Clinical characteristics, densitometric parameters and outcomes of patients with atypical femoral fractures related to bisphosphonate treatment for osteoporosis.

Purpose: We described the clinical and densitometric characteristics and treatment outcomes of patients who developed atypical femoral fractures (AFF) while on bisphosphonate for osteoporosis.

Methods: We performed a retrospective cohort study including all adults aged ≥50 years who developed AFF while on bisphosphonates between 1 January 2008 and 31 December 2020, and subsequently managed in the Osteoporosis Centre at Queen Mary Hospital in Hong Kong. A control group of patients who developed fragility hip fractures while on bisphosphonates in the same period was included for comparison.

Development of Fluorescent Turn-On Probes for CAG-RNA Repeats.

Fluorescent sensing of nucleic acids is a highly sensitive and efficient bioanalytical method for their study in cellular processes, detection and diagnosis in related diseases. However, the design of small molecule fluorescent probes for the selective binding and detection of RNA of a specific sequence is very challenging because of their diverse, dynamic, and flexible structures. By modifying a bis(amidinium)-based small molecular binder that is known to selectively target RNA with CAG repeats using an environment-sensitive fluorophore, a turn-on fluorescent probe featuring aggregation-induced emission (AIE) is successfully developed in this proof-of-concept study.

Effect of Inactivated and mRNA COVID-19 Vaccination on Thyroid Function Among Patients Treated for Hyperthyroidism.

Context: Reports of thyroid dysfunction following COVID-19 vaccination included cases of relapse of Graves' disease and worsening of pre-existing Graves' disease. Little is known about the thyroid-specific outcomes among patients treated for hyperthyroidism who have received COVID-19 vaccination.

Objective: Among patients treated for hyperthyroidism, we evaluated factors associated with not receiving the COVID-19 vaccination and whether COVID-19 vaccination was associated with thyroid function instability.

Development of Antiviral CVC (Chief Value Cotton) Fabric.

The outbreak of COVID-19 has already generated a huge societal, economic and political losses worldwide. The present study aims to investigate the antiviral activity of Poly(hexamethylene biguanide) hydrochloride (PHMB) treated fabric against COVID-19 by using the surrogate Feline coronavirus. The antiviral analysis indicated that up to 94% of coronavirus was killed after contacting the CVC fabric treated with PHMB for 2 h, which suggests that PHMB treated fabric could be used for developing protective clothing and beddings with antiviral activity against coronavirus and can play a role in fighting the transmission of COVID-19 in the high-risk places.

Study on the Development of Antiviral Spandex Fabric Coated with Poly(hexamethylene biguanide) Hydrochloride (PHMB).

The spread of COVID-19 has brought about huge losses around the world. This study aims to investigate the applicability of PHMB used for developing antiviral spandex clothing against coronavirus. PHMB was qualitatively determined on the surface of spandex fabrics by using BPB.

CAG RNAs induce DNA damage and apoptosis by silencing expression in polyglutamine degeneration.

DNA damage plays a central role in the cellular pathogenesis of polyglutamine (polyQ) diseases, including Huntington's disease (HD). In this study, we showed that the expression of untranslatable expanded CAG RNA per se induced the cellular DNA damage response pathway. By means of RNA sequencing (RNA-seq), we found that expression of the () gene was down-regulated in mutant CAG RNA-expressing cells.

Outcomes of abstracts presented at IADR general meetings in 2014 and 2015.

Introduction Abstract presentations at scientific meetings provide a platform to share and discuss new research. It would be desirable if the abstracts were subsequently published in peer-reviewed journals as this is the most accepted method to allow the dissemination of scientific research.Aims To determine the publication rate of abstracts presented at the International Association for Dental Research (IADR) general sessions in 2014 and 2015, and factors involved from presentation to publication.

Exclusion of unsuitable CNS drug candidates based on their physicochemical properties and unbound fractions in biomatrices for brain microdialysis investigations.

Microdialysis has been the only direct method of continuously measuring the unbound drug concentrations in extracellular fluid at a specific brain region with respect to time in the same animal. However, not every compound is suitable for microdialysis system as demonstrated by their inconsistent "by gain" and "by loss" in-vitro microdialysis probe recoveries leading to over- or under- estimated in-vivo concentrations. Therefore, our current study was proposed aiming to develop simple exclusion criteria for drug candidates that are not suitable for microdialysis system investigation.

