Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 90
Filter
Add more filters

Country/Region as subject
Affiliation country
Publication year range
1.
Biopharm Drug Dispos ; 45(3): 149-158, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38886878

ABSTRACT

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.


Subject(s)
Drug Interactions , Flavonoids , Glucuronosyltransferase , Microsomes, Liver , Glucuronosyltransferase/antagonists & inhibitors , Glucuronosyltransferase/metabolism , Humans , Flavonoids/pharmacology , Microsomes, Liver/metabolism , Estradiol/pharmacology , Hymecromone/pharmacology , Propofol/pharmacology , Enzyme Inhibitors/pharmacology
2.
Int J Mol Sci ; 25(2)2024 Jan 06.
Article in English | MEDLINE | ID: mdl-38255822

ABSTRACT

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.


Subject(s)
Animal Experimentation , Sepsis , Animals , Humans , Mice , Biomarkers , Cell Adhesion , Computational Biology , Disease Models, Animal , Sepsis/genetics
3.
Molecules ; 29(2)2024 Jan 22.
Article in English | MEDLINE | ID: mdl-38276624

ABSTRACT

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.


Subject(s)
Antineoplastic Agents , Colorectal Neoplasms , Humans , Animals , Mice , Tissue Distribution , Antibodies, Monoclonal , ErbB Receptors/metabolism , Colorectal Neoplasms/drug therapy , Cell Line, Tumor
4.
Cell Commun Signal ; 21(1): 34, 2023 02 13.
Article in English | MEDLINE | ID: mdl-36782203

ABSTRACT

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.


Subject(s)
Cognition , Microwaves , Cognition/radiation effects , Hippocampus/metabolism , Hippocampus/radiation effects , Microwaves/adverse effects , Animals
5.
Molecules ; 28(16)2023 Aug 18.
Article in English | MEDLINE | ID: mdl-37630371

ABSTRACT

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.


Subject(s)
Astragalus Plant , Saponins , Triterpenes , Saponins/pharmacology , Triterpenes/pharmacology , Cell Proliferation
6.
Molecules ; 28(21)2023 Nov 06.
Article in English | MEDLINE | ID: mdl-37959868

ABSTRACT

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.


Subject(s)
Hyaluronic Acid , Skin , Hyaluronic Acid/pharmacology , Skin/metabolism , Oxidative Stress , Reactive Oxygen Species/metabolism , Oxidation-Reduction
7.
Ecotoxicol Environ Saf ; 243: 113983, 2022 Sep 15.
Article in English | MEDLINE | ID: mdl-35985199

ABSTRACT

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.


Subject(s)
Exosomes , Microwaves , Animals , Blood Proteins/metabolism , Hippocampus , Male , Maze Learning , Microwaves/adverse effects , Rats , Rats, Wistar , Spatial Learning
8.
Endocr Res ; 47(1): 32-38, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34409914

ABSTRACT

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.


Subject(s)
COVID-19 , Diabetes Mellitus , Diabetes Mellitus/drug therapy , Humans , Insulin , Observational Studies as Topic , SARS-CoV-2
9.
Molecules ; 27(7)2022 Mar 29.
Article in English | MEDLINE | ID: mdl-35408630

ABSTRACT

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.


Subject(s)
Peptides, Cyclic , Solid-Phase Synthesis Techniques , Photolysis
10.
Zhongguo Zhong Yao Za Zhi ; 46(17): 4334-4343, 2021 Sep.
Article in Zh | MEDLINE | ID: mdl-34581036

ABSTRACT

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.


Subject(s)
Sapindaceae , Triterpenes , Anti-Inflammatory Agents , Flavonoids , Research
11.
Chem Pharm Bull (Tokyo) ; 68(5): 443-446, 2020 May 01.
Article in English | MEDLINE | ID: mdl-32173668

ABSTRACT

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.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Coumarins/pharmacology , Cyclooxygenase Inhibitors/pharmacology , Drug Design , Ear Diseases/drug therapy , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Animals , Anti-Inflammatory Agents, Non-Steroidal/chemical synthesis , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Cell Survival/drug effects , Coumarins/chemical synthesis , Coumarins/chemistry , Cyclooxygenase 1/metabolism , Cyclooxygenase 2/metabolism , Cyclooxygenase Inhibitors/chemical synthesis , Cyclooxygenase Inhibitors/chemistry , Dose-Response Relationship, Drug , Ear Diseases/chemically induced , Lipopolysaccharides/antagonists & inhibitors , Lipopolysaccharides/pharmacology , Macrophages/drug effects , Mice , Molecular Structure , RAW 264.7 Cells , Structure-Activity Relationship , Tumor Necrosis Factor-alpha/biosynthesis , Xylenes
12.
Molecules ; 24(22)2019 Nov 07.
Article in English | MEDLINE | ID: mdl-31703373

ABSTRACT

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.


