Three-dimensional finite element analysis of the effect of alveolar cleft bone graft on the maxillofacial biomechanical stabilities of unilateral complete cleft lip and palate.

BACKGROUND: The objective is to clarify the effect of alveolar cleft bone graft on maxillofacial biomechanical stabilities, the key areas when bone grafting and in which should be supplemented with bone graft once bone resorption occurred in UCCLP (unilateral complete cleft lip and palate). METHODS: Maxillofacial CAD (computer aided design) models of non-bone graft and full maxilla cleft, full alveolar cleft bone graft, bone graft in other sites of the alveolar cleft were acquired by processing the UCCLP maxillofacial CT data in three-dimensional modeling software. The maxillofacial bone EQV (equivalent) stresses and bone suture EQV strains under occlusal states were obtained in the finite element analysis software. RESULTS: Under corresponding occlusal states, the EQV stresses of maxilla, pterygoid process of sphenoid bone on the corresponding side and anterior alveolar arch on the non-cleft side were higher than other maxillofacial bones, the EQV strains of nasomaxillary, zygomaticomaxillary and pterygomaxillary suture on the corresponding side were higher than other maxillofacial bone sutures. The mean EQV strains of nasal raphe, the maximum EQV stresses of posterior alveolar arch on the non-cleft side, the mean and maximum EQV strains of nasomaxillary suture on the non-cleft side in full alveolar cleft bone graft model were all significantly lower than those in non-bone graft model. The mean EQV stresses of bilateral anterior alveolar arches, the maximum EQV stresses of maxilla and its alveolar arch on the cleft side in the model with bone graft in lower 1/3 of the alveolar cleft were significantly higher than those in full alveolar cleft bone graft model. CONCLUSIONS: For UCCLP, bilateral maxillae, pterygoid processes of sphenoid bones and bilateral nasomaxillary, zygomaticomaxillary, pterygomaxillary sutures, anterior alveolar arch on the non-cleft side are the main occlusal load-bearing structures before and after alveolar cleft bone graft. Alveolar cleft bone graft mainly affects biomechanical stabilities of nasal raphe and posterior alveolar arch, nasomaxillary suture on the non-cleft side. The areas near nasal floor and in the middle of the alveolar cleft are the key sites when bone grafting, and should be supplemented with bone graft when the bone resorbed in these areas.

An eco-friendly extraction and purification method of nuciferine from Folium nelumbinis with p-sulfonatocalix[6]arenes.

INTRODUCTION: Folium nelumbinis is used as vegetable, functional food and herbal medicine in Asia. p-Sulfonatocalix[6]arene (SC6A) is a water-soluble supramolecular macrocycle and has never been applied to the extraction of herbal products. OBJECTIVE: In this study, SC6A-assisted extraction of nuciferine from Folium nelumbinis has been carried out to develop an eco-friendly extraction process with high extraction efficacy and easy operation. METHODS: Single-factor experiments were adopted to obtain the optimal conditions for the SC6A-assisted extraction of nuciferine from Folium nelumbinis, and then nuciferine and SC6A were separated easily by one-step alkalization. The host-guest complexes between nuciferine and SC6A were analyzed by competitive fluorescence titration, DSC, FT-IR and 1 H-NMR. RESULTS: The optimal SC6A/Folium nelumbinis/solution ratio for extraction was 0.4:1:20 (g/g/mL), with a granulometric fraction below 180 µm and an extraction time of 1 h with soaking. The purity and recovery of nuciferine extracted with SC6A were increased 29.24 and 35.73 times compared with extraction with aqueous solution, respectively. Moreover, a good reusability of SC6A in the extraction of nuciferine was demonstrated. Competitive fluorescence titration, DSC, FT-IR and 1 H-NMR characterization indicated that SC6A could form host-guest complexes with nuciferine at a ratio of 1:1. CONCLUSION: The study provided an eco-friendly, safe and effective nuciferine extraction method, which can be used for the development of nutrition supplements containing nuciferine.

How Deviation of Nasal Septum Affects Nasal Appearance in Unilateral Cleft Patients: A Study Using Cone-Beam Computed Tomography.

