RESUMEN

BACKGROUND: Mammographic density has been associated with breast cancer risk, and is modulated by established breast cancer risk factors, such as reproductive and hormonal history, as well as lifestyle. Recent epidemiological and biological findings underscore the recognized benefits of breastfeeding in reducing breast cancer risk, especially for aggressive subtypes. Current research exploring the association among mammographic density, breastfeeding, and breast cancer is sparse. MAIN FINDINGS: Changes occur in the breasts during pregnancy in preparation for lactation, characterized by the proliferation of mammary gland tissues and the development of mammary alveoli. During lactation, the alveoli fill with milk, and subsequent weaning triggers the involution and remodeling of these tissues. Breastfeeding influences the breast microenvironment, potentially altering mammographic density. When breastfeeding is not initiated after birth, or is abruptly discontinued shortly after, the breast tissue undergoes forced and abrupt involution. Conversely, when breastfeeding is sustained over an extended period and concludes gradually, the breast tissue undergoes slow remodeling process known as gradual involution. Breast tissue undergoing abrupt involution displays denser stroma, altered collagen composition, heightened inflammation and proliferation, along with increased expression of estrogen receptor α (ERα) and progesterone receptor. Furthermore, elevated levels of pregnancy-associated plasma protein-A (PAPP-A) surpass those of its inhibitors during abrupt involution, enhancing insulin-like growth factor (IGF) signaling and collagen deposition. Prolactin and small molecules in breast milk may also modulate DNA methylation levels. Drawing insights from contemporary epidemiological and molecular biology studies, our review sheds light on how breastfeeding impacts mammographic density and explores its role in influencing breast cancer. CONCLUSION: This review highlights a clear protective link between breastfeeding and reduced breast cancer risk via changes in mammographic density. Future research should investigate the effects of breastfeeding on mammographic density and breast cancer risk among various ethnic groups and elucidate the molecular mechanisms underlying these associations. Such comprehensive research will enhance our understanding and facilitate the development of targeted breast cancer prevention and treatment strategies.

Asunto(s)

Densidad de la Mama , Lactancia Materna , Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/patología , Mamografía , Factores de Riesgo , Embarazo , Lactancia , Mama/diagnóstico por imagen , Mama/patología

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BACKGROUND: Acute lymphoblastic leukemia is the most common pediatric malignancy, characterized by fever, anemia, hemorrhage, and symptoms brought on by blasts infiltrating organs. CASE PRESENTATION: This is a case report of a 9-year-old Asian patient with acute lymphoblastic leukemia who presented with polyuria alone as a presenting feature without any other clinical manifestation; primary renal disease or inherited metabolic disease was highly suspected. However, the water deprivation test and water deprivation pressurization test suggested nephrogenic diabetes insipidus, and the renal biopsy displayed diffuse lymphocytic infiltration in the renal interstitium. Bone marrow aspiration was performed immediately, and a comprehensive diagnosis of B-lymphoblastic leukemia was finally made. CONCLUSIONS: Renal infiltration with leukemic blasts mostly remains asymptomatic, but our case suggests that it can present with nephrogenic diabetes insipidus. This case fully demonstrates that the presentation of extramedullary infiltration in acute lymphoblastic leukemia is varied. When the patient has renal diabetes insipidus as the first symptom, the possibility of hematological tumor infiltration should be considered when finding the cause, and timely bone marrow cytology should be performed.

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Diabetes Insípida Nefrogénica , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Niño , Diabetes Insípida Nefrogénica/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicaciones , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Masculino , Poliuria/etiología , Infiltración Leucémica/diagnóstico , Riñón/patología , Médula Ósea/patología

RESUMEN

The development of an efficient palladium probe holds significant application value, considering the detrimental impact of palladium contaminants on human health. Thus, it is critical to create a sensitive detection method. To this end, a fluorescent probe TM-TPA-Pd based on benzothianone structure was designed, using allyl carbonate as the Pd0 recognition unit. TM-TPA-Pd exhibited high sensitivity (1.4 eq), selectivity, near-infrared (NIR) fluorescence (798 nm), and low detection limit (0.46 µM) for Pd0 with a rapid "turn-on" fluorescence signal (5 min). Furthermore, TM-TPA-Pd has extremely low cytotoxicity and has been successfully applied to detecting cells and zebrafish, which has great potential for palladium detection in biological systems.

