Comprehensive lifestyle modification interventions for metabolic syndrome: A systematic review and meta-analysis.

INTRODUCTION: Previous systematic reviews and meta-analyses have mainly focused on improvements in the number of metabolic syndrome risk factors and individual changes in each risk factor, making it challenging to examine the impact of comprehensive lifestyle modification interventions on adherence to recommended health behaviors. To address this gap, we conducted a systematic and meta-analysis aimed at identifying clinical parameter levels associated with lifestyle modification outcomes and adherence to recommended health behaviors for individuals with metabolic syndrome. METHODS: A total of seven studies retrieved from four databases (CINAHL, Medline via PubMed, American Psychological Association PsycINFO, and Embase) were included in the review. The selected studies, which demonstrated improvements in health behaviors, all included diet and exercise as main factors of comprehensive lifestyle modification in home settings. RESULTS: Our findings suggest that a 6-month comprehensive intervention including diet and exercise can be effective in decreasing glucose levels and systolic blood pressure. However, given the limited available data, further studies investigating the efficacy of interventions of varying durations are needed. DISCUSSION: Although our review included a small number of studies, comprehensive lifestyle modifications consisting of at least two components (primarily diet and exercise) can improve health behaviors and some clinical parameters among individuals with metabolic syndrome. Future studies are needed to investigate the long-term effects of lifestyle modifications on health behavior adherence and explore effective interventions to address certain clinical parameters, such as high-density lipoprotein levels. Also, we recommend using objective and quantifiable measure to compare adherence to recommended lifestyle modifications across studies. CLINICAL RELEVANCE: This research provides empirical evidence of the effectiveness of comprehensive lifestyle modification and emphasizes the need to develop long-term nursing strategies in public health that can be used to effectively manage metabolic syndrome.

Salivary Cortisol and Melatonin, Sleep, and Behavioral Patterns in Older Adults Living With Dementia.

BACKGROUND: Over half of the older adults living with dementia have behavioral and psychological symptoms of dementia (BPSD), including sleep disturbance; however, little is known about physiological markers. Salivary cortisol and melatonin have been identified as potential biomarkers of BPSD, with evidence suggesting a relationship between these biomarkers and various behavioral factors, as well as sleep and activity patterns. OBJECTIVES: The aim of this study was to investigate the time-dependent changes in salivary cortisol and melatonin levels in older adults with dementia, their relationship with the sleep-wake cycle, and their correlation with BPSD symptoms and behavioral factors. METHODS: This observational study conducted in Seoul and Gyeonggi-do, South Korea, used data from 172 older adults with dementia, measuring sleep and activity patterns for 2 weeks using a wearable device, in addition to administering questionnaires for neuropsychiatric and psychological symptoms-the Neuropsychiatric Inventory, Cohen-Mansfield Agitation Inventory, and Cornell Scale for Depression in Dementia. Salivary cortisol and melatonin levels were measured at four time points and divided into four groups based on a dual-trajectory model. Differences among the groups were analyzed using one-way analysis of variance. RESULTS: The participants showed normal but heterogeneous patterns of salivary cortisol and melatonin levels. Dual-trajectory pattern analysis showed that higher levels of melatonin during the daytime were correlated with poor nighttime sleep efficiency and decreased disinhibited behaviors, and higher levels of cortisol at all four time points were associated with decreased physical activity. DISCUSSION: Measuring and analyzing periodic changes in cortisol and melatonin levels can predict various behavioral symptoms (e.g., sleep disturbances, activity counts, and disinhibition) in older adults with dementia. A study with an experimental design is needed to discover the direct physiological interactions between cortisol, melatonin, and these symptoms.

Plasma Myokine Profiles in Patients With AChR- and MuSK-Ab-Positive Myasthenia Gravis.

