Balance Control is Sequentially Correlated with Proprioception, Joint Range of Motion, Strength, Pain, and Plantar Tactile Sensation Among Older Adults with Knee Osteoarthritis.

BACKGROUND: Patients with knee osteoarthritis (KOA) are at high risk for falls, which is attributed to their impaired balance control. Identifying factors associated with balance control facilitates the development of precise KOA rehabilitation programs. This study was to investigate the correlations of balance control with proprioception, plantar tactile sensation (PTS), pain, joint range of motion (ROM), and strength among older adults with and without KOA, as well as the magnitudes and sequence of correlation of these factors to balance control. METHODS: A total of 240 older adults with (n = 124, female: 84, age: 68.8 ± 4.0 years) and without (n = 116, female: 64, age: 67.9 ± 3.5 years) KOA were recruited and assigned to the KOA and control groups. Their proprioception, PTS, pain, ROM, and strength were measured. Pearson or Spearman correlations were used to test whether they were significantly related to their Berg Balance Scale (BBS), and factor analysis and multivariate linear regression were used to determine the degrees of correlation between each factor and the BBS. RESULTS: Compared to the control group, the KOA group had lower BBS score, larger proprioception and PTS thresholds, smaller ROM, and less strength (p: 0.008, < 0.001-0.016, < 0.001-0.005, < 0.001-0.014, and < 0.001-0.002, respectively). In the KOA group, the BBS was weakly to moderately correlated with proprioception, PTS, pain, ROM, and strength (r: 0.332-0.501, 0.197-0.291, 0.340, 0.212-0.508, and 0.236-0.336, respectively). While in the control group, the BBS was correlated with proprioception and strength (r: 0.207-0.379, and 0.212-0.410). In the KOA group, BBS = 54.41+ (0.668*strength) - (0.579*PTS) - (1.141*proprioception) + (1.054* ROM) - (0.339*pain). While in the control group, BBS = 53.85+ (0.441*strength) - (0.677*proprioception). CONCLUSION: Worse proprioception and PTS, smaller ROM, and less strength were detected among older adults with KOA, and their proprioception, PTS, pain, ROM, and strength were all related to balance control. Proprioception had the strongest correlations, followed by ROM, strength, pain, and PTS. Precise KOA rehabilitation programs may be proposed following the sequence of improving the five factors.

The proliferation/migration ability mediated by CD151/PI3K/AKT pathway determines the therapeutic effect of hUC-MSCs transplantation on rheumatoid arthritis.

OBJECTIVE: To elucidate the underlying mechanism by which the proliferation and migration abilities of human umbilical cord mesenchymal stem cells (hUC-MSCs) determine their therapeutic efficacy in rheumatoid arthritis treatment. METHODS: The DBA/1J mice were utilized to establish a collagen-induced RA (CIA) mouse model and to validate the therapeutic efficacy of hUC-MSCs transfected with CD151 siRNA. RNA-seq, QT-PCR and western blotting were utilized to evaluate the mRNA and protein levels of the PI3K/AKT pathway, respectively. RESULTS: IFN-γ significantly enhanced the proliferation and migration abilities of hUC-MSCs, up-regulating the expression of CD151, a gene related to cell proliferation and migration. Effective inhibition of this effect was achieved through CD151 siRNA treatment. However, IFN-γ did not affect hUC-MSCs differentiation or changes in cell surface markers. Additionally, transplantation of CD151-interfered hUC-MSCs (siRNA-CD151-hUC-MSCs) resulted in decreased colonization in the toes of CIA mice and worse therapeutic effects compared to empty vector treatment (siRNA-NC-hUC-MSCs). CONCLUSION: IFN-γ facilitates the proliferation and migration of hUC-MSCs through the CD151/PI3K/AKT pathway. The therapeutic efficacy of siRNA-CD151-hUC-MSCs was found to be inferior to that of siRNA-NC-hUC-MSCs.

Can Arthrogenic Muscle Inhibition Exist in Peroneal Muscles Among People with Chronic Ankle Instability? A Cross-sectional Study.

