Protective effect of dental pulp stem cells' conditioned medium against cisplatin-induced testicular damage in rats.

Cisplatin is a highly effective chemotherapy drug used to treat most solid tumors. However, one of its side effects is testicular toxicity, which can lead to fertility abnormalities. This study investigated the effectiveness of dental pulp mesenchymal stem cells conditioned medium (DPSC-CM) on cisplatin-induced testicular toxicity. In this study, 36 eight-week-old male Wistar rats were randomly divided into three groups equally (n = 12). Group 1 control "CTR", which received normal saline (0.5 ml) intraperitoneally (i.p), group 2 "Cis" which received an intraperitoneal dose of cisplatin (7 mg/kg), and group 3 "Cis+CM" which received an i.p injection of DPSC-CM (0.5 mg/kg) after cisplatin injection. Biochemical, histomorphometric, and histopathological studies were performed on the testis. Our results exhibited that cis administration led to a decline in total body weight, testis weight, diameter, and volume. A decrease in testosterone and IL-6 serum levels, as well as a decrease in IL-6 and TNFα levels, the activity of catalase and SOD enzymes, and an increase in MDA in testicular tissue were detected. Testicular tissue damage was associated with a significant decrease in tube diameter, germinal epithelium height, number of spermatogonia and Sertoli cells, along with a noticeable increase in basement membrane thickness, and perivascular fibrosis. DMSC-CM improved all the mentioned parameters. Taken together, our results demonstrated that DMSC-CM due to its antioxidant and anti-inflammatory properties, could be effective in reversing cisplatin-induced testicular toxicity.

The effects of vitamin D on cardiovascular damage induced by lipopolysaccharides in rats.

Introduction: Inflammation and oxidative stress are contributed to cardiovascular diseases. Vitamin D (Vit D) has antioxidant and anti-inflammatory properties. In the current research, the effect of Vit D on cardiac fibrosis and inflammation, and oxidative stress indicators in cardiovascular tissues was studied in lipopolysaccharides(LPS) injected rats. Methods: Rats were distributed into 5 groups and were treated for 2 weeks. Control: received vehicle(saline supplemented with tween-80) instead of Vit D and saline instead of LPS, LPS: treated by 1 mg/kg of LPS and was given vehicle instead of Vit D, LPS-Vit D groups: received 3 doses of Vit D (100, 1000, and 10000 IU/kg) of Vit D in addition to LPS. Vit D was dissolved in saline supplemented with tween-80 (final concentration 0.1%) and LPS was dissolved in saline. The white blood cell (WBC) was counted. Oxidative stress markers were determined in serum, aorta, and heart. Cardiac tissue fibrosis was also estimated using Masson's trichrome staining method. Results: WBC and malondialdehyde (MDA) were higher in the LPS group than the control group, whereas the thiol content, superoxide dismutase (SOD), and catalase (CAT) were lower in the LPS group than the control group (P<0.01 and P<0.001). Administration of Vit D decreased WBC (P<0.001) and MDA (P<0.05 and P<0.001) while enhanced thiol (dose 10000 IU/Kg) (P<0.001), SOD (dose 10000 IU/kg) (P<0.001), and CAT (P<0.05 and P<0.001) compared to the LPS group. All doses of Vit D also decreased cardiac fibrosis compared to the LPS group (P<0.001). Conclusion: Vit D protected the cardiovascular against the detrimental effect of LPS. This cardiovascular protection can be attributed to the antioxidant and anti-inflammatory properties of Vit D.

In vitro investigation of canine periodontal ligament-derived mesenchymal stem cells: A possibility of promising tool for periodontal regeneration.

Objectives: Recent investigations indicate that canine periodontal ligament-derived stem cells (cPDLSCs) may reveal a reliable strategy for repair of periodontal tissues via cell-based tissue engineering approaches. Due to limited research, this study aimed to demonstrate the phenotypic characterization of cPDLSc in comparison with canine bone marrow-derived mesenchymal stem cells (cBMSCs) in vitro. Methods: Mesenchymal stem cells (MSCs) were obtained from PDL and BM of five male adult Mongrel dogs. In vitro isolation and expansion as well as biologic characterization including colony unit formation (CFU), osteogenic and adipogenic differentiation, flow cytometric analysis of CD34 and CD44, and RT-PCR of alkaline phosphatase (ALP), osteocalcin (OCN), periostin (POSTN) and S100A4 were performed. Furthermore, electron microscopy analysis was done to complement the comparative research. Results: CFU assay revealed that colonies of cPDLSCs presented 70% confluency with a more finite lifespan than BM-MSCs, showing a significant increase in cPDLSCs. Both types of MSCs showed osteogenic and adipogenic phenotypic characterized with clusters of mineralized depositions and lipid vacuoles, respectively. Both types of MSCs expressed CD44 with limited expression of CD34. RT-PCR of cPDLSCs revealed that expression of ALP, POSTN, OCN and S100A4 genes were significantly higher than those of BMSCs. In addition, comparison of SEM and revealed that cPDLSCs expressed more extracellular collagen fibers. Conclusions: The current study indicated that cPDLSCs show potency as a novel cellular therapy for periodontal regeneration a large animal model.

