Sequential analysis of erythrocyte aggregation in P. falciparum malaria with and without ASAQ therapy by optical signal and image analysis

The aggregation of erythrocytes is an important mechanism for blood flow through the cardiovascular system. In malaria, this is complicated by infection caused by P. falciparum and is further complicated by the severity of parasitemia. Hence analysis of this micro-mechanism is essential to know the changes in blood not only in diseased conditions but also after artemisinin combination therapy (ASAQ) to alleviate suffering. For analysis purposes, aggregation of erythrocytes was determined by LED laser aggregometer, represented in terms of various parameters related to the changes in laser transmitted intensity. Formed aggregates are further analyzed by imaging and image-processing methods. For this study blood samples from young adults (18 – 40 years old) infected with P. falciparum (n= 80), without any other serious illness, were performed. These samples were selected based on the severity of parasitemia, and were divided into low (LP), medium1 (MP1), medium 2 (MP2), and high (HP) parasitemia. For three days, the selected individuals were treated with artemisinin-based combination therapy ASAQ (Artesunate 4 mg/kg and amodiaquine 10 mg base/ kg once a day). Healthy subjects (n=20) without any history of the disease were selected as a control group. The results, as obtained by various parameters, show a significant elevation of aggregation of erythrocytes (P< 0.05) in P. falciparum malaria with the increase of parasitemia level. There was a decrease in the aggregation after treatment on day four tending towards normal. Thus the current study shows the potential beneficial role of ASAQ on erythrocytes aggregation, which may contribute to reducing the harmful effects on various organs in P. falciparum-infected blood.

Molecular detection of drug-resistant Plasmodium falciparum mutants in Assam

Background & objectives: The spread of drug-resistant Plasmodium falciparum ( Pf) poses a serious threat to the control and elimination of malaria. The objective of this study was to detect the molecular biomarkers of antimalarial drug resistance in Pf in patients visiting a tertiary care hospital in Assam. Methods: Malaria was first detected in fever cases using microscopy and a rapid diagnostic test (RDT), and then confirmed using PCR. Pf chloroquine resistance transporter (Pfcrt), Pf multidrug resistance-1 (Pfmdr-1), and single-nucleotide polymorphisms linked to delayed parasite clearance after treatment with artemisinin MAL 10-688956 and MAL 13-1718319 and Kelch-13 propeller (PfK-13) genes were evaluated by PCR-restriction fragment length polymorphism (RFLP). Results: Sixty nine cases of malaria were found among 300 cases of fever. Of these, 54 were positive for Pf, 47 of which were confirmed by PCR. Pfcrt-K76T mutation was seen in 96.6 per cent and Pfmdr1-N86Y mutation in 84.2 per cent of cases. Mutation was not detected in MAL10 and MAL13 genes. Sequence analysis of Kelch-13 gene showed the presence of a novel mutation at amino acid position 675. Statistically, no significant association was found between the molecular biomarkers and demographic profile, clinical presentation and outcome of the cases. Interpretation & conclusions: Molecular surveillance is essential to assess the therapeutic efficacy of the drugs against circulating Pf isolates in Assam which are found to be highly resistant to CQ. The role of the new mutation found in the Kelch-13 gene in the development of artemisinin resistance in Assam needs to be thoroughly monitored in future research.

Artemisinin drug resistance and monitoring: a narrative review

Artemisinin drug resistance is one of the major reasons for malaria treatment failures in the sub-Saharan African countries where artemisinin-based combination therapy (ACT) is the first-line treatment for uncomplicated malaria. The occurrence of single nucleotide polymorphisms (SNPs) is found to correlate with antimalarial drug resistance. With artemisinin, the SNPs occurs at the Kelch 13-propeller gene locus on chromosome 13. The artemisinin drug resistance surveillance strategy involves continuous monitoring of Kelch 13-propeller biomarker to detect emergence of mutations which could herald drug resistance in the region. In this narrative review paper, we examined existing literature to bridge the knowledge gap and accentuate the importance of routine surveillance for artemisinin resistance in sub-Saharan Africa. We conducted our search on PubMed database and Google Scholar to identify peer-reviewed articles, reports, and abstracts on artemisinin drug resistance using the following keywords; 'artemisinin drug resistance', 'antimalarial drug resistance', 'artemisinin-based combination therapy', 'Kelch 13-propeller', 'K13- propeller gene', and 'K13 molecular marker'. The review provided pertinent information on artemisinin derivatives, artemisinin-based combination therapy, molecular action of artemisinin, definition of artemisinin resistance, genetic basis of artemisinin drug resistance and discovery of Kelch 13, and the importance of artemisinin resistance surveillance. Molecular surveillance can provide healthcare policy makers a forecast of impending threats to malaria treatment. This is more so when drugs are in combination therapy, for instance, molecular surveillance can give a hint that one drug is failing despite the fact that in combination, it is still apparently clinically effective.

