kg/m2 was the most significant predictor for predicting survival within the overall HNC population. The PA values of <5.1° in male and <4.8° in female patients showed the best predictive potential for mortality. Increased PA (as a continuous variable) demonstrated a significantly reduced risk for mortality (OR, 0.64; 95% CI, 0.43-0.94; p < 0.05) and a decreased likelihood of hospital admission (OR, 0.75; 95% CI, 0.52-1.07; p < 0.05). Higher BCM correlated with a lower risk of mortality (OR, 0.88; 95% CI, 0.80-0.96; p < 0.01) and a diminished probability of hospital admission (OR, 0.91; 95% CI, 0.83-0.99; p < 0.05). Conclusion: BIA is a crucial tool in the nutritional assessment of HNC patients. BCM and PA are the main bioelectrical parameters used to predict clinical outcomes in this population. Future studies are needed to validate BIA variables in a large cohort to ensure whether early intensification of nutritional treatment would improve survival.

12.
J Vasc Surg Cases Innov Tech ; 10(3): 101432, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38510090

RESUMO

Venous in-stent restenosis is not completely understood, and the currently available treatment is usually unsatisfactory. We describe the cases of two patients treated with the RevCore thrombectomy system (Inari Medical), designed for venous in-stent thrombosis. Case 1 involves a 62-year-old woman with post-thrombotic syndrome from iliac vein stent placement 15 years earlier. Case 2 describes a 30-year-old woman with post-thrombotic syndrome from recurrent iliac vein stent occlusion, despite therapeutic anticoagulation. Both patients had previous recanalization attempts at outside facilities that were unsuccessful. The RevCore system was safe and feasible in these initial cases, and more studies are warranted.

13.
Comput Biol Med ; 171: 108216, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38442555

RESUMO

Despite being one of the most prevalent forms of cancer, prostate cancer (PCa) shows a significantly high survival rate, provided there is timely detection and treatment. Computational methods can help make this detection process considerably faster and more robust. However, some modern machine-learning approaches require accurate segmentation of the prostate gland and the index lesion. Since performing manual segmentations is a very time-consuming task, and highly prone to inter-observer variability, there is a need to develop robust semi-automatic segmentation models. In this work, we leverage the large and highly diverse ProstateNet dataset, which includes 638 whole gland and 461 lesion segmentation masks, from 3 different scanner manufacturers provided by 14 institutions, in addition to other 3 independent public datasets, to train accurate and robust segmentation models for the whole prostate gland, zones and lesions. We show that models trained on large amounts of diverse data are better at generalizing to data from other institutions and obtained with other manufacturers, outperforming models trained on single-institution single-manufacturer datasets in all segmentation tasks. Furthermore, we show that lesion segmentation models trained on ProstateNet can be reliably used as lesion detection models.


Assuntos
Próstata , Neoplasias da Próstata , Masculino , Humanos , Próstata/diagnóstico por imagem , Imageamento Tridimensional/métodos , Estudos Retrospectivos , Algoritmos , Neoplasias da Próstata/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos
14.
Sensors (Basel) ; 24(5)2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38475198

RESUMO

An optical fiber pH sensor based on a long-period fiber grating (LPFG) is reported. Two oppositely charged polymers, polyethylenimine (PEI) and polyacrylic acid (PAA), were alternately deposited on the sensing structure through a layer-by-layer (LbL) electrostatic self-assembly technique. Since the polymers are pH sensitive, their refractive index (RI) varies when the pH of the solution changes due to swelling/deswelling phenomena. The fabricated multilayer coating retained a similar property, enabling its use in pH-sensing applications. The pH of the PAA dipping solution was tuned so that a coated LPFG achieved a pH sensitivity of (6.3 ± 0.2) nm/pH in the 5.92-9.23 pH range. Only two bilayers of PEI/PAA were used as an overlay, which reduces the fabrication time and increases the reproducibility of the sensor, and its reversibility and repeatability were demonstrated by tracking the resonance band position throughout multiple cycles between different pH solutions. With simulation work and experimental results from a low-finesse Fabry-Perot (FP) cavity on a fiber tip, the coating properties were estimated. When saturated at low pH, it has a thickness of 200 nm and 1.53 ± 0.01 RI, expanding up to 310 nm with a 1.35 ± 0.01 RI at higher pH values, mostly due to the structural changes in the PAA.

15.
J Nat Prod ; 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38449376

RESUMO

Snake venoms contain various bradykinin-potentiating peptides (BPPs). First studied for their vasorelaxant properties due to angiotensin converting enzyme (ACE) inhibition, these molecules present a range of binding partners, among them the argininosuccinate synthase (AsS) enzyme. This has renewed interest in their characterization from biological sources and the evaluation of their pharmacological activities. In the present work, the low molecular weight fraction of Bothrops moojeni venom was obtained and BPPs were characterized by mass spectrometry. Eleven BPPs or related peptides were sequenced, and one of them, BPP-Bm01, was new. Interestingly, some oxidized BPPs were detected. The three most abundant peptides were BPP-Bm01, BPP-Bax12, and BPP-13a, and their putative interactions with the AsS enzyme were investigated in silico. A binding cavity for these molecules was predicted, and docking studies allowed their ranking. Three peptides were synthesized and submitted to vasorelaxation assays using rat aortic rings. While all BPPs were active, BPP-Bm01 showed the highest potency in this assay. This work adds further diversity to BPPs from snake venoms and suggests, for the first time, a putative binding pocket for these molecules in the AsS enzyme. This can guide the design of new and more potent AsS activators.

