Thymosin beta-4 prenatal administration improves fetal development and halts side effects due to preterm delivery.

OBJECTIVE: Thymosin beta 4 (TB4) is the most abundant member of the beta-thymosin family in humans. The main physiological role of TB4 is the regulation of actin polymerization. TB4 is also involved in angiogenesis, cell survival, cell migration and fetal development. The aim of this study was to evaluate the activity of TB4 as a fetal growth promoter when administered during pregnancy. MATERIALS AND METHODS: Our protocols have been carried out in full conformity with the rules and guidelines expected for this kind of trial. 10 pregnant mice received the same injection regimen. Only 6 of these 10 are part of this experiment because they were pregnant. At 10:00 a.m. on day E14 and E17 of gestation mice were weighed and treated with an intraperitoneal injection of TB4 (Regene RX, Rockville, MD, USA; 6 mg/kg in PBS). RESULTS: The mothers treated with TB4 for two days precisely E14 and E17, showed a higher cranio-caudal length when compared to control newborns. At histology, maternal TB4 treatment was associated with more advanced development of lungs, heart, kidney, cerebral cortex and notochord. CONCLUSIONS: Our study shows that TB4 administration during gestation may act as a powerful fetal growth promoter, by accelerating the development of newborn organs and tissues.

Therapeutic effect of Xuebijing combined with thymosin on hemorrhagic fever with renal syndrome: A protocol of systematic review and meta-analysis.

BACKGROUND: The goal of this study is to assess the therapeutic effect of Xuebijing combined with thymosin (XBJ-T) for the treatment of patients with hemorrhagic fever with renal syndrome (HFRS). METHODS: We will search the electronic databases of Cochrane Library, PUBMED, EMBASE, PsycINFO, Scopus, Opengrey, Cumulative Index to Nursing and Allied Health Literature, Web of Science, Google scholar, Allied and Complementary Medicine Database, and Chinese Biomedical Literature Database from inception to the present. No language and publication status will be employed in this study. Based on the predefined eligibility criteria, selection of study and data extraction will be performed by 2 researchers independently. Study quality will be assessed using Cochrane risk of bias tool. We will apply RevMan 5.3 software to pool and analyze the extracted data. RESULTS: This study will assess the therapeutic effect of XBJ-T for the treatment of patients with HFRS. CONCLUSION: The findings of this study may provide systematic evidence to judge whether XBJ-T is an effective and safety intervention for HFRS. STUDY REGISTRATION NUMBER: INPLASY202040068.

Experimental evidence for the involvement of F0/F1 ATPase and subsequent P2Y12 receptor activation in prothymosin alpha-induced protection of retinal ischemic damage.

The inhibition of retinal ischemia-induced damage by post-ischemic prothymosin alpha (ProTα) was not affected in toll-like receptor 4 knockout (TLR4-/-) mice but blocked by the pretreatment with antibody against F0/F1 ATPase α- or ß-subunit, novel candidate for ProTα-receptor. In addition to the previous observation of ProTα-induced ATP release from cells, the present study showed a ProTα-induced enhancement of ATP hydrolysis activity of recombinant ATP5A1/5B complex. As the protection of retinal function by post-ischemic ProTα was abolished by anti-P2Y12 antibody, the activation of F0/F1 ATPase and subsequent P2Y12 receptor system may play roles in beneficial actions by post-ischemic ProTα.

Ethosomal Gel for Improving Transdermal Delivery of Thymosin ß-4.

