Non-coding RNAs Function in Periodontal Ligament Stem Cells.

Non-coding RNA has many types which has rich functions and plays an important role in the study of basic molecular mechanisms. Many non-coding RNA have important implications for pluripotent stem cells and embryonic stem cells. It has been found to affect the self-renewal and osteogenesis of many types of stem cells. They have also been found to regulate stem cell proliferation and induct bone differentiation. Periodontal ligament stem cells are essential for the regeneration of periodontal tissue. In recent years, in the field of stomatology, studies have found that many non-coding RNA also have significant regulatory effects on the proliferation and differentiation of periodontal stem cells and may become potential therapeutic targets for many common periodontal diseases such as periodontitis, bone/tooth/soft tissue loss and orthodontic treatment. Therefore, we summarized the current research status of non-coding RNA in the field of molecular mechanism of periodontal ligament stem cells and prospected its future progress.

Comparison between basal arch width in normal occlusions and class â ¡ malocclusions by using cone-beam computed tomography.

Objective: The purpose of this research was to investigate the measurements of maxillary and mandibular basal arch width in male and female with normal occlusion, and to compare dental arch width difference between normal occlusion and ClassⅡ malocclusion groups could be helpful in orthodontic diagnosis and treatment planning. Methods: Cone-beam computed tomography (CBCT) images from 133 individuals (76 males and 57 females) with normal occlusion and 64 (25 males and 39 females) with skeletal Class II malocclusions were evaluated. The distances between canines, first molars (basal arch widths: BAW) and second molars were measured from CRs (center of resistance) of the teeth and the projection of first molars on buccal bones (WALA distance) were measured. Results: There were significant differences in male and female maxillary and mandibular dental transverse widths. The normal range of the maxilla and mandible basal bone widths differences were -2 mm-2 mm (-0.05 ± 2.17 mm). The normal occlusion and Class Ⅱ groups exhibited significant differences in the width of the intercanine and first molars. Sella-nasion-A point angle (SNA) and Sella-nasion-B point angle (SNB) in the Class Ⅱ male group were positively correlated with the width between the maxillary canines. For individuals with normal occlusions, the width of the mandible at the second molar was greater than that of the maxilla, so more attention should be paid to the width of the second molar when considering clinical treatment. Conclusion: Measuring the width of the maxilla and mandible basal bones from the resistance center of the first molar was a feasible and repeatable method can be used in clinical practice. The data could serve as a reference for orthodontic treatment planning. More consideration should be paid to the horizontal dental problems of the treatment plan for Class Ⅱ patients. And the width of the mandible at the second molar was greater than that of the maxilla, so more attention should be paid during treatment.

Biomechanical effects of different staging and attachment designs in maxillary molar distalization with clear aligner: a finite element study.

BACKGROUND: In the present study, the effects of distalizations of one and two molars with different step distances and attachment designs have been analyzed. METHODS: A 3D finite element analysis model has been developed in order to determine the tendency of tooth displacement and stress distribution with clear aligner treatment. RESULTS: Under the condition of single-molar distalization, when the step distance was set to 0.25 mm, the total displacement was 0.086 mm for central incisors, 0.080 mm for lateral incisors, 0.084 mm for canines, 0.102 mm for the first premolar and 0.076 mm for the second premolar. The von Mises stress of roots and the principal stress of the periodontal ligament was slightly lower than in the control group when the step distance was set to 0.130 mm. Under the condition of two-molar distalization, when the step distance was set to 0.130 mm, the total displacements for central incisors, lateral incisors and canines as well as both the first and second maxillary molars were basically the same as with a distance of 0.250 mm for one-molar distalization. In addition, when the step distance was 0.130 mm with two-molar distalization, the rotation center of the first and second molar was closer to the apex of the root indicating that the smaller step distance led to more bodily movement during the two-molar distalization. However, displacement tendencies of the first molar and the second molar were basically the same whether horizontal or vertical rectangular attachments were added. CONCLUSIONS: A step distance of moving two molars to 0.130 mm can achieve the same reaction force on the anterior teeth as moving one molar 0.250 mm without effects on horizontal or vertical rectangular attachments. CLINICAL RELEVANCE: Our results provide a theoretical basis and guidance for simultaneously moving two molars backward in clinical practice using a clear aligner.

LncRNA00638 promotes the osteogenic differentiation of periodontal mesenchymal stem cells from periodontitis patients under static mechanical strain.

