Search Results (229)

Bone homeostasis relies on the delicate balance between osteoblast-mediated bone formation and osteoclast-mediated bone resorption. The casein kinase 2 interacting protein-1 (CKIP-1), a specific CK2α subunit-interacting protein, has been documented as one of the crucial negative regulators of bone formation. CKIP-1 siRNA therapy has constraints that limit its use in clinical applications. Therefore, it is necessary to explore effective targeting strategies for CKIP-1. In this study, we observed an upregulation of CKIP-1 protein expression in the microgravity environment, while its ubiquitination levels decreased. We further investigated the interaction between CKIP-1 and VHL and found that VHL enhanced CKIP-1 degradation through the ubiquitylation–proteasome system (UPS). Additionally, we discovered a small molecule ligand, named C77, through DNA-encoded library (DEL) screening, which binds to CKIP-1 both in vivo and in vitro, as confirmed by Surface Plasmon Resonance (SPR) and the Cellular Thermal shift assay (CETSA), respectively. Our findings demonstrated the potential of VHL and C77 as guiding factors in the development of CKIP-1-based Proteolysis-Targeting Chimeras (PROTACs), which could be future therapeutic interventions in disuse osteoporosis. Full article

Changes in the structure of bone can occur in space as an adaptive response to microgravity and on Earth due to the adaptive effects to exercise, to the aging of bone cells, or to prolonged disuse. Knowledge of cell-mediated bone remodeling on Earth informs our understanding of bone tissue changes in space and whether these skeletal changes might increase the risk for fractures or premature osteoporosis in astronauts. Comparisons of skeletal health between astronauts and aging humans, however, may be both informative and misleading. Astronauts are screened for a high level of physical fitness and health, are launched with high bone mineral densities, and perform exercise daily in space to combat skeletal atrophy as an adaptive response to reduced weight-bearing function, while the elderly display cellular and tissue pathology as a response to senescence and disuse. Current clinical testing for age-related bone change, applied to astronauts, may not be sufficient for fully understanding risks associated with rare and uniquely induced bone changes. This review aims to (i) highlight cellular analogies between spaceflight-induced and age-related bone loss, which could aid in predicting fractures, (ii) discuss why overreliance on terrestrial clinical approaches may miss potentially irreversible disruptions in trabecular bone microarchitecture induced by spaceflight, and (iii) detail how the cellular effects of the bisphosphonate class of drugs offer a prophylactic countermeasure for suppressing the elevated bone resorption characteristically observed during long-duration spaceflights. Thus the use of the bisphosphonate will help protect the bone from structural changes while in microgravity either along with exercise or alone when exercise is not performed, e.g. after an injury or illness. Full article

The deleterious health effects of prolonged sitting and physical inactivity are well-established, yet these behaviors are pervasive in modern culture. To inform interventions aimed at reducing sedentary behavior and increasing lifestyle activity, this study examined psychological and behavioral economic factors that may be associated with these behaviors. This cross-sectional study was conducted among 4072 adults in Israel. Participants completed a survey pertaining to lifestyle behaviors and economic preferences using an online platform in September 2020. The psychological and behavioral economic factors of interest were patience, self-control, risk-taking, grit, and general self-efficacy. Sedentary behavior and lifestyle activity (e.g., time spent moving about) was assessed using the Rapid Assessment Disuse Index (RADI) tool (higher score indicative of more sitting and less activity). Multivariable linear and logistic regression analyses examined the association between psychological and behavioral economic factors and RADI score. Among 4072 participants, those who were impatient (vs. patient, β: −1.13; 95% CI: −1.89, −0.38) had higher grit (β: −1.25, 95% CI: −1.73, −0.77), and those who were more risk-seeking (β: −0.23; 95% CI: −0.33, −0.13) had lower RADI scores (i.e., less sedentary, more active). Significant associations for grit and risk-taking were also observed when the RADI score was dichotomized, such that individuals who had higher grit or were more risk-seeking were more likely to be non-sedentary/active. No significant associations were observed for self-control or general self-efficacy. Higher grit and more risk-seeking were associated with a decreased propensity for sedentary behaviors and inactivity; these factors may provide targets for interventions aimed at reducing sedentary behavior and increasing lifestyle activity. Full article

