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Background: Revision of any neck surgeries is usually associated with increased rate of complications compared to the initial surgery due to adhesions. Especially, recurrent laryngeal nerve injury and hypoparathyroidism are most important postoperative complications of thyroid revision surgery. This study aimed to reveal anti-adhesive effects of cross-linked hyaluronic acid gel (NCHAG) in thyroid surgery. Materials and methods: This study was performed in 16 adult male rats who underwent hemithyroidectomy in the right lobe and randomized into two experimental groups: Group I (control group) was given any substance and Group II (NCHA group) received NCHA spray into their perithyroidal area. The rats were sacrificed after three weeks of thyroidectomy for assessment. Results: Gross adhesions score (x = 2.500) was significantly higher in Group I than Group II (x=1.750; P = 0.031). Group II showed significantly less fibrosis compared to the Group I (P = 0.002). The rate of inflammation was found to be significantly higher in group I (P = 0.008). Vascular proliferation was not different between two groups (p=0.083). Conclusions: Our study showed that NCHA can reduce postoperative adhesion and might be effective in preventing fibrosis after the thyroidectomy. Although this study could not demonstrate that application of NCHA is able to reduce complication rate in revision neck surgery, it could be safely used after thyroidectomy and neck surgeries to prevent adhesions.

Background Considerable disparities exist on the use of adipose tissue-derived stem cells (ADSCs) for treatment of spinal cord injury (SCI). Hence, the current systematic review aimed to investigate the efficacy of ADSCs in locomotion recovery following SCI in animal models. Methods A search was conducted in electronic databases of MEDLINE, Embase, Scopus, and Web of Science until the end of July 2019. Reference and citation tracking and searching Google and Google Scholar search engines were performed to achieve more studies. Animal studies conducted on rats having SCI which were treated with ADSCs were included in the study. Exclusion criteria were lacking a non-treated control group, not evaluating locomotion, non-rat studies, not reporting the number of transplanted cells, not reporting isolation and preparation methods of stem cells, review articles, combination therapy, use of genetically modified ADSCs, use of induced pluripotent ADSCs, and human trials. Risk of bias was assessed using Hasannejad et al.’s proposed method for quality control of SCI-animal studies. Data were analyzed in STATA 14.0 software, and based on a random effect model, pooled standardized mean difference with a 95% confidence interval was presented. Results Of 588 non-duplicated papers, data from 18 articles were included. Overall risk of bias was high risk in 8 studies, some concern in 9 studies and low risk in 1 study. Current evidence demonstrated that ADSCs transplantation could improve locomotion following SCI (standardized mean difference = 1.71; 95%CI 1.29–2.13; p I2 = 72.0%; p pfor odds ratios > 0.05). Conclusion We conclude that any number of ADSCs by any prescription routes can improve locomotion recovery in an SCI animal model, at any phase of SCI, with any severity. Given the remarkable bias about blinding, clinical translation of the present results is tough, because in addition to the complexity of the nervous system and the involvement of far more complex motor circuits in the human, blinding compliance and motor outcome assessment tests in animal studies and clinical trials are significantly different.

Aims The aims of this study were to develop an in vivo model of periprosthetic joint infection (PJI) in cemented hip hemiarthroplasty, and to monitor infection and biofilm formation in real-time. Methods Sprague-Dawley rats underwent cemented hip hemiarthroplasty via the posterior approach with pre- and postoperative gait assessments. Infection with Staphylococcus aureus Xen36 was monitored with in vivo photoluminescent imaging in real-time. Pre- and postoperative gait analyses were performed and compared. Postmortem micro (m) CT was used to assess implant integration; field emission scanning electron microscopy (FE-SEM) was used to assess biofilm formation on prosthetic surfaces. Results All animals tolerated surgery well, with preservation of gait mechanics and weightbearing in control individuals. Postoperative in vivo imaging demonstrated predictable evolution of infection with logarithmic signal decay coinciding with abscess formation. Postmortem mCT qualitative volumetric analysis showed high contact area and both cement-bone and cement-implant interdigitation. FE-SEM revealed biofilm formation on the prosthetic head. Conclusion This study demonstrates the utility of a new, high-fidelity model of in vivo PJI using cemented hip hemiarthroplasty in rats. Inoculation with bioluminescent bacteria allows for non-invasive, real-time monitoring of infection. Cite this article: Bone Joint J 2021;103-B(7 Supple B):9–16.

Background and aim An injection solution is required to create a submucosal cushion (SMC) for safe endoscopic resection procedures. The aim of this preliminary animal study was to clarify the safety and efficacy of a novel fully synthetic and self-assembled peptide (FSSP) solution as a submucosal injection material (SMIM). Method To compare the submucosal-lifting properties, 0.3% FSSP, Eleview®, sodium hyaluronate acid solution (SHA) and normal saline (NS) were randomly injected using an injection needle into the submucosa of exposed stomach and colon in five living dogs in a blind fashion. The mean height, and volume of SMCs were measured using a digital caliper immediately and 10, 20, 30, and 40 min after injecting each solution. All resected specimens were examined histopathologically. Results In both the colon and stomach, ANOVA for repeated measures showed the significant interaction between time and solution for the time-dependent change in the height. In the colon, FSSP created significantly higher SMC than NS 20 min after injection (p = .0015) and Eleview® and NS 40 min after injection (p = .0009 and p = .0002). Furthermore, FSSP and SHA tended to maintain height and volume when compared to the other two solutions. In the stomach, FSSP and SHA tended to maintain height and volume when compared to the other two solutions. There were no significant differences between the histopathological finding and the injecting solutions used. Conclusion FSSP seems to be useful as a SMIM for endoscopic resection especially in the colon. Further studies are needed prior to clinical use of FSSP.

Background/aims Irreversible electroporation (IRE) is a relatively new ablation method. However, the application of IRE ablation in the treatment of biliary disease has not been attempted. A minimally invasive approach using endoscopic retrograde cholangiopancreatography (ERCP) can be a novel therapeutic modality for IRE ablation. In this study, we aimed to investigate the feasibility of endoscopic IRE for the biliary tract using an animal model. Methods A new catheter-type electrode was developed for endoscopic IRE ablation of the biliary tract. We performed ERCP and endoscopic IRE ablations in the normal common bile duct of Yorkshire pigs. The experimental setting of IRE was 500 V/cm (50 pulses, 100-µs length). The animals were sacrificed after 24 hr, and the ablated bile duct was examined. Results Well-demarcated focal color changes were observed on the mucosa of the common bile duct. The depth of change after IRE was confined to the mucosal and submucosal layers. Apoptotic changes in the bile duct were observed only around the IRE ablation area. Immunohistochemistry assay showed cell death in the bile duct along the electrode. Conclusions Endoscopic IRE ablation using ERCP was successfully performed in the common bile duct. It can be a potential option for the treatment of biliary tumors.

Background/Aim: Bisphosphonate-related osteonecrosis of the jaw (BRONJ) was first introduced in 2003 and its scope was expanded by the name medication-related osteonecrosis of the jaw (MRONJ), since 2014. This study aimed to evaluate the effects of photodynamic therapy (FDT) on tissue samples by histopathological and histomorphometric examination and serum TRACP-5b (Tartrateresistant acid phosphatase-5b) measurement in rats. Material and Methods: 24 Sprague-Dawley male rats were divided into 3 groups comprising 8 animals. Zoledronic acid was administered to groups 1 and 2 and 0.9% sodium chloride was administered to group 3 intraperitoneally. After the injections were completed, dental extractions were performed. Photodynamic therapy was applied to group 2, three times a week for the two weeks after the extraction. In the 16th week, sacrification was performed. Rats were undergone histopathologic and histomorphometric evaluations. Results: Photodynamic therapy has led to a decrease in epithelial opening and inflammation and an increase in the formation of new bone. Serum TRACP-5b values were shown to decrease significantly in the presence of osteonecrosis. Conclusions: PDT was shown to be useful in reducing MRONJ risk in rats. As a serum biomarker, Serum TRACP-5b could be a valuable marker. Additional studies should confirm the findings.

