Synthesis, characterization and hepatoprotective effect of silymarin phytosome nanoparticles on ethanol-induced hepatotoxicity in rats.

Introduction: Silymarin proved to be a beneficial herbal medicine against many hepatic disorders such as alcoholic liver disease (ALD). However, its application is restricted due to its low bioavailability and consequently decreased efficacy. We herein used a nano-based approach known as "phytosome", to improve silymarin bioavailability and increase its efficacy. Methods: Phytosome nanoparticles (NPs) were synthesized using thin film hydration method. NPs size, electrical charge, morphology, stability, molecular interaction, entrapment efficiency (EE %) and loading capacity (LC %) were determined. Moreover, in vitro toxicity of NPs was investigated on mesenchymal stem cells (MSCs) viability using MTT assay. In vivo experiments were performed using 24 adult rats that were divided into four groups including control, ethanol (EtOH) treatment, silymarin/EtOH treatment and silymarin phytosome/EtOH, with 6 mice in each group. Experimental groups were given 40% EtOH, silymarin (50 mg/kg) and silymarin phytosome (200 mg/kg) through the gastric gavage once a day for 3 weeks. Biochemical parameters, containing ALP, ALT, AST, GGT, GPx and MDA were measured before and after experiment to investigate the protective effect of silymarin and its phytosomal form. And histopathological examination was done to evaluate pathological changes. Results: Silymarin phytosome NPs with the mean size of 100 nm were produced and were well tolerated in cell culture. These NPs showed a considerable protective effect against ALD through inverting the biochemical parameters (ALP, ALT, AST, GGT, GPx) and histopathological alterations. Conclusion: Silymarin phytosomal NPs can be used as an efficient treatment for ALD.

Targeting long noncoding RNAs in neuroblastoma: Progress and prospects.

Neuroblastoma (NB) is the third most prevalent tumor that mostly influences infants and young children. Although different treatments have been developed for the treatment of NB, high-risk patients have been reported to have low survival rates. Currently, long noncoding RNAs (lncRNAs) have shown an attractive potential in cancer research and a party of investigations have been performed to understand mechanisms underlying tumor development through lncRNA dysregulation. Researchers have just newly initiated to exhibit the involvement of lncRNAs in NB pathogenesis. In this review article, we tried to clarify the point we stand with respect to the involvement of lncRNAs in NB. Moreover, implications for the pathologic roles of lncRNAs in the development of NB have been discussed. It seems that some of these lncRNAs have promising potential to be applied as biomarkers for NB prognosis and treatment.

Global epidemiology of HBV infection among hemodialysis patients: A systematic review and meta-analysis.

BACKGROUND & AIMS: Hemodialysis (HD) is a life-saving procedure that purifies the blood in patients with end-stage renal disease (ESRD). Among all major complications, blood-borne diseases like hepatitis B virus (HBV) may be exposed as serious side effects of hemodialysis. A comprehensive review of the global burden of HBV among HD patients has not been written so far. The aim of the current systematic review and meta-analysis was to determine the globally epidemiology of HBV infection among HD patients. METHODS: Based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, articles that investigated the prevalence of HBV among HD patients were searched from the major databases such as EMBASE, PubMed, Web of Science collection, and Scopus. Pooled prevalence with 95% CI and identification of heterogeneity were obtained using the random effects model and Cochran's Q-test, respectively, and quantification was evaluated using the I2 statistics. All statistical analyses were performed by STATA 14.1 statistical software. RESULTS: among 322 datasets (795,623 cases) that included in this study, the pooled prevalence of HBV infection among HD patients was 7.32% (95% CI: 6.53-8.15%; I2 = 97.91%), including 7.57% (95% CI: 6.69-8.48%) for HBsAg and 6.09% (95% CI: 4.05-8.49%) for DNA, respectively. In addition, based on geographic area, the prevalence was 7.44% (95% CI: 6.35-8.61%) in Asia, 4.32% (95% CI: 2.21-7.04%) in North America, 7.07% (95% CI: 6.35-8.61%) in Europe, 5.52% (95% CI: 3.60-7.78%) in Africa, 8.45% (95% CI: 5.81-11.78%) in Oceania, and 9.73% (95% CI: 7.11-12.70%) in South America. CONCLUSIONS: Our analysis indicates a relatively high prevalence of HBV infection in HD patients, even in some developed countries. Considering that ESRD patients are not able to properly respond to the vaccination strategies in order to develop an acceptable immunity, vaccination of healthy individuals is highly recommended to arm their bodies for possible immunocompromise conditions in the future. Moreover, donated blood in blood transfusion centers should be checked for possible hepatitis B virus infection using sensitive molecular tests.

