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1.
Ann Hematol ; 103(5): 1493-1511, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-37951852

RESUMEN

Recent advancements have focused on enhancing factor VIII half-life and refining its delivery methods, despite the well-established knowledge that factor VIII deficiency is the main clotting protein lacking in hemophilia. Consequently, both viral and non-viral delivery systems play a crucial role in enhancing the quality of life for hemophilia patients. The utilization of viral vectors and the manipulation of non-viral vectors through targeted delivery are significant advancements in the field of cellular and molecular therapies for hemophilia. These developments contribute to the progression of treatment strategies and hold great promise for improving the overall well-being of individuals with hemophilia. This review study comprehensively explores the application of viral and non-viral vectors in cellular (specifically T cell) and molecular therapy approaches, such as RNA, monoclonal antibody (mAb), and CRISPR therapeutics, with the aim of addressing the challenges in hemophilia treatment. By examining these innovative strategies, the study aims to shed light on potential solutions to enhance the efficacy and outcomes of hemophilia therapy.


Asunto(s)
Hemofilia A , Humanos , Hemofilia A/terapia , Hemofilia A/genética , Calidad de Vida , Terapia Genética/métodos , Factor VIII , Factores de Coagulación Sanguínea , Vectores Genéticos
2.
J Nat Prod ; 87(1): 58-67, 2024 01 26.
Artículo en Inglés | MEDLINE | ID: mdl-38159296

RESUMEN

Phytochemical investigation of the MeOH extract of Pinus eldarica needles led to the isolation and identification of a new clerodane-type diterpene, pinuseldarone (1), along with a known flavonoid, 5,4'-dihydroxy-3,7,8-trimethoxy-6-C-methylflavone (2), through HPLC purification. The structure of the new compound 1 was elucidated using spectroscopic methods, including 1D and 2D NMR, as well as HRESIMS. Its absolute configuration was established through NOESY analysis and computational methods, including electronic circular dichroism (ECD) calculations and gauge-including atomic orbital NMR chemical shift calculations, followed by DP4+ probability analysis. The metabolic implications of the isolated compounds were assessed using a cultured brown adipocyte model derived from murine brown adipose tissue. It was observed that treatment with dihydroxy-3,7,8-trimethoxy-6-C-methylflavone (2) downregulates the adipogenic marker C/EBPδ and fatty acid transporter CD36, resulting in a significant reduction in lipid accumulation during brown adipocyte differentiation. However, pinuseldarone (1) treatment did not affect brown adipocyte differentiation. Interestingly, pretreatment with pinuseldarone (1) potentiated the pharmacological stimulation of brown adipocytes, seemingly achieved by sensitizing their response to ß3-adrenoreceptor signaling. Therefore, our findings indicate that phytochemicals derived from P. eldarica needles could potentially serve as valuable compounds for adjusting the metabolic activity of brown adipose tissue, a vital component in maintaining whole-body metabolic homeostasis.


Asunto(s)
Diterpenos de Tipo Clerodano , Pinus , Animales , Ratones , Adipogénesis , Adipocitos Marrones/metabolismo , Termogénesis
3.
Compr Rev Food Sci Food Saf ; 23(3): e13370, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38783570

RESUMEN

Glycomacropeptide (GMP) is a bioactive peptide derived from whey protein, consisting of 64 amino acids. It is a phenylalanine-free peptide, making it a beneficial dietary option for individuals dealing with phenylketonuria (PKU). PKU is an inherited metabolic disorder characterized by high levels of phenylalanine in the bloodstream, resulting from a deficiency of phenylalanine dehydrogenase in affected individuals. Consequently, patients with PKU require lifelong adherence to a low-phenylalanine diet, wherein a significant portion of their protein intake is typically sourced from a phenylalanine-free amino acid formula. GMP has several nutritional values, numerous bioactivity properties, and therapeutic effects in various inflammatory disorders. Despite all these features, the purification of GMP is an imperative requirement; however, there are no unique methods for achieving this goal. Traditionally, several methods have been used for GMP purification, such as thermal or acid treatment, alcoholic precipitation, ultrafiltration (UF), gel filtration, and membrane separation techniques. However, these methods have poor specificity, and the presence of large amounts of impurities can interfere with the analysis of GMP. More efficient and highly specific GMP purification methods need to be developed. In this review, we have highlighted and summarized the current research progress on the major biological features and purification methodologies associated with GMP, as well as providing an extensive overview of the recent developments in using charged UF membranes for GMP purification and the influential factors.


