Structural basis for nucleolin recognition of promoter G-quadruplex.

The oncogene promoter G-quadruplex (MycG4) regulates transcription and is a prevalent G4 locus in immortal cells. Nucleolin, a major MycG4-binding protein, exhibits greater affinity for MycG4 than for nucleolin recognition element (NRE) RNA. Nucleolin's four RNA binding domains (RBDs) are essential for high-affinity MycG4 binding.

Chang Gung Forum: An Exemplary Strategy for Implementing a Multidisciplinary Network of Experts in Craniofacial Anomalies.

Introduction: The Chang Gung Forum has been dedicated to the care of craniofacial anomalies since 2000. This annual continuing medical education program focuses on orofacial cleft and surgery-first orthognathic surgery by providing up-to-date information and management guidelines. This study explored how the Chang Gung Forum has influenced medical perspectives, decisions, and practices in a multidisciplinary craniofacial team.

Parathyroid Hormone Therapy for Managing Chronic Hypoparathyroidism: A Systematic Review and Meta-Analysis.

The efficacy and safety of parathyroid hormone (PTH) therapy for managing long-term hypoparathyroidism is being evaluated in ongoing clinical trials. We undertook a systematic review and meta-analysis of currently available randomized controlled trials to investigate the benefits and harms of PTH therapy and conventional therapy in the management of patients with chronic hypoparathyroidism. To identify eligible studies, published in English, we searched Embase, PubMed, and Cochrane CENTRAL from inception to May 2022.

Complications, Symptoms, Presurgical Predictors in Patients With Chronic Hypoparathyroidism: A Systematic Review.

The complications and symptoms of hypoparathyroidism remain incompletely defined. Measuring serum parathyroid hormone (PTH) and calcium levels early after total thyroidectomy may predict the development of chronic hypoparathyroidism. The study aimed (i) to identify symptoms and complications associated with chronic hypoparathyroidism and determine the prevalence of those symptoms and complications (Part I), and (ii) to examine the utility of early postoperative measurements of PTH and calcium in predicting chronic hypoparathyroidism (Part II).

Cancer risk with topical calcineurin inhibitors, pimecrolimus and tacrolimus, for atopic dermatitis: a systematic review and meta-analysis.

Background: Atopic dermatitis is a prevalent condition in children and can be effectively managed with medications such as topical calcineurin inhibitors (pimecrolimus or tacrolimus). A key unresolved safety concern is whether use of topical calcineurin inhibitors is associated with cancer. We systematically reviewed the risk of cancer in patients with atopic dermatitis exposed to topical calcineurin inhibitors.

Impact of the Different Types of Le Fort I Maxillary Surgical Movement on Nasal Width Changes: A Photogrammetric Analysis.

Background: Le Fort I maxillary movements affect nasal width, but nasal width changes with specific movement types have not been formally addressed to date.

Objectives: The purpose of this study was to analyze and compare the changes in nasal width with different maxillary movements.

Methods: A retrospective study was performed among consecutive patients who underwent bimaxillary orthognathic surgery (n = 138) and who were grouped based on the type of maxillary movement (ie, maxillary advancement with intrusion [MAI], maxillary advancement with extrusion [MAE], and maxillary setback with intrusion [MSI]).

History and Evolution of Orthognathic Surgery at Chang Gung Craniofacial Center: Lessons Learned From 35-Year Experience.

Background: Modern orthognathic surgery (OGS) was established on the basis of contributions from multidisciplinary centers worldwide. This study reports the history and evolution of OGS at the Chang Gung Craniofacial Center (CGCC) and identifies the lessons learned from 35 years of experience.

Methods: The total number of OGS procedures managed by the CGCC multidisciplinary team between 1981 and 2016 was determined.

Structures of 1:1 and 2:1 complexes of BMVC and MYC promoter G-quadruplex reveal a mechanism of ligand conformation adjustment for G4-recognition.

BMVC is the first fluorescent probe designed to detect G-quadruplexes (G4s) in vivo. The MYC oncogene promoter forms a G4 (MycG4) which acts as a transcription silencer. Here, we report the high-affinity and specific binding of BMVC to MycG4 with unusual slow-exchange rates on the NMR timescale.

