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1.
Ophthalmol Retina ; 5(11): 1096, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34752303
2.
Biochem Biophys Res Commun ; 586: 157-162, 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34847441

RESUMO

Sarcopenia is the age-related loss of muscle mass and function and no pharmacological medication has been approved for its treatment. We established an atrogin-1/MAFbx promoter assay to find drug candidates that inhibit myotube atrophy. Alverine citrate (AC) was identified using high-throughput screening of an existing drug library. AC is an established medicine for stomach and intestinal spasms. AC treatment increased myotube diameter and inhibited atrophy signals induced by either C26-conditioned medium or dexamethasone in cultured C2C12 myoblasts. AC also enhanced myoblast fusion through the upregulation of fusion-related genes during C2C12 myoblast differentiation. Oral administration of AC improves muscle mass and physical performance in aged mice, as well as hindlimb-disused mice. Taken together, our data suggest that AC may be a novel therapeutic candidate for improving muscle weakness, including sarcopenia.

3.
ACS Appl Mater Interfaces ; 13(41): 49128-49136, 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34597029

RESUMO

Hybrid materials comprising graphene and palladium nanoparticles (PdNPs) are desirable for high-performance hydrogen detection because of the high specific surface area, electron mobility, and flexibility of graphene and the high electrochemical responsivity and reversibility of PdNPs. However, obtaining hybrid materials is energy-intensive and time-consuming. Here, a facile and rapid laser photothermochemical single-step processing method to synchronously produce a nanoassembly of three-dimensional porous graphene and PdNPs from polymer films is reported. Polymers with intrinsic microporosity show high solubility in volatile solvents and miscibility with inorganic materials, allowing the fabrication of homogeneous polymer films containing Pd ligands. The films are photothermally processed using a laser to generate a nanohybrid via photoinduced thermal and chemical processes. The nanohybrid exhibits four-times-enhanced electrical conductivity compared to plain porous graphene, high crystallinity, and coherent covalent metal bonds with a homogeneous size and distribution of PdNPs in hierarchical micro/meso/macroporous graphene structures, allowing high-performance hydrogen sensing (1 ppm) with outstanding mechanical reliability, flexibility, and durability upon bending and twisting. The nanoassembly is integrated with a wireless sensing platform, and hydrogen leakage (1 ppm) is detected using a smart phone. This laser-based nanomanufacturing of the nanoassembly can potentially be applied to wearable detector production platforms in the military and industry.

4.
Exp Eye Res ; 212: 108788, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34637791

RESUMO

This study aimed to investigate the efficacy of intravitreal povidone-iodine (PI) administration for the treatment of Candida albicans endophthalmitis. Forty New Zealand white rabbits were divided into four groups (n = 10 per group). After the induction of endophthalmitis using Candida albicans, groups A, B, and C received single intravitreal injections of 0.035 mg voriconazole, 0.3 mg PI, and their combination, respectively. Rabbits that were administered sham injections were in group D as controls. Fundus photography, vitreous culture, electroretinography (ERG), and histologic examinations of the retina were conducted on day 7. The anterior chamber flare (grade 0 to 4), severity of iritis (grade 0 to 4), and vitreous opacity (grade 0 to 3) were scored. Candida albicans was cultured in the vitreous sample. On day 7, the vitreous opacities were found in all groups. Compared to that in group D, groups A, B, and C showed a lower score for flare (p < 0.001) and iritis (p < 0.001) and less fungal growth in the vitreous culture (n = 2, 1, 1, and 10 in groups A, B, C, and D, respectively; p < 0.001). Furthermore, ERG and histologic findings demonstrated less affected a- and b-waves and damaged retinal tissues in groups A, B, and C. However, these findings were not different among groups A, B, and C. PI significantly improved Candida albicans endophthalmitis, and the effect was comparable that of the voriconazole, although some vitreous opacities remained. No synergistic effect of the combination of PI and voriconazole was observed. Intravitreal PI may be useful to treat Candida albicans endophthalmitis.

