With the aging of population and the development of social economy, the incidence of chronic wounds is increasing day by day, while the incidence of burns and trauma remains at a high level, making wound repair an increasingly concerned area in clinical practice. Thymosin β4 is a naturally occurring small molecule protein in vivo, which is widely distributed in a variety of body fluids and cells, especially in platelets. Thymosin β4 has biological activities of promoting angiogenesis, anti-inflammation, anti-apoptosis, and anti-fibrosis, and has many important functions in wound repair. Thymosin β4 has been observed to promote the healing of various wounds, such as burns, diabetic ulcers, pressure ulcers. This paper will review the molecular structure, mechanism of wound healing promotion, pharmacokinetics, and clinical application of thymosin β4, aiming to introduce its potential in wound treatment and the shortcomings of current researches.
Burns/drug therapy* ; Humans ; Pressure Ulcer ; Thymosin/therapeutic use* ; Wound Healing/physiology*

Adolescent ; Child ; Female ; Hepatitis B Antibodies ; blood ; Hepatitis B Vaccines ; immunology ; Humans ; Male ; Thymosin ; therapeutic use ; Vaccination ; Vaccines, Synthetic ; immunology

Adjuvants, Immunologic ; therapeutic use ; Adult ; Aged ; Female ; Humans ; Liver Cirrhosis ; therapy ; Male ; Middle Aged ; Peritonitis ; therapy ; Thymosin ; analogs & derivatives ; therapeutic use

OBJECTIVETo evaluate the therapeutic effect of ulinastatin combined with thymosin α1 in the treatment of severe sepsis in rats.

METHODSNormal Wistar rats were subject to cecal ligation and puncture (CLP) to establish models of severe sepsis. The rats were then randomized into 4 groups for treatment with saline (control), ulinastatin, thymosin α1, or the combination of the latter two injected through the caudal vein or subcutaneously at 6, 24, 48 and 72 h after modeling. The mortality rate was recorded daily and the rats were executed at 24, 48, 72 and 96 h after CLP to harvest the heart, liver, spleen, lung, kidney and small intestines for pathological examination. The spleen of the rats were taken for detection of apoptosis of the spleen cells.

RESULTSThe mortality rate of the septic rats in the combined treatment group was decreased significantly (P=0.0325). The control group showed the most severe organ damage, which was moderate in single drug treatment group and the mildest in combined treatment group. Obvious spleen cell apoptosis was found in the control group, and was significantly ameliorated in the combined treatment group[(47.4∓10.9)% vs (39.3∓11.4)%, P=0.0000].

CONCLUSIONCombined treatment with ulinastatin and thymosin α1 can significantly improve the prognosis and ameliorate organ damage and spleen cell apoptosis in rats with sever sepsis.

Animals ; Apoptosis ; Drug Therapy, Combination ; Glycoproteins ; therapeutic use ; Male ; Rats ; Rats, Wistar ; Sepsis ; drug therapy ; pathology ; Spleen ; cytology ; pathology ; Thymosin ; analogs & derivatives ; therapeutic use

Adjuvants, Immunologic ; therapeutic use ; Adolescent ; Adult ; Antiviral Agents ; therapeutic use ; Drug Therapy, Combination ; Female ; Hepatitis B, Chronic ; drug therapy ; Humans ; Lamivudine ; therapeutic use ; Male ; Middle Aged ; Thymosin ; analogs & derivatives ; therapeutic use

To compare the efficacy of interferon and thymosin alpha-1 combination therapy with interferon monotherapy for HBeAg positive chronic hepatitis B. The relevant randomized controlled trials were searched throughout PubMed, EBSCO, Cochrane Library, CBMdisc, VIP, WanFang since Janurary 1990. Studies were included if patients were followed up for at least 6 months after cessation of treatment. Meta-analysis was carried out with RevMan5.0 software. Subgroup analyses were used at different time of observation. Seven randomized controlled trials were included(535 patients in total). According to the results of meta-analysis, the combination therapy was remarkably more effective than monotherapy both at the end of the treatment and the follow-up in terms of HBV-DNA negative rate (54.9% vs 36.3%, OR=2.39, 95% CI=1.64-3.49, P value is less than 0.01; 58.6% vs 30.7%, OR=3.68, 95% CI=2.51-5.41, P value is less than 0.01, respectively), ALT normalization rate (74.5% vs 60.9%, OR=1.94, 95% CI=1.26-3.00, P value is less than 0.01; 74.0% vs 55.6%, OR=2.36, 95% CI=1.54-3.62, P value is less than 0.01, respectively), HBeAg loss rate (56.9% vs 36.7%, OR=2.38, 95% CI=1.61-3.51, P value is less than 0.01; 62.2% vs 33.2%, OR=3.42, 95% CI=2.31-5.06, P value is less than 0.01, respectively) , and HBeAg seroconversion rate (40.1% vs 29.0%, OR=1.65, 95% CI=1.10-2.47, P value is less than 0.05; 47.0% vs 29.5%, OR=2.13, 95% CI=1.43-3.16, P value is less than 0.01, respectively); the HBsAg loss rate of the combination therapy group was significantly higher than that of the monotherapy group only at the end of the follow-up (9.8% vs 3.7%, OR=2.92, 95% CI=1.09-7.76, P value is less than 0.05). Interferon and thymosin alpha-1 combination therapy achieves superior effect with no increase in the adverse effects as compared to interferon monotherapy for HBeAg positive chronic hepatitis B.
Antiviral Agents ; therapeutic use ; Drug Therapy, Combination ; Hepatitis B e Antigens ; blood ; Hepatitis B, Chronic ; blood ; drug therapy ; Humans ; Interferons ; therapeutic use ; Randomized Controlled Trials as Topic ; Thymosin ; analogs & derivatives ; therapeutic use ; Treatment Outcome

