Hospital-based Survey on Knowledge and Attitude Toward Colorectal Cancer Screening Among Indonesian Population

Background: Several western countries have recommended colorectal cancer (CRC) screening, however the yield of CRC screening is still low. The acceptability of CRC screening is influenced by people\u27s knowledge and attitude. This study was conducted to evaluate the knowledge and attitude of Indonesian people toward CRC screening. Method: Adult Indonesian population aged 19–65 years was recruited in this hospital-based survey. Knowledge and attitude toward CRC screening were assessed by using structured questionnaires consisting of nine chapters. Result: There were 614 respondents recruited in this study. Most respondents (36.2%) incorrectly pointed out abdominal pain or pain around anus as the symptom of bowel cancer. Regarding CRC risk factors, eating fruits or vegetables rarely was the most frequent answer (28.5%) encountered. Only one-third (28%) of respondents mentioned colonoscopy as the Method for CRC screening. There were 38.1% of respondents who believed that CRC screening test might be harmful to the body. Up to 70.8% of the respondents agreed and strongly agreed that CRC screening test might cause physical discomfort. Two fifth (41.5%) of respondents believed that CRC screening test was embarrassing. More than half (58.8%) of respondents were afraid of having the CRC screening test. The test was too expensive according to 79.5% of respondents. Conclusion: The knowledge on CRC symptoms, risk factors, and screening tests is still low among Indonesian population. Our study result indicates that the lack of knowledge and the discouraging attitude among Indonesian population will be the major barriers to implement CRC screening in Indonesia

Synthesis, characterisation and antibacterial activity of Schiff base derived from S-methyldithiocarbazate and methylisatin.

New tridentate nitrogen–oxygen–sulfur Schiff base has been prepared from the condensation reaction of S-methyldithiocarbazate and methylisatin. The compound crystallized in triclinic crystal system with space group P − 1, Z = 2, V = 612.92(3) Å3 and unit cell parameters a = 6.8540(2) Å, b = 8.3022(2) Å, c = 11.5243(4) Å, α = 79.8186(13)°, β = 90.5224(14)° and γ = 72.1362(13)°. Crystal structure reveals that the compound exists in the thione form with the methylisatin moiety is trans with respect to the C3–N2 and C3–S4 bonds whereas the methyl group of the dithiocarbazate moiety is cis with respect to the C3–N2 and C3–S5 bonds. The Schiff base was found to be selectively active against the selected Gram positive bacterial strains (Bacillus subtilis and Staphylococcus aureus) with the inhibition zones of 16 and 12 mm, respectively

The crystal structure and cytotoxicity of centrosymmetric copper(II) complex derived from S-methyldithiocarbazate with isatin.

Copper(II) complex of S-methyldithiocarbazate with isatin has been prepared and screened for their cytotoxic activities against MCF-7 (Human non-metastatic mammary gland adenocarcinoma cell line) and MDA-MB-231 (Human metastatic mammary gland adenocarcinoma cell line). The compound crystallized in an orthorhombic crystal system with a space group C 2cb and was found to be selectively active against MCF-7 cell line (Human non-metastatic mammary gland adenocarcinoma cell line with an IC50 value 0.45 μg/mL. The crystal structure of this centrosymmetric Cu(SMISA)2 complex (SMISA = Schiff base formed by condensation reaction of S-methyldithiocarbazate with isatin) showed that the copper atom has a distorted square-planar geometry with the Schiff base coordinated to the metal ion as a uninegatively charged bidentate ligand through the azomethine nitrogen and thiolate sulfur

Synthesis, characterization and cytotoxic activity of S-benzyldithiocarbazate Schiff bases derived from 5-fluoroisatin, 5-chloroisatin, 5-bromoisatin and their crystal structures

Schiff bases were prepared from S-benzyldithiocarbazate with 5-fluro-, 5-chloro- and 5-bromoisatin. All are potential tridentate nitrogen, oxygen, sulfur donors. They were found to be selectively active against MCF-7 cell line (Human non-metastatic mammary gland adenocarcinoma cell line). The bromide and fluoride compounds were the most active with IC50 values of 6.40 μM (2.6 μg/mL) and 9.26 μM (3.2 μg/mL) respectively while the chloride derivative was weakly active with an IC50 value of 38.69 μM (14.0 μg/mL). The cytotoxic activity of the halo substituted isatins against the breast cancer cell lines tested is in the order of Br > F > Cl. Planarity of the isatin ring in the Schiff bases can be arranged in the following order SB5FISA > SB5ClISA > SB5BrISA while the perpendicularity of the benzyl ring towards the dithiocarbazate plane can be ordered as follows, SB5FISA > SB5BrISA > SB5ClISA

Binding of an RNA trafficking response element to heterogeneous nuclear ribonucleoproteins A1 and A2

