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1.
BMJ Case Rep ; 17(4)2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38569730

RESUMO

An outborn male term neonate presented with a complaint of respiratory distress since birth on day 9 of life. On examination, baby was having tachypnoea, tachycardia and hepatomegaly. The baby was delivered at term gestation and cried immediately after birth. The chest X-ray showed cardiomegaly. The abdomen ultrasound showed a complex cystic vascular lesion suggestive of hepatic haemangioma. The echocardiography showed an atrial septal defect. The baby was initially treated conservatively along with specific treatment (steroids and propranolol) for haemangioma for 6 weeks. However, the symptoms persisted and there was non-resolution, therefore, particle embolisation of the right hepatic artery was performed. Subsequently, it resulted in complete resolution of the lesion.


Assuntos
Hemangioma , Neoplasias Hepáticas , Recém-Nascido , Lactente , Humanos , Masculino , Hemangioma/diagnóstico por imagem , Hemangioma/terapia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/terapia , Propranolol/uso terapêutico , Artéria Hepática , Ultrassonografia
2.
J Alzheimers Dis Rep ; 8(1): 371-385, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38549638

RESUMO

Background: Amyloid-ß plaques (Aß) are associated with Alzheimer's disease (AD). Pooled assessment of amyloid reduction in transgenic AD mice is critical for expediting anti-amyloid AD therapeutic research. Objective: The mean threshold of Aß reduction necessary to achieve cognitive improvement was measured via pooled assessment (n = 594 mice) of Morris water maze (MWM) escape latency of transgenic AD mice treated with substances intended to reduce Aß via reduction of beta-secretase cleaving enzyme (BACE). Methods: Machine learning and statistical methods identified necessary amyloid reduction levels using mouse data (e.g., APP/PS1, LPS, Tg2576, 3xTg-AD, control, wild type, treated, untreated) curated from 22 published studies. Results: K-means clustering identified 4 clusters that primarily corresponded with level of Aß: untreated transgenic AD control mice, wild type mice, and two clusters of transgenic AD mice treated with BACE inhibitors that had either an average 25% "medium reduction" of Aß or 50% "high reduction" of Aß compared to untreated control. A 25% Aß reduction achieved a 28% cognitive improvement, and a 50% Aß reduction resulted in a significant 32% improvement compared to untreated transgenic mice (p < 0.05). Comparatively, wild type mice had a mean 41% MWM latency improvement over untreated transgenic mice (p < 0.05). BACE reduction had a lesser impact on the ratio of Aß42 to Aß40. Supervised learning with an 80% -20% train-test split confirmed Aß reduction was a key feature for predicting MWM escape latency (R2 = 0.8 to 0.95). Conclusions: Results suggest a 25% reduction in Aß as a meaningful treatment threshold for improving transgenic AD mouse cognition.

3.
J Biomech Eng ; 146(5)2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38376449

RESUMO

The COVID-19 pandemic necessitated mainstream adoption of online and remote learning approaches, which were highly advantageous yet challenging in many ways. The online modality, while teaching biomedical engineering-related topics in the areas of biomechanics, mechanobiology, and biomedical sciences, further added to the complexity faced by the faculty and students. Both the benefits and the challenges have not been explored systematically by juxtaposing experiences and reflections of both the faculty and students. Motivated by this need, we designed and conducted a systematic survey named BIORES-21, targeted toward the broader bio-engineering community. Survey responses and our inferences from survey findings cumulatively offer insight into the role of employed teaching/learning technology and challenges associated with student engagement. Survey data also provided insights on what worked and what did not, potential avenues to address some underlying challenges, and key beneficial aspects such as integration of technology and their role in improving remote teaching/learning experiences. Overall, the data presented summarize the key benefits and challenges of online learning that emerged from the experiences during the pandemic, which is valuable for the continuation of online learning techniques as in-person education operations resumed broadly across institutions, and some form of online learning seems likely to sustain and grow in the near future.