PURPOSE: Thymosin ß-4(Tß-4) is a macromolecular protein drug with potential for drug development in wound repair but is limited by the shortcomings of macromolecular protein, such as large volumes, poor membrane permeability, and unstable physicochemical characteristics. Ethosomes could enhance cell membrane fluidity and reduce epidermal membrane density to make macromolecular drugs through the stratum corneum into the deeper layers of the skin easily. Herein, we developed and characterized a novel transdermal delivery vehicle to load macromolecular protein peptides and use Tß-4 as a model drug wrapped into ethosomes. METHODS: We used the orthogonal method to optimize the formulation of the ethosome preparation prepared by the ethonal infusion method. Ethosomal gels were characterized by using different analytical methods. Transdermal release rate in vitro have been demonstrated in Franz diffusion cells and the efficacy of drug-loaded nanocarriers in vivo was investigated in a mouse model. RESULTS: Optimized Tß-4 ethosomal gels have good physicochemical properties. The drug amounts of the cumulative release in the ethosomal gel within 5 hours were 1.67 times that of the T-ß4 gel in vitro release study, and the wound healing time of ethosomal gel group was only half of the T-ß4 gel group in vivo pharmacokinetic study. Compared with the free drug group, the ethosome preparation not only promotes the percutaneous absorption process of the macromolecular protein drugs but also shortened wound recovery time. CONCLUSION: Hence, we provide a possible good design for ethosomal gel system that can load macromolecular protein peptide drugs to achieve transdermal drug administration, promoting the percutaneous absorption of the drug and improving the effect.

Local Thymosin ß4 Gel Injection Prevents Esophageal Stricture after Circumferential Endoscopic Submucosal Dissection in a Porcine Model.

BACKGROUND: Endoscopic submucosal dissection (ESD) is widely used in the treatment of early esophageal cancer. However, the incidence of postoperative esophageal stricture is relatively high, especially after full circumferential ESD. Previous studies have shown that thymosin ß4 (Tß4) has anti-fibrotic activity and prevents scar formation. In this study, we investigated the safety and therapeutic effect of Tß4 injection in preventing esophageal stricture after circumferential ESD in a porcine model. METHODS: A total of 8 Bama pigs underwent esophageal circumferential ESD under anesthesia (n = 4 for experimental and control group). Local injection of Tß4 gel was administered in the experimental group. Follow-up endoscopy was conducted, and balloon dilation (EBD) was performed to prevent the occurrence of esophageal stricture. RESULTS: Esophageal stricture developed after circumferential ESD in all pigs. Local Tß4 gel injection has shortened resolution of the stricture (p = 0.012) and was associated with a lesser number of EBD sessions (p = 0.002). The severity of esophageal stricture was milder in the experimental group (p = 0.046 vs. control group). No adverse events occurred in the study. CONCLUSIONS: Local Tß4 gel injection appeared to be safe and effective for the prevention of esophageal stricture after circumferential ESD in a porcine model.

RGN-259 (thymosin ß4) improves clinically important dry eye efficacies in comparison with prescription drugs in a dry eye model.

This study evaluated the clinical activity of RGN-259 (thymosin ß4) in comparison with cyclosporine A (CsA), diquafosol (DQS), and lifitegrast (LFA) in a murine model of dry eye. The model was NOD.B10-H2b mice in a 30-40% humidified environment together with daily scopolamine hydrobromide injections for 10 days. After desiccation stress, all drugs were evaluated after 10 treatment days. RGN-259 increased tear production similar to that in the DQS- and LFA-treated mice while CsA was inactive. RGN-259 improved corneal smoothness and decreased fluorescein staining similar to that of LFA group while CsA and DQS were inactive. Corneal epithelial detachment was reduced by RGN-259, and DQS and LFA showed similar activity but the CsA was inactive. RGN-259 increased conjunctival goblet cells and mucin production comparable to that seen with CsA, while DQS and LFA were inactive. RGN-259 reduced the over-expression of inflammatory factors comparable to that with CsA and LFA, while DQS was inactive. RGN-259 increased mucin production comparable to that observed with CsA, while DQS and LFA were inactive. In conclusion, RGN-259 promoted recovery of mucins and goblet cells, improved corneal integrity, and reduced inflammation in a dry eye mouse model and was equal to or more effective than prescription treatments.

No effect of thymosin beta-4 on the expression of the transcription factor Islet-1 in the adult murine heart.

