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1.
J Org Chem ; 89(7): 4619-4627, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38536672

RESUMO

Allyl sulfones are commonly present in bioactive compounds and organic building blocks. This work introduces a photocatalytic radical addition-elimination reaction involving readily accessible sulfonyl chlorides and allyl bromides. It delivers structurally diverse allylic sulfones in moderate to excellent yields, showcasing a high tolerance to functional groups. Notably, this method operates under mild reaction conditions without the need for oxidants, stoichiometric reducing metals, or additives.

2.
Molecules ; 28(12)2023 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-37375320

RESUMO

Twenty-four new phenylpropanoid esters of sucrose, phanerosides A-X (1-24), were isolated from an EtOH extract of the rattans of Phanera championii Benth. (Fabaceae). Their structures were elucidated on the basis of comprehensive spectroscopic data analysis. A wide range of structural analogues were presented due to the different numbers and positions of acetyl substituents and the structures of phenylpropanoid moieties. Phenylpropanoid esters of sucrose were isolated from the Fabaceae family for the first time. Biologically, the inhibitory effects of compounds 6 and 21 on NO production in LPS-induced BV-2 microglial cells were better than that of the positive control, with IC50 values of 6.7 and 5.2 µM, respectively. The antioxidant activity assay showed that compounds 5, 15, 17, and 24 displayed moderate DPPH radical scavenging activity, with IC50 values ranging from 34.9 to 43.9 µM.


Assuntos
Bauhinia , Sacarose , Sacarose/química , Ésteres/química , Antioxidantes/farmacologia , Antioxidantes/química , Estrutura Molecular
3.
Zhonghua Nan Ke Xue ; 29(10): 938-943, 2023 Oct.
Artigo em Zh | MEDLINE | ID: mdl-38639666

RESUMO

OBJECTIVE: To study the impact of the nursing model based on the interactive model of health behavior (IMCHB) on the self-efficacy and negative emotions of prostate cancer patients. METHODS: 70 cases clinically admitted to our hospital from January 1, 2021 to January 31, 2023 Patients who received radiotherapy for prostate cancer were taken as research subjects and divided into a control group (n=35) and an observation group (n=35) according to the random drawing method. The control group was given routine care, and the observation group was given a nursing model based on IMCHB on the basis of the control group. Compare the incidence of complications between the two groups, and use the Frankl Compliance Scale (FCS) to compare the compliance behaviors of the two groups, negative emotions on the day of admission and 1 day before discharge were statistically compared between the two groups Hamilton Depression Rating Scale (HAMD), Hamilton Anxiety Rating Scale (HAMA), and self-management efficacy General Self-Efficacy Scale (GSES)and quality of life World Health Organization Quality of Life Scale Short Form (WHOQOL-BREF). RESULTS: The incidence of radiation proctitis and radiation cystitis in observation group was lower than that in control group, the difference was statistically significant (P<0.05).The total compliance rate of medical compliance was 97.83%, which was higher than that of the control group, 84.78%, and the difference was statistically significant (P<0.05); 1 day before discharge, the HAMD and HAMA scores of the observation group were lower than those of the control group, GSES, and WHOQOL-BREF The score was higher than that of the control group, and the difference was statistically significant (P<0.05). CONCLUSION: The IMCHB nursing model can improve self-management efficiency and alleviate negative emotions when applied to patients undergoing radiotherapy for prostate cancer.


Assuntos
Neoplasias da Próstata , Qualidade de Vida , Masculino , Humanos , Autoeficácia , Comportamentos Relacionados com a Saúde , Modelos de Enfermagem , Neoplasias da Próstata/radioterapia , Emoções
4.
Oral Dis ; 2022 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-36076350

