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Purpose: To evaluate a new cultivated coral graft (CCG) in an in vivo experimental guided bone regeneration (GBR) procedure. Materials and Methods: The calvarias of eight 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. All defects were covered with a collagen membrane. Subjects were euthanized after 8 weeks. Results: Histologic 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 = not significant). 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. Conclusions: The existing data supports the complete degradation of CCG as a space-maintaining scaffold for GBR procedures. [ABSTRACT FROM AUTHOR]

Surgical flaps are rudimentary tools in reconstructive surgery, especially following extensive solid tumour resections. They cover skin and soft tissue defects but are prone to ischaemia and necrosis. Since their primary aim is reconstruction, they rarely exhibit a therapeutic activity against the treated disease. Attempts have been made to develop a new therapeutic strategy—biologic brachytherapy, which uses genetically engineered surgical flaps as a drug delivery vehicle, allowing the flap tissue to act as a "biologic pump". This systematic review summarizes the preclinical evidence on using genetically modified surgical flaps. A literature search was conducted in PubMed, EMBASE, Scopus and Web of Science. The initial literature search yielded 714 papers, and, eventually, seventy-seven studies were included in qualitative analysis. The results show that genetic enhancement of flaps has been used as a local or systemic therapy for numerous disease models. Frequently, it has been used to increase flap survival and limit ischaemia or promote flap survival in a non-ischemic context, with some studies focusing on optimizing the technique of such gene therapy. The results show that genetically modified flaps can be successfully used in a variety of contexts, but we need more studies to implement this research into specific clinical scenarios. [ABSTRACT FROM AUTHOR]

ABSTRACT Trypanosomatids are the etiologic agents of numerous parasitic diseases that cause significant morbidity and mortality in millions of people and animals around the world. Approved antitrypanosomatid agents are limited by several drawbacks, such as severe toxicity, lengthy treatment, need for hospitalization, and susceptibility to drug resistance. Consequently, parasitic diseases remain a substantial public health problem, and new drugs are required, especially drugs suitable for rural health systems that have limited resources. In an attempt to find antitrypanosomatid agents to address this problem, we report here on the synthesis and biological efficacy of ferrocene derivatives of nifuroxazide and nitrofurazone, which were designed by replacing the nitrofuran scaffold within their structures with the ferrocene moiety. The 1,2‐disubstituted ferrocene intermediates 8 and 9, featuring amine and carboxaldehyde groups, exhibited the best in vitro antiamastigote activity against Leishmania major strain NIH S and Leishmania donovani strain 9515, respectively. Ferroxazide derivative 15 was revealed as a mammalian cell nontoxic hit compound against Trypanosoma congolense strain IL3000 trypomastigotes; however, no in vivo treatment efficacy was observed against T. congolense strain IL3000‐infected BALB/c mice during a preliminary animal study. The synthesized ferrocene derivatives were poorly soluble in the in vitro and in vivo testing media, hindering uniform sampling and dosing. This study's outcome indicates that replacing the 5‐nitrofuran moiety with ferrocene did not increase antitrypanosomatid activity compared to the nitrofuran parent drugs nifuroxazide and nitrofurazone. [ABSTRACT FROM AUTHOR]

Objectives : This study aimed to analyze the efficacy of stem cell-based tissue engineering for the treatment of alveolar cleft (AC) and cleft palate (CP) defects in animal models. Design : Systematic review and meta-analysis. Setting : Preclinical studies on alveolar cleft repair in maxillofacial practice. Patients, Participants : Electronic search was performed using PubMed, Embase, and Cochrane databases. Pre-clinical studies, where stem cell-based tissue engineering was used in the reconstruction of AC and CP in animal models were included. Quality of the selected articles was evaluated using SYRCLE (SYstematic Review Centre for Laboratory animal Experimentation). Interventions : Review of alveolar cleft bone augmentation interventions in preclinical models. Main Outcome Measures : Outcome parameters registered were new bone formation (NBF) and/or bone mineral density (BMD). Results : Thirteen large and twelve small animal studies on AC (21) and CP (4) reconstructions were included. Studies had an unclear-to-high risk of bias. Bone marrow mesenchymal stem cells were the most widely used cell source. Meta-analyses for AC indicated non-significant benefits in favor of: (1) scaffold + cells over scaffold-only (NBF P =.13); and (2) scaffold + cells over empty control (NBF P =.66; BMD P =.31). Interestingly, dog studies using regenerative grafts showed similar to superior bone formation compared to autografts. Meta analysis for the CP group was not possible. Conclusions : AC and CP reconstructions are enhanced by addition of osteogenic cells to biomaterials. Directions and estimates of treatment effect are useful to predict therapeutic efficacy and guide future clinical trials of bone tissue engineering. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Medicinal plants have been the focus of scientific research for many decades worldwide, especially those used in traditional medicine. Objective: To perform the phytochemical analysis of extracted walnut oil (EWO) and its subchronic toxicity profile in Sprague Dawley rats. Methods: In this experimental study, the collected Kurdish walnut was authenticated by an authorized taxonomist and the core was obtained. Then, the walnut oil was extracted using the cold press method and sent for phytochemical analysis using GC-MS. Accordingly, the male Sprague Dawley rats were treated with varying doses of the EWO for four consecutive weeks, and animals were checked daily for abnormality and toxicity behaviours while they were weighed each week. At the end of the study, animals were sacrificed under deep anaesthesia, blood samples and organs were collected, and various hematological and biochemical tests were performed together with histopathological analysis. Results: GC-MS analysis showed that EWO contained 49 compounds, some critical in biomedical fields. The body weight of all treated animals was increased significantly. No significant changes were seen for hematological tests except platelets, which decreased in all treated groups (p =0.015) compared to the control group. At the same time, AST and chloride levels were decreased (p=0.002 and p=0.012, respectively), while total protein and calcium were increased (p =0.004 and p=0.033, respectively). Simultaneously, histopathological analysis showed no severe lesions in the brain, moderate lesions in the liver and mild, moderate and severe lesions in the kidneys. Conclusions: EWO is rich in various compounds that contain active medicinal components. The EWO can be used at low doses as it does not affect most hematological and biochemical tests and has no significant toxicity in the vital organs of experimental rats. [ABSTRACT FROM AUTHOR]

