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1.
Int J Mol Sci ; 25(10)2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38791285

RESUMO

Extracellular vesicles (EVs) have been found to have the characteristics of their parent cells. Based on the characteristics of these EVs, various studies on disease treatment using mesenchymal stem cell (MSC)-derived EVs with regenerative activity have been actively conducted. The therapeutic nature of MSC-derived EVs has been shown in several studies, but in recent years, there have been many efforts to functionalize EVs to give them more potent therapeutic effects. Strategies for functionalizing EVs include endogenous and exogenous methods. In this study, human umbilical cord MSC (UCMSC)-derived EVs were selected for optimum OA treatments with expectation via bioinformatics analysis based on antibody array. And we created a novel nanovesicle system called the IGF-si-EV, which has the properties of both cartilage regeneration and long-term retention in the lesion site, attaching positively charged insulin-like growth factor-1 (IGF-1) to the surface of the UCMSC-derived Evs carrying siRNA, which inhibits MMP13. The downregulation of inflammation-related cytokine (MMP13, NF-kB, and IL-6) and the upregulation of cartilage-regeneration-related factors (Col2, Acan) were achieved with IGF-si-EV. Moreover, the ability of IGF-si-EV to remain in the lesion site for a long time has been proven through an ex vivo system. Collectively, the final constructed IGF-si-EV can be proposed as an effective OA treatment through its successful MMP13 inhibition, chondroprotective effect, and cartilage adhesion ability. We also believe that this EV-based nanoparticle-manufacturing technology can be applied as a platform technology for various diseases.


Assuntos
Vesículas Extracelulares , Fator de Crescimento Insulin-Like I , Células-Tronco Mesenquimais , Osteoartrite , RNA Interferente Pequeno , Fator de Crescimento Insulin-Like I/metabolismo , Vesículas Extracelulares/metabolismo , Humanos , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/citologia , Osteoartrite/terapia , Osteoartrite/metabolismo , RNA Interferente Pequeno/genética , Animais , Metaloproteinase 13 da Matriz/metabolismo , Metaloproteinase 13 da Matriz/genética
2.
Br J Ophthalmol ; 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38418207

RESUMO

BACKGROUND/AIMS: Age-related macular degeneration (AMD) and cancer may share similar risk factors, indicating possible common pathogenic pathways. We aimed to describe the site-specific cancer risk based on the relationship of AMD with visual disability (VD) status. METHODS: This was a population-based cohort study using data from the Korean National Health Insurance Service database (2009-2019) including patients who participated in a national health screening programme in 2009. The subjects were categorised based on the presence of AMD and VD. The occurrence of cancer was identified using principal diagnosis according to the International Classification of Disease, 10th revision codes in claims data. The Cox regression hazard model was used to compare HRs of site-specific cancer. RESULTS: Among 4 088 814 participants, 51 596 had AMD of which 3683 subjects had VD. The mean follow-up period was 9.6 years. The overall cancer risk was generally null, but the risk of hypervascular cancer such as thyroid cancer (adjusted HR (aHR) 1.10, 95% CI 1.00 to 1.20) and renal cancer (aHR 1.16, 95% CI 1.00 to 1.33) was higher and the risk of stomach cancer (aHR 0.89, 95% CI 0.84 to 0.94) was lower in the AMD group than in the non-AMD group. CONCLUSION: This study demonstrated a possible association between AMD and several cancers. Increased renal and thyroid cancer risk among patients with AMD could indicate that AMD is associated with hypervascular cancer. Further studies in which additional databases are used and the underlying detailed mechanisms evaluated are needed to validate our results.

