Serum Hyaluronic Acid Research Articles

Sex-specific effects of calving season on joint health and biomarkers in Montana ranchers

BackgroundAgricultural workers have a higher incidence of osteoarthritis (OA), but the etiology behind this phenomenon is unclear. Calving season, which occurs in mid- to late-winter for ranchers, includes physical conditions that may elevate OA risk. Our primary aim was to determine whether OA biomarkers are elevated at the peak of calving season compared to pre-season, and to compare these data with joint health survey information from the subjects. Our secondary aim was to detect biomarker differences between male and female ranchers.MethodsDuring collection periods before and during calving season, male (n = 28) and female (n = 10) ranchers completed joint health surveys and provided samples of blood, urine, and saliva for biomarker analysis. Statistical analyses examined associations between mean biomarker levels and survey predictors. Ensemble cluster analysis identified groups having unique biomarker profiles.ResultsThe number of calvings performed by each rancher positively correlated with plasma IL-6, serum hyaluronic acid (HA) and urinary CTX-I. Thiobarbituric acid reactive substances (TBARS), a marker of oxidative stress, was significantly higher during calving season than pre-season and was also correlated with ranchers having more months per year of joint pain. We found evidence of sexual dimorphism in the biomarkers among the ranchers, with leptin being elevated and matrix metalloproteinase-3 diminished in female ranchers. The opposite was detected in males. WOMAC score was positively associated with multiple biomarkers: IL-6, IL-2, HA, leptin, C2C, asymmetric dimethylarginine, and CTX-I. These biomarkers represent enzymatic degradation, inflammation, products of joint destruction, and OA severity.ConclusionsThe positive association between number of calvings performed by each rancher (workload) and both inflammatory and joint tissue catabolism biomarkers establishes that calving season is a risk factor for OA in Montana ranchers. Consistent with the literature, we found important sex differences in OA biomarkers, with female ranchers showing elevated leptin, whereas males showed elevated MMP-3.

Rise in serum hyaluronic acid, marker of liver sinusoidal endothelial injury, correlates with adverse outcome in patients with rodenticidal hepatotoxicity

Rise in serum hyaluronic acid, marker of liver sinusoidal endothelial injury, correlates with adverse outcome in patients with rodenticidal hepatotoxicity

Case report: Granuloma after infection of commercial hyaluronic acid serum

Case report: Granuloma after infection of commercial hyaluronic acid serum

Hyaluronic acid as a predictor of exacerbation of occupational chronic obstructive pulmonary disease

The frequency of exacerbations of chronic obstructive pulmonary disease (COPD) is one of the main factors determining the outcome. The search for biomarkers which reflect the risk of exacerbations is one of the urgent scientific and practical objectives. Aim. The study aimed to analyze the relationship between the serum concentration of hyaluronic acid (HA) and the frequency of exacerbations of occupational COPD caused by exposure to silica dust and to substantiate the use of HA as a predictor of exacerbations of COPD. Methods. 78 individuals with a diagnosis of occupational COPD were examined. Respiratory function was assessed based on forced vital capacity of the lungs (FVC, %), the forced expiratory volume in 1 second (FEV1, %) and the calculated ratio of these parameters (FEV1/FVC, %), i.e., modified Tiffno index. The serum concentration of hyaluronic acid (ng/ml) was determined in all individuals using solid-phase enzyme-linked immunosorbent assay (ELISA). The absolute blood level of eosinophils (cell/μl) was determined by a unified method of morphological study of hemocytes with white blood cell differential count. Results. Serum HA concentration in patients with occupational COPD with frequent exacerbations was 25% higher than in the patients with rare exacerbations (the difference was statistically significant; р = 0,004). The analysis of the obtained data showed that the most significant moderate correlation was found between the level of HA and the frequency of COPD exacerbations (direct relationship, r = 0.32; p < 0.05), and FEV1 and the frequency of COPD exacerbations (feedback, r = -0.32;p < 0.05). A weak relationship was found between the relative number of eosinophils and the frequency of COPD exacerbations (direct relationship, r = 0.2; p < 0.05). Weak correlations were also found between the level of HA and FEV1 (feedback, r = -0.23; p < 0.05), between the level of HA and the relative number of eosinophils (direct relationship, r = 0.18; p < 0.05). Conclusion. Quantitative analysis of serum HA in patients with occupational COPD can be used in clinical practice as a biochemical marker for assessing the risk of exacerbations and progression of bronchopulmonary pathology.

