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Psoriasis is a chronic, immune-mediated inflammatory skin disease with many complications and a poor prognosis that imposes a significant burden on individuals and society. Narrowband ultraviolet B (NB-UVB) represents a cost-effective non-drug therapeutic intervention for psoriasis. East Asian herbal medicine (EAHM) is currently being investigated for its potential as a safe and effective psoriasis treatment. Consequently, it has the potential to be employed as a combination therapy with NB-UVB. The objective was to ascertain the efficacy and safety of the EAHM with NB-UVB combination therapy and to identify important drugs for further research. In this study, randomized controlled trials (RCTs) were retrieved from ten databases in Korea, China, and Japan. All statistical analyses were conducted using R software version 4.3.0. The primary outcomes were the Psoriasis Area and Severity Index (PASI) and the incidence rate of adverse events (AEs), while the secondary outcomes were hematologic markers and the Dermatology Life Quality Index (DLQI), which reflect the immune-mediated inflammatory pathology of psoriasis. The analysis of 40 RCTs, including 3521 participants, demonstrated that EAHM with NB-UVB combination therapy exhibited a statistically significant superiority over NB-UVB monotherapy with respect to primary and secondary outcomes. The Bayesian network meta-analysis revealed that Investigator Presciption 3 and Ziyin Liangxue Decoction exhibited a consistent relative advantage with respect to each PASI-based efficacy metric. The network analysis estimated the potential influence ranking for all individual herbs according to PageRank centrality. The findings of this study suggest that EAHMs co-administered with NB-UVB may provide additional efficacy and safety-related benefits for patients with psoriasis. However, the quality of evidence is still low, and further high-quality trials are needed to reach more definitive conclusions.
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Medicina Tradicional de Asia Oriental , Psoriasis , Terapia Ultravioleta , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Administración Oral , Teorema de Bayes , Terapia Combinada , Medicamentos Herbarios Chinos/administración & dosificación , Medicamentos Herbarios Chinos/uso terapéutico , Medicina Tradicional de Asia Oriental/métodos , Metaanálisis en Red , Psoriasis/tratamiento farmacológico , Psoriasis/radioterapia , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del Tratamiento , Terapia Ultravioleta/métodos , Terapia Ultravioleta/efectos adversosRESUMEN
BACKGROUND/AIM: Hepatocellular carcinoma (HCC) is a main type of liver cancer with high metastatic potential, and its incidence is steadily increasing worldwide. However, the development of new drugs for the treatment of HCC is still insufficient. This study aimed to determine the anticancer effect of NSC-38270, a natural product, on HCC. MATERIALS AND METHODS: After treating HCC Huh7 cells with NSC-38270, cell growth, wound healing, migration, and invasion assays were conducted. We investigated the effects of NSC-38270 on Twist1, a crucial epithelial-mesenchymal transition (EMT)-related transcription factor. In addition, apoptosis, histone H2A.X activation, and cell morphology assays were performed in Huh7 and immortalized normal liver cells following treatment with NSC-38270. RESULTS: NSC-38270 reduced the migration and invasion ability of Huh7 cells, accompanied by a decrease in Twist1. Furthermore, NSC-38270 induced apoptosis in Huh7 cells, whereas apoptosis was not observed in immortalized normal liver cells (THLE-2 cells and Chang liver cells). CONCLUSION: NSC-38270 exhibited significant inhibitory effects on the migration and invasion of Huh7 cells by repressing Twist1. Importantly, it induced cancer cell-specific apoptotic effects. These findings suggest that NSC-38270 holds promising potential as a therapeutic candidate for cancer treatment.
