Acetylcholinesterase is regulated by exposure of ultraviolet B in skin keratinocytes: A potential inducer of cholinergic urticaria.

Cholinergic urticaria is a dermatological disease characterized by the presence of large patches of red skin and transient hives triggered by factors, such as exercise, sweating, and psychological tension. This skin problem is hypothesized to be attributed to a reduced expression of acetylcholinesterase (AChE), an enzyme responsible for hydrolyzing acetylcholine (ACh). Consequently, ACh is thought to the leak from sympathetic nerves to skin epidermis. The redundant ACh stimulates the mast cells to release histamine, triggering immune responses in skin. Here, the exposure of ultraviolet B in skin suppressed the expression of AChE in keratinocytes, both in in vivo and in vitro models. The decrease of the enzyme was resulted from a declined transcription of ACHE gene mediated by micro-RNAs, that is, miR-132 and miR-212. The levels of miR-132 and miR-212 were markedly induced by exposure to ultraviolet B, which subsequently suppressed the transcriptional rate of ACHE. In the presence of low level of AChE, the overflow ACh caused the pro-inflammatory responses in skin epidermis, including increased secretion of cytokines and COX-2. These findings suggest that ultraviolet B exposure is one of the factors contributing to cholinergic urticaria in skin.

Prenatal diesel exhaust exposure alters hippocampal synaptic plasticity in offspring.

Diesel exhaust particles (DEPs) are major air pollutants emitted from automobile engines. Prenatal exposure to DEPs has been linked to neurodevelopmental and neurodegenerative diseases associated with aging. However, the specific mechanism by DEPs impair the hippocampal synaptic plasticity in the offspring remains unclear. Pregnant C57BL/6 mice were administered DEPs solution via the tail vein every other day for a total of 10 injections, then the male offsprings were studied to assess learning and memory by the Morris water maze. Additionally, protein expression in the hippocampus, including CPEB3, NMDAR (NR1, NR2A, NR2B), PKA, SYP, PSD95, and p-CREB was analyzed using Western blotting and immunohistochemistry. The alterations in the histomorphology of the hippocampus were observed in male offspring on postnatal day 7 following prenatal exposure to DEPs. Furthermore, 8-week-old male offspring exposed to DEPs during prenatal development exhibited impairments in the Morris water maze test, indicating deficits in learning and memory. Mechanistically, the findings from our study indicate that exposure to DEPs during pregnancy may alter the expression of CPEB3, SYP, PSD95, NMDAR (NR1, NR2A, and NR2B), PKA, and p-CREB in the hippocampus of both immature and mature male offspring. The results offer evidence for the role of the NMDAR/PKA/CREB and CPEB3 signaling pathway in mediating the learning and memory toxicity of DEPs in male offspring mice. The alterations in signaling pathways may contribute to the observed damage to synaptic structure and transmission function plasticity caused by DEPs. The findings hold potential for informing future safety assessments of DEPs.

Yttrium and Niobium Elements Co-Doping and the Formation of Double Perovskite Structure Ba2YNbO6 in BCZT.

The (Ba0.85Ca0.15) (Ti0.90Zr0.10)O3 + x Y3+ + x Nb5+ (abbreviated as BCZT-x(Nb + Y), x = 0 mol%, 0.05 mol%, 0.1 mol%, 0.2 mol%, 0.3 mol%) lead-free piezoceramics samples were prepared by a traditional solid-state sintering method. And the effects of Yttrium and Niobium elements (Y3+ and Nb5+) co-doping on the defect, phase and structure, microstructure, and comprehensive electrical properties have been investigated. Research results show that the Y and Nb elements co-doping can dramatically enhance piezoelectric properties. It is worth noting that XPS defect chemistry analysis, XRD phase analysis and TEM results together show that a new phase of double perovskite structure Barium Yttrium Niobium Oxide (Ba2YNbO6) is formed in the ceramic, and the XRD Rietveld refinement and TEM results show the coexistence of the R-O-T phase. Both these two reasons together lead to significant performance improvements of piezoelectric constant (d33) and planar electro-mechanical coupling coefficient (kp). The functional relation between temperature and dielectric constant testing results present that the Curie temperature increases slightly, which shows the same law as the change of piezoelectric properties. The ceramic sample reaches an optimal performance at x = 0.1% of BCZT-x(Nb + Y), where d33 = 667 pC/N, kp = 0.58, εr = 5656, tanδ = 0.022, Pr = 12.8 µC/cm2, EC = 2.17 kV/cm, TC =92 °C, respectively. Therefore, they can be used as potential alternative materials to lead based piezoelectric ceramics.

