Long non-coding RNA TUG1 is downregulated in Friedreich's ataxia.

Friedreich's ataxia is a neurodegenerative disorder caused by reduced frataxin levels. It leads to motor and sensory impairments and has a median life expectancy of around 35 years. As the most common inherited form of ataxia, Friedreich's ataxia lacks reliable, non-invasive biomarkers, prolonging and inflating the cost of clinical trials. This study proposes TUG1, a long non-coding RNA, as a promising blood-based biomarker for Friedreich's ataxia, which is known to regulate various cellular processes. In a previous study using a frataxin knockdown mouse model, we observed several hallmark Friedreich's ataxia symptoms. Building on this, we hypothesized that a dual-source approach-comparing the data from peripheral blood samples from Friedreich's ataxia patients with tissue samples from affected areas in Friedreich's ataxia knockdown mice, tissues usually unattainable from patients-would effectively identify robust biomarkers. A comprehensive reanalysis was conducted on gene expression data from 183 age- and sex-matched peripheral blood samples of Friedreich's ataxia patients, carriers and controls and 192 tissue data sets from Friedreich's ataxia knockdown mice. Blood and tissue samples underwent RNA isolation and quantitative reverse transcription polymerase chain reaction, and frataxin knockdown was confirmed through enzyme-linked immunosorbent assays. Tug1 RNA interaction was explored via RNA pull-down assays. Validation was performed in serum samples on an independent set of 45 controls and 45 Friedreich's ataxia patients and in blood samples from 66 heterozygous carriers and 72 Friedreich's ataxia patients. Tug1 and Slc40a1 emerged as potential blood-based biomarkers, confirmed in the Friedreich's ataxia knockdown mouse model (one-way ANOVA, P ≤ 0.05). Tug1 was consistently downregulated after Fxn knockdown and correlated strongly with Fxn levels (R 2 = 0.71 during depletion, R 2 = 0.74 during rescue). Slc40a1 showed a similar but tissue-specific pattern. Further validation of Tug1's downstream targets strengthened its biomarker candidacy. In additional human samples, TUG1 levels were significantly downregulated in both whole blood and serum of Friedreich's ataxia patients compared with controls (Wilcoxon signed-rank test, P < 0.05). Regression analyses revealed a negative correlation between TUG1 fold-change and disease onset (P < 0.0037) and positive correlations with disease duration and functional disability stage score (P < 0.04). This suggests that elevated TUG1 levels correlate with earlier onset and more severe cases. This study identifies TUG1 as a potential blood-based biomarker for Friedreich's ataxia, showing consistent expression variance in human and mouse tissues related to disease severity and key Friedreich's ataxia pathways. It correlates with frataxin levels, indicating its promise as an early, non-invasive marker. TUG1 holds potential for Friedreich's ataxia monitoring and therapeutic development, meriting additional research.

The transcript level of long non-coding RNAs; MALAT1 and TUG1, and the association with metabolic syndrome-related parameters in women with overweight and obesity.

Background: Recent studies have addressed the possible role of long non-coding RNAs (lnc-RNAs), Metastasis-Associated Lung Adenocarcinoma Transcript 1 (MALAT1), and Taurine Upregulated Gene 1 (TUG1), in modulating the underlying mechanisms of obesity-related metabolic abnormalities. However, studies are limited and contradictory. Hence, we sought to investigate the relationship of the transcript level of these two lnc-RNAs with metabolic syndrome (MetS)-related parameters in women with obesity and overweight. Method: This cross-sectional study was conducted on 342 women with obese and overweight. We conducted assessments encompassing anthropometric measurements, body composition analysis, fasting blood sugar (FBS) levels, lipid profile analysis, insulin levels, HOMA-IR index, and liver enzyme profiling. A quantitative real-time polymerase chain reaction (PCR) was used to evaluate transcript levels of MALAT1 and TUG1. Also, a 147-question semi-quantitative food frequency questionnaire (FFQ) and the International Physical Activity Questionnaire (IPAQ) were used to evaluate food intake and physical activity, respectively. Results: There was a significant association between FBS and MALAT1 transcript level (ß: 0.382; 95% CI: 0.124, 0.640; P = 0.004). Also, there was a significant association between triglyceride (TG) and MALAT1 transcript level (ß: 4.767; 95% CI: 2.803, 6.731; P < 0.0001). After adjusting for age, BMI, energy intake, and physical activity, an inverse significant association was observed between high-density lipoprotein cholesterol (HDL-c) and MALAT1 transcript level (ß: -0.325; 95% CI: -0.644, -0.006; P = 0.046). Conclusions: Our findings indicated positive associations between mRNA levels of MALAT1 and MetS-related parameters, including FBG, TG, HDL, and systolic blood pressure in overweight and obese women. However, large prospective studies are needed to further establish this concept. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-023-01367-2.

