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Purpose: To investigate the effects of sinus membrane stabilization (via suturing) and dental implant placement on the endo-sinus bone formation in lateral sinus elevations performed without grafting. Materials and Methods: Maxillary sinus elevation surgery using the lateral approach was performed bilaterally on 30 New Zealand white rabbits. The maxillary sinus areas were divided into control and test groups. In the control group, a titanium screw was placed after sinus membrane elevation; in the test group, the sinus membrane was sutured to the lateral walls, and a titanium screw was placed in the center of the alveolar crest. The subjects were sacrificed at 4 and 8 weeks. Then samples were collected, and a microcomputed tomography (micro-CT) analysis was performed. In addition, the volume of newly formed bone, percentage of osseointegration, sinus volume, residual bone height, and implant protrusion length were measured using micro-CT analysis. Results: The sinus volume, volume of newly formed bone, and percentage of osseointegration in the test group were significantly higher than in the control group at 4 weeks (P = .01, P = .04, P = .02, respectively). While the volume of newly formed bone was 17.1 ± 3.08 mm3 in the control group, it was 26.9 ± 14.26 mm3 in the test group at 4 weeks. The volume of newly formed bone significantly decreased from 26.9 ± 14.26 mm3 to 17 ± 3.66 mm3 at 8 weeks (P = .02). No significant difference in residual bone height was found at 4 and 8 weeks (P = .07). No significant difference in implant protrusion length was found between the control and test groups (P = .18). Protrusion length and new bone formation in the sinus showed a negative relationship (P = .01). Conclusions: Suturing the sinus membrane to the lateral sinus wall is an effective approach for increasing osseointegration, bone volume, and sinus volume in the short term. A slow-absorbing suture material can be used to maintain sinus and bone volumes in the long term. [ABSTRACT FROM AUTHOR]

Despite the various treatments proposed with barrier membranes, one of the main challenges for guided bone regeneration (GBR) is maintaining space for large defects and ensuring an adequate blood supply. The presented feasibility case series aims to introduce an original titanium frame (TF) design, customized for each defect, as a modification of well-known principles and materials for GBR to achieve an enhanced and more predictable horizontal and vertical bone augmentation. Three patients with significant horizontal defects were treated with pre-trimmed TFs to create needed space, and then a 50/50 mixture of autograft and bovine xenograft was placed and covered with a collagen membrane. After 8 months of healing, the sites were reopened, and the titanium screws were removed with the frame. An average of 8.0 ± 1.0 mm of horizontal and 3.0 ± 0.0 mm of vertical bone gain were achieved at the time of reentry and implant placement surgery. Bone core biopsy sample was obtained during the implant placement. Histomorphometric analysis revealed that 42.8% of the sample was new vital bone, 18.8% was residual bone graft particles, and 38.4% was bone marrow-like structures. After 3 to 4 months from implant placement, the implants were restored with provisional crowns and then finalized with zirconia screw-retained crowns. This case series suggests that GBR utilizing TFs with or without collagen membranes can be considered a suitable approach for horizontal and vertical bone augmentation. However, based on only three reported cases, the results should be carefully interpreted. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the effect of interleukin-6 (IL-6) inhibitor (tocilizumab) on bacterial infection-associated bone resorption around implants during osseointegration in rabbits. Materials and Methods: At total of 24 male, 9-monthold New Zealand white rabbits were included, and their two mandibular anterior teeth were extracted. Three months after extraction, 24 one-piece Dentium implants (Ø 2.5 mm, intraosseous length of 12 mm) were inserted in the anterior mandible, and the rabbits were divided into four groups (n = 6 per group). Different treatment methods were used in each group: blank control group (BC); only silk ligation (negative control [NC]); silk ligation and injection with minocycline hydrochloride ointment (positive control [PC]); and silk ligation and injection with tocilizumab at 8 mg/kg via the auricle vein (experimental [EP]). Eight weeks later, the animals were sacrificed, and samples were collected and then analyzed using microcomputed tomography (microCT) scanning, immunohistochemical analysis, and histologic analysis. Results: From the microCT measurement, the ratio of the bone volume to the total volume (BV/TV) in the EP group was 67.00% ± 2.72%, which was higher than that in the other three groups (58.85% ± 2.43% in the BC group, 55.72% ± 2.48% in the PC group, and 36.52% ± 3.02% in the NC group). From immunohistochemical analysis, the expression of IL-6 was found to be higher in the NC group than in the BC, PC, and EP groups, but there was no statistical difference between these three groups. Furthermore, the RANKL (receptor activator of nuclear factor-κB ligand) expression was the lowest in the EP group, followed by the BC group, the PC group, and the NC group, which had the highest expression; there was no difference between the NC and PC groups. Upon histologic analysis, significant new bone was found on the implant surfaces in the EP group, sparse and less new bone could be seen in the BC and PC groups, and the most serious bone resorption occurred in the NC group. Conclusions: Tocilizumab, an inhibitor of IL-6, has a certain effect in preventing bone loss around implants caused by bacterial infection during the osseointegration period. [ABSTRACT FROM AUTHOR]

Purpose: To determine the relationship between bone loss that occurs during the peri-implantitis process and variations in implant stability using resonance frequency analysis (RFA) measurement methods. Materials and Methods: Forty selftapping implants were placed in cow ribs, and study scenarios were established according to the affected implant side and bone loss depth (n = 10 implants per group): Case 1 = bone loss on one side (vestibular); Case 2 = bone loss on two opposite sides (buccal and lingual); Case 3 = bone loss on two adjacent sides (buccal and mesial); and Case 4 = foursided bone loss (circumferential). For each group of 10 implants, first a bone loss of 0 mm was evaluated, then 4-mm defects (simulating 1/3 of bone loss) were created and evaluated, and finally 8-mm defects (simulating 2/3 of bone loss) were created and evaluated. Osteotomy measurements were made with a periodontal probe. For each implant, RFA was measured by the same operator using the Beacon system (Osstell). Results: The initial implant stability quotient (ISQ) values of the 40 implants exceeded 70, reflecting an average of 73 in the buccolingual (VL) and 74.8 in the mesiodistal (MD) directions. ISQ measurements in the 10 implants in which bone dehiscence was performed on the vestibular aspect reflected a decrease in ISQ values as bone loss increased. When generating bone loss in two opposite sides (buccal and lingual), a greater decrease in ISQ values was observed when 2/3 of the implant were affected. The average VL ISQ measurement was less than 70 when at sites with 2/3 of bone loss. Conclusions: When bone loss occurs on only one side of the implant, the ISQ values decrease, but the implant maintains good stability. The same occurs when two opposite sides of the implant are affected, as the unaffected side has the least decrease in ISQ value. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the efficacy of combined therapy of teriparatide and raloxifene on the osseointegration of titanium dental implants in a rabbit model of osteoporotic bone. Materials and Methods: Sixty female rabbits were randomly divided into six groups. The sham ovariectomy group (control) consisted of animals that received no medication. Animals in the ovariectomy group (OVX) underwent ovariectomy and received no medication. The combined group consisted of ovariectomized animals that received combined teriparatide (10 mg/kg) for 12 weeks and raloxifene (10 mg/kg) for 12 weeks. The sequential group (SEQ) consisted of ovariectomized animals that received teriparatide (10 mg/kg) for the first 6 weeks and raloxifene therapy (10 mg/kg) for the following 6 weeks sequentially. The parathormone (PTH) and raloxifene (RAL) groups consisted of ovariectomized animals that received only teriparatide (10 mg/kg) for 12 weeks or raloxifene (10 mg/kg) for 12 weeks, respectively. Dental implants (Bilimplant) were placed in the proximal metaphysis of both tibias in all rabbits. Histomorphometric and microCT studies were performed on the specimens obtained from the right tibia bone. Removal torque (RTQ) and implant stability quotient (ISQ) tests were performed on the specimens obtained from the left tibia bone. The results were compared and evaluated statistically. Results: RTQ analysis revealed a statistically significant difference between the mean values of the combined group (93.01 ± 27.19 Ncm) and the OVX group (49.6 ± 12.5 Ncm) (P = .015). The highest mean T0 (implantation day) value was obtained in the control group (67.1 ± 3.4 Ncm), and the lowest mean value was obtained in the OVX group (61.4 ± 3.8 Ncm). The highest T1 mean (3 months after implantation) was obtained by the combined group (76.6 ± 3.8 Ncm), and the lowest mean was obtained by the OVX group (68.9 ± 6.2 Ncm). Histomorphometric analyses showed that the mean percentage of bone-to-implant contact (BIC%) of the combined group (51.2%) was significantly higher than that of the OVX group (28.6%) (P =.006). In the microCT examinations, it was found that the mean BIC% value of the combined group (41.1%) was significantly higher than that of the OVX group (24.1%) (P < .001). Conclusions: According to the results of the current study, combined therapy of teriparatide and raloxifene improves the BIC and osseointegration of titanium dental implants in osteoporotic bone compared with sequential or independent therapy with these agents. [ABSTRACT FROM AUTHOR]

