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1.
J Pharm Anal ; 14(3): 401-415, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38618249

RESUMO

Activation of nuclear factor erythroid 2-related factor 2 (Nrf2) by Kelch-like ECH-associated protein 1 (Keap1) alkylation plays a central role in anti-inflammatory therapy. However, activators of Nrf2 through alkylation of Keap1-Kelch domain have not been identified. Deoxynyboquinone (DNQ) is a natural small molecule discovered from marine actinomycetes. The current study was designed to investigate the anti-inflammatory effects and molecular mechanisms of DNQ via alkylation of Keap1. DNQ exhibited significant anti-inflammatory properties both in vitro and in vivo. The pharmacophore responsible for the anti-inflammatory properties of DNQ was determined to be the α, ß-unsaturated amides moieties by a chemical reaction between DNQ and N-acetylcysteine. DNQ exerted anti-inflammatory effects through activation of Nrf2/ARE pathway. Keap1 was demonstrated to be the direct target of DNQ and bound with DNQ through conjugate addition reaction involving alkylation. The specific alkylation site of DNQ on Keap1 for Nrf2 activation was elucidated with a synthesized probe in conjunction with liquid chromatography-tandem mass spectrometry. DNQ triggered the ubiquitination and subsequent degradation of Keap1 by alkylation of the cysteine residue 489 (Cys489) on Keap1-Kelch domain, ultimately enabling the activation of Nrf2. Our findings revealed that DNQ exhibited potent anti-inflammatory capacity through α, ß-unsaturated amides moieties active group which specifically activated Nrf2 signal pathway via alkylation/ubiquitination of Keap1-Kelch domain, suggesting the potential values of targeting Cys489 on Keap1-Kelch domain by DNQ-like small molecules in inflammatory therapies.

2.
Fitoterapia ; : 105967, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38631597

RESUMO

Sulfur-containing natural products possess a variety of biological functions including antitumor, antibacterial, anti-inflammatory and antiviral activities. In this study, four previously undescribed sulfur-containing compounds asperteretals L and M, terreins A and B, together with 17 known compounds were obtained from a culture of marine fungus A. terreus supplemented with inorganic sulfur source Na2SO4. Their planar structures and absolute configurations were elucidated by NMR, HRESIMS, and ECD experiments. The in vitro cytotoxicities of compounds 1-21 against HCT-116 and Caco-2 were evaluated by SRB assay. Asperteretal M (2) exhibited activity against HCT-116 with the IC50 value at 30 µM. The antiproliferative effect of asperteretal M was confirmed by colony formation assay and cell death staining. Furthermore, the preliminary study on the anti-colon cancer mechanism of asperteretal M was performed by RNA-seq analysis. Western blotting validated that asperteretal M significantly decreased the expression of cell-cycle regulatory proteins CDK1, CDK4, and PCNA in a concentration-dependent manner.

3.
Heliyon ; 10(7): e27928, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38560266

RESUMO

Objective: Papillary thyroid carcinoma (PTC) accounts for the majority of thyroid cancers and has a high recurrence rate. We aimed to screen key genes involved in PTC to provide novel insights into the mechanisms of PTC. Methods: Seven microarray datasets of PTC were downloaded from gene expression omnibus database. Differentially expressed genes (DEGs) between PTC and normal samples were screened in the merged dataset. Then, protein-protein interaction (PPIs) functional modules analysis and weighted gene co-expression network analysis (WGCNA) were utilized to identify PTC-associated key genes. The identified key genes were then characterized from various aspects, including gene set enrichment analysis (GSEA) and the associations with immune infiltration, methylation levels and prognosis. Results: A large numbers of DEGs were identified, and these DEGs are involved in several cancer pathways. Nine key genes (including down-regulated genes GNA14, AVPR1A, and WFS1, and up-regulated genes LAMB3, PLAU, MET, MFGE8, PRSS23, and SERPINA1) were identified. Patients in the AVPR1A and GNA14 high expression groups had better disease-free survival (DFS) than those in the low expression group. Key genes were mainly involved in P53 pathway, estrogen response, apoptosis, glycolysis, NOTCH signaling, epithelial mesenchymal transition, WNT_beta catenin signaling, and inflammatory response. The expression of key genes was associated with immune cell infiltration and corresponding methylation levels. The verification results of key gene proteins and mRNA expression levels using external validation datasets were consistent with our expectations, implying the involvements of key genes in PTC. Conclusion: The key genes may serve as potential therapeutic targets for PTC. This study provides novel insights into the mechanisms underlying PTC development.

