Serum Hyaluronic Acid Research Articles

Associations between serum biomarkers of cartilage metabolism and serum hyaluronic acid, with risk factors, pain categories, and disease severity in knee osteoarthritis: a pilot study

BackgroundSpecific serum biomarkers of cartilage metabolism such as cartilage oligomeric matrix protein (sCOMP) and procollagen type II C-terminal propeptide (sPIICP) as well as hyaluronan (sHA), a biomarker of synovitis, have been implicated in the pathophysiology of knee osteoarthritis (OA). However, the associations of these biomarkers with the severity of the disease and OA risk factors, including age and obesity remain inconclusive. This analysis examines the associations between these serum biomarkers and the radiographic severity of OA and knee pain, as wells as obesity, the age and gender of the participants, and other OA risk factors.MethodsFrom 44 patients with early knee OA and 130 patients with late knee OA we analyzed the radiographic severity of the disease using the Kellgren and Lawrence (KL) grading system. Moreover, 38 overweight healthy individuals were used as a control group. Specific information was collected from all participants during their recruitment. The levels of the three serum biomarkers were quantified using commercially available ELISA kits. Serum biomarkers were analyzed for associations with the average KL scores and pain in both knees, as well as with specific OA risk factors.ResultsThe levels of sCOMP were elevated in patients with severe late OA and knee pain and correlated weakly with OA severity. A weakly correlation of sHA levels and OA severity OA was observed. We demonstrated that only sPIICP levels were markedly decreased in patients with late knee OA suggesting the alterations of cartilage metabolism in this arthritic disease. Moreover, we found that sPIICP has the strongest correlation with obesity and the severity of OA, as well as with the knee pain at rest and during walking regardless of the severity of the disease. ROC analysis showed that the area under the ROC curve (AUC) was 0.980 (95% CI: 0.945–0.995; p < 0.0001), suggesting high diagnostic accuracy of sPIICP. Interestingly, gender and age had also an effect on the levels of sPIICP.ConclusionThis study revealed the potential of serum PIICP to be used as a biomarker to monitor the progression of knee OA, however, further studies are warranted to elucidate its clinical implication.

Increased Levels of CHI3L1 and HA Are Associated With Higher Occurrence of Liver Damage in Patients With Obstructive Sleep Apnea.

BackgroundObstructive sleep apnea-hypopnea syndrome (OSA) may cause liver fibrosis, and liver fibrosis serum biomarkers plays an important role on the diagnosis of liver fibrosis. In addition, this study aimed to observe the changes of 4 serum markers and Chitinase 3-like protein 1 (CHII3L1) levels in OSA patients with different disease severity and explore their interactions. And then, we examined whether intermittent hypoxia (IH) exposure can activate hepatic stellate cell.Methods74 OSA patients in Second Xiangya hospital from January 2021 to October 2021 was selected and categorized into mild, moderate, and severe groups according to AHI. In addition, 20 subjects were selected as the control group. Serum levels of liver fibrosis markers were determined by electrochemiluminescence immunoassay. Hepatic stellate cells were exposed to intermittent IH or normoxia (RA). Results were analyzed using the SPSS software.ResultsThere was a significant increase in serum hyaluronic acid (HA), collagen type IV (CIV) and CHI3L1 levels in OSA patients compared with control group. Specifically, serum liver fibrosis markers HA, CIV and CHI3L1 levels were positively correlated with apnea-hypopnea index (AHI), but negatively correlated with the lowest saturation oxygen (LSaO2) respectively. The LX-2 cells (human hepatic stellate cell line) exposed to IH showed significant increases in fibrotic protein expression.ConclusionOSA might either directly or indirectly trigger or exacerbate liver fibrosis, possibly via IH-related pathways.

Interaction between CD44 and highly condensed hyaluronic acid through crosslinking with proteins

Proteins and nucleic acids derived from bioresources have become a novel medical modality. However, the intrinsic features of proteins, such as their high molecular weight and polarity, impede their passage through the cell membrane. In this study, to deliver proteins to cancer cells, we prepared conjugates consisting of bovine serum albumin (BSA) and hyaluronic acid (HA). These conjugates contained multiple BSA and HA molecules and adopted a highly condensed structure by crosslinking through BSA. When the interaction between the HA-BSA conjugates and recombinant CD44 (rCD44) was examined using a quartz crystal microbalance, the conjugates induced a larger decrease of frequency change than HA. CT26 cells treated with FITC-labeled HA-BSA conjugates showed high fluorescence intensity. The uptake of the conjugates decreased upon adding excess HA. Therefore, the conjugates and nanoparticles with densely packed HA structures could be a potent and effective platform for delivering proteins to cancer tissues.

