Immunomodulatory Mechanism and Potential Application of Dental Pulp-Derived Stem Cells in Immune-Mediated Diseases.

Dental pulp stem cells (DPSCs) are mesenchymal stem cells (MSCs) derived from dental pulp tissue, which have high self-renewal ability and multi-lineage differentiation potential. With the discovery of the immunoregulatory ability of stem cells, DPSCs have attracted much attention because they have similar or even better immunomodulatory effects than MSCs from other sources. DPSCs and their exosomes can exert an immunomodulatory ability by acting on target immune cells to regulate cytokines. DPSCs can also migrate to the lesion site to differentiate into target cells to repair the injured tissue, and play an important role in tissue regeneration. The aim of this review is to summarize the molecular mechanism and target cells of the immunomodulatory effects of DPSCs, and the latest advances in preclinical research in the treatment of various immune-mediated diseases, providing new reflections for their clinical application. DPSCs may be a promising source of stem cells for the treatment of immune-mediated diseases.

Splicing mutations in AMELX and ENAM cause amelogenesis imperfecta.

BACKGROUND: Amelogenesis imperfecta (AI) is a developmental enamel defect affecting the structure of enamel, esthetic appearance, and the tooth masticatory function. Gene mutations are reported to be relevant to AI. However, the mechanism underlying AI caused by different mutations is still unclear. This study aimed to reveal the molecular pathogenesis in AI families with 2 novel pre-mRNA splicing mutations. METHODS: Two Chinese families with AI were recruited. Whole-exome sequencing and Sanger sequencing were performed to identify mutations in candidate genes. Minigene splicing assays were performed to analyze the mutation effects on mRNA splicing alteration. Furthermore, three-dimensional structures of mutant proteins were predicted by AlphaFold2 to evaluate the detrimental effect. RESULTS: The affected enamel in family 1 was thin, rough, and stained, which was diagnosed as hypoplastic-hypomature AI. Genomic analysis revealed a novel splicing mutation (NM_001142.2: c.570 + 1G > A) in the intron 6 of amelogenin (AMELX) gene in family 1, resulting in a partial intron 6 retention effect. The proband in family 2 exhibited a typical hypoplastic AI, and the splicing mutation (NM_031889.2: c.123 + 4 A > G) in the intron 4 of enamelin (ENAM) gene was observed in the proband and her father. This mutation led to exon 4 skipping. The predicted structures showed that there were obvious differences in the mutation proteins compared with wild type, leading to impaired function of mutant proteins. CONCLUSIONS: In this study, we identified two new splicing mutations in AMELX and ENAM genes, which cause hypoplastic-hypomature and hypoplastic AI, respectively. These results expand the spectrum of genes causing AI and broaden our understanding of molecular genetic pathology of enamel formation.

Effects of Structural and Compositional Changes of Nanochloropsis oceania after Enzyme Treatment on EPA-Rich Lipids Extraction.

Improved methods for the extraction of eicosapentaenoic acid (EPA), an essential and economically important polyunsaturated fatty acid, are urgently required. However, lipid extraction rates using food-grade solvents such as ethanol are usually low. To improve the ethanol-based extraction rate, and to elucidate the relevant mechanisms, we used cellulase and laccase to treat powdered Nannochloropsis, one of the most promising microalgal sources of EPA. Cellulase and laccase synergistically increased lipid yields by 69.31% and lipid EPA content by 42.63%, by degrading the amorphous hemicellulose and cellulose, improving crystallinity, and promoting the release and extraction of lysodiacylglyceryltrimethylhomoserine. Scanning electron microscopy showed that cell morphology was substantially altered, with cell-wall rupture, loss of cell boundaries, and the release of intracellular substances. In conclusion, Nannochloropsis lipid yields may be directly linked to cell-wall hemicellulose structure, and enzymatic treatment to alter this may improve lipid yields.

MicroRNA-31 regulates dental epithelial cell proliferation by targeting Satb2.

