A novel deep eutectic solvent modified magnetic covalent organic framework for the selective separation and determination of trace copper ion in medicinal plants and environmental samples.

BACKGROUND: Pretreatment techniques should be introduced before metal ion determination because there is very low content of heavy metals in Chinese medicinal plants and environmental samples. Magnetic dispersive micro solid phase extraction (MDMSPE) has been widely used for the separation and adsorption of heavy metal pollutants in medicinal plants and environmental samples. However, the majority of MDMSPE adsorbents have certain drawbacks, including low selectivity, poor anti-interference ability, and small adsorption capacity. Therefore, modifying currently available adsorption materials has gained attention in research. RESULTS: In this study, a novel adsorbent MCOF-DES based on a magnetic covalent organic framework (MCOF) modified by a new deep eutectic solvent (DES) was synthesized for the first time and used as an adsorbent of MDMSPE. The MDMSPE was combined with inductively coupled plasma optical emission spectrometry (ICP-OES) for selective separation, enrichment, and accurate determination of trace copper ion (Cu2+) in medicinal plants and environmental samples. Various characterization results show the successful preparation of new MCOF-DES. Under the optimal conditions, the enrichment factor (EF) of Cu2+ was 30, the limit of detection (LOD) was 0.16 µg L-1, and the limit of quantitation (LOQ) was 0.54 µg L-1. The results for the determination of Cu2+ were highly consistent with those of inductively coupled plasma mass spectrometry (ICP-MS), which verified the accuracy and reliability of the method. SIGNIFICANCE: The established method based on a new adsorption material MCOF-DES has achieved the selective separation and determination of trace Cu2+ in medicinal and edible homologous medicinal materials (Phyllanthus emblica Linn.) and environmental samples (soil and water), which provides a promising, selective, and sensitive approach for the determination of trace Cu2+ in other real samples.

Vitamin D binding protein (VDBP) hijacks twist1 to inhibit vasculogenic mimicry in hepatocellular carcinoma.

Rationale: Vitamin D (VD) has been suggested to have antitumor effects, however, research on the role of its transporter vitamin D-binding protein (VDBP, gene name as GC) in tumors is limited. In this study, we demonstrated the mechanism underlying the inhibition of vasculogenic mimicry (VM) by VDBP in hepatocellular carcinoma (HCC) and proposed an anti-tumor strategy of combining anti-PD-1 therapy with VD. Methods: Three-dimensional cell culture models and mice with hepatocyte-specific GC deletion were utilized to study the correlation between VDBP expression and VM. A patient-derived tumor xenograft (PDX) model was further applied to validate the therapeutic efficacy of VD in combination with an anti-PD-1 drug. Results: The study revealed that VDBP expression is negatively correlated with VM in HCC patients and elevated VDBP expression is associated with a favorable prognosis. The mechanism studies suggested VDBP hindered the binding of Twist1 on the promoter of VE-cadherin by interacting with its helix-loop-helix DNA binding domain, ultimately leading to the inhibition of VM. Furthermore, VD facilitated the translocation of the vitamin D receptor (VDR) into the nucleus where VDR interacts with Yin Yang 1 (YY1), leading to the transcriptional activation of VDBP. We further demonstrated that the combination of VD and anti-PD-1 led to an improvement in the anti-tumor efficacy of an anti-PD-1 drug. Conclusion: Collectively, we identified VDBP as an important prognostic biomarker in HCC patients and uncovered it as a therapeutic target for enhancing the efficacy of immune therapy.

Network pharmacology-based analysis of Jin-Si-Wei on the treatment of Alzheimer's disease.

