Effectiveness of different intrusion modes of maxillary anterior teeth with mini-implants in clear aligner treatment: a three-dimensional finite element analysis.

BACKGROUND: The intrusion of maxillary anterior teeth is often required and there are various intrusion modes with mini-implants in clear aligner treatment. The objective of this study was to evaluate the effectiveness of maxillary anterior teeth intrusion with different intrusion modes, aiming to provide references for precise and safe intrusion movements in clinical practice. METHODS: Cone-beam computed tomography and intraoral optical scanning data of a patient were collected. Finite element models of the maxilla, maxillary dentition, periodontal ligaments (PDLs), clear aligner (CA), attachments, and mini-implants were established. Different intrusion modes of the maxillary anterior teeth were simulated by changing the mini-implant site (between central incisors, between central and lateral incisor, between lateral incisor and canine), loading site (between central incisors, on central incisor, between central and lateral incisor, between lateral incisor and canine), and loading mode (labial loading and labiolingual loading). Ten conditions were generated and intrusive forces of 100 g were applied totally. Then displacement tendency of the maxillary anterior teeth and CA, and stress of the PDLs were analyzed. RESULTS: For the central incisor under condition L14 and for the canine under conditions L11, L13, L23, and L33, the intrusion amount was negative. Under other conditions, the intrusion amount was positive. The labiolingual angulation of maxillary anterior teeth exhibited positive changes under all conditions, with greater changes under linguoincisal loading. The mesiodistal angulation of canine exhibited positive changes under labial loading, while negative changes under linguoincisal loading except for condition L14. CONCLUSIONS: The intrusion amount, labiolingual and mesiodistal angulations of the maxillary anterior teeth were affected by the mini-implant site, loading site, and loading mode. Labial and linguoincisal loading may have opposite effects on the intrusion amount of maxillary anterior teeth and the mesiodistal angulation of canine. The labiolingual angulation of the maxillary incisors would increase under all intrusion modes, with greater increases under linguoincisal loading.

Building social identity-based groups to enhance online peer support for patients with chronic disease: a pilot study using mixed-methods evaluation.

Online peer support is increasingly important to encourage patients with chronic diseases to engage in successful self-management. However, studies mainly focus on individual-level participation and have not fully explored how to maximize the impact of online peer support through group identification. In this study, we aim to build an online social identity-based group to examine the impact of group identity on peer support. Twenty-five participants who completed the first phase of a larger study were randomly assigned either to the treatment group (identity-based group level, n = 15, three subgroups, five members in each subgroup) or to the control group (individual-level, n = 10). All participants in both treatment and control groups received the same tasks and incentives. Peer support behavior (informational support and emotional support), task completion (knowledge learning, self-tracking behavior), and health-related outcomes (self-efficacy [SE] and HbA1c) were collected for qualitative and quantitative analysis. Results from a 3-month pilot experiment showed that the treatment group offered substantial enhancement in peer support compared to the control group. It also significantly promoted improvement in SE. However, there was no significant difference in task completion or changes in HbA1c between the two groups. The results of the content analysis suggest that having a team leader, timely responsiveness, and intergroup competition played important roles in building social identity-based online groups and subsequently generating peer support. We provide some encouraging results that indicate how online groups may be effectively designed to promote peer support.

Influence of Personality on mHealth Use in Patients with Diabetes: Prospective Pilot Study.

