Background:Qingyangshen(Cynanchum otophyllum C.K.Schneid)is a folk drug for treating depression and other mental disorders induced by social defeat stress.Neuroplasticity in the hippocampus is essential for the modula...Background:Qingyangshen(Cynanchum otophyllum C.K.Schneid)is a folk drug for treating depression and other mental disorders induced by social defeat stress.Neuroplasticity in the hippocampus is essential for the modulation of cognition and emotion,and its impairment may contribute to the development and progression of depression.Our previous studies have found that Qingyangshen glycosides(QYS)can improve depression-like behavior in social failure mouse models,mainly through PGC-1α/FNDC5/BDNF signaling pathways activation,but its effects and mechanisms on hippocampal neuroplasticity remain unknown.Methods:Chronic social defeat stress(CSDS)was used to induce social defeat in mice.Morphological changes in the hippocampus were observed by H&E staining and Golgi staining.Immunofluorescence double staining was used to detect the expression of synaptophysin(SYN)and postsynaptic density protein-95(PSD-95),while western blot was employed to evaluate PSD-95,SYN,and doublecortin(DCX)proteins.The pathological processing of social defeat and the therapeutic effects of QYS on it was confirmed through behavioral assessment associated with morpho-logic observation.Results:During the whole study,the sucrose preference indices and OFT activity time of CSDS mice were significantly decreased(p≤0.05),and the tail suspension immobil-ity time was significantly increased(p≤0.05),suggesting that the mice had significant depressive symptoms.Treatment with QYS(25,50,and 100 mg/kg)significantly al-leviated depressive symptoms in CSDS mice,which was demonstrated by significantly(p≤0.05 or p≤0.01)reducing the duration of tail-hanging immobility and increasing the tendency of sucrose preference indices and OFT activity time.QYS treatment also significantly increased the expression of DCX,PSD-95,and SYN proteins,which play a crucial role in depression.Conclusions:QYS alleviated these symptoms by enhancing hippocampal neuroplasti-city through upregulating the expression of synapse-associated proteins(SAPs).The therapeutic mechanism of QYS may involve modulating the neuroplasticity of hip-pocampus neurons by altering the expression of SAPs.展开更多
Polyphenols,a diverse group of naturally occurring compounds found in plants,have garnered significant attention for their potential therapeutic properties in treating neurodegenerative diseases(NDs).The Wnt/β-cateni...Polyphenols,a diverse group of naturally occurring compounds found in plants,have garnered significant attention for their potential therapeutic properties in treating neurodegenerative diseases(NDs).The Wnt/β-catenin(WβC)signaling pathway,a crucial player in neurogenesis,neuronal survival,and synaptic plasticity,is involved in several cellular mechanisms related to NDs.Dysregulation of this pathway is a hallmark in the development of various NDs.This study explores multiple polyphenolic compounds,such as flavonoids,stilbenes,lignans,and phenolic acids,and their potential to protect the nervous system.It provides a comprehensive analysis of their effects on the WβC pathway,elucidating their modes of action.The study highlights the dual function of polyphenols in regulating and protecting the nervous system,providing reassurance about the research benefits.This review provides a comprehensive analysis of the results obtained from both in vitro studies and in vivo research,shedding light on how these substances influence the various components of the pathway.The focus is mainly on the molecular mechanisms that allow polyphenols to reduce oxidative stress,inflammation,and apoptotic processes,ultimately improving the function and survival of neurons.This study aims to offer a thorough understanding of the potential of polyphenols in targeting the WβC signaling pathway,which could lead to the development of innovative therapeutic options for NDs.展开更多
Objective:To isolate and identify active constituents from Gracilaria chorda extract prepared under subcritical water conditions at 210℃(GCSW210)and evaluate their anti-obesity and anti-diabetic effects in 3T3-L1 adi...Objective:To isolate and identify active constituents from Gracilaria chorda extract prepared under subcritical water conditions at 210℃(GCSW210)and evaluate their anti-obesity and anti-diabetic effects in 3T3-L1 adipocytes and high-fat diet(HFD)-induced obese zebrafish larvae.Methods:GCSW210 was fractionated through solvent partitioning,ion-exchange chromatography,and silica gel medium-pressure liquid chromatography,followed by preparative high performance liquid chromatography.At each step,bioactivities were assessed in 3T3-L1 adipocytes by Oil Red O staining and 2-NBDG uptake assays.The most active fractions were further purified,and isolated compounds were tested in HFD-induced obese zebrafish larvae.Results:Liquid chromatography-hyphenated analysis with reference standards identified two major compounds in GCSW210:5-hydroxymethylfurfural and bis(5-formylfurfuryl)ether.Both compounds significantly inhibited lipid accumulation in 3T3-L1 adipocytes and modulated gene expression associated with adipogenesis,glucose metabolism,and inflammation in zebrafish.They also enhanced glucose uptake,reduced circulating glucose levels,and improved insulin sensitivity.Notably,the effects were comparable to those of the crude GCSW210 extract.In silico docking studies confirmed stable interactions of both compounds with key metabolic and inflammatory targets,with bis(5-formylfurfuryl)ether showing stronger binding affinities.Conclusions:These findings suggest that 5-hydroxymethylfurfural and bis(5-formylfurfuryl)ether are key contributors to the therapeutic activity of Gracilaria chorda,highlighting its potential as a functional food ingredient for the prevention or management of metabolic disorders.展开更多
Traditional Chinese herbal drugs have been used for thousands of years in Chinese pharmacopoeia. The bark of Magnolia officinalis Rehder ＆ E. Wilson, known under the pinyin name ＂Houpo＂, has been traditionally used...Traditional Chinese herbal drugs have been used for thousands of years in Chinese pharmacopoeia. The bark of Magnolia officinalis Rehder ＆ E. Wilson, known under the pinyin name ＂Houpo＂, has been traditionally used in Chinese and Japanese medicines for the treatment of anxiety, asthma, depression, gastrointestinal disorders, headache, and more. Moreover, Magnolia bark extract is a major constituent of currently marketed dietary supplements and cosmetic products. Much pharmacological activity has been reported for this herb and its major compounds notably antioxidant, anti-inflammatory, antibiotic and antispasmodic effects. However, the mechanisms underlying this have not been elucidated and only a very few clinical trials have been published. In vitro and in vivo toxicity studies have also been published and indicate some intriguing features. The present review aims to summarize the literature on M. officinalis bark composition, utilisation, pharmacology, and safety.展开更多
