Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 82
Filtrar
1.
J Endovasc Ther ; : 15266028241286808, 2024 Oct 22.
Artículo en Inglés | MEDLINE | ID: mdl-39435977

RESUMEN

OBJECTIVE: To evaluate the long-term outcomes of the provisional extension to induce complete attachment technique (PETTICOAT) for the treatment of acute and subacute complicated type B aortic dissection (TBAD). METHODS: We retrospectively collected and analyzed the clinical data of patients with acute and subacute TBAD who were treated using the PETTICOAT technique at our center between March 2014 and March 2023. The primary endpoint was all-cause mortality; secondary endpoints were a composite of complications, such as entry flow, stent-graft-induced new entry (SINE), and re-intervention. RESULTS: The technical success was 92% (46/50). The perioperative mortality was 2% (1/50), and the procedure-related re-intervention was also 2% (1/50). The mean follow-up time was (74.9±33.9) months. The mortality was 4.1% (2/49). The incidence of aortic-related complications was 8.2% (4/49), including new entry flow, 2 retrograde type A aortic dissections, and 1 distal stent graft-induced new entry SINE. The procedure-related re-intervention rate was 4.1% (2/49). After 5 years of follow-up, the total aortic diameter at the renal artery level was reduced from that at the third year of follow-up but was still significantly larger than preoperatively (26.9±6.6 mm vs. 24.1±4.2 mm, p=0.013). While at the covered stent, bare stent, stentless, and celiac artery (CA) levels, the total aortic diameters did not change significantly compared with preoperative values, whereas true lumen (TL) diameters and TL ratios were maintained at obviously higher levels than preoperative. The rate of complete thrombosis of false lumen in the thoracic aortic segment was significantly higher than that in the abdominal aortic segment (79.6% vs 30.6%, p=0.0001). CONCLUSIONS: The results indicated that the PETTICOAT technique is safe and effective and could promote positive remodeling of the aorta from the level of the covered stent to the CA. Remodeling of the distal abdominal aorta may fluctuate and requires close follow-up review. CLINICAL IMPACT: The long-term results from our center suggest that the PETTICOAT technique promotes positive remodeling of the aorta from the level of the covered stent to the CA; whereas this advantage does not seem to be significant in the more distal segment of the abdominal aorta, mainly at the level of RA and distal. Therefore, further procedures may be required for aortic dissection of the abdominal segment. In addition, aortic remodeling may fluctuate to some extent during the follow-up period, especially in the abdominal visceral region, so close follow-up review is quite important, and prompt re-intervention is required if necessary.

2.
J Environ Manage ; 370: 122556, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-39357450

RESUMEN

Seeking highly efficient adsorbents for pharmaceuticals and personal care products (PPCPs) removal has been a worldwide continuing endeavor. In this study, a new 3D composite material was synthesized by covalently anchoring Poly(m-Phenylenediamine) onto 3D polyvinyl alcohol modified foam framework (PmPD-MF-PVA). PmPD-MF-PVA was characterized and evaluated for its efficacy in removing diclofenac (DCF), a commonly detected PPCPs in both wastewater and surface water. Results showed that the adsorption capacity of PmPD-MF-PVA toward DCF was 1.5 times higher than that of PmPD-MF. The addition of PVA increased deposition area of PmPD, and promoted PmPD loading on the foam surface. Batch adsorption experiments exhibited that the adsorption of DCF was fitted well with Langmuir isotherm and pseudo-second-order kinetic models. The maximum adsorption capacity of PmPD-MF-PVA was 115 mg/g. Meanwhile, PmPD-MF-PVA exhibited better separation ability than the hard-to-separate PmPD. Characterization analysis and density functional theory (DFT) calculation elucidated the main mechanisms of DCF adsorption on PmPD-MF-PVA. Hydrogen bonding and π-π interactions were main drivers for DCF adsorption, followed by electrostatic attraction and hydrophobic forces. This study provides an effective strategy to overcome the drawbacks of PmPD, such as recycling difficulty and agglomeration problems, offering valuable insights for the design of polymers-based adsorbents.

