Herbal medicine and gut microbiota: exploring untapped therapeutic potential in neurodegenerative disease management.

The gut microbiota that exists in the human gastrointestinal tract is incredibly important for the maintenance of general health as it contributes to multiple aspects of host physiology. Recent research has revealed a dynamic connection between the gut microbiota and the central nervous system, that can influence neurodegenerative diseases (NDs). Indeed, imbalances in the gut microbiota, or dysbiosis, play a vital role in the pathogenesis and progression of human diseases, particularly NDs. Herbal medicine has been used for centuries to treat human diseases, including NDs. These compounds help to relieve symptoms and delay the progression of NDs by improving intestinal barrier function, reducing neuroinflammation, and modulating neurotransmitter production. Notably, herbal medicine can mitigate the progression of NDs by regulating the gut microbiota. Therefore, an in-depth understanding of the potential mechanisms by which herbal medicine regulates the gut microbiota in the treatment of NDs can help explain the pathogenesis of NDs from a novel perspective and propose novel therapeutic strategies for NDs. In this review, we investigate the potential neuroprotective effects of herbal medicine, focusing on its ability to regulate the gut microbiota and restore homeostasis. We also highlight the challenges and future research priorities of the integration of herbal medicine and modern medicine. As the global population ages, access to this information is becoming increasingly important for developing effective treatments for these diseases.

Neutrophils are involved in early bone formation during midpalatal expansion.

OBJECTIVE: Midpalatal expansion (MPE) is routinely employed to treat transverse maxillary arch deficiency. Neutrophils are indispensable for recruiting bone marrow stromal cells (BMSCs) at the initial stage of bone regeneration. This study aimed to explore whether neutrophils participate in MPE and how they function during bone formation under mechanical stretching. MATERIALS AND METHODS: The presence and phenotype of neutrophils in the midpalatal suture during expansion were detected by flow cytometry and immunofluorescence staining. The possible mechanism of neutrophil recruitment and polarization was explored in vitro by exposing vascular endothelial cells (VECs) to cyclic tensile strain. RESULTS: The number of neutrophils in the distracted suture peaked on Day 3, and N2-type neutrophils significantly increased on Day 5 after force application. The depletion of circulatory neutrophils reduced bone volume by 43.6% after 7-day expansion. The stretched VECs recruited neutrophils via a CXCR2 mechanism in vitro, which then promoted BMSC osteogenic differentiation through the VEGFA/VEGFR2 axis. Consistently, these neutrophils showed higher expression of canonical N2 phenotype genes, including CD206 and Arg1. CONCLUSIONS: These results suggested that neutrophils participated in early bone formation during MPE. Based on these findings, we propose that stretched VECs recruited and polarized neutrophils, which, in turn, induced BMSC osteogenic differentiation.

Matrix mechanics regulate the polarization state of bone marrow-derived neutrophils through the JAK1/STAT3 signaling pathway.

Matrix mechanics regulate essential cell behaviors through mechanotransduction, and as one of its most important elements, substrate stiffness was reported to regulate cell functions such as viability, communication, migration, and differentiation. Neutrophils (Neus) predominate the early inflammatory response and initiate regeneration. The activation of Neus can be regulated by physical cues; however, the functional alterations of Neus by substrate stiffness remain unknown, which is critical in determining the outcomes of engineered tissue mimics. Herein, a three-dimensional (3D) culture system made of hydrogels was developed to explore the effects of varying stiffnesses (1.5, 2.6, and 5.7 kPa) on the states of Neus. Neus showed better cell integrity and viability in the 3D system. Moreover, it was shown that the stiffer matrix tended to induce Neus toward an anti-inflammatory phenotype (N2) with less adhesion molecule expression, less reactive oxygen species (ROS) production, and more anti-inflammatory cytokine secretion. Additionally, the aortic ring assay indicated that Neus cultured in a stiffer matrix significantly increased vascular sprouting. RNA sequencing showed that a stiffer matrix could significantly activate JAK1/STAT3 signaling in Neus and the inhibition of JAK1 ablated the stiffness-dependent increase in the expression of CD182 (an N2 marker). Taken together, these results demonstrate that a stiffer matrix promotes Neus to shift to the N2 phenotype, which was regulated by JAK1/STAT3 pathway. This study lays the groundwork for further research on fabricating engineered tissue mimics, which may provide more treatment options for ischemic diseases and bone defects. STATEMENT OF SIGNIFICANCE.

