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1.
Biopharm Drug Dispos ; 45(3): 149-158, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38886878

RESUMO

Icaritin is a prenylflavonoid derivative of the genus Epimedium (Berberidaceae) and has a variety of pharmacological actions. Icaritin is approved by the National Medical Products Administration as an anticancer drug that exhibits efficacy and safety advantages in patients with hepatocellular carcinoma cells. This study aimed to evaluate the inhibitory effects of icaritin on UDP-glucuronosyltransferase (UGT) isoforms. 4-Methylumbelliferone (4-MU) was employed as a probe drug for all the tested UGT isoforms using in vitro human liver microsomes (HLM). The inhibition potentials of UGT1A1 and 1A9 in HLM were further tested by employing 17ß-estradiol (E2) and propofol (PRO) as probe substrates, respectively. The results showed that icaritin inhibits UGT1A1, 1A3, 1A4, 1A7, 1A8, 1A10, 2B7, and 2B15. Furthermore, icaritin exhibited a mixed inhibition of UGT1A1, 1A3, and 1A9, and the inhibition kinetic parameters (Ki) were calculated to be 3.538, 2.117, and 0.306 (µM), respectively. The inhibition of human liver microsomal UGT1A1 and 1A9 both followed mixed mechanism, with Ki values of 2.694 and 1.431 (µM). This study provides supporting information for understanding the drug-drug interaction (DDI) potential of the flavonoid icaritin and other UGT-metabolized drugs in clinical settings. In addition, the findings provide safety evidence for DDI when liver cancer patients receive a combination therapy including icaritin.


Assuntos
Interações Medicamentosas , Flavonoides , Glucuronosiltransferase , Microssomos Hepáticos , Glucuronosiltransferase/antagonistas & inibidores , Glucuronosiltransferase/metabolismo , Humanos , Flavonoides/farmacologia , Microssomos Hepáticos/metabolismo , Estradiol/farmacologia , Himecromona/farmacologia , Propofol/farmacologia , Inibidores Enzimáticos/farmacologia
2.
Int J Mol Sci ; 25(2)2024 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-38255822

RESUMO

Sepsis ranks among the most common health problems worldwide, characterized by organ dysfunction resulting from infection. Excessive inflammatory responses, cytokine storms, and immune-induced microthrombosis are pivotal factors influencing the progression of sepsis. Our objective was to identify novel immune-related hub genes for sepsis through bioinformatic analysis, subsequently validating their specificity and potential as diagnostic and prognostic biomarkers in an animal experiment involving a sepsis mice model. Gene expression profiles of healthy controls and patients with sepsis were obtained from the Gene Expression Omnibus (GEO) and analysis of differentially expressed genes (DEGs) was conducted. Subsequently, weighted gene co-expression network analysis (WGCNA) was used to analyze genes within crucial modules. The functional annotated DEGs which related to the immune signal pathways were used for constructing protein-protein interaction (PPI) analysis. Following this, two hub genes, FERMT3 and CD3G, were identified through correlation analyses associated with sequential organ failure assessment (SOFA) scores. These two hub genes were associated with cell adhesion, migration, thrombosis, and T-cell activation. Furthermore, immune infiltration analysis was conducted to investigate the inflammation microenvironment influenced by the hub genes. The efficacy and specificity of the two hub genes were validated through a mice sepsis model study. Concurrently, we observed a significant negative correlation between the expression of CD3G and IL-1ß and GRO/KC. These findings suggest that these two genes probably play important roles in the pathogenesis and progression of sepsis, presenting the potential to serve as more stable biomarkers for sepsis diagnosis and prognosis, deserving further study.


