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1.
Infection ; 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38717734

RESUMO

PURPOSE: The principal objective of this project was to review and thoroughly examine the chemical characteristics, pharmacological activity, and quantification methods associated with contezolid. METHODS: The article was based on published and ongoing preclinical and clinical studies on the application of contezolid. These studies included experiments on the physicochemical properties of contezolid, in vitro antimicrobial research, in vivo antimicrobial research, and clinical trials in various phases. There were no date restrictions on these studies. RESULTS: In June 2021, contezolid was approved for treating complicated skin and soft tissue infections. The structural modification of contezolid has resulted in better efficacy compared to linezolid. It inhibits bacterial growth by preventing the production of the functional 70S initiation complex required to translate bacterial proteins. The current evidence has indicated a substantial decline in myelosuppression and monoamine oxidase inhibition without impairing its antibacterial properties. Contezolid was found to have a more significant safety profile and to be metabolised by flavin monooxygenase 5, reducing the risk of harmful effects due to drug-drug interactions. Adjusting doses is unnecessary for patients with mild to moderate renal or hepatic insufficiency. CONCLUSION: As an oral oxazolidinone antimicrobial agent, contezolid is effective against multi-drug resistant Gram-positive bacteria. The introduction of contezolid provided a new clinical option.

2.
Curr Neurovasc Res ; 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38629369

RESUMO

BACKGROUND: Ferroptosis is an iron-dependent regulating programmed cell death discovered recently that has been receiving much attention in traumatic brain injury (TBI). xCT, a major functional subunit of Cystine/glutamic acid reverse transporter (System Xc-), promotes cystine intake and glutathione biosynthesis, thereby protecting against oxidative stress and ferroptosis. OBJECTIVE: The intention of this research was to verify the hypothesis that electroacupuncture (EA) exerted an anti-ferroptosis effect via an increase in the expression of xCT and activation of the System Xc-/GSH/GPX4 axis in cortical neurons of TBI rats. METHODS: After the TBI rat model was prepared, animals received EA treatment at GV20, GV26, ST36 and PC6, for 15min. The xCT inhibitor Sulfasalazine (SSZ) was administered 2h prior to model being prepared. The degree of neurological impairment was evaluated by means of TUNEL staining and the modified neurological severity score (mNSS). Specific indicators of ferroptosis (Ultrastructure of mitochondria, Iron and ROS) were detected by transmission electron microscopy (TEM), Prussian blue staining (Perls stain) and flow cytometry (FCM), respectively. GSH synthesis and metabolism-related factors in the content of the cerebral cortex were detected by an assay kit. Real-time quantitative PCR (RT-QPCR), Western blot (WB), and immunofluorescence (IF) were used for detecting the expression of System Xc-/GSH/GPX4 axisrelated proteins in injured cerebral cortex tissues. RESULTS: EA successfully relieved nerve damage within 7 days after TBI, significantly inhibited neuronal ferroptosis, upregulated the expression of xCT and System Xc-/GSH/GPX4 axis forward protein and promoted glutathione (GSH) synthesis and metabolism in the injured area of the cerebral cortex. However, aggravation of nerve damage and increased ferroptosis effect were found in TBI rats injected with xCT inhibitors. CONCLUSIONS: EA inhibits neuronal ferroptosis by up-regulated xCT expression and by activating System Xc-/GSH/GPX4 axis after TBI, confirming the relevant theories regarding the EA effect in treating TBI and providing theoretical support for clinical practice.

