Silver electroceutical technology to treat sarcopenia.

While the world is rapidly transforming into a superaging society, pharmaceutical approaches to treat sarcopenia have hitherto not been successful due to their insufficient efficacy and failure to specifically target skeletal muscle cells (skMCs). Although electrical stimulation (ES) is emerging as an alternative intervention, its efficacy toward treating sarcopenia remains unexplored. In this study, we demonstrate a silver electroceutical technology with the potential to treat sarcopenia. First, we developed a high-throughput ES screening platform that can simultaneously stimulate 15 independent conditions, while utilizing only a small number of human-derived primary aged/young skMCs (hAskMC/hYskMC). The in vitro screening showed that specific ES conditions induced hypertrophy and rejuvenation in hAskMCs, and the optimal ES frequency in hAskMCs was different from that in hYskMCs. When applied to aged mice in vivo, specific ES conditions improved the prevalence and thickness of Type IIA fibers, along with biomechanical attributes, toward a younger skMC phenotype. This study is expected to pave the way toward an electroceutical treatment for sarcopenia with minimal side effects and help realize personalized bioelectronic medicine.

The relationship between depressive mood and subjective health in centenarians and near-centenarians: a cross-sectional study from Korean centenarian cohort.

BACKGROUND: With the rapid increase in population longevity, more clinical attention is being paid to the overall health of long-lived people, especially centenarians. Subjective health, which is the perception of one's health status, predicts both mortality and declining physical function in older adults. The purpose of this study was to investigate the factors related to subjective health among centenarians and near-centenarians (ages ≥95) living in a rural area of South Korea. METHODS: A total of 101 participants were enrolled from four different regions (Gurye, Gokseong, Sunchang, and Damyang), known as the Longevity Belt in Korea. Variables assessing physical and mental health, including the results of blood tests, were examined. Factors associated with good subjective health were identified with logistic regression analysis. RESULTS: Fifty-six participants (59.6%) were subjectively healthy among the centenarians and near-centenarians. Logistic regression analysis revealed that depressive mood was the only factor associated with subjective health and was negatively correlated. The regression model explained 39% of the variance in subjective health. CONCLUSIONS: These findings emphasize the importance of mental health at very advanced ages. Because depressive mood negatively correlates with subjective health, more attention is needed to prevent and manage mood symptoms of people of advanced ages, including centenarians.

Protein arginine methyltransferase 1 contributes to the development of allergic rhinitis by promoting the production of epithelial-derived cytokines.

BACKGROUND: Arginine methylation is a posttranslational modification mediated by protein arginine methyltransferases (PRMTs). Although previous studies have shown that PRMT1 contributes to the severity of allergic airway inflammation or asthma, the underlying mechanism is poorly understood. OBJECTIVE: This study aimed to explore the role of PRMT1 and its relevant mechanism in the development of allergic rhinitis (AR). METHODS: The expression levels of PRMTs and cytokines were determined by RT-PCR, and the localization of PRMT1 was determined by immunohistochemistry and confocal microscopy. The levels of house dust mite (HDM)-specific immunoglobulins in serum and of cytokines in nasal lavage fluids were determined by ELISA. PRMT1 inhibition was achieved by siRNA and treatment with the pan PRMT inhibitor arginine N-methyltransferase inhibitor-1. RESULTS: PRMT1 expression was significantly increased in the nasal mucosa of patients and mice with AR. The degree of eosinophilic infiltration in the nasal mucosa was reduced in PRMT1+/- AR mice compared with wild-type mice. PRMT1 haploinsufficiency reduced the levels of HDM-specific immunoglobulins in serum and those of TH2 (IL-4, IL-5, and IL-13) and epithelial (thymic stromal lymphopoietin [TSLP], IL-25, and IL-33) cytokines in the nasal lavage fluids of AR mice. In nasal epithelial cells, HDM and IL-4 cooperate to enhance PRMT1 expression through a mitogen-activated protein kinase-dependent pathway. In addition, PRMT1 was essential for the production of TSLP, IL-25, and IL-33 in response to HDM and IL-4. Arginine N-methyltransferase inhibitor-1 treatment alleviated AR in the mouse model. CONCLUSIONS: PRMT1 plays an important role in AR development by regulating epithelial-derived cytokine production and might be a new therapeutic target for AR.