RESUMO

OBJECTIVE: Periodontitis is characterized by alveolar bone injury and absorption, with high incidence and poor treatment effect. Proliferation, migration, differentiation and apoptosis of osteoblasts are identified as key factors during the regeneration of alveolar bone tissue processes. Periodontal ligament stem cells (PDLSCs) have been proved to be a possible candidate for the treatment of periodontitis due to its multiple advantages, such as increasing the regenerative capacity of bone tissue. However, the effect of exosomes derived from PDLSCs (PDLSC-Exo) on osteoblasts remains to be further studied. METHODS AND MATERIALS: In this work, cell proliferation, migration, osteogenic differentiation, and H2 O2 -induced apoptosis were detected after cells were exposed to PDLSC-Exo by CCK-8, scratch wound assay, alizarin red S and alkaline phosphatase staining, real-time PCR, flow cytometry, tunel assay, and so on. Moreover, the activation of PI3K/AKT and MEK/ERK signaling pathways was evaluated by western blotting. RESULTS: We found that PDLSC-Exo are capable of promoting hFOB1.19 cell proliferation, migration and osteogenic differentiation, inhibiting H2 O2 -induced apoptosis, and activating the PI3K/AKT and MEK/ERK signaling pathways. CONCLUSION: These results suggest that PDLSC-Exo may be a promising therapeutic for osteoblastic damage.

5.
Bioorg Chem ; 116: 105332, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34509045

RESUMO

Sixteen chebulic acid derivatives, including nine new (1-9) and seven known (10-16) ones, were isolated from an ethanol extract of the branches and leaves of Balakata baccata. The structures of the new compounds were elucidated by their UV, IR, HRESIMS, NMR, electronic circular dichroism (ECD) and single-crystal X-ray diffraction data. The effects of all the isolates on antineuroinflammatory and antioxidant activities were evaluated. Compared with the positive control minocycline (IC50 = 1.21 ± 0.71 µM), compounds 1-16 with IC50 values being greater than 50 µM, displayed almost no effects on the inhibition of NO production in LPS-induced BV-2 microglial cells, however, the results of antioxidant activity for compounds 1-16 showed significant DPPH-radical scavenging abilities with EC50 value ranging from 3.98 to 14.24 µM, while the EC50 value of positive control vitamin C was 14.31 µM. At last, the results of PCR (qRT-PCR) analysis showed that compound 1 could enhance the expression of antioxidases (HO-1, GCLC, and NQO1) at the mRNA levels.


Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Benzopiranos/farmacologia , Inflamação/tratamento farmacológico , Sapium/química , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Antioxidantes/química , Antioxidantes/isolamento & purificação , Benzopiranos/química , Benzopiranos/isolamento & purificação , Compostos de Bifenilo/antagonistas & inibidores , Linhagem Celular , Relação Dose-Resposta a Droga , Inflamação/metabolismo , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Camundongos , Estrutura Molecular , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/biossíntese , Picratos/antagonistas & inibidores , Folhas de Planta/química , Relação Estrutura-Atividade
6.
Chem Soc Rev ; 48(12): 3229-3264, 2019 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-31119231

RESUMO

Supercapacitors hold great promise for future electronic systems that are moving towards being flexible, portable, and highly integrated, due to their superior power density, stability and cycle lives. Printed electronics represents a paradigm shift in the manufacturing of supercapacitors in that it provides a whole range of simple, low-cost, time-saving, versatile and environmentally-friendly manufacturing technologies for supercapacitors with new and desirable structures (micro-, asymmetric, flexible, etc.), thus unleashing the full potential of supercapacitors for future electronics. In this review, we start by introducing the structural features of printed supercapacitors, followed by a summary of materials related to printed supercapacitors, including electrodes, electrolytes, current collectors and substrates; then the approaches to improve the performance of printed supercapacitors by tuning printing processes are discussed; next a summary of the recent developments of printed supercapacitors is given in terms of specific printing methods utilized; finally, challenges and future research opportunities of this exciting research direction are presented.

