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1.
Nature ; 618(7966): 687-697, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37344649

RESUMEN

Light and sound are the most ubiquitous forms of waves, associated with a variety of phenomena and physical effects such as rainbows and echoes. Light and sound, both categorized as classical waves, have lately been brought into unexpected connections with exotic topological phases of matter. We are currently witnessing the onset of a second wave of active research into this topic. The past decade has been marked by fundamental advances comprising two-dimensional quantum Hall insulators and quantum spin and valley Hall insulators, whose topological properties are characterized using linear band topology. Here, going beyond these conventional topological systems, we focus on the latest frontiers, including non-Hermitian, nonlinear and non-Abelian topology as well as topological defects, for which the characterization of the topological features goes beyond the standard band-topology language. In addition to an overview of the current state of the art, we also survey future research directions for valuable applications.

2.
FASEB J ; 38(13): e23780, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-38948938

RESUMEN

Aerobic training (AT), an effective form of cardiac rehabilitation, has been shown to be beneficial for cardiac repair and remodeling after myocardial infarction (MI). The p300/CBP-associated factor (PCAF) is one of the most important lysine acetyltransferases and is involved in various biological processes. However, the role of PCAF in AT and AT-mediated cardiac remodeling post-MI has not been determined. Here, we found that the PCAF protein level was significantly increased after MI, while AT blocked the increase in PCAF. AT markedly improved cardiac remodeling in mice after MI by reducing endoplasmic reticulum stress (ERS). In vivo, similar to AT, pharmacological inhibition of PCAF by Embelin improved cardiac recovery and attenuated ERS in MI mice. Furthermore, we observed that both IGF-1, a simulated exercise environment, and Embelin protected from H2O2-induced cardiomyocyte injury, while PCAF overexpression by viruses or the sirtuin inhibitor nicotinamide eliminated the protective effect of IGF-1 in H9C2 cells. Thus, our data indicate that maintaining low PCAF levels plays an essential role in AT-mediated cardiac protection, and PCAF inhibition represents a promising therapeutic target for attenuating cardiac remodeling after MI.


Asunto(s)
Infarto del Miocardio , Condicionamiento Físico Animal , Remodelación Ventricular , Factores de Transcripción p300-CBP , Animales , Factores de Transcripción p300-CBP/metabolismo , Factores de Transcripción p300-CBP/antagonistas & inhibidores , Infarto del Miocardio/metabolismo , Infarto del Miocardio/patología , Ratones , Remodelación Ventricular/efectos de los fármacos , Remodelación Ventricular/fisiología , Masculino , Ratones Endogámicos C57BL , Miocitos Cardíacos/metabolismo , Estrés del Retículo Endoplásmico/efectos de los fármacos
3.
J Immunol ; 211(5): 836-843, 2023 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-37466391

RESUMEN

Our previous studies identified a population of stem cell-like proliferating myeloid cells within inflamed tissues that could serve as a reservoir for tissue macrophages to adopt different activation states depending on the microenvironment. By lineage-tracing cells derived from CX3CR1+ precursors in mice during infection and profiling by single-cell RNA sequencing, in this study, we identify a cluster of BIRC5+ myeloid cells that expanded in the liver during chronic infection with either the parasite Schistosoma mansoni or the bacterial pathogen Staphylococcus aureus. In the absence of tissue-damaging toxins, S. aureus infection does not elicit these BIRC5+ cells. Moreover, deletion of BIRC5 from CX3CR1-expressing cells results in improved survival during S. aureus infection. Hence the combination of single-cell RNA sequencing and genetic fate-mapping CX3CR1+ cells revealed a toxin-dependent pathogenic role for BIRC5 in myeloid cells during S. aureus infection.


