Low Molecular Weight Hyaluronic Acid Research Articles

Hyaluronic Acid Oligomer Immobilization as an Angiogenic Trigger for the Neovascularization of TE Constructs.

Tissue engineered (TE) substitutes of clinically relevant sizes need an adequate vascular system to ensure function and proper tissue integration after implantation. However, the predictable vascularization of TE substitutes is yet to be achieved. Molecular weight variations in hyaluronic acid (HA) have been pointed to trigger angiogenesis. Thus, this study investigates HA oligomer immobilization as a promoter for TE construct vascularization. As a proof-of-concept, the surface of methacrylated gelatin (GelMA) hydrogels were functionalized with high molecular weight (HMW; 1.5 to 1.8 MDa) and low molecular weight (LMW; < 10 kDa) HA, previously modified with aldehyde groups to enable the immobilization through Schiff's base formation. The ability of A-HA to bind amine-presenting surfaces was confirmed by Surface Plasmon Resonance (SPR). Human Umbilical Vein Endothelial Cells (HUVECs) seeded over hydrogels functionalized with LMW HA showed higher proliferation and expression of angiogenic markers (KDR and CD31), than those grown in HMW HA conjugated- or plain surfaces, in line with the activation of HA ERK1/2 mediated downstream signaling. Moreover, when cocultured with human dental pulp cells (hDPCs) encapsulated into the GelMA, an increase in endothelial cell migration was observed for the LMW HA functionalized formulations. Overall LMW HA functionalization enhanced endothelial cell response showing potential as an angiogenesis inducer for TE applications.

Stringiness of hyaluronic acid emulsions.

ObjectiveCosmetic emulsions containing hyaluronic acid are ubiquitous in the cosmetic industry. However, the addition of (different molecular weight) hyaluronic acid can affect the filament stretching properties of concentrated emulsions. This property is often related to the “stringiness” of an emulsion, which can affect the consumer's choice for a product. It is thus very important to investigate and predict the effect of hyaluronic acid on the filament stretching properties of cosmetic emulsions.MethodsModel emulsions and emulsions with low and high molecular weights are prepared and their filament stretching properties are studied by the use of an extensional rheometer. Two different stretching speeds are employed during the stretching of the emulsions, a low speed at 10 µm/s and a high speed at 10 mm/s. The shear rheology of the samples is measured by rotational rheology.ResultsWe find that filament formation only occurs at high stretching speeds when the emulsion contains high molecular weight hyaluronic acid. The formation of this filament, which happens at intermediate states of the break‐up, coincides with an exponential decay in the break‐up dynamics. The beginning and end of the break‐up of high molecular weight hyaluronic acid emulsions show a power law behaviour, where the exponent depends on the initial stretching rate. At a lower stretching speed, no filament is observed for both high molecular weight and low molecular weight hyaluronic acid emulsions and the model emulsion. The emulsions show a power law behaviour over the whole break‐up range, where the exponent also depends on the stretching rate. No significant difference is observed between the shear flow properties of the emulsions containing different molecular weights hyaluronic acid.ConclusionIn this work, we underline the importance of the molecular weight of hyaluronic acid on the elongational properties of concentrated emulsions. The filament formation properties, for example the stringiness, of an emulsion is a key determinant of a product liking and repeat purchase. Here, we find that high molecular weight hyaluronic acid and a high stretching speed are the control parameters affecting the filament formation of an emulsion.

Rheological Properties of Hyaluronic Acid Diluted Solutions as Components of Cosmetics

Rheological measurements were carried out on dilute aqueous solutions of high (HMW-HA, 1150 kDa) and low molecular weight hyaluronic acids (LMW-HA, 8 kDa) along with their mixtures to determine the relationship between the viscosity and concentration of the samples. Molecular weight and polydispersity of low molecular HA have been determined by matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS). HA diluted solutions were found to be weakly structured liquids with a slight viscosity anomaly. Critical values of concentration were determined at different ratios of HMW-HA and LMW-HA, leading to a sharp increase in the viscosity of solutions. Rheological studies have proved the pseudoplastic nature of the viscous flow of HMW-HA solutions. The possibility of using the Ostwald-de Waele equation for the mathematical description of a viscous flow was established. The results of the rheological analysis might be applied for the rational development of cosmetic formulations containing hyaluronic acid of various molecular weights.