Background and Objectives: Bedridden patients are at a high risk of venous thromboembolism (VTE). Passive devices such as elastic compression stockings and intermittent pneumatic compression are common. Leg exercise apparatus (LEX) is an active device designed to prevent VTE by effectively contracting the soleus muscle and is therefore expected to be effective in preventing disuse of the lower limbs. However, few studies have been conducted on the kinematic properties of LEX. Therefore, this study aimed to compare the exercise characteristics of LEX with those of an ergometer, which is commonly used as a lower-limb exercise device, and examine its effect on the two domains of muscle activity and circulatory dynamics. Materials and Methods: This study used a crossover design in which each participant performed both exercises to evaluate the exercise characteristics of each device. Fifteen healthy adults performed exercises with LEX and an ergometer (Terasu Erugo, SDG Co., Ltd., Tokyo, Japan) for 5 min each and rested for 10 min after each exercise. Muscle activity was measured using surface electromyography (Clinical DTS, Noraxon, Scottsdale, AZ, USA), and circulatory dynamics were recorded using a non-invasive impedance cardiac output meter (Physioflow Enduro, Manatec Biomedical, Paris, France). The primary outcome was the mean percentage of maximum voluntary contraction (%MVC) of the soleus muscle during exercise. Results: The mean %MVC of the soleus muscle was significantly higher in the LEX group, whereas no significant differences were observed across the periods and sequences. Heart rate, stroke volume, and cardiac output increased during exercise and decreased thereafter; however, the differences between the devices were not significant. Conclusions: LEX may not only have a higher thromboprophylaxis effect, but also a higher effect on preventing muscle atrophy as a lower-extremity exercise device. Additionally, LEX could potentially be used safely in patients who need to be monitored for changes in circulatory dynamics. Full article

The prevalence of skeletal muscle atrophy, caused by disease and aging, is rising as life expectancy increases. Exercise is the most effective treatment option; however, it is often impractical for individuals suffering from disease or bedridden. The formulation of non-exercise-based interventions is necessary. This study assessed the impact of acupuncture (AC), electro-acupuncture (EA), and electrical stimulation (ES) on muscle mass and contractile properties in a model of casting-induced muscle atrophy. Sprague-Dawley rats (n = 40) were assigned to five groups: control (CON), cast (CT), cast receiving AC (CT-AC), cast receiving EA (CT-EA), and cast receiving ES (CT-ES) (n = 8 each). Treatments were 15 min and three times/week for 14 days. Contractile properties and protein markers of atrophy and inflammation were measured. Casting decreased muscle mass and fiber cross-sectional area, but AC, EA, and ES attenuated cast-induced muscle atrophy. All treatments increased peak twitch tension compared to CT. CT increased the protein levels of MAFbx and MuRF1, while AC, EA, and ES mitigated the elevation of these proteins. Our results indicate that acupuncture, electro-acupuncture, and electrical stimulation show promise as therapeutic strategies to counteract skeletal muscle loss and dysfunction resulting from disuse atrophy caused by injury, disease, and aging. Full article

Italy built its ammasso silo network in the 1930s for two purposes: to stockpile grain and to symbolize fascist power. Much of the network was destroyed in World War II, and over half of the silos still standing are now disused and in disrepair. These structures should be protected and refurbished because they are part of Italy’s historic and agro-industrial heritage and because reusing existing buildings instead of constructing new ones reduces the carbon footprint. To evaluate silo repurposing potential, a method developed for inventorying Spanish silos was adapted and applied to the 30 remaining ammasso silos. The method explores the general features, construction, equipment, and socioeconomic environment of each silo. All extant ammasso silos have machinery for receiving, storing, and dispatching grain, and most have equipment for cleaning, sorting, weighing, and packaging. Vertical-cell silos are challenging to convert, unlike horizontally-oriented silos and other open-plan agro-industrial buildings. Even so, some have already been made over into shops, leisure areas, museums, and even homes. Examples of silo reuse in other countries, such as Spain and Portugal, can offer further useful insights. However, socio-economic indicators suggest that silo repurposing projects are viable only in large population centres. Full article