Heterogeneous nuclear ribonucleoprotein (hnRNP) A2 binds a 21-nucleotide myelin basic protein mRNA response element, the A2RE, and A2RE-like sequences in other localized mRNAs, and is a trans-acting factor in oligodendrocyte cytoplasmic RNA trafficking. Recombinant human hnRNPs A1 and A2 were used in a biosensor to explore interactions with A2RE and the cognate oligodeoxyribonucleotide. Both proteins have a single site that bound oligonucleotides with markedly different sequences but did not bind in the presence of heparin. Both also possess a second, specific site that bound only A2RE and was unaffected by heparin, hnRNP A2 bound A2RE in the latter site with a K-d near 50 nM, whereas the K-d for hnRNP A1 was above 10 muM. UV cross-linking assays led to a similar conclusion. Mutant A2RE sequences, that in earlier qualitative studies appeared not to bind hnRNP A2 or support RNA trafficking in oligodendrocytes, had dissociation constants above 5 muM for this protein. The two concatenated RNA recognition motifs (RRMs), but not the individual RRMs, mimicked the binding behavior of hnRNP A2. These data highlight the specificity of the interaction of A2RE with these hnRNPs and suggest that the sequence-specific A2RE-binding site on hnRNP A2 is formed by both RRMs acting in cis

Phosphorothioate antisense oligonucleotides induce the formation of nuclear bodies

Antisense oligonucleotides are powerful tools for the in vivo regulation of gene expression. We have characterized the intracellular distribution of fluorescently tagged phosphorothioate oligodeoxynucleotides (PS-ONs) at high resolution under conditions in which PS-ONs have the potential to display antisense activity. Under these conditions PS-ONs predominantly localized to the cell nucleus where they accumulated in 20-30 bright spherical foci designated phosphorothioate bodies (PS bodies), which were set against a diffuse nucleoplasmic population excluding nucleoli. PS bodies are nuclear structures that formed in cells after PS-ON delivery by transfection agents or microinjection but were observed irrespectively of antisense activity or sequence. Ultrastructurally, PS bodies corresponded to electron-dense structures of 150-300 nm diameter and resembled nuclear bodies that were found with lower frequency in cells lacking PS-ONs. The environment of a living cell was required for the de novo formation of PS bodies, which occurred within minutes after the introduction of PS-ONs. PS bodies were stable entities that underwent noticeable reorganization only during mitosis. Upon exit from mitosis, PS bodies were assembled de novo from diffuse PS-ON pools in the daughter nuclei. In situ fractionation demonstrated an association of PS-ONs with the nuclear matrix. Taken together, our data provide evidence for the formation of a nuclear body in cells after introduction of phosphorothioate oligodeoxynucleotides

Prediction of Protein Binding Regions in Disordered Proteins

Many disordered proteins function via binding to a structured partner and undergo a disorder-to-order transition. The coupled folding and binding can confer several functional advantages such as the precise control of binding specificity without increased affinity. Additionally, the inherent flexibility allows the binding site to adopt various conformations and to bind to multiple partners. These features explain the prevalence of such binding elements in signaling and regulatory processes. In this work, we report ANCHOR, a method for the prediction of disordered binding regions. ANCHOR relies on the pairwise energy estimation approach that is the basis of IUPred, a previous general disorder prediction method. In order to predict disordered binding regions, we seek to identify segments that are in disordered regions, cannot form enough favorable intrachain interactions to fold on their own, and are likely to gain stabilizing energy by interacting with a globular protein partner. The performance of ANCHOR was found to be largely independent from the amino acid composition and adopted secondary structure. Longer binding sites generally were predicted to be segmented, in agreement with available experimentally characterized examples. Scanning several hundred proteomes showed that the occurrence of disordered binding sites increased with the complexity of the organisms even compared to disordered regions in general. Furthermore, the length distribution of binding sites was different from disordered protein regions in general and was dominated by shorter segments. These results underline the importance of disordered proteins and protein segments in establishing new binding regions. Due to their specific biophysical properties, disordered binding sites generally carry a robust sequence signal, and this signal is efficiently captured by our method. Through its generality, ANCHOR opens new ways to study the essential functional sites of disordered proteins

Cytoskeletal control of B cell responses to antigens.

The actin cytoskeleton is essential for cell mechanics and has increasingly been implicated in the regulation of cell signalling. In B cells, the actin cytoskeleton is extensively coupled to B cell receptor (BCR) signalling pathways, and defects of the actin cytoskeleton can either promote or suppress B cell activation. Recent insights from studies using single-cell imaging and biophysical techniques suggest that actin orchestrates BCR signalling at the plasma membrane through effects on protein diffusion and that it regulates antigen discrimination through the biomechanics of immune synapses. These mechanical functions also have a role in the adaptation of B cell subsets to specialized tasks during antibody responses