Epigenetic Connection of the Calcitonin Gene-Related Peptide and Its Potential in Migraine.

The calcitonin gene-related peptide (CGRP) is implicated in the pathogenesis of several pain-related syndromes, including migraine. Targeting CGRP and its receptor by their antagonists and antibodies was a breakthrough in migraine therapy, but the need to improve efficacy and limit the side effects of these drugs justify further studies on the regulation of CGRP in migraine. The expression of the CGRP encoding gene, , is modulated by epigenetic modifications, including the DNA methylation, histone modification, and effects of micro RNAs (miRNAs), circular RNAs, and long-coding RNAs (lncRNAs).

RIF1 Links Replication Timing with Fork Reactivation and DNA Double-Strand Break Repair.

Replication timing (RT) is a cellular program to coordinate initiation of DNA replication in all origins within the genome. RIF1 (replication timing regulatory factor 1) is a master regulator of RT in human cells. This role of RIF1 is associated with binding G4-quadruplexes and changes in 3D chromatin that may suppress origin activation over a long distance.

Development of immediate release 3D-printed dosage forms for a poorly water-soluble drug by fused deposition modeling: Study of morphology, solid state and dissolution.

3D-printing technologies such as Fused Deposition Modeling (FDM) bring a unique opportunity for personalized and flexible near-patient production of pharmaceuticals, potentially improving safety and efficacy for some medications. However, FDM-printed tablets often exhibit tendency for slow dissolution due to polymer erosion-based dissolution mechanisms. Development of immediate release (IR) 3D-printed dosage with poorly water-soluble compounds is even more challenging but necessary to ensure wide applicability of the technology within pharmaceutical development portfolios.

The Aging Stress Response and Its Implication for AMD Pathogenesis.

Aging induces several stress response pathways to counterbalance detrimental changes associated with this process. These pathways include nutrient signaling, proteostasis, mitochondrial quality control and DNA damage response. At the cellular level, these pathways are controlled by evolutionarily conserved signaling molecules, such as 5'AMP-activated protein kinase (AMPK), mechanistic target of rapamycin (mTOR), insulin/insulin-like growth factor 1 (IGF-1) and sirtuins, including SIRT1.

An Indirect Synthetic Approach toward Conformationally Constrained 20-Membered Unclosed Cryptands via Late-Stage Installation of Intraannular Substituents.

A new protocol for PTC-mediated O-alkylation of the intraannular position of 20-membered unclosed cryptands (UCs) is reported. In contrast to the classical, "direct" strategy, which requires functionalization of the lariat arm at the beginning of synthesis, this "indirect" approach enables the late-stage introduction of various benzylic substituents after an unfavorable macrocyclization step (11 examples, yields up to 98%). Notably, this method permits preparation of, previously inaccessible, crowded UCs bearing 1-acetylpyrene substituent and dimer joined by p-xylene linker.

New classification system of endometrial hyperplasia WHO 2014 and its clinical implications.

Endometrial hyperplasia (EH) is a pathological condition characterised by hyperplastic changes in endometrial glandular and stromal structures lining the uterine cavity. Endometrial hyperplasia, particularly with atypia, is a significant clinical concern because it can be a precursor of endometrial cancer. Accurate diagnosis of precancerous lesions of the endometrium and exclusion of coexisting endometrial carcinomas are absolutely required for the optimal management of patients.

Photochromic Torsional Switch (PTS): a light-driven actuator for the dynamic tuning of π-conjugation extension.

Here we present a molecular architecture that can reversibly change the geometric conformation of its π-system backbone irradiation with two different wavelengths. The proposed 'molecular actuator' consists of a photoswitchable azobenzene orthogonally connected to a π-conjugated bithiophene by both direct and aliphatic linker-assisted bonding. Upon exposure to 350 nm light, the azobenzene moiety isomerizes to its form, causing the bithiophene to assume a semiplanar anti conformation (extended π-conjugation).

Polymorphism of DNA mismatch repair genes in endometrial cancer.

