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1.
Transl Cancer Res ; 13(3): 1508-1518, 2024 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-38617508

RESUMO

Background: Programmed cell death protein 1 (PD-1) or its ligand (PD-L1) monoclonal antibody combined with bevacizumab (a monoclonal antibody targeting vascular endothelial growth factor) has been established as first-line systemic treatment for advanced hepatocellular carcinoma (HCC). Radiotherapy is a crucial local treatment for HCC. Mutual efficacy enhancement has been reported between radiotherapy, anti-angiogenesis therapy and immunotherapy in preclinical researches, but not been validated in clinical practice. Whether radiotherapy can enhance efficacy of anti-PD-1 immunotherapy plus bevacizumab for HCC remains unclear. This retrospective observational study aimed to appraise efficacy and safety of the combination of radiotherapy with pembrolizumab (a PD-1 monoclonal antibody) and bevacizumab for advanced HCC for the first time. Methods: Patients with advanced HCC treated by intrahepatic tumor-directed moderately hypo-fractionated radiotherapy combined with pembrolizumab and bevacizumab were consecutively included. Clinicopathological characteristics, therapeutic outcomes and treatment-related adverse events (TRAEs) were recorded and evaluated. Results: A total of 23 patients were eventually enrolled. Median cycles of pembrolizumab and bevacizumab were 4 (median, 1-8) and 4 (median, 1-9) cycles. The objective response rates and disease control rates of irradiated intrahepatic HCC and non-irradiated extrahepatic HCC were 34.8% [95% confidence interval (CI), 16.4-57.3%] vs. 10.0% (95% CI, 1.2-31.7%), and 91.3% (95% CI, 72.0-98.9%) vs. 70.0% (95% CI, 45.7-88.1%), respectively. The median progression-free survival (PFS) and overall survival (OS) were 6.6 (95% CI, 4.7-8.5) and 18.3 (95% CI, 8.2-33.6) months, and 12-month PFS and OS rates were 17.5% (95% CI, 7.0-28.0%) and 60.9% (95% CI, 50.7-71.1%). Two patients (8.7%) with locally advanced, unresectable HCC eventually underwent curative resection of tumors after this trimodal treatment. Eighteen patients (78.3%) had ≥ grade 3 TRAEs, with myelosuppression and transaminase increase as the most common. Conclusions: This study firstly reported that combining radiotherapy with pembrolizumab and bevacizumab was preliminarily a feasible and effective therapeutic choice for advanced HCC in despite of more TRAEs. This tri-modal regimen may be a potential conversion therapy for unresectable, locally advanced HCC. The limitations of this study are its retrospective nature and small sample size; therefore, big-sample prospective studies are warranted to further investigate this tri-modal regimen.

2.
Food Chem ; 449: 139304, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38608611

RESUMO

To evaluate the effect of high voltage pulsed electric field (PEF) treatment (10-20 kV/cm, 5-15 min) on the structural characteristics and sensitization of crude extracts of arginine kinase from Fenneropenaeus chinensis. By simulated in vitro gastric juice digestion (SGF), intestinal juice digestion (SIF) and enzyme-linked immunosorbent assay (ELISA), AK sensitization was reduced by 42.5% when treated for 10 min at an electric field intensity of 15 kV/cm. After PEF treatment, the α-helix content decreased, and the α-helix content gradually changed to ß-sheet and ß-turn. Compared to the untreated group, the surface hydrophobicity increased and the sulfhydryl content decreased. SEM and AFM analyses showed that the treated sample surface formed a dense porous structure and increased roughness. The protein content, dielectric properties, and amino acid content of sample also changed significantly with the changes in the treatment conditions. Non-thermal PEF has potential applications in the development of hypoallergenic foods.

3.
iScience ; 27(4): 109322, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38500828

RESUMO

Lunar-based equipment plays a vital role in the exploration of the moon because it undertakes the tasks of moving, transporting, digging, and so on. In order to control the gait of lunar-based equipment more precisely and guarantee mobile stability, the contact mechanism between its foot and lunar soil is worthy of in-depth study. In this paper, a contact model is proposed to predict the stress, strain, and displacement both on the contact surface and in the lunar soil when the foot is under vertical load. The axial stress in the proposed contact model is verified through the experiment and its accuracy in the lunar equipment is verified through simulation. The error is in a reasonable range and the influence depth of load conforms to the experiment results. This paper provides a relatively accurate model to describe the contact force between the lunar-based equipment's foot and the lunar soil and will promote the research of lunar exploration.

