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1.
Artículo en Inglés | MEDLINE | ID: mdl-39015948

RESUMEN

BACKGROUND: Despite extensive research on muscle loss in people living with HIV (PLWH), the prevalence and contributing factors specifically among middle-aged men remain unclear. This study aimed to determine the prevalence of low muscle mass within this demographic and to identify associated factors. METHODS: A total of 378 men living with HIV were enrolled in the study. They were classified into low muscle mass group if they displayed a skeletal muscle index (SMI) <7.00 kg/m2 or fell within the lowest quintile of SMI based on the criteria established by the Asian Working Group for Sarcopenia 2019. RESULTS: Out of the 378 men living with HIV enrolled, 351 had normal muscle mass, while 27 (7.1%) had low muscle mass. Antiretroviral drugs Zidovudine (AZT) (OR = 0.246, P = 0.022) and higher serum albumin levels (OR = 0.899, P = 0.026) were found to be protective factors against low muscle mass according to quintile grouping. Strong positive associations between SMI and body mass index (BMI), nutritional risk index (NRI), oedema index and fat-free mass index (FFMI) (R > 0.5, P < 0.001) were observed. In addition, both BMI (sensitivity = 0.741, specificity = 0.906) and NRI (sensitivity = 0.963, specificity = 0.601) had high sensitivity and specificity in diagnosing low muscle mass, with critical values of 19.85 and 114.177 for BMI and NRI, respectively. The oedema index was the most effective measure of body composition in detecting abnormal fluid retention with high sensitivity (92.6%) and moderate specificity (71.8%) in identifying individuals with low muscle mass. Notably, PLWH with low muscle mass participants had a significantly higher prevalence (92.6%) of a high oedema index compared with those with normal muscle mass (28.2%). This observation indicates that individuals with HIV who experience reduced muscle mass is commonly accompanied with abnormal fluid retention within the body. CONCLUSIONS: Antiretroviral medication types, specifically Zidovudine, BMI and NRI can be independent risk factors for low muscle mass in men with HIV. These factors, along with BMI, could be used conveniently to predict low muscle mass. Furthermore, the association between the oedema index and muscle mass suggests that observing signs of oedema may indicate a risk of low muscle mass in PLWH.

2.
Lipids Health Dis ; 23(1): 232, 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39080674

RESUMEN

OBJECTIVE: To investigate how antiretroviral therapy (ART) regimens and body mass index (BMI) interact to affect triglyceride (TG) levels in people living with HIV (PLWH). METHODS: This research involved 451 men living with HIV for cross-sectional analysis, and 132 underwent follow-up assessments in 2021 and 2023. Multivariate logistic regression identified key factors, while covariance regression models assessed interactions between ART regimens and BMI on TG levels. RESULTS: The result of this cross-sectional study indicated that advanced AIDS (acquired immune deficiency syndrome) stage (OR = 2.756, P = 0.003), higher BMI (OR = 1.131, P = 0.003), and waist-hip ratio (WHR, OR = 44.684, P = 0.019) are closely associated with high triglyceride levels. Additionally, regimens containing zidovudine (AZT) (OR = 3.927, P < 0.001) or protease inhibitors/integrase strand transfer inhibitors (PI/INSTI) (OR = 5.167, P < 0.001) were significantly linked to hypertriglyceridemia. Cross-sectional and longitudinal analyses from 2021 to 2023 emphasized that changes in BMI interact with antiretroviral treatment regimens to affect TG levels in PLWH (Pinteraction < 0.05). Especially in the AZT-based drug regimen, the correlation between BMI and TG is more prominent. CONCLUSION: The interaction between ART regimens and BMI influences TG levels in PLWH, indicating that weight management is crucial for reducing the risk of hypertriglyceridemia in this population.


