Application of bacteriophage φPaP11-13 attenuates rat Cutibacterium acnes infection lesions by promoting keratinocytes apoptosis via inhibiting PI3K/Akt pathway.

Acne vulgaris caused by antibiotic-resistant Cutibacterium acnes (C. acnes) infection is difficult to treat conventionally. Phages have been suggested as a potential solution, but research on the mechanism of phage treatment is inadequate. This research investigates the underlying molecular mechanisms of phage φPaP11-13 attenuating C. acnes-induced inflammation in rat models. We found that rats infected with C. acnes had higher average ear thickness, greater enrichment of inflammatory cells as shown by hematoxylin-eosin (HE) staining, and fewer TUNEL (TdT-mediated dUTP Nick-End Labeling)-positive keratinocytes visualized by IF staining. Moreover, an increase of IGF-1 and IGF-1 receptor (IGF-1r) was detected using the immunohistochemical (IHC) staining method, Western blot (WB), and quantitative real-time PCR (qRT-PCR) when infected with C. acnes, which was decreased after the application of phage φPaP11-13. By applying the IGF-1 antibody, it was demonstrated that the severity of C. acnes-induced inflammation was relevant to the expression of IGF-1. Through WB and qRT-PCR, activation of the PI3K/Akt pathway and a down-regulation of the BAD-mediated apoptosis pathway were discovered after C. acnes infection. Subsequently, it was shown that the activation of the PI3K/Akt pathway against BAD-mediated apoptosis pathway was alleviated after applying phage φPaP11-13. Furthermore, applying the IGF-1r inhibitor, Pan-PI3K inhibitor, and Akt inhibitor reversed the changing trends of BAD induced by C. acnes and phage φPaP11-13. This study demonstrates that one of the critical mechanisms underlying the attenuation of acne vulgaris by phage φPaP11-13 is lysing C. acnes and regulating keratinocyte apoptosis via the PI3K/Akt signaling pathway.IMPORTANCECutibacterium acnes infection-induced acne vulgaris may cause severe physical and psychological prognosis. However, the overuse of antibiotics develops drug resistance, bringing challenges in treating Cutibacterium acnes. Bacteriophages are currently proven effective in MDR (multiple drug-resistant) Cutibacterium acnes, but there is a significant lack of understanding of phage therapy. This study demonstrated a novel way of curing acne vulgaris by using phages through promoting cell death of excessive keratinocytes in acne lesions by lysing Cutibacterium acnes. However, the regulation of this cell cycle has not been proven to be directly mediated by phages. The hint of ternary relation among "phage-bacteria-host" inspires huge interest in future phage therapy studies.

TGF-ß signaling pathway in spinal cord injury: Mechanisms and therapeutic potential.

Spinal cord injury (SCI) is a highly disabling central nervous system injury with a complex pathological process, resulting in severe sensory and motor dysfunction. The current treatment modalities only alleviate its symptoms and cannot effectively intervene or treat its pathological process. Many studies have reported that the transforming growth factor (TGF)-ß signaling pathway plays an important role in neuronal differentiation, growth, survival, and axonal regeneration after central nervous system injury. Furthermore, the TGF-ß signaling pathway has a vital regulatory role in SCI pathophysiology and neural regeneration. Following SCI, regulation of the TGF-ß signaling pathway can suppress inflammation, reduce apoptosis, prevent glial scar formation, and promote neural regeneration. Due to its role in SCI, the TGF-ß signaling pathway could be a potential therapeutic target. This article reported the pathophysiology of SCI, the characteristics of the TGF-ß signaling pathway, the role of the TGF-ß signaling pathway in SCI, and the latest evidence for targeting the TGF-ß signaling pathway for treating SCI. In addition, the limitations and difficulties in TGF-ß signaling pathway research in SCI are discussed, and solutions are provided to address these potential challenges. We hope this will provide a reference for the TGF-ß signaling pathway and SCI research, offering a theoretical basis for targeted therapy of SCI.

