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In order to acquire the best method that can simultaneously maximize tissue morphology and staining quality, we compared the effect of different fixative and decalcifying solutions on the quality of rabbit and rat bone histology.Fifty-four rat hemimaxillae and 54 rabbit quarter-parietal bones were allocated into 3 fixation groups (formalin, 10 %sodium-phosphate-buffered-formalin and 10 %calcium-phosphate-buffered-formalin). Each fixative was divided into 6 groups and decalcified with 5 % and 10 % nitric acid (NA), 5 % and 10 % formic acid (FA), Gooding-Stewart liquid (GSL) and EDTA. Slide quality was evaluated on hematoxylin/eosin slides by 3 observers and mean-scores for total-cell-characteristics (TCC) and total-tissue-characteristics (TTC) were statistically analyzed.Significant differences in decalcification-time were observed in different combinations of decalcifiers and fixatives in both animals. In rats, TCC was better preserved when using 10 %NA/calcium-phosphate-buffered-formalin compared to 10 %NA/sodium-phosphate-buffered-formalin (P = 0.03). GSL/sodium-phosphate-buffered-formalin performed better than both other fixatives (P 0.001). TCC differed among the decalcifiers in each of the fixatives. In rabbits, there were differences in TCC among the decalcifiers when formalin (P = 0.001) and sodium-phosphate-buffered-formalin (P = 0.01) were used. TTC only showed significant difference when 10 %FA was used in rats (P = 0.044), with formalin performing better than sodium-phosphate-buffered-formalin (P = 0.01).Based on our results, if time is an issue, 10 %NA/calcium-phosphate-buffered-formalin could provide good cellular quality and if time is not a consideration, FA (5 % or 10 %) with sodium-phosphate-buffered-formalin followed by EDTA with formalin, would have the best performance. In rabbits, GSL provides the fastest results, regardless of the fixative and FA/sodium-phosphate-buffered-formalin gives the best cellular quality.

Allergic rhinitis (AR), a major chronic inflammatory disease of the respiratory system, is a public health issue because of its substantial negative impact on quality of life and work efficiency alongside its high prevalence and costs. Dapsone is a sulfone chemical with reported anti-inflammatory and antibacterial properties. Accordingly, we investigated the anti-inflammatory impact of dapsone on ovalbumin-induced allergic rhinitis in balb/c mice.Intraperitoneal ovalbumin and hydroxide aluminum injection followed by intranasal ovalbumin administration sensitized female Balb/c mice. Mice received intraperitoneal dapsone either acute (5, 10, 20 mg/kg) 30 min before the last ovalbumin challenge, or chronic (20 mg/kg) on days 21 to 35.Both acute and chronic intraperitoneal usage of dapsone showed a considerable decrease in the nasal scratching behavior, the number of sneezing, serum IL-4 and IgE levels of ovalbumin-induced AR in balb/c mice, but there was a significant increase in serum IFNγ level. Histopathological analysis demonstrated a significant reduction of eosinophil numbers, following dapsone injection. Goblet cell hyperplasia and respiratory epithelial-thickness decreased significantly in the acute and chronic 20 mg/kg dapsone groups compared to the ovalbumin-induced controls.This study shows that there is an association between acute and chronic dapsone treatment and some anti-allergic effects through an inflammation cascade.

Aim: To evaluate the antimicrobial effects of photoexcited silver sulfadiazine nanoliposomes (AgSD-NLs) doped by curcumin (AgSD-NLs@Cur) on Acinetobacter baumannii. Materials & methods: Following characterization, the cytotoxic and hemolytic activities of AgSD-NLs@Cur were evaluated. The antimicrobial activities of AgSD-NLs@Cur-mediated antimicrobial photodynamic therapy (aPDT) were determined. Histopathological examination of the burn wound sites of infected mice treated with photoexcited AgSD-NLs@Cur was assessed. Results: No significant cytotoxic and hemolytic activities were observed. There was a decrease in the Acinetobacter baumannii count in planktonic and biofilm forms and the gene expression level using AgSD-NLs@Cur-aPDT (p < 0.05). Histopathological analysis indicated the epidermis developed markedly and the bacterial load decreased significantly after aPDT. Conclusion: Photoexcited AgSD-NLs@Cur has an antimicrobial potential against A. baumannii.

