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 .

Mechanisms Affecting Physical Aging and Swelling by Blending an Amphiphilic Component.

Polymer blending is a promising method to overcome stability obstacles induced by physical aging and swelling of implant scaffolds prepared from amorphous polymers in biomedical application, since it will not bring potential toxicity compared with chemical modification. However, the mechanism of polymer blending still remains unclearly explained in existing studies that fail to provide theoretical references in material R&D processes for stability improvement of the scaffold during ethylene oxide (EtO) sterilization, long-term storage, and clinical application. In this study, amphiphilic poly(ethylene glycol)-co-poly(lactic acid) (PELA) was blended with amorphous poly(lactic-co-glycolic acid) (PLGA) because of its good miscibility so as to adjust the glass transition temperature (Tg) and hydrophilicity of electrospun PLGA membranes. By characterizing the morphological stability and mechanical performance, the chain movement and the glass transition behavior of the polymer during the physical aging and swelling process were studied. This study revealed the modification mechanism of polymer blending at the molecular chain level, which will contribute to stability improvement and performance adjustment of implant scaffolds in biomedical application.

Rapid colonization and biodegradation of untreated commercial polyethylene wrap by a new strain of Bacillus velezensis C5.

Biodegradation could be a potential alternative solution to polyethylene (PE) pollution. However, its hydrophobic surface and long carbon chains make extremely low biodegradation efficiency. In this study, we screened a novel potential bacterial strain C5 (CGMCC number: 1.18715) for low-density polyethylene (LDPE) biodegrading from landfills. The strain was identified as Bacillus velezensis according to its 16S rRNA sequence. The contact angle analysis indicated that C5 could rapidly form biofilm on untreated LDPE which resulted in contact angles decreasing from 100° to 54° over 7 d. After the LDPE film incubated with C5 for 90 d, the thickness and weight of LDPE film decreased by 26% and 8.01%, respectively. Besides, the biotreated PE film was found with increases in weight-averaged molecular weight by 29.8%, suggesting low molar mass chains were consumed. C24-C29 n-alkanes were detected in the biodegradation products, which proved the depolymerization of LDPE. Combined with the genome mining results, a possible biofilm-aided degrading mechanism was proposed and might involve key enzymes, such as laccase, cytochrome P450 and propionyl-CoA carboxylase, which could constitute a multienzyme system for the co-catalytic degradation of LDPE waste.

Topical effect of benzalkonium bromide on wound healing and potential cellular and molecular mechanisms.

Benzalkonium bromide (BB) has been widely used as a skin antiseptic for wound management. However, BB had proinflammation and reactive oxygen species (ROS) induction effect, making its role in wound healing complex and unclear. A rat full-thickness skin defect wound model was established. The effects of BB, povidone iodine (PVP-I), chlorhexidine gluconate (CHG), and normal saline (NS) on wound healing and infection control were then evaluated based on wound healing rate (WHr) and bacterial killing. The wound tissues were sectioned for histopathological evaluation and nuclear factor E2 related factor 2 (Nrf2) expression determination. The ROS production, Nrf2 activation, and heme oxygenase 1 (HO-1) expression of the HaCat cells and the cytotoxicity treated with BB were further explored. Compared with NS, PVP-I, and CHG, BB showed the best wound infection control efficiency while delayed wound healing with the WHr of 91.42 ± 5.12% at day 20. The wound tissue of the BB group showed many inflammatory cells but few granulation tissue and capillaries and no obvious collagen deposition, resulting in the lowest histopathological scores of 4.17 ± 0.75 for BB group. BB showed higher cytotoxicity on HaCat cells with the lowest IC25, IC50, and IC75 of 1.90, 4.16, and 9.09 g/mL compared with PVP-I and CHG. TUNEL staining evaluated the cytotoxicity of BB on wound tissue, which indicates the high apoptosis index BB group (5.05 ± 1.77). Compared with PVP-I and CHG, BB induced much more cell apoptosis. The results of flow cytometry and fluorescence staining showed that PVP-I, CHG, and BB induced ROS production in a concentration-dependent manner and cells treated with BB had the highest ROS production at the same inhibition concentration. The cells and the wound tissues treated with BB showed highest Nrf2 activation and HO-1 expression than PVP-I and CHG. BB was highly efficient in wound infection control while delayed wound healing. The prolonged and strengthened inflammation and the raised ROS production originating from BB administration may contribute to delayed wound healing.

