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Redundancy of cancer cells towards ROS-mediated apoptosis despite expressing proline-rich p66shc abundantly needs to be investigated properly. P66shc, an adapter protein, is indispensable both for initiating ROS-mediated apoptosis and subsequent ROS generation through Rac-1 activation. P66shc gets phosphorylated at Ser-36 that triggers its translocation to the mitochondria and subsequent release of Cytochrome c in response to oxidative stress. It also aids in Rac-1 dependent NADPH oxidase activation, leading to the generation of cytosolic ROS that can perform diverse functions depending on its concentration. This study has identified the multi-faceted anti-apoptotic protein BAG3 as an interacting partner of p66shc. BAG3 utilizes its WW domain to bind to the proline-rich motifs of p66shc. BAG3, through its WW domain, antagonizes p66shc mediated apoptosis, by inhibiting both the expression and phosphorylation of p66shc under normal and oxidative stress conditions. This results in significant protection against ROS-mediated apoptosis. BAG3-mediated reduction in p66shc expression increases cell proliferation and metastasis. The increase in cell proliferation is attributed to the impact of BAG3 on Rac-1 activation and ROS production under normal conditions. This study has unraveled an interactor of p66shc that enhances pro-survival role while simultaneously suppressing its apoptotic role.
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Botulinum toxin A (BONT/A) injections play a central role in the treatment of upper limb spasticity in stroke patients. We proposed structured stretching exercises to enhance the effect of post-stroke spasticity relief of the upper limbs following BONT/A injections. A total of 43 patients who had a stroke with grade 2 spasticity or higher on the Modified Ashworth Scale (MAS) in their upper-limb muscles were randomly assigned to the intervention (n = 21) or control group (n = 22). The former received structured stretching exercises after their BONT/A injections for 20 min, 5 days per week, for 6 months at a hospital, while the others conducted self-stretching exercises at home. The outcome measures were assessed before the intervention (T0) and after three (T1) and six months (T2). Significantly greater improvements in the MAS scores of the elbows, wrists, and fingers were found in the intervention group's patients at T1 and T2. The behavioral outcome measures, including shoulder pain, activities of daily living, and quality of life, and our electrophysiological studies also showed a significantly higher enhancement in this patient group. In conclusion, the structured stretching exercises plus BONT/A injections for six months showed a superior effect in relieving post-stroke upper-limb spasticity compared to self-stretching exercises.
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Toxinas Botulínicas Tipo A , Espasticidad Muscular , Ejercicios de Estiramiento Muscular , Accidente Cerebrovascular , Humanos , Espasticidad Muscular/tratamiento farmacológico , Espasticidad Muscular/etiología , Espasticidad Muscular/terapia , Masculino , Femenino , Persona de Mediana Edad , Accidente Cerebrovascular/complicaciones , Toxinas Botulínicas Tipo A/administración & dosificación , Toxinas Botulínicas Tipo A/uso terapéutico , Anciano , Resultado del Tratamiento , Extremidad Superior , Fármacos Neuromusculares/administración & dosificación , Fármacos Neuromusculares/uso terapéutico , Actividades Cotidianas , Calidad de Vida , Rehabilitación de Accidente Cerebrovascular/métodosRESUMEN
Klotho is an antiaging protein that has multiple functions. The purpose of this study is to investigate whether soluble klotho plays a role in cellular stress response pathways. We found that klotho deficiency (kl-/-) largely decreased HSF1 levels and impaired heat shock protein expression. Interestingly, recombinant soluble klotho-induced HSF1 and HSPs such as HSP90, HSP70, and HSP27 in kl-/- mouse embryonic fibroblasts (MEFs). Soluble Klotho treatment also induced cell proliferation and HSF1 promoter activity in MEF kl-/- cells in a concentration-dependent manner. Furthermore, using point mutagenesis, we identified regulatory/binding sites of transcription factors EGR1 regulated by soluble klotho in the HSF1 promoter. Taken together, our findings unravel the molecular basis of klotho and provide molecular evidence supporting a direct interaction between soluble klotho and HSF1-mediated stress response pathway.