Exosome-based strategies for diagnosis and therapy of glioma cancer.

Glioblastoma belongs to the most aggressive type of cancer with a low survival rate that is characterized by the ability in forming a highly immunosuppressive tumor microenvironment. Intercellular communication are created via exosomes in the tumor microenvironment through the transport of various biomolecules. They are primarily involved in tumor growth, differentiation, metastasis, and chemotherapy or radiation resistance. Recently several studies have highlighted the critical role of tumor-derived exosomes against immune cells. According to the structural and functional properties, exosomes could be essential instruments to gain a better molecular mechanism for tumor understanding. Additionally, they are qualified as diagnostic/prognostic markers and therapeutic tools for specific targeting of invasive tumor cells such as glioblastomas. Due to the strong dependency of exosome features on the original cells and their developmental status, it is essential to review their critical modulating molecules, clinical relevance to glioma, and associated signaling pathways. This review is a non-clinical study, as the possible role of exosomes and exosomal microRNAs in glioma cancer are reported. In addition, their content to overcome cancer resistance and their potential as diagnostic biomarkers are analyzed.

Anti-inflammatory and antioxidant effects of astaxanthin following spinal cord injury in a rat animal model.

Spinal cord injury (SCI) is a severely debilitating problem leading to substantial decrease in the quality of life. After spinal cord injury, inflammation and oxidative stress plays a key role in initiating the secondary injury cascades leading to progressive tissue degradation and extreme functional deficits. Given that the primary mechanical injuries to spinal cord are rarely repaired, the pharmacological interventions may improve the neurological outcomes caused by secondary injury. Astaxanthin (AST) is considered as a xanthophyll carotenoid with potent antioxidant and anti-inflammatory properties, which has various pharmacological activities. In the present study, we aimed to firstly assess the protective effect of AST, and then to define the AST mechanism of action on a rat model of SCI. Based on the results of von Frey test, AST treatment significantly alleviated the SCI-induced neuropathic pain compared with the control groups (P < 0.05). The expression analysis by western blot shows reduced expression levels of COX-2, TNF-α, IL-1ß, and IL-6 following AST treatment (P < 0.05). The activity of antioxidant enzymes was evaluated using ELISA. Therefore, ELISA experiments showed a significant reduction in the level of oxidative stress in SCI rat following AST treatment (P < 0.05). Furthermore, histopathological evaluations revealed that myelinated white matter and motor neuron number were significantly preserved after treatment with AST (P < 0.05). In conclusion, our study shows that AST could improve SCI through anti-inflammatory and antioxidant effects which leads to decreased tissue damage and mechanical pain after SCI.

Dietary Patterns and Risk of Invasive Ductal and Lobular Breast Carcinomas: A Systematic Review and Meta-analysis.

