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1.
PLoS Pathog ; 20(9): e1012533, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39231185

RESUMEN

The body temperature of Warm-blooded hosts impedes and informs responses of bacteria accustomed to cooler environments. The second messenger c-di-GMP modulates bacterial behavior in response to diverse, yet largely undiscovered, stimuli. A long-standing debate persists regarding whether a local or a global c-di-GMP pool plays a critical role. Our research on a Stenotrophomonas maltophilia strain thriving at around 28°C, showcases BtsD as a thermosensor, diguanylate cyclase, and effector. It detects 37°C and diminishes c-di-GMP synthesis, resulting in a responsive sequence: the periplasmic c-di-GMP level is decreased, the N-terminal region of BtsD disengages from c-di-GMP, activates the two-component signal transduction system BtsKR, and amplifies sod1-3 transcription, thereby strengthening the bacterium's pathogenicity and adaptation during infections in 37°C warm Galleria mellonella larvae. This revelation of a single-protein c-di-GMP module introduces unrecognized dimensions to the functional and structural paradigms of c-di-GMP modules and reshapes our understanding of bacterial adaptation and pathogenicity in hosts with a body temperature around 37°C. Furthermore, the discovery of a periplasmic c-di-GMP pool governing BtsD-BtsK interactions supports the critical role of a local c-di-GMP pool.


Asunto(s)
Proteínas Bacterianas , GMP Cíclico , Infecciones por Bacterias Gramnegativas , Stenotrophomonas maltophilia , Stenotrophomonas maltophilia/metabolismo , GMP Cíclico/análogos & derivados , GMP Cíclico/metabolismo , Animales , Infecciones por Bacterias Gramnegativas/microbiología , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/genética , Transducción de Señal , Temperatura Corporal/fisiología , Regulación Bacteriana de la Expresión Génica , Liasas de Fósforo-Oxígeno/metabolismo , Liasas de Fósforo-Oxígeno/genética
2.
Bioresour Technol ; : 131457, 2024 Sep 14.
Artículo en Inglés | MEDLINE | ID: mdl-39284373

RESUMEN

The integration of biochar into microbial Chain Elongation (CE) proves to be an effective tool of producing high-value bio-based products. This study innovatively applied biochar fabricated under microwave irradiation with carbon fiber cloth assistance into CE system. Results highlighted that microwave biochar achieved maximal CE efficiency yielding 8 g COD/L, with 3-fold increase to the blank group devoid of any biochar. Microwave biochar also obtained the highest substrate utilization rate of 94 %, while conventional biochar group recorded 90 % and the blank group was of 74 %. Mechanistic insights revealed that the reductive surface properties facilitated CE performance, which is relevant to fostering dominant genera of Parabacteroides, Bacteroides, and Macellibacteroides. By metagenomics, microwave biochar up-regulated functional genes and enzymes involved in CE process including ethanol oxidation, the reverse ß-oxidation pathway, and the fatty acid biosynthesis pathway. This study effectively facilitated caproate production by utilizing a new microwave biochar preparation strategy.

3.
Adv Sci (Weinh) ; : e2403797, 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38981016

RESUMEN

Lithium metal batteries (LMBs) have emerged in recent years as highly promising candidates for high-density energy storage systems. Despite their immense potential, mutual constraints arise when optimizing energy density, rate capability, and operational safety, which greatly hinder the commercialization of LMBs. The utilization of oriented structures in LMBs appears as a promising strategy to address three key performance barriers: 1) low efficiency of active material utilization at high surface loading, 2) easy formation of Li dendrites and damage to interfaces under high-rate cycling, and 3) low ionic conductivity of solid-state electrolytes in high safety LMBs. This review aims to holistically introduce the concept of oriented structures, provide criteria for quantifying the degree of orientation, and elucidate their systematic effects on the properties of materials and devices. Furthermore, a detailed categorization of oriented structures is proposed to offer more precise guidance for the design of LMBs. This review also provides a comprehensive summary of preparation techniques for oriented structures and delves into the mechanisms by which these can enhance the energy density, rate capability, and safety of LMBs. Finally, potential applications of oriented structures in LMBs and the crucial challenges that need to be addressed in this field are explored.