BACKGROUND AND PURPOSE: Myokines include cytokines secreted by muscle fibers, which are the final targets of myasthenia gravis (MG). This pilot study investigated whether myokine plasma concentrations are altered in patients with MG and assessed the association between the concentration of each myokine and disease severity. METHODS: We compared the plasma concentrations of 15 myokines in 63 patients with acetylcholine receptor antibody (Ab)-positive MG and 14 with muscle-specific tyrosine kinase Ab-positive MG (MuSK MG) with those in 15 healthy controls. Plasma myokine concentrations were measured using a Luminex multiplex assay kit with magnetic beads that contained Abs for 15 myokines. Correlations between myokine concentration and clinical scale results were analyzed. RESULTS: The concentration of fractalkine in plasma was higher in MG (median [interquartile range]=419.6 [38.7-732.5] pg/mL) than in controls (158.5 [0.0-313.2] pg/mL, p=0.034). The leukemia inhibitory factor concentration was also found to be higher in MuSK MG (29.9 [8.7-40.1] pg/mL) than in healthy controls (7.6 [0.0-15.6] pg/mL, p=0.013). Fatty-acid-binding protein 3 (FABP3) concentrations in plasma were positively associated with clinical parameters for MG severity, including scores on the Quantitative Myasthenia Gravis score (p=0.008), Myasthenia Gravis Activities of Daily Living (p=0.003), and Myasthenia Gravis Composite (p=0.024) scales. FABP3 concentration in plasma tended to decrease after treatment in patients without additional relapse but increased in those with further relapse. CONCLUSIONS: The plasma myokine profile was significantly altered in patients with MG. FABP3 concentration may be useful in assessing disease severity and predicting the treatment response.

The effectiveness of non-pharmacological interventions using information and communication technologies for behavioral and psychological symptoms of dementia: A systematic review and meta-analysis.

BACKGROUND: Although behavioral and psychological symptoms of dementia are a global public health challenge, non-pharmacological interventions using information and communication technologies can be an affordable, cost-effective, and innovative solution. OBJECTIVES: This study aimed to examine the effectiveness of non-pharmacological interventions using information and communication technologies on the behavioral and psychological symptoms of dementia and identify potential moderators of intervention effects. DESIGN: Systematic review and meta-analysis of randomized controlled trials. METHODS: A systematic literature review was conducted using PubMed, CINAHL, PsycINFO, Embase, and the Cochrane Library from May 2022. Randomized controlled trials that examined the effects of non-pharmacological interventions using information and communication technologies on the behavioral and psychological symptoms of dementia were included. A meta-analysis using a random-effects model was performed to calculate the pooled standardized mean differences between overall symptoms and each type of symptom. For moderator analyses, subgroup and meta-regression analyses were performed. RESULTS: Sixteen trials (15 articles) met the eligibility criteria. The interventions were grouped into activity engagement interventions using digital health that provided music and reminiscence therapy, physical exercise, social interaction interventions using social robots, and telehealth-based care aid interventions that provided coaching or counseling programs. Pooled evidence demonstrated that non-pharmacological interventions using information and communication technologies exerted a large effect on depression (SMD = -1.088, 95% CI -1.983 to -0.193, p = 0.017), a moderate effect on overall behavioral and psychological symptoms of dementia (SMD = -0.664, 95% CI -0.990 to -0.338, p < 0.001), and agitation (SMD = -0.586, 95% CI -1.130 to -0.042, p = 0.035). No effects on neuropsychiatric symptoms (SMD = -0.251, 95% CI -0.579 to 0.077, p = 0.133), anxiety (SMD = -0.541, 95% CI -1.270 to 0.188, p = 0.146), and apathy (SMD = -0.830, 95% CI -1.835 to 0.176, p = 0.106) were reported. Moderator analyses identified the mean age of the participants as a potential moderator of intervention effects. CONCLUSIONS: Evidence from this systematic review and meta-analysis suggests that non-pharmacological interventions, using information and communication technologies, were an applicable approach to managing behavioral and psychological symptoms among older adults with dementia, with moderate to large effect sizes. However, evidence on anxiety and apathy is inconclusive due to the limited number of existing randomized controlled trials. Future studies with subgroup analyses are warranted to conclude the most effective types of intervention using information and communication technologies for each type of symptom. REGISTRATION: CRD42021258498.

