RESUMEN
The reduction of nitrobenzene to aniline is very important for both pollution control and chemical synthesis. Nevertheless, difficulties still remain in developing a catalytic system having high efficiency and selectivity for the production of aniline. Herein, it was found that PdO nanoparticles highly dispersed on TiO2 support (PdO/TiO2) functioned as a highly efficient catalyst for the reduction of nitrobenzene in the presence of NaBH4. Under favorable conditions, 95% of the added nitrobenzene (1 mmol/L) was reduced within 1 min with an ultra-low apparent activation energy of 10.8 kJ/mol by using 0.5%PdO/TiO2 as catalysts and 2 mmol/L of NaBH4 as reductants, and the selectivity to aniline even reached up to 98%. The active hydrogen species were perceived as dominant species during the hydrogenation of nitrobenzene by the results of isotope labeling experiments and ESR spectroscopic. A mechanism was proposed as follows: PdO activates the nitro groups and leads to in-situ generation of Pd, and the generated Pd acts as the reduction sites to produce active hydrogen species. In this catalytic system, nitrobenzene prefers to be adsorbed on the PdO nanoparticles of the PdO/TiO2 composite. Subsequently, the addition of NaBH4 results in in-situ generation of a Pd/PdO/TiO2 composite from the PdO/TiO2 composite, and the Pd nanoclusters would activate NaBH4 to generate active hydrogen species to attack the adsorbed nitro groups. This work will open up a new approach for the catalytic transfer hydrogenation of nitrobenzene to aniline in green chemistry.
Asunto(s)
Compuestos de Anilina , Nitrobencenos , Paladio , Titanio , Nitrobencenos/química , Compuestos de Anilina/química , Titanio/química , Hidrogenación , Catálisis , Paladio/química , Modelos QuímicosRESUMEN
This study investigated whether lower extremity stiffness plays a role in the enhancement of change of direction speed (CODS) and the duration of this enhancement after dynamic loaded warm-up (DLWU). Fifteen badminton athletes underwent DLWU, and CODS, individual muscle and tendon stiffness, and vertical stiffness were measured before DLWU and 6, 12, and 18 min after DLWU. The data were analyzed using ANOVA and covariance analysis. Significant improvements in CODS were found at 6, 12, and 18 min post-DLWU compared to pre-DLWU (p < 0.05). The Achilles tendon stiffness of the dominant leg increased at 6 min (p = 0.039) and 18 min (p = 0.024) post-DLWU compared to pre-DLWU. Achilles tendon stiffness of the dominant leg had a significant effect on improving CODS (p > 0.05). CODS improvement lasted up to 18 min after DLWU in badminton athletes, potentially related to increased Achilles tendon stiffness of the dominant leg.
RESUMEN
Production of amorphous solid dispersions (ASDs) is an effective strategy to promote the solubility and bioavailability of poorly water soluble medicinal substances. In general, ASD is manufactured using a variety of classic and modern techniques, most of which rely on either melting or solvent evaporation. This proof-of-concept study is the first ever to introduce electromagnetic drop-on-demand (DoD) technique as an alternative solvent evaporation-based method for producing ASDs. Herein 3D printing of ASDs for three drug-polymer combinations (efavirenz-Eudragit L100-55, lumefantrine-hydroxypropyl methylcellulose acetate succinate, and favipiravir-polyacrylic acid) was investigated to ascertain the reliability of this technique. Polarized light microscopy, differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), and Fourier Transform Infrared (FTIR) spectroscopy results supported the formation of ASDs for the three drugs by means of DoD 3D printing, which significantly increases the equilibrium solubility of efavirenz from 0.03 ± 0.04 µg/ml to 21.18 ± 4.20 µg/ml, and the equilibrium solubility of lumefantrine from 1.26 ± 1.60 µg/ml to 20.21 ± 6.91 µg/ml. Overall, the reported findings show how this new electromagnetic DoD technology can have a potential to become a cutting-edge 3D printing solvent-evaporation technique for on-demand and continuous manufacturing of ASDs for a variety of drugs.
