Discovery of Potential RAGE inhibitors using Receptor-Based Pharmacophore Modeling, High Throughput Virtual Screening and Docking Studies.

Receptor for Advanced Glycation End products (RAGE) is a transmembrane receptor that can bind to various endogenous and exogenous ligands and initiate the inflammatory downstream signaling pathways. So far RAGE has been involved in various disorders including cardiovascular and neurodegenerative diseases, cancer, and diabetes. Blocking the interactions between RAGE and its ligands is a therapeutic approach to treat these conditions. In this context, we effectively utilized the receptor-based-pharmacophore modeling to discover structurally diverse molecular compounds having potential to effectively bind with RAGE. Two pharmacophore models were developed on V-domain of RAGE using Phase application of Schrodinger suite. The developed pharmacophoric features were used for screening of 1.8 million drug-like molecules downloaded from ChEMBL database. The molecules were scrutinized according to their molecular weight as well as clogP values. Phase screening was performed to find out the molecules that matched the developed pharmacophoric features that were further selected to analyze their binding modes using high-throughput virtual screening, extra precision docking studies and MM-GBSA ΔG binding calculations. These analyses provided ten hit RAGE inhibitory molecules that can bind to two different shallow binding sites on the V-domain of RAGE. Among the obtained compounds two compounds ChEMBL501494 and ChEMBL4081874 were found with best binding free energies that proved their receptor-ligand complex stability within their respective binding cavity on RAGE. Therefore, these molecules could be utilized for further designing and optimizing the future class of potential RAGE inhibitors.

Recent advances in nanobiosensors for sustainable healthcare applications: A systematic literature review.

The need for novel healthcare treatments and drugs has increased due to the expanding human population, detection of newer diseases, and looming pandemics. The development of nanotechnology offers a platform for cutting-edge in vivo non-invasive monitoring and point-of-care-testing (POCT) for rehabilitative disease detection and management. The advancement and uses of nanobiosensors are currently becoming more common in a variety of scientific fields, such as environmental monitoring, food safety, biomedical, clinical, and sustainable healthcare sciences, since the advent of nanotechnology. The identification and detection of biological patterns connected to any type of disease (communicable or not) have been made possible in recent years by several sensing techniques utilizing nanotechnology concerning biosensors and nanobiosensors. In this work, 2218 articles are drawn and screened from six digital databases out of which 17 were shortlisted for this review by using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) technique. As a result, this study uses a systematic methodology to review some recently developed extremely sensitive nanobiosensors, along with their biomedical, point-of-care diagnostics (POCD), or healthcare applications and their capabilities, particularly for the prediction of some fatal diseases based on a few of the most recent publications. The potential of nanobiosensors for medicinal, therapeutic, or other sustainable healthcare applications, notably for ailments diagnostics, is also recognized as a way forward in the manifestation of future trends.

End fire linear antenna array synthesis using differential evolution inspired Adaptive Naked Mole Rat Algorithm.

Linear antenna arrays (LAAs) play a critical role in smart system communication applications such as the Internet of Things (IoT), mobile communication and beamforming. However, minimizing secondary lobes while maintaining a low beamwidth remains challenging. This study presents an enhanced synthesis methodology for LAAs using the Adaptive Naked Mole Rat Algorithm (ANMRA). ANMRA, inspired by mole-rat mating habits, improves exploration and exploitation capabilities for directive LAA applications. The performance of ANMRA is assessed using the CEC 2019 benchmark test functions, a widely adopted standard for statistical evaluation in optimization algorithms. The proposed methodology results are also benchmarked against state-of-the-art algorithms, including the Salp Swarm Algorithm (SSA), Cuckoo Search (CS), Artificial Hummingbird Algorithm (AHOA), Chimp Optimization Algorithm (ChOA), and Naked Mole Rat Algorithm (NMRA). The results demonstrate that ANMRA achieves superior performance among the benchmarked algorithms by successfully minimizing secondary lobes and obtaining a narrow beamwidth. The ANMRA controlled design achieves the lowest Side Lobe Level (SLL) of - 37.08 dB and the smallest beamwidth of 74.68°. The statistical assessment using the benchmark test functions further confirms the effectiveness of ANMRA. By optimizing antenna element magnitude and placement control, ANMRA enables precise primary lobe placement, grating lobe elimination, and high directivity in LAAs. This research contributes to advancing smart system communication technologies, particularly in the context of IoT and beamforming applications, by providing an enhanced synthesis methodology for LAAs that offers improved performance in terms of secondary lobe reduction and beamwidth optimization.

