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INTRODUCTION: Premature rupture of membranes (PROM) is defined as rupture of fetal membranes before the onset of labor. Prolactin (PRL) is secreted by decidual membranes and accumulated significantly in the amniotic fluid during pregnancy. PRL could ameliorate inflammation and collagen degradation in fetal membranes. However, the role of PRL in amniotic membrane is not well characterized. METHODS: We isolated human amniotic epithelial stem cells (hAESCs) from human fetal membranes to study the effect of PRL on proliferation, migration, and anti-oxidative stress. Amniotic pore culture technique (APCT) model was constructed to evaluate the tissue regeneration effect in vitro. The potential targets and pathways of PRL acting in amnion via integrated bioinformatic methods. RESULTS: PRL had a dose-dependent effect on hAESCs in vitro. 500 ng/mL PRL significantly improved the viability of hAESCs and inhibited cell apoptosis, related to the up-regulation of CCN2 expression and down-regulation of Bax, Caspase 3, and Caspase 8. PRL accelerated migration process in hAESCs via down-regulation of MMP2, MMP3, and MMP9. PRL attenuated the cellular damage and mitochondrial dysfunction induced by hydrogen peroxide in hAESCs. PRL accelerated the healing process in the APCT model significantly. Top ten specific targets (IGF1R, SIRT1, MAP2K1, CASP8, MAPK14, MCL1, NFKB1, HIF1A, MTOR, and HSP90AA1) and signaling pathways (such as HIF signaling pathway) were selected using an integrated bioinformatics approach. CONCLUSION: PRL improves the viability and anti-oxidative stress function of hAESCs and the regeneration of ruptured amniotic membranes in vitro. Thus, PRL has great therapeutic potential for prevention and treatment of ruptured membranes.
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Bioelectronic implants delivering electrical stimulation offer an attractive alternative to traditional pharmaceuticals in electrotherapy. However, achieving simple, rapid, and cost-effective personalization of these implants for customized treatment in unique clinical and physical scenarios presents a substantial challenge. This challenge is further compounded by the need to ensure safety and minimal invasiveness, requiring essential attributes such as flexibility, biocompatibility, lightness, biodegradability, and wireless stimulation capability. Here, a flexible, biodegradable bioelectronic paper with homogeneously distributed wireless stimulation functionality for simple personalization of bioelectronic implants is introduced. The bioelectronic paper synergistically combines i) lead-free magnetoelectric nanoparticles (MENs) that facilitate electrical stimulation in response to external magnetic field and ii) flexible and biodegradable nanofibers (NFs) that enable localization of MENs for high-selectivity stimulation, oxygen/nutrient permeation, cell orientation modulation, and biodegradation rate control. The effectiveness of wireless electrical stimulation in vitro through enhanced neuronal differentiation of neuron-like PC12 cells and the controllability of their microstructural orientation are shown. Also, scalability, design flexibility, and rapid customizability of the bioelectronic paper are shown by creating various 3D macrostructures using simple paper crafting techniques such as cutting and folding. This platform holds promise for simple and rapid personalization of temporary bioelectronic implants for minimally invasive wireless stimulation therapies.
