Sepsis is characterized by a severe and life-threatening host immune response to polymicrobial infection accompanied by organ dysfunction.Studies on the therapeutic effect and mechanism of immunomodulatory drugs on th...Sepsis is characterized by a severe and life-threatening host immune response to polymicrobial infection accompanied by organ dysfunction.Studies on the therapeutic effect and mechanism of immunomodulatory drugs on the sepsis-induced hyperinflammatory or immunosuppression states of various immune cells remain limited.This study aimed to investigate the protective effects and underlying mechanism of artesunate(ART)on the splenic microenvironment of cecal ligation and puncture-induced sepsis model mice using single-cell RNA sequencing(scRNA-seq)and experimental validations.The scRNA-seq analysis revealed that ART inhibited the activation of pro-inflammatory macrophages recruited during sepsis.ART could restore neutrophils’chemotaxis and immune function in the septic spleen.It inhibited the activation of T regulatory cells but promoted the cytotoxic function of natural killer cells during sepsis.ART also promoted the differentiation and activity of splenic B cells in mice with sepsis.These results indicated that ART could alleviate the inflammatory and/or immunosuppressive states of various immune cells involved in sepsis to balance the immune homeostasis within the host.Overall,this study provided a comprehensive investigation of the regulatory effect of ART on the splenic microenvironment in sepsis,thus contributing to the application of ART as adjunctive therapy for the clinical treatment of sepsis.展开更多
Tumor microenvironment(TME)with the particular features of severe hypoxia,insufficient endogenous H2O2,and overexpression of glutathione(GSH)markedly reduced the antitumor efficacy of monotherapy.Herein,a TME-responsi...Tumor microenvironment(TME)with the particular features of severe hypoxia,insufficient endogenous H2O2,and overexpression of glutathione(GSH)markedly reduced the antitumor efficacy of monotherapy.Herein,a TME-responsive multifunctional nanoplatform(Bi2S3@Bi@PDA-HA/Art NRs)was presented for synergistic photothermal therapy(PTT),chemodynamic therapy(CDT),and photodynamic therapy(PDT)to achieve better therapeutic outcomes.The Z-scheme heterostructured bismuth sulfide@bismuth nanorods(Bi2S3@Bi NRs)guaranteed excellent photothermal performance of the nanoplatform.Moreover,its ability to produce O2 and reactive oxygen species(ROS)synchronously could relieve tumor hypoxia and improve PDT outcomes.The densely coated polydopamine/ammonium bicarbonate(PDA/ABC)and hyaluronic acid(HA)layers on the surface of the nanoplatform enhanced the cancer-targeting capacity and induced the acidic TME-triggered in situ“bomb-like”release of Art.The CDT treatment was achieved by activating the released Art through intracellular Fe2+ions in an H2O2-independent manner.Furthermore,decreasing the glutathione peroxidase 4(GPX4)levels by Art could also increase the PDT efficiency of Bi2S3@Bi NRs.Owing to the synergistic effect,this nanoplatform displayed improved antitumor efficacy with minimal toxicity both in vitro and in vivo.Our design sheds light on the application of phototherapy combined with the traditional Chinese medicine monomer-artesunate in treating the hypoxic tumor.展开更多
Diabetes is a metabolic disease characterized by abnormally elevated blood glucose levels.Persistent hyperglycemia leads to diabetic nephropathy,diabetic retinopathy,diabetes with periodontal disease and other diabeti...Diabetes is a metabolic disease characterized by abnormally elevated blood glucose levels.Persistent hyperglycemia leads to diabetic nephropathy,diabetic retinopathy,diabetes with periodontal disease and other diabetic complications.These diseases have become the main causes of disability and death in diabetic patients.Artesunate is well known as an antimalarial drug for controlling malaria symptoms.Current studies have shown that artesunate improves diabetes and its complications by protecting islet cells,improving glucose and lipid metabolism,anti-inflammatory and immune regulation.Based on the research status in recent years,this paper focuses on the mechanism of artesunate in diabetes and its complications,to provide a theoretical basis for future diabetes research.展开更多
The combination of Artesunate (ART) and Paclitaxel (PTX) in two human prostate cancer (PCa) cell lines (PC-3 and LNCaP) was evaluated to investigate the effects on proliferation, apoptosis and morphological changes. T...The combination of Artesunate (ART) and Paclitaxel (PTX) in two human prostate cancer (PCa) cell lines (PC-3 and LNCaP) was evaluated to investigate the effects on proliferation, apoptosis and morphological changes. The half maximal inhibitory concentration (IC<sub>50</sub>) values that were observed by ART and PTX on both LNCaP and PC-3 cell lines at 72-and 120-hour exposure were used to assess these effects. Early and late apoptosis was detected in Annexin V-FITC/PI assay revealed a shift in population of cells towards early and mid-apoptosis with ART + PTX than with ART and PTX individually. More effects were observed on LNCaP cell lines at both 72-hour and 120-hour exposure. The results for the Caspase 3/7 activity assay showed shift of viable population in all induced samples compared to control. Morphological changes occurred in both cell lines;this was validated in qualitative assessment when examined under the inverted microscope. These findings indicated that ART + PTX suppressed PCa cell proliferation in a dose- and time-dependent manner.展开更多
AIM: To evaluate the effect of artesunate(AS) supplementation on bacterial translocation(BT) and gut microbiota in a rat model of liver cirrhosis. METHODS: Fifty-four male Sprague-Dawley rats were randomly divided int...AIM: To evaluate the effect of artesunate(AS) supplementation on bacterial translocation(BT) and gut microbiota in a rat model of liver cirrhosis. METHODS: Fifty-four male Sprague-Dawley rats were randomly divided into a normal control group(N), a liver cirrhosis group(M) and a liver cirrhosis group intervened with AS(MA). Each group was sampled at 4, 6 and 8 wk. Liver cirrhosis was induced by injection of carbon tetrachloride(CCl4), intragastric administration of 10% ethanol, and feeding a high fat diet. Rats in the MA group were intragastrically administered with AS(25 mg/kg body weight, once daily). Injuries of the liver and intestinal mucosa were assessed by hematoxylineosin or Masson's trichrome staining. Liver index was calculated as a ratio of the organ weight(g) to body weight(g). The gut microbiota was examined by automated ribosomal intergenic-spacer analysis of fecal DNA. BT was assessed by standard microbiological techniques in the blood, mesenteric lymph nodes(MLNs), liver, spleen, and kidney. RESULTS: Compared to group N, the body weight was reduced significantly in groups M and MA due to the development of liver cirrhosis over the period of 8 wk. The body weight was higher in group MA than in group M. The liver indices were significantly elevated at 4, 6 and 8 wk in groups M and MA compared to group N. AS supplementation partially decreased the liver indices in group MA. Marked histopathologic changes in the liver and small intestinal mucosa in group M were observed, which were alleviated in group MA. Levels of pro-inflammatory interleukin-6 and tumor necrosis factor-α were significantly elevated at 8 wk in ileal homogenates in group M compared to group N, which were decreased after AS supplementation in group MA. The dysbiosis of gut microbiota indicated by the mean diversity(Shannon index) and mean similarity(Sorenson index) was severe as the liver cirrhosis developed, and AS supplementation had an apparent intervention effect on the dysbiosis of gut microbiota at 4 wk. The occurrence of BT was increased in the liver of group M compared to that of group N. AS supplementation reduced BT in group MA at 8 wk. BT also occurred in the MLNs, spleen, and kidney, which was reduced by AS supplementation. BT was not detected in the blood in any group.CONCLUSION: Dysbiosis of gut microbiota, injury of intestinal mucosal barrier and BT occurred as liver cirrhosis progressed, which might enhance inflammation and aggravate liver injury. AS may have other nonantimalarial effects that modulate gut microbiota,inhibit BT and alleviate inflammation, resulting in a reduction in CCl4, alcohol and high fat-caused damages to the liver and intestine.展开更多