Asunto(s)
Caseínas , Caseínas/química , Fragmentos de Péptidos/análisis , Fragmentos de Péptidos/química , Humanos , Fenilcetonurias
4.
Pharm Dev Technol ; 29(4): 353-358, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38528824

RESUMEN

One of the widely used approaches for improving the dissolution of poorly water-soluble drugs is particle size reduction. Ball milling is a mechanical, top-down technique used to reduce particle size. The effect of ball number, ball size, and milling speed on the properties of milled Aprepitant is evaluated. A full factorial design was employed to investigate the influence of affecting factors on particle size reduction. The initial suspension was made by suspending the drug in distilled water using excipients followed by milling in a planetary ball mill. Ball size, ball number, and milling speed modulated particle size distribution of Aprepitant. Increasing the number of balls from minimum to maximum for each ball size led to approximately a 28% reduction in mean particle size, a 37% decrease in D90%, and a 25% decrease in the ratio of volume mean particle diameter to numeric mean particle diameter. On average, using 10 mm balls instead of 30 mm balls reduced mean particle size by 1.689 µm. As a result, ball size, ball number, and milling speed are three effective factors in the process of ball milling. By increasing the ball number and decreasing the ball size, efficient micronization of drug particles takes place and the particle size is more uniform.


Asunto(s)
Aprepitant , Composición de Medicamentos , Excipientes , Tamaño de la Partícula , Aprepitant/química , Aprepitant/administración & dosificación , Composición de Medicamentos/métodos , Excipientes/química , Solubilidad , Química Farmacéutica/métodos
5.
Exp Dermatol ; 32(9): 1459-1467, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37283479

RESUMEN

Opioid and local anaesthetic receptors are abundantly concentrated in different layers of the skin. Therefore, simultaneous targeting of these receptors can produce more potent dermal anaesthesia. Herein, we developed lipid-based nanovesicles for the co-delivery of buprenorphine and bupivacaine to efficiently target skin-concentrated pain receptors. Invasomes incorporating two drugs were prepared by ethanol injection method. Subsequently, the size, zeta potential, encapsulation efficiency, morphology, and in-vitro drug release of vesicles were characterized. Ex-vivo penetration features of vesicles were then investigated by the franz diffusion cell on the full-thickness human skin. Wherein, it was demonstrated that invasomes penetrated the skin deeper and delivered bupivacaine more effectively than buprenorphine to the target site. The superiority of invasome penetration was further evidenced by the results of ex-vivo fluorescent dye tracking. Estimation of in-vivo pain responses by the tail-flick test revealed that compared with the liposomal group, the group receiving invasomal formulation and drug-free invasomal formulation (only containing menthol) displayed increased analgesia in the initial times of 5 and 10 min. Also, no signs of oedema or erythema were observed in the Daze test in any of the rats receiving the invasome formulation. Finally, ex-vivo and in-vivo assays demonstrated efficiency in delivering both drugs into deeper layers of skin and exposing them to the located pain receptors, which improves the time of onset and the analgesic effects. Hence, this formulation appears to be a promising candidate for tremendous development in the clinical setting.


