Curcumin Effect on the Prevention of Gingival Overgrowth Following Phenytoin Consumption in Rats: A Clinicohistological and Immunohistochemical Study.

AIM: At the moment there is no clear evidence with clinico-histological and immunohistochemical studies in animals to show the curcumin effect on the gingival overgrowth following phenytoin consumption. The purpose of the present study was to identify this subject. MATERIALS AND METHODS: In this experimental study, 50 adult male Wistar rats were divided into three groups. The rats in groups I and II received 100 mg/kg of phenytoin per day. Group II also received 20 mg/kg intraperitoneal curcumin per day. The control group received the curcumin vehicle only. Gingival clinical dimensions were measured at the beginning and end of the study. The rats were then sacrificed, biopsy of gingiva was prepared, and the samples were stained with hematoxylin-eosin. Morphometry was performed to evaluate the degree of inflammation, epithelial thickness, number, and cross-sectional area of the blood vessels. Immunohistochemical staining was performed using Ki67 and α-SMA. RESULTS: Compared to the control group, Phenytoin in group I increased gingival volume. There was significance difference in group II with group I and control after intervention in the clinical view (p = 0.002). The difference in the number of blood vessels between groups I and II was statistically significant (p = 0.001). Significant differences were observed in blood vessel cross-sectional area (p = 0.001), epithelial thickness (p = 0.002), Ki67, and α-SMA expression between groups I and II (p = 0.001). CONCLUSION: In rats, curcumin seems to exerts its effects in preventing an increase in gingival volume caused by Phenytoin through decreasing the inflammatory infiltration, decreasing the number of blood vessels and increasing their cross-sectional area, decreasing the thickness of the epithelium, and decreasing the expression of Ki67 and α-SMA. CLINICAL SIGNIFICANCE: It is suggested that curcumin may be effective in treatment of gingival enlargement following Phenytoin consumption in future. Larger sample size and clinical trials study are recommended. How to cite this article: Eftekharian S, Seifi S, Satari FD, et al. Curcumin Effect on the Prevention of Gingival Overgrowth Following Phenytoin Consumption in Rats: A Clinicohistological and Immunohistochemical Study. J Contemp Dent Pract 2019;20(10):1146-1150.

Comparison of Placenta PCR and Maternal Serology of Aborted Women for Detection of Toxoplasma gondii in Ardabil, Iran.

Primary maternal infection with toxoplasmosis during pregnancy is frequently associated with transplacental transmission of the parasite to the fetus. This study was conducted to test the utility of PCR assay to detect recent infections with Toxoplasma in aborted women at various gestational ages who referred to Obstetrics and Gynecology Department of Alavi Hospital in Ardabil during 2014 and 2016. Two hundred women with a history of single or repeated abortion were investigated in this study. Blood samples were tested for specific anti-Toxoplasma IgM and IgG antibodies by ELISA. According to the results, 53.5% of the women under study were positive for anti-Toxoplasma antibodies: 4.0% of them had IgM, 43.0% had IgG, and 6.5% had both IgM and IgG. Subsequently, Nested-PCR analysis was used to detect T. gondii DNA in the placenta of subjects. In 10.5% of the women, the results were positive for 529 bp element of T. gondii. Among them, 5 (23.8%) cases were IgM positive, 1 (4.8%) case was IgG positive, and 11 (52.4%) were both IgM and IgG positive. In 4 (19.0%) patients, none of the antibodies were found to be positive. In total, 16 patients had positive results in both ELISA and PCR methods, and 174 cases had negative results for new infection. The findings of this study revealed that T. gondii might be one of the significant factors leading to abortion, and that the analysis of placenta can be important in order to achieve increased detection sensitivity.

Relevance of Helicobacter pylori vacA 3'-end Region Polymorphism to Gastric Cancer.