Unlabelled: Endometrial cancer (EC) is the second most common malignancy associated with hereditary non-polyposis colorectal cancer (HNPCC) family. The development of HNPCC is associated with defects in DNA mismatch repair (MMR) pathway resulting in microsatellite instability (MSI). MSI is present in a greater number of EC than can be accounted for by inherited MMR mutations, therefore alternative mechanisms may underline defective MMR in EC, including polymorphic variation.

[Evaluation of genomic imbalance in endometrial hyperplasia and carcinoma].

Objective: The main goal of our study was to identify the earliest and specific genetic changes which could be associated with an increased risk of neoplastic transformation in a group of patients with endometrial hyperplasia. Another goal was to characterize genetic changes associated with advanced forms of cancer.

Material And Methods: The study involved forty-four (44) female patients, including five (5) patients with no histopathologically confirmed hyperplastic features, twenty-six (26) patients with histopathologically confirmed endometrial hyperplasia, and thirteen (13) patients with diagnosed carcinoma of the endometrium.

Self-organizing surface-initiated polymerization, templated self-sorting and templated stack exchange: synthetic methods to build complex systems.

In nature, spectacular function is achieved by highly sophisticated supramolecular architectures. Little is known what we would obtain if we could create complexity with similar precision, because the synthetic methods to do so are not available. This account summarizes recent approaches conceived to improve on this situation.

Polymorphisms of DNA repair genes in endometrial cancer.

Endometrial cancer belongs to the commonest malignancy in females. Its development may be associated with the high exposure of endometrium to exo- and endogenous estrogens. Estrogens produce DNA bulky adducts and oxidative base damages which are removed in nucleotide excision repair (NER) and base excision repair (BER) pathways.

Creation of chiral thixotropic gels through a crown-ammonium interaction and their application to a memory-erasing recycle system.

A unique class of oligothiophene-based organogelator bearing two crown ethers at both ends was synthesized. This compound could gelatinize several organic solvents, forming one-dimensional fibrous aggregates. From the observation of circular dichroism, it was confirmed that the helical handedness of the fibrous assembly is controllable by the chirality of 1,2-bisammonium guests, thus suggesting that one guest molecule bridges two gelator molecules through the crown-ammonium interaction.

Differential involvement of mGluR1 and mGluR5 in memory reconsolidation and retrieval in a passive avoidance task in 1-day old chicks.

Group I metabotropic glutamate receptors (mGluRs) are involved in memory formation. The Ca2+ signal derived from stimulation of IP3 receptors (IP3Rs) via mGluRs, initiates protein synthesis that is required for memory consolidation and reconsolidation. However it has been suggested that different mechanisms are triggered by mGluR1/5 activation in these two processes.

Study of host-guest interactions in benzodiazacoronands by means of solid state NMR spectroscopy, X-ray diffraction and quantum mechanical computations.

In this work we present solid state data for five host-guest complexes formed by N-(4,19-dioxo-2,8,15,21-tetraoxa-5,18-diazatricyclohexacosa-1(25),9(14),10,12,22(26),23-hexaen-26-yl)-benzamide (1) belonging to the group of benzodiazacoronands, achiral compounds for which chiral crystals were found (J. Kalisiak and J. Jurczak, Cryst.

New strategy for controlling the oligothiophene aggregation mode utilizing the gel-to-sol phase transition induced by crown-alkali metal interactions.

A new functional low molecular-weight gelator (LMWG) based on crown-appended quaterthiophene was synthesized and investigated as a new alkali metal cation responsive material with enhanced fluorescence emission upon gel-to-sol phase transition.

DNA damage and repair in endometrial cancer in correlation with the hOGG1 and RAD51 genes polymorphism.

The cellular reaction to the DNA-damaging agents may modulate individual's cancer susceptibility. This reaction is mainly determined by the efficacy of DNA repair, which in turn, may be influenced by the variability of DNA repair genes, expressed by their polymorphism. The hOGG1 gene encodes a glycosylase of base excision repair and RAD51 specifies a key protein in homologues recombination repair.