3.
Int J Mol Sci ; 24(24)2023 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-38139268

RESUMO

FJH-KO obtained from Antarctic krill, especially Euphausia superba, has been reported to contain high amounts of omega-3 polyunsaturated fatty acids (n-3 PUFA) and to exhibit anticancer and anti-inflammatory properties. However, its antithrombotic effects have not yet been reported. This study aimed to investigate the antithrombotic effects of FJH-KO in carrageenan-induced thrombosis mouse models and human endothelial cells. Thrombosis was induced by carrageenan injection, whereas the mice received FJH-KO pretreatment. FJH-KO attenuated carrageenan-induced thrombus formation in mouse tissue vessels and prolonged tail bleeding. The inhibitory effect of FJH-KO was associated with decreased plasma levels of thromboxane B2, P-selectin, endothelin-1, ß-thromboglobulin, platelet factor 4, serotonin, TNF-α, IL-1ß, and IL-6. Meanwhile, FJH-KO induced plasma levels of prostacyclin I2 and plasminogen. In vitro, FJH-KO decreased the adhesion of THP-1 monocytes to human endothelial cells stimulated by TNF-α via eNOS activation and NO production. Furthermore, FJH-KO inhibited the expression of TNF-α-induced adhesion molecules such as ICAM-1 and VCAM-1 by suppressing the NF-κB signaling pathway. Taken together, our study demonstrates that FJH-KO protects against carrageenan-induced thrombosis by regulating endothelial cell activation and has potential as an antithrombotic agent.


Assuntos
Euphausiacea , Ácidos Graxos Ômega-3 , Trombose , Humanos , Animais , Camundongos , Carragenina/efeitos adversos , Células Endoteliais/metabolismo , Fibrinolíticos/efeitos adversos , Fator de Necrose Tumoral alfa/metabolismo , Trombose/induzido quimicamente , Trombose/tratamento farmacológico , Ácidos Graxos Ômega-3/efeitos adversos
4.
ACS Omega ; 8(46): 44076-44085, 2023 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-38027389

RESUMO

Melanoma, a highly malignant and aggressive form of skin cancer, poses a significant global health threat, with limited treatment options and potential side effects. In this study, we developed a temperature-responsive hydrogel for skin regeneration with a controllable drug release. The hydrogel was fabricated using an interpenetrating polymer network (IPN) of N-isopropylacrylamide (NIPAAm) and poly(vinyl alcohol) (PVA). PVA was chosen for its adhesive properties, biocompatibility, and ability to address hydrophobicity issues associated with NIPAAm. The hydrogel was loaded with doxorubicin (DOX), an anticancer drug, for the treatment of melanoma. The NIPAAm-PVA (N-P) hydrogel demonstrated temperature-responsive behavior with a lower critical solution temperature (LCST) around 34 °C. The addition of PVA led to increased porosity and faster drug release. In vitro biocompatibility tests showed nontoxicity and supported cell proliferation. The N-P hydrogel exhibited effective anticancer effects on melanoma cells due to its rapid drug release behavior. This N-P hydrogel system shows great promise for controlled drug delivery and potential applications in skin regeneration and cancer treatment. Further research, including in vivo studies, will be essential to advance this hydrogel system toward clinical translation and impactful advancements in regenerative medicine and cancer therapeutics.

5.
Ann Dermatol ; 35(Suppl 1): S176-S177, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37853904
6.
BMC Neurol ; 23(1): 336, 2023 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-37749508

RESUMO

INTRODUCTION: The neutrophil-to-lymphocyte ratio (NLR) has been found to be useful in the prognostication of immune-mediated neurological disorders because it roughly reflects the systemic innate immune response compared to the adaptive immune response. However, studies on the validity of NLR in demyelinating disorders of the central nervous system have shown conflicting results. Therefore, we aimed to investigate NLR in the idiopathic transverse myelitis (ITM) cohort. METHODS: We retrospectively analyzed the cohort data of patients with ITM between January 2006 and February 2020. The medical data of all patients with myelitis were reviewed to exclude patients with disease-associated myelopathy according to predefined exclusion criteria. The relationship between the natural log-transformed NLR (lnNLR) and the clinical, paraclinical, and imaging data was evaluated. Factors associated with neurological disability were analyzed using a linear mixed-effects model. Predictive factors for moderate-to-severe neurological disability (Expanded Disability Status Scale [EDSS] score ≥ 4) were investigated. RESULTS: A total of 124 participants were included in the analysis. The lnNLR correlated with EDSS and lesion length. Linear mixed-effects analysis showed that age, lesion length, and lnNLR were independently associated with neurological disabilities. Multivariable logistic regression revealed that lnNLR (odds ratio [OR] = 4.266, 95% confidence interval [CI] = 1.220-14.912, p = 0.023) and lesion length (OR = 1.848, 95% CI = 1.249-2.734, p = 0.002) were independent predictive factors of the worst neurological disability. CONCLUSION: NLR may be used as an independent prognostic factor for predicting poor neurological outcomes in patients with ITM.