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Seamless integration and conformal contact of soft electronics with tissue surfaces have emerged as major challenges in realizing accurate monitoring of biological signals. However, the mechanical mismatch between the electronics and biological tissues impedes the conformal interfacing between them. Attempts have been made to utilize soft hydrogels as the bioelectronic materials to realize tissue-comfortable bioelectronics. However, hydrogels have several limitations in terms of their electrical and mechanical properties. In this study, we present the development of a 3D-printable modulus-tunable hydrogel with multiple functionalities. The hydrogel has a cross-linked double network, which greatly improves its mechanical properties. Functional fillers such as XLG or functionalized carbon nanotubes (fCNT) can be incorporated into the hydrogel to provide tunable mechanics (Young's modulus of 10-300 kPa) and electrical conductivity (electrical conductivity of â¼20 S/m). The developed hydrogel exhibits stretchability (â¼1000% strain), self-healing ability (within 5 min), toughness (400-731 kJ/m3) viscoelasticity, tissue conformability, and biocompatibility. Upon examining the rheological properties in the modulated region, hydrogels can be 3D printed to customize the shape and design of the bioelectronics. These hydrogels can be fabricated into ring-shaped strain sensors for wearable sensor applications.
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Técnicas Biosensibles , Nanotubos de Carbono , Hidrogeles , Tinta , Conductividad Eléctrica , Electrónica , Impresión TridimensionalRESUMEN
Toe grip strength has recently been suggested to play an essential role in maintaining balance and postural stability for ambulatory function in older populations. This study aimed to investigate its association with improving gait function three months after onset in patients with subacute stroke. This longitudinal cohort study included 98 first-ever stroke patients (67 ± 9 years, 56% female) within one month from the onset who could not ambulate independently. Functional outcome indicators, including toe grip strength, hand grip strength, knee extensor strength, Fugl-Meyer Assessment of Lower Extremity (FMA_LE), and the Postural Assessment Scale for Stroke (PASS), were assessed before and three months after the intervention. We analyzed the correlation between participants' gait function using a 10-meter walk test time and various functional indicators. Then, multiple linear regression analysis was used to investigate whether toe grip strength was related to the improvement of gait function. Correlation analysis revealed a significant positive correlation between the 10MWT time and toe grip strength ratio (affected/unaffected side), with a moderate effect size (r = -0.61, p <0.001). Multiple regression analysis with covariates showed a significant relationship between 10MWT time and toe grip strength ratio (ß = -0.113, p < 0.001), FMA_LE (ß = -1.315, p = 0.004), PASS (ß = -3.275, p <0.001), and age (ß = -0.159, p = 0.004). In conclusion, toe grip strength was an essential factor associated with ambulatory function improvement in subacute stroke patients three months after onset. Additional toe grip muscle strengthening rehabilitation treatment can be expected to help improve the ambulatory function of subacute stroke patients in the future.