Asunto(s)
Impresión Tridimensional , Solubilidad , Tecnología Farmacéutica/métodos , Composición de Medicamentos/métodos , Polímeros/química , Fenómenos Electromagnéticos , Prueba de Estudio Conceptual , Difracción de Rayos X , Química Farmacéutica/métodosRESUMEN
The functional alterations of proteins and nucleic acids mainly rely on their modifications. ADP-ribosylation is a NAD+-dependent modification of proteins and, in some cases, of nucleic acids. This modification is broadly categorized as Mono(ADP-ribosyl)ation (MARylation) or poly(ADP-ribosyl)ation (PARylation). MARylation catalyzed by mono(ADP-ribosyl) transferases (MARTs) is more common in cells and the number of MARTs is much larger than poly(ADP-ribosyl) transferases. Unlike PARylation is well-characterized, research on MARylation is at the starting stage. However, growing evidence demonstrate the cellular functions of MARylation, supporting its potential roles in human health and diseases. In this review, we outlined MARylation-associated proteins including MARTs, the ADP-ribosyl hydrolyses and ADP-ribose binding domains. We summarized up-to-date findings about MARylation onto newly identified substrates including protein, DNA and RNA, and focused on the functions of these reactions in pathophysiological conditions as well as speculated the potential mechanisms. Furthermore, new strategies of MARylation detection and the current state of MARTs inhibitors were discussed. We also provided an outlook for future study, aiming to revealing the unknown biological properties of MARylation and its relevant mechanisms, and establish a novel therapeutic perspective in human diseases.
RESUMEN
Three-dimensional (3D) printing is a promising approach for the stabilization and delivery of non-living biologics. This versatile tool builds complex structures and customized resolutions, and has significant potential in various industries, especially pharmaceutics and biopharmaceutics. Biologics have become increasingly prevalent in the field of medicine due to their diverse applications and benefits. Stability is the main attribute that must be achieved during the development of biologic formulations. 3D printing could help to stabilize biologics by entrapment, support binding, or crosslinking. Furthermore, gene fragments could be transited into cells during co-printing, when the pores on the membrane are enlarged. This review provides: (i) an introduction to 3D printing technologies and biologics, covering genetic elements, therapeutic proteins, antibodies, and bacteriophages; (ii) an overview of the applications of 3D printing of biologics, including regenerative medicine, gene therapy, and personalized treatments; (iii) information on how 3D printing could help to stabilize and deliver biologics; and (iv) discussion on regulations, challenges, and future directions, including microneedle vaccines, novel 3D printing technologies and artificial-intelligence-facilitated research and product development. Overall, the 3D printing of biologics holds great promise for enhancing human health by providing extended longevity and enhanced quality of life, making it an exciting area in the rapidly evolving field of biomedicine.
Asunto(s)
Productos Biológicos , Calidad de Vida , Humanos , Sistemas de Liberación de Medicamentos , Impresión Tridimensional , Medicina de PrecisiónRESUMEN
Recently, binder jet printed modular tablets were loaded with three anti-viral drugs via Drop on Demand (DoD) technology where drug solutions prepared in ethanol showed faster release than those prepared in water. During printing, water is used as a binding agent, whereas ethanol is added to maintain the porous structure of the tablets. Thus, the hypothesis is that the porosity would be controlled by manipulating the percentage of water and ethanol. In this study, Rhodamine 6G (R6G) was selected as a model drug due to its high solubility in water and ethanol, visualization function as a fluorescent dye, and potential therapeutic effects for cancer treatment. Approximately, 10 mg/ml R6G solutions were prepared with five different water-ethanol ratios (0-100, 75-25, 50-50, 75-25, 100-0). The ink solutions were printed onto blank binder jet 3D-printed tablets containing calcium sulphate hemihydrate using DoD technology. The tablets were dried at room temperature and then characterized using SEM-EDX, fluorescent microscope, TGA, XRD, FTIR, and DSC as well as in vitro release studies to investigate the impact of water-ethanol ratio on the release profile of R6G. Results indicated that the solution with higher ethanol ratio penetrated the tablets faster than the lower ethanol ratio, while the solution prepared with pure water was first accumulated onto the tablets' surface and then absorbed by the tablets. Moreover, tablets with more water content gained more weight and thickness. The EDX analysis and fluorescent microscope showed the uniform surface distribution of the drug. The SEM images revealed the difference in the tablet surface among the five formulations. Furthermore, the TGA data presents a notable increase in water loss, with XRD analysis suggesting the formation of gypsum in tablets containing elevated water content. The release study exhibited that the fastest release was from WE0-100, whereas the release rate decreases as the content of water increases. The WE0-100 releases more than 40 % drug within the first hour which is almost twice as high of the WE100-0 formulation. This DoD technology could distribute drugs onto the tablet's surface uniformly. The calcium sulfate would transform from hemihydrate to dihydrate form in the presence of water and therefore, those tablets treated with higher water content led to slower release. In conclusion, this study underscores the substantial impact of the water-ethanol ratio on drug release from binder jet printed tablets and highlights the potential of DoD technology for uniform drug distribution and controlled release.
