Aging-Related Metabolome Analysis of the Masseter Muscle in Senescence-Accelerated Mouse-Prone 8.

Frailty is a vulnerable state that marks the transition to long-term care for older people. Early detection and prevention of sarcopenia, the main symptom of frailty, are important to ensure an excellent quality of life for older people. Recently, the relationship between frailty, sarcopenia, and oral function has been attracting attention. This study aimed to clarify the changes in metabolites and metabolic pathways due to aging in the masseter muscle of senescence-accelerated mouse-prone 8 (SAMP8) mice. A capillary electrophoresis-mass spectrometry metabolome analysis was performed on the masseter muscle of 12-week-old, 40-week-old, and 55-week-old mice. The expression of enzymes involved in metabolome pathways considered to be related to aging was confirmed using reverse transcription polymerase chain reaction. Clear metabolic fluctuations were observed between 12, 40-week-old, and 55-week-old SAMP8 mice. The extracted metabolic pathways were the glycolysis, polyamine metabolome, and purine metabolome pathways. Nine fluctuated metabolites were common among the groups. Spermidine and Val were increased, which was regarded as a characteristic change in the masseter muscle due to aging. In conclusion, the age-related metabolic pathways in SAMP8 mice were the glycolysis, polyamine metabolome, and purine metabolome pathways. The increased spermidine and Val levels in the masseter muscle compared with the lower limbs are characteristic changes.

Staged Regenerative-Phenotype Modification Therapy for Multiple RT3 Gingival Recessions in Periodontally Compromised Anterior Mandibular Teeth: A Case Report.

We report the successful treatment of multiple recession type (RT) 3 gingival recessions in periodontally compromised mandibular anterior teeth with limited keratinized tissue. A 35-yearold man with stage III, grade C periodontitis underwent a two-stage intervention. Initially, a modification of the connective tissue graft (m-CTG) wall technique was used as part of phenotype modification therapy. The CTG acted as a protective 'wall,' securing space for periodontal regeneration, enhancing root coverage, soft tissue thickness, and keratinized mucosal width. Recombinant human fibroblast growth factor-2 and carbonate apatite promoted periodontal regeneration. This procedure successfully facilitated periodontal regeneration, resulting in the transition from RT3 to RT2 gingival recession and adequate keratinized mucosal width. Eighteen months later, the second surgery used a tunneled coronally advanced flap (TCAF) for root coverage. TCAF involved combining a coronally advanced flap and tunnel technique by elevating the trapezoidal surgical papilla and using a de-epithelialized CTG inserted beneath the tunneled flap. Root conditioning with ethylenediaminetetraacetic acid and enamel matrix derivative gel application were performed. Consequently, mean CAL gain was 5.3 mm, mean root coverage was 4.5 mm in height, and the gingival phenotype improved at the treated sites by the 12-month follow-up. This staged approach addresses the challenges of treating RT3 gingival recession with promising outcomes.

Entire Papilla Preservation Technique with Recombinant Human Fibroblast Growth Factor-2 and Autogenous Bone Grafting in the Treatment of Isolated Non-Contained Intrabony Defect: Case Report of a 5-Year Follow-Up.

Regenerative periodontal surgery is an effective procedure for the treatment of intrabony defects. Various flap designs preserving the defect-associated interdental papilla have been proposed to improve early wound stability. This case report describes the long-term results of a regenerative treatment in severely compromised mandibular canine using entire papilla preservation technique. Surgical access was provided by a single buccal vertical incision without any papilla incision. Combination of autogenous bone harvested from the same surgical site and recombinant human fibroblast growth factor-2 was applied to non-contained intrabony defect following the granulation tissue removal. Surgical site was closed with single interrupted sutures. The clinical outcomes and 5-year stability of pocket closure with no increase in gingival recession show the potential of entire papilla preservation technique with the use of combined biomaterials.

The Apical Tooth Replantation with Surgical Intrusion Technique (ATR-SIT) for Regenerative Treatment of Hopeless Teeth: A Report of Two Cases.