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We developed an end-effector-type rehabilitation robot that can uses electro- and permanent magnets to generate a three-way magnetic field to assist hand movements and perform rehabilitation therapy. This study aimed to investigate the therapeutic effect of a rehabilitation program using a three-dimensional (3D) magnetic force-based hand rehabilitation robot on the motor function recovery of the paralyzed hands of patients with stroke. This was a double-blind randomized controlled trial in which 36 patients with subacute stroke were assigned to intervention and control groups of 18 patients each. The intervention group received 30 min of rehabilitation therapy per day for a month using a 3D magnetic force-driven hand rehabilitation robot, whereas the control group received 30 min of conventional occupational therapy to restore upper-limb function. The patients underwent three behavioral assessments at three time points: before starting treatment (T0), after 1 month of treatment (T1), and at the follow-up 1-month after treatment completion (T2). The primary outcome measure was the Wolf Motor Function Test (WMFT), and secondary outcome measures included the Fugl-Meyer Assessment of the Upper Limb (FMA_U), Modified Barthel Index (MBI), and European Quality of Life Five Dimensions (EQ-5D) questionnaire. No participant safety issues were reported during the intervention. Analysis using repeated measures analysis of variance showed significant interaction effects between time and group for both the WMFT score (p = 0.012) and time (p = 0.010). In post hoc analysis, the WMFT scores and time improved significantly more in the patients who received robotic rehabilitation at T1 than in the controls (p = 0.018 and p = 0.012). At T2, we also consistently found improvements in both the WMFT scores and times for the intervention group that were superior to those in the control group (p = 0.024 and p = 0.018, respectively). Similar results were observed for FMA_U, MBI, and EQ-5D. Rehabilitation using the 3D hand-rehabilitation robot effectively restored hand function in the patients with subacute stroke, contributing to improvement in daily independence and quality of life.
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Hydrogels are used in wound dressings because of their tissue-like softness and biocompatibility. However, the clinical translation of hydrogels remains challenging because of their long-term stability, water swellability, and poor tissue adhesiveness. Here, tannic acid (TA) is introduced into a double network (DN) hydrogel consisting of poly(vinyl alcohol) (PVA) and poly(acrylic acid) (PAA) to realize a tough, self-healable, nonswellable, conformally tissue-adhesive, hemostatic, and antibacterial hydrogel. The TA within the DN hydrogel forms a dynamic network, enabling rapid self-healing (within 5 min) and offering effective energy dissipation for toughness and viscoelasticity. Furthermore, the hydrophobic moieties of TA provide a water-shielding effect, rendering the hydrogel nonswellable. A simple chemical modification to the hydrogel further strengthens its interfacial adhesion with tissues (shear strength of ≈31 kPa). Interestingly, the TA also can serve as an effective hemostatic (blood-clotting index of 58.40 ± 1.5) and antibacterial component, which are required for a successful wound dressing. The antibacterial effects of the hydrogel are tested against Escherichia coli and Staphylococcus aureus. Finally, the hydrogel is prepared in patch form and applied to a mouse model to test in vivo biocompatibility and hemostatic performances.
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Hemostáticos , Ratones , Animales , Hemostáticos/farmacología , Hemostáticos/química , Cicatrización de Heridas , Hidrogeles/química , Antibacterianos/farmacología , Antibacterianos/química , AguaRESUMEN
Hydrogels have the potential to play a crucial role in bioelectronics, as they share many properties with human tissues. However, to effectively bridge the gap between electronics and biological systems, hydrogels must possess multiple functionalities, including toughness, stretchability, self-healing ability, three-dimensional (3D) printability, and electrical conductivity. Fabricating such tough and self-healing materials has been reported, but it still remains a challenge to fulfill all of those features, and in particular, 3D printing of hydrogel is in the early stage of the research. In this paper, we present a 3D printable, tough, and self-healing multi-functional hydrogel in one platform made from a blend of poly(vinyl alcohol) (PVA), tannic acid (TA), and poly(acrylic acid) (PAA) hydrogel ink (PVA/TA/PAA hydrogel ink). Based on a reversible hydrogen-bond (H-bond)-based double network, the developed 3D printable hydrogel ink showed excellent printability via shear-thinning behavior, allowing high printing resolution (~100 µm) and successful fabrication of 3D-printed structure by layer-by-layer printing. Moreover, the PVA/TA/PAA hydrogel ink exhibited high toughness (tensile loading of up to ~45.6 kPa), stretchability (elongation of approximately 650%), tissue-like Young's modulus (~15 kPa), and self-healing ability within 5 min. Furthermore, carbon nanotube (CNT) fillers were successfully added to enhance the electrical conductivity of the hydrogel. We confirmed the practicality of the hydrogel inks for bioelectronics by demonstrating biocompatibility, tissue adhesiveness, and strain sensing ability through PVA/TA/PAA/CNT hydrogel ink.
