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1.
World J Clin Cases ; 12(22): 4947-4955, 2024 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-39109038

RESUMEN

BACKGROUND: Preschoolers become anxious when they are about to undergo anesthesia and surgery, warranting the development of more appropriate and effective interventions. AIM: To explore the effect of static cartoons combined with dynamic virtual environments on preoperative anxiety and anesthesia induction compliance in preschool-aged children undergoing surgery. METHODS: One hundred and sixteen preschool-aged children were selected and assigned to the drug (n = 37), intervention (n = 40), and control (n = 39) groups. All the children received routine preoperative checkups and nursing before being transferred to the preoperative preparation room on the day of the operation. The drug group received 0.5 mg/kg midazolam and the intervention group treatment consisting of static cartoons combined with dynamic virtual environments. The control group received no intervention. The modified Yale Preoperative Anxiety Scale was used to evaluate the children's anxiety level on the day before surgery (T0), before leaving the preoperative preparation room (T1), when entering the operating room (T2), and at anesthesia induction (T3). Compliance during anesthesia induction (T3) was evaluated using the Induction Compliance Checklist (ICC). Changes in mean arterial pressure (MAP), heart rate (HR), and respiratory rate (RR) were also recorded at each time point. RESULTS: The anxiety scores of the three groups increased variously at T1 and T2. At T3, both the drug and intervention groups had similar anxiety scores, both of which were lower than those in the control group. At T1 and T2, MAP, HR, and RR of the three groups increased. The drug and control groups had significantly higher MAP and RR than the intervention group at T2. At T3, the MAP, HR, and RR of the drug group decreased and were significantly lower than those in the control group but were comparable to those in the intervention group. Both the drug and intervention groups had similar ICC scores and duration of anesthesia induction (T3), both of which were higher than those of the control group. CONCLUSION: Combining static cartoons with dynamic virtual environments as effective as medication, specifically midazolam, in reducing preoperative anxiety and fear in preschool-aged children. This approach also improve their compliance during anesthesia induction and helped maintain their stable vital signs.

2.
PLoS One ; 19(8): e0308412, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39116100

RESUMEN

Implementing the rural revitalization strategy is crucial for ensuring and enhancing the livelihoods of the vast rural population. The upgrading of rural consumption reflects the gradual realization of rural residents' pursuit of a better life, and the rapid development of digital inclusive finance provides strong support for this. Based on the Digital Inclusive Finance Index released by Peking University and panel data from 30 provinces across the country, this study examines the role of digital inclusive finance in optimizing rural consumption structure through the mediation effect model and analyzes its spatial spillover effects using the spatial Durbin model. The research shows that narrowing the development gap in digital inclusive finance is crucial for upgrading the rural consumption structure, which helps to promote rural residents' transition to higher-level consumption. Through the analysis of the spatial Durbin model, this study finds spatial spillover effects in this process, meaning that financial development in a particular region promotes local development but inhibits development in neighboring areas. Among various dimensions, the impact of breadth of coverage is the most significant. This trend of financial development affects consumption structure by increasing agricultural productivity and rural residents' operational income, particularly highlighting its impact on operational income. However, there are significant differences between the eastern and central-western regions in optimizing rural consumption structure, with the eastern region benefiting more while the effects in the central-western region are limited and sometimes even negative. Therefore, regional characteristics should be fully considered in policy formulation to narrow the development gap in digital inclusive finance and achieve high-quality and sustainable development.


Asunto(s)
Desarrollo Económico , Población Rural , China , Humanos , Agricultura/economía , Agricultura/métodos , Renta
3.
Colorectal Dis ; 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39080848