Purpose: To answer the following focus question: In preclinical in vivo experimental models, do oral implants placed in overdimensioned (OD) sites present greater biomechanical properties and histomorphometric parameters of osseointegration compared to implants placed in standard or undersized implant sockets? Materials and Methods: Online databases were searched for controlled animal studies reporting on OD sites up to February 2023. The relative implant-final drill discrepancy (IDD) was used to categorize the control and test groups according to surgical drilling protocol: (1) control: undersized (IDD > 0.5 mm) or standard (IDD = 0.2 to 0.5 mm); and (2) test OD: stress-free oversized (IDD = 0.0 to -0.1 mm); test GAP: friction-free oversized (IDD = -0.1 mm). Random-effects meta-analyses were performed for the outcomes of insertion and removal torque values (ITV and RTV, respectively), bone-to-implant contact (%BIC), and bone density (%BD) for short- (0 to 2 weeks), intermediate- (3 to 4 weeks), and long-term (= 5 weeks) healing periods. Results: Of the 527 records identified, 13 studies met the eligibility criteria. Histologically, the OD and GAP groups prevented ischemic necrosis and extensive bone resorption at the bone-implant interface in both the marginal cortical layer and the trabeculae. Faster and increased rates of bone formation, characterized by primary osteons and highly vascularized tissue, took place in OD sites between 1 and 5 weeks of healing. Meta-analyses indicated statistically significant benefits in favor of (1) control vs OD for short-term healing in extraoral sites, with pooled estimates (weighted mean difference) of ITV = 25.35 Ncm, %BIC = 2.10%, and %BD = 26.19%; (2) control vs OD for long-term healing in intraoral sites, with %BD = 11.69%; (3) control vs GAP for intermediate-term healing in extraoral sites, with %BD = 3.03%; and (4) control vs GAP for long-term healing in extraoral sites, with RTV = 5.57 Ncm. Conclusions: Oversized surgical preparation of the implant site does not seem to provide any additional benefit compared to standard or undersized sites regarding quantitative parameters of osseointegration. However, it does minimize marginal bone resorption and yields better-quality bone healing, despite the comparable results among different experimental animal models in the late postoperative period. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to evaluate the effectiveness of biomaterials in bone healing of critical bone defects created by piezoelectric surgery in rat calvaria. Method and materials: Histomorphologic analysis was performed to assess bone regeneration and tissue response. Fifty animals were randomized into five groups with one of the following treatments: Control group (n = 10), spontaneous blood clot formation with no bone fill; BO group (Bio-Oss, Geistlich Pharma; n = 10), defects were filled with bovine medullary bone substitute; BF group (Bonefill, Bionnovation; n = 10), defects were filled with bovine cortical bone substitute; hydroxyapatite group (n = 10), defects were filled with hydroxyapatite; calcium sulfate group (n = 10), defects were filled with calcium sulfate. Five animals from each group were euthanized at 30 and 45 days. The histomorphometry calculated the percentage of the new bone formation in the bone defect. Results: All data obtained were evaluated statistically considering P < .05 as statistically significant. The results demonstrated the potential of all biomaterials for enhancing bone regeneration. The findings showed no statistical differences between all the biomaterials at 30 and 45 days including the control group without bone grafting. Conclusion: In conclusion, the tested biomaterials presented an estimated capacity of osteoconduction, statistically nonsignificant between them. In addition, the selection of biomaterial should consider the specific clinical aspect, resorption rates, size of the particle, and desired bone healing responses. It is important to emphasize that in some cases, using no bone filler might provide comparable results with reduced cost and possible complications questioning the very frequent use of ridge presentation procedures. [ABSTRACT FROM AUTHOR]

The biomedical research community addresses reproducibility challenges in animal studies through standardized nomenclature, improved experimental design, transparent reporting, data sharing, and centralized repositories. The ARRIVE guidelines outline documentation standards for laboratory animals in experiments, but genetic information is often incomplete. To remedy this, we propose the Laboratory Animal Genetic Reporting (LAG-R) framework. LAG-R aims to document animals genetic makeup in scientific publications, providing essential details for replication and appropriate model use. While verifying complete genetic compositions may be impractical, better reporting and validation efforts enhance reliability of research. LAG-R standardization will bolster reproducibility, peer review, and overall scientific rigor.

Objectives: This systematic review aimed to search the literature for the answer to the following questions. In human studies: Does the osseodensification technique increase the resonance frequency analysis given in implant stability quotient value and the insertion torque value compared to the conventional technique? In animal studies: Does the osseodensification technique increase implant stability quotient, bone-to-implant contact, and bone area fraction occupancy values over the conventional technique? Data sources: A search forstudies was carried out in eight databases until August 2021. Out of the 447 publications found, 11 were included. Results: In human studies, osseodensification technique showed better results for implant stability quotient values with a summarized median difference of 8.57. As for secondary stability, there was no significant difference, with summarized median difference of 4.49 in favor of the osseodensification technique. In animal studies, all results were favorable to the osseo-densification technique. Regarding insertion torque, bone-to-implant contact, and bone area fraction occupancy between counterclockwise osseodensification technique vs conventional, the mean difference was 46.79 for insertion torque, 2.17 for bone-to-implant contact, and 2.11 for bone area fraction occupancy. High heterogeneity was observed between the studies. The risk of bias in humans was moderate in three studies and low in one; and in animal studies, four presented moderate risk, two low risk, and one high risk. The certainty of evidence ranged from low to moderate. Conclusion: The osseodensification technique showed improvement concerning the resonance frequency and the insertion torque value of implants in human studies. In addition, it increased the values of bone-to-implant contact, bone area fraction occupancy, and implantstability quotient in animal studies, when compared to the conventional technique. [ABSTRACT FROM AUTHOR]

This canine in vivo study assessed the effect of recombinant human platelet-derived growth factor (rhPDGF) on the healing of periapical tissues following apical surgery. From a total of 96 premolar teeth, 64 teeth from six beagle dogs (2 years old) were classified as experimental and were randomly assigned to four experimental groups (16 teeth per group). After having the pulp extirpated, leaving teeth open to the oral cavity for 1 week, and sealing with an immediate restorative material for 8 weeks, nonsurgical endodontic treatment was performed. A split-mouth design was used, and intra-animal randomization of treatment sides was applied to the groups as follows: apical curettage + 1.5-mm root-end resection (Group 1); apicoectomy + mineral trioxide aggregate (MTA) root-end filling (Group 2); apicoectomy + MTA root-end filling + rhPDGF (Group 3); and apical curettage + rhPDGF (Group 4). The animals were sacrificed 24 months after apical surgery, and histologic and µCT analyses were performed for bone volume loss (BVL). Group 1 showed partial resolution of the periapical lesions without signs of tissue regeneration (BVL: 49.09 ± 10.97 mm3). Group 2 had minimal bone regeneration and showed cementum reformation in 9 teeth, with no direct attachment to the MTA (BVL: 35.34 ± 10.97 mm3). Group 3 showed regeneration of all damaged apical tissues without direct contact between the cementum and MTA (BLV: 4.51 ± 1.55 mm3). Group 4 showed regeneration of PDL, bone, and cementum and attachment of functional cementum fibers (BVL: 2.82 ± 2.3 mm3). The difference in BVL was statistically significant only for Groups 1 and 2 (P < .05). rhPDGF may help regenerate apical tissue structures following apical surgery. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the effect of continuous perioperative clopidogrel treatment on the osseointegration of titanium implants. Materials and Methods: A total of 32 New Zealand rabbits were randomly divided between two groups: a clopidogrel group (n = 16) and a control group (n = 16). For 1 week prior to the surgical placement of a titanium implant in their medial femoral condyle, rabbits in the clopidogrel group received 3 mg/kg of clopidogrel daily, and the control group received only the vehicle. This treatment was continued for another 6 weeks postoperatively. At 6 weeks, the rabbits were euthanized and postmortem histologic and histomorphometric evaluation of the implants was performed. Results: The surgical procedures and postoperative period were uneventful and well tolerated by all animals without any surgical wound dehiscence, signs of infection, or other complication. No implant failure was observed in any of the groups. Histomorphometric analysis showed that bone-to-implant contact (BIC) was 48.77% for the clopidogrel group and 34.65% for the control group, with statistically significant difference between them (P < .001). Moreover, clopidogrel group had significantly greater bone tissue density (40.52% vs 28.74%, respectively; P <.001) and mean trabecular thickness (284.7 μm vs 180.7 μm, respectively; P < .001) in proximity to the implant surface than the control group, while the mean trabecular number had no difference between groups (1.56 vs 1.60, respectively; P = .961). Conclusions: The present study showed that continuous clopidogrel treatment does not negatively affect osseointegration, but rather promotes it in terms of BIC and bone density around the titanium implants. Further studies on the effect of the P2Y12 receptor and its antagonists on peri-implant bone homeostasis may provide useful information or applications for long-term success of dental implant therapy. [ABSTRACT FROM AUTHOR]

