A pleiotropic role of sialidase in the pathogenicity of Porphyromonas gingivalis.

As one of the keystone pathogens of periodontitis, the oral bacterium Porphyromonas gingivalis produces an array of virulence factors, including a recently identified sialidase (PG0352). Our previous report involving loss-of-function studies indicated that PG0352 plays an important role in the pathophysiology of P. gingivalis. However, this report had not been corroborated by gain-of-function studies or substantiated in different P. gingivalis strains. To fill these gaps, herein we first confirm the role of PG0352 in cell surface structures (e.g., capsule) and serum resistance using P. gingivalis W83 strain through genetic complementation and then recapitulate these studies using P. gingivalis ATCC33277 strain. We further investigate the role of PG0352 and its counterpart (PGN1608) in ATCC33277 in cell growth, biofilm formation, neutrophil killing, cell invasion, and P. gingivalis-induced inflammation. Our results indicate that PG0352 and PGN1608 are implicated in P. gingivalis cell surface structures, hydrophobicity, biofilm formation, resistance to complement and neutrophil killing, and host immune responses. Possible molecular mechanisms involved are also discussed. In summary, this report underscores the importance of sialidases in the pathophysiology of P. gingivalis and opens an avenue to elucidate their underlying molecular mechanisms.

Nanoplastics exposure-induced mitochondrial dysfunction contributes to disrupted stem cell differentiation in human cerebral organoids.

Nanoplastics are ubiquitous in our daily lives, raising concerns about their potential impact on the human brain. Many studies reported that nanoplastics permeate the blood-brain barrier and influence cellular processes in mouse models. However, the neurotoxic effects of ingesting nanoplastics on human brain remain poorly understood. Here, we treated cerebral organoids with polystyrene nanoplastics to model the effects of nanoplastic exposure on human brain. Importantly, we found that mitochondria might be the significant organelles affected by polystyrene nanoplastics using immunostaing and RNA-seq analysis. Subsequently, we observed the increased cell death and decreased cell differentiation in our cerebral organoids. In conclusion, our findings shed insights on the mechanisms underlying the toxicity of nanoplastics on human brain organoids, providing an evaluation system in detection potential environmental toxicity on human brain.

In vitro study of the treatment of dentin hypersensitivity with gallic acid combined with sodium fluoride.

BACKGROUND: Dentin hypersensitivity (DH) is a common oral condition that is associated with severe dental pain. Pain relief is a key focus of the treatment of DH. The purpose of this study was to evaluate the blocking and antacid effects of gallic acid (GA) combined with sodium fluoride (NaF) on dentinal tubules in vitro. METHODS: Ninety dentin discs from human third molars were treated with 6% citric acid for 2 min. Then, the surface morphologies of ten dentin discs were observed by scanning electron microscopy (SEM). The remaining samples were randomly divided into four groups: the NaF group, which was treated with 1000 ppm NaF; the GA group, which was treated with 4000 ppm GA; the GA + NaF group, which was treated with 1000 ppm NaF + 4000 ppm GA; and the blank group, which was treated with deionized water. The dentin permeability of each sample was measured with a water-filled system before processing and after 7 days of treatment. Dentin morphology and surface deposits were observed by SEM. Then, samples from the NaF, GA + NaF and blank groups were subjected to an acid challenge by incubation with 0.02% citric acid for 2 min. SEM and a water-filled system were used to evaluate the blocking and antacid effects of NaF and GA + NaF. RESULTS: 1. NaF and GA + NaF significantly decreased dentin permeability. The effect of the GA + NaF treatment was more significant. After acid challenge, both groups still exhibited decreased dentin permeability compared with the initial assessment. 2. Compared with the NaF group, the GA + NaF group had more mineral deposits on the dentin surface and dentin tubules. After acid challenge, the deposits in the GA + NaF group were still clearly visible. CONCLUSION: The combined effect of GA and NaF on reducing dentin permeability by blocking open dentin tubules is better than that of NaF alone. After acid challenge, the GA + NaF treatment still had a better effect.