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Apoptosis , Carcinoma Hepatocelular , Movimiento Celular , Neoplasias Hepáticas , Proteína 1 Relacionada con Twist , Humanos , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/metabolismo , Apoptosis/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Proteína 1 Relacionada con Twist/metabolismo , Proteína 1 Relacionada con Twist/genética , Línea Celular Tumoral , Invasividad Neoplásica , Proliferación Celular/efectos de los fármacos , Proteínas Nucleares/metabolismo , Proteínas Nucleares/genética , Transición Epitelial-Mesenquimal/efectos de los fármacosRESUMEN
Thermal ionization mass spectrometry is a powerful analytical technique that allows for precise determination of isotopic ratios. Analysis of low abundance samples, however, can be limited by the ionization efficiency. Following an investigation into a new type of metal-organic hybrid material, nanoporous ion emitters (nano-PIEs), devised to promote the emission of analyte ions and reduce traditional sample loading challenges, this work evaluates the impact that changing the metal in the material has on the ionization of uranium (U). Being derived from metal-organic frameworks (MOFs), nano-PIEs inherit the tunability of their parent MOFs. The MOF-74 series has been well studied for probing the impact various framework metals (i.e., Mg, Mn, Co, Ni, Cu, Zn, and Cd) have on material properties, and thus, a series of nano-PIEs with different metals were derived from this isoreticular MOF series. Trends in ionization efficiency were studied as a function of ionization potential, volatility, and work function of the framework metals to gain a better understanding of the mechanism of analyte ionization. This study finds a correlation between the analyte ionization efficiency and nano-PIE framework metal volatility that is attributed to its tunable thermal stability and degradation behavior.
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BACKGROUND: Rheumatoid arthritis is a chronic inflammatory autoimmune disease characterized by a wide range of clinical symptoms affecting various bodily functions, including skeletal, vascular, metabolic, and cognitive functions. This review aimed to evaluate the efficacy and safety of integrative medicine (East Asian herbal medicine combined with conventional medicine) used for the treatment of inflammatory pain in rheumatoid arthritis and to identify key candidate drugs based on the data. METHODS: A comprehensive literature search will be conducted in 4 core databases (PubMed, Excerpta Medica database, Cochrane Library, and Cumulative Index to Nursing & Allied Health Literature) 4 Korean databases (Oriental Medicine Advanced Searching Integrated System, Korean Studies Information Service System, Research Information Service System, and Korea Citation Index), 2 Chinese databases (Chinese National Knowledge Infrastructure Database and Wanfang data), and 1 Japanese database (Citation Information by National Institute of Informatics) for randomized controlled trials from December 13, 2022. Statistical analysis will be performed using R version 4.1.2 and R Studio program. The American College of Rheumatology 20/50/70 score and rate of adverse events will be the primary outcomes. All outcomes will be analyzed using a random-effects model to produce more statistically conservative results. Sensitivity, meta-regression, and subgroup analyses will be used to identify the sources of any heterogeneity in the study. The revised tool for assessing the risk of bias in randomized trials, version 2.0, will be used to evaluate methodological quality. The overall quality of evidence will be assessed according to the Grading of Recommendations Assessment, Development, and Evaluation Pro Framework. ETHICS AND DISSEMINATION: There are no ethical issues, as no primary data will be collected directly from the participants. The results of this review will be reported in a peer-reviewed scientific journal. TRIAL REGISTRATION: PROSPERO registration number: CRD42023412385.
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Artritis Reumatoide , Medicamentos Herbarios Chinos , Medicina Integrativa , Medicina Tradicional de Asia Oriental , Humanos , Artritis Reumatoide/complicaciones , Artritis Reumatoide/tratamiento farmacológico , Medicamentos Herbarios Chinos/uso terapéutico , Medicina Tradicional de Asia Oriental/métodos , Metaanálisis como Asunto , Dolor/tratamiento farmacológico , Extractos Vegetales , Proyectos de Investigación , Revisiones Sistemáticas como Asunto , Resultado del TratamientoRESUMEN
Cascade hydroxyl radical generating hydrogel reactor structures including a chemotherapeutic agent are invented for multiple treatment of breast cancer. Glucose oxidase (GOx) and cupric sulfate (Cu) are introduced for transforming accumulated glucose (in cancer cells) to hydroxyl radicals for starvation/chemodynamic therapy. Cu may also suppress cancer cell growth via cuproptosis-mediated cell death. Berberine hydrochloride (BER) is engaged as a chemotherapeutic agent in the hydrogel reactor for combining with starvation/chemodynamic/cuproptosis therapeutic modalities. Moreover, Cu is participated as a gel crosslinker by coordinating with catechol groups in hyaluronic acid-dopamine (HD) polymer. Controlling viscoelasticity of hydrogel reactor can extend the retention time following local injection and provide sustained drug release patterns. Low biodegradation rate of designed HD/BER/GOx/Cu hydrogel can reduce dosing frequency in local cancer therapy and avoid invasiveness-related inconveniences. Especially, it is anticipated that HD/BER/GOx/Cu hydrogel system can be applied for reducing size of breast cancer prior to surgery as well as tumor growth suppression in clinical application.