Purpose: To review experimental peri-implantitis studies using rat models and summarize different peri-implantitis induction techniques and evaluate their effectiveness. Materials and Methods: Electronic searches were conducted by two independent examiners to address the following issues. Meta-analyses explored the marginal bone loss (MBL) of four types of peri-implantitis induction methods in rats. The detailed induction tactics--such as the implant design, implant size, surgical process, time cost, induction methods, and endpoint measurements--were summarized. Results: Of the 18 included studies, 38.9% of the studies placed implants at the maxillary first molar, and 44.4% placed them at the alveolar ridge region anterior to the maxillary first molar. As for the induction method, the numbers of published studies on ligature methods, bacterial inoculation, and bacterial lipopolysaccharide inoculation were equally high among all selected studies. The total implant survival rate at the end was 160 out of 213 implants (75.11%). Eight studies with high pooled heterogeneity (I2 = 98, P < .01) in the meta-analysis reported an overall MBL (µ-CT) of 0.47 mm (95% CI = 0.14 to 0.81). A subgroup analysis estimated an MBL of 0.31 mm (95% CI = 0.12 to 0.50) for bacterial inoculation and 0.66 mm (95% CI = 0.07 to 1.26) for the ligature method. Histopathologic analysis revealed that peri-implantitis in rats was similar to peri-implantitis lesions in humans. Conclusions: Implant placement at the maxillary first molar with bacterial inoculation and the silk ligature method to build peri-implantitis rat models is reliable to use for research on peri-implantitis. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the effect of supraphysiologic administration of testosterone in an early and late model of implant osseointegration in rat tibiae. Materials and Methods: A total of 40 rats were randomly allocated into four groups (n = 10/group), which were divided according to the type of experiment and time of osseointegration: (1) vehicle (14 days), (2) testosterone (14 days), (3) vehicle (42 days), and (4) testosterone (42 days). Testosterone cypionate (7.5 mg/kg) administration started 4 weeks before implant placement, and the injections were performed daily until euthanasia. Machined-surface titanium implants (2.2 mm in diameter and 4 mm high) were placed bilaterally in the tibia of animals 28 days after the first testosterone injection. At days 14 and 42 after implant placement, euthanasia was performed and the tibiae were harvested to perform biomechanical evaluation and histomorphometric analysis of bone-to-implant contact (BIC%) and bone between the threads (BBT%). Results: There was no statistical difference in the removal torque of the implants between the groups treated with the vehicle (control group) or testosterone (P > .05). At 14 days of osseointegration, the BIC% and BBT% did not differ between vehicle or testosterone groups (P > .05), while at 42 days, both the BIC% and BBT% were significantly reduced by testosterone compared to the vehicle group (P < .05). Conclusions: Testosterone cypionate in supraphysiologic dose impaired late-phase osseointegration in rat tibiae. [ABSTRACT FROM AUTHOR]

Osteoporosis is an increasingly prevalent disease. The development of an osteoporosis-like experimental animal model is of great importance for the study of peri-implant osteogenesis in osteoporosis. The present authors aimed to establish a rapid modeling method of osteoporotic rabbits for implant-bone analysis and validate whether the models can affect the implant osseointegration. The present study included 29 female New Zealand rabbits (age: 5 to 6 months). Two rabbits were lost during anesthetization. Of the remaining 27 rabbits, 18 received an ovariectomy, with 9 receiving dexamethasone injections for 8 weeks (OVX+D group) and 9 receiving equivalent-volume saline injections (OVX group). As a control group, the remaining 9 rabbits were sham-operated and received an equivalent volume of normal saline (SHAM group). Then, serum biochemical markers of bone metabolism were detected and densitometric measurements were performed. Implants were then placed in the tibias of each rabbit. Bone samples (including implants) were obtained after 4, 8, and 12 weeks of healing and were subjected to histologic and histomorphometric analyses. The results showed that the OVX+D group experienced a 32% reduction in bone mineral density (BMD) from baseline. The BMD of the OVX+D group was significantly lower than that of the SHAM and OVX groups. Moreover, alkaline phosphatase (ALP) blood concentrations of in the OVX+D group were increased significantly. The osteoporotic rabbits exhibited marked decreases in osseointegration, characterized by slowed bone formation and decreased bone-to-implant contact (BIC). The combination of an ovariectomy and dexamethasone injections could experimentally induce osteoporosis in rabbits in the short term, which can be used as an appropriate animal model to study the osseointegration of implants under osteoporosis. [ABSTRACT FROM AUTHOR]

Over the past two decades, the Khoury plate technique has been widely utilized with much success to facilitate bone augmentation in critically deficient bone areas. Simply, the technique includes harvesting autogenous bone plates and utilizing them with external screw fixation. The rigidity of the bone plates enclosing the bony defect on both the buccal and lingual surfaces allows for tension-free bone remodeling to occur, favoring an ideal bone-forming environment. Following, a 4- to 6-month healing period, a flap is raised, screws may be removed, and implants are placed. With advancements made in tissue engineering, a novel mineral-organic resorbable bone adhesive (MORBA) formulated from underwater biomimetic marine proteins has recently been utilized for immediate bone-to-bone or bone-to-metal fixation. MORBA is a synthetic, injectable, self-setting, and resorbable load-bearing adhesive biomaterial that exhibits over 300 pounds of fixation strength. The unique adhesive properties of MORBA enable it to immediately stabilize dental implants into host bone. The present article describes a novel modification of the Khoury plate technique that utilizes MORBA as a substitute for screws during bone plate fixation. A step-by-step protocol is described that utilizes this novel biomaterial, favoring a more biologic approach to this conventional technique. This novel modification is surgically easier to conduct and is a more biocompatible option that avoids screw fixation and removal. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate the effects of desensitizing MI Varnish (GC America) applied before or after bleaching on the mineral component of enamel and surface topography. The coronal portions of 10 freshly extracted bovine teeth were segmented for a total of 40 specimens. Enamel specimens obtained from each tooth were randomly divided into four groups (n = 10): Group A = no bleaching; Group B = bleaching with 40% hydrogen peroxide (HP); Group C = MI Varnish applied before bleaching; and Group D = MI Varnish applied after bleaching. The calcium (Ca) and phosphorus (P) levels of the specimens in each group were determined by energy dispersive spectroscopy (EDS). Morphologic changes were observed using scanning electron microscopy (SEM). One-way ANOVA and Tukey HSD tests were used for statistical analyses (α = .05). The mean Ca content of Group B was significantly lower than those of Groups A, C, and D (P < .05). The mean Ca content of Group C was significantly lower than that of Group A (P < .05). There was no significant difference in Ca content between the other groups (P > .05). The mean P content of Group A was significantly higher than those of Groups B to D (P < .05). There was no significant difference in P content between Groups B to D (P > .05). Application of MI Varnish before or after in-office bleaching was effective in reducing mineral loss. However, applying MI Varnish after bleaching was more effective. [ABSTRACT FROM AUTHOR]

This study clinically and histologically evaluated the outcome of a porcineapatite xenograft used to elevate the maxillary sinus floor in a severely atrophic ridge. A two-stage crestal window sinus elevation protocol was conducted in 24 patients with crestal bone ≤ 2 mm. Highly porous porcine carbonate apatite moistened with saline solution was placed in the elevated sinus cavity as the sole grafting material. Bone core biopsy samples were taken at 6, 9, and 12 months after sinus augmentation surgery (at implant placement). Treatment outcomes were assessed using microCT (μCT) and histologic analysis. Statistical analysis was performed using nonparametric Kruskal-Wallis test, followed by post-hoc Dunn multiple comparison test. At 6 months after implant placement, all implants achieved good primary stability (insertion torque ≥ 30 Ncm) and successfully osseointegrated. The residual graft amount (mean ± SE) was low (11.91% ± 1.99%) at 6 months and further decreased (6.11% ± 2.64%) by 12 months. On the contrary, the amount of new bone detected was 18.94% ± 4.08% at 6 months and was significantly (P < .05) increased (40.16% ± 5.27%) at 12 months. Histologic assessment revealed osteoclasts actively resorbing the graft as well as osteoblasts actively forming new bone. In the severely atrophic maxilla, the porcine-apatite xenograft promotes new bone formation while being slowly absorbed. Within the limited sample size, the porcine-apatite xenograft seems to be a good graft material for crestal window sinus augmentation. [ABSTRACT FROM AUTHOR]

Purpose: To investigate bone regeneration among three different bone graft materials in a rat calvarum model. Materials and Methods: A total of 24 rats had two 5-mm defects placed per calvarial. Rats were divided into four groups: bovine xenograft (XG), demineralized bone matrix (DBM), mineralized bone graft (MBG), and collagen membrane control (CC). Within each group, samples were collected at two time points: 4 weeks (T4) and 8 weeks (T8). Bone regeneration was assessed by microcomputed tomography (micro-CT) imaging and was analyzed using MATLAB software. Additionally, the fixed samples were subsequently demineralized for immunohistochemistry and histomorphometry. Slides were mounted and stained with hematoxylin and eosin (H&E) stain as well as bone morphogenetic protein 2 (BMP-2) and runt-related transcription factor 2 (RUNX2) markers. The numbers of positive cells/area were calculated for each group and analyzed. Results: At 4 weeks, DBM showed low mineral density (7.7%) compared to the control (25.2%), but increased dramatically at 8 weeks (DBM, T8 = 27.6%; CC, T8 = 27.2%). Xenograft material showed an increase in mineral desnity between T4 and T8 (XG, T4 = 25.0%; XG, T8 = 32.3%). MBG remained consistent over the 8-week trial period (MBG, T4 = 30.4%; MBG, T8 = 30.4%). BMP-2 expression was present in cells adherent to all graft materials. RUNX2 expression was also observed in cells adherent to all graft materials, indicating that during the 4- to 8-week healing period, all materials supported osteogenesis. Conclusions: Compared to other materials, the DBM had high osteoinductive properties during the 4- to 8-week time period based on increased mineral content. All materials were associated with immunohistologic evidence of osteogenesis in the rat calvarial defect model. [ABSTRACT FROM AUTHOR]