Roles of pyroptosis in intervertebral disc degeneration.

Intervertebral disc degeneration (IDD), the key pathological process in low back pain, is characterized by chronic inflammation and progressive cell death. Pyroptosis is a type of pro-inflammatory programmed necrosis mediated by inflammasomes that is dependent on the gasdermin family of proteins. An in-depth study of the pathological mechanisms of IDD has revealed that pyroptosis plays an important role in its occurrence and development. The molecular characteristics and activation signaling mechanisms of pyroptosis are reviewed in this paper. Moreover, the specific roles of pyroptosis in IDD pathology are outlined and various targeted drugs for its treatment are highlighted.

Intrathecal Injection of Botulinum Toxin Type A has an Analgesic Effect in Male Rats CCI Model by Inhibiting the Activation of Spinal P2X4R.

Purinergic receptor P2X4 (P2X4R) plays an essential role in neuropathic pain. However, the specific mechanism needs to be clarified. Botulinum toxin type A is a neurotoxin produced by Clostridium botulinum type A. This study found that intrathecal injection of botulinum toxin type A produced an excellent analgesic effect in a rat model of chronic constriction sciatic nerve injury and inhibited the activation of P2X4R, microglia, and astrocytes. The administration of a P2X4R activator can up-regulate the expression of P2X4R and eliminate the analgesic effect of intrathecal injection of botulinum toxin type A. In addition, we found that microglia and astrocytes in the spinal cord of rats injected with botulinum toxin type A were reactivated after administration of the P2X4R activator. Our results suggest that intrathecal injection of botulinum toxin type A has an analgesic effect in a rat model of chronic constriction sciatic nerve injury by inhibiting the activation of P2X4R in the spinal cord.

Intrathecal administration of botulinum toxin type a antagonizes neuropathic pain by countering increased vesicular nucleotide transporter expression in the spinal cord of chronic constriction injury of the sciatic nerve rats.

Botulinum toxin type A (BoNT/A) induces direct analgesic effects in neuropathic pain by inhibiting the release of substance P, calcitonin gene-related peptide (CGRP) and glutamate. Vesicular nucleotide transporter (VNUT) was responsible for the storage and release of ATP in vivo, and one of the mechanisms underlying neuropathic pain is VNUT-dependent release of extracellular ATP from dorsal horn neurons. However, the analgesic effect of BoNT/A by affecting the expression of VNUT remained largely unknown. Thus, in this study, we aimed to elucidate the antinociceptive potency and analgesic mechanism of BoNT/A in chronic constriction injury of the sciatic nerve (CCI) induced neuropathic pain. Our results showed that a single intrathecal injection of 0.1 U BoNT/A seven days after CCI surgery produced significant analgesic activity and decreased the expression of VNUT in the spinal cord of CCI rats. Similarly, BoNT/A inhibited the CCI-induced increase in ATP content in the rat spinal cord. Overexpression of VNUT in the spinal cord of CCI-induced rats markedly reversed the antinociceptive effect of BoNT/A. Furthermore, 33 U/mL BoNT/A dramatically reduced the expression of VNUT in pheochromocytoma (PC12) cells but overexpressing SNAP-25 increased VNUT expression in PC12 cells. Our current study is the first to demonstrate that BoNT/A is involved in neuropathic pain by regulating the expression of VNUT in the spinal cord in rats.

Effects of substrate topography on the regulation of human fibroblasts and capsule formation via modulating macrophage polarization.