The transcription factor Islet-1 marks a progenitor cell population of the second heart field during cardiogenesis. In the adult heart Islet-1 expression is limited to the sinoatrial node, the ventricular outflow tract, and parasympathetic ganglia. The regenerative effect in the injured mouse ventricle of thymosin beta-4 (TB4), a 43-aminoacid peptide, was associated with increased Islet-1 immunostaining, suggesting the induction of an Islet-1-positive progenitor state by TB4. Here we aimed to reassess this effect in a genetic model. Mice from the reporter mouse line Isl1-nLacZ were primed with TB4 and subsequently underwent myocardial infarction. Islet-1 expression was assessed 2, 7, and 14 days after infarction. We detected only a single Islet-1+ cell in 8 TB4 treated and infarcted hearts which located outside of the sinoatrial node, the outflow tract or cardiac ganglia (in ~2500 sections). Two cells were identified in 5 control infarcted hearts. TB4 did not induce LacZ positivity in ventricular explants cultures of Isl1-nLacZ mice nor did it affect the density of LacZ+ cells in explant cultures of nLacZ+ regions of the heart. In summary, we found no evidence that TB4 reactivates Islet-1 expression in adult mouse ventricle.

Thymosin ß4 Deficiency Exacerbates Renal and Cardiac Injury in Angiotensin-II-Induced Hypertension.

Thymosin ß4 (Tß4), a ubiquitous peptide, regulates several cellular processes that include cell morphology, wound healing, and inflammatory response. Administration of exogenous Tß4 is protective in diabetic nephropathy and in a unilateral ureteral obstruction model. However, the role of endogenous Tß4 in health and disease conditions remains unclear. To elucidate the pathophysiological role of endogenous Tß4 in hypertension, we examined angiotensin-II (Ang-II)-induced renal and cardiac damage in Tß4 knockout (Tß4 KO) mice. Tß4 KO and wild-type C57BL/6 mice were infused continuously for 6 weeks with either vehicle or Ang-II (980 ng/kg per minute). At baseline, Tß4 deficiency did not affect renal and cardiac function. Systolic blood pressure in the Ang-II group was similar in wild-type and Tß4 KO mice (wild-type Ang-II, 179.25±10.11 mm Hg; Tß4 KO Ang-II, 169.81±6.54 mm Hg). Despite the similar systolic blood pressure after Ang-II infusion, Tß4-deficient mice had dramatically increased albuminuria and decreased nephrin expression in the kidney (P<0.005). In the heart of Tß4 KO mice, Ang-II reduced ejection fraction and shortening fraction (ejection fraction: wild-type Ang-II 77.95%±1.03%; Tß4 KO Ang-II 62.58%±3.25%; P<0.005), which was accompanied by cardiac hypertrophy and left ventricular dilatation. In addition, renal and cardiac infiltration of CD68 macrophages, intercellular adhesion molecule-1, and total collagen content were increased after Ang-II infusion in Tß4 KO mice (P<0.005). Overall, our data indicate that endogenous Tß4 is crucial in preventing tissue injury from Ang-II-induced hypertension. This study gives new insights into the protective role of endogenous Tß4 in hypertensive end-organ damage.

Immunotherapy for hepatitis B in the direct acting antiviral era: Reevaluating the thymosin α1 efficacy trials in the light of a combination therapy approach.

Hepatitis B virus (HBV) causes both acute and chronic hepatitis and infects large numbers of individuals worldwide. Unfortunately, prediction of typical clinical outcome is problematic and there is considerable variability in the frequency, duration and severity of disease progression. The mainstay of HBV treatment is directed towards the suppression of HBV replication by nucleos(t)ide analogs (NUCs). The use of immunomodulators such as α-Interferon and thymosin α1 can, in select patients, results in elimination of both HBsAg and HBeAg. Given the observation that viral clearance is most effective in the presence of a strong immune response, this review summarizes data suggesting that the use of a combination of an immune modulator such as Tα1 with a highly effective NUC may result in a more successful therapeutic approach in patients with chronic hepatitis B (CHB). Results from small studies using combination Tα1 and NUCs are encouraging, and ongoing clinical trials combining entecavir with Tα1 are anticipated to provide important data assessing the use of a combination of Tα1 with a NUC to achieve resolution of CHB.