Purpose: To use histomorphometric analysis to evaluate bone reconstruction in rabbit calvaria with autogenous bone, anorganic bovine bone, undecalcified human tooth bone (UdTB), and decalcified human tooth bone (dTB) grafts. Materials and Methods: Extracted human teeth were crushed, and tooth bone with and without decalcification was prepared. Bony defects were made in 10 rabbit calvaria and allocated to one of the following four groups: group 1, in which UdTB was grafted; group 2, in which dTB was grafted; group 3, in which anorganic bovine bone was grafted; group 4, in which autogenous bone was grafted. The rabbits were sacrificed at 2 or 8 weeks postoperatively, and histomorphometric comparison was performed. Results: Histologically, new bone formation was observed at the defect margin and around all graft materials. The dTB group revealed significantly greater new bone areas at 2 and 8 weeks compared to the UdTB group and the anorganic bovine bone group (P < .05). The dTB group revealed no significant difference in the new bone area at 2 weeks but revealed significantly less new bone area at 8 weeks compared to the autogenous bone group (P < .05). The dTB group also revealed significantly less graft material area compared to the anorganic bovine bone group at 8 weeks (P < .05). The autogenous bone group revealed significantly less graft material area and significantly greater bone marrow area compared to other groups at 8 weeks (P < .05). Conclusions: Grafting with dTB resulted in better bone regeneration than UdTB and anorganic bovine bone grafting at 8 weeks and addresses the potential disadvantages of autogenous bone grafting. [ABSTRACT FROM AUTHOR]

Purpose: To analyze the process of early oral osseointegration of titanium (Ti) implants in diabetic 129/Sv mice through microCT and histologic and immunohistochemical analysis. Materials and Methods: A group of 30 male 129/Sv mice was equally subdivided into two groups: (1) nondiabetic (ND), in which mice did not undergo systemic alterations and received a standard diet, and (2) diabetic (D), in which mice were provided a high-fat diet from the age of 6 weeks until the conclusion of the study and received two intraperitoneal (IP) injections of streptozotocin (STZ) at a concentration of 100 mg/Kg each. Each mouse underwent extraction of a maxillary first molar, and customized Ti screws (0.50 mm diameter, 1.5 mm length) were placed in the residual alveolar sockets of the palatal roots. At 7 and 21 days after implant placement, the animals were euthanized for maxilla and pancreas collection. Maxillae containing Ti implants were analyzed with microCT, histology, and immunohistochemistry for cells that were positive for F4/80, CD146, runt-related transcription factor 2 (Runx2), and proliferating cell nuclear antigen (PCNA). Pancreata were histologically analyzed. Quantitative data were statistically analyzed with a significance level at 5% (P < .05). Results: ND mice presented successful healing and osseointegration, with a significantly higher fraction of bone volume compared to D mice, both at the alveolar sockets (53.39 ± 5.93 and 46.08 ± 3.18, respectively) and at the implant sites (68.88 ± 7.07 and 44.40 ± 6.98, respectively) 21 days after implant placement. Histologic evaluation revealed that the ND mice showed a significant decrease in inflammatory infiltrate and a significant increase in newly formed bone matrix at 21 days, whereas peri-implant sites in the D mice were predominantly encapsulated by fibrous tissue and chronic inflammatory infiltrate. Immunohistochemical characterization revealed higher Runx2 osteoblast differentiation and higher cell proliferation activity in the ND mice at 7 days, while higher amounts of macrophages were present in D mice at 7 and 21 days. Interestingly, no differences were found in CD146-positive cells when comparing ND and D mice. Conclusions: This study evaluated the effects of immediate dental implant placement in 129/Sv diabetic mice by using specific healing markers to identify changes in cellular events involved in early oral osseointegration. This approach may serve as tool to evaluate new materials and surface coatings to improve osseointegration in diabetic patients. [ABSTRACT FROM AUTHOR]

Objective: To histologically evaluate the effects of a novel human recombinant amelogenin (rAmelX) on periodontal wound healing/regeneration in intrabony defects. Method and mater-ials: Intrabony defects were surgically created in the mandible of three minipigs. Twelve defects were randomly treated with either rAmelX and carrier (test group) or with the carrier only (control group). At 3 months following reconstructive surgery, the animals were euthanized, and the tissues histologically processed. Thereafter, descriptive histology, histometry, and statistical analyses were performed. Results: Postoperative clinical healing was uneventful. At the defect level, no adverse reactions (eg, suppuration, abscess formation, unusual inflammatory reaction) were observed with a good biocompatibility of the tested products. The test group yielded higher values for new cementum formation (4.81 ± 1.17 mm) compared to the control group (4.39 ± 1.71 mm) without reaching statistical significance (P= .937). Moreover, regrowth of new bone was greater in the test compared to the control group (3.51 mm and 2.97 mm, respectively, P = .309). Conclusions: The present results provided for the first-time histologic evidence for periodontal regeneration following the use of rAmelX in intrabony defects, thus pointing to the potential of this novel recombinant amelogenin as a possible alternative to regenerative materials from animal origins. [ABSTRACT FROM AUTHOR]

Purpose: To compare bone substitutes composed of glycated collagen with synthetic micro-sized (1 to 10 µm) hydroxyapatite (OB) vs non-cross-linked collagen matrix with large-particle (250 to 1,000 µm) bovine-derived hydroxyapatite (BOC). Materials and Methods: The P1 to P4 premolars were bilaterally extracted from the mandibles of 19 Beagle dogs. After 21 days, osteotomies were created in each dog that received OB or BOC and were covered with a collagen membrane or were left untreated. The animals were randomly divided into three groups based on sacrifice time (4, 12, or 24 weeks). The right and left hemimandibles were trimmed to facilitate imaging and histology, and all tissues were placed in 10% neutral-buffered formalin. Microcomputed tomography (MicroCT 40 Scanner, Scanco) was used to analyze bone sections. Bone volume, residual material volume, and bone mineral density were determined for each treatment site (OB and BOC) based on a volume of interest that encompassed the original defect. Additionally, blinded histopathologic assessment (based on the ISO 10993-6 scoring system) and histomorphometry were performed on sections ground to < 100 µm thick and stained with Stevenel's blue. Results: No clinical side effects were noted. No statistical differences were observed for OB vs BOC regarding the mineral volume percentage. Compared to OB, BOC had significantly higher mean mineralization densities at 12 weeks (P < .01), but this difference did not extend to 24 weeks. For residual grafting material, bone maturation, alveolar ridge restoration, and inflammatory response, OB showed a residual amount of bone graft and no statistical differences compared to BOC. Conclusion: Both OB and BOC represent valid treatment options for critically sized bone defects. Both bone fillers outperformed the sham-operated, ungrafted (empty) control, demonstrating statistically improved bone growth and ridge restoration. [ABSTRACT FROM AUTHOR]

Objective: To assess the effect of topically applied hyaluronic acid (HA) on the stability of immediately loaded implants in the posterior maxilla. Materials and Methods: For the clinical study, a total of 20 implants were placed in 14 patients seeking the replacement of missing single or multiple posterior maxillary teeth. The patients were randomly divided into two groups. In the clinical control group (CC group), 10 implants were placed and immediately loaded, while in the clinical study group (CS group), 10 implants were coated with HA immediately before placement and immediately loaded. All patients had implant stability clinically evaluated at implant placement time (T0) and 1 (T1), 3 (T3), and 6 (T6) months after loading. Peri-implant pocket depth and modified sulcus bleeding index were evaluated clinically at 6 months in all patients. Bone density was evaluated radiographically after 3 months. All the clinical and radiographic data were subjected to statistical analysis. For the animal study, a total of 12 implants were placed in the tibiae of six rabbits. For each rabbit, 1 implant without any applied HA was placed in the left tibia (AC group), and 1 implant coated with HA was placed in the right tibia (AS group). The rabbits were euthanized at 21 and 45 days after implant insertion. Results: There were no significant statistical differences between the two groups regarding implant stability, peri-implant pocket depth, modified sulcus bleeding index, or bone density from the palatal and apical aspects. However, there was a significant statistical difference in the bone density from the buccal aspect in favor of the study group. The animal study showed that the newly formed bone in the right tibiae showed improved quantity and quality of bone, as it had denser bone trabeculae and smaller marrow spaces compared to the left tibiae. Conclusion: In the clinical study, the application of hyaluronic acid had a superior effect on the buccal bone density around immediately loaded implants. In the animal study, hyaluronic acid had a synergistic effect on the quality and quantity of bone formation around dental implants. [ABSTRACT FROM AUTHOR]

Purpose: To determine the optimal implant diameter under limited bone width by comparing the effects of implants with different diameters on implant stability, peri-implant bone stability, and osseointegration. In addition, to evaluate the reliability of resonance frequency analysis (RFA) in detecting osseointegration and marginal bone level (MBL). Materials and Methods: Mandibular premolars and first molars of seven beagle dogs were extracted. After 8 weeks, their mandibular models and radiographic information were collected to fabricate implant templates. Implant sites were randomly divided into three groups according to diameter: Ø3.3, Ø4.1, and Ø4.8 mm. Implant stability quotient (ISQ) measurement and radiographic evaluation were performed after surgery (baseline) and at 4, 8, and 12 weeks. Three dogs were euthanized at 4 weeks to observe osteogenesis and implant-tissue interface biology. Four dogs were euthanized at 12 weeks to observe osseointegration. Hard tissue sections were prepared to analyze osteogenesis (fluorescence double labeling) and osseointegration (methylene blue-acid fuchsin staining). Results: At baseline and at 4, 8, and 12 weeks, the ISQ values of Ø4.1- and Ø4.8-mm implants did not differ (P > .05), but both had higher values than the Ø3.3-mm implants (P < .05). The mean marginal bone resorption (MBR) associated with Ø3.3-, Ø4.1-, and Ø4.8-mm implants was 0.65 ± 0.58 mm, 0.37 ± 0.28 mm, and 0.73 ± 0.37 mm, respectively. The buccal MBR of Ø4.8-mm implants was significantly higher than that of Ø4.1-mm implants (P < .05). The bone-to-implant contact (BIC) percentage at 12 weeks did not differ for any group (P > .05). The correlation coefficients between the ISQ and MBL of the Ø3.3-, Ø4.1-, and Ø4.8-mm implants were -0.84 (P < .01), -0.90 (P < .001), and -0.93 (P < .001), respectively, while that between the ISQ and BIC was 0.15 (P > .05). Conclusions: During the early healing stage, the performance of Ø4.1- and Ø4.8-mm implants in terms of implant stability was better than that of Ø3.3-mm implants. Implant diameter may not influence BIC percentage. RFA can be used to evaluate implant stability and MBL but is not suitable to assess the degree of osseointegration. [ABSTRACT FROM AUTHOR]

