Periodontitis in patients with psoriasis: A systematic review and meta-analysis.

OBJECTIVE: The present study aimed to summarize and update the evidence regarding the association between periodontitis and psoriasis. METHODS: The present systematic review was conducted under the guidelines of Transparent Reporting of Systematic Reviews and Meta-Analyses (PRISMA) and was recorded in the PROSPERO database, under registration number CRD42017063799. Three databases (MEDLINE, Embase, and Cochrane Library) were searched up to March 2020. Case-control or cohort studies assessing the association between periodontitis and psoriasis were identified. Quantitative synthesis was conducted with meta-analysis. RESULTS: A total of 13 studies (11 case-control and two cohort studies) assessing the association between periodontitis and psoriasis were included. Of these 13 articles, 9 showed the prevalence of periodontitis or psoriasis. Therefore, meta-analyses were conducted with data retrieved from the nine studies included. Pooled effect estimate for nine studies showed that patients with periodontitis associated with a higher risk of psoriasis with a pooled OR of 2.87 (95% CI, 1.75-4.69). CONCLUSIONS: This systematic review demonstrated a positive association between periodontitis and psoriasis; however, a causal relationship cannot be established. Due to the weak evidence, caution should be taken when interpreting the results regarding periodontal parameters. Well-designed prospective studies are necessary to evaluate interactions between both diseases.

MicroRNA-21 promotes orthodontic tooth movement by modulating the RANKL/OPG balance in T cells.

OBJECTIVES: The present study was designed to investigate the effects of microRNA-21 (miR-21) on orthodontic tooth movement. METHODS: The orthodontic tooth movement model was established in C57BL/6 and miR-21-/- mice with or without implantation of activated T cells. Histological and histomorphometrical analyses were performed by hematoxylin-eosin staining. Tartrate-resistant acid phosphate staining was used to analyze the osteoclast numbers during tooth movement. Enzyme-linked immunosorbent assay, reverse transcription polymerase chain reaction, and immunohistochemistry analysis were used to examine the expression of RANKL and OPG. RESULTS: In miR-21-/- mice, the distance of tooth movement was retarded, the osteoclast number was decreased, and serum RANKL expression was strongly reduced. MiR-21 promoted the secretion of RANKL from activated T cells. Furthermore, activated T cells could partially rescue the decreased orthodontic tooth movement distance in miR-21-/- mice. MiR-21 was shown to promote orthodontic tooth movement by modulating the RANKL/OPG balance in T cells. CONCLUSIONS: The impact of miR-21 on tooth movement was better elucidated, furthering our understanding of its role and clinical applications in orthodontics.

Ecological Balance of Oral Microbiota Is Required to Maintain Oral Mesenchymal Stem Cell Homeostasis.

Oral microbiome is essential for maintenance of oral cavity health. Imbalanced oral microbiome causes periodontal and other diseases. It is unknown whether oral microbiome affect oral stem cells function. This study used a common clinical antibiotic treatment approach to alter oral microbiome ecology and examine whether oral mesenchymal stem cells (MSCs) are affected. We found that altered oral microbiome resulted gingival MSCs deficiency, leading to a delayed wound healing in male mice. Mechanistically, oral microbiome release lipopolysaccharide (LPS) that stimulates the expression of microRNA-21 (miR-21) and then impair the normal function of gingival MSCs and wound healing process through miR-21/Sp1/telomerase reverse transcriptase pathway. This is the first study indicate that interplay between oral microbiome and MSCs homeostasis in male mice. Stem Cells 2018;36:551-561.

MicroRNA-21 promotes wound healing via the Smad7-Smad2/3-Elastin pathway.