Camouflage orthodontic treatment combined with genioplasty distraction osteogenesis for skeletal class II relationship secondary to osteosarcoma excision surgery.

OBJECTIVE: The treatment of orthodontic patients who survive head and neck tumors is challenging because of dentoskeletal deformities and other unexpected dental and facial complications. This case report describes the case of a 26-year-old woman who presented with mandibular retrognathia after survival from osteosarcoma. CLINICAL CONSIDERATIONS: Camouflage orthodontic treatment was chosen instead of combined orthodontic-orthognathic surgery after primary reconstructive surgery with an iliac bone graft. Genioplasty distraction osteogenesis (DO) was performed to achieve an optimal facial profile. Although unexpected condyle dislocation and epithelial hyperplasia occurred during treatment, a favorable facial profile and optimal skeletal and dental relationships were accomplished after 32 months of treatment. CONCLUSIONS: The patient underwent genioplasty DO and experienced unexpected left condyle dislocation. However, the treatment achieved esthetic goals after intermaxillary elastics were applied.

Comparative transcriptome analysis of the cold resistance of the sterile rice line 33S.

Rice (Oryza sativa L.) is one of the most important species for food production worldwide. Low temperature is a major abiotic factor that affects rice germination and reproduction. Here, the underlying regulatory mechanism in seedlings of a TGMS variety (33S) and a cold-sensitive variety (Nipponbare) was investigated by comparative transcriptome. There were 795 differentially expressed genes (DEGs) identified only in cold-treated 33S, suggesting that 33S had a unique cold-resistance system. Functional and enrichment analysis of these DEGs revealed that, in 33S, several metabolic pathways, such as photosynthesis, amino acid metabolism, secondary metabolite biosynthesis, were significantly repressed. Moreover, pathways related to growth and development, including starch and sucrose metabolism, and DNA biosynthesis and damage response/repair, were significantly enhanced. The expression of genes related to nutrient reserve activity were significantly up-regulated in 33S. Finally, three NAC and several ERF transcription factors were predicted to be important in this transcriptional reprogramming. This present work provides valuable information for future investigations of low-temperature response mechanisms and genetic improvement of cold-tolerant rice seedlings.

A cone-beam computed tomographic study evaluating the efficacy of incisor movement with clear aligners: Assessment of incisor pure tipping, controlled tipping, translation, and torque.

INTRODUCTION: This retrospective clinical study aimed to evaluate the efficacy of different types of incisor movements with clear aligners in the sagittal plane. METHODS: Pretreatment and posttreatment cone-beam computed tomography (CBCT) scans were collected from 69 patients who underwent nonextraction treatment with clear aligners (Invisalign; Align Technology, San Jose, Calif). Integrated 3-dimensional models of the virtual incisor position (ClinCheck; Align Technology) and the posttreatment incisor position (from posttreatment CBCT scans) were superimposed over the pretreatment position (from pretreatment CBCT scans) using Mimics software (Materialise, Leuven, Belgium). On the basis of the location of the rotation center, incisors showing pure tipping (>10°), controlled tipping (>10°), translation (>1 mm), or torque (>10°) movements were selected. Efficacy was determined by comparing the predicted and achieved incisor movement, and differences with efficacy were analyzed using Kruskal-Wallis and Shapiro-Wilk tests (α = 0.05). RESULTS: In measurements for 231 incisors, the mean efficacy of incisor movements in the sagittal plane was 55.58%. The most and least predictable movements were pure tipping (72.48%) and torque (35.21%), respectively. Labial root movement was significantly more predictable than lingual root movement, and labial movement of the mandibular incisors was significantly easier than that of the maxillary incisors. The type of tooth movement achieved was different from the type designed. CONCLUSIONS: The efficacy of incisor movement in the sagittal plane using clear aligners varies with designed movement type, and labial root movement appears to be more accurate than the lingual root movement. The biomechanics of clear aligners remains to be further elucidated to achieve more predictable treatment results.

