Danggui Shaoyao San and disassembled prescription: neuroprotective effects via AMPK/mTOR-mediated autophagy in mice.

BACKGROUND: Danggui Shaoyao San (DSS), a frequently prescribed Chinese medicine formula, has demonstrated clinical efficacy in the treatment of Alzheimer's disease (AD). This study aims to explore the differences in therapeutic effects of DSS and its disassembled prescriptions, Suangan (SG) and Xingan (XG), in treating Alzheimer's Disease and the mechanism of DSS recovering autophagy in AD. METHODS: A network pharmacology strategy was employed to delineate the bioactive constituents, associated targets, and regulatory mechanisms of DSS in AD, encompassing in silico target forecasting, the generation and scrutiny of PPI networks, alongside GO and KEGG-based pathway elucidation. An AD mouse model, induced by intracerebroventricular injection of Aß1-42, was used to evaluate the therapeutic effects of DSS and its disassembled prescriptions on AD. Cognitive function was evaluated using the Morris water maze. Expression levels of inflammatory cytokines were quantified via RT-qPCR and ELISA. Western blotting was used to detect the expression of proteins related to AD pathological markers and the AMPK/mTOR signaling pathway. RESULTS: 50 active compounds and 718 HUB genes were screened from relevant databases and literature. KEGG and GO analyses indicated that DSS's potential mechanisms against AD involved the AMPK/mTOR signaling pathway and mitophagy. In vivo animal model, the results demonstrated that DSS, SG, and XG treatments improved cognitive function and ameliorated neuroinflammation in mice. Additionally, they alleviated the pathological changes of neuronal cells. These treatments also increased the protein level of PSD-95, and decreased levels of APP and p-Tau. Among them, DSS exhibited the best efficacy. Furthermore, DSS, SG, and XG upregulated the expression of LC3, Beclin1, and p-AMPK, while decreasing the expression of P62 and p-mTOR. CONCLUSIONS: DSS, SG, and XG were found to ameliorate AD-related pathological symptoms in Aß1-42-injected mice, likely through the AMPK/mTOR autophagy signaling pathway.

The effect and mechanism of patchouli alcohol on cognitive dysfunction in AD mice induced by Aß1-42 oligomers through AMPK/mTOR pathway.

Alzheimer's disease (AD) is a neurodegenerative brain disorder that progressively impairs long-term and working memory. The function and mechanism of PA(Patchouli alcohol) in improving AD in the external treatment of encephalopathy remain unclear. This study aimed to investigate the therapeutic effect of PA on AD using an Aß1-42 induced AD mouse model with LPS(Lipopolysaccharide) stimulation of BV2 microglial cells. Additionally, we aimed to explore the potential mechanism of PA in enhancing autophagy and reducing neuroinflammation through the AMPK (AMP-activated protein kinase)/mTOR (Mammaliam target of rapamycin) signaling pathway. The Morris water maze was used to assess cognitive function, and cortical and hippocampal tissues were collected for further analysis of the corresponding signaling pathways and inflammatory changes through biological experiments. Our research findings demonstrate that PA has a significant positive impact on cognitive and memory impairments in mice that have been induced with Aß1-42-induced AD. Additionally, PA was also found to revert the activation of microglia induced by LPS. These effects may be attributed to the reduction of neuroinflammation and enhancement of the AMPK/mTOR autophagy pathway. Therefore, PA may serve as an effective therapeutic option to prevent or delay the progression of AD-associated memory dysfunction.

13C6-Glucose Labeling Associated with LC-MS: Identification of Plant Primary Organs in Secondary Metabolite Synthesis.

This paper presents a novel and efficient method for certifying primary organs involved in secondary metabolite synthesis. As the most important secondary metabolite in Parispolyphylla var. yunnanensis (Franch.) Hand. -Mzt. (PPY), Paris saponin (PS) has a variety of pharmacological activities and PPY is in increasing demand. This study established leaf, rhizome, and stem-vascular-bundle 13C6-Glucose feeding and non-feeding four treatments to precisely certify the primary organs involved in Paris saponins VII (PS VII) synthesis. By combining liquid chromatography-mass spectrometry (LC-MS), the 13C/12C ratios of leaf, rhizome, stem, and root in different treatments were quickly and accurately calculated, and four types of PS isotopic ion peak(M-) ratios were found: (M+1) -/M-, (M+2) -/M-, (M+3) -/M- and (M+4) -/M-. The results showed that the ratio of 13C/12C in the rhizomes of the stem-vascular-bundle and rhizome feeding treatments was significantly higher than that in the non-feeding treatment. Compared to the non-feeding treatment, the ratio of PS VII molecules (M+2) -/M- in the leaves increased significantly under leaf and stem-vascular-bundle feeding treatments. Simultaneously, compared to the non-feeding treatment, the ratio of PS VII molecules (M+2) -/M- in the leaves under rhizome treatment showed no significant difference. Furthermore, the ratio of PS VII molecules (M+2) -/M- in the stem, root, and rhizome showed no differences among the four treatments. Compared to the non-feeding treatment, the ratio of the Paris saponin II (PS II) molecule (M+2) -/M- in leaves under leaf feeding treatment showed no significant difference, and the (M+3) -/M- ratio of PS II molecules in leaves under leaf feeding treatment were lower. The data confirmed that the primary organ for the synthesizing of PS VII is the leaves. It lays the foundation for future identification of the primary organs and pathways involved in the synthesis of secondary metabolites in medicinal plants.

