MicroRNA-146a gene transfer ameliorates senescence and senescence-associated secretory phenotypes in tendinopathic tenocytes.

OBJECTIVE: Tendinopathy is influenced by multiple factors, including chronic inflammation and aging. Senescent cells exhibit characteristics such as the secretion of matrix-degrading enzymes and pro-inflammatory cytokines, collectively known as senescence-associated secretory phenotypes (SASPs). Many of these SASP cytokines and enzymes are implicated in the pathogenesis of tendinopathy. MicroRNA-146a (miR-146a) blocks senescence by targeting interleukin-1ß (IL-1ß) receptor-associated kinase 4 (IRAK-4) and TNF receptor-associated factor 6 (TRAF6), thus inhibiting NF-κB activity. The aims of this study were to (1) investigate miR-146a expression in tendinopathic tendons and (2) evaluate the role of miR-146a in countering senescence and SASPs in tendinopathic tenocytes. METHODS: MiR-146a expression was assessed in human long head biceps (LHB) and rat tendinopathic tendons by in situ hybridization. MiR-146a over-expression in rat primary tendinopathic tenocytes was achieved by lentiviral vector-mediated precursor miR-146a transfer (LVmiR-146a). Expression of various senescence-related markers was analyzed by quantitative reverse transcription polymerase chain reaction (qRT-PCR), immunoblotting and immunofluorescence. MiR-146a expression showed a negative correlation with the severity of tendinopathy in human and rat tendinopathic tendons (p<0.001). RESULTS: Tendinopathic tenocyte transfectants overexpressing miR-146a exhibited downregulation of various senescence and SASP markers, as well as the target molecules IRAK-4 and TRAF6, and the inflammatory mediator phospho-NF-κB. Additionally, these cells showed enhanced nuclear staining of high mobility group box 1 (HMGB1) compared to LVmiR-scramble-transduced controls in response to IL-1ß stimulation. CONCLUSIONS: We demonstrate that miR-146a expression is negatively correlated with the progression of tendinopathy. Moreover, its overexpression protects tendinopathic tenocytes from SASPs and senescence through the IRAK-4/TRAF6/NF-kB pathway.

Beyond traditional therapies: a network meta-analysis on the treatment efficacy for chronic phantom limb pain.

BACKGROUND: Phantom limb pain (PLP) frequently affects individuals with limb amputations. When PLP evolves into its chronic phase, known as chronic PLP, traditional therapies often fall short in providing sufficient relief. The optimal intervention for chronic PLP remains unclear. OBJECTIVE: The objectives of this network meta-analysis (NMA) were to examine the efficacy of different treatments on pain intensity for patients with chronic PLP. EVIDENCE REVIEW: We searched Medline, EMBASE, Cochrane CENTRAL, Scopus, and CINAHL EBSCO, focusing on randomized controlled trials (RCTs) that evaluated interventions such as neuromodulation, neural block, pharmacological methods, and alternative treatments. An NMA was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The primary outcome was pain score improvement, and the secondary outcomes were adverse events. FINDINGS: The NMA, incorporating 12 RCTs, indicated that neuromodulation, specifically repetitive transcranial magnetic stimulation, provided the most substantial pain improvement when compared with placebo/sham groups (mean difference=-2.9 points, 95% CI=-4.62 to -1.18; quality of evidence (QoE): moderate). Pharmacological intervention using morphine was associated with a significant increase in adverse event rate (OR=6.04, 95% CI=2.26 to 16.12; QoE: low). CONCLUSIONS: The NMA suggests that neuromodulation using repetitive transcranial magnetic stimulation may be associated with significantly larger pain improvement for chronic PLP. However, the paucity of studies, varying patient characteristics across each trial, and absence of long-term results underscore the necessity for more comprehensive, large-scale RCTs. PROSPERO REGISTRATION NUMBER: CRD42023455949.

International collaboration between low-middle-income and high-income institutions to improve radiation therapy care delivery.