ADAM10 (a disintegrin and metalloproteinase-10) is a known sheddase for EGFR (epidermal growth factor receptor) ligands and has been suggested to modulate angiogenesis. We aimed to evaluate the expression of ADAM10 in patients with oral squamous cell carcinoma (OSCC) and to determine its correlation with EGFR, CD105 and clinicopathologic parameters. Fifty primary OSCCs with clinical data were graded according to the histologic risk assessment (HRA) model and subjected to immunohistochemical staining using antibodies against ADAM10, EGFR1 and CD105. ADAM10 was assessed in both epithelial and stromal components. The associations among all three proteins and clinicopathologic factors including tumor size, lymph node status and distant metastasis (TNM) were statistically analyzed (P 0.05). Epithelial-ADAM10, stromal-ADAM10 and EGFR were overexpressed in 92%, 40% and 56% of the OSCCs, respectively. EGFR expression occurred in peripheral and diffuse patterns, which were also separately considered in our analyses. A significant correlation was found between ADAM10 and CD105 (r = -0.455; P 0.001). Lymphocytic infiltration scores (P = 0.04) and tumor size (P = 0.001) showed significant differences between EGFR+ and EGFR- tumors, but none of the other variables had any relationships with either clinicopathologic factors or each other (P 0.05). ADAM10 was upregulated in OSCC but had no correlation with survival-associated factors such as TNM or the HRA model. At the protein level, epithelial ADAM10 negatively regulated neoangiogenesis, but its interaction with EGFR was minimal. Reduction in host immunologic responses was associated with a decrease in EGFR. These findings, if corroborated, could be interesting in combination therapies used for cancer treatment.

Introduction: Due to the increasing prevalence and high mortality rate of oral squamous cell carcinoma (OSCC) and problems with its routine treatments, more recent modalities like photodynamic therapy (PDT) have been developed. PDT effectively destroys tumor cells with minimum side effects. Research on in vitro effects of PDT may be helpful in determining the molecular mechanisms responsible for its effectiveness and can lead to the development of more efficient techniques. The aim of this study was to review the use of PDT in OSCC among in vitro studies. Methods: A literature search for English articles on PDT in OSCC was performed in PubMed, Scopus, Google Scholar, and Web of Science. Data were extracted based on the inclusion/exclusion criteria, which were detailed using the PICO framework: all eligible in vitro studies evaluating the effects of PDT on the viability of OSCC compared to controls without PDT were included. Results: Forty-one out of 567 studies were selected. The tongue was the most common OSCC site, 5-aminolevulinic acid was the most used photosensitizer (PS), cell viability/toxicity and apoptosis were the most evaluated outcomes, and lasers with wavelengths of 600-700 nm were the most common light sources and wavelengths respectively. Conclusion: PDT showed promising effects on reducing the viability of OSCC cells. Cell lines from various sources or even those originating from the same location sometimes responded differently to the same protocol. Considering the favorable results obtained from natural PSs and regarding their additional health-promoting properties, their use in future investigations with different cell lines and light specifications is recommended.

The COVID-19 pandemic has led to many problems in cancer patients, which in part are due to insufficient knowledge of the exact implications of the virus on these individuals. Perceptions based on known facts about previous pandemics and coronaviruses might not agree with actual real-life experience and objective findings. We present a compilation of scientific facts and actual observations on different aspects of SARS-CoV-2 infection in cancer patients. These patients are at increased risk of viral contraction and have higher chances of severe disease/mortality. The latter is impacted by other factors and is still debated. In contrast to preliminary impressions, the benefits of anti-cancer treatments outweigh their risks and should be continued. Cancer patients generate antibodies in response to vaccination but in lower amounts than healthy people, especially those with hematologic cancers. Boosters, including third doses, have shown increased immune-responses in most patients. Vaccination should be prioritized in these individuals.

