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1.
Integr Cancer Ther ; 23: 15347354241233544, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38469817

RESUMO

BACKGROUND: In the era of precision medicine, individual temperature sensitivity has been highlighted. This trait has traditionally been used for cold-heat pattern identification to understand the inherent physical characteristics, which are influenced by genetic factors, of an individual. However, genome-wide association studies (GWASs) on this trait are limited. METHODS: Using genotype data from 90 patients with advanced non-small cell lung cancer (NSCLC) and epidermal growth factor receptor mutations, we performed a GWAS to assess the association between single nucleotide polymorphisms (SNPs) and temperature sensitivity, such as cold and heat scores. The score of each participant was evaluated using self-administered questionnaires on common symptoms and a 15-item symptom-based cold-heat pattern identification questionnaire. RESULTS: The GWAS was adjusted for confounding factors, including age and sex, and significant associations were identified for cold and heat scores: SNP rs145814326, located on the intron of SORCS2 at chromosome 4p16.1, had a P-value of 1.86 × 10-7; and SNP rs79297667, located upstream from SEMA4D at chromosome 9q22.2, had a P-value of 8.97 × 10-8. We also found that the genetic variant regulates the expression level of SEMA4D in the main tissues, including the lungs and white blood cells, in NSCLC. CONCLUSIONS: SEMA4D was found to be significantly associated with temperature sensitivity in patients with NSCLC, suggesting an increased expression of SEMA4D in patients with higher heat scores. The potential role of temperature sensitivity as a prognostic or predictive marker of immune response in NSCLC should be further studied.


Assuntos
Antígenos CD , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Semaforinas , Humanos , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/genética , Estudo de Associação Genômica Ampla , Temperatura
2.
Nano Lett ; 24(8): 2574-2580, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38349338

RESUMO

The highly programmable and responsive molecular recognition properties of DNA provide unparalleled opportunities for fabricating dynamic nanostructures capable of structural transformation in response to various external stimuli. However, they typically operate in tightly controlled environments because certain conditions (ionic strength, pH, temperature, etc.) must be met for DNA duplex formation. In this study, we adopted site-specific enzymatic ligation and DNA-based layer-by-layer thin film fabrication to build shape-morphing DNA-linked nanoparticle films operational in a broad range of environments. The ligated films remained intact in unusual conditions such as pure water and high temperature causing dissociation of DNA duplexes and showed predictable and reversible shape morphing in response to various environmental changes and DNA exchange reactions. Furthermore, domain-selective ligation combined with photoinduced interlayer mixing allowed for the fabrication of unusual edge-sealed double-layered films through midlayer etching, which is difficult to realize by other methods.


Assuntos
Nanopartículas , Nanoestruturas , DNA/química , Água , Temperatura
3.
Integr Cancer Ther ; 23: 15347354231226256, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38281123

RESUMO

BACKGROUND: Gastric cancer is a common cause of global mortality, with significant challenges during treatment due to side effects and complications. Traditional herbal medicine (THM) has emerged as a potential adjuvant therapy to enhance cancer treatment by reducing side effects and bolstering the immune response. This study conducted a meta-analysis to assess the efficacy and safety of THM as an adjuvant therapy in post-surgical gastric cancer patients. METHODS: PubMed, Cochrane Library, EMBASE, CNKI, CiNii, KMBASE, KISS, OASIS, RISS, and ScienceON databases were searched from inception through December, 2021. The outcomes considered in this analysis encompassed tumor response, quality of life (QoL), side effects, and tumor markers. Additionally, a frequency analysis of the most commonly used herbs in the included studies was conducted. A total of 36 randomized controlled trials (RCTs) were included, and data were extracted according to study design. The analysis compared groups receiving chemotherapy alone with those receiving both chemotherapy and THM treatment. RESULTS: The group receiving both chemotherapy and THM showed substantial improvement in tumor response compared to the chemotherapy-only control group (RR 1.25, 95% CI [1.09, 1.45]). QoL also significantly increased in the THM-treated group. Most drug adverse reactions displayed statistical significance, except for platelet reduction. Tumor markers CEA, CA19-9, and CA72-4 exhibited significant improvements, but CA125 did not. The 1, 2, and 3-year survival rates improved, with RR values of 1.08 (95% CI [1.02, 1.14]), 1.32 (95% CI [1.19, 1.47]), and 1.42 (95% CI [1.12, 1.79]) respectively. However, some publication bias was indicated. CONCLUSION: THM may offer potential benefits as a complementary approach to post-surgical anticancer therapy in gastric cancer patients. Improved tumor response, quality of life, and survival rates were reported. However, it is important to exercise caution due to the possibility of publication bias, and further research is needed to confirm these findings.Registration:PROSPERO CRD 42022354133.