Asunto(s)

Colorantes Fluorescentes , Paladio , Pez Cebra , Animales , Colorantes Fluorescentes/química , Paladio/química , Paladio/análisis , Humanos , Espectrometría de Fluorescencia , Límite de Detección , Espectroscopía Infrarroja Corta/métodos

RESUMEN

The chicken embryo chorioallantoic membrane (CAM) model has played a crucial role in various aspects of cancer research. The purpose of this study is to help researchers clarify the research direction and prospects of the CAM model. A bibliometric analysis was conducted on the top 100 most cited articles on use of the CAM model in tumour research, retrieved from the Web of Science Core Collection database. Tools such as Bibliometrix, VOSviewer, CiteSpace and Excel were utilized for the visualization network analysis. The 100 articles analysed were mainly from the USA, China and European countries such as Germany and France. Tumour research involving CAM model experiments demonstrated reliability and scientific rigor (average citation count = 156.2). The analysis of keywords, topics and subject areas revealed that the applications of this model ranged from the biological characteristics of tumours to molecular mechanisms and signaling pathways, to recent developments in nanotechnology and clinical applications. Additionally, nude mouse experiments have been more frequently performed in recent years. We conclude that the CAM model is efficient, simple and cost-effective, and has irreplaceable value in various aspects of cancer research. In the future, the CAM model can further contribute to nanotechnology research.

Asunto(s)

Bibliometría , Membrana Corioalantoides , Neoplasias , Animales , Embrión de Pollo , Investigación Biomédica , Modelos Animales de Enfermedad

RESUMEN

BACKGROUND: Papillary thyroid cancer (PTC) with the BRAFV600E mutation is associated with a poorer prognosis. BRAF inhibitors may demonstrate limited efficacy due to emerging drug resistance. The Warburg effect may have cancer therapeutic implications. It is not known if the BRAFV600E mutation is associated with altered glucose metabolism in PTC. METHODS: This study examined the effect of the BRAFV600E and DRP1 on various cellular processes in PTC cells, including: cell proliferation, migration, invasion, mitochondrial fission, glucose metabolism, reactive oxygen species (ROS) generation and apoptosis. We used RT-qPCR to assess the expression of key glycolytic enzymes in thyroid cancer tissues. Additionally, the regulatory interaction between BRAFV600E and DRP1 was investigated through Western Blot and immunohistochemical staining. We further evaluated the impact of DRP1 in PTC and inhibitory effects of Dabrafenib and 2-DG in vitro and in vivo. RESULTS: We found that the BRAFV600E mutation significantly augments aerobic glycolysis while suppressing oxidative phosphorylation in PTC. We identified the BRAFV600E/p-ERK/p-DRP1(Ser616) signaling pathway as a critical mediator in PTC progression. The BRAFV600E/p-ERK/p-DRP1(Ser616) signaling pathway enhances cell proliferation by upregulating HK2 expression and thereby increasing aerobic glycolysis. Secondly, it inhibits apoptosis by promoting mitochondrial fission and reducing ROS levels. Moreover, we demonstrated that the combination therapy of 2-DG and Dabrafenib markedly impedes the progression of BRAFV600E-positive PTC. CONCLUSION: The BRAFV600E/p-ERK/p-DRP1(Ser616) signaling pathway plays a pivotal role in glucose metabolism reprogramming, contributing to the aggressiveness and progression of BRAFV600E-positive PTC. Our findings suggest that a combined therapeutic approach using 2-DG and Dabrafenib has potential to improve the outcome of PTC patients with BRAFV600E.

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Ageing is the most prominent risk for osteoarthritis (OA) development. This study aimed to investigate the role of phosphoinositide-specific phospholipase Cγ (PLCγ) 1, previously linked to OA progression, in regulating age-related changes in articular cartilage and subchondral bone. d-galactose (d-Gal) was employed to treat chondrocytes from rats and mice or injected intraperitoneally into C57BL/6 mice. RTCA, qPCR, Western blot and immunohistochemistry assays were used to evaluate cell proliferation, matrix synthesis, senescence genes and senescence-associated secretory phenotype, along with PLCγ1 expression. Subchondral bone morphology was assessed through micro-CT. In mice with chondrocyte-specific Plcg1 deficiency (Plcg1flox/flox; Col2a1-CreERT), articular cartilage and subchondral bone were examined over different survival periods. Our results showed that d-Gal induced chondrocyte senescence, expedited articular cartilage ageing and caused subchondral bone abnormalities. In d-Gal-induced chondrocytes, diminished PLCγ1 expression was observed, and its further inhibition by U73122 exacerbated chondrocyte senescence. Plcg1flox/flox; Col2a1-CreERT mice exhibited more pronounced age-related changes in articular cartilage and subchondral bone compared to Plcg1flox/flox mice. Therefore, not only does d-Gal induce senescence in chondrocytes and age-related changes in articular cartilage and subchondral bone, as well as diminished PLCγ1 expression, but PLCγ1 deficiency in chondrocytes may also accelerate age-related changes in articular cartilage and subchondral bone. PLCγ1 may be a promising therapeutic target for mitigating age-related changes in joint tissue.