Subject(s)
Absorbable Implants , Magnetics , Precision Medicine , Wireless Technology , Paper , Precision Medicine/instrumentation , Humans , Male , Animals , Rats , Brain , Electronics, Medical/instrumentationABSTRACT
Tissue regeneration is an essential requirement for wound healing and recovery of organs' function. It has been demonstrated that wound healing can be facilitated by activating paracrine signaling mediated by exosomes secreted from stem cells, since exosomes deliver many functional molecules including growth factors (GFs) and neurotrophic factors (NFs) effective for tissue regeneration. In this study, an exosome-rich conditioned medium (ERCM) was collected from human amniotic membrane stem cells (AMSCs) by cultivating the cells under a low oxygen tension (2% O2 and 5% CO2). The contents of GFs and NFs including keratinocyte growth factor, epidermal growth factor, fibroblast growth factor 1, transforming growth factor-ß, and vascular endothelial growth factor responsible for skin regeneration were much higher (10-30 folds) in the ERCM than in normal conditioned medium (NCM). In was found that CM-DiI-labeled exosomes readily entered keratinocytes and fibroblasts, and that ERCM not only facilitated the proliferation of keratinocytes in normal condition, but also protected against H2O2 cytotoxicity. In cell-migration assay, the scratch wound in keratinocyte culture dish was rapidly closed by treatment with ERCM. Such wound-healing effects of ERCM were confirmed in a rat whole skin-excision model: i.e., the wound closure was significantly accelerated, remaining minimal crusts, by topical application of ERCM solution (4 × 109 exosome particles/100 µL) at 4-day intervals. In the wounded skin, the deposition of collagens was enhanced by treatment with ERCM, which was supported by the increased production of collagen-1 and collagen-3. In addition, enhanced angiogenesis in ERCM-treated wounds was confirmed by increased von Willebrand factor (vWF)-positive endothelial cells. The results indicate that ERCM from AMSCs with high concentrations of GFs and NFs improves wound healing through tissue regeneration not only by facilitating keratinocyte proliferation for skin repair, but also activating fibroblasts for extracellular matrix production, in addition to the regulation of angiogenesis and scar tissue formation.
Subject(s)
Endothelial Cells , Exosomes , Humans , Rats , Animals , Culture Media, Conditioned/pharmacology , Culture Media, Conditioned/metabolism , Endothelial Cells/metabolism , Exosomes/metabolism , Vascular Endothelial Growth Factor A/metabolism , Amnion/metabolism , Angiogenesis , Hydrogen Peroxide/pharmacology , Wound Healing/physiology , Stem Cells , Collagen/pharmacology , Epidermal Growth Factor/pharmacologyABSTRACT
PURPOSE: The purpose of this study was to investigate the relationship between digital literacy and depressive symptoms, as well as the mediating role of social support in this relationship, among older women (60 years and older) in Korea. METHODS: This study analyzed data from the User Experience Evaluation Survey, which was conducted by the Ewha Institute for Age Integration Research to improve the accessibility of digital information for older adults research from May to September 2020. Survey data on depressive symptoms, digital literacy, and social support were analyzed using descriptive statistics, Pearson correlation coefficients, and multiple regression. RESULTS: The factors influencing depressive symptoms among older women included work status (B=-.19, p=.01), social support (B=-.17, p<.001), self-rated health (B=-.13, p=.003), and digital literacy (B=-.10, p=.005), which had an explanatory power of 33%. In addition, social support played a mediating role in the relationship between digital literacy and depressive symptoms (B= -.05, SE=.02; 95% CI, -.09 to -.02). CONCLUSION: The findings of this study support the need to develop and apply interventions that promote digital literacy among older women to mitigate depressive symptoms by increasing social support.
Subject(s)
Depression , Health Literacy , Humans , Female , Aged , Depression/epidemiology , Mediation Analysis , Social Support , Republic of Korea/epidemiologyABSTRACT
Women experiencing primary ovarian insufficiency (POI) are more likely to experience infertility, and its incidence is increasing worldwide annually. Recently, the role of alpha-lipoic acid (ALA) in the treatment of POI has been reported. However, details of the potential pharmacological targets and related molecular pathways of ALA remain unclear and need to be elucidated. Thus, this study aims to elucidate the potential therapeutic target and related molecular mechanism of ALA on POI. First, the potential targets of POI and ALA-related targets were downloaded from online public databases. Subsequently, the overlapped target genes between POI and ALA were acquired, and gene ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG) analysis, protein-protein interaction (PPI) networks were performed and constructed. Finally, molecular docking was performed to verify protein-to-protein effect. A total of 152 potential therapeutic targets were identified. The biological processes of the intersecting targets were mainly involved in the cellular response to peptides, response to xenobiotic stimuli, and response to peptide hormones. The highly enriched pathways were the cAMP, PI3K/AKT, estrogen, progesterone mediated oocyte maturation, and apoptosis signaling pathways. The top 10 hub targets for ALA in the treatment of POI were STAT3, STAT1, CASP3, MTOR, PTGS2, CASP8, HSP90AA1, PIK3CA, MAPK1, and ESR1. The binding between ALA and all top hub targets were verified using the molecular docking analysis. In summary, using the systematic integrated pharmacology network and bioinformatics analysis, this study illustrated that ALA participates in the treatment of POI via multiple targets and multiple pathways mechanisms.
