The Effect of Dextrose Hypotonic vs Saline Hydration on Methotrexate-Induced Nephrotoxicity in Male and Female Rats.

Background: High-dose methotrexate (HDMTX) as a cytotoxic agent might cause various side effects. Hyperhydration has been implemented as the major strategy to decrease the potential risk of toxicities induced by HDMTX. This study aims to assess the renoprotective effect of hydration with dextrose water (DW) 5% versus normal saline (N/S) 0.9% against methotrexate (MTX) induced nephrotoxicity. Materials and Methods: This experimental animal study has been conducted on 36 Wistar rats (200-250 g) categorized into six groups, including male (n = 6) and female (n = 6) rats receiving sodium chloride 0.9% saline plus MTX, DW 5% plus MTX, or MTX alone. By the fifth day after the MTX injection, biochemical indexes were measured. The rats were also sacrificed and renal specimens were evaluated microscopically to determine kidney tissue damage (KTD). Results: The groups were not significantly different with regard to blood urea nitrogen (BUN) (P = 0.5), creatinine (Cr) (P = 0.24), kidney weight (P = 0.34), and urine flow (UF) (P = 0.5), while KTD score was remarkably less in the hydrated groups (P < 0.001). Weight loss in DW-treated rats was significantly more than N/S-treated ones, and creatinine clearance (CrCl) and urine load (UL) of Cr were statistically similar between males and females in the control group, but significantly lower among the DW5% treated males. Conclusion: Based on the findings of this study, hydration with N/S was superior to DW5% for the prevention from HDMTX-induced nephrotoxicity. Besides, we found insignificant differences between male versus female rats in response to the hydration for HDMTX-induced renoprotection; however, females probably benefit more.

Hard tissue formation in pulpotomized primary teeth in dogs with nanomaterials MCM-48 and MCM-48/hydroxyapatite: an in vivo animal study.

BACKGROUND: This animal study sought to evaluate two novel nanomaterials for pulpotomy of primary teeth and assess the short-term pulpal response and hard tissue formation in dogs. The results were compared with mineral trioxide aggregate (MTA). METHODS: This in vivo animal study on dogs evaluated 48 primary premolar teeth of 4 mongrel female dogs the age of 6-8 weeks, randomly divided into four groups (n = 12). The teeth underwent complete pulpotomy under general anesthesia. The pulp tissue was capped with MCM-48, MCM-48/Hydroxyapatite (HA), MTA (positive control), and gutta-percha (negative control), and the teeth were restored with intermediate restorative material (IRM) paste and amalgam. After 4-6 weeks, the teeth were extracted and histologically analyzed to assess the pulpal response to the pulpotomy agent. RESULTS: The data were analyzed using the Kruskal‒Wallis, Fisher's exact, Spearman's, and Mann‒Whitney tests. The four groups were not significantly different regarding the severity of inflammation (P = 0.53), extent of inflammation (P = 0.72), necrosis (P = 0.361), severity of edema (P = 0.52), extent of edema (P = 0.06), or connective tissue formation (P = 0.064). A significant correlation was noted between the severity and extent of inflammation (r = 0.954, P < 0.001). The four groups were significantly different regarding the frequency of bone formation (P = 0.012), extent of connective tissue formation (P = 0.047), severity of congestion (P = 0.02), and extent of congestion (P = 0.01). No bone formation was noted in the gutta-percha group. The type of newly formed bone was not significantly different among the three experimental groups (P = 0.320). CONCLUSION: MCM-48 and MCM-48/HA are bioactive nanomaterials that may serve as alternatives for pulpotomy of primary teeth due to their ability to induce hard tissue formation. The MCM-48 and MCM-48/HA mesoporous silica nanomaterials have the potential to induce osteogenesis and tertiary (reparative) dentin formation.

Ameliorative Effect of Aqueous and Hydroalcoholic Extracts of Scrophularia striata Boiss. on Murine Model of Experimental Colitis.