5.
Aging (Albany NY) ; 13(17): 21009-21028, 2021 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-34492635

RESUMO

The ability to maintain systemic metabolic homeostasis through various mechanisms represents a crucial strength of kidneys in the study of metabolic syndrome or aging. Moreover, age-associated kidney failure has been widely accepted. However, efforts to demonstrate aging-dependent renal metabolic rewiring have been limited. In the present study, we investigated aging-related renal metabolic determinants by integrating metabolomic and transcriptomic data sets from kidneys of young (3 months, n = 7 and 3 for respectively) and old (24 months, n = 8 and 3 for respectively) naive C57BL/6 male mice. Metabolite profiling analysis was conducted, followed by data processing via network and pathway analyses, to identify differential metabolites. In the aged group, the levels of glutathione and oxidized glutathione were significantly increased, but the levels of gamma-glutamyl amino acids, amino acids combined with the gamma-glutamyl moiety from glutathione by membrane transpeptidases, and circulating glutathione levels were decreased. In transcriptomic analysis, differential expression of metabolic enzymes is consistent with the hypothesis of aging-dependent rewiring in renal glutathione metabolism; pathway and network analyses further revealed the increased expression of immune-related genes in the aged group. Collectively, our integrative analysis results revealed that defective renal glutathione metabolism is a signature of renal aging. Therefore, we hypothesize that restraining renal glutathione metabolism might alleviate or delay age-associated renal metabolic deterioration, and aberrant activation of the renal immune system.

6.
Int J Mol Sci ; 22(17)2021 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-34502333

RESUMO

Plants produce a wide variety of natural volatile organic compounds (NVOCs), many of which are unique to each species. These compounds serve many purposes, such as fending off herbivores and adapting to changes in temperature and water supply. Interestingly, although NVOCs are synthesized to deter herbivores, many of these compounds have been found to possess several therapeutic qualities, such as promoting nerve stability, enhancing sleep, and suppressing hyperresponsiveness, in addition to acting as antioxidants and anti-inflammatory agents. Therefore, many NVOCs are promising drug candidates for disease treatment and prevention. Given their volatile nature, these compounds can be administered to patients through inhalation, which is often more comfortable and convenient than other administration routes. However, the development of NVOC-based drug candidates requires a careful evaluation of the molecular mechanisms that drive their therapeutic properties to avoid potential adverse effects. Furthermore, even compounds that appear generally safe might have toxic effects depending on their dose, and therefore their toxicological assessment is also critical. In order to enhance the usage of NVOCs this short review focuses not only on the biological activities and therapeutic mode of action of representative NVOCs but also their toxic effects.


Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Inflamação/tratamento farmacológico , Compostos Orgânicos Voláteis/farmacologia , Animais , Humanos
7.
Nutrients ; 13(9)2021 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-34578808

RESUMO

The aim of this study was to re-validate the changes in natural killer (NK) cell cytotoxicity and cytokines related to T cells after Sil-Q1 (SQ; silk peptide) supplementation in a larger pool of Korean adults with minimized daily dose of SQ and controlling seasonal influence compared to the previous study. A total of 130 subjects were randomly assigned (1:1) to consume either 7.5 g of SQ or placebo for 8 weeks. NK cell cytotoxicity and cytokines were measured at T0 (baseline) and T8 (follow-up). Comparing the NK cell cytotoxicity values at T0 and T8 within each group, the cytotoxicity at all effector cell (E) to target cell (T) ratios of 10:1, 5:1, 2.5:1, and 1.25:1 was significantly increased in the SQ group at T8. Additionally, significant differences in the changed value (Δ, subtract baseline values from follow-up values) comparison between the groups at E:T = 10:1, 5:1, and 2.5:1 were found. As a secondary endpoint, the interleukin (IL)-12 level in the SQ group was significantly increased for 8 weeks, and Δ IL-12 in the SQ group was greater than in the placebo group. In conclusion, the present study showed considerable practical implications of SQ supplementation. Thus, SQ is an effective and safe functional food supplement for enhancing immune function.


