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1.
Molecules ; 29(6)2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38542825

RESUMO

Roasting is an important step in the pretreatment of biomass upgrading. Roasting can improve the fuel quality of biomass, reduce the O/C and H/C ratios in the biomass, and provide the biomass with a fuel quality comparable to that of lignite. Therefore, studying the structure and component evolution laws during biomass roasting treatment is important for the rational and efficient utilization of biomass. When the roasting temperature is 200-300 °C, the cellulose and hemicellulose in the biomass undergo a depolymerization reaction, releasing many monocyclic aromatic hydrocarbons with high reactivity. The proportion of monocyclic aromatic hydrocarbons in biomass roasting products can be effectively regulated by controlling the reaction temperature, residence time, catalyst, baking atmosphere, and other factors in the biomass roasting process. This paper focuses on the dissociation law of organic components in the pretreatment process of biomass roasting.


Assuntos
Temperatura Alta , Hidrocarbonetos Aromáticos , Biomassa , Hidrocarbonetos Aromáticos/química , Temperatura , Celulose , Hidrocarbonetos
2.
PLoS One ; 19(3): e0295536, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38466697

RESUMO

Brain extraction is an important prerequisite for the automated diagnosis of intracranial lesions and determines, to a certain extent, the accuracy of subsequent lesion identification, localization, and segmentation. To address the problem that the current traditional image segmentation methods are fast in extraction but poor in robustness, while the Full Convolutional Neural Network (FCN) is robust and accurate but relatively slow in extraction, this paper proposes an adaptive mask-based brain extraction method, namely AMBBEM, to achieve brain extraction better. The method first uses threshold segmentation, median filtering, and closed operations for segmentation, generates a mask for the first time, then combines the ResNet50 model, region growing algorithm, and image properties analysis to further segment the mask, and finally complete brain extraction by multiplying the original image and the mask. The algorithm was tested on 22 test sets containing different lesions, and the results showed MPA = 0.9963, MIoU = 0.9924, and MBF = 0.9914, which were equivalent to the extraction effect of the Deeplabv3+ model. However, the method can complete brain extraction of approximately 6.16 head CT images in 1 second, much faster than Deeplabv3+, U-net, and SegNet models. In summary, this method can achieve accurate brain extraction from head CT images more quickly, creating good conditions for subsequent brain volume measurement and feature extraction of intracranial lesions.


Assuntos
Encéfalo , Cabeça , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Redes Neurais de Computação , Algoritmos , Processamento de Imagem Assistida por Computador/métodos , Tomografia Computadorizada por Raios X/métodos
3.
Chemphyschem ; : e202300912, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38369921

RESUMO

The enclosed space within fullerene molecules, capable of trapping metal clusters, offers an opportunity to investigate the behavior of metal atoms in a highly confined sub-nanometer environment. However, the studies on trimetallofullerenes M3@C80 have been very limited due to their difficult obtainability. In this paper, we present a new method for obtaining a tri-metallofullerene Er3@C80 through exohedral modification of the fullerene cage. Our findings reveal that Er3@C80 exhibits a radical character and can react with the dichlorobenzene radical to generate a stable derivative Er3@C80PhCl2. Theoretical calculations demonstrate the presence of a three-center two-electron metal-metal bond in the center of the fullerene cage. This bond serves to counterbalance the Coulomb repulsion between the Er ions. Consequently, both exohedral derivatization and endohedral three-center bonding contribute to the substantial stability of Er3@C80PhCl2. Furthermore, molecular dynamics simulations indicate that the Er3 cluster within the molecule possesses a rigid triangle structure. The availability of M3@C80 derivatives opens avenues for future investigations into interactions among metal atoms, such as magnetic coupling, within fullerene cages.