Accuracy of noninvasive methods for the diagnosis of liver fibrosis in children with chronic viral hepatitis.

Liver biopsy is the reference standard for assessing liver fibrosis. Moreover, it is an invasive procedure. Transient elastography (TE) is an accurate, noninvasive method for evaluating liver stiffness as a surrogate of liver fibrosis. The aspartate aminotransferase to platelet ratio index (APRI) and Hyaluronic acid (HA) are noninvasive alternatives to liver biopsy for detecting hepatic fibrosis. This study aimed to identify the accuracy of APRI, HA, and TE concerning liver biopsy in children with chronic viral hepatitis. This cross-sectional study included 50 children, 5-18years with chronic viral hepatitis B (HBV) or hepatitis C (HCV) who underwent liver biopsy within nine months of laboratory tests, determining APRI & performing TE. Twenty healthy children of age and sex-matching patients were included as a control group for the serum HA levels. The histopathological findings of the studied cases showed seven cases with (F0) fibrosis, 36 cases with mild (F1,2), two children with moderate (F3,4), and five children with severe (F5,6). The median (IQR) of steatosis was 4 (three had HCV). When correlating TE, APRI, and HA values in all cases with their laboratory data, there was a positive correlation between ALT and APRI values (P-value = 0.000), a positive correlation between AST and HA values (P-value = 0.02), and a negative correlation between stiffness and APRI. The sensitivity of HA, APRI, and TE compared to fibrosis detected by histopathology was 60.5, 65.1, and 60.5%, and their specificity was 71.4, 57.1, and 85.7%, respectively. TE was significantly higher in a group with (moderate to severe) fibrosis. APRI, HA, and TE are good indicators of the presence of fibrosis almost with the same accuracy. TE is the only method to differentiate mild cases from those with significant fibrosis.

Effect of Celecoxib Administration on the Skin of 40-Week-Old Mice.

Various side effects associated with the use of nonsteroidal anti-inflammatory drugs (NSAIDs) in analgesia have been reported. Among the NSAIDs, celecoxib has fewer side effects and is often used in therapeutic applications. However, the effect of celecoxib on aged skin is unknown. In this study, we investigated the effects of celecoxib administration on the skin of aged mice. We analyzed a 40-week-old mouse model and a 10-week-old mouse as the control group. The animals were orally administered celecoxib for four consecutive days and then killed and dissected the day after the last dose. In aged mice treated with celecoxib, the water content of the stratum corneum, which is one of the markers of dry skin, was lower than that in the control and young mice groups. In addition, serum hyaluronic acid, creatinine, and inflammatory cytokines in the collected blood samples of aged mice were elevated compared to those in other mice groups, suggesting the onset of acute renal injury. Therefore, it was considered that acute renal injury occurred from the administration of celecoxib to aged mice, whereas dry skin developed by the promotion of inflammatory cytokine secretion and release into the bloodstream in this group.

Circulating tissue inhibitor of metalloproteinases 1 (TIMP-1) at COVID-19 onset predicts severity status.

