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.

Effects of electrical stimulation with alternating fields on the osseointegration of titanium implants in the rabbit tibia - a pilot study.

Introduction: Electrical stimulation has been used as a promising approach in bone repair for several decades. However, the therapeutic use is hampered by inconsistent results due to a lack of standardized application protocols. Recently, electrical stimulation has been considered for the improvement of the osseointegration of dental and endoprosthetic implants. Methods: In a pilot study, the suitability of a specifically developed device for electrical stimulation in situ was assessed. Here, the impact of alternating electric fields on implant osseointegration was tested in a gap model using New Zealand White Rabbits. Stimulation parameters were transmitted to the device via a radio transceiver, thus allowing for real-time monitoring and, if required, variations of stimulation parameters. The effect of electrical stimulation on implant osseointegration was quantified by the bone-implant contact (BIC) assessed by histomorphometric (2D) and µCT (3D) analysis. Results: Direct stimulation with an alternating electric potential of 150 mV and 20 Hz for three times a day (45 min per unit) resulted in improved osseointegration of the triangular titanium implants in the tibiae of the rabbits. The ratio of bone area in histomorphometry (2D analysis) and bone volume (3D analysis) around the implant were significantly increased after stimulation compared to the untreated controls at sacrifice 84 days after implantation. Conclusion: The developed experimental design of an electrical stimulation system, which was directly located in the defect zone of rabbit tibiae, provided feedback regarding the integrity of the stimulation device throughout an experiment and would allow variations in the stimulation parameters in future studies. Within this study, electrical stimulation resulted in enhanced implant osseointegration. However, direct electrical stimulation of bone tissue requires the definition of dose-response curves and optimal duration of treatment, which should be the subject of subsequent studies.

Does cessation of combustible cigarette and heated tobacco product smoking immediately following a fracture benefit fracture healing? In vivo and in vitro validation.

Combustible cigarette and heated tobacco products (HTPs), the two most frequently used tobacco products, negatively affect bone healing. However, whether smoking cessation following fracture benefits bone healing is unclear. Therefore, this study investigated the effect of smoking cessation immediately after surgery on reduced fracture healing induced by smoking. Smoking combustible cigarettes and heated tobacco products generates cigarette smoking extracts (CSE) (extracts from combustible cigarettes [cCSE] and from HTPs [hCSE], respectively). In vivo, CSEs were injected intraperitoneally into rat models for 3 weeks before femoral midshaft osteotomy and fixation. The rats were then divided into CSE continuation and cessation groups postoperatively. Micro-computed tomography (µCT) and biomechanical analyses were performed 6 weeks postoperatively to assess bone union at the fracture site. In vivo study showed µCT assessment also revealed significantly higher cortical bone mineral density (p = 0.013) and content (p = 0.013), and a higher bone union score (p = 0.046) at the fracture site in the cCSE cessation group than in the cCSE continuation group. Biomechanical assessment revealed that elasticity at the fracture site was significantly higher in the cCSE cessation group than in the cCSE continuation group (p = 0.041). These findings provide that smoking cessation, particularly of combustible cigarette, immediately after a fracture accelerates bone fracture healing and increases mechanical strength at the fracture site.

Preparation of Novel Marine Enterococcus faecium MSD8 Exopolysaccharide Ointment and In Vivo Evaluation of Its Impact on Cutaneous Wound Healing in Male Albino Rats.

The current study describes the isolation of exopolysaccharide (EPS) producing lactic acid bacteria (LAB) from marine samples and testing different sugar additives with different proportions for enhanced EPS yield. The isolate MSD8 showed the most potential, yielding 200 mg/L of EPS after being cultivated at 37 °C for 48 h on de Man Rogosa and Sharpe medium (MRS) supplemented with 3% sucrose. The marine isolate MSD8 was identified as Enterococcus faecium with 99.58% probability using 16S rRNA gene sequencing. The obtained sequence was deposited in GenBank and assigned the accession number MW924065. The feature of MSD8-EPS was characterized by estimating the total carbohydrate content by UV-vis to be ~ 71%. The FTIR analysis further indicated the presence of characteristic bands of polysaccharide. The cytotoxicity of the produced MSD8-EPS was assessed using human skin fibroblasts (HSF). The IC50 was determined to be > 100 µg/mL, which signifies that MSD8-EPS is safe for skin application. The produced EPS was used to prepare a novel ointment, which was tested for wound healing ability in male albino rats. The ointment significantly (P ≤ 0.05) shortened the time needed for wound healing, as it successfully healed the wounds by 94.93% on the 7th day and completely (100%) healed the wound by the 12th day. In comparison, the control group was healed by 73.2% and 84.83%, respectively. The data confirm that the prepared ointment can safely be used for pharmaceutical wound care products.