Heme Oxygenase-1 Inhibits the Proliferation of Hepatic Stellate Cells by Activating PPARγ and Suppressing NF-κB.

Background Hepatic stellate cells (HSCs) are reported to play significant roles in the development of liver fibrosis. Heme oxygenase-1 (HO-1) is a key rate-limiting enzyme, which could decrease collagen synthesis and liver damage. Nevertheless, it was yet elusive towards the function and mechanism of HO-1. Methods An HO-1 inducer Hemin or an HO-1 inhibitor ZnPP-IX was used to treat the activated HSC-T6, respectively. MTT assay was adopted to detect cell proliferation. Immunocytochemical staining was employed to test the levels of alpha-smooth muscle actin (α-SMA), peroxisome proliferator-activated receptor-γ (PPARγ), and nuclear factor-kappa B (NF-kappa B) levels in HSC-T6. HO-1, PPARγ, and NF-κB expression levels were measured by qRT-PCR and Western blotting. ELISA was then used to detect the levels of transforming growth factor- (TGF-) beta 1 (TGF-β1), interleukin-6 (IL-6), serum hyaluronic acid (HA), and serum type III procollagen aminopeptide (PIIIP). Results HSC-T6 proliferation was inhibited in Hemin-treated HSCs. The levels of α-SMA, HA, and PIIIP and the production of ECM were lower in Hemin-treated HSCs, whereas those could be rescued by ZnPP-IX. NF-κB activation was decreased, but PPARγ expression was increased after HO-1 upregulation. Furthermore, the levels of TGF-β1 and IL-6, which were downstream of activated NF-κB in HSC-T6, were reduced. The PPAR-specific inhibitor GW9662 could block those mentioned effects. Conclusions Our data demonstrated that HO-1 induction could inhibit HSC proliferation and activation by regulating PPARγ expression and NF-κB activation directly or indirectly, which makes it a promising therapeutic target for liver fibrosis.

Hyaluronic acid plasma levels during high versus low tidal volume ventilation in a porcine sepsis model.

BackgroundShedding of the endothelial glycocalyx can be observed regularly during sepsis. Moreover, sepsis may be associated with acute respiratory distress syndrome (ARDS), which requires lung protective ventilation with the two cornerstones of application of low tidal volume and positive end-expiratory pressure. This study investigated the effect of a lung protective ventilation on the integrity of the endothelial glycocalyx in comparison to a high tidal volume ventilation mode in a porcine model of sepsis-induced ARDS.MethodsAfter approval by the State and Institutional Animal Care Committee, 20 male pigs were anesthetized and received a continuous infusion of lipopolysaccharide to induce septic shock. The animals were randomly assigned to either low tidal volume ventilation, high tidal volume ventilation, or no-LPS-group groups and observed for 6 h. In addition to the gas exchange parameters and hematologic analyses, the serum hyaluronic acid concentrations were determined from central venous blood and from pre- and postpulmonary and pre- and postcerebral circulation. Post-mortem analysis included histopathological evaluation and determination of the pulmonary and cerebral wet-to-dry ratios.ResultsBoth sepsis groups developed ARDS within 6 h of the experiment and showed significantly increased serum levels of hyaluronic acid in comparison to the no-LPS-group. No significant differences in the hyaluronic acid concentrations were detected before and after pulmonary and cerebral circulation. There was also no significant difference in the serum hyaluronic acid concentrations between the two sepsis groups. Post-mortem analysis showed no significant difference between the two sepsis groups.ConclusionIn a porcine model of septic shock and ARDS, the serum hyaluronic acid levels were significantly elevated in both sepsis groups in comparison to the no-LPS-group. Intergroup comparison between lung protective ventilated and high tidal ventilated animals revealed no significant differences in the serum hyaluronic acid levels.

Role of serum hyaluronic acid in predicting necroinflammatory activity of the nonalcoholic fatty liver disease.

