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1.
Plant Foods Hum Nutr ; 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38985368

RESUMO

The study wanted to explore the preventative effects of Aornia melanocarpa Elliot anthocyanins (AMA) to Alcoholic liver disease (ALD) by bioinformatics prediction and experimental verification. We founded 419 differentially expressed genes (DEGs) in GSE28619 related to ALD from GEO database, COL1A1 was selected by the core gene module construction and molecular docking. Mice were treated by intragastric administration of gradient 50% ethanol, AMA alleviated liver injury by ALD and ameliorated the model's body weight, lessened the liver inflammation according to histopathological evaluation, increased serum liver biochemical index (AST, ALT, TC, TG and LDL-C) and decreased HDL-C, reversed the expression of enzymes (ALDH and GSH-PX), decreased cytokines expression (Ki67, TNF-α and IL-6), reversed the expression of α7nAChR and collagen I, downregulated the PI3K-Akt pathway and Keap1/HO-1 pathway (p-PI3K, PI3K, p-Akt, Akt, Keap1, Nrf2, HO-1,GSK-3ß and Bcl-2), indicated that α7nAChR and collagen I may be the AMA action targets.

2.
Small ; : e2401061, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38963320

RESUMO

The precise mapping of collateral circulation and ischemic penumbra is crucial for diagnosing and treating acute ischemic stroke (AIS). Unfortunately, there exists a significant shortage of high-sensitivity and high-resolution in vivo imaging techniques to fulfill this requirement. Herein, a contrast enhanced susceptibility-weighted imaging (CE-SWI) using the minimalist dextran-modified Fe3O4 nanoparticles (Fe3O4@Dextran NPs) are introduced for the highly sensitive and high-resolution AIS depiction under 9.4 T for the first time. The Fe3O4@Dextran NPs are synthesized via a simple one-pot coprecipitation method using commercial reagents under room temperature. It shows merits of small size (hydrodynamic size 25.8 nm), good solubility, high transverse relaxivity (r2) of 51.3 mM-1s-1 at 9.4 T, and superior biocompatibility. The Fe3O4@Dextran NPs-enhanced SWI can highlight the cerebral vessels readily with significantly improved contrast and ultrahigh resolution of 0.1 mm under 9.4 T MR scanner, enabling the clear spatial identification of collateral circulation in the middle cerebral artery occlusion (MCAO) rat model. Furthermore, Fe3O4@Dextran NPs-enhanced SWI facilitates the precise depiction of ischemia core, collaterals, and ischemic penumbra post AIS through matching analysis with other multimodal MR sequences. The proposed Fe3O4@Dextran NPs-enhanced SWI offers a high-sensitivity and high-resolution imaging tool for individualized characterization and personally precise theranostics of stroke patients.

3.
Ther Drug Monit ; 46(4): 422-433, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38840327

RESUMO

BACKGROUND: This meta-analysis aims to investigate the efficacy and safety of programmed death 1 (PD-1)/programmed death-ligand 1 (PD-L1) combined with cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) inhibitors for patients with advanced or metastatic non-small cell lung cancer (NSCLC). METHODS: Authors conducted a comprehensive search of PubMed, Embase, Cochrane Library, Web of Science, Scopus, and Medline for randomized controlled trials comparing the prognosis and safety of PD-1/PD-L1 plus CTLA-4 inhibitors with other therapies for advanced or metastatic NSCLC. Hazard ratios (HRs) and 95% confidence intervals (CIs) were used as effect sizes. The primary outcomes of this study were overall survival (OS) and progression-free survival. RESULTS: A total of 4943 patients diagnosed with stage III/IV advanced or metastatic NSCLC were included in the analysis of the 6 randomized controlled trials. The results showed that patients receiving dual immunotherapy with PD-1/PD-L1 plus CTLA-4 inhibitors had a longer survival time compared with the control group (HR = 0.88, P = 0.044). However, no statistically significant difference was observed in progression-free survival (HR = 0.95, P = 0.579). Subgroup analysis revealed better OS in the interventional group for patients aged >65 years (HR = 0.88, P = 0.076), smokers (HR = 0.81, P = 0.036), and those with a tumor mutational burden (TMB) ≥20 mut/Mb (HR = 0.66, P < 0.001). Conversely, the control group demonstrated superior OS in patients with TMB <20 mut/Mb (HR = 1.14, P = 0.048). In addition, the statistical results indicated a lower incidence rate of any-grade anemia in the dual immunotherapy group compared with the control group (RR = 0.32, P = 0.04). CONCLUSIONS: This meta-analysis demonstrates the effectiveness and safety of dual immunotherapy with PD-1/PD-L1 plus CTLA-4 inhibitors for treating advanced or metastatic NSCLC. Its efficacy is influenced by certain clinical and pathological factors, such as age, smoking status, and TMB.