BACKGROUND: Mobile technology for health (mHealth) interventions are increasingly being used to help improve self-management among patients with diabetes; however, these interventions have not been adopted by a large number of patients and often have high dropout rates. Patient personality characteristics may play a critical role in app adoption and active utilization, but few studies have focused on addressing this question. OBJECTIVE: This study aims to address a gap in understanding of the relationship between personality traits and mHealth treatment for patients with diabetes. We tested the role of the five-factor model of personality traits (openness to experience, conscientiousness, extraversion, agreeableness, and neuroticism) in mHealth adoption preference and active utilization. METHODS: We developed an mHealth app (DiaSocial) aimed to encourage diabetes self-management. We recruited 98 patients with diabetes-each patient freely chose whether to receive the standard care or the mHealth app intervention. Patient demographic information and patient personality characteristics were assessed at baseline. App usage data were collected to measure user utilization of the app. Patient health outcomes were assessed with lab measures of glycated hemoglobin (HbA1c level). Logistic regression models and linear regression were employed to explore factors predicting the relationship between mHealth use (adoption and active utilization) and changes in health outcome. RESULTS: Of 98 study participants, 46 (47%) downloaded and used the app. Relatively younger patients with diabetes were 9% more likely to try and use the app (P=.02, odds ratio [OR] 0.91, 95% CI 0.85-0.98) than older patients with diabetes were. Extraversion was negatively associated with adoption of the mHealth app (P=.04, OR 0.71, 95% CI 0.51-0.98), and openness to experience was positively associated with adoption of the app (P=.03, OR 1.73, 95% CI 1.07-2.80). Gender (P=.43, OR 0.66, 95% CI 0.23-1.88), education (senior: P=.99, OR 1.00, 95% CI 0.32-3.11; higher: P=.21, OR 2.51, 95% CI 0.59-10.66), and baseline HbA1c level (P=.36, OR 0.79, 95% CI 0.47-1.31) were not associated with app adoption. Among those who adopted the app, a low education level (senior versus primary P=.003; higher versus primary P=.03) and a high level of openness to experience (P=.048, OR 2.01, 95% CI 1.01-4.00) were associated with active app utilization. Active users showed a significantly greater decrease in HbA1c level than other users (ΔHbA1c=-0.64, P=.05). CONCLUSIONS: This is one of the first studies to investigate how different personality traits influence the adoption and active utilization of an mHealth app among patients with diabetes. The research findings suggest that personality is a factor that should be considered when trying to identify patients who would benefit the most from apps for diabetes management.

Root canal morphology of maxillary and mandibular first premolars analyzed using cone-beam computed tomography in a Shandong Chinese population.

The aim of this study was to explore the root morphology and root canal configuration of first premolars among Shandong Chinese residents using cone-beam computed tomography (CBCT).Randomly selected CBCT images were collected from 648 patients (44% women, 56% men). In total, 1268 maxillary and 1296 mandibular first premolars were analyzed. The number of roots and the canal configuration were recorded and identified based on Vertucci's classification.The majority of the maxillary first premolars had 1 root (67.4%), followed by 2 roots (32%). A 2-canal configuration (89%) was the most prevalent observation. For mandibular first premolars, 98.8% had 1 root and 81% presented the type I configuration. There were no statistical differences in the number of roots or morphology in terms of the left/right side or sex (P > .05).Among Chinese residents, the majority of maxillary first premolars had 1 root and 2 canals, whereas the most common anatomical configuration for mandibular first premolars was 1 root with 1 canal.

Apigenin attenuates oxidative stress and neuronal apoptosis in early brain injury following subarachnoid hemorrhage.

Apigenin (API) is a naturally occurring plant flavone that exhibits powerful antioxidant and antiapoptosis. Oxidative stress plays an important role in the pathogenesis of early brain injury (EBI) following subarachnoid hemorrhage (SAH). The potential anti-oxidative and anti-apoptosis effects of API on EBI following SAH, however, have not been elucidated. The aim of this study was to assess whether API alleviates EBI after SAH via its anti-oxidative and anti-apoptotic effects. The endovascular puncture model was used to induce SAH and all the rats were subsequently sacrificed at 24h after SAH. Our data demonstrated that administration of API could significantly alleviate EBI (including neurological deficiency, brain edema, blood-brain barrier permeability, and cortical cell apoptosis) after SAH in rats. Meanwhile, API treatment reduced the reactive oxygen species (ROS) level and the concentration of malondialdehyde (MDA) and myeloperoxidase (MPO), elevated the ratio of glutathione (GSH) and oxidized glutathione (GSSG), and increased the amount of super-oxide dismutase (SOD) and hydrogen peroxide in brain cortex at 24h following SAH. Moreover, API treatment inhibited SAH-induced the expression of Bax and caspase-3, significantly reduced neuronal apoptosis. Collectively, API exerts its neuroprotective effect likely through the dual activities of anti-oxidation and anti-apoptosis, at least partly. These data provide a basic platform to consider API may be safely used as a potential drug for treatment of SAH.

