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1.
Proc Natl Acad Sci U S A ; 120(5): e2211347120, 2023 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-36701365

RESUMEN

Viscoelastic flows are pervasive in a host of natural and industrial processes, where the emergence of nonlinear and time-dependent dynamics regulates flow resistance, energy consumption, and particulate dispersal. Polymeric stress induced by the advection and stretching of suspended polymers feeds back on the underlying fluid flow, which ultimately dictates the dynamics, instability, and transport properties of viscoelastic fluids. However, direct experimental quantification of the stress field is challenging, and a fundamental understanding of how Lagrangian flow structure regulates the distribution of polymeric stress is lacking. In this work, we show that the topology of the polymeric stress field precisely mirrors the Lagrangian stretching field, where the latter depends solely on flow kinematics. We develop a general analytical expression that directly relates the polymeric stress and stretching in weakly viscoelastic fluids for both nonlinear and unsteady flows, which is also extended to special cases characterized by strong kinematics. Furthermore, numerical simulations reveal a clear correlation between the stress and stretching field topologies for unstable viscoelastic flows across a broad range of geometries. Ultimately, our results establish a connection between the Eulerian stress field and the Lagrangian structure of viscoelastic flows. This work provides a simple framework to determine the topology of polymeric stress directly from readily measurable flow field data and lays the foundation for directly linking the polymeric stress to flow transport properties.

2.
Cell Mol Life Sci ; 81(1): 140, 2024 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-38485771

RESUMEN

The importance of mechanosensory transduction pathways in cellular signalling has prominently come to focus in the last decade with the discovery of the Piezo ion channel family. Mechanosignaling involving Piezo1 ion channels in the function of the heart and cardiovascular system has only recently been identified to have implications for cardiovascular physiology and pathophysiology, in particular for heart failure (i.e., hypertrophy or dilative cardiomyopathy). These results have emphasized the need for higher throughput methods to study single-cell cardiovascular mechanobiology with the aim of identifying new targets for therapeutic interventions and stimulating the development of new pharmacological agents. Here, we present a novel method to assess mechanosignaling in adherent cardiac cells (murine HL-1 cell line) using a combination of isotropic cell stretch application and simultaneous Ca2+ fluorescence readout with quantitative analysis. The procedure implements our IsoStretcher technology in conjunction with a single-cell- and population-based analysis of Ca2+ signalling by means of automated image registration, cell segmentation and analysis, followed by automated classification of single-cell responses. The method is particularly valuable for assessing the heterogeneity of populations with distinct cellular responses to mechanical stimulation and provides more user-independent unbiased drug response classifications.


Asunto(s)
Canales Iónicos , Mecanotransducción Celular , Ratones , Animales , Canales Iónicos/metabolismo , Transducción de Señal , Corazón , Línea Celular
3.
Proc Natl Acad Sci U S A ; 119(8)2022 02 22.
Artículo en Inglés | MEDLINE | ID: mdl-35131899

RESUMEN

Due to the enormous economic, health, and social costs of the COVID-19 pandemic, there are high expected social returns to investing in parallel in multiple approaches to accelerating vaccination. We argue there are high expected social returns to investigating the scope for lowering the dosage of some COVID-19 vaccines. While existing evidence is not dispositive, available clinical data on the immunogenicity of lower doses combined with evidence of a high correlation between neutralizing antibody response and vaccine efficacy suggests that half or even quarter doses of some vaccines could generate high levels of protection, particularly against severe disease and death, while potentially expanding supply by 450 million to 1.55 billion doses per month, based on supply projections for 2021. An epidemiological model suggests that, even if fractional doses are less effective than standard doses, vaccinating more people faster could substantially reduce total infections and deaths. The costs of further testing alternative doses are much lower than the expected public health and economic benefits. However, commercial incentives to generate evidence on fractional dosing are weak, suggesting that testing may not occur without public investment. Governments could support either experimental or observational evaluations of fractional dosing, for either primary or booster shots. Discussions with researchers and government officials in multiple countries where vaccines are scarce suggests strong interest in these approaches.