Phylogenetic tree-based microbiome association test.

MOTIVATION: Ecological patterns of the human microbiota exhibit high inter-subject variation, with few operational taxonomic units (OTUs) shared across individuals. To overcome these issues, non-parametric approaches, such as the Mann-Whitney U-test and Wilcoxon rank-sum test, have often been used to identify OTUs associated with host diseases. However, these approaches only use the ranks of observed relative abundances, leading to information loss, and are associated with high false-negative rates. In this study, we propose a phylogenetic tree-based microbiome association test (TMAT) to analyze the associations between microbiome OTU abundances and disease phenotypes. Phylogenetic trees illustrate patterns of similarity among different OTUs, and TMAT provides an efficient method for utilizing such information for association analyses. The proposed TMAT provides test statistics for each node, which are combined to identify mutations associated with host diseases. RESULTS: Power estimates of TMAT were compared with existing methods using extensive simulations based on real absolute abundances. Simulation studies showed that TMAT preserves the nominal type-1 error rate, and estimates of its statistical power generally outperformed existing methods in the considered scenarios. Furthermore, TMAT can be used to detect phylogenetic mutations associated with host diseases, providing more in-depth insight into bacterial pathology. AVAILABILITY AND IMPLEMENTATION: The 16S rRNA amplicon sequencing metagenomics datasets for colorectal carcinoma and myalgic encephalomyelitis/chronic fatigue syndrome are available from the European Nucleotide Archive (ENA) database under project accession number PRJEB6070 and PRJEB13092, respectively. TMAT was implemented in the R package. Detailed information is available at http://healthstat.snu.ac.kr/software/tmat. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Fms-Like Tyrosine Kinase 3-Independent Dendritic Cells Are Major Mediators of Th2 Immune Responses in Allergen-Induced Asthmatic Mice.

Dendritic cells (DCs) are the main mediators of Th2 immune responses in allergic asthma, and Fms-like tyrosine kinase 3 ligand (Flt3L) is an important growth factor for the development and homeostasis of DCs. This study identified the DC populations that primarily cause the initiation and development of allergic lung inflammation using Fms-like tyrosine kinase 3 (Flt3) knockout (KO) mice with allergen-induced allergic asthma. We observed type 2 allergic lung inflammation with goblet cell hyperplasia in Flt3 KO mice, despite a significant reduction in total DCs, particularly CD103+ DCs, which was barely detected. In addition, bone marrow-derived dendritic cells (BMDCs) from Flt3 KO mice directed Th2 immune responses in vitro, and the adoptive transfer of these BMDCs exacerbated allergic asthma with more marked Th2 responses than that of BMDCs from wild-type (WT) mice. Furthermore, we found that Flt3L regulated the in vitro expression of OX40 ligand (OX40L) in DCs, which is correlated with DC phenotype in in vivo models. In conclusion, we revealed that Flt3-independent CD11b+ DCs direct Th2 responses with the elevated OX40L and are the primary cause of allergic asthma. Our findings suggest that Flt3 is required to control type 2 allergic inflammation.

Cell Seeding Technology for Microarray-Based Quantitative Human Primary Skeletal Muscle Cell Analysis.

