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Resistance exercise provides significant benefits to skeletal muscle, including hypertrophy and metabolic enhancements, supporting overall health and disease management. However, skeletal muscle responsiveness to resistance exercise is significantly reduced in conditions such as aging and diabetes. Recent reports suggest that glycation stress contributes to muscle atrophy and impaired exercise-induced muscle adaptation; however, its role in the muscle response to resistance exercise remains unclear. Therefore, in this study, we investigated whether methylglyoxal (MGO), a key factor in glycation stress, affects the acute responsiveness of skeletal muscles to resistance exercise, focusing on protein synthesis and the key signaling molecules. This study included 12 8-week-old male Sprague-Dawley rats divided into two groups: one received 0.5% MGO-supplemented drinking water (MGO group) and the other received regular water (control group). After 10 weeks, the left tibialis anterior muscle of each rat was subjected to electrical stimulation (ES) to mimic resistance exercise, with the right muscle serving as a non-stimulated control. Muscle protein-synthesis rates were evaluated with SUnSET, and phosphorylation levels of key signaling molecules (p70S6K and S6rp) were quantified using western blotting. In the control group, stimulated muscles exhibited significantly increased muscle protein synthesis and phosphorylation levels of p70S6K and S6rp. In the MGO group, these increases were attenuated, indicating that MGO treatment suppresses the adaptive response to resistance exercise. MGO diminishes the skeletal muscle's adaptive response to ES-simulated resistance exercise, affecting both muscle protein synthesis and key signaling molecules. The potential influence of glycation stress on the effectiveness of resistance exercise or ES emphasizes the need for individualized interventions in conditions of elevated glycation stress, such as diabetes and aging., Competing Interests: Declarations Ethical approval We confirm that we have read the journal’s position on issues involved in the ethical publication and affirm that this report is consistent with those guidelines. Competing interests The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Viral outbreaks, which include the ongoing coronavirus disease 2019 (COVID-19) pandemic provoked by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are a major global crisis that enormously threaten human health and social activities worldwide. Consequently, the rapid and repeated treatment and isolation of these viruses to control their spread are crucial to address the COVID-19 pandemic and future epidemics of novel emerging viruses. The application of cost-efficient, rapid, and easy-to-operate detection devices with miniaturized footprints as a substitute for the conventional optic-based polymerase chain reaction (PCR) and immunoassay tests is critical. In this context, semiconductor-based electrical biosensors are attractive sensing platforms for signal readout. Therefore, this study aimed to examine the electrical sensing of patient-derived SARS-CoV-2 samples by harnessing the activity of DNA aptamers directed against spike proteins on viral surfaces. We obtained rapid and sensitive virus detection beyond the Debye length limitation by exploiting aptamers coupled with alkaline phosphatases, which catalytically generate free hydrogen ions which can readily be measured on pH meters or ion-sensitive field-effect transistors. Furthermore, we demonstrated the detection of the viruses of approximately 100 copies/μL in 10 min, surpassing the capability of typical immunochromatographic assays. Therefore, our newly developed technology has great potential for point-of-care testing not only for SARS-CoV-2, but also for other types of pathogens and biomolecules., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors.)

This study aimed to investigate the effects of Brazilian propolis on body fat mass and levels of adiponectin and reactive oxygen species among community-dwelling elderly females. This was a double-blind randomized placebo-controlled trial. Altogether, 78 females aged 66-84 years were randomly assigned to the propolis (PRO; n = 39) or placebo (PLA; n = 39) group. For 12 weeks, the PRO group were given three capsules containing 227 mg of propolis twice a day. Meanwhile, the PLA group were given daily placebo capsules. Of 78 participants, 53 (PLA group: n = 28, PRO group: n = 25) completed the study. Although no changes were observed in absolute or relative fat mass in the PLA group, they showed a significant decline in the PRO group. The level of serum adiponectin in the PLA group did not change, although that of the PRO group significantly increased. The level of d-ROMs in the PLA group significantly increased, whereas that of the PRO group significantly decreased. The serum SOD activity in the PLA group significantly decreased, whereas that of the PRO group tended to increase. These results suggest that propolis supplementation may decrease body fat mass and oxidative stress among community-dwelling elderly females.

