Recent Progress in Innate Immune Responses to Enterovirus A71 and Viral Evasion Strategies.

Enterovirus A71 (EV-A71) is a major pathogen causing hand, foot, and mouth disease (HFMD) in children worldwide. It can lead to severe gastrointestinal, pulmonary, and neurological complications. The innate immune system, which rapidly detects pathogens via pathogen-associated molecular patterns or pathogen-encoded effectors, serves as the first defensive line against EV-A71 infection. Concurrently, the virus has developed various sophisticated strategies to evade host antiviral responses and establish productive infection. Thus, the virus-host interactions and conflicts, as well as the ability to govern biological events at this first line of defense, contribute significantly to the pathogenesis and outcomes of EV-A71 infection. In this review, we update recent progress on host innate immune responses to EV-A71 infection. In addition, we discuss the underlying strategies employed by EV-A71 to escape host innate immune responses. A better understanding of the interplay between EV-A71 and host innate immunity may unravel potential antiviral targets, as well as strategies that can improve patient outcomes.

Changes of Temporomandibular Joint Morphology and Symptoms in Class II Malocclusion Patients With Bilateral Sagittal Split Ramous Osteotomy.

This study included 46 patients with class II malocclusion ranging in age from 19 to 39 years old treated with bilateral sagittal split ramous osteotomy (BSSRO). Left and right temporomandibular joints (TMJs) of each subject were evaluated independently with cone-beam computed tomography (CBCT) before operation (T1), 1 week after operation (T2), and 1 year after operation (T3) and assessed the effects of orthognathic surgery (OGS) on the temporomandibular joint disease (TMD) symptoms. Temporomandibular joint morphology evaluation included condylar volume, condylar area, cortical bone thickness, depth of the mandibular fossa, fossa thickness, joint nodule angle, joint space, and condyle-fossa relationship, which were calculated by using the Mimics software and 3-matic software. Data were statistically analyzed with SPSS software (P <0.05 means statistically significant). In our study, bilateral TMJs have no difference in T3. Bilateral sagittal split ramous osteotomy had no significant effect on the articular fossa. The condyle volume and surface area decreased from T1 to T3, but the cortical thickness of the bone did not change significantly. More anterior condyle positions in T1 and more posterior in T3.21 patients had at least 1 sign or symptom of TMD in T1 and 27 patients in T3. Four patients who were asymptomatic in T1 developed pain after surgery, 10 developed noises, 12 showed limited mouth opening, and 8 had abnormal opening patterns. It is concluded that more condylar posterior position after BSSRO and the reduction of condyle may be related to the enlargement of anterior space. The number of patients with joint symptoms increased postoperative, and the impact of BSSRO on TMD may be negative.

Effect of polyhydroxy-terminated PAMAM dendrimer on dentin matrix metalloproteinases within the hybrid layers.

BACKGROUND: Intrafibrillar remineralization within the hybrid layers (HLs) has recently attracted extensive attention in achieving durable resin-dentin bonds. The polyhydroxy-terminated poly(amidoamine) dendrimer (PAMAM-OH) at fourth generation becomes a desirable candidate to induce intrafibrillar remineralization to protect exposed collagen fibrils within HLs based on the size exclusion effect of fibrillar collagen. However, the remineralization process in vivo is time-consuming, during which the exposed collagen fibrils are vulnerable to enzymatic degradation, resulting in unsatisfactory remineralization. Thereby, if PAMAM-OH itself possesses concomitant anti-proteolytic activity during the induction of remineralization, it would be very beneficial to obtain satisfactory remineralization. METHODS: Binding capacity tests using adsorption isotherm and confocal laser scanning microscopy (CLSM) were performed to assess if the PAMAM-OH had adsorption capacity on dentin. Anti-proteolytic testings were detected by MMPs assay kit, in-situ zymography and ICTP assay. Adhesive infiltration of resin-dentin interface and tensile bond strength before and after thermomechanical cycling were implemented to assess if the PAMAM-OH adversely affected resin-dentin bonds. RESULTS: Anti-proteolytic testings performed using MMPs assay kit, in-situ zymography and ICTP assay indicated that PAMAM-OH inhibited exogenous soluble MMP-9 as well as had inhibitory effect on the endogenous proteases. Adhesive infiltration of resin-dentin interface and tensile bond strength before and after thermomechanical cycling were implemented to indicate that the PAMAM-OH pretreatment had no adverse effects on immediate dentin bonding and prolonged the durability of resin-dentin bonds. CONCLUSIONS: PAMAM-OH possesses anti-proteolytic activity and prevents exposed collagen fibrils within HLs from degradation, which lays the foundation for the satisfactory intrafibrillar remineralization induced by PAMAM-OH within HLs to achieve durable resin-dentin bonds in the next work.