Diffuse large B-cell lymphoma (DLBCL) harbors defects in the proliferation pathway. We performed multiparameter analysis of proteins expressed during different cell cycle phases and correlated them with clinical parameters of head and neck DLBCLs.Thirty-nine DLBCLs were staged and immunohistochemically stained with MCM2, Ki67, and geminin. The receiver operating characteristic curve and its area under the curve were calculated, and sensitivity vs specificity curve analysis was performed.The highest labeling index was in MCM2, followed by Ki67 and geminin (P.001). All pairs showed significant differences (P.001). The best cutoff points to differentiate limited from advanced disease were 68% and 45% for MCM2 and Ki67, respectively. There was no acceptable cutoff for geminin (area under the curve = 0.667, P = .134). MCM2/Ki67 (P = .293) and geminin/Ki67 (P = .233) ratios did not differ between the stages. The median (interquartile range) of the geminin/Ki67 ratio was 0.57 (0.68), translating to a reduced G1.We suggest a role for cell cycle-related proteins in the biology and behavior of DLBCLs. MCM2 and Ki67 cutoffs can be a potential option to differentiate limited from advanced disease, where imaging and laboratory techniques are unavailable. The G1 decrease and the significantly higher MCM2 expression compared to Ki67 indicate replication disturbances, making factors involved in the G1 phase targets for treatment.

The pathogenic mechanism of SARS-CoV-2 infection is unclear, and its symptoms vary in different patients. Initial reports of COVID-19 concentrated on pulmonary issues, but with time, additional features such as hyposmia/anosmia, dysgeusia, and skin lesions were added to the list of COVID-19 symptoms. There have been an increasing number of reports on oral cavity lesions in individuals with COVID-19, which might be relevant considering that this location is one of the first sites coming into contact with the virus and that it contains the SARS-CoV-2 receptor. We hereby aim to familiarize practicing head and neck clinicians with the range of oral lesions reported in COVID-19 patients and to critically appraise the most recent data on the role of SARS-CoV-2 in these lesions. We also discuss the ongoing debate on the direct/indirect association of oral symptoms with the disease. COVID-19 cases with simultaneous oral symptoms were extracted from the literature, and articles discussing the role of SARS-CoV-2 in oral lesions were compiled and methodically analyzed. We found approximately 95 COVID-19 patients with a wide range of oral lesions. Based on current evidence, the exact role of SARS-CoV-2 in the development of oral lesions remains unclear. Oral examination of patients is needed to provide adequate cases for analysis to clarify unknown problems related to COVID-19. There is evidence to support both the direct and indirect roles of SARS-CoV-2 in the development of oral lesions. Awareness of the possibility of oral manifestations in COVID-19 is important to clarify the range of disease signs and symptoms.

Potentially malignant disorders are one of the clinical challenges. Dysplasia in these lesions can be a predictor of more potential for malignant changes. Photo-bio-modulation in benign lesions has advantages, but there is doubt on its safety in potentially malignant lesions. This study aims to assess if low-level laser can promote dysplastic changes while the method can play an important role in management of dysplastic lesions. Dysplasia was induced on anterior wall of the buccal pouch of 80 young Syrian male hamsters. Then, hamsters were divided to four groups to receive 4 and 12 sessions irradiation of 660 and 810 nanometers low-level lasers. For histopathologic study of the tissue, we used light microscopes. Using SPSS, data were analyzed via Wilcoxon signed rank test and Mann-Whitney U-test. In all of our four groups, the severity of dysplasia had no statistical difference in study sides comparing with their own controls. Wavelength and numbers of laser irradiation sessions had no statistically meaningful effect on the severity of dysplasia either. Low-level lasers appear to show no relevant or significant effect over the aggravation of the dysplasia's severity. Neither the wavelength nor the number of sessions appear to have any impact in the results.