Background and Aim:Hyaluronic acid (HA), a fundamental component of the extracellular matrix, is associated with chronic liver diseases. The aim of this study was to investigate quantitative HA measurement as a noninvasive marker for steatosis and fibrosis staging in nonalcoholic fatty liver disease (NAFLD) with biopsy evidence.Materials and Methods:In this study, 52 NAFLD patients with biopsy evidence and who met the inclusion criteria were included. Hepatic enzyme levels, HA levels, and other laboratory findings were examined. In addition, the degree of steatosis was determined via computed tomography (CT).Results:According to the degree of steatosis, HA levels were 29.17±22.66, 39.85±60.28, and 32.05±19.40, respectively, and no significant difference was found between the groups (p=0.584). In addition, HA levels were not found to be significant according to the degrees of steatohepatitis (p=0.860). However, a statistically significant relationship was found between steatosis levels detected by CT and biopsy (p<0.01).Conclusion:Serum HA level, other biochemical parameters, and steatosis severity measurement via CT did not appear to have any diagnostic value for nonalcoholic steatohepatitis. In this context, novel markers that may be useful for NAFLD diagnosis and severity assessment in risky individuals should be investigated.

Meta-analysis of efficacy and safety of Liuwei Wuling Tablets combined with conventional drugs in treatment of liver fibrosis and cirrhosis in chronic hepatitis B

The present study evaluated the clinical efficacy and safety of Liuwei Wuling Tablets combined with conventional drugs for the treatment of liver fibrosis and cirrhosis in chronic hepatitis B. CNKI, Wanfang, VIP, CBM, PubMed, EMbase and Cochrane Library were searched for the relevant randomized controlled trials(RCTs) published from database inception to February 2021. All the retrieved papers were independently screened, extracted and evaluated by two researchers, followed by Meta-analysis by Review Manager 5.4. Finally, 18 RCTs were included, involving 2 168 patients(1 106 in the treatment group and 1 062 in the control group). The Meta-analysis results showed that compared with conventional drugs alone, Liuwei Wuling Tablets combined with conventional drugs could increase the effective rate of clinical treatment by reducing serum hyaluronic acid(HA), laminin(LN), procollagen type Ⅲ(PCⅢ), and type Ⅳ collagen(Ⅳ-C) to improve liver function, decreasing the levels of total bilirubin(TBiL), alanine amino-transferase(ALT), and aspartate aminotransferase(AST), and improving the negative conversion ratio of hepatitis B virus(HBV) DNA. In terms of safety, there were no serious adverse reactions in the treatment group and the control group. The results showed that Liuwei Wuling Tablets combined with antiviral or other conventional liver-protecting drugs could improve liver function, treat liver cirrhosis, and reduce liver fibrosis with high safety. However, due to the influence of literature quality and quantity, multi-center and high-quality RCTs with large sample size are needed for verification.

Telmisartan relieves liver fibrosis and portal hypertension by improving vascular remodeling and sinusoidal dysfunction

BackgroundsTelmisartan(TEL) has demonstrated anti-fibrotic and blood pressure lowering effect in various diseases. In this study, we aimed to explore the beneficial effects of TEL on portal hypertension(PHT). MethodsTwo models of cirrhosis-induced PHT were involved including carbon tetrachloride injection(CCl4) and bile duct ligation(BDL). Rats were orally gavaged with TEL for 4 weeks. After that, the portal pressure(PP) was determined, and liver and mesenteric tissue specimens were collected to evaluate inflammatory response, liver fibrosis, vascular remodeling, angiogenesis, etc. ResultsIn CCl4 PHT models, TEL decreased PP significantly from 12.79 ± 2.92 to 6.91 ± 1.19 mmHg(p < 0.05). In inflammatory response, hepatic expressions of interleukin(IL)-6, lipopolysaccharide(LPS), and tumor necrosis factor-α(TNF-α) were significantly decreased after TEL treatment. Moreover, in the liver fibrotic area, the expressions of α-smooth muscle actin(α-SMA), collagen1a1(Col1a1), desmin, transforming growth factor-β(TGF-β), and hydroxyproline, and serum hyaluronic acid were significantly decreased after TEL treatment. Additionally, the expressions of von Willebrand factor(vWF), vascular endothelial growth factor(VEGF) and platelet-derived growth factor-β(PDGF-β), matrix metallopeptidase(MMP)-2, and MMP-9 were ameliorated in liver sinusoid, while the expressions of MMP-2 and vWF were reduced in mesenteric arteries after TEL treatment. Meanwhile, TEL treatment up-regulated the hepatic expressions of an anti-fibrotic factor Krüppel-like factor-4(KLF-4) and its downstream endothelial nitric oxide synthase(eNOS) in rats with PHT. The performance of TEL in BDL model was similar but slightly weaker. ConclusionsTEL ameliorated the cirrhosis-induced PHT by reducing liver fibrosis, inflammation responses, angiogenesis, and vascular remodeling. Collectively, KLF-4 and eNOS were the possible molecular targets for the management of cirrhosis-associated PHT.