4.
Bioorg Med Chem Lett ; 109: 129822, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-38823728

RESUMEN

The quest for novel antibacterial agents is imperative in the face of escalating antibiotic resistance. Naturally occurring tetrahydro-ß-carboline (THßC) alkaloids have been highlighted due to their significant biological derivatives. However, these structures have been little explored for antibacterial drugs development. In this study, a series of 1,2,3,4-THßC derivatives were synthesized and assessed for their antibacterial prowess against both gram-positive and gram-negative bacteria. The compounds exhibited moderate to good antibacterial activity, with some compounds showing superior efficacy against gram-positive bacteria, especially methicillin-resistant Staphylococcus aureus (MRSA), to that of Gentamicin. Among these analogs, compound 3k emerged as a hit compound, demonstrating rapid bactericidal action and a significant post-antibacterial effect, with significant cytotoxicity towards human LO2 and HepG2 cells. In addition, compound 3k (10 mg/kg) showed comparable anti-MRSA efficacy to Ciprofloxacin (2 mg/kg) in a mouse model of abdominal infection. Overall, the present findings suggested that THßC derivatives based on the title compounds hold promising applications in the development of antibacterial drugs.


Asunto(s)
Antibacterianos , Carbolinas , Bacterias Gramnegativas , Bacterias Grampositivas , Pruebas de Sensibilidad Microbiana , Antibacterianos/farmacología , Antibacterianos/síntesis química , Antibacterianos/química , Carbolinas/farmacología , Carbolinas/química , Carbolinas/síntesis química , Humanos , Relación Estructura-Actividad , Animales , Ratones , Bacterias Grampositivas/efectos de los fármacos , Estructura Molecular , Bacterias Gramnegativas/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Células Hep G2 , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos
5.
PLoS One ; 19(6): e0304522, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38837993

RESUMEN

BACKGROUND: A subset of individuals (10-20%) experience post-COVID condition (PCC) subsequent to initial SARS-CoV-2 infection, which lacks effective treatment. PCC carries a substantial global burden associated with negative economic and health impacts. This study aims to evaluate the association between plasma taurine levels with self-reported symptoms and adverse clinical outcomes in patients with PCC. METHODS AND FINDINGS: We analyzed the plasma proteome and metabolome of 117 individuals during their acute COVID-19 hospitalization and at the convalescence phase six-month post infection. Findings were compared with 28 age and sex-matched healthy controls. Plasma taurine levels were negatively associated with PCC symptoms and correlated with markers of inflammation, tryptophan metabolism, and gut dysbiosis. Stratifying patients based on the trajectories of plasma taurine levels during six-month follow-up revealed a significant association with adverse clinical events. Increase in taurine levels during the transition to convalescence were associated with a reduction in adverse events independent of comorbidities and acute COVID-19 severity. In a multivariate analysis, increased plasma taurine level between acute and convalescence phase was associated with marked protection from adverse clinical events with a hazard ratio of 0.13 (95% CI: 0.05-0.35; p<0.001). CONCLUSIONS: Taurine emerges as a promising predictive biomarker and potential therapeutic target in PCC. Taurine supplementation has already demonstrated clinical benefits in various diseases and warrants exploration in large-scale clinical trials for alleviating PCC.


Asunto(s)
COVID-19 , SARS-CoV-2 , Taurina , Humanos , Taurina/sangre , COVID-19/sangre , COVID-19/complicaciones , Femenino , Masculino , Persona de Mediana Edad , SARS-CoV-2/aislamiento & purificación , Adulto , Biomarcadores/sangre , Anciano , Síndrome Post Agudo de COVID-19 , Estudios de Casos y Controles , Metaboloma , Carga Sintomática
6.
ACS Appl Mater Interfaces ; 16(22): 28570-28577, 2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38769608