Assuntos
Educação a Distância , Humanos , Fenômenos Biomecânicos , Pandemias , Biofísica , Aprendizagem
4.
J Biomech Eng ; 146(4)2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38270930

RESUMO

The human body represents a collection of interacting systems that range in scale from nanometers to meters. Investigations from a systems perspective focus on how the parts work together to enact changes across spatial scales, and further our understanding of how systems function and fail. Here, we highlight systems approaches presented at the 2022 Summer Biomechanics, Bio-engineering, and Biotransport Conference in the areas of solid mechanics; fluid mechanics; tissue and cellular engineering; biotransport; and design, dynamics, and rehabilitation; and biomechanics education. Systems approaches are yielding new insights into human biology by leveraging state-of-the-art tools, which could ultimately lead to more informed design of therapies and medical devices for preventing and treating disease as well as rehabilitating patients using strategies that are uniquely optimized for each patient. Educational approaches can also be designed to foster a foundation of systems-level thinking.


Assuntos
Bioengenharia , Análise de Sistemas , Humanos , Fenômenos Biomecânicos , Biofísica
5.
J Vis Exp ; (203)2024 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-38284518

RESUMO

Peripheral nerves undergo physiological and non-physiological stretch during development, normal joint movement, injury, and more recently while undergoing surgical repair. Understanding the biomechanical response of peripheral nerves to stretch is critical to the understanding of their response to different loading conditions and thus, to optimizing treatment strategies and surgical interventions. This protocol describes in detail the calibration process of the stereo-imaging camera system via direct linear transformation and the tracking of the three-dimensional in-situ tissue displacement of peripheral nerves during stretch, obtained from three-dimensional coordinates of the video files captured by the calibrated stereo-imaging camera system. From the obtained three-dimensional coordinates, the nerve length, change in the nerve length, and percent strain with respect to time can be calculated for a stretched peripheral nerve. Using a stereo-imaging camera system provides a non-invasive method for capturing three-dimensional displacements of peripheral nerves when stretched. Direct linear transformation enables three-dimensional reconstructions of peripheral nerve length during stretch to measure strain. Currently, no methodology exists to study the in-situ strain of stretched peripheral nerves using a stereo-imaging camera system calibrated via direct linear transformation. Capturing the in-situ strain of peripheral nerves when stretched can not only aid clinicians in understanding underlying injury mechanisms of nerve damage when overstretched but also help optimize treatment strategies that rely on stretch-induced interventions. The methodology described in the paper has the potential to enhance our understanding of peripheral nerve biomechanics in response to stretch to improve patient outcomes in the field of nerve injury management and rehabilitation.


Assuntos
Traumatismos dos Nervos Periféricos , Nervos Periféricos , Humanos , Nervos Periféricos/fisiologia , Fenômenos Biomecânicos , Resistência à Tração , Movimento
6.
Discov Med ; 36(180): 22-47, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38273744

RESUMO

Idiopathic pulmonary fibrosis is a progressive and incurable lung disease characterized by collagen deposition, alveolar inflammation, fibroblast proliferation, and the destruction of lung tissue structures. It is a rare yet severe condition with a high mortality rate, typically leading to death within 3-5 years of diagnosis. The clinical presentation of idiopathic pulmonary fibrosis (IPF) involves a gradual and substantial loss of lung function, ultimately resulting in respiratory failure. Despite more than half a century of intensive research, the origin of IPF remains a mystery. Despite its unknown etiology, several genetic and non-genetic factors have been linked to IPF. Recent significant advancements have been made in the field of IPF diagnosis and treatment. Two oral small-molecule drugs, pirfenidone and nintedanib, have recently gained approval for the treatment of IPF. Pirfenidone exhibits antifibrotic, antioxidant, and anti-inflammatory properties, while nintedanib is a tyrosine kinase inhibitor with selectivity for vascular endothelial growth factor (VEGF) receptors, prostaglandin F (PGF) receptors, and fibroblast growth factor (FGF) receptors. Both of these compounds are capable of slowing down the progression of the disease with an acceptable safety profile. This review provides a brief introduction, historical background, epidemiological insights, and an exploration of various environmental risk factors that may influence the lung microenvironment and contribute to the advancement of IPF. The review also delves into the diagnosis, signaling pathways, and ongoing clinical trials worldwide. A thorough review of the literature was conducted using PubMed and Google Scholar to gather information on various aspects of IPF. Numerous potential drugs are currently under investigation in clinical trials, and the completion of this process is crucial to the ultimate goal of finding a cure for IPF patients. The investigation of the role of genes, surfactant proteins, infectious agents, biomarkers, and epigenetic changes holds the promise of offering earlier and more accurate understanding and diagnosis of IPF. This information could be instrumental in the development of new therapeutic approaches for treating IPF and is expected to be of great interest to researchers.


