The prognostic value of thymosin β4 expression and preoperative systemic immune-inflammatory index/serum albumin level in early operable non-small cell lung cancer / 中国医师杂志

Objective:To investigate the prognostic value of thymosin β4 (TMSB4X) expression and preoperative systemic immune-inflammatory index/serum albumin (SII/ALB) level in patients with early operable non-small cell lung cancer (NSCLC).Methods:A total of 128 patients with early NSCLC admitted to Zibo Central Hospital from January 2016 to January 2021 were selected. TMSB4X and SII/ALB were detected before surgery, and they were divided into TMSB4X positive group (52 cases) and TMSB4X negative group (76 cases) according to TMSB4X expression. According to the median SII/ALB value, the patients were divided into high SII/ALB group (64 cases) and low SII/ALB group (64 cases). The relationship between TMSB4X, SII/ALB and clinical characteristics in patients with early operable NSCLC was analyzed. The survival curve was drawn by Kaplan-Meier method and the difference of progression free survival (PFS) between TMSB4X positive group and negative group, high SII/ALB group and low SII/ALB group was tested by log-rank. The influencing factors of PFS was analyzed by Cox univariate and multivariate regression.Results:There were difference in lesion site, carcinoembryonic antigen (CEA) and lymphocyte count (LY) between TMSB4X positive group and TMSB4X negative group (all P<0.05). There were significant difference in age, American Joint Committee on Cancer (AJCC) stage, ALB, cytokeratin 19 fragment (CYFRA21-1), CEA, LY, platelet count (PLT) between the high SII/ALB group and the low SII/ALB group (all P<0.05). The median PFS of TMSB4X positive group (17.11 months) was lower than that of TMSB4X negative group (26.64 months) (log rank P<0.001); The median PFS (15.82 months) in the high SII/ALB group was lower than that in the low SII/ALB group (28.24 months) (log rank P<0.0001); Cox univariate analysis showed that lesion location, AJCC stage, ALB, CYFRA21-1, CEA, LY, PLT, TMSB4X, and SII/ALB were all factors influencing PFS in early operable NSCLC patients (all P<0.05); Multivariate analysis showed that AJCC stage, LY, TMSB4X, SII/ALB were independent factors influencing PFS in early operable NSCLC patients (all P<0.05). Conclusions:The expression of TMSB4X and the preoperative level of SII/ALB can be used as prognostic indicators for patients with early operable NSCLC.

Protective effect of thymosin β4 in ocular surface diseases / 国际眼科杂志(Guoji Yanke Zazhi)

@#Thymosin is a kind of protein that is widely distributed in many tissues. It has many biological activities. Thymosin is divided into three subtypes: thymosin α, thymosin β and thymosin γ. Thymosin β4(Tβ4)is the most widely distributed in normal human body. A large number of studies have confirmed that Tβ4 has the functions of anti-inflammatory, anti-apoptosis and promoting proliferation. Ocular surface diseases are mostly related to ocular surface injury and inflammation. Therefore, promoting wound repair and healing and anti-inflammatory are the key to the treatment of ocular surface diseases. The present review mainly introduces the distribution, structure, synthesis of Tβ4 and its protective effect on ocular surface.

Role of thymosin β4 in treatment of non-alcoholic fatty liver disease in mice and its mechanism / 中华消化杂志