A Dendritic Cells-Targeting Nano-Vaccine by Coupling Polylactic-Co-Glycolic Acid-Encapsulated Allergen with Mannan Induces Regulatory T Cells.

BACKGROUND: The efficacy of allergen-specific immunotherapy (AIT) is mainly depended on the tolerogenic immune responses elicited. Properly conjugated nano-vaccine has the advantages of both specific targeting and continuous and on-demand release of allergen. OBJECTIVES: The aim of this study is to investigate the effects of a dendritic cells (DCs)-targeting nano-vaccine for AIT. METHODS: The nano-vaccine was produced by coupling polylactic-co-glycolic acid (PLGA)-encapsulated ovalbumin (OVA) with mannan. Allergen capture, human monocytes-derived DCs (hMoDCs) activation, and T cells responses were assessed by flow cytometry, confocal microscopy, quantitative real-time PCR, ELISA, and Cytometric Bead Array. Balb/c mice were immunized with the nano-vaccines, and the immune responses were analyzed. RESULTS: OVA-PLGA nanoparticle (NP) displayed favorable safety profile. OVA-mannan-PLGA NP was captured more efficiently by hMoDCs than OVA-PLGA NP, which was mediated mainly through DC-specific intercellular adhesion molecule 3-grabbing nonintegrin. A tolerogenic phenotype of hMoDCs was induced by OVA-mannan-PLGA NP, but not OVA-PLGA NP, and increased number of regulatory T (Treg) cells was generated subsequently in in vitro coculture. Immunization of Balb/c mice with OVA-mannan-PLGA NP resulted in lower serum level of OVA-specific immunoglobulins and less production of pro-inflammatory cytokines in splenocytes culture than the mice immunized with OVA-PLAG NP, PLGA NP, or OVA, while the number of splenic Treg cells was higher in OVA-mannan-PLGA group than in other groups. Moreover, preimmunization with OVA-mannan-PLGA NP significantly inhibited the Th2 immune response induced by OVA sensitization. CONCLUSIONS: The biocompatible PLGA-encapsulated OVA coupling with mannan has augmented ability for tolerance induction and could be developed as a novel vaccine for AIT.

Microfluidic formation of highly monodispersed multiple cored droplets using needle-based system in parallel mode.

Scale-up in droplet microfluidics achieved by increasing the number of devices running in parallel or increasing the droplet makers in the same device can compromise the narrow droplet-size distribution, or requires high fabrication cost, when glass- or polymer-based microdevices are used. This paper reports a novel way using parallelization of needle-based microfluidic systems to form highly monodispersed droplets with enhanced production rates yet in cost-effective way, even when forming higher order emulsions with complex inner structure. Parallelization of multiple needle-based devices could be realized by applying commercially available two-way connecters and 3D-printed four-way connectors. The production rates of droplets could be enhanced around fourfold (over 660 droplets/min) to eightfold (over 1300 droplets/min) by two-way connecters and four-way connectors, respectively, for the production of the same kind of droplets than a single droplet maker (160 droplets/min). Additionally, parallelization of four-needle sets with each needle specification ranging from 34G to 20G allows for simultaneous generation of four groups of PDMS microdroplets with each group having distinct size yet high monodispersity (CV < 3%). Up to six cores can be encapsulated in double emulsion using two parallelly connected devices via tuning the capillary number of middle phase in a range of 1.31 × 10-4 to 4.64 × 10-4 . This study leads to enhanced production yields of droplets and enables the formation of groups of droplets simultaneously to meet extensive needs of biomedical and environmental applications, such as microcapsules with variable dosages for drug delivery or drug screening, or microcapsules with wide range of absorbent loadings for water treatment.