Electrophoretic Mobility Shift Assay and Dimethyl Sulfate Footprinting for Characterization of G-Quadruplexes and G-Quadruplex-Protein Complexes.

DNA G-quadruplexes are globular nucleic acid secondary structures which occur throughout the human genome under physiological conditions. There is accumulating evidence supporting G-quadruplex involvement in a number of important aspects of genome functions, including transcription, replication, and genomic stability, and that protein and enzyme recognition of G-quadruplexes may represent a key event to regulate physiological or pathological pathways. Two important techniques to study G-quadruplexes and their protein interactions are the electrophoretic mobility shift assay (EMSA) and dimethyl sulfate (DMS) footprinting assay.

NMR Studies of G-Quadruplex Structures and G-Quadruplex-Interactive Compounds.

G-quadruplexes are noncanonical, four-stranded nucleic acid secondary structures formed in sequences containing consecutive runs of guanines. These G-quadruplex structures have been found to form in nucleic acid regions of biological significance, including human telomeres, gene promoters, and untranslated regions of mRNA. Thus, they are considered attractive therapeutic targets.

Ligand Selectivity in the Recognition of Protoberberine Alkaloids by Hybrid-2 Human Telomeric G-Quadruplex: Binding Free Energy Calculation, Fluorescence Binding, and NMR Experiments.

The human telomeric G-quadruplex (G4) is an attractive target for developing anticancer drugs. Natural products protoberberine alkaloids are known to bind human telomeric G4 and inhibit telomerase. Among several structurally similar protoberberine alkaloids, epiberberine (EPI) shows the greatest specificity in recognizing the human telomeric G4 over duplex DNA and other G4s.

Prevalence of hepatitis C virus infection and the IL28B genotype polymorphism among blood donors and high-risk populations.

Introduction: To study the prevalence of hepatitis C virus (HCV) infection in blood donor (BD), haemodialysis (HD) and intravenous drug user (IVDU) populations in Singapore and assess the IL28B polymorphism if HCV positive.

Methods: The BD population were healthy volunteers, the HD population were patients who were on haemodialysis for at least six months of follow-up between January 2009 and December 2014. IVDU population was from inmates at halfway houses who consented.

Molecular Recognition of the Hybrid-2 Human Telomeric G-Quadruplex by Epiberberine: Insights into Conversion of Telomeric G-Quadruplex Structures.

Human telomeres can form DNA G-quadruplex (G4), an attractive target for anticancer drugs. Human telomeric G4s bear inherent structure polymorphism, challenging for understanding specific recognition by ligands or proteins. Protoberberines are medicinal natural-products known to stabilize telomeric G4s and inhibit telomerase.

Resolving the Ligand-Binding Specificity in c-MYC G-Quadruplex DNA: Absolute Binding Free Energy Calculations and SPR Experiment.

We report the absolute binding free energy calculation and surface plasmon resonance (SPR) experiment for ligand binding with the c-MYC G-quadruplex DNA. The unimolecular parallel DNA G-quadruplex formed in nuclease hypersensitivity element III of the c-MYC gene promoter regulates the c-MYC transcription and is recognized as an emerging drug target for cancer therapy. Quindoline derivatives have been shown to stabilize the G-quadruplex and inhibit the c-MYC expression in cancer cells.

Human Telomeric G-Quadruplex Structures and G-Quadruplex-Interactive Compounds.

G-quadruplexes are noncanonical secondary structures formed in DNA sequences containing consecutive runs of guanines. It has been shown that the 3' G-rich single-stranded overhangs of human telomeres can form G-quadruplex structures, and the human telomeric DNA G-quadruplexes are considered attractive targets for anticancer drugs. G-quadruplex-interactive compounds have been shown to inhibit telomerase access as well as telomere capping.

Structurally Diverse Alkaloids from the Seeds of Peganum harmala.