Feasibility and efficacy of TouchCare system using application for older adults living alone: a pilot pre-experimental study.

BACKGROUND: With the number of older people living alone continuously rising, health-monitoring systems using information and communication technology (ICT) have been developed to manage their health issues. Life logging and human body communication sensor, types of ICT, have been adapted to manage and monitor health status of the elderly. However, its feasibility and efficacy remain unclear. This study aimed to examine the feasibility of TouchCare system which combined life logging with human body communication technology and its effect on the physical and psychological status of older adults living alone. METHODS: The TouchCare system, which consisted of a wearable watch, touchpad sensors, TouchCare application, and context-aware artificial intelligence, was developed by DNX Co. Ltd and used by the participants for 5 months. Out of the 111 selected participants, 91 replied to the satisfaction survey, and 22 participated in further investigation regarding their physical and psychological status. Finally, health assessment from 14 participants and sensor data from 13 participants (mean age = 77.4; SD = 3.8) were analyzed to compare their health status and health-related behaviors before and after use of the system. RESULTS: Out of the 91 participants who took the survey, 51.6% were satisfied with the system. Nutritional status (pre-intervention (10.6 ± 2.0) vs. post-intervention (11.8 ± 1.9), P = 0.04) and fall efficacy (pre-intervention (89.2 ± 15.3) vs. post-intervention (99.9 ± 0.5), P = 0.001) significantly improved after use of the system. Chronic pain (pre-intervention (4.8 ± 2.5) vs. post-intervention (4.4 ± 3.7), P = 0.78) and depressive symptoms (pre-intervention (5.7 ± 3.9) vs. post-intervention (5.4 ± 3.1), P = 0.60) reduced, while cognitive function (pre-intervention (4.1 ± 1.4) vs. post-intervention (4.6 ± 1.1), P = 0.15) and physical performance related to walking improved (pre-intervention (3.9 ± 0.2) vs. post-intervention (4.0 ± 0), P = 0.35), but were not significant. Behaviors related to physical activity and gait improved after use of the system; touch counts of refrigerator and microwave also increased with a decrease in night touch counts. CONCLUSIONS: The TouchCare system was acceptable to older people living alone, and it efficiently managed their daily living while promoting their health-related behaviors. Further experimental studies are required to verify the effectiveness of the system, and to develop the system which meet the individualized needs of older people living alone.

Coupled mechanical creep and bio-compression and residual settlement in a multi-stage municipal solid waste landfill, Korea.

Based on a field monitored dataset measured at landfill #1 over 21 years, the characteristics of settlement coupling mechanical creep and biodegradation and the residual settlement were analyzed. Since landfill #1 is a multi-stage municipal solid waste (MSW) landfill where dykes are constructed after landfilling for subsequent waste fills, the waste decomposition between the lower and upper lifts was quite different and it is difficult to discern between the mechanical creep and bio-compression on the settlement curves. The compression ratio coupled with mechanical creep and bio-compression and the residual compression ratio were determined as 0.233 and 0.068, respectively. This implies that biodegradation was gradually and significantly reduced in the MSW settlement behavior after the residual settlement began. The starting date of residual settlement was distributed between 3821 and 5402 days from the initial date of landfilling. The settlement coupling mechanical creep and biodegradation (SMB) was 2.9 times larger than the residual settlement (SRS), and the duration of SMB is determined to be 0.3 times that of SRS. In addition, the remnant methane gas content existed in the landfill gas, and low-level biodegradation was still generated in the waste buried for more than 10 years after the residual settlement began.

Calculation of stresses on 3D scaffolds fabricated using extrusion-based bioprinting using a semi-analytical approach.

