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1.
Microbiol Resour Announc ; : e0124923, 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38888324

ABSTRACT

Bacillus atrophaeus strain TL401 exhibits biocontrol activity against Botrytis cinerea on tomato and plant growth promotion. Here, we present the draft genome sequence of strain ITL401, which includes a circular chromosome with 4,213,034 bp and a guanine-cytosine content of 43.39%.

2.
J Integr Plant Biol ; 66(4): 787-809, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38477645

ABSTRACT

The recretohalophyte Limonium bicolor thrives in high-salinity environments because salt glands on the above-ground parts of the plant help to expel excess salt. Here, we characterize a nucleus-localized C3HC4 (RING-HC)-type zinc finger protein of L. bicolor named  RING  ZINC  FINGER PROTEIN  1 (LbRZF1). LbRZF1 was expressed in salt glands and in response to NaCl treatment. LbRZF1 showed no E3 ubiquitin ligase activity. The phenotypes of overexpression and knockout lines for LbRZF1 indicated that LbRZF1 positively regulated salt gland development and salt tolerance in L. bicolor. lbrzf1 mutants had fewer salt glands and secreted less salt than did the wild-type, whereas LbRZF1-overexpressing lines had opposite phenotypes, in keeping with the overall salt tolerance of these plants. A yeast two-hybrid screen revealed that LbRZF1 interacted with LbCATALASE2 (LbCAT2) and the transcription factor LbMYB113, leading to their stabilization. Silencing of LbCAT2 or LbMYB113 decreased salt gland density and salt tolerance. The heterologous expression of LbRZF1 in Arabidopsis thaliana conferred salt tolerance to this non-halophyte. We also identified the transcription factor LbMYB48 as an upstream regulator of LbRZF1 transcription. The study of LbRZF1 in the regulation network of salt gland development also provides a good foundation for transforming crops and improving their salt resistance.


Subject(s)
Arabidopsis , Plumbaginaceae , Animals , Salt Tolerance/genetics , Plumbaginaceae/genetics , Plumbaginaceae/metabolism , Salt Gland/metabolism , Zinc/metabolism , Arabidopsis/metabolism , Transcription Factors/genetics , Transcription Factors/metabolism , Zinc Fingers , Gene Expression Regulation, Plant , Plants, Genetically Modified/metabolism , Stress, Physiological/genetics , Plant Proteins/genetics , Plant Proteins/metabolism
3.
Int J Biol Macromol ; 265(Pt 1): 131007, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38508566

ABSTRACT

Derived from bountiful marine organisms (predominantly algae, fauna, and microorganisms), marine polysaccharides and marine oligosaccharides are intricate macromolecules that play a significant role in the growth and development of marine life. Recently, considerable attention has been paid to marine polysaccharides and marine oligosaccharides as auspicious natural products due to their promising biological attributes. Herein, we provide an overview of recent advances in the miscellaneous biological activities of marine polysaccharides and marine oligosaccharides that encompasses their anti-cancer, anti-inflammatory, antibacterial, antiviral, antioxidant, anti-diabetes mellitus, and anticoagulant properties. Furthermore, we furnish a concise summary of the underlying mechanisms governing the behavior of these biological macromolecules. We hope that this review inspires research on marine polysaccharides and marine oligosaccharides in medicinal applications while offering fresh perspectives on their broader facets.


Subject(s)
Biological Products , Polysaccharides , Polysaccharides/pharmacology , Oligosaccharides/pharmacology , Aquatic Organisms , Macromolecular Substances , Anti-Inflammatory Agents/pharmacology
4.
Chem Sci ; 15(9): 3060-3070, 2024 Feb 28.
Article in English | MEDLINE | ID: mdl-38425516

ABSTRACT

Boryls and their compounds are important due to their diverse range of applications in the fields of materials science and catalysis. They are an integral part of boron chemistry, which has attracted tremendous research interest over the past few decades. In this perspective, we provide an in-depth analysis of the reaction chemistry of boryl compounds from a structure and bonding perspective. We discuss the reactivity of boryls in various transition metal complexes and diborane(4) compounds towards different substrate molecules, with a focus on their nucleophilic and electrophilic properties in various reaction processes. Additionally, we briefly discuss the reactivity of boryl radicals. Our analysis sheds new light on the unique properties of boryls and their potential for catalytic applications.