3.
Acta Pharmacol Sin ; 2024 Sep 23.
Artículo en Inglés | MEDLINE | ID: mdl-39313515

RESUMEN

Acetaminophen (APAP) overdose-induced acute liver injury (ALI) is characterized by extensive oxidative stress, and the clinical interventions for this adverse effect remain limited. Astilbin is an active compound found in the rhizome of Smilax glabra Roxb. with anti-inflammatory and antioxidant activities. Due to its low oral bioavailability, astilbin can accumulate in the intestine, which provides a basis for the interaction between astilbin and gut microbiota (GM). In the present study we investigated the protective effects of astilbin against APAP-induced ALI by focusing on the interaction between astilbin and GM. Mice were treated with astilbin (50 mg·kg-1·d-1, i.g.) for 7 days. After the last administration of astilbin for 2 h, the mice received APAP (300 mg/kg, i.g.) to induce ALI. We showed that oral administration of astilbin significantly alleviated APAP-induced ALI by altering the composition of GM and enriching beneficial metabolites including hydroxytyrosol (HT). GM depletion using an "antibiotics cocktail" or paraoral administration of astilbin abolished the hepatoprotective effects of astilbin. On the other hand, administration of HT (10 mg/kg, i.g.) caused similar protective effects in APAP-induced ALI mice. Transcriptomic analysis of the liver tissue revealed that HT inhibited reactive oxygen species and inflammation-related signaling in APAP-induced ALI; HT promoted activation of the Nrf2 signaling pathway to combat oxidative stress following APAP challenge in a sirtuin-6-dependent manner. These results highlight that oral astilbin ameliorates APAP-induced ALI by manipulating the GM and metabolites towards a more favorable profile, and provide an alternative therapeutic strategy for alleviating APAP-induced ALI.

4.
J Endovasc Ther ; : 15266028241283324, 2024 Sep 29.
Artículo en Inglés | MEDLINE | ID: mdl-39342458

RESUMEN

OBJECTIVES: Stent graft-related aortic injury is a major complication after thoracic endovascular aortic repair (TEVAR) and seriously affects patient prognosis. However, the distribution characteristics of aortic wall stress under the action of stent grafts and the mechanism of abnormal wall stress leading to aortic wall injury and adverse remodeling were unclear. The aim of this study was to explore the potential mechanisms of high wall stress on the structural and functional alterations of the aortic wall by combining animal experiments, numerical simulations, and bioinformatics. METHODS: We observed stent graft-induced aortic injury by performing fenestrated TEVAR in 6 pigs, and quantitatively analyzed and visualized the stress distribution of the aortic wall under the stent graft through numerical simulation. Hematoxylin and eosin (HE) staining, Masson's trichrome staining, Verhoeff's Van Gieson (EVG) staining, and immunostaining were used to evaluate pathological changes in the aorta. Based on the numerical simulation results, the corresponding high-stress and low-stress regions of the aortic wall were subjected to bulk-RNA sequencing, and hub genes were identified by bioinformatics analysis. RESULTS: Stent grafts were successfully implanted in 5 pigs. In all computational models, we found that obvious deformation and characteristic maximum stress concentration occurred on the side of the greater curve of the aortic arch in contact with the stent graft tip, and the high wall stress concentration areas were highly consistent with the obvious pathological injury area. Subsequent pathological analysis revealed that high wall stress-induced confusion and fragmentation of elastic fibers, collagen deposition, loss and phenotypic switching of vascular smooth muscle cells, and increased inflammatory responses. Gene expression profiles of the aortic wall under different wall stress conditions were described for the first time, and the hub genes (TGFB1, CDH5, DCN, ITGA5, ITGB3, and WT1) that may be involved in regulating the aortic injury and remodeling process in response to high wall stress stimulation were identified. CONCLUSIONS: This study revealed a panoramic view of stent graft-associated high wall stress-induced aortic wall injury through technical approaches of multiple dimensions. Understanding these biomechanical features and hub genes is pivotal for advancing our comprehension of the complications associated with aortic injury after TEVAR and facilitating the development of future therapeutic interventions. CLINICAL IMPACT: This study revealed a panoramic view of stent graft-associated high wall stress-induced aortic wall injury through technical approaches of multiple dimensions. The biomechanical distribution characteristics of the aortic wall, the secondary pathological injury and the alteration of gene expression profile under the action of stent graft were comprehensively revealed by animal experiments for the first time. This will advance clinicians' comprehension of complications associated with aortic injury after TEVAR, provide a new biomechanical perspective for the rational preoperative planning of TEVAR and the management of postoperative complications, and facilitate the development of future therapeutic interventions and stent graft device designs.

