Research advances on thymosin β4 in promoting wound healing / 中华烧伤杂志

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.

Perspectivas de tratamiento para COVID-19 (en progreso) / Treatment prospects for COVID-19 (in progress)

CONTEXTO: Debido a la contingencia por COVID-19 provocada por el nuevo coronavirus, SARS-CoV-2, en la actualidad hay una intensa investigación de alternativas terapéuticas que sean seguras y eficaces. (Hay registrados 2208 protocolos de estudios en ClinicalTrials.gov1). Con el propósito de conocer el panorama terapéutico actual contra COVID-19, se realizó una búsqueda exhaustiva de las alternativas que han demostrado cierta eficacia en esta infección, concluyendo que los estudios que se han realizado tienen limitaciones metodológicas. Se trata de estudios no controlados, con alta probabilidad de sesgos que comprometen la validez interna y externa, consideran evidencia indirecta o la experiencia de expertos ante esa emergencia sanitaria, por lo que toda recomendación derivada de estos documentos debe de tomarse con extrema cautela. El uso de esas alternativas debe considerar los riesgos y los beneficios en casos individuales, en una decisión compartida entre médicos, pacientes y familiares ya que la mayoría de la evidencia se considera de baja o muy baja calidad. A la fecha no existe tratamiento específico en contra de este virus. BÚSQUEDA REALIZADA: Inmunoglobulinas intravenosas: Las inmunoglobulinas intravenosas (IgIV) es un grupo de IgG obtenido de donantes sanos, expuestos a enfermedades infecciosas endémicas, vacunas y microorganismos ubicuos que participan en la producción de anticuerpos IgG contra diferentes microorganismos y sus productos. El uso de inmunoglobulina intravenosa se ha

Engineered M13 Nanofiber Accelerates Ischemic Neovascularization by Enhancing Endothelial Progenitor Cells

Dysfunction or loss of blood vessel causes several ischemic diseases. Although endothelial progenitor cells (EPCs) are a promising source for cell-based therapy, ischemia-induced pathophysiological condition limits the recovery rate by causing drastic cell death. To overcome this issue, we attempted to develop a cell-targeted peptide delivery and priming system to enhance EPCbased neovascularization using an engineered M13 bacteriophage harboring nanofibrous tubes displaying ∼ 2700 multiple functional motifs. The M13 nanofiber was modified by displaying RGD, which is an integrin-docking peptide, on the minor coat protein, and bymutilayering SDKPmotifs,which are the key active sites for thymosin b4, on themajor coat protein. The engineered M13 nanofiber dramatically enhanced ischemic neovascularization by activating intracellular and extracellular processes such as proliferation, migration, and tube formation in the EPCs. Furthermore, transplantation of the primed EPCs with the M13 nanofiber harboring RGD and SDKP facilitated functional recovery and neovascularization in a murine hindlimb ischemia model. Overall, this study demonstrates the effectiveness of theM13 nanofiber-based novel peptide deliveryandprimingstrategy inpromotingEPC bioactivity and neovessel regeneration. To our knowledge, this is first report onM13 nanofibers harboring dual functional motifs, the use of which might be a novel strategy for stem and progenitor cell therapy against cardiovascular ischemic diseases.

Increased Expression of Thymosin β₄ Is Independently Correlated with Hypoxia Inducible Factor-1α (HIF-1α) and Worse Clinical Outcome in Human Colorectal Cancer

BACKGROUND: Thymosin β₄ is a multi-functional hormone-like polypeptide, being involved in cell migration, angiogenesis, and tumor metastasis. This study was undertaken to clarify the clinicopathologic implications of thymosin β₄ expression in human colorectal cancers (CRCs). METHODS: We investigated tissue sections from 143 patients with CRC by immunohistochemistry. In addition, we evaluated the expression patterns and the clinico-pathological significance of thymosin β₄ expression in association with hypoxia inducible factor-1α (HIF-1α) expression in the CRC series. RESULTS: High expression of thymosin β₄ was significantly correlated with lymphovascular invasion, invasion depth, regional lymph node metastasis, distant metastasis, and TNM stage. Patients with high expression of thymosin β₄ showed poor recurrence-free survival (p = .001) and poor overall survival (p = .005) on multivariate analysis. We also found that thymosin β4 and HIF-1α were overexpressed and that thymosin β₄ expression increased in parallel with HIF-1α expression in CRC. CONCLUSIONS: A high expression level of thymosin β₄ indicates poor clinical outcomes and may be a useful prognostic factor in CRC. Thymosin β₄ is functionally related with HIF-1α and may be a potentially valuable biomarker and possible therapeutic target for CRC.

