Mechanisms of electroacupuncture relieves uterine smooth muscle spasm in dysmenorrhea rats based on Rho/ROCK signaling pathway. / 基于Rho/ROCKä¿¡å·é€šè·¯æŽ¢è®¨ç”µé’ˆä»»è„‰ã€ç£è„‰ç»ç©´ç¼“è§£ç±»ç—›ç»æ¨¡åž‹å¤§é¼ å­å®«å¹³æ»‘è‚Œç—‰æŒ›çš„æœºåˆ¶.

OBJECTIVES: To investigate the effect of electroacupuncture (EA) on Rho/Rho-associated coiled-coil-forming kinases (ROCK) signaling pathway of uterus tissue in rats with dysmenorrhea, so as to explore the underlying mechanism of EA treating primary dysmenorrhea (PD) and uterine smooth muscle spasm, and to observe whether there is a difference in the effect of meridian acupoints in Conception Vessel (CV) and Governer Vessel (GV). METHODS: Sixty female SD rats were randomly divided into saline, model, CV, GV, and non-acupoint groups, with 12 rats in each group. The dysmenorrhea model was established by subcutaneous injection of estradiol diphenhydrate combined with intraperitoneal injection of oxytocin (OT). EA (2 Hz) was applied to "Qihai" (CV6) and "Zhongji" (CV3) for CV group, "Mingmen" (GV4) and "Yaoshu" (GV2) for GV group, "non-acupoint 1" and "non-acupoint 3" on the left side for non-acupoint group, and manual acupuncture was applied to "Guanyuan" (CV4) for CV group, "Yaoyangguan" (GV3) for GV group, "non-acupoint 2" on the left side for non-acupoint group. The treatment was conducted for 20 min each time, once daily for 10 days. The writhing score was evaluated. The smooth myoelectric signals of rats' uterus in vivo were recorded by multi-channel physiological recorder. The uterine histopathological changes were observed by HE staining. The contents of prostaglandin F2α (PGF2α), OT and calcium ion (Ca2+) in uterine tissue of rats were detected by ELISA. The protein and mRNA expression levels of smooth muscle 22-α (SM22-α), RhoA and ROCKⅡ in uterine tissue were detected by Western blot and fluorescence quantitative PCR, respectively. RESULTS: Compared with the saline group, the writhing score of rats in the model group was increased (P<0.01), the amplitude voltage of uterine smooth muscle in vivo was elevated (P<0.01), the contents of PGF2α, OT and Ca2+, the protein and mRNA expression of SM22-α, RhoA and ROCK Ⅱ in uterine tissue were all increased (P<0.01). Compared with the model and the non-acupoint groups, the writhing scores of the CV and the GV groups were decreased (P<0.01, P<0.05), the amplitude voltage of uterine smooth muscle was decreased (P<0.01), the contents of PGF2α, OT and Ca2+ in uterine tissue were decreased (P<0.01, P<0.05), and the protein expression and mRNA expression of SM22-α, RhoA and ROCKⅡ in uterine tissue were decreased (P<0.01, P<0.05). HE staining showed extensive exfoliation of uterine intima with severe edema and increased glandular secretion in the model group, which was alleviated in the CV and GV groups. CONCLUSIONS: EA at acupoints of CV and GV can significantly reduce the writhing score, uterine smooth muscle amplitude voltage, pathological injury degree of uterus, and relieve spasm of uterine smooth muscle in dysmenorrhea rats, which may be related to its effect in regulating PGF2α and OT contents, inhibiting the Rho/ROCK signaling pathway, and reducing the SM22-α, RhoA, ROCKⅡ protein and mRNA expression, and Ca2+ content in uterine tissue.

Sexual dimorphism in the gut microbiota and sexual dimorphism in chronic diseases: Association or causation?