BACKGROUND: Ankle sprains lead to an unexplained reduction of ankle eversion strength, and arthrogenic muscle inhibition (AMI) in peroneal muscles is considered one of the underlying causes. This study aimed to observe the presence of AMI in peroneal muscles among people with chronic ankle instability (CAI). METHODS: Sixty-three people with CAI and another sixty-three without CAI conducted maximal voluntary isometric contraction (MVIC) and superimposed burst (SIB) tests during ankle eversion, then fifteen people with CAI and fifteen without CAI were randomly invited to repeat the same tests to calculate the test-retest reliability. Electrical stimulation was applied to the peroneal muscles while the participants were performing MVIC, and the central activation ratio (CAR) was obtained by dividing MVIC torque by the sum of MVIC and SIB torques, representing the degree of AMI. RESULTS: The intra-class correlation coefficients were 0.77 (0.45-0.92) and 0.92 (0.79-0.97) for the affected and unaffected limbs among people with CAI, and 0.97 (0.91-0.99) and 0.93 (0.82-0.97) for the controlled affected and unaffected limbs among people without CAI; Significant group × limb interaction was detected in the peroneal CAR (p = 0.008). The CARs were lower among people with CAI in the affected and unaffected limbs, compared with those without CAI (affected limb = 82.54 ± 9.46%, controlled affected limb = 94.64 ± 6.37%, p < 0.001; unaffected limb = 89.21 ± 8.04%, controlled unaffected limb = 94.93 ± 6.01%, p = 0.016). The CARs in the affected limbs were lower than those in the unaffected limbs among people with CAI (p = 0.023). No differences between limbs were found for CAR in the people without CAI (p = 0.10). CONCLUSIONS: Bilateral AMI of peroneal muscles is observed among people with CAI. Their affected limbs have higher levels of AMI than the unaffected limbs.

Standard isometric contraction has higher reliability than maximum voluntary isometric contraction for normalizing electromyography during level walking among older adults with knee osteoarthritis.

Introduction: Electromyography (EMG) normalization often relies on maximum voluntary isometric contraction (MVIC), which may not be suitable for knee osteoarthritis (KOA) patients due to difficulties in generating maximum joint torques caused by pain. This study aims to assess the reliability of standard isometric contraction (SIC) for EMG normalization in older adults with KOA, comparing it with MVIC. Methods: We recruited thirty-five older adults with KOA and collected root mean square EMG amplitudes from seven muscles in the affected limb during level walking, SIC, and MVIC tests. EMG data during level walking were normalized using both SIC and MVIC methods. This process was repeated after at least 1 week. We calculated intra-class correlation coefficients (ICCs) with 95% confidence intervals to evaluate between- and within-day reliabilities. Results: SIC tests showed higher between- (ICC: 0.75-0.86) and within-day (ICC: 0.84-0.95) ICCs across all seven muscles compared to MVIC tests. When normalized with SIC, all seven muscles exhibited higher between- (ICC: 0.67-0.85) and within-day (ICC: 0.88-0.99) ICCs compared to MVIC normalization. Conclusion: This study suggests that SIC may offer superior movement consistency and reliability compared to MVIC for EMG normalization during level walking in older adults with KOA.

Deficits in proprioception and strength may contribute to the impaired postural stability among individuals with functional ankle instability.

Purpose: The correlations of postural stability with proprioception and strength may explain the recurrent sprains among individuals with functional ankle instability (FAI). This study aimed to compare anterior-posterior (AP) and medial-lateral (ML) postural stability, along with ankle proprioception and strength between individuals with and without FAI and investigated their correlations. Methods: Forty participants with FAI and another 40 without FAI were recruited. Their postural stability, represented by time to stabilization (TTS) in the AP (TTSAP) and ML (TTSML) directions, was calculated by the ground reaction force during jumping onto a force plate. Their ankle proprioception and strength during plantarflexion/dorsiflexion and inversion/eversion were measured using a proprioception device and a strength testing system, separately. Results: Individuals with FAI had longer TTSAP (p = 0.015) and TTSML (p = 0.006), larger ankle proprioception thresholds (p = 0.000-0.001), and less strength (p = 0.001-0.017) than those without FAI. Correlations between strength and TTSAP were detected among individuals with (ankle plantarflexion, r = -0.409, p = 0.009) and without FAI (ankle plantarflexion, r = -0.348, p = 0.028; ankle dorsiflexion, r = -0.473, p = 0.002). Correlations of proprioception (ankle inversion, r = 0.327, p = 0.040; ankle eversion, r = 0.354, p = 0.025) and strength (ankle eversion, r = -0.479, p = 0.002) with TTSML were detected among individuals without FAI but not among those with FAI. Conclusion: Individuals with FAI have worse postural stability and proprioception and less strength. Their proprioception and strength decreased to a point where they could not provide sufficient functional assistance to the ML postural stability. Improvements in proprioception and strength may be keys to prevent recurrent ankle sprains among individuals with FAI.