Improving the segmentation of digital images by using a modified Otsu's between-class variance.

Image segmentation is a critical stage in the analysis and pre-processing of images. It comprises dividing the pixels according to threshold values into several segments depending on their intensity levels. Selecting the best threshold values is the most challenging task in segmentation. Because of their simplicity, resilience, reduced convergence time, and accuracy, standard multi-level thresholding (MT) approaches are more effective than bi-level thresholding methods. With increasing thresholds, computer complexity grows exponentially. A considerable number of metaheuristics were used to optimize these problems. One of the best image segmentation methods is Otsu's between-class variance. It maximizes the between-class variance to determine image threshold values. In this manuscript, a new modified Otsu function is proposed that hybridizes the concept of Otsu's between class variance and Kapur's entropy. For Kapur's entropy, a threshold value of an image is selected by maximizing the entropy of the object and background pixels. The proposed modified Otsu technique combines the ability to find an optimal threshold that maximizes the overall entropy from Kapur's and the maximum variance value of the different classes from Otsu. The novelty of the proposal is the merging of two methodologies. Clearly, Otsu's variance could be improved since the entropy (Kapur) is a method used to verify the uncertainty of a set of information. This paper applies the proposed technique over a set of images with diverse histograms, which are taken from Berkeley Segmentation Data Set 500 (BSDS500). For the search capability of the segmentation methodology, the Arithmetic Optimization algorithm (AOA), the Hybrid Dragonfly algorithm, and Firefly Algorithm (HDAFA) are employed. The proposed approach is compared with the existing state-of-art objective function of Otsu and Kapur. Qualitative experimental outcomes demonstrate that modified Otsu is highly efficient in terms of performance metrics such as PSNR, mean, threshold values, number of iterations taken to converge, and image segmentation quality.

Utilization of primary and secondary biochemical compounds in cotton as diagnostic markers for measuring resistance to cotton leaf curl virus.

Introduction: Cotton (Gossypium hirsutum L.) is one of the most important staple fibrous crops cultivated in India and globally. However, its production and quality are greatly hampered by cotton leaf curl disease (CLCuD) caused by cotton leaf curl virus (CLCuV). Therefore, the aim of the present study was to investigate the biochemical mechanisms associated with CLCuD resistance in contrasting cotton genotypes. Methods: Four commercial cotton varieties with susceptible (HS 6 and RCH-134 BG-II) and resistant (HS 1236 and Bunty) responses were used to analyze the role of primary (sugar, protein, and chlorophyll) and secondary (gossypol, phenol, and tannin) biochemical compounds produced by the plants against infection by CLCuV. The resistant cultivars with increased activity of protein, phenol, and tannin exhibited biochemical barriers against CLCuV infection, imparting resistance in cotton cultivars. Results: Reducing sugar in the healthy plants of the susceptible Bt cultivar RCH 134 BG-II exhibited the highest value of 1.67 mg/g at 90 days. In contrast, the lowest value of 0.07 mg g-1 was observed at 60 DAS in the highly diseased plants of the susceptible hybrid HS 6. Higher phenol content (0.70 mg g-1) was observed at 90 DAS in resistant cultivars, whereas highly susceptible plants exhibited the least phenol (0.25 mg g-1) at 90 DAS. The lowest protein activity was observed at 120 DAS in susceptible cultivars HS 6 (9.4 mg g-1) followed by RCH 134 BG-II (10.5 mg g-1). However, other biochemical compounds, including chlorophyll, sugar, and gossypol, did not show a significant role in resistance against CLCuV. The disease progression analysis in susceptible cultivars revealed non-significant differences between the two susceptible varieties. Discussion: Nevertheless, these compounds are virtually associated with the basic physiological and metabolic mechanisms of cotton plants. Among the primary biochemical compounds, only protein activity was proposed as the first line of defense in cotton against CLCuV. The secondary level of defense line in resistance showed the activity of secondary biochemical compounds phenol and tannins, which displayed a significant increase in their levels while imparting resistance against CLCuV in cotton.