Made available in DSpace on 2021-06-25T10:22:10Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-01-01 Aim: To evaluate the modifications and possible perforations of the sinus mucosa lining graft particles and implant surfaces after sinus lifting. Material and methods: Twelve New Zealand rabbits underwent a bilateral sinus lifting using either autogenous bone harvested from the tibia (AB; autogenous bone group) or deproteinized bovine bone mineral (DBBM group) as filler. Implants were simultaneously installed. Thinned sites (

The aim of this paper is to introduce basic concepts and methods for calculating sample size in animal studies. At the planning stage of clinical studies, the determination of the sample size is a very important process to show the validity, accuracy, and reliability of the study. However, not all studies require a sample size to be calculated. Before conducting the study, it is essential to determine whether the study objectives suggest a pilot and exploratory study, as well as the purpose of testing the hypothesis of interest. Since most animal experiments are pilot and exploratory studies, it would be more appropriate to review other considerations for conducting an experiment while maintaining scientific and qualitative levels rather than sample size estimation. Sample size is calculated in various situations in animal studies. Therefore, it can be estimated according to the situations and objectives through the methods of precision analysis, power analysis, and so on. In some cases, nonparametric methods can be employed if the assumptions of normality is not met or a small sample is available for the study.

Simvastatin (SMV) could increase tooth anchorage during orthodontic tooth movement (OTM). However, previous studies on its bone‐specific anabolic and anti‐inflammation properties were based on static in vitro and in vivo conditions. AMPK is a stress‐activated kinase that protects tissue against serious damage from overloading inflammation. Rat periodontal ligament cells (PDLCs) were subjected to a serial of SMV concentrations to investigate the optimization that promoted osteogenic differentiation. The PDLCs in static and/or tensile culturing conditions then received the proper concentration SMV. Related factors expression was measured by the protein array, real‐time PCR and Western blot. The 0.05UM SMV triggered osteogenic differentiation of PDLCs. The inhibition of AMPK activation through a pharmacological approach (Compound C) caused dramatic decrease in osteogenic/angiogenic gene expression and significant increase in inflammatory NF‐κB phosphorylation. In contrast, pharmacological activation of AMPK by AICAR significantly inhibited inflammatory factors expression and activated ERK1/2, P38 MAPK phosphorylation. Moreover, AMPK activation induced by SMV delivery significantly attenuated the osteoclastogenesis and decreased the expression of pro‐inflammatory TNF‐α and NF‐κB in a rodent model of OTM. The current studies suggested that SMV could intrigue intrinsic activation of AMPK in PDLCs that promote attenuate the inflammation which occurred under tensile irritation through AMPK/MAPK/NF‐kB Inhibition.

The response of the dentin-pulp complex in rat teeth was investigated after direct capping with biodentine with or without bone marrow-derived stem cells (BMDSCs). Following mechanical exposure, pulps were randomly capped with one of the followings materials: calcium hydroxide, biodentine or 1 × 105 BMDSCs mL-1 + biodentine. Histological examination was performed by light microscopy after 1, 3 and 5 weeks. Inflammatory reaction, necrotic tissue formation and calcific bridge formation were scored. Analysis showed that compared with the effects of calcium hydroxide or biodentine, BMDSCs + biodentine substantially reduced inflammatory reaction and necrotic tissue while promoting calcified tissue formation. Therefore, the combination of biodentine and BMDSCs could potentially stimulate pulp tissue regeneration after direct pulp capping.

Highlights •MR continues to be a challenge encountered in clinical practice. If left untreated, the effects are far reaching with LV volume overload, pulmonary hypertension, and potentially progression into severe heart failure. Many patients are not routinely offered surgery because of comorbidities and perceived surgical risk. •The Mitral Butterfly is a novel device offering minimally invasive repair of a prolapsing valve with a simple, single-step deployment. This catheter-based device is composed of a nitinol frame and a polymer matrix covering the entire prolapsing segment of the insufficient valve. Unlike other chordal repair techniques, there is no need for myocardial fixation. •Device performance in a 90-day chronic animal study and in silico analysis substantiated the underlying device concept. •Progress continues to be made in developing a safe and effective transcatheter alternative for MV repair.

Background: This work aimed to evaluate the influence of two chelators: DOTA(SCN) and DOTA(NHS) on radioimmunotherapy using 177Lu-DOTA-Rituximab preparations in murine lymphoma xenograft models. Su...

Kuzucu, İhsan ( Aksaray, Yazar ), OBJECTIVES: The aim of this study was to assess whether nivolumab is ototoxic in rats and whether this ototoxicity is dose-dependent. MATERIALS AND METHODS: Twelve rats were divided into two groups: Group 1 (control group, 6 rats, 12 ears) received intraperitoneal saline for 14 days. Group 2 (study group, 6 rats, 12 ears) and received two doses of 3 mg/kg intraperitoneal nivolumab within 14 days. Auditory brainstem responses (ABRs) were performed preoperatively and 4 and 8 weeks postoperatively. We compared between the groups, morphologic appearance of spiral ganglion cells and organ of Corti and density of spiral ganglion cells (measured with conventional light microscope connected to a personal computer). RESULTS: In our control group, both spiral ganglion and organ of corti had a normal morphological appearance. In our study group, spiral ganglion cells had a normal morphological appearance. However, some sections showed possibly mild degenerative changes in the organ of corti. Of 12 samples in the study group, four had a significant loss of density of spiral ganglion cells compared to the control group. The baseline ABR thresholds did not significantly differ between the groups (p=0.713). There was no statistically significant difference between the groups regarding ABR thresholds at week 4 (p=0.347). However, a statistically significant difference was observed in the ABR thresholds at week 8 (p=0.045). CONCLUSION: The results of our study showed that nivolumab treatment has ototoxic effects. Based on our results, we recommend monitoring the changes in the hearing ability of chemotherapy patients.

Background: In recent years, the use of the anterior half of the peroneus longus tendon (AHPLT) as an autograft source for ligament reconstruction has gained popularity. However, no reports are available regarding tendon regeneration after harvesting of the AHPLT. Hypothesis: When half of the tendon is preserved during tendon harvesting, the quality of the regenerated tendon is better than that of the regenerated tendon after full-thickness harvesting. Study Design: Case series; Level of evidence, 4; controlled laboratory study. Methods: A total of 21 patients who underwent AHPLT harvesting for lower extremity ligament reconstruction participated in the magnetic resonance imaging (MRI) study to evaluate tendon regeneration 1 year after the harvesting. An in vivo animal study was performed to compare the quality of the regenerated tendon after partial-thickness and full-thickness tendon harvesting. A total of 30 adult female Sprague-Dawley rats were allocated to 2 groups—15 rats underwent partial-thickness Achilles tendon harvesting (partial-thickness harvesting [PTH] group), and 15 rats underwent full-thickness Achilles tendon harvesting (full-thickness harvesting [FTH] group). The quality of the regenerated tendons was compared 180 days after tendon harvesting. Results: All 21 patients showed regeneration of the peroneus longus tendon (PLT) (homogeneously dark on both T1- and T2-weighted sequences). The cross-sectional area of the regenerated tendon divided by that of the preoperative tendon was 92.6% and 84.5% at 4 cm and 9 cm proximal to the tip of the distal fibula, respectively. In the animal study, the mean histologic score was better for the PTH group compared with the FTH group (9.17 ± 1.35 vs 14.72 ± 0.74; P < .001). The ultimate strength and the stiffness of the regenerated Achilles tendon were significantly higher for the PTH group compared with the FTH group (35.5 ± 8.3 vs 22.4 ± 8.3 N, P = .004; and 31.6 ± 7.7 vs 23.5 ± 4.8 N/mm, P = .016). Conclusion: The PLT was found to regenerate after partial-thickness harvesting on MRI. In the animal study, the quality of the regenerated tendon when half of the tendon was preserved during tendon harvesting was better than that after full-thickness tendon harvesting.

