Cardiovascular disease risk assessment through sensing the circulating microbiome with perovskite quantum dots leveraging deep learning models for bacterial species selection.

Perovskite quantum dots (PQDs) are novel nanomaterials wherein perovskites are used to formulate quantum dots (QDs). The present study utilizes the excellent fluorescence quantum yields of these nanomaterials to detect 16S rRNA of circulating microbiome for risk assessment of cardiovascular diseases (CVDs). A long short-term memory (LSTM) deep learning model was used to find the association of the circulating bacterial species with CVD risk, which showed the abundance of three different bacterial species (Bauldia litoralis (BL), Hymenobacter properus (HYM), and Virgisporangium myanmarense (VIG)). The observations suggested that the developed nano-sensor provides high sensitivity, selectivity, and applicability. The observed sensitivities for Bauldia litoralis, Hymenobacter properus, and Virgisporangium myanmarense were 0.606, 0.300, and 0.281 fg, respectively. The developed sensor eliminates the need for labelling, amplification, quantification, and biochemical assessments, which are more labour-intensive, time-consuming, and less reliable. Due to the rapid detection time, user-friendly nature, and stability, the proposed method has a significant advantage in facilitating point-of-care testing of CVDs in the future. This may also facilitate easy integration of the approach into various healthcare settings, making it accessible and valuable for resource-constrained environments.

Smart carbon-based sensors for the detection of non-coding RNAs associated with exposure to micro(nano)plastics: an artificial intelligence perspective.

Micro(nano)plastics (MNPs) are pervasive environmental pollutants that individuals eventually consume. Despite this, little is known about MNP's impact on public health. In this article, we assess the evidence for potentially harmful consequences of MNPs in the human body, concentrating on molecular toxicity and exposure routes. Since MNPs are present in various consumer products, foodstuffs, and the air we breathe, exposure can occur through ingestion, inhalation, and skin contact. MNPs exposure can cause mitochondrial oxidative stress, inflammatory lesions, and epigenetic modifications, releasing specific non-coding RNAs in circulation, which can be detected to diagnose non-communicable diseases. This article examines the most fascinating smart carbon-based nanobiosensors for detecting circulating non-coding RNAs (lncRNAs and microRNAs). Carbon-based smart nanomaterials offer many advantages over traditional methods, such as ease of use, sensitivity, specificity, and efficiency, for capturing non-coding RNAs. In particular, the synthetic methods, conjugation chemistries, doping, and in silico approach for the characterization of synthesized carbon nanodots and their adaptability to identify and measure non-coding RNAs associated with MNPs exposure is discussed. Furthermore, the article provides insights into the use of artificial intelligence tools for designing smart carbon nanomaterials.

Design and Fabrication of a Nanobiosensor for the Detection of Cell-Free Circulating miRNAS-LncRNAS-mRNAS Triad Grid.

The increased understanding of the competitive endogenous RNA (ceRNA) network in the onset and development of breast cancers has suggested their use as promising disease biomarkers. Keeping these RNAs as molecular targets, we designed and developed an optical nanobiosensor for specific detection of the miRNAs-LncRNAs-mRNAs triad grid in circulation. The sensor was formulated using three quantum dots (QDs), i.e., QD-705, QD-525, and GQDs. These QDs were surface-activated and modified with a target-specific probe. The results suggested the significant ability of the developed nanobiosensor to identify target RNAs in both isolated and plasma samples. Apart from the higher specificity and applicability, the assessment of the detection limit showed that the sensor could detect the target up to 1 fg concentration. After appropriate validation, the developed nanobiosensor might prove beneficial to characterizing and detecting aberrant disease-specific cell-free circulating miRNAs-lncRNAs-mRNAs.

Polycystic ovary syndrome: Current scenario and future insights.

