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BACKGROUND: Acute lung injury (ALI) is a devastating condition caused by sepsis, pneumonia, trauma, and more recently, COVID-19. SH003, an herbal formula consisted of Astragalus membranaceus, Angelica gigas and Trichosanthes kirilowii, is known for its effects on cancer and immunoregulation. HYPOTHESIS/PURPOSE: Previous studies show SH003 exerts a promising anti-inflammatory effect. This study investigates the effect of modified SH003 on ALI using in silico, in vivo, and in vitro models. STUDY DESIGN AND METHODS: We performed in silico-based analysis of SH003 on ALI-related pathways. C57BL/6 mice were intraperitoneally subjected to lipopolysaccharide (LPS) to induce septic ALI, followed by oral administration of SH003 for 2 weeks. Dexamethasone was used as the positive control. Human peripheral blood-derived polymorphonuclear neutrophils (PMN) were used to investigate the effect and mechanisms of SH003 on neutrophil extracellular trap (NET) formation. RESULTS: Network pharmacology analysis suggested SH003 regulates lung inflammation by modulating NET formation. SH003 significantly reduced mortality in sepsis in vivo by inhibiting local and systemic inflammation, likely via nuclear factor kappa B and mitogen-activated protein kinase pathways-mediated inflammasome suppression. SH003 also decreased NET-related markers in lung tissues and inhibited LPS- and phorbol myristate acetate-induced NET formation in PMN. Cytometry time-of-flight analysis confirmed regulation of NETosis-related pathways by SH003. CONCLUSION: SH003 effectively inhibits excessive immune responses in the lung by suppressing inflammasome activation and NET formation. These findings suggest SH003 as a potential therapeutic agent for septic ALI.
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Background and Objectives: Obstructive sleep apnea (OSA) is common in cardiovascular disease (CVD), although positive airway pressure (PAP) treatment has not been demonstrated to improve the cardiovascular outcome. The objective of this study is to investigate the impact of adherence to PAP therapy on cardiopulmonary exercise testing (CPET) performance in patients with concomitant OSA and CVD. Materials and Methods: This preliminary study involved symptomatic OSA patients requiring PAP treatment who had CVD. All subjects underwent polysomnography, echocardiography, and CPET at baseline. After 6 to 12 months of PAP treatment, CPET performance was re-assessed. The changes in CPET parameters before and after PAP treatment were compared between patients who were adherent to PAP and patients who were not adherent to PAP. Results: A total of 16 OSA patients with an apnea-hypopnea index of 32.0 ± 23.4 were enrolled. Patients were classified into the adherent (n = 9) and non-adherent (n = 7) groups with regard to PAP adherence. After 6 to 12 months of PAP treatment, the PAP-adherent group showed a greater increase in peak VO2 than the PAP-non-adherent group, but the difference between the two groups was not significant (p = 0.581). The decrease in ventilatory equivalent for the carbon dioxide slope (VE/VCO2) was significantly greater in the PAP-adherent group compared to the PAP-non-adherent group (p = 0.030). Conclusions: Adherence to PAP therapy for OSA is associated with an improvement in the VE/VCO2 slope, as an index of the ventilatory response to exercise, in patients with CVD. Screening for sleep apnea in CVD patients may be warranted, and strategies to optimize adherence to PAP in these patients are beneficial. Further evidence is needed to elucidate whether CPET could be routinely used to monitor treatment responses of OSA to PAP therapy in patients with CVD.