Effects of proprioceptive neuromuscular facilitation stretching in relieving pain and balancing knee loading during stepping over obstacles among older adults with knee osteoarthritis: A randomized controlled trial.

OBJECTIVE: The purpose of this study was to investigate the effects of an 8-week proprioceptive neuromuscular facilitation (PNF) stretching in relieving pain and balancing knee loading during stepping over obstacles among older people with knee osteoarthritis, and further explore the improvements in gait patterns. DESIGN: Thirty-two older adults (66~72 years) with KOA were recruited and randomly assigned into PNF or control groups. They received PNF stretching or health lecture series for 8 weeks. Final data analyses were conducted among 13 participants in the PNF and 14 in the control groups. At weeks 0 and 9, they were asked to step over an obstacle of 20% of their leg length. The pain scores and knee abduction moment (KAM) (primary outcomes) were analyzed by multivariate ANOVA, and the gait variables (secondary outcomes) were analyzed by two-way (group by pre-/post) ANOVAs with repeated measures. RESULTS: Significant interactions were detected in the pain score, first and second peaks of KAM, and crossing velocity during stepping over obstacles, and significant between-group differences of these outcomes were detected at week 9. CONCLUSION: An 8-week PNF stretching could relieve pain and balance loading between knee compartments, as well as increase crossing velocity during stepping over obstacles. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR2100042278.

Correction: Glycyrrhizic acid promotes neural repair by directly driving functional remyelination.

Correction for 'Glycyrrhizic acid promotes neural repair by directly driving functional remyelination' by Jing Tian et al., Food Funct., 2020, 11, 992-1005, https://doi.org/10.1039/C9FO01459D.

Proprioceptive Neuromuscular Facilitation Improves Symptoms Among Older Adults With Knee Osteoarthritis During Stair Ascending: A Randomized Controlled Trial.

OBJECTIVE: This study aimed to investigate the effects of a 6-wk proprioceptive neuromuscular facilitation stretching on pain, proprioception, joint range of motion, and joint moments during stair ascending among older adults with knee osteoarthritis. DESIGN: This study is a randomized, controlled, and assessor-blinded trial. Thirty-six older adults with knee osteoarthritis were randomly assigned to the proprioceptive neuromuscular facilitation and the control groups. They received proprioceptive neuromuscular facilitation stretching and health lecture series, respectively, for 6 wks. Final data analysis included 14 participants of the proprioceptive neuromuscular facilitation group and 13 of the control group. Pain score, joint proprioception, range of motion, and joint moments during stair ascending were measured before and after the stretching. Two-way (group by time) analysis of variance with repeated measures was used to evaluate stretching effects. RESULTS: Significant interactions were detected in pain score, joint proprioception, external knee adduction moment, and external knee extension moment. Compared with week 0, the pain score, joint proprioception threshold, and external knee adduction moment decreased, whereas the external knee extension moment increased among older adults in the proprioceptive neuromuscular facilitation group at week 7. CONCLUSIONS: Proprioceptive neuromuscular facilitation could be recommended as one of the clinical treatments for knee osteoarthritis to relieve pain, improve proprioception, and balance load distribution between medial and lateral compartments at the knee.

Urolithin A ameliorates experimental autoimmune encephalomyelitis by targeting aryl hydrocarbon receptor.