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Apoptosis , Neoplasias de la Mama , Neoplasias , Femenino , Humanos , Neoplasias de la Mama/tratamiento farmacológico , Catálisis , Línea Celular Tumoral , Glucosa Oxidasa/metabolismo , Hidrogeles , Peróxido de Hidrógeno/química , Radical Hidroxilo/química , Neoplasias/terapia , CobreRESUMEN
Parkinson's disease (PD) is one of the most common neurodegenerative diseases caused by the loss of dopaminergic neurons in the substantia nigra pars compacta. Although the etiology of PD is still unclear, the death of dopaminergic neurons during PD progression was revealed to be associated with abnormal aggregation of α-synuclein, elevation of oxidative stress, dysfunction of mitochondrial functions, and increased neuroinflammation. In this study, the effects of Licochalcone D (LCD) on MG132-induced neurotoxicity in primitive neural stem cells (pNSCs) derived from reprogrammed iPSCs were investigated. A cell viability assay showed that LCD had anti-apoptotic properties in MG132-induced oxidative-stressed pNSCs. It was confirmed that apoptosis was reduced in pNSCs treated with LCD through 7-AAD/Annexin â ¤ staining and cleaved caspase3. These effects of LCD were mediated through an interaction with JunD and through the EGFR/AKT and JNK signaling pathways. These findings suggest that LCD could be a potential antioxidant reagent for preventing disease-related pathological phenotypes of PD.
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The level of collagen production critically determines skin wound contraction. If an intelligent skin drug delivery technology that enables collagen production in a specific wound skin area is developed, a breakthrough in wound healing treatment would be expected. However, such an intelligent drug delivery technology has not yet been developed as much as in the field of anticancer therapy. In this study, we propose a smart drug delivery system using polymeric nanovehicles (PNVs), in which the periphery is conjugated with a fibroblast-targeting collagen-derived peptide, KTTKS (Lys-Thr-Thr-Lys-Ser). We showed that surface engineering of PNVs with simultaneous PEGylation and peptide patching improved the dispersibility of PNVs, while promoting selective cellular uptake to fibroblasts via PAR-2 receptor-mediated endocytosis. In vitro collagen production and in vivo wound healing assays revealed that curcumin-loaded fibroblast-targeting PNVs significantly enhanced collagen production and wound healing activities, thus promising effective skin tissue regeneration.
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Receptor PAR-2 , Cicatrización de Heridas , Piel , Colágeno/farmacología , Fibroblastos , EndocitosisRESUMEN
Colorectal cancer (CRC) is a very common and deadly cancer worldwide, and oxaliplatin is used as first-line chemotherapy. However, resistance usually develops, limiting treatment. Echinatin (Ech) is the main component of licorice and exhibits various therapeutic effects on inflammation-mediated diseases and cancer, ischemia/reperfusion, and liver injuries. The present study elucidated the underlying molecular mechanism of Ech-induced apoptosis in both oxaliplatin-sensitive (HT116 and HT29) and -resistant (HCT116-OxR and HT29-OxR) CRC cells. To evaluate the antiproliferative activities of Ech, we performed MTT and soft agar assays. Ech reduced viability, colony size, and numbers of CRC cells. The underlying molecular mechanisms were explored by various flow cytometry analyses. Ech-induced annexin-V stained cells, reactive oxygen species (ROS) generation, cell cycle arrest, JNK/p38 MAPK activation, endoplasmic reticulum (ER) stress, mitochondrial membrane potential depolarization, and multi-caspase activity. In addition apoptosis-, cell cycle-, and ER stress-related protein levels were confirmed by western blotting. Moreover, we verified ROS-mediated cell death by treatment with inhibitors such as N-acetyl-L-cysteine, SP600125, and SB203580. Taken together, Ech exhibits anticancer activity in oxaliplatin-sensitive and -resistant CRCs by inducing ROS-mediated apoptosis through the JNK/p38 MAPK signaling pathway. This is the first study to show that Ech has the potential to treat drug-resistant CRC, providing new directions for therapeutic strategies targeting drug-resistant CRC.