RESUMEN

AIM: Colorectal cancer (CRC) patients need CRC-specific dietary guidance, but often lack access to adequate nutritional information and support. This scoping review identified study interventions, online resources, which have been produced to support nutritional care self-management for CRC patients from diagnosis, through treatment and into survivorship and guidelines to underpin these. METHODS: The review was carried out in accordance with the JBI method for Scoping Reviews. Study interventions, online resources that support the self-management of nutrition and diet in CRC patients were eligible for inclusion, along with CRC-specific guidelines. Searches up to February 2023, were carried out via MEDLINE, CINAHL, PsycInfo, Embase, and Web of Science for published literature and ProQuest Dissertations, Theses Global, TRIP Medical Database, and Google search engines for grey literature. Two reviewers independently screened titles and abstracts, and relevant full texts for inclusion. Data were analysed descriptively. RESULTS: Eight study interventions, 74 online resources and three guidelines specifically aimed at CRC patients were included in the review. Study interventions were heterogenous with respect to duration, whether it was personalized, who supported delivery and which guidelines underpinned the intervention. Three study interventions resulted in improved quality of life and one lengthened survival. A total of 36 (48.6%) online resources were produced by UK charity organizations. Most of the included information was for patients after completing treatment. Specific advice for patients with a stoma was lacking. Some of the online resources provided conflicting advice. The three guidelines explained how dietary adjustments can help address symptoms related to cancer or treatment and two provided more specific guidance on making dietary changes, with specific examples of how to tailor dietary advice to patient needs. CONCLUSION: This scoping review of study interventions, online resources, and guidelines highlighted the need for reliable, detailed, and personalized information to help CRC patients to self-manage their nutritional care.

4.
Neuroscience ; 555: 76-82, 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38964453

RESUMEN

Spinocerebellar ataxia type 3 (SCA3) is a neurodegenerative disorder caused by mutant ataxin-3 with an abnormally expanded polyQ tract and is the most common dominantly inherited ataxia worldwide. There are no suitable therapeutic options for this disease. Autophagy, a defense mechanism against the toxic effects of aggregation-prone misfolded proteins, has been shown to have beneficial effects on neurodegenerative diseases. Thus, trehalose, which is an autophagy inducer, may have beneficial effects on SCA3. In the present study, we examined the effects of trehalose on an SCA3 cell model. After trehalose treatment, aggregate formation, soluble ataxin-3 protein levels and cell viability were evaluated in HEK293T cells overexpressing ataxin-3-15Q or ataxin-3-77Q. We also explored the mechanism by which trehalose affects autophagy and stress pathways. A filter trap assay showed that trehalose decreased the number of aggregates formed by mutant ataxin-3 containing an expanded polyQ tract. Western blot and Cell Counting Kit-8 (CCK-8) results demonstrated that trehalose also reduced the ataxin-3 protein levels and was safe for ataxin-3-expressing cells, respectively. Western blot and total antioxidant capacity assays suggested that trehalose had great therapeutic potential for treating SCA3, likely through its antioxidant activity. Our data indicate that trehalose plays a neuroprotective role in SCA3 by inhibiting the aggregation and reducing the protein level of ataxin-3, which is also known to protect against oxidative stress. These findings provide a new insight into the possibility of treating SCA3 with trehalose and highlight the importance of inducing autophagy in SCA3.

5.
J Am Chem Soc ; 146(29): 19852-19862, 2024 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-38982763

RESUMEN

Scattering and localization dynamics of charge carriers in the soft lattice of lead-halide perovskites impact polaron formation and recombination, which are key mechanisms of material function in optoelectronic devices. In this study, we probe the photoinduced lattice and carrier dynamics in perovskite thin films (CsFAPbX3, X = I, Br) using time-resolved infrared spectroscopy. We examine the CN stretching mode of formamidinium (FA) cations located within the lead-halide octahedra of the perovskite structure. Our investigation reveals the formation of an infrared mode due to spatial symmetry breaking within a hundred picoseconds in 3D perovskites. Experiments at cryogenic temperatures show much-reduced carrier localization, in agreement with a localization mechanism that is driven by the dynamic disorder. We extend our analysis to 2D perovskites, where the precise nature of charge carriers is uncertain. Remarkably, the signatures of charge localization we found in bulk perovskites are not observed for 2D Ruddlesden-Popper perovskites ((HexA)2FAPb2I7). This observation implies that the previously reported stabilization of free charge carriers in these materials follows different mechanisms than polaron formation in bulk perovskites. Through the exploration of heterostructures with electron/hole excess, we provide evidence that holes drive the formation of the emerging infrared mode.