Pipetting techniques play a crucial role in obtaining reproducible and reliable results, especially when seeding cells on small target areas, such as on microarrays, biochips or microfabricated cell culture systems. For very rare cells, such as human primary skeletal muscle cells (skMCs), manual (freehand) cell seeding techniques invariably result in nonuniform cell spreading and heterogeneous cell densities, giving rise to undesirable variations in myogenesis and differentiation. To prevent such technique-dependent variation, we have designed and fabricated a simple, low-cost pipet guidance device (PGD), and holder that works with hand-held pipettes. This work validates the accuracy and reproducibility of the PGD platform and compares its effectiveness with manual and robotic seeding techniques. The PGD system ensures reproducibility of cell seeding, comparable to that of more expensive robotic dispensing systems, resulting in a high degree of cell uniformity and homogeneous cell densities, while also enabling cell community studies. As compared to freehand pipetting, PGD-assisted seeding of C2C12 mouse myoblasts showed 5.3 times more myotube formation and likewise myotubes derived from PGD-seeded human primary skMCs were 3.6 times thicker and 2.2 times longer. These results show that this novel, yet simple PGD-assisted pipetting technique provides precise cell seeding on small targets, ensuring reproducible and reliable high-throughput cell assays.

Chemical screening identifies ATM as a target for alleviating senescence.

Senescence, defined as irreversible cell-cycle arrest, is the main driving force of aging and age-related diseases. Here, we performed high-throughput screening to identify compounds that alleviate senescence and identified the ataxia telangiectasia mutated (ATM) inhibitor KU-60019 as an effective agent. To elucidate the mechanism underlying ATM's role in senescence, we performed a yeast two-hybrid screen and found that ATM interacted with the vacuolar ATPase V1 subunits ATP6V1E1 and ATP6V1G1. Specifically, ATM decreased E-G dimerization through direct phosphorylation of ATP6V1G1. Attenuation of ATM activity restored the dimerization, thus consequently facilitating assembly of the V1 and V0 domains with concomitant reacidification of the lysosome. In turn, this reacidification induced the functional recovery of the lysosome/autophagy system and was coupled with mitochondrial functional recovery and metabolic reprogramming. Together, our data reveal a new mechanism through which senescence is controlled by the lysosomal-mitochondrial axis, whose function is modulated by the fine-tuning of ATM activity.

Multiple airborne allergen-induced eosinophilic chronic rhinosinusitis murine model.

PURPOSE: Several murine models have been established to mimic human eosinophilic chronic rhinosinusitis (ECRS). However, in most of these models, ECRS was induced using ovalbumin, which does not cause sinusitis in humans. Thus, we aimed to develop a more clinically relevant murine model of ECRS using multiple airborne allergens. We also investigated the effects of exposure duration of the allergens on ECRS development. METHODS: C57BL/6 mice were intranasally administered multiple airborne allergens (house dust mite, Aspergillus fumigatus, Alternaria alternata, and protease from Staphylococcus aureus) three times weekly for 4, 8, 12, and 16 consecutive weeks. Histopathological changes, the levels of cytokines and chemokines in the nasal lavage fluid, and immune cells of the blood and spleen were analyzed. RESULTS: The mice administered multiple allergens showed significantly increased eosinophil infiltration, epithelial thickening and disruption, and subepithelial collagen deposition from 8 weeks compared to the control group. Goblet cell hyperplasia, polyp-like lesions, and blood eosinophils, as well as the levels of interleukin-5 and eotaxin in the nasal lavage fluid were considerably increased in the ECRS group from 12 weeks compared to those of controls. Instillation of allergens for 16 weeks exacerbated the eosinophil infiltration and eotaxin increase in the nasal lavage fluid. CONCLUSIONS: We successfully established a new murine model of ECRS using more clinically relevant multiple airborne allergens. Prolonged exposure to airborne allergens for 12 weeks or more, corresponding to the definition of human ECRS, strongly induced eosinophil infiltration as well as epithelial remodeling.

Geographic and demographic variations of inhalant allergen sensitization in Koreans and non-Koreans.

