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Degenerative diseases affecting the nervous and skeletal systems affect the health of millions of elderly people. Optineurin (OPTN) has been associated with numerous neurodegenerative diseases and Paget’s disease of bone (PDB), a degenerative bone disease initiated by hyperactive osteoclastogenesis. In this study, we found age-related increase in OPTN and nuclear factor E2-related factor 2 (NRF2) in vivo. At the molecular level, OPTN could directly interact with both NRF2 and its negative regulator Kelch-like ECH-associated protein 1 (KEAP1) for up-regulating antioxidant response. At the cellular level, deletion of OPTN resulted in increased intracellular reactive oxygen species and increased osteoclastogenic potential. At the tissue level, deletion of OPTN resulted in substantially increased oxidative stress derived from leukocytes that further stimulate osteoclastogenesis. Last, curcumin attenuated hyperactive osteoclastogenesis induced by OPTN deficiency in aged mice. Collectively, our findings reveal an OPTN-NRF2 axis maintaining bone homeostasis and suggest that antioxidants have therapeutic potential for PDB.

PPARG (peroxisome proliferator-activated receptors gamma) is a nuclear receptor protein superfamily member, PPARG agonists have been proven to have broad anticancer properties in experimental studies. Associated clinical oncology investigations have been widely conducted, but no good relevant findings have been reported thus far. This might be caused by the limitations of a few cancer types of clinical studies. Simultaneously, screening natural products of PPARG agonists with minimal toxicity and side effects may aid in the clinical translation of PPARG agonists into the field of cancer. To that purpose, we investigated the association between PPARG gene expression and prognosis in 34 TCGA cancers and discovered that high PPARG gene expression was only a significant correlation (p < 0.05) with overall survival and progression-free survival in KIRP and UVM patients. An up-regulated PPARG expression with down-regulated ATP8B3 expression had the best prognosis in KIRP and UVM patients revealed by differential expression analysis, KEGG enrichment analysis, and tumor single-cell sequencing analysis. Flavonoids in yellow tea were demonstrated may both activate PPARG and inhibit the action of ATP8B3 using quantitative structure-activity relationships and molecular docking. As natural PPARG agonists, tea flavonoids are worth additional investigation in the field of clinical cancer research, especially in KIRP and UVM.

To compare the effectiveness of remineralizing agents in the prevention and reversal of white spot lesions (WSLs), which occur during fixed orthodontic treatment, through a systematic review and network meta-analysis. We reviewed controlled randomized clinical trial (RCT) data querying nine databases combined with a manual search (last search date: March 10, 2020). Of 2273 identified studies, 36 RCTs were finally included. After study selection and data extraction, pair-wise and network meta-analyses were performed to analyze the effectiveness of remineralizing agents in the prevention and reversal of WSLs in the short term (≤ 3 months) and long term (> 3 months). The risk of bias was assessed based on the Cochrane guidelines. Statistical heterogeneity, inconsistencies, and cumulative ranking were also evaluated. In terms of WSL prevention, sodium fluoride (NaF) varnish had the highest cumulative ranking for the short-term decalcification index (99.3%); acidulated phosphate fluoride (APF) foam ranked first for long-term incidence (96.9%), followed by difluorosilane (Dfs) varnish and high-concentration fluoride toothpaste (HFT) (79.4% and 77.4%, respectively). In the reversal of WSLs, no significant difference was found among different agents or their combinations for the two available outcomes (short-term integrated fluorescence loss and short-term percentage of fluorescence loss). In the prevention of WSLs, APF foam showed the best remineralizing effectiveness in the long term (after debonding), followed by Dfs varnish and HFT. It is unclear whether remineralizing agents can effectively reverse WSLs based on the existing evidence. APF foam may be recommended as a remineralizing agent for preventing orthodontically induced WSLs. CRD42019116852.