Asunto(s)
Vacunas contra la COVID-19/provisión & distribución , COVID-19/prevención & control , Inmunización Secundaria/métodos , Modelos Estadísticos , Vacunación/métodos , COVID-19/inmunología , COVID-19/mortalidad , COVID-19/virología , Vacunas contra la COVID-19/administración & dosificación , Vacunas contra la COVID-19/economía , Países Desarrollados , Países en Desarrollo , Esquema de Medicación , Humanos , Inmunización Secundaria/economía , Uso Fuera de lo Indicado , SARS-CoV-2/efectos de los fármacos , SARS-CoV-2/inmunología , SARS-CoV-2/patogenicidad , Análisis de Supervivencia , Vacunación/economía
4.
Small ; 20(4): e2302404, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37735983

RESUMEN

Strain gradients widely exist in development and physiological activities. The directional movement of cells is essential for proper cell localization, and directional cell migration in responses to gradients of chemicals, rigidity, density, and topography of extracellular matrices have been well-established. However; it is unclear whether strain gradients imposed on cells are sufficient to drive directional cell migration. In this work, a programmable uniaxial cell stretch device is developed that creates controllable strain gradients without changing substrate stiffness or ligand distributions. It is demonstrated that over 60% of the single rat embryonic fibroblasts migrate toward the lower strain side in static and the 0.1 Hz cyclic stretch conditions at ≈4% per mm strain gradients. It is confirmed that such responses are distinct from durotaxis or haptotaxis. Focal adhesion analysis confirms higher rates of contact area and protrusion formation on the lower strain side of the cell. A 2D extended motor-clutch model is developed to demonstrate that the strain-introduced traction force determines integrin fibronectin pairs' catch-release dynamics, which drives such directional migration. Together, these results establish strain gradient as a novel cue to regulate directional cell migration and may provide new insights in development and tissue repairs.


Asunto(s)
Quimiotaxis , Matriz Extracelular , Ratas , Animales , Movimiento Celular , Adhesiones Focales , Adhesión Celular
5.
Am J Physiol Regul Integr Comp Physiol ; 327(4): R389-R399, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-39102463

RESUMEN

Increasing evidence suggests that activation of muscle nerve afferents may inhibit central motor drive, affecting contractile performance of remote exercising muscles. Although these effects are well documented for metaboreceptors, very little is known about the activation of mechano- and mechanonociceptive afferents on performance fatigability. Therefore, the purpose of the present study was to examine the influence of mechanoreceptors and nociceptors on performance fatigability. Eight healthy young males undertook four randomized experimental sessions on separate occasions in which the experimental knee extensors were the following: 1) resting (CTRL), 2) passively stretched (ST), 3) resting with delayed onset muscle soreness (DOMS), or 4) passively stretched with DOMS (DOMS+ST), whereas the contralateral leg performed an isometric time to task failure (TTF). Changes in maximal voluntary contraction (ΔMVC), potentiated twitch force (ΔQtw,pot), and voluntary muscle activation (ΔVA) were also assessed. TTF was reduced in DOMS+ST (-43%) and ST (-29%) compared with CTRL. DOMS+ST also showed a greater reduction of VA (-25% vs. -8%, respectively) and MVC compared with CTRL (-28% vs. -45%, respectively). Rate of perceived exertion (RPE) was significantly increased at the initial stages (20-40-60%) of the TTF in DOMS+ST compared with all conditions. These findings indicate that activation of mechanosensitive and mechanonociceptive afferents of a muscle with DOMS reduces TTF of the contralateral homologous exercising limb, in part, by reducing VA, thereby accelerating mechanisms of central fatigue.NEW & NOTEWORTHY We found that activation of mechanosensitive and nociceptive nerve afferents of a rested muscle group experiencing delayed onset muscle soreness was associated with reduced exercise performance of the homologous exercising muscles of the contralateral limb. This occurred with lower muscle voluntary activation of the exercising muscle at the point of task failure.


Asunto(s)
Mecanorreceptores , Fatiga Muscular , Músculo Esquelético , Mialgia , Nociceptores , Humanos , Masculino , Músculo Esquelético/inervación , Músculo Esquelético/fisiología , Mecanorreceptores/fisiología , Mecanorreceptores/metabolismo , Adulto Joven , Nociceptores/fisiología , Mialgia/fisiopatología , Adulto , Ejercicio Físico/fisiología , Contracción Muscular , Contracción Isométrica
6.
Mult Scler ; 30(1): 89-102, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38140847