LncRNA taurine upregulated gene 1 in liver disease.

Long non-coding RNAs (lncRNAs) are RNA sequences exceeding 200 nucleotides in length that lack protein-coding capacity and participate in diverse biological processes in the human body, particularly exerting a pivotal role in disease surveillance, diagnosis, and progression. Taurine upregulated gene 1 (TUG1) is a versatile lncRNA, and recent studies have revealed that the aberrant expression or function of TUG1 is intricately linked to the pathogenesis of liver diseases. Consequently, we have summarized the current understanding of the mechanism of TUG1 in liver diseases such as liver fibrosis, fatty liver, cirrhosis, liver injury, hepatitis, and liver cancer. Moreover, mounting evidence suggests that interventions targeting TUG1 or its downstream pathways may hold therapeutic promise for liver diseases. This review elucidates the characteristics, mechanisms, and targets of TUG1 in liver diseases, offering a theoretical basis for the prevention, diagnosis, treatment, and prognostic biomarkers of liver diseases.

LncRNA TUG1 mediates microglial inflammatory activation by regulating glucose metabolic reprogramming.

Microglia are natural immune cells in the central nervous system, and the activation of microglia is accompanied by a reprogramming of glucose metabolism. In our study, we investigated the role of long non-coding RNA taurine-upregulated gene 1 (TUG1) in regulating microglial glucose metabolism reprogramming and activation. BV2 cells were treated with Lipopolysaccharides (LPS)/Interferon-γ (IFN-γ) to establish a microglial activation model. The glycolysis inhibitor 2-Deoxy-D-glucose (2-DG) was used as a control. The expression levels of TUG1 mRNA and proinflammatory cytokines such as Interleukin-1ß (IL-1ß), Interleukin -6, and Tumor Necrosis Factor-α mRNA and anti-inflammatory cytokines such as IL-4, Arginase 1(Arg1), CD206, and Ym1 were detected by RT-qPCR. TUG1 was silenced using TUG1 siRNA and knocked out using CRISPR/Cas9. The mRNA and protein expression levels of key enzymes involved in glucose metabolism, such as Hexokinase2, Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), Lactate dehydrogenase, Glucose 6 phosphate dehydrogenase, and Pyruvate dehydrogenase (PDH), were determined by RT-qPCR and Western blotting. The glycolytic rate of microglial cells was measured using Seahorse. Differential metabolites were determined by metabolomics, and pathway enrichment was performed using these differential metabolites. Our findings revealed that the expression of TUG1 was elevated in proinflammatory-activated microglia and positively correlated with the levels of inflammatory factors. The expression of anti-inflammatory cytokines such as IL-4, Arg1, CD206, and Ym1 were decreased when induced with LPS/IFN-γ. However, this decrease was reversed by the treatment with 2-DG. Silencing of GAPDH led to an increase in the expression of TUG1 and inflammatory factors. TUG1 knockout (TUG1KO) inhibited the expression of glycolytic key enzymes and promoted the expression of oxidative phosphorylation key enzymes, shifting the metabolic profile of activated microglia from glycolysis to oxidative phosphorylation. Additionally, TUG1KO reduced the accumulation of metabolites, facilitating the restoration of the tricarboxylic acid cycle and enhancing oxidative phosphorylation in microglia. Furthermore, the downregulation of TUG1 was found to reduce the expression of both proinflammatory and anti-inflammatory cytokines under normal conditions. Interestingly, when induced with LPS/IFN-γ, TUG1 downregulation showed a potentially beneficial effect on microglia in terms of inflammation. Downregulation of TUG1 expression inhibits glycolysis and facilitates the shift of microglial glucose metabolism from glycolysis to oxidative phosphorylation, promoting their transformation towards an anti-inflammatory phenotype and exerting anti-inflammatory effects in BV2.

