Showing papers by "Li Yang published in 2022"

Pan-cancer single-cell analysis reveals the heterogeneity and plasticity of cancer-associated fibroblasts in the tumor microenvironment

Abstract: Abstract Cancer-associated fibroblasts (CAFs) are the predominant components of the tumor microenvironment (TME) and influence cancer hallmarks, but without systematic investigation on their ubiquitous characteristics across different cancer types. Here, we perform pan-cancer analysis on 226 samples across 10 solid cancer types to profile the TME at single-cell resolution, illustrating the commonalities/plasticity of heterogenous CAFs. Activation trajectory of the major CAF types is divided into three states, exhibiting distinct interactions with other cell components, and relating to prognosis of immunotherapy. Moreover, minor CAF components represent the alternative origin from other TME components (e.g., endothelia and macrophages). Particularly, the ubiquitous presentation of endothelial-to-mesenchymal transition CAF, which may interact with proximal SPP 1 + tumor-associated macrophages, is implicated in endothelial-to-mesenchymal transition and survival stratifications. Our study comprehensively profiles the shared characteristics and dynamics of CAFs, and highlight their heterogeneity and plasticity across different cancer types. Browser of integrated pan-cancer single-cell information is available at https://gist-fgl.github.io/sc-caf-atlas/ .

Engineering strategies to enhance oncolytic viruses in cancer immunotherapy

Abstract: Oncolytic viruses (OVs) are emerging as potentially useful platforms in treatment methods for patients with tumors. They preferentially target and kill tumor cells, leaving healthy cells unharmed. In addition to direct oncolysis, the essential and attractive aspect of oncolytic virotherapy is based on the intrinsic induction of both innate and adaptive immune responses. To further augment this efficacious response, OVs have been genetically engineered to express immune regulators that enhance or restore antitumor immunity. Recently, combinations of OVs with other immunotherapies, such as immune checkpoint inhibitors (ICIs), chimeric antigen receptors (CARs), antigen-specific T-cell receptors (TCRs) and autologous tumor-infiltrating lymphocytes (TILs), have led to promising progress in cancer treatment. This review summarizes the intrinsic mechanisms of OVs, describes the optimization strategies for using armed OVs to enhance the effects of antitumor immunity and highlights rational combinations of OVs with other immunotherapies in recent preclinical and clinical studies.

Development of Innovative Biomaterials and Devices for the Treatment of Cardiovascular Diseases

Abstract: Cardiovascular diseases have become the leading cause of death worldwide. The increasing burden of cardiovascular diseases has become a major public health problem and how to carry out efficient and reliable treatment of cardiovascular diseases has become an urgent global problem to be solved. Recently, implantable biomaterials and devices, especially minimally invasive interventional ones, such as vascular stents, artificial heart valves, bioprosthetic cardiac occluders, artificial graft cardiac patches, atrial shunts, and injectable hydrogels against heart failure, have become the most effective means in the treatment of cardiovascular diseases. Herein, an overview of the challenges and research frontier of innovative biomaterials and devices for the treatment of cardiovascular diseases is provided, and their future development directions are discussed.

A Polyphenol-Network-Mediated Coating Modulates Inflammation and Vascular Healing on Vascular Stents.

Abstract: Localized drug delivery from drug-eluting stents (DESs) to target sites provides therapeutic efficacy with minimal systemic toxicity. However, DESs failure may cause thrombosis, delay arterial healing, and impede re-endothelialization. Bivalirudin (BVLD) and nitric oxide (NO) promote arterial healing. Nevertheless, it is difficult to combine hydrophilic signal molecules with hydrophobic antiproliferative drugs while maintaining their bioactivity. Here, we fabricated a micro- to nanoscale network assembly consisting of copper ion and epigallocatechin gallate (EGCG) via π-π interactions, metal coordination, and oxidative polymerization. The network incorporated rapamycin and immobilized BVLD by the thiol-ene "click" reaction and provided sustained rapamycin and NO release. Unlike rapamycin-eluting stents, those coated with the EGCG-Cu-rapamycin-BVLD complex favored competitive endothelial cell (EC) growth over that of smooth muscle cells, exhibited long-term antithrombotic efficacy, and attenuated the negative impact of rapamycin on the EC. In vivo stent implantation demonstrated that the coating promoted endothelial regeneration and hindered restenosis. Therefore, the polyphenol-network-mediated surface chemistry can be an effective strategy for the engineering of multifunctional surfaces.

Construction of multifunctional wound dressings with their application in chronic wound treatment.