Thymosin β4 impeded murine stem cell proliferation with an intact cardiovascular differentiation / 华中科技大学学报（医学）（英德文版）

Thymosin β4 (Tβ4) is a key factor in cardiac development, growth, disease, epicardial integrity, blood vessel formation and has cardio-protective properties. However, its role in murine embryonic stem cells (mESCs) proliferation and cardiovascular differentiation remains unclear. Thus we aimed to elucidate the influence of Tβ4 on mESCs. Target genes during mESCs proliferation and differentiation were detected by real-time PCR or Western blotting, and patch clamp was applied to characterize the mESCs-derived cardiomyocytes. It was found that Tβ4 decreased mESCs proliferation in a partial dose-dependent manner and the expression of cell cycle regulatory genes c-myc, c-fos and c-jun. However, mESCs self-renewal markers Oct4 and Nanog were elevated, indicating the maintenance of self-renewal ability in these mESCs. Phosphorylation of STAT3 and Akt was inhibited by Tβ4 while the expression of RAS and phosphorylation of ERK were enhanced. No significant difference was found in BMP2/BMP4 or their downstream protein smad. Wnt3 and Wnt11 were remarkably decreased by Tβ4 with upregulation of Tcf3 and constant β-catenin. Under mESCs differentiation, Tβ4 treatment did not change the expression of cardiovascular cell markers α-MHC, PECAM, and α-SMA. Neither the electrophysiological properties of mESCs-derived cardiomyocytes nor the hormonal regulation by Iso/Cch was affected by Tβ4. In conclusion, Tβ4 suppressed mESCs proliferation by affecting the activity of STAT3, Akt, ERK and Wnt pathways. However, Tβ4 did not influence the in vitro cardiovascular differentiation.

Effect of Acupuncture on Prognosis and Immune Function of Sepsis Patients / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To study the effect of acupuncture on the immune function of sepsis patients.</p><p><b>METHODS</b>Ninety sepsis patients were assigned to the control group, the thymosin a1 group, and the acupuncture treatment group according to random digit table, 30 patients in each group. Patients in the control group were treated according to the guideline of Surviving Sepsis Campaign (SSC). Patients in the control group received routine treatment. Those in the thymosin alpha1 group additionally received subdermal injection of thymosin alpha1 (1.6 mg), once per day for 6 successive days. Needling at related points such as Zusanli (ST36), Yanglingquan (GB34), Neiguan (PC6), Guanyuan (RN4), and so on, was performed in patients of the acupuncture treatment group, once per day for 6 successive days. T cell subgroups (CD3+, CD4+, CD8+, CD4+ /CD8+) and immunoglobulin levels (IgG, IgA, IgM) were detected. The length of ICU hospital stay, hospital readmission rate, and 28-day mortality were compared among the three groups.</p><p><b>RESULTS</b>After six days of treatment, CD3+, CD4+, CD8+, IgG, IgA, IgM, and CD4+ /CD8+ ratio of three groups were all significantly increased (P < 0.01). Of them, CD3+, CD4+, CD8+, IgG, IgA, and IgM increased more significantly in the thymosin alpha1 group and the acupuncture treatment group (P < 0.01). Compared with the control group, the ICU hospitalization length was significantly shortened, the hospital readmission rate and the 28-day mortality were lower in the thymosin alpha1 group and the acupuncture treatment group (P < 0.05, P < 0.01). There was no statistical difference in each index between the thymosin alpha1 group and the acupuncture treatment group (P > 0.05).</p><p><b>CONCLUSION</b>Acupuncture could adjust the immune function of sepsis patients, improve their immunological indicators and prognoses.</p>

