Polystyrene exacerbates cadmium-induced mitochondrial damage to lung by blocking autophagy in mice.

Cadmium (Cd) is an environmental heavy metal, and its accumulation is harmful to animal and human health. The cytotoxicity of Cd includes oxidative stress, apoptosis, and mitochondrial histopathological changes. Furthermore, polystyrene (PS) is a kind of microplastic piece derived from biotic and abiotic weathering courses, and has toxicity in various aspects. However, the potential mechanism of action of Cd co-treated with PS is still poorly unclear. The objective of this study was to investigate the effects of PS on Cd-induced histopathological injury of mitochondria in the lung of mice. In this study, the results have showed that Cd could induce the activity of oxidative enzymes of the lung cells in mice, increasing the content of partial microelement and the phosphorylation of inflammatory factor NF-κB p65. Cd further destroys the integrity of mitochondria by increasing the expression of apoptotic protein and blocking the autophagy. In addition, PS solely group aggravated the lung damage in mice, especially mitochondrial toxicity, and played a synergistic effect with Cd in lung injury. However, how PS can augment mitochondrial damage and synergism with Cd in lung of mice requiring further exploration. Therefore, PS was able to exacerbate Cd-induced mitochondrial damage to the lung in mice by blocking autophagy, and was associated with the apoptosis.

Hybrid Hydrogels from Nongelling Polymers Using a Fibrous Peptide Hydrogelator at Low Concentrations.

Nature-made hydrogels typically combine a wide range of multiscale fibers into biological composite networks, which offer an adaptive property. Inspired by nature, we report a facile approach to construct hybrid hydrogels from a range of natural or commercially available synthetic nongelling polymers (e.g., poly(ethylene glycol), poly(acrylic acid), carboxylated cellulose nanocrystal, and sodium alginate) at a concentration as low as 0.53 wt % using a nonionic fibrous peptide hydrogelator. Through simply mixing the peptide hydrogelator with a polymer aqueous solution, stable hybrid hydrogels can be formed with the concentration of hydrogelator at ∼0.05 wt %. The gel strength of the resulting hydrogels can be effectively modulated by the concentration, molecular weight, and terminal group of the polymer. We further demonstrate that the molecular interactions between the peptide hydrogelator and the polymer are very crucial for the formation of hybrid hydrogel, which synergically induce the gelation at considerably low concentrations. A peptide hydrogelator can be easily obtained by aminolysis of alkyl-oilgo(γ-benzyl-l-glutamate) samples. Live/Dead assays indicate low cytotoxicity of the hybrid hydrogel toward HeLa cells. Combining the low-cost, scalable synthesis, and biocompatibility, the prepared peptide hydrogelator presents a potential candidate to expand the scope of polymer hydrogels for biomedical applications and also shows considerable commercial significance.

Tunable Aggregation-Induced Emission Fluorophore with the Assistance of the Self-Assembly of Block Copolymers by Controlling the Morphology and Secondary Conformation for Bioimaging.

Aggregation-induced emission (AIE) luminogens with highly tunable properties show great potential for many applications. In this study, we synthesized a new family of AIE-type poly(ethylene glycol)-block-poly(9-anthrylmethyl lysine) (PEG-b-PLys-An) diblock copolymers by taking advantage of amphiphilic self-assembly and rigid helical backbones. These copolymers can self-assemble into various assemblies through nanoprecipitation methods. The micelles using N,N-dimethylformamide (DMF) as a cosolvent present brighter fluorescence than the vesicles prepared from tetrahydrofuran (THF). We demonstrate that the decreased solubility of copolymers in DMF results in the formation of more compact micelles with more excimer formation during the self-assembly process, while better solvent THF favors the formation of vesicles with stretched core chains. In addition, the secondary conformation of the polypeptide block shows pronounced effects on the fluorescence property. We further show the internalization of the assemblies using two types of cells by cellular uptake experiments. By the delicate design of the block copolymer, we successfully prepare the morphology- and conformation-dependent AIE materials for potential biomedical applications.