RESUMEN

Despite being heralded as the "holy grail" of anodes for their high theoretical specific capacity, lithium (Li) metal anodes still face practical challenges due to difficulties in fabricating ultrathin Li with controllable thickness and suppressing Li dendrites growth. Herein, we introduce a simple and cost-effective dip-coating method to fabricate ultrathin lithium-tin (LiSn) anode with adjustable thicknesses ranging from 4.5 to 45 µm. The in situ formation of Li22Sn5 alloy improves the wettability of the molten Li, enabling the casting of ultrathin Li metal layers on different substrates. More importantly, the abundant Li22Sn5 lithiophilic sites significantly lower the nucleation overpotential, inducing uniform Li deposition and accelerating the electrochemical reaction at the interface. As a result, the symmetric cell assembled with LiSn-Cu electrodes can cycle stably for more than 120 h with a charge/discharge depth of 50%, which is 1.5 times longer than the lifespan of the pure Li anode. In the full cells paired with NCM cathode, the discharge specific capacity is improved from 13.84 to 70.31 mA h g-1 with the LiSn-Cu anode at 8 C. The LiSn-Cu||NCM full cell realized a high energy density of 724.9 Wh kg-1 at the active material level with an N/P ratio of 1.4.

7.
PLoS One ; 19(4): e0299234, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38630770

RESUMEN

OBJECTIVES: The goal of this investigation was to identify the main compounds and the pharmacological mechanism of the traditional Chinese medicine formulation, Gong Ying San (GYS), by infrared spectral absorption characteristics, metabolomics, network pharmacology, and molecular-docking analysis for mastitis. The antibacterial and antioxidant activities were determined in vitro. METHODS: The chemical constituents of GYS were detected by ultra-high-performance liquid chromatography Q-extractive mass spectrometry (UHPLC-QE-MS). Related compounds were screened from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP, http://tcmspw.com/tcmsp.php) and the Encyclopedia of Traditional Chinese Medicine (ETCM, http://www.tcmip.cn/ETCM/index.php/Home/) databases; genes associated with mastitis were identified in DisGENT. A protein-protein interaction (PPI) network was generated using STRING. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment screening was conducted using the R module. Molecular-docking analyses were performed with the AutoDockTools V1.5.6. RESULTS: Fifty-four possible compounds in GYS with forty likely targets were found. The compound-target-network analysis showed that five of the ingredients, quercetin, luteolin, kaempferol, beta-sitosterol, and stigmasterol, had degree values >41.6, and the genes TNF, IL-6, IL-1ß, ICAM1, CXCL8, CRP, IFNG, TP53, IL-2, and TGFB1 were core targets in the network. Enrichment analysis revealed that pathways associated with cancer, lipids, atherosclerosis, and PI3K-Akt signaling pathways may be critical in the pharmacology network. Molecular-docking data supported the hypothesis that quercetin and luteolin interacted well with TNF-α and IL-6. CONCLUSIONS: An integrative investigation based on a bioinformatics-network topology provided new insights into the synergistic, multicomponent mechanisms of GYS's anti-inflammatory, antibacterial, and antioxidant activities. It revealed novel possibilities for developing new combination medications for reducing mastitis and its complications.


Asunto(s)
Medicamentos Herbarios Chinos , Mastitis , Animales , Femenino , Humanos , Bovinos , Farmacología en Red , Antioxidantes , Interleucina-6 , Luteolina , Fosfatidilinositol 3-Quinasas , Quercetina , Antibacterianos , Simulación del Acoplamiento Molecular , Medicina Tradicional China
8.
ISA Trans ; 148: 326-335, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38570256

RESUMEN

This paper tries to study the problem of finite-time synchronization for delayed semi-Markov reaction-diffusion systems. Based on the spatial and parametric characteristics of the considered systems, a new asynchronous boundary control scheme is proposed to ensure the finite-time synchronization of the drive and response systems. In the asynchronous boundary control scheme, only an actuator should be placed at the spatial boundary, which is more easier to implement and economical than the other non-boundary control strategies. Besides, the system parameters and controller follow two asynchronous semi-Markov chains for jumping, which is more practical than obeying one semi-Markov chain. Moreover, for the considered systems, we proposes a new lemma of finite-time stability, and by employing the inequality methods and variable substitution, we derive the criterion of finite-time synchronization and a correlative corollary. Finally, a numerical example and an application example on secure communication are carried out to support the developed approach.