6.
Emerg Microbes Infect ; 13(1): 2372344, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38916407

RESUMEN

The Orthopoxvirus (OPXV) genus of the Poxviridae includes human pathogens variola virus (VARV), monkeypox virus (MPXV), vaccinia virus (VACV), and a number of zoonotic viruses. A number of Bcl-2-like proteins of VACV are involved in escaping the host innate immunity. However, little work has been devoted to the evolution and function of their orthologues in other OPXVs. Here, we found that MPXV protein P2, encoded by the P2L gene, and P2 orthologues from other OPXVs, such as VACV protein N2, localize to the nucleus and antagonize interferon (IFN) production. Exceptions to this were the truncated P2 orthologues in camelpox virus (CMLV) and taterapox virus (TATV) that lacked the nuclear localization signal (NLS). Mechanistically, the NLS of MPXV P2 interacted with karyopherin α-2 (KPNA2) to facilitate P2 nuclear translocation, and competitively inhibited KPNA2-mediated IRF3 nuclear translocation and downstream IFN production. Deletion of the NLS in P2 or orthologues significantly enhanced IRF3 nuclear translocation and innate immune responses, thereby reducing viral replication. Moreover, deletion of NLS from N2 in VACV attenuated viral replication and virulence in mice. These data demonstrate that the NLS-mediated translocation of P2 is critical for P2-induced inhibition of innate immunity. Our findings contribute to an in-depth understanding of the mechanisms of OPXV P2 orthologue in innate immune evasion.


Asunto(s)
Inmunidad Innata , Factor 3 Regulador del Interferón , Monkeypox virus , Señales de Localización Nuclear , Proteínas Virales , Animales , Factor 3 Regulador del Interferón/metabolismo , Factor 3 Regulador del Interferón/genética , Ratones , Humanos , Proteínas Virales/genética , Proteínas Virales/metabolismo , Proteínas Virales/inmunología , Señales de Localización Nuclear/genética , Monkeypox virus/genética , Monkeypox virus/inmunología , Células HEK293 , alfa Carioferinas/genética , alfa Carioferinas/metabolismo , Evasión Inmune , Núcleo Celular/metabolismo , Interferones/genética , Interferones/inmunología , Interferones/metabolismo , Infecciones por Poxviridae/inmunología , Infecciones por Poxviridae/virología , Infecciones por Poxviridae/veterinaria , Ratones Endogámicos C57BL
7.
Environ Res ; 257: 119296, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-38824985

RESUMEN

As the rapidly growing number of waste lithium-ion batteries (LIBs), the recycling and reutilization of anode graphite is of increasing interest. Converting waste anode graphite into functional materials may be a sensible option. Herein, a series of carbonaceous catalysts (TG) were successfully prepared using spent anode graphite calcined at various temperatures and applied for activating peroxymonosulfate (PMS) to degrade atrazine (ATZ). The catalyst obtained at 800 °C (TG-800) showed the optimum performance for ATZ removal (99.2% in 6 min). Various experimental conditions were explored to achieve the optimum efficiency of the system. In the TG-800/PMS system, free radicals (e.g., SO4·-, HO·), singlet oxygen (1O2), together with a direct electron transfer pathway all participated in ATZ degradation, and the ketonic (CO) group was proved as the leading catalytic site for PMS activation. The potential degradation routes of ATZ have also been presented. According to the toxicity assessment experiments, the toxicity of the intermediate products decreased. The reusability and universal applicability of the TG-800 were also confirmed. This research not only provides an efficient PMS activator for pollutant degradation, but also offers a meaningful reference for the recovery of waste anode graphite to develop environmentally functional materials.


Asunto(s)
Atrazina , Electrodos , Grafito , Peróxidos , Atrazina/química , Grafito/química , Peróxidos/química , Catálisis , Contaminantes Químicos del Agua/química , Contaminantes Químicos del Agua/análisis , Herbicidas/química
8.
Basic Clin Pharmacol Toxicol ; 135(2): 148-163, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38887973