[The Role of HMGN2 in the Development of Periodontitis Dental Plaque].

OBJECTIVES: To determine the role of high mobility group chromosomal protein N2 (HMGN2) in the development of periodontitis plaque biofilm. METHODS: Saliva samples were collected before clinical interventions in patients with periodontitis (25 Mild periodontitis, 25 Moderate periodontitis and 25 Severe periodontitis) and healthy controls ( n=25).Following an estimation of dental plaque index, the level of HMGN2 in saliva was determined by enzyme-linked immunosorbent assay (ELISA).The recombinant human HMGN2 protein was purified and tested, its inhibitive effects on Porphyromonas gingivalis (P.g)growth and formation of P.g bioflim were detected by K-B antibacterial annulus and crystal violet staining, respectively. RESULTS: The healthy controls had lower levels of HMGN2 in saliva than those with periodontitis, especially those with severe periodontitis ( P<0.01).The level of HMGN2 was negatively correlated with dental plaque index ( r=-0.363, P<0.05). HMGN2 inhibited the development of main periodontal bacteria biofilm ( P<0.05). CONCLUSIONS: HMGN2 is involved in the development of periodontitis plaque biofilm and plays an important role in the development of periodontitis.

Cation-crosslinkedκ-carrageenan sub-microgel medium for high-quality embedded bioprinting.

Three-dimensional (3D) bioprinting embedded within a microgel bath has emerged as a promising strategy for creating intricate biomimetic scaffolds. However, it remains a great challenge to construct tissue-scale structures with high resolution by using embedded 3D bioprinting due to the large particle size and polydispersity of the microgel medium, as well as its limited cytocompatibility. To address these issues, novel uniform sub-microgels of cell-friendly cationic-crosslinked kappa-carrageenan (κ-Car) are developed through an easy-to-operate mechanical grinding strategy. Theseκ-Car sub-microgels maintain a uniform submicron size of around 642 nm and display a rapid jamming-unjamming transition within 5 s, along with excellent shear-thinning and self-healing properties, which are critical for the high resolution and fidelity in the construction of tissue architecture via embedded 3D bioprinting. Utilizing this new sub-microgel medium, various intricate 3D tissue and organ structures, including the heart, lungs, trachea, branched vasculature, kidney, auricle, nose, and liver, are successfully fabricated with delicate fine structures and high shape fidelity. Moreover, the bone marrow mesenchymal stem cells encapsulated within the printed constructs exhibit remarkable viability exceeding 92.1% and robust growth. Thisκ-Car sub-microgel medium offers an innovative avenue for achieving high-quality embedded bioprinting, facilitating the fabrication of functional biological constructs with biomimetic structural organizations.

Precision detection of hepatocellular carcinoma-associated telomerase RNA with SA@Comb-HCR nanosystem.

Accurate intracellular visualization of human telomerase RNA (hTR) is imperative for early diagnosis and treatment monitoring of hepatocellular carcinoma (HCC). While isothermal amplification-based DNA cascade strategies are promising, challenges persist in achieving great intake efficiency of detection probes within tumor cells and enhancing intracellular reaction efficiency. This study introduces a SA@Comb-HCR nanosystem, a highly effective approach for in situ hTR detection in HCC cells. Sodium alginate-coated liposomes ensures efficient nanoprobe delivery, which are then combined with proximity effect-inspired signal amplification. The coating of sodium alginate facilitates receptor-mediated endocytosis, prevents serum protein adhesion, and mitigates cationic liposome cytotoxicity. The designed Comb-like consolidated hairpin probe enhances the concentration of the local reactant, resulting in cascade amplification upon hTR activation. This technique achieves precision detection of intracellularly overexpressed hTR in HCC cells with a remarkable detection limit of 0.7 pM. This approach holds great promise for advancing targeted and sensitive early clinical diagnosis of HCC.

Embedded Bioprinting of Tissue-like Structures Using κ-Carrageenan Sub-Microgel Medium.

