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Infections caused by viruses as the smallest infectious agents, pose a major threat to global public health. Viral infections utilize different host mechanisms to facilitate their own propagation and pathogenesis. MicroRNAs (miRNAs), as small noncoding RNA molecules, play important regulatory roles in different diseases, including viral infections. They can promote or inhibit viral infection and have a pro-viral or antiviral role. Also, viral infections can modulate the expression of host miRNAs. Furthermore, viruses from different families evade the host immune response by producing their own miRNAs called viral miRNAs (v-miRNAs). Understanding the replication cycle of viruses and their relation with host miRNAs and v-miRNAs can help to find new treatments against viral infections. In this review, we aim to outline the structure, genome, and replication cycle of various viruses including hepatitis B, hepatitis C, influenza A virus, coronavirus, human immunodeficiency virus, human papillomavirus, herpes simplex virus, Epstein-Barr virus, Dengue virus, Zika virus, and Ebola virus. We also discuss the role of different host miRNAs and v-miRNAs and their role in the pathogenesis of these viral infections.
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Gene therapy is a therapeutic option for mitigating diseases that do not respond well to pharmacological therapy. This type of therapy allows for correcting altered and defective genes by transferring nucleic acids to target cells. Notably, achieving a desirable outcome is possible by successfully delivering genetic materials into the cell. In-vivo gene transfer strategies use two major classes of vectors, namely viral and nonviral. Both of these systems have distinct pros and cons, and the choice of a delivery system depends on therapeutic objectives and other considerations. Safe and efficient gene transfer is the main feature of any delivery system. Spherical nucleic acids (SNAs) are nanotechnology-based gene delivery systems (i.e., non-viral vectors). They are three-dimensional structures consisting of a hollow or solid spherical core nanoparticle that is functionalized with a dense and highly organized layer of oligonucleotides. The unique structural features of SNAs confer them a high potency in internalization into various types of tissue and cells, a high stability against nucleases, and efficay in penetrating through various biological barriers (such as the skin, blood-brain barrier, and blood-tumor barrier). SNAs also show negligible toxicity and trigger minimal immune response reactions. During the last two decades, all these favorable physicochemical and biological attributes have made them attractive vehicles for drug and nucleic acid delivery. This article discusses the unique structural properties, types of SNAs, and also optimization mechanisms of SNAs. We also focus on recent advances in the synthesis of gene delivery nanoplatforms based on the SNAs.
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Técnicas de Transferencia de Gen , Terapia Genética , Nanopartículas , Ácidos Nucleicos , Humanos , Ácidos Nucleicos/química , Animales , Terapia Genética/métodos , Nanopartículas/química , Nanotecnología/métodosRESUMEN
Nanovaccines have been designed to overcome the limitations associated with conventional vaccines. Effective delivery methods such as engineered carriers or smart nanoparticles (NPs) are critical requisites for inducing self-tolerance and optimizing vaccine immunogenicity with minimum side effects. NPs can be used as adjuvants, immunogens, or nanocarriers to develop nanovaccines for efficient antigen delivery. Multiloaded nanovaccines carrying multiple tumor antigens along with immunostimulants can effectively increase immunity against tumor cells. They can be biologically engineered to boost interactions with dendritic cells and to allow a gradual and constant antigen release. Modifying NPs surface properties, using high-density lipoprotein-mimicking nanodiscs, and developing nano-based artificial antigen-presenting cells such as dendritic cell-derived-exosomes are amongst the new developed technologies to enhance antigen-presentation and immune reactions against tumor cells. The present review provides an overview on the different perspectives, improvements, and barriers of successful clinical application of current cancer therapeutic and vaccination options. The immunomodulatory effects of different types of nanovaccines and the nanoparticles incorporated into their structure are described. The advantages of using nanovaccines to prevent and treat common illnesses such as AIDS, malaria, cancer and tuberculosis are discussed. Further, potential paths to develop optimal cancer vaccines are described. Given the immunosuppressive characteristics of both cancer cells and the tumor microenvironment, applying immunomodulators and immune checkpoint inhibitors in combination with other conventional anticancer therapies are necessary to boost the effectiveness of the immune response.
