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1.
Bioresour Technol ; : 131497, 2024 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-39299347

RESUMEN

4-hydroxymandelate is a high-value aromatic compound used in the medicine, cosmetics, food, and chemical industry. However, existing natural extraction and chemical synthesis methods are costly and lead to environmental pollution. This study employed metabolic engineering and directed evolution strategies for de novo 4-hydroxymandelate biosynthesis. Two key challenges were addressed: insufficient precursor supply and limited activity of crucial enzymes. Through gene overexpression and multi-level gene interference using CRISPRi, An Escherichia coli chassis capable of producing the key precursor 4-hydroxyphenylpyruvate and the titer reached 5.05 mM (0.91 g/L). A mutant clone was obtained, HmaSV152G, which showed a 5.13-fold improvement in the catalytic rate. During fermentation, a high production of 194.87 mM (32.768 g/L) 4-hydroxymandelate was achieved in 76 h with a batch supply of glucose in a 5-L bioreactor. This study demonstrated the great potential of biosensors in protein engineering and provides a reference for large-scale production of other high-value aromatic compounds.

2.
Discov Oncol ; 15(1): 458, 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39292317

RESUMEN

BACKGROUND: Chondroitin polymerizing factor (CHPF) has been found to be involved in the development of numerous cancers and correlated with poor prognosis. However, its role in the tumorigenesis and development of colorectal cancer (CRC) remains unknown. METHODS: In our research, we explored CHPF expression and clinicopathological characteristics using The Cancer Genome Atlas Program (TCGA), UALCAN, GSE9348, TIMER2.0 and The Human Protein Atlas (HPA) database, in addition, we validated CHPF expression in CRC cell lines by Real-Time Quantitative PCR (qRT-PCR) and Western blot (WB). KM-Plotter, PrognoScan and TCGA were also utilized to verify its prognosis value in CRC. Small-interfer RNA (Si-RNA) was used to perform Cell Counting Kit-8 (CCK8), colony formation, 5-ethynyl-2'-deoxyuridine (EDU), transwell and wound healing assays to testify its function on the tumor progression. Based on TCGA database, we probed potential biological mechanism by which CHPF play its role via clusterProfiler package and GEPIA database and we validated their correlation by WB assay. Moreover, we explored its potential association with the tumor microenvironment (TME), immune infiltrated cells, immune checkpoints, tumor mutation burden (TMB) as well as microsatellite instability (MSI), and investigated immunotherapy sensitivity via Tumor Immune Dysfunction and Exclusion (TIDE) algorithm as well as potentially effective therapeutic drugs via pRRophetic algorithm. RESULTS: CHPF was identified upregulated in CRC tissues and cells, correlated with poor prognosis, and nodal metastasis status, stage and histological subtype. Down-regulation of CHPF inhibited CRC cell proliferation, migration and its expression correlated with wnt pathway key molecules. In addition, high expression of CHPF was positively correlated with TME scores, Regulatory T cells (Tregs) cell infiltration degree, Programmed death-1 (PD-1), MSI-high (MSI-H), and TIDE scores, however, not with TMB. Targeted drug analysis showed that patients with high CHPF expression were more sensitive to telatinib, recaparib, serdemetan, and trametinib. CONCLUSION: CHPF could promote the proliferation and migration of CRC cells and lead to poor prognosis, possibly through wnt pathways as well as changes in TME. Patients with high expression of CHPF had poor efficacy in immunotherapy, which might be related to Tregs cell infiltration. Above all, it might offer more reliable guidance for future immunotherapy.