Assuntos
Experimentação Animal , Sepse , Animais , Humanos , Camundongos , Biomarcadores , Adesão Celular , Biologia Computacional , Modelos Animais de Doenças , Sepse/genética
3.
Molecules ; 29(2)2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38276624

RESUMO

LR004 is a novel chimeric (human/mouse) monoclonal antibody developed for the treatment of advanced colorectal carcinoma with detectable epidermal growth factor receptor (EGFR) expression. We aimed to investigate the preclinical pharmacokinetics (PK) and in vivo biodistribution of LR004. The PK profiles of LR004 were initially established in rhesus monkeys. Subsequently, 125I radionuclide-labeled LR004 was developed and the biodistribution, autoradiography, and NanoSPECT/CT of 125I-LR004 in xenograft mice bearing A431 tumors were examined. The PK data revealed a prolonged half-life and nonlinear PK characteristics of LR004 within the dose range of 6-54 mg/kg. The radiochemical purity of 125I-LR004 was approximately 98.54%, and iodination of LR004 did not affect its specific binding activity to the EGFR antigen. In a classical biodistribution study, 125I-LR004 exhibited higher uptake in highly perfused organs than in poorly perfused organs. Prolonged retention properties of 125I-LR004 in tumors were observed at 4 and 10 days. Autoradiography and NanoSPECT/CT confirmed the sustained retention of 125I-LR004 at the tumor site in xenograft mice. These findings demonstrated the adequate tumor targeting capabilities of 125I-LR004 in EGFR-positive tumors, which may improve dosing strategies and future drug development.


Assuntos
Antineoplásicos , Neoplasias Colorretais , Humanos , Animais , Camundongos , Distribuição Tecidual , Anticorpos Monoclonais , Receptores ErbB/metabolismo , Neoplasias Colorretais/tratamento farmacológico , Linhagem Celular Tumoral
4.
Cell Commun Signal ; 21(1): 34, 2023 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-36782203

RESUMO

Health hazards from long-term exposure to microwaves, especially the potential for changes in cognitive function, are attracting increasing attention. The purpose of this study was to explore changes in spatial learning and memory and synaptic structure and to identify differentially expressed proteins in hippocampal and serum exosomes after long-term exposure to 2.856 and 9.375 GHz microwaves. The spatial reference learning and memory abilities and the structure of the DG area were impaired after long-term exposure to 2.856 and 9.375 GHz microwaves. We also found a decrease in SNARE-associated protein Snapin and an increase in charged multivesicular body protein 3 in the hippocampus, indicating that synaptic vesicle recycling was inhibited and consistent with the large increase in presynaptic vesicles. Moreover, we investigated changes in serum exosomes after 2.856 and 9.375 GHz microwave exposure. The results showed that long-term 2.856 GHz microwave exposure could induce a decrease in calcineurin subunit B type 1 and cytochrome b-245 heavy chain in serum exosomes. While the 9.375 GHz long-term microwave exposure induced a decrease in proteins (synaptophysin-like 1, ankyrin repeat and rabankyrin-5, protein phosphatase 3 catalytic subunit alpha and sodium-dependent phosphate transporter 1) in serum exosomes. In summary, long-term microwave exposure could lead to different degrees of spatial learning and memory impairment, EEG disturbance, structural damage to the hippocampus, and differential expression of hippocampal tissue and serum exosomes.


Assuntos
Cognição , Micro-Ondas , Cognição/efeitos da radiação , Hipocampo/metabolismo , Hipocampo/efeitos da radiação , Micro-Ondas/efeitos adversos , Animais
5.
Molecules ; 28(16)2023 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-37630371

RESUMO

Astragaloside IV (AS-IV) is one of the main active components extracted from the Chinese medicinal herb Astragali and serves as a marker for assessing the herb's quality. AS-IV is a tetracyclic triterpenoid saponin in the form of lanolin ester alcohol and exhibits various biological activities. This review article summarizes the chemical structure of AS-IV, its pharmacological effects, mechanism of action, applications, future prospects, potential weaknesses, and other unexplored biological activities, aiming at an overall analysis. Papers were retrieved from online electronic databases, such as PubMed, Web of Science, and CNKI, and data from studies conducted over the last 10 years on the pharmacological effects of AS-IV as well as its impact were collated. This review focuses on the pharmacological action of AS-IV, such as its anti-inflammatory effect, including suppressing inflammatory factors, increasing T and B lymphocyte proliferation, and inhibiting neutrophil adhesion-associated molecules; antioxidative stress, including scavenging reactive oxygen species, cellular scorching, and regulating mitochondrial gene mutations; neuroprotective effects, antifibrotic effects, and antitumor effects.