Asunto(s)

Cartílago Articular , Condrocitos , Ratones Endogámicos C57BL , Fosfolipasa C gamma , Animales , Condrocitos/metabolismo , Fosfolipasa C gamma/metabolismo , Fosfolipasa C gamma/genética , Cartílago Articular/metabolismo , Cartílago Articular/patología , Ratones , Envejecimiento/metabolismo , Osteoartritis/patología , Osteoartritis/metabolismo , Osteoartritis/genética , Osteoartritis/etiología , Senescencia Celular , Ratas , Estrenos/farmacología , Galactosa/metabolismo , Proliferación Celular , Masculino , Huesos/metabolismo , Huesos/patología , Huesos/diagnóstico por imagen , Pirrolidinonas/farmacología

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The combination between macroscopic structure designs and microscopic material designs offers tremendous possibilities for the development of advanced electromagnetic wave (EMW) absorbers. Herein, we propose a metamaterial design to address persistent challenges in this field, including narrow bandwidth, low-frequency bottlenecks, and, particularly, the urgent issue of robustness (i.e., oblique, and polarized incidence). Our absorber features a semiconductive metal-organic framework/iron 2D/2D assembly (CuHT-FCIP) with abundant crystal/crystal heterojunctions and strong magneto-electric coupling networks. This design achieves remarkable EMW absorption across a broad range (2 to 40 GHz) at a thickness of just 9.3 mm. Notably, it maintains stable performance against oblique incidence (within 75°) and polarizations (both transverse electric and transverse magnetic). Furthermore, the absorber demonstrates high specific compressive strength (201.01 MPa·cm3·g-1) and low density (0.89 g·cm-3). This advancement holds promise for developing robust EMW absorbers with superior performance.

RESUMEN

Ensuring drug safety in the early stages of drug development is crucial to avoid costly failures in subsequent phases. However, the economic burden associated with detecting drug off-targets and potential side effects through in vitro safety screening and animal testing is substantial. Drug off-target interactions, along with the adverse drug reactions they induce, are significant factors affecting drug safety. To assess the liability of candidate drugs, we developed an artificial intelligence model for the precise prediction of compound off-target interactions, leveraging multi-task graph neural networks. The outcomes of off-target predictions can serve as representations for compounds, enabling the differentiation of drugs under various ATC codes and the classification of compound toxicity. Furthermore, the predicted off-target profiles are employed in adverse drug reaction (ADR) enrichment analysis, facilitating the inference of potential ADRs for a drug. Using the withdrawn drug Pergolide as an example, we elucidate the mechanisms underlying ADRs at the target level, contributing to the exploration of the potential clinical relevance of newly predicted off-target interactions. Overall, our work facilitates the early assessment of compound safety/toxicity based on off-target identification, deduces potential ADRs of drugs, and ultimately promotes the secure development of drugs.

RESUMEN

BACKGROUND: To investigate feasibility of utilizing enhanced neuromuscular blocking agents with selective recovery protocol during thyroid surgery with intraoperative neuromonitoring (IONM). METHODS: Two-hundred and ninety patients were randomized into two groups: group A 0.3 mg/kg rocuronium and group B 0.6 mg/kg. Sugammadex 2 mg/kg was injected if needed followed initial vagal stimulation (V0). Electromyography signals from vagus and recurrent laryngeal nerves before and after resection were recorded as V1, V2, R1, and R2. RESULTS: In group B, 30 patients (20.7%) had V0 signals <100 µV, compared to 9 (6.2%) in group A. After sugammadex administration, 144 patients (99.3%) in both groups achieved positive V1 signals. Group B demonstrated a shorter surgical time from rocuronium injection to V2 stimulation compared to group A, accompanied by a significantly lower incidence of intraoperative body movement (0 vs. 16 patients). CONCLUSIONS: 0.6 mg/kg rocuronium with selective use 2 mg/kg sugammadex for IONM in thyroid surgery can meet both anesthesia and surgery demands.

