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Osteoporosis is a systemic bone disease, which leads to decreased bone mass and an increased risk of fragility fractures. Currently, there are many anti-resorption drugs and osteosynthesis drugs, which are effective in the treatment of osteoporosis, but their usage is limited due to their contraindications and side effects. In regenerative medicine, the unique repair ability of mesenchymal stem cells (MSCs) has been favored by researchers. The exosomes secreted by MSCs have signal transduction and molecular delivery mechanisms, which may have therapeutic effects. In this review, we describe the regulatory effects of MSCs-derived exosomes on osteoclasts, osteoblasts, and bone immunity. We aim to summarize the preclinical studies of exosome therapy in osteoporosis. Furthermore, we speculate that exosome therapy can be a future direction to improve bone health.
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Excess myocardial triacylglycerol accumulation (i.e., cardiac steatosis) impairs heart function, suggesting that enzymes promoting triacylglycerol metabolism exert essential regulatory effects on heart function. Comparative gene identification 58 (CGI-58) is a key enzyme that promotes the hydrolysis of triglycerides by activating adipose triglyceride lipase and plays a protective role in maintaining heart function. In this study, the effects of CGI-58 on heart function and the underlying mechanism were investigated using cardiac-specific CGI58-knockout mice (CGI-58cko mice). Echocardiography and pathological staining were performed to detect changes in the structure and function of the heart. Proteomic profiling, immunofluorescent staining, western blotting, and real-time PCR were used to evaluate molecular changes. In CGI-58cko mice, we detected cardiac hypertrophic remodeling and heart failure associated with excessive cardiac lipid accumulation, ROS production, and decreased expression of regulators of fatty acid metabolism. These changes were markedly attenuated in CGI-58cko mice injected with rAAV9-CGI58. A quantitative proteomics analysis revealed significant increases in the expression of ER stress-related proteins and decreases in proteins related to fatty acid and amino acid metabolism in the hearts of CGI-58cko mice. Furthermore, the inhibition of ER stress by the inhibitor 4-PBA improved mitochondrial dysfunction, reduced oxidative stress, and reversed cardiac remodeling and dysfunction in cultured cardiomyocytes or in CGI-58cko mice. Our results suggested that CGI-58 is essential for the maintenance of heart function by reducing lipid accumulation and ER stress in cardiomyocytes, providing a new therapeutic target for cardiac steatosis and dysfunction.
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1-Acilglicerol-3-Fosfato O-Aciltransferasa/deficiencia , Estrés del Retículo Endoplásmico/genética , Insuficiencia Cardíaca/genética , Miocitos Cardíacos/metabolismo , Animales , Insuficiencia Cardíaca/mortalidad , Insuficiencia Cardíaca/fisiopatología , Masculino , Ratones , Análisis de SupervivenciaRESUMEN
BACKGROUND: Floating elbow along with ipsilateral multiple segmental forearm fracture is a rare and high-energy injury, although elbow dislocation or fracture of the ulna and radius may occur separately. CASE SUMMARY: We report the case of a 37-year-old woman with open (IIIA) fracture of the right distal humerus with multiple shaft fractures of the ipsilateral radius and ulna with a history of falling from a height of almost 20 m from a balcony. After providing advanced trauma life support, damage control surgery was performed to debride the arm wound and temporarily stabilize the right upper limb with external fixators in the emergency operating room. Subsequently, one-stage internal fixation of multiple fractures was performed with normal values of biochemical indicators and reduction in limb swelling. The patient achieved good outcome at the 7 mo follow-up. CONCLUSION: One- or two-stage treatment must be performed according to the type of injury; we efficiently used the "damage control principle."