Assuntos
Antígeno B7-H1 , Antígeno CTLA-4 , Carcinoma Pulmonar de Células não Pequenas , Inibidores de Checkpoint Imunológico , Neoplasias Pulmonares , Receptor de Morte Celular Programada 1 , Ensaios Clínicos Controlados Aleatórios como Assunto , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Antígeno CTLA-4/antagonistas & inibidores , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Antígeno B7-H1/antagonistas & inibidores , Inibidores de Checkpoint Imunológico/uso terapêutico , Imunoterapia/métodos
4.
J Chromatogr A ; 1728: 464991, 2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-38788322

RESUMO

The abnormal estrogens levels in human body can cause many side effects and diseases, but the quantitative detection of the trace estrogens in complex biological samples still remains great challenge. Here we reported the fabrication of a novel core-shell structured magnetic cyclodextrin microporous organic network (Fe3O4@CD-MON) for rapid magnetic solid phase extraction (MSPE) of four estrogens in human serum and urine samples prior to HPLC-UV determination. The uniform spherical core-shell Fe3O4@CD-MONs was successfully regulated by altering the reactive monomers and solvents. The Fe3O4@CD-MONs owned high specific surface area, good hydrophobicity, large superparamagnetism, and abundant extraction sites for estrogens. Under optimal conditions, the proposed MSPE-HPLC-UV method provided wide linearity range (2.0-400 µg L-1), low limits of detection (0.5-1.0 µg L-1), large enrichment factors (183-198), less adsorbent consumption (3 mg), short extraction time (3 min), and good stability and reusability (at least 8 cycles). The established method had also been successfully applied to the enrichment and detection of four estrogens in serum and urine samples with a recovery of 88.4-105.1 % and a relative standard deviation of 1.0-5.9 %. This work confirmed the feasibility of solvent and monomer regulation synthesis of Fe3O4@CD-MON composites, and revealed the great prospects of magnetic CD-MONs for efficient enrichment of trace estrogens in complex biological samples.


Assuntos
Estrogênios , Limite de Detecção , Extração em Fase Sólida , beta-Ciclodextrinas , Humanos , Cromatografia Líquida de Alta Pressão/métodos , Estrogênios/urina , Estrogênios/sangue , Estrogênios/isolamento & purificação , Estrogênios/análise , Estrogênios/química , Extração em Fase Sólida/métodos , beta-Ciclodextrinas/química , Solventes/química , Porosidade , Nanopartículas de Magnetita/química , Adsorção
5.
Zhongguo Zhong Yao Za Zhi ; 49(10): 2776-2782, 2024 May.
Artigo em Chinês | MEDLINE | ID: mdl-38812178

RESUMO

This study explore the molecular mechanism of the synergistic effect of Chinese Yam polysaccharides and nucleoside analogues(NAs) on hepatitis B virus(HBV) resistance. Different concentrations of Chinese Yam polysaccharide and entecavir were ad-ded to HepG2.2.15 cells. After the cytotoxicity was detected by cell counting kit-8(CCK-8), the optimal concentration and time of the two drugs to inhibit HepG2.2.15 cells were screened out. They were divided into control group, Chinese Yam polysaccharide group, entecavir group and combination drug group(Chinese Yam polysaccharide + entecavir). The drugs were added to HepG2.2.15 cells, ELISA was used to detect the effects of each group of drugs on the secretion of hepatitis B virus surface antigen(HBsAg) and hepatitis B virus e antigen(HBeAg) in cell supernatant, probe quantitative real-time PCR(probe qRT-PCR) was used to detect the effects of drugs on HBV-DNA in HepG2.2.15 cells, and Western blot was used to detect the effects of each group of drugs on the expression of p38 MAPK, p-p38 MAPK, NTCP proteins in HepG2.2.15 cells. The qRT-PCR was used to detect the effect of drugs on the expression of p38 MAPK and NTCP mRNA in HepG2.2.15 cells. The results showed that compared with control group, the concentrations of HBeAg and HBsAg in Chinese Yam polysaccharide group, entecavir group and combination group decreased(P<0.01 or P<0.001), and both of them inhibited HBV-DNA in HepG2.2.15 cells(P<0.01), and the HBV-DNA inhibition of HepG2.2.15 cells in the combination group was more obvious(P<0.001), and the protein expression levels of p-p38 MAPK and NTCP were significantly decreased(P<0.05 or P<0.01), the mRNA expression level of p38 MAPK increased, and the mRNA expression level of NTCP decreased(P<0.05 or P<0.01). To sum up, Chinese Yam polysaccharide can reduce the expression of NTCP protein and mRNA through p38 MAPK signaling pathway and cooperate with entecavir in anti-HBV.