Background: Scrophularia striata Boiss. (S. striata) is a flowering plant with several therapeutic properties including antiinflammatory, antioxidant, antimicrobial, and wound-healing activity. Regarding the side effects of drugs conventionally used for inflammatory bowel disease (IBD) treatment, we investigated the anticolitis properties of aqueous (SSAE) and hydroalcoholic (SSHE) extracts of S. striata on experimental colitis. Materials and Methods: The colitis was induced using acetic acid (3%) and 2 h before ulcer induction, each group of rats received orally three doses (150, 300, and 600 mg/kg, p.o.) of SSAE or SSHE for the next 5 days. Dexamethasone (1 mg/kg, i.p.) and mesalazine (100 mg/kg, p.o.) were used as reference drugs. Different parameters including weight of colon/height, ulcer index, total colitis index, levels of myeloperoxidase (MPO) and malondialdehyde (MDA) were investigated. Results: Total phenolic contents were 4.3 ± 0.2 and 7.1 ± 0.4 mg/g equivalent to gallic acid for SSAE and SSHE respectively. Three applied doses of SSHE and the highest dose of SSAE (600 mg/kg) could reduce all the macroscopic and pathologic indices of colitis and the levels of MPO and MDA. Two lesser doses of SSAE (150, 300 mg/kg) however, couldn't diminish the histopathologic features of colitis and the values of MPO and MDA. Conclusions: S. striata, especially SSHE, which also contained more phenolic compounds, had an ameliorating effect on ulcerative colitis and possibly exerts this effect through its antioxidant, antiinflammatory and wound healing properties. Further investigations are required to introduce this plant as a novel alternative herbal drug for colitis treatment.

Alleviation of cholestatic liver injury and intestinal permeability by lubiprostone treatment in bile duct ligated rats: role of intestinal FXR and tight junction proteins claudin-1, claudin-2, and occludin.

Gut barrier disintegrity and endotoxin translocation to the liver and systemic circulation are serious clinical complications associated with the stoppage of intestinal bile flow. There is no precise pharmacological option to prevent increased intestinal permeability after bile duct ligation (BDL). Lubiprostone, a chloride channel-2 agonist, has been shown to accelerate restoration of epithelial barrier dysfunction caused by injury, but the exact mechanisms underlying the beneficial effects of lubiprostone on intestine barrier integrity remain unknown. Here, we assessed the beneficial effect of lubiprostone on cholestasis caused by BDL and relevant mechanisms. Male rats were subjected to BDL for 21 days. Seven days after BDL induction, lubiprostone was administered twice daily (10 µg/kg of body weight). Intestinal permeability was assessed through measurements of serum lipopolysaccharide (LPS) concentration. Real-time PCR was conducted to assess expression of intestinal claudin-1 occludin and FXR genes, which are important in preserving the intestinal epithelial barrier integrity, as well as claudin-2 being involved in a leaky gut barrier. Histopathological alterations were also monitored for liver injury. Lubiprostone significantly decreased BDL-induced systemic LPS elevation in rats. BDL induced a significant reduction in FXR, occludin, and claudin-1 genes expression, while increased claudin-2 expression in rat colon. Treatment with lubiprostone significantly restored expression of these genes to the control values. BDL also increased the level of hepatic enzymes ALT, ALP, AST, and total bilirubin, while lubiprostone could preserve the hepatic enzymes and total bilirubin in the treated BDL rats. Lubiprostone also caused a significant reduction in BDL-induced liver fibrosis and intestinal damage in rats. Our results suggest that lubiprostone favorably prevents BDL-induced alterations in intestinal epithelial barrier integrity possibly via modulating intestinal FXRs and tight junction gene expression.

Impact of magnesium sulfate therapy in improvement of renal functions in high fat diet-induced diabetic rats and their offspring.

The role of magnesium sulfate (MgSO4) administration to prevent diabetic nephropathy (DN) by reducing insulin resistance (IR) and the relationship of this action with gender and the expression of NOX4 and ICAM1 genes in the parents and their offspring were studied. Males and females rat, and their pups were used. Type 2 diabetes induced by high-fat diet (HFD) administration and a low dose of streptozotocin. Animals were divided into the: non-treated diabetic (DC), the diabetic group received insulin (Ins), and the diabetic group received MgSO4. Two groups of parents received just a normal diet (NDC). Following each set of parents for 16 weeks and their pups for 4 months, while eating normally. We assessed the amount of water consumed, urine volume, and blood glucose level. The levels of glucose, albumin, and creatinine in the urine were also measured, as well as the amounts of sodium, albumin, and creatinine in the serum. Calculations were made for glomerular filtration rate (GFR) and the excretion rates of Na and glucose fractions (FE Na and FE G, respectively). The hyperinsulinemic-euglycemic clamp was done. NOX4 and ICAM1 gene expressions in the kidney were also measured. MgSO4 or insulin therapy decreased blood glucose, IR, and improved GFR, FE Na, and FE G in both parents and their offspring compared to D group. MgSO4 improved NOX4 and ICAM1 gene expressions in the parents and their offspring compared to D group. Our results indicated that MgSO4 could reduce blood glucose levels and insulin resistance, and it could improve kidney function.