9.
STAR Protoc ; 5(2): 103041, 2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38678567

RESUMEN

Here, we present a workflow for analyzing multi-omics data of plasma samples in patients with post-COVID condition (PCC). Applicable to various diseases, we outline steps for data preprocessing and integrating diverse assay datasets. Then, we detail statistical analysis to unveil plasma profile changes and identify biomarker-clinical variable associations. The last two steps discuss machine learning techniques for unsupervised clustering of patients based on their inherent molecular similarities and feature selection to identify predictive biomarkers. For complete details on the use and execution of this protocol, please refer to Wang et al.1.


Asunto(s)
Biomarcadores , COVID-19 , Aprendizaje Automático , SARS-CoV-2 , Humanos , COVID-19/sangre , COVID-19/virología , Biomarcadores/sangre , SARS-CoV-2/aislamiento & purificación , Plasma/química , Plasma/metabolismo , Proteómica/métodos , Multiómica
10.
Am Heart J ; 274: 11-22, 2024 08.
Artículo en Inglés | MEDLINE | ID: mdl-38670300

RESUMEN

BACKGROUND: Sodium-glucose cotransporter-2 (SGLT2) inhibitors are effective in adults with diabetes mellitus (DM) and heart failure (HF) based on randomized clinical trials. We compared SGLT2 inhibitor uptake and outcomes in two cohorts: a population-based cohort of all adults with DM and HF in Alberta, Canada and a specialized heart function clinic (HFC) cohort. METHODS: The population-based cohort was derived from linked provincial healthcare datasets. The specialized clinic cohort was created by chart review of consecutive patients prospectively enrolled in the HFC between February 2018 and August 2022. We examined the association between SGLT2 inhibitor use (modeled as a time-varying covariate) and all-cause mortality or deaths/cardiovascular hospitalizations. RESULTS: Of the 4,885 individuals from the population-based cohort, 64.2% met the eligibility criteria of the trials proving the effectiveness of SGLT2 inhibitors. Utilization of SGLT2 inhibitors increased from 1.2% in 2017 to 26.4% by January 2022. In comparison, of the 530 patients followed in the HFC, SGLT2 inhibitor use increased from 9.8% in 2019 to 49.1 % by March 2022. SGLT2 inhibitor use in the population-based cohort was associated with fewer all-cause mortality (aHR 0.51, 95%CI 0.41-0.63) and deaths/cardiovascular hospitalizations (aHR 0.65, 95%CI 0.54-0.77). However, SGLT2 inhibitor usage rates were far lower in HF patients without DM (3.5% by March 2022 in the HFC cohort). CONCLUSIONS: Despite robust randomized trial evidence of clinical benefit, the uptake of SGLT2 inhibitors in patients with HF and DM remains low, even in the specialized HFC. Clinical care strategies are needed to enhance the use of SGLT2 inhibitors and improve implementation.


Asunto(s)
Diabetes Mellitus Tipo 2 , Insuficiencia Cardíaca , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Humanos , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/mortalidad , Masculino , Femenino , Anciano , Persona de Mediana Edad , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/complicaciones , Hospitalización/estadística & datos numéricos , Alberta/epidemiología , Estudios de Cohortes , Causas de Muerte/tendencias
11.
RSC Med Chem ; 15(4): 1198-1209, 2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38665835

RESUMEN

Ferroptosis is a nonapoptotic, iron-catalyzed form of regulated cell death. It has been shown that high glucose (HG) could induce ferroptosis in vascular endothelial cells (VECs), consequently contributing to the development of various diseases. This study synthesized and evaluated a series of novel ferrostatin-1 (Fer-1) derivatives fused with a benzohydrazide moiety to prevent HG-induced VEC ferroptosis. Several promising compounds showed similar or improved inhibitory effects compared to positive control Fer-1. The most effective candidate 12 exhibited better protection against erastin-induced ferroptosis and high glucose-induced ferroptosis in VECs. Mechanistic studies revealed that compound 12 prevented mitochondrial damage, reduced intracellular ROS accumulation, upregulated the expression of GPX4, and decreased the amounts of ferrous ion, LPO and MDA in VECs. However, compound 12 still exhibited undesirable microsomal stability like Fer-1, suggesting the need for further optimization. Overall, the present findings highlight ferroptosis inhibitor 12 as a potential lead compound for treating ferroptosis-associated vascular diseases.