Thymosin Beta-4, Actin-Sequestering Protein Regulates Vascular Endothelial Growth Factor Expression via Hypoxia-Inducible Nitric Oxide Production in HeLa Cervical Cancer Cells

Vascular endothelial growth factor (VEGF) is an important regulator of neovascularization. Hypoxia inducible nitric oxide (NO) enhanced the expression of VEGF and thymosin beta-4 (Tbeta4), actin sequestering protein. Here, we investigated whether NO-mediated VEGF expression could be regulated by Tbeta4 expression in HeLa cervical cancer cells. Hypoxia inducible NO production and VEGF expression were reduced by small interference (si) RNA of Tbeta4. Hypoxia response element (HRE)-luciferase activity and VEGF expression were increased by the treatment with N-(beta-D-Glucopyranosyl)-N2-acetyl-S-nitroso-D, L-penicillaminamide (SNAP-1), to generate NO, which was inhibited by the inhibition of Tbeta4 expression with Tbeta4-siRNA. In hypoxic condition, HRE-luciferase activity and VEGF expression were inhibited by the treatment with N(G)-monomethyl-L-arginine (L-NMMA), an inhibitor to nitric oxide synthase (NOS), which is accompanied with a decrease in Tbeta4 expression. VEGF expression inhibited by L-NMMA treatment was restored by the transfection with pCMV-Tbeta4 plasmids for Tbeta4 overexpression. Taken together, these results suggest that Tbeta4 could be a regulator for the expression of VEGF via the maintenance of NOS activity.

Thymosin Beta-4 Recombinant Adeno-associated Virus Enhances Human Nucleus Pulposus Cell Proliferation and Reduces Cell Apoptosis and Senescence / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Thymosin beta-4 (TB-4) is considered key roles in tissue development, maintenance and pathological processes. The study aimed to prove TB-4 positive biological function on nucleus pulposus (NP) cell apoptosis and slowing the process of cell aging while increasing the cell proliferation.</p><p><b>METHODS</b>TB-4 recombinant adeno-associated virus (AAV) was constructed and induced to human NP cells. Cell of same group were cultured without gene modification as controlled group. Proliferation capacity and cell apoptosis were observed during 6 passages of the cells. Morphology and expression of the TB-4 gene were documented as parameter of cell activity during cell passage.</p><p><b>RESULTS</b>NP cells with TB-4 transfection has normal TB-4 expression and exocytosis. NP cells with TB-4 transfection performed significantly higher cell activity than that at the control group in each generation. TB-4 recombinant AAV-transfected human NP cells also show slower cell aging, lower cell apoptosis and higher cell proliferation than control group.</p><p><b>CONCLUSIONS</b>TB-4 can prevent NP cell apoptosis, slow NP cell aging and promote NP cell proliferation. AAV transfection technique was able to highly and stably express TB-4 in human NP cells, which may provide a new pathway for innovation in the treatment of intervertebral disc degenerative diseases.</p>

Angiogenic effects of recombinant thymosin beta4 in a mouse hindlimb ischemia model / 동물의과학연구지

Recombinant thymosin beta4 (rTbeta4) has been reported to migrate and promote vascularization, wound-healing, and hair growth in a mouse hindlimb ischemia model of peripheral vascular disease. C57BL/6 mice (11-weeks-old) were anesthetized and an ischemic model was made by cutting the right aorta femoralis. The ischemic group was intraperitoneally administered with saline (300 microL/mouse) and the muscular administration group received rTbeta4 (150 microg in 300 microL of saline) or rTbeta4 (150 microg in 300 microL saline) to the abdominal cavity at 3-day intervals for 21 days. Myoatrophy of the ischemic group was observed compared to the normal control group. Generation of adjacent vessels was carried out in the rTbeta4 administration group compared to the ischemic group. The biopsy results showed significant fibrosis around the muscular undersurface and perimysium in the musculus quadriceps femoris of the ischemic group, whereas partial fibrosis was observed in the perimysium and endomysium in the rTbeta4 administration group. Immunostaining indicated that expression levels of hypoxiainducible factor-1alpha (HIF-1alpha), vascular endothelial growth factor-1 (VEGF-1), and endothelial nitric oxide synthase (eNOS) in the rTbeta4 group were higher than those of the ischemic group. Western blotting showed that expression levels of HIF-1alpha, VEGF-1, and eNOS in the rTbeta4 group were higher than those of the ischemic group. In conclusion, rTbeta4 increases expression levels of HIF-1alpha, VEGF-1, and eNOS, resulting in angiogenesis.