Development of a colloidal gold immunochromatographic strip for rapid detection of avian coronavirus infectious bronchitis virus.

Avian infectious bronchitis virus (IBV) still causes serious economic losses in the poultry industry. Currently, there are multiple prevalent genotypes and serotypes of IBVs. It is imperative to develop a new diagnosis method that is fast, sensitive, specific, simple, and broad-spectrum. A monoclonal hybridoma cell, N2D5, against the IBV N protein was obtained after fusion of myeloma SP2/0 cells with spleen cells isolated from the immunized Balb/c mice. The N2D5 monoclonal antibody (mAb) and the previously prepared mouse polyclonal antibody against the IBV N protein were used to target IBV as a colloidal gold-mAb conjugate and a captured antibody, respectively, in order to develop an immunochromatographic strip. The optimal pH and minimum antibody concentration in the reaction system for colloidal gold-mAb N2D5 conjugation were pH 6.5 and 30 µg/mL, respectively. Common avian pathogens were tested to evaluate the specificity of the strip and no cross-reaction was observed. The sensitivity of the strip for detecting IBV was 10-1.4522 EID50/mL. The strip showed a broad-spectrum cross-reactive capacity for detecting IBV antigens, including multiple IBV genotypes in China and all of the seven serotypes of IBV that are currently prevalent in southern China. Additionally, the result can be observed within 2 min without any equipment. The throat and cloacal swab samples of chickens that were artificially infected with three IBV strains were tested using the developed strip and the qPCR method; the strip test demonstrated a high consistency in detecting IBV via qPCR gene detection. In conclusion, the immunochromatographic strip that was established is rapid, sensitive, specific, simple, practical, and broad-spectrum; additionally, it has the potential to serve as an on-site rapid detection method of IBV and can facilitate the surveillance and control of the disease, especially in resource-limited areas.

Components from Curcuma longa (Turmeric) Against Hepatobiliary Diseases Based on Gut-Liver Axis: Pharmacotherapeutic Properties and Potential Clinical Applications.

Turmeric is widely used worldwide, and there are many examples of its use in treating hepatobiliary diseases. The gut-liver axis is a bidirectional relationship between gut microorganisms and the liver that is closely related to the pathogenesis of hepatobiliary diseases. This review systematically summarizes the components of turmeric. It links the studies on turmeric affecting gut microorganisms to its effects on liver and biliary diseases to explain the potential mechanism of turmeric's regulation of the gut-liver axis. Besides, ethnopharmacology, phytochemicals, and clinical adverse events associated with turmeric have been researched. Furthermore, turmeric is a safe agent with good clinical efficacy and without apparent toxicity at a certain amount. By summarizing the influence of turmeric on the liver by regulating the gut-liver axis, especially the gut microbiota, it provides a preclinical basis for using turmeric as a safe and effective therapeutic agent for the prevention and treatment of hepatobiliary diseases based on the gut-liver axis. However, more efforts should be made to exploit its clinical application further.

Modulating Effects of Turmeric Polysaccharides on Immune Response and Gut Microbiota in Cyclophosphamide-Treated Mice.

Turmeric, a traditional medicinal herb, is commonly used as a dietary and functional ingredient. This study aimed to investigate the effect of turmeric polysaccharides (TPs) on intestinal immunity and gut microbiota in cyclophosphamide (Cy)-induced immunosuppressed BALB/c mice. We verified that the oral administration of TPs-0 and TPs-3 (200 and 400 mg/kg, bw) improved thymus and spleen indexes, increased the whole blood immune cells (WBC) and lymph count index, and stimulated the secretion of serum immunoglobulin IgG. More importantly, TPs-0 and TPs-3 could repair intestinal immune damage and reduce intestinal inflammation. The specific mechanism is ameliorating the intestinal pathological damage, promoting CD4+ T cell secretion, regulating the expression of related cytokines, and reducing the level of critical proteins in the NF-κB/iNOS pathway. Interestingly, the intake of TPs-0 and TPs-3 significantly increased the content of short-chain fatty acids (SCFAs). Moreover, TPs-0 and TPs-3 relieved the intestinal microbiota disorder via the proliferation of the abundance of Lactobacillus and Bacteroides and the inhibition of Staphylococcus. Cumulatively, our study suggests that TPs-0 and TPs-3 can relieve intestinal immune damage by repairing the immune barrier and regulating intestinal flora disorders. TPs have potential applications for enhancing immunity as a functional food.