INTRODUCTION: The Philippines is a lower-middle-income island country with over 153 000 new cancer diagnosis each year. Despite many patients needing radiotherapy as part of disease management, there remains limitations to access. Currently, the Philippines has 50 linear accelerator facilities serving a population of 110 million. However, given the recommendation of 1 linear accelerator for every 250 thousand people, it is evident that the demand for accessible radiotherapy resources is significantly underserved in the country. This paper outlines the collaboration between GenesisCare Solutions (GCS) and Fairview Cancer Center (FCC) to address efficiency and access within the radiotherapy department at FCC. METHODS: Through international collaboration between GCS and FCC, areas for improvement were identified and categorized into four domains: Dosimetry quality, Patient workflow, Data & Reporting, and Information Technology (IT) Infrastructure. Action plans were developed then implemented. A baseline measurement was obtained for each domain, and post-implementation evaluation undertaken at 3 months, 6 months, and 12 months. Data captured within the electronic medical record system was extrapolated, and average treatment times were established for pre- and post-engagement. A paired, 2-tailed t-test was used for statistical analysis of outcome parameters using IBM SPSS version 23 for all statistics. RESULTS: Twelve months post-initial engagement, all four domains saw positive outcomes. Improved plan quality linked to Intensity Modulated Radiotherapy (IMRT) utilization rates saw an increase from 20% to 54%. A significant reduction in patient average wait times was also observed, from 27 to 17 min (p ≤ 0.001). Prior to engagement, tracking patient demographics and diagnosis was not prioritized, post engagement an average of 92% diagnosis entry compliance was achieved. CONCLUSION: Through the collaboration of GCS and FCC, objectives in all action plan domains were achieved, highlighting the benefits of collaboration between low-middle-income and high-income institutions.

Daily supplement of sesame oil prevents postmenopausal osteoporosis via maintaining serum estrogen and aromatase levels in rats.

Estrogen deficiency is one of the main causes of postmenopausal osteoporosis in elderly women. Hormone replacement therapy has been employed to manage postmenopausal osteoporosis; however, it has raised concerns related to heart attacks and breast cancer. Sesame oil has been reported to affect sex hormone status. The aim of the present study is to evaluate the effect of sesame oil supplement on postmenopausal osteoporosis in rats. We used female Sprague Dawley rats that underwent bilaterally ovariectomy (OVX) as an experimental postmenopausal osteoporosis animal model. These rats were orally administrated sesame oil (0.25 or 0.5 mL/kg/day) for four months as the therapeutic group. We assessed bone mineral density (BMD) and the levels of osteocalcin, procollagen-I C-terminal propeptide (PICP), collagen cross-linked N-telopeptide (NTx), estradiol, and aromatase in the sera. The daily supplementation of sesame oil significantly increased BMD, serum osteocalcin levels, and trabecular areas in the OVX-treated rats. Sesame oil also elevated serum PICP levels and decreased NTx levels in these rats. Furthermore, sesame oil effectively maintained serum estradiol and aromatase levels in the OVX-induced osteoporosis rats. In conclusion, daily supplementation of sesame oil prevents postmenopausal osteoporosis by maintaining serum estrogen and aromatase levels, while also modulating the imbalance between bone formation and resorption in osteoporosis rats.

The use of ultrasound for monitoring reduction and ulnar nerve subluxation in pediatric humeral supracondylar fractures.

BACKGROUND: Traditional treatment for displaced humeral supracondylar fractures (SCFs) in children involves closed reduction (CR) under fluoroscopic guidance, percutaneous pinning, and immobilization with a long-arm cast. This study aims to explore the viability of using radiation-free ultrasound (US) for guiding CR and tracking ulnar nerve dynamics during medial pinning, contrasting the US method with the conventional cross pinning technique. MATERIALS AND METHODS: We assessed 70 children with acute displaced SCFs. The US group (n = 30) underwent US-guided reduction, whereas the traditional group (n = 40) underwent fluoroscopy-guided reduction. Both groups received percutaneous cross pinning and subsequent cast immobilization. Postoperative outcomes were compared between the two methods after a 6-month follow-up. In the US group, ultrasonography assessed fracture displacement distances before and after CR. The angle at which the ulnar nerve relocated to the cubital tunnel during elbow extension was documented using real-time US monitoring during medial pinning. RESULTS: The US group demonstrated improved reduction accuracy, increased range of motion, superior restoration of both Baumann and Humeroulnar angles, and a decreased incidence of malunions compared to the traditional group (all p < 0.05). The ultrasonographic measurement of fracture displacement was comparable with that of fluoroscopy (intraclass correlation coefficient > 0.90). In the US group, no ulnar nerve injury was noted, compared to 2.5 % in the traditional group, and real-time US observations revealed ulnar nerve hypermobility, with 53.3 % of patients exhibiting anterior ulnar nerve subluxation at 120° elbow flexion, 40 % at 90°, 16.7 % at 60°, and none at 30° flexion. CONCLUSION: Ultrasound is as reliable as fluoroscopy for evaluating fracture reductions. The use of intra-operative ultrasound significantly improves reduction accuracy and radiographic outcomes while reducing the risk of ulnar nerve injury.

