The Value of the Measurement of Urinary Hyaluronic Acid Levels for the Diagnosis of Bladder Cancer

Objective To investigate the value of the measurement of urinary hyaluronic acid (HA) levels for the diagnosis of bladder cancer and the possibility of replacing ELISA-like assay with radioimmunoassay to detect the levels of urinary HA. Methods Using the ELISA-like assay and radioimmunoassay at the same time to measure the HA levels in the urine specimens from 49 bladder cancer patients, 12 benign bladder tumor patients, 30 other genitourinary disease patients and 20 normal controls. Results There is not much difference between the consequences of the urinary HA levels whether we used the ELISA-like assay or radioimmunoassay to detect every specimen (P>0.05). When we used the results with radioimmunoassay for analysis, we found the levels of urinary HA of bladder cancer patients were 2–4 times than those of the benign bladder tumor patients, other genitourinary disease patients or normal individuals (P<0.01); With 137.5 ngHA/mg protein (113.6±23.9 ng/mg) as a minimum cutoff limit, this assay had a good sensitivity (91.8%) and specificity (91.9%) for the diagnosis of bladder cancer. Its difference in sensitivity meant a lot when compared with urine cytology (48.9%,P<0.01). Conclusion The urinary HA assay is a simple, convenient, noninvasive credible and cheap method with satisfactory sensitivity and specificity for the diagnosis of bladder carcinoma; radioimmunoassay is also a good means to measure the urinary HA levels. Key words Bladder carcinoma - Hyaluronic acid - Urine

Different concentrations of hyaluronic acid eye drops for dry eye syndrome: a systematic review and Meta-analysis

AIM:To compare high or low concentration of hyaluronic acid eye drops(HY)for dry eye syndromes(DES).METHODS:Randomized controlled trials(RCTs)comparing various concentrations of HY were searched in PubMed,Embase,Web of Science,Cochrane,SinoMed,CNKI,Wanfang Database,CQVIP,and Chinese journals databases between inception and July 2023.Pooled standardized mean differences(SMD)or weighted mean difference(WMD)with 95%confidence intervals(CI)from RCTs evaluating Schirmer’s I test(SIT),corneal fluorescein staining score(CFS),tear breakup time(TBUT),DES score(DESS),and Ocular Surface Disease Index(OSDI)were calculated.Sensitivity analysis,Egger’s test and Meta-regression analysis were performed for all indicators.RESULTS:We conducted a Meta-analysis of 10 RCTs that met the inclusion criteria,involving 1796 cases.High-concentrations group significantly improved the outcome of CFS according to random effects modelling(SMD,-3.37;95%CI,-5.25 to-1.48;P=0.0005).The rest of the results were not statistically significant,including indicators such as SIT,TBUT,DESS and OSDI.CONCLUSION:For dry eyes with positive corneal staining,a high concentration of HY is recommended,whereas in other cases,a high concentration of HY does not offer a more pronounced advantage over a low concentration of HY in the treatment of dry eyes.

Impacts of mesenchymal stem cells and hyaluronic acid on inflammatory indicators and antioxidant defense in experimental ankle osteoarthritis

BACKGROUND No effective treatment guarantees full recovery from osteoarthritis(OA),and few therapies have disadvantages.AIM To determine if bone marrow mesenchymal stem cells(BMMSCs)and hyaluronic acid(HA)treat ankle OA in Wistar rats.METHODS BMMSCs were characterized using flow cytometry with detection of surface markers[cluster of differentiation 90(CD90),CD105,CD34,and CD45].Fifty male Wistar rats were divided into five groups of 10 rats each:Group I,saline into the right tibiotarsal joint for 2 days;Group II,monosodium iodate(MIA)into the same joint;Groups III,MIA+BMMSCs;Group IV,MIA+HA;and Group V,MIA+BMMSCs+HA.BMMSCs(1×106 cells/rat),HA(75μg/rat),and BMMSCs(1×106 cells/rat)alongside HA(75μg/rat)were injected intra-articularly into the tibiotarsal joint of the right hind leg at the end of weeks 2,3,and 4 after the MIA injection.RESULTS The elevated right hind leg circumference values in the paw and arthritis clinical score of osteoarthritic rats were significantly ameliorated at weeks 4,5,and 6.Lipid peroxide significantly increased in the serum of osteoarthritic rats,whereas reduced serum glutathione and glutathione transferase levels were decreased.BMMSCs and HA significantly improved OA.The significantly elevated ankle matrix metalloproteinase 13(MMP-13)mRNA and transforming growth factor beta 1(TGF-β1)protein expression,and tumor necrosis factor alpha(TNF-α)and interleukin-17(IL-17)serum levels in osteoarthritic rats were significantly downregulated by BMMSCs and HA.The effects of BMMSCs and HA on serum TNF-αand IL-17 were more potent than their combination.The lowered serum IL-4 levels in osteoarthritic rats were significantly upregulated by BMMSCs and HA.Additionally,BMMSCs and HA caused a steady decrease in joint injury and cartilage degradation.CONCLUSION BMMSCs and/or HA have anti-arthritic effects mediated by antioxidant and anti-inflammatory effects on MIAinduced OA.MMP-13 and TGF-β1 expression improves BMMSCs and/or HA effects on OA in Wistar rats.