Objective To explore the role and mechanism of thymosin β4 (Tβ4) in the treatment of non-alcoholic fatty liver disease (NAFLD).Methods Forty male C57BL/J6 mice were divided into normal group,NAFLD group,low dose Tβ4 group and high dose Tβ4 group with 10 mice in each group.NAFLD mice model was established by feeding with high fat and high sugar diet for 16 weeks.The mice in low-dose Tβ4 group and high dose Tβ4 group were intraperitonealy injected with Tβ4 at 0.05 mg · kg-1 · d-1 and 0.20 mg · kg-1 · d-1,respectively,for eight weeks.The liver function indexes and serum tumor necrosis factor-α (TNF-α) level were detected;the pathological changes of liver tissue were observed under optical microscope and non-alcoholic fatty liver disease activity score (NAS) was evaluated.The protein expression levels of nuclear factor-κB p65 (NF-κB p65) and nuclear factor κB inhibit protein a (IκBa) at the protein level in liver tissue were measured by Western blotting method.The expression of TNF-α in liver tissue was detected by immunohistochemistry.Mean integral absorbance (MIA) was calculated.T test was performed for groups comparison.Results The levels of alanine aminotransferase (ALT),γ-glutamine transferase (GGT) and serum TNF-α levels of high dose Tβ4 group were all lower than those of NAFLD group ((28±17) U/L vs.(76±29) U/L,(61±39) U/L vs.(102±56) U/L,(144.1± 48.2) ng/L vs.(187.3±58.8) ng/L,respectively),and the differences were statistically significant (t=4.52,2.78 and 2.30,all P＜0.05).The NAS of low dose Tβ4 group and high dose Tβ4 group were both lower than that of NAFLD group (3.7±40.4,2.3±0.3 vs.4.6±0.3),and the differences were statistically significant (t=5.69 and 17.14,both P＜0.01).The relative expression level of Tβ4 protein of NAFLD group was lower than that of normal group (0.2±0.1 vs.1.4±0.6),and the difference was statistically significant (t=6.24,P＜0.01).The relative expression levels of Tβ4 and IκBa of high dose Tβ4 group were higher than those of NAFLD group (1.0±0.3,0.5±0.3 vs.0.2±0.1),and the differences were statistically significant (t=8.00 and 3.00,both P＜0.01).The relative expression level of NF-κB p65 in liver tissue of high dose Tβ4 group was lower than that of NAFLD group (0.6±0.3 vs.1.5±0.7),and the difference was statistically significant (t=3.74,P＜0.01).The MIA of high dose Tβ4 group was lower than that of NAFLD group (0.4±0.2 vs.0.7±0.3),and the difference was statistically significant (t=2.63,P＜ 0.01).Conclusion Tβ4 can effectively treat NAFLD probably through inhibiting the NF-κB pathway.

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.

Gene cloning and bioactive analysis of thymosin-β4 from skin of Nanorana yunnanensis / 中国药理学通报

Aim To investigate the gene sequences and pro-angiogenic activities of thymosin-β4 from skin of Nanorana yunnanensis. Methods Two cDNA se-quences of thymosin-β4 from Nanorana yunnanensis designated as pTβ4-1 and pTβ4-2 were obtained by PCR. The tube formation and proliferation of human umbilical vein endothelial cells ( HUVEC ) and chick-en chorioallantoic membrane ( CAM) model were used to observe the pro-angiogenic effects of synthetic pep-tides according to the reduced amino acid sequences of pTβ4-1 and pTβ4-2 in vitro and in vivo, respectively. Results The cDNA sequences of Tβ4-1 and pTβ4-2 were composed of 662 bp and 673 bp, respectively, and their deduced amino acid sequences contained 44 residues which shared highly similarity with those from human , mouse , chicken , claw frog , zebra fish , turbot and Amolops loloensis. Furthermore, the mature amino acid sequences of pTβ4-1 and pTβ4-2 had highly con-served structural regions when compared with other thy-mosin-β4 previously reported. Synthetic peptides could significantly promote proliferation and tube formation of HUVEC and angiogenesis of CAM. Conclusion There are two thymosin-β4 peptides in skins of Nanorana yunnanensis which have pro-angiogenic ac-tivities.