Objectives Dual-energy and multienergy computed tomography (DECT/MECT) has the potential to simultaneously visualize two contrast agents in the small bowel: arterial enhancement of iodine in the bowel wall and enteric enhancement of bismuth in the bowel lumen. The purpose of this study was to explore its feasibility in a swine study using a research whole-body photon-counting-detector (PCD) computed tomography (CT) system. Materials and methods A phantom study was initially performed to evaluate the quantification accuracy of iodine and bismuth separation from a single PCD-CT scan, which also served as the calibration reference for material decomposition of in vivo swine PCD-CT data. In the animal study, a test bolus scan was first performed to determine the time-attenuation curve for the arterial enhancement, based on which the timing of the PCD-CT dual-contrast scan was determined. A 600 mL homogeneous bismuth-saline solution (180 mL Pepto-Bismol + 420 mL normal saline) was orally administered to the pig using esophageal intubation. Approximately 1 hour after bismuth administration, 40 mL iodine contrast (Omnipaque 350, 5 mL/s) was injected intravenously. A PCD-CT scan was performed 13 seconds after the initiation of the contrast injection to simultaneously capture the arterial enhancement of iodine and the enteric enhancement of bismuth. To provide optimal material separation and quantification, all PCD-CT scans in both phantom and animal studies were operated at 140 kV with 4 energy thresholds of 25, 50, 75, and 90 keV. Results Using a generic image-based material decomposition method, the iodine and bismuth samples were successfully delineated and quantified in the phantom images with a root-mean-square-error of 1.32 mg/mL in iodine measurement and 0.64 mg/mL in bismuth measurement. In the pig study, the enhancing bowel wall containing iodine and the small bowel loop containing bismuth were not differentiable in the original PCD-CT images. However, they were clearly distinctive from each other in the iodine- and bismuth-specific images after material decomposition, as reviewed by an abdominal radiologist. In addition, quantitative analysis showed that the misclassification between the two contrast materials was less than 1.0 mg/mL. Conclusions Our study demonstrated the feasibility of simultaneous imaging of iodine and bismuth in small bowel of swine using PCD-CT.

One of the challenges of ocular drug delivery systems is sustainable delivery of the intended drug to the posterior segment of the eye. Periocular routes of drug delivery are a promising method to bridge this challenge. The purpose of this study is to investigate the recent advances and potentials of subconjunctival route and its pros and cons in comparison with other ocular drug delivery routes. In this literature review, the comprehensive search of publications was performed in MEDLINE/PubMed indicating investigations on subconjunctival drug delivery systems using relevant keywords. Based on the resultant detailed criteria to choose an appropriate ocular drug delivery route, it is revealed that most of these routes are either highly invasive and/or provide low bioavailability of drug to the target tissue. Nevertheless, subconjunctival drug delivery could be considered as one of the less invasive and easily accessible routes for delivering various drugs to both anterior and posterior segments of the eye. However, most of such researches are at the stage of animal study in their pipelines. Periocular route of drug delivery is one of the most efficient routes for delivering the drugs to both anterior and posterior segments of the eye. Subconjunctival sustained drug delivery is highly effective and less invasive compared to other periocular routes. This makes subconjunctival implants and injections one of the most proper ways of treating various ranges of ocular diseases and disorders, e.g., diabetic retinopathy, dry eye syndrome, glaucoma, etc.

Small molecules including sodium butyrate (SB) and dimethyloxalylglycine (DMOG) can promote bone regeneration via inhibitive effects eliciting cellular responses through signaling cascades. The purpose of this study was to determine the synergistic effects of SB and DMOG loaded on calcium sulfate (CaS) on bone regeneration in the challenging vertical augmentation model in the rabbit calvarium. Four plastic cylinders screwed on the calvarium of each of 10 rabbits were randomly grafted with CaS, CaS/SB, CaS/DMOG, or CaS/DMOG/SB. All specimens were assessed by radiographic, histologic, and histomorphometric analyses. In the radiographic analysis, three different layers (new bone, degraded CaS, and pristine CaS layers) could be distinguished within the cylinder in all groups at 2 weeks. Newly formed bone grew up from basal bone, and CaS in contact with newly formed bone was degraded into small particles to form a different layer. At 8 weeks, most of the pristine CaS had been absorbed and hardly seen within the cylinder. In the histomorphometric analysis, all groups showed comparable new bone areas and heights at 2 and 8 weeks. The DMOG group showed a significant increase in new bone area at 8 weeks compared with 2 weeks, but there was no significant difference among the groups at 8 weeks. The DMOG group showed significantly lower values for the residual material area than the control group at 2 weeks. Within the limitations of this study, SB and DMOG seem to exert smaller synergistic effects on bone regeneration compared to CaS alone in vertical bone augmentation.

Background: To verify the hypothesis that the nature of trigeminal neuralgia (TN) is an ectopic impulse induced by sodium channel modulated by cytokines, we conducted an animal study using the infr...

Aim: To compare strontium ranelate as a pulp capping agent to bisphosphonate and calcium hydroxide. Materials and methods: The pulps of 36 premolars from 4 dogs were exposed and capped with one of 3 test materials, namely strontium ranelate, bisphosphonate, and calcium hydroxide. Half of the specimens underwent histologic evaluation at 6 weeks and the remaining half were assessed at 12 weeks. Each slide was scored from 1 to 3 according to hard tissue formation, inflammation, and odontoblastic differentiation. The pH of the 3 materials was also measured. Data were inspected using SPSS software and the recorded scores were statistically analyzed at 6 and 12 weeks. Results:Calcium hydroxide was the only material that exhibited discontinuous dentin bridge at both evaluation periods. Strontium ranelate showed irregular hard tissue formation in few of the samples at 12 weeks; while bishphonate did not induce any hard tissue formation. All the materials exhibited severe to moderate inflammatory reaction at 6 weeks which subsided to mild inflammation at 12 weeks. Differentiation of odontoblasts was observed with all materials at both evaluation periods with no significant differences among them. The average pH obtained for Dycal base was 9, and 12 for the catalyst; for bisphosphonate the value was 6.8; and 8.6 for strontium ranelate. Conclusions: Strontium ranelate was not as effective as calcium hydroxide as a pulp capping agent, while bisphosphonate failed to show any potential for hard tissue formation up to 12 weeks. However, all the test materials allowed healing of the pulp tissues.

Purpose Treatment of wide-necked intracranial aneurysms using the Woven Endobridge (WEB) device has become broadly accepted. Feared complications with the potential of increased poor clinical outcome include dislocations and migration of the device. This study was carried out to determine the effectiveness of a variety of different strategies to rescue migrated WEB devices. Methods In a porcine model, WEB devices of different sizes (SL [single layer] 3.5 × 2mm and SL 4.0 × 3 mm, SL 8 × 5 mm and SLS 8 mm [single layer spherical]) were placed into both the subclavian and axillary arteries. A total of 32 rescue maneuvers (8 per rescue device) were performed. Small WEBs were rescued using reperfusion catheters (RC) (SOFIA Plus and JET 7), larger WEBs were rescued using dedicated rescue devices (Microsnare and Alligator). Rescue rates, times, attempts and complications were assessed. Results Rescue attempts of migrated WEBs were successful in all cases (100%). Rescue time (p = 0.421) and attempts (p = 0.619) of small WEBs using RCs were comparable without significant differences. Aspiration alone was not successful for larger WEBs. Rescue of larger WEBs was slightly faster (122.75 ± 41.15 s vs. 137.50 ± 54.46 s) with fewer attempts (1 vs. 1.37) when using the Microsnare compared to the Alligator device. Complications such as entrapment of the WEB in the RCs, vasospasm, perforation, or dissection were not observed. Conclusion Rescue of migrated WEB devices is a feasible and effective method and 100% successful rescue rates and appropriate rescue times can be achieved for small WEBs using RCs and for larger WEBs using dedicated rescue devices (Microsnare and Alligator).

The aim of this study was to investigate the outcomes of direct pulp capping performed with two types of tricalcium silicate-based materials (mineral trioxide aggregate/MTA and Biodentine/BD); nano-hydroxyapatite (nHAP) crystals or calcium hydroxide (CH) in dogs. Following mechanical exposure, the pulps were randomly capped with one of the four materials. Histological analyses were performed to examine the outcomes after 7 days or 3 months. At 7 days, BD and nHAP showed significantly less inflammatory cell response than MTA and CH. At 3 months, the inflammatory cell response and tissue necrosis were significantly higher in the CH group. There was no significant difference between the tested materials in the calcific bridge formation after 7 days; however, a significant difference was noticed at the 3-month period. Tricalcium silicate-based cements and nHAP are potential alternatives to CH in vital pulp therapy following accidental pulp exposure.