Tunable LCST/UCST-Type Polypeptoids and Their Structure-Property Relationship.

Bioinspired thermoresponsive polymeric materials with tunable phase-transition behaviors are highly desirable for biomedical applications. Here, we reported a facile approach for the synthesis of both lower critical solution temperature (LCST) and upper critical solution temperature (UCST) types of thermoresponsive polypeptoids with tunable phase-transition temperature in the range of 29--55 °C. The introduction of alkyl groups and ethylene glycol (EG) units results in a controlled phase-transition behavior under fairly mild conditions. A very sharp transition (ΔT ≤ 1.5 °C) is observed by simply adjusting pH and the alkyl chain length. In particular, the carboxyl-containing polypeptoids display designable UCST behavior, which can be finely tuned in both water and methanol. All these features make the obtained polymers beneficial for practical applications. More interestingly, we demonstrate that the hydrophilic EG group behaves as an excellent regulator to tune the UCST behavior, while the hydrophobic alkyl residues show remarkable capability to regulate the LCST behavior of the system. We hope that such systematic structure-property studies will enable the design of smart polymer materials to meet the specific needs of future applications.

Autotransplantation of third molars with completely formed roots to replace compromised molars with the computer-aided rapid prototyping.

OBJECTIVE: To describe a method to fabricate donor tooth replica to assist surgeons in preparation of recipient socket during tooth autotransplantation. MATERIALS AND METHODS: A total of 28 compromised molars in 27 patients were transplanted with third molars using computer-aided rapid prototyping (CARP) technique. Surgery time and extra-alveolar time were documented. Postoperatively, the distance between cervix of transplanted tooth and the alveolar wall was measured. The degree of postoperative pain experienced was assessed with visual analog scale at day 1, 3, and 7. RESULTS: From 28 clinical cases, the average extra-alveolar time and surgery time were 2.5 minutes (±1.3) and 44 minutes (±6.8), respectively. Postoperatively, the average distance between cervix of transplanted tooth and the alveolar wall was 0.87 mm (±0.15) at the mesial-cervix, 0.95 mm (±0.17) at the distal-cervix, 0.88 mm (±0.18) at the buccal-cervix, and 0.95 mm (±0.13) at the lingual-cervix. The value of visual analog scale score significantly decreased from day 1 to day 3. CONCLUSIONS: CARP is a reliable technique for fabrication of tooth like surgical replicas in conventional autotransplantation. CLINICAL SIGNIFICANCE: CARP technique minimized extra-oral time, reduced iatrogenic damage, and consequently increased the survival rate of tooth autotransplantation.

Dual-responsive pegylated polypeptoids with tunable cloud point temperatures.

A series of pegylated polypeptoids have been readily synthesized by a strategy combining ring-opening polymerization (ROP) and thiol-yne photoaddition. The polypeptoids simultaneously incorporated branched oligo(ethylene glycol) (OEG) units and thioether bonds in the side-chains. All the polypeptoids are readily soluble in aqueous solution and show reversible thermo-responsive properties. The cloud points (CPs) were demonstrated to be readily tunable in the range of ~25°C-60°C by varying the chemical composition, OEG chain length and the degree of polymerization. Attractively, the chemical compositions of the side chains are readily tunable via adjusting the molar ratios of a mixture of thiol terminated OEG molecules, which avoid synthesizing new monomers or copolymerization of different monomers. Further, the oxidation/reduction of thioether groups shows significant influence on the CPs, providing a second stimulus to tune the phase transition behaviors. Considering the biocompatibility and degradability, the dual-responsive polypeptoids are potential candidates for various biomedical or biotechnological applications.

Two-Dimensional Supramolecular Assemblies from pH-Responsive Poly(ethyl glycol)-b-poly(l-glutamic acid)-b-poly(N-octylglycine) Triblock Copolymer.