Downregulation of Hyaluronic acid-CD44 signaling pathway in cervical cancer cell by natural polyphenols Plumbagin, Pongapin and Karanjin.

Hyaluronic acid (HA)-CD44 pathway showed association with several malignancies. The natural polyphenols Plumbagin, Pongapin and Karanjin showed anti-cancer activities in different tumors including cervical carcinoma. To understand their mechanism of anti-cancer activity, the effect of the compounds on HA-CD44 pathway was analyzed in cervical cancer cell line HeLa. The mRNA expression of three different isoforms of CD44 i.e., CD44s, CD44v3, and CD44v6, was differentially downregulated by the compounds. This was validated by Western blot and immunocytochemical analysis of CD44s.The low molecular weight HA (LMW-HA) showed growth promoting activity in HeLa at low concentration, whereas high molecular weight HA (HMW-HA) had no such effect. The compounds could preferentially downregulate the LMW-HA level in HeLa, as evident in the cell as well as in the cell-free conditioned medium. Concentration-dependent upregulation of HA synthase-2 (HAS2) was seen in the cell by the compounds, whereas differential downregulation of hyalurinidases 1-4 (HYAL 1-4), predominantly HYAL1, were seen. The compounds could also downregulate the downstream target of the pathway p-AKT (T-308) in concentration-dependent manner. Thus, the compounds could attenuate the HA-CD44 pathway in HeLa cell to restrict the tumor growth.

Enhancement of T2* Weighted MRI Imaging Sensitivity of U87MG Glioblastoma Cells Using γ-Ray Irradiated Low Molecular Weight Hyaluronic Acid-Conjugated Iron Nanoparticles.

IntroductionIt has been reported that low-molecular-weight hyaluronic acid (LMWHA) exhibits a potentially beneficial effect on cancer therapy through targeting of CD44 receptors on tumor cell surfaces. However, its applicability towards tumor detection is still unclear. In this regard, LMWHA-conjugated iron (Fe3O4) nanoparticles (LMWHA-IONPs) were prepared in order to evaluate its application for enhancing the T2* weighted MRI imaging sensitivity for tumor detection.MethodsLMWHA and Fe3O4 NPs were produced using γ-ray irradiation and chemical co-precipitation methods, respectively. First, LMWHA-conjugated FITC was prepared to confirm the ability of LMWHA to target U87MG cells using fluorescence microscopy. The hydrodynamic size distribution and dispersion of the IONPs and prepared LMWHA-IONPs were analyzed using dynamic light scattering (DLS). In addition, cell viability assays were performed to examine the biocompatibility of LMWHA and LMWHA-IONPs toward U87MG human glioblastoma and NIH3T3 fibroblast cell lines. The ability of LMWHA-IONPs to target tumor cells was confirmed by detecting iron (Fe) ion content using the thiocyanate method. Finally, time-of-flight secondary ion mass spectrometry (TOF-SIMS) imaging and in vitro magnetic resonance imaging (MRI) were performed to confirm the contrast enhancement effect of LMWHA-IONPs.ResultsFlorescence analysis results showed that LMWHA-FITC successfully targeted the surfaces of both tested cell types. The ability of LMWHA to target U87MG cells was higher than for NIH3T3 cells. Cell viability experiments showed that the fabricated LMWHA-IONPs possessed good biocompatibility for both cell lines. After co-culturing test cells with the LMWHA-IONPs, detected Fe ion content in the U87MG cells was much higher than that of the NIH3T3 cells in both thiocyanate assays and TOF-SIMs images. Finally, the addition of LMWHA-IONPs to the U87MG cells resulted in an obvious improvement in T2* weighted MR image contrast compared to control NIH3T3 cells.DiscussionOverall, the present results suggest that LMWHA-IONPs fabricated in this study provide an effective MRI contrast agent for improving the diagnosis of early stage glioblastoma in MRI examinations.