Background Non-invasive sonodynamic therapy (SDT) is a new treatment modality that uses low-intensity ultrasound to activate a non-toxic sensitizing chemical agent for cancer therapy in a site-directed manner. This study aimed to investigate the anti-cancer effects of ultrasound combined with nano emodin transfersome (NET) on head and neck squamous cell carcinoma (HNSCC) cell lines. Materials and methods A transfersome form of nano emodin as a novel sono-responsive nanomaterial was synthesized to enhance the accumulation and penetration of nanoparticles. iIn vitro experiments including hemolytic activity, cell proliferation, intracellular reactive oxygen species (ROS) generation, apoptosis induction, DNA fragmentation, and mRNA expressions of caspase 3 and 9 were conducted to explore the anti-cancer effects of NET-SDT on FaDu and CAL-27 cell lines. Results Characterization tests showed the round and uniform morphology of NET with transfersome structure, resulting in a high drug-loading content and encapsulation efficiency. No significant hemolytic activity was observed (P > 0.05). Cytotoxicity gradually increased with increasing concentrations of NET, so that 10 × 10–4 g/L of NET plus 5 min ultrasound irradiation at a frequency of 1 MHz and ultrasonic intensity of 2 W/cm2 effectively killed 98.2 % and 97.3 % of FaDu and CAL-27 cell lines, respectively (P Conclusions Our data demonstrated that SDT with NET as a sonosensitizer can induce apoptosis and significantly decrease cell viability of HNSCC cell lines, which represents the role of NET-SDT as a potent anti-cancer modality.

Despite the similarities between oral and esophageal squamous cell carcinomas (SCCs), the survival rate of this cancer is relatively low in the esophagus compared to the oral cavity. To our knowledge, mast cells and angiogenesis have not been simultaneously compared between oral and esophageal SCCs. However, they have been separately evaluated in each of these locations with conflicting results. Therefore, the aim of this study was to assess and compare mast cell count and microvessel density between SCCs of the esophagus and oral cavity. A total of 46 oral and esophageal SCCs (23 of each) were stained immunohistochemically and histochemically with CD31 and methylene blue, respectively. Statistical analysis was performed using t-test, one-way ANOVA, and Pearson correlation analysis. Microvessel density was significantly higher in oral compared to esophageal tumors (P=0.02). Conversely, esophageal SCCs showed significantly higher mast cell counts than that of oral neoplasms (P=0.04). Pearson correlation analysis showed no association between these two factors in either oral SCC (P=0.51) or esophageal SCC (P=0.34). A significant difference between mean mast cell count and microvessel density in oral and esophageal SCC may be related to inherent differences in the tissues of origin and might, to some extent, be responsible for the different biological behaviors of these cancers. © 2019 Tehran University of Medical Sciences. All rights reserved. Acta Med Iran 2019;57(10):575-580.

Background Induction of podoplanin by transforming growth factor-β (TGF-β) has been shown in a number of lesions but not in odontogenic tumors (OTs). We evaluated the association between these markers in OTs for the first time and compared their expression among the different neoplasms. Methods Immunohistochemistry using monoclonal antibody against podoplanin and TGF-β was performed on 76 odontogenic cysts and tumors. Spearman's correlation coefficient, Kruskal-Wallis, and Mann-Whitney U tests followed by adjustment with Bonferroni were used for statistical analysis (P Results A significant difference in podoplanin expression was found among the lesions consisting of solid ameloblastomas, adenomatoid odontogenic tumors, ameloblastic fibromas, odontogenic myxomas (OMs), odontogenic keratocysts, and calcifying odontogenic cysts. Significant differences were observed only between OMs and each of the other neoplasms. Podoplanin immunostaining in the connective tissue was absent in most lesions. TGF-β was significantly different among the study sample but not between the lesions in paired comparisons. None of the studied OTs showed significant correlations between podoplanin-TGF-β, in either the epithelium or the stroma. These markers were also descriptively reported in calcifying epithelial odontogenic tumors. Conclusions The inductive effect of TGF-β on podoplanin seems to be limited, if any, in odontogenic lesions. Podoplanin appears to play a role in some aspects of OTs with epithelial or mixed origins. Despite the possible participation of podoplanin in tumorigenesis, it may not necessarily be involved in the aggressive behavior of OTs.