[Protective effect and immune mechanism of berberine on cerebral ischemia/reperfusion injury in rats].

Objective: To investigate the protective effect and immune mechanism of berberine on cerebral ischemia/reperfusion injury in rats. Methods: Fifty SD rats were randomly divided into sham operation group (Sham), model group (Model), berberine low dose groups (BBR-L, 25 mg/kg), berberine medium dose groups (BBR-M, 50 mg/kg) and berberine high dose groups (BBR-H, 100 mg/kg), with 10 rats in each group. Longa suture method was used to establish a rat model of cerebral ischemia/reperfusion, after 2 hours of ischemia, reperfusion for 24 hours. Rats in BBR-L, BBR-M and BBR-H were treated with berbrerine by gavage 2 hours after successful model building, while the sham operation group and the modle group were given the same volume of saline as described above. After 24 hours of administration, the activity of antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), cytokine tumor necrosis factor α (TNF-α) , interferon ß (IFN-ß) , interleukin 6 (IL-6) and nitric oxide (NO) content were detected by ELISA assay. Serum CD4+, CD8+ and CD4+/CD8+ contents were measured by flow cytometry to investigate the immune function of each group. RT-qPCR and Western blot were used to detect NF-kappaB-NOD-like receptors 3 (NF-κB-NLRP3) signal axis key genes and protein expression in rat brain tissue. Results: Compared with the sham operation group, the degree of neurological deficit and the rate of cerebral infarction were increased in the model group (P＜0.05), and the levels of serum NO, TNF-α, IFN-ß, IL-6, NF-κB p65, NLRP3, ASC and caspase-1 in brain tissue were increased (P＜0.05), while the activities of SOD, GSH-Px and the levels of CD4+, CD8+ and CD4+/CD8+ in serum were decreased (P＜0.05). Compared with the model group, the degree of neurological deficit and the rate of cerebral infarction were increased in the BBR-H, BBR-M and BBR-L groups (P＜0.05), and the levels of serum NO, TNF-α, IFN-ß, IL-6, NF-κB p65, NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC) and caspase-1 in brain tissue were increased (P＜0.05), while the activities of SOD, GSH-Px and the levels of CD4+, CD8+ and CD4+/CD8+ in serum were decreased (P＜0.05). Conclusion: Berberine may reduce oxidative stress, inhibit inflammation, enhance immune function, and reduce cerebral ischemia/reperfusion injury in rats, which may be related to the inhibition of NF-κB-NLRP3 signaling.

WGCNA Analysis of Salt-Responsive Core Transcriptome Identifies Novel Hub Genes in Rice.

Rice, being a major staple food crop and sensitive to salinity conditions, bears heavy yield losses due to saline soil. Although some salt responsive genes have been identified in rice, their applications in developing salt tolerant cultivars have resulted in limited achievements. Herein, we used bioinformatic approaches to perform a meta-analysis of three transcriptome datasets from salinity and control conditions in order to reveal novel genes and the molecular pathways underlying rice response to salt. From a total of 28,432 expressed genes, we identify 457 core differentially expressed genes (DEGs) constitutively responding to salt, regardless of the stress duration, genotype, or the tissue. Gene co-expression analysis divided the core DEGs into three different modules, each of them contributing to salt response in a unique metabolic pathway. Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses highlighted key biological processes and metabolic pathways involved in the salt response. We identified important novel hub genes encoding proteins of different families including CAM, DUF630/632, DUF581, CHL27, PP2-13, LEA4-5, and transcription factors, which could be functionally characterized using reverse genetic experiments. This novel repertoire of candidate genes related to salt response in rice will be useful for engineering salt tolerant varieties.

Uncoupling VOR and vestibuloautonomic retention to Coriolis acceleration training in student pilots and control subjects.