With an increasing focus on sustainable development and the reuse of disused infrastructure, there is a pressing need for effective decision-making methods. This study explored the use of the PROMETHEE method within a collaborative decision-making framework to assess the adaptive reuse options for a disused railway in Sicily, Italy. Using a participatory paradigm, the research actively involves stakeholders in the assessment process. The collaborative PROMETHEE approach acts as a tool for multi-criteria decision analysis, facilitating the comparison and prioritization of different reuse alternatives based on predefined criteria. The research highlights the effectiveness of PROMETHEE in streamlining decision-making processes for adaptive reuse efforts, particularly in the context of integrated conversions of abandoned railways. By combining multi-criteria decision analysis with collaborative methods, the study contributed to the formulation of sustainable and socially responsible strategies for the valorization of disused railway infrastructure. The results underline the importance of collaborative decision-making processes and the instrumental role of PROMETHEE in assisting stakeholders in evaluating and selecting adaptive reuse options for disused railways, thereby, in turn, promoting the sustainable development of these sites. Full article

Conventional passive ankle foot orthoses (AFOs) have not seen substantial advances or functional improvements for decades, failing to meet the demands of many stakeholders, especially the pediatric population with neurological disorders. Our objective is to develop the first comfortable and unobtrusive powered AFO for children with cerebral palsy (CP), the DE-AFO. CP is the most diagnosed neuromotor disorder in the pediatric population. The standard of care for ankle control dysfunction associated with CP, however, is an unmechanized, bulky, and uncomfortable L-shaped conventional AFO. These passive orthoses constrain the ankle’s motion and often cause muscle disuse atrophy, skin damage, and adverse neural adaptations. While powered orthoses could enhance natural ankle motion, their reliance on bulky, noisy, and rigid actuators like DC motors limits their acceptability. Our innovation, the DE-AFO, emerged from insights gathered during customer discovery interviews with 185 stakeholders within the AFO ecosystem as part of the NSF I-Corps program. The DE-AFO is a biomimetic robot that employs artificial muscles made from an electro-active polymer called dielectric elastomers (DEs) to assist ankle movements in the sagittal planes. It incorporates a gait phase detection controller to synchronize the artificial muscles with natural gait cycles, mimicking the function of natural ankle muscles. This device is the first of its kind to utilize lightweight, compact, soft, and silent artificial muscles that contract longitudinally, addressing traditional actuated AFOs’ limitations by enhancing the orthosis’s natural feel, comfort, and acceptability. In this paper, we outline our design approach and describe the three main components of the DE-AFO: the artificial muscle technology, the finite state machine (the gait phase detection system), and its mechanical structure. To verify the feasibility of our design, we theoretically calculated if DE-AFO can provide the necessary ankle moment assistance for children with CP—aligning with moments observed in typically developing children. To this end, we calculated the ankle moment deficit in a child with CP when compared with the normative moment of seven typically developing children. Our results demonstrated that the DE-AFO can provide meaningful ankle moment assistance, providing up to 69% and 100% of the required assistive force during the pre-swing phase and swing period of gait, respectively. Full article

The decarbonization of the built environment, both in new construction and renovation, is crucial to mitigate its relevant impact on climate change and achieve the Paris Agreement goals. This study presents a systematic LCA-based methodology to assess the whole-life carbon emissions of buildings, applied to a proposal for the regeneration of one of Milan, Italy’s, disused railway yards. As an entry for the 2020 Reinventing Cities competition, Scalo Lambrate is a project for a mainly residential neighborhood with a public park. Strategies to reduce carbon emissions deriving both from the operational energy and construction and maintenance were evaluated and their effects compared to a reference scenario over a time horizon of 100 years. The results show that, while the opportunities to reduce carbon emissions during the use phase are somehow limited due to the already stringent performance requirements for new builds, the use of fast-growing biogenic materials for construction materials, even if mixed with more traditional ones, can provide a significant reduction in the global warming potential over the whole life cycle, with a reduction of 70% compared to the baseline. The remaining emissions can be offset with afforestation initiatives, which, however, must be assessed against land use issues. Full article