Breast cancer is the most common cancer among women. In recent years, many in vitro and in vivo studies indicate that green tea possesses anti-cancer effects. The epidemiological studies, however, have produced inconc...Breast cancer is the most common cancer among women. In recent years, many in vitro and in vivo studies indicate that green tea possesses anti-cancer effects. The epidemiological studies, however, have produced inconclusive results in humans. Likewise, results from animal models about the preventive or therapeutic effects of green tea components are inconclusive. The mechanisms by which green tea intake may influence the risk of breast cancer in humans remain elusive. Here, we review recent studies of green tea polyphenols and their applications in the prevention and treatment of breast cancer. Furthermore, we discuss the effect of green tea components on breast cancer by reviewing epidemiological studies, animal model studies and clinical trials. At last, we discuss the mechanisms by which green tea components suppress the develop-ment and recurrence of breast cancer. A better understanding of the mechanisms will improve the utilization of green tea in breast cancer prevention and therapy and pave the way to novel prevention and treatment strategies for breast cancer.展开更多
India has a great wealth of various naturally occurring plant drugs which have great potential pharmacological activities.Datura stramonium(D.stramonium is one of the widely well known folklore medicinal herbs.The tro...India has a great wealth of various naturally occurring plant drugs which have great potential pharmacological activities.Datura stramonium(D.stramonium is one of the widely well known folklore medicinal herbs.The troublesome weed,D.stramonium is a plant with both poisonous and medicinal preperties and has been proven to have great pharmacological potential with a great utility real usage in folklore medicine.D.stromonium has been scientifically proven to contain alkaloids,tannins,carbohydrates and proteins.This plant has contributed various pharmacological actions in the scientific field of Indian systems of medicines like analgesic and antiasthmatic activities.The present paper presents an exclusive review work on the ethnomedical,phytochemical,pharmacological activities of this plant.展开更多
Metabolic engineering of the tumor microenvironment has emerged as a new strategy.Lactate dehydrogenase A(LDHA)is a prominent target for metabolic engineering.Here,we designed a cationic lipid nanoparticle formulation...Metabolic engineering of the tumor microenvironment has emerged as a new strategy.Lactate dehydrogenase A(LDHA)is a prominent target for metabolic engineering.Here,we designed a cationic lipid nanoparticle formulation for LDHA gene editing.The plasmid DNA delivery efficiency of our lipid nanoparticle formulations was screened by testing the fluorescence of lipid nanoparticles complexed to plasmid DNA encoding green fluorescence protein(GFP).The delivery efficiency was affected by the ratios of three components:a cationic lipid,cholesterol or its derivative,and a fusogenic lipid.The lipid nanoparticle designated formulation F3 was complexed to plasmid DNA co-encoding CRISPR-associated protein 9 and LDHA-specific sgRNA,yielding the lipoplex,pCas9-sgLDHA/F3.The lipoplex including GFP-encoding plasmid DNA provided gene editing in HeLa-GFP cells.Treatment of B16F10 tumor cells with pCas9-sgLDHA/F3 yielded editing of the LDHA gene and increased the pH of the culture medium.pCas9-sgLDHA/F3 treatment activated the interferon-gamma and granzyme production of T cells in culture.In vivo,combining pCas9-sgLDHA/F3 with immune checkpoint-inhibiting anti-PD-L1 antibody provided a synergistic antitumor effect and prolonged the survival of tumor model mice.This study suggests that combining metabolic engineering of the tumor microenvironment with immune checkpoint inhibition could be a valuable antitumor strategy.展开更多
Here, we report that the modification of liposome surfaces with AG73 peptides enhances delivery of the lipophilic anticancer drug, edelfosine, to tumor cells overexpressing the cellsurface receptor, syndecan 2. To tes...Here, we report that the modification of liposome surfaces with AG73 peptides enhances delivery of the lipophilic anticancer drug, edelfosine, to tumor cells overexpressing the cellsurface receptor, syndecan 2. To test the effect of liposomal surface density of AG73 peptides on cellular uptake, we synthesized AG73 peptide-conjugated polyethylene glycol(MW 2000)lipid and incorporated it into fluorescence dye-labeled anionic liposomes with different ligand densities(1, 2, or 5 mol% of total lipids). Cellular uptake of AG73-peptide–modified liposomes gradually increased in proportion to the surface ligand density. The percentages of cells positive for AG73-modified, fluorescent-dye–labeled liposomes were 19.8 ± 2.0%, 23.1 ± 5.0%,and 99.2 ± 1.0%, for ligand mole percentages of 1, 2, and 5, respectively. The cell-targeting ability of AG73-modified liposomes was not significantly altered by the serum content of culture media. In keeping with the observed enhanced cellular uptake, AG73-peptide–modified liposomes entrapping edelfosine exhibited greater cancer cell-killing effects compared with unmodified liposomes. Following intravenous administration into tumor-bearing mice,AG73-peptide–modified liposomes showed 2.1-fold greater accumulation in tumors than unmodified liposomes. These results support the feasibility of using syndecan 2–directed liposomes for delivery of edelfosine.展开更多
Although current anticancer immunotherapies using immune checkpoint inhibitors(ICIs)have been reported with a high clinical success rate,numerous patients still bear‘cold’tumors with insufficient T cell infiltration...Although current anticancer immunotherapies using immune checkpoint inhibitors(ICIs)have been reported with a high clinical success rate,numerous patients still bear‘cold’tumors with insufficient T cell infiltration and low immunogenicity,responding poorly to ICI therapy.Considering the advancements in precision medicine,in-depth mechanism studies on the tumor immune microenvironment(TIME)among cold tumors are required to improve the treatment for these patients.Nanomedicine has emerged as a promising drug delivery system in anticancer immunotherapy,activates immune function,modulates the TIME,and has been applied in combination with other anticancer therapeutic strategies.This review initially summarizes the mechanisms underlying immunosuppressive TIME in cold tumors and addresses the recent advancements in nanotechnology for cold TIME reversal-based therapies,as well as a brief talk about the feasibility of clinical translation.展开更多