Thymosin ß4 expression in colorectal polyps and adenomas

OBJECTIVE: Thymosin beta 4 (Tβ4) is a ubiquitous peptide that plays pivotal roles in the cytoskeletal system and in cell differentiation. Recently, a role for Tβ4 has been proposed in experimental and human carcinogenesis, including gastrointestinal cancer. This study was aimed at evaluating the relationship between Tβ4 immunoreactivity and the initial steps of carcinogenesis. METHODS: In total, 60 intestinal biopsies, including 10 hyperplastic polyps, 10 sessile serrated adenomas/polyps, 15 colorectal adenomas with low-grade dysplasia, 15 adenomas with high-grade dysplasia, 15 adenocarcinomas and 10 samples of normal colon mucosa, were analyzed for Tβ4 expression by immunohistochemistry. RESULTS: Weak cytoplasmic reactivity for Tβ4 was detected in the normal colon mucosa. No reactivity for Tβ4 was found in hyperplastic and sessile serrated polyps/adenomas. Tβ4 expression was observed in 10/15 colorectal adenocarcinomas. In adenomas with low-grade dysplasia, Tβ4 immunoreactivity was mainly detected in dysplastic glands but was absent in hyperplastic glands. Tβ4 immunoreactivity was characterized by spot-like perinuclear staining. In high-grade dysplastic polyps, immunostaining for Tβ4 appeared diffuse throughout the entire cytoplasm of dysplastic cells. Spot-like perinuclear reactivity was detected in adenocarcinoma tumor cells. CONCLUSIONS: Our study shows for the first time that Tβ4 is expressed during different steps of colon carcinogenesis. The shift of Tβ4 immunolocalization from low-grade to high-grade dysplastic glands suggests a role for Tβ4 in colorectal carcinogenesis. However, the real meaning of Tβ4 reactivity in dysplastic intestinal epithelium remains unknown. .

Effect of thymosin alpha-1 on subpopulations of Th1, Th2, Th17, and regulatory T cells (Tregs) in vitro

Thymosin alpha 1 (Tα1) has been shown to have beneficial effects on numerous immune system parameters, but little is known about the effects of Tα1 on patients with gastric carcinoma. The objective of this study was to determine the effect of Tα1 on subpopulations of Th1, Th2, Th17, and regulatory T cells (Tregs) in vitro, and to evaluate its efficacy as an immunoregulatory factor in patients with gastric carcinoma. We compared the effect of Tα1 on the frequency of CD4+ and CD8+ T cells, especially the CD4+CD25+Foxp3+ Tregs in peripheral blood mononuclear cells (PBMCs) from gastric carcinoma patients (N = 35) and healthy donors (N = 22). We also analyzed the changes in the proliferation of PBMCs in response to treatment with Tα1, and examined the production of Th1, Th2, and Th17 cytokines by PBMCs and tumor-infiltrating lymphocytes. The treatment of PBMCs from gastric cancer patients, with Tα1 (50 µg/mL) alone increased the percentage of CD4+CD25+Foxp3+ (suppressive antitumor-specific Tregs) from 1.68 ± 0.697 to 2.19 ± 0.795 percent (P < 0.05). Our results indicate that Tα1 increases the percentage of Tregs and IL-1β, TNF-α, and IL-6 in vitro.