4.
Ann Med ; 56(1): 2337738, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38590185

RESUMO

BACKGROUND: Early antimicrobial therapy is crucial regarding the prognosis of vertebral osteomyelitis, but early pathogen diagnosis remains challenging. OBJECTIVE: In this study, we aimed to differentiate the types of pathogens in iatrogenic vertebral osteomyelitis (IVO) and native vertebral osteomyelitis (NVO) to guide early antibiotic treatment. METHODS: A total of 145 patients, who had confirmed spinal infection and underwent metagenomic next-generation sequencing (mNGS) testing, were included, with 114 in the NVO group and 31 in the IVO group. Using mNGS, we detected and classified 53 pathogens in the 31 patients in the IVO group and 169 pathogens in the 114 patients in the NVO group. To further distinguish IVO from NVO, we employed machine learning algorithms to select serum biomarkers and developed a nomogram model. RESULTS: The results revealed that the proportion of the Actinobacteria phylum in the NVO group was approximately 28.40%, which was significantly higher than the 15.09% in the IVO group. Conversely, the proportion of the Firmicutes phylum (39.62%) in the IVO group was markedly increased compared to the 21.30% in the NVO group. Further genus-level classification demonstrated that Staphylococcus was the most common pathogen in the IVO group, whereas Mycobacterium was predominant in the NVO group. Through LASSO regression and random forest algorithms, we identified 5 serum biomarkers including percentage of basophils (BASO%), percentage of monocytes (Mono%), platelet volume (PCT), globulin (G), activated partial thromboplastin time (APTT) for distinguishing IVO from NVO. Based on these biomarkers, we established a nomogram model capable of accurately discriminating between the two conditions. CONCLUSION: The results of this study hold promise in providing valuable guidance to clinical practitioners for the differential diagnosis and early antimicrobial treatment of vertebral osteomyelitis.


Assuntos
Anti-Infecciosos , Osteomielite , Humanos , Sequenciamento de Nucleotídeos em Larga Escala , Osteomielite/diagnóstico , Osteomielite/tratamento farmacológico , Biomarcadores , Doença Iatrogênica , China/epidemiologia , Sensibilidade e Especificidade
5.
Org Lett ; 26(15): 3119-3123, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38588021

RESUMO

Six oxidosqualene cyclases (NiOSC1-NiOSC6) from Neoalsomitra integrifoliola were characterized for the biosynthesis of diverse triterpene scaffolds, including tetracyclic and pentacyclic triterpenes from the 2,3-oxidosqualene (1) and oxacyclic triterpenes from the 2,3:22,23-dioxidosqualene (2). NiOSC1 showed high efficiency in the production of naturally rare (20R)-epimers of oxacyclic triterpenes. Mutagenesis results revealed that the NiOSC1-F731G mutant significantly increased the yields of (20R)-epimers compared to the wild type. Homology modeling and molecular docking elucidated the origin of the (20R)-configuration in the epoxide addition step.