AQAMAN, a bisamidine-based inhibitor of toxic protein inclusions in neurons, ameliorates cytotoxicity in polyglutamine disease models.

Polyglutamine (polyQ) diseases are a group of dominantly inherited neurodegenerative disorders caused by the expansion of an unstable repeat in the coding region of the affected genes. Hallmarks of polyQ diseases include the accumulation of misfolded protein aggregates, leading to neuronal degeneration and cell death. PolyQ diseases are currently incurable, highlighting the urgent need for approaches that inhibit the formation of disaggregate cytotoxic polyQ protein inclusions.

Efficient brain uptake and distribution of an expanded CAG RNA inhibitor DB213 via intranasal administration.

DB213 is an expanded CAG RNA inhibitor targeting polyglutamine diseases. This current study aims to investigate biopharmaceutic characteristics of DB213 as well as its brain uptake and distribution in C57 wild type mice, R6/2 Huntington's disease mice and Sprague-Dawley (SD) rats via intranasal administration. The biopharmaceutic characteristics of DB213 were investigated in vitro using Calu-3/MDCK/HEK293 cell lines and brain slices for its membrane transport, equilibrium dialysis for its plasma protein/brain tissue bindings and liver/brain microsomes incubation for its enzyme kinetics profiles.

Statistical Design of Experiment (DoE) based development and optimization of DB213 in situ thermosensitive gel for intranasal delivery.

DB213 is an HIV-1 replication inhibitor targeting the Central Nervous System for the treatment of HIV-associated neurocognitive disorders. Current study aims to develop an in situ thermosensitive gelling system for intranasal delivery of DB213 facilitated by Statistical Design of Experiment (DoE) to conduct a more efficient experimentation by extracting the maximum amount of information from limited experiments. In our current study, information was extracted from twenty-five experimental designs from MODDE Software and a mathematical model was successfully developed to predict formulations to achieve desired performance as well as to analyze relationships between the amount of Pluronic F-127, Pluronic F-68, Chitosan, DB213 and the performances of in situ thermosensitive gels.

Demonstration of Direct Nose-to-Brain Transport of Unbound HIV-1 Replication Inhibitor DB213 Via Intranasal Administration by Pharmacokinetic Modeling.

Intranasal administration could be an attractive alternative route of administration for the delivery of drugs to the central nervous system (CNS). However, there are always doubts about the direct transport of therapeutics from nasal cavity to the CNS since there are only limited studies on the understanding of direct nose-to-brain transport. Therefore, this study aimed to (1) investigate the existence of nose-to-brain transport of intranasally administered HIV-1 replication inhibitor DB213 and (2) assess the direct nose-to-brain transport of unbound HIV-1 replication inhibitor DB213 quantitatively by a pharmacokinetic approach.

A Potent Inhibitor of Protein Sequestration by Expanded Triplet (CUG) Repeats that Shows Phenotypic Improvements in a Drosophila Model of Myotonic Dystrophy.

Myotonic dystrophy is the most common form of adult-onset muscular dystrophy, originating in a CTG repeat expansion in the DMPK gene. The expanded CUG transcript sequesters MBNL1, a key regulator of alternative splicing, leading to the misregulation of numerous pre-mRNAs. We report an RNA-targeted agent as a possible lead compound for the treatment of myotonic dystrophy type 1 (DM1) that reveals both the promise and challenges for this type of small-molecule approach.

Effective symptomatic treatment for severe and intractable pruritus associated with severe burn-induced hypertrophic scars: A prospective, multicenter, controlled trial.

Background: Burn-induced hypertrophic scars are disfiguring and can be associated with severe and intractable pruritus. No effective treatment modalities are currently available for symptomatic control of pruritus for most patients. We assessed the effect of the Antipruritic Hydrogel (CQ-01) in the symptomatic treatment of severe and intractable pruritus associated with burn-induced hypertrophic scars in a prospective, multicenter, controlled trial.

Pharmacokinetics and brain uptake of HIV-1 replication inhibitor DB213 in Sprague-Dawley rats.

The current study aims to investigate the pharmacokinetics and brain uptake of HIV-1 replication inhibitor DB213 via a developed LC/MS/MS analytical method. A sensitive, selective, accurate and reliable LC/MS/MS method for determination and quantification of DB213 in rat plasma and brain was developed and validated. A triple quadrupole mass spectrometer equipped with electrospray ionization (ESI) source was applied for the detection of DB213 and benzamidine (Internal Standard).