Disuse muscle atrophy (DMA) is a significant healthcare challenge characterized by progressive loss of muscle mass and function resulting from prolonged inactivity. The development of effective strategies for muscle recovery is essential. In this study, we established a DMA mouse model through hindlimb suspension to evaluate the therapeutic potential of lactate in alleviating the detrimental effects on the gastrocnemius muscle. Using NMR-based metabolomic analysis, we investigated the metabolic changes in DMA-injured gastrocnemius muscles compared to controls and evaluated the beneficial effects of lactate treatment. Our results show that lactate significantly reduced muscle mass loss and improved muscle function by downregulating Murf1 expression, decreasing protein ubiquitination and hydrolysis, and increasing myosin heavy chain levels. Crucially, lactate corrected perturbations in four key metabolic pathways in the DMA gastrocnemius: the biosynthesis of phenylalanine, tyrosine, and tryptophan; phenylalanine metabolism; histidine metabolism; and arginine and proline metabolism. In addition to phenylalanine-related pathways, lactate also plays a role in regulating branched-chain amino acid metabolism and energy metabolism. Notably, lactate treatment normalized the levels of eight essential metabolites in DMA mice, underscoring its potential as a therapeutic agent against the consequences of prolonged inactivity and muscle wasting. This study not only advances our understanding of the therapeutic benefits of lactate but also provides a foundation for novel treatment approaches aimed at metabolic restoration and muscle recovery in conditions of muscle wasting. Full article

Skeletal muscle unloading occurs during a wide range of conditions, from space flight to bed rest. The unloaded muscle undergoes negative functional changes, which include increased fatigue. The mechanisms of unloading-induced fatigue are far from complete understanding and cannot be explained by muscle atrophy only. In this review, we summarize the data concerning unloading-induced fatigue in different muscles and different unloading models and provide several potential mechanisms of unloading-induced fatigue based on recent experimental data. The unloading-induced changes leading to increased fatigue include both neurobiological and intramuscular processes. The development of intramuscular fatigue seems to be mainly contributed by the transformation of soleus muscle fibers from a fatigue-resistant, “oxidative“ “slow” phenotype to a “fast” “glycolytic“ one. This process includes slow-to-fast fiber-type shift and mitochondrial density decline, as well as the disruption of activating signaling interconnections between slow-type myosin expression and mitochondrial biogenesis. A vast pool of relevant literature suggests that these events are triggered by the inactivation of muscle fibers in the early stages of muscle unloading, leading to the accumulation of high-energy phosphates and calcium ions in the myoplasm, as well as NO decrease. Disturbance of these secondary messengers leads to structural changes in muscles that, in turn, cause increased fatigue. Full article

Post-traumatic osteoporosis (PTO) presents a significant challenge in clinical practice, characterized by demineralization and decreased skeletal integrity following severe traumatic injuries. This literature review manuscript addresses the knowledge gaps surrounding PTO, encompassing its epidemiology, pathophysiology, risk factors, diagnosis, treatment, prognosis, and future directions. This review emphasizes the complexity of the etiology of PTO, highlighting the dysregulation of biomineralization processes, inflammatory cytokine involvement, hormonal imbalances, glucocorticoid effects, vitamin D deficiency, and disuse osteoporosis. Moreover, it underscores the importance of multidisciplinary approaches for risk mitigation and advocates for improved diagnostic strategies to differentiate PTO from other musculoskeletal pathologies. This manuscript discusses various treatment modalities, including pharmacotherapy, dietary management, and physical rehabilitation, while also acknowledging the limited evidence on their long-term effectiveness and outcomes in PTO patients. Future directions in research are outlined, emphasizing the need for a deeper understanding of the molecular mechanisms underlying PTO and the evaluation of treatment strategies’ efficacy. Overall, this review provides a comprehensive overview of PTO and highlights avenues for future investigation to enhance clinical management and patient outcomes. Full article