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Antígenos de Neoplasias , Vacunas contra el Cáncer , Inmunoterapia , Nanopartículas , Neoplasias , Humanos , Inmunoterapia/métodos , Neoplasias/inmunología , Neoplasias/terapia , Neoplasias/tratamiento farmacológico , Nanopartículas/administración & dosificación , Vacunas contra el Cáncer/administración & dosificación , Vacunas contra el Cáncer/inmunología , Antígenos de Neoplasias/inmunología , Antígenos de Neoplasias/administración & dosificación , Animales , Terapia Combinada , Sistemas de Liberación de Medicamentos/métodos , NanovacunasRESUMEN
Due to high mortality rates, typhoid fever still is one of the major health problems in the world, particularly in developing countries. The lack of highly specific and sensitive diagnostic tests and the great resemblance of typhoid fever symptoms to other diseases made the false-negative diagnosis a major challenge in typhoid fever management. Hence, we decided to design a Surface Plasmon Resonance (SPR) based biosensor for specific detection of Salmonella typhi through DNA hybridization. The results showed that the 10 nM of the synthetic target sequence, as well as 1 nM of PCR product, were the lowest feasible detected concentrations by the designed biosensor. This genosensor was also found to significantly distinguish the complementary sequence with the accuracy of one base mismatch sequence. The surface of the chip can be regenerated with NaOH solution and used for consecutive diagnosis. Therefore, the function of the designed biosensor indicates its high potential for Salmonella typhi detection practice.
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Técnicas Biosensibles , Fiebre Tifoidea , Humanos , Salmonella typhi/genética , Fiebre Tifoidea/diagnóstico , Resonancia por Plasmón de Superficie/métodos , Oligonucleótidos , Sensibilidad y EspecificidadRESUMEN
Spinal cord injury (SCI) has devastating effects on a person's physical, social, and professional well-being. It is a life-altering neurological condition that significantly impacts individuals and their caregivers on a socioeconomic level. Recent advancements in medical therapy have greatly improved the diagnosis, stability, survival rates, and overall well-being of SCI patients. However, there are still limited options available for enhancing neurological outcomes in these patients. The complex pathophysiology of SCI, along with the numerous biochemical and physiological changes that occur in the damaged spinal cord, contribute to this gradual improvement. Currently, there are no therapies that offer the possibility of recovery for SCI, although several therapeutic approaches are being developed. However, these therapies are still in the early stages and have not yet demonstrated effectiveness in repairing the damaged fibers, which hinders cellular regeneration and the full restoration of motor and sensory functions. Considering the importance of nanotechnology and tissue engineering in treating neural tissue injuries, this review focuses on the latest advancements in nanotechnology for SCI therapy and tissue healing. It examines research articles from the PubMed database that specifically address SCI in the field of tissue engineering, with an emphasis on nanotechnology as a therapeutic approach. The review evaluates the biomaterials used for treating this condition and the techniques employed to create nanostructured biomaterials.
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Nanomedicina , Traumatismos de la Médula Espinal , Humanos , Traumatismos de la Médula Espinal/tratamiento farmacológico , Materiales Biocompatibles/uso terapéutico , NanotecnologíaRESUMEN
New selenopheno[2,3-e][1,2,4]triazolo[1,5-c]pyrimidine derivatives have been synthesized via Dimroth rearrangement by cyclocondensation of 7-cyano-4-hydrazinyl-6-(pyrrolidin-1-yl)selenopheno[3,2-d]pyrimidine with electrophilic carbons of either orthoesters in acetic acid or carbon disulfide in pyridine followed by S-alkylation. All the newly synthesized products have been structurally elucidated. The in vitro anticancer screening of the tricyclic Se-containing heterocycles was accomplished against human breast carcinoma MCF-7 cancerous cell line and L929 cells. Anticancer results revealed that the S-hexyl-substituted compound with an IC50 value of 158.9 µM in 72 h was foremost among others in cytotoxic potency. In the following order, S-pentyl and S-ethyl-substituted derivatives with IC50 values of 216.1 and 396.5 µM were second and third efficient compounds as in anticancer activity, respectively. The inhibitory effects of the mentioned compounds were less on the growth of L929 cells.