4.
Neurochem Res ; 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38530508

RESUMO

The consumption of a high-fat diet (HFD) has been implicated in the etiology of obesity and various neuropsychiatric disturbances, including anxiety and depression. Compelling evidence suggests that far-infrared ray (FIR) possesses beneficial effects on emotional disorders. However, the efficacy of FIR therapy in addressing HFD-induced anxiety and the underlying mechanisms remain to be elucidated. Here, we postulate that FIR emitted from a graphene-based therapeutic device may mitigate HFD-induced anxiety behaviors. The graphene-FIR modify the gut microbiota in HFD-mice, particularly by an enriched abundance of beneficial bacteria Clostridiaceae and Erysipelotrichaceae, coupled with a diminution of harmful bacteria Lachnospiraceae, Anaerovoracaceae, Holdemania and Marvinbryantia. Graphene-FIR also improved intestinal barrier function, as evidenced by the augmented expression of the tight junction protein occludin and G protein-coupled receptor 43 (GPR43). In serum level, we observed the decreased free fatty acids (FFA), lipopolysaccharides (LPS), diamine oxidase (DAO) and D-lactate, and increased the glucagon-like peptide-2 (GLP-2) levels in graphene-FIR mice. Simultaneously, inflammatory cytokines IL-6, IL-1ß, and TNF-α manifested a decrease subsequent to graphene-FIR treatment in both peripheral and central system. Notably, graphene-FIR inhibited over expression of astrocytes and microglia. We further noticed that the elevated the BDNF and decreased TLR4 and NF-κB expression in graphene-FIR group. Overall, our study reveals that graphene-FIR rescued HFD-induced anxiety via improving the intestine permeability and the integrity of blood-brain barrier, and reduced inflammatory response by down regulating TLR4/NF-κB inflammatory pathway.

5.
Front Oncol ; 14: 1320714, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38487727

RESUMO

Objective: We aimed to investigate the value of contrast-enhanced ultrasound (CEUS) in the preoperative prediction of the histological grades and molecular subtypes of breast cancer. Methods: A total of 183 patients with pathologically confirmed breast cancer were included. Contrast enhancement patterns and quantitative parameters were compared in different groups. The receiver operating characteristic (ROC) curve was used to analyze the efficacy of CEUS in the preoperative prediction of pathological characteristics, including histologic grade and molecular subtypes. Results: Heterogeneous enhancement, perfusion defects, and peripheral radial vessels were mostly observed in higher histologic grade (grade III) breast cancer. Heterogeneous enhancement and perfusion defect were the most effective indicators for grade III breast cancer, with the areas under the ROC curve of 0.768 and 0.756, respectively. There were significant differences in the enhancement intensity, post-enhanced margin, perfusion defects, and peripheral radial vessel among the different molecular subtypes of breast cancer (all P < 0.01). Perfusion defects and clear edge after enhancement were the best qualitative criteria for the diagnosis of HER-2 overexpressed and triple-negative breast cancers, and the corresponding areas under the ROC curves were 0.804 and 0.905, respectively. There were significant differences in PE, WiR, WiPI, and WiWoAUC between grade III vs grade I and II breast cancer (P < 0.05). PE, WiR, WiPI, and WiWoAUC had good efficiency in the diagnosis of high-histologic-grade breast cancer. PE had the highest diagnostic efficiency in Luminal A, while WiPI had the highest diagnostic efficiency in Luminal B subtype breast cancer, and the areas under the ROC curve were 0.825 and 0.838, respectively. WiWoAUC and WiR were the most accurate parameters for assessing triple-negative subtype breast cancers, and the areas under the curve were 0.932 and 0.922, respectively. Conclusion: Qualitative and quantitative perfusion analysis of contrast-enhanced ultrasound may be useful in the non-invasive prediction of the histological grade and molecular subtypes of breast cancers.

