A versatile theranostic magnetic polydopamine iron oxide NIR laser-responsive nanosystem containing doxorubicin for chemo-photothermal therapy of melanoma.

Theranostics nanoparticles (NPs) have recently received much attention in cancer imaging and treatment. This study aimed to develop a multifunctional nanosystem for the targeted delivery of photothermal and chemotherapy agents. Fe3O4 NPs were modified with polydopamine, bovine serum albumin, and loaded with DOX via a thermal-cleavable Azo linker (Fe3O4@PDA@BSA-DOX). The size of Fe3O4@PDA@BSA NPs was approximately 98 nm under the desired conditions. Because of the ability of Fe3O4 and PDA to convert light into heat, the temperature of Fe3O4@PDA@BSA NPs increased to approximately 47 °C within 10 min when exposed to an 808 nm NIR laser with a power density of 1.5 W/cm2. The heat generated by the NIR laser leads to the breaking of AZO linker and drug release. In vivo and in vitro results demonstrated that prepared NPs under laser irradiation successfully eradicated tumor cells without any significant toxicity effect. Moreover, the Fe3O4@PDA@BSA NPs exhibited the potential to function as a contrasting agent. These NPs could accumulate in tumors with the help of an external magnet, resulting in a significant enhancement in the quality of magnetic resonance imaging (MRI). The prepared novel multifunctional NPs seem to be an efficient system for imaging and combination therapy in melanoma.

The effects of combined and independent low-level laser and mesenchymal stem cell therapy on induced knee osteoarthritis: An animal study.

BACKGROUND: Mesenchymal stem cell (MSC) injection has emerged as a novel treatment for knee osteoarthritis (OA). In addition, low-level laser therapy (LLLT) has been reported to delay the progression of OA. Thus, the current study on animal models of OA investigated the effectiveness of these methods when administered independently and combined. METHODS: Twenty-five guinea pig models of OA were randomly sorted into five study groups. The test groups received intra-articular MSC, LLLT, and a combination of these therapeutics for 8 weeks. Radiological and histopathologic evaluations were carried out for the test groups and the control after the completion of treatments. RESULTS: The MSC-treated groups showed better outcomes in terms of all radiological and histological indexes compared with the control, apart from subchondral bone (P < 0.05). Similarly, but to a different extent, the LLLT-treated group showed better results than the controls (P < 0.05). The combination of MSC therapy and LLLT improved the cartilage, surface, matrix, space width, osteophytes, and radiologic OA scores more effectively than each of these methods alone (P < 0.05). CONCLUSIONS: According to our results, the combination of intra-articular MSC and LLLT can effectively improve OA in animal models. Further preclinical and clinical studies are recommended to assess the effectiveness of these therapeutics alone and in combination.

Protective effect of Melissa officinalis against acetic acid-induced ulcerative colitis in rat models: an experimental study.

Background: Inflammation and oxidative activities within the gut play major roles in the pathogenesis of ulcerative colitis (UC). We aimed to determine the effect of Melissa officinalis, an antioxidant and anti-inflammatory agent, on the colon histological characteristics in acetic acid (AA)-induced UC in rat models. Methods: Thirty-six male rats with AA-induced colitis were divided into 5 groups: no treatment (AA); daily treatment with 300 mg/kg Melissa officinalis orally (MO) and rectally (MR); and 100 mg/kg mesalamine orally (AO) and rectally (AR). Macroscopic and histopathological evaluation of the colon, along with a biochemical laboratory evaluation, were performed 10 days after UC induction. Results: All treatment groups demonstrated lower macroscopic grading scores compared to the AA group. After treatment with MO, 42.9% of cases demonstrated no macroscopic changes, while 14.3% demonstrated only mucosal erythema. In the MR group 28.6% of rats had no changes in their mucosal lining and 28.6% had only mucosal erythema. Following histopathological evaluation, the AO group had lower scores regarding the severity of ulcer, inflammation, destruction, crypt abscess, and disorganization compared to the MO group. (P=0.02) The MR group demonstrated lower microscopic scores compared to the MO group, and also lower macroscopic scores compared to the AR group, although not significantly (P>0.05). Conclusions: Both oral and topical administration of Melissa officinalis have satisfactory healing properties compared to mesalamine, with topical route having better results. Therefore, further studies are needed to establish the benefit of Melissa officinalis administration (both orally and topically) within a UC treatment protocol.