Enhanced Liver Fibrosis Score as a Biomarker for Vascular Damage Assessment in Patients with Takayasu Arteritis-A Pilot Study.

Takayasu Arteritis (TA) is characterized by granulomatous panarteritis, vessel wall fibrosis, and irreversible vascular impairment. The aim of this study is to explore the usefulness of the Enhanced Liver Fibrosis score (ELF), procollagen-III aminoterminal propeptide (PIIINP), tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), and hyaluronic acid (HA) in assessing vascular damage in TA patients. ELF, PIIINP, TIMP-1, and HA were measured in 24 TA patients, and the results were correlated with the clinical damage indexes (VDI and TADS), an imaging damage score (CARDS), and disease activity scores (NIH and ITAS2010). A mean ELF score 8.42 (±1.12) and values higher than 7.7 (cut-off for liver fibrosis) in 21/24 (87.5%) of patients were detected. The VDI and TADS correlated significantly to ELF (p < 0.01). Additionally, a strong association across ELF and CARDS (p < 0.0001), PIIINP and CARDS (p < 0.001), and HA and CARDS (p < 0.001) was observed. No correlations of the tested biomarkers with inflammatory parameters, NIH, and ITAS2010 scores were found. To our knowledge, this is the first study that suggests the association of the serum biomarkers PIIINP, HA, and ELF score with damage but not with disease activity in TA patients. The ELF score and PIIINP may be useful biomarkers reflecting an ongoing fibrotic process and quantifying vascular damage.

Treating Full Depth Cartilage Defects with Intraosseous Infiltration of Plasma Rich in Growth Factors: An Experimental Study in Rabbits.

Intraarticular (IA) administration of platelet-rich plasma (PRP) has been proposed as a new strategy to halt osteoarthritis (OA) progression. In patients with severe OA, its potential is limited because it is unable to reach the subchondral bone, so a new strategy is needed, and intraosseous (IO) infiltration has been suggested. The purpose is to assess the impact of IA together with IO infiltration of plasma rich in growth factors (PRGF) in serum hyaluronic acid (HA) and type II collagen cleavage neoepitope (C2C) levels. A total of 32 rabbits were included in the study and randomly divided into 2 groups: control and treatment. A 4-mm chondral defect was created in the medial femoral condyle and IA followed by IO infiltration were performed. Serum C2C and HA levels were measured using enzyme-linked immunosorbent assay (ELISA) tests before infiltration and 28, 56, and 84 days post-infiltration. Significant lower C2C serum levels were obtained in treatment group (IA + IO infiltration of PRGF) at 84 days post-infiltration than in control group (IA infiltration of PRGF + IO infiltration of saline solution), while no significant differences between groups were reported at any other study times. Regarding HA, at 56 days post-infiltration, greater significant levels were seen in the treatment group. However, at 84 days post-infiltration, no significant differences were obtained, although lower levels were reported in the treatment group. Despite inconclusive, the results suggest that the combination of IA and IO infiltration with PRGF may enhance cartilage and subchondral bone regeneration, but further studies are needed.