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Antineoplásicos , Neoplasias de la Mama , Antineoplásicos/farmacología , Neoplasias de la Mama/tratamiento farmacológico , Línea Celular Tumoral , Proliferación Celular , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Femenino , Humanos , Estructura Molecular , Pirimidinas/farmacología , Relación Estructura-ActividadRESUMEN
Nanotechnology has provided great opportunities for managing neoplastic conditions at various levels, from preventive and diagnostic to therapeutic fields. However, when it comes to clinical application, nanoparticles (NPs) have some limitations in terms of biological stability, poor targeting, and rapid clearance from the body. Therefore, biomimetic approaches, utilizing immune cell membranes, are proposed to solve these issues. For example, macrophage or neutrophil cell membrane coated NPs are developed with the ability to interact with tumor tissue to suppress cancer progression and metastasis. The functionality of these particles largely depends on the surface proteins of the immune cells and their preserved function during membrane extraction and coating process on the NPs. Proteins on the outer surface of immune cells can render a wide range of activities to the NPs, including prolonged blood circulation, remarkable competency in recognizing antigens for enhanced targeting, better cellular interactions, gradual drug release, and reduced toxicity in vivo. In this review, nano-based systems coated with immune cells-derived membranous layers, their detailed production process, and the applicability of these biomimetic systems in cancer treatment are discussed. In addition, future perspectives and challenges for their clinical translation are also presented.
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Materiales Biomiméticos , Nanopartículas , Neoplasias , Biomimética , Membrana Celular , Humanos , Neoplasias/terapia , FototerapiaRESUMEN
BACKGROUND: Loss of skin integrity due to injury, burning, or illness makes the development of new treatment options necessary. Skin tissue engineering provides some solutions for these problems. OBJECTIVE: The potential of a biodegradable star-shaped copolymer [Poly(CLâCOâLA)-b-PEG] and penta-block copolymer hydrogel (PNIPAAm-PCL-PEG-PCL-PNIPAAm) was assessed for skin tissue engineering applications. METHODS: Two copolymers were synthesized for cellular culture scaffolds and their mechanical properties were compared. The resulting star-shaped copolymer and thermosensitive penta-block copolymer were characterized using Fourier transform infrared and nuclear magnetic resonance spectroscopy. The crystallizability of the two copolymers was analyzed using X-ray diffraction. The resulting thermosensitive penta-block copolymer was evaluated by differential thermal analysis, differential scanning calorimetry and thermogravimetric analysis. Scanning electron microscopy and in vitro degradation of the polymer network in phosphate buffer solutions (pH 7.4) at 37°C were also examined. The pore size of the gels was calculated with Image Analyzer software. Finally, the cytotoxic, morphological, and gene expression effects of copolymers on the skin fibroblast were evaluated. RESULTS: The experiments showed that the PNIPAAm-PCL-PEG-PCL-PNIPAAm polymer with the right composition and the expected molecular weight was achieved. The hydrogel had less crystallizability compared with its precursors. The resulting thermosensitive hydrogel had a three-dimensional structure with interconnected pores that mimicked the extracellular matrix. The control of the degradability rate can be possible by weight percent changes. The pore size correlated with the polymer concentration in aqueous solution and the pore sizes of the 20 wt% hydrogel were better for fibroblast cultivation than those of the 10 wt% hydrogel. Cell proliferation on the 20% gel was more than that of the 10% gel. The hydrogel not only preserved the viability and phenotypical morphology of the entrapped cells but also stimulated the initial cell-cell interactions and proliferation of fibroblasts. The hydrogel did not influence cell conformation and this property of the polymer underlined its safety. Cells seeded on this copolymer showed a normal and spear shape and formed a focal adhesion with the hydrogel surface. Notably, the hydrogel increased collagen I α1 and collagen III mRNAs expression. CONCLUSION: Due to the low molecular weight and poor mechanical strength of the star-shaped copolymer, it was not considered for fabrication of the scaffolds for wound healing. The biodegradable, biocompatible, injectable and thermosensitive PNIPAAm-PCL-PEG-PCL-PNIPAAm hydrogel in 20 wt% demonstrated a desirable potential for future application as a cell scaffold in skin tissue engineering and wound healing.