3.
Plants (Basel) ; 13(6)2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38592766

RESUMO

α-Linolenic acid (ALA) is an important nutrient component in rapeseed oil, and rapeseed breeders want to either restrain or enhance the function of fatty acid desaturases (FADs) in the ALA biosynthesis pathway. To determine the reason for the upregulation of rapeseed BnFAD genes in two high-ALA accessions, R8Q10 and YH25005, we compared their transcriptome profiles in the seed at 24 days after pollination (DAP) with those of two low-ALA lines, A28 and SW. The expression levels of twenty-eight important genes in the seed samples at 20, 27, and 34 DAP were also investigated using an RT-qPCR. The expression levels of genes involved in flavonoid and proanthocyanidin synthesis, including BnCHS, BnCHI, BnDFR, BnFLS1, BnLDOX, BnBAN, BnTT10, and BnTT12 and genes encoding the transcription factors BnTT1, BnTT2, BnTT8, and BnTT16 were lower in R8Q10 and YH25005 than in A28 and SW. The expression levels of genes encoding master transcription factors in embryo development, such as BnLEC1, BnABI3, BnFUS3, BnL1L, BnAREB3, and BnbZIP67, were elevated significantly in the two high-ALA accessions. Combined with previous results in the Arabidopsis and rapeseed literature, we speculated that the yellow-seededness genes could elevate the activity of BnLEC1, BnABI3, BnFUS3, and BnbZIP67, etc., by reducing the expression levels of several transparent testa homologs, resulting in BnFAD3 and BnFAD7 upregulation and the acceleration of ALA synthesis. Yellow-seededness is a favorable factor to promote ALA synthesis in the two high-ALA accessions with the yellow-seeded trait. These findings provide initial insights into the transcriptomic differences between high-/low-ALA germplasms and a theoretic basis for seed quality breeding.

4.
J Med Virol ; 96(4): e29595, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38587217

RESUMO

Systemic autoimmune diseases (SADs) are a growing spectrum of autoimmune disorders that commonly affect multiple organs. The role of Epstein-Barr virus (EBV) infection or reactivation as a trigger for the initiation and progression of SADs has been established, while the relationship between EBV envelope glycoproteins and SADs remains unclear. Here, we assessed the levels of IgG, IgA, and IgM against EBV glycoproteins (including gp350, gp42, gHgL, and gB) in serum samples obtained from patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), and found that RA and SLE patients exhibited a statistically significant increase in the levels of 8 and 11 glycoprotein antibodies, respectively, compared to healthy controls (p < 0.05). The LASSO model identified four factors as significant diagnostic markers for RA: gp350 IgG, gp350 IgA, gHgL IgM, and gp42 IgA; whereas for SLE it included gp350 IgG, gp350 IgA, gHgL IgA, and gp42 IgM. Combining these selected biomarkers yielded an area under the curve (AUC) of 0.749 for RA and 0.843 for SLE. We subsequently quantified the levels of autoantibodies associated with SADs in mouse sera following immunization with gp350. Remarkably, none of the tested autoantibody levels exhibited statistically significant alterations. Elevation of glycoprotein antibody concentration suggests that Epstein-Barr virus reactivation and replication occurred in SADs patients, potentially serving as a promising biomarker for diagnosing SADs. Moreover, the absence of cross-reactivity between gp350 antibodies and SADs-associated autoantigens indicates the safety profile of a vaccine based on gp350 antigen.


Assuntos
Artrite Reumatoide , Doenças Autoimunes , Infecções por Vírus Epstein-Barr , Lúpus Eritematoso Sistêmico , Humanos , Animais , Camundongos , Infecções por Vírus Epstein-Barr/complicações , Herpesvirus Humano 4 , Anticorpos Antivirais , Artrite Reumatoide/complicações , Glicoproteínas , Doenças Autoimunes/complicações , Imunoglobulina G , Imunoglobulina A , Imunoglobulina M
5.
Nat Plants ; 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38600265

RESUMO

NARROW LEAF1 (NAL1) exerts a multifaceted influence on leaf morphology and crop yield. Recent crystal study proposed that histidine 233 (H233) is part of the catalytic triad. Here we report that unlike suggested previously, H234 instead of H233 is a component of the catalytic triad alongside residues D291 and S385 in NAL1. Remarkably, residue 233 unexpectedly plays a pivotal role in regulating NAL1's proteolytic activity. These findings establish a strong foundation for utilizing NAL1 in breeding programs aimed at improving crop yield.

6.
Nucleic Acids Res ; 52(6): 3406-3418, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38412313

RESUMO

RNA helicases function as versatile enzymes primarily responsible for remodeling RNA secondary structures and organizing ribonucleoprotein complexes. In our study, we conducted a systematic analysis of the helicase-related activities of Escherichia coli HrpA and presented the structures of both its apo form and its complex bound with both conventional and non-canonical DNAs. Our findings reveal that HrpA exhibits NTP hydrolysis activity and binds to ssDNA and ssRNA in distinct sequence-dependent manners. While the helicase core plays an essential role in unwinding RNA/RNA and RNA/DNA duplexes, the N-terminal extension in HrpA, consisting of three helices referred to as the APHB domain, is crucial for ssDNA binding and RNA/DNA duplex unwinding. Importantly, the APHB domain is implicated in binding to non-canonical DNA structures such as G-quadruplex and i-motif, and this report presents the first solved i-motif-helicase complex. This research not only provides comprehensive insights into the multifaceted roles of HrpA as an RNA helicase but also establishes a foundation for further investigations into the recognition and functional implications of i-motif DNA structures in various biological processes.