ETHNOPHARMACOLOGICAL RELEVANCE: Jin-Si-Wei (JSW), a traditional Chinese medicine (TCM) formula, have cognitive enhancing effect and delay the memory decline in an animal model of AD， which has been reported. However, the therapeutic mechanism of JSW in the treatment of AD remains unclear. AIM OF THE STUDY: This study aimed to verify the pharmacodynamics of JSW in the treatment of AD, and to explore its potential mechanism based on network pharmacology, molecular docking and experimental validation both in vitro and in vivo. MATERIALS AND METHODS: In this study, the underlying mechanism of JSW against AD was investigated by the integration of network pharmacology. Then, the core pathways and biological process of JSW were verified by experiment, including behavioral test and pathological and biochemical assays with 6-month-old APPswe/PS1ΔE9 transgenic (APP/PS1) mice in vivo and verified with Aß1-42-stimulated SH-SY5Y cells in vitro. At last, molecular docking was used to show the binding activity of each active ingredient to the core genes of JSW treatment in AD. RESULTS: A Drug-Ingredient-Target network was established, which included 363 ingredients and 116 targets related to the JSW treatment of AD. The main metabolic pathway of JSW treatment for AD is neuroactive ligand-receptor interaction pathway, and biological processes are mainly involved in Aß metabolic process. In vivo experiments, compared with APP/PS1 mice, the cognitive and memory ability of mice was significantly improved after JSW administration. In brain tissue of APP/PS1 mice, JSW could increase the contents of low-density lipoprotein receptor-related protein 1 (LRP-1), enkephalinase (NEP) and Acetyl choline (ACh), and decrease the contents of Aß1-42, amyloid precursor protein (APP) and receptor for advanced glycation end products (RAGE), decrease the vitality of cholinesterase (AChE) and choline acetyltransferase (ChAT). Besides, JSW could increase α-secretase expression and decrease ß/γ-secretase expression, and improve the number and morphology of synapses in CA1 region of the hippocampus of APP/PS1 mice. In vitro experiments, Drug-Containing Serum (JSW-serum) has a neuroprotective effect by reducing the apoptosis on Aß1-42-stimulated SH-SY5Y cells. Molecular docking results showed that 2-Isopropyl-8-methylphenanthrene-3,4-dione had strong binding activity with PTGS2, which maybe a potential ingredient for the treatment of AD. CONCLUSIONS: JSW improves AD in APP/PS1 mice, and this therapeutic effect may be achieved in part by altering the neuroactive ligand-receptor interaction pathway.

Role of epigenetic modifications mediated by vitamins and trace elements in inflammatory bowel disease.

Graphical abstract [Formula: see text] Numerous environmental factors frequently emerge as primary determinants of inflammatory bowel disease (IBD). Diet is a major component of environmental factors, and the consumption of vitamins (A, B, C and D) and trace elements (calcium, iron, zinc and selenium) exerts an impact on the progression of IBD through epigenetic modifications. Intake of vitamins A, B, C and D, as well as excessive amounts of iron and calcium, can modulate the condition of IBD by regulating the levels of DNA methylation, histone acetylation and miRNA. Zinc and selenium alleviate the progression of IBD by regulating the levels of promoter methylation or histone ubiquitination, respectively. Graphical Abstract was adapted from 'Epigenetic levels (layout)', by BioRender.com. Retrieved from https://app.biorender.com/biorender-templates.

Oral Nanotherapeutics of Andrographolide/Carbon Monoxide Donor for Synergistically Anti-inflammatory and Pro-resolving Treatment of Ulcerative Colitis.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease of unknown etiology affecting the colon and rectum. Current therapeutics are focused on suppressing inflammation but are ineffective. Combining anti-inflammatory therapeutic approaches with pro-resolution might be a superior strategy for UC treatment. Andrographolide (AG), an active compound from the plant Andrographis paniculata, presented anti-inflammatory effects in various inflammatory diseases. Gaseous mediators, such as carbon monoxide (CO), have a role in inflammatory resolution. Herein, we developed a dextran-functionalized PLGA nanocarrier for efficient delivery of AG and a carbon monoxide donor (CORM-2) for synergistically anti-inflammatory/pro-resolving treatment of UC (AG/CORM-2@NP-Dex) based on PLGA with good biocompatibility, slow drug release, efficient targeting, and biodegradability. The resulting nanocarrier had a nano-scaled diameter of ∼200 nm and a spherical shape. After being coated with dextran (Dex), the resulting AG/CORM-2@NP-Dex could be efficiently internalized by Colon-26 and Raw 264.7 cells in vitro and preferentially localized to the inflamed colon with chitosan/alginate hydrogel protection by gavage. AG/CORM-2@NP-Dex performed anti-inflammatory effects by eliminating the over-production of pro-inflammatory mediator, nitric oxide (NO), and down-regulating the expression of pro-inflammatory cytokines (TNF-α, IL-1ß and IL-6), while it showed pro-resolving function by accelerating M1 to M2 macrophage conversion and up-regulating resolution-related genes (IL-10, TGF-ß, and HO-1). In the colitis model, oral administration of AG/CORM-2@NP-Dex in a chitosan/alginate hydrogel also showed synergistically anti-inflammatory/pro-resolving effects, therefore relieving UC effectively. Without appreciable systemic toxicity, this bifunctional nanocarrier represents a novel therapeutic approach for UC and is expected to achieve long-term inflammatory remission.