7.
Cell Mol Life Sci ; 81(1): 289, 2024 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-38970696

RESUMEN

Congenital human cytomegalovirus (HCMV) infection is a major cause of abnormalities and disorders in the central nervous system (CNS) and/or the peripheral nervous system (PNS). However, the complete pathogenesis of neural differentiation disorders caused by HCMV infection remains to be fully elucidated. Stem cells from human exfoliated deciduous teeth (SHEDs) are mesenchymal stem cells (MSCs) with a high proliferation and neurogenic differentiation capacity. Since SHEDs originate from the neural crest of the early embryonic ectoderm, SHEDs were hypothesized to serve as a promising cell line for investigating the pathogenesis of neural differentiation disorders in the PNS caused by congenital HCMV infection. In this work, SHEDs were demonstrated to be fully permissive to HCMV infection and the virus was able to complete its life cycle in SHEDs. Under neurogenic inductive conditions, HCMV infection of SHEDs caused an abnormal neural morphology. The expression of stem/neural cell markers was also disturbed by HCMV infection. The impairment of neural differentiation was mainly due to a reduction of intracellular cholesterol levels caused by HCMV infection. Sterol regulatory element binding protein-2 (SREBP2) is a critical transcription regulator that guides cholesterol synthesis. HCMV infection was shown to hinder the migration of SREBP2 into nucleus and resulted in perinuclear aggregations of SREBP2 during neural differentiation. Our findings provide new insights into the prevention and treatment of nervous system diseases caused by congenital HCMV infection.


Asunto(s)
Diferenciación Celular , Colesterol , Infecciones por Citomegalovirus , Citomegalovirus , Células Madre Mesenquimatosas , Proteína 2 de Unión a Elementos Reguladores de Esteroles , Humanos , Colesterol/metabolismo , Colesterol/biosíntesis , Infecciones por Citomegalovirus/virología , Infecciones por Citomegalovirus/metabolismo , Proteína 2 de Unión a Elementos Reguladores de Esteroles/metabolismo , Proteína 2 de Unión a Elementos Reguladores de Esteroles/genética , Citomegalovirus/fisiología , Citomegalovirus/metabolismo , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/virología , Células Madre Mesenquimatosas/citología , Células Cultivadas , Diente Primario/virología , Diente Primario/citología , Diente Primario/metabolismo , Neuronas/metabolismo , Neuronas/virología , Neurogénesis
8.
Mitochondrial DNA B Resour ; 9(7): 865-870, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39010881

RESUMEN

Amorphophallus paeoniifolius (Dennst.) Nicolson, 1885, often known as elephant foot yam, is a tropical tuber crop that originates from south-east Asia and belongs to the Araceae family. It is known for its high production potential and popularity as a medicinal plant. However, the phylogeny and genes for this species are still unavailable. In this study, the first complete chloroplast genome of A. paeoniifolius was reported and phylogenetic analysis was conducted with Araceae species. The chloroplast genome was 176,258 bp in length with 34.80% overall GC content and includes a large single-copy (LSC) region (93,951 bp), a small single-copy (SSC) region (15,013 bp), and a pair of inverted repeat (IRs) regions (33,647 bp). The chloroplast genome has 130 genes, which include 85 protein-coding genes, 37 tRNA genes, and eight rRNA genes. A maximum-likelihood (ML) phylogenetic analysis indicated that all Amorphophallus species formed a single monophyletic clade with a high bootstrap value and A. paeoniifolius was closely related to A. konjac, A. albus, A. krausei, and A. titanum. The chloroplast genome reported in this study will be useful for further taxonomic and evolutionary studies of Amorphophallus.

9.
Front Pharmacol ; 15: 1429971, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38974039

RESUMEN

Introduction: Ampiroxicam is a long-acting, non-steroidal anti-inflammatory drug that selectively inhibits human cyclooxygenase, effectively mitigating fever, pain, and inflammation. This study evaluated the drug's tolerability and pharmacokinetics to support personalized dosing strategies. Methods: The study involved healthy participants and focused on the pharmacokinetics of ampiroxicam. Plasma levels of piroxicam, a key metabolite of ampiroxicam, were measured using ultra-performance liquid chromatography. Piroxicam was chosen due to its integral role in ampiroxicam's metabolic pathway. The analytical method underwent rigorous validation to ensure precision and accuracy, addressing potential interference from endogenous plasma substances. Results: Participants received ampiroxicam in single doses (low, medium, and high) and multiple doses. Pharmacokinetic parameters, including AUC0-216, AUC0-∞, and Cmax, exhibited a dose-dependent increase. No significant differences were noted across the dosage groups, and sex-specific differences were minimal, with the exception of mean residence time (MRT) in the multiple-dose group, which appeared influenced by body weight variations. Discussion: The findings affirm the safety and efficacy of ampiroxicam across different dosing regimens, validating its clinical utility and potential for personalized medicine in the treatment of pain and inflammation.