Assuntos
Astrágalo , Saponinas , Triterpenos , Saponinas/farmacologia , Triterpenos/farmacologia , Proliferação de Células
6.
Molecules ; 28(21)2023 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-37959868

RESUMO

Radiation-induced skin injury (RISI) is a frequent and severe complication with a complex pathogenesis that often occurs during radiation therapy, nuclear incidents, and nuclear war, for which there is no effective treatment. Hyaluronan (HA) plays an overwhelming role in the skin, and it has been shown that UVB irradiation induces increased HA expression. Nevertheless, to the best of our knowledge, there has been no study regarding the biological correlation between RISI and HA degradation and its underlying mechanisms. Therefore, in our study, we investigated low-molecular-weight HA content using an enzyme-linked immunosorbent assay and changes in the expression of HA-related metabolic enzymes using real-time quantitative polymerase chain reaction and a Western blotting assay. The oxidative stress level of the RISI model was assessed using sodium dismutase, malondialdehyde, and reactive oxygen species assays. We demonstrated that low-molecular-weight HA content was significantly upregulated in skin tissues during the late phase of irradiation exposure in the RISI model and that HA-related metabolic enzymes, oxidative stress levels, the MEK5/ERK5 pathway, and inflammatory factors were consistent with changes in low-molecular-weight HA content. These findings prove that HA degradation is biologically relevant to RISI development and that the HA degradation mechanisms are related to HA-related metabolic enzymes, oxidative stress, and inflammatory factors. The MEK5/ERK5 pathway represents a potential mechanism of HA degradation. In conclusion, we aimed to investigate changes in HA content and preliminarily investigate the HA degradation mechanism in a RISI model under γ-ray irradiation, to consider HA as a new target for RISI and provide ideas for novel drug development.


Assuntos
Ácido Hialurônico , Pele , Ácido Hialurônico/farmacologia , Pele/metabolismo , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo , Oxirredução
7.
Ecotoxicol Environ Saf ; 243: 113983, 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-35985199

RESUMO

This study aimed to elucidate the effects and biological targets sensitive to simultaneous 1.5 and 4.3 GHz microwave exposure in rats. A total of 120 male Wistar rats were divided randomly into four groups: the sham (S group), 1.5 GHz microwave exposure (L group), 4.3 GHz microwave exposure (C group) and simultaneous 1.5 and 4.3 GHz microwave exposure (LC group) groups. Spatial learning and memory, cortical electrical activity, and hippocampal ultrastructure were assessed by the Morris Water Maze, electroencephalography, and transmission electron microscopy, respectively. Additionally, serum exosomes were isolated by ultracentrifugation and assessed by Western blotting, nanoparticle tracking and transmission electron microscopy. The serum exosome protein content was assessed by label-free quantitative proteomics. Impaired spatial learning and memory decreased cortical excitability, and damage to the hippocampal ultrastructure were observed in groups exposed to microwaves, especially the L and LC groups. A total of 54, 145 and 296 exosomal proteins were differentially expressed between the S group and the L, C and LC groups, respectively. These differentially expressed proteins were involved in the synaptic vesicle cycle and SNARE interactions during vesicular transport. Additionally, VAMP8, Syn7 and VMAT are potential serum markers of simultaneous microwave exposure. Thus, exposure to 1.5 and 4.3 GHz microwaves induced impairments in spatial learning and memory, and simultaneous microwave exposure had the most severe effects.


