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1.
Front Oncol ; 14: 1367159, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39228987

RESUMEN

Background: Neuroblastoma (NB) primarily arises in children who are <10 years of age, and originates from developing sympathetic nervous system, which results in tumors in adrenal glands and/or sympathetic ganglia. The diagnosis of NB involves a combination of laboratory and imaging tests, and biopsies. Small extracellular vesicles (sEVs) have gained attention as potential biomarkers for various types of tumors. Here, we performed proteomic analysis of serum sEVs and identified potential biomarkers for NB. Methods: Label-free proteomics of serum sEVs were performed in the discovery phase. A bulk RNA-seq dataset of NB tissues was used to analyze the association between genes encoding sEVs proteins and prognosis. Potential biomarkers were validated via multiple reaction monitoring (MRM) or western blot analysis in the validation phase. A public single-cell RNA-seq (scRNA-seq) dataset was integrated to analyze the tissue origin of sEVs harboring biomarkers. Results: A total of 104 differentially expressed proteins were identified in NB patients with label-free proteomics, and 26 potential biomarkers were validated with MRM analysis. Seven proteins BSG, HSP90AB1, SLC44A1, CHGA, ATP6V0A1, ITGAL and SELL showed the strong ability to distinguish NB patients from healthy controls and non-NB patients as well. Integrated analysis of scRNA-seq and sEVs proteomics revealed that these sEVs-derived biomarkers originated from different cell populations in tumor tissues. Conclusion: sEVs-based biomarkers may aid the molecular diagnosis of NB, representing an innovative strategy to improve NB detection and management.

2.
Inorg Chem ; 63(34): 15579-15583, 2024 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-39145687

RESUMEN

Three organic-inorganic metal iodides, namely, (NH4)(l-hp)ZnI3 (1), [Cd(l-hp)4]Cd3I8 (2), and (l-Hhp)(l-hp)PbI3 (3), have been synthesized using l-homoproline (l-hp) as the structure-directing agent. These compounds feature different noncentrosymmetric structures and optical properties. In particular, compound 3 shows a large second-harmonic-generation response of 3.4 times that of KH2PO4. Density functional theory calculations were performed to gain insight into its structure-property relationship.

3.
J Cancer Res Ther ; 20(4): 1141-1149, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39206975

RESUMEN

ABSTRACT: As the initial point for digestion, the balance of oral microorganisms plays an important role in maintaining local and systemic health. Oral dysbiosis, or an imbalance in the oral microbial community, may lead to the onset of various diseases. The presence or abnormal increase of microbes in the oral cavity has attracted significant attention due to its complicated relationship with oral cancer. Oral cancer can remodel microbial profiles by creating a more beneficial microenvironment for its progression. On the other hand, altered microbial profiles can promote tumorigenesis by evoking a complex inflammatory response and affecting host immunity. This review analyzes the oncogenic potential of oral microbiome alterations as a driver and biomarker. Additionally, a potentially therapeutic strategy via the reversal of the oral microbiome dysbiosis in oral cancers has been discussed.


Asunto(s)
Disbiosis , Microbiota , Neoplasias de la Boca , Boca , Humanos , Neoplasias de la Boca/microbiología , Neoplasias de la Boca/patología , Disbiosis/microbiología , Disbiosis/complicaciones , Disbiosis/inmunología , Boca/microbiología , Boca/patología , Microambiente Tumoral/inmunología
4.
Tissue Cell ; 90: 102520, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39137536

RESUMEN

Heat acclimation (HA) is found to help decrease the incidence of heat-related illnesses such as heat syncope and exertional heat stroke. However, the response of vascular endothelial cells to HA remain to be elucidated. In this study, mouse brain microvascular endothelial cells (bEnd.3), human umbilical vein endothelial cells (HUVEC), and human aortic endothelial cells (HAEC) were selected. The cells were first subjected to HA at 40 ℃ for 2 h per day for 3 days, and then subjected to heat stress at 43 ℃ for 2 h or 4 h. After heat stress, HA-pretreated cells showed a significant increase in cell viability, cell integrity, a decrease in the proportion of S phase cells, cell apoptosis, and cytoskeletal shrinkage compared with the cells without HA pretreatment. Additionally, the expression of VEGF, ICAM-1, iNOS and EPO in HA-pretreated cells significantly increased. We also presented evidence that HA upregulated HSP70 and bcl-2, while downregulated p-p53 and bax. Notably, the suppression of HSP70 expression attenuated the protective role of heat acclimation. Furthermore, HA mitigated injuries in vital organs of mice exposed to heat stress. Conclusively, these findings indicated the HA can increase the vitality of vascular endothelial cells after heat stress, partially restore the function of vascular endothelial cells, and this protective effect may be related to the upregulation of HSP70 expression.


