Biomechanical and histological evaluation of aspirin in rotator cuff tear rat model.

Background: Aspirin is a representative non-steroidal anti-inflammatory drug (NSAIDs) and has been commonly used for the treatment of tendinopathy in clinical practice. In this study, we aimed to evaluate the biomechanical and histological healing effects of aspirin on the healing of the tendon-to-bone interface after rotator cuff tear repair. Methods: A total of 20 male Sprague-Dawley rats were randomly divided into two groups of 10 rats each. Group-C performed repaironly, and group-aspirin treated with aspirin after tendon repair. Group-aspirin rat were intraperitoneally injected with aspirin at 10 mg/kg every 24 h for 7 days. Eight weeks after surgery, the left shoulder of each rat was used for histological analysis and the right shoulder for biomechanical analysis. Results: In the biomechanical analysis, there was no significant difference in load-to-failure (group-C: 0.61 ± 0.32 N, group-aspirin: 0.74 ± 0.91 N; p = .697) and ultimate stress (group-C: 0.05 ± 0.01 MPa, group-aspirin: 0.29 ± 0.43 MPa; p = .095). For the elongation (group-C: 222.62 ± 57.98%, group-aspirin: 194.75 ± 75.16%; p = .028), group-aspirin confirmed a lower elongation level than group-C. In the histological evaluation, the Bonar score confirmed significant differences in collagen fiber density (group-C: 1.60 ± 0.52, group-aspirin: 2.60 ± 0.52, p = .001) and vascularity (group-C: 1.00 ± 0.47, group-aspirin: 2.20 ± 0.63, p = .001) between the groups. Conclusions: Aspirin injection after rotator cuff tear repair may enhance the healing effect during the early remodeling phase of tendon healing.

Omaveloxolone Ameliorates Cognitive Deficits by Inhibiting Apoptosis and Neuroinflammation in APP/PS1 Mice.

Alzheimer's disease (AD) is the most prevalent neurodegenerative disease associated with aging, characterized by progressive cognitive impairment and memory loss. However, treatments that delay AD progression or improve its symptoms remain limited. The aim of the present study was to investigate the therapeutic effects of omaveloxolone (Omav) on AD and to explore the underlying mechanisms. Thirty-week-old APP/PS1 mice were selected as an experimental model of AD. The spatial learning and memory abilities were tested using the Morris water maze. Amyloid-beta (Aß) deposition in the brains was measured using immunohistochemistry. Network pharmacological analyses and molecular docking were conducted to gain insights into the therapeutic mechanisms of Omav. Finally, validation analyses were conducted to detect changes in the associated pathways and proteins. Our finding revealed that Omav markedly rescued cognitive dysfunction and reduced Aß deposition in the brains of APP/PS1 mice. Network pharmacological analysis identified 112 intersecting genes, with CASP3 and MTOR emerging as the key targets. In vivo validation experiments indicated that Omav attenuated neuronal apoptosis by regulating apoptotic proteins, including caspase 3, Bax, and Bcl-2. Moreover, Omav suppressed neuroinflammation and induced autophagy by inhibiting the phosphorylation of mTOR. These findings highlight the therapeutic efficacy of Omav in AD and that its neuroprotective effects were associated with inhibiting neuronal apoptosis and regulating neuroinflammation.

Strategy for Designing In Vivo Dose-Response Comparison Studies.

In preclinical drug discovery, at the step of lead optimization of a compound, in vivo experimentation can differentiate several compounds in terms of efficacy and potency in a biological system of whole living organisms. For the lead optimization study, it may be desirable to implement a dose-response design so that compound comparisons can be made from nonlinear curves fitted to the data. A dose-response design requires more thought relative to a simpler study design, needing parameters for the number of doses, the dose values, and the sample size per dose. This tutorial illustrates how to calculate statistical power, choose doses, and determine sample size per dose for a comparison of two or more dose-response curves for a future in vivo study.