Intriguing findings of liver fibrosis following COVID-19

BackgroundStudies on a new coronavirus disease (COVID-19) show the elevation of liver enzymes and liver fibrosis index (FIB-4) independently on pre-existing liver diseases. It points to increased liver fibrogenesis during acute COVID-19 with possible long-term consequences. This study aimed to assess liver fibrosis in COVID-19 patients by serum hyaluronic acid (HA) and FIB-4.MethodsThe study included the acute COVID-19 group (66 patients, 50% females, mean age 58.3 ± 14.6), the post-COVID group (58 patients in 3–6 months after the recovery, 47% females, mean age 41.2 ± 13.4), and a control group (17 people, 47% females, mean age 42.8 ± 11.0). Ultrasound elastography was performed in the post-COVID and control groups.ResultsSixty-five percent of the acute COVID-19 group had increased FIB-4 (> 1.45), and 38% of patients had FIB-4 ≥ 3.25. After matching by demographics, 52% of acute COVID-19 and 5% of the post-COVID group had FIB-4 > 1.45, and 29% and 2% of patients had FIB-4 ≥ 3.25, respectively. Increased serum HA (≥ 75 ng/ml) was observed in 54% of the acute COVID-19 and 15% of the post-COVID group. In the acute COVID-19 group, HA positively correlated with FIB-4, AST, ALT, LDH, IL-6, and ferritin and negatively with blood oxygen saturation. In the post-COVID group, HA did not correlate with FIB-4, but it was positively associated with higher liver stiffness and ALT.ConclusionMore than half of acute COVID-19 patients had increased serum HA and FIB-4 related to liver function tests, inflammatory markers, and blood oxygen saturation. It provides evidence for the induction of liver fibrosis by multiple factors during acute COVID-19. Findings also indicate possible liver fibrosis in about 5% of the post-COVID group.

Evaluation of the Role of Hyaluronic Acid as a Potential Marker for Diagnosis of Non-Alcoholic Fatty Liver Disease

Abstract Background Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease worldwide, ranging from simple steatosis and nonalcoholic steatohepatitis (NASH) to liver cirrhosis, with its complications including hepatocellular carcinoma (HCC). Aim of the Work to evaluate the efficacy and reliability of Hyaluronic Acid as a potential noninvasive biomarker for diagnosis and prognosis of NAFLD and to compare it with the traditional noninvasive techniques and if it can replace liver biopsy. Patients and Methods This cross-sectional study was conducted on 63 subjects from the Gastroenterology and Hepatology Department of Ain Shams University Hospital. They were divided into three different groups as following: a healthy control group, fatty liver and nonalcoholic steatohepatitis (NASH). All patients and controls were subjected to routine laboratory tests and serum Hyaluronic acid test. Results There were high statistical significant differences between groups as regard INR. Regarding to liver functions, there was a high statistical significant difference between groups as regard AST and ALT ,Bilirubin and Albumin.. Comparison between groups regarding to RBS, there was high statistical significant difference between groups as regard RBS. Comparison between groups regarding to lipid profile, there was high statistical significant difference between groups as regard LDL and cholesterol. Regarding to APRI and Fib4, there was high statistical significant difference between groups as regard APRI and Fib4. Regarding to H.A, there was high statistical significant difference between groups as regard H.A. The study shows that there is non-significant correlation between either APRI or Fib4 and H.A in fatty liver, and there is also nonsignificant correlation either APRI or Fib4 and H.A in NASH. Conclusion Hyaluronic Acid can be reliably used as an accurate and specific noninvasive biomarker for the diagnosis of Nonalcoholic fatty Liver Disease and staging of the severity of disease compared with the traditional known noninvasive scores

Неінвазивна діагностика фіброзу печінки у хворих із неалкогольною жировою хворобою печінки

Актуальність. Неалкогольна жирова хвороба печінки (НАЖХП) — хронічна дифузна патологія печінки, що пов’язана з інсулінорезистентністю та метаболічними порушеннями, серед яких ожиріння, цукровий діабет 2 типу та дисліпідемія. НАЖХП охоплює простий стеатоз, який має доброякісний перебіг, неалкогольний стеатогепатит, що може прогресувати до цирозу та гепатоцелюлярної карциноми. Морфологічне дослідження печінки залишається золотим стандартом для оцінки ступеня стеатозу, печінкового запалення і фіброзу, однак все більший інтерес останнім часом викликають неінвазивні методи, серед яких оцінка різних індексів, заснованих на сироваткових маркерах. Мета. Оцінка показників діагностичної точності сироваткових маркерів та неінвазивних лабораторних індексів у визначенні морфологічних змін печінки у хворих на НАЖХП. Матеріали та методи. У дослідження включені 60 пацієнтів із НАЖХП, які проходили обстеження й лікування у відділенні захворювань печінки та підшлункової залози ДУ «Інститут гастроентерології НАМН України». Серед досліджених 26 (42,3 %) чоловіків та 34 (56,7 %) жінки, середнім віком (37,1 ± 12,4) та (44,3 ± 7,3) року відповідно. Усім пацієнтам була проведена черезшкірна пункційна трепан-біопсія печінки з подальшим морфологічним дослідженням пунктату; виконано визначення вмісту гіалуронової кислоти, a2-макроглобуліну, аполіпопротеїну А1, фібронектину, гаптоглобіну в сироватці крові, був проведений розрахунок неінвазивних маркерів фіброзу печінки: AAR, APRI, FIB-4. Результати. У хворих на НАЖХП встановлено високу діагностичну точність сироваткових маркерів фіброзу як при розмежуванні різних стадій фіброзу, так і при виключенні саме наявності фіброзу. Висновки. Визначення сироваткових маркерів має значення для вирішення питання про необхідність медикаментозного лікування та його тактику, а відповідність неінвазивних маркерів золотому стандарту — морфологічному дослідженню дозволяє уникати біопсії печінки як методу з потенційно можливими ускладненнями внаслідок своєї інвазивності.

