-
Frontiers in Immunology 2023Cancer is one of the leading causes of death worldwide. The burden of cancer on public health is becoming more widely acknowledged. Lung cancer has one of the highest... (Review)
Review
Cancer is one of the leading causes of death worldwide. The burden of cancer on public health is becoming more widely acknowledged. Lung cancer has one of the highest incidence and mortality rates of all cancers. The prevalence of early screening, the emergence of targeted therapy, and the development of immunotherapy have all significantly improved the overall prognosis of lung cancer patients. The current state of affairs, however, is not encouraging, and there are issues like poor treatment outcomes for some patients and extremely poor prognoses for those with advanced lung cancer. Because of their potent immunomodulatory capabilities, thymosin drugs are frequently used in the treatment of tumors. The effectiveness of thymosin drugs in the treatment of lung cancer has been demonstrated in numerous studies, which amply demonstrates the potential and future of thymosin drugs for the treatment of lung cancer. The clinical research on thymosin peptide drugs in lung cancer and the basic research on the mechanism of thymosin drugs in anti-lung cancer are both systematically summarized and analyzed in this paper, along with future research directions.
Topics: Humans; Lung Neoplasms; Immunotherapy; Immunomodulation; Public Health; Thymosin
PubMed: 37701432
DOI: 10.3389/fimmu.2023.1237978 -
Frontiers in Endocrinology 2021Thymosin β4 (Tβ4) is a multifunctional and widely distributed peptide that plays a pivotal role in several physiological and pathological processes in the body,... (Review)
Review
Thymosin β4 (Tβ4) is a multifunctional and widely distributed peptide that plays a pivotal role in several physiological and pathological processes in the body, namely, increasing angiogenesis and proliferation and inhibiting apoptosis and inflammation. Moreover, Tβ4 is effectively utilized for several indications in animal experiments or clinical trials, such as myocardial infarction and myocardial ischemia-reperfusion injury, xerophthalmia, liver and renal fibrosis, ulcerative colitis and colon cancer, and skin trauma. Recent studies have reported the potential application of Tβ4 and its underlying mechanisms. The present study reveals the progress regarding functions and applications of Tβ4.
Topics: Animals; Apoptosis; Humans; Inflammation; Signal Transduction; Thymosin
PubMed: 34992578
DOI: 10.3389/fendo.2021.767785 -
Molecules (Basel, Switzerland) Apr 2023Thymosin α1 (Tα1) is an immunostimulatory peptide that is commonly used as an immune enhancer in viral infectious diseases such as hepatitis B, hepatitis C, and... (Review)
Review
Thymosin α1 (Tα1) is an immunostimulatory peptide that is commonly used as an immune enhancer in viral infectious diseases such as hepatitis B, hepatitis C, and acquired immune deficiency syndrome (AIDS). Tα1 can influence the functions of immune cells, such as T cells, B cells, macrophages, and natural killer cells, by interacting with various Toll-like receptors (TLRs). Generally, Tα1 can bind to TLR3/4/9 and activate downstream IRF3 and NF-κB signal pathways, thus promoting the proliferation and activation of target immune cells. Moreover, TLR2 and TLR7 are also associated with Tα1. TLR2/NF-κB, TLR2/p38MAPK, or TLR7/MyD88 signaling pathways are activated by Tα1 to promote the production of various cytokines, thereby enhancing the innate and adaptive immune responses. At present, there are many reports on the clinical application and pharmacological research of Tα1, but there is no systematic review to analyze its exact clinical efficacy in these viral infectious diseases via its modulation of immune function. This review offers an overview and discussion of the characteristics of Tα1, its immunomodulatory properties, the molecular mechanisms underlying its therapeutic effects, and its clinical applications in antiviral therapy.