Subject(s)
Antineoplastic Agents , Class I Phosphatidylinositol 3-Kinases/antagonists & inhibitors , Coumarins , Drug Design , Enzyme Inhibitors , Molecular Docking Simulation , Neoplasm Proteins/antagonists & inhibitors , Neoplasms/drug therapy , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Class I Phosphatidylinositol 3-Kinases/metabolism , Coumarins/chemical synthesis , Coumarins/chemistry , Coumarins/pharmacology , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/pharmacology , HCT116 Cells , HeLa Cells , Hep G2 Cells , Humans , MCF-7 Cells , Neoplasm Proteins/metabolism , Neoplasms/enzymology
13.
BMC Anesthesiol ; 18(1): 168, 2018 11 13.
Article in English | MEDLINE | ID: mdl-30424730

ABSTRACT

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.


Subject(s)
Blood Flow Velocity/physiology , Catheterization, Peripheral/trends , Fluid Therapy/trends , Respiration, Artificial/trends , Respiratory Mechanics/physiology , Catheterization, Peripheral/methods , Fluid Therapy/adverse effects , Forecasting , Humans , Respiration, Artificial/methods , Treatment Outcome , Ventilators, Mechanical/trends
14.
Kidney Blood Press Res ; 42(6): 1023-1032, 2017.
Article in English | MEDLINE | ID: mdl-29212080

ABSTRACT

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.


Subject(s)
Drainage/methods , Gallbladder/surgery , Pancreatitis/therapy , Renal Replacement Therapy/methods , Acute Disease , Adult , Aged , Female , Humans , Male , Middle Aged , Retrospective Studies , Treatment Outcome
15.
Molecules ; 22(11)2017 Nov 16.
Article in English | MEDLINE | ID: mdl-29144401

ABSTRACT

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.


Subject(s)
Antineoplastic Agents/chemistry , Oxindoles/chemistry , Sulfoxides/chemistry , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacology , Cell Line, Tumor , Cell Survival/drug effects , Drug Screening Assays, Antitumor , Humans , Oxindoles/chemical synthesis , Oxindoles/pharmacology , Protein-Tyrosine Kinases/antagonists & inhibitors , Structure-Activity Relationship , Sulfoxides/chemical synthesis , Sulfoxides/pharmacology
16.
Molecules ; 22(8)2017 Aug 14.
Article in English | MEDLINE | ID: mdl-28805748

ABSTRACT

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.


Subject(s)
Benzofurans/chemical synthesis , Benzofurans/pharmacology , Chemistry Techniques, Synthetic/methods , Sirtuin 2/antagonists & inhibitors , Binding Sites , Drug Design , Escherichia coli , Gene Expression , Humans , Magnetic Resonance Spectroscopy/methods , Mass Spectrometry/methods , Molecular Docking Simulation/methods , Molecular Structure , Protein Binding , Sirtuin 2/genetics , Structure-Activity Relationship
17.
Int Heart J ; 57(2): 241-6, 2016.
Article in English | MEDLINE | ID: mdl-26973269

ABSTRACT

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.