Artemisinin drug resistance and monitoring: a narrative review

Artemisinin drug resistance is one of the major reasons for malaria treatment failures in the sub-Saharan African countries where artemisinin-based combination therapy (ACT) is the first-line treatment for uncomplicated malaria. The occurrence of single nucleotide polymorphisms (SNPs) is found to correlate with antimalarial drug resistance. With artemisinin, the SNPs occurs at the Kelch 13-propeller gene locus on chromosome 13. The artemisinin drug resistance surveillance strategy involves continuous monitoring of Kelch 13-propeller biomarker to detect emergence of mutations which could herald drug resistance in the region. In this narrative review paper, we examined existing literature to bridge the knowledge gap and accentuate the importance of routine surveillance for artemisinin resistance in sub-Saharan Africa. We conducted our search on PubMed database and Google Scholar to identify peer-reviewed articles, reports, and abstracts on artemisinin drug resistance using the following keywords; 'artemisinin drug resistance', 'antimalarial drug resistance', 'artemisinin-based combination therapy', 'Kelch 13-propeller', 'K13- propeller gene', and 'K13 molecular marker'. The review provided pertinent information on artemisinin derivatives, artemisinin-based combination therapy, molecular action of artemisinin, definition of artemisinin resistance, genetic basis of artemisinin drug resistance and discovery of Kelch 13, and the importance of artemisinin resistance surveillance. Molecular surveillance can provide healthcare policy makers a forecast of impending threats to malaria treatment. This is more so when drugs are in combination therapy, for instance, molecular surveillance can give a hint that one drug is failing despite the fact that in combination, it is still apparently clinically effective.

La résistance aux médicaments à base d'artémisinine est l'une des principales raisons des échecs du traitement du paludisme dans les pays d'Afrique subsaharienne où la polythérapie à base d'artémisinine (ACT) est le traitement de première intention du paludisme simple. L'apparition de polymorphismes mononucléotidiques (SNP) est corrélée à la résistance aux médicaments antipaludiques. Avec l'artémisinine, les SNP se produisent au locus du gène Kelch 13- propeller sur le chromosome 13. La stratégie de surveillance de la résistance aux médicaments à base d'artémisinine implique une surveillance continue du biomarqueur Kelch 13-propeller pour détecter l'émergence de mutations qui pourraient annoncer une résistance aux médicaments dans la région. Dans cet article de revue narrative, nous avons examiné la littérature existante pour combler le manque de connaissances et accentuer l'importance de la surveillance de routine de la résistance à l'artémisinine en Afrique subsaharienne. Nous avons effectué notre recherche sur la base de données PubMed et Google Scholar pour identifier des articles, des rapports et des résumés évalués par des pairs sur la résistance aux médicaments à base d'artémisinine en utilisant les mots-clés suivants; «résistance aux médicaments à base d'artémisinine¼, «résistance aux médicaments antipaludiques¼, «thérapie combinée à base d'artémisinine¼, «Kelch 13-propeller¼, «gène K13-propeller¼ et «marqueur moléculaire K13¼. L'examen a fourni des informations pertinentes sur les dérivés de l'artémisinine, la polythérapie à base d'artémisinine, l'action moléculaire de l'artémisinine, la définition de la résistance à l'artémisinine, la base génétique de la résistance aux médicaments à base d'artémisinine et la découverte de Kelch 13, ainsi que l'importance de la surveillance de la résistance à l'artémisinine. La surveillance moléculaire peut fournir aux responsables des politiques de santé une prévision des menaces imminentes pour le traitement du paludisme. C'est d'autant plus vrai lorsque les médicaments sont en thérapie combinée, par exemple, la surveillance moléculaire peut donner un indice qu'un médicament échoue malgré le fait qu'en combinaison, il est toujours apparemment cliniquement efficace.

The stereoselective synthesis of privileged epimer of C-10 carba artemisinins and the effect of substituted groups with different acid-base properties on the antimalarial activity / 药学学报

Artemisinin is a sesquiterpene lactone natural product that contains an endoperoxide bond. Artemisinin has various biological activities including antimalarial, anti-tumor, antiviral and anti-fibrotic activity. Owing to the poor pharmacokinetic properties of artemisinin, its derivatives are currently used in clinic and frequently reported in literature. Although numerous derivatives of artemisinin have been reported, no study has been carried out yet to study the effect of substituted groups with different acid-base property on the antimalarial activity. Among these derivatives, the C-10 carbon artemisinin derivatives are often reported, and their corresponding 10β epimer show much better antimalarial activity than 10α epimer with large-sized substitute. However, there is currently no stereoselective synthesis to efficiently prepare the privileged 10β epimer of C-10 carba artemisinin. To address these two scientific questions, we herein first report an optimized method to stereoselectively synthesize the 10β epimer of C-10 carba artemisinin (98∶2 d.r.). Second, we employed the optimized method to synthesize a series of C-10 carba artemisinin derivatives with different acid-base properties. The antimalarial examination indicated that those derivatives with neutral groups or basic group of short chain showed similar antimalarial activity as dihydroartemisinin (DHA). The acidic group could dramatically decrease the antimalarial effect and was more than 22-fold less effective than DHA or the neutral ones. This study will shed light on the development of new generation of artemisinin derivatives with potent activity.