Electrical stimulation (ES) is effective for disuse-induced muscle atrophy. However, the acute effect of ES on muscle protein synthesis (MPS) and muscle protein breakdown (MPB) remains unclear. We investigated the effect of a single-session ES treatment on mTORC1 signaling, MPS, and MPB in the soleus muscle of 2-week hindlimb unloaded rats. Sprague Dawley rats (n = 12 male) were randomly divided into control (CON) and hindlimb unloaded (HU) groups. After 2 weeks, the right soleus muscle was percutaneously stimulated and underwent supramaximal isometric contractions. The left soleus muscle served as an internal control. We collected soleus muscle samples 6 h after ES. Two weeks of HU decreased p70S6K and S6rp activation, downstream factors for mTORC1 signaling, and SUnSET method-assessed MPS, but increased the LC3-II/I ratio, an indicator of autophagy. ES on disused muscle successfully activated mTORC1 signaling but did not affect MPS. Contrary, ES decreased ubiquitinated proteins expression and LC3B-II/I ratio. HU might affect mTORC1 activation and MPS differently in response to acute ES possibly due to excessive ROS production caused by ES. Our findings suggest that ES applied to disused skeletal muscles may suppress MPB, but its effect on MPS appears to be attenuated.

Oxidative stress is associated with deterioration of endurance and muscle strength, which are mostly accompanied by aging. Astaxanthin supplement has excellent antioxidant activity without any pro-oxidative properties. In this study, we investigated how astaxanthin supplementation affects walking endurance and muscle strength in nursing home residents. Healthy elderly individuals (age: 67 to 94) were divided into two groups: 13 subjects received a daily dose of 24 mg of astaxanthin for 16 weeks (astaxanthin group) and 11 subjects received a placebo (placebo group). These subjects were compared using body component measurements, serum d-ROM levels, the distance of 6-min walking, blood lactate levels after the 6-min walking test, and muscle strength. After supplementation, the levels of d-ROMs and blood lactate after the 6-min walking test in the astaxanthin group significantly decreased compared with the placebo group ( p < 0.05). Additionally, the walking distance was significantly higher in the astaxanthin group than in the placebo group ( p < 0.05), despite a significant reduction in lactate levels after 6-MWT ( p < 0.05). However, no significant intergroup differences were observed in muscle mass and strength. Astaxanthin supplement for 16 weeks is effective to increase the endurance capacity of the elderly. Astaxanthin supplement suppresses d-ROMs at rest and lactic acid production after the 6-min walk test. In contrast, astaxanthin supplement did not show significant intergroup differences in the muscle mass and strength. Therefore, the effect was most likely accompanied by an increase in endurance instead of an increase in muscle strength.

Introduction/aims: Skeletal muscle capillaries regress with disuse; however, information on time-dependent changes in the expression of pro- and anti-angiogenic factors in disused muscle is limited. This study aimed to clarify time-dependent changes in skeletal muscle capillarization, pro-angiogenic vascular endothelial growth factor-A (VEGF-A), and anti-angiogenic thrombospondin-1 (TSP-1) in the soleus muscle of hindlimb unloaded rat., Methods: Eight-week-old male Sprague Dawley rats were randomly divided into four groups corresponding to different hindlimb unloading (HU) duration at 0, 1, 2, and 3 wk., Results: Muscle atrophy and capillary regression worsened in the soleus muscle with longer periods of HU. The VEGF-A protein expression level was lower at week 1 than at week 0. In addition, the value at week 3 was also lower than those at weeks 0, 1, and 2. The TSP-1 protein expression level was higher at week 1 than that at week 0 but was similar at weeks 2 and 3. Moreover, reactive oxygen species, assessed by dihydroethidium fluorescence intensity on cryosection, were higher at weeks 2 and 3 than that at week 0., Discussion: Depending on the HU period, VEGF-A and TSP-1 showed different expression patterns. In the early HU phase, TSP-1 may play an important role in capillary regression. However, when HU extends for a longer period, decreased VEGF-A, and/or increased oxidative stress may be more involved in capillary regression., (© 2021 Wiley Periodicals LLC.)