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Aptidão Cardiorrespiratória , Doenças Cardiovasculares , Teste de Esforço , Polissonografia , Apneia Obstrutiva do Sono , Humanos , Apneia Obstrutiva do Sono/terapia , Apneia Obstrutiva do Sono/fisiopatologia , Apneia Obstrutiva do Sono/complicações , Masculino , Feminino , Pessoa de Meia-Idade , Doenças Cardiovasculares/fisiopatologia , Doenças Cardiovasculares/complicações , Teste de Esforço/métodos , Aptidão Cardiorrespiratória/fisiologia , Polissonografia/métodos , Pressão Positiva Contínua nas Vias Aéreas/métodos , Idoso , Adulto , Cooperação do Paciente/estatística & dados numéricosRESUMO
BACKGROUND & OBJECTIVE: Aortic dissection (AD) is a serious condition requiring rapid and accurate diagnosis. In this study, we aimed to improve the diagnostic accuracy of AD by presenting a novel method for aortic segmentation in computed tomography images that uses a combination of a transformer and a UNet cascade network with a Zoom-Out and Zoom-In scheme (ZOZI-seg). METHODS: The proposed method segments each compartment of the aorta, comprising the true lumen (TL), false lumen (FL), and thrombosis (TH) using a cascade strategy that captures both the global context (anatomical structure) and the local detail texture based on the dynamic patch size with ZOZI schemes. The ZOZI-seg model has a two-stage architecture using both a "3D transformer for panoptic context-awareness" and a "3D UNet for localized texture refinement." The unique ZOZI strategies for patching were demonstrated in an ablation study. The performance of our proposed ZOZI-seg model was tested using a dataset from Asan Medical Center and compared with those of existing models such as nnUNet and nnFormer. RESULTS: In terms of segmentation accuracy, our method yielded better results, with Dice similarity coefficients (DSCs) of 0.917, 0.882, and 0.630 for TL, FL, and TH, respectively. Furthermore, we indirectly compared our model with those in previous studies using an external dataset to evaluate its robustness and generalizability. CONCLUSIONS: This approach may help in the diagnosis and treatment of AD in different clinical situations and provide a strong basis for further research and clinical applications.
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Dissecção Aórtica , Tomografia Computadorizada por Raios X , Humanos , Dissecção Aórtica/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , AlgoritmosRESUMO
Purpose: This study aimed to investigate which indirect parameters on preoperative MRI were the principal predictors of subscapularis tendon tears (STTs) requiring surgical repair. Materials and Methods: Preoperative MRI scans of 86 patients were retrospectively reviewed for visual assessment of the STT, pathology of the long head of the biceps tendon (LHBT), posterior decentering (PD) of the humeral head, humeral rotation, fatty degeneration, and subscapularis muscle atrophy. To evaluate atrophy, visual grading using the anatomical line connecting the coracoid tip to the glenoid base, designated as the base-to-tip line (BTL), and thickness measurements were performed in the en-face view. Results: Arthroscopically, 31 patients (36%) exhibited Lafosse type III or IV STT and underwent surgical repair. LHBT pathology (p = 0.002), PD of the humeral head (p = 0.012), fatty degeneration (p < 0.001), and BTL grade (p = 0.003) significantly correlated with STT. In the multivariate analysis, PD of the humeral head (p = 0.011, odds ratio [OR] = 5.14) and fatty degeneration (p = 0.046, OR = 2.81) were independent predictors of STT. Conclusion: PD of the humeral head and fatty degeneration of the subscapularis can help to diagnose clinically significant STT. Interpretation of these findings may contribute to the planning of an optimal surgical strategy.
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The azygos venous system is a crucial conduit of the posterior thorax and potentially vital collateral pathway. However, it is often overlooked clinically and radiologically. This pictorial essay reviews the normal azygos venous anatomy and CT findings of congenital variations and structural changes associated with acquired pathologies.
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Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide, and despite advances in treatment, survival rates are still low; therefore, the development of novel drugs is imperative. Acetylcorynoline (ACN) is derived from Corydalis ambigua Cham. et Schltdl tubers. The effect of ACN on colon cancer is still unknown. Therefore, we investigated its potential effects. Our data showed that ACN inhibited cell viability and proliferation. Moreover, ACN induced apoptosis and cell cycle arrest by inhibiting cell growth. In the present study, we hypothesized that ACN regulates c-Myc through CNOT2 or MID1IP1. ACN reduced the protein expression of oncogenic genes, decreased c-Myc half-life, and rapidly inhibited the serum stimulation response. Moreover, knockdown of CNOT2 and MID1IP1 with ACN increased apoptosis and further reduced the expression of oncogenes. In addition, ACN exhibited a synergistic effect with low-dose 5-fluorouracil (5-FU) and doxorubicin (Dox). Collectively, our data demonstrate that ACN inhibited c-Myc expression through CNOT2 and MID1IP1, and induced apoptosis. These findings indicate the potential of ACN as a therapeutic agent against colon cancer.