The Pulsed Nd:YAG Laser Therapy Enhanced Nerve Regeneration via Apoptosis Inhibition in a Rat Crushed Sciatic Nerve Model.

The study was aimed to validate the efficacy of the pulsed Nd:YAG laser on nerve regeneration in a rat sciatic nerve crushed model. 54 Wistar rats were randomly assigned into three groups: shame control, crush control, and laser treated group. For the laser treated group, the pulsed Nd:YAG laser (10 Hz) with 350 mJ per pulse in energy density and 50 J/cm2 in fluence was applied extracorporeally at the lesion site for 12 min to daily deliver 500 J immediately and consecutive 9 days following the crush injury. At week 1, the apoptosis-related activities in the injured nerve were examined (n = 8/each group). The sciatic functional index (SFI) was measured preoperatively and weekly until 4 weeks after the index procedure. The injured nerve and the innervated gastrocnemius muscle histology were assessed at week 4 (n = 10/each group). At week 1, the laser group showed the significant less TUNEL-positive ratio (P < 0.05), and the lower expression of cleaved caspase3/procaspase-3 and beclin-2/beclin-2-associated protein X ratios compared with the crush control. Furthermore, the laser group revealed significantly better SFI since week 1 and throughout the study (P < 0.05, all) compared with the crush control. At week 4, the laser group showed significantly higher axon density, lower myelin g-ratio, and the corresponding higher glycogen expression (P < 0.05, all) in the gastrocnemius muscle compared with those in the crush control. The pulsed Nd:YAG might enhance the injured nerve regeneration via apoptosis inhibition.

Is delayed fixation worthwhile in patients with long bone fracture concomitant with mild traumatic brain injury? A propensity score-matched study.

INTRODUCTION: Early definite treatment for orthopedic patients is strongly advocated. However, a consensus has not been reached on the optimal timing of long bone fracture fixation for patients with associated mild traumatic brain injury (TBI). Surgeons lack evidence on the basis on which they should decide on the operation timing. METHODS: We retrospectively reviewed the data of patients with mild TBI and lower extremity long bone fractures from 2010 to 2020. The patients receiving internal fixation within and after 24 h were defined as the early- and delayed-fixation groups. We compared the discharge Glasgow Coma Scale (GCS) scores, lengths of stay, and in-hospital complications. Propensity score matching (PSM) with multiple adjusted variables and a 1:1 matching ratio was applied to reduce selection bias. RESULTS: In total, 181 patients were enrolled; 78 (43.1%) and 103 (56.9%) patients received early and delayed fracture fixation, respectively. After matching, each group had 61 participants and were statistically identical. The delayed group did not have better discharge GCS scores (early vs. delayed: 15.0 ± 0 vs. 15.0 ± 0.1; p = 0.158). The groups did not differ in their lengths of hospital stay (15.3 ± 10.6 vs. 14.8 ± 7.9; p = 0.789), intensive care unit stay (2.7 ± 4.3 vs. 2.7 ± 3.8; p = 0.947), or incidence of complications (23.0% vs. 16.4%; p = 0.494). CONCLUSIONS: Delayed fixation for patients with lower extremity long bone fractures concurrent with mild TBI does not result in fewer complications or improved neurologic outcomes compared with early fixation. Delaying fixation may not be necessary to prevent the second hit phenomenon and has not demonstrated any clear benefits.