3.
BMC Vet Res ; 20(1): 390, 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39227948

RESUMEN

BACKGROUND: This study aimed to identify the roles of L-tryptophan (Trp) and its rate-limiting enzymes on the receptivity of bovine endometrial epithelial cells. Real-time PCR was conducted to analyze the differential expression of genes between different groups of bovine endometrial epithelial cells. Western blot was performed to detect Cyclooxygenase-2 (COX2) expression after treatment with Trp or kynurenine (the main metabolites of Trp). The kynurenine assay was used to examine if Trp or prostaglandin E2 (PGE2) can increase the production of kynurenine in the bovine endometrial epithelial cells. RESULTS: Trp significantly stimulates insulin growth factor binding protein 1 (IGFBP1) expression, a common endometrial marker of conceptus elongation and uterus receptivity for ruminants. When bovine endometrial epithelial cells are treated with Trp, tryptophan hydroxylase-1 remains unchanged, but tryptophan 2,3-dioxygenase 2 (TDO2) is significantly increased, suggesting tryptophan is mainly metabolized through the kynurenine pathway. Kynurenine significantly stimulates IGFBP1 expression. Furthermore, Trp and kynurenine significantly increase the expression of aryl hydrocarbon receptor (AHR). CH223191, an AHR inhibitor, abrogates the induction of Trp and kynurenine on IGFBP1. PGE2 significantly induces the expression of TDO2, AHR, and IGFBP1. CONCLUSIONS: The regulation between Trp / kynurenine and PGE2 may be crucial for the receptivity of the bovine uterus.


Asunto(s)
Endometrio , Células Epiteliales , Proteína 1 de Unión a Factor de Crecimiento Similar a la Insulina , Quinurenina , Receptores de Hidrocarburo de Aril , Triptófano Oxigenasa , Triptófano , Animales , Bovinos , Femenino , Triptófano/farmacología , Triptófano/metabolismo , Endometrio/metabolismo , Endometrio/efectos de los fármacos , Células Epiteliales/metabolismo , Células Epiteliales/efectos de los fármacos , Proteína 1 de Unión a Factor de Crecimiento Similar a la Insulina/metabolismo , Proteína 1 de Unión a Factor de Crecimiento Similar a la Insulina/genética , Receptores de Hidrocarburo de Aril/metabolismo , Receptores de Hidrocarburo de Aril/genética , Quinurenina/metabolismo , Quinurenina/farmacología , Triptófano Oxigenasa/metabolismo , Triptófano Oxigenasa/genética , Dinoprostona/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Ciclooxigenasa 2/metabolismo , Ciclooxigenasa 2/genética
4.
ACS Biomater Sci Eng ; 2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39240226

RESUMEN

Bladder tissue engineering offers significant potential for repairing defects resulting from congenital and acquired conditions. However, the effectiveness of engineered grafts is often constrained by insufficient vascularization and neural regeneration. This study utilized four primary biomaterials─gelatin methacryloyl (GelMA), chitin nanocrystals (ChiNC), titanium carbide (MXene), and adipose-derived stem cells (ADSC)─to formulate two types of bioinks, GCM0.2 and GCM0.2-ADSC, in specified proportions. These bioinks were 3D printed onto bladder acellular matrix (BAM) patches to create BAM-GCM0.2 and BAM-GCM0.2-ADSC patches. The BAM-GCM0.2-ADSC patches underwent electrical stimulation to yield GCM0.2-ADSC-ES bladder patches. Employed for the repair of rat bladder defects, these patches were evaluated against a Control group, which underwent partial cystectomy followed by direct suturing. Our findings indicate that the inclusion of ADSC and electrical stimulation significantly enhances the regeneration of rat bladder smooth muscle (from [24.052 ± 2.782] % to [57.380 ± 4.017] %), blood vessels (from [5.326 ± 0.703] % to [12.723 ± 1.440] %), and nerves (from [0.227 ± 0.017] % to [1.369 ± 0.218] %). This research underscores the superior bladder repair capabilities of the GCM0.2-ADSC-ES patch and opens new pathways for bladder defect repair.