Chemical Stability and Antimicrobial Activity of Plasma-Sprayed Cerium Oxide-Incorporated Calcium Silicate Coating in Dental Implants.

PURPOSE: The aim of this study is to investigate the biological activity and antibacterial property of cerium oxide-incorporated calcium silicate coatings (CeO2-CS) in dental implants. MATERIALS AND METHODS: In this study, MC3T3-E1 cells cultured on the plastic, Ti-6Al-4V, and the cerium oxide-incorporated calcium silicate coatings (CeO2-CS) coating served as the blank, control, and CeO2-CS groups, respectively. A cell counting kit-8 (CCK-8) and flow cytometry were used to evaluate the biocompatibility. The osteoblastic differentiation of the MC3T3-E1 cells was also analyzed by quantitative real-time polymerase chain reaction analysis. The CCK-8 and counts of colony-forming units (CFUs) were used to detect the antibacterial activity of the coating on Enterococcus faecalis. The study showed that the cerium oxide-incorporated calcium silicate coating (CeO2-CS) has better biocompatibility. Meanwhile, the ALP, OCN, and BSP mRNA expression levels in the CeO2-CS group were significantly upregulated (P < 0.05). The number of viable bacteria and the CFU results were significantly reduced in the CeO2-CS group (P < 0.05). CONCLUSION: The cerium oxide-incorporated calcium silicate coatings (CeO2-CS) may promote the osteoblastic differentiation of osteoblasts. Meanwhile, the cerium oxide-incorporated calcium silicate coating (CeO2-CS) showed strong antimicrobial activity on E. faecalis, with good biocompatibility.

Porous PVDF/PANI ion-exchange membrane (IEM) modified by polyvinylpyrrolidone (PVP) and lithium chloride in the application of membrane capacitive deionisation (MCDI).

In this work, polyvinylidene fluoride (PVDF)/polyaniline (PANI) heterogeneous anion-exchange membranes filled with pore-forming agents polyvinylpyrrolidone (PVP) and lithium chloride were prepared by the solution-casting technique using the solvent 1-methyl-2-pyrrolidone (NMP) and a two-step phase inversion procedure. Key properties of the as-prepared membranes, such as hydrophilicity, water content, ion exchange capacity, fixed ion concentration, conductivity and transport number were examined and compared between membranes in different conditions. The pore-forming hydrophilic additives PVP and lithium chloride to the casting solution appeared to improve the ion-exchange membranes (IEMs) by increasing the conductivity, transport number and hydrophilicity. The effects of increasing membrane drying time on the porosity of the as-prepared membranes were found to lower membrane porosity by reducing membrane water content. However, pore-forming agents were found to be able to stabilise membrane transport number with different drying times. As-prepared PVDF/PANI anion-exchange membrane with pore-forming agent is demonstrated to be a more efficient candidate for water purification (e.g. desalination) and other industrial applications.

Expression of the MYB transcription factor gene BplMYB46 affects abiotic stress tolerance and secondary cell wall deposition in Betula platyphylla.

Plant MYB transcription factors control diverse biological processes, such as differentiation, development and abiotic stress responses. In this study, we characterized BplMYB46, an MYB gene from Betula platyphylla (birch) that is involved in both abiotic stress tolerance and secondary wall biosynthesis. BplMYB46 can act as a transcriptional activator in yeast and tobacco. We generated transgenic birch plants with overexpressing or silencing of BplMYB46 and subjected them to gain- or loss-of-function analysis. The results suggest that BplMYB46 improves salt and osmotic tolerance by affecting the expression of genes including SOD, POD and P5CS to increase both reactive oxygen species scavenging and proline levels. In addition, BplMYB46 appears to be involved in controlling stomatal aperture to reduce water loss. Overexpression of BplMYB46 increases lignin deposition, secondary cell wall thickness and the expression of genes in secondary cell wall formation. Further analysis indicated that BplMYB46 binds to MYBCORE and AC-box motifs and may directly activate the expression of genes involved in abiotic stress responses and secondary cell wall biosynthesis whose promoters contain these motifs. The transgenic BplMYB46-overexpressing birch plants, which have improved salt and osmotic stress tolerance, higher lignin and cellulose content and lower hemicellulose content than the control, have potential applications in the forestry industry.

