Field-Programmable Gate Array-Based Implementation of Zero-Trust Stream Data Encryption for Enabling 6G-Narrowband Internet of Things Massive Device Access.

With the advent of 6G Narrowband IoT (NB-IoT) technology, IoT security faces inevitable challenges due to the application requirements of Massive Machine-Type Communications (mMTCs). In response, a 6G base station (gNB) and User Equipment (UE) necessitate increased capacities to handle a larger number of connections while maintaining reasonable performance during operations. To address this developmental trend and overcome associated technological hurdles, this paper proposes a hardware-accelerated and software co-designed mechanism to support streaming data transmissions and secure zero-trust inter-endpoint communications. The proposed implementations aim to offload processing efforts from micro-processors and enhance global system operation performance by hardware and software co-design in endpoint communications. Experimental results demonstrate that the proposed secure mechanism based on the use of non-repeating keys and implemented in FPGA, can save 85.61%, 99.71%, and 95.68% of the micro-processor's processing time in key block generations, non-repeating checks, and data block transfers, respectively.

On-site Ultrasound Screens out Asymptomatic Knee Lesions in Elite Adolescent Male Basketball Players.

Basketball is a popular sport worldwide with a high injury risk. In this study, we conducted survey composed of clinical symptom reporting scale, physical examination and meticulous portable musculoskeletal ultrasound to 19 elite male high school basketball players and 15 regular male high school students. Our study showed the incidence of ultrasonographic findings of any lesion, suprapatellar effusion and proximal patellar tendinopathy is significantly higher in player group, and the incidence of asymptomatic ultrasonographic lesion is also higher in player group. Screening for asymptomatic lesions bares clinical relevance and plays a role in prevention of symptom development. With the concise and easy-to-perform ultrasonography protocol we performed and being interpreted by sports team physician, the protocol can offer precise diagnosis of common injury and screening for asymptomatic lesion potentially progressive.

Automatic Key Update Mechanism for Lightweight M2M Communication and Enhancement of IoT Security: A Case Study of CoAP Using Libcoap Library.

The ecosystem for an Internet of Things (IoT) generally comprises endpoint clients, network devices, and cloud servers. Thus, data transfers within the network present multiple security concerns. The recent boom in IoT applications has accelerated the need for a network infrastructure that provides timely and safe information exchange services. A shortcoming of many existing networks is the use of static key authentication. To enable the use of automatic key update mechanisms in IoT devices and enhance security in lightweight machine-to-machine (M2M) communications, we propose a key update mechanism, namely, double OTP (D-OTP), which combines both one-time password (OTP) and one-time pad to achieve an IoT ecosystem with theoretically unbreakable security. The proposed D-OTP was implemented into the Constrained Application Protocol (CoAP) through the commonly used libcoap library. The experimental results revealed that an additional 8.93% latency overhead was required to obtain an unbreakable guarantee of data transfers in 100 CoAP communication sessions.

Simvastatin Downregulates Cofilin and Stathmin to Inhibit Skeletal Muscle Cells Migration.

Statins are the most effective therapeutic agents for reducing cholesterol synthesis. Given their widespread use, many adverse effects from statins have been reported; of these, musculoskeletal complications occurred in 15% of patients after receiving statins for 6 months, and simvastatin was the most commonly administered statin among these cases. This study investigated the negative effects of simvastatin on skeletal muscle cells. We performed RNA sequencing analysis to determine gene expression in simvastatin-treated cells. Cell proliferation and migration were examined through cell cycle analysis and the transwell filter migration assay, respectively. Cytoskeleton rearrangement was examined through F-actin and tubulin staining. Western blot analysis was performed to determine the expression of cell cycle-regulated and cytoskeleton-related proteins. Transfection of small interfering RNAs (siRNAs) was performed to validate the role of cofilin and stathmin in the simvastatin-mediated inhibition of cell migration. The results revealed that simvastatin inhibited the proliferation and migration of skeletal muscle cells and affected the rearrangement of F-actin and tubulin. Simvastatin reduced the expression of cofilin and stathmin. The knockdown of both cofilin and stathmin by specific siRNA synergistically impaired cell migration. In conclusion, our results indicated that simvastatin inhibited skeletal muscle cell migration by reducing the expressions of cofilin and stathmin.