Understanding the sexual dimorphism in diseases is essential to investigate the pathogenesis of some chronic diseases (e.g., autoimmune diseases, etc). The gut microbiota has been found to show a notable impact on the pathology of several chronic diseases in recent years. Intriguingly, the composition of the gut microbiota varies between sexes. Here, we reviewed 'facts and fiction' regarding sexual dimorphism in chronic diseases and sexual dimorphism in the gut microbiota respectively. The association and causative relationship between them aiming to elucidate the pathological mechanisms of sexual dimorphism in chronic diseases were further explored. The development of gender-special food products based on the sexual dimorphism in the gut microbiota were recommended, which would be beneficial to facilitating the personalized treatment.

Phytochelatin-Mediated Cultivar-Dependent Cd Accumulations of Lactuca sativa and Implication for Cd Pollution-Safe Cultivars Screening.

Cd pollution-safe cultivar (Cd-PSC) is a feasible strategy to minimize Cd contamination in leafy vegetables. The shoot Cd concentrations of 23 Lactuca sativa cultivars under Cd stress ranged from 0.124 to 2.155 mg·kg-1 with a maximum cultivar difference of 8 folds. Typical Cd-PSC C16 (L) and high-Cd-accumulating cultivar C13 (H) were screened to investigate the mechanisms of Cd accumulations in L. sativa through determining Cd concentrations, Cd subcellular distributions, phytochelatin profiles, and phytochelatin biosynthesis-related genes' expressions. Higher Cd distribution in a heat stable fraction in C13 (H) indicated that the high Cd accumulation trait of C13 (H) mainly depended on the Cd-phytochelatin complexes. Root phytochelatin concentrations were significantly elevated in C13 (H) (5.83 folds) than in C16 (L) (2.69 folds) (p < 0.05) under Cd stress. Significantly downregulated expressions of glutathione S-transferase rather than the regulation of phytochelatin synthesis genes in the root of C13 (H) might be responsible for sufficient glutathione supply for phytochelatins synthesis. These findings suggested that phytochelatin elevation in C13 (H) would favor the Cd root to shoot transportation, which provides new insights into the phytochelatin-related cultivar-dependent Cd accumulating characteristic in L. sativa.

Management of allergic rhinitis improves clinical outcomes of difficult-to-treat tic disorders or attention-deficit/hyperactivity disorders.

AIMS: This case series aimed to evaluate the effects of treatment for allergic rhinitis (AR) in AR-diagnosed children with previous diagnosis of tic disorders/attention-deficit/hyperactivity disorders (TD/ADHD) but unresponsive to behavioral or medical treatment. MATERIALS AND METHODS: Between July 2016 and June 2021, children diagnosed with AR in our hospital were enrolled. All were diagnosed with TD/ADHD refractory to behavioral or medical treatment. The demography and clinical information were collected from medical records. The outcomes were visual analogue scale (VAS) for AR severity, Yale Comprehensive Tic Severity Scale (YGTSS) for TD symptoms, and Attention-Deficit Hyperactivity Screening Scale (SNAP-IV) for ADHD symptoms. RESULTS: A total of 27 children (18 boys, 9 girls) were included, with a mean age 7.4 ± 2.9 years (3 - 17 years). They had undergone behavioral or medical treatment of TD/ADHD for 3.6 ± 1.9 years but without significant improvement in TD/ADHD symptoms. After 2-6 months of systematic treatment for AR, VAS was decreased to 0.4 ± 0.1 from 0.8 ± 0.2, YGTSS to 3.5 ± 0.7 from 6.8 ± 1.4, and SNAP-IV to 0.4 ± 0.1 from 0.6 ± 0.2 (all p < 0.001). No recurrence of TD/ADHD symptoms was reported during a mean follow-up of 2.4 ± 1.1 years (0.5 - 5 years). CONCLUSION: AR treatment improves TD/ADHD outcomes in children with difficult-to-treat TD/ADHD. In TD/ADHD children who are unresponsive to behavioral or drug treatment and have AR-related symptoms, AR examination and treatment are recommended for better prognosis.

Macathioureas A-D, four new thiourea analogues from the roots of Lepidium meyenii.

