RESUMO
Challenges in directed differentiation and survival limit the clinical use of stem cells despite their promising therapeutic potential in regenerative medicine. Nanotechnology has emerged as a powerful tool to address these challenges and enable precise control over stem cell fate. In particular, nanomaterials can mimic an extracellular matrix and provide specific cues to guide stem cell differentiation and proliferation in the field of nanotechnology. For instance, recent studies have demonstrated that nanostructured surfaces and scaffolds can enhance stem cell lineage commitment modulated by intracellular regulation and external stimulation, such as reactive oxygen species (ROS) scavenging, autophagy, or electrical stimulation. Furthermore, nanoframework-based and upconversion nanoparticles can be used to deliver bioactive molecules, growth factors, and genetic materials to facilitate stem cell differentiation and tissue regeneration. The increasing use of nanostructures in stem cell research has led to the development of new therapeutic approaches. Therefore, this review provides an overview of recent advances in nanomaterials for modulating stem cell differentiation, including metal-, carbon-, and peptide-based strategies. In addition, we highlight the potential of these nano-enabled technologies for clinical applications of stem cell therapy by focusing on improving the differentiation efficiency and therapeutics. We believe that this review will inspire researchers to intensify their efforts and deepen their understanding, thereby accelerating the development of stem cell differentiation modulation, therapeutic applications in the pharmaceutical industry, and stem cell therapeutics.
Assuntos
Diferenciação Celular , Nanoestruturas , Células-Tronco , Humanos , Células-Tronco/citologia , Medicina Regenerativa , Animais , NanotecnologiaRESUMO
OBJECTIVE: To assess whether bioimpedance spectroscopy analysis (BIA) can be used as a tool to guide postoperative fluid management in patients undergoing cardiac surgery. DESIGN: An observational study. SETTING: A single tertiary hospital. PARTICIPANTS: Patients who underwent cardiac surgery with cardiopulmonary bypass between June and November 2023 who were able to undergo BIA measurements. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Correlations between BIA measurements of extracellular fluid (ECF) and total body water (TBW) volumes and daily changes in weight and 24-hour net intake and output (I/O) of fluids were assessed. Correlations between predischarge ECF volume as a percentage of TBW volume (ECF%TBW) and predischarge pro-B-type natriuretic peptide (Pro-BNP) levels and readmissions were analyzed. Changes in daily ECF volume significantly correlated with daily weight changes (p < 0.01) and 24-hour I/O (p < 0 .01). TBW volume significantly correlated with daily weight changes (p < 0.01) and with 24-hour I/O (p = 0.04). Daily weight changes did not correlate with 24-hour I/O (p = 0.06). The patients with predischarge ECF%TBW(%) greater than or equal to 51 had significantly higher predischarge Pro-BNP than those with ECF%TBW(%) less than 51 (p < 0.01). Patients who had heart failure revisits or admissions after discharge had a higher predischarge ECF%TBW(%) on index admission compared with patients who did not have heart failure readmissions (p = 0.01). CONCLUSIONS: BIA measurements in postoperative cardiac surgery patients may be a valuable tool to quantitatively determine fluid status to help guide fluid management in this patient population. Further studies validating the use of BIA for postoperative care in this population are warranted.
RESUMO
OBJECTIVES: To compare the outcomes of factor eight inhibitor bypassing activity (FEIBA) versus fresh frozen plasma (FFP) as the primary treatment for postoperative coagulopathy in patients undergoing cardiac surgery. DESIGN: A retrospective, propensity-matched study. SETTING: A single, tertiary hospital. PARTICIPANTS: Patients who underwent noncoronary cardiac surgery with cardiopulmonary bypass between 2015 and 2023. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We stratified patients into 2 groups based on whether they received intraoperative FFP or FEIBA; cases using both were excluded. We analyzed 434 cases, with 197 receiving FFP and 237 receiving FEIBA. After propensity matching, there was no significant difference in the proportion of the patients who required packed red blood cell transfusions (p = 0.08). However, of those who required packed red blood cell transfusions, patients in the FEIBA group required significantly fewer units of packed red blood cells (p < 0.001). Significantly fewer patients in the FEIBA group required platelet (p < 0.001) and cryoprecipitate (p < 0.001) transfusions. The FEIBA group showed decreased prolonged postoperative intubation (p = 0.05), decreased intensive care unit length of stay (p = 0.04), and lower 30-day readmission rates (p = 0.03). There were no differences in the rates of thrombotic complications between the 2 cohorts. CONCLUSIONS: In the initial treatment of postcardiopulmonary bypass coagulopathy, FEIBA may be more effective than FFP in decreasing blood product transfusions and readmission rates. Further studies are needed to explore the potential routine use of FEIBA as first-line agent in this patient population.
