Biology subjects

Ting, L.

Publications and source records attributed to Ting, L..

6 recordsLinked to original sources

bioRxiv2024

Panax ginseng enhances the effect of metoprolol in chronic heart failure by inhibiting autophagy

ContextPanax ginseng is often used as an adjuvant therapy for heart failure (HF) patients. Metoprolol is widely used in patients with HF. However, there is currently no report on the combined effects of ginseng and metoprolol in patients with HF. ObjectiveThe objective of this study is to investigate the combined effects of ginseng and metoprolol in patients with HF and the exact mechanisms. Materials and methodsA mouse myocardial HF model was used. The serum levels of CK and CK-MB were determined using an automated biochemical analyzer. LDH and cTnT levels were determined using enzyme-linked immunosorbent assays. Autophagy of myocardial cells was evaluated using transmission electron microscopy, and changes in signal pathway proteins related to autophagy were analyzed using Western blot. ResultsThe combination of ginseng and metoprolol can increase the survival rate of HF mice, improve heart function, reduce heart damage, and reduce serum CK, CK-MB, LDH, and cTnT levels. The combination of ginseng and metoprolol reduces autophagy in myocardial cells, reduces the levels of autophagy-related proteins (LC3, p62, Beclin1, and Atg5), and increases the p-PI3K/PI3K, p-Akt/Akt, and p-mTOR/mTOR ratios. Discussion and conclusionGinseng enhances the anti-HF effect of metoprolol. Its mechanism of action may be related to inhibition of autophagy mediated by the PI3K/Akt/mTOR pathway.

pharmacology and toxicology↗

bioRxiv2023

Precise cortical contributions to feedback sensorimotor control during reactive balance

The role of the cortex in shaping automatic whole-body motor behaviors such as walking and balance is poorly understood. Gait and balance are typically mediated through subcortical circuits, with the cortex becoming engaged as needed on an individual basis by task difficulty and complexity. However, we lack a mechanistic understanding of how increased cortical contribution to whole-body movements shapes motor output. Here we use reactive balance recovery as a paradigm to identify relationships between hierarchical control mechanisms and their engagement across balance tasks of increasing difficulty in young adults. We hypothesize that parallel sensorimotor feedback loops engaging subcortical and cortical circuits contribute to balance-correcting muscle activity, and that the involvement of cortical circuits increases with balance challenge. We decomposed balance-correcting muscle activity based on hypothesized subcortically- and cortically-mediated feedback components driven by similar sensory information, but with different loop delays. The initial balance-correcting muscle activity was engaged at all levels of balance difficulty. Its onset latency was consistent with subcortical sensorimotor loops observed in the lower limb. An even later, presumed, cortically-mediated burst of muscle activity became additionally engaged as balance task difficulty increased, at latencies consistent with longer transcortical sensorimotor loops. We further demonstrate that evoked cortical activity in central midline areas measured using electroencephalography (EEG) can be explained by a similar sensory transformation as muscle activity but at a delay consistent with its role in a transcortical loop driving later cortical contributions to balance-correcting muscle activity. These results demonstrate that a neuromechanical model of muscle activity can be used to infer cortical contributions to muscle activity without recording brain activity. Our model may provide a useful framework for evaluating changes in cortical contributions to balance that are associated with falls in older adults and in neurological disorders such as Parkinsons disease.

neuroscience↗

bioRxiv2018

The cost of being stable: Trade-offs between effort and stability across a landscape of redundant motor solutions

Current musculoskeletal modeling approaches cannot account for variability in muscle activation patterns seen across individuals, who may differ in motor experience, motor training, or neurological health. While musculoskeletal simulations typically select muscle activation patterns that minimize muscular effort, and generate unstable limb dynamics, a few studies have shown that maximum-effort solutions can improve limb stability. Although humans and animals likely adopt solutions between these two extremes, we lack principled methods to explore how effort and stability shape how muscle activation patterns differ across individuals. Here we characterized trade-offs between muscular effort and limb stability in selecting muscle activation patterns for an isometric force generation task in a musculoskeletal model of the cat hindlimb. We define effort as the sum of squared activation across all muscles, and limb stability by the maximum real part of the eigenvalues of the linearized musculoskeletal system dynamics, with more negative values being more stable. Surprisingly, stability increased rapidly with only small increases in effort from the minimum-effort solution, suggesting that very small amounts of muscle coactivation are beneficial for postural stability. Further, effort beyond 40% of the maximum possible effort did not confer further increases in stability. We also found multiple muscle activation patterns with equivalent effort and stability, which could underlie variability observed across individuals with similar motor ability. Trade-off between muscle effort and limb stability could underlie diversity in muscle activation patterns observed across individuals, disease, learning, and rehabilitation.\n\nAuthor summaryCurrent computational musculoskeletal models select muscle activation patterns that minimize the amount of muscle activity used to generate a movement, creating unstable limb dynamics. However, experimentally, muscle activation patterns with various level of co-activation are observed for performing the same task both within and across individuals that likely help to stabilize the limb. Here we show that a trade-off between muscular effort and limb stability across the wide range of possible muscle activation patterns for a motor task could explain the diversity of muscle activation patterns seen across individuals, disease, learning and rehabilitation. Increased muscle activity is necessary to stabilize the limb, but could also limit the ability to learn new muscle activation pattern, potentially providing a mechanism to explain individual-specific muscle coordination patterns in health and disease. Finally, we provide a straightforward method for improving the physiological relevance of muscle activation pattern and musculoskeletal stability in simulations.

