The role of piRNAs in predicting and prognosing in cancer: a focus on piRNA-823 (a systematic review and meta-analysis).

INTRODUCTION: This article examines the potential of using liquid biopsy with piRNAs to study cancer survival outcomes. While previous studies have explored the relationship between piRNA expression and cancer patient outcomes, a comprehensive investigation is still lacking. To address this gap, we conducted a systematic review and meta-analysis of existing literature. METHODS: We searched major online databases up to February 2024 to identify articles reporting on the role of piRNA in cancer patient survival outcomes. Our meta-analysis used a random-effects model to pool hazard ratios with 95% confidence intervals (CI) and assess the prognostic value of deregulated piRNA-823. For survival analysis, the Kaplan-Meier method and COX analysis were used. RESULTS: Out of 6104 articles screened, 20 met our inclusion criteria. Our analysis revealed that dysregulated piRNA expression is associated with cancer patient survival outcomes. Specifically, our meta-analysis found that overexpression of piR-823 is significantly linked with poorer overall survival in patients with colorectal cancer and renal cell cancer (HR: 3.82, 95% CI = [1.81, 8.04], I2 = 70%). CONCLUSION: Our findings suggest that various piRNAs may play a role in cancer survival outcomes and that piRNA-823 in particular holds promise as a prognostic biomarker for multiple human cancers. IMPLICATIONS FOR CANCER SURVIVORS: Our systematic review and meta-analysis of piRNA-823 has important implications for cancer survivors. Our findings suggest that piRNA-823 can be used as a prognostic biomarker for predicting cancer recurrence and survival rates. This information can help clinicians develop personalized treatment plans for cancer survivors, which can improve their quality of life and reduce the risk of recurrence.

Grafted Sertoli cells prevent neuronal cell death and memory loss induced by seizures.

Epilepsy significantly reduces the patient's quality of life, and we still need to develop new therapeutic approaches to control it. Transplantation of cells such as Sertoli cells (SCs), having a potent ability to release a variety of growth and immunoprotective substances, have made them a potential candidate to deal with neurological diseases like epilepsy. Hence, this study aims to evaluate whether SCs transplant effectively protects the hippocampus astrocytes and neurons to oppose seizure damage. For this purpose, the effects of bilateral intrahippocampal transplantation of SCs were investigated on the rats with the pentylenetetrazol (PTZ) induced seizure. After one-month, post-graft analysis was performed regarding behavior, immunohistopathology, and the distribution of the hippocampal cells. Our findings showed SCs transplantation reduced astrogliosis, astrocytes process length, the number of branches, and intersections distal to the soma of the hippocampus in the seizure group. In rats with grafted SCs, there was a drop in the hippocampal caspase-3 expression. Moreover, the SCs showed another protective impact, as shown by an improvement in pyramidal neurons' number and spatial distribution. The findings suggested that SCs transplantation can potently modify astrocytes' reactivation and inflammatory responses.

Successful use of Nicotiana tabacum hairy roots for the recombinant production of Cecropin A peptide.

Cecropin A, as an antimicrobial peptide (AMP), is possible to use in medical and agricultural fields as a new and safe biocontrol agent. Therefore, it is highly necessary to find a cost-effective and scalable approach to generate a large scale of it. In this research, the Agrobacterium rhizogenes strain ATCC 15834 was used to transfer the Cecropin A gene to the Nicotiana tabacum. After confirmation of transgenic hairy roots, the antibacterial activity of purified Cecropin A peptide was measured using the agar gel diffusion method. Successful transforming of Cecropin A was confirmed at the RNA and protein levels in hairy root cells using RT-PCR and enzyme-linked immunosorbent assay (ELISA), respectively. The highest Cecropin A amount was detected in line 4 of the transgenic lines using ELISA in comparison with the nontransgenic line. Subsequently, the antimicrobial activity of Cecropin A extracted from line 4 showed the highest inhibition activity against Aspergillus niger. Besides, this activity was stable against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Candida albicans pathogens after 7 days. The recombinant production of Cecropin A AMP had a yield of 63.81 µg/g of fresh weight. According to a significant yield, this system can be used to produce the Cecropin A peptide for pharmacological and food science applications.

Novel bioactive peptides of Achillea eriophora show anticancer and antioxidant activities.