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Clinically, flatfoot, known as pes planus, is quite prevalent. It is classified into 2 types: flexible and rigid, both of which may or may not have symptoms. If a flexible flatfoot is symptomatic, it must be treated to prevent subsequent complications. In principle, most physicians initially use conservative methods, such as foot insoles. This study aimed to demonstrate the effect of long term use of a foot insole using plain radiography as an objective measurement in children with symptomatic flexible flatfoot (SFFF) in large samples. This study analyzed the medical records of 292 children aged < 18 years who were diagnosed with SFFF. Of these, 200 children (62 boys and 138 girls, mean age: 6.49 ± 2.96 years) were selected and conservatively treated with foot insoles. They were periodically followed up within 3 to 4 months to modify the foot insole and perform radiologic evaluations, such as foot radiography. The calcaneal pitch angle (CPA) and talo first metatarsal angle were measured and compared individually using foot lateral radiographs, which were pictured in a bilateral barefoot state. The treatment was terminated by repeating the same procedure until the symptoms disappeared. A significant improvement (P < .001) was observed in the radiological indicators, both CPA and talo first metatarsal angle, regardless of age, after the application of soft foot insoles. However, the right foot CPA in the group with valgus deformity was an exception (P = .078). This study showed that in children diagnosed with SFFF under 18 years of age, wearing a periodically revised foot insole as conservative treatment could not only decrease the symptoms, but also improve the radiologic indices.
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Calcáneo , Pie Plano , Masculino , Femenino , Humanos , Niño , Adolescente , Preescolar , Pie Plano/diagnóstico , Pie , Extremidad Inferior , RadiografíaRESUMEN
Developing bioelectronics that retains their long-term functionalities in the human body during daily activities is a current critical issue. To accomplish this, robust tissue adaptability and biointerfacing of bioelectronics should be achieved. Hydrogels have emerged as promising materials for bioelectronics that can softly adapt to and interface with tissues. However, hydrogels lack toughness, requisite electrical properties, and fabrication methodologies. Additionally, the water-swellable property of hydrogels weakens their mechanical properties. In this work, an intrinsically nonswellable multifunctional hydrogel exhibiting tissue-like moduli ranging from 10 to 100 kPa, toughness (400-873 J m-3 ), stretchability (≈1000% strain), and rapid self-healing ability (within 5 min), is developed. The incorporation of carboxyl- and hydroxyl-functionalized carbon nanotubes (fCNTs) ensures high conductivity of the hydrogel (≈40 S m-1 ), which can be maintained and recovered even after stretching or rupture. After a simple chemical modification, the hydrogel shows tissue-adhesive properties (≈50 kPa) against the target tissues. Moreover, the hydrogel can be 3D printed with a high resolution (≈100 µm) through heat treatment owing to its shear-thinning capacity, endowing it with fabrication versatility. The hydrogel is successfully applied to underwater electromyography (EMG) detection and ex vivo bladder expansion monitoring, demonstrating its potential for practical bioelectronics.