5.
Theriogenology ; 229: 16-22, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39142066

RESUMEN

Spermatogenesis in eukaryotes is a process that occurs within a very narrow temperature threshold, typically not exceeding 36 °C. SPO11 was isolated from the temperature-sensitive mutant receptor of Saccharomyces cerevisiae and is thought to be the only protein that functions during meiosis. This suggested that SPO11 may be the key protein that influenced the temperature of spermatogenesis not exceeding 36 °C. Elevated temperatures typically damage the spermatogenic cells. Birds have a core body temperature of 41-42 °C, and their testis are located inside their bodies, providing an alternative perspective to investigate the potential impact of temperature threshold on spermatogenesis. The objective of this study was to ascertain whether elevated ambient temperatures affect spermatogenesis in birds and whether SPO11 is the key gene affecting the temperature threshold for spermatogenesis. STRA8, SCP3, SPO11, γ-H2AX, and RAD51 were all crucial components in the process of meiotic initiation, synapsis, DNA double-strand break (DSB) induction, homologous chromosome crossover recombination, and repair of DSB. In this study, 39-day-old Japanese quail were subjected to heat stress (HS) at 38 °C for 8 h per day for 3 (3d HS) and 13 (13d HS) consecutive days and analyzed the expression of meiotic signaling molecules (STRA8, SCP3, SPO11, γ-H2AX, and RAD51) using molecular biology techniques, including Immunohistochemistry (IHC), Western Blot (WB), and Real-time Quantitative Polymerase Chain Reaction (qRT-PCR). We found that spermatogenesis was normal in both groups exposed to HS. Meiotic signaling molecules were expressed normally in the 3d HS group. All detected signaling molecules were normally expressed in the 13d HS group, except for SPO11, which showed a significant increase in expression, indicating that SPO11 was temperature-sensitive. We examined the localized expression of each meiotic signaling molecule in quail testis, explored the temperature sensitivity of SPO11, and determined that quail testis can undergo normal spermatogenesis at ambient temperatures exceeding 36 °C. This study concluded that SPO11 is not the key protein influencing spermatogenesis in birds. These findings enhance our understanding of avian spermatogenesis.


Asunto(s)
Espermatogénesis , Testículo , Animales , Masculino , Espermatogénesis/fisiología , Testículo/metabolismo , Calor , Profase Meiótica I/fisiología , Coturnix/genética , Coturnix/fisiología , Coturnix/metabolismo , Transducción de Señal , Regulación de la Expresión Génica/fisiología , Meiosis/fisiología
6.
Regen Biomater ; 11: rbae083, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39077683

RESUMEN

Bladder tissue engineering holds promise for addressing bladder defects resulting from congenital or acquired bladder diseases. However, inadequate vascularization significantly impacts the survival and function of engineered tissues after transplantation. Herein, a novel bilayer silk fibroin (BSF) scaffold was fabricated with the capability of vascular endothelial growth factor (VEGF) and platelet derived growth factor-BB (PDGF-BB) sequential release. The outer layer of the scaffold was composed of compact SF film with waterproofness to mimic the serosa of the bladder. The inner layer was constructed of porous SF matrix incorporated with SF microspheres (MS) loaded with VEGF and PDGF-BB. We found that the 5% (w/v) MS-incorporated scaffold exhibited a rapid release of VEGF, whereas the 0.2% (w/v) MS-incorporated scaffold demonstrated a slow and sustained release of PDGF-BB. The BSF scaffold exhibited good biocompatibility and promoted endothelial cell migration, tube formation and enhanced endothelial differentiation of adipose derived stem cells (ADSCs) in vitro. The BSF patch was constructed by seeding ADSCs on the BSF scaffold. After in vivo transplantation, not only could the BSF patch facilitate the regeneration of urothelium and smooth muscle, but more importantly, stimulate the regeneration of blood vessels. This study demonstrated that the BSF patch exhibited excellent vascularization capability in bladder reconstruction and offered a viable functional bioengineered patch for future clinical studies.

