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In recent years, the search for natural compounds with therapeutic properties has gained momentum, with marine organisms emerging as rich sources of bioactive substances [...].
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The standard of care for prostate cancer (PCa) is androgen deprivation therapy (ADT). Although hormone-sensitive PCa is curable by ADT, most conditions progress to castration-resistant prostate cancer (CRPCa) and metastatic CRPCa (mCRPCa). Front-line docetaxel has been administered to patients with CRPCa and mCRPCa. Nevertheless, docetaxel resistance after half a year of therapy has emerged as an urgent clinical concern in patients with CRPCa and mCRPCa. We verified the mechanism by which docetaxel-resistant PCa cells (DU/DX50) exhibited significant cell migration and expression of malignant tumor-related proteins. Our study shows that the biological activity of fucoidan has an important application for docetaxel-resistant PCa cells, inhibiting IL-1R by binding to P-selectin and reducing the expression levels of NF-κB p50 and Cox2 in this metastasis-inhibiting signaling pathway. Furthermore, the combined treatment of fucoidan and docetaxel showed significant anticancer and synergistic effects on the viability of DU/DX50 cells, which is relevant for overcoming the current limitations and improving treatment outcomes. Overall, fucoidan-based combination chemotherapy may exert beneficial effects and facilitate the treatment of docetaxel-resistant PCa.
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Selectina-P , Neoplasias de Próstata Resistentes à Castração , Antagonistas de Androgênios/uso terapêutico , Androgênios , Ciclo-Oxigenase 2 , Docetaxel/farmacologia , Docetaxel/uso terapêutico , Humanos , Masculino , NF-kappa B , Metástase Neoplásica/tratamento farmacológico , Polissacarídeos , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológicoRESUMO
The activation of hepatic stellate cells (HSCs) is a key component of liver fibrosis. Two antifibrosis pathways have been identified, the reversion to quiescent-type HSCs and the clearance of HSCs through apoptosis. Lipopolysaccharide- (LPS-) induced HSCs activation and proliferation have been associated with the development of liver fibrosis. We determined the pharmacological effects of wild bitter melon (WM) on HSC activation following LPS treatment and investigated whether WM treatment affected cell death pathways under LPS-treated conditions, including ferroptosis. WM treatment caused cell death, both with and without LPS treatment. WM treatment caused reactive oxygen species (ROS) accumulation without LPS treatment and reversed the decrease in lipid ROS production in HSCs after LPS treatment. We examined the effects of WM treatment on fibrosis, endoplasmic reticulum (ER) stress, inflammation, and ferroptosis in LPS-activated HSCs. The western blotting analysis revealed that the WM treatment of LPS-activated HSCs induced the downregulation of the connective tissue growth factor (CTGF), α-smooth muscle actin (α-SMA), integrin-ß1, phospho-JNK (p-JNK), glutathione peroxidase 4 (GPX4), and cystine/glutamate transporter (SLC7A11) and the upregulation of CCAAT enhancer-binding protein homologous protein (CHOP). These results support WM as an antifibrotic agent that may represent a potential therapeutic solution for the management of liver fibrosis.
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The aim of this study was to develop a macrophage-targeted nanoparticle composed of hyaluronan/fucoidan complexes with polyethylene glycol-gelatin to encapsulate and deliver epigallocatechin-3-gallate (EGCG), a compound that can regulate macrophage activation and pro-inflammatory mediator production. We show that our nanoparticles can successfully bond to macrophages and deliver more EGCG than an EGCG solution treatment, confirming the anti-inflammatory effects of these nanoparticles in lipopolysaccharide-stimulated macrophages. The prepared nanoparticles were established with a small mean particle size (217.00 ± 14.00 nm), an acceptable polydispersity index (0.28 ± 0.07), an acceptable zeta potential value (-33.60 ± 1.30 mV), and a high EGCG loading efficiency (52.08% ± 5.37%). The targeting abilities of CD44 binding were increased as the hyaluronan concentration increased and decreased by adding a competitor CD44 antibody. Moreover, we found that fucoidan treatment significantly reduced macrophage migration after lipopolysaccharide treatment in a dose-responsive manner. In summary, we successfully created macrophage-targeted nanoparticles for effective targeted delivery of EGCG, which should aid in the development of future anti-inflammatory drugs against macrophage-related diseases.
