Investigating the effect of parasites (toxoplasma gondii RH strain, Leishmania major (MRHO/IR/75/ER), and hydatid cyst) antigens on Alzheimer's disease: An in vivo evaluation.

This study aimed to investigate the effects of parasite antigens on Alzheimer's symptoms in animal model. Alzheimer's model was induced in Wistar rats using Amyloid-beta peptide, and treated with parasite crude antigens from T. gondii RH strain, L. major (MRHO/IR/75/ER), and HC. Spectrophotometry and real-time PCR were used to evaluate the oxidative stress levels, antioxidant enzyme activity, and gene expression of NLRP3, IL-8, IL-1ß, and Caspase-1. Histological assays were performed to investigate structural changes in the hippocampus. Apoptosis was analyzed using an Annexin V Apoptosis by Flow cytometer. The levels of total oxidant, antioxidant, and SOD increased in the Alzheimer's group compared with the control group, but these factors were lower in the L. major group. The apoptosis in the treated groups was lower compared to the Alzheimer's group. IL-8 expression was significantly higher in all Alzheimer's groups, but decreased in the HC and L. major treated group compared to Alzheimer's. IL-1ß and Caspase-1 expression were similarly increased in all groups compared with the control group, but decreased in the antigen-treated groups compared with Alzheimer's. NLRP3 expression was increased in all groups compared with the control group, with lower expression in HC group, but significantly decreased in L. major group compared with Alzheimer's. In histological results, only L. major group could play a therapeutic role in pathological damage of the hippocampus. The results showed that parasite antigens, specifically L. major antigens, may have neuroprotective effects that reduce oxidative stress, apoptosis, and histopathological changes in response to AD in animal model.

Effect of vitamin D on cardiac hypertrophy in D-galactose-induced aging model through cardiac mitophagy.

BACKGROUND: Cardiac apoptosis plays a key role in increased morbidity associated with aging-induced-cardiac disorder. Mitochondria play an important role in cardiac apoptosis, and dynamin-related protein 1 (Drp1), as a main mediator of mitochondrial fission, can trigger the mitophagy process to sustain the mitochondrial quality. The present study was done to determine the effect of vitamin D (VitD) treatment on cardiac hypertrophy through mitophagy regulation in aged animals induced by D-galactose (D-GAL). METHODS AND RESULTS: Male Wistar rats were randomly divided into four groups: control, D-GAL (aging group), D-GAL co-injected with VitD (D-GAL ± VitD), and D-GAL plus ethanol (D-GAL ± Ethanol). Aging was induced by an intraperitoneal (i.p.) administration of D-GAL at 150 mg/kg daily for eight weeks and also VitD (400 IU/kg) or ethanol was injected (i.p.) into aging rats. Then, the levels of cardiac mitophagy and cardiac apoptosis were determined by measuring the expression of tensin homologue (PTEN)-induced putative kinase 1 (PINK1), Drp1, Bcl2-Associated X (Bax), and B-cell lymphoma 2 (Bcl2) genes. Aging in rats was associated with a reduction in mitophagy and also an increase in apoptosis of the heart through down-regulation of Drp1, PINK1, and Bcl2 genes and also up-regulation of Bax. However, VitD improved cardiac hypertrophy through cardiac mitophagy in D-GAL-induced aging rats. CONCLUSION: VitD can inhibit cardiac hypertrophy by an increase in mitophagy and a decrease in apoptosis in the aging heart. The illustration of the suggested mechanism underlying of Vitamin D in cardiac hypertrophy induced by aging.

The effects of AdipoRon on cytochrome P450-related gene expression, acute steroidogenic regulatory protein, and structure of ovary in polycystic ovary syndrome model.