11.
Spectrochim Acta A Mol Biomol Spectrosc ; 322: 124835, 2024 Jul 14.
Artículo en Inglés | MEDLINE | ID: mdl-39024787

RESUMEN

The excited (S1) state charge distribution characteristics and fluorescence mechanism of fluorescence probes benzyl (6-cyano-2-naphthoyl)-L-valinate (NPI) and benzyl (6-amino-2-naphthoyl)-L-valinate (NPA) have been discussed using density functional theory (DFT) and time-dependent density functional theory (TD-DFT). Further analysis by constructing a torsional potential energy curve (PEC) shows that a well-defined minimum energy conformation is observed when the C-C single bond between the valine benzyl ester and naphthalene ring in NPI rotates. For NPA, the most stable conformation is the naphthalene ring conformation with dihedral angle N2C1C2C3 of -30.60°, whose total energy is 0.17 kcal/mol lower than that of the second most stable conformer. The frontier molecular orbitals (FMOs) demonstrate that NPI exhibits a low degree of charge coupling, and the oscillator intensity is close to zero, indicating that it is not conducive to luminescence. However, in the S1 state, the oscillator strength of NPA is 1.2044, which is a bright state, resulting in the strong emitting. Additionally, fluorescence imaging is favored as a visual observation technique, and Stokes shift is an important physical parameter to measure fluorescence. According to the idea that changing the number and position of functional groups can affect the photophysical properties of fluorescent dyes, o-NPDI, p-NPDI and m-NPDI dyes were newly designed and o-NPDA, p-NPDA, m-NPDA produced after recognition of Hg2+. The spectral performance results show that the newly designed fluorescent dye (p-NPDA) can not only emit in the near infrared region after recognizing Hg2+, but also has a large Stokes shift (236 nm). This indirectly reflects that para-substitution is more conducive to Stokes shift, and has become one of the strategies for fluorescent dye design.

12.
Med Sci Monit ; 30: e943414, 2024 06 28.
Artículo en Inglés | MEDLINE | ID: mdl-38937949

RESUMEN

BACKGROUND Sepsis-associated acute kidney injury (SA-AKI) is linked to high mortality rates and an unfavorable prognosis. Early identification of patients with poor prognosis is crucial. This study aimed to investigate the relationship between the systemic immune-inflammation index (SII) and mortality in this specific patient population. MATERIAL AND METHODS This retrospective cohort study used data from the Medical Information Mart for Intensive Care IV database. Data on patient demographics, comorbidities, vital signs, laboratory parameters, treatment usage, acute kidney injury staging, and renal replacement therapy were collected within 48 h of intensive care unit admission. Restricted cubic splines, Kaplan-Meier curves, and Cox regression models were used for analysis. Stratified analyses were performed on the basis of various factors. RESULTS In total, 7856 patients were included, with a median age of 66.9 years and a male-to-female ratio of 57.7%-42.3%. A J-shaped relationship was observed between SII and mortality risk. The lowest mortality risk occurred at an SII of 760.078×109/L. Compared to the reference group (second quartile of SII), the highest and third quartiles had increased 28-day mortality risk, with adjusted hazard ratios (HRs) of 1.33 (1.16-1.52) and 1.55 (1.36-1.77), respectively. Although a trend towards higher mortality hazard was observed in the lowest SII group (Q1), it was not statistically significant, with an adjusted HR of 1.15 (1-1.32). CONCLUSIONS In patients with SA-AKI, both low and high SII were associated with increased short-term mortality risk. The lowest mortality risk was observed at an SII of 760.078×109/L within a 28-day period.


Asunto(s)
Lesión Renal Aguda , Inflamación , Unidades de Cuidados Intensivos , Sepsis , Humanos , Masculino , Femenino , Estudios Retrospectivos , Sepsis/mortalidad , Sepsis/complicaciones , Sepsis/inmunología , Lesión Renal Aguda/mortalidad , Lesión Renal Aguda/inmunología , Anciano , Persona de Mediana Edad , Pronóstico , Inflamación/complicaciones , Factores de Riesgo , Modelos de Riesgos Proporcionales , Estimación de Kaplan-Meier
13.
Neurochem Res ; 49(9): 2491-2504, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38862726

