Splice-Modulating Antisense Oligonucleotides as Therapeutics for Inherited Metabolic Diseases.

The last decade (2013-2023) has seen unprecedented successes in the clinical translation of therapeutic antisense oligonucleotides (ASOs). Eight such molecules have been granted marketing approval by the United States Food and Drug Administration (US FDA) during the decade, after the first ASO drug, fomivirsen, was approved much earlier, in 1998. Splice-modulating ASOs have also been developed for the therapy of inborn errors of metabolism (IEMs), due to their ability to redirect aberrant splicing caused by mutations, thus recovering the expression of normal transcripts, and correcting the deficiency of functional proteins. The feasibility of treating IEM patients with splice-switching ASOs has been supported by FDA permission (2018) of the first "N-of-1" study of milasen, an investigational ASO drug for Batten disease. Although for IEM, owing to the rarity of individual disease and/or pathogenic mutation, only a low number of patients may be treated by ASOs that specifically suppress the aberrant splicing pattern of mutant precursor mRNA (pre-mRNA), splice-switching ASOs represent superior individualized molecular therapeutics for IEM. In this work, we first summarize the ASO technology with respect to its mechanisms of action, chemical modifications of nucleotides, and rational design of modified oligonucleotides; following that, we precisely provide a review of the current understanding of developing splice-modulating ASO-based therapeutics for IEM. In the concluding section, we suggest potential ways to improve and/or optimize the development of ASOs targeting IEM.

Enhancing Structural and Thermal Properties of Poly(lactic acid) Using Graphene Oxide Filler and Anionic Surfactant Treatment.

Graphene has attracted extensive attention in various fields due to its intriguing properties. In this work, nanocomposite films based on poly(lactic acid) (PLA and PLLA) polymers filled with graphene oxide (GO) were developed. The impact of treating GO with the anionic surfactant dioctyl sulfosuccinate sodium salt (AOT) on the properties of the resulting nanocomposites was investigated. To determine the morphological, optical, and structural properties of the obtained materials, physicochemical analyses were performed, including scanning electron microscopy (SEM), atomic force microscopy (AFM), Fourier-transform infrared spectroscopy (FT-IR), and X-ray diffraction (XRD) analysis. Additionally, the thermal properties and wettability of neat polymers and nanocomposites were thoroughly investigated using differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and contact angle analysis. It was observed that GO was well dispersed throughout the PLA and PLLA matrix, leading to stronger interface bonding. The results demonstrate that the untreated and treated GO improved the crystallinity and thermal stability properties of the PLA and PLLA. However, the AOT-treated GO has significantly higher performance compared to the untreated GO in terms of crystallinity, melting temperature (increased by ~15 °C), and wettability (the contact angle decreased by ~30°). These findings reveal the high performance of the developed novel composite, which could be applied in tissue engineering as a scaffold.

Nanoparticles-assisted aptamer biosensing for the detection of environmental pathogens.

Given the importance of public health, it is crucial to develop quick, targeted, highly sensitive, and accurate technologies to monitor pathogenic microbes in response to the growing concerns of food and environmental safety. Although conventional approaches for microbiological detection are available, they are laborious, and often skill demanding. Therefore, such approaches are incompetent in the on-site or high-throughput assessment of pathogenic microbes. Numerous efforts have been made to develop biosensors that use nucleic acid aptamer as the biorecognition element, which would avoid the abovementioned limitations. Incorporating nanomaterials (NMs) into aptamer-based biosensors (aptasensors) improves their sensitivity and specificity, opening exciting possibilities for various applications, such as bioanalysis of food and environmental samples. Over the last decade, nanomaterial-conjugated aptasensors have seen a steadily rising demand. To this end, the main goal of this study is to demonstrate the novelty in the design of nanomaterial-conjugated aptasensors and how they can be used to detect different pathogenic microbes in water and food. The intent of this paper is to evaluate the cutting-edge techniques that have appeared in nano-aptasensors throughout the past few years, such as manufacturing procedures, analytical credibility, and sensing mechanisms. Additionally, the fundamental performance parameters of aptasensing techniques (such as detection limits, and sensing ranges response) were also used to evaluate their practical applicability. Finally, it is anticipated that this study will inspire innovative ideas and techniques for the construction and use of aptasensors for monitoring pathogenic microorganisms in food, drinks, recreational water, and wastewater.