7.
J Neural Eng ; 21(3)2024 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-38842111

RESUMEN

Objective. Multi-channel electroencephalogram (EEG) technology in brain-computer interface (BCI) research offers the advantage of enhanced spatial resolution and system performance. However, this also implies that more time is needed in the data processing stage, which is not conducive to the rapid response of BCI. Hence, it is a necessary and challenging task to reduce the number of EEG channels while maintaining decoding effectiveness.Approach. In this paper, we propose a local optimization method based on the Fisher score for within-subject EEG channel selection. Initially, we extract the common spatial pattern characteristics of EEG signals in different bands, calculate Fisher scores for each channel based on these characteristics, and rank them accordingly. Subsequently, we employ a local optimization method to finalize the channel selection.Main results. On the BCI Competition IV Dataset IIa, our method selects an average of 11 channels across four bands, achieving an average accuracy of 79.37%. This represents a 6.52% improvement compared to using the full set of 22 channels. On our self-collected dataset, our method similarly achieves a significant improvement of 24.20% with less than half of the channels, resulting in an average accuracy of 76.95%.Significance. This research explores the importance of channel combinations in channel selection tasks and reveals that appropriately combining channels can further enhance the quality of channel selection. The results indicate that the model selected a small number of channels with higher accuracy in two-class motor imagery EEG classification tasks. Additionally, it improves the portability of BCI systems through channel selection and combinations, offering the potential for the development of portable BCI systems.


Asunto(s)
Interfaces Cerebro-Computador , Electroencefalografía , Imaginación , Electroencefalografía/métodos , Humanos , Imaginación/fisiología , Algoritmos , Movimiento/fisiología
8.
ChemSusChem ; : e202400601, 2024 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-38782717

RESUMEN

The modular structure of small molecular acceptors (SMAs) allows for versatile modifications of the materials and boosts the photovoltaic efficiencies of organic solar cells (OSCs) in recent years. As a critical component, the endcaps of SMAs have been intensively investigated and modified to control the molecular aggregation and photo-electronic conversion. However, most of the studies focus on halogenation or π-fusion extension of the endcap moieties, but overlook the non-fused π-extension approach, which could be a promising strategy to balance the self-aggregation and compatibility behaviors. Herein, we reported two new acceptors namely BTP-Th and BTP-FTh based on non-fused π-extension of the endcap by chlorinated-thiophene, of which the latter molecule has better co-planarity and crystallinity because of the intramolecular noncovalent interactions. Paired with donor PBDB-T, the optimal device of BTP-FTh reveals a greater efficiency of 14.81 % that that of BTP-Th (13.91 %). Nevertheless, the BTP-Th based device realizes a lower energy loss, enabling BTP-Th as a good candidate to serve as guest acceptor. As a result, the ternary solar cells of PM6 : BTP-eC9 : BTP-Th output a champion efficiency up to 18.71 % with enhanced open-circuit voltage. This study highlights the significance of rational decoration of endcaps for the design of high-performance SMAs and photovoltaic cells.

9.
Front Endocrinol (Lausanne) ; 15: 1356914, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38752181

RESUMEN

Introduction: Nutritional deficiency occurs frequently during pregnancy and breastfeeding. Tryptophan (Trp), an essential amino acid which is critical for protein synthesis, serves as the precursor for serotonin, melatonin, and kynurenine (Kyn). The imbalance between serotonin and kynurenine pathways in Trp metabolism is closely related to inflammation and depression. This study assessed the effects of Trp deficiency on mouse early pregnancy. Methods: Embryo implantation and decidualization were analyzed after female mice had been fed diets containing 0.2% Trp (for the control group), 0.062% Trp (for the low Trp group) and 0% Trp (for the Trp-free group) for two months. The uteri of the mice were collected on days 4, 5, and 8 of pregnancy for further analysis. Results: On day 8 of pregnancy, the number of implantation sites were found to be similar between the control and the low Trp groups. However, no implantation sites were detected in the Trp-free group. On day 5 of pregnancy, plane polarity- and decidualization-related molecules showed abnormal expression pattern in the Trp-free group. On day 4 of pregnancy, there was no significant difference in uterine receptivity molecules between the low-Trp group and the control group, but uterine receptivity was abnormal in the Trp-free group. At implantation sites of the Trp-free group, IDO and AHR levels were markedly elevated. This potentially increased levels of Kyn, 2-hydroxy estradiol, and 4-hydroxy estradiol to affect decidualization. Conclusions: Trp-free diet may impair decidualization via the IDO-KYN-AHR pathway.


