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1.
Biomaterials ; 313: 122775, 2025 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-39241549

RESUMEN

Acute Myocardial Infarction (AMI) has seen rising cases, particularly in younger people, leading to public health concerns. Standard treatments, like coronary artery recanalization, often don't fully repair the heart's microvasculature, risking heart failure. Advances show that Mesenchymal Stromal Cells (MSCs) transplantation improves cardiac function after AMI, but the harsh microenvironment post-AMI impacts cell survival and therapeutic results. MSCs aid heart repair via their membrane proteins and paracrine extracellular vesicles that carry microRNA-125b, which regulates multiple targets, preventing cardiomyocyte death, limiting fibroblast growth, and combating myocardial remodeling after AMI. This study introduces ultrasound-responsive phase-change bionic nanoparticles, leveraging MSCs' natural properties. These particles contain MSC membrane and microRNA-125b, with added macrophage membrane for stability. Using Ultrasound Targeted Microbubble Destruction (UTMD), this method targets the delivery of MSC membrane proteins and microRNA-125b to AMI's inflamed areas. This aims to enhance cardiac function recovery and provide precise, targeted AMI therapy.


Asunto(s)
Células Madre Mesenquimatosas , MicroARNs , Infarto del Miocardio , Nanopartículas , Infarto del Miocardio/terapia , Animales , Nanopartículas/química , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/citología , MicroARNs/metabolismo , MicroARNs/genética , Masculino , Recuperación de la Función , Trasplante de Células Madre Mesenquimatosas/métodos , Humanos , Materiales Biomiméticos/química , Materiales Biomiméticos/farmacología , Ratones , Microburbujas , Ondas Ultrasónicas
2.
Clin Med Insights Case Rep ; 17: 11795476241266395, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39282243

RESUMEN

Purpose: We report a case of a patient experiencing paroxysmal supraventricular tachycardia after infusing doxophylline. Methods: Clinical evaluations and the electrocardiogram were performed by specialists. Findings: Our patient felt palpitations and chest distress after intravenous Doxophylline. The electrocardiogram showed paroxysmal supraventricular tachycardia. There was no evidence to prove that there was any problem with his heart, liver, and kidney. According to the Naranjo Adverse Drug Reaction probability scale, paroxysmal supraventricular tachycardia has a probable relationship with Doxophylline. Implications: The paroxysmal supraventricular tachycardia is a rare but reasonable adverse reaction of Doxophylline, which should be paid more attention.

3.
Diabetol Metab Syndr ; 16(1): 206, 2024 Aug 24.
Artículo en Inglés | MEDLINE | ID: mdl-39182129

RESUMEN

OBJECTIVE: Type 2 diabetes mellitus (T2DM) has beenis known as an important risk factor for cognitive impairment. Meanwhile, the liver plays a central role in the development of T2DM and insulin resistance. The present study attempted to identify and validate marker genes for mild cognitive impairment (MCI) in patients with T2DM. METHODS: In this study, insulin resistance-related differentially expressed genes were identified from the liver tissues of individuals with T2DM and those with normal glucose tolerance using the Gene Expression Omnibus database and MCI-associated genes were identified using the GeneCards database. Next, enrichment analysis was performed with overlapping T2DM and MCI genes, followed by the identification of specific genes using the LASSO logistic regression and SVM-RFE algorithms. An important experiment involved the implementation of clinical and in vitro validation using real-time quantitative polymerase chain reaction (RT-qPCR). Finally, multiple linear regression, binary logistic regression, and receiver operating characteristic curve analyses were performed to investigate the relationship between the key gene and cognitive function in these patients. RESULT: The present study identified 40 overlapping genes between MCI and T2DM, with subsequent enrichment analysis revealing their significant association with the roles of neuronal and glial projections. The marker gene complement receptor 1(CR1) was identified for both diseases using two regression algorithms. Based on RT-qPCR validation in 65 T2DM patients with MCI (MCI group) and 65 T2DM patients without MCI (NC group), a significant upregulation of CR1 mRNA in peripheral blood mononuclear cells was observed in the MCI group (P < 0.001). Furthermore, the CR1 gene level was significantly negatively associated with MoCA and MMSE scores, which reflect the overall cognitive function, and positively correlated with TMTB scores, which indicate the executive function. Finally, elevated CR1 mRNA levels were identified as an independent risk factor for MCI (OR = 1.481, P < 0.001). CONCLUSION: These findings suggest that CR1 is an important predictor of MCI in patients with T2DM. Thus, CR1 has potential clinical significance, which may offer new ideas and directions for the management and treatment of T2DM. The identification and clinical validation of dysregulated marker genes in both T2DM and MCI can offer valuable insights into the intrinsic association between these two conditions. The current study insights may inspire the development of novel strategies for addressing the complicated issues related to cognitive impairment associated with diabetes.