Estimation of the Effect of Accelerating New Bone Formation of High and Low Molecular Weight Hyaluronic Acid Hybrid: An Animal Study.

Osteoconduction is an important consideration for fabricating bio-active materials for bone regeneration. For years, hydroxyapatite and β-calcium triphosphate (β-TCP) have been used to develop bone grafts for treating bone defects. However, this material can be difficult to handle due to filling material sagging. High molecular weight hyaluronic acid (H-HA) can be used as a carrier to address this problem and improve operability. However, the effect of H-HA on bone formation is still controversial. In this study, low molecular weight hyaluronic acid (L-HA) was fabricated using gamma-ray irradiation. The viscoelastic properties and chemical structure of the fabricated hybrids were evaluated by a rheological analysis nuclear magnetic resonance (NMR) spectrum. The L-MH was mixed with H-HA to produce H-HA/L-HA hybrids at ratios of 80:20, 50:50 and 20:80 (w/w). These HA hybrids were then combined with hydroxyapatite and β-TCP to create a novel bone graft composite. For animal study, artificial bone defects were prepared in rabbit femurs. After 12 weeks of healing, the rabbits were scarified, and the healing statuses were observed and evaluated through micro-computer tomography (CT) and tissue histological images. Our viscoelastic analysis showed that an HA hybrid consisting 20% H-HA is sufficient to maintain elasticity; however, the addition of L-HA dramatically decreases the dynamic viscosity of the HA hybrid. Micro-CT images showed that the new bone formations in the rabbit femur defect model treated with 50% and 80% L-HA were 1.47 (p < 0.05) and 2.26 (p < 0.01) times higher than samples filled with HA free bone graft. In addition, a similar tendency was observed in the results of HE staining. These results lead us to suggest that the material with an H-HA/L-HA ratio of 50:50 exhibited acceptable viscosity and significant new bone formation. Thus, it is reasonable to suggest that it may be a potential candidate to serve as a supporting system for improving the operability of granular bone grafts and enhancing new bone formations.

Zn-MOF Encapsulated Antibacterial and Degradable Microneedles Array for Promoting Wound Healing.

An infected skin wound caused by external injury remains a serious challenge in clinical practice. Wound dressings with the properties of antibacterial activity and potent regeneration capacity are highly desirable for wound healing. In this paper, a degradable, ductile, and wound-friendly Zn-MOF encapsulated methacrylated hyaluronic acid (MeHA) microneedles (MNs) array is fabricated through the molding method for promoting wound healing. Due to the damage capability against the bacteria capsule and oxidative stress of the zinc ion released from the Zn-MOF, such MNs array presents excellent antibacterial activity, as well as considerable biocompatibility. Besides, the degradable MNs array composed of photo-crosslinked MeHA possesses the superior capabilities to continuously and steadily release the loaded active ingredients and avoid secondary damage to the wound. Moreover, the low molecular weight hyaluronic acid (HA) generated by hydrolysis of MeHA is also conducive to tissue regeneration. Benefiting from these features, it has been demonstrated that the Zn-MOF encapsulated degradable MNs array can dramatically accelerate epithelial regeneration and neovascularization. These results indicate that the combination of MOFs and degradable MNs array is of great value for promoting wound healing.

