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Pneumonia (Nathan Qld.) Sep 2023Thymosin drugs are commonly used for the treatment of viral infections due to their immunomodulatory effects. The comprehensive clinical efficacy of Thymalfasin therapy...
INTRODUCTION
Thymosin drugs are commonly used for the treatment of viral infections due to their immunomodulatory effects. The comprehensive clinical efficacy of Thymalfasin therapy for COVID-19 associated pneumonia is not yet fully researched, another issue, whether the use of thymosin drugs can reduce the rate of COVID-19 progression to severe pneumonia has not been well documented. The aim of the present study was to multi-angle evaluate the clinical efficacy of Thymalfasin therapy for COVID-19 pneumonia by retrospective review of the clinical data of 338 inpatients with common COVID-19 infection who received treatment in our hospital.
METHODS
The primary index of observation was whether progression to severe pneumonia occurred within a week after admission, and the secondary indexes were the length of hospital stay, time of negative conversion of COVID-19 antigen, the number of peripheral lymphocytes and white blood cells (WBC), and C-reactive protein (CRP) and procalcitonin (PCT) levels,and the control of pneumonia related symptoms, for example, fever, listlessness, inflammatory exudate area shown on lung CT (%).
RESULTS
The length of hospital stay of patients in Thymalfasin group was significantly shorter than that of patients in the control group (p < 0.01). The proportion of relief of pneumonia related symptoms (fever, fatigue) in the Thymalfasin therapy group was significantly higher than that in the control group, and the inflammatory exudate area shown on CT was significantly lower than that in the control group (p < 0.05). Multivariate logistic regression analysis showed that the use of Thymalfasin was an independent protective factor affecting the progression to severe pneumonia. Multifactorial Cox model analysis indicated that negative conversion of COVID-19 antigen was significantly faster in patients using Thymalfasin and younger patients.
CONCLUSION
Thymalfasin therapy has shown excellent clinical efficacy in the treatment of COVID-19 pneumonia, it can reduce inflammatory reactions, promote the relief of COVID-19 pneumonia related symptoms such as fever and fatigue, facilitate effusion absorption, and accelerate COVID-19 pneumonia recovery. Thymalfasin can prevent progression of common COVID-19 infection to severe pneumonia via multiple immunity-enhancing and anti-inflammatory protective mechanisms.
PubMed: 37743481
DOI: 10.1186/s41479-023-00116-6 -
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 -
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 -
World Journal of Virology Dec 2020Thymosin alpha 1 is a peptide naturally occurring in the thymus that has long been recognized for modifying, enhancing, and restoring immune function. Thymosin alpha 1... (Review)
Review
Thymosin alpha 1 is a peptide naturally occurring in the thymus that has long been recognized for modifying, enhancing, and restoring immune function. Thymosin alpha 1 has been utilized in the treatment of immunocompromised states and malignancies, as an enhancer of vaccine response, and as a means of curbing morbidity and mortality in sepsis and numerous infections. Studies have postulated that thymosin alpha 1 could help improve the outcome in severely ill corona virus disease 2019 patients by repairing damage caused by overactivation of lymphocytic immunity and how thymosin alpha 1 could prevent the excessive activation of T cells. In this review, we discuss key literature on the background knowledge and current clinical uses of thymosin alpha 1. Considering the known biochemical properties including antibacterial and antiviral properties, time-honored applications, and the new promising findings regarding the use of thymosin, we believe that thymosin alpha 1 deserves further investigation into its antiviral properties and possible repurposing as a treatment against severe acute respiratory syndrome coronavirus-2.
PubMed: 33362999
DOI: 10.5501/wjv.v9.i5.67 -
Cell Research Sep 2020
Topics: Adaptive Immunity; Betacoronavirus; COVID-19; Coronavirus Infections; Humans; Immunoglobulins, Intravenous; Lymphocyte Activation; Pandemics; Pneumonia, Viral; Protein Precursors; SARS-CoV-2; T-Lymphocytes; Thymalfasin; Thymosin
PubMed: 32759967
DOI: 10.1038/s41422-020-0391-9 -
The Cochrane Database of Systematic... Feb 2011Purified thymus extracts (pTE) and synthetic thymic peptides (sTP) are thought to enhance the immune system of cancer patients in order to fight the growth of tumour... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Purified thymus extracts (pTE) and synthetic thymic peptides (sTP) are thought to enhance the immune system of cancer patients in order to fight the growth of tumour cells and to resist infections due to immunosuppression induced by the disease and antineoplastic therapy.
OBJECTIVES
To evaluate the effectiveness of pTE and sTP for the management of cancer.
SEARCH STRATEGY
We searched CENTRAL (The Cochrane Library 2010, Issue 3), MEDLINE, EMBASE, AMED, BIOETHICSLINE, BIOSIS, CATLINE, CISCOM, HEALTHSTAR, HTA, SOMED and LILACS (to February 2010).