The aim of the present clinical report is to introduce a novel surgical procedure, the 'Apical Tooth Replantation with Surgical Intrusion Technique' (ATR-SIT) for managing teeth with hopeless prognosis compromised with a severe endodontal-periodontal lesion, pathologic tooth migration, and gingival recession. Two cases are presented managing teeth diagnosed with a hopeless prognosis. ATR-SIT involves tooth extraction, extra-oral root debridement, root surface conditioning, apicectomy, retrograde filling and the application of enamel matrix derivatives prior to reimplantation. Following reimplantation, the teeth are covered with a combination of autogenous bone chips and bone substitute materials, covered with resorbable membranes. Following ATR-SIT, the patients received either orthodontic treatment or tooth-supported fixed dental prostheses. The described ATR-SIT effectively improved the initially hopeless prognosis of the teeth and maintained periodontal health over time, evidenced by favourable clinical and radiographic outcomes. ATR-SIT might be a potential alternative to tooth extraction of hopeless teeth in patients with stage IV periodontitis.

Beneficial effects of a new neuroprotective compound in neuronal cells and MPTP-administered mouse model of Parkinson's disease.

A new compound, a derivative of 3,4,5-trimethoxy-N-phenyl benzamide bearing an 8''-methylimidazopyridine moiety, is found to demonstrate neuroprotective effects by preventing cell death caused by oxidative stress. The compound possesses high solubility and metabolic stability, and inhibits MPTP-induced effects in vivo, indicating high potential as a therapeutic drug for Parkinson's disease.

Double-sided entire papilla preservation technique in the combination periodontal regenerative therapy: A case report.

BACKGROUND: With the entire papilla preservation (EPP) technique, it is possible to perform regenerative therapy without incisions in the interdental papilla and to reduce the risk of papillary rupture. However, one limitation of the EPP is the sole access from the buccal side. Here, we present a case of periodontitis treated by the combination regenerative therapy employing the Double-sided (buccal-palatal) EPP (DEPP) technique, which adds a palatal vertical incision to the EPP. METHODS: A patient with 1-2 wall intrabony defects received the regenerative therapy using recombinant human fibroblast growth factor (rhFGF)-2 and carbonate apatite (CO3 Ap). Using the DEPP technique, vertical incisions at buccal and palatal aspects were placed to gain adequate access to the 1-2 wall intrabony defects between #11 and #12 without incision in the interdental papilla. After debridement, rhFGF-2 and CO3 Ap were applied to the defect. Periodontal clinical parameters and radiographic images were evaluated at the first visit, following initial periodontal therapy (baseline), 6, 9, and 12 months postoperatively. RESULTS: Wound healing was uneventful. Scarring of the incision lines was minimal. At 12 months postoperatively, probing depth reduction was 4 mm, clinical attachment gain was 4 mm, and gingival recession was not observed. An improvement in radiopacity in the previous bone defect was observed. CONCLUSION: The DEPP is an innovative technique that allows approaching from both the buccal and palatal sides while ensuring flap extensibility without compromising the interdental papilla. This report suggests that the combination of regenerative therapy with the DEPP may be promising in the treatment of intrabony defects. KEY POINTS: Why is this case new information? The DEPP allows a direct visual approach to a 1-2 wall intrabony defect extending from the buccal to palatal sides, and increases flap extensibility, without compromising the papilla. What are the keys to the successful management of this case? Assessment of three-dimensional bone defect morphology is required. Computed tomography images are very useful. The flap elevation just under the interdental papilla should be carefully performed with a small excavator to avoid damage to the interdental papilla. What are the primary limitations to success in this case? Despite the addition of a palatal incision, it was not possible to obtain complete flexibility of the palatal gingiva. Caution must be taken in a case in which the distance between the interdental papilla is narrow. Even if the interdental papilla is ruptured during the operation, recovery is possible by continuing the operation and suturing the rupture at the end.

Supra-Alveolar Periodontal Tissue Reconstruction in a Case with Severe Periodontitis: Case Report with a 2-Year Follow-up.

Periodontal regeneration therapy has developed tremendously since its inception, becoming a clinical tool to preserve the periodontally compromised natural dentition. More challenging esthetic defects can often benefit from the combination of bone and soft tissue regeneration, such as the application of connective tissue grafts (CTGs) and techniques that approach the bone defect without interdental papillae incisions. However, periodontal tissue regeneration vertical to the alveolar bone crest in cases of severe periodontitis, with loss of both soft and hard tissues, has not been predictably established. This case report describes a patient with severe periodontitis that was treated with in supra-alveolar periodontal tissue reconstruction. This innovative surgical technique requires both horizontal buccal incisions and several vertical palatal incisions, avoiding the interdental papillae on the periodontal defect. Then, a space is created by suspending and fixating the flap coronally, and CTG and regenerative materials (such as recombinant human fibroblast growth factor-2) and bone graft material are applied. This technique has the potential to gain clinical attachment, achieve supra-/intraperiodontal regeneration, and enhance esthetic outcomes, including a reduced gingival recession and interdental papillae reconstruction. The clinical results of the present case were well maintained over the 2-year follow-up. Int J Periodontics Restorative Dent 2023;43:213-221. doi: 10.11607/prd.6241.