Timed up and go demonstrates strong interrater agreement and criterion validity as a functional test in geriatric dogs.

OBJECTIVE: To measure interobserver agreement for 4 functional tasks and their summed geriatric functional score (GFS) and correlate tasks and GFS with client-specific outcome measurements (CSOMs): Canine Brief Pain Inventory (CBPI) pain severity, CBPI pain interference, and Liverpool Osteoarthritis in Dogs. ANIMALS: 89 geriatric dogs were recruited between April and September 2023 from staff, friends, and clients of the Cornell University College of Veterinary Medicine with a median age of 11.0 years and weight of 26.4 kg. METHODS: Dogs underwent 4 sequential functional tests: timed up and go (TUG), cavallettis, figure 8s, and down to stands. Two observers independently scored each dog. The GFS was calculated based on the summed scores of the individual tests. Additional information collected included signalment, weight, measurements reflecting the comorbidities of aging (body condition score and muscle condition score), and CSOMs. RESULTS: Strong interrater agreement was found for all functional tests. The TUG in seconds (sTUG) and figure 8s demonstrated significant (P < .05) moderate to strong correlations to all CSOMs. The GFS showed similar significant correlations with all CSOMs except CBPI pain severity; however, when correlating individual tests to CSOMs, only figure 8s and TUG were significantly contributing to GFS results. Receiver operating characteristic curve analysis defined highly functional dogs as those completing the sTUG in under 3.83 seconds. The sTUG represented the best test for geriatric function given it was objective, reliable, correlated well to CSOMs, and could help identify highly functioning dogs. CLINICAL RELEVANCE: The sTUG appears to be the first practical and reliable functional test of canine geriatric mobility.

LncRNA TUG1 and its Molecular Mechanisms in Human Cancer.

As lncRNAs have increasingly been investigated, they are no longer simply defined as RNAs with no transcription capability. Studies have identified significant associations between the abnormal expression of lncRNAs and human diseases, particularly the mechanisms by which lncRNAs play a part in cancers, which are of considerable attention to researchers. As a result of the complex spatial structure, the mechanisms of interaction of lncRNAs in cancer cells are also complicated and diversified. Among a series of lncRNAs, TUG1, which is now considered to be a very high-value lncRNA, has recently been identified to express abnormally in some malignancies, leading to different alterations in cancer cells proliferation, migration, invasion, apoptosis, and drug resistance, and hence promoting or inhibiting cancer progression. Current studies have implicitly indicated that TUG1 can be used as a therapeutic target for human cancers. However, the biological functions of TUG1 have been studied for a short period of time, and the complete molecular mechanism still needs to be clarified. Accordingly, this review focuses on the principal molecular mechanisms of TUG1 in human cancers and the specific mechanisms of action in different cancer development processes based on existing studies.

lncRNA Biomarkers of Glioblastoma Multiforme.