Thymosin ß4 alleviates renal fibrosis and tubular cell apoptosis through TGF-ß pathway inhibition in UUO rat models.

BACKGROUND: Thymosin ß4 (Tß4) is closely associated with the cytoskeleton, inflammation, wound healing, angiogenesis, apoptosis, and myocardial regeneration, but the effects of Tß4 treatment on chronic renal tubular interstitial fibrosis (CRTIF) are poorly known. This study aimed to examine the effects of Tß4 on the renal apoptosis and the expression of transforming growth factor (TGF-ß), E-cadherin, and α-smooth muscle actin (α-SMA) in CRTIF rat models. METHODS: Male SD rats were randomized into four groups (sham group, unilateral ureteral obstruction (UUO) group, UUO + low-dose Tß4 group, and UUO + high-dose Tß4 group). The pathological changes of kidney tissue and its function were assessed two weeks after UUO. In renal interstitial tissue,TGF-ß, E-cadherin and α-SMA expression was detected by western blot. In tubular epithelial cells, E-cadherin and α-SMA expression was detected using Real-time qPCR and western blot. Cell apoptosis of rat renal interstitial tissue and tubular epithelial cells was evaluated by immunofluorescence and western blot. RESULTS: Two weeks after UUO, no differences in blood urea nitrogen and creatinine were observed between the four groups (P > 0.05). Compared to the UUO group, Tß4 treatment decreased the 24-h proteinuria (P < 0.001) and reduced the area of pathological change (P < 0.01); this effect was more apparent in the UUO + high-dose Tß4 group. Compared to the UUO group, a significant decrease in TGF-ß and α-SMA protein expression was observed in the high-dose Tß4 group. The level of E-cadherin protein was lower in the UUO group than the Tß4 groups, and high-dose Tß4 treatment further increased E-cadherin expression and improved cell apoptosis in the renal interstitial tissue. Analysis of in vitro tubular epithelial cells showed that α-SMA mRNA and protein expression decreased, while E-cadherin mRNA and protein expression increased by Tß4 treatment. Similarly, these changes were more significant in the UUO + high-dose Tß4 group. Tß4 treatment improved the apoptosis of In vitro tubular epithelial cells compared with pure TGF-ß stimulation, and equally, the decrease of apoptosis was more apparent in the TGF-ß + high-dose Tß4 group. CONCLUSIONS: Tß4 treatment might alleviate the renal fibrosis and apoptosis of tubular epithelial cells through TGF-ß pathway inhibition in UUO rats with CRTIF.

Immunopotentiator Thymosin Alpha-1 Promotes Neurogenesis and Cognition in the Developing Mouse via a Systemic Th1 Bias.

In early life, the immune system plays an essential role in brain development. In our study, the immunopotentiator thymosin alpha-1 (Ta1) was peripherally administered to neonatal mice to explore whether the peripheral immunopotentiator affects neurodevelopment and cognition, and to further investigate the relevant mechanism. Compared with the control group, the Ta1 mice displayed better cognitive abilities in early life. The numbers of 5-bromodeoxyuridine (BrdU)+, nestin+, T-box transcription factor 2 (Tbr2)+, BrdU+/doublecortin (DCX)+, BrdU+/ionized calcium-binding adaptor molecule 1 (Iba1)+, and BrdU+/neuronal nuclei (NeuN)+ cells in the hippocampus were increased in the Ta1 group, accompanied by increased interleukin-4 (IL-4), interferon-gamma, brain-derived neurotrophic factor, nerve growth factor, and insulin-like growth factor-1 as well as decreased IL-6 and tumor necrosis factor-α. Furthermore, the Ta1-group showed a Th1-polarized immune response, and the neurotrophic factors were positively associated with the Th1/Th2 ratio. More importantly, administration of Ta1 blocked lipopolysaccharide-induced impairment of hippocampal neurogenesis in early life. These findings suggest that peripheral Ta1 contributes to neurogenesis and cognition probably through a systemic Th1 bias, as well as neuroprotection against LPS infection by Ta1.