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BACKGROUND: Fat embolism syndrome (FES) is a rare disease characterized by pulmonary distress, neurologic symptoms, and petechial rash and seriously threatens human life and health. It is still neglected clinically because of the lack of verifiable diagnostic criteria and atypical clinical symptoms. No studies on FES with pulmonary embolism (PE) and tympanic membrane perforation have been reported to date. Here, we report a rare case of concomitant FES, PE and tympanic membrane perforation after surgery in a patient with a tibiofibular fracture. CASE SUMMARY: A 39-year-old man presented with right lower extremity pain due to a car accident while driving a motorbike on the road. X-ray and computed tomography scans revealed a fracture of the right mid-shaft tibia and proximal fibula categorized as a type A2 fracture according to the AO classification. A successful minimally invasive operation was performed 3 d after the injury. Postoperatively, the patient developed sudden symptoms of respiratory distress and hearing loss. Early diagnosis was made, and supportive treatments were used at the early stage of FES. Seven days after surgery, he presented a clear recovery from respiratory symptoms. The outcome of fracture healing was excellent, and his hearing of the left ear was mildly impaired at the last follow-up of 4 mo. CONCLUSION: Concomitant FES, PE and tympanic membrane perforation are very rare but represent potentially fatal complications of trauma or orthopedic surgery and present with predominantly pulmonary symptoms. Early diagnosis and treatment can reduce the mortality of FES, and prevention is better than a cure.
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In this Letter, we proposed a super sensitive optic-fiber curvature sensor with ultra-low temperature crosstalk based on Vernier effect and achieved it experimentally. This sensor composes a pair of parallelized 2CFMIs (2-core-fiber Michelson interferometers) in similar lengths, both of which are involved sensing, but there is a rotation angle between their cross-sections. When the rotation angle approaches 180°, the magnification factor for curvature sensitivity is doubled compared with conventional Vernier effect, while for temperature it is always 1. Therefore, advanced curvature sensitivity and abated temperature crosstalk can be realized simultaneously when demodulating Vernier envelops. The experiment results indicate that the curvature sensitivity of this sensor reached 214.533nm/m-1, and temperature crosstalk was as low as 0.000276m-1/∘C. The fabrication process is extremely flexible and repeatable, and the magnification factor of Vernier effect could be controlled conveniently.
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OBJECTIVE: To analyze the effect of microRNA-22 on autophagy and proliferation and to investigate the underlying molecular mechanism of osteosarcoma cell chemotherapy sensitivity. METHODS: MG-63 cells were divided into four groups, including a control group, a negative control (NC) group, a cisplatin group, and a cisplatin + miR-22 group. Proliferation of MG-63 cells that had been treated with cisplatin and transfected with miR-22 mimics was determined using MTT assay and colony formation assay. We assessed the degree of autophagy using flow cytometry through cellular staining of the autophagy lysosomal marker monodansylcadaverine (MDC). The effect of microRNA-22 on autophagy was observed along with the expression levels of Beclin1, LC3, metadherin (MTDH) and ATG5 by western blot and quantitative reverse transcription polymerase chain reaction (qRT-PCR). Luciferase reporter assay revealed the targeted binding site between miR-22 and the 3'-untranslated region (3'-UTR) of MTDH mRNA. Western blot and qRT-PCR were used to explore the level of MTDH in the control group, the NC group, the cisplatin group, and the miR-22 group for 6, 12, and 24 h. RESULTS: In the in vitro study, the MTT results indicated that the MG-63 cells with overexpression of miR-22 exhibited a significant decline in the proliferation capacity compared with the control group (0.513 ± 0.001, P < 0.0005). Similar to the MTT results, MG-63 cells that were transfected with miR-22 mimic (101.0 ± 10.58) formed fewer colonies compared with the cisplatin group (129.7 ± 4.163). MDC staining revealed that miR-22-overexpressing osteosarcoma (OS) cells treated with cisplatin showed a significant decrease in the expression of autophagy (7.747 ± 0.117, P < 0.0001). Our data revealed that miR-22 could regulate not only autophagy but also proliferation in the chemosensitivity of osteosarcoma cells. We found that miR-22 sensitized osteosarcoma cells to cisplatin treatment by regulating autophagy-related genes. In addition, Luciferase Reporter Assay revealed that miR-22 negatively regulated autophagy through direct targeting of MTDH. We performed western blot analysis to detect the MTDH expression level. The results revealed that the overexpression of miR-22 obviously decreased the expression of MTDH (1.081 ± 0.023, P < 0.001). CONCLUSION: Inhibition of miR-22 ameliorated the anticancer drug-induced cell proliferation decrease in osteosarcoma cells. MTDH was identified as the miR-22 target in OS cells and MTDH-triggered autophagy played a key function in the miR-22-associated chemotherapy sensitivity.
