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1.
Int J Mol Sci ; 25(6)2024 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-38542280

RESUMEN

Cardiomyocyte survival is a critical contributing process of host adaptive responses to cardiovascular diseases (CVD). Cells of the cardiovascular endothelium have recently been reported to promote cardiomyocyte survival through exosome-loading cargos. Sphingosylphosphorylcholine (SPC), an intermediate metabolite of sphingolipids, mediates protection against myocardial infarction (MI). Nevertheless, the mechanism of SPC delivery by vascular endothelial cell (VEC)-derived exosomes (VEC-Exos) remains uncharacterized at the time of this writing. The present study utilized a mice model of ischemia/reperfusion (I/R) to demonstrate that the administration of exosomes via tail vein injection significantly diminished the severity of I/R-induced cardiac damage and prevented apoptosis of cardiomyocytes. Moreover, SPC was here identified as the primary mediator of the observed protective effects of VEC-Exos. In addition, within this investigation, in vitro experiments using cardiomyocytes showed that SPC counteracted myocardial I/R injury by activating the Parkin and nuclear receptor subfamily group A member 2/optineurin (NR4A2/OPTN) pathways, in turn resulting in increased levels of mitophagy within I/R-affected myocardium. The present study highlights the potential therapeutic effects of SPC-rich exosomes secreted by VECs on alleviating I/R-induced apoptosis in cardiomyocytes, thereby providing strong experimental evidence to support the application of SPC as a potential therapeutic target in the prevention and treatment of myocardial infarction.


Asunto(s)
Exosomas , Infarto del Miocardio , Daño por Reperfusión Miocárdica , Fosforilcolina/análogos & derivados , Esfingosina/análogos & derivados , Ratones , Animales , Daño por Reperfusión Miocárdica/metabolismo , Mitofagia , Miocitos Cardíacos/metabolismo , Infarto del Miocardio/tratamiento farmacológico , Infarto del Miocardio/metabolismo , Células Endoteliales/metabolismo , Exosomas/metabolismo , Apoptosis
2.
Mol Pharm ; 20(1): 606-615, 2023 01 02.
Artículo en Inglés | MEDLINE | ID: mdl-36398863

RESUMEN

As the most successful clinically approved photosensitizers, porphyrins have been extensively employed in the photodynamic therapy (PDT) of cancers. However, their poor water solubility, aggregation-induced self-quenching on ROS generation, and a low tolerance for a hypoxic condition usually result in unsatisfied therapeutic outcomes. Therefore, great efforts have been dedicated to improving the PDT efficacy of porphyrin-type photosensitizers in treating hypoxic tumors, including combination with additional active components or therapies, which can significantly complicate the therapeutic process. Herein, we report a novel water-soluble porphyrin with O-linked cationic side chains, which exhibits good water solubility, high photostability, and significantly enhanced ROS generation efficacy in both type-I and type-II photodynamic pathways. We have also found that the end charges of side chains can dramatically affect the ROS generation of the porphyrin. The cationic porphyrin exhibited high in vitro PDT efficacy with low IC50 values both in normoxia and hypoxia. Hence, during in vivo PDT study, the cationic porphyrin displayed highly effective tumor ablation capability. This study demonstrates the power of side-chain chemistry in tuning the photodynamic property of porphyrin, which offers a new effective strategy to enhance the anticancer performance of photosensitizers for fulfilling the increasing demands for cancer therapy in clinics.


Asunto(s)
Neoplasias , Fotoquimioterapia , Porfirinas , Humanos , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/química , Especies Reactivas de Oxígeno , Porfirinas/química , Agua , Neoplasias/tratamiento farmacológico , Hipoxia , Línea Celular Tumoral
3.
Chem Rev ; 121(22): 14031-14087, 2021 11 24.
Artículo en Inglés | MEDLINE | ID: mdl-34342989

RESUMEN

In nature, the self-assembly of sequence-specific biopolymers into hierarchical structures plays an essential role in the construction of functional biomaterials. To develop synthetic materials that can mimic and surpass the function of these natural counterparts, various sequence-defined bio- and biomimetic polymers have been developed and exploited as building blocks for hierarchical self-assembly. This review summarizes the recent advances in the molecular self-assembly of hierarchical nanomaterials based on peptoids (or poly-N-substituted glycines) and other sequence-defined synthetic polymers. Modern techniques to monitor the assembly mechanisms and characterize the physicochemical properties of these self-assembly systems are highlighted. In addition, discussions about their potential applications in biomedical sciences and renewable energy are also included. This review aims to highlight essential features of sequence-defined synthetic polymers (e.g., high stability and protein-like high-information content) and how these unique features enable the construction of robust biomimetic functional materials with high programmability and predictability, with an emphasis on peptoids and their self-assembled nanomaterials.