12.
Bioorg Med Chem ; 105: 117716, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38608329

RESUMEN

In this study, a series of new formylpiperazine-derived ferroptosis inhibitors were designed and synthesized based on the structure of a known ferroptosis inhibitor, ferrostatin-1 (Fer-1). The anti-ferroptosis activity of these synthetic compounds in human umbilical vein endothelial cells (HUVECs) induced by Erastin was evaluated. It was found that some of the new compounds, especially compound 26, showed potent anti-ferroptosis activity, as evidenced by its ability to restore cell viability, reduce iron accumulation, scavenge reactive oxygen species, maintain mitochondrial membrane potential, increase GSH levels, decrease LPO and MDA content, and upregulate GPX4 expression. Moreover, compound 26 exhibited superior microsomal stability than Fer-1. The present results suggest that compound 26 is a promising lead compound for the development of new ferroptosis inhibitors for the treatment of vascular diseases.


Asunto(s)
Supervivencia Celular , Ciclohexilaminas , Diseño de Fármacos , Ferroptosis , Células Endoteliales de la Vena Umbilical Humana , Piperazinas , Humanos , Ferroptosis/efectos de los fármacos , Piperazinas/farmacología , Piperazinas/síntesis química , Piperazinas/química , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Relación Estructura-Actividad , Ciclohexilaminas/farmacología , Ciclohexilaminas/química , Ciclohexilaminas/síntesis química , Supervivencia Celular/efectos de los fármacos , Estructura Molecular , Fenilendiaminas/farmacología , Fenilendiaminas/química , Fenilendiaminas/síntesis química , Relación Dosis-Respuesta a Droga , Especies Reactivas de Oxígeno/metabolismo , Compuestos Ferrosos/farmacología , Compuestos Ferrosos/química , Compuestos Ferrosos/síntesis química , Potencial de la Membrana Mitocondrial/efectos de los fármacos
13.
Eur J Med Chem ; 269: 116341, 2024 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-38518523

RESUMEN

Protein arginine methyltransferase 5 (PRMT5) and epidermal growth factor receptor (EGFR) are both involved in the regulation of various cancer-related processes, and their dysregulation or overexpression has been observed in many types of tumors. In this study, we designed and synthesized a series of 1-phenyl-tetrahydro-ß-carboline (THßC) derivatives as the first class of dual PRMT5/EGFR inhibitors. Among the synthesized compounds, 10p showed the most potent dual PRMT5/EGFR inhibitory activity, with IC50 values of 15.47 ± 1.31 and 19.31 ± 2.14 µM, respectively. Compound 10p also exhibited promising antiproliferative activity against A549, MCF7, HeLa, and MDA-MB-231 cell lines, with IC50 values below 10 µM. Molecular docking studies suggested that 10p could bind to PRMT5 and EGFR through hydrophobic, π-π, and cation-π interactions. Furthermore, 10p displayed favorable pharmacokinetic properties and oral bioavailability (F = 30.6%) in rats, and administrated orally 10p could significantly inhibit the growth of MCF7 orthotopic xenograft tumors. These results indicate that compound 10p is a promising hit compound for the development of novel and effective dual PRMT5/EGFR inhibitors as potential anticancer agents.


Asunto(s)
Antineoplásicos , Carbolinas , Humanos , Ratas , Animales , Relación Estructura-Actividad , Simulación del Acoplamiento Molecular , Línea Celular Tumoral , Proliferación Celular , Antineoplásicos/química , Receptores ErbB , Inhibidores de Proteínas Quinasas/farmacología , Ensayos de Selección de Medicamentos Antitumorales , Estructura Molecular , Proteína-Arginina N-Metiltransferasas
14.
Cell Rep Med ; 4(11): 101254, 2023 11 21.
Artículo en Inglés | MEDLINE | ID: mdl-37890487

RESUMEN

The post-acute sequelae of COVID-19 (PASC), also known as long COVID, is often associated with debilitating symptoms and adverse multisystem consequences. We obtain plasma samples from 117 individuals during and 6 months following their acute phase of infection to comprehensively profile and assess changes in cytokines, proteome, and metabolome. Network analysis reveals sustained inflammatory response, platelet degranulation, and cellular activation during convalescence accompanied by dysregulation in arginine biosynthesis, methionine metabolism, taurine metabolism, and tricarboxylic acid (TCA) cycle processes. Furthermore, we develop a prognostic model composed of 20 molecules involved in regulating T cell exhaustion and energy metabolism that can reliably predict adverse clinical outcomes following discharge from acute infection with 83% accuracy and an area under the curve (AUC) of 0.96. Our study reveals pertinent biological processes during convalescence that differ from acute infection, and it supports the development of specific therapies and biomarkers for patients suffering from long COVID.


Asunto(s)
COVID-19 , Síndrome Post Agudo de COVID-19 , Humanos , Convalecencia , Multiómica , Biomarcadores , Fenotipo
15.
Curr Top Med Chem ; 23(26): 2488-2526, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37818579

RESUMEN

Diabetes mellitus (DM) is a critical global health issue, affecting nearly half a billion people worldwide, with an increasing incidence rate and mortality. Type 2 diabetes is caused by the body's inability to effectively use insulin, and approximately 95% of patients have type 2 diabetes. α-glucosidase has emerged as an important therapeutic target for the treatment of type 2 diabetes. In the past years, three α-glucosidase inhibitors have been approved for clinical use, namely acarbose, voglibose, and miglitol. However, the undesirable effects associated with these carbohydrate mimic-based α-glucosidase inhibitors have limited their clinical applications. Consequently, researchers have shifted their focus towards the development of non-carbohydrate mimic α-glucosidase inhibitors that can safely and effectively manage postprandial hyperglycemia in type 2 diabetes. Herein, this article provides an overview of the synthetic α-glucosidase inhibitors, particularly those based on heterocycles, which have been reported from 2018 to 2022. This article aims to provide useful information for medicinal chemists in further developing clinically available anti-type 2 diabetes drugs.


Asunto(s)
Diabetes Mellitus Tipo 2 , Hiperglucemia , Humanos , Inhibidores de Glicósido Hidrolasas/farmacología , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/farmacología , Hipoglucemiantes/uso terapéutico , Acarbosa , Hiperglucemia/tratamiento farmacológico , alfa-Glucosidasas
16.
Bioorg Med Chem Lett ; 95: 129468, 2023 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-37689216

RESUMEN

One effective strategy for treating atherosclerosis is to inhibit the injury of vascular endothelial cells (VECs) induced by oxidized low-density lipoprotein (oxLDL) and high glucose (HG). This study synthesized and evaluated a series of novel Nrf2 activators derived from the marine natural product phidianidine for their ability to protect human umbilical VECs against oxLDL- and HG-induced injury. The results of in vitro bioassays demonstrated that compound D-36 was the most promising Nrf2 activator, effectively inhibiting the apoptosis of HUVECs induced by oxLDL and HG. Furthermore, Nrf2 knockdown experiments confirmed that compound D-36 protected against oxLDL- and HG-induced apoptosis in HUVECs by activating the Nrf2 pathway. These findings provide important insights into a new chemotype of marine-derived Nrf2 activators that could potentially be optimized to develop effective anti-atherosclerosis agents.

