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Sarka Salajkova,1,2 Filip Havel,1,3 Michal Sramek,1 Filip Novotny,1,4 David Malinak,2,5 Rafael Dolezal,2,5 Lukas Prchal,2 Marketa Benkova,2 Ondrej Soukup,2 Kamil Musilek,2,5 Kamil Kuca,2,5 Jiri Bartek,1,6,7 Jan Proska,3 Monika Zarska,1 Zdenek Hodny1 1Department of Genome Integrity, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czech Republic; 2Biomedical Research Center, University Hospital Hradec Kralove, Hradec Kralove, Czech Republic; 3Department of Physical Electronics, Faculty of Nuclear Sciences and Physical Engineering, Czech Technical University in Prague, Prague, Czech Republic; 4Center for Advanced Functional Nanorobots, Department of Inorganic Chemistry, Faculty of Chemical Technology, University of Chemistry and Technology Prague, Prague, Czech Republic; 5Department of Chemistry, Faculty of Science, University of Hradec Kralove, Hradec Kralove, Czech Republic; 6Genome Integrity Unit, Danish Cancer Society Research Center, Copenhagen, Denmark; 7Department of Medical Biochemistry and Biophysics, Science for Life Laboratory, Division of Genome Biology, Karolinska Institute, Stockholm, SwedenCorrespondence: Monika ZarskaDepartment of Genome Integrity, Institute of Molecular Genetics of the Czech Academy of Sciences, Videnska 1083, Prague 4, Prague, CZ 142 20, Czech RepublicTel +420- 24106 3151Fax + 420-24106 2289Email monika.zarska@img.cas.czKamil KucaBiomedical Research Center, University Hospital Hradec Kralove, Sokolska 581, Hradec Kralove, CZ 500 05, Czech RepublicTel +420-495 833 447Email kamil.kuca@fnhk.czPurpose: Plasmonic photothermal cancer therapy by gold nanorods (GNRs) emerges as a promising tool for cancer treatment. The goal of this study was to design cationic oligoethylene glycol (OEG) compounds varying in hydrophobicity and molecular electrostatic potential as ligand shells of GNRs. Three series of ligands with different length of OEG chain (ethylene glycol units = 3, 4, 5) and variants of quaternary ammonium salts (QAS) as terminal functional group were synthesized and compared to a prototypical quaternary ammonium ligand with alkyl chain – (16-mercaptohexadecyl)trimethylammonium bromide (MTAB).Methods: Step-by-step research approach starting with the preparation of compounds characterized by NMR and HRMS spectra, GNRs ligand exchange evaluation through characterization of cytotoxicity and GNRs cellular uptake was used. A method quantifying the reshaping of GNRs was applied to determine the effect of ligand structure on the heat transport from GNRs under fs-laser irradiation.Results: Fourteen out of 18 synthesized OEG compounds successfully stabilized GNRs in the water. The colloidal stability of prepared GNRs in the cell culture medium decreased with the number of OEG units. In contrast, the cellular uptake of OEG+GNRs by HeLa cells increased with the length of OEG chain while the structure of the QAS group showed a minor role. Compared to MTAB, more hydrophilic OEG compounds exhibited nearly two order of magnitude lower cytotoxicity in free state and provided efficient cellular uptake of GNRs close to the level of MTAB. Regarding photothermal properties, OEG compounds evoked the photothermal reshaping of GNRs at lower peak fluence (14.8 mJ/cm2) of femtosecond laser irradiation than the alkanethiol MTAB.Conclusion: OEG+GNRs appear to be optimal for clinical applications with systemic administration of NPs not-requiring irradiation at high laser intensity such as drug delivery and photothermal therapy inducing apoptosis.Keywords: gold nanorods, quaternary ammonium salts, oligoethylene glycol, cellular uptake, photothermal stability

Solar water splitting using metal–insulator–semiconductor junctions has proven efficient, but these junctions degrade very rapidly. Here, the authors engineer metal–insulator–semiconductor interfaces in which Fermi-level pinning is reduced, producing an efficient and durable photoanode for solar-driven water oxidation.

