No abstract

Cathepsin B is a papain-family cysteine protease that is normally located in lysosomes, where it is involved in the turnover of proteins and plays various roles in maintaining the normal metabolism of cells. This protease has been implicated in pathological conditions, e.g., tumor progression and arthritis. In disease conditions, increases in the expression of cathepsin B occur at both the gene and protein levels. At the gene level, the altered expression results from gene amplification, elevated transcription, use of alternative promoters and alternative splicing. These molecular changes lead to increased cathepsin B protein levels and in turn redistribution, secretion and increased activity. Here we focus on the molecular regulation of cathepsin B and attendant implications for tumor progression and arthritis. The potential of cathepsin B as a therapeutic target is also discussed.

Nearly monodispersed FeNi3 submicrometre spheres with an average diameter of 220 nm were synthesized by a simple low temperature reduction method. SiO2@FeNi3 core–shell structured submicrometre spheres with 25 nm thick SiO2 shell were then fabricated by a sol–gel process. A significant enhancement of electromagnetic absorption (EMA) performance was achieved by the silica coating over the 2–18 GHz. The reflection loss (RL) exceeding −20 dB of the composite was obtained over 6.7–15.1 GHz by choosing an appropriate sample thickness between 2.1 and 3.3 mm, and an optimal RL of −61.3 dB was obtained at 8.7 GHz with a thin absorber thickness of 2.9 mm. The coating of the dielectric silica shell significantly enhanced the EMA performance due to the enhancement of interface polarization at the alloys and dielectric interfaces.

Biomimetic cell membrane coated nanoparticles (NPs) with desirable features have been extensively applied for various personalized biomedicine. However, there have not been relative explorations by employing the membrane nanocomplexes for small interfering RNA (siRNA) delivery. Herein, Fe 3 O 4 @PDA NPs with good photothermal capability were applied for efficient siRNA loading and delivery, which were then coated by mesenchymal stem cells (MSCs) to form a membrane. The data showed that MSCs membrane coated Fe 3 O 4 @PDA−siRNA NPs (Fe 3 O 4 @PDA−siRNA@MSCs) maintained the photothermal functionality and the capability of magnetic resonance imaging inherited from Fe 3 O 4 @PDA. The synthesized nanocomplexes exhibited excellent abilities in the delivery of siRNA into DU145 cells. Furthermore, Fe 3 O 4 @PDA−siRNA@MSCs NPs delivering siRNA against Plk1 gene could inhibit the expression of endogenous Plk1 gene and cause obvious apoptosis in DU145 cells. The synergistic combination of photothermal treatment and gene silencing showed obvious antitumor efficacy in a DU145 xenograft mice model. On the basis of preliminary in vitro and in vivo studies, Fe 3 O 4 @PDA−siRNA@MSCs NPs hold considerable promise as a carrier for gene and photothermal therapy.

Cathepsin B expression is increased at both the mRNA and protein levels in a wide variety of tumors. The mechanisms responsible for this regulation are not well elucidated. We have isolated a 2.2-kb cathepsin B genomic fragment that contains the 5'-flanking region of the cathepsin B gene. Using reporter gene analysis in human glioblastoma U87MG cells, we have mapped a 228-bp fragment (-172 to +56) having high promoter activity. This promoter region has a high G+C content; contains potential Spl, Ets, and USF binding motifs; and lacks canonical TATA and CAAT boxes immediately upstream of the major transcriptional initiation site. Cotransfection experiments demonstrated that Spl and Ets1 could trans-activate cathepsin B transcription, whereas Ets2 could not. Electrophoretic mobility shift assays and supershift assays revealed that three of the four putative Sp1 sites in this promoter region form a specific complex containing the Sp1 transcription factor. Mutating all four of the Spl binding sites individually markedly reduced the promoter activity of transfected reporter genes in U87 cells. Cotransfection of this cathepsin B promoter construct with Spl family expression vectors in Schneider's Drosophila line 2 (SL2) cells demonstrated that Spl and Sp3, but not Sp4, activated cathepsin B transcription. Taken together, these results suggest that Sp1, Sp3, and Ets1 are important factors in cathepsin B transcription. The regulation of cathepsin B transcription by Sp1- and Sp1-related factors is mediated through multiple GC boxes.

The interfacial Dzyaloshinskii-Moriya interaction (DMI) in ferromagnetic/heavy metal ultra-thin film structures has attracted a lot of attention thanks to its capability to stabilize Néel-type domain walls (DWs) and magnetic skyrmions for the realization of non-volatile memory and logic devices. In this study, we demonstrate that magnetic properties in perpendicularly magnetized Ta/Pt/Co/MgO/Pt heterostructures, such as magnetization and DMI, can be significantly influenced by the MgO thickness. To avoid the excessive oxidation of Co, an ultrathin Mg layer is inserted to improve the quality of the Co-MgO interface. By using field-driven domain wall expansion in the creep regime, we find that non-monotonic tendencies of the DMI field appear when changing the thickness of MgO. With the insertion of a monatomic Mg layer, the strength of the DMI could reach a high level and saturate. We conjecture that the efficient control of the DMI is a result of subtle changes of both Pt/Co and Co/MgO interfaces, which provides a method to optimize the design of ultra-thin structures achieving skyrmion electronics.

Proteases play important roles in modulating a wide range of cellular functions, in the regulation of biologic processes, and in the pathogenesis of various diseases. Several molecular techniques are available to identify and characterize proteases in cells and tissues. Most of these techniques do not provide information on the activity of proteases in tissues. In situ zymography (ISZ) is a relatively low-cost technique that uses specific protease substrates to detect and localize specific protease activities in tissue sections. Used in combination with other techniques, ISZ provides data that further our understanding of the role of specific proteases in various pathologic and physiologic conditions. This review describes the general principle of ISZ and highlights the past and future applications of this technique in molecular pathology.

Background-African American patients suffer disproportionately from uncontrolled asthma. Treatment with an inhaled corticosteroid (ICS) is considered first-line therapy for persistent asthma.