RESUMEN

BACKGROUND: Clinical practice, expert opinion, and evidence-based guidelines recommend daily stretching as first-line treatment for multiple sclerosis (MS) spasticity, but this has not been evaluated by fully powered clinical trials. OBJECTIVE: To determine whether MS Spasticity: Take Control (STC), a guideline-based program of spasticity education and stretching exercises has different effects on the impact of spasticity than a control program of different spasticity education and range of motion (ROM) exercises. METHODS: Ambulatory people with self-reported MS spasticity were randomly assigned to STC or ROM, delivered in same duration, facilitator-led, group classes, face-to-face (F2F) initially and later virtually, due to coronavirus disease 2019 (COVID-19). Multiple Sclerosis Spasticity Scale (MSSS) scores were compared between groups at 1 (primary outcome) and 6 months after interventions. RESULTS: A total of 231 people enrolled. There was no significant difference in MSSS scores between STC and ROM at 1 month (mean difference = 0.28, 95% (confidence interval (CI)) = [-9.45 to 10.01], p = 0.955). There were significant group mean improvements in MSSS scores and most other outcomes at 1 and 6 months. CONCLUSION: Education with stretching exercises, the first-line recommended treatment for MS spasticity, and education with ROM exercises may both improve MS spasticity to a similar degree. This study debunks the belief that stretching is essential to managing MS spasticity.


Asunto(s)
Esclerosis Múltiple , Espasticidad Muscular , Humanos , Espasticidad Muscular/etiología , Espasticidad Muscular/terapia , Terapia por Ejercicio , Esclerosis Múltiple/complicaciones , Esclerosis Múltiple/terapia , Autoinforme
7.
Cell Commun Signal ; 22(1): 93, 2024 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-38302971

RESUMEN

BACKGROUND: Physical exercise directly stretching the peripheral nerve promotes nerve regeneration; however, its action mechanism remains elusive. Our present study aimed to investigate the effects of mechanosensitive channel of large conductance (MscL) activated by mechanical stretching on the cultured Schwann cells (SCs) and explore the possible mechanism. METHODS: Primary SCs from neonatal mice at 3-5 days of age were derived and transfected with the lentivirus vector expressing a mutant version of MscL, MscL-G22S. We first detected the cell viability and calcium ion (Ca2+) influx in the MscL-G22S-expressing SCs with low-intensity mechanical stretching and the controls. Proteomic and energy metabolomics analyses were performed to investigate the comprehensive effects of MscL-G22S activation on SCs. Measurement of glycolysis- and oxidative phosphorylation-related molecules and ATP production were respectively performed to further validate the effects of MscL-G22S activation on SCs. Finally, the roles of phosphatidylinositol-3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling pathway in the mechanism of energy metabolism modulation of SCs by MscL-G22S activation was investigated. RESULTS: Mechanical stretching-induced MscL-G22S activation significantly increased the cell viability and Ca2+ influx into the SCs. Both the proteomic and targeted energy metabolomics analysis indicated the upregulation of energy metabolism as the main action mechanism of MscL-G22S-activation on SCs. MscL-G22S-activated SCs showed significant upregulation of glycolysis and oxidative phosphorylation when SCs with stretching alone had only mild upregulation of energy metabolism than those without stimuli. MscL-G22S activation caused significant phosphorylation of the PI3K/AKT/mTOR signaling pathway and upregulation of HIF-1α/c-Myc. Inhibition of PI3K abolished the MscL-G22S activation-induced upregulation of HIF-1α/c-Myc signaling in SCs and reduced the levels of glycolysis- and oxidative phosphorylation-related substrates and mitochondrial activity. CONCLUSION: Mechanical stretching activates MscL-G22S to significantly promote the energy metabolism of SCs and the production of energic substrates, which may be applied to enhance nerve regeneration via the glia-axonal metabolic coupling.


Asunto(s)
Proteínas Proto-Oncogénicas c-akt , Transducción de Señal , Ratones , Animales , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Regulación hacia Arriba , Proteómica , Proteínas Proto-Oncogénicas c-myc/metabolismo , Glucólisis , Células de Schwann/metabolismo , Fosfatidilinositol 3-Quinasa/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Estrés Oxidativo , Mamíferos/metabolismo
8.
Cell Commun Signal ; 22(1): 419, 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39192354