The histopathologic subtypes of breast cancer, including invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC), differ in terms of risk factors, progression, and response to treatment. The PubMed/Medline, Web of Science, and Scopus databases were searched up to February 2020 for published studies on the association between dietary patterns (Western diet [WD] or Mediterranean diet [WD]) and the risk of IDC/ILC of breast. Multivariable adjusted relative risk (RR) and 95% confidence intervals (CIs) comparing the highest and lowest categories of WD and MD patterns were combined by using the random-effects meta-analyses. After searching the databases, 10 eligible studies on the association of diet and IDC (7 articles) and ILC (3 articles) were included in the analysis. A statistically significant adverse association was observed between MD and IDC in case-control studies (RR = 0.47; 95% CI, 0.39-0.55; I2 = 85.1%; P < .001). However, the association was nonsignificant in cohort studies (RR = 0.98; 95% CI, 0.92-1.05; I2 = 88.8%; P = .003). The pooled analysis also suggested a significant and direct association between the WD and the risk of IDC (RR = 1.36; 95% CI, 1.18-1.53; I2 = 63.7%; P = .017). The risk of ILC for the highest compared to the lowest category of MD was highly protective (RR = 0.76; 95% CI, 0.64-0.87; I2 = 89.2%; P < .001), and a marginally significant association was found between the WD and risk of ILC (RR = 1.45; 95% CI, 1.04-1.86), with no heterogeneity (I2 = 0; P = .52). This meta-analysis provides supporting evidence for the association between MD decreased risk of IDC and ILC of the breast and the association between WD and increased risk of IDC and ILC. Further investigations are needed to better understand the reasons behind the etiologic mechanisms of how dietary patterns affect patients differently by common breast cancer subtypes, including IDC and ILC.

Nanoparticles and Vaccine Development.

In spite of the progress of conventional vaccines, improvements are required due to concerns about the low immunogenicity of the toxicity, instability, and the need for multiple administrations of the vaccines. To overcome the mentioned problems, nanotechnology has recently been incorporated into vaccine development. Nanotechnology increasingly plays an important role in vaccine development nanocarrier-based delivery systems that offer an opportunity to increase the cellular and humoral immune responses. The use of nanoparticles in vaccine formulations allows not only enhanced immunogenicity and stability of antigen, but also targeted delivery and slow release. Over the past decade, nanoscale size materials such as virus-like particles, liposomes, ISCOMs, polymeric, inorganic nanoparticles and emulsions have gained attention as potential delivery vehicles for vaccine antigens, which can both stabilize vaccine antigens and act as adjuvants. This advantage is attributable to the nanoscale particle size, which facilitates uptake by Antigen- Presenting Cells (APCs), then leading to efficient antigen recognition and presentation. Modifying the surfaces of nanoparticles with different targeting moieties permits the delivery of antigens to specific receptors on the cell surface, thereby stimulating selective and specific immune responses. This review provides an overview of recent advances in nanovaccinology.

Role of L-arginine/NO/cGMP/KATP channel signaling pathway in the central and peripheral antinociceptive effect of thymoquinone in rats.

OBJECTIVES: Growing evidence demonstrates that L-arginine/NO/cGMP/KATP channel pathway has a modulatory role in pain perception. Previous studies have shown that thymoquinone exerts antinociceptive effects; however, the mechanisms underlying antinociception induced by thymoquinone have not been fully clarified. The aim of the present study was to evaluate the role of L-arginine/NO/cGMP/KATP channel pathway in the central and peripheral antinociceptive effect of thymoquinone in rats. MATERIALS AND METHODS: Rats were pretreated intraplantarly (IPL) or intracerebroventricularly (ICV) with L-arginine (the NO precursor), l-NAME (an NO synthase inhibitor), SNAP (an NO donor), methylene blue (a guanylyl cyclase inhibitor), glibenclamide (the blocker of KATP channel), and tetraethylammonium (TEA, a Kv channel blocker) before the injection of thymoquinone. RESULTS: Local ipsilateral (20 and 40 µg, IPL) but not contralateral and ICV (4 and 8 µg) administration of thymoquinone caused a dose-dependent and significant antinociception in both early and late phases of the formalin test. Pretreatment of rats with L-arginine (100 µg, IPL or ICV) and SNAP (200 µg, IPL or ICV) increased while l-NAME (100 µg, IPL or 1 µg, ICV) and methylene blue (400 µg, IPL or ICV) decreased the antinociceptive effects of thymoquinone in the formalin test. The administration of TEA (IPL or ICV) did not modify but glibenclamide (50 µg, IPL or ICV) significantly abolished the peripheral and central antinociceptive effects of thymoquinone in both phases of the formalin test. CONCLUSION: The results of the present study indicate that L-arginine/NO/cGMP/KATP channel pathway participates in the central and peripheral antinociceptive effect of thymoquinone.