Asunto(s)
Infecciones Estafilocócicas , Staphylococcus aureus , Ratones , Animales , Células Mieloides/patología , Análisis de la Célula Individual , Infecciones Estafilocócicas/microbiología
4.
Proc Natl Acad Sci U S A ; 119(31): e2123017119, 2022 08 02.
Artículo en Inglés | MEDLINE | ID: mdl-35881802

RESUMEN

Staphylococcus aureus is an opportunistic pathogen and chief among bloodstream-infecting bacteria. S. aureus produces an array of human-specific virulence factors that may contribute to immune suppression. Here, we defined the response of primary human phagocytes following infection with S. aureus using RNA-sequencing (RNA-Seq). We found that the overall transcriptional response to S. aureus was weak both in the number of genes and in the magnitude of response. Using an ex vivo bacteremia model with fresh human blood, we uncovered that infection with S. aureus resulted in the down-regulation of genes related to innate immune response and cytokine and chemokine signaling. This muted transcriptional response was conserved across diverse S. aureus clones but absent in blood exposed to heat-killed S. aureus or blood infected with the less virulent staphylococcal species Staphylococcus epidermidis. Notably, this signature was also present in patients with S. aureus bacteremia. We identified the master regulator S. aureus exoprotein expression (SaeRS) and the SaeRS-regulated pore-forming toxins as key mediators of the transcriptional suppression. The S. aureus-mediated suppression of chemokine and cytokine transcription was reflected by circulating protein levels in the plasma. Wild-type S. aureus elicited a soluble milieu that was restrictive in the recruitment of human neutrophils compared with strains lacking saeRS. Thus, S. aureus blunts the inflammatory response resulting in impaired neutrophil recruitment, which could promote the survival of the pathogen during invasive infection.


Asunto(s)
Interacciones Huésped-Patógeno , Neutrófilos , Infecciones Estafilocócicas , Staphylococcus aureus , Bacteriemia/inmunología , Bacteriemia/microbiología , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Citocinas/metabolismo , Regulación Bacteriana de la Expresión Génica , Interacciones Huésped-Patógeno/inmunología , Humanos , Neutrófilos/inmunología , Neutrófilos/microbiología , Proteínas Citotóxicas Formadoras de Poros/genética , Infecciones Estafilocócicas/sangre , Infecciones Estafilocócicas/inmunología , Infecciones Estafilocócicas/microbiología , Staphylococcus aureus/genética , Staphylococcus aureus/patogenicidad , Staphylococcus epidermidis/patogenicidad , Factores de Transcripción/genética , Factores de Transcripción/metabolismo
5.
Nano Lett ; 24(18): 5521-5528, 2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38662651

RESUMEN

Exploring multiple states based on the domain wall (DW) position has garnered increased attention for in-memory computing applications, particularly focusing on the utilization of spin-orbit torque (SOT) to drive DW motion. However, devices relying on the DW position require efficient DW pinning. Here, we achieve granular magnetization switching by incorporating an HfOx insertion layer between the Co/Ti interface. This corresponds to a transition in the switching model from the DW motion to DW nucleation. Compared to the conventional Pt/Co/Ti structure, incorporation of the HfOx layer results in an enhanced SOT efficiency and a lower switching current density. We also realized stable multistate storage and synaptic plasticity by applying pulse current in the Pt/Co/HfOx/Ti device. The simulation of artificial neural networks (ANN) based on the device can perform digital recognition tasks with an accuracy rate of 91%. These results identify that DW nucleation with a Pt/Co/HfOx/Ti based device has potential applications in multistate storage and ANN.

6.
Curr Issues Mol Biol ; 46(3): 2701-2712, 2024 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-38534786

RESUMEN

Inflammation and collagen-degrading enzymes' overexpression promote collagen decomposition, which affects the structural integrity of the extracellular matrix. The polysaccharide and peptide extracts of the green alga Caulerpa microphysa (C. microphysa) have been proven to have anti-inflammatory, wound healing, and antioxidant effects in vivo and in vitro. However, the biological properties of the non-water-soluble components of C. microphysa are still unknown. In the present study, we demonstrated the higher effective anti-inflammatory functions of C. microphysa ethyl acetate (EA) extract than water extract up to 16-30% in LPS-induced HaCaT cells, including reducing the production of interleukin (IL)-1ß, IL-6, IL-8, and tumor necrosis factor-α (TNF-α). Furthermore, the excellent collagen homeostasis effects from C. microphysa were proven by suppressing the matrix metalloproteinase-1 (MMP-1) secretion, enhancing type 1 procollagen and collagen expressions dose-dependently in WS1 cells. Moreover, using UHPLC-QTOF-MS analysis, four terpenoids, siphonaxanthin, caulerpenyne, caulerpal A, and caulerpal B, were identified and may be involved in the superior collagen homeostasis and anti-inflammatory effects of the C. microphysa EA extract.

