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1.
J Hazard Mater ; 472: 134571, 2024 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-38743976

RESUMEN

Research on riverine microplastics has gradually increased, highlighting an area for further exploration: the lack of extensive, large-scale regional variations analysis due to methodological and spatiotemporal limitations. Herein, we constructed and applied a comprehensive framework for synthesizing and analyzing literature data on riverine microplastics to enable comparative research on the regional variations on a large scale. Research results showed that in 76 rivers primarily located in Asia, Europe, and North America, the microplastic abundance of surface water in Asian rivers was three times higher than that in Euro-America rivers, while sediment in Euro-American rivers was five times more microplastics than Asia rivers, indicating significant regional variations (p < 0.001). Additionally, based on the income levels of countries, rivers in lower-middle and upper-middle income countries had significantly (p < 0.001) higher abundance of microplastics in surface water compared to high-income countries, while the opposite was true for sediment. This phenomenon was preliminarily attributed to varying levels of urbanization across countries. Our proposed framework for synthesizing and analyzing microplastic literature data provides a holistic understanding of microplastic disparities in the environment, and can facilitate broader discussions on management and mitigation strategies.

2.
Am J Clin Nutr ; 2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38729573

RESUMEN

BACKGROUND: Long-chain free fatty acids (FFAs) are associated with risk of incident diabetes. However, comprehensive assessment of the associations in normoglycemic populations is lacking. OBJECTIVE: Our study aims to comprehensively investigate the prospective associations and patterns of FFA profiles with diabetes risk among normoglycemic Chinese adults. METHODS: This is a prospective nested case-control study from the China Cardiometabolic Disease and Cancer Cohort (4C) study. We quantitatively measured 53 serum FFAs using targeted metabolomics approach in 1707 incident diabetes subjects and 1707 propensity score-matched normoglycemic controls. Conditional logistic regression models were employed to estimate odds ratios (ORs) for associations. Least Absolute Shrinkage and Selection Operator (LASSO) penalty regression and quantile g-computation (qg-comp) analyses were implemented to estimate the association between multi-FFA exposures and incident diabetes. RESULTS: The majority of odd-chain FFAs exhibited an inverse association with incident diabetes, wherein the ORs per SD increment of all 7 saturated fatty acids (SFAs), monounsaturated fatty acid (MUFA) 15:1 and polyunsaturated fatty acid (PUFA) 25:2 were ranging from 0.79 to 0.88 (95%CIs ranging between 0.71 and 0.97). Even-chain FFAs comprised 99.3% of total FFAs and displayed heterogeneity with incident diabetes. SFAs with 18 to 26 carbon atoms are inversely linked to incident diabetes, with ORs ranging from 0.81 to 0.86 (95%CIs ranging between 0.73 and 0.94). MUFAs 26:1 (OR[95%CI]: 0.85[0.76-0.94]), PUFAs 20:4 (0.84[0.75-0.94]) and 24:2 (0.87[0.78-0.97]) demonstrated significant associations. In multi-FFA exposure model, 24 FFAs were significantly associated with incident diabetes, most of which were consistent with univariate results. The mixture OR was 0.78 [0.61-0.99] (P= 0.04159). Differential correlation network analysis revealed pre-existing perturbations in intraclass and interclass FFA coregulation before diabetes onset. CONCLUSIONS: These findings underscore the variations in diabetes risk associated with FFAs across chain length and unsaturation degree, highlighting the importance of recognizing FFA subtypes in the pathogenesis of diabetes.

