Circular RNA circ-NT5C2 acts as a potential novel biomarker for prognosis of osteosarcoma.

We detected some serious inaccuracies and mistakes. Therefore, the article, "Circular RNA circ-NT5C2 acts as a potential novel biomarker for prognosis of osteosarcoma, by W.-B. Nie, L.-M. Zhao, R. Guo, M.-X. Wang, F.-G. Ye, published in Eur Rev Med Pharmacol Sci 2018; 22 (19): 6239-6244-DOI: 10.26355/eurrev_201810_16030-PMID: 30338784" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/16030.

Inhibition of CACNA1H can alleviate endoplasmic reticulum stress and reduce myocardial cell apoptosis caused by myocardial infarction.

OBJECTIVE: In recent years, coronary heart disease (CHD) has become a disease that cannot be ignored by residents of our country, because CHD will not only endanger people's quality of life, but also threaten their lives. Therefore, this research mainly explores the correlation between myocardial infarction (MI) with endoplasmic reticulum (ER) stress and apoptosis. MATERIALS AND METHODS: First, we constructed a model of myocardial ischemia and hypoxia (I/H) in vivo and in vitro, and examined the change of CACNA1H expression. At the same time, in order to research the role of CACNA1H, we chose CACNA1H-specific inhibitor ABT-639 to next research and detect changes in heart injury by detecting changes in creatine kinase (CK) content and lactate dehydrogenase (LDH) activity. Next, we used TUNEL staining and immunofluorescence staining to detect changes in apoptosis and ER stress, and analyzed changes in ER stress and apoptotic pathway expression by Western blotting and quantitative Real-Time Polymerase Chain Reaction (qRT-PCR). RESULTS: At 28 days after MI, the cardiac function of the mice was significantly reduced, the myocardial cell apoptosis rate was dramatically increased, and CACNA1H expression was dramatically increased in vivo and in vitro. In addition, we treated the model group with the ABT-639, and found that ABT-639 can partially protect myocardial function and relieve myocardial cell apoptosis. At the same time, ABT-639 may reduce H9c2 injury after I/H by reducing the degree of ER stress, because we found that the use of ABT-639 can dramatically reduce ER stress-related factors expression, and can inhibit the expression of apoptosis-related factors Caspase-3 and Caspase-9. CONCLUSIONS: The CACNA1H inhibitor ABT-639 can alleviate myocardial cell apoptosis caused by MI by reducing the ER stress response.

MiR-146a-5p inhibits proliferation and promotes apoptosis of oral squamous cell carcinoma cells by regulating NF-κB signaling pathway.

OBJECTIVE: The aim of this study was to investigate the function and potential mechanism of micro ribonucleic acid (miR)-146a-5p in oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS: The expression of miR-146a-5p in OSCC tissues and cell lines was examined by quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR) analysis. Then, the role of miR-146a-5p in proliferation was analyzed by Cell Counting Kit-8 (CCK-8) assay. Besides, the proliferation and apoptosis of OSCC cells were detected by the colony formation assay and flow cytometry, respectively. Finally, the regulatory effect of miR-146a-5p/nuclear factor-kappa B subunit 1 (NF-κB1) was determined by Western blotting assay and Luciferase reporter assay system. RESULTS: The expression of miR-146a-5p was markedly upregulated in OSCC cell lines. In addition, the silence of miR-146a-5p inhibited the proliferation and promoted the apoptosis of OSCC cells. According to the results of the Western blotting analysis and Luciferase reporter gene assay, NF-κB1 was identified as a direct target of miR-146a-5p. Moreover, the downregulation of NF-κB1 restored the inhibitory effect of silenced miR-146a-5p on the proliferation of SCC-9 cells. CONCLUSIONS: MiR-146a-5p can inhibit the proliferation and accelerate the apoptosis of OSCC cells by directly targeting NF-κB1, and it plays a carcinogenic role in OSCC.

MiR-133a alleviates renal injury caused by sepsis by targeting BNIP3L.

