Termo de consentimento livre e esclarecido e sua relação com os procedimentos de preenchimento labial / Free and informed consent terms and its relationship with lip filling procedures

Introdução: Na medida em que envelhecemos os lábios estreitam-se, ocasionando perda de volume e contorno e como forma de minimizar este efeito fisiológico o preenchimento labial de escolha utilizado é o ácido hialurônico. É possível perceber efeitos adversos advindos do emprego deste material, e pelo fato da informação ao paciente ser assegurada pelo Código de Defesa do Consumidor e pelo fato da necessidade dos Cirurgiões-Dentistas terem de esclarecer seus pacientes, o Termo de Consentimento Livre e Esclarecido tornase necessário. Objetivo: identificar, por meio de aplicação de questionário, a percepção de profissionais que trabalham com Harmonização Orofacial em relação a necessidade do emprego do Termo de Consentimento Livre e Esclarecido (TCLE). O questionário apresentou 6 perguntas objetivas, que foram disponibilizadas na plataforma Google Forms®. Material e Método: os dados obtidos foram tabulados em uma planilha eletrônica do programa Microsoft Excel e após analisados descritivamente através de tabelas de frequência, porcentagens e gráficos estatísticos. Resultados: dentre os entrevistados foi constatado que a maioria, 87,5% dos especialistas em Harmonização Orofacial realizam o procedimento de preenchimento labial em sua rotina clínica, e 12,5% não. Conclusão: no presente estudo identificamos que os especialistas realizam o emprego do TCLE, em sua maioria, porém, alguns destes ainda negligenciam o seu uso(AU)

Introduction: As we age, the lips become thinner and to minimize this effect, the lip filler used is hyaluronic acid. It is possible to notice adverse effects arising from the use of this material, and it is extremely important that Dental Surgeons have to clarify their patients, the Free and Informed Consent Form becomes necessary. Objective: to identify, through the application of a questionnaire, the perception of professionals who work with Orofacial Harmonization in relation to the need to use the Free and Informed Consent Form (TCLE). The questionnaire presented 6 objective questions, which were made available on the Google Forms® platform. Materials and Methods: the data obtained were tabulated in a Microsoft Excel spreadsheet and then analyzed descriptively using frequency tables, percentages and graphs. Results: among those interviewed, it was found that the majority, 87.5% of specialists in Orofacial Harmonization perform the lip filling procedure in their clinical routine, and 12.5% do not. With the high percentage of 59.4%, it was possible to verify that the majority of professionals perform 1 to 3 procedures per month; 31.3% perform 4 to 9 procedures per month; and 9.4% of 10 or more monthly procedures. Conclusion: in the present study it was possible to identify that the majority of specialists in Orofacial Harmonization use the informed consent form, however, some of them still neglect its use(AU)

Effectiveness of topical hyaluronic acid of different molecular weights in xerosis cutis treatment in elderly: a double-blind, randomized controlled trial.

Dry skin is a common dermatological condition that frequently affects the elderly. A contributing cause to dry skin is a reduced concentration of hyaluronic acid (HA) in both the epidermis and dermis. The effectiveness of moisturizer containing HA as a therapy for dry skin is impacted by its specific molecular weight. Low molecular weight HA (LMWHA) is believed to be more effective in replenishing skin hydration in aging skin compared to High Molecular Weight HA (HMWHA) due to its ability to penetrate the stratum corneum. However, there is a lack of clinical research supporting this claim. A double-blind, randomized controlled trial was conducted on 36 residents of a nursing home in Jakarta. The participants, aged between 60 and 80 years, had been diagnosed with dry skin. Each test subject was administered three distinct, randomized moisturizing lotions (LMWHA, HMWHA, or vehicle), to be topically applied to three separate sites on the leg. Skin capacitance (SCap), transepidermal water loss (TEWL), and specified symptom sum score (SRRC) were measured at weeks 0, 2, and 4. After four weeks of therapy, area that was treated with LMWHA showed greater SCap values compared to the area treated with HMWHA (56.37 AU vs. 52.37 AU, p = 0.004) and vehicle (56.37 AU vs. 49.01 AU, p < 0.001). All groups did not show any significant differences in TEWL and SRRC scores. No side effects were found in all groups. The application of a moisturizer containing LMWHA to the dry skin of elderly resulted in significant improvements in skin hydration compared to moisturizers containing HMWHA and vehicle. Furthermore, these moisturizers demonstrated similar safety in treating dry skin in the elderly. ClinicalTrials.gov Identifier NCT06178367, https://clinicaltrials.gov/study/NCT06178367 .