Tannic acid and zinc ion coordination of nanase for the treatment of inflammatory bowel disease by promoting mucosal repair and removing reactive oxygen and nitrogen species.

Colon mucosal overexpression of reactive oxygen and nitrogen species (RONS) accelerates the development of inflammatory bowel disease (IBD) and destroys the mucosa and its barrier. IBD can be alleviated by removing RONS from the inflamed colon. The preparation of strong and efficient nanoantioxidants remains a challenge despite the development of numerous nanoantioxidants. In this paper, Zn-TA nanoparticles with fine hollow microstructure (HZn-TA) were successfully prepared and could be effectively used to treat IBD. In the first step, ZIF-8 nanoparticles were synthesized by a one-pot method. On this basis, HZn-TA nanoparticles were etched by TA, and a multifunctional nanase was developed for the treatment of IBD. RONS, including reactive oxygen species (ROS) and nitric oxide (NO), can be eliminated to increase cell survival following Hydrogen peroxide (H2O2) stimulation, including reactive oxygen species (ROS) and nitric oxide (NO with hydrogen peroxide (H2O2). In a model for preventing and delaying acute colitis, clearance of RONS has been shown to reduce intestinal inflammation in mice by reducing colon damage, proinflammatory cytokine levels, the spleen index, and body weight. Intestinal mucosal healing can be promoted by HZn-TA nanoparticles, which can upregulate zonula occludens protein 1 (ZO-1) and claudin-1 expression. Based on the results of this study, HZn-TA nanoparticles were able to effectively treat IBD with minimal adverse effects by being biocompatible, multienzyme active, and capable of scavenging RONS. Therefore, we pioneered the application of HZn-TA nanoparticles for the treatment of IBD, which are capable of clearing RONS without significant adverse effects. STATEMENT OF SIGNIFICANCE: ➢ HZn-TA nanoparticles were successfully prepared and could be effectively used to treat IBD. ➢ Intestinal mucosal healing can be promoted by HZn-TA nanoparticles, which can upregulate ZO-1 and claudin-1 expression. ➢ HZn-TA nanoparticles were able to effectively treat IBD with minimal adverse effects by being biocompatible, multienzyme active, and capable of scavenging RONS.

The progression of inorganic nanoparticles and natural products for inflammatory bowel disease.

There is a growing body of evidence indicating a close association between inflammatory bowel disease (IBD) and disrupted intestinal homeostasis. Excessive production of reactive oxygen species (ROS) and reactive nitrogen species (RNS), along with an increase in M1 proinflammatory macrophage infiltration during the activation of intestinal inflammation, plays a pivotal role in disrupting intestinal homeostasis in IBD. The overabundance of ROS/RNS can cause intestinal tissue damage and the disruption of crucial gut proteins, which ultimately compromises the integrity of the intestinal barrier. The proliferation of M1 macrophages contributes to an exaggerated immune response, further compromising the intestinal immune barrier. Currently, intestinal nanomaterials have gained widespread attention in the context of IBD due to their notable characteristics, including the ability to specifically target regions of interest, clear excess ROS/RNS, and mimic biological enzymes. In this review, we initially elucidated the gut microenvironment in IBD. Subsequently, we delineate therapeutic strategies involving two distinct types of nanomedicine, namely inorganic nanoparticles and natural product nanomaterials. Finally, we present a comprehensive overview of the promising prospects associated with the application of nanomedicine in future clinical settings for the treatment of IBD (graphic abstract). Different classes of nanomedicine are used to treat IBD. This review primarily elucidates the current etiology of inflammatory bowel disease and explores two prominent nanomaterial-based therapeutic approaches. First, it aims to eliminate excessive reactive oxygen species and reactive nitrogen species. Second, they focus on modulating the polarization of inflammatory macrophages and reducing the proportion of pro-inflammatory macrophages. Additionally, this article delves into the treatment of inflammatory bowel disease using inorganic metal nanomaterials and natural product nanomaterials.

Debittering of Emblica (Phyllanthus emblica L.) fruit powder: Preparation and biological activity.

