Search Results (66)

Background: Thymosin alpha 1 (Tα1, thymalfasin) is a thymus-derived immunomodulatory peptide investigated as an adjunctive therapy in cancer care. Although studied across malignancies, its evidence landscape has not been systematically mapped. This scoping review characterized treatment contexts, intervention patterns, outcome domains, and safety reporting of clinical studies evaluating Tα1 in patients with cancer. Methods: PubMed, Embase, and CENTRAL were searched for clinical studies of Tα1 in patients with cancer published from January 2016 to March 2026. Eligible studies included randomized controlled trials, non-randomized studies, observational studies, and case-based reports. Data on study characteristics, cancer type, intervention features, comparators, outcomes, and adverse-event reporting were charted and synthesized descriptively. Results: Twenty-six clinical publications were included. Most were conducted in China, and retrospective observational studies and case reports predominated. Hepatobiliary, thoracic, and gastrointestinal cancers were the most frequently studied clusters. Classical Tα1 was administered mainly by subcutaneous injection, most commonly at 1.6 mg, and used primarily as an adjunct to chemotherapy, radiotherapy, chemoradiotherapy, targeted therapy, immune checkpoint inhibitors, or postoperative and supportive care. Outcomes included tumor response, survival, recurrence, immune and inflammatory markers, treatment-related toxicity, functional status, and quality of life. Several studies reported favorable clinical, immune-related, or treatment-tolerance signals, but heterogeneity limited comparability. Safety reporting was inconsistent. One case described severe multisystem immune-related toxicity during combination treatment without establishing Tα1-specific causality. Conclusions: Tα1 has been investigated mainly as an adjunctive immunomodulatory strategy in cancer care. Prospective controlled studies with standardized dosing, defined treatment contexts, consistent outcomes, and systematic harms reporting are needed. Full article

Thymosin beta-4 (TB4) and the related compound commonly referred to as TB-500 are widely discussed in tissue healing and musculoskeletal medicine, but the scope and nature of the supporting literature remain unclear. We conducted a scoping review to map the evidence on TB4 and TB-500 in tissue healing, regeneration, and musculoskeletal repair. PubMed, Europe PMC, and ClinicalTrials.gov were searched through March 2026. English-language in vitro, animal, human, and registered clinical trial sources directly evaluating TB4, TB-500, or included derivatives in repair-related contexts were eligible. Of 1772 records identified, 80 studies were included. The evidence base was weighted toward mixed and in vitro designs, and most studies evaluated TB4 rather than TB-500. The most common tissue categories were wound/skin/soft tissue, vascular/endothelial, ocular/cornea, and bone. Direct musculoskeletal tissue categories such as tendon, ligament, muscle, cartilage, and spine/intervertebral disc were comparatively sparse. Human evidence was concentrated in ocular/cornea and wound/skin/soft tissue settings, whereas direct TB-500 evidence was limited to a single included study. Overall, the mapped literature supports the popular interest in several repair-related pathways but remains unevenly distributed and largely preclinical, with limited human evidence directly relevant to musculoskeletal applications. Full article

Background: Oxidative stress plays a key role in the pathogenesis of complications in preterm infants, including bronchopulmonary dysplasia (BPD). Thymosin β4 (Tβ4) and thymosin β10 (Tβ10) are proteins involved in tissue repair and responses to oxidative stress, but their role in extremely preterm neonates remains poorly understood. Methods: A total of 149 saliva samples from 18 infants with gestational age < 30 weeks were analyzed. Salivary proteins and their proteoforms were characterized using an integrated proteomic platform based on nano-HPLC-ESI-MS. Relative quantification was performed using extracted ion current (XIC) peak areas. Associations with postmenstrual age, oxygen requirement, and BPD development were assessed, including longitudinal analysis using generalized estimating equation (GEE) models. Results: Significant correlations were found between postmenstrual age and total Tβ4 (p = 0.001), oxidized Tβ4 percentage (p = 0.025), and total Tβ10 (p = 0.043). Higher oxygen requirement was associated with lower levels and percentages of oxidized Tβ10 (p = 0.005; p < 0.001). No significant differences were observed during the first week of life between neonates who later developed BPD and those who did not. However, longitudinal analysis showed that in neonates without BPD, total and oxidized Tβ10 and total Tβ4 increased over time, whereas in neonates with BPD, these biomarkers remained stable or decreased. The increase in oxidized Tβ10 percentage was slower in infants with BPD. Conclusions: Although no early differences were detected, longitudinal trajectories of Tβ4 and Tβ10 differed between infants with and without BPD. Postnatal changes in these proteins may be associated with differences in clinical course and exposure to postnatal oxidative stress. Full article