Preparation, physicochemical, and retinal anti-angiogenic evaluation of poloxamer hydrogel containing dexamethasone/avastin-loaded chitosan-N-acetyl-L-cysteine nanoparticles.

This study was meant to describe a Poloxamer hydrogel combining Chitosan-N-acetyl-L-cysteine (CNAC) nanoparticles to increase loading and sustained intravitreal administration of Avastin macromolecule. To increase the drug's efficacy and reduce the interfacial fluid pressure in a formulation, dexamethasone was used. To do so, CNAC was synthesized. Then, Avastin- loaded CNAC nanoparticles were prepared and optimized. The resulting hydrogel's sol-gel transition time and viscosity were determined using poloxamer and hydroxypropylmethylcellulose (HPMC). In vitro and in vivo investigations of Avastin-loaded CNAC nanoparticles and hydrogel comprising dexamethasone/Avastin-loaded CNAC nanoparticles were determined. In vitro, the drug release profile of optimized hydrogel containing Avastin-loaded CNAC nanoparticles was sustained and controlled over 256 h. The obtained results point to poloxamer/HPMC (18 %/0.5 %) as the best formulations for this hydrogel to develop a sol-gel transition. About 97 % of dexamethasone was released from the hydrogel within 18 h. In vivo results indicated that the optimized formulation compared with free Avastin could improve Diabetic retinopathy (DR). Consequently, we infer that this new drug delivery method may enhance Avastin intravitreal administration, lowering the frequency, danger, and expense of heavy intravitreal injections and resulting in improved treatment of posterior eye segment neovascularization and concomitant vitreoretinal disorders.

Salvia officinalis leaf extracts protect against acute colitis in rats.

Background and purpose: Inflammatory bowel disease (IBD) is a chronic and multifactorial disease with unknown etiology and a decisive cure. Salvia officinalis (sage) which has anti-inflammatory, anti-oxidative, and ulcer healing properties can be useful for the treatment of IBD. Therefore, the effect of S. officinalis ethanolic extract (SOEE) and methanolic partition (SOMP) was investigated on acetic acid-induced ulcerative colitis. Experimental approach: Male Wistar rats (180-220 g) were used. SOEE (30, 60, and 120 mg/kg) and SOMP (50, 100, and 150 mg/kg) were prepared through maceration method. Prepared extracts, dexamethasone (1 mg/kg, i.p.), and mesalamine (100 mg/kg) as reference drugs and normal saline as control were administered by gavage, 2 h before colitis induction and preserved for four further days to animals. The colon tissues were examined for macroscopic and pathologic parameters and myeloperoxidase (MPO) and malondialdehyde (MDA) levels. Findings/Results: SOEE (60 and 120 mg/kg) and SOMP at all doses alleviated colitis severity and indices both in macroscopic and microscopic views. MDA and MPO activities were also significantly declined in the extracts-treated groups compared to the controls. The lowest dose of SOEE couldn't meaningfully reduce any of the parameters compared to the control group. Conclusion and implications: Both extracts of S. officinalis exerted anti-colitis effects in rats, though methanolic partition was more effective, especially at the highest dose. It seems S. officinalis could exert protection against oxidative stress and inflammatory mediators in colitis tissue. More experimental and clinical studies are required to explore the exact mechanisms and active ingredients which are involved.

Preparation of a biomimetic bi-layer chitosan wound dressing composed of A-PRF/sponge layer and L-arginine/nanofiber.