Asunto(s)
Índice de Masa Corporal , Infecciones por VIH , Triglicéridos , Zidovudina , Humanos , Masculino , Triglicéridos/sangre , Estudios Transversales , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/sangre , Estudios Longitudinales , Adulto , Persona de Mediana Edad , Zidovudina/uso terapéutico , Fármacos Anti-VIH/uso terapéutico , Relación Cintura-Cadera , Hipertrigliceridemia/sangre , Terapia Antirretroviral Altamente Activa
4.
Fitoterapia ; 177: 106088, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38897245

RESUMEN

Ligularia fischeriTurcz. is a medicinal plant for the treatment of inflammation in China and Korea. Its chemical components in anti-sepsis activity and the related molecular mechanisms remain unknown yet. In this study, two undescribed eremophilane sesquiterpenoids fischerins A (1) and B (2), together with 8 known sesquiterpenoid derivatives (3-10), were isolated from the whole plant of L. fischeri. Their structures were identified by detailed spectroscopic and ECD analyses. 3-Oxo-8-hydroxyeremophila-1,7(11)-dien-12,8-olide (6) showed the most inhibitory effect on NO production in LPS-stimulated RAW 264.7 cells with the IC50 value of 6.528 µM. Meanwhile, compound 6 also decreased the mRNA expression of pro-inflammatory factors IFN-γ, IL-1ß, IL-6 and TNF-α via downregulating NF-κB signaling pathway in vitro. Furthermore, compound 6 reduced the mortality, murine sepsis score, the serum TNF-α level and organic damage in a mouse model of sepsis. These findings indicated that compound 6 possessed the potent anti-inflammatory activity and had the potential as a promising drug candidate for sepsis therapy.


Asunto(s)
Antiinflamatorios , Asteraceae , FN-kappa B , Sepsis , Sesquiterpenos , Animales , Ratones , Sesquiterpenos/farmacología , Sesquiterpenos/aislamiento & purificación , Asteraceae/química , Antiinflamatorios/farmacología , Antiinflamatorios/aislamiento & purificación , Estructura Molecular , Células RAW 264.7 , Sepsis/tratamiento farmacológico , FN-kappa B/metabolismo , Masculino , Óxido Nítrico/metabolismo , Fitoquímicos/farmacología , Fitoquímicos/aislamiento & purificación , China , Citocinas/metabolismo
5.
J Ethnopharmacol ; 332: 118328, 2024 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-38734391

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Jiegeng decoction (JGD), consisting of Glycyrrhizae Radix et Rhizoma and Platycodonis Radix at the ratio of 2:1, is a classical Chinese medicine prescription firstly recorded in "Treatise on Febrile Diseases". JGD has been extensively utilized to treat sore throat and lung diseases for thousands of years in China. However, the pharmacological effect and mechanism of JGD on acute pharyngitis (AP) remain unclear. AIM OF THE STUDY: Our research aimed to reveal the pharmacological effect of JGD on AP and its potential mechanisms. MATERIALS AND METHODS: The chemical components of JGD were analyzed based on the UPLC-MS analysis. The anti-inflammatory effect of JGD was evaluated by NO production using the Griess assay in RAW 264.7 cells. The mRNA expression of iNOS, IL-1ß, IL-10, TNF-α, IL-6 and MCP-1 was determined by qRT-PCR in vitro. A 15% ammonia-induced AP model was established. The histopathology, the inflammatory cytokines IL-6 and MCP-1 in serum and the apoptosis-related genes caspease-8 and caspease-3 were determined by H&E staining, ELISA and qRT-PCR, respectively. The expression levels of p-p65, p65, p-JNK, JNK, p-p38, p38, p-ERK1/2, ERK1/2, and COX2 were measured through western blotting. RESULTS: Nine compounds, including liquiritin, liquiritin apiosde, liquiritigenin, platycodin D, platycoside A, licorice saponin J2, licorice saponin G2, glycyrrhizic acid, and licochalcone A, were identified. JGD significantly inhibited NO production and regulated the mRNA expression levels of cytokines in LPS-stimulated RAW 264.7 cells. The results of in vivo experiments confirmed that JGD ameliorated AP through improving the pathological state of pharyngeal tissue, decreasing the serum levels of IL-6 and MCP-1 and preventing the tissue mRNA expression of caspease-8 and caspease-3. Furthermore, JGD also inhibited the NF-κB and MAPK pathways in the AP model. CONCLUSIONS: This study suggested that JGD could alleviate AP through its anti-inflammation via NF-κB and MAPK pathways, which supported the traditional application of JGD for the treatment of throat diseases.