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Autofagia/efectos de los fármacos , Neoplasias Óseas/tratamiento farmacológico , Proliferación Celular/efectos de los fármacos , Proteínas de la Membrana/farmacología , MicroARNs/farmacología , Osteosarcoma/tratamiento farmacológico , Proteínas de Unión al ARN/farmacología , Antineoplásicos/farmacología , Western Blotting , Neoplasias Óseas/ultraestructura , Cisplatino/farmacología , Citometría de Flujo , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Microscopía Electrónica de Transmisión , Osteosarcoma/ultraestructura , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
This paper proposes the potential extension of Ensemble Empirical Mode Decomposition based Causal Decomposition (EEMD-CD) to the physiological system. The neural basis of Volitional Motor Control (VMC), resulting in skilled motor behaviors through a connected interaction between limb biomechanical properties and Central Neural System (CNS), has been well documented. Specifically, the Primary Motor Cortex (M1) contributes volitional and goal-directed limb movements in terms of motor planning and motor behavior. The actual applications of causality detection approaches were still dominated by the prediction concept, i.e., Granger Causality (GC). This study concerns clearly some of components of M1 regulating motor properties of upper limbs, and holds the neuroscience finding from which the bi-directional causal interaction in brain and muscles has been concluded. The study performs an experiment by which Electromyography (EMG) of limb muscles and Electroencephalography (EEG) across from prefrontal cortex to M1, were synchronously acquired during wrist extensions. It also provides a valid example of how the casuality can be approached by EEMD-CD and offers a first step in the identification of casual relationship in mutual physiological systems.
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Corteza Motora/fisiología , Movimiento , Músculo Esquelético/fisiología , Procesamiento de Señales Asistido por Computador , Electroencefalografía , Electromiografía , Humanos , Extremidad Superior , MuñecaRESUMEN
MicroRNAs (miRNAs or miRs) play important roles in numerous cellular processes, including development, proliferation, tumorigenesis and apoptosis. It has been reported that miRNA expression is induced by ionizing radiation (IR) in cancer cells. However, the underlying molecular mechanisms are not yet fully understood. In this study, endogenous miR320a and its primary precursor (primiR320a) were assayed by reverse transcriptionquantitative PCR (RTqPCR). Luciferase activities were measured using a dualluciferase reporter assay system. Western blot analysis was used to determine the protein expressions of upstream and downstream genes of miR320a. Cell apoptosis was evaluated by Annexin V apoptosis assay and cell proliferation was measured using the trypan blue exclusion method. The results revealed that miR320a expression increased linearly with the IR dose and treatment duration. Three transcription factors, activating transcription factor 2 (ATF2), ETS transcription factor (ELK1) and YY1 transcription factor (YY1), were activated by p38 mitogenactivated protein kinase (MAPK) and mitogenactivated protein kinase 8 (JNK) and by upregulated miR320a expression under IR conditions. In addition, it was identified that Xlinked inhibitor of apoptosis (XIAP) was an miR320a target gene during the IR response. By targeting XIAP, miR320a induced apoptosis and inhibited the proliferation of the cancer cells. On the whole, the results of this study demonstrated that miRNA320a, regulated by the p38 MAPK/JNK pathway, enhanced the radiosensitivity of cancer cells by inhibiting XIAP and this may thus prove to be a potential therapeutic approach with which to overcome radioresistance in cancer treatment.
