Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 127
Filtrar
1.
Qual Life Res ; 33(5): 1287-1295, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38321193

RESUMO

PURPOSE: This study evaluated the association between social support during the re-entry period and long-term health-related quality of life (HRQoL) in breast cancer survivors using a longitudinal cohort study. METHODS: This is a prospective cohort study with 275 breast cancer survivors who reported HRQoL at 5 and 10 years after diagnosis. Social support for the re-entry period was measured 3 years after diagnosis using the Medical Outcome Study Social Support Survey (MOS-SSS). HRQoL was evaluated using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) and Breast Cancer-Specific Module (BR-23). Multivariable linear regression analysis was performed to evaluate HRQoL at 5 and 10 years after diagnosis by level of social support during the re-entry period. RESULTS: The mean (SD) of social support during re-entry period was 68.5. The low social support (LSS, score < 55) group during the re-entry period had a significantly lower HRQoL (mean difference = - 12.93) compared to moderate or high social support (MHSS, score ≥ 55) group. 5 and 10 years after diagnosis, the LSS group continued to demonstrate lower HRQoL (5 years: - 7.17; 10 years: - 7.85) compared to the MHSS group. The LSS group were more likely to have lower role and social function scores, and higher fatigue, pain, and financial problems compared to the MHSS group at 10 years after diagnosis. CONCLUSIONS: Breast cancer survivors who received lower social support during the re-entry period were more likely to experience poorer HRQoL in the long term than those who did not.


Assuntos
Neoplasias da Mama , Sobreviventes de Câncer , Qualidade de Vida , Apoio Social , Humanos , Qualidade de Vida/psicologia , Feminino , Neoplasias da Mama/psicologia , Pessoa de Meia-Idade , Estudos Longitudinais , Sobreviventes de Câncer/psicologia , Estudos Prospectivos , Inquéritos e Questionários , Adulto , Idoso
2.
Int J Mol Sci ; 25(3)2024 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-38338851

RESUMO

The most commonly used chemotherapy for colorectal cancer (CRC) is the application of 5-fluorouracil (5-FU). Inhibition of thymidylate synthase (TYMS) expression appears to be a promising strategy to overcome the decreased sensitivity to 5-FU caused by high expression of TYMS, which can be induced by 5-FU treatment. Several compounds have been shown to potentially inhibit the expression of TYMS, but it is unclear whether short-chain fatty acids (SCFAs), which are naturally produced by bacteria in the human intestine, can regulate the expression of TYMS. Sodium butyrate (NaB) is the most widely known SCFA for its beneficial effects. Therefore, we investigated the enhancing effects on inhibition of cell viability and induction of apoptosis after co-treatment of NaB with 5-FU in two CRC cell lines, HCT116 and LoVo. This study suggests that the effect of NaB in improving therapeutic sensitivity to 5-FU in CRC cells may result from a mechanism that strongly inhibits the expression of TYMS. This study also shows that NaB inhibits the migration of CRC cells and can cause cell cycle arrest in the G2/M phase. These results suggest that NaB could be developed as a potential therapeutic adjuvant to improve the therapeutic effect of 5-FU in CRC.


Assuntos
Neoplasias Colorretais , Timidilato Sintase , Humanos , Ácido Butírico/farmacologia , Timidilato Sintase/genética , Timidilato Sintase/metabolismo , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/metabolismo , Resistencia a Medicamentos Antineoplásicos , Fluoruracila/farmacologia , Fluoruracila/uso terapêutico , Apoptose
3.
Int J Mol Sci ; 25(6)2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38542316