Endotoxemia represents a life-threatening clinical disorder driven by an aberrant host immune response to pathogenic infection, often resulting in severe multiple organ dysfunction. Among its most devastating complications are acute lung injury (ALI) and endotoxemia-associated encephalopathy (EAE), both of which are associated with elevated mortality and currently lack effective targeted interventions. This study evaluated the therapeutic efficacy and underlying molecular mechanisms of recombinant human thymosin β4 (rhTβ4) in a murine model of lipopolysaccharide (LPS)-induced endotoxemia. Our results showed that treatment with rhTβ4 markedly enhanced survival rates and diminished the systemic overproduction of diverse proinflammatory cytokines and chemokines in endotoxemic mice. These systemic protective actions were achieved through the inhibition of the TLR4/NF-κB signaling cascade, the reduction in M1 macrophage polarization, and the simultaneous alleviation of mitochondrial impairment and oxidative stress. Moreover, rhTβ4 treatment significantly rescued EAE-related cognitive deficits and attenuated neuronal damage, primarily through the suppression of neuroinflammation and microglial overactivation. Integrative transcriptomic profiling and functional assays identified lysophosphatidic acid receptor 3 (LPAR3) as an important contributor, suggesting that rhTβ4 suppresses microglial-mediated neurotoxicity at least in part through LPAR3 downregulation. In conclusion, rhTβ4 confers robust multi-organ protection against endotoxemic injury by orchestrating the inhibition of systemic and central neuroinflammatory cascades, positioning it as a promising candidate for the treatment of endotoxemia-induced ALI and EAE. Full article

Therapeutic peptides are short chains of amino acids used to treat metabolic and endocrine conditions such as obesity and type 2 diabetes. While several peptide drugs have undergone rigorous approval processes that evaluate both safety and efficacy, novel, unapproved compounds have emerged and are rapidly expanding into preventive medicine and performance enhancement. Our objective is to present the effects, clinical applications, safety profiles, and regulatory status of prominent peptides used to treat several conditions. We reviewed 106 articles, prioritizing systematic reviews, meta-analyses, and randomized controlled trials in the PubMed, ScienceDirect, and SciELO databases. Our results suggest that therapeutic peptides are a promising tool for treating type 2 diabetes and obesity, for skin rejuvenation, and as hormone analogs for specific diseases and conditions. Although these are strategic and innovative options that can improve health, performance, and longevity, further studies are needed before most new peptides can be used safely in humans. Full article

Thymosin β4 (Tβ4) is a highly acidic, intrinsically disordered 43-amino-acid peptide with diverse biological functions, yet its interactions with metal ions remain poorly understood. In this study, we provide the first experimental demonstration that Tβ4 forms discrete Zn²⁺-bound adducts and undergoes Zn²⁺-induced aggregation under physiological pH conditions. Combining zeta potential analysis, dynamic light scattering (DLS), electrospray ionization mass spectrometry (ESI-MS), nuclear magnetic resonance (NMR) spectroscopy, and scanning electron microscopy with elemental mapping (SEM/EDS), we show that Zn(II) binding progressively neutralizes Tβ4’s negative surface charge and triggers a sharp aggregation transition. ESI-MS unambiguously identifies Tβ4/Zn(II) complexes of peptide-to-zinc molar ratio 1:3, while DLS and SEM reveal the formation of compact, low-solubility supramolecular assemblies. NMR measurements support a metal-induced aggregation, confirming the absence of folding upon Zn(II) binding. By quantitatively comparing the experimentally determined critical aggregation concentration with physiologically observed extracellular Zn(II) ranges, we demonstrate that aggregation is unlikely in plasma or basal interstitial environments but may become feasible in Zn-rich microdomains, such as the synaptic cleft, where transient Zn(II) levels can exceed 1 μM. These findings introduce a previously unrecognized dimension of Tβ4 chemistry and suggest that a Zn(II)-mediated supramolecular assembly of Tβ4 could influence peptide behavior in neurological or inflammatory conditions characterized by elevated extracellular Zn(II). This work establishes a foundational biochemical framework for future studies aimed at elucidating the biological implications of Tβ4/Zn(II) complexation and aggregation in vivo. Full article