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Implantes Absorbibles , Fibroblastos/efectos de los fármacos , Hidrogeles/síntesis química , Poliésteres/síntesis química , Polietilenglicoles/síntesis química , Resinas Acrílicas/química , Biomarcadores/metabolismo , Línea Celular , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Colágeno Tipo I/agonistas , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Cadena alfa 1 del Colágeno Tipo I , Colágeno Tipo III/agonistas , Colágeno Tipo III/genética , Colágeno Tipo III/metabolismo , Fibroblastos/citología , Fibroblastos/metabolismo , Expresión Génica/efectos de los fármacos , Humanos , Hidrogeles/farmacología , Poliésteres/farmacología , Polietilenglicoles/farmacología , Porosidad , ARN Mensajero/agonistas , ARN Mensajero/genética , ARN Mensajero/metabolismo , Piel/citología , Temperatura , Ingeniería de Tejidos/métodos , Cicatrización de Heridas/efectos de los fármacosRESUMEN
Aggregation-induced emission (AIE) is a unique phenomenon observed in various materials such as organic luminophores, carbon dots (CDs), organic-inorganic nanocomposites, fluorescent dye molecules, and nanoparticles (NPs). These AIE-active materials, or AIEgens, are ideal for balancing multifunctional phototheranostics and energy dissipation. AIE properties can manifest in organic fluorescent probes, rendering them effective for cancer treatment due to their ability to penetrate deeply and provide high therapeutic efficacy. This efficacy is attributed to their high photobleaching thresholds, ability to induce Stokes shifts, and capacity to activate fluorophores. Therefore, the development of innovative AIE-based materials for disease diagnosis and treatment, particularly for cancer, is both important and promising. Recent years have seen successful demonstrations of nanoparticles with AIE properties being used for photodynamic therapy (PDT) and multimodal imaging of tumor cells. These fluorophores have been shown to impact mitochondria and lysosomes, generate reactive oxygen species (ROS), activate the immune system, load and release drugs, and ultimately induce apoptosis in tumor cells. In this review, we examine previous studies on the manufacturing methods and effects of AIEgens on cancer cells, with a theranostic strategy of simultaneous treatment and imaging. We also investigate the factors affecting drug delivery on different cancer cells, including internal stimuli such as pH, ROS, enzymes, and external stimuli like near-infrared (NIR) light and ultrasound waves.
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Colorantes Fluorescentes , Nanopartículas , Neoplasias , Fotoquimioterapia , Nanomedicina Teranóstica , Humanos , Neoplasias/tratamiento farmacológico , Neoplasias/diagnóstico por imagen , Neoplasias/terapia , Nanomedicina Teranóstica/métodos , Animales , Nanopartículas/química , Fotoquimioterapia/métodos , Colorantes Fluorescentes/química , Colorantes Fluorescentes/administración & dosificación , Antineoplásicos/administración & dosificación , Antineoplásicos/uso terapéuticoRESUMEN
Electrospun nanofibrous membranes, with their unique structural features, can potentially enhance wound healing through controlled delivery of active agents. Here, an innovative porous nanofibrous membrane was developed as a dressing patch with antibacterial and anti-inflammatory functionalities for cutaneous wound healing. Zinc oxide nanoparticles (ZnO NPs) and Salvia abrotanoides essential oil (SAEO) were incorporated into sodium alginate, which served as the shell. Poly(ε-caprolactone) was used as the core of coaxial electrospun wound dressing nanofibers (PCL/SA@ZnO/SAEO). With the addition of ZnO NPs and SAEO, the average diameter of nanofibers was 187 ± 51 nm, with improved tensile strength (4.7 ± 0.4 MPa), elongation at break (32.9 ± 2.1), and elastic modulus (21.4 ± 2.0). Concurrent application of ZnO NPs and SAEO increased antimicrobial activity against Staphylococcus aureus and Escherichia coli and promoted the proliferation, attachment, and viability (>90 %) of L929 cells. The PCL/SA@ZnO/SAEO scaffold accelerated the healing time with total wound healing over 14 days in mouse models carrying full-thickness wounds compared to the nanofibrous scaffold without additives. Histopathological examinations demonstrated better tissue regeneration, i.e., enhanced collagen deposition, improved re-epithelialization, and neovascularization, and increased quantity of hair follicles. Moreover, the chicken chorioallantoic membrane assay confirmed the synergistic angiogenic effects of SAEO and ZnO NPs. Finally, the in vitro and in vivo results proposed the bioactive core-shell nanofibers synthesized as encouraging wound dressing materials for hastening the healing of cutaneous wounds.