A quality by design approach to optimise disulfide-linked hyaluronic acid hydrogels.

In this study, the disulfide-linked hyaluronic acid (HA) hydrogels were optimised for potential application as a scaffold in tissue engineering through the Quality by Design (QbD) approach. For this purpose, HA was first modified by incorporating the cysteine moiety into the HA backbone, which promoted the formation of disulfide cross-linked HA hydrogel at physiological pH. Utilising a Design of Experiments (DoE) methodology, the critical factors to achieve stable biomaterials, i.e. the degree of HA substitution, HA molecular weight, and coupling agent ratio, were explored. To establish a design space, the DoE was performed with 65 kDa, 138 kDa and 200 kDa HA and variable concentrations of coupling agent to optimise conditions to obtain HA hydrogel with improved rheological properties. Thus, HA hydrogel with a 12 % degree of modification, storage modulus of ≈2321 Pa and loss modulus of ≈15 Pa, was achieved with the optimum ratio of coupling agent. Furthermore, biocompatibility assessments in C28/I2 chondrocyte cells demonstrated the non-toxic nature of the hydrogel, underscoring its potential for tissue regeneration. Our findings highlight the efficacy of the QbD approach in designing HA hydrogels with tailored properties for biomedical applications.

Stretchable hydrogels of chitosan/hyaluronic acid induced by polyelectrolyte complexation around neutral pH.

In this work, we propose the formation of stretchable hydrogels at neutral pH from the physical crosslinking of chitosan (CS) and hyaluronic acid (HA) by polyelectrolyte complexation. A mixture of CS (Mw ≈ 600 kg/mol, degree of acetylation ≈ 50 %) solution and HA (Mw ≈ 77 kg/mol) solution was prepared with an excess of salts screening the electrostatic interactions CS/HA. In a controlled manner, the polyelectrolyte complexation was induced through the progressive dialysis of the salted polymer mixture against a sodium acetate solution (AcONa, 0.01 M) for 7 days. Depending on [HA], various materials were obtained: viscous solutions at [HA] = 0.75 % (w/v); hydrogels at [HA] = 1.50-2.24 % (w/v) with Young modulus of 14 kPa and stretchable to 200 %. The small angle X-ray scattering characterization of the hydrogels revealed a multiscale organization related to the conformation of the polymers induced by the physical interactions. The dialysis process with AcONa was optimized by adding a dialysis step against a zinc acetate solution containing Zn2+. The combination of polyelectrolyte complexation between CS/HA and metal complexation between Zn2+ and the polymers led to an enhancement of the hydrogel stretchability up to 400 %.

Biofunctionalized hydrogel composed of genipin-crosslinked gelatin/hyaluronic acid incorporated with lyophilized platelet-rich fibrin for segmental bone defect repair.

Segmental bone defects can arise from trauma, infection, metabolic bone disorders, or tumor removal. Hydrogels have gained attention in the field of bone regeneration due to their unique hydrophilic properties and the ability to customize their physical and chemical characteristics to serve as scaffolds and carriers for growth factors. However, the limited mechanical strength of hydrogels and the rapid release of active substances have hindered their clinical utility and therapeutic effectiveness. With ongoing advancements in material science, the development of injectable and biofunctionalized hydrogels holds great promise for addressing the challenges associated with segmental bone defects. In this study, we incorporated lyophilized platelet-rich fibrin (LPRF), which contains a multitude of growth factors, into a genipin-crosslinked gelatin/hyaluronic acid (GLT/HA-0.5 % GP) hydrogel to create an injectable and biofunctionalized composite material. Our findings demonstrate that this biofunctionalized hydrogel possesses optimal attributes for bone tissue engineering. Furthermore, results obtained from rabbit model with segmental tibial bone defects, indicate that the treatment with this biofunctionalized hydrogel resulted in increased new bone formation, as confirmed by imaging and histological analysis. From a translational perspective, this biofunctionalized hydrogel provides innovative and bioinspired capabilities that have the potential to enhance bone repair and regeneration in future clinical applications.

Hyaluronic acid-poly(glyceryl)10-stearate nanoemulsion for co-delivery of fish oil and resveratrol: Enhancing bioaccessibility and antioxidant potency.