Using Platelet-Rich Fibrin in Combination With Allograft Bone Particles Can Induce Bone Formation in Maxillary Sinus Augmentation.

BACKGROUND: Sinus pneumatization secondary to posterior maxillary tooth extraction can hinder proper implant installation. Maxillary sinus floor augmentation is a surgical procedure that has been proposed to overcome this issue. PURPOSE: The aim of this study was to evaluate and compare the histomorphometric outcomes of sinus floor elevation using allograft bone particles with or without platelet-rich fibrin (PRF). STUDY DESIGN, SETTING, SAMPLE: This randomized clinical trial included patients scheduled for maxillary sinus floor elevation in the Implant Department of Mashhad Dental School. Healthy adults with an edentulous maxilla and residual alveolar bone height of 3 mm or less were eligible to participate and were randomly allocated to intervention (A) or control (B) groups. Bone biopsies were obtained 6 months postoperatively. PREDICTOR VARIABLE: The predictor variable was using a PRF membrane for maxillary sinus augmentation. In group A, sinus floor elevation was performed using PRF combined with bone allografts, while in group B only allograft particles were used. MAIN OUTCOME VARIABLES: The primary outcome variables were the recorded postoperative histologic parameters, as in the area of newly formed bone, new bone marrow, and residual graft particles (µm2). The secondary outcome variables were the radiographically measured postoperative bone height and width at the graft site. COVARIATES: Age and sex. ANALYSES: Independent sample t-test was employed to compare the postoperative histomorphometric parameters between groups A and B. P value ≤ .05 was considered statistically significant. RESULTS: A total of 20 patients (10 per group) completed the study. The mean rate of new bone formation was 43.25 ± 5.22% in group A and 38.25 ± 7.01% in group B. This difference was statistically insignificant (P = .087). The mean amount of newly formed bone marrow was significantly more in group A compared to group B (6.81 ± 2.19% vs 10.23 ± 4.49%; P = .044). The average amount of remaining particles was also significantly less in group A patients (9.35 ± 3.43% vs 13.18 ± 3.67%; P = .027). CONCLUSION AND RELEVANCE: Incorporating PRF as an adjunctive grafting material results in fewer residual particles of allograft and in more bone marrow formation and may serve as a treatment option for developing the atrophic posterior maxilla.

Effects of Probiotic Lactobacilli plantarum in Treatment of Experimentally Induced Periodontal Disease in Rabbits.

The aim of this study was to evaluate the therapeutic effects of probiotic Lactobacillus plantarum in experimentally induced periodontal disease in rabbits. The incisor teeth of 24 rabbits were scaled under general anesthesia. Two weeks later, silk ligatures were placed at the gingival margin of the incisor teeth to induce periodontal disease. After confirming the presence of periodontal disease by periodontal probing four weeks later, incisor mucogingival flaps were created and gingival pocket lavage and debridement was performed. The rabbits were randomly divided into four groups. Group 1: Control; Group 2: Microencapsulated form of the probiotic; Group 3: Planktonic form of the probiotic; and Group 4: Biofilm form of the probiotic. The rabbits were euthanized eight weeks later, and gingival connective tissue and epithelium were resected for histopathological and histomorphometric evaluation. The results showed that the rate of epithelial regeneration was lower and bone regeneration was significantly higher in the treatment groups compared to the Control group. The highest level of bone regeneration was in Group 2 (Microencapsulated probiotic). There was no significant difference in bone regeneration observed between the biofilm and planktonic probiotic groups. This study showed that applying the probiotic Lactobacillus plantarum in microencapsulated form improved bone regeneration in experimentally induced periodontal disease in rabbits.

Bone Regeneration Effect of Nanochitosan with or without Temporally Controlled Release of Dexamethasone.