BACKGROUND: The osteogenic differentiation capacity of periodontal mesenchymal stem cells (PDLSCs) can be influenced by different levels of static mechanical strain (SMS) in an inflammatory microenvironment. Long non-coding RNAs (lncRNAs) are involved in various physiological processes. However, the mechanisms by which lncRNAs regulate the osteogenic differentiation of PDLSCs remain unclear. METHODS: We investigated the responses of PDLSCs obtained from periodontitis patients and healthy people to 8% and 12%SMS. Gene microarray and bioinformatics analyses were implemented and identified lncRNA00638 as a target gene for the osteogenesis of PDLSCs from periodontitis patients under SMS. Competing endogenous RNA (ceRNA) network analysis was applied and predicted interactions among lncRNA00638, miRNA-424-5p, and fibroblast growth factor receptor 1 (FGFR1). Gene expression levels were regulated by lentiviral vectors. Cell Counting Kit-8 assays, alkaline phosphatase assays, and Alizarin Red S staining were used to examine the osteogenic potential. RT-qPCR and Western blot were performed to detect the expression levels of related genes and proteins. RESULTS: We found that 8% and 12% SMS exerted distinct effects on HPDLSCs and PPDLSCs, with 12% SMS having the most significant effect. By microarray analysis, we detected differentially expressed lncRNAs/mRNAs between 12% SMS strained and static PPDLSCs, among which lncRNA00638 was detected as a positive target gene to promote the osteogenic differentiation of PPDLSCs under SMS loading. Mechanistically, lncRNA00638 may act as a ceRNA for miR-424-5p to compete with FGFR1. In this process, lncRNA00638 and miR-424-5p suppress each other and form a network to regulate FGFR1. CONCLUSIONS: Our findings demonstrate that the lncRNA00638/miRNA-424-5p/FGFR1 regulatory network is actively involved in the regulation of PDLSC osteogenic differentiation from periodontitis patients under SMS loading, which may provide evidence for optimizing orthodontic treatments in patients with periodontitis.

Comparison of pedicle screw fixation with or without cement augmentation for treating single-segment isthmic spondylolisthesis in the osteoporotic spine.

The present study examined the necessity of cement-augmented pedicle screw fixation in osteoporotic patients with single-segment isthmic spondylolisthesis.Fifty-nine cases were reviewed retrospectively. Thirty-three cases were in the polymethylmethacrylate-augmented pedicle screw (PMMA-PS) group, and the other 26 cases were in the conventional pedicle screw (CPS) group. Evaluation data included operation time, intraoperative blood loss, hospitalization cost, hospitalization days, rates of fusion, screw loosening, bone cement leakage, visual analogue scale (VAS) scores, Oswestry disability index (ODI), lumbar lordosis (LL), pelvic tilt (PT) and sacral slope (SS).The operation time and blood loss in the CPS group decreased significantly compared to those in the PMMA-PS group. The average hospitalization cost of the PMMA-PS group was significantly higher than that of the CPS group. There was no significant difference in the average hospital stay between the 2 groups. The initial and last follow-up postoperative VAS and ODI scores improved significantly in the two groups. There were no significant differences in VAS and ODI between the 2 groups at each time point. The last postoperative spine-pelvic parameters were significantly improved compared with those preoperatively. In the PMMA-PS group, the fusion rate was 100%. The fusion rate was 96.15% in the CPS group. No significant difference was found between the two groups for the fusion rate. Nine patients in the PMMA-PS group had bone cement leakage. There was no screw loosening in the PMMA-PS group. There were 2 cases of screw loosening in the CPS group. There were no significant differences in screw loosening, postoperative adjacent segment fractures, postoperative infection or postoperative revision between the 2 groups. The use of PMMA-PS on a regular basis is not recommended in posterior lumbar interbody fusion for the treatment of single-segment isthmic spondylolisthesis with osteoporosis.

Ablation of Shank3 alleviates cardiac dysfunction in aging mice by promoting CaMKII activation and Parkin-mediated mitophagy.