Innate immunity to nucleic acids forms the backbone for anti-viral immunity and several inflammatory diseases. Upon sensing cytosolic viral RNA, retinoic acid-inducible gene-I-like receptors (RLRs) interact with the mitochondrial antiviral signaling protein (MAVS) and activate TANK-binding kinase 1 (TBK1) to induce type I interferon (IFN-I). TRAF3-interacting protein 3 (TRAF3IP3, T3JAM) is essential for T and B cell development. It is also well-expressed by myeloid cells, where its role is unknown. Here we report that TRAF3IP3 suppresses cytosolic poly(I:C), 5’ppp-dsRNA, and vesicular stomatitis virus (VSV) triggers IFN-I expression in overexpression systems and Traf3ip3−/− primary myeloid cells. The mechanism of action is through the interaction of TRAF3IP3 with endogenous TRAF3 and TBK1. This leads to the degradative K48 ubiquitination of TBK1 via its K372 residue in a DTX4-dependent fashion. Mice with myeloid-specific gene deletion of Traf3ip3 have increased RNA virus-triggered IFN-I production and reduced susceptibility to virus. These results identify a function of TRAF3IP3 in the regulation of the host response to cytosolic viral RNA in myeloid cells., RNA viruses can be detected by immune cell pattern recognition receptors, such as RLRs, resulting in MAVS-TBK1-IRF3 signalling and production of antiviral type 1 interferons. Here the authors show that macrophage TRAF3-interacting protein 3 regulates this signalling pathway by interacting with TRAF3 and TBK1 to suppress interferon responses.

Aim To explore the mRNA and pathways related to retinoblastoma (RB) genesis and development. Methods Microarray datasets GSE29683 (human) and GSE29685 (mouse) were downloaded from NCBI GEO database. Homologous genes between the two species were identified using WGCNA, followed by protein-protein interaction (PPI) network construction and gene enrichment analysis. Disease-related miRNAs and pathways were retrieved from miR2Disease database and Comparative Toxicogenomics Database (CTD), respectively. Results A total of 352 homologous genes were identified. Two pathways including "cell cycle" and "pathway in cancer" in CTD and enrichment analysis were identified and seven miRNAs (including hsa-miR-373, hsa-miR-34a, hsa-miR-129, hsa-miR-494, hsa-miR-503, hsa-let-7 and hsa-miR-518c) were associated with RB. miRNAs modulate "cell cycle" and "pathway in cancer" pathways via regulating 13 genes (including CCND1, CDC25C, E2F2, CDKN2D and TGFB2). Conclusion These results suggest that these miRNAs play crucial roles in RB genesis through "cell cycle" and "pathway in cancer" pathways by regulating their targets including CCND1, CDC25C, E2F2 and CDKN2D.

Emerging evidence suggests comprehensive immune profiling represents a highly promising, yet insufficiently tapped approach to identify potentially prognostic signatures for periodontitis. In this report, we agnostically identified a periodontitis-associated inflammatory expression network with multiple biomarkers identified within gingival crevicular fluid samples from study participants by applying principal component analysis. We identified an IL-17–dominated trait that is associated with periodontal disease and is inversely modified by the level of IL-10. IL-10 mitigated chemokine CXCL5 and CXCL1 expressions in IL-17–stimulated peripheral blood monocytic cells and peripheral blood monocytic cell–derived macrophages. Il10-deficient mice presented more bone loss, which was associated with more Il17 and IL-17–mediated chemokine and cytokine expression at the transcriptional levels in comparison with control wild-type mice in both the Porphyromonas gingivalis–induced experimental murine periodontitis and ligature-induced alveolar bone-loss models. The dampening effect of IL-10 on the excessive signaling of IL-17 appeared to be mediated by innate immune cells populations rather than by gingival epithelial cells, which are the major cell target for IL-17 signaling. Additionally, elevated IL-17 response in Il10-deficient mice specifically elicited an M1-skewing macrophage phenotype in the gingiva that was associated with the advanced bone loss in the ligature model. In summary, IL-17 dominated an inflammatory network characteristic of periodontitis, and IL-10 dampens this excessive IL-17–mediated periodontitis trait.