AIM:To study the braking effectiveness of artesunate on transforming growth factor(TGF)-β2 mediated epithelial-mesenchymal transition(EMT)in retinal pigment epithelium(RPE)in vitro.METHODS:The fostered ARPE-19 cells ...AIM:To study the braking effectiveness of artesunate on transforming growth factor(TGF)-β2 mediated epithelial-mesenchymal transition(EMT)in retinal pigment epithelium(RPE)in vitro.METHODS:The fostered ARPE-19 cells were processed with artesunate alone or combined with the TGF-β2.The CCK-8 examination was utilized to test the cell propagation.Cell migration was detected by scratch as well as the Transwell examination.The EMT characters and activation of PI3K/Akt signal channel were estimated by Western blotting and immunofluorescence.The Western blotting was utilized in order to confirm the vitreous of controls as well as patients with proliferative vitreoretinopathy(PVR)were collected and the levels of PI3K,phospho-PI3K,Akt.RESULTS:Disposal of ARPE-19 cells with artesunate(50-150μmol/L)obviously suppressed their propagation and immigration,which dependent on the concentration and time.Artesunate suppressed the EMT which was induced by TGF-β2 in ARPE-19 cells through sustaining the expression of vimentin andα-SMA through the suppression of PI3K,phospho-PI3K,phospho-Akt and Akt.Levels of PI3K,phospho-PI3K,AKT and phospho-Akt was increased in the vitreous in PVR(P<0.05).CONCLUSION:Such findings indicate that PI3K/Akt signal channel is highly activated in vitreous of PVR.Artesuante is an operative depressor of the propagation,immigration and TGF-β2-mediated EMT of ARPE-19 cells by reduced the expression of PI3K/Akt channel.展开更多
OBJECTIVE To investigate the genome protective effects of anti-malaria drug,artesunate in an experimental allergic asthma model.METHODS Mice were sensitized on day 0 and 7 and challenged on day 14 with 100μg house du...OBJECTIVE To investigate the genome protective effects of anti-malaria drug,artesunate in an experimental allergic asthma model.METHODS Mice were sensitized on day 0 and 7 and challenged on day 14 with 100μg house dust mite(HDM)via intratracheal administration.Artesunate(30mg·kg-1)was administered intra-peritoneally on day 6,7,8,13,14 and 15.Samples were collected on day 1,3 and 5 post last HDM-challenge for analysis of air way inflammation and DNA damage.Lung sections were immunofluorescence(IF)-stained for DNA double strand breaks(DSBs)markers,γH2AX and 53BP1.Levels of DNA repair proteins Ku70 and Rad51,which are involved in non-homologous end joining(NHEJ)and homologous recombination(HR)DNA DSB repair pathways respectively,were measured.To quantify cell death in asthmatic lung,TUNEL staining was performed.Comet assay,a single cell gel electrophoresis was employed to detect DNA damage induced by HDM in BEAS-2Bhuman bronchial epithelial cell line,in vitro.RESULTS Artesunate treatment significantly reduces immune cells infiltration in BAL fluid of asthmatic mice,collected on day 3 and 5 post-challenge.Importantly,artesuante is able to protect bronchial epithelium from DNA DSBs induced by asthma,as detected by the reduced level of γH2AX and 53BP1 foci formation in the nucleus.This genome protective effect is evident even on day 1 post-challenge,when immune cells infiltration remained high.This indicates that artesunate confers protection on bronchial epithelium in the presence of inflammation.Additionally,artesunate is also able to reduce cell death in asthmatic lung revealed by TUNEL assay and cleaved caspase 3 level.Interestingly,the levels of DNA repair proteins in artesuante-treated asthmatic mice are unchanged as compared to HDM-only mice,suggesting that artesunate treatment does not augment the level of DNA repair proteins.When human bronchial epithelial BEAS-2 Bcells were exposed to HDMin vitro,we observed an increase in the levels of DNA damage.Artesunate(60μmol·L-1)co-incubated with HDM is not able to prevent direct DNA damage induced by the allergen.Together,these studies suggest that the genome protective effect of artesunate in vivo may be attributed to physiological effects(such as its anti-inflammatory effects)rather than serving to directly prevent DNA damage.CONCULSION This study highlights a novel role for artesunate in protecting bronchial epithelial cells from asthma-induced DNA damage.展开更多
Introduction: Severe malaria is one of the leading causes of death in Sub-Saharan African countries, and artesunate is recommended as a first-line treatment by the Word Heath Organization (WHO.). Objective: Identify t...Introduction: Severe malaria is one of the leading causes of death in Sub-Saharan African countries, and artesunate is recommended as a first-line treatment by the Word Heath Organization (WHO.). Objective: Identify the advantages of artesunate compared with quinine in the treatment of severe malaria in children. Methods and patients: This study was a cross-sectional, descriptive and analytical study focused on children hospitalized for severe malaria in the CNHU who were treated with quinine or artesunate. Findings: The hospital-based frequency rate of severe malaria in pediatric patients was estimated to be 28.3% (n = 848). One hundred five children were treated with artesunate, and 743 were treated with quinine. The mean age of the children was 47 months old. The primary signs of severity were anemia (n = 776), neurological manifestations (n = 309) and hemolysis (n = 137). The average duration of treatment was 1.95 days for artesunate versus 2.45 days for quinine, and the difference was statistically significant (p = 0.001). The average length of stay (ALOS) in the hospital was 5 days for the artesunate group versus 5.75 days for the quinine group, and the difference was statistically significant (p < 0.001). Six of the children who received artesunate died, whereas 24 children who treated with quinine died. The total average cost of healthcare was 50,600 FCFA (77 euros) per child treated with artesunate versus 57,100 FCFA (87 euros) per child treated with quinine. Conclusion: The treatment of severe malaria with artesunate is superior to quinine-based treatment.展开更多
Objective:To determine the suppressive and curative activity of aqueous leaf extract of Ageratum conyzoides(A.conyzoides) in combination with chloroquine and artesunate, respectively against Plasmodium berghei infecti...Objective:To determine the suppressive and curative activity of aqueous leaf extract of Ageratum conyzoides(A.conyzoides) in combination with chloroquine and artesunate, respectively against Plasmodium berghei infection in mice.Methods:Using malaria(Plasmodium berghei) infected albino mice of both sexes,aqueous extracts of A.conyzoides in combination with chloroquine and artesunate were tested for antimalarial activity,respectively.Four-day suppressive test and Rane’s curative test were carried out.Results:Suppressive tests showed significant dose dependent reduction in parasitemia level produced by the extract-chloroquine and extract-artesunate combinations.Suppressive activities of both extract-drug combinations were greater than the individual drugs alone.Extract-chloroquine(100:5) produced the highest suppressive effect(98%suppression).Curative tests showed absolute survival in two extract-drug combinations.Two extract-drug combinations produced higher curative effects than the individual drugs alone.The highest dose combinations of extract-chloroquine(100:5) and extract-artesunate(100:5) produced absolute parasitemia clearance(cure) in the infected mice. Conclusions:The study indicated that aqueous extract of A.conyzoides had the ability to potentiate the antimalarial activity of chloroquine and artesunate against induced plasmodiasis in mice.It contributes a lot in the malaria endemic and poverty stricken tropics.展开更多