The host-material interface is critical in determining the successful integration of medical devices into human tissue. The surface topography can regulate the fibrous capsule formation around implants through macrophage polarization, but the exact mechanism remains unclear. In this study, four types of microgrooves (10 or 50 µm in groove depths and 50 or 200 µm in groove widths) were fabricated on polydimethylsiloxane (PDMS) using lithography. The microgroove surfaces were characterized using the laser scanning confocal microscopy and fourier transform infrared spectroscopy. The effect of surface topography on macrophage phenotypes and conditioned medium (CM) collected from macrophages on human foreskin fibroblast 1 (HFF-1) were investigated. The result revealed that a deeper and narrower microgroove structure means a rougher surface. Macrophages tended to adhere and aggregate on group 50-50 surface (groove depths and widths of 50 µm). THP-1 cell polarized toward both inflammatory M1 and anti-inflammatory M2 macrophages on the surface of each group. Meanwhile, CM from macrophages culture on PDMS differentially up-regulated the proliferation, migration and fibrosis of HFF-1. Among them, the group 50-50 had the strongest promoting effect. In vivo, the inflammatory response and fibrotic capsule around the implants were observed at 1 week and 4 weeks. As time passed, the inflammatory response decreased, while the capsule thickness continued to increase. The rough material surface was more inclined to develop a severe fibrotic encapsulation. In conclusion, this finding further suggested a potential immunomodulatory effect of macrophages in mediating the fibrotic response to implants and facilitated the design of biomaterial interfaces for improving tissue integration.

In Vivo and In Vitro Fibroblasts' Behavior and Capsular Formation in Correlation with Smooth and Textured Silicone Surfaces.

BACKGROUND: As the most principal complication following breast augmentation with silicone breast implants, capsular contracture is greatly influenced by surface texture. However, there have long been widespread debates on the function of smooth or textured surface implants in reducing capsular contracture. MATERIALS AND METHODS: Three commercially available silicone breast implants with smooth and textured surfaces were subjected to surface characterization, and in vitro and in vivo assessments were then implemented to investigate the effect of these different surfaces on the biological behaviors of fibroblasts and capsular formation in rat models. RESULTS: Surface characterization demonstrated that all three samples were hydrophobic with distinct roughness values. Comparing the interactions of fibroblasts or tissues with different surfaces, we observed that as surface roughness increased, the adhesion and cell spreading of fibroblasts, the level of echogenicity, the density of collagen and α-SMA-positive immunoreactivity decreased, while the proliferation of fibroblasts and capsule thickness increased. CONCLUSIONS: Our findings elucidated that the effect of silicone implant surface texture on fibroblasts' behaviors and capsular formation was associated with variations in surface roughness, and the number of myofibroblasts may have a more significant influence on the process of contracture than capsule thickness in the early stage of capsular formation. These results highlight that targeting myofibroblasts may be wielded in the prevention and treatment strategies of capsular contracture clinically. LEVEL OF EVIDENCE V: 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 .

Effect of Microgroove Structure in PDMS-Based Silicone Implants on Biocompatibility.

Capsule and capsule contracture around implants are important concerns in a clinic. The physical topology of the material surface regulates the formation of the capsule, but the specific regulatory mechanism is unclear. In this study, four types of silicone implant materials with different microgroove structures (groove depths of 10 and 50 µm and widths of 50 and 200 µm) were constructed using lithography to form different gradient surface topologies. Mass spectrometry, Cell Counting Kit-8, 5-ethynyl-2'-deoxycytidine (EdU), enzyme-linked immunosorbent assay, western blot, immunofluorescence, and immunohistochemistry were used to explore the changes in protein adsorption, cell adhesion, cell proliferation, and collagen deposition on the surface of the materials. At the same time, RNA-seq was used to detect transcriptome differences caused by different structures. Furthermore, collagen deposition and capsule formation were observed in the rats. The groove structure was observed to significantly increase the surface roughness of the material. The deeper groove and the narrower width of the polydimethylsiloxane would increase the surface roughness of the material and the surface water contact angle but reduce the total amount of adsorbed protein in the first two hours. In vitro cell experiments revealed that microtopology affected cell proliferation and adhesion and regulated collagen secretion. Further analysis indicated the deeper and narrower groove (group 50-50) on the surface of the material caused more evident collagen deposition around the material, forming a thicker envelope. Surface roughness of the material was thus related to collagen deposition and envelope thickness. The thickness of the envelope tissue around smooth materials does not exceed that of the materials with surface roughness. In conclusion, the narrower and deeper grooves in the micron range exhibited poor histocompatibility and led to formation of thicker envelopes around the materials. The appropriate grooves can reduce envelope thickness.