This study was purposed to evaluate the safety and curative effect of autologous cytokine induced killer cells (CIK) combined with low-dose IL-2 regimen containing immune enhancement of thymic peptide on elderly patients with B-cell chronic lymphocytic leukemia (B-CLL). Thymic peptide α1 was subcutaneously given as the immunoenhancement agent at a dose of 1.6 mg/d, 14 days as one cycle. Peripheral blood mononuclear cells (PBMNC) from 5 patients with B-CLL were isolated once a week to induce ex vivo CIK cells through culture in the context of interferon (IFN)-γ, interleukin (IL)-2 and anti-CD3 monoclonal antibody. The PBMNC were separated from patients before and after 14 days as one cycle of thymic peptide α1 administration. Parameters of amplification ability, effector cells quantity, lymphocyte subgroups percentage and antitumor cytotoxicity were compared before and after thymic peptide administration. The 5 patients were treated with CIK cells combined with low-dose IL-2 regimen immediately after injection of thymic peptide α1. The CIK cells plus low-dose IL-2 regimen containing thymic peptide enhancement was defined as: thymic peptide α1 1.6 mg/d was subcutaneously administered once every other day; (4 - 6) ×10(9) of CIK cells were transfused followed by IL-2 subcutaneous administration of 1 mU/d on days 1-10, 28 days as one cycle. Clinical evaluation parameters including cellular immunity function, CLL related biomarkers, disease state and infectious frequency and degree were investigated before and after CIK cells infusion puls IL-2. The results showed that the amount of amplified CIK cells, the percentage and amplification times of effector cells and antitumor cytotoxicity more significantly increased after thymic peptide α1 treatment than before its use (P < 0.05). The total 46 cycles of CIK cells infusion plus IL-2 were completed in the 5 CLL patients. No adverse reaction was observed. After treatment of CIK cells plus IL-2, the general conditions of 5 CLL patients were to different extent improved. Simultaneously, percentages of CD3(+), CD3(+)CD8(+), and CD3(+)CD56(+) cells in peripheral blood remarked by raised (P < 0.05), the serum level of β2 microglobulin was significantly declined (P < 0.05), and the frequency and degree of infection was also decreased (P < 0.05). Following CIK cells plus IL-2 therapy, the transformation of disease state from partial remission (PR) to complete remission was seen in 3 patients, from stable disease (SD) to PR in 1 patient, and from progress of disease to SD in 1 patient. It is concluded that the regimen of autologous CIK cells combined with low-dose IL-2 containing immune enhancement of thymic peptide is safety and effective for the treatment of elderly patients with B-CLL.
Aged ; Aged, 80 and over ; Cytokine-Induced Killer Cells ; immunology ; Humans ; Interleukin-2 ; administration & dosage ; therapeutic use ; Leukemia, Lymphocytic, Chronic, B-Cell ; therapy ; Male ; Thymosin ; immunology

OBJECTIVESTo evaluate if the humoral immune response of hepatitis B DNA vaccine pVAX1-S2S could be enhanced by Talpha1 and/or IFNa expression plasmid co-inoculated.

METHODSThe following mammalian expression recombinant plasmids were constructed: the plasmid pVAX1-S2S expressing hepatitis B surface antigen S2S, the plasmid pVAX1-T/I co-expressing thymosin a and IFNalpha, the plasmid pVAX1-I/S2S co-expressing IFNalpha and S2S. These plasmids were inoculated intramuscularly into several BALB/c mice groups in different combinations. In the co-immunization group 1 (pVAX1-I/S2S), each mouse was inoculated with 100 microg of pVAX1-I/S2S; in the co-immunization group 2 (pVAX1-S2S) each mouse was co-inoculated with pVAX1-S2S and 50 microg of pVAX1-TI; in the control group each mouse was inoculated with 100 microg of pVAX1-S2S. All the immunizations were boosted at 2 and 4 week intervals; then the serum samples were collected to detect the anti-HBs and anti-preS2 strengths.