Objective: Endoscopic injection is one of the simplest minimally invasive methods for the treatment of gastroesophageal diseases. However, the safety of injection material limits its clinical application. We investigated the feasibility, safety and efficacy of endoscopic autogenous fat transplantation (EAFT) in the lower part of esophagus in the treatment of gastroesophageal reflux disease in New Zealand albino rabbits. Methods: Eight New Zealand albino rabbits were used for autogenous fat transplantation. The dynamic pH value of the lower esophagus was monitored before and one week after fat transplantation in two rabbits. The local retention of fat was observed by endoscopy, and the pathological analysis was made at the junction of esophagus and stomach after two weeks of fat transplantation in six albino rabbits. During the experiment, the weight, dietary habit and infection of albino rabbits were monitored. Results: Endoscopic autogenous fat transplantation of the lower esophagus was successfully performed in 8 albino rabbits. The average pH value of the esophagus increased from 5.6 to 7.5 and 7.4 to 7.9, respectively in two rabbits one week after transplantation. The fat barrier of the lower esophagus was remained locally and observed by endoscopy two weeks after transplantation in six rabbits. Pathology showed that the adipocytes survived in the submucosa with neovascularization. No complications of bleeding, perforation and infection occurred. All albino rabbits kept normal dietary habit. No significant changes in weight were observed. Conclusion: Endoscopic autogenous fat transplantation in lower esophagus is considered as a safe and feasible method by preliminary animal experiments, which can provide a new option in the treatment of gastroesophageal reflux disease (GERD) and is worth further study.

ABSTRACT 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. • Moderate alcohol use increased HDL-C and apoA1 levels compared to the control group. • Ethanol group exhibited decreased CRP and trends of decrease in TNF-α and HMGB-1. • 8-oxo-dG, a marker of DNA damage, showed a trend of decrease in the ethanol group. • Upregulation of Sod and a trend of increase in Aldh2 observed in the ethanol group. • Moderate alcohol use improved biomarkers related to CVD and CRC risk. [ABSTRACT FROM AUTHOR]

Background: The Mediterranean area is a diversity center for the genus Dianthus. However, species belonging to this genus, including Dianthus orientalis Adams (DOA), have not been investigated for their medicinal activities. Objectives: To investigate antidiabetic, antihyperlipidemic, antioxidant effects and molecular mechanism of D. orientalis Adams leaf extract (DOAE) in an animal model. Materials and methods: The plant leaves were collected from July to August 2021 from Penjween district, Sulaimaniyah, Iraq and then identified, authenticated, shadow-dried, and extracted using pure methanol. Thirty rats were divided randomly into 5 groups of 6 animals each. Group 1 was control negative (CN) and received distilled water (DW). Group 2 was diabetic control (DC) that received DW, while group 3 was control positive (CP) treated with Glibenclamide (GLB, 0.6 mg/kg body weight). Groups 4 and 5 were diabetic rats who received a low-dose (30 mg/kg) and a high-dose (90 mg/kg) of DOAE orally for 4 weeks. Then, lipid profile, total antioxidant capacity, histopathological examinations, and molecular studies were conducted. Results: DOAE was more effective than GLB in reducing blood glucose, lipid parameters, liver enzymes, and renal function. Micromorphological assay of livers, kidneys, and pancreas revealed significant restoration in diabetic groups treated with DOAE (90 mg/kg) and GLB compared to the DC group. Microribonuclic acid-21 (miR-21) was significantly expressed in DC but markedly lowered in both DOAE groups, while miR-24 and miR-126 were significantly suppressed in DC and expressed in the DOAE-treated groups. Conclusions: DOAE exerted significant antihyperglycemic, anti-dyslipidemic, antioxidant, and hepatorenal protective effects in diabetic rats. [ABSTRACT FROM AUTHOR]