FoxO3a depletion accelerates cutaneous wound healing by regulating epithelial­mesenchymal transition through ß­catenin activation.

The hysteresis of keratinocyte (KC) re­epithelialization is an important factor resulting in chronic wounds; however, the molecular mechanisms involved in this cellular response remain yet to be completely elucidated. The present study demonstrated the function of transcription factor Forkhead box O3a (FoxO3a) in KC growth and migration functional effects, resulting in restrained KC re­epithelialization during wound healing. In chronic wound tissue samples, the expression of FoxO3a was significantly increased when compared with the acute wound healing group (P<0.01). Overexpressing FoxO3a significantly inhibited, whereas silencing endogenous FoxO3a enhanced, the growth and migration of HaCaT cells in vitro. Further investigation revealed that FoxO3a negatively regulated matrix metalloproteinases 1 and 9, and increased the expression of tissue inhibitor of metalloproteinase 1. In addition, the upregulation of FoxO3a retarded, whereas the downregulation of FoxO3a accelerated, transforming growth factor­ß1­induced epithelial­mesenchymal transition in HaCaT cells. Mechanistically, the overexpression of FoxO3a inactivated ß­catenin signaling and markedly reduced the levels of nuclear ß­catenin. These results reveal a novel mechanism of FoxO3a in regulating KC re­epithelialization, and provide novel targets for the prevention and treatment of chronic wounds.

Autologous Vascularization: A Method to Enhance the Antibacterial Adhesion Properties of ePTFE.

BACKGROUND: Expanded polytetrafluoroethylene (ePTFE), an ideal bioimplant material, is commonly used in surgical repair to treat soft tissue defects and deformities. However, the main disadvantage of ePTFE is that its distinctive porous ultrastructure is prone to bacterial adhesion that gives rise to infection and chronic inflammation, resulting in functional failure. Herein, a potentially promising approach to ePTFE autologous vascularization (AV-ePTFE) in vivo was established and developed to enhance the material's antibacterial properties. METHODS: Hematoxylin and eosin (H&E) staining and visual observation were performed to validate the intensity of the inflammatory response and related histological changes in surgical wounds after AV-ePTFE implantation. In addition, the antibacterial activities of AV-ePTFE were assessed by an in vitro bacterial adhesion assay and scanning electron microscope observation. RESULTS: The optimal time point of AV-ePTFE was 12 weeks after implantation. AV-ePTFE relieved inflammation based on an inflammation grading evaluation and expedited wound healing. Furthermore, AV-ePTFE effectively reduced the number of bacterial adhesions, inhibited bacterial biofilm formation, and prevented the occurrence of infection. CONCLUSIONS: We conclude that autologous vascularization is an effective method to improve the antibacterial adhesion properties and biocompatibility of ePTFE after implantation and that it may have a significant effect on clinical application of future porous biomaterials.

Negative pressure wound therapy and split thickness skin graft aided in the healing of extensive perineum necrotizing fasciitis without faecal diversion: a case report.