Assuntos
Fibrose Pulmonar Idiopática , Fator A de Crescimento do Endotélio Vascular , Humanos , Fibrose Pulmonar Idiopática/diagnóstico , Fibrose Pulmonar Idiopática/tratamento farmacológico , Pulmão/metabolismo , Inflamação/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Piridonas/uso terapêutico , Piridonas/farmacologia
7.
J Biomech Eng ; 146(2)2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38116838

RESUMO

The purpose of this computational study was to investigate the effects of neonate-focused clinical delivery maneuvers on brachial plexus (BP) during shoulder dystocia. During shoulder dystocia, the anterior shoulder of the neonate is obstructed behind the symphysis pubis of the maternal pelvis, postdelivery of the neonate's head. This is managed by a series of clinical delivery maneuvers. The goal of this study was to simulate these delivery maneuvers and study their effects on neonatal BP strain. Using madymo models of a maternal pelvis and a 90th-percentile neonate, various delivery maneuvers and positions were simulated including the lithotomy position alone of the maternal pelvis, delivery with the application of various suprapubic pressures (SPPs), neonate in an oblique position, and during posterior arm delivery maneuver. The resulting BP strain (%) along with the required maternal delivery force was reported in these independently simulated scenarios. The lithotomy position alone served as the baseline. Each of the successive maneuvers reported a decrease in the required delivery force and resulting neonatal BP strain. As the applied SPP force increased (three scenarios simulated), the required maternal delivery force and neonatal BP strain decreased. A further decrease in both delivery force and neonatal BP strain was observed in the oblique position, with the lowest delivery force and neonatal BP strain reported during the posterior arm delivery maneuver. Data obtained from the improved computational models in this study enhance our understanding of the effects of clinical maneuvers on neonatal BP strain during complicated birthing scenarios such as shoulder dystocia.


Assuntos
Plexo Braquial , Distocia , Distocia do Ombro , Gravidez , Recém-Nascido , Feminino , Humanos , Parto Obstétrico/efeitos adversos , Parto Obstétrico/métodos , Distocia/etiologia
8.
BMJ Case Rep ; 16(12)2023 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-38129091

RESUMO

Hydrometrocolpos is a rare finding in newborns. It can be an isolated finding or may be associated with syndromes. Antenatal diagnosis is possible. It is due to the accumulation of secretion in the uterus, distending it and resulting in abdominal swelling. In case of suspected syndromes, an attempt should be made to look for other organ involvement and genetic diagnosis. We here report a term neonate with hydrometrocolpos, which was antenatally diagnosed and was managed conservatively.


Assuntos
Hidrocolpos , Anormalidades Urogenitais , Doenças Uterinas , Gravidez , Recém-Nascido , Humanos , Feminino , Hidrocolpos/diagnóstico por imagem , Diagnóstico Pré-Natal , Doenças Uterinas/diagnóstico , Útero
9.
Biosensors (Basel) ; 13(10)2023 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-37887137

RESUMO

Monitoring and controlling the microclimate at the skin-socket interface of limb prostheses is an important, yet unresolved, clinical problem. Phase-change materials (PCMs) represent a promising biosensor technology that holds the potential to both detect and alter (i.e., stabilize) changes in the temperature of a hybrid biological/mechanical system, such as a prosthesis. The biologically inspired sensor capabilities of PCMs can enhance the internal socket conditions and offer improved comfort and suspension while minimizing skin injuries for prosthesis users. This study investigated how prosthetic liners equipped with PCM biosensors affected the long-term outcomes for prosthesis users. In this double-blinded longitudinal crossover study, a cohort of transtibial prosthesis users wore regular conventional liners for six months and PCM liners for another six months. Prosthesis utilization, physical performance, and gait symmetry were studied using Modus StepWatch, the 2-minute walk test, and the TekScan F-Scan gait test, respectively. Measured parameters from these various tests, acquired at multiple timepoints during the study, were compared pairwise between the two liners per individual. While the obtained quantitative data trends, such as the gait symmetry, favored the PCM liners, no statistically significant differences were found between the PCM and conventional gel liners in any of the study parameters.


