Comparative analysis of microbial composition and functional characteristics in dental plaque and saliva of oral cancer patients.

BACKGROUND: The oral cavity is home to various ecological niches, each with its own unique microbial composition. Understanding the microbial communities and gene composition in different ecological niches within the oral cavity of oral cancer (OC) patients is crucial for determining how these microbial populations contribute to disease progression. METHODS: In this study, saliva and dental plaque samples were collected from patients with OC. Metagenomic sequencing was employed to analyze the microbial community classification and functional composition of the different sample groups. RESULTS: The results of the study revealed significant differences in both the function and classification of microbial communities between saliva and dental plaque samples. The diversity of microbial species in saliva was found to be higher compared to  that in plaque samples. Notably, Actinobacteria were enriched in the dental plaque of OC patients. Furthermore, the study identified several inter-group differential marker species, including Prevotella intermedia, Haemophilus parahaemolyticus, Actinomyces radius, Corynebacterium matruchitii, and Veillonella atypica. Additionally, 1,353 differential genes were annotated into 23 functional pathways. Interestingly, a significant correlation was observed between differentially labeled species and Herpes simplex virus 1 (HSV-1) infection, which may be related to the occurrence and development of cancer. CONCLUSIONS: Significant differences in the microbial and genetic composition of saliva and dental plaque samples were observed in OC patients. Furthermore, pathogenic bacteria associated with oral diseases were predominantly enriched in saliva. The identification of inter-group differential biomarkers and pathways provide insights into the relationship between oral microbiota and the occurrence and development of OC.

Synthesis of Metallopolymers and Direct Visualization of the Single Polymer Chain.

During the past few decades, the study of the single polymer chain has attracted considerable attention with the goal of exploring the structure-property relationship of polymers. It still, however, remains challenging due to the variability and low atomic resolution of the amorphous single polymer chain. Here, we demonstrated a new strategy to visualize the single metallopolymer chain with a hexameric or trimeric supramolecule as a repeat unit, in which Ru(II) with strong coordination and Fe(II) with weak coordination were combined together in a stepwise manner. With the help of ultrahigh-vacuum, low-temperature scanning tunneling microscopy (UHV-LT-STM) and scanning tunneling spectroscopy (STS), we were able to directly visualize both Ru(II) and Fe(II), which act as staining reagents on the repeat units, thus providing detailed structural information for the single polymer chain. As such, the direct visualization of the single random polymer chain is realized to enhance the characterization of polymers at the single-molecule level.

Zwitterionic Reduction-Activated Supramolecular Prodrug Nanocarriers for Photodynamic Ablation of Cancer Cells.

An adamantane-containing zwitterionic copolymer poly(2-(methacryloyloxy)ethyl phosphorylcholine)- co-poly(2-(methacryloyloxy)ethyl adamantane-1-carboxylate) (poly(MPC- co-MAda)) was prepared by reversible addition-fragmentation chain transfer (RAFT) polymerization. The hydrophobic photosensitizer chlorin e6 (Ce6) was conjugated to ß-cyclodextrin (ß-CD) by glutathione (GSH)-sensitive disulfide bonds. The Ce6 conjugated supramolecular prodrug nanocarriers were fabricated due to the host-guest interaction between adamantane and ß-CD, which was confirmed by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The Ce6 conjugated prodrug nanocarriers showed reduction-responsive release of Ce6, which could result in the activation of Ce6. The generation of cytotoxic reactive oxygen species (ROS) was significantly enhanced due to the activation of Ce6. In additiona, the Ce6 conjugated prodrug nanocarriers could effectively inhibit the proliferation of cancer cells upon light irradiation.

The Use of the Kurtosis-Adjusted Cumulative Noise Exposure Metric in Evaluating the Hearing Loss Risk for Complex Noise.