7.
Eur J Neurosci ; 59(8): 2016-2028, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38382896

RESUMEN

The aim of this work was to analyse the effect of tandem repetitions in exon III of the DRD4 gene on the features of human decision-making in a model of choosing tourist attractions by adult residents of China. The study included 380 subjects: 162 (42.6%) men and 218 (57.4%) women. The mean age of the subjects was 31.7 ± 3.32 years. As a result of the survey of subjects, 5 groups of motivations for choosing tourist attractions were identified, and the frequency of their use, including the identified combinations, was determined. Using the genotyping method, the frequency of DRD4 subtypes among the subjects was determined, and their relationship with the indicated attraction selection groups was studied. It has been established that there is a significant dependence of the frequency of choosing the attractors 'relaxation', 'desire for novelty' and 'self-realization' and their combinations on the frequency of occurrence of the DRD4 2R, 4R and 5R+ subtypes in the study groups. A conclusion was made about the possible mechanism of the influence of manifestations of DRD4 subtypes on the choice of tourist attractors by implementing the neurophysiological influence of the genome on reducing the sensitivity of brain receptors to dopamine, which stimulates behaviours that compensate for the need for additional emotional influences. This work complements the existing knowledge about the impact of human innate properties on the characteristics of his behaviour and possible patterns of influence of human genotype variability on decision-making and suggests further possible directions of research in this area.


Asunto(s)
Repeticiones de Minisatélite , Receptores de Dopamina D4 , Masculino , Adulto , Humanos , Femenino , Receptores de Dopamina D4/genética , Genotipo , Exones , Emociones
8.
Biochem Biophys Res Commun ; 725: 150260, 2024 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-38878760

RESUMEN

This study introduces an innovative brain-targeted drug delivery system, RVG-Exo/CBD, utilizing rabies virus glycoprotein (RVG)-engineered exosomes for encapsulating cannabidiol (CBD). The novel delivery system was meticulously characterized, confirming the maintenance of exosomal integrity, size, and successful drug encapsulation with a high drug loading rate of 83.0 %. Evaluation of the RVG-Exo/CBD's brain-targeting capability demonstrated superior distribution and retention in brain tissue compared to unmodified exosomes, primarily validated through in vivo fluorescence imaging. The efficacy of this delivery system was assessed using a behavioral sensitization model in mice, where RVG-Exo/CBD notably suppressed methamphetamine-induced hyperactivity more effectively than CBD alone, indicating a reduction in effective dose and enhanced bioavailability. Overall, the RVG-Exo/CBD system emerges as a promising strategy for enhancing the therapeutic efficacy and safety of CBD, particularly for neurological applications, highlighting its potential for addressing the limitations associated with traditional CBD administration in clinical settings.


Asunto(s)
Encéfalo , Cannabidiol , Cannabidiol/administración & dosificación , Cannabidiol/química , Cannabidiol/farmacología , Animales , Encéfalo/metabolismo , Encéfalo/efectos de los fármacos , Ratones , Masculino , Glicoproteínas/química , Glicoproteínas/metabolismo , Glicoproteínas/administración & dosificación , Sistemas de Liberación de Medicamentos/métodos , Fragmentos de Péptidos , Proteínas Virales
9.
Biochem Biophys Res Commun ; 710: 149883, 2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38588611

RESUMEN

Congenital heart diseases are the most common birth defects around the world. Emerging evidence suggests that mitochondrial homeostasis is required for normal heart development. In mitochondria, a series of molecular chaperones including heat shock protein 60 (HSP60) are engaged in assisting the import and folding of mitochondrial proteins. However, it remains largely obscure whether and how these mitochondrial chaperones regulate cardiac development. Here, we generated a cardiac-specific Hspd1 deletion mouse model by αMHC-Cre and investigated the role of HSP60 in cardiac development. We observed that deletion of HSP60 in embryonic cardiomyocytes resulted in abnormal heart development and embryonic lethality, characterized by reduced cardiac cell proliferation and thinner ventricular walls, highlighting an essential role of cardiac HSP60 in embryonic heart development and survival. Our results also demonstrated that HSP60 deficiency caused significant downregulation of mitochondrial ETC subunits and induced mitochondrial stress. Analysis of gene expression revealed that P21 that negatively regulates cell proliferation is significantly upregulated in HSP60 knockout hearts. Moreover, HSP60 deficiency induced activation of eIF2α-ATF4 pathway, further indicating the underlying mitochondrial stress in cardiomyocytes after HSP60 deletion. Taken together, our study demonstrated that regular function of mitochondrial chaperones is pivotal for maintaining normal mitochondrial homeostasis and embryonic heart development.