Assuntos
Mielite Transversa , Humanos , Neutrófilos , Estudos Retrospectivos , Linfócitos , Pacientes
7.
Biochem Pharmacol ; 216: 115768, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37652106

RESUMO

Nonalcoholic fatty liver disease (NAFLD) has been linked to fat accumulation in the liver and lipid metabolism imbalance. Sesamin, a lignan commonly found in sesame seed oil, possesses antioxidant, anti-inflammatory, and anticancer properties. However, the precise mechanisms by which sesamin prevents hepatic steatosis are not well understood. This study aimed to explore the molecular mechanisms by which sesamin may improve lipid metabolism dysregulation. A in vitro hepatic steatosis model was established by exposing HepG2 cells to palmitate sodium. The results showed that sesamin effectively mitigated lipotoxicity and reduced reactive oxygen species production. Additionally, sesamin suppressed lipid accumulation by regulating key factors involved in lipogenesis and lipolysis, such as fatty acid synthase (FASN), sterol regulatory element-binding protein 1c (SREBP-1c), forkhead box protein O-1, and adipose triglyceride lipase. Molecular docking results indicated that sesamin could bind to estrogen receptor α (ERα) and reduce FASN and SREBP-1c expression via the Ca2+/calmodulin-dependent protein kinase kinase ß (CaMKKß)/AMP-activated protein kinase (AMPK) signaling pathway. Sesamin attenuated palmitate-induced lipotoxicity and regulated hepatic lipid metabolism in HepG2 cells by activating the ERα/CaMKKß/AMPK signaling pathway. These findings suggest that sesamin can improve lipid metabolism disorders and is a promising candidate for treating hepatic steatosis.


Assuntos
Lignanas , Hepatopatia Gordurosa não Alcoólica , Humanos , Receptor alfa de Estrogênio/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Quinase da Proteína Quinase Dependente de Cálcio-Calmodulina , Simulação de Acoplamento Molecular , Fígado/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Lignanas/farmacologia , Metabolismo dos Lipídeos , Células Hep G2 , Transdução de Sinais , Palmitatos/metabolismo
8.
Health Sci Rep ; 6(2): e1056, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36741853

RESUMO

Background and Aims: Although many angiotensin receptor blockers (ARBs) are widely used, comparative data regarding their impact on clinical outcomes are limited. We aimed to compare the clinical effectiveness of seven ARBs on long-term cardiovascular outcomes in Korean patients with hypertension. Methods: Using the Korean National Health Insurance Service database, the data of 780,785 patients with hypertension without cardiovascular disease (CVD) who initiated ARB treatment (candesartan, fimasartan, irbesartan, losartan, olmesartan, telmisartan, or valsartan) in 2014 and underwent this treatment for more than 6 months, were analyzed. Cox-regression analysis was performed using Losartan as a comparator, as it was the most widely used drug, by adjusting age, sex, diabetes, dyslipidemia, smoking, alcohol drinking, exercise, body mass index, systolic blood pressure, albuminuria, estimated glomerular filtration rate, and concomitant medications. The occurrence of mortality and the rate of major adverse cardiovascular events (MACEs) of the six ARBs was compared with that of losartan. Results: The median follow-up duration was 5.94 (interquartile range, 5.87-5.97) years. In the crude analysis of all-cause mortality and MACEs, fimasartan exhibited the lowest event rates. In the Cox-regression analysis with adjustment, there was no significant difference in all-cause mortality among ARBs. The risk of MACEs with ARBs was similar to that with losartan, although the risks with irbesartan (hazard ratio [HR], 1.079; 95% confidence interval [CI], 1.033-1.127; p = 0.007) and candesartan (HR: 1.066; 95% CI, 1.028-1.106; p = 0.015) were slightly higher. Conclusion: In a Korean population of patients with hypertension without CVD, six different ARBs showed similar efficacy to losartan in terms of long-term mortality and MACEs. Further well-designed prospective studies are required to confirm our findings.

