A below-knee compression garment reduces fatigue-induced strength loss but not knee joint position sense errors.

PURPOSE: We examined the possibility that wearing a below-knee compression garment (CG) reduces fatigue-induced strength loss and joint position sense (JPS) errors in healthy adults. METHODS: Subjects (n = 24, age = 25.5 ± 4 years) were allocated to either one of the treatment groups that performed 100 maximal isokinetic eccentric contractions at 30°-1 with the right-dominant knee extensors: (1) with (EXPCG) or (2) without CG (EXP) or to (3) a control group (CONCG: CG, no exercise). Changes in JPS errors, and maximal voluntary isometric contraction (MVIC) torque were measured immediately post-, 24 h post-, and 1 week post-intervention in each leg. All testing was done without the CG. RESULTS: CG afforded no protection against JPS errors. Mixed analysis of variance (ANOVA) revealed that absolute JPS errors increased post-intervention in EXPCG and EXP not only in the right-exercised (52%, p = 0.013; 57%, p = 0.007, respectively) but also in the left non-exercised (55%, p = 0.001; 58%, p = 0.040, respectively) leg. Subjects tended to underestimate the target position more in the flexed vs. extended knee positions (75-61°: - 4.6 ± 3.6°, 60-50°: - 4.2 ± 4.3°, 50-25°: - 2.9 ± 4.2°), irrespective of group and time. Moreover, MVIC decreased in EXP but not in EXPCG and CONCG at immediately post-intervention (p = 0.026, d = 0.52) and 24 h post-intervention (p = 0.013, d = 0.45) compared to baseline. CONCLUSION: Altogether, a below-knee CG reduced fatigue-induced strength loss at 80° knee joint position but not JPS errors in healthy younger adults.

Melatonin alleviates intestinal injury, neuroinflammation and cognitive dysfunction caused by intestinal ischemia/reperfusion.

Intestinal ischemia/reperfusion (I/R) can cause multiple organ damage with extremely high morbidity and mortality. Melatonin has anti-inflammatory, anti-oxidative and anti-apoptotic effects against various diseases. This study aimed to explore whether melatonin had a protective effect against intestinal I/R-induced neuroinflammation and cognitive dysfunction, and investigate its potential mechanisms. In this study, melatonin was administered to the rats with intestinal I/R, then histological changes in intestine and brain (frontal cortex and hippocampal CA1 area) tissues and cognitive function were detected, respectively. The encephaledema and blood-brain barrier (BBB) permeability were observed. Moreover, the alterations of proinflammatory factors (tumor necrosis factor-α, interleukin-6 and interleukin-1ß), oxidative response (malondialdehyde, superoxide dismutase, and reactive oxygen species), apoptosis and proteins associated with inflammation,including Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (Myd88) and phosphorylated nuclear factor kappa beta (NF-κB), and apoptosis (cleaved caspase-3) in brain tissues were examined. Furthermore, the expressions of TLR4, Myd88, and microglial activity were observed by multiple immunofluorescence staining. The results showed that intestinal I/R-induced abnormal neurobehavior and cerebral damage were ameliorated after melatonin treatment, which were demonstrated by improved cognitive dysfunction and aggravated histology. Furthermore, melatonin decreased the levels of proinflammatory factors and oxidative stress in plasma, intestine and brain tissues, attenuated apoptotic cell, and inhibited the expressions of related proteins and the immunoreactivity of TLR4 or Myd88 in microglia in brain tissues. These findings showed that melatonin might relieve neuroinflammation and cognitive dysfunction caused by intestinal I/R, which could be, at least partially, related to the inhibition of the TLR4/Myd88 signaling in microglia.

BNIP3L-Dependent Mitophagy Promotes HBx-Induced Cancer Stemness of Hepatocellular Carcinoma Cells via Glycolysis Metabolism Reprogramming.