MicroRNAs (miRNAs) exhibit strong potential clinical application owing to their extensive regulation and flexible delivery properties. MicroRNA-31 (miR-31) is an evolutionarily conserved miRNA expressed during tooth development, and it is highly expressed in mouse incisor epithelium. The specific role of miR-31 in odontogenesis has not been elucidated comprehensively, and the aim of the present study was to investigate its activity. Our results showed that miR-31 suppressed LS8 cell proliferation by inhibiting the cell cycle at the G1/S transition. Mutation of Special AT-rich sequence-binding protein 2 (SATB2) gene is responsible for human SATB2-associated syndrome (SAS), which is often accompanied by dental abnormities. Here, it was identified as a direct target of miR-31 in LS8 cells and a promoter of cell proliferation. The expression and distribution of SATB2 in mouse molars and incisors were explored using immunofluorescence, which showed strong signals in the nuclei of incisor epithelial cells and weak signals in the cytoplasm of molar epithelial cells. Moreover, rescue experiments demonstrated that Satb2 could mitigate the inhibitory effect of miR-31 on cell proliferation by promoting the expression of CDK4. Collectively, our results suggested that miR-31 regulates dental epithelial cell proliferation by targeting Satb2, highlighting the biological importance of miR-31 in odontogenesis.

Intraflagellar transport 88 (IFT88) is crucial for craniofacial development in mice and is a candidate gene for human cleft lip and palate.

Ciliopathies are pleiotropic human diseases resulting from defects of the primary cilium, and these patients often have cleft lip and palate. IFT88 is required for the assembly and function of the primary cilia, which mediate the activity of key developmental signaling pathways. Through whole exome sequencing of a family of three affected siblings with isolated cleft lip and palate, we discovered that they share a novel missense mutation in IFT88 (c.915G > C, p.E305D), suggesting this gene should be considered a candidate for isolated orofacial clefting. In order to evaluate the function of IFT88 in regulating craniofacial development, we generated Wnt1-Cre;Ift88fl/fl mice to eliminate Ift88 specifically in cranial neural crest (CNC) cells. Wnt1-Cre;Ift88fl/flpups died at birth due to severe craniofacial defects including bilateral cleft lip and palate and tongue agenesis, following the loss of the primary cilia in the CNC-derived palatal mesenchyme. Loss of Ift88 also resulted in a decrease in neural crest cell proliferation during early stages of palatogenesis as well as a downregulation of the Shh signaling pathway in the palatal mesenchyme. Importantly, Osr2KI-Cre;Ift88fl/flmice, in which Ift88 is lost specifically in the palatal mesenchyme, exhibit isolated cleft palate. Taken together, our results demonstrate that IFT88 has a highly conserved function within the primary cilia of the CNC-derived mesenchyme in the lip and palate region in mice and is a strong candidate as an orofacial clefting gene in humans.

[Response surface optimization of purification process for pigment from Coreopsis tinctoria by macroporous resins].

To optimize the purification process of pigments from Coreopsis tinctoria with macroporous resins by establishing second regression model with response surface methodology. The experiment showed that XDA-7 resin had the best purification effect for pigments from C. tinctoria. The optimal absorption conditions for pigments from C. tinctoria were determined as follows： concentration of pigments solution 2.7 g•L⁻¹, flow rate 6 mL•min⁻¹, pH 6. Under these conditions, the absorption rate of pigments was up to 94.16%. Optimal desorption conditions were as follows： ethanol concentration 64%, flow rate 5 mL•min⁻¹, elution dosage 4 BV. Under these conditions, pigment desorption rate was as high as 98.72%.

lncRNA expression signatures in periodontitis revealed by microarray: the potential role of lncRNAs in periodontitis pathogenesis.