Synthesis of a Lubricant to Mimic the Biorheological Behavior of Osteoarthritic and Revision Synovial Fluid

The rheological properties of synovial fluid (SF) are essential for the friction behavior and wear performance of total joint replacements. Standardized in vitro wear tests for endoprosthesis recommend diluted calf serum, which exhibits substantial different rheological properties compared to SF. Therefore, the in vitro test conditions do not mimic the in vivo conditions. SF samples from osteoarthritis knee patients and patients undergoing knee endoprosthesis revision surgery were compared biochemically and rheologically. The flow properties of SF samples were compared to synthetic fluid constituents, such as bovine serum albumin (BSA) and hyaluronic acid (HA). Interestingly, HA was identified as a significant contributor to shear-thinning. Using the acquired data and mathematical modelling, the flow behavior of human SF was modelled reliably by an adapted adjustment of biorelevant fluid components. Friction tests in a hard/soft bearing (ceramic/UHMWPE) demonstrated that, in contrast to serum, the synthetic model fluids generate a more realistic friction condition. The developed model for an SF mimicking lubricant is recommended for in vitro wear tests of endoprostheses. Furthermore, the results highlight that simulator tests should be performed with a modified lubricant considering an addition of HA for clinically relevant lubrication conditions.

Transcriptomics Identify Thrombospondin-2 as a Biomarker for NASH and Advanced Liver Fibrosis.

Background and AimsNAFLD is the most common liver disease worldwide. NASH, the progressive form of NAFLD, and advanced fibrosis are associated with poor outcomes. We searched for their noninvasive biomarkers.Approach and ResultsGlobal RNA sequencing of liver tissue from 98 patients with biopsy‐proven NAFLD was performed. Unsupervised hierarchical clustering well distinguished NASH from nonalcoholic fatty liver (NAFL), and patients with NASH exhibited molecular abnormalities reflecting their pathological features. Transcriptomic analysis identified proteins up‐regulated in NASH and/or advanced fibrosis (stage F3‐F4), including matricellular glycoprotein thrombospondin‐2 (TSP‐2), encoded by the thrombospondin 2 (THBS2) gene. The intrahepatic THBS2 expression level showed the highest areas under the receiver operating characteristic curves (AUROCs) of 0.915 and 0.957 for diagnosing NASH and advanced fibrosis, respectively. THBS2 positively correlated with inflammation and ballooning according to NAFLD activity score, serum aspartate aminotransferase and hyaluronic acid (HA) levels, and NAFLD Fibrosis Score (NFS). THBS2 was associated with extracellular matrix and collagen biosynthesis, platelet activation, caspase‐mediated cleavage of cytoskeletal proteins, and immune cell infiltration. Serum TSP‐2 expression was measured in 213 patients with biopsy‐proven NAFLD, was significantly higher in NASH than in NAFL, and increased parallel to fibrosis stage. The AUROCs for predicting NASH and advanced fibrosis were 0.776 and 0.856, respectively, which were comparable to Fibrosis‐4 index, serum HA level, and NFS in advanced fibrosis diagnosis. Serum TSP‐2 level and platelet count were independent predictors of NASH and advanced fibrosis. Serum TSP‐2 levels could stratify patients with NAFLD according to the risk of hepatic complications, including liver cancer and decompensated cirrhotic events.ConclusionsTSP‐2 may be a useful biomarker for NASH and advanced fibrosis diagnosis in patients with NAFLD.

25877 Efficacy evaluation of a topical hyaluronic acid serum

Background: Hyaluronic acid (HA) is an anionic nonsulfated glycosaminoglycan found in the extracellular matrix in the basal layer of the epidermis where proliferating keratinocytes are present. HA acts as a biologic humectant thus retaining water in the skin making it useful as a topical moisturizing ingredient. The goal of the research was to evaluate the ability of a HA facial serum to deliver skin benefits by promoting skin plumpness and hydration while minimizing fine lines/wrinkles and improving the overall global assessment of facial skin appearance.