Targeted delivery of thymosin beta 4 to the injured myocardium using CREKA-conjugated nanoparticles.

PURPOSE: Thymosin beta 4 (Tß4) has multiple beneficial facets for myocardial injury, but its efficiency is limited by the low local concentration within the infarct. Here, we established a Tß4 delivery system for cardiac repair based on the interaction between the abundant fibrin in the infarct zone and the fibrin-targeting moiety clot-binding peptide cysteine-arginine-glutamic acid-lysine-alanine (CREKA). METHODS AND RESULTS: CREKA and Tß4 were conjugated to nanoparticles (CNP-Tß4). In vitro binding test revealed that CNP-Tß4 had a significant binding ability to the surface of fibrin clots when compared to the control clots (NP-Tß4). Based on the validation of fibrin expression in the early stage of ischemia injury, CNP-Tß4 was intravenously administered to mice with acute myocardial ischemia-reperfusion injury. CNP-Tß4 revealed a stronger fibrin-targeting ability than the NP-Tß4 group and accumulated mainly in the infarcted area and colocalized with fibrin. Subsequently, treatment with CNP-Tß4 resulted in a better therapeutic effect. CONCLUSION: CRKEA modification favored Tß4 accumulation and retention in the infarcted region, leading to augmented functional benefits. Fibrin-targeting delivery system represents a generalizable platform technology for regenerative medicine.

Thymalfasin, a promising adjuvant therapy in small hepatocellular carcinoma after liver resection.

There is limited information available concerning the effect of thymalfasin (Tα1) as an adjuvant therapy in hepatocellular carcinoma (HCC) patient who received liver resection. The present study aimed to evaluate whether Tα1 can improve the prognosis of small HCC patients after liver resection.A total of 206 patients with small HCC who underwent liver resection were analyzed in our retrospective cohort study. Patients were divided into 2 groups: group A (resection + Tα1, n = 44) and group B (resection, n = 162). Clinical data, overall survival (OS), and recurrence-free survival (RFS) were compared. Prognostic factors were identified using multivariate analysis.After a median follow-up of 47.0 months, 134 patients (65%) had recurrence, and 62 patients (30.09%) died. The 1, 3, and 5-year OS rate of patients in group A was 97.7%, 90.6%, and 82.9%, respectively, and 95.1%, 80.5%, and 62.9%, respectively, for patients in group B (P = .014). The 1, 3, and 5-year RFS rate of patients in group A was 70.5%, 56.8%, and 53.3%, respectively, and 65.8%, 41.3%, and 32.1%, respectively, for patients in group B (P = .015). Multivariate analysis indicated that Tα1 was an independent prognostic factor for both OS (P = .015, hazard ratio 0.349, 95% confidence interval 0.149-0.816) and RFS (P = .019, hazard ratio 0.564, 95% confidence interval 0.349-0.910).Tα1 as an adjuvant therapy after liver resection may improve the prognosis of small HCC patients after liver resection.

Diabetes Mellitus-Induced Microvascular Destabilization in the Myocardium.