Periodontitis, a common chronic inflammatory disease of the periodontium, is caused by dental plaque formation induced by microorganisms. Recent studies have demonstrated that lncRNAs play a critical role in the regulation of gene expression and in the pathogenesis of diseases. To demonstrate that periodontitis is associated with lncRNAs, microarray analysis was used to detect differently expressed lncRNAs in chronic periodontitis and adjacent normal tissues. The results of some differently expressed lncRNAs were further confirmed using real-time PCR. A total of 8925 differentially expressed lncRNAs were detected, including 4313 upregulated lncRNAs and 4612 downregulated lncRNAs. Further lncRNA subgroup analysis showed there were 589 enhancer-like lncRNAs, 238 homeobox (HOX) cluster lncRNAs, and 1218 Rinn's lincRNAs, of which 656 lincRNAs were upregulated and 562 lincRNAs were downregulated. Therefore, we confirmed that lncRNAs were differently expressed in chronic periodontitis tissues compared with adjacent normal tissues, indicating that lncRNAs may exert partial or key roles in periodontitis pathogenesis and development. Taken together, this study may provide potential targets for future treatment of periodontitis and novel diagnostic biomarkers for periodontitis.

Anatomic study on mental canal and incisive nerve canal in interforaminal region in Chinese population.

PURPOSE: This study was aimed to detect the positions of mental canal and incisive nerve canal as well as the prolongation of mandibular canal in interforaminal region in Chinese population to supply the reference data of the surgical safe zone in chin for clinicians. MATERIALS AND METHODS: A total of 80 formalin-fixed semi-mandibles of Chinese adult cadavers were dissected, the positions and courses of mental canal and incisive nerve canal as well as the prolongation of mandibular canal in interforaminal region were measured. RESULTS: The mental foramina were present in all cases (100 %), and most of them were located below 2nd premolar (58.75 %). Accessory mental foramina were observed in 5 %. The anterior end of mandibular canal, extending along the course of 7.37 ± 1.10 mm above the lower border of mandible to interforaminal region about 3.54 ± 0.70 mm medial to the mental foramen, most often ended below between the two premolars (73.75 %), where it continued as the incisive nerve canal (100 %) and the mental canal (96.25 %). Mental canal, with the wall formed by compact bone, being 2.60 ± 0.60 mm in diameter and 4.01 ± 1.20 mm in length, opened into mental foramen. Incisive nerve canal, with the wall formed by thin compact bone and/or partly or completely by spongy bone, being 1.76 ± 0.27 mm in diameter and 24.87 ± 2.23 mm in length, extended to the incisor region along the course of 9.53 ± 1.43 mm above the lower border of mandible, and most often ended below the lateral incisor (70.00 %). CONCLUSION: This research recommended for chin operations in Chinese population: the surgical safe zone could be set in the region about over 4 mm anterior to the mental foramen, and over 12 mm above inferior border of mandible for anterior alveolar surgery, or within 9 mm above inferior border of mandible for genioplasty.

[Crosslinking modification of ultra high molecular weight polyethylene during joint arthroplasty].

OBJECTIVE: To explore the optimal condition of crosslinking modification of ultra high molecular weight polyethylene (UHMWPE) by gamma ray irradiation. METHODS: The hip and knee joint samples of UHMWPE were tested with regards to friction and wear performance at different doses of (60)Co radiation and heat treatment. And the optimal condition of crosslinking was determined by wear performance and physicochemical properties. RESULTS: Under the condition of 75 kGy irradiation and 150 °C heat treatment, crosslinked UHMWPE showed the best performance. Acetabular sample wear rate decreased 63.24% and knee sample wear rate decreased 59.95% compared with conventional UHMWPE. The modified material had excellent mechanical properties of impact strength 83 kJ/m², tensile strength 50.32 MPa, yield strength 21.83 MPa and elongation at break 312%. Also the material showed excellent antifatigue and reliable chemical properties. CONCLUSION: The optimal condition of crosslinking modification of UHMWPE is 75 kGy irradiation after 150 °C heat treatment.

A novel method combining VAT photopolymerization and casting for the fabrication of biodegradable Zn-1Mg scaffolds with triply periodic minimal surface.