Small molecules that target the toxic RNA in myotonic dystrophy type 2.

Myotonic dystrophy type 2 (DM2) is caused by an expansion of CCTG repeats in the zinc-finger protein gene (ZNF9). Transcribed CCUG repeats sequester muscleblind-like protein 1 (MBNL1), an important alternative splicing regulator, preventing its normal function, leading to the disease phenotype. We describe a series of ligands that disrupt the MBNL1-r(CCUG)n interaction as potential lead agents for developing DM2 therapeutics.

Targeting toxic RNAs that cause myotonic dystrophy type 1 (DM1) with a bisamidinium inhibitor.

A working hypothesis for the pathogenesis of myotonic dystrophy type 1 (DM1) involves the aberrant sequestration of an alternative splicing regulator, MBNL1, by expanded CUG repeats, r(CUG)(exp). It has been suggested that a reversal of the myotonia and potentially other symptoms of the DM1 disease can be achieved by inhibiting the toxic MBNL1-r(CUG)(exp) interaction. Using rational design, we discovered an RNA-groove binding inhibitor (ligand 3) that contains two triaminotriazine units connected by a bisamidinium linker.

A polymeric fastener can easily functionalize liposome surfaces with gadolinium for enhanced magnetic resonance imaging.

Common methods of loading magnetic resonance imaging (MRI) contrast agents into nanoparticles often suffer from challenges related to particle formation, complex chemical modification/purification steps, and reduced contrast efficiency. This study presents a simple, yet advanced process to address these issues by loading gadolinium, an MRI contrast agent, exclusively on a liposome surface using a polymeric fastener. The fastener, so named for its ability to physically link the two functional components together, consisted of chitosan substituted with diethylenetriaminepentaacetic acid (DTPA) to chelate gadolinium, as well as octadecyl chains to stabilize the modified chitosan on the liposome surface.

Orthogonality in organic, polymer, and supramolecular chemistry: from Merrifield to click chemistry.

The concept of orthogonality has been applied to many areas of chemistry, ranging from wave functions to chromatography. But it was Barany and Merrifield's orthogonal protecting group strategy that paved the way for solid phase peptide syntheses, other important classes of biomaterials such as oligosaccharides and oligonucleotides, and ultimately to a term in widespread usage that is focused on chemical reactivity and binding selectivity. The orthogonal protection strategy has been extended to the development of orthogonal activation, and recently the click reaction, for streamlining organic synthesis.

Selective inhibition of MBNL1-CCUG interaction by small molecules toward potential therapeutic agents for myotonic dystrophy type 2 (DM2).

Myotonic dystrophy type 2 (DM2) is an incurable neuromuscular disease caused by expanded CCUG repeats that may exhibit toxicity by sequestering the splicing regulator MBNL1. A series of triaminotriazine- and triaminopyrimidine-based small molecules (ligands 1-3) were designed, synthesized and tested as inhibitors of the MBNL1-CCUG interaction. Despite the structural similarities of the triaminotriazine and triaminopyrimidine units, the triaminopyrimidine-based ligands bind with low micromolar affinity to CCUG repeats (K(d) ∼ 0.

Hydrophobically modified dendrons: developing structure-activity relationships for DNA binding and gene transfection.

This paper develops a structure-activity relationship understanding of the way in which surfactant-like dendrons with hydrophilic spermine surface groups and a variety of lipophilic units at their focal points can self-assemble and subsequently bind to DNA with high affinity. The choice of functional group at the focal point of the dendron and the high tunability of the molecular structure have a very significant impact on DNA binding. Mesoscale modeling of the mode of dendron self-assembly provides a direct insight into how the mode of self-assembly exerts its effect on the DNA binding process.

The effects of microenvironment polarity and dendritic branching of aliphatic hydrocarbon dendrons on the self-assembly of 2-ureido-4-pyrimidinones.

Two series of aliphatic hydrocarbon-based G1-G3 dendritic 2-ureido-4-pyrimidinones (UPy) (S-Gn)₂ and (L-Gn)₂, differing from one another by the distance between the branching juncture to the urea end, were prepared and characterized. These hydrocarbon dendrons were also appended to a p-aminonitrobenzene solvatochromic chromophore in order to probe their microenvironment polarity. While positive solvatochromism was observed which indicated the chromophore was solvent accessible, there was no significant difference between the microenvironment polarities on going from the G1 to the G3 dendrons.