RESUMEN
Emerging evidence has provided considerable insights into the integral function of reprogramming fatty acid metabolism in the carcinogenesis and progression of endometrial cancer. Linoleic acid, an essential fatty acid with the highest consumption in the Western diet regimen, has shown pro-tumorigenic or anti-tumorigenic effects on tumor cell growth and invasion in multiple types of cancer. However, the biological role of linoleic acid in endometrial cancer remains unclear. In the present study, we aimed to investigate the functional impact of linoleic acid on cell proliferation, invasion, and tumor growth in endometrial cancer cells and in a transgenic mouse model of endometrial cancer. The results showed that Linoleic acid significantly inhibited the proliferation of endometrial cancer cells in a dose-dependent manner. The treatment of HEC-1A and KLE cells with linoleic acid effectively increased intracellular reactive oxygen species (ROS) production, decreased mitochondrial membrane potential, caused cell cycle G1 arrest, and induced intrinsic and extrinsic apoptosis pathways. The anti-invasive ability of linoleic acid was found to be associated with the epithelial-mesenchymal transition process in both cell lines, including the decreased expression of N-cadherin, snail, and vimentin. Furthermore, treatment of Lkb1fl/flp53fl/fl transgenic mice with linoleic acid for four weeks significantly reduced the growth of endometrial tumors and decreased the expression of VEGF, vimentin, Ki67, and cyclin D1 in tumor tissues. Our findings demonstrate that linoleic acid exhibits anti-proliferative and anti-invasive activities in endometrial cancer cell lines and the Lkb1fl/flp53fl/fl mouse model of endometrial cancer, thus providing a pre-clinical basis for future dietary interventions with linoleic acid in endometrial cancer.
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Neoplasias Endometriales , Ácido Linoleico , Humanos , Femenino , Ratones , Animales , Vimentina/metabolismo , Ácido Linoleico/farmacología , Ácido Linoleico/uso terapéutico , Línea Celular Tumoral , Proteína p53 Supresora de Tumor , Neoplasias Endometriales/tratamiento farmacológico , Neoplasias Endometriales/genética , Neoplasias Endometriales/metabolismo , Carcinogénesis , Proliferación CelularRESUMEN
IMPORTANCE: Porcine epidemic diarrhea virus (PEDV) is a pig coronavirus that causes severe diarrhea and high mortality in piglets, but as no effective drugs are available, this virus threatens the pig industry. Here, we found that the intestinal contents of specific pathogen-free pigs effectively blocked PEDV invasion. Through proteomic and metabolic analyses of the intestinal contents, we screened 10 metabolites to investigate their function and found that linoleic acid (LA) significantly inhibited PEDV replication. Further investigations revealed that LA inhibited viral replication and release mainly by binding with PEDV NSP5 to regulate the PI3K pathway and, in particular, inhibiting AKT phosphorylation. In vivo experiments illustrated that orally administered LA protected pigs from PEDV challenge and severe diarrhea. These findings provide strong support for exploring antiviral drugs for coronavirus treatment.
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Antivirales , Infecciones por Coronavirus , Diarrea , Ácido Linoleico , Virus de la Diarrea Epidémica Porcina , Enfermedades de los Porcinos , Animales , Infecciones por Coronavirus/tratamiento farmacológico , Infecciones por Coronavirus/veterinaria , Diarrea/tratamiento farmacológico , Diarrea/veterinaria , Ácido Linoleico/uso terapéutico , Fosfatidilinositol 3-Quinasas/metabolismo , Virus de la Diarrea Epidémica Porcina/fisiología , Proteómica , Porcinos , Enfermedades de los Porcinos/tratamiento farmacológico , Replicación Viral/efectos de los fármacos , Antivirales/uso terapéuticoRESUMEN
Natural medicines are promising platforms for competent topical treatment modalities benefiting the cosmetic implementation and proffering solutions to the current remedies. Therefore, the objective of this study was to formulate syringic acid (SA), well-known for its multilateral anti-inflammatory, antimicrobial and antioxidant potentials, in newly developed linoleic acid (LA) transferosomes as an anti-acne nano-form remedy. Herein, LA was incorporated in transferosomes owing to its antimicrobial effect and dermal penetrability. Comprehensive appraisal through physicochemical, antioxidant and dermal deposition investigations was conducted. Clinical assessment was also performed in acne patients and compared with the marketed product (Adapalene® gel). The relevant investigations of the optimum formula indicated stable vesicles with a small-sized diameter (147.46 nm), surface charge (-26.86 mV), spherical architecture, reasonable entrapment (76.63%), considerable antioxidant activity (IC50 = 11.1 µg/mL) and remarkable skin deposition (78.72%).More importantly, LA based transferosomes enclosing SA exhibited inflammation lessening in acne sufferers as manifested by greater reduction in the total count of the acne lesions reaching 79.5% in contrast to Adapalene® gel with only 18.7% reduction in acne lesions. Interestingly, no irritation and erythema were reported for the proposed transferosomes. Inclusively, the cosmetic formulation practice could reap benefits of the development of such vesicles.