PURPOSE: One of the most common causes of infertility in adult women is polycystic ovary syndrome (PCOS) which has been identified with symptoms such as chronic hyperandrogenism, anovulation, and polycystic ovaries. Adiponectin modulates steroidogenesis and the expression of ovulation-related genes. Herein, we assessed the effect of AdipoRon (adiponectin agonist) in the PCOS model mice. METHODS: The PCOS model was induced with letrozole in the adult female mice and the animals received intraperitoneal injection of AdipoRon (5 mg/kg) for 10 days. Expression of CYP11A, CYP17A, and CYP19A genes, StAR protein, and histomorphology of the ovary were evaluated using real-time RT-PCR, western blotting, and histochemistry methods, respectively. RESULTS: Although administration of letrozole caused an increase in the expression of CYP11A, CYP17A, and StAR and a decrease in the CYP19A1 expression, injection of AdipoRon reversed these changes. Moreover, AdipoRon treatment resulted in an improvement of folliculogenesis and a reduction of cysts compared to the letrozole-treated mice. CONCLUSION: It is likely that AdipoRon has protective effects on the PCOS through modulation of cytochrome P450-related genes and steroidogenesis but needs further study to be sure.

Dimedone nanoparticle as a promising approach against toxoplasmosis: In vitro and in vivo evaluation.

Toxoplasma gondii, an intracellular parasite, has shown drug resistance and therapeutic failure in recent years. Dimedone (DIM) has been introduced as a new chemical compound with anti-bacterial and anti-cancer properties. The aim of this study was to investigate the potential protective role of DIM nanoparticles in an animal model of toxoplasmosis. Cytotoxicity of DIM on Vero cell line assessed using MTT, and the effect of DIM on Toxoplasma gondii was evaluated by counting the number of parasites compared to the control group in vitro. The rate of pathogenesis and virulence of the parasite was checked on the liver cells of the animal model using hematoxylin-eosin staining. Furthermore, various parameters indicating oxidative stress were compared in mouse liver tissue in different groups. The release of the nanoparticle form was significantly longer than the free drugs. The IC50 of Nano-DIM was 60 µM and the reduction of intracellular parasite proliferation in the group Nano-DIM and Nano-PYR (Nano-primethamine) was significantly lower than the free drugs in vitro. Histopathology examination in the groups treated with dimedone nanomedicine showed that the degree of disintegration of the epithelium of the central vein of the liver and infiltration and vacuolization of liver cells were lower compared to the toxoplasmosis group. Additionally, the level of some oxidative stress indicators was observed to be lower in the nano-treated groups compared to other groups. The results of this study showed DIM can be used as a promising compound for anti-T. gondii activity and can prevent the proliferation of it in cells.

An Oxidative Stress Study on Curcumin and Nanocurcumin against Aluminum phosphide-induced Kidney Injury in Rats: The Role of SIRT1/FOXO3 Signaling Pathway in Nephrotoxicity.

INTRODUCTION: In this study, we have investigated the aluminium phosphide (ALP) toxicity on Renal Function and oxidative stress in kidney tissue of male rats and the possible protective role of Curcumin and nanoCurcumin against ALP-induced nephrotoxicity. METHODS: Thirty-six adult male rats were divided into 6 groups (n=6). ALP (2 mg/kg oral administration) and control groups received Curcumin and nanoCurcumin (oral administration 100 mg/kg ( or without it. After seven days of treatment, kidney parameters, oxidative stress biomarkers, and expression level of sirtuins1 (SIRT1)/Forkhead box protein O1 (FoxO1) pathway genes were evaluated in kidney tissue. In addition, histopathological changes in the kidney tissues were assayed. RESULTS: In the ALP group, compared to the control group, lipid peroxidation levels, urea, and creatinine were increased, and total antioxidant capacity and thiol groups decreased significantly P<0.05. In Curcumin and nanoCurcumin groups compared to the ALP group, lipid peroxidation and creatinine decreased significantly P<0.05. Also, Curcumin and nanoCurcumin improved the tissue damage caused by ALP. NanoCurcumin modulated the effect of ALP on the gene expression levels in SIRT1/FoxO1. CONCLUSION: The present study showed that ALP intoxication in kidney tissue can induce oxidative damage. Moreover, Curcumin and nanocurcumin, as potential antioxidants, can be effective therapeutics in ALP-induced nephrotoxicity.