Asunto(s)
Analgesia , Buprenorfina , Humanos , Ratas , Animales , Bupivacaína/farmacología , Buprenorfina/farmacología , Piel , Liposomas/farmacología , Dolor
6.
Crit Rev Food Sci Nutr ; 63(19): 4009-4025, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-34751073

RESUMEN

As a bioactive component in Capsicum species, capsaicin is a compound of hot chili peppers which is known as the main substance responsible for the spiciness of these fruits. Besides its taste and physiological effects, it exhibits good antioxidant activity in food matrix and antimicrobial activity against foodborne pathogens and viruses. Considering its low stability and bioaccessibility, and also regarding its irritation, the entrapment methods of capsaicin are fully developed. To compensate the limitations of capsaicin, various encapsulation methods have been used so far, including coacervation, emulsion, spray chilling, and liposomal delivery. Capsaicin has been widely used as a flavoring and preservative agent in food formulations and even as an active compound in packaging film and functional foods. This review provides an overview of the techno-functional properties, stabilization procedures, and burgeoning usages of capsaicin in the latest studies of the food sector. So, it may introduce new windows for the application of this compound.


Asunto(s)
Capsaicina , Capsicum , Capsaicina/farmacología , Frutas/química , Industria de Alimentos , Antioxidantes/farmacología
7.
Support Care Cancer ; 32(1): 42, 2023 Dec 19.
Artículo en Inglés | MEDLINE | ID: mdl-38110726

RESUMEN

PURPOSE: Neutropenic fever remains a major complication in acute leukemia. Decolonization is assumed as a promising intervention for eradicating causative agents of infection. METHODS: In this randomized clinical trial, 96 patients with acute leukemia were assigned randomly to mupirocin nasal drop 2% (n = 32), chlorhexidine mouthwash 0.2% (n = 33), and control group (n = 31). In control group, patients did not receive any medication for decolonization. All patients received treatment for 5 days (2 days prior to chemotherapy until 3 days after chemotherapy). Pharynx and nasal swabs were taken prior to the intervention and at the end of decolonization period in all groups. Antibiotic susceptibility testing was performed by the disc diffusion method in order to identify bacterial isolates. RESULTS: Bacterial recovery of both nasal and pharynx swabs was observed after global decolonization with mupirocin nasal drop. Decolonization with mupirocin significantly eradicated Coagulase-negative staphylococci (CONS) in both nasal and pharynx swabs (p-value = 0.000). Moreover, mupirocin decreased Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (MRSA) species. Chlorhexidine mouthwash significantly eradicated CONS in pharynx swabs (p-value = 0.000). In addition, both decolonization strategies decreased both antibiotic use and frequency of fever in leukemic patients. CONCLUSION: Global decolonization with mupirocin nasal drop not only eradicates both nasal and pharynx microorganisms, but also reduces antibiotic requirement and frequency of fever in patients with acute leukemia. The protocol of the present study was approved on December 2016 (registry number: IRCT20160310026998N6).


Asunto(s)
Leucemia Mieloide Aguda , Staphylococcus aureus Resistente a Meticilina , Infecciones Estafilocócicas , Humanos , Mupirocina/uso terapéutico , Clorhexidina/uso terapéutico , Antisépticos Bucales/uso terapéutico , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/microbiología , Antibacterianos/uso terapéutico , Leucemia Mieloide Aguda/tratamiento farmacológico
8.
J Pharm Pharm Sci ; 26: 11466, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37206631

RESUMEN

Purpose: An efficient, cost-effective and non-invasive test is required to overcome the challenges faced in the process of bioequivalence (BE) studies of various orally inhaled drug formulations. Two different types of pressurized meter dose inhalers (MDI-1 and MDI-2) were used in this study to test the practical applicability of a previously proposed hypothesis on the BE of inhaled salbutamol formulations. Methods: Salbutamol concentration profiles of the exhaled breath condensate (EBC) samples collected from volunteers receiving two inhaled formulations were compared employing BE criteria. In addition, the aerodynamic particle size distribution of the inhalers was determined by employing next generation impactor. Salbutamol concentrations in the samples were determined using liquid and gas chromatographic methods. Results: The MDI-1 inhaler induced slightly higher EBC concentrations of salbutamol when compared with MDI-2. The geometric MDI-2/MDI-1 mean ratios (confidence intervals) were 0.937 (0.721-1.22) for maximum concentration and 0.841 (0.592-1.20) for area under the EBC-time profile, indicating a lack of BE between the two formulations. In agreement with the in vivo data, the in vitro data indicated that the fine particle dose (FPD) of MDI-1 was slightly higher than that for the MDI-2 formulation. However, the FPD differences between the two formulations were not statistically significant. Conclusion: EBC data of the present work may be considered as a reliable source for assessment of the BE studies of orally inhaled drug formulations. However, more detailed investigations employing larger sample sizes and more formulations are required to provide more evidence for the proposed method of BE assay.