Systemic biomarkers for severity of SARS-CoV-2 infection are of great interest. In this study, we evaluated a set of collagen metabolites and extracellular matrix remodeling biomarkers including procollagen type III amino terminal propeptide (PIIINP), tissue inhibitor of metalloproteinases 1 (TIMP-1) and hyaluronic acid (HA) as prognostic indicators in COVID-19 patients. Ninety COVID-19 patients with the absence of chronic liver diseases were enrolled. Serum PIIINP, TIMP-1, and HA were measured and correlated with inflammatory indices and clinical variables. Patients were stratified for disease severity according to WHO criteria in two groups, based on the requirement of oxygen support. Serum TIMP-1, but not PIIINP and HA was significantly higher in patients with WHO score ≥5 compared to patients with WHO score <5 [PIIINP: 7.2 (5.4-9.5) vs. 7.1 (4.5-9.9), p = 0.782; TIMP-1: 298.1 (20.5-460) vs. 222.2 (28.5-452.8), p = 0.01; HA: 117.1 (55.4-193.7) vs. 75.1 (36.9-141.8), p = 0.258]. TIMP-1 showed moderate correlation with CRP (r = 0.312, p = 0.003) and with LDH (r = 0.263, p = 0.009). CRP and serum LDH levels were significantly higher in COVID-19 patients with WHO score ≥5 compared to the group of patients with WHO score < 5 [15.8 (9-44.5) vs. 9.3 (3.4-33.8), p = 0.039 and 373 (282-465) vs. 289 (218-383), p = 0.013, respectively]. In patients with COVID-19, circulating TIMP-1 was associated with disease severity and with systemic inflammatory index, suggesting that TIMP-1 could represent a promising non-invasive prognostic biomarker in COVID-19 patients. Interestingly, our results prompted that serum TIMP-1 level may potentially be used to select the patients for therapeutic approaches targeting matrix metalloproteases pathway.

The Association Between Serum Hyaluronic Acid Levels and Routine Liver Function Tests in Liver Fibrotic HCV Patients

Abstract Introduction/Objective Liver fibrosis is the excessive accumulation of extracellular matrix proteins, including collagen, that occurs in most types of chronic liver diseases. Advanced liver fibrosis results in cirrhosis, liver failure, and portal hypertension and often requires liver transplantation. Markers (NIM) of Liver Fibrosis, such as hyaluronic acid, help evaluate the stage of fibrosis in patients with liver fibrosis. This study aims to investigate whether or not there is a correlation between serum hyaluronic acid levels and liver function tests in patients who suffer from chronic HCV-induced liver fibrosis. Methods/Case Report This study was conducted on 118 (60 males and 58 females) patients recruited from Internal Medicine Dept., Mansoura University Hospitals, Egypt. The patients were diagnosed with chronic HCV-induced liver fibrosis. Also, we included 50 healthy comparable control subjects (27 males and 23 females). Routine laboratory tests such as AST, ALT, albumin, total bilirubin, and platelets count were performed. The APRI was calculated as [AST/ (upper limits of normal)/ platelets count 109/L]×100. The AST-ALT ratio was calculated as [AST/ ALT]. According to the manufacturer's instructions, the serum levels of hyaluronic acid were measured by radioimmunoassay. Results (if a Case Study enter NA) We observed a statistically significant positive correlation was found between serum hyaluronic acid levels and APRI (r=0.3, p=0.001), ALT (r=0.3, p=0.003), AST (r=0.3 and p=0.01), and total bilirubin (r=0.3 and p=0.002). Furthermore, there was a statistically significant negative correlation between serum hyaluronic acid levels and albumin (r= -0.43, p=0.0001), and platelets count (r= -0.4, p=0.0001). Conclusion The levels of hyaluronic acid in the body and the results of other liver function tests tend to rise in tandem, which suggests a significant relationship between the two. This may assist us in constructing an accurate picture of the patient's condition, which will lead to a more precise diagnosis.

ALL-548 Assessment of Serum Hyaluronic Acid and Ferritin Levels in Children With Acute Lymphoblastic Leukemia