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Neoplasias Colorrectales , Sistema de Señalización de MAP Quinasas , Humanos , Especies Reactivas de Oxígeno/metabolismo , Oxaliplatino/farmacología , Línea Celular Tumoral , Apoptosis , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/metabolismoRESUMEN
Recently, medium-sized earthquakes such as the Gyeongju 9.12 earthquake (September 12, 2016, ML = 5.8) and the Pohang earthquake (November 15, 2017, ML = 5.4) occurred in Korea, thereby increasing social concern about earthquakes. Because Korea is not located near the Circum-Pacific Belt, also referred to as the "Ring of Fire", people in Korea are not used to earthquake disasters. Coastal areas in Korea are lined with multiple mega-cities and major industrial facilities. Most of them constructed on landfill, they have a high threat level to the damage to populations and structures leading to complex disasters in the event of an earthquake. However, studies of seismic hazards in ports is incomplete compared with those of onshore sites. Improving the understanding of seismic hazards and characterizing them catching up with related research from various perspectives being actively conducted. In this study, the site-specific response characteristics of the Pohang International Container Terminal in Pohang Yeongil New Port were analyzed using the S-wave energy of 10 sets of ground motions recorded by seismic accelerometers operated by the Ministry of Oceans and Fisheries based on the horizontal-to-vertical spectral ratio (H/V ratio) method. As a result of analysis, the H/V ratio curves show that the peak frequency values for the target site averages 9 Hz, and the natural period values of the site were preliminarily predicted to average 0.11 s. In addition, site amplification characteristics are different based on the seismic wave calculation method. The result can be used as data for identifying ground dynamic characteristics and verifying the site amplification coefficients and design spectrum in the seismic design.
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Desastres , Terremotos , Humanos , Instalaciones de Eliminación de Residuos , Ciudades , AcelerometríaRESUMEN
Induced pluripotent stem cells (iPSCs) can be generated from somatic cells using Oct4, Sox2, Klf4, and c-Myc (OSKM). Small molecules can enhance reprogramming. Licochalcone D (LCD), a flavonoid compound present mainly in the roots of Glycyrrhiza inflata, acts on known signaling pathways involved in transcriptional activity and signal transduction, including the PGC1-α and MAPK families. In this study, we demonstrated that LCD improved reprogramming efficiency. LCD-treated iPSCs (LCD-iPSCs) expressed pluripotency-related genes Oct4, Sox2, Nanog, and Prdm14. Moreover, LCD-iPSCs differentiated into all three germ layers in vitro and formed chimeras. The mesenchymal-to-epithelial transition (MET) is critical for somatic cell reprogramming. We found that the expression levels of mesenchymal genes (Snail2 and Twist) decreased and those of epithelial genes (DSP, Cldn3, Crb3, and Ocln) dramatically increased in OR-MEF (OG2+/+/ROSA26+/+) cells treated with LCD for 3 days, indicating that MET effectively occurred in LCD-treated OR-MEF cells. Thus, LCD enhanced the generation of iPSCs from somatic cells by promoting MET at the early stages of reprogramming.
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Reprogramación Celular , Células Madre Pluripotentes Inducidas , Humanos , Diferenciación Celular/genética , Células Madre Pluripotentes Inducidas/metabolismo , AceleraciónRESUMEN
Objective: Identifying the risks of completed suicide in suicide survivors is essential for policies supporting family members of suicide victims. We aimed to determine the suicide risk of suicide survivors and identify the number of suicides per 100,000 population of suicide survivors, bereaved families of traffic accident victims, and bereaved families with non-suicide deaths. Methods: This was a nationwide population-based cohort study in South Korea. The data were taken from the Korean National Health Insurance and Korea National Statistical Office between January 2008 and December 2017. The relationship between the decedent and the bereaved family was identified using the family database of the National Health Insurance Data. Age and gender were randomly matched 1:1 among 133,386 suicide deaths and non-suicide deaths. A proportional hazard model regression analysis was conducted after confirming the cumulative hazard using Kaplan-Meier curves to obtain the hazard ratio (HR) of completed suicide in suicide survivors. Results: Using 423,331 bereaved families of suicide victims and 420,978 bereaved families of non-suicide deaths as the control group, HR of completed suicide in suicidal survivors was found to be 2.755 [95% confidence limit (CL): 2.550-2.977]. HR for wives committing suicide after husbands' suicide was 5.096 (95% CL: 3.982-6.522), which was the highest HR among all relationships with suicide decedents. The average duration from suicide death to suicide of family members was 25.4 months. Among suicide survivors, the number of suicides per 100,000 people was 586, thrice that of people in bereaved families of traffic accident victims and in bereaved families of non-suicide deaths. Conclusion: The risk of completed suicide was three times higher in suicide survivors than in bereaved families with non-suicide deaths, and it was highest in wives of suicide decedents. Thus, socio-environmental interventions for suicidal survivors must be expanded.