Assuntos
Aminoácidos/administração & dosagem , Citocinas/efeitos dos fármacos , Células Matadoras Naturais/efeitos dos fármacos , Peptídeos/administração & dosagem , Seda/administração & dosagem , Citocinas/imunologia , Suplementos Nutricionais , Feminino , Alimento Funcional , Humanos , Interleucina-12/sangue , Células Matadoras Naturais/imunologia , Coreia (Geográfico) , Masculino , Pessoa de Meia-Idade , Estações do Ano , Seda/química , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Resultado do Tratamento
8.
Exp Mol Med ; 53(7): 1192-1204, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34316018

RESUMO

Loss-of-function variant in the gene encoding the KCNQ4 potassium channel causes autosomal dominant nonsyndromic hearing loss (DFNA2), and no effective pharmacotherapeutics have been developed to reverse channel activity impairment. Phosphatidylinositol 4,5-bisphosphate (PIP2), an obligatory phospholipid for maintaining KCNQ channel activity, confers differential pharmacological sensitivity of channels to KCNQ openers. Through whole-exome sequencing of DFNA2 families, we identified three novel KCNQ4 variants related to diverse auditory phenotypes in the proximal C-terminus (p.Arg331Gln), the C-terminus of the S6 segment (p.Gly319Asp), and the pore region (p.Ala271_Asp272del). Potassium currents in HEK293T cells expressing each KCNQ4 variant were recorded by patch-clamp, and functional recovery by PIP2 expression or KCNQ openers was examined. In the homomeric expression setting, the three novel KCNQ4 mutant proteins lost conductance and were unresponsive to KCNQ openers or PIP2 expression. Loss of p.Arg331Gln conductance was slightly restored by a tandem concatemer channel (WT-p.R331Q), and increased PIP2 expression further increased the concatemer current to the level of the WT channel. Strikingly, an impaired homomeric p.Gly319Asp channel exhibited hyperactivity when a concatemer (WT-p.G319D), with a negative shift in the voltage dependence of activation. Correspondingly, a KCNQ inhibitor and chelation of PIP2 effectively downregulated the hyperactive WT-p.G319D concatemer channel. Conversely, the pore-region variant (p.Ala271_Asp272del) was nonrescuable under any condition. Collectively, these novel KCNQ4 variants may constitute therapeutic targets that can be manipulated by the PIP2 level and KCNQ-regulating drugs under the physiological context of heterozygous expression. Our research contributes to the establishment of a genotype/mechanism-based therapeutic portfolio for DFNA2.

9.
Appl Microsc ; 51(1): 11, 2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34255203

RESUMO

Spider capture silk is a natural scaffolding material that outperforms most synthetic materials in terms of its combination of strength and elasticity. Among the various kinds of silk threads, cribellar thread is the most primitive prey-capturing type of spider web material. We analyzed the functional organization of the sieve-like cribellum spigots and specialized calamistral comb bristles for capture thread production by the titanoecid spider Nurscia albofasciata. The outer cribellar surface is covered with thousands of tiny spigots, and the cribellar plate produces non-sticky threads composed of thousands of fine nanofibers. N. albofasciata cribellar spigots are typically about 10 µm long, and each spigot appears as a long individual shaft with a pagoda-like tiered tip. The five distinct segments comprising each spigot is a defining characteristic of this spider. This segmented and flexible structure not only allows for spigots to bend individually and join with adjacent spigots, but it also enables spigots to draw the silk fibrils from their cribella with rows of calamistral leg bristles to form cribellar prey-capture threads.

10.
Sci Rep ; 11(1): 14339, 2021 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-34253829

RESUMO

Although many prediction models for cardiovascular diseases (CVDs) have been developed and validated for Western populations, the development of CVD prediction models for Asians has been slow. Our cohort study retrospectively analyzed the incidence of CVD that occurred between January 1, 2009, and December 31, 2016, in all Koreans who underwent national health screening. This dataset included 21,581,796 adults between the ages of 40 and 79 years (10,412,947 men, 11,168,849 women) without CVD at baseline. The primary outcome, CVD, was defined as the development of any of the following: acute coronary syndrome, cerebral infarction, and cerebral hemorrhage, as defined with health insurance claims data. The prediction model was constructed by Cox proportional hazard regression and validated with tenfold cross-validation. The performance of the models was evaluated through Harrell's C-index and Brier score. The discrimination of the models was assessed by the area under the receiver operating characteristic curve (AUROC). Our model showed an AUROC of 0.762 in men and 0.811 in women. The Brier score of our model was 0.018 in men and 0.010 in women, which was better than the pooled cohort equation (PCE). Our novel model performed better than the FRS and PCE for Koreans.