RESUMO

Nardostachys jatamansi is widely used as a traditional medicine in Asian countries. Numerous recent studies have reported the biological activities of its secondary metabolites and extracts. In this study, a total of 14 components were isolated, including cycloolivil and 2-(3'-hydroxy-5'-ethoxyphenyl)-3-hydroxylmethyl-7-methoxy-2,3-dihydrobenzofuran-5-carboxylic acid, which were first discovered in N. jatamansi. The isolated compounds were investigated for their anti-inflammatory effects on HaCaT keratinocytes and their potential to alleviate skin inflammation. The results of the screening revealed that cycloolivil and 4ß-hydroxy-8ß-methoxy-10-methylene-2,9-dioxatricyclo[4.3.1.03,7]decane reduced the production of inflammatory cytokines induced by TNF-α/IFN-γ, such as IL-6, IL-8, and RANTES, in keratinocytes. This study focused on exploring the biological effects of cycloolivil, and the results suggested that cycloolivil inhibits the expression of COX-2 proteins. Further mechanistic evaluations confirmed that the anti-inflammatory effects of cycloolivil were mediated by blockage of the NF-κB and JAK/STAT signaling pathways. These results suggest that cycloolivil isolated from N. jatamansi could be used to treat skin inflammatory diseases.


Assuntos
NF-kappa B , Nardostachys , Fenóis , NF-kappa B/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Nardostachys/metabolismo , Interferon gama/metabolismo , Queratinócitos/metabolismo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/metabolismo
4.
Geriatr Nurs ; 57: 117-122, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38640645

RESUMO

Effective staff-patient communication is critical in acute care settings, particularly for patients with dementia. Limited work has examined the impact of quality of staff-patient care interactions on patient engagement. The purpose of this study was to determine whether the quality of staff-patient care interactions were associated with active patient engagement during the interaction after controlling for relevant covariates. The study was a secondary data analysis using baseline data from the Function Focused Care for Acute Care intervention study, with a total sample of 286 patients. Descriptive statistics and a generalized linear mixed model were used. The findings indicated that there was a significant relationship between the quality of care interactions and patient engagement such that receiving positive care interactions resulted in higher odds of active patient engagement. These findings can inform future interventions and training for acute care staff to improve quality of care interactions and patient engagement.


Assuntos
Demência , Participação do Paciente , Qualidade da Assistência à Saúde , Humanos , Demência/enfermagem , Masculino , Feminino , Idoso , Comunicação , Idoso de 80 Anos ou mais , Relações Profissional-Paciente
5.
Small ; : e2307542, 2023 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-38044288

RESUMO

With the rapid development of human-friendly wearable devices, energy storage components are required to have skin-like stretchability or free-form to fit closer and more comfortably to the human body. This study introduces a hierarchically interpenetrated reentrant microcellular structure combined with 2D cellular graphene/MXene/carbon nanotubes (CNTs) and 3D cellular melamine foam. This composite structure works as a stretchable framework of lithium metal composite electrodes to provide stretchability for lithium metal electrodes, which are promising as next-generation energy storage systems. The interpenetrated but independent cellular structures successfully obtain stable structural deformability from the nonconductive and deformable melamine foam, while at the same time, high electrical conductivity, lithiophilicity, and mechanical stability of the graphene/CNT/MXene network serve as a lithium deposition support during the electrodeposition of lithium. The reentrant structure is fabricated by radial compressing the hierarchical cellular structures to take advantage of the structural stretchability of the accordion-like reentrant frameworks. The lithium-deposited composite electrodes exhibit much lower overpotential during Li stripping and plating than lithium metal foil anodes and show stable electrochemical performances under 30% of mechanical strain. The reentrant microcellular electrodes offer great potential for advanced designs of lithium metal electrodes for stretchable batteries with high energy density.