Serum levels of hyaluronic acid (HA) and ferritin are high in newly diagnosed children with acute lymphoblastic leukemia. To evaluate the level of serum hyaluronic acid and ferritin in patients with ALL at diagnosis and in remission and investigate their impact on disease development and prognosis. A prospective cross-sectional study was conducted in the Central Teaching Hospital of Pediatrics, Baghdad, Iraq from January to October 2020. The study was conducted on hospitalized patients. For each patient, consent was obtained to take peripheral blood (PB) and/or bone marrow (BM) samples, and serum samples were analyzed in a private laboratory. 60 subjects were enrolled in this study, 40 ALL patients as cases (20 patients at diagnosis before starting chemotherapy and 20 patients in remission but still under therapy); and 20 age and sex-matched healthy subjects as controls. Both Band T-ALL subtypes were included. The age was less than 15 years. The patients were randomly collected in relation to gender. Patients on iron supplementation, with liver diseases, and those with other types of malignancy were excluded. The diagnosis of ALL was based on morphological assessments of the stained PB and BM smears according to the standard French-American-British criteria and confirmed by cytochemical stains and flow cytometric immunophenotyping. Patients with complete remission were also evaluated by morphological examination. Serum HA was measured using a commercially available sandwich ELISA kit while serum ferritin was measured by an immunoassay analyzer. Serum HA in newly diagnosed patients with ALL was significantly higher than either patients in remission (P-value 0.022) or controls (P-value 0.001). Both newly diagnosed patients and those in remission had elevated levels of serum ferritin with no significant difference. Serum levels of HA correlated positively with both serum ferritin and LDH (p<0.001). Our data suggest that serum level of hyaluronic acid could have a role in the malignant process of ALL and may serve as a possible marker for aggressiveness. Further studies on larger populations and on patients with relapse and follow-up of patients for a longer period of time are recommended.

CD44-targeted nanoparticles with GSH-responsive activity as powerful therapeutic agents against breast cancer

DOX-loaded nanoparticles able to actively target CD44-receptors and respond to redox stimuli were proposed as non-conventional chemotherapeutic strategy in breast cancer. A covalent conjugate of human serum albumin and hyaluronic acid was prepared and assembled by a GSH-mediated desolvation in disulfide-crosslinked solid nanoparticles with mean diameter of 120 nm ± 3.4. The effective internalization of nanoparticles in cancer cells via CD44-receptors, together with the more efficient intracellular release, resulted in a significant increase of drug efficacy, with IC50 reduced from 0.9959 and 2.516 μg mL−1 to 0.4014 and 0.3094 μg mL−1 for MCF-7 and MDA-MB-231, respectively. Conversely, no enhancement in drug toxicity was recorded in healthy MCF-10A cells. The efficacy of the proposed formulation was further investigated in the different biological steps involved in metastasis process, paving the way for further in vivo experiments.

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Journal of Cosmetic DermatologyVolume 21, Issue 9 p. i-i FEATURED COVERFree Access Featured Cover First published: 26 September 2022 https://doi.org/10.1111/jocd.15344AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Abstract The cover image is based on the Original Article Multicenter evaluation of a topical hyaluronic acid serum by Deanne Mraz Robinson et al., https://doi.org/10.1111/jocd.15241. Volume21, Issue9September 2022Pages i-i RelatedInformation

Compound Biejia-Ruangan tablet as an adjunctive therapy to entecavir for chronic hepatitis B complicated with hepatic fibrosis: A systematic review and meta-analysis of randomized controlled trials.