Therapeutic Potential of Targeting the HMGB1/RAGE Axis in Inflammatory Diseases.

High mobility group box 1 (HMGB1) is a nuclear protein that can interact with a receptor for advanced glycation end-products (RAGE; a multi-ligand immunoglobulin receptor) and mediates the inflammatory pathways that lead to various pathological conditions, such as cancer, diabetes, neurodegenerative disorders, and cardiovascular diseases. Blocking the HMGB1/RAGE axis could be an effective therapeutic approach to treat these inflammatory conditions, which has been successfully employed by various research groups recently. In this article, we critically review the structural insights and functional mechanism of HMGB1 and RAGE to mediate inflammatory processes. More importantly, current perspectives of recent therapeutic approaches utilized to inhibit the communication between HMGB1 and RAGE using small molecules are also summarized along with their clinical progression to treat various inflammatory disorders. Encouraging results are reported by investigators focusing on HMGB1/RAGE signaling leading to the identification of compounds that could be useful in further clinical studies. We highlight the current gaps in our knowledge and future directions for the therapeutic potential of targeting key molecules in HMGB1/RAGE signaling in the pathophysiology of inflammatory diseases.

Targeting the Crosstalk of Immune Response and Vascular Smooth Muscle Cells Phenotype Switch for Arteriovenous Fistula Maturation.

Plaque formation, thrombosis, and embolism are the underlying causes of acute cardiovascular events such as myocardial infarction and stroke while early thrombosis and stenosis are common pathologies for the maturation failure of arteriovenous fistula (AVF). Chronic inflammation is a common underlying pathogenesis mediated by innate and adaptive immune response involving infiltration of immune cells and secretion of pro- and anti-inflammatory cytokines. Impaired immune cell infiltration and change in vascular smooth muscle cell (VSMC) phenotype play a crucial role in the underlying pathophysiology. However, the change in the phenotype of VSMCs in a microenvironment of immune cell infiltration and increased secretion of cytokines have not been investigated. Since change in VSMC phenotype regulates vessel remodeling after intimal injury, in this study, we investigated the effect of macrophages and pro-inflammatory cytokines, IL-6, IL-1ß, and TNF-α, on the change in VSMC phenotype under in vitro conditions. We also investigated the expression of the markers of VSMC phenotypes in arteries with atherosclerotic plaques and VSMCs isolated from control arteries. We found that the inhibition of cytokine downstream signaling may mitigate the effect of cytokines on the change in VSMCs phenotype. The results of this study support that regulating or targeting immune cell infiltration and function might be a therapeutic strategy to mitigate the effects of chronic inflammation to attenuate plaque formation, early thrombosis, and stenosis, and thus enhance AVF maturation.

Dihydrofolate reductase inhibitors: patent landscape and phases of clinical development (2001-2021).