6.
Food Chem ; 447: 139006, 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-38492305

RESUMO

Pancreatic lipase (PL) and cholesterol esterase (CE) are vital digestive enzymes that regulate lipid digestion. Three bioactive peptides (LFCMH, RIPAGSPF, YFRPR), possessing enzyme inhibitory activities, were identified in the seed proteins of R. roxburghii. It is hypothesized that these peptides could inhibit the activities of these enzymes by binding to their active sites or altering their conformation. The results showed that LFCMH exhibited superior inhibitory activity against these enzymes compared to the other peptides. The inhibition mechanisms of the three peptides were identified as either competitive or mixed, according to inhibition models. Further studies have shown that peptides could bind to the active sites of enzymes, thus affecting their spatial conformation and restricting substrate entry into the active site. Molecular simulation further proved that hydrogen bonds and hydrophobic interactions played a vital role in the binding of peptides to enzymes. This study enriches our understanding of interaction mechanisms of peptides on PL and CE.


Assuntos
Inibidores Enzimáticos , Esterol Esterase , Inibidores Enzimáticos/farmacologia , Lipase/química , Peptídeos/farmacologia , Termodinâmica
7.
J Food Sci ; 89(4): 2450-2464, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38462851

RESUMO

Fermented foods have shown promise in preventing or treating ulcerative colitis (UC) via regulating intestinal flora and correcting metabolic disorders. However, the prevention effect of fermented Wallace melon juice (FMJ) on UC is unclear. In this study, the effects of FMJ on dextran sodium sulfate (DSS)-induced UC were investigated via 16S rRNA sequencing and non-targeted metabolomics. The results showed that FMJ was effective in alleviating the symptoms of UC, reducing histological damage and oxidative stress, decreasing the levels of pro-inflammatory cytokines. After FMJ treatment, the level of propionic acid, butyric acid, and valeric acid increased by 14.1%, 44.4%, and 52.4% compared to DSS-induced UC mice. Meanwhile, the levels of harmful bacteria such as Oscillospira, Bacteroidetes, and Erysipelotrichaceae and Clostridium decreased, while the levels of beneficial bacteria such as Akkermansia, Lactobacillus, and Bifidobacterium increased. Fecal metabolomics analysis identified 31 differential metabolites, which could regulate metabolic disorders in UC mice by controlling the primary bile acid biosynthesis, purine metabolism, and pantothenate and CoA biosynthesis pathway. Additionally, the abundances of butyric acid, bile acids, and pantothenic acid were positively correlated with Allobaculum, Bifidobacterium, and other beneficial bacteria (R2 > 0.80, p < 0.01). The results indicated that FMJ played a role in regulating the structure of intestinal flora, which in turn helped in repairing metabolic disorders and alleviated colitis inflammation.


Assuntos
Colite Ulcerativa , Colite , Microbioma Gastrointestinal , Doenças Metabólicas , Animais , Camundongos , Lactobacillus , Colite Ulcerativa/induzido quimicamente , Sulfato de Dextrana/efeitos adversos , RNA Ribossômico 16S , Ácido Butírico , Bifidobacterium , Firmicutes , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças , Colo
8.
Fitoterapia ; 174: 105880, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38431026

RESUMO

An undescribed trichodenone derivative (1), two new diketopiperazines (3 and 4) along with a bisabolane analog (2) were isolated from Trichoderma hamatum b-3. The structures of the new findings were established through comprehensive analyses of spectral evidences in HRESIMS, 1D and 2D NMR, Marfey's analysis as well as comparisons of ECD. The absolute configuration of 2 was unambiguously confirmed by NMR, ECD calculation and Mo2(AcO)4 induced circular dichroism. Compounds 1-4 were tested for their fungicidal effects against eight crop pathogenic fungi, among which 1 showed 51% inhibition against Sclerotinia sclerotiorum at a concentration of 50 µg/mL.


Assuntos
Hypocreales , Trichoderma , Estrutura Molecular , Dicetopiperazinas/química , Trichoderma/química
9.
Am J Transl Res ; 16(2): 681-689, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38463597

RESUMO

Novel coronavirus pneumonia, also known as coronavirus disease 2019 (COVID-19), is caused by sub-severe acute respiratory syndrome type 2 coronavirus (SARS-CoV-2) infection. The spike (S) protein of SARS-CoV-2 binds to angiotensin-converting enzyme 2 (ACE2) receptors widely expressed on the surface of human cells leading to life-threatening respiratory infections. A serious hazard to human health is posed by the lack of particular treatment medications for this virus infection. We advocate the creation of high-affinity antibodies using the receptor binding domain (RBD) of S protein as a specific antigenic epitope to develop a drug that can precisely target therapy COVID-19 because SARS-CoV-2 infection of the host cells is dependent on S protein binding to ACE2. Finally, we obtained high-affinity antibodies 14F4HL and 14E3HL that have high affinity with RBD and well-drug-forming properties, suitable for further humanization studies. Thus, monoclonal antibodies that neutralize the S protein were identified in our study, which may provide new insights for the development of COVID-19 therapeutic drugs.