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Acné Vulgar , Liposomas , Humanos , Liposomas/uso terapéutico , Ácido Linoleico/uso terapéutico , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Relevancia Clínica , Acné Vulgar/tratamiento farmacológico , Acné Vulgar/patología , Adapaleno , GelesRESUMEN
OBJECTIVES: Friedreich ataxia is (FRDA) an autosomal recessive neurodegenerative disorder associated with intrinsic oxidative damage, suggesting that decreasing lipid peroxidation (LPO) might ameliorate disease progression. The present study tested the ability of RT001, a deuterated form of linoleic acid (D2-LA), to alter disease severity in patients with FRDA in a double-blind placebo-controlled trial. METHODS: Sixty-five subjects were recruited across six sites and received either placebo or active drug for an 11-month study. Subjects were evaluated at 0, 4, 9, and 11 months, with the primary outcome measure being maximum oxygen consumption (MVO2) during cardiopulmonary exercise testing (CPET). A key secondary outcome measure was a composite statistical test using results from the timed 1-min walk (T1MW), peak workload, and MVO2. RESULTS: Forty-five subjects completed the protocol. RT001 was well tolerated, with no serious adverse events related to drug. Plasma and red blood cell (RBC) membrane levels of D2-LA and its primary metabolite deuterated arachidonic acid (D2-AA) achieved steady-state concentrations by 4 months. No significant changes in MVO2 were observed for RT001 compared to placebo. Similarly, no differences between the groups were found in secondary or exploratory outcome measures. Post hoc evaluations also suggested minimal effects of RT001 at the dosages used in this study. INTERPRETATIONS: The results of this study provide no evidence for a significant benefit of RT001 at the dosages tested in this Friedreich ataxia patient population.
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Ataxia de Friedreich , Ácido Linoleico , Humanos , Ataxia de Friedreich/tratamiento farmacológico , Ácido Linoleico/uso terapéutico , Ácidos Linoleicos/uso terapéutico , Caminata , Método Doble CiegoRESUMEN
Atrial fibrillation significantly increases the risk of thromboembolism and stroke. Wenxin Keli (WXKL) is a widely used Chinese patent medicine against arrhythmia but if it has antithrombotic activity is unknown. Since platelet activation is a critical factor in thrombosis and the key target for many antithrombotic drugs, this study aims to demonstrate the antithrombotic efficacy of WXKL. In vitro platelet activation experiments showed that WXKL significantly inhibited platelet adhesion and aggregation. The potential active monomers in WXKL were screened by in silico prediction and in vitro platelet aggregation/adhesion assays. From WXKL chemical fractions and more than 40 monomers, linoleic acid (LA) was identified as the strongest antiplatelet compound. Oral administration of WXKL (1.2 g/kg/day) and LA (50 mg/kg/day) for 7 days significantly improved FeCl3-induced carotid thrombus formation in ICR mice without prolonging bleeding time. Flow cytometry showed that both WXKL and LA inhibited the release of p-selectin after platelet activation. ELISA showed that WXKL and LA also inhibited the expression of 6-Keto-PGF1α in plasma of mice with thrombus, but had no obvious effect on the expression of TXB2. WXKL inhibited platelet activation by broadly inhibiting the phosphorylation of protein kinase B (Akt), mitogen-activated protein kinases (MAPKs) and phospholipase C (PLC) ß3. In contrast, LA only inhibited the phosphorylation of PLCß3. In conclusion, WXKL and its active component LA showed good antiplatelet and antithrombotic efficacy in vivo and in vitro. Mechanistically, the multicomponent Chinese medicine WXKL acts on multiple targets in the platelet activation pathway whereas its active monomer linoleic acid acts specifically on phospholipase C ß3.
