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1.
Small ; : e2400673, 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38700057

RESUMEN

Parasitic side reactions and dendrites formation hinder the application of aqueous zinc ion batteries due to inferior cycling life and low reversibility. Against this background, N-methyl formamide (NMF), a multi-function electrolyte additive is applied to enhance the electrochemical performance. Studied via advanced synchrotron radiation spectroscopy and DFT calculations, the NMF additive simultaneously modifies the Zn2+ solvation structure and ensures uniform zinc deposition, thus suppressing both parasitic side reactions and dendrite formation. More importantly, an ultralong cycling life of 3115 h in the Zn||Zn symmetric cell at a current density of 0.5 mA cm-2 is achieved with the NMF additive. Practically, the Zn||PANI full cell utilizing NMF electrolyte shows better rate and cycling performance compared to the pristine ZnSO4 aqueous electrolyte. This work provides useful insights for the development of high-performance aqueous metal batteries.

2.
Biosensors (Basel) ; 14(1)2024 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-38248423

RESUMEN

As membrane-mediated antibiotic resistance continues to evolve in Gram-positive bacteria, the development of new approaches to elucidate the membrane properties involved in antibiotic resistance has become critical. Membrane vesicles (MVs) secreted by the cytoplasmic membrane of Gram-positive bacteria contain native components, preserving lipid and protein diversity, nucleic acids, and sometimes virulence factors. Thus, MV-derived membrane platforms present a great model for Gram-positive bacterial membranes. In this work, we report the development of a planar bacterial cytoplasmic membrane-based biosensor using MVs isolated from the Bacillus subtilis WT strain that can be coated on multiple surface types such as glass, quartz crystals, and polymeric electrodes, fostering the multimodal assessment of drug-membrane interactions. Retention of native membrane components such as lipoteichoic acids, lipids, and proteins is verified. This biosensor replicates known interaction patterns of the antimicrobial compound, daptomycin, with the Gram-positive bacterial membrane, establishing the applicability of this platform for carrying out biophysical characterization of the interactions of membrane-acting antibiotic compounds with the bacterial cytoplasmic membrane. We report changes in membrane viscoelasticity and permeability that correspond to partial membrane disruption when calcium ions are present with daptomycin but not when these ions are chelated. This biomembrane biosensing platform enables an assessment of membrane biophysical characteristics during exposure to antibiotic drug candidates to aid in identifying compounds that target membrane disruption as a mechanism of action.


Asunto(s)
Antibacterianos , Daptomicina , Antibacterianos/farmacología , Bacterias Grampositivas , Membrana Celular , Iones
3.
Langmuir ; 38(29): 8773-8782, 2022 07 26.
Artículo en Inglés | MEDLINE | ID: mdl-35748045

RESUMEN

The rise of antibiotic resistance is a growing worldwide human health issue, with major socioeconomic implications. An understanding of the interactions occurring at the bacterial membrane is crucial for the generation of new antibiotics. Supported lipid bilayers (SLBs) made from reconstituted lipid vesicles have been used to mimic these membranes, but their utility has been restricted by the simplistic nature of these systems. A breakthrough in the field has come with the use of outer membrane vesicles derived from Gram-negative bacteria to form SLBs, thus providing a more physiologically relevant system. These complex bilayer systems hold promise but have not yet been fully characterized in terms of their composition, ratio of natural to synthetic components, and membrane protein content. Here, we use correlative atomic force microscopy (AFM) with structured illumination microscopy (SIM) for the accurate mapping of complex lipid bilayers that consist of a synthetic fraction and a fraction of lipids derived from Escherichia coli outer membrane vesicles (OMVs). We exploit the high resolution and molecular specificity that SIM can offer to identify areas of interest in these bilayers and the enhanced resolution that AFM provides to create detailed topography maps of the bilayers. We are thus able to understand the way in which the two different lipid fractions (natural and synthetic) mix within the bilayers, and we can quantify the amount of bacterial membrane incorporated into the bilayer. We prove the system's tunability by generating bilayers made using OMVs engineered to contain a green fluorescent protein (GFP) binding nanobody fused with the porin OmpA. We are able to directly visualize protein-protein interactions between GFP and the nanobody complex. Our work sets the foundation for accurately understanding the composition and properties of OMV-derived SLBs to generate a high-resolution platform for investigating bacterial membrane interactions for the development of next-generation antibiotics.