5.
Plants (Basel) ; 13(3)2024 Feb 05.
Article in English | MEDLINE | ID: mdl-38337991

ABSTRACT

Flower color is one of the most important ornamental traits of tulips (Tulipa gesneriana). Five typical tulip cultivars were selected to identify the flavonoid components and analyze their key gene expression in their tepals. Firstly, after preliminary determination of the pigment type, the flavonoids were identified by UPLC-Q-TOF-MS. A total of 17 anthoxanthins were detected in the five cultivars. The total anthoxanthin content in the white tulip and the red tulip showed a similar decreasing trend, while an increasing trend was observed in the black tulip. Similarly, a total of 13 anthocyanins were detected in five tulip cultivars. The black tulip contained the largest number of anthocyanins, mainly delphinidin derivatives (Dp) and cyanidin derivatives (Cy). The total anthocyanin content (TAC) in the orange, red, and black cultivars was higher than that in the white and yellow cultivars and presented an overall increase trend along with the flower development. TgCHS, TgFLS, TgF3H, TgF3'H, TgF3'5'H, and TgDFR, as key structural genes, were involved in the flavonoid synthesis pathway, and the expression patterns of these genes are basically consistent with the components and accumulation patterns of flavonoids mentioned above. Taken together, the flower color in tulips was closely related to the composition and content of anthocyanins and anthoxanthins, which were indeed regulated by certain key structural genes in the flavonoid pathway.

6.
J Colloid Interface Sci ; 658: 639-647, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38134672

ABSTRACT

Whilst bottlebrush polymers have been studied in aqueous media for their conjectured role in biolubrication, surface forces and friction mediated by bottlebrush polymers in non-polar media have not been previously reported. Here, small-angle neutron scattering (SANS) showed that a diblock bottlebrush copolymer (oligoethyleneglycol acrylate/ethylhexyl acrylate; OEGA/EHA) formed spherical core-shell aggregates in n-dodecane (a model oil) in the polymer concentration range 0.1-2.0 wt%, with a radius of gyration Rg âˆ¼ 7 nm, comprising 40-65 polymer molecules per aggregate. The surface force apparatus (SFA) measurements revealed purely repulsive forces between surfaces bearing inhomogeneous polymer layers of thickness L âˆ¼ 13-23 nm, attributed to adsorption of a mixture of polymer chains and surface-deformed micelles. Despite the surface inhomogeneity, the polymer layers could mediate effective lubrication, demonstrating superlubricity with the friction coefficient as low as µ ∼ 0.003. The analysis of velocity-dependence of friction using the Eyring model shed light on the mechanism of the frictional process. That is, the friction mediation was consistent with the presence of nanoscopic surface aggregates, with possible contributions from a gel-like network formed by the polymer chains on the surface. These unprecedented results, correlating self-assembled polymer micelle structure with the surface forces and friction the polymer layers mediate, highlight the potential of polymers with the diblock bottlebrush architecture widespread in biological living systems, in tailoring desired surface interactions in non-polar media.

7.
Int J Mol Sci ; 24(23)2023 Nov 29.
Article in English | MEDLINE | ID: mdl-38069239

ABSTRACT

Ensuring food security for the global population is a ceaseless and critical issue. However, high-salinity and high-alkalinity levels can harm agricultural yields throughout large areas, even in largely agricultural countries, such as China. Various physical and chemical treatments have been employed in different locations to mitigate high salinity and alkalinity but their effects have been minimal. Numerous researchers have recently focused on developing effective and environmentally friendly biological treatments. Endophytes, which are naturally occurring and abundant in plants, retain many of the same characteristics of plants owing to their simultaneous evolution. Therefore, extraction of endophytes from salt-tolerant plants for managing plant growth in saline-alkali soils has become an important research topic. This extraction indicates that the soil environment can be fundamentally improved, and the signaling pathways of plants can be altered to increase their defense capacity, and can even be inherited to ensure lasting efficacy. This study discusses the direct and indirect means by which plant endophytes mitigate the effects of plant salinity stress that have been observed in recent years.