Cai's herbal tea enhances mitochondrial autophagy of type 1 diabetic mellitus ß cells through the AMPK/mTOR pathway and alleviates inflammatory response.

BACKGROUND: This study investigates the therapeutic mechanisms of Cai's Herbal Tea in Type 1 Diabetes Mellitus (T1DM) mice, focusing on its effects on mitochondrial change and autophagy via the AMP-activated protein kinase (AMPK)-mammalian target of rapamycin (mTOR) pathway. METHODS: The composition of Cai's Herbal Tea was analyzed by Ultra-High Performance Liquid Chromatography-Quadrupole Time of Flight Mass Spectrometry (UHPLC-Q/TOF-MS). C57BL/6 mice and Min6 pancreatic beta cells were divided into control, diabetic mellitus (DM)/high glucose (HG), and treatment groups (low, medium, and high doses of Cai's Tea, and Metformin). Key physiological parameters, pancreatic islet health, Min6 cell morphology, viability, and insulin (INS) secretion were assessed. Small Interfering RNA-AMPK (si-AMPK) was utilized to confirm the pathway involvement. RESULTS: Cai's Herbal Tea improved body weight, pancreatic islet pathological injury, and INS secretion whereas reduced total triglycerides, fasting blood sugar, and Interferon gamma (INF-γ) in T1DM mice, particularly at higher doses. In Min6 cells, Cai's Tea mitigated HG-induced damage and proinflammatory response, enhancing cell viability and INS secretion. Notably, it reduced swelling and improved cristae structure in treated groups of mitochondria and promoted autophagy via the AMPK-mTOR pathway, evidenced by increased LC3II/LC3I and P-AMPK/AMPK ratios, and decreased P-mTOR/mTOR and P62 expressions in pancreatic islet ß-cells. Furthermore, these effects were converted by si-AMPK interference. CONCLUSION: Cai's Herbal Tea exhibits significant therapeutic efficacy in T1DM mice by improving mitochondrial health and inducing autophagy through the AMPK-mTOR pathway in pancreatic islet ß-cells. These findings highlight its potential as a therapeutic approach for T1DM management.

Histological response of inflamed pulp to hydraulic calcium silicate cements in direct pulp capping: Systematic review of pulpitis models.

This systematic review aimed to compare the histological response of inflamed pulpodentinal complex to the hydraulic calcium silicate cements in experimental animal models of pulpitis. Articles that evaluated the histological response of inflamed pulp to mineral trioxide aggregate (MTA) in comparison with other restorative materials were selected and analysed in detail. The risk of bias assessment was conducted using SYRCLE's RoB tool. The GRADEpro tool was used to determine the overall quality of evidence. Out of the 2947 retrieved articles from databases, five articles fulfilled the inclusion criteria. MTA induced significantly more hard tissue formation compared to calcium hydroxide. The use of pulp-capping material containing fluocinolone acetonide and ASP/PLGA-ASP/ACP/PLLA-PLGA composite membrane was comparable. This systematic review could not demonstrate enhanced efficiency of capping materials compared to MTA. Future well-conducted animal studies are warranted for demonstrating the hard tissue formation abilities of pulp-capping materials with convenient inflammatory conditions.

Influence of physicochemical characteristics of calcium phosphate-based biomaterials in cranio-maxillofacial bone regeneration. A systematic literature review and meta-analysis of preclinical models.