Assuntos
Doenças Cardiovasculares/epidemiologia , Adulto , Estudos de Coortes , Humanos , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Curva ROC , República da Coreia/epidemiologia , Estudos Retrospectivos
11.
Nat Mater ; 20(11): 1559-1570, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34326506

RESUMO

Flexible electronic/optoelectronic systems that can intimately integrate onto the surfaces of vital organ systems have the potential to offer revolutionary diagnostic and therapeutic capabilities relevant to a wide spectrum of diseases and disorders. The critical interfaces between such technologies and living tissues must provide soft mechanical coupling and efficient optical/electrical/chemical exchange. Here, we introduce a functional adhesive bioelectronic-tissue interface material, in the forms of mechanically compliant, electrically conductive, and optically transparent encapsulating coatings, interfacial layers or supporting matrices. These materials strongly bond both to the surfaces of the devices and to those of different internal organs, with stable adhesion for several days to months, in chemistries that can be tailored to bioresorb at controlled rates. Experimental demonstrations in live animal models include device applications that range from battery-free optoelectronic systems for deep-brain optogenetics and subdermal phototherapy to wireless millimetre-scale pacemakers and flexible multielectrode epicardial arrays. These advances have immediate applicability across nearly all types of bioelectronic/optoelectronic system currently used in animal model studies, and they also have the potential for future treatment of life-threatening diseases and disorders in humans.

12.
Korean J Ophthalmol ; 35(3): 207-214, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34120419

RESUMO

PURPOSE: To describe the development of multiple retinal hemorrhages after uncomplicated macular hole (MH) surgery, and to determine the associated factors. METHODS: The medical records of 163 patients (167 eyes) diagnosed with idiopathic MHs and who underwent surgery at Pusan National University Hospital between March 2016 and July 2018 were retrospectively reviewed. The development of retinal hemorrhages was evaluated using ultra-widefield fundus photographs. Multiple retinal hemorrhages were defined as three or more dot or blot hemorrhages that had not been observed before and during the surgery. The patients were divided into two groups according to the presence of multiple retinal hemorrhages. The variable parameters were compared between the two groups to find the risk factors. The associated factors were evaluated further for the independent factor using multiple logistic regression analysis. RESULTS: Multiple retinal hemorrhages were observed in 31 eyes (18.6%) after MH surgery. The associated factors were the surgical induction of posterior vitreous detachment (PVD) (p = 0.003), use of the internal limiting membrane flap technique (p = 0.028), and staining with Brilliant Blue G (BBG) (p = 0.003). Retinal hemorrhages were exclusively observed in eyes in which BBG was used. Surgical PVD induction was the only independent risk factor (odds ratio, 13.099; p = 0.013). No statistically significant differences were observed between the two groups in the postoperative visual outcomes and MH closure rate. Additionally, patients who underwent surgery for idiopathic epiretinal membrane during the study period were reviewed to validate the above findings. Multiple retinal hemorrhages were noted in only one case (0.4%) in which BBG was used after surgical induction of PVD. CONCLUSIONS: Multiple retinal hemorrhages after MH surgery appear to be related to the intravitreal use of BBG in eyes that sustained mechanical damage because of surgical induction of PVD; however, they did not affect surgical outcomes.