An osteogenic, antibacterial, and anti-inflammatory nanocomposite hydrogel platform to accelerate bone reconstruction.

Fabricating an organic-inorganic nanocomposite hydrogel platform with antibacterial, anti-inflammatory, and osteoinductive properties that mimic bone extracellular matrix composition is decisive for guiding bone development in orthopedic practice. Despite significant progress in developing hydrogels for tissue repair, little attention has been paid to replicating the natural bone ECM microenvironments and addressing the importance of anti-inflammatory agents during osteogenesis. Herein, we developed ciprofloxacin and dexamethasone loaded strontium (Sr) and/or iron (Fe) substituted hydroxyapatite (HAp) nanomaterials precipitated in collagen (Col) to construct a multifunctional bioactive nanocomposite hydrogel platform to prevent inflammation and bacterial adhesion, leading to augmenting bone development in the defect site. The fabricated nanocomposite hydrogels (Sr:HAp-Col, Fe:HAp-Col, and Sr/Fe:HAp-Col) were physicochemically characterized and demonstrated high loading and prolonged drug release, and excellent antibacterial activity against Gram-positive and Gram-negative bacteria. In in vitro experiments, the Sr/Fe:HAp-Col sample exhibited enhanced bioactivity against the preosteoblast MC3T3-E1 cell line, with high alkaline phosphatase and bone-like inorganic calcium deposition, as well as increased gene expression of osteogenesis-related differentiation markers, including OPN, OCN, and RUNX2. Furthermore, in vivo experiments revealed that the Sr/Fe:HAp-Col matrix degraded over time by controlling the release of ions into the body, without causing acute inflammation at the implanted site or in the blood serum, or in the internal organs, including the heart, lungs, liver, and kidney of the Sprague-Dawley rat model. The micro-CT scan and histological examination showed high bone mineral density and more mature bone formation at the nanocomposite hydrogel implanted site associated with the ColMA hydrogel in the femur defect of the rat model. The strategy of applying collagen hydrogel supplemented with HAp to bone regeneration is promising due to its ability to mimic the natural bone ECM. Overall, the developed bioactive nanocomposite hydrogel may have great potential not only in bone regeneration but also in repairing nonunion-infected defects of other tissues.

Graphene Based Nanohybrid Aptasensors in Environmental Monitoring: Concepts, Design and Future Outlook.

In view of ever-increasing environmental pollution, there is an immediate requirement to promote cheap, multiplexed, sensitive and fast biosensing systems to monitor these pollutants or contaminants. Aptamers have shown numerous advantages in being used as molecular recognition elements in various biosensing devices. Graphene and graphene-based materials/nanohybrids combined with several detection methods exhibit great potential owing to their exceptional optical, electronic and physicochemical properties which can be employed extensively to monitor environmental contaminants. For environmental monitoring applications, aptamers have been successfully combined with graphene-based nanohybrids to produce a wide range of innovative methodologies. Aptamers are immobilized at the surface of graphene based nanohybrids via covalent and non-covalent strategies. This review highlights the design, working principle, recent developmental advances and applications of graphene based nanohybrid aptasensors (GNH-Apts) (since January 2014 to September 2021) with a special emphasis on two major signal-transduction methods, i.e., optical and electrochemical for the monitoring of pesticides, heavy metals, bacteria, antibiotics, and organic compounds from different environmental samples (e.g., water, soil and related). Lastly, the challenges confronted by scientists and the possible future outlook have also been addressed. It is expected that high-performance graphene-based nanohybrid aptasensors would find broad applications in the field of environmental monitoring.

Role of Drone Technology Helping in Alleviating the COVID-19 Pandemic.

