Orthodontic maxillary molar movement-induced zygomatic pillar remodeling and its consequences on occlusal characteristics and stress distribution.

OBJECTIVE: We aimed to evaluate changes in the zygomatic pillar during orthodontic treatment involving premolar extraction, analyze the effects of maxillary first molar movement on zygomatic pillar remodeling, and examine occlusal characteristics and stress distribution after remodeling. METHODS: Twenty-five patients who underwent premolar extraction were included in the study. The zygomatic pillar measurement range was defined, and cross-sectional areas, surface landmark coordinates, alveolar and cortical bone thicknesses, and density changes were assessed using Mimics software based on the cone-beam computed tomography scans taken before (T0) and after the treatment (T1). Multiple linear regression analysis was performed to determine the correlation between changes in the zygomatic pillar and maxillary first molar three-dimensional (3D) movement and rotation. Additionally, the correlation between pillar remodeling and occlusal characteristics was analyzed by Teetester. Pre- and post-reconstruction 3D finite element models were constructed and loaded with an average occlusal force of two periods. RESULTS: The morphological and structural remodeling of the zygomatic pillar after orthodontic treatment involving premolar extraction showed a decreased cross-sectional area of the lower segment of the zygomatic pillar. The zygomatic process point moved inward and backward, whereas the zygomatico-maxillary suture point moved backward. The thicknesses of the zygomatic pillar alveolar and cortical bones were thinner, and reduced alveolar bone density was observed. Simultaneously, the movement and angle change of the maxillary first molar could predict zygomatic pillar reconstruction to a certain extent. With decreasing the total occlusal force and the occlusal force of the first molar, occlusal force distribution was more uniform. With zygomatic pillar remodeling, occlusal stress distribution in the zygomatic alveolar ridge decreased, and occlusal stress was concentrated at the junction of the vertical and horizontal parts of the zygomatic bone and the posterior part of the zygomatic arch. CONCLUSIONS: Orthodontic treatment involving premolar extraction led to zygomatic pillar remodeling, making it more fragile than before and reducing the occlusal force of the maxillary first molar and the entire dentition with stress concentrated in weak areas. CLINICAL RELEVANCE: No other study has focused on the effects of orthodontics on pillar structures. The present study indicates that the mesial movement of the maxillary first molar weakened the zygomatic pillar and reduced occlusal function, thereby providing insights for inserting anchorage screws and facial esthetics.

Cerium oxide nanoparticles protect against chondrocytes and cartilage explants from oxidative stress via Nrf2/HO-1 pathway in temporomandibular joint osteoarthritis.

Oxidative stress is closely linked to the etiology of temporomandibular joint osteoarthritis. (TMJ-OA) and is an important therapeutic target. Cerium oxide nanoparticles (CNPs) have been broadly studied owing to their powerful antioxidant properties and potential preventive and therapeutic effects against chronic diseases. The current study was designed to explore the protective effects of CNPs on the progression of TMJ-OA and their potential mechanisms. We detected the ability of CNPs to eliminate reactive oxygen species (ROS) in chondrocytes. Moreover, their protective effects on chondrocytes were detected in the level of gene and protein. Furthermore, TUNEL assay, histology and safranin O-fast green staining were used to detect the beneficial effects of CNPs on cartilage explants. The mechanism of CNPs, protecting condylar cartilage by reducing inflammation, was further explored by knocking down the Nuclear factor-erythroid 2-related factor (Nrf2) gene. CNPs could reduce the ROS levels in chondrocytes and cartilage explants and reverse the IL-1ß-induced imbalance of cartilage matrix metabolism and apoptosis. The protective effects of CNPs on cartilage were lost after key antioxidant factors including Nrf2 and heme-oxygenase 1(HO-1) were significantly reduced. In conclusion, this study demonstrated for the first time that activating the Nrf2/HO-1 signaling pathway by CNPs might have therapeutic potential for TMJ-OA.

Estimation of gingival crevicular fluid oxidative stress markers in school-aged children and teenagers with insufficient sleep.

BACKGROUND: Sleep is crucial for survival. Sleep deprivation causes ROS accumulation and, consequently, oxidative stress. The goal of the study was to evaluate gingival crevicular fluid (GCF) levels of the oxidative stress status hydrogen peroxide (H2O2), superoxide glutathione (GSH), and cellular oxidative damage marker malondialdehyde (MDA) in school-aged children and teenagers with insufficient sleep. METHODS: This study investigated sleep duration in 80 participants from two different developmental stages: school-aged children (6-13 years) and teenagers (14-17 years). GCF samples were obtained from all individuals, and samples were investigated to detect H2O2, GSH, and MDA levels using the micro method. RESULTS: Results reveal that GCF MDA and H2O2 in school-age children and teenagers with insufficient sleep were significantly higher than in children with sufficient sleep. GCF GSH with insufficient sleep was insignificantly lower than in children with sufficient sleep. There was no significant difference between school-age and teenage populations. CONCLUSION: Sleep deprivation causes increased levels of oxidative stress in gingival crevicular fluid, and adequate sleep is essential for maintaining redox balance.