Objective:To explore larvicidal effects of anthelmintic drugs on Opisthorchis viverrini(O.viverrini) for alternative approach to interrupting its cycle for developing a field-based control program.Methods:The larvicid...Objective:To explore larvicidal effects of anthelmintic drugs on Opisthorchis viverrini(O.viverrini) for alternative approach to interrupting its cycle for developing a field-based control program.Methods:The larvicidal activities of albendazole(A1),artesunate(Ar),praziquantel(Pzq) and miltefosine(Mf) on O.viverrini cercariae and mature metacercariae were investigated.Lethal concentrations(LC_(50) and LC_(95)) of these drugs were determined.Mature metacercariae previously exposed to various concentrations of the drugs were administered to hamsters.Worms were harvested 30 d post infection and worm recovery rates calculated.Al,Ar,Pzq and Mf produced morphological degeneration and induced shedding tails of cercariae after 24 h exposure.Results:The LC_(50) and LC_(95) of Al,Ar,Pzq and Mf on cercariae were 0.720 and 1.139,0.350 and 0.861,0.017 and 0.693,and 0.530 and 1.134 ppm,respectively.LC_(50) and LC_(95) of Ar on mature metacercariae were 303.643 and 446.237 ppm and of Mf were 289.711 and 631.781 ppm,respectively but no lethal effect in Pzq-and Al-treated groups(up to 1 ppt).No worms were found in hamsters administered Pzq-treated metacercariae.The adult worms from Al-treated metacercariae were significantly bigger in size compared to the control group(P<0.05).Fecundity and body width were greater in adults from Mf-treated metacercariae compared to the control group(P<0.05).Conclusions:The larvicidal effects of these drugs were high efficacy to O.viverrini cercariae but lesser efficacy to metacercariae.It should be further studied with the eventual aim of developing a field-based control program.展开更多
Artesunate, an antimalarial drug, has been shown to inhibit the release of inflammatory mediators in various disease conditions. The present study was carried out to evaluate the anti-edematogenic effect of arte- suna...Artesunate, an antimalarial drug, has been shown to inhibit the release of inflammatory mediators in various disease conditions. The present study was carried out to evaluate the anti-edematogenic effect of arte- sunate in the rat paw edema model. Inflammation was induced in the hind paw of rat by sub-plantar injection of 0.1 mL of 0.5% carrageenan and the paw volume was measured up to a fixed mark just before the injection and then after 3 h. The difference in two volumes gave a measure of edema formation. At 3h the level of TNF-α, PGE_(2) and myeloperoxidase were estimated in the inflamed paw tissue. Treatment of rats with single dose of artesunate at 50 and 150 mg/kg produced a dose-dependent inhibition in paw inflammation where a significant reduction in edema volume and mediator release was observed. Our study shows that by inhibiting the release of inflam- matory mediators artesunate affords protection against acute inflammation induced in the rat paw and suggests that it has a potential to be used in the treatment of inflammatory disease conditions.展开更多
Effects of amodiaquine, artesunate and artesunate amodiaquine combination on open field novelty-induced behaviors and spatial memory in healthy mice were studied. Forty mice were used in the open field and fifty each ...Effects of amodiaquine, artesunate and artesunate amodiaquine combination on open field novelty-induced behaviors and spatial memory in healthy mice were studied. Forty mice were used in the open field and fifty each in the radial arm maze and Y maze;mice were assigned into four or five groups of ten each, Group A served as control (distilled water), Groups B, C and D received artesunate (4 mg/kg), amodiaquine (10 mg/kg) and artesunate-amodiaquine combination (4 mg/kg and10 mg/kg) respectively, while Group E animals (for the cognition tests) were given scopolamine (2 mg/kg). Drugs and vehicle were administered orally for three days. Results were analysed by one way analysis of variance followed by a posthoc test. Results showed that artesunate and amodiaquine either in combination or administered singly caused a significant increase in open field novelty-induced horizontal locomotion and rearing. Grooming in the open field showed increments in the artesunate alone and artesunate amodiaquine groups while significant reductions in spatial memory were also seen in the cognition models used.展开更多
Alzheimer disease is one of the commonest neurological diseases which is characterized by amyloid plaques accumulation in multiple brain regions. This study investigated the potential neuroprotective effect of artesun...Alzheimer disease is one of the commonest neurological diseases which is characterized by amyloid plaques accumulation in multiple brain regions. This study investigated the potential neuroprotective effect of artesunate on aluminum induced neurotoxicity vs memantine in rats. 40 male albino Wistar rats were divided randomly into 4 groups as follow: Group 1 negative control, group 2 positive control group induced by ammonium chloride, group 3 rats treated by NH4Cl + artesunate solution, group 4 rats treated by NH4Cl + memantine S.C. spatial Memory and Learning were evaluated using Morris Water Maze (MWM) test. Malondialdehyde (MDA) and reduced glutathione (GSH) levels were measured in cerebral cortex tissue homogenate. Tumor necrosis factor-α (TNFα) and interleukin-1 beta (IL-1β) concentrations were measured in rat cerebral cortex tissue homogenate using rat enzyme linked immunosorbent assay (ELISA) kits. Real-time quantitative reverse transcription-polymerase chain reaction (Real-time qRT-PCR) for Caspase-3, Bcl-2 and iNOS gene expression was measured in rat cerebral cortex. Slices from cerebral cortex were studied by histopathological examination. Artesunate significantly decreased MDA level and inhibited iNOS, caspase and upregulated Bcl-2 gene expression in cerebral cortex. ART increased significantly antioxidant level GSH, and decreased significantly TNF-alpha and IL-B levels. It reduced significantly 1ry retention latency, 2ry retention latency and initial acquisition latency. It also improved brain histopathology and decreased amyloid plaque deposition. ART exerted neuroprotective effect through oxidative stress correction and enhancement of antiapoptotic markers in neuronal cells of the cerebral cortex.展开更多
Introduction: Artemisinin-based combination therapies are the first-line antimalarial drugs used to treat uncomplicated Plasmodium falciparum malaria in many endemic countries worldwide. In Chad, since the adoption of...Introduction: Artemisinin-based combination therapies are the first-line antimalarial drugs used to treat uncomplicated Plasmodium falciparum malaria in many endemic countries worldwide. In Chad, since the adoption of artemisinin-based combination therapy (ACTs) in its first-line treatment policy for uncomplicated malaria in 2005, Artemether-Lumefantrine and Artesunate-Amodiaquine have been used in many hospitals and health centers. The main objective of this study was to provide the baseline data of Artemether-Lumefantrine and Artesunate-Amodiaquine efficacy in three regions where many people suffered from malaria disease. Material and Methods: The baseline efficacy of two combination therapies was evaluated between January and April 2020 in Mosoro, Mondou and Dourbali Provinces in Chad. A two-arm single cohort study was conducted to assess the clinical efficacy of artesunate-amodiaquine and artemether-lumefantrine for the treatment of 1113 children aged from 6 to 59 months with uncomplicated Falciparum malariae diagnosed by thick blood smear examination, using the World Health Organization validated protocol. Results: On day 3, all patients in both groups had cleared parasitemia, after treatment, the patients presented a higher hemoglobin level in both groups artemether-lumefantrine (10.97 ± 1.39) and artesunate-amodiaquine (11.87 ± 1.81), respectively. On day 28, all patients had adequate clinical and parasitological responses with 99.82% of artesunate-amodiaquine and 99.10% of artemether-lumefantrine. Overall, both drugs were well tolerated at the clinical and biological level, no late parasitological failures have been recorded in artemether-lumefantrine and artesunate-amodiaquine groups, also both forms of Artemisinin-based combination therapy were still effective and safe in the treatment of uncomplicated P. falciparum malaria in Chad.展开更多
