The complete chloroplast genome of Morus alba (Moraceae: Morus), the herbal medicine species in China

Morus alba is commonly called white mulberry, which is native to China and is the tender branch of mulberry as a herbal medicine in China. In this study, we presented and annotated the complete chloroplast genome of M. alba. The whole chloroplast genome is 159,050 bp in size, exhibiting a large single copy region (87,762 bp), a small single-copy region (19,876 bp) and a pair of inverted-repeat regions (25,706 bp). The overall nucleotide composition is: 31.4% of A, 32.4% of T, 18.4% C, and 17.8% G, with a total A + T content of the chloroplast genome 63.8% and G + C content of 36.2%. The whole chloroplast genome of M. alba contains 126 genes, including 82 protein-coding genes (PCG), 36 transfer RNA (tRNAs), and 8 ribosome RNA (rRNAs). Phylogenetic Maximum-Likelihood (ML) tree based on 15 species chloroplast genomes that Morus alba is closely related to Morus cathayana. This complete chloroplast genomes can be used for medicinal value and clinical drug development that also can have a great significance for future to continue research

Systematic gene therapy derived from an investigative study of AAV2/8 vector gene therapy for Fabry disease

Abstract Background Fabry disease (FD) is a progressive multisystemic disease characterized by a lysosomal enzyme deficiency. A lack of α-galactosidase A (α-Gal A) activity results in the progressive systemic accumulation of its substrates, including globotriaosylceramide (Gb3) and globotriaosylsphingosine (Lyso-Gb3), which results in renal, cardiac, and/or cerebrovascular disease and early death. Enzyme replacement therapy (ERT) is the current standard of care for FD; however, it has important limitations, including a low half-life, limited distribution, and requirement of lifelong biweekly infusions of recombinant enzymes. Methods Herein, we evaluated a gene therapy approach using an episomal adeno-associated viral 2/8 (AAV2/8) vector that encodes the human GLA cDNA driven by a liver-specific expression cassette in a mouse model of FD that lacks α-Gal A activity and progressively accumulates Gb3 and Lyso-Gb3 in plasma and tissues. Results A pharmacology and toxicology study showed that administration of AAV2/8-hGLA vectors (AAV2/8-hGLA) in FD mice without immunosuppression resulted in significantly increased plasma and tissue α-Gal A activity and substantially normalized Gb3 and Lyso-Gb3 content. Conclusions Moreover, the plasma enzymatic activity of α-Gal A continued to be stably expressed for up to 38 weeks and sometimes even longer, indicating that AAV2/8-hGLA is effective in treating FD mice, and that α-Gal A is continuously and highly expressed in the liver, secreted into plasma, and absorbed by various tissues. These findings provide a basis for the clinical development of AAV2/8-hGLA

Development of Lanzyme as the Potential Enzyme Replacement Therapy Drug for Fabry Disease

Fabry disease (FD) is a progressive multisystemic disease characterized by lysosomal enzyme deficiency. Enzyme replacement therapy (ERT) is one of the most significant advancements and breakthroughs in treating FD. However, limited resources and the high cost of ERT might prevent patients from receiving prompt and effective therapy, thereby resulting in severe complications. Future progress in ERT can uncover promising treatment options. In this study, we developed and validated a recombinant enzyme (Lanzyme) based on a CHO-S cell system to provide a new potential option for FD therapy. Our results indicated that Lanzyme was heavily glycosylated, and its highest activity was similar to a commercial enzyme (Fabrazyme®). Our pharmacokinetic assessment revealed that the half-life of Lanzyme was up to 11 min, which is nearly twice that of the commercial enzyme. In vivo experiments revealed that Lanzyme treatment sharply decreased the accumulation levels of Gb3 and lyso-Gb3 in various tissues of FD model mice, with superior or comparable therapeutic effects to Fabrazyme®. Based on these data, Lanzyme may represent a new and promising treatment approach for FD. Building this enzyme production system for ERT can offer additional choice, potentially with enhanced efficacy, for the benefit of patients with FD

Calmodulin-dependent Protein Kinase II/cAMP Response Element-binding Protein/Wnt/β-Catenin Signaling Cascade Regulates Angiotensin II-induced Podocyte Injury and Albuminuria

Close view of the attic story; A commission that involved Borromini as an architect of both churches and palazzi was the Collegio di Propaganda Fide, the headquarters of the Catholic missionary congregation. Although he took charge of building work in 1646, his greatest contributions to shaping the palazzo belong to his last creative years. The complex includes a dormitory and chapel as well. The College was founded by Urbanus VIII for the training of missionaries. The palace is still devoted to its original purpose, but the ground floor has been converted to shopping. The facade over the Piazza di Spagna is by Bernini, whereas Borromini designed the convex and concave entrance facade facing Via Propaganda. Source: Grove Art Online; http://www.groveart.com/ (accessed 12/2/2007

Adiponectin Suppresses Metastasis of Nasopharyngeal Carcinoma through Blocking the Activation of NF-κB and STAT3 Signaling

Adiponectin is an adipocytokine with anti-inflammatory and anticancer properties. Our previous study has shown that blood adiponectin levels were inversely correlated to the risk of nasopharyngeal carcinoma (NPC), and that adiponectin could directly suppress the proliferation of NPC cells. However, the effect of adiponectin on NPC metastasis remains unknown. Here, we revealed in clinical studies that serum adiponectin level was inversely correlated with tumor stage, recurrence, and metastasis in NPC patients, and that low serum adiponectin level also correlates with poor metastasis-free survival. Coculture with recombinant adiponectin suppressed the migration and invasion of NPC cells as well as epithelial–mesenchymal transition (EMT). In addition, recombinant adiponectin dampened the activation of NF-κB and STAT3 signaling pathways induced by adipocyte-derived proinflammatory factors such as leptin, IL-6, and TNF-α. Pharmacological activation of adiponectin receptor through its specific agonist, AdipoRon, largely stalled the metastasis of NPC cells. Taken together, these findings demonstrated that adiponectin could not only regulate metabolism and inhibit cancer growth, but also suppress the metastasis of NPC. Pharmacological activation of adiponectin receptor may be a promising therapeutic strategy to stall NPC metastasis and extend patients’ survival

Micropatterning Extracellular Matrix Proteins on Electrospun Fibrous Substrate Promote Human Mesenchymal Stem Cell Differentiation Toward Neurogenic Lineage

In this study, hybrid micropatterned grafts constructed via a combination of microcontact printing and electrospinning techniques process were utilized to investigate the influencing of patterning directions on human mesenchymal stem cells (hMSCs) differentiation to desired phenotypes. We found that the stem cells could align and elongate along the direction of the micropattern, where they randomly distributed on nonmicropatterned surfaces. Concomitant with patterning effect of component on stem cell alignment, a commensurate increase on the expression of neural lineage commitment markers, such as microtubule associated protein 2 (MAP2), Nestin, NeuroD1, and Class III β-Tubulin, were revealed from mRNA expression by quantitative Real Time PCR (qRT-PCR) and MAP2 expression by immunostaining. In addition, the effect of electrospun fiber orientation on cell behaviors was further examined. An angle of 45° between the direction of micropatterning and orientation of aligned fibers was verified to greatly prompt the outgrowth of filopodia and neurogenesis of hMSCs. This study demonstrates that the significance of hybrid components and electrospun fiber alignment in modulating cellular behavior and neurogenic lineage commitment of hMSCs, suggesting promising application of porous scaffolds with smart component and topography engineering in clinical regenerative medicine