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Background: Migraine is a relatively common disease that has a significant effect on the daily activities of affected individuals. The purpose of this study was to explore the effects of herbal medicine (Jodeungsan, JDS) on migraine. Methods: Sixty-four patients with migraine were recruited and randomized to either the JDS or placebo group at a 1:1 ratio. The subjects received JDS or placebo daily for four weeks. The primary outcome was a change in the number of headache attack days (HADs), and the secondary outcome measures were the headache impact test (HIT), migraine-specific quality of life (MSQoL), the deficiency and excess pattern identification questionnaire (DEPIQ), the cold and heat pattern identification questionnaire (CHPIQ), and the blood stasis pattern questionnaire (BSPQ). Results: In all, 61 of the 64 patients took the investigational drugs for four weeks. The number of HADs did not significantly differ between the JDS and placebo groups at the end of the study. However, the HIT and MSQoL results showed significant improvement over the baseline in both groups. Conclusion: JDS did not have a significant effect on chronic migraine. Larger studies are needed to confirm this result. Trial registration: Clinical Research Information Service (https://cris.nih.go.kr/): KCT0003121.
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Oxidative stress and chronic inflammation are closely linked to various diseases. However, previous studies have demonstrated that plant extracts could prevent and alleviate these adverse outcomes. Piper betle Linn. (Piper betle L.) is a cosmopolitan plant that belongs to the Piperaceae family, whose leaves are edible and possess several health benefits. This study sought to characterize the anti-inflammatory and antioxidant effects of a methanol extract of Piper betle L. leaves and stems (MPBLLS). MPBLLS was found to have a dose-dependent radical scavenging effect, as demonstrated by the 2,2-diphenyl-1-picrylhydrazyl assay. Additionally, MPBLLS inhibited the lipopolysaccharide (LPS)-stimulated production of nitric oxide and prostaglandin E2 by reducing the expression of inducible nitric oxide synthase and cyclooxygenase-2 in RAW 264.7 macrophages without affecting cell viability. Furthermore, our findings suggested that the inhibitory effects of MPBLLS on pro-inflammatory cytokines such as tumor necrosis factor-α, interleukin-1ß, and interleukin-6 were due to the inhibition of the nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways in LPS-treated RAW 264.7 macrophages. MPBLLS and hydroxychavicol, a major constituent of MPBLLS, suppressed LPS-induced translocation of NF-κB p65 from cytoplasm to nucleus. Interestingly, MPBLLS increased nuclear factor erythroid 2-related factor 2 (Nrf2) protein levels and transcription levels of Nrf2 target genes in a dose-dependent manner. Collectively, our findings suggest that MPBLLS could serve as a basis for the development of novel orally-administered therapies due to its inhibitory effects on oxidative and inflammatory stress. DATA AVAILABILITY: The data presented in this study are available on request from the corresponding author.