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Fibrilación Atrial , Ácido Linoleico , Activación Plaquetaria , Trombosis , Animales , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Fibrinolíticos/farmacología , Ácido Linoleico/farmacología , Ácido Linoleico/uso terapéutico , Ratones , Ratones Endogámicos ICR , Selectina-P/efectos de los fármacos , Selectina-P/metabolismo , Activación Plaquetaria/efectos de los fármacos , Agregación Plaquetaria , Inhibidores de Agregación Plaquetaria/farmacología , Trombosis/tratamiento farmacológicoRESUMEN
As the most common subtype in ovarian malignancies, high-grade serous ovarian cancer (HGSOC) made less therapeutic progress in past decades due to the lack of effective drug-able targets. Herein, an effective linoleic acid (LA) and glucosamine (GlcN) hybrid (LA-GlcN) was synthesized for the treatment of HGSOC. The GlcN was introduced to recognize the glucose transporter 1 (GLUT 1) overexpressed in tumor cells to enhance the uptake of LA-GlcN, and the unsaturated LA was employed to trigger ferroptosis by iron-dependent lipid peroxidation. Since the iron content of HGSOC was â¼5 and 2 times, respectively, higher than that of the normal ovarian cells and low-grade serous ovarian cancer cells, these excess irons make them a good target to enhance the ferroptosis of LA-GlcN. The in vitro study demonstrated that LA-GlcN could selectively kill HGSOC cells without affecting normal cells; the in vivo study revealed that LA-GlcN at the dose of 50 mg kg-1 achieved a comparable tumor inhibition as doxorubicin hydrochloride (4 mg kg-1) while the overall survival of mice was extended largely due to the low toxicity, and when the dose was increased to 100 mg kg-1, the therapeutic outcomes could be improved further. This dietary hybrid which targets the excess endogenous iron to activate ferroptosis represents a promising drug for HGSOC treatment.
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Cistadenocarcinoma Seroso , Ferroptosis , Neoplasias Ováricas , Animales , Femenino , Glucosamina , Humanos , Hierro , Ácido Linoleico/uso terapéutico , Ratones , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/patologíaRESUMEN
Despite substantial observational and experimental evidence that aspirin use can provide protection against the development of colorectal neoplasia, our understanding of the molecular mechanisms involved is inadequate and limits our ability to use this drug effectively and safely for chemoprevention. We employed an untargeted plasma metabolomics approach using liquid chromatography with high-resolution mass spectroscopy to explore novel metabolites that may contribute to the chemopreventive effects of aspirin. Associations between levels of metabolic features in plasma and aspirin treatment were investigated among 523 participants in a randomized placebo-controlled clinical trial of two doses of aspirin (81 or 325 mg/day) and were linked to risk of colorectal adenoma occurrence over 3 years of follow-up. Metabolic pathways that were altered with aspirin treatment included linoleate and glycerophospholipid metabolism for the 81-mg dose and carnitine shuttle for both doses. Metabolites whose levels increased with 81 mg/day aspirin treatment and were also associated with decreased risk of adenomas during follow-up included certain forms of lysophosphatidylcholine and lysophosphatidylethanolamine as well as trihydroxyoctadecenoic acid, which is a derivative of linoleic acid and is upstream of cyclooxygenase inhibition by aspirin in the linoleate and arachidonic acid metabolism pathways. In conclusion, our findings regarding lysophospholipids and metabolites in the linoleate metabolism pathway may provide novel insights into the chemopreventive effects of aspirin in the colorectum, although they should be considered hypothesis-generating at this time. PREVENTION RELEVANCE: This research used metabolomics, an innovative discovery-based approach, to identify molecular changes in human blood that may help to explain how aspirin use reduces the risk of colorectal neoplasia in some individuals. Ultimately, this work could have important implications for optimizing aspirin use in the prevention of colorectal cancer.