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Hidrogeles , Nanotubos de Carbono , Humanos , Hidrogeles/química , Nanotubos de Carbono/química , Conductividad EléctricaRESUMEN
Stroke patients undergo extensive changes in muscle mass which lead to stroke-related sarcopenia. Stroke-related sarcopenia has a significant impact on the functional outcome of stroke survivors. So, it is important to measure muscle mass in stroke patients. This study aimed to examine the correlation between ultrasonographic quadriceps muscle thickness (QMT) and dual-energy X-ray absorptiometry (DXA) derived appendicular lean mass (ALM) in patients with acute hemiplegic stroke. Twenty five participants were included (13 men and 12 women) in this study, who were diagnosed with stroke within 1 month. For both paretic and non-paretic legs, QMT was measured by an ultrasound and ALM was obtained by performing DXA scan. We analyzed the difference and the correlation between ultrasonographic QMT and DXA-derived lean body mass of both paretic and non-paretic legs. Stroke patients were divided into 2 groups according to the paretic knee extensor power. Ultrasonographic QMT, DXA scan findings, and functional parameters were compared. There was a significant correlation between QMT and ALM index, and between QMT and site-specific lean mass (SSLM) of both the legs for both the sexes (P < .05). In multivariate linear regression model, we made adjustments for the confounding factors of age, sex, body mass index (BMI) and paretic knee extensor power. We observed a positive relationship between QMT and ALM index (P < .05), and between QMT and SSLM of both the legs (P < .05). The % QMT showed higher difference than % SSLM between paretic and non-paretic legs (10.25% vs 4.58%). The QMT measurements of ultrasound show a great relationship with DXA scan findings. Ultrasound better reflects the change of muscle mass between paretic and non-paretic legs than DXA scan at an acute phase of stroke. Ultrasound could be a useful tool to evaluate stroke-related sarcopenia.
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Sarcopenia , Accidente Cerebrovascular , Femenino , Humanos , Masculino , Músculo Esquelético/diagnóstico por imagen , Proyectos Piloto , Estudios Retrospectivos , Sarcopenia/diagnóstico por imagen , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/diagnóstico por imagenRESUMEN
Aging affects salivary gland function and alters saliva production and excretion. This study aimed to investigate whether ascorbic acid can be used to treat salivary gland dysfunction in an extensive aging mouse model of SAMP1/Klotho-/- mice. In our previous study, we found that ascorbic acid biosynthesis was disrupted in the salivary glands of SAMP1/Klotho (-/-) mice subjected to metabolomic profiling analysis. In SAMP1/Klotho -/- mice, daily supplementation with ascorbic acid (100 mg/kg for 18 days) significantly increased saliva secretion compared with the control. The expression of salivary gland functional markers (α-amylase, ZO-1, and Aqua5) is upregulated. Additionally, acetylcholine and/or beta-adrenergic receptors (M1AchR, M3AchR, and Adrb1) were increased by ascorbic acid in the salivary glands of aging mice, and treatment with ascorbic acid upregulated the expression of acetylcholine receptors through the DNA demethylation protein TET2. These results suggest that ascorbic acid could overcome the lack caused by dysfunction of ascorbic acid biosynthesis and induce the recovery of salivary gland function.
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Acetilcolina , Dioxigenasas , Envejecimiento/fisiología , Animales , Ácido Ascórbico/metabolismo , Ácido Ascórbico/farmacología , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Dioxigenasas/metabolismo , Proteínas Klotho/metabolismo , Proteínas de la Membrana/metabolismo , Ratones , Proteínas Nucleares/metabolismo , Receptores Colinérgicos/metabolismo , Glándulas Salivales/fisiologíaRESUMEN
Considering the high metastatic potential of colorectal cancer (CRC), the inhibition of metastasis is important for anti-CRC therapy. Agrimonia pilosa Ledeb (A. pilosa) is a perennial herbaceous plant that is widely distributed in Asia. The extracts of A. pilosa have shown diverse pharmacological properties, such as antimicrobial, anti-inflammatory, and antitumor activities. In the present study, the antimetastatic activity of A. pilosa was evaluated. Methanol extraction from the roots of A. pilosa was performed by high-performance liquid chromatography (HPLC) and 12 fractions were obtained. Among these, fraction 4 showed the most potent inhibitory effect on the migration of colon cancer cells. Using LC-HR MS analysis, quercetin and quercitrin were identified as flavonoids contained in fraction 4. Like fraction 4, quercetin and quercitrin effectively inhibited the migration and invasion of RKO cells. While the level of E-cadherin was increased, the levels of N-cadherin and vimentin were decreased by the same agents. Although they all activate the p38, JNK, and ERK signaling pathways, only SP600125, an inhibitor of the JNK pathway, specifically inhibited the effect of fraction 4, quercetin, and quercitrin on cell migration. An in vivo experiment also confirmed the antitumor activity of quercetin and quercitrin. Collectively, these results suggest that A. pilosa and its two flavonoids, quercetin and quercitrin, are candidates for the antimetastatic treatment of CRC.
