Telomere and microtubule targeting in treatment-sensitive and treatment-resistant human prostate cancer cells

Modulating telomere dynamics may be a useful strategy for targeting prostate cancer cells, because they generally have short telomeres. Because a plateau has been reached in the development of taxane-based treatments for prostate cancer, this study was undertaken to evaluate the relative efficacy of targeting telomeres and microtubules in taxane-sensitive, taxane-resistant, androgen-sensitive, and androgen-insensitive prostate cancer cells. Paclitaxel- and docetaxel-resistant DU145 cells were developed and their underlying adaptive responses were evaluated. Telomere dynamics and the effects of targeting telomeres with sodium meta-arsenite (KML001) (an agent undergoing early clinical trials), including combinations with paclitaxel and docetaxel, were evaluated in parental and drug-resistant cells. The studies were extended to androgen-sensitive LNCaP cells and androgen-insensitive LNCaP/C81 cells. Both P-glycoprotein (Pgp)-dependent and non-Pgp-dependent mechanisms of resistance were recruited within the same population of DU145 cells with selection for drug resistance. Wild-type DU145 cells have a small side population (SP) (0.4-1.2%). The SP fraction increased with increasing drug resistance, which was correlated with enhanced expression of Pgp but not breast cancer resistance protein. Telomere dynamics remained unchanged in taxane-resistant cells, which retained sensitivity to KML001. Furthermore, KML001 targeted SP and non-SP fractions, inducing DNA damage signaling in both fractions. KML001 induced telomere erosion, decreased telomerase gene expression, and was highly synergistic with the taxanes in wild-type and drug-resistant DU145 cells. This synergism extended to androgen-sensitive and androgen-insensitive LNCaP cells under basal and androgen-deprived conditions. These studies demonstrate that KML001 plus docetaxel and KML001 plus paclitaxel represent highly synergistic drug combinations that should be explored further in the different disease states of prostate cancer.     

Achondroplasia: Craniofacial manifestations and considerations in dental management

Achondroplasia is the most common form of skeletal dysplasia dwarfism that manifests with stunted stature and disproportionate limb shortening. Achondroplasia is of dental interest because of its characteristic craniofacial features which include relative macrocephaly, depressed nasal bridge and maxillary hypoplasia. Presence of large head, implanted shunt, airway obstruction and difficulty in head control require special precautions during dental management. Craniofacial manifestations and considerations in dental management are presented in 11-year-old female patient with achondroplasia.Keyword: Achondroplasia, Craniofacial manifestations, Dental management     

Effect of Different Wax Pattern Manufacturing Techniques on the Marginal Fit of Lithium Disilicate Crowns

Purpose: The present study evaluated the marginal gap of lithium disilicate crowns fabricated through three different wax pattern techniques; Conventional, Milling and 3D-printing. Materials and Methods: Thirty stone models were replicated from a stainless-steel model representing a prepared tooth; ten were sent to make conventional wax patterns while the remaining were sent to a digital dental scanner. The computer aided design was completed and STL (Standard Tessellation Language) files were sent to either milling or 3D-printing machines. All wax patterns (n = 30) were pressed, and a stabilizing instrument was used to secure the crowns on the master model. The marginal gap was measured at 18 points for each crown using a digital microscope (µm) (n = 540) and compared using One-way ANOVA (p ≤ 0.05). Results: There was a significant difference in the marginal gap value between all three groups (p < 0.01) where the milled group showed the least mean gap (28.87 ± 30.18 µm), followed by 3D printed (47.85 ± 27.44 µm), while the highest mean marginal gap was found in the conventional group (63.49 ± 28.05 µm). Conclusion: Milled and 3D-printed wax patterns produced better fitting crowns compared to conventional techniques.     

Investigating the Microstructural and Mechanical Properties of Novel Ternary Reinforced AA7075 Hybrid Metal Matrix Composite

This study investigates the comparison of the microstructural and mechanical properties of a novel ternary reinforced AA7075 hybrid metal matrix composite. Four samples, including AA7075 (base alloy), AA7075-5wt %SiC (MMC), AA7075-5wt %SiC-3wt %RHA (s-HMMC), and AA7075-5wt %SiC-3wt %RHA-1wt %CES (n-HMMC) were developed using the stir casting liquid metallurgy route, followed by the heat treatment. The experimental densities corresponded with the theoretical values, confirming the successful fabrication of the samples. A minimum density of 2714 kg/m³ was recorded for the n-HMMC. In addition, the highest porosity of 3.11% was found for n-HMMC. Furthermore, an increase of 24.4% in ultimate tensile strength and 32.8% in hardness of the n-HMMC was recorded compared to the base alloy. However, its ductility and impact strength was compromised with the lower values of 5.98% and 1.5 J, respectively. This was confirmed by microstructural analysis, which reveals that n-HMMC has mixing issues and forms agglomerates in the matrix, which served as the potential sites of stress concentration leading to low impact strength and ductility. Nevertheless, the hybrid composites showed superior mechanical properties over the MMC and its base alloy.     

Multidisciplinary management of congenitally missing lateral incisors: A minimally invasive approach

The following case report demonstrates how a multidisciplinary team approach can be utilized successfully for the minimally invasive esthetic treatment of congenitally missing maxillary lateral incisors through space closure and canine re‐anatomization.     

A novel biallelic variant in the Popeye domain-containing protein 1 (POPDC1) underlies limb girdle muscle dystrophy type 25

POPDC1 also known as BVES, is a highly conserved transmembrane protein, important for striated muscle function and homeostasis. Pathogenic variants in the POPDC1 gene are associated with limb-girdle muscular dystrophy type 25 (LGMDR25). In the present study, we performed trio-whole exome sequencing (WES) followed by Sanger sequencing on a single family having LGMD clinical features. Protein modeling of all POPDC1 missense variants (POPDC1^Pro134Leu, POPDC1^Ile193Ser, and POPDC1^Ser201Phe) associated with LGMDR25 were performed using Molecular Dynamics (MD) simulation. We identified a homozygous missense variant (c.401C>T; p.Pro134Leu) in the POPDC1 gene. Altered 3D structure, disruptive fluctuation, less compactness, and instability were observed in all the three variants of POPDC1 protein models. In comparison, POPDC1^Ser201Phe protein dynamics were more unstable than other variants. Functional study of newly identified variant would add key answers to underlying mechanisms of the disease.