[Heat-sensitive moxibustion for migraine without aura: a randomized controlled trial].

OBJECTIVE: To compare the clinical effect between heat-sensitive moxibustion and mild moxibustion for migraine without aura. METHODS: A total of 54 patients with migraine without aura were randomized into an observation group (27 cases, 2 cases dropped off) and a control group (27 cases, 2 cases dropped off). The basic western medication treatment was adopted in the two groups. In the control group, mild moxibustion was applied at Shuaigu (GB 8), Fengchi (GB 20) and Yanglingquan (GB 34) on the affected side. In the observation group, the frequent acupoint areas of the affected side i.e. Shuaigu (GB 8), Fengchi (GB 20), Taiyang (EX-HN 5), Taichong (LR 3), Yanglingquan (GB 34) were determined, 3 acupoints with strong heat-sensitive sensation were selected each time and mild moxibustion was adopted. The treatment was given once a day, 5 times of treatment was as one course and 2 courses were required in the two groups. Before and after treatment, the scores of migraine symptom, visual analogue scale (VAS), migraine specific quality of life questionnaire (MSQ) were observed, and the clinical efficacy was evaluated after treatment in the two groups. RESULTS: After treatment, the scores of migraine symptom and VAS were decreased compared with those before treatment (P<0.01), while the MSQ scores were increased compared with those before treatment (P<0.01) in the two groups. After treatment, the scores of migraine symptom and VAS in the observation group were lower than those in the control group (P<0.05), while the MSQ score in the observation group was higher than that in the control group (P<0.01). The total effective rate was 92.0% (23/25) in the observation group, which was superior to 72.0% (18/25) in the control group (P<0.05). CONCLUSION: Both heat-sensitive moxibustion and mild moxibustion can effectively alleviate the clinical symptoms, improve the headache degree and life quality in patients with migraine without aura, the clinical efficacy of heat-sensitive moxibustion is superior to that of mild moxibustion.

Polarization Switching and Correlated Phase Transitions in Fluorite-Structure ZrO2 Nanocrystals.

Unconventional ferroelectricity in fluorite-structure oxides enables tremendous opportunities in nanoelectronics owing to their superior scalability and silicon compatibility. However, their polarization order and switching process remain elusive due to the challenges of visualizing oxygen ions in nanocrystalline films. In this work, the oxygen shifting during polarization switching and correlated polar-nonpolar phase transitions are directly captured among multiple metastable phases in freestanding ZrO2 thin films by low-dose integrated differential phase-contrast scanning transmission electron microscopy (iDPC-STEM). Bidirectional transitions between antiferroelectric and ferroelectric orders and interfacial polarization relaxation are clarified at unit-cell scale. Meanwhile, polarization switching is strongly correlated with Zr-O displacement in reversible martensitic transformation between monoclinic and orthorhombic phases and two-step tetrahedral-to-orthorhombic phase transition. These findings provide atomic insights into the transition pathways between metastable polymorphs and unravel the evolution of polarization orders in (anti)ferroelectric fluorite oxides.

Associations of blood metals with liver function: Analysis of NHANES from 2011 to 2018.

BACKGROUND: Heavy metals have been reported to affect liver function. However, there is currently little and inconsistent knowledge about the effects of combined and individual blood metals on specific parameters of liver function in the general population. Hence, this study aimed to elucidate their associations. METHODS: Data from National Health and Nutrition Examination Survey (NHANES) 2011-2018 were used in this cross-sectional study. Multivariate linear, and a quantile-based g-computation (qgcomp) were applied to explore the associations between blood metals [mercury (Hg), manganese (Mn), lead (Pb), cadmium (Cd), selenium (Se)], alone and in combination, and liver function parameters [alanine transaminase (ALT), aspartate transaminase (AST), ALT/AST, alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT) and serum total bilirubin (TBIL)]. RESULTS: A total of 15,328 were included. Multivariate linear models indicated that liver function was significantly associated with blood heavy metals. The most significant relationship was found between Se and AST (ß 5.09, 95%CI (3.28,6.91), p＜0.001), Mn and ALT (ß 1.24, 95%CI (0.57, 1.91), p＜0.001). Furthermore, the qgcomp analysis showed that the combination of five blood metals was positively associated with AST, ALT, GGT, TBIL and HSI. Cd contributed the most to the correlation of AST (weight = 0.447), Se contributed the most to the association of ALT (weight = 0.438) and HSI (weight = 0.570), Pb contributed the most to the association of GGT (weight = 0.421) and Hg contributed the most to the correlation of TBIL (weight = 0.331). CONCLUSIONS: Blood heavy metal levels were significantly associated with liver function parameters. Further studies are required to clarify the relationship between heavy metals and liver function.