The COVID-19 pandemic, caused by a new coronavirus, has affected economic and social standards as governments and healthcare regulatory agencies throughout the world expressed worry and explored harsh preventative measures to counteract the disease's spread and intensity. Several academics and experts are primarily concerned with halting the continuous spread of the unique virus. Social separation, the closing of borders, the avoidance of big gatherings, contactless transit, and quarantine are important methods. Multiple nations employ autonomous, digital, wireless, and other promising technologies to tackle this coronary pneumonia. This research examines a number of potential technologies, including unmanned aerial vehicles (UAVs), artificial intelligence (AI), blockchain, deep learning (DL), the Internet of Things (IoT), edge computing, and virtual reality (VR), in an effort to mitigate the danger of COVID-19. Due to their ability to transport food and medical supplies to a specific location, UAVs are currently being utilized as an innovative method to combat this illness. This research intends to examine the possibilities of UAVs in the context of the COVID-19 pandemic from several angles. UAVs offer intriguing options for delivering medical supplies, spraying disinfectants, broadcasting communications, conducting surveillance, inspecting, and screening patients for infection. This article examines the use of drones in healthcare as well as the advantages and disadvantages of strict adoption. Finally, challenges, opportunities, and future work are discussed to assist in adopting drone technology to tackle COVID-19-like diseases.

Progress in smartphone-enabled aptasensors.

Despite their high analytical performance, conventional analytical biosensor devices are usually difficult to handle, time-consuming, bulky and expensive. As a result, their applications remain restricted to resource-limited environments. In particular, the transportation of conventional analytical equipment is challenging for the proper in-situ point of need (PON)/point of care (POC) detection of biomolecules. In this context, smartphones, the most widely utilized cutting-edge mobile gadgets, continue to be a favored option because of their ease of portability and revolutionary sensing capabilities. On the other hand, aptamers are molecular recognition units consisting of nucleic acids with highly sensitive and selective recognition capabilities towards their respective targets. The coupling of smartphones with aptamers have led the development of advanced, user-friendly, portable, and cost-effective in-situ PON/POC biosensors for the detection of biomolecules. Such sensors are well-suited for a variety of applications, including food safety, environmental monitoring, and disease diagnostics. Herein, for the first time, achievements made between 2017 and 2022 in the concept and design of the smartphone-enabled aptasensors for biosensing applications are reviewed. The review covers different fabrication strategies and the discussion of several operating systems, underlying programs, and related software. At the end, the important merits, challenges, and future prospects of smart phone-driven aptasensors are presented. This report intends to assist scientists and engineers in comprehending the fabrication of smartphone-based aptasensors and their underlying sensing principles, as well as stimulating the future developments in the direction of affordable, portable, simple, and readily available sensing devices.

Heavy Metal Ions Detection Using Nanomaterials-Based Aptasensors.

Heavy metals ions as metallic pollutants are a growing global issue due to their adverse effects on the aquatic ecosystem, and human health. Unfortunately, conventional detection methods such as atomic absorption spectrometry exhibit a relatively low limit of detection and hold numerous disadvantages, and therefore, the development of an efficient method for in-situ and real-time detection of heavy metal residues is of great importance. The aptamer-based sensors offer distinct advantages over antibodies and emerged as a robust sensing platform against various heavy metals due to their high sensitivity, ease of production, simple operations, excellent specificity, better stability, low immunogenicity, and cost-effectiveness. The nucleic acid aptamers in conjugation with nanomaterials can bind to the metal ions with good specificity/selectivity and can be used for on-site monitoring of metal ion residues. This review aimed to provide background information about nanomaterials-based aptasensor, recent advancements in aptamer conjunction on nanomaterials surface, the role of nanomaterials in improving signal transduction, recent progress of nanomaterials-based aptasening procedures (from 2010 to 2022), and future perspectives toward the practical applications of nanomaterials-based aptasensors against hazardous metal ions for food safety and environmental monitoring.

An electrochemical aptasensor with N protein binding aptamer-complementary oligonucleotide as probe for ultra-sensitive detection of COVID-19.