10.
Front Immunol ; 15: 1355128, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38361942

RESUMO

Background: Living donor (LD) kidney transplantation in the setting of ABO blood group incompatibility (ABOi) has been previously reported to be associated with increased risk for antibody-mediated rejection (ABMR). It is however unclear if the presence of pre-transplant donor specific antibodies (DSA) works as an additive risk factor in the setting of ABOi and if DSA positive ABOi transplants have a significantly worse long-term outcome as compared with ABO compatible (ABOc) DSA positive transplants. Methods: We investigated the effect of pre-transplant DSA in the ABOi and ABOc setting on the risk of antibody-mediated rejection (ABMR) and graft loss in a cohort of 952 LD kidney transplants. Results: We found a higher incidence of ABMR in ABOi transplants as compared to ABOc transplants but this did not significantly affect graft survival or overall survival which was similar in both groups. The presence of pre-transplant DSA was associated with a significantly increased risk of ABMR and graft loss both in the ABOi and ABOc setting. We could not detect an additional risk of DSA in the ABOi setting and outcomes were comparable between DSA positive ABOi and ABOc recipients. Furthermore, a combination of DSA directed at both Class I and Class II, as well as DSA with a high mean fluorescence intensity (MFI) showed the strongest relation to ABMR development and graft loss. Conclusion: The presence of pre-transplant DSA was associated with a significantly worse long-term outcome in both ABOi and ABOc LD kidney transplants and our results suggests that the risk associated with pre-transplant DSA is perhaps not augmented in the ABOi setting. Our study is the first to investigate the long-term effects of DSA in the ABOi setting and argues that pre-transplant DSA risk could potentially be evaluated similarly regardless of ABO compatibility status.


Assuntos
Transplante de Rim , Humanos , Transplante de Rim/efeitos adversos , Estudos de Coortes , Suíça/epidemiologia , Doadores Vivos , Rejeição de Enxerto , Sistema ABO de Grupos Sanguíneos , Anticorpos
11.
Nutrients ; 16(4)2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38398871

RESUMO

Although previous studies have shown significant associations between individual lifestyles and metabolic syndrome, limited studies have explored the combined effect of lifestyles. The purpose of this study was to investigate whether a combined lifestyle score was associated with metabolic syndrome incidence in Hong Kong Chinese women. This prospective cohort study included 1634 women (55.9 ± 8.6 years) without baseline metabolic syndrome, diabetes, myocardial infarction, or stroke. Eight lifestyle factors (smoking, physical activity, sedentary time, sleep, stress, fatigue, diet, and alcohol) were included by assigning 0 (unhealthy) or 1 point (healthy). The overall score was the sum of these points, ranging from 0 (the least healthy) to 8 points (the healthiest). Metabolic syndrome was diagnosed by the joint interim statement. During a 1.16-year follow-up, 179 (11.0%) new metabolic syndrome cases were identified. The incidences for the 0-3-point, 4-point, 5-point, and 6-8-point groups were 12.8% (79/618), 11.5% (42/366), 9.4% (29/309), and 8.5% (29/341), respectively. Compared to the lowest combined lifestyle score group, the highest group had a 47% reduced metabolic syndrome incidence, with an adjusted odds ratio and 95% confidence interval of 0.53 (0.33-0.86) (p = 0.010). These findings indicate that a higher combined lifestyle score was associated with a lower metabolic syndrome incidence in this population.


Assuntos
Síndrome Metabólica , Humanos , Feminino , Síndrome Metabólica/epidemiologia , Fatores de Risco , Estudos Prospectivos , Consumo de Bebidas Alcoólicas/epidemiologia , Estilo de Vida , Estilo de Vida Saudável , Incidência
12.
Pharmaceuticals (Basel) ; 17(2)2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38399440