Assuntos
Neoplasias Gástricas , Humanos , Neoplasias Gástricas/tratamento farmacológico , Medicina Herbária , Quimioterapia Adjuvante , Biomarcadores Tumorais , Extratos Vegetais , Ensaios Clínicos Controlados Aleatórios como Assunto
4.
Nat Cell Biol ; 26(2): 235-249, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38267537

RESUMO

The mechanistic target of rapamycin complex 1 (mTORC1) is a master regulator of cell growth, metabolism and autophagy. Multiple pathways modulate mTORC1 in response to nutrients. Here we describe that nucleus-cytoplasmic shuttling of p300/EP300 regulates mTORC1 activity in response to amino acid or glucose levels. Depletion of these nutrients causes cytoplasm-to-nucleus relocalization of p300 that decreases acetylation of the mTORC1 component raptor, thereby reducing mTORC1 activity and activating autophagy. This is mediated by AMP-activated protein kinase-dependent phosphorylation of p300 at serine 89. Nutrient addition to starved cells results in protein phosphatase 2A-dependent dephosphorylation of nuclear p300, enabling its CRM1-dependent export to the cytoplasm to mediate mTORC1 reactivation. p300 shuttling regulates mTORC1 in most cell types and occurs in response to altered nutrients in diverse mouse tissues. Interestingly, p300 cytoplasm-nucleus shuttling is altered in cells from patients with Hutchinson-Gilford progeria syndrome. p300 mislocalization by the disease-causing protein, progerin, activates mTORC1 and inhibits autophagy, phenotypes that are normalized by modulating p300 shuttling. These results reveal how nutrients regulate mTORC1, a cytoplasmic complex, by shuttling its positive regulator p300 in and out of the nucleus, and how this pathway is misregulated in Hutchinson-Gilford progeria syndrome, causing mTORC1 hyperactivation and defective autophagy.


Assuntos
Progéria , Humanos , Camundongos , Animais , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Progéria/genética , Progéria/metabolismo , Transporte Ativo do Núcleo Celular , Proteína Regulatória Associada a mTOR/metabolismo , Aminoácidos/metabolismo , Lamina Tipo A/genética , Lamina Tipo A/metabolismo
5.
ACS Appl Mater Interfaces ; 15(50): 58092-58102, 2023 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-38060278

RESUMO

We synthesized a series of [(l-Ala)x-co-(l-Thr succinate)y] (PATs), which are analogous to natural antifreezing glycoprotein with the structure of [l-Ala-l-Ala-l-Thr disaccharide]n, by varying the composition and degree of succinylation while fixing their molecular weight (Mn) and Ala/Thr ratio at approximately 10-12 kDa and 2:1, respectively. We investigated their ice recrystallization inhibition (IRI), ice nucleation inhibition (INI), dynamic ice shaping (DIS), thermal hysteresis (TH), and protein cryopreservation activities. Both IRI and INI activities were greater for PATs with higher l-Ala content (PATs-3 and PATs-4) than those with lower l-Ala content (PATs-1 and PATs-2). DIS activity with faceted crystal growth was clearly observed in PATs-2 and PATs-4 with a high degree of succinylation. TH was small with <0.1 °C for all PATs and slightly greater for PATs with a high l-Ala content. Except for PATs-1, the protein (lactate dehydrogenase, LDH) stabilization activity was excellent for all PATs studied, maintaining LDH activity as high as that of fresh LDH even after 15 freeze-thaw cycles. To conclude, the cryo-active biomimetic PATs were synthesized by controlling the l-Ala content and degree of succinylation. Our results showed that PATs with an l-Ala content of 65-70% and degree of succinylation of 12-19% exhibited the cryo-activities of IRI, INI, and DIS, and particularly promising properties for the cryoprotection of LDH protein.