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Glaucoma is one of the most devastating eye diseases, since the disease can develop into blindness and no effective therapeutics are available. Although the exact mechanisms and causes of glaucoma are unknown, increased intraocular pressure (IOP) has been demonstrated to be an important risk factor. Exosomes are lipid nanoparticles secreted from functional cells, including stem cells, and have been found to contain diverse functional molecules that control body function, inhibit inflammation, protect and regenerate cells, and restore damaged tissues. In the present study, exosome-rich conditioned media (ERCMs) were attained via hypoxic culture (2% O2) of human amniotic membrane mesenchymal stem cells (AMMSCs) and amniotic membrane epithelial stem cells (AMESCs) containing 50 times more exosome particles than normoxic culture (20% O2) medium (NCM). The exosome particles in ERCM were confirmed to be 77 nm in mean size and contain much greater amounts of growth factors (GFs) and neurotrophic factors (NFs) than those in NCM. The glaucoma-therapeutic effects of ERCMs were assessed in retinal cells and a hypertonic (1.8 M) saline-induced high-IOP animal model. CM-DiI-labeled AMMSC exosomes were found to readily penetrate the normal and H2O2-damaged retinal ganglion cells (RGCs), and AMMSC-ERCM not only facilitated retinal pigment epithelial cell (RPEC) proliferation but also protected against H2O2- and hypoxia-induced RPEC insults. The IOP of rats challenged with 1.8 M saline increased twice the normal IOP (12-17 mmHg) in a week. However, intravitreal injection of AMMSC-ERCM or AMESC-ERCM (3.9-4.5 × 108 exosomes in 10 µL/eye) markedly recovered the IOP to normal level in 2 weeks, similar to the effect achieved with platelet-derived growth factor-AB (PDGF-AB, 1.5 µg), a reference material. In addition, AMMSC-ERCM, AMESC-ERCM, and PDGF-AB significantly reversed the shrinkage of retinal layers, preserved RGCs, and prevented neural injury in the glaucoma eyes. It was confirmed that stem cell ERCMs containing large numbers of functional molecules such as GFs and NFs improved glaucoma by protecting retinal cells against oxidative and hypoxic injuries in vitro and by recovering IOP and retinal degeneration in vivo. Therefore, it is suggested that stem cell ERCMs could be a promising candidate for the therapy of glaucoma.
