New strategies against drug resistance to herpes simplex virus Herpes simplex virus(HSV),a member of the Herpesviridae family,is a signi fi cant human pathogen that results in mucocutaneous lesions in the oral cavity or genital infections.Acyclovir(ACV)and related nucleoside analogues can successfully treat HSV infections,but the emergence of drug resistance to ACV has created a barrier for the treatment of HSV infections,especially in immunocompromised patients.There is an urgent need to explore new and effective tactics to circumvent drug resistance to HSV.This review summarises the current strategies in the development of new targets(the DNA helicase/primase(H/P)complex),new types of molecules(nature products)and new antiviral mechanisms(lethal mutagenesis of Janus-type nucleosides)to fi ght the drug resistance of HSV.
Real-time-guided bone regeneration around standardized critical size calvarial defects using bone marrow-derived mesenchymal stem cells and collagen membrane with and without using tricalcium phosphate： an in vivo microcomputed tomographic and histologic experiment in rats The aim of the present real time in vivo micro-computed tomography(m CT)and histologic experiment was to assess the efficacy of guided bone regeneration(GBR)around standardized calvarial critical size defects(CSD)using bone marrow-derived mesenchymal stem cells(BMSCs),and collagen membrane(CM)with and without tricalcium phosphate(TCP)graft material.In the calvaria of nine female Sprague-Dawley rats,full-thickness CSD(diameter 4.6 mm)were created under general anesthesia.Treatment-wise,rats were divided into three groups.In group 1,CSD was covered with a resorbable CM;in group 2,BMSCs were filled in CSD and covered with CM;and in group 3,TCP soaked in BMSCs was placed in CSD and covered with CM.All defects were closed using resorbable sutures.Bone volume and bone mineral density of newly formed bone(NFB)and remaining TCP particles and rate of new bone formation was determined at baseline,2,4,6,and 10 weeks using in vivo m CT.At the 10th week,the rats were killed and calvarial segments were assessed histologically.The results showed that the hardness of NFB was similar to that of the native bone in groups 1 and 2 as compared to the NFB in group 3.Likewise,values for the modulus of elasticity were also significantly higher in group 3 compared to groups 1 and 2.This suggests that TCP when used in combination with BMSCs and without CM was unable to form bone of significant strength that could possibly provide mechanical"lock"between the natural bone and NFB.The use of BMSCs as adjuncts to conventional GBR initiated new bone formation as early as 2 weeks of treatment compared to when GBR is attempted without adjunct BMSC therapy.
The effect of basic fibroblast growth factor on regeneration in a surgical wound model of rat submandibular glands This study developed an animal model of surgically wounded submandibular glands(SMGs)and investigated the effects of collagen gel with basic fibroblast growth factor(b FGF)on tissue regeneration of surgically wounded SMGs in vivo.The animal model was produced by creating a surgical wound using a 3-mm diameter biopsy punch in SMGs.The wound was filled with collagen gel with b FGF(b FGF group)or without b FGF(control group).In the animal model of surgically wounded SMGs,salivary glands without scar tissue around the wound area were observed with smaller areas of collagen gel.Small round and spindle-shape cells invaded the collagen gel in both groups after operation day(AOD)5,and this invasion dramatically increased at AOD 7.Host tissue completely replaced the collagen gel at AOD 21.The invading immune cells in the group treated with collagen gel with b FGF were positive for vimentin,a-smooth muscle actin(a SMA),CD49f,c-kit and AQP5 at AOD 7.Similarly,the m RNA expression of vimentin,a SMA,CD49f,keratin19 and AQP5 was also increased.This study suggests that the use of collagen gels with b FGF improves salivary gland regeneration.