Asunto(s)
Albuterol , Nebulizadores y Vaporizadores , Humanos , Proyectos Piloto , Equivalencia Terapéutica , Administración por Inhalación
9.
J Sep Sci ; 46(21): e2300323, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37691072

RESUMEN

This study introduces a reliable and inexpensive magnetic dispersive solid phase extraction to extract imipramine and its primary metabolite (desipramine) from urine samples. To accomplish this aim, Fe3 O4 magnetic nanoparticles were synthesized by sonication, subsequently, polycarbonate was precipitated gradually onto the surface of them to form the adsorbent. Extraction recoveries of 85% and 76%, enrichment factors of 57 and 51, limits of detection of 2.5 and 2.8 µg/L, and limits of quantification of 8.3 and 9.3 µg/L were obtained for imipramine and desipramine under the optimal conditions, respectively. In addition, relative standard deviations for intra- (n = 6) and inter-day (n = 5) precisions at two concentrations (50 and 100 µg/L of each analyte) were less than or equal to 4%. Short extraction time, good repeatability, high enrichment factors, and simplicity are the main advantages of the proposed method.


Asunto(s)
Imipramina , Nanopartículas de Magnetita , Desipramina , Extracción en Fase Sólida , Cromatografía Líquida de Alta Presión , Fenómenos Magnéticos
10.
J Mater Sci Mater Med ; 34(10): 47, 2023 Sep 21.
Artículo en Inglés | MEDLINE | ID: mdl-37735291

RESUMEN

Numerous infections are linked to Pseudomonas aeruginosa. It is one of the major medical concerns because of virulence and antibiotic resistance. Antibiotic encapsulation in liposomes is a good strategy for controlling infections caused by this microorganism. Evaluation of anti-Pseudomonas aeruginosa effect of liposomal form of Imipenem/Cilastatin in vitro condition. By using the disk agar diffusion technique, the isolates' pattern of antibiotic resistance was identified. The antibiotic was placed into the nanoliposome after it had been made using the thin layer and ethanol injection techniques. SEM and DLS were used to determine the size, shape, and zeta potential of the encapsulated drug form and the empty nanoliposome. Additionally, Imipenem/Cilastatin encapsulation in nanoliposomes was studied using FT-IR spectroscopy. In the microbial assay experiments the MIC, MBC and MBEC of liposomal and free drug forms were determined. The nanoparticles were spherical, with a diameter ranging from 30 to 39 nm, and the EE% in the thin layer and ethanol injection procedures were 97 and 98, respectively. Imipenem/Cilastatin nanoliposomes showed peaks at 3009 cm-1 and 1650 cm-1, demonstrating the thermodynamic stability for the chemical structure of the drug enclosed and validating the encapsulation of antibiotic in the nanoliposomes. When compared to free drug forms, nanoliposomes had lower MIC and MBC values in the majority of the isolates and had a greater ability to eradicate the biofilm formation. It was shown that the two nanoliposome preparation techniques were more efficient in 80% of the isolates, which had outcomes that were consistent with those of numerous other investigations. Overall, we demonstrated that the antibacterial activity of nanoliposomes was higher than that of the free drug form based on the evaluation of their MIC and MBC. Pharmaceutical nanoliposome techniques provide an excellent future perspective on how to manage microbial infections that are resistant to antibiotics.