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Apoptosis/efectos de la radiación , Sistema de Señalización de MAP Quinasas/efectos de la radiación , MicroARNs/genética , Neoplasias/radioterapia , Proteína Inhibidora de la Apoptosis Ligada a X/genética , Factor de Transcripción Activador 2/genética , Factor de Transcripción Activador 2/metabolismo , Apoptosis/genética , Línea Celular Tumoral , Proliferación Celular/genética , Proliferación Celular/efectos de la radiación , Relación Dosis-Respuesta en la Radiación , Regulación Neoplásica de la Expresión Génica/efectos de la radiación , Humanos , Sistema de Señalización de MAP Quinasas/genética , MicroARNs/metabolismo , Neoplasias/genética , Regiones Promotoras Genéticas , ARN Interferente Pequeño/metabolismo , Tolerancia a Radiación/genética , Radiación Ionizante , Resultado del Tratamiento , Regulación hacia Arriba/efectos de la radiación , Proteína Inhibidora de la Apoptosis Ligada a X/metabolismo , Factor de Transcripción YY1/genética , Factor de Transcripción YY1/metabolismo , Proteína Elk-1 con Dominio ets/genética , Proteína Elk-1 con Dominio ets/metabolismoRESUMEN
ß-Defensins are small antimicrobial proteins expressed in various organisms and have great potential for improving animal health and selective breeding programs. Giant pandas have a distinctive lineage in Carnivora, and it is unclear whether ß-defensin genes have experienced different selective pressures during giant panda evolution. We therefore characterized the giant panda (Ailuropoda melanoleuca) ß-defensin gene family through gap filling, TBLASTN, and HMM searches. Among 36 ß-defensins identified, gastrointestinal disease may induce the expression of the DEFB1 and DEFB139 genes in the digestive system. Moreover, for DEFB139, a significant positive selection different from that of its homologs was revealed through branch model comparisons. A Pro-to-Arg mutation in the giant panda DEFB139 mature peptide may have enhanced the peptide's antimicrobial potency by increasing its stability, isoelectric point, surface charge and surface hydrophobicity, and by stabilizing its second ß-sheet. Broth microdilution tests showed that the increase in net charge caused by the Pro-to-Arg mutation has enhanced the peptide's potency against Staphylococcus aureus, although the increase was minor. We expect that additional gene function and expression studies of the giant panda DEFB139 gene could improve the existing conservation strategies for the giant panda.
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Antiinfecciosos/química , Ursidae/genética , beta-Defensinas/química , beta-Defensinas/genética , Secuencia de Aminoácidos , Animales , Punto Isoeléctrico , Mutación , FilogeniaRESUMEN
A novel bidirectional high-sensitivity fiber-optic bending sensor based on the concave-lens-like long-period fiber grating (CLL-LPFG) is designed and demonstrated. The CLL-LPFG is composed by an array of arc-shaped grating planes, and accordingly, its refractive index modulation serves as a concave lens. As a result, the eigencladding mode of the device gets closer to the device surface than the conventional counterpart. Therefore, the proposed sensor provides a more sensitive result. The experimental results show that the bending sensitivities of the CLL-LPFG reach -32.782 nm/m-1 within the bending range of 0-2.08 m-1, which is about sixfold compared to the reported arts. The sensitivity can be potentially improved by optimizing the grating parameters, and the temperature characteristics of the CLL-LPFG can be used to manipulate the grating spectrum.
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We demonstrate the fabrication of an angle-chirped long-period fiber grating (ACLPFG) in a single-mode fiber via CO2 laser pulses. Because of the Berry phase introduced by the ACLPFG, the interference acquires an extra phase difference determined by the torsion of the device. By using that unique characteristic of the proposed device, a high sensitivity sine function torsion response is achieved. The torsion sensitivity is significantly improved, and the temperature crosstalk is effectively avoided by using the relative measurement technology. The torsion sensitivity is ~16 folds (~0.94 nm/ (rad/m)) higher than that of the normal long-period fiber grating (LPFG) with only ~0.006 nm/°C temperature crosstalk within the range of 25-80 °C, which is ~10 folds lower than that of the normal LPFG.
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We fabricated a microfiber interferometer with surface plasmon-polaritons (SPPs) involvement. Commonly, the SPPs are not involved in interference due to the mismatch momentum and ultrashort propagation distance. In this Letter, an absorber-doped microfiber is utilized for increasing the matched momentum (i.e., their modal projection), and as a result, an SPP is coherent with an end-fire method-stimulated hybrid SPP. A mathematical model is proposed for investigating the modal-projection-caused interference, and its results show that the proposed interferometer is very dependent on the polarization. Confirmation experiments were carried out, and a good agreement between theoretical predictions and experimental results was found. The proposed interferometer will potentially facilitate many SPP studies in directly related fields.