Emblica, also known as Phyllanthus emblica L., is a drug homologous food that is rich in polyphenols with various biological activities. However, its bitterness and astringency pose a significant challenge to its utilization in food products. In this study, we aimed to identify the optimal conditions for debittering Emblica. Our findings revealed that the best debittering conditions were: temperature = 50 °C, pH = 4, α-l-rhamnosidase concentration 200 U/g, and time = 5 h. High-performance liquid chromatography (HPLC) and molecular docking analysis revealed that enzymatic hydrolysis partially removed bitterness compounds. The results of antioxidant activity, xanthine oxidase, and α-glucosidase inhibitory activity assays confirmed that the Emblica fruit powder still exhibited good biological activity after enzymatic debitterization. Moreover, gastric fluids treatment might contribute to the above enhancing effect of enzymatic hydrolysates of Emblica. This study provided a theoretical basis for promoting the processing and utilization of Emblica fruit powder, as well as understanding its biological activity.

Expert consensus on digital intraoral scanning technology / 口腔疾病防治

@#Digital intraoral scanning is a hot topic in the field of oral digital technology. In recent years, digital intraoral scanning has gradually become the mainstream technology in orthodontics, prosthodontics, and implant dentistry. The precision of digital intraoral scanning and the accuracy and stitching of data collection are the keys to the success of the impression. However, the operators are less familiar with the intraoral scanning characteristics, imaging processing, operator scanning method, oral tissue specificity of the scanned object, and restoration design. Thus far, no unified standard and consensus on digital intraoral scanning technology has been achieved at home or abroad. To deal with the problems encountered in oral scanning and improve the quality of digital scanning, we collected common expert opinions and sought to expound the causes of scanning errors and countermeasures by summarizing the existing evidence. We also describe the scanning strategies under different oral impression requirements. The expert consensus is that due to various factors affecting the accuracy of digital intraoral scanning and the reproducibility of scanned images, adopting the correct scanning trajectory can shorten clinical operation time and improve scanning accuracy. The scanning trajectories mainly include the E-shaped, segmented, and S-shaped methods. When performing fixed denture restoration, it is recommended to first scan the abutment and adjacent teeth. When performing fixed denture restoration, it is recommended to scan the abutment and adjacent teeth first. Then the cavity in the abutment area is excavated. Lastly, the cavity gap was scanned after completing the abutment preparation. This method not only meets clinical needs but also achieves the most reliable accuracy. When performing full denture restoration in edentulous jaws, setting markers on the mucosal tissue at the bottom of the alveolar ridge, simultaneously capturing images of the vestibular area, using different types of scanning paths such as Z-shaped, S-shaped, buccal-palatal and palatal-buccal pathways, segmented scanning of dental arches, and other strategies can reduce scanning errors and improve image stitching and overlap. For implant restoration, when a single crown restoration is supported by implants and a small span upper structure restoration, it is recommended to first pre-scan the required dental arch. Then the cavity in the abutment area is excavated. Lastly, scanning the cavity gap after installing the implant scanning rod. When repairing a bone level implant crown, an improved indirect scanning method can be used. The scanning process includes three steps: First, the temporary restoration, adjacent teeth, and gingival tissue in the mouth are scanned; second, the entire dental arch is scanned after installing a standard scanning rod on the implant; and third, the temporary restoration outside the mouth is scanned to obtain the three-dimensional shape of the gingival contour of the implant neck, thereby increasing the stability of soft tissue scanning around the implant and improving scanning restoration. For dental implant fixed bridge repair with missing teeth, the mobility of the mucosa increases the difficulty of scanning, making it difficult for scanners to distinguish scanning rods of the same shape and size, which can easily cause image stacking errors. Higher accuracy of digital implant impressions can be achieved by changing the geometric shape of the scanning rods to change the optical curvature radius. The consensus confirms that as the range of scanned dental arches and the number of data concatenations increases, the scanning accuracy decreases accordingly, especially when performing full mouth implant restoration impressions. The difficulty of image stitching processing can easily be increased by the presence of unstable and uneven mucosal morphology inside the mouth and the lack of relatively obvious and fixed reference objects, which results in insufficient accuracy. When designing restorations of this type, it is advisable to carefully choose digital intraoral scanning methods to obtain model data. It is not recommended to use digital impressions when there are more than five missing teeth.