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Adenoma , Anticarcinógenos , Neoplasias Colorrectales , Adenoma/tratamiento farmacológico , Antiinflamatorios no Esteroideos/uso terapéutico , Anticarcinógenos/uso terapéutico , Aspirina/farmacología , Aspirina/uso terapéutico , Neoplasias Colorrectales/epidemiología , Humanos , Ácido Linoleico/uso terapéutico , MetabolómicaRESUMEN
Purpose: To investigate the active ingredients of walnut ointment (WO) and its mechanism in repairing wounds. Methods: The ingredients of WO were detected by gas chromatographymass spectrometry. The effect of linoleic acid (LA) was tested by in vitro Alamar Blue (AB) reagent. Image J software, histological and immunohistochemical analysis were used to confirm the healing effect of LA in the porcine skin model. The animals were euthanized after the experiment by injection of pentobarbital sodium. Results: LA, 24% in WO, promotes keratinocytes and fibroblasts proliferation, which were 50.09% and 15.07% respectively higher than control (p < 0.05). The healing rate of the LA group (96.02% ± 2%, 98.58% ± 0.78%) was higher than the saline group (82.11% ± 3.37%, 88.72% ± 1.73%) at week 3 and week 4 (p < 0.05). The epidermal thickness of the LA was 0.16 ± 0.04 mm greater and the expression of the P63 and CK10 proteins was stronger in the LA group than the control (p < 0.05). Conclusions: LA, which is the main components in WO can promote full-thickness burning wounds (FBWs) by stimulating cell proliferation and differentiation.
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Pomadas/química , Cicatrización de Heridas/efectos de los fármacos , Queratinocitos/efectos de los fármacos , Ácido Linoleico/uso terapéutico , Nueces/química , Quemaduras/terapia , FibroblastosRESUMEN
Obesity is considered a serious global health issue. Patients have been predisposed to comorbidities such as dyslipidemia, cardiovascular diseases, diabetes, cancers, and osteoarthritis. Certain fats in the diet have been linked with an increase in obesity, such as saturated and trans-fats. Meanwhile, some dietary fats such as conjugated linoleic acids (CLAs) and medium-chain triglycerides (MCTs) could potentially reduce energy intake. Various mechanisms for reducing weight by CLAs and MCTs, such as increased lipolysis, improved intestinal microbiota, up-regulating peroxisome proliferator-activated receptors (PPARs), increased the expression of uncoupling protein of respiratory chain-1 (UCP-1), and affected satiety hormones are included. These bioactive compounds, CLAs and MCTs, should be used in moderate concentrations to prevent harmful effects such as insulin resistance for CLAs and hypercholesterolemia for MCTs. However, several studies have proposed CLAs or MCTs as adjuvants to the protocol used to minimize bodyweight. Our objective is to summarize the different causes of obesity and to discuss the effects of CLAs or MCTs on body weight and fat deposition in obese animals or humans.
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Dieta , Ácido Linoleico/uso terapéutico , Obesidad/dietoterapia , Triglicéridos/uso terapéutico , Animales , Peso Corporal/efectos de los fármacos , Grasas de la Dieta/metabolismo , Manejo de la Enfermedad , Humanos , Ácido Linoleico/química , Obesidad/patología , Manejo de la Obesidad , Triglicéridos/químicaRESUMEN
Obesity is a major independent risk factor for increased morbidity and mortality upon infection with Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2), which is responsible for the current coronavirus disease pandemic (COVID-19). Therefore, there is a critical need to identify underlying metabolic factors associated with obesity that could be contributing toward increased susceptibility to SARS-CoV-2 in this vulnerable population. Here, we focus on the critical role of potent endogenous lipid metabolites known as specialized pro-resolving mediators (SPMs) that are synthesized from polyunsaturated fatty acids. SPMs are generated during the transition of inflammation to resolution and have a vital role in directing damaged tissues to homeostasis; furthermore, SPMs display anti-viral activity in the context of influenza infection without being immunosuppressive. We cover evidence from rodent and human studies to show that obesity, and its co-morbidities, induce a signature of SPM deficiency across immunometabolic tissues. We further discuss how the effects of obesity upon SARS-CoV-2 infection are likely exacerbated with environmental exposures that promote chronic pulmonary inflammation and augment SPM deficits. Finally, we highlight potential approaches to overcome the loss of SPMs using dietary and pharmacological interventions. Collectively, this mini-review underscores the need for mechanistic studies on how SPM deficiencies driven by obesity and environmental exposures may exacerbate the response to SARS-CoV-2.
