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Long-term exposure to high concentrations of fluoride (F) can damage mineralized and soft tissues such as bones, liver, kidney, intestine, and nervous system of adult rats. The high permeability of the blood-brain barrier and placenta to F during pregnancy and lactation may be critical to neurological development. Therefore, this study aimed to investigate the effects of F exposure during pregnancy and lactation on molecular processes and oxidative biochemistry of offspring rats' hippocampus. Pregnant Wistar rats were randomly assigned into 3 groups in accordance with the drinking water received G1 - deionized water (control); G2 - 10 mg/L of F and G3 - 50 mg/L of F. The exposure to fluoridated water began on the first day of pregnancy and lasted until the 21st day of breastfeeding (when the offspring rats were weaned). Blood plasma samples of the offspring rats were collected to determine F levels. Hippocampi samples were collected for oxidative biochemistry analyses through antioxidant capacity against peroxyl (ACAP), lipid peroxidation (LPO), and nitrite (NO2-) levels. Also, brain-derived neurotrophic factor (BDNF) gene expression (RT-qPCR) and proteomic profile analyses were performed. The results showed that exposure to both F concentrations during pregnancy and lactation increased the F bioavailability, triggered redox imbalance featured by a decrease of ACAP, increase of LPO and NO2- levels, BDNF overexpression and changes in the hippocampus proteome. These findings raise novel questions regarding potential repercussions on the hippocampus structure and functioning in the different cognitive domains.Environmental mercury is a concern for coastal ecosystem health, and exerts adverse effects on human health. Despite the growing body of evidence showing the hepatoprotective roles of curcumin on mercury, the knowledge between the macroscopic descriptions and the actual mechanism(s) underlying these processes is getting larger remains elusive. Herein, mice received single injection of mercuric chloride (HgCl2) (5 mg/kg body weight) and/or curcumin (50 mg/kg, body weight, p.o.). Firstly, the results showed curcumin could decline HgCl2-induced up-regulated the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Additionally, we also found that curcumin could suppress inflammatory damage, unbalance of trace elements (including sodium, magnesium, kalium, calcium overload), oxidative burst induced by HgCl2, which could be associated with cytochrome P450 (CYP450) signaling. Secondly, we found that curcumin could prevent HgCl2-induced cell death both in vivo and in vitro. Furthermore, curcumin significantly increased the nuclear translocation of nuclear factor E2-related factor 2 (Nrf2) and consequently upregulated the expression of heme oxygenase 1 (HO-1) under HgCl2 treatment. Meanwhile, inhibition of HO-1 by zinc protoporphyria could abolish the cytoprotective effects of curcumin in HgCl2-treated L02 hepatocytes. In conclusion, our data identify that curcumin could enhance Nrf2-mediated HO-1 to upregulate antioxidant ability, which might be associate with CYP450 signaling to suppress liver damage induced by HgCl2. The present study further enriches and perfects the mechanism theory of HgCl2 toxicity and suggest that the CYP450 signaling and Nrf2/HO-1 pathway is important in shedding light on curcumin's hepatoprotective effects in HgCl2 toxicity.Aggression and mental illness have been classically interlinked, often causing controversy and debate. Previous studies have shown that mental illness can be a risk factor to self- and other-directed aggression. However, these associations have rarely been simultaneously studied within the same population. Therefore, we aimed to study whether psychiatric disorders differentially increase the likelihood of one subtype of aggression over the other. We used the publicly available data of the National Survey on Drug Use and Health (NSDUH) from 2008 through 2014, for a total sample of 270,227 adult respondents. We designed our independent variable according to three categories no mental illness (NMI), low or moderate (LMMI) and serious (SMI). We constructed regression models to estimate the odds ratios for those having a mental illness committing (a) a subtype of aggression over the past year compared with no aggression and (b) other-directed compared to self-directed aggression. We found that most respondents with mental illness reported no past-year aggression of any type. However, respondents with mental illness had higher odds of perpetrating all subtypes of aggression. Additionally, respondents with LMMI and SMI were respectively 1.7 and 3 times more likely to engage in self- rather than other-directed aggression. Future research should focus on identifying accurate and reliable predictors of self- and other-directed aggression among individuals with mental illness.High-frequency transcranial random noise stimulation (hf-tRNS) is a non-invasive neuromodulatory technique capable of increasing human cortex excitability. HS94 cost There were only published case reports on the use of hf-tRNS targeting the lateral prefrontal cortex in treating negative symptoms of schizophrenia, thus necessitating systematic investigation. We designed a randomized, double-blind, sham-controlled trial in a cohort of stabilized schizophrenia patients to examine the efficacy of add-on hf-tRNS (100-640 Hz; 2 mA; 20 min) using a high definition 4 × 1 electrode montage (anode AF3, cathodes AF4, F2, F6, and FC4) in treating negative symptoms (ClinicalTrials.gov ID NCT04038788). Participants received either active hf-tRNS or sham twice daily for 5 consecutive weekdays. Primary outcome measure was the change over time in the Positive and Negative Syndrome Scale Factor Score for Negative Symptoms (PANSS-FSNS), which was measured at baseline, after 