Long noncoding RNAs (lncRNAs) are RNA molecules of 200 nucleotides or more in length that are not translated into proteins. Their expression is tissue-specific, with the vast majority involved in the regulation of cellular processes and functions. Many human diseases, including cancer, have been shown to be associated with deregulated lncRNAs, rendering them potential therapeutic targets and biomarkers for differential diagnosis. The expression of lncRNAs in the nervous system varies in different cell types, implicated in mechanisms of neurons and glia, with effects on the development and functioning of the brain. Reports have also shown a link between changes in lncRNA molecules and the etiopathogenesis of brain neoplasia, including glioblastoma multiforme (GBM). GBM is an aggressive variant of brain cancer with an unfavourable prognosis and a median survival of 14-16 months. It is considered a brain-specific disease with the highly invasive malignant cells spreading throughout the neural tissue, impeding the complete resection, and leading to post-surgery recurrences, which are the prime cause of mortality. The early diagnosis of GBM could improve the treatment and extend survival, with the lncRNA profiling of biological fluids promising the detection of neoplastic changes at their initial stages and more effective therapeutic interventions. This review presents a systematic overview of GBM-associated deregulation of lncRNAs with a focus on lncRNA fingerprints in patients' blood.

A Step Forward Understanding Directional Limitations in Markerless Smartphone-Based Gait Analysis: A Pilot Study.

The progress in markerless technologies is providing clinicians with tools to shorten the time of assessment rapidly, but raises questions about the potential trade-off in accuracy compared to traditional marker-based systems. This study evaluated the OpenCap system against a traditional marker-based system-Vicon. Our focus was on its performance in capturing walking both toward and away from two iPhone cameras in the same setting, which allowed capturing the Timed Up and Go (TUG) test. The performance of the OpenCap system was compared to that of a standard marker-based system by comparing spatial-temporal and kinematic parameters in 10 participants. The study focused on identifying potential discrepancies in accuracy and comparing results using correlation analysis. Case examples further explored our results. The OpenCap system demonstrated good accuracy in spatial-temporal parameters but faced challenges in accurately capturing kinematic parameters, especially in the walking direction facing away from the cameras. Notably, the two walking directions observed significant differences in pelvic obliquity, hip abduction, and ankle flexion. Our findings suggest areas for improvement in markerless technologies, highlighting their potential in clinical settings.

Long noncoding RNA TUG1 promotes cisplatin resistance in ovarian cancer via upregulation of DNA polymerase eta.

Chemoresistance is a major cause of high mortality and poor survival in patients with ovarian cancer (OVCA). Understanding the mechanisms of chemoresistance is urgently required to develop effective therapeutic approaches to OVCA. Here, we show that expression of the long noncoding RNA, taurine upregulated gene 1 (TUG1), is markedly upregulated in samples from OVCA patients who developed resistance to primary platinum-based therapy. Depletion of TUG1 increased sensitivity to cisplatin in the OVCA cell lines, SKOV3 and KURAMOCHI. Combination therapy of cisplatin with antisense oligonucleotides targeting TUG1 coupled with a drug delivery system effectively relieved the tumor burden in xenograft mouse models. Mechanistically, TUG1 acts as a competing endogenous RNA by downregulating miR-4687-3p and miR-6088, both of which target DNA polymerase eta (POLH), an enzyme required for translesion DNA synthesis. Overexpression of POLH reversed the effect of TUG1 depletion on cisplatin-induced cytotoxicity. Our data suggest that TUG1 upregulation allows OVCA to tolerate DNA damage via upregulation of POLH; this provides a strong rationale for targeting TUG1 to overcome cisplatin resistance in OVCA.

"TiC-TUG": technology in clinical practice using the instrumented timed up and go test-a scoping review.

Digitized assessments have a considerable potential to guide clinicial decision making and monitor progress and disease trajectories. The Timed Up and Go test (TUG) has been long established for assessment in geriatric medicine and instrumented versions (iTUG) have been developed and validated. This scoping review includes studies that applied the iTUG and aims to identify use cases to show where and how iTUG assessment could guide interventions and clinical management. The literature search was limited to peer-reviewed studies that performed pre- and post-intervention measurements with a 3-meter TUG instrumented with body-worn technology in samples of at least 20 subjects aged 60+ years. Of 3018 identified articles 20 were included. Four clinical use cases were identified: stratification for subsequent therapy, monitoring of disease or treatment-associated changes and evaluation of interventions in patients with idiopathic normal pressure hydrocephalus (1), and patients with Parkinson's disease (2); monitoring after joint replacement surgery (3), and evaluation after different exercise and rehabilitation interventions (4). The included studies show diversity in terms of iTUG technology and procedures. The identified use cases highlight clinical relevance and high potential for the clinical application of the iTUG. A consensual approach as well as comprehensive reporting would help to further exploit the potential of the iTUG to support clinical management. Future studies should investigate the benefits of segmental iTUG analysis, responsiveness and participants' perspectives on clinically meaningful changes in iTUG.

