Alzheimer's Disease (AD) is the most common neurodegenerative disease, which lacks disease-modifying therapeutics so far. Studies have shown that the dysfunction of the dopaminergic system is related ...to a variety of pathophysiology of AD, and the expression of Dopamine D2 receptor (DRD2) in the brains of AD patients and animal models is significantly downregulated, suggesting that DRD2 may represent a therapeutic target for AD. However, the strategy of targeting DRD2 for AD treatment still lacks some key experimental evidences. Here we show that DRD2 agonist Bromocriptine improved Aβ1-42 induced neuroinflammation, neuronal apoptosis, and memory deficits in mice.
For animal study, the mice have injected intracerebroventricularly (i.c.v.) with Aβ1-42(410 pmol/5 μl) to induced AD cognitive deficit model (Mazzola et al., 2003; van der Stelt et al., 2006). After 7 days, Bromocriptine (2.5 mg/kg, 5 mg/kg and 10 mg/kg) or normal saline was administered intragastrically once a day for 30 days. Behavioral tests about the Y maze and Morris water maze in mice were initiated on the twenty-fourth day of drug administration for 7 days.
In vivo and in vitro mechanism research revealed that Bromocriptine, via activating DRD2, promoted the recruitment of PP2A and JNK by scaffold protein β-arrestin 2, that repressed JNK-mediated transcription of proinflammatory cytokines and activation of NLRP3 inflammasome in microglia. Collectively, our findings suggest that Bromocriptine can ameliorate Aβ1-42 induced neuroinflammation and memory deficits in mice through DRD2/β-arrestin 2/PP2A/JNK signaling axis, which provides an experimental basis for the development of Bromocriptine as a drug for AD.
Thyroid nodules (TNs) are highly prevalent worldwide and have a pattern of female predominance. Bisphenol A (BPA) is an endocrine disruptor that can lead to adverse effects in human health. However, ...epidemiologic studies revealing the association between BPA exposure and TNs are limited and the results are inconsistent. We aimed to examine the association between urinary BPA and TNs in women who are more susceptible to TNs.
We conducted a case-control study with 1416 women aged 18 years or older (705 cases, 711 controls). All participants underwent thyroid ultrasonography. Urinary total BPA (free and conjugated) concentration was quantified using the HPLC-MS/MS. We analyzed the association between urinary BPA concentration and the risk of TNs using crude and multivariable logistic regression models. Participants were further stratified into thyroid autoantibody positive group (at least one positive) and thyroid autoantibody negative group (both negative) according to the thyroglobulin antibody (TGAb) and thyroid peroxidase antibody (TPOAb) levels, and restricted cubic spline regression was also applied to determine the possible nonlinear relationship between urinary BPA and TNs.
Compared with women in the first quartile, the odds of TNs was 72% (adjusted OR = 1.72, 95% CI: 1.25 to 2.35) higher for those in the second quartile, 54% (adjusted OR = 1.54, 95% CI: 1.12 to 2.12) higher for those in the third quartile, and 108% (adjusted OR = 2.08, 95% CI: 1.50 to 2.90) higher for those in the fourth quartile after adjusting for age, BMI, education, HDL-C, LDL-C, triglyceride, total cholesterol, urinary iodine, TGAb and TPOAb. When the study population was stratified into thyroid autoantibody positive group and thyroid autoantibody negative group, we found that only in the positive group, the association was significant in model 1 (crude OR = 2.80; 95% CI = 1.90 to 4.12), model 2 (adjusted OR = 2.84; 95% CI = 1.91 to 4.22), model 3 (adjusted OR = 4.01; 95% CI = 2.57 to 6.27) and model 4 (adjusted OR = 3.71; 95% CI = 2.36 to 5.83). Multivariable-adjusted restricted cubic spline analysis demonstrated a similar result that in the thyroid autoantibody positive group, the association between urinary BPA and TNs risk was near linear (P-overall <0.001; P-non-linear = 0.054).
In Chinese women, higher urinary BPA concentration was associated with increased risk of TNs only in those with positive thyroid autoantibodies. Moreover, this association was near linear, indicating that any rise in BPA exposure was associated with elevated TNs risk.
•We examined the association between BPA exposure and TNs risk in women.•BPA exposure was associated with increased TNs risk.•This association was observed only in women with positive thyroid autoantibodies.•Any rise in BPA exposure might be associated with elevated TNs risk.