Asunto(s)
Células Endoteliales , Respuesta al Choque Térmico , Células Endoteliales de la Vena Umbilical Humana , Animales , Humanos , Ratones , Células Endoteliales/metabolismo , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Apoptosis , Aclimatación , Calor , Supervivencia Celular , Proteínas HSP70 de Choque Térmico/metabolismo
5.
Neoplasia ; 56: 101025, 2024 10.
Artículo en Inglés | MEDLINE | ID: mdl-38996538

RESUMEN

The study of extrachromosomal DNA (ecDNA), an element existing beyond classical chromosomes, contributes to creating a more comprehensive map of the cancer genome. In hematological malignancies, research on ecDNA has lacked comprehensive investigation into its frequency, structure, function, and mechanisms of formation. We re-analyzed WGS data from 208 hematological cancer samples across 11 types, focusing on ecDNA characteristics. Amplification of ecDNA was observed in 7 of these cancer types, with no instances found in normal blood cells. Patients with leukemia carrying ecDNA showed a low induction therapy remission rate (<30 %), a high relapse rate (75 %) among those who achieved complete remission, and a significantly lower survival rate compared to the general leukemia population, even those with complex chromosomal karyotypes. Among the 55 identified ecDNA amplicons, 268 genes were detected, of which 38 are known cancer-related genes exhibiting significantly increased copy numbers. By integrating RNA-Seq data, we discovered that the increased copy number, resulting in a higher amount of available DNA templates, indeed leads to the elevated expression of genes encoded on ecDNA. Additionally, through the integration of H3K4me3/H3K27ac chromatin immunoprecipitation sequencing, assay for transposase-accessible chromatin with sequencing, and high-throughput chromosome conformation capture data, we identified that ecDNA amplifications can also facilitate efficient, copy number-independent amplification of oncogenes. This process is linked to active histone modifications, improved chromatin accessibility, and enhancer hijacking, all of which are effects of ecDNA amplification. Mechanistically, chromothripsis and dysfunction of the DNA repair pathway can, to some extent, explain the origin of ecDNA.


Asunto(s)
Amplificación de Genes , Neoplasias Hematológicas , Humanos , Neoplasias Hematológicas/genética , Variaciones en el Número de Copia de ADN
6.
Sci Bull (Beijing) ; 69(16): 2604-2621, 2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-39030102

RESUMEN

Preterm birth (PTB) is a leading cause of neonatal morbidity and mortality worldwide, yet the cellular and molecular mechanisms driving this condition remain undeciphered, thus limiting discovery of new therapies. In-depth analyses of human and mouse tissues associated with PTB, in combination with cellular studies, indicated that aberrantly high-expressed neutrophil cytoplasmic factor (NCF) 1 leads to oxidative distress, recruitment, and pro-inflammatory activation of neutrophils and macrophages, while sequentially overexpressed pro-inflammatory mediators induce contractions of uterine smooth muscle cells (USMCs) as well as apoptosis of USMCs and amniotic epithelial cells, thereby causing PTB. According to these new findings, we rationally engineered an amphiphilic macromolecular conjugate LPA by covalently integrating low-molecular-weight heparin, a reactive oxygen species-responsive/scavenging component, and an anti-inflammatory peptide. This bioengineered macromolecular conjugate can self-assemble into multi-bioactive nanoparticles (LPA NP). In a mouse model of PTB, LPA NP effectively delayed PTB and inhibited adverse pregnancy outcomes, by regulating NCF1-mediated oxidative-inflammatory cascades, i.e., attenuating oxidative stress, inhibiting inflammatory cell activation, reducing local inflammation, and decreasing contraction/apoptosis of myometrial cells. Packaging LPA NP into temperature-responsive, self-healing, and bioadhesive hydrogel further potentiated its in vivo efficacies after intravaginal delivery, by prolonging retention time, sustaining nanotherapy release, and increasing bioavailability in the placenta/uterus. Importantly, both the conjugate/nanotherapy and hydrogel formulations exhibited excellent safety profiles in pregnant mice, with negligible side effects on the mother and offspring.


