Pharmacological intervention for chronic phase of spinal cord injury

Spinal cord injury is an intractable traumatic injury. The most common hurdles faced during spinal cord injury are failure of axonal regrowth and reconnection to target sites. These also tend to be the most challenging issues in spinal cord injury. As spinal cord injury progresses to the chronic phase, lost motor and sensory functions are not recovered. Several reasons may be attributed to the failure of recovery from chronic spinal cord injury. These include factors that inhibit axonal growth such as activated astrocytes, chondroitin sulfate proteoglycan, myelin-associated proteins, inflammatory microglia, and fibroblasts that accumulate at lesion sites. Skeletal muscle atrophy due to denervation is another chronic and detrimental spinal cord injury–specific condition. Although several intervention strategies based on multiple outlooks have been attempted for treating spinal cord injury, few approaches have been successful. To treat chronic spinal cord injury, neural cells or tissue substitutes may need to be supplied in the cavity area to enable possible axonal growth. Additionally, stimulating axonal growth activity by extrinsic factors is extremely important and essential for maintaining the remaining host neurons and transplanted neurons. This review focuses on pharmacotherapeutic approaches using small compounds and proteins to enable axonal growth in chronic spinal cord injury. This review presents some of these candidates that have shown promising outcomes in basic research(in vivo animal studies) and clinical trials: AA-NgR(310)ecto-Fc(AXER-204), fasudil, phosphatase and tensin homolog protein antagonist peptide 4, chondroitinase ABC, intracellular sigma peptide,(-)-epigallocatechin gallate, matrine, acteoside, pyrvate kinase M2, diosgenin, granulocyte-colony stimulating factor, and fampridine-sustained release. Although the current situation suggests that drug-based therapies to recover function in chronic spinal cord injury are limited, potential candidates have been identified through basic research, and these candidates may be subjects of clinical studies in the future. Moreover, cocktail therapy comprising drugs with varied underlying mechanisms may be effective in treating the refractory status of chronic spinal cord injury.

Matrine promotes neural circuit remodeling to regulate motor function in a mouse model of chronic spinal cord injury

In chronic phase of spinal cord injury, functional recovery is more untreatable compared with early intervention in acute phase of spinal cord injury. In the last decade, several combination therapies successfully improved motor dysfunction in chronic spinal cord injury. However, their effectiveness is not sufficient. We previously found a new effective compound for spinal cord injury, matrine, which induced axonal growth and functional recovery in acute spinal cord injury mice via direct activation of extracellular heat shock protein 90. Although our previous study clarified that matrine was an activator of extracellular heat shock protein 90, the potential of matrine for spinal cord injury in chronic phase has not been sufficiently evaluated. Thus, this study aimed to investigate whether matrine ameliorates chronic spinal cord injury in mice. Once daily intragastric administration of matrine(100 μmol/kg per day) to spinal cord injury mice were starte at 28 days after injury, and continued for 154 days. Continuous mat rine treatment improved hindlimb motor function in chronic spinal cord injury mice. In injured spinal cords of the matrine-treated mice, the density of neurofilament-H-positive axons was increased. Moreover, matrine treatment increased the density of bassoon-positive presynapses in contact with choline acetyltransferase-positive motor neurons in the lumbar spinal cord. These findings suggest that matrine promotes remodeling and reconnection of neural circuits to regulate hindlimb movement. All protocols were approved by the Committee for Animal Care and Use of the Sugitani Campus of the University of Toyama(approval No. A2013 INM-1 and A2016 INM-3) on May 7, 2013 and May 17, 2016, respectively.