Assuntos
Antivirais , Dioscorea , Vírus da Hepatite B , Polissacarídeos , Proteínas Quinases p38 Ativadas por Mitógeno , Humanos , Vírus da Hepatite B/efeitos dos fármacos , Vírus da Hepatite B/genética , Polissacarídeos/farmacologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Células Hep G2 , Antivirais/farmacologia , Dioscorea/química , Sinergismo Farmacológico , Nucleosídeos/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Antígenos de Superfície da Hepatite B/metabolismo , Antígenos de Superfície da Hepatite B/genética , Antígenos E da Hepatite B/metabolismo , Hepatite B/tratamento farmacológico , Hepatite B/virologia , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/química , Guanina/análogos & derivados , Guanina/farmacologia
6.
Int Arch Allergy Immunol ; 185(6): 590-599, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38432201

RESUMO

INTRODUCTION: A growing number of randomized controlled trials (RCTs) have demonstrated the effectiveness of tumor necrosis factor-α (TNF-α) inhibitors in treating non-radiographic axial spondyloarthritis (nr-axSpA). This study aimed to evaluate the efficacy of TNF-α inhibitors in the treatment of nr-axSpA. METHODS: PubMed, EMBASE, Web of Science, and the Cochrane Library databases were systematically searched for relevant RCTs using specific keywords up to June 2023. The primary outcome was the proportion of patients who achieved Assessment in SpondyloArthritis international Society 40% (ASAS40). Secondary outcomes included ASAS20, Bath Ankylosing Spondylitis Disease Activity Index 50% (BASDAI50), ASAS partial remission, and ASAS5/6. RESULTS: A total of eight RCTs involving 1,376 patients were included. Patients receiving anti-TNF therapy exhibited a higher rate of ASAS40 (pooled RR = 2.36; 95% CI: 1.63-3.42; p < 0.001). In addition, the TNF-α inhibitor group showed higher BASDAI50 rates (pooled RR = 2.06; 95% CI: 1.48-2.89), ASAS20 rates (pooled RR = 1.48; 95% CI: 1.31-1.67), ASAS partial remission rates (pooled RR = 2.33; 95% CI: 1.58-3.43), and ASAS5/6 rates (RR = 3.46; 95% CI: 2.05-5.83) than the placebo group. CONCLUSION: The TNF-α inhibitors were effective in treating nr-axSpA.


Assuntos
Ensaios Clínicos Controlados Aleatórios como Assunto , Fator de Necrose Tumoral alfa , Humanos , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Resultado do Tratamento , Espondilartrite/tratamento farmacológico , Antirreumáticos/uso terapêutico , Espondilite Anquilosante/tratamento farmacológico
7.
J Pharm Pharmacol ; 76(4): 416-425, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38402632

RESUMO

OBJECTIVES: Orientation to specific cells is an important topic in active targeting strategy for nanoparticle-based drug delivery systems. While these administered nanoparticles will be sequestrated within the liver, their cellular distribution behaviors in the liver are not clear. The aim of this study was to fabricate glycyrrhizic acid (GL) modified BSA nanoparticles and evaluate their hepatic cellular distribution. METHODS: GL-modified BSA (GL-BSA) was tailored according to the periodate oxidation method, then GL-BSA nanoparticles loaded with paclitaxel (PTX@GL-BSA NPs) were prepared through self-assembly approach. In vitro cellular uptake was assessed by FITC-labeled BSA nanoparticles and immunofluorescent analysis was performed to track their relative distribution in the liver. KEY FINDINGS: The fabricated PTX@GL-BSA NPs were spherical structure with the particle size of 179 nm and a negative potential (-17.3 mV). Flow cytometry (FCM) studies exhibited that the accumulation of GL-BSA nanoparticles was 5.3-fold compared with BSA nanoparticles in HepG2 cells. The Nanoparticles were preferentially accumulated in the sinusoidal endothelial cells rather than the Kupffer cells. CONCLUSIONS: This study provides useful information to understand the distribution of hepatic targeting nanoparticles when using GL-modified BSA nanoparticles, which helps to further use for effective treatment of liver disease.


