Associations of anxiety and depression with restless leg syndrome: a systematic review and meta-analysis.

Background: The levels of anxiety and depression among patients with restless leg syndrome (RLS) are controversial. The aim of this systematic review and meta-analysis was to compare the levels of depression and anxiety among individuals with RLS with those of healthy controls. Methods: We conducted an extensive electronic search of the PubMed, Web of Science, EMBASE, and Cochrane Library databases from their inception dates to 20 June 2023. Studies presenting data on depression and anxiety in individuals with RLS were included, and a comprehensive meta-analysis was performed. Results: Twenty-one studies matched the inclusion criteria. Significantly more depressive symptoms were present in the individuals with RLS than in those without RLS, as measured by the Beck Depression Inventory [mean difference (MD) = 6.58, 95% confidence interval (CI) = 5.54-7.62, p < 0.01; heterogeneity I2 = 0%, p = 0.99]. Similarly, the results from the Beck Anxiety Inventory indicated that there were significantly more pronounced anxiety symptoms in the individuals with RLS than in those without RLS (MD = 9.30, 95%CI = 7.65-10.94, p < 0.01; heterogeneity I2 = 0%, p = 0.92). The other anxiety and depression scales also yielded statistically significant results. Significant heterogeneity was observed in the Hamilton Depression Rating Scale and Hamilton Anxiety Rating Scale, with the primary contributing factor probably being the scoring criteria of the scales. Conclusion: This meta-analysis found that the levels of depression and anxiety symptoms were significantly higher in individuals with RLS than in their healthy counterparts.Systematic review registration:https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023410364, (identifier CRD42023410364).

Soy isoflavones ameliorate the cognitive dysfunction of Goto-Kakizaki rats by activating the Nrf2-HO-1 signalling pathway.

Soy isoflavones (SIF) are soybean phytochemicals that are considered to be biologically active components that protect from neurodegenerative diseases. In this study, the therapeutic effect of SIF was evaluated in a diabetic Goto-Kakizaki (GK) rat model. Twenty male GK rats were randomly divided into diabetes mellitus (DM) model group and SIF+DM group (n=10 in each group). Twenty age-matched male Wistar rats were randomly divided into control group (CON group) and CON+SIF group, with 10 rats in each group. The learning and memory functions of the animals were determined by the Morris water maze (MWM) test. Hematoxylin-eosin staining (HE) was performed to examine pyramidal neuron loss in the CA1 area of the hippocampus. Markers of oxidative stress (OS) were measured to evaluate oxidative stress-mediated injury. RT-PCR and western blotting were used to analyze the expression of nuclear factorerythroid2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1) and NAD(P)H dehydrogenase quinone1 (NQO1). Treatment with SIF for 4 weeks alleviated the cognitive dysfunction of the GK rats as determined by the MWM test. Moreover, SIF treatment also reduced diabetes-related oxidative reactions. In addition, SIF enhanced the expression of Nrf2, HO-1 and NQO1, suggesting a potential antioxidation mechanism for the effect of SIF. These findings suggest that SIF can be considered candidates for inhibiting the progression of diabetes-induced cognitive dysfunction, provide novel insights into the antioxidant effect of SIF and further strengthen the link between oxidative stress and diabetes.

Protective effect of astaxanthin against SnS2 nanoflowers induced testes toxicity by suppressing RIPK1-RIPK3-MLKL signaling in mice.

The reproductive toxicity of SnS2 nanoflowers (SnS2 NFs) has been studied in our previous experiment, but the underlying mechanism is still not clear. Astaxanthin (ASX) is a red carotenoid pigment with antioxidant, anticancer and anti-inflammatory properties, showing neuroprotective properties via its antioxidant capacity. To examine the ASX effect on sub-chronic testis injury induced by SnS2 NFs, we randomly and equally divided 40 Kunming male mice into four groups (control, ASX control, NF and NF + ASX groups). Then, ASX dissolved in olive oil was administered intragastrically for 30 consecutive days. Results showed that ASX treatment improved the sperm parameters in mice. Meanwhile, the ASX treatment significantly attenuated testis histopathological injury and ultrastructure alterations induced by SnS2 NFs. It also alleviated testicular oxidative stress, inflammation, apoptosis and necroptosis in mice. Furthermore, ASX markedly upregulated the expression of Bcl-2 and downregulated the expressions of Fas, FasL, RIPK1, FADD, Bax, Cytochrome C, Caspase-9, Cleaved Caspase-8, Cleaved Caspase-3, RIPK3, MLKL and FLIP in the testis tissues compared with the NF group. Therefore, ASX had a markedly protective effect against SnS2 NFs in mice, and the potential mechanism is associated with its ability to inhibit the oxidative stress, inflammatory response, testicular apoptosis and necroptosis, as well as downregulating in the expression of the RIPK1-RIPK3-MLKL signaling and mitochondrial related apoptosis genes.

Effects of intragastric administration of La2O3 nanoparticles on mouse 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.

Protective effect of astaxanthin against La2O3 nanoparticles induced neurotoxicity by activating PI3K/AKT/Nrf-2 signaling in mice.

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-1ß, 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.

La2O3 Nanoparticles Induce Reproductive Toxicity Mediated by the Nrf-2/ARE Signaling Pathway in Kunming Mice.

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.

Identification and functional analysis of a novel splice variant of AC3-33 in breast cancer.

Alternative RNA splicing plays a key role in regulating gene function and influencing protein expression diversity. In the present study, an AC-33 transcript variant (NCBI Reference Sequence: NM_001308229.1), splice variant (sv)AC3-33, was successfully cloned from the MCF-7 breast cancer cell line by reverse transcription PCR using primers based on expressed sequence tags. The aim of the present study was to investigate the structure and function of svAC3-33. svAC3-33 has an open reading frame of 1,825 base pairs, lacks AC3-33 exon 2 and is encoded by 294 amino acids. svAC3-33 is localized within the cytoplasm. The Cell Counting Kit-8 and EdU detection of cell proliferation assays showed that svAC3-33 inhibited MCF-7 cell proliferation. Similarly, svAC3-33 knockdown by RNA interference was shown to have the opposite effect by repressing the cell cycle progression of breast cancer cells. Furthermore, the data indicated that svAC3-33 may upregulate the expression of p21. The present study provides evidence that the increased expression of svAC3-33 may inhibit the activity of the transcription factor AP-1. The luciferase reporter gene assay detected a downregulation of the expression of c-Jun, but not c-Fos, which in turn affected cell proliferation. In conclusion, these results indicated a function for svAC3-33 in inhibiting the cell proliferation of MCF-7 cells by regulating the AP-1 signaling pathway.