MOF materials, the new family of the molecular sieves with exceptional properties and possible applications

The metal organic frameworks (MOFs) are a novel group of molecular sieves discovered in the last decade of the twentieth century. Most of conventional molecular sieves such as microporous zeolites and zeolite-like materials, ordered mesoporous materials (M41S) are typical inorganic compounds. Although their synthesis often involves an assistance of organic compounds acting as structure directing agents and organic solvents are sometimes applied during their crystallization, the organics are always removed from resulted products (mainly by calcinations). The MOFs are crystalline materials build of metal ions or ion clusters coordinatively bonded with organic segments (linkers) that form porous (one-, two-, or threedimensional) structures. The various coordination number of selected metal and the nature of organic linkers allow to prepare a great variety of structures with different properties. The inorganic components comprise a great variety of transition (e.g. Zn Cu, Fe, rare earths) and base metal (e.g. Al) cations of different valence. The organic linkers are functionalized compounds containing O, N, P, S atoms (i.e. carboxylates, phosphonates, sulfonates, cyanides, amines, imidazoles) enable to chelate the inorganic cations. The organic subunits can be additionally modified by substitution of other functional groups (halogens, hydroxyls, aminogroups). The MOF materials are mostly prepared similarly as zeolitic materials by crystallization in solvothermal conditions. The solvents (water or organic compounds) can play a role of templates, although sometimes additional structure directing agents are admitted into the initial mixtures. The crystallization is always conducted in moderate temperatures (20–200°C). After removal of solvents well ordered pore systems are available for selective adsorption and for other applications. The thermal stability of this family of molecular sieves is obviously lower than that of inorganic materials, but most of them can withstand heating at 350–400°C, which still makes them suitable for variety of potential applications. The adsorption properties of MOFs makes them very appealing for practical application. The recorded surface areas of some types are overwhelming and they surpass 5000 m2/g. The high adsorption capacity is very promising for storage of fuels (natural gas, hydrogen) or waste gases (CO2, SO2) as well as for their separation. The great and very fast growing variety of structures and chemical compositions brings also a hope to use them as efficient catalysts. The metal segments, functional groups in organic blocks as well as occluded or encapsulated species can play a role of catalytically active sites. The MOF materials can be also applied as matrices for sensors, pigments, and microelectronic or optical devices

The role of DnaK/DnaJ and GroEL/GroES systems in the removal of endogenous proteins aggregated by heat-shock from Escherichia coli cells

AbstractThe submission of Escherichia coli cells to heat-shock (45°C, 15 min) caused the intracellular aggregation of endogenous proteins. In the wt cells the aggregates (the S fraction) disappeared 10 min after transfer to 37°C. In contrast, the S fraction in the dnaK and dnaJ mutant strains was stable during approximately one generation time (45 min). This demonstrated that neither the renaturation nor the degradation of the denatured proteins was possible in the absence of DnaK and DnaJ. The groEL44 and groES619 mutations stabilised the aggregates to a lesser extent. It was shown by the use of cloned genes, dnaK/dnaJ or groEL/groES, producing the corresponding proteins in about 4-fold excess, that the appearance of the S fraction in the wt strain resulted from a transiently insufficient supply of the heat-shock proteins. Overproduction of the GroEL/GroES proteins in dnaK756 or dnaJ259 background prevented the aggregation, however, overproduction of the DnaK/DnaJ proteins did not prevent the aggregation in the groEL44 or groES619 mutant cells although it accelerated the disappearance of the aggregates. The properties of the aggregated proteins are discussed from the point of view of their competence to renaturation/degradation by the heat-shock system