Use of curcumin in diagnosis,prevention,and treatment of Alzheimer＇s disease

This review summarizes and describes the use of curcumin in diagnosis,prevention,and treatment of Alzheimer＇s disease.For diagnosis of Alzheimer＇s disease,amyloid-β and highly phosphorylated tau protein are the major biomarkers.Curcumin was developed as an early diagnostic probe based on its natural fluorescence and high binding affinity to amyloid-β.Because of its multi-target effects,curcumin has protective and preventive effects on many chronic diseases such as cerebrovascular disease,hypertension,and hyperlipidemia.For prevention and treatment of Alzheimer＇s disease,curcumin has been shown to effectively maintain the normal structure and function of cerebral vessels,mitochondria,and synapses,reduce risk factors for a variety of chronic diseases,and decrease the risk of Alzheimer＇s disease.The effect of curcumin on Alzheimer＇s disease involves multiple signaling pathways：anti-amyloid and metal iron chelating properties,antioxidation and anti-inflammatory activities.Indeed,there is a scientific basis for the rational application of curcumin in prevention and treatment of Alzheimer＇s disease.

Metabolic derivatives of alcohol and the molecular culpritsof fibro-hepatocarcinogenesis:Allies or enemies?

Chronic intake of alcohol undoubtedly overwhelms the structural and functional capacity of the liver by initiating complex pathological events characterized by steatosis,steatohepatitis,hepatic fibrosis and cirrhosis.Subsequently,these initial pathological events are sustained and ushered into a more complex and progressive liver disease,increasing the risk of fibrohepatocarcinogenesis.These coordinated pathological events mainly result from buildup of toxic metabolic derivatives of alcohol including but not limited to acetaldehyde(AA),malondialdehyde(MDA),CYP2E1-generated reactive oxygen species,alcohol-induced gut-derived lipopolysaccharide,AA/MDA protein and DNA adducts.The metabolic derivatives of alcohol together with other comorbidity factors,including hepatitis B and C viral infections,dysregulated iron metabolism,abuse of antibiotics,schistosomiasis,toxic drug metabolites,autoimmune disease and other non-specific factors,have been shown to underlie liver diseases.In view of the multiple etiology of liver diseases,attempts to delineate the mechanism by which each etiological factor causes liver disease has always proved cumbersome if not impossible.In the case of alcoholic liver disease(ALD),it is even more cumbersome and complicated as a result of the many toxic metabolic derivatives of alcohol with their varying liver-specific toxicities.In spite of all these hurdles,researchers and experts in hepatology have strived to expand knowledge and scientific discourse,particularly on ALD and its associated complications through the medium of scientific research,reviews and commentaries.Nonetheless,the molecularmechanisms underpinning ALD,particularly those underlying toxic effects of metabolic derivatives of alcohol on parenchymal and non-parenchymal hepatic cells leading to increased risk of alcohol-induced fibrohepatocarcinogenesis,are still incompletely elucidated.In this review,we examined published scientific findings on how alcohol and its metabolic derivatives mount cellular attack on each hepatic cell and the underlying molecular mechanisms leading to disruption of core hepatic homeostatic functions which probably set the stage for the initiation and progression of ALD to fibro-hepatocarcinogenesis.We also brought to sharp focus,the complex and integrative role of transforming growth factor beta/small mothers against decapentaplegic/plasminogen activator inhibitor-1 and the mitogen activated protein kinase signaling nexus as well as their cross-signaling with toll-like receptormediated gut-dependent signaling pathways implicated in ALD and fibro-hepatocarcinogenesis.Looking into the future,it is hoped that these deliberations may stimulate new research directions on this topic and shape not only therapeutic approaches but also models for studying ALD and fibro-hepatocarcinogenesis.

Comparative Molecular Field Analysis(CoMFA) of Curcumin-related Compounds for Anticancer Activity

Three-dimensional （3D） quantitative structure-activity relationship （QSAR） studies of 44 curcumin-related compounds have been carried out based on our previously reported result for their anticancer activity against pancreas cancer Panc-I cells and colon cancer HT-29 cells. The established 3D-QSAR models from the comparative molecular field analysis （CoMFA） in training set showed not only significant statistical quality, but also satisfying predictive ability, with high correlation coefficient values （R12= 0.911, R22= 0.985） and cross-validation coefficient values （q2= 0.580, q22= 0.722）. Based on the CoMFA contour maps, some key structural factors responsible for anticancer activity of these series of compounds were revealed. The results provide some useful theoretical references for understanding the mechanism of action, designing new curcumin-related compounds with anticancer activity and predicting their activities prior to synthesis.