SELECTION CRITERIA
Randomised trials of pTE or sTP in addition to chemotherapy or radiotherapy, or both, compared to the same regimen with placebo or no additional treatment in adult cancer patients.
DATA COLLECTION AND ANALYSIS
Two authors independently extracted data from published trials. We derived odds ratios (OR) from overall survival (OS) and disease-free survival (DFS) rates, tumour response (TR) rates, and rates of adverse effects (AE) related to antineoplastic treatments. We used a random-effects model for meta-analysis.
MAIN RESULTS
We identified 26 trials (2736 patients). Twenty trials investigated pTE (thymostimulin or thymosin fraction 5) and six trials investigated sTP (thymopentin or thymosin α(1)). Twenty-one trials reported results for OS, six for DFS, 14 for TR, nine for AE and 10 for safety of pTE and sTP. Addition of pTE conferred no benefit on OS (RR 1.00, 95% CI 0.79 to 1.25); DFS (RR 0.97, 95% CI 0.82 to 1.16); or TR (RR 1.07, 95% CI 0.92 to 1.25). Heterogeneity was moderate to high for all these outcomes. For thymosin α(1) the pooled RR for OS was 1.21 (95% CI 0.94 to 1.56, P = 0.14), with low heterogeneity; and 3.37 (95% CI 0.66 to 17.30, P = 0.15) for DFS, with moderate heterogeneity. The pTE reduced the risk of severe infectious complications (RR 0.54, 95% CI 0.38 to 0.78, P = 0.0008; I² = 0%). The RR for severe neutropenia in patients treated with thymostimulin was 0.55 (95% CI 0.25 to 1.23, P = 0.15). Tolerability of pTE and sTP was good. Most of the trials had at least a moderate risk of bias.
AUTHORS' CONCLUSIONS
Overall, we found neither evidence that the addition of pTE to antineoplastic treatment reduced the risk of death or disease progression nor that it improved the rate of tumour responses to antineoplastic treatment. For thymosin α(1), there was a trend for a reduced risk of dying and of improved DFS. There was preliminary evidence that pTE lowered the risk of severe infectious complications in patients undergoing chemotherapy or radiotherapy.
Topics: Adjuvants, Immunologic; Adult; Disease-Free Survival; Female; Humans; Immune System; Immunocompromised Host; Male; Neoplasms; Peptides; Thymalfasin; Thymopentin; Thymosin; Thymus Extracts; Thymus Gland
PubMed: 21328265
DOI: 10.1002/14651858.CD003993.pub3 -
Journal For Immunotherapy of Cancer Jun 2023Advanced or metastatic prostate cancer (PCa) is still an incurable malignancy with high lethality and a poor prognosis. Despite the remarkable success of immunotherapy...
BACKGROUND
Advanced or metastatic prostate cancer (PCa) is still an incurable malignancy with high lethality and a poor prognosis. Despite the remarkable success of immunotherapy against many types of cancer, most patients with PCa receive minimal benefit from current immunotherapeutic strategies, because PCa is an immune cold tumor with scarce T-cell infiltration in the tumor microenvironment. The aim of this study was to develop an effective immunotherapeutic approach for immune cold PCa tumors.
METHODS
The therapeutic efficacy of androgen deprivation therapy (ADT) and zoledronic acid (ZA) plus thymosin α1 (Tα1) therapy was analyzed retrospectively in patients with advanced or metastatic PCa. The effects and mechanisms by which ZA and Tα1 regulated the immune functions of PCa cells and immune cells were evaluated by a PCa allograft mouse model, flow cytometric analysis, immunohistochemical and immunofluorescence staining assays, and PCR, ELISA, and Western blot analyses.
RESULTS
In this study, clinical retrospective analysis revealed that ADT combined with ZA plus Tα1 improved the therapeutic outcomes of patients with PCa, which might be associated with an enhanced frequency of T cells. ZA and Tα1 treatment synergistically inhibited the growth of androgen-independent PCa allograft tumors, with increased infiltration of tumor-specific cytotoxic CD8 T cells and enhanced tumor inflammation. Functionally, ZA and Tα1 treatment relieved immunosuppression in PCa cells, stimulated pro-inflammatory macrophages, and enhanced the cytotoxic function of T cells. Mechanistically, ZA plus Tα1 therapy blocked the MyD88/NF-κB pathway in PCa cells but activated this signaling in macrophages and T cells, altering the tumor immune landscape to suppress PCa progression.
CONCLUSIONS
These findings uncover a previously undefined role for ZA and Tα1 in inhibiting the disease progression of immune cold PCa tumors by enhancing antitumor immunity and pave the way for the application of ZA plus Tα1 therapy as an immunotherapeutic strategy for treating patients with immunologically unresponsive PCa.