Exploration on the potential therapeutic mechanism of artemisinin in polycystic ovary syndrome based on network pharmacology and molecular docking technology / 药学实践杂志

Objective To explore the potential mechanism of artemisinin in the treatment of polycystic ovary syndrome (PCOS) by network pharmacology and molecular docking technology. Methods The corresponding targets of natural product artemisinin were obtained from PubChem, Swiss Target Prediction and PharmMapper databases, targets related to PCOS were obtained through GeneCards and DisGeNET databases; the intersection target genes of Artemisinin and PCOS were screened by Draw Venn diagram. Then the protein-protein interaction network (PPI) was constructed according to the intersection target genes through the STRING Database, and the core targets were screened by Cytoscape. Besides, gene ontology (GO) function and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis was performed by DAVID Database, and finally the data were analyzed visually by the online platform. Molecular docking of artemisinin and core targets were performed by Chemdraw, Pymol, Auto Dock Tools and RCSB PDB database. Results A total of 229 targets of artemisinin and 1292 targets of PCOS were screened out, 90 overlapping targets were obtained by Draw Venn diagram, and 5 potential core targets, AKT1, ESR1, MMP9, PPARG, MMP2, were mainly act on PI3K Akt, MAPK, RAS, endocrine resistance and other signal pathways. Molecular docking results showed that there were molecular binding sites between artemisinin and core targets. Conclusion It is preliminarily analyzed that artemisinin may play a therapeutic role in PCOS through multiple targets and mechanisms.

Distribution of gene mutation sites affecting artemisinin metabolism in the Kazak population in Xinjiang / 中国热带医学

@#Abstract: Objective　To detect the distribution of CYP2A6∗2, CYP2A6∗10, CYP2A6∗17, CYP2B6∗4, CYP2B6∗6, and CYP2B6∗18 loci affecting the metabolism of artemisinins in Kazak population in Xinjiang. To explore the pharmacogenetic background of the Kazak population in Xinjiang for artemisinin drugs and provide clinical decision support for the treatment and prevention of malaria based on artemisinin drugs. Methods　Six SNPs including CYP2A6∗2, CYP2A6∗10, CYP2A6∗17, CYP2B6∗4, CYP2B6∗6, and CYP2B6∗18 were selected for the sequencing experiment. 330 whole blood samples were collected from the Kazak population in Xinjiang. After extracting the whole blood DNA genome, multiplex PCR and high-throughput sequencing were used for genotyping. The allele frequencies were analyzed using the Hardy-Weinberg equilibrium. Results　In this study all SNPs follow the Hardy-Weinberg equilibrium (P>0.05), there was no significant difference in the distribution of SNPs between different genders (P>0.05). The number of successfully sequenced samples of CYP2A6∗2, CYP2A6∗10, CYP2A6∗17, CYP2B6∗4, CYP2B6∗6, and CYP2B6∗18 were 326, 319, 328, 318, 322 and 328 respectively. The frequencies of variant alleles of CYP2A6∗2, CYP2A6∗10, CYP2A6∗17, CYP2B6∗4, CYP2B6∗6, and CYP2B6∗18 in Kazak population are: 0.61%, 0%, 0%, 30.97%, 22.98%, 0%. Conclusions　Mutation alleles affecting the metabolism of artemisinins exist in the Kazak population in Xinjiang. When using artemisinins, the relationship between the drug effect and individual pharmacogenetic background should be further explored.

Research progress of artemisinin and its derivatives in prevention and treatment of cardiovascular diseases / 中国药房

Artemisinin is a sesquiterpene lactone containing a peroxide group isolated from the plant Artemisia annua. It has antimalarial activity and is effective for the treatment of malaria. With the deepening of research on artemisinin， the pharmacological effects of artemisinin and its derivatives in other systems have gradually become a research hotspot. This article reviews the research progress of artemisinin and its derivatives in the prevention and treatment of cardiovascular diseases. Artemisinin and its derivatives in the prevention and treatment of cardiovascular disease have shown anti-atherosclerosis， lipid- lowering， inhibition of vascular remodeling， reducing vascular pressure， improving ventricular remodeling， anti-arrhythmia， protection of vascular endothelium， prevention and treatment of diabetic cardiovascular complications and protection of myocardial cells and other pharmacological effects. It provides a new treatment strategy for common cardiovascular diseases such as hypertension， arrhythmia， coronary heart disease complications after stent implantation， hyperlipidemia， etc. However， there are few studies on the antiplatelet aggregation and antithrombotic effects of artemisinin and its derivatives， the molecular mechanisms behind many pharmacological effects have not yet been clarified， and there is little clinical application. A large number of basic studies and clinical trials are still needed to answer these questions.

Effect of a Novel Dihydroartemisinin Dimer Containing Nitrogen Atoms SM 1044 on Apoptosis of Human Leukemia Cell Line NB4-R1 / 中国实验血液学杂志

OBJECTIVE@#To investigate the effect of a water-soluble novel dihydroartemisinin dimer containing nitrogen atoms SM 1044 on the apoptosis of all-trans retinoic acid (ATRA) resistant acute promyelocytic leukemia (APL) NB4-R1 cells and its potential mechanism.@*METHODS@#The effects of SM 1044 on cell apoptosis, mitochondrial transmembrane potential, and the level of reactive oxygen species (ROS) were assessed by flow cytometry. Expressions of apoptosis-related proteins were determined by Western blot. The effects of SM 1044 on MAPK (ERK, JNK) signaling pathway, PML/RARα fusion protein, and expressions of apoptosis-related proteins were detected by Western blot.@*RESULTS@#SM 1044 could significantly induce apoptosis and the loss of mitochondrial transmembrane potential in NB4-R1 cells, and activate apoptosis-related proteins caspase-3, caspase-8, caspase-9 and poly (ADP-ribose) polymerase (PARP). SM 1044 could also induce NB4-R1 cells to produce ROS. Western blot showed that SM 1044 activated the phosphorylation of MAPK (ERK, JNK) signaling pathway and down-regulated the expression of PML/RARα fusion protein.@*CONCLUSION@#SM 1044 can induce apoptosis of ATRA resistant APL NB4-R1 cells, which may be related to ROS/ERK and ROS/JNK signaling pathway, and can also induce by down-regulating PML/RARα fusion protein.

