Role of MicroRNA-21 in Prostate Cancer Progression and Metastasis: Molecular Mechanisms to Therapeutic Targets.

The role of noncoding RNA has made remarkable progress in understanding progression, metastasis, and metastatic castration-resistant prostate cancer (mCRPC). A better understanding of the miRNAs has enhanced our knowledge of their targeting mainly at the therapy level in solid tumors, such as prostate cancer (PCa). microRNAs (miRNAs) belong to a class of endogenous RNA that deficit encoded proteins. Therefore, the role of miRNAs has been well-coined in the progression and development of PCa. miR-21 has a dual nature in its work both as a tumor suppressor and oncogenic role, but most of the recent studies showed that miR-21 is a tumor promoter and also is involved in castration-resistant prostate cancer (CRPC). Upregulation of miR-21 suppresses programmed cell death and inducing metastasis and castration resistant in PCa. miR-21 is involved in the different stages, such as proliferation, angiogenesis, migration, and invasion, and plays an important role in the progression, metastasis, and advanced stages of PCa. Recently, various studies directly linked the role of high levels of miR-21 with a poor therapeutic response in the patient of PCa. In the present review, we have explained the molecular mechanisms/pathways of miR-21 in PCa progression, metastasis, and castration resistant and summarized the role of miR-21 in diagnosis and therapeutic levels in PCa. In addition, we have spotlighted the recent therapeutic strategies for targeting different stages of PCa.

Impact of Plasmonic and Dielectric Substrates on the Whispering-Gallery Modes in Self-Assembled Fluorescent Semiconductor Polymer Microspheres.

In this work, the impact of metallic and dielectric conducting substrates, gold and indium tin oxide (ITO)-coated glass, on the whispering gallery modes (WGMs) of semiconductor π-conjugated polymer microspheres is investigated. Hyperspectral mapping was performed to obtain the excitation-position-dependent emission spectra of the microspheres. Substrate-dependent quenching of WGMs sensitive to mode polarization was observed and explained. On a glass substrate, both transverse-electric (TE) and transverse-magnetic (TM) WGMs are quenched due to frustrated total internal reflection. On a gold substrate, however, only the TM WGMs are allowed in symmetry to leak into surface plasmons. An atomically flat gold substrate with subwavelength slits was used to experimentally verify the leakage of WGMs into the surface plasmon polaritons (SPPs). This work provides insight into the damping mechanisms of WGMs in microspheres on metallic and dielectric substrates.

Insights into the mechanisms of diabetic wounds: pathophysiology, molecular targets, and treatment strategies through conventional and alternative therapies.

Diabetes mellitus is a prevalent cause of mortality worldwide and can lead to several secondary issues, including DWs, which are caused by hyperglycemia, diabetic neuropathy, anemia, and ischemia. Roughly 15% of diabetic patient's experience complications related to DWs, with 25% at risk of lower limb amputations. A conventional management protocol is currently used for treating diabetic foot syndrome, which involves therapy using various substances, such as bFGF, pDGF, VEGF, EGF, IGF-I, TGF-ß, skin substitutes, cytokine stimulators, cytokine inhibitors, MMPs inhibitors, gene and stem cell therapies, ECM, and angiogenesis stimulators. The protocol also includes wound cleaning, laser therapy, antibiotics, skin substitutes, HOTC therapy, and removing dead tissue. It has been observed that treatment with numerous plants and their active constituents, including Globularia Arabica, Rhus coriaria L., Neolamarckia cadamba, Olea europaea, Salvia kronenburgii, Moringa oleifera, Syzygium aromaticum, Combretum molle, and Myrtus communis, has been found to promote wound healing, reduce inflammation, stimulate angiogenesis, and cytokines production, increase growth factors production, promote keratinocyte production, and encourage fibroblast proliferation. These therapies may also reduce the need for amputations. However, there is still limited information on how to prevent and manage DWs, and further research is needed to fully understand the role of alternative treatments in managing complications of DWs. The conventional management protocol for treating diabetic foot syndrome can be expensive and may cause adverse side effects. Alternative therapies, such as medicinal plants and green synthesis of nano-formulations, may provide efficient and affordable treatments for DWs.