Objectives: Calcium phosphate-based biomaterials (CaP) are the most widely used biomaterials to enhance bone regeneration in the treatment of alveolar bone deficiencies, cranio-maxillofacial and periodontal infrabony defects, with positive preclinical and clinical results reported. This systematic review aimed to assess the influence of the physicochemical properties of CaP biomaterials on the performance of bone regeneration in preclinical animal models. Methods: The PubMed, EMBASE and Web of Science databases were searched to retrieve the preclinical studies investigating physicochemical characteristics of CaP biomaterials. The studies were screened for inclusion based on intervention (physicochemical characterization and in vivo evaluation) and reported measurable outcomes. Results: A total of 1532 articles were retrieved and 58 studies were ultimately included in the systematic review. A wide range of physicochemical characteristics of CaP biomaterials was found to be assessed in the included studies. Despite a high degree of heterogeneity, the meta-analysis was performed on 39 studies and evidenced significant effects of biomaterial characteristics on their bone regeneration outcomes. The study specifically showed that macropore size, Ca/P ratio, and compressive strength exerted significant influence on the formation of newly regenerated bone. Moreover, factors such as particle size, Ca/P ratio, and surface area were found to impact bone-to-material contact during the regeneration process. In terms of biodegradability, the amount of residual graft was determined by macropore size, particle size, and compressive strength. Conclusion: The systematic review showed that the physicochemical characteristics of CaP biomaterials are highly determining for scaffold's performance, emphasizing its usefulness in designing the next generation of bone scaffolds to target higher rates of regeneration.

Characterization of Gut Microbiota in Rats and Rhesus Monkeys After Methamphetamine Self-administration.

Methamphetamine (MA) is one of the most abused drugs globally, but the mechanism of its addiction remains unclear. Several animal studies have shown that the gut microbiota (GM) influences addictive behaviors, but the pattern of GM changes during addiction in animals of different species remains unclear. The aim of this study was to explore the association between dynamic changes in GM and MA self-administration acquisition among two classical mammals, rhesus monkeys (Macaca mulatta) and rats, MA self-administration models. Male Sprague-Dawley rats and male rhesus monkeys were subjected to classical MA self-administration training, and fecal samples were collected before and after MA self-administration training, respectively. 16S rRNA sequencing was used for GM analyses. We found that GM changes were more pronounced in rats than in rhesus monkeys, as evidenced by more GM taxa producing significant differences before and after MA self-administration training in rats than in monkeys. We also found that the expression of the genus Clostridia_vadinBB60_group significantly decreased after MA self-administration training in both rats and rhesus monkeys. Lactobacillus changes were significantly negatively correlated with total MA uptake in rats (Pearson R = - 0.666, p = 0.035; Spearman R = - 0.721, p = 0.023), whereas its change was also highly negatively correlated with total MA uptake in rhesus monkeys (Pearson R = - 0.882, p = 0.118; Spearman R = - 1.000, p = 0.083), although this was not significant. These findings suggest that MA causes significant alterations in GM in both rhesus monkeys and rats and that the genus Lactobacillus might be a common therapeutic target for MA uptake prevention across the species.

Clinical efficacy and performance evaluation of a bendable remote robot system for a bone tumour surgery: A pilot animal study.

BACKGROUND: Traditional open surgery for bone tumours sometimes has as a consequence an excessive removal of healthy bone tissue because of the limitations of rigid surgical instruments, increasing infection risk and recovery time. METHODS: We propose a remote robot with a 4.5-mm diameter bendable end-effector, offering four degrees of freedom for accessing the inside of the bone and performing tumour debridement. The preclinical studies evaluated the effectiveness, clinical scenario, and usability across 12 total surgeries-six phantom surgeries and six bovine bone surgeries. Evaluation criteria included skin incision size, bone window size, surgical time, removal rate, and conversion to open surgery. RESULTS: Preclinical studies demonstrated that the robotic approach requires significantly smaller incision size and procedure times than traditional open curettage. CONCLUSION: This study validated the performance of the proposed system by assessing its preclinical effectiveness and optimising surgical methods using human phantom and bovine bone tumour models.

Effects of Sapindus mukorossi Seed Oil on Bone Healing Efficiency: An Animal Study.