Surface changes of nanotopography by carbon ion implantation to enhance the biocompatibility of silicone rubber: an in vitro study of the optimum ion fluence and adsorbed protein.

Lower cellular adhesion and dense fibrous capsule formation around silicone breast implants caused by lower biocompatibility is a serious clinical problem. Preliminary work has shown that ion implantation enhances cell adhesion. Whether the biocompatibility is further enhanced by higher doses of carbon ion implantation and the mechanism by which ion implantation enhances biocompatibility remain unclear. In this study, five doses of carbon ions, which gradually increase, were implanted on the surface of silicone rubber and then the surface characteristics were surveyed. Then, cell adhesion, proliferation and migration were investigated. Furthermore, the vitronectin (VN) protein was used as a model protein to investigate whether the ion implantation affected the adsorbed protein on the surface. The obtained results indicate that enhanced cytocompatibility is dose dependent when the doses of ion implantation are less than 1 × 1016 ions/cm2. However, when the doses of ion implantation are more than 1 × 1016 ions/cm2, enhanced cytocompatibility is not significant. In addition, surface physicochemical changes by ion implantation induced a conformational change of the adsorbed vitronectin protein that enhanced cytocompatibility. Together, these results suggest that the optimum value of carbon ion implantation in silicone rubber to enhance biocompatibility is 1 × 1016 ions/cm2, and ion implantation regulates conformational changes of adsorbed ECM proteins, such as VN, and mediates the expression of intracellular signals that enhance the biocompatibility of silicone rubber. The results herein provide new insights into the surface modification of implant polymer materials to enhance biocompatibility. It has potentially broad applications in the biomedical field.

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.

Salivary and serum inflammatory mediators among pre-conception women with periodontal disease.

BACKGROUND: There have been inconsistent conclusions regarding the levels of inflammatory mediators in saliva and serum among people with or without periodontal disease. Although pre-conception has been put forward as the optimal time for the periodontal treatment in order to improving pregnancy outcomes, few studies have been conducted to examine inflammatory mediators in saliva and serum among pre-conception women. METHODS: Pre-conception women were recruited between January 2012 and December 2014. Women were provided with an oral health examination to detect periodontal disease. Salivary and serum samples were collected at the same of examination. Inflammatory mediators includinginterleukin-1 beta (IL-1ß), IL-6, tumor necrosis factor alpha (TNF-α) and beta-glucuronidase (ß-glucuronidase) were tested and analyzed among women with overall periodontal disease (n = 442) or moderate/severe periodontal disease (n = 247). Results were compared to that in women with a healthy periodontium (n = 91). RESULTS: Significantly increased concentrations of inflammatory mediators of IL-1ß, IL-6, TNF-α and ß-glucuronidase in saliva and IL-1ß, ß-glucuronidase and TNF-α in serum were found among pre-conception women with moderate/severe periodontal disease, compared with women without periodontal disease. Significantly increased levels were also found in all the above saliva inflammatory mediators and in serum IL-1ß and TNF-α among women with overall periodontal disease. The levels of all inflammatory mediators in saliva and almost all inflammatory mediators except IL-6 in serum significantly increased with severity of periodontal disease. CONCLUSION: Periodontal disease is highly associated with the elevated levels of inflammatory mediators in saliva and some mediators in serum among pre-conception women.

High performance enrichment and analysis of fluoroquinolones residues in environmental water using cobalt ion mediated paper-based molecularly imprinted polymer chips.

