Early stage transplantation of bone marrow cells markedly ameliorates copper metabolism and restores liver function in a mouse model of Wilson disease

<p>Abstract</p> <p>Background</p> <p>Recent studies have demonstrated that normal bone marrow (BM) cells transplantation can correct liver injury in a mouse model of Wilson disease (WD). However, it still remains unknown when BM cells transplantation should be administered. The aim of this study was to investigate the potential impact of normal BM cells transplantation at different stages of WD to correct liver injury in toxic milk (tx) mice.</p> <p>Methods</p> <p>Recipient tx mice were sublethally irradiated (5 Gy) prior to transplantation. The congenic wild-type (DL) BM cells labeled with CM-DiI were transplanted via caudal vein injection into tx mice at the early (2 months of age) or late stage (5 months of age) of WD. The same volume of saline or tx BM cells were injected as controls. The DL donor cell population, copper concentration, serum ceruloplasmin oxidase activity and aspartate aminotransferase (AST) levels in the various groups were evaluated at 1, 4, 8 and 12 weeks post-transplant, respectively.</p> <p>Results</p> <p>The DL BM cells population was observed from 1 to 12 weeks and peaked by the 4^thweek in the recipient liver after transplantation. DL BM cells transplantation during the early stage significantly corrected copper accumulation, AST across the observed time points and serum ceruloplasmin oxidase activity through 8 to 12 weeks in tx mice compared with those treated with saline or tx BM cells (all <it>P </it>< 0.05). In contrast, BM cells transplantation during the late stage only corrected AST levels from 4 to 12 weeks post-transplant and copper accumulation at 12 weeks post-transplant (all <it>P </it>< 0.05). No significant difference was found between the saline and tx BM cells transplantation groups across the observed time points (<it>P </it>> 0.05).</p> <p>Conclusions</p> <p>Early stage transplantation of normal BM cells is better than late stage transplantation in correcting liver function and copper metabolism in a mouse model of WD.</p

Hydrogen Sulfide Protects against Chemical Hypoxia-Induced Cytotoxicity and Inflammation in HaCaT Cells through Inhibition of ROS/NF-κB/COX-2 Pathway

Hydrogen sulfide (H2S) has been shown to protect against oxidative stress injury and inflammation in various hypoxia-induced insult models. However, it remains unknown whether H2S protects human skin keratinocytes (HaCaT cells) against chemical hypoxia-induced damage. In the current study, HaCaT cells were treated with cobalt chloride (CoCl2), a well known hypoxia mimetic agent, to establish a chemical hypoxia-induced cell injury model. Our findings showed that pretreatment of HaCaT cells with NaHS (a donor of H2S) for 30 min before exposure to CoCl2 for 24 h significantly attenuated CoCl2-induced injuries and inflammatory responses, evidenced by increases in cell viability and GSH level and decreases in ROS generation and secretions of IL-1β, IL-6 and IL-8. In addition, pretreatment with NaHS markedly reduced CoCl2-induced COX-2 overexpression and PGE2 secretion as well as intranuclear NF-κB p65 subunit accumulation (the central step of NF-κB activation). Similar to the protective effect of H2S, both NS-398 (a selective COX-2 inhibitor) and PDTC (a selective NF-κB inhibitor) depressed not only CoCl2-induced cytotoxicity, but also the secretions of IL-1β, IL-6 and IL-8. Importantly, PDTC obviously attenuated overexpression of COX-2 induced by CoCl2. Notably, NAC, a ROS scavenger, conferred a similar protective effect of H2S against CoCl2-induced insults and inflammatory responses. Taken together, the findings of the present study have demonstrated for the first time that H2S protects HaCaT cells against CoCl2-induced injuries and inflammatory responses through inhibition of ROS-activated NF-κB/COX-2 pathway

Ultrasonography Comparison of Diaphragm Morphological Structure and Function in Young and Middle-Aged Subjects with and without Non-Specific Chronic Low Back Pain: A Case-Control Study