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Neoplasias do Colo , Transdução de Sinais , Humanos , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Proto-Oncogênicas c-myc/metabolismo , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/metabolismo , Pontos de Checagem do Ciclo Celular , Apoptose , Fluoruracila/farmacologia , Mitose , Proliferação de Células , Linhagem Celular Tumoral , Proteínas Repressoras/genéticaRESUMO
RNA-binding motif protein 10 (RBM10) is a frequently mutated tumor suppressor in lung adenocarcinoma (LUAD). Yet, it remains unknown whether cancer-derived mutant RBM10 compromises its tumor suppression function and, if so, the molecular insight of the underlying mechanisms. Here, we show that wild-type RBM10 suppresses lung cancer cell growth and proliferation by inactivating c-Myc that is essential for cancer cell survival. RBM10 directly binds to c-Myc and promotes c-Myc's ubiquitin-dependent degradation, while RBM10 knockdown leads to the induction of c-Myc level and activity. This negative action on c-Myc is further boosted by ribosomal proteins (RPs) uL18 (RPL5) and uL5 (RPL11) via their direct binding to RBM10. Cancer-derived mutant RBM10-I316F fails to bind to uL18 and uL5 and to inactivate c-Myc, thus incapable of suppressing tumorigenesis. Our findings uncover RBM10 as a pivotal c-Myc repressor by cooperating with uL18 and uL5 in lung cancer cells, as its failure to do so upon mutation favors tumorigenesis.
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Neoplasias Pulmonares , Proteínas Proto-Oncogênicas c-myc , Proteínas de Ligação a RNA , Proteínas Ribossômicas , Humanos , Carcinogênese , Proliferação de Células/genética , Transformação Celular Neoplásica , Neoplasias Pulmonares/genética , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Proto-Oncogênicas c-myc/metabolismo , Proteínas Ribossômicas/genética , Proteínas Ribossômicas/metabolismo , Motivos de Ligação ao RNA , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismoRESUMO
Type 2 diabetes (T2D) is a serious health issue with increasing incidences worldwide. However, current medications have limitations due to side effects such as decreased appetite, stomach pain, diarrhea, and extreme tiredness. Here, we report the effect of fermented ice plant (FMC) in the T2M mouse model of db/db mice. FMC showed a greater inhibition of lipid accumulation compared to unfermented ice plant extract. Two-week oral administration with FMC inhibited body weight gain, lowered fasting blood glucose, and improved glucose tolerance. Serum parameters related to T2D including insulin, glycosylated hemoglobin, adiponectin, and cholesterols were improved as well. Histological analysis confirmed the protective effect of FMC on pancreas and liver destruction. FMC treatment significantly increased the expression and phosphorylation of IRS-1, PI3K, and AKT. Additionally, AMP-activated protein kinase phosphorylation and nuclear factor erythroid 2-related factor 2 were also increased in the liver tissues of db/db mice treated with FMC. Overall, our results indicate the anti-diabetic effect of FMC; therefore, we suggest that FMC may be useful as a therapeutic agent for T2D.
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In this study, we investigated the potential anticancer effects of Viscum album, a parasitic plant that grows on Malus domestica (VaM) on breast cancer cells, and explored the underlying mechanisms. VaM significantly inhibited cell viability and proliferation and induced apoptosis in a dose-dependent manner. VaM also regulated cell cycle progression and effectively inhibited activation of the STAT3 signaling pathway through SHP-1. Combining VaM with low-dose doxorubicin produced a synergistic effect, highlighting its potential as a promising therapeutic. In vivo, VaM administration inhibited tumor growth and modulated key molecular markers associated with breast cancer progression. Overall, our findings provide strong evidence for the therapeutic potential of VaM in breast cancer treatment and support further studies exploring clinical applications.
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Neoplasias da Mama , Viscum album , Humanos , Feminino , Viscum album/metabolismo , Neoplasias da Mama/metabolismo , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Apoptose , Transdução de Sinais , Proliferação de Células , Linhagem Celular Tumoral , Fator de Transcrição STAT3/metabolismoRESUMO
Pancreatic cancer(PC) is less common than other cancers; however, it has a poor prognosis. Therefore, studying novel target signaling and anticancer agents is necessary. Momordicae Semen (MS), the seed of Momordica sochinensis Spreng, mainly found in South-East Asia, including China and Bangladesh, is used to treat various diseases because of its anticancer, antioxidant, anti-inflammatory, and antibacterial properties. However, the effect of the MS extract on pancreatic cancer cells remains unknown. In this study investigated whether the MS extract exerted an anti-cancer effect by regulating c-Myc through CNOT2. Cytotoxicity and proliferation were investigated using MTT and colony formation assays. The levels of apoptotic, oncogenic, and migration-associated factors were confirmed using immunoblotting and immunofluorescence. Wound closure was analyzed using a wound healing assay. The chemical composition of the MS methanol extracts was analyzed using liquid chromatography-mass spectrometry. We confirmed that the MS extract regulated apoptotic factors and attenuated the stability of c-Myc and its sensitivity to fetal bovine serum. Furthermore, the MS extract increased apoptosis by regulating c-Myc and CNOT2 expression and enhanced the sensitivity of 5-FU in pancreatic cancer. This study showed that the MS extract is a promising new drug for PC.