Chronic liver disease (CLD) affects millions of people and its impact on bone loss has become a subject of interest. Nitric oxide and endogenous opioids are suggested to increase during cholestasis/cirrhosis and may impact bone resorption by different mechanisms. The receptor activator of nuclear factor-κB (RANK)/RANK-ligand (RANKL)/osteoprotegerin (OPG) signaling pathway regulates bone resorption, but its role in metabolic bone disease subsequent to CLD is unknown. We aimed to investigate the involvement of nitrergic and opioidergic systems in bone loss relative to the RANK/RANKL/OPG pathway, in bile duct-ligated (BDL) rats. Eighty BDL/sham-operated (SO) rats received injections of 3 mg/kg/day Nω-Nitro-L-arginine methyl ester ± naltrexone (10 mg/kg/day) or saline for 28 days. Plasma bone turnover markers, OPG, RANK, and RANKL along with mRNA expression levels of the latter three were assessed. Plasma bone turnover markers and OPG level increased, but RANKL decreased in the BDL group compared with their SO controls (both: P ≤ 0.05). Administration of naltrexone reduced bone turnover markers and OPG level while increased RANKL content in comparison to BDL rats (P ≤ 0.05). As compared to untreated BDL rats, nitric oxide inhibition showed no effect on bone turnover marker i.e. OPG, RANK, and RANKL levels. BDL significantly increased RANK mRNA, but had no significant effect on RANKL and OPG mRNA expression. The lack of association between plasma levels and quantitative gene expression of RANKL and OPG suggests an indirect function of these markers in BDL rats. Considering that opioid receptor blockage by naltrexone in BDL animals caused a significant decrease in OPG and an increase in RANKL plasma contents, it could be postulated that the opioidergic system may have a regulatory effect on these bone markers.

In recent years, the therapeutic application of botulinum neurotoxin (BoNT) has expanded to encompass a variety of issues beyond its well-known usage for hyperkinetic movement disorders, autonomic hyperactivity, and facial rejuvenation. Dentistry is one of the fields that has benefited greatly from botulinum toxin therapy, as evidenced by multiple clinical trials which provided evidence for usefulness of this mode of therapy in common issues encountered in the field of dentistry (described in Chap. 16). In this chapter, the future potentials for BoNT therapy in the field of dentistry and its use in oral and maxillofacial region with its rich network of nerves and muscles are described. In addition, this chapter focuses on preclinical and preliminary studies on the effect of intramuscular injections of BoNT on craniofacial growth and proposes the possibility of using this toxin to influence the dentofacial complex during growth. Existing data or suggestions on the use of BoNT in implant dentistry, tongue thrust, temporomandibular joint dislocation, bone/plate fractures, herpes simplex virus, angular cheilitis, and burning mouth syndrome are also presented.

Introduction: Proliferation markers play a significant role in the biologic behavior of tumors. Geminin is a known inhibitor of the cell cycle and DNA replication and has not been previously reported in cutaneous basal and squamous cell carcinomas of the head and neck. Objectives: We aimed to investigate proliferation markers ki67, MCM2, and geminin in head and neck cutaneous basal and squamous cell carcinomas. Methods: Forty cases of each tumor were immuostained with ki67, MCM2, and geminin followed by assessment of labeling indices (LIs). MCM2/ki67- and geminin/ki67-ratios were also determined; t-test was used for statistical analysis (p

Aims Allergic rhinitis is a global cause of disability, characterized by airway inflammation. Sumatriptan is a 5-hydroxytryptamine 1B/1D (5HT1B/1D) agonist used as a treatment for migraine headaches. Activation of 5HT1B/1D receptors can inhibit the release of neuropeptides and inhibit the inflammation cascades. This study investigated the effect of sumatriptan on ovalbumin-induced allergic rhinitis model in mice and the role of nitric oxide. Methods Female Balb/c mice were sensitized by intraperitoneal ovalbumin and challenged by intranasal ovalbumin. Mice received sumatriptan in doses 3, 10, 30 μg/kg intraperitoneally, 30 min before the last ovalbumin challenge. Key findings Intraperitoneal injection of sumatriptan significantly decreased the nasal scratching, IL-4 and serum IgE levels of allergic mice, but it increased IFNγ levels. Histopathological analysis showed that the number of eosinophils was significantly elevated in nasal mucosa of ovalbumin-induced allergic mice, while sumatriptan treatment significantly reduced the number of eosinophils. GR-127935, a selective 5-HT1B/1D-receptor antagonist, reversed the anti-allergic effects of sumatriptan. Acute administration of l -NAME, a non-specific inhibitor of nitric oxide synthase, along with sumatriptan attenuated the anti-allergic effects of sumatriptan but chronic administration of l -NAME did not affect the influences of sumatriptan. Furthermore, sumatriptan decreased the inducible nitric oxide synthase (iNOS) protein expression in allergic mice, but it did not change the concentration of eNOS protein. Significance This study shows that sumatriptan administration is associated with anti-allergic effects which are through 5HT1B/1D receptors. Decrease in iNOS expression and changes in T-helper 1&2 cytokines levels may indicate the involvement of inducible NOS and inflammation.