Microbial transformation of artemisinin and its derivatives / 中国中药杂志

Microbial transformation is an efficient enzymatic approach for the structural modification of exogenous compounds to obtain derivatives. Compared with traditional chemical synthesis, the microbial transformation has in fact the undoubtable advantages of strong region-and stereo-selectivity, and a low environmental and economic impact on the production process, which can achieve the reactions challenging to chemical synthesis. Because microbes are equipped with a broad-spectrum of enzymes and therefore can metabolize various substrates, they are not only a significant route for obtaining novel active derivatives, but also an effective tool for mimicking mammal metabolism in vitro. Artemisinin, a sesquiterpene with a peroxy-bridged structure serving as the main active functional group, is a famous antimalarial agent discovered from Artemisia annua L. Some sesquiterpenoids, such as dihydroartemisinin, artemether, and arteether, have been developed on the basis of artemisinin, which have been successfully marketed and become the first-line antimalarial drugs recommended by WHO. As revealed by pharmacological studies, artemisinin and its derivatives have exhibited extensive biological activities, including antimalarial, antitumor, antiviral, anti-inflammatory, and immunomodulatory. As an efficient approach for structural modification, microbial transformation of artemisinin and its derivatives is an increasingly popular strategy that attracts considerable attention recently, and numerous novel derivatives have been discovered. Herein, this paper reviewed the microbial transformation of artemisinin and its artemisinin, including microbial strains, culture conditions, product isolation and yield, and biological activities, and summarized the advances in microbial transformation in obtaining active derivatives of artemisinin and the simulation of in vivo metabolism of drugs.

Eficacia de la artemisina en modelos murinos de leishmaniasis cutánea experimental causada por Leishmania amazonensis / Artemisine efficacy in murine models of experimental cutaneous leishmaniasis caused by Leishmania amazonensis

Los limitados tratamientos disponibles para enfrentar la leishmaniasis requieren el desarrollo de investigaciones para buscar nuevos agentes terapéuticos. Una estrategia recomendada es el reposicionamiento farmacológico, en el que la artemisina figura como un posible candidato. El objetivo de este estudio es evaluar las potencialidades de la artemisina en dos modelos murinos de leishmaniasis cutánea experimental. Para ello, se emplearon ratones BALB/c (susceptibles) y C57BL/6 (resistentes) infectados con Leishmania amazonensis. El tratamiento se realizó por vía oral o intralesional con cinco dosis de artemisina a 30 mg/kg cada 4 días. Se determinó el comportamiento del peso, la evolución del tamaño de la lesión y la carga parasitaria. En ambos modelos animales se observó que el tratamiento con artemisina (oral e intralesional) disminuyó el tamaño de la lesión y la carga parasitaria con respecto a los grupos infectados sin tratamiento (p 0,05). Los ratones C57BL/6 tratados por vía oral fueron los únicos capaces de controlar las lesiones hasta el final del experimento. Se demuestra la eficacia in vivo de la artemisina en dos modelos de leishmaniasis cutánea inducida por L. amazonensis y se destaca la administración por vía oral en el control de la enfermedad. Se sugiere el futuro desarrollo de este fármaco para el tratamiento de la leishmaniasis cutánea.

The limited treatments available for leishmaniasis require the development of research for new therapeutic agents. One recommended strategy is the pharmacological repositioning, where artemisinin stands out as a possible candidate. The aim of this study is to evaluate the potential of artemisinin in two murine models of experimental cutaneous leishmaniasis. For this purpose, BALB/c (susceptible) and C57BL/6 (resistant) mice infected with Leishmania amazonensis were used. Oral or intralesional treatment was performed with five doses of artemisinin at 30 mg/kg every four days. Weight behavior, evolution of lesion size, and parasitic load were determined. In both animal models it was observed that treatment with artemisinin (oral and intralesional) decreased lesion size and parasitic load with respect to the untreated infected groups (p 0.05). Orally treated C57BL/6 mice were the only ones able to control lesions until the end of the experiment. The in vivo efficacy of artemisinin in two models of cutaneous leishmaniasis induced by L. amazonensis is demonstrated and oral administration is highlighted in the control of the disease. Further development of this drug for the treatment of cutaneous leishmaniasis is suggested.