Background. We conducted a systematic review and meta-analysis of existing literature to evaluate the different outcomes of microRNAs (miRNAs) in diabetic nephropathy (DN), including urinary albumin ...excretion rates, urinary albumin creatinine rates, glomerular filtration rate, HbAc1, and creatinine. Methods. Electronic databases including PUBMED, MEDLINE, and EMBASE were searched for eligible publications to July 2018. The following comparisons between treatment groups were included: normal group versus DN group; control group versus micro/macroalbuminuria group. Results. Twelve eligible studies that included 2500 participants were finally recruited in this meta-analysis. Fifteen miRNAs (miRNA-21, miRNA-181b, miRNA-194, miRNA-30, miRNA-215, and others) were upregulated whereas seven miRNAs (miRNA-26a, miRNA-126, miRNA-424, miRNA-574-3p, miR-223, miR-155, and miR-192) were downregulated in the DN group compared with control groups. The miR-133b, miR-342, miR-30, miR-192, miR-194, and miR-215 were significantly correlated in urinary albumin excretion rates (r=0.33, 95% CI= 0.26-0.39). miR-192, miR-217, miR-15b, miR-34a, and miR-636 were correlated with urinary albumin creatinine rates (r=0.69; 95% CI=0.12-0.92), while miR-133b, miR-345, miR-33, miR-326, miR-574-3p, miR-126, miR-217, miR-15b, miR-34a, and miR-636 were significantly correlated with HbAc1 (r =0.23, 95% CI = 0.15-0.31). There were twelve miRNAs that were closely related to the glomerular filtration rate (r=0.28, 95% CI =0.21-0.34). Creatinine (r=0.33, 95% CI = 0.22-0.40) was significantly different between normal and DN groups. Conclusions. The meta-analysis acquired the correlations between miRNAs and outcomes including UAER, UACR, eGFR, HbAc1, and creatinine in DN. It suggested that miRNAs may participate in the pathogenesis of DN process.
Background and Purpose
Dopamine protects the duodenal mucosa. Here we have investigated the source of dopamine in gastric juice and the mechanism underlying the effects of luminal dopamine on ...duodenal bicarbonate secretion (DBS) in rodents.
Experimental Approach
Immunofluorescence, UPLC‐MS/MS, gastric incubation and perfusion were used to detect gastric‐derived dopamine. Immunofluorescence and RT‐PCR were used to examine the expression of dopamine receptors in the duodenal mucosa. Real‐time pH titration and pHi measurement were performed to investigate DBS.
Key Results
H+‐K+‐ATPase was co‐localized with tyrosine hydroxylase and dopamine transporters in gastric parietal cells. Dopamine was increased in in vivo gastric perfusate after intravenous infusion of histamine and in gastric mucosa incubated, in vitro, with bethanechol chloride or tyrosine. D2 receptors were the most abundant dopamine receptors in rat duodenum, mainly distributed on the apical membrane of epithelial cells. Luminal dopamine increased DBS in a concentration‐dependent manner, an effect mimicked by a D2 receptor agonist quinpirole and inhibited by the D2 receptor antagonist L741,626, in vivo D2 receptor siRNA and in D2 receptor −/− mice. Dopamine and quinpirole raised the duodenal enterocyte pHi. Quinpirole‐evoked DBS and PI3K/Akt activity were inhibited by calcium chelator BAPTA‐AM or in D2 receptor−/− mice.
Conclusion and Implications
Dopamine in the gastric juice is derived from parietal cells and is secreted along with gastric acid. On arrival in the duodenal lumen, dopamine increased DBS via an apical D2 receptor‐ and calcium‐dependent pathway. Our data provide novel insights into the protective effects of dopamine on the duodenal mucosa.
Demulsifiers are considered the key materials for oil/water separation. Various works in recent years have shown that demulsifiers with polyoxypropylen epolyoxyethylene branched structures possess ...better demulsification effects. In this work, inspired by the chemical structure of demulsifiers, a novel superhydrophilic/underwater superoleophobic membrane modified with a polyoxypropylene polyoxyethylene block polymer was fabricated for enhanced separation of O/W emulsion. First, a typical polyoxypropylene polyoxyethylene triblock polymer (Pluronic F127) was grafted onto the poly styrene-maleic anhydride (SMA). Then, the Pluronic F127-grafted SMA (abbreviated as F127@SMA) was blended with polyvinylidene fluoride (PVDF) for the preparation of the F127@SMA/PVDF ultrafiltration membrane. The obtained F127@SMA/PVDF ultrafiltration membrane displayed superhydrophilic/underwater superoleophobic properties, with a water contact angle of 0° and an underwater oil contact angle (UOCA) higher than 150° for various oils. Moreover, it had excellent separation efficiency for SDS-stabilized emulsions, even when the oil being emulsified was crude oil. The oil removal efficiency was greater than 99.1%, and the flux was up to 272.4 L·m
·h
. Most importantly, the proposed F127@SMA/PVDF membrane also exhibited outstanding reusability and long-term stability. Its UOCA remained higher than 150° in harsh acidic, alkaline, and high-salt circumstances. Overall, the present work proposed an environmentally friendly and convenient approach for the development of practical oil/water separation membranes.