Background: To establish a method to prevent and manage fatigue caused by psychological and physical stress in young females, early detection factors, such as understanding of fatigue and causes of psychological and physical stress, as well as a review of early management of psychiatric disease, are important. With increasing knowledge regarding the diverse causes of stress, it is important to select biomarkers with consideration of the types of stress burden and mechanisms underlying the development of physical symptoms. The methods used to search for stress characteristics is an issue that needs to be addressed. However, consensus regarding objective assessment methods for impaired mental health is lacking., Methods: We examined the effects of an objective structured clinical examination (OSCE), considered to be a uniform source of psychological and physical stress, on biomarkers of oxidative stress and fatigue in 16 third-year female medical university students (21.3 ± 2.1 years old) in Japan with a normal menstrual cycle. A self-administered questionnaire consisting of Zung's Self-rating Depression Scale (SDS) and State-Trait Anxiety Inventory (STAI) was used to assess subjective stress. Furthermore, stress-related biomarkers (urinary 8-hydroxy-2'-deoxyguanosine [u-8-OHdG], urinary 5-hydroxytryptamine [u-5-HT], and salivary human herpesvirus-6 [s-HHV-6]) were examined at 1 month, 1 week, and 1 day before, and 1 week after the OSCE., Results: The results indicated that the OSCE did not have effects on u-8-OHdG, a biomarker of oxidative stress. However, u-5-HT and s-HHV-6 were found to be elevated in examinations performed prior to the OSCE., Conclusions: The present findings suggest that u-5-HT and s-HHV-6 levels can be used for objective assessment of mental and physical fatigue in young females, including that produced not only by knowledge regarding an upcoming OSCE, but also by skill and attitude aspects related to that examination., Competing Interests: Declaration of Conflicting Interests: : The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

Aptamers can control the biological functions of enzymes, thereby facilitating the development of novel biosensors. While aptamers that inhibit catalytic reactions of enzymes were found and used as signal transducers to sense target molecules in biosensors, no aptamers that amplify enzymatic activity have been identified. In this study, we report G-quadruplex (G4)-forming DNA aptamers that upregulate the peroxidase activity in myoglobin specifically for luminol. Using in vitro selection, one G4-forming aptamer that enhanced chemiluminescence from luminol by myoglobin's peroxidase activity was discovered. Through our strategy-in silico maturation, which is a genetic algorithm-aided sequence manipulation method, the enhancing activity of the aptamer was improved by introducing mutations to the aptamer sequences. The best aptamer conserved the parallel G4 property with over 300-times higher luminol chemiluminescence from peroxidase activity more than myoglobin alone at an optimal pH of 5.0. Furthermore, using hemin and hemin-binding aptamers, we demonstrated that the binding property of the G4 aptamers to heme in myoglobin might be necessary to exert the enhancing effect. Structure determination for one of the aptamers revealed a parallel-type G4 structure with propeller-like loops, which might be useful for a rational design of aptasensors utilizing the G4 aptamer-myoglobin pair., (© The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Background: The beneficial effect of exercise combined with licorice flavonoid oil supplementation on visceral fat was investigated., Methods: Male Sprague-Dawley rats were divided into 4 groups: control, exercise (Ex), control with licorice flavonoid oil supplementation (LFO), and exercise with licorice flavonoid oil supplementation (ExLFO) groups. The rats in the Ex and ExLFO groups ran on a treadmill (20-degree incline at 20 m/min for 30 min/day) 5 times a week for 7 weeks, and those in the LFO and ExLFO groups were orally administered with licorice flavonoid oil daily using a feeding needle., Results: Exercise or licorice flavonoid oil supplementation resulted in the reduction of the visceral fat mass and adipocyte size, respectively. In addition, exercise combined with licorice flavonoid oil supplementation more effectively decreased both measures. Exercise alone increased the β-hydroxyacyl-CoA dehydrogenase (β-HAD) and citrate synthase (CS) activities in the soleus and plantaris muscles, and licorice flavonoid oil supplementation alone increased the hepatic carnitine palmitoyl transferase-2 (CPT-2) activity. Furthermore, the combination of exercise and licorice flavonoid oil supplementation enhanced the both muscular β-HAD and CS activities, and hepatic CPT-2 activity., Conclusions: These results suggest that exercise combined with licorice flavonoid oil supplementation may be effective to decrease visceral adipose tissue via enhancing skeletomuscular and hepatic fatty acids oxidative capacity.

A critical factor for preventing osteoporosis after menopause is attenuation of the accelerated turnover rate of bone metabolism. The present randomized controlled study was conducted to clarify the effects of a lemon beverage with calcium (Ca) supplementation that makes use of the chelating action of citric acid. Comprehensive evaluations of bone were performed by assessments of bone mineral density (BMD) and biomarkers related to bone turnover. Seventy-nine postmenopausal women were enrolled and asked to participate in an 11-month continuous intake of the test beverages. The subjects were divided into three groups: those who consumed a lemon beverage containing citric acid with Ca supplementation (LECA group), those who consumed a lemon beverage containing citric acid without Ca supplementation (LE group), and those who consumed no test beverage (control group). Using a double-blind protocol, subjects in the LECA and LE groups consumed one bottle containing 290 mL of the test beverage each day. The ratio of change in BMD after 11 months was significantly higher in the LECA group as compared to the control and LE groups. The LECA group also showed significant decreases in concentrations of tartrate-resistant acid phosphatase 5b (TRACP-5b), a bone resorption marker, and bone alkaline phosphatase (BAP) as compared to the other groups, as well as a significant decrease in concentration of osteocalcin (OC), a bone formation marker, as compared to the LE group. Based on our findings, we speculated that bone resorption and bone formation in postmenopausal women might be suppressed along with an increase in Ca resorption caused by chelation of citric acid in association with continuous ingestion of a Ca-supplemented lemon beverage containing citric acid, resulting in suppression of high bone metabolic turnover. In addition, the results provide information regarding BMD maintenance in the bones of the trunk, including the lumbar spine and proximal femur., Competing Interests: M. H. and T. I are the employees of Sapporo Holdings Ltd., the funder of this study. The other authors declare no conflicts of interest., (Copyright © 2021 Hiromi Ikeda et al.)