Embedded three-dimensional (3D) bioprinting utilizing a granular hydrogel supporting bath has emerged as a critical technique for creating biomimetic scaffolds. However, engineering a suitable gel suspension medium that balances precise bioink deposition with cell viability and function presents multiple challenges, particularly in achieving the desired viscoelastic properties. Here, a novel κ-carrageenan gel supporting bath is fabricated through an easy-to-operate mechanical grinding process, producing homogeneous sub-microscale particles. These sub-microgels exhibit typical Bingham flow behavior with small yield stress and rapid shear-thinning properties, which facilitate the smooth deposition of bioinks. Moreover, the reversible gel-sol transition and self-healing capabilities of the κ-carrageenan microgel network ensure the structural integrity of printed constructs, enabling the creation of complex, multi-layered tissue structures with defined architectural features. Post-printing, the κ-carrageenan sub-microgels can be easily removed by a simple phosphate-buffered saline wash. Further bioprinting with cell-laden bioinks demonstrates that cells within the biomimetic constructs have a high viability of 92% and quickly extend pseudopodia, as well as maintain robust proliferation, indicating the potential of this bioprinting strategy for tissue and organ fabrication. In summary, this novel κ-carrageenan sub-microgel medium emerges as a promising avenue for embedded bioprinting of exceptional quality, bearing profound implications for the in vitro development of engineered tissues and organs.

Antigen-Capturing Dendritic-Cell-Targeting Nanoparticles for Enhanced Tumor Immunotherapy Based on Photothermal-Therapy-Induced In Situ Vaccination.

In situ vaccines have revolutionized immunotherapy as they can stimulate tumor-specific immune responses, with the cancer being the antigen source. However, the heterogeneity of tumor antigens and insufficient dendritic cells (DCs) activation result in low cancer immunogenicity and hence poor vaccine response. Herein, a new in situ vaccine composed of acid-responsive liposome-coated polydopamine (PDA) nanoparticles modified with mannose and loaded with resiquimod (R848) is designed to promote the efficacy of immunotherapy. The in situ vaccine can actively target the tumor site based on the decomposition of the liposome, while the PDA nanoparticles promote photothermal therapy and capture the immunogenic cell-death-induced tumor-associated antigens based on the adsorption effect of dopamine-mimetic mussels. The PDA nanoparticles, which are modified with a mannose ligand, target the DCs and release R848 for activated antigen presentation. As a result, the in situ vaccine not only effectively activates the maturation of the DCs but also significantly enhances their effect on cytotoxic T lymphocyte cells. Furthermore, the vaccine effectively inhibits the distant recurrence and metastasis of tumors via long-term immune memory effects. Therefore, the in situ vaccine provides a potential strategy for improving the efficacy of cancer immunotherapy.

Atropine-eluting silicone contact lenses for myopia control.

Myopia, also known as nearsightedness, is one of the prime reasons for vision impairment worldwide. Atropine in topical ophthalmic solutions (e.g., 0.01% atropine sulfate eye drops) is the primary medical treatment for controlling myopia, especially for pseudomyopia or true myopia in rapid progress. However, aqueous atropine solution is unstable and easily breaks down to tropic acid, which will result in vision blur. Drug-eluting contact lenses (CLs) have been explored as a potentially superior alternative to effectively control the drug release and improve the drug efficacy. In this work, an atropine-eluting contact lens was developed by encapsulating an atropine implant in a silicon-based contact lens, towards functioning in vision correction and controlling myopia. The safety and effectiveness of this atropine-eluting contact lens were verified with rabbit and guinea pig models. The results showed that the lenses reduced the side effects like mydriasis and no other adverse events were observed in rabbit eyes. More importantly, atropine-loaded lenses could effectively delay the progress of form-deprivation myopia with guinea pig eyes as the model. Thus, we concluded that atropine-eluting CLs prepared by implantation technology may be an option for the treatment of myopia.

Multifunctional Liposomes Remodeling Tumor Immune Microenvironment for Tumor Chemoimmunotherapy.

