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Constitutive NF‐κB activation is associated with cellular senescence and stem cell dysfunction and rare variants in NF‐κB family members are enriched in centenarians. We recently identified a novel small molecule (SR12343) that inhibits IKK/NF‐κB activation by disrupting the association between IKKβ and NEMO. Here we investigated the therapeutic effects of SR12343 on senescence and aging in three different mouse models. SR12343 reduced senescence‐associated beta‐galactosidase (SA‐β‐gal) activity in oxidative stress‐induced senescent mouse embryonic fibroblasts as well as in etoposide‐induced senescent human IMR90 cells. Chronic administration of SR12343 to the Ercc1 −/ ∆ and Zmpste24 −/− mouse models of accelerated aging reduced markers of cellular senescence and SASP and improved multiple parameters of aging. SR12343 also reduced markers of senescence and increased muscle fiber size in 2‐year‐old WT mice. Taken together, these results demonstrate that IKK/NF‐κB signaling pathway represents a promising target for reducing markers of cellular senescence, extending healthspan and treating age‐related diseases., Constitutive IKK/NF‐κB activation is associated with cellular senescence and aging. Here we demonstrate that pharmacological inhibition of IKK/NF‐κB activation by the small molecule SR12343 reduced senescence and SAPS factors in cell culture, improved healthspan in mice with accelerated aging, and reduced markers of senescence and pathology in multiple tissues of both accelerated and naturally aged mice. Therefore, IKK/NF‐κB pathway is a promising target for aging interventions to treat age‐related diseases.

Objective The aim of this study was to evaluate the biomechanical properties of three different miniature locking plate systems used to fixate radial and ulnar fractures in toy breed dogs. Implant size, shape, material and locking systems differ, and their influence on the fracture healing process is unknown. In the present study, we aimed to investigate this matter in vivo using rabbit radial and ulnar fracture models. Study Design Eighteen rabbits were randomly divided into three groups, and the left radius and ulna were osteotomized to create fracture models. The osteotomies were then fixated using either the TITAN LOCK 1.5, Fixin micro or LCP 1.5 system. Radiographs were obtained 2, 3 and 4 weeks after surgery. Four weeks after surgery, the radiuses were collected and used for biomechanical testing or histological examinations. Results During the 4 weeks of observation, no adverse effects due to the implants occurred. The radiographic scores in each group did not differ significantly at any time point. The maximum load in the LCP group was significantly higher than that in the TITAN and Fixin groups. There was no significant difference in bending stiffness or work to failure among the groups. Initial fracture healing via woven bone was evident at histological evaluation. Conclusions All three miniature locking plate systems provided adequate fracture stabilization 4 weeks after surgery, despite their differences, in rabbit models.

The bone regeneration capacities of calcium phosphate (CaP)-loaded carboxymethyl cellulose (CMC) nonwoven sheet (CMC/CaP) were evaluated using a dog lateral femoral condyle defect model. In addition, the effect of bFGF on bone regeneration when added to CMC/CaP sheet was investigated. The CMC and CMC/CaP sheets have high operability. The new bone formation rate in the CMC/CaP group was significantly higher than that in the control and CMC groups based on micro-computed tomography and histological evaluation. In contrast, there was no significant difference between the CMC/CaP group and the CMC/CaP/f group. In conclusion, the CMC/CaP sheet has the ability to promote new bone formation and seems to be useful as a sheet-shaped bone graft substitute. The effect of the auditioning signaling molecules to the CMC/CaP sheet, such as bFGF, requires further investigation. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1516-1521, 2019.

In the present study we investigated whether xaliproden, a selective 5-HT1A receptor agonist, could relieve allodynia induced by three types of chemotherapeutic agents (paclitaxel, vincristine, and oxaliplatin) in mice. A single intraperitoneal injection of paclitaxel (5mg/kg), vincristine (0.1mg/kg), or oxaliplatin (3mg/kg) time-dependently increased punctate stimulation-evoked allodynia over 10-14 days; the intensities of allodynia were similar between the treatment groups. A single oral dose of xaliproden (0.3-3mg/kg) inhibited paclitaxel-induced allodynia in a dose-dependent manner. Xaliproden (3mg/kg) administration produced a slight and no suppression of vincristine-induced and oxaliplatin-induced allodynia, respectively. The firing response of the tibial nerve to punctate stimulation increased in mice that received paclitaxel or oxaliplatin. Xaliproden (3mg/kg) markedly inhibited the firing response in the mice treated with paclitaxel, while it partially inhibited the firing response in the oxaliplatin-treated animals. Vincristine did not significantly increase the tibial nerve response. Paclitaxel significantly increased the mRNA expression of 5-HT1A receptor in the dorsal root ganglia, but not in the spinal dorsal horn. In contrast, oxaliplatin significantly increased the mRNA expression of 5-HT1A receptor in the spinal dorsal horn, but not in the dorsal root ganglia. Vincristine did not affect the mRNA expression of 5-HT1A receptor in both these regions. These results suggest that xaliproden produces acute inhibition of mechanical allodynia induced by paclitaxel, but not by vincristine and oxaliplatin, via inhibition of the hyper-response of the primary afferent neurons.