Background:The compound Biejia-Ruangan tablet (CBRT), as an adjunctive therapy to entecavir, is a potential treatment for hepatic fibrosis (HF) in patients with chronic hepatitis B (HBV). However, the present study yielded inconsistent results. In this systematic review and meta-analysis, we comprehensively investigated the efficacy and safety of CBRT as an adjunctive modality to entecavir for the treatment of HBV infection complicated with HF.Methods:We searched the Cochrane Library, PubMed, Embase, CNKI, VIP, CBM, and Wangfang databases through April 1, 2022, for randomized controlled trials (RCTs) assessing the effect and safety of CBRT as an adjunctive modality to entecavir for HBV complicated with HF. The primary outcomes were biochemical parameters of serum hyaluronic acid, laminin (LN), pretype-III collagen (PC-III), and type IV collagen (IV-C). The secondary outcomes were liver function indices of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBiL) levels, total effect rate, and occurrence rate of adverse events. Two researchers independently conducted study selection, data extraction, and quality assessment. Statistical analysis was performed using the RevMan 5.3 software.Results:Eight RCTs involving 747 patients were included. Compared with entecavir monotherapy, CBRT as an adjunctive therapy to entecavir exerted more encouraging effect in serum levels of hyaluronic acid (mean difference [MD] = –28.15; 95% confidence interval [CI]: –43.82 to –12.47; P < .001), LN (MD = –29.46; 95% CI: –50.69 to –8.23; P < .001), PC-III (MD = –11.83; 95% CI: –19.43 to –4.23; P < .001), and IV-C (MD = –19.62; 95% CI: –29.76 to –9.49; P < .001); levels of serum ALT (MD = –16.83; 95% CI: –26.30 to –7.36; P < .001), AST (MD = –20.52; 95% CI: –33.11 to –7.93; P < .001), and TBiL (MD = –7.54; 95% CI: –11.58 to –3.49; P < .001); and total effect rate (odds ratio = 3.53; 95% CI: 1.71–7.29; P < .001). Meta-analysis results also showed that CBRT as an adjunctive therapy to entecavir had a lower occurrence rate of adverse events (odds ratio = 0.54; 95% CI: 0.22–1.34; P < .001) than entecavir alone.Conclusion:The results of this study showed that CBRT as an adjunctive modality to entecavir may benefit HBV patients complicated with HF. High-quality RCTs are needed to confirm the current findings in the future.

Phloridzin Reveals New Treatment Strategies for Liver Fibrosis.

Liver fibrosis is an urgent public health problem which is difficult to resolve. However, various drugs for the treatment of liver fibrosis in clinical practice have their own problems during use. In this study, we used phloridzin to treat hepatic fibrosis in the CCl4-induced C57/BL6N mouse model, which was extracted from lychee core, a traditional Chinese medicine. The therapeutic effect was evaluated by biochemical index detections and ultrasound detection. Furthermore, in order to determine the mechanism of phloridzin in the treatment of liver fibrosis, we performed high-throughput sequencing of mRNA and lncRNA in different groups of liver tissues. The results showed that compared with the model group, the phloridzin-treated groups revealed a significant decrease in collagen deposition and decreased levels of serum alanine aminotransferase, aspartate aminotransferase, laminin, and hyaluronic acid. GO and KEGG pathway enrichment analysis of the differential mRNAs was performed and revealed that phloridzin mainly affects cell ferroptosis. Gene co-expression analysis showed that the target genes of lncRNA were obvious in cell components such as focal adhesions, intercellular adhesion, and cell–substrate junctions and in metabolic pathways such as carbon metabolism. These results showed that phloridizin can effectively treat liver fibrosis, and the mechanism may involve ferroptosis, carbon metabolism, and related changes in biomechanics.

Methods of a New Chronic Pancreatitis and Spontaneous Pancreatic Cancer Mouse Model Using Retrograde Pancreatic Duct Injection of Dibutyltin Dichloride.

The current study aimed to develop a new chronic pancreatitis and spontaneous pancreatic cancer model on C57/BL6 mouse through retrograde pancreatic duct injection of dibutyltin dichloride (DBTC) and explore its basic pathological changes as compared to the previous published chronic pancreatitis model through tail vein injection of DBTC with alcohol drinking. C57/BL6 mice were randomly divided into 3 groups: CG (control group; n = 15), VG (tail vein injection of DBTC (8 mg/kg) with 10% alcohol drinking group; n = 20), and PG (retrograde pancreatic duct injection of DBTC group (1 mg/kg); n = 30). Five mice in each group were sacrificed at a specific time point after the first treatment. The pathological section was observed. The activities of amylase, bilirubin, and hyaluronic acid in serum were determined. The expression of fibronectin, COL1A1, α-SMA, MMP-1, and TIMP-1 in the pancreas was assayed. Severe fibrosis of the pancreas with inflammatory cell infiltration could be observed on day 21 in the PG. In the VG, slight fibrosis of the pancreas with inflammatory cell infiltration was observed on day 28. There were significant differences in serum amylase, bilirubin, and hyaluronic acid levels between the PG and VG. The protein level of COL1A1 and α-SMA significantly increased in the PG. The mRNA expression of TIMP-1 is upregulated and the MMP-1 mRNA level is downregulated in the PG. Finally, typical neoplastic pathological change is significantly obvious in the PG. In conclusion, we established and validated a new chronic pancreatitis (CP) and spontaneous pancreatic cancer mouse model through retrograde injection of DBTC into the pancreatic duct. Previously reported mouse model through tail vein injection of DBTC with alcohol drinking could not cause obvious CP and neoplastic pathological change in mice.