Analysis of the polymorphisms in non-homologous DNA end joining (NHEJ) gene Ku70 and Ligase IV in sporadic breast cancer in women.

Purpose: Breast cancer is one of the major killers worldwide. Aberrant double-stranded break (DSB) repair leads to genomic instability, which is a hallmark of malignant cells. Double-stranded breaks are repaired in two pathways: homologous recombination (HR) and non-homologous DNA end joining (NHEJ).

Polymorphism of the ERalpha and CYP1B1 genes in endometrial cancer in a Polish subpopulation.

Aim: Metabolic activation of estrogens may play a role in endometrial carcinogenesis; and polymorphism of the genes (whose product is involved in this process) may be associated with the modulation of the risk of endometrial cancer. CYP1B1 plays a major role in the metabolism of estrogens, which must firstly bind their receptors, estrogen receptor alpha (ERalpha) or ER beta. In the present study we investigated the association of two polymorphisms of the CYP1B1 gene (Arg48Gly [142C > G] and Leu432Val [4326C > G]) and a polymorphism of the ERalpha gene (975C > G) as well as a combination between them with endometrial cancer occurrence.

The CYP17 and CYP19 gene single nucleotide polymorphism in women with sporadic breast cancer.

The cytochrome P450 family (CYPs) enzymes play an important role in the metabolism of environmental carcinogens and of oestrogen and can affect breast cancer risk. We hypothesise that polymorphisms of CYP17 and CYP19 gene can predict higher incidence of breast cancer. In the present work the distribution of genotypes and frequency of alleles of the T/C polymorphism in promoter region of CYP17 and Trp/Arg polymorphism in codon 39 of CYP19 gene in breast cancer women were investigated.

XRCC1 and XRCC3 DNA repair gene polymorphisms in breast cancer women from the Lodz region of Poland.

Aim: Genetic polymorphism in XRCC1 and XRCC3 genes may influence DNA repair capacity and, in turn, confer predisposition to breast cancer.

Material And Methods: In the present work the distribution of genotypes and frequency of alleles of the Arg194Trp and Arg399Gln polymorphism of XRCC1 and Trp241 Met polymorphism in XRCC3 in breast cancer women were analysed. Blood samples were obtained from 150 women with breast cancer and controls (n = 106).

Estrogen receptor alpha (ER-alpha) gene polymorphism in patients from the Lodz region of Poland with sporadic endometrial cancer.

Objective: Estrogens play a crucial role in the pathogenesis and progression of endometrial cancer. The gene ER-alpha is polymorphic and gene variability could contribute to the level of protein biosynthesis.

Methods: The aim of this study was to evaluate PvuII and XbaI polymorphism of the ER-alpha gene in 120 postmenopausal women with endometrial cancer in DNA samples obtained from cancer tissue.

Polymorphism of the homologous recombination repair genes RAD51 and XRCC3 in breast cancer.

The RAD51 protein and its paralog, XRCC3, play an important role in the repair of DNA double-strand breaks (DSBs) by homologous recombination. Since DSBs may contribute to the pathogenesis of breast cancer and variability in DNA repair genes may be linked with some cancers, we performed a case-control study (135 cases and 175 controls) to check the association between the genotypes of the Thr241Met polymorphism of the XRCC3 gene and the 135G>C polymorphism of the RAD51 gene and breast cancer occurrence and progression. Genotypes were determined in peripheral blood lymphocytes by RFLP-PCR.

[The analysis of estrogen receptor alpha (ER-alpha) gene Pvull and Xbal polymorphisms in postmenopausal women with breast cancer].

Unlabelled: Estrogens play a crucial role in the pathogenesis and progression of breast and endometrial cancer. The gene ER-alpha is polymorphic and gene variability could contribute to the level of protein biosynthesis. In the present work the distribution of genotypes and frequency of alleles of the Pvull polymorphism and Xbal polymorphism of ER-alpha gene in subjects with breast cancer were investigated.