Zinc alloy porous scaffolds are expected to be the next generation of degradable orthopedic implants attributed to their suitable degradation rate. However, a few studies have thoroughly investigated its applicable preparation method and functionality as an orthopedic implant. This study fabricated Zn-1Mg porous scaffolds with triply periodic minimal surface (TPMS) structure by a novel method combining VAT photopolymerization and casting. As-built porous scaffolds displayed fully connected pore structures with controllable topology. The manufacturability, mechanical properties, corrosion behaviors, biocompatibility, and antimicrobial performance of the bioscaffolds with pore sizes of 650 µm, 800 µm, and 1040 µm were investigated, and then compared and discussed with each other. In simulations, the mechanical behaviors of porous scaffolds exhibited the same tendency as the experiments. In addition, the mechanical properties of porous scaffolds as a function of degradation time were studied through a 90-day immersion experiment, which can provide a new option for analyzing the mechanical properties of porous scaffolds implanted in vivo. The G06 scaffold with lower pore size presented better mechanical properties before and after degradation compared with G10. The G06 scaffold with the pore size of 650 µm revealed good biocompatibility and antibacterial properties, which makes it possible to be one of the candidates for orthopedic implants.

Novel dentin sialophosphoprotein gene frameshift mutations affect dentin mineralization.

OBJECTIVE: This study aimed to identify candidate genes for inheritable dentin defects in three Chinese pedigrees and characterize the property of affected teeth. DESIGN: Clinical and radiological features were recorded for the affected individuals. Genomic DNA obtained from peripheral venous blood or saliva were analyzed by whole-exome sequencing. The density and microhardness of affected dentin was measured. Scanning electron microscopy (SEM) was also performed to obtain the microstructure phenotype. RESULTS: 1) General appearance: the affected dentitions shared yellowish-brown or milky color. Radiographs showed that the pulp cavity and root canals were obliterated in varying degrees or exhibited a pulp aspect in the 'thistle tube'. Some patients exhibited periapical infections without pulpal exposure, and some affected individuals showed shortened, abnormally thin roots accompanied by severe alveolar bone loss. 2) Genomic analysis: three new frameshift mutations (NM_014208.3: c.2833delA, c.2852delGand c.3239delA) were identified in exon 5 of dentin sialophosphoprotein (DSPP) gene, altering dentin phosphoprotein (DPP) as result. In vitro studies showed that the density and microhardness of affected dentin were decreased, the dentinal tubules were sparse and arranged disorderly, and the dentinal-enamel-junction (DEJ) was abnormal. CONCLUSIONS: In this study, we identified three novel frameshift mutations of dentin sialophosphoprotein gene related to inherited dentin defects. These mutations are speculated to cause abnormal coding of dentin phosphoprotein C-terminus, which affect dentin mineralization. These results expand the spectrum of dentin sialophosphoprotein gene mutations causing inheritable dentin defects and broaden our understanding of the biological mechanisms by which dentin forms.

A pH-neutral bioactive glass coated 3D-printed porous Ti6Al4V scaffold with enhanced osseointegration.

Osseointegration is vital for the success of non-degradable implants like those made of titanium alloys. In order to promote osseointegration, implants are made porous, providing space for bone ingrowth. Despite extensive optimization of the pore geometry and porosity, bone ingrowth into implants is still marginal; further modification to promote bone ingrowth as well as osseointegration becomes paramount. In this study, a pH neutral bioactive glass with the composition of 10.8% P2O5-54.2% SiO2-35% CaO (mol%; hereinafter referred to as PSC) was successfully coated on 3D-printed porous Ti6Al4V scaffolds using an in situ sol-gel method. This PSC coating is strongly bonded to the substrate and quickly induces the formation of hydroxyapatite on the scaffold surface upon contact with body fluid. In vitro, the PSC-coated Ti6Al4V scaffolds showed superior biocompatibility, cell proliferation promotion, cell adhesion, osteogenic differentiation and mineralization compared to their bare counterparts, implying better osseointegration. In vivo experiments confirmed this expectation; after being implanted, the coated scaffolds had more bone ingrowth and osseointegration, and consequently, higher push-out strength was achieved, proving the validity of the proposed concept in this study. In conclusion, PSC coating on 3D-printed porous Ti6Al4V scaffolds can improve osteogenesis, bone ingrowth, and osseointegration. Together with the versatility of this in situ sol-gel coating method, titanium alloy implants with better biological performances may be developed for immediate clinical applications.