Wound healing is regulated by a complex network of cells, molecules, and cytokines, as well as microRNAs (miRNAs). miRNAs were confirmed to influence the wound healing process, and miR-21, an important member of the miRNA family, was also shown to regulate wound healing. The aim of the present study was to investigate the role of miR-21 in the wound healing process and the possible underlying cell signaling pathways. We isolated GMSCs from WT and miR-21-KO mouse gingiva. Flow cytometric analysis and immunocytofluorescense staining were used to identify the GMSCs acquired from WT and miR-21-KO mice. RT-PCR, western blot analysis and immunohistofluorescence staining were performed to examine the expression of extracellular matrix components and key proteins of cell signaling pathways. TargetScan and pmiR-RB-REPORT vectors were used to verify that Smad7 was a direct target of miR-21. Compared to WT mice, miR-21-KO mice showed slower wound healing. RT-PCR and western blot analysis indicated that Elastin expression was downregulated in miR-21-deficient samples. We confirmed that Smad7 was a direct target of miR-21. miR-21 knockout resulted in increased expression of Smad7 and impaired phosphorylation of the Smad2/3 complex. The expression of the Smad7-Smad2/3-Elastin axis in palate tissues sections acquired from WT and miR-21-KO mice showed the same trend. Based on all these results, we demonstrated that miR-21 promoted the wound healing process via the Smad7-Smad2/3-Elastin pathway.

Changes in Event-Related Potentials Underlying Coma Recovery in Patients with Large Left Hemispheric Infarction.

BACKGROUND The aim of this study was to investigate changes in event-related potentials (ERPs) between coma and awakening in patients with large left hemispheric infarction (left LHI). MATERIAL AND METHODS Ten patients with left LHI who suffered coma and survived to awaken were enrolled in this study. The eye-opening subscore of the Glasgow Coma Scale (GCS) was used to assess the extent of patients' arousal. ERPs elicited by the passive oddball paradigm were collected during coma and awakening states, respectively. Peak latencies, peak amplitudes, topography, and time-frequency information of P1, N1, P2, and mismatch negativity (MMN) were compared between the 2 sessions. RESULTS No significant differences in the peak amplitudes and peak latencies of P1 and N1, but significantly greater P2 amplitude with shorter latency in left hemisphere and midline was shown in the awakening state compared with that in coma. A marked shift of P2 topography in response to deviant tones was also seen, from the right centro-parieto-frontal areas during coma to left frontal-midline areas during awakening. MMN waveforms were not detected in 6/10 patients during the coma state, but these 6 patients all recovered to awakening. Evoked oscillations in bilateral hemisphere were profoundly inhibited during the coma state, with poor inter-trial phase synchronization, while obvious activities with broader frequency ranges and consistent inter-trial phase synchronization were observed during awakening state, and different frequency activities were distributed in distinct brain regions. CONCLUSIONS P2 may be a central index of coma recovery and a component of the arousal system. Changes in time-frequency information could provide more information during coma recovery, perhaps including some cognitive processing of the sensory stimulus.

Preparation of MgAlFe-LDHs as a deicer corrosion inhibitor to reduce corrosion of chloride ions in deicing salts.

This material consists of a double hydroxide consisting of Mg, Al, Fe in a 9:2:1 M ratios, which was synthesised by hydrothermal method under constant pH conditions. The products were calcined at 500 °C for use as a deicing corrosion inhibitor, which breaks through the problem that the traditional corrosion inhibitor itself doesn't have the capability of deicing. The raw material of Al and Fe was extracted from the red mud by acid leaching. Characterization by XRD, FTIR, BET, XPS, SEM and TEM revealed that the interlaminar structure of the collapsed double-layered hydroxide material after high temperature calcination was regained by adsorbing Cl-. Cl- was filled between the layers of double hydroxide and existed by chemical adsorption. By measuring the freezing point of mixed deicing salt and the ability to melt snow and deicing, the freezing point of the inhibitor was found. When the solution concentration was 40 wt%, the freezing point of the mixed deicing salt reached -27.6 °C. Corrosion inhibitors can reduce the amount of CaCl2 when used in combination with anhydrous CaCl2. In addition, the determination of the corrosion rate of carbon steel and the resistance to salt freezing of concrete has revealed that the corrosion inhibitor can adsorb Cl- and reduce the content of free Cl- at low temperatures. Therefore, corrosion inhibitor plays a significant role in reducing the amount of Cl- used, the corrosion rate of carbon steel, and the salt-freezing resistance of concrete.

Poly(thymine)-CuNPs: Bimodal Methodology for Accurate and Selective Detection of TNT at Sub-PPT Levels.