6.
Insect Mol Biol ; 32(6): 703-715, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37702106

RESUMO

Animal growth is controlled by a variety of external and internal factors during development. The steroid hormone ecdysone plays a critical role in insect development by regulating the expression of various genes. In this study, we found that fat body-specific expression of miR-276a, an ecdysone-responsive microRNA (miRNA), led to a decrease in the total mass of the larval fat body, resulting in significant growth reduction in Drosophila. Changes in miR-276a expression also affected the proliferation of Drosophila S2 cells. Furthermore, we found that the insulin-like receptor (InR) is a biologically relevant target gene regulated by miR-276a-3p. In addition, we found that miR-276a-3p is upregulated by the canonical ecdysone signalling pathway involving the ecdysone receptor and broad complex. A reduction in cell proliferation caused by ecdysone was compromised by blocking miR-276a-3p activity. Thus, our results suggest that miR-276a-3p is involved in ecdysone-mediated growth reduction by controlling InR expression in the insulin signalling pathway.


Assuntos
Proteínas de Drosophila , Insulinas , MicroRNAs , Animais , Drosophila/genética , Ecdisona/metabolismo , MicroRNAs/genética , Regulação da Expressão Gênica no Desenvolvimento , Proteínas de Drosophila/genética , Insulinas/genética , Insulinas/metabolismo , Drosophila melanogaster/genética
7.
Int J Geriatr Psychiatry ; 38(2): e5885, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36734152

RESUMO

OBJECTIVES: The aims of this study were to: (1) describe the prevalence of behavioral and psychological symptoms of dementia in hospitalized older adults living with dementia and (2) examine the association of physical activity and behavioral and psychological symptoms of dementia among hospitalized older adults living with dementia, after controlling for covariates. METHODS: Physical activity was measured using the Physical Activity Survey and behavioral and psychological symptoms of dementia were measured using the Neuropsychiatric Inventory. Descriptive analysis and multiple linear regressions were run using baseline data on 294 older adults with dementia hospitalized on general medical units from an ongoing study entitled Function Focused Care for Acute Care Using the Evidence Integration Triangle. RESULTS: Participants performed an average of 7.92 (SD = 4.49) of 34 possible activities "in the last 24 h" prior to the Physical Activity Survey administration. A total of 132 participants (45.5%) had at least one behavioral and psychological symptom of dementia. We found that physical activity was not associated with behavioral and psychological symptoms of dementia (b = 0.01; p = 0.56), after controlling for covariates. CONCLUSIONS: Although this study found no evidence of an association between physical activity and behavioral and psychological symptoms of dementia, evidence of physical activity did not exacerbate these behaviors. Thus, given the benefits of physical activity, it is important to continue to encourage patients living with dementia to engage in activity.


Assuntos
Demência , Humanos , Idoso , Demência/psicologia , Sintomas Comportamentais/epidemiologia , Sintomas Comportamentais/psicologia
8.
J Aging Phys Act ; 31(4): 658-665, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-36746152

RESUMO

Older adults continue to spend little time engaged in physical activity when hospitalized. The purpose of this study was to (a) describe activity among hospitalized older adults with dementia and (b) identify the association between specific factors (gender, ambulation independence, comorbidities, race, and hospital setting) and their physical activity. This descriptive study utilized baseline data on the first 79 participants from the Function Focused Care for Acute Care using the Evidence Integration Triangle. Multiple linear regression models were run using accelerometry data from the first full day of hospitalization. The participants spent an average of 83.7% of their time being sedentary. Male gender, ambulation independence, and hospital setting (the hospital in which the patient was admitted) were associated with greater activity. This study reports on the limited time spent in activity for older adults with dementia when hospitalized and highlights patient profiles that are particularly vulnerable to sedentary behavior in the hospital setting.