To better mimic the structure of skin tissue, the use of a multi-layered wound dressing has been proposed. In the present study, a sponge-nanofibrous bi-layer dressing is designed. For this purpose, a chitosan/polyethylene glycol (CsPEG) sponge with advanced platelet-rich fibrin (A-PRF) was prepared as the upper layer of wound dressing, and a Cs/L-arginine electrospun nanofiber layer as the bottom layer. After physical, chemical and mechanical evaluations, the release of platelet-derived growth factor-AB (PDGF-AB), vascular endothelial growth factor (VEGF) and L-arginine were investigated. The antibacterial activity, cell viability and attachment of Bi-layer1.5 dressing (CsPEG/1.5A-PRF sponge coated with Cs/0.5 L-arginine nanofibers) were significantly higher than other dressings. Also, Bi-layer1.5 dressing increased the angiogenic potential and accelerated the wound healing, compared to other samples. Given the promising obtained results, the use of Bi-layer1.5 wound dressing with the ability to release growth factors and L-arginine is highly recommended to treat full-thickness wounds.

Intravenous Administration of Cisplatin with Magnesium Sulfate Supplement May Prevent Kidney Toxicity in Rats: The Role of Gender and Magnesium Sulfate Dose.

BACKGROUND: Cisplatin (CP) is widely used to treat various kinds of malignancies, but to avoid its side effects of nephrotoxicity and hypomagnesemia, magnesium supplementation is a subject of debate. The current study was designed to determine the protective role of intravenous magnesium sulfate (MgSO4) against intravenous administration of CP in male and female rats. METHOD: In this case-control experimental study, 80 Wistar male and female rats in 12 groups of experiments were subjected to receive intravenous administration of CP accompanied with intravenous infusion of different doses (1, 3, and 10 mg/ml solution) of MgSO4 and were compared with the control groups. RESULTS: CP administration increased blood urea nitrogen (BUN), creatinine (Cr), kidney tissue damage score (KTDS), and kidney weight (KW), and they were attenuated by the mid-dose of MgSO4 supplementation in female rats. However, in male rats, the increase of Cr, BUN, KTDS, and KW induced by CP was ameliorated by low, mid-, and high doses of MgSO4 supplements. The levels of these markers were significantly different between male and female rats in the mid-dose of MgSO4-treated group (BUN: P=0.002, Cr: P=0.005, KTDS: P=0.002, and KW: P=0.031). CP reduced clearance of Cr (ClCr) in both male and female rats significantly compared to the control group of saline alone (P male = 0.002 and P female = 0.001), and the mid- and high doses of MgSO4 supplements improved ClCr in female rats. There were also sex differences in ClCr in mid- (P=0.05) and high (P=0.032) doses of MgSO4-treated groups. CP accompanied with the mid-dose of MgSO4 supplement reduced the KTDS (P male = 0.04 and P female = 0.004) and KW (P male = 0.002 and P female = 0.042) in both male and female rats significantly when compared with the CP-alone-treated group, while there were also significant differences between the sexes (KTDS: P=0.002 and KW: P=0.031). CP accompanied with three different doses of MgSO4 supplements did not improve the serum levels of lactate dehydrogenase, urine level of sodium, malondialdehyde, urine flow, and nitrite statistically when compared with the CP-alone-treated group. CONCLUSION: The renal protective effect of MgSO4 could be dose and gender related.

Combination Therapy with GABA and MgSO4 Improves Insulin Sensitivity in Type 2 Diabetic Rat.

BACKGROUND: Gamma-aminobutyric acid (GABA) and magnesium sulfate (MgSO4) play a crucial role in glycemic control. Therefore, we studied the effect of combination therapy with GABA and MgSO4 to improve insulin sensitivity in diabetes induced by streptozotocin as well as high-fat diet in a diabetic rat model. Design and Methods. Forty randomly selected rats were assigned to four groups: nondiabetic control group was fed the normal diet, insulin-resistant diabetic rat model was induced by streptozotocin and high-fat diet, GABA + MgSO4 group received GABA and MgSO4, and insulin group was treated with insulin. Body weight, abdominal fat, blood glucose, serum insulin, and glucagon concentration were measured. The glucose clamp technique, glucose tolerance test, and insulin tolerance test were performed to study insulin sensitivity. Also, the expressions of glucose 6 phosphatase, glucagon receptor, and phosphoenolpyruvate carboxykinase genes in liver were assessed for the gluconeogenesis pathway. Protein translocation and glucose transporter 4 (Glut4) genes expression in muscle were also assessed. RESULTS: Combination of GABA + MgSO4 or insulin therapy enhanced insulin level, glycemic control, glucose and insulin tolerance test, some enzymes expression in the gluconeogenesis pathway, body fat, body weight, and glucagon receptor in diabetic rats. Moreover, an increase was observed in protein and gene expression of Glut4. Insulin sensitivity in combination therapy was more than the insulin group. CONCLUSIONS: GABA and MgSO4 enhanced insulin sensitivity via increasing Glut4 and reducing the gluconeogenesis enzyme and glucagon receptor gene expressions.