Intra-articular interventions in osteoarthritis:Navigating the landscape of hyaluronic acid,mesenchymal stem cells,and plateletrich plasma

Osteoarthritis(OA)poses a substantial burden on patients,leading to pain,functional decline,and reduced quality of life.While conventional treatments focus on symptom management,disease-modifying interventions are yet to be established.This review explores the efficacy of intra-articular interventions,particularly hyaluronic acid(HA),mesenchymal stem cells(MSCs),and platelet-rich plasma(PRP),in the context of OA management.HA injections,with diverse formulations like Hylan G-F20,sodium hyaluronate,and hyaluronan,present varying outcomes,necessitating a nuanced understanding of their effectiveness and timing.MSC therapy,derived from adipose tissue,umbilical cord,or bone marrow,shows promising results in clinical improvement,with adipose-derived MSCs demonstrating efficacy in maintaining benefits over 6 mo.Conversely,bone-marrow-derived MSCs show limited effectiveness,highlighting the need for sourcespecific considerations.PRP has emerged as a superior option for long-term pain reduction and quality of life improvement,with leukocyte-poor formulations and a critical platelet count of 10 billion demonstrating optimal results.This comprehensive analysis underscores the potential of intra-articular interventions in OA management,emphasizing the need for personalized and evidence-based approaches to enhance treatment efficacy and patient outcomes.

3D bioprinted hyaluronic acid‑based cell‑laden scaffold for brain microenvironment simulation

Treatments for lesions in central nervous system(CNS)are always faced with challenges due to the anatomical and physiological particularity of the CNS despite the fact that several achievements have been made in early diagnosis and precision medicine to improve the survival and quality of life of patients with brain tumors in recent years.Understanding the complexity as well as role of the microenvironment of brain tumors may suggest a better revealing of the molecular mechanism of brain tumors and new therapeutic directions,which requires an accurate recapitulation of the complex microenvironment of human brain in vitro.Here,a 3D bioprinted in vitro brain matrix-mimetic microenvironment model with hyaluronic acid(HA)and normal glial cells(HEBs)is developed which simulates both mechanical and biological properties of human brain microenvironment in vivo through the investigation of the formulation of bioinks and optimization of printing process and parameters to study the effects of different concentration of gelatin(GA)within the bioink and different printing structures of the scaffold on the performance of the brain matrix-mimetic microenvironment models.The study provides experimental models for the exploration of the multiple factors in the brain microenvironment and scaffolds for GBM invasion study.

Adjunctive platelet-rich plasma and hyaluronic acid injection after arthroscopic debridement in Kellgren-Lawrence grade 3 and 4 knee osteoarthritis

BACKGROUND Osteoarthritis(OA)is the most common cause of pain and disability,predominantly affecting the knee.The current management of knee OA falls short of completely stopping disease progression,particularly in Kellgren-Lawrence(KL)grade 3 and 4 knee OA.As such,joint replacement is often recommended,although only 15%-33%of candidates accept it.Alternative therapeutic options are still needed to prevent the progression of joint damage and delay the need for knee arthroplasty.AIM To investigate the effect of adjunctive platelet rich plasma(PRP)and hyaluronic acid(HA)after arthroscopic debridement in KL grade 3 and 4 knee OA.METHODS This retrospective cohort study used the Western Ontario and McMaster Universities Osteoarthritis Index(WOMAC)score and WOMAC sub-scores(pain,stiffness,and function)to assess 21 patients,grouped according to medical record data of treatment received:Arthroscopic debridement(n=7);arthroscopic debridement with PRP(n=7);or arthroscopic debridement with HA(n=7).WOMAC scores and sub-scores at baseline and at 3 mo and 5 mo posttreatment were recorded.The three-group data were statistically analyzed using the tests of paired t,one-way analysis of variance,and post hoc least significant difference.RESULTS All three treatment groups showed significant improvements in WOMAC score and sub-scores from before treatment to 3 mo and 5 mo after treatment.However,the arthroscopic debridement with PRP treatment group,in particular,showed a significantly lower WOMAC pain score than the group who received arthroscopic debridement alone at 5 mo after the procedure(P=0.03).CONCLUSION Compared to arthroscopic debridement alone,adjunctive PRP after arthroscopic debridement significantly lessened the patients’pain symptom.