Subject(s)
Exosomes , Glaucoma , Rats , Humans , Animals , Intraocular Pressure , Culture Media, Conditioned/pharmacology , Culture Media, Conditioned/metabolism , Exosomes/metabolism , Amnion/metabolism , Hydrogen Peroxide/metabolism , Glaucoma/metabolism , Retina/metabolism , Nerve Growth Factors/metabolism , Stem Cells/metabolism , Disease Models, AnimalABSTRACT
INTRODUCTION: Disruption of fetal membranes before the onset of labor is referred to as premature rupture of membranes (PROM). Lack of maternal folic acid (FA) supplementation reportedly leads to PROM. However, there is a lack of information on the location of FA receptors in the amniotic tissue. Additionally, the regulatory role and potential molecular targets of FA in PROM in vitro have rarely been investigated. METHODS: The three FA receptors (folate receptor α isoform [FRα], transporter of reduced folate [RFC], and proton-coupled folate transporter [PCFT]) in human amniotic epithelial stem cells (hAESCs) and amniotic tissue were localized using immunohistochemistry and immunocytochemistry staining. Effect and mechanism analyses of FA were performed in hAESCs and amniotic pore culture technique (APCT) models. An integrated pharmacological-bioinformatics approach was utilized to explore the potential targets of FA for the treatment of PROM. RESULTS: The three FA receptors were widely expressed in human amniotic tissue, especially in the hAESC cytoplasm. FA stimulated the amnion regeneration in the in vitro APCT model. This mimics the PROM status, in which cystathionine-ß-synthase, an FA metabolite enzyme, may play an important role. The top ten hub targets (STAT1, mTOR, PIK3R1, PTPN11, PDGFRB, ABL1, CXCR4, NFKB1, HDAC1, and HDAC2) of FA for preventing PROM were identified using an integrated pharmacological-bioinformatic approach. DISCUSSION: FRα, RFC, and PCFT are widely expressed in human amniotic tissue and hAESCs. FA aids the healing of ruptured membrane.
Subject(s)
Amnion , Fetal Membranes, Premature Rupture , Female , Humans , Amnion/metabolism , Folic Acid/pharmacology , Fetal Membranes, Premature Rupture/metabolism , Stem CellsABSTRACT
Stretchable sensors based on conductive hydrogels have attracted considerable attention for wearable electronics. However, their practical applications have been limited by the low sensitivity, high hysteresis, and long response times of the hydrogels. In this study, we developed high-performance poly(vinyl alcohol) (PVA)/poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) based hydrogels post-treated with NaCl, which showed excellent mechanical properties, fast electrical response, and ultralow hysteresis properties. The hydrogels also demonstrated excellent self-healing properties with electrical and mechanical properties comparable to those of the original hydrogel and more than 150% elongation at break after the self-healing process. The high performance of the optimized hydrogels was attributed to the enhanced intermolecular forces between the PVA matrix and PEDOT:PSS, the favorable conformational change of the PEDOT chains, and an increase in localized charges in the hydrogel networks. The hydrogel sensors were capable of tracking large human motion and subtle muscle action in real time with high sensitivity, a fast response time (0.88 s), and low power consumption (<180 µW). Moreover, the sensor was able to monitor human respiration due to chemical changes in the hydrogel. These highly robust, stretchable, conductive, and self-healing PVA/PEDOT:PSS hydrogels, therefore, show great application potential as wearable sensors for monitoring human activity.
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Further optimization of perovskite light-emitting diodes (PeLEDs) is impeded by crystal deformation caused by residual stress and defect formation with subsequent non-radiative recombination. Molecular additives for defect passivation are widely studied; however, the majority have insulating properties that hinder charge injection and transport. Herein, highly efficient green-emitting PeLEDs are reported by introducing semiconducting molecular additives (Fl-OEGA and Fl-C8A). Transmission electron microscopy shows that conjugated additives exist primarily at the grain boundaries of perovskite, and Kelvin probe force microscopy confirms that the variation in contact potential difference between grain boundaries and perovskite crystal domains is significantly reduced. The residual tensile stress is reduced by 13% and the activation energy for ion migration increases in the Fl-OEGA-treated perovskite film, compared to those of the film without additives. Compared to insulating 2,2'-(ethylenedioxy)diethylamine (EDEA), the introduction of semiconducting additives prevents a significant reduction in the charge-transport capability. Furthermore, the PeLEDs with Fl-OEGA show a negligible shift in the turn-on voltage and a significantly smaller decrease in the current density with increasing Fl-OEGA compared to the devices with EDEA. Finally, the 3D CsPbBr3 -PeLEDs show the highest external quantum efficiency of 21.3% by the incorporation of semiconducting Fl-OEGA as a new multifunctional additive.