Genipin Attenuates Sepsis-Induced Splenocyte Apoptosis via the Inhibition of Endoplasmic Reticulum Stress.

Endoplasmic reticulum (ER) dysfunction is characterized by ER stress, which can be triggered by sepsis. Recent studies have reported that lessening ER stress is a promising therapeutic approach to improving the outcome of sepsis. Genipin is derived from gardenia fruit, which is a traditional Chinese medicinal herb for anti-inflammation. Here, mice were treated with genipin (2.5 mg/kg) intravenously to assess its biological effects and underlying mechanism against polymicrobial sepsis. Furthermore, the present study focused on detecting the levels of ER stress-related proteins, including protein kinase R-like ER kinase (PERK), glucose-regulated protein of 78 kDa (GRP78), phosphorylated-eukaryotic initiation factor 2α (p-eIF2α), and CCAAT/enhancer binding protein (C/EBP) homologous protein (CHOP). The results demonstrated that genipin significantly decreased the serum concentrations of tumor necrosis factor-α and interleukin-6, alleviated histopathological damage to the lungs, livers and spleens, and even improved the survival rates of septic mice. Moreover, sepsis significantly upregulated the protein expression levels of splenic GRP78, PERK, p-eIF2α and CHOP, but their levels were significantly suppressed by genipin. Furthermore, genipin also significantly downregulated cleaved caspase-3 expression levels and reduced sepsis-induced splenocyte apoptosis. In conclusion, genipin potentially improved the survival rate of sepsis and attenuated sepsis-induced organ injury and an excessive inflammatory response in mice. The effects of genipin against sepsis were potentially associated with decreased splenocyte apoptosis via the attenuation of sepsis-induced ER stress to further inhibit ER stress-induced apoptosis.

Fusidic Acid and Its Major Active Metabolite Penetration into Cerebrospinal Fluid for Assessing Treatment of Intracranial Infections.

Fusidic acid (FA) had excellent antimicrobial effects due to its unique mechanism of action. Since 1962, FA has been widely used in the systemic and topical treatment of staphylococcal infections and exhibits a well-characterized potency against methicillin-susceptible Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, and methicillin-resistant coagulase-negative Staphylococci. In view of the spectrum of activity, no cross-resistance with other clinically used antibiotics, and potential penetration into brain tissue, FA was used to treat possible gra-positive bacteria in 3 patients with intracranial infections in the present report. FA and its active metabolite (3-keto FA) were measured in plasma and cerebrospinal fluid (CSF) to assess the treatment of FA, and the results indicated that 1,500 mg per day of FA was sufficient to achieve therapeutic concentrations in both plasma and CSF in intracranial infection patients, while the dosage did not experience unexpected regimen-related toxicity.

Integrating network pharmacology, UPLC-Q-TOF-MS and molecular docking to investigate the effect and mechanism of Chuanxiong Renshen decoction against Alzheimer's disease.