Assuntos
Membros Artificiais , Humanos , Desenho de Prótese , Estudos Cross-Over , Marcha
10.
Enzyme Microb Technol ; 171: 110304, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37639935

RESUMO

Depleting fossil fuels and net carbon emissions associated with their burning have driven the need to find alternative energy sources. Biofuels are near-perfect candidates for alternative energy sources as they are renewable and account for no net CO2 emissions. However, biofuel production must overcome various challenges to compete with conventional fuels. Conventional methods for bioconversion of biomass to biofuel include chemical, thermochemical, and biological processes. Substrate selection and processing, low yield, and total cost of production are some of the main issues associated with biofuel generation. Recently, the uses of nanotechnology and nanoparticles have been explored to improve the biofuel production processes because of their high adsorption, high reactivity, and catalytic properties. The role of these nanoscale particles and nanocatalysts in biomass conversion and their effect on biofuel production processes and yield are discussed in the present article. The applicability of nanotechnology in production processes of biobutanol, bioethanol, biodiesel, biohydrogen, and biogas under biorefinery approach are presented. Different types of nanoparticles, and their function in the bioprocess, such as electron transfer, pretreatment, hydrolysis, microalgae cultivation, lipid extraction, dark and photo fermentation, immobilization, and suppression of inhibitory compounds, are also highlighted. Finally, the current and potential applications of nanotechnology in biorefineries are also discussed.

11.
PLoS One ; 18(8): e0290718, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37647327

RESUMO

Neonatal brachial plexus palsy (NBPP) results from over-stretching of the neonatal brachial plexus during complicated birthing scenarios. The lack of information on the biomechanical response of the neonatal brachial plexus complex when subjected to stretch limits our understanding of the NBPP injury mechanism. This study aims to fill that critical gap by using a neonatal piglet animal model and providing the in vivo biomechanical properties of the neonatal brachial plexus complex when subjected to stretch. Forty-seven brachial plexus levels (identified by the four brachial plexus terminal nerve branches namely musculocutaneous, median, ulnar, and radial), obtained from 16 neonatal Yorkshire piglets (3-5 days old), were subjected to stretch-induced failure. The average maximum load and corresponding strain were reported to be 16.6 ± 1.3 N and 36.1 ± 1.6%, respectively. Maximum loads reported at the musculocutaneous level were significantly lower than the median and radial levels. No differences in strains at failure were reported at all four tested levels. Proximal or distal failure locations were reported in 83% of the tests with 17% mid-length ruptures that were primarily reported at the bifurcation of the median and ulnar brachial plexus levels. Histological studies reported an overall loss of wavy pattern of the nerve fibers, an increase in nerve spacing, fiber disruptions, and blood vessel ruptures in the stretched tissue. This in vivo piglet animal study offers insight into the NBPP mechanism by reporting biomechanical, injury location, and structural damage responses in neonatal brachial plexus when subjected to stretch.


Assuntos
Nervo Mediano , Fibras Nervosas , Animais , Suínos , Gravidez , Feminino , Modelos Animais , Parto , Projetos de Pesquisa
12.
Cent Nerv Syst Agents Med Chem ; 23(1): 13-31, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37394979