Asunto(s)
Decidua , Implantación del Embrión , Triptófano , Animales , Femenino , Implantación del Embrión/fisiología , Implantación del Embrión/efectos de los fármacos , Triptófano/metabolismo , Ratones , Embarazo , Decidua/metabolismo , Dieta , Quinurenina/metabolismo
10.
J Agric Food Chem ; 2024 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-38606577

RESUMEN

Flammulina velutipes, a popular edible mushroom, contains sesquiterpenes with potential health benefits. We characterized 12 sesquiterpene synthases and one P450 enzyme in F. velutipes using Aspergillus oryzae as a heterologous expression system, culminating in the biosynthesis of 16 distinct sesquiterpene compounds. An enzyme encoded by the axeB gene responsible for the synthesis of the spiro [4.5] decane compound axenol was discovered, and the mechanism of spirocycle formation was elucidated through quantum mechanical calculations. Furthermore, we delineated the role of a P450 enzyme colocated with AxeB in producing the novel compound 3-oxo-axenol. Our findings highlight the diverse array of sesquiterpene skeletons and functional groups biosynthesized by these enzymes in F. velutipes and underscore the effectiveness of the A. oryzae system as a heterologous host for expressing genes in the Basidiomycota genome. These insights into the biosynthesis of bioactive compounds in F. velutipes have significant implications for functional food and drug development.

11.
Appl Microbiol Biotechnol ; 108(1): 275, 2024 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-38530470

RESUMEN

Prenylation plays a pivotal role in the diversification and biological activities of natural products. This study presents the functional characterization of TolF, a multiple prenyltransferase from Tolypocladium inflatum. The heterologous expression of tolF in Aspergillus oryzae, coupled with feeding the transformed strain with paxilline, resulted in the production of 20- and 22-prenylpaxilline. Additionally, TolF demonstrated the ability to prenylated the reduced form of paxilline, ß-paxitriol. A related prenyltransferase TerF from Chaunopycnis alba, exhibited similar substrate tolerance and regioselectivity. In vitro enzyme assays using purified recombinant enzymes TolF and TerF confirmed their capacity to catalyze prenylation of paxilline, ß-paxitriol, and terpendole I. Based on previous reports, terpendole I should be considered a native substrate. This work not only enhances our understanding of the molecular basis and product diversity of prenylation reactions in indole diterpene biosynthesis, but also provides insights into the potential of fungal indole diterpene prenyltransferase to alter their position specificities for prenylation. This could be applicable for the synthesis of industrially useful compounds, including bioactive compounds, thereby opening up new avenues for the development of novel biosynthetic strategies and pharmaceuticals. KEY POINTS: • The study characterizes TolF as a multiple prenyltransferase from Tolypocladium inflatum. • TerF from Chaunopycnis alba shows similar substrate tolerance and regioselectivity compared to TolF. • The research offers insights into the potential applications of fungal indole diterpene prenyltransferases.


Asunto(s)
Dimetilaliltranstransferasa , Diterpenos , Hypocreales , Dimetilaliltranstransferasa/metabolismo , Prenilación , Indoles/metabolismo , Diterpenos/metabolismo , Especificidad por Sustrato
12.
Inflammopharmacology ; 32(3): 1887-1901, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38526770