The emergence of the COVID-19 epidemic has affected the lives of hundreds of millions of people globally. There is no doubt that the development of fast and sensitive detection methods is crucial while the worldwide effective vaccination programs are miles away from actualization. In this study, we have reported an electrochemical N protein aptamer sensor with complementary oligonucleotide as probe for the specific detection of COVID-19. The electrochemical aptasensor was prepared by fixing the double-stranded DNA hybrid obtained by the hybridization of N protein aptamer and its Fc-labeled complementary strand on the surface of a gold electrode. After incubation with the target, the aptamer dissociated from the labeled complementary DNA oligonucleotide hybrid to preferentially bind with N protein in the solution. The concentration of N protein was measured by detecting the changes in electrochemical current signals induced by the conformational transformation of the complementary DNA oligonucleotide left on the electrode surface. The sensor had a linear relationship between the logarithm of the N protein concentration from 10 fM to 100 nM (ΔIp = 0.098 log CN protein/fM - 0.08433, R2 = 0.99), and the detection limitation was 1 fM (S/N = 3). The electrochemical aptamer sensor was applied to test the spiked concentrations of throat swabs and blood samples from three volunteers, and the obtained results proved that the sensor has great potentials for the early detection of COVID-19 in patients.

Advances in Gold Nanoparticles-Based Colorimetric Aptasensors for the Detection of Antibiotics: An Overview of the Past Decade.

Misuse of antibiotics has recently been considered a global issue because of its harmful effects on human health. Since conventional methods have numerous limitations, it is necessary to develop fast, simple, sensitive, and reproducible methods for the detection of antibiotics. Among numerous recently developed methods, aptasensors are fascinating because of their good specificity, sensitivity and selectivity. These kinds of biosensors combining aptamer with colorimetric applications of gold nanoparticles to recognize small molecules are becoming more popular owing to their advantageous features, for example, low cost, ease of use, on-site analysis ability using naked eye and no prerequisite for modern equipment. In this review, we have highlighted the recent advances and working principle of gold nanoparticles based colorimetric aptasensors as promising methods for antibiotics detection in different food and environmental samples (2011-2020). Furthermore, possible advantages and disadvantages have also been summarized for these methods. Finally, the recent challenges, outlook, and promising future perspectives for developing novel aptasensors are also considered.

Advances in Optical Aptasensors for Early Detection and Diagnosis of Various Cancer Types.

Cancer is a life-threatening concern worldwide. Sensitive and early-stage diagnostics of different cancer types can make it possible for patients to get through the best available treatment options to combat this menace. Among several new detection methods, aptamer-based biosensors (aptasensors) have recently shown promising results in terms of sensitivity, identification, or detection of either cancerous cells or the associated biomarkers. In this mini-review, we have summarized the most recent (2016-2020) developments in different approaches belonging to optical aptasensor technologies being widely employed for their simple operation, sensitivity, and early cancer diagnostics. Finally, we shed some light on limitations, advantages, and current challenges of aptasensors in clinical diagnostics, and we elaborated on some future perspectives.

Role of receptor tyrosine kinases mediated signal transduction pathways in tumor growth and angiogenesis-New insight and futuristic vision.

In the past two decades, significant progress has been made in the past two decades towards the understanding of the basic mechanisms underlying cancer growth and angiogenesis. In this context, receptor tyrosine kinases (RTKs) play a pivotal role in cell proliferation, differentiation, growth, motility, invasion, and angiogenesis, all of which contribute to tumor growth and progression. Mutations in RTKs lead to abnormal signal transductions in several pathways such as Ras-Raf, MEK-MAPK, PI3K-AKT and mTOR pathways, affecting a wide range of biological functions including cell proliferation, survival, migration and vascular permeability. Increasing evidence demonstrates that multiple kinases are involved in angiogenesis including RTKs such as vascular endothelial growth factor, platelet derived growth factor, epidermal growth factor, insulin-like growth factor-1, macrophage colony-stimulating factor, nerve growth factor, fibroblast growth factor, Hepatocyte Growth factor, Tie 1 & 2, Tek, Flt-3, Flt-4 and Eph receptors. Overactivation of RTKs and its downstream regulation is implicated in tumor initiation and angiogenesis, representing one of the hallmarks of cancer. This review discusses the role of RTKs, PI3K, and mTOR, their involvement, and their implication in pro-oncogenic cellular processes and angiogenesis with effective approaches and newly approved drugs to inhibit their unrestrained action.