Phytochemical Profiling and Pharmacological Evaluation of Leaf Extracts of Ruellia tuberosa L.: An In Vitro and In Silico Approach.

The present study was designed to appraise the photoprotective, antioxidant, and antibacterial bioactivities of Ruellia tuberosa leaves extracts (RtPE, RtChl, RtEA, RtAc, RtMe, and RtHMe). The results showed that, RtHMe extracts of R. tuberosa was rich in total phenolic content, i. e., 1.60 mgGAE/g dry extract, while highest total flavonoid content was found in RtAc extract, i. e., 0.40 mgQE/g. RtMe showed effective antioxidant activity (%RSA: 58.16) at the concentration of 120 µL. RtMe, RtEA and RtHMe exhibited effective in vitro antibacterial activity against Gram-negative bacteria (E. coli). In silico docking studies revealed that paucifloside (-11.743 kcal/mol), indole-3-carboxaldehyde (-7.519 kcal/mol), nuomioside (-7.275 kcal/mol), isocassifolioside (-6.992 kcal/mol) showed best docking score against PDB ID 2EX8 [penicillin binding protein 4 (dacB) from Escherichia coli, complexed with penicillin-G], PDB ID 6CQA (E. coli dihydrofolate reductase protein complexed with inhibitor AMPQD), PDB ID 2Y2I [Penicillin-binding protein 1B in complex with an alkyl boronate (ZA3)] and PDB ID 2OLV (from S. aureus), respectively. Docked phytochemicals also showed good drug likeness properties.

Electrochemical biosensors based on in situ grown carbon nanotubes on gold microelectrode array fabricated on glass substrate for glucose determination.

A highly sensitive electrochemical sensor is reported for glucose detection using carbon nanotubes grown in situ at low temperatures on photolithographically defined gold microelectrode arrays printed on a glass substrate (CNTs/Au MEA). One of the main advantages of the present design is its potential to monitor 64 samples individually for the detection of glucose. The selectivity of the fabricated MEA towards glucose detection is achieved via modification of CNTs/Au MEA by immobilizing glucose oxidase (GOx) enzyme in the matrix of poly (paraphenylenediamine) (GOx/poly (p-PDA)/CNTs/Au MEA). The electrocatalytic and electrochemical responses of the proposed sensing platform towards glucose determination were examined via cyclic voltammetry and electrochemical impedance spectroscopy. The developed impedimetric biosensor exhibits a good linear response towards glucose detection, i.e., 0.2-27.5 µM concentration range with sensitivity and detection limits of 168.03 kΩ-1 M-1 and 0.2 ± 0.0014 µM, respectively. The proposed glucose biosensor shows excellent reproducibility, good anti-interference property, and was successfully tested in blood serum samples. Further, the applicability of the proposed sensor was successfully validated through HPLC. These results supported the viability of using such devices for the simultaneous detection of multiple electroactive biomolecules of physiological relevance.

Expand and Shrink: Federated Learning with Unlabeled Data Using Clustering.

The amalgamation of the Internet of Things (IoT) and federated learning (FL) is leading the next generation of data usage due to the possibility of deep learning with data privacy preservation. The FL architecture currently assumes labeled data samples from a client for supervised classification, which is unrealistic. Most research works in the literature focus on local training, update receiving, and global model updates. However, by principle, the labeling must be performed on the client side because the data samples cannot leave the source under the FL principle. In the literature, a few works have proposed methods for unlabeled data for FL using "class-prior probabilities" or "pseudo-labeling". However, these methods make either unrealistic or uncommon assumptions, such as knowing class-prior probabilities are impractical or unavailable for each classification task and even more challenging in the IoT ecosystem. Considering these limitations, we explored the possibility of performing federated learning with unlabeled data by providing a clustering-based method of labeling the sample before training or federation. The proposed work will be suitable for every type of classification task. We performed different experiments on the client by varying the labeled data ratio, the number of clusters, and the client participation ratio. We achieved accuracy rates of 87% and 90% by using 0.01 and 0.03 of the truth labels, respectively.