RESUMEN

Idebenone, an antioxidant used in treating oxidative damage-related diseases, has unclear neuroprotective mechanisms. Oxidative stress affects cell and mitochondrial membranes, altering Adp-ribosyl cyclase (CD38) and Silent message regulator 3 (SIRT3) protein expression and possibly impacting SIRT3's ability to deacetylate Tumor protein p53 (P53). This study explores the relationship between CD38, SIRT3, and P53 in H2O2-injured HT22 cells treated with Idebenone. Apoptosis was detected using flow cytometry and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining after determining appropriate H2O2 and Idebenone concentrations.In this study, Idebenone was found to reduce apoptosis and decrease P53 and Caspase3 expression in H2O2-injured HT22 cells by detecting apoptosis-related protein expression. Through bioinformatics methods, CD38 was identified as the target of Idebenone, and it further demonstrated that Idebenone decreased the expression of CD38 and increased the level of SIRT3. An increased NAD+/NADH ratio was detected, suggesting Idebenone induces SIRT3 expression and protects HT22 cells by decreasing apoptosis-related proteins. Knocking down SIRT3 downregulated acetylated P53 (P53Ac), indicating SIRT3's importance in P53 deacetylation.These results supported that CD38 was used as a target of Idebenone to up-regulate SIRT3 to deacetylate activated P53, thereby protecting HT22 cells from oxidative stress injury. Thus, Idebenone is a drug that may show great potential in protecting against reactive oxygen species (ROS) induced diseases such as Parkinson's disease, and Alzheimer's disease. And it might be able to compensate for some of the defects associated with CD38-related diseases.


Asunto(s)
ADP-Ribosil Ciclasa 1 , Apoptosis , Estrés Oxidativo , Sirtuina 3 , Proteína p53 Supresora de Tumor , Ubiquinona , Proteína p53 Supresora de Tumor/metabolismo , Estrés Oxidativo/efectos de los fármacos , ADP-Ribosil Ciclasa 1/metabolismo , Animales , Ubiquinona/análogos & derivados , Ubiquinona/farmacología , Ratones , Sirtuina 3/metabolismo , Apoptosis/efectos de los fármacos , Línea Celular , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Peróxido de Hidrógeno/toxicidad , Antioxidantes/farmacología , Glicoproteínas de Membrana/metabolismo , Fármacos Neuroprotectores/farmacología
14.
Bioorg Med Chem ; 108: 117787, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38838580

RESUMEN

19 derivatives of 1-benzyl-3-arylpyrazole-5-carboxamides (H1-H19) and 5 derivatives of 1-benzyl-5-arylpyrazole-3-carboxamides (J1-J5) have been designed and synthesized as potential negative allosteric modulators (NAMs) for the ß2-adrenergic receptor (ß2AR). The new pyrazole derivatives were screened on the classic G-protein dependent signaling pathway at ß2AR. The majority of 1-benzyl-3-aryl-pyrazole-5-carboxamide derivatives show more potent allosteric antagonistic activity against ß2AR than Cmpd-15, the first reported ß2AR NAM. However, the 1-benzyl-5-arylpyrazole-3-carboxamide derivatives exhibit very poor or even no allosteric antagonistic activity for ß2AR. Furthermore, the active pyrazole derivatives have relative better drug-like profiles than Cmpd-15. Taken together, we discovered a series of derivatives of 1-benzyl-3-arylpyrazole-5-carboxamides as a novel scaffold of ß2AR NAM.


Asunto(s)
Receptores Adrenérgicos beta 2 , Receptores Adrenérgicos beta 2/metabolismo , Receptores Adrenérgicos beta 2/química , Regulación Alostérica/efectos de los fármacos , Humanos , Relación Estructura-Actividad , Pirazoles/química , Pirazoles/farmacología , Pirazoles/síntesis química , Estructura Molecular , Antagonistas de Receptores Adrenérgicos beta 2/farmacología , Antagonistas de Receptores Adrenérgicos beta 2/química , Antagonistas de Receptores Adrenérgicos beta 2/síntesis química
15.
Environ Sci Pollut Res Int ; 31(30): 43023-43036, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38888825