Polydopamine-assisted modification for bone substitute materials has recently shown great application potential in bone tissue engineering due to its excellent biocompatibility and adhesive properties. A scaffold material's impact on osteoclasts is equally as important as its impact on osteoblasts when considering tissue engineering for bone defect repair, as healthy bone regeneration requires an orchestrated coupling between osteoclasts and osteoblasts. How polydopamine-functionalized bone substitute materials modulate the activity of osteoblast lineage cells has been extensively investigated, but much less is known about their impact on osteoclasts. Moreover, most of the polydopamine-functionalized materials would need to additionally load a biomolecule to exert the modulation on osteoclast activity. Herein, we demonstrated that our biomimetic polydopamine-laced hydroxyapatite collagen (PDHC) scaffold material, which does not need to load additional bioactive agent, is sufficiently able to modulate osteoclast activity in vitro. First, PDHC showed an anti-resorptive potential, characterized by decreased osteoclast differentiation and resorption capacity and changes in osteoclasts' transcriptome profile. Next, cAMP response element-binding protein (CREB) activity was found to mediate PDHC's anti-osteoclastogenic effect. Finally, although PDHC altered clastokines expression pattern of osteoclasts, as revealed by transcriptomic and secretomic analysis, osteoclasts' coupling to osteoblasts was not compromised by PDHC. Collectively, this study demonstrated the PDHC material orients osteoclast behavior to an anti-resorptive pattern without compromising osteoclasts' coupling to osteoblasts. Such a feature is favorable for the net increase of bone mass, which endows the PDHC material with great application potential in preclinical/clinical bone defect repair.

Dioscin is a typical saponin with multiple pharmacological activities. The past few years have seen an emerging interest in and growing research on this pleiotropic saponin. Here, we review the emerging pharmacological activities reported recently, with foci on its antitumor, antimicrobial, anti-inflammatory, antioxidative, and tissue-protective properties. The potential use of dioscin in therapies of diverse clinical disorders is also discussed.

The in vivo antibacterial activity of NO-releasing hyperbranched polymers was evaluated against Porphyromonas gingivalis, a key oral pathogen associated with periodontitis, using a murine subcutaneous chamber model. Escalating doses of NO-releasing polymers (1.5, 7.5, and 37.5 mg/kg) were administered into a P. gingivalis-infected chamber once a day for 3 days. Chamber fluids were collected on day 4, with microbiological evaluation indicating a dose-dependent bactericidal action. In particular, NO-releasing polymers at 37.5 mg/kg (1170 μg of NO/kg) achieved complete bacterial eradication (>6-log reduction in bacterial viability), demonstrating greater efficacy than amoxicillin (∼4-log reduction in bacterial viability), a commonly used antibiotic. Time-kill assays further revealed that largest dose (37.5 mg/kg; 1170 μg of NO/kg) resulted in ∼3-log killing of P. gingivalis after only a single dose. Based on these results, the potential clinical utility of NO-releasing hyperbranched polymers appears promising, particularly for oral health applications.

The long noncoding RNA nuclear‐enriched abundant transcript 1 (NEAT1) is reportedly involved in the initiation and progression of cancers of several types. However, the role, expression status, and the detailed mechanism of NEAT1 in retinoblastoma (RB) yet need to be unraveled. We explored the role and the mechanism of NEAT1 activity in RB. Our data show enhanced NEAT1 expression in RB‐affected tissues compared with the corresponding control. Functional experiments reveal that a NEAT1 knockdown in RB cells significantly inhibits proliferation, cycle progression, and facilitates apoptosis and caspase‐3 and ‐9 activities. Besides that, miR‐124 was predicted to be a target of NEAT1 and its reduced expression, as well as the inverse correlation of NEAT1 with miR‐124, was observed in RB‐affected tissues. Further, luciferase and RNA immunoprecipitation (RIP) assays confirmed the interaction between NEAT1 and miR‐124. Rescue experiments confirmed that the inhibition of miR‐124 could reverse the effect of NEAT1 on RB cell proliferation, cycle arrest, apoptosis, and caspase‐3 and ‐9 activities. Thus, NEAT1 promotes RB progression by sponging miR‐124, providing a therapeutic target for RB.