Age-specific comparisons in the rate of force development of toe pressure strength and its association with the timed up and go test.

PURPOSE: It has recently been recommended that Rate of Force Development (RFD) be evaluated in addition to maximal muscle strength. There are no studies on RFD of toe pressure strength, and its importance in older adults and the extent to which it is associated with aging needs to be clarified. This study purpose was to examine the association between the RFD of toe pressure strength and timed up and go test (TUG) in an age-specific study. METHODS: This study is a cross-sectional study. Participants in the study included 159 younger adults (26.3 ± 13.1 years, 52% male) and 88 older adults (75.0 ± 6.2 years, 26% male). The RFD of toe pressure strength was determined from the force-time curve obtained during the toe pressure strength assessment, and the ability to exert maximum muscle force in the shortest possible time was assessed. Regression analysis was performed for each group to test the association between RFD of toe pressure strength and TUG by age. RESULTS: Younger adults showed no association between TUG and RFD of toe pressure strength, and significant association between TUG and RFD of toe pressure strength was found only in the older adults (standard regression coefficient = - 0.19, p = 0.048). CONCLUSION: This study showed a significant association between TUG and RFD of toe pressure strength in older adults. These findings show that RFD is one of the functions that should be assessed, particularly in older adults. Furthermore, it was suggested that approaching RFD could improve gait, standing, and sitting movements.

Comparison of the popliteal artery and the capsule of the posterior knee (IPACK) block and the genicular nerve block in primary total knee arthroplasty: A prospective randomized trial.

OBJECTIVES: To compare the efficacy of genicular block and interspace between the popliteal artery and the posterior capsule (IPACK) block in the reduction of postoperative pain, the need for rescue analgesics, and the effects on a range of motion (ROM) in patients with TKA. METHODS: This prospective randomized controlled study was carried out between February and May 2023. Based on the block method, 60 participants were divided into three equal groups. These groups included the IPACK block group (n=20), the genicular block group (n=20), and control group (n=20). Western Ontario and McMaster Universities Arthritis Index (WOMAC), Knee Society score (KSS) and Oxford Knee score (OKS) were used for clinical evaluation in the postoperative period. RESULTS: The KSS and OKS scores of the IPACK and GNB were significantly lower than the control group (p<0.001, p<0.001). The timed up and go (TUG) values of the IPACK and GNB groups at 12th and 24th hour were significantly lower than the control group (p<0.001, p<0.001). The Tramadol rescue values of the IPACK block and control groups were significantly higher than the GNB group (p=0.028, p=0.001, respectively). The ROM values of the IPACK and GNB groups were significantly higher than the control group (p<0.001, p<0.001). CONCLUSION: Both GNB and IPACK blocks had a significant positive impact on postoperative pain scores within the initial 24 hours following total knee arthroplasty (TKA). In comparison with IPACK, GNB had lower opioid consumption in the early postoperative period while also promoting better mobilization.

Aerobic exercise suppresses cognitive injury in patients with Alzheimer's disease by regulating long non-coding RNA TUG1.

