Search

Purpose Lanthanum oxide (La2O3) nanoparticles (NPs) have been widely used in catalytic and photoelectric applications , but the reproductive toxicity is still unclear. This study evaluated the reproductive toxicity of two different-sized La2O3 particles in the testes. Materials and methods Fifty Kunming mice were randomly divided into five groups. Mice were treated with La2O3 NPs by repeated intragastric administration for 90 days (control, nano-sized with 5, 10, 50 mg/ kg BW and micro-sized with 50 mg/ kg BW). Mice in the control group were treated with de-ionised water without La2O3 NPs. Sperm parameters, testicular histopathology, TEM assessment, hormone assay and nuclear factor erythroid 2-related factor 2 (Nrf-2) pathway were performed and evaluated. Results The body weight of mice treated with La2O3 NPs or not had no difference; sperm parameters and histological assessment showed that La2O3 NPs could induce reproductive toxicity in the testicle. Serum testosterone and gonadotropin-releasing hormone (GnRH) in the NH (nano-sized with 50 mg/ kg BW) group were markedly decreased relative to control group, and an increase of luteinizing hormone (LH) in NH group was detected . Additionally, transmission electron microscopy revealed that the ultrastructural abnormalities induced by La2O3 NPs were more severe than La2O3 MPs in the testes. Furthermore, La2O3 NPs treatment inhibited the translocation of nuclear factor erythroid 2-related factor 2 (Nrf-2) from the cytoplasm into the nucleus as well as the expression of downstream genes NAD(P)H quinone oxidoreductase1 (NQO1), hemeoxygenase 1 (HO-1) and ( glutathione peroxidase) GSH-Px, thus abrogating Nrf-2-mediated defense mechanisms against oxidative stress. Conclusions The results of this study demonstrated that La2O3 NPs improved the spermatogenesis defects in mice. La2O3 NPs inhibited Nrf-2/ARE signaling pathway that resulted in apoptosis in the mice testes.

Lanthanum oxide (La2O3) nanoparticles (NPs) have been widely used in photoelectric and catalytic applications. However, their exposure and reproductive toxicity is unknown. In this study, the effect of the intragastric administration of two different-sized La2O3 particles in the testes of mice for 60 days was investigated. Although the body weight of mice treated or not treated with La2O3 NPs was not different and La2O3 NPs were distributed in the organs including the testis, liver, kidney, spleen, heart and brain. La2O3 NPs accumulate more than micro-sized La2O3 (MPs) in mice testes. The histopathological evaluation showed that moderate reproductive toxicity induced by La2O3 NPs in the testicle tissues. Furthermore, increased MDA, 8-OHdG levels and decreased SOD activities were detected in the La2O3 NP-treated groups. Moreover, qRT-PCR and western blotting data indicated that La2O3 NPs affecting the blood-testis barrier (BTB)-related genes in mice testes. Taken together, these findings suggested that La2O3 NPs activated inflammation responses and cross the BTB in the murine testes. This study provided useful information for risk analysis and regulation of La2O3 NPs by administrative agencies.

The hypothesis that omega-3 fatty acids may play a role in preventing and treating depression is based on correlative associations between fish consumption, omega-3 fatty acid intake and the prevalence of major depressive disorder. Reduced omega-3 fatty acid erythrocyte levels have been found in individuals with depressive disorders. These observational findings are unable to establish a causal relationship between omega-3 fatty acids and depression. The results of randomized controlled trials of omega-3 fatty acids for depressive disorders are inconclusive and also fail to prove causation. The therapeutic efficacy of omega-3 fatty acids appears to be moderate at best but is more likely to be minimal or non-existent. Potential long-term adverse effects of omega-3 fatty acid supplementation should be considered. Large-scale, well-controlled clinical trials are required to establish potential anti-depressive effects of omega-3 fatty acids. Such studies need to consider baseline values of omega-3 fatty acids and symptom severity, the dosage and types of the fatty acids used, the duration of supplementation and the concomitant use of medication. Conclusive evidence of the efficacy of omega-3 fatty acids in depression is currently lacking. The recommendation of potentially ineffective therapies may have considerable opportunity costs, with other possibly more useful treatments remaining unutilized.