BACKGROUND: Helicobacter pylori vacA genotypes play an important role in the pathogenesis of severe gastrointestinal disease. MATERIALS AND METHODS: We identified a novel polymorphic site in the 3'-end region of H. pylori vacA gene, denoted by c1/-c2 (c1: with deletion of 15 bp), and examined associations of this and the previous four sites as well as cagA status with gastroduodenal diseases, in a total of 217 Iranian H. pylori isolates. Histopathologic evaluations were performed and patients with gastric cancer (GC) were further classified based on the anatomic site of tumor, including cardia and noncardia GC, and the histopathologic type of tumor, including intestinal- and diffuse-type GC. RESULTS: The vacA m1, i1, d1, c1, and cagA genotypes were significantly associated with an increased risk of GC, the odds ratio (95% confidence interval) was 4.29 (2.03-9.08), 6.11 (2.63-14.19), 3.18 (1.49-6.76), 15.13 (5.86-39.01), and 2.59 (1.09-6.12), respectively. The vacA c1 genotype had an increased age- and sex-adjusted risk for GC by the multiple logistic regression analysis; the OR was 38.32 (95% CI, 6.60-222.29). This association was independent of and larger than the associations of the m-, i-, and d-type of vacA or cagA status with GC. No significant correlation was found between s1, whether independently or in combination, and the risk of GC or peptic ulcer disease (PUD). The vacA i1 and cagA genotypes were linked to an increased risk of PUD; the OR (95% CI) was 2.80 (1.45-5.40) and 2.62 (1.23-5.61), respectively. The presence of both the vacA i1 and cagA genotypes further increased the risk of PUD; the OR was 5.20 (95% CI, 1.92-14.03). CONCLUSION: The H. pylori vacA c1 genotype might therefore be one of the strongest risk predictors of GC in male patients aged ≥55 in Iran.

The effect of the glycolipoprotein extract (G-90) from earthworm Eisenia foetida on the wound healing process in alloxan-induced diabetic rats.

Diabetes is now regarded as a major public health problem. The number of patients is estimated to increase to over 439 million cases by 2030. One of the major health clinical problems in patients with diabetes patients is impaired wound healing. Diabetic foot ulcer is a major complication of diabetes mellitus in 12 to 25% of patients, which increases the risk of damage in the limbs or amputation. The earthworm Eisenia foetida glycolipoprotein (as known G-90) is a blend of macromolecules with some biological properties including mitogenicity, anticoagulation, fibrinolysis, bacteriostatic and antioxidatiaon. Given the biological properties of G-90, this study was conducted to investigate the effect of extract obtained from the homogenate of Eisenia foetida (G-90) on the wound healing process in alloxan-induced diabetic rats. The results of the present study revealed that treatment by using G-90 can speed up the wound healing process, which is exactly similar to the effect of D-panthenol treatment in rats. These findings also demonstrated that G-90 treatment decreases the risk of infection in the wound site compared with D-panthenol treatment. In addition, histological analysis indicated that a better extracellular matrix formation with increased fibroblast proliferation, neovascularization, collagen synthesis and early epithelial layer formation was observed in G-90 treated group. Therefore, the G-90 could be considered as a new wound healing agent introducing promising therapeutic approaches in both human and veterinary medicine. Copyright © 2016 John Wiley & Sons, Ltd.

Poly(vinyl alcohol) /Alginate nanofibrous mats containing Malva Sylvestris extract: Synthesis, characterization, in vitro and in vivo assessments for burn wound applications.

An important part of wound healing is providing effective wound care, coupled with preventing wound infection, which slows or disrupts healing. There are currently many herbal plants that have historical supernatural properties that show remarkable wound healing abilities. These herbal extracts have shown promising results when applied to electrospun nanofibrous mats platforms for wound healing. Accordingly, Malva Sylvestris extract (MS) was electrospun into polyvinyl alcohol/alginate nanofibrous mats (PVA/ALG). Field Emission Scanning Electron Microscopy (FESEM) demonstrated that the fiber diameter ranged from approximately 100-200 nm in nanofibrous mats, with a uniform appearance without beads. MS extract was detected in nanofibrous mats by Fourier Transform Infrared Spectroscopy (FTIR). A major benefit of incorporating MS extract into PVA/ALG nanofibrous mats is that their alterations have resulted in enhanced mechanical characteristics. The nanofibrous mats containing MS extracts showed significantly increased antibacterial efficacy against Gram-positive and Gram-negative bacteria. Based on the findings from in vivo experiments, the PVA/ALG/MS1 (M2) dressing demonstrated a wound closure rate of 93-94 % within 21 days of treatment in rats, indicating its significant potential for use as a wound dressing agent in the treatment of burn injuries. The combination of PVA, ALG, and MS1 in this nanofibrous mats exhibited beneficial properties, including biocompatibility, suitable mechanical strength, and the ability to promote cellular proliferation and angiogenesis, further validating its effectiveness as a wound healing dressing.