Improvement of bacterial cellulose production by manipulating the metabolic pathways in which ethanol and sodium citrate involved.

Nowadays, bacterial cellulose has played more and more important role as new biological material for food industry and medical and industrial products based on its unique properties. However, it is still a difficult task to improve the production of bacterial cellulose, especially a large number of byproducts are produced in the metabolic biosynthesis processes. To improve bacterial cellulose production, ethanol and sodium citrate are added into the medium during the fermentation, and the activities of key enzymes and concentration of extracellular metabolites are measured to assess the changes of the metabolic flux of the hexose monophosphate pathway (HMP), the Embden-Meyerhof-Parnas pathway (EMP), and the tricarboxylic acid cycle (TCA). Our results indicate that ethanol functions as energy source for ATP generation at the early stage of the fermentation in the HMP pathway and the supplementation of ethanol significantly reduces glycerol generation (a major byproduct). While in the EMP pathway, sodium citrate plays a key role, and its supplementation results in the byproducts (mainly acetic acid and pyruvic acid) entering the gluconeogenesis pathway for cellulose synthesis. Furthermore, by adding ethanol and sodium citrate, the main byproduct citric acid in the TCA cycle is also reduced significantly. It is concluded that bacterial cellulose production can be improved by increasing energy metabolism and reducing the formation of metabolic byproducts through the metabolic regulations of the bypasses.

Nano-hydroxyapatite/ß-tricalcium phosphate ceramics scaffolds loaded with cationic liposomal ceftazidime: preparation, release characteristics in vitro and inhibition to Staphylococcus aureus biofilms.

In the current study, nano-hydroxyapatite/ß-tricalcium phosphate (HA/ß-TCP) ceramics scaffolds loaded with cationic liposomal ceftazidime (CLCs) prepared by modified reverse phase evaporation method, the investigations of their release characteristics were performed by the dissolution tests, in vitro anti-biofilm activity of the scaffolds was studied by the determination of bacterial susceptibility with ELISA. The mean particle size, zeta potential, pH and entrapment efficiency of the CLCs studied were 161.5 ± 5.37 nm, 60.60 ± 5.24 mV, 6.90 ± 0.07 and 16.57 ± 0.13%, respectively. Electron microscopic images of the samples indicated that the liposomes were well preserved in the scaffolds and that it was the CLCs rather than free ceftazidime releasing from the scaffolds. The minimal inhibitory concentrations (MICs) to Staphylococcus aureus of free ceftazidime and its liposomal formulation were 6.00 µg/mL and the release behaviors of both CLCs and free ceftazidime from scaffolds were based on the dissolution/diffusion processes, Fick's law. These results demonstrated that CLCs could inhibit remarkably the formation of S. aureus biofilm more effectively than free ceftazidime (P < 0.05). The study demonstrated that the HA/ß-TCP ceramic scaffolds was such a material that could sustain release CLCs and maintain the adequate amounts of CLCs to absorb to biofilm. It provided an ideal way to inhibit bacterial biofilms for clinical practices.

Zinc oxide nanoparticles and polyethylene microplastics affect the growth, physiological and biochemical attributes, and Zn accumulation of rice seedlings.