RESUMEN

Human pregnane X receptor (PXR) is critical for regulating the expression of key drug-metabolizing enzymes such as CYP3A and CYP2C. Our recent study revealed that treatment with rodent-specific PXR agonist pregnenolone-16α-carbonitrile (PCN) significantly induced hepatomegaly and promoted liver regeneration after two-thirds partial hepatectomy (PHx) in mice. However, it remains unclear whether PXR activation induces hepatomegaly and liver regeneration and simultaneously promotes metabolic function of the liver. Here, we investigated the metabolism activity of CYP1A2, CYP3A1/2 and CYP2C6/11 during PXR activation-induced liver enlargement and regeneration in rats after cocktail dosing of CYP probe drugs. For PCN-induced hepatomegaly, a notable increase in the metabolic activity of CYP3A1/2 and CYP2C6/11, as evidenced by the plasma exposure of probe substrates and the AUC ratios of the characteristic metabolites to its corresponding probe substrates. The metabolic activity of CYP1A2, CYP3A1/2 and CYP2C6/11 decreased significantly after PHx. However, PCN treatment obviously enhanced the metabolic activity of CYP2C6/11 and CYP3A1/2 in PHx rats. Furthermore, the protein expression levels of CYP3A1/2 and CYP2C6/11 in liver were up-regulated. Taken together, this study demonstrates that PXR activation not only induces hepatomegaly and liver regeneration in rats, but also promotes the protein expression and metabolic activity of the PXR downstream metabolizing enzymes such as CYP3A1/2 and CYP2C6/11 in the body.


Asunto(s)
Citocromo P-450 CYP3A , Hepatomegalia , Regeneración Hepática , Hígado , Receptor X de Pregnano , Carbonitrilo de Pregnenolona , Animales , Receptor X de Pregnano/metabolismo , Receptor X de Pregnano/genética , Regeneración Hepática/efectos de los fármacos , Masculino , Citocromo P-450 CYP3A/metabolismo , Carbonitrilo de Pregnenolona/farmacología , Hígado/metabolismo , Hígado/enzimología , Hígado/efectos de los fármacos , Ratas , Hepatomegalia/metabolismo , Hepatomegalia/patología , Hidrocarburo de Aril Hidroxilasas/metabolismo , Hidrocarburo de Aril Hidroxilasas/genética , Familia 2 del Citocromo P450/metabolismo , Familia 2 del Citocromo P450/genética , Ratas Sprague-Dawley , Citocromo P-450 CYP1A2/metabolismo , Citocromo P-450 CYP1A2/genética , Esteroide 16-alfa-Hidroxilasa/metabolismo , Esteroide 16-alfa-Hidroxilasa/genética , Esteroide 12-alfa-Hidroxilasa/metabolismo , Esteroide 12-alfa-Hidroxilasa/genética , Hepatectomía
9.
Ann Vasc Surg ; 108: 98-111, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-38942377

RESUMEN

Advanced endovascular techniques, such as fenestrated stent grafts, are nowadays available that permit minimally invasive treatment of complex abdominal aortic aneurysms. However, thoracoabdominal aortic aneurysm patients have anatomic limitations to fenestrated stent-grafts given a large lumen, that is, the gap between the endograft and the inner aortic wall. This has led to the development of branched endovascular aneurysm repair as the ideal option for such patients. The Zenith t-Branch multibranched endograft (Cook Medical, Bloomington, IN), which has been commercially available in Europe to treat thoracoabdominal aortic aneurysm since June 2012, represents a feasible off-the-shelf alternative for treatment of such pathologies, especially in the urgent setting, for patients who cannot wait the time required for manufacturing and delivery of custom-made endografts. The device's anatomical suitability should be considered, especially for female patients with smaller iliofemoral vessels. Several tips may help deal with particularly complex scenarios (such as, for instance, in case of narrow inner aortic lumens or when treating patients with failure of prior endovascular aneurysm repair), and a broad array of techniques and devices must be available to ensure technical and clinical success. Despite promising early outcomes, concerns remain particularly regarding the risk for spinal cord ischemia and further assessment of long-term durability is needed, including the rate of target vessel instability and need for secondary interventions. As the published evidence mainly comes from retrospective registries, it is likely that reported outcomes may suffer from an intrinsic bias as most procedures reported to date have been carried out at high-volume aortic centers. Nonetheless, with the never-ceasing adoption of new and refined techniques, outcomes are expected to ameliorate.