Assuntos
Gelo , Ácido Succínico , Treonina , Biomimética , Crioprotetores/farmacologia , Crioprotetores/química , Succinatos
6.
Mar Drugs ; 21(12)2023 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-38132929

RESUMO

The objective of this study was to investigate the effect of low-molecular-weight fish collagen (valine-glycine-proline-hydroxyproline-glycine-proline-alanine-glycine; LMWCP) on H2O2- or LPS-treated primary chondrocytes and monoiodoacetate (MIA)-induced osteoarthritis rat models. Our findings indicated that LMWCP treatment exhibited protective effects by preventing chondrocyte death and reducing matrix degradation in both H2O2-treated primary chondrocytes and cartilage tissue from MIA-induced osteoarthritis rats. This was achieved by increasing the levels of aggrecan, collagen type I, collagen type II, TIMP-1, and TIMP-3, while simultaneously decreasing catabolic factors such as phosphorylation of Smad, MMP-3, and MMP-13. Additionally, LMWCP treatment effectively suppressed the activation of inflammation and apoptosis pathways in both LPS-treated primary chondrocytes and cartilage tissue from MIA-induced osteoarthritis rats. These results suggest that LMWCP supplementation ameliorates the progression of osteoarthritis through its direct impact on inflammation and apoptosis in chondrocytes.


Assuntos
Cartilagem Articular , Osteoartrite , Ratos , Animais , Condrócitos , Hidroxiprolina/efeitos adversos , Hidroxiprolina/metabolismo , Glicina/farmacologia , Peróxido de Hidrogênio/farmacologia , Lipopolissacarídeos/farmacologia , Osteoartrite/induzido quimicamente , Osteoartrite/tratamento farmacológico , Osteoartrite/prevenção & controle , Inflamação/metabolismo , Colágeno Tipo II/farmacologia , Peptídeos/farmacologia , Valina/efeitos adversos , Valina/metabolismo , Células Cultivadas
7.
Artigo em Inglês | MEDLINE | ID: mdl-37903335

RESUMO

Dynamic colors that respond to environmental changes are of great interest for diverse areas of science and technology ranging from chemical and biological sensors to smart information display. Here, we demonstrate a multitude of responsive colors from a conjugated polymer film arising from a thin-film interference. This mechanism provides an excellent control over the thin-film color by varying the film thickness, type of substrate, and degree of polaron population and is generally applicable to various conjugated polymers for further color variation. Furthermore, multiple sets of responsive colors are achieved from a single polymer layer by patterning the underlying substrate to spatially modify the interference conditions. Using this system, we demonstrate the reversible color changes induced by an oxidative or reductive environment with color responsivity controllable with the nature of the polaron state.

8.
Integr Cancer Ther ; 22: 15347354231154267, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37615075

RESUMO

A 4-year prospective cohort study on patients with lung, gastric, hepatic, colorectal, breast, uterine, and ovarian cancer was conducted at the East-West Cancer Center (EWCC) of Daejeon Korean Medicine Hospital in Daejeon, Korea. We divided patients into 2 groups based on how long they had been receiving TKM oncotherapy and compared event-free survival (EFS), telomere length change, and quality of life (QoL). The study collected data on 83 patients from October 2016 to June 2020 and discovered no statistical differences in EFS based on the duration of TKM oncotherapy. In the analysis of changes in QoL outcomes, there were no statistically significant group differences between the groups. After controlling for covariates that could affect telomere length, the long-term TKM oncotherapy group had a higher daily telomere attrition rate. The study of the relationship between telomere length and prognostic factors discovered that patients with advanced N stage at the time of diagnosis and who had previously received radiotherapy had shorter telomere length. When examining associations between SNP genotype and percentile score of telomere length, this study was able to confirm an association between telomere length and rs4387287. This study is significant because it is the first to assess the effects of TKM oncotherapy and investigate telomere length-related factors. To assess the effects of TKM oncotherapy on cancer patients' survival and QoL, a longer-term observational study with a larger sample size is required.