Accurate, sensitive, and selective detection of explosives is of vital importance in antiterrorism and homeland security. Fluorescence sensors are prevalent for sensitive and fast in-field explosive detection but are sometimes compromised by accuracy and stability due to the similar structures of explosives, photobleaching, and complex sample matrixes. Herein, we developed a first bimodal methodology capable of both sensitive in-field fluorescence detection and accurate laboratory mass spectrometric quantification of 2,4,6-trinitrotoluene (TNT) by utilizing the characteristic fluorescent and mass spectrometric response of copper nanoparticles (CuNPs). An excellent selectivity was also realized by involving aptamer recognition. The methodology is capable of detecting TNT at subpart per trillion (PPT) levels, with a detection limit of 0.32 pg mL-1 by inductively coupled plasma mass spectrometry (ICPMS) and 0.17 ng mL-1 by fluorimetry. The signal response was accurate and stable for at least 60 days by ICPMS. Thanks to the biospecificity of the aptamer, this bimodal methodology is potentially applicable to a large panel of explosives.

Alveolar ridge dimensional changes following ridge preservation procedure with novel devices: part 3 - histological analysis in non-human primate model.

OBJECTIVES: This study sought to investigate the histological changes following tooth extraction, ridge preservation and augmentation, using novel devices designed to obturate the oral orifice of extraction sockets (SocketKAP™) and provide structural support for sockets with defective bony walls (SocketKAGE™) in a non-human primate model. MATERIAL AND METHODS: Six Macaca fascicularis were imaged by cone beam computed tomography to register their preoperative alveolar bone. Three teeth were extracted in each animal, yielding intact socket walls and were divided into three intervention groups: unassisted healing negative control (Group A); SocketKAP™ (Group B); filled with anorganic bovine bone mineral (ABBM) + SocketKAP™ (Group C). Three additional teeth were extracted in each animal, followed by surgical resection of the entire buccal alveolar bone and divided into three groups: negative control (Group D); SocketKAP™ + SocketKAGE™ (Group E); ABBM + SocketKAP™ + SocketKAGE™ (Group F). Animals were euthanized after 12 weeks, and treatment sites were examined by histology and histomorphometric analysis. RESULTS: Control sockets with unassisted healing (Groups A and D) underwent severe loss of bone width, height and total area (approximately 40-60% loss). Application of SocketKAP™ in sites with intact walls, as well as SocketKAP™ plus SocketKAGE™ in sites with defective buccal walls lead to higher preservation of alveolar bone height after 12 weeks post-intervention. Addition of ABBM leads to the highest degree of alveolar bone dimensional preservation. Control sites with unassisted healing (Groups A and D), as well as sites treated with extraction socket devices (Groups B and E) without ABBM yielded higher percentage of vital bone, compared with sites filled with ABBM (Groups C and F). No adverse histological responses were noted to SocketKAP™ or SocketKAGE™ devices. CONCLUSIONS: SocketKAP™ + SocketKAGE™ devices proved effective in reducing post-extraction alveolar bone resorption mediating favorable wound healing within sockets. Addition of ABBM was associated with reduced volumetric loss, although the bone fill was characterized by less mature as well as more woven bone.

Genome-wide DNA methylation profile of developing deciduous tooth germ in miniature pigs.

BACKGROUND: DNA methylation is an important epigenetic modification critical to the regulation of gene expression during development. To date, little is known about the role of DNA methylation in tooth development in large animal models. Thus, we carried out a comparative genomic analysis of genome-wide DNA methylation profiles in E50 and E60 tooth germ from miniature pigs using methylated DNA immunoprecipitation-sequencing (MeDIP-seq). RESULTS: We observed different DNA methylation patterns during the different developmental stages of pig tooth germ. A total of 2469 differentially methylated genes were identified. Functional analysis identified several signaling pathways and 104 genes that may be potential key regulators of pig tooth development from E50 to E60. CONCLUSIONS: The present study provided a comprehensive analysis of the global DNA methylation pattern of tooth germ in miniature pigs and identified candidate genes that potentially regulate tooth development from E50 to E60.

Wnt5a promotes inflammatory responses via nuclear factor κB (NF-κB) and mitogen-activated protein kinase (MAPK) pathways in human dental pulp cells.