Background: This study evaluates the overall bone thickness (OBT) and cortical bone thickness (CBT) of mandibular symphysis and to determine the optimal sites for the insertion of orthodontic mini-implants.Methods: Cone-beam computed tomography (CBCT) images of 32 patients (18 males, 14 females), including 16 adults and 16 adolescents were included in this study. The sample was further categorized into three facial types: low angle, average angle, and high angle. OBT and CBT were measured at the mandibular symphysis region. All measurements were performed at six different heights (2 mm, 4 mm, 6 mm, 8 mm, 10 mm, and 12 mm from cementoenamel junction [CEJ]) and at seven different angles (0, 10, 20, 30, 40, 50, 60 degrees to the occlusal plane). Results: Neither OBT nor CBT was influenced by age or sex, except for that CBT was significantly thicker in adults than in adolescents. OBT and CBT were significantly thicker in low-angle cases than in average- and high-angle cases. Both OBT and CBT were significantly influenced by insertion locations, insertion heights, insertion angles, and their interactions. CBT and OBT gained the greatest value at the location between two lower central incisors, and became greater with the increase of insertion height and insertion angle. Both recommended and optimal insertion sites were mapped. Conclusions: Mandibular symphysis region was suitable for the placement of orthodontic mini-implants. The optimal insertion site was 6-10 mm apical to CEJ between two lower central incisors with an insertion angle being 0-60 degrees to the occlusal plane.

Purpose: To describe surgical management and establish visual outcomes of open globe injury (OGI) in pediatric patients requiring vitrectomy. Methods: Forty-eight eyes of 48 pediatric patients underwent vitrectomy for OGI with secondary vitreoretinal complications in the eye center of Jilin University were included. Characteristics of patients, details of ocular examination and operation, presenting and final visual acuity were recorded. Results: Presenting visual acuity less than 20/400 was found in 44 eyes (91.7%), which included no light perception (NLP) in four eyes. At last visit, there was no eyes with visual acuity of NLP, and 19 eyes (39.6%) had a vision recovery to 20/400 or better. Mechanisms of injury, intraocular contents prolapse, presence of hyphema, intraocular foreign body, vitreous hemorrhage, retinal detachment, and total time from injury to PPV > 2 weeks were significant predictors of visual prognosis. Logistic regression analysis showed that hyphema was a significant predictive factor for poor visual outcome. Conclusion: Visual acuity was improved in most of the patients with OGI in this study. Hyphema is an important presenting ocular sign in estimating the post-vitrectomy visual outcome for OGI in children. Proper timing of vitrectomy is suggested, and in this study patients may benefit more with early vitrectomy as less proliferative vitreoretinopathy (PVR) was found together with a better visual acuity.

Supplemental material, sj-docx-1-tej-10.1177_2041731421995465 for Application of bioluminescence resonance energy transfer-based cell tracking approach in bone tissue engineering by Lufei Wang, Dong Joon Lee, Han Han, Lixing Zhao, Hiroshi Tsukamoto, Yong-IL Kim, Adele M Musicant, Kshitij Parag-Sharma, Xiangxiang Hu, Henry C Tseng, Jen-Tsan Chi, Zhengyan Wang, Antonio L Amelio and Ching-Chang Ko in Journal of Tissue Engineering

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has caused Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic. Flavonoids derived Chinese patent medicines has outstanding curative effects for the improvement and treatment of COVID-19. There are numerous studies suggesting that flavonoids-rich tea have antiviral effects. However, bioactive compounds from tea flavonoids with anti-COVID-19 effect, and the potential molecular mechanisms are unclear. In this study, we performed a molecular docking of 468 tea flavonoids and its derivatives with main protease (Mpro), angiotensin-converting enzyme 2 (ACE2), RNA dependent RNA polymerase (RdRp), compared with the positive control drugs of each target. The results suggested that ACE2 and RdRp are the main targets inhibited by tea flavonoids.Q3G Isovitexin, and TF would be considered as the potential candidate compounds of RdRp and ACE2. Our study provides a theoretical basis for further drug design of anti-COVID-19.