SGK1 negatively regulates inflammatory immune responses and protects against alveolar bone loss through modulation of TRAF3 activity.

Serum- and glucocorticoid-regulated kinase 1 (SGK1) is a serine/threonine kinase that plays important roles in the cellular stress response. While SGK1 has been reported to restrain inflammatory immune responses, the molecular mechanisms involved remain elusive, especially in oral bacteria-induced inflammatory milieu. Here, we found that SGK1 curtails Porphyromonas gingivalis-induced inflammatory responses through maintaining levels of tumor necrosis factor receptor-associated factor (TRAF) 3, thereby suppressing NF-κB signaling. Specifically, SGK1 inhibition significantly enhances production of proinflammatory cytokines, including tumor necrosis factor α, interleukin (IL)-6, IL-1ß, and IL-8 in P. gingivalis-stimulated innate immune cells. The results were confirmed with siRNA and LysM-Cre-mediated SGK1 KO mice. Moreover, SGK1 deletion robustly increased NF-κB activity and c-Jun expression but failed to alter the activation of mitogen-activated protein kinase signaling pathways. Further mechanistic data revealed that SGK1 deletion elevates TRAF2 phosphorylation, leading to TRAF3 degradation in a proteasome-dependent manner. Importantly, siRNA-mediated traf3 silencing or c-Jun overexpression mimics the effect of SGK1 inhibition on P. gingivalis-induced inflammatory cytokines and NF-κB activation. In addition, using a P. gingivalis infection-induced periodontal bone loss model, we found that SGK1 inhibition modulates TRAF3 and c-Jun expression, aggravates inflammatory responses in gingival tissues, and exacerbates alveolar bone loss. Altogether, we demonstrated for the first time that SGK1 acts as a rheostat to limit P. gingivalis-induced inflammatory immune responses and mapped out a novel SGK1-TRAF2/3-c-Jun-NF-κB signaling axis. These findings provide novel insights into the anti-inflammatory molecular mechanisms of SGK1 and suggest novel interventional targets to inflammatory diseases relevant beyond the oral cavity.

Serum- and Glucocorticoid-Inducible Kinase 1 Promotes Alternative Macrophage Polarization and Restrains Inflammation through FoxO1 and STAT3 Signaling.

Expression and activity of serum- and glucocorticoid-inducible kinase 1 (SGK1) are associated with many metabolic and inflammatory diseases. In this study, we report that SGK1 promotes alternative macrophage polarization and restrains inflammation in the infectious milieu of the gingiva. Inhibition of SGK1 expression or activity enhances characteristics of classically activated (M1) macrophages by directly activating the transcription of genes encoding iNOS, IL-12P40, TNF-α, and IL-6 and repressing IL-10 at message and protein levels. Moreover, SGK1 inhibition robustly reduces the expression of alternatively activated (M2) macrophage molecular markers, including arginase-1, Ym-1, Fizz1, and Mgl-1. These results were confirmed by multiple gain- and loss-of-function approaches, including small interfering RNA, a plasmid encoding SGK1, and LysM-Cre-mediated sgk1 gene knockout. Further mechanistic analysis showed that SGK1 deficiency decreases STAT3 but increases FoxO1 expression in macrophages under M2 or M1 macrophage-priming conditions, respectively. Combined with decreased FoxO1 phosphorylation and the subsequent suppressed cytoplasmic translocation observed, SGK1 deficiency robustly enhances FoxO1 activity and drives macrophage to preferential M1 phenotypes. Furthermore, FoxO1 inhibition abrogates M1 phenotypes, and STAT3 overexpression results in a significant increase of M2 phenotypes, indicating that both FoxO1 and STAT3 are involved in SGK1-mediated macrophage polarization. Additionally, SGK1 differentially regulates the expression of M1 and M2 molecular markers, including CD68 and F4/F80 and CD163 and CD206, respectively, and protects against Porphyromonas gingivalis-induced alveolar bone loss in a mouse model. Taken together, these results have demonstrated that SGK1 is critical for macrophage polarization and periodontal bone loss, and for the first time, to our knowledge, we elucidated a bifurcated signaling circuit by which SGK1 promotes alternative, while suppressing inflammatory, macrophage polarization.