Detection of Serum Hyaluronic Acid and Laminin in Patients with Bladder Tumors

In order to investigate the changes of serum hyaluronic acid (HA) and laminin (LN) le-vels and their clinical implication in the patients with bladder tumors, the serum HA and LN levels in 34 patients with bladder tumor and 30 cases of control group were detected by radioimmunoassay before and after operation. The results showed that the serum HA and LN levels in the patients with bladder tumors were significantly higher than those in control group (P<0.01) before operation, and decreased significantly after operation (P<0.05). The serum levels of HA and LN in infiltration tumors were higher than those in superficial tumors (P<0.05). The serum HA and LN levels in patients with lymph node metastasis were higher than those without lymph node metastasis (P<0.01). The investigation revealed that HA and LN might be involved in the malignant biology behavior of bladder tumors and could be used as important markers of assistant diagnosis and condition monitoring.

BIOCHEMICAL STUDIES ON GLUCOAMINOGLYCANS CONTENT IN AFFECTED CARTILAGE HYALURONIC ACID LEVELS IN SERUM AND SYNOVIAL FLUID OF IDIOPATHIC FEMORAL HEAD NECROSIS

To investigate the role of cartilage alterations in the pathogenesis of the idiopathic femoral head necrosis, 3 components of glycosaminoglycans(GAG) in pathological and health cartilage, levels of hyaluronic acid(HA) in synovial fluid and serum were detected. The correlations among HA level in synovial fluid, serum and GAG content in cartilage were analyzed. The results showed that ①the three components of cartilage GAG in normal adults and children showed little difference; ②Compared with the normal autopsy specimens, steroid induced ANFH and Perthes disease specimens had significantly decreased GAG contents (P<0 025). In the former ones, sulfate radical content had no obvious reduction in Ficat Ⅱ (P>0 05), but it decreased significantly (P<0 05) in Ficat Ⅲ, while hexosamine decreased sharply in Ficat Ⅱ and had no marked alternation in Ficat Ⅲ. And hexuronic acid fell sharply during Ficat Ⅱ and Ficat Ⅲ (P<0 05). Serum level of HA did not have obvious changes until Ficat Ⅲ. HA level in synovial fluid decreased extremely in Ficat Ⅲ in contrast to Ficat Ⅱ and normal controls (P<0 05). Moreover, there was no correlation between levels of HA in serum and in synovial fluid (P>0 05); ③Children suffered from Perthes disease had a much higher level of HA in serum than the controls (P<0 01). HA level in serum led an inverse correlation with that in synovial fluid. (r=-0 663,P<0 05);④There was a positive correlation between HA level in synovial fluid and GAG content in both steroid induced ANFH and Perthes disease. GAG content was positive correlated with HA level in serum of Perthes disease, whereas, there was no correlation between them in steroid induced ANFH. The results suggest that:①GAG content in affected hip decreased significantly in the early stage. It provides clinical theory basis for auxiliary treatment to cartilage in early stage; ②Sulfate radical depletion is the most conspicuous one of GAG changes in middle and late stage. It suggests that the sulfate radical glycoaminoglycans should be replenished in these stages; ③Measurement of the serum HA level is of no value in early diagnosis of steroid induced ANFH. To some extent serum levels of HA reflect biochemical changes in cartilage in Perthes disease.