4.
Front Microbiol ; 15: 1342705, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38374921

RESUMO

Microbial-based therapies are one of the hotspots in the field of ulcerative colitis research. The lactic acid bacteria and their postbiotics occupy a key position in microbial therapies, however, the mechanism by which they alleviate ulcerative colitis in mice is unknown. We investigated the effects of Lacticaseibacillus rhamnosus 2016SWU.05.0601 (Lr-0601) and its postbiotics on male Kunming mice with dextran sulfate sodium salt (DSS)-induced ulcerative colitis (UC). The results showed that Lr-0601 significantly alleviated the deterioration of UC and restored the expression of intestinal mechanical barrier proteins. In addition, Lr-0601 significantly reduced the expression of inflammatory cytokines in the body and regulated the expression of key regulatory genes of the NF-κB-iNOS/COX-2 signaling pathway in colon tissues to a large extent. Our results suggest that supplementation with Lr-0601 and its postbiotics can effectively prevent DSS-induced UC and have a beneficial effect on intestinal health, which also provides new insights and research bases for the prevention as well as the treatment of ulcerative colitis and other diseases related to intestinal barrier dysfunction and other diseases.

5.
Int Immunopharmacol ; 128: 111441, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38171056

RESUMO

Many studies have shown that liver metastasis can weaken the efficacy of immunotherapy. Immunotherapy combined with radiotherapy or anti-angiogenic therapy has been proven to have synergistic anti-tumor effects. So we devote to explore whether the combination of the three therapies can exert effective anti-tumor effects on liver metastasis. The clinical information of 118 patients with liver metastasis were collected to compare the intrahepatic progression-free survival between immunotherapy and immunotherapy combined with other treatments. We used Lewis lung cancer (LLC) cell to establish a mouse liver metastasis tumor model and record tumor burden and survival. Tumor-infiltrating immune cells detected by flow cytometry. RNA sequencing was performed and the proportion of immune cells were analyzed by TIMER2.0 database. Compared with immunotherapy group, the combination therapy group showed a trend for longer median intrahepatic progression-free survival. Radiotherapy combined with PD-1 inhibitor and Anlotinib can inhibit liver metastasis and subcutaneous tumor growth and prolong the survival compared with other groups in vivo. Compared with the anti-PD-1 treatment group, triple therapy can increase CD4+T, CD8+T, and IFN-γ+CD8+T cells and decrease infiltration of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC) in tumors. PPAR signaling pathway were significantly activated and CD8+T and dendritic cells (DC) were increased in the triple therapy group compared to the PD-1 inhibitor combined with Anlotinib group. Radiotherapy combined with PD-1 inhibitor and Anlotinib can effectively exert anti-tumor efficacy and reshape the tumor immune microenvironment by increasing the infiltration of anti-tumor immune cells and reducing the infiltration of immunosuppressive immune cells.


Assuntos
Indóis , Neoplasias Hepáticas , Neoplasias Pulmonares , Quinolinas , Camundongos , Animais , Humanos , Inibidores de Checkpoint Imunológico/farmacologia , Imunoterapia , Microambiente Tumoral , Linhagem Celular Tumoral , Linfócitos T CD8-Positivos
7.
Stud Health Technol Inform ; 310: 674-678, 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38269894

RESUMO

As COVID-19 ravages the world, social media analytics could augment traditional surveys in assessing how the pandemic evolves and capturing consumer chatter that could help healthcare agencies in addressing it. This typically involves mining disclosure events that mention testing positive for the disease or discussions surrounding perceptions and beliefs in preventative or treatment options. The 2020 shared task on COVID-19 event extraction (conducted as part of the W-NUT workshop during the EMNLP conference) introduced a new Twitter dataset for benchmarking event extraction from COVID-19 tweets. In this paper, we cast the problem of event extraction as extractive question answering using recent advances in continuous prompting in language models. On the shared task test dataset, our approach leads to over 5% absolute micro-averaged F1-score improvement over prior best results, across all COVID-19 event slots. Our ablation study shows that continuous prompts have a major impact on the eventual performance.