Asunto(s)
Chaperonina 60 , Cardiopatías Congénitas , Animales , Ratones , Chaperonina 60/genética , Chaperonina 60/metabolismo , Cardiopatías Congénitas/metabolismo , Mitocondrias/metabolismo , Proteínas Mitocondriales/metabolismo , Chaperonas Moleculares/genética , Chaperonas Moleculares/metabolismo , Miocitos Cardíacos/metabolismo
10.
Chembiochem ; 25(3): e202300678, 2024 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-38015421

RESUMEN

Using myoglobin (Mb) as a model protein, we herein developed a facial approach to modifying the heme active site. A cavity was first generated in the heme distal site by F46 C mutation, and the thiol group of Cys46 was then used for covalently linked to exogenous ligands, 1H-1,2,4-triazole-3-thiol and 1-(4-hydroxyphenyl)-1H-pyrrole-2,5-dione. The engineered proteins, termed F46C-triazole Mb and F46C-phenol Mb, respectively, were characterized by X-ray crystallography, spectroscopic and stopped-flow kinetic studies. The results showed that both the heme coordination state and the protein function such as H2 O2 activation and peroxidase activity could be efficiently regulated, which suggests that this approach might be generally applied to the design of functional heme proteins.


Asunto(s)
Hemo , Mioglobina , Mioglobina/química , Mioglobina/genética , Mioglobina/metabolismo , Dominio Catalítico , Hemo/química , Cinética , Conformación Proteica , Compuestos de Sulfhidrilo
11.
Basic Res Cardiol ; 119(1): 57-74, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38151579

RESUMEN

Cardiac sympathetic overactivation is a critical driver in the progression of acute myocardial infarction (AMI). The left middle cervical ganglion (LMCG) is an important extracardiac sympathetic ganglion. However, the regulatory effects of LMCG on AMI have not yet been fully documented. In the present study, we detected that the LMCG was innervated by abundant sympathetic components and exerted an excitatory effect on the cardiac sympathetic nervous system in response to stimulation. In canine models of AMI, targeted ablation of LMCG reduced the sympathetic indexes of heart rate variability and serum norepinephrine, resulting in suppressed cardiac sympathetic activity. Moreover, LMCG ablation could improve ventricular electrophysiological stability, evidenced by the prolonged ventricular effective refractory period, elevated action potential duration, increased ventricular fibrillation threshold, and enhanced connexin43 expression, consequently showing antiarrhythmic effects. Additionally, compared with the control group, myocardial infarction size, circulating cardiac troponin I, and myocardial apoptosis were significantly reduced, accompanied by preserved cardiac function in canines subjected to LMCG ablation. Finally, we performed the left stellate ganglion (LSG) ablation and compared its effects with LMCG destruction. The results indicated that LMCG ablation prevented ventricular electrophysiological instability, cardiac sympathetic activation, and AMI-induced ventricular arrhythmias with similar efficiency as LSG denervation. In conclusion, this study demonstrated that LMCG ablation suppressed cardiac sympathetic activity, stabilized ventricular electrophysiological properties and mitigated cardiomyocyte death, resultantly preventing ischemia-induced ventricular arrhythmias, myocardial injury, and cardiac dysfunction. Neuromodulation therapy targeting LMCG represented a promising strategy for the treatment of AMI.


Asunto(s)
Infarto del Miocardio , Animales , Perros , Arritmias Cardíacas , Corazón/inervación , Fibrilación Ventricular/etiología , Fibrilación Ventricular/prevención & control , Ganglios Simpáticos/metabolismo
12.
Circ Res ; 130(10): 1586-1600, 2022 05 13.
Artículo en Inglés | MEDLINE | ID: mdl-35437018