Assuntos
Medicina Tradicional Coreana , Qualidade de Vida , Feminino , Humanos , Estudos Prospectivos , Intervalo Livre de Progressão , Telômero/genética , República da Coreia
9.
ACS Macro Lett ; 12(7): 986-992, 2023 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-37399507

RESUMO

Herein, we report the directional stimuli-responsive self-assembly of gold nanoparticles (AuNPs) coated with a thermoresponsive block copolymer (BCP), poly(ethylene glycol)-b-poly(N-isopropylacrylamide) (PEG-b-PNIPAM) and charged small molecules. AuNPs modified with PEG-b-PNIPAM possessing a AuNP/PNIPAM/PEG core/active/shell structure undergo temperature-induced self-assembly into one-dimensional (1D) or two-dimensional (2D) structures in salt solutions, with the morphology varying with the ionic strength of the medium. Salt-free self-assembly is also realized by modulating the surface charge by the codeposition of positively charged small molecules; 1D or 2D assemblies are formed depending on the ratio between the small molecule and PEG-b-PNIPAM, consistent with the trend observed with the bulk salt concentration. A series of charge-controlled self-assembly at various conditions revealed that the temperature-induced BCP-mediated self-assembly reported here provides an effective means for on-demand directional self-assembly of nanoparticles (NPs) with controlled morphology, interparticle distance, and optical properties, and the fixation of high-temperature structures.

10.
Obes Res Clin Pract ; 17(4): 366-368, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37263852

RESUMO

The relationship between central obesity and depression remains of debate. From the 2019 Korea National Health and Nutrition Examination Survey, data of 3768 adults with available information on neck circumference and depressive mood were analyzed. Multivariate logistic analysis revealed that a small neck circumference was significantly associated with depressive mood among men, but not among women. Our findings indicate that assessing neck circumference among men would help detect depression early.


Assuntos
Depressão , Obesidade , Masculino , Adulto , Humanos , Feminino , Inquéritos Nutricionais , Estudos Transversais , República da Coreia/epidemiologia , Circunferência da Cintura
11.
J Microbiol Biotechnol ; 33(7): 934-940, 2023 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-37100760

RESUMO

Syneilesis palmata (SP) is a traditional medicinal plant. SP has been reported to have anti-inflammatory, anticancer, and anti-human immunodeficiency virus (HIV) activities. However, there is currently no research available on the immunostimulatory activity of SP. Therefore, in this study, we report that S. palmata leaves (SPL) activate macrophages. Increased secretion of both immunostimulatory mediators and phagocytic activity was observed in SPL-treated RAW264.7 cells. However, this effect was reversed by the inhibition of TLR2/4. In addition, inhibition of p38 decreased the secretion of immunostimulatory mediators induced by SPL, and inhibition of TLR2/4 decreased the phosphorylation of p38 induced by SPL. SPL augmented p62/SQSTM1 and LC3-II expression. The increase in protein levels of p62/SQSTM1 and LC3-II induced by SPL was decreased by the inhibition of TLR2/4. The results obtained from this study suggest that SPL activates macrophages via TLR2/4-dependent p38 activation and induces autophagy in macrophages via TLR2/4 stimulation.


Assuntos
Ativação de Macrófagos , Receptor 2 Toll-Like , Animais , Camundongos , Receptor 2 Toll-Like/metabolismo , Proteína Sequestossoma-1/metabolismo , Macrófagos , Células RAW 264.7 , Autofagia , Folhas de Planta/metabolismo
12.
Biomacromolecules ; 24(5): 2118-2126, 2023 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-37040187

RESUMO

Oligonucleotides of adenine (A20), guanine (G20), cytosine (C20), thymine (T20), cytosine-guanine ((CG)20), and adenine-thymine ((AT)20) were investigated as model compounds for ice recrystallization inhibition (IRI). Dehydroxy uracil (dU20), U20, and T20 were also compared to investigate the effect of minute changes in the hydrophobicity of the oligonucleotides on the IRI activity. Among the oligonucleotides considered in this study, T20 exhibited the best performance for IRI. In addition, the degree of polymerization of oligothymines varied over 5, 10, 20, 30, 50, and 100, and T20 was found to be the most effective for IRI. The IRI mechanism was investigated by comparing U20 and T20, which exhibited the lowest and highest IRI activity, respectively, among the oligonucleotides for their dynamic ice-shaping, thermal hysteresis, and ice nucleation inhibition. Little or no dynamic ice-shaping activity and small thermal hysteresis were observed for both nucleotides. All of the findings suggest that not the ice-polymer adhesion but the hydrophobic interactions of T20 in the interface layer might interfere with the water deposition on the ice crystal surfaces and contribute to the IRI activity of the T20 oligonucleotide.


