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1.
Int J Biol Macromol ; 270(Pt 1): 132148, 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38723800

RESUMEN

Herein, a straightforward protocol was developed for the one-pot synthesis of N-doped lignosulfonate-derived carbons (NLDCs) with a tunable porous structure using natural amino acids-templated self-assembly strategy. Specifically, histidine was employed as a template reagent, leading to the preparation of 10-NLDC-21 with remarkable characteristics, including the large specific surface area (SBET = 1844.5 m2/g), pore volume (Vmes = 1.22 cm3/g) and efficient adsorption for atrazine (ATZ) removal. The adsorption behavior of ATZ by NLDCs followed the Langmuir and pseudo-second-order models, suggesting a monolayer chemisorption nature of ATZ adsorption with the maximum adsorption capacity reached up to 265.77 mg/g. Furthermore, NLDCs exhibited excellent environmental adaptability and recycling performance. The robust affinity could be attributed to multi-interactions including pore filling, electrostatic attraction, hydrogen bonding and π-π stacking between the adsorbents and ATZ molecules. This approach offers a practical method for exploring innovative bio-carbon materials for sewage treatment.

2.
J Nanobiotechnology ; 22(1): 215, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38693585

RESUMEN

Stem cells (SCs) have been used therapeutically for decades, yet their applications are limited by factors such as the risk of immune rejection and potential tumorigenicity. Extracellular vesicles (EVs), a key paracrine component of stem cell potency, overcome the drawbacks of stem cell applications as a cell-free therapeutic agent and play an important role in treating various diseases. However, EVs derived from two-dimensional (2D) planar culture of SCs have low yield and face challenges in large-scale production, which hinders the clinical translation of EVs. Three-dimensional (3D) culture, given its ability to more realistically simulate the in vivo environment, can not only expand SCs in large quantities, but also improve the yield and activity of EVs, changing the content of EVs and improving their therapeutic effects. In this review, we briefly describe the advantages of EVs and EV-related clinical applications, provide an overview of 3D cell culture, and finally focus on specific applications and future perspectives of EVs derived from 3D culture of different SCs.


Asunto(s)
Técnicas de Cultivo Tridimensional de Células , Vesículas Extracelulares , Células Madre , Vesículas Extracelulares/metabolismo , Humanos , Células Madre/citología , Células Madre/metabolismo , Animales , Técnicas de Cultivo Tridimensional de Células/métodos , Técnicas de Cultivo de Célula/métodos
3.
Carbohydr Polym ; 337: 122139, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-38710550

RESUMEN

A novel RG-I pectin-like polysaccharide, YJ3A1, was purified from the flowers of Rosa chinensis and its structure and hepatoprotective effect in vivo and in vitro were investigated. The backbone of this polysaccharide is mainly composed of 1, 4-galactan, 1, 4-linked α-GalpA and 1, 2-linked α-Rhap disaccharide repeating unit attached by 1, 6-linked ß-Galp or 1, 5-linked α-Araf on C-4 of the Rhap. Interestingly, oral administration of YJ3A1 significantly ameliorates NASH-associated inflammation, oxidative stress and fibrosis and does not affect the liver morphology of normal mice at a dose of 50 mg/kg. The mechanism study suggests that the biological activity may associate to inactivating of high-mobility group box 1 protein (HMGB1)/TLR4/NF-κB and Akt signaling pathways by restraining the expression and release of HMGB1, thereby impeding the effect of NASH. The current findings outline a novel leading polysaccharide for new drug candidate development against NASH.


Asunto(s)
Proteína HMGB1 , FN-kappa B , Enfermedad del Hígado Graso no Alcohólico , Pectinas , Rosa , Transducción de Señal , Receptor Toll-Like 4 , Animales , Rosa/química , Receptor Toll-Like 4/metabolismo , Proteína HMGB1/metabolismo , FN-kappa B/metabolismo , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Enfermedad del Hígado Graso no Alcohólico/patología , Transducción de Señal/efectos de los fármacos , Ratones , Pectinas/farmacología , Pectinas/química , Pectinas/aislamiento & purificación , Masculino , Humanos , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Ratones Endogámicos C57BL , Polisacáridos/farmacología , Polisacáridos/química , Polisacáridos/aislamiento & purificación , Estrés Oxidativo/efectos de los fármacos
4.
J Surg Res ; 298: 63-70, 2024 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-38574463