Purpose: To assess the literature comparing histologic levels of osseointegration for titanium vs zirconia dental implants. Materials and Methods: This systematic review was conducted following the PRISMA guidelines and was registered in PROSPERO (CRD42021236781). Electronic and manual searches were carried out through the PubMed/MEDLINE, PubMed Central, and Embase databases with a platform-specific search strategy combining controlled terms (MeSH and Emtree) and text words. The articles were selected by two independent investigators who evaluated the articles based on the criteria for eligibility. Results: A total of 17 articles were included. All were preclinical studies. The populations included dogs (27.55%), minipigs (14.28%), rats (14.28%), and rabbits (43.89%); and the implantation site varied among the mandible (36.82%), maxilla (9.04%), tibia (17.64%), skull (10.70%), and femur (25.80%). A total of 370 titanium (Ti) implants and 537 zirconia (Zr) implants were evaluated. The average osseointegration (% bone-to-implant contact) for Zr was 55.51% (17.6% to 89.09%), and for Ti was 58.50% (23.2% to 87.85%). There was no statistical difference between studies at the 2-month follow-up (P = .672), but this difference was significant at 1 and 3 months (P < .001). Conclusions: Within the limitations of this review, Zr implants had a similar level of osseointegration compared to Ti implants. Nonetheless, because these findings are based on preclinical research, all data must be carefully examined. [ABSTRACT FROM AUTHOR]

Purpose: To study the effect of BMP-2 on the volumetric and histometric changes in peri-implant defect treatments in animal models. Materials and Methods: An electronic search of four databases and a manual search of peer-reviewed journals for relevant articles were performed. Animal studies with data that compared the volumetric and/or histometric outcomes of peri-implant defect treatment with and without the use of BMP-2 were included. Meta-analyses were performed to analyze the weighted mean difference (WMD) and confidence interval (CI) for the recorded variables. Results: After completing the search process, 21 randomized controlled trials were included. The results of the metaanalyses showed that the WMD of bone-to-implant contact (%BIC) with 4 to 8 weeks and 12 to 24 weeks of follow-up was 15.50% (95% CI = 3.28% to 27.72%, P = .01) and 16.17% (95% CI = 11.17% to 21.16%, P < .00001), respectively, favoring the BMP-2 group. The WMD for the percentage of defect fill with 4 to 8 weeks and 12 to 24 weeks of follow-up was 15.88% (95% CI = 3.90% to 27.86%, P = .009) and 10.48% (95% CI = 0.95% to 20.02%, P = .03), respectively, favoring the BMP-2 group. The WMD for the vertical bone gain with 8 to 16 weeks of follow-up was 1.63 mm (95% CI = 0.58 to 2.67 mm, P = .002), also favoring the BMP-2 group. Conclusion: This review demonstrated that the use of BMP-2 in treating periimplant defects showed better clinical and histometric outcomes than defects not treated with BMP-2 in animal models. [ABSTRACT FROM AUTHOR]

This study describes a complex human in vitro model for evaluating anti‐inflammatory drug response in the alveoli that may contribute to the reduction of animal testing in the pre‐clinical stage of drug development. The model is based on the human alveolar epithelial cell line Arlo co‐cultured with macrophages differentiated from the THP‐1 cell line, creating a physiological biological microenvironment. To mimic the three‐dimensional architecture and dynamic expansion and relaxation of the air‐blood‐barrier, they are grown on a stretchable microphysiological lung‐on‐chip. For validating the in vitro model, three different protocols have been developed to demonstrate the clinically established anti‐inflammatory effect of glucocorticoids to reduce certain inflammatory markers after different pro‐inflammatory stimuli: (1) an inflammation caused by bacterial LPS (lipopolysaccharides) to simulate an LPS‐induced acute lung injury measured best with cytokine IL‐6 release; (2) an inflammation caused by LPS at ALI (air‐liquid interface) to investigate aerosolized anti‐inflammatory treatment, measured with chemokine IL‐8 release; and (3) an inflammation with a combination of human inflammatory cytokines TNFα and IFNγ to simulate a critical cytokine storm leading to epithelial barrier disruption, where the eventual weakening or protection of the epithelial barrier can be measured. In all cases, the presence of macrophages appeared to be crucial to mediating inflammatory changes in the alveolar epithelium. LPS induction led to inflammatory changes independently of stretch conditions. Dynamic stretch, emulating breathing‐like mechanics, was essential for in vitro modeling of the clinically relevant outcome of epithelial barrier disruption upon TNFα/IFNγ‐induced inflammation. [ABSTRACT FROM AUTHOR]

Background: Bone loss caused by microgravity exposure presents a serious threat to the health of astronauts, but existing treatment strategies have specific restrictions. This research aimed to investigate whether salidroside (SAL) can mitigate microgravity-induced bone loss and its underlying mechanism. Methods: In this research, we used hindlimb unloading (HLU) and the Rotary Cell Culture System (RCCS) to imitate microgravity in vivo and in vitro. Results: The results showed that salidroside primarily enhances bone density, microstructure, and biomechanical properties by stimulating bone formation and suppressing bone resorption, thereby preserving bone mass in HLU rats. In MC3T3-E1 cells cultured under simulated microgravity in rotary wall vessel bioreactors, the expression of osteogenic genes significantly increased after salidroside administration, indicating that salidroside can promote osteoblast differentiation under microgravity conditions. Furthermore, the Nrf2 inhibitor ML385 diminished the therapeutic impact of salidroside on microgravity-induced bone loss. Overall, this research provides the first evidence that salidroside can mitigate bone loss induced by microgravity exposure through stimulating the Nrf2/HO-1 pathway. Conclusion: These findings indicate that salidroside has great potential for treating space-related bone loss in astronauts and suggest that Nrf2/HO-1 is a viable target for counteracting microgravity-induced bone damage. [ABSTRACT FROM AUTHOR]

Degenerative disc disease is the leading cause of lower back and leg pain, considerably impacting daily life and incurring substantial medical expenses for those affected. The development of annulus fibrosus tissue engineering offers hope for treating this condition. However, the current annulus fibrosus tissue engineering scaffolds fail to accurately mimic the natural biological environment of the annulus fibrosus, resulting in limited secretion of extracellular matrix produced by the seeded cells and poor biomechanical properties of the constructed biomimetic annulus fibrosus tissue. This inability to match the biomechanical performance of the natural annulus fibrosus hinders the successful treatment of annulus fibrosus defects. In this study, we fabricated decellularized annulus fibrosus matrix (DAFM)/chitosan hydrogel-1 (DAFM: Chitosan 6:2) and DAFM/chitosan hydrogel-2 (DAFM: Chitosan 4:4) by varying the ratio of DAFM to chitosan. Rat annulus fibrosus (AF)-derived stem cells were cultured on these hydrogel scaffolds, and the cell morphology, AF-related gene expression, and Interleukin-6 (IL-6) levels were investigated. Additionally, magnetic resonance imaging, Hematoxylin and eosin staining, and Safranine and Fast Green staining were performed to evaluate the repair effect of the DAFM/chitosan hydrogels in vivo. The gene expression results showed that the expression of Collagen type I (Col-I), Collagen type I (Col-II), and aggrecan by annulus fibrosus stem cells (AFSCs) cultured on the DAFM/chitosan-1 hydrogel was higher compared with the DAFM/chitosan-2 hydrogel. Conversely, the expression of metalloproteinase-9 (MMP-9) and IL-6 was lower on the DAFM/chitosan-1 hydrogel compared with the DAFM/chitosan-2 hydrogel. In vivo, both the DAFM/chitosan-1 and DAFM/chitosan-2 hydrogels could partially repair large defects of the annulus fibrosus in rat tail vertebrae. In conclusion, the DAFM/chitosan-1 hydrogel could be regarded as a candidate scaffold material for the repair of annulus fibrosus defects, offering the potential for improved treatment outcomes. [ABSTRACT FROM AUTHOR]

Subarachnoid hemorrhage (SAH) is a severe subtype of hemorrhagic stroke. The molecular mechanisms of its secondary brain damage remain obscure. To investigate the alterations in gene and metabolite levels following SAH, we construct the transcriptome and metabolome profiles of the rat cerebral cortex post-SAH using whole transcriptome sequencing and untargeted metabolomics assays. Transcriptomic analysis indicated that there were 982 differentially expressed genes (DEGs) and 540 differentially expressed metabolites (DEMs) between the sham group and SAH 1d, and 292 DEGs and 254 DEMs between SAH 1d and SAH 7d. Most notably, DEGs were predominantly involved in the activation of immune and inflammatory pathways, particularly the Complement and coagulation cascades, TNF signaling pathway, and NOD-like receptor signaling pathway. Metabolic analysis revealed that the metabolic pathways of Arginine and proline, Arachidonic acid, Folate biosynthesis, Pyrimidine, and Cysteine and methionine were remarkably affected after SAH. Metabolites of the above pathways are closely associated not only with immune inflammation but also with oxidative stress, endothelial cell damage, and blood-brain barrier disruption. This study provides new insights into the underlying pathologic mechanisms of secondary brain injury after SAH and further characterization of these aberrant signals could enable their application as potential therapeutic targets for SAH. [ABSTRACT FROM AUTHOR]