Asunto(s)
Antiinflamatorios , Citocinas , Medicamentos Herbarios Chinos , FN-kappa B , Faringitis , Animales , Ratones , Células RAW 264.7 , Faringitis/tratamiento farmacológico , FN-kappa B/metabolismo , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Antiinflamatorios/farmacología , Citocinas/metabolismo , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Masculino , Enfermedad Aguda , Transducción de Señal/efectos de los fármacos
6.
Chem Biol Interact ; 397: 111083, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38821455

RESUMEN

Lung cancer stem cells (CSCs) drive continuous cancer growth and metastatic dissemination; thus, there is an urgent requirement to acquire effective therapeutic strategies for targeting lung CSCs. Diallyl trisulfide (DATS), a garlic organosulfide, possesses suppressive potential in lung cancer; however, its underlying mechanism is still unclear. In this study, we identified DATS as a pyroptosis inducer in lung cancer cells. DATS-treated A549 and H460 cells exhibited pyroptotic cell death, with characteristic large bubbles appearing on their plasma membrane and LDH release. DATS induced cell death, arrested the cell cycle at the G2/M phase, and inhibited colony formation in lung cancer cells. Meanwhile, we found that DATS significantly suppressed the malignant features by impairing lung CSC-like properties, including sphere formation ability, CD133 positive cell number, and lung CSCs marker expression. Mechanistically, DATS induced cell pyroptosis via increasing the expression of NLRP3, ASC, Pro Caspase 1, Cleaved Caspase 1, GSDMD, GSDMD-N, and IL-1ß. The verification experiments showed that the effects of DATS on pyroptosis and lung CSC-like properties were weakened after Caspase 1 inhibitor VX-765 treatment, indicating that DATS activated NLRP3 inflammasome-mediated pyroptosis by targeting Caspase 1 in lung cancer cells. Moreover, DATS increased ROS overproduction and mitochondrial dysfunction, which contributed to DATS-induced pyroptosis of lung cancer cells. NAC treatment reversed the effects of DATS on pyroptosis and CSC-like properties. In vivo experiment further confirmed that DATS restrained tumor growth. Together, our results suggest that DATS promotes pyroptosis and impairs lung CSC-like properties by activating ROS/Caspase 1 signaling pathway, thereby retarding lung cancer progression.


Asunto(s)
Compuestos Alílicos , Caspasa 1 , Neoplasias Pulmonares , Células Madre Neoplásicas , Piroptosis , Especies Reactivas de Oxígeno , Transducción de Señal , Sulfuros , Piroptosis/efectos de los fármacos , Compuestos Alílicos/farmacología , Sulfuros/farmacología , Humanos , Especies Reactivas de Oxígeno/metabolismo , Caspasa 1/metabolismo , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Transducción de Señal/efectos de los fármacos , Células Madre Neoplásicas/efectos de los fármacos , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Animales , Línea Celular Tumoral , Ratones , Ratones Desnudos , Ratones Endogámicos BALB C , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Células A549
7.
Phytochemistry ; 217: 113927, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37956887

RESUMEN

Eleven undescribed labdane diterpenoids, sibiricusins K-U, and seven known analogues were obtained from the MeOH extract of the aerial parts of Leonurus sibiricus. The structures of the compounds were established by detailed spectroscopic data analysis, single-crystal X-ray diffraction analysis and ECD calculations. Among them, sibiricusins L-N featured a rare α, ß-unsaturated-γ-lactam moiety. Fourteen of the isolates were evaluated for their anti-inflammatory effect on the production of NO in LPS-induced RAW264.7 cells through Griess assay. Sibiricusin O displayed the strongest activity with an IC50 value of 9.0 ± 1.7 µM.


Asunto(s)
Diterpenos , Leonurus , Leonurus/química , Estructura Molecular , Antiinflamatorios/farmacología , Diterpenos/química , Componentes Aéreos de las Plantas/química
8.
Medicine (Baltimore) ; 102(34): e34527, 2023 Aug 25.
Artículo en Inglés | MEDLINE | ID: mdl-37653749