[Proteomics analysis of Astragalus polysaccharide on TLR4-activated lung cancer cell-derived exosomes].

Astragalus polysaccharide(APS), one of the main active components of Astragali Radix, plays an anti-tumor effect by regulating the inflammatory microenvironment of tumors. Exosomes are small extracellular vesicles with a diameter ranging from 50 to 200 nm and carry several biological components from parental cells such as nucleic acids and proteins. When combined with recipient cells, they play an important role in intercellular communication and immune response. In this study, exosomes released from H460 cells at the inflammatory state or with APS addition activated by Toll-like receptor 4(TLR4) were extracted by ultracentrifugation and characterized by Western blot, transmission electron microscopy, and nanoparticle tracking analysis. The exosomal proteins derived from H460 cells in the three groups were further analyzed by label-free proteomics, and 897, 800, and 911 proteins were identified in the three groups(Con, LPS, and APS groups), 88% of which belonged to the ExoCarta exosome protein database. Difference statistical analysis showed that the expression of 111 proteins was changed in the LPS group and the APS group(P<0.05). The biological information analysis of the differential proteins was carried out. The molecular functions, biological processes, and signaling pathways related to the differential proteins mainly involved viral processes, protein binding, and bacterial invasion of proteasome and epithelial cells. Key differential proteins mainly included plasminogen activator inhibitor-1, laminin α5, laminin α1, and CD44, indicating that tumor cells underwent systemic changes in different states and were reflected in exosomes in the inflammatory microenvironment. The analysis results also suggested that APS might affect the inflammatory microenvironment through the TLR4/MyD88/NF-κB signaling pathway or the regulation of the extracellular matrix. This study is conducive to a better understanding of the mechanism of tumor development in the inflammatory state and the exploration of the anti-inflammatory effect of APS at the exosome level.

Sodium-calcium exchanger isoform-3 targeted Withania somnifera (L.) Dunal therapeutic intervention ameliorates cognition in the 5xFAD mouse model of Alzheimer's disease.

The third isoform of the Na+-Ca2+ exchanger (NCX3) is crucial for a physiological fine-tuning of the Ca2+ fluxes in excitable tissues. In this view, the NCX3 accounts for the aberrant Ca2+ influx seen during neuronal excitotoxicity, such as in Alzheimer's disease (AD). However, little is known about NCX3 regulation and functional properties. Withania somnifera (L.) Dunal (W. somnifera), a traditional indigenous plant widely recognized for having numerous medicinal values, was undertaken to determine its potential therapeutic benefit against aggregated Aß1-42-induced NCX3 dysregulation and the thereof cognition impairment in 5xFAD mice. The undertaken sourced dried roots of authenticated W. somnifera physicochemical compositional tests satisfied standards of pharmacognostic quality, and further phytochemical analysis of the roots methanol extract revealed the roots constitute several antioxidants. Following an intra-gastric gavage administration of synthesized W. somnifera roots methanolic extract from postnatal day 30 (P30) to P75, in vivo cognitional studies and then neurochemical examinations of the NCX3 expression level, Aß plaque deposition, and antioxidant activities in the AD-associated brain regions of 4-month-old 5xFAD mice suggests that the oxidative stress normalizing effects of W. somnifera constituents, operating on the NCX3, may have a therapeutic role in the improvement of cognition in AD.

Migration and transformation of heavy metals in hyperaccumulators during the thermal treatment: a review.

The pollution of heavy metals (HMs) in the soil has become one of the important factors affecting the national environment and human health. Phytoremediation, as a technology to deal with HM pollution in soil, has been extensively studied and applied due to its sustainability and environmental friendliness. However, hyperaccumulators polluted by HMs need to be properly treated to avoid secondary pollution to the environment. This paper reviews the migration and transformation of HMs during the incineration, pyrolysis, gasification, and hydrothermal treatment of hyperaccumulators; comprehensively evaluates the advantages and disadvantages of each technology in the treatment of HM-enriched hyperaccumulators; and analyzes the current development status and unsolved problems in detail for each technology. Generally speaking, thermal treatment technology can fix most of the HMs of exchangeable fraction in biochar, reducing its bioavailability and biotoxicity. In addition, the application direction and research focus of the target product are discussed, and it is clarified that in the future, it is necessary to further optimize the reaction conditions and explore the mechanism of HM immobilization to maximize the immobilization of HMs and improve the quality and output of the target product.