Subject(s)
Endophytes , Salinity , Alkalies , Salt Tolerance , Salt-Tolerant Plants
8.
Pulm Pharmacol Ther ; 83: 102268, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37967761

ABSTRACT

Pulmonary fibrosis (PF) is a lethal disease characterized by a progressive decline in lung function. Currently, lung transplantation remains the only available treatment for PF. However, both artemisinin (ART) and hydroxychloroquine (HCQ) possess potential antifibrotic properties. This study aimed to investigate the effects and mechanisms of a compound known as Artemisinin-Hydroxychloroquine (AH) in treating PF, specifically by targeting the TGF-ß1/Smad2/3 pathway. To do this, we utilized an animal model of PF induced by a single tracheal drip of bleomycin (BLM) in Sprague-Dawley (SD) rats. The PF animal models were administered various doses of AH, and the efficacy and safety of AH were evaluated through pulmonary function testing, blood routine tests, serum biochemistry tests, organ index measurements, and pathological examinations. Additionally, Elisa, western blotting, and qPCR techniques were employed to explore the potential molecular mechanisms of AH in treating PF. Our findings reveal that AH effectively and safely alleviate PF by inhibiting BLM-induced specific inflammation, reducing extracellular matrix (ECM) deposition, and interfering with the TGF-ß1/Smad2/3 signaling pathway. Notably, the windfall for this study is that the inhibition of ECM may initiate self-healing in the BLM-induced PF animal model. In conclusion, AH shows promise as a potential therapeutic drug for PF, as it inhibits disease progression through the TGF-ß1/Smad2/3 signaling pathway.


Subject(s)
Artemisinins , Pulmonary Fibrosis , Rats , Animals , Pulmonary Fibrosis/chemically induced , Pulmonary Fibrosis/drug therapy , Pulmonary Fibrosis/metabolism , Transforming Growth Factor beta1/metabolism , Bleomycin/toxicity , Hydroxychloroquine/adverse effects , Rats, Sprague-Dawley , Signal Transduction , Artemisinins/adverse effects , Lung
9.
J Cancer ; 14(15): 2908-2918, 2023.
Article in English | MEDLINE | ID: mdl-37781085

ABSTRACT

Objective: This study aimed to elucidate the prognostic implications of deviant expressions of long non-coding RNA (lncRNA) p53 upregulated regulator of p53 levels (PURPL), microRNA-363-3p (miR-363-3p), and ADAM metallopeptidase domain 10 (ADAM10) in patients diagnosed with ovarian serous cystadenocarcinoma (OSC). Methods: To predict and refine the targeted miRNAs and downstream target genes for PURPL, we utilized open medical databases. Through the employment of real-time RT-PCR, we conducted tissue analysis to discern the expressions of PURPL, miR-363-3p, and ADAM10 in both OSC and control tissues. The pathological correlations in the clinic and the prognostic implications of deviant expressions of PURPL, miR-363-3p, and ADAM10 in OSC patients were analyzed independently. Results: Database inquiries revealed that PURPL might target miR-363-3p, and in turn, miR-363-3p could target ADAM10. Differential expression of PURPL, miR-363-3p, and ADAM10 was observed between OSC and paired tissues. The premature version of miR-363-3p, miR-363, correlated with overall survival (OS), while ADAM10 corresponded with progression-free survival (PFS) in ovarian cancer patients. Tissue detection displayed significantly elevated expressions of PURPL and ADAM10, and conspicuously diminished expressions of miR-363-3p in OSC tissues compared to the control tissues (P<0.05). A negative correlation was observed between the expressions of PURPL and miR-363-3p, and miR-363-3p and ADAM10, while a positive correlation was found between PURPL and ADAM10 in different ovarian tissues (P<0.05). In OSC tissues, upregulation of PURPL was associated with an advanced clinical stage, TP53 mutation, and lymph node metastasis (P<0.05), downregulation of miR-363-3p was associated with a more advanced clinical stage and lymph node metastasis (P<0.05), and overexpression of ADAM10 correlated with a more advanced FIGO stage. High expressions of PURPL and ADAM10, and low expression of miR-363-3p, were linked with poor PFS and OS in OSC patients, respectively (P<0.05). In addition, OSC patients with elevated PURPL and reduced miR-363-3p, patients with elevated PURPL and ADAM10, and patients with reduced miR-363-3p and elevated ADAM10 also demonstrated worse PFS and OS, respectively (P<0.05). Conclusions: The anomalous expressions of PURPL, miR-363-3p, and ADAM10 might contribute to the pathogenesis of OSC via up-down stream regulation, and these abnormal expressions could serve as potential prognostic indicators for OSC patients.