RESUMEN

BACKGROUND: Transarterial chemoembolization (TACE) consists of conventional TACE (cTACE) and drug-eluting beads TACE (DEB-TACE). The benefits of the 2 treatments remain controversial. We conduct this meta-analysis to assess the efficacy and safety of the 2 methods for the patients with unresectable hepatocellular carcinoma. METHODS: In order to get a sound conclusion, we did thorough search all relevant studies with clear and stringent keyword criteria on the main databases. Objective tumor response rate, overall survival (OS) rate and adverse events were calculated and analyzed by RevMan 5.3 software. The random-effects or fixed-effects model was applied to pool the estimates according to Cochran Q test and I2 statistics. RESULTS: Twenty-four studies involving 2987 patients were eligible. DEB-TACE significantly improved objective tumor response rate (OR) (risk ratio [RR] = 1.27, 95% confidence interval [CI] [1.08, 1.48]; P = .003). While as for 1-year, 2-year, 3-year, 5-year OS rates, there were no evidences to indicate that DEB-TACE was significantly better than cTACE (RR = 1.05, 95% CI [0.99, 1.11]; P = .08), (RR = 1.02, 95% CI [0.93, 1.11]; P = .68), (RR = 0.92, 95% CI [0.77, 1.10]; P = .37), (RR = 0.92, 95% CI [0.47, 1.80]; P = .81), respectively. Adverse events rate (AE) was also similar in both groups (RR = 1.11, 95% CI [0.99,1.26]; P = .08). CONCLUSION: This meta-analysis demonstrates that DEB-TACE is not superior than cTACE regarding to OS and AE. However, DEB-TACE still be considered to provide a better objective tumor response rate for patients with unresectable hepatocellular carcinoma.


Asunto(s)
Carcinoma Hepatocelular , Quimioembolización Terapéutica , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/terapia , Procedimientos Quirúrgicos Vasculares , Bases de Datos Factuales
9.
Mol Carcinog ; 62(11): 1673-1685, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37477518

RESUMEN

Gastric cancer is one of the deadliest malignant tumors, and half of the patients develop recurrences or metastasis within 5 years after eradication therapy. Cancer stem cells (CSCs) are considered to be important in this progress. The sonic hedgehog (SHH) pathway plays an important role in the maintenance of gastric CSCs characteristics. The p63 proteins are vital transcription factors belonging to the p53 family, while their functions in regulating CSCs remain unclear. The preventive effects of dietary diallyl trisulfide (DATS) against human gastric cancer have been verified. However, whether DATS can target gastric CSCs are poorly understood. Here, we investigated the role of ΔNp63/SHH pathway in gastric CSCs and the inhibitory effect of DATS on gastric CSCs via ΔNp63/SHH pathway. We found that ΔNp63 was upregulated in serum-free medium cultured gastric tumorspheres compared with the parental cells. Overexpression of ΔNp63 elevated the self-renewal capacity and CSC markers' levels in gastric sphere-forming cells. Furthermore, we found that ΔNp63 directly bound to the promoter region of Gli1, the key transcriptional factor of SHH pathway, to enhance its expression and to activate SHH pathway. In addition, it was revealed that DATS effectively inhibited gastric CSC properties both in vitro and in vivo settings. Activation of SHH pathway attenuated the suppressive effects of DATS on the stemness of gastric cancer. Moreover, DATS suppression of gastric CSC properties was also diminished by ΔNp63 upregulation through SHH pathway activation. These findings illustrated the role of ΔNp63/SHH pathway in DATS inhibition of gastric cancer stemness. Taken together, the present study suggested for the first time that DATS inhibited gastric CSCs properties by ΔNp63/SHH pathway.


Asunto(s)
Proteínas Hedgehog , Neoplasias Gástricas , Humanos , Proteínas Hedgehog/metabolismo , Proteínas Hedgehog/farmacología , Neoplasias Gástricas/patología , Transducción de Señal , Factores de Transcripción/metabolismo , Células Madre Neoplásicas/patología , Línea Celular Tumoral
10.
Phytochemistry ; 214: 113802, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37506992

RESUMEN

Nine undescribed labdane diterpenoids (1-9) and one undescribed ent-halimane diterpenoid (10) were isolated from the aerial parts of Leonurus sibiricus, together with four known analogues (11-14) during our searching for naturally occurring antitumor agents. Their structures were established by detailed spectroscopic analyses and electronic circular dichroism analysis. Compound 4 possessed a rare 10-epi labdane scaffold. All compounds except 5 were evaluated for their inhibitory activities against interleukin (IL)-6-stimulated signal transducer and activator of transcription (STAT3) expression using a luciferase reporter assay. Compound 1 showed the most inhibitory effect with the IC50 value 20.31 µM. Compound 1 inhibited the activation of JAK2/STAT3 signal pathway through binding to Gln326 of STAT3 in CNE cells. The antiproliferative evaluation of compound 1 against CNE, CAL-27, A549 and PANC-1 cells demonstrated that CNE cells were the most sensitive to 1. Furthermore, compound 1 showed moderate efficacy in inhibiting cell migration, invasion, and epithelial-mesenchymal transition in CNE cells. In addition, compound 1 also promoted ferroptosis in CNE cells in a dose-dependent manner. These results suggest that compound 1 might be a potential candidate lead for treating nasopharyngeal carcinoma.