BACKGROUND: Perineum necrotizing fasciitis, also known as Fournier gangrene (FG), is a rare but highly mortal infectious necrotizing fasciitis with or without involvement of the underlying muscle. Evidence exists that negative pressure wound therapy (NPWT) combined with a split thickness skin graft (STSG) can help to heal wounds with FG. However, when the wound spreads to the anal area, it can easily be contaminated by faeces, causing a more extensive wounds; thus, faecal diversion is considered. Here, we report a case of extensive perineum necrotizing fasciitis that spread to near the anus; NPWT combined with STSGs was used to help heal the wound without faecal diversion. CASE PRESENTATION: A 47-year-old male patient was admitted with extensive perineum fascia necrosis caused by Pseudomonas aeruginosa that rapidly spread to near the anus. After comprehensive therapy completed wound bed preparation, STSGs from the scalp were grafted to the wound, and NPWT was applied to improve STSGs survival and seal the anus without faecal diversion. After treatment, graft take was 95%, and the exposed testicular and residual wounds were repaired with a local skin flap. At discharge, the wound had decreased to two pea-sized areas. The patient received conventional moist gauze therapy to close the residual wound at the local hospital. A follow-up by telephone 1 month later showed that both wounds had healed and that the patient was satisfied with the outcome. CONCLUSION: NPWT use combined with STSGs to cover the whole wound and the anus without faecal diversion is a safe and effective method to help with wound healing and avoid contamination with excrement.

Biofunctionalization of silicone rubber with microgroove-patterned surface and carbon-ion implantation to enhance biocompatibility and reduce capsule formation.

PURPOSE: Silicone rubber implants have been widely used to repair soft tissue defects and deformities. However, poor biocompatibility can elicit capsule formation, usually resulting in prosthesis contracture and displacement in long-term usage. To overcome this problem, this study investigated the properties of silicone rubber materials with or without a microgroove-patterned surface and with or without carbon (C)-ion implantation. MATERIALS AND METHODS: Atomic force microscopy, X-ray photoelectron spectroscopy, and a water contact angle test were used to characterize surface morphology and physicochemical properties. Cytocompatibility was investigated by a cell adhesion experiment, immunofluorescence staining, a Cell Counting Kit-8 assay, and scanning electron microscopy in vitro. Histocompatibility was evaluated by studying the inflammatory response and fiber capsule formation that developed after subcutaneous implantation in rats for 7 days, 15 days, and 30 days in vivo. RESULTS: Parallel microgrooves were found on the surfaces of patterned silicone rubber (P-SR) and patterned C-ion-implanted silicone rubber (PC-SR). Irregular larger peaks and deeper valleys were present on the surface of silicone rubber implanted with C ions (C-SR). The silicone rubber surfaces with microgroove patterns had stable physical and chemical properties and exhibited moderate hydrophobicity. PC-SR exhibited moderately increased dermal fibroblast cell adhesion and growth, and its surface microstructure promoted orderly cell growth. Histocompatibility experiments on animals showed that both the anti-inflammatory and antifibrosis properties of PC-SR were slightly better than those of the other materials, and there was also a lower capsular contracture rate and less collagen deposition around implants made from PC-SR. CONCLUSION: Although the surface chemical properties, dermal fibroblast cell growth, and cell adhesion were not changed by microgroove pattern modification, a more orderly cell arrangement was obtained, leading to enhanced biocompatibility and reduced capsule formation. Thus, this approach to the modification of silicone rubber, in combination with C-ion implantation, should be considered for further investigation and application.

The use of expanded polytetrafluoroethylene in depressed deformities of the face.

Expanded polytetrafluoroethylene (ePTFE) has been extensively used for facial soft tissue augmentation procedures, and is regarded as safe and reliable and suitable as a permanent implant. This implant is generally used in the lower third of the face for lips filling, nasal augmentation, nasolabial folds and chin augmentation, and rarely for congenital or acquired depressed deformities of the face. The aim of the present study was to assess the effects of ePTFE in congenital or acquired depressed deformities of the face. From September, 2008 to January, 2014, 26 patients were implanted with the material ePTFE to correct depressed deformities of the face. The average age at operation was 23.2 years, with a range of 17-45 years. The depressed deformities were lateralized. The follow-up period was 6-18 months (average 9 months). The etiologies of the depressed deformities included stable hemifacial atrophy (3 cases), craniofacial microsomia (13 cases), bony depression after trauma (8 cases), and other unclear reasons (2 cases). The operations were performed under local anesthesia. ePTFE was inserted in different tissue planes that varied among the different subanatomical areas in the face: beneath the superficial temporal fascia in the temporal area, and on the surface of the superficial musculoaponeurotic system in the zygomatic area, cheek and mandibular area. All of the patients were followed up. Most of the patients [25 of 26 patients (96.2%)] were satisfied with the results, while 1 patient (3.8%) was not satisfied for incomplete correction of the depressed deformity. In conclusion, aside from lipofilling and a free flap transfer, the results showed that ePTFE was an alternative treatment for facial depressed deformity.