OBJECTIVE: To test a kurtosis-adjusted cumulative noise exposure (CNE) metric for use in evaluating the risk of hearing loss among workers exposed to industrial noises. Specifically, to evaluate whether the kurtosis-adjusted CNE (1) provides a better association with observed industrial noise-induced hearing loss, and (2) provides a single metric applicable to both complex (non-Gaussian [non-G]) and continuous or steady state (Gaussian [G]) noise exposures for predicting noise-induced hearing loss (dose-response curves). DESIGN: Audiometric and noise exposure data were acquired on a population of screened workers (N = 341) from two steel manufacturing plants located in Zhejiang province and a textile manufacturing plant located in Henan province, China. All the subjects from the two steel manufacturing plants (N = 178) were exposed to complex noise, whereas the subjects from textile manufacturing plant (N = 163) were exposed to a G continuous noise. Each subject was given an otologic examination to determine their pure-tone HTL and had their personal 8-hr equivalent A-weighted noise exposure (LAeq) and full-shift noise kurtosis statistic (which is sensitive to the peaks and temporal characteristics of noise exposures) measured. For each subject, an unadjusted and kurtosis-adjusted CNE index for the years worked was created. Multiple linear regression analysis controlling for age was used to determine the relationship between CNE (unadjusted and kurtosis adjusted) and the mean HTL at 3, 4, and 6 kHz (HTL346) among the complex noise-exposed group. In addition, each subject's HTLs from 0.5 to 8.0 kHz were age and sex adjusted using Annex A (ISO-1999) to determine whether they had adjusted high-frequency noise-induced hearing loss (AHFNIHL), defined as an adjusted HTL shift of 30 dB or greater at 3.0, 4.0, or 6.0 kHz in either ear. Dose-response curves for AHFNIHL were developed separately for workers exposed to G and non-G noise using both unadjusted and adjusted CNE as the exposure matric. RESULTS: Multiple linear regression analysis among complex exposed workers demonstrated that the correlation between HTL3,4,6 and CNE controlling for age was improved when using the kurtosis-adjusted CNE compared with the unadjusted CNE (R = 0.386 versus 0.350) and that noise accounted for a greater proportion of hearing loss. In addition, although dose-response curves for AHFNIHL were distinctly different when using unadjusted CNE, they overlapped when using the kurtosis-adjusted CNE. CONCLUSIONS: For the same exposure level, the prevalence of NIHL is greater in workers exposed to complex noise environments than in workers exposed to a continuous noise. Kurtosis adjustment of CNE improved the correlation with NIHL and provided a single metric for dose-response effects across different types of noise. The kurtosis-adjusted CNE may be a reasonable candidate for use in NIHL risk assessment across a wide variety of noise environments.

Manufacturing and post-engineering strategies of hydrogel actuators and sensors: From materials to interfaces.

Living bodies are made of numerous bio-sensors and actuators for perceiving external stimuli and making movement. Hydrogels have been considered as ideal candidates for manufacturing bio-sensors and actuators because of their excellent biocompatibility, similar mechanical and electrical properties to that of living organs. The key point of manufacturing hydrogel sensors/actuators is that the materials should not only possess excellent mechanical and electrical properties but also form effective interfacial connections with various substrates. Traditional hydrogel normally shows high electrical resistance (~ MΩ•cm) with limited mechanical strength (<1 MPa), and it is prone to fatigue fracture during continuous loading-unloading cycles. Just like iron should be toughened and hardened into steel, manufacturing and post-treatment processes are necessary for modifying hydrogels. Besides, advanced design and manufacturing strategies can build effective interfaces between sensors/actuators and other substrates, thus enhancing the desired mechanical and electrical performances. Although various literatures have reviewed the manufacture or modification of hydrogels, the summary regarding the post-treatment strategies and the creation of effective electrical and mechanically sustainable interfaces are still lacking. This paper aims at providing an overview of the following topics: (i) the manufacturing and post-engineering treatment of hydrogel sensors and actuators; (ii) the processes of creating sensor(actuator)-substrate interfaces; (iii) the development and innovation of hydrogel manufacturing and interface creation. In the first section, the manufacturing processes and the principles for post-engineering treatments are discussed, and some typical examples are also presented. In the second section, the studies of interfaces between hydrogels and various substrates are reviewed. Lastly, we summarize the current manufacturing processes of hydrogels, and provide potential perspectives for hydrogel manufacturing and post-treatment methods.