Modification of tooth development by heat shoc protein 60 Although several heat shock proteins have been investigated in relation to tooth development,no available information is available about the spatial and temporal expression pattern of heat shock protein 60(Hsp 60).To characterize Hsp 60 expression in the structures of the developing tooth germ,we used Western blotting,immunohistochemistry and in situ hybridization.Hsp 60 was present in high amounts in the inner and outer enamel epithelia,enamel knot(EK)and stratum intermedium(SI).Hsp 60 also appeared in odontoblasts beginning in the bell stage.To obtain data on the possible effect of Hsp 60 on isolated lower incisors from mice,we performed in vitro culturing.To investigate the effect of exogenous Hsp 60 on the cell cycle during culturing,we used the 5-bromo-2-deoxyuridine(Brd U)incorporation test on dental cells.Exogenously administered Hsp 60 caused bluntness at the apical part of the16.5-day-old tooth germs,but it did not influence the proliferation rate of dental cells.We identified the expression of Hsp 60 in the developing tooth germ,which was present in high concentrations in the inner and outer enamel epithelia,EK,SI and odontoblasts.High concentration of exogenous Hsp 60 can cause abnormal morphology of the tooth germ,but it did not influence the proliferation rate of the dental cells.Our results suggest that increased levels of Hsp 60 may cause abnormalities in the morphological development of the tooth germ and support the data on the significance of Hsp during the developmental processes.
Loss of Ap-nerve endings associated with the Merkel cell-neurite complex in the lesional oral mucosa epithelium of lichen planus and hyperkeratosis The Merkel cell-neurite complex initiates the perception of touch and mediates Ab slowly adapting type I responses.Lichen planus is a chronic inflammatory autoimmune disease with T-cell-mediated inflammation,whereas hyperkeratosis is characterized with or without epithelial dysplasia in the oral mucosa.To determine the effects of lichen planus and hyperkeratosis on the Merkel cell-neurite complex,healthy oral mucosal epithelium and lesional oral mucosal epithelium of lichen planus and hyperkeratosis patients were stained by immunohistochemistry(the avidin-biotin-peroxidase complex and double immunofluorescence methods)using pan cytokeratin,20(K20,a Merkel cell marker),and neurofilament 200(NF200,a myelinated Ab-and Ad-nerve fibre marker)antibodies.NF200-immunoreactive(ir)nerve fibres in healthy tissues and in the lesional oral mucosa epithelium of lichen planus and hyperkeratosis were counted and statistically analysed.In the healthy oral mucosa,K20-positive Merkel cells with and without close association to the intraepithelial NF200-ir nerve fibres were detected.In the lesional oral mucosa of lichen planus and hyperkeratosis patients,extremely rare NF200-ir nerve fibres were detected only in the lamina propria.Compared with healthy tissues,lichen planus and hyperkeratosis tissues had significantly decreased numbers of NF200-ir nerve fibres in the oral mucosal epithelium.Lichen planus and hyperkeratosis were associated with the absence of Ab-nerve endings in the oral mucosal epithelium.Thus,we conclude that mechanosensation mediated by the Merkel cell-neurite complex in the oral mucosal epithelium is impaired in lichen planus and hyperkeratosis.
Calcitonin and vitamin D3 have high therapeutic potentia for improving diabetic mandibular growth The goal of this study was to assess the effect of the intermittent combination of an antiresorptive agent（calcitonin） and an anabolic agent（vitamin D3） on treating the detrimental effects of Type 1 diabetes mellitus（DM） on mandibular bone formation and growth.Forty 3-week-old male Wistar rats were divided into four groups: the control group（normal rats）, the control C+D group（normal rats injected with calcitonin and vitaminD3）, the diabetic C+D group（diabetic rats injected with calcitonin and vitamin D3） and the diabetic group（uncontrolled diabetic rats）. An experimental DM condition was induced in the male Wistar rats in the diabetic and diabetic C+D groups using a single dose of 60 mgkg–1body weight of streptozotocin. Calcitonin and vitamin D3 were simultaneously injected in the rats of the control C+D and diabetic C+D groups. All rats were killed after 4 weeks, and the right mandibles were evaluated by micro-computed tomography and histomorphometric analysis. Diabetic rats showed a significant deterioration in bone quality and bone formation（diabetic group）. By contrast, with the injection of calcitonin and vitamin D3, both bone parameters and bone formation significantly improved（diabetic C+D group）（P < 0.05）. These findings suggest that these two hormones might potentially improve various bone properties.