Lidocaine Inhibited Tendon Cell Proliferation and Extracellular Matrix Production by Down Regulation of Cyclin A, CDK2, Type I and Type III Collagen Expression.

Lidocaine injection is a common treatment for tendon injuries. However, the evidence suggests that lidocaine is toxic to tendon cells. This study investigated the effects of lidocaine on cultured tendon cells, focusing on the molecular mechanisms underlying cell proliferation and extracellular matrix (ECM) production. Tendon cells cultured from rat Achilles tendons were treated with 0.5, 1.0, or 1.5 mg/mL lidocaine for 24 h. Cell proliferation was evaluated by Cell Counting Kit 8 (CCK-8) assay and bromodeoxyuridine (BrdU) assay. Cell apoptosis was assessed by Annexin V and propidium iodide (PI) stain. Cell cycle progression and cell mitosis were assessed through flow cytometry and immunofluorescence staining, respectively. The expression of cyclin E, cyclin A, cyclin-dependent kinase 2 (CDK2), p21, p27, p53, matrix metalloproteinases-2 (MMP-2), matrix metalloproteinases-9 (MMP-9), type I collagen, and type III collagen were examined through Western blotting, and the enzymatic activity of MMP-9 was determined through gelatin zymography. Lidocaine reduced cell proliferation and reduced G1/S transition and cell mitosis. Lidocaine did not have a significant negative effect on cell apoptosis. Lidocaine significantly inhibited cyclin A and CDK2 expression but promoted p21, p27, and p53 expression. Furthermore, the expression of MMP-2 and MMP-9 increased, whereas that of type I and type III collagen decreased. Lidocaine also increased the enzymatic activity of MMP-9. Our findings support the premise that lidocaine inhibits tendon cell proliferation by changing the expression of cell-cycle-related proteins and reduces ECM production by altering levels of MMPs and collagens.

Platelet rich plasma releasate promotes proliferation of skeletal muscle cells in association with upregulation of PCNA, cyclins and cyclin dependent kinases.

Platelet rich plasma (PRP) contains various cytokines and growth factors which may be beneficial to the healing process of injured muscle. The purpose of this study is to investigate the effect and molecular mechanism of PRP releasate on proliferation of skeletal muscle cells. Skeletal muscle cells intrinsic to Sprague-Dawley rats were treated with PRP releasate. Cell proliferation was evaluated by 3-[4,5-Dimethylthiazol- 2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay and immunocytochemistry with Ki-67 stain. Flow cytometric analysis was used to evaluate the cell cycle progression. Western blot analysis was used to evaluate the protein expressions of PCNA, cyclin E1, cyclin A2, cyclin B1, cyclin dependent kinase (cdk)1 and cdk2. The results revealed that PRP releasate enhanced proliferation of skeletal muscle cells by shifting cells from G1 phase to S phase and G2/M phases. Ki-67 stain revealed the increase of proliferative capability after PRP releasate treatment. Protein expressions including cyclin A2, cyclin B1, cdk1, cdk2 and PCNA were up-regulated by PRP releasate in a dose-dependent manner. It was concluded that PRP releasate promoted proliferation of skeletal muscle cells in association with the up-regulated protein expressions of PCNA, cyclin A2, cyclin B1, cdk1 and cdk2.

Comparative Effectiveness of Nonoperative Treatments for Chronic Calcific Tendinitis of the Shoulder: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: To investigate the effectiveness of various nonoperative treatments for chronic calcific tendinitis of the shoulder, a systematic review and network meta-analysis of randomized trials was performed to evaluate changes in pain reduction, functional improvements in patients with calcific tendinitis, and the ratio of complete resolution of calcific deposition. DATA SOURCES: Studies were comprehensively searched, without language restrictions, on PubMed, Embase, Cochrane Controlled Trials Register, the Cochrane, and other databases. The reference lists of articles and reviews were cross-checked for possible studies. STUDY SELECTION: Randomized controlled trials from before August 2016 were included. Study selection was conducted by 2 reviewers independently. DATA EXTRACTION: The quality of studies was assessed and data extracted by 2 independent reviewers. Disagreements were settled by consulting a third reviewer to reach a consensus. DATA SYNTHESIS: Fourteen studies with 1105 participants were included in the network meta-analysis that used a random-effect model to investigate the mean difference of pooled effect sizes of the visual analog scale, Constant-Murley score, and the ratio of complete resolution of calcific deposition on native radiographs. CONCLUSIONS: The present network meta-analysis demonstrates that ultrasound-guided needling (UGN), radial extracorporeal shockwave therapy (RSW), and high-energy focused extracorporeal shockwave therapy (H-FSW) alleviate pain and achieve complete resolution of calcium deposition. Compared with low-energy focused extracorporeal shockwave therapy, transcutaneous electrical nerve stimulation, and ultrasound therapy, H-FSW is the best therapy for providing functional recovery. Physicians should consider UGN, RSW, and H-FSW as alternative effective therapies for chronic calcific tendinitis of the shoulder when initial conservative treatment fails.