RESUMEN

BACKGROUND: Intervertebral disc (IVD) degeneration is a multifactorial pathological process resulting in the dysregulation of IVD cell activity. The catabolic shift observed in IVD cells during degeneration leads to increased inflammation, extracellular matrix (ECM) degradation, aberrant intracellular signaling and cell loss. Importantly, these pathological processes are known to be interconnected and to collectively contribute to the progression of the disease. MicroRNAs (miRNAs) are known as strong post-transcriptional regulators, targeting multiple genes simultaneously and regulating numerous intracellular pathways. Specifically, miR-155-5p has been of particular interest since it is known as a pro-inflammatory mediator and contributing factor to diseases like cancer and osteoarthritis. This study investigated the role of miR-155-5p in IVD degeneration with a specific focus on inflammation and mechanosensing. METHODS: Gain- and loss-of-function studies were performed through transfection of human Nucleus pulposus (NP) and Annulus fibrosus (AF) cells isolated from degenerated IVDs with miR-155-5p mimics, inhibitors or their corresponding non-targeting control. Transfected cells were then subjected to an inflammatory environment or mechanical loading. Conditioned media and cell lysates were collected for phosphorylation and cytokine secretion arrays as well as gene expression analysis. RESULTS: Increased expression of miR-155-5p in AF cells resulted in significant upregulation of interleukin (IL)-8 cytokine secretion during cyclic stretching and a similar trend in IL-6 secretion during inflammation. Furthermore, miR-155-5p mimics increased the expression of the brain-derived neurotrophic factor (BDNF) in AF cells undergoing cyclic stretching. In NP cells, miR-155-5p gain-of-function resulted in the activation of the mitogen-activated protein kinase (MAPK) signaling pathway through increased phosphorylation of p38 and p53. Lastly, miR-155-5p inhibition caused a significant increase in the anti-inflammatory cytokine IL-10 in AF cells and the tissue inhibitor of metalloproteinases (TIMP)-4 in NP cells respectively. CONCLUSION: Overall, these results show that miR-155-5p contributes to IVD degeneration by enhancing inflammation through pro-inflammatory cytokines and MAPK signaling, as well as by promoting the catabolic shift of AF cells during mechanical loading. The inhibition of miR-155-5p may constitute a potential therapeutic approach for IVD degeneration and low back pain.


Asunto(s)
Inflamación , Degeneración del Disco Intervertebral , MicroARNs , MicroARNs/genética , MicroARNs/metabolismo , Degeneración del Disco Intervertebral/genética , Degeneración del Disco Intervertebral/metabolismo , Degeneración del Disco Intervertebral/patología , Humanos , Inflamación/genética , Inflamación/patología , Inflamación/metabolismo , Núcleo Pulposo/metabolismo , Núcleo Pulposo/patología , Masculino , Soporte de Peso , Persona de Mediana Edad , Femenino , Anillo Fibroso/metabolismo , Anillo Fibroso/patología
9.
J Fluoresc ; 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38888659

RESUMEN

The current model offers valuable insights for materials science, heat exchangers, renewable energy production, nanotechnology, manufacturing, medicinal treatments, and environmental engineering. The findings of this study have the potential to improve material design, increase heat transfer efficiency across various systems, enhance energy conversion processes, and drive advancements in nanotechnology, medicinal treatments, and engineering design. The goal of the current research is to analyze the effects of thermal radiation and the volume fraction of nanoparticles in MoS2-Ag/engine oil-based hybrid nanofluid flow passing through a cylinder. After performing a substantial similarity transformation, the nonlinear dimensionless framework is recast as ODEs. The Yamada-Ota and Xue models are then applied to the dimensionless equation setup, which is numerically solved using the BVP4C approach. The resulting velocity and temperature fields, corresponding to various parameters, are examined and compared across both models. This investigation demonstrates a significant variation in heat transfer rates between the Yamada-Ota and Xue models, with the former having a larger impact. The velocity and temperature fields decrease as the magnetic field parameter increases in both nanofluids. However, as the magnetic field parameter values grow, the velocity fields in the two nanofluids behave differently. The Yamada-Ota and Xue models are used to determine the behavior of the hybrid nanofluid flow over a nonlinear extended cylinder. In all situations, the velocity and temperature fields exhibit superior decay characteristics.