Herb pairs containing Curcumae Rhizoma (Ezhu): A review of bio-active constituents, compatibility effects and t-copula function analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: An herbal pair is a classic form of clinical dispensing in Traditional Chinese Medicine (TCM), often used in prescriptions to enhance the effect or reduce potential side effects. It is the smallest component unit of Chinese medicine prescription and an essential bridge between Chinese medicine and prescription. Curcumae Rhizoma (called Ezhu in Chinese) is a representative TCM herb that promotes blood circulation and removes blood stasis. It has been used in Chinese medicine for thousands of years. Ezhu is generally used in clinical applications as a part of a "drug pair" to treat heartburn, stomach pain, tumour, amenorrhea and abdominal pain caused by blood stasis, qi stagnation and injury. AIMS OF THE REVIEW: This review aims to summarize the latest and comprehensive situation of the biological activity and clinical application of drug pairs containing Ezhu, find the law of Ezhu compatibility application, and discuss the rationalization of Ezhu drug compatibility. For Ezhu, herb pairs to provide a theoretical basis for clinical research in TCM and serve as a research foundation for developing new drugs. MATERIALS AND METHODS: Using a self-built prescription database and Apriori algorithm for association rule mining. A systematic search for studies on herb pairs containing Ezhu was carried out by using the internet databases of PubMed, CNKI, Baidu Scholar, Google Scholar and Web of Science, as well as other relevant textbooks, reviews and documents (e.g. Chinese Pharmacopoeia, 2020 edition, Chinese herbal classic books and PhD and MSc theses, etc.). Among them with keywords including "Curcumae Rhizoma", "Ezhu", "herb pairs", "clinical application", etc. and their combinations. Moreover, the t-copula function was used to analyse the dose-coupling effect of five drug pairs, including Ezhu. RESULTS: The preliminary statistical analysis retrieved Ezhu prescriptions from self-built prescription database and internet databases. The results showed that the compatibility frequency of Ezhu with the other five Chinese medicines was high. Most of these selected herbal combinations are used to treat internal diseases. In this paper, the progress of the ethnopharmacology of Ezhu was reviewed, emphasizing the changes in bioactive components and compatibility of Chinese traditional medicine combinations such as Ezhu and Astragalus Curcuma (Sparganium stoloniferum Buch. -Ham; called Sanleng in Chinese), Ezhu and Astragali Radix (Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao, Astragalus membranaceus (Fisch.) Bge.; called Huangqi in Chinese). Some other varieties, such as Ezhu and Rhizoma Chuanxiong (Ligusticum chuanxiong Hort.; called Chuanxiong in Chinese), Trionycis Carapax (Trionyx sinensis Wiegmann; called Biejia in Chinese), and Coptidis Rhizoma (Coptis chinensis Franch., Coptis deltoidea C. Y. Cheng et Hsiao, Coptis teeta Wall.; called Huanglian in Chinese), are also recorded in ancient books but rarely researched. The dose of Ezhu is strongly correlated with the amount of Sanleng, Huangqi, Biejia, Chuanxiong and Huanglian, respectively. Furthermore, there was a positive correlation between them. CONCLUSIONS: The bioactive components and compatibility effects of Ezhu herb pairs were studied in detail using data mining and t-copula function analysis. Ezhu and Astragalus Curcuma (Sanleng) mainly treat gynecological disorders by activating blood circulation and relieving congestion. Ezhu and Astragali Radix (Huangqi) drug pair and Ezhu and Trionycis Carapax (Biejia) drug pair are all commonly used in the clinical treatment of tumors, the former is mainly used clinically for the treatment of digestive tract-related inflammation and tumors, liver cancer and gynecological tumors, and the latter is commonly used for the treatment of malignant tumors, such as liver cancer and mammary cancer.

Kiwifruit Monodehydroascorbate Reductase 3 Gene Negatively Regulates the Accumulation of Ascorbic Acid in Fruit of Transgenic Tomato Plants.

Ascorbic acid is a potent antioxidant and a crucial nutrient for plants and animals. The accumulation of ascorbic acid in plants is controlled by its biosynthesis, recycling, and degradation. Monodehydroascorbate reductase is deeply involved in the ascorbic acid cycle; however, the mechanism of monodehydroascorbate reductase genes in regulating kiwifruit ascorbic acid accumulation remains unclear. Here, we identified seven monodehydroascorbate reductase genes in the genome of kiwifruit (Actinidia eriantha) and they were designated as AeMDHAR1 to AeMDHAR7, following their genome identifiers. We found that the relative expression level of AeMDHAR3 in fruit continued to decline during development. The over-expression of kiwifruit AeMDHAR3 in tomato plants improved monodehydroascorbate reductase activity, and, unexpectedly, ascorbic acid content decreased significantly in the fruit of the transgenic tomato lines. Ascorbate peroxidase activity also increased significantly in the transgenic lines. In addition, a total of 1781 differentially expressed genes were identified via transcriptomic analysis. Three kinds of ontologies were identified, and 106 KEGG pathways were significantly enriched for these differently expressed genes. Expression verification via quantitative real-time PCR analysis confirmed the reliability of the RNA-seq data. Furthermore, APX3, belonging to the ascorbate and aldarate metabolism pathway, was identified as a key candidate gene that may be primarily responsible for the decrease in ascorbic acid concentration in transgenic tomato fruits. The present study provides novel evidence to support the feedback regulation of ascorbic acid accumulation in the fruit of kiwifruit.