BACKGROUND AND AIM: Chuanxiong Renshen decoction (CRD) is a traditional Chinese medicine compound used to treat Alzheimer's disease (AD). However, the effects and active ingredients of CRD and its mechanism have not been clarified. We aimed to determine the neuroprotective effects of CRD in a triple-transgenic mouse model of AD (3 × Tg-AD) and investigate the possible active ingredients and their mechanisms. METHODS: Morris water maze (MWM) tests were used to determine the protective effect of CRD on learning and memory ability. Afterward, we used brain tissue staining, immunofluorescent staining and western blotting to detect the neuroprotective effects of CRD. Ultraperformance liquid-chromatography-quadrupole-time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS) was applied to determine the ingredients of CRD, and the potential AD targets were obtained from DisGeNET and the GeneCards database. The protein‒protein interaction (PPI) network was built with the additional use of STRING 11.0. Metascape was used in the pathway enrichment analysis. Discovery Studio 2016 (DS) software was used to analyze the binding ability of CRD and AD-related genes. Finally, we verified the regulatory effect of CRD on the predicted core targets EGFR and CASP3 by western blotting. RESULTS: Our study indicated that CRD can significantly improve learning and memory, reduce the expression of Aß and protect neurons. A total of 95 ingredients were identified in the CRD. Then, 25 ingredients were identified in serum, and 5 ingredients were identified in the brain tissue homogenate. PPI network analysis identified CASP3, EGFR, APP, CNR1, HIF1A, PTGS2 and MTOR as hub targets. KEGG and GO analyses revealed that the TNF signaling pathway and MAPK signaling pathway were enriched in multiple targets. The results of molecular docking proved that the binding of the ingredients with potential key targets was excellent. The western blotting results showed that CRD could significantly reduce the expression of CASP3 and EGFR in the hippocampus of 3 × Tg-AD mice. Combined with literature analysis, we assumed the neuroprotective effect of CRD on AD may occur through regulation of the MAPK signaling pathway. CONCLUSION: CRD significantly alleviated injury in 3 × Tg-AD mice. The possible active ingredients are ferulic acid, rutin, ginsenoside Rg1 and panaxydol. The therapeutic effect of CRD on AD is achieved through the downregulation of CASP3 and EGFR. The neuroprotective effect of CRD on AD may occur through regulation of the MAPK signaling pathway.

Postoperative Chemoradiotherapy With Capecitabine and Oxaliplatin vs Capecitabine for Stage II to III Rectal Cancer: A Randomized Clinical Trial.

Importance: Several studies have explored the efficacy and toxic effects of concurrent 5-fluorouracil (5-FU)- or capecitabine-based chemoradiotherapy (CRT) with or without oxaliplatin in the neoadjuvant setting. Addition of oxaliplatin to 5-FU or capecitabine elicited similar outcomes but with significantly increased toxic effects; however, there is a need for randomized clinical trials comparing 2 CRT regimens for patients receiving CRT in the adjuvant setting. Objective: To explore the efficacy and toxic effects of oxaliplatin combined with postoperative concurrent capecitabine and radiotherapy (RT) for pathological stage II and III rectal cancer. Design, Setting, and Participants: This multicenter randomized clinical trial enrolled patients from 7 centers in China between April 1, 2008, and December 30, 2015. Patients with pathologically confirmed stage II and III rectal cancer were randomized (1:1) to receive concurrent CRT with capecitabine or capecitabine plus oxaliplatin. Analysis was conducted from December 31, 2019, to March 15, 2020. Interventions: RT comprised 45 to 50 Gy in 25 fractions of 1.8 to 2.0 Gy over 5 weeks. In the capecitabine with RT group, concurrent chemotherapy included 2 cycles of capecitabine (1600 mg/m2) on days 1 to 14 and 22 to 35. The capecitabine and oxaliplatin with RT group received identical postoperative RT to that in the capecitabine with RT group combined with capecitabine (1300 mg/m2) on days 1 to 14 and 22 to 35 and a 2-hour infusion of oxaliplatin (60 mg/m2) on weeks 1, 2, 4, and 5. Patients in both groups received adjuvant chemotherapy (capecitabine or fluorouracil and oxaliplatin) after CRT. Main Outcomes and Measures: The primary end point was 3-year disease-free survival (DFS). Results: A total of 589 patients (median [IQR] age, 55 [47-52] years; 375 [63.7%] men and 214 [36.3%] women) were enrolled, including 294 patients randomized to the capecitabine with RT group and 295 patients randomized to the capecitabine and oxaliplatin with RT group. Median (IQR) follow-up was 68 (45-96) months. Most patients had stage III disease (574 patients [75.9%]). Three-year DFS was 76.3% for the capecitabine with RT group and 74.1% for the capecitabine and oxaliplatin with RT group, and 5-year DFS was 72.0% for the capecitabine with RT group and 71.1% for the capecitabine and oxaliplatin with RT group (hazard ratio [HR], 1.07; 95% CI, 0.79-1.44; P = .68). There was no significant difference between groups in overall survival (HR, 0.93; 95% CI, 0.64-1.34; P = .70) or local recurrence (HR, 0.61; 95% CI, 0.31-1.22; P = .16). More grade 3 and 4 acute toxic effects were observed in the capecitabine and oxaliplatin with RT group than in the capecitabine with RT group (114 patients [38.6%] vs 84 patients [28.6%]; P = .01). Conclusions and Relevance: This randomized clinical trial found that addition of oxaliplatin to capecitabine-based postoperative CRT did not improve the efficacy of treatment but increased the risk of severe acute toxic effects. This finding highlights the basic role of postoperative capecitabine with RT for patients with locally advanced rectal cancer. Trial Registration: ClinicalTrials.gov Identifier: NCT00714077.

