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1.
Gland Surg ; 13(6): 1108-1115, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-39015715

RESUMO

Background: Pituitary neuroendocrine tumors (PitNETs) are predominantly benign, though a minority may exhibit invasive tendencies. A diagnosis of metastatic PitNETs, in the absence of malignant histology, hinges on the identification of craniospinal and/or systemic metastases. Only a minority of PitNETs exhibit intracranial seeding. Notably, craniotomy for PitNETs excision is a prominent catalyst for iatrogenic seeding. Case Description: This article presented a compelling case that 15 years following craniotomy for the resection of a somatotroph PitNET, a lesion emerged at the left frontal base within the ethmoid sinus. Subsequent post-operative pathology unveiled a mature plurihormonal pituitary specific transcription factor 1 (PIT-1)-lineage PitNET. Growth hormone (GH) levels decreased significantly from 22.8 ng/mL pre-operation to 2 ng/mL post-operative, and concurrently, prolactin (PRL) levels decreased from 26.7 ng/mL pre-operation to 4.5 ng/mL post-operation. Furthermore, in the follow-up examination conducted 5 months after the operation, both GH and PRL levels were found to be within the normal range for the patient. This robustly suggested that the initial surgical procedure played a key role in the development of the lesion. Conclusions: This underscores the paramount significance of strictly adhering to the non-tumor removal during craniotomy for PitNETs excision. Regardless of apparent complete resection on imaging, it remains imperative to conduct routine follow-up evaluations, encompassing both imaging studies and hormone level assessments.

2.
FASEB J ; 38(1): e23394, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38149910

RESUMO

Neutrophils and their production of neutrophil extracellular traps (NETs) significantly contribute to neuroinflammation and brain damage after intracerebral hemorrhage (ICH). Although Akebia saponin D (ASD) demonstrates strong anti-inflammatory activities and blood-brain barrier permeability, its role in regulating NETs formation and neuroinflammation following ICH is uncharted. Our research focused on unraveling the influence of ASD on neuroinflammation mediated by NETs and the mechanisms involved. We found that increased levels of peripheral blood neutrophils post-ICH are correlated with worse prognostic outcomes. Through network pharmacology, we identified ASD as a promising therapeutic target for ICH. ASD administration significantly improved neurobehavioral performance and decreased NETs production in neutrophils. Furthermore, ASD was shown to upregulate the membrane protein NTSR1 and activate the cAMP signaling pathway, confirmed through transcriptome sequencing, western blot, and immunofluorescence. Interestingly, the NTSR1 inhibitor SR48692 significantly nullified ASD's anti-NETs effects and dampened cAMP pathway activation. Mechanistically, suppression of PKAc via H89 negated ASD's anti-NETs effects but did not affect NTSR1. Our study suggests that ASD may reduce NETs formation and neuroinflammation, potentially involving the NTSR1/PKAc/PAD4 pathway post-ICH, underlining the potential of ASD in mitigating neuroinflammation through its anti-NETs properties.


Assuntos
Hemorragia Cerebral , Armadilhas Extracelulares , Doenças Neuroinflamatórias , Saponinas , Farmacologia em Rede , Perfilação da Expressão Gênica , Saponinas/farmacologia , Armadilhas Extracelulares/efeitos dos fármacos , Doenças Neuroinflamatórias/tratamento farmacológico , Hemorragia Cerebral/tratamento farmacológico , Humanos , Animais , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Receptores de Neurotensina/metabolismo , Proteína-Arginina Desiminase do Tipo 4/metabolismo
3.
Front Neurol ; 14: 1179761, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37273702