Seed germination and seedling development in nearly all orchid species rely on a symbiotic relationship with mycorrhizal fungi; however, this is not the case with all mycorrhizal fungi. This study ...aims to provide an understanding about the important role of mycorrhiza in seed germination and growth of Paphiopedilum barbigerum. Therefore, we isolated and identified endophytic fungi from the roots of wild P. barbigerum. The beneficial mycorrhizal fungi Epulorhiza sp. FQXY019 and Tulasnella calospora FQXY017 were screened by seed symbiotic germination tests and found to promote seed germination. However, only the seeds inoculated with FQXY019 progressed from the seed germination to rooting stage. This shows that mycorrhizal fungi and P. barbigerum have a specific relation at different growth phases. In addition, we selected FQXY019 and inoculated it into MS medium, B5 medium, OMA medium, and PDA medium. The results showed that FQXY019 co-cultured on PDA significantly promoted the increase in seedling fresh weight, leaf length, and root length (p < .01). Furthermore, it significantly promoted the root number and leaf number of seedlings compared with those co-cultured on MS, B5, and OMA media and control (p < .05). Thus, this study demonstrated the promoting effect of Epulorhiza sp. FQXY019 on seed germination and seedling development, making it an alternative method for the artificial propagation of P. barbigerum.
The automorphisms of bi-Cayley graphs Zhou, Jin-Xin; Feng, Yan-Quan
Journal of combinatorial theory. Series B,
January 2016, 2016-01-00, Letnik:
116
Journal Article
Recenzirano
Odprti dostop
A bi-Cayley graph Γ is a graph which admits a semiregular group H of automorphisms with two orbits. In this paper, the normalizer of H in the full automorphism group of Γ is determined. Applying ...this, a characterization of cubic edge-transitive graphs of order a 2-power is given. As byproducts, we answer a problem proposed in Godsil (1983) 16 regarding the existence of arc-regular non-normal Cayley graphs of order a 2-power, and construct the first known family of cubic semisymmetric graphs of order a 2-power.
Codonopsis pilosula is a kind of traditional Chinese medicine used to treat weak spleens, stomach problems, anemia, and fatigue. Polysaccharide is one of main components of Codonopsis pilosula. In ...this study, response surface methodology (RSM) was used to optimize the extraction parameters of Codonopsis pilosula polysaccharides (CPP) by fermentation. The exaction temperature (°C), yeast liquid volume (2 mg/ml, ml), and time (h) were employed effects. Results indicated that the best extraction conditions were the following: extraction temperature 24.75°C, yeast liquid volume 2.96 ml (5.92 mg), and a fermentation time of 21.03 hr. After purification with DE52 and Sephadex G‐100, the molecular structure was determined by ultraviolet–visible (UV) spectroscopy, Fourier transform infrared (FTIR) spectroscopy, and nuclear magnetic resonance (NMR) (1H and 13C). The monosaccharide composition of CPP1 was determined to be mannose (1.76%), glucose (97.38%), and arabinose (0.76%). CPP1 exhibited high antioxidant activities in scavenging ABTS radicals, ferreous ions, and superoxide ion radicals. Thus, CPP1 could be used as an antioxidant or functional food.
Response surface methodology (RSM) was used to optimize the extraction parameters of Codonopsis pilosula polysaccharides (CPPs) by fermentation.
This study presents a reactive transport model for the in-situ recovery of weathered crust elution-deposited rare earth ores and aims to provide predictive and optimization techniques for rare earth ...recovery. The model integrates Kerr's selection coefficient, dynamic reversible shrinking core model, and transport model to capture the dynamics of leaching fraction, rare earth elements (REEs), and exchangeable ions during in-situ leaching. The proposed model was validated through bench-scale equilibrium, kinetic, and column experiments, as well as numerical simulation. The results indicate that the deviation from using a single selection coefficient (referred to as 4.26 L2 mol−2 in this study) for modeling is acceptable. Both Darcy velocity and concentration of leaching solution mainly affect the peak value and bending degree of the post-peak leaching curve. Optimal cessation of leaching solution injection, such as substituting water after the peak of the leaching curve, enables effective conservation of leaching solution and reduction of environmental pollution. Differences of at least two orders of magnitude were observed between dynamic parameters derived from kinetic experiments (1.46 and 4.34 L mol−1 min−1) and those obtained from column experiments (2.60 × 10−3 and 1.71 × 10−2 L mol−1 min−1). This finding carries substantial implications for in-situ recovery and mineralization processes, highlighting the need for further investigation at the pore scale.
•A reactive transport model for in situ recovery of rare earth elements was derived.•The reactive transport model was verified by numerical simulation.•The notable disparity of kinetic coefficients in reactive flow process has been observed.•The influence of Darcy velocity and concentration of leaching solution is revealed.•A typical strategy is to choose the time to stop injection of leaching solution.
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