Gut Microbiota from Short-Chain Chlorinated Paraffin-Exposed Mice Promotes Astrocyte Activation by Disrupting the Intestinal Tight Junction via Zonulin Upregulation.

Short-chain chlorinated paraffins (SCCPs) are novel toxicants in food and are reported to possess neurotoxicity. Here, we investigated the mechanism of SCCP-induced astrocyte activation and neuroinflammation. SCCP gavage induced astrocyte activation and neuronal cell death with the changes of gut microbiome and metabolites. Antibiotic cocktail administration to deplete the gut microbiome ameliorated the astrocyte activation and inflammation induced by SCCPs. In fecal microbiota transplantation (FMT) assays, mice that received transplanted gut microbiome from SCCP-treated mice showed increased astrocyte activation and elevated inflammatory response. In addition, SCCP exposure promotes zonulin expression and tight junction injury, and antibiotic cocktail administration inhibited that in the intestinal tract. Increased zonulin and tight junction injury were also observed in SCCPs_FMT mice. The zonulin inhibition protected the tight junction in the intestinal tract from SCCP exposure and suppressed astrocyte activation. In summary, this study proposes a novel possibility for SCCP-induced astrocyte activation and neurotoxicity by the gut microbiome-mediated zonulin expression and tight junction.

The ethanolic extract of peanut shell attenuates the depressive-like behaviors of mice through modulation of inflammation and gut microbiota.

Peanut shell is an agricultural byproduct being wasted on a large scale, which is in urgent need to be recycled. To fully utilize its pharmacological ingredients, e.g. luteolin, eriodyctiol, and 5,7-dihydroxychromone, we evaluated the curative effect of ethanol extract deriving from peanut shell (PSE) in treating chronic unpredictable mild stress (CUMS)-induced depressive mice. The chronic stress lasted for 10 weeks, and PSE at 100-900 mg/kg/day was gavaged to mice in the last 2 weeks of modeling. The depressive behaviors were assessed by analyses of sucrose preference, tail suspension, and forced swimming. The brain injury was demonstrated by Hematoxylin and Eosin (H&E), Nissl body, and TdT-mediated dUTP nick end labeling (TUNEL) stainings in the mouse hippocampus. Biochemical indicators were analyzed, including levels of neurotrophic factors, neurotransmitters, stress hormones, and inflammatory mediators. The feces were collected for the 16S rDNA sequencing of gut microbiome. Administration of PSE improved the sucrose water consumption of depressive mice, while it decreased the immobile time in tail suspension and forced swimming tests. Meanwhile, the anti-depressive effect of PSE was supported by ameliorated histochemical staining, increased levels of neurotrophic factors and neurotransmitters, as well as down-regulated stress hormones. Furthermore, the treatment of PSE was able to mitigate the levels of inflammatory cytokines in brain, serum, and small intestine. Besides, the tight junction proteins, e.g., occludin and ZO-1, of gut showed elevated expressions, which coincided with the elevated abundance and diversity of gut microbiota upon PSE treatment. This study validated the therapeutic efficacy of PSE in fighting against depression, as well as its modulatory action on inflammation and gut microbiota, which promoted the recycling of this agricultural waste to be health supplements of added value.

Effects of polystyrene nanoplastic gestational exposure on mice.

Airborne plastic particles have received increasing attention due to their ubiquity in the atmosphere and potential human health risks. Previous studies have demonstrated that early-life exposure to environmental toxicants is associated with abnormal metabolic function. However, the impact of exposure to polystyrene nanoplastics (PSNPs) through inhalation on the development of non-alcoholic fatty liver disease (NAFLD) in mothers and offspring remains unknown. In the present study, mice were gestationally exposed to PSNPs at different doses (0, 1, 5, and 25 µg µl-1) through inhalation to investigate health hazards to the dam at weaning and to adult offspring. Gestational exposure to PSNPs at high doses significantly induced hepatic steatosis in the dam and upregulated genes involved in de novo lipogenesis, fatty acids (FAs) uptake, and triacylglycerol (TG) synthesis in the monoacylglycerol acyltransferase pathway. Gestational exposure to high doses of PSNPs led to hepatic steatosis in adult female offspring but not male offspring, and expression levels of genes related to FAs uptake and TG synthesis in the glycerol 3-phosphate pathway were significantly elevated. Collectively, our data demonstrate that gestational exposure to airborne PSNPs induced different development processes of NAFLD in the dam and offspring, providing vital data about plastic particulate toxicology.