In vitro and in vivo anticancer activity of mebendazole in colon cancer: a promising drug repositioning.

Colon cancer is one of the most common cancers and one of the main causes of death worldwide. Therefore, new treatment methods with better efficiency and fewer risks are very necessary. Mebendazole (MBZ), a drug commonly used for helminthic infections, has recently received attention as a suitable candidate for the treatment of various cancers. This study aimed to investigate, in vitro and in vivo, anticancer activity and selectivity Index of MBZ on colon cancer. HT-29 (human colorectal adenocarcinoma) and MCF-10 (non-tumorigenic epithelial) cell lines were treated with MBZ and Doxorubicin (DOX; positive control drug). IC50 values were estimated using methyl thiazole diphenyl-tetrazolium bromide (MTT) assay. We employed flow cytometry using annexin V-FITC and propidium iodide dyes. For the animal study, colon cancer was subcutaneously induced by CT26 cells (mouse colon cancer) in Bulb/C mice. The mice were treated with 0.05 of LD50, intraperitoneal, every other day for 35 days. Finally, the survival rate, tumor volume, and tumor weight were calculated. Our results demonstrated that IC50 values after 72 h for HT29 and MCF-10 cell lines were 0.29 ± 0.04 µM and 0.80 ± 0.02 µM, respectively. MBZ was more selective than DOX in inhibiting the proliferation of cancer cells compared to normal cells (2. 75 vs. 2.45). Annexin V/PI staining demonstrated that MBZ treatment at IC50 concentrations induced (78 ± 12%) apoptosis in the HT29 cancer cell line after 48 h (P ≤ 0.0001). Also, in mice bearing colon cancer, MBZ significantly reduced the tumor volume (1177 ± 1109 mm3; P ≤ 0.001) and tumor weight (2.30 ± 1.97 g; P ≤ 0.0001) compared to the negative control group (weight 12.45 ± 2.0 g; volume 7346 ± 1077). Also, MBZ increases mean survival time (MST) and increase life span (ILS) percentage in the animal study (51.2 ± 37% vs 93%, respectively). This study suggests that mebendazole strongly and selectively inhibits proliferation and induces apoptosis in colon cancer cells. It may be, accordingly, a promising drug for clinical research and application.

Dendritic hybrid materials comprising polyhedral oligomeric silsesquioxane (POSS) and hyperbranched polyglycerol for effective antifungal drug delivery and therapy in systemic candidiasis.

Systemic Candida infections are routinely treated with amphotericin B (AMB), a highly effective antimycotic drug. However, due to severe toxicities linked to the parenteral administration of conventional micellar formulations (Fungizone®), its clinical utility is limited. Hyperbranched polyglycerols (HPGs) are multi-branched three-dimensional hydrophilic macromolecules that can be used to lessen the toxicity of AMB while also increasing its aqueous solubility. In the current research, to improve the safety and therapeutic efficacy of AMB, we developed new polyhedral oligomeric silsesquioxane - hyperbranched polyglycerol dendrimers with cholesterol termini (POSS-HPG@Chol) using azide-alkyne click reaction. Compared with Fungizone®, the as-synthesized POSS-HPG@Chol/AMB had lower minimum inhibitory and fungicidal concentrations against almost all studied Candida spp., as well as much less hemolysis and cytotoxicity. POSS-HPG@Chol/AMB revealed total protection of Balb/C mice from severe Candida infections in an experimental model of systemic candidiasis and can effectively reduce or eliminate AMB liver and kidney tissue injuries. Thanks to their safety, biocompatibility, and unique therapeutic properties, the developed POSS-polyglycerol dendrimers could be viable nanostructures for the delivery of poorly soluble drugs like AMB.

Evaluation of the topical gel and oral administration of Punica Granatum Var Pleniflora on oral mucositis induced by 5-Fluorouracil in golden hamsters.