Preparation and Characterization of AlginateHyaluronic Acid-chitosan based Composite Gel Beads

The aim of this study was to fabricate composite gel beads based on natural polysaccharides. Hyaluronic acid（HA） and Chitosan（CS） were successfully admixed with Ca^2＋/alginate（SA） gel system to produce SA/HA/CS gel beads by dual crosslinking： the ionic gelation and the polyelectrolyte complexation. The preparation procedure was that the weight ratio of SA（2%, m/v） to HA（2%, m/v） was kept at 2：1, then the mixture was dripped into the Ca^2＋ solution for ion-crosslinking, and finally polyelectrolyte crosslinked with 2% low molecular weight CS（LMW-CS） for 1.5 hours. The optimal formulation was achieved by adjusting the concentration and the weight ratio of SA, HA and LMW-CS. Due to the incorporation of HA and LMWCS, the swelling ratio of the beads at pH 7.4 was increased up to 120, and the time for the maximum swelling degree was prolonged to 7.5 h. The swelling behavior was obviously improved compared to the pure SA/Ca^2＋ system. The preliminary results clearly suggest that the SA/HA/CS gel beads may be a potential candidate for biomedical delivery vehicles.

CHAP-Hyaluronic Acid (CHAP-HA) Filler as an Optimal Candidate for Forehead Filler Augmentation Using a 3-Point Injection Technique

Minimally invasive forehead augmentation is becoming increasingly popular in Asia. However, treatment of the glabella is associated with injection-related complications. The safety of injections can be increased through a thorough understanding of the anatomy and precise injection planes. The authors propose a 3-point injection technique for forehead augmentation in Asian patients that uses CHAP-hyaluronic acid (CHAP-HA) filler. The longevity of the filler was assessed using high-resolution ultrasound (HRU) imaging. Fifteen patients were examined using HRU before and immediately after treatment and at 1 month, 3 months, 6 months, and 12 months. As evident in HRU imaging, CHAP-HA remained visible within surrounding tissue for 6.4 ± 3.7 months. The mean Global Aesthetic Improvement Scale rating was 2.4 ± 0.5 immediately after treatment, 2.8 ± 0.3 at 1 month, 2.7 ± 0.5 at 3 months, 2.1 ± 0.6 at 6 months, and 1.5 ± 0.6 at 12 months. Minimal side effects were reported. The authors demonstrated that CHAP-HA filler may be an optimal candidate for forehead filler augmentation using a 3-point injection technique.

Intraarticular injections(corticosteroid, hyaluronic acid, platelet rich plasma) for the knee osteoarthritis

Osteoarthritis(OA)is a complex"whole joint"disease pursued by inflammatory mediators,rather than purely a process of"wear and tear".Besides cartilage degradation,synovitis,subchondral bone remodeling,degeneration of ligaments and menisci,and hypertrophy of the joint capsule take parts in the pathogenesis.Pain is the hallmark symptom of OA,but the extent to which structural pathology in OA contributes to the pain experience is still not well known.For the knee OA,intraarticular(IA)injection(corticosteroids,viscosupplements,blood-derived products)is preferred as the last nonoperative modality,if the other conservative treatment modalities are ineffective.IA corticosteroid injections provide short term reduction in OA pain and can be considered as an adjunct to core treatment for the relief of moderate to severe pain in people with OA.IA hyaluronic acid(HA)injections might have efficacy and might provide pain reduction in mild OA of knee up to 24 wk.But for HA injections,the costeffectiveness is an important concern that patients must be informed about the efficacy of these preparations.Although more high-quality evidence is needed,recent studies indicate that IA platelet rich plasma injections are promising for relieving pain,improving knee function and quality of life,especially in younger patients,and in mild OA cases.The current literature and our experience indicate that IA injections are safe and have positive effects for patient satisfaction.But,there is no data that any of the IA injections will cause osteophytes to regress or cartilage and meniscus to regenerate in patients with substantial and irreversible bone and cartilage damage.

Serum hyaluronic acid, procollagen type Ⅲ and Ⅳ in histological diagnosis of liver fibrosis