Assuntos
Demência , Exercício Físico , Humanos , Masculino , Idoso , Caminhada , Hospitalização , Fatores de Tempo , Acelerometria
9.
Molecules ; 28(21)2023 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-37959718

RESUMO

Neuroinflammation activated by microglia affects inflammatory pain development. This study aimed to explore the anti-inflammatory properties and mechanisms of 1,6,7-trihydroxy-2-(1,1-dimethyl-2-propenyl)-3-methoxyxanthone (THMX) from Cudrania tricuspidata in microglia activation-mediated inflammatory pain. In RAW 264.7 and BV2 cells, THMX has been shown to reduce lipopolysaccharide (LPS)-induced inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and pro-inflammatory mediators and cytokines, including nitric oxide (NO), prostaglandin (PG) E2, interleukin (IL)-6, and tumor necrosis factor alpha (TNF-α). THMX also decreased LPS-induced phosphorylation of mitogen-activated protein kinase (MAPK) and the activation of p65 nuclear factor kappa B (NF-κB). Interestingly, THMX also activated heme oxygenase (HO)-1 expression. These findings suggest that THMX is a promising biologically active compound against inflammation through preventing MAPKs and NF-ĸB and activating HO-1 signaling pathways.


Assuntos
Moraceae , NF-kappa B , NF-kappa B/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Lipopolissacarídeos/farmacologia , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/metabolismo , Transdução de Sinais , Microglia/metabolismo , Interleucina-6/metabolismo , Dor/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Ciclo-Oxigenase 2/metabolismo
10.
Int J Environ Health Res ; 33(12): 1479-1489, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35854640

RESUMO

Fine particulate matter (PM2.5) is an air pollutant that causes severe lung injury. We investigated the effects of Jujuboside B (JB), a component of Zizyphi Spinosi Semen, on lung toxicity caused by PM2.5, and we identified the mechanism of its protective effect. Lung injury in an animal model was induced by intratracheal administration of a PM2.5 suspension. After 2 days of PM2.5 pretreatment, mice were administered JB via the tail vein three times over a 2-day period. JB significantly reduced the histological lung damage as well as the lung wet/dry weight ratio. JB also considerably reduced PM2.5-induced autophagy dysfunction, apoptosis, inflammatory cytokine levels, and the number of PM2.5-induced lymphocytes in the bronchial alveolar fluid. We conclude that by regulating TLR2, 4-MyD88, and mTOR-autophagy pathways, JB exerts a protective effect on lung injury. Thus, JB can be used as a potential therapeutic agent for PM2.5-induced lung damage.


Assuntos
Lesão Pulmonar , Saponinas , Camundongos , Animais , Lesão Pulmonar/induzido quimicamente , Lesão Pulmonar/tratamento farmacológico , Pulmão , Saponinas/toxicidade , Saponinas/metabolismo , Material Particulado/toxicidade
11.
BMC Cancer ; 22(1): 917, 2022 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-36008854

RESUMO

BACKGROUND: While many studies investigated changes in working status in cancer survivors, most studies have been performed in survivors of breast cancer and few studies evaluated factors associated with changes in the working status of cancer survivors comprehensively. We aimed to evaluate the changes in the working status of cancer survivors after diagnosis and socio-demographic, clinical, work-related and psychological factors associated with it. METHODS: We conducted a cross-sectional survey of adult patients with cancer who were working at the time of diagnosis. A trained interviewer inquired about participants' current working status, including leave of absence, discontinuing, continuing, and changing work. Sociodemographic, clinical, work-related and psychological factors were measured. Multinomial logistic regression was used to identify factors associated with changes in the working status. RESULTS: Among the 730 patients, 29%, 18% and 6% were currently on a discontinued working, leave of absence and had changed jobs, respectively. Patients who discontinued working after cancer diagnosis were more likely to be female, have ≥ $3,000 of monthly family income, not be the principal wage earners for their families and be blue-collar workers. In clinical characteristics, advanced-stage cancer and experienced cancer recurrence was associated with leave of absence and discontinued working. In work-related and psychological factors, stress due to insufficient job control (relative risk ratio [RRR] = 2.26), interpersonal conflict (RRR = 1.86), job insecurity (RRR = 2.63), organizational system (RRR = 3.49), and lack of reward (RRR = 11.76), and less meaning to work were more likely to discontinue working after a cancer diagnosis. CONCLUSION: Occupational health care professionals and other stakeholders need to openly communicate with patients with cancer about potential barriers during the return-to-work trajectory.