RESUMEN

Subcutaneous implantation is an unexpected complication of thyroid surgery. Our study aimed to analyze the clinical features and outcomes of implantation after thyroid surgery. We retrospectively searched for the patients with implants of thyroid tumor after surgery from our database prior to August 2023. The clinical and pathological data were reviewed. Six female patients with a mean age of 33.6 ± 13.3 years were enrolled in this study. There was a rare case with mucinous adenocarcinoma, three follicular thyroid carcinoma, and two papillary thyroid carcinoma. The case with primary enteric adenocarcinoma of thyroid with subcutaneous implantation was first reported. The patient with mucinous adenocarcinoma received six courses of TP regimen chemotherapy. Five cases received radioactive iodine therapy. After a mean of 69.5 months of follow-up, one case recurred in the lateral region, and no metastasis or recurrence happened in the other five cases. Although the implantation after thyroid surgery is uncommon, the cases serve as a reminder to take greater care to avoid implantation.

RESUMEN

Artificial intelligence transforms drug discovery, with phenotype-based approaches emerging as a promising alternative to target-based methods, overcoming limitations like lack of well-defined targets. While chemical-induced transcriptional profiles offer a comprehensive view of drug mechanisms, inherent noise often obscures the true signal, hindering their potential for meaningful insights. Here, we highlight the development of TranSiGen, a deep generative model employing self-supervised representation learning. TranSiGen analyzes basal cell gene expression and molecular structures to reconstruct chemical-induced transcriptional profiles with high accuracy. By capturing both cellular and compound information, TranSiGen-derived representations demonstrate efficacy in diverse downstream tasks like ligand-based virtual screening, drug response prediction, and phenotype-based drug repurposing. Notably, in vitro validation of TranSiGen's application in pancreatic cancer drug discovery highlights its potential for identifying effective compounds. We envisage that integrating TranSiGen into the drug discovery and mechanism research holds significant promise for advancing biomedicine.

Asunto(s)

Aprendizaje Profundo , Descubrimiento de Drogas , Fenotipo , Descubrimiento de Drogas/métodos , Humanos , Reposicionamiento de Medicamentos/métodos , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patología , Transcriptoma , Perfilación de la Expresión Génica/métodos , Antineoplásicos/farmacología , Inteligencia Artificial

RESUMEN

Background: Papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC) contribute to more than 95% of thyroid malignancies. However, synchronous PTC and FTC are less common; it is most commonly discovered incidentally as synchronous malignancies during operation, which adds difficulties to intraoperative decision-making and postoperative treatment. Therefore, we analyzed the clinicopathological characteristics and prognosis of patients with PTC and FTC in our center. Methods: We conducted a search of single PTC, single FTC, and synchronous PTC/FTC patients who received initial surgery treatment at Fudan University Shanghai Cancer Center from 2006 to 2018 and collected paraffin-embedded samples of synchronous patients. Clinicopathological characteristics were collected from the electronic medical record system. Follow-up was performed through telephone contact or medical records. Exome sequencing was performed by ThyroLead panel. Results: Total of 42 synchronous PTC/FTC patients, 244 single FTC patients, and 2,959 single PTC patients were included. It showed a similarity between the clinicopathological features of synchronous thyroid cancer patients and single PTC patients, with a greater proportion of females, higher probabilities of lymph node metastasis, and higher rate of concurrence of Hashimoto's disease. The disease-free survival (DFS) curve indicated a worse prognosis of the synchronous group and single PTC group compared to the single FTC group, who had a propensity for neck lymph node recurrence; however, logistic multivariate regression analysis did not find any factor related to recurrence in the synchronous group. After re-checking pathology, DNA extraction, and quality control, genetic alteration information of 62 samples including primary tumors and metastatic lymph nodes from 35 synchronous cancer patients was displayed. In total, 81 mutations and 1 fusion gene were identified, including mutations related to outcomes and targeted therapy. Besides, some rare mutations in thyroid cancer were found in these patients. Conclusions: To conclude, synchronous PTC/FTC tend to be incidentally discovered during or after operation, behaving more like single PTC. The prognosis of synchronous patients is worse than that of single FTC patients and supplemental cervical lymph node dissection, total thyroidectomy, and postoperative radioiodine therapy should be taken into consideration after diagnosis. The next-generation sequencing (NGS) showed a unique molecular feature of synchronous patients with some rare mutations.