Assuntos
DNA Helicases , Proteínas de Escherichia coli , Sequência de Aminoácidos , DNA/química , DNA Helicases/metabolismo , DNA de Cadeia Simples/genética , Escherichia coli/metabolismo , RNA/química , RNA Helicases/genética , Proteínas de Escherichia coli/metabolismo
7.
J Nat Prod ; 87(2): 228-237, 2024 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-38266493

RESUMO

As a model liverwort, Marchantia polymorpha contains various flavone glucuronides with cardiovascular-promoting effects and anti-inflammatory properties. However, the related glucuronosyltransferases have not yet been reported. In this study, two bifunctional UDP-glucuronic acid/UDP-glucose:flavonoid glucuronosyltransferases/glucosyltransferases, MpUGT742A1 and MpUGT736B1, were identified from M. polymorpha. Extensive enzymatic assays found that MpUGT742A1 and MpUGT736B1 exhibited efficient glucuronidation activity for flavones, flavonols, and flavanones and showed promiscuous regioselectivity at positions 3, 6, 7, 3', and 4'. These enzymes catalyzed the production of a variety of flavonoid glucuronides with medicinal value, including apigenin-7-O-glucuronide and scutellarein-7-O-glucuronide. With the use of MpUGT736B1, apigenin-4'-O-glucuronide and apigenin-7,4'-di-O-glucuronide were prepared by scaled-up enzymatic catalysis and structurally identified by NMR spectroscopy. MpUGT742A1 also displayed glucosyltransferase activity on the 7-OH position of the flavanones using UDP-glucose as the sugar donor. Furthermore, we constructed four recombinant strains by combining the pathway for increasing the UDP-glucuronic acid supply with the two novel UGTs MpUGT742A1 and MpUGT736B1. When apigenin was used as a substrate, the extracellular apigenin-4'-O-glucuronide and apigenin-7,4'-di-O-glucuronide production obtained from the Escherichia coli strain BB2 reached 598 and 81 mg/L, respectively. Our study provides new candidate genes and strategies for the biosynthesis of flavonoid glucuronides.


Assuntos
Flavanonas , Marchantia , Flavonoides/química , Apigenina , Glucuronídeos/metabolismo , Marchantia/metabolismo , Glucuronosiltransferase/química , Glucuronosiltransferase/metabolismo , Escherichia coli/metabolismo , Glucose , Ácido Glucurônico , Difosfato de Uridina
8.
PLoS One ; 19(1): e0296079, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38190396

RESUMO

Phenylpropanoids play important roles in plant physiology and the enzyme 4-coumarate: coenzyme A ligase (4CL) catalyzes the formation of thioesters. Despite extensive characterization in various plants, the functions of 4CLs in the liverwort Marchantia paleacea remain unknown. Here, four 4CLs from M. paleacea were isolated and functionally analyzed. Heterologous expression in Escherichia coli indicated the presence of different enzymatic activities in the four enzymes. Mp4CL1 and Mp4CL2 were able to convert caffeic, p-coumaric, cinnamic, ferulic, dihydro-p-coumaric, and 5-hydroxyferulic acids to their corresponding CoA esters, while Mp4CL3 and Mp4CL4 catalyzed none. Mp4CL1 transcription was induced when M. paleacea thalli were treated with methyl jasmonate (MeJA). The overexpression of Mp4CL1 increased the levels of lignin in transgenic Arabidopsis. In addition, we reconstructed the flavanone biosynthetic pathway in E. coli. The pathway comprised Mp4CL1, co-expressed with chalcone synthase (CHS) from different plant species, and the efficiency of biosynthesis was optimal when both the 4CL and CHS were obtained from the same species M. paleacea.