Comparison of intra-articular injection of ArtiAid®-Mini with Ostenil®-Mini for trapeziometacarpal osteoarthritis: A double-blind, prospective, randomized, non-inferiority trial.

OBJECTIVES: This study aims to compare the effectiveness and safety of intra-articular hyaluronic acid (HA) injections of ArtiAid®-Mini (AAM) and Ostenil®-Mini (OM) for the treatment of trapeziometacarpal joint osteoarthritis. PATIENTS AND METHODS: Between February 2018 and April 2020, this 24-week, double-blind, prospective, randomized, non-inferiority trial included a total of 17 patients (8 males, 9 females; mean age: 60.3±9.5 years; range, 42 to 76 years) who were treated with either intra-articular AAM (n=8) or OM (n=9). The primary outcome was pain according to a change in Visual Analog Scale (VAS) at 12 weeks after the last injection. The secondary outcomes included the change of VAS at Weeks 2, 4, and 24 after the injection, satisfaction, range of motion (ROM) of trapeziometacarpal joint, pinch strength, grip strength, and adverse events at Weeks 2, 4, 12, and 24 after the injection. RESULTS: Eight patients with AAM and eight patients with OM completed the follow-up. No significant differences in primary and secondary outcomes were observed between the two groups at baseline and each time point (p>0.05). The intra-group differences were significant in each time point. CONCLUSION: The intra-articular injection of either AAM or OM is effective and safe for patients with trapeziometacarpal osteoarthritis up to 24 weeks.

Comparison of ultrasound and dorsal tangential view for dorsal cortex screw penetration in volar plating of the distal radius.

We compared the accuracy of the fluoroscopic dorsal tangential view (DTV) and an ultrasound (US) examination in detecting dorsal screw penetration during volar distal radius plating. In six fresh cadaveric distal radii, seven periarticular locking screws in two rows for each plate were inserted according to the measured length using a depth gauge and then replaced with another that was 1 and 2 mm longer, respectively. The actual protruded length of each screw was determined using computed tomography (CT) images. The accuracy of US and DTV measurements was determined using the intraclass correlation coefficient (ICC), as both measurements were compared with CT measurements. The ICC of US and DTV was 0.96 and 0.75, respectively, for all screws. After excluding the data for proximal-row screws, the ICC of US remained unchanged at 0.96, and that of DTV improved to 0.86. The ICC of US was significantly higher than that of DTV (p < 0.01). US had a 100% detection rate for screw protrusion of more than 1.0 mm. US examination showed excellent consistency with CT measurements and its accuracy was not affected by screw location. US might thus be a practical tool for detecting dorsal cortex screw penetration during volar distal radius plating.

Jigless Knotless Internal Brace Versus Other Minimal Invasive Achilles Tendon Repair Techniques in Biomechanical Testing Simulating the Progressive Rehabilitation Protocol.

The jigless knotless internal brace surgery (JKIB), an alternative method for minimal invasive surgery (MIS) repair of acute Achilles tendon rupture, has advantages of preventing sural-nerve injury in MIS and superficial wound infection in open surgery, as previous clinical research demonstrates. However, no comparative study on the biomechanical performance between JKIB and other MIS techniques has been reported until now. In this study, 50 fresh porcine Achilles tendons were used to compare the JKIB with open surgery (two-stranded Krachow suture) with other MIS techniques, including Percutaneus Achilles Repair System (PARS), Speedbridge (SB), and Achillon Achilles Tendon Suture System (ACH), using a biomechanical testing with cyclic loading at 1 Hz. This test was used to simulate a progressive rehabilitation protocol where 20 to 100 N was applied in the first 250 cycles, followed by 20 to 190 N in the second 250 cycles, and then 20 to 369 N in the third 250 cycles. The cyclic displacement after 10, 100 and 250 cycles were recorded. The survived cycles were defined as a sudden drop in measured load. In survived cycles, the JKIB group (552.3 ± 72.8) had significantly higher cycles than the open, PARS, and ACH groups (204.3 ± 33.3, 395.9 ± 96.0, and 397.1 ± 80.9, respectively, p < .01) as analyzed by post hoc analysis, but no significant difference as compared with the SB group (641.6 ± 48.7). In cyclic displacement after 250 cyclic loadings, the JKIB group (11.29 ± 1.29) showed no significant difference as compared with PARS, SB, and ACH groups (12.21 ± 1.18, 9.80 ± 0.80, and 11.57 ± 1.10 mm, respectively) and significant less displacement than the open group (14.50 ± 1.85, p < .01). These findings suggest that JKIB could be an option for acute Achilles tendon repair in the MIS fashion due to no larger cyclic elongation compared with other MIS techniques.