A novel polymer enabled by polymerized small molecule strategy for tumor photothermal and photodynamic therapy.

Photothermal therapy (PTT) and photodynamic therapy (PDT) are effective method for tumor treatment. However, the limited variety and quantity of photothermal agents (PTAs) and photosensitizer (PSs) are still major challenges. Moreover, the cell apoptosis mechanism induced by PDT and PTT is still elusive. A fused-ring small molecule acceptor-donor acceptor' donor-acceptor (A-DA'D-A) type of Y5 (Scheme 1) has a narrow band-gap and strong light absorption. Herein, we used Y5 to polymerize with thiophene unit to obtain polymer PYT based on polymerized small molecule strategy, and PYT nanoparticles (PYT NPs) was prepared via one-step nanoprecipitation strategy with DSPE-PEG2000. PYT NPs had excellent biocompatibility, good photostability, high photothermal conversion efficiency (67%) and reactive oxygen species (ROS) production capacity under 808 nm laser irradiation (PYT NPs + NIR). In vitro and in vivo experiments revealed that PYT NPs + NIR had the ability to completely ablate tumor cells. It was demonstrated that cell apoptosis induced by PYT NPs + NIR was closely related to mitochondrial damage. This study provides valuable guidance for constructing high-performance organic PTAs and PSs for tumor treatment. Scheme 1 PYT enabled by polymerized small molecule strategy for tumor photothermal and photodynamic therapy.

Flavonoid-Loaded Biomaterials in Bone Defect Repair.

Skeletons play an important role in the human body, and can form gaps of varying sizes once damaged. Bone defect healing involves a series of complex physiological processes and requires ideal bone defect implants to accelerate bone defect healing. Traditional grafts are often accompanied by issues such as insufficient donors and disease transmission, while some bone defect implants are made of natural and synthetic polymers, which have characteristics such as good porosity, mechanical properties, high drug loading efficiency, biocompatibility and biodegradability. However, their antibacterial, antioxidant, anti-inflammatory and bone repair promoting abilities are limited. Flavonoids are natural compounds with various biological activities, such as antitumor, anti-inflammatory and analgesic. Their good anti-inflammatory, antibacterial and antioxidant activities make them beneficial for the treatment of bone defects. Several researchers have designed different types of flavonoid-loaded polymer implants for bone defects. These implants have good biocompatibility, and they can effectively promote the expression of angiogenesis factors such as VEGF and CD31, promote angiogenesis, regulate signaling pathways such as Wnt, p38, AKT, Erk and increase the levels of osteogenesis-related factors such as Runx-2, OCN, OPN significantly to accelerate the process of bone defect healing. This article reviews the effectiveness and mechanism of biomaterials loaded with flavonoids in the treatment of bone defects. Flavonoid-loaded biomaterials can effectively promote bone defect repair, but we still need to improve the overall performance of flavonoid-loaded bone repair biomaterials to improve the bioavailability of flavonoids and provide more possibilities for bone defect repair.

Effect of Human Periodontal Ligament Stem Cell-Derived Extracellular Vesicles on Macrophage Pyroptosis and Periodontal Inflammatory Injury in Periodontitis.