4.
Cancer Med ; 13(15): e70037, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39109683

RESUMEN

BACKGROUND: Gastric cancer (GC), particularly for advanced stage of GC, commonly undergoes peritoneal metastasis (PM), which is the leading cause of GC-related death. However, there currently has no reliable biomarker to predict the onset of GCPM. It is well known that the imbalance of gut microbiota contributes to the development and metastasis of gastrointestinal tumors. Unfortunately, little is known about how the alternation in gut microbiota is associated with the onset of GCPM. METHODS: Our current study analyzed structural characteristics and functional prediction of gut microbiota in GC patients with PM (PM group) and without PM (non-PM group). Fresh fecal samples were collected from a discovery cohort (PM = 38, non-PM = 54) and a validation cohort (PM = 15, non-PM = 21) of GC patients and their 16S ribosomal RNA (16s rRNA) gene amplicons were sequenced, followed by bioinformatics. RESULTS: The results indicated an increase in the biodiversity of gut microbiota in the non-PM group of the discovery cohort, compared with the PM group. Moreover, LEfSe analysis found 31 significantly different microorganisms, of which the Roseburia ranked the fifth in the random forest (RF) model. The characteristics of intestinal microbiota in GCPM patients were changed, and the abundance of Roseburia in gut microbiota from the GCPM patients was reduced and receiver operating characteristic (ROC) analysis revealed that the reduced abundance of gut Roseburia effectively predicted the onset of GCPM. CONCLUSION: This signature was also observed in the validation cohort. Therefore, Roseburia is a protective microbial marker and the reduced abundance of Roseburia in gut microbiota may help early diagnosis of GCPM.


Asunto(s)
Heces , Microbioma Gastrointestinal , Neoplasias Peritoneales , ARN Ribosómico 16S , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patología , Neoplasias Gástricas/microbiología , Neoplasias Peritoneales/secundario , Neoplasias Peritoneales/microbiología , Masculino , Femenino , Persona de Mediana Edad , ARN Ribosómico 16S/genética , Heces/microbiología , Biomarcadores de Tumor/genética , Anciano , Clostridiales/aislamiento & purificación , Clostridiales/genética
5.
EBioMedicine ; 107: 105281, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39142074

RESUMEN

BACKGROUND: Coronavirus disease 2019 (COVID-19) is an immune-related disorder caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The complete pathogenesis of the virus remains to be determined. Unraveling the molecular mechanisms governing SARS-CoV-2 interactions with host cells is crucial for the formulation of effective prophylactic measures and the advancement of COVID-19 therapeutics. METHODS: We analyzed human lung single-cell RNA sequencing dataset to discern the association of butyrophilin subfamily 3 member A2 (BTN3A2) expression with COVID-19. The BTN3A2 gene edited cell lines and transgenic mice were infected by live SARS-CoV-2 in a biosafety level 3 (BSL-3) laboratory. Immunoprecipitation, flow cytometry, biolayer interferometry and competition ELISA assays were performed in BTN3A2 gene edited cells. We performed quantitative real-time PCR, histological and/or immunohistochemical analyses for tissue samples from mice with or without SARS-CoV-2 infection. FINDINGS: The BTN3A2 mRNA level was correlated with COVID-19 severity. BTN3A2 expression was predominantly identified in epithelial cells, elevated in pathological epithelial cells from COVID-19 patients and co-occurred with ACE2 expression in the same lung cell subtypes. BTN3A2 targeted the early stage of the viral life cycle by inhibiting SARS-CoV-2 attachment through interactions with the receptor-binding domain (RBD) of the Spike protein and ACE2. BTN3A2 inhibited ACE2-mediated SARS-CoV-2 infection by reducing ACE2 in vitro and in vivo. INTERPRETATION: These results reveal a key role of BTN3A2 in the fight against COVID-19. Identifying potential monoclonal antibodies which mimic BTN3A2 may facilitate disruption of SARS-CoV-2 infection, providing a therapeutic avenue for COVID-19. FUNDING: This study was supported by the National Natural Science Foundation of China (32070569, U1902215, and 32371017), the CAS "Light of West China" Program, and Yunnan Province (202305AH340006).