Assuntos
Ácido Glicirrízico , Nanopartículas , Portadores de Fármacos/química , Células Endoteliais , Soroalbumina Bovina/química , Hepatócitos , Nanopartículas/química , Tamanho da Partícula
8.
J Control Release ; 366: 732-745, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38242209

RESUMO

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with high mortality. The Food and Drug Administration-approved drugs, nintedanib and pirfenidone, could delay progressive fibrosis by inhibiting the overactivation of fibroblast, however, there was no significant improvement in patient survival due to low levels of drug accumulation and remodeling of honeycomb cyst and interstitium surrounding the alveoli. Herein, we constructed a dual drug (verteporfin and pirfenidone)-loaded nanoparticle (Lip@VP) with the function of inhibiting airway epithelium fluidization and fibroblast overactivation to prevent honeycomb cyst and interstitium remodeling. Specifically, Lip@VP extensively accumulated in lung tissues via atomized inhalation. Released verteporfin inhibited the fluidization of airway epithelium and the formation of honeycomb cyst, and pirfenidone inhibited fibroblast overactivation and reduced cytokine secretion that promoted the fluidization of airway epithelium. Our results indicated that Lip@VP successfully rescued lung function through inhibiting honeycomb cyst and interstitium remodeling. This study provided a promising strategy to improve the therapeutic efficacy for IPF.


Assuntos
Cistos , Fibrose Pulmonar Idiopática , Nanopartículas , Humanos , Verteporfina , Fibrose Pulmonar Idiopática/tratamento farmacológico , Pulmão
9.
Support Care Cancer ; 32(2): 140, 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38294563

RESUMO

BACKGROUND: This study aims to investigate the effect of PD-1/PD-L1 immunotherapy on cardiac-related adverse events in patients with advanced or metastatic lung cancer. METHODS: We conducted a detailed search in PubMed, Web of Science, Cochran, and Embase for articles on the application of immunotherapy for lung cancer and report cardiac-related adverse events with respect to myocardial ischemia, pericardial effusion, myocarditis, and electrophysiology. The dichotomous variables were assessed by relative risk (RR) and 95% confidence intervals (CI). RESULTS: A total of 7132 subjects were included in 12 phase III randomized controlled trials (RCTs). The results showed that under the fixed effects model, the probability of cardiac-related adverse events in pericardial effusion was higher in the experimental group than in the control group (RR 2.30, 95% CI 1.01-5.21, P = 0.05). Under the random effects model, there was no statistical difference between the two groups (RR 2.03, 95% CI 0.81-5.12, P = 0.13). No statistical difference is observed between the experimental group and the control group (under the fixed effects model and the random effects model) for other cardiac-related adverse events, including myocarditis, acute coronary syndrome, myocardial infarction, acute myocardial infarction, myocardial ischemia, unstable angina, ventricular tachycardia, supraventricular tachycardia, tachycardia, bradycardia, atrial flutter, atrial fibrillation, cardiac failure, cardiac arrest, cardiopulmonary failure, acute heart failure, cardiac arrest (all P > 0.05). CONCLUSIONS: PD-1/PD-L1 immunotherapy in advanced or metastatic lung cancer is generally safe for cardiac-related adverse events.


Assuntos
Insuficiência Cardíaca , Neoplasias Pulmonares , Isquemia Miocárdica , Miocardite , Derrame Pericárdico , Humanos , Receptor de Morte Celular Programada 1 , Antígeno B7-H1 , Neoplasias Pulmonares/terapia , Imunoterapia/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto
10.
Br J Nutr ; 131(1): 63-72, 2024 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-37424288

RESUMO

The purpose of this study is to further investigate the relationship between sweetener exposure and the risk of endometrial cancer (EC). Up until December 2022, a literature search in an electronic database was carried out utilizing PubMed, Web of Science, Ovid, and Scopus. The odds ratio (OR) and 95 % confidence interval (CI) were used to evaluate the results. Sweeteners were divided into nutritional sweeteners (generally refers to sugar, such as sucrose and glucose) and non-nutritional sweeteners (generally refers to artificial sweeteners, such saccharin and aspartame). Ten cohort studies and two case-control studies were eventually included. The study found that in 12 studies, compared with the non-exposed group, the incidence rate of EC in the sweetener exposed group was higher (OR = 1·15, 95 % CI = [1·07, 1·24]). Subgroup analysis showed that in 11 studies, the incidence rate of EC in the nutritional sweetener exposed group was higher than that in the non-exposed group (OR = 1·25, 95 % CI = [1·14, 1·38]). In 4 studies, there was no difference in the incidence rate of EC between individuals exposed to non-nutritional sweeteners and those who were not exposed to non-nutritional sweeteners (OR = 0·90, 95 % CI = [0·81, 1·01]). This study reported that the consumption of nutritional sweeteners may increase the risk of EC, whereas there was no significant relationship between the exposure of non-nutritional sweeteners and the incidence of EC. Based on the results of this study, it is recommended to reduce the intake of nutritional sweeteners, but it is uncertain whether use of on-nutritional sweeteners instead of nutritional sweetener.