BACKGROUND: Oral mucositis (OM), an acute inflammation of the oral cavity, is a common complication in patients undergoing invasive myeloblastic chemotherapy or radiation therapy. 5-fluorouracil (5-FU) is one of the most effective therapeutic drugs, but one of the common side effects of 5-FU administration is OM. Unfortunately, no suitable treatment has been found, so far to control its side effects. Studies showed that herbal medicine like Punica granatum var pleniflora (PGP) has medicinal properties such as anti-inflammatory and antibacterial and can be an alternative for the treatment of fungal infection. Accordingly, we decided to investigate the therapeutic effect of PGP in the treatment of OM caused by 5-FU in golden hamsters. METHODS: Sixty male golden hamsters were divided into six main group. Chemotherapy with 5-FU at dose of 60 mg/kg was performed at a ten-day duration. Then, cheek pouches of the hamsters were scratched with an 18-gauge sterile needle to induce oral mucositis in animals. On the twelfth day, as a day of intensification of OM, treatment with PGP including topical gel with concentrations of 5% and 10% and oral administration of hydro-alcoholic extract with doses of 125 mg/kg and 250 mg/kg for three- and five-day therapeutic duration were separately started. Finally, samples of cheek pouches in hamsters were collected on 14th and 17th days and histopathologic score (HPS), malondialdehyde (MDA), and myeloperoxidase (MPO) levels were assayed. RESULTS: A significant (p < 0.05) decrease in histopathologic score was observed in G10%-, P125-treated groups in comparison to the Ctrl group. Our data showed that treatment with G10% is more potent than P125-treated group. In contrast, histopathologic score in G10%, P125, and P250 treated groups demonstrated almost similar values On the 17th day. However, the levels of MDA and MPO in the treatment groups were enhanced compared with control group (p < 0.05). CONCLUSIONS: It is possible that PGP can play protective role in the healing of tissue damage caused by chemotherapy with 5-FU due to the presence of its natural compounds and antioxidant properties.

Hydroalcoholic extract of Glycyrrhiza glabra root combined with Linum usitatissimum oil as an alternative for hormone replacement therapy in ovariectomized rats.

Objective: Plant-derived estrogens (phytoestrogens) with structural similarity to primary female sex hormones could be suitable replacements for sex hormones. Therefore, the effects of the licorice root extract and Linum usitatissimum oil on biochemical and hormonal indices in the serum and uterine stereological changes in ovariectomized rats were evaluated. Design: In this study, 70 adult female rats were randomly divided into seven groups including 1) control group, 2) sham-operated group, 3) ovariectomized (OVX) group, 4) OVX rats that received 1 mg/kg estradiol for 8 weeks at the day of post-operation, 5) OVX rats which received 2.0 mg/kg body wt Linum usitatissimum oil for 8 weeks at the day of post-operation, 6) OVX rats which received 2.0 mg/kg body wt licorice extract for 8 weeks at the day of post-operation, and 7) OVX rats which received 2.0 mg/kg body wt Linum usitatissimum oil + 2.0 mg/kg body wt licorice extract for 8 weeks at the day of post-operation. After eight weeks, alkaline phosphatase activity, as well as calcium, estradiol, and progesterone concentrations were assessed and tissue samples of the uterus were serologically examined. Results: The results indicated that after 8 weeks of OVX the alkaline phosphatase activity (Mean = 637.7 IU/L) increased and the calcium (Mean = 7.09 mg/dl), estradiol (5.30 pmol/L), and progesterone (Mean = 3.53 nmol/L) reduced compared to other groups. Moreover, stereological changes in the uterus in ovariectomy groups were seen compared to the other groups. The treatment with Linum usitatissimum oil and licorice extract had a significant therapeutic effect on biochemical factors and stereological changes compared to the ovariectomized group. Conclusion: The results of this study showed that the combination of Linum usitatissimum oil with licorice extract showed the high potential of hormone replacement therapy in the reduction of OVX complications.

Comparing the healing properties of intra-articular injection of human dental pulp stem cells and cell-free-secretome on induced knee osteoarthritis in male rats.