BACKGROUND: Alzheimer's disease (AD) is the primary reason for disability of the elderly. This article studied the diagnostic possibility of TUG1 and its potential mechanism in the regulation of aerobic exercise (AE) on AD. METHODS: 77 AD patients undertook a three-month-long cycling exercise, and 77 healthy controls were recruited. Polymerase Chain Reaction amplification was applied to assess the expression of TUG1 and miR-129-5p. The diagnostic possibility was manifested by the receiver operating characteristic (ROC) curve. Spearman correlation analyzed the interrelationships between TUG1 and AD. In vivo, the APP/PS1 double transgenic mouse models of AD were included for rescue experiments. Morris water maze (MWM) was performed to assess cognitive function of AD mice. RESULTS: The content of TUG1 was ascended in AD patients and was diminished after AE. The increase of TUG1 indicated the high risk of the occurrence of AD. TUG1 was closely connected to the cognitive assessment tools of AD patients. The TUG1/ miR-129-5p axis was the regulator of the regulation of AE in AD mice. CONCLUSION: TUG1 was involved in AD development and targeted miR-129-5p to participate in the regulation of AE.

Bodyweight Exercise of Lower and Upper Extremities for Female Patients with Rheumatoid Arthritis and the Timed Up-and-Go Test.

Objectives: At our hospital, orthopedic surgeons and physical and occupational therapists have developed bodyweight exercises for the lower and upper extremities (BELU) for rheumatoid arthritis (RA) patients, including walking [Timed Up-and-Go (TUG) test and figure-of-eight walking) and weight exercises. We aimed to clarify the effect of bodyweight exercise and the Health Assessment Questionnaire (HAQ) cut-off value for a TUG test result of 12 s (or longer) as a risk factor for a fall. Methods: All patients underwent BELU twice weekly at home for 6 weeks. We assessed the HAQ score, TUG time, and the strengths of quadriceps femoris, biceps brachii, handgrip, side pinch, and pulp pinch before and after the intervention. Results: We analyzed the data of 42 participants. The mean age was 67.0 ± 12.1 years. The mean Disease Activity Score-28 for rheumatoid arthritis with erythrocyte sedimentation rate was 2.91 ± 0.91. The mean HAQ score was 0.69 ± 0.62. The dominant quadriceps femoris, biceps brachii, pulp pinch, and side pinch strengths were significantly strengthened. TUG time was improved from 9.0 ± 3.0 s to 8.6 ± 3.2 s (P=0.009). The receiver operating characteristic analysis revealed the cut-off value of HAQ for a TUG time of 12 s (or longer) was 1.0 (AUC 0.903, 95% confidence interval 0.792-1.0). Conclusions: Bodyweight exercises strengthened the muscles in female patients with RA, resulting in improved TUG test results. An indicative HAQ cut-off value of 1.0 (or greater) was identified for a TUG test result of 12 s or longer.

Diabetes and diabetic associative diseases: An overview of epigenetic regulations of TUG1.

The epigenetic regulation of lncRNA TUG1 has garnered significant attention in the context of diabetes and its associated disorders. TUG1's multifaceted roles in gene expression modulation, and cellular differentiation, and it plays a major role in the growth of diabetes and the issues that are related to it due to pathological processes. In diabetes, aberrant epigenetic modifications can lead to dysregulation of TUG1 expression, contributing to disrupted insulin signaling, impaired glucose metabolism, and beta-cell dysfunction. Moreover, it has been reported that TUG1 contributes to the development of problems linked to diabetes, such as nephropathy, retinopathy, and cardiovascular complications, through epigenetically mediated mechanisms. Understanding the epigenetic regulations of TUG1 offers novel insights into the primary molecular mechanisms of diabetes and provides a possible path for healing interventions. Targeting epigenetic modifications associated with TUG1 holds promise for restoring proper gene expression patterns, ameliorating insulin sensitivity, and mitigating the inception and development of diabetic associative diseases. This review highlights the intricate epigenetic landscape that governs TUG1 expression in diabetes, encompassing DNA methylation and alterations in histone structure, as well as microRNA interactions.

Fall Risk Assessment in Stroke Survivors: A Machine Learning Model Using Detailed Motion Data from Common Clinical Tests and Motor-Cognitive Dual-Tasking.