Assuntos
Perfurações Retinianas , Humanos , Hemorragia Retiniana/diagnóstico , Hemorragia Retiniana/epidemiologia , Hemorragia Retiniana/etiologia , Perfurações Retinianas/diagnóstico , Perfurações Retinianas/cirurgia , Estudos Retrospectivos , Corantes de Rosanilina , Tomografia de Coerência Óptica , Acuidade Visual , Vitrectomia
13.
Nat Biotechnol ; 39(10): 1228-1238, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34183859

RESUMO

Temporary cardiac pacemakers used in periods of need during surgical recovery involve percutaneous leads and externalized hardware that carry risks of infection, constrain patient mobility and may damage the heart during lead removal. Here we report a leadless, battery-free, fully implantable cardiac pacemaker for postoperative control of cardiac rate and rhythm that undergoes complete dissolution and clearance by natural biological processes after a defined operating timeframe. We show that these devices provide effective pacing of hearts of various sizes in mouse, rat, rabbit, canine and human cardiac models, with tailored geometries and operation timescales, powered by wireless energy transfer. This approach overcomes key disadvantages of traditional temporary pacing devices and may serve as the basis for the next generation of postoperative temporary pacing technology.


Assuntos
Implantes Absorvíveis , Marca-Passo Artificial , Animais , Bloqueio Atrioventricular/terapia , Modelos Animais de Doenças , Cães , Desenho de Equipamento , Humanos , Camundongos , Coelhos , Ratos , Tecnologia sem Fio
14.
Exp Eye Res ; 208: 108614, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33971221

RESUMO

The aim of this study was to investigate the efficacy of intravitreal povidone-iodine (PI) in the treatment of vancomycin-resistant Enterococcus faecalis (VRE) endophthalmitis. Fifty New Zealand white rabbits were divided into 5 groups (n = 10 in each group). After the induction of endophthalmitis using VRE (minimum inhibitory concentration [MIC] ≥ 40 µg/mL) in the right eye, Group A, B, C, and D received intravitreal injections of 0.1% PI, 0.3% PI, 0.05% vancomycin, and 0.5% vancomycin, respectively. Eyes in Group E were used as controls. Fundus photography, vitreous culture, electroretinography (ERG), and histologic examinations of the retina were conducted on day 14. A marked improvement in endophthalmitis was observed in Group A, B, C and D, compared to Group E. Fundus photographs showed mild vitreous opacities in Group A and B, and moderate vitreous opacity in Group C. All eyes in Group D had a clear vitreous. In vitreous culture, bacterial growth was found in 6 eyes (100, 200, 200, 400, 500, and 500 colony-forming units) in Group C, but not in Groups A, B, or D. ERG and histological examination also indicated intraocular damage in Group C. Our results show that intravitreal injection of PI, even at low concentrations, was effective for treatment of VRE endophthalmitis, although some vitreous opacity remained. Intravitreal vancomycin injection was also useful to treat resistant strains, if used at a higher concentration within the safety threshold.


Assuntos
Endoftalmite/tratamento farmacológico , Enterococcus faecalis/isolamento & purificação , Infecções Oculares Bacterianas/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Povidona-Iodo/administração & dosagem , Resistência a Vancomicina , Animais , Anti-Infecciosos Locais/administração & dosagem , Contagem de Colônia Microbiana , Modelos Animais de Doenças , Eletrorretinografia , Endoftalmite/microbiologia , Endoftalmite/patologia , Infecções Oculares Bacterianas/microbiologia , Infecções Oculares Bacterianas/patologia , Infecções por Bactérias Gram-Positivas/microbiologia , Infecções por Bactérias Gram-Positivas/patologia , Injeções Intravítreas , Coelhos , Retina/patologia , Corpo Vítreo/microbiologia , Corpo Vítreo/patologia
15.
J Med Food ; 24(4): 431-435, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33861936

RESUMO

The anticancer effects of Shinan (Shinan-South Korea) sea salts on azoxymethane (AOM)/dextran sodium sulfate (DSS) with high fat diet (HFD)-induced colon cancer and obesity in C57BL/6N mice were studied. We prepared three types of sea salt: generally manufactured sea salt (GS), generally manufactured after filtering seawater (FS), and manufactured with only new seawater (NS). Sea salt intake increased colon length and reduced colon length/weight ratio, tumor number, and progression of colon cancer in colon tissue. The differently prepared sea salts also ameliorated liver injury. In addition, the mineral composition of each salt was different. Moreover, the sea salts enhanced activation of natural killer cell (CD56) expression in colon and spleen tissues. However, the mineral compositions of sea salts were not simply associated with anticancer effects in AOM/DSS+HFD induced mice. Thus, the anticolorectal cancer effects of sea salts may be mediated by different factors, which remain to be identified.