Catecholamines polymerization crosslinking for alginate-based burn wound dressings developed with ciprofloxacin and zinc oxide interactions.

There is an increasing demand for stable and durable wound dressings to treat burn injuries and infections. Bioactive electrospun nanofibrous mats with antibacterial properties are promising for wound dressing usage. Electrospinning of biopolymers for wound dressing applications needs post-spinning crosslinking to prevent mat dissolution in moist wound environments. Here, we prepared durable wound dressing by using the Dopamine (DA) polymerization crosslinking in Alginate (ALG)/Polyvinyl alcohol (PVA) nanofibrous mats, which are developed by Ciprofloxacin (CIP) and Zinc oxide (ZO). The nanofibrous mats were investigated by FESEM, FTIR, mechanical strength, water contact angle, degradation, degree of swelling, and WVTR tests. The analyses demonstrate the nanofibrous mats with uniform and unbranched fibers, with a hydrophilic nature, which was porous, durable, and stable. Also, it showed the CIP and ZO addition enhanced their durability by crosslinking reinforcement. In addition, the drug release and antibacterial assays demonstrated the pH-sensitive release with more drug release at higher pH (bacterial invasion) and impressive antibacterial activity (up to 99 %). In the burn wound model in rats, the ALG/PVA/DA/CIP/ZO nanofibrous mats displayed excellent wound healing ability in wound closure and tissue regeneration. Also, complete re-epithelization and remodeling and highest collagen synthesis in histological assessment.

Bioactive nanofibrous mats constructs: Separate efficacy of Lawsonia inermis and Scrophularia striata extracts in PVA/alginate matrices for enhanced wound healing.

The study explores the use of electrospinning technology to create advanced wound dressing materials by integrating natural extracts from Lawsonia inermis (LI) and Scrophularia striata (SS) into nanofibrous matrices composed of Polyvinyl Alcohol (PVA) and Alginate (ALG). These macromolecular complexes aim to leverage the unique properties of the botanical extracts for wound healing purposes. The research assesses the physical, chemical, and mechanical attributes of the nanofibrous constructs as well as their antimicrobial activities and ability to promote wound repair. Evaluation of Cellular Viability and Cytotoxicity (MTT) tests showed high biocompatibility of the nanofibrous mats, with cell viability percentages of 92 % for LI-loaded mats and 89 % for SS-loaded mats. The antibacterial rate of extract-containing mats was 70 % higher than non-extract-containing mats. In vivo assessments on rat models with burn injuries demonstrated that mats containing LI and SS extracts substantially accelerate tissue regeneration and overall healing. Nanofibrous mats containing LI extract showed a 45 % faster wound healing process than the control, while those containing SS extract showed a 40 % improvement. Overall, the study highlights the potential of PVA/ALG nanofibrous mats augmented with LI and SS extracts as effective platforms for wound management, offering enhanced properties for superior healing outcomes.

Aortic Injury Induced by Benzo(a)pyrene and Atherogenic Diet Increased Hepatic FGF21 Expression in C57BL/6J Mice.