Hepatitis B virus (HBV) is one of predisposing factors for hepatocellular carcinoma (HCC). The role of HBV x protein (HBx) in mediating the induction and maintenance of cancer stemness during HBV-related HCC attracts considerable attention, but the exact mechanism has not been clearly elucidated. Here, ABCG2-dependent stem-like side population cells, which are thought to be liver cancer stem cells (LCSCs), were present in HCC cells, and the fraction of this subset was increased in HBx-expressing HCC cells. In addition, glycolysis was upregulated in LCSCs and HBx-expressing HCC cells, and intervention of glycolysis attenuated cancer stem-like phenotypes. Mitochondria play an important role in the maintenance of energy homeostasis, BNIP3L-dependent mitophagy was also activated in LCSCs and HBx-expressing HCC cells, which triggered a metabolic shift toward glycolysis. In summary, we proposed a positive feedback loop, in which HBx induced BNIP3L-dependent mitophagy which upregulated glycolytic metabolism, increasing cancer stemness of HCC cells in vivo and in vitro. BNIP3L might be a potential therapeutic target for intervention of LCSCs-associated HCC. Anti-HBx, a monoclonal antibody targeting intracellular HBx, had the potential to delay the progression of HBV infection related-HCC.

Cyclooxygenase-2 modulates ER-mitochondria crosstalk to mediate superparamagnetic iron oxide nanoparticles induced hepatotoxicity: an in vitro and in vivo study.

Mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs) are central microdomains of the ER that interact with mitochondria. MAMs provide an essential platform for crosstalk between the ER and mitochondria and play a critical role in the local transfer of calcium (Ca2+) to maintain cellular functions. Despite the potential uses of superparamagnetic iron oxide nanoparticles (SPIO-NPs) in biomedical applications, the hepatotoxicity of these nanoparticles (NPs) is not well characterized and little is known about the involvement of MAMs in ER-mitochondria crosstalk. We studied SPIO-NPs-associated hepatotoxicity in vitro and in vivo. In vitro, human normal hepatic L02 cells were exposed to SPIO-NPs (2.5, 7.5, and 12.5 µg/mL) for 6 h and SPIO-NPs (12.5 µg/mL) was found to induce apoptosis. In vivo, SPIO-NPs induced liver injury when mice were intravenously injected with 20 mg/kg body weight SPIO-NPs for 24 h. Based on both in vitro and in vivo studies, we found that the structure and Ca2+ transport function of MAMs were perturbated and an accumulation of cyclooxygenase-2 (COX-2) in MAMs fractions was increased upon treatment of SPIO-NPs. The interaction between COX-2 and the components of MAMs, in terms of IP3R-GRP75-VDAC1 complex, was also revealed. Furthermore, the role of COX-2 in SPIO-NPs-associated hepatotoxicity was investigated by modifying the expression of COX-2. We demonstrated that COX-2 increases the structural and functional ER-mitochondria coupling and enhances the efficacy of ER-mitochondria Ca2+ transfer through the MAMs, thus sensitizing hepatocytes to a mitochondrial Ca2+ overload-dependent apoptosis. Taken together, our findings link SPIO-NPs-triggered hepatotoxicity with ER-mitochondria Ca2+ crosstalk which is mediated by COX-2 and provide mechanistic insight into the impact of interorganelle ER-mitochondria communication on hepatic nanotoxicity.

Aflatoxin B1 enhances pyroptosis of hepatocytes and activation of Kupffer cells to promote liver inflammatory injury via dephosphorylation of cyclooxygenase-2: an in vitro, ex vivo and in vivo study.