In the treatment of solid tumors, the complex barriers composed of cancer-associated fibroblasts (CAFs) prevent drug delivery and T cells infiltration into tumor tissues. Although nanocarriers hold great prospects in drug delivery, fibrosis causes the biological barrier and immunosuppressive tumor microenvironment (ITM) that impairs the anti-tumor efficacy of nanocarriers. Here, a small dendritic macromolecule loaded with doxorubicin (PAMAM-ss-DOX) (DP) is synthesized and encapsulated into pH-responsive nanoliposome, together with adjuvant toll-like receptor 7/8 (TLR7/8) agonist resiquimod (R848) and losartan (LOS). The pH-responsive liposome facilitates the simultaneous and effective delivery of DP, R848, and LOS, which can decompose and release these drugs under the acidic tumor microenvironment. The small sized DP (≈25 nm) with the ability to penetrate into tumor tissue and immunogenic cell death (ICD) can reverse the ITM and elicit immune response, which is equivalent to the effect of an in situ vaccine. Moreover, LOS reduces the activity of CAFs effectively, which can contribute to the infiltration of T cells. Therefore, this nano-platform provides a new therapeutic strategy for enhanced chemo-immunotherapy.

Repairing gastric ulcer with hyaluronic acid/extracellular matrix composite through promoting M2-type polarization of macrophages.

The treatment of gastric ulcer and perforation using synthetic and biomaterials has been a clinical challenge. In this work, a drug-carrying layer of hyaluronic acid was combined with a gastric submucosal decellularized extracellular matrix called gHECM. The regulation of macrophage polarization by the extracellular matrix's components was then investigated. This work proclaims how gHECM responds to inflammation and aids in the regeneration of the gastric lining by altering the phenotype of surrounding macrophages and stimulating the body's whole immune response. In a nutshell, gHECM promotes tissue regeneration by changing the phenotype of macrophages around the site of injury. In particular, gHECM reduces the production of pro-inflammatory cytokines, decreases the percentage of M1 macrophages, and further encourages differentiation of macrophage subpopulation to the M2 phenotype and the release of anti-inflammatory cytokines, which could block the NF-κB pathway. Activated macrophages are capable of immediately delivering through spatial barriers, modulating the peripheral immune system, influencing the inflammatory microenvironment, and ultimately promoting the recovery of inflammation and healing of ulcers. They contribute to the secreted cytokines that act on local tissues or enhance the chemotactic ability of macrophages through paracrine secretion. In this study, we focused on the immunological regulatory network of macrophage polarization to further develop the mechanisms behind this process. Nevertheless, the signaling pathways involved in this process need to be further explored and identified. We think that our research will encourage more investigation into how the decellularized matrix affects immune modulation and will help the decellularized matrix perform better as a new class of natural biomaterials for tissue engineering.

Copy-number mutations on chromosome 17q24.2-q24.3 in congenital generalized hypertrichosis terminalis with or without gingival hyperplasia.

Congenital generalized hypertrichosis terminalis (CGHT) is a rare condition characterized by universal excessive growth of pigmented terminal hairs and often accompanied with gingival hyperplasia. In the present study, we describe three Han Chinese families with autosomal-dominant CGHT and a sporadic case with extreme CGHT and gingival hyperplasia. We first did a genome-wide linkage scan in a large four-generation family. Our parametric multipoint linkage analysis revealed a genetic locus for CGHT on chromosome 17q24.2-q24.3. Further two-point linkage and haplotyping with microsatellite markers from the same chromosome region confirmed the genetic mapping and showed in all the families a microdeletion within the critical region that was present in all affected individuals but not in unaffected family members. We then carried out copy-number analysis with the Affymetrix Genome-Wide Human SNP Array 6.0 and detected genomic microdeletions of different sizes and with different breakpoints in the three families. We validated these microdeletions by real-time quantitative PCR and confirmed their perfect cosegregation with the disease phenotype in the three families. In the sporadic case, however, we found a de novo microduplication. Two-color interphase FISH analysis demonstrated that the duplication was inverted. These copy-number variations (CNVs) shared a common genomic region in which CNV is not reported in the public database and was not detected in our 434 unrelated Han Chinese normal controls. Thus, pathogenic copy-number mutations on 17q24.2-q24.3 are responsible for CGHT with or without gingival hyperplasia. Our work identifies CGHT as a genomic disorder.

Speciation and release risk of heavy metals bonded on simulated naturally-aged microplastics prepared from artificially broken macroplastics.

