Self-stretching exercises with kinesio taping for management of chronic nonspecific neck pain in taxi drivers: A single-blind, randomized controlled trial.

OBJECTIVES: Taxi drivers experience chronic neck pain owing to their posture while driving. The aim of this study was to investigate the effect of self-stretching exercises with kinesio taping on pain, stress, pressure pain threshold (PPT), disability, cervical range of motion (CROM) in this population. DESIGN: A single-blind, randomized controlled trial SETTING: Forty-three taxi drivers with nonspecific chronic nonspecific neck pain were randomly assigned to experimental (n = 22) and control (n = 21) groups. METHODS: In the experimental group, self-stretching exercises were performed 3 times a day, 5 days per week, for 4 weeks, with kinesio taping applied while driving. In the control group, only kinesio taping was applied while driving for 4 weeks. Pain intensity, stress intensity, PPT, neck disability, and CROM were assessed pre-intervention, post-intervention, and at 4 weeks post-intervention. RESULTS: Significant time and group interactions were observed in pain intensity at rest (p = 0.048) and while driving (p = 0.001). In the experimental group, the Pre - Post - Follow-up mean (95% CI) was 4.41 (4.14 to 4.68) - 3.82 (3.57 to 4.07) - 3.78 (3.55 to 3.99). In the control group, the Pre - Post - Follow-up mean (95% CI) was 4.29 (4.01 to 4.56) - 3.86 (3.60 to 4.11) - 4.05 (3.82 to 4.27) for pain at rest. In the experimental group, the Pre - Post - Follow-up mean (95% CI) was 4.91 (4.63 to 5.19) - 4.00 (3.76 to 4.24) - 3.69 (3.69 to 4.22), while in the control group, the Pre - Post - Follow-up mean (95% CI) was 4.81 (4.53 to 5.09) - 4.38 (4.13 to 4.63) - 4.57 (4.30 to 4.85) for pain while driving. PPT on the right (p = 0.029) and left (p < 0.001) sides, and neck disability (p = 0.001) also showed significant time and group interactions. NDI was not clinically significant based on the minimum clinically important difference. All CROM showed significant time and group interactions (flexion, p = 0.008; right lateral flexion, p = 0.009; left lateral flexion, p = 0.004; right rotation, p = 0.001; left rotation, p = 0.001), except for extension. CONCLUSION: This study showed that self-stretching exercises with kinesio taping provided benefits over kinesio taping alone on pain intensity, PPT, disability, and CROM in taxi drivers with nonspecific chronic neck pain. CLINICAL TRIAL REGISTRATION: This study registered with the Clinical Research Information Service (WHO International Clinical Trials Registry Platform) on September 22, 2020 (KCT0005406).

CHARMM-GUI Nanomaterial Modeler for Modeling and Simulation of Nanomaterial Systems.

Molecular modeling and simulation are invaluable tools for nanoscience that predict mechanical, physicochemical, and thermodynamic properties of nanomaterials and provide molecular-level insight into underlying mechanisms. However, building nanomaterial-containing systems remains challenging due to the lack of reliable and integrated cyberinfrastructures. Here we present Nanomaterial Modeler in CHARMM-GUI, a web-based cyberinfrastructure that provides an automated process to generate various nanomaterial models, associated topologies, and configuration files to perform state-of-the-art molecular dynamics simulations using most simulation packages. The nanomaterial models are based on the interface force field, one of the most reliable force fields (FFs). The transferability of nanomaterial models among the simulation programs was assessed by single-point energy calculations, which yielded 0.01% relative absolute energy differences for various surface models and equilibrium nanoparticle shapes. Three widely used Lennard-Jones (LJ) cutoff methods are employed to evaluate the compatibility of nanomaterial models with respect to conventional biomolecular FFs: simple truncation at r = 12 Å (12 cutoff), force-based switching over 10 to 12 Å (10-12 fsw), and LJ particle mesh Ewald with no cutoff (LJPME). The FF parameters with these LJ cutoff methods are extensively validated by reproducing structural, interfacial, and mechanical properties. We find that the computed density and surface energies are in good agreement with reported experimental results, although the simulation results increase in the following order: 10-12 fsw <12 cutoff < LJPME. Nanomaterials in which LJ interactions are a major component show relatively higher deviations (up to 4% in density and 8% in surface energy differences) compared with the experiment. Nanomaterial Modeler's capability is also demonstrated by generating complex systems of nanomaterial-biomolecule and nanomaterial-polymer interfaces with a combination of existing CHARMM-GUI modules. We hope that Nanomaterial Modeler can be used to carry out innovative nanomaterial modeling and simulations to acquire insight into the structure, dynamics, and underlying mechanisms of complex nanomaterial-containing systems.

Interaction mode of CIDE family proteins in fly: DREP1 and DREP3 acidic surfaces interact with DREP2 and DREP4 basic surfaces.

Cell death-inducing DNA fragmentation factor 45 (DFF45)-like effector (CIDE) domains were initially identified as protein interaction modules in apoptotic nucleases and are now known to form a highly conserved family with diverse functions that range from cell death to lipid homeostasis. In the fly, four CIDE domain-containing proteins (DFF-related protein [DREP]-1-4) and their functions, including interaction relationships, have been identified. In this study, we introduced and investigated acidic side-disrupted mutants of DREP1, DREP2, and DREP3. We discovered that the acidic surface patches of DREP1 and DREP3 are critical for the homo-dimerization. In addition, we found that the acidic surface sides of DREP1 and DREP3 interact with the basic surface sides of DREP2 and DREP4. Our current study provides clear evidence demonstrating the mechanism of the interactions between four DREP proteins in the fly.