Naringin alleviates early brain injury after experimental subarachnoid hemorrhage by reducing oxidative stress and inhibiting apoptosis.

This study aims to clarify the neuroprotective effect of naringin on early brain injury (EBI) following subarachnoid hemorrhage (SAH) and the possible mechanisms of naringin in the treatment of SAH. The endovascular puncture model was performed to induce SAH model in rats and the efficacy of 40mg/kg and 80mg/kg naringin were tested by intraperitoneally administration. SAH grade, neurological score, brain edema, blood-brain barrier permeability, the changes of oxidative stress related factors, apoptosis-related proteins, mitogen-activated protein kinase (MAPK) signaling pathway and neuronal morphology were detected to analyze the potential effect of naringin against SAH. The results demonstrated that naringin significantly ameliorated EBI, including SAH severity, neurologic deficits, brain edema and blood-brain barrier integrity by attenuating SAH-induced oxidative stress and apoptosis, and reduced the oxidant damage and apoptosis by inhibiting the activation of MAPK signaling pathway, which suggested a therapeutic potential of naringin in providing neuroprotection after SAH.

Fangchinoline suppresses the growth and invasion of human glioblastoma cells by inhibiting the kinase activity of Akt and Akt-mediated signaling cascades.

Glioblastoma multiforme (GBM) is one of the most palindromic and malignant central nervous system neoplasms, and the current treatment is not effectual for GBM. Research of specific medicine for GBM is significant. Fangchinoline possesses a wide range of pharmacological activities and attracts more attentions due to its anti-tumor effects. In this study, two WHO grade IV human GBM cell lines (U87 MG and U118 MG) were exposed to fangchinoline, and we found that fangchinoline specifically inhibits the kinase activity of Akt and markedly suppresses the phosphorylation of Thr308 and Ser473 of Akt in human GBM cells. We also observed that fangchinoline inhibits tumor cell proliferation and invasiveness and induces apoptosis through suppressing the Akt-mediated signaling cascades, including Akt/p21, Akt/Bad, and Akt/matrix metalloproteinases (MMPs). These data demonstrated that fangchinoline exerts its anti-tumor effects in human glioblastoma cells, at least partly by inhibiting the kinase activity of Akt and suppressing Akt-mediated signaling cascades.

Reversion of malignant phenotypes of human glioblastoma cells by ß-elemene through ß-catenin-mediated regulation of stemness-, differentiation- and epithelial-to-mesenchymal transition-related molecules.

BACKGROUND: Glioblastoma is the most common and lethal type of primary brain tumor. ß-Elemene, a natural plant drug extracted from Curcuma wenyujin, has shown strong anti-tumor effects in various tumors with low toxicity. However, the effects of ß-elemene on malignant phenotypes of human glioblastoma cells remain to be elucidated. Here we evaluated the effects of ß-elemene on cell proliferation, survival, stemness, differentiation and the epithelial-to-mesenchymal transition (EMT) in vitro and in vivo, and investigated the mechanisms underlying these effects. METHODS: Human primary and U87 glioblastoma cells were treated with ß-elemene, cell viability was measured using a cell counting kit-8 assay, and treated cells were evaluated by flow cytometry. Western blot analysis was carried out to determine the expression levels of stemness markers, differentiation-related molecules and EMT-related effectors. Transwell assays were performed to further determine EMT of glioblastoma cells. To evaluate the effect of ß-elemene on glioblastoma in vivo, we subcutaneously injected glioblastoma cells into the flank of nude mice and then intraperitoneally injected NaCl or ß-elemene. The tumor xenograft volumes were measured every 3 days and the expression of stemness-, differentiation- and EMT-related effectors was determined by Western blot assays in xenografts. RESULTS: ß-Elemene inhibited proliferation, promoted apoptosis, impaired invasiveness in glioblastoma cells and suppressed the growth of animal xenografts. The expression levels of the stemness markers CD133 and ATP-binding cassette subfamily G member 2 as well as the mesenchymal markers N-cadherin and ß-catenin were significantly downregulated, whereas the expression levels of the differentiation-related effectors glial fibrillary acidic protein, Notch1, and sonic hedgehog as well as the epithelial marker E-cadherin were upregulated by ß-elemene in vitro and in vivo. Interestingly, the expression of vimentin was increased by ß-elemene in vitro; this result was opposite that for the in vivo procedure. Inhibiting ß-catenin enhanced the anti-proliferative, EMT-inhibitory and specific marker expression-regulatory effects of ß-elemene. CONCLUSIONS: ß-Elemene reversed malignant phenotypes of human glioblastoma cells through ß-catenin-involved regulation of stemness-, differentiation- and EMT-related molecules. ß-Elemene represents a potentially valuable agent for glioblastoma therapy.