Assuntos
Exossomos , Micro-Ondas , Animais , Proteínas Sanguíneas/metabolismo , Hipocampo , Masculino , Aprendizagem em Labirinto , Micro-Ondas/efeitos adversos , Ratos , Ratos Wistar , Aprendizagem Espacial
8.
Endocr Res ; 47(1): 32-38, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34409914

RESUMO

PURPOSE: The purpose of this study is to review observational studies on the effect of insulin use and mortality in patients with COVID-19 and diabetes. METHODS: A systematic literature search was performed using the PubMed, Medline, EMBASE, and Cochrane Library databases. The meta-analysis was performed using a random effects model, and I2 was applied to evaluate heterogeneity. Sensitivity and subgroup analyses were also performed. RESULTS: Overall, 1,338 patients over six studies were ultimately included. Insulin use was related to a higher risk of death in diabetic patients with COVID-19 compared to those who did not use insulin (odds ratio: 2.59, 95% confidence interval: 1.66-4.05; P < .0001; I2: 57%). CONCLUSIONS: This meta-analysis revealed a correlation between insulin usage and increased mortality in diabetic patients with COVID-19. These results showed that insulin requirement in patients with COVID-19 and diabetes might indicate a poor prognosis.


Assuntos
COVID-19 , Diabetes Mellitus , Diabetes Mellitus/tratamento farmacológico , Humanos , Insulina , Estudos Observacionais como Assunto , SARS-CoV-2
9.
Molecules ; 27(7)2022 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-35408630

RESUMO

Significant efforts have been made in recent years to identify more environmentally benign and safe alternatives to side-chain protection and deprotection in solid-phase peptide synthesis (SPPS). Several protecting groups have been endorsed as suitable candidates, but finding a greener protecting group in SPPS has been challenging. Here, based on the 2-(o-nitrophenyl) propan-1-ol (Npp-OH) photolabile protecting group, a structural modification was carried out to synthesize a series of derivatives. Through experimental verification, we found that 3-(o-Nitrophenyl) butan-2-ol (Npb-OH) had a high photo-release rate, high tolerance to the key conditions of Fmoc-SPPS (20% piperidine DMF alkaline solution, and pure TFA acidic solution), and applicability as a carboxyl-protective group in aliphatic and aromatic carboxyl groups. Finally, Npb-OH was successfully applied to the synthesis of head-tail cyclic peptides and side-chain-tail cyclic peptides. Moreover, we found that Npb-OH could effectively resist diketopiperazines (DKP). The α-H of Npb-OH was found to be necessary for its photosensitivity in comparison to 3-(o-Nitrophenyl)but-3-en-2-ol (Npbe-OH) during photolysis-rate verification.


Assuntos
Peptídeos Cíclicos , Técnicas de Síntese em Fase Sólida , Fotólise
10.
Zhongguo Zhong Yao Za Zhi ; 46(17): 4334-4343, 2021 Sep.
Artigo em Zh | MEDLINE | ID: mdl-34581036

RESUMO

Xanthoceras sorbifolia, an excellent oil-rich woody species, has high comprehensive economic value in edible, medicinal, and ornamental fields. The chemical composition, pharmacological effect, and quality control of X. sorbifolia were introduced, and its development and application were reviewed in this study. As revealed by the previous research, the main chemical constituents of X. sorbifolia were triterpenoids, flavonoids, fatty acids, phenylpropanoids, steroids, phenolic acids, organic acids, etc. It possesses pharmacological effects, such as neuroprotection, bacteriostasis, anti-oxidation, anti-tumor, anti-inflammation, analgesia, anti-HIV, and anti-coagulation. X. sorbifolia is widely applied in medical, food, chemical industry, and other fields, and deserves in-depth research and development.


Assuntos
Sapindaceae , Triterpenos , Anti-Inflamatórios , Flavonoides , Pesquisa
11.
Chem Pharm Bull (Tokyo) ; 68(5): 443-446, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32173668