BACKGROUND: Fluoroquinolones (FQs) are widely used for their excellent antimicrobial properties, yet their release into aquatic environments pose risks to ecosystems and public health. The accurate monitoring and analysis of FQs present challenges due to their low concentrations and the complex matrices found in actual environmental samples. To address the need for auto-pretreatment and on-line instrumental analysis, developing new microextraction materials and protocols is crucial. Such advancements will provide better analytical assurance for the effective extraction and determination of FQs at trace levels, which is of great significance to environmental protection and human health. RESULTS: In this work, we presented a Co2+ mediated paper-based molecularly imprinted polymer chip (CMC@Co-MIP), combined with UPLC analysis, to develop an effective analytical method for identifying and quantifying trace amounts of ciprofloxacin (CIP) and enrofloxacin (ENR) in water samples. Notably, the addition of Co2+ in CMC@Co-MIP helped to capture the template molecule CIP through coordination before imprinting, which significantly improved the ordering of the imprinted cavities. CMC@Co-MIP exhibited a maximum adsorption capacity up to 500.20 mg g-1 with an imprinting factor of 4.12, surpassing previous reports by a significant margin. Furthermore, the enrichment mechanism was extensively analyzed by various characterization techniques. The developed method showed excellent repeatability and reproducibility (RSD < 13.0 %) with detection limits ranging from 0.15 to 0.21 µg L-1 and recoveries ranging from 64.9 % to 102.3 % in real spiked water samples. SIGNIFICANCE: We developed a novel microextraction paper-based chip based on Co2+ mediation, which effectively improved the selectivity and convenience of extracting FQs. This breakthrough allowed the chip to have a high enrichment efficiency as well as provide a robust on-line instrumental program. It also confirms that the imprinting scheme based on metal ion coordination is a high-performance strategy.

Molecular Mechanisms Underlying the Effects of Small Intestinal Fermentation on Enhancement of Prebiotic Characteristics of Cellulose in the Large Intestine.

Knowledge about the prebiotic characteristics of cellulose by in vitro fermentation is not complete due to the neglect of small intestinal fermentation. This study investigated the effects of small intestinal fermentation on the prebiotic characteristics of cellulose in the large intestine and potential mechanisms through an approach of combined in vivo small intestinal fermentation and in vitro fermentation. The structural similarity between cellulose in feces and after processing by the approach of this study confirmed the validity of the approach employed. Results showed that small intestinal fermentation of cellulose increased both acetate and propionate content and enriched Corynebacterium selectively. Compared to in vitro fermentation after in vitro digestion of cellulose, the in vitro fermentation of cellulose after in vivo small intestinal fermentation produced higher contents of acetate and propionate as well as the abundance of probiotics like Ruminococcaceae_UCG-002, Blautia, and Bifidobaterium. The changes in the structural features of cellulose after in vivo small intestinal fermentation were more obvious than those after in vitro digestion, which may account for the greater production of short-chain fatty acids (SCFAs) and the abundance of probiotics. In summary, small intestinal fermentation enhanced the prebiotic characteristics of cellulose in the large intestine by predisrupting its structure.

Polyphenol-mediated redox-active hydrogel with H2S gaseous-bioelectric coupling for periodontal bone healing in diabetes.

Excessive oxidative response, unbalanced immunomodulation, and impaired mesenchymal stem cell function in periodontitis in diabetes makes it a great challenge to achieve integrated periodontal tissue regeneration. Here, a polyphenol-mediated redox-active algin/gelatin hydrogel encapsulating a conductive poly(3,4-ethylenedioxythiopene)-assembled polydopamine-mediated silk microfiber network and a hydrogen sulfide sustained-release system utilizing bovine serum albumin nanoparticles is developed. This hydrogel is found to reverse the hyperglycemic inflammatory microenvironment and enhance functional tissue regeneration in diabetic periodontitis. Polydopamine confers the hydrogel with anti-oxidative and anti-inflammatory activity. The slow, sustained release of hydrogen sulfide from the bovine serum albumin nanoparticles recruits mesenchymal stem cells and promotes subsequent angiogenesis and osteogenesis. Moreover, poly(3,4-ethylenedioxythiopene)-assembled polydopamine-mediated silk microfiber confers the hydrogel with good conductivity, which enables it to transmit endogenous bioelectricity, promote cell arrangement, and increase the inflow of calcium ion. In addition, the synergistic effects of hydrogen sulfide gaseous-bioelectric coupling promotes bone formation by amplifying autophagy in periodontal ligament stem cells and modulating macrophage polarization via lipid metabolism regulation. This study provides innovative insights into the synergistic effects of conductivity, reactive oxygen species scavenging, and hydrogen sulfide on the periodontium in a hyperglycemic inflammatory microenvironment, offering a strategy for the design of gaseous-bioelectric biomaterials to promote functional tissue regeneration in immune-related diseases.