Background: Benzo(a)pyrene (BaP), an environmental toxicant and endocrine disruptor, has been shown to exacerbate atherosclerosis when combined with a high-fat diet. Fibroblast Growth Factor-21 (FGF21), a novel hormone with anti-atherosclerotic properties, is associated with the presence of atherosclerosis and reduces plaque formation in experimental animals. Objectives: The present study aimed to investigate the chronic effect of BaP injection on hepatic FGF21 expression, as an anti-atherosclerotic hormone, in mice fed with or without an atherogenic diet (AtD). Methods: Eighteen C57BL/6J male mice (6 weeks) were randomly divided into six groups based on the dosage and diet. Blood samples were collected, and serum cholesterol, triglyceride, HDL-C, LDL-C, and glucose levels were measured. FGF21 expression was assessed by quantitative real-time PCR. Atherosclerotic lesions in mice were studied with Oil Red O (ORO) staining. Results: Benzo(a)pyrene causes a significant increase in liver FGF21 expression in a dose-dependent manner, and BaP co-exposure with AtD leads to a further increase in FGF21 expression. Additionally, the addition of BaP to AtD significantly increased the serum glucose, cholesterol, and LDL-C levels and accelerated the formation of atherosclerotic lesions. Besides, our findings showed that there is a significant positive correlation between FGF21 expression and glucose, cholesterol, LDL-C, and ORO-positive areas. Conclusions: Our findings revealed that BaP increases the expression of endogenous FGF21 in treated animals as a compensatory response to protect the heart from atherosclerosis induced by BaP and AtD.

Histomorphometric comparative study of blood vessels and their pattern in follicular cyst, odontogenic keratocyst, and ameloblastoma.

OBJECTIVE: The present study aimed at assessment and histomorphometric analysis of intratumoral and peritumoral (cystic) blood vessels in odontogenic lesions and their pattern on their clinical behavior by immunohistochemistry and morphometry. METHODS: In a descriptive and analytical cross-sectional study, 45 paraffin blocks of ameloblastoma, odontogenic keratocyst, and follicular cyst were selected and stained immunohistochemically for CD34. In each slide, images of 3 microscopic fields with the highest microvessel density in intratumoral and peritumoral (cystic) areas were captured at 40× magnification with attached camera system. Inner vascular diameter (IVD) and outer vascular diameter (OVD), cross-sectional area (CSA), and the wall thickness (WT) of the vessels were measured with Motic Plus 2 software. The vascular pattern in odontogenic lesions was analyzed. RESULTS: Outer vascular diameter, IVD, and CSA of the vessels in peritumoral (cystic) areas were greater in ameloblastoma than keratocyst (P = 0.001) and follicular cyst (P < 0.001). However, WT of the blood vessels did not show any significant statistical difference among the 3 odontogenic lesions (P = 0.05). The differences in OVD, IVD (P = 0.8), CSA (P = 0.6), and WT (P = 0.4) of the blood vessels in intratumoral (cystic) areas were not statistically significant. The blood vessel pattern was circumferential in ameloblastoma, and it was directional in keratocyst and follicular cyst. CONCLUSIONS: Morphometric specifications of blood vessels (IVD, OVD, CSA) and their pattern in peritumoral (cystic) areas may influence the aggressive clinical behavior of ameloblastoma in comparison with keratocyst and follicular cyst.

Wound Healing: An Overview of Wound Dressings on Health Care.

Chronic wound healing is a time-consuming and complicated process. Severe risk for wound healing that can be life-threatening is bacterial invasion and wound during the healing process. Therefore, it is necessary to use a sui barrier to create a controlled environment for wound healing. Various wound dressings such as hydrocolloids, hydrogels, sponges, foams, films, and micro and nanofibers have been explored in recent decades. High surface-to-volume ratio, high similarity to the biological structure of the extracellular matrix, high porosity and very small pore size are some advantages of nanofibers that have become potential candidates for wound healing applications. Different methods are used to fabricate nanofibers like drawing-processing, template synthesis, self-assembly, phase separation, force-spinning and electrospinning. Electrospinning is the most desirable method due to the possibility of producing independent, accessible and controllable nanofibers. The fiberbased wound dressings and their manufacturing methods have been extensively discussed.

N-Acetylcysteine attenuated pulmonary fibrosis induced by bleomycin via immunomodulation responses.