PURPOSE: Explore the different vestibular physiologic response retention patterns after Coriolis acceleration training in student pilots and extend the results for use with Chinese astronauts in the future. METHODS: Twelve healthy control male subjects were screened from males familiar with vestibular training and who physically resembled the astronauts. Fourteen student pilots were selected from 23 participants by rotational vestibular function tests. All subjects were exposed to five-day continuous or intermittent Coriolis acceleration training. Subjective motion sickness (MS) symptom scores, electrocardiography, electrogastrography (EGG), post-rotatory nystagmus and renin-angiotensin system responses were measured before, during and after rotational vestibular function tests at different times after vestibular training. RESULTS: Subjects could tolerate 10 min or 15 min of vestibular with mild MS symptoms. Retention of vestibular autonomic responses (retention of MS symptom scores, heart rate variability, power density of EGG, variations in levels of arginine vasopressin) were approximately 1 week for control subjects and approximately 5 weeks for student pilots. Decreases in slow-phase velocity of post-rotatory nystagmus were maintained for 14 weeks for control subjects and 9 weeks for student pilots. CONCLUSIONS: Retention of the vestibulo-autonomic reaction after vestibular training was different for control subjects and student pilots. All parameters related to autonomic responses could be maintained at low levels after vestibular training for approximately 1 week for control subjects and approximately 5 weeks for student pilots. Uncoupling patterns between post-rotatory nystagmus and the vestibulo-autonomic reaction may be helpful in the design of clinical rehabilitation plans for balance-disorder patients and for exploration of artificial gravity in future space missions.

Suppression of miR-16 promotes tumor growth and metastasis through reversely regulating YAP1 in human cholangiocarcinoma.

BACKGROUND & AIMS: Aberrant expression of microRNAs is associated with many cancers progression. Many studies have shown that miR-16 is down-regulated in many cancers. However, its role in cholangiocarcinoma (CCA) is unknown. METHODS: Quantitative real-time PCR (qRT-PCR) was developed to measure miR-16 expression in CCA tissues and cell lines. CCK-8, colony formation and transwell assays were used to reveal the role of miR-16 in CCA cell proliferation and malignant transformation in vitro. The loss-and-gain function was further validated by subcutaneous xenotransplantation and tail vein injection xenotransplantation model in vivo. Dual-luciferase reporter assay was performed to validate the relationship of miR-16 with YAP1. RESULTS: MiR-16 was notably downregulated in CCA tissues, which was associated with tumor size, metastasis, and TNM stage. Both in vitro and in vivo studies demonstrated that miR-16 could suppress proliferation, invasion and metastasis throughout the progression of CCA. We further identified YAP1 as a direct target gene of miR-16 and found that miR-16 could regulate CCA cell growth and invasion in a YAP1-dependent manner. In addition, YAP1 was markedly upregulated in CCA tissues, which was reversely correlated with miR-16 level in tissue samples. Besides, Down-regulation of miR-16 was remarkably associated with tumor progression and poor survival in CCA patients through a Kaplan-Meier survival analysis. CONCLUSIONS: miR-16, as a novel tumor suppressor in CCA through directly targeting YAP1, might be a promising therapeutic target or prognosis biomarker for CCA.

[The impact of personality traits on adolescents' adaptation and compliance to clear retainers].

