Novel composite gel polymer electrolytes exhibiting high ionic conductivity and good mechanical stability are prepared, and their electrochemical properties are characterized. As lithium ion sources ...of a single ion conductor, the core‐shell structured SiO2(Li+) nanoparticles with uniform spherical shape are synthesized and used as functional fillers in the composite gel polymer electrolytes. By using the composite gel polymer electrolytes, the lithium powder polymer batteries composed of a lithium powder anode and a layered lithium vanadate (LiV3O8) cathode are assembled and their cycling performance is evaluated. The resulting lithium powder polymer batteries deliver a high discharge capacity of 264 mAh g−1 at room temperature and exhibit good capacity retention even at high current rates. The morphological analysis of the lithium powder anode reveals that the dendrite growth during cycling can be effectively suppressed by using the composite gel polymer electrolytes.
Composite gel polymer electrolytes exhibiting high ionic conductivity and good mechanical stability are prepared and characterized. Core‐shell structured SiO2(Li+) nanoparticles of uniform spherical shape are used as functional fillers in the composite gel polymer electrolytes. Lithium powder polymer batteries composed of a lithium powder anode and a LiV3O8 cathode deliver a high discharge capacity and exhibit good capacity retention.
When individuals face psychological difficulties that exceed their resources, consulting professionals for mental health treatment can be an effective way to overcome these difficulties. However, in ...general, only a few patients receive treatment for depression. The goal of the present study was to explore the help-seeking behaviors of currently employed individuals with depression and the factors influencing their help-seeking behaviors. This study used raw data from the Korean Community Health Survey (KCHS) obtained from 2017 to 2020. A total of 6,505 employed individuals, who responded as having experiences of sadness or hopelessness that caused problems in their lives for more than two weeks and who scored more than nine points on the Patient Health Questionnaire-9, were included in our analysis. Help-seeking behavior was measured as receiving expert advice due to feelings of sadness or hopelessness. Of the 6,505 people with depression, only 1,781 (27.38%) received professional counseling for it. Male participants (adjusted odds ratio aOR = 1.31, 95% confidence interval CI = 1.157-1.487), those aged 45-64 years (aOR = 1.192, 95% CI = 1.022-1.389) and more than 75 years (aOR = 1.446, 95% CI = 1.059-1.973), those not having a Medical Aid program (aOR = 1.750, 95% CI = 1.375-2.226), and those having low educational levels (aOR = .896, 95% CI = .830-.968) were less likely to seek professional help for depression. Our study found that help-seeking behaviors for depression in the Korean population were low. Furthermore, we identified the characteristics associated with individuals with depressive symptoms who chose not to receive help from mental health professionals. The results of this study provide insights to guide national interventions to increase help-seeking behaviors for depression.
Photobiomodulation therapy (PBMT) effects an important role in neural regeneration and function enhancement, such as expression of nerve growth factor and nerve regeneration, in neuronal tissues, and ...inhibition of cell death by amyloid beta in neurons is inhibited by PBMT. However, there no studies evaluated the effects of PBMT on oxidative stress in the hippocampus. The aim of this study is to evaluate the effects of PBMT on oxidative stress in the hippocampus. This study assessed the anti-oxidative effect, the expression of BDNF and antioxidant enzymes, as well as the activation of cAMP response element binding (CREB) and extracellular signal-regulated kinase (ERK) signal transduction pathways assess using a hippocampal cell line (HT-22) and mouse organotypic hippocampal tissues by PBMT (LED, 660 nm, 20 mW/cm
). PBMT inhibited HT-22 cell death by oxidative stress and increased BDNF expression via ERK and CREB signaling pathway activation. In addition, PBMT increased BDNF expression in hippocampal organotypic slices and the levels of phosphorylated ERK and CREB, which were reduced by oxidative stress, as well as the expression of the antioxidant enzyme superoxide dismutase. These data demonstrate that PBMT inhibits hippocampal damage induced by oxidative stress and increases the expression of BDNF, which can be used as an alternative to treat a variety of related disorders that lead to nerve damage. Activation and redox homeostasis in neuronal cells may be a notable mechanism of the 660-nm PBMT-mediated photobioreactivity.