neuroscience↗

bioRxiv2018

Closed-loop coupling of a muscle to a robotic device for dynamic assessment of muscle function

The contributions of individual muscles to the performance of functional tasks are difficult to evaluate using traditional isolated muscle protocols. During movements, skeletal muscles work against a variety of environmental loads that influence their energetics and function. In turn, these changes in muscle length and muscle velocity alter the forces that the muscle can generate. Classic single-muscle experiments clamp at least one muscle state (length, velocity, force) such that it is independent of the other states, interrupting the dynamic interactions between the muscle and its environment. The purpose of this study was to design and build a real-time feedback system to virtually couple an isolated muscle to a robotic device. Using this approach, the muscle length is not prescribed, but results from the dynamic interactions between the muscle and a physical environment. Therefore our device facilitates the study of how physical interactions between a muscle, limb, and environments alter the force and motion produced by the muscle during controlled muscle activation. To demonstrate the utility of our system, we replicated some salient features of frog swimming, we coupled a frog plantaris longus muscle to a one-degree of freedom \"limb\" that drove a frog foot through water. We demonstrate that under identical muscle stimulation parameters, changes to muscle moment arm, environmental viscosity, and muscle fatigue can significantly alter the resulting muscle force, length, and work.

physiology↗

bioRxiv2018

Interaction of diabetes and smoking on stroke: A population-based cross-sectional survey in China

ObjectivesDiabetes and smoking are known independent risk factors for stroke; however, their interaction concerning stroke is less clear. We aimed to explore such interaction and its influence on stroke in Chinese adults.\n\nDesignCross-sectional study.\n\nSettingCommunity-based investigation in Xuzhou, China.\n\nParticipantsA total of 39,887 Chinese adults who fulfilled the inclusion criteria were included.\n\nMethodsParticipants were selected using a multi-stage stratified cluster method, and completed self-reported questionnaires on stroke and smoking. Type 2 diabetes mellitus (DM2) was assessed by fasting blood glucose or use of antidiabetic medication. Interaction, relative excess risk owing to interaction (RERI), attributable proportion (AP), and synergy index (S) were evaluated using a logistic regression model.\n\nResultsAfter adjustment for age, sex, marital status, educational level, occupation, physical activity, body mass index, hypertension, family history of stroke, alcohol use, and blood lipids, the relationships between DM2 and stroke, and between smoking and stroke, were still significant: odds ratios were 2.75 (95% confidence interval [CI]: 2.03-3.73) and 1.70 (95% CI: 1.38-2.10), respectively. In subjects with DM2 who smoked, the RERI, AP, and S values (and 95% CIs) were 1.80 (1.24-3.83), 0.52 (0.37-0.73), and 1.50 (1.18-1.84), respectively.\n\nConclusionsThe results suggest there are additive interactions between DM2 and smoking and that these affect stroke in Chinese adults.\n\nArticle Summary: Strengths and limitations of this studyO_LIThe strengths of this study were that a large sample population was randomly selected from the general population of Xuzhou and many confounding risk factors were adjusted for.\nC_LIO_LIOwing to the cross-sectional design, we could not determine a causal combined relationship among diabetes, smoking and stroke.\nC_LIO_LIWe were not able to control for some important and well-known risk factors of diabetes, such as heart rate and cardiovascular causes.\nC_LIO_LIWe did not measure fresh fruit consumption, which is causally related to stroke.\nC_LI

epidemiology↗

bioRxiv2017

A Cross-Sectional Study of Set Shifting Impairments and Falling in Individuals with and without Parkinson’s Disease

INTRODUCTION. Individuals with Parkinsons disease (PD) are at increased risk for falls, and exhibit deficits in executive function, including Set Shifting, which can be measured as the difference between parts B and A of the Trailmaking Test. METHODS. We conducted a cross-sectional study using baseline data of PD patients with and without freezing of gait (FOG) (n=69) and community-dwelling neurologically-normal older adults (NON-PD) (n=84) who had volunteered to participate in clinical rehabilitation research. Multivariate logistic regression analyses were performed to determine associations between Set Shifting, PD, and faller status, as determined by [≥]1 self-reported falls in the previous 6 months, after adjusting for demographic and cognitive factors and clinical disease characteristics. RESULTS. Impaired Set Shifting was associated with previous falls after controlling for age, sex, overall cognitive function, PD, FOG, and PD disease duration (OR=1.29 [1.03-1.60]; P=0.02). In models controlling for age, sex, and overall cognitive function, PD was associated with increased fall prevalence among the study sample (OR=4.15 [95% CI 1.65-10.44], P<0.01) and FOG was associated with increased fall prevalence among the PD sample (OR=3.63 [1.22-10.80], P=0.02). Although the strongest associations between Set Shifting and falling were observed among PD without FOG (OR=2.11) compared to HOA (OR=1.14) and PD with FOG (OR=1.46) in a multivariate model that allowed for interaction between set shifting and PD status, there was insufficient evidence to reject the null hypothesis of no interaction. CONCLUSIONS. Set Shifting is associated with previous falls in non-demented older adults with and without PD.\n\nHighlightsO_LIIndividuals with PD are at increased risk for falls, although causes are unclear.\nC_LIO_LIImpaired Set Shifting was associated with falls in older adults with and without PD.\nC_LIO_LIAssociations were strongest among those with PD but without freezing of gait.\nC_LI

neuroscience↗