Wnt5a has been found recently to be involved in inflammation regulation through a mechanism that remains unclear. Immunohistochemical staining of infected human dental pulp and tissue from experimental dental pulpitis in rats showed that Wnt5a levels were increased. In vitro, Wnt5a was increased 8-fold in human dental pulp cells (HDPCs) after TNF-α stimulation compared with control cells. We then investigated the role of Wnt5a in HDPCs. In the presence of TNF-α, Wnt5a further increased the production of cytokines/chemokines, whereas Wnt5a knockdown markedly reduced cytokine/ chemokine production induced by TNF-α. In addition, in HDPCs, Wnt5a efficiently induced cytokine/chemokine expression and, in particular, expression of IL-8 (14.5-fold) and CCL2 (25.5-fold), as assessed by a Luminex assay. The cytokine subsets regulated by Wnt5a overlap partially with those induced by TNF-α. However, no TNF-α and IL-1ß was detected after Wnt5a treatment. We then found that Wnt5a alone and the supernatants of Wnt5a-treated HDPCs significantly increased macrophage migration, which supports a role for Wnt5a in macrophage recruitment and as an inflammatory mediator in human dental pulp inflammation. Finally, Wnt5a participates in dental pulp inflammation in a MAPK-dependent (p38-, JNK-, and ERK-dependent) and NF-κB-dependent manner. Our data suggest that Wnt5a, as an inflammatory mediator that drives the integration of cytokines and chemokines, acts downstream of TNF-α.

Biomass-derived multifunctional nanoscale carbon fibers toward fire warning sensors, supercapacitors and moist-electric generators.

Nowadays, great effort has been devoted to designing biomass-derived nanoscale carbon fibers with controllable fibrous morphology, high conductivity, big specific surface area and multifunctional characteristics. Herein, a green and renewable strategy is performed to prepare the biomass-based nanoscale carbon fibers for fire warning sensor, supercapacitor and moist-electric generator. This preparation strategy thoroughly gets over the dependence of petroleum-based polymeride, and effectually improves the energy storage capacity, sensing sensitivity, humidity power generation efficiency of the obtaining biomass-based carbon nanofibers. Without the introduction of any active components or pseudocapacitive materials, the specific capacitance and energy density for biomass-based nanoscale carbon fibers achieve 143.58 F/g and 19.9 Wh/kg, severally. The biomass-based fire sensor displays excellent fire resistance, stability, and flame sensitivity with a response time of 2 s. Furthermore, the biomass-based moist-electric generator shows high power generation efficiency. The output voltage and current of five series connected and parallel-connected biomass-based moist-electric generators reaches 4.30 V and 43 µA, respectively. Notably, as the number of biomass-based moist-electric generators in series or parallel increases, the overall output voltage and current of the device system have a linear relationship. This work proposes a self-powered fire prediction system based on nanoscale carbon fibers that integrates sensing, power generation, and energy storage functions.

Current developments and opportunities of pluripotent stem cells-based therapies for salivary gland hypofunction.

Salivary gland hypofunction (SGH) caused by systemic disease, drugs, aging, and radiotherapy for head and neck cancer can cause dry mouth, which increases the risk of disorders such as periodontitis, taste disorders, pain and burning sensations in the mouth, dental caries, and dramatically reduces the quality of life of patients. To date, the treatment of SGH is still aimed at relieving patients' clinical symptoms and improving their quality of life, and is not able to repair and regenerate the damaged salivary glands. Pluripotent stem cells (PSCs), including embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), and extended pluripotent stem cells (EPSCs), are an emerging source of cellular therapies that are capable of unlimited proliferation and differentiation into cells of all three germ layers. In recent years, the immunomodulatory and tissue regenerative effects of PSCs, their derived cells, and paracrine products of these cells have received increasing attention and have demonstrated promising therapeutic effects in some preclinical studies targeting SGH. This review outlined the etiologies and available treatments for SGH. The existing efficacy and potential role of PSCs, their derived cells and paracrine products of these cells for SGH are summarized, with a focus on PSC-derived salivary gland stem/progenitor cells (SGS/PCs) and PSC-derived mesenchymal stem cells (MSCs). In this Review, we provide a conceptual outline of our current understanding of PSCs-based therapy and its importance in SGH treatment, which may inform and serve the design of future studies.