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Impaired calcium uptake resulting from reduced expression and activity of the cardiac sarco-endoplasmic reticulum Ca2+ ATPase (SERCA2a) is a hallmark of heart failure (HF). Recently, new mechanisms of SERCA2a regulation, including post-translational modifications (PTMs), have emerged. Our latest analysis of SERCA2a PTMs has identified lysine acetylation as another PTM which might play a significant role in regulating SERCA2a activity. SERCA2a is acetylated, and that acetylation is more prominent in failing human hearts. In this study, we confirmed that p300 interacts with and acetylates SERCA2a in cardiac tissues. Several lysine residues in SERCA2a modulated by p300 were identified using in vitro acetylation assay. Analysis of in vitro acetylated SERCA2a revealed several lysine residues in SERCA2a susceptible to acetylation by p300. Among them, SERCA2a Lys514 (K514) was confirmed to be essential for SERCA2a activity and stability using an acetylated mimicking mutant. Finally, the reintroduction of an acetyl-mimicking mutant of SERCA2a (K514Q) into SERCA2 knockout cardiomyocytes resulted in deteriorated cardiomyocyte function. Taken together, our data demonstrated that p300-mediated acetylation of SERCA2a is a critical PTM that decreases the pump's function and contributes to cardiac impairment in HF. SERCA2a acetylation can be targeted for therapeutic aims for the treatment of HF.
Subject(s)
Heart Failure , Protein Processing, Post-Translational , Sarcoplasmic Reticulum Calcium-Transporting ATPases , p300-CBP Transcription Factors , Humans , Heart Failure/metabolism , Lysine/metabolism , Myocytes, Cardiac/metabolism , p300-CBP Transcription Factors/chemistry , p300-CBP Transcription Factors/metabolism , Sarcoplasmic Reticulum Calcium-Transporting ATPases/metabolismABSTRACT
Defect states at the surface and grain boundaries of perovskite films have been known to be major determinants impairing the optoelectrical properties of perovskite films and the stability of perovskite solar cells (PeSCs). Herein, an n-type conjugated small-molecule additive based on fused-unit dithienothiophen[3,2-b]-pyrrolobenzothiadiazole-core (JY16) is developed for efficient and stable PeSCs, where JY16 possesses the same backbone as the widely used Y6 but with long-linear n-hexadecyl side chains rather than branched side chains. Upon introducing JY16 into the perovskite films, the electron-donating functional groups of JY16 passivate defect states in perovskite films and increase the grain size of perovskite films through Lewis acid-base interactions. Compared to Y6, JY16 exhibits superior charge mobility owing to its molecular packing ability and prevents decomposition of perovskite films under moisture conditions owing to their hydrophobic characteristics, improving the charge extraction ability and moisture stability of PeSCs. Consequently, the PeSC with JY16 shows a high power conversion efficiency of 21.35%, which is higher than those of the PeSC with Y6 (20.12%) and without any additive (18.12%), and outstanding moisture stability under 25% relative humidity, without encapsulation. The proposed organic semiconducting additive will prove to be crucial for achieving highly efficient and moisture stable PeSCs.
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Metal halide perovskites (MHPs) have gained traction as emitters owing to their excellent optical properties, such as facile bandgap tuning, defect tolerance, and high color purity. Nevertheless, blue-emitting MHP light-emitting diodes (LEDs) show only marginal progress in device efficiency compared with green and red LEDs. Herein, the origin of the drop in efficiency of blue-emitting perovskite nanocrystals (PNCs) by mixing halides and the genesis of Ruddlesden-Popper faults (RPFs) in CsPbBrX Cl3-X nanocrystals is investigated. Using scanning transmission electron microscopy and density functional theory calculations, the authors have found that RPFs induce possible nonradiative recombination pathways owing to the high chloride vacancy concentration nearby. The authors further confirm that the blue-emitting PNCs do not show RPFs post-halide exchange in the CsPbBr3 nanocrystals. By introducing the post-halide exchange treatment, high-efficiency pure blue-emitting (464 nm) PNC-based LEDs with an external quantum efficiency of 2.1% and excellent spectral stability with a full-width at half-maximum of 14 nm are obtained.