Asunto(s)
Diterpenos , Leonurus , Dicroismo Circular , Diterpenos/farmacología , Diterpenos/química , Leonurus/química , Estructura Molecular , Factor de Transcripción STAT3/antagonistas & inhibidores
11.
Phytochemistry ; 214: 113797, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37495182

RESUMEN

Two undescribed polyoxygenated seco-cyclohexene derivatives named macclureins A and B, and three undescribed polyoxygenated cyclohexene derivatives macclureins C-E, together with 15 known analogues were isolated from the twigs and leaves of Uvaria macclurei. Their structures were established by extensive spectroscopic and circular dichroism analyses. Macclurein C is a chlorinated polyoxygenated cyclohexene. All isolates were evaluated for their anti-inflammatory activities on NO generation in the LPS-stimulated RAW 264.7 cells. (-)-Zeylenone showed the most potent effect against NO production with the IC50 value of 20.18 µM. Meanwhile, (-)-zeylenone also decreased the mRNA expression of pro-inflammatory factors IFN-γ, iNOS, IL-6 and TNF-α via downregulating NF-κB signaling pathway. Further in vivo experiments using a mouse model of sepsis showed that (-)-zeylenone significantly alleviated sepsis severity by measuring weight, murine sepsis score, survival rate and the serum levels of pro-inflammatory factors TNF-α and IL-6.

14.
Mol Immunol ; 158: 10-21, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-37087900

RESUMEN

Human amniotic mesenchymal stem cells (hAMSCs) have attracted considerable attention as a promising regenerative therapy. Many studies reported that the conditioned medium of hAMSCs (AM-CM) exerted anti-inflammatory and immunomodulatory functions, while its underlying mechanism is poorly understood. In this study, we first confirmed that AM-CM (25%, 50%, 100%) was optimal for anti-inflammation at 24 h. Lipopolysaccharide (LPS)-induced alteration of cell morphology, the decrease of cell proliferation, and the upregulation of cell apoptosis were significantly reversed in AM-CM-treated THP-1 cells. 25% and 50% AM-CM significantly decreased LPS-induced intracellular reactive oxygen species (ROS) production and proinflammatory cytokines secretion. Mechanistically, we found that AM-CM treatment suppressed LPS-induced activation of MAPK and NF-κB pathways by inhibiting CD14/TLR4 in THP-1 cells. Meanwhile, activation of NLRP3 inflammasome was also dose-dependently attenuated by AM-CM treatment. Thus, AM-CM may exert positive influences on the inflammation microenvironment and provide a novel strategy for improving tissue regeneration.


Asunto(s)
Lipopolisacáridos , Células Madre Mesenquimatosas , Humanos , Lipopolisacáridos/farmacología , Lipopolisacáridos/metabolismo , Monocitos/metabolismo , Medios de Cultivo Condicionados/farmacología , Medios de Cultivo Condicionados/metabolismo , Receptor Toll-Like 4/metabolismo , Citocinas/metabolismo , Transducción de Señal , Inflamación/metabolismo , FN-kappa B/metabolismo , Factores Inmunológicos/farmacología , Antiinflamatorios/farmacología , Células Madre Mesenquimatosas/metabolismo
15.
Phytother Res ; 37(7): 2995-3008, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-36866538

RESUMEN

Resveratrol (RES) has various pharmacological bioactivities and its anticancer effects in lung cancer have been proven. However, the underlying mechanisms of action of RES in lung cancer remain unclear. This study focused on Nrf2-mediated antioxidant systems in RES-treated lung cancer cells. A549 and H1299 cells were treated with various concentrations of RES at different times. RES decreased cell viability, inhibited cell proliferation, and increased the number of senescent and apoptotic cells in a concentration- and time-dependent manner. Moreover, RES-induced lung cancer cell arrest at the G1 phase was accompanied by changes in apoptotic proteins (Bax, Bcl-2, and cleaved caspase 3). Furthermore, RES induced a senescent phenotype along with changes in senescence-related markers (senescence-associated ß-galactosidase activity, p21, and p-γH2AX). More importantly, with prolonged exposure time and increased exposure concentration, intracellular reactive oxygen species (ROS) continuously accumulated, resulting in a decrease in Nrf2 and its downstream antioxidant response elements, including CAT, HO-1, NQO1, and SOD1. Meanwhile, RES-induced ROS accumulation and cell apoptosis were reversed by N-acetyl-l-cysteine treatment. Taken together, these results suggest that RES disturb lung cancer cellular homeostasis by destroying the intracellular antioxidant pool to increase ROS production. Our findings provide a new perspective on RES intervention in lung cancer.