Nonlinear Optical Signal Generation Mediated by a Plasmonic Azimuthally Chirped Grating.

Plasmonic gratings are simple and effective platforms for nonlinear signal generation since they provide a well-defined momentum for photon-plasmon coupling and local hot spots for frequency conversion. Here, a plasmonic azimuthally chirped grating (ACG), which provides spatially resolved broadband momentum for photon-plasmon coupling, was exploited to investigate the plasmonic enhancement effect in two nonlinear optical processes, namely two-photon photoluminescence (TPPL) and second harmonic generation (SHG). The spatial distributions of the nonlinear signals were determined experimentally by hyperspectral mapping with ultrashort pulsed excitation. The experimental spatial distributions of nonlinear signals agree very well with the analytical prediction based on photon-plasmon coupling with the momentum of the ACG, revealing the "antenna" function of the grating in plasmonic nonlinear signal generation. This work highlights the importance of the antenna effect of the gratings for nonlinear signal generation and provides insight into the enhancement mechanism of plasmonic gratings in addition to local hot spot engineering.

Signal and noise analysis for chiral structured illumination microscopy.

Recently, chiral structured illumination microscopy has been proposed to image fluorescent chiral domains at sub-wavelength resolution. Chiral structured illumination microscopy is based on the combination of structured illumination microscopy, fluorescence-detected circular dichroism, and optical chirality engineering. Since circular dichroism of natural chiral molecules is typically weak, the differential fluorescence is also weak and can be easily buried by the noise, hampering the fidelity of the reconstructed images. In this work, we systematically study the impact of the noise on the quality and resolution of chiral domain images obtained by chiral SIM. We analytically describe the signal-to-noise ratio of the reconstructed chiral SIM image in the Fourier domain and verify our theoretical calculations with numerical demonstrations. Accordingly, we discuss the feasibility of chiral SIM in different experimental scenarios and propose possible strategies to enhance the signal-to-noise ratio for samples with weak circular dichroism.

Structured illumination microscopy for simultaneous imaging of achiral and chiral domains.

We propose double structured illumination microscopy (SIM) method, which enables simultaneous imaging of achiral and chiral domains at sub-wavelength resolution. In double SIM, the illumination field is spatially structured both in the intensity and optical chirality so that moiré effects can be concurrently generated on the achiral and chiral fluorescent domains of a sample. This allows for down-modulating the high spatial frequency of both domains at the same time and thus provides sub-wavelength details after image reconstruction. We introduce the working principle of double SIM and theoretically demonstrate the feasibility of this method using different kinds of synthetic samples.

Patents on PARP-1 Inhibitors for the Management of Cancer from 2017-2023.

BACKGROUND: There are eighteen members of the Poly (ADP-ribose) polymerases (PARPs) family, which oversee various cellular processes such as maintaining the integrity of the genome, regulating transcription, cell cycle progression, initiating the DNA damage response, and apoptosis. PARP1 is an essential member of the PARP family and plays a crucial role in repairing single-strand breaks in eukaryotic cells through a process called BER (base excision repair). It is the most extensively studied and commonly found member of this family. AREA COVERED: This article discusses the advancements in developing PARP inhibitors for human cancers. It covers the discovery of new PARP1 inhibitors with chemical classification that selectively target multiple areas using cancer models in vitro and in vivo and evaluates them critically. The focus is on patents that have been published from 2017 to 2023, except tankyrase inhibitors. EXPERT OPINION: PARP1 inhibitors were developed by various companies and academic groups from the 1990s to enhance the effectiveness of chemo and radiotherapy. However, their progress was hindered due to their severe toxicity when combined with these treatments. Therefore, on finding PARP1 inhibitors that can amplify the ability of chemotherapy agents to kill tumors while causing minimal toxicity, these substances can either be used alone as part of the synthetic lethality approach or in conjunction with radiotherapy or chemotherapy, resulting in a mutually beneficial outcome.

