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1.
Int J Surg ; 110(8): 4716-4726, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39143707

RESUMEN

BACKGROUND: In recent years, the widespread use of lipid-lowering drugs, especially statins, has attracted people's attention. Statin use may be potentially associated with a reduced risk of breast cancer. OBJECTIVE: To explore the relationship between statin use and cancer risk. And further explore the potential role of statins in the adjuvant treatment of breast cancer. METHODS: Data for the Mendelian randomization portion of the study were obtained from genome-wide association studies of common cancers in the UK Biobank and FinnGen studies and from the Global Lipid Genetics Consortium's low density lipoprotein (LDL). In addition, the impacts of statins and chemotherapy drugs on breast cancer were examined using both in vitro and in vivo models, with particular attention to the expression levels of the immune checkpoint protein PD-L1 and its potential to suppress tumor growth. RESULTS: Data from about 3.8 million cancer patients and ~1.3 million LDL-measuring individuals were analyzed. Genetically proxied HMGCR inhibition (statins) was associated with breast cancer risk reduction (P=0.0005). In vitro experiments showed that lovastatin significantly inhibited paclitaxel-induced PD-L1 expression and assisted paclitaxel in suppressing tumor cell growth. Furthermore, the combination therapy involving lovastatin and paclitaxel amplified CD8+ T-cell infiltration, bolstering their tumor-killing capacity and enhancing in vivo efficacy. CONCLUSION: The utilization of statins is correlated with improved prognoses for breast cancer patients and may play a role in facilitating the transition from cold to hot tumors. Combination therapy with lovastatin and paclitaxel enhances CD8+ T-cell activity and leads to better prognostic characteristics.


Asunto(s)
Antígeno B7-H1 , Neoplasias de la Mama , Linfocitos T CD8-positivos , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Paclitaxel , Neoplasias de la Mama/tratamiento farmacológico , Antígeno B7-H1/antagonistas & inhibidores , Antígeno B7-H1/metabolismo , Femenino , Paclitaxel/farmacología , Paclitaxel/administración & dosificación , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Pronóstico , Linfocitos T CD8-positivos/efectos de los fármacos , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , Ratones , Animales , Lovastatina/farmacología , Lovastatina/administración & dosificación , Estudio de Asociación del Genoma Completo
2.
Epilepsia ; 2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-39140981

RESUMEN

OBJECTIVE: Pharmacological activation of neuronal Kv7 channels by the antiepileptic drug retigabine (RTG; ezogabine) has been proven effective in treating partial epilepsy. However, RTG was withdrawn from the market due to the toxicity caused by its phenazinium dimer metabolites, leading to peripheral skin discoloration and retinal abnormalities. To address the undesirable metabolic properties of RTG and prevent the formation of phenazinium dimers, we made chemical modifications to RTG, resulting in a new RTG derivative, 1025c, N,N'-{4-[(4-fluorobenzyl) (prop-2-yn-1-yl)amino]-1,2-phenylene}bis(3,3-dimethylbutanamide). METHODS: Whole-cell recordings were used to evaluate Kv7 channel openers. Site-directed mutagenesis and molecular docking were adopted to investigate the molecular mechanism underlying 1025c and Kv7.2 interactions. Mouse seizure models of maximal electroshock (MES), subcutaneous pentylenetetrazol (scPTZ), and PTZ-induced kindling were utilized to test compound antiepileptic activity. RESULTS: The novel compound 1025c selectively activates whole-cell Kv7.2/7.3 currents in a concentration-dependent manner, with half-maximal effective concentration of .91 ± .17 µmol·L-1. The 1025c compound also causes a leftward shift in Kv7.2/7.3 current activation toward a more hyperpolarized membrane potential, with a shift of the half voltage of maximal activation (ΔV1/2) of -18.6 ± 3.0 mV. Intraperitoneal administration of 1025c demonstrates dose-dependent antiseizure activities in assays of MES, scPTZ, and PTZ-induced kindling models. Moreover, through site-directed mutagenesis combined with molecular docking, a key residue Trp236 has been identified as critical for 1025c-mediated activation of Kv7.2 channels. Photostability experiments further reveal that 1025c is more photostable than RTG and is unable to dimerize. SIGNIFICANCE: Our findings demonstrate that 1025c exhibits potent and selective activation of neuronal Kv7 channels without being metabolized to phenazinium dimers, suggesting its developmental potential as an antiseizure agent for therapy.