We report the activation of anticancer effector functions of T cells through nanoparticle-induced lipid metabolic reprogramming.Fenofibrate was encapsulated in amphiphilic polygamma glutamic acid-based nanoparticles(F...We report the activation of anticancer effector functions of T cells through nanoparticle-induced lipid metabolic reprogramming.Fenofibrate was encapsulated in amphiphilic polygamma glutamic acid-based nanoparticles(F/ANs),and the surfaces of F/ANs were modified with an anti-CD3e f(ab′)2 fragment,yielding aCD3/F/ANs.An in vitro study reveals enhanced delivery of aCD3/F/ANs to T cells compared with plain F/ANs.aCD3/F/AN-treated T cells exhibited clear mitochondrial cristae,a higher membrane potential,and a greater mitochondrial oxygen consumption rate under glucose-deficient conditions compared with T cells treated with other nanoparticle preparations.Peroxisome proliferatoractivated receptor-αand downstream fatty acid metabolismrelated genes are expressed to a greater extent in aCD3/F/AN-treated T cells.Activation of fatty acid metabolism by aCD3/F/ANs supports the proliferation of T cells in a glucose-deficient environment mimicking the tumor microenvironment.Real-time video recordings show that aCD3/F/AN-treated T cells exerted an effector killing effect against B16F10 melanoma cells.In vivo administration of aCD3/F/ANs can increase infiltration of T cells into tumor tissues.The treatment of tumor-bearing mice with aCD3/F/ANs enhances production of various cytokines in tumor tissues and prevented tumor growth.Our findings suggest the potential of nanotechnology-enabled reprogramming of lipid metabolism in T cells as a new modality of immunometabolic therapy.展开更多
Purpose: This study was conducted to audit prophylactic antibiotic use and to quantify the rate of wound infection. Methods: Across-sectional prospective study was conducted in the Obstetrics and Gynecology Department...Purpose: This study was conducted to audit prophylactic antibiotic use and to quantify the rate of wound infection. Methods: Across-sectional prospective study was conducted in the Obstetrics and Gynecology Department in Khartoum Teaching Hospital, Sudan during March 1st to 31st October 2010. All Patients (aged >18 years) were included. Results: Overall 725 patients were included. The performed surgical procedures were 751;of these 578 (76.9%) were Caesarean sections. Overall rate of wound infection was 7.8%. The rate of wound infection among patients operated on for caesarean section and abdominal hysterectomy was 8.3%, and 9.2%, respectively. Multivariate logistic analysis showed that body mass index [BMI] ≥ 30 kg/m2 OR 2.1, 95% CI (1.1 - 4.0), (P = 0.019) was the major independent risk factor for occurrence of wound infection. Evaluation of prescriptions’ parameters against the stated criteria showed that 113 (15.8%) patients were given antibiotics with adequate spectrum of activity, 611 (85.3%) given sub-dose/s, 83 (11.6%) received the first preoperative dose/s in a proper time window, and 716 (100%) had prophylaxis for extended duration. Overall conformity to the stated criteria for the evaluation of prescription’s parameters was not achieved in all prescriptions. Conclusions: In this setting, antibiotics were irrationally used and wound infection rate was high, and the situation calls for multiple interventions to correct the situation, through the activation of the infection control committee in the hospital and development of antimicrobial subcommittee to develop policies for the use and auditing of prophylactic antibiotics.展开更多
Obesity is often identified as a nutritional disorder, and this condition continues to be one of the most important yet preventable health hazards. It may be a complex group of diseases and should be characterized as ...Obesity is often identified as a nutritional disorder, and this condition continues to be one of the most important yet preventable health hazards. It may be a complex group of diseases and should be characterized as a syndrome that results from an imbalance between energy intake and expenditure. Furthermore, obesity is associated with several diseases such as diabetes mellitus, atherosclerosis, cardiovascular diseases, osteoarthritis, and hypertension. In previous studies, we found that in Asia, especially in the Asean region, carbohydrates are heavily represented in the diet. Therefore, we used a high carbohydrate diet to induce obesity in rats. The aim of this study was to evaluate the potency of Tamarindus indica pulp as an anti-obesity agent in a high carbohydrate diet animal model. The antiobesity effect was evaluated in this in vivo model at doses of 75 mg/kg·bw and 225 mg/kg·bw. Treatment was started in week 3 and week 9, and biochemical characteristics were measured every 3 weeks. In the end of the study period, insulin resistance and adiponectin levels were measured. TIWE(Tamarindus indica water extract) at a dose of 75 mg/kg·bw showed better efficacy than at a dose of 225 mg/kg·bw, and treatment started on week 3 was better than treatment started on week 9. TIWE has an anti-obesity effect associated insulin resistance by increasing adiponectin levels and insulin sensitivity, which can impact body weight, triglyceride levels, blood glucose levels, and body fat.展开更多
OBJECTIVE： The roots of Chlorophytum borivilanum are used in traditional medicine for the treatment of arthritis and inflammation. The aim of the work was to evaluate the anti-inflammatory activity of isolated saponi...OBJECTIVE： The roots of Chlorophytum borivilanum are used in traditional medicine for the treatment of arthritis and inflammation. The aim of the work was to evaluate the anti-inflammatory activity of isolated saponins from Chlorophytum borivilianum （ISCB）. METHODS： The ISCB was screened using the carrageenan-induced paw edema, histamine-induced paw edema, cotton pellet-induced granuloma, and Freund＇s adjuvant-induced arthritis in rats at orally administered doses of 3, 10, and 30 mg/kg. Effect of ISCB on histone deacetylase （HDAC） level was measured by the HDAC assay at the highest dose （30 mg/kg）. RESULTS： The results showed that the ISCB significantly reduced carrageenan-induced inflammation, histamine-induced inflammation, cotton pellet-induced granuloma and Freund＇s adjuvant-induced arthritis in rats. The ISCB at a dose of 30 mg/kg significantly inhibited HDAC level in rat paw tissue. CONCLUSION： It is concluded that saponins isolated from roots of C. borivilianum possess anti- inflammatory and anti-arthritic properties. ISCB may act by inhibiting histamine, prostaglandin and HDAC. This suggests that ISCBs have potential for therapeutic use in the treatment of inflammation and arthritis展开更多