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FN-kappa B , Piper betle , Ratones , Animales , FN-kappa B/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , Antioxidantes/farmacología , Antioxidantes/metabolismo , Lipopolisacáridos/farmacología , Lipopolisacáridos/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Interleucina-1beta/metabolismo , Metanol/farmacología , Ciclooxigenasa 2/metabolismo , Óxido Nítrico/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Células RAW 264.7 , Interleucina-6/metabolismo , Antiinflamatorios/farmacología , Antiinflamatorios/metabolismo , Macrófagos , Extractos Vegetales/farmacología , Extractos Vegetales/metabolismo , Sistema de Señalización de MAP Quinasas , Citocinas/metabolismo , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Prostaglandinas/metabolismoRESUMEN
BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory disease that leads to a significant social burden. East Asian herbal medicine (EAHM) has long been used to treat RA. Therefore, a systematic study of how EAHM treatments can be developed into new drugs using specific materials is needed. METHODS: Eleven databases containing literature in English, Korean, Chinese, and Japanese were searched for randomized controlled trials comparing EAHM with conventional medicine (CM). A meta-analysis was performed on the variable data to assess their effects on inflammatory pain. Subsequently, we searched for core materials and combinations of core material-based data mining methods. RESULTS: A total of 186 trials involving 19,716 patients with RA met the inclusion criteria. According to the meta-analysis, EAHM had a significantly superior effect on continuous pain intensity, tender joint count, and response rate. Patients treated with EAHM had a significantly reduced incidence of adverse events compared with those treated with CM. Based on additional analysis of the EAHM formula data included in this meta-analysis, 21 core materials and five core herbal combinations were identified. CONCLUSION: EAHM remedies for RA have the adequate potential for use as candidate materials for treating inflammatory pain in RA. The candidate core herbs evaluated in this study act on multiple pathways and are expected to provide pain relief, sustained inflammation suppression, immune regulation, and prevention of joint destruction. It seems worthwhile to conduct follow-up research on drug development using the core materials derived from this review.
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Artritis Reumatoide , Medicamentos Herbarios Chinos , Humanos , Medicina de Hierbas , Medicamentos Herbarios Chinos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Medicina Tradicional China/métodos , Dolor/tratamiento farmacológico , Minería de DatosRESUMEN
BACKGROUND: Isolinderalactone (ILL), a sesquiterpene lactone compound, can be extracted from the root of Lindera aggregate. Physiological activities of ILL, including anti-inflammatory and anti-proliferative effects, have been investigated in multiple diseases. Nevertheless, little is known regarding its anti-cancer activities and the mechanism of action of ILL in targeting human CRC cells. PURPOSE: To determine ILL-mediated anti-proliferative effects on oxaliplatin (Ox)-sensitive and resistant colorectal cancer (CRC) cells and underlying mechanisms involved in its effects focusing on signal transduction. METHODS: Inhibitory effect of ILL on CRC cells was evaluated by analyzing mitochondrial membrane potential (MMP) dysfunction and multi-caspase activity. Apoptosis-regulating proteins and JNK/p38 signaling molecules were monitored by Western blotting. ROS-dependent physiological modifications by ILL were confirmed by pretreatment with N-acetylcysteine (NAC). Moreover, the involvement of JNK/p38 signaling in ROS-mediated apoptosis was verified by treatment with SP600125 (JNK inhibitor) and SB203580 (p38 inhibitor). RESULTS: ILL decreased cell viability and colony formation in both CRC Ox-sensitive (HCT116 and HT29) and Ox-resistant (OxR) (HCT116-OxR and HT29-OxR) cells. ILL induced G2/M phase cell cycle arrest, ROS generation, phosphorylated (p)JNK/p38 MAPK activation, mitochondrial membrane potential (MMP) depolarization, and multi-caspase activation, which eventually triggered apoptotic cell death of CRC cells. In addition, combined treatment with ILL and SP600125, SB203580, or pan-caspase inhibitor (Z-VAD-FMK) prevented decreases in cell viability seen after treatment with ILL alone. Pretreatment with NAC attenuated ILL-mediated apoptosis, ROS production, and p-JNK/p38 expression. CONCLUSION: Taken together, our results suggest that ILL can exert its anticancer effect in CRC Ox-sensitive and OxR cells by inducing ROS-mediated apoptosis through JNK/p38 MAPK signaling pathways. This is the first study demonstrating that ILL has a potential to improve drug efficacy against resistance mechanisms, providing a new insight into therapeutic strategies targeting drug-resistant CRC.