Assuntos
Transferases Intramoleculares , Esqualeno/análogos & derivados , Triterpenos , Simulação de Acoplamento Molecular , Triterpenos Pentacíclicos , Transferases Intramoleculares/genética
6.
Medicine (Baltimore) ; 103(15): e37411, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38608087

RESUMO

BACKGROUND: Colonoscopy is a commonly performed gastroenterological procedure in patients associated with anxiety and pain. Various approaches have been used to provide sedation and analgesia during colonoscopy, including patient-controlled analgesia and sedation (PCAS). This study aims to evaluate the feasibility and efficiency of PCAS administered with propofol and remifentanil for colonoscopy. METHODS: This randomized controlled trial was performed in an authorized and approved endoscopy center. A total of 80 outpatients were recruited for the colonoscopy studies. Patients were randomly allocated into PCAS and total intravenous anesthesia (TIVA) groups. In the PCAS group, the dose of 0.1 ml/kg/min of the mixture was injected after an initial bolus of 3 ml mixture (1 ml containing 3 mg of propofol and 10 µg of remifentanil). Each 1 ml of bolus was delivered with a lockout time of 1 min. In the TIVA group, patients were administered fentanyl 1 µg/kg, midazolam 0.02 mg/kg, and propofol (dosage titrated). Cardiorespiratory parameters and auditory evoked response index were continuously monitored during the procedure. The recovery from anesthesia was assessed using the Aldrete scale and the Observer's Assessment of Alertness/Sedation Scale. The Visual Analogue Scale was used to assess the satisfaction of patients and endoscopists. RESULTS: No statistical differences were observed in the Visual Analogue Scale scores of the patients (9.58 vs 9.50) and the endoscopist (9.43 vs 9.30). A significant decline in the mean arterial blood pressure, heart rate, and auditory evoked response index parameters was recorded in the TIVA group (P < 0.05). The recovery time was significantly shorter in the PCAS group than in the TIVA group (P = 0.00). CONCLUSION: The combination of remifentanil and propofol could provide sufficient analgesia, better hemodynamic stability, lighter sedation, and faster recovery in the PCAS group of patients compared with the TIVA group.


Assuntos
Agnosia , Propofol , Humanos , Remifentanil , Midazolam , Analgesia Controlada pelo Paciente , Fentanila , Anestesia Intravenosa , Anestesia Geral , Colonoscopia , Dor
7.
J Phys Chem Lett ; 15(14): 3828-3834, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38557063

RESUMO

Ultrawide bandgap semiconductor ß-Ga2O3 (4.9 eV), with its monoclinic crystal structure, exhibits distinct anisotropic characteristics both optically and electrically, making it an ideal material for solar-blind polarization photodetectors. In this work, ß-Ga2O3 epitaxial films were deposited on sapphire substrates with different orientations, and the mechanisms underlying the anisotropy of these epitaxial films were investigated. Compared to c-plane sapphire, the lattice mismatch between m- or r-plane sapphire and ß-Ga2O3 is more pronounced, disrupting the rotational symmetry of the films and rendering them anisotropic. Thanks to the improved anisotropy, the polarization ratio of the photodetector based on ß-Ga2O3 films grown on r-plane substrates is 0.24, nearly ten times higher than that on c-plane substrates. Finally, by utilizing these polarization-sensitive photodetectors, we developed an encrypted solar-blind ultraviolet optical communication system. Our work provides a new approach to facilitate the fabrication and application of high-performance polarization-sensitive solar-blind photodetectors.

8.
Infect Drug Resist ; 17: 1523-1528, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38645888

RESUMO

Background: Nocardiosis is primarily an opportunistic infection affecting immunocompromised individuals, with a predilection for the lungs, brain, or skin in those with compromised immune function. Granulomatous hepatitis caused by Nocardia is a rare clinical manifestation. This study aims to provide a systematic overview of the clinical features of Nocardiosis caused by Nocardia farcinica, enhancing our understanding of this disease. Methods: We report a case of a 75-year-old male with no underlying diseases presenting with a history of "recurrent fever for more than 4 months", along with fatigue, poor appetite, and pleural and abdominal effusion. Despite treatment at multiple hospitals, the patient showed little improvement. Chest CT revealed chronic inflammation, small nodules, bilateral pleural effusion, and pleural thickening. Abdominal CT indicated multiple low-density lesions in the liver, multiple small calcifications, and abdominal effusion. Results: Liver biopsy suggested inflammatory changes, with focal granuloma formation. Metagenomic next-generation sequencing (mNGS) of liver tissue indicated Nocardia farcinica, leading to the final diagnosis of disseminated Nocardia farcinica granulomatous hepatitis. Conclusion: Nocardia infection is a rare disease primarily observed in immunocompromised patients but can also occur in those with normal immune function. The clinical and radiological features lack specificity; however, the utilization of mNGS technology enables rapid identification of the pathogenic microorganism. Nocardia farcinica is generally susceptible to sulfonamide drugs and amikacin, offering viable treatment options.