RESUMO

Triple-negative breast cancer (TNBC) poses a therapeutic challenge due to its aggressive nature and lack of targeted therapies. Epigenetic modifications contribute to TNBC tumorigenesis and drug resistance, offering potential therapeutic targets. Recent advancements in three-dimensional (3D) organoid cultures, enabling precise drug screening, hold immense promise for identifying novel compounds targeting TNBC. In this study, we established two patient-derived TNBC organoids and implemented a high-throughput drug screening system using these organoids and two TNBC cell lines. Screening a library of 169 epigenetic compounds, we found that organoid-based systems offer remarkable precision in drug response assessment compared to cell-based models. The top 30 compounds showing the highest drug sensitivity in the initial screening were further assessed in a secondary screen. Four compounds, panobinostat, pacritinib, TAK-901, and JIB-04, targeting histone deacetylase, JAK/STAT, histone demethylases, and aurora kinase pathways, respectively, exhibited potent anti-tumor activity in TNBC organoids, surpassing the effect of paclitaxel. Our study highlights the potential of these novel epigenetic drugs as effective therapeutic agents for TNBC and demonstrates the valuable role of patient-derived organoids in advancing drug discovery.

13.
Anatol J Cardiol ; 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38372344

RESUMO

Myocardial ischemia/reperfusion injury (MIRI) is a pathophysiological process connected to the onset of numerous heart disorders. The pathogenesis of MIRI is complex, and it mainly involves calcium overload, classic oxidative stress, mitochondrial disorder, inflammation, microvascular disorder, and cell death. The clinical treatment options for MIRI are presently constrained, making it imperative to develop new treatment modalities. Recent studies have demonstrated that ferroptosis is the main cause of MIRI. Ferroptosis is a new type of regulated iron-dependent cell death whose mechanism and targeted therapy are anticipated to be novel therapeutic techniques for MIRI. Herein, the primary mechanism underlying ferroptosis (the 3 major metabolic routes involving iron, amino acids, and lipids, and in MIRI, the specific mechanism and therapeutic target of ferroptosis) are discussed to determine the potential therapeutic approach for MIRI.

14.
Eur J Med Chem ; 267: 116183, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38354520

RESUMO

Triggering ferroptosis is a potential therapeutic pathway and strategy for the prospective treatment of lethal hepatocellular carcinoma (HCC). The asialo-glycoprotein receptor (ASGPR) is an over-expressed receptor on the membranes of hepatocellular carcinoma cells (HCCs) and binds specifically to galactose (Gal) ligand. Celastrol (CE) is a potent anticancer natural product, but its poor water solubility and severe toxicity restrict its clinical application. In this study, a carrier-free self-assembled nanoparticles, CE-Gal-NPs, were designed and prepared by nanoprecipitation method, which could recognize ASGPR receptor by active targeting (Gal ligand) and passive targeting (EPR effect), access to the cell through the clathrin pathway and finally internalize to lysosomes. CE-Gal-NPs triggered reactive oxygen species (ROS)-mediated ferroptosis pathway and exerted anti-HCC effects in vitro and in vivo by down-regulating GPX4 and up-regulating COX-2 expression, depleting glutathione (GSH) levels, and increasing lipid peroxidation levels in cells and tumor tissues. In the H22 xenograft mouse model, the CE-Gal-NPs group exhibited dramatically superior tumor inhibition than the CE group, while Gal conjugating diminished the systemic toxicity of CE. Consequently, this study presented a promising strategy for CE potentiation and toxicity reduction, as well as a potential guideline for the development of clinically targeted therapeutic agents for HCC.


Assuntos
Carcinoma Hepatocelular , Ferroptose , Neoplasias Hepáticas , Triterpenos Pentacíclicos , Humanos , Camundongos , Animais , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Galactose , Nanomedicina , Ligantes , Células Hep G2
15.
Theor Appl Genet ; 137(3): 51, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38369666

RESUMO

KEY MESSAGE: ClLOX, is located on chromosome 2 and encodes a lipoxygenase gene, which induced watermelon powdery mildew resistance by inhibiting pathogen spread. Powdery mildew is one of the most severe fungal diseases reducing yield and quality of watermelon (Citrullus lanatus L.) and other cucurbit crops. Genes responsible for powdery mildew resistance in watermelon are highly valuable. In this study, we first identified the QTL pm-lox for powdery mildew resistance in watermelon, located within a 0.93 Mb interval of chromosome 2, via XP-GWAS method using two F2 populations. The F2:3 families from one of the F2 populations were then used for fine-mapping the pm-lox locus into a 9,883 bp physical region between 29,581,906 and 29,591,789, containing only two annotated genes. Of these, only ClG42_02g0161300 showed a significant differential expression between the resistant and susceptible lines after powdery mildew inoculation based on RNA sequencing (RNA-seq) and qRT-PCR analysis, and is designated ClLOX. Derived Cleaved Amplified Polymorphic Sequence (dCAPs) markers were developed and validated. In addition, our tests showed that the resistance was anti-spread rather than anti-infection of the pathogen. This study identified a new resistance gene (ClLOX), provided insights into the mechanism of powdery mildew resistance, and developed a molecular marker for watermelon breeding.