Genipin, a natural compound derived from the fruit of Gardenia jasminoides Ellis, was reported to have activity against various cancer types. In this study, we determined the underlying mechanism for ...genipin‐induced cell death in human oral squamous cell carcinoma (OSCC). The growth‐inhibitory effects of genipin in human OSCC cells was examined by the Cell Counting Kit‐8 and soft agar assays. The effects of genipin on apoptosis were assessed by nuclear morphological changes by 4′,6‐diamidino‐2‐phenylindole staining, measurement of the sub‐G1 population, and Annexin V‐fluorescein isothiocyanate/propidium iodide double staining. The underlying mechanism of genipin activity was analyzed by western blot analysis, subcellular fractionation of the nucleus and cytoplasm, immunocytochemistry, and quantitative real‐time polymerase chain reaction. Genipin inhibited the growth of OSCC cells and induced apoptosis, which was mediated by a caspase‐dependent pathway. Genipin reduced the phosphorylation of signal transducer and activator of transcription 3 (STAT3) at Tyr705 and its nuclear localization. Furthermore, inhibition of p‐STAT3Tyr705 levels following genipin treatment was required for the reduction of survivin and myeloid cell leukemia‐1 (Mcl‐1) expression, leading to apoptotic cell death. The genipin‐mediated reduction in survivin and Mcl‐1 expression was caused by transcriptional and/or posttranslational regulatory mechanisms. The results provide insight into the regulatory mechanism by which genipin induces apoptotic cell death through the abrogation of nuclear STAT3 phosphorylation and suggest that genipin may represent a potential therapeutic option for the treatment of human OSCC.
Significance statement
STAT3 is frequently overexpressed in various cancers, including OSCC, indicating that it can be an oncogenic factor and cancer therapy targeting STAT3 is thought to be a promising therapeutic option.
In the present study, we investigated the possibility of genipin as an anticancer drug candidate by targeting STAT3 kinase in oral cancer cell lines.
The importance of our findings is genipin can mediate STAT3 signaling to induce apoptosis for treating human oral cancer and, to the best our knowledge, it is the first study showing the deactivation of STAT3 by genipin for apoptosis in oral cancer.
Tumor suppressor p53 is not only affects immune responses but also contributes to antibacterial activity. However, its bactericidal function during mycobacterial infection remains unclear. In this ...study, we found that the p53-deficient macrophages failed to control
Mycobacterium tuberculosis
(Mtb), manifested as a lower apoptotic cell death rate and enhanced intracellular survival. The expression levels of p53 during Mtb infection were stronger in M1 macrophages than in M2 macrophages. The TLR2/JNK signaling pathway plays an essential role in the modulation of M1 macrophage polarization upon Mtb infection. It facilitates p53-mediated apoptosis through the production of reactive oxygen species, nitric oxide and inflammatory cytokines in Mtb-infected M1 macrophages. In addition, nutlin-3 effectively abrogated the intracellular survival of mycobacteria in both TB patients and healthy controls after H37Ra infection for 24 h, indicating that the enhancement of p53 production effectively suppressed the intracellular survival of Mtb in hosts. These results suggest that p53 can be a new therapeutic target for TB therapy.
Because of poor engraftment and safety concerns regarding mesenchymal stem cell (MSC) therapy, MSC-derived exosomes have emerged as an alternative cell-free therapy for myocardial infarction (MI). ...However, the diffusion of exosomes out of the infarcted heart following injection and the low productivity limit the potential of clinical applications. Here, we developed exosome-mimetic extracellular nanovesicles (NVs) derived from iron oxide nanoparticles (IONPs)-incorporated MSCs (IONP-MSCs). The retention of injected IONP-MSC-derived NVs (IONP-NVs) within the infarcted heart was markedly augmented by magnetic guidance. Furthermore, IONPs significantly increased the levels of therapeutic molecules in IONP-MSCs and IONP-NVs, which can reduce the concern of low exosome productivity. The injection of IONP-NVs into the infarcted heart and magnetic guidance induced an early shift from the inflammation phase to the reparative phase, reduced apoptosis and fibrosis, and enhanced angiogenesis and cardiac function recovery. This approach can enhance the therapeutic potency of an MSC-derived NV therapy.
In this study, an electrochemical biosensor composed of a horseradish peroxidase (HRP)-encapsulated protein nanoparticles (HEPNP) was fabricated for the sensitive and selective detection of H
2
O
2
. ...The HEPNP has a three-dimensional structure that can contain a large amount of HRP; therefore, HEPNP can amplify the electrochemical signals necessary for the detection of H
2
O
2
. Furthermore, reduced graphene oxide (rGO) was used to increase the efficiency of electron transfer from the HEPNP to an electrode, which could enhance the electrochemical signal. This biosensor showed a sensitive electrochemical performance for detection of H
2
O
2
with signals in the range from 0.01–100 μM, and it could detect low concentrations up to 0.01 μM. Furthermore, this biosensor was operated against interferences from glucose, ascorbic acid, and uric acid. In addition, this fabricated H
2
O
2
biosensor showed selective detection performance in human blood serum. Therefore, the proposed biosensor could promote the sensitive and selective detection of H
2
O
2
in clinical applications.