Asunto(s)
Materiales Biomiméticos , Nanoestructuras , Peptoides , Materiales Biomiméticos/química , Nanoestructuras/química , Peptoides/química , Polímeros
4.
Lung ; 201(1): 65-77, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36735045

RESUMEN

PURPOSE: Acute lung injury (ALI) with high rates of morbidity is often accompanied by the apoptosis in the type I alveolar epithelial cells (ATIs). Thus, the transdifferentiation of type II alveolar epithelial cells (ATIIs) into ATIs is crucial for the maintenance of alveolar epithelial functions. We aimed to elucidate the role of sesamin in the transdifferentiation of ATIIs to ATIs and the involvement of the TRPV1/AKT pathway. METHODS: In vivo, the mouse model of ALI was simulated by intraperitoneal and intratracheal injections of lipopolysaccharide (LPS), respectively. The protective effects of sesamin on ALI were investigated using the survival rate, lung/body weight ratio, histological analysis of lung with HE staining, and mRNA levels of inflammatory factors. Western blot analysis and immunofluorescence detection of ATIs marker AQP5 were used to evaluate the protective effect of sesamin on ATIs. Western blot, EdU, and qPCR analyses were applied to detect changes in apoptosis, proliferation, and transdifferentiation markers of ATII A549 cell lines. Small interfering RNA (siRNA) was used to detect the involvement and relationships between the sesamin receptors (ANXA1 and TRPV1) and the AKT pathway in transdifferentiation. RESULTS: Sesamin (200 mg/kg) significantly improved LPS-induced ALI and inhibited LPS-induced ATIs reduction. A low concentration of sesamin (20 µM) promoted the transdifferentiation of ATIIs to ATIs. Both ANXA1 and TRPV1 were involved in sesamin-promoted transdifferentiation, while the P-AKT (S473) level was down-regulated by TRPV1 siRNA. CONCLUSION: Sesamin may promote transdifferentiation of ATII to ATI to ultimately rescue ALI, with TRPV1/AKT pathway involved in this transdifferentiation. This study revealed a novel role of sesamin in promoting the transdifferentiation of ATIIs to ATIs, providing experimental supports for the potential targets of ALI therapy.


Asunto(s)
Lesión Pulmonar Aguda , Células Epiteliales Alveolares , Ratones , Animales , Células Epiteliales Alveolares/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Lipopolisacáridos , Transdiferenciación Celular , Lesión Pulmonar Aguda/patología , ARN Interferente Pequeño , Canales Catiónicos TRPV
5.
Molecules ; 28(10)2023 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-37241856

RESUMEN

Non-covalent interactions have been extensively used to fabricate nanoscale architectures in supramolecular chemistry. However, the biomimetic self-assembly of diverse nanostructures in aqueous solution with reversibility induced by different important biomolecules remains a challenge. Here, we report the synthesis and aqueous self-assembly of two chiral cationic porphyrins substituted with different types of side chains (branched or linear). Helical H-aggregates are induced by pyrophosphate (PPi) as indicated by circular dichroism (CD) measurement, while J-aggregates are formed with adenosine triphosphate (ATP) for the two porphyrins. By modifying the peripheral side chains from linear to a branched structure, more pronounced H- or J-type aggregation was promoted through the interactions between cationic porphyrins and the biological phosphate ions. Moreover, the phosphate-induced self-assembly of the cationic porphyrins is reversible in the presence of the enzyme alkaline phosphatase (ALP) and repeated addition of phosphates.