3.
J Mol Cell Biol ; 2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38740522

RESUMEN

The mammary gland is a dynamic organ that undergoes significant changes at multiple stages of postnatal development. Although the roles of systemic hormones and microenvironmental cues in mammary homeostasis have been extensively studied, the influence of neural signals, particularly those from the sympathetic nervous system, remains poorly understood. Here, using a mouse mammary gland model, we delved into the regulatory role of sympathetic nervous signaling in the context of mammary stem cells and mammary development. Our findings revealed that depletion of sympathetic nerve signals results in defective mammary development during puberty, adulthood, and pregnancy, accompanied by a reduction in mammary stem cell number. Through in vitro three-dimensional culture and in vivo transplantation analyses, we demonstrated that the absence of sympathetic nerve signals hinders mammary stem cell self-renewal and regeneration, while activation of sympathetic nervous signaling promotes these capacities. Mechanistically, sympathetic nerve signals orchestrate mammary stem cell activity and mammary development through the ERK signaling pathway. Collectively, our study unveils the crucial roles of sympathetic nerve signals in sustaining mammary development and regulating mammary stem cell activity, offering a novel perspective on the involvement of the nervous system in modulating adult stem cell function and organ development.

4.
Nat Hum Behav ; 2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38740987
5.
J Vis Exp ; (207)2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38767369

RESUMEN

A total of five samples of Chrysomya megacephala samples - three fresh samples, one sample stored in alcohol for 2 years, and one sample stored in dry sealed storage for 2 years protected from light only - were selected to investigate whether a blood DNA extraction kit could extract DNA from necrophilous flies and to determine whether alcohol could prolong the preservation of necrophilous flies' DNA. First, the blood DNA extraction kit was used to extract DNA from their thorax tissues. Then, the DNA purity and concentration were examined using a microplate reader and a fluorometer. Finally, PCR amplification and electrophoresis of the extracted DNA were done with necrophilic fly-specific primers located in the mitochondrial CO I gene sequence. The results showed that the DNA purity of all samples was greater than 2.0. The DNA concentration was observed to be of the following order: fresh samples > alcohol-preserved old samples > untreated, old samples. All samples had specific electrophoretic bands after PCR amplification. In conclusion, a blood DNA extraction kit can be used to extract DNA from necrophilic flies successfully, and the DNA concentration of fresh fly samples is greater than that of old fly samples. The flies can be stored in alcohol for a long time.


Asunto(s)
ADN , Reacción en Cadena de la Polimerasa , Animales , ADN/aislamiento & purificación , ADN/genética , Reacción en Cadena de la Polimerasa/métodos , Calliphoridae/genética , Calliphoridae/química
6.
Sci Rep ; 14(1): 11474, 2024 05 20.
Artículo en Inglés | MEDLINE | ID: mdl-38769356

RESUMEN

This study investigated the correlation of newly identified inflammatory and insulin resistance indices with cerebral amyloid angiopathy (CAA), and explored their potential to differentiate CAA from hypertensive arteriopathy (HA). We retrospectively analyzed 514 consecutive patients with cerebral small vessel disease (CSVD)-related haemorrhage, comparing the differences in novel inflammatory and insulin resistance indices between patients with CAA and HA. Univariate regression, LASSO and multivariate regression were used to screen variables and construct a classification diagnosis nomogram. Additionally, these biomarkers were explored in patients with mixed haemorrhagic CSVD. Inflammatory indices were higher in CAA patients, whereas insulin resistance indices were higher in HA patients. Further analysis identified neutrophil-to-lymphocyte ratio (NLR, OR 1.17, 95% CI 1.07-1.30, P < 0.001), and triglyceride-glucose index (TyG, OR = 0.56, 95% CI 0.36-0.83, P = 0.005) as independent factors for CAA. Therefore, we constructed a CAA prediction nomogram without haemorrhagic imaging markers. The nomogram yielded an area under the curve (AUC) of 0.811 (95% CI 0.764-0.865) in the training set and 0.830 (95% CI 0.718-0.887) in the test set, indicating an ability to identify high-risk CAA patients. These results show that CSVD patients can be phenotyped using novel inflammatory and insulin resistance indices, potentially allowing identification of high-risk CAA patients without haemorrhagic imaging markers.