Purpose: The objective of this study was to investigate the anti-tumor effects and analyze the mechanism of artesunate(ART) action on breast cancer in vivo using tumor transplanted nude mice.Methods: The human breast ...Purpose: The objective of this study was to investigate the anti-tumor effects and analyze the mechanism of artesunate(ART) action on breast cancer in vivo using tumor transplanted nude mice.Methods: The human breast tumor cell line MCF-7 was transplanted into nude mice, and the animals were treated with various doses of ART alone or in combination with cyclophosphamide(CTX) or normal saline(NS). The tumor inhibitory effects were observed and compared, and the ultrastructural morphology of the transplanted tumor cells was observed by electron microscopy. The apoptosis rates and cell cycle status were detected by flow cytometry(FCM). The expression of apoptosis-related proteins p53, Bcl-2, Bax and Caspase-3 were detected by immunohistochemistry and IGF-IR was detected by western blot. The expression correlation for these proteins was also analyzed.Results: The tumor inhibition rates in the low dose ART group, high dose ART group, CTX group and combined drug therapy group were(24.39±10.20)%,(40.24±7.02)%,(57.01±5.84)% and(68.29±5.1)%, respectively. The cell cycle was arrested in phase G0/G1 after treatment with ART. The expression of Bcl-2 was significantly reduced, and the expression levels of Bax and Caspase-3 were significantly increased in the ART group compared to the negative control saline group. There was no significant difference detected in p53 expression. The Bcl-2 level was negatively related to Bax and Caspase-3. The western blotting results showed IGF-IR downregulation.Conclusions: ART inhibits the growth of MCF-7 breast tumor cell xenografts in nude mice. The antitumor mechanism of ART for human breast carcinoma in nude mice might be correlated with the alteration of apoptosis related protein expression, which may further induce apoptosis and inhibit cell proliferation.展开更多
Objective To investigate the possible effect of artesunate(ART) on schistosome thioredoxin glutathione reductase(TGR) and cytochrome c peroxidase(CcP) in Schistosoma mansoni-infected mice. Methods A total of 200 labor...Objective To investigate the possible effect of artesunate(ART) on schistosome thioredoxin glutathione reductase(TGR) and cytochrome c peroxidase(CcP) in Schistosoma mansoni-infected mice. Methods A total of 200 laboratory bred male Swiss albino mice were divided into 4 groups(50 mice in each group). Group I: infected untreated group(Control group) received a vehicle of 1% sodium carbonyl methylcellulose(CMC-Na); Group II: infected then treated with artesunate; Group III: infected then treated with praziquantel, and group IV: infected then treated with artesunate then praziquantel. Adult S. mansoni worms were collected by Animal Perfusion Method, tissue egg counted, TGR, and CcP mRNA Expression were estimated of in S. mansoni adult worms by semi-quantitative rt-PCR. Results Semi-quantitative rt-PCR values revealed that treatment with artesunate caused significant decrease in expression of schistosome TGR and CcP in comparison to the untreated group. In contrast, the treatment with praziquantel did not cause significant change in expression of these genes. The results showed more reduction in total worm and female worm count in combined ART-PZQ treated group than in monotherapy treated groups by either ART or PZQ. Moreover, complete disappearance(100%) of tissue eggs was recorded in ART-PZQ treated group with a respective reduction rate of 95.9% and 68.4% in ART- and PZQ-treated groups. Conclusion The current study elucidated for the first time that anti-schistosomal mechanisms of artesunate is mediated via reduction in expression of schistosome TGR and CcP. Linking these findings, addition of artesunate to praziquantel could achieve complete cure outcome in treatment of schistosomiasis.展开更多
Background:Artesunate(ART),a member of the artemisinin family,possesses multi-properties,including antiinflammation,anti-oxidation,and anti-tumor.ART was recently reported to show anti-neovascularization effect on the...Background:Artesunate(ART),a member of the artemisinin family,possesses multi-properties,including antiinflammation,anti-oxidation,and anti-tumor.ART was recently reported to show anti-neovascularization effect on the cornea,iris,and retina.Compared to the expensive anti-VEGF treatment,this versatile,economical treatment option is attractive in the ophthalmic field.The safety and toxicity profile of ART intravitreal application are in utmost need.Methods:In this study,immortalized microglial(IMG)cells were treated with ART to determine the safe concentrations without inducing overt inflammatory reactions.Reverse transcription-polymerase chain reaction analysis was used to detect the cytokine expressions in IMG cells in response to ART stimulation.Various doses of ART were intravitreally injected into the right eyes of C57BL/6 mice.Retinal function was tested by electroretinogram,and retinal ganglion cell(RGC)survival was evaluated by counting Brn3a stained cells in flat-mounted retinas at 7 days after ART injection.Results:ART below 5μM was safe for IMG cells in vitro.Both 2.5 and 5μM ART treatment increased IL-10 gene expression in IMG cells while not changing IL-1β,IL-6,TNF-α,and Arg-1.In the in vivo study,intravitreal injection of ART below 100μM did not cause deterioration in the retinal function and RGC survival of the mouse eyes,while 1 mM ART treatment significantly attenuated both the scotopic and photopic b-wave amplitudes and impaired RGC survival.In addition,treatment with ART of 25,50,and 100μM significantly decreased TNF-αgene expression while ART of 100μM significantly increased IL-10 in the mouse retina.Conclusions:Intravitreal injection of 100μM ART could downregulate TNF-αwhile upregulate IL-10 in the mouse retina without causing retinal functional deterioration and RGC loss.ART might be used as anti-inflammatory agent for retinal disorders.展开更多
基金support by the Establishment of Sino-Austria“Belt and Road”Joint Laboratory on Traditional Chinese Medicine for Severe Infectious Diseases and Joint Research,China(Grant No.:2020YFE0205100)the National Key Research and Development Program of China(Grant Nos.:2020YFA0908000,2022YFC2303600)+9 种基金the Distinguished Expert Project of Sichuan Province Tianfu Scholar(Grant No.:CW202002)the Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine,China(Grant No.:ZYYCXTD-C-202002)the National Natural Science Foundation of China(Grant Nos.:82141001,82274182,82074098,82173914)the China Academy of Chinese Medical Sciences(CACMS)Innovation Fund,China(Grant Nos.:CI2021A05101,CI2021A05104)the Scientific and Technological Innovation Project of China Academy of Chinese Medical Sciences(Grant No.:CI2021B014)the Science and Technology Foundation of Shenzhen,China(Grant No.:JCYJ20210324115800001)the Science and Technology Foundation of Shenzhen,China(Shenzhen Clinical Medical Research Center for Geriatric Diseases),the National Key R&D Program of China Key Projects for International Cooperation on Science,Technology and Innovation(Grant No.:2020YFE0205100)the Fundamental Research Funds for the Central Public Welfare Research Institutes,China(Grant Nos.:ZZ14-YQ-050,ZZ14-YQ-051,ZZ14-YQ-052,ZZ14-FL-002,ZZ14-ND-010,ZZ15-ND-10),Shenzhen Governmental Sustainable Development Fund,China(Grant No.:KCXFZ20201221173612034)Shenzhen key Laboratory of Kidney Diseases,China(Grant No.:ZDSYS201504301616234)Shenzhen Fund for Guangdong Provincial High-level Clinical Key Specialties,China(Grant No.:SZGSP001).