BACKGROUND: To diagnose and treat respiratory allergic diseases, it is important to identify the specific allergens involved. Many differences exist between common inhalant allergens depending on the residential environment and demographic factors. This study aimed to compare common inhalant allergens between Koreans and non-Koreans according to their residential region, age, and sex. METHODS: This study evaluated 15,334 individuals who underwent serum tests for multiple allergen-specific immunoglobulin E at a tertiary academic medical center between January 2010 and December 2016. The individuals included 14,786 Koreans and 548 non-Koreans. The AdvanSure™ Allostation assay (LG Life Science, Korea) was used to test for 33 inhalant allergens. RESULTS: The house dust mite (HDM) was the most common allergen in both Koreans and non-Koreans, although the proportion of individuals with HDM sensitization was greater among Koreans. High sensitization rates for various pollen types were detected among Koreans in Gangwon region, whereas Japanese cedar pollen was unique among Koreans in Jeju region. Grass pollen and animal dander were relatively common among individuals from the Americas, whereas weed and grass pollen accounted for the 10 most common allergens for individuals from Central Asia. The total sensitization rate, sensitization to HDM, and sensitization to animal dander peaked among adolescents and young adults, then subsequently decreased with age. CONCLUSIONS: This large-scale study demonstrates that various regional and age-related differences exist in the allergen sensitization rates of Koreans and non-Koreans. These data could be useful for development of avoidance measures, immunotherapy for causative allergens, and policymaking regarding allergic diseases.

Fibroblast growth factor-1 as a mediator of paracrine effects of canine adipose tissue-derived mesenchymal stem cells on in vitro-induced insulin resistance models.

BACKGROUND: In the field of diabetes research, many studies on cell therapy have been conducted using mesenchymal stem cells. This research was intended to shed light on the influence of canine adipose-tissue-derived mesenchymal stem cell conditioned medium (cAT-MSC CM) on in vitro insulin resistance models that were induced in differentiated 3T3-L1 adipocytes and the possible mechanisms involved in the phenomenon. RESULTS: Gene expression levels of insulin receptor substrate-1 (IRS-1) and glucose transporter type 4 (GLUT4) were used as indicators of insulin resistance. Relative protein expression levels of IRS-1 and GLUT4 were augmented in the cAT-MSC CM treatment group compared to insulin resistance models, indicating beneficial effects of cAT-MSC to DM, probably by actions of secreting factors. With reference to previous studies on fibroblast growth factor-1 (FGF1), we proposed FGF1 as a key contributing factor to the mechanism of action. We added anti-FGF1 neutralizing antibody to the CM-treated insulin resistance models. As a result, significantly diminished protein levels of IRS-1 and GLUT4 were observed, supporting our assumption. Similar results were observed in glucose uptake assay. CONCLUSIONS: Accordingly, this study advocated the potential of FGF-1 from cAT-MSC CM as an alternative insulin sensitizer and discovered a signalling factor associated with the paracrine effects of cAT-MSC.

Surgical outcomes of overlapping lateral pharyngoplasty with or without coblator tongue base resection for obstructive sleep apnea.

PURPOSE: Considerable number of patients with obstructive sleep apnea (OSA) failed to respond to positive airway pressure therapy and so turned to surgical procedures. A wide variety of surgical procedures have been developed and advanced, according to obstruction and target site through nasal cavity to trachea. We introduced our overlapping lateral pharyngoplasty (OLP) technique as a surgical option for OSA and evaluated its surgical outcomes both with and without endoscope-guided coblator tongue base resection (CobTBR). METHODS: Sixty-five patients underwent either OLP alone or OLP combined with CobTBR to treat OSA at academic tertiary center. Twenty-nine patients underwent postoperative polysomnography and were divided into two groups, as an OLP group and an OLP combined CobTBR group. Various parameters from physical examinations and polysomnographic results were compared and analyzed. RESULTS: Most enrolled patients improved on various polysomnographic parameters, including AHI and oxygen levels. In the OLP group, 91.7% of patients showed a surgical response and the overall success rate was 66.7%. Mean AHI improved significantly from 36.3 to 14.8. In the OLP + CobTBR group, all patients showed improvement in AHI and the surgical response rate was 100%. The overall success rate was 70.6% and mean AHI improved from 38.8 to 13.1. In both groups, various parameters such as RDI, lowest O2 saturation, mean O2 saturation, oxygen desaturation index, supine AHI, and ESS significantly improved after surgery. CONCLUSION: Our OLP technique appears to be safe and effective among OSA patients. Multi-level OLP surgery combined with CobTBR can be a good surgical strategy for patients experiencing retroglossal obstruction.