9.
Opt Lett ; 49(6): 1575-1578, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38489454

RESUMO

Spatiotemporal mode-locked (STML) fiber lasers have become a new platform for investigating nonlinear phenomena. In this work, spatiotemporal dual-periodic soliton pulsation (SDSP) is firstly observed in an STML fiber laser. It is found that in the SDSP, the long-period pulsations (LPPs) of different transverse modes are synchronous, while the short-period pulsations (SPPs) exhibit asynchronous modulations. The numerical simulation confirms the experimental results and further reveals that the proportion of transverse mode components can manipulate the periods of the LPP and SPP but does not affect the synchronous and asynchronous pulsations of different transverse modes. The obtained results bring the study of spatiotemporal dissipative soliton pulsation into the multi-period modulation stage, which helps to understand the complex spatiotemporal dynamics in STML fiber lasers and discover new dynamics in high-dimensional nonlinear systems.

10.
Foods ; 13(5)2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38472878

RESUMO

In order to improve the retrogradation of rice starch (RS) and the quality of rice products, soy protein isolate (SPI), whey protein isolate (WPI), and rice flour were mixed and further extruded into mixed flour. The physicochemical properties and morphology of starch of extruded rice flour (ERS) and starch of extruded mixtures of SPI, WPI, and rice flour (SPI-WPI-ERS) were analyzed. The distribution of amylopectin chain length, molecular weight, microstructure, crystallinity, short-range ordered structure, pasting properties, and thermodynamic properties of RS, ERS, and SPI-WPI-ERS were measured. The results showed that, compared with rice starch, the proportion of long-chain starch, total starch content, and molecular weight were decreased in ERS and SPI-WPI-ERS, but the proportion of short-chain and amylose content was increased. The short-range order structure was destroyed. The water absorption of ERS and SPI-WPI-ERS was much higher than rice starch at 55 °C, 65 °C, and 75 °C, but lower than that of rice starch at 95 °C. Therefore, the retrogradation characteristics of SPI-WPI-ERS were improved. The setback of rice starch products was reduced and the setback of SPI-WPI-ERS was lower than that of ERS. Overall, the retrogradation of rice starch was delayed by adding exogenous protein and extrusion technology, and the application range of rice flour in staple food products was broadened.

11.
Biol Trace Elem Res ; 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38472512

RESUMO

Minerals are the essential micronutrients for human health. Brown rice is a whole-grain food rich in minerals, with its bran portion limiting the application of minerals. In the present study, the changes in the contents of 23 different minerals (Na, Mg, K, Ca, B, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Se, Sb, Ba, Li, Al, As, Cd, Sn, Hg, and Pb) in brown rice were evaluated during 17, 24, 30, 35, and 48 h of germination. The results showed that germination was associated with the decreased contents of Pb, Cd, As, Al, Li, Ba, Fe, Cr, Co, V, and Hg, and the increased content of Na in brown rice (p < 0.05). In contrast, this process was not significantly influential on the contents of Mg, K, Ca, B, Ni, Cu, Zn, Se, Sn, Sb, and Mn (p > 0.05). In addition, significant correlations were found among most of the mineral contents. Furthermore, according to the principal component analysis, three principal components of the different mineral contents were extracted to explain 96.60% of the cumulative variances. In summary, these findings demonstrated that germination represented a feasible approach to regulating and controlling the distribution of the mineral elements in brown rice, optimizing the levels of the mineral contents, and thus reducing the potential health risks.