Effects of quaternary ammonium chain length on the antibacterial and remineralizing effects of a calcium phosphate nanocomposite Composites containing nanoparticles of amorphous calcium phosphate(NACP)remineralize tooth lesions and inhibit caries.A recent study synthesized quaternary ammonium methacrylates(QAMs)with chain lengths(CLs)of 3–18 and determined their effects on a bonding agent.This study aimed to incorporate these QAMs into NACP nanocomposites for the first time to simultaneously endow the material with antibacterial and remineralizing capabilities and to investigate the effects of the CL on the mechanical and biofilm properties.Five QAMs were synthesized:DMAPM(CL3),DMAHM(CL6),DMADDM(CL12),DMAHDM(CL16),and DMAODM(CL18).Each QAM was incorporated into a composite containing 20%NACP and 50%glass fillers.A dental plaque microcosm biofilm model was used to evaluate the antibacterial activity.The flexural strength and elastic modulus of nanocomposites with QAMs matched those of a commercial control composite(n 5 6;P.0.1).Increasing the CL from 3 to 16 greatly enhanced the antibacterial activity of the NACP nanocomposite(P,0.05);further increasing the CL to 18 decreased the antibacterial potency.The NACP nanocomposite with a CL of 16 exhibited biofilm metabolic activity and acid production that were 10-fold lesser than those of the control composite.The NACP nanocomposite with a CL of 16 produced 2-log decreases in the colony-forming units(CFU)of total microorganisms,total streptococci,and mutans streptococci.In conclusion,QAMs with CLs of 3–18 were synthesized and incorporated into an NACP nanocomposite for the first time to simultaneously endow the material with antibacterial and remineralization capabilities.Increasing the CL reduced the metabolic activity and acid production of biofilms and caused a 2-log decrease in CFU without compromising the mechanical properties.Nanocomposites exhibiting strong anti-biofilm activity,remineralization effects,and mechanical properties are promising materials for tooth restorations that inhibit caries.
A simple, sensitive and non-destructive technique for characterizing bovine dental enamel erosion： attenuated total reflection Fourier transform infrared spectroscopy Although many techniques are available to assess enamel erosion in vitro, a simple, non-destructive method with suf fi cient sensitivity for quantifying dental erosion is required. This study characterized the bovine dental enamel erosion induced by various acidic beverages in vitro using attenuated total re fl ection Fourier transform infrared（ATR-FTIR） spectroscopy. Deionized water（control） and 10 acidic beverages were selected to study erosion, and the p H and neutralizable acidity were measured.Bovine anterior teeth（110） were polished with up to 1 200-grit silicon carbide paper to produce fl at enamel surfaces, which were then immersed in 20 m L of the beverages for 30 min at 37 °C. The degree of erosion was evaluated using ATR-FTIR spectroscopy and Vickers’ microhardness measurements. The spectra obtained were interpreted in two ways that focused on theν1, ν3phosphate contour: the ratio of the height amplitude of ν3PO4to that of ν3PO4（Method 1） and the shift of the ν3PO4peak to a higher wavenumber（Method 2）. The percentage changes in microhardness after the erosion treatments were primarily affected by the p H of the immersion media. Regression analyses revealed highly signi fi cant correlations between the surface hardness change and the degree of erosion, as detected by ATR-FTIR spectroscopy（Po0.001）. Method 1 was the most sensitive to these changes, followed by surface hardness change measurements and Method 2. This study suggests that ATRFTIR spectroscopy is potentially advantageous over the microhardness test as a simple, non-destructive, sensitive technique for the quanti fi cation of enamel erosion.