Macathioureas A-D (1-4), four new thiourea derivatives with a carbamothioylpyrrolidine-2-carboxamide framework, were isolated from the roots of Lepidium meyenii (Maca) collected from Qujing, Yunnan Province of China. Their structures were identified based on extensive spectroscopic data, including 1D NMR, 2D NMR, and HRESIMS techniques. Their absolute configurations were assigned as 7S by the comparison of the experimental and predicted electronic circular dichroism (ECD) spectra. All the thiourea analogues were tested for their cytotoxicities against five human cancer cell lines. However, no significant activities were detected at concentrations up to 40 µM.

The gut-brain axis: Effect of electroacupuncture pretreatment on learning, memory, and JNK signaling in D-galactose-induced AD-like rats.

Objectives: To examine the effect and potential mechanism of electroacupuncture (EA) pretreatment in spatial learning, memory, gut microbiota, and JNK signaling in D-galactose-induced AD-like rats. Materials and Methods: The AD-like rat model was generated by intraperitoneal injection of D-galactose. Morris water maze was used to determine spatial learning and memory ability, Real-time PCR to determine intestinal flora levels, ELISA to determine tryptophan (Trp) and 5-HT levels in the colon and hippocampal tissues, immunofluorescence to determine 5-HT levels in enterochromaffin cells (ECs), and immunoblotting to determine JNK signaling protein levels in hippocampal tissues. Results: Electroacupuncture pretreatment significantly reduced escape latency and prolonged exploration time in the target quadrant, and significantly increased the relative DNA abundance of Lactobacillus and Bifidobacterium. Meanwhile, electroacupuncture pretreatment also reduced colonic 5-HT levels and increased hippocampal 5-HT levels. Moreover, electroacupuncture pretreatment significantly inhibited hippocampal JNK pathway-related protein expression, including 5-HT6R, JNK, p-JUNK, c-JUN, and p-c-Jun. And the combination of GV20 and ST36 was more effective than single acupoints. Conclusion: Electroacupuncture pretreatment improved the learning and memory ability of D-galactose-induced AD-like model rats, changed the gut microbiota composition, and the mechanism may be related to the gut-brain axis and the JNK signaling pathway. In addition, the combination of GV20 and ST36 could further enhance the efficacy.

Combining mechanisms of black carbon and magnetic minerals in power plant fly ash.

Black carbon (BC), one of the pollutants emitted from fossil fuel combustion, is closely associated with minerals and other hazardous substances. To date, little is known about the mechanisms between BC and magnetic minerals. Accordingly, further investigating the association between magnetic minerals and BC is necessary. In this work, the extraction of BC from fly ash and the magnetic fraction from BC was achieved by flotation and magnetic separation, respectively. The morphology, mineralogical composition, and magnetic properties of BC and magnetic fraction were characterized by FTIR, XRD, SEM-EDS, and vibrating sample magnetometer (VSM). The results show that BC and magnetic minerals have similar mineral compositions, rich in quartz, mullite, magnetite, and hematite. The magnetic minerals have prominent spherical characteristics and are distributed on the surface and inside the pores of BC with irregular honeycomb features. The VSM and XRD analyses show that Fe3O4 is the primary magnetic material. Moreover, large amounts of C, O, and Fe around and on the surface of magnetic spheres were detected by EDS, indicating that the spherical particles may be the structure of BC-coated Fe3O4. Pyrolysis experiments showed that the yield of the magnetic fraction in the pyrolysis product reached 60 %, far exceeding the theoretical yield of 12 % based on 5 % of doped Fe. This further proves that Fe3O4 was combined with a large number of organics during its formation, which may be due to coating and chemical adsorption. Quantum chemical calculations also confirmed this chemical adsorption between Fe3O4 with BC based on density flooding theory, in which adsorption energies ranged from -213.374 KJ/mol to -827.741 KJ/mol.

Muse cells decrease the neuroinflammatory response by modulating the proportion of M1 and M2 microglia in vitro.