Periodontitis is an inflammatory disease resulting from subgingival microorganisms. Human periodontal ligament stem cells (hPDLSCs) can be applied in periodontal tissue regeneration. This study investigated the effect of hPDLSC-derived extracellular vesicles (EVs) on periodontitis. hPDLSC-derived EVs were isolated and identified. The murine model of periodontitis was established by ligation, and the cell model of periodontitis was established by treatment of macrophages with lipopolysaccharide (LPS). The effects of EVs on macrophage pyroptosis and periodontal inflammatory injury were measured by the means of HE staining, detection of LDH content, CCK-8 assay, Calcein-AM/PI staining, ELISA, Western blot, as well as measurement of caspase-1, SOD, and MDA. miR-590-3p expression was detected using RT-qPCR. miR-590-3p expression was then intervened to validate the effect of miR-590-3p on macrophage pyroptosis. The binding relationship between miR-590-3p and TLR4 was verified using dual-luciferase assay. Functional rescue experiment was performed to validate the role of TLR4 in macrophage pyroptosis. The results showed that inflammatory levels and macrophage pyroptosis were enhanced in the in vivo and in vitro models of periodontitis, evidenced by the increased NLRP3, GSDMD-N, caspase-1, IL-1ß, IL-18, TNF-α, and MDA and decreased IL-10 and SOD. EVs alleviated periodontal inflammatory injury and macrophage pyroptosis. Physiologically, EVs carried miR-590-3p into macrophages to upregulate miR-590-3p expression and thereby suppress TLR4 transcription. miR-590-3p silencing or TLR4 overexpression reduced the inhibitory effect of EVs on macrophage pyroptosis. Collectively, EVs carried miR-590-3p into macrophages to subsequently inhibit TLR4 transcription, thereby reducing macrophage pyroptosis and alleviating periodontal inflammatory injury.

Glucose oxidase-encapsulated liposomes for amplified autofluorescence-free immunoassay of a prostate-specific antigen with photoluminescence of CePO4:Tb nanocrystals.

Lanthanide-doped inorganic nanocrystals have attracted extensive attention due to their long luminescence lifetime and large Stokes shift. In this work, an immunosensing platform based on CePO4:Tb (CPOT) was successfully constructed, which could avoid the autofluorescence interference of complex biological matrices. Specifically, CPOT was synthesized by a solvothermal method, which exhibited H2O2-responsive luminescence behavior. Taking advantage of this feature, an autofluorescence-free immunosensor with CPOT as the probe and H2O2 as the quencher was developed to detect prostate-specific antigen (PSA). Functionalized liposomes were used to encapsulate glucose oxidase (GOD) and labeled on detection antibodies to improve the sensitivity of the probe. Under the proven optimal experimental conditions, the developed autofluorescence-free immunosensor exhibited a linear luminescence response to the logarithm of PSA concentration (0.005-25 ng mL-1) with a limit of detection (LOD) of 3.25 pg mL-1. The performance shows that the autofluorescence-free immunosensor based on this strategy opens up a new field of vision for clinical PSA detection.

Periodontitis aggravates renal inflammatory response in a mouse model of renal fibrosis.

OBJECTIVES: To assess the effects of periodontitis on renal interstitial fibrosis in a mouse model. MATERIALS AND METHODS: Thirty C57BL/6 male mice were divided into control, periodontitis (PD), unilateral ureteral ligation (UUO) and PD+UUO groups. Unilateral ureteral ligation was performed 6 days after periodontitis. After 2 weeks, all mice were sacrificed, and samples were collected for the assessment of gene expression, immune cells, biochemical indicators and renal pathology. RESULTS: Expression of tumour necrosis factor-α, interleukin-1ß, and Ly6G in the kidneys in the PD+UUO group was significantly greater than in the UUO group. The percentage of CD11b+ Ly6G+ cells was significantly higher in the PD+UUO than in the UUO group. Fibrotic areas in the kidneys in the PD+UUO group were slightly, but not significantly, greater than those in the UUO group. Kidneys from the PD+UUO group showed markedly higher gene expression of matrix metalloproteinase-9, but not α-smooth muscle actin or collagen I, than those in the UUO group. There were no significant differences in blood urea nitrogen, serum creatinine and uric acid between the PD+UUO and UUO groups. CONCLUSIONS: Periodontitis increases the renal inflammatory response without showing a significant influence on renal interstitial fibrosis or renal function in the UUO mouse model.

Biomimetic N-Doped Graphene Membrane for Proton Exchange Membranes.