A randomized controlled trial of pre-conception treatment for periodontal disease to improve periodontal status during pregnancy and birth outcomes.

BACKGROUND: Evidence has suggested that periodontal disease is associated with an increased risk of various adverse pregnancy and birth outcomes. However, several large clinical randomized controlled trials failed to demonstrate periodontal therapy during pregnancy reduced the incidence of adverse pregnancy and birth outcomes. It has been suggested that the pre-conception period may be an optimal period for periodontal disease treatment rather than during pregnancy. To date, no randomized controlled trial (RCT) has examined if treating periodontal disease before pregnancy reduces adverse birth outcomes. This study aims to examine if the pre-conception treatment of periodontal disease will lead to improved periodontal status during late pregnancy and subsequent birth outcomes. METHODS/DESIGN: A sample of 470 (235 in each arm of the study) pre-conception women who plan to conceive within one year and with periodontal disease will be recruited for the study. All participants will be randomly allocated to the intervention or control group. The intervention group will receive free therapy including dental scaling and root planning (the standard therapy), supragingival prophylaxis, and oral hygiene education. The control group will only receive supragingival prophylaxis and oral hygiene education. Women will be followed throughout their pregnancy and then to childbirth. The main outcomes include periodontal disease status in late pregnancy and birth outcomes measured such as mean birth weight (grams), and mean gestational age (weeks). Periodontal disease will be diagnosed through a dental examination by measuring probing depth, clinical attachment loss and percentage of bleeding on probing (BOP) between gestational age of 32 and 36 weeks. Local and systemic inflammatory mediators are also included as main outcomes. DISCUSSION: This will be the first RCT to test whether treating periodontal disease among pre-conception women reduces periodontal disease during pregnancy and prevents adverse birth outcomes. If the effect of pre-pregnancy periodontal treatment is confirmed, this intervention could be recommended for application in low- or middle-income countries to improve both oral health and maternal and child health. TRIAL REGISTRATION: This trial is registered with Chinese Clinical Trial Registry (ChiCTR): ChiCTR-TRC-12001913.

[Effectiveness assessment of 3-D cone beam CT used in human bite marks identification].

The present study was aimed to use the 3-D cone beam CT (CBCT) as a new method in human bite marks identification which was carried out in experimental pigskin to assess its effectiveness in our laboratory. Bite marks were digital photographed according to American Board of Forensic Odontology (ABFO) guidelines. In this study, the data of the suspect's dental casts were collected by scanning in two ways: one was after plate scanning, in which the comparison overlays were generated by Adobe Photoshop 8.0 software; the other was by CBCT, which generated comparison overlays automatically. The bite marks were blind identified with the two kinds of data of the suspect's dental casts respectively. ROC curve was used to analyze the sensitivity, specificity, and 95% confidence interval. The results showed that CBCT method got a larger area under the ROC curve: 0.784 (SE = 0.074, 95% CI = 0.639-0.929), and got a very high specificity (specificity 98.7%, 95% CI = 94.5%-99.8%). Thus, this study illustrates that the CBCT used in bite mark identification is an effective and accurate tool and has stronger ability to exclude suspects compared with the conventional method, but the comparison process needs further study to enhance its effectiveness in bite mark identification.

Preparation of a Cellulosic Photosensitive Hydrogel for Tubular Tissue Engineering.