Asunto(s)
Antibacterianos , Pseudomonas aeruginosa , Espectroscopía Infrarroja por Transformada de Fourier , Combinación Cilastatina e Imipenem , Antibacterianos/farmacología , Etanol , Liposomas , Biopelículas
11.
Mikrochim Acta ; 190(7): 253, 2023 06 07.
Artículo en Inglés | MEDLINE | ID: mdl-37286753

RESUMEN

An innovative aptamer labeled with 5-FAM has been developed with a high affinity for Yersinia enterocolitica (Y. enterocolitica) using graphene oxide (GO) as a quenching platform. The selectivity of the prepared system was evaluated in the presence of common coexisted bacteria like Yersinia pseudotuberculosis, Staphylococcus aureus, Listeria monocytogenes, Escherichia coli, and Salmonella typhimurium. Some experimental factors like pH and stability were investigated. The results showed that in the absence of Y. enterocolitica, aptamer labeled with 5-FAM was bonded with GO, causing fluorescence to be relatively weak. After the addition of Y. enterocolitica, the aptamer is released from the GO surface and binds to the target bacteria, and significantly increases the fluorescence intensity with an excitation wavelength of 410 nm and an emission wavelength of 530 nm. After optimizing all conditions, the system exhibited a wide linear response for Y. enterocolitica in the concentration range 10 to 1.0 × 109 CFU•mL-1 and the limit of detection (LOD) was 3 CFU•mL-1. This system demonstrated that GO-designed aptamers can be successful in detecting Y. enterocolitica in whole-cell forms, making them potentially useful for screening and rapid detection.


Asunto(s)
Yersinia enterocolitica , Yersinia pseudotuberculosis , Límite de Detección , Salmonella typhimurium , Oligonucleótidos , Escherichia coli
12.
Reprod Med Biol ; 22(1): e12509, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36949822

RESUMEN

Purpose: The authors developed nanostructured lipid carriers (NLCs) loaded with sirolimus (SRL) and cyclosporine (CsA) to improve their therapeutic efficacy in recurrent pregnancy loss (RPL) patients. Methods: Mono-delivery and co-delivery of SRL and CsA by NLCs (S-NLCs, C-NLCs, and S-C-NLCs) were developed. The MTT assay was used to study the optimum dose of formulations. PCR, Western blotting, and ELISA were also conducted. Results: Well-designed nanodrugs with a suitable size, zeta potential, desirable encapsulation efficiency drug loading, and cellular uptake confirmed optimum formulations. Based on cell viability, the amounts of SRL and CsA could be reduced greatly due to the co-delivery by NLCs. Following S-NLCs and C-NLCs interventions in T cells of patients with RPL and immune abnormality, a significant difference was observed in transcription factors and cytokine levels of Th1, Th17, and Tregs compared with healthy samples. Thus, a higher level of pro-inflammatory cytokines (IFN-γ, TNF-α, IL-17, and IL-21) and their regulators (T-bet and RORγt), as well as a lower level of an anti-inflammatory cytokine (IL-10) and its regulatory (Foxp3), were observed. However, no significant difference was found following the S-C-NLCs intervention. Conclusions: S-C-NLCs effectively balance the immune responses in peripheral T cells in RPL patients to induce maternal immune tolerance.

13.
Toxicol Appl Pharmacol ; 446: 116036, 2022 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-35487267

RESUMEN

The novel folate conjugated Thermo/pH-responsive magnetic nanoparticles (folate-poly-MNPs) have been developed as a potential nanocarrier for improving site-specific drug delivery, tumor drug accumulation, and therapeutic effects while reducing the adverse effects of conventional drug delivery systems. To evaluate the anticancer efficacy of developed tumor-targeted drug delivery system, forty rat models of breast cancer received saline as control, DOX, DOX-poly-MNPs, and DOX-folate-poly-MNPs at a dose of 2 mg/kg/48 h. The DOX-folate-poly-MNPs showed a significant increase in protein expression of BAX and C-caspase-3 with concomitant downregulation of Bcl-2 expression and ki67 proliferation index compared to the DOX group. The synergistic antitumor efficacy of passive and active drug targeting led to enhanced drug uptake, increased tumor cell apoptosis, decreased tumor volume, and a prolonged survival rate in animals, suggesting that DOX-folate-poly-MNPs may prove to be a promising nanomedicine for the smart treatment of breast cancer in the future.