We examined the effects of mild hyperbaric oxygen (mHBO) exposure on capillary rarefaction in skeletal muscles of rats with diabetes. Streptozotocin (100 mg/kg) was administered to male Wistar rats via the tail vein to prepare a diabetic model. These rats were divided into 2 groups: the group with mHBO exposure (1.25 atmospheres absolute (ATA) with 36% oxygen; 3 h/day) and the group without mHBO exposure. Age-matched rats were used as the control group. Eight weeks later, the soleus of the rats was removed and then analyzed. With the onset of diabetes mellitus, capillary number, diameter, and volume in the soleus of the rats with diabetes decreased compared with those of the rats in the control group. In addition, increased anti-angiogenic thrombospondin-1 (TSP-1) and decreased pro-angiogenic murine double minute 2 (MDM-2) protein expressions were observed in the rats with diabetes. Alternatively, mHBO exposure attenuated the decrease in capillary diameter and volume in skeletal muscles of rats with diabetes, suppressed the overexpression of TSP-1, and restored the MDM-2 expression. These results indicate the exposure of mHBO partially attenuates capillary rarefaction in diabetic soleus muscle.

The purpose of the study was to investigate the effects of ambulatory reloading following hindlimb unloading on the three-dimensional (3D) capillary architecture of rat soleus muscle. In this study, 15 male Sprague-Dawley rats were used. The rats were randomly assigned to the following 3 groups: a normal weight bearing control group (CON), 14 days of hindlimb unloading group (HU), and 14 days of hindlimb unloading followed by 7 days of ambulatory reloading group (HU-RL). The capillary diameter and volume were measured using confocal laser microscopy, and capillary number was determined by two-dimensional (2D) capillary staining in the soleus muscle of each group. The capillary diameter and volume as well as the capillary number were significantly lower in the HU group than in the CON group and significantly higher in the HU-RL group than in the HU group. These results provided novel information about the effectiveness of reloading following unloading on not only the 2D increase in capillary number but also the 3D capillary remodeling in the diameter and volume within the unloaded soleus muscle., (Copyright © 2020. Published by Elsevier GmbH.)

The effects of a combination of the antioxidant astaxanthin (AX) and electrical stimulation (ES) on muscle mass and mitochondrial oxidative capacity were investigated in the soleus muscle of hindlimb unloaded rats. Five groups of male Sprague-Dawley rats were used; control, 1-week hindlimb unloading (HU), HU + AX, HU + ES, and HU + AX + ES. Respective rats in the AX groups received 50-mg/kg AX twice daily during HU. Calf muscles of rats in the ES groups were electrically stimulated for 240 s/day during HU. One-week HU decreased muscle mass along with decreased FoxO3a phosphorylation and increased ubiquitinated proteins expressions, decreased oxidative enzymatic activity accompanied with decline in PGC-1α protein expression, and increased reactive oxygen species production. However, the combination treatment could synergistically attenuate/suppress all HU-related changes, suggesting protective effects on muscle atrophy and decreased muscle oxidative capacity due to chronic neuromuscular inactivity.

A monogalactosyl diacylglyceride (MGDG) was isolated as an antiviral component from Coccomyxa sp. KJ (IPOD FERM BP-22254) via bioassay-guided fractionation. α-Linolenic acid (C18:3) and 7,10,13-hexadecatrienoic acid (C16:3) accounted for approximately 72% and 23%, respectively, of the MGDG total fatty acids of the MGDG. The MGDG showed virucidal activity against herpes simplex virus type 2 (HSV-2), a pathogen that causes genital herpes. Physical changes in HSV-2 shape were observed after treatment with MGDG, including a decrease in particle size, and possible damage to the viral envelope, as assessed using electron microscopy. In accordance with the morphological findings, virus particles lost their ability to bind to host cells. HSV-2 treated with high concentrations of MGDG resulted in no pathogenicity in an animal model, indicating that MGDG exhibits irreversible virucidal activity against HSV-2 particles. In the animal model of HSV-2-induced genital herpes, intravaginally administered MGDG exerted a prophylactic effect by suppressing viral yields in the genital cavity and formation of herpetic lesions, resulting in a higher survival rate in treated mice than control mice administered solvent. Thus, MGDG offers a novel prophylactic option against HSV infections., Competing Interests: KA and MK are employed by DENSO CORPORATION. We have applied for patent in Japan, #2018-143049 (Virucidal agents). This does not alter our adherence to PLOS ONE policies on sharing data and materials.