Despite the progress of conventional vaccines,improvements are clearly required due to concerns about the weak immunogenicity of these vaccines,intrinsic instability in vivo,toxicity,and the need for multiple administ...Despite the progress of conventional vaccines,improvements are clearly required due to concerns about the weak immunogenicity of these vaccines,intrinsic instability in vivo,toxicity,and the need for multiple administrations.To overcome such problems,nanotechnology platforms have recently been incorporated into vaccine development.Nanocarrier-based delivery systems offer an opportunity to enhance the humoral and cellular immune responses.This advantage is attributable to the nanoscale particle size,which facilitates uptake by phagocytic cells,the gut-associated lymphoid tissue,and the mucosa-associated lymphoid tissue,leading to efficient antigen recognition and presentation.Modifying the surfaces of nanocarriers with a variety of targeting moieties permits the delivery of antigens to specific cell surface receptors,thereby stimulating specific and selective immune responses.In this review,we introduce recent advances in nanocarrierbased vaccine delivery systems,with a focus on the types of carriers,including liposomes,emulsions,polymer-based particles,and carbon-based nanomaterials.We describe the remaining challenges and possible breakthroughs,including the development of needlefree nanotechnologies and a fundamental understanding of the in vivo behavior and stability of the nanocarriers in nanotechnology-based delivery systems.展开更多
Nowadays,with the expanding enrollment of medical schools in our country,the competitive pressures of employment increase.It is very difficult for the graduates of these schools to find ideal jobs,but medical students...Nowadays,with the expanding enrollment of medical schools in our country,the competitive pressures of employment increase.It is very difficult for the graduates of these schools to find ideal jobs,but medical students with master or doctor degrees are relatively optimistic to the employment situation.As a result,more and more fresh medical graduates pursue the post-graduate education,thus forms a"rush of taking test of postgraduate"phenomenon[1].Clinical students展开更多
Considering the fact that liver is one of the most important organs in our body,it deserves special attention and protection.Among various recommended supplements,complementary and alternative medicines particularly h...Considering the fact that liver is one of the most important organs in our body,it deserves special attention and protection.Among various recommended supplements,complementary and alternative medicines particularly herbal remedies have received much attention owing to their truly healing properties.This review profits from Iranian traditional medicine and presents advantageous herbal guide directions for liver protection.According to credible Iranian medical literature such as Al Qanun Fil Tibb.Al-Havi and Makhzan-al-Aadvia.a wide spectrum of plants have been found to be useful for cleansing and protecting the liver.Some herbs such as ghafes(Agrimonia eupatoria),kasni(Cichorium intybus),anar(Punica granatum),darchin(Cinnamomum zeylanicum),za'feran(Crocus sativus),gole-sorkh(Rosa damascena) and zereshk(Berberis vulgaris) appeared to get strong consideration and were well documented as outstanding liver tonics.We conducted a comprehensive review of available Iranian medical resources such as scientific information database and medical sciences databases which cover all in vitro and in vivo studies of medicinal plants as liver tonics and hepatoprotcctive candidates.Literature survey was accomplished using multiple databases including PubMed,ISI web of knowledge,and Google Scholar.展开更多
Strategies for CADD vary depending on the extent of structural and other information available regarding the target (enzyme/receptor) and the ligands. Computer-aided drug design (CADD) is an exciting and diverse disci...Strategies for CADD vary depending on the extent of structural and other information available regarding the target (enzyme/receptor) and the ligands. Computer-aided drug design (CADD) is an exciting and diverse discipline where various aspects of applied and basic research merge and stimulate each other. In the early stage of a drug discovery process, researchers may be faced with little or no structure activity relationship (SAR) information. The process by which a new drug is brought to market stage is referred to by a number of names most commonly as the development chain or “pipeline” and consists of a number of distinct stages. To design a rational drug, we must firstly find out which proteins can be the drug targets in pathogenesis. In present review we reported a brief history of CADD, DNA as target, receptor theory, structure optimization, structure-based drug design, virtual high-throughput screening (vHTS), graph machines.展开更多
Background Influenza vaccination has been clinically shown to reduce adverse cardiovascular outcomes in acute coronary syndrome （ACS） patients, but the economic perspectives can provide important data to make inform...Background Influenza vaccination has been clinically shown to reduce adverse cardiovascular outcomes in acute coronary syndrome （ACS） patients, but the economic perspectives can provide important data to make informed decisions. This study aimed to perform the economic evaluation of lifelong annual influenza vaccination for cardiovascular events and well-established pneumonia prevention. Methods Lifetime costs, life-expectancy, and quality-adjusted live years （QALYs） were estimated beyond one-year cycle length of a six-health states Markov model condition on whether a hospitalization for ACS, stroke, heart failure, pneumonia, no hospitalizations occurred, or death. The comparison of three age-groups of 40-49, 50-65, and 〉 65 years scenario was performed. Incremental cost-effectiveness ratio （ICER） and net monetary benefit （NMB） were presented as a societal perspective in 2016. The model robustness was determined by one-way and prob- abilistic sensitivity analyses. Results The influenza vaccination was cost-effective in all age-groups, by dominant ICERs （lower cost with higher effectiveness） which was completely lower than acceptable willingness-to-pay threshold of Thailand [160,000 THB （4,466.8 USD） per QALYs], with a great incremental value of NMB. Especially, the 50-year-old-and- above scenario was shown as the most benefit at 129,092 THB （3,603.9 USD） for each patient. Conclusions The annually additional influenza vaccination to standard treatment in ACS was cost-effective in all age-groups, which should be considered in clinical practice and health-policy making process.展开更多
基金Guizhou Administration of TCM,Traditional Chinese medicine,Ethnic Medicine Science and Technology Research Special Project,Grant/Award Number:QZYY-2022-008Subsidy Fund for Scientific Research and Innovation Exploration Project,National Natural Science Foundation of China of Guizhou University of Traditional Chinese Medicine,Grant/Award Number:2018YFC170810502+1 种基金Science and Technology Fund Project of Guizhou Provincial Health Commission,Grant/Award Number:gzwkj2023-147Development of animal models for drug discovery-brain diseases.National Research and Development Project of China,MOST,Grant/Award Number:2023YFF0724802.