The aim of this study was to detect the differences in muscle metabolic response of the quadriceps during incremental dynamic knee exercise using regional (31)Phosphorus Chemical Shift Imaging ((31)P-CSI). Sixteen healthy men participated in this study (age 28 ± 5 years, height 171.4 ± 3.9 cm, weight 67.1 ± 9.8 kg). The experiments were carried out with a 1.5-T superconducting magnet with a 5-in. diameter circular surface coil. The subjects performed isometric unilateral knee extension exercise to detect their maximum voluntary contraction (MVC) in prone position. Then they performed dynamic unilateral knee extension exercise in the magnet at 10, 20, 30 and 40 % of their MVC with the transmit-receive coil placed under the right quadriceps. The subjects pulled down a rope with the adjusted weight attached to the ankle at a frequency of 0.5 Hz for 380 s. Intracellular pH (pHi) was calculated from the median chemical shift of the inorganic phosphate (Pi) peak relative to phosphocreatine (PCr). The quadriceps were divided into three regions, (1) medial, (2) anterior, (3) lateral, and in comparison, there was no significant difference in Pi/PCr nor in pHi between regions, except Pi/PCr of the medial region was significantly higher than the anterior region at maximum intensity (p 0.05). These results suggest that regional muscle metabolic response is similar in the quadriceps except at maximum intensity.

Muscle tissue oxygenation is a critical issue in muscle complications such as pain, exhaustion, stiffness, or fatigue during and after exercise. The aim of this study was to investigate whether the changes of muscle tissue oxygenation could be observed at both erector spinae muscle at S1 level and gastrocnemius during and after acupuncture stimulation to ipsilateral erector spinae at S1 level. The subjects were ten healthy males. Muscle oxygenation was monitored by near infrared spectroscopy (NIRS), and the probes were placed on the right side of the erector spinae muscle at S1 level (Guanyuanshu, BL26) and the belly of the gastrocnemius on the right (Chengjin, BL56). The subjects lay on the bed in prone position for 10 min, followed by acupuncture insertion into the right side of BL26. The needle was left for 10 min and subjects were kept still for 10 min after removal. At BL26, oxygenated-hemoglobin (oxy-Hb) was significantly increased compared to the baseline at 10 min after insertion (p 0.05), then continued increasing. Total hemoglobin (t-Hb) was increased at 2 min after removal (p 0.05). Tissue-oxygen saturation (StO2) was increased at 7 min after insertion (p 0.05). At BL56, oxy-Hb and t-Hb were increased at 6 and 2 min after removal, respectively (p 0.05). StO2 showed no significant change. The acupuncture stimulation affected muscle tissue oxygenation differently at both stimulated and non-stimulated points in the same innervation.

Previous studies have reported significant region-dependent differences in the fiber-type composition of human skeletal muscle. It is therefore hypothesized that there is a difference between the deep and superficial parts of muscle energy metabolism during exercise. We hypothesized that the inorganic phosphate (Pi)/phosphocreatine (PCr) ratio of the superficial parts would be higher, compared with the deep parts, as the work rate increases, because the muscle fiber-type composition of the fast-type may be greater in the superficial parts compared with the deep parts. This study used two-dimensional 31Phosphorus Chemical Shift Imaging (31P-CSI) to detect differences between the deep and superficial parts of the human leg muscles during dynamic knee extension exercise. Six healthy men participated in this study (age 27±1 year, height 169.4±4.1 cm, weight 65.9±8.4 kg). The experiments were carried out with a 1.5-T superconducting magnet with a 5-in. diameter circular surface coil. The subjects performed dynamic one-legged knee extension exercise in the prone position, with the transmit-receive coil placed under the right quadriceps muscles in the magnet. The subjects pulled down an elastic rubber band attached to the ankle at a frequency of 0.25, 0.5 and 1 Hz for 320 s each. The intracellular pH (pHi) was calculated from the median chemical shift of the Pi peak relative to PCr. No significant difference in Pi/PCr was observed between the deep and the superficial parts of the quadriceps muscles at rest. The Pi/PCr of the superficial parts was not significantly increased with increasing work rate. Compared with the superficial areas, the Pi/PCr of the deep parts was significantly higher (p0.05) at 1 Hz. The pHi showed no significant difference between the two parts. These results suggest that muscle oxidative metabolism is different between deep and superficial parts of quadriceps muscles during dynamic exercise.