Assuntos
Gelo , Oligonucleotídeos , Timina , Cristalização , Água , Proteínas Anticongelantes/química
13.
ACS Macro Lett ; 12(3): 382-388, 2023 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-36866815

RESUMO

Here, we report charge-transfer-driven self-assembly of conjugated block copolymers (BCP) into highly doped conjugated polymer nanofibers. The ground-state integer charge transfer (ICT) between a BCP composed of poly(3-hexylthiophene) and poly(ethylene oxide) (P3HT-b-PEO) and electron-deficient 2,3,5,6-tetrafluoro-7,7,8,8-tetracyanoquinodimethane (F4TCNQ) induced spontaneous self-assembly of the donor and the acceptor into well-defined one-dimensional nanofibers. The presence of the PEO block plays an important role for the self-assembly by providing a polar environment that can stabilize nanoscale charge transfer (CT) assemblies. The doped nanofibers were responsive to various external stimuli such as heat, chemical, and light and exhibited efficient photothermal properties in the near-IR region. The CT-driven BCP self-assembly reported here provides a new platform for the fabrication of highly doped semiconductor nanostructures.

14.
Epidemiol Health ; 45: e2023021, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36791793

RESUMO

OBJECTIVES: This study aimed to evaluate changes in the cancer treatment rate among patients newly diagnosed with stage IV cancer using socio-demographic and clinical subgroups in a nationwide cohort of Korean patients. METHODS: This retrospective, national-level study used the Korea Central Cancer Registry (KCCR), which is linked to the National Health Insurance Service (NHIS) database, from January 1, 2012 to December 31, 2017. The records of patients newly diagnosed with stage IV of the 5 cancers with the highest cancer-related mortality rate were identified to analyze changes in the treatment rate. The main outcome examined in this study was the change in the cancer treatment rate between 2012 and 2017, as measured using the annual percent change (APC). RESULTS: A total of 106,082 patients with newly diagnosed gastric, colorectal, liver, pancreatic, and lung cancers at the end of life (EoL) were identified from the KCCR-NHIS database. Of these patients, 76,533 (72.1%) received cancer treatment. Over the study period (2012-2017), the proportion of patients who received cancer treatment at EoL decreased by 8.3%, with an APC of -2.1% (95% confidence interval, -2.6 to -1.6). This declining trend of cancer treatment among patients with advanced cancer stage at EoL was consistent among socio-demographic and clinical subgroups. CONCLUSIONS: The proportion of untreated patients with stage IV cancer is increasing in the Korea. For patients who are not undergoing standard cancer treatment near EoL, an alternative care plan, such as early palliative care, should be considered.


Assuntos
Neoplasias Pulmonares , Neoplasias , Humanos , Estudos Retrospectivos , Neoplasias/terapia , Morte , Estadiamento de Neoplasias , República da Coreia/epidemiologia
15.
Nutrients ; 15(2)2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36678190

RESUMO

Flavanones in Citrus unshiu peel (CUP) have been used as therapeutic agents to reduce intestinal inflammation; however, the anti-inflammatory effects of their biometabolites remain ambiguous. Here, we identified aglycone-type flavanones, such as hesperetin and naringenin, which were more abundant in the bioconversion of the CUP than in the ethanol extracts of the CUP. We found that the bioconversion of the CUP induced the canonical nuclear factor-κB pathway via degradation of IκB in Caco-2 cells. To check the immune suppressive capacity of the aglycones of the CUP in vivo, we orally administered the bioconversion of the CUP (500 mg/kg) to mice for two weeks prior to the 3% dextran sulfate sodium treatment. The CUP-pretreated group showed improved body weight loss, colon length shortage, and intestinal inflammation than the control mice. We also found a significant decrease in the population of lamina propria Th17 cells in the CUP-pretreated group following dextran sodium sulfate (DSS) treatment and an increase in mRNA levels of occludin in CUP-treated Caco-2 cells. Pyrosequencing analysis revealed a decreased abundance of Alistipes putredinis and an increased abundance of Muribaculum intestinale in the feces of the CUP-pretreated mice compared to those of the control mice. Overall, these findings suggest that the pre-administration of CUP biometabolites may inhibit the development of murine colitis by modulating intestinal permeability and the gut microbiome.