Asunto(s)
Enzima Convertidora de Angiotensina 2 , COVID-19 , Ratones Transgénicos , SARS-CoV-2 , Enzima Convertidora de Angiotensina 2/metabolismo , Enzima Convertidora de Angiotensina 2/genética , Animales , COVID-19/metabolismo , Humanos , SARS-CoV-2/fisiología , Ratones , Pulmón/virología , Pulmón/metabolismo , Pulmón/patología , Unión Proteica , Glicoproteína de la Espiga del Coronavirus/metabolismo , Glicoproteína de la Espiga del Coronavirus/genética , Femenino , Modelos Animales de Enfermedad , Masculino
6.
Front Med (Lausanne) ; 11: 1443133, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39144658

RESUMEN

Objective: This study aimed to investigate the role of galectin-3 (Gal-3; coded by LGALS3 gene), as a biomarker for MCI in T2DM patients and to develop and validate a predictive nomogram integrating galectin-3 with clinical risk factors for MCI prediction. Additionally, microRNA regulation of LGALS3 was explored. Methods: The study employed a cross-sectional design. A total of 329 hospitalized T2DM patients were recruited and randomly allocated into a training cohort (n = 231) and a validation cohort (n = 98) using 7:3 ratio. Demographic data and neuropsychological assessments were recorded for all participants. Plasma levels of galectin-3 were measured using ELISA assay. We employed Spearman's correlation and multivariable linear regression to analyze the relationship between galectin-3 levels and cognitive performance. Furthermore, univariate and multivariate logistic regression analyses were conducted to identify independent risk factors for MCI in T2DM patients. Based on these analyses, a predictive nomogram incorporating galectin-3 and clinical predictors was developed. The model's performance was evaluated in terms of discrimination, calibration, and clinical utility. Regulatory miRNAs were identified using bioinformatics and their interactions with LGALS3 were confirmed through qRT-PCR and luciferase reporter assays. Results: Galectin-3 was identified as an independent risk factor for MCI, with significant correlations to cognitive decline in T2DM patients. The developed nomogram, incorporating Gal-3, age, and education levels, demonstrated excellent predictive performance with an AUC of 0.813 in the training cohort and 0.775 in the validation cohort. The model outperformed the baseline galectin-3 model and showed a higher net benefit in clinical decision-making. Hsa-miR-128-3p was significantly downregulated in MCI patients, correlating with increased Gal-3 levels, while Luciferase assays confirmed miR-128-3p's specific binding and influence on LGALS3. Conclusion: Our findings emphasize the utility of Gal-3 as a viable biomarker for early detection of MCI in T2DM patients. The validated nomogram offers a practical tool for clinical decision-making, facilitating early interventions to potentially delay the progression of cognitive impairment. Additionally, further research on miRNA128's regulation of Gal-3 levels is essential to substantiate our results.

7.
Med ; 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-39025066

RESUMEN

BACKGROUND: ABO1020 is a monovalent COVID-19 mRNA vaccine. Results from a phase 1 trial showed ABO1020 was safe and well tolerated, and phase 3 trials to evaluate the efficacy, immunogenicity, and safety of ABO1020 in healthy adults are urgently needed. METHODS: We conducted a multinational, randomized, placebo-controlled, double-blind, phase 3 trial among healthy adults (ClinicalTrials.gov: NCT05636319). Participants were randomly assigned (1:1) to receive either 2 doses of ABO1020 (15 µg per dose) or placebo, administered 28 days apart. The primary endpoint was the vaccine efficacy in preventing symptomatic COVID-19 cases that occurred at least 14 days post-full vaccination. The second endpoint included the neutralizing antibody titers against Omicron BA.5 and XBB and safety assessments. FINDINGS: A total of 14,138 participants were randomly assigned to receive either vaccine or placebo (7,069 participants in each group). A total of 366 symptomatic COVID-19 cases were confirmed 14 days after the second dose among 93 participants in the ABO1020 group and 273 participants in the placebo group, yielding a vaccine efficacy of 66.18% (95% confidence interval: 57.21-73.27, p < 0.0001). A single dose or two doses of ABO1020 elicited potent neutralizing antibodies against both BA.5 and XBB.1.5. The safety profile of ABO1020 was characterized by transient, mild-to-moderate fever, pain at the injection site, and headache. CONCLUSION: ABO1020 was well tolerated and conferred 66.18% protection against symptomatic COVID-19 in adults. FUNDING: National Key Research and Development Project of China, Innovation Fund for Medical Sciences from the CAMS, National Natural Science Foundation of China.