Abstract: As the prevalence of diabetes increases year by year and the aging population continues to intensify in the world, chronic wounds such as diabetic foot ulcers and pressure ulcers have become serious problems that threaten people's health, and have brought an enormous burden to the world healthcare system. Conventional clinical treatment of chronic wounds relies on non-specific topical care (including debridement, infection/inflammation control, and frequent wound dressing changes), which can alleviate disease progression and reduce patient suffering to a certain extent, but the overall cure rate is less than 50% and the recurrence rate is high. Traditional wound dressings such as gauze, hydrocolloids, films and foams are single-function, acting as a physical barrier or absorbing exudates, and cannot meet all the needs of the entire chronic wound healing process. Recently, a large number of novel functional dressings have been reported for chronic wound repair. Based on the progress on wound dressings in recent years and the relevant research experience of our group, the review summarizes and discusses the progress on multifunctional wound dressings (such as microneedles, sponges and hydrogels) with anti-inflammatory, antioxidant, antibacterial, pro-angiogenic and tissue adhesive functions in detail. At the same time, the various responsive mechanisms (in vivo microenvironment or in vitro stimulation) of the smart multifunctional wound dressing are also analyzed in detail. It is expected that the review could provide some inspiration and suggestions for research on dressings for chronic wound treatment.

Multiplexed nanomaterial-assisted laser desorption/ionization for pan-cancer diagnosis and classification

Abstract: As cancer is increasingly considered a metabolic disorder, it is postulated that serum metabolite profiling can be a viable approach for detecting the presence of cancer. By multiplexing mass spectrometry fingerprints from two independent nanostructured matrixes through machine learning for highly sensitive detection and high throughput analysis, we report a laser desorption/ionization (LDI) mass spectrometry-based liquid biopsy for pan-cancer screening and classification. The Multiplexed Nanomaterial-Assisted LDI for Cancer Identification (MNALCI) is applied in 1,183 individuals that include 233 healthy controls and 950 patients with liver, lung, pancreatic, colorectal, gastric, thyroid cancers from two independent cohorts. MNALCI demonstrates 93% sensitivity at 91% specificity for distinguishing cancers from healthy controls in the internal validation cohort, and 84% sensitivity at 84% specificity in the external validation cohort, with up to eight metabolite biomarkers identified. In addition, across those six different cancers, the overall accuracy for identifying the tumor tissue of origin is 92% in the internal validation cohort and 85% in the external validation cohort. The excellent accuracy and minimum sample consumption make the high throughput assay a promising solution for non-invasive cancer diagnosis.

Multiplexed nanomaterial-assisted laser desorption/ionization for pan-cancer diagnosis and classification

Abstract: As cancer is increasingly considered a metabolic disorder, it is postulated that serum metabolite profiling can be a viable approach for detecting the presence of cancer. By multiplexing mass spectrometry fingerprints from two independent nanostructured matrixes through machine learning for highly sensitive detection and high throughput analysis, we report a laser desorption/ionization (LDI) mass spectrometry-based liquid biopsy for pan-cancer screening and classification. The Multiplexed Nanomaterial-Assisted LDI for Cancer Identification (MNALCI) is applied in 1,183 individuals that include 233 healthy controls and 950 patients with liver, lung, pancreatic, colorectal, gastric, thyroid cancers from two independent cohorts. MNALCI demonstrates 93% sensitivity at 91% specificity for distinguishing cancers from healthy controls in the internal validation cohort, and 84% sensitivity at 84% specificity in the external validation cohort, with up to eight metabolite biomarkers identified. In addition, across those six different cancers, the overall accuracy for identifying the tumor tissue of origin is 92% in the internal validation cohort and 85% in the external validation cohort. The excellent accuracy and minimum sample consumption make the high throughput assay a promising solution for non-invasive cancer diagnosis.

Mesenchymal Stem Cell-Derived Extracellular Vesicles in Liver Immunity and Therapy

Abstract: Mesenchymal stem cells (MSCs), as the most common cell source for stem cell therapy, play an important role in the modulation of innate and adaptive immune responses and have been widely used in clinical trials to treat autoimmune and inflammatory diseases. Recent experimental and clinical studies have shown that MSC-derived extracellular vesicles (MSC-EVs) can inhibit the activation and proliferation of a variety of proinflammatory cells, such as Th1, Th17 and M1 macrophages, reducing the secretion of proinflammatory cytokines, while promoting the proliferation of anti-inflammatory cells, such as M2 macrophages and Tregs, and increasing the secretion of anti-inflammatory cytokines, thus playing a role in immune regulation and exhibiting immunomodulatory functions. Besides MSC-EVs are more convenient and less immunogenic than MSCs. There is growing interest in the role of MSC-EVs in liver diseases owing to the intrinsic liver tropism of MSC-EVs. In this review, we focus on the immunomodulatory effects of MSC-EVs and summarize the pivotal roles of MSC-EVs as a cell-free therapy in liver diseases, including NAFLD, AIH, acute liver failure, liver fibrosis and hepatic ischemia–reperfusion injury. Moreover, we provide a concise overview of the potential use and limits of MSC-EVs in clinical application.