10.
Macromol Rapid Commun ; 45(6): e2300624, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38018318

RESUMEN

Conjugated polymers exhibit excellent electrical and mechanical properties when their molecular weight (Mw) is above the critical molecular weight (Mc). The microstructural changes of polymers under strain are crucial to establish a structure-performance relationship. Herein, the tensile deformation of P(NDI2OD-T2) is visualized, and cracks are revealed either along the (100) crystal plane of side chain packing or along the main chain direction which depends on the Mw is below or above the Mc. When Mw < Mc, the film cracks along the (100) plane under small strains. When Mw > Mc, the polymer chains first undergo stretch-induced orientation and then fracture along the main chain direction at large strains. This is attributed to the fact that the low Mw film exhibits large crystalline domains and the absence of interdomain connectivity, which are vulnerable to mechanical stress. In contrast, the high Mw film displays a nearly amorphous morphology with adequate entanglements, the molecular chains can endure stresses in the stretching direction to release substantial strain energy under greater mechanical deformation. Therefore, the film with Mw > Mc exhibits the optimal electrical and mechanical performances simultaneously, i.e., the electron mobility is retained under 100% strain and after 100 stretching-releasing cycles.


Asunto(s)
Polímeros , Peso Molecular , Polímeros/química , Estrés Mecánico
11.
Macromol Rapid Commun ; 45(16): e2400145, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38776530

RESUMEN

Mechanochromic materials have received broad research interests recently, owing to its ability to monitor the in situ stress/strain in polymer materials in a straightforward way. However, one major setback that hinders the practical application of these materials is their low sensitivity toward tensile strain. Here a new strategy for pre-stretching of the mechanochromic agent in a polymer film on the molecular scale, which can effectively enhance the mechanochromic sensitivity of a polymer film toward tensile strain, is shown. In situ fluorescent measurement during tensile test shows an early activation of the mechanochromic agent at tensile strain as low as 50%. The pre-stretching effect is realized by first inducing ring-opening of the mechanochromic agent by molecular functionalization, and then compelling the ring-closure process in the cured film by elevated temperature. This post-curing ring-closure process will result in pre-stretched mechanochromic agent in a crosslinked network. The mechanism for mechanochromic activation of polymer films with different composition is elaborated by visco-elastic measurements, and the effect of pre-stretching is further confirmed by films with other compositions. Combined with the simplicity of the method developed, this work could offer an alternative strategy to enhance the sensitivity of different mechanochromic agents toward tensile strain.


Asunto(s)
Polímeros , Resistencia a la Tracción , Polímeros/química , Estructura Molecular , Estrés Mecánico
12.
Pediatr Nephrol ; 2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-38926177

RESUMEN

BACKGROUND: Chronic kidney disease (CKD) is a prevalent health issue that can have detrimental effects on the quality of life (QoL) of children. Nevertheless, with adequate management and support, many children with CKD can have satisfying lives. The study aimed to investigate the effect of muscle stretching and isometric exercises on QoL of children undergoing hemodialysis. METHODS: Sixty-eight children aged 6-18 years with kidney failure undergoing hemodialysis at Assiut University Children Hospital were included. They were randomly assigned to two groups. The study group received a 40-min exercise program three times per week for 2 months, while the control group received routine hospital care. For outcome measures, two tools were used: a simple questionnaire sheet for personal and medical data and PedsQL™ scale. RESULTS: After 2 months of exercise, it was shown that most children in the study group (66.7%) had good QoL, in contrast to only 3.3% in the control group, with a highly statistically significant variation between the two examined groups pertaining to the health-related QoL scale (P value = 0.001) after exercise. CONCLUSION: The intensity of care for children on hemodialysis has a distinguished impact upon their quality of life. The implementation of muscle stretching and isometric exercises during hemodialysis represents an important aspect of such care that may be associated with significant improvement in all domains of QoL. Children undergoing hemodialysis need well-organized programs that cover all physical and psychological aspects with smart time manipulation and increased attention from their staff.

13.
Somatosens Mot Res ; 41(3): 159-167, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38289007

RESUMEN

AIM: This study aimed to compare the acute effects of different methods on ankle joint range of motion (ROM) in older adults. MATERIALS AND METHODS: Seventy-eight older adults were randomly divided into three groups. After the warming-up, static stretching, proprioceptive neuromuscular facilitation (PNF) contract-relax, and roller massage were applied, at the same period. Before application, immediately after, 10 and 20 min after application, ankle joint dorsiflexion ROM was measured in the weight-bearing position. RESULTS: No statistically significant difference between the groups in demographic characteristics and baseline ankle ROM (p = 0.413). In all groups, post-application measurements revealed increased ankle joint motion (p < 0.0125). Groups were compared, and a statistically significant difference between the three groups was found (p < 0.05). There was no significant difference in the change of ROM between the Static Stretching and PNF Stretching Groups in the change of ROM group comparisons (p = 0.089). There was a statistically significant difference in ROM changes Roller Massage Group and both Static Stretching and the PNF Stretching Group (p = 0.001). CONCLUSION: The acute effects of roller massage, on ankle ROM, were superior to static and PNF stretching. The application of roller massage, which was shown to be an effective method for increasing ROM, can be safely applied in physiotherapy programs for older adults.