Tea, a widely consumed beverage, has long been utilized for promoting human health with a close correlation to hyperglycemia. The Tea Metabolome Database (TMDB), the most complete and comprehensive curated collection of tea compounds data containing 1271 identified small molecule compounds from the tea plant (Camellia sinensis), was established previously by our research team. More recently, our studies have found that various tea types possess an antihyperglycemic effect in mice. However, the bioactive ingredients from tea have potential antihyperglycemic activity and their underlying molecular mechanisms remain unclear. In this study, we used a molecular docking approach to investigate the potential interactions between a selected 747 constituents contained in tea and 11 key protein targets of clinical antihyperglycemic drugs. According to our results, the main antihyperglycemic targets of tea composition were consistent with those of the drug rosiglitazone. The screening results showed that GCG, ECG3’Me, TMDB-01443, and CG had great target binding capacity. The results indicated that these chemicals of tea might affect hyperglycemia by acting on protein targets of rosiglitazone.

Objectives This meta-analysis was performed to investigate the associations between single-nucleotide polymorphisms (SNPs) in the TGF- β and Smad3 genes and arthritis. Methods A meta-analysis was performed in STATA 14.0, with publication bias and meta-regression analysis. All types of arthritis were included, and subgroup analyses were performed to interpret variations among different types of arthritis. Results Twenty-two qualified studieswere selected to analyze the pooled accuracy, and 4 SNP sites were involved. The analysis of the TGFB1 SNP rs1800470 showed an association with arthritis in allelic (P = 0.011), homozygous (P = 0.034) and recessive (P = 0.021) genetic models. The analysis of the TGFB1 SNP rs1800471 demonstrated a close association with rheumatoid arthritis (RA) in homozygous (P = 0.000, 95%) and recessive (P = 0.008) models. The analysis of the SMAD3 SNP rs12901499 revealed a close association with osteoarthritis (OA) in the allelic (P = 0.001) model. Conclusion This research showed that genetic variants of the TGF-β pathway impact arthritis. The polymorphisms rs1800470, rs1800471 and rs12901499 were correlated with a higher prevalence of arthritis.

Abnormally increased resorption contributes to bone degenerative diseases such as Paget’s disease of bone (PDB) through unclear mechanisms. Recently, the optineurin (OPTN) gene has been implicated in PDB, and global OPTN knockout mice (Optn−/−) were shown to exhibit increased formation of osteoclasts (osteoclastogenesis). Growing evidence, including our own, has demonstrated that intracellular reactive oxygen species (ROS) stimulated by receptor activator of nuclear factor kappa-B ligand (RANKL) can act as signaling molecules to promote osteoclastogenesis. Here, we report that OPTN interacts with nuclear factor erythroid-derived factor 2-related factor 2 (NRF2), the master regulator of the antioxidant response, defining a pathway through which RANKL-induced ROS could be regulated for osteoclastogenesis. In this study, monocytes from Optn−/− and wild-type (Optn+/+) mice were utilized to differentiate into osteoclasts, and both qRT-PCR and tartrate-resistant acid phosphatase (TRAP) staining showed that the Optn−/− monocytes exhibited enhanced osteoclastogenesis compared to the Optn+/+ cells. CellROX® staining, qRT-PCR, and Western blotting indicated that OPTN deficiency reduced the basal expression of Nrf2, inhibited the expression of NRF2-responsive antioxidants, and increased basal and RANKL-induced intracellular ROS levels, leading to enhanced osteoclastogenesis. Coimmunoprecipitation (co-IP) showed direct interaction, and immunofluorescence staining showed perinuclear colocalization of the OPTN-NRF2 granular structures during differentiation. Finally, curcumin and the other NRF2 activators attenuated the hyperactive osteoclastogenesis induced by OPTN deficiency. Collectively, our findings reveal a novel OPTN-mediated mechanism for regulating the NRF2-mediated antioxidant response in osteoclasts and extend the therapeutic potential of OPTN in the aging process resulting from ROS-triggered oxidative stress, which is associated with PDB and many other degenerative diseases., Bone degeneration: Identifying a damage-limiting protein The protein optineurin is implicated in regulating the breakdown of bone during natural maintenance by a mechanism that may be relevant to understanding and treating degenerative bone diseases. Cells called osteoclasts mediate bone breakdown during natural bone turnover, but excessive breakdown occurs in some bone diseases. Working with cultured mouse cells, researchers in the USA, led by Ching-Chang Ko at Ohio State University, Columbus, and Henry Tseng at Duke University, identified a molecular signaling pathway in which optineurin interacts with a protein called NRF2, which is known as the master regulator of the antioxidant response. This interaction allows optineurin to limit the production of chemicals called reactive oxidative species which stimulate osteoclast generation. The findings suggest that drugs regulating the optineurin signaling pathway may help treat bone degeneration and possibly other degenerative diseases.