The thymus and parathyroid glands share a common embryological origin from the third pharyngeal pouch, yet their potential morphological and functional interconnections remain insufficiently explored. We conducted a comparative study integrating immunohistochemistry (IHC) and SEM on human thymic tissue, parathyroid adenomas, and parathyroid tissue excised during thyroidectomy. IHC staining targeted Thymosin-α1, CaSR, and PTH1R, with semi-quantitative evaluation of staining intensity and distribution. SEM analysis was performed at multiple magnifications to assess stromal organization and microvascular relief. Non-parametric statistical tests (Kruskal–Wallis with Mann–Whitney post hoc comparisons) were applied to clinical and laboratory data across the three cohorts. Scanning electron microscopy (SEM) revealed convergent ultrastructural features between thymus and parathyroid, including reticular stromal meshes and vascular grooves suggestive of comparable microcirculatory organization. IHC demonstrated robust Thymosin expression in thymus, with heterogeneous/apical distribution in parathyroid tissue; CaSR showed strong membranous and cytoplasmic expression in parathyroid, but weak diffuse signal in thymus; PTH1R exhibited low-to-moderate expression in thymus and moderate heterogeneous expression in parathyroid, with apical accentuation in adenomas. Statistical analysis confirmed significant differences in ionized calcium, PTH, and anti-AChR titers among the three cohorts (all p < 0.001), while TSH and calcitonin did not differ significantly. Our findings strengthen the hypothesis of a morpho-functional parathyroid–thymus axis. The robust parathyroid expression of CaSR and PTH1R aligns with established roles in calcium–PTH homeostasis, while the novel detection of Thymosin in parathyroid tissue suggests an expanded functional repertoire. These results highlight a continuum between embryological proximity and adult tissue cross-talk, with potential clinical implications for parathyroid pathology and immune regulation. Full article

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. Full article

Tunneling nanotubes (TNTs) are dynamic, actin-based intercellular structures that facilitate the transfer of organelles, including mitochondria, between cells. Unlike other protrusive structures such as filopodia and cytonemes, TNTs exhibit structural heterogeneity and functional versatility, enabling both short- and long-range cargo transport. This review explores the mechanisms underlying mitochondrial transfer via TNTs, with a particular focus on cytoskeletal dynamics and the role of key regulatory proteins such as Miro1, GFAP, MICAL2PV, CD38, Connexin 43, M-Sec, thymosin β4, and Talin 2. Miro1 emerges as a central mediator of mitochondrial trafficking, linking organelle motility to cellular stress responses and tissue repair. We delve into the translational implications of TNTs-mediated mitochondrial exchange in regenerative medicine and oncology, highlighting its potential to restore bioenergetics, mitigate oxidative stress, and reprogram cellular states. Despite growing interest, critical gaps remain in understanding the molecular determinants of TNT formation, the quality and fate of transferred mitochondria, and the optimal sources for mitochondrial isolation. Addressing these questions will be essential for harnessing TNTs and mitochondrial transplantation as therapeutic tools. Full article