RESUMEN

INTRODUCTION: Isolated partial anomalous pulmonary venous connection (PAPVC) is difficult to diagnose, and surgical indications remain controversial. We reviewed 10 y of isolated PAPVC cases. METHODS: The data of patients with isolated PAPVC admitted to the Anzhen Congenital Heart Disease Department from 2010 to 2019 were reviewed retrospectively. RESULTS: Thirty patients, aged between 4 mo and 32 y, were included in this study. Significant correlations were found between the right ventricle (RV), end-diastolic dimension Z-score (RVED-z) and age (r = 0.398, P = 0.03), and between estimated pulmonary pressure and age (r = 0.423, P = 0.02). However, no significant correlations were found between the RVED-z and the number of anomalous pulmonary veins (r = 0.347, P = 0.061), between estimated pulmonary pressure and the RVED-z (r = 0.218, P = 0.248), and between estimated pulmonary pressure and the number of anomalous veins (r = 0.225, P = 0.232). Transthoracic echocardiography (TTE) confirmed 90% of isolated PAPVC cases. Surgical repair was performed in 29 patients with RV enlargement, persistent low weight, pulmonary hypertension, or respiratory symptoms. Among the surgical patients, nine had elevated pulmonary pressure before surgery, which decreased postoperatively; no mortality or reintervention was observed. The mean duration of echocardiographic follow-up was 1.9 y. CONCLUSIONS: TTE is recommended for routine assessments, and further clarification can be obtained with computed tomography when TTE proves inconclusive for diagnosis. Transesophageal echocardiography and computed tomography are further recommended for adult patients if TTE fails to provide clear results. PAPVC should be considered as an underlying cause when unexplained RV enlargement is observed. Surgery is recommended for patients with RV enlargement, pulmonary hypertension, or respiratory symptoms.

5.
Clin Transl Sci ; 17(3): e13770, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-38501942

RESUMEN

Renal fibrosis is a typical pathological change from chronic kidney disease (CKD) to end-stage renal failure, which presents significant challenges in prevention and treatment. The progression of renal fibrosis is closely associated with the "gut-kidney axis," therefore, although clinical intervention to modulate the "gut-kidney axis" imbalance associated with renal fibrosis brings hope for its treatment. In this study, we first identified the close relationship between renal fibrosis development and the intestinal microenvironment through fecal microtransplantation and non-absorbable antibiotics experiments. Then, we analyzed the specific connection between the intestinal microenvironment and renal fibrosis using microbiomics and metabolomics, screening for the differential intestinal metabolite. Potential metabolite action targets were initially identified through network simulation of molecular docking and further verified by molecular biology experiment. We used flow cytometry, TUNEL apoptosis staining, immunohistochemistry, and Western blotting to assess renal injury and fibrosis extent, exploring the potential role of gut microbial metabolite in renal fibrosis development. We discovered that CKD-triggered alterations in the intestinal microenvironment exacerbate renal injury and fibrosis. When metabolomic analysis was combined with experiments in vivo, we found that the differential metabolite xylitol delays renal injury and fibrosis development. We further validated this hypothesis at the cellular level. Mechanically, bromodomain-containing protein 4 (BRD4) protein exhibits strong binding with xylitol, and xylitol alleviates renal fibrosis by inhibiting BRD4 and its downstream transforming growth factor-ß (TGF-ß) pathway. In summary, our findings suggest that the natural intestinal metabolite xylitol mitigates renal fibrosis by inhibiting the BRD4-regulated TGF-ß pathway.


Asunto(s)
Proteínas Nucleares , Insuficiencia Renal Crónica , Humanos , Xilitol , Simulación del Acoplamiento Molecular , Factores de Transcripción , Insuficiencia Renal Crónica/tratamiento farmacológico , Fibrosis , Factor de Crecimiento Transformador beta , Proteínas que Contienen Bromodominio , Proteínas de Ciclo Celular
6.
Heliyon ; 10(6): e27498, 2024 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-38509938