Complications from Nasolabial Fold Injection of Calcium Hydroxylapatite for Facial Soft-Tissue Augmentation: A Systematic Review and Meta-Analysis.

BACKGROUND: Despite its increasing usage of facial applications, there is a paucity of objective data regarding calcium hydroxylapatite (CaHA). OBJECTIVES: To systematically evaluate the complications from CaHA injection for facial soft tissue augmentation. METHODS: Published studies on CaHA injection for facial soft tissue enhancement were identified through searches of the PubMed, EMBASE, and Cochrane Controlled Trial databases. Only randomized, controlled trials comparing CaHA injection to either placebo or an active comparator for facial cosmetic use were included. The outcome measures were the count (n) and frequency (%) of each complication, including edema (swelling), erythema (redness), ecchymosis (bruising), pain, pruritus (itching), hematomas, nodules, and extrusions. RESULTS: Four studies on nasolabial fold (NLF) injection of CaHA consisting of two subgroups were included: (i) a CaHA-lidocaine vs CaHA subgroup and (ii) a CaHA vs hyaluronic acid (HA) subgroup. The addition of lidocaine to CaHA therapy displayed no significant effect on edema (RR (95% CI): 1.07 (0.94-1.21), P = .311), erythema (RR (95% CI): 0.91 (0.66-1.24), P = .544), ecchymosis (RR (95% CI): 1.04 (0.71-1.52), P = .843), pain (RR (95% CI): 0.88 (0.58-1.33), P = .553), or pruritus (RR (95% CI): 0.82 (0.45-1.50), P = .515). There was no significant difference between CaHA vs HA for hematomas (RR (95% CI): 0.24 (0.01-4.31), P = .332) or nodules (RR (95% CI): 0.18 (0.01-6.62), P = .353). There was no significant publication bias detected in either subgroup (Begg's test P > 0.05). CONCLUSIONS: These findings support the addition of lidocaine to NLF injection of CaHA and suggest an equivalence between CaHA and HA with respect to hematoma and nodule formation. LEVEL OF EVIDENCE 2: Risk.

Contribution of glutathione S-transferase gene polymorphisms to development of skin cancer.

BACKGROUND: Glutathione S-transferase (GST) family genes are of vital importance in maintaining cellular defence systems, protecting cells against the toxic effects of reactive oxygen produced during the synthesis of melanin, and detoxifying environmental mutagens and chemical or synthetic drugs. As no previous meta-analyses have examined the association of polymorphisms at GSTT1, GSTP1 Ile105Val with skin cancer risk and independently published studies have produced inconsistent conclusions, we were promoted to estimate the associations in the largest study to date. METHODS: Computer-assisted searches were carried out to systematically identify the studies of GST polymorphisms and skin cancer. The eligibility of studies was evaluated following the requirements of inclusion criteria. Risk of skin cancers (OR and 95% CI) was assessed with the fixed or random effects meta-analysis. MAJOR FINDINGS: The fixed effects meta-analysis of 15 studies suggested no overall association between GSTT1 null and skin cancer. Nor was there a significant association in any subgroup. However, in the stratified analysis by histologic type for GSTP1 Ile105Val, we found 1.56 times higher risk of malignant melanoma (MM) among people with the 105-Val/Val genotype (Val/Val vs. Ile/Ile: OR = 1.56, 95% CI = 1.05-2.32, pheterogeneity = 0.584). CONCLUSIONS: These statistical data demonstrate that Ile105Val polymorphism of the GSTP1 gene may have genetic contribution to the development of skin cancer, MM in particular.