Assuntos
Arabidopsis , Flavanonas , Marchantia , Ligases , Marchantia/genética , Lignina , Escherichia coli/genética , Clonagem Molecular
9.
Opt Lett ; 49(2): 367-370, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38194570

RESUMO

We investigate optical transmission in cavity magnon polaritons and discover a complex multi-window magnetically induced transparency and a bistability with magnetic and optical characteristics. With the regulation of Kerr nonlinear effects and driven fields, a complex multi-window resonant transmission with fast and slow light effects appears, which includes transparency and absorption windows. The magnetically induced transparency and absorption can be explained by the destructive and constructive interference between different excitation pathways. Moreover, we demonstrate the bistability of magnons and photons with a hysteresis loop, where magnetic and optical bistabilities can induce and control each other. Our results pave a new way, to the best of our knowledge, for implementing a room-temperature multiband quantum memory.

10.
J Mol Biol ; 436(2): 168373, 2024 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-37992890

RESUMO

The G-quadruplex (G4) is a distinct geometric and electrophysical structure compared to classical double-stranded DNA, and its stability can impede essential cellular processes such as replication, transcription, and translation. This study focuses on the BsPif1 helicase, revealing its ability to bind independently to both single-stranded DNA (ssDNA) and G4 structures. The unfolding activity of BsPif1 on G4 relies on the presence of a single tail chain, and the covalent continuity between the single tail chain and the G4's main chain is necessary for efficient G4 unwinding. This suggests that ATP hydrolysis-driven ssDNA translocation exerts a pull force on G4 unwinding. Molecular dynamics simulations identified a specific region within BsPif1 that contains five crucial amino acid sites responsible for G4 binding and unwinding. A "molecular wire stripper" model is proposed to explain BsPif1's mechanism of G4 unwinding. These findings provide a new theoretical foundation for further exploration of the G4 development mechanism in Pif1 family helicases.


Assuntos
Trifosfato de Adenosina , DNA Helicases , DNA de Cadeia Simples , Quadruplex G , Trifosfato de Adenosina/química , DNA de Cadeia Simples/química , Hidrólise , Simulação de Dinâmica Molecular , DNA Helicases/química
11.
Phys Rev E ; 108(3-1): 034214, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37849096

RESUMO

The nonlinear Landau-Zener-Stückelberg-Majorana (LZSM) tunneling dynamics and interferometry of an extended Bose-Hubbard flux ladder are studied. Based on the mean-field theory, the dispersion relation of the system is given, and it is found that loop structures periodically appear in the band structure and the nonlinear LZSM interference occurs naturally without Floquet engineering, which can be effectively modulated by atomic interactions. The nonlinear energy bands and the unique chirality feature of the flux ladder system can be identified through the dynamics of nonlinear Landau-Zener tunneling. Remarkably, the critical position of the noise in the interference pattern can be employed to identify the loop structure in the energy band, establishing an effective link between the nonlinear loop structure and LZSM interferometry. The position, intensity, symmetry, and width of interference patterns strongly depend on the magnetic field, atomic interactions, rung-to-leg coupling ratio, and energy bias, which provides an effective way to measure these parameters using the nonlinear LZSM interferometry. This paper further expands the dynamics of flux ladder systems to complex interaction regions and has potential applications in the precise measurement of related nonlinear systems.