Trace elements in hair or fingernail and gastroesophageal cancers: results from a population-based case-control study.

BACKGROUND: Growing evidence suggests that environmental factors probably play important roles in the development of gastroesophageal cancers (GOC), however, the effects of trace elements on GOC remain unclear. OBJECTIVE: To assess the effect of trace elements on GOC and the effect modification by other factors. METHODS: Hair and fingernail samples were collected from GOC cases and controls in a population-based case-control study in Taixing, China, and were used to detect the concentrations of 12 trace elements using inductively coupled plasma mass spectrometry. Unconditional logistic regression models were used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) for concentrations of 12 trace elements in association with GOC after adjusting the other factors. RESULTS: A total of 830 hair samples (581 controls and 249 cases) and 895 fingernail samples (559 controls and 336 cases) were included. Compared to the lowest-tertile concentration, the higher tertiles of Ca, Zn, Fe, Al, Cr, Pb, Se, and V were positively associated with GOC, while the higher tertiles of Mg, Mn, Sr, and As were inversely associated with GOC. Significant interactions between the hair level of Cr and two other risk factors, including smoking (P for interaction = 0.044) and alcohol drinking (P for interaction = 0.028), were observed in association with GOC. SIGNIFICANCE: The current study reveals that these 12 trace elements in hair and fingernails are associated with GOC to varying degrees. Further studies and animal experiments are needed to clarify the associations and explore potential mechanisms. IMPACT STATEMENT: The role of trace elements in the development or inhibition of gastroesophageal cancers (GOC) remains unclear. In this study, we further explored the associations between 12 trace elements and GOC based on a population-based case-control study conducted in Taixing, China. Higher levels of Ca, Zn, Fe, Al, Cr, Pb, Se, and V were positively associated with increased GOC, while inverse associations between higher levels of Mg, Mn, Sr, As, and GOC were observed. Observed associations were consistent in hair and fingernail samples. Moreover, interaction effects between hair level of Cr and smoking or alcohol drinking were identified.

Ferroptosis Is Involved in Sex-Specific Small Intestinal Toxicity in the Offspring of Adult Mice Exposed to Polystyrene Nanoplastics during Pregnancy.

Nanoplastics are common contaminants in the living environment. Thus far, no investigations have focused on small intestinal injury in the offspring of adult mice that were exposed to nanoplastics through the respiratory system during pregnancy. Here, we evaluated potential intestinal injury in the offspring of adult mice that were subjected to maternal 80 nm polystyrene nanoparticle (PS-NP) exposure during gestation. PS-NP exposure significantly reduced the birth weight of female mice compared with male mice. However, the adult body weights of the female and male offspring were substantially greater in the PS-NP-exposed groups. Additionally, we found that exposure to PS-NPs during pregnancy caused histological changes in the small intestines of both female and male offspring. Mechanistic analysis revealed upregulation of reactive oxygen species in the small intestines, as indicated by changes in the levels of superoxide dismutase (SOD) and malondialdehyde (MDA). Furthermore, exposure to PS-NPs led to downregulation of GPx4, FTH1, and FTL protein levels, indicating initiation of ferroptosis. Notably, the changes in mRNA expression levels of GPx4, FTH1, and FTL differed between female and male offspring. Although all phenotypes failed to demonstrate classic dose-dependent effects, the data imply that small intestinal toxicity is greater in female offspring than in male offspring. Our results suggest that PS-NP exposure during pregnancy causes sex-specific small intestinal toxicity, which might contribute to reactive oxygen species activation and subsequent ferroptosis. Overall, this study showed toxic effects in offspring after PS-NP exposure during pregnancy.

The UV-induced uptake of melanosome by skin keratinocyte is triggered by α7 nicotinic acetylcholine receptor-mediated phagocytosis.