Neuroinflammation hinders repair of the central nervous system (CNS). Stem cell transplantation is a very promising approach for treatment of CNS injuries. However, it is difficult to select seed cells that can both facilitate nerve regeneration and improve the microenvironment in the CNS. In this study, we isolated multilineage-differentiating stress-enduring (Muse) cells from bone marrow mesenchymal stem cells. We explored the anti-inflammatory effect and mechanism of Muse cells in vitro by coculture of Muse cells with lipopolysaccharide-stimulated microglia. Our results showed that Muse cells effectively reduced the transcription and secretion of tumor necrosis factor α and interleukin-1ß and increased the expression of transforming growth factor-ß and interleukin-10 in microglia. In addition, Muse cells decreased the number of M1 microglia and increased the proportion of M2 microglia in an inflammatory environment more effectively than bone marrow mesenchymal stem cells. We also show that Muse cells inhibited the protein expression of toll-like receptor 4 (TLR4) and myeloid differentiation primary response protein (MyD88) and inhibited the expression of the phosphorylated forms of transcription factor p65, nuclear factor (NF)-κB inhibitor alpha, and p38 mitogen-activated protein kinase (MAPK) in microglia. Therefore, we suggest Muse cells cause antineuroinflammatory effects by inhibition of the TLR4/MyD88/NF-κB and p38 MAPK signaling pathways in microglia. Our results shed light on the function of Muse cells in relation to CNS diseases and provide insight into the selection of seed cells.

[Effects of elevated CO2 concentration, warming, and winter wheat planting on soil enzyme activities.] / CO2æµ“åº¦å‡é«˜ã€å¢žæ¸©å’Œå†¬å°éº¦ç§æ¤å¯¹åœŸå£¤é ¶æ´»æ€§çš„å½±å“.

Understanding the responses of soil enzyme activities to elevated CO2 concentration and warming can provide a scientific basis for nutrient management of croplands under global climate change. We conducted a pot expe-riment with climate chamber to examine the effects of elevated CO2 concentration and warming and winter wheat growth on soil enzyme activities. There were four climate scenarios: control (CK, 400 µmol·mol-1 CO2 concentration+normal ambient temperature), and CO2 concentration elevation (ECO2, 800 µmol·mol-1 CO2 concentration+normal ambient temperature), elevated temperature (ET, 400 µmol·mol-1 + temperature increased 4 ℃), and elevated CO2 concentration and temperature (ECO2+T, 800 µmol·mol-1 CO2 concentration + temperature increased 4 ℃). We measured the activities of soil ß-glucosidase (ßG), ß-N-acetyl glucosidase (NAG), alkaline phosphate (ALP) and polyphenol oxidase (PPO) at four growth stages (JS, jointing stage; AS, anthesis stage; FS, filling stage and MS, maturity stage), with and without winter wheat planting. Without winter wheat planting, there was no significant difference in four kinds of soil enzyme activities between ECO2 and CK, while ET and ECO2+T treatments had significant negative effect on soil enzyme activities. With winter wheat planting, compared with CK, ECO2 and ECO2+T treatments did not affect the activities of those four soil enzyme; but the ET treatment had great impact on soil ALP and PPO activities. The activities of four kinds of soil enzyme were significantly diffe-rent between the ET and ECO2+T treatments. Compared with ET treatment, ECO2+T treatment increased soil ßG activity at the JS, decreased NAG activity at the JS, increased ALP activity at both AS and FS, decreased PPO activity in the JS and increased in the AS. The interaction of elevated CO2 concentration and warming had significant effect on soil NAG and ALP activities with and without winter wheat planting. The interaction of warming and expe-rimental stage had significant effect on four kinds of soil enzyme activities without winter wheat planting, but the interaction of warming and crop growth stage had significant effect on ALP and PPO activities with winter wheat planting. The interaction of elevated CO2 concentration, warming and experimental period had significant effect on soil ßG, ALP and PPO activities without winter wheat growth, while with winter wheat growth, it had significant impact on NAG, ALP and PPO activities. The winter wheat growth had significantly inhibitory effect on ßG, NAG and ALP activities in the two early growth periods (JS+AS), significant promoting effect in the later growth periods (FS+MS), and significantly inhibitory effect on PPO activity during whole growth period. Overall, elevated CO2 concentration did not affect soil enzyme activities, while the elevation of CO2 concentration and temperature on soil enzyme activities differed among the soil enzymes at different growth stages. In addition, the responses of four soil enzyme activities to the interaction of elevated CO2 concentration and warming varied with and without winter wheat planting.