Introduction: Research quality can be improved with reliable and reproducible experimental results when animal experiments are conducted using laboratory animals with guaranteed microbiological and genetic quality through health monitoring. Therefore, health monitoring requires the rapid and accurate diagnosis of infectious diseases in laboratory animals. Methods: This study presents a performance evaluation of a commercially available multiplex real-time PCR (mRT-PCR) assay for the rapid detection of 12 infectious pathogens (Set 1: Sendai virus [SeV, formally murine respirovirus], Mycoplasma spp., Rodentibacter pneumotropicus, and Rodentibacter heylii; Set 2: Helicobacter spp., Murine norovirus [MNV], Murine hepatitis virus [MHV], and Salmonella spp.; Set 3: Staphylococcus aureus, Streptobacillus moniliformis, Corynebacterium kutscheri, and Pseudomonas aeruginosa). To evaluate the efficacy of the mRT-PCR assay, 102 clinical samples encompassing fecal and cecal specimens were analyzed. The resulting data were then compared with the findings from sequence analysis for validation. Results: The assay’s detection limit ranged from 1 to 100 copies per reaction. Specificity testing involving various viruses and bacteria indicated no crossreactivity between strains. Additionally, the assay exhibited good reproducibility, with mean coefficients of variation for inter- and intra assay variation below 3%. The overall positive rate was 52.9% (n  =  54), with the mRT-PCR assay findings matching sequence analysis results (κ  =  1). MHV (n  =  29, 28.4%) was the most prevalent pathogen, followed by Helicobacter spp. (n  =  28, 27.5%), R. heylii (n  =  18, 17.6%), Mycoplasma spp. (n  =  14, 13.7%), MNV (n  =  12, 11.8%), S. aureus (n  =  9, 8.8%), P. aeruginosa (n  =  4, 3.9%), and R. pneumotropicus (n  =  1, 0.9%). Discussion: This assay offers a rapid turnaround time of 100 min, including 30 min for DNA preparation and 70 min for target DNA/RNA amplification. It ensures accuracy, minimizing false positives or negatives, making it a convenient tool for the simultaneous detection of infectious diseases in many samples. Overall, the propose-d assay holds promise for the effective detection of the most important pathogens in laboratory animal health monitoring. [ABSTRACT FROM AUTHOR]

Introduction: Oral lesions are a common clinical symptom arising from various etiologies and disrupt the patient's quality of life. However, no definite treatment is not yet possible, due to the constantly changing environment of the mouth. In recent years, herbal treatments have gained popularity among patients and physicians due to their availability, safety, affordability, and antimicrobial properties. This research aims to investigate the therapeutic effects of a nano-emulsion of Plantago major standardized extract (PMSE) on oral ulcers in a Wistar rat model using histomorphometry and stereological parameters. Materials and Methods: The study involved 72 Wistar rats divided randomly into 24 groups of 3 each: groups A1 to A4 received one dose to 4 doses of 5% PMSE nano emulsion, groups B1 to B4 received one dose to 4 doses of 10% PMSE nano emulsion, and groups C1 to C4 received one dose to 4 doses of 20% PMSE nano emulsion, groups D1 to D4 received one dose to 4 doses of nano-emulsion without PMSE, groups E1 to E4 received one dose to 4 doses of PMSE, and group F served as the control group. An incision measuring 2 mm in diameter was made in the animals' hard palate using a biopsy punch. A swab containing the necessary material was used to administer the medication orally to the wound. Histological samples were collected on days 2, 4, 6, and 8 and sent to the pathology laboratory for examination. Data analysis was performed using SPSS 26 and setting statistical significance at p < 0.05. Results: Group A showed a high rate of complete and normal re-epithelialization of the wound at 66.7%, compared to the other groups. Group D had a re-epithelialization rate of 50%, while groups C, E, and F had rates of 7.41% and group B had 7.16%. In terms of inflammation reduction, 23.88% of group A had no inflammation, a higher percentage compared to the other groups. Group B and D had no inflammation in 3.33% of cases, lower than the other groups. The study evaluated frequency of re-epithelialization and inflammation levels in different groups on days 2, 4, 6, and 8 after four doses of the drug with no significant differences found among the groups. Conclusion: None of the nano emulsions or PMSE enhanced the healing rate of oral ulcers. However, a 5% PMSE nano emulsion displayed an increase in lesion re-epithelialization. Key message: • Design of PMSE nano emulsion on oral wound healing. • Select a superior formulation for PMSE nano-emulsion on oral wound healing. • The composition of 5% PMSE nano emulsion is suggested for healing oral wounds. [ABSTRACT FROM AUTHOR]

Introduction: The study explored the effects of SHOX2 and RASSF1A DNA methylation in lung cancer (LC). Method: Bronchoalveolar lavage fluid (BALF) samples as well as LC and normal adjacent tissues were collected from 72 LC patients and 35 patients with benign pulmonary nodules. Quantitative analysis of SHOX2 and RASSF1A DNA methylation was performed in benign pulmonary nodules and different stages of LC. The diagnostic value of SHOX2 and RASSF1A DNA methylation in LC and benign pulmonary nodules was determined by receiver operating characteristics analysis. Gain/loss-of-function experiments were constructed in LC cells and mouse models of xenograft and pulmonary nodule metastasis. The levels of SHOX2 and transfer-associated genes were tested through quantitative reverse transcription polymerase chain reaction and Western blot. Malignant phenotype of LC cells was assessed by functional experiment. The tumor volume and weight of mice in xenograft models were measured. Pulmonary nodule metastasis was determined through HE staining assay. 5-azacytidine appeared as a positive control drug. Result: SHOX2 DNA methylation or RASSF1A DNA methylation had diagnostic efficiency in pulmonary nodules and early LC, with the two combined having better diagnostic value. SHOX2 expression was upregulated in LC. Similar to 5-azacytidine, SHOX2 knockdown inhibited LC cell viability, migration, and invasion in vitro as well as restrained LC tumorigenesis and pulmonary nodule metastasis in vivo, whereas overexpressed SHOX2 had the opposite effects. Conclusion: The combination of SHOX2 and RASSF1A DNA methylation had a diagnostic value in pulmonary nodules and early LC. SHOX2 positively modulated the tumorigenesis and metastasis of LC by regulating DNA methylation processes. [ABSTRACT FROM AUTHOR]

Objectives Increasing studies demonstrated the importance of C5a and anti-neutrophil cytoplasmic antibody (ANCA)-induced neutrophil activation in the pathogenesis of ANCA-associated vasculitis (AAV). Sphingosine-1-phosphate (S1P) acts as a downstream effector molecule of C5a and enhances neutrophil activation induced by C5a and ANCA. The current study investigated the role of a S1P receptor modulator, FTY720, in experimental autoimmune vasculitis (EAV) and explored the immunometabolism-related mechanisms of FTY720 in modulating ANCA-induced neutrophil activation. Methods The effects of FTY720 in EAV were evaluated by quantifying haematuria, proteinuria, crescent formation, tubulointerstitial injury and pulmonary haemorrhage. RNA sequencing of renal cortex and gene enrichment analysis were performed. The proteins of key identified pathways were analysed in neutrophils isolated from peripheral blood of patients with active AAV and normal controls. We assessed the effects of FTY720 on ANCA-induced neutrophil respiratory burst and neutrophil extracellular traps formation (NETosis). Results FTY720 treatment significantly attenuated renal injury and pulmonary haemorrhage in EAV. RNA sequencing analyses of renal cortex demonstrated enhanced fatty acid oxidation (FAO) and peroxisome proliferator-activated receptor (PPAR) signalling in FTY720-treated rats. Compared with normal controls, patients with active AAV showed decreased FAO in neutrophils. FTY720-treated differentiated HL-60 cells showed increased expression of carnitine palmitoyltransferase 1a (CPT1a) and PPARα. Blocking or knockdown of CPT1a or PPARα in isolated human neutrophils and HL-60 cells reversed the inhibitory effects of FTY720 on ANCA-induced neutrophil respiratory burst and NETosis. Conclusion FTY720 attenuated renal injury in EAV through upregulating FAO via the PPARα–CPT1a pathway in neutrophils, offering potential immunometabolic targets in AAV treatment. [ABSTRACT FROM AUTHOR]

Purpose: Diet-related factors are of great significance in the regulation of hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-gonad (HPG) axes. In this study, we aimed to investigate the effects of chronic exposure to a high fat diet (HFD), fructose or sucralose on the endocrine functions. Methods: Male, Sprague-Dawley rats received a normal chow diet, HFD, 10% fructose or 0.02% sucralose for 10 weeks. Behavioral changes were assessed by open field (OFT) and elevated plus-maze (EPM) tests at week 8. H&E staining was used to observe pathological changes in adrenal cortex, testis and perirenal adipose tissue. Serum hormone concentrations were quantified via enzyme-linked immunosorbent assay (ELISA). The mRNA expression levels of genes along the HPA and HPG axes were determined using real-time PCR. Results: All types of dietary interventions increased body weight and disturbed metabolic homeostasis, with anxiogenic phenotype in behavioral tests and damage to cell morphology of adrenal cortex and testis being observed. Along the HPA axis, significantly increased corticotropin releasing hormone (CRH), adrenocorticotropic hormone (ACTH) and corticosterone (CORT) concentrations were observed in the HFD or 0.02% sucralose group. For HPG axis, gonadotropin-releasing hormone (GnRH) and estradiol (E2) concentrations were significantly increased in all dietary intervention groups, while decreased concentrations of follicle-stimulating hormone (FSH) and testosterone (T) were also detected. Moreover, transcriptional profiles of genes involved in the synthesis of hormones and corresponding hormone receptors were significantly altered. Conclusion: Long-term consumption of HFD, fructose or sucralose manifested deleterious effects on endocrine system and resulted in the dysregulation of HPA and HPG axes. [ABSTRACT FROM AUTHOR]