Subject(s)
Coronary Artery Bypass/rehabilitation , Coronary Artery Disease/surgery , Physical Therapy Modalities , Respiration, Artificial/methods , Coronary Artery Disease/rehabilitation , Female , Follow-Up Studies , Humans , Length of Stay , Male , Middle Aged , Retrospective Studies , Risk Factors , Secondary Prevention , Time Factors , Treatment Outcome
18.
Heliyon ; 10(16): e35988, 2024 Aug 30.
Article in English | MEDLINE | ID: mdl-39247343

ABSTRACT

Following the coronavirus disease-2019 outbreak caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), there is an ongoing need to seek drugs that target COVID-19. First off, novel drugs have a long development cycle, high investment cost, and are high risk. Second, novel drugs must be evaluated for activity, efficacy, safety, and metabolic performance, contributing to the development cycle, investment cost, and risk. We searched the Cochrane COVID-19 Study Register (including PubMed, Embase, CENTRAL, ClinicalTrials.gov, WHO ICTRP, and medRxiv), Web of Science (Science Citation Index, Emerging Citation Index), and WHO COVID-19 Coronaviral Disease Global Literature to identify completed and ongoing studies as of February 20, 2024. We evaluated the pharmacological effects, in vivo and in vitro data of the 16 candidates in the paper. The difficulty of studying these candidates in clinical trials involving COVID-19 patients, dosage of repurposed drugs, etc. is discussed in detail. Ultimately, Metformin is more suitable for prophylactic administration or mildly ill patients; the combination of Oseltamivir, Tamoxifen, and Dexamethasone is suitable for moderately and severely ill patients; and more clinical trials are needed for Azvudine, Ribavirin, Colchicine, and Cepharanthine to demonstrate efficacy.

19.
Sci Rep ; 14(1): 15589, 2024 07 06.
Article in English | MEDLINE | ID: mdl-38971879

ABSTRACT

Federated learning (FL) has emerged as a significant method for developing machine learning models across multiple devices without centralized data collection. Candidemia, a critical but rare disease in ICUs, poses challenges in early detection and treatment. The goal of this study is to develop a privacy-preserving federated learning framework for predicting candidemia in ICU patients. This approach aims to enhance the accuracy of antifungal drug prescriptions and patient outcomes. This study involved the creation of four predictive FL models for candidemia using data from ICU patients across three hospitals in China. The models were designed to prioritize patient privacy while aggregating learnings across different sites. A unique ensemble feature selection strategy was implemented, combining the strengths of XGBoost's feature importance and statistical test p values. This strategy aimed to optimize the selection of relevant features for accurate predictions. The federated learning models demonstrated significant improvements over locally trained models, with a 9% increase in the area under the curve (AUC) and a 24% rise in true positive ratio (TPR). Notably, the FL models excelled in the combined TPR + TNR metric, which is critical for feature selection in candidemia prediction. The ensemble feature selection method proved more efficient than previous approaches, achieving comparable performance. The study successfully developed a set of federated learning models that significantly enhance the prediction of candidemia in ICU patients. By leveraging a novel feature selection method and maintaining patient privacy, the models provide a robust framework for improved clinical decision-making in the treatment of candidemia.


Subject(s)
Candidemia , Intensive Care Units , Machine Learning , Humans , Candidemia/drug therapy , Candidemia/diagnosis , Antifungal Agents/therapeutic use , China , Male , Female , Delivery of Health Care
20.
Polymers (Basel) ; 16(6)2024 Mar 21.
Article in English | MEDLINE | ID: mdl-38543468

ABSTRACT

A traumatic hemorrhage is fatal due to the great loss of blood in a short period of time; however, there are a few biomaterials that can stop the bleeding quickly due to the limited water absorption speed. Here, a highly absorbent polymer (HPA), polyacrylate, was prepared as it has the best structure-effectiveness relationship. Within a very short period of time (2 min), HPA continually absorbed water until it swelled up to its 600 times its weight; more importantly, the porous structure comprised the swollen dressing. This instantaneous swelling immediately led to rapid hemostasis in irregular wounds. We optimized the HPA preparation process to obtain a rapidly water-absorbent polymer (i.e., HPA-5). HPA-5 showed favorable adhesion and biocompatibility in vitro. A rat femoral arteriovenous complete shear model and a tail arteriovenous injury model were established. HPA exhibited excellent hemostatic capability with little blood loss and short hemostatic time compared with CeloxTM in both of the models. The hemostatic mechanisms of HPA consist of fast clotting by aggregating blood cells, activating platelets, and accelerating the coagulation pathway via water absorption and electrostatic interaction. HPA is a promising highly water-absorbent hemostatic dressing for rapid and extensive blood clotting after vessel injury.

SELECTION OF CITATIONS
SEARCH DETAIL