Factors associated with falls in patients with knee osteoarthritis: A cross-sectional study.

Falls represent an important adverse effect associated with knee osteoarthritis and result in a significant financial burden on the healthcare system. Therefore, identification of fall predictors is essential to minimize fall incidence. However, few studies have investigated falls and fall predictors, particularly focused on the fear of falls and proprioception. In this study, we investigated significant fall predictors in patients with knee osteoarthritis in Malang, Indonesia. Our findings may serve as useful guidelines to develop geriatric fall prevention programs. This cross-sectional survey using purposive sampling was performed between April and July 2021 and included 372 participants. We recorded the following data: sociodemographic and medical history questionnaire responses, visual analog scale scores, Hopkins falls grading scale scores, Fall Efficacy Scale-International scores, proprioception test findings, knee injury and osteoarthritis outcome score (KOOS), range of motion (ROM), chair stand test and the timed up and go test performance. Data were analyzed using the chi-square and t tests, and multivariate logistic regression to determine significant fall predictors. Multivariate logistic regression analysis showed a lower risk of falls in patients with better proprioception and ROM than in the other groups (odds ratio 0.55 vs 0.96). The risk of falls was higher in patients with higher KOOS symptoms, fear of falls, diagnosis of low back pain and diabetes mellitus, and increased body mass index than in the other groups (odds ratio 1.41, 2.65, 1.27, 3.45, and 1.10, respectively. Our study shows that knee proprioception and ROM serve as protective factors against falls, whereas KOOS symptoms, fear of falls, low back pain, diabetes mellitus, and body mass index were associated with a high risk of falls, with diabetes mellitus and fear of falls being the most significant risk factors. These findings may be useful to policy makers to develop a fall prevention program that can be implemented in community health care centers across Indonesia to deliver individualized, person-centered care and improve fall prevention strategies through a systematic process comprising evaluation, intervention, and monitoring to minimize fall risk.

Triptolide Attenuates Muscular Inflammation and Oxidative Stress in a Delayed-Onset Muscle Soreness Animal Model.

Delayed-onset muscle soreness (DOMS) is associated with exercise-induced muscle damage and inflammation, which is mainly caused by prolonged eccentric exercise in humans. Triptolide, an extract from the Chinese herb Tripterygium wilfordii Hook F, has been used for treating autoimmune and inflammatory diseases in clinical practice. However, whether triptolide attenuates acute muscle damage is still unclear. Here, we examined the effect of triptolide on carrageenan-induced DOMS in rats. Rats were injected with 3% of carrageenan into their muscles to induce acute left gastrocnemius muscular damage, and triptolide treatment attenuated carrageenan-induced acute muscular damage without affecting hepatic function. Triptolide can significantly decrease lipid hydroperoxide and nitric oxide (NO) levels, proinflammatory cytokine production, and the activation of nuclear factor (NF)-ĸB, as well as increase a reduced form of glutathione levels in carrageenan-treated rat muscles. At the enzyme levels, triptolide reduced the inducible nitric oxide synthase (iNOS) expression and muscular myeloperoxidase (MPO) activity in carrageenan-treated DOMS rats. In conclusion, we show that triptolide can attenuate muscular damage by inhibiting muscular oxidative stress and inflammation in a carrageenan-induced rat DOMS model.

Single Injection of Cross-Linked Hyaluronate in Knee Osteoarthritis: A 52-Week Double-Blind Randomized Controlled Trial.