Asunto(s)
Membrana Externa Bacteriana , Membrana Dobles de Lípidos , Antibacterianos , Escherichia coli , Proteínas Fluorescentes Verdes , Humanos , Membrana Dobles de Lípidos/química , Microscopía de Fuerza Atómica
4.
ACS Appl Mater Interfaces ; 14(13): 15799-15810, 2022 Apr 06.
Artículo en Inglés | MEDLINE | ID: mdl-35344337

RESUMEN

Photosynthetic semiconductor biohybrids (PSBs) convert light energy to chemical energy through photo-driven charge transfer from nanocrystals to microorganisms that perform bioreactions of interest. Initial proof-of-concept PSB studies with an emphasis on enhanced CO2 conversion have been encouraging; however, bringing the broad prospects of PSBs to fruition is contingent on establishing a firm fundamental understanding of underlying interfacial charge transfer processes. We introduce a bioelectronic platform that reduces the complexity of PSBs by focusing explicitly on interactions between colloidal quantum dots (QDs), microbial outer membranes, and native, small-molecule redox mediators. Our model platform employs a standard three-electrode electrochemical cell with supported outer membranes of Pseudomonas aeruginosa, pyocyanin redox mediators, and semiconducting CdSe QDs dispersed in an aqueous electrolyte. We present a comprehensive electrochemical analysis of this platform via electrochemical impedance spectroscopy (EIS), cyclic voltammetry (CV), and chronoamperometry (CA). EIS reveals the formation and electronic properties of supported outer membrane films. CV reveals the electrochemically active surface area of P. aeruginosa outer membranes and that pyocyanin is the sole species that performs redox with these outer membranes under sweeping applied potential. CA demonstrates that photoexcited charge transfer in this system is driven by the reduction of pyocyanin at the QD surface followed by diffusion of reduced pyocyanin through the outer membrane. The broad applicability of this platform across many bacterial species, QD architectures, and controlled environmental conditions affords the possibility to define design principles for future PSB systems to synergistically integrate concurrent advances in genetically engineered organisms and inorganic nanomaterials.


Asunto(s)
Nanoestructuras , Puntos Cuánticos , Electrodos , Oxidación-Reducción , Semiconductores
5.
Ann Med Surg (Lond) ; 74: 103340, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-35198172

RESUMEN

BACKGROUND: Hyponatremia is a prevalent electrolyte abnormality amongst hospitalized patients. The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is a common cause of hyponatremia. Minimal literature described an association between SIADH and brucellosis. This paper aimed to systematically review the literature to synthesize the prevalence of SIADH in brucellosis patients. METHODS: We comprehensively searched PubMed, EMBASE, and Google scholar for observational studies examining the prevalence of SIADH in brucellosis patients. There were no age, language, or date limitations. We used a prevalence meta-analysis using the random-effects model with double arcsine and back transformation. I squared (I2) was used to determine heterogeneity. The MetaXl software was used for statistical analysis. RESULTS: Three observational studies met our inclusion criteria. The reported prevalence of SIADH in the constituent studies ranged from 3 to 56%. The quantitative synthesis, encompassing 306 patients' data, revealed a pooled SIADH prevalence of 20% (95% CI 0.00-52%, I2 96%). The quality assessment revealed a moderate quality of included studies. The results were heterogeneous, as depicted by a high I2. DISCUSSION AND CONCLUSION: The results from this review revealed a relatively high prevalence of SIADH of 20% in patients with brucellosis. Thus, hyponatremia in patients with chronic fever should prompt SIADH and brucellosis workup, particularly in endemic brucellosis areas. Likewise, patients with brucellosis merit hyponatremia screening. More extensive studies are needed to ascertain the exact prevalence of hyponatremia and SIADH in this patient cohort and their impact on the diagnosis and the overall prognosis.