Assuntos
Neoplasias do Endométrio , Adoçantes não Calóricos , Feminino , Humanos , Aspartame/efeitos adversos , Neoplasias do Endométrio/epidemiologia , Neoplasias do Endométrio/etiologia , Adoçantes não Calóricos/efeitos adversos , Sacarina/efeitos adversos , Sacarose/efeitos adversos , Edulcorantes/efeitos adversos , Estudos Observacionais como Assunto
11.
Arch Gynecol Obstet ; 309(2): 439-455, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-37219611

RESUMO

PURPOSE: This study was conducted to investigate the relationship between cesarean section (CS) offspring and autism spectrum disorders (ASD)/attention deficit hyperactivity disorder (ADHD). METHODS: Searching of the databases (PubMed, Web of Science, Embase, and Cochrane Library) for studies on the relationship between mode of delivery and ASD/ADHD until August 2022. The primary outcome was the incidence of ASD/ADHD in the offspring. RESULTS: This meta-analysis included 35 studies (12 cohort studies and 23 case-control studies). Statistical results showed a higher risk of ASD (odds ratio (OR) = 1.25, P < 0.001) and ADHD (OR = 1.11, P < 0.001) in CS offspring compared to the VD group. Partial subgroup analysis showed no difference in ASD risk between CS and VD offspring in sibling-matched groups (OR = 0.98, P = 0.625). The risk of ASD was higher in females (OR = 1.66, P = 0.003) than in males (OR = 1.17, P = 0.004) in the CS offspring compared with the VD group. There was no difference in the risk of ASD between CS under regional anesthesia group and VD group (OR = 1.07, P = 0.173). However, the risk of ASD was higher in the CS offspring under general anesthesia than in the VD offspring (OR = 1.62, P < 0.001). CS offspring developed autism (OR = 1.38, P = 0.011) and pervasive developmental disorder-not otherwise specified (OR = 1.46, P = 0.004) had a higher risk than VD offspring, but there was no difference in Asperger syndrome (OR = 1.19, P = 0.115). Offspring born via CS had a higher incidence of ADHD in different subgroup analyses (sibling-matched, type of CS, and study design). CONCLUSIONS: In this meta-analysis, CS was a risk factor for ASD/ADHD in offspring compared with VD.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Transtorno do Espectro Autista , Masculino , Humanos , Feminino , Gravidez , Cesárea/efeitos adversos , Transtorno do Espectro Autista/etiologia , Transtorno do Espectro Autista/complicações , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Transtorno do Deficit de Atenção com Hiperatividade/etiologia , Irmãos , Fatores de Risco
12.
Chem Commun (Camb) ; 59(99): 14677-14680, 2023 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-37997154

RESUMO

Combining the Hg2+-induced oxidization of silver nanoparticles with the cation exchange reaction between Ag+ and CuS nanoparticles for cascade signal amplification, a sensitive, universal and label-free ICP-MS bioassay for nucleic acids and proteins was developed. By replacing the loop sequence of the T-Hg-T hairpin structure with specific sequences or aptamers to different biomarkers, it has great promise for the early detection of biomarkers potentially for diagnosis of cancerous diseases.