Topics: Humans; Male; Animals; Mice; Zoledronic Acid; Thymalfasin; Prostatic Neoplasms; Retrospective Studies; T-Lymphocytes, Cytotoxic; CD8-Positive T-Lymphocytes; Androgen Antagonists; Androgens; Inflammation; Tumor Microenvironment
PubMed: 37295817
DOI: 10.1136/jitc-2022-006381 -
International Journal of Molecular... Feb 2021Cystic fibrosis (CF) is an inherited disorder caused by mutations in the gene encoding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein, an... (Review)
Review
Cystic fibrosis (CF) is an inherited disorder caused by mutations in the gene encoding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein, an ATP-gated chloride channel expressed on the apical surface of airway epithelial cells. CFTR absence/dysfunction results in defective ion transport and subsequent airway surface liquid dehydration that severely compromise the airway microenvironment. Noxious agents and pathogens are entrapped inside the abnormally thick mucus layer and establish a highly inflammatory environment, ultimately leading to lung damage. Since chronic airway inflammation plays a crucial role in CF pathophysiology, several studies have investigated the mechanisms responsible for the altered inflammatory/immune response that, in turn, exacerbates the epithelial dysfunction and infection susceptibility in CF patients. In this review, we address the evidence for a critical role of dysfunctional inflammation in lung damage in CF and discuss current therapeutic approaches targeting this condition, as well as potential new treatments that have been developed recently. Traditional therapeutic strategies have shown several limitations and limited clinical benefits. Therefore, many efforts have been made to develop alternative treatments and novel therapeutic approaches, and recent findings have identified new molecules as potential anti-inflammatory agents that may exert beneficial effects in CF patients. Furthermore, the potential anti-inflammatory properties of CFTR modulators, a class of drugs that directly target the molecular defect of CF, also will be critically reviewed. Finally, we also will discuss the possible impact of SARS-CoV-2 infection on CF patients, with a major focus on the consequences that the viral infection could have on the persistent inflammation in these patients.
Topics: Animals; Anti-Bacterial Agents; Anti-Inflammatory Agents; Azithromycin; COVID-19; Cannabinoids; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Eicosanoids; Humans; Inflammation; Protein Kinase Inhibitors; Roscovitine; Signal Transduction; Thymalfasin; COVID-19 Drug Treatment
PubMed: 33669352
DOI: 10.3390/ijms22041952 -
BMJ Open Mar 2024The PRaG regimen, which consists of hypofractionated radiotherapy combined with a programmed cell death-1/programmed cell death ligand-1 (PD-1/PD-L1) inhibitor and...
Evaluation of the efficacy and safety of a precise thymalfasin-regulated PRaG regimen for advanced refractory solid tumours: protocol for the open-label, prospective, multicentre study (PRaG5.0 study).
INTRODUCTION
The PRaG regimen, which consists of hypofractionated radiotherapy combined with a programmed cell death-1/programmed cell death ligand-1 (PD-1/PD-L1) inhibitor and granulocyte-macrophage colony stimulating factor (GM-CSF), has been demonstrated to have a survival benefit in patients with advanced solid tumours who have failed at least two lines of treatment. Nonetheless, lymphopenia poses an impediment to the enduring efficacy of PD-1/PD-L1 inhibitor therapy. Adequate lymphocyte reserves are essential for the efficacy of immunotherapy. Coupling the PRaG regimen with immunomodulatory agents that augment the number and functionality of lymphocytes may yield further survival benefits in this cohort of patients.
OBJECTIVE
The aim of this study is to investigate the effectiveness and safety of a meticulously thymalfasin-controlled PRaG regimen in patients with advanced and chemotherapy-resistant solid tumours.
METHODS AND ANALYSIS
The study has a prospective, single-arm, open-label, multicentre design and aims to recruit up to 60 patients with histologically confirmed advanced solid tumours that have relapsed or metastasised. All eligible patients will receive a minimum of two cycles of the PRaG regimen comprising thymalfasin followed by maintenance treatment with a PD-1/PD-L1 inhibitor and thymalfasin for 1 year or until disease progression. Patients will be monitored according to the predetermined protocol for a year or until disease progression after initiation of radiotherapy.
ETHICS AND DISSEMINATION
The study protocol was approved by the Ethics Committee of the Second Affiliated Hospital of Soochow University, on 25 November 2022 (JD-LK-2022-151-01) and all other participating hospitals. Findings will be disseminated through national and international conferences. We also plan to publish our findings in high-impact peer-reviewed journal.
TRIAL REGISTRATION NUMBER
NCT05790447.
Topics: Humans; Thymalfasin; Prospective Studies; Immune Checkpoint Inhibitors; Programmed Cell Death 1 Receptor; Neoplasms; Disease Progression; Antineoplastic Combined Chemotherapy Protocols; Multicenter Studies as Topic
PubMed: 38458816
DOI: 10.1136/bmjopen-2023-075642 -
The American Journal of Emergency... Mar 2022