Assuntos
Ascomicetos , Citrullus , Humanos , Mapeamento Cromossômico/métodos , Resistência à Doença/genética , Citrullus/genética , Citrullus/microbiologia , Ascomicetos/genética , Melhoramento Vegetal , Doenças das Plantas/genética , Doenças das Plantas/microbiologia
16.
Adv Sci (Weinh) ; 11(13): e2307793, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38240362

RESUMO

Low-carbon alkaline thermal hydrolysis of sewage sludge for the production of high-quality plant-growth-promoting nutrients and biostimulants is a growing concern for sludge resource utilization in agriculture. Thus, this study aims to investigate functional characteristics and soil biochemical effects of sewage sludge-derived nutrients and biostimulants (SS-NB). The content of heavy metals in SS-NB decreased by 47.39-100%, and an increase in soil protease, invertase, and soil nutrient utilization rates are observed in SS-NB groups. SS-NB substituted for chemical fertilizer increased the diversity and evenness of microbial community and reduced the abundance of the soil-borne bacterial genus Arthrobacter. The dominant community of SS-NB100 group is mainly enriched in Microvirga, Ensifer, Novosphingobium, Bosea and Ellin6055, which are principally beneficial symbiotic bacteria of plants and participated in C and N cycles. Moreover, SS-NB reduced the accumulation of Ktedonobacteria and Nitrosospira, which are involved in the production of CO2 and N2O, and also enhanced the coordination of soil microorganisms with enzyme activities and nutrient utilization rate. In conclusion, the results suggest that SS-NB exerts a positive effect on reducing greenhouse gas emissions and preventing soil-borne diseases, and can further enhance collaboration with soil enzyme activity and soil nutrient utilization by stimulating soil microorganisms.


Assuntos
Esgotos , Solo , Solo/química , Esgotos/química , Hidrólise , Agricultura , Nutrientes
17.
Artigo em Inglês | MEDLINE | ID: mdl-38204247

RESUMO

BACKGROUND: Silybin, a major flavonoid extracted from the seeds of milk thistle, has a strong hepatoprotective but weak anti-hepatoma activity. Screening another natural ingredient and combining it with silybin is expected to improve the anti-hepatoma efficacy of silybin. OBJECTIVE: The objective of this study was to investigate the synergistic anti-hepatoma effect of resveratrol and silybin on HepG2 cells and H22 tumor-bearing mice in hepatocellular carcinoma (HCC) in vitro and in vivo, respectively. METHODS: Cell viability, scratch wound, clone formation, cell apoptosis, cell cycle, and western blot analysis of HepG2 cells were used to investigate the synergistic effects in vitro of the combination resveratrol with silybin. Growth rates, tumor weights, organ indexes, and histological pathological examination in H22 tumor-bearing mice were used to investigate the synergistic effects in vivo. RESULTS: The combination of resveratrol (50 µg/mL) and silybin (100 µg/mL) significantly suppressed cell viability, whose combination index (CI) was 1.63 (>1.15), indicating the best synergism. The combination exhibited the synergistic effect in blocking the migration and proliferative capacity of HepG2 cells in the measurement in vitro. In particular, resveratrol enhanced the upregulation of Bcl-2 expression and the downregulation of Bax expression with a concurrent increase in the Bax/Bcl-2 ratio. The combination of resveratrol (50 mg/kg) and silybin (100 mg/kg) reduced the tumor weight, inhibited the growth rate, increased the organ indexes, and destroyed the tumor tissue morphology in H22 tumor-bearing mice. CONCLUSION: Resveratrol was found to exhibit synergistic anti-cancer effects with silybin on HepG2 cells and H22 tumor-bearing mice.