Natural products have attracted great interest in the development of tissue engineering. Recent studies have demonstrated that unsaturated fatty acids found in natural plant seed oil may exhibit positive osteogenic effects; however, few in vivo studies have focused on the use of plant seed oil for bone regeneration. The aim of this study is to investigate the effects of seed oil found in Sapindus mukorossi (S. mukorossi) on the osteogenic differentiation of mesenchymal stem cells and bone growth in artificial bone defects in vivo. In this study, Wharton-jelly-derived mesenchymal stem cells (WJMSCs) were co-cultured with S. mukorossi seed oil. Cellular osteogenic capacity was assessed using Alizarin Red S staining. Real-time PCR was carried out to evaluate ALP and OCN gene expression. The potential of S. mukorossi seed oil to enhance bone growth was assessed using an animal model. Four 6 mm circular defects were prepared at the parietal bone of New Zealand white rabbits. The defects were filled with hydrogel and hydrogel-S. mukorossi seed oil, respectively. Quantitative analysis of micro-computed tomography (Micro-CT) and histological images was conducted to compare differences in osteogenesis between oil-treated and untreated samples. Although our results showed no significant differences in viability between WJMSCs treated with and without S. mukorossi seed oil, under osteogenic conditions, S. mukorossi seed oil facilitated an increase in mineralized nodule secretion and upregulated the expression of ALP and OCN genes in the cells (p < 0.05). In the animal study, both micro-CT and histological evaluations revealed that new bone formation in artificial bone defects treated with S. mukorossi seed oil were nearly doubled compared to control defects (p < 0.05) after 4 weeks of healing. Based on these findings, it is reasonable to suggest that S. mukorossi seed oil holds promise as a potential candidate for enhancing bone healing efficiency in bone tissue engineering.

Elevated level of urinary tellurium is a potential risk for increase of blood pressure in humans and mice.

BACKGROUND: People worldwide are routinely exposed to tellurium mainly via dietary ingestion. There has been no study to clarify the contribution of tellurium to blood pressure in humans or animals. METHODS: In this cross-sectional study conducted in a general population of 2592 residents in Japan, the associations of urinary tellurium levels with blood pressure and prevalence of hypertension were investigated. The potential sources of tellurium were also investigated. An interventional study in mice confirmed the effect of tellurium exposure on blood pressure. RESULTS: Linear and logistic regression analyses with consideration of confounders including urinary sodium-potassium ratio showed significant positive associations of urinary tellurium level with prevalence of hypertension and blood pressure. Cereals/beans and vegetables/fruits were determined to be potential dietary sources of tellurium exposure. Intermediary analysis suggested that increased intake of cereals/beans, but not that of vegetables/fruits, is positively associated with the tellurium-mediated risk of hypertension. Correspondingly, the mouse study showed that exposure to a putative human-equivalent dose of tellurium via drinking water increased blood pressure with an elevated level of urinary tellurium. The temporally increased blood pressure was decreased to the normal level by a break of tellurium exposure with a reduced level of urinary tellurium. CONCLUSIONS: The interdisciplinary approach provided the first evidence that tellurium exposure is a potential risk for increase of blood pressure. Since the human urinary tellurium level in this study is comparable with the levels in general populations in other Asian and European countries in previous studies, exposure to tellurium may be a latent universal risk for hypertension.

Efficacy of bone ring grafts for the reconstruction of alveolar ridge deficiencies: a systematic review. Part II: animal trials.