8.
Clin Exp Med ; 24(1): 154, 2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-38972952

RESUMEN

Essential thrombocythemia (ET) and prefibrotic primary myelofibrosis (pre-PMF) are Philadelphia chromosome-negative myeloproliferative neoplasms. These conditions share overlapping clinical presentations; however, their prognoses differ significantly. Current morphological diagnostic methods lack reliability in subtype differentiation, underlining the need for improved diagnostics. The aim of this study was to investigate the multi-omics alterations in bone marrow biopsies of patients with ET and pre-PMF to improve our understanding of the nuanced diagnostic characteristics of both diseases. We performed proteomic analysis with 4D direct data-independent acquisition and microbiome analysis with 2bRAD-M sequencing technology to identify differential protein and microbe levels between untreated patients with ET and pre-PMF. Laboratory and multi-omics differences were observed between ET and pre-PMF, encompassing diverse pathways, such as lipid metabolism and immune response. The pre-PMF group showed an increased neutrophil-to-lymphocyte ratio and decreased high-density lipoprotein and cholesterol levels. Protein analysis revealed significantly higher CXCR2, CXCR4, and MX1 levels in pre-PMF, while APOC3, APOA4, FABP4, C5, and CFB levels were elevated in ET, with diagnostic accuracy indicated by AUC values ranging from 0.786 to 0.881. Microbiome assessment identified increased levels of Mycobacterium, Xanthobacter, and L1I39 in pre-PMF, whereas Sphingomonas, Brevibacillus, and Pseudomonas_E were significantly decreased, with AUCs for these genera ranging from 0.833 to 0.929. Our study provides preliminary insights into the proteomic and microbiome variations in the bone marrow of patients with ET and pre-PMF, identifying specific proteins and bacterial genera that warrant further investigation as potential diagnostic indicators. These observations contribute to our evolving understanding of the multi-omics variations and possible mechanisms underlying ET and pre-PMF.


Asunto(s)
Médula Ósea , Mielofibrosis Primaria , Proteómica , Trombocitemia Esencial , Femenino , Humanos , Masculino , Persona de Mediana Edad , Biopsia , Médula Ósea/patología , Médula Ósea/microbiología , Diagnóstico Diferencial , Microbiota , Multiómica , Mielofibrosis Primaria/patología , Trombocitemia Esencial/patología , Trombocitemia Esencial/diagnóstico , Trombocitemia Esencial/genética
9.
Acta Pharmacol Sin ; 2024 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-39075227

RESUMEN

A detailed chemical investigation of the Hainan soft coral Lobophytum crassum led to the identification of a class of polyoxygenated cembrane-type macrocyclic diterpenes (1-28), including three new flexible cembranoids, lobophycrasins E-G (2-4), and twenty-five known analogues. Their structures were elucidated by combining extensive spectroscopic data analysis, quantum mechanical-nuclear magnetic resonance (QM-NMR) methods, the modified Mosher's method, X-ray diffraction analysis, and comparison with data reported in the literature. Bioassays revealed that sixteen cembranoids inhibited the proliferation of H1975, MDA-MB231, A549, and H1299 cells. Among them, Compounds 10, 17, and 20 exhibited significant antiproliferative activities with IC50 values of 1.92-8.82 µM, which are very similar to that of the positive control doxorubicin. Molecular mechanistic studies showed that the antitumour activity of Compound 10 was closely related to regulation of the ROR1 and ErbB3 signalling pathways. This study may provide insight into the discovery and utilization of marine macrocyclic cembranoids as lead compounds for anticancer drugs.