OBJECTIVE: Sepsis is an important cause of acute kidney injury (AKI), seriously jeopardizing the health of patients. This paper's aim was to investigate whether microRNA-133a had a protective effect on sepsis-induced kidney injury. MATERIALS AND METHODS: We established a kidney injury model with lipopolysaccharide (LPS) and divided TCMK-1 cells into 4 groups: control group (con); LPS treatment group; LPS + negative control (NC) treatment group; LPS + miR-133a mimic (mim) group. The expressions of miR-133a, TNF-α mRNA, IL-6 mRNA, Bax mRNA, Bcl-2 mRNA, BNIP3L mRNA, IκKα Mrna and IκB-α mRNA were detected by PCR. Western blot was used to detect the protein expression of TNF-α, IL-6, Bax, Bcl-2, BNIP3L, IκKα and IκB-α. Cell viability was measured by cell counting kit-8 (CCK-8). Flow cytometry was utilized to detect apoptosis rate. IL-1ß immunofluorescence and terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) staining were used to observe the inflammation and apoptosis in TCMK-1 cells. RESULTS: The miR-133a expression was decreased in TCMK-1 cells treated with LPS. In the LPS treatment group, the expression of TNF-α, IL-6, Bax, BNIP3L and IκKα increased, and the expression of Bcl-2 and IκB-α decreased. When overexpressing miR-133a, the protein and mRNA expression of TNF-α, IL-6, Bax, BNIP3L and IκKα decreased markedly, while the expression of Bcl-2 and IκB-α increased markedly. Compared with the LPS-treated group, the apoptotic rate, the number of TUNEL-positive cells, and the immunofluorescence intensity of IL-1ß in LPS+mim group were greatly decreased. CONCLUSIONS: The miR-133a expression was decreased in TCMK-1 cells treated by LPS and miR-133a can inhibit inflammation and apoptosis of TCMK-1 cells induced by LPS by targeting BNIP3L via inhibiting NF-κB pathway.

MiR-875 can regulate the proliferation and apoptosis of non-small cell lung cancer cells via targeting SOCS2.

OBJECTIVE: To investigate the effect of miR-875 on the proliferation and apoptosis of non-small cell lung cancer (NSCLC) cancer cell line A549 and the related mechanism. PATIENTS AND METHODS: 30 paired tumor tissue and the adjacent tissue were collected. Real Time-quantitative Polymerase Chain Reaction (RT-qPCR) has been performed to detect the expression of miR-875 in NSCLC tissues and adjacent normal tissues. Moreover, suppressor of cytokine signaling 2 (SOCS2) has been predicted as a target of miR-875, and Dual-Luciferase reporter assay has been performed to confirm the targeting relationship; furthermore, the expression of SOCS2 in tumor tissue and the adjacent tissue were compared. Next, human NSCLC cell line A549 cells were cultured and transfected with miR-875 inhibitor with or without SOCS2 siRNA, and the proliferation and apoptosis of the cells were evaluated by Cell Counting Kit (CCK-8) and flow cytometry methods. Finally, the relative protein expression of Wnt and ß-catenin were analyzed by Western blot analysis. RESULTS: MiR-875 was significantly up-regulated in NSCLC tissues compared with the adjacent tissues. SOCS2 was confirmed as a target of miR-875, and the expression of SOCS2 was markedly decreased in NSCLC tissues. Moreover, the knockdown of miR-875 inhibited the proliferation and promoted the apoptosis of A549 cells, while transfection of SOCS2 siRNA can block miR-875 inhibitor-induced anti-proliferative effects. Finally, the transfection of miR-875 inhibitor decreased the expression of Wnt and ß-catenin, and SOCS2 siRNA can reverse the effect. CONCLUSIONS: MiR-875 may regulate the proliferation and apoptosis of NSCLC cells via targeting SOCS2, suggesting that miR-875 has the potential to become a therapeutic target for the treatment in NSCLC.

Nicotinamide protects chronic hypoxic myocardial cells through regulating mTOR pathway and inducing autophagy.

OBJECTIVE: To determine the protective effect of nicotinamide on chronic hypoxic myocardial cells and its underlying mechanism. MATERIALS AND METHODS: The H9C2 cell lines were taken as objects of study, and were divided into blank group, hypoxia group and nicotinamide treatment group. The cell viability, apoptosis level, autophagy level and mammalian target of rapamycin (mTOR) pathway activity in each group were detected via Cell Counting Kit-8 (CCK8) assay, Hoechst staining, immunofluorescence staining, Polymerase Chain Reaction (PCR) and Western blotting, respectively. RESULTS: Nicotinamide could protect the viability of normoxic and chronic hypoxic myocardial cells. Besides, it could also inhibit the expression of caspase3 messenger ribonucleic acid (mRNA) in chronic hypoxic myocardial cells, and reduce the expression of apoptosis-related proteins. Furthermore, it could induce the mRNA expression of autophagy-associated gene 5 (ATG5) and increase the expression of autophagy-related proteins. Further study on the mechanism of nicotinamide showed that nicotinamide could inhibit the activity of the mTOR pathway, thus regulating the autophagy. CONCLUSIONS: Nicotinamide induces the autophagy of chronic hypoxic myocardial cells by regulating the mTOR pathway, thereby protecting cells from apoptosis.