Compromised mitophagy and mitochondrial homeostasis are major contributors for the etiology of cardiac aging, although the precise underlying mechanisms remains elusive. Shank3, a heart-enriched protein, has recently been reported to regulate aging-related neurodegenerative diseases. This study aimed to examine the role of Shank3 in the pathogenesis of cardiac senescence and the possible mechanisms involved. Cardiac-specific conditional Shank3 knockout (Shank3CKO) mice were subjected to natural aging. Mitochondrial function and mitophagy activity were determined in vivo, in mouse hearts and in vitro, in cardiomyocytes. Here, we showed that cardiac Shank3 expression exhibited a gradual increase during the natural progression of the aging, accompanied by overtly decreased mitophagy activity and a decline in cardiac function. Ablation of Shank3 promoted mitophagy, reduced mitochondria-derived superoxide (H2O2 and O2•-) production and apoptosis, and protected against cardiac dysfunction in the aged heart. In an in vitro study, senescent cardiomyocytes treated with D-gal exhibited reduced mitophagy and significantly elevated Shank3 expression. Shank3 knock-down restored mitophagy, leading to increased mitochondrial membrane potential, decreased mitochondrial oxidative stress, and reduced apoptosis in senescent cardiomyocytes, whereas Shank3 overexpression mimicked D-gal-induced mitophagy inhibition and mitochondrial dysfunction in normally cultured cardiomyocytes. Mechanistically, the IP assay revealed that Shank3 directly binds to CaMKII, and this interaction was further increased in the aged heart. Enhanced Shank3/CaMKII binding impedes mitochondrial translocation of CaMKII, resulting in the inhibition of parkin-mediated mitophagy, which ultimately leads to mitochondrial dysfunction and cardiac damage in the aged heart. Our study identified Shank3 as a novel contributor to aging-related cardiac damage. Manipulating Shank3/CaMKII-induced mitophagy inhibition could thus be an optional strategy for therapeutic intervention in clinical aging-related cardiac dysfunctions.

Investigating the mechanical effect of the sagittal angle of the cervical facet joint on the cervical intervertebral disc.

Background: Facet tropism is defined as the asymmetry between the left and right facet joints relative to the sagittal plane. Published clinical studies have found that facet tropism is associated with cervical disc herniation. However, the relationship between the facet orientation and the side of cervical disc herniation remains controversial. Therefore, this study used the finite-element technique to investigate the biomechanical effects of the sagittal angle of the cervical facet joints on the cervical intervertebral disc. Objective: The biomechanical effects of the sagittal angle of the cervical facet joint on the cervical disc and facet joint were investigated using the finite-element technique. Methods: The finite-element model was constructed using computed tomography scans of a 26-year-old female volunteer. First, a cervical model was constructed from C3 to C7. The model was verified using data from previously published studies. Second, the facet orientation at the C5-C6 level was altered to simulate different sagittal angles of cervical facet joints. Five models, F70, F80, F90, F100, and F110, were simulated with different facet joint orientations (70°, 80°, 90°, 100°, and 110° facet joint angles at the left side, respectively, and 90° facet joint angles at the right side) at the C5-C6 facet joints. In each model, annular fibres stress and facet cartilage pressure were studied under six pure moments and two combined moments. Results: Comparing the stress of the annulus fibres in flexion combined with right axial rotation and in flexion combined with left axial rotation in the same model, no difference in the maximum stress of the annulus fibres was noted between these two different moments in the F90 model, whereas differences of 12.80%, 8.84%, 14.95% and 33.32% were noted in the F70, F80, F100 and F110 models, respectively. The same trend was observed when comparing the maximum stress of the annulus fibres in each model during left and right axial rotation. No differences in annular fibres stress and facet cartilage pressure were noted among the five models in flexion, extension, lateral bending, left axial rotation, and flexion combined with left axial rotation in this study. However, compared with the F70 model in flexion combined with right axial rotation, the annulus fibres stress of the F80, F90, F100, and F110 models increased by 5.53%, 13.03%, 35.04%, and 72.94%, respectively, and the pressure of the left facet joint of these models decreased by 5.65%, 12.10%, 18.41%, and 25.74%, respectively. The same trend was observed in the right axial moment. Conclusion: Facet tropism leads to unbalanced stress distribution on the annulus fibres at the cervical intervertebral disc. The greater the sagittal angle of the facet joint, the greater the annular fibres stress on this side. We hypothesised that the side with the larger sagittal angle of the facet joint exhibits a greater risk of disc herniation.

Three-Dimensional Poly-(ε-Caprolactone) Nanofibrous Scaffolds Promote the Maturation of Human Pluripotent Stem Cells-Induced Cardiomyocytes.