Effects of an immunosuppressive treatment on the rat prostate

Marta Grabowska,1 Karolina Kędzierska,2 Katarzyna Michałek,3 Sylwia Słuczanowska-Głąbowska,4 Maciej Grabowski,5 Małgorzata Piasecka,1 Andrzej Kram,6 Iwona Rotter,7 Aleksandra Rył,1 Maria Laszczyńska1 1Department of Histology and Developmental Biology, Pomeranian Medical University, 2Department of Nephrology, Transplantology and Internal Medicine, Pomeranian Medical University, 3Department of Physiology, Cytobiology and Proteomics, West Pomeranian University of Technology, 4Department of Physiology, Pomeranian Medical University, 5Department of Microbiology and Applied Biotechnology, West Pomeranian University of Technology, 6Department of Pathology, West Pomeranian Oncology Center, 7Department of Medical Rehabilitation, Pomeranian Medical University, Szczecin, Poland Abstract: The aim of this study was to determine the influence of different combinations of immunosuppressive drugs on the morphology, ultrastructure, and expression of proliferating cell nuclear antigen and cytoskeleton proteins in the rat dorsolateral prostate. The studies were conducted on 48 male Wistar rats. The animals were divided into eight groups: a control group and seven experimental groups. For 6 months, the animals in the experimental groups were administered a combination of drugs including rapamycin (Rapa), cyclosporin A, tacrolimus (Tac), mycophenolate mofetil, and prednisone (Pred), according to the standard three-drug regimens for immunosuppressive therapy used in clinical practice. An evaluation of the morphology and ultrastructure was conducted, and a quantitative evaluation of the expression of proliferating cell nuclear antigen and desmin- and cytokeratin-positive cells with weak, moderate, and strong expression was performed. The combination of Rapa, Tac, and Pred caused the smallest morphological and ultrastructural changes in the rat prostate cells. In the case of rats whose treatment was switched to Rapa monotherapy, a decreased percentage of proliferating cells of both the glandular epithelium and the stroma was found. Decreases in body weight and changes in the expression of cytokeratin and desmin were observed in all the experimental rats. The combination of Rapa, Tac, and Pred would seem to be the most beneficial for patients who do not suffer from prostate diseases. Our results justify the use of inhibitors of the mammalian target of Rapa in the treatment of patients with prostate cancer. The changes in the expression of cytoskeleton proteins may be the result of direct adverse effects of the immunosuppressive drugs, which are studied in this article, on the structure and organization of intermediate filament proteins. Keywords: rat prostate, ultrastructure, cytokeratin, desmin, PCNA, immunosuppressant

Chimeric stimuli-responsive liposomes as nanocarriers for the delivery of the anti-glioma agent TRAM-34

Nanocarriers are delivery platforms of drugs, peptides, nucleic acids and other therapeutic molecules that are indicated for severe human diseases. Gliomas are the most frequent type of brain tumor, with glioblastoma being the most common and malignant type. The current state of glioma treatment requires innovative approaches that will lead to efficient and safe therapies. Advanced nanosystems and stimuli-responsive materials are available and well-studied technologies that may contribute to this effort. The present study deals with the development of functional chimeric nanocarriers composed of a phospholipid and a diblock copolymer, for the incorporation, delivery and pH-responsive release of the antiglioma agent TRAM-34 inside glioblastoma cells. Nanocarrier analysis included light scattering, protein incubation and electron microscopy, and flu-orescence anisotropy and thermal analysis techniques were also applied. Biological assays were carried out in order to evaluate the nanocarrier nanotoxicity in vitro and in vivo, as well as to evaluate antiglioma activity. The nanosystems were able to successfully manifest functional properties under pH conditions, and their biocompatibility and cellular internalization were also evident. The chimeric nanoplatforms presented herein have shown promise for biomedical applications so far and should be further studied in terms of their ability to deliver TRAM-34 and other therapeutic molecules to glioblastoma cells. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

Chimeric stimuli-responsive liposomes as nanocarriers for the delivery of the anti-glioma agent TRAM-34

Nanocarriers are delivery platforms of drugs, peptides, nucleic acids and other therapeutic molecules that are indicated for severe human diseases. Gliomas are the most frequent type of brain tumor, with glioblastoma being the most common and malignant type. The current state of glioma treatment requires innovative approaches that will lead to efficient and safe therapies. Advanced nanosystems and stimuli-responsive materials are available and well-studied technologies that may contribute to this effort. The present study deals with the development of functional chimeric nanocarriers composed of a phospholipid and a diblock copolymer, for the incorporation, delivery and pH-responsive release of the antiglioma agent TRAM-34 inside glioblastoma cells. Nanocarrier analysis included light scattering, protein incubation and electron microscopy, and flu-orescence anisotropy and thermal analysis techniques were also applied. Biological assays were carried out in order to evaluate the nanocarrier nanotoxicity in vitro and in vivo, as well as to evaluate antiglioma activity. The nanosystems were able to successfully manifest functional properties under pH conditions, and their biocompatibility and cellular internalization were also evident. The chimeric nanoplatforms presented herein have shown promise for biomedical applications so far and should be further studied in terms of their ability to deliver TRAM-34 and other therapeutic molecules to glioblastoma cells. © 2021 by the authors. Licensee MDPI, Basel, Switzerland