Asunto(s)
Sulfato de Calcio , Tecnología Farmacéutica , Solventes , Tecnología Farmacéutica/métodos , Liberación de Fármacos , Agua , Comprimidos/química , Impresión Tridimensional , EtanolRESUMEN
Selective laser sintering (SLS) is a single-step, three-dimensional printing (3DP) process that is gaining momentum in the manufacturing of pharmaceutical dosage forms. It also offers opportunities for manufacturing various pharmaceutical dosage forms with a wide array of drug delivery systems. This research aimed to introduce carbonyl iron as a multifunctional magnetic and heat conductive ingredient for the fabrication of oral tablets containing isoniazid, a model antitubercular drug, via SLS 3DP process. Furthermore, the effects of magnetic iron particles on the drug release from the SLS printed tablets under a specially designed magnetic field was studied. Optimization of tablet quality was performed by adjusting SLS printing parameters. The independent factors studied were laser scanning speed, hatching space, and surface/chamber temperature. The responses measured were printed tablets' weight, hardness, disintegration time, and dissolution performance. It has been observed that, for the drug formulation with carbonyl iron, due to its inherent thermal conductivity, sintering tablets required relatively lower laser energy input to form the tablets of the same quality attributes as the other batches that contained no magnetic particles. Also, printed tablets with carbonyl iron released 25% more drugs under a magnetic field than those without it. It can be claimed that magnetic nanoparticles appear as an alternative conductive material to facilitate the sintering process during SLS 3DP of dosage forms.
Asunto(s)
Nanopartículas de Magnetita , Comprimidos , Sistemas de Liberación de Medicamentos/métodos , Impresión Tridimensional , Rayos LáserRESUMEN
Amorphous solid dispersion (ASD) is one of the most important strategies to improve the solubility and dissolution rate of poorly water-soluble drugs. As a widely used technique to prepare ASDs, hot-melt extrusion (HME) provides various benefits, including a solvent-free process, continuous manufacturing, and efficient mixing compared to solvent-based methods, such as spray drying. Energy input, consisting of thermal and specific mechanical energy, should be carefully controlled during the HME process to prevent chemical degradation and residual crystallinity. However, a conventional ASD development process uses a trial-and-error approach, which is laborious and time-consuming. In this study, we have successfully built multiple machine learning (ML) models to predict the amorphization of crystalline drug formulations and the chemical stability of subsequent ASDs prepared by the HME process. We utilized 760 formulations containing 49 active pharmaceutical ingredients (APIs) and multiple types of excipients. By evaluating the built ML models, we found that ECFP-LightGBM was the best model to predict amorphization with an accuracy of 92.8%. Furthermore, ECFP-XGBoost was the best in estimating chemical stability with an accuracy of 96.0%. In addition, the feature importance analyses based on SHapley Additive exPlanations (SHAP) and information gain (IG) revealed that several processing parameters and material attributes (i.e., drug loading, polymer ratio, drug's Extended-connectivity fingerprints (ECFP) fingerprints, and polymer's properties) are critical for achieving accurate predictions for the selected models. Moreover, important API's substructures related to amorphization and chemical stability were determined, and the results are largely consistent with the literature. In conclusion, we established the ML models to predict formation of chemically stable ASDs and identify the critical attributes during HME processing. Importantly, the developed ML methodology has the potential to facilitate the product development of ASDs manufactured by HME with a much reduced human workload.