Asunto(s)
Antioxidantes , Neoplasias Pulmonares , Humanos , Antioxidantes/farmacología , Resveratrol/farmacología , Especies Reactivas de Oxígeno/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Apoptosis , Senescencia Celular , Línea Celular Tumoral
16.
Chem Biodivers ; 20(5): e202300220, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-36999317

RESUMEN

Two new 1,10-seco-eudesmanolides (1 and 2) were isolated from the flowers of Inula japonica together with two eudesmanolide analogs (3 and 4) and two monoterpene derivatives (5 and 6). Their structures were established on the basis of detailed spectroscopic analyses and electronic circular dichroism data. All isolates were evaluated for their antiproliferative activities against human hepatocarcinoma HepG2 and SMMC-7721 cells. Japonipene B (3) exhibited the most potent effect with the IC50 values of 14.60±1.62 and 22.06±1.34 µM against HepG2 and SMMC-7721 cells, respectively. Furthermore, japonipene B (3) showed significant efficacies of arresting the cell cycle at the S/G2-M stages, inducing mitochondria-mediated apoptosis, and inhibiting cell migration in HepG2 cells.


Asunto(s)
Antineoplásicos , Inula , Humanos , Inula/química , Terpenos/farmacología , Terpenos/análisis , Estructura Molecular , Flores/química
17.
Ecotoxicol Environ Saf ; 252: 114605, 2023 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-36753971

RESUMEN

BACKGROUND: The omnipresence of human phthalate (PAE) exposure is linked to various adverse health issues, including breast cancer. However, the effects of low-dose PAE exposure on breast cancer stem cells (BCSCs) and the underlying mechanism remain unexplored. METHODS: BCSCs from breast cancer cell lines (MDA-MB-231 and MCF-7) were enriched using a tumorsphere formation assay. Gene and protein expression was detected by measurement of quantitative real-time reverse transcription PCR, western blot, and immunofluorescence assays. Transient transfection assays were used to evaluate the involvement of Gli1, a signaling pathway molecule and ΔNp63α, an oncogene in influencing the PAE-induced characteristics of BCSCs. RESULTS: PAE (butylbenzyl phthalate, BBP; di-butyl phthalate, DBP; di-2-ethylhexyl phthalate, DEHP) exposure of 10-9 M significantly promoted the tumorsphere formation ability in BCSCs. Breast cancer spheroids with a 10-9 M PAE exposure had higher levels of BCSC marker mRNA and protein expression, activated sonic hedgehog (SHH) pathway, and increased mRNA and protein levels of an oncogene, ΔNp63α. Furthermore, suppression of the SHH pathway attenuated the effects of PAEs on BCSCs. And the overexpression of ΔNp63α enhanced PAE-induced characteristics of BCSCs, while low expression of ΔNp63α inhibited the promotion effects of PAEs on BCSCs and the SHH pathway. CONCLUSION: Low-dose PAE exposure promoted the stem cell properties of BCSCs in a ΔNp63α- and SHH-dependent manner. The influence of low-dose exposure of PAEs and its relevance for the lowest observed effect concentrations requires further investigation, and the precise underlying mechanism needs to be further explored.


Asunto(s)
Neoplasias de la Mama , Proteínas Hedgehog , Humanos , Femenino , Proteínas Hedgehog/genética , Proteínas Hedgehog/metabolismo , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Transducción de Señal , Oncogenes , Células Madre Neoplásicas/metabolismo , Línea Celular Tumoral
18.
Phytomedicine ; 112: 154687, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36804756