The scaffold is essential to tissue engineering. In particular, the mechanical property of scaffolds has a significant impact on the success rate of regeneration. While numerous techniques exist for measuring mechanical properties, Compression test, three-point bending test, and nano-indentation test are the most common. Nevertheless, the mechanical property of porous structures cannot be accurately measured by previous testing methods. Combining superposition principles with the Flamant solution, this study developed semi-analytical solutions. Through compression testing and FEM simulation, the semi-analytical solution was fully validated. The solution can calculate not only the maximum stress of layer-by-layer construction of complex 3D scaffolds, but also the maximum load-bearing capacity if the mechanical property of the material is known.

Gut microbe-derived metabolite trimethylamine N-oxide activates PERK to drive fibrogenic mesenchymal differentiation.

Intestinal dysbiosis is prominent in systemic sclerosis (SSc), but it remains unknown how it contributes to microvascular injury and fibrosis that are hallmarks of this disease. Trimethylamine (TMA) is generated by the gut microbiome and in the host converted by flavin-containing monooxygenase (FMO3) into trimethylamine N-oxide (TMAO), which has been implicated in chronic cardiovascular and metabolic diseases. Using cell culture systems and patient biopsies, we now show that TMAO reprograms skin fibroblasts, vascular endothelial cells, and adipocytic progenitor cells into myofibroblasts via the putative TMAO receptor protein R-like endoplasmic reticulum kinase (PERK). Remarkably, FMO3 was detected in skin fibroblasts and its expression stimulated by TGF-ß1. Moreover, FMO3 was elevated in SSc skin biopsies and in SSc fibroblasts. A meta-organismal pathway thus might in SSc link gut microbiome to vascular remodeling and fibrosis via stromal cell reprogramming, implicating the FMO3-TMAO-PERK axis in pathogenesis, and as a promising target for therapy.

Endrin potentiates early-stage adipogenesis in 3T3-L1 cells by activating the mammalian target of rapamycin.

Obesogens are a type of endocrine-disrupting chemicals (EDCs) that disrupt the human endocrine system, resulting in obesity and metabolic disease. Several obesogens, including bisphenol A, tolylfluanid, and some pesticides, have been identified and studied previously; however, the underlying molecular mechanisms by which obesogens interfere with adipogenesis and induce insulin resistance in adipocyte remain unknown. This study aims to determine which type of chemical is the most potent obesogen and to investigate its effect on adipogenesis-related gene expressions. 3T3-L1, a pre adipocyte cell line, was differentiated into mature adipocytes with either vehicle or various obesogens, including bisphenol A, tolylfluanid, and endrin, as well as corticosterone, at the same dose. Subsequently, intracellular and secreted triglyceride levels were measured, and the expression of genes and proteins involved in adipogenesis and lipogenesis was investigated. We found that endrin was the most potent regulator of adipogenic differentiation, as compared to tolylfluanid, bisphenol A, and corticosterone. Endrin increased intracellular and secreted triglyceride levels and enhanced the expression of adipogenic transcription factors as well as the terminal differentiation marker in a dose-dependent manner. During the early stages of differentiation, endrin enhanced mammalian target of rapamycin (mTOR) activity, which was suppressed by the pharmacological blockade of the protein kinase B-mTOR pathway, with repressed adipogenic differentiation. However, endrin did not change the expression levels of the downstream members of the mTOR signaling pathway or proteins related to lipolysis in response to insulin. Thus, we suggest that endrin potentiates early-stage adipogenic differentiation by activating the mTOR pathway.

Non-pharmacological interventions using information and communication technology for behavioral and psychological symptoms of dementia: A systematic review and meta-analysis protocol.