RESUMEN

Sepsis, a life-threatening condition characterized by dysregulated immune responses, remains a significant clinical challenge. Myricanol, a natural compound, plays a variety of roles in regulating lipid metabolism, anti-cancer, anti-neurodegeneration, and it could act as an Sirtuin 1 (SIRT1) activator. This study aimed to explore the therapeutic potential and underlying mechanism of myricanol in the lipopolysaccharide (LPS)-induced sepsis model. In vivo studies revealed that myricanol administration significantly improved the survival rate of LPS-treated mice, effectively mitigating LPS-induced inflammatory responses in lung tissue. Furthermore, in vitro studies demonstrated that myricanol treatment inhibited the expression of pro-inflammatory cytokines, attenuated signal pathway activation, and reduced oxidative stress in macrophages. In addition, we demonstrated that myricanol selectively enhances SIRT1 activation in LPS-stimulated macrophages, and all of the protective effect of myricanol were reversed through SIRT1 silencing. Remarkably, the beneficial effects of myricanol against LPS-induced sepsis were abolished in SIRT1 myeloid-specific knockout mice, underpinning the critical role of SIRT1 in mediating myricanol's therapeutic efficacy. In summary, this study provides significant evidence that myricanol acts as a potent SIRT1 activator, targeting inflammatory signal pathways and oxidative stress to suppress excessive inflammatory responses. Our findings highlight the potential of myricanol as a novel therapeutic agent for the treatment of LPS-induced sepsis.


Asunto(s)
Inflamación , Lipopolisacáridos , Ratones Endogámicos C57BL , Ratones Noqueados , Factor 2 Relacionado con NF-E2 , FN-kappa B , Sepsis , Transducción de Señal , Sirtuina 1 , Regulación hacia Arriba , Animales , Masculino , Ratones , Antiinflamatorios/farmacología , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Lipopolisacáridos/farmacología , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Factor 2 Relacionado con NF-E2/efectos de los fármacos , Factor 2 Relacionado con NF-E2/metabolismo , FN-kappa B/efectos de los fármacos , FN-kappa B/metabolismo , Estrés Oxidativo/efectos de los fármacos , Células RAW 264.7 , Sepsis/tratamiento farmacológico , Sepsis/metabolismo , Transducción de Señal/efectos de los fármacos , Sirtuina 1/efectos de los fármacos , Sirtuina 1/metabolismo , Regulación hacia Arriba/efectos de los fármacos
13.
ACS Nano ; 2024 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-38345022

RESUMEN

The design of bio-responsive functional molecular materials that can undergo self-assembly to form nanostructures within cells in response to cellular endogenous stimuli and the clarification of their prospective reaction mechanisms are of paramount significance. This work aims to elucidate the spatiotemporal generation of subcellular nanostructures and their influence on cellular functionality. Three sets of cyclometalated platinum complexes have been designed and synthesized as near-infrared phosphorescent turn-on probes for specific anions based on dynamic self-assembly in aqueous solution. The augmentation of the quantity of aromatic rings in the NN bidentate ligand of the complex modifies both the intensity of the intermolecular Pt-Pt interaction and the capacity to generate self-assembled nanowires with near-infrared emission. Besides, we explored the impact of the CN ligand's substituent effect on anion recognition, which revealed that complexes with electron-absorbing F atom substitution exhibit superior selectivity for Br-. These complexes display vivid green turn-on luminescence upon interaction with cellular biomolecules, enabling dynamic monitoring of their subcellular distribution and their interaction on diverse conditions. Furthermore, our complexes were observed to induce oncosis in cancer cells, underscoring the potential of our work in facilitating in vitro diagnosis and developing effective theranostic agents for cancer therapy.

14.
Int J Mol Sci ; 25(3)2024 Jan 26.
Artículo en Inglés | MEDLINE | ID: mdl-38338812

RESUMEN

Biosensors based on allosteric transcription factors have been widely used in synthetic biology. In this study, we utilized the Acinetobacter ADP1 transcription factor PobR to develop a biosensor activating the PpobA promoter when bound to its natural ligand, 4-hydroxybenzoic acid (4HB). To screen for PobR mutants responsive to 4-hydroxyphenylpyruvate(HPP), we developed a dual selection system in E. coli. The positive selection of this system was used to enrich PobR mutants that identified the required ligands. The following negative selection eliminated or weakened PobR mutants that still responded to 4HB. Directed evolution of the PobR library resulted in a variant where PobRW177R was 5.1 times more reactive to 4-hydroxyphenylpyruvate than PobRWT. Overall, we developed an efficient dual selection system for directed evolution of biosensors.