Despite the limitations of current methods in cancer treatment, the use of bioactive peptides can be as an alternative to treat today. Therefore, isolation and relative purification of bioactive peptides was carried out form Achillea eriophora using a Sep-Pak C18 SPE cartridge and Amicon® Ultra Centrifugal Filters. The presence of desired peptides was checked using RP-HPLC and confirmed using LC-MS. The results of anticancer assay showed that the peptide mixture inhibits the growth of MCF-7 cancerous cell line with the values of IC50, GI50, and LC50 equal to 18.73 ± 0.22, 7.52 ± 0.15, and 56.73 ± 0.18 µg/mL, respectively. It also showed DPPH radical scavenging activity and cupric-ion reducing power with the IC50 value of 5.095 ± 0.23 and 63.3 ± 0.44 µg/mL, respectively. Although flavonoids were present in the sample along with the peptides, their amount was trivial (18.097 ± 1.36 µg/mL). Nevertheless, the results of the LC-MS showed mass-to-charge ratios of 301.17, 261.22, and 243.25, which was a dipeptide or tripeptide in compression to enzyme-digested BSA as a standard. In addition, SEM analysis of the purified peptide mixture showed that it kills the MCF-7 cancerous cell line by creating pores in the membrane. Therefore, it might be valuable to these peptides sequenced and be studied for physicochemical properties. Animal and clinical studies could help its application in drug development.

High concentration factor diffractive microlenses integrated with CMOS single-photon avalanche diode detector arrays for fill-factor improvement.

Large-format single-photon avalanche diode (SPAD) arrays often suffer from low fill-factors-the ratio of the active area to the overall pixel area. The detection efficiency of these detector arrays can be vastly increased with the integration of microlens arrays designed to concentrate incident light onto the active areas and may be refractive or diffractive in nature. The ability of diffractive optical elements (DOEs) to efficiently cover a square or rectangular pixel, combined with their capability of working as fast lenses (i.e., ∼f/3) makes them versatile and practical lens designs for use in sparse photon applications using microscale, large-format detector arrays. Binary-mask-based photolithography was employed to fabricate fast diffractive microlenses for two designs of 32×32 SPAD detector arrays, each design having a different pixel pitch and fill-factor. A spectral characterization of the lenses is performed, as well as analysis of performance under different illumination conditions from wide- to narrow-angle illumination (i.e., f/2 to f/22 optics). The performance of the microlenses presented exceeds previous designs in terms of both concentration factor (i.e., increase in light collection capability) and lens speed. Concentration factors greater than 33× are achieved for focal lengths in the substrate material as short as 190µm, representing a microlens f-number of 3.8 and providing a focal spot diameter of <4µm. These results were achieved while retaining an extremely high degree of performance uniformity across the 1024 devices in each case, which demonstrates the significant benefits to be gained by the implementation of DOEs as part of an integrated detector system using SPAD arrays with very small active areas.

Tamper-proof markings for the identification and traceability of high-value metal goods.

A customized UV nanosecond pulsed laser system has been developed for the fast generation of tamper-proof security markings on the surface of metals, such as stainless steel, nickel, brass, and nickel-chromium (Inconel) alloys. The markings in the form of reflective phase holographic structures are generated using a laser microsculpting process that involves laser-induced local melting and vaporization of the metal surface. The holographic structures are formed from an array of optically-smooth craters whose depth can be controlled with ± 25nm accuracy. In contrast to conventional security markings, e.g., engraved serial numbers, etched part numbers and embossed polymer holographic stickers, which are only attached to the metal products as an adhesive tape, the phase holographic structures are robust to local damage (e.g. scratches) and resistant to tampering because they are generated directly on the metal surface. This paper describes a novel laser-based process for security marking of high-value metal goods, investigates the optical performance of the holographic structures, and demonstrates their application to watches.

High resolution Shack-Hartmann sensor based on array of nanostructured GRIN lenses.