Asunto(s)
Nanopartículas , Nacimiento Prematuro , Femenino , Embarazo , Animales , Nacimiento Prematuro/prevención & control , Humanos , Ratones , Estrés Oxidativo/efectos de los fármacos , Resultado del Embarazo , Apoptosis/efectos de los fármacos , Heparina de Bajo-Peso-Molecular/farmacología , Heparina de Bajo-Peso-Molecular/uso terapéutico , Miocitos del Músculo Liso/efectos de los fármacos , Miocitos del Músculo Liso/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Modelos Animales de Enfermedad , Neutrófilos/efectos de los fármacos , Neutrófilos/metabolismo
7.
BMC Neurosci ; 25(1): 34, 2024 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-39039434

RESUMEN

The regulation of circadian rhythms and the sleep-wake states involves in multiple neural circuits. The suprachiasmatic nucleus (SCN) is a circadian pacemaker that controls the rhythmic oscillation of mammalian behaviors. The basal forebrain (BF) is a critical brain region of sleep-wake regulation, which is the downstream of the SCN. Retrograde tracing of cholera toxin subunit B showed a direct projection from the SCN to the horizontal limbs of diagonal band (HDB), a subregion of the BF. However, the underlying function of the SCN-HDB pathway remains poorly understood. Herein, activation of this pathway significantly increased non-rapid eye movement (NREM) sleep during the dark phase by using optogenetic recordings. Moreover, activation of this pathway significantly induced NREM sleep during the dark phase for first 4 h by using chemogenetic methods. Taken together, these findings reveal that the SCN-HDB pathway participates in NREM sleep regulation and provides direct evidence of a novel SCN-related pathway involved in sleep-wake states regulation.


Asunto(s)
Vías Eferentes , Optogenética , Núcleo Supraquiasmático , Animales , Núcleo Supraquiasmático/fisiología , Masculino , Ratones , Vías Eferentes/fisiología , Ratones Endogámicos C57BL , Fases del Sueño/fisiología , Prosencéfalo Basal/fisiología , Ritmo Circadiano/fisiología , Electroencefalografía
8.
Zhongguo Zhong Yao Za Zhi ; 49(11): 3002-3011, 2024 Jun.
Artículo en Chino | MEDLINE | ID: mdl-39041160

RESUMEN

This study aims to observe the effects of the traditional Chinese medicine prescription Dahuang Zhechong Pills(DHZCP on renal aging and explore its potential multi-target effects. Rats were assigned into the normal, model, DHZCP, and vitamin E(VE)groups. Firstly, the rat model of D-galactose(D-gal)-induced renal aging was established. During the modeling period, the rats in the 4 groups were administrated with double distilled water, double distilled water, DHZCP suspension, and VE suspension, respectively,by gavage every day. On day 60 of intervention, the indicators of renal aging and injury in rats were measured, including the function,histopathological characteristics, senescence-associated ß-galactosidase( SA-ß-gal) staining, and expression levels of Klotho and proteins associated with cell cycle arrest and senescence-associated secretory phenotype(SASP) in the renal tissue. Moreover, nontargeted metabolomic analysis of the renal tissue was performed for the 4 groups of rats to screen out the potential biomarkers and metabolic pathways. Finally, the signaling pathways of key targets were preliminarily validated. The results showed that DHZCP and VE significantly improved the renal function, histopathological features of renal tubular/interstitial tissue, and degree of SA-ß-gal staining, up-regulated the expression level of Klotho, and down-regulated the expression levels of proteins associated with cell cycle arrest and SASP in the renal tissue of the aging rats. In addition, DHZCP and VE regulated the metabolites in the renal tissue of the aging rats. There were 21 common differential metabolites. Among them, 5 differential metabolites were significantly increased in the aging rats and recovered after DHZCP or VE treatment, and they were involved in the lipid metabolism and energy metabolism pathways. The areas under the curves of the groups in comparison varied within the range of 0. 88-1. DHZCP regulated multiple signaling pathways, such as the adenosine monophosphate-activated protein kinase(AMPK), cyclic guanosine monophosphate-protein kinase G( c GMP-PKG), cyclic adenylic acid( c AMP), phosphatidylinositol-3-kinase-protein kinase B( PI3K-Akt), mammalian target of rapamycin(mTOR), and autophagy signaling pathways. In addition, it affected the multiple metabolic pathways, such as renin secretion, longevity regulation pathway, diabetic cardiomyopathy, and niacin and nicotinamide metabolism. DHZCP and VE significantly up-regulated the expression level of the key proteins in the AMPK signaling pathway in the renal tissue of the aging rats. In all, DHZCP and VE could mitigate renal aging and injury. DHZCP exerted multi-target effects via multiple signaling pathways and metabolic pathways in the kidney, in which the AMPK signaling pathway may be one of the key targets for action.