Melatonin Relieves Paclitaxel-Induced Neuropathic Pain by Regulating pNEK2-Dependent Epigenetic Pathways in DRG Neurons.

The neurohormone melatonin (MLT) demonstrates promising potential in ameliorating neuropathic pain induced by paclitaxel (PTX) chemotherapy. However, little is known about its protective effect on dorsal root ganglion (DRG) neurons in neuropathic pain resulting from the chemotherapeutic drug PTX. Here, PTX-treated rats revealed that intrathecal administration of MLT dose-dependently elevated hind paw withdrawal thresholds and latency, indicating that MLT significantly reversed PTX-induced neuropathic pain. Mechanistically, the analgesic effects of MLT were found to be mediated via melatonin receptor 2 (MT2), as pretreatment with an MT2 receptor antagonist inhibited these effects. Moreover, intrathecal MLT injection reversed the pNEK2-dependent epigenetic program induced by PTX. All of the effects caused by MLT were blocked by pretreatment with an MT2 receptor-selective antagonist, 4P-PDOT. Remarkably, multiple MLT administered during PTX treatment (PTX+MLTs) exhibited not only rapid but also lasting reversal of allodynia/hyperalgesia compared to single-bolus MLT administered after PTX treatment (PTX+MLT). In addition, PTX+MLTs exhibited greater efficacy in reversing PTX-induced alterations in pRSK2, pNEK2, JMJD3, H3K27me3, and TRPV1 expression and interaction in DRG neurons than PTX+MLT. These results indicated that MLT administered during PTX treatment reduced the incidence and/or severity of neuropathy and had a better inhibitory effect on the pNEK2-dependent epigenetic program compared to MLT administered after PTX treatment. In conclusion, MLT/MT2 is a promising therapy for the treatment of pNEK2-dependent painful neuropathy resulting from PTX treatment. MLT administered during PTX chemotherapy may be more effective in the prevention or reduction of PTX-induced neuropathy and maintaining quality.

Paeoniflorin, ferulic acid, and atractylenolide III improved LPS-induced neuroinflammation of BV2 microglia cells by enhancing autophagy.

Microglia hyperactivation is an important cause of neuroinflammation in Alzheimer's disease (AD). Paeoniflorin (PF), ferulic acid (FA), and atractylenolide III (ATL) are potent in anti-inflammation and neuroprotection. Multiple components can act on different targets simultaneously to exert synergistic therapeutic effects and exploring the synergistic potential between compounds is an important area of research. We investigated the effects of PF, FA, and ATL, alone or in combination, on LPS-induced neuroinflammation and autophagy in BV2 microglia cells. We found that PF, FA, and ATL, alone or in combination, significantly reduced the production of inflammatory factors such as IL-6, IL-1ß, and TNF-α, especially in the PF + FA + ATL group, which performed the best. In addition, the combination of PF, FA, and ATL significantly increased the expression of autophagy-related proteins p-AMPK, p-ULK1, Beclin1, LC3, and TFEB and decreased the expression of p62. Moreover, the restoration of autophagic flux by the combination of PF, FA, and ATL was abrogated by the addition of the autophagy inhibitor Wortmannin. In conclusion, PF, FA, and ATL have a synergistic effect in reducing LPS-induced inflammatory factor release from BV2 microglia cells, and its protective effect may be through activation of the AMPK/ULK1/TFEB autophagic signaling pathway.

Protective Effect of Ferulic Acid on Lipopolysaccharide-Induced BV2 Microglia Inflammation via AMPK/mTOR Signaling Pathway.

In neurodegenerative diseases, microglial activation and neuroinflammation are essential for the control and progression of neurodegenerative diseases. Mitigating microglium-induced inflammation is one strategy for hindering the progression of neurodegenerative diseases. Ferulic acid (FA) is an effective anti-inflammatory agent, but its potential role and regulation mechanism in neuroinflammatory reactions have not been fully studied. In this study, the neuroinflammation model was established by lipopolysaccharide (LPS), and the inhibitory effect of FA on neuroinflammation of BV2 microglia was studied. The results showed that FA significantly reduced the production and expression of reactive oxygen species (ROS), tumor necrosis factor-α (TNF-α), leukocyte-6 (IL-6) and interleukin-1ß (IL-1ß). We further studied the mechanism of FA's regulation of LPS-induced BV2 neuroinflammation and found that FA can significantly reduce the expression of mTOR in BV2 microglia induced by LPS, and significantly increase the expression of AMPK, indicating that FA may have an anti-inflammatory effect by activating the AMPK/mTOR signaling pathway to regulate the release of inflammatory mediators (such as NLRP3, caspase-1 p20 and IL-1ß). We further added an autophagy inhibitor (3-MA) and an AMPK inhibitor (compound C, CC) for reverse verification. The results showed that FA's inhibitory effects on TNF-α, IL-6 and IL-1ß and its regulatory effect on AMPK/mTOR were destroyed by 3-MA and CC, which further indicated that FA's inhibitory effect on neuroinflammation is related to its activation of the AMPK/mTOR autophagy signaling pathway. In a word, our experimental results show that FA can inhibit LPS-induced neuroinflammation of BV2 microglia by activating the AMPK/mTOR signaling pathway, and FA may be a potential drug for treating neuroinflammatory diseases.