Highly Efficient Water-Soluble Photosensitizer Based on Chlorin: Synthesis, Characterization, and Evaluation for Photodynamic Therapy.

The clinical applications of many photosensitizers (PSs) are limited because of their poor water solubility, weak tissue penetration, low chemical purity, and severe toxicity in the absence of light. We designed a novel chlorin-based PS (designated as HPS) to achieve fluorescence image-guided photodynamic therapy (PDT) with efficient ROS generation. In addition to its simple fabrication process, HPS has other advantages such as excellent water solubility, strong NIR absorption, and high biocompatibility upon chemical functionalization for enhanced phototherapy. HPS exhibited high photodynamic performance against lung cancer and breast cancer cells by generating a large amount of singlet oxygen (1O2) under 654 nm laser irradiation. HPS accumulated into multiple organelles such as mitochondria and the endoplasmic reticulum and triggered cell apoptosis by laser exposure. In the tumor-bearing mice, in vivo, HPS showed an optimal half-life in circulation and achieved fluorescence-image-guided PDT within the irradiation window, resulting in effective tumor growth inhibition and the prolonged survival of animals. Moreover, the antitumor PDT effect of HPS was close to the clinical trial phase II stage of HPPH even at the low dosage of 0.32 mg/kg (under 75 J/cm2 laser), while the systemic safety of HPS was much higher. In conclusion, HPS is a novel water-soluble chlorin derivative with excellent PDT potential for clinical transformation.

[Spatiotemporal Variations in Nutrient Loads in River-lake System of Changdang Lake Catchment in 2016-2017].

Eutrophication of shallow lakes in the middle and lower reaches of the Yangtze River has become an increasingly serious problem. In this study, we investigated the temporal and spatial variations in nutrient loads (nitrogen, N and phosphorus, P) in the Changdang Lake Catchment located to the northwest of Lake Taihu through field sampling and laboratory analysis in 2016-2017. The results show the severity of the N and P pollution in the Changdang Lake catchment. The mean river water concentrations of TN, NO3--N, NH4+-N, TP, Chla, and permanganate index are (3.70±0.76) mg ·L-1, (1.81±0.42) mg ·L-1, (1.03±0.61) mg ·L-1, (0.38±0.31) mg ·L-1, (25.74±37.00) µg ·L-1, and (6.35±0.81) mg ·L-1, respectively. N pollution in the river is more severe in winter and spring than in summer and autumn whereas P pollution in the river is worse in autumn and winter than in spring and summer. Spatially, the magnitude of river N and P pollution follows the order of northern > northwestern > southern > eastern part of the study area. The rivers are in a state of moderate to severe eutrophication. The mean lake water concentrations of TN, NO3--N, NH4+-N, TP, Chla, and permanganate index are (2.25±0.94) mg ·L-1, (0.98±0.47) mg ·L-1, (0.19±0.14) mg ·L-1, (0.11±0.03) mg ·L-1, (18.71±8.76) µg ·L-1, and (4.59±1.09) mg ·L-1, respectively. The water quality in Changdang Lake is categorized as worse than class Ⅲ for TN and TP concentrations, which show decreasing trends from the west to the east to the south of the lake. The lake is in a status of slight to moderate eutrophication. The lake water quality is affected by the combination of sewage discharge and non-point source pollutant losses. The inflow rivers including the Danjinlicao River, Tongji River, and Xuebu River are the dominant pollution sources for Changdang Lake. The Danjinlicao River transports 10-12 times the total N and P loads transported by Tongji and Xuebu rivers. Changes in land use and atmospheric deposition are the driving factors of the deterioration of water quality and eutrophication in the catchment.

The GLP-1 receptor herbal agonist morroniside attenuates neuropathic pain via spinal microglial expression of IL-10 and ß-endorphin.