Assuntos
Transtornos da Coagulação Sanguínea , Fatores de Coagulação Sanguínea , Procedimentos Cirúrgicos Cardíacos , Humanos , Estudos Retrospectivos , Masculino , Feminino , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Pessoa de Meia-Idade , Idoso , Transtornos da Coagulação Sanguínea/etiologia , Transtornos da Coagulação Sanguínea/terapia , Fatores de Coagulação Sanguínea/uso terapêutico , Plasma , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Pontuação de PropensãoRESUMO
Cysteine-rich angiogenic inducer 61 (CYR61) is a protein from the CCN family of matricellular proteins that play diverse regulatory roles in the extracellular matrix. CYR61 is involved in cell adhesion, migration, proliferation, differentiation, apoptosis, and senescence. Here, we show that CYR61 induces chemoresistance in triple-negative breast cancer (TNBC). We observed that CYR61 is overexpressed in TNBC patients, and CYR61 expression correlates negatively with the survival of patients who receive chemotherapy. CYR61 knockdown reduced cell migration, sphere formation and the cancer stem cell (CSC) population and increased the chemosensitivity of TNBC cells. Mechanistically, CYR61 activated Wnt/ß-catenin signaling and increased survivin expression, which are associated with chemoresistance, the epithelial-mesenchymal transition, and CSC-like phenotypes. Altogether, our study demonstrates a novel function of CYR61 in chemotherapy resistance in breast cancer.
Assuntos
Proteína Rica em Cisteína 61 , Resistencia a Medicamentos Antineoplásicos , Transição Epitelial-Mesenquimal , Regulação Neoplásica da Expressão Gênica , Survivina , Neoplasias de Mama Triplo Negativas , Humanos , Proteína Rica em Cisteína 61/genética , Proteína Rica em Cisteína 61/metabolismo , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/metabolismo , Survivina/metabolismo , Survivina/genética , Feminino , Resistencia a Medicamentos Antineoplásicos/genética , Via de Sinalização Wnt , Movimento Celular , Linhagem Celular Tumoral , Células-Tronco Neoplásicas/patologia , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/efeitos dos fármacos , Regulação para Cima , Proliferação de Células , Apoptose , Animais , CamundongosRESUMO
Platelet-derived growth factor receptor (PDGFR) plays an essential role in the proliferation and invasion of malignant cancer cells. However, the functional role of PDGFR alpha (PDGFRA) in HER2-positive (HER2+) breast cancer has not been fully clarified yet. Thus, the objective of this study was to investigate the clinical significance of PDGFRA and the therapeutic potential of PDGFR inhibitors as part of an effort to overcome trastuzumab (TRZ) resistance. Aberrant PDGFRA expression is closely associated with decreased survival in HER2+ breast cancers. Therefore, we established BT474 trastuzumab-sensitive (TRZ_S) and trastuzumab-resistant (TRZ_R) cells to investigate the association between PDGFR signaling and TRZ resistance. We found that PDGFRA was significantly upregulated in the BT474 TRZ_R cells. In addition, IL-6 expression, which was also found to be upregulated in the TRZ_R cells, was induced by PDGFC, a ligand of PDGFR. Next, we investigated the effects of ponatinib and sunitinib, PDGFR inhibitors, on the BT474 TRZ_R and HCC1954 (TRZ-resistant cell line) cells. These inhibitors decreased cell viability and migration in a dose-dependent manner. Additionally, IL-6 expression was decreased by ponatinib in both the BT474 TRZ_R and HCC1954 cells. In contrast, IL-6 was not suppressed by TRZ, implying that the PDGFRA/STAT3/IL-6 axis is associated with resistance to TRZ. In addition, we found that STAT3 and ERK phosphorylation were increased in the BT474 TRZ_R cells. IL-6 expression was suppressed by a STAT3 inhibitor, indicating that IL-6 expression is modulated downstream of STAT3. Taken together, these results suggest that PDGFRA could serve as a therapeutic target to overcome TRZ resistance.