16.
PLoS One ; 19(3): e0299041, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38437222

RESUMO

INTRODUCTION: Over the past decade, there has been a heightened interest in evaluating self-efficacy among patients with coronary artery disease (CAD). A significant number of instruments have been developed and validated, yet the need remains to assess the quality of their studies and their properties. OBJECTIVES: To evaluate the measurement properties and link the content extracted from self-efficacy instrument items for individuals with CAD to the International Classification of Functioning, Disability, and Health (ICF). METHODOLOGY: The study was conducted following the Cochrane systematic review guidelines and COnsensus norms for Selection of health Measuring INstruments (COSMIN), registered under CRD42021262613. The search was carried out on MEDLINE (Ovid), Web of Science, EMBASE, and PsycINFO, including studies involving the development and validation of self-efficacy instruments for individuals with CAD, without language or date restrictions. Data extraction was performed in May 2022 and updated in January 2023 and all the steps of this review were carried out by two different collaborators and reviewed by a third when there were divergences. Modified Grading of Recommendations, Assessment, Development and Evaluation (GRADE) recommended by COSMIN was used to determine the quality of evidence as high, moderate, low, or very low. Instrument categorization was carried out per COSMIN recommendations, according to the construct of interest and study population into three categories (A, B, or C). RESULTS: A total of 21 studies from 12 instruments were identified. The best-rated instruments received a recommendation of B, which means, additional validation studies are needed. Barnason Efficacy Expectation Scale (BEES) showed high-quality evidence for structural, construct, criterion, and internal consistency validity; Cardiac Self-Efficacy Scale (CSES) demonstrated high quality for content, structural, cross-cultural validity, and internal consistency; Self-efficacy for Appropriate Medication Use (SEAMS) achieved a high level for structural, criterion, and internal consistency validity; Cardiovascular Management Self-Efficacy Scale exhibited high-level validity for structural, criterion, construct, and internal consistency. The CSES showed content linkage with all domains of the ICF, as well as the highest number of linkages with the categories. CONCLUSIONS: Instruments with a B-level recommendation hold potential for use. More studies assessing measurement properties are needed to reinforce or improve these recommendations. The CSES stands out as the most comprehensive instrument concerning the ICF.


Assuntos
Doença da Artéria Coronariana , Humanos , Consenso , Abordagem GRADE , Coração , Autoeficácia
17.
Psychiatry Res ; 334: 115801, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38402741

RESUMO

The aim of this article is to study mental health conditions among survivors of severe physical intimate partner violence (IPV) and their utilisation of mental health services. This study is an integrated part of the World Mental Health Survey Initiative-Portugal, for which data was collected from a nationally representative adult sample using well-validated scales. Logistic regression models were used in the analysis. The most common statistically significant mental health conditions among IPV survivors were suicide ideation, PTSD, major depressive episode, and generalised anxiety disorder. More than one in three survivors developed PTSD. Suicide ideation was likely to occur after first experiencing IPV. Almost a half of survivors received specialised mental health treatment; in most cases, delivered by a psychiatrist. Over 60 % addressed their mental health issues consulting general physicians or other healthcare professionals. Those who experienced family violence in childhood had greater odds of also experiencing IPV; survivors of IPV with this experience were more likely to receive mental health treatment. The need to promote greater awareness and competencies of not only mental health professionals but also of general physicians and other healthcare professionals to provide support more effectively to survivors of any type of IPV deserves to be emphasised.


Assuntos
Transtorno Depressivo Maior , Violência por Parceiro Íntimo , Serviços de Saúde Mental , Adulto , Humanos , Saúde Mental , Portugal/epidemiologia , Violência por Parceiro Íntimo/psicologia , Inquéritos Epidemiológicos , Sobreviventes/psicologia , Organização Mundial da Saúde
18.
Nutrients ; 16(3)2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38337671