Assuntos
Colite , Neoplasias do Colo , Neoplasias Colorretais , Animais , Azoximetano/toxicidade , Colo , Neoplasias Colorretais/tratamento farmacológico , Sulfato de Dextrana , Dieta Hiperlipídica/efeitos adversos , Camundongos , Camundongos Endogâmicos C57BL , República da Coreia , Cloreto de Sódio na Dieta
16.
Arch Pharm Res ; 44(4): 378-401, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33837513

RESUMO

The role of advanced glycation end products (AGEs) is not limited to diabetes and diabetes-related complications. There are multiple modulators, including the receptor for advanced glycation end products, high mobility group box 1, glyoxalase 1, nuclear factor-kappa B, tumor necrosis factor-α, chronic unpredictable stress, reactive oxygen species, and inflammatory cytokines, which interact with AGE signaling and control diabetes, modulating these interacting modulators. The progression of diabetes, as well as related complications, can be controlled and treated. Natural products rich in bioactive constituents can interact with AGEs and their related mediators through various signaling cascades, thereby controlling and preventing the progression of diabetes. This review provides a deeper assessment of the signaling pathway, interactions between phytochemicals and AGEs, and its mediators, to develop a multifold therapeutic approach to prevent and treat diabetes and its related complications.


Assuntos
Diabetes Mellitus/tratamento farmacológico , Produtos Finais de Glicação Avançada/antagonistas & inibidores , Hipoglicemiantes/antagonistas & inibidores , Compostos Fitoquímicos/farmacologia , Animais , Produtos Finais de Glicação Avançada/metabolismo , Humanos , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/farmacologia , Compostos Fitoquímicos/química , Transdução de Sinais/efeitos dos fármacos
17.
J Gastroenterol Hepatol ; 36(7): 1997-2007, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33554346

RESUMO

BACKGROUND AND AIM: Stem cell treatments using scaffolds for liver disease have been well studied. However, macro-encapsulation of mesenchymal stem cells (MSCs) to minimize or inhibit stem cell homing has not been evaluated. Here, we conducted a proof-of-concept study using MSCs macro-encapsulated in poly lactic-co-glycolic acid in liver disease models. METHODS: Poly lactic-co-glycolic acid semipermeable membranes (surface pore size up to 40 µm) were used as the macro-encapsulation system. Macro-encapsulated pouches were loaded with MSCs and sealed. Each pouch was implanted in the subcutaneous region of the dorsum or interlobular space of the liver. Acute liver injury was induced using thioacetamide intraperitoneal injection thrice a week. For the chronic liver fibrosis model, thioacetamide dose was gradually increased, starting from 100 to 400 mg/kg over 16 weeks (thrice a week). RESULTS: In the acute liver injury model, the treated groups showed decreased liver inflammation and necrosis compared with the control. Hepatic fibrosis decreased in the treated group in the chronic liver fibrosis model compared with that in the control group. Encapsulated MSCs exhibited changed cell morphology and characteristics after implantation, showing increased periodic acid-Schiff staining and CYP2E1 expression. Migration and homing of MSCs into the liver was not observed. Under hypoxic conditions, macro-encapsulated MSCs secreted more growth hormones, including vascular endothelial growth factor, platelet-derived growth factor, angiopoietin-2, and placental growth factor, than monolayered MSCs in vitro. CONCLUSIONS: Macro-encapsulated MSCs attenuate hepatic inflammation and fibrosis by upregulating hypoxia-induced growth hormone secretion in liver disease models.