The chemotherapeutic agent oxaliplatin induces neuropathic pain, a dose-limiting side effect, but the underlying mechanisms are not fully understood. Here, we show the potential involvement of cutaneous mast cells in oxaliplatin-induced mechanical allodynia in mice. A single intraperitoneal injection of oxaliplatin induced mechanical allodynia, which peaked on day 10 after injection. Oxaliplatin-induced mechanical allodynia was almost completely prevented by congenital mast cell deficiency. The numbers of total and degranulated mast cells was significantly increased in the skin after oxaliplatin administration. Repetitive topical application of the mast cell stabilizer azelastine hydrochloride inhibited mechanical allodynia and the degranulation of mast cells without affecting the number of mast cells in oxaliplatin-treated mice. The serine protease inhibitor camostat mesilate and the proteinase-activated receptor 2 (PAR2) antagonist FSLLRY-NH2 significantly inhibited oxaliplatin-induced mechanical allodynia. However, it was not inhibited by the H1 histamine receptor antagonist terfenadine. Single oxaliplatin administration increased the activity of cutaneous serine proteases, which was attenuated by camostat and mast cell deficiency. Depletion of the capsaicin-sensitive primary afferents by neonatal capsaicin treatment almost completely prevented oxaliplatin-induced mechanical allodynia, the increase in the number of mast cells, and the activity of cutaneous serine proteases. These results suggest that serine protease(s) released from mast cells and PAR2 are involved in oxaliplatin-induced mechanical allodynia. Therefore, oxaliplatin may indirectly affect the functions of mast cells through its action on capsaicin-sensitive primary afferents.

【目的】国体セーリング競技会場に設置したコンディショニングルームでセーリング選手の身体愁訴に対する鍼治療の直後効果を検討したので報告する。【方法】腰部の筋痛 (n=108) 、頚肩背部の筋痛 (n=72) に鍼治療を単独で行った。鍼治療は局所治療とした。調査項目は主訴およびその程度を示すVAS値とした。VAS値の有意差検定は対応のあるt検定とした。【結果】主訴は腰痛、頚肩背痛、その他の順に多かった。鍼治療は腰部の筋痛 (n=108) のVAS値を治療前53.2±21.5mmから後21.5±16.4mmに減少 (p

A tandem structure was introduced to improve the spectral response of dye-sensitized solar cells (DSC) without loosing their high external quantum yield. Light absorption models of DSC were proposed, and light harvesting efficiency (LHE) and incident photon-to-current conversion efficiency (IPCE) were calculated using absorption spectra of dye-adsorbed TiO 2 electrode, electrolyte, and conducting glass support. The IPCE of single DSCs fabricated using two typical ruthenium complexes were measured to present the improvement of the spectral response without loosing their high external quantum yield by tandem structure. As a result, the tandem structured cell exhibited higher photocurrent and conversion efficiency than each single DSC mainly caused from its extended spectral response.

【目的】肩こりに及ぼす円皮鍼 (PTN) の効果をプラセボ円皮鍼 (P) を対照とした臨床試験 (CCT) で検討した。【対象及び方法】肩こりを有するボランティア男女合計53名を対象にした。PTNもしくはPの施術部位は後頚部、肩上部、肩甲間部の圧痛点で、3日間継続留置した。評価は3日後の肩こりの自覚及び施術前、施術直後、3日後の肩こり程度のVAS値とした。【結果】「肩こりがある」はP群25名中23例に対しPTN群は28名中12例に減少 (p

In the present study we investigated whether xaliproden, a selective 5-HT1A receptor agonist, could relieve allodynia induced by three types of chemotherapeutic agents (paclitaxel, vincristine, and oxaliplatin) in mice. A single intraperitoneal injection of paclitaxel (5mg/kg), vincristine (0.1mg/kg), or oxaliplatin (3mg/kg) time-dependently increased punctate stimulation-evoked allodynia over 10-14 days; the intensities of allodynia were similar between the treatment groups. A single oral dose of xaliproden (0.3-3mg/kg) inhibited paclitaxel-induced allodynia in a dose-dependent manner. Xaliproden (3mg/kg) administration produced a slight and no suppression of vincristine-induced and oxaliplatin-induced allodynia, respectively. The firing response of the tibial nerve to punctate stimulation increased in mice that received paclitaxel or oxaliplatin. Xaliproden (3mg/kg) markedly inhibited the firing response in the mice treated with paclitaxel, while it partially inhibited the firing response in the oxaliplatin-treated animals. Vincristine did not significantly increase the tibial nerve response. Paclitaxel significantly increased the mRNA expression of 5-HT1A receptor in the dorsal root ganglia, but not in the spinal dorsal horn. In contrast, oxaliplatin significantly increased the mRNA expression of 5-HT1A receptor in the spinal dorsal horn, but not in the dorsal root ganglia. Vincristine did not affect the mRNA expression of 5-HT1A receptor in both these regions. These results suggest that xaliproden produces acute inhibition of mechanical allodynia induced by paclitaxel, but not by vincristine and oxaliplatin, via inhibition of the hyper-response of the primary afferent neurons.