Effect of Different Solvent Extracts of Amygdalus mongolica on Liver Fibrosis Rat Models Induced by Carbon Tetrachloride and Its Mechanisms

To investigate the effects and possible mechanisms of different polarity positions of Amygdalus mongolica on carbon tetrachloride to hepatic fibrosis rats. Male SD rats were divided into 7 groups with 10 in each group. The rats were divided into model group, silymarin group (0.05 g/kg), positive drug group and Amygdalus mongolica petroleum ether, ethyl acetate, n-butanol and aqueous extract group. The rats in the same group were not given carbon tetrachloride as normal control group. After 8 weeks of treatment, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) activity and malondialdehyde (MDA), superoxide dismutase (SOD), hyaluronic acid (HA), laminin (LN), type Ⅲ collagen (PC-Ⅲ) and type Ⅳ collagen (Col-Ⅳ) content were measureed, and the liver index and spleen index were calculated; The contents of MDA, SOD and Hydroxyproline(HYP) and the expressions of transforming growth factor β1 protein (TGF-β1), mothers against decapentaplegic homolog 3 (Smad3) and Smad7 mRNA in liver tissues were also measured. Compared with the model group, the body mass of the rats in various polar parts of Amygdalus mongolica significantly increased (P<0.05), MDA in serum and tissues significantly decreased (P<0.05), SOD in serum significantly increased (P<0.05), and liver index of the rats in petroleum ether and water parts significantly decreased (P<0.05). The results of pathological examination showed that the liver fibrosis of the rats in each part of the drug group was significantly improved. Amygdalus mongolica petroleum ether part and n-butanol part could significantly decrease in the serum AST, ALP, HA, PC-Ⅲ content (P<0.05), HYP, TGF-β1 and Smad3 levels in the organization (P<0.05). The n-butanol position of Amygdalus mongolica could significantly reduce the serum ALT level (P<0.05). Amygdalus mongolica herbs petroleum ether, n-butanol extract has improved markedly effect to liver fibrosis, which is the preferred active site for protection of liver fibrosis and its mechanism may be through adjusting abnormal collagen synthesis and TGF-β1 / Smad signaling pathways to work.

Protectin conjugates in tissue regeneration 1 restores lipopolysaccharide-induced pulmonary endothelial glycocalyx loss via ALX/SIRT1/NF-kappa B axis

BackgroundEndothelial glycocalyx loss is integral to increased pulmonary vascular permeability in sepsis-related acute lung injury. Protectin conjugates in tissue regeneration 1 (PCTR1) is a novel macrophage-derived lipid mediator exhibiting potential anti-inflammatory and pro-resolving benefits.MethodsPCTR1 was administrated intraperitoneally with 100 ng/mouse after lipopolysaccharide (LPS) challenged. Survival rate and lung function were used to evaluate the protective effects of PCTR1. Lung inflammation response was observed by morphology and inflammatory cytokines level. Endothelial glycocalyx and its related key enzymes were measured by immunofluorescence, ELISA, and Western blot. Afterward, related-pathways inhibitors were used to identify the mechanism of endothelial glycocalyx response to PCTR1 in mice and human umbilical vein endothelial cells (HUVECs) after LPS administration.ResultsIn vivo, we show that PCTR1 protects mice against lipopolysaccharide (LPS)-induced sepsis, as shown by enhanced the survival and pulmonary function, decreased the inflammatory response in lungs and peripheral levels of inflammatory cytokines such as tumor necrosis factor-α, interleukin-6, and interleukin-1β. Moreover, PCTR1 restored lung vascular glycocalyx and reduced serum heparin sulphate (HS), syndecan-1 (SDC-1), and hyaluronic acid (HA) levels. Furthermore, we found that PCTR1 downregulated heparanase (HPA) expression to inhibit glycocalyx degradation and upregulated exostosin-1 (EXT-1) protein expression to promote glycocalyx reconstitution. Besides, we observed that BAY11-7082 blocked glycocalyx loss induced by LPS in vivo and in vitro, and BOC-2 (ALX antagonist) or EX527 (SIRT1 inhibitor) abolished the restoration of HS in response to PCTR1.ConclusionPCTR1 protects endothelial glycocalyx via ALX receptor by regulating SIRT1/NF-κB pathway, suggesting PCTR1 may be a significant therapeutic target for sepsis-related acute lung injury.