Assuntos
COVID-19 , Mídias Sociais , Humanos , Benchmarking , Revelação , Instalações de Saúde
8.
J Dairy Sci ; 107(2): 742-758, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37709033

RESUMO

Lactic acid bacteria (LAB), a type of microorganism widely used in functional foods, has gained notable research attention in recent years. Certain strains possess the proteolytic ability to release potentially antihypertensive peptides from dairy proteins, which prompted us to explore the LAB strains from an understudied and unique ingredient, Daqu. We screened for 67 strains of LAB strains from traditional Daqu using the calcium dissolution ring method. Sixteen strains exhibiting angiotensin-converting enzyme inhibition (ACE-I) activity exceeding 50% were chosen for 16S rDNA sequencing and safety assessment. It is noteworthy that Enterococcus faecium CP640 and Lacticaseibacillus rhamnosus CP658 exhibited significant ACE-I activity, which was the result of strain fermentation in reconstituted skim milk. These 2 strains did not exhibit hemolytic activity or antibiotic resistance. They also did not produce biogenic amines and showed high survival rates in the gastrointestinal tract. Additionally, Enterococcus faecium CP640 and Lacticaseibacillus rhamnosus CP658 fermented milk exhibited a notable reduction in blood pressure levels in spontaneously hypertensive rats (SHR) compared with negative controls in SHR. Importantly, no adverse effect was observed in normal Wistar-Kyoto rats. Through the analysis of physiological, serum, and urine-related indicators, it was observed that Enterococcus faecium CP640 and Lacticaseibacillus rhamnosus CP658 have the potential to promote weight gain in SHR, alleviate excessive heart rate, improve renal function indicators, and effectively regulate blood sugar and uric acid levels in SHR. These 2 strains showed optimal properties in lowering blood pressure and have the potential to be used in functional dairy products in the future.


Assuntos
Enterococcus faecium , Hipertensão , Lacticaseibacillus rhamnosus , Lactobacillales , Animais , Ratos , Anti-Hipertensivos/análise , Fermentação , Hipertensão/tratamento farmacológico , Hipertensão/veterinária , Leite/química , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY
9.
Adv Sci (Weinh) ; 11(6): e2307593, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38151904

RESUMO

Circularly polarized light (CPL) detection has wide applications in many fields, where the anisotropy factor (gIph ) is an important indicator to characterize the CPL detection performance. So far, many materials with high gIph have been reported, however, the exploration of the regulation of gIph is still in its infancy. Herein, two novel alternating chiral-achiral cations intercalation-type chiral hybrid perovskites (CHPs), named (R/S-1-phenylpropylamine)(propylamine)PbBr4 (1-R/S), exhibit above room-temperature (RT) polar-phase transition, which greatly regulates the gIph value. The gIph of 1-R is 0.04 in high-temperature phase chiral non-polar (P21 21 21 ) by applying 5 V bias, interestingly, with the temperature decrease, the gIph value in low-temperature phase chiral polar (P21 ) gradually increases (0.22@360K, 0.40@340K, 0.47@320K), and finally reaches a maximum of 0.5 at RT. Such value is not only the highest among 2D CHPs to date, but presents a 12.5-fold amplification compared with 0.04. Further, this rare phenomenon should be attributed to the built-in electric field induced by the polar photovoltaic effect, which sheds light on further obtaining CHPs with large gIph .

11.
Heliyon ; 9(12): e22875, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38094055

RESUMO

Listeria monocytogenes, is a Gram-positive facultative intracellular bacterium without spores. It can cause invasive diseases such as septicemia, meningitis, and encephalitis, and has a high mortality rate. This is a report on a recent case of neurolisteriosis isolated from cerebrospinal fluid sample of a patient with diabetes and chronic heart failure in our hospital. The patient initially received the combined treatment of cephalosporin and meropenem (both 1.0 g every 8 hours). We identified the pathogenic organism as L. monocytogenes using three identification methods: mass spectrometry, biochemical assays, and molecular techniques. After determining the pathogenic bacteria, we quickly informed the clinician and suggesting a change in antibiotic treatment and immediately discontinued cephalosporin and meropenem. The patient's symptoms were significantly improved after 9 days of penicillin G treatment, and the patient chose to be discharged for personal reasons. In conclusion, certain strains of wild-type Listeria monocytogenes can lead to identification errors that occur across platforms and methods.