Amphiphilic block copolymers containing polypeptides can self-assemble into a variety of nonspherical structures arising from strong interactions between peptide units. Here, we report the synthesis of a pH-responsive poly(ethyl glycol)-block-poly(l-glutamic acid)-block-poly(N-octylglycine) (PEG-b-PGA-b-PNOG) triblock copolymers by sequential ring-opening polymerization using amine-terminated poly(ethyl glycol) as the macroinitiator followed by selective deprotection of the benzyl protecting group. The obtained triblock copolymer can be directly dispersed in aqueous solution with hydrophilic PEG, pH-responsive PGA block, and hydrophobic PNOG. We present a systematic study of the influence of pH, molar fraction, and molecular weight on the self-assemblies. It was found that the PEG-b-PGA-b-PNOG triblock tends to form two-dimensional nanodisks and nanosheet-like assemblies. The nanodisk-to-nanosheet transition is highly dependent on the pH and molar fraction despite the different molecular weights. We demonstrate that the dominant driving force of the nanodisks and nanosheets is the hydrophobicity of the PNOG blocks. The obtained bioinspired 2D nanostructures are potential candidates for applications in nanoscience and biomedicine.

Biodegradable stimuli-responsive polypeptide materials prepared by ring opening polymerization.

The stimuli-responsive polypeptides have drawn extensive attention because of their promising applications in biotechnology considering their biocompatibility, biodegradability, and bioactivity. In this tutorial review, we summarize the most recent progress in this area, including thermo-, redox-, photo-, and biomolecule responsive polypeptides over the past decade. The design and synthesis of stimuli-responsive polypeptides will be briefly introduced. The correlation between the structure and properties, particularly the effects of polypeptide conformation, will be emphasized here. In addition, the applications of stimuli-responsive polypeptides in controlled drug release and tissue engineering are briefly discussed.

Oxidation-responsive OEGylated poly-L-cysteine and solution properties studies.

The oxidation-responsive behaviors of OEGylated poly-L-cysteine homopolypeptides, that is, poly(L-EG(x)MA-C)n, were investigated. These poly-L-cysteine derivatives adopted mixed conformation in water, in which the ß-sheet accounted for a significant proportion. Upon oxidation, the thioethers in polypeptide side chains were converted to polar sulfone groups, which triggered the secondary structure transition from ß-sheet preferred conformation to random coil. Accordingly, the increase of side-chain polarity together with conformation changes increased samples' water solubility and cloud point temperature. Using mPEG45-NH2 as macroinitiator, we synthesized PEG45-b-poly(L-EG2MA-C)22 diblock copolymer via ring-opening polymerization (ROP) of L-EG2MA-C N-carboxyanhydride (NCA). The PEG45-b-poly(L-EG2MA-C)22 was able to self-assemble into spherical micelles in aqueous solution, and the micelles could undergo an oxidation-triggered disassembly due to the oxidation-responsive thioethers. Such a new class of oxidation-responsive polypeptides might provide a promising platform to construct inflammation targeting drug delivery systems.

Case report: A novel splice-site mutation of MTX2 gene caused mandibuloacral dysplasia progeroid syndrome: the first report from China and literature review.

Background: Mandibuloacral dysplasia (MAD) syndrome is a rare genetic disease. Several progeroid syndromes including mandibuloacral dysplasia type A (MADA), mandibuloacral dysplasia type B(MADB), Hutchinson-Gilford progeria (HGPS) and mandibular hypoplasia, deafness, and lipodystrophy syndrome (MDPL) have been reported previously. A novel MAD progeroid syndrome (MADaM) has recently been reported. So far, 7 cases of MADaM diagnosed with molecular diagnostics have been reported in worldwide. In the Chinese population, cases of MAD associated with the MTX2 variant have never been reported. Methods: The clinical symptoms and the genetic analysis were identified and investigated in patients presented with the disease. In addition, we analyzed and compared 7 MADaM cases reported worldwide and summarized the progeroid syndromes reported in the Chinese population to date. Results: The present study reports a case of a novel homozygous mutation c.378 + 1G > A in the MTX2 gene, which has not been previously reported in the literature. Patients present with early onset and severe symptoms and soon after birth are found to have growth retardation. In addition to the progeroid features, skeletal deformities, generalized lipodystrophy reported previously, and other multisystem involvement, e.g. hepatosplenic, renal, and cardiovascular system, this case was also reported to have combined hypogammaglobulinemia. She has since been admitted to the hospital several times for infections. Among 22 previously reported progeroid syndromes, 16/22 were MADA or HGPS caused by LMNA gene mutations, and the homozygous c.1579C > T (p.R527C) mutation may be a hot spot mutation for MAD in the Chinese population. MAD and HGPS mostly present in infancy with skin abnormalities or alopecia, MDPL mostly presents in school age with growth retardation as the first manifestation, and is often combined with an endocrine metabolism disorder after several decades. Conclusion: This is the first case of MAD syndrome caused by mutations in MTX2 gene reported in the Chinese population. MTX2 gene c.378 + 1G > A homozygous mutation has not been previously reported and the report of this patient expands the spectrum of MTX2 mutations. In addition, we summarized the genotypes and clinical characteristics of patients with progeroid syndromes in China.