RESUMO

Background: The World Health Organization (WHO) CNS5 classification system highlights the significance of molecular biomarkers in providing meaningful prognostic and therapeutic information for gliomas. However, predicting individual patient survival remains challenging due to the lack of integrated quantitative assessment tools. In this study, we aimed to design a WHO CNS5-related risk signature to predict the overall survival (OS) rate of glioma patients using machine learning algorithms. Methods: We extracted data from patients who underwent an operation for histopathologically confirmed glioma from our hospital database (2011-2022) and split them into a training and hold-out test set in a 7/3 ratio. We used biological markers related to WHO CNS5, clinical data (age, sex, and WHO grade), and prognosis follow-up information to identify prognostic factors and construct a predictive dynamic nomograph to predict the survival rate of glioma patients using 4 kinds machine learning algorithms (RF, SVM, XGB, and GLM). Results: A total of 198 patients with complete WHO5 molecular data and follow-up information were included in the study. The median OS time of all patients was 29.77 [95% confidence interval (CI): 21.19-38.34] months. Age, FGFR2, IDH1, CDK4, CDK6, KIT, and CDKN2A were considered vital indicators related to the prognosis and OS time of glioma. To better predict the prognosis of glioma patients, we constructed a WHO5-related risk signature and nomogram. The AUC values of the ROC curves of the nomogram for predicting the 1, 3, and 5-year OS were 0.849, 0.835, and 0.821 in training set, and, 0.844, 0.943, and 0.959 in validation set. The calibration plot confirmed the reliability of the nomogram, and the c-index was 0.742 in training set and 0.775 in validation set. Additionally, our nomogram showed a superior net benefit across a broader scale of threshold probabilities in decision curve analysis. Therefore, we selected it as the backend for the online survival prediction tool (Glioma Survival Calculator, https://who5pumch.shinyapps.io/DynNomapp/), which can calculate the survival probability for a specific time of the patients. Conclusion: An online prognosis predictor based on WHO5-related biomarkers was constructed. This therapeutically promising tool may increase the precision of forecast therapy outcomes and assess prognosis.

4.
Mater Horiz ; 9(5): 1479-1488, 2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35262131

RESUMO

Polarization-sensitive photodetectors are the core of optics applications and have been successfully demonstrated in photodetectors based on the newly-emerging metal-halide perovskites. However, achieving high polarization sensitivity is still extremely challenging. In addition, most of the previously reported photodetectors were concentrated on 1D lead-halide perovskites and 2D asymmetric intrinsic structure materials, but suffered from being external bias driven, lead-toxicity, poor stability and complex processes, severely limiting their practical applications. Here, we demonstrate a high-performance polarization-sensitive and stable polarization-sensitive UV photodetector based on a dendritic crystal lead-free metal-halide CsCu2I3/GaN heterostructure. By combining the anisotropic morphology and asymmetric intrinsic structure of CsCu2I3 dendrites with the isotropic material GaN film, a high specific surface area and built-in electric field are achieved, exhibiting an ultra-high polarization selectivity up to 28.7 and 102.8 under self-driving mode and -3 V bias, respectively. To our knowledge, such a high polarization selectivity has exceeded those of all of the reported perovskite-based devices, and is comparable to, or even superior to, those of the conventional 2D heterostructure materials. Interestingly, the unsealed device shows outstanding stability, and can be stored for over 2 months, and effectively maintained the performance even after repeated heating (373K)-cooling (300K) for different periods of time in ambient air, indicating a remarkable temperature tolerance and desired compatibility for applications under harsh conditions. Such excellent performance and simple method strongly show that the CsCu2I3/GaN heterojunction photodetector has great potential in practical applications with high polarization-sensitivity. This work provides a new insight into designing novel high-performance polarization-sensitive optoelectronic devices.

5.
Acta Histochem ; 124(4): 151879, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35358895

RESUMO

Formalin-fixed, paraffin-embedded (FFPE) tissues have been widely used in researches. Proteins and nucleic acids in prolonged FFPE tissues display different degrees of degradation. We investigated the effect of prolonged formalin fixation on protein expression in human brain tissues. Twenty-eight middle prefrontal front cortex tissue blocks from human brains prefixed in formalin were obtained from a brain bank. The tissue blocks were divided into two groups, the control group and the prolonged fixation group. Quantitative immunocytochemistry was used to analyse the biological markers of Fox-3, Rbfox3 (NeuN), glial fibrillary acidic protein (GFAP), ionized calcium binding adapter molecule-1 (IBA-1) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Nissl staining showed that positive signaling of Nissl body was significantly decreased by 16.6% in the prolonged fixation group. In addition, the staining intensity of Nissl body was negatively correlated with fixation time. The level of NeuN immunoreactivity (ir) was significantly reduced by 19.31% in the prolonged fixation group. Moreover, there was a significant negative correlation between NeuN-ir and fixation time. There were no significant changes in GFAP-ir, IBA-1-ir and GAPDH-ir between control group and the prolonged fixation group. Prolonged formalin-fixed tissues showed time- and molecule-dependent protein changes, which may be potential confounders in the clinic and researches. Our study suggested short formalin fixation time is recommended when using PPFE brain tissues.


Assuntos
Encéfalo , Formaldeído , Encéfalo/metabolismo , Humanos , Imuno-Histoquímica , Inclusão em Parafina , Fixação de Tecidos
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