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An in-line polarization rotator (PR) is proposed based on the quantum-optical analogy (QOA). The proposed PR possesses an auxiliary E7 liquid crystal (LC) waveguide in the vicinity of the single-mode fiber (SMF) core. Because of the matched core size, the PR demonstrates good compatibility with the established backbone networks which are composed of conventional SMFs. With optimized parameters for the auxiliary waveguide, the PR offers a near 100% polarization conversion efficiency at the 1550 nm band with a bandwidth of â¼30 nm, a length of â¼4625.9 µm with a large tolerance of â¼550 µm, and a tolerance of the input light polarization angle and rotation angle of the E7 LC of â¼π/30 and â¼π/36 rad, respectively. The performance was verified by the full-vector finite-element method. The proposed PR can be easily fabricated based on the existing photonics crystal fiber manufacturing process, making it a potentially inexpensive device for applications in modern communication systems. Moreover, the QOA, compared with the previous supermode-theory design method, allows a designer to consider several waveguides separately. Therefore, various unique characteristics can be met simultaneously which is consistent with the trend of modern fiber design.
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A novel refractive index (RI) sensor head is proposed and experimentally demonstrated in this paper. The proposed sensor head is composed of a segment of bared single-mode fiber and a fiber holder that is fabricated by a 3D printer. The mechanism of the sensor head is based on dual polarized Mach-Zehnder interference. According to the aforementioned mechanism, we derived that the RI responses of the resonance dips possess an exponential functional manner when the E field is along the fast or slow axes. In addition, based on the finite element method, we found that the resonance dips wavelength responses are more sensitive when the input E field is along the fast axis. A confirmation experiment was performed, and the results confirmed our hypothesis. The maximum arithmetic mean value of RI response is about 657.895 nm/RIU for the proposed sensor head when the ambient RI changes from 1.3350 to 1.4110. Moreover, in the case of the proposed liquid RI sensor head, aligning the E field along the fast axis is the potentially needed condition for polarization.
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Tecnología de Fibra Óptica/métodos , Interferometría/métodos , Fibras Ópticas , Refractometría , ElectricidadRESUMEN
Maternally Expressed Gene 3 (MEG3) encodes a lncRNA which is suggested to function as a tumor suppressor. Previous studies suggested that MEG3 functioned through activation of p53, however, the functional properties of MEG3 remain obscure and their relevance to human diseases is under continuous investigation. Here, we try to illuminate the relationship of MEG3 and p53, and the consequence in hepatoma cells. We find that transfection of expression construct of MEG3 enhances stability and transcriptional activity of p53. Deletion analysis of MEG3 confirms that full length and intact structure of MEG3 are critical for it to activate p53-mediated transactivation. Interestingly, our results demonstrate for the first time that MEG3 can interact with p53 DNA binding domain and various p53 target genes are deregulated after overexpression of MEG3 in hepatoma cells. Furthermore, results of qRT-PCR have shown that MEG3 RNA is lost or reduced in the majority of HCC samples compared with adjacent non-tumorous samples. Ectopic expression of MEG3 in hepatoma cells significantly inhibits proliferation and induces apoptosis. In conclusion, our data demonstrates that MEG3 functions as a tumor suppressor in hepatoma cells through interacting with p53 protein to activate p53-mediated transcriptional activity and influence the expression of partial p53 target genes.