Background: to compare the 52-week effectiveness and safety between HYAJOINT Plus (HJP) and Durolane in knee osteoarthritis (OA) treatment. Methods: consecutive patients received a single injection of 3 mL HJP or Durolane. The primary outcome was a visual analog scale (VAS) pain measurement at 26 weeks post-injection. Secondary outcomes included other clinical, satisfaction, and safety assessments for 52 weeks. Results: 142 patients were equally randomized. At week 26, the HJP group had less VAS pain than the Durolane group (18.1 ± 9.5 versus 24.4 ± 14.0, p = 0.001). Both groups showed improvement in their VAS pain and stiffness scores, and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and total scores for 52 weeks after injection (p < 0.001). However, the HJP group showed lower VAS pain and stiffness scores, reduced WOMAC pain and stiffness scores, a shorter Timed "Up & Go" (TUG) time, and a higher satisfaction score than the Durolane group for 39 weeks (p < 0.05). Only mild and self-limited adverse events occurred (40.8%). Conclusion: While a single injection of either HJP or Durolane is safe and effective for at least 52 weeks, HJP provided superior improvement in terms of VAS pain and stiffness scores, WOMAC pain and stiffness scores, and satisfaction score within 39 weeks of treatment.

Interleukin-23 Mediates Osteoclastogenesis in Collagen-Induced Arthritis by Modulating MicroRNA-223.

Interleukin-23 (IL-23) plays a pivotal role in rheumatoid arthritis (RA). IL-23 and microRNA-223 (miR-223) are both up-regulated and mediate osteoclastogenesis in mice with collagen-induced arthritis (CIA). The aim of this study was to examine the association between IL-23 and miR-223 in contributing to osteoclastogenesis and arthritis. Levels of IL-23p19 in joints of mice with CIA were determined. Lentiviral vectors expressing short hairpin RNA (shRNA) targeting IL-23p19 and lisofylline (LSF) were injected intraperitoneally into arthritic mice. Bone marrow-derived macrophages (BMMs) were treated with signal transducers and activators of transcription 4 (STAT4) specific shRNA and miR-223 sponge carried by lentiviral vectors in response to IL-23 stimulation. Treatment responses were determined by evaluating arthritis scores and histopathology in vivo, and detecting osteoclast differentiation and miR-223 levels in vitro. The binding of STAT4 to the promoter region of primary miR-223 (pri-miR-223) was determined in the Raw264.7 cell line. IL-23p19 expression was increased in the synovium of mice with CIA. Silencing IL-23p19 and inhibiting STAT4 activity ameliorates arthritis by reducing miR-223 expression. BMMs from mice in which STAT4 and miR-223 were silenced showed decreased osteoclast differentiation in response to IL-23 stimulation. IL-23 treatment increased the expression of miR-223 and enhanced the binding of STAT4 to the promoter of pri-miR-223. This study is the first to demonstrate that IL-23 promotes osteoclastogenesis by transcriptional regulation of miR-223 in murine macrophages and mice with CIA. Furthermore, our data indicate that LSF, a selective inhibitor of STAT4, should be an ideal therapeutic agent for treating RA through down-regulating miR-223-associated osteoclastogenesis.

Cross-Linked Hyaluronate and Corticosteroid Combination Ameliorate the Rat Experimental Tendinopathy through Anti-Senescent and -Apoptotic Effects.