RESUMO
Cystic echinococcosis (CE) is a representative neglected tropical disease (NTD) with increased morbidity and mortality but is ignored and overlooked in developed countries. Serological and radiographic findings are helpful in distinguishing these parasites; however, conflicting results of these can make it difficult to diagnose if medical knowledge of hepatic parasitic disease, including the etiology, features of imaging, and immunodiagnostic test, is not acquired. We report the case of a male patient with dyspepsia and right epigastric pain who had positive results for cysticercosis antibodies on immunodiagnostic examination. Abdominal ultrasonography revealed two huge communicating cystic lesions measuring 8-11 cm. Further evaluations for cysticercosis of the brain (neurocysticercosis) and eyes (intraocular cysticercosis) were unremarkable throughout the brain imaging test and fundus examination. A laparoscopic right hemi-hepatectomy was performed for diagnosis and treatment. On histopathological examination, diverse stages of Echinococcus granulosus were identified. Albendazole was administered postoperatively, and the patient was also followed up. We should be aware of the etiologies that have been prevalent in parasite infection thought to be the cause of hepatic cysts. Moreover, we make an effort to ascertain the patient's nationality, past travel experiences, and immediate environment, including any animals and pets. We present the case of a patient who was worried about the possibility of liver invasion of cysticercus due to the positivity of the cysticercosis antibody and was ultimately diagnosed with CE.
RESUMO
Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer. TNBC patients typically exhibit unfavorable outcomes due to its rapid growth and metastatic potential. Here, we found overexpression of CCN3 in TNBC patients. We identified that CCN3 knockdown diminished cancer stem cell formation, metastasis, and tumor growth in vitro and in vivo. Mechanistically, ablation of CCN3 reduced activity of the EGFR/MAPK pathway. Transcriptome profiling revealed that CCN3 induces glycoprotein nonmetastatic melanoma protein B (GPNMB) expression, which in turn activates the EGFR pathway. An interrogation of the TCGA dataset further supported the transcriptional regulation of GPNMB by CCN3. Finally, we showed that CCN3 activates Wnt signaling through a ligand-dependent or -independent mechanism, which increases microphthalmia-associated transcription factor (MITF) protein, a transcription factor inducing GPNMB expression. Together, our findings demonstrate the oncogenic role of CCN3 in TNBC, and we propose CCN3 as a putative therapeutic target for TNBC.
Assuntos
Neoplasias de Mama Triplo Negativas , Humanos , Linhagem Celular Tumoral , Proliferação de Células , Receptores ErbB/metabolismo , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Fatores de Transcrição , Neoplasias de Mama Triplo Negativas/patologiaRESUMO
BACKGROUND/AIM: Chemokine (C-C motif) ligand 2 (CCL2) influences growth and metastasis and is associated with poor prognosis in various cancers. However, the regulatory mechanism of CCL2 induction by human epidermal growth factor receptor 2 (HER2) is not fully understood in breast cancer. Thus, we investigated how CCL2 expression is regulated in HER2-positive (HER2+) breast cancer. MATERIALS AND METHODS: A human cytokine array was performed to investigate the differential expression of cytokines by HER2 overexpression. Quantitative reverse transcription PCR, enzyme-linked immunosorbent assay and western blot were performed to detect the levels of mRNA and protein expression. Cell cycle and proliferation were analyzed by flow cytometry. Cell invasion was analyzed by Boyden chamber assay. RESULTS: Our results showed that HER2 overexpression augmented CCL2 expression. Epidermal growth factor receptor (EGFR) and Src activities were increased in the HER2-overexpressed breast cancer cells. Interestingly, HER2-induced CCL2 expression could not be down-regulated by trastuzumab, while neratinib or saracatinib led to a decrease in the expression of CCL2 in HER2+ breast cancer cells. CONCLUSION: CCL2 expression is regulated through the EGFR/Src-dependent signaling in HER2+ breast cancer.