Predictors of success in combination of tongue base resection and lateral pharyngoplasty for obstructive sleep apnea.

The base of the tongue has been recognized as a significant site of obstruction in patients with obstructive sleep apnea (OSA). Our aim was to determine the independent predictors of surgical success in tongue base resection combined with lateral pharyngoplasty for OSA. Thirty-one OSA patients who underwent endoscopie-guided coblator or transoral robotic tongue base resection in combination with lateral pharyngoplasty for the treatment of retroglossal obstruction between March 2012 and December 2015 were enrolled in this study. Retroglossal obstruction was identified by preoperative nasopharyngoscopy with drug-induced sleep endoscopy and/or Müller's maneuver in supine position. Patients were divided into success and failure groups according to surgical outcome (postoperative apnea-hypopnea index (AHI) less than 20 and reduction more than 50% in baseline AHI). Physical profile, polysomnography, cephalometry parameters, and drug-induced sleep endoscopy and/or Müller's maneuver findings were compared between the two groups. Tonsil grade (p = 0.002), lateral oropharyngeal wall collapse on Müller's maneuver (p = 0.002), and AHI during rapid eye movement (REM AHI) (p = 0.038) were significantly higher in the success group than in the failure group. Tongue base collapse was more evident in the failure group than in the success group when patients open their mouth. (p = 0.037) Bigger tonsil size and higher REM AHI are favorable predictive factors, even in multilevel surgery such as tongue base resection, whereas tongue base collapse during mouth opening may be an unfavorable predictive factor.

Transcription factor Sp1 prevents TRF2(ΔBΔM)-induced premature senescence in human diploid fibroblasts.

Telomere uncapping is thought to be the fundamental cause of replicative cellular senescence, but the cellular machineries mediating this process have not been fully understood. In the present study, we present the role of Sp1 transcription factor in the state of telomere uncapping using the TRF2(ΔBΔM)-induced senescence model in human diploid fibroblasts. We observed that the expression of Sp1 is down-regulated in the TRF2(ΔBΔM)-induced senescence, which was mediated by ATM and p38 MAPK. In addition, overexpression of Sp1 prevented the TRF2(ΔBΔM)-induced senescence. Among transcriptional targets of Sp1, expression levels of nuclear transport genes such as karyopherin α, Nup107, and Nup50 were down-regulated in the TRF2(ΔBΔM)-induced senescence, which was prevented by Sp1 overexpression. Moreover, inhibition of the nuclear transport by wheat germ agglutinin (an import inhibitor) and leptomycin B (an export inhibitor) induced premature senescence. These results suggest that Sp1 is an anti-senescence transcription factor in the telomere uncapping-induced senescence and that down-regulation of Sp1 leads to the senescence via down-regulation of the nuclear transport.

Analysis of the Maillard reaction in human hair using Fourier transform infrared spectroscopic imaging and a focal-plane array detector.

The Maillard reaction has been well researched and used in the food industry and the fields of environmental science and organic chemistry. Here, we induced the Maillard reaction inside human hair and analyzed its effects by using Fourier transform infrared spectroscopy with a focal-plane array (FTIR-FPA) detector. We used arginine (A), glycine (G), and D-xylose (X) to generate the Maillard reaction by dissolving them in purified water and heating it to 150 °C. This label-free process generated a complex compound (named AGX after its ingredients) with a monomer structure, which was determined by using nuclear magnetic resonance (NMR) and FTIR-FPA. This compound was stable in hair and substantially increased its tensile strength. To our knowledge, we are the first to report the formation of this monomer in human hair, and our study provides insights into a new method that could be used to improve the condition of damaged or aging hair.