10.
Polymers (Basel) ; 15(13)2023 Jun 28.
Article in English | MEDLINE | ID: mdl-37447493

ABSTRACT

Microbial polysaccharides are natural carbohydrates that can confer adhesion capacity to cells and protect them from harsh environments. Due to their various physiological activities, these macromolecules are widely used in food, medicine, environmental, cosmetic, and textile applications. Microbial co-culture is an important strategy that is used to increase the production of microbial polysaccharides or produce new polysaccharides (structural alterations). This is achieved by exploiting the symbiotic/antagonistic/chemo-sensitive interactions between microbes and stimulating the expression of relevant silent genes. In this article, we review the performance of polysaccharides produced using microbial co-culture in terms of yield, antioxidant activity, and antibacterial, antitumor, and anti-inflammatory properties, in addition to the advantages and application prospects of co-culture. Moreover, the potential for microbial polysaccharides to be used in various applications is discussed.

11.
Angew Chem Int Ed Engl ; 62(25): e202303470, 2023 Jun 19.
Article in English | MEDLINE | ID: mdl-37069137

ABSTRACT

The development of aryl alkyl sulfides as dichotomous electrophiles for site-selective silylation via C-S bond cleavage has been achieved. Iron-catalyzed selective cleavage of C(aryl)-S bonds can occur in the presence of ß-diketimine ligands, and the cleavage of C(alkyl)-S bonds can be achieved by t-BuONa without the use of transition metals, resulting in the corresponding silylated products in moderate to excellent yields. Mechanistic studies suggest that Fe-Si species may undergo metathesis reactions during the cleavage of C(aryl)-S bonds, while silyl radicals are involved during the cleavage of C(alkyl)-S bonds.


Subject(s)
Sulfides , Transition Elements , Catalysis , Iron , Ligands
12.
Animals (Basel) ; 13(4)2023 Feb 17.
Article in English | MEDLINE | ID: mdl-36830492

ABSTRACT

Kisspeptins are neuropeptides encoded by the kiss1 gene, and little is known about them outside the vertebrate lineage. Two kisspeptin-type neuropeptides (KPs) have been discovered in Apostichopus japonicus (AjK1 and AjK2), an edible sea cucumber, and have been linked to reproductive and metabolic regulation. In this study, we evaluated how KPs affected locomotor behavior in one control group and two treatment groups (AjK1 and AjK2). We discovered that AjK1 had a significant dose effect, primarily by shortening the stride length and duration of movement to reduce the sea cucumber movement distance, whereas AjK2 had little inhibitory effect at the same dose. The levels of phosphatidylethanolamine (PE), phosphatidylcholine (PC), uridine, glycine, and L-serine in the longitudinal muscle of A. japonicus treated with AjK1 differed significantly from those of the control, which may explain the observed changes in locomotor behavior. Treatment with AjK2 induced changes in aspartate levels. Our results imply that AjK1 is more likely than AjK2 to have a role in the regulation of A. japonicus locomotion.