17.
Front Cell Dev Biol ; 11: 1185823, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37465009

RESUMEN

Introduction: The development of skeletal muscle is regulated by regulatory factors of genes and non-coding RNAs (ncRNAs). Methods: The objective of this study was to understand the transformation of muscle fiber type in the longissimus dorsi muscle of male Ningxiang pigs at four different growth stages (30, 90, 150, and 210 days after birth, n = 3) by histological analysis and whole transcriptome sequencing. Additionally, the study investigated the expression patterns of various RNAs involved in muscle fiber transformation and constructed a regulatory network for competing endogenous RNA (ceRNA) that includes circular RNA (circRNA)/long non-coding RNA (lncRNA)-microRNA (miRNA)-messenger RNA (mRNA). Results: Histomorphology analysis showed that the diameter of muscle fiber reached its maximum at 150 days after birth. The slow muscle fiber transformation showed a pattern of initial decrease followed by an increase. 29,963 circRNAs, 2,683 lncRNAs, 986 miRNAs and 22,411 mRNAs with expression level ≥0 were identified by whole transcriptome sequencing. Furthermore, 642 differentially expressed circRNAs (DEc), 505 differentially expressed lncRNAs (DEl), 316 differentially expressed miRNAs (DEmi) and 6,090 differentially expressed mRNAs (DEm) were identified by differential expression analysis. Functions of differentially expressed mRNA were identified by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). GO enrichment analysis indicates that 40 known genes and 6 new genes are associated with skeletal muscle development. Additionally, KEGG analysis shows that these genes regulate skeletal muscle development via MAPK, FoxO, Hedgehog, PI3K-Akt, Notch, VEGF and other signaling pathways. Through protein-protein interaction (PPI) and transcription factor prediction (TFP), the action mode of skeletal muscle-related genes was explored. PPI analysis showed that there were stable interactions among 19 proteins, meanwhile, TFP analysis predicted 22 transcription factors such as HMG20B, MYF6, MYOD1 and MYOG, and 12 of the 19 interacting proteins were transcription factors. The regulatory network of ceRNA related to skeletal muscle development was constructed based on the correlation of various RNA expression levels and the targeted binding characteristics with miRNA. The regulatory network included 31 DEms, 59 miRNAs, 667 circRNAs and 224 lncRNAs. conclusion: Overall, the study revealed the role of ceRNA regulatory network in the transformation of skeletal muscle fiber types in Ningxiang pigs, which contributes to the understanding of ceRNA regulatory network in Ningxiang pigs during the skeletal muscle development period.

18.
Environ Sci Process Impacts ; 25(9): 1438-1448, 2023 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-37424387

RESUMEN

After an oil spill, the formation of oil-particle aggregates (OPAs) is associated with the interaction between dispersed oil and marine particulate matter such as phytoplankton, bacteria and mineral particles. Until recently, the combined effect of minerals and marine algae in influencing oil dispersion and OPA formation has rarely been investigated in detail. In this paper, the impacts of a species of flagellate algae Heterosigma akashiwo on oil dispersion and aggregation with montmorillonite were investigated. This study has found that oil coalescence is inhibited due to the adhesion of algal cells on the droplet surface, causing fewer large droplets to be dispersed into the water column and small OPAs to form. Due to the role of biosurfactants in the algae and the inhibition of algae on the swelling of mineral particles, both the oil dispersion efficiency and oil sinking efficiency were improved, which reached 77.6% and 23.5%, respectively at an algal cell concentration (Ca) of 1.0 × 106 cells per mL and a mineral concentration of 300 mg L-1. The volumetric mean diameter of the OPAs decreased from 38.4 µm to 31.5 µm when Ca increased from 0 to 1.0 × 106 cells per mL. At higher turbulent energy, more oil tended to form larger OPAs. The findings may add knowledge about the fate and transport of spilled oil and provide fundamental data for oil spill migration modelling.