OBJECTIVES: To assess the protective effect of the glucagon-like peptide-1 receptor (GLP-1R) agonist morroniside against neuropathic pain and its downstream mechanisms of activating microglial GLP-1R/interleukin-10 (IL-10)/ß-endorphin antinociceptive pathway. METHODS: Spinal nerve ligation-induced neuropathic pain rats were intrathecally injected with morroniside, with mechanical paw withdrawal threshold being assessed. The expression of spinal and cultured microglia IL-10 and ß-endorphin were detected with qRT-PCR. KEY FINDINGS: Morroniside alleviated mechanical allodynia in neuropathic rats, which was blocked by inhibiting or depleting microglia. In addition, neutralizing spinal IL-10 or ß-endorphin with specialized antibodies or blocking the µ-opioid receptor was able to fully reverse the morroniside-induced mechanical antiallodynia. Morroniside treatment stimulated the gene expression of IL-10 and ß-endorphin in the spinal lumbar enlargements of neuropathic rats as well as in primary cultured microglia. Furthermore, pretreatment with the IL-10 antibody blocked morroniside-stimulated ß-endorphin expression in the spinal cords of neuropathic rats and cultured primary microglia, whereas the ß-endorphin antibody failed to affect morroniside-stimulated gene expression of IL-10. CONCLUSIONS: These results reveal that morroniside produces therapeutic effects in neuropathy through spinal microglial expression of IL-10 and subsequent ß-endorphin after activation of GLP-1R.

Concurrent bullatine A enhances morphine antinociception and inhibits morphine antinociceptive tolerance by indirect activation of spinal κ-opioid receptors.

ETHNOPHARMACOLOGICAL RELEVANCE: Bullatine A, a C20-diterpenoid alkaloid and one of the major effective ingredients in Aconiti brachypodi Radix (Xue-shang-yi-zhi-hao), can block pain hypersensitivity in a variety of rodent models through expression of spinal microglial dynorphin A. AIM OF THE STUDY: To assess the interaction between bullatine A and morphine on antinociception in acute nociception and pain hypersensitivity states, with the exogenous synthetic dynorphin A as a comparison MATERIALS AND METHODS: Spinal nerve ligation-induced neuropathic rats and naïve mice were used for assessing the acute and chronic interactions of bullatine A/dynorphin A with morphine. RESULTS: Single subcutaneous injection of bullatine A or dynorphin A(1-17) did not either alter formalin- and thermally (hot-plate and water immersion tests)-induced acute nociception or potentiate morphine antinociception in naïve mice. In contrast, bullatine A dose-dependently inhibited formalin-induced tonic pain with the efficacy of 54% inhibition and the half-effective dose of 0.9mg/kg. Concurrent bullatine A additively enhanced morphine antinociception. In neuropathic rats, the antinociceptive effects of multiple bidaily intrathecal injections of bullatine A and dynorphin A remained consistent over 13 days, whereas morphine produced progressive and complete tolerance to antinociception, which was completely inhibited by concurrent bullatine A and dynorphin A. A single intrathecal injection of bullatine A and dynorphin A immediately reversed established morphine tolerance in neuropathic rats, although the blockade was a less degree in the thermally induced mouse acute nociceptive tests. The inhibitory effects of bullatine A and dynorphin A on morphine tolerance were immediately and completely attenuated by intrathecal dynorphin A antibody and/or selective κ-opioid receptor antagonist GNTI. CONCLUSION: These results suggest that bullatine A produces antinociception without induction of tolerance and inhibits morphine antinociceptive tolerance, and provide pharmacological basis for concurrent bullatine A and morphine treatment for chronic pain and morphine analgesic tolerance.

Dietary mustard seeds (Sinapis alba Linn) suppress 1,2-dimethylhydrazine-induced immuno-imbalance and colonic carcinogenesis in rats.

In a Wistar rat model, prolonged supplementation of mustard seed (MS) to the diet significantly ameliorates the induction of colorectal carcinomas by 1,2-dimethylhydrazine (DMH). The expression of the splenocyte major histocompatibility complex class I (MHCI) was found significantly enhanced, whereas that of the major histocompatibility complex class II (MHCII) was significantly decreased. Compared to that of control animals, the proportion of spleenic B- and dendritic cells (DC) was amplified in the MS group. The expressions of MHCI, as well as that of MHCII, were increased in DC cells; whereas in B cells, MHCI expression was augmented but that of MHCII moderately decreased. The percentages of CD8+CD28+ and CD4+CD28+ cells were increased in the MS group, while the CD4+CD25+Foxp3+ subset was depressed. Plasma analysis showed that DMH-exposure induced amplified amounts of interleukin (IL)-4, IL-5, IL-10, and transforming growth factor-beta, whereas MS feeding counteracted this effect but enhanced IL-2, IL12p70, IL21, TNF-alpha, and interferon-gamma. In the SW480 colon adenocarcinoma cell-line, the cytotoxicity of spleenic T-cells from MS-fed animals was significantly increased. In the DMH-exposed rats, the expression of perforin in the spleenic T-cells was dramatically decreased, whereas MS abolished this depression. In summary, dietary MS suppresses DMH-induced immuno-imbalance as well as colon carcinogenesis in rats.