7.
J Nanosci Nanotechnol ; 19(9): 5656-5660, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-30961721

RESUMO

Polypyrrole encapsulated nickel nanorods (PPy@Ni) have been prepared by electro-polymerization using Ni nanorods as template. PPy@Ni were characterized using transmission electron microscopy (TEM), scanning electron microscopy (SEM), X-ray diffraction (XRD), Raman spectrometer, Fourier transform infrared (FTIR) spectra and vibrating sample magnetometry (VSM). The maximum saturation magnetization of PPy@Ni was up to 44.6 emu g-1. Further, PPy@Ni was used as the additive for the conductivity improvement in polymer matrix. Experimental results showed that the electric conductivity reached 1.8×10-3 S m-1 when 5% PPy@Ni was added in the poly(urethane acrylate) matrix by applying a magnetic field. Further tests showed that when the additive concentration increased from 0.1% to 5%, the correspondence saturation magnetization increased from 15.1 emug-1 to 31.3 emug-1. This work provides new light on controllable fabrication of conducting polymer by adding magnetic alignment conductive additives.

8.
AJR Am J Roentgenol ; 209(3): 567-575, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28657846

RESUMO

OBJECTIVE: The purpose of this article is to review the mechanisms of action of immune checkpoint inhibitors in the treatment of non-small cell lung cancer (NSCLC), highlight imaging manifestations of common adverse events, and discuss new criteria for using imaging to assess unique treatment response patterns. CONCLUSION: Immune checkpoint inhibitor therapy is a breakthrough in cancer treatment that has shown unprecedented success when used for a variety of malignancies. In recent phase 3 clinical trials for NSCLC, monoclonal antibodies that target the programmed death-1 (PD-1) receptor and its ligand PD-L1 (i.e., the PD-1/PD-L1 axis) were associated with better overall survival in head-to-head comparisons with conventional cytotoxic chemotherapy. On the strength of the results of these trials, the PD-1 inhibitors nivolumab and pembrolizumab and the PD-L1 inhibitor atezolizumab recently received regulatory approval by the U.S. Food and Drug Administration for the treatment of advanced NSCLC. Because of their unique mechanisms of action, these agents differ from conventional cytotoxic chemotherapy in both patterns of treatment response and treatment-related adverse events. Given the rapidly expanding clinical use of immune checkpoint inhibitors and the central role of radiology in the care of patients with lung cancer, it is important for radiologists to be familiar with these agents and their unique imaging findings.


Assuntos
Anticorpos Monoclonais/farmacologia , Antineoplásicos/farmacologia , Imunoterapia/métodos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/imunologia , Anticorpos Monoclonais Humanizados , Humanos , Nivolumabe , Receptor de Morte Celular Programada 1/antagonistas & inibidores
9.
BMC Infect Dis ; 17(1): 366, 2017 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-28545411

RESUMO

BACKGROUND: Antimicrobial resistance (AMR) and genetic determinants of resistance of N. gonorrhoeae isolates from Hefei, China, were characterized adding a breadth of information to the molecular epidemiology of gonococcal resistance in China. METHODS: 126 N. gonorrhoeae isolates from a hospital clinic in Hefei, were collected between January, 2014, and November, 2015. The minimum inhibitory concentration (MIC) of N. gonorrhoeae isolates for seven antimicrobials were determined by the agar dilution method. Isolates were tested for mutations in penA and mtrR genes and 23S rRNA, and also genotyped using N. gonorrhoeae multi-antigen sequence typing (NG-MAST). RESULTS: All N. gonorrhoeae isolates were resistant to ciprofloxacin; 81.7% (103/126) to tetracycline and 73.8% (93/126) to penicillin. 39.7% (50/126) of isolates were penicillinase producing N. gonorrhoeae (PPNG), 31.7% (40/126) were tetracycline resistant N. gonorrhoeae (TRNG) and 28.6% (36/126) were resistant to azithromycin. While not fully resistant to extended spectrum cephalosporins (ESCs), a total of 14 isolates (11.1%) displayed decreased susceptibility to ceftriaxone (MIC ≥ 0.125 mg/L, n = 10), cefixime (MIC ≥ 0. 25 mg/L, n = 1) or to both ESCs (n = 3). penA mosaic alleles XXXV were found in all isolates that harbored decreased susceptibility to cefixime, except for one. Four mutations were found in mtrR genes and mutations A2143G and C2599T were identified in 23S rRNA. No isolates were resistant to spectinomycin. Gonococcal isolates were distributed into diverse NG-MAST sequence types (STs); 86 separate STs were identified. CONCLUSIONS: N. gonorrhoeae isolates from Hefei during 2014-2015, displayed high levels of resistance to antimicrobials that had been recommended previously for treatment of gonorrhea, e.g., penicillin, tetracycline and ciprofloxacin. The prevalence of resistance to azithromycin was also high (28.6%). No isolates were found to be fully resistant to spectinomycin, ceftriaxone or cefixime; however, 11.1% isolates, overall, had decreased susceptibility to ESCs.