Protective effect of thymosin β4 on severe acute pancreatitis in rats / 中华急诊医学杂志

Objective To investigate the protective effects and mechanisms of intraperitoneal administration of thymosin β4 on severe acute pancreatitis in rats.Methods Fifty-four male Sprague-Dawley rats were randomly (random number) divided into sham operation (SO) group,severe acute pancreatitis (SAP) group and thymosin β4 (Tβ4) pretreatment group (n =18 in each group).SAP rat model was prepared by retrograde injection of 5％ sodium taurocholate into the biliopancreatic duct.Rats in Tβ4 group were treated with thymosin β4 (6 mg/kg) by intraperitoneal administration prior to SAP modeling.Six rats in each group were sacrificed at 3,6,12 hours,respectively after modeling.The serum levels of amylase,tumor necrosis factor-α (TNF-α),interleukin-1 β (IL-1 β),and interleukin-6 (IL-6)were detected,and pathological scores of the tissue of pancreas head were evaluated under light microscope.Pancreatic nuclear factor-kappa 1B (NF-κB) p65 and IκB α levels were detected by the Western blot.All data were analyzed by using the analysis of variauce or t test.Results The levels of serum amylase of SAP 3,6 and 12 hours groups were (3221 ±394) U/L,(4509 ±474) U/L and (6280 ±728) U/L,which were significantly higher than (2598±416) U/L,(3639 ±373) U/L and (4782 ±466) U/L of the Tβ4 groups (t =-2.666,-3.530,-4.245,P ＜ 0.05).The levels of serum TNF-α of the SAP 3,6 and 12 hours groups were (247.7 ± 18.5) pg/mL,(313.5 ± 17.7) pg/mL and (359.3 ±22.6) pg/mL,which were higher than (182.3 ± 13.6) pg/mL,(258.9 ± 14.9) pg/mL and (278.1 ± 16.3) pg/mL of the Tβ4 groups (t =-6.964,-5.769,-7.152,P ＜ 0.05).The levels of serum IL-1 β of the SAP 3,6 and 12 hours groups were (258.2±10.5) pg/mL,(345.1 ±22.0) pg/mL and (430.9 ±25.4) pg/mL,which were higher than (170.3 ± 12.4) pg/mL,(263.5 ± 13.3) pg/mL and (303.7 ± 16.1) pg/mL of the Tβ4 groups (t =-13.258,-7.762,-10.355,P ＜ 0.05).The levels of serum IL-6 of SAP 3,6 and 12 hours groups were (266.3 ±11.5) pg/mL,(355.0 ±24.4) pg/mL and (429.2 ±33.7) pg/ mL,which were higher than (171.1 ± 13.0) pg/mL,(234.9 ± 19.2) pg/mL and (277.2 ± 19.2) pg/ mL of the Tβ4 groups (t =-13.401,-9.474,-9.582,P ＜ 0.05).The pancreatic pathological scores of the SAP3,6 and 12 hours groups were (6.25 ±0.94),(8.83 ±0.82) and (12.08 ±1.16),which were higher than (4.17 ± 0.93),(6.33 ± 0.82) and (7.33 ± 1.25) of the Tβ4 groups (t =-3.867,-5.303,-6.823,P ＜ 0.05).The relative expression of pancreatic NF-κB p65 in SO group was (0.95 ±0.11),which was significantly lower than (2.40 ±0.17) of the SAP 12 hours group (t =-17.368,P＜ 0.05).The relative expression of pancreatic NF-κB p65 in Tβ4 group was 1.50 ± 0.10,which was significantly lower than SAP 12 hours group (t =10.917,P ＜0.05).The relative expression of pancreatic IκB α in SO group was (1.93 ±0.11),which was significantly higher than (0.78 ±0.18) of the SAP 12 hours group (t =13.260,P ＜ 0.05).The relative expression of pancreatic IκB α in Tβ4 group was (1.12±0.10),which was significantly higher than SAP 12 hours group (t =-4.112,P ＜ 0.05).Conclusions Thymosin β4 has the protective effect on SAP rat model,and the mechanism may be associated with inhibition of NF-κB signaling pathway and decreased proinflammatory cytokines.