Disuse muscle atrophy is a disease caused by restricted activity, affecting human health and animal protein quality. While extensive research on its mechanism has been studied in mammals, comparatively little is known about this process in chickens, which are a significant source of protein for human consumption worldwide. Understanding the mechanisms underlying skeletal muscle atrophy in chickens is crucial for improving poultry health and productivity, as well as for developing strategies to mitigate muscle loss. In this study, two groups of chickens were subjected to limb immobilization for two and four weeks, respectively, in order to induce disuse muscle atrophy and uniformly sampled gastrocnemius muscle at the fourth week. A combined analysis of the transcriptome and metabolome was conducted to investigate the mechanisms of disuse-induced muscle atrophy. Through H&E staining and immunofluorescence, we found that, compared to slow-twitch muscle fibers, the fast-twitch muscle fibers showed a greater reduction in cross-sectional area in the immobilized leg, and were also the main driver of changes in cross-sectional area observed in the non-immobilized leg. Integrated analysis revealed that differentially expressed genes (DEGs) and differentially accumulated metabolites (DAMs) were mainly enriched in pathways related to energy metabolism, such as fatty acid metabolism, oxidative phosphorylation (OXPHOS), and glycolysis. These results provide important insights for further research on disuse muscle atrophy. Full article

Introduction: Implant placement in the maxillary anterior area requires sufficient quantity and quality of both soft and hard tissue. In cases where soft and hard tissues are insufficient, additional regeneration using biomaterials is recommended. Treatment using bovine-derived xenograft and acellular dermal matrix (ADM) may increase bone volume and soft tissue thickness. Case and management: A 65-year-old woman sought help for discomfort and aesthetic issues with her denture, reporting missing teeth (11, 12, 13, 14, and 21) and bone volume shrinkage due to disuse atrophy. Intraoral examination revealed 1 mm gingival thickness. CBCT showed labio-palatal bone thickness of 6.0 mm, 5.8 mm, and 4.7 mm for teeth 21, 12 and 14, respectively. Implant planning and surgical guide fabrication were carried out before the surgery. Surgery included the placement of implants 3.3 mm in diameter and 12 mm in length, with the use of xenograft and ADM. Three months post-op, improvements in soft and hard tissues were observed, with a final prosthesis being a long-span implant-supported bridge. Conclusions: Disuse alveolar atrophy causes soft and hard tissue deficiency. The use of xenograft and ADM show favourable results even on a geriatric patient. Full article

Prolonged inactivity and disuse conditions, such as those experienced during spaceflight and prolonged bedrest, are frequently accompanied by detrimental effects on the motor system, including skeletal muscle atrophy and bone loss, which greatly increase the risk of osteoporosis and fractures. Moreover, the decrease in glucose and lipid utilization in skeletal muscles, a consequence of muscle atrophy, also contributes to the development of metabolic syndrome. Clarifying the mechanisms involved in disuse-induced musculoskeletal deterioration is important, providing therapeutic targets and a scientific foundation for the treatment of musculoskeletal disorders under disuse conditions. Skeletal muscle, as a powerful endocrine organ, participates in the regulation of physiological and biochemical functions of local or distal tissues and organs, including itself, in endocrine, autocrine, or paracrine manners. As a motor organ adjacent to muscle, bone tissue exhibits a relative lag in degenerative changes compared to skeletal muscle under disuse conditions. Based on this phenomenon, roles and mechanisms involved in the communication between skeletal muscle and bone, especially from muscle to bone, under disuse conditions have attracted widespread attention. In this review, we summarize the roles and regulatory mechanisms of muscle-derived myokines and extracellular vesicles (EVs) in the occurrence of muscle atrophy and bone loss under disuse conditions, as well as discuss future perspectives based on existing research. Full article