Assuntos
Neoplasias da Mama , Quimiocina CCL2 , Feminino , Humanos , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Quimiocina CCL2/genética , Quimiocina CCL2/metabolismo , Quimiocinas , Citocinas , Receptores ErbB/metabolismo , Receptor ErbB-2 , Quinases da Família src/metabolismoRESUMO
Basal-like breast cancer (BLBC) has a clinically aggressive nature. It is prevalent in young women and is known to often relapse rapidly. To date, the molecular mechanisms regarding the aggressiveness of BLBC have not been fully understood. In the present study, mechanisms of aggressiveness of BLBC involving EGFR and/or HER2 expression and interactions between tumor and tumor-associated macrophages (TAMs) were explored. The prognosis of breast cancer patients who underwent surgery at Samsung Medical Center was analyzed. It was found that the co-expression of EGFR and HER2 was associated with a worse prognosis. Therefore, we generated EGFR-positive BLBC cells with stable HER2 overexpression and analyzed the profile of secretory cytokines. Chemokine (C-C motif) ligand 2 (CCL2) expression was increased in HER2-overexpressed BLBC cells. Recombinant human CCL2 treatment augmented the motility of TAMs. In addition, the conditioned culture media of HER2-overexpressed BLBC cells increased the motility of TAMs. Furthermore, activation of TAMs by CCL2 or the conditioned culture media of HER2-overexpressed cells resulted in the production of pro-inflammatory cytokines, such as IL-8 and IL-1ß. These observations reveal that CCL2 derived from EGFR and HER2 co-expressed BLBC cells can lead to increased TAM recruitment and the induction of IL-8 and IL-1ß from recruited TAMs, triggering the tumorigenesis of breast cancer with the expression of both EGFR and HER2. Our findings demonstrate that EGFR+ and HER2+ BLBC aggressiveness is partially mediated through the interaction between BLBC and TAMs recruited by CCL2.
Assuntos
Neoplasias da Mama , Feminino , Humanos , Neoplasias da Mama/metabolismo , Macrófagos Associados a Tumor/metabolismo , Meios de Cultivo Condicionados , Interleucina-8 , Recidiva Local de Neoplasia , Citocinas , Receptores ErbB/genética , Linhagem Celular TumoralRESUMO
Despite advances in predicting physical peptide-major histocompatibility complex I (pMHC I) binding, it remains challenging to identify functionally immunogenic neoepitopes, especially for MHC II. By using the results of >36,000 immunogenicity assay, we developed a method to identify pMHC whose structural alignment facilitates T cell reaction. Our method predicted neoepitopes for MHC II and MHC I that were responsive to checkpoint blockade when applied to >1,200 samples of various tumor types. To investigate selection by spontaneous immunity at the single epitope level, we analyzed the frequency spectrum of >25 million mutations in >9,000 treatment-naive tumors with >100 immune phenotypes. MHC II immunogenicity specifically lowered variant frequencies in tumors under high immune pressure, particularly with high TCR clonality and MHC II expression. A similar trend was shown for MHC I neoepitopes, but only in particular tissue types. In summary, we report immune selection imposed by MHC II-restricted natural or therapeutic T cell reactivity.
Assuntos
Neoplasias , Humanos , Neoplasias/genética , Neoplasias/terapia , Epitopos/genética , Linfócitos T , Peptídeos/química , Peptídeos/metabolismoRESUMO
Immune checkpoint blockades (ICBs) have revolutionized cancer treatment. Recent studies have revealed a subset of triple-negative breast cancer (TNBC) to be considered as an immunogenic breast cancer subtype. Characteristics of TNBC, such as higher mutation rates and number of tumor-infiltrating immune cells, render the immunogenic phenotypes. Consequently, TNBCs have shown durable responses to ICBs such as atezolizumab and pembrolizumab in clinic. However, a significant number of TNBC patients do not benefit from these therapies, and mechanisms of resistance are poorly understood. Here, we review biomarkers that predict the responsiveness of TNBCs to ICB and recent advances in delineating molecular mechanisms of resistance to ICBs.