OBJECTIVE: To assess the significance of serum hyaluronic acid (HA), proeollagen type Ⅲ (PCⅢ), collagen type Ⅳ (CⅣ) in the histological diagnosis of liver fibrosis. METHODS: The concentrations of serum HA, PCⅢ, CⅣ in 253 patients with chronic liver diseases were measured by radioimmunoassay. Liver biopsies were performed in all patients at the same time. The liver was pathologically evaluated by a pathologist according to a scoring system. Combined with the results of liver pathological diagnosis, the accuracy of serum HA, PCⅢ, CⅣ in diagnosing patients with hepatic fibrosis (staging≥S_2) or cirrhosis (S_4) was assessed using the receiver operating curve (ROC). RESULTS: The cutoff values of serum HA, PCⅢ and CⅣ for identifying patients with hepatic fibrosis (≥S_2) or cirrhosis (S_4) were determined. The cutoff values of serum HA, PCⅢ and CⅣ for detecting patients with fibrosis (stage≥S_2) were 90μg/L, 90μg/L, 75μg/L, respectively; their sensitivity (Se) was 80.4%, 82%, 63.1%; their specificity (Spe) was 70.2%, 60.8%, 83.8%; their positive predictive values (PPV) were 86.7%, 83.5%, 90.4%; their negative predictive values (NPV) were 59.8%, 58.4%, 48.4%, respectively. The cutoff values for detecting patients with liver cirrhosis were 210μg/L for HA, 96.2% for Se, 85.3% for Spe, 65.4% for PPV, 98.8% for NPV; 150μg/L for PCⅢ, 76.4% for Se, 68.7% for Spe, 40.4% for PPV, 91.3% for NPV; 90μg/L for CⅣ, 80% for Se, 75.8% for Spe, 47.8% for PPV, 93.2% for NPV, respectively. CONCLUSIONS: Serum HA, PCⅢ and CⅣ can be determined for an accurate diagnosis of hepatic fibrosis in various stages. HA is the best for screening liver cirrhosis.

Influence of BOL on hyaluronic acid,laminin and hyperplasia in hepatofibrotic rats

AIM: To study the anti-hepatofibrosis mechanism of Bie Jia Jian oral liquid (BOL). METHODS: The model was induced by subcutaneous injection of CCl(4). BOL was administered and the change of serum hyaluronic acid (HA) and laminin (LN) was observed and the degeneration of liver cells and the degree of fibre hyperplasia analyzed. Changes of ultra micro-structure in liver cells were observed in some samples. RESULTS: HA was reduced in both the groups with low and high dosage of BOL, which showed a remarkable difference as compared with that of the model group (low dosage group: 376.15 microg/L+/-35.48 microg/L vs 806.07 microg/L+/-98.49 microg/L P【0.05; high dosage group: 340.14 microg/L+/-30.18 microg/L vs 806.07 microg/L+/-98.49 microg/L P【0.05). The LN content of low and high dosage group of BOL was lower than that of model group (low dosage group: 71.99 microg/L+/-8.15 microg/L vs 133.94 microg/L+/-14.45 microg/L P 【0.01; high dosage group: 71.68 microg/L+/-11.62 microg/L vs 133.94 microg/L+/-14.45 microg/L P【0.01) and colchicine group (low dosage group: 71.99 microg/L+/-8.15 microg/L vs 118.28 microg/L+/-16.13 microg/L P 【 0.05; high dosage group: 71.68 microg/L+/-11.62 microg/L vs 118.28 microg/L+/-16.13 microg/L P 【0.05). Examined by Ridit, BOL could reduce the degeneration and necrosis of liver cells (chi(2)=11.99 P【0.05), the degree of fibre hyperplasia (chi(2)=13.24 P【0.05) and the pathological change of ultra micro-structure as well. CONCLUSION: The BOL has certain therapeutic effect on the experiment hepatofibrosis. Its mechanisms might include: protecting the function of liver cells, inhibiting excessive synthesis and secretion of extracellular matrix from hepatic stellate cells, relieving the capillarization of hepatic sinusoid, improving liver micro-circulation, and regulating immune function.

Single-and double-dose of platelet-rich plasma versus hyaluronic acid for treatment of knee osteoarthritis: A randomized controlled trial

