Thymosin Alpha-1

Abstract

Aging is characterized by immune decline, mainly due to thymic involution-the age-related shrinkage of the thymus gland. This leads to reduced T-cell production, chronic inflammation, and increased susceptibility to age-related diseases. Thymosin alpha-1 (Tα1), a peptide hormone produced by the thymus, exhibits potent immunomodulatory, anti-inflammatory, and antioxidant properties. It helps restore immune function by stimulating T-cell differentiation, enhancing thymic output, and modulating dendritic cell and macrophage activity. Preclinical and clinical studies show that Tα1 can improve vaccine response in the elderly and mitigate immunosenescence. The hybrid drug Refnot (a fusion of tumor necrosis factor alpha (TNFα) and Tα1) combines Tα1's immunomodulation with TNF's antitumor activity but has reduced toxicity. It represents a promising therapeutic approach to counteract age-related immune dysfunction and inflammation, potentially by slowing the aging process. Further research is needed to validate its long-term efficacy and safety in geriatrics.

Abstract

Tooth pulpitis is a prevalent oral disorder. Understanding the underlying mechanisms of pulpitis and developing effective treatment strategies hold great significance. Ferroptosis has recently emerged as a new form of cell death, but the role of ferroptosis in pulpitis remains largely unknown. In our study, single-cell RNA sequencing (scRNA-seq) was used to identify cellular heterogeneity between 3 pulpitis tissue and 3 healthy pulp tissue, and explored ferroptosis occurrence in pulpitis tissue and inflamed dental pulp cells (DPCs). In scRNA-seq, 40 231 cells (Pulpitis: 17 814; Healthy pulp: 22 417) were captured, and visualized into 12 distinct cell clusters. Differentially expressed ferroptosis-related genes (DE-FRGs) were almost presented in each cluster in pulpitis vs healthy pulp. ROS and Fe2+ levels significantly rose, and immunohistochemistry showed low expression of GPX4 and high expression of PTGS2 in pulpitis. In LPS-stimulated DPCs, thymosin α1 increased the expression of GPX4 and FTL, and decreased expression of TNF-α, IL-1β, IL-6, and Fe2+ levels. In rat pulpitis models, both prothymosin α (PTMA, precursor of thymosin α1) gelatin sponge placed at the hole of pulp (LPS-P(gs)) and PTMA injection in pulp (LPS-P(i)) significantly reduced infiltration of inflammatory cells and expression of PTGS2, and increased the expression of GPX4. In RNA sequencing, the expression of DE-FRGs were reversed when thymosin α1 were added in LPS-stimulated DPCs. Collectively, single-cell atlas reveals cellular heterogeneity between pulpitis and healthy pulp, and ferroptosis occurrence in pulpitis. Thymosin α1 may reduce ferroptosis in DPCs to alleviate pulpitis and thus potentially has the ability to treat pulpitis.

Abstract

Aims/Background Immunotherapy plays a critical role in the clinical treatment of tuberculosis, an infectious disease caused by Mycobacterium tuberculosis, in which immune damage promotes the occurrence and development of the disease. This study aimed to investigate the efficacy of thymosin α1 combined with the 2HRZE/4HR (2 months of isoniazid, rifampin, pyrazinamide, and ethambutol followed by 4 months of isoniazid and rifampin) in the treatment of pulmonary tuberculosis and its effect on immune function and inflammatory factors. Methods A retrospective analysis was conducted on 106 pulmonary tuberculosis patients treated between October 2022 and June 2024. The patients were divided into two groups based on their treatment regimens: the control group (n = 47) received the 2HRZE/4HR treatment, while the observation group (n = 59) received thymosin α1 in addition to the 2HRZE/4HR treatment. All patients underwent a 6-month treatment course. Clinical efficacy was evaluated 6 months after treatment based on clinical symptoms and sputum smear results. The study compared foci resorption rates, cavity closure rates, and changes in pulmonary function indices, immune function indices, and inflammatory factor levels before and after treatment between the two groups. Adverse reactions were also recorded and analyzed. Results The total effective rate and the rate of foci resorption and cavity closure of the observation group were higher than the control group (p < 0.05). After 6 months of treatment, forced expiratory volume in one second (FEV1), forced vital capacity (FVC), FEV1/FVC, and peak expiratory flow (PEF) of the observation group were higher compared to the control group (p < 0.05). Compared with the control group, the observation group exhibited lower mRNA expression of T-cell immunoglobulin mucin-1 (TIM-1) and TIM-3; reduced levels of immunoglobulin E (IgE), sputum supernatant, serum interleukin-4 (IL-4) and tumor necrosis factor-alpha (TNF-α); but higher interferon-gamma (IFN-γ) levels (p < 0.05). There was no significant difference in the incidence of adverse reactions between the two groups (p > 0.05). Conclusion Thymosin α1 combined with the 2HRZE/4HR regimen holds promise as an effective treatment of pulmonary tuberculosis by improving immune function and pulmonary function of patients while attenuating the inflammatory response.