Antibodies to the DNA-directed RNA polymerase II subunit RPB1 occur with highest frequency in centenarians.

BACKGROUND: Recently, phage display technology has made it possible to define the circulating repertoire of humoral immunity. This study was designed to define the circulating antibodies specific to centenarians. RESULTS: We used a phage-displayed combinatorial peptide library to screen for peptides (YSATLRY and YSPTLFY) that preferentially react with the IgG fraction of centenarians aged 100-105 years. Centenarian sera binds to YSATLRY and YSPTLFY with higher frequency than that of healthy volunteers aged 60-79 years or healthy volunteers younger than or equal to 43 years of age. We prepared polyclonal antibodies to YSATLRY from human sera to immunoprecipitate the native antigen, which was identified as the carboxy-terminal domain (CTD) of DNA-directed RNA polymerase II subunit RPB1. The RBP1 CTD contains multiple YSPTSPS repeats, which are significantly homologous to YSATLRY and YSPTLFY. The immunoprecipitated RPB1 had significantly slower mobility than did RPB1 in cell lysates, and the polyclonal antibodies reacted with CTD peptide, depending on the phosphorylation pattern. Therefore, it appears that the polyclonal antibodies preferentially bind to highly phosphorylated RPB1. We also confirmed that human monoclonal antibodies reactive to both YSATLRY and YSPTLFY bound to the phosphorylated YSPTSPS motif. CONCLUSIONS: This study showed that centenarians possess IgG antibodies that are reactive to YSATLRY and YSPTLFY, mimicking the phosphorylated form of the YSPTSPS motif (CTD of RPB1), at a much higher frequency than that of the average population.

Method to purify and analyze heterogeneous senescent cell populations using a microfluidic filter with uniform fluidic profile.

To precisely purify and study aged (senescent) cells, we have designed, fabricated, and demonstrated a novel diamond-structure (DS) microfluidic filter. Nonuniform flow velocities within the microfilter channel can compromise microfluidic filter performance, but with this new diamond structure, further optimized via simulation, we achieve a uniform microfilter flow field, improving the throughput of size-based separation of senescent cells, as obtained by 39-passaged human dermal fibroblasts. After separating these aged cells into two groups, consisting of large- and small-sized cells, we assessed senescence by measuring lipofuscin accumulation and ß-galactosidase activity. Our results reveal that even though these senescent cells had been equivalently passaged in culture, a high degree of size distribution and senescent phenotype heterogeneity was observed. In particular, the smaller-sized cells tended to express a younger phenotype while the larger aged cells demonstrated an older phenotype. We suggest that size-based separation of senescent cells, subtyped into small- and large-sized cohorts, offers an alternative method to purify such aged cells, thereby enabling more precise study of the mechanisms of aging, autophagy impairment, and rejuvenation.

Construction and characterization of Cu²âº, Ni²âº, Zn²âº, and Co²âº modified-DNA crystals.