10.
Zool Res ; 45(4): 877-909, 2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-39004865

RESUMEN

The tree shrew ( Tupaia belangeri) has long been proposed as a suitable alternative to non-human primates (NHPs) in biomedical and laboratory research due to its close evolutionary relationship with primates. In recent years, significant advances have facilitated tree shrew studies, including the determination of the tree shrew genome, genetic manipulation using spermatogonial stem cells, viral vector-mediated gene delivery, and mapping of the tree shrew brain atlas. However, the limited availability of tree shrews globally remains a substantial challenge in the field. Additionally, determining the key questions best answered using tree shrews constitutes another difficulty. Tree shrew models have historically been used to study hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, myopia, and psychosocial stress-induced depression, with more recent studies focusing on developing animal models for infectious and neurodegenerative diseases. Despite these efforts, the impact of tree shrew models has not yet matched that of rodent or NHP models in biomedical research. This review summarizes the prominent advancements in tree shrew research and reflects on the key biological questions addressed using this model. We emphasize that intensive dedication and robust international collaboration are essential for achieving breakthroughs in tree shrew studies. The use of tree shrews as a unique resource is expected to gain considerable attention with the application of advanced techniques and the development of viable animal models, meeting the increasing demands of life science and biomedical research.


Asunto(s)
Investigación Biomédica , Animales , Investigación Biomédica/tendencias , Tupaiidae , Modelos Animales de Enfermedad , Tupaia , Modelos Animales
11.
Genes (Basel) ; 15(7)2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-39062613

RESUMEN

Dendrobium loddigesii is a precious traditional Chinese medicine with high medicinal and ornamental value. However, the characterization of its mitochondrial genome is still pending. Here, we assembled the complete mitochondrial genome of D. loddigesii and discovered that its genome possessed a complex multi-chromosome structure. The mitogenome of D. loddigesii consisted of 17 circular subgenomes, ranging in size from 16,323 bp to 56,781 bp. The total length of the mitogenome was 513,356 bp, with a GC content of 43.41%. The mitogenome contained 70 genes, comprising 36 protein-coding genes (PCGs), 31 tRNA genes, and 3 rRNA genes. Furthermore, we detected 403 repeat sequences as well as identified 482 RNA-editing sites and 8154 codons across all PCGs. Following the sequence similarity analysis, 27 fragments exhibiting homology to both the mitogenome and chloroplast genome were discovered, accounting for 9.86% mitogenome of D. loddigesii. Synteny analysis revealed numerous sequence rearrangements in D. loddigesii and the mitogenomes of related species. Phylogenetic analysis strongly supported that D. loddigesii and D. Amplum formed a single clade with 100% bootstrap support. The outcomes will significantly augment the orchid mitochondrial genome database, offering profound insights into Dendrobium's intricate mitochondrial genome architecture.


Asunto(s)
Dendrobium , Especies en Peligro de Extinción , Genoma Mitocondrial , Filogenia , Dendrobium/genética , Dendrobium/clasificación , Genoma Mitocondrial/genética , China , ARN de Transferencia/genética , Secuenciación Completa del Genoma , Composición de Base , Cromosomas de las Plantas/genética , Genoma de Planta , Genoma del Cloroplasto
12.
Environ Pollut ; 356: 124332, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-38848963

RESUMEN

The bioremediation of chlorinated ethenes (CEs) contaminated groundwater is attracting increasingly attention in practical remediation projects. However, modelling of microbial metabolic processes under the constraints of substrate and environmental factors is inadequate. This study developed a new kinetic model, which incorporated the logistic model and Dual-Monod kinetic to represent the interaction between the controlled microbial growth and the bioavailable substrates in CE-contaminated groundwater. The proposed model was based on discrete observations to simulate microbial growth under the constraints of substrate and environmental conditions, reducing the amount of observational data required for the model. Meanwhile, the proposed model introduced two new kinetic parameters, the effective specific growth rate µeff and the real self-limiting coefficient of microbial growth keff,sl, to simplified the number of independent parameters. A parameter estimation method based on the quasi-Newton's algorithm for the proposed model was also developed. The model was validated based on the hypothetical data, experimental results, and a published dataset, demonstrated the successful simulation of microbial growth and the sequential biodegradation of PCE in groundwater systems (*E < 0.3). The monitoring duration and the sampling schedule have significant impacts on estimating the biological parameters, and large errors would be induced when the data from the periods of extremely low substrate concentration or microbial growth decline were involved in parameter estimation. The research suggested that the proposed kinetic model provided a new insight to express the limitation of microbial population growth due to the available substrates and environmental factors, and is hoping to be applied in actual CE-contaminated sites.