Dietary supplementation Eucommia ulmoides extract at high content served as a feed additive in the hens industry.

Since numerous natural components in Eucommia ulmoides belong to phytoestrogen, its effect on hens production deserve more attention. To investigate the potential of E. ulmoides extract used as a feed additive, laying performance, egg quality, yolk cholesterol, yolk fatty acids, yolk fatty, yolk volatile components, albumen amino acids, plasma biochemical parameters, intestinal histology, and gut microbiota of hens (n = 120) were determined between basal diet (A) and dietary supplementation low (B), middle (C), and high (D) level E. ulmoides extract for 11 wk. When compared to A group, 2 percentage points elevation in laying rate was observed of D group. Significant up-regulation of immunoglobulin indexes and down-regulation of lipid related indexes in D group were also found if comparison with A group, suggesting that supplementation E. ulmoides extract at a relative high content benefited in immunity enhancing and blood-fat depressing. Meanwhile, obvious variation in albumen amino acids and yolk volatile compounds were inspected as dietary supplementation E. ulmoides extract, especially in D group, implied that the flavor of egg would change under high-level E. ulmoides extract treatment. Besides, villus height and villus height to crypt depth ratio of duodenum, jejunum, and ileum in D group were also significantly higher than that of in A group, indicating high-level E. ulmoides extract contributed to nutrient adsorption via intestinal histology changing. Moreover, the richness, diversity, and composition of gut microbiota in D group also significantly altered with a comparison of A group. These variation caused gut microbiota in D group major enriched in the KEGG pathway of insulin signing pathway, systemic lupus erythematosus, and bacterial invasion of epithelial cells, which were conducive to egg production elevation via facilitating nutrient adsorption, inflammation relieving, blood lipid amelioration, and insulin resistance alleviation. These results indicated that dietary supplementation E. ulmoides extract at high content could serve as a feed additive in the hens industry.

Lipoxin A4 methyl ester protects PC12 cells from ketamine-induced neurotoxicity via the miR-22/BAG5 pathway.

OBJECTIVE: Ketamine is an anesthetic that induces neurotoxicity when administered at high doses. In this work, we explored the protective effects of lipoxin A4 methyl ester (LXA4 ME) against ketamine-induced neurotoxicity and the underlying protective mechanism in pheochromocytoma (PC12) cells. METHODS: PC12 cells were treated with 50 µM of ketamine and different LXA4 ME concentrations of LXA4 ME (5-50 nM) for 24 h, and their viability, apoptosis, and oxidative status were assessed. RESULTS: Quantitative real-time polymerase chain reaction experiments showed that ketamine downregulated miR-22 expression and upregulated Bcl-2-associated athanogene 5 (BAG5) in PC12 cells in a concentration-dependent manner. LXA4 ME induced the opposite effects, thus attenuating ketamine-induced neurotoxicity. Further in vitro assays showed that miR-22 directly targeted BAG5, thus promoting cell viability by suppressing cell apoptosis and oxidative stress. Under expression miR-22 or upregulation of BAG5 antagonized the effects of LXA4 ME. CONCLUSION: LXA4 ME can protect PC12 cells from ketamine-induced neurotoxicity by activating the miR-22/BAG5 signaling pathway. Thus, LXA4 ME can be used as a protective drug against ketamine-induced neural damage.

Longitudinal Capsulotomy in Hip Arthroscopy: A Safe and Feasible Procedure for Cam-Type Femoracetabular Impingement.