Asunto(s)
Articulación del Tobillo , Masaje , Ejercicios de Estiramiento Muscular , Rango del Movimiento Articular , Humanos , Rango del Movimiento Articular/fisiología , Masculino , Femenino , Anciano , Articulación del Tobillo/fisiología , Masaje/métodos , Ejercicios de Estiramiento Muscular/fisiología , Persona de Mediana Edad
14.
Mol Cell ; 64(6): 1035-1047, 2016 12 15.
Artículo en Inglés | MEDLINE | ID: mdl-27889453

RESUMEN

The molecular machinery responsible for DNA replication, the replisome, must efficiently coordinate DNA unwinding with priming and synthesis to complete duplication of both strands. Due to the anti-parallel nature of DNA, the leading strand is copied continuously, while the lagging strand is produced by repeated cycles of priming, DNA looping, and Okazaki-fragment synthesis. Here, we report a multidimensional single-molecule approach to visualize this coordination in the bacteriophage T7 replisome by simultaneously monitoring the kinetics of loop growth and leading-strand synthesis. We show that loops in the lagging strand predominantly occur during priming and only infrequently support subsequent Okazaki-fragment synthesis. Fluorescence imaging reveals polymerases remaining bound to the lagging strand behind the replication fork, consistent with Okazaki-fragment synthesis behind and independent of the replication complex. Individual replisomes display both looping and pausing during priming, reconciling divergent models for the regulation of primer synthesis and revealing an underlying plasticity in replisome operation.


Asunto(s)
Bacteriófago T7/genética , ADN Primasa/genética , Replicación del ADN , ADN Viral/genética , Bacteriófago T7/metabolismo , Bacteriófago T7/ultraestructura , ADN/biosíntesis , ADN/genética , ADN Primasa/metabolismo , ADN Primasa/ultraestructura , ADN Viral/metabolismo , ADN Viral/ultraestructura , Cinética , Imagen Individual de Molécula/métodos , Imagen de Lapso de Tiempo/métodos
15.
Artif Organs ; 48(9): 943-960, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38887912

RESUMEN

BACKGROUND: Tissue stimulations greatly affect cell growth, phenotype, and function, and they play an important role in modeling tissue physiology. With the goal of understanding the cellular mechanisms underlying the response of tissues to external stimulations, in vitro models of tissue stimulation have been developed in hopes of recapitulating in vivo tissue function. METHODS: Herein we review the efforts to create and validate tissue stimulators responsive to electrical or mechanical stimulation including tensile, compression, torsion, and shear. RESULTS: Engineered tissue platforms have been designed to allow tissues to be subjected to selected types of mechanical stimulation from simple uniaxial to humanoid robotic stain through equal-biaxial strain. Similarly, electrical stimulators have been developed to apply selected electrical signal shapes, amplitudes, and load cycles to tissues, lending to usage in stem cell-derived tissue development, tissue maturation, and tissue functional regeneration. Some stimulators also allow for the observation of tissue morphology in real-time while cells undergo stimulation. Discussion on the challenges and limitations of tissue simulator development is provided. CONCLUSIONS: Despite advances in the development of useful tissue stimulators, opportunities for improvement remain to better reproduce physiological functions by accounting for complex loading cycles, electrical and mechanical induction coupled with biological stimuli, and changes in strain affected by applied inputs.


Asunto(s)
Ingeniería de Tejidos , Humanos , Ingeniería de Tejidos/métodos , Animales , Estimulación Eléctrica/métodos , Estrés Mecánico , Fenómenos Biomecánicos
16.
Cryobiology ; : 104958, 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39243925