Background: Healing of critical-size defects is a well-known problem that has been challenged in several studies. The aim of the experiment was to evaluate bone formation and osseointegration of implants installed in critical defects of the mandibular body simultaneously grafted with Bio-Oss® or Cerabone®. Material and methods: Defects, 10 mm wide and 3 mm deep, were prepared at both lateral aspects of the mandible in 12 rabbits. One implant was installed in the center of the defect, and bovine xenografts produced either at low (Bio-Oss®; Low-T) or high (Cerabone®; High-T) temperatures were used to fill the defects. A collagen membrane was placed to cover the sites. Healing was evaluated 10 weeks after surgery. Results: In both groups, most sites showed optimal healing with closure of the coronal entrance of the defects. However, residual defects occupied by soft tissues and biomaterial particles were observed, even though generally limited to some regions of the defect. Osseointegration of the implant surface in the region of the defect was poor in both groups. Conclusions: Circumferential marginal critical-size defects around implants filled with bovine xenografts presented regions with a complete healing in both groups. However, the healing was not complete at all regions in most defects; therefore, a complete optimal healing of critical-size marginal defects cannot be predicted. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to apply the break-even point concept to express the dynamics of bone formation and resorption around implants. Methods: Published data on new bone and parent bone densities around implants from one human and three dog studies were selected and used for analysis. The break-even point (BEP) of the bone density (BD) was assessed. The BEP is the point at which, in a graph, the lines representing the formation of new bone and resorption of old bone intersect. BEP is expressed in time (x; days) of occurrence and percentage of bone (y; %) at which the break-even point occurs and illustrates the grade of bone modeling. The sooner the occurrence, the faster the bone formation in relation to the resorption of the old bone. Results: In the marrow and cortical compartments, BEP of bone density occurred after 7.9 days (BD% 24.5%) and >30 days, respectively. Different surfaces presented similar BEP, ranging between 9.7 and 11.2 days (BD% 19.1–22.5%). BEP at implants installed in the human maxilla occurred after 29–30.4 days (BD% 28.3–29.6%). Conclusion: The present study showed that the parameters used to express the break-even point can provide information on the influence of the model used, surface characteristics, and bone quality on bone modeling/remodeling around implants. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the influence on peri-implant soft and hard tissues of one-piece implants with a convergent hyperbolic profile collar placed at different depths with respect to the bone crest. Materials and Methods: Six dogs were included in the experiment. Three months after mandibular tooth extractions, two one-piece implants carrying a 2.8-mm--high convergent hyperbolic profile collar were placed in the alveolar crest with the coronal margin of the rough surface either 0.8 mm (test-1) or 1.8 mm (test-2) deeper with respect to the bone crest (Ct0). Two similar implants were instead placed flush to Ct0 as controls (control-1 and control-2, respectively). Healing screws were connected, and nonsubmerged healing was allowed. After 4 months, block sections were harvested, and histologic slides were prepared in a buccolingual plane. Results: In the histologic analyses, both the buccal crest and coronal level of osseointegration were located more coronally at the test compared to the control implants concerning the implant. However, the buccal bone crest with respect to Ct0 presented a loss of 0.8 ± 0.4 mm at the test-1 and 0.5 ± 0.4 mm at the control-1 implants (P = .028), and a loss of 2.0 ± 1.0 mm and 0.7 ± 0.4 mm at the test-2 and control-2 implants (P = .028), respectively. At the control implants, the collars were exposed above the peri-implant mucosa, while those of the test implants were not. However, the coronal level of the peri-implant mucosa with respect to Ct0 was located more apically at the test compared to the control implants. Conclusion: The placement of implants with a hyperbolic convergent profile collar in the subcrestal position resulted in higher buccal bone resorption and more soft tissue recession compared to the crestal implants with respect to the level of the bone crest at placement. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate whether the placement of endosseous dental implants along with intentionally retained root fragments enhances peri-implant histologic characteristics and outcomes in healthy animal models. Materials and Methods: Two review authors independently performed electronic literature searches across the PubMed/MEDLINE, LILACS, EBSCOhost, and Science Direct databases by using different keywords and Medical Subject Headings terms to identify relevant articles. Only preclinical animal trials evaluating the histology of peri-implant tissues around endosseous dental implants placed along with intentionally retained root fragments were included in the review. The risk of bias assessment was investigated using the Systematic Review Centre for Laboratory animal Experimentation (SYRCLE) tool, and the reporting quality of each trial was evaluated using the Animal Research: Reporting in Vivo Experiments guidelines. Results: Seven preclinical trials including a total of 33 animals and 155 endosseous dental implants were eligible for the analysis. One trial reported the histologic assessment of peri-implant tissues around endosseous dental implants with ankylotic root fragments, whereas the other six studies used nonankylotic root fragments. The effects of the length of retained root fragments on peri-implant tissues were reported in two trials that showed contrasting results. The effects of the width of retained root fragments were assessed in two trials reporting that a remaining thickness < 2 mm and buccal bone thickness > 3 mm favors alveolar bone preservation over a period of 12 weeks. Although the mean quality assessment score for all preclinical trials was moderately high, the summary for the risk of bias presented a high risk. Conclusion: Limited data and short-term preclinical evidence showed optimal peri-implant histologic findings of endosseous dental implants placed along with intentionally retained root fragments. However, further preclinical histologic evaluation with homogenous populations and long-term controlled clinical studies are needed to substantiate its applicability in clinical situations. [ABSTRACT FROM AUTHOR]

The reproducibility crisis across animal studies jeopardizes the credibility of the main findings derived from animal research, even though these findings are critical for informing human studies. To clarify and improve transparency among animal studies, the ARRIVE reporting guidelines were first announced in 2010 and upgraded to version 2.0 in 2020. However, compliance with and awareness of those reporting guidelines has remained suboptimal. Journal editors should encourage the authors to adhere to those guidelines. Authors, editors, referees, and reviewers should be aware of the ARRIVE guideline 2.0 when assessing and evaluating the methodology and findings of animal studies. However, we should also question whether reporting guidelines alone can change a research culture and improve the reproducibility of animal investigations. Reported research may not reflect actual research. Large segments of animal research efforts are wasted because of poor design choices and because of non-publication rather than suboptimal reporting. Better training of the scientific workforce, interventions at improving animal research at the design stage, registration practices, and alignment of the reward system with the publication of rigorous animal research may achieve more than reporting guidelines alone. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Allergic asthma development and pathogenesis are influenced by airway epithelial cells in response to allergens. Heme oxygenase‐1 (HO‐1), an inducible enzyme responsible for the breakdown of heme, has been considered an appealing target for the treatment of chronic inflammatory diseases. Herein, we report that alleviation of allergic airway inflammation by HO‐1‐mediated suppression of pyroptosis in airway epithelial cells (AECs). Using house dust mite (HDM)‐induced asthma models of mice, we found increased gasdermin D (GSDMD) in the airway epithelium. In vivo administration of disulfiram, a specific inhibitor of pore formation by GSDMD, decreased thymic stromal lymphopoietin (TSLP) release, T helper type 2 immune response, alleviated airway inflammation, and reduced airway hyperresponsiveness (AHR). HO‐1 induction by hemin administration reversed these phenotypes. In vitro studies revealed that HO‐1 restrained GSDMD‐mediated pyroptosis and cytokine TSLP release in AECs by binding Nuclear Factor‐Kappa B (NF‐κB) p65 RHD domain and thus controlling NF‐κB‐dependent pyroptosis. These data provide new therapeutic indications for purposing HO‐1 to counteract inflammation, which contributes to allergic inflammation control. [ABSTRACT FROM AUTHOR]