We present a novel method for the development of a micro lenslets hexagonal array. We use gradient index (GRIN) micro lenses where the variation of the refraction index is achieved with a structure of nanorods made of 2 types of glasses. To develop the GRIN micro lens array, we used a modified stack-and-draw technology which was originally applied for the fabrication of photonic crystal fibers. This approach results in a completely flat element that is easy to integrate with other optical components and can be effectively used in high refractive index medium as liquids. As a proof-of-concept of the method we present a hexagonal array of 469 GRIN micro lenses with a diameter of 20 µm each and 100% fill factor. The GRIN lens array is further used to build a Shack-Hartmann detector for measuring wavefront distortion. A 50 lens/mm sampling density is achieved.

Large elliptical nanostructured gradient-index microlens.

We demonstrate the feasibility of the development of a gradient-index elliptical microlens with a size of 75×125 µm using nanostructured glass technology. The gradient index is obtained by means of a discrete internal structure composed of two glasses with feature sizes much smaller than the wavelength of the incident light. A modified photonic crystal fiber-drawing technique is used for the lens fabrication. The elliptical shape of the lens is obtained by a novel final drawing stage where the spherically symmetric lens preform is drawn into an elliptical form by collapsing two large air holes placed in the preform during assembly. The effective focal lengths of 160 and 260 µm for the orthogonal axes are obtained experimentally for the fabricated lens, and show good agreement with those predicted by the effective medium theory and the full-wave beam propagation simulations.

Diffractive optics development using a modified stack-and-draw technique.

We present a novel method for the development of diffractive optical elements (DOEs). Unlike standard surface relief DOEs, the phase shift is introduced through a refractive index variation achieved by using different types of glass. For the fabrication of DOEs we use a modified stack-and-draw technique, originally developed for the fabrication of photonic crystal fibers, resulting in a completely flat element that is easy to integrate with other optical components. A proof-of-concept demonstration of the method is presented-a two-dimensional binary optical phase grating in the form of a square chessboard with a pixel size of 5 µm. Two types of glass are used: low refractive index silicate glass NC21 and high refractive index lead-silicate glass F2. The measured diffraction characteristics of the fabricated component are presented and it is shown numerically and experimentally that such a DOE can be used as a fiber interconnector that couples light from a small-core fiber into the several cores of a multicore fiber.

Fill-factor improvement of Si CMOS single-photon avalanche diode detector arrays by integration of diffractive microlens arrays.

Single-photon avalanche diode (SPAD) detector arrays generally suffer from having a low fill-factor, in which the photo-sensitive area of each pixel is small compared to the overall area of the pixel. This paper describes the integration of different configurations of high efficiency diffractive optical microlens arrays onto a 32 × 32 SPAD array, fabricated using a 0.35 µm CMOS technology process. The characterization of SPAD arrays with integrated microlens arrays is reported over the spectral range of 500-900 nm, and a range of f-numbers from f/2 to f/22. We report an average concentration factor of 15 measured for the entire SPAD array with integrated microlens array. The integrated SPAD and microlens array demonstrated a very high uniformity in overall efficiency.

Metasurface for characterization of the polarization state of light.

The miniaturization of measurement systems currently used to characterize the polarization state of light is limited by the bulky optical components used such as polarizers and waveplates. We propose and experimentally demonstrate a simple and compact approach to measure the ellipticity and handedness of the polarized light using an ultrathin (40 nm) gradient metasurface. A completely polarized light beam is decomposed into a left circularly polarized beam and a right circularly polarized beam, which are steered in two directions by the metasurface consisting of nanorods with spatially varying orientations. By measuring the intensities of the refracted light spots, the ellipticity and handedness of various incident polarization states are characterized at a range of wavelengths and used to determine the polarization information of the incident beam. To fully characterize the polarization state of light, an extra polarizer can be used to measure the polarization azimuth angle of the incident light.

Nanostructured gradient index microaxicons made by a modified stack and draw method.

We report the design and fabrication of nanostructured gradient index microaxicons suitable for integration with optical fibers. A structure with the effective refractive index decreasing linearly from the center to the edges (i.e., an axicon) was designed using a combination of a simulated annealing method and the effective medium theory. The design was verified numerically with beam propagation method simulations. The axicons were made by the modified stack and draw method and integrated with optical fibers. The optical properties of the fabricated elements were measured and showed good agreement with the numerical simulations. The fabricated axicons produced an extended line focus at a distance from about 70 to 160 µm from the lens facet with a minimum FWHM diameter of 8 µm at 90 µm. At smaller distances, an interference pattern is observed both in the experiment and in simulations, which is attributed to the uneven effective refractive index profile at the structure.