PURPOSE: The aim of this study was to evaluate the adolescents' adaptation and compliance to clear retainers, and to investigate their associations with personality traits. METHODS: Fifty adolescents at the end of fixed orthodontic treatment were consecutively recruited. After debonding the fixed orthodontic appliances, clear retainers were used. Participants were asked to fill questionnaires 2 months after wearing the clear retainers. A questionnaire was designed to evaluate their adaptation and compliance for clear retianers. Eysenck personality questionnaire was used to assess the personality traits. Spearman rank correlation was used to analyze the associations between personality traits with the adaptation and compliance to clear retainers using SAS8.0 software package. RESULTS: Forty-two of 50 adolescents accomplished the questionnaires. 76% felt no mucous irritation, 95% felt no influence on socializing. However, 75% showed oral constraint, 71% felt impaired speech. Moreover, 40% adolescents wore the retainers less than 18 hours per day. 31% patients had their aligner lost. 83% patients did not brush their teeth after each meal. Neuroticism was positively associated with the effect of impaired chewing (r=0.32). Psychoticism was positively associated with the oral constraint (r=0.31) and facial muscular soreness (r=0.35), but negatively associated with the influence on emotion (r=-0.34). Extraversion was positively associated with the retainers' damage (r=0.31). CONCLUSIONS: Adolescents showed good adaptation for clear retainers, but unsatisfactory compliance. There are associations between adolescents' adaptation and compliance for clear retainers and personality traits. These results suggest that clinicians should pay more attention to the compliance of adolescents when using clear retainer. Personality traits could be a useful prediction to assess the compliance for clear aligners.

Cyclic tensile strain promotes the osteogenic differentiation of a bone marrow stromal cell and vascular endothelial cell co-culture system.

Mechanical stimuli and neovascularization are closely coupled to osteogenic differentiation and new bone formation. The purpose of present study was to detect the effect of cyclic mechanical strain on a co-culture system of bone marrow stromal cells (BMSCs) and vascular endothelial cells (VECs) and to clarify the related mechanisms. Primary BMSCs and VECs were isolated from Sprague-Dawley rats and co-cultured at various ratios (1:0, 1:2, 1:4, 4:1, 2:1, 1:1, and 0:1). To determine optimized loading conditions, the cells were then subjected to various cyclic tensile strains (0%, 3%, 6% and 9%) using a Flexcell 5000 mechanical loading system. A protocol of 6% strain on the co-cultured cells at a 1:1 ratio was selected as the optimized culture conditions based on the best osteogenic effects, which included increased ALP activity, matrix mineralization and the expressions of VEGF, Runx-2 and Col-1. The VEGF-R inhibitor tivozanib was used to analyze the paracrine role of VEGF, and the osteogenesis-promoting effects of 6% tensile strain were abrogated in the co-cultured cells treated with tivozanib. These results demonstrate that cyclic tensile strain promotes osteogenic differentiation in BMSC/VEC co-culture systems, possibly via a VEC-mediated paracrine effect of VEGF on BMSCs.

[The Association Between Serum Uric Acid and Creatinine in Patients with Hypothyroidism].

OBJECTIVE: To determine the relationship between serum uric acid (SUA) and creatinine (SCr) in patients with hypothyroidism. METHODS: A total of 2 078 people who took physical examinations in the West China Hospital, Sichuan University in May 2014 participated in this study. Serum thyrotropin (TSH), free thyroxine (FT4) and free triiodothyronine (FT3) were detected by electrochemiluminescence. SUA was measured using uricase UV method. The participants were divided into three groups according to their thyroid function: hypothyroidism, subclinical hypothyroidism (SCH) and control. The prevalence of hyperuricemia in each group was Estimated. Correlation analyses were performed for the serum indicators. RESULTS: There were 1 685 participants in the control group, 38 in the hypothyroidism group, and 355 in the subclinical hypothyroidism group. Hypothyroidism patients had significantly higher levels of TSH than those in the control and SCH groups. Significant differences in serum levels of FT3 and FT4 were found between the three groups. Higher levels of SCr (P=0. 005) and SUA (P=0. 008) were also found in hypothyroidism patients compared with those in the control and SCH groups. In those younger than 60 years, men were more likely to catch hyperuricemia than women, with 50-59 year old men having the highest prevalence of hyperuricemia. Higher prevalence of hyperuricemia in men (compared to women) was also found in those older than 60 years, but without statistical significance (P=0. 09). After correcting for gender, TSH showed no correlations with SUA (r=-0. 01, P=0. 648) and SCr (r=-0. 02, P=0. 284); FT4 showed negative correlations with SUA (r= -0. 978, P=0. 001) and SCr (r= -0. 599, P= 5. 012); FT3 showed negative correlations with SUA (r= -0. 745, P=0. 007) and SCr (r -0. 457, P=0. 034). CONCLUSION: Reduced thyroid hormone levels may lead to elevated SCr levels. And elevated SCr levels may be issociated with elevated levels of SUA in patients with hypothyroidism.