Taxifolin Protects Dental Pulp Stem Cells under Hypoxia and Inflammation Conditions.

BACKGROUND: Dental pulp stem cells (DPSCs) are a unique source for future clinical application in dentistry such as periodontology or endodontics. However, DPSCs are prone to apoptosis under abnormal conditions. Taxifolin is a natural flavonoid and possesses many pharmacological activities including anti-hypoxic and anti-inflammatory. We aimed to elucidate the mechanisms of taxifolin protects DPSC under hypoxia and inflammatory conditions. METHODS: DPSCs from human dental pulp tissue was purchased from Lonza (cat. no. PT-5025. Basel, Switzerland)) and identified by DPSC's biomarkers. DPSC differentiation in vitro following the manufacturers' instructions. ARS staining and Oil red staining verify the efficiency of differentiation in vitro after 2 weeks. The changes of various genes and proteins were identified by Q-PCR and western-blot, respectively. Cell viability was determined by the CCK-8 method, while apoptosis was determined by Annexin V/PI staining. RESULTS: DPSC differentiation in vitro shows that hypoxia and TNF-α synergistically inhibit the survival and osteogenesis of DPSCs. A final concentration of 10 µM Taxifolin can significantly reduce the apoptosis of DPSCs under inflammation and hypoxia conditions. Taxifolin substantially increases carbonic anhydrase IX (CA9) expression but not HIF1a, and inhibitions of CA9 expression nullify the protective role of taxifolin under hypoxia and inflammatory condition. CONCLUSION: Taxifolin significantly increased the expression of CA9 when it inhibits DPSC apoptosis and taxifolin synergistically to protect DPSCs against apoptosis with CA9 under hypoxia and inflammatory conditions. Taxifolin can be used as a potential drug for clinical treatment of DPSC-related diseases.

Possible aerosol transmission of COVID-19 and special precautions in dentistry.

Since its emergence in December 2019, corona virus disease 2019 (COVID-19) has impacted several countries, affecting more than 90 thousand patients and making it a global public threat. The routes of transmission are direct contact, and droplet and possible aerosol transmissions. Due to the unique nature of dentistry, most dental procedures generate significant amounts of droplets and aerosols, posing potential risks of infection transmission. Understanding the significance of aerosol transmission and its implications in dentistry can facilitate the identification and correction of negligence in daily dental practice. In addition to the standard precautions, some special precautions that should be implemented during an outbreak have been raised in this review.

Stromal cell-derived factor 1 protects human periodontal ligament stem cells against hydrogen peroxide-induced apoptosis.