OBJECTIVE: Osteoarthritis (OA) is a common and painful joint disease with multifactorial causes. Stem cells, due to their high ability to reproduce and differentiate, have created a new horizon in tissue engineering of cartilage and bone. Secretions are one of the new therapies that can be used with stem cells or separately. This study aimed to compare the healing effects of human dental pulp stem cells, cell-free secretome, and human dental pulp mesenchymal stem cells with secretome in the induced OA in male rats. METHODS: Dental pulp mesenchymal stem cells were isolated and prepared from human dental pulp. The collagenase type II was injected into the knee of twenty-five male Sprague-Dawley rats, and after 10 weeks, OA was confirmed. Rats were divided into five groups (n = 5): 1) Human dental pulp stem cells plus secretome (HDP+Sec); 2) Human dental pulp stem cells (HDP); 3) Secretome (Sec); 4) Hyalgan as the positive control (Hya); 5) No treatment as the negative control (Ctrl). After 12 weeks since OA was confirmed, the healing process was examined by histopathology and radiology evaluations. RESULTS: Histopathological evaluations, radiological assessments, and matrix indexes in three treatment groups significantly improved compared to the Ctrl and Hya groups. Surface in HDP+Sec was significantly better than the Ctrl group. In radiological evaluations, a significant decrease in OA was observed in the three treatment groups in comparison with the Ctrl groups. There was no significant difference between the treatment groups in any radiological and histopathological evaluations. HDP + Sec group slightly records better results compared to Sec or HDP treatment groups. CONCLUSION: It was concluded that human dental pulp stem cells and their secretome promote cartilage regeneration due to their cell protective potential as well as matrix degeneration reduction capacity.

Investigating the Effect of Hydroalcoholic Extract of Licorice Root to Prevent Ovariectomy-Mediated Complications.

Introduction: The importance of women's health and the quality of life after menopause is a critical issue. To prevent disability and menopause complications as well as avoid the side effects of hormone replacement therapy (HRT), in this study, licorice hydroalcoholic extract (Glycyrrhiza uralensis roots) was evaluated as a natural remedy. Methods: Seventy-two female Sprague-Dawley rats were divided into six groups: control group, Sham-operated group, Glycyrrhiza (Gly) 30% group, and ovariectomized group as well as two ovariectomized groups treated with Gly 10% and Gly 30%. Normal saline and different treatments were administered orally for 8 weeks. At the end of the study, calcium, alkaline phosphatase, estrogen, and progesterone levels in the ovariectomized rats were determined. Moreover, the stereological and histopathological changes in uterine tissue in all groups were determined. Phytochemical analyses were also performed to determine the total phenolic content and antioxidant potential of the extract. Result: The hydroalcoholic extract of licorice root exhibited considerable effect to improve calcium, estrogen, and progesterone levels in the ovariectomized rats. Also, hydroalcoholic extract of licorice root successfully decreases the amount of alkaline phosphatase (ALP) level. The stereological and histopathological findings confirmed the therapeutic potential of this extract. The considerable effects of hydroalcoholic extract of licorice root could be due to high amounts of phytoestrogens with similar estrogen-like structures. Considerable total phenolic content and antioxidant activity were also seen in licorice root extract. Conclusion: Hydroalcoholic extract of licorice root due to containing high amounts of phytoestrogens with similar chemical structures to estradiol notably improves biochemical parameters as well as stereological and histopathological markers of uterine tissues in ovariectomy rats, so it could be a potential agent for prevention and/or treatment as hormone replacement therapy in healthy middle-aged and/or older women.

The effect of hydroalcoholic extract of Psidium guajava L. on experimentally induced oral mucosal wound in rat.

BACKGROUND: The aim of this study was to evaluate the biological effects of hydroalcoholic extract of Psidium guajava L leaves and phenytoin as a standard agent on the induced oral mucosal wound. METHODS: Hundred seventy Sprague Dawley rats were grouped in 5 clusters randomly. Oral mucosal wounds were induced in all rats except for the control group. Phenytoin and guajava leaf extract were used as a mouthwash. Twelve rats from the 5 groups were euthanized on day 7th and 10th, and 10 rats from each group were sacrificed on the 14th day. Interleukin-6 and total antioxidant capacity were determined in the serum. The tissues were evaluated for pathological and stereological assessments. Phytochemical analyses were performed on the hydroalcoholic extract of Psidium guajava L to determine the antioxidant potency. RESULTS: Total phenolic content test and DPPH analysis demonstrated the high potential of antioxidant capacity of Psidium guajava L. Decreasing IL-6 and increasing TAC were seen in the guajava hydroalcoholic extract and phenytoin groups. The difference of IL-6 between the wound treated guajava group and the wounded group was significant. The wound treated guajava group and wound treated phenytoin group on the 14th day increased the number of fibroblast cells and volume density of sub-mucosae effectively to the same thickness to be considered as a healed sub-mucosae layer. The volume density of the epithelium changes showed statistically significant different responses based on gender. CONCLUSION: In conclusion, hydroalcoholic extract of Psidium guajava L leaves might exert theraputic effects on oral mucositis.