Hyaluronic acid (HA), an endogenous polysaccharide comprising alternating D-glucuronic acid and N-acetylglucosamine units, is renowned for its high hydrophilicity, biocompatibility, and biodegradability. These attributes have rendered HA invaluable across medical and drug delivery fields. HA can be altered through physical, chemical, or enzymatic methods to improve the properties of the modified substances. In this work, we synthesized a derivative via the esterification of HA with poly(glyceryl)10-stearate (PG10-C18), designated as HA-PG10-C18. This novel derivative was employed to fabricate a nano co-delivery system (HA-PG10-C18@Res-NE) for fish oil and resveratrol (Res), aiming to enhance their stability and bioaccessibility. An exhaustive investigation of HA-PG10-C18@Res-NE revealed that the HA-modified system displayed superior physicochemical stability, notably in withstanding oxidation and neutralizing free radicals. Moreover, in vitro simulated digestion underscored the system's enhanced bioaccessibility of Res and more efficient release of free fatty acids. These outcomes underscore the strategic advantage of HA in modifying PG10-C18 for nanoemulsion formulation. Consequently, HA-PG10-C18 stands as a promising emulsifier for encapsulating lipophilic bioactives in functional foods, nutraceuticals, and pharmaceuticals.

Mild preparation of hyaluronic acid/silk fibroin sponges by modified crosslinking method.

The composites composed of hyaluronic acid (HA) and silk fibroin (SF) exhibit great potential in diverse biomedical applications. However, the utilization of commercial crosslinkers such as 1,4-butanediol diglycidyl ether (BDDE) for crosslinking HA typically necessitates harsh conditions involving strong alkaline, which greatly limits its potential applications. In this study, a mild modified approach was developed to fabricate HA/SF blend sponges crosslinked by BDDE without alkaline conditions. The blend solutions were cryo-concentrated to induce crosslinking reactions. The mechanism of freezing crosslinking was elucidated by investigating the effects of ice crystal growth and HA molecular weight on the degree of crosslinking. The results revealed that HA achieved efficient crosslinking when its molecular weight exceeds 1000 kDa and freezing temperatures ranged from -40 °C to -20 °C. After introducing SF, multiple crosslinks were formed between SF and HA chains, producing water-stable porous sponges. The SEM results demonstrated that the introduction of SF effectively enhanced the interconnectivity between macropores through creating subordinate holes onto the pores wall. Raising the SF content significantly enhanced compression strength, resistance to enzymatic degradation and cell viability of blend sponges. This study provides a novel strategy for designing bioactive HA/SF blend sponges as substitutes for tissue repair and wound dressing.

Function and contribution of two putative Enterococcus faecalis glycosaminoglycan degrading enzymes to bacteremia and catheter-associated urinary tract infection.

Enterococcus faecalis is a common cause of healthcare-acquired bloodstream infections and catheter-associated urinary tract infections (CAUTIs) in both adults and children. Treatment of E. faecalis infection is frequently complicated by multi-drug resistance. Based on protein homology, E. faecalis encodes two putative hyaluronidases, EF3023 (HylA) and EF0818 (HylB). In other Gram-positive pathogens, hyaluronidases have been shown to contribute to tissue damage and immune evasion, but the function in E. faecalis has yet to be explored. Here, we show that both hylA and hylB contribute to E. faecalis pathogenesis. In a CAUTI model, ΔhylA exhibited defects in bladder colonization and dissemination to the bloodstream, and ΔhylB exhibited a defect in kidney colonization. Furthermore, a ΔhylAΔhylB double mutant exhibited a severe colonization defect in a model of bacteremia while the single mutants colonized to a similar level as the wild-type strain, suggesting potential functional redundancy within the bloodstream. We next examined enzymatic activity, and demonstrate that HylB is capable of digesting both hyaluronic acid (HA) and chondroitin sulfate in vitro, while HylA exhibits only a very modest activity against heparin. Importantly, HA degradation by HylB provided a modest increase in cell density during the stationary phase and also contributed to dampening of lipopolysaccharide-mediated NF-κB activation. Overall, these data demonstrate that glycosaminoglycan degradation is important for E. faecalis pathogenesis in the urinary tract and during bloodstream infection.

Effect of catheter needle caliber on polidocanol foam stability in foam sclerotherapy.