Topics: Humans; Thymalfasin; Thymosin; NF-kappa B; Toll-Like Receptor 2; Toll-Like Receptor 7; Acquired Immunodeficiency Syndrome
PubMed: 37110771
DOI: 10.3390/molecules28083539 -
Cardiovascular Research May 2023The adult mammalian heart is a post-mitotic organ. Even in response to necrotic injuries, where regeneration would be essential to reinstate cardiac structure and...
AIMS
The adult mammalian heart is a post-mitotic organ. Even in response to necrotic injuries, where regeneration would be essential to reinstate cardiac structure and function, only a minor percentage of cardiomyocytes undergo cytokinesis. The gene programme that promotes cell division within this population of cardiomyocytes is not fully understood. In this study, we aimed to determine the gene expression profile of proliferating adult cardiomyocytes in the mammalian heart after myocardial ischaemia, to identify factors to can promote cardiac regeneration.
METHODS AND RESULTS
Here, we demonstrate increased 5-ethynyl-2'deoxyuridine incorporation in cardiomyocytes 3 days post-myocardial infarction in mice. By applying multi-colour lineage tracing, we show that this is paralleled by clonal expansion of cardiomyocytes in the borderzone of the infarcted tissue. Bioinformatic analysis of single-cell RNA sequencing data from cardiomyocytes at 3 days post ischaemic injury revealed a distinct transcriptional profile in cardiomyocytes expressing cell cycle markers. Combinatorial overexpression of the enriched genes within this population in neonatal rat cardiomyocytes and mice at postnatal day 12 (P12) unveiled key genes that promoted increased cardiomyocyte proliferation. Therapeutic delivery of these gene cocktails into the myocardial wall after ischaemic injury demonstrated that a combination of thymosin beta 4 (TMSB4) and prothymosin alpha (PTMA) provide a permissive environment for cardiomyocyte proliferation and thereby attenuated cardiac dysfunction.
CONCLUSION
This study reveals the transcriptional profile of proliferating cardiomyocytes in the ischaemic heart and shows that overexpression of the two identified factors, TMSB4 and PTMA, can promote cardiac regeneration. This work indicates that in addition to activating cardiomyocyte proliferation, a supportive environment is a key for regeneration to occur.
Topics: Mice; Animals; Rats; Cell Proliferation; Heart; Myocytes, Cardiac; Heart Injuries; Thymosin; Regeneration; Mammals
PubMed: 36125329
DOI: 10.1093/cvr/cvac155 -
Expert Opinion on Biological Therapy Jul 2018Sepsis is the dysregulated host response to an infection resulting in life-threatening organ damage. Thymosin Beta 4 is an actin binding protein that inhibits the... (Review)
Review
INTRODUCTION
Sepsis is the dysregulated host response to an infection resulting in life-threatening organ damage. Thymosin Beta 4 is an actin binding protein that inhibits the polymerization of G-actin into F-actin and improves mortality when administered intravenously to septic rats. Thymosin Beta 4 decreases inflammatory mediators, lowers reactive oxygen species, up-regulates anti-oxidative enzymes, anti-inflammatory genes, and anti-apoptotic enzymes making it an interesting protein to study in sepsis.
AREAS COVERED
The authors summarize the current knowledge of actin and Thymosin Beta 4 as it relates to sepsis via a comprehensive literature search.
EXPERT OPINION
Sepsis results in measurable levels of F-actin in the circulation as well as a decreased concentration of Thymosin Beta 4. It is speculated that F-actinemia contributes to microcirculatory perturbations present in patients with sepsis by disturbing laminar flow. Given that Thymosin Beta 4 inhibits the polymerization of F-actin, it is possible that Thymosin Beta 4 decreases mortality in sepsis via the regulation of actin as well as its other anti-inflammatory properties and should be further pursued as a clinical trial in humans with sepsis.