The protective effects of Brazilian propolis on capillary regression induced by chronically neuromuscular inactivity were investigated in rat soleus muscle. Four groups of male Wistar rat were used in this study; control (CON), control plus Brazilian propolis supplementation (CON + PP), 2-week hindlimb unloading (HU), and 2-week hindlimb unloading plus Brazilian propolis supplementation (HU + PP). The rats in the CON + PP and HU + PP groups received two oral doses of 500 mg/kg Brazilian propolis daily (total daily dose 1000 mg/kg) for 2 weeks. Unloading resulted in a decrease in capillary number, luminal diameter, and capillary volume, and an increase in the expression of anti-angiogenic factors, such as p53 and TSP-1, within the soleus muscle. Brazilian propolis supplementation, however, prevented these changes in capillary structure due to unloading through the stimulation of pro-angiogenic factors and suppression of anti-angiogenic factors. These results suggest that Brazilian propolis is a potential non-drug therapeutic agent against capillary regression induced by chronic unloading.

Platelet-rich plasma (PRP) contains numerous growth factors and promotes bone fracture healing. The aim of this study was to evaluate the effectiveness of the controlled release of PRP from biodegradable gelatin hydrogel for promoting healing in a rabbit ischemic sternal model. PRP was prepared from the whole blood of a Japanese white rabbit. Sixteen rabbits were randomized into four groups (each n = 4) and all underwent median sternotomy and bilateral internal thoracic artery removal. Before the sternum was closed, the following solutions were applied between the sternum incisions in three of the groups: 30 mg of gelatin hydrogel incorporating 300 μL of phosphate-buffered saline, 300 μL of a solution form of PRP, or 30 mg of gelatin hydrogel incorporating 300 μL of PRP (PRP + Gel). The fourth group acted as a control. Sternal healing was evaluated by histology and microcomputed tomography 7 days after the intervention. The PRP + Gel group showed a significantly higher proportion of fibrosis within the fracture area (an indicator of sternal healing) than the other groups and a significantly higher mean intensity of osteocalcin. These results indicate that the controlled release of PRP from locally applied gelatin hydrogel was markedly effective in enhancing sternal healing in the early postoperative period. This novel therapy could potentially help prevent complications, such as deep sternal wound infection and could result in early postoperative ambulation after median sternotomy.

Immobilization induces skeletal muscle fibrosis characterized by increasing collagen synthesis in the perimysium and endomysium. Transforming growth factor-β1 (TGF-β1) is associated with this lesion via promoting differentiation of fibroblasts into myofibroblasts. In addition, reactive oxygen species (ROS) are shown to mediate TGF-β1-induced fibrosis in tissues. These reports suggest the importance of ROS reduction for attenuating skeletal muscle fibrosis. Astaxanthin, a powerful antioxidant, has been shown to reduce ROS production in disused muscle. Therefore, we investigated the effects of astaxanthin supplementation on muscle fibrosis under immobilization. In the present study, immobilization increased the collagen fiber area, the expression levels of TGF-β1, α-smooth muscle actin, and superoxide dismutase-1 protein and ROS production. However, these changes induced by immobilization were attenuated by astaxanthin supplementation. These results indicate the effectiveness of astaxanthin supplementation on skeletal muscle fibrosis induced by ankle joint immobilization.

We investigated the prevalences and risk factors for peri-implant diseases in Japanese adult dental patients attending a follow-up visit at dental hospitals or clinics as part of their maintenance program. This cross-sectional multicenter study enrolled patients with dental implants who attended regular check-ups as part of a periodontal maintenance program during the period from October 2012 through September 2013. Patients with implants with at least 3 years of loading time were included in the study. The condition of peri-implant tissue was examined and classified into the following categories: healthy, peri-implant mucositis, and peri-implantitis. Patients were also evaluated for implant risk factors. A total of 267 patients (110 men, 157 women; mean age: 62.5 ± 10.7 years) were analyzed. The prevalence of patient-based peri-implant mucositis was 33.3% (n = 89), and the prevalence of peri-implantitis was 9.7% (n = 26). Poor oral hygiene and a history of periodontitis were strong risk factors for peri-implant disease. The present prevalences were lower than those previously reported. The quality of periodontal therapy before and after implant installation and patient compliance and motivation, as indicated by plaque control level, appear to be important in maintaining peri-implant tissue health.