A thrombin-triggered self-regulating anticoagulant strategy combined with anti-inflammatory capacity for blood-contacting implants

Abstract: Interrelated coagulation and inflammation are impediments to endothelialization, a prerequisite for the long-term function of cardiovascular materials. Here, we proposed a self-regulating anticoagulant coating strategy combined with anti-inflammatory capacity, which consisted of thrombin-responsive nanogels with anticoagulant and anti-inflammatory components. As an anticoagulant, rivaroxaban was encapsulated in nanogels cross-linked by thrombin-cleavable peptide and released upon the trigger of environmental thrombin, blocking the further coagulation cascade. The superoxide dismutase mimetic Tempol imparted the antioxidant property. Polyphenol epigallocatechin gallate (EGCG), in addition to its anti-inflammatory function in synergy with Tempol, also acted as a weak cross-linker to stabilize the coating. The effectiveness and versatility of this coating were validated using two typical cardiovascular devices as models, biological valves and vascular stents. It was demonstrated that the coating worked as a precise strategy to resist coagulation and inflammation, escorted reendothelialization on the cardiovascular devices, and provided a new perspective for designing endothelium-like functional coatings.

Platelet Membrane-Coated Nanocarriers Targeting Plaques to Deliver Anti-CD47 Antibody for Atherosclerotic Therapy

Abstract: Atherosclerosis, the principle cause of cardiovascular disease (CVD) worldwide, is mainly characterized by the pathological accumulation of diseased vascular cells and apoptotic cellular debris. Atherogenesis is associated with the upregulation of CD47, a key antiphagocytic molecule that is known to render malignant cells resistant to programmed cell removal, or “efferocytosis.” Here, we have developed platelet membrane-coated mesoporous silicon nanoparticles (PMSN) as a drug delivery system to target atherosclerotic plaques with the delivery of an anti-CD47 antibody. Briefly, the cell membrane coat prolonged the circulation of the particles by evading the immune recognition and provided an affinity to plaques and atherosclerotic sites. The anti-CD47 antibody then normalized the clearance of diseased vascular tissue and further ameliorated atherosclerosis by blocking CD47. In an atherosclerosis model established in ApoE−/− mice, PMSN encapsulating anti-CD47 antibody delivery significantly promoted the efferocytosis of necrotic cells in plaques. Clearing the necrotic cells greatly reduced the atherosclerotic plaque area and stabilized the plaques reducing the risk of plaque rupture and advanced thrombosis. Overall, this study demonstrated the therapeutic advantages of PMSN encapsulating anti-CD47 antibodies for atherosclerosis therapy, which holds considerable promise as a new targeted drug delivery platform for efficient therapy of atherosclerosis.

Microfibrillated cellulose-enhanced carboxymethyl chitosan/oxidized starch sponge for chronic diabetic wound repair.

Abstract: Herein, a novel microfibrillated cellulose (MFC) reinforced natural polymer-based sponge composed of carboxymethyl chitosan (CMC) and oxidized starch (OS) with hemostatic, repairing-promoting, and antimicrobial performances was fabricated for chronic wound repair. When the content of MFC reached 1.2 wt%, the prepared sponge exhibited ultra-fast water or blood-trigged shape recovery property within 3 s. Moreover, sponge was functionally modified with silver nanoparticles (AgNPs) and recombinant humanized collagen type III (rhCol III). The AgNPs and rhCol III loaded sponge (A-Ag/III) could effectively kill a broad spectrum of pathogenic microbes, promote the proliferation and migration of L929 cells in vitro. Due to their erythrocyte-aggregating ability and positive-charge feature of CMC, the A-Ag/III displayed rapid hemostasis ability. Furthermore, the in vivo animal experiment demonstrated the A-Ag/III could promote wound repair by inhibiting inflammation, promoting angiogenesis, and cell proliferation.