Phosphate NIMA-Related Kinase 2-Dependent Epigenetic Pathways in Dorsal Root Ganglion Neurons Mediates Paclitaxel-Induced Neuropathic Pain.

BACKGROUND: The microtubule-stabilizing drug paclitaxel (PTX) is an important chemotherapeutic agent for cancer treatment and causes peripheral neuropathy as a common side effect that substantially impacts the functional status and quality of life of patients. The mechanistic role for NIMA-related kinase 2 (NEK2) in the progression of PTX-induced neuropathic pain has not been established. METHODS: Adult male Sprague-Dawley rats intraperitoneally received PTX to induce neuropathic pain. The protein expression levels in the dorsal root ganglion (DRG) of animals were measured by biochemical analyses. Nociceptive behaviors were evaluated by von Frey tests and hot plate tests. RESULTS: PTX increased phosphorylation of the important microtubule dynamics regulator NEK2 in DRG neurons and induced profound neuropathic allodynia. PTX-activated phosphorylated NEK2 (pNEK2) increased jumonji domain-containing 3 (JMJD3) protein, a histone demethylase protein, to specifically catalyze the demethylation of the repressive histone mark H3 lysine 27 trimethylation (H3K27me3) at the Trpv1 gene, thereby enhancing transient receptor potential vanilloid subtype-1 (TRPV1) expression in DRG neurons. Moreover, the pNEK2-dependent PTX response program is regulated by enhancing p90 ribosomal S6 kinase 2 (RSK2) phosphorylation. Conversely, intrathecal injections of kaempferol (a selective RSK2 activation antagonist), NCL 00017509 (a selective NEK2 inhibitor), NEK2-targeted siRNA, GSK-J4 (a selective JMJD3 inhibitor), or capsazepine (an antagonist of TRPV1 receptor) into PTX-treated rats reversed neuropathic allodynia and restored silencing of the Trpv1 gene, suggesting the hierarchy and interaction among phosphorylated RSK2 (pRSK2), pNEK2, JMJD3, H3K27me3, and TRPV1 in the DRG neurons in PTX-induced neuropathic pain. CONCLUSIONS: pRSK2/JMJD3/H3K27me3/TRPV1 signaling in the DRG neurons plays as a key regulator for PTX therapeutic approaches.

Curcumae rhizoma and its major constituents against hepatobiliary disease: Pharmacotherapeutic properties and potential clinical applications.

BACKGROUND: Hepatobiliary disease currently serves as an urgent health issue in public due to health-modulating factors such as extension of life expectancy, increasingly sedentary lifestyles and over-nutrition. A definite treatment remains lacking owing to different stages of the disease itself and its intricate pathogenesis. Traditional Chinese medicine (TCM) has been gradually popularized in clinic with the satisfactory efficacy and good safety. Curcumae Rhizoma (called E Zhu, EZ in Chinese) is a representative herb, which has been used to treat hepatobiliary disease for thousands of years. PURPOSE: To systematically summarize the recent research advances on the pharmacological activities of EZ and its constituents, explain the underlying mechanisms of preventing and treating hepatobiliary diseases, and assess the shortcomings of existing work. Besides, ethnopharmacology, phytochemicals, and toxicology of EZ have been researched. METHODS: The information about EZ was collected from various sources including classic books about Chinese herbal medicine, and scientific databases including Web of Science, PubMed, ScienceDirect, Springer, ACS, SCOPUS, CNKI, CSTJ, and WANFANG using keywords given below and terms like pharmacological and phytochemical details of this plant. RESULTS: The chemical constituents isolated and identified from EZ, such as terpenoids including ß-elemene, furanodiene, germacrone, etc. and curcuminoids including curcumin, demethoxycurcumin, bisdemethoxycurcumin, etc. prove to have hepatoprotective effect, anti-liver fibrotic effect, anti-fatty liver effect, anti-liver neoplastic effect, and cholagogic effect through TGF-ß1/Smad, JNK1/2-ROS, NF-κB and other anti-inflammatory and antioxidant signaling pathways. Also, EZ is often combined with other Chinese herbs in the treatment of hepatobiliary diseases with good clinical efficacy and no obvious adverse reactions. CONCLUSION: It provides a preclinical basis for the efficacy of EZ as an effective therapeutic agent for the prevention and treatment of hepatobiliary diseases. Even so, the further studies still needed to alleviate hepatotoxicity and expand clinical application.

