In Silico and In Vitro Analysis of Tacca Tubers (Tacca leontopetaloides) from Banyak Island, Aceh Singkil Regency, Indonesia, as Antihypercholesterolemia Agents.

Tacca leontopetaloides (T. leontopetaloides) contain a number of active compounds such as flavonoids, tannins, phenolics, steroids, and alkaloids. The active compounds from plants have been shown to reduce the risk of cardiovascular disease by lowering cholesterol levels by inhibiting the enzyme 3-hydroxy-3-methylglutaryl-coenzym A (HMG-CoA) reductase activity. This study aims to investigate the potential active compounds in the ethanolic extract of Tacca tubers (T. leontopetaloides) from the Banyak Islands, Aceh Singkil Regency, Aceh Province both in vitro and in silico. Tacca tubers contain secondary metabolites including flavonoids, phenolics, tannins, steroids and saponins, according to phytochemical screening. In vitro investigation of ethanolic extract of Tacca tuber revealed inhibitory activity of HMG Co-A reductase with an IC50 value of 4.92 ppm. Based on the in silico study, active compound from the extract, namely Stigmasterol with the highest binding affinities with HMG Co-A reductase (-7.2 kcal/mol). As a comparison, the inhibition of HMG Co-A reductase activity by simvastatin with an IC50 4.62 ppm and binding affinity -8.0 Kcal/mol. Our findings suggest that the ethanolic extract of Tacca tuber (T. leontopetaloides) from Banyak Islands, Aceh Province has the potential to inhibit the activity of HMG Co-A reductase.

Clinical Utility of BRAF, NRAS, and TERT Promoter Mutation in Preoperative Thyroid Fine-Needle Aspiration Biopsy: A Diagnostic Study From Dharmais Cancer Hospital.

OBJECTIVE: Molecular testing of thyroid nodules becomes important for improving the accuracy of fine-needle aspiration biopsy (FNAB). This study aimed to investigate the diagnostic utility of BRAF, NRAS, and TERT promoter mutation in thyroid nodules at Dharmais Cancer Hospital.
Methods: We performed a prospective diagnostic study involving 50 patients with thyroid nodules who needed surgery between September 2013 and August 2014. Mutational hotspots in BRAF exon 15, NRAS exon 3, and TERT promoter region were analyzed by Sanger sequencing from FNAB specimens. Cytology and molecular data were compared to histopathology results.
Result: Of the 50 cases included in the analysis, 39 cases (78%) were thyroid malignancies. Mutations of BRAF, NRAS, and TERT promoter were detected in 31% (12/39), 18% (7/39), and 13% (5/39) cases, respectively. BRAF and NRAS mutations were found mutually exclusive, while all of TERT promoter mutation was found coexistent either with BRAF (40%) or NRAS (60%). The combination of FNAB cytology and molecular testing resulted in 69% sensitivity, 100% specificity, 100% positive predictive value, 48% negative predictive value, and 76% accuracy.
Conclusion: Molecular testing of BRAF, NRAS, and TERT mutations improve the sensitivity of thyroid FNAB and is beneficial for more definitive treatment in selective cases. However, the NPV is relatively low to avoid the need for diagnostic surgery. Therefore, further studies to identify more sensitive methods and more comprehensive molecular markers in the diagnosis of thyroid nodules are needed.

Inclusion Complexes Between Polytetrahydrofuran-b-Amylose Block Copolymers and Polytetrahydrofuran Chains.