Polycystic ovary syndrome (PCOS) prevails in approximately 33% of females of reproductive age globally. Although the root cause of the disease is unknown, attempts are made to clinically manage the disturbed hormone levels and symptoms arising due to hyperandrogenism, a hallmark of PCOS. This review presents detailed insights on the etiology, risk factors, current treatment strategies, and challenges therein. Medicinal agents currently in clinical trials and those in the development pipeline are emphasized. The significance of the inclusion of herbal supplements in PCOS and the benefits of improved lifestyle are also explained. Last, emerging therapeutic targets for treating PCOS are elaborated. The present review will assist the research fraternity working in the concerned domain to access significant knowledge associated with PCOS.

Carbon-Based Fluorescent Nano-Biosensors for the Detection of Cell-Free Circulating MicroRNAs.

Currently, non-communicable diseases (NCDs) have emerged as potential risks for humans due to adopting a sedentary lifestyle and inaccurate diagnoses. The early detection of NCDs using point-of-care technologies significantly decreases the burden and will be poised to transform clinical intervention and healthcare provision. An imbalance in the levels of circulating cell-free microRNAs (ccf-miRNA) has manifested in NCDs, which are passively released into the bloodstream or actively produced from cells, improving the efficacy of disease screening and providing enormous sensing potential. The effective sensing of ccf-miRNA continues to be a significant technical challenge, even though sophisticated equipment is needed to analyze readouts and expression patterns. Nanomaterials have come to light as a potential solution as they provide significant advantages over other widely used diagnostic techniques to measure miRNAs. Particularly, CNDs-based fluorescence nano-biosensors are of great interest. Owing to the excellent fluorescence characteristics of CNDs, developing such sensors for ccf-microRNAs has been much more accessible. Here, we have critically examined recent advancements in fluorescence-based CNDs biosensors, including tools and techniques used for manufacturing these biosensors. Green synthesis methods for scaling up high-quality, fluorescent CNDs from a natural source are discussed. The various surface modifications that help attach biomolecules to CNDs utilizing covalent conjugation techniques for multiple applications, including self-assembly, sensing, and imaging, are analyzed. The current review will be of particular interest to researchers interested in fluorescence-based biosensors, materials chemistry, nanomedicine, and related fields, as we focus on CNDs-based nano-biosensors for ccf-miRNAs detection applications in the medical field.

Nano-engineered vitamins as a potential epigenetic modifier against environmental air pollutants.

Air pollution has emerged as a serious threat to human health due to close association with spectrum of chronic ailments including cardiovascular disorders, respiratory diseases, nervous system dysfunctions, diabetes and cancer. Exposure to air-borne pollutants along with poor eating behaviours and inferior dietary quality irreversibly impacts epigenomic landscape, leading to aberrant transcriptional control of gene expression which is central to patho-physiology of non-communicable diseases. It is assumed that nutriepigenomic interventions such as vitamins can control such adverse effects through their immediate action on mitochondrial epigenomic-axis. Importantly, the exhaustive clinical utility of vitamins-interceded epigenetic synchronization is not well characterized. Therefore, improving the current limitations linked to stability and bioavailability issues in vitamin formulations is highly warranted. The present review not only sums up the available data on the role of vitamins as potential epigenetic modifiers but also discusses the importance of nano-engineered vitamins as potential epidrugs for dietary and pharmacological intervention to mitigate the long-term effects of air pollution toxicity.

Medicinal chemistry aspects and synthetic strategies of coumarin as aromatase inhibitors: an overview.