Background and purpose: Pulmonary fibrosis (PF) is a chronic and life-threatening interstitial lung disease. N-acetyl cysteine (NAC) is an antioxidant pharmaceutically available to reduce endothelial dysfunction, inflammation, and fibrosis, however, the therapeutic effect of NAC on PF has not been clearly identified. This research aimed to investigate the possible therapeutic impact of NAC on PF induced by bleomycin in the rat model. Experimental approach: Rats received intraperitoneal injections of NAC at 150, 300, and 600 mg/kg for 28 days before bleomycin, while the positive and negative control groups were treated with bleomycin alone and normal saline, respectively. Then, rats' lung tissues were isolated and leukocyte infiltration and also collagen deposition were evaluated using hematoxylin and eosin and Mallory trichrome stainings, respectively. In addition, the levels of IL-17, and TGF-ß cytokines in bronchoalveolar lavage fluid and hydroxyproline in homogenized lung tissues were assayed using the ELISA method. Findings/Results: Histological findings indicated that NAC decreased leukocyte infiltration, collagen deposition, and fibrosis score in the bleomycin-induced PF tissue. Moreover, NAC significantly reduced TGF-ß and hydroxyproline levels at 300-600 mg/kg, as well as IL-17 cytokine at 600 mg/kg. Conclusion and implications: NAC showed a potential anti-fibrotic effect by reducing hydroxyproline and TGF-ß as well as an anti-inflammatory effect by decreasing IL-17 cytokine. So, it may be administered as a prophylactic or therapeutic candidate agent to attenuate PF via immunomodulatory effects. Although, future studies are suggested.

Comparison of the apical seal obtained by Adseal, Proseal, and AH26 sealers in root canal obturation with lateral compaction technique.

Background: Root canal obturation is an important step in endodontic treatment, which is performed aiming to three-dimensionally seal the canal and prevent microleakage, reentry, and proliferation of microorganisms in the root canal system. On the other hand, microleakage eventually leads to root canal treatment failure. Sealing ability is an important property of endodontic sealers. This in vitro study aimed to compare the quality of apical seals obtained by three endodontic sealers. Materials and Methods: This in vitro experimental study evaluated 48 extracted single-canal maxillary incisors. Hard- and soft-tissue residues were removed and the teeth were immersed in 5.25% of sodium hypochlorite for disinfection. The teeth were decoronated at the cementoenamel junction with a diamond disc such that 10 mm of root length remained. Canal patency was ensured using a #10 K-file. The canals were then instrumented with ProTaper rotary system. The canals were randomly divided into three experimental groups for the application of Adseal, Proseal, and AH26 sealers, and positive and negative control groups. Sealers were applied in the canals using lateral compaction technique. The external root surfaces were then coated with two layers of nail varnish except for the apical 3 mm. The amount of microleakage was quantified using the dye-penetration technique. The Tukey's test was used to compare the microleakage between the experimental and control groups. The Kruskal-Wallis test was applied to compare the microleakage of experimental groups (P < 0.05). Results: The amount of microleakage in canals filled with Adseal, Proseal, and AH26 sealers with lateral compaction technique was 2.33 ± 0.64, 2.2 ± 0.81, and 2.22 ± 0.71 µm, respectively. No significant difference was noted among the three sealers regarding microleakage (P = 0.84). However, the amount of microleakage in the sealer groups was significantly lower than that in the control group (P < 0.001). Conclusion: The application of Adseal, Proseal, and AH26 had equal efficacy for the provision of optimal apical seal in filling of root canals with lateral compaction technique. The application of sealers yielded a significantly superior apical seal compared with the control group.

Disulfiram ameliorates bleomycin induced pulmonary inflammation and fibrosis in rats.