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OBJECTIVE: To investigate the association between vitamin E and handgrip strength (HGS) with multiple factors. METHODS: A total of 1,814 participants were included (822 men and 981 women) from the Korean subjects of the 7th Korea National Health and Nutrition Examination Survey in 2018. Data were analyzed using multiple logistic regression to determine the correlation between vitamin E and HGS with potential confounding factors. RESULTS: In the multiple logistic regression model, only the young age group (19-40 years) of men showed a positive relationship between vitamin E and HGS. However, in older age groups (41-80 years) of men and all age groups of women, there was no statistically significant result. After adjusting for confounding factors, young men showed higher vitamin E levels and higher HGS. Conversely, women and older age groups did not show significant results after adjusting for confounding factors. CONCLUSION: In this study, the serum vitamin E level had a positive effect on HGS in young men (<40 years). Further research is needed on this topic regarding vitamin E intake and other objective measures.
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Skin aging occurs inevitably as a natural result of physiological changes over time. In particular, solar exposure of the skin accounts for up to 90% of skin damage. Numerous studies have examined the ability of dietary constituents to prevent skin aging, and recent research has emphasized the role of functional probiotics in intestinal function and skin aging. However, the mechanism of the interactions between aging and probiotics has not been elucidated yet. The aim of this study was to determine the role of exopolysaccharides (EPS) produced by lactic acid bacteria (LAB) identified as Lactobacillus plantarum HY7714 in regulating tight junctions in intestinal epithelial cells and increasing moisture retention in human dermal fibroblasts cells. We observed that HY7714 EPS controlled intestinal tight junctions in Caco-2 cells by upregulating the genes encoding occludin-1 (OCL-1) and zonula occluden-1 (ZO-1). In addition, HY7714 EPS effectively improved UVB-induced cytotoxicity and hydration capacity in HS68 cells by downregulating production of metalloproteinases (MMPs) and reactive oxygen species (ROS). In summary, HY7714 EPS is an effective anti-aging molecule in skin and may have therapeutic potential against skin diseases and UVB-induced damage. Therefore, HY7714 EPS serves as a functional substance in skin-gut axis communication.
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Tracto Gastrointestinal/efectos de los fármacos , Lactobacillus plantarum/metabolismo , Polisacáridos/farmacología , Sustancias Protectoras/farmacología , Envejecimiento de la Piel/efectos de los fármacos , Piel/efectos de los fármacos , Células CACO-2 , Línea Celular Tumoral , Células Cultivadas , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Microbioma Gastrointestinal , Tracto Gastrointestinal/microbiología , Humanos , Ocludina/metabolismo , Probióticos/metabolismo , Piel/metabolismo , Uniones Estrechas/efectos de los fármacos , Uniones Estrechas/metabolismoRESUMEN
Salivary gland dysfunction induces salivary flow reduction and a dry mouth, and commonly involves oral dysfunction, tooth structure deterioration, and infection through reduced salivation. This study aimed to investigate the impact of aging on the salivary gland by a metabolomics approach in an extensive aging mouse model, SAMP1/Klotho -/- mice. We found that the salivary secretion of SAMP1/Klotho -/- mice was dramatically decreased compared with that of SAMP1/Klotho WT (+/+) mice. Metabolomics profiling analysis showed that the level of acetylcholine was significantly decreased in SAMP1/Klotho -/- mice, although the corresponding levels of acetylcholine precursors, acetyl-CoA and choline, increased. Interestingly, the mRNA and protein expression of choline acetyltransferase (ChAT), which is responsible for catalyzing acetylcholine synthesis, was significantly decreased in SAMP1/Klotho -/- mice. The overexpression of ChAT induced the expression of salivary gland functional markers (α-amylase, ZO-1, and Aqua5) in primary cultured salivary gland cells from SAMP1/Klotho +/+ and -/- mice. In an in vivo study, adeno-associated virus (AAV)-ChAT transduction significantly increased saliva secretion compared with the control in SAMP1/Klotho -/- mice. These results suggest that the dysfunction in acetylcholine biosynthesis induced by ChAT reduction may cause impaired salivary gland function.