The aim of this study was to achieve the high secretion and expression of thymosin β4 derived from Pinctada fucata in Pichia pastoris, as well as to investigate its antibacterial properties and biological effects in promoting wound healing. The recombinant thymosin β4 protein (rTβ4) exhibited no hemolytic activity on rabbit red blood cells and demonstrated significant antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA), with a minimum inhibitory concentration (MIC) of 25 μg/mL. It effectively inhibited bacterial growth and disrupted the cell wall and membrane structure of the bacteria. In the Sprague Dawley (SD) rat wound healing model, the wound healing rate in the rTβ4 treatment groups (at concentrations of 12.5 and 25 μg/mL) was significantly higher than that in the control group (p < 0.05), and the healing effect was comparable to that of the positive control group (Kangfu Xin solution, KFX). The histopathological study demonstrated that rTβ4 could reduce the infiltration of inflammatory cells and promote the proliferation and re-epithelialization of granulation tissue. In conclusion, this study successfully achieved the high expression of thymosin β4 derived from Pinctada fucata in Pichia pastoris and validated its antibacterial and wound healing potential through both In vitro and In vivo experiments. Full article

Although a myocardial infarction occurs roughly every minute in the U.S. alone, medical research has yet to unlock the key to fully enabling post-hypoxic myocardial regeneration. Thymosin beta-4 (TB4), a short, secreted peptide, was shown to possess a beneficial impact regarding myocardial cell survival, coronary re-growth and progenitor cell activation following myocardial infarction in adult mammals. It equally reduces scarring, however, the precise mechanisms through which the peptide assists this phenomenon have not been properly elucidated. Accordingly, the primary aim of our study was to identify novel molecular contributors responsible for the positive impact of TB4 during the remodeling processes of the infarcted heart. We performed miRNA profiling on adult mice hearts following permanent coronary ligation with or without systemic TB4 injection and searched for targets and novel mechanisms through which TB4 may mitigate pathological scarring in the heart. Our results revealed a significant increase in miR139-5p expression and identified ROCK1 as a potential target protein aligned. Real-time PCR, Western blot and immunostaining on adult mouse hearts and human cardiac cells revealed the peptide indirectly or directly modulates ROCK1 protein levels both in vivo and in vitro. We equally discovered TB4 may reverse or inhibit fibroblast/myofibroblast transformation and the potential downstream mechanisms by which TB4 alters cellular responses through ROCK1 are cell type specific. Given the beneficial effects of ROCK1 inhibition in various cardiac pathologies, we propose a potential utilization for TB4 as a ROCK1 inhibitor in the future. Full article

Background/Objectives: Tumor cell migration depends on the actin cytoskeleton modified by actin-binding proteins (ABPs). Overexpression of cofilin or thymosin beta4 (Tß4) has been correlated with an increase or decrease in their migratory activity, respectively. Methods: Immunostaining of tumor cells and transfection with EGFP-tagged cofilin or bicistronic vectors leading to independent expression of EGFP and Tß4. Determination of cell migration by transwell or agarose drop assay. Results: We modulated by transfection the intracellular concentrations of cofilin and Tß4 of two colon (3LNLN and EB3) and one breast carcinoma (MDA-MB-231) cell line and analyzed their migratory activity. Increasing wild-type cofilin did not alter their migratory activity, whereas the constitutively active S3A–cofilin mutant elevated migration. Transfection leading to an up- or downregulation of Tß4 showed that MDA-MB-231 and 3LNLN cells responded with a decrease or increase in migration, respectively. Exposure of MDA-MB-231 and 3LNLN cells to increasing concentrations of extracellular Tβ4 (or His-tagged Tß4) induced a biphasic response of migration, being highest around 0.24 µM and decreased at higher extracellular Tß4. Immunostaining of 3LNLN cells exposed to 0.24 µM extracellular His-tagged Tß4 with anti-His antibody indicated its uptake co-localizing with integrin-linked kinase at cell attachment points. Furthermore, the exposure to 0.24 µM His-tagged Tß4 led to increased phosphorylation of AKT1/2 and secretion of matrix metalloproteases. These effects and tumor cell migration were abrogated after exposure of 3LNLN cells to 2.8 µM His-Tß4, also inducing apoptosis in a number of cells. Conclusions: Tumor cell migration can be inhibited by high extracellular Tß4. Full article