BACKGROUND: Falls are common and dangerous for stroke survivors. Current fall risk assessment methods rely on subjective scales. Objective sensor-based methods could improve prediction accuracy. OBJECTIVE: Develop machine learning models using inertial sensors to objectively classify fall risk in stroke survivors. Determine optimal sensor configurations and clinical test protocols. METHODS: 21 stroke survivors performed balance, Timed Up and Go, 10 Meter Walk, and Sit-to-Stand tests with and without dual-tasking. A total of 8 motion sensors captured lower limb and trunk kinematics, and 92 spatiotemporal gait and clinical features were extracted. Supervised models-Support Vector Machine, Logistic Regression, and Random Forest-were implemented to classify high vs. low fall risk. Sensor setups and test combinations were evaluated. RESULTS: The Random Forest model achieved 91% accuracy using dual-task balance sway and Timed Up and Go walk time features. Single thorax sensor models performed similarly to multi-sensor models. Balance and Timed Up and Go best-predicted fall risk. CONCLUSION: Machine learning models using minimal inertial sensors during clinical assessments can accurately quantify fall risk in stroke survivors. Single thorax sensor setups are effective. Findings demonstrate a feasible objective fall screening approach to assist rehabilitation.

Compositional associations between movement-related behaviours and functional outcomes post-stroke.

PURPOSE: To examine the associations between the composition of movement-related behaviours (sedentary behaviour, sleep, standing, and stepping) and functional outcomes post-stroke. METHODS: This study included 34 adults with stroke (mean age: 64.6 ± 12.5 years; time since stroke: 3.5 ± 1.1 months) who underwent an 8-week sedentary behaviour intervention. Functional outcomes were assessed using the timed up and go (TUG) and gait speed tests. Compositional data analysis was used to investigate the relationships between movement-related behaviours and functional outcomes. RESULTS: The baseline composition of movement-related behaviours showed significant associations with changes in TUG (F = 4.28, p = 0.01) and gait speed (F = 4.63, p = 0.01) after the 8-week reducing sedentary behaviour intervention. Reallocating ≥ 30 min/day to stepping, while proportionally decreasing other movement-related behaviours, was associated with a significant change in TUG. Similarly, a relative reallocation of ≥ 40 min/day to stepping was associated with a clinically meaningful change in gait speed. CONCLUSIONS: This study highlights the importance of considering movement-related behaviours in relation to functional outcomes post-stroke. Reallocating at least 30 min per day to stepping, relative to a reduction in other movement-related behaviours, is associated with significant and meaningful change in functional outcomes.

Reallocating at least 30 minutes/day to stepping, relative to a decrease in other movement-related behaviours, is associated with a positive change in functional mobility after an 8-week post-stroke sedentary behaviour intervention.Relative to a decrease in other movement-behaviours, reallocating ≥ 40 minutes/day to stepping is associated with a meaningful change in gait speed.Reallocating time to standing or sleep at the expense of other movement behaviours is not associated with better functional mobility or gait speed.Finding the optimal balance in movement-related behaviours that favours more stepping may lead to improvements in both functional mobility and gait speed.

Establishing Normative Values for Performance-Based Tests in Older Thai Adults: A Nationwide Cross-Sectional Study.

OBJECTIVE: To determine normative values and identify contributing factors for physical performance tests in older, Thai, community-dwelling adults. DESIGN: Nationwide cross-sectional study. SETTING: Thai older community-dwelling adults. PARTICIPANTS: Thai older community-dwelling adults aged ≥60 years who had no major health problems (N=1430) between March 2021 and August 2022. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Normative values for the timed Up and Go (TUG) test, gait speed test, and 5-times sit-to-stand (5TSTS) test were determined for sex and age groups. Multivariable quantile regression analysis was employed to evaluate the participants, considering factors that may influence physical performance, such as height, and Charlson comorbidity index (CCI). RESULTS: The study included 1430 eligible participants. Their mean age was 68.4±5.8 years, and 58.5% were women. Men demonstrated superior physical performance in the medians (p50) of the TUG (10.0 s vs 11.0 s), gait speed (0.98 m/s vs 0.91 m/s), and 5TSTS (14.0 s vs 16.1 s) tests compared with women. These differences were consistently observed across age groups. Moreover, age, sex, and height were significantly associated with poor physical performance. CONCLUSION: This study observed variations in the normative values of TUG, gait speed, and 5TSTS tests among different age groups of older, Thai, community-dwelling adults. Additionally, our findings identified age, sex, and height as significant contributing factors to physical performance in this population.