Assuntos
Citrus , Colite , Flavanonas , Humanos , Camundongos , Animais , Células CACO-2 , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colo/metabolismo , Inflamação/metabolismo , Bactérias , Flavanonas/metabolismo , Permeabilidade , Sulfato de Dextrana/farmacologia , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças
16.
Crit Rev Oncol Hematol ; 181: 103898, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36535489

RESUMO

Aromatase inhibitor-induced arthralgia (AIA) contributes to poor adherence of aromatase inhibitor therapies in patients with breast cancer. A systematic review using network meta-analysis (NMA) was conducted to examine the clinical effectiveness of multiple therapies and rank probabilities for the management of AIA. Randomized controlled trials (RCTs) assessing treatments for AIA in postmenopausal women with stage 0-III hormone receptor-positive breast cancer were searched from inception to October 2021. The main NMA involved 1516 participants from 17 RCTs. Acupuncture was the highest ranked intervention to improve pain intensity followed by sham acupuncture, multicomponent herbal medicine, exercise, duloxetine, vitamin D, omega-3 fatty acids, physical therapy, testosterone, and inactive controls. Single natural products were inferior to controls. The current review provides new insights into the management of AIA in breast cancer survivors for increased survival and can be utilized to make evidence-based decisions regarding treatment.


Assuntos
Inibidores da Aromatase , Neoplasias da Mama , Feminino , Humanos , Inibidores da Aromatase/efeitos adversos , Metanálise em Rede , Artralgia/induzido quimicamente , Artralgia/terapia , Resultado do Tratamento , Neoplasias da Mama/complicações , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/induzido quimicamente
17.
Autophagy ; 19(3): 943-944, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-35822241

RESUMO

Impaired autophagosome formation and reduced flux through the macroautophagy/autophagy pathway occurs outside the brain as part of normal aging in various species. We recently identified autophagic decline in mouse brain tissue dependent on aging. This sits alongside significantly increased expression of the Sorbs3/SORBS3/vinexin (sorbin and SH3 domain containing 3) gene in older mouse and human brains. We found that SORBS3 negatively regulates autophagy in several cell lines, including mouse primary neurons. SORBS3 depletion increases F-actin structures, which compete with YAP1-WWTR1/TAZ to bind AMOT (angiomotin) proteins in the cytosol. Unbound YAP1-WWTR1/TAZ is free to move into the nucleus and upregulate YAP1-WWTR1/TAZ target gene expression. This upregulates autophagosome formation, in part through increased expression of myosin- and actin-related genes. Moreover, we have shown these YAP1-WWTR1/TAZ target genes are downregulated in older mouse and human brains. Taken together, our findings suggest that increased SORBS3 expression contributes to autophagic decline in normal brain aging across species.


Assuntos
Autofagia , Transativadores , Animais , Humanos , Camundongos , Transativadores/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Envelhecimento , Encéfalo/metabolismo , Proteínas com Motivo de Ligação a PDZ com Coativador Transcricional , Proteínas Adaptadoras de Transdução de Sinal/metabolismo
18.
Phytother Res ; 37(2): 452-463, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36122906

RESUMO

To target benign prostatic hyperplasia (BPH) as a common urinary disease in old men, in the current study, the antiproliferative and apoptotic mechanism of SH-PRO, a mixture of Angelica gigas and Astragalus membranaceus (2:1), was evaluated in BPH-1 cells and rats with testosterone-induced BPH. Herein, SH-PRO significantly reduced the viability of BPH-1 cells and dihydrotestosterone (DHT)-treated RWPE-1 cells. Also, SH-PRO increased the sub-G1 population in BPH-1 cells and consistently attenuated the expression of pro-PARP, pro-caspase 3, Bcl2, FOXO3a, androgen receptor (AR), and prostate-specific antigen (PSA) in BPH-1 cells and DHT-treated RWPE-1 cells. Of note, SH-PRO generated reactive oxygen species (ROS) in BPH-1 cells, while ROS inhibitor N-acetyl-l-cysteine (NAC) disturbed the ability of SH-PRO to reduce the expression of pro-PARP, FOXO3a, catalase, SOD, and increase sub-G1 population in BPH-1 cells. Furthermore, oral treatment of SH-PRO significantly abrogated the weight of the prostate in testosterone-treated rats compared to BPH control with the reduced expression of AR, PSA, and DHT and lower plasma levels of DTH, bFGF, and EGF with no toxicity. Overall, these findings highlight the antiproliferative and apoptotic potential of SH-PRO via ROS-mediated activation of PARP and caspase 3 and inhibition of FOXO3a/AR/PSA signaling as a potent anti-BPH candidate.