Broadband infrared supercontinuum generation in hexagonal-lattice tellurite photonic crystal fiber with dispersion optimized for pumping near 1560 nm: reply.

We respond to the comment submitted by Xian Feng on our recent Letter, Opt. Lett.38, 4679 (2013). The comment addressed the attenuation of our oxide tellurite glass labeled TWPN/I/6. We provide the originally measured absorbance spectrum of the glass and correct values of its mid-infrared attenuation.

Virus-like particles (VLPs): A promising platform for combating against Newcastle disease virus.

The global poultry industry plays a pivotal role in providing eggs and meat for human consumption. However, outbreaks of viral disease, especially Newcastle virus disease (NDV), within poultry farms have detrimental effects on various zootechnical parameters, such as body weight gain, feed intake, feed conversion ratio, as well as the quality of egg and meat production. Cases of vaccine failure have been reported in regions where highly pathogenic strains of NDV are prevalent. To tackle this challenge, virus-like particles (VLPs) have emerged as a potential solution. VLPs closely resemble natural viruses, offering biocompatibility and immune-stimulating properties that make them highly promising for therapeutic applications against NDV. Hence, this review emphasizes the significance of NDV and the need for effective treatments. The manuscript will contain several key aspects, starting with an exploration of the structure and properties of NDV. Subsequently, the paper will delve into the characteristics and benefits of VLPs compared to conventional drug delivery systems. A comprehensive analysis of VLPs as potential vaccine candidates targeting NDV will be presented, along with a discussion on strategies for loading cargo into these NDV-targeting VLPs. The review will also examine various expression systems utilized in the production of NDV-targeting VLPs. Additionally, the manuscript will address future prospects and challenges in the field, concluding with recommendations for further research.

Structure-guided design and cloning of peptide inhibitors targeting CDK9/cyclin T1 protein-protein interaction.

CDK9 (cyclin-dependent kinase 9) plays a significant role in numerous pathological conditions, such as HIV-1 infection and cancer. The interaction between CDK9 and cyclin T1 is crucial for maintaining the kinase's active state. Therefore, targeting this protein-protein interaction offers a promising strategy for inhibiting CDK9. In this study, we aimed to design and characterize a library of mutant peptides based on the binding region of cyclin T1 to CDK9. Using Osprey software, a total of 7,776 mutant peptides were generated. After conducting a comprehensive analysis, three peptides, namely, mp3 (RAADVEGQRKRRE), mp20 (RAATVEGQRKRRE), and mp29 (RAADVEGQDKRRE), were identified as promising inhibitors that possess the ability to bind to CDK9 with high affinity and exhibit low free binding energy. These peptides exhibited favorable safety profiles and displayed promising dynamic behaviors. Notably, our findings revealed that the mp3 and mp29 peptides interacted with a conserved sequence in CDK9 (residues 60-66). In addition, by designing the structure of potential peptides in the plasmid vector pET28a (+), we have been able to pave the way for facilitating the process of their recombinant production in an Escherichia coli expression system in future studies. Predictions indicated good solubility upon overexpression, further supporting their potential for downstream applications. While these results demonstrate the promise of the designed peptides as blockers of CDK9 with high affinity, additional experimental studies are required to validate their biological activity and assess their selectivity. Such investigations will provide valuable insights into their therapeutic potential and pave the way for the future development of peptide-based inhibitors targeting the CDK9-cyclin T1 complex.

Maximization of uricase production in a column bioreactor through response surface methodology-based optimization.

Uricase (EC 1.7.3.3) is an oxidoreductase enzyme that is widely exploited for diagnostic and treatment purposes in medicine. This study focuses on producing recombinant uricase fromE. coliBL21 in a bubble column bioreactor (BCB) and finding the optimal conditions for maximum uricase activity. The three most effective variables on uricase activity were selected through the Plackett-Burman design from eight different variables and were further optimized by the central composite design of the response surface methodology (RSM). The selected variables included the inoculum size (%v/v), isopropylß-d-1-thiogalactopyranoside (IPTG) concentration (mM) and the initial pH of the culture medium. The activity of uricase, the final optical density at 600 nm wavelength (OD600) and the final pH were considered as the responses of this optimization and were modeled. As a result, activity of 5.84 U·ml-1and a final OD600of 3.42 were obtained at optimum conditions of 3% v/v inoculum size, an IPTG concentration of 0.54 mM and a pH of 6.0. By purifying the obtained enzyme using a Ni-NTA agarose affinity chromatography column, 165 ± 1.5 mg uricase was obtained from a 600 ml cell culture. The results of this study show that BCBs can be a highly effective option for large-scale uricase production.