9.
Artigo em Inglês | MEDLINE | ID: mdl-36293597

RESUMO

This study investigated differences in unhealthy lifestyle behaviors (ULBs) between workers and nonworkers and demonstrated the association of ULBs with occupational characteristics among workers. This cross-sectional study used data from the Korea National Health and Nutrition Examination Survey from 2007 to 2019. For sociodemographic data, chi-squared tests were used to analyze categorical variables. Odds ratios (ORs) and 95% confidence intervals (CIs) for ULBs were estimated using Poisson regression models after adjusting for age, sex, educational level, and household income. The variables used were current smoking status, heavy drinking, and physical inactivity. Workers were associated with an increased risk of current smoking (adjusted OR (aOR) = 1.48, 95%CI = 1.41-1.56), heavy drinking (aOR = 1.79, 95%CI = 1.68-1.90), and physical inactivity (aOR = 1.07, 95%CI = 1.04-1.11) compared with nonworkers. Among workers, the differential risks of ULB according to occupational characteristics were as follows: skilled manual workers, self-employed workers, and workers working >40 h/week were at a higher risk of engaging in all ULBs than those in other occupational categories, paid workers, and workers working ≤40 h/week, respectively. Workers showed a higher risk of ULBs than nonworkers. The risk of ULBs differed according to occupational characteristics, highlighting the need for additional studies and detailed occupational health management.


Assuntos
Saúde Ocupacional , Humanos , Inquéritos Nutricionais , Estudos Transversais , Comportamentos Relacionados com a Saúde , República da Coreia/epidemiologia , Nível de Saúde , Fatores de Risco
10.
Toxicol Res ; 38(3): 355-364, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35874500

RESUMO

3-Caffeoyl-4-dicaffeoylquinic acid (CDCQ) is a natural chlorogenic acid isolated from Salicornia herbacea that protects against oxidative stress, inflammation, and cancer. Nitric oxide (NO) plays a physiologically beneficial role in the cardiovascular system, including vasodilation, protection of endothelial cell function, and anti-inflammation. However, the effect of CDCQ on NO production and eNOS phosphorylation in endothelial cells is unclear. We investigated the effect of CDCQ on eNOS phosphorylation and NO production in human endothelial cells, and the underlying signaling pathway. CDCQ significantly increased NO production and the phosphorylation of eNOS at Ser1177. Additionally, CDCQ induced phosphorylation of PKA, CaMKII, CaMKKß, and AMPK. Interestingly, CDCQ increased the intracellular Ca2+ level, and L-type Ca2+ channel (LTCC) blockade significantly attenuated CDCQ-induced eNOS activity and NO production by inhibiting PKA, CaMKII, CaMKKß, and AMPK phosphorylation. These results suggest that CDCQ increased eNOS phosphorylation and NO production by Ca2+-dependent phosphorylation of PKA, CaMKII, CaMKKß, and AMPK. Our findings provide evidence that CDCQ plays a pivotal role in the activity of eNOS and NO production, which is involved in the protection of endothelial dysfunction.

11.
Phytother Res ; 36(9): 3601-3618, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35871535

RESUMO

Puerarin, the major bioactive ingredient isolated from the root of Pueraria lobata (Willd.), attenuates body weight gain and reduces lipid levels in high-fat diet-induced obese mice; however, the underlying mechanism responsible for regulating lipid metabolism remains unclear. This study investigated the molecular mechanism(s) underlying the role of puerarin in regulating lipogenesis and lipolysis in human HepG2 cells. In this study, puerarin strongly inhibited the expression of fatty acid synthase (FASN) and sterol regulatory element binding protein 1c (SREBP-1c). Moreover, puerarin significantly induced the expression of adipose triglyceride lipase (ATGL), which is responsible for triacylglycerol hydrolase activity in cells. Puerarin enhanced 5' AMP-activated protein kinase (AMPK) activity, which is a central regulator of hepatic lipid metabolism. Furthermore, this AMPK activation could be mediated by sirtuin 1 (SIRT1) and calcium signaling pathways involved in G protein-coupled estrogen receptor (GPER) signaling. GPER blockage significantly reversed the effect of puerarin on lipid accumulation and the related signaling pathways. Docking studies showed that puerarin could bind in the GPER in a similar manner as GPER agonist G1. Our results suggest that puerarin can improve hepatic steatosis by activating GPER; it's signaling cascade sequentially induced calcium and SIRT1 signaling pathways. Thus, puerarin may be a potential therapeutic agent for the treatment of non-alcoholic fatty liver disease.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Sirtuína 1 , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Cálcio/metabolismo , Proteínas de Ligação ao GTP/metabolismo , Proteínas de Ligação ao GTP/farmacologia , Células Hep G2 , Humanos , Isoflavonas , Metabolismo dos Lipídeos , Lipídeos , Fígado , Camundongos , Camundongos Obesos , Hepatopatia Gordurosa não Alcoólica/metabolismo , Receptores de Estrogênio/metabolismo , Transdução de Sinais , Sirtuína 1/metabolismo
12.
J Clin Med ; 11(6)2022 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-35330049