Metal nanoparticles and microplastics are becoming important pollutants in agricultural fields, but there are few studies on the interaction of zinc oxide nanoparticles (ZnONPs) and polyethylene (PE) microplastics with rice seedlings. The two rice cultivars Xiangyaxiangzhan and Yuxiangyouzhan were grown at three ZnONP levels (0 mg L-1, 50 mg L-1, and 500 mg L-1) and three PE levels (0 mg L-1, 250 mg L-1, and 500 mg L-1), and the growth, physiological attributes, and Zn uptake of rice seedlings were measured. Result showed that the ZnONPs and PE treatment effects on the investigated parameters differed between the cultivars, whilst Yuxiangyouzhan produced 6.98% higher in mean total dry biomass than Xiangyaxiangzhan. The mean total dry biomass in Xiangyaxiagnzhan and Yuxiangyouzhan changed by 10.22-30.85% and - 11.74-25.58% under ZnONPs, respectively. The PE treatments reduced growth parameters in Xiangyaxiangzhan, whilst the 250 mg L-1 PE treatment reduced the growth parameter of Yuxiangyouzhan. Besides, the ZnONP treatment had a stronger effect on rice seedling growth than the PE treatment. Furthermore, the ZnONPs modulated the physiological parameter in plant tissue of the two rice varieties. ZnONP treatment lead to the accumulation of Zn in plant tissue and the shoot Zn content was strongly related to shoot cellulose content. Overall, ZnONPs and PE treatments modulated the growth, physiological and biochemical attributes, and Zn uptake of rice seedlings, and the cultivars and dose effects could not be ignored.

Rare compound heterozygous variants of LAMB3 and histological features of enamel and oral mucosa.

Junctional epidermolysis bullosa (JEB) is a group of autosomal recessive disorders characterized by amelogenesis imperfecta (AI) and fragility of the skin and mucous membranes. The purpose of this study was to identify pathogenic gene variants and investigate the phenotypic characteristics of abnormal enamel structure and mucocutaneous lesions in a patient with JEB. Clinical examination of the patient revealed hypoplastic AI, skin lesions, and oral ulcers, whereas her parents were normal. Whole-exome sequencing (WES) and cDNA cloning identified compound heterozygous variants of LAMB3 in the proband: c.125G>C in exon 3, c.1288 + 1G>A in intron 11, and c.1348C>T in exon 12. Among these, c.125G>C was inherited from her father, and the other two variants were inherited from her mother. Functional prediction indicated that the variants might change protein structure and cause disease. Scanning electron microscopy (SEM) examination of the primary and permanent teeth revealed abnormal enamel morphology and microstructures. Hematoxylin-eosin (HE) and immunofluorescence (IF) staining showed significantly abnormal and disorganized epithelial cells in the gingival mucosa. Our results showed that this was a case of intermediate JEB1A (OMIM #226650) with autosomal recessive inheritance. The proband carried rare compound heterozygous variants of LAMB3. Our results broaden the variant spectrum of the LAMB3 gene and JEB cases. Moreover, this is the first study to identify histological malformations of the primary teeth and oral mucosa in LAMB3-related patients.

Modified Medial Collateral Ligament Indentation Technique in Total Knee Arthroplasty with Severe Type II Valgus Deformity.

OBJECTIVE: To explore the feasibility and clinical efficacy of a modified medial collateral ligament indentation technique in total knee arthroplasty (TKA) with severe type II valgus deformity. METHODS: Consecutive patients with Krackow type II valgus deformity >20° who underwent a primary unilateral TKA between May 2008 and June 2017 were studied retrospectively. A medial collateral ligament indentation technique was performed in 20 patients (MCLI group), and 23 patients received the routine lateral structures release technique (LSR group). Radiological parameters, such as the valgus angle (VA), and functional outcomes including the use of constraint implants, Knee Society Score (KSS), Knee Society Function score (KSF), and thickness of the polyethylene insert were compared between the two groups. RESULTS: A total of 43 consecutive patients had a minimum 2-year follow-up. The preoperative VA was comparable between the MCLI (23.5° ± 5.8°) and LSR groups (21.3° ± 3.2°, P = 0.134), as was the postoperative VA (1.1° ± 2.1° and 2.5° ± 3.0°, respectively, P = 0.084). The mean KSS and KSF scores in the MCLI group were 30.2 ± 4.8 and 38.8 ± 4.8, respectively, before surgery, and they increased to 91.3 ± 2.6 and 86.5 ± 2.4 at the last follow-up. The scores in the LSR group were 31.5 ± 7.5 and 36.5 ± 7.8 before surgery and 92.4 ± 3.5 and 88.5 ± 3.6 at the last follow-up. While no statistically significant differences in pre- or postoperative functional scores were found between the two groups, the MCLI group had thinner polyethylene inserts (9.5 ± 1.1 mm vs 12.9 ± 1.5 mm) and less use of constrained condylar inserts (15% vs 69.6%). During follow-up, the MCLI group had fewer complications. CONCLUSION: A modified MCLI technique can achieve good outcomes in TKA with type II valgus deformity of >20°. It can maintain a normal joint line level, reduce the use of constrained condylar knee prostheses, and is a reliable choice for severe genu valgum.