BACKGROUND: Diabetes mellitus causes microcirculatory rarefaction and may impair the responsiveness of ischemic myocardium to proangiogenic factors. OBJECTIVES: This study sought to determine whether microvascular destabilization affects organ function and therapeutic neovascularization in diabetes mellitus. METHODS: The authors obtained myocardial samples from patients with end-stage heart failure at time of transplant, with or without diabetes mellitus. Diabetic (db) and wild-type (wt) pigs were used to analyze myocardial vascularization and function. Chronic ischemia was induced percutaneously (day 0) in the circumflex artery. At day 28, recombinant adeno-associated virus (rAAV) (5 × 1012 viral particles encoding vascular endothelial growth factor-A [VEGF-A] or thymosin beta 4 [Tß4]) was applied regionally. CD31+ capillaries per high power field (c/hpf) and NG2+ pericyte coverage were analyzed. Global myocardial function (ejection fraction [EF] and left ventricular end-diastolic pressure) was assessed at days 28 and 56. RESULTS: Diabetic human myocardial explants revealed capillary rarefaction and pericyte loss compared to nondiabetic explants. Hyperglycemia in db pigs, even without ischemia, induced capillary rarefaction in the myocardium (163 ± 14 c/hpf in db vs. 234 ± 8 c/hpf in wt hearts; p < 0.005), concomitant with a distinct loss of EF (44.9% vs. 53.4% in nondiabetic controls; p < 0.05). Capillary density further decreased in chronic ischemic hearts, as did EF (both p < 0.05). Treatment with rAAV.Tß4 enhanced capillary density and maturation in db hearts less efficiently than in wt hearts, similar to collateral growth. rAAV.VEGF-A, though stimulating angiogenesis, induced neither pericyte recruitment nor collateral growth. As a result, rAAV.Tß4 but not rAAV.VEGF-A improved EF in db hearts (34.5 ± 1.4%), but less so than in wt hearts (44.8 ± 1.5%). CONCLUSIONS: Diabetes mellitus destabilized microvascular vessels of the heart, affecting the amplitude of therapeutic neovascularization via rAAV.Tß4 in a translational large animal model of hibernating myocardium.

A Tobacco-Derived Thymosin ß4 Concatemer Promotes Cell Proliferation and Wound Healing in Mice.

Thymosin ß4 (Tß4) is a peptide that is known to play important roles in protection, regeneration, and remodeling of injured tissues in humans, and that shows great promise in a range of clinical applications. However, current strategies to Tß4 are insufficient to meet growing demand and have a number of limitations. In this current study we investigated whether expression of recombinant Tß4 in plants, specifically in tobacco (Nicotiana tabacum) leaves, represents an effective approach. To address this question, a 168 bp Tß4 gene optimized for tobacco codon usage bias was constitutively expressed in tobacco as a 4-unit repeat concatemer, fused to a polyhistidine tag. Quantitative polymerase chain reaction and Western blot analyses were used to verify 4×Tß4 expression in 14 transgenic tobacco lines and enzyme-linked immunosorbent assay analysis indicated 4×Tß4 protein concentrations as high as 3 µg/g of fresh weight in the leaves. We observed that direct administration of tobacco-derived Tß4 was more effective than Tß4 either obtained commercially or derived from expression in Escherichia coli at promoting splenocyte proliferation in vitro and wound healing in mice through an endothelial migration assay. This study provides new insights into the development of plant-derived therapeutic proteins and their application by direct administration.

Immune Modulation with Thymosin Alpha 1 Treatment.

Thymosin alpha 1 (Ta1) is a peptide originally isolated from thymic tissue as the compound responsible for restoring immune function to thymectomized mice. Ta1 has a pleiotropic mechanism of action, affecting multiple immune cell subsets that are involved in immune suppression. Ta1 acts through Toll-like receptors in both myeloid and plasmacytoid dendritic cells, leading to activation and stimulation of signaling pathways and initiation of production of immune-related cytokines. Due to the immune stimulating effects of Ta1, the compound would be expected to show utility for treatment of immune suppression, whether related to aging or to diseases such as infection or cancer. Extensive studies in both the preclinical and clinical setting will be summarized in the subsequent sections. These studies have demonstrated improvements in immune system cell subsets and the potential of Ta1 for the treatment of a range of diseases.

Thymosin ß4: Roles in Development, Repair, and Engineering of the Cardiovascular System.