RESUMEN
An umbrella review and meta-analysis were conducted to summarize evidence for the association between dietary factors and the incidence of osteoporosis in adults. Only systematic reviews or meta-analyses were eligible for this study. Two researchers independently performed reading, data extraction, and quality evaluation of the included literature. The outcomes included in this study were all associated with osteoporosis, including osteoporotic fractures and low bone density. A total of 54 studies were included in this study, with 83 adjusted hazard ratios on diet, dairy group (n = 13), alcohol (n = 2), tea (n = 6), coffee (n = 3), micronutrient (n = 31), dietary pattern (n = 21), and foods (n = 7) regarding the incidence of osteoporosis. Grades of Recommendations, Assessment, Development, and Evaluation (GRADE) quality assessment method was used in this study. The high, medium, low and very low quality studies accounted for 27.7, 41, 21.7 and 9.6% of this study, respectively. Based on the included literature studies in this umbrella review, it was found that dietary factors have a relevant impact on the incidences of human osteoporosis, appropriate consumption of dairy products, vegetables, fruits, and micronutrients, as well as reduced intake of alcohol and coffee, can reduce the risk of osteoporosis.
Asunto(s)
Café , Osteoporosis , Humanos , Dieta , Frutas , Estudios Observacionales como Asunto , Osteoporosis/epidemiología , VerdurasRESUMEN
Recently, various innovative technologies have been developed for the enhanced delivery of biologics as attractive formulation targets including polymeric micro and nanoparticles. Combined with personalized medicine, this area can offer a great opportunity for the improvement of therapeutics efficiency and the treatment outcome. Herein, a novel manufacturing method has been introduced to produce protein-loaded chitosan particles with controlled size. This method is based on an additive manufacturing technology that allows for the designing and production of personalized particulate based therapeutic formulations with a precise control over the shape, size, and potentially the geometry. Sprayed multi adsorbed-droplet reposing technology (SMART) consists of the high-pressure extrusion of an ink with a well determined composition using a pneumatic 3D bioprinting approach and flash freezing the extrudate at the printing bed, optionally followed by freeze drying. In the present study, we attempted to manufacture trypsin-loaded chitosan particles using SMART. The ink and products were thoroughly characterized by dynamic light scattering, rheometer, Scanning Electron Microscopy (SEM), and Fourier Transform Infra-Red (FTIR) and Circular Dichroism (CD) spectroscopy. These characterizations confirmed the shape morphology as well as the protein integrity over the process. Further, the effect of various factors on the production were investigated. Our results showed that the concentration of the carrier, chitosan, and the lyoprotectant concentration as well as the extrusion pressure have a significant effect on the particle size. According to CD spectra, SMART ensured Trypsin's secondary structure remained intact regardless of the ink composition and pressure. However, our study revealed that the presence of 5% (w/v) lyoprotectant is essential to maintain the trypsin's proteolytic activity. This study demonstrates, for the first time, the viability of SMART as a single-step efficient process to produce biologics-based stable formulations with a precise control over the particulate morphology which can further be expanded across numerous therapeutic modalities including vaccines and cell/gene therapies.
RESUMEN
3D printed drug delivery systems have gained tremendous attention in pharmaceutical research due to their inherent benefits over conventional systems, such as provisions for customized design and personalized dosing. The present study demonstrates a novel approach of drop-on-demand (DoD) droplet deposition to dispense drug solutions precisely on binder jetting-based 3D printed multi-compartment tablets containing 3 model anti-viral drugs (hydroxychloroquine sulfate - HCS, ritonavir and favipiravir). The printing pressure affected the printing quality whereas the printing speed and infill density significantly impacted the volume dispersed on the tablets. Additionally, the DoD parameters such as nozzle valve open time and cycle time affected both dispersing volume and the uniformity of the tablets. The solid-state characterization, including DSC, XRD, and PLM, revealed that all drugs remained in their crystalline forms. Advanced surface analysis conducted by microCT imaging as well as Artificial Intelligence (AI)/Deep Learning (DL) model validation showed a homogenous drug distribution in the printed tablets even at ultra-low doses. For a four-hour in vitro drug release study, the drug loaded in the outer layer was released over 90%, and the drug incorporated in the middle layer was released over 70%. In contrast, drug encapsulated in the core was only released about 40%, indicating that outer and middle layers were suitable for immediate release while the core could be applied for delayed release. Overall, this study demonstrates a great potential for tailoring drug release rates from a customized modular dosage form and developing personalized drug delivery systems coupling different 3D printing techniques.