Extracts of Periplaneta americana alleviate hepatic fibrosis by affecting hepatic TGF-β and NF-κB expression in rats with pig serum-induced liver fibrosis.

Liver fibrosis is caused by continuous wound healing responses to various harmful stimuli, including viral infection, drugs, alcohol, and autoimmune liver disease. The purpose of this study was to examine the effects of extracts of Periplaneta americana (EPA) in rats with pig serum-induced liver fibrosis to preliminarily assess the antifibrotic effect of EPA. Seventy rats were randomly divided into 7 groups (10 rats in each group): HC, the healthy control group; FC, the fibrotic control group; TL, low-dose EPA treatment group group; TM, medium-dose EPA group; TH, high-dose EPA treatment group; TC1, Panax notoginseng/Salvia mitiorrhiza treatment control group 1; TC2, colchicine treatment control group 2. TC1 and TC2 were used as the positive control to demonstrate the difference between EPA and the effects of other compounds. The liver fibrosis model was induced by intraperitoneal injection of 0.5 mL pig serum twice a week for 13 weeks in all groups except for the HC group. The hepatic fibrosis model was established at the 7th week, and followingly, the corresponding compounds were administered once a day in all groups for 6 weeks. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity was determined in rat blood serum. We also measured liver fibrosis-related serum markers, including hyaluronic acid (HA), mucin layer (LN), type III pre-collagen (PC-III) and type IV collagen (IV-C). Hematoxylin and eosin (H&E) and Masson stainings were used to assess liver morphology and determine the stage of fibrosis. Immunohistochemistry was used to detect the protein expression of NF-κB, α-smooth muscle actin (α-SMA), transforming growth factor-β1 (TGF-β1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in rat liver tissue. Compared with that of the HC group, the liver tissue of the FC group presented obvious liver damage and collagen deposition. The serum levels of ALT, AST, HA, LN, PC-III and IV-C and the expression of NF-κB, α-SMA, TGF-β1 and TIMP-1 in the FC group were significantly higher than those in the HC group, the EPA treatment groups, the TC1 group and the TC2 group (P < 0.01). The levels of serum ALT, AST, HA, LN, PC-III and IV-C and the expression of α-SMA, NF-κB, TGF-β1 and TIMP-1 in the TL, TC1 and TC2 groups were significantly higher than those TM and TH groups (P < 0.05). EPA treatment significantly improved liver function, decreased collagen deposition and reversed the pathological changes related to liver fibrosis. We found that EPA could reduce liver inflammation, suppress liver cell degeneration and necrosis, and reduce the formation of liver fibrous tissue. Its mechanism might be associated with inhibiting the expression of TGF-β1, TIMP-1, NF-κB and α-SMA to block signal transduction pathways in the hepatic fibrosis process. Therefore, EPA, as a traditional Chinese medicine, might be potentially used to prevent and treat hepatic fibrosis in the future. However, further more experiments are necessary to verify its effectiveness and possible signaling pathways.

Evaluation of different blood tests in dogs with extrahepatic portosystemic shunts to assess shunt closure after surgical treatment.