文摘Background:Qingyangshen(Cynanchum otophyllum C.K.Schneid)is a folk drug for treating depression and other mental disorders induced by social defeat stress.Neuroplasticity in the hippocampus is essential for the modulation of cognition and emotion,and its impairment may contribute to the development and progression of depression.Our previous studies have found that Qingyangshen glycosides(QYS)can improve depression-like behavior in social failure mouse models,mainly through PGC-1α/FNDC5/BDNF signaling pathways activation,but its effects and mechanisms on hippocampal neuroplasticity remain unknown.Methods:Chronic social defeat stress(CSDS)was used to induce social defeat in mice.Morphological changes in the hippocampus were observed by H&E staining and Golgi staining.Immunofluorescence double staining was used to detect the expression of synaptophysin(SYN)and postsynaptic density protein-95(PSD-95),while western blot was employed to evaluate PSD-95,SYN,and doublecortin(DCX)proteins.The pathological processing of social defeat and the therapeutic effects of QYS on it was confirmed through behavioral assessment associated with morpho-logic observation.Results:During the whole study,the sucrose preference indices and OFT activity time of CSDS mice were significantly decreased(p≤0.05),and the tail suspension immobil-ity time was significantly increased(p≤0.05),suggesting that the mice had significant depressive symptoms.Treatment with QYS(25,50,and 100 mg/kg)significantly al-leviated depressive symptoms in CSDS mice,which was demonstrated by significantly(p≤0.05 or p≤0.01)reducing the duration of tail-hanging immobility and increasing the tendency of sucrose preference indices and OFT activity time.QYS treatment also significantly increased the expression of DCX,PSD-95,and SYN proteins,which play a crucial role in depression.Conclusions:QYS alleviated these symptoms by enhancing hippocampal neuroplasti-city through upregulating the expression of synapse-associated proteins(SAPs).The therapeutic mechanism of QYS may involve modulating the neuroplasticity of hip-pocampus neurons by altering the expression of SAPs.
基金financially supporting this work through the Large Research Group Project under Grant no.R.G.P.2/509/45
文摘Polyphenols,a diverse group of naturally occurring compounds found in plants,have garnered significant attention for their potential therapeutic properties in treating neurodegenerative diseases(NDs).The Wnt/β-catenin(WβC)signaling pathway,a crucial player in neurogenesis,neuronal survival,and synaptic plasticity,is involved in several cellular mechanisms related to NDs.Dysregulation of this pathway is a hallmark in the development of various NDs.This study explores multiple polyphenolic compounds,such as flavonoids,stilbenes,lignans,and phenolic acids,and their potential to protect the nervous system.It provides a comprehensive analysis of their effects on the WβC pathway,elucidating their modes of action.The study highlights the dual function of polyphenols in regulating and protecting the nervous system,providing reassurance about the research benefits.This review provides a comprehensive analysis of the results obtained from both in vitro studies and in vivo research,shedding light on how these substances influence the various components of the pathway.The focus is mainly on the molecular mechanisms that allow polyphenols to reduce oxidative stress,inflammation,and apoptotic processes,ultimately improving the function and survival of neurons.This study aims to offer a thorough understanding of the potential of polyphenols in targeting the WβC signaling pathway,which could lead to the development of innovative therapeutic options for NDs.
文摘Objective:To isolate and identify active constituents from Gracilaria chorda extract prepared under subcritical water conditions at 210℃(GCSW210)and evaluate their anti-obesity and anti-diabetic effects in 3T3-L1 adipocytes and high-fat diet(HFD)-induced obese zebrafish larvae.Methods:GCSW210 was fractionated through solvent partitioning,ion-exchange chromatography,and silica gel medium-pressure liquid chromatography,followed by preparative high performance liquid chromatography.At each step,bioactivities were assessed in 3T3-L1 adipocytes by Oil Red O staining and 2-NBDG uptake assays.The most active fractions were further purified,and isolated compounds were tested in HFD-induced obese zebrafish larvae.Results:Liquid chromatography-hyphenated analysis with reference standards identified two major compounds in GCSW210:5-hydroxymethylfurfural and bis(5-formylfurfuryl)ether.Both compounds significantly inhibited lipid accumulation in 3T3-L1 adipocytes and modulated gene expression associated with adipogenesis,glucose metabolism,and inflammation in zebrafish.They also enhanced glucose uptake,reduced circulating glucose levels,and improved insulin sensitivity.Notably,the effects were comparable to those of the crude GCSW210 extract.In silico docking studies confirmed stable interactions of both compounds with key metabolic and inflammatory targets,with bis(5-formylfurfuryl)ether showing stronger binding affinities.Conclusions:These findings suggest that 5-hydroxymethylfurfural and bis(5-formylfurfuryl)ether are key contributors to the therapeutic activity of Gracilaria chorda,highlighting its potential as a functional food ingredient for the prevention or management of metabolic disorders.