Asunto(s)
Aneurisma de la Aorta Torácica , Implantación de Prótesis Vascular , Prótesis Vascular , Procedimientos Endovasculares , Diseño de Prótesis , Stents , Humanos , Procedimientos Endovasculares/instrumentación , Procedimientos Endovasculares/efectos adversos , Aneurisma de la Aorta Torácica/cirugía , Aneurisma de la Aorta Torácica/diagnóstico por imagen , Implantación de Prótesis Vascular/instrumentación , Implantación de Prótesis Vascular/efectos adversos , Resultado del Tratamiento , Factores de Riesgo , Complicaciones Posoperatorias/etiología , Masculino , Femenino , Aneurisma de la Aorta Toracoabdominal
10.
Nat Prod Bioprospect ; 14(1): 33, 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38771401

RESUMEN

N-Hydroxyapiosporamide (N-hydap), a marine product derived from a sponge-associated fungus, has shown promising inhibitory effects on small cell lung cancer (SCLC). However, there is limited understanding of its metabolic pathways and characteristics. This study explored the in vitro metabolic profiles of N-hydap in human recombinant cytochrome P450s (CYPs) and UDP-glucuronosyltransferases (UGTs), as well as human/rat/mice microsomes, and also the pharmacokinetic properties by HPLC-MS/MS. Additionally, the cocktail probe method was used to investigate the potential to create drug-drug interactions (DDIs). N-Hydap was metabolically unstable in various microsomes after 1 h, with about 50% and 70% of it being eliminated by CYPs and UGTs, respectively. UGT1A3 was the main enzyme involved in glucuronidation (over 80%), making glucuronide the primary metabolite. Despite low bioavailability (0.024%), N-hydap exhibited a higher distribution in the lungs (26.26%), accounting for its efficacy against SCLC. Administering N-hydap to mice at normal doses via gavage did not result in significant toxicity. Furthermore, N-hydap was found to affect the catalytic activity of drug metabolic enzymes (DMEs), particularly increasing the activity of UGT1A3, suggesting potential for DDIs. Understanding the metabolic pathways and properties of N-hydap should improve our knowledge of its drug efficacy, toxicity, and potential for DDIs.

11.
Small ; 20(34): e2310396, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38607299

RESUMEN

Transition metal chalcogenides (TMCs) are widely used in photocatalytic fields such as hydrogen evolution, nitrogen fixation, and pollutant degradation due to their suitable bandgaps, tunable electronic and optical properties, and strong reducing ability. The unique 2D malleability structure provides a pre-designed platform for customizable structures. The introduction of vacancy engineering makes up for the shortcomings of photocorrosion and limited light response and provides the greatest support for TMCs in terms of kinetics and thermodynamics in photocatalysis. This work reviews the effect of vacancy engineering on photocatalytic performance based on 2D semiconductor TMCs. The characteristics of vacancy introduction strategies are summarized, and the development of photocatalysis of vacancy engineering TMCs materials in energy conversion, degradation, and biological applications is reviewed. The contribution of vacancies in the optical range and charge transfer kinetics is also discussed from the perspective of structure manipulation. Vacancy engineering not only controls and optimizes the structure of the TMCs, but also improves the optical properties, charge transfer, and surface properties. The synergies between TMCs vacancy engineering and atomic doping, other vacancies, and heterojunction composite techniques are discussed in detail, followed by a summary of current trends and potential for expansion.

12.
Water Res ; 253: 121255, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38341971

RESUMEN

Tracking nitrogen pollution sources is crucial for the effective management of water quality; however, it is a challenging task due to the complex contaminative scenarios in the freshwater systems. The contaminative pattern variations can induce quick responses of aquatic microorganisms, making them sensitive indicators of pollution origins. In this study, the soil and water assessment tool, accompanied by a detailed pollution source database, was used to detect the main nitrogen pollution sources in each sub-basin of the Liuyang River watershed. Thus, each sub-basin was assigned to a known class according to SWAT outputs, including point source pollution-dominated area, crop cultivation pollution-dominated area, and the septic tank pollution-dominated area. Based on these outputs, the random forest (RF) model was developed to predict the main pollution sources from different river ecosystems using a series of input variable groups (e.g., natural macroscopic characteristics, river physicochemical properties, 16S rRNA microbial taxonomic composition, microbial metagenomic data containing taxonomic and functional information, and their combination). The accuracy and the Kappa coefficient were used as the performance metrics for the RF model. Compared with the prediction performance among all the input variable groups, the prediction performance of the RF model was significantly improved using metagenomic indices as inputs. Among the metagenomic data-based models, the combination of the taxonomic information with functional information of all the species achieved the highest accuracy (0.84) and increased median Kappa coefficient (0.70). Feature importance analysis was used to identify key features that could serve as indicators for sudden pollution accidents and contribute to the overall function of the river system. The bacteria Rhabdochromatium marinum, Frankia, Actinomycetia, and Competibacteraceae were the most important species, whose mean decrease Gini indices were 0.0023, 0.0021, 0.0019, and 0.0018, respectively, although their relative abundances ranged only from 0.0004 to 0.1 %. Among the top 30 important variables, functional variables constituted more than half, demonstrating the remarkable variation in the microbial functions among sites with distinct pollution sources and the key role of functionality in predicting pollution sources. Many functional indicators related to the metabolism of Mycobacterium tuberculosis, such as K24693, K25621, K16048, and K14952, emerged as significant important factors in distinguishing nitrogen pollution origins. With the shortage of pollution source data in developing regions, this suggested approach offers an economical, quick, and accurate solution to locate the origins of water nitrogen pollution using the metagenomic data of microbial communities.


