Activation of leukocyte immunoglobulin-like receptor B2 signaling pathway in cortical lesions of pediatric patients with focal cortical dysplasia type IIb and tuberous sclerosis complex

BackgroundsFocal cortical dysplasia type IIb (FCD IIb) and tuberous sclerosis complex (TSC) are very frequently associated with epilepsy in pediatric patients. Human leukocyte immunoglobulin-like receptor B2 (LILRB2) participates in the process of neurite growth, synaptic plasticity, and inflammatory reaction, suggesting a potential role of LILRB2 in epilepsy. However, little is known about the distribution and expression of LILRB2 in cortical lesions of FCD IIb and cortical tubers of TSC.MethodsIn this study, we have described the distribution and expression of LILRB2 signaling pathway in cortical lesions of pediatric patients with FCD IIb (n = 15) and TSC (n = 12) relative to age-matched autopsy control samples (CTX, n = 10), respectively. The protein levels of LILRB2 pathway molecules were assessed by western blotting and immunohistochemistry. The expression pattern was investigated by immunohistochemistry and double labeling experiment. Spearman correlation analysis to explore the correlation between LILRB2 protein level and seizure frequency.ResultsThe protein levels of LILRB2 and its downstream molecules POSH, SHROOM3, ROCK1, ROCK2 were increased in cortices of patients compared to CTX. Protein levels of LILRB2 negatively correlated with the frequency of seizures in FCD IIb and TSC patients, respectively. Moreover, all LILRB2 pathway molecules were strongly expressed in dysmorphic neurons, balloon cells, and giant cells, LILRB2 co-localized with neuron marker and astrocyte marker.ConclusionTaken together, the special expression patterns of LILRB2 signaling pathway in cortical lesions of FCD IIb and TSC implies that it may be involved in the process of epilepsy.     

Effect of carbon-rich biochar on mechanical properties of PLA-biochar composites

Agricultural biomass residues are emerged from harvesting and processing of agricultural crops. When the crop production increases, a large amount of biomass residues is produced and remained after cutting of peel, bunch, straw and stalk of crops. In this work, agricultural biomass residues (cassava rhizome, durian peel, pineapple peel and corncob) were selected as feedstock for carbon-rich biochar (CRB) production using a facile pyrolysis method. Proximate analysis and thermogravimetric analysis (TGA) were used to characterize biomass feedstock. The results showed that the percentage of fixed carbon in biomass feedstock ranged between 11.91% and 17.51%. Characteristic differences of the CRB were investigated using scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDS), Fourier transform infrared spectroscopy (FTIR) and Raman spectroscopy. The carbon content in the CRB was found to significantly depend on biomass origin. Interestingly, cassava rhizome, which has a higher percentage of fixed carbon, is a superior precursor for CRB production. The study of different pyrolysis temperature indicated that the carbon content of cassava rhizome derived CRB is increased with pyrolysis temperature. The tensile properties of composite between poly(lactic acid) PLA and different types of biomass-derived CRB were investigated. PLA composite incorporated with a higher carbon content-CRB tended to exhibit improved mechanical properties. Specifically, the elastic modulus and impact energy of PLA/CRB composite specimens increased remarkably with the incorporation of CRB powder. The current research indicates that CRB prepared from agricultural biomass residues could be a sustainable material for utilization in PLA biocomposites.     

The clinicopathologic spectrum of segmental membranous glomerulopathy

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Sustained Release of Minocycline From Minocycline-Calcium-Dextran Sulfate Complex Microparticles for Periodontitis Treatment

It is important to address the periodontitis-associated bacteria in the residual subgingival plaque after scaling and root planing to successfully treat periodontitis. In this study, we explored the possibility of exploiting the ion pairing/complexation of minocycline, Ca²⁺, and sulfate/sulfonate-bearing biopolymers to develop an intrapocket delivery system of minocycline as an adjunct to scaling and root planing. Minocycline-calcium-dextran sulfate complex microparticles were synthesized from minocycline, CaCl₂, and dextran sulfate. They were characterized using Fourier-transform infrared spectroscopy, scanning electron microscopy, and energy-dispersive X-ray spectroscopy. An in vitro release study was conducted to evaluate the release kinetics of minocycline from these microparticles. Agar disk diffusion assays and biofilm-grown bacteria assays were used to assess antibacterial capability. High loading efficiency (96.98% ± 0.12%) and high loading content (44.69% ± 0.03%) for minocycline were observed for these complex microparticles. Mino-Ca-DS microparticles achieved sustained release of minocycline for at least 9 days at pH 7.4 and 18 days at pH 6.4 in phosphate-buffered saline, respectively. They also demonstrated potent antimicrobial effects against Streptococcus mutans and Aggregatibacter actinomycetemcomitans in agar disk diffusion and biofilm assays. These results suggested that the ion pairing/complexation of minocycline, Ca²⁺, and sulfonate/sulfate-bearing biopolymers can be exploited to develop complex microparticles as local delivery systems for periodontitis treatment.     