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana/genética , Gonorreia/microbiologia , Neisseria gonorrhoeae/efeitos dos fármacos , Neisseria gonorrhoeae/genética , Azitromicina/farmacologia , Proteínas de Bactérias/genética , Cefalosporinas/farmacologia , China/epidemiologia , Ciprofloxacina/farmacologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Genótipo , Gonorreia/epidemiologia , Humanos , Testes de Sensibilidade Microbiana , Epidemiologia Molecular , Mutação , Neisseria gonorrhoeae/isolamento & purificação , Penicilinas/farmacologia , Proteínas Repressoras/genética , Espectinomicina/farmacologia , Tetraciclina/farmacologia , beta-Lactamases/genética
10.
Fitoterapia ; 172: 105740, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37939734

RESUMO

Three new phenolic glycosides (1-3) and a new lignan glycoside (4), together with five known compounds (5-9) were isolated from the ethanol extract of the aerial part of Gaultheria leucocarpa var. yunnanensis (Franch.) T.Z.Hsu & R.C.Fang. Their structures were determined on the basis of spectroscopic techniques, experimental and calculated ECD spectra, acid hydrolysis, and enzymatic hydrolysis experiments. All the isolates were evaluated for their anti-inflammatory and antioxidant activities. Compounds 7 and 8 exhibited inhibitory effects against the LPS-induced production of NO with IC50 of 63.71 and 10.66 µM, respectively, compared to L-NMMA having an IC50 of 6.95 µM. Besides, compound 7 also represented significant DPPH radical scavenging activity with EC50 of 18.75 µM, comparable with vitamin C (EC50 = 15.77 µM).


Assuntos
Glicosídeos Cardíacos , Gaultheria , Lignanas , Glicosídeos/química , Lignanas/farmacologia , Gaultheria/química , Estrutura Molecular , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química
11.
Phytomedicine ; 135: 156140, 2024 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-39405611

RESUMO

BACKGROUND: In the traditional "Yao" ethno-medicine system, Piper hancei Maxim. is used to treat rheumatism, wind-cold, and inflammation. Previous studies indicate that lignans obtained from P. hancei stems have anti-neuroinflammatory potential in LPS-stimulated microglial cells. However, identification of the lignan enantiomers and the precise mechanism by which they work to reduce inflammation is yet to be explored. PURPOSE: To identify the active anti-neuroinflammatory lignan enantiomers isolated from P. hancei stems and to elucidate the mechanism of action both in vitro and in vivo. METHODS: The lignan enantiomers from P. hancei stems were isolated and elucidated using various chromatographic and spectroscopic methods. The anti-neuroinflammatory potential of all the compounds was initially screened by measuring nitric oxide (NO) inhibition in LPS-stimulated BV-2 microglial cells. Then anti-neuroinflammatory efficacy of the most active compound was assessed with LPS-stimulated microglial cell model, microglia-induced neuronal injury SH-SY5Y cell model, and LPS-intracerebroventricular injection neuroinflammation mouse model. The underlying mechanism was further explored by qRT-PCR analysis, Western blot analysis, and immunofluorescence staining experiments to understand the intervention pathway. RESULTS: Phytochemical analysis of P. hancei stems resulted in the isolation of 13 pairs of neolignan enantiomers (1-13), including 4 new pairs named piperhancin D-G (1-4). All right-handed (+) and left-handed (-) enantiomers of each pair (1-13) were isolated successfully. Notably, (+)-futoquinol (5) demonstrated significant anti-neuroinflammatory activity without cytotoxicity, unlike its inactive enantiomer (-)-5 in LPS-stimulated microglial cells. The representative compound (+)-5 effectively suppressed pro-inflammatory cytokines in LPS stimulated BV-2 cells and mouse brains, and alleviated microglia-induced neuronal damage in SH-SY5Y cells. Behavioral tests showed that (+)-5 alleviated the LPS-induced cognitive dysfunction in mice. Furthermore, the compound was able to reduce LPS-induced neuronal damage and microglial activation in mouse brains. A mechanistic study demonstrated that (+)-5 hindered the nuclear translocation of NF-κB p65 and downregulated the pro-inflammatory mediators to relieve neuroinflammation. CONCLUSION: This is the first example of both in vitro and in vivo study on the anti-neuroinflammatory effects and underlying mechanism of the neolignan enantiomers isolated from P. hancei. Notably, (+)-futoquinol (5) emerged as a potential lead for further drug development to treat neurodegenerative diseases.