Background: Carvacrol (CAR) is the active component in essential oils (EOs) of many fragrant plants, including oregano and thyme; however, its high toxicity restricts its usage in biomedical fields, and the self-nano-emulsifying drug delivery system (SNEDDS) was suggested to overcome this issue. Objective: To prepare and characterize the CAR-loaded SNEDDS and to assess its toxicity profile towards healthy rats using the in vivo sub-chronic study. Methods: SNEDDS was prepared from olive oil, dimethyl sulfoxide, Tween-80, and distilled water, then CAR-SNEDDS was prepared by adding 0.5% CAR to SNEDDS and both composites were gently agitated for 72 h at room temperature. Later on, both composites were physiochemically characterized for size/charge (Zetasizer), shape (TEM), crystallinity (XRAD), composition (FTIR), and quantitated (UV-Vis). Additionally, the sub-chronic toxicity of both composites at different doses was conducted by orally treating healthy Sprague Dawley for 4 weeks. Then, the treated rats were checked for toxicological symptoms, food/water intake, and behavioral abnormality. In addition, the blood samples were tested for hematologic/biochemical changes, while vital organs (liver and kidney) were assessed for histopathological alterations. Results: The average globule size, zeta potential, and polydispersity index of CAR-SNEDDS were 158.93 ± 22.18 nm, -22.56 ±1.77 mV, 0.553 ±0.31, respectively. All treated animal tissues, serum biochemical profiles, and total hemograms were normal. At 30-90 mg/kg oral doses, CAR-SNEDDS was not toxic and did not cause mortality. Conclusions: CAR-SNEDDS was successfully synthesized and characterized, and the results from sub-chronic oral toxicity studies showed that the CARSNEDDS were non-toxic and safe for biomedical fields. [ABSTRACT FROM AUTHOR]

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.

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.

Aim: To evaluate the in vivo toxicity of the anionic nanoliposome formulation containing [hydrogenated soy phosphatidylcholine (HSPC)] and [1,2-distearoyl-sn-glycero-3- phosphoglycerol (DSPG)]. Methods: The anionic nanoliposome formulation was prepared by the lipid film hydration method. To assess the toxicity of anionic nanoliposomes, male and female albino mice were weakly treated with intravenous injection of the formulation (100 μmol/kg) for four weeks. The toxicity study was performed by the subacute protocol, four weeks after the last injection. To this end, the plasma levels of lipid indexes, urea, creatinine, AST, ALT, ALP, and fasting blood glucose (FBG) were measured. To evaluate histopathological alterations, the tissues of the vital organs including the heart, liver, kidneys, spleen, and brain were studied using hematoxylin & eosin (H&E) staining. Results: The results showed nonsignificant changes in total cholesterol, LDL-C, HDL-C, creatinine, urea, AST, ALP, and ALT in the liposome-treated mice when compared with control mice. However, plasma levels of triglycerides were significantly decreased (by 64.5 ± 15.3 mg/dL, p = 0.001) and (by 58.75 ± 15.3 mg/dL, p = 0.002) in the liposome-treated male and female mice, respectively, when compared with corresponding control mice. The FBG level was significantly increased by154 ± 20 mg/dL, p = 0.001 in the liposome-treated male mice when compared with the control male mice. The PAB level was significantly decreased by 12 ± 4.2 HK, p = 0.03 in the liposome-treated male mice when compared with the control male mice. Histological examination of vital organs indicated no significant differences in tissue damage between the liposome-treated and control mice. Conclusion: The findings of the present study indicated that DSPG-containing nanoliposome formulation exerted no significant adverse effects on the function of vital organs and blood levels of biochemical biomarkers in healthy mice. However, further investigations are needed to find a safe dose of DSPG liposomes concerning the risk of diabetes.

Abstract Objectives To evaluate the histological parameters and bone mechanical properties around implants with low primary stability (PS) in grafted bone substitutes within an oversized osteotomy. Materials and methods An oversized osteotomy penetrating the double cortical bone layers was made on both femora of 24 New Zealand white rabbits. Bilaterally in the femur of all animals, 48 implants were installed, subdivided into four groups, corresponding to four prepared tissue-engineering bone complexes (TEBCs), which were placed between the implant surface and native bone wall: A: tricalcium phosphate β (TCP-β); B: autologous adipose derived-stem cells with TCP-β (ASCs/TCP-β); C: ASCs transfected with the enhanced-GFP gene with TCP-β (EGFP-ASCs/TCP-β); D: ASCs transfected with the BMP-2 gene with TCP-β (BMP2-ASCs/TCP-β). Trichrome fluorescent labeling was conducted. Animals were sacrificed after eight weeks. The trichromatic fluorescent labeling (%TFL), area of new bone (%NB), residual material (%RM), bone-implant contact (%BIC), and the removal torque force (RTF, N/cm) were assessed. Results ASCs were successfully isolated from adipose tissue, and the primary ASCs were induced into osteogenic, chondrogenic, and adipogenic differentiation. The BMP-2 overexpression of ASCs sustained for ten days and greatly enhanced the expression of osteopontin (OPN). At eight weeks post-implantation, increased %NB and RTF were found in all groups. The most significant value of %TFL, %BIC and lowest %RM was detected in group D. Conclusion The low PS implants osseointegrate with considerable new bone in grafted TEBCs within an oversized osteotomy. Applying BMP-2 overexpressing ASCs-based TEBC promoted earlier osseointegration and more solid bone mechanical properties on low PS implants. Bone graft offers a wedging effect for the implant with low PS at placement and promotes osteogenesis on their surface in the healing period.