Lanthanum oxide (La

The reproductive toxicity of SnS

Lanthanum oxide nanoparticles (La

SnS2 nanoflowers (SnS2 NFs) have been widely used in photoelectric and catalytic applications. However, its explosure and reproductive toxicity is unknown. The aim of this study was to investigate the effect of exposure to 3 different sized-SnS2 flowers (dose: 38 mg/kg; size: 50, 80, and 200 nm) in testes of mice for 4 weeks by intraperitoneal injection. Though the body weight of mice treated or not with SnS2 NFs was not different, and SnS2 NFs were distributed to the organs including liver, kidney, spleen, heart, brain, and testis, more distribution SnS2 NFs (50 and 80 nm) were found in testicle tissues compared with SnS2 flowers (200 nm) in those tissues. The results of sperm count and survival analysis, histopathological evaluation, and qRT-PCR detection showed that there was moderate reproductive toxicity induced by the small-sized SnS2 NFs in testicle tissues. Furthermore, elevated malondialdehyde level and decreased superoxide dismutase activity were also observed in the SnS2 NFs (dose: 38 mg/kg; size: 50 and 80 nm) treated groups. Likewise, the qRT-PCR data indicated that SnS2 NFs can induce apoptosis and inflammation responses. Although the pro-inflammation marker of TNF-α, IL-1β, iNOS, and COX-2 at the mRNA levels were higher expression in 50 and 80 nm groups than that in control and 200 nm group, no statistical significance existed between 50 and 80 nm groups. Accordingly, the repeated-dose toxicity of SnS2 NFs in testicle tissues was also observed in a dose-dependent manner by intraperitoneal injection of SnS2 NFs (size: 50 nm; 0.38, 3.8, and 38 mg/kg) for 4 weeks, when determined by sperm count, survival rate, and qRT-PCR analysis. In addition, transmission electron microscopy showed that the ultrastructural abnormalities formed by the small-sized SnS2 NFs in testes were more severe than those formed by the large-sized SnS2 in testes. Taken together, these findings implied that the SnS2 NFs activated inflammation responses that signified apoptosis in murine testes. This study provided useful information for risk analysis and regulation of SnS2 NFs by administration agencies.

Rationale: Abdominal aortic aneurysms (AAAs) are characterized by pathological remodeling of the aortic wall. Although both increased Krüppel-like factor 5 (KLF5) expression and macrophage infiltration have been implicated in vascular remodeling, the role of KLF5 in macrophage infiltration and AAA formation remains unclear. Objective: To determine the role of KLF5 in AAA formation and macrophage infiltration into AAAs. Methods and Results: KLF5 expression was significantly increased in human AAA tissues and in 2 mouse models of experimental AAA. Moreover, in myeloid-specific Klf5 knockout mice (myeKlf5 −/− mice), macrophage infiltration, medial smooth muscle cell loss, elastin degradation, and AAA formation were markedly decreased. In cell migration and time-lapse imaging analyses, the migration of murine myeKlf5 −/− macrophages was impaired, and in luciferase reporter assays, KLF5 activated Myo9b (myosin IXB) transcription by direct binding to the Myo9b promoter. In subsequent coimmunostaining studies, Myo9b was colocalized with filamentous actin, cortactin, vinculin, and Tks5 in the podosomes of phorbol 12,13-dibutyrate–treated macrophages, indicating that Myo9b participates in podosome formation. Gain- and loss-of-function experiments showed that KLF5 promoted podosome formation in macrophages by upregulating Myo9b expression. Furthermore, RhoA-GTP levels increased after KLF5 knockdown in macrophages, suggesting that KLF5 lies upstream of RhoA signaling. Finally, Myo9b expression was increased in human AAA tissues, located in macrophages, and positively correlated with AAA size. Conclusions: These data are the first to indicate that KLF5-dependent regulation of Myo9b/RhoA is required for podosome formation and macrophage migration during AAA formation, warranting consideration of the KLF5–Myo9b–RhoA pathway as a therapeutic target for AAA treatment.

KLF5 and nuclear factor κB (NF-κB) regulate cell proliferation and inflammation. Vitamin D signaling through vitamin D receptor (VDR) exerts anti-proliferative and anti-inflammatory actions. However, an actual relationship between KLF5, NF-κB and VDR in the inflammation and proliferation of macrophages is still unclear. Here, we showed that LPS and proinflammatory cytokines stimulate KLF5 gene expression in macrophages, and that 1, 25(OH)2D3 suppresses LPS-induced KLF5 expression and cell proliferation via upregulation of VDR expression. Mechanistic studies suggested that KLF5 interacts with p50 subunit of NF-κB to cooperatively induce the expressions of positive cell cycle regulators cyclin B1 and Cdk1/Cdc2 in LPS-treated macrophages. Further studies revealed that 1, 25(OH)2D3-induced interaction of VDR with p50 decreases LPS-induced interaction of KLF5 with p50. Collectively, we identify a novel regulatory pathway in which 1, 25(OH)2D3 induces VDR expression and promotes VDR interaction with p50 subunit of NF-κB, which in turn attenuates the association of KLF5 with p50 subunit of NF-κB and thus exerts anti-inflammatory and anti-proliferative effects on macrophages.