10-session stimulation, and at one-week and one-month follow-ups. Among 36 randomized patients, 35 (97.2%) completed the trial. Intention-to-treat analysis showed a significantly greater decrease in PANSS-FSNS score after active (-17.11%) than after sham stimulation (-1.68%), with a large effect size (Cohen's d = 2.16, p less then 0.001). The beneficial effect lasted for up to one month. In secondary-outcome analyses, the authors observed improvements with hf-tRNS of disorganization symptoms, unawareness of negative symptoms, subjective response to taking antipsychotics, and antipsychotic-induced extrapyramidal symptoms. No effects were observed on the neurocognitive performance and other outcome measures. Overall, hf-tRNS was safe and efficacious in improving negative symptoms. Our promising findings should be confirmed in a larger sample of patients with predominant negative symptoms.We investigated the association between discontinuation due to withdrawal of consent (DWC) in schizophrenia trials and the use of long-acting injectable antipsychotics (LAI-APs). In two categorical meta-analyses of randomized controlled trials, we compared DWC individual and pooled LAI-APs vs. (1) placebo and (2) oral antipsychotics (OAPs). We also performed conducted a single-group meta-analysis to calculate the average DWC and a meta-regression analysis to examine the association between the results of the meta-analyses and factors related to study design, treatment, and patients. We identified 52 studies (total adult patients = 18,675, LAI-APs = 12,613, placebo = 2,083, and OAPs = 3,979; median study duration = 32 weeks). DWC was higher for LAI-aripiprazole than for the placebo [risk ratio (95% confidence interval) = 1.70 (1.23-2.39)]. Neither pooled nor individual LAI-APs differed from the placebo for fluphenazine, olanzapine, paliperidone, and risperidone or from the OAPs for aripiprazole, fluphenazine, haloperidol, olanzapine, paliperidone, risperidone, and zuclopenthixol. The average DWC of each LAI-AP was as follows LAI-aripiprazole = 10.98%, LAI-fluphenazine = 7.65%, LAI-flupenthixol = 3.33%, LAI-haloperidol = 6.71%, LAI-olanzapine = 10.50%, LAI-paliperidone = 10.38%, LAI-perphenazine = 7.06%, LAI-risperidone = 10.39%, LAI-zuclopenthixol = 4.45%, pooled LAI-APs = 9.88%, and placebo = 11.17%. Meta-regression analysis demonstrated that publication year (β = 0.02), percentage of males (β = 0.02), and mean age (β = 0.05) were associated with an average DWC for pooled LAI-APs. Study duration (β = -0.03), percentage of males (β = 0.08), and patient status (β = -0.85) were associated with an average DWC for LAI-aripiprazole. Presence of a placebo arm (β = 1.60) was associated with an average DWC for LAI-fluphenazine. LAI-AP use was unlikely to be associated with DWC. link2 Although the LAI-aripiprazole had a higher DWC than did the placebo, its average DWC was similar to other those of LAI-APs.Aptamers are single-stranded nucleic acid sequences that can bind to target molecules with high selectivity and affinity. Most aptamers are screened in vitro by a combinatorial biology technique called systematic evolution of ligands by exponential enrichment (SELEX). Since aptamers were discovered in the 1990s, they have attracted considerable attention and have been widely used in many fields owing to their unique advantages. link3 In this review, we present an overview of the advancements made in aptamers used for biosensors and targeted therapy. For the former, we will discuss multiple aptamer-based biosensors with different principles detected by various signaling methods. For the latter, we will focus on aptamer-based targeted therapy using aptamers as both biotechnological tools for targeted drug delivery and as targeted therapeutic agents. Finally, challenges and new perspectives associated with these two regions were further discussed. We hope that this review will help researchers interested in aptamer-related biosensing and targeted therapy research.Lagopsis supina (Steph.) IK. -Gal. ex Knorr. has been used for centuries as an empiric treatment for blood stasis syndrome in China without scientific validation. The aim of this study was to evaluate for the first time the chemical profiling, efficacy and mechanism of L. supina ethanol extract (LS) and its four fractions (LSA∼D) in Dextran 500-induced acute blood stasis model rats. Oral administration of LS (229.0∼916.0 mg/kg) and LSC (17.6∼70.4 mg/kg) once daily for seven consecutive days significantly improved microcirculation hemodynamics function (blood flow, blood concentration and blood flow velocity), hemorheological parameters (whole blood viscosity, whole blood reduced viscosity, plasma viscosity, platelet aggregation rate, hematokrit, erythrocyte assembling index and erythrocyte deformation index), and coagulation parameters (thrombin time, prothrombin time, activated partial thromboplastin time, fibrinogen and antithrombin III). Furthermore, their markedly down-regulated thromboxane B2 and 6-keto-prostaglandin F1α levels. In addition, it significantly decreased tissue-type plasminogen activator (t-PA), urokinasetype plasminogen activator (u-PA) and plasminogen activator inhibitor-1 (PAI-1) levels, as well as PAI-1/t-PA and PAI-1/u-PA rations. In parallel, 51 chemical constituents were identified from LS based on ultra-high-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UHPLC-qTOF-MS/MS), and quantitative analysis showed that the two major constituents of stachysoside A and acteoside were present in 0.90 ± 0.01 and 1.36 ± 0.01 mg/g of the L. supina whole plant, respectively. These findings suggest that LS and LSC possess prominent anti-blood stasis effect on rats by modulating the anti-coagulation, anti-platelet activation and anti-fibrinolysis, and supports the traditional folk use of this plant.
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