Asunto(s)
Microbiota , Contaminantes Químicos del Agua , Nitrógeno/análisis , Ríos/química , ARN Ribosómico 16S , Contaminación del Agua/análisis , Monitoreo del Ambiente , China , Contaminantes Químicos del Agua/análisis
13.
J Sep Sci ; 47(1): e2300583, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38234034

RESUMEN

Aconite is the processed product of the seed root of Aconitum carmichaelii Debx. Aconite is a commonly used traditional Chinese medicine, which is generally used after processing. Black aconite, light aconite, and salted aconite are three different processed aconite products. They have the effects of restoring yang and saving energy enemy, dispersing cold, and relieving pain. However, clinical aconite poisoning cases have frequently been reported. In our study, we investigated the effects of three different processed aconite products on the changes of metabolites in vivo. A total of 42 rats were randomly divided into seven groups with six rats in each group. After three consecutive days of intragastric administration of 2.7 g/kg of the aconite-processed product, rat serums were obtained. The rat metabolites were detected using liquid chromatography-tandem mass spectrometry. The altered metabolites related to aconite-processed products were discovered by statistical analysis using metaboanalyst software. Our study is the first time to comprehensively evaluate the effects of three different processed aconite products on rat metabolites based on pseudotargeted metabolomics.


Asunto(s)
Aconitum , Medicamentos Herbarios Chinos , Ratas , Animales , Aconitum/química , Medicamentos Herbarios Chinos/análisis , Raíces de Plantas/química , Medicina Tradicional China , Cromatografía Liquida , Metabolómica/métodos
14.
J Hepatol ; 80(3): 454-466, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37952766

RESUMEN

BACKGROUND & AIMS: Hereditary tyrosinemia type 1 (HT1) results from the loss of fumarylacetoacetate hydrolase (FAH) activity and can lead to lethal liver injury. Therapeutic options for HT1 remain limited. In this study, we aimed to construct an engineered bacterium capable of reprogramming host metabolism and thereby provide a potential alternative approach for the treatment of HT1. METHODS: Escherichia coli Nissle 1917 (EcN) was engineered to express genes involved in tyrosine metabolism in the anoxic conditions that are characteristic of the intestine (EcN-HT). Bodyweight, survival rate, plasma (tyrosine/liver function), H&E staining and RNA sequencing were used to assess its ability to degrade tyrosine and protect against lethal liver injury in Fah-knockout (KO) mice, a well-accepted model of HT1. RESULTS: EcN-HT consumed tyrosine and produced L-DOPA (levodopa) in an in vitro system. Importantly, in Fah-KO mice, the oral administration of EcN-HT enhanced tyrosine degradation, reduced the accumulation of toxic metabolites, and protected against lethal liver injury. RNA sequencing analysis revealed that EcN-HT rescued the global gene expression pattern in the livers of Fah-KO mice, particularly of genes involved in metabolic signaling and liver homeostasis. Moreover, EcN-HT treatment was found to be safe and well-tolerated in the mouse intestine. CONCLUSIONS: This is the first report of an engineered live bacterium that can degrade tyrosine and alleviate lethal liver injury in mice with HT1. EcN-HT represents a novel engineered probiotic with the potential to treat this condition. IMPACT AND IMPLICATIONS: Patients with hereditary tyrosinemia type 1 (HT1) are characterized by an inability to metabolize tyrosine normally and suffer from liver failure, renal dysfunction, neurological impairments, and cancer. Given the overlap and complementarity between the host and microbial metabolic pathways, the gut microbiome provides a potential chance to regulate host metabolism through degradation of tyrosine and reduction of byproducts that might be toxic. Herein, we demonstrated that an engineered live bacterium, EcN-HT, could enhance tyrosine breakdown, reduce the accumulation of toxic tyrosine byproducts, and protect against lethal liver injury in Fah-knockout mice. These findings suggested that engineered live biotherapeutics that can degrade tyrosine in the gut may represent a viable and safe strategy for the prevention of lethal liver injury in HT1 as well as the mitigation of its associated pathologies.