Discoordination of the processes of activation and suppression of immunocompetent cells during mesotherapy with hyaluronic acid

Objective. The study aimed to assess the dynamics of the systemic immune response in patients during mesotherapy with hyaluronic acid (HA).Materials and methods. The observation group included 26 women who received the first-time mesocorrection with drugs based on hyaluronic acid (HA). Injections of low molecular weight HA were carried out according to standard methods in a course of 5 procedures with an interval of 14 days. The parameters of the innate and adaptive immune response were studied before and two weeks after the end of the course. The skin condition was assessed by dermatoscopy (Aramo Smart Lite 300, Southern Korea).Results. The clinical effect of the course of procedures was reflected in the subjective improvement in the appearance. The improvement was confirmed by hardware analysis, which recorded an increase in hydration, a smoothing of the skin relief, and a decrease in the depth of wrinkles. At the end of the course, redistribution of lymphocyte populations towards natural killer cells and B-lymphocytes was revealed with a decrease in the total number of T cells. The antibody production of immunoglobulins of classes M and G was increased, the serum content of Ig A and IgE was reduced, the number of both T-effectors and T-lymphocytes with immunosuppressive activity increased. Changes in the neutrophil system were characterized by the inhibition of the production of reactive oxygen intermediates; the dynamics of the expression of Toll-like receptors by monocytes was ambiguous.Conclusion. The results of the study confirmed the active involvement of the factors of innate and adaptive systemic response in the cosmetic effect, which manifested itself immediately after mesotherapy as systemic dysregulatory immune changes.

Low Molecular-weight Hyaluronic Acid Versus Physiotherapy for the Treatment of Supraspinatus Tendinopathy: A Randomized Comparative Clinical Trial.

The tendons of the rotator cuff are major sources of shoulder pain. This study aimed to compare the effects of low molecular-weight hyaluronic acid with physiotherapy (PT) in patients with supraspinatus tendinopathy (ST). We carried out a parallel two-group randomized comparative clinical trial in an outpatient clinic of physical medicine and rehabilitation at a teaching hospital. In total, 51 patients (31 women) aged 20 to 55 years with ST were randomly allocated to subacromial hyaluronate injection (n = 28) and PT (n = 23) groups. For the hyaluronate group, we administered a single injection of 2 mL (20 mg) hyaluronate 1% (500 to 700 kDa). For PT, we prescribed three sessions of treatment per week for 12 weeks, totaling 36 sessions including rotator cuff activation exercises. The primary outcome was shoulder pain in the visual analog scale. The secondary outcomes included the range of movement and the disability score of the shoulder, and a World Health Organization questionnaire on quality of life. We did the measurements at the baseline and at one, four, and 12 weeks after intervention. The results showed that both interventions were beneficial in the management of ST. However, hyaluronate was more effective in reducing shoulder pain at rest and during activities (both P < 0.001, effect size = 0.52 and 0.68, respectively). The two interventions similarly decreased patients' disability (P = 0.196). Hyaluronate improved shoulder motion and the quality of life better than PT. In the treatment of ST, low molecular-weight hyaluronate is more effective than PT, at least for three months. Particularly, hyaluronate is more successful in alleviating pain.

Effects of low and high molecular weight hyaluronic acid on the osteoarthritic temporomandibular joint in rabbit.

To compare the effect between intra-articular infiltration of low molecular weight (LMW-HA) and high molecular weight hyaluronic acid (HMW-HA) on the histopathological characteristics of the cartilage and disc of the temporomandibular joint (TMJ) osteoarthritis (OA) induced in rabbits. An experimental study was conducted on 38 rabbit TMJs. The effect of different hyaluronic acids was compared at 30 and 135days. Histopathological analysis was performed. Cartilage damage was assessed with the OARSI scale. The severity of the induced OA according to OARSI was 3.4 degrees in the mandibular condyle (MC) and 3.2 in the mandibular fossa (MF); the articular disc (AD) presented disorganization of the collagen fibers, with randomly arranged hypertrophic chondrocytes. At 30days, untreated TMJs worsened. TMJ treated with LMW-HA reduced its severity to 1.5 degrees in MC and 1.6 in MF, the AD presented histological aspects within normal limits. TMJ treated with HMW-HA presented 2.4 degrees in MC and 2.2 in MF, the AD maintained characteristics similar to the group with OA. At 135days, all groups worsened. Exogenous HA is effective in the management of TMJ-OA induced in rabbits, showing cartilage and articular disc repair at 30days. The LMW-HA group had better effects on joint tissue than HMW-HA 30days after treatment. However, at 135days, both groups presented regression of joint tissue repair. HA is effective in the anti-arthritic treatment of TMJ-OA induced in rabbits; LMW-HA shows better results in cartilage and articular disc repair than HMW-HA.