Amylose inclusion complexes are prepared by complexation of synthetic amylose having a covalently attached PTHF block (PTHF-b-amylose) with guest polytetrahydrofuran of molecular weights of 650 and 1000 g · mol(-1) (PTHF650 and PTHF1000). Differential Scanning Calorimetry (DSC) analysis of the products shows a characteristic melting peak of the complexes at 140 °C. Compared to PTHF650, the PTHF1000 displays lower complexing ability with PTHF-b-amylose which is indicated by visible amylose retrogradation. The possible structures of the resulting products are estimated from Thermo Gravimetric Analysis (TGA) which reveals differences between PTHF-b-amylose and the corresponding complexes. In addition, X-Ray Diffraction (XRD) analysis demonstrates that the resulting structures of the complexes consist of 6-fold V-amylose helices. The results are confirmed further with Small Angle X-Ray Scattering (SAXS) diffractions which show that formation of inclusion complexes increases the crystalline size and regularity of the complex. There is a strong indication that the covalently attached PTHF block also induces the formation of V-amylose by residing in between the amylose blocks. In this case, the resulting structure of the complex is likely affected by both the complexation between amylose block and the added PTHF and by the in situ self-assembly of the block copolymers.

Solvent-responsive behavior of inclusion complexes between amylose and polytetrahydrofuran.

Highly crystalline amylose-polytetrahydrofuran (PTHF) complexes can be obtained by employing organic solvents as washing agents after complex formation. The X-ray diffraction (XRD) of the washed complexes appear sharp at 12.9°-13.2° and 19.6°-20.1°, clear signs of the presence of V6I -amylose. Other diffraction peaks correlate with V6II -amylose, which indicates that the complexed amylose helices are in the form of an intermediate or a mixture of V6I - and V6II -amylose. SEM imaging reveals that the amylose-PTHF complexes crystallize in the form of lamellae, which aggregate in a round shape on top of one another with a diameter around 4-8 µm. Some lamellas aggregate as flower-like or flat-surface spherulitic crystals. There is a visible matrix in between the aggregated lamellas which shows that a part of the amylose-PTHF complexes is amorphous.

Tunable properties of inclusion complexes between amylose and polytetrahydrofuran.

Amylose and polytetrahydrofuran (PTHF) are mixed in an aqueous solution to form inclusion complexes. DSC shows that immediate mixing results in complexes having lower melting temperatures compared with complexes prepared with longer mixing times. The washed complexes melt at higher temperatures compared with the corresponding unwashed complexes. XRD indicates that amylose-PTHF complexes diffract similar to amylose-fatty acids complexes (V6I -amylose helices), with additional diffractions correlating with amylose-alcohol complexes (V6II -amylose helices). This suggests that the structure of amylose-PTHF complexes is an intermediate or a mixture between V6I - and V6II -amylose. This shows that, besides residing inside the amylose helices, some PTHF chains are located in between the amylose helices.

Facile preparation method for inclusion complexes between amylose and polytetrahydrofurans.

Several methods were used to investigate the possibility of preparing inclusion complexes between amylose and polytetrahydrofurans (PTHF) via direct mixing. Potato amylose (M(v) ∼ 200 kg/mol) and synthetic amylose (M(n) 42 kg/mol) were complexed with PTHF having different molecular weights (M(n) between 650 and 2900 g/mol) to study the effect of the length of the host and the guest molecules on the complexation. The resulted products were studied by differential scanning calorimetry (DSC) that showed a characteristic melting peak in the range of 120-140 °C. Emulsification of both amylose and polytetrahydrofuran improved the complexation. The largest amount of complexes was obtained with shorter PTHF chains, which also resulted in less amylose retrogradation. Furthermore, PTHF chains with similar molecular weight but different end groups were used. Amine terminated PTHF formed a higher amount of complexes compared to the hydroxyl terminated PTHF. However, no amylose complexes were formed using benzoyl terminated PTHF with low molecular weight. This is due to the bulky group of benzoyl, which indicates that the mechanism of the complexation between amylose and PTHF occurs via insertion rather than wrapping. In addition, X-ray diffraction (XRD) analysis showed that the included PTHFs induced the formation of the so-called V-amylose with six glucose residues per helix turn. Some additional diffraction peaks indicate that the induced V(6)-amylose is probably an intermediate or the mixtures between V(6I)- and V(6II)-amylose.