Reduced ovarian hormone levels associated with menopause or ovariectomy (OVX) not only result in vascular dysfunction but also lead to structural abnormalities in capillaries. Therefore, the effect of OVX on the three-dimensional (3-D) architecture of capillary networks and the underlying molecular mechanisms were investigated in rat soleus muscle. Seven-week-old female Wistar rats were divided into the OVX and sham-treated (Sham) groups. The OVX group exhibited lower endurance exercise capacity compared to the sham group and resulted in decreased capillary diameter, number of anastomoses and capillary/anastomosis volume in soleus muscle, indicating 3-D structural abnormalities of capillary networks. Furthermore, OVX led to increased concentrations of thrombospondin-1 (TSP-1) protein and a decreased VEGF-A/TSP-1 ratio, an indicator of angio-adaptations, in soleus muscle compared with the Sham group. These results indicate OVX may induce 3-D capillary regression in soleus muscle through an imbalance between VEGF-A and TSP-1 expression, possibly associated with decreased exercise tolerance in ovariectomized rats., (Copyright © 2015 Elsevier GmbH. All rights reserved.)

Introduction: We determined the effects of low-intensity exercise on the three-dimensional capillary structure and associated angiogenic factors in the soleus muscle of Goto-Kakizaki (GK) diabetic rats., Methods: Four groups of male rats were studied: sedentary nondiabetic (Con), exercised nondiabetic control (Ex), sedentary GK, and exercised GK (GK+Ex). Rats in the Ex and GK+Ex groups were subjected to chronic low-intensity running on a treadmill (15 m/min, 60 min/session, 5 sessions/week for 3 weeks)., Results: Although mean capillary volume and diameter were lower in the GK compared with all other groups, low-intensity exercise increased both of these measures in GK rats. Mitochondrial markers, i.e., SDH activity and PGC-1α expression, and the levels of angiogenic factors were higher in the GK+Ex than all other groups. Exercise increased vascular endothelial growth factor (VEGF) protein levels and the VEGF-to-TSP-1 ratio, an indicator of angiogenesis, in GK rats., Conclusions: Combined, the results indicate that low-intensity exercise reduces some of the microcirculatory complications in type 2 diabetic muscles., (© 2014 Wiley Periodicals, Inc.)

A chronic decrease in neuromuscular activity (activation and/or loading) results in muscle atrophy and capillary regression that are due, in part, to the overproduction of reactive oxygen species. We have reported that antioxidant treatment with astaxanthin attenuates the overexpression of reactive oxygen species in atrophied muscles that, in turn, ameliorates capillary regression in hindlimb-unloaded rats. Astaxanthin supplementation, however, had little effect on muscle mass and fibre cross-sectional area. In contrast, intermittent loading of the hindlimbs of hindlimb-unloaded rats ameliorates muscle atrophy. Therefore, we hypothesized that the combination of astaxanthin supplementation and intermittent loading would attenuate both muscle atrophy and capillary regression during hindlimb unloading. As expected, 2 weeks of hindlimb unloading resulted in atrophy, a decrease in capillary volume and a shift towards smaller-diameter capillaries in the soleus muscle. Intermittent loading alone (1 h of cage ambulation per day) attenuated atrophy of the soleus, while astaxanthin treatment alone maintained the capillary network to near control levels. The combination of intermittent loading and astaxanthin treatment, however, ameliorated atrophy of the soleus and maintained the capillary volume and luminal diameters and the superoxide dismutase-1 protein levels near control values. These results indicate that intermittent loading combined with astaxanthin supplementation could be an effective therapy for both the muscle atrophy and the capillary regression associated with a chronic decrease in neuromuscular activity., (© 2014 The Authors. Experimental Physiology © 2014 The Physiological Society.)

