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The cellular prion protein (PrPC) plays many roles in the developing and adult brain. In addition, PrPC binds to several amyloids in oligomeric and prefibrillar forms and may act as a putative receptor of abnormal misfolded protein species. The role of PrPC in tau seeding and spreading is not known. In the present study, we have inoculated well-characterized sarkosyl-insoluble fractions of sporadic Alzheimer's disease (sAD) into the brain of adult wild-type mice (Prnp+/+), Prnp0/0 (ZH3 strain) mice, and mice over-expressing the secreted form of PrPC lacking their GPI anchor (Tg44 strain). Phospho-tau (ptau) seeding and spreading involving neurons and oligodendrocytes were observed three and six months after inoculation. 3Rtau and 4Rtau deposits from the host tau, as revealed by inoculating Mapt0/0 mice and by using specific anti-mouse and anti-human tau antibodies suggest modulation of exon 10 splicing of the host mouse Mapt gene elicited by exogenous sAD-tau. However, no tau seeding and spreading differences were observed among Prnp genotypes. Our results show that PrPC does not affect tau seeding and spreading in vivo. [ABSTRACT FROM AUTHOR]

Abstract The cellular prion protein (PrPC) plays many roles in the developing and adult brain. In addition, PrPC binds to several amyloids in oligomeric and prefibrillar forms and may act as a putative receptor of abnormal misfolded protein species. The role of PrPC in tau seeding and spreading is not known. In the present study, we have inoculated well-characterized sarkosyl-insoluble fractions of sporadic Alzheimer’s disease (sAD) into the brain of adult wild-type mice (Prnp +/+), Prnp 0/0 (ZH3 strain) mice, and mice over-expressing the secreted form of PrPC lacking their GPI anchor (Tg44 strain). Phospho-tau (ptau) seeding and spreading involving neurons and oligodendrocytes were observed three and six months after inoculation. 3Rtau and 4Rtau deposits from the host tau, as revealed by inoculating Mapt 0/0 mice and by using specific anti-mouse and anti-human tau antibodies suggest modulation of exon 10 splicing of the host mouse Mapt gene elicited by exogenous sAD-tau. However, no tau seeding and spreading differences were observed among Prnp genotypes. Our results show that PrPC does not affect tau seeding and spreading in vivo.

Introduction: One of the many reasons for cancer treatment failure and recurrence is acquired Multidrug Resistance (MDR). Overcoming cancer drug resistance has been the focus of researchers' studies. Cellular prion protein (PrPC) is a glycophosphatidylinositol-anchored cell-surface glycoprotein that has been implicated in tumor behavior, including proliferation, apoptosis, invasion, metastasis, and chemoresistance. >Method: Lupiwighteone (Lup), a natural isoflavone found in the root of Glycyrrhiza glabra, has anticancer activity against prostate cancer cells, neuroblastoma cells, and human breast cancer cells. However, its pharmacological effects and mechanisms in drug-resistant cancer cells have not been reported. In this study, we used an adriamycin- resistant leukemia K562 cell model, and for the first time, we investigated the reversal effect of Lup on its MDR and the potential mechanism., Result: The results indicated that Lup could induce apoptosis through the mitochondrial pathway while upregulating the expression of related apoptotic proteins, such as Bax, Cyto C, Caspase-3, and PARP1. Autophagy is commonly recognized as a protective mechanism that mediates MDR during treatment. We found that Lup induced cellular autophagy while upregulating the expression of related autophagy proteins such as Beclin 1 and LC3 II., Conclusion: In addition, when Lup was combined with adriamycin, Lup decreased the IC50 of K562/ADR cells; moreover, Lup can downregulate the expression of drug-resistant proteins, suggesting that Lup can reverse drug resistance. Further studies have shown that Lup can downregulate the expression of PrPC-PI3K-Akt axis proteins and PrPC-Oct4 axis proteins. This study demonstrated that Lup has the potential to inhibit the proliferation of K562/ADR cells by targeting PrPC, and further study of the signaling pathway associated with PrPC may provide the experimental basis for the treatment of drug-resistant leukemia., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Oral squamous cell carcinoma (OSCC) is frequently diagnosed at an advanced stage, and the high mortality of patients is mainly due to the delay of diagnosis. Cellular