Bleomycin (BL) is a widely used anticancer drug that can cause pulmonary fibrosis due to increased fibroblast proliferation and increased secretion of extracellular matrix. RASSF1A is a tumor suppressor gene that is down-regulated by DNA methylation during fibrosis. Disulfiram (DSF), a noncytosine DNA methyltransferase inhibitor, can revert epigenetic biomarkers and re-express silenced genes. We investigated anti-inflammatory and anti-fibrotic effects of DSF on regulation of epigenetic molecules and histopathology in a rat model of BL induced pulmonary fibrosis. We used six groups of rats: sesame oil (SO) control (Co) group, BL group, BL + SO group and three BL + DSF groups administered 1 mg/kg DSF (BL + DSF), 10 mg/kg DSF (BL + DSF10) or 100 mg/kg DSF (BL + DSF100), respectively. BL was administered intratracheally to induce pulmonary fibrosis. DSF and SO were injected intraperitoneally (i.p.) 2 days before BL administration; these injections were continued for 3 weeks. At the end of the study, lung tissues were removed for molecular and histopathologic studies. Administration of 10 or 100 mg/kg DSF after BL induced pulmonary inflammation and fibrosis, and up-regulated RASSF1A and down-regulated TNF-α and IL-1 ß compared to the BL and BL + SO groups. A RASSF1A unmethylated band was observed using the methylation-specific PCR technique in rats that had been administered 10 and 100 mg/kg DSF, which indicated partial DNA demethylation. Histopathologic evaluation revealed that fibrosis and all inflammatory scores were decreased significantly in the BL + DSF10 and BL + DSF100 groups compared to the BL group. Our findings indicate that DSF modified DNA methylation by up-regulating RASSF1A, which reduced inflammation and fibrosis in BL induced pulmonary inflammation and fibrosis.

The effect of nonylphenol exposure on the stimulation of melanomacrophage centers, estrogen and testosterone level, and ERα gene expression in goldfish.

The present study tried to measure the formation of melanomacrophage centers (MMCs) in various organs of male and female goldfish exposed to nonylphenol (NP) and aimed to assess its relationship with the main sexual hormones, estrogen receptor expression, and the pigment content of the MMCs. Immature goldfish were exposed to 10-6 and 10-7 M NP for 25 days. After obtaining blood for measuring testosterone and estrogen (E2) levels, tissue samples were collected from various organs for histological studies, quantifying pigments using ImageJ software and chemical analysis, and measuring ERα gene expression. Results showed that the order of forming MMCs in various organs exposed to NP was liver > spleen > kidney, and the order of ERα gene expression was liver > testes > spleen > kidney in the male, and liver > spleen > kidney > ovaries in the female. Among the three pigments present in MMCs after exposure to the two doses of NP, melanin was more obvious (especially in the liver) and increased mostly in a dose-dependent manner in both sexes (especially in the male). Chemical analyses confirmed these results. Measurement of testosterone and E2 level in male and female goldfish showed that NP had more effect on the concentration of these hormones in male fish, indicating more endocrine-disrupting potential of NP against the male fish. Generally, the increase of melanin content of melanomacrophage centers coincided with the increase of ERα gene expression and decrease of testosterone level in goldfish after exposure to NP.

Hypothyroidism and Fertility: An Animal Model follows up in The Second-Generation.

Objective: Hypothyroidism is known as the most common endocrine disorder. The prevalence of hypothyroidism in the female and male population is 2% and 0.2%, respectively. Maternal hypothyroidism is a defect in the thyroid hormones transition from the mother to the fetus. The present study was conducted to find whether maternal hypothyroidism affects the fertility of the second generation. Materials and Methods: In this experimental study, twelve adult female rats weighting 180-220 g were randomly divided into case and control groups. Hypothyroidism was induced by dissolving 0.1 g/L of 6-n-propyl-2-thiouracil in drinking water toward the end of pregnancy and lactation. At the end of the breastfeeding period, the blood samples of female children were collected. Six healthy, mature, female rats were selected and kept until they reached maturity, and were then mated with male rats. After observing the female rats' delivery, blood samples were collected from their male and female newborns and the healthy rats were selected. Results: There was a significant difference in the volume and size of ovarian as well as in the number of secondary follicles in comparison with the control group (P=0.025). However, there were no significant changes in the other parameters including the number of primary follicles, the number of Graafian follicles and sperm parameters. There was no significant decrease in the testicular volume and size, number of Leydig cells and seminiferous tubules diameter. Conclusion: Maternal hypothyroidism has no significant effects on testicular tissue function, and sperm parameters in the second generation, but can significantly reduce the rate of secondary follicles in the second generation female rats.

Synthesis of biocompatible nanocrystalline cellulose against folate receptors as a novel carrier for targeted delivery of doxorubicin.