INTRODUCTION: Dihydrofolate reductase (DHFR) plays an important role in the biosynthesis of amino acid and folic acid. It participates by reducing dihydrofolate to tetrahydrofolate, in the presence of nicotinamide dinucleotide phosphate cofactor, and has been verified by various clinical studies to use DHFR as a target for the treatment of cancer and various bacterial infections. AREA COVERED: In this review, we have disclosed patents of synthetics and natural DHFR inhibitors with diaminopyrimidine and quinazoline nucleus from 2001. Additionally, this review highlights the clinical progression of numerous DHFR inhibitors received from the last five years. EXPERT OPINION: From 2001 to 2021, numerous active chemical scaffolds have been introduced and are exposed as lead candidates that have entered clinical trials as potent DHFR inhibitors. Moreover, researchers have paid considerable attention to the development of a new class of DHFR inhibitors with higher selectivity and potency. This development includes synthesis of synthetic as well as natural compounds that are potent DHFR inhibitors. On the basis of literature review, we can anticipate that there are a huge number of novel active molecules available for the future that could possess superior abilities to target this enzyme with a profound pharmacological profile.

Recent advancements in the discovery of cereblon-based protease-targeted chimeras with potential for therapeutic intervention.

Protease-targeted chimeras (PROTACs) have been employed as a novel therapeutic approach, utilizing the ubiquitin-proteasome system for targeted protein degradation. PROTACs are heterobifunctional molecules consisting of an E3 ligase ligand and a small-molecule inhibitor for recruiting a protein of interest. After binding, PROTAC molecules recruit E3 ligase for ubiquitination of the protein of interest, which is followed by its proteasome-mediated degradation. PROTAC molecules have several advantages over traditional small-molecule inhibitors. A number of PROTAC molecules based on small-molecule inhibitors have been developed against various diseases, among which cereblon-based PROTAC molecules have received the greatest interest due to their promising clinical use. This article highlights the current trends in the discovery of cereblon-based PROTAC molecules along with their medicinal chemistry, clinical progression and future outlook in cancers, cardiovascular diseases and neurodegenerative disorders.

TLR-4 Inhibition Attenuates Inflammation, Thrombosis, and Stenosis in Arteriovenous Fistula in Yucatan Miniswine.

Arteriovenous fistula (AVF) is the preferred vascular access in hemodialysis patients; however, it is afflicted with a high failure rate. Chronic inflammation, excessive neointimal hyperplasia (NIH), vessel stenosis, early thrombosis, and failure of outward remodeling are the major causes of AVF maturation failure. Inflammatory mediator toll-like receptor (TLR)-4 plays a critical role in NIH, arterial thrombosis, and stenosis. We investigated the effect of TLR-4 inhibition on early thrombosis. Yucatan miniswine were used to create AVF involving femoral artery and femoral vein and treated with TLR-4 inhibitor TAK-242 with ethanol as the vehicle. The vessels were assessed after 12 weeks using histomorphometry, immunostaining, ultrasound, angiography, and optical coherence tomography. Inhibition of TLR-4 attenuated inflammation and early thrombosis in 50% of animals, and blood flow was present through AVF in 25% of animals. Thus, targeting TLR-4 to attenuate inflammation and early thrombosis might be a therapeutic approach to keep AVF patent and maintain blood flow through the outflow vein.

Therapeutic potential of targeting the receptor for advanced glycation end products (RAGE) by small molecule inhibitors.

Receptor for advanced glycation end products (RAGE) is a 45 kDa transmembrane receptor of immunoglobulin family that can bind to various endogenous and exogenous ligands and initiate the inflammatory downstream signaling pathways. RAGE is involved in various disorders including cardiovascular and neurodegenerative diseases, cancer, and diabetes. This review summarizes the structural features of RAGE and its various isoforms along with their pathological effects. Mainly, the article emphasized on the translational significance of antagonizing the interactions of RAGE with its ligands using small molecules reported in the last 5 years and discusses future approaches that could be employed to block the interactions in the treatment of chronic inflammatory ailments. The RAGE inhibitors described in this article could prove as a powerful approach in the management of immune-inflammatory diseases. A critical review of the literature suggests that there is a dire need to dive deeper into the molecular mechanism of action to resolve critical issues that must be addressed to understand RAGE-targeting therapy and long-term blockade of RAGE in human diseases.