OBJECTIVE: To evaluate the surgical security, feasibility, and clinical efficacy of the longitudinal outside-in capsulotomy in hip arthroscopic treatment for cam-type femoracetabular impingement (FAI). METHODS: We retrospectively reviewed patients with cam-type FAI who underwent hip arthroscopy in our institute from January 2018 to June 2019. All hip arthroscopic procedures were performed by one experienced surgeon in the same manner, except the fashions of capsulotomy. Fifty six patients with mean age of 39.1 and mean body mass index (BMI) of 24.5 were categorized into two groups according to the fashions of capsulotomy. Twenty six cases with longitudinal outside-in capsulotomy were categorized into Group L, and 30 cases with transversal interportal capsulotomy were categorized into Group T as the control group. The demographic parameters were retrieved from medical documents and compared between the two groups. Surgical outcome including overall surgical time, traction time, complications, visual analogue score (VAS), and intraoperative radiation exposure were compared to investigate the security and feasibility. Radiographic assessment, and functional outcome were compared between the two groups to determine the clinical efficacy of the longitudinal capsulotomy. RESULTS: There was no significant difference in the demography and duration of follow-up between the two groups. The overall surgical time demonstrated no significant difference between Group L and Group T (130.8 ± 16.6 min and 134.0 ± 14.7 min, P = 0.490). Significantly decreased traction time was found in Group L (43.2 ± 8.4 min and 62.2 ± 8.6 min, P < 0.001) compared to Group T. The Median of the fluoroscopic shot was 1 and 3 (P < 0.001). No major complications and reoperation were reported in both groups. The case of intraoperative iatrogenic injure was 0 (0%) and 6 (20%) in Group L and Group T respectively (P = 0.035), and the case of postoperative neurapraxia was 0 (0%) and 8 (26.6%) in Group L and Group T respectively (P = 0.017). The Median of postoperative VAS was 2 and 3 in Group L Group T (P = 0.002). The postoperative α angle was 42.3° ± 3.4° and 44.4° ± 3.5° in group L and group T respectively (P = 0.001). The postoperative iHOT-12 score at final follow-up was 79.3 ± 6.7 and 77.0 ± 7.9 respectively (P = 0.141). CONCLUSION: Longitudinal outside-in capsulotomy with less radiation exposure, reduced traction time, and reduced complications could be a safe and feasible procedure in arthroscopic treatment for cam FAI. Its clinical efficacy was not worse compared with traditional interportal capsulotomy in short-term follow-up.

Speckle-Free SAR Image Ship Detection.

Ship detection is one of important applications for synthetic aperture radar (SAR). Speckle effects usually make SAR image understanding difficult and speckle reduction becomes a necessary pre-processing step for majority SAR applications. This work examines different speckle reduction methods on SAR ship detection performances. It is found out that the influences of different speckle filters are significant which can be positive or negative. However, how to select a suitable combination of speckle filters and ship detectors is lack of theoretical basis and is also data-orientated. To overcome this limitation, a speckle-free SAR ship detection approach is proposed. A similar pixel number (SPN) indicator which can effectively identify salient target is derived, during the similar pixel selection procedure with the context covariance matrix (CCM) similarity test. The underlying principle lies in that ship and sea clutter candidates show different properties of homogeneity within a moving window and the SPN indicator can clearly reflect their differences. The sensitivity and efficiency of the SPN indicator is examined and demonstrated. Then, a speckle-free SAR ship detection approach is established based on the SPN indicator. The detection flowchart is also given. Experimental and comparison studies are carried out with three kinds of spaceborne SAR datasets in terms of different polarizations. The proposed method achieves the best SAR ship detection performances with the highest figures of merits (FoM) of 97.14%, 90.32% and 93.75% for the used Radarsat-2, GaoFen-3 and Sentinel-1 datasets, accordingly.

Preventive electroacupuncture ameliorates D-galactose-induced Alzheimer's disease-like inflammation and memory deficits, probably via modulating the microbiota-gut-brain axis.