Topics: Actins; Animals; Humans; Microcirculation; Oxidation-Reduction; Rats; Reactive Oxygen Species; Sepsis; Thymosin
PubMed: 29508629
DOI: 10.1080/14712598.2018.1448381 -
Journal of Cell Science Jan 2018Globular (G)-actin, the actin monomer, assembles into polarized filaments that form networks that can provide structural support, generate force and organize the cell.... (Review)
Review
Globular (G)-actin, the actin monomer, assembles into polarized filaments that form networks that can provide structural support, generate force and organize the cell. Many of these structures are highly dynamic and to maintain them, the cell relies on a large reserve of monomers. Classically, the G-actin pool has been thought of as homogenous. However, recent work has shown that actin monomers can exist in distinct groups that can be targeted to specific networks, where they drive and modify filament assembly in ways that can have profound effects on cellular behavior. This Review focuses on the potential factors that could create functionally distinct pools of actin monomers in the cell, including differences between the actin isoforms and the regulation of G-actin by monomer binding proteins, such as profilin and thymosin β4. Owing to difficulties in studying and visualizing G-actin, our knowledge over the precise role that specific actin monomer pools play in regulating cellular actin dynamics remains incomplete. Here, we discuss some of these unanswered questions and also provide a summary of the methodologies currently available for the imaging of G-actin.
Topics: Actins; Animals; Cytoskeleton; Humans; Kinetics; Models, Molecular; Profilins; Thymosin
PubMed: 29321224
DOI: 10.1242/jcs.203760 -
BioMed Research International 2016Objective. To systematically review the efficacy and potential immunomodulatory effect of ulinastatin combined with thymosin α1 (UTI) for sepsis. Design. A systematic... (Meta-Analysis)
Meta-Analysis Review
Objective. To systematically review the efficacy and potential immunomodulatory effect of ulinastatin combined with thymosin α1 (UTI) for sepsis. Design. A systematic review and meta-analysis of randomized controlled trials (RCTs). Data Sources. The following databases: PubMed, Embase, and Cochrane Central were searched to identify related clinical trials. The search terms were "ulinastatin", "thymosin", and "sepsis". Results. Six RCTs, 944 septic patients in total, were included in this meta-analysis. The result shows UTI increased the 28-day survival rate of septic patients, odds ratio (OR) = 2.01, 95% CI [1.53, 2.64]. After the treatment with UTI, the APACHE II score (four studies) dropped 4.72 further, mean = -4.72, 95% CI [-6.54, -2.91] (p < 0.00001). The mean time of ICU stay (four studies) in UTI group decreased 3.03 days further, mean = -3.03 [-6.99, 0.95] (p = 0.14), and mechanical ventilation time (four studies) decreased 2.05 days, mean = -1.81 [-2.96, -0.66] (p = 0.002). With the treatment of UTI, CD4+T cells raised 5.13%, mean = 5.13, 95% CI [2.75, 7.50] (p < 0.0001); there was no significant change in CD8+T cells, mean = -0.74 [-2.93, 1.45] (p = 0.51). Conclusion. According to this meta-analysis, with the treatment of UTI, the short-term survival rate of septic patients was increased and the illness severity was alleviated. ICU stay and mechanical ventilation time were effectively shortened. The beneficial effect of UTI might be due to the potential immunomodulatory effects of these two drugs.
Topics: Adult; Aged; Aged, 80 and over; Causality; Comorbidity; Female; Glycoproteins; Humans; Immunologic Factors; Male; Middle Aged; Prevalence; Randomized Controlled Trials as Topic; Respiration, Artificial; Respiratory Insufficiency; Risk Factors; Sepsis; Survival Rate; Thymalfasin; Thymosin; Treatment Outcome
PubMed: 27340674
DOI: 10.1155/2016/9508493 -
Journal of Cellular and Molecular... Feb 2021The hair follicle (HF) is an important mini-organ of the skin, composed of many types of cells. Dermal papilla cells are important signalling components that guide the... (Review)
Review
The hair follicle (HF) is an important mini-organ of the skin, composed of many types of cells. Dermal papilla cells are important signalling components that guide the proliferation, upward migration and differentiation of HF stem cell progenitor cells to form other types of HF cells. Thymosin β4 (Tβ4), a major actin-sequestering protein, is involved in various cellular responses and has recently been shown to play key roles in HF growth and development. Endogenous Tβ4 can activate the mouse HF cycle transition and affect HF growth and development by promoting the migration and differentiation of HF stem cells and their progeny. In addition, exogenous Tβ4 increases the rate of hair growth in mice and promotes cashmere production by increasing the number of secondary HFs (hair follicles) in cashmere goats. However, the molecular mechanisms through which Tβ4 promotes HF growth and development have rarely been reported. Herein, we review the functions and mechanisms of Tβ4 in HF growth and development and describe the endogenous and exogenous actions of Tβ4 in HFs to provide insights into the roles of Tβ4 in HF growth and development.