文摘Sepsis is characterized by a severe and life-threatening host immune response to polymicrobial infection accompanied by organ dysfunction.Studies on the therapeutic effect and mechanism of immunomodulatory drugs on the sepsis-induced hyperinflammatory or immunosuppression states of various immune cells remain limited.This study aimed to investigate the protective effects and underlying mechanism of artesunate(ART)on the splenic microenvironment of cecal ligation and puncture-induced sepsis model mice using single-cell RNA sequencing(scRNA-seq)and experimental validations.The scRNA-seq analysis revealed that ART inhibited the activation of pro-inflammatory macrophages recruited during sepsis.ART could restore neutrophils’chemotaxis and immune function in the septic spleen.It inhibited the activation of T regulatory cells but promoted the cytotoxic function of natural killer cells during sepsis.ART also promoted the differentiation and activity of splenic B cells in mice with sepsis.These results indicated that ART could alleviate the inflammatory and/or immunosuppressive states of various immune cells involved in sepsis to balance the immune homeostasis within the host.Overall,this study provided a comprehensive investigation of the regulatory effect of ART on the splenic microenvironment in sepsis,thus contributing to the application of ART as adjunctive therapy for the clinical treatment of sepsis.
基金Financial support was provided by the National Natural Science Foundation of China(grant no.21807024)the Youth Top-notch Talents Supporting Plan of Hebei Province(QNBJ19004)+4 种基金Scientific Research Foundation of Hebei Province for the Returned Overseas Chinese Scholars(C20220508)the Science and Technology Project of Hebei Education Department(no.ZD2021072)the Central Guidance on Local Science and Technology Development Fund of Hebei Province(226Z2601G)Science Fun for Creative Research Groups of Natural Science Foundation of Hebei Province(no.H2020206474)supported by the Postdoctoral Fund of Hebei Medical University.
文摘Tumor microenvironment(TME)with the particular features of severe hypoxia,insufficient endogenous H2O2,and overexpression of glutathione(GSH)markedly reduced the antitumor efficacy of monotherapy.Herein,a TME-responsive multifunctional nanoplatform(Bi2S3@Bi@PDA-HA/Art NRs)was presented for synergistic photothermal therapy(PTT),chemodynamic therapy(CDT),and photodynamic therapy(PDT)to achieve better therapeutic outcomes.The Z-scheme heterostructured bismuth sulfide@bismuth nanorods(Bi2S3@Bi NRs)guaranteed excellent photothermal performance of the nanoplatform.Moreover,its ability to produce O2 and reactive oxygen species(ROS)synchronously could relieve tumor hypoxia and improve PDT outcomes.The densely coated polydopamine/ammonium bicarbonate(PDA/ABC)and hyaluronic acid(HA)layers on the surface of the nanoplatform enhanced the cancer-targeting capacity and induced the acidic TME-triggered in situ“bomb-like”release of Art.The CDT treatment was achieved by activating the released Art through intracellular Fe2+ions in an H2O2-independent manner.Furthermore,decreasing the glutathione peroxidase 4(GPX4)levels by Art could also increase the PDT efficiency of Bi2S3@Bi NRs.Owing to the synergistic effect,this nanoplatform displayed improved antitumor efficacy with minimal toxicity both in vitro and in vivo.Our design sheds light on the application of phototherapy combined with the traditional Chinese medicine monomer-artesunate in treating the hypoxic tumor.
文摘Diabetes is a metabolic disease characterized by abnormally elevated blood glucose levels.Persistent hyperglycemia leads to diabetic nephropathy,diabetic retinopathy,diabetes with periodontal disease and other diabetic complications.These diseases have become the main causes of disability and death in diabetic patients.Artesunate is well known as an antimalarial drug for controlling malaria symptoms.Current studies have shown that artesunate improves diabetes and its complications by protecting islet cells,improving glucose and lipid metabolism,anti-inflammatory and immune regulation.Based on the research status in recent years,this paper focuses on the mechanism of artesunate in diabetes and its complications,to provide a theoretical basis for future diabetes research.
文摘The combination of Artesunate (ART) and Paclitaxel (PTX) in two human prostate cancer (PCa) cell lines (PC-3 and LNCaP) was evaluated to investigate the effects on proliferation, apoptosis and morphological changes. The half maximal inhibitory concentration (IC<sub>50</sub>) values that were observed by ART and PTX on both LNCaP and PC-3 cell lines at 72-and 120-hour exposure were used to assess these effects. Early and late apoptosis was detected in Annexin V-FITC/PI assay revealed a shift in population of cells towards early and mid-apoptosis with ART + PTX than with ART and PTX individually. More effects were observed on LNCaP cell lines at both 72-hour and 120-hour exposure. The results for the Caspase 3/7 activity assay showed shift of viable population in all induced samples compared to control. Morphological changes occurred in both cell lines;this was validated in qualitative assessment when examined under the inverted microscope. These findings indicated that ART + PTX suppressed PCa cell proliferation in a dose- and time-dependent manner.