Asunto(s)
Biomarcadores , Angiopatía Amiloide Cerebral , Inflamación , Resistencia a la Insulina , Humanos , Masculino , Femenino , Angiopatía Amiloide Cerebral/patología , Anciano , Estudios Retrospectivos , Biomarcadores/sangre , Inflamación/patología , Persona de Mediana Edad , Neutrófilos/metabolismo , Enfermedades de los Pequeños Vasos Cerebrales/patología , Enfermedades de los Pequeños Vasos Cerebrales/sangre , Nomogramas , Linfocitos/metabolismo , Triglicéridos/sangre
7.
Cancers (Basel) ; 16(9)2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38730567

RESUMEN

(1) Background: The research group has developed a new small molecule, 6-Isopropyldithio-2'-deoxyguanosine analogs-YLS004, which has been shown to be the most sensitive in acute T-lymphoblastic leukemia cells. Moreover, it was found that the structure of Nelarabine, a drug used to treat acute T-lymphoblastic leukemia, is highly similar to that of YLS004. Consequently, the structure of YLS004 was altered to produce a new small molecule inhibitor for this study, named YLS010. (2) Results: YLS010 has exhibited potent anti-tumor effects by inducing cell apoptosis and ferroptosis. A dose gradient was designed for in vivo experiments based on tentative estimates of the toxicity dose using acute toxicity in mice and long-term toxicity in rats. The study found that YLS010 at a dose of 8 mg/kg prolonged the survival of late-stage acute T-lymphoblastic leukemia mice in the mouse model study. (3) Conclusions: YLS010 has demonstrated specific killing effects against acute T-lymphoblastic leukemia both in vivo and in vitro. Preclinical studies of YLS010 offer a new opportunity for the treatment of patients with acute T-lymphoblastic leukemia in clinical settings.

9.
Cancer Med ; 13(10): e7233, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38752474

RESUMEN

BACKGROUND: Over the past decade, immune checkpoint inhibitors (ICIs) have significantly transformed cancer treatment. However, ICIs inevitably may cause a spectrum of immune-related adverse events, among which cardiovascular toxicity, particularly myocarditis, while infrequent, has garnered increasing attention due to its high fatality rate. METHODS: We conducted a multicenter retrospective study to characterize ICI-associated cardiovascular adverse events. Logistic regression was performed to explore the risk factors for the development of myocarditis and severe myocarditis. Receiver operating characteristic curves were conducted to assess the diagnostic abilities of cardiac biomarkers to distinguish different cardiovascular toxicities, and the performance and calibration were evaluated using Hosmer-Lemeshow test. RESULTS: Forty-four patients were identified, including thirty-five myocarditis, five heart failure, three arrhythmias, and one myocardial infarction. Compared with other patients, myocarditis patients had higher cardiac troponin-I (cTnI) levels (p < 0.001), higher creatine kinase levels (p = 0.003), higher creatine kinase isoenzyme-MB (CK-MB) levels (p = 0.013), and shorter time to the incidence of adverse cardiovascular events (p = 0.022) after ICI treatment. Twenty-one patients (60%) were classified as severe myocarditis, and they presented higher cardiac troponin I (cTnI) levels (p = 0.013), higher N-terminal pro-B-type natriuretic peptide levels (p = 0.031), higher creatine kinase levels (p = 0.018), higher CK-MB levels (p = 0.026), and higher neutrophil to lymphocyte ratio (NLR) levels (p = 0.016) compared to non-severe myocarditis patients after ICI treatment. Multivariate logistic regression showed that CK-MB (adjusted odds ratio [OR]: 1.775, 95% confidence interval [CI]: 1.055-2.984, p = 0.031) was the independent risk factor of the development of ICI-associated myocarditis, and cTnI (adjusted OR: 1.021, 95% CI: 1.002-1.039, p = 0.03) and NLR (adjusted OR: 1.890, 95% CI: 1.026-3.483, p = 0.041) were the independent risk factors of ICI-associated severe myocarditis. The receiver operating characteristic curve showed an area under curve of 0.785 (95% CI: 0.642 to 0.928, p = 0.013) for CK-MB, 0.765 (95% CI: 0.601 to 0.929, p = 0.013) for cTnI, and 0.773 for NLR (95% CI: 0.597 to 0.948, p = 0.016). CONCLUSIONS: Elevated CK-MB after ICI treatment is the independent risk factor for the incidence of ICI-associated myocarditis, and elevated cTnI and NLR after ICI treatment are the independent risk factors for the development of ICI-associated severe myocarditis. CK-MB, cTnI, and NLR demonstrated a promising predictive utility for the identification of ICI-associated myocarditis and severe myocarditis.