RESUMO

Head and neck cancer (HNC) is a prevalent and aggressive form of cancer with high mortality rates and significant implications for nutritional status. Accurate assessment of malnutrition in patients with HNC is crucial for optimizing treatment outcomes and improving survival rates. This study aimed to evaluate the use of ultrasound techniques for predicting nutritional status, malnutrition, and cancer outcomes in patients with HNC. A total of 494 patients with HNC were included in this cross-sectional observational study. Various tools and body composition measurements, including muscle mass and adipose tissue ultrasound evaluations, were implemented. Using regression models, we mainly found that high levels of RF-CSA (rectus femoris cross-sectional area) were associated with a decreased risk of malnutrition (as defined with GLIM criteria (OR = 0.81, 95% CI: 0.68-0.98); as defined with PG-SGA (OR = 0.78, 95% CI: 0.62-0.98)) and sarcopenia (OR = 0.64, 95% CI: 0.49-0.82) after being adjusted for age, sex, and BMI. To predict the importance of muscle mass ultrasound variables on the risk of mortality, a nomogram, a random forest, and decision tree models were conducted. RF-CSA was the most important variable under the random forest model. The obtained C-index for the nomogram was 0.704, and the Brier score was 16.8. With an RF-CSA < 2.7 (AUC of 0.653 (0.59-0.77)) as a split, the decision tree model classified up to 68% of patients as possessing a high probability of survival. According to the cut-off value of 2.7 cm2, patients with a low RF-CSA value lower than 2.7 cm2 had worse survival rates (p < 0.001). The findings of this study highlight the importance of implementing ultrasound tools, for accurate diagnoses and monitoring of malnutrition in patients with HNC. Adipose tissue ultrasound measurements were only weakly associated with malnutrition and not with sarcopenia, indicating that muscle mass is a more important indicator of overall health and nutritional status. These results have the potential to improve survival rates and quality of life by enabling early intervention and personalized nutritional management.


Assuntos
Neoplasias de Cabeça e Pescoço , Desnutrição , Sarcopenia , Humanos , Estudos Prospectivos , Qualidade de Vida , Sarcopenia/diagnóstico por imagem , Sarcopenia/etiologia , Prognóstico , Neoplasias de Cabeça e Pescoço/complicações , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Desnutrição/etiologia , Estado Nutricional , Músculo Quadríceps , Avaliação Nutricional
19.
BMJ Open Respir Res ; 11(1)2024 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-38387997

RESUMO

BACKGROUND: Respiratory diseases (RDs) cause millions of hospitalisations and deaths worldwide, resulting in economic and social impacts. Strategies for health promotion and disease prevention based on the epidemiological profile of the population may reduce hospital costs. AIM: To characterise hospitalisations and deaths due to RDs in Brazilian adults above 20 years old between 2008 and 2021. METHODS: This ecological study used secondary data of hospitalisations and deaths due to RDs from the Hospital Information System of the Brazilian Unified Health System between 2008 and 2021. Data were grouped according to region, age group and sex. The period was divided into first (2008-2011), second (2012-2015) and third (2016-2019) quadrennia and one biennium (2020-2021), and all data were analysed using the GraphPad Prism; statistical significance was set at p<0.05. RESULTS: A total of 9 502 378 hospitalisations due to RDs were registered between 2008 and 2021. The south and southeast regions presented the highest hospitalisation and fatality rate, respectively, in the age group ≥80 years with no significant differences between sexes. Also, RDs caused 1 170 504 deaths, with a national fatality rate of 12.32%. CONCLUSION: RDs affected the Brazilian population and impaired the health system, especially the hospital environment. The south/southeast regions were the most affected, and the ageing process contributed to the increased incidence of RDs.


Assuntos
Transtornos Respiratórios , Doenças Respiratórias , Adulto , Humanos , Idoso de 80 Anos ou mais , Adulto Jovem , Brasil/epidemiologia , Estudos Longitudinais , Hospitalização , Doenças Respiratórias/epidemiologia
20.
Sci Rep ; 14(1): 3184, 2024 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-38326450

RESUMO

Local tissue damage following snakebite envenoming remains a poorly researched area. To develop better strategies to treat snakebites, it is critical to understand the mechanisms through which venom toxins induce envenomation effects including local tissue damage. Here, we demonstrate how the venoms of two medically important Indian snakes (Russell's viper and cobra) affect human skeletal muscle using a cultured human myoblast cell line. The data suggest that both venoms affect the viability of myoblasts. Russell's viper venom reduced the total number of cells, their migration, and the area of focal adhesions. It also suppressed myogenic differentiation and induced muscle atrophy. While cobra venom decreased the viability, it did not largely affect cell migration and focal adhesions. Cobra venom affected the formation of myotubes and induced atrophy. Cobra venom-induced atrophy could not be reversed by small molecule inhibitors such as varespladib (a phospholipase A2 inhibitor) and prinomastat (a metalloprotease inhibitor), and soluble activin type IIb receptor (a molecule used to promote regeneration of skeletal muscle), although the antivenom (raised against the Indian 'Big Four' snakes) has attenuated the effects. However, all these molecules rescued the myotubes from Russell's viper venom-induced atrophy. This study demonstrates key steps in the muscle regeneration process that are affected by both Indian Russell's viper and cobra venoms and offers insights into the potential causes of clinical features displayed in envenomed victims. Further research is required to investigate the molecular mechanisms of venom-induced myotoxicity under in vivo settings and develop better therapies for snakebite-induced muscle damage.


Assuntos
Víbora de Russell , Mordeduras de Serpentes , Humanos , Animais , Naja naja , Mordeduras de Serpentes/tratamento farmacológico , Venenos de Víboras/toxicidade , Elapidae , Venenos Elapídicos/farmacologia , Venenos Elapídicos/uso terapêutico , Mioblastos , Atrofia
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