Ulinastatin combined with thymosin α1 for treatment of severe sepsis: a histopathological observation in rats / 南方医科大学学报

<p><b>OBJECTIVE</b>To evaluate the therapeutic effect of ulinastatin combined with thymosin α1 in the treatment of severe sepsis in rats.</p><p><b>METHODS</b>Normal 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.</p><p><b>RESULTS</b>The 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].</p><p><b>CONCLUSION</b>Combined treatment with ulinastatin and thymosin α1 can significantly improve the prognosis and ameliorate organ damage and spleen cell apoptosis in rats with sever sepsis.</p>

Short-term curative efficacy of autologous cytokine induced killer cells combined with low-dose IL-2 regimen containing immune enhancement by thymic peptide in elderly patients with B-cell chronic lymphocytic leukemia / 中国实验血液学杂志

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.

overview of purification, biological activities and therapeutic applications of thymosin alpha

Thymosin alpha 1 [T alpha 1] is 28 amino acid residues peptide. Thymic epithelial cells produce acetylated N-terminal T alpha 1 that has powerful immunostimulatory and antitumor activites. Inside the body T alpha 1 effects endocrine, immune and central nervous system. T alpha 1 can be purified by using fractionation procedures from thymus. Many recombinant DNA techniques are being used for the production of T alpha 1. In addition T alpha 1 is being expressed as fusion proteins with other therapeutically important proteins. For the high-throughput production of T alpha 1, different expression systems are being used such as E.coli and yeast. T alpha 1 has unique antitumor and immunoregulatory properties and also have capacity to protect cells from oxidative damage. T alpha 1 has many therapeutic applications specifically against many infectious diseases [hepatitis B and C, AIDS, SARS etc.] and cancer

Treatment with interferon and thymosin alpha-1 versus interferon monotherapy for HBeAg positive chronic hepatitis B: a meta-analysis / 中华肝脏病杂志

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.

An experimental study on the regulation of bone marrow-derived mesenchymal stem cells through indoleamine 2,3-dioxygenase signaling pathway by thymosin α1 for improving the immunosuppression mediated by T cell / 中华儿科杂志

<p><b>OBJECTIVE</b>To study the regulatory effect of thymosin α1 (Tα1) on immunosuppression of bone marrow mesenchymal stem cells (MSCs) from children with aplastic anemia (AA) through Toll-like receptor 9(TLR9)and indoleamine 2,3-dioxygenase (IDO) signaling pathway.</p><p><b>METHOD</b>Bone marrow T cell subsets from children with AA and normal individuals were measured by using flow cytometry. Expressions of TLR9/IDO mRNA of MSCs cocultured with Tα1 were determined by reverse-transcription PCR (RT-PCR). Inhibition of PHA-activated T cell proliferation and activation by MSCs cocultured with Tα1 was detected by using MTT assay and flow cytometry.</p><p><b>RESULT</b>CD4(+)/CD8(+) ratio (0.64 ± 0.02) in children with AA was significantly lower than that in normal individuals (1.42 ± 0.05); but CD8(+)/CD38(+) ratio (0.92 ± 0.04) was significantly higher than that in normal individuals (0.65 ± 0.05). AA MSCs obviously expressed TLR9, but not IDO; AA MSCs treated with Tα1 downregulated TLR9 expression but upregulated IDO expression in concentration- and time-dependent manners. The inhibition of AA MSCs on T cell proliferation (21.38% ± 12.34%) was lower than that in normal individuals (62.72% ± 17.79%, P < 0.05), while AA MSCs treated with Tα1 for 18 h exhibited a stronger inhibition (42.83% ± 16.54%, P < 0.05).</p><p><b>CONCLUSION</b>The immunosuppression mediated by MSCs could be improved by Tα1 through upregulation of IDO expression via TLR9-dependent signaling pathway. This research provides a new idea for targeted immunomodulatory therapy with bone marrow MSCs from children with AA.</p>

Regulatory effect of thymosin α1 on expression of tlr9/ido mRNA in bone marrow mesenchymal stem cells from children with aplastic anemia / 中国实验血液学杂志

The purpose of this study was to explore the regulatory effect of thymosin α1 (Tα1) on expression of TOLL-like receptor 9 (TLR9)/indoleamine2, 3-dioxygenase (ido) mRNA in bone marrow mesenchymal stem cells (MSC) from children with aplastic anemia (AA). Culture system of bone marrow MSC from AA children and normal children in vitro was established, and the effects of Tα1 on expressions of tlr9 mRNA and ido mRNA of MSC from AA children and normal children were determined by RT-PCR. The results showed that the bone marrow MSC from normal children did not express tlr9 and ido mRNA. Bone marrow MSC from children with AA obviously expressed tlr9 mRNA , but did not express ido mRNA; AA children's MSC treated with Tα1 for 18 hours markedly down-regulated tlr9 mRNA expression, but up-regulated ido mRNA expression in the concentration- and time-dependent ways. It is concluded that Tα1 can up-regulate the expression of ido mRNA in bone marrow MSC from children with AA.