Although pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) have been proved to be a new platform for heart regeneration, the lack of maturity significantly hinders the clinic application. Recent researches indicate that the function of stem cell is associated with the nanoscale geometry/topography of the extracellular matrix (ECM). However, the effects of 3D nanofibrous scaffolds in maturation of iPSC-CMs still remain unclear. Thus, we explored the effects of restructuring iPSC-CMs in 3D nano-scaffolds on cell morphology, cardiac-specific structural protein, gap junction and calcium transient kinetics. Using the electrospinning technology, poly-(ε-caprolactone) (PCL) nanofibrous scaffold were constructed and iPSC-CMs were seeded into these forms. As expected, strong sarcolemmal remodeling processes and myofilament reorientation were observed in 3D nano-scaffolds culture, as well as more expression of cardiac mature proteins, such as ß-MHC and MLC2v. The mature morphology of 3D-shaped iPSC-CMs leaded to enhanced calcium transient kinetics, with increased calcium peak transient amplitude and the maximum upstroke velocity (Vmax). The results revealed that the maturation of iPSC-CMs was enhanced by the electrospun 3D PCL nanofibrous scaffolds treatment. These findings also proposed a feasible strategy to improve the myocardium bioengineering by combining stem cells with scaffolds.

Profiles of facial soft tissue changes during and after orthodontic treatment in female adults.

BACKGROUND: Some female adults who received orthodontic treatment often complain about thinner faces, protruding cheekbones and sunken temples, even at the beginning of treatment. The present research aimed to explore facial soft tissue changes during and after orthodontic treatment, as well as the related factors affecting facial soft tissue changes. METHODS: This study used 3dMD stereo photography technology to compare facial soft tissue changes among adult females who received orthodontics. A total of 52 adult females (24 teeth extraction, 28 non-teeth extraction cases) were included and potential correlations between related factors (facial morphology features, the change of occlusal height and dental arch width) were evaluated during different treatment periods. RESULTS: Overall, 3D-negative soft tissue changes of the buccal region moderately correlated with distances of nasion-menton and subnasale-menton (both rs = 0.30, P < 0.05) as well as the ratio of subnasale-menton/right gonion-left gonion (rs = 0.33, P < 0.05) and nasion-menton/right zygomatic point-left zygomatic point (rs = 0.30, P < 0.05). Among the 3D angle measurements, the right chelion-median upper lip point-left chelion angle was found to have a moderate correlation with 3D negative changes of the upper cheilion region (rs = 0.31, P < 0.01). Analysis of occlusal height changes revealed that an increase in the posterior facial height (nasion-gonial distance) may be a risk factor for negative changes in the zygomatic arch area. In addition, a moderate positive correlation between the maxillary first molar width changes and 3D-negative changes of the lower cheek region was found (rs = 0.41, P < 0.05). CONCLUSIONS: After orthodontic treatment, adult females with wide and short faces may be prone to negative soft tissue changes. Changes of posterior facial height and arch width between the first molars were also risk factors for negative changes of facial soft tissues. Extraction is not a major factor producing facial soft tissue changes.

Pathogenetic mechanisms of septic cardiomyopathy.

Sepsis is a serious complication after infection, whose further development may lead to multiple organ dysfunction syndrome and so on. It is an important cause of death in critically ill patients who suffered an infection. Sepsis cardiomyopathy is a common complication that exacerbates the prognosis of patients. At present, though the pathogenesis of sepsis cardiomyopathy is not completely clear, in-depth study of the pathogenesis of sepsis cardiomyopathy and the discovery of its potential therapeutic targets may decrease the mortality of sepsis patients and bring clinical benefits. This article reviews mitochondrial dysfunction, mitophagy, oxidation stress, and other mechanisms in sepsis cardiomyopathy.

Mitochondrial Quality Control in the Maintenance of Cardiovascular Homeostasis: The Roles and Interregulation of UPS, Mitochondrial Dynamics and Mitophagy.

Maintenance of normal function of mitochondria is vital to the fate and health of cardiomyocytes. Mitochondrial quality control (MQC) mechanisms are essential in governing mitochondrial integrity and function. The ubiquitin-proteasome system (UPS), mitochondrial dynamics, and mitophagy are three major components of MQC. With the progress of research, our understanding of MQC mechanisms continues to deepen. Gradually, we realize that the three MQC mechanisms are not independent of each other. To the contrary, there are crosstalk among the mechanisms, which can make them interact with each other and cooperate well, forming a triangle interplay. Briefly, the UPS system can regulate the level of mitochondrial dynamic proteins and mitophagy receptors. In the process of Parkin-dependent mitophagy, the UPS is also widely activated, performing critical roles. Mitochondrial dynamics have a profound influence on mitophagy. In this review, we provide new processes of the three major MQC mechanisms in the background of cardiomyocytes and delve into the relationship between them.