To determine the sensitivity and specificity of different individual and combined blood tests to assess extrahepatic portosystemic shunt (EHPSS) closure after gradual attenuation of EHPSS in dogs. Clinical prospective study. Twenty client-owned dogs with EHPSS. Fasting ammonia (FA), preprandial, postprandial, and paired serum bile acids (SBA), the lidocaine/monoethylglycylxylidide (L/MEGX) test, and serum hyaluronic acid (SHA) were performed at diagnosis, and 1, 3, and 6 months postoperatively. Transsplenic portal scintigraphy was performed to determine EHPSS closure 3 months postoperatively. Their sensitivity and specificity in determining shunt closure postoperatively were calculated. When assessing a single blood parameter, FA had the highest specificity (100%), whereas SHA and MEGX measured 15 min after lidocaine administration (T15) had the highest sensitivity (96.9% and 96.2%, respectively) for determining shunt closure postoperatively. The most promising blood test combinations were SHA (sensitivity 96.9%, specificity 81.8%), combined with the L/MEGX test (MEGX at T15: sensitivity 100%, specificity 72.4%) or the L/MEGX test (MEGX at T15) combined with either FA (sensitivity 100%, specificity 82.8%) or postprandial SBA (sensitivity 100%, specificity 81.5%). Both SHA and the L/MEGX test were sensitive tests for determining shunt closure after gradual attenuation of EHPSS. Test performances could even be improved by combining these tests with each other or with traditional tests such as FA or postprandial SBA. Although SHA and the L/MEGX test are sensitive blood tests for determining EHPSS closure, especially when combined with traditional blood tests, imaging is still needed to confirm EHPSS closure.

Clinical Significance of Serum Collagen Type IV and Procollagen Type III N-Peptide Levels in Diagnosis and Differential Diagnosis of Lymphedema.

Background: Lymphatic endothelial cells production or modification were closely related to the extracellular matrix (ECM) molecules. The serum hyaluronic acid (HA), laminin (LN), procollagen type III N-peptide (PIIINP), and collagen type IV (CGIV) levels were researched to explore the clinical significance of serum ECM proteins in the diagnosis and differentiation of lymphedema. Methods: Fifty-five patients were enrolled. They were divided into primary lymphedema (PLE), secondary lymphedema (SLE), and venous edema (VE) groups. Twenty-two healthy controls were also recruited as normal control (NC). Serum HA, LN, PIIINP, and CGIV levels of all subjects were assessed using chemiluminescence immunoassay. Statistical analysis and receiver operating characteristic (ROC) curves were used to data analysis. Results: The serum levels of CGIV were significantly decreased in both PLE and SLE groups compared with those in the NC group. Reduced serum CGIV levels were associated with the severity of lymphedema. The serum levels of CGIV and PIIINP were identified decreased in both PLE and SLE groups compared with those in the VE group. However, the levels of serum HA and LN were not observed significantly changed in both PLE and SLE groups than those in NC or VE group. Furthermore, ROC curve indicated that serum CGIV and PIIINP were capable of providing good diagnostic and differential diagnostic efficacy at the most appropriate cutoff point value. Conclusion: The serum levels of CGIV may have clinical significance in the diagnosis of lymphedema. CGIV and PIIINP may play a role in the differentiation of lymphedema from VE.

Clinical and laboratory findings following transplantation of allogeneic adipose-derived mesenchymal stromal cells in knee osteoarthritis, a brief report