Abstract Background The overall confidence in the results of systematic reviews including animal models can be heterogeneous. We assessed the methodological quality of systematic reviews including animal models in dentistry as well as the overall confidence in the results of those systematic reviews. Material & methods PubMed, Web of Science and Scopus were searched for systematic reviews including animal studies in dentistry published later than January 2010 until 18th of July 2022. Overall confidence in the results was assessed using a modified version of the A MeaSurement Tool to Assess systematic Reviews (AMSTAR-2) checklist. Checklist items were rated as yes, partial yes, no and not applicable. Linear regression analysis was used to investigate associations between systematic review characteristics and the overall adherence to the AMSTAR-2 checklist. The overall confidence in the results was calculated based on the number of critical and non-critical weaknesses presented in the AMSTAR-2 items and rated as high, moderate, low and critical low. Results Of initially 951 retrieved systematic reviews, 190 were included in the study. The overall confidence in the results was low in 43 (22.6%) and critically low in 133 (70.0%) systematic reviews. While some AMSTAR-2 items were regularly reported (e.g. conflict of interest, selection in duplicate), others were not (e.g. funding: n = 1; 0.5%). Multivariable linear regression analysis showed that the adherence scores of AMSTAR-2 was significantly associated with publication year, journal impact factor (IF), topic, and the use of tools to assess risk of bias (RoB) of the systematic reviews. Conclusion Although the methodological quality of dental systematic reviews of animal models improved over the years, it is still suboptimal. The overall confidence in the results was mostly low or critically low. Systematic reviews, which were published later, published in a journal with a higher IF, focused on non-surgery topics, and used at least one tool to assess RoB correlated with greater adherence to the AMSTAR-2 guidelines.

Surgical flaps are rudimentary tools in reconstructive surgery, especially following extensive solid tumour resections. They cover skin and soft tissue defects but are prone to ischaemia and necrosis. Since their primary aim is reconstruction, they rarely exhibit a therapeutic activity against the treated disease. Attempts have been made to develop a new therapeutic strategy—biologic brachytherapy, which uses genetically engineered surgical flaps as a drug delivery vehicle, allowing the flap tissue to act as a “biologic pump”. This systematic review summarizes the preclinical evidence on using genetically modified surgical flaps. A literature search was conducted in PubMed, EMBASE, Scopus and Web of Science. The initial literature search yielded 714 papers, and, eventually, seventy-seven studies were included in qualitative analysis. The results show that genetic enhancement of flaps has been used as a local or systemic therapy for numerous disease models. Frequently, it has been used to increase flap survival and limit ischaemia or promote flap survival in a non-ischemic context, with some studies focusing on optimizing the technique of such gene therapy. The results show that genetically modified flaps can be successfully used in a variety of contexts, but we need more studies to implement this research into specific clinical scenarios.

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.

Research using animals contributes significantly to many research and development studies, especially in the biomedical field. Within the scope of the study, conducting animal experiments in accordance with scientific principles and ensuring the ethical use and welfare of animals are issues that should be taken into consideration. In this context, the scientific contribution to be achieved by conducting these studies in line with scientific and ethical principles will be directly proportional. In many studies, while investigating the biological significance, it is seen that the effects of many factors are ignored, the answer to the biological question is investigated with simple experimental designs, or the accurate statistical analyses are not chosen. Therefore, in this study, the principles that a researcher planning an animal study should follow within the scope of the research (animal ethics, 3R, and other R rules, determination of sample size, randomization, and blinding) are briefly mentioned. Then, completely randomized design, regression design, split-unit design, hierarchical (nested) design, mixed effects design, and appropriate statistical analyses for these designs, which are thought to be useful in these studies, are discussed. It is thought that this review will be useful as it contains important summative information that will guide all researchers in planning animal studies accurately and quickly. [ABSTRACT FROM AUTHOR]

Background: A variety of etiological factors that lead to peripheral nerve injury include crushing, traction, long fractures in bones, cutting injuries, entrapment neuropathies, infection, inflammation, and tumours of varying degrees. LIPUS has a variety of biological effects on tissues, including speeding up the regeneration of soft tissues, and lowering inflammatory reactions. In LLLT, low-level laser light with a wavelength of 808 nm is employed to trigger a biological reaction. Purpose: The objective of this study was to evaluate the functional recovery of low-level laser therapy (LLLT) and low-intensity pulsed ultrasound (LIPUS) treating the sciatic nerve in rats. Methods: Using simple random sampling method and the inclusion and exclusion criteria, 18 rats in total were chosen. A mechanical crush will be performed for 30 seconds using haemostatic forceps. The study's rats were divided into 3 groups at random: Group A received ultrasound for 21 days; Group B received laser for 21 days; and Group C received no treatment. The toe spread assay was used to assess functional recovery 3 weeks after surgery. Result: All three groups are statistically significant (p<0.005) when analysed using one-way ANOVA during intervention period (7th, 24th, 21st day) but LLLT & UST has shown better improvement in their functional index than the control group. Conclusion: According to the study's findings, LLLT significantly outperforms LIPUS in improving the functional recovery of an experimentally induced rat model. [ABSTRACT FROM AUTHOR]