Influence of cytokines, circulating markers and growth factors on liver regeneration and post-hepatectomy liver failure: a systematic review and meta-analysis

The pathophysiology of post-hepatectomy liver failure is not entirely understood but is rooted in the disruption of normal hepatocyte regeneration and homeostasis. Current investigations of post-hepatectomy liver failure and regeneration are focused on evaluation of circulating hepatic function parameters (transaminases, cholestasis, and coagulation parameters), volumetry and hepatic hemodynamics. However, identification of biochemical factors associated with regeneration and post hepatectomy liver failure is crucial for understanding the pathophysiology and identification of patients at risk. The objective of the present systematic review was to identify circulating factors associated with liver regeneration and post hepatectomy liver failure in patients undergoing hepatectomy. The quantitative analysis was intended if studies provided sufficient data. Electronic databases (MEDLINE via PubMed, Web of Knowledge, Cochrane Library and WHO International Clinical Trials Registry Platform) were searched for publications on cell signaling factors in liver regeneration and post-hepatectomy liver failure following liver resection in clinical setting. No date restriction was given. No language restriction was used. Studies were assessed using MINORS. This study was registered at PROSPERO (CRD42020165384) prior to data extraction. In total 1953 publications were evaluated for titles and abstracts after exclusion of duplicates. Full texts of 167 studies were further evaluated for inclusion. 26 articles were included in the review and 6 publications were included in the meta-analyses. High levels of serum hyaluronic acid even preoperatively are associated with PHLF but especially increased levels early after resection are predictive of PHLF with high sensitivity and specificity. Postoperative elevation of HA to levels between 100 and 500 ng/ml is increased the risk for PHLF ([OR] = 246.28, 95% [CI]: 11.82 to 5131.83; p = 0.0004) Inteleukin-6 levels show contradicting result in association with organ dysfunction. HGF positively correlates with liver regeneration. Overall, due to heterogeneity, scarcity, observational study design and largely retrospective analysis, the certainty of evidence, assessed with GRADE, is very low. High levels of serum hyaluronic acid show a strong association with PHLF and increased levels after resection are predictive of PHLF with high sensitivity and specificity, even on POD1. Interleukin-6 levels need to be studied further due to contradictive results in association with organ dysfunction. For HGF, no quantitative analysis could be made. Yet, most studies find positive correlation between high HGF levels and regeneration. Prospective studies investigating HGF and other growth factors, hyaluronic acid and interleukins 1 and 6 in correlation with liver regeneration measured sequentially through e.g. volumetry, and liver function parameters, preferably expanding the analysis to include dynamic liver function tests, are needed to sufficiently illustrate the connection between biomolecule levels and clinical outcomes.

Use of serum hyaluronic acid as a biomarker of endothelial glycocalyx degradation in dogs with septic peritonitis.

To describe daily changes in serum concentrations of hyaluronic acid (HA), a biomarker of endothelial glycocalyx degradation, in dogs with septic peritonitis and to determine whether relationships exist among serum concentrations of HA and biomarkers of inflammation and patient fluid status. 8 client-owned dogs. Serum samples that had been collected for a previous study and stored at -80°C were used. Blood samples were collected at admission and daily thereafter during hospitalization and were analyzed for concentrations of HA and interleukins 6, 8, and 10. Patient data including acute patient physiologic and laboratory evaluation score, type and amount of fluids administered daily, and daily CBC and lactate concentration results were recorded. To determine the significant predictors of HA concentration, a general linear mixed model for repeated measures was developed. All dogs survived to discharge. Concentrations of HA ranged from 18 to 1,050 ng/mL (interquartile [25th to 75th percentile] range, 49 to 119 ng/mL) throughout hospitalization. Interleukin-6 concentration was a significant predictor of HA concentration as was total administered daily fluid volume when accounting for interleukin-6 concentration. When fluid volume was analyzed independent of inflammatory status, fluid volume was not a significant predictor. Concentrations of HA did not significantly change over time but tended to increase on day 2 or 3 of hospitalization. Results supported the theory that inflammation is associated with endothelial glycocalyx degradation. Dogs recovering from septic peritonitis may become more susceptible to further endothelial glycocalyx damage as increasing fluid volumes are administered.