Background: Bone ring (BR) grafts have been introduced to reconstruct alveolar ridge defects with simultaneous implant placement, but their clinical effectiveness remains undetermined. The aim of the current systematic review was to critically appraise evidence from animal studies regarding the effectiveness of BR grafts in alveolar ridge reconstruction and their variations under different surgical protocols. Methods: Electronic retrieval of six databases (MEDLINE, Embase, Cochrane Library, ScienceDirect, Web of Science, and Scopus) and citation search until 11 October 2023, for animal studies on bone augmentation employing BR grafts. The outcome variables were total bone area (BA), bone volume (BV), bone-implant contact (BIC), and histology. The protocol was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and prospectively registered with PROSPERO (CRD42023453949). Results: Ten studies were included in the qualitative analysis according to the screening criteria. Two studies demonstrated favorable bone remodeling and osseointegration of the BR with both the implant and pristine bone. A comparative study between autogenous BRs and allogenic BRs reported a higher percentage of BA and BIC at 4 months of healing, but conflicting data were observed at 8 months. Another study indicated a significant advantage of autogenous BRs over bovine and biphasic ceramic BRs in terms of BA and BIC after 5 weeks. Three studies found that using collagen membranes did not significantly affect BA, BV, or BIC when used simultaneously with autogenous BRs during implant placement. Two studies evaluated one-stage and two-stage implant placement in conjunction with BR grafts, revealing similar levels of BA, BV, and BIC except for differences in total treatment time. Furthermore, one study found that the use of mucogingival junction incision and split-thickness flap significantly reduced the incidence of wound dehiscence compared with conventional incision and flap. Conclusions: Vertical bone augmentation surgery utilizing BR grafts with one-stage implant placement yielded histological and histomorphometric outcomes comparable to those achieved with two-stage implant placement or the additional application of collagen membrane.

Assessing systemic, developmental, and reproductive toxicity and estrogenicity of Korean red ginseng extract G1899 in juvenile Sprague-Dawley Rats.

Background: Korean red ginseng (KRG) is a product from ginseng roots, which is enriched with ginsenosides and has been utilized for a long time as an adaptogen to alleviate various physiological or disease conditions. While KRG is generally considered safe, conducting a thorough toxicological assessment of the spray-dried powder G1899 during the juvenile period is essential to establish its safety profile. This study aimed to assess the safety of G1899 during the juvenile period using Sprague-Dawley rats. Methods: Two studies were conducted separately: a juvenile toxicity study and a uterotrophic bioassay. To assess the potential toxicity at systemic, postnatal developmental, and reproductive levels, G1899 was orally gavaged once a day in post-weaning juvenile Sprague-Dawley (SD) rats at 0, 1250, 2500, or 5000 mg/kg/day. Estrogenicity was assessed by orally gavaging G1899 in immature female SD rats at 0, 2500, or 5000 mg/kg/day on postnatal days (PND) 19-21, followed by a uterotrophic bioassay. These studies were conducted in accordance with the Good Laboratory Practice (GLP) regulations and regulatory test guidelines. Results: Regarding juvenile toxicity, no abnormalities related to the G1899 treatment were observed in any group during the experiment. Moreover, no uterotrophic responses were observed in the dosed female group. Based on these results, the no observed adverse effect level (NOAEL) of G1899 was determined to be at least 5000 mg/kg/day for general systemic function, developmental/reproductive function, and estrogenic activity. Conclusion: Our results suggest that G1899 is not toxic to juveniles at doses of up to 5000 mg/kg/day.

New Bone Growth into Surgical Bone Defects Grafted with a Novel Cultivated Coral Graft: A Histomorphometric Study in Rabbit Calvarias.

Natural Coral Particles (NCPs) are a suitable scaffold material for Guided Bone Regeneration (GBR) procedures; it combines the placement of a bone substitute supporting a barrier membrane. Due to increasing sea pollution and the declarations of endangered coral species (KYOTO 1997), they are no longer suitable for the medical industry. Novel domestic corals have been grown under controlled conditions to produce cultivated coral graft (CCG) material. This study aimed to evaluate a new CCG in an in vivo experimental GBR procedure. The calvarias of 8 rabbits were surgically exposed, and circular defects 8 mm in diameter were prepared. One defect was filled with CCG particles (experimental group); the contralateral defect (control group) was spontaneously filled by blood clot. The defects were covered with a collagen membrane. Animals were euthanized after 8 weeks. Histological observations of the defects showed similar bone growth patterns in both experimental and control osteotomies. In the experimental defects, no traces of coral particles were observed. Histometric analysis showed denser bone in the pristine zone (65-66%) than in the peripheral zone for both the control (50%) and experimental defects (31%) (P= NS). The new bone percentage was reduced from the peripheral zone toward the middle and the center of the defect (31%, 32% and 27%, respectively) as the distance from the peripheral pristine bone borders increased. The existing data support the complete degradation of CCG as space-maintaining scaffold for GBR procedures.