Corosolic acid and its structural analogs: A systematic review of their biological activities and underlying mechanism of action.

BACKGROUND: The corosolic acid (CA), also known as plant insulin, is a pentacyclic triterpenoid extracted from plants such as Lagerstroemia speciosa. It has been shown to have anti-diabetic, anti-inflammatory and anti-tumor effects. Its structural analogs ursolic acid (UA), oleanolic acid (OA), maslinic acid (MA), asiatic acid (AA) and betulinic acid (BA) display similar individual pharmacological activities to those of CA. However, there is no systematic review documenting pharmacological activities of CA and its structural analogues. This study aims to fill this gap in literature. PURPOSE: This systematic review aims to summarize the medical applications of CA and its analogues. METHODS: A systematic review summarizes and compares the extraction techniques, pharmacokinetic parameters, and pharmacological effects of CA and its structural analogs. Hypoglycemic effect is one of the key inclusion criteria for searching Web of Science, PubMed, Embase and Cochrane databases up to October 2020 without language restrictions. 'corosolic acid', 'ursolic acid', 'oleanolic acid', 'maslinic acid', 'asiatic acid', 'betulinic acid', 'extraction', 'pharmacokinetic', 'pharmacological' were used to extract relevant literature. The PRISMA guidelines were followed. RESULTS: At the end of the searching process, 140 articles were selected for the systematic review. Information of CA and five of its structural analogs including UA, OA, MA, AA and BA were included in this review. CA and its structural analogs are pentacyclic triterpenes extracted from plants and they have low solubilities in water due to their rigid scaffold and hydrophobic properties. The introduction of water-soluble groups such as sugar or amino groups could increase the solubility of CA and its structural analogs. Their biological activities and underlying mechanism of action are reviewed and compared. CONCLUSION: CA and its structural analogs UA, OA, MA, AA and BA are demonstrated to show activities in lowering blood sugar, anti-inflammation and anti-tumor. Their oral absorption and bioavailability can be improved through structural modification and formulation design. CA and its structural analogs are promising natural product-based lead compounds for further development and mechanistic studies.

Neurogenic dysphagia in traditional Chinese medicine.

BACKGROUND: Neurogenic dysphagia is the difficulty in swallowing caused by neurological diseases, which is a very common symptom in neurological disorders. In this paper, we try to summarize the opinions in the pathophysiology and therapy of dysphagia in ancient China (before AD 1840) through the records in the literatures from all the dynasties. METHODS: We searched the databases including Chinese Medical Classics, China National Knowledge Infrastructure, Wanfang Data, MEDLINE, and ISI Proceedings until July 2020, with the search terms "dysphagia" and "difficulty in swallowing" in English and their Chinese equivalents. RESULTS AND CONCLUSIONS: The concept of neurogenic dysphagia was first described as Hou Bi in the Yellow Emperor's Internal Classic, which is the first Chinese medical classic and the origin of traditional Chinese medicine (TCM) theory. In the different eras, the pathogenesis of neurogenic dysphagia was explained mainly by three theories in TCM, that is, the wind-phlegm blocking collaterals, the deficiency of liver and kidney-essence, and the Qi-stagnation with static blood. In addition to the TCM prescriptions, acupuncture is characteristic treatment and seems to be effective. However, the evidences of efficacy and safety from clinical trials are still required.