RESULTS3, 5 and 8 weeks after the first inoculation, the positive rates of anti-HBs were 12.5%, 12.5%, 62.5% respectively in the co-immunization group 1 and 25%, 50%, 50% in the co-immunization group 2, while those in the control group were 0, 25%, 37.5%. The titers of anti-preS2 in co-immunization group 2 was 5 times higher than those in the other two groups.

CONCLUSIONThe data shows that Talpha1 and/or IFNalpha expression plasmid co-inoculated with pVAX1-S2S might act as an adjuvant to enhance the humoral immune response induced by pVAX1-S2S.

Adjuvants, Immunologic ; genetics ; therapeutic use ; Animals ; Female ; Hepatitis B ; immunology ; therapy ; Hepatitis B Vaccines ; immunology ; therapeutic use ; Interferon-alpha ; genetics ; immunology ; Mice ; Mice, Inbred BALB C ; Recombinant Fusion Proteins ; immunology ; Thymosin ; genetics ; immunology ; Vaccines, DNA ; immunology

OBJECTIVETo evaluate the preventive and therapeutic effect of thymosin alpha(1) on lung infections in critical patients with tracheotomy.

METHODSForty-two patients were randomly divided into treatment group and control group to receive daily subcutaneous thymosin injection at 11.6 mg and saline of 2 ml for 7 days, respectively.

RESULTSCompared with the control group, the infection rate, white blood cell count, C-reactive protein, tumor necrosis factor-alpha and interleukiu-6 were significantly lower in the treatment group.

CONCLUSIONThymosin alpha(1) can be effective for prevention and treatment of lung infections in critical patients with tracheotomy and may improve the patients' immunity and prognosis.

Adjuvants, Immunologic ; therapeutic use ; Adolescent ; Adult ; Aged ; Brain Injuries ; drug therapy ; surgery ; Cerebral Infarction ; drug therapy ; Critical Illness ; Female ; Humans ; Intensive Care Units ; Male ; Middle Aged ; Pneumonia ; prevention & control ; Thymosin ; analogs & derivatives ; therapeutic use ; Tracheotomy ; adverse effects

BACKGROUNDTradition treatment of sepsis and new therapies, including high dose corticosteroids and non-steroidal anti-inflammatory drugs, have proven unsuccessful in improving survival. This study aimed to evaluate the potential efficacy of immunomodulating therapy using Ulinastatin (UTI) plus Thymosin alpha1 (Talpha1) for improving organ function and reducing mortality in patients with severe sepsis.

METHODSA prospective study was carried out with randomized and controlled clinical analysis of 114 patients conforming to the enrollment standard. All patients had severe sepsis and received standard supportive care and antimicrobial therapy. Fifty-nine patients were also administered UTI plus Talpha1 (defined as Group A), 55 patients were given a placebo (defined as Group B). Clinical parameters were determined by evaluation with the Acute Physiology and Chronic Health Evaluation II (APACHE II), multiple organ failure (MOF) and the Glasgow Coma Scores (GCS) on entry and after therapy on the 3rd, 8th, and 28th day. By flow cytometery and ELISA lymphocyte subsets and cytokines were analyzed. Survival analysis was determined by the Kaplan-Meier method at 28, 60, and 90 days.

RESULTSBased on comparison of the two groups, patients in Group A exhibited a better performance in organ failure scores which was noticeable soon after initiation of treatment. Patients in Group A also demonstrated a better resolution of pre-existing organ failures during the observation period. After initiation of treatment, significant improvements in the CD(4)(+)/CD(8)(+) ratio, a quicker balance between proinflammatory mediators such as tumor necrosis factor alpha, interleukin 6 and anti-inflammatory cytokines including interleukin 4 and interleukin 10 were found. This was followed by cumulative survival increases of 17.3% at 28 days, 28.9% at 60 days, and 31.4% at 90 days in Group A. The reduction in mortality was accompanied by a considerably shorter stay in the ICU and a shorter length of supportive ventilation, antimicrobial and dopamine therapy.

CONCLUSIONUTI plus Talpha(1) has a beneficial role in the treatment of severe sepsis.

Adjuvants, Immunologic ; therapeutic use ; Adult ; CD4-Positive T-Lymphocytes ; immunology ; CD8-Positive T-Lymphocytes ; immunology ; Female ; Glycoproteins ; therapeutic use ; Humans ; Interleukin-10 ; metabolism ; Interleukin-6 ; metabolism ; Lymphocyte Subsets ; immunology ; Male ; Middle Aged ; Sepsis ; drug therapy ; metabolism ; mortality ; Survival Analysis ; Thymosin ; analogs & derivatives ; therapeutic use ; Treatment Outcome ; Trypsin Inhibitors ; therapeutic use ; Tumor Necrosis Factor-alpha ; metabolism