Asunto(s)
Nanopartículas de Magnetita , Nanopartículas , Neoplasias , Animales , Línea Celular Tumoral , Doxorrubicina/farmacología , Portadores de Fármacos , Sistemas de Liberación de Medicamentos , Ácido Fólico , Concentración de Iones de Hidrógeno , Ratas
14.
Crit Rev Food Sci Nutr ; : 1-17, 2022 Oct 12.
Artículo en Inglés | MEDLINE | ID: mdl-36222353

RESUMEN

Phenolic acids (PA) are types of phytochemicals with health benefits. The interaction between proteins and PAs can cause minor or extensive changes in the structure of proteins and subsequently affect various protein properties. This study investigates the protein/PA (PPA) interaction and its effects on the structural, physicochemical, and functional properties of the system. This work particularly focused on the ability of PAs as a subgroup of phenolic compounds (PC) on the modification of proteins. Different aspects including the influence of structure affinity relationship and molecular weight of PA on the protein interaction have been discussed in this review. The physicochemical properties of PPA change mainly due to the change of hydrophilic/hydrophobic parts and/or the formation of some covalent and non-covalent interactions. Furthermore, PPA interactions affecting functional properties were discussed in separate sections. Due to insufficient studies on the interaction of PPAs, understanding the mechanism and also the type of binding between protein and PA can help to develop a new generation of PPA. These systems seem to have good capabilities in the formulation of low-fat foods like high internal Phase Emulsions, drug delivery systems, hydrogel structures, multifunctional fibers or packaging films, and 3 D printing in the meat processing industry.

15.
J Nanobiotechnology ; 20(1): 290, 2022 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-35717383

RESUMEN

BACKGROUND: Pain is a vital sense that indicates the risk of injury at a particular body part. Successful control of pain is the principal aspect in medical treatment. In recent years, the advances of nanotechnology in pain management have been remarkable. In this review, we focus on literature and published data that reveal various applications of nanotechnology in acute and chronic pain management. METHODS: The presented content is based on information collected through pain management publications (227 articles up to April 2021) provided by Web of Science, PubMed, Scopus and Google Scholar services. RESULTS: A comprehensive study of the articles revealed that nanotechnology-based drug delivery has provided acceptable results in pain control, limiting the side effects and increasing the efficacy of analgesic drugs. Besides the ability of nanotechnology to deliver drugs, sophisticated nanosystems have been designed to enhance imaging and diagnostics, which help in rapid diagnosis of diseases and have a significant impact on controlling pain. Furthermore, with the development of various tools, nanotechnology can accurately measure pain and use these measurements to display the efficiency of different interventions. CONCLUSIONS: Nanotechnology has started a new era in the pain management and many promising results have been achieved in this regard. Nevertheless, there is still no substantial and adequate act of nanotechnology in this field. Therefore, efforts should be directed to broad investigations.


Asunto(s)
Nanopartículas , Manejo del Dolor , Sistemas de Liberación de Medicamentos/métodos , Humanos , Nanomedicina/métodos , Nanopartículas/uso terapéutico , Nanotecnología/métodos , Dolor/tratamiento farmacológico
16.
Cancer Cell Int ; 21(1): 100, 2021 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-33568147