Introduction Despite technical progress, ventricular tachycardia (VT) recurrence after unipolar ablation remains relatively high (12%-47%). Bipolar ablation has been proposed as an appealing solution that may overcome limitations associated with unipolar ablation settings. We designed an animal study to compare bipolar (BPA) vs sequential unipolar ablation (UPA) using contact force-sensing technology on both ablation catheters. Methods Twenty large white female pigs (6-months-old, 50-60 kg) underwent multiple RF ablations (30 W, 60 seconds, 30 mL/min irrigation) on the ventricular myocardium from the epicardial and endocardial sides. The hearts were fixed and scanned with high-resolution cardiac magnetic resonance imaging. Thermal lesions were located and characterized in volume, depth, width, and transmurality. Results Lesion volume was calculated as the sum of epicardial or endocardial conjoined/isolated lesions at one location. Linear dimensions (width and depth) were measured twice for each location, on the endocardial and epicardial side. We evaluated 35 lesions across the intraventricular septum (UPA, N = 17 vs BPA, N = 18). No difference in volume, linear dimensions or impedance drop was observed in this area between UPA and BPA. However, BPA required half RF time and showed an increased transmurality trend. We then analyzed 73 lesions from the endocardial side (UPA, N = 35 vs BPA, N = 38) and 50 from the epicardial side (UPA, N = 11 vs BPA N = 39) of the ventricular free walls. Lesion transmurality was markedly improved by BPA (P = .030, odds ratio, 23.73 [4.71,31.96]). Ventricular BPA lesions were significantly deeper on the epicardial side (P < .0001) and endocardial side (P = .015). Conclusion Bipolar ablation is more likely to create transmural and epicardial lesions in the ventricle wall. Half the time is needed for the creation of comparably deep and large lesions.

Micropigmentation, also termed medical tattooing, can be a useful alternative treatment for patients with vitiligo who are resistant to conventional treatments. To assess the benefits and risks of micropigmentation in the treatment of refractory vitiligo, 25 lesions of 14 patients with vitiligo (Fitzpatrick skin types III and IV) were subjected to micropigmentation using an electric tattooing machine between December 2018 and March 2019. The procedure was repeated until satisfactory results were obtained. Treatment response was assessed by color matching of the treated lesion and surrounding skin using a 4-point scale (poor, fair, good and excellent). Excellent color matching was achieved in 80% (20/25) of cases after a median of three (range, 1-5) treatment sessions. Procedure-associated pain was considerable, but no anesthetic injection was needed. Immediate erythema and swelling were noticed after each procedure, but resolved within a few days. Overall, the treatment was tolerable. This study was limited by a small sample, no control group and a short follow-up period. This study revealed that micropigmentation was beneficial for patients with refractory vitiligo who had light to moderately colored skin. Pigment selection, implantation depth and selection of body parts amenable to treatment were critical.

Several different biomaterials are being introduced for clinical applications. However, no current material-specific systematic studies define parameters for evaluating these materials. The aim of this retrospective animal study is to classify biomaterials according to the in vivo induced cellular reaction and outline the clinical consequence of the biomaterial-specific cellular reaction for the regeneration process. A retrospective histologic analysis was performed for 13 polymeric biomaterials and 19 bone substitute materials (BSMs) (of various compositions and origins) that were previously implanted in a standardized subcutaneous model. Semiquantitative analyses were performed at days 3, 15, and 30 after implantation according to a standardized score for the induction of multinucleated giant cells (MNGCs) and vascularization rate. The induced cellular reaction in response to different polymeric materials allowed their classification according to the MNGC score in the following groups: class I induced no MNGCs at any time point, class II induced and maintained a constant number of MNGCs over 30 days, and class III induced MNGCs and provided an increasing number over 30 days. All BSMs induced MNGCs to varying extents. Therefore, the resultant BSM classifications are as follows: class I induced MNGCs with a decreasing number, class II induced and maintained constant MNGCs over 30 days, and class III induced MNGCs with increasing number over 30 days. These observations were mostly related to the biomaterial physicochemical properties and were independent of the biomaterial origin. Consequently, the induction of MNGCs and their increase over 30 days resulted in disintegration of the biomaterial. By contrast, the absence of MNGCs resulted in an integration of the biomaterial within the host tissue. This novel classification provides clinicians a tool to assess the capacity and suitability of biomaterials in the intended clinical indication for bone and soft tissue implantations.

Objectives Contrast-enhanced computed tomography (CECT) is used to monitor technical success immediately after hepatic microwave ablation (MWA). However, it remains unclear, if CECT shows the exact extend of the thermal destruction zone, or if tissue changes such as peri-lesionary edema are depicted as well. The objective of this study was to correlate immediate post-interventional CECT with histological and macroscopic findings in hepatic MWA in porcine liver in vivo. Methods Eleven MWA were performed in porcine liver in vivo with a microwave generator (928 MHz; energy input 24 kJ). CECT was performed post-interventionally. Livers were explanted and ablations were bisected immediately after ablation. Samples were histologically analyzed after vital staining (NADH-diaphorase). Ablation zones were histologically and macroscopically outlined. We correlated histologic findings, macroscopic images and CECT. Results Three ablation zones were identified in histological and macroscopic findings. Only one ablation zone could be depicted in CECT. Close conformity was observed between histological and macroscopic findings. The ablation zone depicted in CECT overestimated the histological avital central zone and inner red zone (p .05). Conclusions Immediate post-interventional CECT overestimated the clinically relevant zone of complete cell ablation after MWA in porcine liver in vivo. This entails the risk of incomplete tumor ablation and could lead to tumor recurrence.

Background: The aim of this study was to determine the effect of low-level light therapy (LLLT) on orthodontic tooth movement (OTM) rate, heat shock protein 70 (HSP-70) expression, and matrix metalloproteinase 8 (MMP-8) expression. Materials and Methods: In this experimental study twenty-four male guinea pigs were randomly divided into three groups (n = 8): control group (K) without orthodontic force and LLLT; treatment group 1 (T1) with orthodontic force, and treatment group 2 (T2) with orthodontic force and LLLT. The labial surfaces of both maxillary central incisors in treatments groups were installed with single-wing bracket before being inserted with close coil spring to give 10 g/cm2 orthodontic force. For the T2 group, 4 J/cm2 of LLLT was administered in the mesial-distal and labial-palatal regions for 3 min every day. On day 14, the gap between teeth was measured and immunohistochemistry staining was done to determine HSP-70 and MMP-8 expression. Data were analyzed using (IBM, New York, (ANOVA), followed by Turkey's HSD test to determine the differences between groups. Nonnormal distributed data would be analyzed using Kruskal–Wallis test, followed by Mann–Whitney test with P < 0.05 being performed. Results: The gap between teeth in the T2 group was greater compared to T1 group (P = 0.00). However, there was a significant decrease of HSP-70 and MMP-8 expression in T2 group compared to T1 group in the tensile and compressive sides. Conclusion: LLLT intervention during orthodontic treatment could accelerate OTM rate and decreased HSP-70 and MMP-8 expression both in tension and in compressive side. Thus, LLLT interventions can be used as adjuvant therapy to shorten orthodontic treatment duration.

BACKGROUND Barbaloin is one of the main medicinal ingredients of aloe vera, which displays various anti-inflammatory and anti-apoptosis properties in several inflammatory and fibrotic diseases. Our study evaluated its efficacy against dextran sulfate sodium (DSS)-induced colitis in rats. MATERIAL AND METHODS Ulcerative colitis (UC) rat models were established in vivo, and after barbaloin treatment, body weight and inflammation index were measured. Additionally, the signaling mechanism by which barbaloin protects against UC was investigated using LPS-infected Caco-2 cells. RESULTS Barbaloin could significantly reverse UC-induced weight loss and colon injury. Further, it could effectively increase the mRNA expression of IL-4 and IL-10 in colon tissues, while decreasing the expression of IFN-γ, IL-6, IL-1ß, and TNF-alpha. Furthermore, it significantly enhanced UC-inhibited atresia band 1 (ZO-1), occludin, and E-cadherin, and was also found to activate the AMPK signaling pathway. Additionally, si-RAN-induced knockdown, and overexpression assay showed that barbaloin could inhibit the UC-enhanced MLCK signaling pathway by activating the AMPK signaling pathway. CONCLUSIONS Barbaloin can effectively inhibit inflammation and reverse epithelial barrier function to protect against UC, possibly via activation of the AMPK signaling pathway.