文摘Traditional Chinese herbal drugs have been used for thousands of years in Chinese pharmacopoeia. The bark of Magnolia officinalis Rehder ＆ E. Wilson, known under the pinyin name ＂Houpo＂, has been traditionally used in Chinese and Japanese medicines for the treatment of anxiety, asthma, depression, gastrointestinal disorders, headache, and more. Moreover, Magnolia bark extract is a major constituent of currently marketed dietary supplements and cosmetic products. Much pharmacological activity has been reported for this herb and its major compounds notably antioxidant, anti-inflammatory, antibiotic and antispasmodic effects. However, the mechanisms underlying this have not been elucidated and only a very few clinical trials have been published. In vitro and in vivo toxicity studies have also been published and indicate some intriguing features. The present review aims to summarize the literature on M. officinalis bark composition, utilisation, pharmacology, and safety.
基金Supported by National Natural Science Foundation of China,No.81001587
文摘Breast cancer is the most common cancer among women. In recent years, many in vitro and in vivo studies indicate that green tea possesses anti-cancer effects. The epidemiological studies, however, have produced inconclusive results in humans. Likewise, results from animal models about the preventive or therapeutic effects of green tea components are inconclusive. The mechanisms by which green tea intake may influence the risk of breast cancer in humans remain elusive. Here, we review recent studies of green tea polyphenols and their applications in the prevention and treatment of breast cancer. Furthermore, we discuss the effect of green tea components on breast cancer by reviewing epidemiological studies, animal model studies and clinical trials. At last, we discuss the mechanisms by which green tea components suppress the develop-ment and recurrence of breast cancer. A better understanding of the mechanisms will improve the utilization of green tea in breast cancer prevention and therapy and pave the way to novel prevention and treatment strategies for breast cancer.
文摘India has a great wealth of various naturally occurring plant drugs which have great potential pharmacological activities.Datura stramonium(D.stramonium is one of the widely well known folklore medicinal herbs.The troublesome weed,D.stramonium is a plant with both poisonous and medicinal preperties and has been proven to have great pharmacological potential with a great utility real usage in folklore medicine.D.stromonium has been scientifically proven to contain alkaloids,tannins,carbohydrates and proteins.This plant has contributed various pharmacological actions in the scientific field of Indian systems of medicines like analgesic and antiasthmatic activities.The present paper presents an exclusive review work on the ethnomedical,phytochemical,pharmacological activities of this plant.
基金by grants from the National Research Foundation,Ministry of Science and ICT,Republic of Korea(NRF-2021R1A2B5B03002123,NRF-2018R1A5A2024425,NRF-2021K2A9A2A06044515,2022M3E5F1017919)Ministry of Education,Republic of Korea(NRF-2021R1A6A3A01086428)Korean Health Technology R&D Project(No.HI19C0664),Ministry of Health&Welfare,Republic of Korea.
文摘Metabolic engineering of the tumor microenvironment has emerged as a new strategy.Lactate dehydrogenase A(LDHA)is a prominent target for metabolic engineering.Here,we designed a cationic lipid nanoparticle formulation for LDHA gene editing.The plasmid DNA delivery efficiency of our lipid nanoparticle formulations was screened by testing the fluorescence of lipid nanoparticles complexed to plasmid DNA encoding green fluorescence protein(GFP).The delivery efficiency was affected by the ratios of three components:a cationic lipid,cholesterol or its derivative,and a fusogenic lipid.The lipid nanoparticle designated formulation F3 was complexed to plasmid DNA co-encoding CRISPR-associated protein 9 and LDHA-specific sgRNA,yielding the lipoplex,pCas9-sgLDHA/F3.The lipoplex including GFP-encoding plasmid DNA provided gene editing in HeLa-GFP cells.Treatment of B16F10 tumor cells with pCas9-sgLDHA/F3 yielded editing of the LDHA gene and increased the pH of the culture medium.pCas9-sgLDHA/F3 treatment activated the interferon-gamma and granzyme production of T cells in culture.In vivo,combining pCas9-sgLDHA/F3 with immune checkpoint-inhibiting anti-PD-L1 antibody provided a synergistic antitumor effect and prolonged the survival of tumor model mice.This study suggests that combining metabolic engineering of the tumor microenvironment with immune checkpoint inhibition could be a valuable antitumor strategy.
文摘Here, we report that the modification of liposome surfaces with AG73 peptides enhances delivery of the lipophilic anticancer drug, edelfosine, to tumor cells overexpressing the cellsurface receptor, syndecan 2. To test the effect of liposomal surface density of AG73 peptides on cellular uptake, we synthesized AG73 peptide-conjugated polyethylene glycol(MW 2000)lipid and incorporated it into fluorescence dye-labeled anionic liposomes with different ligand densities(1, 2, or 5 mol% of total lipids). Cellular uptake of AG73-peptide–modified liposomes gradually increased in proportion to the surface ligand density. The percentages of cells positive for AG73-modified, fluorescent-dye–labeled liposomes were 19.8 ± 2.0%, 23.1 ± 5.0%,and 99.2 ± 1.0%, for ligand mole percentages of 1, 2, and 5, respectively. The cell-targeting ability of AG73-modified liposomes was not significantly altered by the serum content of culture media. In keeping with the observed enhanced cellular uptake, AG73-peptide–modified liposomes entrapping edelfosine exhibited greater cancer cell-killing effects compared with unmodified liposomes. Following intravenous administration into tumor-bearing mice,AG73-peptide–modified liposomes showed 2.1-fold greater accumulation in tumors than unmodified liposomes. These results support the feasibility of using syndecan 2–directed liposomes for delivery of edelfosine.
基金the grants from National Natural Science Foundation of China(21602030 and 81872808)Program of Shanghai Academic Research Leader(18XD1400500)+2 种基金Project Supported by Shanghai Municipal Science and Technology Major Project(2018SHZDZX01)ZJLab,Fudan-SIMM Joint Research Fund(FU-SIMM20182006)Scientific Research Program of Shanghai Health and Family Planning Commission(20184Y0149).