Asunto(s)
Técnicas Biosensibles , Ácidos Fenilpirúvicos , Transactivadores , Transactivadores/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Factores de Transcripción/metabolismo
15.
Phytother Res ; 38(4): 1783-1798, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38323338

RESUMEN

Macrophage inflammation plays a central role during the development and progression of sepsis, while the regulation of macrophages by parthanatos has been recently identified as a novel strategy for anti-inflammatory therapies. This study was designed to investigate the therapeutic potential and mechanism of pimpinellin against LPS-induced sepsis. PARP1 and PAR activation were detected by western blot or immunohistochemistry. Cell death was assessed by flow cytometry and western blot. Cell metabolism was measured with a Seahorse XFe24 extracellular flux analyzer. C57, PARP1 knockout, and PARP1 conditional knock-in mice were used in a model of sepsis caused by LPS to assess the effect of pimpinellin. Here, we found that pimpinellin can specifically inhibit LPS-induced macrophage PARP1 and PAR activation. In vitro studies showed that pimpinellin could inhibit the expression of inflammatory cytokines and signal pathway activation in macrophages by inhibiting overexpression of PARP1. In addition, pimpinellin increased the survival rate of LPS-treated mice, thereby preventing LPS-induced sepsis. Further research confirmed that LPS-induced sepsis in PARP1 overexpressing mice was attenuated by pimpinellin, and PARP1 knockdown abolished the protective effect of pimpinellin against LPS-induced sepsis. Further study found that pimpinellin can promote ubiquitin-mediated degradation of PARP1 through RNF146. This is the first study to demonstrate that pimpinellin inhibits excessive inflammatory responses by promoting the ubiquitin-mediated degradation of PARP1.


Asunto(s)
Lipopolisacáridos , Metoxaleno , Sepsis , Animales , Ratones , Inflamación/metabolismo , Macrófagos , Metoxaleno/análogos & derivados , Ratones Endogámicos C57BL , Sepsis/inducido químicamente , Sepsis/tratamiento farmacológico , Ubiquitinación , Ubiquitinas/metabolismo
16.
J Fungi (Basel) ; 10(1)2024 Jan 03.
Artículo en Inglés | MEDLINE | ID: mdl-38248944

RESUMEN

For more than a thousand years, Aspergillus oryzae has been used in traditional culinary industries, including for food fermentation, brewing, and flavoring. In recent years, A. oryzae has been extensively used in deciphering the pathways of natural product synthesis and value-added compound bioproduction. Moreover, it is increasingly being used in modern biotechnology industries, such as for the production of enzymes and recombinant proteins. The investigation of A. oryzae has been significantly accelerated through the successive application of a diverse array of synthetic biology techniques and methodologies. In this review, the advancements in biological tools for the synthesis of A. oryzae, including DNA assembly technologies, gene expression regulatory elements, and genome editing systems, are discussed. Additionally, the challenges associated with the heterologous expression of A. oryzae are addressed.

17.
Artículo en Inglés | MEDLINE | ID: mdl-38082969

RESUMEN

Facial stimulation can produce specific event-related potential (ERP) component N170 in the fusiform gyrus region. However, the role of the fusiform gyrus region in facial preference tasks is not clear at present, and the current research of facial preference analysis based on EEG signals is mostly carried out in the scalp domain. This paper explores whether the region of the fusiform gyrus is involved in processing face preference emotions in terms of the distribution of energy over the source domain, and finds that the pars orbitalis cortex is most energetically active in the face preference task and that there are significant differences between the left and right hemispheres.Clinical Relevance- The role of pars orbitalis in facial preference may help doctors determine whether the pars orbitalis cortex is lost in clinical practice.


