Effect of lace-up ankle brace on the tibiotalar and subtalar joint during the landing.

Objective: Ankle braces can affect the kinematics of the ankle joint during landing tasks. Previous studies were primarily relied on traditional marker-based motion capture systems, which pose limitations in non-invasively capturing the motion of the talus bone. The effect of ankle braces on the in vivo kinematics of the tibiotalar and subtalar joints during landing remains unknown. This study used a high-speed dual fluoroscopic imaging system (DFIS) and magnetic resonance imaging (MRI) to investigate effect of ankle braces on the in vivo kinematics of the tibiotalar and subtalar joints during landing. Methods: Fourteen healthy participants were recruited for this study. During the experiment, static three-dimensional MRI data were collected for each participant, and 3D ankle joint models for the calcaneus, talus, and tibia were constructed. The DFIS was used to capture the images of each participant performing a single-leg landing-jump task at a height of 40 cm. The images were captured once with and without a brace in the fatigue condition, which was induced by running. The six-degree-of-freedom (6DOF) kinematic data were obtained by 2D-3D registration. Results: The flexion-extension range of motion (ROM) (42.73 ± 4.76° vs. 38.74 ± 5.43°, p = 0.049) and anterior-posterior translation ROM (16.86 ± 1.74 mm vs. 15.03 ± 1.73 mm, p = 0.009) of the tibiotalar joint were decreased. The maximum inversion angle (-3.71 ± 2.25° vs. 2.11 ± 1.83°, p = 0.047) of the subtalar joint was decreased. Conclusion: The ankle brace limited the flexion-extension ROM of the tibiotalar joints and the inversion angle of the subtalar joint during landing.

Effects of fatigue on the in vivo kinematics and kinetics of talocrural and subtalar joint during landing.

Objective: Fatigue can affect the ankle kinematic characteristics of landing movements. Traditional marker-based motion capture techniques have difficulty in accurately obtaining the kinematics of the talocrural and subtalar joints. This study aimed to investigate the effects of fatigue on the talocrural and subtalar joints during the landing using dual fluoroscopic imaging system (DFIS). Methods: This study included fourteen healthy participants. The foot of each participant was scanned using magnetic resonance imaging to create 3D models. High-speed DFIS was used to capture images of the ankle joint during participants performing a single-leg landing jump from a height of 40 cm. Fatigue was induced by running and fluoroscopic images were captured before and after fatigue. Kinematic data were obtained by 3D/2D registration in virtual environment software. The joint kinematics in six degrees of freedom and range of motion (ROM) were compared between the unfatigued and fatigued conditions. Results: During landing, after the initial contact with the ground, the main movement of the talocrural joint is extension and abduction, while the subtalar joint mainly performs extension, eversion, and abduction. Compared to unfatigued, during fatigue the maximum medial translation (1.35 ± 0.45 mm vs. 1.86 ± 0.69 mm, p = 0.032) and medial-lateral ROM (3.19 ± 0.60 mm vs. 3.89 ± 0.96 mm, p = 0.029) of the talocrural joint significantly increased, the maximum flexion angle (0.83 ± 1.24° vs. 2.11 ± 1.80°, p = 0.037) of the subtalar joint significantly increased, and the flexion-extension ROM (6.17 ± 2.21° vs. 7.97 ± 2.52°, p = 0.043) of the subtalar joint significantly increased. Conclusion: This study contributes to the quantitative understanding of the normal function of the talocrural and subtalar joints during high-demand activities. During landing, the main movement of the talocrural joint is extension and abduction, while the subtalar joint mainly performs extension, eversion, and abduction. Under fatigue conditions, the partial ROM of the talocrural and subtalar joints increases.

Sex differences in peripheral monoamine transmitter and related hormone levels in chronic stress mice with a depression-like phenotype.

Backgrounds: Chronic stress could induce depression-like phenotype in animal models. Previous data showed that sex differences exist after chronic stress model establishment, however, the detailed information about the difference of blood biochemical indexes is not clear. In this study, we aim to supply comparison of monoamine transmitters and related hormone markers in serum between male and female depressed mice, and in order to better understand the sex difference in transmitters and hormone levels in depression occurrence and development. Methods: Sixty C57BL/6 mice (both male and female) were divided into two groups by gender. Same gender mice were then divided randomly into the non-treated control group and chronic stress group which was exposed to 8 weeks of chronic unpredictable mild stress (CUMS). Depression-like behavior was assessed with open-field test and sucrose preference test. Blood sample was collected and monoamine transmitter and related hormone in serum were measured by ELISA. Results: The depression-like phenotype mice model was established successfully after 8 weeks of chronic stress. The locomotion activity scores in male stressed mice declined more than that in female stressed mice, while the exploratory behavior scores in female stressed mice declined more than that in male stressed mice. Compared to non-treated control group mice, mice in the chronic stress group in response to stress showed greater declines in monoamine transmitters (5-HT, dopamine, norepinephrine) and sex hormones (androgen, estrogen, oxytocin and prolactin), while stress hormones (adrenaline, corticosterone and ACTH) were significantly increased. The decrease of norepinephrine, androgen and estrogen in female stressed mice was greater than in male stressed mice, whereas the 5-HT and oxytocin in male stressed mice decreased more than in female stressed mice, and the corticosterone in male stressed mice increased more than in female stressed mice. Conclusion: Sex differences of monoamine transmitter and related hormone levels in serum occurred in chronic stress induced depression-like phenotype mice model. It may provide a useful reference to guide precise antidepressant treatment in different gender population in clinical care.