Use of the improved tug-of-war acupuncture for promoting cartilage repair by inducing macrophage polarization in knee osteoarthritis.

Introduction: Knee osteoarthritis (KOA) is a type of joint disease causing degenerative changes that are challenging to treat. The improved tug-of-war acupuncture (BHZF) can improve joint pain in KOA. However, the associated mechanism has not been validated. Methods: The KOA rabbit model was established. After the surgery, the improved BHZF was provided as an intervention, and the animals were euthanized after 2 weeks. Histopathological changes in the synovium and cartilage were observed on hematoxylin & eosin staining and Safranin O-Fast Green staining. Synovial fluid and serum samples were collected to assess the presence of cytokines using the enzyme-linked immunosorbent assay. The expression of M1 macrophage (CD86) and M2 macrophage (ARG1) markers in the cartilage and synovium was detected via immunohistochemistry and immunofluorescence assays. Results: The improved BHZF could reduce KOA-related pain and inhibit joint swelling. Further, it significantly maintained the morphology of articular chondrocytes in KOA and reduced the decomposition of the cartilage matrix. Then, it significantly reduced the expression of CD86-positive cells (P < 0.05), and increased the expression of ARG1-positive cells in the cartilage and synovium (P < 0.05). Moreover, it significantly decreased the expression of inflammatory factors interleukin (IL)-1 beta and tumor necrosis factor-alpha in the serum and synovial fluid (P < 0.05), and significantly increased the expression levels of anti-inflammatory cytokines IL-4 and IL-10 (P < 0.05). Conclusions: The improved BHZF can relieve pain and improve cartilage damage by regulating macrophage polarization in KOA.

Klotho-derived peptide 1 inhibits cellular senescence in the fibrotic kidney by restoring Klotho expression via posttranscriptional regulation.

Background: Klotho deficiency is a common feature of premature aging and chronic kidney disease (CKD). As such, restoring Klotho expression could be a logic strategy for protecting against various nephropathies. In this study, we demonstrate that KP1, a Klotho-derived peptide, inhibits cellular senescence by restoring endogenous Klotho expression. Methods: The effects of KP1 on cellular senescence and Klotho expression were assessed in mouse models of CKD. RNA-sequencing was employed to identify the microRNA involved in regulating Klotho by KP1. Gain- or loss-of-function approaches were used to assess the role of miR-223-3p and IncRNA-TUG1 in regulating Klotho and cellular senescence. Results: KP1 inhibited senescence markers p21, p16 and γ-H2AX in tubular epithelial cells of diseased kidneys, which was associated with its restoration of Klotho expression at the posttranscriptional level. Profiling of kidney microRNAs by RNA sequencing identified miR-223-3p that bound to Klotho mRNA and inhibited its protein expression. Overexpression of miR-223-3p inhibited Klotho and induced p21, p16 and γ-H2AX, which were negated by KP1. Conversely, inhibition of miR-223-3p restored Klotho expression, inhibited cellular senescence. Furthermore, miR-223-3p interacted with lncRNA-TUG1 and inhibited its expression. Knockdown of lncRNA-TUG1 increased miR-223-3p, aggravated Klotho loss and worsened cellular senescence, whereas KP1 mitigated all these changes. Conclusion: These studies demonstrate that KP1 inhibits cellular senescence and induces Klotho expression via posttranscriptional regulation mediated by miR-223-3p and lncRNA-TUG1. By restoring endogenous Klotho, KP1 elicits a broad spectrum of protective actions and could serve as a promising therapeutic agent for fibrotic kidney disorders.