Assuntos
Sobreviventes de Câncer , Recidiva Local de Neoplasia , Adulto , Estudos Transversais , Demografia , Feminino , Humanos , Masculino , Retorno ao Trabalho
12.
Support Care Cancer ; 30(6): 4917-4926, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35174421

RESUMO

PURPOSE: To assess objective financial burden (OFB) and subjective financial distress (SFD) amikong working-age cancer survivors and evaluate their association with spiritual well-being and health-related quality of life (HRQoL). METHODS: This is a multicenter cross-sectional survey of cancer survivors working at diagnosis between 2017 and 2018. OFB was defined as patients with high medical payments for individuals/households, debt due to cancer care costs, or bankruptcy. SFD was measured using a questionnaire. Fear of cancer recurrence (FCR), spiritual well-being, and HRQoL were also assessed. RESULTS: Among 727 participants, 31% reported that they experienced financial toxicity, and 12% and 26% had OFB and SFD, respectively. The No-OFB-SFD, OFB-No-SFD, and OFB-SFD groups were 4.90, 1.82, and 7.81 times more likely to experience uncertainty than the No-OFB-No-SFD group. Furthermore, the No-OFB-SFD, OFB-No-SFD, and OFB-SFD groups were 1.92, 1.35, and 2.53 times more likely to report lost purpose of life, respectively. Overall QoL and health status in the No-OFB-No-SFD, No-OFB-SFD, OFB-No-SFD, and OFB-SFD groups were 63.1, 42.9, 57.0, and 41.2, respectively. Survivors who had SFD regardless of OFB had lower HRQoL and functioning, and higher symptoms than those of the survivors without SFD. CONCLUSION: Financial toxicity was associated with FCR, uncertainty, loss of purpose, and loss of hope among working-age cancer survivors, even in a universal care setting. It is associated with FCR, uncertainty, loss of purpose, and loss of hope. It is necessary to inform survivors of the financial implications of cancer care to allow them to prepare financially as needed.


Assuntos
Sobreviventes de Câncer , Neoplasias , Estudos Transversais , Estresse Financeiro , Humanos , Qualidade de Vida
13.
Support Care Cancer ; 30(1): 721-729, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34368886

RESUMO

PURPOSE: This study aim was to evaluate efficacy of the combination with cosmetic and psychosocial education program on body image, sexual function, and emotional function among young-onset breast cancer (YBC). METHODS: An unblended, randomized, controlled trial design was conducted in patients newly diagnosed with stage I-III breast cancer from 2014 to 2015. The intervention group received a structured education program including appearance management and mind control for 4 weeks. The outcome of this study shows effect on body image and sexual functioning and a distress due to altered appearance and anxiety after the intervention and 6 months after intervention. RESULTS: Among 228 eligible patients, 109 (47.8%) agreed to participate in the present study and were randomized to intervention (n = 54) or control (n = 55) groups. After intervention, the intervention group reported significantly better body image compared to the control group (mean score of 75.0 vs. 59.3, respectively; P < 0.01). The intervention group also reported significantly lower levels of distress due to altered appearance and higher levels of sexual functioning compared to the control group after the intervention. The effects were maintained even 6 months after intervention. CONCLUSION(S): Body image intervention for YBC had effect on improving body image and sexual functioning and a reduction in distress due to altered appearance and anxiety. Trial registration number and date of registration: The study was registered at the Clinical Research Information Service (no. KCT0001191, https://cris.nih.go.kr/cris ) on 23 July 2014.