[Effect of Serum Uric Acid on Renal Function of Patients with Abnormal Glucose Metabolism].

OBJECTIVE: To determine the effect of serum uric acid on renal function of patients with abnormal glucose metabolism. METHODS: A total of 1 495 people who took physical examinations in West China Hospital of Sichuan University in May 2014 were recruited in this study. Serum nitrogen (BUN), creatinine (SCr), triglycerides (TG), cholesterol (TC), high-density lipoprotein (HDL-C), low-density lipoprotein (LDL-C) and uric acid (SUA) of the participants were detected by an automatic biochemical analyzer. The glomerular filtration rate, (eGFR) was calculated with CKD-EPI. According to hyperuriceima (HUA), the participants were divided into groups with impaired fasting glucose (IFG), diabetes (DM), IFG with hyperuicimia, and DM with hyperuricemia. The participants with normal fasting plasma glucose served as controls. Renal dysfunction was detected using eGFR≤50 mL/(min . 1. 73 m2) and SCr≤1. 7 µg/mL. RESULTS: About 13. 18% (197/1 495) participants were identified as IFG with HUA: male (158)/female (39) ratio =4.05; 4.41% (66/1 495) as DM with HUA: male (58)/female (8) ratio = 7. 25. Participants with HUA in the control, IFG and DM groups had higher levels of BUN and SCr and lower levels of eGFR than those without HUA (P<0. 05). HUA was more likely to be associated with serum. lipid in the control and IFG groups (most P<0. 05) than in the DM group (P>0. 05). DM patients without HUA had better renal function and serum lipid levels than those who had HUA in their early stage of abnormal glucose metabolism (IFG with HUA) (P<0. 05). The prevalence of renal dysfunction of IFG patients with HUA was significantly higher than those without HUA, similar to the prevalence of renal dysfunction of DM patients with HIUA (P

[Clinical effect of premolar extraction with high torque self-locking appliances].

PURPOSE: To analyze the clinical effect of extraction correction of patients with maxillary protrusion by using Damon high torque appliances. METHODS: Forty patients with extraction of four first premolars due to orthodontic treatment were selected. They had protrusion of maxilla and were randomly divided into two groups. Both arches of Damon group were treated with Damon high torque appliances and MBT group were corrected with traditional MBT straight wire appliance; patients in two groups received sliding mechanics for adduction of upper anterior teeth. Cephalometric radiophotographs were analyzed before（T0）and after adduction of upper anterior teeth（T1）. The difference between the two groups was analyzed with SPSS15.0 software package. RESULTS: The upper incisors showed a more retruded position in the two groups at T1,although they showed a similar amount in both groups. The backward movement of upper lip was 2.31mm in Damon group, which was significantly less than that of 2.81mm in MBT group(P<0.05). No significant difference in the first molar mesialization was detected between Damon group(2.33 mm) and MBT group(2.36mm) (P>0.05). For anterior teeth retraction, nasolabial angle (NLA) in MBT and Damon group were 107.44°and 106.33°, increase of NLA in MBT group was 9.17°,which was significantly larger than that of 7.22°in Damon group (P<0.05). U1-MxP in MBT and Damon were 110.61°and 114.11°. U1-MxP decreased 12.06°in MBT group, while significant change was deteced in Damon group of 7.61°(P<0.05). CONCLUSIONS: Application of Damon high torque appliances in extraction treatment of maxillary protrusion patients yielded better control of the labial crown torque of anterior teeth, and avoided excessive lingual inclination of anterior teeth compared with MBT in adduction of upper anterior teeth.

[A clinical evaluation on the stability of orthodontic mini-implants using resonance frequency analysis].