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Betacoronavirus , Infecciones por Coronavirus/epidemiología , Ácidos Docosahexaenoicos/deficiencia , Ácido Eicosapentaenoico/metabolismo , Ácido Linoleico/deficiencia , Lipoxinas/deficiencia , Obesidad/epidemiología , Obesidad/inmunología , Neumonía Viral/epidemiología , COVID-19 , Comorbilidad , Infecciones por Coronavirus/dietoterapia , Infecciones por Coronavirus/virología , Susceptibilidad a Enfermedades , Ácidos Docosahexaenoicos/uso terapéutico , Ácido Eicosapentaenoico/uso terapéutico , Humanos , Inflamación/metabolismo , Ácido Linoleico/uso terapéutico , Lipoxinas/uso terapéutico , Morbilidad , Obesidad/metabolismo , Pandemias , Neumonía Viral/dietoterapia , Neumonía Viral/virología , Factores de Riesgo , SARS-CoV-2RESUMEN
Active rebuilding, stabilizing, and maintaining the lipid barrier of the skin is an encouraging disease management and care concept for dry skin, atopic dermatitis (eczema, neurodermatitis), and psoriasis. For decades, corticosteroids have been the mainstay of topical therapy for atopic dermatitis; however, innovations within the scope of basic therapy are rare. In (extremely) dry, irritated, or inflammatory skin, as well as in lesions, an altered (sphingo)lipid profile is present. Recovery of a balanced (sphingo)lipid profile is a promising target for topical and personalized treatment and prophylaxis. New approaches for adults and small children are still lacking. With an ingenious combination of commonly used active ingredients, it is possible to restore and reinforce the dermal lipid barrier and maintain refractivity. Lysosomes and ceramide de novo synthesis play a key role in attenuation of the dermal lipid barrier. Linoleic acid in combination with amitriptyline in topical medication offers the possibility to relieve patients affected by dry and itchy skin, mild to moderate atopic dermatitis lesions, and eczemas without the commonly occurring serious adverse effects of topical corticosteroids or systemic antibody administration.
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Ceramidas/metabolismo , Dermatitis Atópica/metabolismo , Amitriptilina/uso terapéutico , Animales , Antioxidantes/metabolismo , Apoptosis/fisiología , Humanos , Ácido Linoleico/uso terapéutico , Esfingolípidos/metabolismoRESUMEN
The crude methanolic and hexane extracts of non-cooked, steamed and roasted from three Job's Tears cultivars were prepared and further semi-purified by liquid-liquid extraction techniques and silica gel column. The six single semi-purified extracts (F1-F6) were combined as nine cocktails (CT1, CT6, CT8, CT13, CT14, CT21, CT24, CT25 and CT31) according to the IC50 values from the preliminary study and investigated for anti-proliferative and apoptotic induction on mouth cancer cell line (KB) and immunostimulating as well as antioxidative activities. The highest anti-proliferative activity was observed in CT13 showing the IC50 value of 0.53±0.45 µg/mL which was higher than 5-fluorouracil and doxorubicin of 20.34 and 1.60 times, respectively. CT1 which was the combination of F1-F6 and CT13 which was the combination of F4-F6 exhibited significant strong synergistic activity with the combination index value (CI) of 0.28. CT1 at 200 µg/mL showed the highest percentages of apoptotic cells (40.65±10.97%) with no necrotic cells, but lower than cisplatin (100 µg/mL) of 2.18 times. CT14 gave the highest immunostimulating activity with the phagocytosis percentage of 13.0±1.7%, but lower than lipopolysaccharide of 1.08 times. CT31 gave the highest free radical scavenging and metal chelating activities with the SC50 and MC50 values of 0.73±0.07 and 1.99±0.24 µg/mL, but lower than ascorbic acid and EDTA of 18.25 and 4.33 times, respectively. The linoleic acid contents related to anti-cancer activity were also examined by HPLC. This study has demonstrated that CT1 composing of F1-F6 at the percentage ratio of 0.71:2.06:81.38: 8.47:4.92:2.46 was the potential cocktails of the semi-purified extracts from the Job's Tears which can be further developed as a novel active compound for oral cancer treatment.
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Antineoplásicos Fitogénicos , Coix/química , Ácido Linoleico/farmacología , Ácido Linoleico/uso terapéutico , Neoplasias de la Boca/tratamiento farmacológico , Neoplasias de la Boca/patología , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Semillas/química , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Humanos , Extracción Líquido-Líquido , Extractos Vegetales/aislamiento & purificaciónRESUMEN
Elevated saturated free fatty acid levels during over-nutrition lead to hypothalamic inflammation, which perturbs energy homeostasis. Whether brain-derived metabolites are coupled to the development of obesity pathogenesis during the early over-nutrition period has not been thoroughly investigated. In this study, we found increased linoleic acid, an unsaturated fatty acid, in both the whole brain and hypothalamus of mice fed a high-fat diet for 4 weeks. Furthermore, we observed that linoleic acid effectively reversed the inflammatory responses induced by palmitic acid treatment in microglial cells. Collectively, this study suggests the reversible function of linoleic acid on brain inflammation in association with microglial activation during short-term exposure to a high-fat diet.