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Catequina/análogos & derivados , Sistemas de Liberação de Medicamentos , Ácido Hialurônico/química , Inflamação/tratamento farmacológico , Macrófagos/efeitos dos fármacos , Nanopartículas/administração & dosagem , Polissacarídeos/química , Animais , Catequina/química , Catequina/farmacologia , Movimento Celular , Portadores de Fármacos/química , Receptores de Hialuronatos/metabolismo , Inflamação/induzido quimicamente , Lipopolissacarídeos , Macrófagos/metabolismo , Camundongos , Nanopartículas/química , Células RAW 264.7RESUMO
Phthalates are widely used plasticizers that can cause endocrine disruption, mutagenicity, and carcinogenic effects and can contaminate food through various pathways. Investigations are scanty on phthalate pollution of livestock and poultry meat and their dietary exposure to humans. The present study assessed residual levels of phthalates in unpackaged pork (30 samples) and unpackaged chicken (30 samples) and their relevance to meat consumption and health risks in the Taiwanese population. Phthalate quantity was assessed by liquid chromatography-tandem mass spectrometry; the materials included diisononyl phthalate, diisodecyl phthalate, benzyl butyl phthalate, di-2-ethylhexyl phthalate (DEHP), and di-n-butyl phthalate. The Taiwan Food and Drug Administration (TFDA) has established values of tolerable daily intake (TDI) for the five phthalates. The major compound detected was DEHP, which ranged from 0.62 to 0.80 mg/kg in two pork samples, and 0.42-0.45 mg/kg in three chicken samples. Collectively, 8.33% of the phthalate-residue-containing samples tested positive for DEHP. The concentrations of DEHP were lower than the screening value of 1.0 mg/kg, as defined by the TFDA. Health risk was calculated as the estimated daily intake (DI) for any likely adverse effects; the DI of DEHP residues was <1% of the TDI value. The estimated risk was insignificant and considered to be safe, indicating that there is no risk to the health of Taiwanese population due to meat consumption. However, it is suggested that a phthalate monitoring program in meat should be instituted for any possible effects in future on human health.
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Poluentes Ambientais/análise , Análise de Alimentos , Ácidos Ftálicos/análise , Carne de Porco/análise , Aves Domésticas , Animais , Cromatografia Líquida , Humanos , Taiwan , Espectrometria de Massas em TandemRESUMO
Amniotic fluid embolism occurs rarely but is a leading cause of maternal mortality. Regardless of emergent supportive medical treatment, it is associated with a very high mortality rate. Here, we present the case of a 33-year-old pregnant woman with amniotic fluid embolism, who sustained cardiac arrest and was rescued with early application of extracorporeal membrane oxygenation. The management of amniotic fluid embolism is to initially focus on rapid cardiopulmonary stabilization. Hemodynamic decompensation may be transient and recoverable within a few hours. Early application of extracorporeal membrane oxygenation should be considered in patients who are unresponsive to medical therapy before severe organ damage supervenes.
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Embolia Amniótica/terapia , Oxigenação por Membrana Extracorpórea , Adulto , Embolia Amniótica/fisiopatologia , Feminino , Hemodinâmica , Humanos , GravidezRESUMO
BACKGROUND: Epidural patient-controlled analgesia (EPCA) and intravenous patient-controlled analgesia (IVPCA) have been used widely in parturients after cesarean section. Although many studies have demonstrated the safety and effectiveness of both EPCA and IVPCA, their effects on bowel activity of patients who have undergone cesarean section delivery have not yet been investigated. The purpose of this study was to compare the effect of EPCA and IVPCA on bowel activity after cesarean section. METHODS: We collected data from 726 parturients who consented to receive either EPCA or IVPCA for postoperative analgesia following cesarean section delivery. All patients used postoperative PCA for at least 2 days. The analgesic solution for EPCA was 0.05% bupivacaine plus fentanyl (3 microg/mL), and that for IVPCA was 0.1% morphine. The patients were assessed by visual analog pain scale (VAS) scores at rest and in a dynamic state, time to first flatus passage after the surgery, and overall satisfaction after completion of the PCA course. Student's t test was used to determine intergroup differences. RESULTS: There were statistically significant differences between the EPCA and IVPCA groups in the time to first flatus passage, overall satisfaction and VAS scores at rest and in a dynamic state. Patients in the EPCA group had a shorter time to first flatus passage, higher overall satisfaction and lower VAS scores. In addition, regional anesthesia offered an apparently shorter time to first flatus passage in comparison with general anesthesia. CONCLUSION: PCA is safe and effective in alleviating postoperative pain following cesarean section. EPCA offers a faster return of bowel activity, lower VAS scores, and better patient satisfaction than IVPCA.