Asunto(s)
Antivirales , Tecnología Farmacéutica , Humanos , Tecnología Farmacéutica/métodos , Inteligencia Artificial , Comprimidos/química , Excipientes/química , Liberación de Fármacos , Impresión TridimensionalRESUMEN
INTRODUCTION: Ramulus Mori (RM, Sangzhi) and Cortex Mori (CM, Sangbaipi) both come from the Chinese medicinal plant mulberry tree. CM is usually used to relieve cough, while RM is usually used to treat pain. There are no studies on the quality control of RM and CM based on their analgesic and anti-inflammatory constituents associated with their traditional use. The chemical profiles of CM and RM were confusing. Some CM had similar profiles to RM, but some did not. OBJECTIVE: We aimed to reveal the chemical differences between RM and CM and to evaluate their quality. MATERIALS AND METHODS: Their chemical differences were studied using metabolomic analysis based on UHPLC-ESI-MS data. The contents of five quality marker candidates were determined by UHPLC-PDA. The analgesic activities of morusin and kuwanon C were assessed by an acetic acid-induced writhing test. RESULTS: CM was characterized by chemical diversity, whereas RM had good homogeneity. Four groups of CM were classified based on their chemicals. The chemical profiles of CM group 4 were more similar to that of RM. Eighteen putative features were identified based on an MS-Finder search and fragmentation rules. Content limits for four quality markers with anti-inflammatory or analgesic activities were proposed for RM. Furthermore, a possible biosynthetic relationship between kuwanon C, kuwanon G, and morusin was hypothesized based on the high Pearson coefficient between kuwanon G and morusin. CONCLUSION: The obtained results may be useful in the evaluation of RM and CM and afford insight into the biosynthetic pathway of Diels-Alder adducts in Morus.
Asunto(s)
Medicamentos Herbarios Chinos , Morus , Plantas Medicinales , Antiinflamatorios , Cromatografía Líquida de Alta Presión , Medicamentos Herbarios Chinos/normas , Medicina Tradicional China , Metabolómica , Morus/química , Plantas Medicinales/química , Control de Calidad , ÁrbolesRESUMEN
With the advancements in cutting-edge technologies and rapid development of medical sciences, patient-focused drug development (PFDD) through additive manufacturing (AM) processes is gathering more interest in the pharmaceutical area than ever. Hence, there is an urgent need for researchers to comprehensively understand the influence of three-dimensional design on the development of novel drug delivery systems (DDSs). For this research, fused deposition modeling (FDM) 3D printing was investigated, and phenytoin (PHT) was selected as the model drug. The primary purpose of the current investigation was to understand the influence of AM process on the pharmaceutical products' quality. A series of comparative studies, including morphology, solid-state analysis, and in vitro drug release studies between additive manufactured filaments (printlets) and extruded filaments, were conducted. The FDM-based AM showed adequate reproducibility by manufacturing printlets with consistent qualities; however, the model slicing orientation significantly affected the print qualities. The texture analysis studies showed that the mechanical properties (breaking behavior) of additive manufactured printlets were varied from the extruded filaments. Additionally, the higher printing temperature also influenced the solid state of the drug where the process assisted in PHT's amorphization in the printed products, which further affected their mechanical properties and in vitro drug release performances. The current investigation illustrated that the AM process would change the printed objects' macrostructure over the conventional products, and the printing temperature and slicing will significantly affect the printing process and product qualities.
Asunto(s)
Excipientes , Tecnología Farmacéutica , Liberación de Fármacos , Humanos , Impresión Tridimensional , Reproducibilidad de los Resultados , Comprimidos , TemperaturaRESUMEN
Conventional oral dosage forms may not always be optimal especially for those patients suffering from dysphasia or difficulty swallowing. Development of suitable oral thin films (OTFs), therefore, can be an excellent alternative to conventional dosage forms for these patient groups. Hence, the main objective of the current investigation is to develop oral thin film (OTF) formulations using novel solvent-free approaches, including additive manufacturing (AM), hot-melt extrusion, and melt casting. AM, popularly recognized as 3D printing, has been widely utilized for on-demand and personalized formulation development in the pharmaceutical industry. Additionally, in general active pharmaceutical ingredients (APIs) are dissolved or dispersed in polymeric matrices to form amorphous solid dispersions (ASDs). In this study, acetaminophen (APAP) was selected as the model drug, and Klucel™ hydroxypropyl cellulose (HPC) E5 and Soluplus® were used as carrier matrices to form the OTFs. Amorphous OTFs were successfully manufactured by hot-melt extrusion and 3D printing technologies followed by comprehensive studies on the physico-chemical properties of the drug and developed OTFs. Advanced physico-chemical characterizations revealed the presence of amorphous drug in both HME and 3D printed films whereas some crystalline traces were visible in solvent and melt cast films. Moreover, advanced surface analysis conducted by Raman mapping confirmed a more homogenous distribution of amorphous drugs in 3D printed films compared to those prepared by other methods. A series of mathematical models were also used to describe drug release mechanisms from the developed OTFs. Moreover, the in vitro dissolution studies of the 3D printed films demonstrated an improved drug release performance compared to the melt cast or extruded films. This study suggested that HME combined with 3D printing can potentially improve the physical properties of formulations and produce OTFs with preferred qualities such as faster dissolution rate of drugs.
RESUMEN
BACKGROUND: Anticoagulants are essential in the prevention of venous thromboembolism. However, the effectiveness and safety of different anticoagulants have always been controversial. Therefore, we aimed to expand the sample of anticoagulant results and rank the efficacy and safety of 19 anticoagulants in the prevention of venous thromboembolism when total knee or total hip arthroplasty procedure is performed. METHODS: A systematic review and network meta-analysis of randomized trials of adult patients undergoing total hip or knee arthroplasty were conducted. The trials were identified from PubMed, Web of Science, Cochrane Library, and Embase databases, in which anticoagulants were used as interventions randomized controlled trial. The incidence of venous embolism and bleeding are the key outcomes of assessing the efficacy of intervention drugs. We used the Physical Therapy Evidence Database (PEDro) to assess risk bias and used pairwise comparison and network meta-analysis with random effects to estimate the summary relative risk. The study has been registered with PROSPERO, number CRD42020200747. RESULTS: From the 4083 identified manuscripts, 45,067 participants from 53 randomized trials were included in the analysis and randomly assigned to 19 anticoagulants. With Enoxaparin as a control, Rivaroxaban (risk difference 0.07, 95 % credible interval 0.06 to 0.08), Edoxaban (RD 0.09, 95 % CrI 0.08 to 0.11), and Apixaban (RD 0.05, 95 % CrI 0.04 to 0.06) had the best effect in preventing VTE. However, in terms of comprehensive bleeding rate, Apixaban, Edoxaban, and Darexaban were the most effective and stable. Although effective in preventing VTE, bleeding remains relatively high in Rivaroxaban. Enoxaparin is low-molecular-weight heparin that is widely used in clinics, and although its overall efficacy is not the best, its efficacy and safety are very stable. CONCLUSION: According to the available data, Apixaban, Edoxaban, and Darexaban are better than any anticoagulants in the prevention of VTE and bleeding during total knee or total hip arthroplasty. In our study, Fondaparinux, Eribaxaban, Dalteparin, Betrixaban, Bemiparin, Reviparin, Acenocoumarol, and Tinzaparin were scarce in the included studies, therefore, more evidence is needed to prove their efficacy and safety.
Asunto(s)
Anticoagulantes/uso terapéutico , Artroplastia de Reemplazo de Rodilla , Tromboembolia Venosa/prevención & control , Anticoagulantes/efectos adversos , Artroplastia de Reemplazo de Rodilla/efectos adversos , Enoxaparina/efectos adversos , Enoxaparina/uso terapéutico , Hemorragia/inducido químicamente , Humanos , Pirazoles/efectos adversos , Pirazoles/uso terapéutico , Piridinas/efectos adversos , Piridinas/uso terapéutico , Piridonas/efectos adversos , Piridonas/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Rivaroxabán/efectos adversos , Rivaroxabán/uso terapéutico , Tiazoles/efectos adversos , Tiazoles/uso terapéuticoRESUMEN
Chronic ankle instability predominantly occurs due to multiple exercise-related diseases. Conservative treatment methods regarding this condition have not effectively improved in recent years, which is why more focus has been put on exploring different novel reconstruction procedures of the lateral ankle ligament for the treatment of chronic ankle instability. OBJECTIVES: This study aims to obtain the overall effectiveness of various lateral ankle ligament reconstruction methods for chronic ankle ligament instability. METHODS: We gathered data from PubMed and EMBASE databases using the keywords: ankle, malleolar, and reconstruction. Newcastle - Ottawa quality assessment was carried out for the obtained studies; effect volume combination and image drawing were performed by Stata14, and Excel was used for data statistics. RESULTS: A total of 12 articles were included in the quantitative analysis by performing full-text reading and data inclusion. Among them, 476 patients (485 ankle joints) were treated. The results showed that the overall valid efficiency of "excellent" was 59% and "good" lateral ligament reconstruction was 26%, I2=87.3%, P = 0.000; the subgroup analysis anatomic reconstruction group I2=0.0%, P = 0.993; the autograft group I2=0.0%, P = 1.000; allograft group I2=0.0%, P = 0.993. CONCLUSION: Reconstruction of the lateral ankle ligament is a relatively stable treatment for chronic ankle instability.