Background: Although sclerotherapy is widely used to treat vascular malformations (VMs), it is associated with several challenges. One significant issue is the insufficient understanding of the influence of various factors on the stability of polidocanol (POL) foam used in sclerotherapy. Objective: This study aimed to explore the effect of the catheter needle caliber on foam stability when using POL with or without hyaluronic acid (HA) for the treatment of VMs. Methods and materials: The Tessari method generated sclerosant foam using POL both with and without HA. We used catheters and syringe needles of various calibers, and the resulting foam was transferred into new syringes to facilitate a comparison of foam stability. Foam half-life (FHT) was utilized as a metric to assess foam stability. Results: The study found that narrower needle calibers produced a more stable foam when POL was used alone; however, no significant effect was observed when HA was added. Furthermore, when the foam was expelled using catheters and syringe needles of the same size, no noticeable changes in the stability were observed. Conclusion: When choosing needles of varying calibers, their effect on foam stability should be carefully considered, particularly when the foam contains HA.

Fabrication and characteristics of multifunctional hydrogel dressings using dopamine modified hyaluronic acid and phenylboronic acid modified chitosan.

The healing of damaged skin is a complex and dynamic process, and the multi-functional hydrogel dressings could promote skin tissue healing. This study, therefore, explored the development of a composite multifunctional hydrogel (HDCP) by incorporating the dopamine modified hyaluronic acid (HA-DA) and phenylboronic acid modified chitosan (CS-PBA) crosslinked using boric acid ester bonds. The integration of HA-DA and CS-PBA could be confirmed using the Fourier transform infrared spectrometer and 1H nuclear magnetic resonance analyses. The fabricated HDCP hydrogels exhibited porous structure, elastic solid behavior, shear-thinning, and adhesion properties. Furthermore, the HDCP hydrogels exhibited antibacterial efficacy against Gram-negative Escherichia coli (E. coli) and Gram-positive Staphylococcus aureus (S. aureus). Subsequently, the cytocompatibility of the HDCP hydrogels was verified through CCK-8 assay and fluorescent image analysis following co-cultivation with NIH-3T3 cells. This research presents an innovative multifunctional hydrogel that holds promise as a wound dressing for various applications within the realm of wound healing.

Hyaluronic Acid-Bilirubin Nanoparticles as a Tumor Microenvironment Reactive Oxygen Species-Responsive Nanomedicine for Targeted Cancer Therapy.

Introduction: The tumor microenvironment (TME) has attracted considerable attention as a potential therapeutic target for cancer. High levels of reactive oxygen species (ROS) in the TME may act as a stimulus for drug release. In this study, we have developed ROS-responsive hyaluronic acid-bilirubin nanoparticles (HABN) loaded with doxorubicin (DOX@HABN) for the specific delivery and release of DOX in tumor tissue. The hyaluronic acid shell of the nanoparticles acts as an active targeting ligand that can specifically bind to CD44-overexpressing tumors. The bilirubin core has intrinsic anti-cancer activity and ROS-responsive solubility change properties. Methods & Results: DOX@HABN showed the HA shell-mediated targeting ability, ROS-responsive disruption leading to ROS-mediated drug release, and synergistic anti-cancer activity against ROS-overproducing CD44-overexpressing HeLa cells. Additionally, intravenously administered HABN-Cy5.5 showed remarkable tumor-targeting ability in HeLa tumor-bearing mice with limited distribution in major organs. Finally, intravenous injection of DOX@HABN into HeLa tumor-bearing mice showed synergistic anti-tumor efficacy without noticeable side effects. Conclusion: These findings suggest that DOX@HABN has significant potential as a cancer-targeting and TME ROS-responsive nanomedicine for targeted cancer treatment.

Early periodontal wound healing after chlorhexidine rinsing: a randomized clinical trial.