Comparison of three treatment protocols with intra-articular low or intermediate molecular weight hyaluronic acid in early symptomatic knee osteoarthritis.

Introduction:Viscosupplementation with hyaluronic acid (HA) is indicated for non-responders to non-pharmacological therapy, to analgesics or when non-steroidal anti-inflammatory drugs (NSAIDs) are contraindicated. The aim of this study is to compare the efficacy, safety and costs of three different HA treatments (Sinovial® Forte, sinovial one and hyalgan).Patients and methods:Ninety patients with grade I/II Kellgren–Lawrence knee osteoarthritis were included in three groups, the first was treated with hyalgan (weekly for 5 weeks), the second with Sinovial® Forte (weekly for 3 weeks) and the third group with a single injection of sinovial one.Results:All three treatments were effective, with an average reduction in the Western Ontario and McMaster Universities osteoarthritis index (WOMAC) score of 18.9 points for hyalgan, 18.04 points for Sinovial® Forte and 17.92 points for sinovial one. The comparison of the three groups did not show any statistical difference in terms of efficacy. National health system (NHS) and social costs are, respectively, €419.12 and €853.43 for hyalgan, €338.64 and €599.22 for Sinovial® Forte, €221.56 and €308.42 for sinovial one.Conclusion:All three treatments were equally effective with no statistically significant differences; thus, the treatment with sinovial one may be considered as clinically effective as the other two regimens, but with a very efficient cost profile in early symptomatic knee osteoarthritis.

A modular, injectable, non-covalently assembled hydrogel system features widescale tunable degradability for controlled release and tissue integration

Biomaterials with attenuated adverse host tissue reactions, and meanwhile, combining biocompatibility with mimicry of mechanical and biochemical cues of native extracellular matrices (ECM) to promote integration and regeneration of tissues are important for many biomedical applications. Further, the materials should also be tailorable to feature desired application-related functions, like tunable degradability, injectability, or controlled release of bioactive molecules. Herein, a non-covalently assembled, injectable hydrogel system based on oligopeptides interacting with sulphated polysaccharides is reported, showing high tolerability and biocompatibility in immunocompetent hairless mice. Altering the peptide or polysaccharide component considerably varies the in vivo degradation rate of the hydrogels, ranging from a half-life of three weeks to no detectable degradation after three months. The hydrogel with sulphated low molecular weight hyaluronic acid exhibits sustained degradation-mediated release of heparin-binding molecules in vivo, as shown by small animal magnetic resonance imaging and fluorescence imaging, and enhances the expression of vascular endothelial growth factor in hydrogel surrounding. In vitro investigations indicate that M2-macrophages could be responsible for the moderate difference in pro-angiogenic effects. The ECM-mimetic and injectable hydrogels represent tunable bioactive scaffolds for tissue engineering, also enabling controlled release of heparin-binding signalling molecules including many growth factors.

Efficacy and safety of a cosmeceutical regimen based on a combination of low molecular weight hyaluronic acid, placental peptides and extract of Malus domestica in improving signs of periorbital skin aging