Purpose: Ulcerative colitis (UC) is a serious health problem with increasing morbidity and prevalence worldwide. The pathogenesis of UC is complex, currently believed to be influenced by genetic factors, dysregulation of the host immune system, imbalance in the intestinal microbiota, and environmental factors. Currently, UC is typically managed using aminosalicylates, immunosuppressants, and biologics as adjunctive therapies, with the risk of relapse and development of drug resistance upon discontinuation. Therefore, further research into the pathogenesis of UC and exploration of potential treatment strategies are necessary to improve the quality of life for affected patients. According to previous studies, Lactobacillus paracasei Jlus66 (Jlus66) reduced inflammation and may help prevent or treat UC. Methods: We used dextran sulfate sodium (DSS) to induce a mouse model of UC to assess the effect of Jlus66 on the progression of colitis. During the experiment, we monitored mouse body weight, food and water consumption, as well as rectal bleeding. Hematoxylin-eosin staining was performed to assess intestinal pathological damage. Protein imprinting and immunohistochemical methods were used to evaluate the protein levels of nuclear factor-kappa B (NF-κB), mitogen-activated protein kinase (MAPK), and tight junction (TJ) proteins in intestinal tissues. Fecal microbiota was analyzed based on partial 16S rRNA gene sequencing. Results: Jlus66 supplementation reduced the degree of colon tissue damage, such as colon shortening, fecal occult blood, colon epithelial damage, and weight loss. Supplementation with Jlus66 reduced DSS-induced upregulation of cytokine levels such as TNF-α, IL-1β, and IL-6 (p < 0.05). The NF-κB pathway and MAPK pathway were inhibited, and the expression of TJ proteins (ZO-1, Occludin, and Claudin-3) was upregulated. 16S rRNA sequencing of mouse cecal contents showed that Jlus66 effectively regulated the structure of the intestinal biota. Conclusion: In conclusion, these data indicate that Jlus66 can alter the intestinal biota and slow the progression of UC, providing new insights into potential therapeutic strategies for UC. [ABSTRACT FROM AUTHOR]

Purpose: Recent advances have led to greater recognition of the role of mitochondrial dysfunction in the pathogenesis of chronic kidney disease (CKD). There has been evidence that CKD is also associated with dysbiosis. Here, we aimed to evaluate whether probiotic supplements can have protective effects against kidney injury via improving mitochondrial function. Methods: An animal model of CKD was induced by feeding C57BL/6 mice a diet containing 0.2% adenine. KBL409, a strain of Lactobacillus acidophilus, was administered via oral gavage at a dose of 1 × 109 CFU daily. To clarify the underlying mechanisms by which probiotics exert protective effects on mitochondria in CKD, primary mouse tubular epithelial cells stimulated with TGF-β and p-cresyl sulfate were administered with butyrate. Results: In CKD mice, PGC-1α and AMPK, key mitochondrial energy metabolism regulators, were down-regulated. In addition, mitochondrial dynamics shifted toward fission, the number of fragmented cristae increased, and mitochondrial mass decreased. These alterations were restored by KBL409 administration. KBL409 supplementation also improved defects in fatty acid oxidation and glycolysis and restored the suppressed enzyme levels involved in TCA cycle. Accordingly, there was a concomitant improvement in mitochondrial respiration and ATP production assessed by mitochondrial function assay. These favorable effects of KBL409 on mitochondria ultimately decreased kidney fibrosis in CKD mice. In vitro analyses with butyrate recapitulated the findings of animal study. Conclusions: This study demonstrates that administration of the probiotic Lactobacillus acidophilus KBL409 protects against kidney injury via improving mitochondrial function. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to investigate the effects of different ω-3 polyunsaturated fatty acid (PUFA) enriched diets, including a novel renewable plant source of ω-3 fatty acids (Buglossoides arvensis), on the development and progression of rheumatoid arthritis (RA). Methods: RA was induced in mice consuming experimental diets using the K/BxN model. The experimental diets consisted of either a western control diet (control), diets containing B. arvensis oil or fish oil. The effects of the diets on platelets, platelet microvesicles (PMVs), and inflammatory markers such as clinical index, ankle thickness and cytokine/chemokine release were measured. Results: While ω-3 PUFA-enriched diets did not prevent the development of arthritis in the K/BxN model, a significant decrease in ankle swelling was observed compared to the control group. Platelets isolated from mice consuming either low content of B. arvensis oil or fish oil diets exhibited significantly decreased PMVs production compared to mice consuming the control diet. Conclusion: Our study provides insight into the contribution of ω-3 PUFA supplementation in modulating the pro-inflammatory phenotype of platelets in RA pathology. Furthermore, our study suggests that low concentrations of dietary B. arvensis oil may have similar anti-inflammatory potential seen with dietary fish oil supplementation. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to investigate the effect of plasma‐activated Ringer's lactate solution (PAL) on oral squamous cell carcinoma (OSCC) cells and carcinogenic processes with a particular focus on iron and collagenous matrix formation. Materials and Methods: We used three OSCC cell lines, one keratinocyte cell line, and two fibroblast lines, and cell viability assays, immunoblotting, flow cytometry, and transmission electron microscopy were performed to evaluate the effect and type of cell death. The effect of PAL treatment on lysyl oxidase (LOX) expression was investigated in vitro and in vivo. Tamoxifen‐inducible Mob1a/b double‐knockout mice were used for the in vivo experiment. Results: PAL killed OSCC cells more effectively than the control nontumorous cells and suppressed cell migration and invasion. Ferroptosis occurred and the protein level of LOX was downregulated in cancer cells in vitro and in vivo. Additionally, PAL improved the survival rate of mice and suppressed collagenous matrix formation. Conclusions: We demonstrated that PAL specifically kills OSCC cells and that ferroptosis occurs in vitro and in vivo. Furthermore, PAL can prevent carcinogenesis and improve the survival rate of oral cancer, especially tongue cancer, by changing collagenous matrix formation via LOX suppression. [ABSTRACT FROM AUTHOR]

Objectives: To explore the effect of protein arginine methyltransferase 5 (PRMT5) on tooth extraction sockets healing, we established an extraction sockets model in osteoblast‐conditional Prmt5 knockout mice. The results provided clues for promoting extraction sockets healing in clinical settings. Materials and Methods: Maxillary first molars were extracted from 6 to 8‐week‐old mice to establish an extraction fossa model. Microcomputed tomography (Micro‐CT), histology, and immunostaining assays were performed on samples harvested at 3‐, 7‐, and 14‐day post‐extraction. Prmt5‐silenced cell lines were employed to explore the regulatory mechanisms underlying the osteigenic differentiation. Results: PRMT5 expression was higher in the early stage of socket healing. Micro‐CT analysis showed that the percentage of new bone in the extraction sockets was lower in OC‐Cre; Prmt5fl/fl mice than in the control group, consistent with Masson staining. We found that, Prmt5 deficiency delayed the osteogenesis during extraction socket healing, which might be achieved through the decrease of H4R3me2s in the Sp7 promoter region. Conclusion: PRMT5 in osteoblasts may promote the differentiation of osteoblasts by regulating the Sp7 promoter H4R3me2s and participate in the healing of tooth extraction sockets. [ABSTRACT FROM AUTHOR]

Objective: The limited understanding of the molecular mechanism for oral submucosal fibrosis (OSF) poses challenges to the development of effective prevention and treatment strategies. The lack of suitable animal models is a major hindrance. Therefore, this study aimed to address this issue by comparing commonly used arecoline‐induced water drinking and injection mouse models. Materials and Methods: The mice were subjected to two protocols: receiving 2 mg/mL arecoline in drinking water and 4 mg/mL arecoline saline solution injections every other day. Tissues were collected at regular 4‐week intervals, with a final time point of 20 weeks. Stereo microscopy and histomorphological analysis were performed on live and harvested tissues, respectively. Results: During arecoline treatment, collagen deposition and myofibroblast proliferation progressively increased in both models. Changes in the collagen I/III ratio indicated that both models exhibited characteristics of the early and intermediate stages of OSF after 20 weeks of arecoline induction. The water‐drinking model also demonstrated multi‐organ fibrosis involving the tongue, lungs, and small intestine. Conclusion: Both the water drinking and injection mouse models effectively induced OSF, but the water‐drinking model better mirrored the observed pathogenesis in patients with OSF. These models provide valuable tools for investigating the mechanisms underlying OSF. [ABSTRACT FROM AUTHOR]

Objective: Lidocaine, a common local anesthetic in medical practice, exhibits anticancer properties across various tumor types. In this study, we aimed to investigate the effects and mechanisms of lidocaine on oral squamous cell carcinoma. Methods: Cell viability and proliferation were assessed through CCK‐8 and EdU assays. Transwell assays were used to analyze cell migration and invasion. Immunofluorescence assays were conducted to determine MMP9 levels. In vivo tumor growth was evaluated using a tumor xenograft model, and Ki67 and MMP9 levels were determined using immunohistochemistry. N6‐methyladenosine levels were assessed using dot plots and ELISA. mRNA and protein levels were examined through reverse transcription‐quantitative PCR or western blot analysis. The association between IGF2BP2 and caveolin‐1 was validated through RIP and luciferase reporter assays. Results: Lidocaine exhibited suppressive effects on the viability, migration, invasion, and tumor formation of oral squamous cell carcinoma. IGF2BP2 expression correlated with poor survival and was downregulated by lidocaine. Lidocaine reduced caveolin‐1 stability by decreasing IGF2BP2 levels. Caveolin‐1 overexpression partially reversed the suppressive effects of lidocaine on the progression of oral squamous cell carcinoma cells. Conclusion: Lidocaine exerts an anticancer role in oral squamous cell carcinoma via IGF2BP2‐mediated regulation of caveolin‐1 stability. [ABSTRACT FROM AUTHOR]