Progress and perspectives on cell-free regenerative endodontic therapy.

Although teeth with pulpitis/apical periodontitis are saved after successful endodontic therapy, they are devitalized and susceptible to reinfections and fractures. The development of biology-based approaches for dental pulp regeneration or repair is possible today because of recent advances in tissue engineering and biomaterials. Cell-free regenerative endodontic therapy offers a promising strategy for the treatment of necrotic immature permanent teeth in children and adolescents. However, studies are underway to determine whether this procedure can be applied to mature teeth.

Clinical Outcomes Following Immediate Loading of Single-Tooth Implants in the Esthetic Zone: A Systematic Review and Meta-Analysis.

PURPOSE: To identify whether or not immediate loading yields different clinical outcomes from conventional loading of single-tooth implants in the esthetic zone. MATERIALS AND METHODS: Various databases (MEDLINE/PubMed, Cochrane [CENTRAL], and Embase) were searched electronically to find articles published in the English language from January 2000 to April 2018. Only randomized controlled clinical trials (RCTs) that compared conventional and immediate implant loading with a minimum follow-up period of 1 year or more were considered. Available data were pooled for meta-analysis using the Review Manager software. RESULTS: Seven RCTs were included. There was no significant difference between immediate and conventional loading protocols on implant survival at the 1-year follow-up (risk ratio [RR] = 0.99; 95% confidence interval [CI]: 0.95 to 1.02). The differences regarding marginal bone loss between the two protocols were statistically insignificant (mean difference [MD] = 0.03 mm; 95% CI: -0.09 to 0.15 mm at the 1-year follow-up, and MD = -0.01 mm; 95% CI: -0.16 to 0.15 mm at the 2-year follow-up). Soft tissue changes following different loading protocols revealed no significant differences in the mesial papillae (MD = 0.30 mm; 95% CI: -0.25 to 0.85 mm), the distal papillae (MD = -0.00 mm; 95% CI: -0.42 to 0.42 mm), and the midfacial mucosa (MD = -0.33 mm; 95% CI: -1.17 to 0.50 mm) at the 1-year follow-up. The esthetic outcomes and patient satisfaction were reported in two and three RCTs, respectively. CONCLUSION: A short-term follow-up of single-tooth implants in the esthetic zone showed that the loading protocols (conventional or immediate loading) are not likely to influence the clinical outcomes, including implant survival and peri-implant stability of soft and hard tissues.

Balanced oral pathogenic bacteria and probiotics promoted wound healing via maintaining mesenchymal stem cell homeostasis.

OBJECTIVES: The homeostasis of oral pathogenic bacteria and probiotics plays a crucial role in maintaining the well-being and healthy status of human host. Our previous study confirmed that imbalanced oral microbiota could impair mesenchymal stem cell (MSC) proliferation capacity and delay wound healing. However, the effects of balanced oral pathogenic bacteria and probiotics on MSCs and wound healing are far from clear. Here, the balance of pathogenic bacteria Porphyromonas gingivalis and probiotics Lactobacillus reuteri extracts was used to investigate whether balanced oral microbiota modulate the physiological functions of MSCs and promote wound healing. METHODS: The effects of balanced pathogenic bacteria P. gingivalis and probiotics L. reuteri extracts on gingival MSCs (GMSCs) were tested using the migration, alkaline phosphatase activity, alizarin red staining, cell counting kit-8, real-time PCR, and western blot assays. To investigate the role of balanced pathogenic bacteria P. gingivalis and probiotics L. reuteri extracts in the wound of mice, the wounds were established in the mucosa of palate and were inoculated with bacteria every 2 days. RESULTS: We found that the balance between pathogenic bacteria and probiotics enhanced the migration, osteogenic differentiation, and cell proliferation of MSCs. Additionally, local inoculation of the mixture of L. reuteri and P. gingivalis promoted the process of wound healing in mice. Mechanistically, we found that LPS in P. gingivalis could activate NLRP3 inflammasome and inhibit function of MSCs, thereby accelerating MSC dysfunction and delaying wound healing. Furthermore, we also found that reuterin was the effective ingredient in L. reuteri which maintained the balance of pathogenic bacteria and probiotics by neutralizing LPS in P. gingivalis, thus inhibiting inflammation and promoting wound healing. CONCLUSIONS: This study revealed that the homeostasis of oral microbiomes played an indispensable role in maintaining oral heath, provided hopeful methods for the prevention and treatment of oral diseases, and had some referential value for other systemic diseases caused by dysfunction of microbiota and MSCs.

Porphyromonas gingivalis and Lactobacillus rhamnosus GG regulate the Th17/Treg balance in colitis via TLR4 and TLR2.

OBJECTIVES: CD4+ T cells are the key to many immune-inflammatory diseases mediated by microbial disorders, especially inflammatory bowel disease (IBD). The purpose of this study was to explore how pathogenic and probiotic bacteria directly affect the T helper (Th)17 and T regulatory (Treg) cell balance among CD4+ T cells to regulate inflammation. METHODS: Porphyromonas gingivalis (Pg; ATCC 33277) and Lactobacillus rhamnosus GG (LGG; CICC 6141) were selected as representative pathogenic and probiotic bacteria, respectively. Bacterial extracts were obtained via ultrasonication and ultracentrifugation. Flow cytometry, RT-qPCR, ELISAs, immunofluorescence and a Quantibody cytokine array were used. The dextran sodium sulphate (DSS)-induced colitis model was selected for verification. RESULTS: The Pg ultrasonicate induced the apoptosis of CD4+ T cells and upregulated the expression of the Th17-associated transcription factor RoRγt and the production of the proinflammatory cytokines IL-17 and IL-6, but downregulated the expression of the essential Treg transcription factor Foxp3 and the production of the anti-inflammatory factors TGF-ß and IL-10 via the TLR4 pathway. However, LGG extract maintained Th17/Treg homeostasis by decreasing the IL-17+ Th17 proportion and increasing the CD25+ Foxp3+ Treg proportion via the TLR2 pathway. In vivo, Pg-stimulated CD4+ T cells aggravated DSS-induced colitis by increasing the Th17/Treg ratio in the colon and lamina propria lymphocytes (LPLs), and Pg + LGG-stimulated CD4+ T cells relieved colitis by decreasing the Th17/Treg ratio via the JAK-STAT signalling pathway. CONCLUSIONS: Our findings suggest that pathogenic Pg and probiotic LGG can directly regulate the Th17/Treg balance via different TLRs.

Lactobacillus reuteri extracts promoted wound healing via PI3K/AKT/ß-catenin/TGFß1 pathway.

BACKGROUND: The balance of oral microbiomes is crucial to maintain oral health. Microecological imbalance can impair the function of mesenchymal stem cells (MSCs) and lead to delay wound healing. Probiotics is a promising prevention approach for the treatment of oral inflammatory diseases caused by a bacterial infection. However, the effect of probiotics on oral MSCs and wound healing is unclear. In the present study, we used one type of probiotics Lactobacillus reuteri extracts to determine whether bacterial extracts could regulate the functions of gingiva MSCs (GMSCs) and promote wound healing. METHODS: Lactobacillus reuteri was prepared with bacterial extracts using ultrasonic crushing apparatus. The effects of Lactobacillus reuteri extracts on GMSCs were tested using the cell scratch migration, alkaline phosphatase (ALP) activity, alizarin red staining, cell counting kit-8, real-time PCR, and western blot assays. To investigate the role of Lactobacillus reuteri extracts in the wound in mice, the wound position of bilateral mesial gingival of the maxillary first molar was established, the wound area with a size of 1 mm × 2 mm and the full thickness gingiva was removed. Mice with wound were randomly distributed to two groups: injection of 0.9% NaCl (NS group) or injection of 50 µg/ml bacterial extracts. RESULTS: We discovered that 50 µg/ml Lactobacillus reuteri extracts increased the capacities of migration, expression of stem cell markers, osteogenic differentiation, and proliferation of GMSCs. In addition, local injection of 50 µg/ml bacterial extracts could promote wound-healing process in mice models. Mechanistically, we found that Lactobacillus reuteri extracts accelerated the process of wound healing via PI3K/AKT/ß-catenin/TGFß1 pathway. CONCLUSIONS: These data showed that Lactobacillus reuteri extracts could activate the potentials of GMSCs, thus promote wound healing. Our discovery provided the insight of the underlying mechanism activating functions of MSCs and identified Lactobacillus reuteri extracts as a potential therapeutic strategy for accelerating oral wound and potential application in the future dental clinic.

Quantitative proteomic analysis of deciduous molars during cap to bell transition in miniature pig.

Taking advantage of genetic manipulation tools and accessibility, almost all molecular knowledge on vertebrate tooth development was obtained from rodent models that only have one dentition in their entire lives. Whether the tooth development in other vertebrates such as swine or human follows the same rules remains elusive. Rodent dentitions differ considerably from human dentitions, therefore limiting the application of knowledge from rodent tooth to human tooth. Signal-mediated communication between cells and complex gene and protein regulatory networks are key components of tooth development. By combining isobaric tandem mass tag (TMT) labeling with liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) technology, we constructed the proteomic profile of deciduous molars at embryonic days 40 and 50 in miniature pig (Sus scrofa). During the ten days of prenatal development of the miniature pig, the morphology of the lower deciduous molar moves from the early cap to the bell stage. Thus, we identified proteins that are associated with these developing stages and identified differentially regulated proteins (DRPs) that are potential or novel drivers of tooth morphogenesis. Three candidate proteins were validated via qRT-PCR, western blotting analysis, and the location of those proteins in tooth germ were observed by immunohistochemical staining. Multiple signaling pathways and protein interaction network revealed potential mechanisms of early tooth programming in a large mammal. Bioinformatic analysis also showed that cross interaction of Wnt and Sonic hedgehog pathways may play a key role in deciduous development during cap to bell transition in miniature pig. SIGNIFICANCE: We performed the most comprehensive study of the whole tooth germ proteome in mammals to date. The high-throughput proteomic analysis identifies differentially regulated proteins and pathways that will help elucidate the mechanisms of tooth development.

Short-term efficacy and tolerability of venlafaxine extended release in adults with generalized anxiety disorder without depression: A meta-analysis.

BACKGROUND: Although efficacy of venlafaxine extended release (XR) for generalized anxiety disorder (GAD) has been reported in previous analyses in 2002 and 2004, the sample size was rather small and estimate of safety or tolerability was not clear. The present analysis had the advantage of large sample size and provided evidence for tolerability. METHODS: Literature databases were searched, including Pubmed, Embase, Cochrane Central Register of Controlled Trials, Web of science and clinical trials. 10 eligible articles were finally selected and data was extracted and logged into the Review Manager 5.3 by two independent authors. The risk of bias was evaluated by the Cochrane Collaboration's Risk of Bias Tool and the stability of the results was assessed by sensitivity analysis. The publication bias was assessed by funnel plot and Egger's/Begg's test using Stata Version 12.0 software. RESULTS: In the current meta-analysis, 10 articles (14 studies) satisfying the inclusion criteria were analyzed. As efficacy outcomes, our findings indicated venlafaxine XR was significantly more effective than placebo according to mean change of the Hamilton Rating Scale for Anxiety total scores [mean difference = 3.31, 95% confidence interval(CI) 1.44-5.18, P = 0.0005], response [odds ratio(OR) = 1.83, 95%CI 1.58-2.12, P<0.00001], and remission (OR = 2.55, 95%CI 1.36-4.78, P = 0.003). In terms of tolerability, the most frequently reported treatment-emergent adverse events were nausea, dry mouth, dizziness, insomnia, somnolence, and headache. In addition, discontinuation due to all-cause (OR = 1.17, 95%CI 0.92-1.49, P = 0.19) was not significantly different between the two groups, whereas discontinuation due to adverse events was statistically higher in the venlafaxine XR group compared with the placebo treatment (OR = 2.80, 95%CI 2.21-3.54, P<0.00001) and discontinuation due to inefficacy was lower in venlafaxine than placebo treatment (OR = 0.26, 95%CI 0.17-0.40, P<0.00001). There was no significant publication bias and sensitivity analysis showed that our analysis exhibited high stability. CONCLUSION: We concluded that venlafaxine XR (75-225 mg/day) is an effective and well-tolerated pharmacological treatment option for adult patients with GAD.