RESUMEN

BACKGROUND: Pathological cardiac hypertrophy is one of the leading causes of heart failure with highly complicated pathogeneses. The E3 ligase TRIM16 (tripartite motif-containing protein 16) has been recognized as a pivotal regulator to control cell survival, immune response, and oxidativestress. However, the role of Trim16 in cardiac hypertrophy is unknown. METHODS: We generated cardiac-specific knockout mice and adeno-associated virus serotype 9-Trim16 mice to evaluate the function of Trim16 in pathological myocardial hypertrophy. The direct effect of TRIM16 on cardiomyocyte enlargement was examined using an adenovirus system. Furthermore, we combined RNA-sequencing and interactome analysis that was followed by multiple molecular biological methodologies to identify the direct target and corresponding molecular events contributing to TRIM16 function. RESULTS: We found an intimate correlation of Trim16 expression with hypertrophy-related heart failure in both human and mouse. Our functional investigations and unbiased transcriptomic analyses clearly demonstrated that Trim16 deficiency markedly exacerbated cardiomyocyte enlargement in vitro and in transverse aortic constriction-induced cardiac hypertrophy mouse model, whereas Trim16 overexpression attenuated cardiac hypertrophy and remodeling. Mechanistically, Prdx1 (peroxiredoxin 1) is an essential target of Trim16 in cardiac hypertrophy. We found that Trim16 interacts with Prdx1 and inhibits its phosphorylation, leading to a robust enhancement of its downstream Nrf2 (nuclear factor-erythroid 2-related factor 2) pathway to block cardiac hypertrophy. Trim16-blocked Prdx1 phosphorylation was largely dependent on a direct interaction between Trim16 and Src and the resultant Src ubiquitinational degradation. Notably, Prdx1 knockdown largely abolished the anti-hypertrophic effects of Trim16 overexpression. CONCLUSIONS: Our findings provide the first evidence supporting Trim16 as a novel suppressor of pathological cardiac hypertrophy and indicate that targeting the Trim16-Prdx1 axis represents a promising therapeutic strategy for hypertrophy-related heart failure.


Asunto(s)
Cardiomegalia , Insuficiencia Cardíaca , Proteínas de Motivos Tripartitos , Ubiquitina-Proteína Ligasas , Animales , Cardiomegalia/metabolismo , Modelos Animales de Enfermedad , Insuficiencia Cardíaca/metabolismo , Ratones , Ratones Noqueados , Miocitos Cardíacos/metabolismo , Proteínas de Motivos Tripartitos/genética , Ubiquitina-Proteína Ligasas/genética
13.
Nanotechnology ; 35(36)2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38861984

RESUMEN

Electric field control of spin-orbit torque (SOT) exhibits promising potential in advanced spintronic devices through interfacial modulation. In this work, we investigate the influence of electric field and interfacial oxidation on SOT efficiency in annealed Ta/CoFeB/HfOxheterostructures. By varying annealing temperatures, the damping-like SOT efficiency reaches its peak at the annealing temperature of 320 °C, with an 80% field-free magnetization switching ratio induced by SOT having been demonstrated. This enhancement is ascribed to the annealing-induced modulation of oxygen ion migration at the CoFeB/HfOxinterface. By applying voltages across the Ta/CoFeB/HfOxheterostructures, which drives the O2‒migration across the interface, a reversible, bipolar, and non-volatile modulation of SOT efficiency was observed. The collective influence of annealing temperature and electric field effects on SOT carried out in this work provides an effective approach into facilitating the optimization and control of SOT in spintronic devices.

14.
J Biochem Mol Toxicol ; 38(1): e23602, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38053484

RESUMEN

Flavonoids, which contain a benzo-γ-pyrone (C6-C3-C6) skeleton, have been reported to exhibit effective antioxidant ability. This study aimed to compare the antioxidant activities of 7,8-dihydroxyflavone (7,8-DHF) and 7-hydroxyflavone (7-HF) in H2 O2 , lipopolysaccharide (LPS), or tert-butyl hydroperoxide (t-BHP)-induced RAW264.7 cells, respectively. The antioxidant capacities of 7,8-DHF and 7-HF were firstly evaluated by 2,2-azinobis-3-ethyl-benzothiazoline-6-sulphonic acid (ABTS), 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) assays. Then, reactive oxygen species (ROS), super oxide dismutase (SOD), and malondialdehyde (MDA) productions in H2 O2 , LPS, or t-BHP-induced RAW264.7 cells were tested and compared, respectively. Finally, the antioxidant mechanisms of 7-HF and 7,8-DHF were initially investigated by western blot. Our results showed that 7,8-DHF possessed stronger free-radical scavenging capacity than 7-HF. Both 7,8-DHF and 7-HF suppressed MDA production and ROS accumulation, improved the activity of SOD in H2 O2 , LPS, or t-BHP-induced RAW264.7 cells, respectively. And 7,8-DHF exerted a better antioxidant effect than 7-HF, especially in t-BHP-induced oxidative stress. Mechanically, 7,8-DHF prevented the activation of poly ADP-ribosepolymerase and caspase-3, meanwhile markedly upregulated the expression of HO-1 protein in t-BHP-induced oxidative stress. These results suggested that 7,8-DHF might serve as a potential pharmaceutical drug against oxidative stress injury.


Asunto(s)
Antioxidantes , Flavonas , Inhibidores de Poli(ADP-Ribosa) Polimerasas , Antioxidantes/farmacología , Antioxidantes/metabolismo , Caspasa 3/metabolismo , Lipopolisacáridos/toxicidad , Estrés Oxidativo , Inhibidores de Poli(ADP-Ribosa) Polimerasas/farmacología , Especies Reactivas de Oxígeno/metabolismo , Superóxido Dismutasa/metabolismo , Animales , Ratones
15.
Bioorg Chem ; 143: 106986, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37995641

RESUMEN

Photodynamic therapy (PDT) has emerged as a highly efficacious therapeutic modality for malignant tumors owing to its non-invasive property and minimal adverse effects. However, the pervasive hypoxic microenvironment within tumors significantly compromises the efficacy of oxygen-dependent PDT, posing a formidable challenge to the advancement of high-efficiency PDT. Here, we developed a nanostructured photosensitizer (PS) assembled by cationic and anionic zinc phthalocyanines to load oxygen-throttling drug atovaquone (ATO), which was subsequently coated with polydopamine to obtain the final product ATO/ZnPc-CA@DA. ATO/ZnPc-CA@DA exhibited excellent stability, particularly in the blood milieu. Interestingly, the acidic microenvironment can trigger drug release from ATO/ZnPc-CA@DA, leading to a significant enhancement in fluorescence and an augmented generation of reactive oxygen species (ROS). ATO/ZnPc-CA@DA can induce synergistic cytotoxicity of PS and ATO, and significantly enhance the killing ability against tumor cells under hypoxic conditions. The mechanism underlying cytotoxicity of ATO/ZnPc-CA@DA was demonstrated to be associated with augmented cell apoptosis, disruption of mitochondrial membrane potential, diminished ATP production, heightened intracellular ROS generation, and reduced intracellular oxygen consumption. The animal experiments indicated that ATO/ZnPc-CA@DA possessed enhanced tumor targeting capability, along with a reduction in PS distribution within normal organs. Furthermore, ATO/ZnPc-CA@DA exhibited enhanced inhibitory effect on tumor growth and caused aggravated damage to tumor tissue. The construction strategy of nanostructured PS and the synergistic antitumor principle of combined oxygen-throttling drugs can be applied to other PSs, thereby advancing the development of photodynamic antitumor therapy and promoting the clinical translation.


Asunto(s)
Nanopartículas , Compuestos Organometálicos , Fotoquimioterapia , Animales , Fotoquimioterapia/métodos , Especies Reactivas de Oxígeno/metabolismo , Preparaciones de Acción Retardada , Línea Celular Tumoral , Fluorescencia , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Isoindoles , Oxígeno , Compuestos Organometálicos/farmacología
16.
Acta Pharmacol Sin ; 2024 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-38671193

RESUMEN

Despite the widespread prevalence and important medical impact of insomnia, effective agents with few side effects are lacking in clinics. This is most likely due to relatively poor understanding of the etiology and pathophysiology of insomnia, and the lack of appropriate animal models for screening new compounds. As the main homeostatic, circadian, and neurochemical modulations of sleep remain essentially similar between humans and rodents, rodent models are often used to elucidate the mechanisms of insomnia and to develop novel therapeutic targets. In this article, we focus on several rodent models of insomnia induced by stress, diseases, drugs, disruption of the circadian clock, and other means such as genetic manipulation of specific neuronal activity, respectively, which could be used to screen for novel hypnotics. Moreover, important advantages and constraints of some animal models are discussed. Finally, this review highlights that the rodent models of insomnia may play a crucial role in novel drug development to optimize the management of insomnia.