RESUMEN

So far, the physiological and molecular mechanisms of the impact of arbuscular mycorrhizal fungus (AMF) on Cd absorption, transport and detoxification in Ipomoea aquatica (water spinach) are still unclear. In the present study, a pot experiment was performed to investigate the impact of AMF-Glomus versiforme (Gv) on the photosynthetic characteristics, Cd uptake, antioxidative system and transcriptome in water spinach in the soils supplemented with 5 mg Cd kg-1. Gv inoculation improved significantly the photosynthetic characteristics and growth of water spinach. Furthermore, Gv colonization significantly promoted the activities of catalase (CAT), peroxidase (POD) and glutathione reductase (GR), contents of glutathione (GSH) and ascorbic acid (AsA), and the total antioxidant capacity (TCA), but decreased malondialdehyde (MDA) content in water spinach. In addition, Gv inoculation significantly increased pH in rhizosphere soils and decreased the Cd concentrations and uptakes in water spinach. Importantly, 2670 differentially expressed genes (DEGs) were screened in water spinach root colonized with Gv in 5 mg Cd kg-1 soil, of which 2008 DEGs were upregulated and 662 DEGs were downregulated. Especially, the expression levels of POD, CAT, GR, dehydroascorbate reductase 2 (DHAR2), glutathione S-transferase U8 (GSTU8) and glutathione synthetase (GSHS) and cytochrome P450 (Cyt P450) genes were significantly up-regulated in water spinach inoculated with Gv. Meanwhile, the plant cadmium resistance protein 2 (PCR2), metal tolerance protein 4 (MTP4), ATP-binding cassette transporter C family member (ABCC), ABC-yeast cadmium factor 1 (ABC-YCF1) and metallothionein (MT) genes were also up-regulated in mycorrhizal water spinach. Our results firstly elucidated the mechanism by which AMF reduced the uptake and phytotoxicity of Cd in water spinach through a transcriptome analysis.


Asunto(s)
Cadmio , Ipomoea , Micorrizas , Ipomoea/metabolismo , Ipomoea/genética , Cadmio/toxicidad , Micorrizas/fisiología , Glomeromycota/fisiología , Perfilación de la Expresión Génica , Contaminantes del Suelo/toxicidad , Contaminantes del Suelo/metabolismo , Transcriptoma
16.
J Med Virol ; 96(6): e29731, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38888065

RESUMEN

Severe fever with thrombocytopenia syndrome (SFTS) is associated with a high death rate and lacks a targeted therapy plan. The ratio of blood urea nitrogen to albumin, known as BAR, is a valuable method for assessing the outlook of various infectious diseases. The objective of this research was to evaluate the effectiveness of BAR in forecasting the outcome of individuals with SFTS. Four hundred and thirty-seven patients with SFTS from two clinical centers were included in this study according to inclusion and exclusion criteria. Clinical characteristics and test parameters of SFTS patients were analyzed between survival and fatal groups. Least absolute shrinkage and selection operator (LASSO) regression and Cox regression suggested that BAR might serve as a standalone prognostic indicator for patients with SFTS in the initial phase (hazard ratio = 18.669, 95% confidence interval [CI]: 8.558-40.725, p < 0.001). And BAR had a better predictive effectiveness in clinical outcomes in patients with SFTS with an AUC of 0.832 (95% CI: 0.788-0.876, p < 0.001), a cutoff value of 0.19, a sensitivity of 0.812, and a specificity of 0.726 compared to C-reactive protein, procalcitonin, and platelet to lymphocyte ratio via receiver operating characteristic curve. KM (Kaplan Meier) curves demonstrated that high level of BAR was associated with poor survival condition in patients with SFTS. Furthermore, the high level of BAR was associated with long hospital stays and test paraments of kidney, liver, and coagulation function in survival patients. So, BAR could be used as a promising early warning biomarker of adverse outcomes in patients with SFTS.


Asunto(s)
Nitrógeno de la Urea Sanguínea , Síndrome de Trombocitopenia Febril Grave , Humanos , Femenino , Masculino , Persona de Mediana Edad , Síndrome de Trombocitopenia Febril Grave/mortalidad , Síndrome de Trombocitopenia Febril Grave/sangre , Síndrome de Trombocitopenia Febril Grave/diagnóstico , Síndrome de Trombocitopenia Febril Grave/virología , Anciano , Pronóstico , Biomarcadores/sangre , Estudios Retrospectivos , Adulto , Anciano de 80 o más Años
18.
Neoplasia ; 54: 101007, 2024 08.
Artículo en Inglés | MEDLINE | ID: mdl-38796932

RESUMEN

B7-H4 is a promising immune checkpoint molecule in tumor immunotherapy. Our previous study showed that high B7-H4 expression was strongly correlated with deficiency in tumor infiltrated lymphocytes (TILs) in glioma patients. On this basis, we investigated the impact of B7-H4 on CD8+TILs in gliomas and the associated molecular mechanism here. B7-H4-positive tumor samples (n=129) from our glioma cohort were used to assess B7-H4 expression and CD8+TIL quantification by immunohistochemistry. CD8+TILs from five glioma patients cultured with B7-H4 protein were used to evaluate anti-tumor dysfunction by flow cytometry and ELISpot. An orthotopic murine glioma model was used to investigate the role of B7-H4 in glioma CD8+TILs by immunohisto- chemistry and flow cytometry. CD8+TILs from glioma patients cultured with B7-H4 protein were used to explore the potential molecular mechanism by RNA sequencing and western blot. Our results showed that glioma CD8+TIL density was negatively correlated with B7-H4 expression both in glioma patient cohort (P < 0.05) and orthotopic glioma murine model (P < 0.01). B7-H4 also lowered the expression of CD137 and CD103 (P < 0.05 for both) in glioma CD8+TILs and reduced their secretion of the anti-tumor cytokines IFN-γ and TNF-α (P < 0.01 for both) in a dose-dependent manner. Furthermore, B7-H4 was found to induce early dysfunction of glioma CD8+TILs by downregulating the phosphorylation of AKT and eNOS (P < 0.05 for both). In conclusion, B7-H4 reduced the infiltration of glioma CD8+TILs and induced an anti-tumor dysfunction phenotype. B7-H4 may also impair the anti-tumor function of glioma CD8+TILs via the AKT-eNOS pathway. These results indicated that B7-H4 may serve as a potential target in future glioma immunotherapy.


Asunto(s)
Linfocitos T CD8-positivos , Glioma , Linfocitos Infiltrantes de Tumor , Inhibidor 1 de la Activación de Células T con Dominio V-Set , Glioma/patología , Glioma/inmunología , Glioma/metabolismo , Glioma/genética , Humanos , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , Animales , Inhibidor 1 de la Activación de Células T con Dominio V-Set/metabolismo , Inhibidor 1 de la Activación de Células T con Dominio V-Set/genética , Ratones , Linfocitos Infiltrantes de Tumor/inmunología , Linfocitos Infiltrantes de Tumor/metabolismo , Línea Celular Tumoral , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/inmunología , Neoplasias Encefálicas/metabolismo , Modelos Animales de Enfermedad , Femenino , Masculino , Transducción de Señal , Persona de Mediana Edad
20.
Discov Oncol ; 15(1): 145, 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38713320

RESUMEN

BACKGROUND: C-X-C motif chemokine ligand 1 (CXCL1) and epithelial growth factor (EGF) are highly secreted by oral squamous cell carcinoma (OSCC) cells and tumor-associated macrophages, respectively. Recent studies have shown that there is intricate "cross-talk" between OSCC cells and macrophages. However, the underlying mechanisms are still poorly elucidated. METHODS: The expression of CXCL1 was detected by immunohistochemistry in OSCC clinical samples. CXCL1 levels were evaluated by RT‒PCR and ELISA in an OSCC cell line and a normal epithelial cell line. The expression of EGF was determined by RT‒PCR and ELISA. The effect of EGF on the proliferation of OSCC cells was evaluated by CCK-8 and colony formation assays. The effect of EGF on the migration and invasion ability and epithelial-mesenchymal transition (EMT) of OSCC cells was determined by wound healing, Transwell, RT‒PCR, Western blot and immunofluorescence assays. The polarization of macrophages was evaluated by RT‒PCR and flow cytometry. Western blotting was used to study the molecular mechanism in OSCC. RESULTS: The expression of C-X-C motif chemokine ligand 1 (CXCL1) was higher in the OSCC cell line (Cal27) than in immortalized human keratinocytes (Hacat cells). CXCL1 derived from Cal27 cells upregulates the expression of epithelial growth factor (EGF) in macrophages. Paracrine stimulation mediated by EGF further facilitates the epithelial-mesenchymal transition (EMT) of Cal27 cells and initiates the upregulation of CXCL1 in a positive feedback-manner. Mechanistically, EGF signaling-induced OSCC cell invasion and migration can be ascribed to the activation of NF-κB signaling mediated by the epithelial growth factor receptor (EGFR), as determined by western blotting. CONCLUSIONS: OSCC cell-derived CXCL1 can stimulate the M2 polarization of macrophages and the secretion of EGF. Moreover, EGF significantly activates NF-κB signaling and promotes the migration and invasion of OSCC cells in a paracrine manner. A positive feedback loop between OSCC cells and macrophages was formed, contributing to the promotion of OSCC progression.

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