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Background This study aims to examine the effect of time-variant perceived neighborhood social cohesion, perceived neighborhood physical disorder, and local crime on cardiovascular disease (CVD) incidence from 2006 through 2016. Methods and Results We obtained data from the Health & Retirement Study. Respondents aged ≥50 years and with no recorded history of CVD until 2006 (N=8826) were included and followed for 10 years. Cox proportional hazards models were estimated with CVD incidence as an outcome variable and time-variant social environment factors (perceived neighborhood social cohesion, perceived neighborhood physical disorder, and local crime) as exposures, after controlling for sociodemographic factors and CVD-related risk/protective factors. Our results showed that perceived neighborhood social cohesion was associated with CVD among Black respondents, but not Hispanic and White respondents. Perceived neighborhood physical disorder and local crime rates were not associated with CVD incidence across all racial and ethnic groups. Conclusions The results demonstrate that perceptions of favorable social environments need to be considered to reduce CVD risk among Black adults. Further research is needed to identify different pathways through which living in favorable social environments benefits cardiovascular health by racial and ethnic groups.
Subject(s)
Cardiovascular Diseases , Social Determinants of Health , Adult , Humans , Cardiovascular Diseases/epidemiology , Ethnicity , Racial Groups , Residence Characteristics , Social Environment , United States/epidemiologyABSTRACT
OBJECTIVES: The objective of this study was to evaluate the efficacy of cell therapy using human amniotic epithelial stem cells (hAESCs) for the treatment of premature rupture of membranes (PROM) in vitro. DESIGN: Using the amniotic pore culture technique (APCT), we mimicked the environment of PROM in vitro, thus enabling the observation of the healing process of hAESC-treated amniotic membranes. MATERIALS: Amniotic membrane samples were collected from placentas of pregnant women who underwent elective cesarean sections. APCT model and isolated hAESCs were used in this study. All patients who participated in this study provided their written informed consent prior to the commencement of the study. SETTINGS: To create the APCT model in vitro, isolated amniotic membranes were punched to create 5 mm diameter circles and re-punched to form a 1-mm pore at the center. Membranes were cultured in α-minimal essential medium, and the hAESCs were collected and cultured as well. Subsequently, the APCT models were divided into two groups: hAESC treated and control. METHODS: Within the culture period, pore sizes were calculated to evaluate the degree of tissue regeneration in both groups. We then evaluated the histology, cell density, and epithelial thickness of the regenerated tissues. Statistical analyses were performed using SPSS software ver. 20.0 (IBM, Armonk, NY, USA) with repeated-measures one-way analysis of variance or paired samples t test. The significance level was set at p < 0.05. RESULTS: As per the evaluation of the APCT model in vitro, the pore size in the hAESC-treated group reduced by 62.2% on day 6 (62.2 ± 0.19, n = 24), whereas in the control group, it shrank by only 36.8% (p < 0.05) (36.8 ± 0.19, n = 24). Furthermore, the epithelial thickness in the amniotic epithelial stem cell-treated group (10.08 ± 1.26 µm, n = 8) was significantly higher than that in the control group (5.87 ± 0.94 µm, n = 8). Cell density in the regenerated tissue in the amniotic epithelial stem cell-treated group (57 ± 2.77, n = 8) was significantly higher than that in the control group (49 ± 2.23, n = 8). LIMITATIONS: In this study, we did not explore the molecular mechanisms by which hAESCs participate in membrane healing in the APCT model. Although our results showed a significant difference, this difference was not too obvious. Therefore, further research on the mechanisms of hAESCs is needed, with more amniotic tissues and APCT samples being tested. CONCLUSIONS: We developed an APCT model to investigate the PROM conditions in vitro. By implanting donor hAESCs in the pores of the APCT model, we observed that hAESCs seeding accelerated pore healing in vitro. Thus, hAESCs may be a valuable source of cells for cell therapies in regenerative medicine.