Purpose Lanthanum oxide (La2O3) nanoparticles (NPs) have been widely used in catalytic and photoelectric applications , but the reproductive toxicity is still unclear. This study evaluated the reproductive toxicity of two different-sized La2O3 particles in the testes. Materials and Methods Fifty Kunming mice were randomly divided into five groups. Mice were treated with La2O3 NPs by repeated intragastric administration for 90 days (control, nano-sized with 5, 10, 50 mg/ kg BW and micro-sized with 50 mg/ kg BW). Mice in the control group were treated with de-ionised water without La2O3 NPs. Sperm parameters, testicular histopathology, TEM assessment, hormone assay and nuclear factor erythroid 2-related factor 2 (Nrf-2) pathway were performed and evaluated. Results The body weight of mice treated with La2O3 NPs or not had no difference; sperm parameters and histological assessment showed that La2O3 NPs could induce reproductive toxicity in the testicle. Serum testosterone and gonadotropin-releasing hormone (GnRH) in the NH (nano-sized with 50 mg/ kg BW) group were markedly decreased relative to control group, and an increase of luteinizing hormone (LH) in NH group was detected . Additionally, transmission electron microscopy revealed that the ultrastructural abnormalities induced by La2O3 NPs were more severe than La2O3 MPs in the testes. Furthermore, La2O3 NPs treatment inhibited the translocation of nuclear factor erythroid 2-related factor 2 (Nrf-2) from the cytoplasm into the nucleus as well as the expression of downstream genes NAD(P)H quinone oxidoreductase1 (NQO1), hemeoxygenase 1 (HO-1) and ( glutathione peroxidase) GSH-Px, thus abrogating Nrf-2-mediated defense mechanisms against oxidative stress. Conclusions The results of this study demonstrated that La2O3 NPs improved the spermatogenesis defects in mice. La2O3 NPs inhibited Nrf-2/ARE signaling pathway that resulted in apoptosis in the mice testes.

Lanthanum oxide nanoparticles (La2O3 NPs) are used in photoelectric and catalytic applications. Astaxanthin (ASX) is a red carotenoid pigment with antioxidant and anti-inflammatory properties, and the antioxidant activities promote neuroprotection. This study explored the effect of ASX supplementation on La2O3 NP-induced neurotoxicity in mice and the molecular mechanisms of such protective effects. Amongst our findings, we determined that ASX treatment significantly attenuated La2O3 NP-induced behavioural abnormalities, histopathological evidence of hippocampal injury and ultrastructural changes in the CA1 region of the hippocampus. ASX treatment also markedly inhibited the production of ROS and activated PI3K/AKT signaling, which facilitated the nuclear translocation of Nrf-2 and reversed the down-regulation of HO-1, NQO1 and GCLM proteins in the hippocampus that were induced by sub-chronic exposure to La2O3 NPs. Administration of ASX to mice receiving La2O3 NPs also resulted in decreased expression of iNOS, IL-1β, TNF-α, COX-2, Bax and Caspase-3 and in increased expression of BDNF, NGF and Bcl-2 observed in response to La2O3 NPs. In conclusion, ASX had a markedly protective effect against the negative sequelae associated with La2O3 NP-induced neurotoxicity. This may result from the activation of the PI3K/AKT/Nrf-2 signaling and via the inhibition of oxidative stress, neuroinflammation and cellular apoptosis.

Tin sulfide (SnS2) nanoflowers (NFs) with highly photocatalytic activity for wastewater treatment may lead to potential health hazards via oral routes of human exposure. No studies have reported the hepatic effects of SnS2 NFs on the metabolic function and hepatotoxicity. In this study, we examined the hepatic effects of the oral administration of SnS2 NFs (250-1000 mg/kg) to ICR mice for 14 days, with the particle size ranging from 50 to 200 nm. Serum and liver tissue samples were assayed using biochemical analysis, liver histopathology and metabolic gene expression. The different sizes of SnS2 NFs (250 mg/kg dose), such as 50, 80, and 200 nm, did not induce any adverse hepatic effect related to biochemical parameters or histopathology in the treated mice compared with controls. The oral administration of 50-nm SnS2 NFs at doses of 250, 500, and 1000 mg/kg for 14 days produced dose-dependent hepatotoxicity and inflammatory responses in treated mice. Furthermore, the expression of metabolic genes in the liver tissues was altered, supporting the SnS2 NF-related hepatotoxic phenotype. The oral administration of SnS2 NFs also produced abnormal microstructures in the livers of the treated mice. Taken together, these data indicate that the increased risk of hepatotoxicity in SnS2 NF-treated mice was independent of the particle size but was dependent on their dose. The no-observed-adverse effect level was

KLF5 and nuclear factor κB (NF-κB) regulate cell proliferation and inflammation. Vitamin D signaling through vitamin D receptor (VDR) exerts anti-proliferative and anti-inflammatory actions. However, an actual relationship between KLF5, NF-κB and VDR in the inflammation and proliferation of macrophages is still unclear. Here, we showed that LPS and proinflammatory cytokines stimulate KLF5 gene expression in macrophages, and that 1, 25(OH)