Integrating computational methods guided the discovery of phytochemicals as potential Pin1 inhibitors for cancer: pharmacophore modeling, molecular docking, MM-GBSA calculations and molecular dynamics studies.

Pin1 is a pivotal player in interactions with a diverse array of phosphorylated proteins closely linked to critical processes such as carcinogenesis and tumor suppression. Its axial role in cancer initiation and progression, coupled with its overexpression and activation in various cancers render it a potential candidate for the development of targeted therapeutics. While several known Pin1 inhibitors possess favorable enzymatic profiles, their cellular efficacy often falls short.

Peristaltic motion of Jeffrey fluid with nonlinear mixed convection.

Since previous few decays the consideration of non-Newtonian liquids motion due to its immense usages in medicine, biology, industrial procedures, chemistry of catalysts and in environment. Various studies examine the significance of bio-materials flow in physiological procedures to explore the cure of diagnosed symptoms of disease appearing during movement in a human physiological system. To illustrate the characteristics of physiological liquids various non-Newtonian models have been proposed, but yet no such single liquid model is exploited which describes all the properties of nonlinear behaving liquids.

Design of new Mcl-1 inhibitors for cancer using fragments hybridization, molecular docking, and molecular dynamics studies.

Apoptosis is a critical process that regulates cell survival and death and plays an essential role in cancer development. The Bcl-2 protein family, including myeloid leukemia 1 (Mcl-1), is a key regulator of the intrinsic apoptosis pathway, and its overexpression in many human cancers has prompted efforts to develop Mcl-1 inhibitors as potential anticancer agents. In this study, we aimed to design new Mcl-1 inhibitors using various computational techniques.

Marine-Derived Compounds for CDK5 Inhibition in Cancer: Integrating Multi-Stage Virtual Screening, MM/GBSA Analysis and Molecular Dynamics Investigations.

Cyclin-dependent kinase 5 (CDK5) plays a crucial role in various biological processes, including immune response, insulin secretion regulation, apoptosis, DNA (deoxyribonucleic acid) damage response, epithelial-mesenchymal transition (EMT), cell migration and invasion, angiogenesis, and myogenesis. Overactivation of CDK5 is associated with the initiation and progression of cancer. Inhibiting CDK5 has shown potential in suppressing cancer development.

Discovery of dual-target natural antimalarial agents against DHODH and PMT of : pharmacophore modelling, molecular docking, quantum mechanics, and molecular dynamics simulations.

Malaria is a lethal disease that claims thousands of lives worldwide annually. The objective of this study was to identify new natural compounds that can target two enzymes; m Dihydroorotate dehydrogenase (DHODH) and phosphoethanolamine methyltransferase (PMT). To accomplish this, e-pharmacophore modelling and molecular docking were employed against DHODH.

Modulation of NRF2/KEAP1-Mediated Oxidative Stress for Cancer Treatment by Natural Products Using Pharmacophore-Based Screening, Molecular Docking, and Molecular Dynamics Studies.

Oxidative stress plays a significant role in the development of cancer. Inhibiting the protein-protein interaction (PPI) between Keap1 and Nrf2 offers a promising strategy to activate the Nrf2 antioxidant pathway, which is normally suppressed by the binding of Keap1 to Nrf2. This study aimed to identify natural compounds capable of targeting the kelch domain of KEAP1 using structure-based drug design methods.

Postoperative Fillers Reduce Revision Rates in Rhinoplasty.

Background: Rhinoplasty is a complex procedure with revision rates of up to 17%. Even minor imperfections after surgery can be significant.

Objectives: This review aims to investigate the use of hyaluronic acid (HA) fillers postaesthetic rhinoplasty and assess the rhinoplasty practice of the senior author.

Insight into the assembly of lipid-hyaluronan complexes in osteoarthritic conditions.

Interactions between molecules in the synovial fluid and the cartilage surface may play a vital role in the formation of adsorbed films that contribute to the low friction of cartilage boundary lubrication. Osteoarthritis (OA) is the most common degenerative joint disease. Previous studies have shown that in OA-diseased joints, hyaluronan (HA) not only breaks down resulting in a much lower molecular weight (MW), but also its concentration is reduced ten times.

Closed Rhinoplasty: A Single Surgeon Experience of 238 Cases over 2 Years.

Closed rhinoplasty is currently losing favour as a method of rhinoplasty reshaping procedure. Open rhinoplasties are usually performed by surgeons because of the greater degree of visualisation of the cartilages and bones within the nose that need to be reshaped. Because of the criticisms of closed rhinoplasty the senior author performed an audit of his outcomes to determine whether closed rhinoplasty still has a role to play in the armamentarium of the plastic surgeon.

SANS characterization of time dependent, slow molecular exchange in an SDS micellar system.

We have investigated the molecular exchange of sodium dodecyl sulfate (SDS) micelles in aqueous solution by time-resolved small angle neutron scattering (TR-SANS) measurements as a function of the surfactant and salt concentration. Starting with deuterated (d-SDS) and protonated (h-SDS) SDS micelles, surfactant exchange across the micelles leads to a randomized distribution of d-SDS and h-SDS within each micelle. By employing the contrast matching technique, we have studied this randomization process which is a direct measure of the molecular exchange of this system.

Pathological cardiolipin-promoted membrane hemifusion stiffens pulmonary surfactant membranes.

Lower tract respiratory diseases such as pneumonia are pervasive, affecting millions of people every year. The stability of the air/water interface in alveoli and the mechanical performance during the breathing cycle are regulated by the structural and elastic properties of pulmonary surfactant membranes (PSMs). Respiratory dysfunctions and pathologies often result in, or are caused by, impairment of the PSMs.

Correction: Nanoscale insight into the degradation mechanisms of the cartilage articulating surface preceding OA.

Correction for 'Nanoscale insight into the degradation mechanisms of the cartilage articulating surface preceding OA' by Tooba Shoaib, et al., Biomater. Sci.

Nanoscale insight into the degradation mechanisms of the cartilage articulating surface preceding OA.

Osteoarthritis (OA) is a degenerative joint disease and a leading cause of disability globally. In OA, the articulating surface of cartilage is compromised by fissures and cracks, and sometimes even worn away completely. Due to its avascular nature, articular cartilage has a poor self-healing ability, and therefore, understanding the mechanisms underlying degradation is key for OA prevention and for optimal design of replacements.

Influence of Loading Conditions and Temperature on Static Friction and Contact Aging of Hydrogels with Modulated Microstructures.

Biological tribosystems enable diverse functions of the human body by maintaining extremely low coefficients of friction via hydrogel-like surface layers and a water-based lubricant. Although stiction has been proposed as a precursor to damage, there is still a lack of knowledge about its origin and its relation to the hydrogel's microstructure, which impairs the design of soft matter as replacement biomaterials. In this work, the static friction of poly(acrylamide) hydrogels with modulated composition was investigated by colloidal probe lateral force microscopy as a function of load, temperature, and loading time.

Stick-Slip Friction Reveals Hydrogel Lubrication Mechanisms.

The lubrication behavior of the hydrated biopolymers that constitute tissues in organisms differs from that outlined by the classical Stribeck curve, and studying hydrogel lubrication is a key pathway to understand the complexity of biolubrication. Here, we have investigated the frictional characteristics of polyacrylamide (PAAm) hydrogels with various acrylamide concentrations, exhibiting Young's moduli (E) that range from 1 to 40 kPa, as a function of applied normal load and sliding velocities by colloid probe lateral force microscopy. The speed-dependence of the friction force shows an initial decrease in friction with increasing velocity, while, above a transition velocity V*, friction increases with speed.

Self-adaptive hydrogels to mineralization.

Mineralized biological tissues, whose behavior can range from rigid to compliant, are an essential component of vertebrates and invertebrates. Little is known about how the behavior of mineralized yet compliant tissues can be tuned by the degree of mineralization. In this work, a synthesis route to tune the structure and mechanical response of agarose gels via ionic crosslinking and mineralization has been developed.

Assembly, Morphology, Diffusivity, and Indentation of Hydrogel-Supported Lipid Bilayers.

Recognizing the limitations of solid-supported lipid bilayers to reproduce the behavior of cell membranes, including bendability, transmembrane protein inclusion, and virus entry, this study describes a novel biomimetic system for cell membranes with the potential to overcome these and other limitations. The developed strategy utilizes a hydrogel with tunable mechanical behavior that resembles those of living cells as the soft support for the phospholipid bilayer, while a polyelectrolyte multilayer film serves as an intermediate layer to facilitate the self-assembly of the lipid bilayer on the soft cushion. Quartz crystal microbalance studies show that, upon coming into contact with the polyelectrolyte film, vesicles fuse and rupture to yield a robust lipid bilayer.

Pleomorphic adenomas: post-operative radiotherapy is unnecessary following primary incomplete excision: a retrospective review.

Background: Current standard treatment of Pleomorphic Salivary Adenoma (PSA) of the Parotid Gland is by surgical excision. The management of incomplete excision remains undecided with post-operative radiotherapy advocated by some and observation by others.

Methods: 190 patients who underwent resection of PSA of the parotid gland within the West of Scotland region from 1981 to 2008 were identified and data collected.

Decision-making and involvement of women with previous C-section in choosing their mode of delivery.

Objective: To determine the attitude and factors leading to decision regarding the mode of delivery in women with previous experience of C-section.

Methods: The cross-sectional study was conducted at Maternity Unit of Jinnah Postgraduate Medical Centre, Karachi, from January to August 2008, and involved 150 women with one previous C-section without any recurrent cause. All women had a parity of two or more.

The functional intraoral Glasgow scale in floor of mouth carcinoma: longitudinal assessment of 62 consecutive patients.

The functional integrity of the floor of the mouth (FOM) is essential in maintaining tongue mobility, deglutition, and control and disposal of saliva. The present study focused on reporting oral function using functional intraoral Glasgow scale (FIGS) in patients who had surgical ablation and reconstruction of FOM carcinoma with or without chemo-radiotherapy. The study included patients who had surgical treatment of floor of mouth cancer in two regional head and neck units in Glasgow, UK between January 2006 and August 2007.

Implications of a positive sentinel node in oral squamous cell carcinoma.

Background: The role of sentinel node biopsy in head and neck cancer is currently being explored. Patients with positive sentinel nodes were investigated to establish if additional metastases were present in the neck, their distribution, and their impact on outcome.

Methods: In all, 109 patients (n = 109) from 15 European centers, with cT1/2,N0 tumors, and a positive sentinel lymph node were identified.

Guideline for prophylactic feeding tube insertion in patients undergoing resection of head and neck cancers.

Background: Supplementary nutrition is an important aspect of the multidisciplinary management of head and neck cancer patients. In our unit, method of feeding is based on an arbitrary predicted duration of overall treatment (<30 days indicates NG feeding, >30 days prophylactic PEG tube insertion is appropriate). This paper provides a guideline to assist in choosing the feeding method early on to avoid the need for later PEG insertion in those who were initially fed orally or via NG tube.