12.
Phytochemistry ; 219: 113973, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38211849

RESUMO

Nine undescribed sesquiterpene lactones, including two pseudoguaianolide dimers (1 and 2), a pseudoguaiac dilactone (3), and six pseudoguaianolides (4-9), along with 13 known analogues (10-22) were isolated from Parthenium hysterophorus. Among them, hysterolide A (1) possesses an unusual carbon skeleton with a unique cyclobutane ring connecting two pseudoguaianolides. Hysterolide C (3) is a sesquiterpene dilactone incorporating a bicyclo[5.1.0]octane core. Spectroscopic analyses, 13C NMR and ECD calculations, and X-ray diffraction elucidated their structures and absolute configurations. Moreover, all the isolates were assayed for their anti-inflammatory activities by inhibiting LPS-induced nitric oxide production in BV-2 microglia cells, wherein, nine compounds displayed significant inhibitory activities with IC50 of 0.52-6.32 µM. Furthermore, the preliminary structure-activity relationship was also established.


Assuntos
Asteraceae , Sesquiterpenos , Estrutura Molecular , Parthenium hysterophorus , Lactonas/farmacologia , Lactonas/química , Espectroscopia de Ressonância Magnética , Sesquiterpenos/farmacologia , Sesquiterpenos/química , Asteraceae/química
13.
Nat Prod Res ; 38(6): 947-955, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37144415

RESUMO

Seven new glycosides (1 - 7) with galloyl groups and two known kaempferol glycosides (8 and 9) were obtained from the overground parts of Balakata baccata. The structures of the new compounds were determined by comprehensive spectroscopic analyses. The rarely seen allene moiety in compounds 6 and 7 were described by detailed analysis of 1D and 2D NMR data. The antineuroinflammatory effect of all the isolates was assessed through inhibiting nitric oxide (NO) production in lipopolysaccharide (LPS)-induced BV-2 microglial cells. Compounds 1, 2, 6, and 7 showed potent inhibitory activities with IC50 values of 25.7, 17.2, 15.5 and 24.4 µM, respectively, compared with the positive control minocycline (IC50 = 16.1 µM).


Assuntos
Glicosídeos , Microglia , Sapium , Glicosídeos/farmacologia , Glicosídeos/química , Espectroscopia de Ressonância Magnética , Óxido Nítrico , Estrutura Molecular
14.
Phytomedicine ; 128: 155455, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38513376