Comparative, observational study of the use of artesunate injections along with standard-of-care treatment versus only standard-of-care treatment in moderate and severe acute respiratory distress syndrome cases of COVID-19-positive infections

Introduction: COVID-19 is a type of coronavirus disease belonging to the family Coronaviridae. In late December 2019, this virus emerged from Wuhan, Hubei province, China, and resulted in an outbreak in China and expanded globally. In India, the mortality rate today was 521,691 till the date-time of writing this article. Several therapeutic agents have been evaluated for the treatment of COVID-19. Materials and Methods: This was a hospital-based comparative, observational study of the use of artesunate injections with standard-of-care (SOC) treatment (group A) versus only SOC (group B) treatment in moderate- to-severe cases of COVID-19 acute respiratory distress syndrome (ARDS) patients, on a total of 130 patients (comparative group of 65 patients each). The study was done on hospitalized COVID-19-positive moderate and severe cases of ARDS from October 2020 to June 2021 at MGM Hospital and Research Centre, CBD Belapur, Navi Mumbai, Maharashtra, India. Results: One hundred and thirty patients were divided into two groups of 65 each; group A was compared with group B; group A received SOC with artesunate injections and group B received only SOC treatment. The mean age of patients in group A was 57.3 ± 12.5 years (standard deviation [SD]: 54.2–60.3) and in group B was 55.8 ± 12.5 years (SD: 52.8–58.9). Diabetes mellitus was the most comorbid condition. The inflammatory markers, respiratory rate, and SpO2 improved in group A as compared to group B. The proportion of patients progressing to noninvasive and invasive ventilation was more in group B as compared to group A (P < 0.05). About 93.8% of patients (61 patients) recovered in group A compared with 72.3% of patients (47 patients) who recovered in group B. The overall death in group A was 6.2% (four patients) and 27.7% (18 patients) in group B (P < 0.05), indicating the proportion of dead patients is significantly more where only SOC treatment was given. Conclusions: Artesunate injection administration accelerated recovery in our patients with moderate and severe COVID-19 disease by controlling hyperimmune response. The clinical improvement was seen by decreased levels of inflammatory markers, reduced respiratory rate, and improved oxygen saturation and showed significant survival in group A compared with group B. Artesunate injections were given 2 mg/kg body weight diluted in 1 mL 5% sodium bicarbonate solution as a bolus followed by 1 mg/kg body weight after 6 h and 2 mg/kg body weight with 1 mL sodium bicarbonate solution for next 2 days at an interval of 24 h. Patients tolerated the injections well and recovery improved, so artesunate can be considered a therapeutic option in moderate and severe cases of COVID-19 ARDS.

The current use of the artemisinin-based combination therapies in adult patients at a tertiary hospital, South-South Nigeria

Objective:The antimalarial preferences, tolerability, and cost of the Artemisinin-based combination therapies (ACTs) among adult patients and caregivers are largely understudied despite being the recommendedtreatment for Plasmodium falciparum.We, therefore, evaluated antimalarial preferences, tolerability, and cost of the ACTs among adult patients attending the University of Benin Teaching Hospital, Nigeria. Methods:This was a cross-sectional study conducted among adult patients and their caregivers atthe University of Benin Teaching Hospital, Nigeria,using a semi-structured questionnaire. Their preferred antimalarial medication, previous use of antimalarial monotherapies, current ACT use; cost considerations, and adverse effects profile were sought.Result:Six hundred respondents were recruited with a mean age of 41.4±16.3years and M/F ratio of 1.4. The majority (88.0%), reported that they had between 1-5 episodes of malaria fever in a year. Only 28.2% received doctors' prescriptions while 85.8% purchased their antimalarial medications from a pharmacy. Sixty percent of the respondents used at least one ACT; mainly Artemether-Lumefantrine (AL) 312(52.0%). Only 9.3% reported previous adverse effects with the ACTs with 4.0% of respondents discontinuing their medications. The mean (SD) cost of purchasing ACTs was 1,516.47±760.3 (3.65 USD) Naira.Conclusion: This study showed adult patients' preference for the ACTs, especially Artemether-Lumefantrine despite some inclination towards antimalarial monotherapies and parenteral route. There was also a high rate of use of malaria presumptive treatment, but only a few reported adverse effects. There is a need to make ACTs affordable because the cost is still presently high for most Nigerians.

Discovery and repurposing of artemisinin / 医学前沿

Malaria is an ancient infectious disease that threatens millions of lives globally even today. The discovery of artemisinin, inspired by traditional Chinese medicine (TCM), has brought in a paradigm shift and been recognized as the "best hope for the treatment of malaria" by World Health Organization. With its high potency and low toxicity, the wide use of artemisinin effectively treats the otherwise drug-resistant parasites and helps many countries, including China, to eventually eradicate malaria. Here, we will first review the initial discovery of artemisinin, an extraordinary journey that was in stark contrast with many drugs in western medicine. We will then discuss how artemisinin and its derivatives could be repurposed to treat cancer, inflammation, immunoregulation-related diseases, and COVID-19. Finally, we will discuss the implications of the "artemisinin story" and how that can better guide the development of TCM today. We believe that artemisinin is just a starting point and TCM will play an even bigger role in healthcare in the 21st century.