A Decellularized Matrix Hydrogel Derived from Human Dental Pulp Promotes Dental Pulp Stem Cell Proliferation, Migration, and Induced Multidirectional Differentiation In Vitro.

INTRODUCTION: Dental pulp is a major composition in the pulp-dentin complex, which serves as protective system against dental trauma/infection. Functional dental pulp regeneration is highly desirable after pulpitis or pulp necrosis. However, endodontic regeneration has remained challenging for decades because of the deconstructive microenvironment and the lack of functional cells within the root canal system. The present study developed a decellularized matrix hydrogel derived from human dental pulp (hDDPM-G), which might serve as a growth-permissive microenvironment for dental pulp regeneration. METHODS: Human dental pulps extracted from healthy wisdom teeth were decellularized and digested and then underwent sol-gel transition to form hDDPM-G. The protein compositions were identified by proteomic analysis. Human dental pulp stem cells (hDPSCs) were seeded on hDDPM-G-coated surfaces and evaluated by immunofluorescence staining, transwell migration, and Cell Counting Kit-8 (Dojindo, Kumamoto, Japan) assays. Induced hDPSC differentiation was examined in vitro and characterized by immunostaining, Western blotting, and reverse transcription polymerase chain reaction. RESULTS: Complete decellularization was implemented. Protein contents found in the human decellularized dental pulp matrix were identified to contribute in promoting cell proliferation, migration, and regulation of stem cell differentiation. The hDDPM-G-coated surfaces promoted hDPSC adhesion, migration, and proliferation. Furthermore, hDDPM-G coatings facilitated odontoblastlike, neural-like, and angiogenic differentiation of the seeded hDPSCs after being cultured in induction media for 14 days. CONCLUSIONS: This study showed that hDDPM-G effectively contributed in promoting hDPSC proliferation and migration and induced multidirectional differentiation. Considering the injectability and gelation at body temperature, hDDPM-G may hold translational potential for endodontic regeneration.

Expression of nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 6 in human dental pulp tissues and cells.

OBJECTIVE: This study aims to investigate the expression pattern of nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 6 (NLRP6) in human dental pulp tissues and cells, and roughly explore the role of NLRP6 in dental pulp immunity. METHODS: Immunohistochemistry and immunofluorescence double staining were performed to determine the expression and localization of NLRP6 in healthy and inflamed pulp tissues. The expression of NLRP6 in human dental pulp cells (HDPCs) was investigated by immunocytofluorescence. Furthermore, reverse transcription polymerase chain reaction (RT-PCR) and western blot were used to evaluate the impact of lipopolysaccharide (LPS) stimulation on NLRP6 expression in HDPCs. Last, NLRP6 gene was silenced by lentiviral short hairpin RNA to explore the impact of NLRP6 on LPS-induced interleukin (IL)-1ß. RESULTS: NLRP6 was predominantly expressed in odontoblasts layer and blood vessels of healthy dental pulp, as well as infiltrated immune cells and fibroblasts of inflamed pulp. Further immunofluorescence double staining showed that pericytes and endothelial cells in the dental pulp blood vessels, macrophages and T cells as well as fibroblasts in the inflamed pulp expressed NLRP6. NLRP6 was also basically expressed in cultured HDPCs and upregulated by LPS stimulation. Knockdown of NLRP6 in HDPCs significantly inhibited the LPS-induced IL-1ß expression. CONCLUSIONS: Our study revealed the expression and distribution of NLRP6 in human dental pulp tissues. Furthermore, NLRP6 was also basically expressed in cultured HDPCs, which could be upregulated by LPS stimulation, indicating the involvement of NLRP6 in dental pulp immune response.