Assuntos
Hiperplasia Prostática , Masculino , Humanos , Ratos , Animais , Hiperplasia Prostática/tratamento farmacológico , Hiperplasia Prostática/induzido quimicamente , Antígeno Prostático Específico , Espécies Reativas de Oxigênio/efeitos adversos , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Receptores Androgênicos/metabolismo , Caspases , Caspase 3 , Extratos Vegetais/uso terapêutico , Testosterona/efeitos adversos
19.
Integr Cancer Ther ; 21: 15347354221144311, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36565160

RESUMO

In epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC), acquired resistance to EGFR tyrosine kinase inhibitors (TKI) leads to disease progression. Strategies to overcome the resistance are required in treatment for advanced lung cancer. In this study, we investigated the therapeutic effect of afatinib and HangAmDan-B1 (HAD-B1) co-administration in gefitinib-resistant NSCLC using HCC827-GR, NSCLC cell line with gefitinib resistance, and the HCC827-GR cell implanted mouse model. HAD-B1 consists of 4 herbs, Panax notoginseng Radix, Cordyceps militaris, Panax ginseng C. A. Mey, and Boswellia carteri Birdwood, and has been reported to be effective in patients with advanced lung cancer in clinical practice. Our findings demonstrated that HAD-B1 combined with afatinib markedly inhibited cell proliferation and induced apoptosis compared to afatinib monotherapy and HAD-B1 monotherapy. Inhibition of HCC827-GR cell proliferation by HAD-B1 occurred through MET amplification and reduced phosphorylation, and the synergistic effect of afatinib and HAD-B1 induced cell cycle arrest and apoptosis in HCC827-GR cells via the downregulation of ERK and mTOR signaling pathways. In hematology and biochemistry tests, HAD-B1 alleviated the toxicity of tumor. In conclusion, HAD-B1 combined with afatinib would be a promising therapeutic strategy for NSCLC with EGFR-TKI resistance.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Animais , Camundongos , Carcinoma Pulmonar de Células não Pequenas/patologia , Afatinib/farmacologia , Gefitinibe/farmacologia , Gefitinibe/uso terapêutico , Neoplasias Pulmonares/metabolismo , Quinazolinas/farmacologia , Quinazolinas/uso terapêutico , Receptores ErbB/metabolismo , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos , Mutação
20.
Korean J Women Health Nurs ; 28(2): 145-153, 2022 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-36312860

RESUMO

Purpose: This study aimed to investigate the influencing factors of breast cancer recurrence by comparing the risk factors and lifestyle patterns related to breast cancer in Korean women with and without recurrence. Methods: This cross-sectional survey comprised 241 Korean women diagnosed with breast cancer who had received follow-up treatment. Participants were recruited from a university hospital in Seoul and an online social media platform for breast cancer patients. Data were collected either via online or a paper survey, using a structured questionnaire that included general and disease-related characteristics and lifestyle behaviors. Data were analyzed using descriptive statistics, univariate analysis, and logistic regression. Results: Recurrence of breast cancer was influenced by four factors; childbirth experience, consumption of green/yellow vegetables, drinking behavior, and recovery from fatigue after sleep.Prevalence of recurrent breast cancer was associated with no childbirth experience (OR=2.29, p=.010), fewer green/yellow vegetables (OR=0.71, p=.008), drinking behavior (OR=0.24, p=.001), and a lower level of recovery from fatigue after sleep (OR=0.51, p<.001). Conclusion: Aside from having experienced childbirth, this study identified several modifiable factors that influence breast cancer recurrence. Increasing green/yellow vegetable intake, alleviating fatigue, and reducing alcohol intake are important. Intervention strategies in clinical research and practice can be applied to address risk factors and reduce the prevalence of recurrent breast cancer.

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