AIM: To review and examine the effectiveness of non-pharmacological interventions on behavioural and psychological symptoms of dementia using information and communication technology. DESIGN: This is a systematic review and meta-analysis. METHODS: The databases including PubMed, CINAHL with Full Text (EBSCOhost), PsycINFO, Embase, and the Cochrane Library will be searched for all published studies. Studies will be screened and selected with criteria described in PICOS format. Risk of bias will be assessed by the National Institute for Health and Clinical Excellence checklist. Data will be extracted from eligible studies and used to perform a meta-analysis examining the overall effects and effects on individual outcomes. Additionally, we will conduct meta-regression to examine the association between explanatory variables and behavioural and psychological symptoms. This study has been funded since June 2020. DISCUSSION: This study will be the first to reveal the effects of non-pharmacological interventions using information and communication technology on behavioural and psychological symptoms of dementia. Furthermore, this study will provide updated and valid evidence of interventions using this for managing behavioural and psychological symptoms of dementia. IMPACT: Although non-pharmacological interventions using information and communication technology for older adults living with dementia are continuously developing, their direct effect remains unclear. This study will evaluate the effectiveness of these interventions on behavioural and psychological symptoms of dementia and provide the evidence to implement these interventions among older adults living with dementia. Thus, caregivers and nursing staff can manage behavioural and psychological symptoms of dementia more effectively by incorporating information and communication technology.

SIRT3 Overexpression Ameliorates Asbestos-Induced Pulmonary Fibrosis, mt-DNA Damage, and Lung Fibrogenic Monocyte Recruitment.

Alveolar epithelial cell (AEC) mitochondrial (mt) DNA damage and fibrotic monocyte-derived alveolar macrophages (Mo-AMs) are implicated in the pathobiology of pulmonary fibrosis. We showed that sirtuin 3 (SIRT3), a mitochondrial protein regulating cell fate and aging, is deficient in the AECs of idiopathic pulmonary fibrosis (IPF) patients and that asbestos- and bleomycin-induced lung fibrosis is augmented in Sirt3 knockout (Sirt3-/-) mice associated with AEC mtDNA damage and intrinsic apoptosis. We determined whether whole body transgenic SIRT3 overexpression (Sirt3Tg) protects mice from asbestos-induced pulmonary fibrosis by mitigating lung mtDNA damage and Mo-AM recruitment. Crocidolite asbestos (100 µg/50 µL) or control was instilled intratracheally in C57Bl6 (Wild-Type) mice or Sirt3Tg mice, and at 21 d lung fibrosis (histology, fibrosis score, Sircol assay) and lung Mo-AMs (flow cytometry) were assessed. Compared to controls, Sirt3Tg mice were protected from asbestos-induced pulmonary fibrosis and had diminished lung mtDNA damage and Mo-AM recruitment. Further, pharmacologic SIRT3 inducers (i.e., resveratrol, viniferin, and honokiol) each diminish oxidant-induced AEC mtDNA damage in vitro and, in the case of honokiol, protection occurs in a SIRT3-dependent manner. We reason that SIRT3 preservation of AEC mtDNA is a novel therapeutic focus for managing patients with IPF and other types of pulmonary fibrosis.

Magneto mitochondrial dysfunction mediated cancer cell death using intracellular magnetic nano-transducers.

Mitochondria are crucial regulators of the intrinsic pathway of cancer cell death. The high sensitivity of cancer cells to mitochondrial dysfunction offers opportunities for emerging targets in cancer therapy. Herein, magnetic nano-transducers, which convert external magnetic fields into physical stress, are designed to induce mitochondrial dysfunction to remotely kill cancer cells. Spindle-shaped iron oxide nanoparticles were synthesized to maximize cellular internalization and magnetic transduction. The magneto-mechanical transduction of nano-transducers in mitochondria enhances cancer cell apoptosis by promoting a mitochondrial quality control mechanism, referred to as mitophagy. In the liver cancer animal model, nano-transducers are infused into the local liver tumor via the hepatic artery. After treatment with a magnetic field, in vivo mitophagy-mediated cancer cell death was also confirmed by mitophagy markers, mitochondrial DNA damage assay, and TUNEL staining of tissues. This study is expected to contribute to the development of nanoparticle-mediated mitochondria-targeting cancer therapy and biological tools, such as magneto-genetics.