18.
Analyst ; 149(3): 859-869, 2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38167646

RESUMO

High efficiency, stability, long emission wavelength (NIR-II), and good biocompatibility are crucial for photosensitizers in phototherapy. However, current Food and Drug Administration (FDA)-approved organic fluorophores exhibit poor chemical stability and photostability as well as short emission wavelength, limiting their clinical usage. To address this, we developed Se-IR1100, a novel organic photosensitizer with a photostable and thermostable benzobisthiadiazole (BBTD) backbone. By incorporating selenium as a heavy atom and constructing a D-A-D structure, Se-IR1100 exhibits a maximum fluorescence emission wavelength of 1100 nm. Compared with FDA-approved indocyanine green (ICG), DSPE-PEGylated Se-IR1100 nanoparticles exhibit prominent photostability and long-lasting photothermal effects. Upon 808 nm laser irradiation, Se-IR1100 NPs efficiently convert light energy into heat and reactive oxygen species (ROS), inducing cancer cell death in cellular studies and living organisms while maintaining biocompatibility. With salient photostability and a photothermal conversion rate of 55.37%, Se-IR1100 NPs hold promise as a superior photosensitizer for diagnostic and therapeutic agents in oncology. Overall, we have designed and optimized a multifunctional photosensitizer Se-IR1100 with good biocompatibility that performs NIR-II fluorescence imaging and phototherapy. This dual-strategy method may offer novel approaches for the development of multifunctional probes using dual-strategy or even multi-strategy methods in bioimaging, disease diagnosis, and therapy.


Assuntos
Nanopartículas , Neoplasias , Selênio , Humanos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química , Fototerapia/métodos , Verde de Indocianina/toxicidade , Nanopartículas/química , Neoplasias/tratamento farmacológico , Linhagem Celular Tumoral
19.
J Sci Food Agric ; 104(6): 3776-3787, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38294418

RESUMO

BACKGROUND: Melons (Cucumis melo L.) are among the most commonly consumed fruits but they are highly susceptible to mechanical damage and rot during storage and transportation. New processed products are needed to avoid postharvest fruit loss and to increase health benefits. Fermentation is an effective means of utilizing the nutrients and improving flavor. RESULTS: Fermented melon juice (MJ) was prepared using three potential probiotics Lactiplantibacillus plantarum CICC21824 (LP), Lactiplantibacillus plantarum GB3-2 (LG), and Lactiplantibacillus pentosus XZ-34 (LX). The nutrition, flavor characteristics, and digestive properties of different fermented MJs were compared. The results demonstrated that, in comparison with mono-fermentation, mixed fermentation by LG and LX could increase the level of organic acids and phenolic acids. Correspondingly, antioxidant capacity was improved significantly and positively correlated with p-coumaric acid and cinnamic acid content. The production of alcohols and acids was more strongly enhanced by mixed culture fermentation, whereas mono-fermentation reduced the content of esters, especially ethyl acetate and isopropyl acetate. Aldehydes and ketones increased significantly in fermented MJ, and damascenone and heptanal could be the characteristic aroma compounds. CONCLUSION: Mixed fermented MJ provides more beneficial phytochemicals, better flavor, and stronger antioxidant properties than mono-fermentation. © 2024 Society of Chemical Industry.


Assuntos
Antioxidantes , Cucurbitaceae , Fermentação , Antioxidantes/química , Cucurbitaceae/metabolismo , Frutas/química , Álcoois/análise
20.
Int J Biol Macromol ; 254(Pt 1): 127419, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37848115

RESUMO

In this study, chitosan coatings with different degrees of deacetylation (DD, 88.1 % and 95.2 %) were electrostatically sprayed on sweet cherries to evaluate their impacts on postharvest characteristics and internal metabolism. The results showed that chitosan coating could effectively delay the change of weight, color, firmness, and maintain the content of total phenols, flavonoids and titratable acids, and inhibit the activities of ß-galactosidase and polyphenol oxidase during cold storage. The storage qualities and physiological activities of sweet cherry were significantly correlated with the contents of sorbitol, 4-hydroxycinnamic acid, hydrogenated hydroxycinnamic acid, tyrosine, proline, glutamine, phenylalanine, and other metabolites. Chitosan coating may modulate fruit quality by inhibiting the energy metabolism, accelerating the accumulation of carbohydrates, and promoting the metabolism of phenylalanine and flavonoid. Especially, chitosan coating with 88.1 % DD had better wettability on sweet cherry's peel and displayed more obvious preservation effect through stronger metabolic regulation ability.


Assuntos
Quitosana , Prunus avium , Conservação de Alimentos/métodos , Quitosana/farmacologia , Frutas , Flavonoides/metabolismo , Fenilalanina/metabolismo
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