6.
Biosens Bioelectron ; 204: 114045, 2022 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-35180690

RESUMEN

Antibiotic resistance is a growing global health concern due to the decreasing number of antibiotics available for therapeutic use as more drug-resistant bacteria develop. Changes in the membrane properties of Gram-negative bacteria can influence their response to antibiotics and give rise to resistance. Thus, understanding the interactions between the bacterial membrane and antibiotics is important for elucidating microbial membrane properties to use for designing novel antimicrobial drugs. To study bacterial membrane-antibiotic interactions, we created a surface-supported planar bacterial outer membrane model on an optically-transparent, conducting polymer surface (poly (3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS)). This model enables membrane characterization using fluorescence microscopy and electrochemical impedance spectroscopy (EIS). The membrane platform is fabricated using outer membrane vesicles (OMVs) isolated from clinically relevant Gram-negative bacteria, enterohemorrhagic Escherichia coli. This approach enables us to mimic the native components of the bacterial membrane by incorporating native lipids, membrane proteins, and lipopolysaccharides. Using EIS, we determined membrane impedance and captured membrane-antibiotic interactions using the antibiotics polymyxin B, bacitracin, and meropenem. This sensor platform incorporates aspects of the biological complexity found in bacterial outer membranes and, by doing so, offers a powerful, biomimetic approach to the study of antimicrobial drug interactions.


Asunto(s)
Técnicas Biosensibles , Escherichia coli , Antibacterianos/metabolismo , Antibacterianos/farmacología , Proteínas de la Membrana Bacteriana Externa , Impedancia Eléctrica , Escherichia coli/química , Bacterias Gramnegativas
7.
ACS Biomater Sci Eng ; 7(12): 5585-5597, 2021 12 13.
Artículo en Inglés | MEDLINE | ID: mdl-34802228

RESUMEN

Cancer-derived exosomes (cEXOs) facilitate transfer of information between tumor and human primary stromal cells, favoring cancer progression. Although the mechanisms used during this information exchange are still not completely understood, it is known that binding is the initial contact established between cEXOs and cells. Hence, studying binding and finding strategies to block it are of great therapeutic value. However, such studies are challenging for a variety of reasons, including the need for human primary cell culture, the difficulty in decoupling and isolating binding from internalization and cargo delivery, and the lack of techniques to detect these specific interactions. In this work, we created a supported biomimetic stem cell membrane incorporating membrane components from human primary adipose-derived stem cells (ADSCs). We formed the supported membrane on glass and on multielectrode arrays to offer the dual option of optical or electrical detection of cEXO binding to the membrane surface. Using our platform, we show that cEXOs bind to the stem cell membrane and that binding is blocked when an antibody to integrin ß1, a component of ADSC surface, is exposed to the membrane surface prior to cEXOs. To test the biological outcome of blocking this interaction, we first confirm that adding cEXOs to cultured ADSCs leads to the upregulation of vascular endothelial growth factor, a measure of proangiogenic activity. Next, when ADSCs are first blocked with anti-integrin ß1 and then exposed to cEXOs, the upregulation of proangiogenic activity and cell proliferation are significantly reduced. This biomimetic membrane platform is the first cell-free label-free in vitro platform for the recapitulation and study of cEXO binding to human primary stem cells with potential for therapeutic molecule screening as it is compatible with scale-up and multiplexing.


Asunto(s)
Exosomas , Neoplasias , Biomimética , Humanos , Células Madre , Factor A de Crecimiento Endotelial Vascular
9.
ACS Infect Dis ; 7(9): 2707-2722, 2021 09 10.
Artículo en Inglés | MEDLINE | ID: mdl-34227387

RESUMEN

Antibiotic resistance is a growing global health concern that has been increasing in prevalence over the past few decades. In Gram-negative bacteria, the outer membrane is an additional barrier through which antibiotics must traverse to kill the bacterium. In addition, outer membrane features and properties, like membrane surface charge, lipopolysaccharide (LPS) length, and membrane porins, can be altered in response to antibiotics and therefore, further mediate resistance. Model membranes have been used to mimic bacterial membranes to study antibiotic-induced membrane changes but often lack the compositional complexity of the actual outer membrane. Here, we developed a surface-supported membrane platform using outer membrane vesicles (OMVs) from clinically relevant Gram-negative bacteria and use it to characterize membrane biophysical properties and investigate its interaction with antibacterial compounds. We demonstrate that this platform maintains critical features of outer membranes, like fluidity, while retaining complex membrane components, like OMPs and LPS, which are central to membrane-mediated antibiotic resistance. This platform offers a non-pathogenic, cell-free surface to study such phenomena that is compatible with advanced microscopy and surface characterization tools like quartz crystal microbalance. We confirm these OMV bilayers recapitulate membrane interactions (or lack thereof) with the antibiotic compounds polymyxin B, bacitracin, and vancomycin, validating their use as representative models for the bacterial surface. By forming OMV bilayers from different strains, we envision that this platform could be used to investigate underlying biophysical differences in outer membranes leading to resistance, to screen and identify membrane-active antibiotics, or for the development of phage technologies targeting a particular membrane surface component.