RESUMEN

Objectives: This study aimed to explore the relationship between red blood cell distribution width (RDW) and all-cause mortality in critically ill patients undergoing intra-aortic balloon pumping (IABP) in the intensive care unit (ICU). Methods: This study retrospectively analyzed data from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. The primary endpoint was the 30-day mortality rate, while the secondary endpoint was the in-hospital mortality rate. Restricted cubic splines were used to assess the dose-response relationship. The receiver operating characteristic (ROC) curve and Kaplan-Meier curve analysis were carried out to evaluate the predictive performance of RDW. Moreover, multiple logistic regression analyses and subgroup analyses were conducted to investigate the relationship between RDW and 30-day mortality. Finally, propensity score matching (PSM) was performed to adjust for the imbalance of covariates. Results: In total, 732 patients were finally identified from the MIMIC-IV database in this study. The RDW of patients in the non-survivor group was significantly higher compared with those in the survivor group (P < 0.01). Multiple logistic regression analyses corroborated RDW was an independent predictor of all-cause 30-day mortality in critically ill patients post-IABP. Meanwhile, ROC analysis identified an RDW cutoff of 14.2%. High RDW patients exhibited a 131% (OR = 2.31, 95% CI: 1.49-3.61) elevated risk of 30-day mortality after adjusting for confounders in multivariable logistic regression. After PSM, 412 patients were included in the matched cohort. In the original and matched cohorts, the high RDW group had higher 30-day and in-hospital mortality rates, as well as longer ICU stays. Lastly, the area under the ROC curve for 30-day mortality was 0.686, with an optimal cutoff point of 14.2 for RDW (sensitivity: 69.09 % and specificity: 63.32%). Conclusion: RDW could be a simple and valuable prognostic tool to predict mortality in critically ill patients after IABP.

8.
Heliyon ; 10(3): e25711, 2024 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-38371985

RESUMEN

Background: The potential effect of removing danger-associated molecular patterns (DAMPs) from gut lymph on reducing acute lung injury (ALI) induced by gut ischemia-reperfusion injury (GIRI) is uncertain. This study aimed to investigate whether gut lymph purification (GLP) could improve GIRI-induced acute lung injury in rats by clearing danger-associated molecular patterns. Materials and methods: Rats were divided into four groups: Sham, GIRI, GIRI + gut lymph drainage (GLD), and GIRI + GLP. After successful modeling, lung tissue samples were collected from rats for hematoxylin-eosin (HE) staining and detection of apoptotic indexes. We detected the DAMPs levels in blood and lymph samples. We observed the microstructure of AEC Ⅱ and measured the expression levels of apoptosis indexes. Results: The GIRI group showed destruction of alveolar structure, thickened alveolar walls, and inflammatory cell infiltration. This was accompanied by significantly increased levels of high mobility group protein-1 (HMGB-1) and Interleukin-6 (IL-6), while reduced levels of heat shock protein 70 (HSP 70) and Interleukin-10 (IL-10) in both lymph and serum. In contrast, the lung tissue damage in the GIRI + GLP group was significantly improved compared to the GIRI group. This was evidenced by a reduction in the expression levels of HMGB-1 and IL-6 in both lymph and serum and an increase in HSP 70 and IL-10 levels. Additionally, organelle structure of AEC II was significantly improved in the GIRI + GLP group compared to the GIRI group. Conclusions: GLP inhibits inflammation and cell apoptosis in GIRI-induced ALI by blocking the link between DAMPs and mononuclear phagocytes, reducing the severity of ALI.

9.
Med ; 5(1): 42-61.e23, 2024 Jan 12.
Artículo en Inglés | MEDLINE | ID: mdl-38181791

RESUMEN

BACKGROUND: Oral antiviral drugs with improved antiviral potency and safety are needed to address current challenges in clinical practice for treatment of COVID-19, including the risks of rebound, drug-drug interactions, and emerging resistance. METHODS: Olgotrelvir (STI-1558) is designed as a next-generation antiviral targeting the SARS-CoV-2 main protease (Mpro), an essential enzyme for SARS-CoV-2 replication, and human cathepsin L (CTSL), a key enzyme for SARS-CoV-2 entry into host cells. FINDINGS: Olgotrelvir is a highly bioavailable oral prodrug that is converted in plasma to its active form, AC1115. The dual mechanism of action of olgotrelvir and AC1115 was confirmed by enzyme activity inhibition assays and co-crystal structures of AC1115 with SARS-CoV-2 Mpro and human CTSL. AC1115 displayed antiviral activity by inhibiting replication of all tested SARS-CoV-2 variants in cell culture systems. Olgotrelvir also inhibited viral entry into cells using SARS-CoV-2 Spike-mediated pseudotypes by inhibition of host CTSL. In the K18-hACE2 transgenic mouse model of SARS-CoV-2-mediated disease, olgotrelvir significantly reduced the virus load in the lungs, prevented body weight loss, and reduced cytokine release and lung pathologies. Olgotrelvir demonstrated potent activity against the nirmatrelvir-resistant Mpro E166 mutants. Olgotrelvir showed enhanced oral bioavailability in animal models and in humans with significant plasma exposure without ritonavir. In phase I studies (ClinicalTrials.gov: NCT05364840 and NCT05523739), olgotrelvir demonstrated a favorable safety profile and antiviral activity. CONCLUSIONS: Olgotrelvir is an oral inhibitor targeting Mpro and CTSL with high antiviral activity and plasma exposure and is a standalone treatment candidate for COVID-19. FUNDING: Funded by Sorrento Therapeutics.