A deep tumor penetration nanoplatform for glycolysis inhibition and antimetastasis of breast cancer.

The poor penetration into deep tumor tissues of nanomedicines could not inhibit the production of lactic acid by deep tumor glycolysis, which leads to the accumulation of lactic acid and promotes tumor metastasis. In order to increase tumor penetration, it remains challenging to avoid tumor metastasis by the direct degradation of the extracellular matrix (ECM). Herein, in order to increase tumor penetration, a nano-platform, which can reduce extracellular matrix (ECM) production, and inhibit the glycolysis of deep tumors by releasing ethylenediaminetetraacetic acid (EDTA) is reported. In this design, EDTA and indocyanine green (ICG) are encapsulated in the liposome by a thin-film hydration method, and folic acid (FA) and the polyethyleneimine polymer (FA-PEI) are applied to coat the surface of liposomes through electrostatic interactions, and the FA-EDTA/ICG-Lip nanoparticles are obtained. FA-EDTA/ICG-Lip NPs can release EDTA and ICG in lysosomes (pH 4.5) to reduce ECM production by down-regulating transforming growth factor ß (TGF-ß) and activating an immune response by inducing tumor cell immunogenic cell death (ICD), respectively. Simultaneously, EDTA inhibits glycolysis of deep tumors by chelating Mg2+. By avoiding tumor metastasis, the strategy of indirectly reducing ECM production is demonstrated to enhance tumor penetration and inhibit deep tumor glycolysis.

A nano-detection system based on a chemical probe for early diagnosis of atherosclerosis in situ.

With the existing medical diagnostic technology, the diagnosis of atherosclerosis (AS) is mainly focused on the later stage of AS development rather than plaque imaging in the period before plaque formation. It is impractical to apply the existing theoretical methods for the purpose of early detection of AS. Herein, this study uses a naphthalimide-based fluorescent probe for recognition of cellular reactive oxygen species (ROS). A platelet membrane (Mp) with foam cell targeting was wrapped around the probes to prepare two vesicle structures TBNG@Mp and GNTB@Mp. The animal experiment results show that the screened nano-detection system TBNG@Mp could accumulate in the thoracic aorta of early AS rats. Under the effect of intracellular ROS, fluorescence signals can be observed. In addition, acute biological toxicity was not observed in pathological sections. Therefore, the foam cell targeting system TBNG@Mp with acceptable biocompatibility can realize the detection of AS one to two decades in advance as well as has a good application prospect.

Reshaping the tumor microenvironment for increasing the distribution of glucose oxidase in tumor and inhibiting metastasis.

The poor penetration of solid tumors hinders the development of hunger therapy represented by glucose oxidase (GOx). To address this limitation, we have constructed a GOx/Dex@ZIF-TA nanosystem consisting of tannic acid (TA), carrier ZIF-8, encapsulated GOx and dexamethasone (Dex). In this nanosystem, the loaded Dex can not only expand the pores of the nucleus to promote GOx to enter the nucleus, addressing the shortcomings of short life of reactive oxygen species, but also inhibit the production of collagen to reshape the tumor microenvironment and inhibit lung metastasis. In vivo experiments proved that Dex could inhibit the production of collagen, which increased the accumulation and penetration of the tumor tissues and inhibited lung metastasis. In addition, cell experiments showed that Dex could also enlarge the nuclear pores of the nucleus and promote the entry of drugs into the nucleus. More importantly, Dex is a broad anti-inflammatory drug, and the results of this study should be easily transformed to achieve clinical benefits. Together, this work provided a way to address the limitations of hunger distribution in tumor tissues.

Ovalbumin-modified nanoparticles increase the tumor accumulation by a tumor microenvironment-mediated "giant".

We designed a pH intelligently driven self-assembled nano-platform (GOx@ZIF-OVA). The nano-platform was composed of glucose oxidase (GOx), ovalbumin (OVA) and zeolitic imidazolate skeleton-8 (ZIF-8). The goal was to address the depth and cumulative limits of the drug at the tumor site. Firstly, OVA-modified GOx@ZIF could greatly increase tumor accumulation due to spontaneous self-assembly from 142.2 ± 9.1 to 705.5 ± 52.1 nm and the 5779.4 ± 598.3 nm giant at pH values of 7.4, 6.5, and 5.0, respectively. More importantly, the tumor-like sphere experiments demonstrated that the encapsulated GOx "vampires" can cut off the energy source of tumors and poisonous tumor cells without depth limitations. Furthermore, immunofluorescence assay and cytotoxicity assay tests in vivo proved that T cell infiltration could be significantly increased, triggering an effective anti-tumor immune response and inhibiting lung metastasis. Therefore, the experimental results demonstrated that the acid-smart-driven nano-platform has the potential to address the limitations of tumor depth and drug accumulation in solid tumors.

ROS-boosted photodynamic therapy against metastatic melanoma by inhibiting the activity of antioxidase and oxygen-producing nano-dopants.