Asunto(s)
Antibacterianos , Membrana Externa Bacteriana , Antibacterianos/farmacología , Proteínas de la Membrana Bacteriana Externa/metabolismo , Bacterias Gramnegativas/metabolismo , Porinas
10.
Nanomaterials (Basel) ; 11(1)2021 Jan 12.
Artículo en Inglés | MEDLINE | ID: mdl-33445545

RESUMEN

Ocular diseases can deteriorate vision to the point of blindness and thus can have a major impact on the daily life of an individual. Conventional therapies are unable to provide absolute therapy for all ocular diseases due to the several limitations during drug delivery across the blood-retinal barrier, making it a major clinical challenge. With recent developments, the vast number of publications undergird the need for nanotechnology-based drug delivery systems in treating ocular diseases. The tool of nanotechnology provides several essential advantages, including sustained drug release and specific tissue targeting. Additionally, comprehensive in vitro and in vivo studies have suggested a better uptake of nanoparticles across ocular barriers. Nanoparticles can overcome the blood-retinal barrier and consequently increase ocular penetration and improve the bioavailability of the drug. In this review, we aim to summarize the development of organic and inorganic nanoparticles for ophthalmic applications. We highlight the potential nanoformulations in clinical trials as well as the products that have become a commercial reality.

11.
Biomed Pharmacother ; 132: 110908, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33254431

RESUMEN

Ginkgolide A is a highly active platelet activating factor antagonist cage molecule which was isolated from the leaves of the Ginkgo biloba L. It is known for its inflammatory and immunological potentials. This review aims to sketch a current scenario on its therapeutic activities on the basis of scientific reports in the databases. A total 30 articles included in this review suggests that ginkgolide A has many important biological activities, including anti-inflammatory, anticancer, anxiolytic-like, anti-atherosclerosis and anti-atherombosis, neuro- and hepatoprotective effects. There is a lack of its toxicological (e.g. toxicity, cytotoxicity, genotoxicity and mutagenitcity) profile. In conclusion, ginkgolide A may be one of the potential therapeutic lead compounds, especially for the treatment of cardiovascular, hepatological, and neurological diseases and disorders. More studies are necessary on this hopeful therapeutic agent.


Asunto(s)
Ginkgo biloba , Ginkgólidos/farmacología , Ginkgólidos/uso terapéutico , Lactonas/farmacología , Lactonas/uso terapéutico , Factor de Activación Plaquetaria/antagonistas & inhibidores , Animales , Ansiolíticos/aislamiento & purificación , Ansiolíticos/uso terapéutico , Antiinflamatorios/aislamiento & purificación , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/uso terapéutico , Ginkgólidos/aislamiento & purificación , Humanos , Lactonas/aislamiento & purificación , Hojas de la Planta , Factor de Activación Plaquetaria/metabolismo
12.
Diabetes Metab Syndr Obes ; 13: 3807-3819, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33116728