Optic nerve-associated connective tissue structures revisited: A histological study using human fetuses and adult cadavers.

Unlike the usual peripheral nerve, the optic nerve accompanies a thick "dural sheath," a thin "sheath of pia mater" (SPM), and multiple "septa," which divides the nerve fibers into fascicles. We collected specimens from 25 adult cadavers and 15 fetuses and revisited the histological architecture of the optic and oculomotor nerves. In the optic chiasma, the meningeal layer of the dura joins the pia to form a thick SPM, and the periosteum of the sphenoid is continuous with the dural sheath at the orbital exit of the bony optic canal. The septa appeared as a cluster of irregularly arrayed fibrous plates in the intracranial course near the chiasma. Thus, the septa were not derived from either the SPM or the dural sheath. In the orbit, the central artery of the retina accompanies collagenous fibers from the dural sheath and the SPM to provide the vascular sheath in the optic nerve. These connective tissue configurations were the same between adult and fetal specimens. At the optic disk, the dural sheath and SPM merged with the sclera, whereas the septa appeared to end at the lamina cribrosa. However, in fetuses without lamina cribrosa, the septa extend into the nerve fiber layer of the retina. The SPM and septa showed strong elastin immunoreactivity, in contrast to the absence of reactivity in the sheaths of the oculomotor nerve. Each S100 protein-positive Schwann sheath of the oculomotor nerve was surrounded by collagenous endoneurium. Glial fibrillary acidic protein-positive astrocytes showed a linear arrangement along the septa.

Development and Regeneration of Muscle, Tendon, and Myotendinous Junctions in Striated Skeletal Muscle.

Owing to a rapid increase in aging population in recent years, the deterioration of motor function in older adults has become an important social problem, and several studies have aimed to investigate the mechanisms underlying muscle function decline. Furthermore, structural maintenance of the muscle-tendon-bone complexes in the muscle attachment sites is important for motor function, particularly for joints; however, the development and regeneration of these complexes have not been studied thoroughly and require further elucidation. Recent studies have provided insights into the roles of mesenchymal progenitors in the development and regeneration of muscles and myotendinous junctions. In particular, studies on muscles and myotendinous junctions have-through the use of the recently developed scRNA-seq-reported the presence of syncytia, thereby suggesting that fibroblasts may be transformed into myoblasts in a BMP-dependent manner. In addition, the high mobility group box 1-a DNA-binding protein found in nuclei-is reportedly involved in muscle regeneration. Furthermore, studies have identified several factors required for the formation of locomotor apparatuses, e.g., tenomodulin (Tnmd) and mohawk (Mkx), which are essential for tendon maturation.

Localization of T-cell factor 4 positive fibroblasts and CD206-positive macrophages during skeletal muscle regeneration in mice.

Skeletal muscle regeneration is initiated by the activation of the transcription factor paired box 7 (Pax7), which is expressed in the satellite cells. The nuclear transcription factor T-cell factor 4 (Tcf4) is expressed in the fibroblasts and is involved in muscle tissue repair, while M2-like macrophages play an important role in skeletal muscle regeneration. However, the localization of M2-like macrophages and the expression of Tcf4 over a period of time during skeletal muscle regeneration remain unknown. Therefore, the murine masseter muscle was immunofluorescence investigated for the surface protein CD206 of M2-like macrophages and Tcf4 of fibroblasts during skeletal muscle regeneration to understand the changes in the CD206 and Tcf4 expression over time. We observed that CD206 entered the cytoplasm of some regenerating muscle fibers 5-7 days after the experimental muscle damage, that is, in the early stage of maturation of the regenerating muscle fibers with central nuclei. In addition, Tcf4 was expressed in the nuclei of the fibroblasts around the regenerating muscle fibers and in the central nuclei of the regenerating muscle fibers. Furthermore, the expression of laminin adjacent to Tcf4-positive cells was observed to partially disappear, and the shape of this missing part was observed to be identical to that of the nuclei of Tcf4-positive cells adjacent to the laminin. Clathrin was also expressed in these sites, demonstrating endocytosis. Thus, these results suggest that in the early stage of maturation of the regenerating muscle fibers, M2-like macrophages and Tcf4-positive fibroblasts enter the cytoplasm of the regenerating muscle fibers, thereby regulating the expression of various maturation factors.

Interleukin-4 Receptor α Subunit Deficiency Alleviates Murine Intestinal Inflammation In Vivo Through the Enhancement of Intestinal Mucosal Barrier Function.

Disturbance of epithelial barrier function causes chronic intestinal inflammation such as inflammatory bowel disease. Several studies have reported that Th2 cytokines such as interleukin (IL)-4 and IL-13 play an important role in the regulation of intestinal barrier function. However, the precise role of the IL-4 receptor α subunit (IL-4Rα) in intestinal inflammation remains unclear. Thus, we used an experimental colitis model to investigate the role of IL-4Rα in intestinal inflammation. IL-4Rα-deficient (IL-4Rα-/-) mice and their littermate wild-type (WT) mice were used. Experimental colitis was induced by administration of 3% dextran sulfate sodium (DSS) in the drinking water for seven days. Treatment with DSS caused body weight loss, an increase in the disease activity index and histological abnormalities in WT colitis mice, all of which were significantly attenuated in IL-4Rα-/- colitis mice. Neutrophil infiltration in the colonic mucosa was reduced in IL-4Rα-/- colitis mice compared with WT colitis mice. NADPH oxidase 1 expression and reactive oxygen species production were increased in the colons of IL-4Rα-/- mice. Furthermore, elevated intestinal permeability induced by DSS treatment was suppressed in IL-4Rα-/- colitis mice. These results demonstrate that IL-4Rα-/- mice exhibit reduced susceptibility to DSS-induced colitis. Our present findings suggest that IL-4Rα deficiency enhances intestinal mucosal barrier function through the upregulation of NADPH oxidase 1-dependent reactive oxygen species production, thereby suppressing the development of intestinal inflammation.

Accelerated Wound Healing on Skin by Electrical Stimulation with a Bioelectric Plaster.

Wound healing on skin involves cell migration and proliferation in response to endogenous electric current. External electrical stimulation by electrical equipment is used to promote these biological processes for the treatment of chronic wounds and ulcers. Miniaturization of the electrical stimulation device for wound healing on skin will make this technology more widely available. Using flexible enzymatic electrodes and stretchable hydrogel, a stretchable bioelectric plaster is fabricated with a built-in enzymatic biofuel cell (EBFC) that fits to skin and generates ionic current along the surface of the skin by enzymatic electrochemical reactions for more than 12 h. To investigate the efficacy of the fabricated bioelectric plaster, an artificial wound is made on the back skin of a live mouse and the wound healing is observed for 7 d in the presence and absence of the ionic current of the bioelectric plaster. The time course of the wound size as well as the hematoxylin and eosin staining of the skin section reveals that the ionic current of the plaster leads to faster and smoother wound healing. The present work demonstrates a proof of concept for the electrical manipulation of biological functions by EBFCs.

Intrinsically Stretchable Electrochromic Display by a Composite Film of Poly(3,4-ethylenedioxythiophene) and Polyurethane.

A stretchable, electrochromic film of a uniform composite of poly(3,4-ethylenedioxythiophene):p-toluene sulfonic acid (PEDOT:PTS) and polyurethane (PU) (PEDOT/PU) was fabricated, and its integration with a hydrogel as a free-standing, stretchable electrochromic (EC) display was demonstrated. The PEDOT/PU composite film was prepared by the spin coating of a solution containing an EDOT monomer and PU, followed by oxidative polymerization using iron(III) tosylate at elevated temperature. The fabricated film showed reversible electrochromism without an external conductive support. The color change of the film can be used to quantify the progress of the redox reactions by means of digital camera image analysis and a custom mobile phone app.

Design and Experimental Verification of a 0.19 V 53 µW 65 nm CMOS Integrated Supply-Sensing Sensor With a Supply-Insensitive Temperature Sensor and an Inductive-Coupling Transmitter for a Self-Powered Bio-sensing System Using a Biofuel Cell.

In this paper, we present a self-powered bio-sensing system with the capability of proximity inductive-coupling communication for supply sensing and temperature monitoring. The proposed bio-sensing system includes a biofuel cell as a power source and a sensing frontend that is associated with the CMOS integrated supply-sensing sensor. The sensor consists of a digital-based gate leakage timer, a supply-insensitive time-domain temperature sensor, and a current-driven inductive-coupling transmitter and achieves low-voltage operation. The timer converts the output voltage from a biofuel cell to frequency. The temperature sensor provides a pulse width modulation (PWM) output that is not dependent on the supply voltage, and the associated inductive-coupling transmitter enables proximity communication. A test chip was fabricated in 65 nm CMOS technology and consumed 53 µW with a supply voltage of 190 mV. The low-voltage-friendly design satisfied the performance targets of each integrated sensor without any trimming. The chips allowed us to successfully demonstrate proximity communication with an asynchronous receiver, and the measurement results show the potential for self-powered operation using biofuel cells. The analysis and experimental verification of the system confirmed their robustness.

Stretchable biofuel cell with enzyme-modified conductive textiles.

A sheet-type, stretchable biofuel cell was developed by laminating three components: a bioanode textile for fructose oxidation, a hydrogel sheet containing fructose as fuel, and a gas-diffusion biocathode textile for oxygen reduction. The anode and cathode textiles were prepared by modifying carbon nanotube (CNT)-decorated stretchable textiles with fructose dehydrogenase (FDH) and bilirubin oxidase (BOD), respectively. Enzymatic reaction currents of anode and cathode textiles were stable for 30 cycles of 50% stretching, with initial loss of 20-30% in the first few cycles due to the partial breaking of the CNT network at the junction of textile fibers. The assembled laminate biofuel cell showed power of ~0.2 mW/cm(2) with 1.2 kΩ load, which was stable even at stretched, twisted, and wrapped forms.

Organic transdermal iontophoresis patch with built-in biofuel cell.

A completely organic iontophoresis patch is reported. A built-in biofuel cell is mounted on the patch that generates transdermal iontophoretic administration of compounds into the skin. The amplitude of transdermal current is tuned by integrating a conducting polymer-based stretchable resistor of predetermined resistance.

Surfactant-assisted direct electron transfer between multi-copper oxidases and carbon nanotube-based porous electrodes.

The effects of pre-treatment with surfactants on the electrocatalytic reaction of multi-copper oxidases were quantitatively evaluated using a well-structured carbon nanotube forest electrode. It was found that both the charge polarity of the head group and the aromatics in the tail part of the surfactants affect the efficiency of enzymatic electrocatalysis.

Dynamic characteristics of the middle ear in neonates.

OBJECTIVE: Early diagnosis and treatment of hearing disorders in neonates is highly effective for realization of linguistic competence and intellectual development. To objectively and quickly evaluate the dynamic characteristics of the middle ear, a sweep frequency impedance (SFI) meter was developed, which allowed the diagnosis of middle-ear dysfunctions in adults and children. However, this SFI meter was not applicable to neonates since the size of the measurement probe was too large. In the present study, therefore, the SFI meter was improved, i.e., the diameter of the probe was reduced to that of the neonatal external ear canal. By using this newly designed SFI meter, SFI tests were performed in healthy neonates. METHODS: A sound of the sweeping sinusoidal frequency between 0.1 kHz and 2.0 kHz in 0.02-kHz step intervals is presented to the ear canal by an SFI probe while the static pressure of the ear canal is kept constant. During this procedure, the sound pressure level (SPL) is measured. The measurements are performed at 50-daPa intervals of static pressure from 200 daPa to -200 daPa. RESULTS: Measurements were conducted in 10 ears of 9 neonates. The SPL showed two variations at 0.26 ± 0.03 kHz and 1.13 ± 0.12 kHz. Since the SPL is known to show a variation at frequencies from 1.0 kHz to 1.6 kHz due to the resonance of the middle ear in adults and children with normal hearing, the second variation is probably related to such resonance in neonates. The measurement of gel models, which mimics the neonatal external ear canal, showed a variation in SPL at around 0.5 kHz. This implies that the source of the first variation may possibly be related to the resonance of the external ear canal wall. CONCLUSIONS: SFI tests revealed that there were two variations in the SPL curve in neonates, one at 0.26 ± 0.03 kHz and the other at 1.13 ± 0.12 kHz, the former and the latter being possibly related to the resonance of the external ear canal wall and that of the middle ear, respectively. This result suggests that the dynamic characteristics of the middle ear in neonates are different from those in adults.