A new method of clonal multiplication is described in a representative from the Cactaceae family, which offers wide experimental and horticultural applications. [ABSTRACT FROM AUTHOR]

Inhibition of cyclin-dependent kinases (CDKs) with small molecules has been suggested as a strategy for treatment of cancer, based on deregulation of CDKs commonly found in many types of human tumors. Here, a new potent CDK2 inhibitor with pyrazolo[4,3-d]pyrimidine scaffold has been synthesized, characterized, and evaluated in cellular and biochemical assays. 7-Benzylamino-5(R)-[2-(hydroxymethyl)propyl]amino-3-isopropyl-1(2)H-pyrazolo[4,3-d]pyrimidine, compound 7, was prepared as a bioisostere of the well-known CDK inhibitor roscovitine. An X-ray crystal structure of compound 7 bound to CDK2 has been determined, revealing a binding mode similar to that of roscovitine. Protein kinase selectivity profile of compound 7 and its biological effects (cell cycle arrest, dephosphorylation of the retinoblastoma protein, accumulation of the tumor suppressor protein p53, induction of apoptosis, inhibition of homologous recombination) are consistent with CDK inhibition as a primary mode of action. Importantly, as the anticancer activities of the pyrazolo[4,3-d]pyrimidine 7 exceed those of its bioisostere roscovitine, compound 7 reported here may be preferable for cancer therapy.

Intracellular levels of phosphorylation are regulated by the coordinated action of protein kinases and phosphatases. Disregulation of this balance can lead to cellular transformation. Here we review knowledge of the mechanisms of one protein phosphatase, the tumour suppressor PTEN/MMAC/TEP 1 apropos its role in tumorigenesis and signal transduction. PTEN plays an important role in the phosphatidyl-inositol-3-kinase (PI3-K) pathway by catalyzing degradation of phosphatidylinositol-(3,4,5)-triphosphate generated by PI3-K. This inhibits downstream targets mainly protein kinase B (PKB/Akt), cell survival and proliferation. PTEN contributes to cell cycle regulation by blockade of cells entering the S phase of the cell cycle, and by upregulation of p27(Kip1) which is recruited into the cyclin E/cdk2 complex. PTEN also modulates cell migration and motility by regulation of the extracellular signal-related kinase - mitogen activated protein kinase (ERK-MAPK) pathway and by dephosphorylation of focal adhesion kinase (FAK). We also emphasize the increasingly important role that PTEN has from an evolutionary point of view. A number of PTEN functions have been elucidated but more information is needed for utilization in clinical application and potential cancer therapy.

Testicular sperm extraction (TESE) was performed in 27 men in 30 cycles. All men were examined for genetics, serum hormonal status, biochemical status of semen samples. All men were examined by an urologist. No prognostic evaluation able to provide information about the prognosis of TESE procedure was found. Even a high FSH level, testicular hypotrophy or previous histological examination cannot exclude any patient from testicular biopsy.

Male infertility can be treated by several methods with varying degree of success. We present evidence that "open" testicular biopsy is favorable for men suffering from non-obstructive azoospermia (NOA). Moreover, any NOA patient may be subjected to this treatment even though his past histopathological examinations suggest that it is likely no sperm will be found in the testicular tissue. Thus, we recommend the testicular sperm extraction (TESE) procedure for NOA patients.

A ten-year experience with diagnosis and therapy of metabolic abnormalities and crystallization risks in patients with recurrent urolithiasis is presented. Since 1985, more than 900 persons with recurrent urolithiasis have been examined at the Metabolic Centre of the Hospital in Sternberk. The patients were examined routinely at ambulance or during hospitalization; the examination consisted of repeated urine and blood collections after the diet with various content of calcium and salt. All initial data (case history, physical finding, biochemistry, radiodiagnostics) were processed by a semi-expert computing program SOFT which was also used for monitoring of the therapy. Then the patients were divided into individual risk groups (Pak). Of all probands, the group of 130 patients (satisfying the strict criteria of the study) was selected and the data obtained was processed statistically. The group of 130 patients with recurrent urolithiasis (all of them were drug-treated) was compared to the group of 50 individuals with urolithiasis treated by diet and regimen measures. The patients given drugs showed a significantly increased crystallization inhibitors concentration in urine and reduced crystallization promotors, or relative saturation of some lithiatic substances. The paper analyzes the effect of the mostly administered drugs on crystallization risks and some less known "metabolic" indications of application of some drugs are recommended. It is concluded that the dietary, drinking and regime measures are basic for a good therapy of patients with urolithiasis, but patients with recurrent urolithiasis should be applied a selective metaphylaxis of drugs after routine metabolic examination. This finding is supported by a low number of recurrent urolithiasis.

The increase of organ transposition ill tile reconstruction of digestive tract, particularly transposition of the stomach and colon, is essential ill gullet surgery. The transposition is always accompanied by certain bigger or less degree of ischemia. In this study the authors followed the biochemical markers of tissue ischaemia, capable to lay down both pre- and postoperative vitality of the tucked organ an the anastomosis. Disclosing of the initial and later stadium of intestine ischemia is tile aim. Monitoring of the lactate in the serum is very useful. Its using was proved in the rich experimental group and it was certified in clinical practice.