Aflatoxin B1 (AFB1), a food contaminant derived from Aspergillus fungi, has been reported to cause hepatic immunotoxicity via inflammatory infiltration and cytokines release. As a pro-inflammatory factor, cyclooxygenase-2 (COX-2) is widely involved in liver inflammation induced by xenobiotics. However, the mechanism by which AFB1-induced COX-2 regulates liver inflammatory injury via hepatocytes-Kupffer cells (KCs) crosstalk remains unclear and requires further elucidation. Here, we established a COX-2 upregulated model with AFB1 treatment in vivo (C57BL/6 mice, 1 mg/kg body weight, i.g, 4 weeks) and in vitro (human liver HepaRG cells, 1 µM for 24 h). In vivo, AFB1-treated mice exhibited NLRP3 inflammasome activation, inflammatory infiltration, and increased recruitment of KCs. In vitro, dephosphorylated COX-2 by protein phosphatase 2A (PP2A)-B55δ promoted NLRP3 inflammasome activation, including mitochondrial translocation of NLRP3, caspase 1 cleavage, and IL-1ß release. Moreover, phosphorylated COX-2 at serine 601 (p-COX-2Ser601) underwent endoplasmic reticulum (ER) retention for proteasome degradation. Furthermore, pyroptosis and inflammatory response induced by AFB1 were relieved with COX-2 genetic (siPTGS2) intervention or pharmaceutic (celecoxib, 30 mg/kg body weight, i.g, 4 weeks) inhibition of COX-2 via NLRP3 inflammasome suppression in vivo and in vitro. Ex vivo, in a co-culture system with murine primary hepatocytes and KCs, activated KCs induced by damaged signals from pyroptotic hepatocytes, formed a feedback loop to amplify NLRP3-dependent pyroptosis of hepatocytes via pro-inflammatory signaling, leading to liver inflammatory injury. Taken together, our data suggest a novel mechanism that protein quality control of COX-2 determines the intracellular distribution and activation of NLRP3 inflammasome, which promotes liver inflammatory injury via hepatocytes-KCs crosstalk.

Position of compression garment around the knee affects healthy adults' knee joint position sense acuity.

Athletes use compression garments (CGs) to improve sport performance, accelerate rehabilitation from knee injuries or to enhance joint position sense (JPS). The position of CGs around the knee may affect knee JPS but the data is inconsistent. The purpose of the present study was to determine the effects of CG position on healthy adults' knee joint position sense acuity. In a counterbalanced, single-blinded study, 16 healthy young adults (8 female, age: 25.5 y) performed an active knee joint position-matching task with and without (CON) a below-knee (BK), above-knee (AK), or whole-knee (WK) CG in a randomized order on the dominant (CompDom) or the non-dominant leg (CompNon-Dom). We also determined the magnitude of tissue compression by measuring anatomical thigh and calf cross sectional area (CSA) in standing using magnetic resonance imaging (MRI). Subjects had less absolute repositioning error (magnitude of error) in BK compared with CON condition. On the other hand, the analysis of the direction of error (constant error) revealed that in each condition subjects tended to underestimate the target position (AK, BK and CON: 75%; WK: 94%). In WK condition there was a significantly larger negative error (-2.7 ±â€¯3.4) as compared with CON (-1.6 ±â€¯3.7) condition. There also was less variable error, in WK compared to BK and CON conditions, indicating less variability in their position sense using a WK CG, regardless of the underestimation. CG reduced thigh CSA by 4.5 cm2 or 3% and calf CSA by Δ1.3 cm2 or 1%. The position of CG relative to the knee modifies knee JPS. The findings helps us better understand how the application of a WK CG may support athletic activities.

An above-knee compression garment does not improve passive knee joint position sense in healthy adults.

We determined the effects of wearing an above-knee compression garment (CG) on knee joint position sense. Healthy young adults (n = 24, age = 27.46 ± 4.65 years) performed a passive knee position-matching task on an isokinetic dynamometer with each leg separately. We determined the magnitude of compression by measuring anatomical thigh cross sectional area (CSA) in standing using magnetic resonance imaging. Wearing the CG compressed CSA by 2% (t = 2.91, p = 0.010, Cohen's d = 0.68). Repeated measures ANOVA (rANOVA) with three repetition factors (condition: CG, no CG; leg: right dominant, left non-dominant; and target angles: 30°, 45°, 60°) revealed an effect of angles (p < 0.001), where the matching of knee joint position was more accurate at 60° compared to 30° and 45° (p < 0.001). However, CG did not reduce passive joint position sense errors. In fact, joint position error was less without CG (p = 0.014). In conclusion, while CG does compress the thigh it does not afford the purported benefits for proprioception as measured by a target-matching task in the present study.