The Sphingosine Kinase 1 Inhibitor, PF543, Mitigates Pulmonary Fibrosis by Reducing Lung Epithelial Cell mtDNA Damage and Recruitment of Fibrogenic Monocytes.

Idiopathic pulmonary fibrosis (IPF) is a chronic disease for which novel approaches are urgently required. We reported increased sphingosine kinase 1 (SPHK1) in IPF lungs and that SPHK1 inhibition using genetic and pharmacologic approaches reduces murine bleomycin-induced pulmonary fibrosis. We determined whether PF543, a specific SPHK1 inhibitor post bleomycin or asbestos challenge mitigates lung fibrosis by reducing mitochondrial (mt) DNA damage and pro-fibrotic monocyte recruitment-both are implicated in the pathobiology of pulmonary fibrosis. Bleomycin (1.5 U/kg), crocidolite asbestos (100 µg/50 µL) or controls was intratracheally instilled in Wild-Type (C57Bl6) mice. PF543 (1 mg/kg) or vehicle was intraperitoneally injected once every two days from day 7-21 following bleomycin and day 14-21 or day 30-60 following asbestos. PF543 reduced bleomycin- and asbestos-induced pulmonary fibrosis at both time points as well as lung expression of profibrotic markers, lung mtDNA damage, and fibrogenic monocyte recruitment. In contrast to human lung fibroblasts, asbestos augmented lung epithelial cell (MLE) mtDNA damage and PF543 was protective. Post-exposure PF543 mitigates pulmonary fibrosis in part by reducing lung epithelial cell mtDNA damage and monocyte recruitment. We reason that SPHK1 signaling may be an innovative therapeutic target for managing patients with IPF and other forms of lung fibrosis.

Dexras1 plays a pivotal role in maintaining the equilibrium between adipogenesis and osteogenesis.

BACKGROUND: Chronic steroid treatment causes an increase in visceral adiposity and osteoporosis. It is believed that steroids may alter a balance between differentiation of mesenchymal stem cells (MSCs) into either adipocytes or osteoblasts; however, the detailed molecular mechanisms are unclear. We previously identified Dexras1 as a critical factor that potentiates adipogenesis in response to glucocorticoids. Thus, in this study, we investigated the role of Dexras1 in maintaining the balance between chronic steroid treatment-associated adipogenesis and osteoporosis. MATERIAL AND METHODS: We treated wild type (WT) and Dexras1 knockout (KO) mice with dexamethasone for five weeks followed by 60% HFD for additional two weeks with dexamethasone. The changes of glucocorticoid-induced body weight gain and osteoporosis were analyzed. Bone marrow derived stromal cells (BMSCs) and mouse embryonic fibroblasts (MEFs) extracted from WT and Dexras1 KO mice, as well as MC3T3-E1 pre-osteoblasts and osteoclasts differentiated from RAW264.7 were analyzed to further define the role of Dexras1 in osteoblasts and osteoclasts. RESULTS: Dual-energy X-ray absorptiometry and micro-computed tomography analyses in murine femurs revealed that Dexras1 deficiency was associated with increased osteogenesis, concurrent with reduced adipogenesis. Furthermore, Dexras1 deficiency promoted osteogenesis of BMSCs and MEFs in vitro, suggesting that Dexras1 deficiency prevents steroid-induced osteoporosis. We also observed that Dexras1 downregulated SMAD signaling pathways, which reduced the osteogenic differentiation capacity of pre-osteoblast MC3T3-E1 cells into mature osteoblasts. CONCLUSION: We propose that Dexras1 is critical for maintaining the equilibrium between adipogenesis and osteogenesis upon steroid treatment.

Mitochondrial 8-oxoguanine DNA glycosylase mitigates alveolar epithelial cell PINK1 deficiency, mitochondrial DNA damage, apoptosis, and lung fibrosis.