3.
Front Immunol ; 15: 1427661, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39015570

RESUMEN

Background: Osteosarcoma primarily affects children and adolescents, with current clinical treatments often resulting in poor prognosis. There has been growing evidence linking programmed cell death (PCD) to the occurrence and progression of tumors. This study aims to enhance the accuracy of OS prognosis assessment by identifying PCD-related prognostic risk genes, constructing a PCD-based OS prognostic risk model, and characterizing the function of genes within this model. Method: We retrieved osteosarcoma patient samples from TARGET and GEO databases, and manually curated literature to summarize 15 forms of programmed cell death. We collated 1621 PCD genes from literature sources as well as databases such as KEGG and GSEA. To construct our model, we integrated ten machine learning methods including Enet, Ridge, RSF, CoxBoost, plsRcox, survivalSVM, Lasso, SuperPC, StepCox, and GBM. The optimal model was chosen based on the average C-index, and named Osteosarcoma Programmed Cell Death Score (OS-PCDS). To validate the predictive performance of our model across different datasets, we employed three independent GEO validation sets. Moreover, we assessed mRNA and protein expression levels of the genes included in our model, and investigated their impact on proliferation, migration, and apoptosis of osteosarcoma cells by gene knockdown experiments. Result: In our extensive analysis, we identified 30 prognostic risk genes associated with programmed cell death (PCD) in osteosarcoma (OS). To assess the predictive power of these genes, we computed the C-index for various combinations. The model that employed the random survival forest (RSF) algorithm demonstrated superior predictive performance, significantly outperforming traditional approaches. This optimal model included five key genes: MTM1, MLH1, CLTCL1, EDIL3, and SQLE. To validate the relevance of these genes, we analyzed their mRNA and protein expression levels, revealing significant disparities between osteosarcoma cells and normal tissue cells. Specifically, the expression levels of these genes were markedly altered in OS cells, suggesting their critical role in tumor progression. Further functional validation was performed through gene knockdown experiments in U2OS cells. Knockdown of three of these genes-CLTCL1, EDIL3, and SQLE-resulted in substantial changes in proliferation rate, migration capacity, and apoptosis rate of osteosarcoma cells. These findings underscore the pivotal roles of these genes in the pathophysiology of osteosarcoma and highlight their potential as therapeutic targets. Conclusion: The five genes constituting the OS-PCDS model-CLTCL1, MTM1, MLH1, EDIL3, and SQLE-were found to significantly impact the proliferation, migration, and apoptosis of osteosarcoma cells, highlighting their potential as key prognostic markers and therapeutic targets. OS-PCDS enables accurate evaluation of the prognosis in patients with osteosarcoma.


Asunto(s)
Apoptosis , Neoplasias Óseas , Osteosarcoma , Osteosarcoma/genética , Osteosarcoma/mortalidad , Osteosarcoma/patología , Humanos , Apoptosis/genética , Pronóstico , Neoplasias Óseas/genética , Neoplasias Óseas/patología , Neoplasias Óseas/mortalidad , Regulación Neoplásica de la Expresión Génica , Biomarcadores de Tumor/genética , Línea Celular Tumoral , Aprendizaje Automático , Perfilación de la Expresión Génica , Transcriptoma , Proliferación Celular/genética , Bases de Datos Genéticas , Biología Computacional/métodos
4.
Cancer Cell Int ; 24(1): 266, 2024 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-39068476

RESUMEN

BACKGROUND: Breast cancer (BC) is a heterogeneous disease, with the ductal subtype exhibiting significant cellular diversity that influences prognosis and response to treatment. Single-cell RNA sequencing data from the GEO database were utilized in this study to investigate the underlying mechanisms of cellular heterogeneity and to identify potential prognostic markers and therapeutic targets. METHODS: Bioinformatics analysis was conducted using R packages to analyze the single-cell sequencing data. The presence of highly variable genes and differences in malignant potency within the same BC samples were examined. Differential gene expression and biological function between Type 1 and Type 2 ductal epithelial cells were identified. Lasso regression and Cox proportional hazards regression analyses were employed to identify genes associated with patient prognosis. Experimental validation was performed in vitro and in vivo to confirm the functional relevance of the identified genes. RESULTS: The analysis revealed notable heterogeneity among BC cells, with the presence of highly variable genes and differences in malignant behavior within the same samples. Significant disparities in gene expression and biological function were identified between Type 1 and Type 2 ductal epithelial cells. Through regression analyses, CYP24A1 and TFPI2 were identified as pivotal genes associated with patient prognosis. Kaplan-Meier curves demonstrated their prognostic significance, and experimental validation confirmed their inhibitory effects on malignant behaviors of ductal BC cells. CONCLUSION: This study highlights the cellular heterogeneity in ductal subtype breast cancer and delineates the differential gene expressions and biological functions between Type 1 and Type 2 ductal epithelial cells. The genes CYP24A1 and TFPI2 emerged as promising prognostic markers and therapeutic targets, exhibiting inhibitory effects on BC cell malignancy in vitro and in vivo. These findings offer the potential for improved BC management and the development of targeted treatment strategies.