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Antineoplásicos , Neoplasias Pancreáticas , Humanos , Linhagem Celular Tumoral , Sementes , Apoptose , Antineoplásicos/farmacologia , Neoplasias Pancreáticas/tratamento farmacológico , Extratos Vegetais/química , Proliferação de Células , Proteínas Repressoras/farmacologia , Neoplasias PancreáticasRESUMO
BACKGROUND: HFA-PEFF and cardiopulmonary exercise testing (CPET) are comprehensive diagnostic tools for heart failure with preserved ejection fraction (HFpEF). We aimed to investigate the incremental prognostic value of CPET for the HFA-PEFF score among patients with unexplained dyspnea with preserved ejection fraction (EF). METHODS: Consecutive patients with dyspnea and preserved EF (n = 292) were enrolled between August 2019 and July 2021. All patients underwent CPET and comprehensive echocardiography, including two-dimensional speckle tracking echocardiography in the left ventricle, left atrium and right ventricle. The primary outcome was defined as a composite cardiovascular event including cardiovascular-related mortality, acute recurrent heart failure hospitalization, urgent repeat revascularization/myocardial infarction or any hospitalization due to cardiovascular events. RESULTS: The mean age was 58 ± 14.5 years, and 166 (56.8%) participants were male. The study population was divided into three groups based on the HFA-PEFF score: < 2 (n = 81), 2-4 (n = 159), and ≥ 5 (n = 52). HFA-PEFF score ≥ 5, VE/VCO2 slope, peak systolic strain rate of the left atrium and resting diastolic blood pressure were independently associated with composite cardiovascular events. Furthermore, the addition of VE/VCO2 and HFA-PEFF to the base model showed incremental prognostic value for predicting composite cardiovascular events (C-statistic 0.898; integrated discrimination improvement 0.129, p = 0.032; net reclassification improvement 1.043, p ≤ 0.001). CONCLUSIONS: CPET could be exploited for the HFA-PEFF approach in terms of incremental prognostic value and diagnosis among patients with unexplained dyspnea with preserved EF.
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Insuficiência Cardíaca , Função Ventricular Esquerda , Humanos , Masculino , Adulto , Pessoa de Meia-Idade , Idoso , Feminino , Volume Sistólico/fisiologia , Insuficiência Cardíaca/diagnóstico , Prognóstico , Teste de Esforço/métodos , Dispneia/diagnóstico por imagem , Dispneia/complicaçõesRESUMO
We hypothesized that Euonymus sachalinensis (ES) induces apoptosis by inhibiting the expression of c-Myc in colon cancer cells, and this study proved that the methanol extract of ES has anticancer effects in colon cancer cells. ES belongs to the Celastraceae family and is well known for its medicinal properties. Extracts of species belonging to this family have been used to treat diverse diseases, including rheumatoid arthritis, chronic nephritis, allergic conjunctivitis, rhinitis, and asthma. However, ES has been targeted because there are currently few studies on the efficacy of ES for various diseases, including cancer. ES lowers cell viability in colon cancer cells and reduces the expression of c-Myc protein. We confirm that the protein level of apoptotic factors such as PARP and Caspase 3 decrease when ES is treated with Western blot, and confirm that DNA fragments occur through TUNEL assay. In addition, it is confirmed that the protein level of oncogenes CNOT2 and MID1IP1 decrease when ES is treated. We have also found that ES enhances the chemo-sensitivity of 5-FU in 5-FU-resistant cells. Therefore, we confirm that ES has anticancer effects by inducing apoptotic cell death and regulating the oncogenes CNOT2 and MID1IP1, suggesting its potential for use in the treatment of colon cancer.