We designed amine-functionalized nanocrystalline cellulose grafted folic acid/magnetic nanoparticles (AF-NCC/Fe3O4 NPs) against folate receptors for targeted delivery of doxorubicin (DOX). Toxicity is a major side effect of DOX, damaging vital organs such as the heart, kidney, and liver; for example, it causes dilated cardiomyopathy and hepatotoxicity. Accordingly, we aimed to reduce this adverse effect and increase the targeted delivery of DOX to the right point of cancer cells by using the unique features of cancer cells. The characterizations were approved in each step using Fourier transform infrared (FTIR), scanning electron microscope (SEM), X-ray diffraction (XRD), transmission electron microscopy (TEM), energy dispersive X-ray (EDX), zeta potential, and dynamic light scattering (DLS) analysis techniques. Encapsulation efficacy of AF-NCC/Fe3O4 NPs was 99.6%; drug release investigations showed excellent stability in physiological conditions (pH âˆ¼ 7.4) and a high release rate in the low pH condition of cancer environments (pH âˆ¼ 5.0). The hemolysis assay and Masson's trichrome and hematoxylin and eosin (H&E) staining results showed that the nanocarrier was entirely biocompatible. In vitro cell viability study approved that the designed nanocarrier increased the therapeutic effects of DOX on Saos-2 cells. The cellular internalization results displayed a high percentage of uptake within 2 h. Real-time reverse transcriptase-polymerase chain reaction (RT-PCR) was applied for the evaluation of tumor protein p53 (p53), p21, and Bcl-2-associated X protein (Bax). DOX exerted its effects through DNA damage and oxidative stress that led to p53 upregulation, and p53 inhibited cell cycle progression. This arrest initiated apoptosis and inhibited cell migration. In summary, encapsulating DOX in AF-NCC/Fe3O4 NPs dramatically decreases the toxic effects of this chemotherapeutic agent on vital organs, especially on the heart. This smart nanocarrier increases the delivery of DOX using acid folic on its surface and also enhances the DOX release in the acidic environment of cancer cells. DOX exerts its therapeutic effects by the initiation of apoptosis and inhibition of migration.

Serotonin-1A receptor activation in the median raphe nucleus improves response learning-based strategy in 192IgG saporin-induced cognitive impairments.

Deficits in the translation between egocentric-allocentric strategies may become another diagnostic mark for neurodegenerative disorders, especially Alzheimer's disease. Regarding the specific regional distribution of serotonin-1A receptor in brain areas mediating allocentric (externally-centered) spatial navigation to the escape location, here we studied the effects of median raphe nucleus serotonin-1A autoreceptors stimulation, [8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT); 4 µg/0.5 µl saline], of a selective cholinergic denervation by intracerebroventricular administration of the 192IgG saporin (1µl/each ventricle), on male Wistar rats search strategies in a Morris maze during acquisition, and before probe sessions. Despite some evidence of spatial hippocampal dependent knowledge to those PBS/Saline animals, their performance dropped to chance levels on probe trial. Therefore, we considered two probabilities and first analyzed the ability of the rats to make better use of one or more strategies. We showed statistically significant increases in the distances associated with egocentric (body-centered) non-spatial strategies, random searching in particular, in 192IgG/8OH rats, which led to their improved performance. Second, considering to what extent a shift in search strategy use improves performance indicated that 8-OH-DPAT alone did not affect learning since it appeared the related performance was impaired over days. However, the strategy choices made by 192IgG/8OH rats increased performance by more than 12% compared to 192IgG/Saline rats, an effect reversed with pre-treatment by serotonin-1A receptor antagonist, N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl) cyclohexane-carboxamide (WAY 100635). The results strongly suggest the potential role of serotonergic system, via the serotonin-1A receptors, in spatial navigation. We argue that the receptors are of interest as therapeutic targets that can be used against age-related cognitive decline.

Effect of Cassia fistula L. aqueous extract in maternal reproductive outcome, some serum indices and fetal anomaly frequency in rat.