BACKGROUND Platelet-rich plasma(PRP)and hyaluronic acid have been shown to be useful in the treatment of knee osteoarthritis.However,investigations comparing the efficacy of these two drugs together are insufficient.AIM To compare the outcomes of PRP vs hyaluronic acid injections in three groups of patients with bilateral knee osteoarthritis.METHODS This randomized controlled trial study involved 95 patients.Thirty-one subjects received a single injection of PRP(group PRP-1),33 subjects received two injections of PRP at an interval of 3 wk(group PRP-2)and 31 subjects received three injections of hyaluronic acid at 1-wk intervals(group hyaluronic acid).The patients were investigated prospectively at the enrollment and at 4-,8-and 12-wk follow-up with the Western Ontario and McMaster Universities Arthritis Index(WOMAC)and Visual Analogue Scale questionnaires.RESULTS Percentages of patients experiencing at least a 30%decrease in the total score for the WOMAC pain subscale from baseline to wk 12 of the intervention were 86%,100%and 0%in the groups PRP-1,PRP-2 and hyaluronic acid,respectively(P<0.001).The mean total WOMAC scores for groups PRP-1,PRP-2 and hyaluronic acid at baseline were 63.71,61.57 and 63.11,respectively.The WOMAC scores were significantly improved at final follow-up to 42.5,35.32 and 57.26,respectively.The highest efficacy of PRP was observed in both groups at wk 4 with about 50%decrease in the symptoms compared with about 25%decrease for hyaluronic acid.Group PRP-2 had higher efficacy than group PRP-1.No major adverse effects were found during the study.CONCLUSION PRP is a safe and efficient therapeutic option for treatment of knee osteoarthritis.It was demonstrated to be significantly better than hyaluronic acid.We also found that the efficacy of PRP increases after multiple injections.

Noninvasive assessment of liver fibrosis with combined serum aminotransferase/platelet ratio index and hyaluronic acid in patients with chronic hepatitis B

AIM： To construct a noninvasive assessment model consisting of routine laboratory data to predict significant fibrosis and cirrhosis in patients with chronic hepatitis B （CHB）. METHODS： A total of 137 consecutive patients with CriB who underwent percutaneous liver biopsy were retrospectively analyzed. These patients were divided into two groups according to their aminotransferase （ALT） level. The sensitivity, specificity, positive predictive value （PPV）, negative predictive value （NPV）, the likelihood ratio （LR） of aminotransferase/platelet ratio index （APRI） ≥ 1.5 or 〈 1.5 in combination with different hyaluronic acid （HA） cut-off points were calculated for the presence of moderate to severe fibrosis/cirrhosis （fibrosis stages 2 and 4） and no to mild fibrosis/cirrhosis （fibrosis stages 0 and 1）. RESULTS： The APRI correlated with fibrosis stage in CriB patients. The APRI ≥1.5 in combination with a cut-off HA cut-off point 〉 300 ng/mL could detect moderate to severe fibrosis （stages 2-4） in Crib patients. The PPV was 93.7%, the specificity was 98.9%. The APRI 〈 1.5 in combination with different HA cut-off points could not detect no to mild fibrosis in CHB patients. CONCLUSION： The APRI ≥ 1.5 in combination with a HA cut-off point 〉 300 ng/mL can detect moderate to severe fibrosis （stages 2-4） in Crib patients.

Preparation and characterization of nanoparticles from quaternized cyclodextrin-grafted chitosan associated with hyaluronic acid for cosmetics

Hyaluronic acid(HA, 20–50 kDa) is a hydrophilic macromolecule with anti-wrinkle effects and moisturizing properties. However, its high molecular weight prevents it from penetrating into the deeper layers of the skin and, thus, limits its benefits to topical effects. Thus, the objective of this study is to prepare nanoparticles of quaternized cyclodextrin-grafted chitosan(QCD-g-CS) associated with HA in different molar ratios of QCD-g-CS and HA. The conjugation of the carboxylic moieties of HA and the amides of QCD-g-CS was confirmed by Fourier-transform infrared spectroscopy. Thus, the system was optimized to create nanoparticles with a small size(235.63 ± 21.89 nm), narrow polydispersity index(0.13 ± 0.02), and zeta potential of 16.07 ± 0.65 m V. The association efficiency and loading efficiency were determined by ultra-performance liquid chromatography as 86.77 ± 0.69% and 10.85 ± 0.09%, respectively. The spherical morphology of the obtained nanoparticles was confirmed by transmission electron microscopy. Moreover, the in-vitro hydrating ability was significantly higher( P < 0.001) than that of bulk HA(3.29 ± 0.41 and 1.71 ± 0.05 g water/g sample, respectively). The safety of these nanoparticles at concentrations in the range of 0.01–0.10 mg/ml was confirmed via tests on human skin fibroblasts. Together, these results demonstrate that the developed nanoparticles are promising for future applications in cosmetics.