12.
Huan Jing Ke Xue ; 44(10): 5800-5812, 2023 Oct 08.
Artigo em Chinês | MEDLINE | ID: mdl-37827795

RESUMO

To explore the effects of long-term tillage on bacterial community structure in different soil layers of dryland wheat fields and its relationship with soil physicochemical properties, a long-term field experiment was conducted from 2016 to 2021 in Wenxi Experimental Demonstration Base of Shanxi Agricultural University, Shanxi Province. We studied the effects of no-tillage (NT), subsoiling-tillage (ST), and deep plowing (DP) on soil physicochemical properties; α and ß diversity of the bacterial community; and dominant and different species of phyla and genera in different soil layers. Additionally, PICRUSt2 was used to predict the metabolic function of soil bacterial community. The results revealed that subsoiling-tillage and deep plowing significantly increased the soil water content in the 20-40 cm soil layer and significantly decreased the soil organic carbon content in the 0-20 cm soil layer compared with that under no-tillage for five consecutive years. Compared with that under deep plowing, subsoiling-tillage significantly increased soil water content, soil organic carbon content, dissolved organic carbon content, and dissolved organic nitrogen content in the 0-20 cm soil layer. Compared with that under no-tillage, subsoiling-tillage and deep plowing increased the α diversity of the soil bacterial community in the 0-40 cm soil layer, and subsoiling-tillage was higher than deep plowing. Compared with that under no-tillage, subsoiling-tillage and deep plowing significantly increased the relative abundances of Acidobacteria and Nitrospirae in the 0-20 cm soil layer and Acidobacteria, Chloroflexi, Gemmatimonadetes, Rokubacteria, GAL15, and Nitrospirae in the 20-40 cm soil layer. Compared with that under no-tillage, subsoiling-tillage and deep plowing significantly increased the relative abundance of Nitrospira in the 0-20 cm soil layer and Rubrobacter and Streptomyces in the 20-40 cm soil layer. Compared with that under deep plowing, subsoiling-tillage significantly increased the relative abundance of Acidobacteria and Gemmatimonadetes in the 0-40 cm soil layer. Redundancy analysis demonstrated that the contents of soil organic carbon, dissolved organic carbon, and dissolved organic nitrogen in the 0-20 cm soil layer exerted positive effects on Actinobacteria and Blastococcus, and the soil water content in the 0-40 cm soil layer exerted positive effects on Acidobacteria, Chloroflexi, and Gemmatimonadetes under subsoiling-tillage. The results of PICRUSt2 prediction showed that subsoiling-tillage and deep plowing significantly increased the relative abundance of amino acid metabolism and the metabolism of cofactors and vitamins but decreased the relative abundance of lipid metabolism of bacterial communities in the 20-40 cm soil layer compared with that under no-tillage. Compared with that under deep plowing, subsoiling-tillage significantly increased the relative abundances of amino acid metabolism in the 0-40 cm soil layer and other amino acid metabolism in the 0-20 cm soil layer. In conclusion, subsoiling-tillage or deep plowing could increase the soil water content, α diversity of the soil bacterial community, and their metabolic capacity in the dryland wheat fields during the summer fallow period. The relative abundance of Acidobacteria and Gemmatimonadetes and the ability of amino acid metabolism of the bacterial community were increased by subsoiling-tillage, and thus the contents of soil dissolved organic carbon and dissolved nitrogen can be increased.


Assuntos
Solo , Triticum , Humanos , Solo/química , Matéria Orgânica Dissolvida , Carbono/análise , Agricultura/métodos , Água/análise , China , Acidobacteria , Aminoácidos
13.
Biomed Environ Sci ; 36(8): 779-782, 2023 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-37711091

RESUMO

In August 2021, three students with diarrhea from the same school visited a local hospital in the S district of Beijing. An epidemic investigation showed that there were more students with diarrhea in the same school and they had one meal together. Campylobacter jejuni was isolated from both patients with diarrhea and asymptomatic food handlers; however, the latter also carried Campylobacter coli. Phylogenomic analysis showed that there was a campylobacteriosis outbreak among the students, and the asymptomatic food handler may have been the source of the infection. Routine inspection and surveillance for Campylobacter is needed for the food producing staff, particularly those cooking in the cafeteria in schools or other public food services.


Assuntos
Infecções por Campylobacter , Campylobacter , Gastroenterite , Humanos , Infecções por Campylobacter/epidemiologia , Diarreia , Surtos de Doenças
14.
J Agric Food Chem ; 71(34): 12775-12784, 2023 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-37604680

RESUMO

Isoflavones are rich natural compounds present in legumes and are essential for plant growth and development. Moreover, they are beneficial for animals and humans. Isoflavones are primarily found as glycoconjugates, including calycosin-7-O-ß-d-glucoside (CG) in Astragalus membranaceus, a legume. However, the glycosylation mechanism of isoflavones in A. membranaceus remains unclear. In the present study, three uridine diphosphate (UDP)-glycosyltransferases (UGTs) that may be involved in the biosynthesis of isoflavone were identified in the transcriptome of A. membranaceus. Enzymatic analysis revealed that AmUGT88E29 and AmUGT88E30 had high catalytic activity toward isoflavones in vitro. In addition, AmUGT88E29 and AmUGT88E30 could accept various flavones, flavanones, flavonols, dihydroflavonols, and dihydrochalcones as substrates. AmUGT71G10 was only active against phloretin and dihydroresveratrol. Overexpression of AmUGT88E29 significantly increased the contents of CG, an isoflavone glucoside, in the hairy roots of A. membranaceus. This study provided candidate AmUGT genes for the potential metabolic engineering of flavonoid compounds in plants and a valuable resource for studying the calycosin glycosides biosynthesis pathway.