Effects of immune modulation therapy on cardiac function in aged patients with chronic heart failure / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the effect of immune modulation therapy on cardiac function and lymphocyte subsets in aged patients with chronic heart failure (CHF).</p><p><b>METHODS</b>CHF (NYHA classification: II-IV) patients older than 60 years were randomly divided into two groups: CHF intervention group received regular therapy and thymopetide (2 mg/day i.m. for 75 days, n = 48), CHF control group received regular therapy (n = 48), 45 healthy individuals older than 60 years served as normal control. Left ventricular ejection faction of (LVEF), inner diameter of left ventricular end-diastole (LVEDD), inner diameter of left ventricular end-systole (LVESD), lymphocyte subsets, plasma high sensitive C-reactive protein (hsCRP), plasma brain natrium peptide (BNP) and 6 minutes walking distance (6MWT) were measured at before therapy, after the first course (15 days) of treatment and after the third course of treatment (75 days).</p><p><b>RESULTS</b>(1) Before therapy, the levels of BNP, hsCRP, CD8 T cells, LVEDD and LVESD were significantly higher and the levels of CD3, CD4, CD19 T cells, NK, CD4/CD8 ratio, LVEF and 6MWT were significantly lower in CHF patients compared to compared normal controls (all P < 0.05). These parameters were similar between CHF intervention group and CHF control group. (2) At 15 days, the levels of CD3, CD4, CD19 T cells and NK were significantly increased (P < 0.05 or P < 0.01) while the level of CD8, BNP and hsCRP were significantly decreased (P < 0.05 or P < 0.01) in CHF intervention group compared with CHF control group. (3) At 75 days, the levels of CD3, CD4, CD19 T cells, NK, CD4/CD8, LVEF and 6MWT were significantly increased (P < 0.05 or P < 0.01) while the levels of CD8, BNP, hsCRP and Minnesota Living with Heart Failure Questionnaire (MLHFQ) were significantly decreased (P < 0.05 or P < 0.01) in CHF intervention group compared with CHF control group.</p><p><b>CONCLUSION</b>Thymopetide, an immune modulating agent, might regulate the quantity and proportion of lymphocyte subsets and improve cardiac function in aged patients with CHF, indicating that immune modulation therapy might be a new treatment strategy for aged CHF patients.</p>

Treatment of patients with severe sepsis using ulinastatin and thymosin alpha1: a prospective, randomized, controlled pilot study / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Tradition 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.</p><p><b>METHODS</b>A 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.</p><p><b>RESULTS</b>Based 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.</p><p><b>CONCLUSION</b>UTI plus Talpha(1) has a beneficial role in the treatment of severe sepsis.</p>

High expression of thymosin alpha 1 by injecting recombinant PVX vector into the tomato fruit / 生物工程学报

For expression of foreign genes in plant, plant virus vector provides many advantages, such as high expression level, short expression period and wider plant hosts. In the present study, we report the expression of thymosin alpha 1 (Talpha1) in tomato fruits by potato virus X (PVX) vector. Talpha1 gene fragment from plasmid pGEM-T containing Talpha1 gene was cloned into plant virus vector pGR107 and the resulting pGR107-Talpha1 plasmid was confirmed by digestion with Sal I and Cla I. To express the Talpha1 protein, Agrobacterium tumefaciens GV3101 transformed with pGR107-Talpha1 was directly injected into tomato fruits through the fruit stylar apex at different developmental stages. The ELISA results showed that Talpha1 protein was expressed successfully in fruits, and the highest expression level was obtained from 2.5-3 week-old tomato fruits inoculated by bacterium at 1.0 OD600 density.