5.
Chemosphere ; 362: 142863, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39019172

RESUMEN

Tetracycline (TC) is extensively utilized in livestock breeding, aquaculture, and medical industry. TC residues seriously harm food security, the environment, and human health. There is an urgent need to exploit a highly efficient and sensitive testing method to monitor TC residue levels in aquatic environments. In this study, graphitic carbon nitride quantum dots (g-CNQDs) were successfully synthesized by a one-step microwave-assisted method using citric acid and urea as precursors. The as-prepared g-CNQDs with size of 1.25-3.75 nm exhibited bright yellow fluorescence at 523 nm when excited at 397 nm. Interestingly, this characteristic fluorescence emission of g-CNQDs could be selectively and efficiently quenched by TC. Based on this phenomenon, for TC detection was successfully explored and applied in real water samples. Wide linear scope of 7-100 µM, low detection limit (LOD) of 0.48 µM, satisfactory recovery of 97.77%-103.4%, and good relative standard deviation (RSD) of 1.05-5.87% were obtained. Mechanism investigations revealed that the static quenching and the inner filter effect (IFE) were responsible for this fluorescence quenching between g-CNQDs and TC. This work not only provided a facile approach for g-CNQDs synthesis but also constructed a g-CNQDs-based fluorescent sensor platform for the highly sensitive and selective detection of TC in aquatic environments.


Asunto(s)
Grafito , Límite de Detección , Microondas , Compuestos de Nitrógeno , Puntos Cuánticos , Tetraciclina , Contaminantes Químicos del Agua , Puntos Cuánticos/química , Grafito/química , Contaminantes Químicos del Agua/análisis , Tetraciclina/análisis , Tetraciclina/química , Compuestos de Nitrógeno/química , Fluorescencia , Espectrometría de Fluorescencia , Nitrilos/química , Nitrilos/análisis , Colorantes Fluorescentes/química
6.
Chemosphere ; 362: 142790, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38971435

RESUMEN

The combination of fluorescent probe and colorimetric technique has become one of the most powerful analytical methods due to the advantages of visualization, minimal measurement errors and high sensitivity. Hence, a novel dual-modality sensing probe with both colorimetric and fluorescent capabilities was developed for detecting cobalt ions (Co2+) based on homocysteine mediated silver nanoparticles and rhodamine 6G derivatives probe (AgNPs-Hcy-Rh6G2). The fluorescence of the AgNPs-Hcy-Rh6G2 probe turned on due to the opening of the Rh6G2 spirolactam ring in the presence of Co2+ by a catalytic hydrolysis. The fluorescent intensity of probe is proportional to Co2+ concentration in the range of 0.10-50 µM with a detection limit of 0.05 µM (S/N = 3). More fascinatingly, the color of AgNPs-Hcy-Rh6G2 probe changed from colorless to pink with increasing Co2+ concentration, which allowing colorimetric determination of Co2+. The absorbance of AgNPs-Hcy-Rh6G2 probe is proportional to Co2+ concentration in the range from 0.10 to 25 µM with a detection limit of 0.04 µM (S/N = 3). This colorimetric and fluorescent dual-modal method exhibited good selectivity, and reproducibility and stability, holding great potential for real samples analysis in environmental and drug field.


Asunto(s)
Cobalto , Colorimetría , Colorantes Fluorescentes , Límite de Detección , Nanopartículas del Metal , Rodaminas , Plata , Cobalto/química , Cobalto/análisis , Plata/química , Rodaminas/química , Colorimetría/métodos , Nanopartículas del Metal/química , Colorantes Fluorescentes/química , Reproducibilidad de los Resultados , Iones/análisis , Espectrometría de Fluorescencia
7.
Prev Vet Med ; 230: 106281, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38986294

RESUMEN

Equine Infectious Anemia (EIA) is a vector-borne persistent viral infection in equine animals. The EIA is characterized by recurrent fever, thrombocytopenia, depression, anemia, rapid weight loss, and lower body edema. Control of EIA is achieved through the elimination or isolation of infected animals, resulting in significant economic losses. In recent years, many countries in Europe have experienced outbreaks of EIA, which could potentially develop into a new wave of epidemic and pose a significant threat to the healthy development of the equine industry. This study utilized spatiotemporal analysis techniques and ecological niche modeling to investigate the spatiotemporal distribution characteristics of historical EIA outbreaks and predict risk areas for EIA occurrence in Europe. Spatiotemporal analysis results indicate that from 2005 to 2023, the EIA outbreaks in Europe exhibit five significant spatiotemporal clusters, with hotspots concentrated in southeastern France and northwestern Italy. Ecological niche modeling reveals that western, central, and southern Europe are high-risk areas for EIA outbreaks. Annual mean temperature, annual precipitation, and horse density are important variables that influence the occurrence of EIA. The results of this study can provide decision-makers with valuable insights, helping with EIA monitoring and resource allocation.