Sustainable development roadmap of Chinese antimalarial products / 中国血吸虫病防治杂志

As the first country that has been certified malaria-free in the WHO Western Pacific Region for more than 3 decades, China should share its successful experiences of malaria control and provide globally recognized anti-malaria products by making full uses of its advantages in provision and production capacity of artemisinin raw materials, to fill the gaps of international demands for mosquito nets, rapid diagnostic reagents and antimalarial compounds. Increasing the investment of research and development of antimalarial products, building overseas bases for artemisinin raw material production, establishing international regulatory authority and promoting the local production of antimalarial products are needed to further promote the internationalization of Chinese antimalarial products, so as to achieve the equity and accessibility of Chinese antimalarial products in highburden regions for malaria.

TiO2 nanoparticles and salinity stress in relation to artemisinin production and ADS and DBR2 expression in Artemisia absinthium L / Nanopartículas de TiO2 e estresse de salinidade em relação à produção de artemisinina e expressão de ADS e DBR2 em Artemisia absinthium L

Artemisia absinthium L. is an important herb that is widely cultivated in different parts of the world for its medicinal properties. The present study evaluated the effects of four concentrations of nanoparticles treatment (0, 10, 20 and 30 mg L-1) and NaCl salinity stress (0, 50, 100 and 150 mM NaCl) and their interactions with respect to the expression of two key genes, i.e. DBR2 and ADS, in the biosynthesis pathway of artemisinin in A. absinthium. Total RNA was extracted and a relative gene expression analysis was carried out using Real-Time PCR. The amount of artemisinin was also determined by HPLC. All the experiments were performed as factorial in a completely randomized design in three replications. The results revealed that salinity stress and nanoparticles treatment and their interaction affected the expressions of these genes significantly. The highest levels of ADS gene expression were observed in the 30 mg L-1 nanoparticles­treated plants in the presence of 150 mM salinity stress and the lowest levels in the 10 mg L-1 nanoparticles­treated plants under 50 mM salinity stress. The maximum DBR2 gene expression was recorded in the 10 mg L-1 nanoparticles­treated plants in the absence of salinity stress and the minimum expression in the 100 mM salinity-stressed plants in the absence of nanoparticles treatment. Moreover, the smallest amounts of artemisinin were observed in the 150 mM salinity-stressed plants in the absence of nanoparticles and the highest amounts in the 30 mg L-1 nanoparticles­treated plants. The maximum amounts of artemisinin and ADS gene expression were reported from the plants in the same nanoparticles treatment and salinity stress conditions. In this regard, the amount of artemisinin was decreased by half in the plants containing the highest DBR2 gene expression. Meanwhile, no significant correlation was observed between these gene expressions and the artemisinin amount in the other nanoparticles­treated plants under different levels of salinity stress. The biosynthetic pathway of secondary metabolites appears to be very complex and dose not directly dependent on these gene expressions.

Artemisia absinthium L. é uma erva importante que é amplamente cultivada em diferentes partes do mundo por suas propriedades medicinais. O presente estudo avaliou os efeitos de quatro concentrações de tratamento com nanopartículas (0, 10, 20 e 30 mg L-1) e estresse de salinidade com NaCl (0, 50, 100 e 150 mM NaCl) e suas interações com relação à expressão de dois genes-chave, isto é, DBR2 e ADS, na via de biossíntese da artemisinina em A. absinthium. O RNA total foi extraído, e uma análise de expressão gênica relativa foi realizada usando PCR em tempo real. A quantidade de artemisinina também foi determinada por HPLC. Todos os experimentos foram realizados como fatorial, em delineamento inteiramente casualizado, em três repetições. Os resultados revelaram que o estresse por salinidade e o tratamento com nanopartículas e sua interação afetaram significativamente as expressões desses genes. Os níveis mais altos de expressão do gene ADS foram observados nas plantas tratadas com nanopartículas de 30 mg L-1 na presença de estresse de salinidade de 150 mM, e os níveis mais baixos, nas plantas tratadas com nanopartículas de 10 mg L-1 com estresse de salinidade de 50 mM. A expressão máxima do gene DBR2 foi registrada nas plantas tratadas com nanopartículas de 10 mg L-1 na ausência de estresse de salinidade, e a expressão mínima, nas plantas estressadas com salinidade de 100 mM na ausência de tratamento com nanopartículas. Além disso, as menores quantidades de artemisinina foram observadas nas plantas com estresse de salinidade de 150 mM na ausência de nanopartículas, e as maiores quantidades, nas plantas tratadas com nanopartículas de 30 mg L-1. As quantidades máximas de expressão de genes de artemisinina e ADS foram relatadas a partir das plantas no mesmo tratamento com nanopartículas e condições de estresse de salinidade. A esse respeito, a quantidade de artemisinina diminuiu pela metade nas plantas que contêm a expressão gênica DBR2 mais alta. Enquanto isso, nenhuma correlação significativa foi observada entre essas expressões gênicas e a quantidade de artemisinina nas outras plantas tratadas com nanopartículas sob diferentes níveis de estresse de salinidade. A via biossintética dos metabólitos secundários parece ser muito complexa e não depende diretamente dessas expressões gênicas.