RESUMO

BACKGROUND: Ischemic stroke (IS) is a serious cerebrovascular disease characterized by significantly elevated mortality and disability rates, and the treatments available for this disease are limited. Neuroinflammation and oxidative stress are deemed the major causes of cerebral ischemic injury. N-Cinnamoylpyrrole alkaloids form a small group of natural products from the genus Piper and have not been extensively analyzed pharmacologically. Thus, identifying the effect and mechanism of N-cinnamoylpyrrole-derived alkaloids on IS is worthwhile. PURPOSE: The present research aimed to explore the antineuroinflammatory and antioxidative stress effects of N-cinnamoylpyrrole-derived alkaloids isolated from the genus Piper and to explain the effects and mechanism on IS. METHODS: N-cinnamoylpyrrole-derived alkaloids were isolated from Piper boehmeriaefolium var. tonkinense and Piper sarmentosum and identified by various chromatographic methods. Lipopolysaccharide (LPS)-induced BV-2 microglia and a mouse model intracerebroventricularly injected with LPS were used to evaluate the antineuroinflammatory and antioxidative stress effects. Oxygen‒glucose deprivation/reperfusion (OGD/R) and transient middle cerebral artery occlusion (tMCAO) models were used to evaluate the effect of PB-1 on IS. To elucidate the fundamental mechanism, the functional target of PB-1 was identified by affinity-based protein profiling (ABPP) strategy and verified by cellular thermal shift assay (CETSA), drug affinity responsive target stability (DARTS), and circular dichroism (CD) analyses. The effect of PB-1 on the NF-κB and NRF2 signaling pathways was subsequently evaluated via western blotting and immunofluorescence staining. RESULTS: The results showed that N-cinnamoylpyrrole-derived alkaloids significantly affected neuroinflammation and oxidative stress. The representative compound, PB-1 not only inhibited neuroinflammation and oxidative stress induced by LPS or OGD/R insult, but also alleviated cerebral ischemic injury induced by tMCAO. Further molecular mechanism research found that PB-1 promoted antineuroinflammatory and antioxidative stress activities via the NF-κB and NRF2 signaling pathways by targeting eEF1A1. CONCLUSION: Our research initially unveiled that the therapeutic impact of PB-1 on cerebral ischemic injury might rely on its ability to target eEF1A1, leading to antineuroinflammatory and antioxidative stress effects. The novel discovery highlights eEF1A1 as a potential target for IS treatment and shows that PB-1, as a lead compound that targets eEF1A1, may be a promising therapeutic agent for IS.


Assuntos
Alcaloides , AVC Isquêmico , Piper , Pirróis , Animais , Masculino , Camundongos , Alcaloides/farmacologia , Alcaloides/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Antioxidantes/farmacologia , Antioxidantes/química , Modelos Animais de Doenças , AVC Isquêmico/tratamento farmacológico , Lipopolissacarídeos , Camundongos Endogâmicos C57BL , Microglia/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/química , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Piper/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Pirróis/farmacologia , Pirróis/química , Cinamatos/química , Cinamatos/farmacologia , Fator 1 de Elongação de Peptídeos/antagonistas & inibidores , Fator 1 de Elongação de Peptídeos/metabolismo
15.
Front Immunol ; 15: 1287132, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38348024

RESUMO

Background: Neutrophil extracellular traps (NETs) play a key role in thrombus formation in patients with coronavirus disease 2019 (COVID-19). However, the existing detection and observation methods for NETs are limited in their ability to provide quantitative, convenient, and accurate descriptions of in situ NETs. Therefore, establishing a quantitative description of the relationship between NETs and thrombosis remains a challenge. Objective: We employed morphological observations of blood cells and statistical analyses to investigate the correlation between the NETs/neutrophilic segmented granulocyte ratio and mortality risk in patients with COVID-19. Methods: Peripheral blood samples were collected from 117 hospitalized patients with COVID-19 between November 2022 and February 2023, and various blood cell parameters were measured. Two types of smudge cells were observed in the blood and counted: lymphatic and neutral smudge cells. Statistical data analysis was used to establish COVID-19 mortality risk assessment indicators. Results: Morphological observations of neutrophilic smudge cells revealed swelling, eruption, and NETs formation in the neutrophil nuclei. Subsequently, the NETs/neutrophilic segmented granulocyte ratio (NNSR) was calculated. A high concentration of NETs poses a fatal risk for thrombus formation in patients. Statistical analysis indicated that a high NNSR was more suitable for evaluating the risk of death in patients with COVID-19 compared to elevated fibrinogen (FIB) and D-dimer (DD) levels. Conclusion: Observing blood cell morphology is an effective method for the detection of NETs, NNSR are important markers for revealing the mortality risk of patients with COVID-19.