Proton exchange membranes (PEMs) with both high selectivity and high permeance are of great demand in hydrogen-based applications, especially in fuel cells. Although graphene membranes have shown high selectivity of protons over other ions and molecules, the relatively low permeance of protons through perfect pristine graphene restricts its practical applications. Inspired by the nitrogen-assisted proton transport in biological systems, we introduced N-doping to increase the proton permeance and proposed a type of N-doped graphene membranes (NGMs) for proton exchange, which have both high proton permeance and high selectivity. Compared to the state-of-the-art commercial PEMs, the NGMs show significant increases in both areal proton conductivity (2-3 orders of magnitude) and selectivity of proton to methanol (1-2 orders of magnitude). The work realized the controllable tuning of proton permeance of the graphene membrane with N-doping and developed a new type of graphene-based PEMs with high performance for practical applications.

Recent Advance in Biological Responsive Nanomaterials for Biosensing and Molecular Imaging Application.

In recent decades, as a subclass of biomaterials, biologically sensitive nanoparticles have attracted increased scientific interest. Many of the demands for physiologically responsive nanomaterials in applications involving the human body cannot be met by conventional technologies. Due to the field's importance, considerable effort has been expended, and biologically responsive nanomaterials have achieved remarkable success thus far. This review summarizes the recent advancements in biologically responsive nanomaterials and their applications in biosensing and molecular imaging. The nanomaterials change their structure or increase the chemical reaction ratio in response to specific bio-relevant stimuli (such as pH, redox potentials, enzyme kinds, and concentrations) in order to improve the signal for biologically responsive diagnosis. We use various case studies to illustrate the existing issues and provide a clear sense of direction in this area. Furthermore, the limitations and prospects of these nanomaterials for diagnosis are also discussed.

Research Progress on Synthesis and Application of Cyclodextrin Polymers.

Cyclodextrins (CDs) are a series of cyclic oligosaccharides formed by amylose under the action of CD glucosyltransferase that is produced by Bacillus. After being modified by polymerization, substitution and grafting, high molecular weight cyclodextrin polymers (pCDs) containing multiple CD units can be obtained. pCDs retain the internal hydrophobic-external hydrophilic cavity structure characteristic of CDs, while also possessing the stability of polymer. They are a class of functional polymer materials with strong development potential and have been applied in many fields. This review introduces the research progress of pCDs, including the synthesis of pCDs and their applications in analytical separation science, materials science, and biomedicine.

Clinical efficacy of mineralized collagen (MC) versus anorganic bovine bone (Bio-Oss) for immediate implant placement in esthetic area: a single-center retrospective study.

BACKGROUND: The purpose of this retrospective study was to evaluate the clinical efficacy of mineralized collagen (MC) versus anorganic bovine bone (Bio-Oss) for immediate implant placement in esthetic area. METHODS: Medical records of Department of Oral and Maxillofacial Surgery of Shandong Provincial Hospital were screened for patients who had been treated with immediate implant implantation in the esthetic area using either MC (Allgens®, Beijing Allgens Medical Science and Technology Co., Ltd., China) or Bio-Oss (Bio-Oss®, Geistlich Biomaterials, Wolhusen, Switzerland), between January 2018 and December 2019. All patients fulfilling the in-/exclusion criteria and following followed for a minimum period of 1 year after surgery were enrolled into the presented study. Implant survival rate, radiographic, esthetic and patient satisfactory evaluations were performed. RESULTS: Altogether, 70 patients were included in the study; a total of 80 implants were inserted. All implants had good initial stability. The survival rate of implants was 100% at 1-year follow-up. The differences in horizontal and vertical bone loss between the MC group (0.72 ± 0.26 mm, 1.62 ± 0.84 mm) and the Bio-Oss group (0.70 ± 0.52 mm, 1.57 ± 0.88 mm) were no significant difference statistically no significant 6 months after permanent restoration. Similar results occurred at 12 months after permanent restoration functional loaded. Clinical acceptability defined by pink esthetic score (PES) ≥ 6 (6.07 ± 1.62 vs. 6.13 ± 1.41) was not significantly different between groups. Patient satisfaction estimated by visual analog scale (VAS) was similar (8.56 ± 1.12 vs. 8.27 ± 1.44), and the difference was no significant difference between the two groups. CONCLUSIONS: The biomimetic MC showed a similar behaviour as Bio-Oss not only in its dimensional tissues changes but also in clinical acceptability and patient satisfaction. Within the limitations of this study, these cases show that MC could be considered as an alternative bone graft in IIP.