12.
Small ; : e2306795, 2023 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-38095535

RESUMO

The formation of carbonate in neutral/alkaline solutions leads to carbonate crossover, severely reducing carbon dioxide (CO2 ) single pass conversion efficiency (SPCE). Thus, CO2 electrolysis is a prospective route to achieve high CO2 utilization under acidic environment. Bimetallic Bi-based catalysts obtained utilizing metal doping strategies exhibit enhanced CO2 -to-formic acid (HCOOH) selectivity in alkaline/neutral media. However, achieving high HCOOH selectivity remains challenging in acidic media. To this end, Indium (In) doped Bi2O2CO3 via hydrothermal method is prepared for in-situ electroreduction to In-Bi/BiOx nanosheets for acidic CO2 reduction reaction (CO2RR). In doping strategy regulates the electronic structure of Bi, promoting the fast derivatization of Bi2O2CO3 into Bi-O active sites to enhance CO2RR catalytic activity. The optimized Bi2 O2 CO3 -derived catalyst achieves the maximum HCOOH faradaic efficiency (FE) of 96% at 200 mA cm-2 . The SPCE for HCOOH production in acid is up to 36.6%, 2.2-fold higher than the best reported catalysts in alkaline environment. Furthermore, in situ Raman and X-ray photoelectron spectroscopy demonstrate that In-induced electronic structure modulation promotes a rapid structural evolution from nanobulks to Bi/BiOx nanosheets with more active species under acidic CO2 RR, which is a major factor in performance improvement.

13.
Mater Today Bio ; 23: 100887, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38144518

RESUMO

Osteosarcoma (OS) is the third most common malignancy in adolescence. Currently, the treatments of OS confront great obstacles of tumor recurrence and critical bone defects after surgery, severely affecting the survival rates and living qualities of patients. Hence, it is urged to develop distinct biomaterials with both efficient tumor therapeutic and osteogenic functions. Although photothermal therapy (PTT) has aroused expanding interest, characterizing negligible invasiveness and high spatiotemporal adjustment, few studies discussed its drawbacks, such as thermal injury to adjacent normal tissue and exceeded laser power density, implying that focusing on sensitizing OS to PTT instead of simply elevating the laser power density may be a fresh way to enhance the PTT efficacy and attenuate the side/adverse effects. Herein, we successfully constructed 3D-printing silicene bioactive glass scaffolds with preferable PTT efficacy at the second near-infrared (NIR-II) biowindow and outstanding osteogenic biofunctions owing to the release of bioactive elements during degradation. Impressively, a histone demethylase inhibitor, IOX1, was introduced before PTT to sensitize OS to thermal therapy and minimize the side/adverse effects. This work offered a distinctive paradigm for optimizing the PTT efficacy of osteogenic scaffolds against OS with epigenetic modulation agents.

14.
J Virol ; 97(12): e0137623, 2023 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-37991368

RESUMO

IMPORTANCE: Rotavirus (RV) is an important zoonosis virus, which can cause severe diarrhea and extra-intestinal infection. To date, some proteins or carbohydrates have been shown to participate in the attachment or internalization of RV, including HGBAs, Hsc70, and integrins. This study attempted to indicate whether there were other proteins that would participate in the entry of RV; thus, the RV VP4-interacting proteins were identified by proximity labeling. After analysis and verification, it was found that VIM and ACTR2 could significantly promote the proliferation of RV in intestinal cells. Through further viral binding assays after knockdown, antibody blocking, and recombinant protein overexpression, it was revealed that both VIM and ACTR2 could promote RV replication.