The melanosome is an organelle that produces melanin for skin pigmentation, which is synthesized by epidermal melanocytes, subsequently transported and internalized by epidermal keratinocytes. Exposure to ultraviolet (UV) from sunlight radiation is a major stimulator of melanosome uptake by keratinocytes. Acetylcholine (ACh) is known to be released by keratinocytes under UV exposure, which regulates melanin production in melanocytes by participating in which has been named as 'skin synapse'. Here, the role of cholinergic molecules, i.e. ACh and α7 nicotinic acetylcholine receptor (nAChR), in regulating melanosome uptake through phagocytosis by keratinocytes was illustrated. In cultured keratinocytes (HaCaT cells), the fluorescent beads at different sizes imitating melanosomes, or melanosomes, were phagocytosed under UV exposure. The UV-induced phagocytosis in keratinocytes was markedly increased by applied ACh, an acetylcholinesterase (AChE) inhibitor or an α7 nAChR agonist. By contrast, the antagonist of α7 nAChR was able to fully block the UV-induced phagocytosis, suggesting the role of α7 nAChR in this event. The intracellular Ca++ mobilization was triggered by UV exposure, accounting for the initiation of phagocytosis. The blockage of UV-mediated Ca++ mobilization, triggered by BAPTA-AM or α7 nAChR antagonist, resulted in a complete termination of phagocytosis. Besides, the phosphorylation of cofilin, as well as expression and activation of RhoA, accounting for phagocytosis was induced by UV exposure: the phosphorylation was blocked by BAPTA-AM or α7 nAChR antagonist. The result suggests that the cholinergic system, especially α7 nAChR, is playing a regulatory role in modulating melanosome uptake in keratinocytes being induced by UV exposure.

Exposure to short-chain chlorinated paraffins induces astrocyte activation via JAK2/STAT3 signaling pathway.

In the last few decades, short-chain chlorinated paraffins (SCCPs) have become the most heavily produced monomeric organohalogen compounds, and have been reported to induce multiple organ toxicity. However, the effects of SCCPs on the central nervous system are unknown. In the present study, we show that SCCP exposure induced astrocyte proliferation and increased the expression of two critical markers of astrocyte activation, glial fibrillary acidic protein and inducible nitric oxide synthase, in vivo and in vitro. SCCP exposure also increased inflammatory factory gene expression. Moreover, SCCP treatment triggered Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signalling, as shown by increased phosphorylation and STAT3 translocation to the nucleus. Both JAK2 and STAT3 inhibition effectively attenuated SCCP-induced astrocyte activation. Finally, JAK2 inhibition significantly rescued STAT3 phosphorylation and nuclear translocation. Taken together, JAK2/STAT3 pathway activation contributed to SCCP-induced astrocyte activation. These data will help elucidate the molecular mechanism underlying SCCP-induced neurotoxicity.

The water extract of Aloe vera prevents fluoxetine-induced multiple-drug resistance of E. coli by inhibiting reactive oxygen species formation and membrane permeability.

BACKGROUND: The medication of synthetic chemical is one of the main treatments for depressive disorders. Different lines of evidence reveal that a long-term exposure to anti-depressants, e.g., fluoxetine, is causing multiple-drug resistance (MDR) of gut microbiomes. The MDR bacterial strains in gut pose a threat to intestinal balance and treatment of future microbial infection. Effective strategies are thus in urgent need to prevent the anti-depressant-mediated MDR of gut microbes. PURPOSE: We aimed to investigate the potential role of Aloe vera (L.) Burm. f. (aloe; Liliaceae family) to prevent MDR of E. coli being co-cultured with fluoxetine. METHODS: The extract of A. vera was co-cultured with E. coli and fluoxetine to analyze the preventive effect of MDR. To figure out the mechanistic action, the formation of reactive oxygen species (ROS) and the expression of key biomarkers, including outer membrane proteins (OmpF and OmpC), superoxidative stress activator (SoxS) and efflux pumps (AcrA/B-TolC), were determined in E. coli being treated with fluoxetine and aloe extract. In addition, the genetic mutation of transcriptional factors of these biomarkers was determined in the fluoxetine-treated E. coli. RESULTS: The water extract of A. vera showed considerable potential to reduce the number of fluoxetine-mediated MDR colonies. The extract robustly suppressed the formation of ROS in E. coli. However, thiourea and N-acetylcysteine, two well-known antioxidants, showed no activity in preventing the formation of bacterial MDR. Additionally, A. vera extract directly affected the fluoxetine-triggered early stress response of E. coli and the expression of downstream genes. Meanwhile, A. vera extract was able to inhibit the genetic mutation of SoxR gene in E. coli, as induced by co-cultured with fluoxetine. By fractionation of the aloe extract, the ethanol precipitate, composing mainly polysaccharides, showed robust activity in preventing the fluoxetine-mediated MDR. CONCLUSION: This study therefore suggested that the extract of A. vera could be an adjuvant agent to combat bacterial MDR during anti-depressant treatment.