Background: Periorbital wrinkle formation is a relatively early sign of skin aging. The public interest in the reversal of aging has increased significantly among demanding patients and aesthetic practitioners within the past decades. However, many aesthetic patients, whether young or old, prefer to avoid invasive procedures wherever possible, seeking natural-looking results.Therefore, physicians have had to respond to their patient's expectations. Objectives: This study aimed to evaluate whether the synergistic anti-aging activity of MF3 Placenta 3R serum product has an influence towards the treating of wrinkles as well as skin hydration, and skin elasticity in the periorbital area. Methods: 23 healthy adult female volunteers were instructed to apply MF3 Placenta 3R serum containing a mixture of low molecular weight hyaluronic acid (LMWHA), placental peptides and extract of Malus domestica around the eye area twice daily during the study period of eight weeks. The skin measurements were performed in the periorbital area by investigating the skin elasticity (Cutometer) and skin hydration (Corneometer). Patients questionnaires were answered at 59 days. Results: The findings of the study proved a moisturizing impact of MF3 Placenta 3R serum throughout the trial that transformed into significant improvements in periocular skin hydration and elasticity. Conclusion: The tested formulation of MF3 Placenta 3R serum appears to be effective and may stimulate the periorbital skin rejuvenation in a women 44 – 52 years, resulting in the clinical appearance of smoother skin with less visible wrinkling. Further randomized, controlled studies have to be done to confirm these results.

Comparing the efficacy of hyaluronic acid products with various molecular weights as mono and combined with chondroitin sulfate regimens in treatment of patients with stage I–III knee osteoarthritis

Aim: to evaluate the effectiveness of hyaluronic acid (HA) preparations with different molecular weights and in combination with chondroitin sulfate (HS) for intra-articular (IA) injections in the treatment of patients with stage I–III knee OA.Subjects and methods. IA HA injections were performed 160 patients with primary and post-traumatic knee OA of the I–III stages at the department of traumatology-orthopedics, V.A. Nasonova Research Institute of Rheumatology for the period from September 2017 to June 2019. Patients were divided into 4 groups. Group 1 consisted of 80 patients treated with low molecular weight (LMW) HA, group 2–20 patients treated with medium molecular weight (MMW) HA, group 3–30 patients treated with high molecular weight (HMW) HA, and group 4–30 patients who were intraarticular introduced HA with HS. The course of IA injections was 2 for LMW, HMW, and HA with HS, and 3 for MMW HA. Injections were performed with an interval of 1 week. To evaluate the results of treatment, we studied the intensity of pain according to VAS and the total score of KOOS before treatment and on follow-up examinations 1, 3 and 6 months after the course of IA HA injections.Results. The maximum reduction in pain with IA HA injections at stage I of knee OA occurred by 3 months after the course of treatment. Moreover, improvement was detected by 1 month in 84.3% of cases, and remained until the end of the study in 71.1% of patients. All HA preparations used in stage I of knee OA were effective. At stage II of the knee OA after 3 months after the course of IA HA, different efficiencies of HA preparations were revealed. So, in the groups of LMW, MMW and HA with HS, the improvement persisted up to 3 months, and in the group of HMW HA – up to 1 month. After 3 months, the best results were shown by HA with HS, by 6 months the results were comparable. IA HA injections at the II stage of knee OA led to good and excellent results 1 month after the course of treatment in 53.9% of cases, but by the end of the study, improvement remained in only 30.8% of patients. In the case of the use of HA in stage III of the knee OA, the effectiveness of the studied drugs was comparable, and the maximum improvement was achieved by 1 month. The positive effect of IA HA injections in patients with stage III of the knee OA one month after the course of treatment was obtained in 40.6% of cases, by 3 months it decreased to 18.8%, and by 6 months – to 15.7% of patients.Conclusions. IA injections of HA at stage I of the knee OA is a highly effective method of conservative treatment, which allows to relieve pain and improve the condition of the knee joint for a period of 6 months or more. The use of HA preparations at stage II of the knee OA allows reducing pain up to 3 months with IA injections of LMW and MMW HA, as well as HA with HS. HMW HA helps reduce pain intensity for a period of 1 month. The use of HA preparations in stage III of the knee OA leads to a short-term relief of symptoms of OA.