RESUMO

Coumarin moiety has garnered momentous attention especially in the design of compounds with significant biological activities. In this work, a series of 3-substituted coumarin derivatives 6a-6l were synthesized and fully characterized. Most of the compounds could obviously inhibit the activity of cyclooxygenase-1 (COX-1) at the concentration of 10 µM. Besides, 6h and 6l exhibited highest inhibitory effects against COX-2 with inhibition rates of 33.48 and 35.71%, respectively. Detailed structure-activity relationships (SARs) were also discussed. In vivo studies, 6b, 6i and 6l could remarkably repress the xylene-induced ear swelling in mice at the dose of 20 mg/kg. Especially, 6l seemed to be the most effective compound at the dose of 10 mg/kg, displaying favorable anti-inflammatory activity comparable to indomethacin. All of these findings suggested that 6l might be utilized as a candidate for the treatment of inflammatory diseases.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Cumarínicos/farmacologia , Inibidores de Ciclo-Oxigenase/farmacologia , Desenho de Fármacos , Otopatias/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Animais , Anti-Inflamatórios não Esteroides/síntese química , Anti-Inflamatórios não Esteroides/química , Sobrevivência Celular/efeitos dos fármacos , Cumarínicos/síntese química , Cumarínicos/química , Ciclo-Oxigenase 1/metabolismo , Ciclo-Oxigenase 2/metabolismo , Inibidores de Ciclo-Oxigenase/síntese química , Inibidores de Ciclo-Oxigenase/química , Relação Dose-Resposta a Droga , Otopatias/induzido quimicamente , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Camundongos , Estrutura Molecular , Células RAW 264.7 , Relação Estrutura-Atividade , Fator de Necrose Tumoral alfa/biossíntese , Xilenos
12.
Molecules ; 24(22)2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31703373

RESUMO

In this work, a series of benzylsulfone coumarin derivatives 5a-5o were synthesized and characterized. Kinase inhibitory activity assay indicated that most of the compounds showed considerable activity against PI3K. Anti-tumor activity studies of the active compounds were also carried out in vitro on the Hela, HepG2, H1299, HCT-116, and MCF-7 tumor cell lines by MTS assay. The structure-activity relationships (SARs) of these compounds were analyzed in detail. Compound 5h exhibited the most potent activities against the mentioned cell lines with IC50 values ranging from 18.12 to 32.60 µM, followed by 5m with IC50 values of 29.30-42.14 µM. Furthermore, 5h and 5m clearly retarded the migration of Hela cells in vitro. Next, an in silico molecular docking study was conducted to evaluate the binding models of 5h and 5m towards PI3Kα and PI3Kß. Collectively, the above findings suggested that compounds 5h and 5m might be promising PI3K inhibitors deserving further investigation for cancer treatment.


Assuntos
Antineoplásicos , Classe I de Fosfatidilinositol 3-Quinases/antagonistas & inibidores , Cumarínicos , Desenho de Fármacos , Inibidores Enzimáticos , Simulação de Acoplamento Molecular , Proteínas de Neoplasias/antagonistas & inibidores , Neoplasias/tratamento farmacológico , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Classe I de Fosfatidilinositol 3-Quinases/metabolismo , Cumarínicos/síntese química , Cumarínicos/química , Cumarínicos/farmacologia , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Células HCT116 , Células HeLa , Células Hep G2 , Humanos , Células MCF-7 , Proteínas de Neoplasias/metabolismo , Neoplasias/enzimologia
13.
BMC Anesthesiol ; 18(1): 168, 2018 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-30424730

RESUMO

BACKGROUND: Fluid overloading is detrimental to organ function and results in a poor prognosis. It is necessary to evaluate fluid responsiveness before fluid loading. We performed a systematic meta-analysis to evaluate the diagnostic value of the respiratory variation in peripheral arterial blood flow peak velocity (△Vpeak PA) in predicting fluid responsiveness in mechanically ventilated patients. METHODS: PubMed, Embase and The Cochrane Library databases were searched for studies that used △Vpeak PA to predict fluid responsiveness in mechanically ventilated patients. We calculated the pooled values of sensitivity, specificity and the area of the summary receiver operating characteristic curve by Meta-Disc 14.0 software. RESULTS: Nine studies with a total of 402 patients were included. Two low quality studies were deleted in further analysis. Moreover, because of different locations of peripheral artery, the rest included studies were divided into brachial site group and carotid site group for meta-analysis individually. The pooled sensitivity, specificity and area under curve were 0.85 (95% confidence interval (CI) 0.77-0.92), 0.86 (95% CI 0.77-0.92) and 0.9268 in carotid site group. The pooled sensitivity, specificity and area under curve were 0.72 (95% CI 0.60-0.81), 0.85 (95% CI 0.74-0.93) and 0.8587 in brachial site group. CONCLUSIONS: △Vpeak of carotid and brachial artery had a diagnostic value in predicting fluid responsiveness respectively. Moreover, △Vpeak of carotid artery had more value than brachial artery in predicting fluid responsiveness. However, there was some clinical heterogeneity; therefore, further studies are needed to confirm diagnostic accuracy.