SERUM CONCENTRATIONS OF HYALURONIC ACID, PROCOLLAGEN TYPE III NH_2-TERMINAL PEPTIDE, AND LAMININ IN PATIENTS WITH CHRONIC CONGESTIVE HEART FAILURE

Objective To explore the role of serum fibrotic indices including hyaluronic acid （HA）, procollagen type Ⅲ NH2-terminal peptide （PCIIIP）, and laminin （LN） in assessing the severity of myocardial fibrosis in chronic congestive heart failure （CHF）. Methods Serum levels of HA, PCIIIP, and LN in 39 patients with CHF E [14 with New York Heart Association （NYHA） functional class II, 21 with class Ⅲ, 4 with class Ⅳ] and in 46 patients with NYHA functional class I were assessed by radioimmunoassay. Results The serum concentrations of HA, PCMP, and LN were 359.75 ± 84.59 μg/L, 77.88 ± 24. 67 μg/L, 86. 73 ± 23.90 μg/L in CHF group, and 211.60 ±54. 80 μg/L, 64.82 ±23.99 μg/L, 82. 26 ±23.98 μg/L in NYHA functional class Ⅰ group, respectively. The HA level was significantly higher in CHF patients as compared with NYHA functional class Ⅰ group （ P 〈 0.05 ）. However, no difference was found in the levels of PCIIIP and LN between CHF group and NYHA functional class Ⅰ group. The serum HA concentration was negatively correlated with left ventricular ejection fraction （ r = - 0.71, P 〈 0.05 ）. Conclusion Serum HA level may act as an indicator for myocardial fibrosis.

Correlation Between Hyaluronic Acid,Hyaluronic Acid Synthase And Human Renal Clear Cell Carcinoma

Objective：To study the correlation between hyaluronic acid（HA）,hyaluronic acid synthase（HAS） and human renal clear cell carcinoma（RCCC）.Methods：The expression of three HAS isoforms＇ gene and HA in 93 RCCC tissues,27 nephridial tissues by the side of RCCC from two hospitals were measured with Real-Time RT-PCR、Western Blot and immunohistochemical methods and analyzed.Results：All RCCC and adjacent normal tissues expressed three HASs＇ mRNA protein;at the mRNA level,both RCCC and adjacent normal tissues,expressed more HAS3 than HAS1 or HAS2,their differences were statistically significant（all P values 0.05）;but,at the protein level,all HAS isoforms presented the equivalent expression.Compared with the adjacent non-neoplastic kidney tissues,the expression of all HAS isoforms＇ mRNA in RCCC tissues were increased evidently and their differences were significant（all P values 0.0001）;but at the protein level,only the expression of HAS3 increased evidently（P=0.022）.In all adjacent normal tissues,more than 80% renal tubular cells strongly expressed HA,however,only the minority RCCC cases（16/93） presented weakly positive HA staining in few cancer nests（5%-30%）,the difference were significant（P0.0001）.In RCCC tissues subgrouped according to clinical stage,pathological grade,lymphatic metastasis or not and distant metastasis or not,the HASs＇ mRNA protein differential expression all had no statistical significance（all P values 0.05）.Conclusion：Different from other malignancy,HA and HASs（except for HAS3） may not play important roles in the biological progress of human RCCC.

Preparation and Identification of Hyaluronic Acid From Fresh Pigskin

Hyaluronic acid （HA） had been prepared from pigskin residues with neutral proteinase. The preparing results and conditions were studied. After extracting and purification, HA was detected through ultraviolet spectra and infraction spectrum, and its content and purity were tested by carbazole and Elason-Morgan, respectively. This results indicated that significant quantities of HA could be prepared in fresh pigskin with biologic enzyme, and the pure HA was cosmetic grade and food grade.

Preparation and Kinetics of a Novel Glutathione Peroxidase Mimic——Selenium-modified Hyaluronic Acid

A selenium-modified hyaluronic acid（HA） compound（SeHA） was synthesized as a mimic of glutathione peroxidase（GPX）. IR and NMR spectra of SeHA predict that the --CH2OH group of the N-acetyl-D-glucosamine in HA was modified by group --Sell. There are averagely 152 --Sell groups in one SeHA molecule. The GPX activities are 103.88, 32. 15 and 152. 71 U/μmol, respectively, when the substrates were H2O2, BuOOH and CuOOH. Ping-pong mechanism was observed in the steady-state kinetic studies of the reactive oxygen species（ROS） consuming reaction. Result of reactions of SeHA with free radical capturer 2,6-di-tert-butyl-4-methylphenol（BHT） shows that the catalysis is based on a non-free radical-mechanism and the SeHA can not be inhibited by iodoacetate, an enzyme inhibitor.