Assuntos
Técnicas Biossensoriais , Mercúrio , Nanopartículas Metálicas , DNA/química , Hibridização de Ácido Nucleico , Prata/química , Nanopartículas Metálicas/química , Espectrometria de Fluorescência , Mercúrio/química , Cátions , Limite de Detecção , Biomarcadores
13.
World J Surg Oncol ; 21(1): 340, 2023 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-37880688

RESUMO

BACKGROUND: Adding anti-epidermal growth factor receptor (anti-EGFR) target agents to conversion therapy may improve the resection rates and survival of patients with potentially resectable metastatic colorectal cancer (mCRC). This study aims to analyze the efficacy and safety of additional anti-EGFR target agents. METHODS: A systematic search was conducted on PubMed, Web of Science, Embase, and Cochrane Library. And all relevant studies published in English before January 2023 were collected to explore the impact of additional anti-EGFR targeted agent on the efficacy and safety of patients with potentially resectable mCRC (PROSPERO: CRD42022340523, https://www.crd.york.ac.uk/PROSPERO/ ). RESULTS: This study included a total of 8 articles, including 2618 patients. The overall response rate (ORR) and R0 resection rates of the experimental group were higher than those of the control group, while there was no significant difference in progression-free survival (PFS) and overall survival (OS) between the two groups. In RAS/KRAS wild-type patients, the ORR (RR: 1.20, 95% Cl: 1.02-1.41, p = 0.03), R0 resection rate (RR: 1.60, 95% Cl: 1.17-2.20, p = 0.003), PFS (HR: 0.80, 95% Cl: 0.68-0.93, p = 0.003), and OS (HR: 0.87, 95% Cl: 0.76-0.99, p = 0.031) of the experimental group were higher than those of the control group. While in KRAS mutant patients, there was no statistical difference between the two groups in ORR, R0 resection rate, PFS, and OS. CONCLUSION: The addition of anti-EGFR targeted agents can improve the prognosis of RAS/KRAS wild-type patients with potentially resectable mCRC, while KRAS mutant patients may not benefit. In addition, the overall safety factor was controllable.


Assuntos
Neoplasias Colorretais , Humanos , Anticorpos Monoclonais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica , Cetuximab/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/cirurgia , Receptores ErbB/antagonistas & inibidores , Proteínas Proto-Oncogênicas p21(ras)/genética , Ensaios Clínicos Controlados Aleatórios como Assunto , Metástase Neoplásica
14.
Sheng Wu Gong Cheng Xue Bao ; 39(10): 4189-4203, 2023 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-37877399

RESUMO

Silver nanoparticles (AgNPs) is known as one of the most valuable metal nanoparticles in antibacterial and anticancer application. AgNPs-resistant bacteria has been documented, but it is unclear whether cancer cells can also escape the anti-cancer effect of AgNPs. In this study, we aimed to investigate this phenomenon and its underlying mechanism. The antibacterial activity and cytotoxicity of AgNPs were measured in the presence of HeLa cell metabolites. The status of AgNPs in the system associated with metabolites were characterized by UV-Vis, Zetasizer Nano ZS, and transmission electron microscopy. Non-targeted metabolomics was used to reveal the metabolites components that bind with AgNPs. HeLa cells were injected intraperitoneally to establish the tumor-bearing mice model, and the stability of AgNPs in mice serum was analyzed. The results manifested that HeLa cell metabolites inhibited the anticancer and antibacterial effects of AgNPs in a dose-dependent manner by causing AgNPs aggregation. Effective metabolites that inhibited the biological activity of AgNPs were stable in 100 ℃, insoluble in chloroform, containing sulfur elements, and had a molecular weight less than 1 kDa in molecular weight. There were 115 compounds bound with AgNPs. In vitro experiments showed that AgNPs aggregation occurred only when the concentration of α-ketoglutarate (AKG) and glutathione (GSH) together reached a certain threshold. Interestingly, the concentration of AKG and GSH in HeLa cellular metabolites was 10 and 6 times higher than that in normal cervical epithelial cells, respectively, which explained why the threshold was reached. Furthermore, the stability of AgNPs in the serum of tumor-bearing mice decreased by 20% (P < 0.05) compared with the healthy mice. In conclusion, our study demonstrates that HeLa cells escaped the anti-cancer effect of AgNPs through the synergistic effect of AKG and GSH, suggesting the need to develop strategies to overcome this limitation.


Assuntos
Nanopartículas Metálicas , Prata , Humanos , Animais , Camundongos , Células HeLa , Prata/farmacologia , Ácidos Cetoglutáricos/farmacologia , Antibacterianos/farmacologia , Glutationa , Testes de Sensibilidade Microbiana
15.
J Agric Food Chem ; 2023 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-37906521