Apigenin protects blood-brain barrier and ameliorates early brain injury by inhibiting TLR4-mediated inflammatory pathway in subarachnoid hemorrhage rats.

Early brain injury (EBI) following subarachnoid hemorrhage (SAH) is associated with high morbidity and mortality. Inflammation has been considered as the major contributor to brain damage after SAH. SAH induces a systemic increase in pro-inflammatory cytokines and chemokines. Disruption of blood-brain barrier (BBB) facilitates the influx of inflammatory cells. It has been reported that the activation of toll-like receptor 4 (TLR4)/NF-κB signaling pathway plays a vital role in the central nervous system diseases. Apigenin, a common plant flavonoid, possesses anti-inflammation effect. In this study, we focused on the effects of apigenin on EBI following SAH and its anti-inflammation mechanism. Our results showed that apigenin (20mg/kg) administration significantly attenuated EBI (including brain edema, BBB disruption, neurological deficient, severity of SAH, and cell apoptosis) after SAH in rats by suppressing the expression of TLR4, NF-κB and their downstream pro-inflammatory cytokines in the cortex and by up-regulating the expression of tight junction proteins of BBB. Double immunofluorescence staining demonstrated that TLR4 was activated following SAH in neurons, microglia cells, and endothelial cells but not in astrocytes. Apigenin could suppress the activation of TLR4 induced by SAH and inhibit apoptosis of cells in the cortex. These results suggested that apigenin could attenuate EBI after SAH in rats by suppressing TLR4-mediated inflammation and protecting against BBB disruption.

Stanniocalcin-1, a new biomarker of glioma progression, is associated with prognosis of patients.

Stanniocalcin-1 (STC1) is a secreted glycoprotein hormone and highly expressed in various types of human malignancies. Although evidence points to the role of STC1 in human cancers, the clinical significance of STC1 expression in glioma has not been established. Here, we investigated the relationship between STC1 expression and clinicopathological significance in glioma. In our study, we selected 60 cases of different grades glioma tissues to detect the expression of STC1. Data showed that the mRNA and protein levels of STC1 in high-grade glioma tissues were significantly higher than that in low-grade tissues. The results of double immunofluorescent staining disclosed STC1 distribution in vascular endothelial cells and the cytoplasm in high-grade glioma, but almost distributed only in vascular endothelial cells in low-grade glioma. By immunohistochemistry, we got the same results and the expression of STC1 has significant difference in high-grade gliomas and low-grade gliomas. Furthermore, the results of Kaplan-Meier analysis indicated that cases with high STC1expression had significantly worse overall survival than those with low level of STC1. These results suggested that STC1 may be a valuable biomarker in diagnosing malignant degree of glioma and evaluating prognostic following surgery. Next, we would study the pathophysiological mechanism of STC1 in glioma.

Fangchinoline as a kinase inhibitor targets FAK and suppresses FAK-mediated signaling pathway in A549.