基金Supported by the National Natural Science Foundation of ChinaNo.81070339+13 种基金the International Science and Technology Cooperation Project of ShanxiNo.2010081068the Key Laboratory Foundation of Cellular Physiology Department of Shanxi Medical School and Provincial Ministry of EducationNo.2010-09the Fund for Returned Students of ShanxiNo.211-091the Fund for Returned Medical Doctors of Changzhi Medical CollegeNo.2010-01Science and Technology Innovation Team Project of Changzhi Medical CollegeNo.CX201409College Student Innovation and Entrepreneurship Training Project of Shanxi ProvinceNo.2014308the US NIH(to Cheng Ji)No.R21AA023952 and No.P30DK48522-21
文摘AIM: To evaluate the effect of artesunate(AS) supplementation on bacterial translocation(BT) and gut microbiota in a rat model of liver cirrhosis. METHODS: Fifty-four male Sprague-Dawley rats were randomly divided into a normal control group(N), a liver cirrhosis group(M) and a liver cirrhosis group intervened with AS(MA). Each group was sampled at 4, 6 and 8 wk. Liver cirrhosis was induced by injection of carbon tetrachloride(CCl4), intragastric administration of 10% ethanol, and feeding a high fat diet. Rats in the MA group were intragastrically administered with AS(25 mg/kg body weight, once daily). Injuries of the liver and intestinal mucosa were assessed by hematoxylineosin or Masson's trichrome staining. Liver index was calculated as a ratio of the organ weight(g) to body weight(g). The gut microbiota was examined by automated ribosomal intergenic-spacer analysis of fecal DNA. BT was assessed by standard microbiological techniques in the blood, mesenteric lymph nodes(MLNs), liver, spleen, and kidney. RESULTS: Compared to group N, the body weight was reduced significantly in groups M and MA due to the development of liver cirrhosis over the period of 8 wk. The body weight was higher in group MA than in group M. The liver indices were significantly elevated at 4, 6 and 8 wk in groups M and MA compared to group N. AS supplementation partially decreased the liver indices in group MA. Marked histopathologic changes in the liver and small intestinal mucosa in group M were observed, which were alleviated in group MA. Levels of pro-inflammatory interleukin-6 and tumor necrosis factor-α were significantly elevated at 8 wk in ileal homogenates in group M compared to group N, which were decreased after AS supplementation in group MA. The dysbiosis of gut microbiota indicated by the mean diversity(Shannon index) and mean similarity(Sorenson index) was severe as the liver cirrhosis developed, and AS supplementation had an apparent intervention effect on the dysbiosis of gut microbiota at 4 wk. The occurrence of BT was increased in the liver of group M compared to that of group N. AS supplementation reduced BT in group MA at 8 wk. BT also occurred in the MLNs, spleen, and kidney, which was reduced by AS supplementation. BT was not detected in the blood in any group.CONCLUSION: Dysbiosis of gut microbiota, injury of intestinal mucosal barrier and BT occurred as liver cirrhosis progressed, which might enhance inflammation and aggravate liver injury. AS may have other nonantimalarial effects that modulate gut microbiota,inhibit BT and alleviate inflammation, resulting in a reduction in CCl4, alcohol and high fat-caused damages to the liver and intestine.
文摘AIM:To study the braking effectiveness of artesunate on transforming growth factor(TGF)-β2 mediated epithelial-mesenchymal transition(EMT)in retinal pigment epithelium(RPE)in vitro.METHODS:The fostered ARPE-19 cells were processed with artesunate alone or combined with the TGF-β2.The CCK-8 examination was utilized to test the cell propagation.Cell migration was detected by scratch as well as the Transwell examination.The EMT characters and activation of PI3K/Akt signal channel were estimated by Western blotting and immunofluorescence.The Western blotting was utilized in order to confirm the vitreous of controls as well as patients with proliferative vitreoretinopathy(PVR)were collected and the levels of PI3K,phospho-PI3K,Akt.RESULTS:Disposal of ARPE-19 cells with artesunate(50-150μmol/L)obviously suppressed their propagation and immigration,which dependent on the concentration and time.Artesunate suppressed the EMT which was induced by TGF-β2 in ARPE-19 cells through sustaining the expression of vimentin andα-SMA through the suppression of PI3K,phospho-PI3K,phospho-Akt and Akt.Levels of PI3K,phospho-PI3K,AKT and phospho-Akt was increased in the vitreous in PVR(P<0.05).CONCLUSION:Such findings indicate that PI3K/Akt signal channel is highly activated in vitreous of PVR.Artesuante is an operative depressor of the propagation,immigration and TGF-β2-mediated EMT of ARPE-19 cells by reduced the expression of PI3K/Akt channel.
基金The project supported by a NMRC grant NMRC/CBRG/0027/2012from the National Medical Research Council of Singapore,with additional support from the Singapore-MIT Alliance for Research and Technology
文摘OBJECTIVE To investigate the genome protective effects of anti-malaria drug,artesunate in an experimental allergic asthma model.METHODS Mice were sensitized on day 0 and 7 and challenged on day 14 with 100μg house dust mite(HDM)via intratracheal administration.Artesunate(30mg·kg-1)was administered intra-peritoneally on day 6,7,8,13,14 and 15.Samples were collected on day 1,3 and 5 post last HDM-challenge for analysis of air way inflammation and DNA damage.Lung sections were immunofluorescence(IF)-stained for DNA double strand breaks(DSBs)markers,γH2AX and 53BP1.Levels of DNA repair proteins Ku70 and Rad51,which are involved in non-homologous end joining(NHEJ)and homologous recombination(HR)DNA DSB repair pathways respectively,were measured.To quantify cell death in asthmatic lung,TUNEL staining was performed.Comet assay,a single cell gel electrophoresis was employed to detect DNA damage induced by HDM in BEAS-2Bhuman bronchial epithelial cell line,in vitro.RESULTS Artesunate treatment significantly reduces immune cells infiltration in BAL fluid of asthmatic mice,collected on day 3 and 5 post-challenge.Importantly,artesuante is able to protect bronchial epithelium from DNA DSBs induced by asthma,as detected by the reduced level of γH2AX and 53BP1 foci formation in the nucleus.This genome protective effect is evident even on day 1 post-challenge,when immune cells infiltration remained high.This indicates that artesunate confers protection on bronchial epithelium in the presence of inflammation.Additionally,artesunate is also able to reduce cell death in asthmatic lung revealed by TUNEL assay and cleaved caspase 3 level.Interestingly,the levels of DNA repair proteins in artesuante-treated asthmatic mice are unchanged as compared to HDM-only mice,suggesting that artesunate treatment does not augment the level of DNA repair proteins.When human bronchial epithelial BEAS-2 Bcells were exposed to HDMin vitro,we observed an increase in the levels of DNA damage.Artesunate(60μmol·L-1)co-incubated with HDM is not able to prevent direct DNA damage induced by the allergen.Together,these studies suggest that the genome protective effect of artesunate in vivo may be attributed to physiological effects(such as its anti-inflammatory effects)rather than serving to directly prevent DNA damage.CONCULSION This study highlights a novel role for artesunate in protecting bronchial epithelial cells from asthma-induced DNA damage.
文摘Introduction: Severe malaria is one of the leading causes of death in Sub-Saharan African countries, and artesunate is recommended as a first-line treatment by the Word Heath Organization (WHO.). Objective: Identify the advantages of artesunate compared with quinine in the treatment of severe malaria in children. Methods and patients: This study was a cross-sectional, descriptive and analytical study focused on children hospitalized for severe malaria in the CNHU who were treated with quinine or artesunate. Findings: The hospital-based frequency rate of severe malaria in pediatric patients was estimated to be 28.3% (n = 848). One hundred five children were treated with artesunate, and 743 were treated with quinine. The mean age of the children was 47 months old. The primary signs of severity were anemia (n = 776), neurological manifestations (n = 309) and hemolysis (n = 137). The average duration of treatment was 1.95 days for artesunate versus 2.45 days for quinine, and the difference was statistically significant (p = 0.001). The average length of stay (ALOS) in the hospital was 5 days for the artesunate group versus 5.75 days for the quinine group, and the difference was statistically significant (p < 0.001). Six of the children who received artesunate died, whereas 24 children who treated with quinine died. The total average cost of healthcare was 50,600 FCFA (77 euros) per child treated with artesunate versus 57,100 FCFA (87 euros) per child treated with quinine. Conclusion: The treatment of severe malaria with artesunate is superior to quinine-based treatment.