RESUMO
The proactive safety seat (PSS) is a recently developed active safety system for securing occupant safety in out-of-seat position (OOSP), which was applied in the Hyundai Genesis G80 in 2020. However, there has not been sufficient quantifiable verification supporting the effectiveness of the PSS. The present study was performed to determine the effectiveness of the PSS for occupant safety in OOSP and to identify areas for additional improvement. Six test conditions were considered to determine the effectiveness of the PSS for augmentation of occupant safety in OOSP. Ten healthy men participated in the tests. Compared with the no PSS condition, maximum head excursion and neck rotation were significantly decreased in the PSS condition by 0.6-0.8-fold and 0.6-0.7-fold, respectively (P < 0.05). The PSS condition in which the seat pan was moved forward to the mid position showed a greater effect in reducing the characteristic motions related to submarining, compared with the condition in which the seat pan was moved rearward to the mid position (P < 0.05). These results suggested that PSS augments occupant safety in OOSP. This study provides valuable insights in ameliorating risks to the occupant in unintended seat positions before braking and/or collision.
Assuntos
Acidentes de Trânsito , Acidentes de Trânsito/prevenção & controle , Fenômenos Biomecânicos , Humanos , MasculinoRESUMO
Calystegia soldanella is a halophyte and a perennial herb that grows on coastal sand dunes worldwide. Extracts from this plant have been previously revealed to have a variety of bioactive properties in humans. However, their effects on colorectal cancer cells remain poorly understood. In the present study, the potential biological activity of C. soldanella extracts in the colorectal cancer cell line HT29 was examined. First, five solvent fractions [nhexane, dichloromethane (DCM), ethyl acetate, nbutanol and water] were obtained from the crude extracts of C. soldanella through an organic solvent extraction method. In particular, the DCM fraction was demonstrated to exert marked dose and timedependent inhibitory effects according to results from the cell viability assay. Data obtained from the apoptosis assay suggested that the inhibition of HT29 cell viability induced by DCM treatment was attributed to increased apoptosis. The apoptotic rate was markedly increased in a dosedependent manner, which was associated with the protein expression levels of apoptosisrelated proteins, including increased Fas, Bad and Bax, and decreased procaspase8, Bcl2, BclxL, procaspase9, procaspase7 and procaspase3. A mitochondrial membrane potential assay demonstrated that more cells became depolarized and the extent of cytochrome c release was markedly increased in a dosedependent manner in HT29 cells treated with DCM. In addition, cell cycle analysis confirmed Sphase arrest following DCM fraction treatment, which was associated with decreased protein expression levels of cell cyclerelated proteins, such as cyclin A, CDK2, cell division cycle 25 A and cyclin dependent kinase inhibitor 1. Based on these results, the present study suggested that the DCM fraction of the C. soldanella extract can inhibit HT29 cell viability whilst inducing apoptosis through mitochondrial membrane potential regulation and Sphase arrest. These results also suggested that the DCM fraction has potential anticancer activity in HT29 colorectal cells. Further research on the composition of the DCM fraction is warranted.
Assuntos
Proteínas Reguladoras de Apoptose/metabolismo , Calystegia/química , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Extratos Vegetais/farmacologia , Pontos de Checagem da Fase S do Ciclo Celular/efeitos dos fármacos , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Neoplasias Colorretais , Citocromos c/metabolismo , Relação Dose-Resposta a Droga , Células HT29 , Humanos , Cloreto de Metileno/químicaRESUMO
A complete hydrodeoxygenation(HDO) of vanillin to yield cycloalkanes was performed using bifunctional Ru loaded HZSM-5 catalysts with different metal loadings (0.1, 0.5, 1, 3, and 5 wt%) and Si/Al2 ratios (Si/Al2 = 23,300) in n-octane/water biphasic system. Both the reaction pathway and product distribution were influenced by the metal/acid balance of the catalysts. Higher metal/acid ratio promoted Caryl-C cleavage reaction, resulting in the increased yield of cyclohexane. Synergetic effect of metal and acid sites was observed in the bifunctional catalyst, attaining as high as 40-fold increase of metal efficiency in the ring hydrogenation reaction, compared to lone metal site catalyst. The effect of solvent composition was evaluated, revealing that the presence of water promoted the overall HDO reaction. By balancing metal/acid and introducing appropriate solvent system, efficient catalytic system that minimized carbon loss and improved metal efficiency for vanillin HDO was obtained.