INTRODUCTION: Chitosan is a cationic biopolymer, and its modification as a nanoparticle as well as loading a corticosteroid on it may enhance its bone regenerative effect. The aim of this study was to investigate the bone regenerative effect of nanochitosan with or without dexamethasone. METHODS: Under general anesthesia, 4 cavities were created in the calvarium of 18 rabbits and filled with nanochitosan, nanochitosan with a temporally controlled release of dexamethasone (nanochitosan + dexamethasone), an autograft, or left unfilled (control). The defects were then covered with a collagen membrane. The rabbits were randomly divided into 2 groups and were sacrificed at 6 or 12 weeks after surgery. The new bone type, osteogenesis pattern, foreign body reaction, and the type and severity of the inflammatory response were evaluated histologically. The amount of new bone was determined using histomorphometry and cone-beam computed tomographic imaging. One-way analysis of variance with repeated measures was performed to compare results between the groups at each interval. A t test and chi-square test were also conducted to analyze changes in variables between the 2 intervals. RESULTS: Nanochitosan and the combination of nanochitosan and dexamethasone significantly increased the combination of woven and lamellar bone (P = .007). No sample showed a foreign body reaction or any acute or severe inflammation. Chronic inflammation was significantly decreased in number (P = .002) and severity (P = .003) over time. There was no significant difference between the extent and pattern of osteogenesis among the 4 groups, as evaluated by histomorphometry and cone-beam computed tomographic imaging at each interval. CONCLUSION: Nanochitosan and nanochitosan + dexamethasone were comparable with the gold standard of autograft regarding the type and severity of inflammation as well as the level and pattern of osteogenesis; yet, they induced more woven and lamellar bone.

Insights into the protective capacity of human dental pulp stem cells and its secretome in cisplatin-induced nephrotoxicity: effects on oxidative stress and histological changes.

OBJECTIVES: Acute renal injury (AKI) is a major limiting factor for cisplatin administration. Recent evidence suggests the potential contribution of mesenchymal stem cells (MSCs) to rehabilitation from several disorders via both direct and indirect routes. Thus, the present study aimed, for the first time, to explore and compare the reno-protective potential of human dental pulp-derived stem cells (hDPSCs) vs. hDPSC-conditioned medium (hDPSC-CM) in recovery of impaired kidney tissues in a rat animal model of cisplatin-induced AKI. METHODS: AKI was induced via cisplatin injection (n=36). One day after, 24 rats were treated with either hDPSCs or hDPSC-CM (n=12). An extra set of rats (n=12) served as sham group. On days 2 or 7 (n=6), rats were humanly sacrificed for further analysis. Renal injury was explored via measuring serum creatinine and BUN. Renal level of oxidative stress was assessed by determining malondialdehyde, and enzymatic activities of superoxide dismutase and catalase. Renal histopathological changes were scored for comparison among different experimental groups. RESULTS: A single dose of cisplatin resulted in considerable renal dysfunction and oxidative stress. Treatment with hDPSCs or hDPSC-CM resulted in significantly restored renal function, reduced level of oxidative stress, and improved histopathological manifestations. Furthermore, as compared to hDPSC-CM, administration of hDPSCs led to superior results in AKI-induced animals. CONCLUSIONS: The current study described the first comparative evidence of reno-protective potential of hDPSCs and their CM against cisplatin-induced nephrotoxicity in an AKI rat model, proposing them as useful adjunctive therapy in AKI. Yet, future explorations are still needed.

A Comparative Analysis of Photobiomodulation-Mediated Biological Effects of Single Versus Double Irradiation on Dental Pulp Stem Cells: An In Vitro Study.

Objective: In recent years, fractionated irradiation protocols, rather than a simple plan of exposure, have been proposed as a more effective method in the field of tissue regeneration. Thus, this study aimed at a comparative analysis of single versus double irradiation of an 808-nm diode laser, in terms of dental pulp stem cells' (DPSCs) viability and proliferation in vitro. Methods: Subcultured DPSCs were either irradiated, or not (control group), with energy densities of 3, 7, and 12 J·cm-2 in a single- or double-session manner (24 h apart). On 0, 12, 24, 48, and 72 h postirradiation, cell viability and proliferation were evaluated through Trypan Blue and alamarBlue assays, respectively. Results: During the first 48 h postirradiation, the highest rates of DPSC proliferation were assigned to double irradiation at 3 or single exposure to 7 J⋅cm-2, with no cytotoxic effects on cell viability. Inversely, single irradiation at 12, or a double session of exposure to 7 or 12 J⋅cm-2, led to a significant descent in the rates of proliferation and cell viability. Conclusions: Within the limitations of this study, evidence suggests a positive impact on the biological responses of DPSCs following double session of exposure to lower energy densities as well as a single irradiation at a higher energy dosage.

Histological Evaluation of Bone Regeneration Using Hydroxyapatite Based Bone Substitute Derived from Antler: An Animal Study.