The negative impact of microplastics (MPs) act as metals vectors to environment and ecosystem have been paid more and more attention, and the accumulation risk of them to human body through the food chains and food webs needs to attract attention. In addition, the MPs bonded with heavy metals transport from river into the sea with high salinity may also have metals release risk. Herein, natural aged microplastics prepared from artificially broken macroplastics adsorbed with heavy metals accumulated from the natural environment were tested for their states and release risk in several simulated solution (NaCl and gastrointestinal solutions) to understand their effects on environment and human health. The adsorption capacity of different heavy metals on MPs was different during natural aging process proved by four-acid digestion method. Metals with high accumulation (including Pb, As, Cr, Mn, Ni, Zn, Co, Cu and Cd) on NAMPs were selected for further study. Results obtained via three-step extraction method showed that these heavy metals were mainly present as acid-extractable and reducible ions, which were characterized by high bioavailability. Release experiments suggested the notable Mn, Zn, As, Cr, Cu and Ni release in NaCl solution, and significant release of Mn, Zn, As, Cr, Cu, Pb and Ni in gastrointestinal solutions. The high metal release ratio in the simulated gastric solution was attributed to the weak binding of metal ions to NAMPs in acidic environment. This study will play a vital rule in assessing the ecological risks associated with MPs in natural environment.

Cucurbit[10]uril-mediated Supramolecular Assembly for Optically Tunable Dimers and Near White-light Emissive Materials.

Cucurbit[10]uril (Q[10]), the cucurbit[n]uril with a large cavity, exhibits several new features in the development of the host-guest complex. Thus, based on Q[10] and π-conjugated molecule, oligo(p-phenylenevinylene) derivative (OPVCOOH), the host-guest complexes with three different interaction ratios of 1 : 2, 2 : 2, and 3 : 2 assemblies (Q[10]: guest) were fabricated. Depending on the host/guest ratio, the emission color of these complexes ranged from blue to yellow-green. The extra Fe2+ coordinated with a bare carboxyl group of the Q[10]-OPVCOOH (3 : 2) assembly, obstructing its rotaxane structure and forming Q[10]-OPVCOOH-Fe2+ assembly, which may be used as a coating for near-white LED bulbs.

Effects of Boride Orientation and Si Content on High-Temperature Oxidation Resistance of Directionally Solidified Fe-B Alloys.

In this work, the as-cast directionally solidified (DS) Fe-B alloys with various Si contents and different boride orientation were designed and fabricated, and the as-cast microstructures and static oxidation behaviors of the DS Fe-B alloys were investigated extensively. The as-cast microstructure of the DS Fe-B alloys consists of the well-oriented Fe2B columnar grains and α-Fe, which are strongly refined by Si addition. The oxidation interface of the scales in the DS Fe-B alloy with 3.50 wt.% Si demonstrates an obvious saw-tooth shaped structure and is embedded into the alternating distributed columnar layer structures of the DS Fe-B alloy with oriented Fe2B and α-Fe matrix, which is beneficial to improve the anti-peeling performance of the oxide film compared with lower amounts of Si addition in DS Fe-B alloys with oriented Fe2B [002] orientation parallel to the oxidation direction (i.e., oxidation diffusion direction, labeled as Fe2B// sample). In the DS Fe-B alloys with oriented Fe2B [002] orientation vertical to the oxidation direction (i.e., labeled as Fe2B⟂ sample), due to the blocking and barrier effect of laminated-structure boride, Si is mainly enriched in the lower part of the oxide film to form a dense SiO2 thin layer adhered to layered boride. As a result, the internal SiO2 thin layer plays an obstructed and shielded role in oxidation of the substrate, which hinders the further internal diffusion of oxygen ions and improves the anti-oxidation performance of the Fe2B⟂ sample, making the average anti-oxidation performance better than that of the Fe2B// sample.

The Potential of Mesenchymal Stem Cells for the Treatment of Cytokine Storm due to COVID-19.