RESUMEN

BACKGROUND AND AIM: Type 2 diabetes mellitus (DM) is the most common single cause of the end-stage renal disease (ESRD). Cyclophilin A (CyPA) is an 18-kD protein. The connection between diabetic nephropathy (DN) and the secreted form of CyPA (sCyPA) has been elucidated in this study that aims to investigate sCyPA correlation with renal dysfunction. MATERIALS AND METHODS: Thirty-four male adult Wistar rats weighing 180-220 g were used. Animals were divided into a study group and a control group, 17 rats in each. Streptozotocin (STZ) and nicotine amide were used to damage some pancreatic cells for induction of type 2 DM. Comparison was made between the study and the control groups. Moreover, a comparison was made between the members of the study group before and after induction of DN. RESULTS: The rat model that exhibited a higher concentration of urinary sCyPA was detected early in the eighth week. There was a significantly higher level of 24-h urinary CyPA in the study group compared to the control group (p-value=0.004) and there was a significant elevation in the 24-h urinary Cyp-A in the study group after injection of STZ compared to the values before injection (p-value <0.001). Immunohistochemical analysis of renal tissue revealed that the mean expression of CyPA was higher in the study group than in the control group. For the urinary 24-h CYP-A, using a cutoff of 1.15 ng/mL, the accuracy was 72.4%, sensitivity was (77.8%) and specificity was (67%). CONCLUSION: According to this animal study, we proved that CyPA is a valuable marker for DN. It is a more sensitive, noninvasive and rapid biomarker for early detection of any renal affection in human diabetic patients.

13.
Molecules ; 25(16)2020 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-32824120

RESUMEN

Neurodegenerative diseases (NDDs) are chronic conditions that have drawn robust interest from the scientific community. Phytotherapeutic agents are becoming an important source of chemicals for the treatment and management of NDDs. Various secondary metabolites have been isolated from Melicope lunu-ankenda plant leaves, including phenolic acid derivatives. However, their neuroprotective activity remains unclear. Thus, the aim of this study is to elucidate the in vitro neuroprotective activity of 7-geranyloxycinnamic acid isolated from Melicope lunu-ankenda leaves. The neuroprotective activity was evaluated in differentiated human neuroblastoma (SH-SY5Y) cells by monitoring cell viability using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). Moreover, the potential to impair apoptosis in differentiated cells was investigated employing the Annexin V-FITC assay, acridine orange and propidium iodide (AO/PI) staining, and fluorescence microscopy. Morphological assessment and ultrastructural analysis were performed using scanning and transmission electron microscopy to evaluate the effect of 7-geranyloxycinnamic acid on surface morphology and internal features of the differentiated cells. Pre-treatment of neuronal cells with 7-geranyloxycinnamic acid significantly protected the differentiated SH-SY5Y cells against H2O2-induced apoptosis. Cytoskeleton and cytoplasmic inclusion were similarly protected by the 7-geranyloxycinnamic acid treatment. The present findings demonstrate the neuroprotective potential of 7-geranyloxycinnamic acid against H2O2-induced neurotoxicity in neuronal cells, which is an established hallmark of neuronal disorders.


Asunto(s)
Cinamatos/química , Neuroblastoma/tratamiento farmacológico , Fármacos Neuroprotectores/farmacología , Extractos Vegetales/farmacología , Hojas de la Planta/química , Rutaceae/química , Apoptosis , Supervivencia Celular , Humanos , Neuroblastoma/patología , Estrés Oxidativo/efectos de los fármacos , Células Tumorales Cultivadas
14.
Artículo en Inglés | MEDLINE | ID: mdl-32340361

RESUMEN

Middle East respiratory syndrome coronavirus (MERS-CoV) is an emerging zoonotic coronavirus that has a tendency to cause significant healthcare outbreaks among patients with serious comorbidities. We analyzed hospital data from the MERS-CoV outbreak in King Abdulaziz Medical Center, Riyadh, Saudi Arabia, June-August 2015 using the susceptible-exposed-infectious-recovered (SEIR) ward transmission model. The SEIR compartmental model considers several areas within the hospital where transmission occurred. We use a system of ordinary differential equations that incorporates the following units: emergency department (ED), out-patient clinic, intensive care unit, and hospital wards, where each area has its own carrying capacity and distinguishes the transmission by three individuals in the hospital: patients, health care workers (HCW), or mobile health care workers. The emergency department, as parameterized has a large influence over the epidemic size for both patients and health care workers. Trend of the basic reproduction number (R0), which reached a maximum of 1.39 at the peak of the epidemic and declined to 0.92 towards the end, shows that until added hospital controls are introduced, the outbreak would continue with sustained transmission between wards. Transmission rates where highest in the ED, and mobile HCWs were responsible for large part of the outbreak.