Differentiating Westlake Longjing tea from the first- and second-grade producing regions using ultra high performance liquid chromatography with quadrupole time-of-flight mass spectrometry-based untargeted metabolomics in combination with chemometrics.

There are numerous articles published for geographical discrimination of tea. However, few research works focused on the authentication and traceability of Westlake Longjing green tea from the first- and second-grade producing regions because the tea trees are planted in a limited growing zone with identical cultivate condition. In this work, a comprehensive analytical strategy was proposed by ultrahigh performance liquid chromatography-quadrupole time-of-flight mass spectrometry-based untargeted metabolomics coupled with chemometrics. The automatic untargeted data analysis strategy was introduced to screen metabolites that expressed significantly among different regions. Chromatographic features of metabolites can be automatically and efficiently extracted and registered. Meanwhile, those that were valuable for geographical origin discrimination were screened based on statistical analysis and contents in samples. Metabolite identification was performed based on high-resolution mass values and tandem mass spectra of screened peaks. Twenty metabolites were identified, based on which the two-way encoding partial least squares discrimination analysis was built for geographical origin prediction. Monte Caro simulation results indicated that prediction accuracy was up to 99%. Our strategy can be applicable for practical applications in the quality control of Westlake Longjing green tea.

San-Huang-Tang protects obesity/diabetes induced NAFLD by upregulating PGC-1α/PEPCK signaling in obese and galr1 knockout mice models.

ETHNOPHARMACOLOGICAL RELEVANCE: San-Huang-Tang (ST), a classic prescription, has been clinically used to cure diabetes and diabetes-associated metabolic disorders. Established studies have reported that ST can alleviate inflammation, obesity, hyperglycemia and insulin resistance. AIM OF THE STUDY: To the best of our knowledge, here, we reported for the first time the underlying mechanistic therapeutic efficacy of the ST against nonalcoholic fatty liver disease (NAFLD) in high-fat induced obese and galr1-deficient diabetic mice. MATERIALS AND METHODS: The obese and galr1-deficient mice were treated with ST at a dose of 10 g/kg every day for three weeks. Then food intake, body weight and insulin resistance indexes were measured. Western blotting, qRT-PCR, and plasma biochemical analyses were applied. RESULTS: ST reduced food intake, body weight, blood glucose level and insulin resistance, improved glucose tolerance in obese and galr1-deficient mice. Mechanistically, we confirmed that ST protected against NAFLD through activation of PGC-1α and its downstream signaling pathways as shown by the attenuated hepatic adipogenesis and lipid accumulation, increased hepatic fatty acid oxidation, regulated plasma lipid parameters, and increased energy expenditure and metabolic function in fat and muscle. CONCLUSIONS: Reduction in food intake produced by ST may contribute to the observed metabolic effects. Our findings strongly suggest that ST might be a potential novel therapeutic drug against obesity/diabetes-induced NAFLD and other metabolic disorders.

Involvement of Interleukin-10 in Analgesia of Electroacupuncture on Incision Pain.

OBJECTIVE: Postincision pain often occurs after surgery and is an emergency to be treated in clinic. Electroacupuncture (EA) is a Chinese traditional treatment widely used to cure acute or chronic pain, but its mechanism is not clear. Interleukin-10 (IL-10) is a powerful anti-inflammatory cytokine that shows neuroprotective effects in inflammation and injury in the CNS. The present study attempts to reveal that IL-10 is crucial for EA analgesia on postincision pain. METHODS: A model of incision pain was established in C57BL/6J mice. The pain threshold was detected by behavioral test, and the expression of IL-10 and its receptor was detected by an immunohistochemical method. C-fiber-evoked field potentials were recorded by in vivo analysis. RESULTS: The mechanical allodynia induced by paw incision was significantly inhibited by pretreatment of EA in mice. Intrathecal injection of IL-10 neutralizing antibody (2 µg/10 µL) but not intraplantar injection (10 µg/10 µL) reversed the analgesia of EA. The upregulations of IL-10 mRNA and protein were induced by EA at 6 h and 1 d after incision, respectively. Spinal long-term potentiation (LTP), a substrate for central sensitization, was also suppressed by EA with IL-10. IL-10 recombinant protein (1 µg/10 µL, i.t.) mimicked the analgesia of EA on mechanical allodynia and inhibition on the spinal LTP. Posttreatment of EA after incision also transitorily relieved the mechanical allodynia, which can be blocked by spinal IL-10 antibody. IL-10 and its receptor, IL-10RA, are predominantly expressed in the superficial spinal astrocytes. CONCLUSIONS: These results suggested that pretreatment of EA effectively prevented postincision pain and IL-10 in spinal astrocytes was critical for the analgesia of EA and central sensitization.