Assuntos
Óleos de Plantas , Polifenóis , Benzaldeídos , CatáliseRESUMO
The seat comfort of automobiles is one of the significant factors for determining the driver's fatigue, emotional experience, and individual space (which captures their individuality, rather than just a means of transportation in modern society). Conventional automobile seats could not provide seating comfort suitable for all drivers, in the form of seats that fit each driver's body type and the difficulty of meeting individual needs. This study proposes self-shape adjustable (the SSA seats) seats that improve the sitting comfort, safety, and secure the stability, by adjusting shape fit to the driver's body type. The SSA seats transforms the seat itself, in a way that improves the distribution of contact pressure and reduces sitting fatigue, with the pneumatic system. The transformed seats provide better sitting comfort and safety than the conventional automobile seat, by providing a seat shape suitable for the body shape of all users. It was verified that the SSA seats, proposed in this paper, have a uniform and improved pressure distribution, compared to the conventional seat, in various sitting postures; the contact area between the seat and user is enlarged, and the pressure concentrated on the ischial bone is lowered. In addition, it was proven (through user evaluation) that quantitative evaluation verification was the same as qualitative evaluation results.
Assuntos
Ergonomia , Postura Sentada , Automóveis , Desenho de Equipamento , PosturaRESUMO
To develop a wrist robotic exoskeleton-type interface (REI) for force interaction, it should have a suitable range of motion similar to human wrist activities of daily living, large torque output performance, and low moving parts inertia for dynamic motion response to cover the human behavior frequency. In this paper, a wrist REI based on a fully actuated coaxial spherical parallel mechanism (CSPM) is proposed to satisfy the aforementioned features. The fully actuated CSPM-based wrist REI (FC-WREI) has the characteristics of pure rotation similar to the human wrist, high torque output by parallel torque synthesis, and low moving parts inertia due to the base arrangement of the actuators. Due to the mechanical advantages and design optimization, the FC-WREI maximally provides torque as much as 56.49-130.43% of the maximum isometric torque of the human wrist, while providing a consistent range of motion to the human wrist without interference problem. Moreover, it is confirmed that the inertia of the FC-WREI is up to 5.35 times lower than similar devices. These advantages of the FC-WREI mean that the device is applicable to various fields of REIs for force interaction.
Assuntos
Exoesqueleto Energizado , Punho , Atividades Cotidianas , Fenômenos Biomecânicos , Humanos , Torque , Articulação do PunhoRESUMO
Particulate matter has been increasing worldwide causing air pollution and serious health hazards. Owing to increased time spent indoors and lifestyle changes, assessing indoor air quality has become crucial. This study investigated the effect of watering and drought and illumination conditions (constant light, light/dark cycle, and constant dark) on particulate matter2.5 (PM2.5) removal and surface characterization of leaf in a botanical plant-based biofilter system. Using Ardisia japonica and Hedera helix as experimental plants in the plant-based biofilter system, PM2.5, volatile organic carbon, and CO2, as the evaluators of indoor air quality, were estimated using a sensor. Morphological and chemical changes of the leaf surface (i.e., roughness and wax) associated with PM2.5 removal were characterized via scanning electron microscopy, Fourier transform infrared spectroscopy, and atomic force microscopy. The highest PM2.5 removal efficiency, stomata closure, high leaf roughness, and wax layer were observed under drought with constant light condition. Consequently, PM2.5 removal was attributed to the combined effect of leaf roughness and wax by adsorption rather than stomatal uptake. These results suggest that operating conditions of indoor plant-based biofilter system such as watering (or drought) and illumination may be applied as a potential strategy for enhancing PM2.5 removal.
