Background:Explore the anti-tumor mechanism of herb pair Pinellia ternate-Magnolia officinalis(BX-HP)in liver cancer through network pharmacology using molecular docking methods.Method:The active ingredients and corre...Background:Explore the anti-tumor mechanism of herb pair Pinellia ternate-Magnolia officinalis(BX-HP)in liver cancer through network pharmacology using molecular docking methods.Method:The active ingredients and corresponding targets of the herb pair Pinellia ternate-Magnolia officinalis were obtained from the HERB database.The relevant targets for liver cancer were obtained from GeneCards,DisGeNET,TTD,and Drugbank databases.Obtain common targets between herb pair Pinellia ternate-Magnolia officinalis and liver cancer through the Bioinformatics platform,establish a PPI network diagram using STRING software,and perform GO functional enrichment and KEGG pathway enrichment analysis on the DAVID platform.AutoDockTools 1.5.7 software and molecular dynamics simulation analysis are used to evaluate the binding of components to target proteins.HERB database,SwissTargetPrediction database,SwissADME database,UniProt database,GeneCards database,TTD database,DRUGBANK database,DisGeNET database,String,DAVID.Bioinformatics platform,PDB database,PubChem and TCMSP database.Result:A total of 22 active ingredients with a Probability>0.1 targets in Magnolia officinalis were screened,26 active ingredients with a Probability>0.1 targets in Pinellia ternata,ten vital active ingredients,corresponding to 979 and 803 targets with a Probability>0.1 targets,2536 liver cancer-related targets,and 279 targets in the herb pair Pinellia ternata-Magnolia officinalis.The GO functional enrichment analysis resulted in 1297 entries,namely 971 biological process entries,118 cell localization entries,and 208 molecular function entries.Three signaling pathways were annotated through the KEGG pathway.Based on molecular docking,ten vital active ingredients and five target proteins were validated to exhibit an excellent binding affinity.The above data indicates that combining the herb pair Pinellia ternata-Magnolia officinalis may treat liver cancer through specific targets and signaling pathways.Conclusion:Herb pair Pinellia ternata-Magnolia officinalis has a synergistic effect on treating liver cancer through multicomponent,multitarget,and multi-pathway approaches.This study provides a sufficient theoretical basis for subsequent research.展开更多
Objective:To investigate the therapeutic efficacy and underlying mechanisms of LiZhong Tang in the context of non-alcoholic fatty liver disease(NAFLD).Methods:High-fat feed was used to induce NAFLD in rats,Blood and l...Objective:To investigate the therapeutic efficacy and underlying mechanisms of LiZhong Tang in the context of non-alcoholic fatty liver disease(NAFLD).Methods:High-fat feed was used to induce NAFLD in rats,Blood and liver samples were collected to facilitate a comparative analysis of rat body mass and liver wet weight and calculate the liver index.Liver pathology was observed,while serum transaminase and blood lipid levels were measured.The protein expression levels of PINK1,Parkin,and LC-3II in rat liver were detected using Western Blot analysis.Results:Compared with the control group,the NAFLD rats exhibited a significant increase in body weight,liver wet weight,liver index,transaminase levels,and blood lipid levels.The expression levels of PINK1,Parkin,and LC3-II protein were significantly decreased(P<0.01).Following intervention with Lizhong Tang,rats in each herbal treatment group displayed a decrease in body weight,liver wet weight,liver index,se-rum transaminase,and blood lipid levels.The expression levels of PINK1,Parkin,and LC-3II rebounded(P<0.05),with the high-dose group demonstrating the most pronounced effects(P<0.01).Histopathological examination of liver tissue revealed that rats in the model group displayed disrupted hepatic lobule structure,swollen hepatocytes,disordered arrangement,and a multi-tude of varying-sized lipid vacuoles within the cytoplasm.Conversely,rats treated with different doses of the herbal remedy exhibited improvements in liver tissue pathology,with the high-dose group showing the most notable enhancement.Conclusion:Lizhong Tang can improve NAFLD disease by regulating mitochondrial autophagy.展开更多
With a long industrial chain and a powerful ability to drive other industries,the automobile manufacturing industry has a prominent strategic position in the national economy.In recent years,many countries have put on...With a long industrial chain and a powerful ability to drive other industries,the automobile manufacturing industry has a prominent strategic position in the national economy.In recent years,many countries have put on their agenda the digitalization of the automobile manufacturing industry,leading to an connected,autonomous,shared,and electric(also known as CASE)①development trend in the industry.As one of the six major automobile industry clusters in China,the Chengdu-Chongqing economic circle has achieved initial results in the digital transformation of the automobile manufacturing industry.However,the region is still faced with some constraints,such as insufficient digital infrastructure,relatively slow development of new automobile products,insufficient innovation ability of the automobile industry,and complex digital transformation of small and medium-sized automobile enterprises(automobile SMEs).This paper intends to construct a framework for the mechanism of action of the digital transformation in the automobile manufacturing industry,analyze the effects of the digital transformation of the automobile manufacturing industry in the Chengdu-Chongqing economic circle,and propose feasible paths for the digital transformation of the automobile manufacturing industry in the region by drawing on domestic and international experience in this regard.The specific paths include:(a)Smoothing the“dual-core”data chain to facilitate the digital transformation of the automobile manufacturing industry;(b)Developing the new energy vehicle(NEV)industry to upgrade the quality of automobile products;(c)Achieving corner overtaking in the digital transformation of the automobile manufacturing industry with digital technology;(d)Jointly building the automobile industrial park to promote the digital transformation of the industry;(e)Addressing problems facing automobile SMEs in digital transformation via targeted policy tools.展开更多
Objective:To study the mechanism of action and therapeutic effect of modified Qiwei Baishu powder in diabetic patients.Methods:From January 2021 to January 2022,80 diabetic patients were recruited in our study and div...Objective:To study the mechanism of action and therapeutic effect of modified Qiwei Baishu powder in diabetic patients.Methods:From January 2021 to January 2022,80 diabetic patients were recruited in our study and divided into two groups by the random number table method.Group A was treated with modified Qiwei Baishu powder,whereas group B was treated with western medicine.The therapeutic effect,traditional Chinese medicine(TCM)syndrome score,blood sugar level,and incidence of adverse reaction were compared between the two groups.Result:The therapeutic effect in group A was significantly higher than that in group B(P<0.05);the TCM syndrome scores of group A were significantly lower than those of group B(P<0.05);the fasting blood glucose(FBG),2 hour-postprandial blood glucose(PBG),and glycosylated hemoglobin(HbA1c)levels of group A were significantly lower than those of group B(P<0.05);the incidence of adverse reaction in group A was significantly lower than that in group B(P<0.05).Conclusion:On the basis of western medicine,the addition of modified Qiwei Baishu powder can maintain stable blood sugar levels in patients and alleviate diabetic symptoms;thus,it is not only effective,but also safe for clinical use in diabetes.展开更多