13.
Angew Chem Int Ed Engl ; 62(15): e202218886, 2023 04 03.
Article in English | MEDLINE | ID: mdl-36788706

ABSTRACT

The development of environment-friendly, step economic couplings to generate structurally diverse macrocyclic compounds is highly desirable but poses a marked challenge. Inspired by the C-H oxidation mechanism of cytochromes P450, an unprecedented and practical RhIII -catalyzed acylmethylation macrocyclization via C-H/O2 dual activation has been developed by us. The process of macrocyclization is facilitated by a synergic coordination from pyridine and ester group. Interestingly, the reaction mode derives from a three-component coupling which differs from established olefination and alkylation paths. Density functional theory (DFT) calculations and control experiments revealed the mechanism of this unique C-H/O2 dual activation. The newly achieved acylmethylation macrocyclic products and their derivatives showed a potent anti-H1N1 bioactivity, which may provide an opportunity for the discovery of novel anti-H1N1 macrocyclic leading compounds.


Subject(s)
Influenza, Human , Rhodium , Humans , Catalysis , Oxidation-Reduction , Alkylation
14.
Chem Asian J ; 18(4): e202201218, 2023 Feb 14.
Article in English | MEDLINE | ID: mdl-36639231

ABSTRACT

Heavier main-group element-catalyzed reactions provide an increasingly attractive tool to perform transformations mimicking the behaviors of transition metal catalysts. Recently, Magre and Cornella reported a Bi-catalyzed synthesis of aryl sulfonyl fluorides, which involves a fundamental organometallic step of SO2 insertion into the Bi-Ph bond. Our theoretical studies reveal that i) the ability of hypervalent coordination of the Bi(III) center allows facile coordination sphere expansion for the SO2 coordination via one oxygen atom; and ii) the high polarity of the Bi-Ph bond makes the Ph migration from the Bi(III) center feasible. These features enable the heavier main group element to resemble the transition metal having flexibility for ligand association and dissociation. Furthermore, iii) the available π electron pair of the migrating Ph group stabilizes the SO2 insertion transition state by maintaining interaction with the Bi(III) center during migration. The insight helps us better understand the heavier main-group catalysis.

15.
Angew Chem Int Ed Engl ; 62(5): e202216373, 2023 Jan 26.
Article in English | MEDLINE | ID: mdl-36465061

ABSTRACT

The transition metal-catalyzed cross-coupling reaction with Fischer metal carbene intermediates bearing an electron-rich alkoxyl or siloxyl group remains a big challenge due to the lack of readily available corresponding carbene precursors. Herein, we report the coupling of alkynes with the Fischer-type copper carbene species bearing a α-siloxyl group, which could be in situ generated from acylsilanes catalytically under photoirradiation and redox-neutral conditions. The side-arm modified bisoxazoline (SaBox) ligands prove to be crucial for this coupling reaction, which provides the corresponding alkynyl alcohol in high yields with remarkable heterocycle tolerance and broad substrate scope.

16.
Chem Sci ; 13(47): 14165-14178, 2022 Dec 07.
Article in English | MEDLINE | ID: mdl-36540825

ABSTRACT

The choice of backbone linker for two ortho-bis-(9-borafluorene)s has a great influence on the LUMO located at the boron centers and, therefore, the reactivity of the respective compounds. Herein, we report the room temperature rearrangement of 1,2-bis-(9-borafluorenyl)-ortho-carborane, C2B10H10-1,2-[B(C12H8)]2 ([2a]) featuring o-carborane as the inorganic three-dimensional backbone and the synthesis of 1,2-bis-(9-borafluorenyl)benzene, C6H4-1,2-[B(C12H8)]2 (2b), its phenylene analog. DFT calculations on the transition state for the rearrangement support an intramolecular C-H bond activation process via an SEAr-like mechanism in [2a], and predicted that the same rearrangement would take place in 2b, but at elevated temperatures, which indeed proved to be the case. The rearrangement gives access to 3a and 3b as dibora-benzo[a]fluoroanthene isomers, a form of diboron polycyclic aromatic hydrocarbon (PAH) that had yet to be explored. The isolated compounds 2b, 3a, and 3b were fully characterized by NMR, HRMS, cyclic voltammetry (CV), single-crystal X-ray diffraction analysis, and photophysical measurements, supported by DFT and TD-DFT calculations.