LPS and oxLDL-induced S100A12 and RAGE expression in carotid arteries of atherosclerotic Yucatan microswine.

BACKGROUND: S100A12, also known as Calgranulin C, is a ligand for the receptor for advanced glycation end products (RAGE) and plays key roles in cardiovascular and other inflammatory diseases. Interactions between S100A12 and RAGE initiate downstream signaling activating extracellular signal-regulated kinases (ERK1/2), mitogen activated protein kinases (MAPK), and transcription factor NF-κB. This increases the expression of pro-inflammatory cytokines to induce the inflammatory response. S100A12, and RAGE play a critical role in the development and progression of atherosclerosis. There is a well-known relationship between the bacterial endotoxin lipopolysaccharide (LPS) and the lipid antigens oxidized low-density lipoprotein (oxLDL) in driving the immune response in atherosclerosis. METHODS AND RESULTS: Our study aimed to compare the potential of LPS and oxLDL in regulating the expression of S100A12 and RAGE in atherosclerosis. The expression of these proteins was assessed in the harvested carotid arteries from LPS- and oxLDL-treated atherosclerotic Yucatan microswine. Tissues were collected from five different treatment groups: (i) angioplasty alone, (ii) LPS alone, (iii) oxLDL alone, (iv) angioplasty with LPS, and (v) angioplasty with oxLDL. Immunohistochemical findings revealed that angioplasty with LPS induced higher expression of S100A12 and RAGE compared to other treatment groups. The results were further corroborated by testing their gene expression through qPCR in cultured vascular smooth muscle cells (VSMCs) isolated from control carotid arteries and LPS- and oxLDL-treated arteries. CONCLUSIONS: The results of this study suggest that LPS induces the expression of S100A12 and RAGE more than oxLDL in atherosclerotic artery and both S100A12 and RAGE could be therapeutic targets.

Recent advances in the development of active hybrid molecules in the treatment of cardiovascular diseases.

Multifactorial nature of the underlying pathophysiology of chronic disorders hinders in the effective treatment and management of many complex diseases. The conventional targeted therapies have limited applications due to highly complicated disease etiology. Cardiovascular diseases (CVDs) are the group of disorders of the heart and blood vessels. Currently, there is limited knowledge on the underlying cellular and molecular mechanisms of many of the CVDs due to their complex pathophysiology and co-morbidities. Their management with conventional medications results in failure due to adverse drug reactions and clinical specificity of solo-targeting drug therapy. Therefore, it is critical to introduce an alternative strategy to treat multi-factorial diseases. In the past few years, discovery and use of multi-targeted drug therapy with hybrid molecules have shown promising results with minimal side effects, and thus considered a most effective approach. In this review article, prominent hybrid molecules combining with different active moieties are reported to synergistically and simultaneously block different pathways involved in CVDs. Here, we provide a critical evaluation and discussion on their pharmacology with mechanistic insights and the structure activity relationship. The timely information provided in this article reveals the recent trends of molecular hybridization to the scientific community interested in CVDs and help them in designing the next generation of multi-targeting drug therapeutics.

Design, synthesis, and biological evaluation of isatin-indole-3-carboxaldehyde hybrids as a new class of xanthine oxidase inhibitors.

A novel series of triazole-linked isatin-indole-3-carboxaldehyde hybrids based on the febuxostat skeleton and its binding site interactions were rationally designed and synthesized as potential xanthine oxidase inhibitors. Among the synthesized hybrids, A19 showed the most potent xanthine oxidase inhibition (IC50 = 0.37 µM) with the mixed-type inhibitory scenario. Structure-activity relationship studies revealed that methoxy (OCH3 ) substitution on position 5 of the isatin nucleus and a two-carbon distance between isatin and the triazole moiety is most tolerable for the inhibitory potential. Various binding interactions of A19 with the binding site of xanthine oxidase are also streamlined by molecular docking studies, which showcase the favorable binding pattern for xanthine oxidase inhibition by the hybrid. Furthermore, molecular dynamic studies were performed that suggest the stability of the enzyme-hybrid complex. Overall, the study suggests that hybrid A19 can act as an effective hit lead for further development of potent xanthine oxidase inhibitors.