RESUMEN

Kinase-targeted inhibitors hold promise for new therapeutic options, with multi-target inhibitors offering the potential for broader efficacy while minimizing polypharmacology risks. However, comprehensive experimental profiling of kinome-wide activity is expensive, and existing computational approaches often lack scalability or accuracy for understudied kinases. We introduce KinomeMETA, an artificial intelligence (AI)-powered web platform that significantly expands the predictive range with scalability for predicting the polypharmacological effects of small molecules across the kinome. By leveraging a novel meta-learning algorithm, KinomeMETA efficiently utilizes sparse activity data, enabling rapid generalization to new kinase tasks even with limited information. This significantly expands the repertoire of accurately predictable kinases to 661 wild-type and clinically-relevant mutant kinases, far exceeding existing methods. Additionally, KinomeMETA empowers users to customize models with their proprietary data for specific research needs. Case studies demonstrate its ability to discover new active compounds by quickly adapting to small dataset. Overall, KinomeMETA offers enhanced kinome virtual profiling capabilities and is positioned as a powerful tool for developing new kinase inhibitors and advancing kinase research. The KinomeMETA server is freely accessible without registration at https://kinomemeta.alphama.com.cn/.

Asunto(s)

Internet , Polifarmacología , Inhibidores de Proteínas Quinasas , Proteínas Quinasas , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/química , Proteínas Quinasas/metabolismo , Proteínas Quinasas/química , Proteínas Quinasas/genética , Humanos , Programas Informáticos , Algoritmos , Inteligencia Artificial , Descubrimiento de Drogas/métodos

RESUMEN

A rare case of an anomalous location of the orifice of the coronary artery was found in a 99-year-old male cadaver undergoing routine dissection. The presence of the right coronary artery (RCA), left coronary artery (LCA), and conus artery (conus branch) originating from the right Valsalva sinus are the characteristic findings of this case. Then, the LCA passed through the aorta and the pulmonary artery. The LCA and RCA branches were normal. These findings are useful for future surgical procedures, including cardiac catheterization.

Asunto(s)

Cadáver , Seno Aórtico , Anciano de 80 o más Años , Humanos , Masculino , Anomalías de los Vasos Coronarios , Vasos Coronarios/anatomía & histología , Pueblos del Este de Asia , Japón , Seno Aórtico/anomalías , Seno Aórtico/diagnóstico por imagen

RESUMEN

BACKGROUND: Cervical sagittal alignment is crucial for distributing the head load to lower cervical segments and maintaining normal cervical spine function, but its biomechanical effect on the cervical spine was not fully elucidated. OBJECTIVE: To investigate the effect of cervical sagittal alignment on dynamic intervertebral kinematics. DESIGN: Cross-sectional study. METHODS: Healthy participants without neck pain were recruited and divided into lordosis, straight and kyphosis groups according to the C2-C7 Cobb angle at the neutral position. The anti-directional and total joint motions were extracted across 10 epochs of dynamic cervical flexion and extension movements. RESULTS: /findings: The overall anti-directional joint motion during flexion is larger in the kyphosis group when compared with the lordosis group (p = 0.021), while the range of flexion is smaller in the kyphosis group than that in the lordosis group (p = 0.017). The C2/C3 anti-directional joint motion during extension in the straight group is larger than that in the lordosis group (p = 0016). The range of extension in the kyphosis group (p < 0.001) and the straight group (p = 0.002) are larger than that in the lordosis group. The increased range of extension in the kyphosis and straight groups were mainly from the C3/C4, C4/C5, and C5/C6 joints(p < 0.05). CONCLUSION: Changes in cervical sagittal alignment alter both the quality and quantity of the individual joint motions. More adjustments are required by the cervical joints to complete neck movements with the loss of lordosis. The lordotic curvature is a relatively effort-saving mode for the cervical spine from a biomechanical perspective.