17.
Acta Pharmacol Sin ; 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38982150

RESUMEN

Olfactory dysfunction is increasingly recognized as an early indicator of Alzheimer's disease (AD). Aberrations in GABAergic function and the excitatory/inhibitory (E/I) balance within the olfactory bulb (OB) have been implicated in olfactory impairment during the initial stages of AD. While the neuregulin 1 (NRG1)/ErbB4 signaling pathway is known to regulate GABAergic transmission in the brain and is associated with various neuropsychiatric disorders, its specific role in early AD-related olfactory impairment remains incompletely understood. This study demonstrated that olfactory dysfunction preceded cognitive decline in young adult APP/PS1 mice and was characterized by reduced levels of NRG1 and ErbB4 in the OB. Further investigation revealed that deletion of ErbB4 in parvalbumin interneurons reduced GABAergic transmission and increased hyperexcitability in mitral and tufted cells (M/Ts) in the OB, thereby accelerating olfactory dysfunction in young adult APP/PS1 mice. Additionally, ErbB4 deficiency was associated with increased accumulation of Aß and BACE1-mediated cleavage of APP, along with enhanced CDK5 signaling in the OB. NRG1 infusion into the OB was found to enhance GABAergic transmission in M/Ts and alleviate olfactory dysfunction in young adult APP/PS1 mice. These findings underscore the critical role of NRG1/ErbB4 signaling in regulating GABAergic transmission and E/I balance within the OB, contributing to olfactory impairment in young adult APP/PS1 mice, and provide novel insights for early intervention strategies in AD. This work has shown that ErbB4 deficiency increased the burden of Aß, impaired GABAergic transmission, and disrupted the E/I balance of mitral and tufted cells (M/Ts) in the OB, ultimately resulting in olfactory dysfunction in young adult APP/PS1 mice. NRG1 could enhance GABAergic transmission, rescue E/I imbalance in M/Ts, and alleviate olfactory dysfunction in young adult APP/PS1 mice. OB: olfactory bulb, E/I: excitation/inhibition, Pr: probability of release, PV: parvalbumin interneurons, Aß: ß-amyloid, GABA: gamma-aminobutyric acid.

18.
Langenbecks Arch Surg ; 409(1): 148, 2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38695994

RESUMEN

In the past 40 years, the incidence of esophagogastric junction cancer has been gradually increasing worldwide. Currently, surgical resection remains the main radical treatment for early gastric cancer. Due to the rise of functional preservation surgery, proximal gastrectomy has become an alternative to total gastrectomy for surgeons in Japan and South Korea. However, the methods of digestive tract reconstruction after proximal gastrectomy have not been fully unified. At present, the principal methods include esophagogastrostomy, double flap technique, jejunal interposition, and double tract reconstruction. Related studies have shown that double tract reconstruction has a good anti-reflux effect and improves postoperative nutritional prognosis, and it is expected to become a standard digestive tract reconstruction method after proximal gastrectomy. However, the optimal anastomoses mode in current double tract reconstruction is still controversial. This article aims to review the current status of double tract reconstruction and address the aforementioned issues.


Asunto(s)
Anastomosis Quirúrgica , Gastrectomía , Procedimientos de Cirugía Plástica , Neoplasias Gástricas , Humanos , Gastrectomía/métodos , Neoplasias Gástricas/cirugía , Neoplasias Gástricas/patología , Anastomosis Quirúrgica/métodos , Procedimientos de Cirugía Plástica/métodos , Unión Esofagogástrica/cirugía , Colgajos Quirúrgicos , Yeyuno/cirugía
19.
BMC Public Health ; 24(1): 1579, 2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38867197