RESUMO

OBJECTIVES: Elaeocarpus ganitrus, a member of the Eleocarpaceae family, is valued in Hinduism and Ayurveda, and is frequently used as a remedy for a variety of illnesses. The plant is reputed to treat a number of stomach issues. The purpose of the study was to produce high-quality scientific data regarding gastroprotective behavior, docking experiments with cholinergic receptors, and HPTLC (with lupeol and ursolic acid). To develop the mechanism of herbal extracts, in vitro anticholinergic and antihistaminic activities were evaluated. Different leaf extracts were treated with various reagents to determine the presence of various metabolites. An examination of the histopathology was conducted to determine the full impact of the extract. METHODS: Methanolic extract was chosen for HPTLC investigations after extraction with various solvents. A mobile phase of toluene, ethylacetate, and formic acid (8:2:0.1) was chosen. Molecular docking was utilized to examine how ursolic acid and lupeol are bound to cholinergic receptors (M3). Different extracts (aqueous and ethanolic) were tested for their ability to provide gastroprotection in Wistar rats at different doses (200 and 400 mg/kg). RESULTS: Phytochemical analysis of different extracts showed the presence of different primary and secondary metabolites. HPTLC data showed the presence of both standards. Docking studies exhibited very good interactions with the M3 receptor. Pharmacological studies revealed that extract-treated groups significantly reduced the ulcer index in all of the models mentioned above. The histopathological analysis clearly supports the biochemical studies, which were conducted utilizing various doses and found to be effective in a dose-dependent manner. The in vitro analysis proved that the abovementioned extracts may act as antagonists of acetylcholine and histamine. CONCLUSION: The data obtained would be valuable for the production of the monograph of the plant and conducting concept-related clinical studies in the future. More investigation is required since the gathered scientific data may lead to new research opportunities.


Assuntos
Antiulcerosos , Elaeocarpaceae , Úlcera Gástrica , Ratos , Animais , Ratos Wistar , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Extratos Vegetais/química , Simulação de Acoplamento Molecular , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/patologia , Antiulcerosos/farmacologia , Antiulcerosos/uso terapêutico , Antiulcerosos/química
13.
Bioengineered ; 14(1): 81-112, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37401849

RESUMO

Bioethanol is an appropriate alternate energy option due to its renewable, nontoxic, environmentally friendly, and carbon-neutral nature. Depending upon various feedstocks, bioethanol is classified in different various generations. First-generation ethanol created a food vs fuel problem, which was overcome by second-generation, third-generation and fourth-generation ethanol. The considerable availability of lignocellulosic biomass makes it a suitable feedstock, however, its recalcitrant nature is the main hurdle in converting it to bioethanol. The present study gives a comprehensive assessment of global biofuel policies and the current status of ethanol production. Feedstocks for first-generation (sugar and starch-based), second-generation (lignocellulosic biomass and energy crops), third-generation (algal-based) and fourth-generation (genetically modified algal biomass or crops) are discussed in detail. The study also assessed the process for ethanol production from various feedstocks, besides giving a holestic background knowledge on the bioconversion process, factors affecting bioethanol production, and various microorganisms involved in the fermentation process. Biotechnological tools also play a pivotal role in enhancing process efficiency and product yield. In adddition, most significant development in the field of genetic engineering and adaptive evolution are also highlighted.


Global biofuels policies on bioethanol production were presentedTechnological integrations of 1G, 2G, 3G and 4G bioethanol were discussedVarious factors affecting bioethanol production were mentionedTechno-economic analysis and LCA of bioethanol production are discussed.


Assuntos
Biotecnologia , Engenharia Genética , Amido , Etanol , Biocombustíveis , Biomassa , Fermentação , Produtos Agrícolas/metabolismo
14.
Indian J Pediatr ; 90(7): 708-717, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37264275

RESUMO

BACKGROUND: Allergic bronchopulmonary aspergillosis (ABPA) frequently complicates asthma. There is urgent need to develop evidence-based guidelines for the management of ABPA in children. The Evidence Based Guideline Development Group (EBGDG) of the Indian Academy of Pediatrics (IAP) National Respiratory Chapter (NRC) addressed this need. METHODS: The EBGDG shortlisted clinical questions relevant to the management of ABPA in asthma. For each question, the EBGDG undertook a systematic, step-wise evidence search for existing guidelines, followed by systematic reviews, followed by primary research studies. The evidence was collated, critically appraised, and synthesized. The EBGDG worked through the Evidence to Decision (EtD) framework, to formulate recommendations, using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. RESULTS: Seven clinical questions were prioritized, and the following recommendations formulated. (1) Children with poorly controlled asthma should be investigated for ABPA (conditional recommendation, moderate certainty of evidence). (2) Low dose steroid therapy regimen (0.5 mg/kg/d for the first 2 wk, followed by a progressive tapering) is preferable to higher dose regimens (conditional recommendation, very low certainty of evidence). (3) Oral steroid regimens longer than 16 wk (including tapering), should not be used (conditional recommendation, very low certainty of evidence). (4) Antifungals may or may not be added to steroid therapy as the evidence was neither in favour nor against (conditional recommendation, low certainty of evidence). (5) For clinicians using antifungal agents, the EBGDG recommends against using voriconazole instead of itraconazole (conditional recommendation, very low certainty of evidence). (6) No evidence-based recommendation could be framed for using pulse steroid therapy in preference to conventional steroid therapy. (7) Immunotherapy with biologicals including omalizumab or dupilumab is not recommended (conditional recommendation, very low certainty of evidence). CONCLUSIONS: This evidence-based guideline can be used by healthcare providers in diverse clinical settings.