Introduction: BiosimCovex, a coronavirus nosode was sourced from a clinical sample. Studies are necessary to investigate the acute and subacute oral toxicity of potentised drugs. The acute, subacute repeated dose toxicity and safety testing of the nosode were conducted as per the OECD and New Drug and Clinical Trial (NDCT 19) rules. Material and methods: Animals were randomized as 10 mice and rats (05 males and 05 females of each species) in acute study, 48 rats (24 males and 24 females) in subacute/repeated dose study, and 24 rabbits (12 males/12 females) in repeated dose studies. In acute, subacute, repeated dose toxicity studies, animals were orally dosed with BiosimCovex and observed for toxic symptoms for 14 days. Results: In acute and subacute studies in rats and mice, no mortalities or significant clinical signs were observed. The body weight and body weight gain in rats were normal and decreased in mice in the acute study. The feed consumption was normal for rats and mice. In male rabbits, body weight was decreased, and the weight gain was observed to be normal in other groups. In repeated dose toxicity studies in rats and rabbits, the clinical signs were found to be normal. Histopathology results reveal that BiosimCovex has not produced any major reactive and toxic changes in all the systemic organs when administered by an oral route up to a high dose. Conclusion: No toxicity was documented using acute, subacute, and repeated dose studies using BiosimCovex, a coronavirus nosode. [ABSTRACT FROM AUTHOR]

This paper provides a comprehensive summary of the main toxicological studies conducted on selenium nanoparticles (NPs) using laboratory animals, up until February 28, 2023. A literature search revealed 17 articles describing experimental studies conducted on warm‐blooded animals. Despite some uncertainties, in vivo studies have demonstrated that selenium NPs have an adverse effect on laboratory animals, as evidenced by several indicators of general toxic action. These effects include reductions of body mass, changes in hepatotoxicity indices (increased enzyme activity and accumulation of selenium in the liver), and the possibility of impairment of fatty acid, protein, lipid, and carbohydrate metabolisms. However, no specific toxic action attributable solely to selenium has been identified. The LOAEL and NOAEL values are contradictory. The NOAEL was 0.22 mg/kg body weight per day for males and 0.33 mg/kg body weight per day for females, while the LOAEL was assumed to be a dose of 0.05 mg/kg of nanoselenium. This LOAEL value is much higher for rats than for humans. The relationship between the adverse effects of selenium NPs and exposure dose is controversial and presents a wide typological diversity. Further research is needed to clarify the absorption, metabolism, and long‐term toxicity of selenium NPs, which is critical to improving the risk assessment of these compounds. This review presents the effects of selenium nanoparticles from toxicological in vivo studies demonstrating that a general toxic action in laboratory animals, including reductions of body mass, hepatotoxicity through increase of enzyme activity and accumulation of selenium in the liver, and possible impairment of several metabolic pathways. Proposed NOAEL and LOAEL are also presented and demonstrated controversial results indicating that further research is needed to clarify the toxicity of selenium nanoparticles and improve their risk assessment. [ABSTRACT FROM AUTHOR]

Background: Xenogenous bone has been proposed as an alternative to overcome the disadvantages of autogenous grafting. The aim of the present study was to study bone dynamics at inlay and onlay xenografts used for bone augmentation applying a ring technique. Methods: The bone at the lateral surface of the mandibular angle of 12 adult male New Zealand White rabbits was exposed bilaterally. The cortical layer received multiple perforations on one side of the mandible, and a xenograft block of collagenated cancellous equine bone, 7 mm in diameter and 3 mm in width, was fixed on the prepared surface using an implant (onlay group). On the opposite side, a defect 7 mm in diameter and 3 mm in depth was prepared, and the xenograft block was adapted to the defect and fixed with an implant (inlay group). Results: After ten weeks of healing, in the onlay grafts, new bone was mainly formed on the trabeculae surface, reaching in some specimens the most coronal regions of the block. In the inlay grafts, new bone was found arranged on the trabecular surfaces but also occupying the spaces among the trabeculae. The entrance of the defect was often found close to the top of the block by newly formed bone. A higher percentage of new bone was found in the inlay (19.0 ± 9.3%) compared to the onlay (10.4 ± 7.4%) groups (p = 0.031). The mean gain in osseointegration at the implant in relation to the base of the original 3 mm deep defect was 0.95 ± 1.05% in the onlay group and 0.78 ± 0.71% in the inlay group (p = 0.603). Conclusion: The inlay grafts exhibited a higher new bone percentage than the onlay block grafts possibly due to the defect conformation that presented more sources for bone growth. The trabecular conformation and the composition of the grafts made possible the expression of the osteoconductive properties of the material used. This resulted, in several specimens, in the growth of bone on the graft trabeculae toward the most superior regions in both groups and in the closure of the coronal entrance of the defects in the inlay group. The clinical relevance of this experiment is that the ring technique applied as an inlay method could be suitable for bone augmentation. [ABSTRACT FROM AUTHOR]