Berberine protects renal tubular cells against hypoxia/reoxygenation injury via the Sirt1/p53 pathway.

Berberine (BBR) has been demonstrated to protect against renal ischemia/reperfusion injury; however, the underlying molecular mechanism is largely unknown. In the present study, we examined the role of silent information regulator 1 (Sirt1)/p53 in the protective effect of BBR on hypoxia/reoxygenation (H/R)-mediated mitochondrial dysfunction in rat renal tubular epithelial cells (NRK-52E cells). NRK-52E cells were preconditioned with small interfering RNA targeting Sirt1 (Sirt1-siRNA) and BBR before subjected to H/R. Cell damage was assessed by CCK8 assay and detection of oxidative parameters. The apoptotic rate was determined by flow cytometry and Hoechst 33258 staining. The expression of apoptotic markers, Sirt1, p53 and the translocation of p53 were examined by Western blotting assay. Nuclear p53 deacetylation by Sirt1 was detected using immunoprecipitation. Compared with the H/R group, BBR pretreatment increased cell viability and inhibited mitochondrial oxidative stress and apoptosis. Protein expression of Sirt1 was also enhanced along with a reduction of p53. Furthermore, both nuclear translocation of p53 and its acetylation were inhibited in NRK-52E cells pretreated with BBR. However, the knockdown of Sirt1 counteracted the renoprotection of BBR. BBR preconditioning protects rat renal tubular epithelial cells against H/R-induced mitochondrial dysfunction via regulating the Sirt1/p53 pathway.

Astaxanthin improves cognitive performance in mice following mild traumatic brain injury.

BACKGROUND: Traumatic brain injury (TBI) produces lasting neurological deficits that plague patients and physicians. To date, there is no effective method to combat the source of this problem. Here, we utilized a mild, closed head TBI model to determine the modulatory effects of a natural dietary compound, astaxanthin (AST). AST is centrally active following oral administration and is neuroprotective in experimental brain ischemia/stroke and subarachnoid hemorrhage (SAH) models. We examined the effects of oral AST on the long-term neurological functional recovery and histological outcomes following moderate TBI in a mice model. METHODS: Male adult ICR mice were divided into 3 groups: (1) Sham+olive oil vehicle treated, (2) TBI+olive oil vehicle treated, and (3) TBI+AST. The olive oil vehicle or AST were administered via oral gavage at scheduled time points. Closed head brain injury was applied using M.A. Flierl weight-drop method. NSS, Rotarod, ORT, and Y-maze were performed to test the behavioral or neurological outcome. The brain sections from the mice were stained with H&E and cresyl-violet to test the injured lesion volume and neuronal loss. Western blot analysis was performed to investigate the mechanisms of neuronal cell survival and neurological function improvement. RESULTS: AST administration improved the sensorimotor performance on the Neurological Severity Score (NSS) and rotarod test and enhanced cognitive function recovery in the object recognition test (ORT) and Y-maze test. Moreover, AST treatment reduced the lesion size and neuronal loss in the cortex compared with the vehicle-treated TBI group. AST also restored the levels of brain-derived neurotropic factor (BDNF), growth-associated protein-43 (GAP-43), synapsin, and synaptophysin (SYP) in the cerebral cortex, which indicates the promotion of neuronal survival and plasticity. CONCLUSION: To the best of our knowledge, this is the first study to demonstrate the protective role and the underlining mechanism of AST in TBI. Based on these neuroprotective actions and considering its longstanding clinical use, AST should be considered for the clinical treatment of TBI.

