The purpose of this meta-analysis was to determine the effect of bariatric surgery on circulating PAI-1. The meta-analysis was provided by comprehensive meta-analysis (CMA) V4 software. Meta-analysis of 33 studies showed a significant decrease in circulating PAI-1 after bariatric surgery (p < 0.001). A significant reduction was observed for two types of surgery) (p < 0.001 for LSG and p < 0.001 for RYGB). Furthermore, there was a significant change in circulating PAI-1 based on the follow-up duration (p < 0.001 for follow-up < 12 months and p < 0.001 for follow-up ≥ 12). We showed that bariatric surgery changed PAI-1 level significantly and changes in BMI after surgery were not related to PAI-1 alteration. Furthermore, this result was consistent based on follow-up duration and type of surgery.

BACKGROUND: Fibrates are widely used in the treatment of dyslipidemia and associated metabolic abnormalities; however, their effects on adipokines are unclear.
OBJECTIVE: This meta-analysis of clinical trials aimed to evaluate the effect of fibrates on circulating adipokine levels.
METHODS: Only randomized controlled trials investigating the impact/effect of fibrate treatment on circulating adipokine levels were included from searches in PubMed-Medline, SCOPUS, ClinicalTrials.gov, Web of Science, and Google Scholar databases. A random effects model and the generic inverse variance method were used for the meta-analysis. Sensitivity analysis was conducted using the leave-one-out method.
RESULTS: This meta-analysis of 22 clinical trials showed a significant reduction on/in leptin (WMD: -1.58 ng/mL, 95% CI: -2.96, -0.20, p = 0.02, I2 = 0%), plasminogen activator inhibitor-1 (PAI-1) (WMD: -13.86 ng/mL, 95% CI: -26.70, -1.03, p = 0.03, I2 = 99%), and visfatin (WMD: -1.52 ng/mL, 95% CI: -2.49, -0.56, p = 0.002, I2 = 0%) after fibrate therapy; no significant effect was observed on adiponectin (WMD: -0.69 µg/ml, 95% CI: -1.40, 0.02, p = 0.06, I2 = 83%) and resistin (WMD: -2.27 ng/mL, 95% CI: -7.11, 2.57, p = 0.36, I2 = 0%). The sensitivity analysis was robust only for visfatin, while the effect size was sensitive to one arm for leptin, four for adiponectin, and two for PAI-1.
CONCLUSIONS: This meta-analysis showed that fibrate treatment significantly improves adipokine levels with a decrease in leptin, PAI-1, and visfatin, suggesting potential additional clinical therapeutic benefits through/of fibrate treatment on adipose tissue.

Adipocytes are a known source of stem cells. They are easy to harvest, and are a suitable candidate for autogenous grafts. Adipose derived stem cells (ADSCs) have multiple target tissues which they can differentiate into, including bone and cartilage. In adipose tissue, ADSCs are able to differentiate, as well as providing energy and a supply of cytokines/hormones to manage the hypoxic and lipid/hormone saturated adipose environment. The plasminogen activation system (PAS) controls the majority of proteolytic activities in both adipose and wound healing environments, allowing for rapid cellular migration and tissue remodelling. While the primary activation pathway for PAS occurs through the urokinase plasminogen activator (uPA), which is highly expressed by endothelial cells, its function is not limited to enabling revascularisation. Proteolytic activity is dependent on protease activation, localisation, recycling mechanisms and substrate availability. uPA and uPA activated plasminogen allows pluripotent cells to arrive to new local environments and fulfil the niche demands. However, overstimulation, the acquisition of a migratory phenotype and constant protein turnover can be unconducive to the formation of structured hard and soft tissues. To maintain a suitable healing pattern, the proteolytic activity stimulated by uPA is modulated by plasminogen activator inhibitor 1. Depending on the physiological settings, different parts of the remodelling mechanism are activated with varying results. Utilising the differences within each microenvironment to recreate a desired niche is a valid therapeutic bio-engineering approach. By controlling the rate of protein turnover combined with a receptive stem cell lineage, such as ADSC, a novel avenue on the therapeutic opportunities may be identified, which can overcome limitations, such as scarcity of stem cells, low angiogenic potential or poor host tissue adaptation.

Plasminogen activator inhibitor-1 (PAI-1) is the main physiological inhibitor of plasminogen activators (PAs) and is therefore an important inhibitor of the plasminogen/plasmin system. Being the fast-acting inhibitor of tissue-type PA (tPA), PAI-1 primarily attenuates fibrinolysis. Through inhibition of urokinase-type PA (uPA) and interaction with biological ligands such as vitronectin and cell-surface receptors, the function of PAI-1 extends to pericellular proteolysis, tissue remodeling and other processes including cell migration. This review aims at providing a general overview of the properties of PAI-1 and the role it plays in many biological processes and touches upon the possible use of PAI-1 inhibitors as therapeutics.

Background: A 4G/5G polymorphism in the promoter region of the plasminogen activator inhibitor type 1 (PAI-1) gene has been reported to enhance the plasma levels of PAI-1, which plays an important role in fibrinolysis disorders and venous thromboembolism, but a large number of studies have reported inconclusive results. Therefore, we performed a meta-analysis to analysis these associations. Materials and methods: We performed a publication search for articles published before April 2019 by using the electronic databases of web of Science, Embase, PubMed, CNKI, CBM and WanFang data with the following terms \"PAI-1\", \"polymorphism\", \"Venous Thromboembolism\". Two investigators independently extracted data and assessed study quality. Statistical analyses were undertaken using Stata 14.0. Results: A total of 27 studies, with 3135 patients and 5346 controls were included. Overall, the variant PAI-1 4G/4G and PAI-1 4G/5G was associated with venous thromboembolism risk, compared with the PAI-1 5G/5G allele in the populations included in the analysis. Stratified analysis revealed that PAI-1 4G/4G and PAI-1 4G/5G genotypes were associated with an increased VTE risk among Asia populations in all five genetic models. Conclusions: The PAI-1 4G/5G polymorphism may be a potential biomarker of VTE risk, particularly in Asia populations. Further larger studies with multi-ethnic populations are required to further assess the association between PAI-1 4G/4G polymorphisms and VTE risk.

BACKGROUND: Thromboembolism, including deep venous thrombosis and pulmonary embolism, is a grave threat to patients undergoing total joint replacement. Using a systematic review and meta-analysis we asked whether gene mutations or polymorphisms could be risk factors for thrombosis after arthroplasty.
METHODS: We performed a comprehensive search of Medline, PubMed, Embase, Cochrane databases, China National Knowledge Infrastructure (CNKI), and Google Scholar, and identified 19 studies detailing genetic investigations of patients with thromboembolism following joint replacement.
RESULTS: Our meta-analyses included 5149 patients who underwent arthroplasty surgery. Significant associations with venous thromboembolism were identified for factor G1691A (odds ratio (OR) 1.41, 95% confidence interval (CI) 1.03 - 1.94, p=0.03), prothrombin G20210A (OR 2.16, 95% CI, 1.27- 3.69, p=0.005), and MTHFR/C677T/TT (OR 2.36, 95% CI 1.03 - 5.42, p=0.04) in Caucasian populations. No significant gene mutation was identified in Asian populations.
CONCLUSIONS: This study suggests a way to identify patients scheduled for arthroplasty who are at higher risk of thrombosis, enabling individualized treatment.