Asunto(s)
Infecciones por Coronavirus/transmisión , Brotes de Enfermedades , Hospitales , Control de Infecciones , Coronavirus del Síndrome Respiratorio de Oriente Medio/patogenicidad , Número Básico de Reproducción , Infecciones por Coronavirus/prevención & control , Humanos , Arabia Saudita/epidemiología
15.
Front Mol Biosci ; 7: 624494, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33521059

RESUMEN

Cancer is a multifactorial disease characterized by complex molecular landscape and altered cell pathways that results in an abnormal cell growth. Natural compounds are target-specific and pose a limited cytotoxicity; therefore, can aid in the development of new therapeutic interventions for the treatment of this versatile disease. Berberine is a member of the protoberberine alkaloids family, mainly present in the root, stem, and bark of various trees, and has a reputed anticancer activity. Nonetheless, the limited bioavailability and low absorption rate are the two major hindrances following berberine administration as only 0.5% of ingested berberine absorbed in small intestine while this percentage is further decreased to 0.35%, when enter in systemic circulation. Nano-based formulation is believed to be an ideal candidate to increase absorption percentage as at nano scale level, compounds can absorb rapidly in gut. Nanotechnology-based therapeutic approaches have been implemented to overcome such problems, ultimately promoting a higher efficacy in the treatment of a plethora of diseases. This review present and critically discusses the anti-proliferative role of berberine and the nanotechnology-based therapeutic strategies used for the nano-scale delivery of berberine. Finally, the current approaches and promising perspectives of latest delivery of this alkaloid are also critically analyzed and discussed.

16.
ACS Biomater Sci Eng ; 6(7): 3945-3956, 2020 07 13.
Artículo en Inglés | MEDLINE | ID: mdl-33463350

RESUMEN

Extracellular vesicles (EVs) are membrane-encapsulated particles secreted by eukaryotic cells that stimulate cell communication and horizontal cargo exchange. EV interactions with stromal cells can result in molecular changes in the recipient cell and, in some cases, lead to disease progression. However, mechanisms leading to these changes are poorly understood. A few model systems are available for studying the outcomes of surface interactions between EV membranes with stromal cells. Here, we created a hybrid supported bilayer incorporating EVs membrane material, called an extracellular vesicle supported bilayer, EVSB. Using EVSBs, we investigated the surface interactions between breast cancer EVs and adipose-derived stem cells (ADSCs) by culturing ADSCs on EVSBs and analyzing cell adhesion, spreading, viability, vascular endothelial growth factor (VEGF) secretion, and myofibroblast differentiation. Results show that cell viability, adhesion, spreading, and proangiogenic activity were enhanced, conditions that promote oncogenic activity, but cell differentiation was not. This model system could be used to develop therapeutic strategies to limit EV-ADSC interactions and proangiogenic conditions. Finally, this model system is not limited to the study of cancer but can be used to study surface interactions between EVs from any origin and any target cell to investigate EV mechanisms leading to cellular changes in other diseases.


Asunto(s)
Vesículas Extracelulares , Factor A de Crecimiento Endotelial Vascular , Comunicación Celular , Diferenciación Celular , Humanos , Células del Estroma
17.
Molecules ; 24(17)2019 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-31461914

RESUMEN

Plant natural compounds have great potential as alternative medicines for preventing and treating diseases. Melicope lunu-ankenda is one Melicope species (family Rutaceae), which is widely used in traditional medicine, consumed as a salad and a food seasoning. Consumption of different parts of this plant has been reported to exert different biological activities such as antioxidant and anti-inflammatory qualities, resulting in a protective effect against several health disorders including neurodegenerative diseases. Various secondary metabolites such as phenolic acid derivatives, flavonoids, coumarins and alkaloids, isolated from the M. lunu-ankenda plant, were demonstrated to have neuroprotective activities and also exert many other beneficial biological effects. A number of studies have revealed different neuroprotective mechanisms for these secondary metabolites. This review summarizes the most significant and recent studies for neuroprotective activity of M. lunu-ankenda major secondary metabolites in neurodegenerative diseases.