Squamous cell carcinoma (SCC) is a relatively common cancer with a low survival rate, poor prognosis and no effective treatment strategy. The use of cell-free conditioned media derived from mesenchymal stem cells (CM-MSCs) has shown promising results in treating various diseases. This study aimed to evaluate the effects of CM-MSCs on proliferation and apoptosis of CAL-27 and FaDu SCC cell lines. CM derived from human bone marrow and human amniotic membrane MSCs (BM-MSCs and AM-MSCs) was used in this investigation. MTT assay demonstrated that CM-BMMSC decreased the viability of CAL-27 and FaDu cell lines, 24, 48, and 72 h after treatment. Quantitative real-time PCR indicated that mRNA expression of PCNA as a proliferative marker, and BCL-2 as an anti-apoptotic protein, decreased in both cell lines treated with CM-BMMSC. Based on the flow cytometry results, the number of positive proliferative Ki67 cells and apoptotic Annexin-V cells decreased and increased in both cell lines treated with CM-BMMSC, respectively. However, CM-AMMSC treatment had both pro-and anti-neoplastic effects in our samples and showed considerable differences between the two cell lines. Taken together, our findings demonstrated that CM-BMMSC and, to a lesser degree, CM-AMMSC decrease cell viability and proliferation and increase cell apoptosis in SCC cell lines in a time-dependent manner. However, further studies are needed, especially to evaluate the anti-tumor potential of CM-BMMSC in vivo.

The aim of the present study was to evaluate angiogenesis, lymphangiogenesis, and mast cell density in association with the histologic risk assessment (HRA) model in oral squamous cell carcinoma. One hundred oral squamous cell carcinomas were graded according to the HRA system and immunostained with antibodies against D2-40, CD34, and CD105 to determine lymphvessel density (LVD) and microvessel density (MVD). Mast cells were detected by toluidine blue and counted in all samples. Assessments were made between the evaluated factors and the histologic variables of HRA. Kruskal-Wallis and Mann-Whitney U test were used for statistical analysis and P0.05 was considered significant. There were 32, 26, and 42 cases of low, intermediate, and high-grade neoplasms, respectively. Only LVD (P=0.05) and CD34MVD (P=0.03) showed significant associations with lymphocytic infiltration and were both higher in score 0 cases compared with score 3 tumors (P=0.05 and0.001, respectively). None of the other variables showed significant relationships with the HRA risk scores or subcategories (P0.05). According to our findings, it appears that the role of lymphangiogenesis and angiogenesis is limited in the HRA system. The significant relationship of lymphocytic infiltration with LVD and CD34MVD, but not CD105MVD, might indicate that "inflammatory lymphangiogenesis/angiogenesis" may differ from that induced by noninflamed neoplastic tissues. It also seems that the vasculature in inflamed tumor tissues is not entirely newly formed.

Background and Aim: Captopril is an oral angiotensin-converting-enzyme (ACE) inhibitor extensively used in the treatment of hypertension and heart failure. ACE has been suggested to function in bone cells and might therefore impact orthodontic tooth movement (OTM). Considering the controversy surrounding the effects of ACE and its inhibitors on osseous tissues, we aimed to evaluate the effect of captopril on OTM for the first time in a rat model. Materials and Methods: Orthodontic appliances were fixed between the left first molars and incisors of 30 rats divided into three groups (n=10) receiving captopril, saline or no treatment. Following sacrifice on day 21, the amount of tooth movement was measured as the distance created between the first and second molars. Bone density was assessed by lateral cephalograms on days 1 and 21 and osteoclast number, root resorption and periodontal ligament (PDL) width were analyzed histologically. One-way ANOVA followed by post-hoc test were used for statistical analysis (P