The Effects of Resveratrol on Silica-Induced Lung Oxidative Stress and Inflammation in Rat.

Background: Chronic exposure to silica is related with the provocation of an inflammatory response and oxidative stress mechanism. Vitamin D has multiple benefits in biological activities particularly respiratory system disease. Method: In this research, 20 male Wistar rats were randomly allocated into four groups (5 rats /group) as follow: Group1 received saline as (negative control) group. The group 2 received a single IT instillation of silica (positive control) group; the group 3 was co-administrated with single IT silica and Vitamin D (20 mg/kg/day) daily for a period of 90 days. The rats of group 4 received Vitamin D daily for a period of 90 days. Results: Silica significantly increased serum and lung total Oxidant Status (TOS). Meanwhile, silica reduced serum and lung total antioxidant capacity (TAC), GSH and tumor necrosis factor-α (TNF-a). Vitamin D treatment meaningfully reversed oxidative stress, antioxidants status and inflammatory response. Also, Vitamin D improved histopathological changes caused by silica. Conclusion: These findings indicate that Vitamin D exerts protective effects against silica-induced lung injury. It seems that Vitamin D has potential use as a therapeutic object for silica induced lung injure.

Is nanoparaquat safer than bulk paraquat? An in vitro and in vivo evaluation.

Paraquat (PQ) is an herbicide which has brought some health problems through the production of reactive oxygen species. The increasing interest in the novel formulation of agrochemicals has been aiming to provide safety for non-target organisms. Chitosan is a well-known non-toxic polymer, commonly used in preparing particles via ionotropic gelation. In this study, we prepared PQ nanoparticles (PQNPs) and evaluated their toxicity in vivo and in vitro. PQNPs were prepared and characterized in two forms, with and without the utilization of chitosan. Relative cell survival of PQNPs were studied against bulk PQ in HEK-293. Also, the acute lung injury of PQNP was assessed against treatment with acetylcysteine. Total antioxidant capacity (TAC), lipid peroxidation (LPO), total thiol groups (TTG), and hydroxyproline, along with histological changes were assessed in the lungs. The size, zeta potential, and polydispersity index of the optimum particles were about 157.7 ± 7.03, 22.25 ± 4.52, and 0.701, respectively. The encapsulation efficiency was 65.11 ± 10.45, and the loading percent of PQ was 58.57 ± 2.37. PQNPs showed an initial burst of PQ release followed by a zero-degree pattern. PQNPs displayed lower cell cytotoxicity compared to bulk PQ. LPO, TAC, TTG, and hydroxyproline levels in lungs generally showed more satisfying status in PQNPQs as well. The levels of oxidative status markers indicate lower oxidative damage in lungs and a more desirable response to acetylcysteine treatment, in line with histological changes. PQ loaded in chitosan-alginate particles offers safer characteristics compared with bulk PQ.

The effects of polyvinyl alcohol-coated selenium nanoparticles on memory impairment in rats.

Some mineral elements exert beneficial neuroprotection, especially in the form of nanoparticles. The aim of the present study was to evaluate the effects of selenium nanoparticles (SeNPs) and polyvinyl alcohol (PVA)-coated SeNPs (PVA-SeNPs) on Alzheimer's disease (AD) in a rat model of AD. Twenty-eight rats were randomly divided into four groups of seven rats: control, Alz, Alz + Se, and Alz + Se-PV groups. PVA-SeNPs and SeNPs were chemically synthesized and orally administrated (0.4 mg/kg) to the AD rats for one month. AD was induced by an intracerebroventricular (ICV) injection of streptozotocin (STZ). The memory function was assessed by the novel object recognition (NOR) and passive avoidance learning (PAL) tests. The expression of hippocampal brain-derived neurotrophic factor (BDNF) and stress oxidative markers (MDA and TAC), and the number of amyloid-beta (Aß) plaques were assessed using ELISA kits, biochemical methods, and Congo red staining, respectively. The results of the behavioral tests showed that the discrimination index in the NOR test increased in the Alz + PVA-SeNPs group compared to the Alz group. Memory performance in the PAL task improved in the PVA-SeNPs and SeNPs groups compared to the Alz group. The level of the BDNF in both of the Alz treatment groups (PVA-SeNPs and SeNPs) showed a significant increase compared to the Alz group. MDA levels and Aß plaques decreased in both NPs-treated Alz groups, while TAC levels decreased in all Alz groups. PVA-SeNPs were more effective than SeNPs in the improvement of the cognition deficit. The results suggest that PVA-SeNPs improve the cognition and memory deficit induced by an ICV injection of STZ through a decrease in the number of Aß plaques and malondialdehyde levels and an increase in the BDNF levels.