Study of Antidiabetic Properties of Berberis asiatica and Withania somnifera in Streptozotocin-Nicotinamide-Induced Type II Diabetes Mellitus in Wistar Rats.

Background and aim Diabetes is a chronic metabolic disorder characterized by elevated blood glucose levels. Although current antidiabetic drugs are highly effective, they are associated with various adverse drug reactions, including life-threatening hypoglycemia, skin rashes, and gastrointestinal intolerance, in addition to being costly. This animal-based experimental study aims to develop a herbal alternative or adjuvant to current antidiabetic drugs using Berberis asiatica (BA) and Withania somnifera (WS), which could potentially have fewer adverse drug reactions and reduce the required dose of existing antidiabetic medications. Material and methods Seventy-eight adult albino Wistar rats weighing between 150 and 250 g were used for the study. Diabetes mellitus (DM) was induced by intraperitoneal (i.p) injections of streptozotocin (STZ) (65 mg/kg) 15 minutes after nicotinamide (NIC) (110 mg/kg) administration. As the diabetes was confirmed (blood glucose level > 250 mg/dL), rats were divided into 13 different groups mentioned. The standard antidiabetic drugs (metformin [MET] and glimepiride [GLI]) and polyherbal combinations (PHC) (BA + WS) were administered orally, individually (WS and BA), and in combination (BA + WS). Blood samples were collected for biochemical analysis using the tail vein prick method.  The study is based on a total of 13 groups, six rats in each group. Groups 1 and 2 (normal control [NC] and diabetic control [DC]) received distilled water at a dose of 10 mL/kg orally for 28 days. Groups 3-5 (BA 250, 500, and 1000) received dried ethanolic root extract of BA at a dose of 250, 500, and 1000 mg/kg orally, respectively, for 28 days. Groups 6-8 (WS 250, 500, and 1000) received dried ethanolic root extract of WS at a dose of 250, 500, and 1000 mg/kg orally, respectively, for 28 days. Groups 9-11 (PHC 250, 500, and 1000) received dried ethanolic root extract of BA + WS at a dose of 250, 500, and 1000 mg/kg orally, respectively, for 28 days. Groups 12 and 13 (MET and GLI) received standard drugs MET and GLI at a dose of 250 and 10 mg/kg orally, respectively, for 28 days. Results The dried ethanolic root extract of medicinal herbal plants BA and WS and their combination exhibited significant antidiabetic efficacy. PHC has been shown to have a superior antidiabetic effect than individuals. PHC 500 and 1000 showed blood glucose levels similar to those of the GLI group (P < 0.05). Additionally, PHC 1000 showed blood glucose levels similar to those of the MET group (P < 0.05). Conclusion Our results indicate that both BA and WS possess hypoglycemic activity, and their combination also has a synergistic antidiabetic effect compared to the individual extract. These findings are promising in developing new safe and cost-effective herbal combinations as alternatives or additives to currently used synthetic antidiabetic drugs.

Controlled Lateral Pressure on Cortical Bone Using Blade-Equipped Implants: An Experimental Study in Rabbits.

BACKGROUND: This study aimed to evaluate the biological behavior of a novel implant design incorporating decompressive cervical blades. Hence, the aim of the present study was to evaluate the healing outcomes in cortical regions where decompressive protocols were implemented using implants equipped with blades and installed applying a bicortical anchorage. MATERIALS AND METHODS: Blades with varying diameters were integrated into the coronal portion of the implant to prepare the cortical region of rabbit tibiae. The blade diameters differed from the implant collar by the following amounts: control group (0 µm), +50 µm, and +200 µm. RESULTS: No marginal bone loss was detected. Instead, all implants exhibited new bone formation in the coronal region. Complete closure was observed in the CG-0 group, as well as in the TG-50 and TG-200 groups, despite the presence of marginal gaps without primary bone contact at installation. In the apical region, most implants breached the cortical layer. Nevertheless, new bone formation in this region completely closed the osteotomy, effectively isolating the internal environment of the tibia from the external. CONCLUSIONS: The use of a blade incorporated into the implant body enabled precise preparation of the cortical layer, allowing for controlled decompression in the targeted area. This technique resulted in optimal osseointegration with no loss of marginal bone, and complete restoration of marginal gaps ranging from 0 µm to 200 µm.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.