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Alginatos , Nanofibras , Aceites Volátiles , Poliésteres , Salvia , Cicatrización de Heridas , Óxido de Zinc , Óxido de Zinc/química , Óxido de Zinc/farmacología , Cicatrización de Heridas/efectos de los fármacos , Nanofibras/química , Alginatos/química , Alginatos/farmacología , Animales , Salvia/química , Aceites Volátiles/farmacología , Aceites Volátiles/química , Ratones , Poliésteres/química , Staphylococcus aureus/efectos de los fármacos , Antibacterianos/farmacología , Antibacterianos/química , Nanopartículas/química , Línea Celular , Escherichia coli/efectos de los fármacos , VendajesRESUMEN
AIM: Silk fibroin/chitosan/ZnO/Astragalus arbusculinus (Ast) gum fibrous scaffolds along with adipose-derived mesenchymal stem cells (ADSCs) were investigated for accelerating diabetic wound healing. METHODS: Scaffolds with a core-shell structure and different compositions were synthesized using the electrospinning method. Biological in vitro investigations included antibacterial testing, cell viability analysis and cell attachment evaluation. In vivo experiments, including the chicken chorioallantoic membrane (CAM) test, were conducted to assess wound-healing efficacy and histopathological changes. RESULTS: The incorporation of Ast to the silk fibroin@ chitosan/ZnO scaffold improved wound healing in diabetic mice. In addition, seeding of ADSCs on the scaffold accelerated wound healing. CONCLUSION: These findings suggest that the designed scaffold can be useful for skin regeneration applications.
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Quitosano , Fibroínas , Células Madre Mesenquimatosas , Nanofibras , Andamios del Tejido , Cicatrización de Heridas , Óxido de Zinc , Quitosano/química , Animales , Cicatrización de Heridas/efectos de los fármacos , Fibroínas/química , Fibroínas/farmacología , Nanofibras/química , Ratones , Óxido de Zinc/química , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/efectos de los fármacos , Andamios del Tejido/química , Supervivencia Celular/efectos de los fármacos , Antibacterianos/farmacología , Antibacterianos/química , Humanos , Diabetes Mellitus Experimental , Membrana Corioalantoides/efectos de los fármacos , PollosRESUMEN
AIMS: Sustained-release systems reduce the incidence of drug side effects and the need for frequent drug consumption, thus increasing patient compliance with treatment. In this study, we aimed to produce sustained-release buprenorphine (BP) using lipid-liquid crystal gels. MAIN METHODS: The three experimental groups in this study included: group I: lipid-liquid crystal formulation 5 (F5) containing BP, group II: BP-free F5, group III: BP solution in NMP, and group IV: control (no treatment). The formulations were injected subcutaneously into the rabbits' back neck. KEY FINDINGS: The results showed that the time required to reach the drug's maximum concentration (Tmax) was longer in group I than in group III. The maximum BP concentration (Cmax) and the constants of the drug removal rate and drug absorption rate (Ka) were significantly higher in group III compared to group I. The half-life (t1/2) of the drug in blood circulation was significantly longer in group I than in group III. Histopathological analysis revealed no histological abnormalities in the skin and heart in group I (BP-containing F5); however, mild hyperemia was observed in interstitial vessels in group III (BP-containing NMP). The kidney and liver tissues showed normal structure in the control group, as well as groups I and II. However, in the group receiving BP-containing NMP, significant congestion, tissue damage, necrosis, and fibrosis were observed in the kidney and liver. SIGNIFICANCE: The results showed that the lipid-liquid crystal system can be used to design slow-release platforms for BP, minimizing the side effects associated with the use of its conventional forms.