RESUMEN

Adherent cell systems are usually dissociated before being cryopreserved, as standard protocols are established for cells in suspension. The application of standard procedures to more complex systems, sensitive to dissociation, such as adherent monolayers, especially comprising mature cell types, or tissues, remains unsatisfactory. Uncontrolled cell detachment due to intracellular tensile stress, membrane ruptures and damages of adhesion proteins are common during freezing and thawing of cell monolayers. However, many therapeutically relevant cell systems grow adherently to develop their native morphology and functionality, but lose their integrity after dissociation. The hypothesis is that cells on stretchable substrates have a more adaptable cytoskeleton and membrane, reducing cryopreservation-induced stress. Our studies investigate the influence of stretchable surfaces on the cryopreservation of adherent cells to avoid harmful dissociation and expedite post-thawing cultivation of functional cells. A stretching apparatus for defined radial stretching, consisting of silicone vessels and films with specific surface textures for cell culture, were developed. Adherent human umbilical cord mesenchymal stem cells (hUC-MSCs) were cultivated on a stretched silicone film within the vessel, forming a monolayer that were compressed by relaxation, while remaining attached to the relaxed film. Compressed hUC-MSCs, which were cryopreserved adherently showed higher viability and less detachment after thawing compared to control cells without compression. Within three to seven days post-thawing, the hUC-MSCs recovered, and the monolayer reformed. These experiments support the hypothesis that cryopreservation success of adherent cell systems is enhanced by improved adaptability of the cytoskeleton and cell membrane, opening up new approaches in cryobiotechnology.

17.
Scand J Med Sci Sports ; 34(8): e14708, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39165228

RESUMEN

OBJECTIVES: Flexibility is recognized as one of the components of physical fitness and commonly included as part of exercise prescriptions for all ages. However, limited data exist regarding the relationship between flexibility and survival. We evaluated the sex-specific nature and magnitude of the associations between body flexibility and natural and non-COVID-19 mortality in a middle-aged cohort of men and women. DESIGN: Prospective cohort study. METHODS: Anthropometric, health and vital data from 3139 (66% men) individuals aged 46-65 years spanning from March 1994 to October 2022 were available. A body flexibility score, termed Flexindex, was derived from a combination of 20 movements (scored 0-4) involving seven different joints, resulting in a score range of 0-80. Kaplan-Meier survival curves were obtained, and unadjusted and adjusted hazard ratios (HRs) for mortality estimated. RESULTS: During a mean follow-up of 12.9 years, 302 individuals (9.6%) comprising 224 men/78 women died. Flexindex was 35% higher in women compared to men (mean ± SD: 41.1 ± 9.4 vs. 30.5 ± 8.7; p < 0.001) and exhibited an inverse relationship with mortality risk in both sexes (p < 0.001). Following adjustment for age, body mass index, and health status, the HR (95% CI) for mortality comparing upper and bottom of distributions of Flexindex were 1.87 (1.50-2.33; p < 0.001) for men and 4.78 (1.23-31.71; p = 0.047) for women. CONCLUSIONS: A component of physical fitness-body flexibility-as assessed by the Flexindex is strongly and inversely associated with natural and non-COVID-19 mortality risk in middle-aged men and women. Future studies should assess whether training-induced flexibility gains are related to longer survival.


Asunto(s)
Aptitud Física , Humanos , Masculino , Femenino , Persona de Mediana Edad , Estudios Prospectivos , Anciano , Factores Sexuales , Rango del Movimiento Articular , Estimación de Kaplan-Meier , Modelos de Riesgos Proporcionales , Mortalidad , COVID-19/mortalidad
18.
Eur J Appl Physiol ; 124(6): 1885-1893, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38240811

RESUMEN

OBJECTIVES: Current research suggests static stretch-induced maximal strength increases and muscle hypertrophy with potential to substitute resistance-training routines. However, most studies investigated the plantar flexors. This study explored the effects of a static stretching program on maximal strength, hypertrophy and flexibility of the pectoralis major and compared the effects with those of traditional resistance training. METHODS: Eighty-one (81) active participants were allocated to either a static stretching, strength-training or control group. Pectoralis stretching was applied 15 min/day, 4 days per week for 8 weeks, while resistance training trained 3 days per week, 5 × 12 repetitions. RESULTS: There was an increase in all parameters (strength: p < 0.001, ƞ2 = 0.313, muscle thickness: p < 0.001, ƞ2 = 0.157-0.264, flexibility: p < 0.001, ƞ2 = 0.316) and a time*group interaction (strength: p = 0.001, ƞ2 = 0.154, muscle thickness: p = 0.008-0.001, ƞ2 = 0.117-0.173, flexibility: p < 0.001, ƞ2 = 0.267). Post-hoc testing showed no difference between both intervention groups regarding maximal strength and muscle thickness (p = 0.905-0.983, d = 0.036-0.087), while flexibility increased in the stretching group (p = 0.001, d = 0.789). CONCLUSION: Stretching showed increases in maximal strength and hypertrophy, which were comparable with commonly used resistance training. Based on current literature, the influence of mechanical tension as the underlying mechanism is discussed. Furthermore, as equipment and comparatively long stretching durations are requested to induce meaningful strength increases in recreationally active participants, practical application seems limited to special circumstances.