Prospect of Mesenchymal Stem Cells in Enhancing Nerve Regeneration in Brachial Plexus Injury in Animals: A Systematic Review.

Objectives: Brachial plexus injuries (BPI), although rare, often results in significant morbidity. Stem cell was thought to be one of BPI treatment modalities because of their nerve-forming regeneration potential. Although there is a possibility for the use of mesenchymal stem cells as one of BPI treatment, it is still limited on animal studies. Therefore, this systematic review aimed to analyze the role of mesenchymal stem cells in nerve regeneration in animal models of brachial plexus injury. Method: This study is a systematic review with PROSPERO registration number CRD4202128321. Literature searching was conducted using keywords experimental, animal, brachial plexus injury, mesenchymal stem cell implantation, clinical outcomes, electrophysiological outcomes, and histologic outcomes. Searches were performed in the PubMed, Scopus, and ScienceDirect databases. The risk of bias was assessed using SYRCLE's risk of bias tool for animal studies. The data obtained were described and in-depth analysis was performed. Result: Four studies were included in this study involving 183 animals from different species those are rats and rabbits. There was an increase in muscle weight and shortened initial onset time of muscle contraction in the group treated with stem cells. Electrophysiological results showed that mesenchymal stem cells exhibited higher (Compound muscle action potential) CMAP amplitude and shorter CMAP latency than control but not better than autograft. Histological outcomes showed an increase in axon density, axon number, and the formation of connections between nerve cells and target muscles. Conclusion: Mesenchymal stem cell implantation to animals with brachial plexus injury showed its ability to regenerate nerve cells as evidenced by clinical, electrophysiological, and histopathological results. However, this systematic study involved experimental animals from various species so that the results cannot be uniformed, and conclusion should be drawn cautiously.

Critical-sized marginal defects around implants in the rabbit mandible.

BACKGROUND: The mandible of the rabbit is considered a reliable model to be used to study bone regeneration in defects. The aim of the present study was to evaluate the formation of new bone around implants installed in defects of either 5 or 10 mm in the mandible of rabbits. MATERIALS AND METHODS: In 12 rabbits, 3 mm deep circumferential defect, either 5 or 10 mm in diameter, were prepared bilaterally and an implant was placed in the center. A collagen membrane was placed to close the entrance. After 10 weeks, biopsies were taken, histological slides were prepared, and different regions of the defects were analyzed. RESULTS: Similar amounts of new bone were found in both defects. However, most of the 5 mm defects were filled with new bone. New bone was observed closing the entrance of the defect and laid onto the implant surface. Only in a few cases the healing was incomplete. Despite a similar percentage of new bone found within the 10 mm defects, the healing was incomplete in most of the cases, presenting a low rate of bone formation onto the implant surface within the defect. Only one case presented the closure of the entrance. CONCLUSIONS: The dimensions of the defect strongly influenced the healing so that a circumferential marginal defect of 10 mm around an implant in the mandible body should be considered a critical-sized defect. The presence of the implant and of residues of teeth might have strongly influenced the healing.

Effects of moderate ethanol exposure on risk factors for cardiovascular disease and colorectal cancer in adult Wistar rats.