Subject(s)
Fetal Membranes, Premature Rupture , Premature Birth , Infant, Newborn , Humans , Female , Pregnancy , Amnion , Stem Cell Transplantation , Culture Techniques , Fetal Membranes, Premature Rupture/therapy , Amniotic FluidABSTRACT
Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD), which represent the range of dystrophinopathies, account for nearly 80% of muscle dystrophy. DMD and BMD result from the loss of a functional dystrophin protein, and the leading cause of death in these patients is cardiac remodeling and heart failure. The pathogenesis and progression of the more severe form of DMD have been extensively studied and are controlled by many determinants, including microRNAs (miRNAs). The regulatory role of miRNAs in muscle function and the differential miRNA expression in muscular dystrophy indicate the clinical significance of miRNAs. This review discusses the relevant microRNAs as potential biomarkers and therapeutic targets for DMD and DMD cardiomyopathy as examples of dystrophinopathies.
Subject(s)
Cardiomyopathies , MicroRNAs , Muscular Dystrophy, Duchenne , Biomarkers , Cardiomyopathies/genetics , Dystrophin/genetics , Heart , Humans , MicroRNAs/genetics , MicroRNAs/therapeutic use , Muscular Dystrophy, Duchenne/therapyABSTRACT
Post-translational modification of the myofilament protein troponin I by phosphorylation is known to trigger functional changes that support enhanced contraction and relaxation of the heart. We report for the first time that human troponin I can also be modified by SUMOylation at lysine 177. Functionally, TnI SUMOylation is not a factor in the development of passive and maximal force generation in response to calcium, however this modification seems to act indirectly by preventing SUMOylation of other myofilament proteins to alter calcium sensitivity and cooperativity of myofilaments. Utilising a novel, custom SUMO site-specific antibody that recognises only the SUMOylated form of troponin I, we verify that this modification occurs in human heart and that it is upregulated during disease.
Subject(s)
Calcium , Troponin I , Calcium/metabolism , Humans , Lysine/metabolism , Myofibrils/metabolism , Phosphorylation , Sumoylation , Troponin I/genetics , Troponin I/metabolismABSTRACT
Post-translational modification (PTM) is an essential mechanism for enhancing the functional diversity of proteins and adjusting their signaling networks. The reversible conjugation of ubiquitin (Ub) and ubiquitin-like proteins (Ubls) to cellular proteins is among the most prevalent PTM, which modulates various cellular and physiological processes by altering the activity, stability, localization, trafficking, or interaction networks of its target molecules. The Ub/Ubl modification is tightly regulated as a multi-step enzymatic process by enzymes specific to this family. There is growing evidence that the dysregulation of Ub/Ubl modifications is associated with various diseases, providing new targets for drug development. In this review, we summarize the recent progress in understanding the roles and therapeutic targets of the Ub and Ubl systems in the onset and progression of human diseases, including cancer, neurodegenerative disorders, and heart diseases.