Neuroprotective effects of crocin and crocin-loaded niosomes against the paraquat-induced oxidative brain damage in rats.

Paraquat (PQ) is a nonselective herbicide that induces oxidative reactions and multiple-organ failure on exposure. Crocin, a carotenoid obtained from saffron, has demonstrated many therapeutic effects against neural conditions because of its antioxidant properties. In this study, 30 male Wistar rats were divided into 6 groups to evaluate the protective effects of crocin and crocin-loaded niosomes (NC) against PQ in the brain. The levels of total antioxidant capacity (TAC), lipid peroxidation (LPO), total thiol groups (TTG), superoxide dismutase (SOD), and catalase (CAT) activity were measured as the markers of redox status. Histopathological changes in the CA1 region of the hippocampus were evaluated by cresyl violet staining. Results indicated that both crocin and NC were able to attenuate the adverse effects of PQ at the histopathological level, which was following the changes in LPO (P < 0.0001), TAC (P < 0.01), and TTG (P < 0.05) level. The activity of CAT (P < 0.01) and SOD (P < 0.01) could be restored either by crocin or NC. Also, results indicated that nanoformulation of crocin in niosomes appears to be more promising. In conclusion, both crocin and NC showed favourable effects of PQ in the brain of rats, and were determined to be excellent agents to prevent acute toxicities of PQ. Furthermore, these two compounds can be known to provide neuroprotection.

Hydroalcoholic Extract of Scrophularia Striata Attenuates Hypertrophic Scar, Suppresses Collagen Synthesis, and Stimulates MMP2 and 9 Gene Expression in Rabbit Ear Model.

Objectives: Hypertrophic scars (HSs) are caused by abnormal wound healing. To date, no standard treatment has been made available for HSs. Scrophularia striata has been reported to accelerate wound healing and has the potential to prevent HS formation. In this study, we investigated the anti-scarring effects of S. striata extract (SSE) in a rabbit ear model of scarring. Methods: In this study, New Zealand white rabbit (weight 2.3-2.5 kg) were used. In the prevention phase of the study, three test groups received 5%, 10%, and 15% ointments of SSE in the Eucerin base, the fourth group received Eucerin, and the fifth group received no treatment. The samples were obtained on day 35 after wounding. In the treatment phase of the study, the test groups received an intralesional injection of SSE (5%, 10%, and 15%), the fourth group received an intralesional injection of triamcinolone, the fifth group received a solvent (injection vehicle), and the sixth group received no treatment. To evaluate the anti-scarring effects of SSE, the scar elevation index (SEI), epidermis thickness index (ETI), collagen deposition, and MMP2 and MMP9 gene expression were evaluated. Results: A significant reduction in SEI, ETI, and collagen deposition was noted in animals treated with SSE compared with the control groups. In addition, topical SSE stimulated MMP2 and MMP9 gene expression. Conclusion: The findings of this study demonstrate the potential for SSE in the prevention and treatment of HS. SSE could be prepared as an appropriate formulation to treat wounds and prevent abnormal scarring.

Co-Delivery of Doxycycline and Hydroxychloroquine Using CdTe-Labeled Solid Lipid Nanoparticles for Treatment of Acute and Chronic Brucellosis.