Assuntos
Proteína 2 Relacionada a Actina , Proteínas do Capsídeo , Mapas de Interação de Proteínas , Rotavirus , Vimentina , Animais , Humanos , Proteína 2 Relacionada a Actina/genética , Proteína 2 Relacionada a Actina/metabolismo , Proteínas do Capsídeo/metabolismo , Intestinos/citologia , Rotavirus/química , Rotavirus/metabolismo , Vimentina/genética , Vimentina/metabolismo , Internalização do Vírus , Replicação Viral , Ligação Proteica
15.
Math Biosci Eng ; 20(8): 14222-14240, 2023 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-37679133

RESUMO

Possible complications, such as intestinal obstruction and inflammation of the intestinal tract, can have a detrimental effect on the prognosis after surgery for Hirschsprung disease. The aim of this study was to investigate the potential targets and mechanisms of action of echinacoside to improve the prognosis of Hirschsprung disease. Genes related to the disease were obtained through analysis of the GSE96854 dataset and four databases: OMIM, DisGeNET, Genecard and NCBI. The targets of echinacoside were obtained from three databases: PharmMapper, Drugbank and TargetNet. The intersection of disease genes and drug targets was validated by molecular docking. The valid docked targets were further explored for their expression by using immunohistochemistry. In this study, enrichment analysis was used to explore the mechanistic pathways involved in the genes. Finally, we identified CA1, CA2, CA9, CA12, DNMT1, RIMS2, RPGRIP1L and ZEB2 as the core targets. Except for ZEB2, which is predominantly expressed in brain tissue, the remaining seven genes show tissue specificity and high expression in the gastrointestinal tract. RIMS2 possesses a high mutation phenomenon in pan-cancer, while a validated ceRNA network of eight genes was constructed. The core genes are involved in several signaling pathways, including the one-carbon metabolic process, carbonate dehydratase activity and others. This study may help us to further understand the pharmacological mechanisms of echinacoside and provide new guidance and ideas to guide the treatment of Hirschsprung disease.


Assuntos
Doença de Hirschsprung , Humanos , Doença de Hirschsprung/tratamento farmacológico , Doença de Hirschsprung/genética , Pós , Simulação de Acoplamento Molecular , Glicosídeos/farmacologia , Glicosídeos/uso terapêutico
16.
BMC Med Imaging ; 23(1): 124, 2023 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-37700250

RESUMO

BACKGROUND: Brain extraction is an essential prerequisite for the automated diagnosis of intracranial lesions and determines, to a certain extent, the accuracy of subsequent lesion recognition, location, and segmentation. Segmentation using a fully convolutional neural network (FCN) yields high accuracy but a relatively slow extraction speed. METHODS: This paper proposes an integrated algorithm, FABEM, to address the above issues. This method first uses threshold segmentation, closed operation, convolutional neural network (CNN), and image filling to generate a specific mask. Then, it detects the number of connected regions of the mask. If the number of connected regions equals 1, the extraction is done by directly multiplying with the original image. Otherwise, the mask was further segmented using the region growth method for original images with single-region brain distribution. Conversely, for images with multi-region brain distribution, Deeplabv3 + is used to adjust the mask. Finally, the mask is multiplied with the original image to complete the extraction. RESULTS: The algorithm and 5 FCN models were tested on 24 datasets containing different lesions, and the algorithm's performance showed MPA = 0.9968, MIoU = 0.9936, and MBF = 0.9963, comparable to the Deeplabv3+. Still, its extraction speed is much faster than the Deeplabv3+. It can complete the brain extraction of a head CT image in about 0.43 s, about 3.8 times that of the Deeplabv3+. CONCLUSION: Thus, this method can achieve accurate brain extraction from head CT images faster, creating a good basis for subsequent brain volume measurement and feature extraction of intracranial lesions.


Assuntos
Algoritmos , Encéfalo , Humanos , Encéfalo/diagnóstico por imagem , Redes Neurais de Computação , Tomografia Computadorizada por Raios X
17.
Small ; 19(44): e2302575, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37394717

RESUMO

Osteosarcoma (OS) is the most frequent osseous neoplasm among young people aged 10-20. Currently, the leading treatment for osteosarcoma is a combination of surgery and chemotherapy. However, the mortality remains high due to chemoresistance, metastasis, and recurrence, attributing to the existence of cancer stem cells (CSCs) as reported. To target CSCs, differentiation therapy attracts increasing attention, inducing CSCs to bulk tumor cells with elevated reactive oxygen species (ROS) levels and less chemoresistance. Moreover, increasing studies have implied that ferroptosis is a promising approach to eliminating cancer cells through eliciting oxidative damage and subsequent apoptosis, effectively bypassing chemoresistance. Here, a cancer-cell-membrane-decorated biocompatible formulation (GA-Fe@CMRALi liposome) is constructed to combat OS efficiently by combining distinct differentiation and ferroptosis therapies through magnified ROS-triggered ferroptosis and apoptosis with homologous target capability to tumor sites. The combinational approach exhibited favorable therapeutic efficacy against OS in vitro and in vivo. Impressively, the potential mechanisms are revealed by mRNA sequencing. This study provides a tactical design and typical paradigm of the synergized differentiation and ferroptosis therapies to combat heterogeneous OS.


Assuntos
Neoplasias Ósseas , Ferroptose , Osteossarcoma , Humanos , Adolescente , Espécies Reativas de Oxigênio , Apoptose , Osteossarcoma/tratamento farmacológico , Neoplasias Ósseas/tratamento farmacológico , Diferenciação Celular , Linhagem Celular Tumoral
18.
Phytomedicine ; 118: 154980, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37499344

RESUMO

BACKGROUND: Airway epithelial barrier dysfunction is highly related to the pathogenesis of chronic obstructive pulmonary disease (COPD). Effective-component combination (ECC) derived from Bufei Yishen formula (BYF) is an effective treatment regimen for patients with COPD and has previously been found to attenuate COPD and airway epithelial inflammation in rats. PURPOSE: To determine the mechanism underlying the protective effects of ECC-BYF against the disruption of the airway epithelial barrier in COPD. METHODS: The protective effects of ECC-BYF on the airway epithelial barrier were investigated in a rat COPD model. BEAS-2B epithelial cells were stimulated with cigarette smoke extract (CSE) to determine the direct effects of ECC-BYF on epithelial barrier function and aryl hydrocarbon receptor (AHR)/ epidermal growth factor receptor (EGFR) signaling. RESULTS: The results revealed that ECC-BYF attenuated COPD in rats and maintained the airway epithelial barrier by upregulating the expression of apical junction proteins, including occludin (OCC), zonula occludens (ZO)-1, and E-cadherin (E-cad). In BEAS-2B cells, ECC-BYF decreased permeability, increased transepithelial electrical resistance, and prevented the decrease in OCC, ZO-1, and E-cad expression induced by CSE exposure. In addition, transcriptomics and network analysis revealed that the protective effects of ECC-BYF may be related to multiple signaling pathways, including ErbB, AHR, and PI3K-Akt-mTOR pathways. ECC-BYF treatment suppressed the protein levels of p-EGFR and p-ERK1/2 and mRNA levels of CYP1A1 in CSE-exposed BEAS-2B cells as well as the protein levels of p-EGFR, p-ERK1/2, and CYP1A1 in the lungs of rats with COPD. In BEAS-2B cells, the AHR agonist FICZ weakened the protective effect of ECC-BYF on the epithelial barrier by suppressing the increase in ZO-1 and OCC expression induced by ECC-BYF and preventing the inhibitory effects of ECC-BYF on EGFR phosphorylation. CONCLUSIONS: This is the first study to demonstrate the protective effect of ECC-BYF on airway epithelial barrier function. The underlying mechanism may be associated with the suppression of the AHR/EGFR pathway to promote apical junction protein adhesion.


Assuntos
Doença Pulmonar Obstrutiva Crônica , Receptores de Hidrocarboneto Arílico , Ratos , Animais , Receptores de Hidrocarboneto Arílico/metabolismo , Citocromo P-450 CYP1A1/genética , Citocromo P-450 CYP1A1/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/metabolismo , Receptores ErbB/metabolismo , Células Epiteliais
19.
Bioconjug Chem ; 34(7): 1316-1326, 2023 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-37330989

RESUMO

Inflammation-related diseases affect large populations of people in the world and cause substantial healthcare burdens, which results in significant costs in time, material, and labor. Preventing or relieving uncontrolled inflammation is critical for the treatment of these diseases. Herein, we report a new strategy for alleviating inflammation by macrophage reprogramming via targeted reactive oxygen species (ROS) scavenging and cyclooxygenase-2 (COX-2) downregulation. As a proof of concept, we synthesize a multifunctional compound named MCI containing a mannose-based macrophage targeting moiety, an indomethacin (IMC)-based segment for inhibiting COX-2, and a caffeic acid (CAF)-based section for ROS clearance. As revealed by a series of in vitro experiments, MCI could significantly attenuate the expression of COX-2 and the level of ROS, leading to M1 to M2 macrophage reprogramming, as evidenced by the reduction and the elevation in the levels of pro-inflammatory M1 markers and anti-inflammatory M2 markers, respectively. Furthermore, in vivo experiments show MCI's promising therapeutic effects on rheumatoid arthritis (RA). Our work illustrates the success of targeted macrophage reprogramming for inflammation alleviation, which sheds light on the development of new anti-inflammatory drugs.


Assuntos
Inflamação , Macrófagos , Humanos , Ciclo-Oxigenase 2/metabolismo , Ciclo-Oxigenase 2/farmacologia , Ciclo-Oxigenase 2/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo , Regulação para Baixo , Inflamação/tratamento farmacológico , Inflamação/metabolismo
20.
Front Pharmacol ; 14: 1143768, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37251316

RESUMO

Quality marker (Q-marker) serves as an important driver for the standardization of quality control in traditional Chinese medicine (TCM) formulas. However, it is still challenging to discover comprehensive and representative Q-markers. This study aimed to identify Q-markers of Hugan tablet (HGT), a famous TCM formula with ideal clinical effects in liver diseases. Here, we proposed a funnel-type stepwise filtering strategy that integrated secondary metabolites characterization, characteristic chromatogram, quantitative analysis, literature mining, biotransformation rules and network analysis. Firstly, the strategy of "secondary metabolites-botanical drugs-TCM formula" was applied to comprehensively identify the secondary metabolites of HGT. Then, the secondary metabolites with specificity and measurability in each botanical drug were identified by HPLC characteristic chromatogram, biosynthesis pathway and quantitative analysis. Based on literature mining, the effectiveness of botanical metabolites that met the above conditions was evaluated. Furthermore, the metabolism of the above metabolites in vivo was studied to reveal their biotransformation forms, which were used for network analysis. At last, according to biotransformation rules of the prototype drugs in vivo, the secondary metabolites were traced and preliminarily chosen as Q-markers. As a result, 128 plant secondary metabolites were identified in HGT, and 11 specific plant secondary metabolites were screened out. Then, the content of specific plant secondary metabolites in 15 batches of HGT was determined, which confirmed their measurability. And the results of literature mining showed that eight secondary metabolites had therapeutic effects in treating liver disease at the in vivo level, and three secondary metabolites inhibited liver disease-related indicators at the in vitro level. After that, 26 compounds absorbed into the blood (11 specific plant metabolites and their 15 metabolites in vivo) were detected in rats. Moreover, 14 compounds, including prototype components and their metabolites, were selected as Q-marker candidates by the "TCM formula-botanical drugs-compounds-targets-pathways" network. Finally, 9 plant secondary metabolites were defined as comprehensive and representative Q-markers. Our study not only provides a scientific basis for the improvement and secondary development of the quality standard of HGT, but also proposes a reference method for discovering and identifying Q-markers of TCM preparations.

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