Asunto(s)
Tratamiento Farmacológico de COVID-19 , COVID-19 , Inhibidores de Proteasa de Coronavirus , SARS-CoV-2 , Animales , Humanos , Ratones , Antivirales/farmacología , Antivirales/uso terapéutico , Catepsina L/antagonistas & inhibidores , COVID-19/prevención & control , Modelos Animales de Enfermedad , Ratones Transgénicos , Inhibidores de Proteasa de Coronavirus/química , Inhibidores de Proteasa de Coronavirus/farmacología , Proteasas 3C de Coronavirus/antagonistas & inhibidores , Tratamiento Farmacológico de COVID-19/métodos
10.
Medicine (Baltimore) ; 103(1): e36844, 2024 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-38181229

RESUMEN

BACKGROUND: Traditional Chinese medicine (TCM) has been used in China for a long time and is gradually gaining more and more recognition worldwide. Gualou Guizhi Decoction (GGD) has long been used as a folk medicine for the treatment of rheumatic diseases, but its bioactive components and therapeutic mechanisms are still unclear. METHODS: An integrated approach using network pharmacology and molecular docking and using methotrexate as a positive control drug. RESULTS: We obtained 157 active ingredients of GGD, 7542 RA disease targets and 49 intersecting targets. GO and KEGG enrichment analysis revealed that their functions were mainly related to cytokine active metal ion binding, enzyme binding and DNA binding, and enriched in TNF signaling pathway, T cell receptor signaling pathway, Toll-like receptor signaling pathway, RA pathway and other signaling pathways that are closely related to RA. The molecular docking results show that the effector components of GGD bind better to the core targets of RA, and some are even better than methotrexate. CONCLUSION: The therapeutic effect of GGD for RA is achieved by affecting the core targets such as VEGFA, IL-1ß, IL6, CXCL8, CCL2, and JUN, which together interfere with the tumor necrosis factor signaling pathway and RA pathway to treat RA. The above study provides new ideas for further exploration of this classic formula in the future.


Asunto(s)
Artritis Reumatoide , Metotrexato , Humanos , Metotrexato/farmacología , Metotrexato/uso terapéutico , Simulación del Acoplamiento Molecular , Farmacología en Red , Artritis Reumatoide/tratamiento farmacológico
11.
Int J Biol Macromol ; 259(Pt 2): 129327, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38219939

RESUMEN

A series of novel waterborne lignin-based epoxy resin emulsions (WLEPs) were successfully synthesized, and then the WLEPs were cured with polyamide (PA) to give formaldehyde-free wood adhesives with high-performance. The chemical structures and properties of WLEP emulsions were determined. The effects of the emulsifiers on thermal and mechanical properties of the adhesives were investigated, and the potential application of WLEPs in the formulation of plywood were also evaluated. The results demonstrated that the WLEP dispersions presented excellent storage stability (>180 days) with their viscosities range from 110 mPa·s to 470 mPa·s and particle sizes in the range of 321-696 nm, which were beneficial for the fluidity and permeability of the wood adhesives. Furthermore, the thermal and mechanical properties of adhesives could be tuned effectively by controlling the length of PEG chains. The adhesive bearing PEG 6000 exhibited the highest tensile strength of 24.0 MPa and Young's modulus of 1439 MPa. Notably, the plywood prepared with the resulting adhesives displayed good bonding performance, especially water resistance, which were much higher than the national standard requirement for exterior-grade plywood type I. These results indicated that the WLEPs could be used as sustainable alternatives for traditional formaldehyde-based wood adhesives in practical applications.