Beta3-Adrenergic Receptor Activation Alleviates Cardiac Dysfunction in Cardiac Hypertrophy by Regulating Oxidative Stress.

BACKGROUND: Excessive myocardial oxidative stress could lead to the congestive heart failure. NADPH oxidase is involved in the pathological process of left ventricular (LV) remodeling and dysfunction. ß3-Adrenergic receptor (AR) could regulate cardiac dysfunction proved by recent researches. The molecular mechanism of ß3-AR regulating oxidative stress, especially NADPH oxidase, remains to be determined. METHODS: Cardiac hypertrophy was constructed by the transverse aortic constriction (TAC) model. ROS and NADPH oxidase subunits expression were assessed after ß3-AR agonist (BRL) or inhibitor (SR) administration in cardiac hypertrophy. Moreover, the cardiac function, fibrosis, heart size, oxidative stress, and cardiomyocytes apoptosis were also detected. RESULTS: ß3-AR activation significantly alleviated cardiac hypertrophy and remodeling in pressure-overloaded mice. ß3-AR stimulation also improved heart function and reduced cardiomyocytes apoptosis, oxidative stress, and fibrosis. Meanwhile, ß3-AR stimulation inhibited superoxide anion production and decreased NADPH oxidase activity. Furthermore, BRL treatment increased the neuronal NOS (nNOS) expression in cardiac hypertrophy. CONCLUSION: ß3-AR stimulation alleviated cardiac dysfunction and reduced cardiomyocytes apoptosis, oxidative stress, and fibrosis by inhibiting NADPH oxidases. In addition, the protective effect of ß3-AR is largely attributed to nNOS activation in cardiac hypertrophy.

Inhibiting miR-205 Alleviates Cardiac Ischemia/Reperfusion Injury by Regulating Oxidative Stress, Mitochondrial Function, and Apoptosis.

BACKGROUND: miR-205 is important for oxidative stress, mitochondrial dysfunction, and apoptosis. The roles of miR-205 in cardiac ischemia/reperfusion (I/R) injury remain unknown. The aim of this research is to reveal whether miR-205 could regulate cardiac I/R injury by focusing upon the oxidative stress, mitochondrial function, and apoptosis. METHODS: Levels of miR-205 and Rnd3 were examined in the hearts with I/R injury. Myocardial infarct size, cardiac function, oxidative stress, mitochondria function, and cardiomyocyte apoptosis were detected in mice with myocardial ischemia/reperfusion (MI/R) injury. The primary neonatal cardiomyocytes underwent hypoxia/reoxygenation (H/R) to simulate MI/R injury. RESULTS: miR-205 levels were significantly elevated in cardiac tissues from I/R in comparison with those from Sham. In comparison with controls, levels of Rnd3 were significantly decreased in the hearts from mice with MI/R injury. Furthermore, inhibiting miR-205 alleviated MI/R-induced apoptosis, reduced infarct size, prevented oxidative stress increase and mitochondrial fragmentation, and improved mitochondrial functional capacity and cardiac function. Consistently, overexpression of miR-205 increased infarct size and promoted apoptosis, oxidative stress, and mitochondrial dysfunction in mice with MI/R injury. In cultured mouse neonatal cardiomyocytes, downregulation of miR-205 reduced oxidative stress in H/R-treated cardiomyocytes. Finally, inhibiting Rnd3 ablated the cardioprotective effects of miR-205 inhibitor in MI/R injury. CONCLUSIONS: We conclude that inhibiting miR-205 reduces infarct size, improves cardiac function, and suppresses oxidative stress, mitochondrial dysfunction, and apoptosis by promoting Rnd3 in MI/R injury. miR-205 inhibitor-induced Rnd3 activation is a valid target to treat MI/R injury.

MiR-22 Inhibition Alleviates Cardiac Dysfunction in Doxorubicin-Induced Cardiomyopathy by Targeting the sirt1/PGC-1α Pathway.