Neuroprotective effects of astaxanthin in a rat model of spinal cord injury.

Spinal cord injury (SCI) often leads to constant neurological deficits and long-term unalterable disability. Apoptosis plays an important role in the initiation of the secondary injury cascades leading to progressive tissue damage and severely functional deficits after SCI. Although the primary mechanical destructive events cannot be reversed, a therapeutic intervention could be carried out in order to moderate the secondary injury damage several hours to weeks after injury. Astaxanthin (AST) is a strong antioxidant and anti-inflammatory agents with the potential to render anti-apoptotic and neuroprotective effects. In the current study, we examined the therapeutic potential of AST on adult rats after severe SCI contusion. Results of BBB scores showed that AST improved motor function after SCI compared to control groups. Western blot analysis showed reduced expression of Bax and Cleaved-caspase-3 proteins and increased expression of the Bcl-2 protein in response to AST treatment (p<0.05). The histology results also showed that AST considerably preserved myelinated white matter and the number of motor neurons. This study is the first to report that AST reduces neuronal apoptosis, diminishes pathological tissue damage and improves functional recovery after SCI. The observed prominent neuroprotective effects, introduces AST as a promising therapy for SCI.

Relationship between religion and school students' road behavior in southern Iran.

PURPOSE: Unsafe behaviors are an important cause of accidents in adolescent age groups. This study was designed to examine the behaviors of adolescent pedestrians in southern Iran. METHODS: This is a descriptive analytical cross-sectional study. The study population consisted of high school students in Shiraz, capital city of Fars Province, Iran. Five hundred and sixteen students were selected by multi-stage sampling. Data were collected by the use of three questionnaires, which included Persian copies of adolescent road user behavior questionnaire (ARBQ), Duke University Religious Index (DUREL), as well as the context and independent variables questionnaire. RESULTS: The results showed that a decrease in dangerous behaviors on the road resulted in an increase in respondents' intrinsic religiosity. Also, engagement in unsafe crossing behavior in the road decreased with increasing respondents' intrinsic religiosity. Another finding showed that female students were less involved in dangerous play and planned protective behaviors on the road. CONCLUSION: Findings clearly indicate that intrinsic religiosity has a significant role in reducing the risky road behaviors of students. Hence, religion may improve road safety in school students' road behavior in Iran.

Attenuation of morphine tolerance and dependence by thymoquinone in mice.

OBJECTIVE: Dependence and tolerance are major restricting factors in the clinical use of opioid analgesics. In the present study, the effects of thymoquinone, the major constituent of Nigella sativa seeds, on morphine dependence and tolerance were investigated in mice. MATERIALS AND METHODS: Male adult NMRI mice were made tolerant and dependent by repeated injections of morphine (50, 50, and 75 mg/kg, i.p. on 9 a.m., 1 p.m., and 5 p.m., respectively) during a 3-day administration schedule. The hot-plate test was used to assess tolerance to the analgesic effects of morphine. Naloxone (2 mg/kg, i.p.) was injected to precipitate withdrawal syndrome in order to assess the morphine dependence. To evaluate the effects of thymoquinone on tolerance and dependence to morphine, different single or repeated doses of thymoquinone were administered in mice. Rotarod was used to assess the motor coordination. RESULTS: Administration of single or repeated doses of thymoquinone (20 and 40 mg/kg, i.p.) significantly decreased the number of jumps in morphine dependent animals. Repeated administration of thymoquinone (20 and 40 mg/kg, for 3 days) and also single injection of thymoquinone (40 mg/kg, on the fourth day) attenuated tolerance to the analgesic effect of morphine. None of the thymoquinone doses (10, 20, and 40 mg/kg) produced any antinociceptive effects on their own. Motor coordination of animals was impaired by the high dose of thymoquinone (40 mg/kg). CONCLUSION: Based on these results, it can be concluded that thymoquinone prevents the development of tolerance and dependence to morphine.