Relationships between urinary metals concentrations and cognitive performance among U.S. older people in NHANES 2011-2014.

Background: Epidemiological evidence on Urine metals and cognitive impairment in older individuals is sparse and limited. The goal of this study was to analyze if there was a link between urinary metal levels and cognitive performance in U.S. people aged 60 and up. Methods: The National Health and Nutrition Examination Survey (NHANES) data from 2011 to 2014 were utilized in this cross-sectional analysis. Memory function was quantified using the following methods: Established Consortium for Word Learning in Alzheimer's Disease (CERAD-WL) (immediate learning and recall and delayed recall), Animal Fluency Test (AFT), and Digit Symbol Substitution Test (DSST). An inductively coupled plasma mass spectrometry (ICP-MS) was used to estimate urine metal concentrations. The connection of Urine metals level with cognitive function was investigated employing binary logistic regression and restricted cubic spline models. Results: A total of 840 participants aged 60 years and over were enrolled in this study. After controlling for confounders, the association between cadmium, barium, cobalt, cesium, manganese, and thallium and poor cognitive performance showed significance in multiple logistic regression compared to the lowest quartile of metals. In the DSST test, the weighted multivariate adjusted ORs (95% CI) for cadmium in the highest quartile, barium and cesium in the third quartile were 2.444 (1.310-4.560), 0.412 (0.180-0.942) and 0.440 (0.198-0.979), respectively. There were L-shaped associations between urine cesium, barium, or manganese and low cognitive performance in DSST. Urine lead, molybdenum and uranium did not show any significant relationships with cognitive impairment, respectively, compared to the respective lowest quartile concentrations. Conclusion: The levels of barium (Ba), cobalt (Co), cesium (Cs), manganese (Mn), and thallium (Tl) in urine were found to be negatively related to the prevalence of impaired cognitive performance in our cross-sectional investigation. Higher cadmium (Cd) levels were associated with cognitive impairment.

Level-specific associations of urinary antimony with cognitive function in US older adults from the National Health and Nutrition Examination Survey 2011-2014.

BACKGROUND: We have looked at antimony (Sb) as a new neurotoxin which causes neuronal apoptosis in animal studies. At the population level, however, there is no direct evidence for a relationship between Sb exposure and cognitive performance. METHOD: The study comprehensively assessed the correlation between urinary antimony levels and cognitive test scores in 631 creatinine-corrected older persons using data from the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2014. RESULTS: Using logistic regression, the study looked at the prevalence of cognitive impairment at different levels of urine antimony concentrations and found that, after controlling for covariates, higher doses of urinary antimony were positively associated with cognitive function compared to controls, odds ratio (ORs) with 95% confidence interval (CI) were 0.409 (0.185-0.906) and 0.402 (0.186-0.871) respectively. Restricted cubic spline curves showed a non-linear and dose-specific correlation between urinary antimony and cognitive performance, with lower doses associated with better cognitive performance, while higher doses may be associated with cognitive impairment. CONCLUSIONS: Our data provide evidence for a correlation between Sb and cognitive function at the population level, although the specific mechanisms need to be investigated further.

The inclusion of extract from aerial part of Scutellaria baicalensis in feeding of pearl gentian grouper (Epinephelus fuscoguttatus♀ × Epinephelus lanceo-latus♂) promotes growth and immunity.

The root of Scutellaria baicalensis (Scutellaria Radix) has been used as herbal medicine for years in China; however, its stem and leaf (aerial part) are considered as waste. The water extract of aerial part of S. baicalensis, named as SBA, having anti-microbial property has been applied in fish aquaculture. To extend the usage of SBA in fish feeding, SBA was employed to feed pearl gentian grouper (a hybrid of Epinephelus fuscoguttatus♀ × Epinephelus lanceolatus♂), and subsequently the total fish output, the levels of digestive enzymes and inflammatory cytokines were determined. Feeding the fish with different doses of SBA for two months, the body length and weight were significantly increased by 5%-10%. In parallel, the expressions of alkaline phosphatase and growth-related factors in bone, liver and muscle of SBA-fed fish were doubled, which could account the growth promoting effect of SBA. Besides, the activity of digestive enzyme, lipase, and the expressions of anti-inflammatory cytokines were markedly stimulated by 2-3 times under the feeding of 3% SBA-containing diet. The results indicated the growth promoting activity of SBA in culture of pearl gentian grouper, as well as the effect of SBA in strengthening the immunity. These beneficial effects of SBA feeding can increase the total yield of pearl gentian grouper in aquaculture. Thus, the re-cycle of waste products during the farming of S. baicalensis herb in serving as fish feeding should be encouraged.