Doxorubicin (DOX) cardiotoxicity is a life-threatening side effect that leads to a poor prognosis in patients receiving chemotherapy. We investigated the role of miR-22 in doxorubicin-induced cardiomyopathy and the underlying mechanism in vivo and in vitro. Specifically, we designed loss-of-function and gain-of-function experiments to identify the role of miR-22 in doxorubicin-induced cardiomyopathy. Our data suggested that inhibiting miR-22 alleviated cardiac fibrosis and cardiac dysfunction induced by doxorubicin. In addition, inhibiting miR-22 mitigated mitochondrial dysfunction through the sirt1/PGC-1α pathway. Knocking out miR-22 enhanced mitochondrial biogenesis, as evidenced by increased PGC-1α, TFAM, and NRF-1 expression in vivo. Furthermore, knocking out miR-22 rescued mitophagy, which was confirmed by increased expression of PINK1 and parkin and by the colocalization of LC3 and mitochondria. These protective effects were abolished by overexpressing miR-22. In conclusion, miR-22 may represent a new target to alleviate cardiac dysfunction in doxorubicin-induced cardiomyopathy and improve prognosis in patients receiving chemotherapy.

Inhibiting miR-22 Alleviates Cardiac Dysfunction by Regulating Sirt1 in Septic Cardiomyopathy.

High morbidity and mortality are the most typical characteristics of septic cardiomyopathy. We aimed to reveal the role of miR-22 in septic cardiomyopathy and to explore the underlying mechanisms. miR-22 cardiac-specific knockout (miR-22cKO) mice and miR-22 cardiac-specific transgenic (miR-22cOE) mice were subjected to a cecal ligation and puncture (CLP) operation, while a sham operation was used in the control group. The echocardiogram results suggested that miR-22cKO CLP mice cardiac dysfunction was alleviated. The serum LDH and CK-MB were reduced in the miR-22cKO CLP mice. As expected, there was reduced apoptosis, increased autophagy and alleviated mitochondrial dysfunction in the miR-22cKO CLP mice, while it had contrary role in the miR-22cOE group. Inhibiting miR-22 promoted autophagy by increasing the LC3II/GAPDH ratio and decreasing the p62 level. Additionally, culturing primary cardiomyocytes with lipopolysaccharide (LPS) simulated sepsis-induced cardiomyopathy in vitro. Inhibiting miR-22 promoted autophagic flux confirmed by an increased LC3II/GAPDH ratio and reduced p62 protein level under bafilomycin A1 conditions. Knocking out miR-22 may exert a cardioprotective effect on sepsis by increasing autophagy and decreasing apoptosis via sirt1. Our results revealed that targeting miR-22 may become a new strategy for septic cardiomyopathy treatment.

Recent advances on the roles of LncRNAs in cardiovascular disease.

Cardiovascular diseases are a main cause of mortality whose prevalence continues to increase worldwide. Long non-coding RNAs (lncRNAs) regulate a variety of biological processes by modifying and regulating transcription of coding genes, directly binding to proteins and even coding proteins themselves. LncRNAs play key roles in the occurrence and development of myocardial infarction, heart failure, myocardial hypertrophy, arrhythmias and other pathological processes that significantly affect the prognosis and survival of patients with cardiovascular diseases. We here review the latest research on lncRNAs in cardiovascular diseases as a basis to formulate future research on prevention and treatment of cardiovascular diseases.

Roles and Clinical Applications of Exosomes in Cardiovascular Disease.

Despite substantial improvements in therapeutic strategies, cardiovascular disease (CVD) is still among the leading causes of mortality and morbidity worldwide. Exosomes, extracellular vesicles with a lipid bilayer membrane of endosomal origin, have been the focus of a large body of research in CVD. Exosomes not only serve as carriers for signal molecules responsible for intercellular and interorgan communication underlying CVD pathophysiology but also are bioactive agents which are partly responsible for the therapeutic effect of stem cell therapy of CVD. We here review recent insights gained into the role of exosomes in apoptosis, hypertrophy, angiogenesis, fibrosis, and inflammation in CVD pathophysiology and progression and the application and mechanisms of exosomes as therapeutic agents for CVD.

LncRNA-TWIST1 Promoted Osteogenic Differentiation Both in PPDLSCs and in HPDLSCs by Inhibiting TWIST1 Expression.