Coumarin is a bicyclic oxygen bearing heterocyclic scaffold formed by fusion of benzene with the pyrone ring. Because of its unique physicochemical characteristics and the ease with which it may be transformed into a wide range of functionalized coumarins during synthesis, coumarin provides a privileged scaffold for medicinal chemists. As a result, many coumarin derivatives have been developed, synthesized, and evaluated to target a variety of therapeutic domains, thereby making it an attractive template for designing novel anti-breast cancer compounds. The main culprit in estrogen overproduction in the estrogen-dependent breast cancer (EDBC), is the enzyme aromatase (AR), and it is thought to be a significant target for the effective treatment of EDBC. Considering coumarins versatility, this review presents a detailed overview of diverse study of aromatase as a target for coumarins. An overview of structure-activity relationship analysis of coumarin core is also included so as to summarize the desired pharmacophoric features essential for design and development of aromatase inhibitors (AIs) using coumarin core. Identification of key synthesis techniques that could aid researchers in designing and developing novel analogues with significant anti-breast cancer properties along with their mechanism of action have also been covered in the current review.

Bioanalytical Applications of Graphene Quantum Dots for Circulating Cell-Free Nucleic Acids: A Review.

Graphene quantum dots (GQDs) are carbonaceous nanodots that are natural crystalline semiconductors and range from 1 to 20 nm. The broad range of applications for GQDs is based on their unique physical and chemical properties. Compared to inorganic quantum dots, GQDs possess numerous advantages, including formidable biocompatibility, low intrinsic toxicity, excellent dispensability, hydrophilicity, and surface grating, thus making them promising materials for nanophotonic applications. Owing to their unique photonic compliant properties, such as superb solubility, robust chemical inertness, large specific surface area, superabundant surface conjugation sites, superior photostability, resistance to photobleaching, and nonblinking, GQDs have emerged as a novel class of probes for the detection of biomolecules and study of their molecular interactions. Here, we present a brief overview of GQDs, their advantages over quantum dots (QDs), various synthesis procedures, and different surface conjugation chemistries for detecting cell-free circulating nucleic acids (CNAs). With the prominent rise of liquid biopsy-based approaches for real-time detection of CNAs, GQDs-based strategies might be a step toward early diagnosis, prognosis, treatment monitoring, and outcome prediction of various non-communicable diseases, including cancers.

Graphene Quantum-Dot-Based Nanophotonic Approach for Targeted Detection of Long Noncoding RNAs in Circulation.

Recent progress in the field of nanophotonics has opened up novel avenues for developing nanomaterial-based biosensing systems, which can detect various disease-specific biomarkers, including long noncoding RNAs (lncRNAs) known to circulate in biological fluids. Herein, we designed and developed a nanophotonic approach for rapid and specific capture of lncRNAs using oligonucleotide-conjugated graphene quantum-dot-nanoconjugates. The method offers accurate identification of the target lncRNAs with high selectivity, despite the presence of other molecules in the given sample. The observations also pointed toward the high feasibility and simplicity of the method in the selective determination of lncRNAs. Overall, the approach has the potential of assessing lncRNA expression as a function of disease initiation and progression.

Surface-enhanced Raman scattering biosensors for detection of oncomiRs in breast cancer.

Surface-enhanced Raman scattering (SERS) has emerged as one of the most promising platforms for various biosensing applications. These sensing systems encompass the advantages of specificity, ultra-high sensitivity, stability, low cost, repeatability, and easy-to-use methods. Moreover, their ability to offer a molecular fingerprint and identify the target analyte at low levels make SERS a promising technique for detecting circulating cancer biomarkers with greater sensitivity and reliability. Among the various circulating biomolecules, oncomiRs are emerging as prominent biomarkers for the early screening of breast cancers (BCs). In this review, we provide a comprehensive understanding of different SERS-based biosensors and their application to identify BC-specific oncomiRs. We also discuss different SERS-based sensing strategies, nano-analytical frameworks, and challenges to be addressed for effective clinical translation.

In Silico Molecular Interaction Studies of Chitosan Polymer with Aromatase Inhibitor: Leads to Letrozole Nanoparticles for the Treatment of Breast Cancer.