While past studies have provided evidence linking excessive alcohol consumption to increased risk for cardiovascular diseases (CVDs) and colorectal cancer (CRC), existing data on the effects of moderate alcohol use on these conditions have produced mixed results. The purpose of this study was to investigate the effects of moderate alcohol consumption on risk factors associated with the development of CVDs and CRC in adult rats. Twenty-four, 14-month-old, non-deprived male Wistar rats were randomly assigned to either an ethanol group, which consisted of voluntary access to a 20% (v/v) ethanol solution on alternate days, or a water control group (n = 12/group) for 13 weeks. Blood samples were collected to analyze levels of albumin, glucose, adiponectin, lipids, oxidized low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C), apolipoprotein A1 (apoA1), C-reactive protein (CRP), high-mobility group box 1 protein (HMGB-1), tumor necrosis factor-alpha (TNF-α), thyroxine, thyroid-stimulating hormone, 8-oxo-2'-deoxyguanosine (8-oxo-dG), liver function enzymes, and antioxidant capacity. Colonic gene expression related to colon carcinogenesis was also assessed. Ethanol-treated rats were found to have significantly higher HDL-C and apoA1 levels compared to controls. Moderate alcohol consumption led to significantly lower CRP levels and a trend for decrease in HMGB-1, TNF-α, and 8-oxo-dG levels. In the ethanol-exposed group, colonic gene expression of superoxide dismutase was upregulated while aldehyde dehydrogenase 2 showed a trend for increase compared to the control group. These results indicate that adopting a moderate approach to alcohol consumption could potentially improve health biomarkers related to CVD and CRC by increasing HDL-C levels and antioxidant activity and reducing DNA damage and inflammatory activity.

Hard tissue formation in pulpotomized primary teeth in dogs with nanomaterials MCM-48 and MCM-48/hydroxyapatite: an in vivo animal study.

BACKGROUND: This animal study sought to evaluate two novel nanomaterials for pulpotomy of primary teeth and assess the short-term pulpal response and hard tissue formation in dogs. The results were compared with mineral trioxide aggregate (MTA). METHODS: This in vivo animal study on dogs evaluated 48 primary premolar teeth of 4 mongrel female dogs the age of 6-8 weeks, randomly divided into four groups (n = 12). The teeth underwent complete pulpotomy under general anesthesia. The pulp tissue was capped with MCM-48, MCM-48/Hydroxyapatite (HA), MTA (positive control), and gutta-percha (negative control), and the teeth were restored with intermediate restorative material (IRM) paste and amalgam. After 4-6 weeks, the teeth were extracted and histologically analyzed to assess the pulpal response to the pulpotomy agent. RESULTS: The data were analyzed using the Kruskal‒Wallis, Fisher's exact, Spearman's, and Mann‒Whitney tests. The four groups were not significantly different regarding the severity of inflammation (P = 0.53), extent of inflammation (P = 0.72), necrosis (P = 0.361), severity of edema (P = 0.52), extent of edema (P = 0.06), or connective tissue formation (P = 0.064). A significant correlation was noted between the severity and extent of inflammation (r = 0.954, P < 0.001). The four groups were significantly different regarding the frequency of bone formation (P = 0.012), extent of connective tissue formation (P = 0.047), severity of congestion (P = 0.02), and extent of congestion (P = 0.01). No bone formation was noted in the gutta-percha group. The type of newly formed bone was not significantly different among the three experimental groups (P = 0.320). CONCLUSION: MCM-48 and MCM-48/HA are bioactive nanomaterials that may serve as alternatives for pulpotomy of primary teeth due to their ability to induce hard tissue formation. The MCM-48 and MCM-48/HA mesoporous silica nanomaterials have the potential to induce osteogenesis and tertiary (reparative) dentin formation.

Influence on marginal bone levels at implants equipped with blades aiming to control the lateral pressure on the cortical bone. An experimental study in dogs.