Asunto(s)
Fuerza Muscular , Ejercicios de Estiramiento Muscular , Músculos Pectorales , Rango del Movimiento Articular , Entrenamiento de Fuerza , Humanos , Entrenamiento de Fuerza/métodos , Fuerza Muscular/fisiología , Músculos Pectorales/fisiología , Masculino , Femenino , Adulto , Rango del Movimiento Articular/fisiología , Adulto Joven
19.
Eur J Appl Physiol ; 124(3): 793-803, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37702788

RESUMEN

PURPOSE: Non-muscular tissue stiffness is assumed to have a negative impact on joint flexibility, and a reduction in non-muscular tissue stiffness may be important, especially in older adults. The present study aimed to compare the acute effects of static stretching on non-muscular tissue stiffness between older and young adults and to investigate whether a decrease in tissue stiffness improves joint flexibility. METHODS: Twenty older (62-83 years) and 20 young (21-24 years) males participated. Ankle dorsiflexion static stretching (five sets of 90 s each) was performed, and before and after stretching, the ankle dorsiflexion range of motion (RoM), passive ankle joint stiffness, and shear wave speed (SWS) (an index of stiffness) of the sciatic nerve, tibial nerve, and posterior thigh fascia were measured. RESULTS: Stretching led to an increase in RoM and a decrease in passive joint stiffness in both groups (P < 0.001) with no significant between-group differences (P ≥ 0.055). The between-group difference in the effect of stretching on SWS was evident only for the sciatic nerve, and a decline in sciatic nerve SWS was only observed in the older adult group (pre-stretching: 2.5 ± 0.3 m/s; post-stretching: 2.3 ± 0.4 m/s; P = 0.027). A significant positive repeated-measures correlation was observed between the sciatic nerve SWS and passive joint stiffness (P = 0.014, rrm = 0.540). CONCLUSION: The reduction in sciatic nerve stiffness by stretching was noticeable in older men and led to improved joint flexibility. These findings may provide insight into tissue adaptation by stretching and may be used to explore effective exercises for improving joint flexibility in older adults.


Asunto(s)
Ejercicios de Estiramiento Muscular , Masculino , Adulto Joven , Humanos , Anciano , Músculo Esquelético/fisiología , Fascia , Muslo , Rango del Movimiento Articular/fisiología , Articulación del Tobillo/fisiología , Torque
20.
Eur J Appl Physiol ; 124(9): 2533-2545, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38918221

RESUMEN

PURPOSE: The widespread and health-detrimental sleep disorders have resulted in stretching exercises being investigated as a non-drug solution for enhanced sleep quality. However, a comprehensive understanding of the impact of stretching exercises on individuals with sleep disorders is lacking. METHODS: This scoping review systematically maps the existing literature and identifies research gaps on the impact of stretching exercises on sleep quality in individuals with sleep disorders. RESULTS: Sixteen eligible studies were included, where the weighted mean changes indicate a positive trend in sleep quality improvement, ranging from trivial to very large magnitudes. However, concerning the individual study results only 5 out of 16 studies reported significant improvements. Notable enhancements include a small 1.22% overall sleep quality improvement, a large 6.51% reduction in insomnia severity, a large 8.88% increase in sleep efficiency, a moderate 4.36% decrease in sleep onset latency, a large 8.27% decrease in wake after sleep onset, and a very large 14.70% improvement in total sleep time. Trivial changes are noted in sleep duration (0.58%), sleep disturbance reduction (0.07%), and daytime dysfunction reduction (0.19%). Likely mechanisms for the improvement of sleep include autonomic nervous system modulation, muscle tension relief, cortisol regulation, enhanced blood circulation, and psychological benefits such as stress reduction and mood enhancement. CONCLUSION: There is little evidence that stretching exercises positively impact sleep quality in individuals with sleep disorders. Additionally, further research is vital for designing optimal protocols, understanding of the long-term effects, and clarification of the mechanisms.


Asunto(s)
Ejercicios de Estiramiento Muscular , Calidad del Sueño , Trastornos del Sueño-Vigilia , Humanos , Trastornos del Sueño-Vigilia/terapia , Trastornos del Sueño-Vigilia/fisiopatología
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