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Buprenorfina , Cristales Líquidos , Animales , Conejos , Preparaciones de Acción Retardada/química , Lípidos , Geles/químicaRESUMEN
The microbiome in the female reproductive tract plays an essential role in immune modulation and reproductive health. However, various microbes become established during pregnancy, the balance of which plays a crucial role in embryonic development and healthy births. The contribution of disturbances in the microbiome profile to embryo health is poorly understood. A better understanding of the relationship between reproductive outcomes and the vaginal microbiota is needed to optimize the chances of healthy births. In this regards, microbiome dysbiosis refers to conditions in which the pathways of communication and balance within the normal microbiome are imbalanced due to the intrusion of pathogenic microorganisms into the reproductive system. This review summarizes the current state of knowledge on the natural human microbiome, with a focus on the natural uterine microbiome, mother-to-child transmission, dysbiosis, and the pattern of microbial change in pregnancy and parturition, and reviews the effects of artificial uterus probiotics during pregnancy. These effects can be studied in the sterile environment of an artificial uterus, and microbes with potential probiotic activity can be studied as a possible therapeutic approach. The artificial uterus is a technological device or biobag used as an incubator, allowing extracorporeal pregnancy. Establishing beneficial microbial communities within the artificial womb using probiotic species could modulate the immune system of both the fetus and the mother. The artificial womb could be used to select the best strains of probiotic species to fight infection with specific pathogens. Questions about the interactions and stability of the most appropriate probiotics, as well as dosage and duration of treatment, need to be answered before probiotics can be a clinical treatment in human pregnancy.
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Disbiosis , Microbiota , Embarazo , Femenino , Humanos , Transmisión Vertical de Enfermedad Infecciosa , Útero , VaginaRESUMEN
Rising to the challenge of formidable multi-step reaction needed for the synthesis of polycyclic compounds, an efficient one-pot two-step procedure for the synthesis of densely functionalized novel pyrazolo[5â³,1'':2',3']pyrimido[4',5':5,6] [1,4]thiazino[2,3-b]quinoxalines from synthetically accessible starting materials 6-bromo-7-chloro-3-cyano-2-(ethylthio)-5-methylpyrazolo[1,5-a]pyrimidine, 3-aminoquinoxaline-2-thiol and some readily accessible alkyl halides was established. The domino reaction pathway involves cyclocondensation/N-alkylation sequence in K2CO3/N,N-dimethyl formamide under heating condition. DPPH free radical scavenging activity of all synthesized pyrazolo[5â³,1'':2',3']pyrimido[4',5':5,6][1,4]thiazino[2,3-b]quinoxalines was evaluated to determine their antioxidant potentials. IC50 values were recorded in the range of 29-71 µM. N-benzyl substituted derivative represented the most effective antioxidant activity as well as antiproliferative activity against MCF-7 cells. Moreover, fluorescence in solution for these compounds exhibited strong red emission in the visible region (λflu. = 536-558 nm) with good to excellent quantum yields (61-95%). Due to their interesting fluorescence properties, these novel pentacyclic fluorophores can be used as fluorescent markers and probes for studies in biochemistry and pharmacology.