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Neoplasias do Colo , Euonymus , Humanos , Neoplasias do Colo/metabolismo , Apoptose , Linhagem Celular Tumoral , Fluoruracila/farmacologia , Proliferação de Células , Proteínas RepressorasRESUMO
Inflammation causes a protective immune response, which can be observed by examining the inflammatory responses of macrophages. Macrophages release various immunostimulatory factors when destroying external pathogens. We induced lipopolysaccharides (LPS) in RAW 264.7 cells, a macrophage cell line, to determine whether Helixor-M can cause immuno-suppression. Helixor-M is known to have anticancer and immune effects. However, an indicator that regulates immunity has not been clearly confirmed. To this end, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was conducted to confirm Helixor-M was not cytotoxic. Western blotting and real-time polymerase chain reaction (RT-PCR) confirmed the anti-inflammatory effects. Additionally, immunofluorescence assay confirmed the translocation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) p65, a representative inflammatory pathway. Helixor-M was found to be non-cytotoxic, induce the NF-κB pathway, and reduce the levels of pro-inflammatory cytokine and mitogen-activated protein kinase (MAPK). We found Helixor-M affected the PI3K/AKT/JNK pathway. Therefore, we confirmed Helixor-M acts as an anti-inflammatory agent through NF-κB, TLR4 and PI3K inhibition and that it could be an effective immunosuppressive drug.
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Coiled-coil domain containing 3 (CCDC3) was previously shown to regulate liver lipid metabolism as a secretory protein. Here, we report an unexpected intracellular role of CCDC3 as a tumor suppressor in breast cancer (BrC). Bioinformatics datasets analysis showed that CCDC3 is under-expressed in BrCs, while its higher levels are correlated with higher overall survival and lower relapse of cancer patients, and CCDC3 is positively correlated with p53 and its target genes. Ectopic CCDC3 markedly suppressed proliferation, colony formation, and xenograft tumor growth by augmenting p53 activity in BrC cells. Depletion of endogenous CCDC3 by CRISPR-Cas9 increased proliferation and drug resistance of BrC cells by alleviating 5-Fluorouracil (5-FU)-induced p53 level and activity. Mechanistically, CCDC3 bound to the C-termini of p53 and MDM2, consequently stabilizing p53 in the nucleus and impairing MDM2 recruitment of p53 to the 26S proteosome without inhibiting p53 ubiquitination. p53 induced CCDC3 expression by binding to its promoter in BrC cells. Our results unveil a unique mechanism underlying CCDC3 activation of p53 in a positive feedback fashion to suppress BrC growth.
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Neoplasias da Mama , Proteína Supressora de Tumor p53 , Feminino , Humanos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Fígado/metabolismo , Recidiva Local de Neoplasia/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , Proteínas Proto-Oncogênicas c-mdm2/genética , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , UbiquitinaçãoRESUMO
Ophiopogonin D (OP-D), which is extracted from the root tuber of Ophiopogon japonicus, is well known for its anti-inflammatory, anti-oxidant, and anti-cancer effects. It is also therapeutic for various diseases such as diabetic myocardial injuries, obesity, atopic dermatitis, and osteoporosis. However, there are insufficient reports on the anti-cancer effects and molecular mechanisms of OP-D in colorectal cancer. Therefore, this study aimed to investigate the anti-cancer-modulating effect of OP-D on colorectal cancer. The study proved that OP-D (20-40 uM) has significant cell viability inhibition and anti-proliferative effects in Cell Counting Kit-8 (CCK-8) assay and colony formation assay. In addition, our immunofluorescence analysis data showed that OP-D (40 uM) inhibited the expression of Ki67, a cell proliferation marker, and confirmed that OP-D could induce nucleolar stress by depletion of IPO7 and XPO1. Furthermore, our western blot data showed that OP-D induced p53 expression via ribosomal protein (RP) L5 or L11 and inhibited c-Myc expression through CNOT2 in a dose-dependent manner. Additionally, OP-D regulated cyclin D1 and CDK4, which are well known as cell cycle regulatory proteins. OP-D consistently inhibited the phosphorylation of AKT expression in a dose-dependent manner. Furthermore, OP-D shortened c-Myc's half-life in a time-dependent manner. Furthermore, CNOT2 knockdown enhanced the inhibitory effect of OP-D on c-Myc in colon cancer cells. Besides that, we confirmed that OP-D has a combinational anti-cancer effect of 5-FU or doxorubicin to reduce cell viability and induce apoptosis through p53 and c-Myc regulation. Altogether, our results suggest that OP-D regulates colon cancer cell proliferation and induces apoptosis by inhibiting c-Myc expression via activation of p53 and CNOT2 regulation. The study demonstrated that OP-D may be a promising natural anti-cancer agent for the treatment of colorectal cancer.