Aims The first-generation radiofrequency HotBalloon (RHB) is a size-adjustable single-shot device used in atrial fibrillation. The energy output is determined by its central temperature and not by its balloon surface temperature (BST), thus limiting its efficacy and safety. Therefore, a second-generation RHB was developed to monitor BST and enable BST-controlled ablation. This animal study aims to evaluate the accuracy of a newly developed BST-monitoring system and validate the optimal BST for ablation. Methods and results In Protocol 1, thermocapsules were attached to the superior vena cava (SVC) epicardium. The accuracy of BST monitoring was examined during SVC isolation. In Protocol 2, the efficacy and safety of different BST-controlled ablations were examined. In the acute model, electrophysiological and pathological findings were assessed after energy applications with BST at 51, 54, 57, and 60°C. In the chronic model, the lesion durability and pathological findings were assessed 8 weeks after BST-controlled ablation (57 and 60°C). A significant positive correlation was found between the epicardial temperature and the BST-monitoring value (r = 0.98). In the acute model, all target veins were electrically isolated with BST-controlled ablation at ≥57°C (18/18, 100%). In the chronic model, durable lesions were observed in all veins at 60°C, while 44% of the veins showed reconnection at 57°C. In both pathological analyses, significantly greater lesions were observed at 60°C than at 57°C. There were no significant differences in adverse events between the two groups. Conclusion Balloon surface temperature–controlled ablation at 60°C using the second-generation RHB may be optimal for creating durable lesions without compromising safety. [ABSTRACT FROM AUTHOR]

Acute pancreatitis is an aseptic inflammation caused by pathologically activated pancreatic enzymes and inflammatory mediators produced secondarily by neutrophils and other inflammatory cells and is one of the most difficult diseases to treat. This study aimed to investigate the role of neutrophils in pancreatitis by examining tissue dynamics. We created a model of caerulein-induced pancreatitis in 12-week-old male granulocyte colony-stimulating factor knockout mice (G–CSF–KO) and wild-type littermate control mice (six intraperitoneal injections of caerulein [80 μg/kg body weight] at hourly intervals for 2 days). Mice were sacrificed 0, 3, 6, 12, 24, 36, 48, 72, and 168 h after caerulein administration and examined histologically. The survival rate after one week of caerulein administration was 100 % in the control mice, whereas it was significantly lower (10 %) in the G–CSF–KO mice. Histological examination revealed significant hemorrhage and inflammatory cell migration in the G–CSF–KO mice, indicating prolonged inflammation. Prolonged inflammation was observed in the G–CSF–KO mice. Tissue cleanup by neutrophils during the acute phase of inflammation may influence healing through the chronic phase. [ABSTRACT FROM AUTHOR]

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.

PURPOSE: We aimed to histologically evaluate the influence of bone materials used during guided bone regeneration (GBR) on subsequent peri-implantitis in an experimental ligature-induced peri-implantitis model in beagle dogs. METHODS: Bilateral mandibular premolars (PM2-4) were extracted from six beagle dogs. After 3 months, standardized bone defects (3 mm [mesio-distal width] × 2 mm [bucco-lingual width] × 3 mm [depth]) were created in the experimental group, with simultaneous dental implant placement at the center of the defects. The defects were randomly filled with either autograft (AG) or deproteinized bovine bone mineral (DBBM) and covered with a collagen membrane. In the control group, implant fixtures were placed without creating an intrabony defect. After 3 months, a healing abutment was placed. Four weeks later, a 3-0 silk thread was ligated around the implants to induce peri-implantitis. After 4 weeks, the specimens were dissected and histologically examined. RESULTS: There were no clinical findings of inflammation until silk thread ligation. Four weeks after the onset of peri-implantitis, gingival redness and swelling were seen with mild resorption of the peri-implant bone on dental radiographs. There were no significant differences between the AG, DBBM, and control groups for the following parameters: bone-to-implant contact, distance from the implant shoulder to the base of the bone defect, area of bone defect, and area of new bone. CONCLUSIONS: Within the limitations of this study, it can be concluded that peri-implant tissues after GBR using AG and DBBM underwent the same degree of bone resorption by peri-implantitis as the no defect group.

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.

Purpose: To examine the reaction of mucosa over time to a close contact with biomaterial after sinus elevation performed with deproteinized bovine bone mineral (DBBM) granules of two different sizes. Materials and Methods: Bilateral sinus mucosa elevation was performed in 18 New Zealand rabbits through access on the nasal dorsum. DBBM with granule dimensions of either 1 to 2 mm (large group) or 0.250 to 1.0 mm (small group) were used to randomly fill the subantral hollow spaces. Biopsy specimens of the experimental sites from six animals in each group were obtained 2, 4, and 8 weeks after the surgery. Results: The integrity of the sinus mucosa was clinically evaluated during surgery using a ×2.5 magnifying visual device. The sinus mucosa in contact with the biomaterial granules was found to be thinned compared with the pristine mucosa in all periods examined. Three hundred fifty-two thinned zones were found considering all 36 sinuses treated. Perforations of the sinus mucosa with extrusion of granules toward the sinus were observed, increasing in number over time. In the 8-week healing period, five perforations in three sinuses and eight perforations in four sinuses were found in the large and small groups, respectively. No differences were seen between the large and small groups. The differences between 2 and 8 weeks were statistically significant for the thinned mucosa width in both the large and the small groups and for the number of sinuses and perforations for the small group. Conclusion: Thinning zones and perforations of the sinus mucosa were seen increasing in number over time in regions in contact with graft granules in both the large and small groups. [ABSTRACT FROM AUTHOR]

Introduction: Premature ejaculation is one of the problems which men are facing. This disorder can affect the quality of life and in many cases, the fertility of couples. Recent studies have shown that the dapoxetine mechanism affects the spermatogenesis. However, so far, no study has been conducted on the impact of dapoxetine on sexual hormones and spermatogenesis. Therefore, the present study was performed with aim to examine the effects of dapoxetine on sexual hormones and spermatogenesis. Methods: In this study, 32 male albino desert rats weighing 200 to 250 gr were used. The rats were randomly divided into four groups. The first group received saline solution (1mg/kg) via gavage. Groups 2 to 4 were subjected to intervention with dapoxetine at doses of 1, 2, and 4 ml/kg, respectively, administered through gavage. Pathological changes in the testicular, levels of luteinizing hormones, follicle-stimulating hormone, and testosterone were investigated in this study. Data analysis was done using SPSS software (version 22) and ANOVA, Fisher and post hoc tests. P