Assuntos
Aspergilose Broncopulmonar Alérgica , Asma , Criança , Humanos , Adolescente , Aspergilose Broncopulmonar Alérgica/diagnóstico , Aspergilose Broncopulmonar Alérgica/tratamento farmacológico , Asma/complicações , Asma/tratamento farmacológico , Antifúngicos/uso terapêutico , Itraconazol/uso terapêutico , Voriconazol/uso terapêutico
16.
J Indian Assoc Pediatr Surg ; 28(1): 66-68, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36910298

RESUMO

Bronchogenic cyst is one of the rare developmental lung conditions. Depending on the location, it can cause significant compression of the mediastinal structures, especially airways leading to atelectasis, emphysema, wheezing, and stridor. Computerized tomography helps in the confirmation of diagnosis. Surgery is definitive management. We present a case of bronchogenic cyst which presented as emphysema leading to respiratory emergency in an infant.

17.
Environ Monit Assess ; 195(4): 451, 2023 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-36890356

RESUMO

Demographic outbursts and increased food demands invoke excessive use of pesticides in the agricultural field for increasing productivity which leads to the relentless decline of riverine health and its tributaries. These tributaries are connected to a plethora of point and non-point sources that transport pollutants including pesticides into the Ganga river's mainstream. Simultaneous climate change and lack of rainfall significantly increase pesticide concentration in the soil and water matrix of the river basin. This paper is intended to review the paradigm shift of pesticide pollution in the last few decades in the river Ganga and its tributaries. Along with this, a comprehensive review suggests the ecological risk assessment method which facilitates policy development, sustainable riverine ecosystem management, and decision-making. Before 2011, the total mixture of Hexachlorocyclohexane was found at 0.004-0.026 ng/mL in Hooghly, but now, the concentration has increased up to 0.465-4.132 ng/mL. Aftermath of critical review, we observed maximum residual commodities and pesticide contamination reported in Uttar Pradesh > West Bengal > Bihar > Uttara Khand possibly because of agricultural load, increasing settlement, and incompetency of sewage treatment plant in the reclamation of pesticide contamination.


Assuntos
Praguicidas , Poluentes Químicos da Água , Praguicidas/análise , Ecossistema , Monitoramento Ambiental , Poluentes Químicos da Água/análise , Rios , Medição de Risco
18.
Oncogene ; 42(8): 572-585, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36550359

RESUMO

The tumour suppressor BRCA1-associated protein 1 (BAP1) is the most frequently mutated cancer gene in mesothelioma. Here we report novel functions for BAP1 in mitotic progression highlighting the relationship between BAP1 and control of genome stability in mesothelioma cells with therapeutic implications. Depletion of BAP1 protein induced proteasome-mediated degradation of BRCA1 in mesothelioma cells while loss of BAP1 correlated with BRCA1 loss in mesothelioma patient tumour samples. BAP1 loss also led to mitotic defects that phenocopied the loss of BRCA1 including spindle assembly checkpoint failure, centrosome amplification and chromosome segregation errors. However, loss of BAP1 also led to additional mitotic changes that were not observed upon BRCA1 loss, including an increase in spindle length and enhanced growth of astral microtubules. Intriguingly, these consequences could be explained by loss of expression of the KIF18A and KIF18B kinesin motors that occurred upon depletion of BAP1 but not BRCA1, as spindle and astral microtubule defects were rescued by re-expression of KIF18A and KIF18B, respectively. We therefore propose that BAP1 inactivation causes mitotic defects through BRCA1-dependent and independent mechanisms revealing novel routes by which mesothelioma cells lacking BAP1 may acquire genome instability and exhibit altered responses to microtubule-targeted agents.