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Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , ARN Largo no Codificante/genética , Proteína p53 Supresora de Tumor/genética , Apoptosis/genética , Línea Celular , Línea Celular Tumoral , Proliferación Celular/genética , Metilación de ADN/genética , Regulación Neoplásica de la Expresión Génica/genética , Genes Supresores de Tumor/fisiología , Células HCT116 , Células HEK293 , Células Hep G2 , Humanos , Datos de Secuencia Molecular , Regiones Promotoras Genéticas/genética , Activación Transcripcional/genéticaRESUMEN
Inkjet printing of drug nanosuspension on edible porous substrates was carried out for the first time with the objective of preparing personalized dosage forms of poorly soluble drugs. Amorphous drug-polysaccharide nanoparticle complex (or drug nanoplex in short) was used as the nanosuspension ink, instead of the conventional crystalline nanodrug. The amorphous drug nanoplex exhibited low propensity to Ostwald ripening growth, high colloidal stability, and supersaturation generation capability making it ideal for printing. Nanoplexes of ciprofloxacin - a BCS Class IV compound - prepared by complexation with dextran sulfate were used as the nanosuspension ink at two different sizes (i.e. ≈265nm and 188nm). Inkjet printing was performed on cellulose substrate at 0.25% (w/v) nanosuspension concentration and 5% (w/v) polyethylene glycol. For both nanoplex sizes, the results indicated that the printed dose could be increased by increasing the number of droplets dispensed. However, exact correlations between the achievable dose and the number of droplets dispensed were not evident, which was likely caused by the spatial non-homogeneity in the nanosuspension concentration. Compared to the larger nanoplex, printed nanodrugs of the smaller nanoplex consistently exhibited higher payload with better batch-to-batch reproducibility (<6%). The maximum achievable payload was equal to ≈2.5µg/cm(2), which was multifold higher than that achieved had inkjet printing of ciprofloxacin solution been performed. Nevertheless, print substrate with higher liquid uptake capacity is needed to increase the payload nearer to the therapeutic dose. Lastly, the drug release and non-cytotoxicity of the printed nanodrug were successfully established in vitro.
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Antibacterianos/química , Ciprofloxacina/química , Sulfato de Dextran/química , Excipientes/química , Derivados de la Hipromelosa/química , Nanopartículas/química , Medicina de Precisión , Antibacterianos/administración & dosificación , Antibacterianos/efectos adversos , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Ciprofloxacina/administración & dosificación , Ciprofloxacina/efectos adversos , Sulfato de Dextran/efectos adversos , Portadores de Fármacos/administración & dosificación , Portadores de Fármacos/efectos adversos , Portadores de Fármacos/química , Composición de Medicamentos , Liberación de Fármacos , Estabilidad de Medicamentos , Excipientes/efectos adversos , Humanos , Derivados de la Hipromelosa/efectos adversos , Nanopartículas/efectos adversos , Nanopartículas/ultraestructura , Tamaño de la Partícula , Poloxámero/efectos adversos , Poloxámero/química , Polietilenglicoles/efectos adversos , Polietilenglicoles/química , Impresión Tridimensional , Control de Calidad , Solubilidad , Propiedades de Superficie , ViscosidadRESUMEN
A photonic crystal fiber polarization rotator (PR) is proposed based on the topological Zeeman effect. The proposed PR is achieved by permanently twisting a segment of sixfold symmetric photonic crystal fiber with a matched length, and under the optimized parameters, the PR can offer an almost 100% polarization conversion ratio in the wavelength of 1.55-µm band (â¼200 nm bandwidth) and a compact length of about 157 µm based on the numerical simulation result of the full-vector finite-element method. The proposed in-line PCF PR can be easily fabricated based on state-of-art PCF manufacturing, and it is a potential inexpensive candidate in the application of modern communication systems.
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Long noncoding RNAs (lncRNAs) are nonprotein coding transcripts longer than 200 nucleotides. Recently in mammals, thousands of long noncoding RNAs have been identified and studied as key molecular players in different biological processes with protein complexes. As a long noncoding RNA, maternally expressed gene 3 (MEG3) plays an important role in many cellular processes. However, the mechanism underlying MEG3 regulatory effects remains enigmatic. By using the specific interaction between MS2 coat protein and MS2 RNA hairpin, we developed a method (MS2-tagged RNA affinity purification and mass spectrometry (MTRAP-MS)) to identify proteins that interact with MEG3. Mass spectrometry and gene ontology (GO) analysis showed that MEG3 binding proteins possess nucleotide binding properties and take part in transport, translation, and other biological processes. In addition, interleukin enhancer binding factor 3 (ILF3) and poly(A) binding protein, cytoplasmic 3 (PABPC3) were validated for their interaction with MEG3. These findings indicate that the newly developed method can effectively enrich lncRNA binding proteins and provides a strong basis for studying MEG3 functions.