Periodontal ligament stem cells (PDLSCs) are considered a promising cell source for dental tissue regeneration. Stromal cell-derived factor 1 [SDF­1, also known as chemokine (C­X­C motif) ligand 12] is regarded as a critical cytokine involved in stem/progenitor cell chemotaxis and homing during tissue regeneration. The present study described a previously unsuspected role for SDF­1 in the protection of PDLSCs against oxidative stress­induced apoptosis. In the present study, apoptosis was induced by exposure of PDLSCs to various concentrations of H2O2 for 12 h, following which cell viability was assessed, and cleaved caspase­3 and ­9 expression levels were evaluated. To investigate the potential mechanism underlying this protection, the protein expression levels of total and phosphorylated extracellular signal­regulated kinase (ERK), a key protein of the mitogen­activated protein kinase (MAPK) signaling pathway, were examined. The results of the present study revealed that SDF­1 pretreatment increased cell viability following H2O2 administration, and downregulated protein expression levels of activated caspase­3 and ­9. Furthermore, treatment with SDF­1 increased the phosphorylation of ERK. The protective effect of SDF­1 was partially inhibited by treatment with PD98059, a MAPK/ERK inhibitor, which decreased cell viability. The results of the present study suggested that SDF­1 treatment is a potential strategy to improve the survival of PDLSCs, which may be beneficial for dental tissue regeneration.

[Application of distraction osteogenesis in the treatment of severe mandibular micrognathia with severe obstructive sleep apnea and hypopnea syndrome].

OBJECTIVE: To investigate the effect of distraction osteogenesis (DO) in the treatment of severe mandibular micrognathia with severe obstructive sleep apnea and hypopnea syndrome (OSAHS). METHODS: 19 cases of severe mandibular micrognathia with OSAHS were treated by DO. All the patients received PSG and MSCT examination before and after DO to evaluate the therapeutic effect and changes in the upper airway. RESULTS: According to the evaluation standard, 17 cases were cured and 2 cases improved markedly. The sagittal distance and area, transverse distance and area of the upper airway increased markedly after DO. The volume of upper airway increased from (15 572.03 +/- 3 370.11) mm3 to (21 182.69 +/- 4 533.15) mm3.The airway change happened mainly in velopharyngeal region and the lingopharyngeal region, but not in the laryngopharyngeal region. CONCLUSIONS: DO can treat severe mandibular micrognathia patients with OSAHS effectively by enlarging the volume of upper airway,especially in the velopharynx and glossopharyngeum region. The MSCT plays an effective and important role.

[Computer-aided design in double-step distraction osteogenesis of unilateral mandibular segmental defects reconstruction].

OBJECTIVE: To investigate the feasibility of using computer-aided design (CAD) in double-step distraction osteogenesis in the reconstruction of mandibular segmental defects after tumor resection. METHODS: Eight cases of unilateral mandibular segmental defects were reconstructed using distraction osteogenesis secondary to oncologic surgery, with the help of CT and CAD system. The mandibular body was lengthened first, and then the residual defect of mandibular ramus was restored using a distraction device. RESULTS: No incidence of infection or other complications were observed. The maximal amount of the lengthening reached 55 mm in the mandibular body, and 45 mm in the mandibular ramus. The average amount of the lengthening reached 49 mm in the mandibular body, and 36 mm in the mandibular ramus. The aesthetic and functional results of bone lengthening were excellent in all cases. The retractor was removed eight months postoperatively. CONCLUSIONS: Using CAD in double-step distraction osteogenesis in the reconstruction of unilateral mandibular segmental defects has the advantages of precise diagnosis, operation planning and assuring success of operation. It has the disadvantage of a long period for the overall treatment time.

[Soft tissue profile changes in micrognathia after distraction osteogenesis].

OBJECTIVE: To evaluate the effect of distraction osteogenesis for severe micrognathia by comparing the pre- and post-operative profile and mentolabial relationship. METHODS: 16 cases underwent temporal-mandibular joint plasty and temporal fasciomuscular flap transfer. The mandibular distraction began at the 5th postoperative day at a rate of 0.8 mm a day, two times a day. Bony and soft tissue cephalometry were performed before and after operation. T-test was used to study the change after distraction osteogenesis. RESULTS: There were significant differences in facial convexity, lower facial height, lower lip length, inter-labial distance, the ratio of lip to mental, the distance from lip to esthetic plane, the depth of mentolabial crease and the thickness of mental soft tissue. CONCLUSIONS: Mandibular distraction osteogenesis can markedly improve the soft tissue profile of the middle and lower face for severe micrognathia.