Subject(s)
Heart Diseases , Neoplasms , Neurodegenerative Diseases , Ubiquitin , Ubiquitins , Heart Diseases/metabolism , Humans , Neoplasms/metabolism , Neurodegenerative Diseases/metabolism , Protein Processing, Post-Translational , Proteins/metabolism , Ubiquitin/metabolism , Ubiquitins/metabolismABSTRACT
Chest X-ray radiographic (CXR) imagery enables earlier and easier lung disease diagnosis. Therefore, in this paper, we propose a deep learning method using a transfer learning technique to classify lung diseases on CXR images to improve the efficiency and accuracy of computer-aided diagnostic systems' (CADs') diagnostic performance. Our proposed method is a one-step, end-to-end learning, which means that raw CXR images are directly inputted into a deep learning model (EfficientNet v2-M) to extract their meaningful features in identifying disease categories. We experimented using our proposed method on three classes of normal, pneumonia, and pneumothorax of the U.S. National Institutes of Health (NIH) data set, and achieved validation performances of loss = 0.6933, accuracy = 82.15%, sensitivity = 81.40%, and specificity = 91.65%. We also experimented on the Cheonan Soonchunhyang University Hospital (SCH) data set on four classes of normal, pneumonia, pneumothorax, and tuberculosis, and achieved validation performances of loss = 0.7658, accuracy = 82.20%, sensitivity = 81.40%, and specificity = 94.48%; testing accuracy of normal, pneumonia, pneumothorax, and tuberculosis classes was 63.60%, 82.30%, 82.80%, and 89.90%, respectively.
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BACKGROUND: Enzymatic digestion and explant method have been widely used for isolating umbilical cord-derived mesenchymal stem cells (UC MSCs), although there is still a strong need for robust protocols for optimal isolation for large-scale stem cell banks. This study aims to establish an explant method for clinical scale production of MSCs from human UC tissue and to characterize UC MSCs isolated and cultured with the explant method. METHODS: UC MSCs were isolated by enzymatic digestion, minimal cube explant (MCE) 1-2, MCE 2-4, and MCE 10 and cultured, respectively. Also, human antibody array and basic fibroblast growth factor (bFGF) secretion in conditioned medium (CM) was analyzed. The cells were evaluated initial cell number, colony forming unit-fibroblast (CFU-F), proliferation capacity, CD marker expression, and multi-lineage differentiation. SA-ß-gal assay as well as expression of p16, p21 and p53 was performed by RT-PCR. RESULTS: MCE 2-4 is the most optimized method for isolation of small umbilical cord-derived fast proliferating cells (smumf cells) with the greatest number. MCE 2-4 had the highest secretion of various bioactive factors including bFGF. The MCE 2-4 provided significantly higher CD146 expression than enzymatic digestion, and that expression was maintained until P20. The gene expression of p16, p21, and p53 of smumf cells did not change until P10 and SA-ß-gal activity did not increase until P14. CONCLUSION: This study demonstrated that MCE 2-4 provided an optimal environment to isolate MSCs with quantity and quality from human whole UC tissue through secretion of various bioactive factors inherent to UC.
Subject(s)
Mesenchymal Stem Cells , Tumor Suppressor Protein p53 , Cell Differentiation , Cells, Cultured , Humans , Mesenchymal Stem Cells/metabolism , Tumor Suppressor Protein p53/metabolism , Umbilical CordABSTRACT
Stay-at-home orders and public health safety concerns precipitated by the COVID-19 pandemic facilitated rapid changes in policy and reimbursement regulations and resulted in the sudden uptake of telehealth in mental health practices across the United States. This study explored how mental health service providers experienced the use of telehealth in serving their rural clients who are youth and older adults. A purposive sampling strategy was employed to identify and recruit mental health service providers and insurance agency representatives for this study. By means of online focus groups, this statewide study explored the experiences of 147 mental health and public insurance providers using telehealth to serve rural youth and elderly in Pennsylvania amid the pandemic in 2020. NVivo 12 qualitative analysis software was used in data analysis. The findings suggest that telehealth is perceived as both: silver linings during the pandemic (service continuation during the pandemic, improved parental involvement and responsiveness, easing the transportation challenges, and decrease in no-show rates) and some roadblocks to success (Not for every youth!, Technology challenges among the older adults, and "Dead zones" without internet and cellphone reception). Policy and practice recommendations are suggested including incentives for proactive telehealth uptake, telehealth parity laws and reimbursement policies, and incentivizing innovative use of technology for specific populations and therapeutic modalities. Continuous policy support and organizational efforts to provide customized telemental health are called for to remediate rural disparities in access to mental health services beyond the pandemic period.