Simultaneous Measurement of Serum Chemical Castration Agents and Testosterone Levels Using Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry.

Chemical castration involves administration of drugs to prevent pathological sexual behavior, reduce abnormal sexual drive and treat hormone-dependent cancers. Various drugs have been used for chemical castration; however, substantial interindividual variability and side effects are often observed. In this study, we proposed a useful monitoring method for the application of chemical castration agents using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS-MS). Testosterone, cyproterone acetate, medroxyprogesterone, goserelin acetate, leuprolide acetate and triptorelin acetate were analyzed by UPLC-MS-MS. The target drugs were extracted from serum samples by double protein precipitation using methanol. Testosterone-1,2-d2 and buserelin acetate were used as internal standards. Parameters of analytical performance were evaluated, including imprecision, linearity, ion suppression and detection capabilities. Testosterone measurements were compared with the results of immunoassays. Serum specimens from 51 subjects who underwent chemical castration were analyzed. All drugs and testosterone were well extracted and separated using our method. The method was essentially free from potential interferences and ion suppression. Within-run and between-run imprecision values were <15%. The lower limits of quantification were 0.125 and 0.5-1.0 ng/mL for testosterone and other drugs, respectively. Good correlations with pre-existing immunoassays for testosterone measurement were observed. Sera from subjects who underwent androgen deprivation therapy showed variable levels of drugs. We successfully developed a UPLC-MS-MS-based monitoring method for chemical castration. The performance of our method was generally acceptable. This method may provide a novel monitoring strategy for chemical castration to enhance expected effects while reducing unwanted side effects.

Effects of guanine bases at the central loop on stabilization of the quadruplex DNAs and their interactions with Meso-tetrakis(N-methylpyridium-4-yl)porphyrin.

The thermal stability of the G-quadruplex formed from the thrombin-binding aptamer, 5'G2T2G2TGTG2T2G2, in which the guanine (G) base at the central loop was replaced with an adenine (A) or inosine (I) base, was examined to determine the role of the central G base in stabilizing the quadruplex. Replacement of the central G base by the I base resulted in a slight decrease in thermal stability. On the other hand, the stability of the G-quadruplex decreased to a significant extent when it was replaced with the A base. The optimized structure of the G-quadruplex, which was obtained by a molecular dynamic simulation, showed that the carbonyl group of the C5 position of the central G base could form hydrogen bonds with the G1 amine group at the C7 position on the upper G-quartet. This formation of a hydrogen bond contributes to the stability of the G-quadruplex. The spectral property of meso-tetrakis(N-methylpyridium-4yl)porphyrin (TMPyP) associated with the G-quadruplex was characterized by a moderate red shift and hypochromism in the absorption spectrum, a positive CD signal, and two emission maxima in the fluorescence emission spectrum, suggesting that TMPyP binds at the exterior of the G-quadruplex. Spectral properties were slightly altered when the G base at the central loop was replaced with A or I, while the fluorescence decay times of TMPyP associated with the G-quadruplex were identical. Observed spectral properties removes the possibility of intercalation binding mode for TMPyP. TMPyP binds at the exterior of the quadruplex. Whether it stacks on the central loop or binds at the side of the quadruplex is unclear at this stage.

Conformations of adducts formed between the genotoxic benzo[a]pyrene-7,8-dione and 2'-deoxycytidine.

Benzo[a]pyrene-7,8-dione (BPQ) is formed by the activation of benzo[a]pyrene(B[a]P), which is an environmental toxic substance that is easily exposed in daily life, due to P450/epoxide hydrolase, and is a substance that induces DNA deformation by forming adducts with DNA. In this study, to investigate the form of bonding between BPQ and DNA, the structures of adducts between BPQ and 2'-deoxycytidine were examined. To examine BPQ-dC adduct conformation, geometry optimization of a total of 16 structural isomers was performed using the density functional theory method. In the structures of BPQ-dC adducts, for the cis-form, the angle between BPQ and dC is nearly perpendicular; but for the trans-form, the bending angle is small. The trans-form had a larger energy gap between ground state and excited state than the cis-form, and had a smaller HOMO-LUMO gap than the cis-form. Therefore, it was found that the trans-form absorbs stronger light and has higher reactivity than the cis-form. Molecular electrostatic potential was calculated and analyzed. The calculated ESP contour map shows the electrophilic and nucleophilic regions of the molecule.

Cosmomycin C inhibits signal transducer and activator of transcription 3 (STAT3) pathways in MDA-MB-468 breast cancer cell.

The signal transducer and activator of transcription 3 (STAT3) is constitutively activated in cancer cells. Therefore, blocking the aberrant activity of STAT3 in tumor cells is a validated therapeutic strategy. To discover novel inhibitors of STAT3 activity, we screened against microbial natural products using a dual-luciferase assay. Using the microbial metabolome library, we identified cosmomycin C (CosC), which was isolated from the mycelium extract of Streptomyces sp. KCTC19769, as a STAT3 pathway inhibitor. CosC inhibited STAT3 (Tyr705) phosphorylation and subsequent nuclear translocation in MDA-MB-468 breast cancer cells. CosC-mediated inhibition of STAT3 signaling pathway was confirmed by suppressed expression of STAT3 downstream target proteins including cyclin D1, Bcl-xL, survivin, Mcl-1, and VEGF in CosC-treated MDA-MB-468 cells. Flow cytometry showed that CosC caused accumulation in the G(0)-G(1) phase of the cell cycle and induced apoptosis via PARP cleavage and caspase-3 activation. Based on these findings, CosC may be a potential candidate for modulation of STAT3 pathway.