Assuntos
Proteína BRCA1 , Neoplasias Pulmonares , Mesotelioma Maligno , Mesotelioma , Proteínas Supressoras de Tumor , Ubiquitina Tiolesterase , Humanos , Proteína BRCA1/genética , Proteína BRCA1/metabolismo , Segregação de Cromossomos , Genes Supressores de Tumor , Cinesinas/genética , Cinesinas/metabolismo , Neoplasias Pulmonares/patologia , Mesotelioma/patologia , Mesotelioma Maligno/genética , Mesotelioma Maligno/metabolismo , Microtúbulos/metabolismo , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo , Ubiquitina Tiolesterase/genética , Ubiquitina Tiolesterase/metabolismo
19.
Physiol Mol Biol Plants ; 29(12): 2021-2033, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38222276

RESUMO

The present study is based on the application of H2S as an exogenous antidote in Spinacia oleracea (spinach) plants grown in Cd-contaminated (50 ppm) soil. The different doses of H2S in the form of NaHS (10, 50, 100, 200, and 500 µM) have been applied as a foliar spray to regulate the physiological attributes under Cd toxicity. Over to control, the plants grown in Cd alone showed a reduction in the fresh biomass by 48% with more production of oxidative biomarkers (H2O2, SOR, and MDA content) and antioxidative enzymes (SOD, POD, APX, and GR). Further, with the exogenous application of H2S, among all the doses the fresh biomass was found to be maximally increased at 100 µM dose by 76%, and the Cd content was reduced significantly by 25% in the shoot compared to plants grown in Cd treated soil alone. With the decrease in Cd content in the shoot, the production of H2O2, SOR, and MDA content was reduced by 52%, 40%, and 38% respectively, at 100 µM compared to the plants grown in Cd-treated soil. The activities of estimated antioxidative enzymes showed a reduction in their activities up to 100 µM. Whereas, Glutathione reductase (GR) and Phytochelatins (PCs) showed different trends with their higher values in plants treated with NaHS in the presence of Cd. At 100 µM the GR and PCs, respectively showed 48% and 37% increment over Cd-treated plants alone. At this dose, the relative expression of SOD, POD, APX, GR, and PCS5 (Phytochelatin synthetase enzyme) genes, and other functional activities (SEM and fluorescence kinetics) supported the best performance of plants at 100 µM. Therefore, among all the doses, 100 µM dose of H2S has significantly reduced the Cd toxicity by maintaining the growth and other functional traits of plants. The correlation analysis also supported the result by showing a relationship between H2S application and Cd uptake. So, with this strategy, the plants grown in metal-contaminated fields can be improved qualitatively as well as quantitatively. With further experimentation, the mode of application could be explored to increase its efficiency and to promote this strategy at a wider scale. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-023-01389-3.

20.
J Vis Exp ; (188)2022 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-36342129

RESUMO

The biomechanical properties of the trachea directly affect the airflow and contribute to the biological function of the respiratory system. Understanding these properties is critical to understanding the injury mechanism in this tissue. This protocol describes an experimental approach to study the stress-relaxation behavior of porcine trachea that were pre-stretched to 0% or 10% strain for 300 s, followed by mechanical tensile loading until failure. This study provides details of the experimental design, data acquisition, analyses, and preliminary results from the porcine tracheae biomechanical testing. Using the detailed steps provided in this protocol and the data analysis MATLAB code, future studies can investigate the time-dependent viscoelastic behavior of trachea tissue, which is critical to understanding its biomechanical responses during physiological, pathological, and traumatic conditions. Furthermore, in-depth studies of the biomechanical behavior of the trachea will critically aid in improving the design of related medical devices such as endotracheal implants that are widely used during surgeries.


Assuntos
Fenômenos Fisiológicos Respiratórios , Traqueia , Suínos , Animais , Traqueia/cirurgia , Traqueia/fisiologia , Resistência à Tração , Estresse Mecânico , Fenômenos Biomecânicos , Elasticidade , Viscosidade
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