RESUMEN

BACKGROUND: Hepatocellular carcinoma has high ability of vascular invasion and metastasis. Vasculogenic mimicry (VM) is closely related to the metastasis and recurrence of hepatocellular carcinoma (HCC). According to previous research, Chloranthus henryi has anti-tumor effect, but its molecular mechanism in the treatment of HCC has not yet been stated. PURPOSE: In our study, we aimed to investigate the effect of the extract of Chloranthus henryi in HCC and its target and molecular mechanism. We hoped to explore potential drugs for HCC treatment. STUDY DESIGN/METHODS: In this study, we isolated a chalcone compound from Chloranthus henryi, compound 4, identified as flavokawain A (FKA). We determined the anti-HCC effect of FKA by MTT and identified the target of FKA by molecular docking and CETSA. Hepatoma cells proliferation, migration, invasion, and VM formation were examined using EDU, wound healing, transwell, vasculogenic mimicry, and IF. WB, RT-PCR, and cell transfection were used to explore the mechanism of FKA on hepatoma cells. Tissue section staining is mainly used to demonstrate the effect of FKA on HCC in vivo. RESULTS: We confirmed that FKA can directly interact with CXCL12 and HCC proliferation, migration, invasion, and VM formation were all inhibited through reversing the EMT progress in vitro and in vivo through the PI3K/Akt/NF-κB signaling pathway. Additionally, by overexpressing and knocking down CXCL12, we got the same results. CONCLUSION: FKA attenuated proliferation, invasion and metastatic and reversed EMT in HCC via PI3K/Akt/HIF-1α/NF-κB/Twist1 pathway by targeting CXCL12. This study proposed that FKA may be a candidate drug and prospective strategy for HCC therapy.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patología , Proteínas Proto-Oncogénicas c-akt , FN-kappa B , Simulación del Acoplamiento Molecular , Fosfatidilinositol 3-Quinasas , Neoplasias Hepáticas/patología , Línea Celular Tumoral , Neovascularización Patológica/tratamiento farmacológico , Neovascularización Patológica/metabolismo , Movimiento Celular , Transición Epitelial-Mesenquimal , Quimiocina CXCL12
19.
Sci Rep ; 13(1): 1147, 2023 01 20.
Artículo en Inglés | MEDLINE | ID: mdl-36670177

RESUMEN

The aim of the present study was to investigate the role of endoplasmic reticulum (ER) stress in bisphenol A (BPA) - induced hepatic lipid accumulation as well as the protective effects of Sulforaphane (SFN) in this process. Human hepatocyte cell line (LO2) and C57/BL6J mice were used to examine BPA-triggered hepatic lipid accumulation and the underlying mechanism. Hepatic lipid accumulation, triglycerides (TGs) levels, the expression levels of lipogenesis-related genes and proteins in the ER stress pathway were measured. It was revealed that BPA treatment increased the number of lipid droplets, the levels of TG and mRNAs expression of lipogenesis-related genes, and activated the ER stress pathway. These changes were inhibited by an ER stress inhibitor 4-phenylbutyric acid. SFN treatment abrogated BPA-altered hepatic lipid metabolism and ameliorated BPA-induced ER stress-related markers. Together, these findings suggested that BPA activated ER stress to promote hepatic lipid accumulation, and that SFN reversed those BPA effects by alleviating ER stress.


Asunto(s)
Hígado , Enfermedad del Hígado Graso no Alcohólico , Humanos , Animales , Ratones , Hígado/metabolismo , Metabolismo de los Lípidos , Estrés del Retículo Endoplásmico , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Lípidos/farmacología
20.
Toxicology ; 484: 153408, 2023 01 15.
Artículo en Inglés | MEDLINE | ID: mdl-36565802

RESUMEN

As the use of bisphenol A (BPA) has been restricted in consumer products, bisphenol S (BPS) is one major alternative to BPA for various materials, leading to growing concerns about its health risks in human beings. However, little is known about the toxic effects of BPS on bone health. We employed human bone marrow mesenchymal stem cells (hBMSCs) for the in vitro assessment of BPS on cell proliferation, differentiation, and self-renewal. Our study revealed that BPS at concentrations of 10-10-10-7 M increased cell viability but induced the morphological changes of hBMSCs. Moreover, BPS decreased ROS generation and increased Nrf2 expression. Furthermore, BPS not only activated ERα/ß expression but also increased ß-catenin expression and induced the replicative senescence of hBMSCs. Furthermore, we found that the upregulation of ß-catenin induced by BPS was mediated, in part, by ER signaling. Overall, our results suggested BPS exposure caused the homeostatic imbalance of hBMSCs.


Asunto(s)
Células Madre Mesenquimatosas , beta Catenina , Humanos , Densidad Ósea , Huesos , Receptores de Estrógenos , Compuestos de Bencidrilo/toxicidad
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