Assuntos
Velocidade do Fluxo Sanguíneo/fisiologia , Cateterismo Periférico/tendências , Hidratação/tendências , Respiração Artificial/tendências , Mecânica Respiratória/fisiologia , Cateterismo Periférico/métodos , Hidratação/efeitos adversos , Previsões , Humanos , Respiração Artificial/métodos , Resultado do Tratamento , Ventiladores Mecânicos/tendências
14.
Kidney Blood Press Res ; 42(6): 1023-1032, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29212080

RESUMO

BACKGROUND/AIMS: This study aimed to report the clinical efficacy of continuous renal replacement therapy (CRRT) in combination with ultrasound-guided percutaneous transhepatic gallbladder drainage (PTGD) (CRRT+PTGD) in the treatment of acute severe biliary pancreatitis (ASBP). METHODS: Between January 2010 and January 2016, 40 cases of patients with ASBP who received routine CRRT (CRRT group) and 40 of those who received CRRT+PTGD (CRRT+PTGD group) at the Affiliated Hospital of Qingdao University (Qingdao, China) were retrospectively reviewed. Clinical (including abdominal pain remission time, gastrointestinal decompression time, Intensive Care Unit (ICU) hospital stay, respirator treatment time, and mortality rate), laboratory (white blood cells [WBC], platelet [PLT], procalcitonin [PCT], C-reactive protein [CRP], total bilirubin [TBIL], alanine aminotransferase [ALT], albumin [ALB], and blood lactic acid [Lac]) parameters, various critical disease scores, and incidence of complications after the treatment were compared between the two groups. RESULTS: Compared with those in the routine CRRT group, patients in the CRRT+PTGD group exhibited significant remission of clinical symptoms (i.e. shorter abdominal pain remission time, gastrointestinal decompression time, respirator treatment time and ICU hospital stay) (all P<0.05), change of laboratory parameters (WBC, PLT, PCT, CRP, TBIL, ALT) (P<0.05), and improvement of various critical disease scores (P<0.05). Moreover, the variation of most of the above parameters after versus before the treatment was greater in the CRRT+PTGD group than in the CRRT group (all P<0.05). CONCLUSION: CRRT in combination with PTGD is more effective in the treatment of ASBP than CRRT alone.


Assuntos
Drenagem/métodos , Vesícula Biliar/cirurgia , Pancreatite/terapia , Terapia de Substituição Renal/métodos , Doença Aguda , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
15.
Molecules ; 22(11)2017 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-29144401

RESUMO

In this work, a series of novel benzyl sulfoxide 2-indolinone derivatives was designed and synthesized as potent anticancer agents. Tyrosine kinase inhibitory activity assay indicated that most of the compounds showed significant activity. The in vitro antiproliferative activity of these compounds was further investigated against five human cancer cell lines (HeLa, HepG2, MCF-7, SCC-15, and A549). Several compounds exhibited evident activities. Among them, (Z)-3-(((4-bromobenzyl)sulfinyl)methylene)indolin-2-one (6j) and (Z)-3-((benzylsulfinyl)methylene)-5-bromoindolin-2-one (6o) were found to be effective tyrosine kinase inhibitors (IC50 = 1.34 and 2.69 µM, respectively) in addition to having noteworthy antitumor potential (the average IC50 value of 6j or 6o was less than 40 µM). This class of novel derivatives has promising potential for further development as anticancer agents.