Introduction: The weight-loss drugs can induce depression. Orlistat is one of the common weight-loss drugs, but preclinical studies about its effect on mood have not been performed. The aim of this study was evaluating the effect of orlistat alone and following inducing stress on mice depressive behavior. Methods: In this fundamental-applied study, male white mice (27±2 g), in six groups having 7 animals were used. Orlistat was administered orally and imipramine (positive control) was injected intraperitonealy daily, depression was induced by the water avoidance stress (WAS) model during 14 days. The activity was evaluated by the Locomotor Activity Test, depression was assessed by measuring the immobility time during the forced swimming test (FST), food consumption in novelty suppressed feeding test (NSFT), and the sucrose preference test. Results: Orlistat (25 mg/kg) did not change the locomotor activity. Stress increased the duration of immobility in the forced swimming test compared to the stress control group (98±2.2 seconds, P0.05). The difference in the results of latency and food consumption during novelty suppressed feeding test in orlistat group compared to the control group and between orlistat-WAS group compared with the WAS alone group were insignificant. In orlistat-WAS group the sucrose preference increased (69/8 %). Imipramine reduced depressive behavior in mice. Conclusion: Orlistat administration did not induce depressive behavior in animals and it did not augment depression when administered during WAS. Evaluating the effect of chronic orlistat administration on depressive behavior is suggested.

Introduction: Dapoxetine is a novel therapeutic agent employed in treating specific diseases. However, its potential impact on renal excretion processes has yet to be thoroughly investigated, necessitating further exploration in this study. Objectives: This research aimed to assess the effects of dapoxetine on renal function and explore any potential disturbances in kidney excretion processes. Materials and Methods: In this study, 32 male Albino rats weighing between 200-250 g were utilized. The rats were randomly divided into four groups. Group one served as the control and received a normal diet, while groups two to four were administered dapoxetine through gavage at doses of 1 mg/kg, 2 mg/kg, and 4 mg/kg, respectively. The study evaluated blood urea nitrogen (BUN), and serum creatinine levels and examined renal pathological changes in the rats. Results: The results demonstrated a significant increase in average BUN levels in group four compared to other groups (P0.05). Importantly, no indications of apoptosis, necrosis, edema, hydropic degeneration, or glomerular changes were observed in any of the renal cells from the rat groups. Conclusion: Dapoxetine administration led to changes in BUN and creatinine levels; however, it did not adversely affect the renal cells’ pathological outcomes. These results suggest that dapoxetine could be considered for use in the future treatment of certain diseases, considering its minimal impact on renal function. Further investigations and clinical trials are warranted to corroborate these findings and inform medical decision-making.

Asthma is an incurable chronic inflammatory pulmonary hyperresponsiveness. As current medications have many adverse effects, the development of new drugs is required. To define the anti-asthmatic effect of Saururus chinensis, animal and RAW264.7 cell models were used. Histopathological evaluation such as H&E and PAS staining; inflammatory cell analysis, such as cell count using equipment and Diff-Quick staining; serum IgE measurement; and asthma/inflammation-related proteins evaluation via RT-PCR, immunofluorescence, ELISA, immunohistochemistry, and western blotting were conducted. In animal study, S. chinensis prevented asthmatic pulmonary changes, such as epithelial cells hyperplasia, inflammatory cells increment, and mucous hypersecretion; controlled Th2 cell-related cytokines (IL-4 and IL-5) including GATA-3 and blocked inflammation occurrence via NF-κB/COX-2/PGE2 pathway. The anti-inflammatory effects and pathways of S. chinensis were confirmed in a cell-based study. Asthma is caused by both Th1/Th2 imbalance and inflammation and as S. chinensis effectively prevents the occurrence of asthma, it should be considered an anti-asthmatic candidate.

AbstractPurpose Surgical resection of the tendon is an effective treatment for severe contracture. Magnetic Resonance-guided Focused Ultrasound (MRgFUS) is a non-invasive ultrasonic therapy which produces a focal increase in temperature, subsequent tissue ablation and disruption. We evaluated MRgFUS as a clinically translatable treatment modality to non-invasively disrupt in vivo porcine tendons.Material and methods In vivo Achilles tendons (n = 28) from 15–20kg Yorkshire pigs (n = 16) were randomly assigned to 4 treatment groups of 600, 900, 1200 and 1500 J. Pretreatment range of motion (ROM) of the ankle joint was measured with the animal under general anesthesia. Following MRgFUS treatment, success of tendon rupture, ROM increase, temperature, thermal dosage, skin burn, and histology analyses were performed.Results Rupture success was found to be 29%, 86%, 100% and 100% for treatment energies of 600, 900, 1200 and 1500 J respectfully. ROM difference at 90° flexion showed a statistically significant change in ROM between 900 J and 1200 J from 16° to 27°. There was no statistical significance between other groups, but there was an increase in ROM as more energy was delivered in the treatment. For each of the respective treatment groups, the maximal temperatures were 58.4 °C, 63.3 °C, 67.6 °C, and 69.9 °C. The average areas of thermal dose measured were 24.3mm2, 53.2mm2, 77.8mm2 and 91.6mm2. The average areas of skin necrosis were 5.4mm2, 21.8mm2, 37.2mm2, and 91.4mm2. Histologic analysis confirmed tissue ablation and structural collagen fiber disruption.Conclusions This study demonstrated that MRgFUS is able to disrupt porcine tendons in vivo without skin incisions.