ABSTRACT Background Mesenchymal stromal cells (MSCs) injection has been proposed as an innovative treatment for knee osteoarthritis (KOA). Since, allogeneic MSCs can be available as off-the-shelf products, they are preferable in regenerative medicine. Among different sources for MSCs, adipose-derived MSCs (AD-MSCs) appear to be more available. Methods Three patients with KOA were enrolled in this study. A total number of 100 × 106 AD-MSCs was injected intra-articularly, per affected knee. They were followed up for 6 months by the assessment of clinical outcomes, magnetic resonance imaging (MRI), and serum inflammatory biomarkers. Results The primary outcome of this study was safety and feasibility of allogeneic AD-MSCs injection during the 6 months follow-up. Fortunately, no serious adverse events (SAEs) were reported. Assessment of secondary outcomes of visual analogue scale (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and knee osteoarthritis outcome score (KOOS) indicated improvement in all patients. Comparison between baseline and endpoint findings of MRI demonstrated a slight improvement in two patients. In addition, decrease in serum cartilage oligomeric matrix protein (COMP) and hyaluronic acid (HA) indicated the possibility of reduced cartilage degeneration. Moreover, quantification of serum interleukin-10 (IL-10) and interleukin-6 (IL-6) levels indicated that the host immune system immunomodulated after infusion of AD-MSCs. Conclusion Intra-articular injection of AD-MSCs is safe and could be effective in cartilage regeneration in KOA. Preliminary assessment after six-month follow-up suggests the potential efficacy of this intervention which would need to be confirmed in randomized controlled trials on a larger population. Trial registration This study was registered in the Iranian registry of clinical trials (https://en.irct.ir/trial/46) in 24 April 2018 with identifier IRCT20080728001031N23.

Longitudinal association of infrapatellar fat pad signal intensity alteration with biochemical biomarkers in knee osteoarthritis.

To explore the longitudinal association of quantitative infrapatellar fat pad (IPFP) signal intensity alteration with OA-related biomarkers. Eighteen OA-related biochemical biomarkers of 600 knee OA participants in the Foundation for the National Institutes of Health OA Biomarkers Consortium (FNIH) study were extracted. The quantitative IPFP signal intensity measures were acquired based on magnetic resonance imaging, including mean value [Mean (IPFP)] and standard deviation [sDev (IPFP)] of the whole IPFP signal intensity, median value [Median (H)] and upper quartile value [UQ (H)] of high signal intensity, the ratio of volume of high signal intensity to volume of whole IPFP signal intensity [Percentage (H)] and Clustering factor (H). The linear mixed-effect model was applied to determine the longitudinal associations between IPFP signal intensity alteration and biochemical biomarkers over 2 years. All IPFP measures except for Clustering factor (H) were positively associated with urine collagenase-cleaved type II collagen neoepitope (uC2C), urine C-terminal cross-linked telopeptide of type II collagen (uCTX-II), urine C-terminal cross-linked telopeptide of type I collagen-α (uCTX-Iα) and urine N-terminal cross-linked telopeptide of type I collagen (uNTX-I). Mean (IPFP), Median (H) and Percentage (H) were positively associated with the nitrated form of an epitope located in the triple helix of type II collagen (Coll2-1 NO2). Mean (IPFP), Median (H) and UQ (H) were positively associated with sCTX-I and uCTX-Iβ. Positive associations between sDev (IPFP), Percentage (H) and serum hyaluronic acid (sHA) were found. Our results suggest a role of IPFP signal intensity alteration in joint tissue remodelling on a molecular level.

Prognostic significance of preoperative hyaluronic acid level in patients with hepatocellular carcinoma.

Serum hyaluronic acid (HA) levels are increased in patients with solid tumors, and may predict outcomes. However, as HA levels also correlate with the degree of liver fibrosis, the prognostic significance of serum HA levels in patients with hepatocellular carcinoma (HCC) is unclear. A total of 656 consecutive patients who underwent hepatic resection for HCC were divided into two groups by serum HA level (high HA [≥200ng/mL], n=248; low HA [<200ng/mL], n=408). Clinicopathological characteristics and postoperative survival were compared between groups. Moreover, 1:1 propensity score matching analysis was applied to adjust characteristics between groups. Both the 5-year overall and relapse-free survival rates (OSR and RFSR) in the low HA group were significantly better than those in the high HA group (59.8% vs. 38.6%, respectively, p<0.001 and 24.5% vs. 13.1%, respectively, p<0.001). After propensity score matching, two comparable groups of 124 patients each were obtained. However, both the 5-year OSR and RFSR in the low HA group remained significantly better than those in the high HA group (57.4% vs. 38.3%, respectively, p=0.006 and 22.5% vs. 14.7%, respectively, p=0.003). High preoperative HA level predicts poor postoperative survival of patients with HCC. undergoing hepatic resection.