12.
Phys Chem Chem Phys ; 26(11): 9051-9059, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38441317

RESUMO

Tuning the polarity of charge carriers at a single-molecular level is essential for designing complementary logic circuits in the field of molecular electronics. Herein, the transport properties of N-heterocyclic carbene (NHC)-linked single-molecule junctions are investigated using the ab initio quantum transport approach. The results reveal that the hydrogen atoms in NHCs function as a switch for regulating the polarity of charge carriers. Dehydrogenation changes the chemical nature of NHC anchors, thereby rendering holes as the major charge carriers rather than electrons. Essentially, dehydrogenation changes the anchoring group from electron-rich to electron-deficient. The electrons transferred to molecules from the electrodes raise the molecular level closer to the Fermi level, thus resulting in charge carrier polarity conversion. This conversion is influenced by the position and number of hydrogen atoms in the NHC anchors. To efficiently and decisively alter charge carrier polarity via atomic manipulation, a methyl substitution approach is developed and verified. These results confirm that atomic manipulation is a significant method for modulating the polarity of charge carriers in NHC-based single-molecule devices.

13.
J Refract Surg ; 40(3): e164-e172, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38466765

RESUMO

PURPOSE: To evaluate the dynamic changes in anterior segment parameters during accommodation following Implantable Collamer Lens (ICL) implantation with swept-source optical coherence tomography (SS-OCT). METHODS: Under the accommodation of 0.00 diopters (D), 3.00 D, and maximum amplitude, SS-OCT was used to examine the anterior segment parameters, including ICL vault, ICL depth (the distance between the corneal endothelium and the posterior surface of ICL), crystalline lens thickness, anterior chamber depth, and various parameters of the anterior chamber angle, comprising angle opening distance, angle recess area, trabecular iris space area, and trabecular iris angle. RESULTS: During accommodation, the ICL vault showed a significant decrease from baseline (536 ± 278 µm) to 3.00 D (522 ± 281 µm), followed by an increase from 3.00 D to maximum amplitude (548 ± 306 µm) (analysis of variance [ANOVA], P < .001). Four eyes (2.61%) exhibited a decrease in ICL vault to less than 100 µm (47 ± 32 µm) at maximum accommodation. The ICL depth decreased significantly as accommodation increased (ANOVA, P < .001). Crystalline lens thickness increased, whereas anterior chamber depth decreased during accommodation (ANOVA, P < .001). The anterior chamber angle widened during 3.00 D of accommodation but narrowed at maximum accommodation, leading to significant changes in the angle opening distance, angle recess area, trabecular iris space area, and trabecular iris angle during accommodation (ANOVA, P < .001 for all). CONCLUSIONS: The anterior segment, including ICL vault and anterior chamber angle, undergo significant dynamic changes during accommodation. These accommodative changes may require careful monitoring for the surgery design of ICL implantation. [J Refract Surg. 2024;40(3):e164-e172.].


Assuntos
Cristalino , Miopia , Lentes Intraoculares Fácicas , Humanos , Implante de Lente Intraocular/métodos , Miopia/cirurgia , Acomodação Ocular , Câmara Anterior/diagnóstico por imagem , Pseudofacia/cirurgia , Tomografia de Coerência Óptica , Biometria
15.
Asian J Psychiatr ; 95: 103997, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38492442

RESUMO

BACKGROUND: Depression is a prevalent mood disorder during the perioperative period, with both preoperative concurrent depression and new-onset postoperative depression impacting postoperative recovery. Recent studies have indicated that the dissociative anesthetic esketamine may alleviate perioperative depressive symptoms. OBJECTIVE: This meta-analysis aimed to assess the efficacy and safety of esketamine in treating perioperative depression. METHODS: We selected randomized controlled trials comparing esketamine to placebo in terms of postoperative depressive symptoms. The primary outcome was postoperative depression scores, with secondary outcomes including the prevalence of postoperative depression, pain scores using the Visual Analogue Scale or Numeric Rating Scale, and incidences of adverse reactions such as nausea/vomiting, dizziness, dreams/nightmares, hallucinations. RESULTS: We enrolled a total of 17 studies involving 2462 patients. The esketamine group demonstrated a significant reduction in postoperative depression scores within one week after surgery (SMD -0.47, 95% CI (-0.66, -0.27), P < 0.001) and over the long term (SMD -0.44, 95% CI (-0.79, -0.09), P = 0.01). Furthermore, esketamine significantly decreased the prevalence of postoperative depression both within one week (RR 0.46, 95% CI (0.33, 0.63), P < 0.001) and over the long term (RR 0.50, 95% CI (0.36, 0.70), P < 0.001). Additionally, esketamine effectively relieved pain on the first postoperative day compared to control. However, it also increased the risks of dizziness and hallucinations for a short time. CONCLUSION: This meta-analysis suggests that the intraoperative or postoperative application of esketamine could be a potentially effective treatment for perioperative depression, although the increased risk of adverse reactions should be considered.

16.
Planta ; 259(5): 98, 2024 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-38522041

RESUMO

MAIN CONCLUSION: A stable genetic transformation system for Erigeron breviscapus was developed. We cloned the EbYUC2 gene and genetically transformed it into Arabidopsis thaliana and E. breviscapus. The leaf number, YUC2 gene expression, and the endogenous auxin content in transgenic plants were significantly increased. Erigeron breviscapus is a prescription drug for the clinical treatment of cardiovascular and cerebrovascular diseases. The rosette leaves have the highest content of the major active compound scutellarin and are an important component in the yield of E. breviscapus. However, little is known about the genes related to the leaf number and flowering time of E. breviscapus. In our previous study, we identified three candidate genes related to the leaf number and flowering of E. breviscapus by combining resequencing data and genome-wide association study (GWAS). However, their specific functions remain to be characterized. In this study, we cloned and transformed the previously identified full-length EbYUC2 gene into Arabidopsis thaliana, developed the first stable genetic transformation system for E. breviscapus, and obtained the transgenic plants overexpressing EbYUC2. Compared with wild-type plants, the transgenic plants showed a significant increase in the number of leaves, which was correlated with the increased expression of EbYUC2. Consistently, the endogenous auxin content, particularly indole-3-acetic acid, in transgenic plants was also significantly increased. These results suggest that EbYUC2 may control the leaf number by regulating auxin biosynthesis, thereby laying a foundation for revealing the molecular mechanism governing the leaf number and flowering time of E. breviscapus.


Assuntos
Arabidopsis , Erigeron , Erigeron/genética , Arabidopsis/genética , Estudo de Associação Genômica Ampla , Ácidos Indolacéticos , Folhas de Planta/genética , Plantas Geneticamente Modificadas , Transformação Genética
17.
Math Biosci Eng ; 21(2): 1844-1856, 2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38454663

RESUMO

Liver rupture repair surgery serves as one tool to treat liver rupture, especially beneficial for cases of mild liver rupture hemorrhage. Liver rupture can catalyze critical conditions such as hemorrhage and shock. Surgical workflow recognition in liver rupture repair surgery videos presents a significant task aimed at reducing surgical mistakes and enhancing the quality of surgeries conducted by surgeons. A liver rupture repair simulation surgical dataset is proposed in this paper which consists of 45 videos collaboratively completed by nine surgeons. Furthermore, an end-to-end SA-RLNet, a self attention-based recurrent convolutional neural network, is introduced in this paper. The self-attention mechanism is used to automatically identify the importance of input features in various instances and associate the relationships between input features. The accuracy of the surgical phase classification of the SA-RLNet approach is 90.6%. The present study demonstrates that the SA-RLNet approach shows strong generalization capabilities on the dataset. SA-RLNet has proved to be advantageous in capturing subtle variations between surgical phases. The application of surgical workflow recognition has promising feasibility in liver rupture repair surgery.


Assuntos
Fígado , Redes Neurais de Computação , Humanos , Fluxo de Trabalho , Simulação por Computador , Fígado/cirurgia , Hemorragia/cirurgia
19.
Int J Biol Macromol ; 266(Pt 1): 131198, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38552700

RESUMO

The metabolic process of polysaccharides in gastrointestinal digestions and the effects of the resulting carbohydrates on the composition of gut microbes are important to explore their prebiotic properties. Therefore, the purpose of this study was to investigate the simulated digestion and fecal fermentation in vitro of three fractions (PHEPSs-1, PHEPSs-2 and PHEPSs-3) purified from the crude exopolysaccharides of Paecilomyces hepiali HN1 (PHEPSs) and to explore the potential prebiotic mechanisms. The three purified fractions were characterized by HPLC, UV, FT-IR, SEM and AFM, and they were all of galactoglucomannan family with molecular weight of 178, 232 and 119 kDa, respectively. They could resist the simulated gastrointestinal digestions, but they were metabolized in fecal fermentation in vitro. Furthermore, the mannose in PHEPSs showed a higher utilization rate than that of glucose or galactose. The proliferation effects of PHEPSs on Bifidobacterium and Lactobacillus were weaker significantly than those of fructooligosaccharides before 12 h of fecal fermentation, but stronger after 24 h of fecal fermentation. Meanwhile, higher levels of short-chain fatty acids were found in PHEPSs groups when the fecal fermentation extended to 36 h. Therefore, PHEPSs are expected to have a potent gut healthy activity and can be explored as functional food ingredients.

20.
World J Gastroenterol ; 30(5): 485-498, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38414591

RESUMO

BACKGROUND: Gastric cancer (GC) is associated with high mortality rates. Bile acids (BAs) reflux is a well-known risk factor for GC, but the specific mechanism remains unclear. During GC development in both humans and animals, BAs serve as signaling molecules that induce metabolic reprogramming. This confers additional cancer phenotypes, including ferroptosis sensitivity. Ferroptosis is a novel mode of cell death characterized by lipid peroxidation that contributes universally to malignant progression. However, it is not fully defined if BAs can influence GC progression by modulating ferroptosis. AIM: To reveal the mechanism of BAs regulation in ferroptosis of GC cells. METHODS: In this study, we treated GC cells with various stimuli and evaluated the effect of BAs on the sensitivity to ferroptosis. We used gain and loss of function assays to examine the impacts of farnesoid X receptor (FXR) and BTB and CNC homology 1 (BACH1) overexpression and knockdown to obtain further insights into the molecular mechanism involved. RESULTS: Our data suggested that BAs could reverse erastin-induced ferroptosis in GC cells. This effect correlated with increased glutathione (GSH) concentrations, a reduced GSH to oxidized GSH ratio, and higher GSH peroxidase 4 (GPX4) expression levels. Subsequently, we confirmed that BAs exerted these effects by activating FXR, which markedly increased the expression of GSH synthetase and GPX4. Notably, BACH1 was detected as an essential intermediate molecule in the promotion of GSH synthesis by BAs and FXR. Finally, our results suggested that FXR could significantly promote GC cell proliferation, which may be closely related to its anti-ferroptosis effect. CONCLUSION: This study revealed for the first time that BAs could inhibit ferroptosis sensitivity through the FXR-BACH1-GSH-GPX4 axis in GC cells. This work provided new insights into the mechanism associated with BA-mediated promotion of GC and may help identify potential therapeutic targets for GC patients with BAs reflux.


Assuntos
Ferroptose , Neoplasias Gástricas , Animais , Humanos , Ácidos e Sais Biliares , Transdução de Sinais
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