Assuntos
Neoplasias da Mama , Qualidade de Vida , Ansiedade/etiologia , Imagem Corporal , Neoplasias da Mama/terapia , Escolaridade , Feminino , Humanos
14.
Behav Sleep Med ; 20(1): 50-62, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-33522299

RESUMO

OBJECTIVE/BACKGROUND: Personality traits are regarded as risk factors for cognitive impairment in older adults, while sleep disturbance and physical inactivity are also considered as modifiable risk factors. Therefore, it could be beneficial to investigate the effects of those modifiable risk factors on the relationship between personality traits and cognitive functions, to prepare appropriate strategies for mitigating cognitive impairment. PARTICIPANTS: A total of 155 cognitively unimpaired older adults were included. METHODS: All participants underwent cognitive function tests using the Seoul Neuropsychological Screening Battery and examinations for personality traits using the Big Five Inventory. Individual physical activity and sleep quality were assessed using the International Physical Activity Questionnaire and Pittsburgh Sleep Quality Index, respectively. A hierarchical linear multiple regression analysis was performed to demonstrate the direct association between personality traits and cognitive functions, and the multiple moderator analysis was used to analyze the moderating effects of lifestyle factors on this association. RESULTS: Among the five personality traits, only neuroticism was negatively associated with the frontal executive and visuospatial functions after controlling age, sex, and years of education. Interestingly, the negative relationship between neuroticism and frontal executive function was alleviated in older adults with higher sleep quality. CONCLUSIONS: Our findings demonstrated that higher sleep quality has significant moderating effects on the negative association between neuroticism and frontal executive functions in older adults, which suggests intervention for improving sleep quality such as cognitive behavioral therapy can be considered in older adults who have personality traits associated with a high risk of cognitive impairment.


Assuntos
Função Executiva , Qualidade do Sono , Idoso , Humanos , Testes Neuropsicológicos , Neuroticismo , Personalidade
15.
Sensors (Basel) ; 22(15)2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-35957313

RESUMO

Despite advanced machine learning methods, the implementation of emotion recognition systems based on real-world video content remains challenging. Videos may contain data such as images, audio, and text. However, the application of multimodal models using two or more types of data to real-world video media (CCTV, illegally filmed content, etc.) lacking sound or subtitles is difficult. Although facial expressions in image sequences can be utilized in emotion recognition, the diverse identities of individuals in real-world content limits computational models of relationships between facial expressions. This study proposed a transformation model which employed a video vision transformer to focus on facial expression sequences in videos. It effectively understood and extracted facial expression information from the identities of individuals, instead of fusing multimodal models. The design entailed capture of higher-quality facial expression information through mixed-token embedding facial expression sequences augmented via various methods into a single data representation, and comprised two modules: spatial and temporal encoders. Further, temporal position embedding, focusing on relationships between video frames, was proposed and subsequently applied to the temporal encoder module. The performance of the proposed algorithm was compared with that of conventional methods on two emotion recognition datasets of video content, with results demonstrating its superiority.


Assuntos
Reconhecimento Facial , Algoritmos , Face , Expressão Facial , Humanos , Aprendizado de Máquina
16.
Int J Mol Sci ; 23(4)2022 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-35216180

RESUMO

High mobility group box 1 (HMGB1) is acknowledged to have critical functions; therefore, targeting this protein may have therapeutic effects. One example is potential antiseptic activity obtained by suppressing HMGB1 secretion, leading to the recovery of vascular barrier integrity. Cornuside (CN), which is a product extracted from the fruit of Cornusofficinalis Seib, is a natural bis-iridoid glycoside with the therapeutic effects of suppressing inflammation and regulating immune responses. However, the mechanism of action of CN and impact on sepsis is still unclear. We examined if CN could suppress HMGB1-induced excessive permeability and if the reduction of HMGB1 in response to LPS treatment increased the survival rate in a mouse model of sepsis. In human endothelial cells stimulated by LPS and mice with septic symptoms of cecal ligation and puncture (CLP), we examined levels of proinflammatory proteins and biomarkers as an index of tissue damage, along with decreased vascular permeability. In both LPS-treated human umbilical vein endothelial cells (HUVECs) and the CLP-treated mouse model of sepsis, we applied CN after the induction processes were over. CN suppressed excessive permeability and inhibited HMGB1 release, leading to the amelioration of vascular instability, reduced mortality, and improved histological conditions in the CLP-induced septic mouse model. Overall, we conclude that the suppressed release of HMGB1 and the increased survival rate of mice with CLP-induced sepsis caused by CN may be an effective pharmaceutical treatment for sepsis.