BACKGROUND Toothache often occurs with pulpitis. Lipopolysaccharide (LPS) is produced by gram-negative bacteria, and its accumulation is related to clinical symptoms of pain. MicroRNAs (miRNAs) display anti-inflammatory potential due to their direct regulation of cellular protein expression, which can promote inflammatory changes in dental pulp tissues. However, the mechanism of LPS-induced pulpitis is still unclear. MATERIAL AND METHODS In this study, dental pulp stem cells (DPSCs) were separated and cultured from rat dental pulp tissues; then, LPS was administered to induce inflammation and activate the TLR4 pathway. RESULTS It was found that miR-506 was upregulated following LPS treatment in DPSCs. The inhibition of miR-506 in LPS-treated DPSCs led to attenuated inflammation and deactivation of the TLR4 pathway. Furthermore, the bioinformatic analysis and dual-luciferase reporter gene assay indicated that miR-506 could target the 3'-UTR of sirtuin 1 (SIRT1). Additionally, SIRT1 decreased in LPS-treated DPSCs, and miR-506 transfection resulted in SIRT1 upregulation. SIRT1 overexpression showed a similar inhibitory effect as that of miR-506 downregulation on inflammation and TLR4 activation in DPSCs. CONCLUSIONS In brief, miR-506 can protect dental pulp in LPS-induced inflammation by inhibiting the SIRT1-mediated TLR4 pathway.

BACKGROUND The flavones are considered as competent antidiabetic molecules due to their strong antioxidant activities and higher in vivo stability. The present study evaluated the antidiabetic and hypolipidemic effects of 5,7-dimethoxyflavone in streptozotocin (STZ)-induced diabetic rat models. MATERIAL AND METHODS The antidiabetic potential of 5,7-dimethoxyflavone was evaluated in streptozotocin-induced diabetic rats. The serum levels of triglyceride, total cholesterol, and high-density lipoprotein cholesterol were measured using the Randox assay kit. Histopathological examination was carried out by hematoxylin and eosin (HE) staining. RESULTS Oral administration of 5,7-dimethoxyflavone significantly reduced STZ-induced enhancement in blood sugar and glycosylated hemoglobin, as well as significant increases in C-peptide, insulin, hemoglobin, and total protein content (p

BACKGROUND The phytochemical ingredients of berries have been used in the treatment of various bodily ailments; while their roles in preventing the severity of glaucoma are poorly understood. Hence, the present study was framed to investigate whether ethanolic extracts of Lycium barbarum exerts protection against the onset of glaucoma using cultured PC12 neuronal cells by modulating the expression of extracellular matrix proteins. MATERIAL AND METHODS In order to develop glaucoma like condition in cells, cultured PC12 cells were subjected to 50 and 100 mmHg hydrostatic pressure for 24 hours. The pressure exposed cells were analyzed for the expression of glaucoma markers such as ANGPTL7 and the expressions of extracellular matrix proteins in the presence and absence of L. barbarum, matrix metalloproteinase (MMP)-9 inhibitor, and latanoprost, a current drug for the treatment of glaucoma. RESULTS PC12 cells exposed to hydrostatic pressures (50 and 100 mmHg) increased the expression of glaucoma marker, ANGPTL7. Moreover, results have demonstrated the significant changes in the expression of MMP-2, MMP-9, collagen I, and TGF-ß at the gene level. In contrast, cells pretreated with L. barbarum extracts showed reduced expression of ANGPTL7 and extracellular matrix proteins compared to control. Furthermore, to elucidate the role of MMP-9 in the onset of glaucoma, cells were silenced using MMP-9 inhibitor along with L. barbarum demonstrated a significant reduction in the glaucoma marker ANGPTL7 while improving the expression of caveolin-1 expression in cells subjected to pressure. CONCLUSIONS The extract of L. barbarum protects the cells from intraocular pressure by activating caveolin-1 dependent pathway via inhibition of MMP-9 expression.

BACKGROUND The aim of this study was to determine the association between white matter lesions (WML) and diabetes-associated cognitive decline (DACD) in rat models of type 2 diabetes (T2DM). MATERIAL AND METHODS Sixty Sprague-Dawley male rats were divided into 4 groups: control, control+metformin, T2DM, and T2DM+metformin groups. The T2DM groups were fed a diet high in fat and glucose to induce impaired glucose tolerance (IGT) and then were injected with streptozotocin to induce T2DM. The Morris water maze test was used to evaluate cognitive function. Brain diffusion tensor imaging scans were performed for WML. The expression of myelin basic protein (MBP), oligodendrocyte transcription factor 1 (OLIG1), and OLIG2 (markers of brain damage and repair) was determined using immunofluorescence. After IGT, the fractional anisotropy (FA) values of the right thalamus area were significantly lower in both T2DM groups compared with controls. RESULTS Eight weeks after streptozotocin injection, the FA values of the thalamus were lower in the T2DM (bilateral thalamus) group and T2DM+metformin (left thalamus) group than in controls, while the FA values in the left thalamus area were lower in the T2DM+metformin group than in the control and control+metformin groups. The maze escape latency was longer and the number of rats passing through the platform was smaller in the T2DM and T2DM+metformin groups than in the control group. MBP levels were lower and OLIG1 and OLIG2 levels were higher in both T2DM groups than in controls. CONCLUSIONS WML is associated with DACD and appears before the onset of T2DM and signs of DACD and plays a role in diabetes-associated cognitive decline. Metformin reduces WMLs but does not rescue cognitive dysfunction.

BACKGROUND Cardiac myocyte hypertrophy results from clinical conditions that include hypertension and valvular heart disease, and can result in heart failure. This study aimed to investigate the expression and role of the long noncoding RNA FTX (lnc-FTX), an X-inactive-specific transcript (XIST) regulator transcribed from the X chromosome, in hypertrophy of neonatal mouse cardiac myocytes induced by angiotensin II (Ang II) in vitro. MATERIAL AND METHODS Cardiac myocytes were isolated from neonatal mice and cultured with and without Ang II. Immunofluorescence, with localization of an antibody to alpha-smooth muscle actin (alpha-SMA), was used to identify the neonatal mouse cardiac myocytes. Quantitative real-time polymerase chain reaction (qRT-PCR) measured gene expression levels. The cell counting kit-8 (CCK-8) assay was used to determine cell viability, and Western blot measured protein expression. StarBase v2.0 bioinformatics software was used for target gene prediction and was confirmed with the luciferase reporter assay. RESULTS The expression of lnc-FTX was reduced in mouse cardiac myocytes treated with Ang II. Overexpression of lnc-FTX reduced cell apoptosis, cardiomyocyte contractility, and the expression of c-Jun, A-type natriuretic peptide (ANP), and B-type natriuretic peptide (BNP) induced by Ang II. The target of lnc-FTX was micro-RNA 22 (miRNA-22). The mechanism of action of lnc-FTX in neonatal mouse cardiac myocytes was through suppression of the PI3K/Akt signaling pathway by promoting the release of PTEN by sponging miRNA-22. CONCLUSIONS The expression of lnc-FTX was associated with reduced hypertrophy of neonatal mouse cardiac myocytes and regulated the PTEN/PI3K/Akt signaling pathway by sponging miRNA-22.

BACKGROUND Intestinal dysbiosis, or dysbacteriosis, is an abnormal interaction between the intestinal microbiota and the host cells due to altered microbial diversity. This study aimed to investigate the metabolic effects and changes in the intestinal microbiota in newborn rats following exposure to increased levels of maternal androgens in a rat model of maternal polycystic ovary syndrome (PCOS). MATERIAL AND METHODS The administration of androgen developed the rat maternal PCOS model during pregnancy. Maternal rat ovarian follicles were counting and assessed by histology. The metabolic phenotype of newborn rats was evaluated and included an insulin tolerance test, a glucose tolerance test, and measurement of serum levels of triglyceride, insulin, cholesterol, adiponectin, and leptin. Expression of pro-inflammatory cytokines was detected using quantitative reverse transcription-polymerase chain reaction (qRT-PCR), serum levels were measured by enzyme-linked immunosorbent assay (ELISA), and proteins associated with adipose tissue remodeling and adipocyte differentiation were measured by Western blot. RESULTS Markers of systemic inflammation were significantly increased in the female offspring but not in the male offspring born to rat in the PCOS model. Following birth, newborn rats that received antibiotics showed an improved metabolic phenotype, with reduced serum lipid levels, insulin resistance, body weight, inflammation of adipose tissue, and serum levels of inflammatory cytokines compared with controls. Probiotics had no significant effects on these parameters in newborn rats. CONCLUSIONS In a rat model of maternal PCOS, exposure to androgens in utero resulted in dysbiosis of the intestinal microbiota and metabolic disorders of the newborn female rats.

BACKGROUND This study aimed to investigate the molecular mechanisms associated with the effects of propofol in a rat model of pain due to inflammation following subcutaneous injection with complete Freund's adjuvant (CFA). MATERIAL AND METHODS Sprague-Dawley rats were injected subcutaneously in the paw with CFA. Propofol or saline was administered by tail vein injection. After CFA treatment for 0 hours, 4 hours, 1 day, 4 days, 7 days, and 14 days, the behavior of the rats was assessed. An enzyme-linked immunosorbent assay (ELISA) measured serum levels of proinflammatory cytokines, including tumor necrosis factor (TNF)-alpha, interleukin (IL)-1s, and IL-6. Western blot and the quantitative reverse-transcription polymerase chain reaction (qRT-PCR) were used to detect levels of p38MAPK and NF-kappaB related mRNA and proteins, including p-p38, p38, p65, p-p65, NOD-like receptor family protein 3 (NLRP3), apoptosis-associated speck-like protein (ASC) and caspase-1 in rat spinal cord tissues. RESULTS Injection of CFA significantly reduced the mechanical withdrawal threshold (MWT), thermal withdrawal latency (TWL), and frequency responses to cold stimulation. Propofol treatment significantly reduced serum levels of TNF-alpha, IL-1s, and IL-6. Protein expression levels of p-p38 and p-p65 were upregulated in the rat model, which were inhibited by propofol treatment. CFA injection increased the expression levels of NLRP3, ASC, and caspase-1 in the spinal cord tissues of rats, which were reduced by propofol treatment. CONCLUSIONS In a rat model of pain following subcutanous injection with CFA, propofol reduced CFA-induced pain and inhibited the inflammatory response through the p38MAPK-nuclear factor-kappaB (NF-kappaB) pathway and the NLRP3 inflammasome.

BACKGROUND Preclinical and clinical studies have shown that the extract of Cynanchum paniculatum (bunge) kitag and the fukeqianjin formulation have beneficial effects in pelvic inflammatory disease (PID). This study aimed to compare the effects of Cynanchum paniculatum and fukeqianjin with a new decoction, xiaoyuningkun, consisting of Melia toosendan, Angelica biserrata, and Cynanchum paniculatum, in a mouse model of PID. MATERIAL AND METHODS The mouse model of PID included injection of the upper genital tract with hydrochloric acid (HCl) and lipopolysaccharide (LPS). The control group underwent sham treatment with 0.9% physiological saline. Cynanchum paniculatum, fukeqianjin, and xiaoyuningkun decoction were administered orally for 15 days. Acetic acid-induced writhing and thermal nociception hot plate tests evaluated the analgesic effects of treatment. Mouse uterus and Fallopian tubes were examined histologically to evaluate the degree of inflammation. Immunohistochemistry was used to measure the protein expression of intercellular adhesion molecule-1 (ICAM-1) and vascular endothelial growth factor (VEGF). Enzyme-linked immunosorbent assay (ELISA) measured serum levels of inflammatory cytokines. RESULTS Treatment with xiaoyuningkun decoction significantly reduced the pain threshold in the mouse model of PID and the degree of inflammation in the uterus and Fallopian tubes compared with Cynanchum paniculatum and fukeqianjin. Cynanchum paniculatum decoction significantly reduced the serum levels of interleukin-1ß (IL-1ß), tumor necrosis factor-alpha (TNF-alpha), ICAM-1, and VEGF, and the expression of ICAM-1 and VEGF in the mouse uterus and Fallopian tubes. CONCLUSIONS The new xiaoyuningkun decoction had analgesic and anti-inflammatory effects in the mouse model of PID, possibly by inhibiting ICAM-1, VEGF, and inflammatory cytokines.

BACKGROUND Oxidative stress and neuroinflammation are 2 pivotal mechanisms in the progression of cerebral ischemia/reperfusion injury. Biochanin A, a natural phytoestrogen, has been reported to protect against ischemic brain injury in animal experiments, but the possible pharmacological mechanisms of its neuroprotection remain elusive. In this research, we sought to investigate the neuroprotective effects of biochanin A in experimental stroke rats and the probable mechanisms underlying oxidative stress and inflammation signaling pathways. MATERIAL AND METHODS An ischemic stroke model was induced by inserting thread into the middle cerebral artery. Rats were pre-administered intraperitoneally with a vehicle solution or biochanin A (10, 20, or 40 mg·kg·d--⁻¹) for 14 days prior to ischemic stroke. Neurological score, infarct volume, and cerebral edema were assessed after 2 h of ischemia and 24 h of reperfusion. The activities of SOD and GSH-Px and MDA content were measured. The expressions of Nrf2, HO-1, and NF-kappaB and the activity of phosphor-IkappaBalpha were detected by Western blotting. RESULTS Biochanin A pretreatment significantly improved neurological deficit and decreased infarct size and brain edema. Biochanin A also enhanced SOD and GSH-Px activities and suppressed the production of MDA. Additionally, biochanin A promoted Nrf2 nuclear translocation, promoted the expression of HO-1, and inhibited NF-kappaB activation in ischemic brain injury. CONCLUSIONS The results indicated that biochanin A protected the brain against ischemic injury in rats by anti-oxidative and anti-inflammatory actions. The activation of the Nrf2 pathway and the inhibition of the NF-kappaB pathway may contribute to the neuroprotective effects of biochanin A.

BACKGROUND Cardiac dysfunction during endotoxemia is a major cause of cardiovascular disease with high morbidity and mortality. Alisol B 23-acetate (AB23A) is a triterpenoid extracted from the Rhizoma Alismatis, a kind of traditional Chinese medicine, exhibits anti-inflammatory activity on endotoxemia. This investigation aimed to uncover the protective effects of AB23A against sepsis-induced cardiac dysfunction. MATERIAL AND METHODS Adult male C57BL/6 mice received lipopolysaccharide (LPS) (20 mg/kg intravenous) stimulation, with or without pre-treatment of AB23A (10 mg/kg, 20 mg/kg, or 40 mg/kg). Histopathological staining and cardiac function were performed 4 hours after LPS stimulation. Then the levels of interleukin (IL)-6, IL-1ß, and tumor necrosis factor (TNF)-alpha were monitored with enzyme-linked immunosorbent assay (ELISA). In addition, H9C2 cells were treated with LPS (5 μg/mL) with or without pre-treated with AB23A (0.1 μM, 1 μM, or 10 μM), and the production of reactive oxygen species (ROS) was detected by DCFH-DA combined with flow cytometry. The expression of Toll-like receptor 4 (TLR4), NADPH oxidase 2 (NOX2), NOX4, P38, p-P38, extracellular-signal-regulated kinase (ERK), and p-ERK were assessed by western blotting. RESULTS AB23A improved the survival rate and ameliorated myocardial injury, decreased inflammatory infiltration and the level of IL-6, IL-1ß, and TNF-alpha in the LPS-stimulated mouse model. Moreover, AB23A inhibited the ROS production in LPS-treated H9C2 cells. In addition, AB23A suppressed the levels of TLR4 and NOX2 as well as the activation levels of P38 and ERK both in vivo and in vitro. CONCLUSIONS AB23A reduced LPS-induced myocardial dysfunction by inhibiting inflammation and ROS production through the TLR4/NOX2 pathway.

BACKGROUND This study aimed to develop a nude mouse model of orthotopic liver transplantation of HCCLM3 human hepatocellular carcinoma (HCC) cell xenografts and the use of imaging and histology to evaluate tumor development and progression. MATERIAL AND METHODS HCCLM3 cells were injected subcutaneously into 25 healthy male athymic BALB/c (nu/nu) nude mice. The tumors that developed were transplanted into the liver of a new set of nude mice. After four weeks and six weeks, the mice were imaged using ultrasound (US), software-assisted contrast-enhanced ultrasound (CEUS), fluorodeoxyglucose-positron emission tomography (FDG-PET). Histology was performed on the liver and liver tumors, and included immunohistochemistry for vascular endothelial growth factor (VEGF), CD31, CD34, and alpha-smooth muscle actin (alpha-SMA). RESULTS The success rate for orthotopic tumor transplantation in the mouse liver was 90% (18/20). Liver tumors measured 11.8±2.6 mm in diameter and 525.9±250.8 mm3 in volume on the sixth week. CEUS showed rapid wash-in and washout in the liver tumors, and PET showed low tumor cell metabolism. Bone metastases were present in 45% (9/20) of mice in the sixth week. Immunohistochemistry showed positive expression for VEGF, CD31, CD34, and alpha-SMA. CONCLUSIONS The nude mouse orthotopic liver transplantation model of human HCC was shown to be a reliable model that has the potential for future research on the pathogenesis and progression of HCC and studies on drug development.

BACKGROUND Depression is a major mood disorder. Some patients have been reported to improve following acupuncture. This study aimed to investigate the effects of acupuncture on behaviors associated with depression in the chronic unpredictable mild stress (CUMS) rat model. The expression of signaling pathway components of nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) in the rat hippocampus and plasma were also measured. MATERIAL AND METHODS Male Sprague-Dawley rats (N=40) were divided into the control group (N=10), the model group (N=10), the acupuncture group (N=10), and the non-acupuncture group (N=10). The rat model was established by orphaning combined with chronic unpredictable mild stress (CUMS) for six weeks. The acupuncture group was given 21 days of treatment using acupoints (AP) or non-acupoints (NP). Rat behaviors associated with depression were tested using the sucrose preference test (SPT), the open field test (OFT), and the elevated plus maze (EPM) test. Enzyme-linked immunoassay (ELISA) and reverse transcription-polymerase chain reaction (RT-PCR) were used to detect the expression of inducible nitric oxide synthase (iNOS), neuronal nitric oxide synthase (nNOS), and the N-methyl-D-aspartate (NMDA) receptor subunits, NR1, NR2A, and NR2B in the rat plasma and hippocampus. RESULTS Acupuncture reversed the behaviors associated with depression in the CUMS rat model and reduced the expression of components of the NO and cGMP pathway in the rat hippocampus and plasma. CONCLUSIONS In the CUMS rat model, treatment with acupuncture reduced behaviors associated with depression, and these effects were associated with changes in the NO and cGMP signaling pathway.

BACKGROUND It is thought that immunosuppressive treatment, besides anti-rejection properties, leads to pathological changes within the organ due to activation of mechanisms associated with oxidative stress. The aim of this study was to examine the parameters of oxidative stress in the livers of rats treated with the most commonly used transplant recipient drug regimens. MATERIAL AND METHODS The rat livers were obtained from archival material obtained from the previously performed experiment. Malondialdehyde (MDA), reduced glutathione (GSH) concentrations, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities were analyzed. RESULTS Only the group treated with tacrolimus (T), mycophenolate mofetil (M), and prednisone (P), the TMP group, showed a slight increase in lipid peroxide concentration compared to the control group, though the difference was not statistically significant. Comparison of lipid peroxide concentration between the other treatment combinations and the control group showed a significant decrease. Additionally, a difference in lipid peroxide concentrations in the livers was observed between the cyclosporine A (C) group and tacrolimus (T) group. Alterations of other oxidative stress parameters were also observed in different regimens. CONCLUSIONS Long-lasting immunosuppressive treatment does indeed affect redox status; however, the antioxidant defenses of the liver against the effects of excess hydrogen peroxide are efficient, so the superoxide dismutase/glutathione peroxidase (SOD/GPx) and superoxide dismutase/catalase (SOD/CAT) ratios were not significant.

Objective This study aims to evaluate the healing process of autografted mandibular bone defects in rats treated with zoledronate (ZOL). Subjects and methods A total of 180 Wistar rats were divided into four groups: group L received intravenous infusion of two doses of 0.06 mg/kg ZOL, nine weeks apart; group H received 0.06 mg/kg ZOL, while groups C and NC received normal saline at three-week intervals for nine weeks. Three weeks following the last infusion, a unilateral mandibular bone defect (5 mm) was created. Except in the NC group, all defects were repaired with autologous iliac bone graft. Fifteen animals from each group were sacrificed on postoperative Day 20, Day 40, and Day 60. Graft healing was scored using a histological grading system (ranging from 1 to 6). Results Histological evaluations performed on postoperative Day 60 showed that the mandibular defects were mainly repaired with fibrous tissue in the NC and H groups (93.00% ± 7.51% and 82.67% ± 13.08%, respectively) and with bone in the C and L groups (75.33% ± 14.20% and 92.67% ± 8.84%, respectively). The percentage of fibrous tissue and bone as well as the healing score of the NC and H groups were significantly different (P = 0.001) from those of the C and L groups. However, these were not different between neither the NC and H groups nor the C and L groups. Conclusion Based on the results of the present study the hypothesis can be established that there also might be a dose-dependent effect of ZOL on the healing of bone grafts in humans. This hypothesis has to be verified or rejected in clinical trials.

BACKGROUND Spinal cord injury (SCI) is a severe devastating condition associated with serious disability and neurologic deficits. Aberrant micro RNA (miRNA) expression has been related to a variety of central nervous system diseases including SCI. In the present study, we aimed to discover the role of miR-129-5p on SCI. MATERIAL AND METHODS An acute SCI rat model was induced, following the modified Allen method. A total of 36 rats were randomly assigned into 4 groups (n=9 in every group): Sham group; Model group (SCI+saline); SCI+NC group; and SCI+miR-129-5p group (100 nm solution, every 2 days). Basso-Beattie-Bresnahan (BBB) locomotor rating score was carried out to determine functional recovery. TUNEL (terminal dUTP nick-end labeling) staining was used to evaluate cell apoptosis. Hematoxylin and eosin staining was performed to assess the pathological state of spinal cord. Furthermore, western blot assay was conducted to measure the calpain1 and calpain2 expression. RESULTS Our data suggested that the expression level of miR-129-5p was markedly reduced in rats after SCI. Then miR-129-5p mimic was injected into the vertebral canal. We found that the SCI+miR-129-5p group had a high score in the BBB test compared with the SCI+NC group and the Model group. The overexpression of miR-129-5p obviously reduced tissue loss, damaged cells, and the number of TUNEL positive cells. Moreover, western blot assay exhibited that overexpression of miR-129-5p decreased calpain1, calpain2, and cleaved caspase-3 expression. CONCLUSIONS Our findings suggested that overexpression of miR-129-5p improved neurological function by promoting functional recovery, reducing tissue loss and cell apoptosis in rats in an SCI model, possibly through downregulation of calpain1 and calpain2.

BACKGROUND This study identified microRNAs (miRNAs) and mRNAs associated with Compound Longmaining (CLMN) treatment of acute myocardial infarction (AMI). Our results provide a theoretical framework to guide AMI treatment and improve myocardial injury. MATERIAL AND METHODS The myocardial tissues of the sham operation group (S), the model group (M), and the CLMN treatment group (T) were obtained. The mRNA and miRNA expression profiles were identified using RNA-sequencing analysis. The sequencing results were verified by quantitative real-time PCR (qRT-PCR). Bioinformatics was used to predict the function of differentially expressed genes (DEGs) and related signal transduction pathways. The target genes of miRNAs were predicted by software analysis, and the relationship between miRNA and mRNA was studied by network analysis. RESULTS RNA-sequencing revealed 22 differentially expressed miRNAs (DEMs) and 76 DEGs in myocardial tissue. Six DEMs and 9 DEGs were randomly selected for qRT-PCR validation, and corroborating results were obtained. The results of Gene ontology (GO) showed that DEGs participated in different biological processes. Through the combined analysis of miRNAs and mRNAs expression, it was confirmed that a single miRNA is involved in the regulation of multiple genes, and also multiple miRNAs can target one gene. CONCLUSIONS The analysis based on the miRNA-mRNA network can not only help to elucidate the potential molecular mechanism of CLMN treatment of AMI, but can also help in identifying novel therapeutic targets.

BACKGROUND Gegen qinlian decoction (GGQLD) is a form of traditional Chinese medicine used for hundreds of years for its efficacy in treating diabetes. However, the mechanisms underlying the therapeutic effects of GGQLD on diabetes are still not clear. We aimed to evaluate the effect of GGQLD on hepatic insulin resistance (IR) through silent information regulator1 (SIRT1)/forkhead box O1 (FOXO1) in an IR mouse model. MATERIAL AND METHODS A high-fat diet (HFD) mouse model was established and GGQLD was administrated by oral gavage. Metabolic parameters were detected, including body weights, triglyceride, fasting glucose, fasting insulin and HOMA-IR index, glucose intolerance, and insulin resistance. HE-stained sections were used to observe the histopathology of liver tissue. For in vitro study, GGQLD-medicated serum was used to treat palmitic acid-stimulated HepG2 cells. The glycogen synthesis and downstream SIRT1/FOXO1 signaling pathways were examined. Specific siRNAs were used to knock down SIRT1 in HepG2 cells. RESULTS GGQLD administration significantly decreased body weights, triglyceride level, fasting glucose level, fasting insulin level, and HOMA-IR index, and improved IR in HFD mice. GGQLD enhanced SIRT1 expression and suppressed the expression of Ac-FOXO1 in liver tissues. Further, GGQLD-medicated serum promoted SIRT1 upregulation and suppressed Ac-FOXO1 levels in palmitate-stimulated HepG2 cells. GGQLD-medicated serum also increased the protein expression of PPARγ and reduced the expression of FABP4 in palmitate-stimulated HepG2 cells. CONCLUSIONS We found that GGQLD alleviates insulin resistance through SIRT1-dependent deacetylation of FOXO1.

BACKGROUND Renal stones are the accumulated or deposited crystals that form and appear in supersaturated urine. This study aimed to the investigate the therapeutic effects of Huashi Pill on clearance of renal stones. MATERIAL AND METHODS Sprague Dawley rats were divided into normal control, positive control, low-dosage Huashi Pill, medium-dosage Huashi Pill, and high-dosage Huashi Pill groups. A renal rat model was established by using ethylene glycol, ammonium chloride, and calcium gluconate. The urinary pH, urine protein, and uric acid levels, as well as the calcium, magnesium, and phosphorus levels were examined. The blood urea nitrogen (BUN) and creatinine (Cr) levels were also evaluated. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin (TBIL) levels were evaluated. Crystal formation and calcium deposits were examined using hematoxylin and eosin (H and E) staining and von Kossa staining, respectively. Osteopontin (OPN) expression was evaluated with quantitative real-time polymerase chain reaction assay and immunohistochemical assay. RESULTS A renal stone rat model was successfully established. Huashi Pill significantly improved water and food intake and enhanced pH value of urine (P

Objectives This study investigated the biomechanical performance of decellularized porcine superflexor tendon (pSFT) grafts of varying diameters when utilized in conjunction with contemporary ACL graft fixation systems. This aimed to produce a range of ‘off-the-shelf’ products with predictable mechanical performance, depending on the individual requirements of the patient. Methods Decellularized pSFTs were prepared to create double-bundle grafts of 7 mm, 8 mm, and 9 mm diameter. Femoral and tibial fixation systems were simulated utilizing Arthrex suspension devices and interference screws in bovine bone, respectively. Dynamic stiffness and creep were measured, followed by ramp to failure from which linear stiffness and load at failure were measured. The mechanisms of failure were also recorded. Results Dynamic stiffness was found to increase with greater graft diameter, with significant differences between all groups. Conversely, dynamic creep reduced with increasing graft diameter with significant differences between the 7 mm and 9 mm groups and the 8 mm and 9 mm groups. Significant differences were also found between the 7 mm, 8 mm, and 9 mm groups for linear stiffness, but no significant differences were found between groups for load at failure. The distribution of failure mechanisms was found to change with graft diameter. Conclusion This study showed that decellularized pSFTs demonstrate comparable biomechanical properties to other ACL graft options and are a potentially viable option for ACL reconstruction. Although grafts can be stratified by their diameter to provide varying biomechanical properties, it may be more appropriate to alter the fixation technique to stratify for a greater diversity of biomechanical requirements. Cite this article: Bone Joint Res 2019;8:518–525.

BACKGROUND Several factors found in foods are beneficial to human health and they may contribute to radiation protection. Taking food factors could be an easy way to reduce the effects of radiation after nuclear accidents, as well as secondary radiation risks after cancer radiotherapy or space missions. Here, diallyl disulfide (DADS), a component of garlic oil, was studied for its ability to mitigate radiation damage. MATERIAL AND METHODS We investigated the effects of DADS on micronucleus (MN) formation and apoptosis in HepG2 cells by use of 4-Gy X-ray irradiation. We also assessed the effects of DADS on radiation damage in vivo by evaluating MN formation in bone marrow cells in mice (BALB/c, 8-week-old females) after oral intake of DADS prior to irradiation with 4 Gy. Several tissue effects were also investigated. RESULTS The presence of DADS inhibited MN formation, whereas DADS had no influence on the radiation-induced inhibition of cell cycle progression in HepG2 cells. An increase in apoptosis in HepG2 cells was induced after irradiation, and this effect was stronger in the presence of DADS than in its absence. In mice, when DADS was administered daily for 3 days prior to irradiation, MN formation in irradiated mice was decreased. The decrease in MN formation in mice was greater with 0.5% DADS compared to 1% DADS. Moreover, an increase in spleen weight observed 3 weeks after irradiation was suppressed in mice administered DADS. CONCLUSIONS DADS is a potential radiation-protective agent that effectively mitigates DNA damage, and its effects in the spleen observed after irradiation may be related to inflammation and carcinogenesis.

BACKGROUND Nanotechnology is one of the most productive approaches for specifically delivering drug payloads to the region of interest to decrease nonspecific distribution and unwanted toxicities. MATERIAL AND METHODS We prepared glycol chitosan stearate self-assembled nanoparticles loaded with methotrexate (MTX) for NF-kappaB targeting in treatment of rheumatoid arthritis (RA). The nanoparticles were prepared using hydrophobic modification of glycol chitosan (GC) with steric acid (SA) and was characterized using IR. The efficiency of nanoparticles after their physiochemical characterization was measured in vitro and by in vivo studies in mice. RESULTS The nanoparticles thus prepared were spherical in shape, 235 nm in diameter, and had negative zeta potential. The entrapment efficiency of MTX-GC-SA was more than 70%. The in vitro higher uptake of MTX-GC-SA in murine macrophage cells (RAW 264.7) was confirmed using confocal microscopy and FACS analysis. Systemic administration of MTX-GC-SA into collagen-induced arthritis (CIA) mice resulted in high accumulation in inflamed joints. The MTX-GS-SA revealed significantly better therapeutic efficacy against CIA mice compared to free MTX. CONCLUSIONS These findings highlight the potential of using this MTX-GC-SA nanoparticle formulation in suppressing inflammatory arthritis for effective treatment of RA.

Objective: The aim of this study was to investigate the effects of human amniotic membrane (HAM) on fracture healing in an animal model. Methods: Standard tibial diaphysial fractures were created in twenty-eight Wistar-Albino rats and treated with intramedullary Kirschner wire (K-wire) and HAM (HAM (+) group) or K-wire only (HAM (–) group). Fracture healing was evaluated by histological analysis, radiologic X-ray views and callus diameter measurements at 3rd and 6th weeks postoperatively. Results: Fracture healing was histologically better in the HAM (+) group and the difference was statistically significant at both 3rd and 6th weeks postoperatively (p

Several methods are used for periodontal regeneration and alveolar ridge reconstruction. This study aimed to compare the bone regeneration capacities of MinerOss X, Bio-Oss, and autograft in rabbit calvaria. In this animal study, four defects measuring 8 mm in diameter were created in the calvaria of 10 rabbits using a trephine bur. Three defects were randomly filled with MinerOss X, Bio-Oss, and autogenous bone. The fourth defect remained empty as a control. The rabbits were sacrificed after 4 or 8 weeks. Calvarial samples were taken and histopathologically evaluated. The mean number of osteoblasts and the amount of newly formed bone in all groups were higher at 8 compared to 4 weeks. At 4 and 8 weeks, the amount of newly formed bone and number of osteoblasts and osteocytes in MinerOss X group were significantly greater than the corresponding values in other groups, and MinerOss X was superior to Bio-Oss and autograft in all the assessed variables at both 4 and 8 weeks (P < .001). Within the limitations of this study, the results showed that the number of osteoblasts and osteocytes and the amount of newly formed bone in the MinerOss X group were higher than those in Bio-Oss and autograft groups. However, further clinical studies are warranted.