Multi-exposure microscopic image fusion-based detail enhancement algorithm.

Traditional microscope imaging techniques are unable to retrieve the complete dynamic range of a diatom species with complex silica-based cell walls and multi-scale patterns. In order to extract details from the diatom, multi-exposure images are captured at variable exposure settings using microscopy techniques. A recent innovation shows that image fusion overcomes the limitations of standard digital cameras to capture details from high dynamic range scene or specimen photographed using microscopy imaging techniques. In this paper, we present a cell-region sensitive exposure fusion (CS-EF) approach to produce well-exposed fused images that can be presented directly on conventional display devices. The ambition is to preserve details in poorly and brightly illuminated regions of 3-D transparent diatom shells. The aforesaid objective is achieved by taking into account local information measures, which select well-exposed regions across input exposures. In addition, a modified histogram equalization is introduced to improve uniformity of input multi-exposure image prior to fusion. Quantitative and qualitative assessment of proposed fusion results reveal better performance than several state-of-the-art algorithms that substantiate the method's validity.

Donepezil-Inspired Multitargeting Indanone Derivatives as Effective Anti-Alzheimer's Agents.

In continuous efforts to develop anti-Alzheimer's agents, we rationally designed and synthesized a series of multitargeting molecules by incorporating the essential molecular features of the standard drug donepezil. Among the series, compound 4b showed multitargeting properties to act as an anti-Alzheimer's agent, which is better tolerable in vivo than donepezil. Acetylcholinesterase (AChE) inhibition data showed that compound 4b inhibits the enzyme with a half-maximal inhibitory concentration (IC50) value of 0.78 µM and also showed DNA protection, which was confirmed through the DNA nicking assay, suggesting the protective effect of 4b against oxidative DNA damage. Compound 4b also showed 53.04% inhibition against Aß1-42 aggregations, which was found comparable to that of the standard compound curcumin. Molecular dynamics simulations were performed to check the stability of compound 4b with the enzyme AChE, which showed that the enzyme-ligand complex is stable enough to block the hydrolysis of acetylcholine in the brain. Its higher LD50 cutoff value (50 mg/kg) in comparison to donepezil (LD50: 25 mg/kg) made it safer, suggesting that it can be used in further clinical experiments. To evaluate its anti-Alzheimer property, a mice model with melamine-induced cognitive dysfunction was used, and Morris water maze and Rotarod tests were performed. A significant improvement in memory was observed after the treatment with compound 4b and donepezil. The study postulated that the introduction of important structural features of donepezil (dimethoxyindanone moiety as ring-A) embarked with terminal aromatic ether (ring-B and ring-C) made 4b a multitargeting molecule that offers a way for developing alternative therapeutics in the future against Alzheimer's disease (AD).

Discovery of potent inhibitors for Mpro enzyme of SARS-COV2 by multi-stage in-silico screening of Alkannin/shikonin.

Novel coronavirus disease, a serious challenge for the healthcare system, has diverted all the researchers toward the exploration of potential targets, compounds or vaccines for the management of this disease. Mpro enzyme was found to be crucial for replication of this virus which makes this enzyme an attractive drug target for SARS-CoV-2. Diverse pharmacological profile of Alkannin/shikonin (A/S) derivatives build up curiosity to study their antiviral profile. Therefore, current study utilises various computational tools to screen and evaluate all the discovered A/S derivatives to inhibit the Mpro enzyme for its anti-viral activity. Results revealed that the A/S has a very good tendency to inhibit the catalytic activity of the enzyme. Moreover, (5 R,6R)-5,8-dihydroxy-6-methoxy-3,4,5,6-tetrahydro-2H-benzo[a]anthracene-1, 7, 12-trione, an A/S derivative was found to possess drug-likeliness properties and a good ADME profile. Moreover, its complex with Mpro enzyme was found stable for 50 ns which makes it a very promising ligand to treat COVID-19.

Design, Synthesis, biological investigations and molecular interactions of triazole linked tacrine glycoconjugates as Acetylcholinesterase inhibitors with reduced hepatotoxicity.

Tacrine is a known Acetylcholinesterase (AChE) inhibitors having hepatotoxicity as main liability associated with it. The present study aims to reduce its hepatotoxicity by synthesizing tacrine linked triazole glycoconjugates via Huisgen's [3 + 2] cycloaddition of anomeric azides and terminal acetylenes derived from tacrine. A series of triazole based glycoconjugates containing both acetylated (A-1 to A-7) and free sugar hydroxyl groups (A-8 to A-14) at the amino position of tacrine were synthesized in good yield taking aid from molecular docking studies and evaluated for their in vitro AChE inhibition activity as well as hepatotoxicity. All the hybrids were found to be non-toxic on HePG2 cell line at 200 µM (100 % cell viability) as compared to tacrine (35 % cell viability) after 24 h of incubation period. Enzyme kinetic studies carried out for one of the potent hybrids in the series A-1 (IC50 0.4 µM) revealed its mixed inhibition approach. Thus, compound A-1 can be used as principle template to further explore the mechanism of action of different targets involved in Alzheimer's disease (AD) which stands as an adequate chemical probe to be launched in an AD drug discovery program.

Discerning the promising binding sites of S100/calgranulins and their therapeutic potential in atherosclerosis.

INTRODUCTION: Atherosclerosis is a chronic inflammatory disease in which the members of S100 family proteins (calgranulins) bind with their receptors, particularly receptor for advanced glycation end products (RAGE) and toll-like receptor-4 (TLR-4) and play a key role in the pathogenesis and progression of disease. Thus, these proteins could be considered as potential biomarkers and therapeutic targets in the treatment of atherosclerotic inflammation. AREAS COVERED: This review summarizes the pathology of S100A8, S100A9, and S100A12 in the development of atherosclerosis and reveals key structural features of these proteins which are potentially critical in their pathological effects. This article focuses on the translational significance of antagonizing these proteins by using small molecules in patent literature, clinical and preclinical studies and also discusses future approaches that could be employed to block these proteins in the treatment of atherosclerosis. EXPERT OPINION: Based on the critical role of S100/calgranulins in the regulation of atherosclerosis, these proteins are potential targets to develop better therapeutic options in the treatment of inflammatory diseases. However, further research is still needed to clarify their exact molecular mechanism by analyzing their detailed structural features that can expedite future research to develop novel therapeutics against these proteins to treat atherosclerotic inflammation.

Nonsubsampled contourlet transform based tone-mapping operator to optimize the dynamic range of diatom shells.

The diatoms have intricate silica-based cell walls with multi-scale patterns. High dynamic range (HDR) imaging is widely used to examine the three-dimensional structure of diatoms for recovering the wide range of contrast and brightness. In order to construct a HDR image of a diatom, multiple images of the specimen are taken at different exposure settings with bright or dark field microscopy. In the proposed method, multi-scale decomposition based on nonsubsampled contourlet transform is adopted to separate the structured and detailed information of the HDR image. And then, by processing all layers independently, the tone-mapped image is reconstructed to retain details present in the dark and light regions. Quantitative and qualitative analysis is performed in order to assess the performance of the proposed and seven existing tone-mapping operators. In analysis, the study indicates that the proposed method enhances the diatom frustules to extract more details.