Since the concept of tissue engineering was proposed, biocompatible hydrogel materials have attracted the attention of researchers. With the help of three-dimensional (3D) printing technology, precise shaping of hydrogels can be realized. In this paper, we synthesized a cellulosic photosensitive acrylamide (AM)/N,N-methylenebisacrylamide (MBA) hydrogel. With the high-efficiency water-soluble photoinitiator TPO@Tw developed by our research group, the efficient photocuring cross-linking process of the hydrogel can be realized under 405 nm visible light. In consideration of the viscosity, curing mass, curing depth, and break distance of the hydrogel, we screened out hydroxypropyl cellulose (HPC) as the preferred tackifier of the material. The addition of HPC greatly improved the mechanical properties of the hydrogel. The compressive modulus of the optimal sample AM-HPC-5 increased by 709.2% and the tensile strength increased by 76.7% compared with the blank control group. By adding a PEGDA shell to the surface of the material, the water retention capacity of the hydrogel was effectively improved. The water loss rate was greatly reduced. The 3D wooden-pile structure model was printed by a DIW 3D printer. Further, through coaxial extrusion, the microtubule structure that may be applied in tissue engineering was obtained. Cell experiment results showed high biocompatibility of the hydrogel. NIH 3T3 cells could adhere and grow on the surface of microtubules.

A Biomimetic Nanogel System Restores Macrophage Phagocytosis for Magnetic Resonance Imaging-Guided Synergistic Chemoimmunotherapy of Breast Cancer.

Novel strategies to facilitate tumor-specific drug delivery and restore immune attacks remain to be developed to overcome the current limitations of chemotherapy. Herein, a cancer cell membrane (CM)-camouflaged and ultrasmall iron oxide nanoparticles (USIO NPs)-loaded polyethylenimine nanogel (NG) system is reported to co-deliver docetaxel (DTX) and CD47 siRNA (siCD47). The prepared co-delivery system exhibits good colloidal stability, biocompatibility, and r1 relaxivity (1.35 mM-1 s-1 ) and enables redox-responsive release of the loaded DTX in the tumor microenvironment. The NG system realizes homologous targeting delivery of DTX and siCD47 to murine breast cancer cells (4T1 cells) for efficient chemotherapy and gene silencing; thus, inducing immunogenic cell death (ICD) and restoring macrophage phagocytic effect through downregulation of "don't eat me" signals on cancer cells. Likewise, the co-delivery system can also act on macrophages to promote their M1 polarization, which can be combined with DTX-mediated ICD and antibody-mediated immune checkpoint blockade to generate effector T cells for robust chemoimmunotherapy. Further, the USIO NPs-incorporated NG system also allows for magnetic resonance imaging of tumors. The developed biomimetic NG system acting on both cancer cells and macrophages holds a promising potential for macrophage phagocytosis-restored chemoimmunotherapy.

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.

Porphyromonas gingivalis induced UCHL3 to promote colon cancer progression.

Porphyromonas gingivalis (P. gingivalis), a Gram-negative oral anaerobe, was demonstrated to facilitate colonization and progression in colonic tumor, while the underlying mechanism still remains to be clarified. Here, we identified the proteome profile changed by P. gingivalis infection in HCT116 cells through label-free quantitative proteomics, and found that deubiquitinase UCHL3 was a key protein that response for P. gingivalis infection. By CCK8, colony formation, wound healing assays, and in vivo subcutaneous tumor mouse moudle, we proved that P. gingivalis could promote the proliferation and migration of colon cancer, while the process was inhibited by UCHL3 knock down. Through IP-MS, we identified GNG12 as the UCHL3 interacting protein. The protein level of GNG12 was significantly reduced when knock out UCHL3. Thus we propose that GNG12 is a substrate protein of UCHL3. Furthermore, we demonstrated that overexpression of GNG12 could restore the tumor inhibition effect caused by UCHL3 knock down, and UCHL3-GNG12 axis promote colon cancer progression via the NF-κB signal pathway. Collectively, this study unveiled that P. gingivalis infection up-regulated UCHL3 and stabilized its substrate protein GNG12 to activate the NF-κB signal pathway to promote colon cancer progression. Our study indicate that UCHL3 is a potential biomarker and therapeutic target for colon cancer which infected with P. gingivalis.

A protocol to induce systemic autophagy and increase energy metabolism in mice using PEGylated arginine deiminase.

Obesity is a prevalent metabolic disorder worldwide. Here, we describe a comprehensive protocol using pegylated arginine deiminase (ADI-EPG 20) to apply the concept that arginine depletion induces systemic autophagy to drive whole-body energy metabolism and weight loss in mice. We detail the steps for cohort setup, mouse husbandry, and treatment and provide expected results under these conditions. For complete details on the use and execution of this protocol, please refer to Zhang et al. (2022a, 2022b).