RESUMO

Triacylglycerols (TAG) from microalgae can be used as feedstocks for biofuel production to address fuel shortages. Most of the current research has focused on the enzymes involved in TAG biosynthesis. In this study, the effects of malic enzyme (ME), which provides precursor and reducing power for TAG biosynthesis, on biomass and lipid accumulation and its response to salt stress in Dunaliella salina were investigated. The overexpression of DsME1 and DsME2 improved the lipid production, which reached 0.243 and 0.253 g/L and were 30.5 and 36.3% higher than wild type, respectively. The transcript levels of DsME1 and DsME2 increased with increasing salt concentration (0, 1, 2, 3, and 4.5 mol/L NaCl), indicating that DsMEs participated in the salt stress response in D. salina. It was found that cis-acting elements associated with the salt stress response were present on the promoters of two DsMEs. The deletion of the MYB binding site (MBS) on the DsME2 promoter confirmed that MBS drives the expression of DsME2 to participate in osmotic regulation in D. salina. In conclusion, MEs are the critical enzymes that play pivotal roles in lipid accumulation and osmotic regulation.

16.
Therap Adv Gastroenterol ; 16: 17562848231192144, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37655061

RESUMO

Background: Early fluid resuscitation is one of the main therapeutic strategies for acute pancreatitis (AP). This study investigated the effects of early aggressive and nonaggressive hydration on AP. Objectives: The aim of this meta-analysis is to investigate the differences between aggressive and nonaggressive intravenous fluid resuscitation in AP. Design: This study was based on publicly available data, all of which have been extracted from previous ethically approved studies. Data sources and methods: Two authors systematically searched PubMed, Embase (via OVID), Web of Science, and Cochrane Library to find all published research before February 2023. In-hospital mortality were set as primary endpoints. Results: This meta-analysis included seven randomized controlled trials (RCTs) and eight cohort studies with 4072 individuals in nonaggressive (n = 2419) and aggressive (n = 1653) hydration groups. The results showed that patients in the nonaggressive group had a lower mortality rate than those in the aggressive hydration group [relative risks (RR), 0.66; p = 0.02]. Subgroup analysis results showed that patients in the nonaggressive hydration group had lower mortality rates in RCTs (RR, 0.39; p = 0.001), studies conducted in Eastern countries (RR, 0.63; p = 0.002), and studies with severe pancreatitis (RR, 0.65; p = 0.02). In addition, the nonaggressive hydration group had lower rates of infection (RR, 0.62; p < 0.001), organ failure (RR, 0.65; p = 0.02), and shock (RR, 0.21; p = 0.02), as well as a shorter hospital stay (weighted mean difference, -1.63; p = 0.001) than the aggressive hydration group. Conclusions: Early nonaggressive fluid resuscitation is associated with lower mortality, lower risk of organ failure and infection, and shorter hospital stays than aggressive fluid resuscitation. Registration prospero registration number: CRD42023396388.

17.
Anal Chim Acta ; 1278: 341746, 2023 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-37709475

RESUMO

BACKGROUND: Inductively coupled plasma-mass spectrometry (ICP-MS) is one of the most powerful instrumental techniques for the determination of tungsten for its low detection limit and wide linear range, while it remains challenging since the analytical performance can be affected by complicated sample matrix. Chemical vapor generation (CVG) harbors the potential to be an alternative to conventional solution nebulization for sample introduction to reduce matrix effect. However, the CVG of tungsten was low in efficiency. It is clear that green and homogeneous enhancement for CVG of tungsten is desired and the mechanism is worth in-depth investigation. RESULTS: Two green and homogeneous enhancement systems for CVG of tungsten were studied, including photochemical vapor generation (PVG) and hydride generation (HG) with sensitizers, Fe3+ and DDTC, respectively. Under optimal conditions, the limits of detection (LODs) were 0.02 µg L-1 for the PVG and 0.003 µg L-1 for the HG, respectively. For PVG, the Fe3+/Fe2+ cycling, free radical species, gaseous product, and the chemical speciation evolution of W in the PVG process were studied in detail. Photo-Fenton effect, generated reductive radical ·CO2-, gaseous product Fe(CO)5, and the mixed valence of W5+/W6+ in the PVG process were found to be crucial for the enhancement. As for HG, the complexation between W(VI) and DDTC might be conducive to the enhanced HG efficiency. SIGNIFICANCE: This work not only in-depth expands the element scope of CVG, but also investigates the enhancement mechanisms experimentally, which might render a deep insight into the CVG processes and foreshadow new guidelines for screening green and efficient homogeneous sensitizers for CVGs of more elements in the future.