Topics: Animals; Gene Expression Regulation; Growth and Development; Hair Follicle; Humans; Organogenesis; Signal Transduction; Structure-Activity Relationship; Thymosin
PubMed: 33393222
DOI: 10.1111/jcmm.16241 -
International Journal of Molecular... Oct 2022Fibrosis is a pathological process in which parenchymal cells are necrotic and excess extracellular matrix (ECM) is accumulated due to dysregulation of tissue injury... (Review)
Review
Fibrosis is a pathological process in which parenchymal cells are necrotic and excess extracellular matrix (ECM) is accumulated due to dysregulation of tissue injury repair. Thymosin β4 (Tβ4) is a 43 amino acid multifunctional polypeptide that is involved in wound healing. Prolyl oligopeptidase (POP) is the main enzyme that hydrolyzes Tβ4 to produce its derivative N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) which is found to play a role in the regulation of fibrosis. Accumulating evidence suggests that the Tβ4-POP-Ac-SDKP axis widely exists in various tissues and organs including the liver, kidney, heart, and lung, and participates in the process of fibrogenesis. Herein, we aim to elucidate the role of Tβ4-POP-Ac-SDKP axis in hepatic fibrosis, renal fibrosis, cardiac fibrosis, and pulmonary fibrosis, as well as the underlying mechanisms. Based on this, we attempted to provide novel therapeutic strategies for the regulation of tissue damage repair and anti-fibrosis therapy. The Tβ4-POP-Ac-SDKP axis exerts protective effects against organ fibrosis. It is promising that appropriate dosing regimens that rely on this axis could serve as a new therapeutic strategy for alleviating organ fibrosis in the early and late stages.
Topics: Humans; Fibrosis; Oligopeptides; Prolyl Oligopeptidases; Thymosin
PubMed: 36362069
DOI: 10.3390/ijms232113282 -
Frontiers in Bioscience (Landmark... Jan 2009Substantial evidence demonstrates a link of increased plasminogen activator inhibitor-1 (PAI-1) and glomerulosclerosis and kidney fibrosis, providing a novel therapeutic... (Review)
Review
Substantial evidence demonstrates a link of increased plasminogen activator inhibitor-1 (PAI-1) and glomerulosclerosis and kidney fibrosis, providing a novel therapeutic option for prevention and treatment of chronic kidney diseases. Several mechanisms contributing to increased PAI-1 will be addressed, including classic key profibrotic factors such as the renin-angiotensin-system (RAS) and transforming growth factor-beta (TGF-b???and novel molecules identified by proteomic analysis, such as thymosin- b4. The fibrotic sequelae caused by increased PAI-1 in kidney depend not only on its classic inhibition of tissue-type and urokinase-type plasminogen activators (tPA and uPA), but also its influence on cell migration.
Topics: Angiotensins; Animals; Chronic Disease; Disease Models, Animal; Fibrosis; Humans; Kidney Diseases; Mice; Oligopeptides; Organ Specificity; Plasminogen Activator Inhibitor 1; Renin-Angiotensin System; Thymosin; Transforming Growth Factor beta1
PubMed: 19273183
DOI: 10.2741/3361