Analysis of the clinical treatment effect of 116 imported falciparum malaria cases in Wuhan City / 公共卫生与预防医学

Objective To analyze and evaluate the clinical characteristics of imported falciparum malaria cases and the antimalarial effect of artemisinin-based drugs, to promote rational and standardized drug use, and to improve the clinical cure rate of falciparum malaria. Methods A total of 116 imported cases of falciparum malaria admitted to the provincial malaria designated hospital in Wuhan were collected, and the clinical characteristics of the patients and use of artemisinin, and the therapeutic effects of the artemisinin-based drugs were retrospectively analyzed. Results The clinical manifestations of imported falciparum malaria were complicated and varied and had many complications, including mainly fever, anorexia, anemia, and jaundice, etc. The symptoms were alleviated or disappeared after treatment with artemisinin, without obvious adverse drug reactions. The median time of fever reduction was 2 days, the median time of Plasmodium becoming negative was 3 days, and the median time of clinical symptom relief was 3 days. 109 cases of common falciparum malaria were treated by oral artemisinin compound or artesunate injection combined with oral artemisinin compound, including 30 cases of oral artemisinin compound treatment for 1 to 4 days (1 case relapsed) and 79 cases of artesunate injection combined with oral artemisinin compound for 4 to 6 days (4 cases relapsed). Seven severe cases were cured after long-term and high-dose treatment with artesunate injection combined with oral multiple artemisinin compounds, and the total cure rate was 95.69% (111/116). Conclusion The present study demonstrates that the treatment of falciparum malaria by oral injection of artemisinin is safe and effective, and the cure rate is high. However, some patients have recurrence of the malaria parasite after stopping artemisinin drugs. It is necessary to ensure the use of artemisinin-based drugs in a “standardized, full-process, and adequate” way to contain the risk of severe illness and drug resistance.

TiO2 nanoparticles and salinity stress in relation to artemisinin production and ADS and DBR2 expression in Artemisia absinthium L / Nanopartículas de TiO2 e estresse de salinidade em relação à produção de artemisinina e expressão de ADS e DBR2 em Artemisia absinthium L

Artemisia absinthium L. is an important herb that is widely cultivated in different parts of the world for its medicinal properties. The present study evaluated the effects of four concentrations of nanoparticles treatment (0, 10, 20 and 30 mg L-¹) and NaCl salinity stress (0, 50, 100 and 150 mM NaCl) and their interactions with respect to the expression of two key genes, i.e. DBR2 and ADS, in the biosynthesis pathway of artemisinin in A. absinthium. Total RNA was extracted and a relative gene expression analysis was carried out using Real-Time PCR. The amount of artemisinin was also determined by HPLC. All the experiments were performed as factorial in a completely randomized design in three replications. The results revealed that salinity stress and nanoparticles treatment and their interaction affected the expressions of these genes significantly. The highest levels of ADS gene expression were observed in the 30 mg L-¹ nanoparticles–treated plants in the presence of 150 mM salinity stress and the lowest levels in the 10 mg L-¹ nanoparticles–treated plants under 50 mM salinity stress. The maximum DBR2 gene expression was recorded in the 10 mg L-¹ nanoparticles–treated plants in the absence of salinity stress and the minimum expression in the 100 mM salinity-stressed plants in the absence of nanoparticles treatment. Moreover, the smallest amounts of artemisinin were observed in the 150 mM salinity-stressed plants in the absence of nanoparticles and the highest amounts in the 30 mg L-¹ nanoparticles–treated plants. The maximum amounts of artemisinin and ADS gene expression were reported from the plants in the same nanoparticles treatment and salinity stress [...].

Artemisia absinthium L. é uma erva importante que é amplamente cultivada em diferentes partes do mundo por suas propriedades medicinais. O presente estudo avaliou os efeitos de quatro concentrações de tratamento com nanopartículas (0, 10, 20 e 30 mg L-¹) e estresse de salinidade com NaCl (0, 50, 100 e 150 mM NaCl) e suas interações com relação à expressão de dois genes-chave, isto é, DBR2 e ADS, na via de biossíntese da artemisinina em A. absinthium. O RNA total foi extraído, e uma análise de expressão gênica relativa foi realizada usando PCR em tempo real. A quantidade de artemisinina também foi determinada por HPLC. Todos os experimentos foram realizados como fatorial, em delineamento inteiramente casualizado, em três repetições. Os resultados revelaram que o estresse por salinidade e o tratamento com nanopartículas e sua interação afetaram significativamente as expressões desses genes. Os níveis mais altos de expressão do gene ADS foram observados nas plantas tratadas com nanopartículas de 30 mg L-¹ na presença de estresse de salinidade de 150 mM, e os níveis mais baixos, nas plantas tratadas com nanopartículas de 10 mg L-¹ com estresse de salinidade de 50 mM. A expressão máxima do gene DBR2 foi registrada nas plantas tratadas com nanopartículas de 10 mg L-¹ na ausência de estresse de salinidade, e a expressão mínima, nas plantas estressadas com salinidade de 100 mM na ausência de tratamento com nanopartículas. Além disso, as menores quantidades de artemisinina foram observadas nas plantas com estresse de salinidade de 150 mM na ausência de nanopartículas, e as maiores quantidades, nas plantas tratadas com nanopartículas de 30 mg L-¹. As quantidades máximas de expressão de genes de artemisinina e ADS foram relatadas a partir das plantas no mesmo tratamento com nanopartículas e condições de estresse de salinidade. A esse respeito, a quantidade de artemisinina diminuiu pela metade nas [...],