Asunto(s)
Adenosina Trifosfato , Difosfatos , Nanoestructuras , Porfirinas , Porfirinas/síntesis química , Cationes/síntesis química , Difosfatos/química , Adenosina Trifosfato/química , Fosfatasa Alcalina/química , Estructura Molecular , Simulación del Acoplamiento Molecular , Nanoestructuras/química , Electricidad Estática , Agua/química
6.
Acc Chem Res ; 54(1): 81-91, 2021 01 05.
Artículo en Inglés | MEDLINE | ID: mdl-33136361

RESUMEN

Natural organisms make a wide variety of exquisitely complex, nano-, micro-, and macroscale structured materials in an energy-efficient and highly reproducible manner. During these processes, the information-carrying biomolecules (e.g., proteins, peptides, and carbohydrates) enable (1) hierarchical organization to assemble scaffold materials and execute high-level functions and (2) exquisite control over inorganic materials synthesis, generating biominerals whose properties are optimized for their functions. Inspired by nature, significant efforts have been devoted to developing functional materials that can rival those natural molecules by mimicking in vivo functions using engineered proteins, peptides, DNAs, sequence-defined synthetic molecules (e.g., peptoids), and other biomimetic polymers. Among them, peptoids, a new type of synthetic mimetics of peptides and proteins, have received particular attention because they combine the merits of both synthetic polymers (e.g., high chemical stability and efficient synthesis) and biomolecules (e.g., sequence programmability and biocompatibility). The lack of both chirality and hydrogen bonds in their backbone results in a highly designable peptoid-based system with reduced structural complexity and side chain-chemistry-dominated properties.In this Account, we present our recent efforts in this field by programming amphiphilic peptoid sequences for (1) the controlled self-assembly into different hierarchically structured nanomaterials with favorable properties and (2) manipulating inorganic (nano)crystal nucleation, growth, and assembly into superstructures. First, we designed a series of amphiphilic peptoids with controlled side chain chemistries that self-assembled into 1D highly stiff and dynamic nanotubes, 2D membrane-mimetic nanosheets, hexagonally patterned nanoribbons, and 3D nanoflowers. These crystalline nanostructures exhibited sequence-dependent properties and showed promise for different applications. The corresponding peptoid self-assembly pathways and mechanisms were also investigated by leveraging in situ atomic force microscopy studies and molecular dynamics simulations, which showed precise sequence dependency. Second, inspired by peptide- and protein-controlled formation of hierarchical inorganic nanostructures in nature, we developed peptoid-based biomimetic approaches for controlled synthesis of inorganic materials (e.g., noble metals and calcite), in which we took advantage of the substantial side chain chemistry of peptoids and investigated the relationship between the peptoid sequences and the morphology and growth kinetics of inorganic materials. For example, to overcome the challenges (e.g., complexity of protein- and peptide-folding, poor thermal and chemical stabilities) facing the area of protein- and peptide-controlled synthesis of inorganic materials, we recently reported the design of sequence-defined peptoids for controlled synthesis of highly branched plasmonic gold particles. Moreover, we developed a rule of thumb for designing peptoids that predictively enabled the morphological evolution from spherical to coral-shaped gold nanoparticles (NPs). With this Account, we hope to stimulate the research interest of chemists and materials scientists and promote the predictive synthesis of functional and robust materials through the design of sequence-defined synthetic molecules.


Asunto(s)
Peptoides/química , Materiales Biomiméticos/química , Carbonato de Calcio/química , Cristalización , Oro/química , Nanopartículas del Metal/química , Microscopía de Fuerza Atómica , Nanoestructuras/química , Nanotubos/química
7.
Toxicol Appl Pharmacol ; 452: 116207, 2022 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-35995203

RESUMEN

Doxorubicin (DOX, C27H29NO11), is an anthracycline tumor chemotherapy drug, which has significant side effects on many organs including the heart. In recent years, mitochondrial dysfunction caused by DOX was identified as an important reason for cardiotoxic injury. Sphingosylphosphorylcholine (SPC) is essential for mitochondrial homeostasis in our previous report, however, its role in DOX-caused cardiomyopathy has remained elusive. Herein, DOX treated zebrafish embryos (90 µM) and adult fish (2.5 µM/g) were used to simulate DOX-induced cardiotoxic damage. Histopathological and ultrastructural observations showed that SPC (2.5 µM) significantly ameliorated DOX-induced pericardial edema, myocardial vacuolization and apoptosis. Furthermore, SPC (2.5 µM) can significantly inhibit DOX-induced apoptosis and promote cell proliferation in DOX treated H9c2 cells (1 µM), which is dependent on the restoration of mitochondrial homeostasis, including restored mitochondrial membrane potential, mitochondrial superoxide and ATP levels. We finally confirmed that SPC restored mitochondrial homeostasis through ameliorating DOX-induced excessive mitophagy. Mechanistically, SPC reduced calmodulin (CaM) levels and thus inhibiting Parkin activation and Parkin-dependent mitophagy. These results suggest that reducing the cardiotoxicity of chemotherapeutic drugs by targeting SPC may be a new solution to rescue chemotherapy injury.


Asunto(s)
Cardiotoxicidad , Mitofagia , Animales , Antibióticos Antineoplásicos/toxicidad , Apoptosis , Cardiotoxicidad/etiología , Doxorrubicina/efectos adversos , Mitocondrias , Miocitos Cardíacos , Fosforilcolina/análogos & derivados , Esfingosina/análogos & derivados , Ubiquitina-Proteína Ligasas/metabolismo , Pez Cebra/metabolismo
8.
Macromol Rapid Commun ; 43(4): e2100639, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-35038198

RESUMEN

It is reported herein the synthesis of a novel amphiphilic diblock peptoid bearing a terminal conjugated oligoaniline and its self-assembly into small-diameter (D ≈ 35 nm) crystalline nanotubes with high aspect ratios (>30). It is shown that both tetraaniline (TANI)-peptoid and bianiline (BANI)-peptoid triblock molecules self-assemble in solution to form rugged highly crystalline nanotubes that are very stable to protonic acid doping and de-doping processes. The similarity of the crystalline tubular structure of the nanotube assemblies revealed by electron microscopy imaging, and X-ray diffraction analysis of the nanotube assemblies of TANI-functionalized peptoids and nonfunctionalized peptoids showed that the peptoid is an efficient ordered structure directing motif for conjugated oligomers. Films of doped TANI-peptoid nanotubes has a dc conductivity of ca. 95 mS cm-1 , while the thin films of doped un-assembled TANI-peptoids show a factor of 5.6 lower conductivity, demonstrating impact of the favorable crystalline ordering of the assemblies on electrical transport. These results demonstrate that peptoid-directed supramolecular assembly of tethered π-conjugated oligo(aniline) exemplify a novel general strategy for creating rugged ordered and complex nanostructures that have useful electronic and optoelectronic properties.


Asunto(s)
Nanoestructuras , Nanotubos , Peptoides , Cristalografía por Rayos X , Microscopía Electrónica , Nanoestructuras/química , Nanotubos/química , Peptoides/química
9.
BMC Cardiovasc Disord ; 22(1): 413, 2022 09 16.
Artículo en Inglés | MEDLINE | ID: mdl-36114446

RESUMEN

BACKGROUND: Being physically active is important for cardiovascular health. This study aimed to examine the trend in adherence to the physical activity guidelines (PAG) for aerobic activity among US adults with a history of cardiovascular disease (CVD) and evaluated its association with cardiovascular risk factors. METHODS: We studied participants from the national health and nutrition examination survey 2007-08 to 2017-18. Regression models were used to evaluate the significance of the trend and the association between adherence to the PAG with cardiovascular risk factors. RESULTS: A total of 3638 participants were reported to have a history of CVD. The proportion of adherence to PAG significantly increased from 41.5% in 2007-08 to 54.3% in 2017-18. Males had a higher proportion of adherence compared to the females, while the trend in adherence was only significant in females. Adherence to the PAG was significantly associated with decreased levels of waist circumference, body mass index, hemoglobin A1c, and triglycerides. CONCLUSIONS: There is a significant increase in the proportion of adherence to the PAG among US adults with a history of CVD from 2007-08 to 2017-18, and adherence to the PAG was associated with improvement in cardiovascular risk factors.


Asunto(s)
Enfermedades Cardiovasculares , Adulto , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/prevención & control , Estudios Transversales , Ejercicio Físico , Femenino , Hemoglobina Glucada , Factores de Riesgo de Enfermedad Cardiaca , Humanos , Masculino , Encuestas Nutricionales , Factores de Riesgo , Triglicéridos
10.
BMC Pulm Med ; 22(1): 250, 2022 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-35752818