文摘Although current anticancer immunotherapies using immune checkpoint inhibitors(ICIs)have been reported with a high clinical success rate,numerous patients still bear‘cold’tumors with insufficient T cell infiltration and low immunogenicity,responding poorly to ICI therapy.Considering the advancements in precision medicine,in-depth mechanism studies on the tumor immune microenvironment(TIME)among cold tumors are required to improve the treatment for these patients.Nanomedicine has emerged as a promising drug delivery system in anticancer immunotherapy,activates immune function,modulates the TIME,and has been applied in combination with other anticancer therapeutic strategies.This review initially summarizes the mechanisms underlying immunosuppressive TIME in cold tumors and addresses the recent advancements in nanotechnology for cold TIME reversal-based therapies,as well as a brief talk about the feasibility of clinical translation.
基金supported by grants from the Ministry of Science and ICT,Republic of Korea(NRF-2018R1A2A1A05019203,NRF-2018R1A5A2024425)the Korean Health Technology R&D Project(No.HI15C2842,HI18C2177,HI19C0664),Ministry of Health&Welfare,Republic of Korea.
文摘We report the activation of anticancer effector functions of T cells through nanoparticle-induced lipid metabolic reprogramming.Fenofibrate was encapsulated in amphiphilic polygamma glutamic acid-based nanoparticles(F/ANs),and the surfaces of F/ANs were modified with an anti-CD3e f(ab′)2 fragment,yielding aCD3/F/ANs.An in vitro study reveals enhanced delivery of aCD3/F/ANs to T cells compared with plain F/ANs.aCD3/F/AN-treated T cells exhibited clear mitochondrial cristae,a higher membrane potential,and a greater mitochondrial oxygen consumption rate under glucose-deficient conditions compared with T cells treated with other nanoparticle preparations.Peroxisome proliferatoractivated receptor-αand downstream fatty acid metabolismrelated genes are expressed to a greater extent in aCD3/F/AN-treated T cells.Activation of fatty acid metabolism by aCD3/F/ANs supports the proliferation of T cells in a glucose-deficient environment mimicking the tumor microenvironment.Real-time video recordings show that aCD3/F/AN-treated T cells exerted an effector killing effect against B16F10 melanoma cells.In vivo administration of aCD3/F/ANs can increase infiltration of T cells into tumor tissues.The treatment of tumor-bearing mice with aCD3/F/ANs enhances production of various cytokines in tumor tissues and prevented tumor growth.Our findings suggest the potential of nanotechnology-enabled reprogramming of lipid metabolism in T cells as a new modality of immunometabolic therapy.
文摘Purpose: This study was conducted to audit prophylactic antibiotic use and to quantify the rate of wound infection. Methods: Across-sectional prospective study was conducted in the Obstetrics and Gynecology Department in Khartoum Teaching Hospital, Sudan during March 1st to 31st October 2010. All Patients (aged >18 years) were included. Results: Overall 725 patients were included. The performed surgical procedures were 751;of these 578 (76.9%) were Caesarean sections. Overall rate of wound infection was 7.8%. The rate of wound infection among patients operated on for caesarean section and abdominal hysterectomy was 8.3%, and 9.2%, respectively. Multivariate logistic analysis showed that body mass index [BMI] ≥ 30 kg/m2 OR 2.1, 95% CI (1.1 - 4.0), (P = 0.019) was the major independent risk factor for occurrence of wound infection. Evaluation of prescriptions’ parameters against the stated criteria showed that 113 (15.8%) patients were given antibiotics with adequate spectrum of activity, 611 (85.3%) given sub-dose/s, 83 (11.6%) received the first preoperative dose/s in a proper time window, and 716 (100%) had prophylaxis for extended duration. Overall conformity to the stated criteria for the evaluation of prescription’s parameters was not achieved in all prescriptions. Conclusions: In this setting, antibiotics were irrationally used and wound infection rate was high, and the situation calls for multiple interventions to correct the situation, through the activation of the infection control committee in the hospital and development of antimicrobial subcommittee to develop policies for the use and auditing of prophylactic antibiotics.
文摘Obesity is often identified as a nutritional disorder, and this condition continues to be one of the most important yet preventable health hazards. It may be a complex group of diseases and should be characterized as a syndrome that results from an imbalance between energy intake and expenditure. Furthermore, obesity is associated with several diseases such as diabetes mellitus, atherosclerosis, cardiovascular diseases, osteoarthritis, and hypertension. In previous studies, we found that in Asia, especially in the Asean region, carbohydrates are heavily represented in the diet. Therefore, we used a high carbohydrate diet to induce obesity in rats. The aim of this study was to evaluate the potency of Tamarindus indica pulp as an anti-obesity agent in a high carbohydrate diet animal model. The antiobesity effect was evaluated in this in vivo model at doses of 75 mg/kg·bw and 225 mg/kg·bw. Treatment was started in week 3 and week 9, and biochemical characteristics were measured every 3 weeks. In the end of the study period, insulin resistance and adiponectin levels were measured. TIWE(Tamarindus indica water extract) at a dose of 75 mg/kg·bw showed better efficacy than at a dose of 225 mg/kg·bw, and treatment started on week 3 was better than treatment started on week 9. TIWE has an anti-obesity effect associated insulin resistance by increasing adiponectin levels and insulin sensitivity, which can impact body weight, triglyceride levels, blood glucose levels, and body fat.