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ARN Largo no Codificante/metabolismo , Proteínas de Unión al ARN/aislamiento & purificación , Proteínas de Unión al ARN/metabolismo , Células HEK293 , Humanos , Espectrometría de Masas , Proteínas del Factor Nuclear 90/química , Proteínas del Factor Nuclear 90/aislamiento & purificación , Proteínas del Factor Nuclear 90/metabolismo , Proteínas de Unión a Poli(A)/química , Proteínas de Unión a Poli(A)/aislamiento & purificación , Proteínas de Unión a Poli(A)/metabolismo , Proteínas de Unión al ARN/química , Especificidad por SustratoRESUMEN
While the wide-ranging therapeutic activities of curcumin have been well established, its successful delivery to realize its true therapeutic potentials faces a major challenge due to its low oral bioavailability. Even though nano-encapsulation has been widely demonstrated to be effective in enhancing the bioavailability of curcumin, it is not without drawbacks (i.e. low payload and costly preparation). Herein we present a cost-effective bioavailability enhancement strategy of curcumin in the form of amorphous curcumin-chitosan nanoparticle complex (or curcumin nanoplex in short) exhibiting a high payload (>80%). The curcumin nanoplex was prepared by a simple yet highly efficient drug-polysaccharide complexation method that required only mixing of the curcumin and chitosan solutions under ambient condition. The effects of (1) pH and (2) charge ratio of chitosan to curcumin on the (i) physical characteristics of the nanoplex (i.e. size, colloidal stability and payload), (ii) complexation efficiency, and (iii) production yield were investigated from which the optimal preparation condition was determined. The nanoplex formation was found to favor low acidic pH and charge ratio below unity. At the optimal condition (i.e. pH 4.4. and charge ratio=0.8), stable curcumin nanoplex (≈260nm) was prepared at >90% complexation efficiency and ≈50% production yield. The amorphous state stability, colloidal stability, and in vitro non-cytotoxicity of the nanoplex were successfully established. The curcumin nanoplex produced prolonged supersaturation (3h) in the presence of hydroxypropyl methylcellulose (HPMC) at five times of the saturation solubility of curcumin. In addition, curcumin released from the nanoplex exhibited improved chemical stability owed to the presence of chitosan. Both results (i.e. high supersaturation and improved chemical stability) bode well for the ability of the curcumin nanoplex to enhance the bioavailability of curcumin clinically.
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Quitosano/química , Curcumina/química , Portadores de Fármacos/química , Nanopartículas/química , Tecnología Farmacéutica/métodos , Disponibilidad Biológica , Biofarmacia , Cápsulas , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Curcumina/administración & dosificación , Curcumina/farmacocinética , Curcumina/farmacología , Composición de Medicamentos , Liberación de Fármacos , Estabilidad de Medicamentos , Células Epiteliales/efectos de los fármacos , Humanos , Microscopía Electrónica de Rastreo , Tamaño de la Partícula , Solubilidad , Propiedades de SuperficieRESUMEN
The giant panda Ailuropoda melanoleuca is an endangered species and is a symbol for wildlife conservation. Although efforts have been made to protect this rare and endangered species through breeding and conservative biology, the long-term preservation of giant panda genome resources (gametes, tissues, organs, genomic libraries, etc.) is still a practical option. In this study, the giant panda skeletal muscle-derived cell line was successfully established via primary explants culture and cryopreservation techniques. The population doubling time of giant panda skeletal cells was approximately 33.8 h, and this population maintained a high cell viability before and after cryopreservation (95.6% and 90.7%, respectively). The two skeletal muscle-specific genes SMYD1 and MYF6 were expressed and detected by RT-PCR in the giant panda skeletal muscle-derived cell line. Karyotyping analysis revealed that the frequencies of giant panda skeletal muscle cells showing a chromosome number of 2n=42 ranged from 90.6â¼94.2%. Thus, the giant panda skeletal muscle-derived cell line provides a vital resource and material platform for further studies and is likely to be useful for the protection of this rare and endangered species.