HPDLSCs derived from periodontal ligament tissues contribute to tooth development and tissue regeneration. Exploring the effects of long noncoding RNAs (lncRNAs) in the process of osteogenic differentiation of periodontal ligament stem cells would provide novel therapeutic strategies for tissue regeneration. The expression levels of lncRNA, which significantly changed during osteogenic differentiation, were observed by real-time quantitative PCR (q-PCR). Then, we screened for osteogenic-related lncRNA, which was initially named lncRNA-TWIST1. Moreover, we detected the mRNA expression levels of TWIST1 and osteogenesis-related genes after upregulating and downregulating lncRNA-TWIST1 in PPDLSCs (periodontal mesenchymal stem cells from periodontitis patients) and HPDLSCs (periodontal mesenchymal stem cells from healthy microenvironment), respectively. The osteogenic degree was verified by detecting ALP activity and alizarin red staining. LncRNA-TWIST1 decreased the mRNA levels of TWIST1 and promoted osteogenic differentiation in PPDLSCs, which was confirmed by the increase in osteogenesis-related gene levels (Runx2, ALP, and OCN), the increase in ALP activity, and the formation of more osteogenic nodules. In contrast, downregulating lncRNA-TWIST1 decreased the expression of osteogenesis-related genes, ALP activity, and osteogenic nodules both in PPDLSCs and in HPDLSCs. LncRNA-TWIST1 promoted osteogenic differentiation both in PPDLSCs and in HPDLSCs by inhibiting the TWIST1 expression. LncRNA-TWIST1 may be a novel therapeutic strategy to regenerate dental tissues.

High mobility group box 1 promotes the epithelial-to-mesenchymal transition in prostate cancer PC3 cells via the RAGE/NF-κB signaling pathway.

High mobility group box 1 (HMGB1), a critical damage-associated molecular pattern molecule, has been implicated in several inflammatory diseases and cancer types. The overexpression of HMGB1 protein occurs in prostate cancer, and is closely associated with the proliferation and aggressiveness of tumor cells. However, the underlying mechanisms of HMGB1-induced tumor metastasis in prostate cancer remain unclear. In the present study, it was demonstrated that the expression of HMGB1 was high in prostate cancer samples, particularly in the metastatic tissues. Furthermore, recombinant HMGB1 (rHMGB1) enhanced the invasive and metastatic capabilities of the prostate cancer cells. Molecular phenotype alterations of epithelial-to-mesenchymal transition (EMT) and elevated expression levels of matrix metalloproteinase (MMP)-1, -3 and -10 were observed. In addition, advanced glycosylation end-product specific receptor (RAGE) and its downstream molecule nuclear factor (NF)-κB pathway were activated during rHMGB1-induced metastasis. Silencing RAGE or NF-κB reversed the upregulation of MMP and EMT marker expression levels, thus reducing the migration and invasiveness of tumor cells. Taken together, these results suggest that highly expressed HMGB1 drives EMT and the overexpression of MMP-1, -3, -10 via the RAGE/NF-κB signaling pathways, which facilitates the metastasis of prostate cancer and may be a potential therapeutic target for metastatic prostate cancer.

Tissue distribution and excretion of resveratrol in rat after oral administration of Polygonum cuspidatum extract (PCE).

PURPOSE: Polygonum cuspidatum extract as a traditional Chinese medicine is extracted from the dried rhizome and root of Polygonum cuspidatum Sieb.et Zucc. Resveratrol is one of its active components. Studies were performed in rats to define the tissue distribution and excretion of resveratrol in urine and bile, and to characterize (if possible) any metabolites of resveratrol observed in tissues after ig 20mg/kg Polygonum cuspidatum extract. METHOD: For tissue distribution studies, tissues (300 mg) were homogenized and centrifuged with methanol, and metabolites found in selected tissue extract were identified by LC/MS/MS. For urinary and biliary excretion experiments, urine and bile samples were cleaned up by using solid-phase extraction (SPE) with polyamide cartridges. All the concentrations of resveratrol in these biological samples were determined by HPLC with UV detection. RESULT: After a single oral dose of 20mg/kg PCE in rats, resveratrol was mainly distributed in stomach, duodenum, liver and kidney with detectable metabolites resveratrol monoglucuronide and resveratrol monosulfate. The majority of the resveratrol was excreted as metabolites, only 0.59% and 0.027% of the dosage were excreted in urine and bile respectively as unchanged drug within 24h.