A strategy of functional crosslinking acellular matrix in blood-contacting implantable devices with recombinant humanized collagen type III (rhCOLIII)

Abstract: A large number of blood contacting implantable devices are used worldwide annually. Acellular matrix (AM), as one of the blood-contacting materials, has achieved a great success, since it remains the structures, components and certain functions of extracellular matrix. However, AM often fails during the period of service owing to non-ideal anticoagulation, severe inflammatory responses and poor mechanical properties. Herein, we specially prepared a newly designed tailored recombinant humanized collagen type III (rhCOLIII) that effectively removed the binding site to platelets while retaining cytocompatibility. In this study, a radical-polymerization-crosslinked decellularized porcine pericardium (DPP) with rhCOLIII and glycidyl methacrylate (GMA) through one-pot method was designed as artificial heart valves. Due to the introduction of rhCOLIII, the anticoagulation properties were dramatically improved with fewer platelets adhesion and less thrombogenesis. The mechanical properties of the novel heart valve (rhCOLIII/GMA-DPP) were significantly enhanced through radical polymerization crosslinking. Furthermore, experiments in vivo and vitro showed the inflammatory responses were moderately reduced. In conclusion, this study provides a simple strategy for functional crosslinking AM in blood-contacting implantable devices and shows possibilities for real application.

Pathogenic and Potential Therapeutic Roles of Exosomes Derived From Immune Cells in Liver Diseases

Abstract: Liver diseases, such as viral hepatitis, alcoholic hepatitis and cirrhosis, nonalcoholic steatohepatitis, and hepatocellular carcinoma place a heavy burden on many patients worldwide. However, the treatment of many liver diseases is currently insufficient, and the treatment may be associated with strong side effects. Therapies for liver diseases targeting the molecular and cellular levels that minimize adverse reactions and maximize therapeutic effects are in high demand. Immune cells are intimately involved in the occurrence, development, and prognosis of liver diseases. The immune response in the liver can be suppressed, leading to tolerance in homeostasis. When infection or tissue damage occurs, immunity in the liver is activated rapidly. As small membrane vesicles derived from diverse cells, exosomes carry multiple cargoes to exert their regulatory effects on recipient cells under physiological or pathological conditions. Exosomes from different immune cells exert different effects on liver diseases. This review describes the biology of exosomes and focuses on the effects of exosomes from different immune cells on pathogenesis, diagnosis, and prognosis and their therapeutic potential in liver diseases.

A bioprosthetic heart valve material prepared by copolymerization of 2-Amino-4-pentanoic acid modified pericardium and N, N-Dimethylacrylamide

Abstract: Bioprosthetic heart valve thrombosis (BHVT) is no longer considered a rare clinical entity in recent years and could cause valve motion abnormalities, which requires reoperation. Currently reported modifications of bioprosthetic heart valves (BHVs) mainly focused on improving the anti-calcification property. However, it was hard to improve their anti-thrombogenicity and crosslinking efficiency at the same time. Here we reported a method that combines improved hemocompatibility , crosslinking efficiency, cytocompatibility, and anti-calcification property for BHVs. Porcine pericardia (PPs) and 2-amino-4-pentanoic acid (APA) were first co-crosslinked with glutaraldehyde to introduce allyl moieties to the PPs, then poly(N, N-dimethylacrylamide) (PDMAA) was covalently immobilized on PPs through radical polymerization . In vitro and in vivo studies demonstrated that the structural stability of PDMAA modified PPs was much superior than that of traditional glutaraldehyde crosslinked PPs (GA). The PDMAA modified PPs exhibited enhanced antithrombogenic performance with a 75% decrease of platelet adhesion compared with GA. Moreover, the calcium content accumulated on the modified PPs after 90-day rat subcutaneous implantation decreased 93.5% compared with that on GA. The PDMAA modified PPs may alleviate BHVT and calcification, offering a potential option for BHVs fabrication in the future. • A method for BHVs by copolymerization of functional monomer was constructed. • GA-PDMAA was demonstrated to exhibit improved antithrombogenic performance. • The calcification degree significantly decreased in GA-PDMAA compared to GA.

Development of Innovative Biomaterials and Devices for the Treatment of Cardiovascular Diseases (Adv. Mater. 46/2022)

Abstract: Cardiovascular Biomaterials and Devices In article number 2201971, Yunbing Wang and co-workers provide an overview of the challenges and research frontiers of innovative biomaterials and devices for the treatment of cardiovascular diseases, and their future development directions are discussed. With the development and improved performance of new cardiovascular biomaterials and devices, more advanced treatment options will be available to bring new hope to the cardiovascular patients.