Identification of key pathways and gene expression in the activation of mast cells via calcium flux using bioinformatics analysis

Mast cells are the main effector cells in IgE-associated allergic disorders,and we have reported that mucosal mast cells(MMCs)play a more important role in the development of food allergy(FA).IgE with antigen or calcium ionophore stimulation can lead to the activation of MMCs via a calcium-dependent pathway.The purpose of the present study was to identify gene signatures with IgE/antigen(dinitrophenyl-bovine serum albumin,DNP-BSA)or calcium ionophore(A23187)on the activation of MMCs.Differentially expressed genes between the two types of samples were identified with microarray analysis.Gene ontology functional and pathway enrichment analyses of differentially expressed genes were performed using the database for annotation,visualization,and integrated discovery software.The results showed that IgE/antigen and A23187 could induce degranulation,increase vacuoles,and elevate the cytosolic calcium concentration in MMCs.Furthermore,GeneChip analysis showed that the same 134 mRNAs were altered with IgE/DNP-BSA and A23187,suggesting that DNP-BSA/IgE and A23187 affect the same signal pathway partly in degranulation.KEGG analysis showed that the data were enriched in NF-κB,TNF,MAPK,transcription factor activity,DNA binding,and nucleic acid binding,suggesting that activation of MMCs is a complex process.The results provide new insights on MMCs activation.

Active component of Isatidis Radixon insulin resistance in diabetes mellitus rat

OBJECTIVE To investigate the role of active component of Isatidis Radix on insulin resistance in the diabetes mellitus rat.METHODS To induce diabetic rat model with long-term high sugar and high fat plus low-dose streptozotocin(25 mg·kg-1).Then rats were randomly divided into 6 groups:control group,model group,rosiglitazone maleate group(0.3mg·kg-1),high(100mg·kg-1),middle(50mg·kg-1)and low(25 mg·kg-1)active component of Isatidis Radix group.Drugs were adiministered orally once a day.After four weeks,following substances were measured:serum fasting blood glucose,total cholesterol,triglycerides,high density lipoprotein,low density lipoprotein,free fatty acids,fasting insulin,insulin index,pathological observation and immunohistochemistry technology of pancreas islet.RESULTS High and middle active component of Isatidis Radix group could decrease serum FBG,TC,TG,LDL,FFA,FINS and increase serum HDL,ISI;the damage of the pancreas islet has been restoration partly.CONCLUSION Active component of Isatidis Radix could improve insulin resistance in diabetic rats,which might be related to improvement of the function of pancreas islet.

Potent water extracts of Indonesian medicinal plants against PTP1B

Objective:To examine the potent of water as a solvent agent in the preparation of traditional herbal medicine.Methods:Water extracts of 18 plants were prepared through reflux and examined(25μg/mL) to evaluate their possibility for inhibiting protein tyrosine phosphatase 1B(PTP1B).The determination of IC50 values was performed for the samples possessing more than 80%inhibition.Meanwhile,those exhibiting IC50 values more than 7.0 μg/mL were further profiled for their chemical constituents through nuclear magnetic resonance(NMR) measurement.Results:About 44%(8) of the examined samples showed more than 80%inhibition against PTP1 B.The water extracts of Elephantopus scaber,Helicteres isora aerial parts,Elaeocarpus grandiflorus(E.grandiflorus) fruits,Melaleuca leucadendron leaves,and Quercus infectoria gum had IC50 values ranging from 2.05 to 6.90 μg/mL.Meanwhile,Andropogon nardus and Centella asiatica were at the area of δ 3.0-4.0 ppm.Further,the13 C NMR observation of samples possessing the most intensive signals in their proton NMR Cinnamomum burmannii and E.grandiflorus showed the peaks at the area of δ 60-90 ppm as the supportive evidence for sugar group signals.Intriguingly,a disaccharide from E.grandiflorus could be an active inhibitor towards PTB1 B.Conclusions:In contrast to the mainstream solvents currently used in modern herbal manufactures especially Jamu medicine in Indonesia,pure-water-extracted materials should be reconsidered and could be reemerged for future studies and for the manufacture of herbal medicines.In addition,the activity of Jamu components should be confirmed that their antidiabetes and antiobesity activities could be through the inhibition of PTP1 B.