Asunto(s)
Resinas Epoxi , Lignina , Lignina/química , Adhesivos/química , Madera/química , Resistencia a la Tracción
12.
ACS Omega ; 9(3): 3173-3183, 2024 Jan 23.
Artículo en Inglés | MEDLINE | ID: mdl-38284027

RESUMEN

Artificial intelligence technology will be increasingly applied in the oil and gas industry. The rapid development of artificial intelligence technology can solve problems such as high environmental sensitivity and complex production processes in the oil and gas industry. In recent years, emerging technologies represented by artificial intelligence have developed rapidly, assisting petroleum enterprises in digital transformation and intelligent upgrading. This article elaborates on the development trend of artificial intelligence technology. Based on the business scenarios and characteristics of the oil and gas industry, the application status of artificial intelligence technology in domestic and foreign petroleum technology service enterprises was summarized and analyzed. The application scenarios of artificial intelligence technology in the fields of dynamic analysis of oil and gas reservoirs, intelligent historical fitting, numerical simulation proxy models, and production plan optimization were analyzed with emphasis. Based on the problems and challenges faced in the development process of oil and gas reservoirs, it is proposed that petroleum enterprises should attach importance to the "three modernizations" innovation of data standardization, oil and gas field intelligence, and platform collaboration, in order to achieve more refined intelligent analysis and management of oil and gas reservoirs and quickly develop more targeted oil and gas reservoir development plans to assist in the intelligent transformation of oil and gas reservoir development. On this basis, prospects for future artificial intelligence technology are proposed, pointing out that the development of artificial intelligence technology will be faster and faster, and there will be higher demand for artificial intelligence technology in the construction of digital oil and gas fields in China in the future. The research results have important reference value for the development of the oil and gas industry.

13.
Int J Biol Macromol ; 260(Pt 2): 129677, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38266831

RESUMEN

In this study, a simple and eco-friendly method was used to treat alkaline lignin with an acidic deep eutectic solvent (DES) to obtain regenerated lignin for the efficient adsorption of pollutant dyes from aqueous environment. Based on the yield and adsorption capacity of the sorbent for these dyes, conditions such as the type and concentration of DES component, solid-to-liquid ratio, reaction time, and temperature were optimized. By characterizing and comparing alkali lignin with regenerated lignin, a series of reactions were demonstrated to occur during the DES treatment process. The performance and mechanism of methylene blue and rhodamine B adsorption on regenerated lignin were studied systematically, and the maximum adsorbed amounts were 348.29 and 551.05 mg/g at 323 K, respectively. This study provides a new strategy for the green preparation of functionalized lignin and its use in the water pollutant treatment.


Asunto(s)
Contaminantes Ambientales , Contaminantes Químicos del Agua , Lignina , Agua , Colorantes , Disolventes Eutécticos Profundos , Adsorción , Contaminantes Químicos del Agua/análisis , Solventes
14.
Carbohydr Polym ; 326: 121637, 2024 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-38142102

RESUMEN

Studies have shown that terrestrial acidic polysaccharides containing carboxyl groups and seaweed sulfated polysaccharides have strong potential in anti-liver fibrosis. However, there is no investigation on the anti-liver fibrosis of fructan, a ubiquitous natural polysaccharide. The present study aimed to understand the effect of fructan in ameliorating carbon tetrachloride (CCl4)-induced liver fibrosis in mice. Here, an inulin-like fructan ABWW from Achyranthes bidentata Bl. was characterized by fructose enzymatic hydrolysis, methylation analysis, ESI-MS, and NMR. It was composed of →2)-ß-d-Fruf-(1→ and →2)-ß-d-Fruf-(1, 6→, terminated with →1)-α-d-Glcp and →2)-ß-d-Fruf residues. The biological studies showed that ABWW could improve liver damage and liver fibrosis induced by CCl4in vivo and inhibit hepatic stellate cell (HSC) activation and migration in vitro. We further demonstrated that ABWW inhibited LX2 activation via suppressing the FAK/PI3K/AKT signaling pathway. Hence, ABWW might be a potential novel active compound for anti-fibrosis new drug development.