RESUMEN

BACKGROUND: The expansion and metastasis of colorectal cancers are closely associated with the dynamic growth of cancer stem cells (CSCs). This study aimed to explore the possible effect of LXR (a regulator of glycolysis and lipid hemostasis) in the tumorgenicity of human colorectal CD133 cells. METHODS: Human HT-29 CD133+ cells were enriched by MACS and incubated with LXR agonist (T0901317) and antagonist (SR9243) for 72 h. Cell survival was evaluated using MTT assay and flow cytometric analysis of Annexin-V. The proliferation rate was measured by monitoring Ki-67 positive cells using IF imaging. The modulation of LXR was studied by monitoring the activity of all factors related to ABC transporters using real-time PCR assay and western blotting. Protein levels of metabolic enzymes such as PFKFB3, GSK3ß, FASN, and SCD were also investigated upon treatment of CSCs with LXR modulators. The migration of CSCs was monitored after being exposed to LXR agonist using scratch and Transwell insert assays. The efflux capacity was measured using hypo-osmotic conditions. The intracellular content of reactive oxygen species was studied by DCFH-DA staining. RESULTS: Data showed incubation of CSCs with T0901317 and SR9243 reduced the viability of CD133 cells in a dose-dependent manner compared to the control group. The activation of LXR up-regulated the expression and protein levels of ABC transporters (ABCA1, ABCG5, and ABCG8) compared to the non-treated cells (p < 0.05). Despite these effects, LXR activation suppressed the proliferation, clonogenicity, and migration of CD133 cells, and increased hypo-osmotic fragility (p < 0.05). We also showed that SR9243 inhibited the proliferation and clonogenicity of CD133 cells through down-regulating metabolic enzymes PFKFB3, GSK3ß, FASN, and SCD as compared with the control cells (p < 0.05). Intracellular ROS levels were increased after the inhibition of LXR by SR9243 (p < 0.05). Calling attention, both T0901317 and SR9243 compounds induced apoptotic changes in cancer stem cells (p < 0.05). CONCLUSIONS: The regulation of LXR activity can be considered as a selective targeting of survival, metabolism, and migration in CSCs to control the tumorigenesis and metastasis in patients with advanced colorectal cancers.

17.
Ecotoxicology ; 30(2): 361-372, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33566273

RESUMEN

Nanotechnology is a new field in the pesticide industry. Nanopesticides represent an emerging technological tool that offers a range of benefits including increased efficacy, durability, and reduction in the amounts of used active ingredients. However, due to the lack of studies on the toxicity and the sublethal effects on pests and natural enemies, the extent of action and fate of these nanopesticdes is still not fully understood limitting thus their wide use. In this study, we encapsulated the pirimicarb insecticide using nanostructured lipid carriers (NLC) and investigated the toxicity and sublethal effects (LC25) of the resulting nanocapsules against the cabbage aphid, Brevicoryne brassicae (Linnaeus) (Hemiptera: Aphididae) and its natural enemy the green lacewings Chrysoperla carnea (Stephens) (Neuroptera: Chrysopidae). Nanoencapsulation of pirimicarb enhanced 12.6-fold its toxicity to cabbage aphids compared to its commercial formulation. Furthermore, analysis of the age-stage, two-sex life table showed that negative effects on the B. brassicae aphid population growth were observed on F0 and F1 generations when aphids of parental (F0) generation were exposed to subelethal dose (LC25) of both formulations of pirimicarb. However, negative effects from sublethal exposure to the commercial and nanoformulated pirimicarb resulted in significant reduction on the net reproductive rate, intrinsic rate of natural increase, and finite rate of increase of the green lacewings C. carnea. Our findings indicate that the approaches and assumptions used to assess the risks of conventional insecticides may not apply for nanopesticides. Further research is still needed to better understand the environmental impact of these compounds.