文摘Objective:To determine the suppressive and curative activity of aqueous leaf extract of Ageratum conyzoides(A.conyzoides) in combination with chloroquine and artesunate, respectively against Plasmodium berghei infection in mice.Methods:Using malaria(Plasmodium berghei) infected albino mice of both sexes,aqueous extracts of A.conyzoides in combination with chloroquine and artesunate were tested for antimalarial activity,respectively.Four-day suppressive test and Rane’s curative test were carried out.Results:Suppressive tests showed significant dose dependent reduction in parasitemia level produced by the extract-chloroquine and extract-artesunate combinations.Suppressive activities of both extract-drug combinations were greater than the individual drugs alone.Extract-chloroquine(100:5) produced the highest suppressive effect(98%suppression).Curative tests showed absolute survival in two extract-drug combinations.Two extract-drug combinations produced higher curative effects than the individual drugs alone.The highest dose combinations of extract-chloroquine(100:5) and extract-artesunate(100:5) produced absolute parasitemia clearance(cure) in the infected mice. Conclusions:The study indicated that aqueous extract of A.conyzoides had the ability to potentiate the antimalarial activity of chloroquine and artesunate against induced plasmodiasis in mice.It contributes a lot in the malaria endemic and poverty stricken tropics.
基金The Higher Education Research Promotion and National Research University Project of Thailand,Office of the Higher Education Commission,though the Health Cluster(SHePGMS),Khon Kaen University to student,Miss Phornphitcha Pechdee and advisor,Assoc.Prof.Dr.Smarn Tesana for financial support of this work
文摘Objective:To explore larvicidal effects of anthelmintic drugs on Opisthorchis viverrini(O.viverrini) for alternative approach to interrupting its cycle for developing a field-based control program.Methods:The larvicidal activities of albendazole(A1),artesunate(Ar),praziquantel(Pzq) and miltefosine(Mf) on O.viverrini cercariae and mature metacercariae were investigated.Lethal concentrations(LC_(50) and LC_(95)) of these drugs were determined.Mature metacercariae previously exposed to various concentrations of the drugs were administered to hamsters.Worms were harvested 30 d post infection and worm recovery rates calculated.Al,Ar,Pzq and Mf produced morphological degeneration and induced shedding tails of cercariae after 24 h exposure.Results:The LC_(50) and LC_(95) of Al,Ar,Pzq and Mf on cercariae were 0.720 and 1.139,0.350 and 0.861,0.017 and 0.693,and 0.530 and 1.134 ppm,respectively.LC_(50) and LC_(95) of Ar on mature metacercariae were 303.643 and 446.237 ppm and of Mf were 289.711 and 631.781 ppm,respectively but no lethal effect in Pzq-and Al-treated groups(up to 1 ppt).No worms were found in hamsters administered Pzq-treated metacercariae.The adult worms from Al-treated metacercariae were significantly bigger in size compared to the control group(P<0.05).Fecundity and body width were greater in adults from Mf-treated metacercariae compared to the control group(P<0.05).Conclusions:The larvicidal effects of these drugs were high efficacy to O.viverrini cercariae but lesser efficacy to metacercariae.It should be further studied with the eventual aim of developing a field-based control program.
基金research grant(A-059)from All India Institute of Medical Sciences,New Delhi.Artesunate and diclofenac were kind gifts from Arbro Pharmaceuticals Ltd.,New Delhi.
文摘Artesunate, an antimalarial drug, has been shown to inhibit the release of inflammatory mediators in various disease conditions. The present study was carried out to evaluate the anti-edematogenic effect of arte- sunate in the rat paw edema model. Inflammation was induced in the hind paw of rat by sub-plantar injection of 0.1 mL of 0.5% carrageenan and the paw volume was measured up to a fixed mark just before the injection and then after 3 h. The difference in two volumes gave a measure of edema formation. At 3h the level of TNF-α, PGE_(2) and myeloperoxidase were estimated in the inflamed paw tissue. Treatment of rats with single dose of artesunate at 50 and 150 mg/kg produced a dose-dependent inhibition in paw inflammation where a significant reduction in edema volume and mediator release was observed. Our study shows that by inhibiting the release of inflam- matory mediators artesunate affords protection against acute inflammation induced in the rat paw and suggests that it has a potential to be used in the treatment of inflammatory disease conditions.
文摘Effects of amodiaquine, artesunate and artesunate amodiaquine combination on open field novelty-induced behaviors and spatial memory in healthy mice were studied. Forty mice were used in the open field and fifty each in the radial arm maze and Y maze;mice were assigned into four or five groups of ten each, Group A served as control (distilled water), Groups B, C and D received artesunate (4 mg/kg), amodiaquine (10 mg/kg) and artesunate-amodiaquine combination (4 mg/kg and10 mg/kg) respectively, while Group E animals (for the cognition tests) were given scopolamine (2 mg/kg). Drugs and vehicle were administered orally for three days. Results were analysed by one way analysis of variance followed by a posthoc test. Results showed that artesunate and amodiaquine either in combination or administered singly caused a significant increase in open field novelty-induced horizontal locomotion and rearing. Grooming in the open field showed increments in the artesunate alone and artesunate amodiaquine groups while significant reductions in spatial memory were also seen in the cognition models used.
文摘Alzheimer disease is one of the commonest neurological diseases which is characterized by amyloid plaques accumulation in multiple brain regions. This study investigated the potential neuroprotective effect of artesunate on aluminum induced neurotoxicity vs memantine in rats. 40 male albino Wistar rats were divided randomly into 4 groups as follow: Group 1 negative control, group 2 positive control group induced by ammonium chloride, group 3 rats treated by NH4Cl + artesunate solution, group 4 rats treated by NH4Cl + memantine S.C. spatial Memory and Learning were evaluated using Morris Water Maze (MWM) test. Malondialdehyde (MDA) and reduced glutathione (GSH) levels were measured in cerebral cortex tissue homogenate. Tumor necrosis factor-α (TNFα) and interleukin-1 beta (IL-1β) concentrations were measured in rat cerebral cortex tissue homogenate using rat enzyme linked immunosorbent assay (ELISA) kits. Real-time quantitative reverse transcription-polymerase chain reaction (Real-time qRT-PCR) for Caspase-3, Bcl-2 and iNOS gene expression was measured in rat cerebral cortex. Slices from cerebral cortex were studied by histopathological examination. Artesunate significantly decreased MDA level and inhibited iNOS, caspase and upregulated Bcl-2 gene expression in cerebral cortex. ART increased significantly antioxidant level GSH, and decreased significantly TNF-alpha and IL-B levels. It reduced significantly 1ry retention latency, 2ry retention latency and initial acquisition latency. It also improved brain histopathology and decreased amyloid plaque deposition. ART exerted neuroprotective effect through oxidative stress correction and enhancement of antiapoptotic markers in neuronal cells of the cerebral cortex.