Assuntos
Fabaceae , Isoflavonas , Animais , Humanos , Glicosiltransferases/genética , Astragalus propinquus/genética , Glicosilação , Flavonoides , Verduras , Glucosídeos
15.
J Cell Physiol ; 238(10): 2499-2511, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37642286

RESUMO

Family 1 UDP-glycosyltransferases (UGTs) are known to glycosylate multiple secondary plant metabolites and have been extensively studied. The increased availability of plant genome resources allows the identification of wide gene families, both functional and organizational. In this investigation, two MpUGT isoforms were cloned and functionally characterized from liverworts marchantia polymorpha and had high glycosylation activity against several flavonoids. MpUGT735A2 protein, in particular, tolerates a wide spectrum of substrates (flavonols, flavanones, flavones, stilbenes, bibenzyls, dihydrochalcone, phenylpropanoids, xanthones, and isoflavones). Overexpression of MpUGT735A2 and MpUGT743A1 in Arabidopsis thaliana enhances the accumulation of 3-O-glycosylated flavonol (kaempferol 3-O-glucoside-7-O-rhamnose), consistent with its in vitro enzymatic activity. Docking and mutagenesis techniques were applied to identify the structural and functional properties of MpUGT735A2 with promiscuous substrates. Mutation of Pro87 to Ser, or Gln88 to Val, substantially altered the regioselectivity for luteolin glycosylation, predominantly from the 3'-O- to the 7-O-position. The results were elucidated by focusing on the novel biocatalysts designed for producing therapeutic flavonoids. This investigation provides an approach to modulate MpUGT735A2 as a candidate gene for diverse glycosylation catalysis and a tool to design GTs with new substrate specificities for biomedical applications.

16.
Elife ; 122023 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-37458359

RESUMO

Decidualization is a process in which endometrial stromal fibroblasts differentiate into specialized secretory decidual cells and essential for the successful establishment of pregnancy. The underlying mechanism during decidualization still remains poorly defined. Because decidualization and fibroblast activation share similar characteristics, this study was to examine whether fibroblast activation is involved in decidualization. In our study, fibroblast activation-related markers are obviously detected in pregnant decidua and under in vitro decidualization. ACTIVIN A secreted under fibroblast activation promotes in vitro decidualization. We showed that arachidonic acid released from uterine luminal epithelium can induce fibroblast activation and decidualization through PGI2 and its nuclear receptor PPARδ. Based on the significant difference of fibroblast activation-related markers between pregnant and pseudopregnant mice, we found that embryo-derived TNF promotes CPLA2α phosphorylation and arachidonic acid release from luminal epithelium. Fibroblast activation is also detected under human in vitro decidualization. Similar arachidonic acid-PGI2-PPARδ-ACTIVIN A pathway is conserved in human endometrium. Collectively, our data indicate that embryo-derived TNF promotes CPLA2α phosphorylation and arachidonic acid release from luminal epithelium to induce fibroblast activation and decidualization.


Assuntos
Decídua , PPAR delta , Gravidez , Feminino , Humanos , Animais , Camundongos , Decídua/metabolismo , PPAR delta/metabolismo , Ácido Araquidônico , Endométrio , Fibroblastos , Células Estromais/metabolismo
17.
World J Clin Cases ; 11(17): 4072-4078, 2023 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-37388798

RESUMO

BACKGROUND: Angioimmunoblastic T-cell lymphoma (AITL), a unique subtype of peripheral T-cell lymphoma, has relatively poor outcomes. High-dose chemotherapy with autologous stem cell transplantation (ASCT) can achieve complete remission and improve outcomes. Unfortunately, subsequent T-cell lymphoma-triggered hemophagocytic lymphohistiocytosis (HLH) has a worse prognosis than B-cell lymphoma-triggered HLH. CASE SUMMARY: We here report a 50-year-old woman with AITL who achieved a favorable outcome after developing HLH 2 mo after receiving high-dose chemotherapy/ ASCT. The patient was initially admitted to our hospital because of multiple enlarged lymph nodes. The final pathologic diagnosis, made on biopsy of a left axillary lymph node was AITL (Stage IV, Group A). Four cycles of the following chemotherapy regimen were administered: Cyclophosphamide 1.3 g, doxorubicin 86 mg, and vincristine 2 mg on day 1; prednisone 100 mg on days 1-5; and lenalidomide 25 mg on days 1-14. The interval between each cycle was 21 d. The patient received a conditioning regimen (busulfan, cyclophosphamide, and etoposide) followed by peripheral blood stem cell infusion. Unfortunately, she developed sustained fever and a low platelet count 17 d after ACST, leading to a diagnosis of HLH after ASCT. During treatment, she experienced thrombocytopenia and Pneumocystis carinii pneumonia. The patient was successfully treated with etoposide and glucocorticoids. CONCLUSION: It is possible that development of HLH is related to immune reconstitution after ASCT.

