Background: Tau hyper-phosphorylation has been considered a major contributor to neurodegeneration in Alzheimer's disease (AD) and related tauopathies, and has gained prominence in therapeutic development for AD. To elucidate the pathogenic mechanisms underlying AD and evaluate therapeutic approaches targeting tau, numerous transgenic mouse models that recapitulate critical AD-like pathology have been developed. Tau P301S transgenic mice is one of the most widely used mouse models in AD research. Extensive studies have demonstrated that sex significantly influences AD pathology, behavioral status, and therapeutic outcomes, suggesting that studies using mouse models of AD must consider sex-and age-related differences in neuropathology, behavior, and plasma content. Method: We systematically investigated differences in tau P301S transgenic mice (PS19 line) and wildtype littermates of different sex behavioral performance, tau neuropathology, and biomarkers in plasma and brain. Results: Male P301S transgenic mice exhibited significant changes in weight loss, survival rate, clasping, kyphosis, composite phenotype assessment, nest building performance, tau phosphorylation at Ser202/Thr205, and astrocyte activation compared to that of wild-type littermates. In contrast, female P301S transgenic mice were only sensitive in the Morris water maze and open field test. In addition, we characterized the absence of macrophage-inflammatory protein (MIP-3α) and the upregulation of interferon (IFN)-γ, interleukin (IL)-5, and IL-6 in the plasma of P301S transgenic mice, which can be served as potential plasma biomarkers in P301S Tg mice. Male P301S transgenic mice expressed more monokine induced by IFN-γ (MIG), tumor necrosis factor-α (TNF-α), IL-10, and IL-13 than those of female P301S mice. Conclusion: Our findings highlight sexual dimorphism in the behavior, neuropathology, and plasma proteins in tau P301S transgenic AD mice, indicating that the use of male P301S transgenic mice may be more suitable for assessing anti-phosphorylated tau therapeutic strategies for AD and related tauopathies, and the MIP-3α may be a new potential plasma biomarker.
Background: Anxiety and depression are common nonmotor symptoms of Parkinson's disease (PD). Objectives: We investigated whether Bisphenol A (BPA) is capable of inducing anxiety/depressive-like behaviors and neurotransmitter alterations that are similar to those observed in PD. Materials and Methods:To test this hypothesis, we used a zebrafish animal model and conducted behavioral and histological assays. Results: BPA produced anxiety/depression-like behavioral signs for 14 days following administration. Altered behavioral responses were accompanied by reductions of striatal dopamine transporter, and decrease in hippocampal 5-HT content. Conclusions: These results suggest that the nigrostriatal pathway might play a role in the etiology of anxiety/depression. Furthermore, dopamine transporter function, in particular, might play a critical role in the pathophysiology of anxiety/depression.
Tau hyper-phosphorylation has been considered a major contributor to neurodegeneration in Alzheimer’s disease (AD) and related tauopathies, and has gained prominence in therapeutic development for AD. To elucidate the pathogenic mechanisms underlying AD and evaluate therapeutic approaches targeting tau, numerous transgenic mouse models that recapitulate critical AD-like pathology have been developed. Tau P301S transgenic mice is one of the most widely used mouse models in AD research. Extensive studies have demonstrated that sex significantly influences AD pathology, behavioral status and therapeutic outcomes, suggesting that studies using mouse models of AD must consider sex- and age-related differences in neuropathology, behavior, and plasma content. Method: We systematically investigated differences in tau P301S transgenic mice (PS19 line) and wildtype littermates of different sex behavioral performance, tau neuropathology and biomarkers in plasma and brain. Results: Male P301S transgenic mice exhibited significant changes in weight loss, survival rate, clasping, kyphosis, composite phenotype assessment, nest building performance, tau phosphorylation at Ser202/Thr205 and astrocyte activation compared to that of wild type littermates. In contrast, female P301S transgenic mice were only sensitive in the Morris Water Maze and open field test. In addition, we characterized the upregulation of interferon (IFN)-γ, interleukin (IL)-5, and IL-6 and the absense of macrophage-inflammatory protein (MIP)-3α. Male P301S transgenic mice expressed more plasma biomarkers than those of female P301S mice. Conclusion: Our findings highlight sexual dimorphism in the behavior, neuropathology, and biomarkers in tau P301S transgenic AD mice, indicating that the use of male P301S transgenic mice may be more suitable for assessing anti-phosphorylated tau therapeutic strategies for AD and related tauopathies.
Mixed epithelial and stromal tumors of the kidney (MESTK) are rare and recently defined entities that comprise both epithelial and stromal cells. MESTK is mostly benign; however, to date, 18 borderline or malignant cases have been reported. In this study, we report a case of carcinosarcoma exhibiting a large carcinoma and small sarcoma component, and review the relevant literature. The patient was a 59-year-old woman who presented with a large mass in the left kidney having solid and focal cystic components. The patient underwent left radical nephrectomy. The tumor was gray-white and solid-cystic, with a relatively clear boundary. Microscopically, the tumor revealed benign and malignant components. The benign component consisted of multiple tubules, variable-sized cysts lined with benign epithelium, and hyalinized stroma. The malignant component was composed of predominantly small cell neuroendocrine carcinoma and a small quantity of adenocarcinoma, squamous cell carcinoma, and sarcoma. Finally, a diagnosis of the malignant MESTK was made. Certain cases of borderline or malignant transformation of MESTK have been published, so it is important to enhance findings made by other studies.
Background: Although spread through air spaces (STAS) is a robust biomarker in surgically resected lung cancer, its application to biopsies is challenging. Moreover, limited resection is not an effective treatment for STAS-positive lung adenocarcinoma. This study aimed to identify histologic features from preoperative percutaneous transthoracic needle biopsies (PTNBs) to predict STAS status in the subsequently resected specimens, and thus help in selecting the surgical extent.Methods: Between January 2014 and December 2015, 111 PTNB specimens and subsequent resection specimens from consecutive lung adenocarcinoma patients were retrospectively examined. Histopathologic features of PTNB specimens and presence of STAS in subsequent resection specimens were evaluated and correlations between them were analyzed statistically.Results: The study participants had a mean age of 59 years (range, 35–81) and included 50 men and 61 women. Thirty-six patients were positive for STAS whereas 75 were negative. The micropapillary/solid histologic subtypes of lung adenocarcinoma (26 of 39; 66.7%; P < 0.001), necrotic/tumor debris (31 of 42; 73.8%; P < 0.001), intratumoral budding (ITB) (20 of 33; 60.6%; P < 0.001), desmoplasia (35 of 41; 85.4%; P < 0.001), and grade 3 nuclei (12 of 14; 85.7%; P < 0.001) were more common in STAS-positive tumors. Micropapillary/solid histologic subtype (OR, 1.35; 95% CI: 1.06, 1.67), ITB (OR, 1.64; 95% CI: 1.09, 2.83), desmoplasia (OR, 1.83; 95% CI: 1.36, 3.12), and N stage (N1 stage: OR, 1.37; 95% CI: 1.19, 1.87) (N2 stage: OR, 1.29; 95% CI: 1.07, 1.73) were independent predictors of STAS. Conclusions: Micropapillary/solid histologic subtype, ITB, and desmoplasia in preoperative PTNB specimens were independently associated with STAS in the subsequent resection specimens. Therefore, these can predict STAS and may help to optimize therapeutic planning.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.