A NRAS mRNA G-quadruplex structure-targeting small-molecule ligand reactivating DNA damage response in human cancer cells for combination therapy with clinical PI3K inhibitors.

The Neuroblastoma RAS (NRAS) oncogene homologue plays crucial roles in diverse cellular processes such as cell proliferation, survival, and differentiation. Several strategies have been developed to inhibit NRAS or its downstream effectors; however, there is no effective drug available to treat NRAS-driven cancers and thus new approaches are needed to be established. The mRNA sequence expressing NRAS containing several guanine(G)-rich regions may form quadruplex structures (G4s) and regulate NRAS translation.

Mitochondria-Selective Dicationic Small-Molecule Ligand Targeting G-Quadruplex Structures for Human Colorectal Cancer Therapy.

Mitochondria are important drug targets for anticancer and other disease therapies. Certain human mitochondrial DNA sequences capable of forming G-quadruplex structures (G4s) are emerging drug targets of small molecules. Despite some mitochondria-selective ligands being reported for drug delivery against cancers, the ligand design is mostly limited to the triphenylphosphonium scaffold.

Discovery of a novel class of rosmarinic acid derivatives as antibacterial agents: Synthesis, structure-activity relationship and mechanism of action.

Twenty-seven rosmarinic acid derivatives were synthesized, among which compound RA-N8 exhibited the most potent antibacterial ability. The minimum inhibition concentration of RA-N8 against both S. aureus (ATCC 29213) and MRSA (ATCC BAA41 and ATCC 43300) was found to be 6 μg/mL, and RA-N8 killed E.

Structurally diverse G-quadruplexes as the noncanonical nucleic acid drug target for live cell imaging and antibacterial study.

The formation of G-quadruplex structures (G4s) from guanine (G)-rich nucleic acid sequences of DNA and RNA stabilized with monovalent cations, typically K and Na, under physiological conditions, has been verified experimentally and some of them have high-resolution NMR or -ray crystal structures; however, the biofunction of these special noncanonical secondary structures of nucleic acids has not been fully understood and their existence is still controversial at present. It is generally believed that the folding and unfolding of G4s is a transient process. Accumulating evidence has shown that G4s may play a role in the regulation of certain important cellular functions including telomere maintenance, replication, transcription and translation.

Rational structural modification of the isatin scaffold to develop new and potent antimicrobial agents targeting bacterial peptidoglycan glycosyltransferase.

A series of isatin derivatives bearing three different substituent groups at the N-1, C-3 and C-5 positions of the isatin scaffold were systematically designed and synthesized to study the structure-activity relationship of their inhibition of bacterial peptidoglycan glycosyltransferase (PGT) activity and antimicrobial susceptibility against , and methicillin-resistant (MRSA (BAA41)) strains. The substituents at these sites are pointing towards three different directions from the isatin scaffold to interact with the amino acid residues in the binding pocket of PGT. Comparative studies of their structure-activity relationship allow us to gain better understanding of the direction of the substituents that contribute critical interactions leading to inhibition activity against the bacterial enzyme.

N-Terminal selective modification of peptides and proteins using 2-ethynylbenzaldehydes.

Selective modification of the N-terminus of peptides and proteins is a promising strategy for single site modification methods. Here we report N-terminal selective modification of peptides and proteins by using 2-ethynylbenzaldehydes (2-EBA) for the production of well-defined bioconjugates. After reaction screening with a series of 2-EBA, excellent N-terminal selectivity is achieved by the reaction in slightly acidic phosphate-buffered saline using 2-EBA with electron-donating substituents.

Weightbearing Digital Tomosynthesis of Foot and Ankle Arthritis: Comparison With Radiography and Simulated Weightbearing CT in a Prospective Study.

Objective: Foot and ankle arthritis is common and debilitating. Weightbearing radiography is the reference standard for evaluating alignment, but overlapping bones and hardware limit evaluation for osteoarthritic bony detail. The purpose of this study was to evaluate whether digital tomosynthesis (DTS) can yield reliable quantitative alignment values, as radiography does with its weightbearing capability, and good qualitative osteoarthritic detail, as CT does.

Cuff tear arthropathy shoulder hemiarthroplasty: a radiographic outcome study.

Objective: Cuff tear arthropathy (CTA) head prosthesis has recently become an alternative to standard shoulder hemiarthroplasty in patients with severe cuff disease by offering an increased surface area and decreased impingement. The purpose of this study is to evaluate the radiographic outcomes of CTA prosthesis and to correlate them with clinical outcomes.

Materials And Methods: In this retrospective study of CTA hemiarthroplasties over an 11-year period, two radiologists reviewed pre-/postoperative radiographs and clinical data.

A Case of Discontinued Proximal Limb of a Ventriculoperitoneal Shunt With Patent Fibrous Tract.

Radionuclide shuntogram is important in the evaluation of cerebrospinal fluid (CSF) shunts complications such as mechanical failure, malpositioning, pseudocyst, or overdrainage. We present here a case of congenital hydrocephalus and posterior fossa cyst with multiple shunt procedures and revisions with breakage of the proximal tube of the ventriculoperitoneal shunt but preserved CSF drainage through the patent fibrous tract. Careful correlation with SPECT/CT images helped confirm the breakage and exclude CSF leak outside of the tract, which was suspected on planar images.

Optimal timing of first posttreatment FDG PET/CT in head and neck squamous cell carcinoma.

Background: The optimal timing for the initial posttreatment fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT scan after definitive treatment of head and neck squamous cell carcinoma (HNSCC) is unclear.

Methods: We conducted a retrospective review of 247 patients with definitively treated nonmetastatic HNSCC. First posttreatment PET/CT scans were grouped into: <7 weeks, 7 to 10 weeks, 11 to 14 weeks, and ≥15 weeks.

VEGF microsphere technology to enhance vascularization in fat grafting.

Vascularization is crucial for implantation of engineered tissues in reconstructive surgery. Polypeptides encapsulated in microspheres can be efficiently transported to their site of action and released in a sustained dosage. We evaluated the effect of delivering vascular endothelial growth factor (VEGF)-encapsulated microspheres in a lipoaspirate scaffold on vascularization and tissue survival.