Background:The aim of this study is to explore the mechanism by which Wuzhuyu Decoction treats vascular headache.Methods:We utilized the TCMSP database to identify active ingredients and targets of the Chinese herbal ...Background:The aim of this study is to explore the mechanism by which Wuzhuyu Decoction treats vascular headache.Methods:We utilized the TCMSP database to identify active ingredients and targets of the Chinese herbal medicine,and the Gendcars,OMIM,PharmGKB,TTD,and DrugBank databases were used to screen for disease targets.We constructed the PPI network of targets by utilizing the String database,and GO and KEGG analyses were performed.The"drug-ingredient-target-disease"network diagram was constructed using Cytoscape 3.8.0 software.We analyzed the topological parameters to identify the primary active ingredients and targets of Wuzhuyu Decoction,and subsequently confirmed the findings via molecular docking.Results:A total of 86 active ingredients were obtained,including Quercetin,Kaempferol,Beta-sitosterol,Stigmasterol,and Nuciferin.Fourteen core targets were identified,including JUN,TP53,AKT1,RELA,MAPK1,MAPK14,MYC,MAPK8,CCND1,ESR1,CTNNB1,FOS,NR3C1,and RB1.GO enrichment analysis involved biological processes such as response to drug,response to lipopolysaccharide,and response to molecule of bacterial origin.The cellular components were membrane raft and membrane microdomain,and the molecular functions were catecholamine binding and nuclear receptor activity.The KEGG pathway enrichment analysis demonstrated the potential regulation of 171 pathways by Wuzhuyu Decoction.including the Lipid and atherosclerosis signaling pathway,the Fluid shear stress and atherosclerosis signaling pathway,and the PI3K-AKT signaling pathway.Molecular docking showed that Nuciferin had good binding activity with AKT1(-9.9 kJ/mol),as did Quercetin with AKT1(-9.8 kJ/mol),Stigmasterol with MAPK1(-9.7 kJ/mol),and Kaempferol with AKT1(-9.5 kJ/mol).Conclusion:Wuzhuyu Decoction may exert its therapeutic effect on vascular headache by inhibiting neurogenic inflammation,providing analgesia,and modulating the immune system.展开更多
Pituitary tumors are common intracranial tumors,but when faced with drugresistant or aggressive tumors,existing medical measures may not provide good control,leading to progression and deterioration.Metformin,a tradit...Pituitary tumors are common intracranial tumors,but when faced with drugresistant or aggressive tumors,existing medical measures may not provide good control,leading to progression and deterioration.Metformin,a traditional hypoglycemic drug,has recently been discovered to have multiple functions including antitumor effects.There have been studies on the mechanism of metformin for the treatment of pituitary tumors,but it is uncertain whether it will provide new adjuvant or alternative therapies for the treatment of these tumors.We analyzed the potential mechanisms of action of metformin with respect to the inhibition of pituitary tumor growth and hormone secretion by reviewing the available literature.展开更多
Objective:The aim of this study is to explore the active ingredients and mechanism of action of danhong injection(DHI)in treating myeloproliferative neoplasms using network pharmacology.Methods:The TCMSP platform and ...Objective:The aim of this study is to explore the active ingredients and mechanism of action of danhong injection(DHI)in treating myeloproliferative neoplasms using network pharmacology.Methods:The TCMSP platform and relevant literature were used to search for the active ingredients and targets of Radix Salviae and Carthami Flos in DHI.Disease targets related to myeloproliferative neoplasms were obtained from the GEO database,GeneCards,and DisGeNET database.The queried component targets were normalized using the UniProt database.Potential targets were identified by constructing protein-protein interactions networks using STRING 11.5 and visualized and analyzed using Cytoscape 3.9.1.GO and KEGG analysis were performed using the Metascape platform,and visualization was done using the built-in plug-in CluoGO or SangerBox platforms with Cytoscape 3.9.1.Results:The active ingredients of DHI for treating myeloproliferative neoplasms mainly consist of flavonoids and o-benzoquinones,including quercetin,luteolin,kaempferol,stigmasterol,tanshinone iia,cryptotanshinone,beta-carotene,2-isopropyl-8-methylphenanthrene-3,4-dione,and neocryptotanshinone ii.The potential targets are JUN,TP53,STAT3,AKT1,MAPK1,RELA,TNF,MAPK14,IL6,and FOS.The relevant signaling pathways involved are mainly TNFαsignaling pathway,PI3K-Akt signaling pathway,apoptosis,IL-17 signaling pathway,cellular senescence,MAPK signaling pathway,p53 signaling pathway,JAK-STAT signaling pathway,and NF-kappa B signaling.Conclusions:DHI acts mainly through flavonoids and o-benzoquinones to treat myeloproliferative neoplasms in a multi-targeted and multi-pathway manner.展开更多
Despite that some approved drugs and genetically engineered vaccines against hepatitis B virus(HBV)are available for HBV patients,HBV infection is still a severe public health problem in the world.All the approved the...Despite that some approved drugs and genetically engineered vaccines against hepatitis B virus(HBV)are available for HBV patients,HBV infection is still a severe public health problem in the world.All the approved therapeutic drugs(including interferonalpha and nucleoside analogues)have their limitations.No drugs or therapeutic methods can cure hepatitis B so far.Therefore,it is urgently needed to discover and develop new anti-HBV drugs,especially nonnucleoside agents.Naturally originated compounds with enormous molecular complexity and diversity offer a great opportunity to find novel anti-HBV lead compounds with specific antiviral mechanisms.In this review,the natural products against HBV are discussed according to their chemical classes such as terpenes,lignans,phenolic acids,polyphenols,lactones,alkaloids and flavonoids.Furthermore,novel mode of action or new targets of some representative anti-HBV natural products are also discussed.The aim of this review is to report new discoveries and updates pertaining to anti-HBV natural products in the last 20years,especially novel skeletons and mode of action.Although many natural products with various skeletons have been reported to exhibit potent anti-HBV effects to date,scarcely any of them are found in the list of conventional anti-HBV drugs worldwide.Additionly,in anti-HBV mechanism of action,only a few references reported new targets or novel mode of action of antiHBV natural products.展开更多
The management of bacterial infections is becoming a major clinical challenge due to the rapid evolution of antibiotic resistant bacteria.As an excellent candidate to overcome antibiotic resistance,antimicrobial pepti...The management of bacterial infections is becoming a major clinical challenge due to the rapid evolution of antibiotic resistant bacteria.As an excellent candidate to overcome antibiotic resistance,antimicrobial peptides(AMPs)that are produced from the synthetic and natural sources demonstrate a broad-spectrum antimicrobial activity with the high specificity and low toxicity.These peptides possess distinctive structures and functions by employing sophisticated mechanisms of action.This comprehensive review provides a broad overview of AMPs from the origin,structural characteristics,mechanisms of action,biological activities to clinical applications.We finally discuss the strategies to optimize and develop AMP-based treatment as the potential antimicrobial and anticancer therapeutics.展开更多
Leucine-rich repeat kinase 1 (LRRK1) plays a critical role in regulating cytoskeletal organization, osteoclast activity, and bone resorption with little effect on bone formation parameters. Deficiency of Lrrk1 in mice...Leucine-rich repeat kinase 1 (LRRK1) plays a critical role in regulating cytoskeletal organization, osteoclast activity, and bone resorption with little effect on bone formation parameters. Deficiency of Lrrk1 in mice causes a severe osteopetrosis in the metaphysis of the long bones and vertebrae bones, which makes LRRK1 an attractive alternative drug target for the treatment of osteoporosis and other high-turnover bone diseases.This review summarizes recent advances on the functions of the Lrrk1-related family members, Lrrk1deficiency-induced skeletal phenotypes, LRRK1 structure–function, potential biological substrates and interacting proteins, and the mechanisms of LRRK1 action in osteoclasts.展开更多