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BACKGROUND: In the recent decade, there has been increasing interest in preventing ovarian toxicity after chemotherapy exposure. It has been documented that ginger (Zingiber officinale) might normalize the hormonal balance and control the menstrual cycle.. OBJECTIVE: This study has analyzed whether ginger extract protects against cyclophosphamide (CP)-induced ovarian failure in rats. METHODS: Rats were distributed into four groups consisting of vehicle, CP, ginger, and CP + ginger. At the end of the treatment, all rats were killed under anesthesia to obtain ovarian tissues and blood samples for histological, molecular, and biochemical experiments. RESULTS: Our results indicated that ginger improves CP-caused histological changes in ovarian tissues and significantly restores serum hormonal abnormalities. Ginger also showed unique antioxidant, anti-inflammatory, and antiapoptotic properties in the ovarian tissues of CP-induced rats. Further, our findings indicated that ginger might activate the Nrf2 and SIRT and inhibit the PI3K/AKT pathway in the ovaries of CP-treated rats. In conclusion, ginger was found to protect against CP-caused ovarian toxicity in rats. CONCLUSION: The protective impacts of ginger may mediate, at least partly, by alleviating the oxidant state, inhibiting pro-inflammatory conditions, and exhibiting antiapoptotic activities.
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Antioxidantes , Zingiber officinale , Femenino , Ratas , Animales , Antioxidantes/farmacología , Ovario , Zingiber officinale/química , Fosfatidilinositol 3-Quinasas , Ciclofosfamida/toxicidadRESUMEN
In this study, the Supercritical Carbon Dioxide (scCO2) gas foaming procedure was used in the preparation of scaffolds containing the model drug dexamethasone (DXMT). The method used did not include an organic solvent thus making it a safe method. The ring-opening polymerization of PCL-PEG-PCL (PCEC) triblock was conducted using an organocatalyst [1,8 diazabicyclo [5.4.0] undec-7-ene (DBU)]. After mixing 5.0 g of DXMT with 50.0 g of PCEC, hydraulic pressure was applied to compress the mixed powder into disc-like tablets. The tablet-like scaffold of the triblock containing DXMT was inserted into a scCO2 gas-foaming device. The peak porosity percentage of the synthesized triblock was found to be 55.58 %. Pressure, temperature, soaking time and the time required to depressurize were recorded as 198 bar, 50 °C, 2.0 h, and 28 min respectively. After treatment with scCO2, the scaffolds experienced an almost full release of DXMT in vitro after 30 days (83.74 ± 1.54 % vs 52.24 ± 2.03 % before scCO2 treatment). In conclusion, the results proved that the scCO2 gas foaming procedure could be employed for constructing modifiable PCEC scaffolds with plausible porosity and structural and morphological features which can manipulate drug release.
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Dióxido de Carbono , Andamios del Tejido , Andamios del Tejido/química , Dióxido de Carbono/química , Porosidad , Polietilenglicoles/química , Poliésteres/química , Ingeniería de Tejidos/métodosRESUMEN
Aims: Achieving an effective biocompatible system for siRNAs delivery to the tumor site remains a significant challenge. Materials & methods: Selenium nanoparticles (SeNPs) modified by chitosan (CS) and hyaluronic acid (HA) were fabricated for PLK1 siRNAs (siPLK1) delivery to the bladder cancer cells. The HA-CS-SeNP@siPLK1 efficacy was evaluated using in vitro and in vivo models. Results: HA-CS-SeNP@siPLK1 was selectively internalized into T24 cells through clathrin-mediated endocytosis. Treatment with HA-CS-SeNP@siPLK1 successfully silenced the PLK1 gene, inhibited cell proliferation and induced cell cycle arrest in vitro. HA-CS-SeNP@siPLK1 could also inhibit tumor growth in vivo without causing systemic toxicity. Conclusion: Our results suggest that HA-CS-SeNPs may provide a good vehicle for delivering siPLK1 to the bladder tumor site.
siRNAs are small biomolecules shown as novel insights in cancer gene therapy because of their capability to silence target genes. However, achieving an effective biocompatible system for siRNA delivery to the tumor site remains a significant challenge. This work aimed to develop a nanoparticle-based delivery system consisting of selenium nanoparticles modified by chitosan and hyaluronic acid to sustain the release of siRNAs to bladder cancer cells. The results of this study demonstrated that this nanosystem successfully silenced the PLK1 gene and reduced the proliferation in vitro and in vivo. These findings suggest that hyaluronic acid-chitosan-selenium nanoparticles may open a new insight for targeted gene therapy for bladder cancer.