The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has seriously affected public health and social stability. The main route of the transmission is droplet transmission, where the oral cavity is the most important entry point to the body. Due to both the direct harmful effects of SARS-CoV-2 and disordered immune responses, some COVID-19 patients may progress to acute respiratory distress syndrome or even multiple organ failure. Genetic variants of SARS-CoV-2 have been emerging and circulating around the world. Currently, there is no internationally approved precise treatment for COVID-19. Mesenchymal stem cells (MSCs) can traffic and migrate towards the affected tissue, regulate both the innate and acquired immune systems, and participate in the process of healing. Here, we will discuss and investigate the mechanisms of immune disorder in COVID-19 and the therapeutic activity of MSCs, in particular human gingiva mesenchymal stem cells.

Development of Poloxamer Hydrogels Containing Antibacterial Guanidine-Based Polymers for Healing of Full-Thickness Skin Wound.

A series of hydrogels containing guanidine-based polymers using a poloxamer as the matrix were prepared to provide novel wound dressings with antibacterial and repairing-promotion properties for skin wounds. Herein, we developed a series of antibacterial hydrogels, the cationic guanidine-based polymer polyhexamethylene guanidine hydrochloride (PHMG) with poloxamer aqueous solution (12%, w/w) simplified as PHMGP, chitosan (CS)-cross-linked PHMG (referred to as PHMC) with poloxamer aqueous solution simplified as PHMCP, and hyaluronic acid (HA)-modified PHMG (referred to as PHMH) with poloxamer aqueous solution simplified as PHMHP, for enhancing full-thickness skin wound healing. The characterizations, antimicrobial activity, cytotoxicity, and in vivo full-thickness wound-healing capability of these hydrogels were analyzed and evaluated. The results show that though PHMGP possesses great bactericide properties, its cytotoxicity is too strong to support skin regeneration. However, after modified with CS or HA, PHMCP and PHMHP showed good biocompatibility and antimicrobial properties against Gram-positive and Gram-negative bacteria that are commonly present in injured skin. Both PHMCP and PHMHP hydrogels exhibited upgraded wound-healing efficiency in full-thickness skin defects, characterized by a shorter wound closure time, faster re-regeneration, and the earlier formation of skin appendages, compared with those of control or pure poloxamer treatments. Their biological mechanism was detected. Both PHMCP and PHMHP can regulate the related biofactors during the skin repair process such as interleukin-1ß (IL-1ß), interleukin-6 (IL-6), transforming growth factor beta-1(TGF-ß1), alpha-smooth muscle actin (α-SMA), and vascular endothelial growth factor, to promote wound healing with less serious scarring. In short, hydrogels with excellent capabilities to inhibit microorganism infection and promote wound healing were developed, which will shed light on designing and producing wound dressings with promising applications in future.

Cyclin G2 Inhibits Oral Squamous Cell Carcinoma Growth and Metastasis by Binding to IGFBP3 and Regulating the FAK-SRC-STAT Signaling Pathway.

The cell cycle protein cyclin G2 is considered a tumor suppressor. However, its regulatory effects and potential mechanisms in oral cancers are not well understood. This study aimed to investigate the effect of cyclin G2 on oral squamous cell carcinoma (OSCC). The data from 80 patients with OSCC were utilized to predict the abnormal expression of cyclin G2. The proliferation and metastasis were determined by a cell counting Kit-8 assay, flow cytometry, a wound-healing assay, and a cell invasion assay. The expression of key proteins and genes associated with the cyclin G2 signaling pathways was determined by western blotting and real-time PCR, respectively. The orthotopic nude mice model was established by a mouth injection of SCC9 cells overexpressing cyclin G2. We showed that the low level of cyclin G2 in OSCC, which is negatively correlated with clinical staging, was a negative prognostic factor for the disease. We also found that cyclin G2 inhibited the proliferation, metastasis, and blocked the cell cycle at G1/S of OSCC cells, suggesting that cyclin G2 has an inhibitory effect in OSCC. Mechanistically, cyclin G2 inhibited the growth and metastasis of OSCC by binding to insulin-like growth factor binding protein 3 (IGFBP3) and regulating the focal adhesion kinase (FAK) -SRC-STAT signal transduction pathway. Cyclin G2 competed with integrin to bind to IGFBP3; the binding between integrin and IGFBP3 was reduced after cyclin G2 overexpression, thereby inhibiting the phosphorylation of FAK and SRC. These results showed that cyclin G2 inhibited the progression of OSCC by interacting with IGFBP3 and that it may be a new target for OSCC treatment.