文摘Introduction: Artemisinin-based combination therapies are the first-line antimalarial drugs used to treat uncomplicated Plasmodium falciparum malaria in many endemic countries worldwide. In Chad, since the adoption of artemisinin-based combination therapy (ACTs) in its first-line treatment policy for uncomplicated malaria in 2005, Artemether-Lumefantrine and Artesunate-Amodiaquine have been used in many hospitals and health centers. The main objective of this study was to provide the baseline data of Artemether-Lumefantrine and Artesunate-Amodiaquine efficacy in three regions where many people suffered from malaria disease. Material and Methods: The baseline efficacy of two combination therapies was evaluated between January and April 2020 in Mosoro, Mondou and Dourbali Provinces in Chad. A two-arm single cohort study was conducted to assess the clinical efficacy of artesunate-amodiaquine and artemether-lumefantrine for the treatment of 1113 children aged from 6 to 59 months with uncomplicated Falciparum malariae diagnosed by thick blood smear examination, using the World Health Organization validated protocol. Results: On day 3, all patients in both groups had cleared parasitemia, after treatment, the patients presented a higher hemoglobin level in both groups artemether-lumefantrine (10.97 ± 1.39) and artesunate-amodiaquine (11.87 ± 1.81), respectively. On day 28, all patients had adequate clinical and parasitological responses with 99.82% of artesunate-amodiaquine and 99.10% of artemether-lumefantrine. Overall, both drugs were well tolerated at the clinical and biological level, no late parasitological failures have been recorded in artemether-lumefantrine and artesunate-amodiaquine groups, also both forms of Artemisinin-based combination therapy were still effective and safe in the treatment of uncomplicated P. falciparum malaria in Chad.
基金Province Science Fund for Young Scholars (No. QC05C46)Science Foundation from Health Bureau of Heilongjiang Province (No. 2005-47)
文摘Purpose: The objective of this study was to investigate the anti-tumor effects and analyze the mechanism of artesunate(ART) action on breast cancer in vivo using tumor transplanted nude mice.Methods: The human breast tumor cell line MCF-7 was transplanted into nude mice, and the animals were treated with various doses of ART alone or in combination with cyclophosphamide(CTX) or normal saline(NS). The tumor inhibitory effects were observed and compared, and the ultrastructural morphology of the transplanted tumor cells was observed by electron microscopy. The apoptosis rates and cell cycle status were detected by flow cytometry(FCM). The expression of apoptosis-related proteins p53, Bcl-2, Bax and Caspase-3 were detected by immunohistochemistry and IGF-IR was detected by western blot. The expression correlation for these proteins was also analyzed.Results: The tumor inhibition rates in the low dose ART group, high dose ART group, CTX group and combined drug therapy group were(24.39±10.20)%,(40.24±7.02)%,(57.01±5.84)% and(68.29±5.1)%, respectively. The cell cycle was arrested in phase G0/G1 after treatment with ART. The expression of Bcl-2 was significantly reduced, and the expression levels of Bax and Caspase-3 were significantly increased in the ART group compared to the negative control saline group. There was no significant difference detected in p53 expression. The Bcl-2 level was negatively related to Bax and Caspase-3. The western blotting results showed IGF-IR downregulation.Conclusions: ART inhibits the growth of MCF-7 breast tumor cell xenografts in nude mice. The antitumor mechanism of ART for human breast carcinoma in nude mice might be correlated with the alteration of apoptosis related protein expression, which may further induce apoptosis and inhibit cell proliferation.
文摘Objective To investigate the possible effect of artesunate(ART) on schistosome thioredoxin glutathione reductase(TGR) and cytochrome c peroxidase(CcP) in Schistosoma mansoni-infected mice. Methods A total of 200 laboratory bred male Swiss albino mice were divided into 4 groups(50 mice in each group). Group I: infected untreated group(Control group) received a vehicle of 1% sodium carbonyl methylcellulose(CMC-Na); Group II: infected then treated with artesunate; Group III: infected then treated with praziquantel, and group IV: infected then treated with artesunate then praziquantel. Adult S. mansoni worms were collected by Animal Perfusion Method, tissue egg counted, TGR, and CcP mRNA Expression were estimated of in S. mansoni adult worms by semi-quantitative rt-PCR. Results Semi-quantitative rt-PCR values revealed that treatment with artesunate caused significant decrease in expression of schistosome TGR and CcP in comparison to the untreated group. In contrast, the treatment with praziquantel did not cause significant change in expression of these genes. The results showed more reduction in total worm and female worm count in combined ART-PZQ treated group than in monotherapy treated groups by either ART or PZQ. Moreover, complete disappearance(100%) of tissue eggs was recorded in ART-PZQ treated group with a respective reduction rate of 95.9% and 68.4% in ART- and PZQ-treated groups. Conclusion The current study elucidated for the first time that anti-schistosomal mechanisms of artesunate is mediated via reduction in expression of schistosome TGR and CcP. Linking these findings, addition of artesunate to praziquantel could achieve complete cure outcome in treatment of schistosomiasis.
基金supported by Midstream Research Programme for Universities,Hong Kong to Kin Chiu(Project No:MRP-092–17X).
文摘Background:Artesunate(ART),a member of the artemisinin family,possesses multi-properties,including antiinflammation,anti-oxidation,and anti-tumor.ART was recently reported to show anti-neovascularization effect on the cornea,iris,and retina.Compared to the expensive anti-VEGF treatment,this versatile,economical treatment option is attractive in the ophthalmic field.The safety and toxicity profile of ART intravitreal application are in utmost need.Methods:In this study,immortalized microglial(IMG)cells were treated with ART to determine the safe concentrations without inducing overt inflammatory reactions.Reverse transcription-polymerase chain reaction analysis was used to detect the cytokine expressions in IMG cells in response to ART stimulation.Various doses of ART were intravitreally injected into the right eyes of C57BL/6 mice.Retinal function was tested by electroretinogram,and retinal ganglion cell(RGC)survival was evaluated by counting Brn3a stained cells in flat-mounted retinas at 7 days after ART injection.Results:ART below 5μM was safe for IMG cells in vitro.Both 2.5 and 5μM ART treatment increased IL-10 gene expression in IMG cells while not changing IL-1β,IL-6,TNF-α,and Arg-1.In the in vivo study,intravitreal injection of ART below 100μM did not cause deterioration in the retinal function and RGC survival of the mouse eyes,while 1 mM ART treatment significantly attenuated both the scotopic and photopic b-wave amplitudes and impaired RGC survival.In addition,treatment with ART of 25,50,and 100μM significantly decreased TNF-αgene expression while ART of 100μM significantly increased IL-10 in the mouse retina.Conclusions:Intravitreal injection of 100μM ART could downregulate TNF-αwhile upregulate IL-10 in the mouse retina without causing retinal functional deterioration and RGC loss.ART might be used as anti-inflammatory agent for retinal disorders.