LncRNAp21 promotes osteogenic differentiation of mesenchymal stem cells in the rat model of osteoporosis by the Wnt/ß-catenin signaling pathway.

OBJECTIVE: The aim of this study was to explore the promoting effect of long non-coding ribonucleic acid p21 (lncRNAp21) on the osteogenic differentiation of mesenchymal stem cells in the rat model of osteoporosis (OP) through the Wnt/ß-catenin signaling pathway. MATERIALS AND METHODS: A total of 30 healthy female rats were selected and randomly divided into three groups, including the lncRNAp21 group, OP model group (model group) and normal group. Rats in the lncRNAp21 group were given a certain quantity of lncRNAp21 inhibitors for gavage. Rats in the model group were regularly given 0.9% NaCl for gavage every day after the removal of bilateral ovaries. Meanwhile, rats in the normal group were fed normally without any changes. Bone mineral density (BMD) was measured after 12 weeks of modeling. The levels of procollagen type I N-terminal propeptide (PINP), serum estradiol (E2), osteocalcin (OC), bone alkaline phosphatase (BALP), C-terminal cross-linking telopeptide of type I collagen (CTX) and tartrate-resistant acid phosphatase 5b (TRACP-5b) in the bone and serum of rats were measured by enzyme-linked immunosorbent assay (ELISA). Besides, quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) and Western blotting were adopted to detect the mRNA and protein expressions of Wnt1 and ß-catenin in bone tissues, respectively. RESULTS: Compared with the normal group and lncRNAp21 group, the serum level of E2 in the model group decreased significantly (p<0.05). BMD and phosphorus (P) content in the model group were both markedly lower than those of the normal group and lncRNAp21 group. However, calcium (Ca) content was remarkably higher than that of the normal group and lncRNAp21 group (p<0.05). The serum levels of bone resorption markers (including TRACP-5b and CTX) in the model group were prominently higher than those of the normal group (p<0.05). However, the levels of the two markers in the lncRNAp21 group were significantly lower than the model group (p<0.05). Additionally, bone formation markers (including OC, PINP and BALP) in the serum of rats in the model group were notably higher than those in the normal group and lncRNAp21 group (p<0.05). QRT-PCR and Western blotting results revealed that the mRNA and protein expressions of Wnt1 and ß-catenin in bone tissues of the model group were markedly lower than those of the normal group. However, the mRNA and protein expressions of Wnt1 and ß-catenin in the lncRNAp21 group were remarkably higher than the model group (p<0.05). CONCLUSIONS: Low expression of lncRNAp21 activates the Wnt/ß-catenin signaling pathway by increasing E2 secretion, eventually stimulating bone formation and increasing osteogenic differentiation of mesenchymal stem cells in OP model rats.

MiRNA-210 induces the apoptosis of neuronal cells of rats with cerebral ischemia through activating HIF-1α-VEGF pathway.

OBJECTIVE: This study aims to explore the expression of micro-ribonucleic acid (miRNA)-210 in the cerebral cortex of rat model with global cerebral ischemia, and determine its function on the regulation of the apoptosis of neuronal cells. MATERIALS AND METHODS: Rat models of global cerebral ischemia were established in vitro. Rats were euthanized at 24 h after reperfusion and the cerebral cortex was collected. The expression of miRNA-210 was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Neuronal cells were transfected by liposomes in vitro and cells were divided into neuronal cell group (group i), neuronal cell + miRNA-210 mimic group (group ii) and neuronal cell + miRNA-210 inhibitor group (group iii). The cell apoptosis rate and gene and protein expressions of HIF-1α, VEGF and Caspase-3 were measured. RESULTS: The level of miRNA-210 in rats with global cerebral ischemia was remarkably higher than that in rats from sham operation group (p<0.05). The apoptosis rate of neuronal cells was increased evidently when miRNA-210 was overexpressed, and the expressions of HIF-1α, VEGF and Caspase-3 were elevated markedly at both mRNA and protein levels. CONCLUSIONS: Our data indicate that miRNA-210 expression is upregulated in the rats with global cerebral ischemia, and the rise of miRNA-210 level increases the apoptosis of neuronal cells through the activation of HIF-1α-VEGF signaling pathway.

MiR-21 regulates proliferation and apoptosis of oral cancer cells through TNF-α.

OBJECTIVE: MicroRNA (miRNA) can widely regulate gene expression. More importantly, various miRNA molecules have been found with regulatory functions for tumor cell proliferation or apoptosis. The study showed that miR-21 inhibited apoptosis of cultured cancer cells, whilst tumor necrosis factor α (TNF-α) plays important roles in the proliferation of tumor cells. This study manipulated miR-21 expression in cultured oral cancer cells and aimed to investigate its effects on TNF-α expression, and on proliferation or apoptosis of cancer cells. MATERIALS AND METHODS: Specific agonist and antagonist were synthesized based on miR-21 sequence. In vitro cultured oral cancer cell line, SCC-15 was transfected with agonist or antagonist, in parallel with normal cultured cells as negative control group. Quantitative Real-time PCR (qRT-PCR) was used to measure mRNA expression of miR-21 and TNF-α in transfected cells. Western blot was used for measuring TNF-α expression, and 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) or Hoechst-33342 staining was used to measure proliferation and apoptosis of SCC-15 cells. RESULTS: MiR-21 expression was potentiated or depressed with transfection of agonist or antagonist, respectively, illustrating the effectiveness of synthesized sequence in cultured SCC-15 cells. Moreover, TNF-α expression was positively correlated with miR-21, TNF-α up-regulation significantly potentiated the proliferation potency of SCC-15 cells, and TNF-α down-regulation remarkably weakened proliferation potency (p<0.05). The TNF-α expression did not affect apoptosis of SCC-15 cells (p>0.05 compared to the control group). CONCLUSIONS: MiR-21 could participate in the proliferation of cultured SCC-15 cells via targeting TNF-α expression, but without any significant effects on cell apoptosis.

HOTAIR promotes inflammatory response after acute myocardium infarction by upregulating RAGE.

OBJECTIVE: The aim of this study was to explore the role of HOTAIR in inflammatory response after acute myocardium infarction (AMI) and to investigate its underlying mechanism. MATERIALS AND METHODS: The AMI model was first constructed in rats, and heart tissues were harvested. Expression levels of HOTAIR and receptor of advanced glycation end-products (RAGE) in rat heart were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The protein expression level of pEKR in rat heart was detected by Western blot. The levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in rats were determined by enzyme-linked immunosorbent assay (ELISA). The hypoxia-induced H9C2 cells were used to construct the MI model in vitro. Meanwhile, the expression levels of HOTAIR and RAGE in H9C2 cells were detected. The levels of TNF-α and IL-6 in the culture medium were determined by ELISA. Rescue experiments were conducted by co-transfecting pcDNA-HOTAIR and si-RAGE in H9C2 cells. Subsequently, the levels of pERK, TNF-α, and IL-6 were detected. RESULTS: The mRNA expression levels of HOTAIR and RAGE in the AMI group were significantly higher than those of the control group. Western blot showed remarkably higher protein levels of RAGE and pERK in AMI rats when compared with those of controls. Similarly, results of ELISA indicated that the levels of TNF-α and IL-6 in AMI rats were significantly higher than those of controls. Meanwhile, overexpression of HOTAIR in H9C2 cells remarkably elevated the expression levels of HOTAIR and RAGE. In addition, upregulated pERK, TNF-α, and IL-6 were observed in H9C2 cells overexpressing HOTAIR, which could be reversed by RAGE knockdown. CONCLUSIONS: HOTAIR promotes inflammatory response after AMI by upregulating RAGE expression.

Research on mechanism of PCS in damaging vascular endothelial cells and promoting formation of atherosclerosis via TLR4/TREM-1.

OBJECTIVE: The study aimed to explore the effects of p-cresyl sulfate (PCS) of damaging vascular endothelial cells and promoting the formation of atherosclerosis in mice. MATERIALS AND METHODS: The apolipoprotein E (ApoE)-/- mice were fed normally and with a high-fat diet; the ApoE-/- mice fed with high-fat diet were divided into two groups and treated with blank control and PCS, respectively. The aortic arch in each group was taken and underwent the oil red O staining, and the serum PCS content in each group was detected. The basic components of plaque were observed, including foam cells, lipid deposition, and cholesterol crystal. Moreover, human umbilical vein endothelial cells were cultured and divided into control group, PCS treatment group (PCS), PCS treatment with TLR4 overexpression group (PCS+TLR4+), and PCS treatment with TLR4 knock-out group (PCS+TLR4-). The degree of endothelial cell damage was detected using a cluster of differentiation CD42b-/CD31+ endothelial microparticles (EMPs), and expressions of Toll-like receptor 4 (TLR4), triggering receptor expressed on myeloid cells-1 (TREM-1), phosphorylated-endothelial nitric oxide synthase (p-eNOS), and tumor necrosis factor-α (TNF-α) in cells were detected via Polymerase Chain Reaction (PCR) and Western blotting. RESULTS: The serum PCS concentration in high-fat ApoE-/- mice was increased, and the aortic arch sections of ApoE-/- mice treated with PCS displayed the evident atherosclerotic plaques. Experimental results of human umbilical vein endothelial cells showed that the activity of human umbilical vein endothelial cells treated with PCS declined, the expression levels of TLR4, TREM-1, and TNF-α were increased, while that of p-eNOS was decreased. After the TLR4 knockout, the above effects of PCS were reversed. CONCLUSIONS: PCS damages vascular endothelial cells through TRL4/TREM-1, thereby accelerating the formation of atherosclerosis.

Circular RNA circ-NT5C2 acts as a potential novel biomarker for prognosis of osteosarcoma.

OBJECTIVE: Recent evidence suggests that circular RNAs (circRNAs) play important roles in multiple diseases, including cancer. Circ-NT5C2 was reported to be up-regulated in osteosarcoma. However, the clinical significance of circ-NT5C2 remains largely unclear. The aim of the current study was to investigate the value of circ-NT5C2 for the prognosis of patients with osteosarcoma. PATIENTS AND METHODS: the expression of circ-NT5C2 in osteosarcoma tissues and corresponding normal tissues were explored by quantitative real-time polymerase chain reaction (qRT-PCR) experiments. The association of circ-NT5C2 expression with clinicopathological factors or the prognosis of osteosarcoma patients was also analyzed. Kaplan-Meier survival analysis was performed to analyze the association of circ-NT5C2 expression with overall survival (OS) and disease-free survival (DFS) of patients. Univariate and multivariate Cox-regression analyses were used to identify risk factors for poor prognosis. RESULTS: Our data showed a significant increase of circ-NT5C2 expression in osteosarcoma tissues compared with adjacent normal bone tissues (p < 0.01). In addition, we found that the level of circ-NT5C2 in osteosarcoma was strongly correlated with clinical stage (p = 0.006) and distant metastasis (p = 0.001). Importantly, patients with high expression of circ-NT5C2 had a shorter OS (p = 0.006) and DFS (p = 0.001) than those with low expression of circ-NT5C2. Finally, Cox regression analyses showed that high circ-NT5C2 expression might be an independent prognostic parameter to predict poor prognosis. CONCLUSIONS: Our findings indicated that circ-NT5C2 is significantly up-regulated in osteosarcoma tissues. Circ-NT5C2 may represent a new marker of prognosis in osteosarcoma.

lncRNA HOXA11-AS is involved in fracture healing through regulating mir-124-3p.

OBJECTIVE: Long noncoding RNAs (lncRNAs) have been reported to participate in many diseases. Fracture healing is one of these ordinary diseases. This study aims to identify how lncRNA HOXA11-AS affects the progression of fracture healing. MATERIALS AND METHODS: RT-qPCR was performed to detect the level of HOXA11-AS. Moreover, function assays including cell growth assay and cell apoptosis assay were performed to explore how HOXA11-AS functions in fracture healing. Furthermore, the interaction between HOXA11-AS and mir-124-3p was studied by RT-qPCR, luciferase assay, and RNA immunoprecipitation assay. Rescue experiments were performed to verify the interaction between HOXA11-AS and mir-124-3p in vitro. RESULTS: In the research, function assays revealed that HOXA11-AS overexpression inhibited cell proliferation, while HOXA11-AS knockdown promoted cell proliferation in vitro. Moreover, HOXA11-AS overexpression promoted cell apoptosis, while HOXA11-AS knockdown inhibited cell apoptosis in vitro. Furthermore, mechanism assays demonstrated that HOXA11-AS acts a ceRNA via sponging mir-124-3p. Rescue assay demonstrated that HOXA11-AS suppressed cell proliferation and promoted cell apoptosis via targeting mir-124-3p. CONCLUSIONS: These results indicate that HOXA11-AS could inhibit cell proliferation and promote cell apoptosis of osteoblast via sponging mir-124-3p, which may offer a new vision for interpreting the mechanism of fracture healing.

The adverse effects of long-term l-carnitine supplementation on liver and kidney function in rats.

Levo-Carnitine (l-carnitine) is widely used in health and food. This study was to focus on the adverse effects of 8-week oral supplementation of l-carnitine (0.3 and 0.6 g/kg) in female and male Sprague Dawley rats. l-carnitine reduced body and fat weights, as well as serum, liver, and kidney lipid levels in rats. Simultaneously, hepatic fatty acid ß-oxidation and lipid synthesis were disturbed in l-carnitine-fed rats. Moreover, l-carnitine accelerated reactive oxygen species production in serum and liver, thereby triggering hepatic NOD-like receptor 3 (NLRP3) inflammasome activation to elevate serum interleukin (IL)-1ß and IL-18 levels in rats. Alteration of serum alkaline phosphatase levels further confirmed liver dysfunction in l-carnitine-fed rats. Additionally, l-carnitine may potentially disturb kidney function by altering renal protein levels of rat organic ion transporters. These observations may provide the caution information for the safety of long-term l-carnitine supplementation.

APP expression, distribution and accumulation are altered by aluminum in a rodent model for Alzheimer's disease.

Up-regulated expression of amyloid precursor protein (APP) occurs early in the cascade of events that leads to amyloid plaque formation in the human brain. APP gene up-regulation, mediated by activated NF-kappaB, is a response to stress from nM concentrations of aluminum ions, aluminum-disregulated iron ions, reactive-oxygen species, cytokines, and physical trauma. We examined in vivo effects of aluminum on APP in aged rats, obtained from previously-reported longitudinal studies, that chronically ingested aluminum in amounts equivalent to total dietary aluminum levels that Americans routinely ingest. These rats exhibited two outcomes: one group remained cognitively-intact, scoring as well on a memory-discrimination task in old age as in middle age. The other developed cognitive deterioration, obtaining significantly lower mean performance scores in old age than in middle age and exhibiting abnormal behaviors associated with dementia. We compared the expression, distribution and accumulation of APP in hippocampal and cortical tissue of these two rat groups. Compared to results from cognitively-intact rats, hippocampal and cortical tissue from the cognitively-deteriorated rats showed elevated APP gene expression, significantly more dense APP deposits in cytoplasm of neural cells, and APP-immunoreactive neurites that were swollen and varicose. This study shows aluminum routinely derived from chronic oral ingestion, that gradually accumulates in brain regions important for memory-processing, is sufficient to increase APP levels in neural cells of those regions. Aluminum may thus launch the cascade that results in the formation of amyloid plaques in human brain.

Addition of nitric oxide via nitroflurbiprofen enhances the material properties of early healing of young rat Achilles tendons.

OBJECTIVE AND DESIGN: To determine if the addition of nitric oxide (NO) via nitroflurbiprofen (NO-flurbiprofen) would enhance rat Achilles tendon healing. MATERIALS AND METHODS: Sixty-five male Sprague-Dawley rats were randomly divided into NO-flurbiprofen, flurbiprofen and vehicle groups, given drugs or vehicle subcutaneously, and their right Achilles tendon divided. Histological assessment was carried out at day 5, 10, and 15 post-operation. Healing tendon biomechanical properties and hydroxyproline content were measured at day 10. RESULTS: The healing Achilles tendon from the NO-flurbiprofen and flurbiprofen groups showed a better organization of extracellular collagenous matrix than that from the vehicle group. Flurbiprofen and NO-flurbiprofen decreased healing tendon cross-sectional area by 30% and 20%. This reduction was accompanied by a decreased failure load in the flurbiprofen group, but not the NO-flurbiprofen group. NO-flubiprofen prevented the reduction of body weight gain observed in the flubiprofen group. CONCLUSION: Both flurbiprofen and NO-flurbiprofen promoted better collagen reorganization during tendon healing. NO-flurbiprofen further improved tendon healing by increasing tendon stress and reducing the side effects (body weight loss) of flurbiprofen. The enhanced tendon healing by NO-flurbiprofen is likely due to the release of NO from the compound.