Background and Aim
Tumor stroma and tumor‐infiltrating lymphocytes (TILs) are major constituents of the tumor microenvironment, although they have different effects on the prognosis of patients with ...colorectal cancer (CRC). Combinatory statuses of tumor‐stromal percentage (TSP) and TILs are expected to provide more powerful prognostic information but have never been studied in CRCs.
Methods
Stage III CRCs from patients (n = 487) treated with adjuvant chemotherapy were assessed for their TSP and CD3‐TIL or CD8‐TIL densities using computer‐aided methodology. With cut‐off values set at median values for intraepithelial TIL (iTIL) and stromal TIL (sTIL) densities, CRCs were sorted into low and high iTIL or sTIL groups. CRCs were classified into five quintile (Q1–Q5) groups according to their TSP and divided into high TSP (Q5) and low TSP (Q1–4) groups.
Results
The combination of CD8 iTIL density and TSP was found to be an independent prognostic parameter in multivariate survival analysis in terms of cancer‐specific survival and recurrence‐free survival. CRCs with low CD8 iTIL density and high TSP showed the worst survival. The combinatory status showed more prognostic power than CD8 iTIL density or TSP alone. Multivariate survival analysis in an independent cohort of stage III CRC validated the prognostic power of the combinatory statuses.
Conclusions
The findings suggest that the combinatory status might serve as a prognostic parameter in stage III CRCs. Further research in a large‐scale cohort of patients with stage III CRC is needed to validate the prognostic power of the combinatory status.
Mycobacterium avium, a slow‐growing nontuberculous mycobacterium, causes fever, diarrhoea, loss of appetite, and weight loss in immunocompromised people. We have proposed that endoplasmic reticulum ...(ER) stress‐mediated apoptosis plays a critical role in removing intracellular mycobacteria. In the present study, we investigated the role of the regulated IRE1‐dependent decay (RIDD) pathway in macrophages during M. avium infection based on its role in the regulation of gene expression. The inositol‐requiring enzyme 1 (IRE1)/apoptosis signal‐regulating kinase 1 (ASK1)/c‐Jun N‐terminal kinase (JNK) signalling pathway was activated in macrophages after infection with M. avium. The expression of RIDD‐associated genes, such as Bloc1s1 and St3gal5, was decreased in M. avium‐infected macrophages. Interestingly, M. avium‐induced apoptosis was significantly suppressed by pretreatment with irestatin (inhibitor of IRE1α) and 4μ8c (RIDD blocker). Macrophages pretreated with N‐acetyl cysteine (NAC) showed decreased levels of reactive oxygen species (ROS), IRE1α, and apoptosis after M. avium infection. The expression of Bloc1s1 and St3gal5 was increased in NAC‐pretreated macrophages following infection with M. avium. Growth of M. avium was significantly increased in irestatin‐, 4μ8c‐, and NAC‐treated macrophages compared with the control. The data indicate that the ROS‐mediated ER stress response induces apoptosis of M. avium‐infected macrophages by activating IRE1α‐RIDD. Thus, activation of IRE1α suppresses the intracellular survival of M. avium in macrophages.
Aims
Spinal cord injury (SCI) above the sacral level causes bladder dysfunction and remodeling with fibrosis. This study examined the antifibrotic effects using nintedanib, an inhibitor of vascular ...endothelial growth factor, fibroblast growth factor, and platelet‐derived growth factor receptors, on detrusor overactivity (DO) and bladder fibrosis, as well as the modulation mechanisms of C‐fiber afferent pathways.
Methods
Thirty female C57BL/6 mice were divided into group A (spinal intact), group B (SCI with vehicle), and group C (SCI with nintedanib). At 2 weeks after SCI, vehicle or 50 mg/kg nintedanib was administered subcutaneously for 2 weeks. Then, cystometry was conducted, followed by RT‐PCR measurements of fibrosis‐related molecules, muscarinic, β‐adrenergic, TRP and purinergic receptors in the bladder or L6‐S1 dorsal root ganglia (DRG). Trichrome stain and Western blot analysis of transforming growth factor‐beta and fibronectin were performed in the bladder. TRPV1 expression in L6 DRG was measured by immunohistochemistry.
Results
In cystometry, intercontraction intervals, nonvoiding contractions, voided volume, and voiding efficiency were significantly improved in group C versus group B. RT‐PCR, Western blotting, and trichrome staining revealed the fibrotic changes in the bladder of group B, which was improved in group C. Increased messenger RNA levels of TRPV1, TRPA1, P2X2, and P2X3 in DRG of group B were significantly decreased in group C. TRPV1 immunoreactivity in DRG was increased in group B, but decreased in group C.
Conclusions
Nintedanib improves storage and voiding dysfunctions and bladder fibrosis in SCI mice. Also, nintedanib‐induced improvement of DO is associated with reduced expression of C‐fiber afferent markers, suggesting the modulation of bladder C‐fiber afferent activity.
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