Short-term effects of repetitive transcranial magnetic stimulation on sleep bruxism - a pilot study The purpose of this study was to investigate the effects of repetitive transcranial magnetic stimulation(r TMS)on patients with sleep bruxism(SB).Twelve patients with SB were included in an open,single-intervention pilot study.r TMS at 1 Hz and an intensity of80%of the active motor threshold was applied to the‘hot spot’of the masseter muscle representation at the primary motor cortex bilaterally for 20 min per side each day for 5 consecutive days.The jaw-closing muscle electromyographic(EMG)activity during sleep was recorded with a portable EMG recorder at baseline,during r TMS treatment and at follow-up for 5 days.In addition,patients scored their jaw-closing muscle soreness on a 0–10 numerical rating scale(NRS).Data were analysed with analysis of variance.The intensity of the EMG activity was suppressed during and after r TMS compared to the baseline(P 5 0.04;P 5 0.02,respectively).The NRS score of soreness decreased significantly during and after r TMS compared with baseline(P,0.01).These findings indicated a significant inhibition of jaw-closing muscle activity during sleep along with a decrease of muscle soreness.This pilot study raises the possibility of therapeutic benefits from r TMS in patients with bruxism and calls for further and more controlled studies.
[REVIEW]New strategies against drug resistance to herpes simplex virus(Yu-Chen Jiang;Hui Feng;Yu-Chun Lin;Xiu-Rong Guo[3,4])
[ORJGINALARTICLES]Real-time-guided bone regeneration around standardized critical size calvarial defects using bone marrow-derived mesenchymal stem cells and collagen membrane with and without using tricalcium phosphate： an in vivo microcomputed tomographic and histologic experiment in rats(Khalid Al-Hezaimi[1,2];Sundar Ramalingam;Mansour Al-Askar;Aws S ArRejaie;Nasser Nooh;Fawad Jawad;Abdullah Aldahmash;Muhammad Atteya;Cun-Yu Wang)
The effect of basic fibroblast growth factor on regeneration in a surgical wound model of rat submandibular glands(Fumitaka Kobayashi;Kenichi Matsuzaka;Takashi Inoue)
Modification of tooth development by heat shoc protein 60(Tamas Papp;Angela Polyak;Krisztina Papp;Zoltan Meszar;Roza Zakany;Eva Meszar-Katona;Paine Terdik Tiinde;Chang Hwa Ham[1,2];Szabolcs Felszeghy)
Loss of Ap-nerve endings associated with the Merkel cell-neurite complex in the lesional oral mucosa epithelium of lichen planus and hyperkeratosis(Daniela Calderon Carrion;Yiiksel Korkmaz[1,2,3];Britta Cho;Marion Kopp;Wilhelm Bloch;Klaus Addicks;Wilhelm Niedermeier)
Calcitonin and vitamin D3 have high therapeutic potentia for improving diabetic mandibular growth(Mona A Abbassy[1,2,3];Ippei Watari;Ahmed S Bakry[4,5,6];Takashi Ono;Ali H Hassan)
Effects of quaternary ammonium chain length on the antibacterial and remineralizing effects of a calcium phosphate nanocomposite(Ke Zhang[1,2];Lei Cheng[2,3];Michael D Weir;Yu-Xing Bai;Hockin HK XU[2,4,5])
A simple, sensitive and non-destructive technique for characterizing bovine dental enamel erosion： attenuated total reflection Fourier transform infrared spectroscopy(In-Hye Kim;Jun Sik Son;Bong Ki Min;Young Kyoung Kim;Kyo-Han Kim;Tae-Yub Kwon)
Short-term effects of repetitive transcranial magnetic stimulation on sleep bruxism - a pilot study(Wei-Na Zhou;Hai-Yang Fu;Yi-Fei Du;Jian-Hua Sun;Jing-Lu Zhang;Chen Wang;Peter Svensson;Ke-Lun Wang[1,5])