Assuntos
COVID-19 , Armadilhas Extracelulares , Trombose , Humanos , Armadilhas Extracelulares/metabolismo , COVID-19/metabolismo , Neutrófilos/metabolismo , Trombose/metabolismo
16.
J Mol Neurosci ; 74(2): 52, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38724832

RESUMO

Treatment of glioblastoma multiforme (GBM) remains challenging. Unraveling the orchestration of glutamine metabolism may provide a novel viewpoint on GBM therapy. The study presented a full and comprehensive comprehending of the glutamine metabolism atlas and heterogeneity in GBM for facilitating the development of a more effective therapeutic choice. Transcriptome data from large GBM cohorts were integrated in this study. A glutamine metabolism-based classification was established through consensus clustering approach, and a classifier by LASSO analysis was defined for differentiating the classification. Prognosis, signaling pathway activity, tumor microenvironment, and responses to immune checkpoint blockade (ICB) and small molecular drugs were characterized in each cluster. A combinational therapy of glutaminase inhibitor CB839 with dihydroartemisinin (DHA) was proposed, and the influence on glutamine metabolism, apoptosis, reactive oxygen species (ROS), and migration was measured in U251 and U373 cells. We discovered that GBM presented heterogeneous glutamine metabolism-based clusters, with unique survival outcomes, activity of signaling pathways, tumor microenvironment, and responses to ICB and small molecular compounds. In addition, the classifier could accurately differentiate the two clusters. Strikingly, the combinational therapy of CB839 with DHA synergistically attenuated glutamine metabolism, triggered apoptosis and ROS accumulation, and impaired migrative capacity in GBM cells, demonstrating the excellent preclinical efficacy. Altogether, our findings unveil the glutamine metabolism heterogeneity in GBM and propose an innovative combination therapy of CB839 with DHA for this malignant disease.


Assuntos
Artemisininas , Neoplasias Encefálicas , Glioblastoma , Glutamina , Glioblastoma/metabolismo , Glioblastoma/tratamento farmacológico , Humanos , Glutamina/metabolismo , Linhagem Celular Tumoral , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/tratamento farmacológico , Artemisininas/uso terapêutico , Artemisininas/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Glutaminase/metabolismo , Glutaminase/antagonistas & inibidores , Microambiente Tumoral , Apoptose , Tiadiazóis/farmacologia , Tiadiazóis/uso terapêutico , Movimento Celular , Benzenoacetamidas/farmacologia , Benzenoacetamidas/uso terapêutico , Antineoplásicos/uso terapêutico , Antineoplásicos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia
17.
Front Cell Dev Biol ; 11: 1225449, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37842095

RESUMO

Introduction: Curcumin has broad application prospects in the prevention and treatment of periodontal diseases. Periodontal ligament stem cell-derived extracellular vesicles (PDLSC-EV) can effectively promote periodontal tissue regeneration and possess good drug delivery capability. Superior pharmacological effects can be exerted using PDLSC-EV as a curcumin carrier. Methods: In the present study, we constructed curcumin-primed PDLSCs-derived extracellular vesicles (Cur-PDLSC-EV) from cell culture supernatants of curcumin-pretreated PDLSCs by ultracentrifugation and investigated their effects on the proliferation, migration, and osteogenic ability of PDLSCs and the corresponding downstream molecular pathways. Results: Both Cur-PDLSC-EV and PDLSC-EV promoted osteoblast proliferation and migration. Compared with PDLSC-EV, Cur-PDLSC-EV possessed a more potent pro-osteogenic ability. Moreover, the improved osteogenesis of Cur-PDLSC-EV was related to the activation of the Wnt/ß-catenin signaling pathway. Conclusion: This study suggests that Cur-PDLSC-EV can promote osteogenic differentiation by activating Wnt/ß-catenin, providing reference bases for the treatment of periodontal diseases.