OBJECTIVES: This single-center randomized, parallel design, clinical trial with a 2-week follow-up involved patients affected by periodontitis undergoing periodontal surgery. The aim was to evaluate periodontal surgical wound healing with the use of chlorhexidine-based mouth rinses versus an untreated control group. MATERIALS AND METHODS: Periodontal surgery was performed following a standardized protocol. Patients were randomly prescribed i) chlorhexidine (CHX) + anti-discoloration system (ADS) + hyaluronic acid (HA), ii) CHX + ADS or iii) no treatment (control group). Plaque score, gingival inflammation, and Early Healing Index (EHI), assessing the degree of wound closure and the presence of fibrin and necrosis, were evaluated at 3, 7 and 14 days after surgery. RESULTS: In total, 33 patients were enrolled. Patients were comparable at baseline for all measured clinical parameters. At 3-days wound healing was significantly improved in all patients treated with CHX + ADS-based mouth rinses with a lower EHI score at the interdental papillae compared with control group (p < 0.01). CHX + ADS + HA group presented improved healing across all time points in terms of EHI, plaque containment, and gingival inflammation when compared to control group (p < 0.01). CONCLUSIONS: The usage of CHX-ADS following periodontal surgery improved early wound healing, reduced plaque accumulation and gingival inflammation. During the early post-operative period the adjunct of HA further improved soft tissue closure. CLINICAL RELEVANCE: This study aims at evaluating the response of gingival tissues to mouth rinsing with chlorhexidine and anti-discoloration system (CHX + ADS) or CHX + ADS + hyaluronic acid (CHX + ADS + HA) versus no rinse in terms of healing of the periodontal surgical wound. CHX + ADS mouth rinses enhanced early soft tissue closure after periodontal surgery and contributed to the reduction in plaque accumulation and gingival inflammation. The adjunct of HA may be beneficial especially in the early post-operative period. CHX + ADS administration following periodontal surgery may improve soft tissue healing in the first two post-operative weeks.

Teaching an Old Drug a New Trick: Targeting Treatment Resistance in Genitourinary Cancers.

In the quest for improving the clinical outcome of patients with metastatic genitourinary cancers, including metastatic renal cell carcinoma (mRCC), the emphasis often is on finding new targeted therapies. However, two studies by Jordan et al. (Oncogenesis 2020) and Wang et al. (Cancer Cell Int 2022) demonstrate the feasibility of improving the efficacy of a modestly effective drug Sorafenib against mRCC by attacking a mechanism hijacked by RCC cells for inactivating Sorafenib. The studies also identified hyaluronic acid synthase -3 (HAS3) as a bonafide target of Sorafenib in RCC cells. The studies demonstrate that an over-the-counter drug Hymecromone (4-methylumbelliferone) blocks inactivation of Sorafenib in RCC cells and improves its efficacy against mRCC through the inhibition of HAS3 expression and HA signaling. In the broader context, improving the efficacy of "old and failed drugs" that have favorable safety profiles should increase the availability of effective treatments for patients with advanced cancers.

A hyaluronic acid hydrogel as a mild photothermal antibacterial, antioxidant, and nitric oxide release platform for diabetic wound healing.

Hyaluronic acid (HA)-based biopolymer hydrogels are promising therapeutic dressings for various wounds but still underperform in treating diabetic wounds. These wounds are extremely difficult to heal and undergo a prolonged and severe inflammatory process due to bacterial infection, overexpression of reactive oxygen species (ROS), and insufficient synthesis of NO. In this study, a dynamic crosslinked hyaluronic acid (HA) hydrogel dressing (Gel-HAB) loaded with allomelanin (AMNP)-N, N'-dis-sec-butyl-N, N'-dinitroso-1, 4-phenylenediamine (BNN6) nanoparticles (AMNP-BNN6) was developed for healing diabetic wounds. The dynamic acylhydrazone bond formed between hydrazide-modified HA (HA-ADH) and oxidized HA (OHA) makes the hydrogel injectable, self-healing, and biocompatible. The hydrogel, loaded with AMNP-BNN6 nanoparticles, exhibits promising ROS scavenging ability and on-demand release of nitric oxide (NO) under near-infrared (NIR) laser irradiation to achieve mild photothermal antibacterial therapy (PTAT) (∼ 48 °C). Notably, the Gel-HAB hydrogel effectively reduced the oxidative stress level, controlled infections, accelerated vascular regeneration, and promoted angiogenesis, thereby achieving rapid healing of diabetic wounds. The injectable self-healing nanocomposite hydrogel could serve as a mild photothermal-enhanced antibacterial, antioxidant, and nitric oxide release platform for the treatment of diabetic wounds.

Hyaluronic acid-coated liposomes for enhanced in vivo efficacy of neogambogic acid via active tumor cell targeting and prolonged systemic exposure.