Anti-tumor effects of VnA in in vitro cultured Colon26-L5 cells and in vivo Colon26-L5 cells planted mice

Objective To investigate the antitumor effects of VnA,the total alkaloids isolated from Veratrum Nigrum L.var.ussuriense Nakai("Wusuli Lilu" in Chinese),and the underlying mechanisms with emphasis on its anti-metastatic effects.Methods The effects of VnA on in vitro proliferation,invasion,migration and adhesion in Colon26-L5 cells were investigated.The effect of VnA on experimental lung metastasis of Colon26-L5 cells in mice was also be studied by means of measuring the numbers of tumor colonies in lungs after single i.v.administration of Colon26-L5 cells to mice followed by q.d.i.p VnA for consecutive 14 days.The effect of VnA on the production of matrix metalloproteinases(MMPs)from Colon26-L5 cell in vitro was determined by means of gelatin zymography.Results In in vitro experiments,VnA was found to significantly reduce the number of tumor colonies at dosage of 20.0-40.0 μg·kg-1.In in vitro experiments,VnA inhibited the adhesion(at 1.6-12.5 μg·mL-1)and migration(at 3.1-50.0 μg·mL-1)of Colon26-L5 cell to extracellular matrix components and suppressed invasion into reconstituted basement membrane matrigel(at 3.1-50.0 μg·mL-1),meanwile cell proliferation(at 25.0-50.0 μg·mL-1)was attenuated.VnA also showed a concentration-dependent inhibition of MMP2 and MMP9 production(at 3.1-50.0 μg·mL-1).Conclusions VnA has anti-metastatic protential by decreasing invasiveness of cancer cells as one of its anti-tumor pharmacological effects.

Anti-sickling Activity of Ursolic Acid Isolated from the Leaves of Ocimum gratissimum L.(Lamiaceae)

The present study reports in vitro anti-sickling activity and phytochemical analyses of the leaves of Ocimum gratissimum.Biological testing revealed that the plant extracts possess antisickling effects.The combination of spectroscopic techniques:1D-NMR,2D-NMR and MS revealed that ursolic acid is the major biologically active compound of O.gratissimum(Silva et al.in Molecules 13:2482–2487,2008;Kedar et al.J Food Drug Anal 20:865–871,2012).This study is the first report of the antisickling activity of ursolic acid isolated from O.gratissimum.The pharmaceutical relevance of findings from this study derives from the possibility of integrating O.gratissimum as an antisickling plant in the pharmacopoeia of Democratic Republic of the Congo.The identification of the active principle could enhance the standardization of antisickling recipe.

Anti-inflammatory Activity of Phenolic Acids on HAECs Induced by TNF-α

[Objectives] To study the anti-inflammatory activity and mechanism of salvianolic acid A(Sal A), salvianolic acid C(Sal C), and rosmarinic acid(RA) on HAECs induced by TNF-α. [Methods] VE was used as a positive control and TNF-α induced human aortic endothelial cells(HAECs) were selected as the inflammation model cells. The levels of IL-6, MCP-1 were determined using ELISA. The mRNA levels of IL-6, MCP-1, ICAM-1, P-selectin and NF-κB were analyzed by quantitative RT-PCR. The protein expression of NF-κB was determined by western blot. The adhesion of U937 to HAECs was assessed by BCECF/AM labeling assay. Immunohistochemistry detection was used for ICAM-1 and P-selectin expression levels in TNF-induced HAECs, and DHE detection for the ROS production in HAECs induced by TNF-α. [Results] TNF-α-induced over-expressions of IL-6, MCP-1, NF-κB, ICAM-1 and P-selectin in HAECs were down-regulated by Sal A, Sal C and RA both in mRNA or protein levels, respectively. Meanwhile Sal A, Sal C and RA could significantly inhibit the production of ROS and U937 cells adhesion to HAECs. [Conclusions] Phenolic acids could inhibit TNF-α-induced inflammatory responses on HAECs and the mechanism might be related to inhibition of the production of ROS and blocking NF-κB signaling pathway.

Ginsenoside Rg1 protects against ischemia-induced neuron damage by regulating the rno-miRNA-27a-3p/PPARγaxis

A preliminary miRNA screening showed that expression levels of rno-miRNA-27a-3p were significantly increased in the serum and brain tissues of rats undergoing cerebral ischemia.In recent years,there is evidence of the protective capacity of the saponins extracted from panax ginseng and its primary active ingredient ginsenosideRg1oncerebral ischemic injury.Methods:Fetal rat neurons(FRNs)were cultured in glucose-and-serumfree medium and exposed to hypoxia to establish a cerebral ischemia model in vitro(oxygen and glucose deprivation model,OGD).Antioxidant indexes(CAT,SOD),inflammatory markers(MPO,TNF-αand IL-6),and the expression of apoptosis and proliferation associated proteins(NF kB-p65,Caspase 3-cleaved,BCL-2)were examined.Results:Pre-treatment of Rg1(30–100μg/mL)could effectively inhibit the decline of antioxidant indexes(CAT,SOD)and increase in inflammatory markers(MPO,TNF-αand IL-6),and effectively inhibited the apoptosis in FRNs induced by OGD in a gradient-dependent manner.The mechanism analysis showed that the role of Rg1 in protecting against ischemia-induced neuron damage depends on its indirect up-regulation of PPAR protein via suppression of rnomiRNA-27a-3p.Moreover,these effects of Rg1 could be reversed by exogenous rno-miRNA-27a-3p and PPAR gene silencing in FRNs exposed to OGD.Conclusion:To summarize,our study demonstrates that Rg1 could effectively attenuate neuronal damage caused by cerebral ischemia via the rno-miRNA-27a-3p/PPARγpathway.Further,clarification of the novel mechanism will certainly improve our previous understanding of the role of Rg1 and enhancing its level in treatments for alleviating ischemic brain injury.

Synthesis and pharmacological properties of naturally occurring prenylated and pyranochalcones as potent anti-inflammatory agents

An efficient approach has been developed for the synthesis of naturally occurring prenylated chalcones viz. kanzonol C （1）, stipulin （2）, crotaorixin （3）, medicagenin （4）, licoagrochalcone A （5） and abyssinone D （6） along with the pyranochalcones paratocarpin C （7）, anthyllisone （8） and 3-O-methylabyssinone A （9）. The key step of the synthesis is a Claisen-Schmidt condensation. Subsequently, their anti-inflammatory effects were investigated in lipopolysaccharides （LPSs）-induced RAW-264.7 macrophages. Of the synthesized chalcones, compounds 5 （IC50= 10.41 μmol[L）, 6 （IC50= 9.65 μmol/L） and 8 （IC50= 15.34 μmol/L） show remarkable activity with no cytotoxicity. Compound 9 （IC50 = 4.5 μmol/L） exhibits maximum （83.6%） nitric oxide （NO） inhibition, but shows slight cytotoxicity. The results reveal that the chalcones bearing the prenyl group at 3- and/or 5-position on ring A （acetophenone moiety）, i.e., 1-4 and 7 show weak, or no inhibition activity, whereas chalcones having the prenyl group only on ring B （aldehyde part）, i.e., 5, 6 and 8 show significant activity on the production of inflammatory mediated NO with no cytotoxicity.

Hypothyroid effects on astrocytes and microglia in the adult rat hippocampus

BACKGROUND： Thyroid hormones modulate proliferation of astrocytes and microglia depending on maturation stage and localization. Studies have demonstrated that triiodothyronine treatment or thyroidectomy during developmental stages results in morphological alterations and changes in the number of astrocytes and microglia. Little is known about the effects of hypothyroidism on astrocytes and microglia in adults. OBJECTIVE： To investigate the effects of hypothyroidism on morphology and number of astrocytes and microglia in the adult rat hippocampus. DESIGN, TIME AND SETTING： A randomized, controlled, neuroendocrinological, animal study was performed at the College of Medicine, Hallym University, South Korea between May 2008 and April 2009. MATERIALS： Methimazole, rabbit anti-glial fibrillary acidic protein （GFAP） antiserum, and rabbit anti-lba-1 antiserum were purchased from Sigma, USA. Rabbit anti-GFAP polyclonal antibody was provided by Chemicon, USA. Rabbit anti-lba-1 polyclonal antibody was purchased from Wako, Japan. Terminal deoxynucleotidyl transferase dUTP-biotin nick-end-labeling （TUNEL） kit was provided by Roche Molecular Biochemicals, Mannheim, Germany. METHODS： Hypothyroidism was induced in Wistar rats via methimazole administration （0.025%） in drinking water for 5 weeks, starting at 6 months of age. MAIN OUTCOME MEASURES： Following methimazole treatment, hippocampai neuronal death was determined using TUNEL staining. The morphology and number of GFAP and lba-1 immunoreactive cells were detected by immunohistochemistry. Hippocampal GFAP and lba-1 protein levels were detected by Western blot analysis. Serum-free triiodothyronine and thyroxine levels were quantified. RESULTS： TUNEL-positive neurons were not observed in the hippocampus of euthyroid and hypothyroid rats. Compared with the euthyroid rats, the number of GFAP immunoreactive astrocytes was decreased, and serum triiodothyronine and thyroxine levels were significantly decreased. In contrast, the number of lba-1 immunoreactive microglia was significantly increased in the hypothyroid rats （P 〈 0.05）. In addition, GFAP immunoreactive astrocytes were morphologically at a resting state, and lba-1 immunoreactive microglia were morphologically hypertrophic. GFAP and IBa-1 protein changes in the hippocampus of euthyroid and hypothyroid rats were in accordance with immunohistochemical data. CONCLUSION： Although methimazole-induced hypothyroidism did not induce neuronal injury in the adult rat hippocampus, it did result in decreased astrocyte numbers and increased microglial hypertrophy.

Author correction to"Neutralization of SARSCoV-2 pseudovirus using ACE2-engineered extracellular vesicles"[Acta Pharmaceutica Sinica B 12(2022)1523-1533]

The authors regret in the initially published version of this article,there is a misapplied image in Fig.3C.The corrected Fig.3 is provided below.

Analysis of aristolochic acids, aristololactams and their analogues using liquid chromatography tandem mass spectrometry

More than 80 aristolochic acids(AAs) and aristololactams(ALs) have been found in plants of the Aristolochiaceae family, but relatively few have been fully studied. The present study aimed at developing and validating a liquid chromatography tandem mass spectrometry(LC/MS^n) for the analysis of these compounds. We characterized the fragmentation behaviors of 31 AAs, ALs, and their analogues via high performance liquid chromatography coupled with electrospray ionization mass spectrometry. We summarized their fragmentation rules and used these rules to identify the constituents contained in Aristolochia contorta, Ar. debilis, Ar. manshurensis, Ar. fangchi, Ar. cinnabarina, and Ar. mollissima. The AAs and ALs showed very different MS behaviors. In MS1 of AAs, the characteristic pseudomolecular ions were [M + NH_4]^+, [M + H]^+, and [M + H - H_2O]^+. However, only [M + H]^+ was found in the MS1 of ALs, which was simpler than that of AAs. Distinct MSn fragmentation patterns were found for AAs and ALs, showing the same skeleton among the different substituent groups. The distribution of the 31 constituents in the 6 species of Aristolochia genus was reported for the first time. 25 Analogues of AAs and ALs were detected in this genus. A hierarchical schemes and a calculating formula of the molecular formula of these nitrophenanthrene carboxylic acids and their lactams were proposed. In conclusion, this method could be applied to identification of similar unknown constituents in other plants.

Anti-inflammatory effects of traditional mixed extract of medicinal herbs(MEMH)on monosodium urate crystal-induced gouty arthritis

Korean oriental medicine prescription is widely used for the treatment of gouty diseases. In the present study, we investigated anti-inflammatory effects of modified Korean herbal formulation, mixed extract of medicinal herbs(MEMH), and its modulatory effects on inflammatory mediators associated with gouty arthritis. Both in vitro and in vivo studies were carried out to assess the anti-inflammatory efficacy of MEMH on monosodium urate(MSU) crystals-induced gouty inflammation. MSU crystals stimulated human chondrosarcoma cell line, SW1353, and human primary chondrocytes were treated with MEMH in vitro. The expression levels of pro-inflammatory mediators and metalloproteases were analyzed. The effect of MEMH on NFκB signaling pathway in SW1353 cells was examined. Effect of MEMH on the mR NA expression level of pro-inflammatory mediators and chemotactic factor from human monocytic cell line, THP-1, was also analyzed. The probable role of MEMH in the differentiation process of osteoblast like cells, SaO S-2, after MSU treatment was also observed. To investigate the effects of MEMH in vivo, MSU crystals-induced ankle arthritic model was established. Histopathological changes in affected joints and plasma levels of pro-inflammatory mediators(IL-1β and TNFα) were recorded. MEMH inhibited NFκB signaling pathway and COX-2 protein expression in chondrocytes. MSU-induced mR NA expressions of pro-inflammatory mediators and chemotactic cytokines were suppressed by MEMH. In MSU crystals-induced ankle arthritic mouse model, administration of MEMH relieved inflammatory symptoms and decreased the plasma levels of IL-1β and TNFα. The results indicated that MEMH can effectively inhibit the expression of inflammatory mediators in gouty arthritis, demonstrating its potential for treating gouty arthritis.

Simultaneous analysis of Cu and Pb as ABEDTA complexes in Rhizoma coptidis by capillary electrophoresis coupled with solid phase extraction

A novel capillary electrophoresis method for simultaneous determination of Cu and Pb has been developed in this paper.Cu（Ⅱ） and Pb（Ⅱ） ions were reacted with ABEDTA to form complex to achieve an ideal sensitivity of heavy metal complexes.The digestion solution of Rhizoma coptidis drug sample was purified by neutral Al_2O_3 column chromatography and the chromatographic behavior of metal-L complexes was investigated.The calibration curve was linear in the range of 5-60μg/mL for Cu^（2＋） and 5-25μg/mL for Pb^（2＋） with the correlation coefficients 0.9970 and 0.9972 for each（n = 5）.The average recoveries were 86.2%for Pb and 90.1%for Cu,while the relative standard deviations were 5.1%and 3.6%respectively.The method was successfully applied to determine Cu and Pb in R.coptidis drug samples.

Neutralization of SARS-CoV-2 pseudovirus using ACE2-engineered extracellular vesicles

The spread of coronavirus disease 2019(COVID-19)throughout the world has resulted in stressful healthcare burdens and global health crises.Developing an effective measure to protect people from infection is an urgent need.The blockage of interaction between angiotensin-converting enzyme 2(ACE2)and S protein is considered an essential target for anti-severe acute respiratory syndrome coronavirus 2(SARS-Co V-2)drugs.A full-length ACE2 protein could be a potential drug to block early entry of SARS-Co V-2 into host cells.In this study,a therapeutic strategy was developed by using extracellular vesicles(EVs)with decoy receptor ACE2 for neutralization of SARS-Co V-2.The EVs embedded with engineered ACE2(EVs-ACE2)were prepared;the EVs-ACE2 were derived from an engineered cell line with stable ACE2 expression.The potential effect of the EVs-ACE2 on anti-SARS-Co V-2 was demonstrated by both in vitro and in vivo neutralization experiments using the pseudovirus with the S protein(S-pseudovirus).EVs-ACE2 can inhibit the infection of S-pseudovirus in various cells,and importantly,the mice treated with intranasal administration of EVs-ACE2 can suppress the entry of S-pseudovirus into the mucosal epithelium.Therefore,the intranasal EVs-ACE2 could be a preventive medicine to protect from SARS-Co V-2 infection.This EVs-based strategy offers a potential route to COVID-19 drug development.