interferon (Shanferon)

A Biomimetic In Vitro Model of the Pro-Inflammatory Microenvironment Recapitulates Type I/II Interferon Signaling and Refractory Acute Monocytic Leukemia.

Krasnov Kirill K, Kobyakova Margarita M, Meshcheriakova Elena E, Lomovskaya Yana Y et al.

Preclinical drug development suffers from a persistent translational gap, as conventional animal models fail to reproduce the human immune response, contributing to high attrition rates of drug candidates in clinical trials. To address this, we previously established an in vitro high-density culture (HDC) model of acute monocytic leukemia (AML) cells that recapitulates an aseptic pro-inflammatory microenvironment using acute monocytic leukemia (AMoL) THP-1 cells. In the present study, using RNA-seq, quantitative RT-PCR, flow cytometry, Western blotting, and multiplex cytokine analysis, we characterized how this biomimetic microenvironment shapes Type I and II interferon signaling in THP-1 cells that acquire resistance to apoptosis under HDC conditions. The model revealed predominant activation of the Type II interferon pathway, marked by elevated interferon-gamma expression, STAT1 activation, and increased production of interferon-stimulated chemokines. Protein-protein interaction network analysis identified key interferon-induced hub genes and regulatory transcription factors driving this response. Notably, the interferon-stimulated gene profile generated by this in vitro platform, including the Interferon-Related DNA Damage Resistance Signature, closely resembled gene expression patterns observed in clinical samples from patients with refractory AMoL, supporting the relevance of the HDC biomimetic system as a research model of inflammatory adaptation in leukemia cells and associated resistance. These findings support further investigation of the HDC biomimetic system as a research model of inflammatory adaptation in leukemia cells and associated resistance.

Prevalence of Decisional Regret and Associated Risk Factors in Patients With Hepatitis B Undergoing Pegylated Interferon Alpha Therapy.

Lin Yufen Y, Xiong Huan H, Yi Shuanglian S, Xie Shanshan S

Pegylated interferon alpha has been shown to enhance the likelihood of achieving a functional cure in patients with hepatitis B. However, it was associated with a greater number of contraindications and adverse reactions compared with nucleotide analogs. Current research has placed comparatively less emphasis on the potential for this treatment to induce decision regret among patients. The aim of this study was to investigate the current status of decision regret in hepatitis B patients undergoing interferon therapy and to explore its influencing factors. A cross-sectional study was conducted in a comprehensive hospital in Xiamen, Fujian Province, China, from February 20 to June 13, 2024. The study recruited hepatitis B patients undergoing treatment with pegylated interferon alpha. The survey encompassed general information, the All Aspects of Health Literacy Scale, the Perceived Social Support Scale, the Control Preferences Scale, the Decisional Conflict Scale, and the Decision Regret Scale. A total of 130 questionnaires were analyzed. Only 13.85% of patients had no regrets at all about the decision, 34.60% experienced mild regret, and the proportion of patients with moderate to severe regrets reached 51.50%. Mild impact on life, active decision-making roles, passive decision-making roles, and decision conflict were the influencing factors of decisional regret in hepatitis B patients on pegylated interferon alpha therapy, which together explained 29.6% of the total variation. Hepatitis B patients undergoing pegylated interferon alpha therapy had a high percentage of decisional regret. Healthcare professionals should pay close attention to this phenomenon. In the future, they can investigate additional potential influencing factors and promptly develop intervention strategies to effectively reduce decision regret.

The 3' UTR Pseudoknot-Containing Region of Arteriviruses Acts as a PAMP to Activate RIG-I- and TLR8-Dependent Type I Interferon Responses.

Xie Sha S, Zhang Lu L, Sun Yan-Gang YG, Shu Meixin M

Porcine reproductive and respiratory syndrome virus (PRRSV) and other members of the Arteriviridae family cause substantial economic losses in livestock. However, their pathogen-associated molecular patterns (PAMPs) remain poorly characterized. Here, we investigated whether the 3' untranslated region (UTR) pseudoknot structures of Arteriviruses act as PAMPs and explored the underlying innate immune recognition mechanisms. Bioinformatics predictions (RNAalifold, RNArtist, and RNAComposer) revealed that the 3' UTR pseudoknot structures are conserved across all four Arteriviruses. In vitro transcribed pseudoknot RNAs significantly upregulated the mRNA expression of type I interferons (IFNα/β) and interferon-stimulated genes (protein kinase R, PKR; interferon-stimulated gene 15, ISG15; interferon-stimulated gene 56, ISG56) in Marc145 cells. Screening of RNA-sensing pattern recognition receptors (retinoic acid-inducible gene I, RIG-I; melanoma differentiation-associated protein 5, MDA5; Toll-like receptor 3/7/8/9, TLR3/7/8/9) in pseudoknot RNA-stimulated cells showed that RIG-I and TLR8 were significantly upregulated, whereas MDA5, TLR3, TLR7, and TLR9 were not. Short hairpin RNA (shRNA)-mediated knockdown of RIG-I or TLR8 significantly reduced pseudoknot-induced expression of IFNβ, PKR, and ISG56, confirming that both receptors are functionally required for this response. Upregulation of myeloid differentiation primary response 88 (MyD88), interferon regulatory factor 7 (IRF7), and signal transducer and activator of transcription 2 (STAT2) suggested that IFNα/β and downstream interferon-stimulated genes (ISGs) were induced via the TLR8-MyD88-IRF7 and RIG-I-IRF7 signaling pathways. Moreover, small-angle X-ray scattering (SAXS) analysis of the PRRSV pseudoknot RNA complexed with the porcine RIG-I regulatory domain was consistent with the formation of a complex between the pseudoknot RNA and RIG-I. In conclusion, this study identified the 3' UTR pseudoknot-containing region of Arteriviruses as a conserved PAMP that activates RIG-I- and TLR8-dependent type I IFN responses, providing a mechanistic basis and potential targets for antiviral therapy and vaccine adjuvant development against Arterivirus infections.

Interferon-α directs hematopoietic stem cells toward competing fates.

Rodriguez-Meira Alba A