Ulcer-Healing Effect of Hydroalcoholic Extract and Essential Oil of Achillea millefolium L. on Murine Model of Colitis.

Bakground: Ulcerative colitis (UC) is an inflammatory bowel disease that can be treated with many medications but they have various side effects and low cure rate. So, the need for finding novel drugs with better healing characters and less toxicity would be mandatory. Achillea millefolium (A. millefolium, Yarrow) has been traditionally used to treat bleeding, ulcers, wounds, liver, and bile disorders, and recently it has been shown to have anti-ulcer, analgesic, anti-inflammatory, antioxidant, and appetizing effects that make it as a good candidate for UC. Methods: UC was induced with intra-rectal instillation of acetic acid. A. millefolium hydroalcoholic extract (AMHE, 200, 400, and 600 mg/kg/day) and essential oil (AMEO, 62.5, 125, and 250 µl/kg/day) were given to six groups of male Wistar rats for 5 days. Dexamethasone (1 mg/kg/day, intra-peritoneal) and mesalazine (100 mg/kg/day, orally) were used as reference drugs. Colon tissue specimens were separated for assessing macroscopic, pathologic, and biochemical markers. Results: For AMHE, 77.2 mg/g equivalent to gallic acid was obtained for total phenols. Main assessed markers, including ulcer index, total colitis index, colon weight/length ratio, rats' weight gain, and malondialdehyde levels were significantly improved in AMHE (400 and 600 mg/kg/day) and AMEO (125 and 250 µl/kg/day) groups compared to controls. Myeloperoxidase activity was only attenuated in AMHE groups significantly. Conclusions: Both AMHE and AMEO were effective in healing experimental colitis. It seems antioxidant, anti-inflammatory, and anti-ulcer activities of Yarrow are responsible for these beneficial effects. Further studies are warranted to elucidate the exact mechanisms involved.

Hydration with Mannitol and Dextrose May Promote Cisplatin-Induced Nephrotoxicity: Test of Five Protocols of Hydration during Cisplatin Therapy in Rat Models.

BACKGROUNDS: Cisplatin (CP) still is a novel choice for solid tumor therapy, but it is accompanied with the side effect of nephrotoxicity. Hydration may reduce the risk of CP-induced nephrotoxicity, while the issue is still challenging. In this study, five types of hydration protocols including saline, mannitol, dextrose saline, saline plus furosemide, and saline plus mannitol were examined in both sexes of rats during CP therapy. METHODS: Seventy-six male and female Wistar rats in 14 groups of experiments were subjected to CP therapy, and five types of hydration protocols were implemented, and the induced nephrotoxicity was evaluated via biochemical markers, kidney function parameters, and pathology investigation. RESULTS: Male and female rats had different responses to hydration protocol types. The higher mortality rate was seen in female rats that received mannitol or dextrose hydration types. In addition, the serum levels of blood urea nitrogen (BUN) and creatinine (Cr) and sodium excretion fraction (ENa%) increased and the clearance of Cr (ClCr) decreased significantly (P < 0.05) in female rats hydrated with saline plus furosemide or mannitol plus saline-treated groups. The worsened condition in male rats is observed in the mannitol hydration group with a significant decrease of ClCr and significant increase of serum BUN and Cr and ENa% (P < 0.05). The higher kidney tissue damage score (KTDS) in the mentioned groups verified the findings. CONCLUSION: Hydration with mannitol or dextrose promotes the risk of nephrotoxicity during CP therapy with more intensity on the female.

Comparative evaluation of BMI-1 proto-oncogene expression in normal tissue, adenoma and papillary carcinoma of human thyroid in pathology samples.

OBJECTIVE: Papillary Thyroid carcinoma accounts for more than 60% of adult thyroid carcinomas. Finding a helpful marker is vital to determine the correct treatment approach. The present study was aimed to evaluate the expression of the B cell-specific Moloney murine leukemia virus integration site 1 (BMI-1) gene in papillary carcinoma, adenoma, and adjacent healthy thyroid tissues. Pathology blocks of thyroid tissues at the pathology department of patients who have undergone thyroid surgery between 2015 and 2019 were examined; papillary carcinoma, adenoma, and healthy tissues were selected and sectioned. Total RNA was extracted, and the relative expression level of the BMI-1 gene was examined using the Real-Time qPCR method. RESULTS: In the papillary and adenoma tissues, BMI-1 was overexpressed (1.047-fold and 1.042-fold) in comparison to healthy tissues (p < 0.05 for both comparisons). However, no statistically significant differences were observed between adenoma and papillary carcinoma tissues regarding BMI-1 gene expression. This study demonstrated a new biomarker for thyroid malignancies and found that the mRNA levels of the BMI-1 gene were higher in tumor tissues compared with healthy tissues. Further studies are needed to evaluate the BMI1 gene expression in other thyroid cancers.

Endurance exercise improves avoidance learning and spatial memory, through changes in genes of GABA and relaxin-3, in rats.

Different exercise patterns, neurotransmitters, and some genes have numerous effects on learning and memory. This research aims to investigate the long-term effects of submaximal aerobic exercise on spatial memory (SM), passive avoidance learning (PAL), levels of serum relaxin-3, gamma-aminobutyric acid (GABA), RLN3 gene, and glutamic acid decarboxylase (GAD65/67 genes) in the brainstem of adult male Wistar rats. Fifty male Wistar rats were randomly divided into five groups: aerobic exercise groups, performed on a treadmill running (TR), for 5 weeks (Ex5, n = 10), 10 weeks (Ex10, n = 10), involuntary running wheel group for 5 weeks (IRW5, n = 10), sham (Sh, n = 10) and control (Co, n = 10). Consequently, SM, PAL, serum relaxin-3, GABA, and GAD65/67 and RLN3 genes were measured by ELISA and PCR. Ex5, Ex10 and IRW5 improved significantly SM (p ≤ 0.05), PAL (p ≤ 0.001) and decreased significantly relaxin-3 (p ≤ 0.001). RLN3 in the brain also decreased. However, it was not significant. GABA and GAD65/GAD67 increased significantly (p ≤ 0.05) in Ex5, Ex10 compared to Sh and Co. Aerobic exercise enhanced SM and PAL in Ex compared to Co and Sh. However, duration and type of exercise affected the level of enhancement. The serum relaxin-3 and RLN3 gene displayed reverse functions compared to GABA and GAD65/67 genes in Ex. Therefore, the changes of neurotransmitters in serum relaxin-3, GABA, and their genes: RLN3 and GAD65/67 respectively, influenced learning and memory meaningfully.

Fabrication and evaluation of hesperidin loaded polyacrylonitrile/polyethylene oxide nanofibers for wound dressing application.

In this study, hesperidin (HPN) loaded polyacrylonitrile (PAN)/polyethylene oxide (PEO) electrospun nanofibers were prepared for use as wound dressing. Accordingly, HPN loaded hybrid nanofibers were generated via electrospinning. A full factorial design was then applied to evaluate the influence of formulation variables including PEO amount, HPN amount and total polymer amount on the nanofiber features. Fabricated membranes were evaluated in terms of morphology, diameter, entrapment efficiency (EE) %, drug loading (DL) %, release efficiency (RE) %, swelling % and mechanical properties. Analysis of the obtained data showed that the amount of PEO was the most effective factor impacting the swelling and release percentage; by raising the amount of PEO from 20% to 40%, the swelling % and release rate were considerably increased. The optimized nanofibers were found to be non-beaded, smooth and cylindrical with fiber diameter of 126.14 ± 23.96 nm, EE% of 38.58 ± 6.06, DL% of 5.36 ± 0.83, swelling % of 859.90 ± 33.49, RE % of 78.49 ± 0.21, UTS of 0.79 ± 0.13 MPa and Young's moduli of 20.91 ± 2.13 MPa. The physical state of HPN in optimized hybrid nanofibers was examined and the related XRD analysis revealed that HPN was either molecularly dispersed, or it existed in an amorphous state in the nanofibers. The in vivo studies also demonstrated that the wound healing rate in the case of HPN loaded nanofibers was higher when compared with other groups. Moreover, according to H&E and MT stain results, HPN loaded nanofibers did promote the regeneration of skin more effectively, as compared with HPN-free nanofibers. Overall, HPN loaded nanofibers mats prepared in this study have the potential to serve as wound dressings.

Evaluation of the effect of hydroalcoholic and flavonoid-enriched extracts of Dracocephalum kotschyi on indomethacin-induced gastric ulcer in rats.

BACKGROUND AND PURPOSE: Dracocephalum kotschyi (Zaringiah) is a fragrant wild medicinal plant found in Iran. Traditionally, it is used for the treatment of rheumatism, asthma, and gastrointestinal ailments. So far no investigation has been done on the beneficial or side effects of D. kotschyi on peptic ulcer. Therefore, this research was performed to find out whether D. kotschyi extract would induce peptic ulcer or could alleviate existing peptic ulcer. EXPERIMENTAL APPROACH: Effect of hydroalcoholic (DKHE) and flavonoid extracts (DKFE) of D. kotschyi were determined in normal or indomethacin-induced gastric ulcer rats (n = 6) and compared with the vehicle and ranitidine treated controls. All the treatments were carried out orally and 24 h later the stomach mucus was visually examined for peptic ulcers. A section of the stomach was taken for microscopic histopathological examinations while another section of the stomach was used for measurement of myeloperoxidase (MPO) and malondialdehyde (MDA) activities. FINDINGS/RESULTS: Oral administration of the DKHE and DKFE alone, did not cause any sign of gastric ulcer induction. The D. kotschyi extracts not only didn't aggravate the induced ulcer but also significantly prevented the severity of gastric ulcer induction by indomethacin. In addition, DKHE and DKFE inhibited MPO (up to 58.2%) and MDA (up to 44.2%) activities indicating their anti-inflammatory and antioxidant potential action on the stomach-induced ulcer. CONCLUSION AND IMPLICATION: Usage of D. kotschyi extracts is not associated with gastric ulcer induction and its co-administration with NSAIDs would be beneficial for controlling both the inflammation and preventing gastric ulcer in diseases such as rheumatism.

Protective Role of Angiotensin II Type 1 Receptor Blocker on Short Time Effect of Oleic Acid Induced Lung and Kidney Injury.

BACKGROUNDS: Acute respiratory distress syndrome (ARDS) causes high mortality rate in clinic, and the pathogenesis of this syndrome may interact with renin angiotensin system (RAS) components. The main objective of this study was to determine the protective role of AT1R antagonist (losartan) on oleic acid (OA) induced ARDS and kidney injury. METHODS: The animal model of ARDS was performed by intravenous administration of 250 µl/kg oleic acid (OA). Male and female rats were subjected to received intravenously vehicle (saline, groups 1 and 4), OA (groups 2 and 5), or losartan (10 mg/kg) plus OA (groups 3 and 6), and six hour later, the measurements were performed. RESULTS: Co-treatment of OA and losartan increased the serum levels of blood urea nitrogen significantly (P < 0.05) and creatinine insignificantly in both gender. However, the OA induced kidney damage was decreased by losartan significantly in male (P < 0.05) and insignificantly in female rats. In addition, co-treatment of OA and losartan decreased lung water content significantly in male rats (P < 0.05). Based on tissue staining, no significant difference in lung tissue damages were observed between the groups, however some exudate were observed in lung male rats treated with OA alone which were abolished by losartan. CONCLUSIONS: Losartan may protect the kidney and lung against OA induced tissue injury in male rats. This protective action is not certain in female rats.

Combinatorial fluorapatite-based scaffolds substituted with strontium, magnesium and silicon ions for mending bone defects.