AIM: To quantitatively evaluate the relationship between nasal appearance and nasal septum deviation in unilateral complete cleft patients using cone-beam computed tomography.Method: Cone-beam computed tomography images of 180 patients with unilateral cleft lip/palate from June 2014 to June 2017 were used in the study. None of the subjects had undergone septoplasty. The data were compared between the 2 groups to elucidate the relationship between nasal appearance and deviated nasal septum in unilateral complete cleft patients. RESULTS: The mean age of a total of 180 patients (126 males and 54 females) was 14.58 years, with a standard deviation of 7.10 years, ranged from 6 years old to 49 years old. Columella nasi symmetry parameters show slight positive significant association with angle of nasal septal deviation on transerve plan (r = 0.250, P < 0.001), TRSD (r = 0.323, P < 0.001) and coronal range of nasal septal deviation (r = 0.294, P < 0.001), and moderate positive significant association with coronal angle about septal deviation (r = 0.404, P < 0.001). CONCLUSIONS: Columella nasi symmetry affected by septal deviation, whereas there is lack of evidence to say symmetry of nasal tip and base affected by septal deviation. The symmetry of nasal tip and alar base are not just determined by nasal septum deviation. The nasal septum deviation show difference in different cleft type.

Systematic insight into the active constituents and mechanism of Guiqi Baizhu for the treatment of gastric cancer.

Traditional Chinese medicine treatment of diseases has been recognized, but the material basis and mechanisms are not clear. In this study, target prediction of the antigastric cancer (GC) effect of Guiqi Baizhu (GQBZP) and the analysis of potential key compounds, key targets, and key pathways for the therapeutic effects against GC were carried out based on the method of network analysis and Kyoto Encyclopedia of Genes and Genomes enrichment. There were 33 proteins shared between GQBZP and GC, and 131 compounds of GQBZP had a high correlation with these proteins, indicating that the PI3K-AKT signaling pathway might play a key role in GC. From these studies, we selected human epidermal growth factor receptor 2 (HER2) and programmed cell death 1-ligand 1 (PD-L1) for docking; the results showed that 385 and 189 compounds had high docking scores with HER2 and PD-L1, respectively. Six compounds were selected for microscale thermophoresis (MST). Daidzein/quercetin and isorhamnetin/formononetin had the highest binding affinity for HER2 and PD-L1, with Kd values of 3.7 µmol/L and 490, 667, and 355 nmol/L, respectively. Molecular dynamics simulation studies based on the docking complex structures as the initial conformation yielded the binding free energy between daidzein/quercetin with HER2 and isorhamnetin/formononetin with PD-L1, calculated by molecular mechanics Poisson-Boltzmann surface area, of -26.55, -14.18, -19.41, and -11.86 kcal/mol, respectively, and were consistent with the MST results. In vitro experiments showed that quercetin, daidzein, and isorhamnetin had potential antiproliferative effects in MKN-45 cells. Enzyme activity assays showed that quercetin could inhibit the activity of HER2 with an IC50 of 570.07 nmol/L. Our study provides a systematic investigation to explain the material basis and molecular mechanism of traditional Chinese medicine in treating diseases.

[Activation of the JAK/STAT signal pathway may be involved in DNA damage of A549 cells induced by X-ray].

The aim of this study was to investigate the relationship between the effects of different doses of X-rays on DNA damage and JAK/STAT signaling pathway activation in A549 cells. The A549 cells were radiated with X-rays at doses of 2, 4, and 8 Gy. The proliferation of A549 cells was detected by CCK8 method. The content of interleukin 6 (IL-6) in culture medium at different time points after irradiation was detected by enzyme-linked immunoassay, and the expression levels of IL-6 receptor (IL-6R) and p53 binding protein 1 (53BP1) were detected by immunofluorescent staining. The expression levels of JAK2, p-JAK2, STAT3 and p-STAT3 were detected by Western blot. The results showed that, compared with the control group, X-ray irradiation reduced the cellular proliferation, up-regulated the expression of 53BP1, increased the IL-6 content in the medium supernatant, and up-regulated the protein expression levels of IL-6R, JAK2, p-JAK2, STAT3, and p-STAT3. The above effects of X-ray irradiation were dose-dependent. These results suggest that the mechanism by which X-rays cause DNA damage in A549 cells may involve activation of the JAK/STAT signaling pathway.

