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2.
Biomark Res ; 12(1): 111, 2024 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-39334297

RESUMEN

DNA damage response (DDR) deficiency has been one of the emerging targets in treating breast cancer in recent years. On the one hand, DDR coordinates cell cycle and signal transduction, whose dysfunction may lead to cell apoptosis, genomic instability, and tumor development. Conversely, DDR deficiency is an intrinsic feature of tumors that underlies their response to treatments that inflict DNA damage. In this review, we systematically explore various mechanisms of DDR, the rationale and research advances in DDR-targeted drugs in breast cancer, and discuss the challenges in its clinical applications. Notably, poly (ADP-ribose) polymerase (PARP) inhibitors have demonstrated favorable efficacy and safety in breast cancer with high homogenous recombination deficiency (HRD) status in a series of clinical trials. Moreover, several studies on novel DDR-related molecules are actively exploring to target tumors that become resistant to PARP inhibition. Before further clinical application of new regimens or drugs, novel and standardized biomarkers are needed to develop for accurately characterizing the benefit population and predicting efficacy. Despite the promising efficacy of DDR-related treatments, challenges of off-target toxicity and drug resistance need to be addressed. Strategies to overcome drug resistance await further exploration on DDR mechanisms, and combined targeted drugs or immunotherapy will hopefully provide more precise or combined strategies and expand potential responsive populations.

3.
Discov Oncol ; 15(1): 443, 2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39271584

RESUMEN

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is characterized by a highly metastatic potential and a heterogeneous tumor microenvironment. It exhibits limited sensitivity to conventional therapies, necessitating a deeper understanding of its pathogenesis. The role of the intratumoral microbiome in regulating cancer development in PDAC has been the subject of debate. Previous investigations into intra-tumor microbiomes have yielded uncertain results due to sample size limitations and insufficient decontamination procedures. Further research is imperative to elucidate the intricate relationship between intra-tumor microbiomes, the immune landscape of PDAC, and overall prognosis. RESULTS: Our findings revealed that the intratumor microbiota in PDAC tissue exhibited lower diversity and distinct communities compared to non-tumor tissues. The top microorganisms distinguishing between patients with long or short survival were used to construct the risk signature. We found that Stenotrophomonas is implicated in short survival of PDAC patients, while Neorickettia and Mediterraneibacter are correlated with long survival. This microbiome-based PDAC subtyping, grounded in prognosis-related signatures, exhibited significant correlations with distinct clinical prognoses and immune microenvironments. Microorganisms associated with negative prognoses were linked to pro-tumor immune activation, while those associated with positive prognoses were linked to anti-tumor immune response activation and a more favorable prognosis. CONCLUSIONS: Our PDAC subtyping approach, based on a microbiome-derived prognostic risk signature, unveiled compelling associations between the PDAC microbiota and disparities in both clinical prognosis and the tumor microenvironment. These findings suggest that microbiota may serve as a promising biomarker for predicting the prognosis of PDAC.