Randomized, double-blind, and placebo-controlled trial of clenbuterol in denervated muscle atrophy.

Objectives. ß(2)-adrenergic agonists, such as clenbuterol, have been shown to promote the hypertrophy of healthy skeletal muscles and to ameliorate muscle wasting in a few pathological conditions in both animals and humans. We intended to investigate the clinical efficacy of clenbuterol on attenuating denervation-induced muscle atrophy. Methods. A double-blind, placebo-controlled, parallel, and randomized trial was employed. 71 patients, suffering from brachial plexus injuries, were given either clenbuterol (60 µg, bid) or placebo for 3 months. Before and at the end of the study, patients were given physical examinations, biopsies of biceps brachii, electromyograms (EMGs), and other laboratory tests. Results. Compared with placebo treatment, clenbuterol significantly mitigated the decreases in cross-sectional areas of type I and II muscle fibers and alleviated the reduction in fibrillation potential amplitudes, without any adverse effects. Conclusions. Clenbuterol safely ameliorated denervated muscle atrophy in this cohort; thus larger clinical studies are encouraged for this or other ß(2) agonists on denervation-induced muscle atrophy.

Selective neurotization of the median nerve in the arm to treat brachial plexus palsy. Surgical technique.

BACKGROUND: The current method for treatment of median nerve palsy after a brachial plexus injury is unpredictable. On the basis of an anatomic study of the median nerve in the arm, we present a new method of selective neurotization of the median nerve. METHODS: Internal topographic features of the fascicular groups of the median nerve were observed in seventeen cadavera. On the basis of the anatomical results, selective neurotization of the posterior fascicular group of the median nerve in the arm was performed in one patient with a complete brachial plexus palsy. RESULTS: In the distal half of the arm, the branches of the median nerve consistently collect into three fascicular groups, which are located at the anterior, middle, and posterior parts of the median nerve trunk. The anterior fascicular group is composed of the branches to the pronator teres and the flexor carpi radialis, the posterior fascicular group is composed mainly of the anterior interosseous nerve and the branches to the palmaris longus, and the middle fascicular group is made up mostly of the branches to the hand and the flexor digitorum superficialis. A transfer of the full length of the phrenic nerve was used to selectively reinnervate the posterior fascicular group of the median nerve in a patient with a complete brachial plexus palsy. The muscles supplied by the posterior fascicular group regained Grade-4 power, according to the system of the Medical Research Council, sixteen months after surgery. CONCLUSIONS: The typical arrangement of the fascicular groups of the median nerve in the arm favors the technique of selective neurotization, which has been used effectively in one patient to date.

Selective neurotization of the median nerve in the arm to treat brachial plexus palsy. An anatomic study and case report.

BACKGROUND: The current method for treatment of median nerve palsy after a brachial plexus injury is unpredictable. On the basis of an anatomic study of the median nerve in the arm, we present a new method of selective neurotization of the median nerve. METHODS: Internal topographic features of the fascicular groups of the median nerve were observed in seventeen cadavera. On the basis of the anatomical results, selective neurotization of the posterior fascicular group of the median nerve in the arm was performed in one patient with a complete brachial plexus palsy. RESULTS: In the distal half of the arm, the branches of the median nerve consistently collect into three fascicular groups, which are located at the anterior, middle, and posterior parts of the median nerve trunk. The anterior fascicular group is composed of the branches to the pronator teres and the flexor carpi radialis, the posterior fascicular group is composed mainly of the anterior interosseous nerve and the branches to the palmaris longus, and the middle fascicular group is made up mostly of the branches to the hand and the flexor digitorum superficialis. A transfer of the full length of the phrenic nerve was used to selectively reinnervate the posterior fascicular group of the median nerve in a patient with a complete brachial plexus palsy. The muscles supplied by the posterior fascicular group regained Grade-4 power, according to the system of the Medical Research Council, sixteen months after surgery. CONCLUSIONS AND CLINICAL RELEVANCE: The typical arrangement of the fascicular groups of the median nerve in the arm favors the technique of selective neurotization, which has been used effectively in one patient to date.