RESUMO

This study investigated whether changes in work schedule are associated with health behavior changes. We used data from the Korea Labor and Income Panel Survey from 2005 to 2019. A generalized estimating equation model was used to assess the association between changes of work schedules (day-day, day-shift, shift-day, and shift-shift) and health behaviors. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated after adjusting for general and socioeconomic characteristics. Fixed daytime work was observed for 25,716 person-years, and fixed shift work was observed for 2370 person-years out of the total 4046 participants during a 14 year period. Workers who changed their work schedule from fixed daytime to shift work and from shift to fixed daytime work contributed to 670 and 739 person-years, respectively. Considering continuous fixed daytime workers as a reference group, continuous exposure to shift work (aOR 1.11, CI 1.01-1.26) and changes from fixed daytime to shift work (aOR 1.18, CI 1.05-1.44) were significantly associated with an increased risk of changing either smoking or drinking behavior to unhealthy patterns. The results of our study suggest that workers who work irregular shift times, in contrast to those with more standard, regular work schedules, are at a higher risk of changing smoking and/or drinking behavior to unhealthy patterns.

13.
Int J Mol Sci ; 23(2)2022 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-35054804

RESUMO

The white-rot fungi Ceriporia lacerata is used in bioremediation, such as lignocellulose degradation, in nature. Submerged cultures and extracts of C. lacerata mycelia (CLM) have been reported to contain various active ingredients, including ß-glucan and extracellular polysaccharides, and to exert anti-diabetogenic properties in mice and cell lines. However, the immunostimulatory effects have not yet been reported. This study aimed to identify the immunomodulatory effects, and underlying mechanisms thereof, of submerged cultures of CLM using RAW264.7 macrophages and cyclophosphamide (CTX)-induced immunosuppression in mice. Compared to CTX-induced immunosuppressed mice, the spleen and thymus indexes in mice orally administered CLM were significantly increased; body weight loss was alleviated; and natural killer (NK) cytotoxicity, lymphocyte proliferation, and cytokine (tumor necrosis factor [TNF]-α, interferon [IFN]-γ, and interleukin [IL]-2) production were elevated in the serum. In RAW264.7 macrophages, treatment with CLM induced phagocytic activity, increased the production of nitric oxide (NO), and promoted mRNA expression of the immunomodulatory cytokines TNF-α, IFN-γ, IL-1ß, IL-6, IL-10, and IL-12. In addition, CLM increased the inducible NO synthase (iNOS) concentration in macrophages, similar to lipopolysaccharide (LPS) stimulation. Mechanistic studies showed that CLM induced the activation of the NF-κB, PI3k/Akt, ERK1/2, and JNK1/2 pathways. Moreover, the phosphorylation of NF-κB and IκB induced by CLM in RAW264.7 cells was suppressed by specific MAPKs and PI3K inhibitors. Further experiments with a TLR4 inhibitor demonstrated that the production of TNF-α, IL-1ß, and IL-6 induced by CLM was decreased after TLR4 was blocked. Overall, CLM protected against CTX-induced adverse reactions by enhancing humoral and cellular immune functions, and has potential as an immunomodulatory agent.