4.
PLoS Genet ; 20(9): e1011416, 2024 Sep 26.
Artículo en Inglés | MEDLINE | ID: mdl-39325823

RESUMEN

A previous study using Thermostable Group II Intron Reverse Transcriptase sequencing (TGIRT-seq) found human plasma contains short (≤300 nt) structured full-length excised linear intron (FLEXI) RNAs with potential to serve as blood-based biomarkers. Here, TGIRT-seq identified >9,000 different FLEXI RNAs in human cell lines, including relatively abundant FLEXIs with cell-type-specific expression patterns. Analysis of public CLIP-seq datasets identified 126 RNA-binding proteins (RBPs) that have binding sites within the region corresponding to the FLEXI or overlapping FLEXI splice sites in pre-mRNAs, including 53 RBPs with binding sites for ≥30 different FLEXIs. These included splicing factors, transcription factors, a chromatin remodeling protein, cellular growth regulators, and proteins with cytoplasmic functions. Analysis of ENCODE datasets identified subsets of these RBPs whose knockdown impacted FLEXI host gene mRNA levels or proximate alternative splicing, indicating functional interactions. Hierarchical clustering identified six subsets of RBPs whose FLEXI binding sites were co-enriched in six subsets of functionally related host genes: AGO1-4 and DICER, including but not limited to agotrons or mirtron pre-miRNAs; DKC1, NOLC1, SMNDC1, and AATF (Apoptosis Antagonizing Transcription Factor), including but not limited to snoRNA-encoding FLEXIs; two subsets of alternative splicing factors; and two subsets that included RBPs with cytoplasmic functions (e.g., LARP4, PABPC4, METAP2, and ZNF622) together with regulatory proteins. Cell fractionation experiments showed cytoplasmic enrichment of FLEXI RNAs with binding sites for RBPs with cytoplasmic functions. The subsets of host genes encoding FLEXIs with binding sites for different subsets of RBPs were co-enriched with non-FLEXI other short and long introns with binding sites for the same RBPs, suggesting overarching mechanisms for coordinately regulating expression of functionally related genes. Our findings identify FLEXIs as a previously unrecognized large class of cellular RNAs and provide a comprehensive roadmap for further analyzing their biological functions and the relationship of their RBPs to cellular regulatory mechanisms.

5.
Sci Total Environ ; 951: 175609, 2024 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-39163935

RESUMEN

As a substitute for perfluorooctane sulfonates, F-53B has permeated into the environment and can reach the human body through the food chain. Adolescent individuals are in a critical stage of development and may be more sensitive to the impacts of F-53B. In the present study, we modeled the exposure of adolescent female rats by allowing them free access to F-53B at concentrations of 0 mg/L, 0.125 mg/L, and 6.25 mg/L in drinking water, aiming to simulate the exposure in the adolescent population. Using the ovary as the focal point, we investigated the impact of developmental exposure to F-53B on female reproduction. The results indicated that F-53B induced reproductive toxicity in adolescent female rats, including ovarian lesions, follicular dysplasia and hormonal disorders. In-depth investigations revealed that F-53B induced ovarian oxidative stress, triggering autophagy within the ovaries, and the autophagy exhibited the interplay with apoptosis in turn, collectively leading to significant ovarian toxicity. Our findings provided deeper insights into the roles of the autophagy-apoptosis interplay in ovarian toxicity, and offered a new perspective on the developmental toxicity inflicted by adolescent F-53B exposure.


Asunto(s)
Apoptosis , Autofagia , Ovario , Animales , Femenino , Ratas , Autofagia/efectos de los fármacos , Ovario/efectos de los fármacos , Apoptosis/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Fluorocarburos/toxicidad , Contaminantes Químicos del Agua/toxicidad
6.
Ecotoxicol Environ Saf ; 283: 116950, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-39213750

RESUMEN

Female reproductive timing and lifespan, with a close relation to long-term health outcomes, have been altered in U.S. women over the past decades. However, epidemiologic evidence of the potential causes was lacking. On the basis of 1981 naturally postmenopausal women from the National Health and Nutrition Examination Survey 1999-2020, this study aimed to investigate the associations of urinary heavy metals with age at menarche, age at menopause, and reproductive lifespan. Multivariate generalized linear regression and addictive models were used for single metal exposure analysis, and weighted quantile sum (WQS) and Bayesian kernel machine regression (BKMR) models were employed for mixed exposures. In the fully adjusted model, higher urinary antimony concentration was associated with earlier age at menarche of 0.137 years, while higher concentrations of cadmium, cesium, lead, antimony, and thallium were associated with delayed age at menopause of 0.396-0.687 years. Additionally, urinary barium, cesium, lead, antimony, and thallium levels were associated with longer reproductive lifespan ranging between 0.277 and 0.713 years. Both WQS and BKMR models showed significantly positive associations of metal mixtures with age at menopause (ß: 0.667, 95 % CI: 0.120-1.213) and reproductive lifespan (ß: 0.686, 95 % CI: 0.092-1.280), with cadmium and lead identified as principal contributors. In conclusion, heavy metal exposures were associated with reproductive timing and lifespan of U.S. women, highlighting the need for further prevention and intervention strategies.