Catalytic Generation of Nitric Oxide from Poly(ε-caprolactone)/Phosphobetainized Keratin Mats for a Vascular Tissue Engineering Scaffold.

Tissue-engineered vascular graft (TEVG) is a promising alternative to meet the clinical demand of organ shortages. Herein, human hair keratin was extracted by the reduction method, followed by modification with zwitterionic 2-methacryloyloxyethyl phosphorylcholine (MPC) through thiol-Michael addition to improve blood clotting nature. Then, phosphobetainized keratin (PK) was coelectrospun with poly(ε-caprolactone) (PCL) to afford PCL/PK mats with a ratio of 7:3. The surface morphology, chemical structure, and wettability of these mats were characterized. The biocomposite mats selectively enhanced adhesion, migration, and growth of endothelial cells (ECs) while suppressed proliferation of smooth muscle cells (SMCs) in the presence of glutathione (GSH) and GSNO due to the catalytic generation of NO. In addition, these mats exhibited good blood anticoagulant activity by reducing platelet adhesion, prolonging blood clotting time, and inhibiting hemolysis. Taken together, these NO-generating PCL/PK mats have potential applications as a scaffold for vascular tissue engineering with rapid endothelialization and reduced SMC proliferation.

The Structural Characteristics of Seaweed Polysaccharides and Their Application in Gel Drug Delivery Systems.

In recent years, researchers across various fields have shown a keen interest in the exploitation of biocompatible natural polymer materials, especially the development and application of seaweed polysaccharides. Seaweed polysaccharides are a multi-component mixture composed of one or more monosaccharides, which have the functions of being anti-virus, anti-tumor, anti-mutation, anti-radiation and enhancing immunity. These biological activities allow them to be applied in various controllable and sustained anti-inflammatory and anticancer drug delivery systems, such as seaweed polysaccharide-based nanoparticles, microspheres and gels, etc. This review summarizes the advantages of alginic acid, carrageenan and other seaweed polysaccharides, and focuses on their application in gel drug delivery systems (such as nanogels, microgels and hydrogels). In addition, recent literature reports and applications of seaweed polysaccharides are also discussed.

Amplification of Tumor Oxidative Stresses with Liposomal Fenton Catalyst and Glutathione Inhibitor for Enhanced Cancer Chemotherapy and Radiotherapy.

Amplification of intracellular oxidative stress has been found to be an effective strategy to induce cancer cell death. To this end, we prepare a unique type of ultrasmall gallic acid-ferrous (GA-Fe(II)) nanocomplexes as the catalyst of Fenton reaction to enable persistent conversion of H2O2 to highly cytotoxic hydroxyl radicals (•OH). Then, both GA-Fe(II) and l-buthionine sulfoximine (BSO), an inhibitor of glutathione (GSH) synthesis, are coencapsulated within a stealth liposomal nanocarrier. Interestingly, the obtained BSO/GA-Fe(II)@liposome is able to efficiently amplify intracellular oxidative stress via increasing •OH generation and reducing GSH biosynthesis. After chelating with 99mTc4+ radioisotope, such BSO/GA-Fe(II)@liposome could be tracked under in vivo single-photon-emission-computed-tomography (SPECT) imaging, which illustrates the time-dependent tumor homing of such liposomal nanoparticles after intravenous injection. With GA-Fe(II)-mediated •OH production and BSO-mediated GSH depletion, treatment with such BSO/GA-Fe(II)@liposome would lead to dramatically enhanced intratumoral oxidative stresses, which then result in remarkably improved therapeutic efficacies of concurrently applied chemotherapy or radiotherapy. This work thus presents the concise fabrication of biocompatible BSO/GA-Fe(II)@liposome as an effective adjuvant nanomedicine to promote clinically used conventional cancer chemotherapy and radiotherapy, by greatly amplifying the intratumoral oxidative stress.

The miR-3940-5p inhibits cell proliferation of gingival mesenchymal stem cells.