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Quitosano , Nanopartículas , Selenio , Neoplasias de la Vejiga Urinaria , Humanos , ARN Interferente Pequeño/genética , Ácido Hialurónico , Línea Celular Tumoral , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/terapia , Receptores de Hialuranos/genética , Receptores de Hialuranos/metabolismoRESUMEN
MicroRNAs (miRNAs) are small single-stranded regulatory RNAs that are shown to be dysregulated in a wide array of human cancers. MiRNAs play critical roles in cancer progression and function as either oncogenes or tumor suppressors through modulating various target genes. Therefore, they possess great potential as diagnostic and therapeutic targets for cancer detection and treatment. In particular, recent studies have illustrated that miR-425 is also dysregulated in various human malignancies and plays a fundamental role in cancer initiation and progression. miR-425 has been reported to function as a dual-role miRNA participating in the regulation of cellular processes, including metastasis, invasion, and cell proliferation by modulating multiple signaling pathways, such as TGF-ß, Wnt, and P13K/AKT pathways. Therefore, regarding recent researches showing the high therapeutic potential of miR-425, in this review, we have noted the impact of its dysregulation on signaling pathways and various aspects of tumorigenesis in a variety of human cancers.
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In this research the effect of sawdust, malt extract, and wheat bran on yield, biological efficiency (BE), and mycelia growth of Ganoderma lucidum was investigated. Three kinds of sawdust (beech, poplar, and hornbeam) as basal medium were mixed with two levels of wheat bran (5% and 10% w/w) and malt extract (2.5% and 5% w/w) as medium supplement for production of G. lucidum in factorial experiments on the basis of completely randomized design with three replications. The results showed that various kinds of sawdust affect fruiting body yield, BE, and mycelia growth rate significantly. The highest fruiting body yield and BE (102.58 g/kg and 12.89%, respectively) were found using hornbeam sawdust. The beech sawdust promotes the mycelia growth rate more than other sawdust. Analysis of variance showed that there is a significant interaction between the sawdust type and wheat bran, sawdust type and malt extract, and wheat bran and malt extract as far as yield and BE of G. lucidum was concerned. A final comparison of the different formulae indicated that the best combinations for high yield (142.44 g/kg) and BE (18.68%) were obtained in a combination of poplar sawdust with 5% malt extract and 10% wheat bran. The highest mycelia growth rate (10.6 mm/day) was obtained in a combination of beech sawdust with 2.5% malt extract and 10% wheat bran.
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Medios de Cultivo/química , Reishi/crecimiento & desarrollo , Residuos , Fibras de la Dieta/análisis , Cuerpos Fructíferos de los Hongos/crecimiento & desarrollo , Residuos Industriales , Madera/químicaRESUMEN
Cysteine is an essential biothiol that plays various functions in the human body. Decrease or exceeding of this excellent antioxidant from the expected range will lead to so many problems. Thus, appropriate sensing of it would be of great importance. Sulfur-doped carbon Dots(S-CDs) owe excellent fluorescence emission. Therefore, designing a Fluorescence resonance energy transfer (FRET) system between S-CDs as donor and Au nanoparticles (AuNPs) decorated tungsten disulfide nanosheet (WS2 NSs) would be a perfect strategy for cysteine detection. Excitation at 340 nm will give the maximum quantum yield of S-CDs (21%) and fluorescence emission peak at 460 nm. In the presence of cysteine, the FRET mechanism inhibited through the affinity of cysteine's functional groups (-SH and -NH2) toward AuNPs and S-CDs fluorescence emission was recovered. To find the best efficiency of the system, optimization of pH, temperature, and time was investigated. Here the linear range of 3-275 µM and limit of detection of 0.01 µM was obtained. Finally, the fluorescence method was applied to the analysis of cysteine in human blood serum, which poses the potential of rapid and sensitive sensing. It can detect both lower and higher amounts of serum cysteine.