A common feature of many acute and chronic oral diseases is microbial-induced inflammation. Innate immune responses are the first line of defense against pathogenic microorganisms and are initiated by pattern recognition receptors (PRRs) that specifically recognize pathogen-associated molecular patterns and danger-associated molecular patterns. The activation of certain PRRs can lead to the assembly of macromolecular oligomers termed inflammasomes, which are responsible for pro-inflammatory cytokine maturation and secretion and thus activate host inflammatory responses. About 10 years ago, the absent in melanoma 2 (AIM2) was independently discovered by four research groups, and among the "canonical" inflammasomes [including AIM2, NLR family pyrin domain (NLRP)1, NLRP3, NLR family apoptosis inhibitory protein (NAIP)/NLR family, caspase activation and recruitment domain (CARD) containing (NLRC)4, and pyrin], AIM2 so far is the only one that simultaneously acts as a cytosolic DNA sensor due to its DNA-binding ability. Undoubtedly, such a double-faceted role gives AIM2 greater mission and more potential in the mediation of innate immune responses. Therefore, AIM2 has garnered much attention from the broad scientific community during its first 10 years of discovery (2009-2019). How the AIM2 inflammasome is related to oral diseases has aroused debate over the past few years and is under active investigation. AIM2 inflammasome may potentially be a key link between oral diseases and innate immunity. In this review, we highlight the current knowledge of the AIM2 inflammasome and its critical role in the pathogenesis of various oral diseases, which might offer future possibilities for disease prevention and targeted therapy utilizing this continued understanding.

Genome-wide association studies (GWAS) have identified Optineurin (OPTN) as genetically linked to Paget's disease of the bone (PDB), a chronic debilitating bone remodeling disorder characterized by localized areas of increased bone resorption and abnormal bone remodeling. However, only ~10% of mouse models with a mutation in Optn develop PDB, thus hindering the mechanistic understanding of the OPTN-PDB axis. Here, we reveal that 100% of aged Optn global knockout (Optn-/-) mice recapitulate the key clinical features observed in PDB patients, including polyostotic osteolytic lesions, mixed-phase lesions, and increased serum levels of alkaline phosphatase (ALP). Differentiation of primary osteoclasts ex vivo revealed that the absence of Optn resulted in an increased osteoclastogenesis. Mechanistically, Optn-deficient osteoclasts displayed a significantly decreased type I interferon (IFN) signature, resulting from both defective production of IFNβ and impaired signaling via the IFNα/βR, which acts as a negative feedback loop for osteoclastogenesis and survival. These data highlight the dual roles of OPTN in the type I IFN response to restrain osteoclast activation and bone resorption, offering a novel therapeutic target for PDB. Therefore, our study describes a novel and essential mouse model for PDB and define a key role for OPTN in osteoclast differentiation.

BackgroundHuman meridian (Jingluo) system was hypothesized by traditional Chinese medicine (TCM) for thousands of years. In this hypothesis, there believed to be twelve formal meridian channels going through respective organs, carrying fluid and energy, and laying thermal effects. Some treatments based on meridians have been proved effective. However, existence of meridians has never been confirmed. The infrared photograph was employed to display the picture to the meridians since 1970. Unfortunately, no satisfactory results have been obtained. We think that only when a certain meridian is activated will there be thermal effect for successful infrared photograph.Methods We selected thirteen types of tea out of the herbs to activate the hypothesized twelve meridians for imagery taking. We collected 42 volunteers to drink teas and take infrared imageries in thirteen days. After every tea was drunk, infrared imageries of the human bodies were taken immediately. The highest temperatures of the fingers, palms, and above the organs were derived from the imageries. The averages and standard deviations of the standardized data of volunteers were calculated. Significances of the temperature difference among the body areas after drinking different teas were evaluated. ResultsWe found that the temperatures of the organs and fingers possibly connected by twelve hypothesized meridians rose together significantly, i.e., the thumbs and lung after white teas, index fingers and colon after blue teas, middle fingers and thymus after dark black teas, ring fingers and gallbladder after red black teas, little fingers and heart after yellow teas. The temperature distribution on the human bodies exhibited twelve patterns following the meridian hypothesis. Infrared imageries showed quite clear shapes of the organs activated by the teas, e.g., heart and kidneys by yellow teas, thymus by dark black teas, lungs and spleen by white teas, gallbladder and thyroid by red black teas, etc. Some high temperature lines also matched the hypothetic meridians. ConclusionsOur work displayed the imageries of the possible meridians for the first time, and proved with data that different foods may activate different organs following the meridian hypothesis, shedding light on a possible new method of targeted drug designs.

Administration of glucocorticoids is an effective strategy for treating many inflammatory and autoimmune diseases. However, glucocorticoid treatment can have adverse effects on bone, leading to glucocorticoid-induced osteoporosis (GIO), the most common form of secondary osteoporosis. Although the pathogenesis of GIO has been studied for decades, over the past ten years the autophagy machinery has been implicated as a novel mechanism. Autophagy in osteoblasts, osteocytes, and osteoclasts plays a critical role in the maintenance of bone homeostasis. Herein, we specifically discuss how osteoblast autophagy responds to glucocorticoids and its role in the development of GIO.

// Na Li 1 , Lufei Wang 2 , Guangyun Tan 3 , Zhiheng Guo 1 , Lei Liu 1 , Ming Yang 4, * and Jin He 1, * 1 Department of Gynecology and Obstetrics, The First Hospital of Jilin University, Changchun, Jilin 130021, PR China 2 Department of Ophthalmology, The Second Hospital of Jilin University, Changchun, Jilin 130022, PR China 3 Department of Immunology, Institute of Translational Medicine of The First Hospital of Jilin University, Changchun, Jilin 130021, PR China 4 Department of Breast Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, PR China * These authors have contributed equally to this work Correspondence to: Ming Yang, email: yangming196701@163.com Jin He, email: jinhe1204@126.com Keywords: MiR-218, ovarian cancer, RUNX2, proliferation, invasion Received: April 07, 2017 Accepted: July 19, 2017 Published: September 16, 2017 ABSTRACT MicroRNA-218 (miR-218) has been implicated in the development and progression of multiple cancers. We investigated the role of miR-218 in ovarian cancer progression. We found that miR-218 expression levels were lower in ovarian cancer tissues and cell lines than in adjacent normal tissues or a normal ovarian cell line.miR-218 levels associated with International Federation of Gynecology and Obstetrics (FIGO) stage and lymph node metastasis. Exogenous expression of miR-218 inhibited cell proliferation, colony formation, migration, and invasion in vitro and suppressed tumor growth in a tumor-bearing nude mouse model. Runt-related transcription factor 2 (RUNX2) was identified as a direct functional target of miR-218, and its expression was inversely correlated with miR-218 expression in ovarian cancer tissues. RUNX2 overexpression rescued the suppressive effect of miR-218 on ovarian cancer cell proliferation, colony formation, migration, and invasion. These findings highlight an important role played bymiR-218 in the regulation of cancer growth and metastasis, in part by repressing RUNX2 , and revealed the potential of miR-218 as a new therapeutic target inovarian cancer.

The in vivo antibacterial activity of NO-releasing hyperbranched polymers was evaluated against Porphyromonas gingivalis, a key oral pathogen associated with periodontitis, using a murine subcutaneous chamber model. Escalating doses of NO-releasing polymers (1.5, 7.5, and 37.5 mg/kg) were administered into P. gingivalis-infected chamber once a day for three days. Chamber fluids were collected on Day 4, with microbiological evaluation indicating a dose-dependent bactericidal action. In particular, NO-releasing polymers at 37.5 mg/kg (1170 μg of NO/kg) achieved complete bacterial eradication (>6-log reduction in bacterial viability), demonstrating greater efficacy than amoxicillin (~4-log reduction in bacterial viability), a commonly used antibiotic. Time-kill assays further revealed that largest dose (37.5 mg/kg; 1170 μg of NO/kg) resulted in ~3-log killing of P. gingivalis after only a single dose. Based on these results, the potential clinical utility of NO-releasing hyperbranched polymers appears promising, particularly for oral health applications.

How the nervous system regulates bone remodeling is an exciting area of emerging research in bone biology. Accumulating evidence suggest that neurotransmitter-mediated inputs from neurons may act directly on osteoclasts. Dopamine is a neurotransmitter that can be released by hypothalamic neurons to regulate bone metabolism through the hypothalamic-pituitary-gonadal axis. Dopamine is also present in sympathetic nerves that penetrate skeletal structures throughout the body. It has been shown that dopamine suppresses osteoclast differentiation via a D2-like receptors (D2R)-dependent manner, but the intracellular secondary signaling pathway has not been elucidated. In this study, we found that cAMP-response element binding protein (CREB) activity responds to dopamine treatment during osteoclastogenesis. Considering the critical role of CREB in osteoclastogenesis, we hypothesize that CREB may be a critical target in dopamine’s regulation of osteoclast differentiation. We confirmed that D2R is also present in RAW cells and activated by dopamine. Binding of dopamine to D2R inhibits the cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signaling pathway which ultimately decreases CREB phosphorylation during osteoclastogenesis. This was also associated with diminished expression of osteoclast markers that are downstream of CREB. Pharmacological activation of adenylate cyclase (to increase cAMP production) and PKA reverses the effect of dopamine on CREB activity and osteoclastogenesis. Therefore, we have identified D2R/cAMP/PKA/CREB as a candidate pathway that mediates dopamine’s inhibition of osteoclast differentiation. These findings will contribute to our understanding of how the nervous and skeletal systems interact to regulate bone remodeling. This will enable future work toward elucidating the role of the nervous system in bone development, repair, aging, and degenerative disease.

Microblogging, also known as Weibo, has currently become the prevalent social networking platform, and its function of disseminating information has been increasingly recognized and valued. One of the main approaches of information communication on Weibo is forwarding activities among users. Therefore, the key interests have focused on the microblogs that are easily recognized and forwarded. Through predicting the possibility of a micro-blog being forwarded among users, it is able to effectively improve the efficiency of information spreading on the Weibo platform. On the basis of Sina Weibo data, this paper intends to study 13 features of Sina Weibo including user and content, so as to conduct machine learning, to establish a feature analysis model, to identify key influence factors on Weibo forwarding, to study the combination of feature attributes for the first time, to explore the correlation among features, then to predict the probability of a micro-blog being forwarded by users. Meanwhile, concerning different features held by different data, different machine learning algorithms are applied in model training, in order to identify the algorithm with the highest prediction accuracy.

Bone loss is caused by occlusal hypofunction and is a serious health concern. This is particularly true of tooth loss, which is common in the elderly. However, the cellular and molecular mechanisms underlying bone loss have yet to be fully elucidated. Sclerostin and Wnt/β-catenin signaling have previously been reported to serve important roles in regulating bone remodeling. Therefore, the present study aimed to investigate the involvement of sclerostin and Wnt/β-catenin signaling in occlusal hypofunction-induced alveolar bone remodeling. The unilateral maxillary molars of 14 male Sprague-Dawley rats were extracted in order to establish a model of occlusal hypofunction. For each rat, the non-extraction side was treated as the control group for comparisons with the extraction side. At 8 weeks after tooth extraction, the rats were sacrificed and alveolar bone specimens were harvested for X-ray radiography, micro-computed tomography (CT) and histological and immunohistochemical examinations. Bone loss and architecture deterioration were observed at the occlusal hypofunction side. The bone mineral density was markedly decreased and the ratio of bone volume to total volume was significantly decreased at the hypofunction side, as compared with the control side (P