Background. It is reported that impaired postural control in patients with non-specific chronic low back pain (NCLBP) was associated with “core” trunk muscle incoordination. However, as the diaphragm is an important component of the “core” deep trunk muscle group, we still know little about the potential relationship between diaphragm dysfunction and NCLBP. Objectives. This case-control study is intended to investigate the changes of diaphragm morphological structure and function in young and middle-aged subjects with and without NCLBP by ultrasound evaluation and its possible validity in predicating the occurrence of NCLBP. Methods. 31 subjects with NCLBP (NCLBP group) and 32 matched healthy controls (HC group) were enrolled in this study. The diaphragm thickness at the end of inspiration (Tins) or expiration (Texp) during deep breathing was measured through B-mode ultrasound, and the diaphragm excursion (Texc) was estimated at deep breathing through M-mode ultrasound. The diaphragm thickness change rate (Trate) was calculated by the formula: Trate=Tins−Texp/Texp×100%. Results. Compared with the HC group, the NCLBP group had a significant smaller degree of Tins (t = −3.90, P<0.001), Texp (Z = −2.79, P=0.005), and Trate (t = −2.03, P=0.047). However, there was no statistical difference in Texc between the two groups (t = −1.42, P=0.161). The binary logistic regression analysis indicated that Trate (OR = 16.038, P=0.014) and Texp (OR = 7.714, P=0.004) were potential risk factors for the occurrence of NCLBP. Conclusions. The diaphragm morphological structure and function were changed in young and middle-aged subjects with NCLBP, while the diaphragm thickness change rate (Trate) and diaphragm thickness at the end of expiration (Texp) may be conductive to the occurrence of NCLBP. Furthermore, these findings may suggest that abnormal diaphragm reeducation is necessary for the rehabilitation of patients with NCLBP

Cerebellar transcranial direct current stimulation modulates anticipatory postural adjustments in healthy adults

During forward swinging of the arm, the central nervous system must anticipate the effect of upraising upon the body. Little is known about the cerebellar network that coordinates these anticipatory postural adjustments (APAs). Stimulating different cerebellar regions with transcranial direct current stimulation (tDCS) and with different polarities modulated the APAs. We used surface electromyography (sEMG) to measure muscle activities in a bilateral rapid shoulder flexion task. The onset of APAs was altered after tDCS over the vermis, while the postural stability and the kinematics of arm raising were not affected. To our knowledge, this is the first human cerebellar-tDCS (c-tDCS) study to separate cerebellar involvement in core muscle APAs in bilateral rapid shoulder flexion. These data contribute to our understanding of the cerebellar network supporting APAs in healthy adults. Modulated APAs of the erector spinae by tDCS on the vermis may be related to altered cerebellar brain inhibition (CBI), suggesting the importance of the vermal-cerebral connections in APAs regulation

Cortical Representations of Transversus Abdominis and Multifidus Muscles Were Discrete in Patients with Chronic Low Back Pain: Evidence Elicited by TMS

Introduction. The transversus abdominis (TVA) and multifidus (MF) muscles are the main segmental spinal stabilizers that are controlled by the primary motor cortex of the brain. However, relocations of the muscle representation in the motor cortex may occur after chronic lower back pain (cLBP); it still needs more evidence to be proven. The current study was aimed at applying transcranial magnetic stimulation (TMS) to investigate the changes of representation of TVA and MF muscles at the cortical network in individuals with cLBP. Methods. Twenty-four patients with cLBP and 12 age-matched healthy individuals were recruited. Responses of TVA and MF to TMS during muscle contraction were monitored and mapped over the contralateral cortex using a standardized grid cap. Maps of the center of gravity (CoG), area, volume, and latency were analyzed, and the asymmetry index was also computed and compared. Results. The locations of MF CoG in cLBP individuals were posterior and lateral to the CoG locations in healthy individuals. In the healthy group, the locations of TVA and MF CoG were closed to each other in both the left and right hemispheres. In the cLBP group, these two locations were next to each other in the right hemisphere but discrete in the left hemisphere. In the cLBP group, the cortical motor map of TVA and MF were mutually symmetric in five out of eleven (45.5%) subjects and leftward asymmetric in four out of ten (40.0%) subjects. Conclusions. Neural representations of TVA and MF muscles were closely organized in both the right and left motor cortices in the healthy group but were discretely organized in the left motor cortex in the cLBP group. This provides strong support for the neural basis of pathokinesiology and clinical treatment of cLBP

Full Step Cycle Kinematic and Kinetic Comparison of Barefoot Walking and a Traditional Shoe Walking in Healthy Youth: Insights for Barefoot Technology