Abstract

Despite advances in understanding sepsis pathophysiology and extensive research, few treatments effectively target its underlying immune dysfunction. Thymosin α1 (Tα1) shows promise as an immunomodulator, but its impact on sepsis remains unclear.

Abstract

Immune and inflammatory disorders are part of the complex pathophysiological processes that exacerbate severe acute pancreatitis (SAP) and subsequent infection. Thymosin alpha 1 (Tα1) is an important immunomodulatory agent in clinical practice, but there is a lack evidence to prove its effectiveness in improving the condition of SAP patients. In this study, we aimed to evaluate the efficacy in meta-analysis.

Abstract

This multicenter randomized controlled trial evaluates the efficacy of thymosin alpha 1 (Tα1) supplementation in preventing organ dysfunction following acute type A aortic dissection (ATAAD) repair. Over 330 patients will be equally assigned to receive either Tα1 plus standard care or placebo with standard management. The primary endpoint involves calculating the difference in mean postoperative Sequential Organ Failure Assessment (SOFA) scores between groups, measured daily from postoperative days 7. By targeting post-operative immune system imbalance, this study aims to establish a novel therapeutic approach for reducing systemic inflammatory response syndrome (SIRS)-mediated organ injury and improving long-term outcomes in this high-risk population. Results will be disseminated through peer-reviewed publications and international conferences.Trial registration: ClinicalTrials.gov Registry (NCT05339529).

Abstract

To validate the efficacy and safety of thymosin α-1 combined with lenvatinib plus sintilimab in the treatment of unresectable hepatocellular carcinoma. Patients with unresectable hepatocellular carcinoma treated with lenvatinib plus sintilimab at the People's Hospital of Guangxi Zhuang Autonomous Region from January 2020 to June 2022 were retrospectively analyzed. The patients were divided into an experimental group and a control group based on their therapeutic regimens: thymosin α-1 plus lenvatinib and sintilimab (experimental group), and lenvatinib plus sintilimab (control group). The primary endpoints were overall survival and progression-free survival. Tumor response was evaluated according to mRECIST criteria, and the partial response, complete response, stable disease, progressive disease, object response rate, and disease control rate of the two groups were compared. Adverse events were evaluated using the Common Terminology Criteria for Adverse Events version 5.0. The median overall survival of all patients was 13.0 months (95% CI 10.587-15.413). The experimental group had a longer median overall survival than the control group (16 months vs. 11 months, P = 0.018). The median progression free survival of all patients was 5.0 months (95% CI 3.721-6.279). The experimental group had a longer median progression-free survival than the control group (7 months vs. 4 months, P = 0.006). The objective response rate of the experimental group was 55.8% (24/43), and of the control group's 34.7% (17/49) (P = 0.042). The disease control rate of the experimental group was 76.7% (33/43), while the control group had a rate of 59.2% (29/49) (P = 0.073). There was no significant difference in the incidence of grade 1-2 adverse events or grade 3-4 adverse events between the two groups (P > 0.05). Thymosin α-1 combined with lenvatinib plus sintilimab is an effective and safe therapeutic regimen in unresectable hepatocellular carcinoma.

Abstract

The fast-growing filed of long-acting depots for subcutaneous (SC) administration holds significant potential to enhance patient adherence to treatment regimens, particularly in the context of chronic diseases. Among them, injectable in situ forming lyotropic liquid crystals (LCCs) consisting of hexagonal mesophases represent an attractive platform due to their remarkable highly ordered microstructure enabling the sustained drug release. These systems are especially relevant for peptide drugs, as their use is limited by their short plasma half-life and inherent poor stability. In this study, we thus aimed to exploit the potential of a liquid crystalline platform for the sustained release of peptide drug thymosin alpha 1 (Tα1), characterized by a short plasma half-life and with that associated twice-weekly SC administration regimen. We initially selected specified ingredients, with ethanol serving to reduce viscosity and stabilize the peptide drug Tα1, lecithin contributing to LCCs formation and stabilization, and glycerol monooleate or glycerol monolinoleate representing the hexagonal LCCs forming matrix material. The selected studied nonaqueous precursor formulations were characterized by suitable rheological properties for SC injection. A convenient and rapid in situ phase transition of precursor formulations to hexagonal LCCs, triggered by water absorption, was successfully accomplished in vitro. Notably, in situ formed LCCs demonstrated sustained release kinetics of the peptide drug Tα1 for up to 2 weeks of in vitro release testing, offering minimized dosing frequency and thus promoting patient adherence. In summary, the newly developed in situ forming liquid crystalline systems represent prospective injectable long-acting depots for SC administration of the peptide drug Tα1.

Abstract

Sepsis, a multifaceted disorder, emerges from dysregulated host response to infection, culminating in organ dysfunction and heightened risk of mortality. Present umbrella systematic review was conducted to impart accurate data regarding the effect of urinary trypsin inhibitor (UTI) alone, UTI in combination with thymosin α1, and UTI in combination with Xuebijing on sepsis and inflammation, 28-day mortality rate survival day, time of mechanical ventilation, length of intensive care unit stay, and acute physiology and chronic health evaluation (APACHE II) score.