Asunto(s)
Biodegradación Ambiental , Biotransformación , Agua Subterránea , Contaminantes Químicos del Agua , Agua Subterránea/química , Agua Subterránea/microbiología , Contaminantes Químicos del Agua/metabolismo , Contaminantes Químicos del Agua/análisis , Cinética , Hidrocarburos Clorados/metabolismo
14.
Medicine (Baltimore) ; 103(26): e38540, 2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38941410

RESUMEN

RATIONALE: Thyroglossal duct carcinoma, a rare clinical condition characterized by ectopic thyroid adenocarcinoma within thyroglossal duct cysts (TGDCs), typically confirmed through intraoperative rapid pathology, this condition generally has a favorable prognosis. Nevertheless, comprehensive treatment guidelines across all disease stages are lacking, the purpose of this study is to report 1 case of the disease and propose the treatment plan for each stage of the disease. PATIENT CONCERNS: A patient presented with thyroid swelling, classified as C-TIRADS 4A following a physical examination. Preoperative thyroid puncture identified papillary thyroid carcinoma, and genetic testing revealed a BRAF gene exon 15-point mutation. Ancillary tests showed a slightly decreased thyroid stimulating hormone (TSH) level (0.172) with no other significant abnormalities. DIAGNOSES: Preoperative fine-needle aspiration cytology (FNAC) confirmed right-side thyroid cancer. Intraoperative exploration uncovered a TGDC and intraoperative rapid pathology confirmed thyroglossal duct carcinoma. INTERVENTIONS: A Sistrunk operation and ipsilateral thyroidectomy were performed. OUTCOMES: Postoperative recovery was satisfactory. LESSONS: Thyroglossal duct carcinoma is a rare disease affecting the neck. Due to limited clinical cases and the favorable prognosis associated with this condition, there is currently no established set of diagnostic and treatment guidelines. According to tumor size, lymph node metastasis, thyroid status and other factors, the corresponding treatment methods were established for each stage of thyroglossal duct cancer, which laid the foundation for the subsequent treatment development of this disease.


Asunto(s)
Quiste Tirogloso , Neoplasias de la Tiroides , Humanos , Quiste Tirogloso/cirugía , Quiste Tirogloso/patología , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/cirugía , Neoplasias de la Tiroides/diagnóstico , Neoplasias de la Tiroides/genética , Cáncer Papilar Tiroideo/patología , Cáncer Papilar Tiroideo/cirugía , Cáncer Papilar Tiroideo/diagnóstico , Cáncer Papilar Tiroideo/genética , Femenino , Tiroidectomía/métodos , Masculino , Proteínas Proto-Oncogénicas B-raf/genética , Adulto , Biopsia con Aguja Fina
15.
Breast Cancer Res ; 26(1): 105, 2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-38937788

RESUMEN

Circular RNAs (circRNAs) are a new group of endogenous RNAs recently found to be involved in the development of various diseases, including their confirmed involvement in the progression of several types of cancers. Unluckily, the abnormal expression and functions of circRNAs in breast cancer shall be further investigated. This work aims to elucidate the action and molecular mechanism of circHSDL2 in the malignant progression of breast cancer. Differential expression profiles of circRNAs in breast cancer tissues relative to normal breast tissues and in the exosomes of breast cancer patients compared to healthy women were analyzed from databases to identify potentially functional circRNAs. CircHSDL2 was selected for further investigation. Cell proliferation, migration and invasion assays were done to assess the effect of circHSDL2 overexpression on breast cancer cells. Bioinformatics test and dual-luciferase reporter experiments were done to explore the interaction between circHSDL2 and miRNA. Downstream target genes were further investigated through proteomics analysis and Western blotting. The influence of circHSDL2 on breast cancer in vivo was evaluated through xenograft experiments in nude mice. Functional analysis demonstrated circHSDL2 overexpression promoted the division, movement, and invasion of breast cancer cells both in vivo and in vitro. Mechanistically, circHSDL2 acted as a sponge for miR-7978 to affect ZNF704 expression and thereby regulate the Hippo pathway in breast cancer cells. In conclusion, circHSDL2 regulates the Hippo pathway through the miR-7978/ZNF704 axis to facilitate the malignancy of breast cancer. This may be a potential biomarker and treatment target.