Exosomes Secreted by Stem Cells from Human Exfoliated Deciduous Teeth Promote Alveolar Bone Defect Repair through the Regulation of Angiogenesis and Osteogenesis.

Exosomes are important mediators of intercellular communication and have a vital part in the diagnosis and treatment of various diseases in humans. Here, we investigated the benefits and underlying mechanism of exosomes secreted via stem cells from human exfoliated deciduous teeth (SHED-derived exosomes) in promoting alveolar bone regeneration, thus providing new insights into exosome-based therapy for periodontitis. SHED-derived exosomes were isolated by ultracentrifugation. The impacts of SHED-derived exosomes on the angiogenic ability of human umbilical vein endothelial cells (HUVECs) and the osteogenic capability of rat bone marrow mesenchymal stem cells (BMSCs) were evaluated in vitro. Compound C, a pharmacological blocker of adenosine monophosphate-activated protein kinase (AMPK), was used to examine the role of the AMPK signaling cascade in these processes. Periodontal defect rat models were established and treated with PBS, ß-tricalcium phosphate (ß-TCP), or a grouping of exosomes/ß-TCP. Microcomputed tomography (micro-CT) scanning, hematoxylin and eosin (HE) staining, Masson staining, and immunofluorescence staining were done to inspect the impacts of the exosomes/ß-TCP combination on periodontal bone regeneration. Our outcomes indicated that the expression of angiogenesis-related genes (KDR, SDF-1, and FGF2), osteogenesis-related genes (COL1, RUNX2, and OPN), and phosphorylated (p)-AMPK were upregulated after treatment with exosomes, while the positive impacts of SHED-derived exosomes on HUVECs and BMSCs were partially reversed by compound C. Micro-CT analysis demonstrated that the exosomes/ß-TCP group exhibited better bone regeneration than either the ß-TCP group or the control group. Additionally, the results of HE and Masson staining as well as immunofluorescence staining showed neovascularization and new bone formation in the exosomes/ß-TCP group but only limited new bone formation in the other two groups. Thus, SHED-derived exosomes contribute to periodontal bone regeneration by promoting neovascularization and new bone formation, possibly through the AMPK signaling pathway.

Assessment of personal noise exposure of overhead-traveling crane drivers in steel-rolling mills.

BACKGROUND: Noise is widespread occupational hazard in iron and steel industry. Overhead-traveling cranes are widely used in this industry, but few studies characterized the overhead-traveling crane drivers' noise exposure level so far. In this study, we assessed and characterized personal noise exposure levels of overhead-traveling crane drivers in two steel-rolling mills. METHODS: One hundred and twenty-four overhead-traveling crane drivers, 76 in the cold steel-rolling mill and 48 in the hot steel-rolling mill, were enrolled in the study. Personal noise dosimeters (AIHUA Instruments Model AWA5610e, Hangzhou, China) were used to collect full-shift noise exposure data from all the participants. Crane drivers carried dosimeters with microphones placed near their collars during the work shifts. Work logs had been taken by the drivers simultaneously. Personal noise exposure data were divided into segments based on lines in which they worked. All statistical analyses were done using SPSS 13.0. RESULTS: The average personal noise exposure (L(Aeq.8h)) of overhead-traveling crane drivers in the hot steel-rolling mills ((85.03 +/- 2.25) dB (A)) was higher than that in the cold one ((83.05 +/- 2.93) dB (A), P < 0.001). There were 17 overhead traveling cranes in the hot steel-rolling mill and 24 cranes in the cold one, of which carrying capacities varied from 15 tons to 100 tons. The average noise exposure level based on different lines in the hot and cold steel-rolling mills were (85.2 +/- 2.61) dB (A) and (83.3 +/- 3.10) dB (A) respectively (P = 0.001), which were similar to the average personal noise exposure in both mills. The noise exposure levels were different among different lines (P = 0.021). CONCLUSION: Noise exposure levels, depending upon background noise levels and the noise levels on the ground, are inconstant. As the noise exposure levels are above the 85 dB (A) criteria, these drivers should be involved in the Hearing Conservation Program to protect their hearing.

A systematic comparison of clinically viable nanomedicines targeting HMG-CoA reductase in inflammatory atherosclerosis.

Atherosclerosis is a leading cause of worldwide morbidity and mortality whose management could benefit from novel targeted therapeutics. Nanoparticles are emerging as targeted drug delivery systems in chronic inflammatory disorders. To optimally exploit nanomedicines, understanding their biological behavior is crucial for further development of clinically relevant and efficacious nanotherapeutics intended to reduce plaque inflammation. Here, three clinically relevant nanomedicines, i.e., high-density lipoprotein ([S]-HDL), polymeric micelles ([S]-PM), and liposomes ([S]-LIP), that are loaded with the HMG-CoA reductase inhibitor simvastatin [S], were evaluated in the apolipoprotein E-deficient (Apoe-/-) mouse model of atherosclerosis. We systematically employed quantitative techniques, including in vivo positron emission tomography imaging, gamma counting, and flow cytometry to evaluate the biodistribution, nanomedicines' uptake by plaque-associated macrophages/monocytes, and their efficacy to reduce macrophage burden in atherosclerotic plaques. The three formulations demonstrated distinct biological behavior in Apoe-/- mice. While [S]-PM and [S]-LIP possessed longer circulation half-lives, the three platforms accumulated to similar levels in atherosclerotic plaques. Moreover, [S]-HDL and [S]-PM showed higher uptake by plaque macrophages in comparison to [S]-LIP, while [S]-PM demonstrated the highest uptake by Ly6Chigh monocytes. Among the three formulations, [S]-PM displayed the highest efficacy in reducing macrophage burden in advanced atherosclerotic plaques. In conclusion, our data demonstrate that [S]-PM is a promising targeted drug delivery system, which can be advanced for the treatment of atherosclerosis and other inflammatory disorders in the clinical settings. Our results also emphasize the importance of a thorough understanding of nanomedicines' biological performance, ranging from the whole body to the target cells, as well drug retention in the nanoparticles. Such systematic investigations would allow rational applications of nanomaterials', beyond cancer, facilitating the expansion of the nanomedicine horizon.

Nanoreporter PET predicts the efficacy of anti-cancer nanotherapy.

The application of nanoparticle drug formulations, such as nanoliposomal doxorubicin (Doxil), is increasingly integrated in clinical cancer care. Despite nanomedicine's remarkable potential and growth over the last three decades, its clinical benefits for cancer patients vary. Here we report a non-invasive quantitative positron emission tomography (PET) nanoreporter technology that is predictive of therapeutic outcome in individual subjects. In a breast cancer mouse model, we demonstrate that co-injecting Doxil and a Zirconium-89 nanoreporter ((89)Zr-NRep) allows precise doxorubicin (DOX) quantification. Importantly, (89)Zr-NRep uptake also correlates with other types of nanoparticles' tumour accumulation. (89)Zr-NRep PET imaging reveals remarkable accumulation heterogeneity independent of tumour size. We subsequently demonstrate that mice with >25 mg kg(-1) DOX accumulation in tumours had significantly better growth inhibition and enhanced survival. This non-invasive imaging tool may be developed into a robust inclusion criterion for patients amenable to nanotherapy.

Engineering of lipid-coated PLGA nanoparticles with a tunable payload of diagnostically active nanocrystals for medical imaging.

Polylactic-co-glycolic acid (PLGA) based nanoparticles are biocompatible and biodegradable and therefore have been extensively investigated as therapeutic carriers. Here, we engineered diagnostically active PLGA nanoparticles that incorporate high payloads of nanocrystals into their core for tunable bioimaging features. We accomplished this through esterification reactions of PLGA to generate polymers modified with nanocrystals. The PLGA nanoparticles formed from modified PLGA polymers that were functionalized with either gold nanocrystals or quantum dots exhibited favorable features for computed tomography and optical imaging, respectively.