Assuntos
Antineoplásicos/química , Oxindóis/química , Sulfóxidos/química , Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Oxindóis/síntese química , Oxindóis/farmacologia , Proteínas Tirosina Quinases/antagonistas & inibidores , Relação Estrutura-Atividade , Sulfóxidos/síntese química , Sulfóxidos/farmacologia
16.
Molecules ; 22(8)2017 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-28805748

RESUMO

A series of benzofuran derivatives were designed and synthesized, and their inhibitory activites were measured against the SIRT1-3. The enzymatic assay showed that all the compounds showed certain anti-SIRT2 activity and selective over SIRT1 and SIRT3 with IC50 (half maximal inhibitory concentration) values at the micromolar level. The preliminary structure-activity relationships were analyzed and the binding features of compound 7e (IC50 3.81 µM) was predicted using the CDOCKER program. The results of this research could provide informative guidance for further optimizing benzofuran derivatives as potent SIRT2 inhibitors.


Assuntos
Benzofuranos/síntese química , Benzofuranos/farmacologia , Técnicas de Química Sintética/métodos , Sirtuína 2/antagonistas & inibidores , Sítios de Ligação , Desenho de Fármacos , Escherichia coli , Expressão Gênica , Humanos , Espectroscopia de Ressonância Magnética/métodos , Espectrometria de Massas/métodos , Simulação de Acoplamento Molecular/métodos , Estrutura Molecular , Ligação Proteica , Sirtuína 2/genética , Relação Estrutura-Atividade
17.
Int Heart J ; 57(2): 241-6, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26973269

RESUMO

We investigated the effects of early rehabilitation therapy on prolonged mechanically ventilated patients after coronary artery bypass surgery (CABG).A total of 106 patients who underwent CABG between June 2012 and May 2015 were enrolled and randomly assigned into an early rehabilitation group (53 cases) and a control group (53 cases). The rehabilitation therapy consisted of 6 steps including head up, transferring from supination to sitting, sitting on the edge of bed, sitting in a chair, transferring from sitting to standing, and walking along a bed. The patients received rehabilitation therapy in the intensive care unit (ICU) after CABG in the early rehabilitation group. The control group patients received rehabilitation therapy after leaving the ICU.The results showed that the early rehabilitation therapy could significantly decrease the duration of mechanical ventilation (early rehabilitation group: 8.1 ± 3.3 days; control group: 13.9 ± 4.1 days, P < 0.01), hospital stay (early rehabilitation group: 22.0 ± 3.8 days; control group: 29.1 ± 4.6 days, P < 0.01), and ICU stay (early rehabilitation group: 11.7 ± 3.2 days; control group: 18.3 ± 4.2 days, P < 0.01) for patients requiring more than 72 hours prolonged mechanical ventilation. The results of Kaplan-Meier analysis showed that the proportions of patients remaining on mechanical ventilation in the early rehabilitation group were larger than that in the control group after 7 days of rehabilitation therapy (logrank test: P < 0.01). The results provide evidence for supporting the application of early rehabilitation therapy in patients requiring prolonged mechanical ventilation after CABG.


Assuntos
Ponte de Artéria Coronária/reabilitação , Doença da Artéria Coronariana/cirurgia , Modalidades de Fisioterapia , Respiração Artificial/métodos , Doença da Artéria Coronariana/reabilitação , Feminino , Seguimentos , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Prevenção Secundária , Fatores de Tempo , Resultado do Tratamento
18.
Carbohydr Polym ; 329: 121758, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38286539

RESUMO

In this study, a novel and accurate quantitative analysis method for the direct determination of chitosan (CS) in aqueous solutions using ultrahigh-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) is presented. By detecting the mass spectrum response intensity of a series of CS characteristic ion pairs, the sample concentration (abscissa) was linearly fitted with the total ion current (TIC) response intensity of its characteristic ion pairs (ordinate). A reliable standard curve was derived for quantifying CS in the range of 125-4000 ng/mL. Under the detection conditions, this CS quantification method yielded acceptable specificity (no interference peak), linearity (with correlation coefficient (r2) values >0.999), precision (acceptable limit RSDr < 3 %, RSDR < 6 %), accuracy (RE within the acceptable limits of ±5 %), and stability (acceptable limit RE within ±5 %, RSDr < 3 %). Moreover, the applicability of measurement was verified when a series of substrates did not interact with CS in the solution. Results have verified the applicability of this method for determining CS content in different composites. This study provides a method for determining CS content with significant practical value and economic benefit.