Low-level laser irradiation stimulates tenocyte proliferation in association with increased NO synthesis and upregulation of PCNA and cyclins.

Low-level laser therapy is commonly used to treat tendinopathy or tendon injury. Tendon healing requires tenocyte migration to the repair site, followed by proliferation and synthesis of the extracellular matrix. There are few evidence to elucidate that low-level laser promote tenocyte proliferation. This study was designed to determine the effect of laser on tenocyte proliferation. Furthermore, the association of this effect with secretion of nitric oxide (NO) and the expressions of proliferating cell nuclear antigen (PCNA) and cyclins D1, E, A, and B1 was investigated. Tenocytes intrinsic to rat Achilles tendon were treated with low-level laser (660 nm). Tenocyte proliferation was evaluated by MTT assay and immunocytochemistry with Ki-67 stain. NO in the conditioned medium was measured by ELISA. Western blot analysis was used to evaluate the protein expressions of PCNA and cyclins D1, E, A, and B1. The results revealed that tenocytes proliferation was enhanced dose dependently by laser. NO secretion was increased after laser treatment. PCNA and cyclins E, A, and B1 were upregulated by laser. In conclusion, low-level laser irradiation stimulates tenocyte proliferation in a process that is mediated by upregulation of NO, PCNA, and cyclins E, A, and B1.

Pentadecapeptide BPC 157 enhances the growth hormone receptor expression in tendon fibroblasts.

BPC 157, a pentadecapeptide derived from human gastric juice, has been demonstrated to promote the healing of different tissues, including skin, muscle, bone, ligament and tendon in many animal studies. However, the underlying mechanism has not been fully clarified. The present study aimed to explore the effect of BPC 157 on tendon fibroblasts isolated from Achilles tendon of male Sprague-Dawley rat. From the result of cDNA microarray analysis, growth hormone receptor was revealed as one of the most abundantly up-regulated genes in tendon fibroblasts by BPC 157. BPC 157 dose- and time-dependently increased the expression of growth hormone receptor in tendon fibroblasts at both the mRNA and protein levels as measured by RT/real-time PCR and Western blot, respectively. The addition of growth hormone to BPC 157-treated tendon fibroblasts dose- and time-dependently increased the cell proliferation as determined by MTT assay and PCNA expression by RT/real-time PCR. Janus kinase 2, the downstream signal pathway of growth hormone receptor, was activated time-dependently by stimulating the BPC 157-treated tendon fibroblasts with growth hormone. In conclusion, the BPC 157-induced increase of growth hormone receptor in tendon fibroblasts may potentiate the proliferation-promoting effect of growth hormone and contribute to the healing of tendon.

Lidocaine inhibits migration of tenocytes by downregulating focal adhesion kinase and paxillin phosphorylation.

Lidocaine is the most frequently applied local infiltration anesthetic agent for treating tendinopathies. However, studies have discovered lidocaine to negatively affect tendon healing. In the current study, the molecular mechanisms and effects of lidocaine on tenocyte migration were evaluated. We treated tenocytes intrinsic to the Achilles tendons of Sprague-Dawley rats with lidocaine. The migration ability of cells was analyzed using electric cell-substrate impedance sensing (ECIS) and scratch wound assay. We then used a microscope to evaluate the cell spread. We assessed filamentous actin (F-actin) cytoskeleton formation through immunofluorescence staining. In addition, we used Western blot analysis to analyze the expression of phospho-focal adhesion kinase (FAK), FAK, phospho-paxillin, paxillin, and F-actin. We discovered that lidocaine had an inhibitory effect on the migration of tenocytes in the scratch wound assay and on the ECIS chip. Lidocaine treatment suppressed cell spreading and changed the cell morphology and F-actin distribution. Lidocaine reduced F-actin formation in the tenocyte during cell spreading; furthermore, it inhibited phospho-FAK, F-actin, and phospho-paxillin expression in the tenocytes. Our study revealed that lidocaine inhibits the spread and migration of tenocytes. The molecular mechanism potentially underlying this effect is downregulation of F-actin, phospho-FAK, and phospho-paxillin expression when cells are treated with lidocaine.

Leukocyte-poor platelet-rich plasma and leukocyte-rich platelet-rich plasma promote myoblast proliferation through the upregulation of cyclin A, cdk1, and cdk2.

Muscle injuries are common among athletes and often treated with platelet-rich plasma (PRP). However, whether the leukocyte concentration affects the efficacy of PRP in treating muscle injuries remains unclear. This study investigated the effects of leukocyte-poor platelet-rich plasma (LP-PRP) and leukocyte-rich platelet-rich plasma (LR-PRP) on myoblast proliferation and the molecular mechanisms underlying these effects. Myoblasts were treated with 0.5% LP-PRP, 0.5% LR-PRP, 1% LP-PRP, or 1% LR-PRP for 24 h. The gene expression of the LP-PRP- and LR-PRP-treated myoblasts was determined using RNA sequencing analysis. Cell proliferation was evaluated using an bromodeoxyuridine (BrdU) assay, and cell cycle progression was assessed through flow cytometry. The expression of cyclin A, cyclin-dependent kinase 1 (cdk1), and cdk2 was examined using Western blotting. The expression of myoblast determination protein 1 (MyoD1) was examined through Western blotting and immunofluorescence staining. The LP-PRP and LR-PRP both promoted the proliferation of myoblasts and increased differential gene expression of myoblasts. Moreover, the LP-PRP and LR-PRP substantially upregulated the expression of cyclin A, cdk1, and cdk2. MyoD1 expression was induced in the LP-PRP and LR-PRP-treated myoblasts. Our results corroborate the finding that LP-PRP and LR-PRP have similar positive effects on myoblast proliferation and MyoD1 expression.

Aging is associated with increased activities of matrix metalloproteinase-2 and -9 in tenocytes.

BACKGROUND: Most tendon pathology is associated with degeneration, which is thought to involve cyclic loading and cumulative age-related changes in tissue architecture. However, the association between aging and degeneration of the extracellular matrix (ECM) in tendons has not been investigated extensively. METHODS: We examined tenocytes from Achilles tendons taken from rats of three different ages (2, 12, and 24 months). Tenocyte viability was assessed using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. Quantitative real-time polymerase chain reaction (PCR) was used to determine the levels of mRNAs that encode type-I collagen, matrix metalloproteinase (MMP)-2 and -9, tissue inhibitor of metalloproteinase (TIMP)-1 and -2 and transforming growth factor (TGF)-ß1. Gelatin zymography was used to evaluate the enzymatic activities of MMP-2 and -9. Furthermore, the concentration of TGF-ß1 in conditioned medium was evaluated using enzyme-linked immunosorbent assay (ELISA). RESULTS: The results of the MTT assay showed that the number of viable tenocytes decreased with age. No differences were observed in the levels of mRNAs that encode type-I collagen and TGF-ß1 among the three age groups, and the TGF-ß1 concentration did not change with age. However, mRNAs that encode MMP-2 and -9 were significantly more abundant in tenocytes from the aging group, and gelatin zymography revealed that the enzymatic activities of MMP-2 and -9 also increased significantly with age. Furthermore, as compared with young group, mRNAs that encode TIMP-1 and -2 were significantly decreased in tenocytes from the aging group. CONCLUSIONS: Activities of MMP-2 and MMP-9 in tenocytes increase with age. This might provide a mechanistic explanation of how aging contributes to tendinopathy or tendon rupture with age.

High glucose concentration up-regulates the expression of matrix metalloproteinase-9 and -13 in tendon cells.

BACKGROUND: Diabetes mellitus is associated with tendinopathy or tendon injuries. However, the mechanism underlying diabetic tendinopathy is unclear. The purpose of this study was to examine the effects of high glucose concentrations on the activity and expression of matrix metalloproteinases, type I collagen, and type III collagen in tendon cells. METHODS: Tendon cells from rat Achilles tendons were treated with 6 mM, 12 mM, and 25 mM glucose, and then cell proliferation was evaluated by the 3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. Messenger RNA (mRNA) expression of MMP-2, MMP-8, MMP-9, and MMP-13 and type I and type III collagen was assessed by quantitative real-time polymerase chain reaction (PCR). The enzymatic activity of MMP-2 and MMP-9 was measured by gelatin zymography. RESULTS: The MTT assay results showed that the glucose concentration did not affect tendon cell proliferation. The results of the real-time PCR assay revealed that the mRNA expression of MMP-9 and MMP-13 was up-regulated by treatment with 25 mM glucose, whereas the mRNA expression of type I and III collagen was not affected. Gelatin zymography showed that 25 mM glucose increased the enzymatic activity of MMP-9. CONCLUSIONS: High glucose concentration up-regulates the expression of MMP-9 and MMP-13 in tendon cells, which may account for the molecular mechanisms underlying diabetic tendinopathy.

Quantification of skeletal muscle fibrosis at different healing stages using sonography: a morphologic and histologic study in an animal model.

OBJECTIVES: This study attempted to quantify the degree of muscle fibrosis on sonograms of injured gastrocnemius muscles at different healing stages in a rat model. Correlations between the quantifications and histologic assessments of the injured muscles were also determined. METHODS: Sonograms and histologic findings of gastrocnemius muscle fibrosis were obtained during the second, third, and fourth weeks after surgically induced lesions in the right gastrocnemius muscles of 15 Wistar rats. The echo intensity, reflecting the degree of brightness on a sonogram, was divided into 256 gray levels instead of decibels. The mean echo intensity of each pixel in the region of interest was calculated as a summation of the echo intensities in all pixels divided by the pixel numbers in the region. To control individual variations among the rats, we calculated a K value, defined as the difference in the mean echo intensity between normal and affected muscles. RESULTS: Significant correlations (r > 0.7; P < .05) between mean echo intensity and K values and the fibrous tissue percentage were identified. The mean echo intensity in the injured gastrocnemius muscles was significantly (P = .029) greater than that in the normal muscles 3 weeks after injury. In histologic assessments, muscle fibrosis was most prominent 3 weeks after injury. However, the differences in fibrosis at different healing stages were not significant. CONCLUSIONS: Mean echo intensity and K values can reflect the extent of fibrosis in affected muscles and may be valuable for quantifying muscle fibrosis in clinical practice.

Reproducibility of sonographic measurement of thickness and echogenicity of the plantar fascia.

BACKGROUND: To evaluate the intra- and interrater reliability of ultrasonographic measurements of the thickness and echogenicity of the plantar fascia. METHODS: Eleven patients (20 feet), who complained of inferior heel pain, and 26 volunteers (52 feet) were enrolled. Two sonographers independently imaged the plantar fascia in both longitudinal and transverse planes. Volunteers were assessed twice to evaluate intrarater reliability. Quantitative evaluation of the echogenicity of the plantar fascia was performed by measuring the mean gray level of the region of interest using Digital Imaging and Communications in Medicine viewer software. RESULTS: Sonographic evaluation of the thickness of the plantar fascia showed high reliability. Sonographic evaluations of the presence or absence of hypoechoic change in the plantar fascia showed surprisingly low agreement. The reliability of gray-scale evaluations appears to be much better than subjective judgments in the evaluation of echogenicity. Transverse scanning did not show any advantage in sonographic evaluation of the plantar fascia. CONCLUSIONS: The reliability of sonographic examination of the thickness of the plantar fascia is high. Mean gray-level analysis of quantitative sonography can be used for the evaluation of echogenicity, which could reduce discrepancies in the interpretation of echogenicity by different sonographers. Longitudinal instead of transverse scanning is recommended for imaging the plantar fascia.