Anti-Inflammatory, Antioxidant, and Healing-Promoting Effects of Aloe vera Extract in the Experimental Colitis in Rats.

BACKGROUND: Ulcerative colitis is a worldwide chronic gastrointestinal disease characterized by variable extensions of colon mucosal inflammation. The available drugs have an incomplete response with various side effects and socioeconomic impacts. Aloe barbadensis Miller (Aloe vera) is a well-known medicinal plant with diverse pharmacological and therapeutic activities. As a result, in the current study, Aloe vera was selected to evaluate its therapeutic effects on experimental colitis in rats. METHODS: This study is intended to evaluate the possible beneficial effect of Aloe vera for the treatment of experimental colitis. Trinitrobenzenesulfonic acid (TNBS) was used to induce experimental colitis in 60 of 70 Wistar rats. The rats were grouped in 7 clusters including healthy control, negative, positive control (received sulfasalazine), and test groups treated with Aloe vera extracts via oral or rectal routes. Macroscopic and histologic factors as well as the biochemical parameters were evaluated on day 7. RESULTS: In the present study, it was found that serum levels of tumor necrosis factor-α (75 vs. 44 pg./ml), interleukin-6 (41 vs. 21 pg/ml), and nitric oxide (24 vs. 6 µm/ml) in TNBS-induced untreated colitis treatment were significantly increased as compared to healthy control. Similar patterns were also observed in malondialdehyde (76.41 vs. 236.35 µg/mg) and myeloperoxidase (4.24 vs. 29.38 U/mg) in colonic tissue. Among different treatments, rectal administration of Aloe vera extract (400 mg/kg) exhibited the best result in which serum concentration of tumor necrosis factor-α (55 pg/ml), interleukin-6 (24 pg/ml), and nitric oxide (10 µm/ml) and the levels of malondialdehyde (102.67 µg/mg), as well as myeloperoxidase (12.29 U/mg) in colon tissue, were reduced as compared to the untreated group. Also, the body weight and colon weight/length ratios were more improved in the treated group with 400 mg/kg Aloe vera extract, rectally. CONCLUSION: Aloe vera extract exhibited a therapeutic effect in TNBS-induced colitis, and local, rectal administration of Aloe vera extract was more effective than oral administration.

Novel strategy of cartilage repairing via application of P. atlantica with stem cells and collagen.

Osteoarthritis (OA) is an inflammatory joint condition, still lacking effective treatments. Some factors consider as the main causes of OA, including biochemical, mechanical, and genetic factors. The growth of studies confirmed that modern medicine in combination with folk medicine regarding the arrival of reliable, efficient, and safe therapeutic products against OA. In the present study, the effects of various single and combinatorial treatments of knee articular cartilage, including stem cells, collagen, and P. atlantica hydroalcoholic leaves extract were investigated in a rat-induced OA model. On week 12 after OA confirmation, histopathology and radiography assessments were evaluated and the serum and synovial fluid levels of TAC, TNF-α, PEG2, MPO, MMP3, MMP13, and MDA were also measured. Combination therapy of OA-induced rats with hydroalcoholic extract of P. atlantic leaves, stem cells, and collagen considerably increased the efficacy of treatment as evidenced by increasing the TAC and lowering TNF-α, MPO, MMP3, and MMP13 compared to control group and even groups received single therapy. This is in agreement with a high amount of total phenolic compounds and antioxidant capacities of the hydroalcoholic extract of P. atlantic leaves. It is concluded that multifunctional agents targeting the pathophysiology of OA has exhibited significant therapeutic effects against OA.

The Antioxidant and Anti-Inflammatory Effects of Quercus brantii Extract on TNBS-Induced Ulcerative Colitis in Rats.

