PEPITEM is an immune-modulatory peptide that effectively regulates inflammation and mitigates immune-mediated inflammatory diseases (IMIDs). Here, we identify two independently active tripeptide pharmacophores within PEPITEM and engineered peptidomimetics with enhanced pharmacodynamic properties. These peptidomimetics regulate T-cell trafficking in vitro and reduce T-cell, neutrophil and macrophage numbers in the inflamed peritoneal cavity in vivo. In a plaque psoriasis model, topical administration reduced disease severity, inflammation and immune cell infiltration, while regulating cytokine release in macrophages and fibroblasts, as well as keratinocyte proliferation. Th1 and Th17 cell abundance, along with their cytokines, was reduced in secondary lymphoid organs. This expanded functional repertoire of PEPITEM and its derivatives provides innovative tools for countering immune and stromal cell-induced pathology in IMIDs. Moreover, by identifying significantly smaller tripeptide pharmacophores of 14 amino acid PEPITEM, we may be able to deliver substantial financial advantages in synthesis and formulation. The order of magnitude increase in efficacy observed for some peptidomimetics may deliver agents with enhanced pharmacological characteristics compared to the parent PEPITEM sequence. Taken together with other reports on the efficacy of PEPITEM, this study paves the way for the development and translation of a novel class of anti-inflammatory agents which may have utility in a broad range of autoimmune and chronic inflammatory diseases.

Favipiravir displays a rapid viral clearance, a high recovery rate and broad therapeutic safety; however, its oral administration was associated with systemic side effects in susceptible patients. Considering that the pulmonary route could provide a high drug concentration, and a safer application with less absorption into systemic circulation, it was aimed to elucidate whether favipiravir delivered via soft-mist inhaler has any deleterious effects on lung, liver and kidney tissues of healthy rats. Wistar albino rats of both sexes (n = 72) were placed in restrainers, and were given either saline or favipiravir (1, 2.5, 5 or 10 mg/kg in 1 mL saline) by inhalation within 2 min for 5 consecutive days. On the 6th day, electrocardiographic recording was obtained, and cardiac blood and lung tissues were collected. Favipiravir did not alter cardiac rhythm, blood cell counts, serum levels of alanine transaminase, aspartate transaminase, blood urea nitrogen, creatinine, urea or uric acid, and did not cause any significant changes in the pulmonary malondialdehyde, myeloperoxidase activity or antioxidant glutathione levels. Our data revealed that pulmonary use of favipiravir via soft-mist inhaler enables a high local concentration compared to plasma without oxidative lung injury or cardiac or hepatorenal dysfunction.

Background: Preprints—scientific manuscripts shared publicly prior to formal peer review—are gaining momentum across academic disciplines. However, their adoption in clinical and biomedical sciences remains limited, particularly in countries where traditional publishing norms prevail. Editorial ambiguity and a lack of national policy further complicate their use. Objective: This study aimed to assess the awareness, experiences, and attitudes of medical academics at Marmara University School of Medicine toward preprints and to explore the editorial landscape through both journal editor feedback and a review of journal-level preprint policies. Methods: A cross-sectional survey was conducted with 103 medical faculty members. The questionnaire included demographic questions, Likert scale items, and multiple-choice items assessing knowledge, familiarity, and attitudes toward preprints, as well as open-ended items to explore concerns. A “preprint test score” (0‐4) was developed to quantify objective knowledge. Subgroup analyses were conducted by age (<40 vs ≥40 y) and academic discipline (basic vs clinical sciences). Additionally, all responses to open-ended questions from journal editors and 118 biomedical journals were manually reviewed for their stated stance on preprints and article processing charges (APCs). A convergent mixed methods design was used, combining a structured survey, thematic analysis of open-ended responses and editorial feedback, and a document-based review of biomedical journal policies. Results: Only 42.9% (n=34) of participants reported familiarity with the concept of preprints, and 13% (n=10) had previously published on a preprint server. Misconceptions about ethics, peer review, and compatibility with journal policies were common. Subgroup analysis revealed that older participants scored higher on the “preprint test” (mean 2.20, SD 1.31 vs mean 1.97, SD 1.60) and had more experience with preprint publishing (1/40, 2.5% of younger participants; 7/29, 24.1% of older participants). Further, younger academics expressed less openness toward future use (n=7, 17.5% in the younger group; n=8, 27.6% in the older group). Clinical faculty were generally more hesitant than basic science faculty, although both groups raised concerns about the academic recognition of preprints. Editorial responses reflected a mix of cautious endorsement and skepticism. Among the 118 biomedical journals reviewed, most lacked clear preprint policies, while a small number either explicitly prohibited or permitted them. Conclusions: There is limited awareness and cautious engagement with preprints among medical academics and editors in Türkiye. Generational and discipline-based differences further influence knowledge and attitudes. The lack of clear editorial guidance from biomedical journals may reinforce academic uncertainty. Tailored educational initiatives, transparent journal policies, and institutional support will be essential to foster a more open and inclusive scientific publishing environment.

Type 2 (T2) immunity is classically associated with defense against helminths and environmental threats, from a physiological perspective, and with allergies and eosinophilic inflammatory diseases, in a pathological sense. However, growing evidence reveals that T2 pathways also support other essential homeostatic functions, including tissue protection and repair. There are major clues from the early evolution of T2 responses for protection against massive tissue damage and positive selection for survival against parasites starting over 500 million years ago. These responses likely co‐evolved stepwise with immune‐regulatory circuits, culminating in the emergence of the fully functional human‐type IgG4 in the great apes (Hominidae) within the last ~10 million years. The involvement of body barriers along with the strong influence of local epithelial cells and their interaction with the microbiome and the immune system is a common characteristic of T2 inflammation. An expanding list of new T2 diseases is being reported, characterized by epithelial cell and immune system activation, epithelial barrier damage, and microbial dysbiosis, including opportunistic pathogen colonization and loss of commensals. This evolving understanding coincides with the clinical success of biologics targeting key T2 mediators such as IL‐4, IL‐5, IL‐13, IL‐31, TSLP, and IgE, which have transformed the management of severe allergic diseases and other T2‐driven pathologies. However, the contribution of T2 immunity to homeostatic programs raises questions about the long‐term consequences of sustained T2 suppression. In this review, we examine the dual role of T2 immunity in health and disease, revisit its evolutionary origins, highlight its protective functions beyond allergy, and discuss the potential implications of prolonged T2 pathway blockade.

PEPITEM is an immune-modulatory peptide that effectively regulates inflammation and mitigates immune-mediated inflammatory diseases (IMIDs). Here we identify two independently active tripeptide pharmacophores within PEPITEM and engineered peptidomimetics with enhanced pharmacodynamic properties. These peptidomimetics regulate T-cell trafficking in vitro and reduce T-cell, neutrophil and macrophage numbers in the inflamed peritoneal cavity i n vivo . In a plaque psoriasis model, topical administration reduced disease severity, inflammation and immune cell infiltration, while regulating cytokine release in macrophages and fibroblasts, as well as keratinocyte proliferation. Th1 and Th17 cell abundance, along with their cytokines, was reduced in secondary lymphoid organs. This expanded functional repertoire of PEPITEM and its derivatives provides innovative tools for countering immune and stromal cell-induced pathology in IMIDs, paving the way for a novel class of anti-inflammatory agents.