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Antiinflamatorios/uso terapéutico , Dieta Alta en Grasa/efectos adversos , Encefalitis/tratamiento farmacológico , Ácido Linoleico/uso terapéutico , Microglía/efectos de los fármacos , Animales , Antiinflamatorios/inmunología , Encefalitis/etiología , Encefalitis/inmunología , Ácido Linoleico/inmunología , Ratones Endogámicos C57BL , Microglía/inmunología , Ácido Palmítico/efectos adversos , Ácido Palmítico/inmunologíaRESUMEN
Docetaxel (DTX) solution is among the most widely-used parenteral formulations used in advanced breast cancer therapy. However, severe side effects have been observed due to the use of ethanol and polysorbate 80. Herein, a novel DTX-based prodrug, docetaxel-linoleic acid conjugate (DTX-LA) was successfully synthesized. The high lipid solubility of DTX and DTX-LA resulted in a tendency for them to become entrapped in the oil core of the emulsions. As anticipated, nano-sized, sterically stabilized oil-in-water lipid emulsions (LMs) of DTX-LA LMs and DTX LMs were successfully constructed. Unlike DTX solution, LMs exhibited high colloidal stability and sustained-release behavior, having a narrow size distribution that was â¼220â¯nm in diameter. Compared with DTX LMs, DTX-LA LMs had a greater drug-loading capacity. Although the cytotoxicity of DTX-LA LMs was reduced in comparison with DTX solution, the pharmacokinetic study demonstrated increased bioavailability (pâ¯<â¯0.001) and half-life (pâ¯<â¯0.01). Finally, DTX-LA LMs displayed significant antitumor efficacy with reduced side effects in a 4T1 breast cancer xenograft model. Thus, the novel lipid emulsion-based docetaxel prodrug delivery system may be a promising strategy for improving intravenous administration for breast cancer treatment.
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Antineoplásicos/administración & dosificación , Neoplasias de la Mama/tratamiento farmacológico , Portadores de Fármacos/administración & dosificación , Ácido Linoleico/administración & dosificación , Taxoides/administración & dosificación , Administración Oral , Animales , Antineoplásicos/química , Antineoplásicos/farmacocinética , Antineoplásicos/uso terapéutico , Apoptosis/efectos de los fármacos , Disponibilidad Biológica , Neoplasias de la Mama/patología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Docetaxel , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/uso terapéutico , Emulsiones , Femenino , Ácido Linoleico/química , Ácido Linoleico/farmacocinética , Ácido Linoleico/uso terapéutico , Masculino , Ratones , Ratones Endogámicos BALB C , Ratas Sprague-Dawley , Taxoides/química , Taxoides/farmacocinética , Taxoides/uso terapéutico , Resultado del Tratamiento , Carga Tumoral/efectos de los fármacosRESUMEN
BACKGROUND: RT001 is a deuterated ethyl linoleate that inhibits lipid peroxidation and is hypothesized to reduce cellular damage and recover mitochondrial function in degenerative diseases such as Friedreich's ataxia. OBJECTIVE: To evaluate the safety, pharmacokinetics, and preliminary efficacy of RT001 in Friedreich's ataxia patients. DESIGN/METHODS: We conducted a phase I/II double-blind, comparator-controlled trial with 2 doses of RT001 in Friedreich's ataxia patients (9 subjects each cohort). Subjects were randomized 2:1 to receive either RT001 (1.8 or 9.0 g/day), or a matching dose of nondeuterated ethyl linoleate as comparator for 28 days. The primary endpoints were safety, tolerability, and pharmacokinetic analysis. Secondary endpoints included cardiopulmonary exercise testing and timed 25-foot walk. RESULTS: Nineteen patients enrolled in the trial, and 18 completed all safety and efficacy measurements. RT001 was found to be safe and tolerable, with plasma levels approaching saturation by 28 days. One subject with a low body mass index experienced steatorrhea taking a high dose and discontinued the study. Deuterated arachidonic acid (a brain-penetrant metabolite of RT001) was found to be present in plasma on day 28. There was an improvement in peak workload in the drug group compared to placebo (0.16 watts/kg; P = 0.008), as well as an improvement trend in peak oxygen consumption (change of 0.16 L/min; P = 0.116), and in stride speed (P = 0.15). CONCLUSIONS: RT001 was found to be safe and tolerable over 28 days, and improved peak workload. Further research into the effect of RT001 in Friedreich's ataxia is warranted. © 2018 International Parkinson and Movement Disorder Society.