OBJECTIVES: Ulcerative colitis is a common subtype of persistent inflammatory bowel disease with high morbidity consequences. Despite unknown definite pathogenesis, multiple anti-inflammatory medications are used for its treatment. Traditionally, Quercus brantii (QB), mostly available in the Middle East, has been used for gastrointestinal disorders. Other beneficial effects associated with QB include reduction of oxidative stress, inflammations, homeostatic instability, and improvement in clinical conditions. MATERIALS AND METHODS: This experimental study was designed to assess the possible therapeutic effects of QB on UC and compare its effects with those of sulfasalazine. Of the 70 Wistar rats clustered in seven groups, ten received only alcohols and sixty were confirmed to be suffering from trinitrobenzene sulfonic acid- (TNBS-) induced colitis. Four groups received different dosages of QB extract via oral and rectal routes, one received sulfasalazine, and the other remaining two groups received nothing. The effects of QB were evaluated by assessing macroscopic and histologic scoring, measuring inflammatory mediators, and determining oxidative stress markers. RESULTS: Comparing to the untreated TNBS-induced control groups, QB-treated groups showed a dose- and route-dependent improvement comparable with sulfasalazine. Treating rats with QB reduced the microscopic and macroscopic damage, decreased TNF-α, IL-6, NO, MPO activity, and MDA content, increased superoxide dismutase (SOD) activity, and reduced body weight loss. CONCLUSIONS: Our data recommended the anti-inflammatory and antioxidant effects of QB extract in a dose-dependent manner.

Core-shell chitosan/PVA-based nanofibrous scaffolds loaded with Satureja mutica or Oliveria decumbens essential oils as enhanced antimicrobial wound dressing.

Wounds are prone to bacterial infections, which cause a delayed healing process. Regarding the emergence of bacterial resistance to common antibiotics, using natural antimicrobial agents can be beneficial. Chitosan is a biological polymer, which has shown partial antioxidant and antimicrobial activities. In this study, core-shell nanofibrous scaffolds composed of chitosan (CS)/polyvinyl alcohol (PVA) as the core and polyvinylpyrrolidone (PVP)/ maltodextrin (MD) as the shell were developed. Satureja mutica (S. mutica) or Oliveria decumbens (O. decumbens) essential oil (EO) was encapsulated into the core of the produced scaffolds. The broth microdilution analysis showed significant antimicrobial activity of the EOs. The SEM analysis indicated that the unloaded and loaded core-shell scaffolds with S. mutica or O. decumbens EO had a uniform, beadless structure with fiber mean diameters of 210 ± 50, 250 ± 45, and 225 ± 46 nm, respectively. The CS/PVA-PVP/MD and CS/PVA/EO-PVP/MD scaffolds indicated suitable mechanical properties. The addition of the studied EOs enhanced the antioxidant activity of the scaffolds. The antimicrobial test of produced scaffolds showed that loading of 10% S. mutica or O. decumbens EO could broaden the microbicidal activity of the CS/PVA-PVP/MD scaffolds. These results revealed that the CS/PVA/EO-PVP/MD nanofibrous scaffolds are promising candidates for wound dressing.

Effect of flaxseed oil on biochemical parameters, hormonal indexes and stereological changes in ovariectomized rats.

The ovariectomized rat is a widely used preclinical model for studying postmenopausal and its complications. In this study, the therapeutic effect of flaxseed oil on the ovariectomized adult rats was investigated. Our results showed that biochemical parameters including calcium, oestrogen and progesterone levels increase 8 weeks after ovariectomy in rats. Also, the amount of alkaline phosphatase decreased significantly after 8 weeks compared with the OVX rat. The healing potential of flaxseed oil was proven by successfully recovering the affected tissue and preventing the unpleasant symptoms of ovariectomized rats. The biological effects of flaxseed oil may be due to high amounts of fatty acids, phytoestrogens and an array of antioxidants. The results suggest that flaxseed oil can mimic the action of oestrogen and can be a potential treatment for hormone replacement therapy (HRT).

Effects of Calendula Officinalis and Hypericum Perforatum on Antioxidant, Anti-Inflammatory, and Histopathology Indices of Induced Periodontitis in Male Rats.