18.
Int J Stem Cells ; 14(2): 221-228, 2021 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-33632987

RESUMO

Background and Objectives: Hypoxia is frequently used to enhance stem cell function. However, the optimal level of hypoxia for growth and function of human embryonic stem cell-derived mesenchymal stem cells (hES-MSCs) is yet to be determined. The purpose of this study was to find the optimal level of hypoxia for hES-MSCs and characteristics of hES-MSCs cultured under these optimal hypoxic conditions. Methods and Results: Cell viability and changes in the morphology of hES-MSCs were determined through cell proliferation and CCK-8 assay. The hES-MSCs were preconditioned under various hypoxic conditions (0.5∼5% O2 and 24∼72 h). The expression of cytokines in each culture condition was compared using cytokine array analysis. The morphology of hES-MSCs did not change under various hypoxic culture conditions. hES-MSCs viability after 48 h incubation in 2% O2 condition was higher than that in normoxic condition. HIF1α expression was increased up to six folds after 48 h of hypoxic preconditioning. HIF1α expression in hES-MSCs peaked after 48 h of incubation in 1% O2 condition. The expressions of PDGF-BB, IGFBP-6, VEGF-A, and angiogenin were increased after hES-MSCs were incubated for 48 h in 2% O2 condition. Conclusions: The hES-MSCs viability and expressions of PDGF-BB, IGFBP-6, VEGF-A, and angiogenin increased after 48 h incubation in 2% O2 condition.

20.
Eur Radiol ; 31(3): 1548-1557, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32894357

RESUMO

OBJECTIVES: To evaluate potential of conventional MRI and diffusion-weighted imaging (DWI) for differentiating malignant from benign peripheral nerve sheath tumors (PNSTs). METHODS: Eighty-seven cases of malignant or benign PNSTs in the trunk or extremities that underwent conventional MRI with contrast enhancement, DWI, and pathologic confirmation between Sep. 2014 and Dec. 2017 were identified. Of these, 55 tumors of uncertain nature on MRI were included. Tumor size, signal, and morphology were reviewed on conventional MRI, and apparent diffusion coefficient (ADC) values of solid enhancing portions were measured from DWI. Patient demographics, MRI features, and ADC values were compared between benign and malignant tumors, and robust imaging findings for malignant peripheral nerve sheath tumors (MPNSTs) were identified using multivariable models. RESULTS: A total of 55 uncertain tumors consisted of 18 malignant and 37 benign PNSTs. On MRI, tumor size, margin, perilesional edema, and presence of split fat, fascicular, and target signs were significantly different between groups (p < 0.05), as were mean and minimum ADC values (p = 0.002, p < 0.0001). Most inter-reader agreement was moderate to excellent (κ value, 0.45-1.0). The mean ADC value and absence of a split fat sign were identified as being associated with MPNSTs (odds ratios = 13.19 and 25.67 for reader 1; 49.05 and 117.91 for reader 2, respectively). The C-indices obtained by combining these two findings were 0.90 and 0.95, respectively. CONCLUSIONS: Benign and malignant PNSTs showed different features on MRI and DWI. A combination of mean ADC value and absence of split fat was excellent for discriminating malignant from benign PNSTs. KEY POINTS: • It is important to distinguish between malignant peripheral nerve sheath tumors (MPNSTs) and benign peripheral nerve sheath tumors (BPNSTs) to ensure an appropriate treatment plan. • On conventional MRI and diffusion-weighted imaging (DWI), MPNSTs and BPNSTs showed significant differences in tumor size, margin, presence of perilesional edema, and absence of split fat, fascicular, and target signs. • Absence of a split fat sign and mean apparent diffusion coefficient (ADC) values were robust imaging findings distinguishing MPNSTs from BPNSTs, with a C-index of > 0.9.


Assuntos
Neoplasias da Bainha Neural , Neoplasias do Sistema Nervoso Periférico , Diferenciação Celular , Diagnóstico Diferencial , Imagem de Difusão por Ressonância Magnética , Humanos , Imageamento por Ressonância Magnética , Neoplasias da Bainha Neural/diagnóstico por imagem , Neoplasias do Sistema Nervoso Periférico/diagnóstico , Estudos Retrospectivos , Sensibilidade e Especificidade
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