BACKGROUND: It takes a lot more studies to evaluate the molecular interaction of nanoparticles with the drug, their drug delivery potential and release kinetics. Thus, we have taken in silico and in vitro approaches into account for the evaluation of the drug delivery ability of the chitosan nanoparticles. OBJECTIVE: The present work was aimed to study the interaction of chitosan nanoparticles with appropriate aromatase inhibitors using in silico tools. Further, synthesis and characterization of chitosan nanoparticles having optimal binding energy and affinity between drug and polymer in terms of size, encapsulation efficiency were carried out. METHODS: In the current study, molecular docking was used to map the molecular interactions and estimation of binding energy involved between the nanoparticles and the drug molecules in silico. Letrozole is used as a model cytotoxic agent currently being used clinically; hence Letrozole loaded chitosan nanoparticles were formulated and characterized using photomicroscope, particle size analyzer, scanning electron microscope and fourier transform infra-red spectroscopy. RESULTS: Letrozole had the second-highest binding affinity within the core of chitosan with MolDock (-102.470) and Re-rank (-81.084) scores. Further, it was investigated that formulated nanoparticles were having superior drug loading capacity and high encapsulation efficiency. In vitro drug release study exhibited prolonged release of the drug from chitosan nanoparticles. CONCLUSION: Results obtained from the in silico and in vitro studies suggest that Letrozole loaded nanoparticles are ideal for breast cancer treatment.

Polymeric Nanoparticles of Aromatase Inhibitors: A Comprehensive Review.

Being the second most frequent cancer, breast cancer is emerging worldwide with an alarming rate, specifically in post-menopausal women. Targeted drug delivery has been in the focus for the successful treatment of breast cancer by enhancing the drug delivery efficiency and reducing the systemic toxicity of drugs. Also, it eliminates the drawbacks associated with conventional chemotherapy, including neuropathy, memory loss, cardiotoxicity and low RBCs count. This review elaborates the polymeric nanoparticles based formulation approaches for selective and sustained delivery for effective cure of breast cancer. However, breast cancer, a life-threatening disease, is mostly caused because of estrogen, thus aromatase inhibitors and estrogen synthesis inhibitors could prevent chances of breast cancer. The disease is associated with drug resistance and some side effects, which could be easily eliminated by using novel therapeutic approaches. Aromatase inhibitors, when entrapped in nanoparticles, have shown sustained drug release, advocating themselves to be beneficial for the treatment of breast cancer.

Aromatase Inhibitors for the Treatment of Breast Cancer: A Journey from the Scratch.

BACKGROUND: Estrogens are essential for the growth of breast cancer in the case of premenopausal as well as in postmenopausal women. However, most of the breast cancer incidences are reported in postmenopausal women and the concurrent risk surges with an increase in age. Since the enzyme aromatase catalyses essential steps in estrogen biosynthesis, Aromatase Inhibitors (AIs) are effective targeted therapy in patients with Estrogen Receptor positive (ER+) breast cancer. AIs are more effective than Selective Estrogen Receptor Modulators (SERMs) because they block both the genomic and nongenomic activities of ER. Till date, first, second and third-generation AIs have been approved by the FDA. The third-generation AIs, viz. Letrozole, Anastrozole, Exemestane, are currently used in the standard treatment for postmenopausal breast cancer. METHODS: Data were collected from Medline, PubMed, Google Scholar, Science Direct through searching of keywords: 'aromatase', 'aromatase inhibitors', 'breast cancer', 'steroidal aromatase inhibitors', 'non-steroidal inhibitors' and 'generations of aromatase inhibitors'. RESULTS: In the current scenario of breast cancer chemotherapy, AIs are the most widely used agents which reveal optimum efficacy along with the least side effects. Keeping in view the prominence of AIs in breast cancer therapy, this review covered the detailed description of aromatase including its role in the biosynthesis of estrogen, biochemistry, gene expression, 3D-structure, and information of reported AIs along with their role in breast cancer treatment. CONCLUSION: AIs are the mainstream solution of the ER+ breast cancer treatment regimen with the continuous improvement of human understanding of the importance of a healthy life of women suffering from breast cancer.