Assuntos
Citocinas/sangue , Agentes de Imunomodulação/farmacologia , Terapia de Imunossupressão , Macrófagos/efeitos dos fármacos , Micélio/química , Polyporales/química , Animais , Ciclofosfamida/toxicidade , Citocinas/metabolismo , Macrófagos/imunologia , Macrófagos/metabolismo , Masculino , Camundongos , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Células RAW 264.7 , Transdução de Sinais
14.
Pathol Oncol Res ; 27: 622733, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34257587

RESUMO

Gastric cancer has the fifth-highest incidence rate and is the third leading cause of cancer-related deaths worldwide. The incidence of gastric cancer is higher in men than in women, but for the diffuse types of gastric cancer, the trend is opposite. Estrogen is considered the prime culprit behind these differences. Nevertheless, the action of estrogen in gastric cancers remains unclear. In this study, we investigated the effect of estrogen on diffuse-type gastric cancer. Human female diffuse gastric cancer SNU-16 cells were transplanted into male and female mice to analyze the effect of endogenous estrogen on tumor growth. Furthermore, the effect of exogenous estrogen was evaluated in ovariectomized mice. Expressed genes were compared between female and male xenograft models using RNA sequencing analysis. Furthermore, human gene expression omnibus databases were utilized to examine the effect of our target genes on overall survival. SNU-16-derived tumor growth was faster in female mice than in male mice. In total RNA sequencing, interferon gamma receptor 2 (IFNGR2), IQ motif containing E (IQCE), transient receptor potential cation channel subfamily M member 4 (TRPM4), and structure-specific endonuclease subunit SLX4 (SLX4) were found. These genes could be associated with the tumor growth in female diffuse-type gastric cancer which was affected by endogenous estrogen. In an ovariectomized gastric cancer xenograft model, exogenous estrogen promoted tumor growth. Especially, our results indicated that estrogen induced G protein-coupled estrogen receptor expression in these mice. These results suggest that estrogen aggravates tumor progression in female diffuse gastric cancer.


Assuntos
Biomarcadores Tumorais/genética , Estrogênios/toxicidade , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Neoplasias Gástricas/patologia , Transcriptoma , Animais , Apoptose , Proliferação de Células , Feminino , Humanos , Masculino , Camundongos , Camundongos Nus , Neoplasias Gástricas/induzido quimicamente , Neoplasias Gástricas/genética , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
15.
J Cell Physiol ; 236(10): 7014-7032, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33748944

RESUMO

Cancer-associated fibroblasts (CAFs) in the tumor microenvironment have been associated with tumor progression in breast cancer. Although crosstalk between breast cancer cells and CAFs has been studied, the effect of CAFs on non-neoplastic breast epithelial cells is not fully understood to date. Here, we investigated the effect of CAFs on aggressive phenotypes in non-neoplastic MCF10A breast epithelial cells. CAFs induced epithelial-to-mesenchymal transition (EMT) and invasive phenotype in MCF10A cells. S100A8, a potential prognostic marker in several cancers, was markedly increased in MCF10A cells by CAFs. S100A8 was crucial for CAFs-induced invasive phenotype of MCF10A cells. Among cytokines increased by CAFs, interleukin (IL)-8 induced S100A8 through transcription factors p65 NF-κB and C/EBPß. In a xenograft mouse model with MCF10A cells and CAFs, tumor was not developed, suggesting that coinjection with CAFs may not be sufficient for in vivo tumorigenicity of MCF10A cells. Xenograft mouse tumor models with MDA-MB-231 breast carcinoma cells provided an in vivo evidence for the effect of CAFs on breast cancer progression as well as a crucial role of IL-8 in tumor growth and S100A8 expression in vivo. Using a tissue microarray of human breast cancer, we showed that S100A8 expression was correlated with poor outcomes. S100A8 expression was more frequently detected in cancer-adjacent normal human breast tissues than in normal breast tissues. Together, this study elucidated a novel mechanism for the acquisition of invasive phenotype of non-neoplastic breast cells induced by CAFs, suggesting that targeting IL-8 and S100A8 may be an effective strategy against breast cancer.