Medicinal chemistry aspects of uracil containing dUTPase inhibitors targeting colorectal cancer.

Deoxyuridine-5'-triphosphate nucleotidohydrolase (dUTPase), a vital enzyme in pyrimidine metabolism, is a prime target for treating colorectal cancer. Uracil shares structural traits with DNA/RNA bases, prompting exploration by medicinal chemists for pharmacological modifications. Some existing drugs, including thymidylate synthase (TS) and dUTPase inhibitors, incorporate uracil moieties. These derivatives hinder crucial cell proliferation pathways encompassing TS, dUTPases, dihydropyrimidine dehydrogenase, and uracil-DNA glycosylase. This review compiles uracil derivatives that have served as dUTPase inhibitors across various organisms, forming a library for targeting human dUTPase. Insights into their structural requisites for human applications and comparative analyses of binding pockets are provided for analyzing the compounds against human dUTPase.

Current insights and molecular docking studies of HIV-1 reverse transcriptase inhibitors.

Human immunodeficiency virus (HIV) causes acquired immunodeficiency syndrome (AIDS), a lethal disease that is prevalent worldwide. According to the Joint United Nations Programme on HIV/AIDS (UNAIDS) data, 38.4 million people worldwide were living with HIV in 2021. Viral reverse transcriptase (RT) is an excellent target for drug intervention. Nucleoside reverse transcriptase inhibitors (NRTIs) were the first class of approved antiretroviral drugs. Later, a new type of non-nucleoside reverse transcriptase inhibitors (NNRTIs) were approved as anti-HIV drugs. Zidovudine, didanosine, and stavudine are FDA-approved NRTIs, while nevirapine, efavirenz, and delavirdine are FDA-approved NNRTIs. Several agents are in clinical trials, including apricitabine, racivir, elvucitabine, doravirine, dapivirine, and elsulfavirine. This review addresses HIV-1 structure, replication cycle, reverse transcription, and HIV drug targets. This study focuses on NRTIs and NNRTIs, their binding sites, mechanisms of action, FDA-approved drugs and drugs in clinical trials, their resistance and adverse effects, their molecular docking studies, and highly active antiretroviral therapy (HAART).

Design, Virtual Screening, Molecular Docking, ADME and Cytotoxicity Studies of 1,3,5-Triazine Containing Heterocyclic Scaffolds as Selective BRAF Monomeric, Homo and Heterodimeric Inhibitors.

BACKGROUND: v-RAF murine sarcoma viral homolog B1 (BRAF) is one of the most frequently mutated kinases in human cancers. BRAF exhibits three classes of mutations: Class I monomeric mutants (BRAFV600), class II BRAF homodimer mutants (non-V600), and class III BRAF heterodimers (non-V600). METHOD: In this manuscript, the protein-ligand interaction site of all three mutants: BRAF monomer, BRAF homodimer BRAF2:14-3-32, and BRAF heterodimer BRAF:14-3-32:MEK (Mitogen extracellular Kinase) has been discussed. FDA-approved drugs still have limitations against all three classes of mutants, especially against the second and third classes. Using the DesPot grid model, 1114 new compounds were designed. Using virtual screening, the three PDB Ids 4XV2 for monomers, 7MFF for homodimers, and 4MNE for heterodimers were used for 1114 newly designed compounds. RESULT: Dabrafenib, encorafenib, sorafenib and vemurafenib were included as standard drugs. The top 10 hit molecules were identified for each protein. Additional binding studies were performed using molecular docking studies on the protein-ligand site of each PDB identifier. Absorption, distribution, metabolism, excretion (ADME) and toxicity studies were also performed. CONCLUSION: It was identified that top-hit molecules had better binding and interaction activity than standard in all three classes of mutants.