Investigation of the alkaloids from Peganum harmala seeds yielded two pairs of unique racemic pyrroloindole alkaloids, (±)-peganines A-B (1-2); two rare thiazole derivatives, peganumals A-B (3-4); six new β-carboline alkaloids, pegaharmines F-K (5-10); and 12 known analogues. Their structures, including stereochemistry, were elucidated through spectroscopic analyses, quantum chemistry calculations, and single-crystal X-ray diffraction. Notably, the incorporation of pyrrole and indole moieties in peganines A-B, thiazole fragments in peganumals A-B, and a C-1 α,β-unsaturated ester motif in pegaharmine F (5) are all rare, and their presence in the genus Peganum were demonstrated for the first time.

A Series of β-Carboline Alkaloids from the Seeds of Peganum harmala Show G-Quadruplex Interactions.

In this study, we screened 17 medicinal plants for binding activity to G-quadruplex d(TTGGGTT)4 by (1)H NMR spectroscopy and found that the crude extract of Peganum harmala L. seeds showed the most potential binding activity. Subsequently, (1)H NMR- and bioassay-guided isolation of the extract of P.

DNA Recognition by a Novel Bis-Intercalator, Potent Anticancer Drug XR5944.

XR5944 is a potent anticancer drug with a novel DNA binding mode: DNA bisintercalationg with major groove binding. XR5944 can bind the estrogen response element (ERE) sequence to block ER-ERE binding and inhibit ERα activities, which may be useful for overcoming drug resistance to currently available antiestrogen treatments. This review discusses the progress relating to the structure and function studies of specific DNA recognition of XR5944.

DNA G-quadruplex and its potential as anticancer drug target.

G-quadruplex secondary structures are four-stranded globular nucleic acid structures form in the specific DNA and RNA G-rich sequences with biological significance such as human telomeres, oncogene-promoter regions, replication initiation sites, and 5' and 3'-untranslated (UTR) regions. The non-canonical G-quadruplex secondary structures can readily form under physiologically relevant ionic conditions and are considered to be new molecular target for cancer therapeutics. This review discusses the essential progress in our lab related to the structures and functions of biologically relevant DNA G-quadruplexes in human gene promoters and telomeres, and the opportunities presented for the development of G-quadruplex-targeted small- molecule drugs.

Selective lighting up of epiberberine alkaloid fluorescence by fluorophore-switching aptamer and stoichiometric targeting of human telomeric DNA G-quadruplex multimer.

Aptamers, that exist naturally in living cells as functional elements and can switch nonfluorescent natural targets to fluorophores, are very useful in developing highly sensitive and selective biosensors and screening functional agents. This work demonstrates that human telomeric G-quadruplex (HTG) can serve as a potential fluorophore-switching aptamer (FSA) to target a natural isoquinoline alkaloid. We found that, among the G-quadruplexes studied here and the various structurally similar alkaloids including epiberberine (EPI), berberine (BER), palmatine (PAL), jatrorrhizine (JAT), coptisine (COP), worenine (WOR), sanguinarine (SAN), chelerythrine (CHE), and nitidine (NIT), only the HTG DNA, especially with a 5'-TA-3' residue at the 5' end of the G-quadruplex tetrad (5'-TAG3(TTAG3)3-3', TA[Q]) as the minimal sequence, is the most efficient FSA to selectively light up the EPI fluorescence.

Solution structure of a 2:1 complex of anticancer drug XR5944 with TFF1 estrogen response element: insights into DNA recognition by a bis-intercalator.

XR5944, a deoxyribonucleic acid (DNA) bis-intercalator with potent anticancer activity, can bind the estrogen response element (ERE) sequence to inhibit estrogen receptor-α activities. This novel mechanism of action may be useful for overcoming drug resistance to currently available antiestrogen treatments, all of which target the hormone-receptor complex. Here we report the nuclear magnetic resonance solution structure of the 2:1 complex of XR5944 with the naturally occurring TFF1-ERE, which exhibits important and unexpected features.

The major G-quadruplex formed in the human BCL-2 proximal promoter adopts a parallel structure with a 13-nt loop in K+ solution.

The human BCL-2 gene contains a 39-bp GC-rich region upstream of the P1 promoter that has been shown to be critically involved in the regulation of BCL-2 gene expression. Inhibition of BCL-2 expression can decrease cellular proliferation and enhance the efficacy of chemotherapy. Here we report the major G-quadruplex formed in the Pu39 G-rich strand in this BCL-2 promoter region.