Asunto(s)
Envejecimiento , Medicamentos Herbarios Chinos , Riñón , Metabolómica , Ratas Sprague-Dawley , Animales , Medicamentos Herbarios Chinos/administración & dosificación , Medicamentos Herbarios Chinos/farmacología , Ratas , Riñón/efectos de los fármacos , Riñón/metabolismo , Envejecimiento/efectos de los fármacos , Envejecimiento/metabolismo , Masculino , Transducción de Señal/efectos de los fármacos
9.
Neurochem Res ; 49(10): 2926-2939, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39078522

RESUMEN

Dexmedetomidine (DEX) is a highly selective α2-adrenoceptor agonist with sedative effects on sleep homeostasis. Oxytocin-expressing (OXT) neurons in the paraventricular nucleus (PVN) of the hypothalamus (PVNOXT) regulate sexual reproduction, drinking, sleep-wakefulness, and other instinctive behaviors. To investigate the effect of DEX on the activity and signal transmission of PVNOXT in regulating the sleep-wakefulness cycle. Here, we employed OXT-cre mice to selectively target and express the designer receptors exclusively activated by designer drugs (DREADD)-based chemogenetic tool hM3D(Gq) in PVNOXT neurons. Combining chemogenetic methods with electroencephalogram (EEG) /electromyogram (EMG) recordings, we found that cannula injection of DEX in PVN significantly increased the duration of non-rapid eye movement (NREM) sleep in mice. Furthermore, the chemogenetic activation of PVNOXT neurons using i.p. injection of clozapine N-oxide (CNO) after cannula injection of DEX to PVN led to a substantial increase in wakefulness. Electrophysiological results showed that DEX decreased the frequency of action potential (AP) and the spontaneous excitatory postsynaptic current (sEPSC) of PVNOXT neurons through α2-adrenoceptors. Therefore, these results identify that DEX promotes sleep and maintains sleep homeostasis by inhibiting PVNOXT neurons through the α2-adrenoceptor.


Asunto(s)
Dexmedetomidina , Neuronas , Oxitocina , Núcleo Hipotalámico Paraventricular , Animales , Dexmedetomidina/farmacología , Núcleo Hipotalámico Paraventricular/efectos de los fármacos , Núcleo Hipotalámico Paraventricular/metabolismo , Oxitocina/farmacología , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Ratones , Masculino , Vigilia/efectos de los fármacos , Vigilia/fisiología , Agonistas de Receptores Adrenérgicos alfa 2/farmacología , Ratones Transgénicos , Ratones Endogámicos C57BL , Hipnóticos y Sedantes/farmacología , Sueño/efectos de los fármacos , Sueño/fisiología
10.
J Antimicrob Chemother ; 79(8): 1951-1961, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-38863365

RESUMEN

OBJECTIVES: Pseudomonas aeruginosa and Acinetobacter baumannii are ranked as top-priority organisms by WHO. Antimicrobial peptides (AMPs) are promising antimicrobial agents that are highly effective against serious bacterial infections. METHODS: In our previous study, a series of α-helical AMPs were screened using a novel multiple-descriptor strategy. The current research suggested that S24 exhibited strong antimicrobial activity against major pathogenic bacteria, and displayed minimal haemolysis, good serum stability and maintained salt resistance. RESULTS: We found that S24 exerted an antimicrobial effect by destroying outer membrane permeability and producing a strong binding effect on bacterial genomic DNA that inhibits genomic DNA migration. Furthermore, S24 exerted a strong ability to promote healing in wound infected by P. aeruginosa, A. baumannii and mixed strains in a mouse model. CONCLUSIONS: Overall, S24 showed good stability under physiological conditions and excellent antimicrobial activity, suggesting it may be a potential candidate for the development of serious bacterial infection treatment.


Asunto(s)
Infecciones por Acinetobacter , Acinetobacter baumannii , Antibacterianos , Pruebas de Sensibilidad Microbiana , Infecciones por Pseudomonas , Pseudomonas aeruginosa , Infección de Heridas , Acinetobacter baumannii/efectos de los fármacos , Pseudomonas aeruginosa/efectos de los fármacos , Animales , Infección de Heridas/tratamiento farmacológico , Infección de Heridas/microbiología , Ratones , Infecciones por Acinetobacter/tratamiento farmacológico , Infecciones por Acinetobacter/microbiología , Infecciones por Pseudomonas/tratamiento farmacológico , Infecciones por Pseudomonas/microbiología , Antibacterianos/farmacología , Péptidos Antimicrobianos/farmacología , Péptidos Antimicrobianos/química , Modelos Animales de Enfermedad , Permeabilidad de la Membrana Celular/efectos de los fármacos , Humanos , ADN Bacteriano/genética
11.
Avian Pathol ; : 1-10, 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38887084

RESUMEN

Ascites syndrome (AS) in broiler chickens, also known as pulmonary arterial hypertension (PAH), is a significant disease in the poultry industry. It is a nutritional metabolic disease that is closely associated with hypoxia-inducible factors and rapid growth. The rise in pulmonary artery pressure is a crucial characteristic of AS and is instrumental in its development. Hypoxia-inducible factor 1α (HIF-1α) is an active subunit of a key transcription factor in the oxygen-sensing pathway. HIF-1α plays a vital role in oxygen homeostasis and the development of pulmonary hypertension. Studying the effects of HIF-1α on pulmonary hypertension in humans or mammals, as well as ascites in broilers, can help us understand the pathogenesis of AS. Therefore, this review aims to (1) summarize the mechanism of HIF-1α in the development of pulmonary hypertension, (2) provide theoretical significance in explaining the mechanism of HIF-1α in the development of pulmonary arterial hypertension (ascites syndrome) in broilers, and (3) establish the correlation between HIF-1α and pulmonary arterial hypertension (ascites syndrome) in broilers. HIGHLIGHTSExplains the hypoxic mechanism of HIF-1α.Linking HIF-1α to pulmonary hypertension in broilers.Explains the role of microRNAs in pulmonary arterial hypertension in broilers.

12.
BMC Nephrol ; 25(1): 195, 2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38862887

RESUMEN

BACKGROUND: Acute kidney injury (AKI) is a common and serious condition, particularly among elderly patients. It is associated with high morbidity and mortality rates, further compounded by the need for continuous renal replacement therapy in severe cases. To improve clinical decision-making and patient management, there is a need for accurate prediction models that can identify patients at a high risk of mortality. METHODS: Data were extracted from the Dryad Digital Repository. Multivariate analysis was performed using least absolute shrinkage and selection operator (LASSO) logistic regression analysis to identify independent risk factors and construct a predictive nomogram for mortality within 28 days after continuous renal replacement therapy in elderly patients with acute kidney injury. The discrimination of the model was evaluated in the validation cohort using the area under the receiver operating characteristic curve (AUC), and calibration was evaluated using a calibration curve. The clinical utility of the model was assessed using decision curve analysis (DCA). RESULTS: A total of 606 participants were enrolled and randomly divided into two groups: a training cohort (n = 424) and a validation cohort (n = 182) in a 7:3 proportion. A risk prediction model was developed to identify independent predictors of 28-day mortality in elderly patients with AKI. The predictors included age, systolic blood pressure, creatinine, albumin, phosphorus, age-adjusted Charlson Comorbidity Index (CCI), Acute Physiology and Chronic Health Evaluation II (APACHE II) score, and sequential organ failure assessment (SOFA) score. These predictors were incorporated into a logistic model and presented in a user-friendly nomogram. In the validation cohort, the model demonstrated good predictive performance with an AUC of 0.799. The calibration curve showed that the model was well calibrated. Additionally, DCA revealed significant net benefits of the nomogram for clinical application. CONCLUSION: The development of a nomogram for predicting 28-day mortality in elderly patients with AKI receiving continuous renal replacement therapy has the potential to improve prognostic accuracy and assist in clinical decision-making.


Asunto(s)
Lesión Renal Aguda , Terapia de Reemplazo Renal Continuo , Nomogramas , Humanos , Femenino , Lesión Renal Aguda/mortalidad , Lesión Renal Aguda/terapia , Masculino , Anciano , Estudios Retrospectivos , Anciano de 80 o más Años , Estudios de Cohortes , Factores de Riesgo , Medición de Riesgo/métodos
13.
Anticancer Drugs ; 35(7): 597-605, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-38728095

RESUMEN

Chemotherapy failure and resistance are the leading causes of mortality in patients with acute myeloid leukemia (AML). However, the role of m6A demethylase FTO and its inhibitor rhein in AML and AML drug resistance is unclear. Therefore, this study aimed to investigate the antileukemic effect of rhein on AML and explore its potential mechanisms underlying drug resistance. Bone marrow fluid was collected to assess FTO expression in AML. The Cell Counting Kit 8 reagent was used to assess cell viability. Migration assays were conducted to assess the cell migration capacity. Flow cytometry was used to determine the apoptotic effects of rhein and western blot analysis was used to detect protein expression. Online SynergyFinder software was used to calculate the drug synergy scores. The in-vivo antileukemic effect of rhein was assessed in an AML xenograft mouse model. We analyzed different types of AML bone marrow specimens to confirm that FTO is overexpressed in AML, particularly in cases of multidrug resistance. Subsequently, we conducted in-vivo and in-vitro investigations to explore the pharmacological activity and mechanism of rhein in AML and AML with multidrug resistance. The findings demonstrated that rhein effectively suppressed the proliferation and migration of AML cells in a time- and dose-dependent manner and induced apoptosis. Rhein targets FTO, inhibits the AKT/mTOR pathway, and exhibits synergistic antitumor effects when combined with azacitidine. This study elucidates the significant role of FTO and its inhibitor rhein in AML and AML with multidrug resistance, providing new insights for overcoming multidrug resistance in AML.


Asunto(s)
Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato , Antraquinonas , Apoptosis , Resistencia a Antineoplásicos , Leucemia Mieloide Aguda , Proteínas Proto-Oncogénicas c-akt , Serina-Treonina Quinasas TOR , Ensayos Antitumor por Modelo de Xenoinjerto , Humanos , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/patología , Leucemia Mieloide Aguda/metabolismo , Animales , Ratones , Antraquinonas/farmacología , Resistencia a Antineoplásicos/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Apoptosis/efectos de los fármacos , Resistencia a Múltiples Medicamentos/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Femenino , Masculino , Movimiento Celular/efectos de los fármacos , Línea Celular Tumoral , Ratones Desnudos , Persona de Mediana Edad , Ratones Endogámicos BALB C , Transducción de Señal/efectos de los fármacos
14.
Aging (Albany NY) ; 16(10): 8944-8964, 2024 05 22.
Artículo en Inglés | MEDLINE | ID: mdl-38787377

RESUMEN

SLAMF8, the eighth member of the Signaling Lymphocytic Activation Molecule Family (SLAMF), functions in the regulation of the development and activity of diverse immune cells as a costimulatory receptor within the SLAMF family. Studies had revealed that SLAMF8 is expressed higher in several autoimmune inflammation diseases and tumors. Nevertheless, the connection between SLAMF8 and pan-cancer remains undisclosed. The research investigated the correlation between SLAMF8 and various factors including the immune microenvironment, microsatellite instability, immune novel antigen, gene mutation, immune regulatory factors, immune blockade TMB, and immune or molecular subtypes of SLAMF8 in verse cancer types. Immunohistochemistry was ultimately employed to validate the presence of the SLAMF8 gene in various tumor types including hepatocellular carcinoma, prostate adenocarcinoma, and kidney renal clear cell carcinoma. Furthermore, the relationship between SLAMF8 expression and the therapeutic efficacy of the PD1 blockade agent, Sintilimab, treatment in gastric cancer was validated. The result of differential analysis suggested that SLAMF8 was over-expressed in pan-cancer compared with paracancerous tissues. The analysis of survival indicated a connection between SLAMF8 and the overall prognosis in different types of cancers, where higher levels of SLAMF8 were found to be significantly linked to unfavorable outcomes in patients but favorable outcome of immunotherapy in gastric cancer. Significant correlations were observed between SLAMF8 levels and pan-cancer tumorigenesis, tumor metabolism, and immunity. As a result, SLAMF8 may become an important prognostic biomarker in the majority of tumors and a hopeful gene target for immunotherapy against gastric cancer.


Asunto(s)
Inmunoterapia , Familia de Moléculas Señalizadoras de la Activación Linfocitaria , Neoplasias Gástricas , Microambiente Tumoral , Humanos , Familia de Moléculas Señalizadoras de la Activación Linfocitaria/genética , Familia de Moléculas Señalizadoras de la Activación Linfocitaria/metabolismo , Neoplasias Gástricas/inmunología , Neoplasias Gástricas/genética , Neoplasias Gástricas/terapia , Inmunoterapia/métodos , Pronóstico , Microambiente Tumoral/inmunología , Masculino , Biomarcadores de Tumor/metabolismo , Biomarcadores de Tumor/genética , Femenino , Regulación Neoplásica de la Expresión Génica
15.
Front Public Health ; 12: 1384544, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38813424

RESUMEN

Introduction: Extreme heat events caused by occupational exposure and heat waves are becoming more common. However, the molecular changes underlying the response to heat exposure in humans remain to be elucidated. Methods: This study used longitudinal multi-omics profiling to assess the impact of acute heat exposure (50°C for 30 min) in 24 subjects from a mine rescue team. Intravenous blood samples were collected before acute heat exposure (baseline) and at 5 min, 30 min, 1 h, and 24 h after acute heat exposure (recovery). In-depth multi-omics profiling was performed on each sample, including plasma proteomics (untargeted) and metabolomics (untargeted). Results: After data curation and annotation, the final dataset contained 2,473 analytes, including 478 proteins and 1995 metabolites. Time-series analysis unveiled an orchestrated molecular choreography of changes involving the immune response, coagulation, acid-base balance, oxidative stress, cytoskeleton, and energy metabolism. Further analysis through protein-protein interactions and network analysis revealed potential regulators of acute heat exposure. Moreover, novel blood-based analytes that predicted change in cardiopulmonary function after acute heat exposure were identified. Conclusion: This study provided a comprehensive investigation of the dynamic molecular changes that underlie the complex physiological processes that occur in human males who undergo heat exposure. Our findings will help health impact assessment of extreme high temperature and inspire future mechanistic and clinical studies.


Asunto(s)
Proteómica , Humanos , Masculino , Estudios Longitudinales , Adulto , Metabolómica , Calor/efectos adversos , Multiómica
16.
Dalton Trans ; 53(23): 9675-9679, 2024 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-38814118

RESUMEN

Two new histidine-templated metal phosphate-oxalates (MPOs) were prepared under solvent-free conditions. Single-crystal X-ray diffraction analysis reveals that they have layered and chainlike structures, respectively. Under ultraviolet light irradiation, the two MPOs exhibit blue luminescence originating from histidine templates. Their proton-conducting properties were also investigated under different conditions.

17.
Pain Physician ; 27(4): 253-262, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38805532

RESUMEN

BACKGROUND: In our clinical practice, we observed that some osteoporotic vertebral compression fracture patients undergoing vertebral augmentation exhibited pain in the iliac crest region. This pain aligned with the diagnostic criteria for superior cluneal neuralgia (SCN) and affected treatment satisfaction. OBJECTIVE: This study aims to clinically observe patients undergoing vertebral augmentation in a hospital setting and analyze the etiology and risk factors associated with SCN. STUDY DESIGN: Retrospective cohort study. SETTING: Inpatient population of a single center. METHODS: We retrospectively analyzed clinical data from 630 patients who underwent vertebral augmentation in our hospital from March 2022 to March 2023. Fifty-two patients enrolled in the study experienced pain that met the diagnostic criteria for superior cluneal neuralgia during the perioperative period of the vertebral augmentation procedures. Those patients were divided into 2 subgroups according to the conditions involved in the occurrence of SCN: Group A (26 patients) had either no preoperative SCN but developed it postoperatively, or had preoperative SCN that worsened or did not alleviate postoperatively. Group B (26 patients) had preoperative SCN that was relieved postoperatively. Additionally, 52 consecutive patients in March 2022 to March 2023. who did not experience SCN during the perioperative period were selected as the control group (Group C). Variables such as surgical segment, age, height, weight, body mass index, duration of hospitalization, chronic low back pain (CLBP), duration of pain, anesthesia, surgical approach, fracture pattern, preoperative visual analog scale (pre-op VAS) score, intraoperative VAS score, one-day VAS score, one-month VAS score, lumbar sacral angle, and sacral tilt angle were statistically described and analyzed. RESULTS: In our hospital, the incidence of SCN during the perioperative period of vertebral augmentation procedures is 8.25% (52/630). Among all the segments of patients who developed SCN during the perioperative period, the L1 segment had the highest proportion, which was 29.03% and 35.14% in Groups A and B, respectively. Group B and Group C showed significant differences in duration of hospitalization (P = 0.012), pre-op VAS scores (P = 0.026), and CLBP (P < 0.001). Group A had significantly higher VAS scores preoperatively (P = 0.026) and intraoperatively (P = 0.004) and in CLBP (P = 0.001) than did Group C. LIMITATIONS: This is a retrospective study. Single-center noncontrolled studies may introduce selection bias. The small sample size in each group might have also led to bias. CONCLUSION: Perioperative SCN associated with vertebral augmentation is significantly correlated with preoperative VAS scores and CLBP. In addition, intraoperative VAS scores might be a factor contributing to the nonalleviation or exacerbation of postoperative SCN.


Asunto(s)
Fracturas de la Columna Vertebral , Humanos , Estudios Retrospectivos , Masculino , Femenino , Anciano , Fracturas de la Columna Vertebral/cirugía , Persona de Mediana Edad , Neuralgia/etiología , Neuralgia/cirugía , Fracturas por Compresión/cirugía , Fracturas Osteoporóticas/cirugía , Vertebroplastia/métodos
18.
Chronobiol Int ; 41(5): 609-620, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38644696

RESUMEN

Seasonal patterns (SP) exert a notable influence on the course and prognosis of patients with affective disorders, serving as a specifier in diagnosis. However, there is limited exploration of seasonality among psychotic patients, and the distinctions in seasonality among psychiatric patients remain unclear. In this study, we enrolled 198 psychiatric patients with anxiety and depressive disorders (A&D), bipolar disorder (BD), and schizophrenia (SZ), as well as healthy college students. Online questionnaires, including the Seasonal Pattern Assessment Questionnaire (SPAQ) for seasonality, the Morningness and Eveningness Questionnaire-5 (MEQ-5) for chronotypes, and the Pittsburgh Sleep Quality Index (PSQI), were administered. The validity and reliability of the Chinese version of the SPAQ were thoroughly analyzed, revealing a Cronbach's alpha of 0.896 with a two-factor structure. Results indicated that higher seasonality was correlated with poorer sleep quality and a more delayed chronotype (p < 0.05). Significant monthly variations were particularly evident in BD, specifically in mood, appetite, weight, social activities, and sleep dimensions (p < 0.001). In summary, the Chinese version of SPAQ is validated, demonstrating moderate correlations between seasonality, chronotype, and sleep quality. BD patients exhibited the strongest seasonality, while mood disorder patients displayed more delayed chronotypes than SZ.


Asunto(s)
Ritmo Circadiano , Estaciones del Año , Humanos , Masculino , Femenino , Encuestas y Cuestionarios , Adulto , Ritmo Circadiano/fisiología , Adulto Joven , Persona de Mediana Edad , Reproducibilidad de los Resultados , Pueblo Asiatico , Trastorno Bipolar/diagnóstico , Trastorno Bipolar/fisiopatología , Sueño/fisiología , Calidad del Sueño , China/epidemiología , Esquizofrenia/fisiopatología , Esquizofrenia/diagnóstico , Trastornos Mentales/diagnóstico , Trastornos Mentales/fisiopatología , Adolescente
19.
ACS Nano ; 18(18): 11988-12009, 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38652114

RESUMEN

Periodontitis, a chronic oral disease instigated by bacteria, severely compromises human oral health. The prevailing clinical treatment for periodontitis involves mechanical scraping in conjunction with antibiotics. Phototherapy is employed to rapidly remove the bacteria and achieve periodontitis treatment, effectively circumventing the adverse effects associated with traditional therapies. Constructing 2D/2D van der Waals (VDW) heterojunctions is a key strategy for obtaining excellent photocatalytic activity. Herein, a 2D/2D violet phosphorus (VP)/Ti3C2 VDW heterojunction is designed using an interfacial engineering strategy. By constructing an electron transport "bridge" (P-Ti bond) at the heterogeneous interface as an effective transfer channel for photogenerated carriers, a compact monolithic structure between the VP and Ti3C2 phases is formed, and the spatial barrier for electron transfer at the interface is eliminated. Meanwhile, the strong directional built-in electric field induced by the intensive electron-coupling effect at the heterogeneous interface served as an internal driving force, which greatly accelerates the exciton dissociation and charge transfer in the photocatalytic process. These excited photogenerated electrons and holes are trapped by O2 and H2O on the surfaces of Ti3C2 and VP, respectively, and are subsequently catalytically converted to antibacterial reactive oxygen species (ROS). The VP/Ti3C2 VDW heterojunction eradicated 97.5% and 98.48% of Staphylococcus aureus and Escherichia coli, respectively, by photocatalytic and photothermal effects under visible light for 10 min. The VP/Ti3C2 nanoperiodontal dressing ointment effectively attenuated inflammatory response, reduced alveolar bone resorption, and promoted periodontal soft and hard tissue repair. Its periodontitis therapeutic effect outperforms the clinically used Periocline.


Asunto(s)
Periodontitis , Fósforo , Titanio , Periodontitis/microbiología , Periodontitis/terapia , Fósforo/química , Titanio/química , Fototerapia , Antibacterianos/química , Antibacterianos/farmacología , Humanos , Staphylococcus aureus/efectos de los fármacos , Escherichia coli , Electricidad , Especies Reactivas de Oxígeno/metabolismo , Especies Reactivas de Oxígeno/química , Propiedades de Superficie , Animales , Transporte de Electrón , Pruebas de Sensibilidad Microbiana
20.
Inorg Chem ; 63(18): 8013-8017, 2024 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-38652668

RESUMEN

Three new homochiral metal bromides, namely, (l-Htp)2Cu2Br4 (1), (l-Htp)(l-tp)CdBr3 (2), and (l-tp)2ZnBr2 (3), were prepared using l-thioproline as the chiral template. These compounds feature dimeric, chainlike, and monomeric structures. Their second-harmonic-generation (SHG) efficiencies are 0.1, 0.3, and 2.0 times that of KH2PO4, respectively. Density functional theory calculations were performed to reveal the origin of the SHG response of compound 3.

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