α-Terpineol attenuates morphine-induced physical dependence and tolerance in mice: role of nitric oxide.

OBJECTIVES: Dependence and tolerance to opioid analgesics are major problems limiting their clinical application. α-Terpineol is a monoterpenoid alcohol with neuroprotective effects which is found in several medicinal plants such as Myrtus communis, Laurus nobilis, and Stachys byzantina. It has been shown that some of these medicinal plants such as S. byzantina attenuate dependence and tolerance to morphine. Since α-terpineol is one of the bioactive phytochemical constituent of these medicinal plants, the present study was conducted to investigate the effects of α-terpineol on morphine-induced dependence and tolerance in mice. MATERIALS AND METHODS: The mice were rendered dependent or tolerant to morphine by a 3-day administration schedule. The hot-plate test and naloxone-induced withdrawal syndrome were used to evaluate tolerance and dependence on morphine, respectively. To investigate a possible role for nitric oxide (NO) in the protective effect of α-terpineol, the NO synthase inhibitor, L-N(G)-nitroarginine methyl ester (L-NAME) and NO precursor, L-arginine, were used. RESULTS: Administration of α-terpineol (5, 10, and 20 mg/kg, IP) significantly decreased the number of jumps in morphine dependent animals. Moreover, α-terpineol (20 and 40 mg/kg, IP) attenuated tolerance to the analgesic effect of morphine. The inhibitory effects of α-terpineol on morphine-induced dependence and tolerance were enhanced by pretreatment with L-NAME (10 mg/kg, IP). However, L-arginine (300 mg/kg, IP) antagonized the protective effects of α-terpineol on dependence and tolerance to morphine. CONCLUSION: These findings indicate that α-terpineol prevents the development of dependence and tolerance to morphine probably through the influence on NO production.

Lectin coated MgO nanoparticle: its toxicity, antileishmanial activity, and macrophage activation.

The purpose of this research was to evaluate toxicity of uncoated magnesium oxide nanoparticles (MgO NPs), MgO NPs coated with Peanut agglutinin (PNA) lectin, and PNA alone on the promastigotes of Leishmania major (L. major) and macrophages of BALB/c mice. On the other hand, antileishmanial property of uncoated MgO NPs, lectin coated MgO NPs, and PNA lectin alone was evaluated, and also macrophage activation was investigated after treatment with these materials by measurement of nitrite, H2O2, and some interleukins. This study showed that PNA lectin and lectin coated MgO NPs had approximately no toxicity on L. major and macrophages, but some toxic effects were observed for uncoated MgO NPs, especially at concentration of 500 µg/mL. Interestingly, lectin coated MgO NPs had the highest antileishmanial activity and macrophage activation, compared with uncoated MgO NPs and PNA lectin.

Silver and gold nanostructures: antifungal property of different shapes of these nanostructures on Candida species.

The shape of nanoparticles is an important determinant of their physical and chemical properties, possibly including the little-explored area of their use as antifungal agents. Therefore, we evaluated the in vitro antifungal activities of three different shapes of silver and gold nanostructures, including nanocubes, nanospheres, and nanowires, on Candida albicans, C. glabrata and C. tropicalis, using the microdilution and disk diffusion methods as per the guidelines of the Clinical and Laboratory Standards Institute. We found that silver and gold nanocubes had higher antifungal properties against the test species than nanospheres and nanowires. While some isolates were resistant to silver and gold nanospheres and nanowires, none of the isolates were resistant to silver and gold nanocubes. The occurrence of resistance is a new finding which should be further explored.