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Acetilcolina/metabolismo , Envejecimiento/metabolismo , Colina O-Acetiltransferasa/metabolismo , Glucuronidasa/metabolismo , Proteínas de la Membrana/metabolismo , Proteínas Nucleares/metabolismo , Glándulas Salivales/metabolismo , Acetilcoenzima A/metabolismo , Acetilcolina/genética , Envejecimiento/genética , Animales , Línea Celular , Colina/metabolismo , Colina O-Acetiltransferasa/genética , Regulación hacia Abajo , Regulación de la Expresión Génica/genética , Técnicas de Silenciamiento del Gen , Glucuronidasa/genética , Humanos , Proteínas Klotho , Proteínas de la Membrana/genética , Metabolómica , Ratones , Ratones Noqueados , Proteínas Nucleares/genética , Glándulas Salivales/enzimología , Regulación hacia Arriba , Proteína de la Zonula Occludens-1/genética , Proteína de la Zonula Occludens-1/metabolismo , alfa-Amilasas/genética , alfa-Amilasas/metabolismoRESUMEN
Homeobox C6 (HOXC6) is a transcription factor that plays a role in the malignant progression of various cancers. However, the roles of HOXC6 and its regulatory mechanism remain unclear. In this study, we used microRNA (miRNA) regulatory networks to identify key regulatory interactions responsible for HOXC6-mediated cancer progression. In microarray profiling of miRNAs, the levels of miRNAs such as hsa-miR-188-5p, hsa-miR-8063, and hsa-miR-8064 were significantly increased in HOXC6-overexpressing cells. Higher positive expression rates of HOXC6 and miR-188-5p were observed in malignant cancer. We also found that HOXC6 significantly upregulated miR-188-5p expression. The underlying function of HOXC6-mediated miR-188-5p expression was predicted through TargetScan and the MiRNA Database. Overexpression of mir-188-5p inhibited the expression of forkhead box N2 (FOXN2), a tumor suppressor gene. Furthermore, in the luciferase assay, miR-188-5p bound to the 3'-UTR of FOXN2 and was mainly responsible for the dysregulation of FOXN2 expression. Silencing FOXN2 induced cell migration, and the effect of FOXN2 silencing was enhanced when the HOXC6/miR-188-5p axis was induced. These results suggest that HOXC6/miR-188-5p may induce malignant progression in cancer by inhibiting the activation of the FOXN2 signaling pathway.
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Factores de Transcripción Forkhead/genética , Proteínas de Homeodominio/genética , MicroARNs/genética , Neoplasias de la Boca/genética , Regulación hacia Arriba , Regiones no Traducidas 3' , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Células HEK293 , Humanos , Análisis de Secuencia por Matrices de OligonucleótidosRESUMEN
OBJECTIVE: To compare the relationship of the Bayley Scales of Infant and Toddler Development 3rd Edition (K-BSID-III) language score and the Sequenced Language Scale for Infant (SELSI) score and evaluate the sensitivity and specificity of K-BSID-III language score and optimal cutoff value with receiver operator characteristic (ROC) curve analysis in infants and toddlers with delayed language development. METHODS: A total of 104 children with suspected language developmental delay were included in this retrospective study. Subjects were tested using the K-BSID-III and SELSI and subdivided into several groups according to the severity of language scores. ROC curve analysis was performed to assess K-BSID-III for delayed language development. RESULTS: Receptive and expressive language subscales of the K-BSID-III showed markedly significant correlation with the SELSI scores (p<0.001). ROC analysis showed an area under the curve of 0.877 (p<0.001) in SELSI receptive score and 0.935 (p<0.001) in SELSI expressive score. The optimal cutoff value where sensitivity of 85% and specificity of 81% were achieved with the K-BSID-III receptive score was 1.50 (between average and low average) in the SELSI receptive score. The optimal cutoff value where sensitivity of 96% and specificity of 82% were achieved with the K-BSID-III expressive score was also 1.50 in the SELSI expressive score. CONCLUSION: In this study, the correlations between K-BSID-III and SELSI language scores were statistically significant. However, the interpretation should be considered carefully in low average group due to tendency of underestimation of delayed language development.