Assuntos
Glucosídeos/farmacologia , Proteína HMGB1/metabolismo , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Piranos/farmacologia , Sepse/tratamento farmacológico , Sepse/metabolismo , Animais , Adesão Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Células Cultivadas , Citocinas/metabolismo , Modelos Animais de Doenças , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Transdução de Sinais/efeitos dos fármacos
17.
Int J Mol Sci ; 23(17)2022 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-36077539

RESUMO

Aging causes a progressive decline in the structure and function of organs. With advancing age, an accumulation of senescent endothelial cells (ECs) contributes to the risk of developing vascular dysfunction and cardiovascular diseases, including hypertension, diabetes, atherosclerosis, and neurodegeneration. Senescent ECs undergo phenotypic changes that alter the pattern of expressed proteins, as well as their morphologies and functions, and have been linked to vascular impairments, such as aortic stiffness, enhanced inflammation, and dysregulated vascular tone. Numerous molecules and pathways, including sirtuins, Klotho, RAAS, IGFBP, NRF2, and mTOR, have been implicated in promoting EC senescence. This review summarizes the molecular players and signaling pathways driving EC senescence and identifies targets with possible therapeutic value in age-related vascular diseases.


Assuntos
Aterosclerose , Células Endoteliais , Envelhecimento/metabolismo , Aterosclerose/metabolismo , Senescência Celular , Células Endoteliais/metabolismo , Endotélio Vascular/metabolismo , Humanos
18.
Int J Mol Sci ; 23(18)2022 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-36142124

RESUMO

Sparstolonin B (SsnB), which is found in Sparganium stoloniferum, prevents the synthesis of inflammatory mediators and is related to functional pathways of survival. In this study, we assessed the possible protective functions of SsnB on lipopolysaccharide (LPS)-induced inflammatory responses. We determined the functions of SsnB on controlling heme oxygenase (HO)-1, cyclooxygenase (COX-)2, and inducible nitric oxide synthase (iNOS) in LPS-activated human umbilical vein endothelial cells (HUVECs). Furthermore, the distinct function of SsnB on the expression of iNOS and well-known pro-inflammatory mediators, such as tumor necrosis factor (TNF)-α and interleukin (IL)-1ß, were assessed in the pulmonary histological status of LPS-injected mice. SsnB upregulated the HO-1 production, inhibited luciferase-NF-κB interaction, and lowered COX-2/PGE2 and iNOS/NO, which lead to the reduction of STAT-1 phosphorylation. Moreover, SsnB enhanced the nuclear translocation of Nrf2, elevated the binding activity between Nrf2 and antioxidant response elements (AREs), and weakened IL-1ß expression on LPS-treated HUVECs. SsnB-suppressed iNOS/NO synthesis was restored by the process of the RNAi inhibition of HO-1. In experiment with an LPS-injected animal model, SsnB remarkably decreased the iNOS expression in the pulmonary biostructure and TNF-α level in the bronchoalveolar lavage fluid (BALF). Therefore, these results demonstrate that SsnB is responsible for inflammation ameliorative activity by controlling iNOS through inhibition of both NF-κB expression and p-STAT-1. Therefore, SsnB could be a candidate for promoting novel clinical substances to remedy pathologic inflammation.