Asunto(s)
Traumatismos del Tobillo , Inestabilidad de la Articulación , Ligamentos Laterales del Tobillo , Tobillo , Traumatismos del Tobillo/cirugía , Articulación del Tobillo/cirugía , Humanos , Inestabilidad de la Articulación/cirugía , Ligamentos Laterales del Tobillo/cirugíaRESUMEN
Two rarely phenolic acid-substituted alloses (1, 2) and one new glucoside (3), as well as nine known compounds (4-12) were isolated from rhizomes of Cibotium barometz (L.) J. Sm. Structures of 1-3 were established by extensively spectroscopic analyses (NMR, MS, etc.) and acid hydrolysis. All compounds were evaluated for the hepatoprotective activities against APAP-induced HepG2 cell damage. Compounds 1, 4-7, 10 exhibited significant hepatoprotective activities, even more strongly than positive control, bicycol. In addition, compounds 1 and 9 could reduce PC12 cell death induced by serum deprivation.
Asunto(s)
Helechos/química , Glucosa/análogos & derivados , Glicósidos/química , Hidroxibenzoatos/química , Rizoma/química , Acetaminofén/antagonistas & inhibidores , Acetaminofén/toxicidad , Animales , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Medicamentos Herbarios Chinos/química , Glucosa/química , Glucosa/farmacología , Glicósidos/aislamiento & purificación , Glicósidos/farmacología , Células Hep G2/efectos de los fármacos , Humanos , Hidroxibenzoatos/farmacología , Estructura Molecular , Células PC12 , Sustancias Protectoras/farmacología , RatasRESUMEN
As a recombinant humanized monoclonal antibody that targets the extracellular region of HER2 tyrosine kinase receptor, trastuzumab (TRAZ) has demonstrated comparable clinical efficacy and improved survival in patients with HER2-positive breast cancer. Nevertheless, the therapeutic potential of TRAZ is often limited due to its frequent resistance to anti-HER2 therapy. Therefore, we investigate the reversal effect of STAT3-specific decoy oligonucleotides (STAT3-decoy ODNs) on TRAZ resistance, which contain the consensus sequence within the targeted gene promoter of STAT3. Considering the shortcomings of poor cellular permeability and rapid degradation in vivo limit the further clinical applications of ODNs, we report here an asymmetric hybrid lipid/polymer vesicles with calcium phosphate as the solid kernel (CaP@HA). Through hyaluronan-mediated CD44 targeting, the constructed vesicles can specifically carry STAT3-decoy ODNs into TRAZ-resistant breast cancer cells and then regulate TRAZ-induced apoptosis. In comparison with the native ones, ODNs packaged with CaP@HA showed significantly increased serum stability, cellular transfection, synergistic cytotoxicity and apoptosis in vitro. The improved TRAZ sensitization is attributed to the blockade of STAT3 signaling as well as the expression of downstream target genes associated with TRAZ resistance. With the synergistic action of STAT3-decoy ODNs loaded CaP@HA, TRAZ inhibited the growth of its resistant breast cancer xenograft dramatically and induced significant tumor cell apoptosis in vivo. These results suggested that CaP@HA mediated targeted delivery of STAT3-decoy ODNs might be a promising new strategy to overcome anti-HER2 resistance in breast cancer therapy.