Objective. Barefoot technology shoes are becoming increasingly popular, yet modifications are still needed. The present study aims to gain valuable insights by comparing barefoot walking to neutral shoe walking in a healthy youth population. Methods. 28 healthy university students (22 females and 6 males) were recruited to walk on a 10-meter walkway both barefoot and in neutral running shoes at their comfortable walking speed. Full step cycle kinematic and kinetic data were collected using an 8-camera motion capture system. Results. In the early stance phase, the knee extension moment (MK1), the first peak absorbed joint power at the knee joint (PK1), and the flexion angle of knee/dorsiflexion angle of the ankle were significantly reduced when walking in neutral running shoes. However, in the late stance, barefoot walking resulted in decreased hip joint flexion moment (MH2), second peak extension knee moment (MK3), hip flexors absorbed power (PH2), hip flexors generated power (PH3), second peak absorbed power by knee flexors (PK2), and second peak anterior-posterior component of joint force at the hip (APFH2), knee (APFK2), and ankle (APFA2). Conclusions. These results indicate that it should be cautious to discard conventional elements from future running shoe designs and rush to embrace the barefoot technology fashion

Pain Catastrophizing Is Related to Static Postural Control Impairment in Patients with Nonspecific Chronic Low Back Pain: A Cross-Sectional Study

Purpose. Pain catastrophizing may contribute to the altered trunk muscle activity in patients with nonspecific chronic low back pain (NSCLBP). It is unclear if pain catastrophizing influences static postural control in patients with NSCLBP. This study aimed to investigate the relationship between pain catastrophizing and static postural control in NSCLBP patients. Methods. Sixty-eight participants with NSCLBP and 40 healthy participants were recruited. Postural control was assessed by the sway area and the sway length of the center of pressure (COP) during balance tests. Pain catastrophizing in participants with NSCLBP was assessed by the Pain Catastrophizing Scale (PCS). Bilateral transversus abdominis (TrA) activation was evaluated by ultrasound imaging-measured percent change in muscle thickness. Associations between COP parameter and PCS/subscales of PCS were examined by multiple linear regression (MLR). Results. Our results observed a larger COP sway area in NSCLBP group under eyes-closed condition p<0.001 and a lower level of voluntary activation of the bilateral TrA p<0.001, compared with the healthy control group. The MLR analyses revealed that the COP area sway under eyes-closed condition was significantly associated with the PCS score/helplessness score of PCS, voluntary activation of the left TrA, and age in participants with NSCLBP (β = 0.222/0.236, 0.341/0.344, and 0.328/0.325; p=0.045/0.033, 0.002, and 0.004, resp.). Conclusions. Static postural control was associated with pain catastrophizing, voluntary activation of TrA, and age in participants with NSCLBP. This indicated that pain catastrophizing may affect postural control and should be considered when interpreting balance test results and managing NSCLBP

Home-based rehabilitation training with human key point detection for chronic low back pain patients: a randomized controlled trial protocol

Abstract Background Core stability exercise (CSE) is a globally acknowledged intervention for managing chronic low back pain. However, the sustained adherence of patients with chronic low back pain to CSE can be challenging, mainly due to the absence of supervision and guidance from physical therapists during home-based exercise sessions. Consequently, exercise compliance tends to decline, resulting in suboptimal long-term effectiveness of the intervention. In this trial, our primary aim is to evaluate the potential therapeutic equivalence between home-based rehabilitation training employing key point identification technology and exercise guidance administered in a hospital setting. Methods In this trial, we will randomly assign 104 adults with chronic low back pain (CLBP) to either an intervention or control group, with 52 participants in each group. Both interventions will consist of three weekly 0.5-h sessions of core stability exercise (CSE). The intervention group will engage in home rehabilitation training utilizing key identification technology for movement, while the control group will perform supervised exercises in a hospital setting. Outcome assessments will be conducted at 4 weeks and 16 weeks after randomization. The primary outcome measure will be the change in pain intensity based on numeric rating scale (NRS scores) from baseline to 4 weeks. Secondary outcomes will include changes in physical function (measured by the Oswestry Disability Index (ODI)) and lumbar spine mobility as well as activity participation and treatment satisfaction. Discussion If home-based rehabilitation method is demonstrated to be non-inferior or even superior to traditional face-to-face exercise guidance, it could significantly advance the adoption of digital medical care and contribute to improving the overall health of the population. Trial registration NCT05998434 . Registered on 16 August 2023