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Ataxia de Friedreich/tratamiento farmacológico , Ácido Linoleico/uso terapéutico , Ácidos Linoleicos/uso terapéutico , Adolescente , Adulto , Ácido Araquidónico/metabolismo , Estudios de Cohortes , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Femenino , Ataxia de Friedreich/sangre , Humanos , Ácido Linoleico/sangre , Ácidos Linoleicos/sangre , Masculino , Persona de Mediana Edad , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenAsunto(s)
Progresión de la Enfermedad , Ataxia de Friedreich/diagnóstico , Ataxia de Friedreich/fisiopatología , Método Doble Ciego , Ataxia de Friedreich/tratamiento farmacológico , Humanos , Ácido Linoleico/uso terapéutico , Consumo de Oxígeno/efectos de los fármacos , Caminata/fisiología , Carga de TrabajoRESUMEN
BACKGROUND AND AIMS: Pruritus frequently reduces quality of life (QOL) in patients with senile xerosis. This study investigated the moisturizing and antipruritic effects of a topical emollient containing a diethylene glycol/dilinoleic acid copolymer (D/DC) in patients with pruritic senile xerosis. METHODS: This single-blind study involved 50 subjects, aged 50-75 years. Patients were randomized to self-applied treatment of the lower legs with 10% (n = 20) or 20% (n = 20) D/DC-containing cream, white petrolatum (n = 5), or no treatment (n = 5) thrice daily for four weeks. Clinical scores of skin dryness and scratch marks, skin conductance, and Skindex-16 were evaluated before and after treatment. The degree of pruritus was evaluated by visual analog scale (VAS) score once a week. RESULTS: Patients treated with 10% and 20% D/DC showed significant improvements in skin dryness and scratch mark scores, as well as increased skin conductance, compared with the untreated group, whereas white petrolatum treatment improved only skin dryness scores. Moreover, patients treated with 20% D/DC showed significant improvements in skin dryness scores and skin conductance compared with white petrolatum treatment. The VAS scores in the D/DC-treated and white petrolatum-treated groups were significantly lower than in the untreated group, being particularly lower after one week of treatment with 20% D/DC. CONCLUSION: Topical application of an emollient containing D/DC is effective in improving skin dryness and pruritus in patients with senile xerosis.
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Emolientes/uso terapéutico , Glicoles de Etileno/uso terapéutico , Dermatosis de la Pierna/tratamiento farmacológico , Ácido Linoleico/uso terapéutico , Prurito/tratamiento farmacológico , Envejecimiento de la Piel , Enfermedades de la Piel/tratamiento farmacológico , Anciano , Femenino , Respuesta Galvánica de la Piel/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , Vaselina/uso terapéutico , Método Simple Ciego , Escala Visual AnalógicaRESUMEN
BACKGROUND: Previous studies indicated that tomato is a rich source of phytochemicals that act on different tumours. In this research, the phytochemical composition of selected tomato varieties was assessed by GLC and UHPLC/HPLC-MS, as well as their anti-tumour activities on HT-29 colorectal cancer cells. RESULTS: Significant differences were found among tomato varieties; lycopene was high in Racimo, phenolics in Pera, sterols in Cherry, and linoleic acid predominated in all varieties. The MTT and LDH assays showed significant time- and concentration-dependent inhibitory/cytotoxic effects of all tomato varieties on HT-29 cells. Furthermore, the joint addition of tomato carotenoids and olive oil to HT-29 cell cultures induced inhibitory effects significantly higher than those obtained from each of them acting separately, while no actions were exercised in CCD-18 normal cells. CONCLUSION: Tomato fruits constitute a healthy source of phytochemicals, although differences exist among varieties. In vitro, all of them inhibit colorectal cancer cell proliferation with Racimo variety at the top, and exercising a selective action on cancer cells by considering the lack of effects on CCD-18 cells. Furthermore, synergy was observed between olive oil and tomato carotenoids in inhibiting HT-29 cancer cell proliferation; conversely, phenolics showed no significant effects and hindered carotenoids actions. © 2016 Society of Chemical Industry.