Phytoconstituents as modulators of NF-κB signalling: Investigating therapeutic potential for diabetic wound healing.

The NF-κB pathway plays a pivotal role in impeding the diabetic wound healing process, contributing to prolonged inflammation, diminished angiogenesis, and reduced proliferation. In contrast to modern synthetic therapies, naturally occurring phytoconstituents are well-studied inhibitors of the NF-κB pathway that are now attracting increased attention in the context of diabetic wound healing because of lower toxicity, better safety and efficacy, and cost-effectiveness. This study explores recent research on phytoconstituent-based therapies and delve into their action mechanisms targeting the NF-κB pathway and potential for assisting effective healing of diabetic wounds. For this purpose, we have carried out surveys of recent literature and analyzed studies from prominent databases such as Science Direct, Scopus, PubMed, Google Scholar, EMBASE, and Web of Science. The classification of phytoconstituents into various categorie such as: alkaloids, triterpenoids, phenolics, polyphenols, flavonoids, monoterpene glycosides, naphthoquinones and tocopherols. Noteworthy phytoconstituents, including Neferine, Plumbagin, Boswellic acid, Genistein, Luteolin, Kirenol, Rutin, Vicenin-2, Gamma-tocopherol, Icariin, Resveratrol, Mangiferin, Betulinic acid, Berberine, Syringic acid, Gallocatechin, Curcumin, Loureirin-A, Loureirin-B, Lupeol, Paeoniflorin, and Puerarin emerge from these studies as promising agents for diabetic wound healing through the inhibition of the NF-κB pathway. Extensive research on various phytoconstituents has revealed how they modulate signalling pathways, including NF-κB, studies that demonstrate the potential for development of therapeutic phytoconstituents to assist healing of chronic diabetic wounds.

Current Insights into the Role of BRAF Inhibitors in Treatment of Melanoma.

Melanomas represent only 4% of all skin cancers, but their mortality rate is more than 50 % of any other skin cancer. Alteration in genetic and environmental factors are the risk factors for melanoma development. The RAS/RAF/MEK/ERK or Mitogen-activated protein kinase (MAPK) pathway is activated in melanoma. BRAF activation is necessary to govern differentiation, proliferation, and survival. Mutations in BRAF were found in 80-90% of all melanomas. Over 90% of BRAF mutations occur at codon 600, and over 90% of them are BRAFV600E other common mutations are BRAFV600K, BRAFV600R, BRAF V600'E2', and BRAF V600D. Based on αC-helix and DFG motif (αC-helix-IN/DFG-IN), (αC-helix-IN/DFG-OUT), (αC-helix-OUT/DFG-IN) and (αC-helix-OUT/ DFG-OUT) are four structural types of inhibitors for targeting BRAF. Sorafenib, Vemurafenib, Dabrafenib, and Encorafenib are FDAapproved for the treatment of BRAF. Understanding melanoma pathogenesis, RAS/RAF/MEK/ERK or MAPK pathway, and BRAF conformations, mutations, the problems with FDA approved BRAF inhibitors will be important for new drug discovery, modification of existing BRAF barriers to improve target specific action, and prevent increasing response levels while minimizing toxicity.

Bacteriophages Concept and Applications: A Review on Phage Therapy.