prion protein (PrP C ) contributes to the occurrence and development of many malignant tumors. However, little has been known about the clinical and diagnostic value of PrP C in OSCC. This study investigated the levels of PrP C in the saliva and serum of patients with OSCC, OPMD and control group and their diagnostic value. Methods: The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) and Clinical Proteome Tumor Analysis Consortium (CPTAC) databases were analyzed to evaluate the expression of human prion protein gene ( PRNP ) mRNA and PrP C in OSCC. Enzyme-linked Immunosorbent Assay (ELISA) was utilized to detect the expression of PrP C in saliva and serum samples of OSCC, OPMD and control groups. Furthermore, diagnostic value and clinical significance of PrP C in OSCC was identified. Protein-protein interaction (PPI) network was constructed by STRING. GO and KEGG analysis were performed by ClusterProfiler. Results: The levels of PRNP mRNA and PrP C in OSCC were significantly higher than those in the control group from databases ( P <0.05). Besides, salivary and serum PrP C of OSCC patients showed increased levels compared with OPMD and control groups ( P <0.05). The expression of salivary and serum PrP C of OSCC was correlated with the degree of differentiation ( P <0.05), and the expression of PrP C from CPTAC was related to tumor stage of OSCC ( P <0.05). The areas under the diagnostic curves (AUCs) of salivary and serum PrP C were 0.807 and 0.671, respectively. GO and KEGG analysis revealed that PrP C might be related to cell adhesion, cell differentiation, signal transduction and apoptosis, and participate in the pathways of focal adhesion, PI3K-Akt signaling pathway and ECM- receptor interaction in OSCC. Conclusion: PrP C in saliva and serum may be a potential biomarker for early diagnosis of OSCC., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: Twitter is a common platform for people to share opinions, discuss health-related topics, and engage in conversations with a wide audience. Twitter users frequently share health information related to chronic diseases, mental health, and general wellness topics. However, sharing health information on Twitter raises privacy concerns as it involves sharing personal and sensitive data on a web-based platform., Objective: This study aims to adopt an interactive approach and develop a model consisting of privacy concerns related to web-based vendors and web-based peers. The research model integrates the 4 dimensions of concern for information privacy that express concerns related to the practices of companies and the 4 dimensions of peer privacy concern that reflect concerns related to web-based interactions with peers. This study examined how this interaction may affect individuals' information-sharing behavior on Twitter., Methods: Data were collected from 329 Twitter users in the United States using a web-based survey., Results: Results suggest that privacy concerns related to company practices might not significantly influence the sharing of general health information, such as details about hospitals and medications. However, privacy concerns related to companies and third parties can negatively shape the disclosure of specific health information, such as personal medical issues (β=-.43; P<.001). Findings show that peer-related privacy concerns significantly predict sharing patterns associated with general (β=-.38; P<.001) and specific health information (β=-.72; P<.001). In addition, results suggest that people may disclose more general health information than specific health information owing to peer-related privacy concerns (t 165 =4.72; P<.001). The model explains 41% of the variance in general health information disclosure and 67% in specific health information sharing on Twitter., Conclusions: The results can contribute to privacy research and propose some practical implications. The findings provide insights for developers, policy makers, and health communication professionals about mitigating privacy concerns in web-based health information sharing. It particularly underlines the importance of addressing peer-related privacy concerns. The study underscores the need to build a secure and trustworthy web-based environment, emphasizing the significance of peer interactions and highlighting the need for improved regulations, clear data handling policies, and users' control over their own data., (©Pouyan Esmaeilzadeh. Originally published in JMIR Formative Research (https://formative.jmir.org), 12.01.2024.)