18.
ACS Appl Mater Interfaces ; 15(30): 36822-36830, 2023 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-37467423

RESUMO

Despite the rapid development of versatile metal-organic frameworks (MOFs), the synthesis of water-stable MOFs remains challenging, which significantly limits their practical applications. Herein, a novel engineering strategy was developed to prepare superhydrophobic MOFs by an in situ fluorinated microporous organic network (FMON) coating. Through controllable modification, the resulting MOF@FMON retained the porosity and crystallinity of the pristine MOFs. Owing to the superhydrophobicity of the FMON and the feasibility of MOF synthesis, the FMON coating could be in situ integrated with various water-sensitive MOFs to provide superhydrophobicity. The coating thickness and hydrophobicity of the MOF@FMON composites were easily regulated by changing the FMON monomer concentration. The MOF@FMON composites exhibited excellent oil/water separation and catalytic activities and enhanced durability in aqueous solutions. This study provides a general approach for the synthesis of superhydrophobic MOFs, expanding the application scope of MOFs.

19.
Adv Healthc Mater ; 12(28): e2301292, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37458333

RESUMO

As a distinctly different way from apoptosis, ferroptosis can cause cell death through excessive accumulation of lipid peroxide (LPO) and show great potential for cancer therapy. However, efficient strategies for ferroptosis therapy are still facing great challenges, mainly due to insufficient endogenous H2 O2 or relatively high pH value for Fenton reaction-dependent ferroptosis, and the high redox level of tumor cells attenuates the oxidation therapy. Herein, an efficient lipid-based delivery system to load oxidation catalyst and glutathione peroxidase 4 (Gpx4) inhibitor is orchestrated, intending to amplify Fenton reaction-independent ferroptosis by bidirectional regulation of LPO accumulation. Ferric ammonium citrate (FAC), Gpx4 inhibitor sorafenib (SF), and unsaturated lipids are constructed into mPEG2K -DSPE-modified liposomes (Lip@SF&FAC). Influenced by the high level of intratumoral glutathione, FAC can be converted into Fe2+ , and subsequently the formed iron redox pair (Fe2+ /Fe3+ ) catalyzes unsaturated phospholipids of liposomes into LPO via a Fenton reaction-independent manner. Meanwhile, SF can downregulate LPO reduction by inhibiting Gpx4 activation. In vitro and in vivo antitumor experiments show that Lip@SF&FAC induces massive LPO accumulation in tumor cells and ultimately exhibits strong tumor-killing ability with negligible side effect. Consequently, this two-pronged approach provides a new ferroptosis strategy for predominant LPO accumulation and enhanced cancer therapy.


Assuntos
Ferroptose , Neoplasias , Humanos , Lipossomos/farmacologia , Oxirredução , Apoptose , Peróxidos Lipídicos , Sorafenibe/farmacologia , Sorafenibe/uso terapêutico , Neoplasias/tratamento farmacológico , Linhagem Celular Tumoral
20.
Cancer Med ; 12(17): 18176-18188, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37519062

RESUMO

BACKGROUND: The health-related quality of life (HRQoL) of patients with localized prostate cancer (LPCa) after treatment mainly surgery and radiotherapy (RT) has received increasing attention. The aim of this study is to compare the HRQoL of LPCa after surgery and RT. METHODS: Web of Science, Embase, PubMed and Cochrane databases were searched after January 2000 to observe the HRQoL scores after surgery and RT at different treatment time points. RESULTS: A total of 28 studies were included in this study, and the results showed that LPCa received surgery had better bowel scores than RT at ≤3 (weighted mean differences [WMD] = 4.18; p = 0.03), 3-6 (WMD = 4.16; p < 0.001), 6-12 (WMD = 2.99; p = 0.004), 24-60 (WMD = 1.87; p = 0.06), and ≥60 (WMD = 4.54; p = 0.02) months. However, LPCa received RT had higher urinary scores at ≤3 (WMD = -7.39; p = 0.02), 3-6 (WMD = -6.03; p = 0.02), 6-12 (WMD = -4.90; p < 0.001), 24-60 (WMD = -3.96; p < 0.001), ≥60 (WMD = -2.95; p < 0.001) months and had better sexual scores at ≤3 (WMD = -13.58; p = 0.09), 3-6 (WMD = -12.32; p = 0.06), 6-12 (WMD = -12.03; p = 0.002), 24-60 (WMD = -11.29; p < 0.001), and ≥60 (WMD = -3.10; p = 0.46) months than surgery. The scores difference between surgery and RT decreased over time. CONCLUSION: Overall, for LPCa, surgery was associated with better HRQoL in the bowel domain, whereas RT was associated with better HRQoL in the urinary and sexual domains, with the difference between surgery and RT narrowing over time.

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