Alveolar epithelial cell (AEC) apoptosis, arising from mitochondrial dysfunction and mitophagy defects, is important in mediating idiopathic pulmonary fibrosis (IPF). Our group established a role for the mitochondrial (mt) DNA base excision repair enzyme, 8-oxoguanine-DNA glycosylase 1 (mtOGG1), in preventing oxidant-induced AEC mtDNA damage and apoptosis and showed that OGG1-deficient mice have increased lung fibrosis. Herein, we determined whether mice overexpressing the mtOGG1 transgene (mtOgg1tg) are protected against lung fibrosis and whether AEC mtOGG1 preservation of mtDNA integrity mitigates phosphatase and tensin homolog-induced putative kinase 1 (PINK1) deficiency and apoptosis. Compared with wild type (WT), mtOgg1tg mice have diminished asbestos- and bleomycin-induced pulmonary fibrosis that was accompanied by reduced lung and AEC mtDNA damage and apoptosis. Asbestos and H2O2 promote the MLE-12 cell PINK1 deficiency, as assessed by reductions in the expression of PINK1 mRNA and mitochondrial protein expression. Compared with WT, Pink1-knockout (Pink1-KO) mice are more susceptible to asbestos-induced lung fibrosis and have increased lung and alveolar type II (AT2) cell mtDNA damage and apoptosis. AT2 cells from Pink1-KO mice and PINK1-silenced (siRNA) MLE-12 cells have increased mtDNA damage that is augmented by oxidative stress. Interestingly, mtOGG1 overexpression attenuates oxidant-induced MLE-12 cell mtDNA damage and apoptosis despite PINK1 silencing. mtDNA damage is increased in the lungs of patients with IPF as compared with controls. Collectively, these findings suggest that mtOGG1 maintenance of AEC mtDNA is crucial for preventing PINK1 deficiency that promotes apoptosis and lung fibrosis. Given the key role of AEC apoptosis in pulmonary fibrosis, strategies aimed at preserving AT2 cell mtDNA integrity may be an innovative target.

Serpina3c Regulates Adipogenesis by Modulating Insulin Growth Factor 1 and Integrin Signaling.

Preadipocyte differentiation can be induced upon a hormonal treatment, and various factors secreted by the cells may contribute to adipogenesis. In this study, RNA-seq revealed Serpina3c as a critical factor regulating the signaling network during adipogenesis. Serpina3c is a secretory protein and is highly expressed in fat tissues. Knockdown of Serpina3c decreased adipogenesis by attenuating the mitotic clonal expansion of 3T3-L1 cells. These cells exhibited decreases in integrin α5, which abolished the phosphorylation of integrin ß3. We found that Serpina3c inhibits a serine protease that regulates integrin α5 degradation. Knockdown of Serpina3c disrupted integrin-mediated insulin growth factor 1 (IGF-1) signaling and ERK activation. Serpina3c-mediated regulation of integrin-IGF-1 signaling is also associated with AKT activation, which affects the nuclear translocation of GSK3ß. Altogether, our results indicate that Serpina3c secreted from differentiating adipocytes inhibits serine proteases to modulate integrin/IGF-1-mediated ERK and AKT signaling and thus is a critical factor contributing to adipogenesis.

Transparent Body-Attachable Multifunctional Pressure, Thermal, and Proximity Sensor and Heater.

A multifunctional sensor capable of simultaneous sensing of temperature, pressure, and proximity has been developed. This transparent and body-attachable device is also capable of providing heat under low voltage. The multi-sensor consists of metal fibers fabricated by electrospinning and electroplating. The device comprises randomly deposited metal fibers, which not only provide heating but also perform as thermal and proximity sensors, and orderly aligned metal fibers that act as a pressure sensor. The sensor is fabricated by weaving straight rectangular electrodes on a transparent substrate (a matrix). The sensitivity is readily enhanced by installing numerous matrices that facilitate higher sensing resolution. The convective heat transfer coefficient of the heater is h = 0.014 W·cm-2·°C-1. The temperature coefficient of resistivity (TCR) and pressure sensitivity (ηP) are 0.038 °C-1 and 5.3 × 10-3 kPa-1, respectively. The superior sensitivity of the device is confirmed via quantitative comparison with similar devices. This multifunctional device also has a superior convective heat transfer coefficient than do other heaters reported in the literature.

