Cell pyroptosis in picornavirus and its potential for treating viral infection

alexandrossfakianakis shared this article with you from Inoreader Cell pyroptosis in picornavirus and its potential for treating viral infection Via Journal of Medical Virology Abstract Cell pyroptosis has received increased attention due to the associations between innate immunity and disease, and it has become a major focal point recently due to in-depth studies of cancer. With increased research on pyroptosis, scientists have discovered that it has an essential role in viral infections, especially in the occurrence and development of some picornavirus infections. Many picornaviruses, including Coxsackievirus, a71 enterovirus, human rhinovirus, encephalomyocarditis virus, and foot-and-mouth disease virus induce pyroptosis to varying degrees. This review summarized the mechanisms by which these viruses induce cell pyroptosis, which can be an effective defense against pathogen infection. However, excessive inflammasome activation or pyroptosis also can damage the host's health or aggravate disease progression. Careful approaches that acknowledge this dual effect will aid in the exploration of picornavirus infections and the mechanisms that produce the inflammatory response. This information will promote the development of drugs that can inhibit cell pyroptosis and provide new avenues for future clinical treatment. This article is protected by copyright. All rights reserved. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Characterizing HIV-preventive, plasma tenofovir concentrations. A pooled participant-level data analysis from HIV pre-exposure prophylaxis (PrEP) clinical trials.

alexandrossfakianakis shared this article with you from Inoreader Characterizing HIV-preventive, plasma tenofovir concentrations. A pooled participant-level data analysis from HIV pre-exposure prophylaxis (PrEP) clinical trials. Via Clinical Infectious Diseases Advance Access Abstract Background Daily dosing of tenofovir disoproxil fumarate (TDF), with or without emtricitabine (FTC), has high efficacy in preventing HIV infection when individuals are adherent. The target protective plasma concentration of tenofovir (TFV), however, is not fully understood. The aim of this study is to estimate the protective TFV plasma concentration. Methods Participant data from TFV-based daily oral and topical active arms of phase III trials (iPrEx, VOICE and Partners PrEP) were pooled (n = 2,950). Individual specific risk scores (low and high risk) of acquiring HIV, based on an earlier placebo analysis, were created. Longitudinal TFV pharmacokinetics (PK), HIV outcome, individual risk scores and the effect of sex at birth data were integrated and analyzed using non-linear mixed effects models (NONMEM). Results Around 50% of the individuals were estimated to be adherent, which differed from self-reported adherenc e (∼90%) and large variation between longitudinal adherence patterns were identified. Following oral administration, the estimated protective TFV trough concentration was substantially higher in high risk females (45.8 ng/mL) compared to high risk males (16.1 ng/mL) and to low risk individuals (∼7.5 ng/mL). Dosing simulations indicated that high risk women require full adherence to maintain protective levels. Conclusions Using the largest PK-HIV outcome database to date, we developed a population adherence-PK-risk-outcome model. Our results indicate that high risk females need higher levels of plasma TFV to achieve HIV protection compared to males. HIV protection exceeds 90% in all populations if daily adherence is achieved. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Cytokine profile and cholesterol levels in patients with Niemann-Pick type C disease presenting neurological symptoms: The in vivo effect of miglustat and the in vitro effect of N-acetylcysteine and Coenzyme Q10

alexandrossfakianakis shared this article with you from Inoreader Cytokine profile and cholesterol levels in patients with Niemann-Pick type C disease presenting neurological symptoms: The <em>in vivo</em> effect of miglustat and the <em>in vitro</em> effect of N-acetylcysteine and Coenzyme Q10 Via ScienceDirect Publication: Experimental Cell Research Publication date: Available online 27 April 2022 Source: Experimental Cell Research Author(s): Tatiane G. Hammerschmidt, Bruna Donida, Jéssica L. Faverzani, Alana P. Moura, Bianca G. dos Reis, Andryele Z. Machado, Rejane G. Kessler, Fernanda M. Sebastião, Luiza S. Reinhardt, Dinara J. Moura, Carmen R. Vargas View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Factors Correlating with Survival Following Adjuvant or Definitive Radiosurgery for Large Brain Metastases