The effects of aging on quantitative sonographic features of rotator cuff tendons.

PURPOSE: Grayscale analysis is a practical, objective, and easy way to quantify echogenicity during ultrasonography. The purpose of the current study was to measure the changes in thickness and echogenicity that result from aging of the rotator cuff and long head of the biceps tendons. METHODS: The study comprised 45 volunteers, aged between 20 and 84 years and without history of shoulder pain. Participants were divided into three groups: young, middle-aged, and old. All subjects underwent standard ultrasonography of both shoulders. Tendon thickness and tear were recorded, and images in both transverse and longitudinal scans were taken for grayscale analysis. To reduce the attenuation effect from skin and subcutaneous fat, we used the ratio of echogenicity of the tendon to that of the reference muscle and compared the tendon echogenicity among the different age groups. Sonographic findings were also correlated with age. RESULTS: The supraspinatus tendon was significantly thicker in elderly participants and this was positively correlated with age. Moreover, the echogenicity ratio of the supraspinatus tendon decreased in the elderly group and showed a negative correlation with age. There was a higher prevalence of supraspinatus tendon tears in the older participants. CONCLUSIONS: Our results indicate that supraspinatus tendons became thickened, hypoechogenic, and more likely to tear with age. The study presents a simple and useful method to investigate the echogenicity of the rotator cuff quantitatively.

Anticipative QoS Control: A Self-Reconfigurable On-Chip Communication.

A self-reconfigurable Network-on-Chip (NoC) architecture that supports anticipative Quality of Service (QoS) control with penetrative switch ability is proposed to enhance the performance of bidirectional-channel NoC communication while supporting prioritized packet transmission services. The anticipative QoS control not only allows each communication channel to be dynamically self-configured to transmit flits in either direction for a better channel utilization of on-chip hardware resources, but also enhances the latency performance for QoS services. The proposed anticipative control is based on penetratingly observing channel direction requests of routers that is two hops away from the current one. The added ability enables a router to allocate high-priority packets to a dedicated virtual channel and then rapidly bypass it to the next destination router. The provided flexibility of packet switch promises better channel bandwidth utilization, lower packet delivery latency, and furthermore guarantees the high-priority packets being served with a better QoS. Accordingly, in this paper, an enhanced NoC architecture supporting the hybrid anticipative QoS, penetrative switch, and bidirectional-channel control, namely Anticipative QoS Bidirectional-channel NoC (AQ-BiNoC) is presented. Tested with cycle-accurate synthetic traffic patterns, significant performance enhancement has been observed when the proposed AQ-BiNoC architecture is compared against conventional NoC designs.

Sonographic measurements of the thickness of the soft tissues of the interscapular region in a population of normal young adults.

BACKGROUND: To use sonography (US) to measure the interscapular soft-tissue thickness and to determine any correlation with anthropometric indices. METHODS: Fifty-five healthy young adults (21 men and 34 women) with a mean age of 22.1 ± 3.0 years (range, 18-35) were enrolled. High-resolution US was used to measure the bilateral soft-tissue thickness near the medial border of the scapula. Anthropometric indices, including body weight, height, and circumferences of chest, waist, and hip, were also measured. RESULTS: On the right side, mean values ± standard deviation for the thickness of the trapezius, rhomboid, and posterior serratus muscles in millimeters were 4.9 ± 1.0, 6.3 ± 2.3, and 3.5 ± 1.4, respectively, for men and 3.4 ± 0.8, 3.8 ± 1.7, and 2.2 ± 1.5, respectively, for women. The thickness of each muscle was significantly greater in men than in women (p < 0.05). For both genders, no significant differences in the soft-tissue thicknesses were found between both sides. Based on the anthropometric indices, body weight was the only significant contributor to the soft-tissue thickness. CONCLUSIONS: US is a practical tool for measuring soft-tissue thickness in the interscapular region. Body weight and soft-tissue thickness are closely associated.

Platelet-Rich Plasma Releasate Promotes Early Healing in Tendon After Acute Injury.