Targeting keystone species helps restore the dysbiosis of butyrate‐producing bacteria in nonalcoholic fatty liver disease

Abstract: The dysbiosis of the gut microbiome is one of the pathogenic factors of nonalcoholic fatty liver disease (NAFLD) and also affects the treatment and intervention of NAFLD. Among gut microbiomes, keystone species that regulate the integrity and stability of an ecological community have become the potential intervention targets for NAFLD. Here, we collected stool samples from 22 patients with nonalcoholic steatohepatitis (NASH), 25 obese patients, and 16 healthy individuals from New York for 16S rRNA gene sequencing. An algorithm was implemented to identify keystone species based on causal inference theories and dynamic intervention simulation. External validation was performed in an independent cohort from California. Eight keystone species in the gut of NAFLD, represented by Porphyromonas loveana, Alistipes indistinctus, and Dialister pneumosintes, were identified, which could efficiently restore the microbial composition of the NAFLD toward a normal gut microbiome with 92.3% recovery. These keystone species regulate intestinal amino acid metabolism and acid–base environment to promote the growth of the butyrate-producing Lachnospiraceae and Ruminococcaceae species that are significantly reduced in NAFLD patients. Our findings demonstrate the importance of keystone species in restoring the microbial composition toward a normal gut microbiome, suggesting a novel potential microbial treatment for NAFLD.

Functional non-glutaraldehyde treated porcine pericardium for anti-coagulation, anti-calcification, and endothelial proliferation bioprosthetic heart valves

Abstract: Abstract In the last decade, the number of transcatheter heart valve replacement for severe heart valve disease has increased exponentially. Although the bioprosthetic artificial heart valve (BHV) has similar fluid dynamics performance to the original heart valve compared with mechanical heart valve so that there is no need to take long-term anticoagulant drugs to prevent thromboembolism, transcatheter BHV replacement are still at risk for thrombosis during the first few months according to the clinical data. However, the use of antithrombotic drugs can also increase the risk of bleeding. Therefore, it is particularly important to improve the anticoagulant properties for the BHV itself. In this work, a kind of non-glutaraldehyde cross-linked BHV material with excellent antithrombotic ability has been prepared from carboxylated oxazolidine treated porcine pericardium (consisting of collagen, elastin and glycoprotein) with the further graft of the anticoagulant heparin sodium via hydrophilic modified chitosan. Along with the similar mechanical properties and collagen stability comparable to the glutaraldehyde cross-linked porcine pericardium (PP), these functional non-glutaraldehyde cross-linked PPs exhibit better biocompatibility, promoted endothelial proliferation and superior anti-calcification ability. More importantly, excellent anticoagulant activity can be observed in the hematological experiments in vivo and in vitro. In summary, these excellent performances make these functional non-glutaraldehyde cross-linked PPs great potentialities in the BHV applications. Graphical abstract

Yes-associated protein contributes to magnesium alloy-derivedinflammation in endothelial cells

Abstract: Abstract Magnesium alloy (Mg alloy) has attracted massive attention in the potential applications of cardiovascular stents because of its good biocompatibility and degradability. However, whether and how the Mg alloy induces inflammation in endothelial cells remains unclear. In the present work, we investigated the activation of Yes-associated protein (YAP) upon Mg alloy stimuli and unveiled the transcriptional function in Mg alloy-induced inflammation. Quantitative RT–PCR, western blotting and immunofluorescence staining showed that Mg alloy inhibited the Hippo pathway to facilitate nuclear shuttling and activation of YAP in human coronary artery endothelial cells (HCAECs). Chromatin immunoprecipitation followed sequencing was carried out to explore the transcriptional function of YAP in Mg alloy-derived inflammation. This led to the observation that nuclear YAP further bonded to the promoter region of inflammation transcription factors and co-transcription factors. This binding event activated their transcription and modified mRNA methylation of inflammation-related genes through regulating the expression of N6-methyladenosine modulators (METTL3, METTL14, FTO and WTAP). This then promoted inflammation-related gene expression and aggravated inflammation in HCAECs. In YAP deficiency cells, Mg alloy-induced inflammation was reduced. Collectively, our data suggest that YAP contributes to the Mg alloy-derived inflammation in HCAECs and may provide a potential therapeutic target that alleviates inflammation after Mg alloy stent implantation.

Arsenic trioxide activates yes-associated protein by lysophosphatidic acid metabolism to selectively induce apoptosis of vascular smooth muscle cells.