Assuntos
Neoplasias da Mama/metabolismo , Calgranulina A/metabolismo , Fibroblastos Associados a Câncer/metabolismo , Células Epiteliais/metabolismo , Interleucina-8/metabolismo , Comunicação Parácrina , Animais , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Proteína beta Intensificadora de Ligação a CCAAT/genética , Proteína beta Intensificadora de Ligação a CCAAT/metabolismo , Calgranulina A/genética , Fibroblastos Associados a Câncer/efeitos dos fármacos , Fibroblastos Associados a Câncer/patologia , Linhagem Celular Tumoral , Movimento Celular , Técnicas de Cocultura , Células Epiteliais/patologia , Transição Epitelial-Mesenquimal , Feminino , Humanos , Interleucina-8/genética , Camundongos Endogâmicos BALB C , Camundongos Nus , Invasividade Neoplásica , Fenótipo , Transdução de Sinais , Sulfonamidas/farmacologia , Fator de Transcrição RelA/genética , Fator de Transcrição RelA/metabolismo , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
16.
J Bone Joint Surg Am ; 102(24): 2129-2137, 2020 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-33044249

RESUMO

BACKGROUND: The use of platelet-rich plasma (PRP) for the treatment of rotator cuff disease is still controversial. The purpose of the present study was to investigate the safety and efficacy of a fully characterized allogeneic pure PRP injection into the subacromial space of patients with rotator cuff disease in comparison with corticosteroid injection. METHODS: A 2-group, parallel, assessor-blinded, randomized controlled trial was conducted. A total of 60 patients with clinically and structurally diagnosed rotator cuff disease were randomly assigned to receive a subacromial injection of either 4 mL of allogeneic pure PRP or a 4-mL mixture of 1 mL of 40-mg/mL triamcinolone acetonide and 3 mL of 2% lidocaine under ultrasonographic guidance. The primary outcomes were safety and the Constant score at 1 month. The secondary outcomes were pain, range of motion, muscle strength, functional scores, and overall satisfaction and function. RESULTS: There were no treatment-related adverse events. The Constant score at 1 month did not significantly differ between the PRP and corticosteroid groups. At 6 months, the DASH (Disabilities of the Arm, Shoulder and Hand) score, overall function, and external rotation were significantly better in the PRP group than in the corticosteroid group, and the other clinical outcomes did not show significant differences. All pain measurements, the strength of the supraspinatus and infraspinatus, and 5 functional scores also improved slowly and steadily after injection, becoming significantly better at 6 months compared with those before the injection, whereas those in the corticosteroid group responded promptly but did not further improve. CONCLUSIONS: Allogeneic PRP injections for the treatment of rotator cuff disease are safe but are not definitely superior to corticosteroid injections with respect to pain relief and functional improvement during 6 months. The DASH score, overall function, and external rotation were significantly better in the PRP group than in the steroid group at 6 months. Generally, PRP slowly but steadily reduced pain and improved function of the shoulder until 6 months, whereas corticosteroid did not. LEVEL OF EVIDENCE: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.


Assuntos
Corticosteroides/uso terapêutico , Plasma Rico em Plaquetas , Lesões do Manguito Rotador/terapia , Triancinolona/uso terapêutico , Corticosteroides/administração & dosagem , Feminino , Humanos , Injeções/métodos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Lesões do Manguito Rotador/tratamento farmacológico , Resultado do Tratamento , Triancinolona/administração & dosagem , Ultrassonografia de Intervenção
17.
J Nutr Educ Behav ; 52(5): 492-502, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32094023

RESUMO

OBJECTIVE: Explore the availability of food options and nutrition education at food pantries and identify the barriers to offering them to pantry clients. DESIGN: Cross-sectional, mixed-methods study. SETTING: Food pantry, Cincinnati, OH. PARTICIPANTS: A total of 41 food pantry coordinators (aged 63.4 ± 9.1 years), recruited by e-mail/phone in an urban area. PHENOMENON OF INTEREST: Availability of food options and nutrition education and barriers to improving food options and providing nutrition education at food pantries. ANALYSIS: Survey data were collected using Qualtrics and analyzed using SPSS software. In-depth interviews were transcribed verbatim, transcripts were independently coded, and codes and themes were discussed until a consensus was reached. RESULTS: The availability of fresh produce, dairy, low-sodium canned vegetables, and whole grains were limited, and 10 food pantries (24%) offered nutrition education to their clients. Challenges to improving food options were lack of space and equipment for storage and transportation. Identified barriers to providing nutrition education included the lack of space, funding, personnel with nutrition expertise, and clients' low interest in nutrition education. CONCLUSIONS AND IMPLICATIONS: The availability of healthy food choices and nutrition education were limited at local food pantries. Collaborative efforts with community partners and nutrition experts may be necessary to overcome those barriers.