BACKGROUND: Acute tendon injury can limit motion and thereby inhibit tendon healing. Positive results have been found after the use of platelet-rich plasma (PRP) to treat tendon injury; however, the early effects of PRP on tendon regeneration are not known. PURPOSE/HYPOTHESIS: The purpose of this study was to evaluate the effects of PRP releasate (PRPr) on the early stages of tendon healing in a rat partial tenotomy model. It was hypothesized that PRPr can promote early healing of an Achilles tendon in rats. STUDY DESIGN: Controlled laboratory study. METHODS: PRP was prepared by a 2-step method of manual platelet concentration from 10 rats. PRPr was isolated from the clotted preparation after activation by thrombin and was applied to an Achilles tendon on 1 side of 30 rats on the second day after partial tenotomy, with normal saline used as the control on the other side. Achilles tendon samples were harvested 5 and 10 days after tenotomy. At each time point, 15 Achilles tendon samples were obtained, of which 5 samples were evaluated by Masson trichrome staining, apoptosis, and cell proliferation, while the other 10 samples were tested for tensile strength using a material testing machine. RESULTS: Compared with saline-treated control tendons, the PRPr-treated tendons showed increased collagen synthesis near the cut edge and fewer apoptotic cells (P = .01). An immunohistochemical analysis revealed more Ki-67-positive cells but fewer cluster of differentiation (CD) 68+ (ED1+) macrophages in PRPr tendons compared with saline-treated tendons (P < .01). Tendons treated with PRPr also showed higher ultimate tensile strength than those treated with saline (P = .03). CONCLUSION: PRPr treatment promotes tissue recovery in the early phase of tendon healing by stimulating tendon cell proliferation and collagen production while inhibiting cell apoptosis and CD68+ (ED1+) macrophage infiltration. CLINICAL RELEVANCE: These findings suggest that with PRPr treatment, higher loads can be applied to the healing tendon at an earlier time, which can help the patient resume activity earlier.

Use of Platelet-Rich Plasma Plus Suramin, an Antifibrotic Agent, to Improve Muscle Healing After Injuries.

BACKGROUND: The increasing use of platelet-rich plasma (PRP) to treat muscle injuries raises concerns because transforming growth factor-beta (TGF-ß) in PRP may promote fibrosis in the injured muscle and thus impair muscle regeneration. PURPOSE: To investigate whether suramin (a TGF-ß inhibitor) can reduce muscle fibrosis to improve healing of the injured muscle after PRP treatment and identify the underlying molecular mechanism. STUDY DESIGN: Controlled laboratory study. METHODS: Myoblasts isolated from the gastrocnemius muscle of Sprague Dawley rats were treated with PRP or PRP plus suramin. MTT assays were performed to evaluate cell viability. The expression of fibrosis-associated proteins (such as type I collagen and fibronectin), Smad2, and phosphorylated Smad2 was determined using Western blot analysis and immunofluorescent staining. An anti-TGF-ß antibody was employed to verify the role of TGF-ß in fibronectin expression. Gastrocnemius muscles were injured through a partial transverse incision and then treated using PRP or PRP plus suramin. Hematoxylin and eosin staining was conducted to evaluate the healing process 7 days after the injury. Immunofluorescent staining was performed to evaluate fibronectin expression. Muscle contractile properties-fast-twitch and tetanic strength-were evaluated through electric stimulation. RESULTS: PRP plus 25 µg/mL of suramin promoted myoblast proliferation. PRP induced fibronectin expression in myoblasts, but suramin reduced this upregulation. The anti-TGF-ß antibody also reduced the upregulation of fibronectin expression in the presence of PRP. The upregulation of phosphorylated Smad2 by PRP was reduced by either the anti-TGF-ß antibody or suramin. In the animal study, no significant difference was discovered in muscle healing between the PRP versus PRP plus suramin groups. However, the PRP plus suramin group had reduced fibronectin expression at the injury site. Fast-twitch strength and tetanic strength were significantly higher in the injured muscle treated using PRP or PRP plus suramin. CONCLUSION: Simultaneous PRP and suramin use reduced fibrosis in the injured muscle and promoted healing without negatively affecting the muscle's contractile properties. The underlying molecular mechanism may be associated with the phosphorylated Smad2 pathway. CLINICAL RELEVANCE: Simultaneous PRP and suramin use may reduce muscle fibrosis without compromising muscle contractile properties and thus improve muscle healing.