The nature of phages was a matter of dispute, which was resolved in 1940, and it was continued to develop their activity and application in the Soviet Union and Eastern Europe. Bacteriophages were first employed in 1919 to treat bacterial illnesses caused by Citrobacter, Enterobacter, and Pseudomonas. Bacteriophages range in complexity from simple spherical viruses with genome sizes of less than 5 kbp to complicated viruses with genome sizes surpassing 280 kbp. They have two significant parts, head and tail, and are made up of numerous copies of more than 40 distinct proteins. Bacteriophages have been demonstrated to bind with receptors in the walls of both gram-positive and gram-negative bacteria, ranging from peptide sequences to polysaccharide moieties. Depending on the type of phage and the physiological state of the bacterium, the life cycle may diverge into the lytic cycle or lysogenic cycle. Lytic-lysogenic switch depends on a variety of inducing factors. Bacteriophage therapy can be administered via several routes, but parenteral routes are the most effective. Auto-dosing, single-dose potential, lack of cross-resistance with antibiotics, etc., are several advantages of phage therapy over antibiotic treatment. Bacteriophages are attracting much attention because of their potential advantages and wide applications as antibacterial agents, diagnostic technologies, phage-based products, and biocontrol agents. They also have several applications in the food industry, agriculture/crop, farm animal and bee protection, environmental, and biosensor development.

Electrochemical oxidation and sensing of para benzoquinone using a novel SPE based disposable sensor.

Para-benzoquinone (PBQ) is an emerging micro-contaminant owing to its chronic toxicity to plants and animals as well as its potential to induce cytotoxicity in primary rat hepatocytes and kidney cell injury. Hence, it is of utmost importance to monitor this contaminant in industrial wastewater and groundwater. In this article, we devised a unique disposable sensor that is based on a screen-printed electrode using MnO2@Co-Ni MOFs/fMWCNTs nanocomposite and is able to detect PBQ. The as-produced nanocomposite was prepared via ultrasonic assisted reflux condition and thoroughly examined by several physicochemical characterisation methods such as SEM, EDX, TEM, Raman, AFM, UV-visible, and FT-IR. Moreover, electrochemical methods like CV, DPV, EIS, and chronoamperometry were used for detecting PBQ on MnO2@Co-Ni MOFs/fMWCNTs/SPCE. Sensor performance has been investigated thoroughly and optimized to enhance the analytical potential of the fabricated sensor. DPV analysis was done on MnO2@Co-Ni MOFs/fMWCNTs that exhibit high selectivity, low peak potential, a broader linear detection range (0.005 mM-30 mM), and a LOD of 0.0027 ± 0.0005 mM. The designed electrode has shown remarkable reproducibility and excellent repeatability, with relative standard deviations of 0.12%, and 0.17%, respectively. Additionally, MnO2@Co-Ni MOFs/fMWCNTs/SPCE have been used to analyse PBQ in industrial wastewater samples, and the results have shown a significant level of recovery between 96.91 and 105.67%. Moreover, the PBQ sensor displays high applicability and was verified via the use of HPLC techniques. This disposable sensor is quick, easy, and cost-effective, so it can be useful in the future for analysing other phenolic contaminants present in environmental samples.

Design, Synthesis and Molecular Docking Studies Pyrazoline Derivatives as PI3K Inhibitors.

AIM: Design, synthesis and molecular docking studies of quinoline/naphthalene containing pyrazoline derivatives as PI3K inhibitors. BACKGROUND: Phosphatidylinositol 3-kinases (PI3Ks) belong to the family of enzymes, which are associated with various cellular functions such as cell growth, proliferation, differentiation etc. Overexpression or any changes in these functions may result in various abnormalities, which in turn cause cancer. OBJECTIVES: To perform synthesis and molecular docking studies of quinoline/naphthalene containing pyrazoline derivatives as PI3K inhibitors. METHODS: 2-Chloroquinoline-3-carbaldehyde was synthesized by a reaction of acetanilide and POCl3. The latter was reacted with substituted acetophenones to synthesize chalcones, which were reacted with substituted phenyl hydrazines to yield pyrazoline derivatives (Series I). Similarly, p-chloro benzaldehyde was reacted with 2-acetonapthone to yield chalcone with substituted phenyl hydrazines to yield pyrazoline derivatives (Series II). RESULTS: The synthetic compounds were subjected to molecular modelling experiments using Schrodinger 2016 software and evaluated in silico for their PI3K binding affinities. All the compounds had better docking scores than AMG-319 (-4.36) and comparable docking scores with PI-103 (-6.83). CONCLUSION: Compounds 5 and 3 had the best docking scores (-7.85 and -7.17, respectively). The synthesized compounds have better docking scores than the reference drug AMG-319. As a result, they might be used as lead molecules in investigating PI3K inhibitors.