TiO2 nanoparticles and salinity stress in relation to artemisinin production and ADS and DBR2 expression in Artemisia absinthium L

Abstract Artemisia absinthium L. is an important herb that is widely cultivated in different parts of the world for its medicinal properties. The present study evaluated the effects of four concentrations of nanoparticles treatment (0, 10, 20 and 30 mg L-1) and NaCl salinity stress (0, 50, 100 and 150 mM NaCl) and their interactions with respect to the expression of two key genes, i.e. DBR2 and ADS, in the biosynthesis pathway of artemisinin in A. absinthium. Total RNA was extracted and a relative gene expression analysis was carried out using Real-Time PCR. The amount of artemisinin was also determined by HPLC. All the experiments were performed as factorial in a completely randomized design in three replications. The results revealed that salinity stress and nanoparticles treatment and their interaction affected the expressions of these genes significantly. The highest levels of ADS gene expression were observed in the 30 mg L-1 nanoparticlestreated plants in the presence of 150 mM salinity stress and the lowest levels in the 10 mg L-1 nanoparticlestreated plants under 50 mM salinity stress. The maximum DBR2 gene expression was recorded in the 10 mg L-1 nanoparticlestreated plants in the absence of salinity stress and the minimum expression in the 100 mM salinity-stressed plants in the absence of nanoparticles treatment. Moreover, the smallest amounts of artemisinin were observed in the 150 mM salinity-stressed plants in the absence of nanoparticles and the highest amounts in the 30 mg L-1 nanoparticlestreated plants. The maximum amounts of artemisinin and ADS gene expression were reported from the plants in the same nanoparticles treatment and salinity stress conditions. In this regard, the amount of artemisinin was decreased by half in the plants containing the highest DBR2 gene expression. Meanwhile, no significant correlation was observed between these gene expressions and the artemisinin amount in the other nanoparticlestreated plants under different levels of salinity stress. The biosynthetic pathway of secondary metabolites appears to be very complex and dose not directly dependent on these gene expressions.

Resumo Artemisia absinthium L. é uma erva importante que é amplamente cultivada em diferentes partes do mundo por suas propriedades medicinais. O presente estudo avaliou os efeitos de quatro concentrações de tratamento com nanopartículas (0, 10, 20 e 30 mg L-1) e estresse de salinidade com NaCl (0, 50, 100 e 150 mM NaCl) e suas interações com relação à expressão de dois genes-chave, isto é, DBR2 e ADS, na via de biossíntese da artemisinina em A. absinthium. O RNA total foi extraído, e uma análise de expressão gênica relativa foi realizada usando PCR em tempo real. A quantidade de artemisinina também foi determinada por HPLC. Todos os experimentos foram realizados como fatorial, em delineamento inteiramente casualizado, em três repetições. Os resultados revelaram que o estresse por salinidade e o tratamento com nanopartículas e sua interação afetaram significativamente as expressões desses genes. Os níveis mais altos de expressão do gene ADS foram observados nas plantas tratadas com nanopartículas de 30 mg L-1 na presença de estresse de salinidade de 150 mM, e os níveis mais baixos, nas plantas tratadas com nanopartículas de 10 mg L-1 com estresse de salinidade de 50 mM. A expressão máxima do gene DBR2 foi registrada nas plantas tratadas com nanopartículas de 10 mg L-1 na ausência de estresse de salinidade, e a expressão mínima, nas plantas estressadas com salinidade de 100 mM na ausência de tratamento com nanopartículas. Além disso, as menores quantidades de artemisinina foram observadas nas plantas com estresse de salinidade de 150 mM na ausência de nanopartículas, e as maiores quantidades, nas plantas tratadas com nanopartículas de 30 mg L-1. As quantidades máximas de expressão de genes de artemisinina e ADS foram relatadas a partir das plantas no mesmo tratamento com nanopartículas e condições de estresse de salinidade. A esse respeito, a quantidade de artemisinina diminuiu pela metade nas plantas que contêm a expressão gênica DBR2 mais alta. Enquanto isso, nenhuma correlação significativa foi observada entre essas expressões gênicas e a quantidade de artemisinina nas outras plantas tratadas com nanopartículas sob diferentes níveis de estresse de salinidade. A via biossintética dos metabólitos secundários parece ser muito complexa e não depende diretamente dessas expressões gênicas.

Research progress on artemisinin antimalarial resistance of Plasmodium falciparum / 中国热带医学

@#Abstract: Malaria, an infectious disease caused by Plasmodium infection, is one of the most important public health problems worldwide. Artemisinin-based combination therapies (ACTs) are recommended by WHO as the first-line treatment for uncomplicated P. falciparum malaria in malaria-endemic areas. The application of artemisinin and its derivatives has played an integral role in reducing the global incidence of malaria. However, in recent years, the emergence and spread of artemisinin resistance has brought great challenges to global malaria control and elimination. At present, the mutation of K13 gene on chromosome 13 of Plasmodium falciparum is most closely related to artemisinin resistance, but in recent years, studies have shown that K13 cannot explain all artemisinin resistance. This article reviews the recent research progress in the field of artemisinin resistance in Plasmodium falciparum, including definition of artemisinin resistance, detection methods and molecular markers related to resistance. In addition, some of the issues discussed in this review remain controversial and require further study.