RESUMO
Plant polyphenols are widely used to treat various inflammatory diseases, owing to their ability to suppress reactive oxygen species production and the expression of inflammatory cytokines. Herein, we investigated phenolic compounds from Calystegia soldanella using UPLC Q-TOF MS/MS and their antioxidative and anti-inflammatory activities were analyzed. The C. soldanella ethyl acetate fraction (CsEF) had the strongest antioxidative activity, given its high polyphenol compound content. It also exhibited anti-inflammatory effects, inhibiting the production of inflammatory cytokines such as NO, PGE2, IL-1ß, IL-6, and TNF-α in LPS-stimulated mouse macrophages. CsEF activated the nuclear transcription factor Nrf-2, thereby upregulating antioxidant enzymes such as HO-1 and NQO-1 and inhibiting NF-κB expression, which in turn, suppressed the expression of COX-2, iNOS, and inflammatory cytokines, ultimately exerting anti-inflammatory effects. Further, UPLC-Q-TOF-MS/MS was used to analyze the polyphenol compound contents in CsEF. The quercetin glycosides isoquercitrin and quercitrin were the primary flavonoid compounds, while the caffeic acid derivatives, chlorogenic acid and dicaffeoylquinic acid, were the primary phenolic acids. Thus, C. soldanella, which had only a limited use thus far as a medicinal plant, may serve as a natural medicinal resource for treating inflammatory diseases.
RESUMO
About 70% of breast cancers overexpress estrogen receptor α (ERα, encoded by ESR1). Tamoxifen, a competitive inhibitor of estrogen that binds to ER, has been widely used as a treatment for ER-positive breast cancer. However, 20-30% of breast cancer is resistant to tamoxifen treatment. The mechanisms underlying tamoxifen resistance remain elusive. We found that Yes-associated protein (YAP; also known as YAP1), connective tissue growth factor (CTGF; also known as CCN2) and cysteine-rich angiogenic inducer 61 (Cyr61; also known as CCN1) are overexpressed, while ERα is downregulated in tamoxifen-resistant breast cancer. Inhibition of YAP, CTGF and Cyr61 restored ERα expression and increased sensitivity to tamoxifen. Overexpression of YAP, CTGF, and Cyr61 led to downregulation of ERα and conferred resistance to tamoxifen in ER-positive breast cancer cells. Mechanistically, CTGF and Cyr61 downregulated ERα expression at the transcriptional level by directly binding to the regulatory regions of the ERα-encoding gene, leading to increased tamoxifen resistance. Also, CTGF induced Glut3 (also known as SLC2A3) expression, leading to increased glycolysis, which enhanced cell proliferation and migration in tamoxifen-resistant cells. Together, these results demonstrate a novel role of YAP, CTGF and Cyr61 in tamoxifen resistance and provide a molecular basis for their function in tamoxifen-resistant breast cancer.
Assuntos
Neoplasias da Mama , Tamoxifeno , Proteínas Adaptadoras de Transdução de Sinal , Mama/metabolismo , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Linhagem Celular Tumoral , Fator de Crescimento do Tecido Conjuntivo/genética , Proteína Rica em Cisteína 61 , Resistencia a Medicamentos Antineoplásicos/genética , Receptor alfa de Estrogênio/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Tamoxifeno/farmacologia , Fatores de Transcrição , Proteínas de Sinalização YAPRESUMO
The occupant's posture can be changeable to an inadvertent or unintentional out-of-seat position (OOSP) depend on their convenience. Understanding for OOSP has been demanded, but it is not sufficient; especially when AEB is activated. The aim of the current study was to characterize the motion responses of an occupant in various OOSPs when AEB is activated and to identify if there were any additional risks of injury or discomfort to the occupant. The normal seat position (NSP) and three OOSPs were defined to compare the difference of human responses, and six healthy males were participated. Particularly, the maximum rotation angles of the neck in OOSP2 and OOSP3 differed significantly around 1.3 ± 0.3 and 1.4 ± 0.2 times higher respectively than from in the NSP (p < 0.05). Occupants assuming OOSP3 exhibited motion characteristics were not restrained effectively and characterized a hovering and falling upper body and a slipping pelvis. This study has identified, for the first time, a potential risk of injury or discomfort when AEB is activated while an occupant is in an OOSP. This study may serve as fundamental data for the development of safety system that can improve restraint and counteract any deterioration in occupant safety.