Asunto(s)
Tirosinemias , Humanos , Ratones , Animales , Tirosinemias/complicaciones , Tirosinemias/genética , Tirosinemias/metabolismo , Hígado/patología , Modelos Animales de Enfermedad , Ratones Noqueados , Tirosina/metabolismo , Escherichia coli/genética
15.
Cell Host Microbe ; 32(1): 48-62.e9, 2024 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-38056458

RESUMEN

Acetaminophen overuse is a common cause of acute liver failure (ALF). During ALF, toxins are metabolized by enzymes such as CYP2E1 and transformed into reactive species, leading to oxidative damage and liver failure. Here, we found that oral magnesium (Mg) alleviated acetaminophen-induced ALF through metabolic changes in gut microbiota that inhibit CYP2E1. The gut microbiota from Mg-supplemented humans prevented acetaminophen-induced ALF in mice. Mg exposure modulated Bifidobacterium metabolism and enriched indole-3-carboxylic acid (I3C) levels. Formate C-acetyltransferase (pflB) was identified as a key Bifidobacterium enzyme involved in I3C generation. Accordingly, a Bifidobacterium pflB knockout showed diminished I3C generation and reduced the beneficial effects of Mg. Conversely, treatment with I3C or an engineered bacteria overexpressing Bifidobacterium pflB protected against ALF. Mechanistically, I3C bound and inactivated CYP2E1, thus suppressing formation of harmful reactive intermediates and diminishing hepatocyte oxidative damage. These findings highlight how interactions between Mg and gut microbiota may help combat ALF.


Asunto(s)
Acetaminofén , Fallo Hepático Agudo , Humanos , Ratones , Animales , Acetaminofén/efectos adversos , Acetaminofén/metabolismo , Magnesio/metabolismo , Citocromo P-450 CYP2E1/metabolismo , Citocromo P-450 CYP2E1/farmacología , Hígado/metabolismo , Fallo Hepático Agudo/inducido químicamente , Fallo Hepático Agudo/metabolismo
16.
Chemosphere ; 350: 140998, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38142881

RESUMEN

Aggregation kinetics of plastics are affected by the surface functional groups and exposure orders (electrolyte and protein) with kinds of mechanisms in aquatic environment. This study investigates the aggregation of polystyrene nanoplastics (PSNPs) with varying surface functional groups in the presence of common electrolytes (NaCl, CaCl2, Na2SO4) and bovine serum albumin (BSA). It also examines the impact of different exposure orders, namely BSA + NaCl (adding them together), BSA → NaCl (adding BSA firstly and then NaCl), and NaCl → BSA (adding NaCl firstly and then BSA), on PSNPs aggregation. The presence of BSA decreased the critical coagulation concentration in NaCl (CCCNa+) of the non-modified PS-Bare from 222.17 to 142.81 mM (35.72%), but increased that of the carboxyl-modified PS-COOH from 157.34 to 160.03 mM (1.71%). This might be ascribed to the thicker absorbed layer of BSA onto the PS-Bare surface, known from Ohshima's soft particle theory. Their aggregation in CaCl2 was both increased because of Ca2+ bridging. Different from the monotonous effects of BSA on PS-Bare and PS-COOH, BSA initially facilitated PS-NH2 aggregation via patch-charge attraction, then inhibited it at higher salt levels through steric repulsion. Furthermore, exposure orders had no significant effect on PS-Bare and PS-COOH, but had a NaCl concentration-dependent impact on PS-NH2. At the low NaCl concentrations (10 and 100 mM), no obvious influence could be observed. While, at 300 mM NaCl, the high concentrations of BSA could not totally stabilize the salt-induced aggregates in NaCl → BSA, but could achieve it in the other two orders. These might be attributed to the electrical double layer compression by NaCl, "patch-charge" force and steric hindrance by BSA. These experimental findings shed light on the potential fate and transport of nanoparticles in aquatic environments.