Assuntos
Lipopolissacarídeos , NF-kappa B , Animais , Anti-Inflamatórios/uso terapêutico , Ciclo-Oxigenase 2/metabolismo , Dinoprostona/farmacologia , Heme Oxigenase-1/genética , Heme Oxigenase-1/metabolismo , Compostos Heterocíclicos de 4 ou mais Anéis , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Inflamação/patologia , Mediadores da Inflamação/metabolismo , Lipopolissacarídeos/farmacologia , Luciferases/metabolismo , Camundongos , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
19.
Int J Mol Sci ; 23(18)2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-36142743

RESUMO

Sepsis is an uncontrolled response to inflammatory infection and is associated with high levels of mortality and morbidity. Rg4 is a rare ginsenoside mainly found in the leaves of Panax ginseng C. A. Meyer and the major protopanaxatriol-type ginsenoside of black ginseng. In this study, we determined whether Rg4 affects cecal ligation and puncture (CLP)-induced sepsis. Animals were separated into the following six groups: control group, CLP-operated group, CLP plus maslinic acid (MA), and CLP plus Rg4 (5, 10, or 15 mg/kg). Survival rate, body weight changes, inflammatory cytokines, and histological analyses were assessed. Human endothelial cells were activated with the high-mobility group box 1 (HMGB1) protein and Rg4. Cell viability was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Enzyme-linked immunosorbent assay (ELISA) and Western blot analysis were used to assess inflammation and gene expression, respectively. After CLP surgery, the Rg4-administered group exhibited a higher survival rate and body weight compared with the untreated control group. Rg4 treatment reduced cytokine levels, including tumor necrosis factor (TNF)-α and interleukin (IL)-1ß, as well as nitric oxide (NO) levels and renal inflammation. After Rg4 treatment of HMGB1-activated cells, the expressions of toll-like receptor (TLR) 4 and TNF-α were decreased, and the activation of phosphoinositide 3-kinase (PI3K)/AKT signaling increased cell viability. In summary, Rg4 inhibited inflammation and exhibited a protective effect against CLP-induced sepsis, thereby reinforcing cell survival against septic responses.


Assuntos
Ginsenosídeos , Proteína HMGB1 , Panax , Sepse , Animais , Peso Corporal , Citocinas/metabolismo , Células Endoteliais/metabolismo , Ginsenosídeos/farmacologia , Ginsenosídeos/uso terapêutico , Proteína HMGB1/genética , Humanos , Inflamação , Ligadura , Óxido Nítrico , Panax/metabolismo , Fosfatidilinositol 3-Quinase , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Punções , Sepse/tratamento farmacológico , Sepse/etiologia , Receptor 4 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa
20.
Int J Mol Sci ; 23(11)2022 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-35682801

RESUMO

The SARS-CoV-2 pandemic has created a global public crisis and heavily affected personal lives, healthcare systems, and global economies. Virus variants are continuously emerging, and, thus, the pandemic has been ongoing for over two years. Vaccines were rapidly developed based on the original SARS-CoV-2 (Wuhan-Hu-1) to build immunity against the coronavirus disease. However, they had a very low effect on the virus' variants due to their low cross-reactivity. In this study, a multivalent SARS-CoV-2 vaccine was developed using ferritin nanocages, which display the spike protein from the Wuhan-Hu-1, B.1.351, or B.1.429 SARS-CoV-2 on their surfaces. We show that the mixture of three SARS-CoV-2 spike-protein-displaying nanocages elicits CD4+ and CD8+ T cells and B-cell immunity successfully in vivo. Furthermore, they generate a more consistent antibody response against the B.1.351 and B.1.429 variants than a monovalent vaccine. This leads us to believe that the proposed ferritin-nanocage-based multivalent vaccine platform will provide strong protection against emerging SARS-CoV-2 variants of concern (VOCs).


Assuntos
COVID-19 , Vacinas Virais , Anticorpos Neutralizantes/genética , Linfócitos T CD8-Positivos , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Ferritinas/genética , Humanos , Imunidade , Mutação , SARS-CoV-2 , Vacinas Combinadas
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA