Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers and cancer risk: an updated meta-analysis of observational studies.

Introduction: Debate on the association between the use of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) and the risk of developing cancer has been ongoing for decades. This study aimed to generate reliable results by analysing observational studies published in the decade after our last meta-analysis was conducted. Methods: We searched Embase and Medline databases on 21 January 2021 for cohort and case-control studies. Two researchers independently reviewed the literature and assessed the title and abstract of each publication. The I2 statistic used to evaluate the heterogeneity of the effect measures. Risk of bias was qualitatively assessed using the Newcastle-Ottawa scale. Results and discussion: We included an additional 16 cohort, 6 nested case-control, and 9 conventional case-control studies in the updated analysis. Overall HRs decreased, while overall relative risks increased. Conclusion: Our results show some protective effects through the hazard ratio and some detrimental effects through the relative risk. Large-scale investigations of cohorts followed up for decades are needed to clarify association. Plain Language Summary: Introduction: Two types of drug, angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), have been linked to the risk of developing cancer. We performed a meta-analysis by aggregating individual studies looking into the cancer risk of ACEIs and ARBs.Methods: We searched for articles on Embase and Medline databases until 21 January, 2021. Two researchers independently reviewed the literature and assessed the title and abstract of each publication.Results: Overall, the hazard ratio showed less than 1, while the relative risks showed higher than 1.Conclusion: Our results show some protective effects through the hazard ratio and some detrimental effects through the relative risk. Evidence supporting the risk of developing cancer is insufficient to prevent prescribing ACEIs or ARBs for patients with high blood pressure.

Feasibility study for combination of field-flow fractionation (FFF)-based separation of size-coded particle probes with amplified surface enhanced Raman scattering (SERS) tagging for simultaneous detection of multiple miRNAs.

We propose a new analytical scheme in which field-flow fractionation (FFF)-based separation of target-specific polystyrene (PS) particle probes of different sizes are incorporated with amplified surface-enhanced Raman scattering (SERS) tagging for the simultaneous and sensitive detection of multiple microRNAs (miRNAs). For multiplexed detection, PS particles of three different diameters (15, 10, 5 µm) were used for the size-coding, and a probe single stranded DNA (ssDNA) complementary to a target miRNA was conjugated on an intended PS particle. After binding of a target miRNA on PS probe, polyadenylation reaction was executed to generate a long tail composed of adenine (A) serving as a binding site to thymine (T) conjugated Au nanoparticles (T-AuNPs) to increase SERS intensity. The three size-coded PS probes bound with T-AuNPs were then separated in a FFF channel. With the observation of extinction-based fractograms, separation of three size-coded PS probes was clearly confirmed, thereby enabling of measuring three miRNAs simultaneously. Raman intensities of FFF fractions collected at the peak maximum of 15, 10 and 5 µm PS probes varied fairy quantitatively with the change of miRNA concentrations, and the reproducibility of measurement was acceptable. The proposed method is potentially useful for simultaneous detection of multiple miRNAs with high sensitivity.

Super-resolution imaging for monitoring cytoskeleton dynamics.

The cytoskeleton is a key cellular structure that is important in the control of cellular movement, structure, and sensing. To successfully image the individual cytoskeleton components, high resolution and super-resolution fluorescence imaging methods are needed. This review covers the three basic cytoskeletal elements and the relative benefits and drawbacks of fixed versus live cell imaging before moving on to recent studies using high resolution and super-resolution techniques. The techniques covered include the near-diffraction limited imaging methods of confocal microscopy and TIRF microscopy and the super-resolution fluorescence imaging methods of STORM, PALM, and STED.

Use of Multiple Peptide-Based SERS Probes Binding to Different Epitopes on a Protein Biomarker To Improve Detection Sensitivity.

We propose an analytical strategy to improve the sensitivity for detecting a protein biomarker through signal multiplication by manipulating multiple peptide-based surface-enhanced Raman scattering (SERS) probes to bind the biomarker. Protective antigen (PA) was used as an Anthrax biomarker in this study. For this purpose, five small peptides selective to various PA epitopes with different binding affinities were chosen and peptide-conjugated Au nanoparticle (AuNP) SERS probes were individually prepared using each peptide. Initially, five different SERS probes were separately used to detect PA and the sensitivities were compared. Next, the possibility of enhancing sensitivity by employing multiple SERS probes was examined. Rather than applying the probes simultaneously, which would induce competitive binding, each probe was added sequentially and an optimal probe-addition sequence was determined to provide maximal sensitivity. Finally, PA samples at seven different concentrations were measured with the optimal sequence. The limit of detection (LOD) was 0.1 aM, and the enhancement was more effective at lower PA concentrations. The proposed scheme can be further applicable to detect other protein biomarkers to diagnose various diseases.

Feasibility of asymmetrical flow field-flow fractionation as a method for detecting protective antigen by direct recognition of size-increased target-captured nanoprobes.

Asymmetrical flow field-flow fractionation (AF4) was evaluated as a potential analytical method for detection of a protective antigen (PA), an Anthrax biomarker. The scheme was based on the recognition of altered AF4 retention through the generation of the size-increased Au nanoparticle probes as a result of PA binding, in which a PA-selective peptide was conjugated on the probe surface. In the visible absorption-based AF4 fractograms, the band position shifted to a longer retention time as the PA concentration increased due to the presence of probe bound with PAs. The shift was insignificant when the concentration was relatively low at 84.3pM. To improve sensitivity, two separate probes conjugated with two different peptides able to bind on different PA epitopes were used together. The band shift then became distinguishable even at 84.3pM of PA sample. The formation of larger PA-probe inter-connected species using the dual-probe system was responsible for the enhanced band shift. In parallel, the feasibility of surface-enhanced Raman scattering (SERS) as a potential AF4 detection method was also evaluated. In the off-line SERS fractogram constructed using fractions collected during AF4 separation, a band shift was also observed for the 84.3pM PA sample, and the band intensity was higher when using the dual-probe system. The combination of AF4 and SERS is promising for the detection of PA and will become a potential tool if the reproducibility of SERS measurement is improved.

A Au nanoparticle-incorporated sponge as a versatile transmission surface-enhanced Raman scattering substrate.

We report a sponge-based transmission surface-enhanced Raman scattering (TSERS) substrate that combines the bulk sampling capabilities of a transmission measurement to improve the quantitative representation of sample concentration with several sponge properties useful for analysis such as fast sample uptake, easy sample enrichment, and a stable polymeric structure. Among nine commercially available sponges made of different materials, a melamine sponge was ultimately selected for this study because it provided the fastest sample uptake and a low background Raman signal. Simultaneously, the amino groups and three-nitrogen hybrid rings in its structure could easily hold Au nanoparticles (AuNPs) inside the sponge. AuNP-incorporated sponges (AuNP sponges) were prepared by simply soaking a melamine sponge in a AuNP solution; these sponges were initially used to measure 4-nitrobenzenethiol (4-NBT) samples with different concentrations in order to evaluate their ability as TSERS substrates. The intensities of the 4-NBT peaks clearly varied according to changes in the concentration, and the relative standard deviation (RSD) of the peak intensity estimated by the measurements of five independently prepared AuNP sponges was 10.0%. Sample enrichment was easily completed by repeated suctioning of the sample into the AuNP sponges followed by depletion of the solvent, so three-time enrichment doubled the intensity. Furthermore, paraquat samples were prepared in diverse matrices (de-ionized water, tap water, river water, and orange juice) and measured using the AuNP sponges. The paraquat peaks were clearly observed from these samples and their peak intensities became smaller with the increased compositional complexity of the matrices. Our overall results demonstrate that the TSERS sponge substrates are easy to prepare and practically versatile for SERS analysis of diverse samples.

Development of a particle-settling tolerant transmission Raman scheme for analysis of suspension samples.

We have demonstrated a simple and effective strategy, the so-called axial illumination scheme, that is able to obtain representative Raman spectra of suspension samples with minimal influence from internal particle settling. In a partially settled suspension sample, since particle concentrations at given points throughout the sample differ, the acquisition of Raman spectra representative of the entire sample composition is critically important for accurate quantitative analysis. The proposed scheme used axially irradiated laser radiation in the same or opposite direction of settling, thus allowing laser photons to migrate through the settling-induced particle-density gradient formed in the suspension and to widely interact with particles regardless of their settled locations. Therefore, transmitted Raman signals gathered opposite to the illumination could be more representative of the overall suspension composition even with partial settling. In this study, the performance of axial illumination schemes (TB (Top-to-Bottom) and BT (Bottom-to-Top) illumination) was evaluated for the determination of the aceclofenac (a non-steroidal anti-inflammatory drug) concentration in suspensions. Although the spectral features exhibited minute variations during settling, settling did not significantly degrade the accuracy of the concentration determination, thereby indicating effective acquisition of settling-tolerant Raman spectra. In addition, the characteristics of photon migration in a partially settled suspension sample were studied using a simulation based on Monte-Carlo method.

Wide area coverage Raman spectroscopy for reliable quantitative analysis and its applications.

This review summarizes recent studies to improve sample representation in Raman measurement by covering a large area of a sample in spectral collection. Three different schemes have been mainly investigated to fulfill the goal: (1) averaging of Raman spectra collected at many different locations on a sample, (2) rotation of a sample during spectral collection and (3) simultaneous wide area illumination (WAI) for spectral collection. The use of a wide area illumination scheme, simultaneously illuminating a laser over a large area for spectral acquisition without any further assistance such as sample rotation, has increased in diverse fields. Applications employing the WAI scheme in pharmaceutical, polymer/chemical/petrochemical and other areas are described in this review.

Inkjet-compatible single-component polydiacetylene precursors for thermochromic paper sensors.

Inkjet-printable diacetylene (DA) supramolecules, which can be dispersed in water without using additional surfactants, have been developed. The supramolecules are generated from DA monomers that contain bisurea groups, which are capable of forming hydrogen-bonding networks, and hydrophilic oligoethylene oxide moieties. Because of suitable size distribution and stability characteristics, the single DA component ink can be readily transferred to paper substrates by utilizing a common office inkjet printer. UV irradiation of the DA-printed paper results in generation of blue-colored polydiacetylene (PDA) images, which show reversible thermochromic transitions in specific temperature ranges. Inkjet-printed PDAs, in the format of a two-dimensional (2D) quick response (QR) code on a real parking ticket, serve as a dual anticounterfeiting system that combines easy decoding of the QR code and colorimetric PDA reversibility for validating the authenticity of the tickets. This single-component ink system has great potential for use in paper-based devices, temperature sensors, and anticounterfeiting barcodes.

Au nanoparticle-encapsulated hydrogel substrates for robust and reproducible SERS measurement.

A reliable and reproducible surface-enhanced Raman scattering (SERS) measurement utilizing Au nanoparticle-encapsulated hydrogels as a substrate has been demonstrated. A hydrogel matrix was adopted to: (i) take advantage of its excellent water uptake capacity for facile access of an analyte into the substrate and (ii) securely hold Au nanoparticles. Silica-coated Au (Au@SiO(2)) nanoparticles were initially prepared and uniquely used as an initiator as well as a cross-linker for the polymerization of acrylic acid to synthesize Au nanoparticle-encapsulated hydrogels. Then, the outer silica layer of the Au nanoparticles in the hydrogel was etched out using hydrofluoric acid (HF) to make it possible for an analyte to approach the surface of the Au nanoparticles for generation of the SERS signal. In parallel, locally occurring SERS signals over the hydrogel were integrated using a wide area illumination scheme capable of covering a large area to improve quantitative representation of analyte concentration. To evaluate reproducibility of the proposed method, 6 independent hydrogels were prepared every two months over one year and then Raman spectra of 2-naphthalenethiol (2-NAT) captured hydrogels were collected. The resulting SERS intensities of 2-NAT acquired at each concentration were reproducible and clearly increased according to the elevation of 2-NAT concentration.

Transmission Raman measurement directly through packed corn kernels to improve sample representation and accuracy of compositional analysis.

The potential of transmission Raman spectroscopy for direct analysis of packed granular samples, one of the most frequently encountered sample types in the field of non-destructive spectroscopic analysis, has been evaluated. For this purpose, transmission Raman spectra were collected by laser illumination through packed corn kernels to determine their protein concentration. Back-scattering Raman spectra of the same samples were also collected for comparison. Raman spectral features of the major kernel constituents were initially characterized, and Raman mapping over the whole kernel face was performed to investigate the inhomogeneous distribution of constituents in a kernel. Possible variations of transmission spectral features depending on the laser illumination on different locations of a kernel were investigated, since the orientation of kernels in the packing was essentially random. Rotation of kernel packing during spectral collection was helpful in improving the compositional representation of packed kernels. With partial least squares (PLS) regression, the protein concentrations were determined using both spectral collection methods and the resulting accuracies were compared. As a result, the transmission measurement provided a more accurate determination of protein concentration since it enabled deeper sampling across the packed kernels, leading to a better compositional representation of them. By contrast, in the back-scattering measurement, kernels on the top of the packing were mainly sampled for the spectral acquisition. Moreover, the back-scattering spectral feature, more weighted to constituents localized at the outer portion of a kernel, was short of representing the overall composition of a kernel.