MicroRNA biosensors in lung cancer.

Lung cancer has been one of the leading causes of death over the past century. Unfortunately, the reliance on conventional methods to diagnose the phenotypic properties of tumors hinders early-stage cancer diagnosis. However, recent advancements in identifying disease-specific nucleotide biomarkers, particularly microRNAs, have brought us closer to early-stage detection. The roles of miR-155, miR-197, and miR-182 have been established in stage I lung cancer. Recent progress in synthesizing nanomaterials with higher conductivity has enhanced the diagnostic sensitivity of electrochemical biosensors, which can detect low concentrations of targeted biomarkers. Therefore, this review article focuses on exploring electrochemical biosensors based on microRNA in lung cancer.

Chronic Administration of Lisdexamfetamine Induces Apoptosis and Inflammation and Reduces Sperm Quality in Adult Male Rats.

Concerns have been raised about potentially irreversible brain damage and damage to the neuroendocrine system during development when treating attention-deficit/hyperactivity disorder with lisdexamfetamine (LDX), a norepinephrine dopamine reuptake inhibitor. This study aims to elucidate the potential adverse effects of LDX on the male reproductive system due to its widespread use and potential for abuse. In this study, adult male rats were randomized into control and LDX groups. Thirty milligrams per kilogram LDX was administered orally for 3 weeks. After isolation of epididymal spermatozoa, the rats were euthanized and testicular tissues were collected for stereological and molecular analyses. The LDX group showed a decrease in sperm motility and an increase in DNA fragmentation compared to the control group. There was also a dramatic decrease in testosterone in the LDX group. Testicular expression of caspase-3 and TNF-α was significantly increased in the LDX group. According to our findings, prolonged use of LDX leads to reduced sperm quality. It also induces apoptosis, inflammatory response, and pathological changes in the testicular tissue. What we have observed in this study is noteworthy but requires further investigation, particularly in people who use LDX over a longer period of time.

Two dimensional interferometric optical trapping of multiple particles and Escherichia coli bacterial cells using a lensed multicore fiber.

Two dimensional interferometric trapping of multiple microspheres and Escherichia coli has been demonstrated using a multicore fiber lensed with an electric arc fusion splicer. Light was coupled evenly into all four cores using a diffractive optical element. The visibility of the fringes and also the appearance of the lattice can be altered by rotating a half wave-plate. As a result the particles can be manipulated from one dimensional trapping to two dimensional trapping or a variety of different two dimensional arrangements. The ability to align bacterial populations has potential application for quorum sensing, floc and biofilm and, metabolic co-operation studies.

Broadband infrared supercontinuum generation in hexagonal-lattice tellurite photonic crystal fiber with dispersion optimized for pumping near 1560 nm.

We report on supercontinuum generation (SG) in a hexagonal lattice tellurite photonic crystal fiber (PCF). The fiber has a regular lattice with a lattice constant Λ = 2 µm, linear filling factor d/Λ = 0.75, and a solid core 2.7 µm in diameter. Dispersion, calculated from scanning electron microscope (SEM) image of drawn fiber, has zero dispersion wavelength (ZDW) at 1410 and 4236 nm with a maximum of 193 ps/nm/km at 2800 nm. Under pumping with 150 fs/36 nJ/1580 nm pulses, supercontinuum spectrum in a bandwidth from 800 nm to over 2500 nm was observed in a 2 cm long PCF sample, which is comparable to results reported for suspended core tellurite PCFs pumped at wavelengths over 1800 nm. Measured spectrum is analyzed numerically with good agreement, and observed spectral broadening is interpreted. To our best knowledge, tellurite glass, regular lattice PCFs for successful SG in this bandwidth have not been reported before.