The periodontal ligament (PDL) is one of the connective tissues located between the tooth and bone. It is characterized by rapid turnover. Periodontal ligament fibroblasts (PDLFs) play major roles in the rapid turnover of the PDL. Microarray analysis of human PDLFs (HPDLFs) and human dermal fibroblasts (HDFs) demonstrated markedly high expression of chemokine (CXC motif) ligand 12 (CXCL12) in the HPDLFs. CXCL12 plays an important role in the migration of mesenchymal stem cells (MSCs). The function of CXCL12 in the periodontal ligament was investigated in HPDLFs. Expression of CXCL12 in HPDLFs and HDFs was examined by RT-PCR, qRT-PCR and ELISA. Chemotactic ability of CXCL12 was evaluated in both PDLFs and HDFs by migration assay of MSCs. CXCL12 was also immunohistochemically examined in the PDL in vivo. Expression of CXCL12 in the HPDLFs was much higher than that in HDFs in vitro. Migration assay demonstrated that the number of migrated MSCs by HPDLFs was significantly higher than that by HDFs. In addition, the migrated MSCs also expressed CXCL12 and several genes that are familiar to fibroblasts. CXCL12 was immunohistochemically localized in the fibroblasts in the PDL of rat molars. The results suggest that PDLFs synthesize and secrete CXCL12 protein and that CXCL12 induces migration of MSCs in the PDL in order to maintain rapid turnover of the PDL.

Botryococcus braunii is a green, colonial microalga that produces large amounts of hydrocarbons. B. braunii B70 was estimated to be B race by the incorporation of radioactivity from l-[methyl(14)C]-methionine into hydrocarbon. The hydrocarbon-synthesizing activity of B70 cells was determined by feeding experiments using (14)C-compounds. NaH(14)CO(3) incorporation rate into the hydrocarbon was high in the early logarithmic growth phase but it declined thereafter. Hydrocarbon-synthesizing activity from [2-(14)C] pyruvate in 15-day cells was 80% of that in 5-day cells. In contrast, hydrocarbon-synthesizing activity from NaH(14)CO(3) and l-[methyl(14)C]-methionine decreased remarkably by 15 days after inoculation. Hence, the allocation of carbon was a regulatory step in hydrocarbon biosynthesis during the early logarithmic growth phase. The high activity of pentose phosphate pathway in the early logarithmic growth was seemed to be the contribution of the supply of NADPH for botryococcene synthesis., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: Azithromycin is an azalide antibiotic, effective against a wide range of oral bacteria including periodontopathic bacteria. Azithromycin is taken up by phagocytes and is released into inflamed tissue over time. The concentration of azithromycin in inflamed periodontal tissues over time has not been studied. In this study, we determined the azithromycin concentration in the gingiva and inflammatory connective tissue of the periodontal pocket in periodontal patients who had been administered azithromycin systemically. We also evaluated the clinical and microbiologic effects of azithromycin., Methods: Thirty-four patients with periodontitis were prescribed azithromycin 500 mg once daily for 3 days. During the 14-day study, clinical parameters (probing depth, gingival index, bleeding on probing, and gingival crevicular fluid level) were recorded, subgingival plaque was collected for bacteriologic examination, and the azithromycin concentration in the tissues lining the periodontal pocket was measured by agar diffusion bioassay., Results: Clinical parameters significantly improved after administration of azithromycin. The total number of cultivated bacteria also significantly decreased by day 4 but slightly increased after day 7. Sustained reduction in levels of six periodontopathic bacteria was not apparent until day 14. On day 7, the azithromycin concentration in the tissues lining the periodontal pockets was 50% of that on day 4, and on day 14 only 20%., Conclusion: Azithromycin is detectable in inflamed periodontal tissues >or=14 days after systemic administration; it is associated with clinical and microbiologic improvement.

Background: One-stage full-mouth disinfection (FMD), in which full-mouth scaling and root planing (SRP) is performed with adjunctive use of chlorhexidine, was introduced in 1995. There have been several reports on the effectiveness of this treatment protocol. However, FMD was reported to induce pyrexia frequently. We examined the effects of full-mouth SRP in conjunction with azithromycin administered orally before SRP to control the number of bacteria. The purpose of this study was to compare the effects of full-mouth SRP using azithromycin with conventional SRP., Methods: Thirty-four subjects (17 in the test group and 17 in the control group) with severe chronic periodontitis were selected. The subjects of the test group had azithromycin 3 days before full-mouth SRP. Clinical parameters (probing depth [PD], gingival index [GI], bleeding on probing [BOP], and gingival crevicular fluid [GCF]), total number of bacteria, and number of black pigment-producing rods (BPRs) were evaluated at baseline and 5, 13, and 25 weeks after baseline., Results: All clinical parameters improved in the test group more than in the control group. In the bacteriologic examination, the total number of bacteria did not change during the examination. In the test group, BPRs were not detected until 13 weeks. However, BPRs were detected in the control group by 13 weeks., Conclusion: It was shown that full-mouth SRP using systemically administered azithromycin was a clinically and bacteriologically useful basic periodontal treatment for severe chronic periodontitis.