Asunto(s)
Electroencefalografía , Potenciales Evocados , Potenciales Evocados/fisiología , Corteza Cerebral , Lóbulo Temporal/fisiología , Emociones/fisiología
18.
Artículo en Inglés | MEDLINE | ID: mdl-38083718

RESUMEN

Steady-state visual evoked potential (SSVEP) is one of the main paradigms of brain-computer interface (BCI). However, the acquisition method of SSVEP can cause subject fatigue and discomfort, leading to the insufficiency of SSVEP databases. Inspired by generative determinantal point process (GDPP), we utilize the determinantal point process in generative adversarial network (GAN) to generate SSVEP signals. We investigate the ability of the method to synthesize signals from the Benchmark dataset. We further use some evaluation metrics to verify its validity. Results prove that the usage of this method significantly improved the authenticity of generated data and the accuracy (97.636%) of classification using deep learning in SSVEP data augmentation.


Asunto(s)
Interfaces Cerebro-Computador , Potenciales Evocados Visuales , Electroencefalografía/métodos , Estimulación Luminosa/métodos , Bases de Datos Factuales
19.
Am J Reprod Immunol ; 90(5): e13793, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37881124

RESUMEN

RESEARCH QUESTION: Decidualization is critical to the establishment of mouse normal pregnancy. The fibroblast-like stromal cells in the process form polyploid multinucleated cells. Aurora kinase B (Aurora B) has previously been shown to regulate polyploidy in various cells. However, whether Aurora B regulates the formation of decidual cell polyploidization and its regulatory mechanisms remain poorly understood. DESIGN: Establish decidualization model of mouse primary endometrial stromal cells in vitro. Construct pseudopregnancy mouse models and delayed-activation mouse models. Detect Aurora B and polyploidization related genes in mouse uteri treated by Aurora B specific inhibitor Barasertib and CPT. RESULTS: In this study, we found that Aurora B was strongly expressed in endometrial stromal cells after implantation. Additionally, Aurora B was remarkably up regulated in the stromal cells of oil-induced deciduomoa and in vitro decidualization. As an Aurora B specific inhibitor, Barasertib significantly inhibits the mRNA expression of Prl8a2, a marker of mouse decidualization. Furthermore, the protein levels of p-Plk1, Survivin and p-Cdk1 were inhibited by Barasertib. CPT-induced DNA damage suppressed Aurkb (encodes Aurora B) expression, thus resulting in polyploidization. CONCLUSION: Our data shows that Aurora B is expressed in decidual stromal cells of implantation sites and plays a key role for mouse decidualization. The protein of Plk1, Survivn, and Cdk1 may participate in formation of decidual cell polyploidization during mouse decidualization.


Asunto(s)
Aurora Quinasa B , Decidua , Útero , Animales , Femenino , Ratones , Embarazo , Aurora Quinasa B/metabolismo , Decidua/metabolismo , Implantación del Embrión/fisiología , Poliploidía , Células del Estroma/metabolismo , Útero/metabolismo
20.
J Med Chem ; 66(18): 13103-13115, 2023 09 28.
Artículo en Inglés | MEDLINE | ID: mdl-37724909

RESUMEN

Herein, four planar cyclometalated platinum(II) complexes with a main ligand of enlarged aromatic rings have been assessed as effective anticancer theranostic agents for the first time. With an increased number of aromatic rings in the N∧N ligand, 1a-1d exhibit increased lipophilicity and cytotoxicity selectivity. The intensity of the Pt-Pt interaction of each complex can be indicated by an enhanced near-infrared (NIR) emission in phosphate-buffered saline (PBS), their binding activity with biomolecules of bovine serum albumin (BSA) is accompanied by a vivid turn-on green emission, and the intensity gradually decreased from 1a to 1d, which is consistent with the docking of two complexes with BSA. Both "turn-on" NIR and green emission of 1d can be mainly observed in nuclei of living cell within 24 h, while two phosphorescence traces of 1b were recorded in lysosomes by confocal imaging. Moreover, 1d shows the highest efficiency in inducing oncosis of Hela cells, and the relative process was investigated.


Asunto(s)
Antineoplásicos , Platino (Metal) , Humanos , Células HeLa , Ligandos , Medicina de Precisión , Antineoplásicos/farmacología , Albúmina Sérica Bovina
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