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Colorectal cancer cell (CRC) is the fourth most common cancer in the world. There are several chemotherapy drugs available for its treatment, though they have side effects. Cycloastragenol (CY) is a compound from Astragalus membranaceus (Fisch.) Bge known to be effective in aging, anti-inflammatory, anticancer, and anti-heart failure treatments. Although many studies have demonstrated the functions of CY in cancer cells, no studies have shown the effects of p53 in colon cancer cells. In this study, we found that CY reduces the viability of colon cancer cells in p53 wild-type cells compared to p53 null cells and HT29. Furthermore, CY induces apoptosis by p53 activation in a dose- and time-dependent manner. And it was confirmed that it affects the L5 gene related to p53. Additionally, CY enhanced p53 expression compared to when either doxorubicin or 5-FU was used alone. Altogether, our findings suggest that CY induces apoptosis via p53 activation and inhibits the proliferation of colon cancer cells. In addition, apoptosis occurs in colon cancer cells due to other factors. Moreover, CY is expected to have a combined effect when used together with existing treatments for colon cancer in the future.
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Neoplasias do Colo , Proteína Supressora de Tumor p53 , Humanos , Apoptose , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/genética , Células HCT116 , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Antineoplásicos/farmacologiaRESUMO
Esophageal cancer (EC) is one of the most malignant types of cancer worldwide and has a high incidence and mortality rate in Asian countries. When it comes to treating EC, although primary methods such as chemotherapy and surgery exist, the prognosis remains poor. The purpose of this current research is to review the range of effects that natural products have on cancer by analyzing studies conducted on EC. Fifty-seven studies were categorized into four anti-cancer mechanisms, as well as clinical trials. The studies that were scrutinized in this research were all reported within five years. The majority of the substances reviewed induced apoptosis in EC, acting on a variety of mechanisms. Taken together, this study supports the fact that natural products have the potential to act as a candidate for treating EC.
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Produtos Biológicos , Neoplasias Esofágicas , Humanos , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Medicina Tradicional , Neoplasias Esofágicas/tratamento farmacológico , Descoberta de Drogas , IncidênciaRESUMO
Timosaponin A3 (TA3), extracted from the rhizome of Anemarrhenaasphodeloides Bunge, has been reported to affect various diseases, such as cancer, Alzheimer's disease, and allergies. However, the underlying molecular mechanisms and impacts are largely unknown. In the present study, we hypothesized that TA3 induces apoptosis through the inhibition of c-Myc expression via CNOT2 or MID1IP1 in HCT116. An MTT assay and colony formation assay were used to measure cell viability and proliferation. The protein expression of apoptotic markers and oncogenes was measured using immunoblotting and immunofluorescence assays. The interaction between MID1IP1 and c-Myc was confirmed by performing an immunoprecipitation assay. TA3 markedly inhibited colon cancer cell proliferation. Consistently, TA3 regulated the apoptotic proteins pro-PARP and caspase 3. TA3 inhibited the half-life of c-Myc and suppressed its expression in response to serum stimulation. In addition, TA3 enhanced the apoptotic effects of doxorubicin and 5-FU in colon cancer cells. Altogether, our results reveal a mechanism by which TA3 induces apoptosis through inhibiting c-Myc expression via CNOT2 or MID1IP1 in HCT116, which may help in the development of new therapies for colon cancer based on TA3 in the future.
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Neoplasias do Colo , Neoplasias Colorretais , Apoptose , Caspase 3/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias do Colo/patologia , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Fluoruracila/farmacologia , Fluoruracila/uso terapêutico , Células HCT116 , Humanos , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Proteínas Repressoras , Saponinas , EsteroidesRESUMO
There are limited data regarding the clinical impact of diabetes duration for patients with heavy calcified coronary lesions. We sought to determine the clinical impact of diabetes duration on clinical outcomes in patients with heavily calcified lesions who required rotational atherectomy during percutaneous coronary intervention (PCI). A total of 540 diabetic patients (583 lesions) were enrolled between January 2010 and October 2019. Patients were classified into three subgroups: patients with no diabetes mellitus (non-DM), shorter duration (S-DM), and longer duration (L-DM), of which duration was divided at 10 years. During 18 months of follow-up-duration, diabetes duration was significantly associated with the primary outcome. The incidence rate of target-vessel failure (TVF), the primary outcome, was significantly higher in the L-DM group compared with non-DM or S-DM. Among secondary outcomes, any repeat revascularization (RR) was frequently observed in the L-DM compared with other groups. In multivariate analysis, the risk of TVF and any RR was 1.9 times and 2.4 times higher in L-DM than in non-DM, respectively. This study firstly demonstrated that there is an association between a longer DM duration and poor clinical outcomes in patients with severe calcified CAD after PCI. More careful monitoring for recurrence is needed during follow-up in those patients.