Riboflavin accumulation and molecular characterization of cDNAs encoding bifunctional GTP cyclohydrolase II/3,4-dihydroxy-2-butanone 4-phosphate synthase, lumazine synthase, and riboflavin synthase in different organs of Lycium chinense plant.

Riboflavin (vitamin B2) is the precursor of flavin mononucleotide and flavin adenine dinucleotide-essential cofactors for a wide variety of enzymes involving in numerous metabolic processes. In this study, a partial-length cDNA encoding bifunctional GTP cyclohydrolase II/3,4-dihydroxy-2-butanone-4-phosphate synthase (LcRIBA), 2 full-length cDNAs encoding lumazine synthase (LcLS1 and LcLS2), and a full-length cDNA encoding riboflavin synthase (LcRS) were isolated from Lycium chinense, an important traditional medicinal plant. Sequence analyses showed that these genes exhibited high identities with their orthologous genes as well as having the same common features related to plant riboflavin biosynthetic genes. LcRIBA, like other plant RIBAs, contained a DHBPS region in its N terminus and a GCHII region in its C-terminal part. LcLSs and LcRS carried an N-terminal extension found in plant riboflavin biosynthetic genes unlike the orthologous microbial genes. Quantitative real-time polymerase chain reaction analysis showed that 4 riboflavin biosynthetic genes were constitutively expressed in all organs examined of L. chinense plants with the highest expression levels found in the leaves or red fruits. LcRIBA, which catalyzes 2 initial reactions in riboflavin biosynthetic pathway, was the highest transcript in the leaves, and hence, the richest content of riboflavin was detected in this organ. Our study might provide the basis for investigating the contribution of riboflavin in diverse biological activities of L. chinense and may facilitate the metabolic engineering of vitamin B2 in crop plants.

Molecular characterization of carotenoid biosynthetic genes and carotenoid accumulation in Lycium chinense.

Lycium chinense is a shrub that has health benefits and is used as a source of medicines in Asia. In this study, a full-length cDNA clone encoding ß-ring carotene hydroxylase (LcCHXB) and partial-length cDNA clones encoding phytoene synthase (LcPSY), phytoene desaturase (LcPDS), ξ-carotene desaturase (LcZDS), lycopene ß-cyclase (LcLCYB), lycopene ε-cyclase (LcLCYE), ε-ring carotene hydroxylase (LcCHXE), zeaxanthin epoxidase (LcZEP), carotenoid cleavage dioxygenase (LcCCD1), and 9-cis epoxycarotenoid dioxygenase (LcNCED) were identified in L. chinense. The transcripts were constitutively expressed at high levels in leaves, flowers and red fruits, where the carotenoids are mostly distributed. In contrast, most of the carotenoid biosynthetic genes were weakly expressed in the roots and stems, which contained only small amounts of carotenoids. The level of LcLCYE transcripts was very high in leaves and correlated with the abundance of lutein in this plant tissue. During maturation, the levels of lutein and zeaxanthin in L. chinense fruits dramatically increased, concomitant with a rise in the level of ß-cryptoxanthin. LcPSY, LcPDS, LcZDS, LcLCYB, and LcCHXE were highly expressed in red fruits, leading to their substantially higher total carotenoid content compared to that in green fruits. Total carotenoid content was high in both the leaves and red fruits of L. chinense. Our findings on the biosynthesis of carotenoids in L. chinense provide insights into the molecular mechanisms involved in carotenoid biosynthesis and may facilitate the optimization of carotenoid production in L. chinense.

Identification of phenylpropanoid biosynthetic genes and phenylpropanoid accumulation by transcriptome analysis of Lycium chinense.