BACKGROUND: Urolithin A (URA) is an intestinal microbiota metabolic product from ellagitannin-containing foods with multiple biological activities. However, its role in autoimmune diseases is largely unknown. Here, for first time, we demonstrate the therapeutic effect of URA in an experimental autoimmune encephalomyelitis (EAE) animal model. METHODS: Therapeutic effect was evaluated via an active and passive EAE animal model in vivo. The function of URA on bone marrow-derived dendritic cells (BM-DCs), T cells, and microglia were tested in vitro. FINDINGS: Oral URA (25 mg/kg/d) suppressed disease progression at prevention, induction, and effector phases of preclinical EAE. Histological evaluation showed that significantly fewer inflammatory cells, decreased demyelination, lower numbers of M1-type microglia and activated DCs, as well as reduced infiltrating Th1/Th17 cells were present in the central nervous system (CNS) of the URA-treated group. URA treatment at 25 µM inhibited the activation of BM-DCs in vitro, restrained Th17 cell differentiation in T cell polarization conditions, and in a DC-CD4+ T cell co-culture system. Moreover, we confirmed URA inhibited pathogenicity of Th17 cells in adoptive EAE. Mechanism of URA action was directly targeting Aryl Hydrocarbon Receptor (AhR) and modulating the signaling pathways. INTERPRETATION: Collectively, our study offers new evidence that URA, as a human microbial metabolite, is valuable to use as a prospective therapeutic candidate for autoimmune diseases.

Effects of running biomechanics on the occurrence of iliotibial band syndrome in male runners during an eight-week running programme-a prospective study.

Iliotibial band syndrome (ITBS) is a common injury that is related to running biomechanics. This study aimed to determine the gait characteristics that easily induce ITBS and explore the gait changes after the occurrence of ITBS. Thirty healthy male recreational runners participated in our study. Amongst them, 15 developed ITBS and comprised the ITBS group; the other 15 were healthy and comprised the control group. All participants underwent two gait trials, namely, before the first day of their running and after eight weeks, during which a force platform and a motion capture system collected biomechanical data. After running, the ITBS group exhibited greater anterior pelvic tilt and hip flexion angle than the control group. The ITBS group showed increased trunk inclination angle, whereas the control group demonstrated lower hip flexion, hip adduction angle and hip abductor moment than those at the beginning of running. Decreasing hip flexion, adduction angle and abductor moment may be a reasonable strategy to avoid the occurrence of ITBS. The occurrence of ITBS may be due to the lack of timely gait adjustment. Excessive trunk inclination and anterior pelvic tilt angle may be risks factor in the development of ITBS during running.

Pomegranate peel extract ameliorates the severity of experimental autoimmune encephalomyelitis via modulation of gut microbiota.

Multiple sclerosis (MS) is a CNS autoimmune disease characterized by demyelination and inflammatory infiltration with a high disability rate. Increasing evidence has demonstrated the importance of gut microbiota as an environmental risk factor in MS and its animal model experimental autoimmune encephalomyelitis (EAE). Diet is the main determinant of gut microbiota composition and function, which greatly affects the shaping of microbial structure. Pomegranate peel, a waste product in the production of juice, is rich in health-promoting compounds. However, its individual constituents, immunoregulatory activities, and action associated with bacterial diversity in the gut microbiota are largely unknown. Here, the main nutrient ingredients of pomegranate peel extract (PPE) were identified as phenols, flavonoids, amino acids, carbohydrates, fatty acids, lipids, nucleotides, organic acids, alcohols, and vitamins via metabolomics evaluation. We found, for the first time, oral PPE (100 mg/kg/day) not only effectively relieves EAE, inhibits CNS inflammatory factor infiltration and myelin loss, but also reshapes gut microbiota. Furthermore, recipient EAE mice with fecal transplantation from the PPE-treated donor delayed the disease development significantly. 16S rRNA gene sequencing revealed the increased gut microbiota richness in PPE-treated group. Among them, Lactobacillaceae enriched significantly, while Alcaligenaceae and Acidaminococcacea decreased remarkably. In conclusion, our data demonstrated that gut microbiota mediated the beneficial effects of oral PPE on EAE, and provided new ideas for developing the prebiotic value of pomegranate peel for the treatment of autoimmune diseases.

Eriodictyol suppresses Th17 differentiation and the pathogenesis of experimental autoimmune encephalomyelitis.