OBJECTIVES: We aimed to observe the effects of preventive electroacupuncture (EA) on the microbiota-gut-brain axis and spatial learning and memory deficits and to investigate the possible mechanism using D-galactose (D-gal)-induced aging rats. MATERIALS AND METHODS: D-gal was intraperitoneally injected to establish the aging model. We used Morris water maze to detect spatial learning and memory function of rats. RT-PCR was applied to test targeted gut microbes. The expression of zonula occludens-1 (ZO-1) and Toll-like receptor 4 (TLR4)/nuclear factor (NF)-κB pathway proteins were detected by Western blotting. ELISA was employed to evaluate the level of lipopolysaccharides (LPS), diamine oxidase (DAO) and S-100ß. Additionally, we observed ionized calcium-binding adapter molecule-1 (Iba-1) expression in the hippocampal CA1 area by immunofluorescence. RESULTS: Morris water maze test showed decreased mean escape latency and increased target quadrant time after EA treatment. The gut microbiota composition has been modified in EA treated rats. Molecular examination indicated that expression of ZO-1 was improved and the the concentration of LPS in blood and hippocampus were reduced in EA treated rats. Further, we observed an inhibition of activated microglia and TLR4/NF-κB pathway in EA groups. CONCLUSION: Preventive EA may alleviate the impairments of the microbiota-gut-brain axis and spatial learning and memory in aging, and the mechanism may be related to the inhibition of TLR4/NF-kB signaling pathway. The combination of acupoints GV20 and ST36 can enhance the therapeutic effect in aging rats.

The enantiomer-selective metabolism of hexabromocyclododecanes (HBCDs) by human HepG2 cells.

Although hepatic metabolism of hexabromocyclododecanes (HBCDs) played critical roles in the selective bioaccumulation of HBCDs in humans, the hepatic metabolism patterns of its enantiomers remained ambiguous. Aiming to elucidate the mechanism on hepatic metabolism of hexabromocyclododecanes (HBCDs) enantiomers, the enantiomers ((+)-α-HBCD, (-)-α-HBCD, (+)-γ-HBCD, and (-)-γ-HBCD), the diastereoisomers (α-, ß-, and γ-HBCDs) and the mixed of α- and γ-HBCDs were incubated with human HepG2 cell under different exposure levels in the present study. The clearance percentages ranked as γ-HBCD enantiomers >ß-HBCD enantiomers >α-HBCD enantiomers at the same exposure levels. The clearance percentages of (+)- and (-)-α-HBCDs increased when cells were exposed to racemic α-HBCD and the mixture of racemic α- and γ-HBCDs (p < 0.05). (-)-γ-HBCD was more resistant to human hepatic metabolism than (+)-γ-HBCD, leading to the enantiomer fractions (EFs) of γ-HBCD lower than 0.50. (-)-α-HBCD was slightly more metabolized when independently exposed to α-HBCD, while (+)-α-HBCD was more preferentially metabolized after exposure to α- and γ-HBCD mixtures. Hydroxylation and debromination HBCD metabolites were identified. In addition, the different EFs of HBCDs in cells and mediums suggested the selective transfer of chiral HBCDs and HBCD metabolites through the cell membrane. This study provided new insight into the enantiomer-selective metabolism of HBCDs.

Acupuncture and Related Therapies for the Cognitive Function of Alzheimer's Disease: A Network Meta-Analysis.