In bone tissue engineering, ionic doping using bone-related minerals such as magnesium (Mg) or strontium (Sr) is a promising strategy to make up for the inherent disadvantages (low solubility) of various apatite-based materials (such as fluorapatite (FAp) and hydroxyapatite (HA)). Therefore, some studies in recent years have tried to address the lack-of-methodology to improve the properties of bioceramics in the field. Even though the outcome of the studies has shown some promises, the influence of doped elements on the structures and properties of in-vitro and in-vivo mineralized FAp has not been investigated in detail so far. Thus, it is still an open question mark in the field. In this work, strontium modified fluorapatite (Sr-FAp), magnesium and silicon modified fluorapatite (Mg-SiFAp) bioceramics were synthesized using a mechanical alloying methodology. Results showed that the doped elements could decrease the crystallinity of FAp (56%) to less than 45% and 39% for Sr-FAp and Mg-SiFAp, respectively. Moreover, in-vitro studies revealed that Sr-FAp significantly enhanced osteogenic differentiation of hMSCs, after 21 days of culture, compared to Mg-SiFAp at both osteogenic and normal media. Then, in vivo bone formation in a defect of rat femur filled with a Sr-FAp and Mg-SiFAp compared to empty defect was investigated. Histological analysis revealed an increase in bone formation three weeks after implanting Sr-FAp compared to Mg-SiFAp and the empty defect. These results suggest that compared to magnesium and silicon, strontium ion significantly promotes bone formation in fluorapatite, making it appropriate for filling bone defects.

Protective Effect of Vitis vinifera (Black Grape) Seed Extract and Oil on Acetic Acid-Induced Colitis in Rats.

BACKGROUND: Vitis vinifera (black grape) is cultivated worldwide and has numerous oral and therapeutic applications. It has proven anti-inflammatory, antioxidant, antimicrobial, and wound healing properties. The aim of this study was to investigate the effect of black grape seed (hydroalcoholic) extract (BGSE) and black grape seed oil (BGSO) on experimental colitis. METHODS: BGSE (50, 100, and 200 mg/kg) and BGSO (2, 4, and 8 mL/kg) were administered orally (p.o.) in groups of six male Wistar rats, 2 h before induction of colitis and continued further for 4 days. Prednisolone (4 mg/kg) and mesalamine (100 mg/kg) were used as reference drugs. Weight/length of colons, macroscopic and histopathologic indices, and biochemical parameters including myeloperoxidase (MPO) and malondialdehyde (MDA) were evaluated. RESULTS: All doses of BGSE and BGSO significantly decreased the colon weight, ulcer index, and total colitis index in comparison with the control group, although greater doses of both fractions had more significant protection. Data of MPO activity revealed that all treated groups with the exception of BGSE (50 mg/kg) and BGSO (2 mL/kg) showed a meaningful decline in comparison with the control group. Concerning the MDA values in colonic tissue, it was demonstrated that BGSE (100, 200 mg/kg) and BGSO (8 mL/kg) caused a significant dip in this oxidative stress parameter. CONCLUSIONS: Oral administration of BGSE and BGSO had an appropriate anti-inflammatory effect and so could be considered as a suitable candidate for treating or preventing ulcerative colitis. Furthermore, detailed studies are warranted to explore the exact mechanism of action and clinical preference of these compounds.

A multifunctional nanocomposite spray dressing of Kappa-carrageenan-polydopamine modified ZnO/L-glutamic acid for diabetic wounds.

Sprayable bioadhesives with exceptional properties were developed for application in wound healing. In this study, a visible light-crosslinkable nanocomposite bioadhesive hydrogel with multifunctional properties was proposed. While methacrylated Kappa-carrageenan (KaMA), mimicking the natural glycosaminoglycan was applied as the hydrogel matrix, various concentrations of polydopamine modified ZnO (ZnO/PD) nanoparticles (0, 0.5, 1 and 2 wt%) was loaded in it to improve its mechanical, antibacterial and cellular properties. Moreover, L-glutamic acid was incorporated in the nanocomposite hydrogel network to accelerate wound healing. The nanocomposite hydrogels revealed significant mechanical property and recovery ability, comparable elasticity with human skin and great adhesiveness. For instance, the tensile strength of KaMA hydrogel enhanced from 64.1 ± 10 to 80.3 ± 8 kPa and elongation jumped from 20 ± 4% to 61 ± 5% after incorporation of 1 wt% ZnO/PD nanoparticles. The nanocomposite hydrogels demonstrated effectual blood clotting ability and biocompatibility, >95% cell viability after 3 days of incubation. In vivo experiments also suggested that L-glutamic acid loaded nanocomposite hydrogel considerably accelerated wound healing with superior granulation tissue thickness than control in a full-thickness skin defect model. Taken together, this visible-light crosslinking nanocomposite hydrogel with significant properties could be used to spray on a wound area to eliminate wound infection and accelerate wound healing process.