Animal only
This mouse study investigated whether adjunctive thymosin beta-4 (Tβ4) combined with the antibiotic ciprofloxacin could restore corneal nerve integrity and visual function following Pseudomonas aeruginosa bacterial keratitis, a serious eye infection. Researchers induced keratitis in C57BL/6 mice by inoculating wounded corneas with P. aeruginosa, then administered one of four topical treatments three times daily beginning 24 hours post-infection: PBS (vehicle control), Tβ4 alone, ciprofloxacin alone, or Tβ4 combined with ciprofloxacin. Outcomes assessed included clinical disease severity, visual acuity, contrast sensitivity, corneal sensitivity (nerve function), and corneal nerve density/architecture via β-III tubulin immunofluorescence. The study found that the combination of Tβ4 and ciprofloxacin outperformed all monotherapy and control groups across every measured outcome, restoring nerve density and visual function to levels comparable to uninfected controls. Key limitations include the exclusive use of an animal model, meaning findings may not directly translate to humans, and the study does not address long-term safety, optimal treatment windows, or clinical feasibility. These results suggest Tβ4 may be a promising adjunctive therapy warranting further investigation.
Investigative ophthalmology & visual science · Jun 2026DOI ↗ Animal only
This study investigated a novel hydrogel-based therapy for intrauterine adhesions (IUA), a condition where uterine scarring causes infertility. The researchers engineered a hydrogel combining two components: a bioactive extracellular matrix derived from decidualized endometrium (DEndo-UdECM) and the anti-fibrotic peptide Thymosin β4 (Tβ4), designed for sustained local release. Using a mouse model of IUA, the study reported that a single administration of the hydrogel restored normal endometrial tissue architecture, reduced fibrosis, and resulted in near-complete fertility recovery in treated animals. Mechanistic investigations suggested the hydrogel worked by shifting macrophage polarization toward an anti-inflammatory M2 phenotype, suppressing pyroptosis-driven inflammation, and inhibiting the TGF-β/Smad3 signaling pathway, which drives fibrotic scarring. The study's primary limitation is that all experimental work was conducted in a murine model, meaning the findings have not yet been validated in humans or large-animal models. Whether the regenerative and anti-fibrotic effects, as well as the fertility outcomes, would translate to human patients remains unknown. Nonetheless, the study provides a mechanistically detailed preclinical proof-of-concept for a biomaterial strategy targeting the root pathology of IUA.
Nature communications · Jan 2026DOI ↗ Animal only
This study developed a novel low-temperature fabrication method for soluble microneedles (MNs) loaded with thymosin β4 (Tβ4), a peptide with known wound-healing and immunomodulatory properties. Traditional MN production methods involve conditions that can denature sensitive peptides, so the researchers used chitosan and sucrose to create stable, biocompatible MNs at lower temperatures. The resulting patches demonstrated uniform morphology, a high drug-loading capacity (~248 µg/patch), and rapid dissolution within one hour. In a mouse wound model, Tβ4-loaded MNs significantly enhanced wound healing compared to controls. To investigate the underlying mechanism, the study employed RNA sequencing and differentially expressed gene (DEG) analysis, identifying downregulated immune regulators Spp1, Vsig4, and IL22rα2 as potentially relevant targets. Subsequent in vitro experiments — including qPCR, western blot, and surface plasmon resonance (SPR) — demonstrated that Tβ4 specifically binds to Vsig4 (KD = 3.56 × 10⁻⁶ M) and IL22rα2 (KD = 9.69 × 10⁻⁶ M). A key limitation is that efficacy and mechanistic data are primarily derived from mouse models and cell-based assays, with no human clinical data reported. The findings offer insights into Tβ4's immunomodulatory targets and potential avenues for drug development.
Advanced healthcare materials · Dec 2025DOI ↗ Animal only
This study developed a multifunctional injectable hydrogel platform — called Exo@Tβ4/HAMA — designed to accelerate bone repair by simultaneously promoting stem cell recruitment, angiogenesis, neurogenesis, and osteogenesis. The hydrogel was fabricated by grafting Thymosin β4 (Tβ4), a short tissue-repair peptide, onto methylmalonic anhydride-modified hyaluronic acid (HAMA) via photo-cross-linking, then loading it with bone marrow mesenchymal stem cell (BMSC)-derived exosomes. In vitro experiments showed the hydrogel had favorable mechanical properties, good biocompatibility, and could recruit BMSCs, enhance tube formation in human umbilical vein endothelial cells (HUVECs), and promote osteogenic differentiation. In vivo rat cranial defect models demonstrated that the hydrogel promoted new bone formation, vascularization, and nerve ingrowth. The study identified the ERK1/2-dependent RUNX2 signaling pathway as a likely mechanistic contributor to osteogenesis. Key limitations include exclusive use of rat models with no human data, a relatively short observation window, and lack of comparison to current clinical gold-standard grafts. The findings suggest promise as a cell-free, injectable bone regeneration scaffold, but clinical translation requires further validation.
Animal only
This study investigated whether Thymosin β4 (Tβ4), a bioactive polypeptide, could regulate liver inflammation in nonalcoholic fatty liver disease (NAFLD) by influencing macrophage polarization. Researchers used a mouse model of NAFLD induced by a methionine and choline-deficient (MCD) diet in C57 mice, with liver Tβ4 knocked down via tail-vein-injected siRNA. Macrophage involvement was assessed using clodronate liposome depletion. Additionally, in vitro experiments co-cultured THP-1 macrophage cells with oleic acid-treated LO2 hepatocytes at varying Tβ4 concentrations. The study found that Tβ4 treatment was associated with reduced liver inflammation and steatosis in mice, while Tβ4 knockdown worsened steatosis. Tβ4 appeared to shift macrophages toward an M2 (anti-inflammatory) phenotype, reduce M1 marker expression, decrease hepatocyte apoptosis, downregulate STAT1 phosphorylation, and increase SOCS1/3 expression. A publicly available dataset was also used to assess Tβ4 expression in hepatocellular carcinoma-adjacent fatty tissue. Limitations include reliance primarily on animal and in vitro models, a relatively small experimental scope, and no direct human clinical data, leaving the translational relevance of these findings uncertain.
Journal of inflammation research · Apr 2025DOI ↗ Animal only
This study investigated whether inhaled recombinant human thymosin beta 4 (rhTβ4), delivered via nebulization, could reduce pulmonary fibrosis in a mouse model. Researchers induced pulmonary fibrosis in mice using bleomycin and then administered rhTβ4 aerosols at three different time points: early, mid-term, and late stages of fibrosis development. Efficacy was assessed through hydroxyproline content (a marker of collagen deposition), lung function measurements, and histopathological examination of lung tissue. The study found that nebulized rhTβ4 was associated with reduced fibrosis markers across all three dosing strategies. In parallel cell-based experiments, rhTβ4 appeared to suppress lung fibroblast proliferation, migration, and activation, and to inhibit epithelial-mesenchymal transition (EMT) in pulmonary epithelial cells, with both effects linked to modulation of the TGF-β1 signalling pathway. Limitations include the exclusive use of a mouse bleomycin model (which incompletely recapitulates human IPF), the absence of human clinical data, and the lack of direct mechanistic confirmation in vivo. The authors conclude that nebulized rhTβ4 warrants further investigation as a potential therapy for idiopathic pulmonary fibrosis.
The Journal of pharmacy and pharmacology · Apr 2025DOI ↗