Asunto(s)
Nanopartículas , Poliestirenos , Microplásticos , Cloruro de Sodio , Cloruro de Calcio , Electrólitos , Albúmina Sérica Bovina
17.
Chem Commun (Camb) ; 59(86): 12863-12866, 2023 Oct 26.
Artículo en Inglés | MEDLINE | ID: mdl-37815878

RESUMEN

Quinary RuRhPdPtAu high-entropy alloy nanoparticles (HEA-NPs) were prepared for the first time from a deep eutectic solvent by an electrochemical method. Owing to the benefits of high entropy and abundant surface active sites, the RuRhPdPtAu HEA-NPs exhibit outstanding electrocatalytic performance for the hydrogen evolution reaction.

18.
Mol Ther Nucleic Acids ; 34: 102028, 2023 Dec 12.
Artículo en Inglés | MEDLINE | ID: mdl-37744175

RESUMEN

Double-stranded DNA-specific cytidine deaminase (DddA) base editors hold great promise for applications in bio-medical research, medicine, and biotechnology. Strict sequence preference on spacing region presents a challenge for DddA editors to reach their full potential. To overcome this sequence-context constraint, we analyzed a protein dataset and identified a novel DddAtox homolog from Ruminococcus sp. AF17-6 (RsDddA). We engineered RsDddA for mitochondrial base editing in a mammalian cell line and demonstrated RsDddA-derived cytosine base editors (RsDdCBE) offered a broadened NC sequence compatibility and exhibited robust editing efficiency. Moreover, our results suggest the average frequencies of mitochondrial genome-wide off-target editing arising from RsDdCBE are comparable to canonical DdCBE and its variants.

19.
Ultrason Sonochem ; 100: 106600, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37741022

RESUMEN

Recently, bismuth (Bi)-based photocatalysts have been a well-deserved hotspot in the field of photocatalysis owning to their photoelectrochemical properties driven by the distortion of the Bi 6 s orbital, while their narrow band gap and poor quantum efficiency still restrict their application. With the development of ultrasonic technology, it is expected to become a broom to clear the application obstacles of Bi-based photocatalysts. The special forces and environmental conditions brought by ultrasonic irradiation play beneficial roles in the preparation, modification and performance releasement of Bi-based photocatalysts. In this review, the role and influencing factors of ultrasound in the preparation and modification of Bi-based photocatalysts were introduced. Crucially, the mechanism of the improving the performance for various types of Bi-based photocatalysts by ultrasound in the whole process of photocatalysis was deeply analyzed. Then, the application of ultrasonic synergistic Bi-based photocatalysts in contaminants treatment and energy conversion was briefly introduced. Finally, based on an unambiguous understanding of ultrasonic technology in assisting Bi-based photocatalysts, the future directions and possibilities for ultrasonic synergistic Bi-based photocatalysts are explored.

20.
Int J Mol Sci ; 24(16)2023 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-37628773

RESUMEN

Gene expression in eukaryotes begins with transcription in the nucleus, followed by the synthesis of messenger RNA (mRNA), which is then exported to the cytoplasm for its translation into proteins. Along with transcription and translation, mRNA export through the nuclear pore complex (NPC) is an essential regulatory step in eukaryotic gene expression. Multiple factors regulate mRNA export and hence gene expression. Interestingly, proteins from certain types of viruses interact with these factors in infected cells, and such an interaction interferes with the mRNA export of the host cell in favor of viral RNA export. Thus, these viruses hijack the host mRNA nuclear export mechanism, leading to a reduction in host gene expression and the downregulation of immune/antiviral responses. On the other hand, the viral mRNAs successfully evade the host surveillance system and are efficiently exported from the nucleus to the cytoplasm for translation, which enables the continuation of the virus life cycle. Here, we present this review to summarize the mechanisms by which viruses suppress host mRNA nuclear export during infection, as well as the key strategies that viruses use to facilitate their mRNA nuclear export. These studies have revealed new potential antivirals that may be used to inhibit viral mRNA transport and enhance host mRNA nuclear export, thereby promoting host gene expression and immune responses.


Asunto(s)
Virosis , Humanos , Transporte Activo de Núcleo Celular , Antivirales , Transporte de ARN , Eucariontes , ARN Mensajero/genética
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA