Exploration of stilbenoid trimers as potential inhibitors of sirtuin1 enzyme using a molecular docking and molecular dynamics simulation approach

A combination of molecular docking and molecular dynamics simulation (250 ns) has been carried out to study the interaction of stilbenoid trimer compounds with the SIRT1 enzyme as the target protein. SIRT1 expression regulates cellular stress responses that lead to the development of cancer. Redocking showed a good native ligand pose with an RMSD value of 1.40 Å at the receptor active site''s coordinates. The molecular docking score uses a grid score functional (kcal mol⁻¹), which shows results of 1NS: 79.56, TS1: −26.83, TS2: −87.77, and TS3: −83.67. The TS2 and TS3 candidates were chosen for further analysis because they had a lower grid score than the native ligand (1NS). Furthermore, prediction of binding free energy (kcal mol⁻¹) using the Quantum Mechanics/generalized Born Surface Area (QM/MM-GBSA) method shows the results of 1NS: −31.52 ± 0.39, TS2: −58.99 ± 0.34, and TS3: −43.38 ± 0.35. These results indicate that the TS2 and TS3 compounds have good potential as inhibitors of the SIRT1 enzyme. Additionally, the amino acid residues were responsible for the inhibition mechanism through hydrogen bond interactions at the molecular level, including ASP22, PHE91, PRO11, ILE165, ASP166, and VAL230. The observations made in this study provide theoretical information for exploring the stilbenoid trimers as anticancer agents by targeting the SIRT1 enzyme.

A combination of molecular docking and molecular dynamics simulation (250 ns) has been carried out to study the interaction of stilbenoid trimer compounds with the SIRT1 enzyme as the target protein.     

Recent advances in biological nanopores for nanopore sequencing,sensing and comparison of functional variations in MspA mutants

Biological nanopores are revolutionizing human health by the great myriad of detection and diagnostic skills. Their nano-confined area and ingenious shape are suitable to investigate a diverse range of molecules that were difficult to identify with the previous techniques. Additionally, high throughput and label-free detection of target analytes instigated the exploration of new bacterial channel proteins such as Fragaceatoxin C (FraC), Cytolysin A (ClyA), Ferric hydroxamate uptake component A (FhuA) and Curli specific gene G (CsgG) along with the former ones, like α-hemolysin (αHL), Mycobacterium smegmatis porin A (MspA), aerolysin, bacteriophage phi 29 and Outer membrane porin G (OmpG). Herein, we discuss some well-known biological nanopores but emphasize on MspA and compare the effects of site-directed mutagenesis on the detection ability of its mutants in view of the surface charge distribution, voltage threshold and pore–analyte interaction. We also discuss illustrious and latest advances in biological nanopores for past 2–3 years due to limited space. Last but not the least, we elucidate our perspective for selecting a biological nanopore and propose some future directions to design a customized nanopore that would be suitable for DNA sequencing and sensing of other nontrivial molecules in question.

Future of nanopore DNA sequencing: schematic illustration shows the future of nanopore DNA sequencing by using a customized biological nanopore with appropriate fabrication.     

Designing a novel visible-light-driven heterostructure Ni–ZnO/S-g-C3N4 photocatalyst for coloured pollutant degradation

In this study, photocorrosion of ZnO is inhibited by doping Ni in the ZnO nanostructure and electron–hole recombination was solved by forming a heterostructure with S-g-C₃N₄. Ni is doped into ZnO NPs from 0 to 10% (w/w). Among the Ni-decorated ZnO NPs, 4% Ni-doped ZnO NPs (4NZO) showed the best performance. So, 4% Ni–ZnO was used to form heterostructure NCs with S-g-C₃N₄. NZO NPs were formed by the wet co-precipitation route by varying the weight percentage of Ni (0–10% w/w). Methylene blue (MB) was used as a model dye for photocatalytic studies. For the preparation of the 4NZO-x-SCN nanocomposite, 4NZO NPs were formed in situ in the presence of various concentrations of S-g-C₃N₄ (10–50% (w/w)) by using the coprecipitation route. The electron spin resonance (ESR) and radical scavenger studies showed that O₂⁻ and OH free radicals were the main reactive species that were responsible for MB photodegradation.

Ni-doped ZnO/S-g-C₃N₄ nanocomposites were formed as a novel heterostructure photocatalyst.     

Acute epiploic appendagitis mimicking symptoms of urinary tract infection: A diagnostic enigma in the emergency department

The epiploic appendages (also known as appendices epiploicae) are usually located on the anti‐mesenteric surface of the colon, extending from the caecum to the rectosigmoid, and epiploic appendagitis (EA) is the inflammation of these appendages. We report a clinical image of epiploic appendagitis creating a diagnostic challenge.     

Microbubble drug conjugate and focused ultrasound blood brain barrier delivery of AAV-2 SIRT-3

BackgroundDelivery of viral vectors as gene therapies to treat neurodegenerative diseases has been hampered by the inability to penetrate the blood brain barrier (BBB) and invasive or non-targeted delivery options prone to inducing immune responses. MR guided focused ultrasound (MR-g-FUS) and microbubbles have demonstrated safe, temporary, targeted BBB permeabilization clinically.MethodsWe developed clinically scalable, microbubble drug conjugates (MDCs) for the viral gene therapy, AAV.SIRT3-myc [adeno-associated virus expressing myc-tagged SIRT3], which has previously been shown to have disease modifying effects in animal models of Parkinson’s disease (PD). The lipid shells of the perfluorocarbon gas MDCs were covalently conjugated to antibodies with binding specificity to AAVs. Following systemic (iv) delivery of AAV.SIRT3-myc MDCs, MR-g-FUS was used to deliver SIRT3-myc to brain regions affected in PD. SIRT3-myc expression was determined post mortem, using immunohistochemistry.ResultsAn in vitro, SH-SY5Y cell culture model was used to show that the localized destruction of MDCs using ultrasound exposures within biological safety limits dissociated AAV2-GFP (green fluorescent protein) from the MDCs in the targeted area while maintaining their transduction capacity. In rats, MR-g-FUS resulted in BBB permeabilization in the striatum and substantia nigra (SNc). SIRT3-myc was expressed in the striatum, but not the SNc.ConclusionThese studies demonstrate that MDCs combined with MR-g-FUS are an effective method for delivery of viral vector gene therapies, such as AAV.SIRT3, to brain regions affected in PD. This technology may prove useful as a disease-modifying strategy in PD and other neurodegenerative disorders.     

DFT-based study of the structural,optoelectronic, mechanical and magnetic properties of Ti3AC2 (A = P,As, Cd) for coating applications

The first-principles approach has been used while employing the Perdew–Burke–Ernzerhof exchange-correlation functional of generalized gradient approximation (PBE-GGA) along with the Hubbard parameter to study the structural, optoelectronic, mechanical and magnetic properties of titanium-based MAX materials Ti₃AC₂ (A = P, As, Cd) for the first time. As there is no band gap found between the valence and conduction bands in the considered materials, these compounds belong to the conductor family of materials. A mechanical analysis carried out at pressures of 0 GPa to 20 GPa and the calculated elastic constants C_ij reveal the stability of these materials. Elastic parameters, i.e., Young''s, shear and bulk moduli, anisotropy factor and Poisson''s ratio, have been investigated in the framework of the Voigt–Reuss–Hill approximation. The calculated values of relative stiffness are found to be greater than ½ for Ti₃PC₂ and Ti₃AsC₂, which indicates that these compounds are closer to typical ceramics, which possess low damage tolerance and fracture toughness. Optical parameters, i.e., dielectric complex function, refractive index, extinction coefficient, absorption coefficient, loss function, conductivity and reflectivity, have also been investigated. These dynamically stable antiferromagnetic materials might have potential applications in advanced electronic and magnetic devices. Their high strength and significant hardness make these materials potential candidates as hard coatings.

The first-principles approach has used the Perdew–Burke–Ernzerhof exchange-correlation functional of generalized gradient approximation along with the Hubbard parameter to study various properties of titanium-based MAX materials Ti₃AC₂ (A = P, As, Cd).     

Clinical and scanning electron microscopic features of invasive cervical resorption in a maxillary molar

This case report presents clinical and morphological features of severe invasive cervical resorption (ICR) involving a maxillary first molar. Surface morphology of the ICR defect that extended into enamel was studied using a scanning electron microscope. The topography and morphology of resorbed enamel and pulpal surfaces are described. The pulpal space was characterized by proliferation of fibrovascular tissue invaded by a number of > or = 15-microm-large dentinoclastlike cells. The vertical orientation and hexagonal geometric outlines of enamel rods indicated that the resorptive defect had extended into the outer surface of enamel. Preferential odontoclastic dissolution of interprismatic enamel was noted. Deposits of a cementumlike substance were noticed on enamel surfaces, indicating that resorptive process was coupled with repair. Complete destruction of dentin was associated with no response by the tooth to cold stimulus, supporting the hydrodynamic theory of dentinal sensitivity. The results of this study indicate that in addition to predentin and cementum, the outer surface enamel may be resistant to the resorptive process as well.     

Dermatofibrosarcoma Protuberans at the Site of a Central Venous Line

Dermatofibrosarcoma protuberans (DFSP) is a locally aggressive cutaneous tumor that usually does not metastasize. Clinically, it may present as a reddish macule to protuberant nodule affecting the trunk and proximal extremities of young and middle-aged adults. Histologically, it is characterized by a monomorphous storiform proliferation of spindle cells, involving the dermis and hypodermis, with a honeycomb pattern of infiltration of the subcutaneous fat. In case of difficulty in diagnosis, immunohistochemical markers (especially CD34) are highly sensitive for DFSP. It is important to remember that the rarity of DFSP, its resemblance to hypertrophied scars and keloids, and its appearance at trauma sites sometimes make the diagnosis of DFSP difficult and delayed. In the literature, DSFP was not described in a child until 1957. Here we report an instance of DFSP at an unusual site in a 9-year-old child, which was the location of a previous central venous line insertion in the left supraclavicular area. A complete excision of the tumor with a wide surgical margin of 3cm of visibly uninvolved tissue was performed, followed by a deltopectoral flap and skin split graft. Postoperatively, the patient's general condition was stable and he was discharged after 5 days to be followed up 3 months later in our clinic.