Asunto(s)
Menarquia , Menopausia , Metales Pesados , Reproducción , Humanos , Femenino , Metales Pesados/orina , Estudios Transversales , Menopausia/orina , Persona de Mediana Edad , Estados Unidos , Adulto , Reproducción/efectos de los fármacos , Exposición a Riesgos Ambientales/estadística & datos numéricos , Contaminantes Ambientales/orina , Encuestas Nutricionales , Anciano , Factores de Edad , Teorema de Bayes , Longevidad/efectos de los fármacos
7.
BMC Public Health ; 24(1): 1314, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38750484

RESUMEN

BACKGROUND: Medical students are known to be at a greater risk of psychological disorders compared to the general population. However, their rate of help-seeking behavior is low. The purpose of this study was to explore the influencing factors of attitudes towards psychological help-seeking among Chinese medical students and to examine its gender differences. METHODS: A total of 3,453 medical students from three medical colleges in Hainan Province, China, completed anonymous questionnaires that included socio-demographic attributes, the Family APGAR Index, the General Health Questionnaire (GHQ-20), and the Attitudes Towards Seeking Professional Psychological Help Short Form (ATSPPH-SF). Associations between predictor variables and attitudes towards help-seeking were explored using multivariate linear regression, and regression models with interaction terms were employed to test gender difference. RESULTS: The mean score on ATSPPH-SF Scale was 15.04 ± 3.45, with males scoring significantly lower than females (14.34 vs. 15.64, P < 0.0001). For both male and female groups, psych knowledge, mental health status, family function and help-seeking utility perception significantly influenced attitudes toward psychological help-seeking. Furthermore, having more than once psycho-help experiences was positively correlated with women's attitudes. Significant interactions were found between gender and mental health status. CONCLUSION: Attitude towards seeking psychological help was relatively negative among Chinese medical students. The implementation of interventions should take into account the at-risk population, especially the males and individuals with poor mental health.


Asunto(s)
Actitud del Personal de Salud , Pueblos del Este de Asia , Conducta de Búsqueda de Ayuda , Estudiantes de Medicina , Adulto , Femenino , Humanos , Masculino , Adulto Joven , China , Conocimientos, Actitudes y Práctica en Salud , Trastornos Mentales/psicología , Aceptación de la Atención de Salud/psicología , Aceptación de la Atención de Salud/estadística & datos numéricos , Factores Sexuales , Estudiantes de Medicina/psicología , Estudiantes de Medicina/estadística & datos numéricos , Encuestas y Cuestionarios
8.
Nat Commun ; 15(1): 3700, 2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38697989

RESUMEN

Detecting early-stage esophageal squamous cell carcinoma (ESCC) and precancerous lesions is critical for improving survival. Here, we conduct whole-genome bisulfite sequencing (WGBS) on 460 cfDNA samples from patients with non-metastatic ESCC or precancerous lesions and matched healthy controls. We develop an expanded multimodal analysis (EMMA) framework to simultaneously identify cfDNA methylation, copy number variants (CNVs), and fragmentation markers in cfDNA WGBS data. cfDNA methylation markers are the earliest and most sensitive, detectable in 70% of ESCCs and 50% of precancerous lesions, and associated with molecular subtypes and tumor microenvironments. CNVs and fragmentation features show high specificity but are linked to late-stage disease. EMMA significantly improves detection rates, increasing AUCs from 0.90 to 0.99, and detects 87% of ESCCs and 62% of precancerous lesions with >95% specificity in validation cohorts. Our findings demonstrate the potential of multimodal analysis of cfDNA methylome for early detection and monitoring of molecular characteristics in ESCC.