Nagilactones are tetracyclic natural products isolated from various Podocarpus species.These lactone-based compounds display a range of pharmacological effects,including antifungal,anti-atherosclerosis,anti-inflammato...Nagilactones are tetracyclic natural products isolated from various Podocarpus species.These lactone-based compounds display a range of pharmacological effects,including antifungal,anti-atherosclerosis,anti-inflammatory and anticancer activities reviewed here.The most active derivatives,such as nagilactones C,E and F,exhibit potent anticancer activities against different cancer cell lines and tumor models.A comprehensive analysis of their mechanism of action indicates that their anticancer activity mainly derives from three complementary action:(i)a drug-induced inhibition of cell proliferation coupled with a cell cycle perturbation and induction of apoptosis,(ii)a blockade of the epithelial to mesenchymal cell transi-tion contributing to an inhibition of cancer cell migration and invasion and(iii)a capacity to modulate the PD-L1 immune checkpoint.Different molecular effectors have been implicated in the antitumor activity,chiefly the AP-1 pathway blocked upon activation of the JNK/c-Jun axis.Nag-C is a potent inhibitor of protein synthesis binding to eukaryotic ribosomes and inhibition of different protein kinases,such as RIOK2 and JAK2,has been postulated with Nag-E.The literature survey on nagilactones highlights the therapeutic potential of these little-known terpenoids.The mechanistic analysis also provides useful information for structurally related compounds(podolactones,oidiolactones,inumakilactones)isolated from Podo-carpus plants.展开更多
Biflavonoids are divided in two classes:C-C type compounds represented by the dimeric compound amentoflavone and C-O-C-type compounds typified by hinokiflavone(HNK)with an ether linkage between the two connected apige...Biflavonoids are divided in two classes:C-C type compounds represented by the dimeric compound amentoflavone and C-O-C-type compounds typified by hinokiflavone(HNK)with an ether linkage between the two connected apigenin units.This later sub-group of bisflavonyl ethers includes HNK,ochnaflavone,delicaflavone and a few other dimeric compounds,found in a variety of plants,notably Selaginella species.A comprehensive review of the anticancer properties and mechanism of action of HNK is provided,to highlight the anti-proliferative and anti-metastatic activities of HNK and derivatives,and HNK-containing plant extracts.The anticancer effects rely on the capacity of HNK to interfere with the ERK1-2/p38/NFκB signaling pathway and the regulation of the expression of the matrix metalloproteinases MMP-2 and MMP-9(with a potential direct binding to MMP-9).In addition,HNK was found to function as a potent modulator of pre-mRNA splicing,inhibit-ing the SUMO-specific protease SENP1.As such,HNK represents a rare SENP1 inhibitor of natural origin and a scaffold to design synthetic compounds.Oral formulations of HNK have been elaborated to enhance its solubility,to facilitate the compound delivery and to enhance its anticancer efficacy.The review shed light on the anticancer potential of C-O-C-type biflavonoids and specifically on the pharmacological profile of HNK.This compound deserves further attention as a regu-lator of pre-mRNA splicing,useful to treat cancers(in particular hepatocellular carcinoma)and other human pathologies.展开更多
Objective:To predict the mechanism of action of San Huang lotion for topical treatment of eczema at the level of network pharmacology and molecular docking technology.Methods:The active ingredients and corresponding t...Objective:To predict the mechanism of action of San Huang lotion for topical treatment of eczema at the level of network pharmacology and molecular docking technology.Methods:The active ingredients and corresponding targets of San Huang lotion were collected using the TCMSP data platform and UniProt;the relevant gene targets of San Huang lotion were collected using the GeneCards database,OMIM database,TTD database,and DrugBank database;the intersection targets of San Huang lotion and eczema were obtained by creating avenn diagram;the key active ingredients and targets were screened by constructing a disease-active ingredient-target map,and the key active ingredients and core targets were screened out by constructing disease-active ingredient-target diagrams and PPInetwork diagrams;GOand KEGGenrichment analyses were conducted using the metascapewebsite and the higher significant entries were selected to produce bar charts and bubble plots.Finally,molecular docking of key active ingredients and core targets was performed.Results:A total of 134 active ingredients and 3,320 eczema-related target genes were screened for San Huang lotion,and 126 intersecting targets were obtained for San Huang lotion and eczema.The five key active ingredients of San Huang lotion for topical treatment of eczema and six core targets ofAKT1,TNF,IL6,IL1B,TP53andVEGFA were obtained by drug-active ingredient-target map and PPInetwork map.The GOand KEGGenrichment analysis showed that the topical treatment of eczema withSanHuanglotion might be mediated throughIL-17signaling pathway,TNFsignaling pathway and Th17cell differentiation pathway.The molecular docking results showed that the docking binding energy of key active ingredients and core targets was mostly less than-5 kcal/mol,and the docking was good.Conclusion:The quercetin,luteolin,wogonin,formononetin,beta-sitosterol and other active ingredients in San Huang lotion may act on eczema through AKT1,TNF,IL6,IL1B,TP53,VEGFA and other targets,and through IL-17signaling pathway,TNFsignaling pathway,Th17cell differentiation and other pathways.展开更多
Objective:To explore the protective effect and possible mechanism of action of Zhuyu Annao pill in mice with intracerebral hemorrhage(ICH).Methods:Sixty mice were divided into the control group,hemorrhage group,drug-t...Objective:To explore the protective effect and possible mechanism of action of Zhuyu Annao pill in mice with intracerebral hemorrhage(ICH).Methods:Sixty mice were divided into the control group,hemorrhage group,drug-treated group(after hemorrhage),TLR4-knockout hemorrhage group and TLR4-knockout hemorrhage + drug-treated group(after hemorrhage) with 12 in each group.Model of autologous ICH was established in all groups.After drilling and 12 h of fasting,models in the control group hemorrhage group and TLR4-knockout hemorrhage group were all drenched with 10 mL/kg distilled water by intragastric administration.Models in the drug-treated group and TLR4-knockout hemorrhage + drugtreated group were drenched with 6.25 g/kg of Zhuyu Annao pill.All groups were treated for 7 d.Longa scoring method was used to measure the neurological defect scores and determine the brain water contents of all groups;ELISA was employed to detect the inflammatory factor interleukin(IL)-6,tumor necrosis factor- α(TNF- α) and IL-1β in brain tissues;and Western blot was applied to test the expression quantities of apoptotic protein Bax and anti-apoptotic protein Bcl-2 in brain tissues.Results:At day 3 and7,compared with the hemorrhage group,the neurological defect scores of the drug-treated group,TLR4-knockout hemorrhage group and TLR4-knockout hemorrhage + drug-treated group decreased significantly(P<0.05) Compared with the hemorrhage group,the brain water contents of the drug-treated group,TLR4-knockout hemorrhage group and TLR4-knockout hemorrhage + drug-treated group reduced significantly(P<0.05) Compared with the hemorrhage group,the inflammatory factor IL-6,TNF-α and IL-1β of the drug-treated group,TLR4-knockout hemorrhage group and TLR4-knockout hemorrhage + drug-treated group decreased significantly(P<0.05).Compared with the hemorrhage group,the expression of apoptotic protein Bax of the drug-treated group,TLR4-knockout hemorrhage group and TLR4-knockout hemorrhage+ drug-treated group decreased significantly and the expression of anti-apoptotic protein Bcl-2 increased significantly(P<0.05).Conclusions:Zhuyu Annao pill can alleviateencephaledema for mice with ICH and reduce inflammatory responsesandnerve cell apoptosis.TLR4 can mediate inflammatory injury induced by ICH.Thus,Zhuyu Annao pill can play a protective role for brains by decreasing the expression of TLR4.展开更多