Sexual dimorphism in Odontobutis sinensis brain-pituitary-gonad axis and liver highlighted by histological and transcriptomic approach.

In this study, sexual dimorphism in Chinese dark sleeper (Odontobutis sinensis) brain-pituitary-gonad axis and liver was highlighted by histological and transcriptomic approach. The results showed that there were two significant differences between males and females. Firstly, males grew larger and faster than females. Transcriptomic analysis and qPCR validation indicated that two key growth genes, insulin-like growth factor (igf) and 25-hydroxyvitamin D-1 alpha hydroxylase (cyp27b), were more highly detected in male liver than that in female liver. Secondly, histological analysis displayed that the liver in males showed an obvious ivory fatty phenomenon with more fat vacuoles and lipid droplet aggregation compared to that in females. Transcriptomic analysis indicated that the transcript level of vitellogenin (vtg) in male liver were significantly lower than that in female liver. After 17ß-estradiol (E2) treatment of primary cultured hepatocytes, the vtg mRNA expression was induced significantly, while dihydrotestosterone (DHT) treatment had little effect on it. Generally, this study will provide some ideas for further exploring the mechanism of sexual dimorphism in Odontobutis sinensis.

Interactions between Candida albicans and the resident microbiota.

Candida albicans is a prevalent, opportunistic human fungal pathogen. It usually dwells in the human body as a commensal, however, once in its pathogenic state, it causes diseases ranging from debilitating superficial to life-threatening systemic infections. The switch from harmless colonizer to virulent pathogen is, in most cases, due to perturbation of the fungus-host-microbiota interplay. In this review, we focused on the interactions between C. albicans and the host microbiota in the mouth, gut, blood, and vagina. We also highlighted important future research directions. We expect that the evaluation of these interplays will help better our understanding of the etiology of fungal infections and shed new light on the therapeutic approaches.

KMT2D deficiency disturbs the proliferation and cell cycle activity of dental epithelial cell line (LS8) partially via Wnt signaling.

Lysine methyltransferase 2D (KMT2D), as one of the key histone methyltransferases responsible for histone 3 lysine 4 methylation (H3K4me), has been proved to be the main pathogenic gene of Kabuki syndrome disease. Kabuki patients with KMT2D mutation frequently present various dental abnormalities, including abnormal tooth number and crown morphology. However, the exact function of KMT2D in tooth development remains unclear. In this report, we systematically elucidate the expression pattern of KMT2D in early tooth development and outline the molecular mechanism of KMT2D in dental epithelial cell line. KMT2D and H3K4me mainly expressed in enamel organ and Kmt2d knockdown led to the reduction in cell proliferation activity and cell cycling activity in dental epithelial cell line (LS8). RNA-sequencing (RNA-seq) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis screened out several important pathways affected by Kmt2d knockdown including Wnt signaling. Consistently, Top/Fop assay confirmed the reduction in Wnt signaling activity in Kmt2d knockdown cells. Nuclear translocation of ß-catenin was significantly reduced by Kmt2d knockdown, while lithium chloride (LiCl) partially reversed this phenomenon. Moreover, LiCl partially reversed the decrease in cell proliferation activity and G1 arrest, and the down-regulation of Wnt-related genes in Kmt2d knockdown cells. In summary, the present study uncovered a pivotal role of histone methyltransferase KMT2D in dental epithelium proliferation and cell cycle homeostasis partially through regulating Wnt/ß-catenin signaling. The findings are important for understanding the role of KMT2D and histone methylation in tooth development.