17.
Int J Mol Sci ; 23(22)2022 Nov 11.
Article in English | MEDLINE | ID: mdl-36430364

ABSTRACT

Soil salinization is one of the major factors restricting crop growth and agricultural production worldwide. Recretohalophytes have developed unique epidermal structures in their aboveground tissues, such as salt glands or salt bladders, to secrete excess salt out of the plant body as a protective mechanism from ion damage. Three hypotheses were proposed to explain how salt glands secrete salts: the osmotic hypothesis, a hypothesis similar to animal fluid transport, and vesicle-mediated exocytosis. However, there is no direct evidence to show whether the salt gland-secreted liquid contains landmark proteins or peptides which would elucidate the salt secretion mechanism. In this study, we collected the secreted liquid of salt glands from Limonium bicolor, followed by extraction and identification of its constituent proteins and peptides by SDS-PAGE and mass spectrometry. We detected 214 proteins and 440 polypeptides in the salt gland-secreted droplets of plants grown under control conditions. Unexpectedly, the proportion of energy metabolism-related proteins increased significantly though only 16 proteins and 35 polypeptides in the droplets of salt-treated plants were detected. In addition, vesicle transport proteins such as the Golgi marker enzyme glycosyltransferase were present in the secreted sap of salt glands from both control and salt-treated plants. These results suggest that trans-Golgi network-mediated vesicular transport and energy production contributes to salt secretion in salt glands.


Subject(s)
Proteomics , Salt Gland , Animals , Salt Gland/metabolism , Plant Leaves/metabolism , Sodium Chloride/metabolism , Sodium Chloride, Dietary/metabolism , Energy Metabolism
18.
Plant Dis ; 2022 Oct 28.
Article in English | MEDLINE | ID: mdl-36306442

ABSTRACT

Atractylodes lancea Thunb. DC (cangzhu) is a traditional Chinese medicinal plant (Cai et al., 2020). In June 2020, leaf spots were observed in A. lancea plants at the Chongqing Institute of Medicinal Plant Cultivation located in Nanchuan District, Chongqing, China (29°8'26.46″ N, 107°13'23'21″ E). Approximately 75% of the plants displayed leaf spot, partial leaf wilting, and stunted growth, and some plants died. To determine the cause of this disease, five typical leaf spots were cut into small pieces. The pieces were successively surface-disinfected with 0.5% NaClO for 1 min and 75% ethanol for 30 s, washed thrice with sterile water, and placed on potato dextrose agar (PDA) to incubate at 25 ℃. These isolates initially formed abundant white aerial mycelium, then gradually developed a rose pigmentation with a brownish color in the center and grayish rose at the periphery of the colony (Li et al. 2019). Mycelial tips were picked and placed on carnation leaf agar (CLA) and inoculated for 7 days. The macroconidia of the isolates were slender, distinctively curved in the bottom half of the apical cell, and sickle-shaped, with 3-4 septa. They ranged in size from 16.68-26.49 × 1.48-2.34 µm (n=50). The microconidia were fusiform with or without one septum. Their size ranged from 6.19-11.02 × 1.25-1.43 µm (n=50) (Li et al. 2019). The morphological characteristics of the isolates were consistent with those of Fusarium spp. PCR amplification and DNA sequencing of the internal transcribed spacer (ITS) region and ß-tubulin (TUB2) gene were performed using the primers ITS1/ITS4 (White et al. 1990) and Bt-2a/Bt-2b (Robideau et al. 2011), respectively. BLASTn analysis revealed that the ITS sequences of the isolates were 100% identical to those of the F. acuminatum isolates from the Fusarium MLST database (http://isolate.fusariumdb.org/guide.php). Further analysis revealed that the TUB2 sequences were 99.14% identical to those of the F. acuminatum strain S16 isolates (MF662644) from the GeneBank database of the NCBI server. Based on the morphology and sequence analyses, the isolates were identified as F. acuminatum. Pathogenicity tests were conducted on 1.5-year-old A. lancea plants by inoculating spore suspensions under greenhouse conditions (25°C). For this, wound were made on leaves by piercing with sterilized toothpicks. 30 µl of spore suspension containing 2 × 106 conidia/ml was placed on each wound. Wounds on the leaves of control plants were inoculated with 10 µl of sterile distilled water. There were three plants for each treatment. After incubation at 25 °C for 5 days in a greenhouse, the leaves of the treated plants all showed partial wilting, consistent with the field observations. No symptoms were observed in controlled plants. The fungi were again isolated from the symptomatic tissues and were identical to the original isolate. The experiment was repeated twice with similar results. Pathogenicity symptoms were similar to what was first observed in the field and the isolated fungi were verified based on morphological characteristics, thus fulfilling Koch's postulate. To the best of our knowledge, this is the first time that A. lancea leaf spot caused by F. acuminatum has been discovered in China. The leaf spot caused by F. acuminatum on A. lancea has serious yield loss, and proper control measures should be applied.