Capsaicin, a Phytochemical From Chili Pepper, Alleviates the Ultraviolet Irradiation-Induced Decline of Collagen in Dermal Fibroblast via Blocking the Generation of Reactive Oxygen Species.

Capsaicin, a major ingredient in chili pepper, has broad pharmaceutical applications, including relieving pain, anti-inflammation, and treating psoriasis. In dermatological biology, capsaicin has been shown to prevent the ultraviolet (UV)-induced melanogenesis via TRPV1 receptor. To strengthen the roles of capsaicin in skin function, the damaged skin, triggered by exposure to UV, was reversed by capsaicin in both in vitro and in vivo models. In cultured dermal fibroblasts, the exposure to UV induced a decrease of collagen synthesis and increases expression of matrix metalloproteinases (MMPs), generation of reactive oxygen species (ROS), and phosphorylation of Erk and c-Jun, and these events subsequently led to skin damage. However, the UV-mediated damages could be reversed by pre-treatment with capsaicin in a dose-dependent manner. The effect of capsaicin in blocking the UV-mediated collagen synthesis was mediated by reducing generation of ROS in dermal fibroblasts, instead of the receptor for capsaicin. Hence, capsaicin has high potential value in applying as an agent for anti-skin aging in dermatology.

GPX4 degradation via chaperone-mediated autophagy contributes to antimony-triggered neuronal ferroptosis.

Exposure to antimony (Sb), recently identified as a nerve pollutant, can result in neuron damage; but, associated-neurotoxicological mechanisms were still not clear. Herein, we assessed the role of ferroptosis in Sb-mediated neurotoxicity and clarified the underlying mechanism. Following Sb exposure, ferroptosis was significantly promoted in vivo and in vitro. Moreover, following use of ferrostatin-1 (fer-1) to inhibit ferroptosis, Sb-induced ferroptosis in PC12 cells was effectively attenuated. Sb accelerated lysosomal transport and subsequent degradation of glutathione peroxidase 4 (GPX4), resulting in ferroptosis. Furthermore, chaperone-mediated autophagy (CMA) was activated following treatment with Sb, while inhibition of CMA by lysosomal associated protein 2 A (LAMP2A) knockdown attenuated Sb-induced GPX4 degradation. Sb treatment also increased expression of the chaperones heat shock cognate protein 70 (HSC70) and heat shock protein 90 (HSP90) and the lysosome receptor LAMP2A, and increased binding of HSP90, HSC70, and LAMP2A with GPX4 was observed, indicating increased formation of the chaperone-GPX4 complex. Finally, GPX4 overexpression significantly protected PC12 cells from activation of Sb-stimulated ferroptosis and subsequent cytotoxicity. Collectively, our results provide a original mechanism by which Sb triggers neurotoxicity, to concluded that Sb stimulates neuronal ferroptosis through CMA-mediated GPX4 degradation.

Regulation of acetylcholinesterase during the lipopolysaccharide-induced inflammatory responses in microglial cells.

The non-classical function of acetylcholine (ACh) has been reported in neuroinflammation that represents the modulating factor in immune responses via activation of α7 nicotinic acetylcholine receptor (α7 nAChR), i.e., a cholinergic anti-inflammatory pathway (CAP). Acetylcholinesterase (AChE), an enzyme for ACh hydrolysis, has been proposed to have a non-classical function in immune cells. However, the involvement of AChE in neuroinflammation is unclear. Here, cultured BV2 cell, a microglial cell line, and primary microglia from rats were treated with lipopolysaccharide (LPS) to induce inflammation and to explore the regulation of AChE during this process. The expression profiles of AChE, α7 nAChR, and choline acetyltransferase (ChAT) were revealed in BV2 cells. The expression of AChE (G4 form) was induced significantly in LPS-treated BV2 cells: the induction was triggered by NF-κB and cAMP signaling. Moreover, ACh or α7 nAChR agonist suppressed the LPS-induced production of pro-inflammatory cytokines, as well as the phagocytosis of microglia, by activating α7 nAChR and followed by the regulation of NF-κB and CREB signaling. The ACh-induced suppression of inflammation was abolished in AChE overexpressed cells, but did not show a significant change in AChE mutant (enzymatic activity knockout) transfected cells. These results indicate that the neuroinflammation-regulated function of AChE may be mediated by controlling the ACh level in the brain system.