OBJECTIVES: Drug-induced gingival overgrowth (DIGO) is a well-recognized side effect of nifedipine (NIF). However, the molecular mechanisms of DIGO are still unknown. Here, we explored the possible role of miR-3940-5p in DIGO using NIF-treated gingival mesenchymal stem cells (GMSCs). MATERIAL AND METHODS: CFSE and cell cycle assays were used to examine cell proliferation. The alkaline phosphatase (ALP) activity assay, Alizarin Red staining, quantitative calcium analysis, and osteogenesis-related gene expression were used to examine osteo/dentinogenic differentiation. RESULTS: The CFSE assay showed that NIF enhanced cell proliferation, and the over-expression of miR-3940-5p inhibited the proliferation of GMSCs with or without NIF stimulation. Cell cycle assays revealed that the cell cycle was arrested at the G0/G1 phase. Furthermore, it was found that the over-expression of miR-3940-5p upregulated p15INK4b , p18INK4c , p19INK4d , and Cyclin A and downregulated Cyclin E in GMSCs with or without NIF treatment. In addition, the over-expression of miR-3940-5p enhanced ALP activity and mineralization in vitro and increased the expression of the osteo/dentinogenic differentiation markers DSPP and DMP1 and the key transcription factor DLX5 in GMSCs. CONCLUSIONS: miR-3940-5p inhibited cell proliferation, enhanced the osteo/dentinogenic differentiation of GMSCs, and might play a role in DIGO as a potent agent in the treatment of nifedipine-induced gingival overgrowth.

Cellulose Synthase Mutants Distinctively Affect Cell Growth and Cell Wall Integrity for Plant Biomass Production in Arabidopsis.

Cellulose is the most characteristic component of plant cell walls, and plays a central role in plant mechanical strength and morphogenesis. Despite the fact that cellulose synthase (CesA) mutants exhibit a reduction in cellulose level, much remains unknown about their impacts on cell growth (elongation and division) and cell wall integrity that fundamentally determine plant growth. Here, we examined three major types of AtCesA mutants (rsw1, an AtCesA1 mutant; prc1-1 and cesa6, AtCesA6-null mutants; and IRX3, an AtCesA7 mutant) and transgenic mutants that overexpressed AtCesA genes in the background of AtCesA6-null mutants. We found that AtCesA6-null mutants showed a reduced cell elongation of young seedlings with little impact on cell division, which consequently affected cell wall integrity and biomass yield of mature plants. In comparison, rsw1 seedlings exhibited a strong defect in both cell elongation and division at restrictive temperature, whereas the IRX3 mutant showed normal seedling growth. Analyses of transgenic mutants indicated that primary wall AtCesA2, AtCesA3, AtCesA5 and AtCesA9 genes played a partial role in restoration of seedling growth. However, co-overexpression of AtCesA2 and AtCesA5 in AtCesA6-null mutants could greatly enhance cell division and fully restore wall integrity, leading to a significant increase in secondary wall thickness and biomass production in mature plants. Hence, this study has demonstrated distinct functions of AtCesA genes in plant cell growth and cell wall deposition for biomass production, which helps to expalin our recent finding that only three AtCesA6-like genes, rather than other AtCesA genes of the AtCesA family, could greatly enhance biomass production in transgenic Arabidopsis plants.

Red Blood Cells as Smart Delivery Systems.

Red blood cells (RBCs), also called erythrocytes, are the most abundant type of blood cells. Recently, RBCs have been extensively studied as drug delivery systems because of their remarkable properties, including their inherent biocompatibility, low immunogenicity, flexibility, and long systemic circulation. Over the years, a number of different RBC-based drug delivery systems, including genetically engineered RBCs, nongenetically engineered RBCs, and RBC membrane-coated nanoparticles, have been explored, aiming at diverse biomedical applications. These techniques may address many challenging issues faced by traditional drug delivery systems, as demonstrated by the many successful preclinical results. Novel techniques dedicated to producing drug-carrying RBCs are currently undergoing the transition from preclinical research to the clinical realm. In this Topical Review, we will summarize the latest progress in the development of RBC-based smart delivery systems for various biomedical applications.