The combination of cross-linked hyaluronate (cHA) and corticosteroid showed more rapid pain or functional improvement in knee osteoarthritis and adhesive capsulitis. However, rare evidence of this combination in treating tendinopathy has been reported. We hypothesized that the specific formulations of cHA and dexamethasone (DEX) conferred amelioration of tendinopathy via anti-apoptosis and anti-senescence. In this controlled laboratory study, primary tenocytes from the human tendinopathic long head of biceps were treated with three cHA formulations (cHA:linealized HA = 80:20, 50:50, and 20:80) + DEX with or without IL-1ß stimulation. Cell viability, inflammatory cytokines, tendon-related proliferation markers, matrix metalloproteinases (MMPs), senescent markers, and apoptosis were examined. The in vivo therapeutic effects of the selected cHA + DEX combinations were evaluated in a collagenase-induced rat patellar tendinopathy model. The expression levels of inflammatory mediators, including IL-1ß, IL-6, COX-2, MMP-1, and MMP-3 were significantly reduced in all cHA + DEX-treated tenocytes (p < 0.05, all). The cHA (50:50) + DEX and cHA (20:80) + DEX combinations protected tenocytes from cytotoxicity, senescence, and apoptosis induced by DEX in either IL-1ß stimulation or none. Furthermore, the two combinations significantly improved the rat experimental tendinopathy by reducing ultrasound feature scores and histological scores as well as the levels of apoptosis, senescence, and senescence-associated secretory phenotypes (p < 0.05, all). We identified two specific cHA formulations (cHA (50:50) and cHA (20:80)) + DEX that could ameliorate tendinopathy through anti-senescence and -apoptosis without cytotoxicity. This study provides a possible approach to treating tendinopathy using the combination of two well-known agents.

Design and Investigation of an Eco-Friendly Wound Dressing Composed of Green Bioresources- Soy Protein, Tapioca Starch, and Gellan Gum.

In the fields of biomedicine and tissue engineering, natural polymer-based tissue-engineered scaffolds are used in multiple applications. As a plant-derived polymer, soy protein, containing multiple amino acids, is structurally similar to components of the extra-cellular matrix (ECM) of tissues. It is biological safety provided a good potential to be material for pure natural scaffolds. Moreover, as a protein, the properties of soy protein can be easily adjusted by modifying the functional groups on it. In addition, by blending soy protein with other synthetic and natural polymers, the mechanical characteristics and bioactive behavior of scaffolds can be facilitated for a variety of bio-applications. In this research, soy protein and polysaccharides tapioca starch are used, and gellan gum to develop a protein-based composite scaffold for cell engineering. The morphology and surface chemical composition are characterized via micro-computed tomography (micro-CT), scanning electron microscope (SEM), and fourier-transform infrared (FTIR) spectroscopy. The soy/tapioca/gellan gum (STG) composite scaffolds selectively help the adhesion and proliferation of L929 fibroblast cells while improving the migration of L929 fibroblast cells in STG composite scaffolds as the increase of soy protein proportion of the scaffold. In addition, STG composite scaffolds show great potential in the wound healing model to enhance rapid epithelialization and tissue granulation.

Amelioration of experimental tendinopathy by lentiviral CD44 gene therapy targeting senescence-associated secretory phenotypes.

CD44 exerts anti-senescence effects in many disease models. We examined senescence in tendinopathy and the effect of CD44 on senescence-associated secretory phenotypes (SASPs). Senescent markers were determined in human tendinopathic long head of bicep (LHB) and normal hamstring tendons. CD44 gene transfer in rat tendinopathic tenocytes stimulated with interleukin (IL)-1ß and a rat Achilles tendinopathy model were performed using lentiviral vectors. Expression levels of p53, p21, and p16 and senescence-associated ß-galactosidase (SA-ß-gal) activity were positively correlated with the severity of human tendinopathy and were higher in rat and human tendinopathic tenocytes than in normal controls. CD44 overexpressed tenocyte transfectants exhibited reduced levels of IL-6, matrix metalloproteinases (MMPs), cyclooxygenase (COX)-2, p53, p21, p16, SA-ß-gal, and phospho-nuclear factor (NF)-κB, whereas their collagen type I alpha 1 (COL1A1) and tenomodulin (tnmd) levels were increased when compared with control transfectants under IL-1ß-stimulated conditions. In the animal model, CD44 overexpression lowered the ultrasound and histology scores and expression levels of the senescent and SASP markers COX-2 and phospho-NF-κB. Bromodeoxyuridine (BrdU)- and tnmd-positive cell numbers were increased in the LVCD44-transduced tendinopathic tendons. Senescence is positively correlated with tendinopathic severity, and CD44 overexpression may protect the tendinopathic tendons from SASPs via anti-inflammation and maintenance of extracellular matrix homeostasis.

The Correlation of Carpal Tunnel Pressure with Clinical Outcomes following Ultrasonographically-Guided Percutaneous Carpal Tunnel Release.