The burden of cardiovascular disease is a growing worldwide issue that demands attention. While many clinical trials are ongoing to test therapies for treating the heart after myocardial infarction (MI) and heart failure, there are few options doctors able to currently give patients to repair the heart. This eventually leads to decreased ventricular contractility and increased systemic disease, including vascular disorders that could result in stroke. Small peptides such as thymosin ß4 (Tß4) are upregulated in the cardiovascular niche during fetal development and after injuries such as MI, providing increased neovasculogenesis and paracrine signals for endogenous stem cell recruitment to aid in wound repair. New research is looking into the effects of in vivo administration of Tß4 through injections and coatings on implants, as well as its effect on cell differentiation. Results so far demonstrate Tß4 administration leads to robust increases in angiogenesis and wound healing in the heart after MI and the brain after stroke, and can differentiate adult stem cells toward the cardiac lineage for implantation to the heart to increase contractility and survival. Future work, some of which is currently in clinical trials, will demonstrate the in vivo effect of these therapies on human patients, with the goal of helping the millions of people worldwide affected by cardiovascular disease.

The Efficacy and Immunomodulatory Effects of Ulinastatin and Thymosin α1 for Sepsis: A Systematic Review and Meta-Analysis.

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.

Thymosin α1 plus routine treatment inhibit inflammatory reaction and improve the quality of life in AECOPD patients.

CONTEXT: Thymosin α1 (Tα1) is considered to be a promising immunomodulatory drug and could balance immunity and tolerance in immune tolerance and autoimmunity. OBJECTIVE: To explore the efficacy of Tα1 plus routine complex treatment in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). METHODS: Eighty-four AECOPD patients were enrolled and randomized into an experimental group and a control group. All patients received the routine treatment. Additionally, the experimental group received subcutaneous injections of Tα1 while the control group received placebo. Four weeks later, the curative effect of treatment and immune function of both groups were analyzed. RESULTS: Partial pressures of oxygen (PaO2), PaCO2, and pulmonary function of the experimental group improved after treatment compared to that recorded prior to treatment and that observed for the control group (p < 0.01, both). The CD4(+) T cell count, serum interferon (IFN)-γ levels, and the ratios of CD4(+)/CD8(+) and IFN-γ/interleukin (IL)-4 increased in both groups (p < 0.01), while the CD8(+) T cell count and levels of IL-4, IL-8, and leukotrienes B4 (LTB4) decreased as expected (p < 0.01). Meanwhile, the above-mentioned indices of the experimental group improved significantly compared to the indices of the control group (p < 0.05 or 0.01). CONCLUSIONS: Tα1 plus routine treatment could improve the immune function of AECOPD patients and inhibit the inflammatory reaction, thus reducing the recurrence of chronic obstructive pulmonary disease (COPD).

Thymosin ß4 significantly reduces the signs of dryness in a murine controlled adverse environment model of experimental dry eye.

OBJECTIVE: Dry eye syndrome is a common condition that affects up to 20% of the population aged 45 and older. There are no successful treatments to date. The goal of this research was to determine the efficacy of various doses and the optimal frequency of thymosin ß4 (Tß4) treatment in a murine severe dry eye model. RESEARCH DESIGN AND METHODS: The study was performed using a controlled adverse environment chamber (CAE) in combination with scopolamine to induce moderate to severe dry eye in mice. The study included five mice per group and tested six different doses of Tß4 twice per day for 12 days. Tß4 at 0.1% was also administered 2 - 4 times per day for 12 days. Healing was measured by fluorescein staining. MAIN OUTCOME MEASURES: Tß4 significantly reduced the signs of dry eye relative to controls. The treatment effect was more pronounced than the positive controls, doxycycline and Restasis (cyclosporine 0.05%). Active doses of 0.1 and 0.5% were determined, and it was found that the frequency of dosing at 2 times per day was the most effective for healing. CONCLUSIONS: Tß4 has the potential to be an important new effective therapeutic for dry eye.