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Neoplasias Colorrectales , Sesquiterpenos , Apoptosis , Caspasas , Línea Celular Tumoral , Humanos , Proteínas Quinasas JNK Activadas por Mitógenos , Sistema de Señalización de MAP Quinasas , Oxaliplatino , Especies Reactivas de Oxígeno , Transducción de Señal , Proteínas Quinasas p38 Activadas por MitógenosRESUMEN
Deoxypodophyllotoxin (DPT), a naturally occurring flavonolignan, possesses several pharmacological properties, including anticancer property. However, the mechanisms underlying DPT mode of action in oral squamous cell carcinoma (OSCC) remain unknown. This study aimed to investigate the anticancer effects of DPT on OSCC and the underlying mechanisms. Results of the MTT assay revealed that DPT significantly reduced the cell viability in a time- and dose-dependent manner. Flow cytometry analysis revealed that DPT induces apoptosis in OSCC cells in a dose-dependent manner. Moreover, DPT enhanced the production of mitochondrial reactive oxygen species (ROS) in OSCC cells. Mechanistically, DPT induced apoptosis in OSCC cells by suppressing the PI3K/AKT signaling pathway while activating the p38 MAPK signaling to regulate the expression of apoptotic proteins. Treatment with SC79, an AKT activator, reversed the effects of DPT on AKT signaling in OSCC cells. Taken together, these results provide the basis for the use of DPT in combination with conventional chemotherapy for the treatment of oral cancer.
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Carcinoma de Células Escamosas , Flavonolignanos , Neoplasias de Cabeza y Cuello , Neoplasias de la Boca , Apoptosis , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , Línea Celular Tumoral , Proliferación Celular , Medicamentos Herbarios Chinos , Flavonolignanos/farmacología , Flavonolignanos/uso terapéutico , Humanos , Neoplasias de la Boca/tratamiento farmacológico , Neoplasias de la Boca/patología , Fosfatidilinositol 3-Quinasas/metabolismo , Podofilotoxina/análogos & derivados , Proteínas Proto-Oncogénicas c-akt/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Carcinoma de Células Escamosas de Cabeza y Cuello , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
Tannic acid (TA) not only prevents drug carriers from sticking to the glycocalyx layer of vascular endothelial cells but also has anti-cancer properties, thereby improving drug delivery efficiency in cancer treatment. This study proposes a TANNylated nanovesicle-based cancer treatment approach by utilizing the aforementioned advantages of TA. We fabricated cancer cell-targeting BC71 peptide-conjugated TANNylated nanovesicles (TANVBC71) by covalently bonding the TA derivative and BC71 (cyclo[ßA-kRK(3-maleimidopropionyl)-D-(D-2-naphthyl)]) with thiol-modified phospholipids through the thiol-maleimide reaction. We demonstrated that TANVBC71 was absorbed faster in high amounts by cancer cells than nanovesicles owing to its high affinity for the epidermal growth factor receptor and extracellular matrix components that are driven by van der Waals attraction as well as hydrogen bonding and hydrophobic interactions in a complex manner. These complex attractions of TANVBC71 for cancer cells led to the effective induction of cancer cell apoptosis. The findings obtained in this study highlight that the TANVBC71 system has the potential for intelligent high-efficacy cancer cell drug delivery.
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Células Endoteliales , Polifenoles , Apoptosis , Portadores de Fármacos/química , Polifenoles/farmacología , Compuestos de SulfhidriloRESUMEN
Licochalcone H (LCH) is a phenolic compound synthetically derived from licochalcone C (LCC) that exerts anticancer activity. In this study, we investigated the anticancer activity of LCH in human skin cancer A375 and A431 cells. The 3-(4,5-dimethylthiazol- 2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) cell viability assay was used to evaluate the antiproliferative activity of LCH. Cell cycle distribution and the induction of apoptosis were analyzed by flow cytometry. Western blotting assays were performed to detect the levels of proteins involved in cell cycle progression, apoptosis, and the JAK2/STAT3 signaling pathway. LCH inhibited the growth of cells in dose- and time-dependent manners. The annexin V/propidium iodide double staining assay revealed that LCH induced apoptosis, and the LCH-induced apoptosis was accompanied by cell cycle arrest in the G1 phase. Western blot analysis showed that the phosphorylation of JAK2 and STAT3 was decreased by treatment with LCH. The inhibition of the JAK2/STAT3 signaling pathway by pharmacological inhibitors against JAK2/STAT3 (cryptotanshinone (CTS) and S3I-201) simulated the antiproliferative effect of LCH suggesting that LCH induced apoptosis by modulating JAK2/STAT3 signaling.