Search

The green approach of synthesizing nanoparticles is an efficient, cost-effective, environmentally friendly, and rapid technique in which plant sources act as capping/stabilizing and reducing agents. The current study aimed to investigate the anticancer potential of biosynthesized Cu4O3NPs against the human ovarian teratocarcinoma cell line (PA-1). Scanning electron microscopy (SEM), transmission electron microscopy (TEM), and selected area electron diffraction (SAED) were used to predict the size and morphology of the biosynthesized nanoparticles. The SEM image revealed a 200 nm size of Cu4O3NPs; however, TEM data showed the spherical shape of the Cu4O3NPs in the range of ≤ 100 nm. A range of biological evaluations, such as cytotoxicity assay, morphological alteration, induction of apoptosis by three different staining techniques (AO/EB dual staining, DAPI, and PI staining), ROS production, and alteration in mitochondrial membrane potential were performed. We observed a dose-dependent cytotoxicity of Cu4O3NPs in the PA-1 cell line with an IC50dose of 9.5 µg/ml. Furthermore, Cu4O3NP treatment induced apoptosis, which was confirmed by all three adopted staining techniques while inducing ROS production and modulating mitochondrial membrane potential. Our findings highlight the anticancer potential of Cu4O3NPs against the studied cell line, which needs to be further explored because of its cost-effectiveness and eco-friendly nature.

AbstractRecently, multi-targeted drugs have attracted much attention in cancer therapy where several therapeutic proteins are targeted by a single agent. Using the published scientific literature, we selected sixteen well-known anticancer targets and seven potential phytobioactive chemicals to find a multitargeted compound by screening through molecular docking. The feasible protein–ligand interaction was further predicted by protein–ligand interaction analysis and molecular dynamic simulation. The phytochemical yohimbine exhibited the lowest docking score in the range of −8.3 to −10.0 kcal/mol over other ligands with all the studied protein targets. Molecular interaction data also revealed the feasible binding of yohimbine with all targets. Moreover, the molecular simulation data also confirmed the stability of protein-ligand complexes with three most scored targets viz. ERK2, PARP1 and PIK3α. Based on our results, yohimbine seems to be the most potent compound out of those selected compounds and can be considered as effective lead molecule against the studied target proteins.Communicated by Ramaswamy H. Sarma

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes the coronavirus disease 2019 (COVID-19), which first appeared in December 2019. Angiotensin I converting enzyme 2 (ACE2) receptor, present on the host cells, interacts with the receptor binding domain (RBD) of spike (S) protein of SARS-CoV-2 and facilitates the viral entry into host cells.Methods: Non-synonymous single nucleotide polymorphisms (nsSNPs) in the ACE2gene may have an impact on the protein's stability and its function. The deleterious or harmful nsSNPs of the ACE2gene that can change the strength as well as the pattern of interaction with the RBD of S protein were selected for this study.Results: The ACE2:RBD interactions were analyzed by protein-protein docking study. The missense mutations A242V, R708W, G405E, D292N, Y633C, F308L, and G405E in ACE2receptor were found to interact with RBD of Omicron subvariants with stronger binding affinity. Among the other selected nsSNPs of human ACE2(hACE2), R768W, Y654S, F588S, R710C, R710C, A191P, and R710C were found to have lower binding affinity for RBD of Omicron subvariants.Conclusion: The findings of this study suggest that the nsSNPs present in the human ACE2gene alter the structure and function of the protein and, consequently, the susceptibility to Omicron subvariants.

This study synthesized gold nanoparticles (AuNPs) using a facile microwave-assisted chemical route and evaluated them as potential anticancer candidates against breast and colon cancer cell lines. Numerous spectral characterization tools were used to study the optical properties, structure, and morphology of the prepared AuNPs. UV-Vis spectroscopy showed a characteristic peak at 517 nm, which confirms the formation of AuNPs. The crystalline structure of NPs was studied by X-ray diffraction, and the NPs’ shape and size were calculated with Field emission transmission electron microscopy. The synthesized AuNPs were found to be uniform in size in the range of 2–6 nm. A variety of biological tests, including MTT, scratch, real time polymerase chain reaction (RT-PCR), and comet assays were adopted to assess the anticancer potential of these AuNPs in the studied cancer cell models. The findings suggested a cell-dependent cytotoxicity of AuNPs. Different cell viability of 40.3 and 66.4% were obtained for MCF-7 and HCT-116, respectively, at 5 µg/mL of AuNPs. The scratch assay showed AuNPs impede cell migration in a concentration-dependent manner in the MCF-7 cell line. On the other hand, real-time polymerase chain reaction (RT-PCR) of apoptotic (p53, Bax, and caspase-3) and anti-apoptotic (BCl-2) genes revealed upregulation and downregulation of these genes, respectively, probably leading to its cytotoxicity. At 5 µg/mL concentration of AuNPs, reactive oxygen species (ROS) production was found to be increased by 26.4 and 42.7%, respectively, in MCF-7 and HCT-116 cells. Similarly, comet assay demonstrated AuNPs induced DNA damage in the studied cancer cell lines. These findings suggest that the observed anticancer efficacy of AuNPs was driven by ROS generation. The synthesized AuNPs appeared to be a promising therapeutic against cancer cells. However, our in vitrodata need to be confirmed and validated in ex vivoand in vivomodels so that this NP can be further exploited for human use.

The cost-effective and environmental friendly biosynthesis of metal nanoparticles is becoming increasingly important in biomedical science. This study biosynthesized zinc oxide nanoparticles (ZnO NPs) from pumpkin seed extract and assessed its anticancer activity by using different molecular biology experiments in human breast cancer (MDA-MB-231) cell lines. The well-known analytical techniques, such as UV-visible spectrophotometry, energy-dispersive X-ray spectroscopy, field emission scanning electron microscopy, and transmission electron microscopy (TEM), were used to confirm the synthesis and characterize the morphological and structural features of biogenic ZnO NPs. The formation of spherical nanoparticles with an average size of 50–60 nm was recorded using scanning electron microscopy and TEM. We observed the dose-dependent increase in cytotoxicity of ZnO NPs in the MDA-MB-231 cell line with a 50% inhibitory concentration of 10 µg/mL. Moreover, the ZnO NPs also showed significant cell morphology changes, apoptosis induction, and reactive oxygen species production at the highest tested concentration. The cellular adhesion and migration assay indicated cell death and inhibition in the migration of breast cancer cells in response to ZnO NPs’ treatment. These results clearly demonstrated the significant anticancer potential of ZnO NPs against the studied breast cancer cell line. However, an extension of this study is recommended in different cancer models and, based on the results, in vivovalidation should be done.

Innate lymphoid cells (ILCs), strategically positioned throughout the body, undergo population declines over time. A solution to counteract this problem is timely mobilization of multipotential progenitors from the bone marrow. It remains unknown what triggers the mobilization of bone marrow ILC progenitors (ILCPs). We report that ILCPs are regulated by the circadian clock to emigrate and generate mature ILCs in the periphery. We found that circadian-clock-defective ILCPs fail to normally emigrate and generate ILCs. We identified circadian-clock-controlled endocrine and cytokine cues that, respectively, regulate the retention and emigration of ILCPs at distinct times of each day. Activation of the stress-hormone-sensing glucocorticoid receptor upregulates CXCR4 on ILCPs for their retention in the bone marrow, while the interleukin-18 (IL-18) and RORα signals upregulate S1PR1 on ILCPs for their mobilization to the periphery. Our findings establish important roles of circadian signals for the homeostatic efflux of bone marrow ILCPs.

In continuation of our previous studies, we developed polymeric epigallocatechin 3-gallate (EGCG)-loaded nanoparticles (NPs) coupled with folic acid (FA), able to dually bind the human folate receptor alpha (FOLR1), and prostate-specific membrane antigen (PSMA+) in prostate cancer (PCa) model. After a preliminary computational molecular recognition of NP′ ligand binding on the FOLR1 active site, we synthesized the biocompatible block-copolymer PLGA–PEG–FA to prepare EGCG-targeted NPs (EGCG-T-NPs). The obtained NPs were characterized by various analytical techniques, and anticancer efficacy was determined by different sets of experiments in a 3D culture of PCa using PC3 and 22Rv1 cell lines. Results showed a significant reduction in spheroid size by EGCG-T-NPs, especially in PSMA+(22Rv1) cells. The targeted NPs significantly enhanced the antiproliferative activity of EGCG against PCa cell lines, especially toward the PSMA+cells, known to have higher FOLR1 expression. We did not observe any changes in the reactive oxygen species formation in both studied cell lines. However, significant changes in mitochondrial depolarization (15%) and polarization (18%) were recorded in response to EGCG-T-NP compared to control in 22Rv1. Similarly, EGCG-T-NP treatment also showed an increase in the number of dead apoptotic cells in 22Rv1 spheroids. Collectively, the obtained results support our hypothesis about the role of these targeted nanoprototypes in the increasing cellular uptake of EGCG payload into PCa cells, thus enhancing its antitumor efficacy.

AbstractAlzheimer’s disease (AD) is a growing global health concern that affects 10% of the population aged above 65 years. A growing body of evidence indicates that multi-targeted drugs might be useful therapeutic options owing to the heterogeneity of AD pathology. The current study exploited advanced computational biology tools to identify ligands that might display effective binding to two protein targets in the context of AD. The present study used in silicovirtual screening of small molecules library to identify effectiveness against two AD targets viz. acetyl cholinesterase (AChE) and glycogen synthase kinase-3β (GSK-3β). PyRX-Python prescription with AutodockVina was used to generate binding energy profiles. Further screening was accomplished using SwissADME and molecular interaction studies. The present study obtained 48 ligands (absolute binding energy >8 kcal/mol), by virtual screening of 100 ligands. Among those, 13 ligands (BRW, 6VK, 6Z5, SMH, X37, 55E, 65 A, IQ6, 6VL, 6VM, F1B, 6Z2 and GVP) were selected based on blood brain barrier (BBB) permeability, acceptable ADME properties as well as their molecular interaction profiles with the aforementioned AD-targets. The present study has predicted certain molecules that appear worthy to be tested for effectiveness against two AD targets, namely AChE and GSK-3β. However, the results warrant further wet laboratory validation, as computational studies are merely predictive in nature. This approach might be useful for future treatment of AD.Communicated by Ramaswamy H. Sarma

Background: With the burgeoning worldwide aging population, the incidence of Alzheimer’s disease (AD) and its associated disorders is continuously rising. To appraise other relevant drug targets that could lead to potent enzyme targeting, 13 previously predicted ligands (shown favorable binding with AChE (acetylcholinesterase) and GSK-3 (glycogen synthase kinase) were screened for targeting 3 different enzymes, namely butyrylcholinesterase (BChE), monoamine oxidase A (MAO-A), and monoamine oxidase B (MAO-B) to possibly meet the unmet medical need of better AD treatment. Materials and Methods: The study utilized in silico screening of 13 ligands against BChE, MAO-A and MAOB using PyRx-Python prescription 0.8. The visualization of the active interaction of studied compounds with targeted proteins was performed by Discovery Studio 2020 (BIOVIA). Results: The computational screening of studied ligands revealed the docking energies in the range of -2.4 to -11.3 kcal/mol for all the studied enzymes. Among the 13 ligands, 8 ligands (55E, 6Z2, 6Z5, BRW, F1B, GVP, IQ6, and X37) showed the binding energies of ≤ -8.0 kcal/mol towards BChE, MAO-A and MAO-B. The ligand 6Z5 was found to be the most potent inhibitor of BChE and MAO-B, with a binding energy of -9.7 and -10.4 kcal mol, respectively. Molecular dynamics simulation of BChE-6Z5 and MAO-B-6Z5 complex confirmed the formation of a stable complex. Conclusion: Our computational screening, molecular docking, and molecular dynamics simulation studies revealed that the above-mentioned enzymes targeted ligands might expedite the future design of potent anti-AD drugs generated on this chemical scaffold.

COVID-19 emerged by the end of 2019 in Wuhan, China. It spreaded and became a public health emergency all over the world by mid of April 2020. Flavonoids are specialized metabolites that have antimicrobial properties including anti-viral activity. Rutin, a medicinally important flavonoid belongs to one of the best natural antioxidant classes. It has antiprotozoal, antibacterial, and antiviral properties. Keeping the antimicrobial potential of rutin in mind, we studied its role in the inhibition of essential proteins of SARS-CoV-2 including main protease (Mpro), RNA-dependent RNA polymerase (RdRp), papain-like protease (PLpro), and spike (S)-protein through different in silicoapproaches.

AbstractMethylglyoxal (MG) is a potent glycating agent which reacts with proteins to form advanced glycation end products (AGEs). These chemically stable AGEs crosslink with proteins and could lead to amyloid formation that has the role in several diseases including Alzheimer’s and Parkinson’s. In this piece of work, glycation-induced conformational changes in HSA were observed with quenching of tryptophan fluorescence by 73.8% (41 nm red shift) and loss of hydrophobicity of HSA. CD spectroscopy result reaffirmed secondary structure changes in HSA. Moreover, MG-induced changes in HSA, proceeds to amyloid structure as characterized by an increase in thioflavin (ThT) fluorescence and transmission electron microscopy (TEM) images of HSA aggregates. Quercetin was found to inhibit both AGEs production and amyloid formation. Viability of MCF-7 cells was found to be increased with AGEs treatment, illustrating proliferation of cancer cells. Wound healing assay also revealed increased proliferation and migration of cells in the presence of AGEs. Additionally, molecular docking analyses were performed to demonstrate interactions involved in the stabilization of HSA-quercetin complex. The binding affinities of quercetin were found to be (Kd= 105M−1) much higher compared with MG (Kd= 102M−1). From this study, it is quite clear that quercetin reverses the effect of MG by sterically inhibiting the interaction between HSA and MG.Communicated by Ramaswamy H. Sarma

Background: The inhibition of cholinesterase enzymes is one of the promising strategies to manage several neurological disorders that include Alzheimer's disease (AD). Material and Methods: In the current article, we estimated the potential inhibition of acetyl cholinesterase (AChE) by phenserine using slightly modified Ellman assay. To find out the binding interactions of phenserine with the catalytic site of AChE, a molecular docking study was also performed. Results: Phenserine was found to inhibit Electrophorus electricus AChE in a dose-dependent manner with an IC50 value of 0.013 μM. The kinetic analyses indicate that phenserine inhibits AChE in a mixed type manner (competitive and uncompetitive) with Ki values of 0.39 μmole/l and 0.21 μmole/l, respectively. On the other hand, Km and Vmax values were found to be 0.17 μM and 0.39 μM, respectively. The molecular docking studies indicate efficient binding of phenserine through 6 hydrogen bonds, 4 pi-alkyl interactions, and 1 pi-pi interaction within the AChE catalytic pocket. Conclusion: Results of our computational and kinetics studies indicated a mixed type inhibition by phenserine at AChE catalytic site.

Background: Protein kinases are the enzymes involved in phosphorylation of different proteins which leads to functional changes in those proteins. They belong to serine-threonine kinases family and are classified into the AGC (Protein kinase A/ Protein kinase G/ Protein kinase C) families of protein and Rho-associated kinase protein (ROCK). The AGC family of kinases are involved in G-protein stimuli, muscle contraction, platelet biology and lipid signaling. On the other hand, ROCK regulates actin cytoskeleton which is involved in the development of stress fibres. Inflammation is the main signal in all ROCK-mediated disease. It triggers the cascade of a reaction involving various proinflammatory cytokine molecules. Methods: Two ROCK isoforms are found in mammals and invertebrates. The first isoforms are present mainly in the kidney, lung, spleen, liver, and testis. The second one is mainly distributed in the brain and heart. Results: ROCK proteins are ubiquitously present in all tissues and are involved in many ailments that include hypertension, stroke, atherosclerosis, pulmonary hypertension, vasospasm, ischemia-reperfusion injury and heart failure. Several ROCK inhibitors have shown positive results in the treatment of various disease including cardiovascular diseases. Conclusion: ROCK inhibitors, fasudil and Y27632, have been reported for significant efficiency in dropping vascular smooth muscle cell hyper-contraction, vascular inflammatory cell recruitment, cardiac remodelling and endothelial dysfunction which highlight ROCK role in cardiovascular diseases.

Complication in the hepatic system is a major concern for human being. To control and keep the hepatic system healthy, a number of measures, including drug treatments are considered. Diterpenes are essential oils having promising antioxidant and cytotoxic properties along with their genotoxic and mutagenic effects. These agents are good targets for health promotion, especially in the light of their potential organo-protectivity. We searched in the databases, PUBMED and SCIENCE DIRECT from June 2011 to June 2016 for publishing evidence on diterpenes and their effects on hepatic system. After sorting the data, activity-wise findings are discussed in this current article. The results suggest that diterpenes have hepatoprotectivity property via antioxidant and anti-inflammatory, antimicrobial, anticancer/antitumor, hypolipidemic, anti-apoptosis, autophagic, antimetastasize, anti-proliferating, anti-fibrosis as well as receptor and serum biomarkers mediated pathways. On the other hand, hepatoxic effects of diterpenes are also accounted with cytotoxicity, apoptotic cell death and downregulation of cytochrome P450 systems. A number of important diterpenes have been reported in the literatures that act on the hepatic system. Some of them exert toxic effects on the liver, especially in rodent model. Hence, more extensive researches are recommended that will highlight their mechanism of action on the liver.

The transport of more than 90% of the drugs viz. anticoagulants, analgesics, and general anesthetics in the blood takes place by albumin. Hence, albumin is the prime protein needs to be investigated to find out the nature of drug binding. Serum albumin molecules are prone to glycation at elevated blood glucose levels as observed in diabetics. In this piece of work, glycation of bovine serum albumin (BSA) was carried out with glyceraldehyde and characterized by molecular docking and fluorometry techniques. Glycation of BSA showed 25% loss of free amino groups and decreased protein fluorescence (60%) with blue shift of 6 nm. The present study was also designed to evaluate the binding of colchicine (an anti-inflammatory drug) to native and glycated BSA and its ability to displace 8-analino-1-nephthalene sulfonic acid (ANS), from the BSA–ANS complex. Binding of ANS to BSA showed strong binding (Ka = 4.4 μM) with native conformation in comparison to glycated state (Ka = 8.4 μM). On the other hand, colchicine was able to quench the fluorescence of native BSA better than glycated BSA and also showed weaker affinity (Ka = 23 μM) for glycated albumin compared with native state (Ka = 16 μM). Molecular docking study showed that both glyceraldehyde and colchicine bind to common residues located near Sudlow’s site I that explain the lower binding of colchicine in the glycated BSA. Based on our results, we believe that reduced drugs-binding affinity to glycated albumin may lead to drugs accumulation and precipitation in diabetic patients.

Background: The popular drink, coffee (Coffea arabica) is under the great attention of late because of its promising pharmacological potential. Caffeine (the major constituent of coffee) is known for its prominent psychoactive impact. This review aims at highlighting the therapeutic potentials of caffeine and other five coffee components viz. caffeic acid, chlorogenic acids, cafestol, ferulic acid and kahweol and their mechanisms of action. Methods: An up-to-date search was made with selected keywords in PubMed, Science Direct, Web of Science, Scopus, The American Chemical Society and miscellaneous databases (e.g., Google Scholar) for the published literature on the selected topic. Results: A number of pharmacological activities are attributed to these components that include anti-oxidant, antiinflammatory, immunomodulatory, anti-microbial, anti-cancer, cardioprotective and neuroprotective effects. In addition, osteogenesis (kahweol), anti-diabetic (caffeine, chlorogenic acid and ferulic acid) and hepatoprotective (chlorogenic acid) activities have also been reported by some of these components in the scientific literature. Caffeine has also been noted for adverse effect on the development of the brain at early stages and reproductive systems. Conclusion: A more advanced pre-clinical and clinical trials are recommended to investigate the safety profiles of these coffee components before their use as possible therapeutics.

Background & Objective: Cancer is one of the leading causes of death worldwide. In view of ever increasing number associated with cancer related death, there is an urgent need to find out a novel compound especially of natural origin (better efficacy, less or non-toxic and cost effective) that could serve against the treatment of all forms of cancer. Currently, available treatment options related to cancer have their certain limitations especially in the case of solid tumors. Method: In search of the natural anticancer compound, alkaloids, in general, have been exploited by the scientist working in this field of research. Among these alkaloids, azoles (secondary metabolite) have been significantly highlighted in literature because of their anticancer potential and better efficacy against various forms of cancer. Results: Their mechanism of action includes induction in the cleavage of poly-ADP ribose polymerase (PARP), induction of caspase 3 and caspase 9, modulation of nuclear factor kappa B, damage to DNA, cell cycle arrest at G1 and G2/M stage, apoptosis and c-Myb inhibition. In the current article, we have tried to cover various azoles especially from oxazoles, thiazoles and carbazoles class that have been reported for their anticancer potential. Conclusion: Based on our article, we believe that, soon, the scientific community will come up with certain azole which will work against cancer at large rather than a specific type of cancer.

Cells constantly adapt to external humoral cues like cytokines and hormones, but practically most cellular behavior is under locally guided control via cell–cell interactions. Galectins (Gals) are one of the most prominent members of the group of molecules involved in this intercellular signaling. They are the family of β-galactoside specific lectins and consist of 15 different types, each with a specific function. They play crucial role in the immune system, inflammation, wound healing and carcinogenesis. In recent times, the role of Gals in the development of cardiovascular disease (CVD) has gained attention. Gals have been reported to act ambiguously by both relieving ischemia and accelerating atherosclerosis. Atherosclerosis can ultimately lead to myocardial infarction or ischemic stroke, which are both associated with Gals. There is also a role for Gals in the development of myocarditis by their influence on inflammatory processes. Moreover, Gal acts as a biomarker for the severity of myocardial ischemia and heart failure (HF). This review summarizes the association between Gals and the development and pathogenesis of CVD like atherosclerosis, stroke, myocardial infarction, and HF. A comprehensive outline of the association between Gals and more general mechanisms such as angiogenesis, arteriogenesis and atherosclerosis has also been provided. Modulation of Gal signaling holds great promise for the treatment of CVD as evident from preclinical studies.

Despite recent advances in medical research, the incidence of diabetes and cardiovascular disease (CVD)-induced fatal events is increasing. The literature point towards several co-occurring pathways that could lead to terminal complications related with these diseases. Different pathophysiological alterations such as hyperglycaemia, hyperinsulinaemia, insulin resistance, obesity, endothelial dysfunction and oxidative stress lead to the initiation and progression of atherosclerotic plaques. In view of the continuous rise in fatal events and overlapping pathological conditions associated with CVD and diabetes, there is a critical need to develop a common treatments against these diseases. The present review highlights the possible use of common drugs that could target diabetes and associated CVD.

Alzheimer’s disease (AD) is an irreversible multifaceted neurodegenerative disorder that gradually degrades neuronal cells. Presently, it is the most common reason for the memory loss and dementia in older individuals. It is patho-physiologically described by extracellular amyloid beta (Aβ) deposition, intracellular neurofibrillary tangles (NFTs) retention, neuronal decline, and neurotransmitter system derangement. Various receptors such as nicotinic acetylcholine, N-methyl-D-aspartate, insulin, serotonin, adenosine, and histamine are actively involved in the physiological progression of AD. Till date memantine and only four other acetylcholinesterase inhibitors have been approved for the treatment of AD by US Food and Drug Administration (US-FDA). Hence, there is a critical need to explore and develop novel and helpful management systems which could specifically target different receptors involved in AD progression. We believe that these receptors targeting will either impede the disease onset or slow down its pathogenesis. In the present review, we tried to uncover some receptors that could be blocked by novel inhibitors and ultimately used for the therapeutic management of AD.

Cerebrovascular disease (CD) and metabolic syndrome (MetS) are two devastating health dilemma that continues to be a potential contributor to disability and mortality in human population all across the world. Scientific data clearly shows several mechanistic similarities between these two co-existing and interlinked conditions. The linkage exacerbates ongoing patho-physiological condition towards more lethal events. In view of the presence of modifiable risk factors in both CD and MetS, their management holds potential therapeutic value. Hence, developing common treatment strategies for these diseases could involve common molecular agents. In this communication, we have summarized some of the common pathological conditions viz. abdominal obesity, insulin resistance, dyslipidemia, hypertension, and endothelial dysfunction that further deteriorate existing homeostasis in CD and MetS. Based on our article, it is advocated that substantial improvements in novel multi-targeted drug discovery could provide the effective treatment methods in order to avoid the fatal complications related with CD and MetS.

The non-enzymatic reaction (glycation) of reducing sugars with proteins has received increased interest in dietary and therapeutic research lately. In the present work, the impact of glycation on structural alterations of camel serum albumin (CSA) by different glucose metabolites was studied. Glycation of CSA was evaluated by specific fluorescence of advanced glycation end-products (AGEs) and determination of available amino groups. Further, conformational changes in CSA during glycation were also studied using 8-analino 1-nephthlene sulfonic acid (ANS) binding assay, circular dichroism (CD) and thermal analysis. Intrinsic fluorescence measurement of CSA showed a 22 nm red shift after methylglyoxal treatment, suggesting glycation induced denaturation of CSA. Rayleigh scattering analysis showed glycation induced turbidity and aggregation in CSA. Furthermore, ANS binding to native and glycated-CSA reflected perturbation in the environment of hydrophobic residues. However, CD spectra did not reveal any significant modifications in the secondary structure of the glycated-CSA. Thioflavin T (ThT) fluorescence of CSA increased after glycation, illustrated cross β-structure and amyloid formation. Transmission electron microscopy (TEM) analysis further reaffirms the formation of aggregate and amyloid. In summary, glucose metabolites induced conformational changes in CSA and produced aggregate and amyloid structures.

The two most common forms of dementia are Alzheimer’s disease (AD) followed by vascular dementia (VaD), together accounting for a whopping 60-80% of total dementia cases worldwide. Even though these diseases are recognized as ‘common’, they still remain underdiagnosed. Recent research suggests that AD and VaD are closely intertwined. The symptoms of AD and VaD can be similar and the two conditions can occur simultaneously. A large number of patients diagnosed with AD have also been reported with VaD-caused brain damage. Moreover, both the diseases have been reported to have similar risk factors. The overlap between these diseases is important because the lifestyle changes and medications prescribed to curb one of these diseases may also help curb the other. In the present review, we present an inclusive outline of parallelism between AD and VaD by exploring the potential commonalities at the mechanistic and therapeutic levels.

Cardio vascular disease (CVD) is the end result of the accumulation of atheromatous plaques within the walls of the coronary arteries and remains the leading cause of death worldwide. Vascular inflammation and associated ongoing inflammatory responses have been considered as the critical culprits in the pathogenesis of CVD. Moreover, the activation of inflammatory pathways is not confined to coronary lesions only but involves the activation of neutrophils, monocytes and lymphocytes in peripheral blood. In view of high mortality rate associated with this devastated disease, it is essential that CVD and related complications should be taken care off at its earliest. To achieve that goal, some inflammatory mediators could be potentially targeted. In the current article, we will highlight targeting some inflammatory mediators viz. IL-1, IL-6, TNF-α etc for CVD management. As far as our knowledge goes, we are for the first time reporting the targeting inflammatory mediators especially IL-1, IL-6 and TNF-α together in a single article. Based on our review, we believe that scientific community will come up with certain anti-inflammatory agents against atherosclerosis in near future and hopefully that will be used for the successful management of CVD patients.

Despite the significant advances in the medical research and treatment methods, the rate of mortality associated with cardiovascular disease (CVD) is continuously rising and it remains the leading cause of death worldwide. There are several treatment methods for CVD and associated complications that have been considered till now. The current treatment methods cannot produce rapid cure, but could prevent or reduce the progression of this devastating disease. In the current article, we have summarized the use of various pharmacological agents viz. HMG-CoA reductase inhibitors (statins), antihypertensive, thrombolytic and anticoagulation agents that are currently being used for the management of CVD which targets different biochemical or molecular events. Based on our article, more research in this field is advocated which will provide the rapid and effective treatment methods in order to avoid fatal complications associated with CVD.

Lectins are the (glyco)proteins that recognize and bind to specific sugar moieties without altering their structure. Galectins are mammalian lectins characterized by the presence of conserved 134 amino acids carbohydrate recognition domain and specificity for -galactosides. The involvement of lectins in diverse biological spectrum, especially some deadly human diseases like cancer, neurological disorders and cardiovascular disorders has proclaimed them as one of the important components of glycobiology, thereby seeking the methods of their detection and identification heavily desirable. In the present manuscript, we have provided a comprehensive outline of various methods of detection and identification of lectins employed till date, with their needs and usage varying according to the level of infrastructure of laboratories and around the world. In addition, a vision for some quick, highly sensitive and advanced methods for lectin detection and identification for diagnostic and therapeutic of various diseases is also provided.

Despite extensive research for over two decades, the medical science is yet to assign the exact aetiology and mode of progression of Alzheimer's disease (AD). The modern era of AD drug development began with the proposal of the cholinergic hypothesis of memory impairment. Since then, despite the proposal and phase trials of many therapeutic options, only few drugs have shown some efficacy and safety. The reasons behind this have been many including the ineffectiveness of tested drugs and inadequacy of clinical development methods. In this manuscript, we present an account of modern structural, functional and molecular imaging developed for AD therapy. A comprehensive review of all the current and future treatment options for AD, ranging from cholinergic drugs, NMDA receptor antagonist, immunotherapy, drugs reducing A production, and drugs targeting tau protein and mitochondrial dysfunction has also been provided. However, the failure of all the proposed treatment options to provide a complete cure of AD has been pushing for the need of new therapies. The recent advent of nano-drugs has been proposed to provide crucial breakthroughs in AD therapy. Hence, a detailed outline of the usage and applications of nano-drugs in AD therapy, and outstanding developments in nanodrug metabolism and disposition has been discussed.

Epilepsy is a non-communicable central nervous system disorder that affects over 60 million people worldwide. The developments in epilepsy treatment face major hurdles due to drug resistance and disease recurrence after reduction in medication. Nano-technological anti-epileptic drug (AED) delivery systems have recently garnered attention due to their ability to cross the blood brain barrier, improved selectivity and potential for sustained drug delivery to the brain. This review focuses on several nano-based AED delivery systems, including liposomes, nano-emulsions, polymeric nanoparticles, solid-lipid nanoparticles and magnetic nanoparticles. Their limitations and future prospects in terms of AED delivery to the brain are also highlighted. It is hoped that the present communication will be helpful in the identification of potential AED delivery systems based on their advantages and disadvantages.