文摘OBJECTIVE： The roots of Chlorophytum borivilanum are used in traditional medicine for the treatment of arthritis and inflammation. The aim of the work was to evaluate the anti-inflammatory activity of isolated saponins from Chlorophytum borivilianum （ISCB）. METHODS： The ISCB was screened using the carrageenan-induced paw edema, histamine-induced paw edema, cotton pellet-induced granuloma, and Freund＇s adjuvant-induced arthritis in rats at orally administered doses of 3, 10, and 30 mg/kg. Effect of ISCB on histone deacetylase （HDAC） level was measured by the HDAC assay at the highest dose （30 mg/kg）. RESULTS： The results showed that the ISCB significantly reduced carrageenan-induced inflammation, histamine-induced inflammation, cotton pellet-induced granuloma and Freund＇s adjuvant-induced arthritis in rats. The ISCB at a dose of 30 mg/kg significantly inhibited HDAC level in rat paw tissue. CONCLUSION： It is concluded that saponins isolated from roots of C. borivilianum possess anti- inflammatory and anti-arthritic properties. ISCB may act by inhibiting histamine, prostaglandin and HDAC. This suggests that ISCBs have potential for therapeutic use in the treatment of inflammation and arthritis
基金This work was supported by grants from the Korean Health Technology R&D project,Ministry of Health and Welfare(Grant No.A092010)from Ministry of Science,ICT and Future Planning(No.2014023227)from Business for Cooperative R&D between Industry,Academy,and Research Institute funded Korea Small and Medium Business Administration(No.C0010962).
文摘Despite the progress of conventional vaccines,improvements are clearly required due to concerns about the weak immunogenicity of these vaccines,intrinsic instability in vivo,toxicity,and the need for multiple administrations.To overcome such problems,nanotechnology platforms have recently been incorporated into vaccine development.Nanocarrier-based delivery systems offer an opportunity to enhance the humoral and cellular immune responses.This advantage is attributable to the nanoscale particle size,which facilitates uptake by phagocytic cells,the gut-associated lymphoid tissue,and the mucosa-associated lymphoid tissue,leading to efficient antigen recognition and presentation.Modifying the surfaces of nanocarriers with a variety of targeting moieties permits the delivery of antigens to specific cell surface receptors,thereby stimulating specific and selective immune responses.In this review,we introduce recent advances in nanocarrierbased vaccine delivery systems,with a focus on the types of carriers,including liposomes,emulsions,polymer-based particles,and carbon-based nanomaterials.We describe the remaining challenges and possible breakthroughs,including the development of needlefree nanotechnologies and a fundamental understanding of the in vivo behavior and stability of the nanocarriers in nanotechnology-based delivery systems.
基金The training and education of staff and workers of enterprises in Shandong province key project(2014-223)The graduate education innovation project of Shandong province(SDYY12004)Binzhou Medical University adult education teaching and research projects(BY-CJY201203,JYKT201215,13-rwjykt-003)
文摘Nowadays,with the expanding enrollment of medical schools in our country,the competitive pressures of employment increase.It is very difficult for the graduates of these schools to find ideal jobs,but medical students with master or doctor degrees are relatively optimistic to the employment situation.As a result,more and more fresh medical graduates pursue the post-graduate education,thus forms a"rush of taking test of postgraduate"phenomenon[1].Clinical students
基金Supported by Tehran University of Medical Sciences(Grant No.92-03-96-24313)
文摘Considering the fact that liver is one of the most important organs in our body,it deserves special attention and protection.Among various recommended supplements,complementary and alternative medicines particularly herbal remedies have received much attention owing to their truly healing properties.This review profits from Iranian traditional medicine and presents advantageous herbal guide directions for liver protection.According to credible Iranian medical literature such as Al Qanun Fil Tibb.Al-Havi and Makhzan-al-Aadvia.a wide spectrum of plants have been found to be useful for cleansing and protecting the liver.Some herbs such as ghafes(Agrimonia eupatoria),kasni(Cichorium intybus),anar(Punica granatum),darchin(Cinnamomum zeylanicum),za'feran(Crocus sativus),gole-sorkh(Rosa damascena) and zereshk(Berberis vulgaris) appeared to get strong consideration and were well documented as outstanding liver tonics.We conducted a comprehensive review of available Iranian medical resources such as scientific information database and medical sciences databases which cover all in vitro and in vivo studies of medicinal plants as liver tonics and hepatoprotcctive candidates.Literature survey was accomplished using multiple databases including PubMed,ISI web of knowledge,and Google Scholar.
文摘Strategies for CADD vary depending on the extent of structural and other information available regarding the target (enzyme/receptor) and the ligands. Computer-aided drug design (CADD) is an exciting and diverse discipline where various aspects of applied and basic research merge and stimulate each other. In the early stage of a drug discovery process, researchers may be faced with little or no structure activity relationship (SAR) information. The process by which a new drug is brought to market stage is referred to by a number of names most commonly as the development chain or “pipeline” and consists of a number of distinct stages. To design a rational drug, we must firstly find out which proteins can be the drug targets in pathogenesis. In present review we reported a brief history of CADD, DNA as target, receptor theory, structure optimization, structure-based drug design, virtual high-throughput screening (vHTS), graph machines.
文摘Background Influenza vaccination has been clinically shown to reduce adverse cardiovascular outcomes in acute coronary syndrome （ACS） patients, but the economic perspectives can provide important data to make informed decisions. This study aimed to perform the economic evaluation of lifelong annual influenza vaccination for cardiovascular events and well-established pneumonia prevention. Methods Lifetime costs, life-expectancy, and quality-adjusted live years （QALYs） were estimated beyond one-year cycle length of a six-health states Markov model condition on whether a hospitalization for ACS, stroke, heart failure, pneumonia, no hospitalizations occurred, or death. The comparison of three age-groups of 40-49, 50-65, and 〉 65 years scenario was performed. Incremental cost-effectiveness ratio （ICER） and net monetary benefit （NMB） were presented as a societal perspective in 2016. The model robustness was determined by one-way and prob- abilistic sensitivity analyses. Results The influenza vaccination was cost-effective in all age-groups, by dominant ICERs （lower cost with higher effectiveness） which was completely lower than acceptable willingness-to-pay threshold of Thailand [160,000 THB （4,466.8 USD） per QALYs], with a great incremental value of NMB. Especially, the 50-year-old-and- above scenario was shown as the most benefit at 129,092 THB （3,603.9 USD） for each patient. Conclusions The annually additional influenza vaccination to standard treatment in ACS was cost-effective in all age-groups, which should be considered in clinical practice and health-policy making process.