Background: Acupuncture and acupuncture-related therapies are effective for Alzheimer's disease (AD), therefore, we aimed to compare and rank the interventions that mainly focus on acupuncture-related therapies in the treatment of patients with mild to moderate AD. Methods: We used network meta-analysis to evaluate the direct and indirect evidence shown in randomized controlled trials of AD. The data were analyzed using RavMan manager, Stata, and WinBUGS software after two researchers independently screened the literature, extracted the data, and assessed the risk of bias in the included studies. Results: We analyzed a total of 36 eligible studies, including 2712 patients, involving 14 types of acupuncture-related therapies and comprehensive therapies. For Mini-Mental State Examination (MMSE), acupuncture (ACU) combined with cognitive and memory training (Training) was more effective than ACU, ACU+Chinese herb (CH), ACU+Donepezil (DON), CH, DON, DON+Nimodipine (NIM), Music therapy (Music), NIM, Placebo, and Training (P<0.05), while ACU+CH was batter than CH (P<0.05), and ACU+DON+NIM was better than DON+NIM (P<0.05). For Alzheimer's Disease Assessment Scale-Cognitive section (ADAS-cog), ACU was more effective than DON and placebo (P<0.05). For Activities of Daily Living (ADL), ACU+DON was better than CH, DON, NIM, and Placebo (P<0.05). For the clinical effectiveness rate, ACU, ACU+CH, ACU+CH+DON, ACU+CH+DON+NIM, ACU+DON, CH, NIM were all more effective than DON+NIM (P<0.05), while ACU and ACU+CH were better than DON (P<0.05). The comprehensive ranking results show that ACU+training and ACU have the highest ranking probability. Conclusion: ACU+Training and ACU may be the best therapies to improve the cognitive function of patients with mild to moderate AD, while the combination of acupuncture-related therapies and other therapies has a higher overall benefit.

Preventive electroacupuncture reduces cognitive deficits in a rat model of D-galactose-induced aging.

Acupuncture can reduce cognitive deficits in Alzheimer's disease. However, whether electroacupuncture can prevent or alleviate the cognitive deficits in animal models of aging remains poorly understood. Studies have shown that disordered epigenetic modifications play a critical role in age-related cognitive decline. Therefore, we hypothesized that preventive electroacupuncture might improve cognitive functions during aging by regulating epigenetic modifications. A rat model of aging was produced by intraperitoneal injection of 120 mg/kg D-galactose for 8 weeks. Baihui and Shenshu acupoints were stimulated by electroacupuncture for 8 weeks from the first day of D-galactose administration. Preventive electroacupuncture alleviated memory impairment, decreased tau hyperphosphorylation, and reduced glycogen synthase kinase-3ß protein and mRNA expression levels in the brainstem dorsal raphe nucleus, where intracellular neurofibrillary tangle lesions first occur. In addition, the DNA methylation level in the promoter region of the glycogen synthase kinase-3ß gene was increased. The effects of preventive electroacupuncture were stronger than those of preventive acupuncture. Intraperitoneal injection of 0.4 mg/kg 5-aza-2'-deoxycytidine, an inhibitor of DNA methyltransferase that blocks epigenetic modifications, antagonized the effects of preventive electroacupuncture. Our results suggest that preventive electroacupuncture treatment alleviates cognitive impairment in aging rats probably by affecting the epigenetic modification of the glycogen synthase kinase-3ß gene in the dorsal raphe nucleus. This study was approved by the Animal Ethics Committee of Hubei University of Chinese Medicine, China (approval No. HUCMS201712001) on November 28, 2017.

Acupuncture and related therapies for hyperlipidemia: A protocol for systematic review and network meta-analysis.

OBJECTIVE: To compare and rank the clinical effects of different acupuncture and acupuncture-related therapies on patients with hyperlipidemia. METHODS: We used Network Meta-Analysis (NMA) to evaluate the direct and indirect evidence from relevant studies. Three English and 4 Chinese databases were searched to collect randomized controlled trials (RCT) of acupuncture and related therapies in the treatment of hyperlipidemia. The data were analyzed using Stata15.0 and WinBUGS1.4.3 software after 2 researchers independently screened the literature, extracted the data, and assessed the risk of bias in the included studies. RESULTS: Based on the current evidence, we comprehensively compare the pros and cons of various acupuncture-related therapies, rank the efficacy of various acupuncture-related therapies compared with statins in the treatment of hyperlipidemia, and summarize the best acupuncture intervention methods or combinations. CONCLUSION: This study will provide new evidence for the safety and effectiveness of acupuncture-related therapies in the treatment of hyperlipidemia, and may be helpful for clinicians, hyperlipidemia patients, and clinical guideline makers to choose the optimal combination of acupuncture for the treatment of hyperlipidemia. REGISTRATION NUMBER: INPLASY2020100100.