Nanofiber technology in the ex vivo expansion of cord blood-derived hematopoietic stem cells

Umbilical cord blood (CB) can be used as an alternative source of hematopoietic stem cells (HSCs) for transplantation in hematological and non-hematological disorders. Despite several recognized advantages the limited cell number in CB one unit still restricts its clinical use. The success of transplantation greatly depends on the levels of total nucleated cell and CD34+ cell counts. Thus, many ex vivo strategies have been developed within the last decade in order to solve this obstacle, with more or less success, mainly determined by the degree of difficulty related with maintaining HSCs self-renewal and stemness properties after long-term expansion. Different research groups have developed very promising and diverse CB-derived HSC expansion strategies using nanofiber scaffolds. Here we review the state-of-the-art of nanofiber technology-based CB-derived HSC expansion.     

Lipid based nanocarriers: a translational perspective

Over the recent couple of decades, pharmaceutical field has embarked most phenomenal noteworthy achievements in the field of medications as well as drug delivery. The rise of Nanotechnology in this field has reformed the existing drug delivery for targeting, diagnostic, remedial applications and patient monitoring. The convincing usage of nanotechnology in the conveyance of medications that prompts an extension of novel lipid-based nanocarriers and non-liposomal systems has been discussed. Present review deals with the late advances and updates in lipidic nanocarriers, their formulation strategies, challenging aspects, stability profile, clinical applications alongside commercially available products and products under clinical trials. This exploration may give a complete idea viewing the lipid based nanocarriers as a promising choice for the formulation of pharmaceutical products, the challenges looked by the translational process of lipid-based nanocarriers and the combating methodologies to guarantee the headway of these nanocarriers from bench to bedside.     

Nanoformulations of anticancer FGFR inhibitors with improved therapeutic index

Fibroblast growth factor receptor (FGFR) inhibitors like ponatinib and nintedanib are clinically approved for defined cancer patient cohorts but often exert dose-limiting adverse effects. Hence, we encapsulated the FGFR inhibitors ponatinib, PD173074, and nintedanib into polylactic acid nanoparticles and liposomes to enable increased tumor accumulation/specificity and reduce side effects. Different methods of drug loading were tested and the resulting formulations compared regarding average size distribution as well as encapsulation efficiency. Appropriate encapsulation levels were achieved for liposomal preparations only. Nanoencapsulation resulted in significantly decelerated uptake kinetics in vitro with clearly decreased short-term (up to 72?h) cytotoxicity at higher concentrations. However, in long-term clonogenic assays liposomal formations were equally or even more active as compared to the free drugs. Accordingly, in an FGFR inhibitor-sensitive murine osteosarcoma transplantation model (K7M2), only liposomal but not free ponatinib resulted in significant tumor growth inhibition (by 60.4%) at markedly reduced side effects.     

基因重组人骨形成蛋白-2和牛骨形成蛋白异位诱导成骨的比较

目的：观察基因重组人骨形成蛋白-2（rhBMP-2)和牛骨形成蛋白（bBMP)分别与珊瑚/聚乳酸形成复合人工骨的异位诱导成骨活性，同时比较两种骨形成蛋白的成骨效率，方法：把rhBMP-2和bBMP分别与珊瑚/聚乳酸形成复合人工骨，进行小鼠肌内种植1、3、6周后，组织学观察和组织形态测量，比较其异位诱导成骨活性。结果：rhBMP-2和bBMP存在骨诱导差异，rhBMP-2诱导成骨量相对较少但血管，骨髓含量丰富，bBMP则相反，结论：两种BMP都具有良好的诱骨活性，但在居骨量和血管，骨髓样组织的形成量上有明显不同。     

复合人工骨双重机制修复骨质缺损的实验研究

目的　研究生物珊瑚 /聚乳酸和rhBMP 2合成人工骨 (复合骨 )修复兔颅骨缺损的骨修复能力。方法　选择 2 4只新西兰兔 ,随机分成 2组 ,每组 1 2只 ,建立兔颅骨缺损标准模型。植入复合骨 ,用珊瑚 /聚乳酸作为对照。术后 4、8、1 2周每组各处死 4只动物。进行X线片、组织学观察。结果　复合骨在植入缺损后 ,不仅在其周边部有骨组织长入 ,而且在整个植入物内均有新骨形成 ,即出现多中心成骨。复合骨在同一时间点的成骨量明显多于对照组 ,随时间推移 ,成骨量递增。结论　生物珊瑚 /聚乳酸和rhBMP 2合成人工骨在体内以传导成骨和诱导成骨双重机制完成骨修复 ,作为植骨材料具有良好的应用前景