MatrisomeDB 2.0: 2023 updates to the ECM-protein knowledge database.

The extracellular matrix (ECM) is a complex assembly of proteins that constitutes the scaffold organizing cells, tissues, and organs. Over the past decade, mass-spectrometry-based proteomics has become the method of choice to profile the composition of the ECM, or the matrisome, of tissues. To assist non-specialists with the reuse of ECM proteomic datasets, we released MatrisomeDB (https://matrisomedb.org) in 2020. Here, we report the expansion of the database to include 25 new curated studies on the ECM of 24 new tissues in addition to datasets on tissues previously included, more than doubling the size of the original database and achieving near-complete coverage of the in-silico predicted matrisome. We further enhanced data visualization by maps of peptides and post-translational-modifications detected onto domain-based representations and 3D structures of ECM proteins. We also referenced external resources to facilitate the design of targeted mass spectrometry assays. Last, we implemented an abstract-mining tool that generates an enrichment word cloud from abstracts of studies in which a queried protein is found with higher confidence and higher abundance relative to other studies in MatrisomeDB.

Multi-modal Profiling of the Extracellular Matrix of Human Fallopian Tubes and Serous Tubal Intraepithelial Carcinomas.

Recent evidence supports the fimbriae of the fallopian tube as one origin site for high-grade serous ovarian cancer (HGSOC). The progression of many solid tumors is accompanied by changes in the microenvironment, including alterations of the extracellular matrix (ECM). Therefore, we sought to determine the ECM composition of the benign fallopian tube and changes associated with serous tubal intraepithelial carcinomas (STICs), precursors of HGSOC. The ECM composition of benign human fallopian tube was first defined from a meta-analysis of published proteomic datasets that identified 190 ECM proteins. We then conducted de novo proteomics using ECM enrichment and identified 88 proteins, 7 of which were not identified in prior studies (COL2A1, COL4A5, COL16A1, elastin, LAMA5, annexin A2, and PAI1). To enable future in vitro studies, we investigated the levels and localization of ECM components included in tissue-engineered models (type I, III, and IV collagens, fibronectin, laminin, versican, perlecan, and hyaluronic acid) using multispectral immunohistochemical staining of fimbriae from patients with benign conditions or STICs. Quantification revealed an increase in stromal fibronectin and a decrease in epithelial versican in STICs. Our results provide an in-depth picture of the ECM in the benign fallopian tube and identified ECM changes that accompany STIC formation. (J Histochem Cytochem XX: XXX-XXX, XXXX).

Corrigendum to "Alkyl Length Effects on the DNA Transport Properties of Cu (II) and Zn(II) Metallovesicles: An In Vitro and In Vivo Study".

[This corrects the article DOI: 10.1155/2018/2851579.].

Alkyl Length Effects on the DNA Transport Properties of Cu (II) and Zn(II) Metallovesicles: An In Vitro and In Vivo Study.

Cationic liposomes with DNA-transportation properties have attracted considerable attention for their ability to deliver medicinal oligonucleotides to mammalian cells. Amongst these are metalloliposomes that use transition metal ions to confer the lipid molecules cationic charge and unique advantages such as redox- and ligand-exchange triggered DNA-release properties. In this study, lipophilic copper (II) and zinc (II) complexes of 1-alkyl-1,4,7-triazacyclononane were prepared to investigate their ability to bind and transfect double stranded DNA with mammalian cells in vitro and in vivo. The copper(II)-surfactant complexes Cu(TACN-C8)2 (1), Cu(TACN-C10)2 (2), Cu(TACN-C12)2 (3), Cu(TACN-C14)2 (4), Cu(TACN-C16)2 (5), and Cu(TACN-C18)2 (6) that comprise ligands that vary in the length of the alkyl group and the zinc (II)-surfactant complex of Zn(TACN-C12)2 (7) were synthesized. The critical micelle concentration (CMC) for 1-7 was measured using fluorescence spectroscopy and an evaluation of the transfection efficiency of the complexes was assessed using the pEGFP-N1 plasmid and HEK 293-T cells. An inverse relationship between DNA transfection efficiency and CMC of the Cu(II) metallosurfactants was observed. The highest transfection efficiency of 38% was observed for Cu(TACN-C12)2 corresponding to the surfactant with dodecyl alkyl chain having a CMC of 50 µM. Further, an in vivo experiment using mice models was conducted to test the Cu(TACN-C12)2 (3) and Zn(TACN-C12)2 (7) metallosurfactants delivering a DNA vaccine designed for protection against leishmaniasis disease and the study revealed that the Cu-lipoplex elicited the production of significantly more T cells than the Zn-lipoplex and the control group in vivo.

A Novel Stool PCR Test for Helicobacter pylori May Predict Clarithromycin Resistance and Eradication of Infection at a High Rate.

Clarithromycin-based regimens are commonly used as a first-line therapy for Helicobacter pylori-positive patients; however, resistance to clarithromycin has led to treatment failures. The aim of this study was to evaluate the feasibility of using stool samples to detect the presence of H. pylori DNA while concurrently detecting mutations associated with resistance to clarithromycin. For this purpose, total DNA was extracted from 294 raw stool specimens from H. pylori-positive and -negative patients. TaqMan real-time PCR amplification was used to detect the presence of H. pylori as well as to predict the phenotype of the organism and the related outcome for patients treated with clarithromycin. Clarithromycin resistance was determined upon analysis of the PCR result. Patients were also tested by a urea breath test and were subjected to esophagogastroduodenoscopy, followed by histology, culture, and a rapid urease test, in order to obtain a consensus patient infection status. Of 294 total stool samples, 227 were deemed true positive. The sensitivity of H. pylori detection by PCR was 93.8%. Of 213 true-positive samples that were sequenced, 36.2% showed point mutations associated with clarithromycin resistance (A2142C, A2142G, A2143G). The final correlation of the mutant genotypes as determined by sequencing with the eradication of infection was 86%. We found that Helicobacter pylori DNA can be detected in human stool specimens with high sensitivity and can therefore be used to determine the presence of the bacterium without obtaining a biopsy sample. Moreover, genotypic resistance to clarithromycin can be predicted without obtaining a biopsy sample, facilitating the choice of the right therapeutic approach.

Particle-particle interactions between layered double hydroxide nanoparticles.

Changes in chemical properties of nanoscale particles include quantum size effect, changes in the cell parameters and lattice symmetry, and surface and interface effects. In the case of layered double hydroxides (LDHs), surface and interface effects dominate for nanoparticles of MgAl LDHs. Using TEM micrographs of nanoparticle-sized LDHs, we have found that the increased number of surface atoms relative to the internal atoms increases the surface-to-surface interparticle attractions. As a result, nanosize LDH particles are able to form continuous oriented films that adhere well to a polar substrate.