RESUMEN

INTRODUCTION: Chlamydia trachomatis infection can cause a significant disease burden in high-risk populations. This study aimed to assess the overall prevalence of C. trachomatis infection, and determine the long-term trends and geographic distribution of this infection among female sex workers (FSWs) and men who have sex with men (MSM) in China. METHODS: The PubMed, Web of Science, CNKI, Wanfang Data and VIP databases were searched from 1 January 1990 through 30 April 2023. Publications in which C. trachomatis infection was detected using nucleic acid amplification tests (NAATs) were included. The Q test and I2 statistics were used to assess the heterogeneity between studies. A random-effect model was used to estimate the pooled prevalence of C. trachomatis infection. Subgroup, meta-regression, and sensitivity analyses were performed to explore the sources of heterogeneity. Publication bias was evaluated using Egger's test. Trend analysis of the prevalence was performed using the Jonckheere-Terpstra trend test method. RESULTS: Sixty-one studies were eligible for inclusion (including 38 for FSWs and 23 for MSM). The pooled prevalence of C. trachomatis infection was 19.5% (95% CI: 16.4, 23.0) among FSWs and 12.7% (95% CI: 9.2, 17.7) in the rectum, 6.4% (95% CI: 5.3, 7.8) in the urethra and 1.3% (95% CI: 0.8, 2.1) in the oropharynx from MSM in China. The subgroup analyses showed that the sample size, study period, study region, specimen collection type, molecular diagnosis method, and recruitment site could explain some heterogeneity among studies of FSWs, and the publication language, study period, study region, molecular diagnosis method, and specimen collection anatomical site could explain some heterogeneity among studies of MSM. From 1998 to 2004, 2005 to 2009, 2010 to 2015, and 2016 to 2021, the pooled prevalence of C. trachomatis infection among FSWs were 30.3%, 19.9%, 21.4%, and 11.3%, respectively. For MSM, the pooled prevalence from 2003 to 2009, 2010 to 2015, and 2016 to 2022 were 7.8%, 4.7%, and 6.5%, respectively. However, no overall decline in the prevalence of C. trachomatis infection was observed among FSWs (z = -1.51, P = 0.13) or MSM (z = -0.71, P = 0.48) in China. CONCLUSIONS: The prevalence of C. trachomatis infection was high in these two high-risk populations in China. The findings of this study provide evidence for the formulation of effective surveillance and screening strategies for the prevention and control of C. trachomatis infection among these two specific populations.


Asunto(s)
Infecciones por Chlamydia , Chlamydia trachomatis , Homosexualidad Masculina , Trabajadores Sexuales , Humanos , China/epidemiología , Infecciones por Chlamydia/epidemiología , Masculino , Trabajadores Sexuales/estadística & datos numéricos , Prevalencia , Homosexualidad Masculina/estadística & datos numéricos , Femenino , Chlamydia trachomatis/aislamiento & purificación
20.
Am J Otolaryngol ; 45(3): 104204, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38181649

RESUMEN

OBJECTIVE: To establish a nasopharyngeal carcinoma-specific big data platform based on electronic health records (EHRs) to provide data support for real-world study of nasopharyngeal carcinoma. METHODS: A multidisciplinary expert team was established for this project. Based on industry standards and practical feasibility, the team designed the nasopharyngeal carcinoma data element standards including 14 modules and 640 fields. Data from patients diagnosed with nasopharyngeal carcinoma who visited Southern Hospital after 1999 were extracted from 15 EHRs systems and were cleaned, structured, and standardized using information technologies such as machine learning and natural language processing. In addition, a series of measures such as quality control and data encryption were taken to ensure data quality and patient privacy. At the platform application level, 10 functional modules were designed according to the needs of nasopharyngeal carcinoma research. RESULTS: As of 1 October 2022, the Big Data platform has included 11,617patients, of whom 8228 (70.83 %) were male and 3389 (29.17 %) were female, with a median age of 48 years (interquartile range, 40 years). The data in the platform were validated to have a high level of completeness and accuracy, especially for key variables such as social demographics, laboratory tests and vital signs. Currently, six projects involving risk factors, early diagnosis, treatment efficacy and prevention of treatment-related toxic reactions have been conducted on the platform. CONCLUSIONS: We have established a high-quality NPC-specific big data platform by integrating heterogeneous data from multiple sources in the EHR. The platform provides an effective tool and strong data support for real-world studies of nasopharyngeal carcinoma, which helps to improve research efficiency, reduce costs, and improve the quality of research results. We expect to promote multicenter nasopharyngeal carcinoma data sharing in the future to facilitate the generation of high-quality real-world evidence in nasopharyngeal carcinoma. This article may provide some reference value for other comprehensive hospitals to establish a big data platform for nasopharyngeal carcinoma.


Asunto(s)
Macrodatos , Registros Electrónicos de Salud , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/terapia , Carcinoma Nasofaríngeo/diagnóstico , Masculino , Femenino , Persona de Mediana Edad , Adulto , Aprendizaje Automático , Procesamiento de Lenguaje Natural
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