The purpose of this study was to identify the periodontal regeneration factors of enamel protein extracts that induce cementum and bone regeneration in vivo. Cementum regeneration, one aspect of periodontal ligament regeneration, was examined using a buccal dehiscence model of dogs. Enamel matrix protein fractions were prepared from developing porcine incisors. Cementum-regeneration activity was found to reside in a protein aggregate composed of amelogenins and sheath proteins extracted from newly formed secretory enamel. Cementum-regeneration activity was not observed in protein fractions containing only amelogenin or its derivatives. The sheath proteins were purified to homogeneity and tested for alkaline phosphatase (ALP)-inducing activity on human periodontal ligament (HPDL) cells. The induction of ALP was observed following application of the 17-kDa sheath protein but not of the lower-molecular-weight sheath proteins. Although transforming growth factor-beta1 also shows ALP-inducing activity, contamination with growth factors was excluded because synthetic peptides (based on the sheath protein's sequence) also showed ALP-inducing activity. The 17-kDa sheath protein showed both cytodifferentiation and cementum-regeneration activity, but it is unclear whether its cementum-regeneration activity is derived from its ALP-inducing activity on HPDL cells.

This study describes the generation of an active hematopoietic marrow within the confines of a biodegradable, macroporous polyester scaffold, seeded with rat osteogenic cells, after subcutaneous implantation in nude mice. A macroporous, poly(DL-lactide-co-glycolide) polymer scaffold, into which resorbable calcium phosphate particles were incorporated, was seeded with rat bone marrow-derived cells. Scanning electron microscopy of the cell-seeded scaffold demonstrated confluent cell colonization. Scaffolds seeded with cells were implanted under the dorsum of immunocompromised mice for 5 weeks. Histological analysis revealed bone formation along the scaffold pores creating bony cavities within which a host-derived, hematopoietic marrow was observed which included hematopoietic precursors, megakaryocytes, fat cells, and numerous marrow sinusoids. In those areas where bone was not elaborated on the scaffold surface, no marrow genesis was observed and the scaffold interstices were filled with fibrous tissue. These results demonstrate the utility of this biodegradable scaffold in delivery of a phenotypically functional cell population for bone tissue and bone marrow engineering applications. Moreover, the recapitulation of hematopoietic marrow tissue within the engineered bony cavities also provides a new experimental environment with which to further investigate the interactions of hematopoietic and nonhematopoietic compartments of the marrow microenvironment.

Periodontitis is a common inflammatory disease causing destruction of periodontal tissues. It is a multifactor disease involving genetic factors and oral environmental factors. To determine genetic risk factors associated with aggressive periodontitis or severe chronic periodontitis, single nucleotide polymorphisms (SNPs) in multiple candidate genes were investigated in Japanese. We studied 134 patients with aggressive periodontitis, 117 patients with severe chronic periodontitis, and 125 healthy volunteers without periodontitis, under case-control setting, and 310 SNPs in 125 candidate genes were genotyped. Association evaluation by Fisher's exact test (p < 0.01) revealed statistically significant SNPs in multiple genes, not only in inflammatory mediators (IL6ST and PTGDS, associated with aggressive periodontitis; and CTSD, associated with severe chronic periodontitis), but also in structural factors of periodontal tissues (COL4A1, COL1A1, and KRT23, associated with aggressive periodontitis; and HSPG2, COL17A1, and EGF, associated with severe chronic periodontitis). These appear to be good candidates as genetic factors for future study.

Three groups of male Wistar rats received daily subcutaneous injections of 10 mg/kg of hydrocortisone (HC group), 300 mg/kg of beta-aminopropionitrile (BAPN group), or saline (control group), for 10 days. The shear stress-strain and stress-relaxation properties of the incisor periodontal ligament were examined in transverse sections from dissected mandibles. Both the maximum shear stress and failure strain energy density increased significantly following the administration of hydrocortisone. The maximum shear stress decreased following the administration of BAPN. However, the stress-relaxations in the initial 10 min did not show significant differences among the three groups. Polarized light microscopic analysis revealed that the retardation value of the collagen fibers was highest in the HC group and lowest in the BAPN group for the bone-related area, but not for the tooth-related and middle areas of the ligament. It is suggested that the changes induced by hydrocortisone or BAPN occurred mainly in the elastic components and to a minor extent in the viscous components although the physical and biomechanical properties are determined by the interaction of all the various components. We also suggest that the main response to the drugs occurred in the collagen fibers in the bone-related area of the ligament.