Asunto(s)

Vértebras Cervicales , Cifosis , Lordosis , Rango del Movimiento Articular , Humanos , Vértebras Cervicales/fisiopatología , Vértebras Cervicales/diagnóstico por imagen , Masculino , Estudios Transversales , Femenino , Fenómenos Biomecánicos , Adulto , Lordosis/fisiopatología , Lordosis/diagnóstico por imagen , Rango del Movimiento Articular/fisiología , Cifosis/fisiopatología , Cifosis/diagnóstico por imagen , Fluoroscopía/métodos , Voluntarios Sanos , Adulto Joven

RESUMEN

Although papillary thyroid cancer (PTC) has a good prognosis, its recurrence rate is high and remains a core concern in the clinic. Molecular factors contributing to different recurrence risks (RRs) remain poorly defined. Here, we perform an integrative proteogenomic and metabolomic characterization of 102 Chinese PTC patients with different RRs. Genomic profiling reveals that mutations in MUC16 and TERT promoter as well as multiple gene fusions like NCOA4-RET are enriched by the high RR. Integrative multi-omics analyses further describe the multi-dimensional characteristics of PTC, especially in metabolism pathways, and delineate dominated molecular patterns of different RRs. Moreover, the PTC patients are clustered into four subtypes (CS1: low RR and BRAF-like; CS2: high RR and metabolism type, worst prognosis; CS3: high RR and immune type, better prognosis; CS4: high RR and BRAF-like) based on the omics data. Notably, the subtypes display significant differences considering BRAF and TERT promoter mutations, metabolism and immune pathway profiles, epithelial cell compositions, and various clinical factors (especially RRs and prognosis) as well as druggable targets. This study can provide insights into the complex molecular characteristics of PTC recurrences and help promote early diagnosis and precision treatment of recurrent PTC.

Asunto(s)

Proteogenómica , Neoplasias de la Tiroides , Humanos , Cáncer Papilar Tiroideo/genética , Proteínas Proto-Oncogénicas B-raf/genética , Metabolómica , Neoplasias de la Tiroides/genética

RESUMEN

Both anaplastic thyroid cancer (ATC) and papillary thyroid cancer (PTC) originate from thyroid follicular epithelial cells, but ATC has a significantly worse prognosis and shows resistance to conventional therapies. However, clinical trials found that immunotherapy works better in ATC than late-stage PTC. Here, we used single-cell RNA sequencing (scRNA-Seq) to generate a single-cell atlas of thyroid cancer. Differences in ATC and PTC tumor microenvironment components (including malignant cells, stromal cells, and immune cells) leading to the polarized prognoses were identified. Intriguingly, we found that CXCL13+ T lymphocytes were enriched in ATC samples and might promote the development of early tertiary lymphoid structure (TLS). Last, murine experiments and scRNA-Seq analysis of a treated patient's tumor demonstrated that famitinib plus anti-PD-1 antibody could advance TLS in thyroid cancer. We displayed the cellular landscape of ATC and PTC, finding that CXCL13+ T cells and early TLS might make ATC more sensitive to immunotherapy.

Asunto(s)

Quimiocina CXCL13 , Inmunoterapia , Cáncer Papilar Tiroideo , Carcinoma Anaplásico de Tiroides , Neoplasias de la Tiroides , Microambiente Tumoral , Microambiente Tumoral/inmunología , Humanos , Carcinoma Anaplásico de Tiroides/patología , Carcinoma Anaplásico de Tiroides/terapia , Carcinoma Anaplásico de Tiroides/inmunología , Animales , Ratones , Cáncer Papilar Tiroideo/patología , Cáncer Papilar Tiroideo/inmunología , Cáncer Papilar Tiroideo/genética , Cáncer Papilar Tiroideo/terapia , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/inmunología , Neoplasias de la Tiroides/terapia , Neoplasias de la Tiroides/genética , Inmunoterapia/métodos , Quimiocina CXCL13/metabolismo , Quimiocina CXCL13/genética , Estructuras Linfoides Terciarias/inmunología , Estructuras Linfoides Terciarias/patología , Análisis de la Célula Individual , Pronóstico , Linfocitos T/inmunología , Femenino , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/farmacología , Masculino