Neogambogic acid (NGA), which possesses a variety of anticancer activities, is visualized as an anticancer bioactive ingredient. However, the huge vascular stimulation, poor aqueous solubility, and short half-life restricted its clinical use. In this work, an effective nanocarrier was explored to reduce toxicity and enhance the tumor-targeted delivery. Two liposomal formulations, neogambogic acid liposomes (NGA-L), and hyaluronic acid-coated neogambogic acid liposomes (HA-NGA-L) were prepared and characterized with high encapsulation efficiency, slow pattern of drug release, narrow size distribution and higher stability. The cytotoxicity and cellular uptake of HA-NGA-L were higher than those of NGA-L in MDA-MB-231 cells (high CD44 expression), while no obvious differences in MCF-7 cells with (low CD44 expression), suggesting the CD44-mediated cellular internalization of hyaluronic acid-modified liposomes enhanced the cytotoxicity. Mechanistically, elevation of Bax and caspase-3 as well as downregulation of Bcl-2 led to cell apoptosis. Besides, the vascular stimulation and the hemolysis test indicated good safety of HA-NGA-L. In addition, HA-NGA-L was the effective nanocarrier to repress tumor proliferation in MDA-MB-231 tumor xenograft mouse through CD44 mediated active targeting without any obvious histopathological abnormities on major organs. Immunohistochemistry analysis revealed the enhanced elevation of Bax and caspase-3, and reduced expression of Bcl-2 contribute to apoptosis in tumors. Meanwhile, HA-NGA-L increased the AUC and t1/2 by 5.34-fold and 3.94-fold, respectively. In summary, the present study shows that HA-NGA-L may be safe and effective for the tumor-targeted delivery of neogambogic acid.

Evaluation of the restorative effect of ozone and chitosan-hyaluronic acid with and without mesenchymal stem cells on wound healing in rats.

This study evaluated the effect of ozone, chitosan-hyaluronic (Cs-HA) acid and mesenchymal stem cells (MSCs) on wound healing in rats. A total of 64 rats were randomly divided into four groups: control, ozone, Cs-HA + ozone and Cs-HA + ozone + MSCs. A 5 mm full-thickness wound was created on the back of each rat. The wound area was measured macroscopically on days 3, 5, 9 and 14. Tissue sections were prepared for histopathological evaluation of inflammation, collagen arrangement, neovascularization and epithelial tissue rearrangement. Macroscopic assessment showed differences in wound area on days 5, 9 and 14. Histopathological examination showed that the Cs-HA + ozone + MSCs and Cs-HA + ozone groups had significantly higher vascularization on day 3 compared to the ozone-treated and control groups. All treatment groups had significantly better collagen arrangement than the control group. On day 5, no significant difference was observed between different groups. On day 9, the inflammation level in the Cs-HA + ozone + MSCs group was significantly lower than in the other groups. All treatment groups had significantly better vascularization compared to the control group. On day 14, the rate of inflammation was significantly lower in the treatment groups than in the control group. Significantly higher collagen arrangement levels were observed in the Cs-HA + ozone and Cs-HA + ozone + MSCs groups compared to the control and ozone groups. All treatment groups had significantly better epithelial tissue rearrangement than the control group. Overall, the results of this study indicated that treatment with ozone, Cs-HA acid, Cs-HA and MSCs accelerated wound healing in rats. The effect of using Cs-HA acid with mesenchymal cells was better than the other types of treatment. Larger clinical trials are needed to assess these factors for improving chronic wound treatment.

Efficacy of Superselective Intra-arterial Recanalization of Embolized Arteries Resulting from Facial Hyaluronic Acid Injection.

BACKGROUND: Arterial embolism is a rare complication caused by hyaluronic acid (HA) injection. However, it is one of the most serious complications. Once it happens, the complication would have a great and long-term impact on patients. Intra-arterial recanalization has been reported for recovering the visual acuity in patients with visual loss caused by hyaluronic acid. There is little report about the benefits of superselective intra-arterial recanalization therapy for skin wounds caused by hyaluronic acid vascular embolization. METHODS: Eight patients who had received the superselective intra-arterial recanalization therapy were retrospectively reviewed. Hyaluronidase was injected into the facial artery by superselective intra-arterial recanalization therapy, followed by symptomatic treatment. The facial artery recanalization was successfully performed and no interventional procedure-related adverse events happened. RESULTS: Arterial embolization accompanies by the interruption or reduction of blood supply, followed by ochrodermia, pain, numbness, swelling, yellowish white secreta and even necrosis on skin wound area. Early detection of skin blood supply disorders and early recovery of blood supply are very critical to treat facial artery embolization caused by HA. After superselective intra-arterial recanalization therapy, the blood supply to facial skin was restored and skin wounds recovered in all patients. Only 1 patient was left with small and superficial scars. CONCLUSION: Superselective intra-arterial recanalization therapy is an effective and safe method that can alleviate skin wounds caused by HA vascular embolization. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

All-trans retinoic acid pretreatment of mesenchymal stem cells enhances the therapeutic effect on acute kidney injury.