The antioxidant effect weakens the ability of PDT to resist melanoma, and the hypoxic tumor environment further restricts the application of photosensitizers in tumors. Therefore, to enhance the ability of PDT to resist melanoma, we designed a sequential enhanced PDT theranostic platform (Au@MTM-HA). Firstly, the nanotherapeutic platform uses TiO2 as a photosensitizer, which is doped with MnO2 to form a mesoporous MTM. The MTM can continuously provide oxygen, thereby increasing the level of reactive oxygen species (ROS) and reducing the metastatic effect by alleviating tumor hypoxia. Furthermore, the released Au25Sv9 could inhibit the activity of antioxidant defense enzymes and reduce the scavenging of ROS and further enhance the PDT effect. Simultaneously, surface-modified HA could not only recognize CD44 receptor but also act as a sealing agent for carriers. Result: Au@MTM-HA could explosively produce a 3-fold higher ROS and improve the PDT effect. Therefore, this work may provide strong evidence for Au@MTM-HA as a new and promising PDT candidate for the treatment of metastatic melanoma.

Construction and evaluation of tumor nucleus-targeting nanocomposite for cancer dual-mode imaging - Guiding photodynamic therapy/photothermal therapy.

To tackle the barrier of the insufficient intra-cellular delivery of reactive oxygen species (ROS) and heat, we designed a multifunctional nanoplatform to release ROS and heat directly in the cell nucleus for enhancing combined photodynamic therapy (PDT) and photothermal therapy (PTT) of tumors. As a photothermal agent, WS2 nanoparticles were adsorbed photosensitive Au25(Captopril)18- (Au25) nanoclusters via electrostatic interaction. And Dexamethasone (Dex), a glucocorticoid with nucleus targeting capability, played a key role in the intra-nuclear process of heat and ROS. PTT can increase intra-tumoral blood flow to promote Au25 produce more ROS for PDT. Under near infrared (NIR) laser irradiation at a single 808 nm, these nucleus targeting WS2 nanoplatforms showed a significant decreased cell viability of 18.2 ±â€¯1.7% and a high DNA damage degree of 59.6 ±â€¯8.3%. Furthermore, the WS2 nanoplatform could be further used for X-ray computed tomography (CT) images. Taken together, our study provided a new prospect for effectively diagnostic and enhancing PTT/PDT efficacy.

LncRNA UCA1 Promotes Mitochondrial Function of Bladder Cancer via the MiR-195/ARL2 Signaling Pathway.

BACKGROUND/AIMS: This study aims to identify whether Urothelial Cancer Associated 1 (UCA1) regulates mitochondrial metabolic reprogramming in bladder cancer, and to explore how UCA1 participates in mitochondrial metabolism by the UCA1/miR-195/ARL2 signaling pathway; these findings may be aid in the development of tumor diagnostic and therapeutic strategies. METHODS: Bladder tissues were obtained from patients. Stable cell lines were constructed, with ectopic expression of UCA1 in UMUC2 cells and knockdown of UCA1 in 5637 cells. The expression levels of UCA1, miR-195, and ARL2 were detected by real-time PCR, western blotting, and immunohistochemistry Cell viability was detected by Cell Counting Kit-8 (CCK8) assay; mitochondrial DNA copy numbers were tested by realtime PCR; ATP level was evaluated by ATP assay kit; mitochondrial membrane potential was analyzed by 5,5',6,6'-tetrachloro-1,1',3,3'- tetraethylbenzimidazolylcarbocyanine iodide (JC-1) fluorescent probe. miRNAs between UCA1 and ARL2 were predicted by TargetScan and RNAHybrid, and then determined by real-time PCR. Dual-luciferase activity assay and RNA immunoprecipitation (RIP) assay were used to verify the relationship between UCA1 and miR-195. The expression level of ARL2 was silenced by small interfering RNA(siRNA). For in vivo experiments, UCA1-silencing 5637 cells were subcutaneously injected into BALB/C nude mice to evaluate the effects of UCA1 on tumor progression by the regulation of miR-195 and ARL2. RESULTS: We demonstrate here that UCA1 enhances mitochondrial function in bladder cancer cells. UCA1 contributes to ARL2-induced mitochondrial activity, which plays an important role in mitochondrial function. UCA1, as a competing endogenous RNA (ceRNA), regulates mitochondrial function through upregulating ARL2. In this way, it inhibited the miR-195 signaling pathway to enhance mitochondrial function in bladder cancer. Additionally, ARL2 is a direct target of miR-195 and can be repressed by either miR-195 overexpression or UCA1 inhibition. Knockdown of ARL2 was analogous to the inhibition of UCA1 and the upregulation of miR-195. Animal experiments further indicated that UCA1 promoted bladder tumor growth by regulating miR-195 /ARL2. CONCLUSION: These data suggest that UCA1 enhanced mitochondrial function and cell viability through the UCA1/miR-195/ARL2 axis in vitro and in vivo. The elucidation of this signaling network provides a more adequate theoretical basis for understanding the molecular pathology of bladder cancer, and also UCA1 as a potential diagnosis and treatment target for bladder cancer.