Phosphatidylserine nanocochleates (Nanocochs) are novel delivery systems that may play a prominent osteoprotective role with their cargo, vitamin D3 (Vit-D3), against osteoporosis. Therefore, this study was conducted to characterize a Nanococh containing vitamin D3 (Nanococh-D3) and investigate its potential role in improving GIO in a rat model. Roll-shaped Nanococh-D3 particles were obtained in a size range of 320 nm with a sustained release performance. Oral Nanococh-D3 significantly increased the bioavailability of Vit-D3, enhanced bone mechanical strength, and improved osteogenic biomarkers including B-ALP, osteocalcin, Ca, and OPG in GIO rats. This formulation markedly suppressed gene expression of RANK and RANKL in treated rats. Histomorphometric analysis showed significant repairs in bone tissues and TRAP staining indicated a significant decrease in osteoclasts using Nanococh-D3 in osteoporotic rats. Nanococh alone similar to Nanococh-D3 acted better than AL as a standard anti-osteoporotic drug in the improvement of bone strength. In conclusion, our results established the potential role of Nanococh-D3 against osteoporosis in rats.

The present study aimed to investigate the effects of phosphatidylserine liposomes (PSLs) and phosphatidylserine liposomes containing alendronate (AL-PSLs) on the improvement of methylprednisolone (MP) induced osteoporosis in a rat model. AL-PSLs formulation was prepared, characterized, and evaluated in different pH media to simulate gastrointestinal condition. Osteoporosis was induced by 3 weeks oral administration of MP (10 mg/kg) and then treatment by PSLs, AL-PSLs, and alendronate (AL). Bone metabolic and biomechanical markers were measured in treated rat groups. Also, Tartrate-resistant acid phosphatase (TRAP) staining and histomorphometry were evaluated on bone tissues of treated rats. AL-PSLs were obtained in a size range of 155 nm and negatively surface charge with an entrapment efficiency of 42%. The AL leakage from AL-PSLs did not exhibit a significant difference in acidic or basic media in comparison with the neutral condition. The concentrations of calcium, osteocalcin, bone alkaline phosphatase, and osteoprotegerin (OPG) of serum were significantly increased in PSLs and AL-PSLs treated groups compared to the MP group. Also, PSLs and AL-PSLs significantly improved the thickness and volume of the cortical and trabecular bone mass in treated groups. In addition, TRAP staining indicated a significant decrease of osteoclast number in osteoporotic rats treated with AL-PSLs and PSLs. In this study, AL-PSLs and even PSLs alone made a potential bone mechanical strength in glucocorticoid-induced bone loss more than AL in rats. In conclusion, our findings suggest that PSLs consumption with or without an anti-osteoporotic drug might be an applicable choice in control of osteoporosis.

Alzheimer's disease (AD) is closely associated with neuroinflammation development in the brain. Co-delivery of metformin (MET) with phosphatidylserine liposomes neuroprotectant may be beneficial in ameliorating AD-related symptoms like memory impairment and inflammation. Therefore, we aimed to prepare metformin containing phosphatidylserine nanoliposomes formulation (MET-PSL) and to evaluate its effect on rats subjected to AD. Alzheimer's disease model was induced by bilateral intracerebroventricular injection of streptozotocin (3 mg/kg) into rat brains using the stereotactic technique. MET-PSL, MET, and PSL alone were administered intraperitoneally to AD-induced animals and factors including learning and memory storage in addition to cytokine and tissue inflammatory changes were evaluated after a 22-day experiment period. The learning and memory parameters significantly (P 0.05) improved in AD-rats treated with MET-PSL. Moreover, MET-PSL administration significantly (P 0.05) decreased cytokine levels of IL1-β, TNF-α, and TGF-β in hippocampal tissues of rats with AD. Histological results indicated a considerable reduction in inflammatory and necrotic neural cells along with significantly (P 0.05) increased neurogenesis in MET-PSL treated rats. Furthermore, our results showed that MET-PSL formulation could potentially act better than the free form of MET and PSL alone in the recovery process of rats with AD. In general, our data suggest that combination therapy of metformin loaded phosphatidylserine liposomes may enhance the therapeutic performance in AD patients of a clinical study.