Octacalcium phosphate collagen composite for periodontal regeneration in a canine one-wall intrabony defect.

OBJECTIVE: This study aimed to evaluate the regenerative capacities of octacalcium phosphate collagen composite (OCP/Col) in one-wall intrabony defects in dogs. The background data discuss the present state of the field: No study has assessed the efficacy of OCP/Col for periodontal regeneration therapy despite the fact that OCP/Col has proved to be efficient for bone regeneration. METHODS: In six beagle dogs, the mandibular left third premolars were extracted 12 weeks before the experimental surgery. Standardized bone defects (5 mm in height and 4 mm in width) were simulated on the distal surface of the second premolars and mesially on the fourth premolars. The defect was filled with either OCP/Col (experimental group) or left empty (control group). Histological and histomorphometric characteristics were compared 8 weeks after surgery. RESULTS: No infectious or ankylotic complications were detected at any of the tested sites. The experimental group exhibited a significantly greater volume, height, and area of newly formed bone than the control group. The former also showed a greater height of the newly formed cementum than the latter, although the results were not statistically significant. The newly formed periodontal ligaments were inserted into newly formed bone and cementum in the experimental group. CONCLUSION: OCP/Col demonstrated high efficacy for bone and periodontal tissue regeneration that can be successfully applied for one-wall intrabony defects.

A presynaptic source drives differing levels of surround suppression in two mouse retinal ganglion cell types.

In early sensory systems, cell-type diversity generally increases from the periphery into the brain, resulting in a greater heterogeneity of responses to the same stimuli. Surround suppression is a canonical visual computation that begins within the retina and is found at varying levels across retinal ganglion cell types. Our results show that heterogeneity in the level of surround suppression occurs subcellularly at bipolar cell synapses. Using single-cell electrophysiology and serial block-face scanning electron microscopy, we show that two retinal ganglion cell types exhibit very different levels of surround suppression even though they receive input from the same bipolar cell types. This divergence of the bipolar cell signal occurs through synapse-specific regulation by amacrine cells at the scale of tens of microns. These findings indicate that each synapse of a single bipolar cell can carry a unique visual signal, expanding the number of possible functional channels at the earliest stages of visual processing.

Association between early-term birth and hypoglycaemia in large-for-gestational-age neonates:A retrospective cohort study.

BACKGROUND: The effect of early-term birth on the development of hypoglycaemia in large-for-gestational-age (LGA) neonates is yet to be clarified. This study aimed to clarify the association between hypoglycaemia and early-term birth in LGA neonates. METHODS: This single-centre retrospective cohort study evaluated LGA neonates born at term at Tsurugi Municipal Handa Hospital, Japan. Blood glucose levels were measured immediately and at 1, 2, and 4 hours after birth. The association between early-term birth and hypoglycaemia was evaluated using logistic regression analysis. The prevalence of severe hypoglycaemia and hypoglycaemia according to its timing of development was analysed using Fisher's exact test. RESULTS: In total, 295 neonates were included. Among them, 113 neonates (38.3%) were born at early term and 91 infants (30.8%) had hypoglycaemia. Logistic regression analysis showed a significant association between early-term birth and hypoglycaemia (adjusted odds ratio [95% confidence interval]:2.691 [1.597 to 4.535]). However, there was no significant between-group difference among those with severe hypoglycaemia. CONCLUSIONS: Among LGA neonates, early-term birth is positively associated with neonatal hypoglycaemia. This indicates that among LGA neonates, those born at early term require more careful observation for hypoglycaemia than do those born at later term. J. Med. Invest. 70 : 476-482, August, 2023.

Neonatal hyperkalemia associated with maternal ritodrine: A retrospective study.

BACKGROUND: We recently reported on a late preterm infant born at 36 weeks' gestation with serious arrhythmia due to hyperkalemia associated with long-term maternal ritodrine administration. It is unknown whether ritodrine alone increases the risk of neonatal hyperkalemia in infants born at 34-36 weeks' gestation. METHODS: This single-center, retrospective, cohort study enrolled late preterm infants (34-36 gestational weeks) born between 2004 and 2018. Cases with maternal magnesium sulfate use were not sufficient for statistical analysis and so were excluded from the study. Risk factors for the occurrence of hyperkalemia were determined based on clinical relevance and previous reports. RESULTS: In all, 212 late preterm infants with maternal ritodrine use and 400 infants without tocolysis were included in the study. Neonatal hyperkalemia occurred in 5.7% (12/212) in the ritodrine group and 1.8% (7/400) in the control group. The risk of neonatal hyperkalemia was significantly increased by maternal ritodrine administration with a crude odds ratio (OR) of 3.37 (95% confidence interval [CI]: 1.30-8.69; p < 0.01) and an adjusted OR of 3.71 (95% CI: 1.41-9.74; p < 0.01) on multivariable analysis. Long-term tocolysis (≥28 days) with ritodrine increased the risk of neonatal hyperkalemia with 9.3% (11/118) of infants developing hyperkalemia (adjusted OR 4.86; 95% CI: 1.59-14.83; p < 0.01). Neonatal hyperkalemia was not found within 2 weeks of ritodrine administration. CONCLUSION: This research suggests that late preterm infants born after long-term ritodrine administration are at risk of neonatal hyperkalemia and require special attention.

Morphological analysis of the impact of diabetes on gingival capillaries with non-invasive blood flow scope - A preliminary study.

Background/purpose: Diabetes mellitus (DM) induces microangiopathy in various tissues, leading to several complications. However, limited studies have reported the impact of diabetes on gingival capillaries. The aim of this study was to investigate the morphological evaluation and to analyze the influence of diabetes on gingival capillaries. Materials and methods: Medical interviews and periodontal examinations were performed on 29 patients with periodontitis. The subjects were divided into two groups: those with or without type 2 diabetes (DM or non-DM group). Gingival capillary density and morphology in the buccal marginal gingiva were evaluated using a capillary blood flow scope (magnification: × 560). Results: Probing pocket depth, plaque index, and gingival index were not significantly different between the DM and non-DM groups. The mean HbA1c was 7.9 ± 1.5% in the DM group (n = 14). Using an oral moisturizing gel as immersion agent, gingival capillaries can be observed under high magnification. The gingival capillary density was 10.5 ± 3.9/mm2 and 9.1 ± 2.7/mm2 in the non-DM group and DM group, respectively. There were no significant differences between the groups. Gingival capillary density was not significantly associated with probing pocket depth, plaque index, or gingival index. The proportion of capillary morphological abnormalities was significantly higher in the DM group than non-DM group. However, capillary morphological abnormalities were not significantly associated with the HbA1c. Conclusion: The present study first documented the morphological abnormalities of gingival capillaries in patients with type 2 diabetes using the capillary blood flow scope. Gingival capillary density might not be affected by diabetes.

A surge in respiratory syncytial virus infection-related hospitalizations associated with the COVID-19 pandemic: An observational study at pediatric emergency referral hospitals in Tokushima Prefecture.

The outbreak of coronavirus disease (COVID-19) resulted in implementation of social distancing and other public health measures to control the spread of infection and improve prevention, resulting in a decrease in respiratory syncytial virus (RSV) and pediatric respiratory tract infection rates. However, there was a rapid and large re-emergence of RSV infection in Japan. Notably, we were faced with a difficult situation wherein there was a shortage of hospital beds. This study aimed to examine the epidemiological patterns of RSV-related hospitalizations among children before and after the COVID-19 pandemic onset at two pediatric emergency referral hospitals covering the entire Tokushima Prefecture. Data were extracted from electronic medical records of children hospitalized with RSV infection between January 1, 2018, and December 31, 2021. All patients meeting the eligibility criteria were included in this study. The rates of study outcomes were documented annually during 2018-2021 and compared between the 2018-2020 and 2021 periods. In 2020, there was no RSV infection outbreak. Hospitalizations at the peak week in 2021 were 2.2- and 2.8-fold higher than those in 2018 and 2019, respectively. Hospitalizations in 2021 were concentrated within a short period. In addition, there was a significant increase in hospitalizations among children aged 3-5 months and those older than 24 months. The high-flow nasal cannula (HFNC) use rate nearly doubled in 2021. A new pandemic in the future may cause an outbreak of RSV infection that can result in an intensive increase in the number of hospitalizations of pediatric patients requiring respiratory support, especially in infants aged <6 months. There is an urgent need to improve the preparedness of medical systems, particularly in terms of the number of inpatient beds and the immediate availability of HFNC.

Osteoarticular infections at a pediatric emergency core hospital in Japan.

OBJECTIVES: Osteomyelitis (OM) and septic arthritis (SA) in childhood might cause complications, sequelae, or even death if diagnosis and treatment are delayed. Here, we examined the outcomes of OM/SA at a pediatric emergency core hospital in Japan. METHODS: This was a single-center, retrospective, observational cohort study at a pediatric emergency core hospital in Japan. Pediatric outpatients who underwent magnetic resonance imaging at the hospital in the period 2012?2020 were recruited. Primary outcomes were sequelae, recurrent symptoms, chronicity, and death. RESULTS: Fifteen OM/SA patients (9 OM, 4 SA, 2 OM+SA) were recruited. The identified major pathogens included methicillin-susceptible Staphylococcus aureus (40.0 %, n=6) and methicillin-resistant S. aureus (13.3 %, n=2). Mean time from onset to first hospital visit, hospitalization, and initiation of effective antibiotics was 2 days, 3.9?±?1.8 days, and 4.9±2.2 days, respectively. All OM/SA patients recovered without complications or sequelae. CONCLUSIONS: In this study, all patients with OM/SA showed a good prognosis. Despite the small sample size, this pilot study suggests that the pediatric emergency core system in Japan provides early treatment and a good prognosis for patients diagnosed with OM/SA. J. Med. Invest. 70 : 236-240, February, 2023.

A pediatric case of infliximab-resistant ulcerative colitis successfully treated using vedolizumab.

Pediatric ulcerative colitis is likely to be more severe than adult ulcerative colitis. Failure to thrive should be considered during therapy. A 10-year-old boy was diagnosed with ulcerative colitis based on his clinical presentation and colonoscopy and biopsy results. The administration of 5-aminosalicylic acid and prednisolone resulted in remission ; however, the symptoms reappeared after the discontinuation of prednisolone. Then, infliximab was administered ; however, the patient was resistant to it and appeared to be dependent on prednisolone. Vedolizumab, a monoclonal antibody against ?4?7 integrin, was administered, which resulted in rapid remission. A steady decrease in prednisolone followed, and remission was maintained even after prednisolone discontinuation. Vedolizumab may be effective in pediatric patients with moderate-to-severe refractory ulcerative colitis. Vedolizumab prevents lymphocytes from binding to MAdCAM-1, which is selectively expressed in the gastrointestinal submucosa, leading to the mitigation of the systemic side effects of immunosuppression, such as infections. In Japan, vedolizumab use is not yet approved for use in children, but its effectiveness and safety in children is expected to be investigated in the future. J. Med. Invest. 70 : 294-297, February, 2023.

The circadian clock in the piriform cortex intrinsically tunes daily changes of odor-evoked neural activity.

The daily activity in the brain is typically fine-tuned by the circadian clock in the local neurons as well as by the master circadian clock in the suprachiasmatic nucleus (SCN) of the hypothalamus. In the olfactory response, odor-evoked activity in the piriform cortex (PC) and olfactory behavior retain circadian rhythmicity in the absence of the SCN, yet how the circadian rhythm in the PC is achieved independently of the SCN remains elusive. Here, to define neurons regulating the circadian rhythm of the odor-evoked activity in the PC, we knocked out the clock gene Bmal1 in a host of specific neurons along the olfactory circuit. We discovered that Bmal1 knockout in the PC largely abolishes the circadian rhythm of the odor-evoked activity. We further showed that isolated PC exhibits sustained circadian rhythms of the clock gene Per2 expression. Quantitative PCR analysis revealed that expression patterns of multiple genes involved in neural activity and synaptic transmission exhibit circadian rhythm in the PC in a BMAL1-dependent manner. Our findings indicate that BMAL1 acts intrinsically in the PC to control the circadian rhythm of the odor-evoked activity in the PC, possibly through regulating expression patterns of multiple genes involved in neural activity and transmission.

Preclinical evaluation of the effect of periodontal regeneration by carbonate apatite in a canine one-wall intrabony defect model.

Objective: This study aimed to histologically compare periodontal regeneration of one-wall intrabony defects treated with open flap debridement, ß-tricalcium phosphate (ß-TCP), and carbonate apatite (CO3Ap) in dogs. Methods: The mandibular third premolars of four beagle dogs were extracted. Twelve weeks after the extraction, a one-wall bone defect of 4 mm × 5 mm (mesio-distal width × depth) was created on the distal side of the mandibular second premolar and mesial side of the fourth premolar. Each defect was randomly allocated to open flap debridement (control group), periodontal regeneration utilizing ß-TCP, or CO3Ap. Eight weeks after the surgery, histologic and histometric analyses were performed. Results: No ankylosis, infection, or acute inflammation was observed at any of the experimental sites. Newly formed bone and cementum were observed in all experimental groups. The mineral apposition rate of the alveolar bone crest was higher in the CO3Ap group than in the control and ß-TCP groups. The ratio of the new bone area was significantly higher in the CO3Ap group than in the control group (P < 0.05). The bone contact percentage of the residual granules was significantly higher in the CO3Ap group than in the ß-TCP group (P < 0.05). Conclusion: Although this study has limitations, the findings revealed the safety and efficacy of CO3Ap for periodontal regeneration in one-wall intrabony defects in dogs, and CO3Ap has a better ability to integrate with bone than ß-TCP.

Prognostic factors affecting periodontal regenerative therapy using recombinant human fibroblast growth factor-2: A 3-year cohort study.

Introduction: Fibroblast growth factor-2 (FGF-2) has been reported to promote periodontal tissue regeneration. However, no study has investigated the long-term prognosis of periodontal regenerative therapy using FGF-2 to date. The aim of this study was to observe the long-term outcomes as well as to investigate the factors affecting the prognosis of periodontal regenerative therapy using FGF-2. Methods: Sixty intrabony defects were prospectively investigated for three years after periodontal regenerative therapy with recombinant human FGF-2 (rhFGF-2) by evaluating probing pocket depth (PPD) and radiographic bone defect depth (RBD). The factors influencing RBD were assessed by conducting a multivariate linear regression analysis after adjusting for confounders. Results: The mean age of the participants was 62.4 ± 13.4 years, and baseline PPD and RBD were 6.1 ± 1.9 mm and 4.5 ± 1.8 mm, respectively. At six months, one year, and three years after surgery, PPD and RBD had significantly improved to 4.2 ± 1.7, 3.7 ± 1.4, 4.0 ± 1.9 mm and to 3.08 ± 2.05, 2.73 ± 1.90, 2.51 ± 2.15 mm, respectively. At the three-year examination, a significant positive association was deteced between RBD reduction and RBD at baseline, while the association was not significant between RBD reduction and the radiographic bony angle, number of bony walls of the defect, or the furcation involvement at baseline. Conclusions: rhFGF-2 was effective for alveolar bone regeneration in patients with periodontitis and maintained the improved parameters over the three-year observation period. The radiographic bone defect depth at baseline was found to be the factor affecting the periodontal regenerative therapy using rhFGF-2 in the intrabony defects. Trial registration number: UMIN000027979.

Hierarchical partner selection shapes rod-cone pathway specificity in the inner retina.

Neurons form stereotyped microcircuits that underlie specific functions. In the vertebrate retina, the primary rod and cone pathways that convey dim and bright light signals, respectively, exhibit distinct wiring patterns. Rod and cone pathways are thought to be assembled separately during development. However, using correlative fluorescence imaging and serial electron microscopy, we show here that cross-pathway interactions are involved to achieve pathway-specific connectivity within the inner retina. We found that A17 amacrine cells, a rod pathway-specific cellular component, heavily bias their synaptogenesis with rod bipolar cells (RBCs) but increase their connectivity with cone bipolar cells (CBCs) when RBCs are largely ablated. This cross-pathway synaptic plasticity occurs during synaptogenesis and is triggered even on partial loss of RBCs. Thus, A17 cells adopt a hierarchical approach in selecting postsynaptic partners from functionally distinct pathways (RBC>CBC), in which contact and/or synaptogenesis with preferred partners (RBCs) influences connectivity with less-preferred partners (CBCs).

Effect of Platelet-Rich Plasma on Autologous Chondrocyte Implantation for Chondral Defects: Results Using an In Vivo Rabbit Model.

Background: Articular cartilage repair remains challenging despite the availability of techniques, including autologous chondrocyte implantation (ACI) for repairing large cartilage defects. Platelet-rich plasma (PRP) therapy, a novel therapy focused on chondrocyte regeneration, needs to be investigated regarding its potential to improve the outcomes of ACI. Purpose: To examine the effect of PRP therapy on the outcomes of cartilage repair using the ACI procedure in a rabbit model of knee joint cartilage damage. Study Design: Controlled laboratory study. Methods: A total of 30 knees in 15 Japanese White rabbits (joint cartilage damage model) were divided into nontreatment (n = 7), PRP (n = 8), ACI (n = 7), and combined ACI and PRP (n = 8) groups. At 4 weeks and 12 weeks postoperatively, histological and visual examination of the surgical site was performed, and the regenerated cartilage and calcified bone areas were measured by imaging the specimens. Results: Pretransplantation evaluation in the cultured cartilage showed the histological properties of hyaline cartilage. At 4 weeks postoperatively, the regenerated cartilage area at the surgical site showed a larger safranin O-positive area in the ACI group (2.73 ± 4.46 mm2) than in the combined ACI and PRP group (1.71 ± 2.04 mm2). Calcified bone formation in the ACI group was relatively lower than that in the other groups. Cartilage repair failure occurred in all groups at 12 weeks postoperatively. Conclusion: The authors found no positive effects of PRP on the outcomes of ACI in a rabbit model. There was a smaller safranin O-positive region with the addition of PRP to ACI compared with ACI alone. In the subchondral bone, bone formation might have been promoted by PRP. Clinical Relevance: Administering PRP at the time of ACI may not have a positive effect and may have deleterious effects on cartilage engraftment and regeneration.

Influence of the bone graft materials used for guided bone regeneration on subsequent peri-implant inflammation: an experimental ligature-induced peri-implantitis model in Beagle dogs.

PURPOSE: We aimed to histologically evaluate the influence of bone materials used during guided bone regeneration (GBR) on subsequent peri-implantitis in an experimental ligature-induced peri-implantitis model in beagle dogs. METHODS: Bilateral mandibular premolars (PM2-4) were extracted from six beagle dogs. After 3 months, standardized bone defects (3 mm [mesio-distal width] × 2 mm [bucco-lingual width] × 3 mm [depth]) were created in the experimental group, with simultaneous dental implant placement at the center of the defects. The defects were randomly filled with either autograft (AG) or deproteinized bovine bone mineral (DBBM) and covered with a collagen membrane. In the control group, implant fixtures were placed without creating an intrabony defect. After 3 months, a healing abutment was placed. Four weeks later, a 3-0 silk thread was ligated around the implants to induce peri-implantitis. After 4 weeks, the specimens were dissected and histologically examined. RESULTS: There were no clinical findings of inflammation until silk thread ligation. Four weeks after the onset of peri-implantitis, gingival redness and swelling were seen with mild resorption of the peri-implant bone on dental radiographs. There were no significant differences between the AG, DBBM, and control groups for the following parameters: bone-to-implant contact, distance from the implant shoulder to the base of the bone defect, area of bone defect, and area of new bone. CONCLUSIONS: Within the limitations of this study, it can be concluded that peri-implant tissues after GBR using AG and DBBM underwent the same degree of bone resorption by peri-implantitis as the no defect group.

Patient attendance at a pediatric emergency referral hospital in an area with low COVID-19 incidence.

The purpose of this study was to clarify the effects of individual infection control measures and physical distancing on pediatric medical care in a local prefecture in Japan, where the incidence of coronavirus disease (COVID-19) in pediatric patients was extremely low. We extracted data from hospital records on the number of outpatients, inpatients, infectious disease consultations, and consultations for representative pediatric diseases. We compared attendance in 2017-2019, before the COVID-19 pandemic, with 2020, when COVID-19 spread to Japan. There were no COVID-19 patients in the pediatric department during the study period. The total number outpatient visits decreased by 24.4%, and the number of hospital admissions, excluding neonatal care unit admissions, decreased by approximately 35%. There was a marked reduction in the number of hospitalizations for infectious diseases such as influenza (-74.8%) and respiratory syncytial virus infection (-93.5%), and the number of hospitalizations for bronchitis/pneumonia, Kawasaki disease, and bronchial asthma decreased. In contrast, the number of clinical psychological interventions and cases reported to the child guidance center increased. In the context of pandemic infectious diseases, it is important to control the spread of problematic infectious diseases by individual infection control measures and physical distancing. However, it is necessary to maintain social life as much as possible for the mental health and physical development of children.

Escherichia coli pyomyositis in a patient with Down syndrome: A case report.

Pyomyositis is an infection of the skeletal muscle that involves intramuscular abscess formation. It is typically caused by gram-positive bacteria, especially Staphylococcus aureus. Few cases of Escherichia coli pyomyositis have been reported in immunocompromised adult patients, while none have been reported in children. We present a case of a 4-year-old boy with Down syndrome who developed Escherichia coli pyomyositis. The patient presented to our hospital with a fever and right forearm swelling. The magnetic resonance imaging findings suggested pyomyositis of the right forearm muscle and osteomyelitis of the distal radius. Both the blood and puncture fluid cultures were negative. Cefazolin and vancomycin were administered, and his blood examination results and right forearm swelling improved; however, a slight fever persisted. The multiplex polymerase chain reaction isolated the chuA gene but not the YjaA gene; thus the patient was diagnosed with pyomyositis and osteomyelitis caused by Escherichia coli group D. The cefazolin was substituted with meropenem, and the vancomycin was discontinued. Thereafter, his fever promptly improved, which indicated that the cause of persistent fever was vancomycin drug fever. The patient was discharged after receiving 3 weeks of intravenous antimicrobial therapy, and recovered fully with no long-term sequelae. To the best of our knowledge, this is the first reported case of Escherichia coli pyomyositis in a child. The findings in this case suggest that Escherichia coli should be considered when choosing initial empiric therapy for pyomyositis, especially in children with underlying conditions.

Spatial and temporal diversity of DCLK1 isoforms in developing mouse brain.

Doublecortin-like kinase 1 (DCLK1) is a Doublecortin family kinase involved in a range of brain development processes including cell migration, axon/dendrite growth, and synapse development. The Dclk1 gene potentially generates multiple splicing isoforms, but the detailed expression patterns in the brain as well as in vivo functions of each isoform are still incompletely understood. Here we assessed expression patterns of DCLK1 isoforms using multiple platforms including in silico, in situ, and in vitro datasets in the developing mouse brain, and show quantitative evidence that among the four DCLK1 isoforms, DCLK1-L and DCL are mainly expressed in the embryonic cortex whereas DCLK1-L and CPG16 become dominant compared to DCL and CARP in the postnatal cortex. We also provide compelling evidence that DCLK1 isoforms are distributed in the partially distinct brain regions in the embryonic and the postnatal stages. We further show that overexpression of DCLK1-L, but not the other isoforms, in neural progenitors causes severe migration defects in the cortex, and that the migration defects are dependent on the kinase activity of DCLK1-L. Our data thus uncover partially segregated localization of DCLK1 isoforms in the developing mouse brain and suggest different roles for distinct DCLK1 isoforms in the brain development and function.

Adeno-Associated Virus-Mediated Single-Cell Labeling of Mitral Cells in the Mouse Olfactory Bulb: Insights into the Developmental Dynamics of Dendrite Remodeling.

Neurons typically remodel axons/dendrites for functional refinement of neural circuits in the developing brain. Mitral cells in the mammalian olfactory system remodel their dendritic arbors in the perinatal development, but the underlying molecular and cellular mechanisms remain elusive in part due to a lack of convenient methods to label mitral cells with single-cell resolution. Here we report a novel method for single-cell labeling of mouse mitral cells using adeno-associated virus (AAV)-mediated gene delivery. We first demonstrated that AAV injection into the olfactory ventricle of embryonic day 14.5 (E14.5) mice preferentially labels mitral cells in the olfactory bulb (OB). Birthdate labeling indicated that AAV can transduce mitral cells independently of their birthdates. Furthermore, in combination with the Cre-mediated gene expression system, AAV injection allows visualization of mitral cells at single-cell resolution. Using this AAV-mediated single-cell labeling method, we investigated dendrite development of mitral cells and found that ~50% of mitral cells exhibited mature apical dendrites with a single thick and tufted branch before birth, suggesting that a certain population of mitral cells completes dendrite remodeling during embryonic stages. We also found an atypical subtype of mitral cells that have multiple dendritic shafts innervating the same glomeruli. Our data thus demonstrate that the AAV-mediated labeling method that we reported here provides an efficient way to visualize mitral cells with single-cell resolution and could be utilized to study dynamic aspects as well as functions of mitral cells in the olfactory circuits.

Quality Evaluation of Human Bone Marrow Mesenchymal Stem Cells for Cartilage Repair.

Quality evaluation of mesenchymal stem cells (MSCs) based on efficacy would be helpful for their clinical application. In this study, we aimed to find the factors of human bone marrow MSCs relating to cartilage repair. The expression profiles of humoral factors, messenger RNAs (mRNAs), and microRNAs (miRNAs) were analyzed in human bone marrow MSCs from five different donors. We investigated the correlations of these expression profiles with the capacity of the MSCs for proliferation, chondrogenic differentiation, and cartilage repair in vivo. The mRNA expression of MYBL1 was positively correlated with proliferation and cartilage differentiation. By contrast, the mRNA expression of RCAN2 and the protein expression of TIMP-1 and VEGF were negatively correlated with proliferation and cartilage differentiation. However, MSCs from all five donors had the capacity to promote cartilage repair in vivo regardless of their capacity for proliferation and cartilage differentiation. The mRNA expression of HLA-DRB1 was positively correlated with cartilage repair in vivo. Meanwhile, the mRNA expression of TMEM155 and expression of miR-486-3p, miR-148b, miR-93, and miR-320B were negatively correlated with cartilage repair. The expression analysis of these factors might help to predict the ability of bone marrow MSCs to promote cartilage repair.

Site-specific regulation of oral mucosa-recruiting CD8+ T cells in a mouse contact allergy model.

Contact allergy is a T cell-mediated, delayed-type hypersensitivity generated by contact exposure of an allergen to the skin and mucosal surface. The clinical manifestations of allergic responses between the skin and oral mucosa vary and the differences in immunopathology have not been clarified. We generated hapten-induced contact hypersensitivity (CH) of the buccal mucosa (BM) in parallel studies with ear skin (ES) CH, and observed several characteristic findings of BM CH. The BM challenge induced more rapid and more severe inflammation than the ES challenge, with abundant granulocyte and CD8+ T cell infiltration. However, these inflammatory responses diminished quickly. Recruiting CD8+ T cells in the BM had higher ratios of CD62L-CD44low-hi memory-type cells, and showed impaired IFN-γ, greater PD-1, and comparable Ki-67 expression, suggesting that the recruiting-proliferating CD8+ T cells were unable to differentiate into effector T cells and converted into exhausted T cells at the local site. This finding may explain the rapid recovery of the BM from severe inflammation. Preferentially greater expression of PD-1 ligand (B7-H1), was observed in the BM epithelium under the peak inflammation, and the absence of B7-H1 further accelerated CH responses, suggesting the occurrence of PD-1:B7-H1-mediated immune regulation at the local site. Our results may facilitate the understanding of the unique features of contact allergies in the oral mucosa, and guide the development of new strategies for control of contact allergy.