We studied the physical characteristics of modified-DNA (M-DNA) double crossover crystals fabricated via substrate-assisted growth with various concentrations of four different divalent metallic ions, Cu(2+), Ni(2+), Zn(2+), and Co(2+). Atomic force microscopy (AFM) was used to test the stability of the M-DNA crystals with different metal ion concentrations. The AFM images show that M-DNA crystals formed without deformation at up to the critical concentrations of 6 mM of [Cu(2+)], 1.5 mM of [Ni(2+)], 1 mM of [Zn(2+)], and 1 mM of [Co(2+)]. Above these critical concentrations, the M-DNA crystals exhibited deformed, amorphous structures. Raman spectroscopy was then used to identify the preference of the metal ion coordinate sites. The intensities of the Raman bands gradually decreased as the concentration of the metal ions increased, and when the metal ion concentrations increased beyond the critical values, the Raman band of the amorphous M-DNA was significantly suppressed. The metal ions had a preferential binding order in the DNA molecules with G-C and A-T base pairs followed by the phosphate backbone. A two-probe station was used to measure the electrical current-voltage properties of the crystals which indicated that the maximum currents of the M-DNA complexes could be achieved at around the critical concentration of each ion. We expect that the functionalized ion-doped M-DNA crystals will allow for efficient devices and sensors to be fabricated in the near future.

Has competition increased hospital technical efficiency?

Hospital competition and managed care have affected the hospital industry in various ways including technical efficiency. Hospital efficiency has become an important topic, and it is important to properly measure hospital efficiency in order to evaluate the impact of policies on the hospital industry. The primary independent variable is hospital competition. By using the 2001-2004 inpatient discharge data from Florida, we calculate the degree of hospital competition in Florida for 4 years. Hospital efficiency scores are developed using the Data Envelopment Analysis and by using the selected input and output variables from the American Hospital Association's Annual Survey of Hospitals for those acute care general hospitals in Florida. By using the hospital efficiency score as a dependent variable, we analyze the effects of hospital competition on hospital efficiency from 2001 to 2004 and find that when a hospital was located in a less competitive market in 2003, its technical efficiency score was lower than those in a more competitive market.

Vutiglabridin Alleviates Cellular Senescence with Metabolic Regulation and Circadian Clock in Human Dermal Fibroblasts.

The process of cellular senescence, which is characterized by stable cell cycle arrest, is strongly associated with dysfunctional cellular metabolism and circadian rhythmicity, both of which are reported to result from and also be causal to cellular senescence. As a result, modifying any of them-senescence, metabolism, or the circadian clock-may affect all three simultaneously. Obesity accelerates aging by disrupting the homeostasis of reactive oxygen species (ROS) via an increased mitochondrial burden of fatty acid oxidation. As a result, if senescence, metabolism, and circadian rhythm are all linked, anti-obesity treatments may improve metabolic regulation while also alleviating senescence and circadian rhythm. Vutiglabridin is a small molecule in clinical trials that improves obesity by enhancing mitochondrial function. We found that chronic treatment of senescent primary human dermal fibroblasts (HDFs) with vutiglabridin alleviates all investigated markers of cellular senescence (SA-ß-gal, CDKN1A, CDKN2A) and dysfunctional cellular circadian rhythm (BMAL1) while remarkably preventing the alterations of mitochondrial function and structure that occur during the process of cellular senescence. Our results demonstrate the significant senescence-alleviating effects of vutiglabridin, specifically with the restoration of cellular circadian rhythmicity and metabolic regulation. These data support the potential development of vutiglabridin against aging-associated diseases and corroborate the intricate link between cellular senescence, metabolism, and the circadian clock.

Redox Regulation of PTEN by Reactive Oxygen Species: Its Role in Physiological Processes.

Phosphatase and tensin homolog (PTEN) is a tumor suppressor due to its ability to regulate cell survival, growth, and proliferation by downregulating the PI3K/AKT signaling pathway. In addition, PTEN plays an essential role in other physiological events associated with cell growth demands, such as ischemia-reperfusion, nerve injury, and immune responsiveness. Therefore, recently, PTEN inhibition has emerged as a potential therapeutic intervention in these situations. Increasing evidence demonstrates that reactive oxygen species (ROS), especially hydrogen peroxide (H2O2), are produced and required for the signaling in many important cellular processes under such physiological conditions. ROS have been shown to oxidize PTEN at the cysteine residue of its active site, consequently inhibiting its function. Herein, we provide an overview of studies that highlight the role of the oxidative inhibition of PTEN in physiological processes.