Rapid Detection of Medicine Based on New Dielectric Barrier Discharge Ionization Mass Spectrometry / 分析化学

Currently, rapid detection of effective components in synthetic drugs and herbal medicine remains an important and difficult issue of medicine research. A novel ionization technique, called dielectric barrier discharge ionization ( DBDI ) , has strong ionization ability, and is suitable for weak polar substances. Besides, this technique possesses many intrinsic advantages, such as simplicity, rapidity, no complicated sample pretreatment, etc. In this study, a new DBDI ion source, based on single electrode technique, was used to detect four weak polar synthetic drugs. The results showed that the protonated molecular ions [ M+H]+of four weak polar synthetic drugs were observed obviously. What′s more, the DBDI ion source was also used for the rapid analysis of Radix Aconiti and Radix Aconiti Preparata pieces without any sample pretreatment. The result showed that the protonated molecular ions [M+H]+ and fragment ions [M+H-60]+of aconitine, hypaconitine, and mesaconitine were detected in Radix Aconiti. And only the fragment ions [M+H-60]+were detected in Radix Aconiti Preparat. The researches indicated that diester aconitine and monoester aconitine were the main effective components of Radix Aconiti Radix and Aconiti Preparat, respectively. The new DBDI ion source provided a fast and reliable method to identify effective components of medicine, showing a broad application prospects in synthetic drugs and herbal medicine research.

Rapid Detection of Medicine Based on New Dielectric Barrier Discharge Ionization Mass Spectrometry / 分析化学

Currently, rapid detection of effective components in synthetic drugs and herbal medicine remains an important and difficult issue of medicine research. A novel ionization technique, called dielectric barrier discharge ionization ( DBDI ) , has strong ionization ability, and is suitable for weak polar substances. Besides, this technique possesses many intrinsic advantages, such as simplicity, rapidity, no complicated sample pretreatment, etc. In this study, a new DBDI ion source, based on single electrode technique, was used to detect four weak polar synthetic drugs. The results showed that the protonated molecular ions [ M+H]+of four weak polar synthetic drugs were observed obviously. What′s more, the DBDI ion source was also used for the rapid analysis of Radix Aconiti and Radix Aconiti Preparata pieces without any sample pretreatment. The result showed that the protonated molecular ions [M+H]+ and fragment ions [M+H-60]+of aconitine, hypaconitine, and mesaconitine were detected in Radix Aconiti. And only the fragment ions [M+H-60]+were detected in Radix Aconiti Preparat. The researches indicated that diester aconitine and monoester aconitine were the main effective components of Radix Aconiti Radix and Aconiti Preparat, respectively. The new DBDI ion source provided a fast and reliable method to identify effective components of medicine, showing a broad application prospects in synthetic drugs and herbal medicine research.

Analgesic effects of Chinese Tuina massage in a rat model of pain.

Previous clinical trials have suggested that the Chinese Tuina massage may exert transient analgesic effects. However, further investigation regarding the underlying mechanism has been hindered by the lack of a suitable animal model of pain. The present study established a rat model of hind leg pain by injecting 5.8% hypertonic saline solution (HSS) into the left gastrocnemius muscle. The effects of various Tuina massages on the pain thresholds of the rats were then measured. In addition, the effects of ipsilateral and contralateral Tuina massages on C-fiber-evoked field potentials following electrical stimulation of the left sciatic nerve were determined. Alterations in the gastrocnemius muscle tissues following various Tuina applications were investigated using hematoxylin and eosin, and desmin staining, as well as malondialdehyde and superoxide dismutase assays. Heavy hand pressure transiently reduced the pain sensitivity of both posterior limbs, despite HSS only being injected into the left hind leg. Tuina massage treatments that lasted for 15 min were associated with the best results and an absence of local tissue changes. The results of electrical sciatic nerve stimulation demonstrated that ipsilateral and contralateral Tuina massage may decrease the level of peripheral nociceptive C-fiber activity. In the present study, the Chinese Tuina massage exerted analgesic effects in a rat model of pain, which did not involve tissue damage, following a 15 min massage. Therefore, the rat model of pain used in the present study may provide a novel approach for investigating the molecular and physiological mechanisms underlying the therapeutic effects of Tuina massage.