Bioactive hyaluronic acid fragments inhibit lipopolysaccharide-induced inflammatory responses via the Toll-like receptor 4 signaling pathway

The high- and the low-molecular weight hyaluronic acids (HMW-HA and LMW-HA, respectively) showed different biological activities in inflammation. However, the role of LMW-HA in inflammatory response is controversial. In this study, we aimed to investigate the effect of bioactive hyaluronan (B-HA) on lipopolysaccharide (LPS)-induced inflammatory responses in human macrophages and mice. B-HA was produced from HA treated with glycosylated recombinant human hyaluronidase PH20. Human THP-1 cells were induced to differentiate into macrophages. THP-1-derived macrophages were treated with B-HA, LPS, or B-HA + LPS. The mRNA expression and the production of inflammatory cytokines were determined using quantitative real-time PCR and enzyme-linked immunosorbent assay. The phosphorylation levels of proteins in the nuclear factor-κB (NF-κB), mitogen-activated protein kinase (MAPK), and IRF-3 signaling pathways were measured using Western blot. The in vivo efficacy of B-HA was assessed in a mouse model of LPS-induced inflammation. Results showed that B-HA inhibited the expression of TNF-α, IL-6, IL-1, and IFN-β, and enhanced the expression of the antiinflammatory cytokine IL-10 in LPS-induced inflammatory responses in THP-1-derived macrophages and in vivo. B-HA significantly suppressed the phosphorylation of the TLR4 signaling pathway proteins p65, IKKα/β, IκBα, JNK1/2, ERK1/2, p38, and IRF-3. In conclusion, our results demonstrated that the B-HA attenuated the LPS-stimulated inflammatory response by inhibiting the activation of the TLR4 signaling pathway. B-HA could be a potential anti-inflammatory drug in the treatment of inflammatory disease.

High molecular weight form of hyaluronic acid reduces neuroinflammatory response in injured sciatic nerve via the intracellular domain of CD44.

Inflammatory response after peripheral nerve injury is required for clearance of tissue debris and effective regeneration. Studies have revealed that hyaluronic acid (HA) may exert different properties depending on their molecular size. High molecular weight HA (>>1,000 kDa; HMW-HA) displays immunosuppressive properties, whereas low molecular weight HA (<800 kDa; LMW-HA) induces proinflammatory responses. The role of HMW-HA interaction with CD44, a major HA receptor, in neuroinflammatory responses has not been fully elucidated. The purpose of this experimental study was to investigate the effects of topical applications of HMW-HA on the sciatic nerve injury in an adult rat model. At the crush site on the sciatic nerve, the recordings of compound muscle action potential (CMAP) and the levels of several proteins related to inflammatory response were assessed at time intervals of 2, 4, and 6 weeks postsurgery. Here, we show that the recovery effect of HMW-HA treatment had significantly shortened latency and increased amplitude of CMAP compared with crushed alone, crushed plus γ-secretase inhibitor with or without HA treatment at 6 weeks after surgery. Our data reveal that HMW-HA could downregulate the expression of IL1-β, TLR4, and MMP-9, whereas these proteins expression were increased when the CD44-ICD activity was inhibited using γ-secretase inhibitor. Our findings demonstrated a novel role of CD44-ICD in HA-mediated recovery of peripheral nerve injury. Clinical relevance: an alternative for the regeneration of peripheral nerve injury.

Efficacy of single high-molecular-weight versus triple low-molecular-weight hyaluronic acid intra-articular injection among knee osteoarthritis patients

BackgroundTo compare intra-articular (IA) knee injections of a cross-linked high-molecular-weight hyaluronic acid (HMW-HA) with a linear low-molecular weight HA (LMW-HA) in terms of pain and functional improvement among knee osteoarthritis (OA) patients.MethodsIn this single-blinded RCT, the patients were randomly divided into two groups for HA injections. The first group received an HMW-HA (Arthromac) injection, while the other received three weekly LMW-HA (Hyalgan) injections. Pain and function were assessed using the outcome measures including WOMAC, Lequesne and VAS indices, once prior to injection, as well as 2 and 6 months after injections.ResultsA total of 90 patients were included. There was no significant difference in baseline characteristics including age and sex between the two groups. Our analysis showed that total WOMAC, Lequesne and VAS mean scores remarkably improved at both follow-up time-points compared to the baseline measurements (p < 0.001). There was no significant superiority between the two therapeutic protocols according to our outcome measures at any time-point of follow-up. The only except was about the improvement in WOMAC stiffness subscale that was significantly higher in LMW-HA group compared to HMW-HA (p = 0.021). Moreover, no significant difference was observed in minor complications and injection-induced pain scores between the two groups.ConclusionThis study proved that a single HMW-HA injection is as effective as multiple injections of LMW-HA counterparts in periods of 2 and 6 months follow-up.This study protocol was registered in Iranian database of RCTs (IRCT; www.irct.ir) with the trial registration number IRCT20130523013442N24 and registration date 2018-07-13.