20.
Mol Omics ; 18(8): 716-730, 2022 09 26.
Article in English | MEDLINE | ID: mdl-35960011

ABSTRACT

BACKGROUND: cerebral malaria (CM) is an important complication of malaria with a high mortality rate. Artesunate is recommended as the first-line artemisinin compound treatment for severe malaria. Due to the difficulty of obtaining brain tissue samples clinically, the use of animals to research host responses to CM parasite infections is necessary. Rodent malaria models allow for detailed time series studies of host responses in multiple organs. To date, studies on the transcriptome of severe malaria are only limited to the parasites in the peripheral blood of patients, and there is little data on the transcriptional changes in brain tissue in mice with CM treated with artesunate. METHOD AND RESULT: in this study, fresh tissue samples (three biological replicates per mouse) from the same area of the brain in each animal were collected from the uninfected, Plasmodium berghei ANKA-infected and artesunate-treated C57BL/6 mice, and then transcriptome research was performed by the RNA-seq technique. Differentially expressed genes (DEGs) included Il-21, Tnf, Il-6, Il-1ß, Il-10, Ifng, and Icam-1. Among which, Il-6, Il-10, Tnf-α and Il-1ß were further verified and validated via qRT-PCR and ELISA. This revealed that Il-1ß (p < 0.0001), Il-10 (p < 0.05) and Tnf-α (p < 0.05) were significantly up-regulated in the Pb ANKA-infected versus uninfected group, while Il-1ß (p < 0.0001) and Tnf-α (p < 0.05) were significantly down-regulated after artesunate treatment. All DEGs were closely related to the top 3 artesunate treatment pathways, including the JAK-STAT signaling pathway, apoptosis, and Toll-like receptor signaling pathway. CONCLUSION: the mechanism of improving the prognosis of cerebral malaria by artesunate may not only involve the killing of plasmodium but also the inhibition of a cytokine storm in the host. This study provides new insights into the molecular mechanism by which artesunate improves the prognosis of cerebral malaria.


Subject(s)
Antimalarials , Artemisinins , Malaria, Cerebral , Animals , Anti-Inflammatory Agents/therapeutic use , Antimalarials/pharmacology , Antimalarials/therapeutic use , Artemisinins/pharmacology , Artemisinins/therapeutic use , Artesunate/pharmacology , Artesunate/therapeutic use , Disease Models, Animal , Gene Expression Profiling , Intercellular Adhesion Molecule-1/therapeutic use , Interleukin-10/therapeutic use , Interleukin-6/therapeutic use , Lead/therapeutic use , Malaria, Cerebral/drug therapy , Malaria, Cerebral/genetics , Malaria, Cerebral/metabolism , Mice , Mice, Inbred C57BL , RNA-Seq , Toll-Like Receptors/therapeutic use , Tumor Necrosis Factor-alpha/therapeutic use
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