STATEMENT OF THE PROBLEM: Periodontitis is one of the most common bacterial infections of the oral cavity. It is important to find adjunctive methods for chemical treatment of periodontitis with less complications and proven therapeutic properties. PURPOSE: The aim of this study was to compare the effects of Calendula officinalis and Hypericum perforatum on antioxidant, anti-inflammatory and histopathologic indices of induced periodontitis in male rats. MATERIALS AND METHOD: In this experimental animal study, forty adult male Sprague-Dawley rats were randomly divided into 4 groups (n=10) and then experimental periodontitis was induced by 3-0 nylon non-absorbable ligature. Each group was treated for 10 days as follows: 1) H. perforatum hydroalcoholic extract, 1000 mg/kg/daily, orally; 2) C. officinalis hydroalcoholic extract, 1000 mg/kg/daily, orally; 3) a mix of the two plants, 1000 mg/kg/ daily, orally, 4) normal saline solution. At the end of study, blood sample were obtained via cardiocentesis, the rats were euthanized, and their maxillae were removed. The samples were analyzed for histopathological scores and total antioxidant capacity and IL-1ß were measured. RESULTS: Mixed hydroalchoholic extract of H. perforatum and C. officinalis decreased IL-1ß (4.3020±0.63), and increased the antioxidant parameter in comparison to the control group (3.1192±0.43) (p< 0.001). There were significant histopathological differences between the treatment groups and the control group. CONCLUSION: Mixed hydroalchoholic extract of H. perforatum and C. officinalis might be considered as an adjunctive treatment for periodontitis.

The Therapeutic Effect of Shark Liver Oil in a Rat Model of Acetic Acid-Induced Ulcerative Colitis.

Ulcerative colitis (UC) is one of the most well-known types of inflammatory bowel disease that manifests as recurrent inflammation of rectum and colon. The goal of this study is to evaluate the protective effects of shark liver oil (SLO) on acetic acid-induced ulcerative colitis in rats. Eighty induced UC rats were randomly divided into ten equal groups and received the following treatments for seven days: 1 ml of normal saline rectally, 1 ml of gel base (carboxymethyl cellulose) rectally, 10 mg/kg of Asacol rectally, 10 mg/kg of mesalazine orally, 5% gel form of SLO rectally, 10% gel form of SLO rectally, 200 mg of SLO orally, and 400 mg of SLO orally. We examined the oxidative stress indices, histopathological features, and body weight changes, as well as the function of the liver and kidneys at the end of treatment. Administration of 10% rectal and 400 mg oral SLO resulted in a significant weight gain. Also, glutathione peroxidase activity was significantly higher in 5% and 10% SLO-treated groups, and elevated superoxide dismutase activity in rats that received 5% SLO was observed compared to negative control and Asacol groups. While no significant changes were observed in most of the kidney and liver function markers, higher levels of aspartate aminotransferase were detected in the group that received 400 mg SLO orally compared to negative control and Asacol groups. Many histopathological signs of improvement were observed in mesalazine, Asacol, and SLO groups. There were no significant changes detected in the mean rank among different groups. Our data indicate that SLO supplementation could improve the amelioration of acetic acid-induced UC in rats due to its antioxidant effects.

Preventive Effects of Intrauterine Injection of Bone Marrow-Derived Mesenchymal Stromal Cell-Conditioned Media on Uterine Fibrosis Immediately after Endometrial Curettage in Rabbit.

Uterine fibrosis is an acquired disorder leading to menstrual irregularities, implantation impairment, and abortion. Mesenchymal stromal cells (MSCs) have antifibrotic properties through chemokine secretion. MSC-conditioned media (MSC-CM) contain paracrine components-exosomes-with a great potential for repairing damaged tissue or preventing fibrosis. The main goal of this study was to evaluate the preventive effects of bone marrow-derived MSC-CM (BM-MSC-CM) on uterine fibrosis after uterine curettage in rabbits. This study included 12 female rabbits (24 uterine horns in total). Excised uteri of each of the 12 female rabbits were randomly divided into four groups of intact negative control, curettage positive control, BM-MSC injection, and BM-MSC-CM injection in the way that two corresponding uteri from a rabbit were allocated to different groups. The MSC-CM were collected from cultivated BM-MSCs 48 hours after having been washed three times and replaced in serum-free media. Through a surgical approach, the caudal parts of the uteri were submitted to traumatic endometrial curettage, except for the intact negative uteri. After suturing the uterine walls, BM-MSCs or BM-MSC-CM were injected in the curettage site. Endometrial regeneration was histologically evaluated 30 days after treatment. Based on the evaluation of histomorphometric indices, curettage with or without preventive injections increased the growth of endometrial layers. However, the amount of fibrotic tissue in the CM and the BM-MSC injection groups was the same as the normal control groups, and all were less than the curettage group. A single injection of CM of MSCs after 30 days prevented the fibrotic tissue formation induced by curettage in endometrial layers of rabbits. Injecting BM-MSC-CM immediately after curettage prevented and reduced the uterine fibrosis similar to BM-MSCs in a rabbit model.