BACKGROUND: Fangchinoline as a novel anti-tumor agent has been paid attention in several types of cancers cells except lung cancer. Here we have investigated the effect of fangchinoline on A549 cells and its underlying mechanism. PURPOSE: The purpose of this work was to study the effect of fangchinoline on A549 cells. METHODS: Four lung cancer cell lines (A549, NCI-H292, NCI-H446, and NCI-H460) were exposed to varying concentrations (10-40 µmol/l) of fangchinoline to observe the effect of fangchinoline on the four lung cancer cell lines and to observe the changes of the lung cancer cell on proliferation, apoptosis, and invasion. RESULTS: Fangchinoline effectively suppressed proliferation and invasion of A549 cell line but not NCI-H292, NCI-H446, and NCI-H460 cell lines by inhibiting the phosphorylation of FAK (Tyr397) and its downstream pathways, due to the significant differences of Fak expression between A549 and the other three cell lines. And all FAK-paxillin/MMP2/MMP9 pathway, FAK-Akt pathway, and FAK-MEK-ERK1/2 pathway could be inhibited by fangchinoline. DISCUSSION: Fangchinoline effectively suppressed proliferation and invasion of A549 cell line by inhibiting the phosphorylation of FAK (Tyr397) and its downstream pathways. CONCLUSION: Fangchinoline could inhibit the phosphorylation of FAK(p-Tyr397), at least partially. Fangchinoline as a kinase inhibitor targets FAK and suppresses FAK-mediated signaling pathway and inhibits the growth and the invasion in tumor cells which highly expressed FAK such as A549 cell line.

Oxymatrine targets EGFR(p-Tyr845) and inhibits EGFR-related signaling pathways to suppress the proliferation and invasion of gastric cancer cells.

PURPOSE: Oxymatrine (matrine oxide, matrine N-oxide, matrine 1-oxide) is one of the quinolizidine alkaloid compounds extracted from the root of Sophora flavescens (a traditional Chinese herb). Oxymatrine has been known for its chemoresistance and cytotoxic effects on various cancer cells, but the mechanism underlying has not been explored. We study the mechanism of oxymatrine on gastric cells. METHODS: We observed the changes of proliferation, apoptosis and invasion in human gastric cells by detecting the signaling pathway in which oxymatrine plays role. RESULTS: These results showed that oxymatrine inhibited the proliferation and invasion of gastric cells through inhibition of EGFR/Cyclin D1/CDK4/6, EGFR/Akt and MEK-1/ERK1/2/MMP2 pathway by inhibiting EGFR(p-Tyr845). In addition to inducing gastric cells apoptosis, oxymatrine significantly inhibited the migration and invasion of human gastric cancer cells by decreasing phospho-Cofilin (Ser3) and phospho-LIMK1 (Thr508) without changing the total Cofilin and LIMK1 expression. CONCLUSION: Oxymatrine effectively suppressed the phosphorylation of EGFR (Tyr845), and EGFR was the target of oxymatrine.

Ursolic acid alleviates early brain injury after experimental subarachnoid hemorrhage by suppressing TLR4-mediated inflammatory pathway.

Our previous studies proved that ursolic acid (UA) protected against early brain injury (EBI) by modulating oxidative stress after experimental subarachnoid hemorrhage (SAH), but it has not been evaluated yet about its effects on an inflammatory pathway in a SAH model. This study was undertaken to evaluate the influence of UA on the toll-like receptor 4 (TLR4) signaling pathway after SAH. Adult male SD rats were divided into vehicle-treated sham, vehicle-treated SAH, and UA-treated SAH groups. The endovascular puncture model was used to induce SAH and all the rats were subsequently sacrificed at 48 h after SAH. UA administration markedly decreased the expressions of TLR4 pathway-related agents, such as intercellular adhesion molecule-1 (ICAM-1), TLR4, nuclear factor-κB (NF-κB) P65, interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), inducible nitric oxide synthase (iNOS) and matrix metalloproteinase (MMP)-9. Apoptosis detected by TUNEL indicated that fewer positive cells appeared in UA administration SAH groups than the control group. In conclusion, UA may attenuate EBI after SAH in rats by suppressing the TLR4-mediated inflammatory pathway.

Autophagy activation contributes to the neuroprotection of remote ischemic perconditioning against focal cerebral ischemia in rats.