Hydroxyapatite-coated sillicone rubber enhanced cell adhesion and it may be through the interaction of EF1ß and γ-actin.

Silicone rubber (SR) is a common soft tissue filler material used in plastic surgery. However, it presents a poor surface for cellular adhesion and suffers from poor biocompatibility. In contrast, hydroxyapatite (HA), a prominent component of animal bone and teeth, can promote improved cell compatibility, but HA is an unsuitable filler material because of the brittleness in mechanism. In this study, using a simple and economical method, two sizes of HA was applied to coat on SR to counteract the poor biocompatibility of SR. Surface and mechanical properties of SR and HA/SRs confirmed that coating with HA changes the surface topology and material properties. Analysis of cell proliferation and adhesion as well as measurement of the expression levels of adhesion related molecules indicated that HA-coated SR significantly increased cell compatibility. Furthermore, mass spectrometry proved that the biocompatibility improvement may be related to elongation factor 1-beta (EF1ß)/γ-actin adjusted cytoskeletal rearrangement.

Osteopontin (OPN) is an important protein to mediate improvements in the biocompatibility of C ion-implanted silicone rubber.

Medical device implants are drawing increasing amounts of interest from modern medical practitioners. However, this attention is not evenly spread across all such devices; most of these implantable devices can cause adverse reactions such as inflammation, fibrosis, thrombosis, and infection. In this work, the biocompatibility of silicone rubber (SR) was improved through carbon (C) ion implantation. Scanning electron microscopy (SEM), atomic force microscopy (AFM), X-ray photoelectron spectroscopy (XPS), and X-ray diffraction (XRD) results confirmed that these newly generated carbon-implanted silicone rubbers (C-SRs) had large, irregular peaks and deep valleys on their surfaces. The water contact angle of the SR surface decreased significantly after C ion implantation. C ion implantation also changed the surface charge distribution, silicone oxygen rate, and chemical-element distribution of SR to favor cell attachment. The dermal fibroblasts cultured on the surface C-SR grew faster and showed more typical fibroblastic shapes. The expression levels of major adhesion proteins, including talin-1, zyxin, and vinculin, were significantly higher in dermal fibroblasts cultured on C-SR coated plates than in dermal fibroblasts cultured on SR. Those same dermal fibroblasts on C-SRs showed more pronounced adhesion and migration abilities. Osteopontin (OPN), a critical extracellular matrix (ECM) protein, was up-regulated and secreted from dermal fibroblasts cultured on C-SR. Matrix metalloproteinase-9 (MMP-9) activity was also increased. These cells were highly mobile and were able to adhere to surfaces, but these abilities were inhibited by the monoclonal antibody against OPN, or by shRNA-mediated MMP-9 knockdown. Together, these results suggest that C ion implantation significantly improves SR biocompatibility, and that OPN is important to promote cell adhesion to the C-SR surface.

Genetic association between p53 codon 72 polymorphism and risk of cutaneous squamous cell carcinoma.

This study was designed to obtain a conclusive result about the relevance of p53 codon 72 polymorphism to the risk of cutaneous squamous cell carcinoma (SCC). We performed an updated meta-analysis of 3,792 subjects (1,349 cancer cases and 2,443 controls) to summarize the data available for p53 codon 72 polymorphism and SCC risk. The association was estimated by odds ratios (ORs) with 95% confidence intervals (CIs). The meta-analysis showed no statistical significance for SCC risk associated with any of the genetic models of p53 codon 72 polymorphism. The analyses by ethnic subgroup also failed to produce significant associations. This study suggests that p53 codon 72 polymorphism does not appear to represent a significant susceptibility factor for SCC in Caucasians.