Abstract: Inhibition of vascular smooth muscle cells (VSMCs) proliferation without dysregulating endothelial cells (ECs) may provide an ideal therapy for in-stent restenosis. Due to its anti-proliferation effect on VSMCs and pro-endothelium effect, arsenic trioxide (ATO) has been used in a drug-eluting stent in a recent clinical trial. However, the underlying mechanism by which ATO achieves this effect has not been determined. In the present work, we showed that ATO induced apoptosis in VSMCs but not in ECs. Mechanistically, ATO achieved this through modulation of cellular metabolism to increase lysophosphatidic acid (LPA) in VSMCs, while LPA concentration was stable in ECs. The elevated LPA facilitated the nuclear accumulation and initiated the transcriptional function of Yes-associated protein (YAP) in VSMCs. YAP regulated the transcription of N6-Methyladenosine (m6A) modulators (Mettl14 and Wtap) to increase the m6A methylation levels of apoptosis-related genes to induce their high expression and exacerbate VSMCs apoptosis. On the other hand, YAP nuclear accumulation in ECs was not observed. Collectively, our data exhibited the molecular process involved in selective apoptosis of VSMCs induced by ATO.

A novel potential mechanism for the development of portal vein thrombosis in cirrhosis based on portal hemodynamics

Abstract: Marked changes in hemodynamics have been suggested to be a potential contributing factor to portal vein thrombosis (PVT) development. This study investigated the effect of portal hemodynamics based on the anatomical structure of the portal venous system on PVT development.The morphological features of portal venous system in patients with PVT and those without PVT subgroups were compared. In addition, idealized PV models were established to numerically evaluate the effect of the variation in the angulation of superior mesenteric vein (SMV) and splenic vein (SV) on the hemodynamics of portal venous system.The angle α (angulation of SMV and SV) in patients with PVT was lower than that in patients without PVT (p < 0.0001), which was the only independent risk factor (odds ratio (OR), 0.90 (95% CI 0.84-0.95); p < 0.0001) for the presence of PVT. With the change in angle α, the flow pattern of blood flow changed greatly, especially the helical flow. When α = 80°, helical flow only appeared at the local PV near the intersection of SMV and SV. When α = 120°, most regions were occupied by the helical flow. In addition, the h2 gradually increased with increasing α, when α = 80°, h2 = 12.6 m/s2; when α = 120°, h2 = 29.3 m/s2.The angulation of SV and SMV was closely associated with PVT development. Helical flow changed following the varying angulation of SV and SMV. Therefore, angulation of SV and SMV may help to identify high-risk cohorts for future PVT development earlier.

High Interleukin-8 Levels Associated With Decreased Survival in Patients With Cirrhosis Following Transjugular Intrahepatic Portosystemic Shunt

Abstract: Background Serum cytokines—reflecting systemic inflammation has been associated with the risk of decompensation and mortality in patients with cirrhosis. However, the role of systemic inflammation in patients with cirrhosis undergoing transjugular intrahepatic portosystemic shunt procedure remains unknown. Patients and Methods Patients with cirrhosis who received transjugular intrahepatic portosystemic shunt between June 2015 and September 2017 were included. Portal and hepatic venous blood samples were obtained intraoperatively; serum cytokine levels (IL-10, IL-17A, IL-1RA, IL-8, and CXCL10) were measured in 105 patients. Associations with survival and other outcomes during long-term follow-up (median: 1,564 days) were assessed using logistic regression. Results IL-17A and CXCL10 levels were higher in the portal than in the hepatic veins, whereas IL-1RA levels were higher in the hepatic than in the portal veins. However, IL-8 or IL-10 levels between hepatic and portal veins showed no differences. Multivariate analysis demonstrated that Child–Pugh scores (P = 0.017, HR: 1.484, 95% CI: 1.072–2.055) and IL-8 level in hepatic veins (P < 0.001, HR: 1.043, 95% CI: 1.019–1.068) were independent predictors for mortality during long-term follow-up, with an optimal cut-off of 5.87 pg/ml for IL-8 in hepatic veins. Patients with hepatic IL-8 levels < 5.87 pg/ml had significantly higher cumulative survival rates (98.4 vs. 72.9% at 1 year, 98.4 vs. 65.3% at 2 years, 96.7 vs. 60.3% at 3 years, 94.2 vs. 60.3% at 4 years; P < 0.0001). Conclusions IL-8 levels in hepatic veins may reflect liver cirrhosis severity. Elevated IL-8 levels suggest shorter survival in patients receiving TIPS.