Assuntos
Quitosana , Espectrometria de Massas em Tandem , Cromatografia Líquida , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida de Alta Pressão/métodos
19.
Thromb Haemost ; 124(7): 599-612, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38242171

RESUMO

Sepsis represents a syndromic response to infection and frequently acts as a common pathway leading to fatality in the context of various infectious diseases globally. The pathology of severe sepsis is marked by an excess of inflammation and activated coagulation. A substantial contributor to mortality in sepsis patients is widespread microvascular thrombosis-induced organ dysfunction. Multiple lines of evidence support the notion that sepsis induces endothelial damage, leading to the release of glycosaminoglycans, potentially causing microvascular dysfunction. This review aims to initially elucidate the relationship among endothelial damage, excessive inflammation, and thrombosis in sepsis. Following this, we present a summary of the involvement of glycosaminoglycans in coagulation, elucidating interactions among glycosaminoglycans, platelets, and inflammatory cells. In this section, we also introduce a reasoned generalization of potential signal pathways wherein glycosaminoglycans play a role in clotting. Finally, we discuss current methods for detecting microvascular conditions in sepsis patients from the perspective of glycosaminoglycans. In conclusion, it is imperative to pay closer attention to the role of glycosaminoglycans in the mechanism of microvascular thrombosis in sepsis. Dynamically assessing glycosaminoglycan levels in patients may aid in predicting microvascular conditions, enabling the monitoring of disease progression, adjustment of clinical treatment schemes, and mitigation of both acute and long-term adverse outcomes associated with sepsis.


Assuntos
Coagulação Sanguínea , Glicosaminoglicanos , Sepse , Humanos , Sepse/sangue , Sepse/complicações , Glicosaminoglicanos/sangue , Animais , Plaquetas/metabolismo , Microvasos , Transdução de Sinais , Inflamação/sangue , Microcirculação , Trombose/sangue
20.
Int J Biol Macromol ; 272(Pt 2): 132923, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38848835

RESUMO

Severe bleeding from deep and irregular wounds poses a significant challenge in prehospital and surgical settings. To address this issue, we developed a novel chitosan-based hemostatic dressing with a magnetic targeting mechanism using Fe3O4, termed bovine serum albumin-modified Fe3O4 embedded in porous α-ketoglutaric acid/chitosan (BSA/Fe3O4@KA/CS). This dressing enhances hemostasis by magnetically guiding the agent to the wound site. In vitro, the hemostatic efficacy of BSA/Fe3O4@KA/CS is comparable to that of commercial chitosan (Celox™) and is not diminished by the modification. In vivo, BSA/Fe3O4@KA/CS demonstrated superior hemostatic performance and reduced blood loss compared to Celox™. The hemostatic mechanism of BSA/Fe3O4@KA/CS includes the concentration of solid blood components through water absorption, adherence to blood cells, and activation of the endogenous coagulation pathway. Magnetic field targeting is crucial in directing the dressing to deep hemorrhagic sites. Additionally, safety assessments have confirmed the biocompatibility and biodegradability of BSA/Fe3O4@KA/CS. In conclusion, we introduce a novel approach to modify chitosan using magnetic guidance for effective hemostasis, positioning BSA/Fe3O4@KA/CS as a promising candidate for managing various wounds.


Assuntos
Bandagens , Quitosana , Hemostáticos , Soroalbumina Bovina , Quitosana/química , Soroalbumina Bovina/química , Animais , Hemostáticos/química , Hemostáticos/farmacologia , Porosidade , Ácidos Cetoglutáricos/química , Ácidos Cetoglutáricos/farmacologia , Bovinos , Masculino , Hemorragia/tratamento farmacológico , Hemorragia/terapia , Camundongos
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