Asunto(s)
Inulina , Proteínas Proto-Oncogénicas c-akt , Ratones , Animales , Proteínas Proto-Oncogénicas c-akt/metabolismo , Inulina/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Células Estrelladas Hepáticas , Transducción de Señal , Cirrosis Hepática/inducido químicamente , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/metabolismo , Tetracloruro de Carbono , Hígado/metabolismo
15.
Mar Biotechnol (NY) ; 26(1): 37-49, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38117374

RESUMEN

Serine protease inhibitors (SPIs) are abundantly reported for its inhibition against specific proteases involved in the immune responses, but SPI data related to calcareous shells are scarce. Previously, our research group has reported the proteome analysis of non-nucleated pearl powder, and a candidate matrix protein containing two Kunitz domains in the acid soluble fraction caught our attention. In the present study, the full-length cDNA sequence of HcKuSPI was obtained from Hyriopsis cumingii. HcKuSPI was specifically expressed in the mantle, with hybridization signals mainly concentrated to dorsal epithelial cells at the mantle edge and weak signals at the mantle pallium, suggesting HcKuSPI was involved in shell formation. HcKuSPI expression in the mantle was upregulated after Aeromonas hydrophila and Staphylococcus aureus challenge to extrapallial fluids (EPFs). A glutathione S transferase (GST)-HcKuSPI recombinant protein showed strong inhibitory activity against the proteases, trypsin and chymotrypsin. Moreover, HcKuSPI expression in an experimental group was significantly higher when compared with a control group during pellicle growth and crystal deposition in shell regeneration processes, while the organic shell framework of newborn prisms and nacre tablets was completely destroyed after HcKuSPI RNA interference (RNAi). Therefore, HcKuSPI secreted by the mantle may effectively neutralize excess proteases and bacterial proteases in the EPF during bacterial infection and could prevent matrix protein extracellular degradation by suppressing protease proteolytic activity, thereby ensuring a smooth shell biomineralization. In addition, GST-HcKuSPI was also crucial for crystal morphology regulation. These results have important implications for our understanding of the potential roles of SPIs during shell biomineralization.


Asunto(s)
Inhibidores de Serina Proteinasa , Unionidae , Animales , Humanos , Recién Nacido , Inhibidores de Serina Proteinasa/genética , Inhibidores de Serina Proteinasa/metabolismo , Unionidae/genética , Unionidae/metabolismo , Inmunidad Innata/genética , Antibacterianos/metabolismo , Péptido Hidrolasas/metabolismo
16.
Zhongguo Zhong Yao Za Zhi ; 48(18): 4852-4863, 2023 Sep.
Artículo en Chino | MEDLINE | ID: mdl-37802827

RESUMEN

The material basis and mechanism of Chaenomelis Fructus in the treatment of rheumatoid arthritis(RA) were explored by network pharmacology, and the potential anti-RA targets of Chaenomelis Fructus were verified by molecular docking and animal experiments. The active components and targets of Chaenomelis Fructus were searched against the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform. GeneCards, DisGeNET, and OMIM were used to obtain RA-related targets. The common targets shared by Chaenomelis Fructus and RA were considered as the potential targets of Chaenomelis Fructus in the treatment of RA. Cytoscape 3.9.0 was employed to establish a "traditional Chinese medicine-active component-common target-disease" network. The protein-protein interaction(PPI) network was established by STRING, and the core genes were visualized by RStudio 4.1.0. DAVID was used for Gene Ontology(GO) annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment to predict and visualize the involved signaling pathways. Molecular docking was carried out with the active components screened out as ligands and RA core genes as the targets. Finally, the prediction results were verified by animal experiments. Four main active components of Chaenomelis Fructus were obtained, which corresponded to 137 targets. Chaenomelis Fructus and RA shared 37 common targets. GO annotation yielded 239 terms(P<0.05), and KEGG pathway enrichment analysis screened out 94 signaling pathways(P<0.05), mainly involving interleukin-17(IL-17), tumor necrosis factor, Toll-like receptor, and nuclear factor-kappa B(NF-κB) signaling pathways. Molecular docking results showed that the main active components of Chaenomelis Fructus bound well with the core targets of RA. The results of animal experiments proved that Chaenomelis Fructus can alleviate joint swelling in the mice with RA. The results of ELISA showed that Chaenomelis Fructus lowered the levels of interleukin-6(IL-6) and interleukin-1ß(IL-1ß). Western blot showed that Chaenomelis Fructus down-regulated the protein level of vascular endothelial growth factor A(VEGFA). Chaenomelis Fructus exerts anti-inflammatory effect and reduces pannus formation by regulating the core targets such as VEGFA, IL-1ß, and IL6 in the treatment of RA. The findings of this study provide new ideas for the future treatment of RA with Chaenomelis Fructus.