Asunto(s)
Fitoquímicos/farmacología , Rutaceae/química , Metabolismo Secundario , Animales , Antiinflamatorios/química , Antiinflamatorios/farmacología , Antioxidantes/química , Antioxidantes/farmacología , Humanos , Medicina Tradicional , Estructura Molecular , Fármacos Neuroprotectores/química , Fármacos Neuroprotectores/farmacología , Fitoquímicos/química
18.
Commun Biol ; 1: 220, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30534612

RESUMEN

Cationic charge and hydrophobicity have long been understood to drive the potency and selectivity of antimicrobial peptides (AMPs). However, these properties alone struggle to guide broad success in vivo, where AMPs must differentiate bacterial and mammalian cells, while avoiding complex barriers. New parameters describing the biophysical processes of membrane disruption could provide new opportunities for antimicrobial optimization. In this work, we utilize oligothioetheramides (oligoTEAs) to explore the membrane-targeting mechanism of oligomers, which have the same cationic charge and hydrophobicity, yet show a unique ~ 10-fold difference in antibacterial potency. Solution-phase characterization reveals little difference in structure and dynamics. However, fluorescence microscopy of oligomer-treated Staphylococcus aureus mimetic membranes shows multimeric lipid aggregation that correlates with biological activity and helps establish a framework for the kinetic mechanism of action. Surface plasmon resonance supports the kinetic framework and supports lipid aggregation as a driver of antimicrobial function.

19.
Adv Exp Med Biol ; 1092: 235-251, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30368756

RESUMEN

Platelets can be considered as the "guardian of hemostasis" where their main function is to maintain vascular integrity. In pathological conditions, the hemostatic role of platelets may be hijacked to stimulate disease progression. In 1865, Armand Trousseau was a pioneer in establishing the platelet-cancer metastasis relationship, which he eventually termed as Trousseau's Syndrome to describe the deregulation of the hemostasis-associated pathways induced by cancer progression (Varki, Blood. 110(6):1723-9, 2007). Since these early studies, there has been an increase in experimental evidence not only to elucidate the role of platelets in cancer metastasis but also to create novel cancer therapies by targeting the platelet's impact in metastasis. In this chapter, we discuss the contribution of platelets in facilitating tumor cell transit from the primary tumor to distant metastatic sites as well as novel cancer therapies based on platelet interactions.


Asunto(s)
Plaquetas , Sistemas de Liberación de Medicamentos , Metástasis de la Neoplasia/tratamiento farmacológico , Neoplasias/tratamiento farmacológico , Hemostasis , Humanos , Masculino
20.
Oncotarget ; 9(53): 30053-30065, 2018 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-30046387

RESUMEN

Ovarian cancer is the most aggressive female reproductive tract tumours. Taxane (paclitaxel; TX) is widely used for ovarian cancer treatment. However, ovarian cancers often acquire chemoresistance. MicroRNAs (miR) have been reported to mediate many tumours'chemoresistance. We investigated the role of miR-363 in the chemoresistance of the ovarian cancer cell line, KF, and its TX-resistant derivative (KF-TX) cells. QRT-PCR indicated that miR-363 was upregulated in KF-TX cells, and introduction of miR-363 into sensitive ovarian cancer cells confers TX-resistance and significantly inhibited the expression of the Hippo member, LATS2, as indicated by viability, clonogenic assay and expression analysis. Furthermore, we validated the role of LATS2 in TX-response by sh-based silencing, which also confers TX-resistance to the ovarian cancer cells. On the other hand, specific inhibitor against miR-363 restored the response to TX in the resistant cells. In addition, miR-363 was found to bind to the 3'-UTR of LATS2 mRNA, confirming that miR-363 directly targets LATS2 as indicated by dual luciferase assay. RT-PCR-based evaluation of miR-363 in a panel of human ovarian tumours revealed its upregulation in most of the tumour tissues identified as resistant while it was downregulated in most of the tissues identified as sensitive ones. Moreover, higher levels of miR-363 in human ovarian cancer specimens were significantly correlated with TX chemoresistance. Taken together, our study reveals the involvement of miR-363 in chemoresistance by targeting LATS2 in ovarian cancers, raising the possibility that combination therapy with a miR-363 inhibitor and TX may increase TX efficacy and reduce the chance of TX-resistance.

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