Asunto(s)
Biomarcadores de Tumor , Variaciones en el Número de Copia de ADN , Metilación de ADN , Detección Precoz del Cáncer , Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Lesiones Precancerosas , Humanos , Carcinoma de Células Escamosas de Esófago/genética , Carcinoma de Células Escamosas de Esófago/diagnóstico , Lesiones Precancerosas/genética , Lesiones Precancerosas/diagnóstico , Lesiones Precancerosas/patología , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/patología , Masculino , Detección Precoz del Cáncer/métodos , Femenino , Biomarcadores de Tumor/genética , Persona de Mediana Edad , Anciano , Epigenoma , Ácidos Nucleicos Libres de Células/genética , Ácidos Nucleicos Libres de Células/sangre , Secuenciación Completa del Genoma/métodos , Microambiente Tumoral/genética
9.
bioRxiv ; 2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38712170

RESUMEN

ATP-grasp superfamily enzymes contain a hand-like ATP-binding fold and catalyze a variety of reactions using a similar catalytic mechanism. More than 30 protein families are categorized in this superfamily, and they are involved in a plethora of cellular processes and human diseases. Here we identify C12orf29 as an atypical ATP-grasp enzyme that ligates RNA. Human C12orf29 and its homologs auto-adenylate on an active site Lys residue as part of a reaction intermediate that specifically ligates RNA halves containing a 5'-phosphate and a 3'-hydroxyl. C12orf29 binds tRNA in cells and can ligate tRNA within the anticodon loop in vitro. Genetic depletion of c12orf29 in female mice alters global tRNA levels in brain. Furthermore, crystal structures of a C12orf29 homolog from Yasminevirus bound to nucleotides reveal a minimal and atypical RNA ligase fold with a unique active site architecture that participates in catalysis. Collectively, our results identify C12orf29 as an RNA ligase and suggest its involvement in tRNA biology.

10.
Int J Biol Macromol ; 269(Pt 2): 132115, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38719015

RESUMEN

Bacterial infections pose a serious threat to human health and socioeconomics worldwide. In the post-antibiotic era, the development of novel antimicrobial agents remains a challenge. Polyphenols are natural compounds with a variety of biological activities such as intrinsic antimicrobial activity and antioxidant properties. Metal-polyphenol obtained by chelation of polyphenol ligands with metal ions not only possesses efficient antimicrobial activity but also excellent biocompatibility, which has great potential for application in biomedical and food packaging fields. Herein, we developed metal-polyphenol coordination nanosheets named copper oxidized tannic acid quinone (CuTAQ) possessing efficient antibacterial and anti-biofilm effects, which was synthesized by a facile one-pot method. The synthesis was achieved by chelation of partially oxidized tannic acid (TA) with Cu2+ under mild conditions, which supports low-cost and large-scale production. It was demonstrated that CuTAQ exhibited high antibacterial activity via disrupting the integrity of bacterial cell membranes, inducing oxidative stress, and interfering with metabolism. In addition, CuTAQ exhibits excellent peroxidase catalytic activity and photothermal conversion properties, which play a significant role in enhancing its bactericidal and biofilm scavenging abilities. This study provides insights for rational design of innovative metal-polyphenol nanomaterials with efficient antimicrobial properties.


Asunto(s)
Antibacterianos , Nanoestructuras , Polifenoles , Antibacterianos/farmacología , Antibacterianos/química , Polifenoles/química , Polifenoles/farmacología , Nanoestructuras/química , Taninos/química , Taninos/farmacología , Biopelículas/efectos de los fármacos , Cobre/química , Cobre/farmacología , Peroxidasa/metabolismo , Pruebas de Sensibilidad Microbiana , Humanos
11.
Ecotoxicol Environ Saf ; 279: 116492, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38795415

RESUMEN

Pregnant women are a special group that is sensitive to adverse external stimuli, causing metabolic abnormalities and adverse pregnancy outcomes. Microplastics (MPs), an environmental pollutant widely used in various fields, can induce a variety of toxic responses in mammals. Recent studies verified an association between MPs and metabolic disorders. Our research built a gestational mouse model in which polystyrene microplastics (PS-MPs) of 1 µm size were consumed at concentrations of 0.1, 1, and 10 mg/L during pregnancy. Results indicated that PS-MPs induced placental malfunction and fetal growth retardation. Significant glucose disorders, decreased liver function, hepatic inflammation, and oxidative stress were also observed after PS-MPs exposure. The hepatic SIRT1/IRS1/PI3K pathway was inhibited in the 10 mg/L PS-MPs exposure group. Our study found that PS-MPs activated inflammatory response and oxidative stress by increasing hepatic lipopolysaccharide (LPS) that inhibited the hepatic SIRT1/IRS1/PI3K pathway, ultimately leading to insulin resistance, glucose metabolism disorders, and adverse pregnancy outcomes. This study provides a basis for preventing environment-related gestational diabetes and concomitant adverse pregnancy outcomes.


Asunto(s)
Microplásticos , Estrés Oxidativo , Poliestirenos , Resultado del Embarazo , Sirtuina 1 , Femenino , Embarazo , Poliestirenos/toxicidad , Animales , Microplásticos/toxicidad , Ratones , Sirtuina 1/metabolismo , Estrés Oxidativo/efectos de los fármacos , Homeostasis/efectos de los fármacos , Glucosa/metabolismo , Placenta/efectos de los fármacos , Contaminantes Ambientales/toxicidad , Proteínas Sustrato del Receptor de Insulina/metabolismo , Retardo del Crecimiento Fetal/inducido químicamente , Fosfatidilinositol 3-Quinasas/metabolismo , Hígado/efectos de los fármacos
12.
Talanta ; 276: 126273, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-38776775

RESUMEN

Ultrasensitive and rapid detection of low concentration of Escherichia coli O157: H7 (E. coli O157:H7) in food is essential for food safety and public health. In this study, A novel fluorescence signal amplification biosensor based on magnetic separation platform and red fluorescent carbon dots (R-CDs)-encapsulated breakable organosilica nanocapsules (BONs) for ultrasensitive detection of E. coli O157:H7 was established. Wulff-type boronic acid functionalized magnetic nanoparticles (MNPs@B-N/APBA) with broad-spectrum bacterial recognition ability were synthesized for the first time to recognize and capture E. coli O157: H7 in food samples. R-CDs@BONs labeled with anti-E. coli O157:H7 monoclonal antibody (mAb@R-CDs@BONs-NH2) were used as the second recognition element to ensure the specificity for E. coli O157:H7 and form MNPs@B-N/APBA∼ E. coli O157:H7∼mAb@R-CDs@BONs-NH2 sandwich complexes, followed by releasing R-CDs to generate amplified fluorescence response signals for quantitative detection of E. coli O157:H7. The proposed method had a limit of detection with 25 CFU/mL in pure culture and contaminated lettuce samples, which the whole detection process took about 120 min. This fluorescence signal amplification biosensor has the potential to detect other pathogens in food by altering specific antibodies.


Asunto(s)
Técnicas Biosensibles , Carbono , Escherichia coli O157 , Puntos Cuánticos , Escherichia coli O157/aislamiento & purificación , Técnicas Biosensibles/métodos , Carbono/química , Puntos Cuánticos/química , Nanocápsulas/química , Colorantes Fluorescentes/química , Fluorescencia , Límite de Detección , Compuestos de Organosilicio/química , Microbiología de Alimentos , Lactuca/microbiología , Lactuca/química
13.
Ecotoxicol Environ Saf ; 279: 116501, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38805831

RESUMEN

6:2 Chlorinated polyfluoroalkyl ether sulfonate (F-53B) is a new type of perfluorinated and polyfluoroalkyl substance (PFAS) that is used extensively in industry and manufacturing. F-53B causes damage to multiple mammalian organs. However, the impacts of F-53B on bone are unknown. Maternal exposure to F-53B is of particular concern because of the vulnerability of the developing fetus and newborn to contaminants from the mother. The goal of this study was to examine the impacts of maternal F-53B exposure on bone growth and development in offspring and to explore its underlying mechanisms. Herein, C57BL/6 J mice were given free access to deionized water containing 0, 0.57, or 5.7 mg/L F-53B during pregnancy and lactation. F-53B exposure resulted in impaired liver function, decreased IGF-1 secretion, dysregulation of bone metabolism and disruption of the dynamic balance between osteoblasts and osteoclasts in male offspring. F-53B inhibits longitudinal bone growth and development and causes osteoporosis in male offspring. F-53B may affect the growth and development of offspring bone via the IGF-1/OPG/RANKL/CTSK signaling pathway. This study provides new insights for the study of short stature and bone injury caused by F-53B.


Asunto(s)
Desarrollo Óseo , Lactancia , Exposición Materna , Ratones Endogámicos C57BL , Efectos Tardíos de la Exposición Prenatal , Animales , Femenino , Masculino , Embarazo , Ratones , Exposición Materna/efectos adversos , Desarrollo Óseo/efectos de los fármacos , Factor I del Crecimiento Similar a la Insulina/metabolismo , Fluorocarburos/toxicidad , Osteoprotegerina/metabolismo , Osteoclastos/efectos de los fármacos , Huesos/efectos de los fármacos , Osteoblastos/efectos de los fármacos , Ácidos Sulfónicos/toxicidad
14.
J Cell Biol ; 223(7)2024 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-38717338

RESUMEN

Senataxin is an evolutionarily conserved RNA-DNA helicase involved in DNA repair and transcription termination that is associated with human neurodegenerative disorders. Here, we investigated whether Senataxin loss affects protein homeostasis based on previous work showing R-loop-driven accumulation of DNA damage and protein aggregates in human cells. We find that Senataxin loss results in the accumulation of insoluble proteins, including many factors known to be prone to aggregation in neurodegenerative disorders. These aggregates are located primarily in the nucleolus and are promoted by upregulation of non-coding RNAs expressed from the intergenic spacer region of ribosomal DNA. We also map sites of R-loop accumulation in human cells lacking Senataxin and find higher RNA-DNA hybrids within the ribosomal DNA, peri-centromeric regions, and other intergenic sites but not at annotated protein-coding genes. These findings indicate that Senataxin loss affects the solubility of the proteome through the regulation of transcription-dependent lesions in the nucleus and the nucleolus.


Asunto(s)
ADN Helicasas , Enzimas Multifuncionales , ARN Helicasas , ARN no Traducido , Humanos , Nucléolo Celular/metabolismo , Nucléolo Celular/genética , Daño del ADN , ADN Helicasas/metabolismo , ADN Helicasas/genética , ADN Ribosómico/genética , ADN Ribosómico/metabolismo , Enzimas Multifuncionales/metabolismo , Enzimas Multifuncionales/genética , Agregado de Proteínas , Proteostasis , Estructuras R-Loop/genética , ARN Helicasas/metabolismo , ARN Helicasas/genética , ARN no Traducido/genética , ARN no Traducido/metabolismo
15.
Ecotoxicol Environ Saf ; 277: 116399, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38677070

RESUMEN

Perfluoroalkyl and polyfluoroalkyl substances (PFASs), as pollutants, can cause palpable environmental and health impacts around the world, as endocrine disruptors, can disrupt endocrine homeostasis and increase the risk of diseases. Chlorinated polyfluoroalkyl ether sulfonate (F-53B), as a substitute for PFAS, was determined to have potential toxicity. Puberty is the stage when sexual organs develop and hormones change dramatically, and abnormal uterine development can increase the risk of uterine lesions and lead to infertility. This study was designed to explore the impact of F-53B on uterine development during puberty. Four-week-old female SD rats were exposed to 0.125 and 6.25 mg/L F-53B during puberty. The results showed that F-53B interfered with growth and sex hormone levels and bound to oestrogen-related receptors, which affected their function, contributed to the accumulation of reactive oxygen species, promoted cell apoptosis and inhibited cell proliferation, ultimately causing uterine dysplasia.


Asunto(s)
Alcanosulfonatos , Apoptosis , Disruptores Endocrinos , Especies Reactivas de Oxígeno , Maduración Sexual , Útero , Animales , Femenino , Ratas , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Disruptores Endocrinos/toxicidad , Contaminantes Ambientales/toxicidad , Fluorocarburos/toxicidad , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno/metabolismo , Receptores de Estrógenos/metabolismo , Maduración Sexual/efectos de los fármacos , Útero/efectos de los fármacos , Alcanosulfonatos/toxicidad
16.
Environ Toxicol ; 39(6): 3314-3329, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38440912

RESUMEN

BACKGROUND: Previous studies on the effects of microplastics (MPs) on bone in early development are limited. This study aimed to investigate the adverse effects of MPs on bone in young rats and the potential mechanism. METHODS: Three-week-old female rats were orally administered MPs for 28 days, and endoplasmic reticulum (ER) stress inhibitor salubrinal (SAL) and ER stress agonist tunicamycin (TM) were added to evaluate the effect of ER stress on toxicity of MPs. The indicators of growth and plasma markers of bone turnover were evaluated. Tibias were analyzed using micro-computed tomography (micro-CT). Histomorphological staining of growth plates was performed, and related gene expression of growth plate chondrocytes was tested. RESULTS: After exposure of MPs, the rats had decreased growth, shortened tibial length, and altered blood calcium and phosphorus metabolism. Trabecular bone was sparse according to micro-CT inspection. In the growth plate, the thickness of proliferative zone substantial reduced while the thickness of hypertrophic zone increased significantly, and the chondrocytes were scarce and irregularly arranged according to tibial histological staining. The transcription of the ER stress-related genes BIP, PERK, ATF4, and CHOP dramatically increased, and the transcription factors involved in chondrocyte proliferation, differentiation, apoptosis, and matrix secretion were aberrant according to RT-qPCR and western blotting. Moreover, the addition of TM showed higher percentage of chondrocyte death. Administration of SAL alleviated all of the MPs-induced symptoms. CONCLUSION: These results indicated that MPs could induce growth retardation and longitudinal bone damage in early development. The toxicity of MPs may attribute to induced ER stress and impaired essential processes of the endochondral ossification after MPs exposure.


Asunto(s)
Estrés del Retículo Endoplásmico , Placa de Crecimiento , Microplásticos , Poliestirenos , Animales , Estrés del Retículo Endoplásmico/efectos de los fármacos , Placa de Crecimiento/efectos de los fármacos , Placa de Crecimiento/patología , Femenino , Ratas , Microplásticos/toxicidad , Poliestirenos/toxicidad , Ratas Sprague-Dawley , Osteogénesis/efectos de los fármacos , Condrocitos/efectos de los fármacos , Tibia/efectos de los fármacos , Tibia/patología
17.
Biosens Bioelectron ; 255: 116244, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38547644

RESUMEN

The huge economic loss and threat to human health caused by bacterial infection have attracted the public's concern, and there is an urgent need to relieve and improve the tough problem. Therefore, it is significant to establish a facile, rapid, and sensitive method for bacterial detection considering the shortcomings of existing methods. Förster resonance energy transfer (FRET)-based sensors have exhibited immense potential and applicability for bacterial detection given their high signal-to-noise ratio and high sensitivity. This review focuses on the development of FRET-based fluorescence assays for bacterial detection. We summarize the principle of FRET-based assays, discuss the commonly used recognition molecules and further introduce three frequent construction strategies. Based on the strategies and materials, relevant applications are presented. Moreover, some restrictions of FRET fluorescence sensors and development prospects are discussed. Suitable donor-acceptor pairs and stable recognition molecules are the essential conditions for sensors to play their roles, and there is still some room for development. Besides, applying FRET fluorescence sensors to point-of-care detection is still difficult. Future developments could focus on near-infrared fluorescent dyes and simultaneous detection of multiple analytes.


Asunto(s)
Técnicas Biosensibles , Transferencia Resonante de Energía de Fluorescencia , Humanos , Transferencia Resonante de Energía de Fluorescencia/métodos , Colorantes Fluorescentes
18.
Colloids Surf B Biointerfaces ; 237: 113868, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38522282

RESUMEN

Silver nanoparticles (AgNPs) is an excellent antibacterial agent, which is widely used in medical, food, environmental and other fields, but AgNPs are easy to accumulate in aqueous solution, so their application in various fields is limited. Therefore, it is particularly important to propose a new application method or to prepare a new composite material. In this study, OA/PVA was obtained by cross-linking oxalic acid (OA) with polyvinyl alcohol (PVA). Then Ag/NCC was obtained by in situ reduction of AgNPs on nanocellulose crystals (NCC). Finally, Ag/NCC/OA/PVA composite antimicrobial films with good waterproofing effect were prepared by mixing Ag/NCC with OA/PVA. Subsequently, the films were characterized using SEM, UV-vis, FTIR and XRD, as well as physicochemical properties such as mechanical strength and hydrophilic properties were determined. The results indicated that the Ag/NCC/OA/PVA films possess good light transmittance, mechanical properties, water resistance, antibacterial activity, and biodegradability. The results of the mechanism study showed that Ag/NCC/OA/PVA films can destroy cell integrity, inhibit succinate dehydrogenase (SDH) activity, thereby reducing intracellular ATP levels. And induce a large number of reactive oxygen species (ROS) production, eventually leading to the death of C. sakazakii. In summary, Ag/NCC/OA/PVA film has good physical and chemical properties, antibacterial activity and biocompatibility, and has promising applications in food and medical antibacterial fields.


Asunto(s)
Antiinfecciosos , Nanopartículas del Metal , Plata/farmacología , Plata/química , Alcohol Polivinílico/química , Nanopartículas del Metal/química , Ácido Oxálico/farmacología , Escherichia coli , Staphylococcus aureus , Antibacterianos/farmacología , Antibacterianos/química , Antiinfecciosos/farmacología , Biopelículas
19.
Int J Pharm ; 654: 123968, 2024 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-38460771

RESUMEN

Wound healing constitutes a formidable challenge within the healthcare system, attributable to infection risks and protracted recovery periods. The pressing need for innovative wound healing methods has spurred the urgency to develop novel approaches. This study sought to advance wound healing by introducing a novel approach employing a composite sponge dressing. The composite sponge dressing, derived from LFL-ZnO (synthesized through the green methodology utilizing Lactobacillus plantarum ZDY2013 fermentation liquid), polyvinyl alcohol (PVA), and sodium alginate (SA) via a freeze-thaw cycle and freeze-drying molding process, demonstrated notable properties. The findings elucidate the commendable swelling, moisturizing, and mechanical attributes of the SA/LFL-ZnO/PVA composite sponge dressing, characterized by a porous structure. Remarkably, the dressing incorporating LFL-ZnO exhibited substantial inhibition against both methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus aureus (S. aureus). Hemolysis and cytotoxicity tests corroborated the excellent biocompatibility of the sponge dressing. In vivo evaluation of the therapeutic efficacy of the 1 mg/mL LFL-ZnO composite dressing on scald wounds and S. aureus-infected wounds revealed its capacity to accelerate wound healing and exert pronounced antibacterial effects. Consequently, the composite sponge dressings synthesized in this study hold significant potential for application in wound treatment.


Asunto(s)
Staphylococcus aureus Resistente a Meticilina , Óxido de Zinc , Alcohol Polivinílico/química , Óxido de Zinc/química , Staphylococcus aureus , Alginatos/química , Vendajes/microbiología , Antibacterianos/farmacología , Antibacterianos/química , Hidrogeles/química , Cicatrización de Heridas
20.
Anal Methods ; 16(12): 1763-1769, 2024 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-38450684

RESUMEN

Development of combined mass spectrometry ionization sources has enabled expansion of the application and scope of mass spectrometry. A novel hybrid ionization system combining vacuum ultraviolet (VUV) and atmospheric pressure chemical ionization (APCI) was constructed. Gaseous samples were self-aspirated into an ionization zone through a capillary by negative pressure, generated by high-speed airflow based on the Venturi effect. Compared with APCI mode alone, the signal-to-noise ratio (S/N) in APCI/VUV mode was increased by about 276-times. To increase the ionization efficiency further, correlated experimental conditions were optimized. Four types of volatile organic compounds (VOCs) were tested to evaluate the performance of the APCI/VUV ion source. Excellent linearity and limit of detection were achieved for compounds in mixed solutions. Quantitative analyses of four VOCs (toluene, cyclohexanone, styrene and ethylbenzene) using APCI/VUV-MS were done, and the relative standard deviations (RSDs) were 1.57%, 6.30%, 4.49% and 8.21%, respectively, indicating that the APCI/VUV ionization source had excellent reproducibility. Our results demonstrated that the developed method was promising for analyzing VOCs as well as being rapid, simple, and easy to operate.

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