Introduction: Clinical heterogeneity is one of the biggest challenges for researchers studying underlying neurobiological mechanisms in Autism Spectrum Disorder (ASD). We aimed to use polyinosinic-polycytidylic acid [Poly (I:C)] induced maternal immune activation mice model to investigate the behavioral variation and the role of brain circuits related to symptom clusters in ASD. For this purpose, behavioral tests were applied to offsprings and regional thickness was measured from histological brain sections in medial prefrontal cortex, hippocampus and striatum. Methods: Pups of intraperitoneal Poly (I:C)-applied mothers (n: 14) and phosphate buffered saline-applied mothers (n: 6) were used for this study. We used three chamber socialization test and social memory test to evaluate social behavior deficit in mice. Marble burying test was used for assessing stereotypic behavior and new object recognition test for learning and cognitive flexibility. Three subgroups (n: 4 for each) were determined according to behavioral test parameters. Regional thickness was measured in medial prefrontal cortex, hippocampus and striatum and compared between subgroups. Results: We detected that the behavioral differences were distributed in a spectrum as expected in the clinic and also detected increased hippocampus thickness in the stereotypic behavior dominant Poly (I:C) subgroup. Conclusion: Poly (I:C) induced maternal immune activation model creates the behavioral variation and cortical development differences that are seen in relation with symptom groups in ASD. [ABSTRACT FROM AUTHOR]

Objective: The phosphoinositide 3-kinase (PI3K) pathway is an important signaling mechanism for cell proliferation and metabolism. Mutations that activate PIK3CA may make cells p110α dependent, but when phosphatase tensin homolog (PTEN) is lost, the p110β isoform of PI3Ks becomes more important. However, the exact mechanism underlying the prevalence of p110s remains unclear. In this study, our aim was to elucidate the processes behind PI3K isoform dependency in a cellular model of embryonic development. Material and Methods: In order to understand PI3K isoform prevalence, mouse embryonic fibroblasts (MEFs) were used and p110β, PTEN and Rac1 activity was modulated using retroviral plasmids. Expression levels and cellular growth were assessed by performing immunoblots and crystal violet assays. Results: The levels of PTEN had only a partial effect on the prevalence of PI3K isoforms in MEFs. The dependency on p110α diminished when PTEN was depleted. Of note, when PTEN expression was repressed, there was no full transition in dependency from one PI3K isoform to the other. Interestingly, the viability of PTEN-depleted MEFs became less dependent on p110α and more dependent on p110β when p110β was overexpressed. Nevertheless, the overexpression of p110β in conjunction with PTEN knock-downs did not result in a complete shift of isoforms in PI3Ks. Finally, we investigated Rac1 activation with a mutant allele and determined a more potent increase in p110β prominence in MEFs. Conclusion: These findings suggest that multiple cellular parameters, including PTEN status, PI3K isoform levels, and Rac1 activity, combine to influence PI3K isoform prevalence, rather than a single determinant. [ABSTRACT FROM AUTHOR]

The American Medical Association (AMA) was a major player in debates about vivisection in the late 1800s to mid-1950s. This article provides an overview of arguments and guidelines the AMA once offered in favor of the practice in 1909. [ABSTRACT FROM AUTHOR]

If we assume that nonhuman animals experience pain or distress, then ethically justifying human-centered research with only nonhuman animals as subjects likely requires that the research's benefits to humans must, at least, outweigh harms suffered by the nonhuman animals. Yet this reasoning does not seem to account well for the ethical view that nonhuman animals are morally valuable in their own right. This commentary on a case considers this ethical tension and discusses how clinician-researchers should navigate it. This commentary also suggests why clinician-researchers' reasoning about the nature and scope of their obligations to nonhuman animals extends beyond governing regulations and federal oversight, which is silent on or ambiguous about nonhuman animals as morally valuable in their own right. [ABSTRACT FROM AUTHOR]

Objective: Glucocorticoid‐induced tumor necrosis factor receptor superfamily–related protein (GITR), with its ligand (GITRL), plays an important role in CD4+ T cell–mediated autoimmunity. This study aimed to investigate the underlying mechanisms of GITRL in primary Sjögren syndrome (pSS). Methods: Patients with pSS and healthy controls were recruited. Serum GITRL and Th17‐related cytokines were determined. RNA sequencing was performed to decipher key signal pathways. Nonobese diabetes (NOD) mice were adopted as experimental Sjögren models and recombinant adeno‐associated virus (rAAV) transduction was conducted to verify the therapeutic potentials of targeting GITRL in vivo. Results: Serum GITRL was significantly higher in patients with pSS and showed a positive correlation with leukopenia, thrombocytopenia, autoantibodies, lung involvement, and disease activity. Serum GITRL was correlated with Th17‐related cytokines. GITRL promoted the expansion of Th17 and Th17.1 cells. Expansion of granulocyte‐macrophage colony‐stimulating factor positive (GM‐CSF+) CD4+ T cells induced by GITRL could be inhibited by blockade of GITRL. Moreover, GM‐CSF could stimulate GITRL expression on monocytes. RNA sequencing revealed mammalian target of rapamycin complexes 1 (mTORC1) might be the key modulator. The increased phosphorylation of S6 and STAT3 and the expansion of Th17 and Th17.1 cells induced by GITRL were effectively inhibited by rapamycin, suggesting a GITRL–mTORC1–GM‐CSF positive loop in pathogenic Th17 response in pSS. Administration of an rAAV vector expressing short hairpin RNA targeting GITRL alleviated disease progression in NOD mice. Conclusion: Our results identified the pathogenic role of GITRL in exacerbating disease activity and promoting pathogenic Th17 response in pSS through a GITRL–mTORC1–GM‐CSF loop. These findings suggest GITRL might be a promising therapeutic target in the treatment of pSS. [ABSTRACT FROM AUTHOR]

Organoids are small, self-organizing three-dimensional cell cultures that are derived from stem cells or primary organs. These cultures replicate the complexity of an organ, which cannot be achieved by single-cell culture systems. Organoids can be used in testing of new drugs instead of animals. Development and validation of organoids is thus important to reduce the reliance on animals for drug testing. In this review, we have discussed the developmental and regulatory aspects of organoids and highlighted their importance in drug development. We have first summarized different types of culture-based organoid systems such as submerged Matrigel, micro-fluidic 3D cultures, inducible pluripotent stem cells, and air-liquid interface cultures. These systems help us understand the intricate interplay between cells and their surrounding milieu for identifying functions of target receptors, soluble factors, and spatial interactions. Further, we have discussed the advances in humanized severe-combined immunodeficiency mouse models and their applications in the pharmacology of immune-oncology. Since regulatory aspects are important in using organoids for drug development, we have summarized FDA and EMA regulations on organoid research to support pre-clinical studies. Finally, we have included some unique studies highlighting the use of organoids in studying infectious diseases, cancer, and fundamental biology. These studies also exemplify the latest technological advances in organoid development resulting in improved efficiency. Overall, this review comprehensively summarizes the applications of organoids in early drug development during discovery and pre-clinical studies. [ABSTRACT FROM AUTHOR]

Background: Anastomotic leakage (AL) is a dreaded complication following colorectal cancer surgery, impacting patient outcome and leads to increasing healthcare consumption as well as economic burden. Bowel perfusion is a significant modifiable factor for anastomotic healing and thus crucial for reducing AL. Aims: The study aimed to calculate a cut-off value for quantified laser speckle perfusion units (LSPUs) in order to differentiate between ischemic and well-perfused tissue and to assess inter-observer reliability. Methods: LSCI was performed using a porcine ischemic small bowel loop model with the PerfusiX-Imaging® system. An ischemic area, a well-perfused area, and watershed areas, were selected based on the LSCI colormap. Subsequently, local capillary lactate (LCL) levels were measured. A logarithmic curve estimation tested the correlation between LSPU and LCL levels. A cut-off value for LSPU and lactate was calculated, based on anatomically ischemic and well-perfused tissue. Inter-observer variability analysis was performed with 10 observers. Results: Directly after ligation of the mesenteric arteries, differences in LSPU values between ischemic and well-perfused tissue were significant (p < 0.001) and increased significantly throughout all following measurements. LCL levels were significantly different (p < 0.001) at both 60 and 120 min. Logarithmic curve estimation showed an R2 value of 0.56 between LSPU and LCL values. A LSPU cut-off value was determined at 69, with a sensitivity of 0.94 and specificity of 0.87. A LCL cut-off value of 3.8 mmol/L was found, with a sensitivity and specificity of 0.97 and 1.0, respectively. There was no difference in assessment between experienced and unexperienced observers. Cohen's Kappa values were moderate to good (0.52–0.66). Conclusion: Real-time quantification of LSPUs may be a feasible intraoperative method to assess tissue perfusion and a cut-off value could be determined with high sensitivity and specificity. Inter-observer variability was moderate to good, irrespective of prior experience with the technique. [ABSTRACT FROM AUTHOR]