RESUMEN

Senescent kidney can lead to the maladaptive repairment and predispose age-related kidney diseases. Here, we explore the renal anti-senescence effect of a known kind of drug, sodium-dependent glucose transporters 2 inhibitor (SGLT2i). After 4 months intragastrically administration with dapagliflozin on senescence-accelerated mouse prone 8 (SAMP8) strain mice, the physiologically effects (lowering urine protein, enhancing glomerular blood perfusion, inhibiting expression of senescence-related biomarkers) and structural changes (improving kidney atrophy, alleviating fibrosis, decreasing glomerular mesangial proliferation) indicate the potential value of delaying kidney senescence of SGLT2i. Senescent human proximal tubular epithelial (HK-2) cells induced by H2 O2 also exhibit lower senescent markers after dapagliflozin treatment. Further mechanism exploration suggests LTBP2 have the great possibility to be the target for SGLT2i to exert its renal anti-senescence role. Dapagliflozin down-regulate the LTBP2 expression in kidney tissues and HK-2 cells with senescent phenotypes. Immunofluorescence staining show SGLT2 and LTBP2 exist colocalization, and protein-docking analysis implies there is salt-bridge formation between them; these all indicate the possibility of weak-interaction between the two proteins. Apart from reducing LTBP2 expression in intracellular area induced by H2 O2 , dapagliflozin also decrease the concentration of LTBP2 in cell culture medium. Together, these results reveal dapagliflozin can delay natural kidney senescence in non-diabetes environment; the mechanism may be through regulating the role of LTBP2.

Asunto(s)

Enfermedades Renales , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Ratones , Humanos , Animales , Inhibidores del Cotransportador de Sodio-Glucosa 2/farmacología , Riñón/metabolismo , Glucósidos/uso terapéutico , Compuestos de Bencidrilo/farmacología , Compuestos de Bencidrilo/uso terapéutico , Enfermedades Renales/metabolismo , Proteínas de Unión a TGF-beta Latente

RESUMEN

Objective: At present, the structure of knowledge in the field of childhood thyroid cancer is not clear enough, and scholars lack a sufficient understanding of the developing trends in this field, which has led to a shortage of forward-looking outputs. The purpose of this research is to help scholars construct a complete knowledge framework and identify current challenges, opportunities, and development trends. Methods: We searched the literature in the Web of Science Core Collection database on August 7, 2023 and extracted key information from the top 100 most cited articles, such as the countries, institutions, authors, themes, and keywords. We used bibliometric tools such as bibliometrix, VOSviewer, and CiteSpace for a visualization analysis and Excel for statistical descriptions. Results: The top 100 most cited articles fluctuated over time, and the research was concentrated in European countries, the United States, and Japan, among which scientific research institutions and scholars from the United States made outstanding contributions. Keyword analysis revealed that research has shifted from simple treatment methods for pediatric thyroid cancer (total thyroidectomy) and inducing factors (the Chernobyl power station accident) to the clinical applications of genetic mutations (such as the BRAF and RET genes) and larger-scale genetic changes (mutation studies of the DICER1 gene). The thematic strategy analysis showed an increasing trend towards the popularity of fusion oncogenes, while the popularity of research on traditional treatments and diagnostics has gradually declined. Conclusion: Extensive research has been conducted on the basic problems of pediatric thyroid cancer, and there has been significant outputs in the follow-up and cohort analysis of conventional diagnostic and treatment methods. However, these methods still have certain limitations. Therefore, scholars should focus on exploring fusion genes, the clinical applications of molecular targets, and novel treatment methods. This study provides a strong reference for scholars in this field.

RESUMEN

This study investigated the soil physicochemical properties and vegetation community characteristics of the Baotou light rare earth tailings pond after 10 years of aggregate spray seeding ecological restoration (S1) and ordinary soil spray seeding ecological restoration (S2), and the naturally restored dam slope area without human intervention (S3). The results showed that the vegetation community of S1 was dominated by Caragana korshinskii Kom, and its importance and abundance values were 0.40 and 38.4, respectively, while the vegetation communities of S2 and S3 mainly comprised herbaceous plants. Additionally, the vegetation biomass of S1 was significantly higher than that of S2 and S3 by 215.20% and 1345.76%, respectively, and the vegetation diversity index of S1 was the highest among the three treatment groups. The soil porosity (SP), water content (W), electrical conductivity (EC), and available K were significantly improved in S1, while soil bulk density (BD) was significantly reduced compared with that of S2 and S3. In addition, redundancy analysis revealed that SP, EC, W, and K positively correlate with the biomass, Shannon, Pielou, Simpson, and Marglef indices. Principal component analysis further showed that the comprehensive score of S1 (0.983) was higher than that of S2 (- 0.261) and S3 (- 0.648). Collectively, these findings indicate that appropriate ecological restoration can improve soil structure and vegetation community characteristics, thereby accelerating vegetation restoration, ultimately increasing the stability of the ecosystem.

Asunto(s)

Ecosistema , Metales de Tierras Raras , Humanos , Suelo/química , Estanques , Plantas , China