Public knowledge and attitudes toward automated external defibrillators use among first aid eLearning course participants: a survey.

OBJECTIVE: Survival from out-of-hospital cardiac arrest (OHCA) often depends on the effective and immediate use of automated external defibrillators (AEDs). Given that there have been few studies about AED use in China, the purpose of this study is to investigate the knowledge and attitudes regarding AED use among the Chinese public, then provide an effective suggestion for AED education strategies and legislation. METHOD: The online survey was conducted among Chinese participants of the First Aid eLearning courses in June 2020. RESULT: A total of 2565 (95.00%) surveys were completed, only 23.46% of respondents with non-medical related respondents reported having attended previous AED training courses. Regarding the basic knowledge of AEDs, few respondents (12.28%, n = 315) could answer all four questions correctly. 95.67% (n = 2454) were willing to learn AED use. Even if without the precondition of being skilled in AEDs, the female was more likely to rescue OHCA patients than the male (p = 0.003). Almost all respondents (96.65%) showed a strong willingness to rescue OHCA patients with training in using AEDs. The top four barriers to rescuing OHCA patients were lack of practical performing ability (60.47%), fear of hurting patients (59.30%), inadequate knowledge of resuscitation techniques (44.19%), and worry about taking legal responsibility (26.74%). CONCLUSION: Our study reflects a deficiency of AED knowledge among the general public in China. However, positive attitudes towards rescuing OHCA patients and learning AED use were observed, which indicates that measures need to be taken to disseminate knowledge and use of AEDs.

PO(CH2CH2CF3)3: an organic ultraviolet nonlinear optical material without any anionic group.

Researchers have focused on inorganic compounds to design deep ultraviolet (UV) nonlinear optical (NLO) materials according to anionic group theory, such as CO3 2-, NO3 -, SO4 2- and PO4 3- anions. Here we provide a new route to design an UV NLO material using a pure organic compound without any anions. Compound PO(CH2CH2CF3)31, an UV NLO material, has light transmittance up to 83% in the UV spectral region which is larger than most inorganic UV NLO materials. It also displays a wide transparent band, a SHG response of 0.30 × KH2PO4, and a cut-off edge below 200 nm. It displays ladder-like nonlinear optical properties weakened by 1.4 times at around T c, making compound 1 a potential temperature-controlled UV NLO material. Theoretical analyses reveal that the nonlinear optical properties are primarily due to O-2p, P-2p and F-2p.

Phylogenetic and Spatiotemporal Analyses of the Complete Genome Sequences of Avian Coronavirus Infectious Bronchitis Virus in China During 1985-2020: Revealing Coexistence of Multiple Transmission Chains and the Origin of LX4-Type Virus.

Infectious bronchitis (IB) virus (IBV) causes considerable economic losses to poultry production. The data on transmission dynamics of IBV in China are limited. The complete genome sequences of 212 IBV isolates in China during 1985-2020 were analyzed as well as the characteristics of the phylogenetic tree, recombination events, dN/dS ratios, temporal dynamics, and phylogeographic relationships. The LX4 type (GI-19) was found to have the highest dN/dS ratios and has been the most dominant genotype since 1999, and the Taiwan-I type (GI-7) and New type (GVI-1) showed an increasing trend. A total of 59 recombinants were identified, multiple recombination events between the field and vaccine strains were found in 24 isolates, and the 4/91-type (GI-13) isolates were found to be more prone to being involved in the recombination. Bayesian phylogeographic analyses indicated that the Chinese IBVs originated from Liaoning province in the early 1900s. The LX4-type viruses were traced back to Liaoning province in the late 1950s and had multiple transmission routes in China and two major transmission routes in the world. Viral phylogeography identified three spread regions for IBVs (including LX4 type) in China: Northeastern China (Heilongjiang, Liaoning, and Jilin), north and central China (Beijing, Hebei, Shanxi, Shandong, and Jiangsu), and Southern China (Guangxi and Guangdong). Shandong has been the epidemiological center of IBVs (including LX4 type) in China. Overall, our study highlighted the reasons why the LX4-type viruses had become the dominant genotype and its origin and transmission routes, providing more targeted strategies for the prevention and control of IB in China.