Asunto(s)
Inhibidores de Puntos de Control Inmunológico , Miocarditis , Humanos , Masculino , Estudios Retrospectivos , Femenino , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Miocarditis/inducido químicamente , Miocarditis/epidemiología , Miocarditis/diagnóstico , Persona de Mediana Edad , Anciano , Factores de Riesgo , Biomarcadores/sangre , Neoplasias/tratamiento farmacológico , Troponina I/sangre , Curva ROC , Enfermedades Cardiovasculares/inducido químicamente , Enfermedades Cardiovasculares/epidemiología , Forma MB de la Creatina-Quinasa/sangre , Péptido Natriurético Encefálico/sangre , Insuficiencia Cardíaca/inducido químicamente
10.
IEEE Trans Cybern ; PP2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38713577

RESUMEN

State responses for several classes of linear systems are investigated in this article. The involved systems include state-delayed linear systems, and high-order linear systems. At first, the single-fundamental-matrix-based approach is extended to these systems, and their state responses are expressed by their fundamental matrices (FMs). In addition, the multiple-FMs-based approach is presented for these systems. Based on a group of FMs, the state responses for the considered time-invariant systems are derived. For the considered time-variant systems, their state responses are explicitly expressed by their transition matrices. As an application of the fundamental-matrix-based approach, a stabilizing control law is designed for a class of high-order fully actuated continuous-time linear systems with a single input-delay.

11.
medRxiv ; 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38699308

RESUMEN

Blood cell phenotypes are routinely tested in healthcare to inform clinical decisions. Genetic variants influencing mean blood cell phenotypes have been used to understand disease aetiology and improve prediction; however, additional information may be captured by genetic effects on observed variance. Here, we mapped variance quantitative trait loci (vQTL), i.e. genetic loci associated with trait variance, for 29 blood cell phenotypes from the UK Biobank (N~408,111). We discovered 176 independent blood cell vQTLs, of which 147 were not found by additive QTL mapping. vQTLs displayed on average 1.8-fold stronger negative selection than additive QTL, highlighting that selection acts to reduce extreme blood cell phenotypes. Variance polygenic scores (vPGSs) were constructed to stratify individuals in the INTERVAL cohort (N~40,466), where genetically less variable individuals (low vPGS) had increased conventional PGS accuracy (by ~19%) than genetically more variable individuals. Genetic prediction of blood cell traits improved by ~10% on average combining PGS with vPGS. Using Mendelian randomisation and vPGS association analyses, we found that alcohol consumption significantly increased blood cell trait variances highlighting the utility of blood cell vQTLs and vPGSs to provide novel insight into phenotype aetiology as well as improve prediction.

12.
Nat Commun ; 15(1): 4031, 2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38740772

RESUMEN

The rapid global distribution of COVID-19 vaccines, with over a billion doses administered, has been unprecedented. However, in comparison to most identified clinical determinants, the implications of individual genetic factors on antibody responses post-COVID-19 vaccination for breakthrough outcomes remain elusive. Here, we conducted a population-based study including 357,806 vaccinated participants with high-resolution HLA genotyping data, and a subset of 175,000 with antibody serology test results. We confirmed prior findings that single nucleotide polymorphisms associated with antibody response are predominantly located in the Major Histocompatibility Complex region, with the expansive HLA-DQB1*06 gene alleles linked to improved antibody responses. However, our results did not support the claim that this mutation alone can significantly reduce COVID-19 risk in the general population. In addition, we discovered and validated six HLA alleles (A*03:01, C*16:01, DQA1*01:02, DQA1*01:01, DRB3*01:01, and DPB1*10:01) that independently influence antibody responses and demonstrated a combined effect across HLA genes on the risk of breakthrough COVID-19 outcomes. Lastly, we estimated that COVID-19 vaccine-induced antibody positivity provides approximately 20% protection against infection and 50% protection against severity. These findings have immediate implications for functional studies on HLA molecules and can inform future personalised vaccination strategies.