Antitumor Effect of Fluoxetine on Chronic Stress-Promoted Lung Cancer Growth via Suppressing Kynurenine Pathway and Enhancing Cellular Immunity.

Background: Chronic stress promotes cancer growth. Antidepressant fluoxetine (FLX) is usually prescribed for cancer patients with comorbid depression. FLX displays inhibition on cancer cell proliferation, however, the in vivo activity has not been investigated. Methods: We explored the antitumor effect of FLX in subcutaneous transplanted lung cancer cells in a tumor-bearing mouse model. Fifty-six C57BL/6 mice were randomly divided into group A (blank control), group B (tumor-bearing control), group C (tumor-bearing + FLX), group D (CUMS control), group E (CUMS + FLX), group F (tumor-bearing + CUMS), and group G (tumor-bearing + CUMS + FLX). 5-HT, tryptophane (Trp), kynurenine, IFN-γ, TNF-α, IL-1α, IL-1ß, IL-2, IL-4, IL-6, IL-10, IL-17A levels were measured by ELISA. T helper (Th), cytotoxic T (Tc) and regulatory T cells (Tregs) subtype were measured by flow cytometry. The antitumor effects of FLX were evaluated by tumor weight. The expression of kynurenine pathway related genes TDO, IDO1, IDO2, and apoptosis-related genes caspase1, 3, 4, 5, 7, 12 in tumor tissues were measured by western blotting and qRT-PCR. A549 cells were exposed with FLX (15 µmol/L) and its effect on cell proliferation, migration, and clonal formation were detected. Kynurenine pathway and apoptosis related gene expression were also measured. Results: In vivo, chronic stress promoted tumor growth in C57BL/6 mice. FLX administration not only significantly reversed chronic unpredictable mild stress (CUMS)-induced reduction of 5-HT and Trp, increment of kynurenine, but increased CD4+ Th and CD8+ Tc cells, and reduced CD25+ FOXP3+ Tregs. FLX promoted Th to differentiate into Th1 cells and increased IL-2 and IFN-γ, meanwhile inhibited Th differentiate into Th2 and Th17 cells and decreased the concentrations of IL-4, IL-6, IL-10, and IL-17A. Chronic stress obviously up-regulated IDO1 and IDO2 expression, down-regulated caspase 4, 7, and 12 expression, meanwhile FLX administration reversed this regulation. However, there was no significant change in TDO, caspase 1, 3, 5. Similarly, in vitro, FLX administration significantly inhibited the proliferation, migration, and clonal formation of A549 cells and induced cell apoptosis. FLX administration down-regulated the expression of IDO1, IDO2, and up-regulated caspase 4, 5, and 7. Conclusion: Fluoxetine administration could inhibit tumor growth. The inhibition might be via suppressing kynurenine pathway and enhancing cellular immunity.

Chronic Stress Disturbs Metabolome of Blood Plasma and Urine in Diabetic Rats.

About 30% of diabetes patients suffer from varying degrees of depression. Diabetes itself is associated with abnormal carbohydrate and energy metabolism. Whether chronic stress-induced depression-like behavior impacts the metabolome of blood plasma and urine in diabetes is not clear. This study aimed to investigate the effect of chronic stress on metabolome of plasma and urine in spontaneously diabetic Goto-Kakizaki (GK) rats. The GK rats were subjected to 8 weeks' chronic unpredictable mild stress (CUMS) to induce depression-like behavior. Metabolome analysis of blood plasma and urine using liquid chromatography mass spectrometry (LC/MS) was performed. Multivariate data analysis was used to evaluate the data. Behavior and biochemical assay confirmed the successful establishment of CUMS-induced depression-like behavior model in rats. Disturbance of 20 plasma metabolites and 16 urine metabolites were altered in CUMS-induced depression GK rats as compared to control ones. These disturbed metabolites were involved in fatty acid metabolism, sphingolipid metabolism, phenylalanine metabolism, citrate cycle, glycolysis, glutathione metabolism, and nicotinate and nicotinamide metabolism. This study suggest that chronic stress-induced depression-like behavior may further disturb diabetes-itself energy metabolome. The plasma and urine lipid metabolites monitoring may be useful for early detection of depression in patients with diabetes mellitus.