Role of phospholipase D in bleomycin-induced mitochondrial reactive oxygen species generation, mitochondrial DNA damage, and pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a pernicious lung disease characterized by alveolar epithelial apoptosis, dysregulated repair of epithelial injury, scar formation, and respiratory failure. In this study, we identified phospholipase D (PLD)-generated phosphatidic acid (PA) signaling in the development of pulmonary fibrosis (PF). Of the PLD isoenzymes, the protein expression of PLD2, but not PLD1, was upregulated in lung tissues from IPF patients and bleomycin challenged mice. Both PLD1 (Pld1-/-)- and PLD2 (Pld2-/-)-deficient mice were protected against bleomycin-induced lung inflammation and fibrosis, thereby establishing the role of PLD in fibrogenesis. The role of PLD1 and PLD2 in bleomycin-induced lung epithelial injury was investigated by infecting bronchial airway epithelial cells (Beas2B) with catalytically inactive mutants of PLD (hPLD1-K898R or mPld2-K758R) or downregulation of expression of PLD1 or PLD2 with siRNA. Bleomycin stimulated mitochondrial (mt) superoxide production, mtDNA damage, and apoptosis in Beas2B cells, which was attenuated by the catalytically inactive mutants of PLD or PLD2 siRNA. These results show a role for PLD1 and PLD2 in bleomycin-induced generation of mt reactive oxygen species, mt DNA damage, and apoptosis of lung epithelial cells in mice. Thus, PLD may be a novel therapeutic target in ameliorating experimental PF in mice.

A Case of Huge Nasolabial Cyst in 56 Year-Old Patient

A nasolabial cyst is a rare, non-odontogenic cyst that develops within the area adjacent to the ala of the nose around the uppermost portion of the nasolabial crease. The origin of such a cyst is unclear but may be due to developmental problems. Clinical characteristic of asymptomatic nasolabial swelling and radiological findings are important for diagnosis. Treatment is usually surgical resection via a sublabial approach but can also involve incision and drainage or marsupialization. Unlike the typical clinical features reported in other cases, we experienced a case of a giant nasolabial cyst of 4.4 cm in a 56-year-old male with elevation of the nasal cavity base, gingival swelling, and perilesional bony destruction. In this case, we discussed the growth potential of a nasolabial cyst and proper timing of treatment.

Hypercapnia increases airway smooth muscle contractility via caspase-7-mediated miR-133a-RhoA signaling.

The elevation of carbon dioxide (CO2) in tissues and the bloodstream (hypercapnia) occurs in patients with severe lung diseases, including chronic obstructive pulmonary disease (COPD). Whereas hypercapnia has been recognized as a marker of COPD severity, a role for hypercapnia in disease pathogenesis remains unclear. We provide evidence that CO2 acts as a signaling molecule in mouse and human airway smooth muscle cells. High CO2 activated calcium-calpain signaling and consequent smooth muscle cell contraction in mouse airway smooth muscle cells. The signaling was mediated by caspase-7-induced down-regulation of the microRNA-133a (miR-133a) and consequent up-regulation of Ras homolog family member A and myosin light-chain phosphorylation. Exposure of wild-type, but not caspase-7-null, mice to hypercapnia increased airway contraction and resistance. Deletion of the Caspase-7 gene prevented hypercapnia-induced airway contractility, which was restored by lentiviral transfection of a miR-133a antagonist. In a cohort of patients with severe COPD, hypercapnic patients had higher airway resistance, which improved after correction of hypercapnia. Our data suggest a specific molecular mechanism by which the development of hypercapnia may drive COPD pathogenesis and progression.