OBJECTIVE: Guided bone regeneration (GBR) is considered as a prerequisite in some cases of implant dentistry. For this purpose, bone materials are commonly used. Calcium compounds and Ca-P based materials like hydroxyapatite (HA, Ca10 (PO4)6(OH)2), due to their similarity with the human bone, can be used as graft materials for bone regeneration. This study aimed to evaluate biocompatibility of antler xenograft and compare the osteoconduction effects of antler xenograft with Cerabone in regeneration of calvarium bony defects of rabbits. METHODS AND MATERIALS: Five defects with a diameter of 6 mm and a depth of 3 mm were prepared in the calvarium of four rabbits. Thereafter, two defects were randomly grafted with antler xenograft, two defects were filled with Cerabone, and one defect remained as the untreated group. Histological evaluations, including measuring percentage of new regenerated bone and the amounts of osteoblast, osteoclast, and osteocyte cells, were also performed. To do statistical analyses, paired t-test, chi-square, and Fisher tests were applied. RESULTS: The percentage of new bone formation was significantly higher in antler xenograft (73.33%) and in Cerabone (48.91%) compared to the untreated group (18.91%). The amounts of osteocytes and osteoblasts were obtained as 3.52 ± 0.17 and 2.41 ± 0.24 in the Antler xenograft and as 2.57 ± 0.29 and 2.31 ± 0.32 in the Cerabone group, respectively. Bone marrow formation were significantly higher in antler xenograft (6.66 ± 5.34) and Cerabone (1.99 ± 3.17) compared to the untreated group. CONCLUSION: According to this pilot study, results of using antler xenograft as an osteoconductive materials in regeneration of rabbit calvarial defects are comparable with Cerabone. Although more clinical studies are needed.

Sex steroids-induced neurogenesis in adult brain: a better look at mechanisms and mediators.

Adult neurogenesis is the production of new nerve cells in the adult brain. Neurogenesis is a clear example of the neuroplasticity phenomenon which can be observed in most of mammalian species, including human beings. This phenomenon occurs, at least, in two regions of the brain: the subgranular zone of the dentate gyrus in hippocampus and the ventricular zone of lateral ventricles. Numerous studies have investigated the relationship between sex steroid hormones and neurogenesis of adult brain; of which, mostly concentrated on the role of estradiol. It has been shown that estrogen plays a significant role in this process through both classic and non-classic mechanisms, including a variety of different growth factors. Therefore, the objective of this review is to investigate the role of female sex steroids with an emphasis on estradiol and also its potential implications for regulating the neurogenesis in the adult brain.

Effects of diode low-level laser therapy on healing of tooth extraction sockets: a histopathological study in diabetic rats.

Diabetes mellitus is mostly interrelated to deficiency in wound healing. Low-level laser therapy has been shown to exert reliable effects on the acceleration of wound healing process. This study aimed to determine the potential influence of low-level laser therapy (LLLT) on the healing of extraction sockets in diabetic rats. A total of 24 healthy male Wistar rats were selected for this study. After diabetes induction, the maxillary first molars of all rats were extracted bilaterally. Then, the animals were subjected either to Ga-Al-As laser at 808 nm or to Al-Ga-In-P laser at 660 nm at the right extracted socket every day for the next 14 days. The left sockets served as controls. Rats were sacrificed on the 3rd, 5th, 7th, and 14th days after tooth extraction. The samples were examined by a pathologist. LLLT at 808 nm was able to significantly repress inflammation, improve osteoid formation, and promote vascularization in comparison to the non-treated sockets. LLLT at 660 nm significantly suppressed inflammation and developed vascularization in comparison to the non-treated sockets, but failed to improve osteoid formation in the treated sockets. This study suggests that LLLT could be considered as a reliable treatment for wound healing in diabetic experimental rats.

Protective impact of Rosa damascena against neural damage in a rat model of pentylenetetrazole (PTZ)-induced seizure.

OBJECTIVE: Based on the previously-declared anticonvulsant properties of Rosa damascena (R. damascena), this study explored the probable effects of R. damascena on neuronal apoptosis in the hippocampus of a rat model of pentylenetetrazole (PTZ)-induced seizure. MATERIALS AND METHODS: 40 male Wistar rats were randomely divided into control (n=8) and experimental (n=32) groups which underwent PTZ injection. A one-week pre-medication with 50 (PTZ-Ext 50) (n=8), 100 (PTZ-Ext 100) (n=8), and 200 (PTZ-Ext 200) (n=8) mg/kg of hydro-alcoholic extract of R . Damascene was performed while one experimental group (PTZ-induced group) (n=8) received only saline during the week before PTZ injection. After provocation of PTZ-induced seizures, the brains underwent tissue processing and TUNEL staining assay for apoptotic cell quantification. RESULTS: Our findings revealed that PTZ-induced seizures led to apoptosis in neuronal cells of all sub-regions of the hippocampus; yet, only at CA1, CA3 and DG sub-regions of the PTZ-induced group, the difference in the number of apoptotic neuronal cells was significant in comparison with the control group. In addition, pre-medication with the plant extract led to a significant drop in the quantity of apoptotic neurons in these sub-regions in comparison with the PTZ-induced group which received no pre-medication . CONCLUSION: The results of this study showed that R. damascena extract exerts neuro-protective effects on PTZ-induced seizure.