Green cocoon-derived sericin reduces cellular damage caused by radiation in human keratinocytes.

Radiation therapy used in the treatment of cancer causes skin damage, and no method of care has been established thus far. Recently, it has become clear that sericin derived from silkworm cocoons has moisturizing and antioxidant functions. In addition, green cocoon-derived sericin, which is rich in flavonoids, may have enhanced functions. However, whether this green cocoon-derived sericin can reduce radiotherapy-induced skin damage is unclear. In the present study, we aimed at establishing care methods to reduce skin cell damage caused by X-irradiation using green cocoon-derived sericin. We investigated its effect on human keratinocytes using lactate dehydrogenase activity to indicate damage reduction. Our results showed that green cocoon-derived sericin reduced cell damage caused by X-irradiation. However, this effect was not observed when cells were treated before X-irradiation or with a sericin derived from white cocoons. In addition, green cocoon-derived sericin decreased the levels of reactive oxygen species and lipid peroxidation. Our results suggest that green cocoon sericin mitigates the damaging effect of X-irradiation on cells, hence presenting potential usefulness in reducing skin damage from radiation therapy and opening new avenues in the care of cancer patients.

Evaluation of the correlation between the access SARS-CoV-2 IgM and IgG II antibody tests with the SARS-CoV-2 surrogate virus neutralization test.

Fully automated immunoassays for detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies that are strongly correlated with neutralization antibodies (nAbs) are clinically important because they enable the assessment of humoral immunity after infection and vaccination. Access SARS-CoV-2 immunoglobulin M (IgM) and immunoglobulin G (IgG) II antibody tests are semi-quantitative, fully automated immunoassays that detect anti-receptor-binding domain (RBD) antibodies and might reflect nAb levels in coronavirus disease 2019 (COVID-19). However, no studies have investigated the clinical utility of these tests in association with nAbs to date. To evaluate the clinical utility of Access SARS-CoV-2 IgM and IgG II antibody tests and their correlation with the SARS-CoV-2 surrogate virus neutralization test (sVNT) that measures nAbs in patients with COVID-19, we analyzed 54 convalescent serum samples from COVID-19 patients and 89 serum samples from non-COVID-19 patients. The presence of anti-RBD antibodies was detected using Access SARS-CoV-2 IgM and IgG II antibody tests, while nAbs were measured by sVNT. The sensitivity and specificity of sVNT were 94.4% and 98.9%, respectively. There were strong positive correlations between the inhibition values of sVNT and the results of the Access SARS-CoV-2 IgM (R = 0.95, R2 = 0.90, p < 0.001) and IgG II antibody tests (R = 0.96, R2 = 0.92, p < 0.001). In terms of the presence of nAbs, the sensitivity and specificity were 98.1% and 98.9% in the IgM assay and 100.0% and 100.0% in the IgG II assay, respectively. The Access SARS-CoV-2 IgM and IgG II antibody tests showed high sensitivity and specificity for the detection of nAbs in COVID-19 patients and might be alternatives for measuring nAbs.

Cross-reactive humoral immune responses against seasonal human coronaviruses in COVID-19 patients with different disease severities.

BACKGROUND: The cross-reactive antibody response against seasonal human coronaviruses (HCoVs) was evaluated according to disease severity in patients with COVID-19 in Japan. METHODS: In total, 194 paired serum samples collected from 97 patients with COVID-19 (mild, 35; severe, 62) were analyzed on admission and during convalescence. IgG antibodies against the nucleocapsid (N) and spike (S) proteins of SARS-CoV-2 and four seasonal HCoVs (HCoV-NL63, -229E, -OC43, and -HKU1) were detected by enzyme-linked immunosorbent assays. RESULTS: There was no difference in optical density (OD) values for seasonal HCoVs on admission between the severe and mild cases. In addition, a specific pattern of disease severity-associated OD values for HCoVs was not identified. Significant increases in OD values from admission to convalescence for HCoV-HKU1and -OC43 IgG-S, and for HCoV-NL63 and -229E IgG-N were observed in the severe cases. Significant differences were observed between the mild and severe cases for HCoV-HKU1 and -OC43 IgG-S OD values during convalescence. Correlations were found between the fold changes for HCoV-OC43 IgG-S OD values, and for SARS-CoV-2 IgG-S OD values, and C-reactive protein, lactate dehydrogenase, and lymphocyte levels. CONCLUSION: There was no association between the antibody titer for seasonal HCoVs in the early phase of COVID-19 and disease severity.