BACKGROUND: To avoid cortical compression, several implant systems have included in the protocol dedicated drills aimed at widening the cortical region of osteotomy. However, the manual execution of this operation does not guarantee the necessary precision. Hence, the present study aimed to determine the optimal size of the recipient site at the level of the alveolar crest in relation to the size of the coronal region of the implant to achieve the best healing result. MATERIALS AND METHODS: Blades of different diameters were incorporated into the coronal part of the implant to prepare the cortical region of the mandibular alveolar bone crest in different dimensions in relation to the collar of the implant. The differences in diameter of the blades in relation to the collar of the implant were as follows: one control group, -175 µm, and three test groups, 0 µm, + 50 µm, or + 200 µm. RESULTS: The marginal bone loss (MBL) at the buccal aspect was 0.7 mm, 0.5 mm, 0.2 mm, and 0.7 mm in the - 175 µm, 0.0 µm, + 50 µm, + 200 µm groups, respectively. The differences were statistically significant between group + 50 µm and control group - 175 µm (p = 0.019), and between + 50 µm and + 200 µm (p < 0.01) groups. The level of osseointegration at the buccal aspect was more coronally located in the test groups than in the control group, whereas the bone-to-implant contact percentage was higher in the + 50 µm and + 200 µm groups. However, these differences were not statistically significant. CONCLUSIONS: The lowest bone crest resorption and highest levels of osseointegration were observed in the 0.0 µm and + 50 µm groups. The cortical region where the blades had performed their cutting action showed regular healing with perfect hard and soft tissues sealing in all the groups. Cortical blades gathered bone particles, particularly in the + 200 µm group, which were incorporated into the newly formed bone. The results from the present experiment provide support to the use of blades that produce a marginal gap of 50 µm after implant insertion.

In vivo chronic scaffolding force of a resorbable magnesium scaffold.

The aim of this study is to qualitatively characterize the in vivo chronic scaffolding force of the Magmaris® Resorbable Magnesium Scaffold (RMS). This important parameter of scaffolds must be balanced between sufficient radial support during the healing period of the vessel and avoidance of long-term vessel caging. A finite element model was established using preclinical animal data and used to predict the device diameter and scaffolding force up to 90 days after implantation. To account for scaffold resorption, it included backbone degradation as well as formation of discontinuities as observed in vivo. The predictions of the model regarding acute recoil and chronic development of the device diameter were in good agreement with the preclinical data, supporting the validity of the model. It was found that after 28 and 90 days, the Magmaris® RMS retained 90 % and 47 % of its initial scaffolding force, respectively. The reduction in scaffolding force was mainly driven by discontinuities in the meandering segments. Finite element analysis combined with preclinical data is a reliable method to characterize the chronic scaffolding force.

Expression of erythropoietin receptor protein in the mouse hippocampus in response to normobaric hypoxia.

Background: Over the past decades, accumulating research on erythropoietin (EPO) and its receptor (EPOR) has revealed various neuroprotective actions and upregulation in hypoxic conditions. To our knowledge, EPOR protein levels in the hippocampus and isocortex have never been measured. Therefore, the aim of this study was to measure EPOR protein in the hippocampus (HPC) and prefrontal cortex (PFC). Further objectives were to examine the effects of exposure to normobaric hypoxia of various degrees and durations on EPOR protein and to explore how long-lasting these effects were. Method: Adult C57BL/6 mice were randomized into a control group (N = 12) or various hypoxia groups (N = 5-11). Mice were exposed to three different O2 concentrations (10 %, 12 %, or 18 %) for 8 h a day for 5 days and sacrificed immediately after the last exposure. The effect of exposure to 12 % O2 for 1 day and 4 weeks (8 h per day) at this survival time was also examined. Additionally, groups of mice were exposed to 12 % O2 for 1 or 5 days (8 h per day) and euthanized at various times (up to 3 weeks) thereafter to examine the duration of EPOR protein regulation in the HPC and the PFC. EPOR protein was detected with a sandwich-ELISA method. Results: EPOR protein was present in the HPC and PFC, at 206.64 ± 43.98 pg/mg and 184.25 ± 48.21 pg/mg, respectively. The highest increase in EPOR protein was observed in the HPC after 5 days of 8 h exposure to 12 % O2 and was most pronounced 24 h after last exposure. The effect of hypoxia normalized within one week after the last exposure. Conclusion: This study successfully measured hippocampal EPOR protein and showed a significant association between normobaric hypoxia and acute EPOR elevation. It is our hope that this study can provide guidance to future research on the neuroprotective effects of EPO.