Asunto(s)
Contaminación por Petróleo , Petróleo , Contaminantes Químicos del Agua , Petróleo/análisis , Contaminantes Químicos del Agua/análisis , Material Particulado/análisis , Sedimentos Geológicos , Contaminación por Petróleo/análisis , Minerales
19.
Int J Biol Macromol ; 247: 125742, 2023 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-37437681

RESUMEN

This study aimed to combine the active targeting function of folate (FA) receptor-mediated endocytosis with the pH-responsive drug delivery of poly (ethylene glycol)-grafted-poly (-amino ester) copolymers (PEG-PAE) in cancer targeting therapy. Herein, O-carboxymethylated chitosan (OCMC) was grafted with hydrophobic deoxycholic acid (DOCA). Further, PEG-PAE and FA-conjugated DOCA modified OCMC were synthesized to develop the potential cancer-targeted carrier (PEG-PAE-DOMC-FA), for which the structure was investigated by 1H NMR and FTIR. Then riccardin D (RD) was successfully loaded for tumor-targeted drug delivery. The particle size, zeta potential, encapsulating efficiencies, and loading content profiles of PEG-PAE-DOMC-FA/RD showed a strong dependence on the environmental pH values. The cumulative release of PEG-PAE-DOMC-FA/RD at pH 5.0 (90.63 %) was higher than pH 7.4 (51.12 %), which also indicated the pH sensitivity. Moreover, a lower IC50 and higher coumarin-6 uptake were found because of the folate-receptor-mediated endocytosis. In pharmacokinetic study, PEG-PAE-DOMC-FA/RD significantly improved the mean retention time (MRT) and AUC(0-∞) from 7.89 h and 36.1 mg/L·h of control group to 10.03 h and 123.8 mg/L·h. In the xenograft mice model, stronger antitumor efficacy and lower toxicity were confirmed. In conclusion, the multi-functional micelles could be considered as a promising vehicle for delivering hydrophobic drugs to tumors.


Asunto(s)
Quitosano , Acetato de Desoxicorticosterona , Neoplasias , Humanos , Ratones , Animales , Micelas , Quitosano/uso terapéutico , Acetato de Desoxicorticosterona/uso terapéutico , Polietilenglicoles/química , Neoplasias/tratamiento farmacológico , Ácido Fólico/química , Concentración de Iones de Hidrógeno , Portadores de Fármacos/química , Línea Celular Tumoral
20.
Food Funct ; 14(14): 6410-6421, 2023 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-37366339

RESUMEN

Probiotics have long been utilized as functional food and modulate gut microbial homeostasis, but their colonization niche is mostly unclear and transient, which restrains the development of microbiome-targeted strategies. Lactiplantibacillus (L.) plantarum ZDY2013 is an allochthonous species of the human gastrointestinal tract with acid-tolerant properties. It serves as an antagonistic agent against the food-borne pathogen Bacillus (B.) cereus and a potent regulator of the gut microbiota. However, there is a knowledge gap regarding the colonization dynamics of L. plantarum ZDY2013 in the host intestine and the colonization niche of its interaction with pathogens. Here, we designed a pair of specific primers targeting L. plantarum ZDY2013 based on its whole genome sequence. We evaluated their accuracy and sensitivity with other host-derived strains and confirmed their availability with artificially spiked fecal samples from different mouse models. Additionally, the content of L. plantarum ZDY2013 was quantified by qPCR in fecal samples from BALB/c mice, followed by the analysis of its colonization niche preference. Moreover, the interactions between L. plantarum ZDY2013 and enterotoxigenic B. cereus HN001 were also elucidated. The results revealed that the newly designed primers could identify L. plantarum ZDY2013 with high specificity and were resistant to the influence of the complex fecal matrix and gut microbes from different hosts. Interestingly, the content of mixed L. plantarum ZDY2013 and B. cereus HN001 when orally administered remained higher when compared with the single strain group in BALB/c mice upon discontinuation of intragastric administration. In addition, L. plantarum ZDY2013 was mainly enriched in the large intestine during the ingestion period and maintained the highest content in the stomach after discontinuing supplementation on day 7. Moreover, L. plantarum ZDY2013 colonization neither damaged the intestine nor ameliorated the damage triggered by B. cereus in BALB/c mice. Overall, our study constructed two efficient specific primers targeting L. plantarum ZDY2013 and provided the potential to explore the underlying mechanism of competition between L. plantarum ZDY2013 and pathogens in host species.


Asunto(s)
Lactobacillus plantarum , Probióticos , Humanos , Animales , Ratones , Bacillus cereus/genética , Lactobacillus plantarum/genética , Tracto Gastrointestinal , Heces
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