[From the Standpoint of a Core Center Hospital for Cancer Genome Medicine-Establishment of a Provision System for Wide-Area Precision Oncology].

In Japan, 2 comprehensive genome profiling(CGP)tests for cancer was covered by national health insurance in June 2019, and cancer genome medicine was introduced at a total of 225 hospitals designated by the Ministry of Health, Labor and Welfare as"core center hospitals for cancer genome medicine(12 hospitals)"," core hospitals for cancer genome medicine (33 hospitals)", and"collaborative hospitals for cancer genome medicine(180 hospitals)". On the other hand, the interpretation of the results of the cancer CGP test must be discussed by an expert panel conducted at the core center hospitals for cancer genome medicine or the core hospitals for cancer genome medicine, and the results must be explained to patients in order to be covered by insurance. In other words, these hospitals are required to review not only their own cases but also those of collaborating hospitals. In addition, core center hospitals for cancer genome medicine are required to share information and develop human resources with core hospitals and collaborative hospitals for cancer genome medicine. We herein describes the system for providing cancer genome medicine in our hospital as a core center hospital for cancer genome medicine.

Computed tomography assessment of mandibular morphologic changes and the inferior mandibular border defect after sagittal split ramus osteotomy.

OBJECTIVE: This study aimed to assess mandibular morphologic changes to the condyle, ramus, mandibular body, and inferior mandibular border defect after sagittal split ramus osteotomy in class II and III patients. STUDY DESIGN: The relationships among the condyle, ramus, and mandibular body measured by computed tomography preoperatively and postoperatively were assessed and factors related to the reduction of the condylar square and mandibular inferior border defect were examined. RESULTS: Patients included 72 female patients with jaw deformity (36 skeletal class II cases, 36 skeletal class III cases). Postoperative reduction of the condylar square was significantly correlated with preoperative condylar height in patients with class II (P = .0297) vs preoperative condylar height and preoperative mandibular height in patients with class III (P < .0001). A mandibular inferior border defect was found in 18 of 72 class II sides (25.0%) and was significantly related to the position of the osteotomy line and attachment side of the inferior border cortex (P < .0001). CONCLUSIONS: This study's findings suggest that the postoperative reduction of the condyle could be associated with preoperative condylar height. However, the mandibular inferior border defect in class II advancement surgery could be independently associated with technical factors in sagittal split ramus osteotomy.

Evaluation of condylar surface CT values related to condylar height reduction after orthognathic surgery.

This study was performed to evaluate the relationship between condylar height reduction and changes in condylar surface computed tomography (CT) values in jaw deformity patients following orthognathic surgery. Mandibular advancement by sagittal split ramus osteotomy (SSRO) with Le Fort I osteotomy was performed in class II patients, and mandibular setback by SSRO with Le Fort I osteotomy was performed in class III patients. The maximum CT values (pixel values) at five points on the condylar surface and the condylar height, ramus height, condylar square, ramus angle, and gonial angle in the sagittal plane were measured preoperatively and 1 year postoperatively. Disc position was classified as anterior disc displacement (ADD) or other types by using magnetic resonance imaging (MRI). Ninety-two condyles of 46 female patients were prepared for this study. Their temporomandibular joints (TMJs) were divided into two groups based on class (46 joints in class II and 46 joints in class III) and two groups based on the findings (25 joints with ADD and 67 joints with other findings). ADD with and without reduction was observed in two joints in the class III group and in 23 joints in the class II group. The distribution of ADD incidence had not changed 1 year after surgery. Condylar height decreased 1 year after surgery in both class II patients (mandibular advancement) (p < 0.0001) and class III patients (mandibular setback) (p = 0.0306). Similarly, condylar height decreased 1 year after surgery both in patients who showed ADD (p = 0.0087) and those with other types (p = 0.0023). Significant postoperative increases at all angle sites on the condylar surface were found in the class II (p < 0.05) and ADD (p < 0.05) groups. This study showed that an enhanced condylar surface CT value might be one sign of condylar height reduction related to sequential condylar resorption, in combination with ADD.

Rejection Sensitivity and Borderline Personality Disorder Features: The Mediating Roles of Attachment Anxiety, Need to Belong, and Self-Criticism.

Rejection hypersensitivity has been considered the core feature of patients with borderline personality disorder (BPD). However, little is known about the possible developmental mechanisms that might explain the association between rejection sensitivity and BPD features. The current study investigated the mediating roles of adult attachment, need to belong, and self-criticism in the association between rejection sensitivity and BPD features in 256 healthy adults. Results indicated that attachment anxiety, need to belong, and self-criticism mediated the association between rejection sensitivity and BPD features. However, attachment anxiety and self-criticism did not moderate the mediated association between rejection sensitivity and BPD features. The findings suggest that individuals with high rejection sensitivity are more likely to be anxiously attached to significant others, which might increase the desire to be accepted by others. To satisfy this elevated need to affiliate with others, these individuals might become more self-critical, which may contribute to high BPD features.

Changes in cross-sectional measurements of masseter, medial pterygoid muscles, ramus, condyle and occlusal force after bi-maxillary surgery.

PURPOSE: The purpose of this study was to examine changes in masseter and medial pterygoid muscles, ramus, condyle and occlusal force after bi-maxillary surgery in class II and III patients. SUBJECTS AND METHODS: The subjects were 42 patients (84 sides) who underwent sagittal split ramus osteotomy with Le Fort I osteotomy (21 class II cases: mandibular advancement and 21 class III cases: mandibular setback). The cross-sectional measurements of the masseter and medial pterygoid muscles, ramus and condyle were measured in horizontal plane images by computed tomography (CT), before and 1 year after the operation. Occlusal force and contact area were also recorded before and 1 year after the operation. RESULTS: Preoperatively, class II was significantly larger than class III in masseter width (P = 0.0068), masseter area (P < 0.0001) and medial pterygoid length (P < 0.0001). However, class II was significantly smaller than class III in medial pterygoid width (P < 0.0001). After 1 year, class II was significantly smaller than class III in masseter length (P = 0.0017). Class II was still larger than class III in medial pterygoid area after 1 year (P = 0.0343). Class II was significantly larger than class III in condylar angle pre-operatively (P < 0.0001) and after 1 year (P = 0.0006). After 1 year, class II decreased significantly more than class III in condylar thickness (P = 0.0020), condylar width (P < 0.0001) and condylar area (P < 0.0001). CONCLUSION: This study suggested that changes in the cross-sectional measurements of masseter and medial pterygoid muscles and the condyle differed between class II and class III patients, although occlusal force did not significantly change 1 year after surgery in both groups.

Adaptive change in temporomandibular joint tissue and mandibular morphology following surgically induced anterior disc displacement by bFGF injection in a rabbit model.

PURPOSE: The purpose of this study was to examine the effect of injecting basic fibroblast growth factor following surgical induced anterior disc displacement in temporomandibular joints (TMJ). MATERIALS AND METHODS: Adult male Japanese white rabbits (n = 16; 2.0-2.5 kg; 10 weeks old) were assigned to experimental and control groups. In the experimental group, anterior disc displacement was induced in the bilateral TMJ. Recombinant human basic fibroblast growth factor (rh bFGF) 0.1 µg/1 µL aqueous solution was injected into the left retro-discal connective tissue close to the disc (ADL group), and saline alone was injected into the same site on the right (ADR group). In the control group, a sham operation without disc position change was performed in the bilateral TMJ (CR group and CL group). Four animals from the experimental (ADR and ADL) and control (CR and CL) groups were sacrificed at 1 and 12 weeks postoperatively to evaluate the mandibular morphology and computed tomographic (CT) value of the condylar head, using 3 dimensional computed tomography. Furthermore, cartilage layers and disc tissue were examined histologically. RESULTS: Regarding CT value at the 0° site of the condylar surface, ADR showed the lowest value after 1 week (P = 0.0325). However, there were no significant differences among the 4 groups regarding CT values at the other degree sites after 1 and 12 weeks. Regarding mandibular length, ADR showed the lowest value after 12 weeks (P = 0.0079). In condylar width, ADR showed the lowest value after 1 week (P = 0.0097). CONCLUSION: This study suggested that surgically induced anterior disc displacement could affect condylar morphology in the early stage, and could decrease mandibular length in the late stage. However, bFGF injection into the TMJ might prevent the degenerative change derived from anterior disc displacement and inhibition of sequential mandibular growth.

Relationship between occlusal force and condylar morphology in class II and III after bi-maxillary osteotomy.

PURPOSE: The purpose of this study was to examine the relationship between occlusal force and condylar morphology in class II and III after sagittal split ramus osteotomy (SSRO) with Le Fort I osteotomy. MATERIALS AND METHODS: The subjects were 42 female patients who underwent bi-maxillary surgery, and were divided into 2 groups (21 class II and 21 class III cases). They were selected randomly from among patients that underwent surgery from 2012 to 2017. Condylar height, ramus height, ramus inclination and condylar square were assessed by computed tomography (CT), preoperatively and 1 year postoperatively. Occlusal contact area and occlusal force were measured pre- and 1, 3, 6 and 12 months post-operative. RESULTS: Condylar height and ramus height of the class II advancement cases decrease more significantly than those of class III. There were no significant differences in time-course changes of occlusal force and area between the class II and III. In the class II cases, occlusal force at 1 and 3 months was significantly lower than the preoperative value (P = 0.0009, P = 0.0002). On the other hand, in class III, occlusal force at 1, 3 and 6 months (P = 0.0038, P = 0.0031, P = 0.0283) was significantly lower than the preoperative value. CONCLUSION: This study suggested that occlusal force of the class II advancement cases reached the pre-operative level earlier than that of the class III setback cases, even though condylar height decreased after surgery in the class II cases. However, a correlation between occlusal force change and condylar height reduction after surgery could not be found.

Effects of Social Exclusion on Effortful Control and Mentalizing in relation to Borderline Personality Features.

The current study investigated the effects of social interactions on effortful control (EC) and mentalizing in individuals with borderline personality disorder (BPD) features. 123 nonclinical participants completed the emotional Stroop task to assess EC and the modified Reading the Mind in the Eyes Test (RMET) to assess mentalizing capacities before and after having social interactions. The Cyberball paradigm was used to generate socially inclusive and exclusive interactions. Results indicated the high BPD group made more errors on the Stroop task following exclusive social interactions than the low BPD group. The high BPD group, compared to the low BPD group, associated fewer emotional words with facial cues following inclusive social interactions but overanalysed facial cues (hypermentalizing) following the exclusive social interaction. Exclusive social interactions hindered the inhibitory capacities in individuals with high BPD features, but inclusive social interactions facilitated. Individuals with high BPD features responded to exclusive social interactions by hypermentalizing. Thus, it was found social rejection could activate cognitive-affective processes which led to hypermentalizing and impairments in EC which in combination could explain the disruptive effects on social interactions in people with BPD features.

Rejection sensitivity and borderline personality disorder features: A mediation model of effortful control and intolerance of ambiguity.

Although past research suggests that borderline personality disorder (BPD) patients' rejection hypersensitivity may be an important factor underlying these patients' interpersonal problems, the role of cognitive factors in this association is still not well understood. The present study examined whether cognitive factors such as effortful control and intolerance of ambiguity mediated the association between rejection sensitivity and BPD features. A sample of 256 young adults completed self-report questionnaires assessing rejection sensitivity, effortful control, intolerance of ambiguity, and BPD features. Results showed that effortful control and intolerance of ambiguity mediated the association between rejection sensitivity and BPD features. The present study showed the role of cognitive aspects including both effortful control and intolerance of ambiguity in the relationship between rejection sensitivity and BPD features. However, there is a need for further research to experimentally investigate how rejection sensitivity may impact cognitive capacities in interpersonal contexts among individuals with BPD features.

Mandibular bone healing after advancement or setback surgery using sagittal split ramus osteotomy.

PURPOSE: The purpose of this study was to compare mandibular bone healing after advancement or setback surgery using sagittal split ramus osteotomy (SSRO). SUBJECTS: and Methods. The subjects were 50 patients (100 sides) who underwent bi-maxillary surgery, and were divided into 2 groups (25 class II advancement cases and 25 class III setback cases). They were selected randomly from the patients who underwent surgery between 2012 and 2017. Ramus square, ramus length and ramus width were measured in the horizontal plane image of computed tomography (CT), before and immediately after the operation, and at 1 year after the operation. RESULTS: Ramus square in the class III cases significantly increased in 1 year after the operation (P < 0.0001), meanwhile there was no change after 1 year in the class II cases. Before the operation, there were no significant differences in the all measurements between classes II and III. However, for ramus width, class III was significantly larger than class II immediately after (P = 0.0014) and at 1 year after the operation (P = 0.0003). CONCLUSION: This study suggested that post-operative change in ramus morphology was different between class II advancement surgery and class III setback surgery.

Time-course change in temporomandibular joint space after advancement and setback mandibular osteotomy with Le Fort I osteotomy.

PURPOSE: The purpose of this study was to compare time-course changes in temporomandibular joint (TMJ) space between mandibular advancement surgery and setback surgery after sagittal split ramus osteotomy (SSRO) and Le Fort I osteotomy. SUBJECTS AND METHODS: The subjects were 46 patients (92 joints) who underwent bi-maxillary surgery. The TMJ disc position was assessed by magnetic resonance imaging (MRI) and the anterior, superior, posterior, medial and lateral joint spaces were assessed by computed tomography (CT), preoperatively and at 1 week and 1 year postoperative. The 92 joints were divided into 2 groups, namely class II (n = 46 joints), and class III (n = 46 joints) (an advanced group vs a setback group). Next, the 92 joints were divided into 2 groups comprising 36 joints with anterior disc displacement joint (ADD group) and 56 joints without (non-ADD group). Time-course changes in the measurements were compared statistically between the advanced and setback groups, and between the ADD and non-ADD groups. RESULTS: There were no significant differences between the advance group and setback group regarding time-course change in all the joint spaces. However, there were significant differences between the ADD group and non-ADD group regarding time-course change in the medial, anterior, superior and posterior joint spaces (P < 0.05). CONCLUSION: This study suggested that ADD could affect the time-course change in TMJ space and condylar position after bi-maxillary osteotomy.

Comparison of temporomandibular joint and ramus morphology between class II and class III cases before and after bi-maxillary osteotomy.

PURPOSE: The purpose of this study was to compare changes in temporomandibular joint (TMJ) and ramus morphology between class II and III cases before and after sagittal split ramus osteotomy (SSRO) and Le Fort I osteotomy. MATERIALS AND METHODS: The subjects were 39 patients (78 sides) who underwent bi-maxillary surgery. They consisted of 2 groups (18 class II cases and 21 class III cases), and were selected randomly from among patients who underwent surgery between 2012 and 2016. The TMJ disc tissue and joint effusion were assessed by magnetic resonance imaging (MRI) and the TMJ space, condylar height, ramus height, ramus inclination and condylar square were assessed by computed tomography (CT), pre- and post-operatively. RESULTS: The number of joints with anterior disc displacement in class II was significantly higher than that in class III (p < 0.0001). However, there were no significant differences between the two classes regarding ratio of joint symptoms and ratio of joint effusion pre- and post-operatively. Class II was significantly better than class III regarding reduction ratio of condylar height (p < 0.0001) and square (p = 0.0005). CONCLUSION: The study findings suggest that condylar morphology could change in both class II and III after bi-maxillary surgery. The findings of the numerical analysis also demonstrated that reduction of condylar volume occurred frequently in class II, although TMJ disc position classification did not change significantly, as previously reported.

Modified hybrid fixation using absorbable plate and screw for mandibular advancement surgery.

PURPOSE: The purpose of this study was to examine the skeletal stability of mandibular advancement after sagittal split ramus osteotomy (SSRO) with modified hybrid fixation using absorbable plates and screws. MATERIALS AND METHODS: A total of 54 Japanese patients were enrolled in this study. Of them, 23 who were diagnosed with mandibular prognathism underwent setback surgery with bi-cortical plate fixation using absorbable plates and screws (setback group). Another 23 who were diagnosed with mandibular retrognathism underwent advancement surgery with modified hybrid fixation using absorbable plates (advance group), and 8 who were diagnosed with mandibular retrognathism underwent advancement surgery with titanium plates (titanium group). Skeletal stability and horizontal condylar angle were analyzed by axial, frontal, and lateral cephalograms preoperatively and at 1 month, 3 months and 1 year post-operatively. The findings were compared statistically. RESULTS: The advance group showed no significant difference compared with the titanium group. There were significant differences between the setback and advance groups regarding SNB, ANB, gonial angle, ramus inclination, occlusal plane, convexity and Me-Ag right in T1 naturally (P < 0.05). However, in T2, there were no significant differences between the groups for the other measurements, although there were significant differences in ANB, interincisal angle, occlusal plane and Me-Ag right (P < 0.05). In T3, a significant difference was seen only in Me-Ag right (P = 0.0145). CONCLUSION: This study suggested that the use of an absorbable plate and screw was useful and reliable for mandibular advancement surgery as well as mandibular setback surgery, when the fixation method was devised successfully.

Characterization of Coronal Pulp Cells and Radicular Pulp Cells in Human Teeth.

Dental pulp has garnered much attention as an easily accessible postnatal tissue source of high-quality mesenchymal stem cells (MSCs). Since the discovery of dental pulp stem cells (DPSCs) in permanent third molars, stem cells from human exfoliated deciduous teeth and from supernumerary teeth (mesiodentes) have been identified as a population distinct from DPSCs. Dental pulp is divided into 2 parts based on the developing stage: the coronal pulp and the radicular pulp. Root formation begins after the crown part is completed. We performed a sequential study to examine the differences between the characteristics of coronal pulp cells (CPCs) and radicular pulp cells (RPCs) from permanent teeth, mesiodentes, and deciduous teeth. Interestingly, although we have not obtained any data on the difference between CPCs and RPCs in permanent teeth, there are some differences between the characteristics of CPCs and RPCs from mesiodentes and deciduous teeth. The MSC characteristics differed between the RPCs and CPCs, and the reprogramming efficiency for the generation of induced pluripotent stem cells was greater in RPCs than in CPCs from deciduous teeth. The proportion of CD105+ cells in CPCs versus that in RPCs varied in mesiodentes but not in permanent teeth. The results indicate that the proportion of CD105+ cells is an effective means of characterizing dental pulp cells in mesiodentes. Taken together, the stem cells in deciduous and supernumerary teeth share many characteristics, such as a high proliferation rate and an immunophenotype similar to that of DPSCs. Thus, mesiodentes accidentally encountered on radiographs by the general dental practitioner might be useful for stem cell therapy.

Characterization of mesenchymal progenitor cells in the crown and root pulp of primary teeth.

The existence of progenitor/mesenchymal stem cells (MSCs) was demonstrated previously in human primary/deciduous teeth. In this study, we examined dental pulp cells from root portion (root cells) of primary teeth without discernible root resorption and compared them with pulp cells from the crown portion (crown cells). Root cells and crown cells were characterized and compared to each other based on progenitor/MSC characteristics and on their generation efficiency of induced pluripotent stem (iPS) cells. Root cells and crown cells included cells manifesting typical progenitor/MSC properties such as osteogenic and adipogenic differentiation potential and clonogenicity. Interestingly, root cells showed a higher expression level of embryonic stem cell marker, KLF4, than crown cells. Moreover, the number of colony-forming unit-fibroblast and cell proliferation rate were higher for root cells than crown cells, and the efficiency of generating iPS cells from root cells was approximately four times higher than that from crown cells. Taken together, these results suggest that root cells from primary teeth show the MSC-like properties and thus could be a potent alternative source for iPS cell generation and the subsequent transplantation therapy.

Periodontal tissue regeneration by transplantation of rat adipose-derived stromal cells in combination with PLGA-based solid scaffolds.

Regeneration of damaged periodontium is challenging due to its multi-tissue composition. Mesenchymalstem cell-based approaches using adipose-derived stromal cells (ASCs) may contribute to periodontal reconstruction, particularly when combined with the use of scaffolds to maintain a space for new tissue growth. The aim of this study was to assess the regenerative potential of ASCs derived from inbred or outbred rats in combination with novel solid scaffolds composed of PLGA (Poly D,L-lactic-co-glycolic acid) (PLGA-scaffolds). Cultured ASCs seeded onto PLGA scaffolds (ASCs/PLGA) or PLGA-scaffolds (PLGA) alone were transplanted into periodontal fenestration defects created in F344 or Sprague Dawley (SD) rats. Micro-CT analysis showed a significantly higher percentage of bone growth in the ASCs/PLGA groups compared with the PLGA-alone groups at five weeks after surgery. Similarly, histomorphometric analysis demonstrated thicker growth of periodontal ligament and cementum layers in the ASCs/PLGA-groups compared with the PLGA-alone groups. In addition, transplanted DiI-labeled ASCs were observed in the periodontal regenerative sites. The present investigation demonstrated the marked ability of ASCs in combination with PLGA scaffolds to repair periodontal defects.

High antitumor activity of pladienolide B and its derivative in gastric cancer.

The antitumor activity of pladienolide B, a novel splicing inhibitor, against gastric cancer is totally unknown and no predictive biomarker of pladienolide B efficacy has been reported. We investigated the antitumor activity of pladienolide B and its derivative on gastric cancer cell lines and primary cultured cancer cells from carcinomatous ascites of gastric cancer patients. The effect of pladienolide B and its derivative on six gastric cancer cell lines was investigated using a MTT assay and the mean IC50 values determined to be 1.6 ± 1.2 (range, 0.6-4.0) and 1.2 ± 1.1 (range, 0.4-3.4) nM, respectively, suggesting strong antitumor activity against gastric cancer. The mean IC50 value of pladienolide B derivative against primary cultured cells from 12 gastric cancer patients was 4.9 ± 4.7 nM, indicative of high antitumor activity. When 18 SCID mice xenografted with primary cultured cells from three patients were administered the pladienolide B derivative intraperitoneally, all tumors completely disappeared within 2 weeks after treatment. Histological examination revealed a pathological complete response for all tumors. In the xenograft tumors after treatment with pladienolide B derivative, immature mRNA were detected and apoptotic cells were observed. When the expressions of cell-cycle proteins p16 and cyclin E in biopsied gastric cancer specimens were examined using immunohisctochemistry, positivities for p16 and cyclin E were significantly and marginally higher, respectively, in the low-IC50 group compared with the high-IC50 group, suggesting the possibility that they might be useful as predictive biomarkers for pladienolide B. In conclusion, pladienolide B was very active against gastric cancer via a mechanism involving splicing impairment and apoptosis induction.