Asunto(s)
Artritis Reumatoide , Medicamentos Herbarios Chinos , Animales , Ratones , Farmacología en Red , Factor A de Crecimiento Endotelial Vascular , Simulación del Acoplamiento Molecular , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/genética , Factor de Necrosis Tumoral alfa , FN-kappa B , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Medicina Tradicional China
17.
Diagnostics (Basel) ; 13(19)2023 Oct 04.
Artículo en Inglés | MEDLINE | ID: mdl-37835869

RESUMEN

BACKGROUND: Correctly distinguishing mass-forming chronic pancreatitis (MFCP) from pancreatic cancer (PC) is of clinical significance to determine optimal therapy and improve the prognosis of patients. According to research, inflammation status in PC is different from that in MFCP. Mean platelet volume/platelet ratio (MPR) is a platelet-related inflammation index which has been proven to be valuable in the diagnosis and prognosis of various malignant cancers due to the change in mean platelet volume and platelet count under abnormal inflammatory conditions caused by tumors. Thus, we conducted this study to investigate the clinical value of MPR in distinguishing MFCP from PC. METHODS: We retrospectively analyzed the data of 422 patients who were suspected to have PC during imaging examination at our department from January 2012 to December 2021. Included patients were divided into the PC (n = 383) and MFCP groups (n = 39), according to their pathological diagnosis. Clinical data including MPR were compared within these two groups and the diagnostic value was explored using logistic regression. The ROC curve between MPR and PC occurrence was drawn and an optimal cut-off value was obtained. Propensity score matching was applied to match MFCP patients with PC patients according to their age and carbohydrate antigen 19-9 (CA19-9). Differences in MPR between groups were compared to verify our findings. RESULTS: The area under the ROC curve between MPR and PC occurrence was 0.728 (95%CI: 0.652-0.805) and the optimal cut-off value was 0.045 with a 69.2% sensitivity and 68.0% accuracy. For all the included patients, MPRs in the MFCP and PC groups were 0.04 (0.04, 0.06) and 0.06 (0.04, 0.07), respectively (p = 0.005). In patients with matching propensity scores, MPRs in the MFCP and PC groups were 0.04 (0.03, 0.06) and 0.06 (0.05, 0.08), respectively (p = 0.005). Multiple logistic regression in all included patients and matched patients confirmed MPR and CA19-9 as independent risk markers in distinguishing PC. Combining CA19-9 with MPR can increase the sensitivity and accuracy in diagnosing PC to 93.2% and 89.5%, respectively. CONCLUSION: MPR in PC patients is significantly higher than that in MFCP patients and may be adopted as a potential indicator to distinguish MFCP and PC. Its differential diagnosis capacity can be improved if combined with CA19-9.

19.
Molecules ; 28(17)2023 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-37687147

RESUMEN

Crystallization selectivity is an important principle in polymorph control. Ribavirin Form I, Form II, DMSO solvate, and amorphous ribavirin are prepared, and the short-range order similarities between these solid forms and ribavirin aqueous solution and DMSO solution are compared via mid-frequency Raman difference spectra (MFRDS). The crystallization process from amorphous ribavirin to Form I and from solution to amorphous phase is explained. Reasons for the difficulty in preparing the DMSO solvate are proposed. The rationale provided for the crystallization selectivity provides a foundation for the synthesis of metastable phases with a robust and convenient method.

20.
Org Lett ; 25(36): 6773-6778, 2023 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-37655856

RESUMEN

A visible-light-driven desaturative ß-alkoxyoxalyation of N-aryl cyclic amines with difluoromethyl bromides and H2O has been reported. This tandem reaction is triggered by homolysis of the C-Br bond to produce the difuoroalkyl radical, which undergoes the subsequent defluorinated ß-alkoxyoxalylation cascades to afford a wide range of ß-ketoester/ketoamides substituted enamines. The prominent feature of this reaction contains photocatalyst-free, transition-metal free, and mild conditions. The 18O labeling experiment disclosed that H2O is the oxygen source of the carbonyl unit.

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