BACKGROUND: Lycium chinense is well known in traditional Chinese herbal medicine for its medicinal value and composition, which have been widely studied for decades. However, further research on Lycium chinense is limited due to the lack of transcriptome and genomic information. RESULTS: The transcriptome of L. chinense was constructed by using an Illumina HiSeq 2000 sequencing platform. All 56,526 unigenes with an average length of 611 nt and an N50 equaling 848 nt were generated from 58,192,350 total raw reads after filtering and assembly. Unigenes were assembled by BLAST similarity searches and annotated with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) orthology identifiers. Using these transcriptome data, the majority of genes that are associated with phenylpropanoid biosynthesis in L. chinense were identified. In addition, phenylpropanoid biosynthesis-related gene expression and compound content in different organs were analyzed. We found that most phenylpropanoid genes were highly expressed in the red fruits, leaves, and flowers. An important phenylpropanoid, chlorogenic acid, was also found to be extremely abundant in leaves. CONCLUSIONS: Using Illumina sequencing technology, we have identified the function of novel homologous genes that regulate metabolic pathways in Lycium chinense.

Agrobacterium tumefaciens-mediated transformation of Phellodendron amurense Rupr. using mature-seed explants.

An efficient transformation protocol was developed for Agrobacterium-mediated transformation of Phellodendron amurense Rupr. for using explants from mature seeds. The binary vector pCAMBIA1303, which contained hygromycin phosphotransferase (hptII) as a selectable marker gene and ß-glucuronidase (GUS) as a reporter gene, was used for transformation studies. Different factors that affect survival of transformed buds, namely Agrobacterium infection method, bacterial strain, pre-culture duration, acetosyringone concentration, co-culture duration, and co-culture temperature were examined and optimized for transformation efficiency on the basis of GUS staining of hygromycin-resistant buds. Polymerase chain reaction (PCR), Southern blot and reverse transcription PCR confirmed the presence of the GUS gene. A transformation frequency of 13.1 % was achieved under optimized conditions for transformation (A. tumefaciens strain EHA105, 4 days co-cultivation at 4 °C, and infection of the pre-cultured mature-seed explants for 2 days). This is the first report of a successful genetic transformation protocol for P. amurense.

Case Report: Occlusion of the foramen of Monro treated with endoscopic septostomy and foraminotomy in a preterm neonate.

Background: Hydrocephalus is a brain abnormality frequently encountered in neonates. There are several known etiologies of hydrocephalus, which can be classified as either congenital or acquired. Occlusion of the foramen of Monro (FOM) is a cause of hydrocephalus and can be either congenital or secondary to various disorders. Idiopathic obstruction of the FOM presenting as prenatal ventriculomegaly is extremely rare but has been reported. Case presentation: We present the case of a preterm newborn with severe bilateral hydrocephalus due to FOM occlusion in the prenatal period. Although the neonate had normal head circumference and no clinical symptoms after birth, brain sonography revealed progressive ventriculomegaly. Further image revealed bilateral ventriculomegaly with normal-sized third and fourth ventricles. We suspected a complete obstruction of the right and a partial obstruction of the left of the FOM. The neonate underwent endoscopic septostomy and foraminotomy, resulting in improvement. Conclusion: We report a case of preterm FOM occlusion in the youngest and smallest neonate to date. Endoscopic septostomy and foraminotomy were performed in order to avoid ventriculoperitoneal shunt-related complications, highlighting the viability of endoscopic procedures which should be the primary treatment in preterm neonates with FOM occlusion.

Astragaloside IV alleviates cytarabine-induced intestinal mucositis by remodeling macrophage polarization through AKT signaling.

BACKGROUND: Intestinal mucositis (IM) is one of the common side effects of chemotherapy with Cytarabine (Ara-C) and contributes to the major dose-limiting factor of chemotherapy, while the effective drug for IM is little. Astragalus, one of the main active components extrated from the roots of Astragalus membranaceus (AS-IV), is a common Chinese herbal medicine used in gastrointestinal diseases. However, the effect and mechanism of AS-IV on IM is unclear. Accumulating evidence suggests that M1 macrophages play a pivotal role in IM progression. PURPOSE: The purpose of the study was to explore the protection of AS-IV and its potential molecular mechanism on intestinal mucositis injury induced by Ara-C. METHOD: The protective effect of AS-IV was investigated in LPS-induced macrophages and Ara-C-induced intestinal mucositis mouse model. H&E, immunofluorescence and western blotting were used to evaluate the damage in different doses of Ara-C. Silencing AKT targeted by siRNA was performed to explore the potential mechanisms regulating macrophage polarization effect of Ara-C, which was investigated by CCK-8, immunofluorescence and western blotting. Flow cytometry, immunofluorescence and Western blotting were used to detect macrophage surface marker proteins and inflammatory genes to explore the potential molecular mechanism of AS-IV regulating macrophage polarization. RESULTS: The Cytarabine intervention at dose of 100mg/kg significantly induced IM in mice, with the ileum the most obvious site of injury, accompanied by decreased intestinal barrier, intestinal macrophage polarization to M1 and inflammation response. The administration of AS-IV improved weight loss, food intake, ileal morphological damage, intestinal barrier destruction and inflammatory factor release in mice induced by Ara-c, and also suppressed macrophage polarization to M1, regulating in phenotypic changes in macrophages. In vitro, the expression of M1 macrophage surface marker protein was markedly decreased in LPS-induced macrophages after silencing AKT. Similarly, the western blotting of intestinal tissues and molecular docking indicated that the key mechanisms of AS-IV were remodel AKT signaling, and finally regulating M1 macrophages and decrease inflammation response. CONCLUSION: Our study highlights that AS-IV exerts protective effect in Ara-C-induced IM through inhibit polarization to M1 macrophages based on AKT, and AS-IV may serve as a novel AKT inhibitor to counteract the intestinal adverse effects of chemotherapeutic agents.

Ursolic acid enhances mouse liver regeneration after partial hepatectomy.

CONTEXT: Ursolic acid is a pentacyclic triterpenoid which has hepatoprotective and antihepatotoxic activities. OBJECTIVE: This study investigated whether ursolic acid is able to stimulate liver regeneration in partially hepatectomized mice. MATERIALS AND METHODS: Ursolic acid or the vehicle solution was orally administered to the experimental, sham-operated and vehicle-treated group mice for 7 days, positive control animal (mice) was treated with recombinant human hepatocyte growth factor (rhHGF), and then the 70% liver partial hepatectomy was performed. The liver mass recovery rate was estimated by measuring the ratios of mice liver weight to body weight. The liver cells undergoing DNA synthesis were identified by immunohistochemistry analysis using monoclonal anti-BrdU antibodies. The expression levels of cyclin D1, cyclin E and C/EBP proteins (C/EBPα and C/EBPß) were detected by the Western blotting technique. RESULTS: Our results showed administration of ursolic acid significantly increased the ratio of the liver to body weight and BrdU labeling index at 36 and 48 h after partial hepatectomy, and the potency of UA is similar to rhHGF treated positive control mice. In addition, ursolic acid treatment significantly increased cyclin D1, cyclin E and C/EBPß protein expression levels at 36 h after liver PHx compared with the vehicle-treated control mice. DISCUSSION AND CONCLUSION: All these results suggest that ursolic acid stimulates liver proliferation after partial hepatectomy, and this effect may be associated with the stimulation of C/EBPß expression.

Soft-tissue characteristics of operated unilateral complete cleft lip and palate patients in mixed dentition.

PURPOSE: The purpose of the study was to provide quantitative information about the facial soft-tissue characteristics of operated unilateral complete cleft lip and palate (UCCLP) children compared with healthy children during mixed dentition. METHODS: Lateral cephalometric radiographs of 48 children with UCCLP who had been operated on before the age of 2 years were analyzed and compared with those of a control group of 60 healthy children with the same age, sex, and ethnic characteristics. RESULTS: The children with operated UCCLP differed from the control group by having a more concave profile, flatter nasal tip, more retrognathic basis nasi, shorter upper lip, thicker upper and lower lip, reduced upper-lip projection, and increased lower-lip projection. CONCLUSIONS: The facial soft-tissue morphology in operated UCCLP patients differed from normal controls of the same age, sex, and ethnic group. It may be necessary for children with UCCLP operated before 2 years of age to have some preventive treatment.

Force balance reconstruction of orbicularis oris in correction of unilateral cleft lip deformity.

OBJECTIVES: Short-term outcome evaluation for the correction of unilateral cleft lip deformity with a new technique. METHODS: Forty-four patients with unilateral cleft lip deformity were included in the study and in which the orbicularis oris muscle was reconstructed to achieve the optimal force balance of reconstructed orbicularis oris. The photometric two-dimensional indexes, including the philtrum oblique angle and asymmetry ratios (lip height, lip width, vertical distance from the white roll to the vermilion bottom at the Cupid's bow point, and vertical distance from the Cupid 's bow points to facial midline), were employed to measure and evaluate the outcome. RESULTS: Several indexes showed statistically significant difference, and they included the philtrum oblique angle, asymmetry ratio of the lip height, and asymmetry ratio of the vertical distance from the white roll to the vermilion bottom at Cupid ' s bow points (P<0.05). CONCLUSIONS: The results suggested that the new muscle reconstruction technique can significantly improve the short-term outcome of the correction of unilateral cleft lip deformity.

Short-term nasal symmetry repaired by force-balanced muscular reconstruction technique.

OBJECTIVES: This study aimed to compare the postoperative outcome of the new and classical muscular reconstruction technique combined with nasal internal-fixation method for secondary deformity post unilateral cleft lip repair. A rationale is provided for the further surgical improvement of secondary deformities. METHODS: Sixty patients aged 4-18 years with secondary unilateral cleft lip-nose deformity were involved in this research. The deformities of 28 patients were repaired using the muscular force balance technique through nasal internal fixation method, and 32 were repaired using classical muscular reconstruction technique. Two-dimensional analysis was used to evaluate the nose-lip morphology of pre- and post-operative patients through standardized photographs seven days after surgery. RESULTS: Compared with preoperative nasal morphology in the muscular force balance technique group, the 7-days postoperative results of this group showed the significantly improved short-term outcomes in the correction of columellar deflection, alar rim angle, nasal shape, and the symmetry of alar base width, nostril width, nostril height, alar rim angle (P<0.05). CONCLUSIONS: The new muscular reconstruction technique with nasal internal-fixation method has a significant effect on nasal repair.

Evaluation of fistula rates in three cleft palate techniques without relaxing incisions.

The aim of the present study was to investigate the incidence of postoperative fistula formation from a hybrid cleft palate repair compared to that from two well-established techniques. We performed a modified technique, Sommerlad-Furlow (SF), which combined the repositioning of the levator veli palatini muscles as described by Sommerlad with the double opposing Z-plasty of Furlow to lengthen the soft palate. A retrospective cohort study was conducted to evaluate patients who underwent cleft palate repair utilizing SF, Sommerlad, or Furlow techniques with the incidence of palatal fistula as the target endpoint. A total of 1,164 patients were included in the present study and underwent the following techniques: 603 cases with SF, 244 cases with Furlow, and 317 cases with Sommerlad. In addition to not requiring relaxing incisions, SF advantages included a consistently lower fistula rate compared to that of the Sommerlad technique, as well as the lowest fistula rate in patients with both hard and soft palate clefts without a cleft lip (OR:2.62 95% CI: 1.35, 5.09). However, the differences among the three techniques did not reach statistical significance in terms of a bilateral or unilateral cleft lip/palate, or in patients with a soft palate only or a submucosal cleft palate(OR: 2.22,95% CI:0.77, 6.37). Based on the results of our study, the Somerlad-Furlow technique should be preferred whenever possible.

Lithium-induced overexpression of ß-catenin delays murine palatal shelf elevation by Cdc-42 mediated F-actin remodeling in mesenchymal cells.

BACKGROUND: Lithium chloride (LiCl) is widely used for the treatment of manic and other psychotic disorders, but the administration of lithium can result in several congenital defects in the fetus, including cleft palate (Meng, Wang, Torensma, Jw & Bian, 2015) (Szabo, 1970). However, the mechanism of Lithium's action as a developmental toxicant in palatogenesis is not well known. METHODS: In this study, hematoxylin-eosin and immunofluorescence staining were employed to evaluate the phenotypes and the expression of related markers in the LiCl-treated mice model. The palatal mesenchymal cells were cultured in vitro, and stimulated with LiCl or SKL2000, and co-treated with CASIN. ß-catenin protein and other cytoskeleton associated markers were evaluated by Western blotting. RESULTS: We found that Lithium disrupted palate elevation by increasing the expression of ß-catenin in C57BL/6J mice with the high incidence of cleft palate (62.5%). LiCl disturbed the F-actin responsible for cytoskeletal remodeling in mesenchymal cells, which proved to be essential in generating the elevating force during palatal elevation. Additionally, our Western blotting analysis revealed that the overexpression of ß-catenin resulted in up-regulation of Cdc42, which mediated the downstream F-actin synthesis. CONCLUSIONS: We concluded the LiCl-induced ß-catenin overexpression delayed murine palatal shelf elevation by disturbing Cdc42 mediated F-actin cytoskeleton synthesis in the palatal mesenchyme.

Vitamin B12 counteracts dexamethasone-induced proliferation and apoptosis during key periods of palatogenesis in mice.

B vitamins rescue cleft palate induced by glucocorticoids in rodents; however, the mechanism of this effect remains largely unknown. The objective of our study was to assess the effect of dexamethasone and Vitamin B12 on cell proliferation and apoptosis during palatogenesis. In our study, mesenchymal cell proliferation in mouse embryonic palates decreased when the subjects were administered dexamethasone at embryo day 13.5 (E 13.5). However, mesenchymal cell proliferation was increased after dexamethasone exposure at E 14.0 and E 14.5 in comparison with the control group. After Vitamin B12 treatment, proliferation of mesenchymal cells was restored. No apoptosis was detected until bilaterial palatal shelves adhered and formed a medial epithelium seam in the control group and Vitamin B12-treated group. However, the apoptotic cells were detected under the medial edge epithelium before the palate contacted after dexamethasone treatment. The results suggested that Vitamin B12 restored proliferation, which had been reduced by dexamethasone via a delayed cellular cycle and apoptosis. This study implies that Vitamin B12 may be used to prevent or alleviate cleft palate induced by dexamethasone during embryonic palatogenesis.

Is it possible to antagonize 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin- induced cleft palate by prenatal administration of folic acid? An experimental study.

2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) can cause a high percentage of cleft palate in fetuses when administered during organogenesis in certain strains of mice including C57BL/6J. In this study, folic acid (FA) was tested for antiteratogenic effects on TCDD-induced cleft palate in fetal mice. The pregnant C57BL/6J mice were dosed with 24 microg TCDD/kg and/or 5 mg, 10 mg, 20 mg, 40 mg FA/kg body weight on gestation day (GD) 10. The control group mice received 50 mL sesame oil/kg body weight on GD10. The mice were sacrificed on GD12.5, GD13.5, GD14.5, GD15.5, and GD16.5. The harvested embryos were examined to detect the incidence of cleft palate and the developing palatal shelves on different phases were investigated morphologically and histologically among different groups. Total frequency of clefts was 55.56% in TCDD group and 17.50% (5 mg), 42.85% (10 mg), 42.10% (20 mg), 28.26% (40 mg) in TCDD + FA groups. FA (5 mg) reduced the incidence of the cleft palate from 55.56% to 17.50% (p = 0.005). There were no significant differences between the TCDD group and 10 mg, 20 mg, 40 mg TCDD + FA groups. Based on the these results, the present study suggests that FA can reduce the incidence of 2,3,7,8-TCDD-induced cleft palate in mice.

Unconventional [2 + 3] Cyclization Involving [1,4]-Sulfonyl Transfer to Construct Polysubstituted Fluorazones as Inhibitors of Indoleamine 2,3-Dioxygenase 1.

An unconventional [2 + 3] cyclization of pyridinium ylides with 2-ylideneoxindoles has been developed for the facile construction of pharmacologically interesting polysubstituted 9H-pyrrolo[1,2-a]indol-9-ones (fluorazones). Mechanistic studies revealed that the reaction, which has a broad substrate scope, proceeds via intermolecular [1,4]-sulfonyl transfer. Moreover, biological evaluation showed that polysubstituted fluorazone 3ak potently inhibits indoleamine 2,3-dioxygenase 1, kynurenine production, and immunotolerance in tumors.