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Antineoplásicos Fitogénicos/uso terapéutico , Carotenoides/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Grasas Insaturadas en la Dieta/uso terapéutico , Frutas/química , Fenoles/uso terapéutico , Solanum lycopersicum/química , Antineoplásicos Fitogénicos/farmacología , Antioxidantes/análisis , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Carotenoides/análisis , Carotenoides/farmacología , Proliferación Celular , Neoplasias Colorrectales/dietoterapia , Grasas Insaturadas en la Dieta/análisis , Grasas Insaturadas en la Dieta/farmacología , Sinergismo Farmacológico , Células HT29 , Humanos , Ácido Linoleico/análisis , Ácido Linoleico/farmacología , Ácido Linoleico/uso terapéutico , Licopeno , Solanum lycopersicum/clasificación , Aceite de Oliva/farmacología , Aceite de Oliva/uso terapéutico , Fenoles/análisis , Fenoles/farmacología , Fitoquímicos/análisis , Fitoquímicos/farmacología , Fitoquímicos/uso terapéutico , Fitosteroles/análisis , Fitosteroles/farmacología , Fitosteroles/uso terapéutico , Fitoterapia , Extractos Vegetales/química , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Especificidad de la EspecieRESUMEN
Pancreatic enzyme therapy does not normalize dietary fat absorption in patients with cystic fibrosis and pancreatic insufficiency. Efficacy of LYM-X-SORB (LXS), an easily absorbable lipid matrix that enhances fat absorption, was evaluated in a 12-month randomized, double-blinded, placebo-controlled trial with plasma fatty acids (FA) and coefficient of fat absorption (CFA) outcomes. A total of 110 subjects (age 10.4â±â3.0 years) were randomized. Total FA increased with LXS at 3 and 12 months (+1.58, +1.14 mmol/L) and not with placebo (Pâ=â0.046). With LXS, linoleic acid (LA) increased at 3 and 12 months (+298, +175 nmol/mL, Pâ≤â0.046), with a 6% increase in CFA (Pâ<â0.01). LA increase was significant in LXS versus placebo (445 vs 42 nmol/mL, Pâ=â0.038). Increased FA and LA predicted increased body mass index Z scores. In summary, the LXS treatment improved dietary fat absorption compared with placebo as indicated by plasma FA and LA and was associated with better growth status.
Asunto(s)
Fibrosis Quística/tratamiento farmacológico , Grasas de la Dieta/metabolismo , Insuficiencia Pancreática Exocrina/tratamiento farmacológico , Lípidos/uso terapéutico , Adolescente , Niño , Fenómenos Fisiológicos Nutricionales Infantiles , Fibrosis Quística/complicaciones , Fibrosis Quística/enzimología , Fibrosis Quística/metabolismo , Insuficiencia Pancreática Exocrina/complicaciones , Insuficiencia Pancreática Exocrina/enzimología , Femenino , Humanos , Absorción Intestinal , Ácido Linoleico/uso terapéutico , Masculino , Resultado del TratamientoRESUMEN
Background - Idiopathic pulmonary fibrosis (IPF) is a chronic disease characterized by histopathological lesions in lung tissue. This is the most common and most severe idiopathic interstitial pneumonias. Current treatments are based on the combination of corticosteroids and immunosuppressants, but their effectiveness is still debated. Purpose of work - Testing the preventive effect of Pistacia Lentiscus oil, known for its antioxidant, anti-mutagenic and anti-proliferative effects, on a model of experimental lung fibrosis. Methods - Two groups of rats received an intratracheal injection of bleomycin (4.5 mg / kg). The first group, control (n = 20 rats), has received no treatment. The second group was treated with Pistacia Lentiscus oil (n = 20 rats) for 30 days before fibrosis induction, by daily gavage oil Pistacia Lentiscus oil (3,33ml / kg). This treatment was continued for 10 days. At the end of the experimental period, all rats were sacrificed and the lung tissue was examined histopathologically and immunostained for TGFß. Results - The chromatographic profile oil Pistacia Lentiscus oil shows the dominance of two fatty acids that are linoleic acid and palmitic acid representing respectively 70.57 and 24.67%. Our results also show a decrease in the distribution of TGFß both at the level of the inflammatory infiltrate and at the level of the pulmonary parenchyma histiocytes of rats treated with Pistacia Lentiscus oil compared with control rats. However, these changes are not accompanied by statistically significant changes of fibrosis score and inflammatory index. Conclusion - Our results are interesting to consider. Further studies using higher doses of Pistacia Lentiscus oil are important to conduct.