PURPOSE: To evaluate the stability of mini-implant by resonance frequency analysis and to determine the optimal loading timing of orthodontic force. METHODS: Fourteen orthodontic patients who had upper first premolars extraction and needed mini-implants to reinforce the anchorage were enrolled in this study. The patients were divided into 2 groups: delay-loading group and selective-loading group. A joined head mini-implant was inserted in the buccal interradicular area on each side of maxilla for each patient and 28 mini-implants in total were used. Osstell resonance frequency device was used to measure the ISQ (implant stability quotients) value. The measurements were performed immediately after the implant insertion and weekly afterwards until week 16. After the ISQ value was stable, orthodontic force of 150g was loaded on the mini-implants in selective-loading group. The same level of force was applied in delay-loading group at week 12. The data was analyzed by one-way ANOVA and t test using SPSS 19.0 software package. RESULTS: Twenty-three mini-implants were stable during the study. Twelve unloading mini-implants in delay-loading group showed maximal ISQ values immediately after insertion and at week 1 (21.48 ± 5.25). The ISQ values decreased gradually from week 2 to week 5 and reached a plateau after week 6 (11.26 ± 3.36). Eleven mini-implants survived in selective-loading group were then loaded at week 6. There were no significant differences of ISQ values in loading and unloading mini-implants after 6 weeks. The remaining 5 mini-implants were loosing during the first 4 weeks, which showed a significant lower initial ISQ values compared to the successful implants. CONCLUSIONS: The stability of mini-implants decreases 1 week after insertion and maintains after 6 weeks. Orthodontic loading after week 6 has no influence on the stability. Lower initial stability is an important factor for the failure of mini-implants.

MicroRNA-124 inhibits proliferation and induces apoptosis by directly repressing EZH2 in gastric cancer.

MicroRNA-124 (miR-124), a pivotal member of the p53 network, was found to be down-regulated in multiple types of tumors and further reported as tumor suppressor microRNA. In this study, we found that miR-124 was down-regulated in gastric cancer cell lines and specimens. Restoration of miR-124 expression inhibited the proliferation and colony formation of gastric cancer cells. EZH2 (enhancer of zeste homolog 2), which has been shown to be an important transcription factor involved in the proliferation and metastasis of tumor cells, was here confirmed to be a direct target gene of miR-124. On the other hand, silencing EZH2 also inhibits cell proliferation of gastric cancer cells. Furthermore, the treatment combining miR-124 with 5-fluorouracil (5-FU) significantly showed more efficient anti-tumor effects than single treatment of miR-124 or 5-FU, and over-expression of miR-124 suppresses the tumor growth in vivo. Our study indicate that miR-124 can suppress gastric cancer cell growth by directly targeting the EZH2 gene and sensitize the treatment effect of 5-FU. Therefore, miR-124 shows tumor-suppressive activity and may be a new and useful approach of gastric cancer therapy.

[Osteoclasts and early bone remodeling after orthodontic micro-implant placement].

PURPOSE: To observe the incidence of osteoclasts during early bone remodeling after orthodontic micro-implant placement. METHODS: Twenty New Zealand rabbits were randomly allotted into 4 groups. One micro-implant was implanted proximal to the epiphyseal plate of the tibia. Animals were sacrificed on day 3, 7, 14 and 28 (n=5). The sequence of histological changes around the micro-implants were evaluated by hematoxylin and eosin (HE) staining. Osteoclasts were identified by TRAP staining. The differences of the number of the osteoclasts among each time point were analyzed by one way ANOVA with SPSS 19.0 software package. RESULTS: After 3 days of implantation, a large number of erythrocytes, inflammatory cells, mesenchymal cells and bone debris were seen at the implant bone interfaces. Few osteoclasts were observed. On day 7, granular woven bone was formed and some osteoclasts were found in the Howship's lacunae. New bone formation and mineralization were apparent on day 14. Meanwhile, large amounts of osteoclasts were found in the latticed woven bone. On day 28, woven trabeculae with lamellate structures connected to lamellar bone and fewer osteoclasts were identified. Semi-quantitative analysis showed that the number of the osteoclasts was at peak on day 14. There were significant differences among each time point (P<0.01). CONCLUSIONS: Osteoclast activity is closely related to bone formation and remodeling after micro-implant insertion.