Asunto(s)
Brotes de Enfermedades , Anemia Infecciosa Equina , Análisis Espacio-Temporal , Animales , Caballos , Anemia Infecciosa Equina/epidemiología , Europa (Continente)/epidemiología , Brotes de Enfermedades/veterinaria , Factores de Riesgo
8.
Mikrochim Acta ; 191(8): 477, 2024 07 22.
Artículo en Inglés | MEDLINE | ID: mdl-39039391

RESUMEN

A novel biofuel cell (BFC)-based self-powered electrochemical immunosensing platform was developed by integrating the target-induced biofuel release and biogate immunoassay for ultrasensitive 17ß-estradiol (E2) detection. The carbon nanocages/gold nanoparticle composite was employed in the BFCs device as the electrode material, through which bilirubin oxidase and glucose oxidase were wired to form the biocathode and bioanode, respectively. Positively charged mesoporous silica nanoparticles (PMSN) were encapsulated with glucose molecules as biofuel and subsequently coated by the negatively charged AuNPs-labelled anti-E2 antibody (AuNPs-Ab) serving as a biogate. The biogate could be opened efficiently and the trapped glucose released once the target E2 was recognized and captured by AuNPs-Ab due to the decreased adhesion between the antigen-antibody complex and PMSN. Then, glucose oxidase oxidized the glucose to produce a large number of electrons, resulting in significantly increased open-circuit voltage (EOCV). Promisingly, the proposed BFC-based self-powered immunosensor demonstrated exceptional sensitivity for the detection of E2 in the concentration range from 1.0 pg mL-1 to 10.0 ng mL -1, with a detection limit of 0.32 pg mL-1 (S/N = 3). Furthermore, the prepared BFC-based self-powered homogeneous immunosensor showed significant potential for implementation as a viable prototype for a mobile and an on-site bioassay system in food and environmental safety applications.


Asunto(s)
Fuentes de Energía Bioeléctrica , Técnicas Biosensibles , Estradiol , Glucosa Oxidasa , Oro , Límite de Detección , Nanopartículas del Metal , Inmunoensayo/métodos , Estradiol/química , Estradiol/análisis , Oro/química , Glucosa Oxidasa/química , Técnicas Biosensibles/métodos , Nanopartículas del Metal/química , Técnicas Electroquímicas/métodos , Técnicas Electroquímicas/instrumentación , Humanos , Electrodos , Glucosa/análisis , Oxidorreductasas actuantes sobre Donantes de Grupo CH-CH/química , Anticuerpos Inmovilizados/inmunología , Dióxido de Silicio/química , Enzimas Inmovilizadas/química
9.
FEBS Lett ; 598(15): 1888-1898, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38977940

RESUMEN

Cold stress has severe negative consequences for plant growth and crop yield. Here, we report that an Arabidopsis thaliana mutant that lacks the HPE1 gene, which encodes an RNA-binding protein, maintains higher photosynthetic activity under cold stress, together with higher accumulation of thylakoid proteins. We showed that HPE1 interacts with MORF2 and MORF9 and thereby mediates RNA editing in chloroplasts. Loss of HPE1 function increased the editing efficiency at four RNA editing sites, rpoC-488, ndhB-149, ndhB-746 and matK-706, under cold stress and altered the expression of nuclear photosynthesis-related genes and cold-responsive genes. We propose that HPE1-mediated RNA editing acts as a trigger for retrograde signaling that affects photosynthesis under cold stress.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Cloroplastos , Edición de ARN , Proteínas de Unión al ARN , Arabidopsis/genética , Arabidopsis/metabolismo , Arabidopsis/crecimiento & desarrollo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Cloroplastos/metabolismo , Cloroplastos/genética , Respuesta al Choque por Frío/genética , Regulación de la Expresión Génica de las Plantas , Mutación , Fotosíntesis , Proteínas de Unión al ARN/metabolismo , Proteínas de Unión al ARN/genética
10.
Int J Mol Sci ; 25(12)2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38928308

RESUMEN

Hepatic ischemia/reperfusion injury (IRI) is an important factor affecting liver regeneration and functional recovery postoperatively. Many studies have suggested that mesenchymal stem cells (MSCs) contribute to hepatic tissue repair and functional recovery through paracrine mechanisms mediated by exosomes. Minipigs exhibit much more similar characteristics of the liver to those of humans than rodents. This study aimed to explore whether exosomes from adipose-derived MSCs (ADSCs-exo) could actively promote liver regeneration after hepatectomy combined with HIRI in minipigs and the role they play in the cell proliferation process. This study also compared the effects and differences in the role of ADSCs and ADSCs-exo in the inflammatory response and liver regeneration. The results showed that ADSCs-exo suppressed histopathological changes and reduced inflammatory infiltration in the liver; significantly decreased levels of ALT, TBIL, HA, and the pro-inflammatory cytokines TNF-α, IL-6, and CRP; increased levels of the anti-inflammatory cytokine IL-10 and the pro-regeneration factors Ki67, PCNA, CyclinD1, HGF, STAT3, VEGF, ANG1, ANG2; and decreased levels of the anti-regeneration factors SOCS3 and TGF-ß. These indicators above showed similar changes with the ADSCs intervention group. Indicating that ADSCs-exo can exert the same role as ADSCs in regulating inflammatory responses and promoting liver regeneration. Our findings provide experimental evidence for the possibility that ADSCs-exo could be considered a safe and effective cell-free therapy to promote regeneration of injured livers.


Asunto(s)
Tejido Adiposo , Exosomas , Regeneración Hepática , Hígado , Células Madre Mesenquimatosas , Porcinos Enanos , Animales , Porcinos , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/citología , Exosomas/metabolismo , Exosomas/trasplante , Tejido Adiposo/citología , Tejido Adiposo/metabolismo , Hígado/metabolismo , Hígado/patología , Proliferación Celular , Daño por Reperfusión/terapia , Daño por Reperfusión/metabolismo , Hepatectomía , Citocinas/metabolismo , Masculino
11.
ACS Appl Mater Interfaces ; 16(27): 35293-35302, 2024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-38940838

RESUMEN

Ferroelectric materials have aroused increasing interest in the field of self-powered ultraviolet (UV) photodetectors (PDs) for their switchable spontaneous polarization. However, the utilization of ferroelectric materials to modulate the built-in electric field and energy band at the junction interface has rarely been investigated. Herein, we design and fabricate self-powered solar-blind UV PDs based on a Ga2O3/ZnO:V heterojunction. The performance of the Ga2O3/ZnO:V PD is significantly enhanced through the reasonable coupling of ferroelectricity and piezoelectricity within the ZnO:V film. The device at 260 nm exhibits excellent photoelectric properties with high peak responsivity of 64.5 mA/W, a specific detectivity of 3.8 × 1010 Jones, and a rise/decay time of 1.9/45.2 µs, together with reproducibility and stability. Systematical energy band diagram analysis reveals that the excellent performance of Ga2O3/ZnO:V PD can be attributed to the driving forces arising from the addition of the depolarization field and piezoelectric field, which increases the intensity of built-in electric field and promotes the separation and transport of photogenerated carriers at the heterojunction interface. The findings of our research provide a novel avenue and valuable guidance for the design of high-performance self-powered photodetectors.

12.
J Environ Manage ; 362: 121250, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38833921

RESUMEN

To investigate the impact and mechanism of Cd-tolerant bacteria in soil on promoting Cd accumulation in Ageratum conyzoides L., we verified the impact of inoculating two strains, B-1 (Burkholderia contaminans HA09) and B-7 (Arthrobacter humicola), on Cd accumulation in A. conyzoides through a pot experiment. Additionally, we investigated the dissolution of CdCO3 and nutrient elements, as well as the release of indoleacetic acid (IAA) by the two strains. The results showed that both strains can significantly improve the dissolution of CdCO3. Strains B-1 and B-7 had obvious effect of dissolving phosphorus, which was 5.63 and 2.76 times higher than that of the control group, respectively. Strain B-7 had significant effect of dissolution potassium, which was 1.79 times higher than that of the control group. Strains B-1 and B-7 had significant nitrogen fixation effect, which was 29.53 and 44.39 times higher than that of the control group, respectively. In addition, inoculating with strain B-1 and B-7 significantly increased the Cd extraction efficiency of A. conyzoides (by 114% and 45% respectively) through enhancing Cd accumulation and the biomass of A. conyzoides. Furthermore, the inoculation of strain B-1 and B-7 led to a significant increase in the activities of CAT and SOD, as well as the content of chlorophyll a and total chlorophyll in the leaves of A. conyzoides. To sum up, strain B-1 and B-7 can promote the phytoremediation efficiency of A. conyzoides on Cd by promoting the biomass and Cd accumulation of A. conyzoides.


Asunto(s)
Ageratum , Arthrobacter , Biodegradación Ambiental , Cadmio , Contaminantes del Suelo , Cadmio/metabolismo , Arthrobacter/metabolismo , Contaminantes del Suelo/metabolismo , Ageratum/metabolismo , Burkholderia/metabolismo , Ácidos Indolacéticos/metabolismo
13.
J Innate Immun ; 16(1): 337-353, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38815564

RESUMEN

BACKGROUND: Sepsis-associated coagulopathy specifically refers to widespread systemic coagulation activation accompanied by a high risk of hemorrhage and organ damage, which in severe cases manifests as disseminated intravascular coagulation (DIC), or even develops into multiple organ dysfunction syndrome (MODS). The complement system and the coagulation system as the main columns of innate immunity and hemostasis, respectively, undergo substantial activation after sepsis. SUMMARY: Dysfunction of the complement, coagulation/fibrinolytic cascades caused by sepsis leads to "thromboinflammation," which ultimately amplifies the systemic inflammatory response and accelerates the development of MODS. Recent studies have revealed that massive activation of the complement system exacerbates sepsis-induced coagulation and even results in DIC, which suggests that inhibition of complement activation may have therapeutic potential in the treatment of septic coagulopathy. KEY MESSAGES: Sepsis-associated thrombosis involves the upregulation or activation of procoagulant factors, down-regulation or inactivation of anticoagulant factors, and impairment of the fibrinolytic mechanism. This review aims to summarize the latest literature and analyze the underlying molecular mechanisms of the activation of the complement system on the abnormal coagulation cascades in sepsis.


Asunto(s)
Activación de Complemento , Sepsis , Humanos , Sepsis/inmunología , Activación de Complemento/inmunología , Animales , Coagulación Sanguínea , Coagulación Intravascular Diseminada/inmunología , Coagulación Intravascular Diseminada/etiología , Inmunidad Innata , Proteínas del Sistema Complemento/inmunología , Proteínas del Sistema Complemento/metabolismo , Insuficiencia Multiorgánica/inmunología , Insuficiencia Multiorgánica/etiología , Fibrinólisis , Trastornos de la Coagulación Sanguínea/inmunología , Trastornos de la Coagulación Sanguínea/etiología , Trombosis/inmunología , Trombosis/etiología
14.
Infect Dis Poverty ; 13(1): 38, 2024 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-38790027

RESUMEN

BACKGROUND: West Nile virus (WNV), the most widely distributed flavivirus causing encephalitis globally, is a vector-borne pathogen of global importance. The changing climate is poised to reshape the landscape of various infectious diseases, particularly vector-borne ones like WNV. Understanding the anticipated geographical and range shifts in disease transmission due to climate change, alongside effective adaptation strategies, is critical for mitigating future public health impacts. This scoping review aims to consolidate evidence on the impact of climate change on WNV and to identify a spectrum of applicable adaptation strategies. MAIN BODY: We systematically analyzed research articles from PubMed, Web of Science, Scopus, and EBSCOhost. Our criteria included English-language research articles published between 2007 and 2023, focusing on the impacts of climate change on WNV and related adaptation strategies. We extracted data concerning study objectives, populations, geographical focus, and specific findings. Literature was categorized into two primary themes: 1) climate-WNV associations, and 2) climate change impacts on WNV transmission, providing a clear understanding. Out of 2168 articles reviewed, 120 met our criteria. Most evidence originated from North America (59.2%) and Europe (28.3%), with a primary focus on human cases (31.7%). Studies on climate-WNV correlations (n = 83) highlighted temperature (67.5%) as a pivotal climate factor. In the analysis of climate change impacts on WNV (n = 37), most evidence suggested that climate change may affect the transmission and distribution of WNV, with the extent of the impact depending on local and regional conditions. Although few studies directly addressed the implementation of adaptation strategies for climate-induced disease transmission, the proposed strategies (n = 49) fell into six categories: 1) surveillance and monitoring (38.8%), 2) predictive modeling (18.4%), 3) cross-disciplinary collaboration (16.3%), 4) environmental management (12.2%), 5) public education (8.2%), and 6) health system readiness (6.1%). Additionally, we developed an accessible online platform to summarize the evidence on climate change impacts on WNV transmission ( https://2xzl2o-neaop.shinyapps.io/WNVScopingReview/ ). CONCLUSIONS: This review reveals that climate change may affect the transmission and distribution of WNV, but the literature reflects only a small share of the global WNV dynamics. There is an urgent need for adaptive responses to anticipate and respond to the climate-driven spread of WNV. Nevertheless, studies focusing on these adaptation responses are sparse compared to those examining the impacts of climate change. Further research on the impacts of climate change and adaptation strategies for vector-borne diseases, along with more comprehensive evidence synthesis, is needed to inform effective policy responses tailored to local contexts.


Asunto(s)
Cambio Climático , Fiebre del Nilo Occidental , Virus del Nilo Occidental , Animales , Humanos , Adaptación Fisiológica , Fiebre del Nilo Occidental/epidemiología , Fiebre del Nilo Occidental/transmisión , Fiebre del Nilo Occidental/virología , Virus del Nilo Occidental/fisiología
15.
J Immunother Cancer ; 12(5)2024 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-38821716

RESUMEN

Cytokines are small proteins that regulate the growth and functional activity of immune cells, and several have been approved for cancer therapy. Oncolytic viruses are agents that mediate antitumor activity by directly killing tumor cells and inducing immune responses. Talimogene laherparepvec is an oncolytic herpes simplex virus type 1 (oHSV), approved for the treatment of recurrent melanoma, and the virus encodes the human cytokine, granulocyte-macrophage colony-stimulating factor (GM-CSF). A significant advantage of oncolytic viruses is the ability to deliver therapeutic payloads to the tumor site that can help drive antitumor immunity. While cytokines are especially interesting as payloads, the optimal cytokine(s) used in oncolytic viruses remains controversial. In this review, we highlight preliminary data with several cytokines and chemokines, including GM-CSF, interleukin 12, FMS-like tyrosine kinase 3 ligand, tumor necrosis factor α, interleukin 2, interleukin 15, interleukin 18, chemokine (C-C motif) ligand 2, chemokine (C-C motif) ligand 5, chemokine (C-X-C motif) ligand 4, or their combinations, and show how these payloads can further enhance the antitumor immunity of oHSV. A better understanding of cytokine delivery by oHSV can help improve clinical benefit from oncolytic virus immunotherapy in patients with cancer.


Asunto(s)
Citocinas , Inmunoterapia , Neoplasias , Viroterapia Oncolítica , Virus Oncolíticos , Humanos , Viroterapia Oncolítica/métodos , Virus Oncolíticos/inmunología , Virus Oncolíticos/genética , Citocinas/metabolismo , Inmunoterapia/métodos , Neoplasias/terapia , Neoplasias/inmunología , Animales , Simplexvirus/inmunología , Simplexvirus/genética , Herpesvirus Humano 1/inmunología
16.
Bioact Mater ; 37: 299-312, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38694765

RESUMEN

Ultrahigh dose-rate (FLASH) radiotherapy is an emerging technology with excellent therapeutic effects and low biological toxicity. However, tumor recurrence largely impede the effectiveness of FLASH therapy. Overcoming tumor recurrence is crucial for practical FLASH applications. Here, we prepared an agarose-based thermosensitive hydrogel containing a mild photothermal agent (TPE-BBT) and a glutaminase inhibitor (CB-839). Within nanoparticles, TPE-BBT exhibits aggregation-induced emission peaked at 900 nm, while the unrestricted molecular motions endow TPE-BBT with a mild photothermy generation ability. The balanced photothermal effect and photoluminescence are ideal for phototheranostics. Upon 660-nm laser irradiation, the temperature-rising effect softens and hydrolyzes the hydrogel to release TPE-BBT and CB-839 into the tumor site for concurrent mild photothermal therapy and chemotherapy, jointly inhibiting homologous recombination repair of DNA. The enhanced FLASH radiotherapy efficiently kills the tumor tissue without recurrence and obvious systematic toxicity. This work deciphers the unrestricted molecular motions in bright organic fluorophores as a source of photothermy, and provides novel recurrence-resistant radiotherapy without adverse side effects.

17.
Planta ; 259(6): 131, 2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38652171

RESUMEN

MAIN CONCLUSION: The anatomical structures of Carex moorcroftii roots showing stronger plasticity during drought had a lower coefficient of variation in cell size in the same habitats, while those showing weaker plasticity had a higher coefficient of variation. The complementary relationship between these factors comprises the adaptation mechanism of the C. moorcroftii root to drought. To explore the effects of habitat drought on root anatomy of hygrophytic plants, this study focused on roots of C. moorcroftii. Five sample plots were set up along a soil moisture gradient in the Western Sichuan Plateau to collect experimental materials. Paraffin sectioning was used to obtain root anatomy, and one-way ANOVA, correlation analysis, linear regression analysis, and RDA ranking were applied to analyze the relationship between root anatomy and soil water content. The results showed that the root transverse section area, thickness of epidermal cells, exodermis and Casparian strips, and area of aerenchyma were significantly and positively correlated with soil moisture content (P < 0.01). The diameter of the vascular cylinder and the number and total area of vessels were significantly and negatively correlated with the soil moisture content (P < 0.01). The plasticity of the anatomical structures was strong for the diameter and area of the vascular cylinder and thickness of the Casparian strip and epidermis, while it was weak for vessel diameter and area. In addition, there was an asymmetrical relationship between the functional adaptation of root anatomical structure in different soil moisture and the variation degree of root anatomical structure in the same soil moisture. Therefore, the roots of C. moorcroftii can shorten the water transport distance from the epidermis to the vascular cylinder, increase the area of the vascular cylinder and the number of vessels, and establish a complementary relationship between the functional adaptation of root anatomical structure in different habitats and the variation degree of root anatomical structure in the same habitat to adapt to habitat drought. This study provides a scientific basis for understanding the response of plateau wetland plants to habitat changes and their ecological adaptation strategies. More scientific experimental methods should be adopted to further study the mutual coordination mechanisms of different anatomical structures during root adaptation to habitat drought for hygrophytic plants.


Asunto(s)
Carex (Planta) , Sequías , Ecosistema , Raíces de Plantas , Suelo , Agua , Raíces de Plantas/anatomía & histología , Raíces de Plantas/fisiología , China , Carex (Planta)/fisiología , Carex (Planta)/anatomía & histología , Agua/fisiología , Agua/metabolismo , Adaptación Fisiológica
18.
Chem Soc Rev ; 53(8): 3656-3686, 2024 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-38502089

RESUMEN

Advancements in nanochemistry have led to the development of engineered gold nanostructures (GNSs) with remarkable potential for a variety of dental healthcare applications. These innovative nanomaterials offer unique properties and functionalities that can significantly improve dental diagnostics, treatment, and overall oral healthcare applications. This review provides an overview of the latest advancements in the design, synthesis, and application of GNSs for dental healthcare applications. Engineered GNSs have emerged as versatile tools, demonstrating immense potential across different aspects of dentistry, including enhanced imaging and diagnosis, prevention, bioactive coatings, and targeted treatment of oral diseases. Key highlights encompass the precise control over GNSs' size, crystal structure, shape, and surface functionalization, enabling their integration into sensing, imaging diagnostics, drug delivery systems, and regenerative therapies. GNSs, with their exceptional biocompatibility and antimicrobial properties, have demonstrated efficacy in combating dental caries, periodontitis, peri-implantitis, and oral mucosal diseases. Additionally, they show great promise in the development of advanced sensing techniques for early diagnosis, such as nanobiosensor technology, while their role in targeted drug delivery, photothermal therapy, and immunomodulatory approaches has opened new avenues for oral cancer therapy. Challenges including long-term toxicity, biosafety, immune recognition, and personalized treatment are under rigorous investigation. As research at the intersection of nanotechnology and dentistry continues to thrive, this review highlights the transformative potential of engineered GNSs in revolutionizing dental healthcare, offering accurate, personalized, and minimally invasive solutions to address the oral health challenges of the modern era.


Asunto(s)
Oro , Oro/química , Humanos , Propiedades de Superficie , Nanopartículas del Metal/química , Odontología , Sistemas de Liberación de Medicamentos , Nanotecnología/métodos
19.
Plant Physiol ; 195(2): 1728-1744, 2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38441888

RESUMEN

Rosmarinic acid (RA) is an important medicinal metabolite and a potent food antioxidant. We discovered that exposure to high light intensifies the accumulation of RA in the leaves of perilla (Perilla frutescens (L.) Britt). However, the molecular mechanism underlying RA synthesis in response to high light stress remains poorly understood. To address this knowledge gap, we conducted a comprehensive analysis employing transcriptomic sequencing, transcriptional activation, and genetic transformation techniques. High light treatment for 1 and 48 h resulted in the upregulation of 592 and 1,060 genes, respectively. Among these genes, three structural genes and 93 transcription factors exhibited co-expression. Notably, NAC family member PfNAC2, GBF family member PfGBF3, and cinnamate-4-hydroxylase gene PfC4H demonstrated significant co-expression and upregulation under high light stress. Transcriptional activation analysis revealed that PfGBF3 binds to and activates the PfNAC2 promoter. Additionally, both PfNAC2 and PfGBF3 bind to the PfC4H promoter, thereby positively regulating PfC4H expression. Transient overexpression of PfNAC2, PfGBF3, and PfC4H, as well as stable transgenic expression of PfNAC2, led to a substantial increase in RA accumulation in perilla. Consequently, PfGBF3 acts as a photosensitive factor that positively regulates PfNAC2 and PfC4H, while PfNAC2 also regulates PfC4H to promote RA accumulation under high light stress. The elucidation of the regulatory mechanism governing RA accumulation in perilla under high light conditions provides a foundation for developing a high-yield RA system and a model to understand light-induced metabolic accumulation.


Asunto(s)
Cinamatos , Depsidos , Regulación de la Expresión Génica de las Plantas , Luz , Proteínas de Plantas , Ácido Rosmarínico , Depsidos/metabolismo , Cinamatos/metabolismo , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Perilla frutescens/genética , Perilla frutescens/metabolismo , Hojas de la Planta/metabolismo , Hojas de la Planta/genética , Hojas de la Planta/efectos de la radiación , Regiones Promotoras Genéticas/genética
20.
Analyst ; 149(9): 2621-2628, 2024 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-38546096

RESUMEN

17ß-Estradiol (E2) is an important endogenous estrogen, which disturbs the endocrine system and poses a threat to human health because of its accumulation in the human body. Herein, a biofuel cell (BFC)-based self-powered electrochemical aptasensor was developed for E2 detection. Porous carbon nanocage/gold nanoparticle composite modified indium tin oxide (CNC/AuNP/ITO) and glucose oxidase modified CNC/AuNP/ITO were used as the biocathode and bioanode of BFCs, respectively. [Fe(CN)6]3- was selected as an electroactive probe, which was entrapped in the pores of positively charged magnetic Fe3O4 nanoparticles (PMNPs) and then capped with a negatively charged E2 aptamer to form a DNA bioconjugate. The presence of the target E2 triggered the entrapped [Fe(CN)6]3- probe release due to the removal of the aptamer via specific recognition, which resulted in the transfer of electrons produced by glucose oxidation at the bioanode to the biocathode and produced a high open-circuit voltage (EOCV). Consequently, a "signal-on" homogeneous self-powered aptasensor for E2 assay was realized. Promisingly, the BFC-based self-powered aptasensor has particularly high sensitivity for E2 detection in the concentration range of 0.5 pg mL-1 to 15 ng mL-1 with a detection limit of 0.16 pg mL-1 (S/N = 3). Therefore, the proposed BFC-based self-powered electrochemical aptasensor has great promise to be applied as a successful prototype of a portable and on-site bioassay in the field of environment monitoring and food safety.


Asunto(s)
Aptámeros de Nucleótidos , Fuentes de Energía Bioeléctrica , Carbono , Técnicas Electroquímicas , Estradiol , Oro , Nanopartículas del Metal , Estradiol/química , Estradiol/análisis , Aptámeros de Nucleótidos/química , Oro/química , Nanopartículas del Metal/química , Carbono/química , Técnicas Electroquímicas/métodos , Técnicas Electroquímicas/instrumentación , Técnicas Biosensibles/métodos , Límite de Detección , Humanos , ADN/química , Glucosa Oxidasa/química , Compuestos de Estaño/química
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