alexandrossfakianakis shared this article with you from Inoreader Factors Correlating with Survival Following Adjuvant or Definitive Radiosurgery for Large Brain Metastases Via Neuro-Oncology Advance Access Abstract Background We sought to identify variates correlating with overall survival (OS) in patients treated with surgery (S) plus adjuvant stereotactic radiosurgery (SRS) versus definitive SRS for large (>4cc) brain metastases (BrM). Methods We used univariate (UVA) and multivariate analyses (MVA) to identify survival correlates among eligible patients identified from a prospective registry and compared definitive SRS to S+ adjuvant SRS cohorts using propensity score-matched analysis (PSMA). Secondary outcomes were measured using the cumulative incidence (CI) method. Results We identified 364 patients; 127 and 237 were treated with S+SRS and definitive SRS, respectively. On UVA, SRS alone [HR1.73 (1.35,2.22) P<0.001), BrM quantity [HR 1.13 (1.06-1.22) (P<0.001)]; performance status (PS) [HR 2.78 (1.73-4.46) (P<0.001)]; extracranial disease (ECD) [HR 1.82 (1.37,2.40) (P<0.001)]; and receipt of systemic treatment after BrM therapy, [HR 0.58 (0.46-073) (P<0.001)] correlated with OS. On MVA, SRS alone [HR 1.81 (1.19,2.74) (P<0.0054)], SRS target volume [HR 1.03 (1.01,1.06) (P<0.0042)], and receipt of systemic treatment [HR 0.68 (0.50,0.93) (P<0.015)] correlated with OS. When PSMA was used to balance ECD, BrM quantity, PS, and SRS target volume, SRS alone remained correlated with worsened OS [HR 1.62 (1.20-2.19) (P=0.0015)]. CI of local failure requiring resection at 12 months was 3% versus 7% for S+SRS and SRS cohorts, respectively [(HR 2.04 (0.89-4.69) (P =0.091)]. CI of pachymeningeal failure at 12 months was 16% versus 0% for S+SRS and SRS. Conclusion SRS target volume, receipt of systemic therapies, and treatment with S+SRS instead of definitive SRS correlated with improved survival in patients with large BrM. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

The intrinsic and microenvironmental features of diffuse midline glioma; implications for the development of effective immunotherapeutic treatment strategies

alexandrossfakianakis shared this article with you from Inoreader The intrinsic and microenvironmental features of diffuse midline glioma; implications for the development of effective immunotherapeutic treatment strategies Via Neuro-Oncology Advance Access Abstract Diffuse midline glioma (DMG), including those of the brainstem (diffuse intrinsic pontine glioma), are pediatric tumors of the central nervous system (CNS). Recognized as the most lethal of all childhood cancers, palliative radiotherapy remains the only proven treatment option, however, even for those that respond, survival is only temporarily extended. DMG harbor an immunologically 'cold' tumor microenvironment (TME) with few infiltrating immune cells. The mechanisms underpinning the cold TME are not well understood. Low expression levels of immune checkpoint proteins, including PD-1, PD-L1 and CTLA-4, are recurring features of DMG and likely contribute to the lack of response to immune checkpoint inhibitors (ICIs). The unique epigenetic signatures (including stem cell-like methylation patterns), a low tumor mutational burden, and recurring somatic mutations (H3K27M, TP53, ACVR1, MYC and PIK3CA), possibly play a role in the reduced efficacy of traditional immunotherapies. Therefore, to circumvent the lack of efficacy thus far seen for the use of ICIs, adoptive cell transfer (including chimeric antigen receptor T cells) and the use of oncolytic viruses, are currently being evaluated for the treatment of DMG. It remains an absolute imperative that we improve our understanding of DMG's intrinsic and TME features if patients are to realize the potential benefits offered by these sophisticated treatments. Herein, we summarize the limitations of immunotherapeutic approaches, highlight the emerging safety and clinical efficacy shown for sophisticated cell-based therapies, as well as the evolving knowledge underpinning the DMG-immune axis, to guide in the development of immunotherapies that we hope will improve outcomes. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Tetrahedral framework nucleic acid carrying angiogenic peptide prevents bisphosphonate-related osteonecrosis of the jaw by promoting angiogenesis

alexandrossfakianakis shared this article with you from Inoreader Tetrahedral framework nucleic acid carrying angiogenic peptide prevents bisphosphonate-related osteonecrosis of the jaw by promoting angiogenesis Via International Journal of Oral Science - Issue International Journal of Oral Science, Published online: 27 April 2022; doi:10.1038/s41368-022-00171-7 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.