Background:Because of the potential association between periodontal disease and inflammation, the purpose of the present study is to examine the level of Toll‐like receptor 4 (TLR‐4), interleukin‐18 (IL‐18), and uric acid as markers of the inflammatory host response in the plasma and saliva of healthy individuals and patients with periodontitis. In addition, routine biochemical parameters such as fasting glucose, insulin, total cholesterol, high‐density lipoprotein (HDL) cholesterol, low‐density lipoprotein (LDL) cholesterol, triglycerides, alanine transaminase (ALT), and aspartate transaminase (AST) were measured. The authors also wanted to check whether patients with chronic periodontitis (CP) exhibit different modulations in salivary and/or plasma concentrations of these parameters compared with clinically healthy individuals. Methods:Saliva and plasma samples were collected from 40 patients with CP and 20 healthy individuals. TLR‐4 and IL‐18 measurements were done using commercially available enzyme‐linked immunosorbent assay kits. Total, HDL, and LDL cholesterol; triglycerides; fasting glucose; AST; and ALT levels were analyzed on a biochemistry analysis system using specific kits. Non‐parametric tests were used for certain parameters in the statistical analyses because the data did not follow Gaussian distribution. Results:Significant differences were observed in plasma and salivary TLR‐4 and IL‐18 levels, along with clinical measurements such as plaque index and probing depth, in patients with CP (P<0.001). The plasma level of TLR‐4 was found to be increased from 0.99 to 3.28 ng/mL in patients with CP. Salivary TLR‐4 levels also showed a slightly higher increase in the diseased state (12.44 to 29.97 ng/mL). A significant increase of ≈46% was recorded in the plasma IL‐18 level. However, salivary IL‐18 levels rose up to >5‐fold in the patients with CP compared with healthy individuals. The level of plasma uric acid was found to be highly significantly increased compared with control individuals. HDL cholesterol and triglyceride also showed significant differences (P<0.02 and P<0.03, respectively). Plasma glucose, total cholesterol, LDL cholesterol, and insulin levels did not show any significant difference. There was only a slight increase in plasma AST and ALT levels between diseased and healthy states (22.55 versus 25.50 IU/L and 12.35 versus 15.95 IU/L, respectively). However, salivary AST and ALT levels showed a ≈6‐fold rise in the patients with CP compared with the healthy individuals. Cross‐correlation analysis in the periodontitis disease group showed a significant association of plasma AST, salivary AST, and salivary ALT with uric acid level. Conclusions:Based on this study, the authors believe that TLR‐4, IL‐18, and uric acid could have a role in the inflammatory pathology of periodontitis. These parameters are suggested to be useful in the prognosis and diagnosis of CP. However, the mechanistic association of these parameters with inflammatory pathology of patients with periodontitis needs to be further elucidated in a higher number of samples.

MicroRNAs (miRNAs) have emerged as key gene regulators controlling the expression of many target mRNAs. The nervous system harbors highest number of miRNAs expressed in a spatially and temporally controlled manner. Neural miRNAs have been accredited with diverse roles like regulation of neural differentiation, synaptogenesis, inflammation, memory and cognition. Their aberrant expression and/or function has been linked to various neurodegenerative, neuroinflammatory and stress related disorders. Recent evidence indicates that miRNAs are essential to the fine tuning of the immune responses. Besides controlling the maturation, proliferation and differentiation of myeloid and lymphoid lineages they participate directly by modulating the signaling pathways through the Toll-like receptors and thus the cytokine response. The miRNAs commuting between the nervous and immune systems and affecting the neuro-immune dialogue are emerging.

Background: Alzheimer's disease (AD) is an irreversible multifaceted neurodegenerative disorder that gradually degrades neuronal cells. It is the most frequent cause of memory loss and dementia in elderly individuals worldwide. The extracellular deposition of beta amyloid (Aβ), intracellular neurofibrillary tangles (NFTs) retention, neuronal decline and neurotransmitter system derangement are the patho-physiological marker of this devastated disease Objective: In view of limited treatment option and their success rate, there is an urgent need to explore the vast array of proteomes for the management of AD. These proteins could be therapeutically targeted to prevent the progression of this disease. In the present review, we tried to uncover several proteins that could be exploited in AD therapeutics. Conclusion: Based on our article, we conclude that proteome based AD treatment needs more refinements and approaches to achieve the desired success rate.