Brucellosis is a systemic disease in both acute and chronic forms which can affect any organ or tissue in the body. One of the biggest issues in treating this disease is its relapse. In this study, a complete treatment of brucellosis was evaluated using enhanced performance of doxycycline and hydroxychloroquine drugs by using solid lipid nanoparticles (SLN) conjugated cadmium-telluride quantum dots. The double emulsion method was used to prepare SLN and cadmium-telluride quantum dots. The physicochemical properties of NPs were determined. The effect of nanoparticle-loaded antibiotics against Brucella melitensis was determined by well diffusion, minimum inhibitory concentration (MIC), cell culture, and animal studies. The means of particle size, PDI, zeta potential, drugs loading, and encapsulation efficiency were 214 ± 25 nm, 0.385 ± 0.022, -18.7 ± 2.3 mV, 17.7 ± 1.5%, and 94.15 ± 2.6%, respectively. The results of FTIR and DSC showed that no chemical reaction occurred between the components of the NPs. The effect of free drug and NPs on bacteria was the same by well diffusion and MIC method. Drug-loaded NPs significantly reduced the number of CFUs in the cell line and acute and chronic brucellosis compared to the free drug. In conclusion, the synthesized nanoparticles were safe and green. With the slow release of the drug (100 h), the accumulation of the drug at the bacterial site increases and causes a greater effect on the B. melitensis and improves the disease of brucellosis. The use of synthesized nanodrugs in this study had promising therapeutic results.

Evaluation of Protective Effects of Curcumin and Nanocurcumin on Aluminium Phosphide­Induced Subacute Lung Injury in Rats: Modulation of Oxidative Stress through SIRT1/FOXO3 Signalling Pathway.

OBJECTIVE: Aluminum phosphide (AlP) is widely used to protect stored food products and grains from pests and rodents. The availability of AlP, especially in Asian countries it has become a desirable factor to commit suicide. The phosphine produced from ALP is a very reactive radical and a respiratory inhibitor that causes oxidative damage. There is no dedicated antidote or effective drug to manage AlP-induced lung toxicity. The present study aims to evaluate and compare the protective effects of curcumin and nanocurcumin on ALP­induced subacute lung injury and determine the underlying mechanism. METHODS: Rats were exposed to AlP (2 mg/kg/day, orally)+curcumin or nanocurcumin (100 mg/kg/day, orally) for 7 days. Then rats were anesthetized and lung tissues were collected. Oxidative stress biomarkers, genes expression of antioxidant enzymes, participated genes in the SIRT1/FOXO3 pathway, and lung histopathology were assessed by biochemical and ELISA methods, Real-Time PCR analysis, and H&E staining. RESULTS: Curcumin and nanocurcumin produced a remarkable improvement in AlP-induced lung damage through reduction of MDA, induction of antioxidant capacity (TAC, TTG) and antioxidant enzymes (CAT, GPx), modulation of histopathological changes, and up-regulation of genes expression of SIRT1, FOXO3, FOXO1 in lung tissue. CONCLUSION: Nanocurcumin had a significantly more protective effect than curcumin to prevent AlP-induced lung injury via inhibition of oxidative stress. Nanocurcumin could be considered a suitable therapeutic choice for AlP poisoning.

Impacts of garlic extract on testicular oxidative stress and sperm characteristics in type 1 and 2 diabetic rats: An experimental study.

BACKGROUND: Hyperglycemia damages various tissues such as the testes through oxidative stress and inflammation, which can eventually lead to infertility. OBJECTIVE: Garlic extract effects on the testicular tissue of diabetic rats were investigated. MATERIALS AND METHODS: In this experimental study, 36 male Wistar rats (8-wk old, weighing 230-300 gr) were randomly divided into 6 groups (n = 6/each) including; C: control rats, G: received 0.4 gr of garlic extract/100 gr body weight, D1: Streptozotocin-induced-diabetic rats or type 1, D1+G: D1 rats that were treated with garlic, D2: Streptozotocin + nicotinamide-induced-diabetic rats or type 2, D2+G: D2 rats treated with garlic. At the end of the study, serum testosterone was assayed by ELISA. Also, sperm quality and quantity were evaluated. For determination of oxidative stress status, total antioxidant capacity, total oxidative status, lipid peroxidation, and thiol groups were assayed in the testis tissues of the rats by colorimetric methods. Also, inducible nitric oxide synthase (iNOS) gene expression and the protein level of interleukin-1 ß (IL-1 ß ) were determined by quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. RESULTS: In diabetic rats, glucose, total oxidative status and lipid peroxidation, iNOS gene expression, and IL-1 ß were higher than in non-diabetic rats, whereas testosterone, total antioxidant capacity and thiol groups, and sperm quality were significantly lower compared with control rats. These alterations were normalized by garlic intervention. CONCLUSION: In diabetic rats, garlic was associated with reduced glucose, oxidative stress, IL-1 ß , and iNOS gene expression and increased testosterone and sperm quality. So, the results suggest that garlic can reduce the severity of damage in testicular tissues of diabetic rats through its hypoglycemic, antioxidant, and anti-inflammatory properties.

Antiapoptotic and antioxidative effects of cerium oxide nanoparticles on the testicular tissues of streptozotocin-induced diabetic rats: An experimental study.

BACKGROUND: Cerium dioxide nanoparticles (CNPs) due to the antidiabetic and antioxidant activities are proposed for the treatment of oxidative stress-associated diseases. OBJECTIVE: To examine the impact of CNPs on hyperglycemia-induced apoptosis and oxidative stress in the testis of diabetic rats. MATERIALS AND METHODS: Twenty-four male rats were divided into four groups (n = 6/each) as diabetic rats, CNPs group, diabetic + CNPs rats, and controls. The control group was fed only mouse food and water. Rats became diabetic through receiving streptozotocin (STZ) 60 mg/kg. CNPs were given to the rats at a dose of 30 mg/kg daily for 2 wk. Malondialdehyde and total thiol group (TTG) levels were measured using spectrofluorometer. Expression of b-cell lymphoma protein 2-associated X protein (BAX) and b-cell lymphoma protein 2 (Bcl-2) were investigated using quantitative real-time polymerase chain reaction. Western blot analysis was used to examine caspase 3 protein levels. RESULTS: The content of malondialdehyde significantly increased in the STZ-diabetic rats, while TTG levels demonstrated a remarkable decrease. Caspase-3, BAX, and BAX/Bcl-2 mRNA ratio raised significantly in the STZ-diabetic rats. On the other hand, Bcl-2 mRNA levels reduced in the testis of diabetic rats (p = 0.006). Intervention with CNPs caused a substantial increase in the TTG levels, while the malondialdehyde contents, caspase-3, BAX levels, as well as BAX/Bcl-2 mRNA ratio were considerably decreased following CNPs treatment. Administration of CNPs increased mRNA levels of Bcl-2 (p < 0.0001). CONCLUSION: CNPs treatment attenuates testicular apoptosis and oxidative stress induced by diabetes. This nanoparticle might be suggested for the treatment of diabetes-associated reproductive disorders.

Evaluation of the hepatoprotective effects of curcumin and nanocurcumin against paraquat-induced liver injury in rats: Modulation of oxidative stress and Nrf2 pathway.

Paraquat (PQ) is a widely used herbicide all over the world, which is highly toxic for animals and humans. Its cytotoxicity is based on reactive radical generation. The aim of this study is to evaluate and compare the hepatoprotective effects of curcumin and nanocurcumin against liver damage caused by sub-acute exposure with PQ via modulation of oxidative stress and genes expression of nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. Rats were exposed to PQ (5 mg/kg/day, orally) + curcumin or nanocurcumin (100 mg/kg/day, orally) for 7 days. Then rats were anesthetized and serum and liver samples were collected. Next, serum enzymatic activities, liver histopathology, oxidative stress, and expression of genes involved in Nrf2 signaling pathway were assessed by biochemical and enzyme-linked immunosorbent assay methods, hematoxylin and eosin staining, and real-time polymerase chain reaction analysis. PQ significantly increased malondialdehyde, alanine transaminase, aspartate aminotransferase, alkaline phosphatase levels, and Kelch-like ECH-associated protein 1 gene expression and also decreased total antioxidant capacity, total thiol group levels, Glutathione S-transferases, heme oxygenase 1, Nrf2, and NAD(P)H:quinone oxidoreductase 1 genes expression, causing histological damages to liver tissue. These changes were significantly modulated by curcumin and nanocurcumin treatments. Our findings showed that nanocurcumin had better hepatoprotective effect than curcumin in liver damage after PQ exposure most likely through modulation of oxidative stress and genes expression of Nrf2 pathway.

The effect of Staphylococcus aureus on the antibiotic resistance and pathogenicity of Pseudomonas aeruginosa based on crc gene as a metabolism regulator: An in vitro wound model study.

BACKGROUND: The cooperation of Pseudomonas aeruginosa and Staphylococcus aureus in various infections results in increased pathogenicity and antibiotic resistance. However, the mechanism controlling such a phenomenon is still unclear. In this study, the effects of S. aureus on the metabolism, antibiotic resistance, and pathogenicity of P. aeruginosa were investigated. MATERIAL AND METHODS: The biofilm and the planktonic states of growth of P. aeruginosa and S. aureus were investigated using the co-culture method in the L929 cell line. Then, the antibiotic resistance and virulence factors production of the recovered colonies of P. aeruginosa were examined by phenotypic methods. Quantitative Real-Time PCR was used to determine the expression level of crc, lasI/R, and rhlI/R genes. Two way ANOVA test and student's t-test were used to analyze the effect of S.aureus on metabolism, virulence, and resistance of P.aeruginosa. RESULTS: P. aeruginosa strains in a single-species planktonic culture on the L929 cell line indicated higher CFU counts than the biofilm. Conversely, in the biofilm state of co-culture, the CFU counts increased in comparison to the planktonic condition. Also, the expression level of crc increased two fold in the PA-1 and PA-2 strains compared to the single-species cultures on the L929 cell line. However, the PA-3 strain indicated a sharp decrease in the expression of crc (3 fold decrease). Besides, a 3-4 fold increase in susceptibility to amikacin was observed as the expression level of crc declined. The QS-regulated factors were diminished as rhlR and lasI were downregulated in both states of growth. CONCLUSION: In polymicrobial wound infection, Staphylococcus aureus plays a vital role in the metabolic changes of Pseudomonas aeruginosa. However, the levels of antibiotic susceptibility and pathogenicity of Pseudomonas aeruginosa also changed due to metabolism.

Coordination of las regulated virulence factors with Multidrug-Resistant and extensively drug-resistant in superbug strains of P. aeruginosa.

Successful pathogenicity often resulted from a complicated association between virulence and antibiotic resistance in Pseudomonas aeruginosa infections. Therefore, the current study aimed to investigate the relationship between the las system and antibiotic resistance. Seventy-three (73) P. aeruginosa isolates were collected from burn wounds (26.02%), blood cultures (30.13%), catheters (12.32%), and urine culture (31.50%). Among the 73 collected isolates, 22 isolates were considered as multi-drug resistant (MDR) and 11 isolates as extensively-drug resistant (XDR). Furthermore, phenazines and LasA protease were detected among 21.91% and 32.87% of isolates, respectively. Quantitative real-time PCR assessment of KPC, MBL, and lasI/R indicated that resistance and virulence factors are more expressed in XDR strains than MDR strains. Also, the expression level of KPC and MBL reduced in non-biofilm forming strains. However, increased expression levels of lasI, lasR, and the KPC genes were observed in LasA and LasB protease producing strains. Interestingly, 16 known sequence types (including ST108, ST260, ST217) and three novel STs (ST2452, ST2427, and ST2542) were characterized among the collected isolates, which are related to the virulence and resistance. In MDR-XDR strains, a strong correlation between lasI/R and the variants of antibiotic resistance genes was found. In conclusion, the pathogenicity of P. aeruginosa may increase the prevalence of antibiotic-resistant strains.

Comparison of the regenerative effects of bone marrow/adipose-derived stem cells in the Asherman model following local or systemic administration.

PURPOSE: Cell therapy is a promising strategy for the treatment of Asherman's syndrome (AS), but the origin of these cells and injection route influence the therapeutic effect and complications of cell therapy. Herein, we compared the effects of systemic or local intrauterine injection of bone marrow or adipose-derived mesenchymal stem cells (BMSCs/AMSCs) on the endometrium in a rat model of AS. METHODS: After induction of AS in adult Wistar rats, the CM-Dil-positive BMSCs or AMSCs were injected either locally or intravenously. After 3 weeks, endometrial thickness, collagen deposition, cell migration, and VEGF expression were evaluated using histochemistry/immunofluorescence studies. RESULTS: In all stem cell-treated groups, an ameliorative effect on the damaged endometrium was noted. Collagen deposition diminished in both groups (IV and local injection) compared to the AS model. In rats injected locally with MSC, fibrosis decreased compared to the other groups. Moreover, endometrial thickness increased in the groups that received local injection of BMSCs and AMSCs more than the IV-transplanted AMSCs group. Immunofluorescent staining demonstrated that although the systemic transplantation of BMSCs was more effective than the other groups on VEGF expression, it led to the lowest number of CM-Dil+ stem cells in the damaged endometrium. CONCLUSION: Stem cell transplantation may reconstruct the damaged endometrium, but it is recommended to select the most effective stem cells and injection route. Because the removal of the fibrosis and the replacement of the epithelia cells is an effective therapeutic strategy for AS, in this study, we conclude that the local injection of AMSCs is more appropriate than BMSCs to treat AS.

Protective Effects of 5-HT1A Receptor Inhibition and 5-HT2A Receptor Stimulation Against Streptozotocin-Induced Apoptosis in the Hippocampus.

INTRODUCTION: Intracerebroventricular administration of streptozotocin (icv-STZ) induced apoptosis changes in neurons similar to Alzheimer's disease. The serotonergic system via its receptor involved in survival of neurons. The present study examined the ability of selective 5-HT1A receptor antagonist (NAD-299) and 5-HT2A receptor agonist (TCB-2) to attenuate the apoptosis caused by the icv-STZ in the rat. METHODS: The icv-STZ (3 mg/kg, 10 µL, twice) induced neuronal loss in the hippocampus of adult male rats. Animals were divided into naive control, sham-operated, STZ+saline (1 µL, icv), STZ+NAD-299 (5 µg/µL, icv), STZ+TCB-2 (5 µg/µL, icv), and STZ+NAD-299+TCB-2 (5 µg/µL of any agent, icv) groups. Following the 35 days' treatment period, neuronal apoptosis was detected using the Tunnel. Cells with morphological features of apoptotic cell were contended by microscopy. RESULTS: TCB-2 and NAD-299 administration decreased number of apoptotic neurons in the treatment group compared with the STZ group. Combined treatment of STZ rat with NAD+TCB more decreased number of apoptotic cells in compare to TCB-2 or NAD-299 treated STZ groups. CONCLUSION: Treatment with 5-HT1A receptor antagonist or 5-HT2A receptor agonist diminished apoptosis. The beneficial effect of 5HT1A receptor inhibition was potentiated with activation of 5-HT2A receptor in prevention of apoptosis in hippocampus.

Improved antibacterial function of Rifampicin-loaded solid lipid nanoparticles on Brucella abortus.

The objective of this study was to assess the antibacterial activity of Rifampicin-loaded solid lipid nanoparticles on Brucella abortus 544. Rifampicin-loaded solid lipid nanoparticles were prepared by a modified microemulsion/sonication method and characterized. The results showed the average size about 319.7 nm, PI about 0.20 and zeta potential about 18.4 mv, encapsulation efficacy and drug-loading were equal to 95.78 and 34.2%, respectively, with a spherical shape. Drug release lasted for 5 days. The antibacterial activity was statistically significant with p < .05 in bacterial and cell culture media compared to free Rifampicin. It can be concluded that solid lipid nanoparticles can be considered as a promising delivery system for improving the antibacterial activity of Rifampicin against Brucella abortus.