Screening and mechanisms of novel angiotensin-I-converting enzyme inhibitory peptides from rabbit meat proteins: A combined in silico and in vitro study.

Bioactive peptides derived from food proteins have various physiological roles and have attracted increasing attention in recent years. In this study, two novel ACE inhibitory peptides (EACF and CDF), screened from rabbit meat proteins using in silico methods, exhibited strong inhibitory effects in vitro. EACF and CDF were competitive and non-competitive inhibitors with half-maximal inhibitory concentrations of 41.06 ± 0.82 µM and 192.17 ± 2.46 µM, respectively. Molecular docking experiments revealed that EACF established eight H-bond interactions in the S1 and S2 pockets, and a metal-acceptor interaction with Zn 701. CDF shared four H-bond interactions in the S1 pocket of ACE. The results suggested that rabbit meat proteins could be a suitable material for the preparation of ACE inhibitory peptides, and that virtual screening is an effective, accurate and promising method for the discovery of novel active peptides.

Feeding containing the aerial part of Scutellaria baicalensis promotes the growth and nutritive value of rabbit fish Siganus fuscescens.

The root of Scutellaria baicalensis (Scutellaria Radix) has been used as herbal medicine for years, while its stem and leaf (aerial part) are considered as waste. The water extract from the aerial part of S. baicalensis (named as SBA) being included in the feeding of Siganus fuscescens (grey rabbit fish) has been shown to replace antibiotics in aquaculture with excellent outcome. To strengthen the usage of SBA in fish feeding, the total fish output and its nutritive value were determined here. Feeding the fishes with different doses of SBA for a month, the body length and weight were significantly increased after intake of standard feed containing 1% SBA. In parallel, the expressions of alkaline phosphatase and growth-related factors in bone, liver, and muscle of 1% SBA-fed fishes were markedly increased, suggesting the beneficial effects of SBA. The composition of amino acid and fatty acid in fish muscle, after intaking 1% SBA-containing feed, was altered. In SBA-fed fish muscle, the amounts of threonine and methionine were increased, while the amount of leucine was decreased, as compared with control group. The amounts of fatty acids, including docosahexaenoic acid, phosphatidylcholine, and phosphatidylethanolamine, were increased in the 1% SBA-fed fish, while the amounts of triglycerides were decreased. The results indicated the growth-promoting activity of SBA in an in vivo culture of S. fuscescens, as well as to increase the nutritive values of the muscle. Thus, the re-cycle of waste products during the farming of S. baicalensis herb in serving as fish feeding should be encouraged.

Antimony-induced astrocyte activation via mitogen-activated protein kinase activation-dependent CREB phosphorylation.

Recent studies suggest that the chemical element antimony (Sb) is neurotoxic; however, the molecular mechanisms behind Sb-related neuronal damage are currently unknown. In this study, we found that Sb exposure promoted astrocyte proliferation and increased the expression of inducible nitric oxide synthase (iNOS) and glial fibrillary acidic protein (GFAP), two key protein markers of reactive astrogliosis, at both the gene and protein level, suggesting that Sb induced astrocyte activation. Moreover, the p38 mitogen-activated protein kinase (p38 MAPK) and extracellular signal-related kinase (ERK) pathways were activated following Sb exposure. Inhibition of p38 MAPK reduced Sb-induced iNOS and GFAP upregulation, while inhibiting ERK reduced GFAP expression only, in Sb-exposed C6 cells. Sb treatment also induced the phosphorylation of cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB), and the inhibition of CREB caused a reduction in Sb-induced GFAP and iNOS expression. Furthermore, inhibiting both p38 MAPK and ERK effectively alleviated CREB phosphorylation in Sb-exposed C6 cells. Taken together, our results suggest that p38 MAPK and ERK activation mediate Sb-induced astrocyte activation through CREB phosphorylation. These results help to clarify the molecular mechanisms underlying Sb-associated neurotoxicity.