Effect of SHED-CM on DPN

Aims/Introduction: Transplantation of stem cells promotes axonal regeneration and angiogenesis in a paracrine manner. In the present study, we examined whether the secreted factors in conditioned medium of stem cells from human exfoliated deciduous teeth (SHED‐CM) had beneficial effects on diabetic polyneuropathy in mice. Materials and Methods: Conditioned medium of stem cells from human exfoliated deciduous teeth was collected 48 h after culturing in serum‐free Dulbecco's modified Eagle's medium (DMEM), and separated into four fractions according to molecular weight. Dorsal root ganglion neurons from C57BL/6J mice were cultured with SHED‐CM or DMEM to evaluate the effect on neurite outgrowth. Streptozotocin‐induced diabetic mice were injected with 100 μL of SHED‐CM or DMEM into the unilateral hindlimb muscles twice a week over a period of 4 weeks. Peripheral nerve functions were evaluated by the plantar test, and motor and sensory nerve conduction velocities. Intraepidermal nerve fiber densities, capillary number‐to‐muscle fiber ratio, capillary blood flow and morphometry of sural nerves were also evaluated. Results: Conditioned medium of stem cells from human exfoliated deciduous teeth significantly promoted neurite outgrowth of dorsal root ganglion neurons compared with DMEM. Among four fractions of SHED‐CM, the only fraction of <6 kDa promoted the neurite outgrowth of dorsal root ganglion neurons. In addition, SHED‐CM significantly prevented decline in sensory nerve conduction velocities compared with DMEM in diabetic mice. Although SHED‐CM did not improve intraepidermal nerve fiber densities or morphometry of sural nerves, SHED‐CM ameliorated the capillary number‐to‐muscle fiber ratio and capillary blood flow. Conclusions: These results suggested that SHED‐CM might have a therapeutic effect on diabetic polyneuropathy through promoting neurite outgrowth, and the increase in capillaries might contribute to the improvement of neural function

Evaluation of Surgical Stress Associated with Video-assisted Thoracic Surgery for Esophageal Cancer According to Interleukin-6 Variation in Pleural Cavity Lavage Fluid

Esophagectomy for esophageal cancer is one of the most invasive gastrointestinal surgeries. In 1996, we introduced video-assisted thoracic surgery for esophageal cancer (VATS-E) to reduce surgical stress. In 2010, we started employing artificial pneumothorax (AP) using carbon dioxide gas in VATS-E to further reduce surgical stress. In this study, we evaluated interleukin-6 (IL-6) levels in pleural cavity lavage fluid (PLF) of patients undergoing VATS-E with or without AP, and examined the effect of AP on VATS-E-induced stress. This non-randomized study included patients who underwent VATS-E with or without AP at Showa University Hospital between 2009 and 2013 and from whom PLF could be collected. IL-6 concentrations in PLF were examined before and after the thoracic part of the operation. We compared IL-6 variation, defined as the difference between IL-6 concentrations in PLF before and after the thoracic part of the operation, between patients for whom AP was used and those for whom it was not used. A total of 52 patients were included in the study; 26 underwent VATS-E with AP (group AP), and 26 underwent VATS-E without AP (group NP). IL-6 concentrations in PLF were significantly elevated immediately after the thoracic part of the operation in both groups. IL-6 variation in PLF correlated with both thoracic operative time and blood loss, which were considered practical parameters of surgical stress, and was significantly lower in group AP than in group NP. In conclusion, IL-6 variation in PLF is a useful and sensitive maker of surgical stress during VATS-E. VATS-E with AP is less invasive than VATS-E without AP because AP lowers the perioperative systemic inflammatory response to thoracic surgery

SDOP-DB: a comparative standardized-protocol database for mouse phenotypic analyses

Summary: This article reports the development of SDOP-DB, which can provide definite, detailed and easy comparison of experimental protocols used in mouse phenotypic analyses among institutes or laboratories. Because SDOP-DB is fully compliant with international standards, it can act as a practical foundation for international sharing and integration of mouse phenotypic information

Id4, a New Candidate Gene for Senile Osteoporosis, Acts as a Molecular Switch Promoting Osteoblast Differentiation

Excessive accumulation of bone marrow adipocytes observed in senile osteoporosis or age-related osteopenia is caused by the unbalanced differentiation of MSCs into bone marrow adipocytes or osteoblasts. Several transcription factors are known to regulate the balance between adipocyte and osteoblast differentiation. However, the molecular mechanisms that regulate the balance between adipocyte and osteoblast differentiation in the bone marrow have yet to be elucidated. To identify candidate genes associated with senile osteoporosis, we performed genome-wide expression analyses of differentiating osteoblasts and adipocytes. Among transcription factors that were enriched in the early phase of differentiation, Id4 was identified as a key molecule affecting the differentiation of both cell types. Experiments using bone marrow-derived stromal cell line ST2 and Id4-deficient mice showed that lack of Id4 drastically reduces osteoblast differentiation and drives differentiation toward adipocytes. On the other hand knockdown of Id4 in adipogenic-induced ST2 cells increased the expression of Pparγ2, a master regulator of adipocyte differentiation. Similar results were observed in bone marrow cells of femur and tibia of Id4-deficient mice. However the effect of Id4 on Pparγ2 and adipocyte differentiation is unlikely to be of direct nature. The mechanism of Id4 promoting osteoblast differentiation is associated with the Id4-mediated release of Hes1 from Hes1-Hey2 complexes. Hes1 increases the stability and transcriptional activity of Runx2, a key molecule of osteoblast differentiation, which results in an enhanced osteoblast-specific gene expression. The new role of Id4 in promoting osteoblast differentiation renders it a target for preventing the onset of senile osteoporosis

Distinct TERT promoter C228T and C250T mutations in a patient with an oligodendroglioma : A case report

The majority of oligodendroglial tumors harbor mutations in the telomerase reverse transcriptase (TERT) gene (TERT) promoter and the isocitrate dehydrogenase 1/2 (IDH1/2) gene (IDH1/2), as well as 1p/19q codeletion. Generally, TERT promoter mutations, C250T and C228T, are mutually exclusive. We present a case of oligodendroglioma harboring both C250T and C228T mutations in TERT promoter. A 38-year-old man presented with grand mal seizures and underwent a resection surgery for a left frontal lobe tumor. He was pathologically diagnosed as having oligodendroglioma and was carefully observed. At 48 years of age, he underwent another resection surgery due to tumor regrowth, with the pathological diagnosis of anaplastic oligodendroglioma. Genetic analysis of the initial tumor specimen revealed IDH1 R132H mutation and both C250T and C228T mutations in TERT promoter. Using mutation-specific primers, two mutations were considered to be distributed in different alleles. In the tumor specimen obtained during the second surgery, IDH1 R132H mutation was detected to be similar to that of the initial specimen; however, only C228T mutation was detected in TERT promoter. The 1p/19q codeletion was detected in both the initial and recurrent tumor specimens. According to the sequencing data from the two tumor specimens, although TERT promoter mutation has been considered to be an early genetic event in the tumorigenesis of oligodendroglial tumors, it is likely that the C250T and C228T mutations in TERT promoter are subclonally distributed in the same tumor specimen of the present case

Endoscopic tympanoplasty type I using interlay technique

Abstract Background Tympanoplasty using the interlay technique has rarely been reported in transcanal endoscopic ear surgery, unlike the underlay technique. This is because many surgeons find it challenging to detach the epithelial layer of the tympanic membrane using only one hand. However, the epithelial layer can be easily detached from the inferior part of the tympanic membrane. Another key point is to actively improve anteroinferior visibility even if the overhang is slight because most perforations and postoperative reperforations are found in the anteroinferior quadrant of the tympanic membrane. We report the application of the interlay technique in endoscopic tympanoplasty type I for tympanic perforations. Methods We retrospectively reviewed the medical records of 51 patients who had undergone tympanoplasty using the interlay technique without ossiculoplasty between 2017 and 2020. We then compared the data with those of patients who underwent microscopic surgery (MS) using the underlay technique between 1998 and 2009 (n = 104). No other technique was used in each group during this period. Repair of tympanic membrane perforation and hearing outcomes were assessed for > 1 year postoperatively. Results The perforation sites were limited to the anterior, posterior, and anterior–posterior quadrants in 23, 1, and 27 ears, respectively. Perforations were closed in 50 of the 51 ears (98.0%), and the postoperative hearing was good (average air-bone [A-B] gap was 6.8 ± 5.8 dB). The surgical success rate for the repair of tympanic membrane perforation was not significantly different from the MS group (93.3%, P = 0.15). The average postoperative average A-B gap in the group that underwent the interlay technique was significantly different from that in the MS group (10.1 ± 6.6 dB, P < 0.01). Conclusion The interlay technique should be considered as one of the treatment methods in endoscopic surgery for tympanic perforations. Further study of the postoperative outcomes of this procedure should be conducted to establish the optimal surgical procedure for tympanic perforations. Trial registration: This study was retrospectively approved by the Institutional Review Board of the Jikei University, Tokyo, Japan (approval number: 32-205 10286). Video abstract Video abstrac

Diencephalic pediatric low-grade glioma harboring the BRAF V600E mutation presenting with various morphologies in sequential biopsy specimens

A 5-year-old boy underwent biopsy of an intra-axial calcified tumor in the hypothalamus, which was incidentally found. Based on the presence of ganglion-like cells combined with glial cell element, the pathological diagnosis was ganglioglioma. Because the tumor grew gradually in size over the next 2 years, he underwent chemotherapy with temozolomide. However, at 8 years of age, the boy developed hydrocephalus and the cystic lesion had re-grown. Endoscopic cyst fenestration and tumor biopsy was performed, and pathological diagnosis was tentatively oligodendroglioma based on the presence of tumor cells with a perinuclear halo. At 10 years of age, hydrocephalus recurred and the cystic lesion had re-grown. A second round of endoscopic cyst fenestration and tumor biopsy led to a pathological diagnosis of pilocytic astrocytoma due to a biphasic appearance with areas of dense tumor cells and microcystic areas, tumor cells with eosinophilic processes, and the presence of an eosinophilic granular body. Genetic analysis of the first biopsy successfully identified the BRAF V600E mutation. Because pathological diagnosis of diencephalic low-grade glioma harboring BRAF V600E would be sometimes difficult due to pathological variations, pathological diagnosis should be performed under the consideration of molecular diagnosis of BRAF V600E for optimal diagnosis and treatment

Distinct TERT

The majority of oligodendroglial tumors harbor mutations in the telomerase reverse transcriptase (TERT) gene (TERT) promoter and the isocitrate dehydrogenase 1/2 (IDH1/2) gene (IDH1/2), as well as 1p/19q codeletion. Generally, TERT promoter mutations, C250T and C228T, are mutually exclusive. We present a case of oligodendroglioma harboring both C250T and C228T mutations in TERT promoter. A 38-year-old man presented with grand mal seizures and underwent a resection surgery for a left frontal lobe tumor. He was pathologically diagnosed as having oligodendroglioma and was carefully observed. At 48 years of age, he underwent another resection surgery due to tumor regrowth, with the pathological diagnosis of anaplastic oligodendroglioma. Genetic analysis of the initial tumor specimen revealed IDH1 R132H mutation and both C250T and C228T mutations in TERT promoter. Using mutation-specific primers, two mutations were considered to be distributed in different alleles. In the tumor specimen obtained during the second surgery, IDH1 R132H mutation was detected to be similar to that of the initial specimen; however, only C228T mutation was detected in TERT promoter. The 1p/19q codeletion was detected in both the initial and recurrent tumor specimens. According to the sequencing data from the two tumor specimens, although TERT promoter mutation has been considered to be an early genetic event in the tumorigenesis of oligodendroglial tumors, it is likely that the C250T and C228T mutations in TERT promoter are subclonally distributed in the same tumor specimen of the present case