Corrigendum to "Novel Hybrid Gels Made of High and Low Molecular Weight Hyaluronic Acid Induce Proliferation and Reduce Inflammation in an Osteoarthritis In Vitro Model Based on Human Synoviocytes and Chondrocytes".

[This corrects the article DOI: 10.1155/2019/4328219.].

The matrix of SDS integrated with linear hydrophilic polymer for resolution of high- and low-molecular weight hyaluronic acids in MEKC

Membranous nephropathy (MN) is the most common cause of nephrotic syndrome in adults, when not effectively treated. The aim of this study was to discover new targets for the diagnosis and treatment of MN. A reliable mouse model of MN was used by the administration of cationic bovine serum albumin (cBSA). Mice with MN exhibited proteinuria, histopathological changes, and accumulation of immune complexes in the glomerular basement membrane. Label-free proteomics analysis was performed to identify changes in protein expression, and the overexpressed proteins were evaluated. There were 273 proteins that showed significantly different expression in mice with MN, as compared to the controls. String analysis showed that functions related to cellular catabolic processes were downregulated in MN. Among the differentially expressed proteins, prohibitin 1 (PHB1) and prohibitin 2 (PHB2) were upregulated in the kidneys of mice with MN, as demonstrated by immunohistochemistry (IHC), and this upregulation was observed in both the tubular cells and glomeruli. Both shRNA-mediated knockdown of PHB1 or PHB2 inhibited tumor suppressor p53 expression and significantly promoted podocyte proliferation. In addition, both PHB1 and PHB2 were responsible for cBSA-induced cytotoxicity. Microarray analysis further revealed that the upregulation of PHB1 and PHB2 may be due to a blockage of proteasome activity. These data demonstrate that the upregulation of PHB2 is involved in cBSA-mediated podocyte cytotoxicity, which may lead to MN development. © 2019

Impact of a low molecular weight hyaluronic acid derivative on contact lens wettability

PurposeTo investigate the interaction of a novel low molecular weight hyaluronic acid derivative containing hydrophobic groups with soft contact lenses and its effect on lens hydrophilicity compared with a conventional form of hyaluronic acid. MethodsThis investigation studied the uptake of fluorescently-labelled hyaluronic acid and a low molecular weight hyaluronic acid derivative to four types of contact lenses using fluorescent microscopy and confocal laser scanning microscopy. Further, the four lens types were used to compare efficacy in improving hydrophilicity, as well as maintenance of contact angle measurements, in commercially available multipurpose solutions that contained either hyaluronic acid, the low molecular weight hyaluronic acid derivative, or an alternative wetting agent. ResultsThe low molecular weight hyaluronic acid derivative was found to sorb more readily to silicone hydrogel lenses and exhibit a greater accumulation over time than conventional hyaluronic acid. Multipurpose solutions containing the low molecular weight hyaluronic acid derivative showed an increase in lens hydrophilicity through decreases in contact angle measurements when compared with those obtained from lenses treated with multipurpose solutions containing conventional hyaluronic acid or alternative wetting agents. This increase in lens hydrophilicity associated with the low molecular weight hyaluronic acid derivative was also maintained over multiple cycles in phosphate buffered saline, while alternative solutions with conventional hyaluronic acid did not. ConclusionOverall, lens treatment using a low molecular weight hyaluronic acid derivative-based solution lead to improved in vitro lens hydrophilicity.