T helper 17 (Th17) cells that express interleukin-17 (IL-17) play a key role in various inflammatory diseases, such as multiple sclerosis (MS), and its animal model experimental autoimmune encephalomyelitis (EAE). The retinoic acid receptor-related orphan receptors γt (RORγt) have an indispensable effect on the differentiation of this cell type, and are thus considered a valuable target in the treatment of Th17-related disorders. In this study, we found that eriodictyol (EDT), a natural flavonoid abundant in citrus fruits and peanuts, was located directly in the binding pocket of RORγt, and induced a conformational change that resulted in the effective suppression of the receptor's activity, thus offering insight into the transcriptional inhibition of RORγt-dependent genes. Consistent with this, EDT dose-dependently (5-10 µM) blocked murine Th17 differentiation, and markedly reduced IL-17A secretion in vitro. Furthermore, this compound has been found to have novel properties for directly inhibiting Th1 cell development and promoting Treg cell differentiation at high doses (≥10 µM). EDT administration significantly decreased the clinical severity in the EAE model, with inhibited demyelination and reduced inflammatory responses in the periphery and in the central nervous system (CNS). In the adoptive transfer model, EDT also remarkably suppressed the Th17 cell infiltration and pathogenicity. Collectively, our data demonstrated that EDT, as an agent for the pharmacological inhibition of RORγt, has great potential for immunomodulation, and for use in the treatment of Th17-mediated autoimmune disease.

Proprioceptive neuromuscular facilitation improves pain and descending mechanics among elderly with knee osteoarthritis.

PURPOSE: Knee osteoarthritis (KOA) is a common disease that causes pain and limits functionality in the elderly during daily activities, especially during stair descent. Proprioceptive neuromuscular facilitation (PNF) practices promote multiple-plane joint movements, which relieve pain and increase joint range of motion (ROM). This study aims to examine the effects of a 12-week PNF intervention on pain relief, passive and active joint ROM, external knee adduction moment (KAM), and hip adduction moment (HAM) in the elderly with KOA during stair descent. MATERIALS AND METHODS: Seventy-six elderly who were diagnosed with KOA were assessed for eligibility and, 36 of them met the inclusive criteria, were randomly divided into two groups: the twelve-week PNF intervention group and the control group. Pain score was measured by the Western Ontario and McMaster Universities Arthritis Index (WOMAC). Passive joint ROM was measured using a goniometer. Active joint ROM, KAM, and HAM during stair descent were measured using a motion analysis system with a force platform. All the data were recorded at weeks 0, 6, and 12. RESULTS: Compared to the control group, the PNF group showed a decreased pain score; increased passive hip, knee, and ankle ROM; a decreased minimum knee flexion angle, and increased HAM during stair descent. PERSPECTIVE: Proprioceptive neuromuscular facilitation intervention is a successful method to relieve symptoms of KOA. It relieves pain without increasing KAM, enhances passive ROM, increases active knee flexion ROM, and increases HAM during stair descent in the elderly with KOA.

Glycyrrhizic acid promotes neural repair by directly driving functional remyelination.

Natural compounds are a rich source of effective candidate drugs for the treatment of neurological disorders. Glycyrrhizic acid (GA), the major water-soluble ingredient isolated from Glycyrrhiza glabra, is reported to show anti-inflammatory and immunomodulatory activities. However, its effect on CNS demyelinating disease is unclear. In this study, we showed that GA ameliorated the clinical disease severity of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), especially at the chronic stage of clinical EAE. Histological evaluation demonstrated that, in the prophylactic treatment regimen, GA significantly inhibited inflammatory demyelination in the CNS. During the chronic stage when myelin and axon damage has already occurred, GA induced oligodendrocyte progenitor cell (OPC) differentiation into mature oligodendrocytes, thus effectively accelerating remyelination. Evidence from the cuprizone-induced mouse model of de- and remyelination, ex vivo organotypic slice cultures, and in vitro OPC maturation experiments indicated that the observed efficacy of this compound resulted directly from enhanced remyelination rather than immune suppression. Furthermore, we found that GA promoted oligodendrocyte maturation through modulating GSK-3ß signaling pathways. Our data led to the conclusion that GA could be used as a potential therapeutic candidate for the treatment of demyelinating diseases such as MS, which remains refractory to available treatments.