A promising new therapy option for acute kidney injury (AKI) is mesenchymal stem cells (MSCs). However, there are several limitations to the use of MSCs, such as low rates of survival, limited homing capacity, and unclear differentiation. In search of better therapeutic strategies, we explored all-trans retinoic acid (ATRA) pretreatment of MSCs to observe whether it could improve the therapeutic efficacy of AKI. We established a renal ischemia/reperfusion injury model and treated mice with ATRA-pretreated MSCs via tail vein injection. We found that AKI mice treated with ATRA-MSCs significantly improved renal function compared with DMSO-MSCs treatment. RNA sequencing screened that hyaluronic acid (HA) production from MSCs promoted by ATRA. Further validation by chromatin immunoprecipitation experiments verified that retinoic acid receptor RARα/RXRγ was a potential transcription factor for hyaluronic acid synthase 2. Additionally, an in vitro hypoxia/reoxygenation model was established using human proximal tubular epithelial cells (HK-2). After co-culturing HK-2 cells with ATRA-pretreated MSCs, we observed that HA binds to cluster determinant 44 (CD44) and activates the PI3K/AKT pathway, which enhances the anti-inflammatory, anti-apoptotic, and proliferative repair effects of MSCs in AKI. Inhibition of the HA/CD44 axis effectively reverses the renal repair effect of ATRA-pretreated MSCs. Taken together, our study suggests that ATRA pretreatment promotes HA production by MSCs and activates the PI3K/AKT pathway in renal tubular epithelial cells, thereby enhancing the efficacy of MSCs against AKI.

Collagen-Mesenchymal Stem Cell Microspheres Embedded in Hyaluronic Acid Solutions as Biphasic Stem Niche Delivery Systems for Pulmonary Differentiation.

Cell therapy has the potential to become a feasible solution for several diseases, such as those related to the lungs and airways, considering the more beneficial intratracheal administration route. However, in lung diseases, an impaired pulmonary extracellular matrix (ECM) precludes injury resolution with a faulty engraftment of mesenchymal stem cells (MSCs) at the lung level. Furthermore, a shielding strategy to avoid cell damage as well as cell loss due to backflow through the injection path is required. Here, an approach to deliver cells encapsulated in a biomimetic stem niche is used, in which the interplay between cells and physiological lung ECM constituents, such as collagen and hyaluronic acid (HA), can occur. To this aim, a biphasic delivery system based on MSCs encapsulated in collagen microspheres (mCOLLs) without chemical modification and embedded in an injectable HA solution has been developed. Such biphasic delivery systems can both increase the mucoadhesive properties at the site of interest and improve cell viability and pulmonary differentiation. Rheological results showed a similar viscosity at high shear rates compared to the MSC suspension used in intratracheal administration. The size of the mCOLLs can be controlled, resulting in a lower value of 200 µm, suitable for delivery in alveolar sacs. Biological results showed that mCOLLs maintained good cell viability, and when they were suspended in lung medium implemented with low molecular weight HA, the differentiation ability of the MSCs was further enhanced compared to their differentiation ability in only lung medium. Overall, the results showed that this strategy has the potential to improve the delivery and viability of MSCs, along with their differentiation ability, in the pulmonary lineage.

Immature mandarin orange extract increases the amount of hyaluronic acid in human skin fibroblast and keratinocytes.

Immature mandarin orange is thinned in order to maturation of orange. To use immature mandarin orange as a cosmetic functional material, we investigated the seasonal fluctuation changes in hesperidin and narirutin levels of immature mandarin oranges, and the effects on human skin cells. The contents of hesperidin from Aoshima, Otsu, and Shonan gold, is higher at about a month after flowering. Shonan gold has higher content of narirutin to compere that of Aoshima and Otsu. We found the addition of immature mandarin orange extracts to the human skin fibroblasts and keratinocytes, gene expression level of hyaluronic acid synthase and the hyaluronic acid contents in the medium are higher than that of the control. It was suggested that hesperidin in immature mandarin orange enhances the ability of skin cells to produce hyaluronic acid. Our findings indicate that the immature mandarin orange is a characteristic material on cosmetics and functional foods.