18.
Bioeng Transl Med ; 8(3): e10505, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37206220

RESUMO

Parkinson's disease (PD) is a common neurodegenerative disease with limited treatment and no cure, hence, broadening PD drug spectrum is of great significance. At present, engineered microorganisms are attracting increasing attention. In this study, we constructed an engineered strain of Clostridium butyricum-GLP-1, a C. butyricum (a probiotic) that consistently expresses glucagon-like peptide-1 (GLP-1, a peptide-based hormone with neurological advantage) in anticipation of its use in PD treatment. We further investigated the neuroprotective mechanism of C. butyricum-GLP-1 on PD mice models induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. The results indicated that C. butyricum-GLP-1 could improve motor dysfunction and ameliorate neuropathological changes by increasing TH expression and reducing the expression of α-syn. Moreover, we confirmed that C. butyricum-GLP-1 improved microbiome imbalance of PD mice by decreasing the relative abundance of Bifidobacterium at the genus level, improved gut integrity, and upregulated the levels of GPR41/43. Surprisingly, we found it could exert its neuroprotective effects via promoting PINK1/Parkin mediated mitophagy and attenuating oxidative stress. Together, our work showed that C. butyricum-GLP-1 improves PD by promoting mitophagy, which provides an alternative therapeutic modality for PD.

19.
Phys Rev E ; 107(2-1): 024218, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36932477

RESUMO

We study the ground-state stability of the trapped one-dimensional Bose-Einstein condensate under a density-dependent gauge field by variational and numerical methods. The competition of density-dependent gauge field and mean-field atomic interaction induces the instability of the ground state, which results in irregular dynamics. The threshold of the gauge field for exciting the instability is obtained analytically and confirmed numerically. When the gauge field is less than the threshold, the system is stable, and the gauge field induces chiral dynamics of the wave packet. When the gauge field is greater than the threshold, the system is unstable, and the ground-state wave packet will be deformed and fragmented. Interestingly, we find that as the gauge field approaches the threshold, strong dipolar and breathing dynamics take place, and strong modes mixing occurs, the instability of the system sets in. In addition, we show that the stability of the system can be well controlled by periodical modulation of the trapping potential. We provide theoretical evidence to understand and control the irregular dynamics associated with chiral superfluid induced by density-dependent gauge field.

20.
Plant Sci ; 329: 111599, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36682585

RESUMO

The enzyme flavone synthase Is (FNS Is) converts flavanones to flavones, whereas flavanone 3ß-hydroxylases (F3Hs) catalyze the formation of dihydroflavonols, a precursor of flavonols and anthocyanins. Canonical F3Hs have been characterized in seed plants, which are evolutionarily related to liverwort FNS Is. However, as important evolutionary lineages between liverworts and seed plants, ferns FNS Is and F3Hs have not been identified. In the present study, we characterized a bifunctional enzyme PnFNS I/F3H from the fern Psilotum nudum. We found that PnFNS I/F3H catalyzed the conversion of naringenin to apigenin and dihydrokaempferol. In addition, it catalyzed five different flavanones to generate the corresponding flavones. Site-directed mutagenesis results indicated that the P228-Y228 mutant protein displayed the FNS I/F2H activity (catalyzing naringenin to generate apigenin and 2-hydroxynaringenin), thus having similar functions as liverwort FNS I/F2H. Moreover, the overexpression of PnFNS I/F3H in Arabidopsis tt6 and dmr6 mutants increased the content of flavones and flavonols in plants, further indicating that PnFNS I/F3H showed FNS I and F3H activities in planta. This is the first study to characterize a bifunctional enzyme FNS I/F3H in ferns. The functional transition from FNS I/F3H to FNS I/F2H will be helpful in further elucidating the relationship between angiosperm F3Hs and liverwort FNS Is.


Assuntos
Gleiquênias , Flavanonas , Flavonas , Apigenina , Antocianinas , Gleiquênias/metabolismo , Oxigenases de Função Mista/metabolismo , Flavonas/metabolismo , Flavanonas/metabolismo , Flavonóis
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