Background: Cassia fistula was used traditionally as laxative in pregnant women. Nevertheless, its fetal and maternal effects in pregnancy have not been studied yet. Methods: Oral (Lethal Dose, 50%) LD50 was determined in mice. In addition, a control group, pregnant rats in other 5 experimental groups (n=12) received orally C. fistula aqueous extract (500, 1000 and 2000 mg/kg), tween80 (10%) and distilled water during pregnancy up to the delivery (21-23 days). Some serum indices were evaluated in maternal blood samples after delivery. Histopathologic and histomorphometric evaluations were performed on the selected slices of newborn rats. Results: Anthraquinone content of the aqueous extract was 0.34% w/w. Oral LD50 was obtained more than 5000mg/kg. No abortions and newborn anomalies were observed in groups. The height and weight of the offspring were significantly reduced by the administration of 500, and 2000 mg/kg of extract compared to control. There was no significant change in maternal blood urea and creatinine. Higher concentration (2000mg/kg) led to ALT elevation. ALS levels decreased dose-dependency in treatment groups comparing to control. Histopathological findings showed significant lung vascular congestion, and hypertrophy of heart in group tween80, and significant hepatic parenchymal inflammation in tween80 and 2000mg/kg and 1000mg/kg groups. In all tissues of all groups, malpighian body area and bowman's capsule space significantly increased compared to the control group. Conclusion: It seems C. fistula extract is safe in pregnancy. Because of confounding role of tween80 in histopathological finding, more research is necessary.

Prenatal and breastfeeding exposure to low dose of diethylhexyl phthalate induces behavioral deficits and exacerbates oxidative stress in rat hippocampus.

Diethylhexyl phthalate (DEHP) is one of the most important derivatives of phthalate that has devastating effects on nervous system function. In this study, the effects of exposure with low doses of DEHP during pregnancy and lactation periods have been evaluated in rat's puppies. DEHP at doses 5, 40, 400 µg/kg/day and 300 mg/kg/day was given to mothers by gavage during pregnancy and lactation. The spatial and working memories were evaluated by Morris water maze test and Y maze, respectively. Oxidative stress levels were measured by biochemical tests. Histopathology of hippocampal tissue was assessed using hematoxylin and eosin, Nissl staining, and immunohistofluorescence in 60-days-old puppies. Behavioral data showed that low doses of DEHP decreased the working and spatial memories of male rats. Increased oxidative stress and decreased antioxidant activity were also observed in the hippocampus of rats which received the low doses of DEHP. However, neuronal damage, inflammation, and astrocyte activation were not significantly increased in the hippocampus of rats. Overall, exposure of mothers to low doses of DEHP during pregnancy and lactation cause behavioral deficits, especially in male newborn. The destructive effects of low doses of DEHP might be mediated through increased levels of oxidative stress in the brain.

Acute administration of sulfur-doped g-C3N4 induces cognitive deficits and exacerbates the levels of glial activation in mouse hippocampus.

During the last decades, graphitic carbon nitride (g-C3N4) has attracted increasing attention in several biomedical fields. In this study, the effects of sulfur-doped g-C3N4 (TCN) on cognitive function and histopathology of hippocampus were investigated in mice. The characteristics of synthetized sample were evaluated by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), Raman spectroscopy, transmission electron microscopy (TEM), field emission scanning electron microscopy (FESEM), and energy dispersive X-ray (EDX). Twenty-four male NMRI mice received vehicle, TCN at doses of 50, 150, or 500 mg/kg via gavage for one week. Morris water maze test was done to assess the cognitive function at day 14 post TCN administration. Nissl staining was used to determine the number of dark cells in the hippocampus. Immunostaining against NeuN, GFAP, and Iba1 was done to evaluate the neuronal density and levels of glial activation, respectively. Behavioral tests indicated that TCN reduces the spatial learning and memory in a dose-dependent manner. Histological evaluations showed an increased level of neuronal loss and glial activation in the hippocampus of TCN treated mice at doses of 150 and 500 mg/kg. Overall, our data indicate that TCN induces the cognitive impairment that is partly mediated via its exacerbating impacts on neuronal loss and glial activation.