Asunto(s)
Alelos , Anticuerpos Antivirales , Vacunas contra la COVID-19 , COVID-19 , Antígenos HLA , Polimorfismo de Nucleótido Simple , SARS-CoV-2 , Humanos , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , COVID-19/inmunología , COVID-19/prevención & control , COVID-19/genética , COVID-19/virología , SARS-CoV-2/inmunología , SARS-CoV-2/genética , Anticuerpos Antivirales/inmunología , Anticuerpos Antivirales/sangre , Antígenos HLA/genética , Antígenos HLA/inmunología , Formación de Anticuerpos/genética , Formación de Anticuerpos/inmunología , Masculino , Femenino , Genotipo , Vacunación , Persona de Mediana Edad , Adulto , Variación Genética , Cadenas beta de HLA-DQ/genética , Cadenas beta de HLA-DQ/inmunología , Infección Irruptiva
13.
Ecol Evol ; 14(5): e11426, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38746544

RESUMEN

Examining beta diversity of animal assemblages in fragmented habitats, which measures variation in species composition among different fragments, is important for understanding the impact of habitat fragmentation on biodiversity. However, relying solely on taxonomic composition may not provide a comprehensive understanding. Incorporating measures of functional and phylogenetic diversities is essential for elucidating the ecological mechanisms underlying changes in community composition. In addition, prevailing studies often prioritize the evaluation of landscape characteristics within fragments as determinants of beta diversity, neglecting differences in habitat type and plant community composition. In this study, we surveyed birds in 26 remnant woodlot patches (ranging from 0.3 to 290.4 ha) in an urban landscape, southwest China, during the breeding season from 2017 to 2022. We recorded 70 bird species (excluding those recorded only once and high-flying birds, including raptors, swallows, and swifts), with the number of species per patch varying from 14 to 56. The overall bird taxonomic and phylogenetic beta diversities were primarily contributed by the turnover component, while functional beta diversity was dominated by the nestedness-resultant component. Patch area and perimeter area ratio significantly influenced the taxonomic, functional, and phylogenetic beta diversities, primarily mediated through the nestedness-resultant component, while inter-patch distance had a significant effect via the turnover component. In addition, there was a considerable correlation of bird taxonomic, functional, and phylogenetic beta diversities with habitat type and woody plant beta diversities, including their respective partitioned turnover and nestedness-resultant components. Our results suggest that bird assemblages in these patches may be regulated by selective extinction, interspecific competition, and environmental filtering. The findings have significant implications for sustainable landscape planning and habitat restoration. Conserving habitat patches of different sizes and maintaining or enhancing habitat heterogeneity between patches can facilitate the persistence of metacommunities.

14.
Front Neurosci ; 18: 1309684, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38576865

RESUMEN

The loss of dopaminergic neurons in the substantia nigra and the abnormal accumulation of synuclein proteins and neurotransmitters in Lewy bodies constitute the primary symptoms of Parkinson's disease (PD). Besides environmental factors, scholars are in the early stages of comprehending the genetic factors involved in the pathogenic mechanism of PD. Although genome-wide association studies (GWAS) have unveiled numerous genetic variants associated with PD, precisely pinpointing the causal variants remains challenging due to strong linkage disequilibrium (LD) among them. Addressing this issue, expression quantitative trait locus (eQTL) cohorts were employed in a transcriptome-wide association study (TWAS) to infer the genetic correlation between gene expression and a particular trait. Utilizing the TWAS theory alongside the enhanced Joint-Tissue Imputation (JTI) technique and Mendelian Randomization (MR) framework (MR-JTI), we identified a total of 159 PD-associated genes by amalgamating LD score, GTEx eQTL data, and GWAS summary statistic data from a substantial cohort. Subsequently, Fisher's exact test was conducted on these PD-associated genes using 5,152 differentially expressed genes sourced from 12 PD-related datasets. Ultimately, 29 highly credible PD-associated genes, including CTX1B, SCNA, and ARSA, were uncovered. Furthermore, GO and KEGG enrichment analyses indicated that these genes primarily function in tissue synthesis, regulation of neuron projection development, vesicle organization and transportation, and lysosomal impact. The potential PD-associated genes identified in this study not only offer fresh insights into the disease's pathophysiology but also suggest potential biomarkers for early disease detection.

15.
Food Chem ; 448: 139167, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-38574718

RESUMEN

Cyclodextrin-based metal-organic framework (CD-MOF) has been widely used in various delivery systems due to its excellent edibility and high drug loading capacity. However, its typically bulky size and high brittleness in aqueous solutions pose significant challenges for practical applications. Here, we proposed an ultrasonic-assisted method for rapid synthesis of uniformly-sized nanoscale CD-MOF, followed by its hydrophobic modification through ester bond cross-linking (Nano-CMOF). Proper ultrasound treatment effectively reduced particle size to nanoscale (393.14 nm). Notably, carbonate ester cross-linking method significantly improved water stability without altering its cubic shape and high porosity (1.3 cm3/g), resulting in a retention rate exceeding 90% in various media. Furthermore, the loading of quercetin did not disrupt cubic structure and showcased remarkable storage stability. Nano-CMOF achieved controlled release of quercetin in both aqueous environments and digestion. Additionally, Nano-CMOF demonstrated exceptional antioxidant (free radical scavenging 82.27%) and biocompatibility, indicating its significant potential as novel nutritional delivery systems in food and biomedical fields.


Asunto(s)
Ciclodextrinas , Preparaciones de Acción Retardada , Portadores de Fármacos , Interacciones Hidrofóbicas e Hidrofílicas , Estructuras Metalorgánicas , Quercetina , Quercetina/química , Estructuras Metalorgánicas/química , Ciclodextrinas/química , Portadores de Fármacos/química , Preparaciones de Acción Retardada/química , Nanopartículas/química , Materiales Biocompatibles/química , Tamaño de la Partícula , Humanos , Estabilidad de Medicamentos
16.
J Ethnopharmacol ; 331: 118265, 2024 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-38677579

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese Medicines (TCMs) have emerged as a promising complementary therapy in the management of prostate cancer (PCa), particularly in addressing resistance to Docetaxel (DTX) chemotherapy. AIM OF THE REVIEW: This review aims to elucidate the mechanisms underlying the development of resistance to DTX in PCa and explore the innovative approach of integrating TCMs in PCa treatment to overcome this resistance. Key areas of investigation include alterations in microtubule proteins, androgen receptor and androgen receptor splice variant 7, ERG rearrangement, drug efflux mechanisms, cancer stem cells, centrosome clustering, upregulation of the PI3K/AKT signaling pathway, enhanced DNA damage repair capability, and the involvement of neurotrophin receptor 1/protein kinase C. MATERIALS AND METHODS: With "Prostate cancer", "Docetaxel", "Docetaxel resistance", "Natural compounds", "Traditional Chinese medicine", "Traditional Chinese medicine compound", "Medicinal plants" as the main keywords, PubMed, Web of Science and other online search engines were used for literature retrieval. RESULTS: Our findings underscore the intricate interplay of molecular alterations that collectively contribute to the resistance of PCa cells to DTX. Moreover, we highlight the potential of TCMs as a promising complementary therapy, showcasing their ability to counteract DTX resistance and enhance therapeutic efficacy. CONCLUSION: The integration of TCMs in PCa treatment emerges as an innovative approach with significant potential to overcome DTX resistance. This review not only provides insights into the mechanisms of resistance but also presents new prospects for improving the clinical outcomes of patients with PCa undergoing DTX therapy. The comprehensive understanding of these mechanisms lays the foundation for future research and the development of more effective therapeutic interventions.

17.
Biomed Pharmacother ; 174: 116548, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38599064

RESUMEN

BACKGROUND: Various heart diseases ultimately lead to chronic heart failure (CHF). In CHF, the inflammatory response is associated with pyroptosis, which is mediated by the NOD-like receptor protein 3 (NLRP3) inflammasome. Fu Xin decoction (FXD) is commonly used in clinical practice to treat CHF and improve inflammatory conditions. However, the specific pharmacological mechanisms of action for FXD in these processes have yet to be fully understood. PURPOSE: The objective of this study was to examine the protective mechanism of FXT against CHF, both in H9c2 cells and mice. METHOD: A CHF mouse model was established, and the effect of FXD was observed via gavage. Cardiac function was evaluated using echocardiography, while serum BNP and LDH levels were analyzed to assess the severity of CHF. Hematoxylin and eosin staining (H&E) and Masson staining were performed to evaluate myocardial pathological changes, and TdT-mediated dUTP Nick-End Labeling staining was used to detect DNA damage. Additionally, doxorubicin was utilized to induce myocardial cell injury in H9c2 cells, establishing a relevant model. CCK8 was used to observe cell viability and detect LDH levels in the cell supernatant. Subsequently, the expression of pyroptosis-related proteins was detected using immunohistochemistry, immunofluorescence, and western blotting. Finally, the pharmacological mechanism of FXD against CHF was further validated by treating H9c2 cells with an NLRP3 activator and inducing NLRP3 overexpression. RESULT: According to current research findings, echocardiography demonstrated a significant improvement of cardiac function by FXD, accompanied by reduced levels of BNP and LDH, indicating the amelioration of cardiac injury in CHF mice. FXD exhibited the ability to diminish serum CRP and MCP inflammatory markers in CHF mice. The results of HE and Masson staining analyses revealed a significant reduction in pathological damage of the heart tissue following FXD treatment. The CCK8 assay demonstrated the ability of FXD to enhance H9c2 cell viability, improve cell morphology, decrease LDH levels in the cell supernatant, and alleviate cell damage. Immunohistochemistry, Western blotting, and immunofluorescence staining substantiated the inhibitory effect of FXD on the NLRP3/caspase-1/GSDMD pyroptosis signaling pathway in both CHF and H9c2 cell injury models. Ultimately, the administration of the NLRP3 activator (Nigericin) and the overexpression of NLRP3 counteract the effects of FXD on cardiac protection and pyroptosis inhibition in vitro. CONCLUSION: FXD exhibits a cardioprotective effect, improving CHF and alleviating pyroptosis by inhibiting the NLRP3/caspase-1/GSDMD pathway.


Asunto(s)
Medicamentos Herbarios Chinos , Insuficiencia Cardíaca , Proteína con Dominio Pirina 3 de la Familia NLR , Piroptosis , Animales , Ratones , Caspasa 1/efectos de los fármacos , Caspasa 1/metabolismo , Línea Celular , Enfermedad Crónica , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos/farmacología , Gasderminas/efectos de los fármacos , Gasderminas/metabolismo , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/metabolismo , Inflamasomas/metabolismo , Inflamasomas/efectos de los fármacos , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Ratones Endogámicos C57BL , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Proteína con Dominio Pirina 3 de la Familia NLR/efectos de los fármacos , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Proteínas de Unión a Fosfato/metabolismo , Piroptosis/efectos de los fármacos , Transducción de Señal/efectos de los fármacos
18.
Arch Endocrinol Metab ; 68: e230292, 2024 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-38652701

RESUMEN

Diabetic retinopathy (DR) is a complication of diabetes with a complex pathophysiology and multiple factors involved. Recently, it has been found that the upregulation of the renin-angiotensin-aldosterone system (RAAS) leads to overexpression of angiotensin II (Ang II), which induces oxidative stress, inflammation, and angiogenesis in the retina. Therefore, RAAS may be a promising therapeutic target in DR. Notably, RAAS inhibitors are often used in the treatment of hypertension. Still, the potential role and mechanism of DR must be further studied. In this review, we discuss and summarize the pathology and potential therapeutic goals of RAAS in DR.


Asunto(s)
Retinopatía Diabética , Sistema Renina-Angiotensina , Humanos , Retinopatía Diabética/tratamiento farmacológico , Retinopatía Diabética/fisiopatología , Sistema Renina-Angiotensina/fisiología , Sistema Renina-Angiotensina/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/fisiología , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Angiotensina II/fisiología , Animales
19.
Ann Hematol ; 103(6): 2165-2168, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38584216

RESUMEN

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive myeloid malignancy associated with a poor prognosis. Although allogeneic hematopoietic stem cell transplantation (allo-HSCT) has emerged as a potential treatment strategy for BPDCN, standardized conditioning regimens remain lacking. In this manuscript, we present two cases of BPDCN that were treated with a thiotepa-busulfan-fludarabine (TBF)-based conditioning regimen prior to allo-HSCT. Both cases demonstrated complete remission post-transplantation, sustained donor chimerism, and remission maintenance, suggesting the potential efficacy of the TBF conditioning regimen for BPDCN transplantation. Given the small sample size in our study, we emphasize caution and advocate for larger studies to confirm the efficacy of TBF in the treatment of BPDCN.


Asunto(s)
Busulfano , Células Dendríticas , Trasplante de Células Madre Hematopoyéticas , Tiotepa , Acondicionamiento Pretrasplante , Vidarabina , Humanos , Vidarabina/análogos & derivados , Vidarabina/administración & dosificación , Vidarabina/uso terapéutico , Acondicionamiento Pretrasplante/métodos , Células Dendríticas/patología , Tiotepa/administración & dosificación , Tiotepa/uso terapéutico , Masculino , Busulfano/administración & dosificación , Busulfano/uso terapéutico , Persona de Mediana Edad , Neoplasias Hematológicas/terapia , Neoplasias Hematológicas/patología , Femenino , Trasplante Homólogo , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Aloinjertos
20.
Food Funct ; 15(9): 4741-4762, 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38629635

RESUMEN

In the contemporary era, heightened emphasis on health and safety has emerged as a paramount concern among individuals with food. The concepts of "natural" and "green" have progressively asserted dominance in the food consumption market. Consequently, through continuous exploration and development, an escalating array of natural bioactive ingredients is finding application in both nutrition delivery and the broader food industry. Chlorogenic acid (CGA), a polyphenolic compound widely distributed in various plants in nature, has garnered significant attention. Abundant research underscores CGA's robust biological activity, showcasing notable preventive and therapeutic efficacy across diverse diseases. This article commences with a comprehensive overview, summarizing the dietary sources and primary biological activities of CGA. These encompass antioxidant, anti-inflammatory, antibacterial, anti-cancer, and neuroprotective activities. Next, a comprehensive overview of the current research on nutrient delivery systems incorporating CGA is provided. This exploration encompasses nanoparticle, liposome, hydrogel, and emulsion delivery systems. Additionally, the article explores the latest applications of CGA in the food industry. Serving as a cutting-edge theoretical foundation, this paper contributes to the design and development of CGA in the realms of nutrition delivery and the food industry. Finally, the article presents informed speculations and considerations for the future development of CGA.


Asunto(s)
Ácido Clorogénico , Industria de Alimentos , Ácido Clorogénico/química , Ácido Clorogénico/farmacología , Humanos , Animales , Antioxidantes/farmacología , Antioxidantes/química , Antiinflamatorios/farmacología , Antiinflamatorios/administración & dosificación , Antiinflamatorios/química , Sistemas de Liberación de Medicamentos/métodos
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