RESUMEN

BACKGROUND: This study was performed to develop and validate machine learning models for early detection of ventilator-associated pneumonia (VAP) 24 h before diagnosis, so that VAP patients can receive early intervention and reduce the occurrence of complications. PATIENTS AND METHODS: This study was based on the MIMIC-III dataset, which was a retrospective cohort. The random forest algorithm was applied to construct a base classifier, and the area under the receiver operating characteristic curve (AUC), sensitivity and specificity of the prediction model were evaluated. Furthermore, We also compare the performance of Clinical Pulmonary Infection Score (CPIS)-based model (threshold value ≥ 3) using the same training and test data sets. RESULTS: In total, 38,515 ventilation sessions occurred in 61,532 ICU admissions. VAP occurred in 212 of these sessions. We incorporated 42 VAP risk factors at admission and routinely measured the vital characteristics and laboratory results. Five-fold cross-validation was performed to evaluate the model performance, and the model achieved an AUC of 84% in the validation, 74% sensitivity and 71% specificity 24 h after intubation. The AUC of our VAP machine learning model is nearly 25% higher than the CPIS model, and the sensitivity and specificity were also improved by almost 14% and 15%, respectively. CONCLUSIONS: We developed and internally validated an automated model for VAP prediction using the MIMIC-III cohort. The VAP prediction model achieved high performance based on its AUC, sensitivity and specificity, and its performance was superior to that of the CPIS model. External validation and prospective interventional or outcome studies using this prediction model are envisioned as future work.


Asunto(s)
Neumonía Asociada al Ventilador , Cuidados Críticos , Humanos , Unidades de Cuidados Intensivos , Aprendizaje Automático , Neumonía Asociada al Ventilador/diagnóstico , Neumonía Asociada al Ventilador/epidemiología , Estudios Prospectivos , Estudios Retrospectivos
11.
Proc Natl Acad Sci U S A ; 116(31): 15386-15391, 2019 07 30.
Artículo en Inglés | MEDLINE | ID: mdl-31308243

RESUMEN

We report a conjugated polyelectrolyte fluorescence-based biosensor P-C-3 and a general methodology to evaluate spectral shape recognition to identify biomolecules using artificial intelligence. By using well-defined analytes, we demonstrate that the fluorescence spectral shape of P-C-3 is sensitive to minor structural changes and exhibits distinct signature patterns for different analytes. A method was also developed to select useful features to reduce computational complexity and prevent overfitting of the data. It was found that the normalized intensity of 3 to 5 selected wavelengths was sufficient for the fluorescence biosensor to classify 13 distinct nucleotides and distinguish as little as single base substitutions at distinct positions in the primary sequence of oligonucleotides rapidly with nearly 100% classification accuracy. Photophysical studies led to a model to explain the mechanism of these fluorescence spectral shape changes, which provides theoretical support for applying this method in complicated biological systems. Using the feature selection algorithm to measure the relative intensity of a few selected wavelengths significantly reduces measurement time, demonstrating the potential for fluorescence spectrum shape analysis in high-throughput and high-content screening.


Asunto(s)
Nucleótidos/química , Análisis Discriminante , Luz , Espectrometría de Fluorescencia , Factores de Tiempo
12.
Sensors (Basel) ; 22(9)2022 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-35590973

RESUMEN

The difficulty of atmospheric correction based on a radiative transfer model lies in the acquisition of synchronized atmospheric parameters, especially the aerosol optical depth (AOD). At the moment, there is no fully automatic and high-efficiency atmospheric correction method to make full use of the advantages of geostationary meteorological satellites in large-scale and efficient atmospheric monitoring. Therefore, a QUantitative and Automatic Atmospheric Correction (QUAAC) method is proposed which can efficiently correct high-spatial-resolution (HSR) satellite images. QUAAC uses the atmospheric aerosol products of geostationary satellites to match the synchronized AOD according to the temporal and spatial information of HSR satellite images. This method solves the problem that the AOD is difficult to obtain or the accuracy is not high enough to meet the demand of atmospheric correction. By using the obtained atmospheric parameters, atmospheric correction is performed to obtain the surface reflectance (SR). The whole process can achieve fully automatic operation without manual intervention. After QUAAC applied to Gaofen-2 (GF-2) HSR satellite and Himawari-8 (H-8) geostationary satellite, the results show that the effect of QUAAC correction is slightly better than that of the Fast Line-of-sight Atmospheric Analysis of Spectral Hypercubes (FLAASH) correction, and the QUAAC-corrected surface spectral curves have good coherence to that of the synchronously measured by field experiments.

13.
Molecules ; 27(7)2022 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-35408574

RESUMEN

Momordica charantia L., a member of the Curcubitaceae family, has traditionally been used as herbal medicine and as a vegetable. Functional ingredients of M. charantia play important roles in body health and human nutrition, which can be used directly or indirectly in treating or preventing hyperglycemia-related chronic diseases in humans. The hypoglycemic effects of M. charantia have been known for years. In this paper, the research progress of M. charantia phytobioactives and their hypoglycemic effects and related mechanisms, especially relating to diabetes mellitus, has been reviewed. Moreover, the clinical application of M. charantia in treating diabetes mellitus is also discussed, hoping to broaden the application of M. charantia as functional food.


Asunto(s)
Diabetes Mellitus Tipo 2 , Momordica charantia , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Humanos , Hipoglucemiantes/farmacología , Hipoglucemiantes/uso terapéutico , Fitoterapia , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico
14.
Hum Brain Mapp ; 42(11): 3440-3449, 2021 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-33830581

RESUMEN

The aberrant thalamocortical pathways of epilepsy have been detected recently, while its underlying effects on epilepsy are still not well understood. Exploring pathoglytic changes in two important thalamocortical pathways, that is, the basal ganglia (BG)-thalamocortical and the cerebellum-thalamocortical pathways, in people with idiopathic generalized epilepsy (IGE), could deepen our understanding on the pathological mechanism of this disease. These two pathways were reconstructed and investigated in this study by combining diffusion and functional MRI. Both pathways showed connectivity changes with the perception and cognition systems in patients. Consistent functional connectivity (FC) changes were observed mainly in perception regions, revealing the aberrant integration of sensorimotor and visual information in IGE. The pathway-specific FC alterations in high-order regions give neuroimaging evidence of the neural mechanisms of cognitive impairment and epileptic activities in IGE. Abnormal functional and structural integration of cerebellum, basal ganglia and thalamus could result in an imbalance of inhibition and excitability in brain systems of IGE. This study located the regulated cortical regions of BG and cerebellum which been affected in IGE, established possible links between the neuroimaging findings and epileptic symptoms, and enriched the understanding of the regulatory effects of BG and cerebellum on epilepsy.


Asunto(s)
Ganglios Basales/fisiopatología , Cerebelo/fisiopatología , Corteza Cerebral/fisiopatología , Conectoma , Epilepsia Generalizada/fisiopatología , Red Nerviosa/fisiopatología , Tálamo/fisiopatología , Adulto , Ganglios Basales/diagnóstico por imagen , Cerebelo/diagnóstico por imagen , Corteza Cerebral/diagnóstico por imagen , Epilepsia Generalizada/diagnóstico por imagen , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Red Nerviosa/diagnóstico por imagen , Vías Nerviosas/diagnóstico por imagen , Vías Nerviosas/fisiopatología , Tálamo/diagnóstico por imagen , Adulto Joven
15.
Connect Tissue Res ; 62(3): 337-349, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-32180463

RESUMEN

Purpose: Reactive oxygen species (ROS) are related to compression stress-induced nucleus pulposus (NP) cell autophagy, but the specific mechanism is unknown in compression stress-induced intervertebral disc degeneration (IVDD). Here, we discuss the specific molecular mechanism and explore whether ROS scavengers could be employed as specific drugs to inhibit compression stress-induced IVDD.Methods: Rat NP cells were exposed to 1.0 MPa compression and pretreatment with the ROS scavenger N-acetylcysteine (NAC) or the JNK-selective inhibitor SP600125 not. Intracellular ROS production was monitored by confocal microscopy. Autophagy was detected by observing the NP cell ultrastructural features using TEM and examining autophagic vacuoles by flow cytometry. The levels of autophagy-associated molecules, the JNK pathway and the PI3K/AKT/mTOR pathway were analyzed by western blotting.Results: Compression-mediated autophagy in rat NP cells was implicated in ROS generation. The ROS scavenger NAC could protect compression-induced NP cell injures by inhibiting ROS production. And SP600125, a JNK inhibitor, attenuated compression-induced NP cell autophagy. Additionally, this is the first report showing that compression induces autophagy in rat NP cells by impeding the compression-induced ROS dependent PI3K/AKT/mTOR pathway and the ROS independent activation of JNK pathway. And the involvement of JNK pathway was in different mechanism of action that when inhibited leaded to increased cell death, increased generation of ROS but decreased autophagy.Conclusions: These results show a new regulatory mechanism involving ROS-mediated autophagy in rat NP cells, which may provide ideas for drug development to improve compression stress-induced IVDD and help avoid eventual surgical treatment of IVD herniation.


Asunto(s)
Degeneración del Disco Intervertebral , Núcleo Pulposo , Animales , Apoptosis , Autofagia , Degeneración del Disco Intervertebral/tratamiento farmacológico , Degeneración del Disco Intervertebral/metabolismo , Sistema de Señalización de MAP Quinasas , Núcleo Pulposo/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas , Especies Reactivas de Oxígeno/metabolismo , Serina-Treonina Quinasas TOR/metabolismo
16.
J Phys Chem A ; 125(18): 3863-3873, 2021 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-33945279

RESUMEN

This paper reports a photophysical investigation of a series of phenylene ethynylene oligomers (OPE) that are end-substituted with a 1,8-naphthalene imide (NI) acceptor. The NI acceptor is attached to the terminus of the OPEs via an ethynylene (-C≡C-) unit that is linked at the 4-position of the NI unit. A series of three oligomers is investigated, OPE1-NI, OPE3-NI, and OPE5-NI, which contain 1, 3, and 5 phenylene ethynylene repeat units, respectively. The properties of the OPEn-NI series are compared to a corresponding set of unsubstituted OPEs, OPE3 and OPE5, which contain 3 and 5 phenylene ethynylene repeats, respectively. The photophysics of all the compounds are interrogated using a variety of techniques including steady-state absorption, steady-state fluorescence, two-photon absorption, time-resolved fluorescence, and transient absorption spectroscopy on femtosecond-to-microsecond time scales. The effect of solvent polarity on the properties of the oligomers is examined. The results show that the NI-substituted oligomers feature a lowest charge transfer (CT) excited state, where the OPE segment acts as the donor and the NI moiety is the acceptor (OPEn•+-NI•-). The absorption spectra in one-photon and two-photon exhibit a clear manifold of absorption features that can be attributed to direct CT absorption. In moderately polar solvents, the emission is dominated by a broad, solvatochromic band that is due to radiative decay from the CT excited state. Ultrafast transient absorption provides evidence for initial population of a locally excited state (LE) which in moderately polar solvents rapidly (∼1 ps) evolves into the CT excited state. The structure, spectroscopy, and dynamics of the CT state are qualitatively similar for OPE3-NI and OPE5-NI, suggesting that delocalization in the OPE segment does not have much effect on the structure or energetics of the CT excited state.

17.
BMC Anesthesiol ; 21(1): 26, 2021 01 22.
Artículo en Inglés | MEDLINE | ID: mdl-33482737

RESUMEN

BACKGROUND: Soluble CD40 ligand (sCD40L) exhibits proinflammatory and procoagulant effects. Recent data indicated that sCD40L plays a significant role in septic patients. The aim of the present study was to determine sCD40L changes in surgical patients without sepsis (SWS) and surgical sepsis patients (SS) during the first 3 days after intensive care unit (ICU) admission and to observe the association between sCD40L and mortality. METHODS: Time changes in sCD40L levels were assessed for 3 days after ICU admission in 49 patients with SS and compared with those in 19 SWS patients. Serum sCD40L concentration was detected by ELISA. Survival at 28 days served as the endpoint. RESULTS: SS had significantly higher sCD40L levels than SWS and control patients. We observed an association between sCD40L levels ≥1028.75 pg/mL at day 2 and 28-day mortality (odds ratio = 7.888; 95% confidence interval = 1.758 to 35.395; P = 0.007). We could not discover any significant differences in sex, presence of septic shock, site of infection, length of stay in the ICU, PaO2/FiO2 ratio, incidence of AKI, ARDS, or type of surgery between nonsurvivors and survivors. CONCLUSIONS: Septic patients show persistently higher circulating sCD40L levels in the first 3 days after ICU admission, and serum sCD40L levels are associated with the mortality of patients with sepsis. Thus, serum sCD40L may be used as a reliable biomarker and therapeutic target in sepsis.


Asunto(s)
Biomarcadores/sangre , Ligando de CD40/sangre , Sepsis/sangre , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos
18.
Molecules ; 26(12)2021 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-34203004

RESUMEN

Green tea and its bioactive components, especially polyphenols, possess many health-promoting and disease-preventing benefits, especially anti-inflammatory, antioxidant, anticancer, and metabolic modulation effects with multi-target modes of action. However, the effect of tea polyphenols on immune function has not been well studied. Moreover, the underlying cellular and molecular mechanisms mediating immunoregulation are not well understood. This review summarizes the recent studies on the immune-potentiating effects and corresponding mechanisms of tea polyphenols, especially the main components of (-)-epigallocatechin-3-gallate (EGCG) and (-)-epicatechin-3-gallate (ECG). In addition, the benefits towards immune-related diseases, such as autoimmune diseases, cutaneous-related immune diseases, and obesity-related immune diseases, have been discussed.


Asunto(s)
Antioxidantes/farmacología , Inmunidad/efectos de los fármacos , Factores Inmunológicos/farmacología , Polifenoles/farmacología , Té/química , Animales , Antioxidantes/química , Productos Biológicos/química , Productos Biológicos/farmacología , Catequina/análogos & derivados , Catequina/química , Catequina/farmacología , Flavonoides/química , Flavonoides/farmacología , Humanos , Factores Inmunológicos/química , Polifenoles/química
19.
Water Sci Technol ; 84(3): 596-608, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-34388121

RESUMEN

The iron oxychloride/pillared montmorillonite (FeOCl/MMT) catalyst was prepared by wet impregnation method and solid melting method. Various characterization techniques were used to analyze the microscopic morphology and structure of a series of catalysts. Moreover, the catalysts were used to treat magenta-simulated dye wastewater through catalytic wet peroxide oxidation (CWPO) degradation. The magenta removal rate and chemical oxygen demand (COD) removal rate of the magenta-simulated dye wastewater were used to evaluate the catalytic performance of the catalyst, and the optimal catalyst preparation conditions were selected. The results showed that the solid melting method was more favorable to the preparation of the catalyst, and the COD removal rate of wastewater can reach 70.8% when the FeOCl load was 3%. Moreover, 96.2% of the magenta in the solution was removed. The COD removal rate of the magenta wastewater decreased by only 12.4% after the catalyst was repeatedly used six times, indicating that the catalyst has good activity and stability. The Fermi equation can simulate the reaction process of the catalyst treating magenta wastewater at high temperature.


Asunto(s)
Peróxidos , Aguas Residuales , Bentonita , Catálisis , Peróxido de Hidrógeno , Oxidación-Reducción , Colorantes de Rosanilina
20.
J Cell Mol Med ; 24(10): 5850-5864, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-32281308

RESUMEN

The current research aimed to explore the possible relationship between PINK1/PARKIN-mediated mitophagy and the compression-induced senescence of nucleus pulposus cells (NPCs). Therefore, the stages of senescence in NPCs were measured under compression lasting 0, 24 and 48 hours. The mitophagy-related markers, autophagosomes and mitochondrial membrane potential were tested to determine the levels of PINK1/PARKIN-mediated mitophagy under compression. The PINK1 and PARKIN levels were also measured by immunohistochemistry of human and rat intervertebral disc (IVD) tissues taken at different degenerative stages. A specific mitophagy inhibitor, cyclosporine A (CSA) and a constructed PINK1-shRNA were used to explore the relationship between mitophagy and senescence by down-regulating the PINK1/PARKIN-mediated mitophagy levels. Our results indicated that compression significantly enhanced the senescence of NPCs in a time-dependent manner. Also, PINK1/PARKIN-mediated mitophagy was found to be activated by the extended duration of compression on NPCs as well as the increased degenerative stages of IVD tissues. After inhibition of PINK1/PARKIN-mediated mitophagy by CSA and PINK1-shRNA, the senescence of NPCs induced by compression was strongly rescued. Hence, the excessive degradation of mitochondria in NPCs by mitophagy under continuous compression may accelerate the senescence of NPCs. Regulating PINK1/PARKIN-mediated mitophagy might be a potential therapeutic treatment for IVD degeneration.


Asunto(s)
Senescencia Celular , Fuerza Compresiva , Mitofagia , Núcleo Pulposo/patología , Proteínas Quinasas/metabolismo , Transducción de Señal , Ubiquitina-Proteína Ligasas/metabolismo , Animales , Senescencia Celular/efectos de los fármacos , Ciclosporina/farmacología , Regulación hacia Abajo/efectos de los fármacos , Humanos , Masculino , Mitofagia/efectos de los fármacos , Núcleo Pulposo/ultraestructura , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacos , Regulación hacia Arriba/efectos de los fármacos
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