Objective: To find a natural plant essential oil(EO) with excellent antimicrobial effect on food-borne bacteria and to explore the mechanism of its antimicrobial function against Escherichia coli(E. coli). Methods: Th...Objective: To find a natural plant essential oil(EO) with excellent antimicrobial effect on food-borne bacteria and to explore the mechanism of its antimicrobial function against Escherichia coli(E. coli). Methods: The antimicrobial activity of seven EOs against Gramnegative E. coli ATCC 8739 and Gram-positive Staphylococcus aureus ATCC 6538 was investigated using agar disk diffusion method, and the minimum inhibitory concentration(MIC) and minimum bactericidal concentration(MBC) of each EO was determined using the broth dilution method. The chemical composition of the Trachyspermum copticum(T. copticum) EO was analyzed using gas chromatography–mass spectrometry(GC/MS). In order to explore the mechanism of the antimicrobial action, 1 MIC and 2 MIC of T. copticum EO was added to a suspension of E. coli, the growth curve and the scanning electron microscopy(SEM) analysis of E. coli, and the release of cell constituents and protein and potassium ions from the bacterial cell were measured. Results: The T. copticum EO had the best antimicrobial activity against the test bacteria, and 10 compounds accounting for 94.57% of the total oil were identified, with the major components being thymol(46.22%), p-cymene(19.03%), and 毭-terpinene(22.41%). The addition of 1 MIC T. copticum EO significantly inhibited the growth of E. coliand increased the release of cell constituents and protein and potassium ions from the bacterial cells. Scanning electron micrographs showed that T. copticum EO caused most of the E. colicell membranes to collapse and rupture, leading to cell death. Conclusions: These results indicate that T. copticum EO is a good natural antimicrobial agent for food-borne pathogens.展开更多
This study was conducted to comprehensively evaluate the effects of salicylic acid and sodium molybdate on cold tolerance of an ornamental plant Bougainvillea glabra and to provide a theoretical guidance for landscape...This study was conducted to comprehensively evaluate the effects of salicylic acid and sodium molybdate on cold tolerance of an ornamental plant Bougainvillea glabra and to provide a theoretical guidance for landscape maintenance.B.glabra plants were treated with 0.5 mmol/L salicylic acid and 2.0 μmol/L alone or in combination,and then exposed to low temperature stress before physiological indices were measured.The results showed that all salicylic acid and sodium molybdate treatments reduced the relative conductivity and malondialdehyde( MDA) content of B.glabra to varying extents under the stress of low temperature,and more significant effect was achieved by using the two agents in combination.Oxygen free radicals production rate increased with decreasing temperature from 20 to 6 ℃,but declined with temperature decreasing from 3 to-3 ℃.The SOD activity of the control( CK) was significantly lower than that of other treatments at 0 and-3 ℃.The treatments with salicylic acid and sodium molybdate alone and in combination increased POD activity of B.glabra plants,especially at 0 ℃,as the POD activity of treatments T1,T2 and T3 was significantly higher than that of CK at 0 ℃.In addition,under low temperature stress,the contents of soluble sugar,starch and proline increased initially and decreased subsequently with temperature decreasing.The soluble sugar content at 3 ℃,starch and proline contents at 0 and-3 ℃ in treatments with salicylic acid and sodium molybdate alone and in combination were significantly higher than those of CK.All above results proved that salicylic acid and sodium molybdate are able to improve cold tolerance of B.glabra,and better effect can be achieved by using them together.展开更多
Life expectancy in industrialized and developed countries will continue to increase in the near future. Consequently, over the last years, the incidence and social impact of neurodegenerative diseases have increased, ...Life expectancy in industrialized and developed countries will continue to increase in the near future. Consequently, over the last years, the incidence and social impact of neurodegenerative diseases have increased, highlighting an urgent need for new and more effective therapeutic strategies to counter these terrible disorders. While we tend to think about neurodegenerative diseases as conditions that are uniquely associated with the elder age, these diseases cover a diverse range across the entire lifespan, even affecting infants and children.展开更多
Objective:To predict the potential active ingredients (PAIs) and mechanism of action of traditional Chinese medicine formulations used to delay aging.Methods:We incorporated the use of quantum-chemistry calculations a...Objective:To predict the potential active ingredients (PAIs) and mechanism of action of traditional Chinese medicine formulations used to delay aging.Methods:We incorporated the use of quantum-chemistry calculations and machine learning to predict the active ingredients of some Chinese herbal medicines used to delay aging.Then,a network-pharmacology approach was used to uncover how these PAls delayed aging.Results:Twelve PAls with anti-aging effects were discovered:androsterone,MHP,cortisone,propyl methyl trisulfide,retinol,retinal,cortisol,11-cis-Retinol (2R,3R)-3-hydroxyproline,4,5alpha-Dihydrocortisone (2S)-2-ammonio-6-ureidohexanoate and17alpha,21-Dihydroxy-5beta-pregnane-3,11,20-trione.Enrichment analyses indicated that a putative compound target and aging target were significantly associated with:regulation of the immune system;insulin receptor signaling pathway;regulation of the mitotic cell cycle;response to nutrient levels;response to oxidative stress;release of cytochrome c from mitochondria;learning or memory;inflammatory response.Conclusions:A novel method was proposed to predict the PAls of anti-aging herbal medicines by incorporating quantum-chemistry calculations and machine learning.Then,a network-pharmacology approach was used to uncover how these PAls delay aging.The information provided by our study on PAls may aid the discovery of anti-aging drugs.展开更多
Background: Recently, high efficacy of the chemotherapeutic regimen combining clarithromycin (CAM) with lenalidomide (Len) and dexamethasone (Dex) (BiRD) in treating multiple myeloma (MM) patients has been reported. H...Background: Recently, high efficacy of the chemotherapeutic regimen combining clarithromycin (CAM) with lenalidomide (Len) and dexamethasone (Dex) (BiRD) in treating multiple myeloma (MM) patients has been reported. However, the exact mechanism of added CAM has not been fully elucidated. This case report will provide helpful information for understanding the significance and the mechanism of action of CAM as an add-on therapy. Patient: A 78-year-old female patient with IgA-λ type MM was treated with low-dose Len coupled with low-dose Dex (low Rd), and excellent response was achieved for long term, but she later became refractory to this treatment. Then, CAM was added to low Rd (low Rd-CAM, i.e., modified BiRD therapy). This add-on-therapy was found to be effective, but later suspended because of pneumonitis. Then, low-dose Len coupled with CAM (low R-CAM) treatment was applied;but effect of this Dex-free treatment was insufficient. Thus, low Rd-CAM was reapplied and satisfactory reduction of IgA was achieved. This fact suggests that low Rd-CAM is the favorable combination, Dex is requisite and CAM might have enhanced the effect of Dex. In this case, various serum cytokines were examined during the course of illness. Only interleukin-6 showed apparent increase, and tumor necrosis factor-α, transforming growth factor-β, soluble IL-2 receptors and C-reactive protein showed the slight increase during low Rd-CAM treatment. The results seem somewhat conflicting, but it seems that intricate cytokine response due to immune activation might have occurred during low Rd-CAM treatment.展开更多
Plants from the genus Cannabis,and strains of Cannabis sativa in particular,have been used in medicine since ancient times.The Cannabis plant contains more than 500 chemical compounds,with two main phytocannabinoids c...Plants from the genus Cannabis,and strains of Cannabis sativa in particular,have been used in medicine since ancient times.The Cannabis plant contains more than 500 chemical compounds,with two main phytocannabinoids consisting of Δ9-tetrahydrocannabinol(THC),the psychoactive constituent,and cannabidiol(CBD),which does not bear this effect.This paper aims at providing a perspective on the potential therapeutic effects of CBD based on its preferential interaction with transient potential receptor V2(TRPV2).Many formulations based on Cannabis extract have been licensed for therapeutic use in some Western countries.Among these,the most relevant are Sativex(THC+CBD,used mainly for the treatment of spasticity in multiple sclerosis)and Epidyolex(purified plant-derived CBD,used for some rare childhood epilepsies).展开更多
基金the National Natural Science Foundation of China(No.82204250)China Postdoctoral Science Foundation(No.2021M693961)+2 种基金Young and Middle-Aged Talent Project of Hubei Provincial Department of Education(No.Q20222808)Hubei University of Science and Technology Doctoral Startup Fund Project(No.BK202029)Outstanding Young and Middle-Aged Scientific and Technological Innovation Team in Colleges and Universities in Hubei Province(No.T2021022).
文摘Background:Explore the anti-tumor mechanism of herb pair Pinellia ternate-Magnolia officinalis(BX-HP)in liver cancer through network pharmacology using molecular docking methods.Method:The active ingredients and corresponding targets of the herb pair Pinellia ternate-Magnolia officinalis were obtained from the HERB database.The relevant targets for liver cancer were obtained from GeneCards,DisGeNET,TTD,and Drugbank databases.Obtain common targets between herb pair Pinellia ternate-Magnolia officinalis and liver cancer through the Bioinformatics platform,establish a PPI network diagram using STRING software,and perform GO functional enrichment and KEGG pathway enrichment analysis on the DAVID platform.AutoDockTools 1.5.7 software and molecular dynamics simulation analysis are used to evaluate the binding of components to target proteins.HERB database,SwissTargetPrediction database,SwissADME database,UniProt database,GeneCards database,TTD database,DRUGBANK database,DisGeNET database,String,DAVID.Bioinformatics platform,PDB database,PubChem and TCMSP database.Result:A total of 22 active ingredients with a Probability>0.1 targets in Magnolia officinalis were screened,26 active ingredients with a Probability>0.1 targets in Pinellia ternata,ten vital active ingredients,corresponding to 979 and 803 targets with a Probability>0.1 targets,2536 liver cancer-related targets,and 279 targets in the herb pair Pinellia ternata-Magnolia officinalis.The GO functional enrichment analysis resulted in 1297 entries,namely 971 biological process entries,118 cell localization entries,and 208 molecular function entries.Three signaling pathways were annotated through the KEGG pathway.Based on molecular docking,ten vital active ingredients and five target proteins were validated to exhibit an excellent binding affinity.The above data indicates that combining the herb pair Pinellia ternata-Magnolia officinalis may treat liver cancer through specific targets and signaling pathways.Conclusion:Herb pair Pinellia ternata-Magnolia officinalis has a synergistic effect on treating liver cancer through multicomponent,multitarget,and multi-pathway approaches.This study provides a sufficient theoretical basis for subsequent research.
基金Youth Fund of Guangxi Natural Science Foundat ion (No.2020GXNSFBA297133)Guangxi Traditional Chinese Medicine Administration Science and Technology Project (No.GZSY20-60)+1 种基金Natural Science Youth Fund of Guangxi University of Traditional Chinese Medicine (No.2020QN020)Guangxi Qihuang Scholar Training Project.
文摘Objective:To investigate the therapeutic efficacy and underlying mechanisms of LiZhong Tang in the context of non-alcoholic fatty liver disease(NAFLD).Methods:High-fat feed was used to induce NAFLD in rats,Blood and liver samples were collected to facilitate a comparative analysis of rat body mass and liver wet weight and calculate the liver index.Liver pathology was observed,while serum transaminase and blood lipid levels were measured.The protein expression levels of PINK1,Parkin,and LC-3II in rat liver were detected using Western Blot analysis.Results:Compared with the control group,the NAFLD rats exhibited a significant increase in body weight,liver wet weight,liver index,transaminase levels,and blood lipid levels.The expression levels of PINK1,Parkin,and LC3-II protein were significantly decreased(P<0.01).Following intervention with Lizhong Tang,rats in each herbal treatment group displayed a decrease in body weight,liver wet weight,liver index,se-rum transaminase,and blood lipid levels.The expression levels of PINK1,Parkin,and LC-3II rebounded(P<0.05),with the high-dose group demonstrating the most pronounced effects(P<0.01).Histopathological examination of liver tissue revealed that rats in the model group displayed disrupted hepatic lobule structure,swollen hepatocytes,disordered arrangement,and a multi-tude of varying-sized lipid vacuoles within the cytoplasm.Conversely,rats treated with different doses of the herbal remedy exhibited improvements in liver tissue pathology,with the high-dose group showing the most notable enhancement.Conclusion:Lizhong Tang can improve NAFLD disease by regulating mitochondrial autophagy.
文摘With a long industrial chain and a powerful ability to drive other industries,the automobile manufacturing industry has a prominent strategic position in the national economy.In recent years,many countries have put on their agenda the digitalization of the automobile manufacturing industry,leading to an connected,autonomous,shared,and electric(also known as CASE)①development trend in the industry.As one of the six major automobile industry clusters in China,the Chengdu-Chongqing economic circle has achieved initial results in the digital transformation of the automobile manufacturing industry.However,the region is still faced with some constraints,such as insufficient digital infrastructure,relatively slow development of new automobile products,insufficient innovation ability of the automobile industry,and complex digital transformation of small and medium-sized automobile enterprises(automobile SMEs).This paper intends to construct a framework for the mechanism of action of the digital transformation in the automobile manufacturing industry,analyze the effects of the digital transformation of the automobile manufacturing industry in the Chengdu-Chongqing economic circle,and propose feasible paths for the digital transformation of the automobile manufacturing industry in the region by drawing on domestic and international experience in this regard.The specific paths include:(a)Smoothing the“dual-core”data chain to facilitate the digital transformation of the automobile manufacturing industry;(b)Developing the new energy vehicle(NEV)industry to upgrade the quality of automobile products;(c)Achieving corner overtaking in the digital transformation of the automobile manufacturing industry with digital technology;(d)Jointly building the automobile industrial park to promote the digital transformation of the industry;(e)Addressing problems facing automobile SMEs in digital transformation via targeted policy tools.
文摘Objective:To study the mechanism of action and therapeutic effect of modified Qiwei Baishu powder in diabetic patients.Methods:From January 2021 to January 2022,80 diabetic patients were recruited in our study and divided into two groups by the random number table method.Group A was treated with modified Qiwei Baishu powder,whereas group B was treated with western medicine.The therapeutic effect,traditional Chinese medicine(TCM)syndrome score,blood sugar level,and incidence of adverse reaction were compared between the two groups.Result:The therapeutic effect in group A was significantly higher than that in group B(P<0.05);the TCM syndrome scores of group A were significantly lower than those of group B(P<0.05);the fasting blood glucose(FBG),2 hour-postprandial blood glucose(PBG),and glycosylated hemoglobin(HbA1c)levels of group A were significantly lower than those of group B(P<0.05);the incidence of adverse reaction in group A was significantly lower than that in group B(P<0.05).Conclusion:On the basis of western medicine,the addition of modified Qiwei Baishu powder can maintain stable blood sugar levels in patients and alleviate diabetic symptoms;thus,it is not only effective,but also safe for clinical use in diabetes.
基金supported by the China Natural Science Foundation(No.81973811).
文摘Background:The aim of this study is to explore the mechanism by which Wuzhuyu Decoction treats vascular headache.Methods:We utilized the TCMSP database to identify active ingredients and targets of the Chinese herbal medicine,and the Gendcars,OMIM,PharmGKB,TTD,and DrugBank databases were used to screen for disease targets.We constructed the PPI network of targets by utilizing the String database,and GO and KEGG analyses were performed.The"drug-ingredient-target-disease"network diagram was constructed using Cytoscape 3.8.0 software.We analyzed the topological parameters to identify the primary active ingredients and targets of Wuzhuyu Decoction,and subsequently confirmed the findings via molecular docking.Results:A total of 86 active ingredients were obtained,including Quercetin,Kaempferol,Beta-sitosterol,Stigmasterol,and Nuciferin.Fourteen core targets were identified,including JUN,TP53,AKT1,RELA,MAPK1,MAPK14,MYC,MAPK8,CCND1,ESR1,CTNNB1,FOS,NR3C1,and RB1.GO enrichment analysis involved biological processes such as response to drug,response to lipopolysaccharide,and response to molecule of bacterial origin.The cellular components were membrane raft and membrane microdomain,and the molecular functions were catecholamine binding and nuclear receptor activity.The KEGG pathway enrichment analysis demonstrated the potential regulation of 171 pathways by Wuzhuyu Decoction.including the Lipid and atherosclerosis signaling pathway,the Fluid shear stress and atherosclerosis signaling pathway,and the PI3K-AKT signaling pathway.Molecular docking showed that Nuciferin had good binding activity with AKT1(-9.9 kJ/mol),as did Quercetin with AKT1(-9.8 kJ/mol),Stigmasterol with MAPK1(-9.7 kJ/mol),and Kaempferol with AKT1(-9.5 kJ/mol).Conclusion:Wuzhuyu Decoction may exert its therapeutic effect on vascular headache by inhibiting neurogenic inflammation,providing analgesia,and modulating the immune system.
基金Supported by the Science and Technology Program of Nantong Health Committee,No.MA2019003,No.MA2021017,No.Key003Science and Technology Program of Nantong City,NO.MS12015016,and No.JCZ2022040and Kangda College of Nanjing Medical University,No.KD2021JYYJYB025,No.KD2022KYJJZD019,and No.KD2022KJJZZD022.
文摘Pituitary tumors are common intracranial tumors,but when faced with drugresistant or aggressive tumors,existing medical measures may not provide good control,leading to progression and deterioration.Metformin,a traditional hypoglycemic drug,has recently been discovered to have multiple functions including antitumor effects.There have been studies on the mechanism of metformin for the treatment of pituitary tumors,but it is uncertain whether it will provide new adjuvant or alternative therapies for the treatment of these tumors.We analyzed the potential mechanisms of action of metformin with respect to the inhibition of pituitary tumor growth and hormone secretion by reviewing the available literature.
基金This work has been supported by grants from the Taishan Scholars Program(TSQN201812015)the Program for Multidisciplinary Research and Innovation Team of Young Scholars at Shandong University(2020QNQT007).
文摘Objective:The aim of this study is to explore the active ingredients and mechanism of action of danhong injection(DHI)in treating myeloproliferative neoplasms using network pharmacology.Methods:The TCMSP platform and relevant literature were used to search for the active ingredients and targets of Radix Salviae and Carthami Flos in DHI.Disease targets related to myeloproliferative neoplasms were obtained from the GEO database,GeneCards,and DisGeNET database.The queried component targets were normalized using the UniProt database.Potential targets were identified by constructing protein-protein interactions networks using STRING 11.5 and visualized and analyzed using Cytoscape 3.9.1.GO and KEGG analysis were performed using the Metascape platform,and visualization was done using the built-in plug-in CluoGO or SangerBox platforms with Cytoscape 3.9.1.Results:The active ingredients of DHI for treating myeloproliferative neoplasms mainly consist of flavonoids and o-benzoquinones,including quercetin,luteolin,kaempferol,stigmasterol,tanshinone iia,cryptotanshinone,beta-carotene,2-isopropyl-8-methylphenanthrene-3,4-dione,and neocryptotanshinone ii.The potential targets are JUN,TP53,STAT3,AKT1,MAPK1,RELA,TNF,MAPK14,IL6,and FOS.The relevant signaling pathways involved are mainly TNFαsignaling pathway,PI3K-Akt signaling pathway,apoptosis,IL-17 signaling pathway,cellular senescence,MAPK signaling pathway,p53 signaling pathway,JAK-STAT signaling pathway,and NF-kappa B signaling.Conclusions:DHI acts mainly through flavonoids and o-benzoquinones to treat myeloproliferative neoplasms in a multi-targeted and multi-pathway manner.
基金Supported by Zhejiang Provincial Natural Science Foundation of China,No.LY14H310010Public Welfare Technology Applied Research Project of Zhejiang Province?Experimental Animal Science and Technology Project,No.2013C37020Key Project of Chinese Ministry of Education,No.212073
文摘Despite that some approved drugs and genetically engineered vaccines against hepatitis B virus(HBV)are available for HBV patients,HBV infection is still a severe public health problem in the world.All the approved therapeutic drugs(including interferonalpha and nucleoside analogues)have their limitations.No drugs or therapeutic methods can cure hepatitis B so far.Therefore,it is urgently needed to discover and develop new anti-HBV drugs,especially nonnucleoside agents.Naturally originated compounds with enormous molecular complexity and diversity offer a great opportunity to find novel anti-HBV lead compounds with specific antiviral mechanisms.In this review,the natural products against HBV are discussed according to their chemical classes such as terpenes,lignans,phenolic acids,polyphenols,lactones,alkaloids and flavonoids.Furthermore,novel mode of action or new targets of some representative anti-HBV natural products are also discussed.The aim of this review is to report new discoveries and updates pertaining to anti-HBV natural products in the last 20years,especially novel skeletons and mode of action.Although many natural products with various skeletons have been reported to exhibit potent anti-HBV effects to date,scarcely any of them are found in the list of conventional anti-HBV drugs worldwide.Additionly,in anti-HBV mechanism of action,only a few references reported new targets or novel mode of action of antiHBV natural products.
基金supported by grants from the National Natural Science Foundation of China (81770176)the special support plan for Zhejiang Province High-Level Talents (2019R52011)。
文摘The management of bacterial infections is becoming a major clinical challenge due to the rapid evolution of antibiotic resistant bacteria.As an excellent candidate to overcome antibiotic resistance,antimicrobial peptides(AMPs)that are produced from the synthetic and natural sources demonstrate a broad-spectrum antimicrobial activity with the high specificity and low toxicity.These peptides possess distinctive structures and functions by employing sophisticated mechanisms of action.This comprehensive review provides a broad overview of AMPs from the origin,structural characteristics,mechanisms of action,biological activities to clinical applications.We finally discuss the strategies to optimize and develop AMP-based treatment as the potential antimicrobial and anticancer therapeutics.
基金supported by National Institutes of Health grant AR066831-01ASBMR GAP grant to Weirong R Xingsupported by a senior research career scientist award from the Department of Veteran’s Affairs
文摘Leucine-rich repeat kinase 1 (LRRK1) plays a critical role in regulating cytoskeletal organization, osteoclast activity, and bone resorption with little effect on bone formation parameters. Deficiency of Lrrk1 in mice causes a severe osteopetrosis in the metaphysis of the long bones and vertebrae bones, which makes LRRK1 an attractive alternative drug target for the treatment of osteoporosis and other high-turnover bone diseases.This review summarizes recent advances on the functions of the Lrrk1-related family members, Lrrk1deficiency-induced skeletal phenotypes, LRRK1 structure–function, potential biological substrates and interacting proteins, and the mechanisms of LRRK1 action in osteoclasts.
文摘Nagilactones are tetracyclic natural products isolated from various Podocarpus species.These lactone-based compounds display a range of pharmacological effects,including antifungal,anti-atherosclerosis,anti-inflammatory and anticancer activities reviewed here.The most active derivatives,such as nagilactones C,E and F,exhibit potent anticancer activities against different cancer cell lines and tumor models.A comprehensive analysis of their mechanism of action indicates that their anticancer activity mainly derives from three complementary action:(i)a drug-induced inhibition of cell proliferation coupled with a cell cycle perturbation and induction of apoptosis,(ii)a blockade of the epithelial to mesenchymal cell transi-tion contributing to an inhibition of cancer cell migration and invasion and(iii)a capacity to modulate the PD-L1 immune checkpoint.Different molecular effectors have been implicated in the antitumor activity,chiefly the AP-1 pathway blocked upon activation of the JNK/c-Jun axis.Nag-C is a potent inhibitor of protein synthesis binding to eukaryotic ribosomes and inhibition of different protein kinases,such as RIOK2 and JAK2,has been postulated with Nag-E.The literature survey on nagilactones highlights the therapeutic potential of these little-known terpenoids.The mechanistic analysis also provides useful information for structurally related compounds(podolactones,oidiolactones,inumakilactones)isolated from Podo-carpus plants.
基金This research did not receive any specific grant from funding agencies in the public,commercial,or not-for-profit sectors。
文摘Biflavonoids are divided in two classes:C-C type compounds represented by the dimeric compound amentoflavone and C-O-C-type compounds typified by hinokiflavone(HNK)with an ether linkage between the two connected apigenin units.This later sub-group of bisflavonyl ethers includes HNK,ochnaflavone,delicaflavone and a few other dimeric compounds,found in a variety of plants,notably Selaginella species.A comprehensive review of the anticancer properties and mechanism of action of HNK is provided,to highlight the anti-proliferative and anti-metastatic activities of HNK and derivatives,and HNK-containing plant extracts.The anticancer effects rely on the capacity of HNK to interfere with the ERK1-2/p38/NFκB signaling pathway and the regulation of the expression of the matrix metalloproteinases MMP-2 and MMP-9(with a potential direct binding to MMP-9).In addition,HNK was found to function as a potent modulator of pre-mRNA splicing,inhibit-ing the SUMO-specific protease SENP1.As such,HNK represents a rare SENP1 inhibitor of natural origin and a scaffold to design synthetic compounds.Oral formulations of HNK have been elaborated to enhance its solubility,to facilitate the compound delivery and to enhance its anticancer efficacy.The review shed light on the anticancer potential of C-O-C-type biflavonoids and specifically on the pharmacological profile of HNK.This compound deserves further attention as a regu-lator of pre-mRNA splicing,useful to treat cancers(in particular hepatocellular carcinoma)and other human pathologies.
基金supported by Innovative Talent Promotion Plan-Key Technology Innovation Team Plan(2017KCT-27).
文摘Objective:To predict the mechanism of action of San Huang lotion for topical treatment of eczema at the level of network pharmacology and molecular docking technology.Methods:The active ingredients and corresponding targets of San Huang lotion were collected using the TCMSP data platform and UniProt;the relevant gene targets of San Huang lotion were collected using the GeneCards database,OMIM database,TTD database,and DrugBank database;the intersection targets of San Huang lotion and eczema were obtained by creating avenn diagram;the key active ingredients and targets were screened by constructing a disease-active ingredient-target map,and the key active ingredients and core targets were screened out by constructing disease-active ingredient-target diagrams and PPInetwork diagrams;GOand KEGGenrichment analyses were conducted using the metascapewebsite and the higher significant entries were selected to produce bar charts and bubble plots.Finally,molecular docking of key active ingredients and core targets was performed.Results:A total of 134 active ingredients and 3,320 eczema-related target genes were screened for San Huang lotion,and 126 intersecting targets were obtained for San Huang lotion and eczema.The five key active ingredients of San Huang lotion for topical treatment of eczema and six core targets ofAKT1,TNF,IL6,IL1B,TP53andVEGFA were obtained by drug-active ingredient-target map and PPInetwork map.The GOand KEGGenrichment analysis showed that the topical treatment of eczema withSanHuanglotion might be mediated throughIL-17signaling pathway,TNFsignaling pathway and Th17cell differentiation pathway.The molecular docking results showed that the docking binding energy of key active ingredients and core targets was mostly less than-5 kcal/mol,and the docking was good.Conclusion:The quercetin,luteolin,wogonin,formononetin,beta-sitosterol and other active ingredients in San Huang lotion may act on eczema through AKT1,TNF,IL6,IL1B,TP53,VEGFA and other targets,and through IL-17signaling pathway,TNFsignaling pathway,Th17cell differentiation and other pathways.
基金supported by the system issue of Key Laboratory of Guangxi Basic Chinese Medicine Research(Grant No.16-380-58-06)
文摘Objective:To explore the protective effect and possible mechanism of action of Zhuyu Annao pill in mice with intracerebral hemorrhage(ICH).Methods:Sixty mice were divided into the control group,hemorrhage group,drug-treated group(after hemorrhage),TLR4-knockout hemorrhage group and TLR4-knockout hemorrhage + drug-treated group(after hemorrhage) with 12 in each group.Model of autologous ICH was established in all groups.After drilling and 12 h of fasting,models in the control group hemorrhage group and TLR4-knockout hemorrhage group were all drenched with 10 mL/kg distilled water by intragastric administration.Models in the drug-treated group and TLR4-knockout hemorrhage + drugtreated group were drenched with 6.25 g/kg of Zhuyu Annao pill.All groups were treated for 7 d.Longa scoring method was used to measure the neurological defect scores and determine the brain water contents of all groups;ELISA was employed to detect the inflammatory factor interleukin(IL)-6,tumor necrosis factor- α(TNF- α) and IL-1β in brain tissues;and Western blot was applied to test the expression quantities of apoptotic protein Bax and anti-apoptotic protein Bcl-2 in brain tissues.Results:At day 3 and7,compared with the hemorrhage group,the neurological defect scores of the drug-treated group,TLR4-knockout hemorrhage group and TLR4-knockout hemorrhage + drug-treated group decreased significantly(P<0.05) Compared with the hemorrhage group,the brain water contents of the drug-treated group,TLR4-knockout hemorrhage group and TLR4-knockout hemorrhage + drug-treated group reduced significantly(P<0.05) Compared with the hemorrhage group,the inflammatory factor IL-6,TNF-α and IL-1β of the drug-treated group,TLR4-knockout hemorrhage group and TLR4-knockout hemorrhage + drug-treated group decreased significantly(P<0.05).Compared with the hemorrhage group,the expression of apoptotic protein Bax of the drug-treated group,TLR4-knockout hemorrhage group and TLR4-knockout hemorrhage+ drug-treated group decreased significantly and the expression of anti-apoptotic protein Bcl-2 increased significantly(P<0.05).Conclusions:Zhuyu Annao pill can alleviateencephaledema for mice with ICH and reduce inflammatory responsesandnerve cell apoptosis.TLR4 can mediate inflammatory injury induced by ICH.Thus,Zhuyu Annao pill can play a protective role for brains by decreasing the expression of TLR4.
基金supported by the ‘13th Five-Year’ scientific research and innovation team of Tianjin University of Science&Technology(green food packaging and intelligent packaging)the ‘12th Five-Year’ National Science and Technology Support Project of People's Republic of China(Grant No.2015BAD16B05-02)
文摘Objective: To find a natural plant essential oil(EO) with excellent antimicrobial effect on food-borne bacteria and to explore the mechanism of its antimicrobial function against Escherichia coli(E. coli). Methods: The antimicrobial activity of seven EOs against Gramnegative E. coli ATCC 8739 and Gram-positive Staphylococcus aureus ATCC 6538 was investigated using agar disk diffusion method, and the minimum inhibitory concentration(MIC) and minimum bactericidal concentration(MBC) of each EO was determined using the broth dilution method. The chemical composition of the Trachyspermum copticum(T. copticum) EO was analyzed using gas chromatography–mass spectrometry(GC/MS). In order to explore the mechanism of the antimicrobial action, 1 MIC and 2 MIC of T. copticum EO was added to a suspension of E. coli, the growth curve and the scanning electron microscopy(SEM) analysis of E. coli, and the release of cell constituents and protein and potassium ions from the bacterial cell were measured. Results: The T. copticum EO had the best antimicrobial activity against the test bacteria, and 10 compounds accounting for 94.57% of the total oil were identified, with the major components being thymol(46.22%), p-cymene(19.03%), and 毭-terpinene(22.41%). The addition of 1 MIC T. copticum EO significantly inhibited the growth of E. coliand increased the release of cell constituents and protein and potassium ions from the bacterial cells. Scanning electron micrographs showed that T. copticum EO caused most of the E. colicell membranes to collapse and rupture, leading to cell death. Conclusions: These results indicate that T. copticum EO is a good natural antimicrobial agent for food-borne pathogens.
基金Supported by Applied Basic Research Project of Yunnan Province(2017FD087)National Natural Science Foundation of China(31660559)
文摘This study was conducted to comprehensively evaluate the effects of salicylic acid and sodium molybdate on cold tolerance of an ornamental plant Bougainvillea glabra and to provide a theoretical guidance for landscape maintenance.B.glabra plants were treated with 0.5 mmol/L salicylic acid and 2.0 μmol/L alone or in combination,and then exposed to low temperature stress before physiological indices were measured.The results showed that all salicylic acid and sodium molybdate treatments reduced the relative conductivity and malondialdehyde( MDA) content of B.glabra to varying extents under the stress of low temperature,and more significant effect was achieved by using the two agents in combination.Oxygen free radicals production rate increased with decreasing temperature from 20 to 6 ℃,but declined with temperature decreasing from 3 to-3 ℃.The SOD activity of the control( CK) was significantly lower than that of other treatments at 0 and-3 ℃.The treatments with salicylic acid and sodium molybdate alone and in combination increased POD activity of B.glabra plants,especially at 0 ℃,as the POD activity of treatments T1,T2 and T3 was significantly higher than that of CK at 0 ℃.In addition,under low temperature stress,the contents of soluble sugar,starch and proline increased initially and decreased subsequently with temperature decreasing.The soluble sugar content at 3 ℃,starch and proline contents at 0 and-3 ℃ in treatments with salicylic acid and sodium molybdate alone and in combination were significantly higher than those of CK.All above results proved that salicylic acid and sodium molybdate are able to improve cold tolerance of B.glabra,and better effect can be achieved by using them together.
文摘Life expectancy in industrialized and developed countries will continue to increase in the near future. Consequently, over the last years, the incidence and social impact of neurodegenerative diseases have increased, highlighting an urgent need for new and more effective therapeutic strategies to counter these terrible disorders. While we tend to think about neurodegenerative diseases as conditions that are uniquely associated with the elder age, these diseases cover a diverse range across the entire lifespan, even affecting infants and children.
基金the Natural Science Foundation of China(81373985).
文摘Objective:To predict the potential active ingredients (PAIs) and mechanism of action of traditional Chinese medicine formulations used to delay aging.Methods:We incorporated the use of quantum-chemistry calculations and machine learning to predict the active ingredients of some Chinese herbal medicines used to delay aging.Then,a network-pharmacology approach was used to uncover how these PAls delayed aging.Results:Twelve PAls with anti-aging effects were discovered:androsterone,MHP,cortisone,propyl methyl trisulfide,retinol,retinal,cortisol,11-cis-Retinol (2R,3R)-3-hydroxyproline,4,5alpha-Dihydrocortisone (2S)-2-ammonio-6-ureidohexanoate and17alpha,21-Dihydroxy-5beta-pregnane-3,11,20-trione.Enrichment analyses indicated that a putative compound target and aging target were significantly associated with:regulation of the immune system;insulin receptor signaling pathway;regulation of the mitotic cell cycle;response to nutrient levels;response to oxidative stress;release of cytochrome c from mitochondria;learning or memory;inflammatory response.Conclusions:A novel method was proposed to predict the PAls of anti-aging herbal medicines by incorporating quantum-chemistry calculations and machine learning.Then,a network-pharmacology approach was used to uncover how these PAls delay aging.The information provided by our study on PAls may aid the discovery of anti-aging drugs.
文摘Background: Recently, high efficacy of the chemotherapeutic regimen combining clarithromycin (CAM) with lenalidomide (Len) and dexamethasone (Dex) (BiRD) in treating multiple myeloma (MM) patients has been reported. However, the exact mechanism of added CAM has not been fully elucidated. This case report will provide helpful information for understanding the significance and the mechanism of action of CAM as an add-on therapy. Patient: A 78-year-old female patient with IgA-λ type MM was treated with low-dose Len coupled with low-dose Dex (low Rd), and excellent response was achieved for long term, but she later became refractory to this treatment. Then, CAM was added to low Rd (low Rd-CAM, i.e., modified BiRD therapy). This add-on-therapy was found to be effective, but later suspended because of pneumonitis. Then, low-dose Len coupled with CAM (low R-CAM) treatment was applied;but effect of this Dex-free treatment was insufficient. Thus, low Rd-CAM was reapplied and satisfactory reduction of IgA was achieved. This fact suggests that low Rd-CAM is the favorable combination, Dex is requisite and CAM might have enhanced the effect of Dex. In this case, various serum cytokines were examined during the course of illness. Only interleukin-6 showed apparent increase, and tumor necrosis factor-α, transforming growth factor-β, soluble IL-2 receptors and C-reactive protein showed the slight increase during low Rd-CAM treatment. The results seem somewhat conflicting, but it seems that intricate cytokine response due to immune activation might have occurred during low Rd-CAM treatment.
文摘Plants from the genus Cannabis,and strains of Cannabis sativa in particular,have been used in medicine since ancient times.The Cannabis plant contains more than 500 chemical compounds,with two main phytocannabinoids consisting of Δ9-tetrahydrocannabinol(THC),the psychoactive constituent,and cannabidiol(CBD),which does not bear this effect.This paper aims at providing a perspective on the potential therapeutic effects of CBD based on its preferential interaction with transient potential receptor V2(TRPV2).Many formulations based on Cannabis extract have been licensed for therapeutic use in some Western countries.Among these,the most relevant are Sativex(THC+CBD,used mainly for the treatment of spasticity in multiple sclerosis)and Epidyolex(purified plant-derived CBD,used for some rare childhood epilepsies).