Assuntos
Abastecimento de Alimentos , Educação em Saúde , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Dieta Saudável , Feminino , Assistência Alimentar , Promoção da Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Verduras
18.
Korean J Fam Med ; 41(6): 422-426, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31902197

RESUMO

BACKGROUND: This study aimed to examine the association between sitting time and handgrip strength in healthy Korean women. METHODS: A total of 5,437 participants were included from the Korea National Health and Nutrition Examination Survey 2014-2016. The overall daily sitting time was estimated using health interview surveys, and handgrip strength was assessed using a digital hand dynamometer. The relationship between sitting time and handgrip strength was calculated with a weighted analysis of covariance after adjusting for confounding variables. RESULTS: Participants in each age group (19-39, 40-64, ≥65 years) were divided into three categories according to sitting time: ≤5, 6-9, and ≥10 h/d. The handgrip strength tended to decrease as sitting time increased after adjusting for age, body mass index, alcohol intake, cigarette smoking, resistance exercise, aerobic physical activity, household income, education level, hypertension, diabetes mellitus, dyslipidemia, and depression in all age groups (all P<0.001). CONCLUSION: We observed the inverse relationship between sitting time and handgrip strength in healthy Korean women.

19.
Front Pharmacol ; 9: 1325, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30524282

RESUMO

Polycystic ovary syndrome (PCOS) is an endocrinal disorder that afflicts mainly women of childbearing age. The symptoms of PCOS are irregular menstrual cycles, weight gain, subfertility and infertility. However, because the etiology is unclear, management and treatment methods for PCOS are not well established. Recently, natural substances have been used for PCOS therapy. Ecklonia cava (E. cava) is a well-known natural substance that attenuates the effects of inflammation, allergies, and cancer. In this study, we investigated the effects of E. cava extract in rats with PCOS. When rats with letrozole-induced PCOS were exposed to the E. cava extract, the regular estrus cycle was restored, similar to that in placebo rats. Hormone levels, including the levels of testosterone, estrogen, luteinizing hormone (LH), follicle stimulating hormone (FSH), and anti-Müllerian hormone (AMH), were restored to their normal states. Histological analysis revealed that the polycystic ovary symptoms were significantly decreased in the E. cava-treated rats and were comparable to those of normal ovaries. At the transcriptional and translational levels, Ar, and Esr2 levels were markedly increased in the E. cava-treated rats with PCOS compared with the rats with letrozole-induced PCOS. These results suggest that the E. cava extract inhibits the symptoms of PCOS by restoring imbalanced hormonal levels and irregular ovarian cycles in letrozole-induced female rats.

20.
Biotechnol Bioeng ; 115(11): 2817-2827, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29981260

RESUMO

Hepatic steatosis is a process of abnormal lipid deposition within the liver cells, often caused by excessive alcohol uptake or obesity. A conventional in vitro model for hepatic steatosis uses a liver cell culture, treated with fatty acids and measures accumulation of lipids within the cells. This model does not recapitulate the complex process of absorption and metabolism of digestive lipids. Here, we introduce a gut-liver chip, which mimics the gut absorption and hepatic metabolism in a microfluidic chip. Absorption of fatty acids through gut layer and subsequent deposition within liver cells was demonstrated. Tumor necrosis factor-α, butyrate, and α-lipoic acid were chosen as model molecules that can affect hepatic steatosis via different mechanisms, and their effects were evaluated. Our results suggest that the gut-liver chip can mimic the absorption and accumulation of fatty acids in the gut and the liver.


Assuntos
Fígado Gorduroso/patologia , Trato Gastrointestinal/patologia , Dispositivos Lab-On-A-Chip , Metabolismo dos Lipídeos , Microfluídica/métodos , Butiratos/metabolismo , Células CACO-2 , Células Hep G2 , Humanos , Microfluídica/instrumentação , Ácido Tióctico/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
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