Asunto(s)
Neoplasias de la Mama , Proliferación Celular , Progresión de la Enfermedad , Regulación Neoplásica de la Expresión Génica , Vía de Señalización Hippo , MicroARNs , Proteínas Serina-Treonina Quinasas , ARN Circular , Transducción de Señal , Animales , Femenino , Humanos , Ratones , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Neoplasias de la Mama/metabolismo , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Ratones Desnudos , MicroARNs/genética , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/metabolismo , ARN Circular/genética , Transducción de Señal/genética
16.
Cancer Biol Ther ; 25(1): 2338644, 2024 Dec 31.
Artículo en Inglés | MEDLINE | ID: mdl-38650446

RESUMEN

BACKGROUND: The prognosis for advanced intrahepatic cholangiocarcinoma (iCCA) is poor, and there remains an urgent need to develop efficient systemic therapy. The efficacy of Pembrolizumab immunotherapy combined with lenvatinibin in iCCA is still unclear. The role of Epstein-Barr-virus (EBV) as a biomarker in iCCA for response to immunotherapy needs further exploration. CASE PRESENTATION: We report a case of a 60-year-old female with EBV-associated advanced iCCA (EBVaiCCA) who progressed after first-line therapy. She accomplished an available response to the combination therapy of pembrolizumab with lenvatinib, with overall survival of 20 months. CONCLUSIONS: As far as we know, this is the first case report about the application of Pembrolizumab with lenvatinib for EBVaiCCA patients. This case indicates that the combination of immunotherapy and antiangiogenic therapy provides a glimmer of hope for advanced EBVaiCCA patients.


Asunto(s)
Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Colangiocarcinoma , Infecciones por Virus de Epstein-Barr , Compuestos de Fenilurea , Quinolinas , Humanos , Colangiocarcinoma/tratamiento farmacológico , Femenino , Quinolinas/uso terapéutico , Quinolinas/farmacología , Persona de Mediana Edad , Compuestos de Fenilurea/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/farmacología , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/tratamiento farmacológico , Infecciones por Virus de Epstein-Barr/virología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de los Conductos Biliares/tratamiento farmacológico , Neoplasias de los Conductos Biliares/virología , Neoplasias de los Conductos Biliares/patología , Herpesvirus Humano 4
17.
J Phys Chem Lett ; 15(14): 3843-3850, 2024 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-38557025

RESUMEN

The development of aqueous zinc ion batteries (AZIBs) is hindered by several problems, including Zn dendrite/corrosion, side reactions, and hydrogen evolution reaction (HER). Herein, trisodium citrate (NaCit) additive is introduced into the ZnSO4 electrolyte to guide the preferred Zn(002) crystal plane growth, while the Cit- is preferentially adsorbed on the active sites to suppress the HER and Zn corrosion, thus achieving uniform Zn deposition without dendrites. The stable cycle life can reach 2000 h at 0.25 mA cm-2/0.05 mAh cm-2. The density functional theory simulations further indicate that the parallely placed Cit- has the lowest adsorption energy (-6.617 eV); it can form a weak interaction with Zn metal to promote the growth of (002) crystal planes. Furthermore, the assembled Zn//polyaniline full cell and pouch cell both exhibit good rate performance and long cycling stability. The complexation and dissolubilization effects of the NaCit additive provide a means for designing high-performance AZIBs.

18.
Biol Direct ; 19(1): 19, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38429756

RESUMEN

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is the main subtype of esophageal cancer. Current therapeutic effect is far from satisfaction. Hence, identifying susceptible genes and potential targets is necessary for therapy of ESCC patients. METHODS: Plant homeodomain (PHD)-finger domain protein 5 A (PHF5A) expression in ESCC tissues was examined by immunohistochemistry. RNA interference was used for in vitro loss-of-function experiments. In vivo assay was performed using xenograft mice model by subcutaneous injection. Besides, microarray assay and co-immunoprecipitation experiments were used to study the potential downstream molecules of PHF5A in ESCC. The molecular mechanism between PHF5A and vascular endothelial growth factor A (VEGFA) was explored by a series of ubiquitination related assays. RESULTS: We found that PHF5A was highly expressed in ESCC tissues compared to normal tissues and that was correlated with poor prognosis of ESCC. Loss-of-function experiments revealed that PHF5A silence remarkably inhibited cell proliferation, migration, and induced apoptosis as well as cell cycle arrest. Consistently, in vivo assay demonstrated that PHF5A deficiency was able to attenuate tumor growth. Furthermore, molecular studies showed that PHF5A silencing promoted VEGFA ubiquitination by interacting with MDM2, thereby regulating VEGFA protein expression. Subsequently, in rescue experiments, our data suggested that ESCC cell viability and migration promoted by PHF5A were dependent on intact VEGFA. Finally, PI3K/AKT signaling rescue was able to alleviate shPHF5A-mediated cell apoptosis and cell cycle arrest. CONCLUSION: PHF5A is a tumor promoter in ESCC, which is dependent on VEGFA and PI3K/AKT signaling. PHF5A might serve as a potential therapeutic target for ESCC treatment.