Asunto(s)
Áfidos , Insecticidas , Animales , Carbamatos , Insectos , Insecticidas/toxicidad , Pirimidinas
18.
Drug Dev Ind Pharm ; 47(11): 1733-1743, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-35156468

RESUMEN

BACKGROUND: Antioxidants that used for the infertility treatment cannot have their complete effectiveness, because of their instability in the culture medium. SIGNIFICANCE: One of the most advances, in the drug delivery systems, is nanoliposomes-loaded, as biodegradable and bioavailable carriers. Hormonal and antioxidant agents encapsulating inside the nanoliposomes were used, to increase the effectiveness of antioxidants in the sperm culture medium. MATERIALS: Semen sample from 15 asthenospermia were divided into 10 equal parts. After preparation, the sperms were incubated with free form of drugs and nanocarriers contained resveratrol, catalase, resveratrol-catalase and testosterone for 45 min. All sperm parameters, sperm DNA and gene expressions were evaluated before and after freezing. RESULTS: Before freezing, all nanocarriers and free testosterone showed higher sperm motility compared to free drugs (p=.000). Free Testosterone and free resveratrol-catalase had higher DNA damage compared to nanocarriers (p=.000). Before freezing, the blank nanoliposome and testosterone nanoliposomes had the lowest HSP70 gene expression respectively (p = 0.005) (p = 0.001). After freezing, a significant reduction in sperm motility was observed in the free resveratrol-catalase group (p=.003). Also, a significant increase in sperm viability was observed in the free testosterone and nanoliposomes of blank and testosterone (p > 0.05). The least DNA fragmentation was related to catalase nanoliposomes (p=.000). All nanoliposomes, especially catalase, had the highest percentage of class I morphology compared to the control group (p=.000). CONCLUSIONS: Nanoliposomes could improve the sperm parameters and DNA integrity before and after freezing, by increasing the effectiveness of antioxidants. So, it can be recommended in the ART lab.


Asunto(s)
Antioxidantes , Preservación de Semen , Testosterona , Antioxidantes/farmacología , Astenozoospermia , Catalasa/farmacología , Criopreservación , ADN , Expresión Génica , Humanos , Liposomas , Masculino , Nanopartículas , Resveratrol/farmacología , Motilidad Espermática , Espermatozoides , Testosterona/farmacología
19.
Int J Mol Sci ; 22(12)2021 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-34205739

RESUMEN

The incidence of various types of cancer is increasing globally. To reduce the critical side effects of cancer chemotherapy, naturally derived compounds have been considered for cancer treatment. Gymnosperms are a group of plants found worldwide that have traditionally been used for therapeutic applications. Paclitaxel is a commercially available anticancer drug derived from gymnosperms. Other natural compounds with anticancer activities, such as pinostrobin and pinocembrin, are extracted from pine heartwood, and pycnogenol and enzogenol from pine bark. Gymnosperms have great potential for further study for the discovery of new anticancer compounds. This review aims to provide a rational understanding and the latest developments in potential anticancer compounds derived from gymnosperms.


Asunto(s)
Antineoplásicos Fitogénicos , Cycadopsida/química , Neoplasias/tratamiento farmacológico , Humanos
20.
J Food Sci Technol ; 57(6): 2198-2205, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32431346

RESUMEN

The fortification of the processed cheese (PC) with bioactive compounds can increase their benefits for the health and also consumer acceptance. In the present study, rheological, chemical and sensory characteristics of the processed cheese containing different quantities of tomato powder (0%, 1%, 2% and 4% wt/wt) with the appropriate levels of bioactive components were evaluated during 90 days of storage. The results showed that the PC samples containing tomato powder (PCTs) had higher levels of proteolysis extent, phenolic and lycopene contents and antioxidant activity. However, the PCTs had lower levels of pH and lipolysis indexes. Generally, lycopene and phenolic contents and antioxidant activity decreased and pH, proteolysis and lipolysis index increased during storage. The results obtained from the frequency sweep test and temperature sweep test, indicated that, the samples had solid-type structure and tomato powder decreased the solid like behavior of the PC (G' > G″). Sensory analysis showed that the processed cheese with the average level of tomato powder (2%) had maximum scores of flavor, color and total acceptance and also the PCTs were significantly (P < 0.05) less rigid and more spreadable than the control PC and these findings were according to the achievements obtained by dynamic oscillation rheometry. Finally overall results indicated that tomato powder could be helpful for the manufacturing of new product with different functional and sensory specifications.

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