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Oxidative stress and inflammation play critical roles in the development of cardiovascular diseases. Cinnamaldehyde (CA) is a natural compound from Cinnamomum cassia, and its anticancer, antimicrobial and antiinflammatory activities have been widely investigated. In the present study, the cytoprotective and antiinflammatory effects of CA on H2O2 or tumor necrosis factor (TNF)αexposed human umbilical vein endothelial cells (HUVECs) were examined. CA and its natural derivative, 2methoxycinnamaldehyde (MCA), markedly increased the cellular protein level of heme oxygenase1 (HO1) and promoted the translocation of nuclear factor erythroid 2related factor 2 (Nrf2) to the nucleus. CAmediated Nrf2/HO1 activation protected the HUVECs from H2O2induced oxidative stress, which promotes apoptosis. HO1 depletion by siRNA attenuated the CAmediated cell protective effects against oxidative stress. Additionally, CA markedly inhibited the adhesion of U937 monocytic cells to HUVECs by decreasing the expression level of vascular cell adhesion protein 1 (VCAM1). An in vivo experiment confirmed the antiinflammatory effects of CA, as lipopolysaccharide (LPS)induced inflammatory cell infiltration was effectively inhibited by the compound. Overall, these observations suggest that CA may be used as a therapeutic agent for oxidative stressmediated cardiovascular diseases, such as atherosclerosis.
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Acroleína/análogos & derivados , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Factor de Necrosis Tumoral alfa/farmacología , Acroleína/farmacología , Animales , Western Blotting , Hemo-Oxigenasa 1/metabolismo , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Humanos , Inflamación/metabolismo , Ratones , Factor 2 Relacionado con NF-E2/metabolismo , Estrés Oxidativo/efectos de los fármacos , Células U937 , Molécula 1 de Adhesión Celular Vascular/metabolismoRESUMEN
Despite increasing research on the gut-skin axis, there is a lack of comprehensive studies on the improvement of skin health through the regulation of the intestinal condition in humans. In this study, we investigated the benefits of Lactobacillus plantarum HY7714 (HY7714) consumption on skin health through its modulatory effects on the intestine and ensuing immune responses. HY7714 consumption led to differences in bacterial abundances from phylum to genus level, including increases in Actinobacteria followed by Bifidobacterium and a decrease in Proteobacteria. Additionally, HY7714 significantly ameliorated inflammation by reducing matrix metallopeptidases (MMP-2 and MMP-9), zonulin, and calprotectin in plasma, all of which are related to skin and intestinal permeability. Furthermore, RNA-seq analysis revealed its efficacy at restoring the integrity of the gut barrier by regulating gene expression associated with the extracellular matrix and immunity. This was evident by the upregulation of IGFBP5, SERPINE1, EFEMP1, COL6A3, and SEMA3B and downregulation of MT2A, MT1E, MT1X, MT1G, and MT1F between TNF- α and TNF- α plus HY7714 treated Caco-2 cells. These results propose the potential mechanistic role of HY7714 on skin health by the regulation of the gut condition.