Asunto(s)
Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Factor A de Crecimiento Endotelial Vascular , Animales , Humanos , Ratones , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago/genética , Carcinoma de Células Escamosas de Esófago/metabolismo , Carcinoma de Células Escamosas de Esófago/patología , Regulación Neoplásica de la Expresión Génica , Fosfatidilinositol 3-Quinasas/genética , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas de Unión al ARN/genética , Transactivadores/genética , Factor A de Crecimiento Endotelial Vascular/genética , Factor A de Crecimiento Endotelial Vascular/metabolismo
19.
Res Pract Thromb Haemost ; 8(1): 102318, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38433975

RESUMEN

Background: Acquired hemophilia A (AHA) is a rare hemorrhagic disorder caused by factor (F)VIII inhibitors. The diagnosis and management of AHA remains challenging because of its rarity and heterogeneity. Objectives: To analyze the characteristics of AHA to enhance our understanding of this disease and identify effective treatment strategies. To analyze the characteristics of AHA to enhance our understanding of this disease and identify effective treatment strategies. Methods: Clinical features of 165 patients with AHA from a single center between July 1997 and December 2021 were retrospectively analyzed. Results: The median age of patients at diagnosis was 45 years. The median time to diagnosis was 30 days. All 165 patients experienced bleeding, with a median bleeding score (BS) of 4 (range, 2-12). Hemostatic therapy was administered to 129 (78.2%) patients. Bleeding control was achieved in 80.0% of patients who received prothrombin complex concentrate and in 92.3% of patients who were treated with recombinant activated FVII. Of the 163 patients who received immunosuppressive therapy, 80 (49.1%) received rituximab-based therapy with a 93.3% complete remission (CR) rate, 50 (30.7%) received steroids plus cyclophosphamide with an 85.0% CR rate, and 22 (13.5%) received steroids alone with an 82.4% CR rate. Six cases relapsed after a median duration of 330 days. Immunosuppressive therapy-related adverse events were reported in 17 patients. Seven deaths were recorded. FVIII inhibitor titer of ≥15 BU/mL and BS of ≥6 were identified as significantly poor prognostic factors for CR. Conclusion: Immunosuppressive therapies yield remarkably high response rates, with a CR rate exceeding 80%; notably, the regimen containing rituximab exhibits a CR rate of approximately 90%. FVIII inhibitor titer of ≥5 BU/mL and BS of ≥6 were poor predictors of CR in patients with AHA.

20.
J Int Med Res ; 52(3): 3000605241233159, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38436278

RESUMEN

Neuronal intranuclear inclusion disease (NIID) is a rare progressive neurodegenerative disease that mainly manifests as dementia, muscle weakness, sensory disturbances, and autonomic nervous dysfunction. Herein, we report a 68-year-old Chinese woman who was hospitalized because of resting tremor and bradykinesia that had been present for 7 years. Five years prior, bradykinesia and hypermyotonia had become apparent. She had urinary incontinence and rapid eye movement sleep behavior disorder. She was diagnosed with Parkinson's disease (PD) and received levodopa and pramipexole, which relieved her motor symptoms. During hospitalization, diffusion-weighted imaging revealed a high-intensity signal along the cortical medullary junction. Moreover, a skin biopsy revealed the presence of intranuclear inclusions in adipocytes, fibroblasts, and sweat gland cells. NIID was diagnosed by testing the Notch 2 N-terminal-like C (NOTCH2NLC) gene. We report this case to remind doctors to consider NIID when diagnosing patients with symptoms indicative of Parkinson's disease. Moreover, we note that further research is needed on the mechanism by which levodopa is effective for NIID.


Asunto(s)
Enfermedades del Sistema Nervioso Autónomo , Enfermedades Neurodegenerativas , Enfermedad de Parkinson , Humanos , Femenino , Anciano , Enfermedades Neurodegenerativas/diagnóstico , Enfermedad de Parkinson/diagnóstico , Enfermedad de Parkinson/tratamiento farmacológico , Cuerpos de Inclusión Intranucleares , Levodopa/uso terapéutico , Hipocinesia , Errores Diagnósticos
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