A highly efficient NiCo2O4 decorated g-C3N4 nanocomposite for screen-printed carbon electrode based electrochemical sensing and adsorptive removal of fast green dye.

Herein, we demonstrate the preparation and application of NiCo2O4 decorated over a g-C3N4-based novel nanocomposite (NiCo2O4@g-C3N4). The prepared material was well characterized through several physicochemical techniques, including FT-IR, XRD, SEM, and TEM. The electrochemical characterizations via electrochemical impedance spectroscopy show the low electron transfer resistance of NiCo2O4@g-C3N4 owing to the successful incorporation of NiCo2O4 nanoparticles on the sheets of g-C3N4. NiCo2O4@g-C3N4 nanocomposite was employed in the fabrication of a screen-printed carbon electrode-based innovative electrochemical sensing platform and the adsorptive removal of a food dye, i.e., fast green FCF dye (FGD). The electrochemical oxidation of FGD at the developed NiCo2O4@g-C3N4 nanocomposite modified screen-printed carbon electrode (NiCo2O4@g-C3N4/SPCE) was observed at an oxidation potential of 0.65 V. A wide dual calibration range for electrochemical determination of FGD was successfully established at the prepared sensing platform, showing an excellent LOD of 0.13 µM and sensitivity of 0.6912 µA.µM-1.cm-2 through differential pulse voltammetry. Further, adsorbent dose, pH, contact time, and temperature were optimized to study the adsorption phenomena. The adsorption thermodynamics, isotherm, and kinetics were also investigated for efficient removal of FGD at NiCo2O4@g-C3N4-based adsorbents. The adsorption phenomenon of FGD on NiCo2O4@g-C3N4 was best fitted (R2 = 0.99) with the Langmuir and Henry model, and the corresponding value of Langmuir adsorption efficiency (qm) was 3.72 mg/g for the removal of FGD. The reaction kinetics for adsorption phenomenon were observed to be pseudo-second order. The sensitive analysis of FGD in a real sample was also studied.

Answer to comments on: 'Voltammetric analysis of epinephrine using glassy carbon electrode modified with nanocomposite prepared from Co-Nd bimetallic nanoparticles, alumina nanoparticles and functionalized multiwalled carbon nanotubes' by Ida Tiwari et al., (Doi: 10.1007/s11356-022-23660-y).

This is an answer to the letter by the editor that was sent in response to our previously published article entitled "Voltammetric analysis of epinephrine using glassy carbon electrode modified with nanocomposite prepared from Co-Nd bimetallic nanoparticles, alumina nanoparticles and functionalized multiwalled carbon nanotubes." We are grateful to the writers for showing an interest in our manuscript and for providing such helpful feedback. We emphasise that our research was just a preliminary investigation to detect epinephrine in different biological samples, however, in literature a link between epinephrine and acute respiratory distress syndrome (ARDS) is already reported. Hence, we are agreeing to the authors that epinephrine is suggested as a cause for ARDS following anaphylaxis. It is recommended that more research be carried out to evaluate the possibility of epinephrine as a cause for ARDS and to validate the therapeutic relevance of the findings. Additionally, the purpose of our research was electrochemical sensing of epinephrine alternative to the conventional means like HPLC, fluorimetry, etc. for epinephrine detection. We have found that benefits which the electrochemical sensors have, are their simplicity, cost-effectiveness, ease of use owing to their small size, mass manufacture, and straightforward operation, as well as their extreme sensitivity and selectivity, hence the electrochemical sensing methods are more beneficial than conventional techniques for epinephrine analysis.