Remote ischemic perconditioning (RIPer) has been proved to provide potent cardioprotection. However, there are few studies on neuroprotection of RIPer. This study aims to clarify the neuroprotective effect of RIPer and the role of autophagy induced by RIPer against cerebral ischemia reperfusion injury in rats. Using a transient middle cerebral artery occlusion (MCAO) model in rats to imitate focal cerebral ischemia. RIPer was carried out 4 cycles of 10 min ischemia and 10 min reperfusion, with a thin elastic band tourniquet encircled on the bilateral femoral arteries at the start of 10 min after MCAO. Autophagy inhibitor 3-methyladenine (3-MA) and autophagy inducer rapamycin were administered respectively to determine the contribution of autophagy in RIPer. Neurologic deficit scores, infarct volume, brain edema, Nissl staining, TUNEL assay, immunohistochemistry and western blot was performed to analyze the neuroprotection of RIPer and the contribution of autophagy in RIPer. RIPer significantly exerted neuroprotective effects against cerebral ischemia reperfusion injury in rats, and the autophagy-lysosome pathway was activated by RIPer treatment. 3-MA reversed the neuroprotective effects induced by RIPer, whereas rapamycin ameliorated the brain ischemic injury. Autophagy activation contributes to the neuroprotection by RIPer against focal cerebral ischemia in rats.

Ursolic acid reduces oxidative stress to alleviate early brain injury following experimental subarachnoid hemorrhage.

Ursolic acid (UA), a well-known anti-oxidative reagent, has been reported to protect the brain against ischemic stoke. However, the potential role of UA in protecting against early brain injury (EBI) after subarachnoid hemorrhage (SAH) remains unclear. The present study aimed to examine the effect of UA against EBI following SAH, and to demonstrate whether the effect is associated with its powerful antioxidant property. Male SD rats were divided into vehicle-treated sham, vehicle-treated SAH, and UA-treated SAH groups. The endovascular puncture model was used to induce SAH and all the rats were subsequently sacrificed at 48h after SAH. The results show that UA administration could significantly attenuate EBI (including brain edema, blood-brain barrier disruption, neural cell apoptosis, and neurological deficient) after SAH in rats and up-regulate the antioxidative levels in the rat cerebral cortex, suggesting that administration of UA in experimental SAH rats could alleviate brain injury symptom, potentially through its powerful antioxidant property. Hence, we concluded that UA might be a novel therapeutic agent for EBI following SAH.

ß-elemene inhibits stemness, promotes differentiation and impairs chemoresistance to temozolomide in glioblastoma stem-like cells.

Accumulating evidence indicates that glioblastoma stem-like cells (GSCs) are key factors in tumour development, recurrence and chemoresistance. The impairment of stemness and the enhancement of differentiation contributes to the weakening of radiation and chemotherapy resistance of GSCs. We previously found that ß-elemene was an effective anti-glioblastoma agent and chemosensitizer. In this study, we examined the distribution of CD133(+) cells in human glioblastoma tissues by immunohistochemistry. Following treatment with ß-elemene, the formation of GSC spheres was investigated by manual counting, the proliferation of GSCs was measured with a Cell Counting Kit-8 (CCK-8) assay, and the dispersion of GSC spheres was observed with an inverted microscope. GSC spheres were treated with ß-elemene, and the expression levels of CD133, ATP-binding cassette subfamily G member 2 (ABCG2) and glial fibrillary acidic protein (GFAP) were examined by western blotting. After treatment with ß-elemene, the volumes and weights of GSC xenografts were measured, and the expression of CD133, ABCG2 and GFAP was evaluated through immunohistochemistry analysis. After treatment with ß-elemene and temozolomide (TMZ), GSC viability was examined by the CCK-8 assay, and the volumes and weights of xenografts were measured. We found that CD133(+) cells were assembled in some vascular walls and also sparsely distributed in other parts of glioblastoma tissues. ß-elemene decreased the formation of GSC spheres, dispersed GSC spheres and inhibited the proliferation of GSCs in vitro and in vivo. In the GSC spheres and xenografts treated with ß-elemene, the expression of CD133 and ABCG2 was significantly downregulated, and the expression of GFAP increased. Furthermore, the sensitivity of GSCs to TMZ was enhanced in vitro and in vivo. These results suggest that ß-elemene impaired the stemness of GSC spheres, promoted their differentiation and sensitized GSCs to TMZ. ß-elemene will hopefully become a valuable agent to enhance the effects of radiotherapy and chemotherapy.