18.
Expert Opin Drug Deliv ; 20(9): 1209-1229, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37776531

RESUMO

INTRODUCTION: Porous coordination networks (PCNs) have been widely used in large number of applications such as light harvesting, catalysis, and biomedical applications. Inserting porphyrins into PCNs scaffolds can alleviate the solubility and chemical stability problems associated with porphyrin ligands and add functionality to PCNs. The discovery that some PCNs materials have photosensitizer and acoustic sensitizer properties has attracted significant attention in the field of biomedicine, particularly in cancer therapy. This article describes the latest applications of the porphyrin ligand-based family of PCNs in cancer chemodynamic therapy (CDT), photodynamic therapy (PDT), sonodynamic therapy (SDT), photothermal therapy (PTT), and combination therapies and offers some observations and reflections on them. AREAS COVERED: This article discusses the use of the PCN family of MOFs in cancer treatment, specifically focusing on chemodynamic therapy, sonodynamic therapy, photodynamic therapy, photothermal therapy, and combination therapy. EXPERT OPINION: Although a large number of PCNs have been developed for use in novel cancer therapeutic approaches, further improvements are needed to advance the use of PCNs in the clinic. For example, the main mechanism of action of PCNs against cancer and the metabolic processes in organisms, and how to construct PCNs that maintain good stability in the complex environment of organisms.


Assuntos
Estruturas Metalorgânicas , Neoplasias , Fotoquimioterapia , Porfirinas , Humanos , Porfirinas/uso terapêutico , Porfirinas/química , Porfirinas/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Neoplasias/tratamento farmacológico
19.
Int J Biol Macromol ; 232: 123473, 2023 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-36731707

RESUMO

Uncontrolled hemorrhage is a main cause of pre-hospital death. Given the importance of hemostatic wound dressings in pre-hospital emergency treatment, novel composite materials are required for fast hemostasis, synergistic bacterial ablation with negligible resistance and wound healing acceleration. Herein, multifunctional SCTF cryogels were fabricated by the simultaneous cross-linking of sodium alginate (SA) and tannic acid (TA) with Fe3+ ions. As a result, the prepared SCTF cryogels consisted of Fe3+/TA-based metal phenolic networks (MPNs) and Fe3+/SA-based 3D skeleton for collagen (CA). MPNs endowed the cryogels with photothermal effect, photothermal-enhanced Fenton activity and pH/photothermal dual-responsive release property of TA and Fe2+, which were beneficial for the antibacterial capacity. Due to the intrinsic high porosity, in vitro and in vivo assays demonstrated that SCTF cryogels possessed good hemostatic capacity. Moreover, the synergistic photothermal therapy (PTT), chemodynamic therapy (CDT) and pH/photothermal responsive chemo-therapy dramatically enhanced the bactericidal efficacy of SCTF cryogels both in vitro and in vivo. Eventually, their outstanding healing-accelerating effects were confirmed via animal experiments, which were attributed to the presence of CA and TA. Therefore, the developed composite materials could offer new strategy on exploiting multifunctional wound dressing for clinical applications in the future.


Assuntos
Criogéis , Hemostáticos , Animais , Criogéis/farmacologia , Alginatos/farmacologia , Cicatrização , Colágeno , Metais , Antibacterianos/farmacologia
20.
Phytochemistry ; 211: 113683, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37105349

RESUMO

Twelve pairs of sesquineolignan enantiomers (1a/1b-6a/6b and 1c/1d-6c/6d), including twenty one undescribed and three known (2b, 3b, and 4b) sesquineolignans were isolated from an ethanol extract of the stems and leaves of Neoshirakia japonica (Euphorbiaceae). The successful separation of twelve pairs of enantiomers with mirror image-like electronic circular dichroism (ECD) curves and opposite specific rotation values, as one of the most important steps in compound isolation, was carried out by chiral HPLC columns. The absolute configurations of all undescribed sesquineolignans were elucidated by comprehensive analysis of their experimental ECD spectra. The effects of all the isolates on antineuroinflammatory and radical scavenging activity were evaluated. Compared with the positive control minocycline (IC50 = 1.2 µM), compounds 1a/1b/1c/1d-6a/6b/6c/6d with IC50 values being greater than 50 µM displayed almost no effect on the inhibition of NO production in LPS-induced BV-2 microglial cells. The results of DPPH-radical scavenging activity for them showed that compound 3c had moderate radical scavenging ability (EC50 = 48.47 µM), while the EC50 value of positive control vitamin C was 18.21 µM.


Assuntos
Euphorbiaceae , Folhas de Planta , Microglia , Estrutura Molecular
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