Background: To evaluate the correlation between carpal tunnel pressure (CTP) and the clinical presentations, and to explore the possible predictors for the postoperative recovery pattern in patients with carpal tunnel syndrome (CTS). Materials and Methods: Consecutive patients with idiopathic CTS following percutaneous ultrasound-guided carpal tunnel release (UCTR) were enrolled. CTP was measured preoperatively and immediately after operation. The Boston Carpal Tunnel Questionnaire (BCTQ) and the cross-sectional area (CSA) of median nerve were recorded preoperatively and at 1, 3, and 12 months postoperatively. Results: 37 patients (37 hands; 8 men and 29 females; median age, 59.0 years) were enrolled. CTP significantly decreased immediately from 40.0 (28.0−58.0) to 13.0 (8.0−20.0) mmHg after UCTR. BCTQ scores significantly improved at 1 month postoperatively, and the improvement trend persisted until 12 months postoperatively (p < 0.001). Preoperative CTP was positively correlated with preoperative CSA and preoperative BCTQ scores (p < 0.05, all). Using group-based trajectory modeling, all patients were categorized into the "gradual recovery" or "fast recovery" group. Higher preoperative CTP was significantly associated with a faster recovery pattern (odds ratio: 1.32). Conclusions: Preoperative CTP was well correlated with the clinical presentations and might be a useful predictor for the postoperative clinical recovery pattern.

MicroRNA-133 suppresses cell viability and migration of rheumatoid arthritis fibroblast-like synoviocytes by down-regulation of MET, EGFR, and FSCN1 expression.

Aberrant proliferation and migration of fibroblast-like synoviocytes (FLS) are major characteristics of rheumatoid arthritis (RA). MicroRNA-133 (miR-133) is a tumor-suppressive miRNA that targets various genes responsive for cell proliferation and migration. The aim of this study was to examine the effect of miR-133 on RA FLS. A high throughput miRNA microarray was performed in synovium from mice with collagen-induced arthritis (CIA). Expression levels of miR-133 and the putative targets were determined in synovium and FLS from patients with RA and mice with CIA. Overexpression of miR-133 in RA FLS was performed by lentiviral vector-mediated transfer of precursor miRNA (pre-miR). The expression of miR-133a/b was decreased in the joint tissue and FLS of CIA mice, as determined by miRNA array and qRT-PCR. Down-regulation of miR-133a/b expression could also be observed in synovium and FLS from patients with RA. Overexpression of miR-133 reduced cell viability and migration of RA FLS, with decreased levels of FSCN1, EGFR, and MET. Our findings demonstrated the inhibitory effects of miR-133 on FLS viability and migration, and might contribute to the pharmacologic development of miR-133 therapeutics in patients with RA.

Externally applied force helps reduce bowstring effect of flexors in patients with carpal tunnel release surgery.

BACKGROUND: Patients with severe carpal tunnel syndrome (CTS) undergo carpal tunnel release (CTR) surgery to alleviate pressure in the carpal tunnel. However, the subsequent lack of the transverse carpal ligament (TCL) causes the bowstring phenomenon of the flexor tendons and increases the potential incidence of trigger finger. OBJECTIVE: This study aimed to investigate the effects of various compressive forces on the flexor tendon and identify the appropriate force needed to mitigate the bowstring effect of those flexors. DESIGN: Cross-sectional repeated measures comparison. METHOD: Thirteen CTS patients who underwent CTR surgery were asked to flex the middle finger while applying different external compressive forces, just contact, 4N, and 8N force, over the carpal tunnel. Images of the flexor tendon within the carpal tunnel and at the metacarpal phalangeal (MCP) joint were recorded via ultrasound. RESULT: Results show that the compression force limited the volar migration of the flexor tendon under maximal voluntary contraction (MVC) conditions. Entrance angles between the flexor tendon and metacarpal bone also decreased as the external compressive force increased. CONCLUSIONS: Findings of this study may indicate that applying compression force on the carpal tunnel is useful for CTS patients and can inhibit the volar shift of the flexor digitorum superficialis (FDS) tendon after surgery, which may further prevent trigger finger.