Persistent corneal epithelial defects (PCEDs) are a challenging ocular condition characterized by the failure of complete corneal epithelial healing after an insult or injury, even after 14 days of standard care. There is a lack of therapeutics that target this condition and encourage re-epithelialization of the corneal surface in a timely and efficient manner. This review aims to provide an overview of current standards of management for PCEDs, highlighting novel, emerging treatments in this field. While many of the current non-surgical treatments aim to provide lubrication and mechanical support, novel non-surgical approaches are undergoing development to harness the proliferative and healing properties of human mesenchymal stem cells, platelets, lufepirsen, hyaluronic acid, thymosin ß4, p-derived peptide, and insulin-like growth factor for the treatment of PCEDs. Novel surgical treatments focus on corneal neurotization and limbal cell reconstruction using novel scaffold materials and cell-sources. This review provides insights into future PCED treatments that build upon current management guidelines. Full article

Although peptides have been shown to have biological functions in neurodegenerative diseases, their role in Parkinson’s disease has been understudied. A previous study by our group, which used a 6-hydroxydopamine zebrafish model, suggested that nine intracellular peptides may play a part in this condition. In this context, our aim is to better understand the role of five of these nine peptides. The selection of peptides was made based on their precursor proteins, which are fatty acid binding protein 7, mitochondrial ribosomal protein S36, MARCKS-related protein 1-B, excitatory amino acid transporter 2 and thymosin beta-4. The peptides were chemically synthesized in solid phase and characterized by high-performance liquid chromatography and mass spectrometry. Circular dichroism was performed to determine the secondary structure of each peptide, which showed that all five peptides maintain a random structure in the aqueous solutions that were studied. Two molecules show a helical profile in trifluoroethanol, a known structuring agent. Cell viability by the MTT assay indicates that all five peptides are not cytotoxic in all concentrations tested in both mouse and human cell lines. Behavioral assay using a 6-OHDA zebrafish larvae model suggest that all peptides help in the recovery of motor function with 24 h treatment at two concentrations. Three peptides showed a complete recovery from the 6-OHDA-induced motor impairment. Further studies are needed to better understand the mechanism of action of these peptides and whether they are truly a potential ally against Parkinson’s disease. Full article

Cardiac development is a complex developmental process. The early cardiac straight tube is composed of an external myocardial layer and an internal endocardial lining. Soon after rightward looping, the embryonic heart becomes externally covered by a new epithelial lining, the embryonic epicardium. A subset of these embryonic epicardial cells migrate and colonize the embryonic myocardium, contributing to the formation of distinct cell types. In recent years, our understanding of the molecular mechanisms that govern proepicardium and embryonic epicardium formation has greatly increased. We have recently witnessed the discovery of a novel layer of complexity governing gene regulation with the discovery of non-coding RNAs. Our laboratory recently identified three distinct lncRNAs, adjacent to the Wt1, Bmp4 and Fgf8 chicken gene loci, with enhanced expression in the proepicardium that are distinctly regulated by Bmp, Fgf and thymosin β4, providing support for their plausible implication in epicardial formation. The expression of lncRNAs was analyzed in different chicken and mouse tissues as well as their subcellular distribution in chicken proepicardial, epicardial, ventricle explants and in different murine cardiac cell types. lncRNA transcriptional regulation was analyzed by using siRNAs and expression vectors of different transcription factors in chicken and mouse models, whereas antisense oligonucleotides were used to inhibit Gm14014 expression. Furthermore, RT-qPCR, immunocytochemistry, RNA pulldown, Western blot, viability and cell migration assays were conducted to investigate the biological functions of Wt1_76127 and Gm14014. We demonstrated that Wt1_76127 in chicken and its putative conserved homologue Gm14014 in mice are widely distributed in different embryonic and adult tissues and distinctly regulated by cardiac-enriched transcription factors, particularly Mef2c and Nkx2.5. Furthermore, silencing assays demonstrated that mouse Gm14014, but not chicken Wt1_76127, is essential for epicardial, but not endocardial or myocardial, cell migration. Such processes are governed by partnering with Myl9, promoting cytoskeletal remodeling. Our data show that Gm14014 plays a pivotal role in epicardial cell migration essential for heart regeneration under these experimental conditions. Full article