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Due to its potential impact on food safety and human health, commercial species that have been contaminated with microplastics (MPs) are drawing more attention on a global scale. This study investigated the possibility of MPs contamination in different marine fish species with substantial commercial value that was captured off the south coast of India, from Adyar and Ennore regions. Over the course of six months, from October 2019 to March 2020, 220 fish were examined. It was discovered that the gills and guts had accumulated more numbers of MPs (1115 MPs) of which 68% were fibres and fragments. The commercial fish samples contained an average of 3.2-7.6 MPs per fish. Greater MPs pollution is seen in the Ennore regions. The prevalence of MPs was observed in carnivorous and planktivorous fish collected from both the sites. Fish guts contained the most MPs, according to the data. Pelagic fish accounted for the least amount of MPs, followed by mid- and demersal fish. Four different types of polymers were also identified in the present study: polyethylene, polypropylene, polystyrene, and polyamide. These results clearly showed the degree of microplastic contamination in fish tissues from the south Indian coastal regions of Adyar and Ennore. These results we hope will create a baseline data for MPs contamination in commercial fish species. The presence of MPs in the fish could have detrimental effects both on the environment and human health and thus comprehensive steps are required to prevent plastic pollution of the environment in south India's coastal region.

Nanomaterials are being put to use extensively and new applications for nanotechnology are growing everyday. Nanomaterials beyond certain levels are an important class of environmental pollutant and thus are biologically toxic. Owing to their unique physicochemical properties, their behavior in the environment and inside biological systems are completely different when compared to their bulk counterparts or xenobiotics in general. Due to this, nanotoxicology has emerged out as a unique field of research involved in understanding the biological toxicity and environmental fate of released nanomaterials/nanoparticles. A variety of physicochemical properties such as dose/concentration, size, shape/morphology, aspect ratio, surface area, agglomeration/aggregation state, surface property, etc., influence nanomaterial behavior in the environment and toxicity in vivo. These properties can be utilized as a tool to devise strategies for reducing nanoparticle toxicity. In other words, the physicochemical properties of the various nanomaterials can be used for predicting their toxicity and for developing practices or protocols for the synthesis of specific types of nanomaterials with the aim of increasing their nanosafety.

Textile effluents contain high levels of pollutants of different categories like dyes, metal salts, acids, bases and microorganisms. Remediation of textile effluents is often challenging because of its composition, which also varies between dyeing units. In this study, we demonstrate the novel use of a waste-water bacterium, Escherichia fergusonii, in the effective remediation of textile effluents. The bacteria application efficiently caused a reduction of color (98.4%), total dissolved solids (75%), sulphates (87%), bicarbonates (83%), chlorides (64%), calcium (84%), and chemical oxygen demand (81%) of the textile effluents. The bacteria-treated effluents were further disinfected and detoxified by treating with rice husk activated charcoal. After the charcoal treatment, the chemical oxygen demand decreased further by 11.5% and biochemical oxygen demand decreased by 85%. The effluents remediated using the two-step process were subjected to toxicity assays using zebrafish (Danio rerio) model. The textile effluents treated using Escherichia fergusonii, followed by activated charcoal were found to be non-toxic and suitable for reuse for domestic applications. Thus, we present here, a simple, less energy-intensive, economic, two-step process as a complete solution for textile effluent treatment. The results of this investigation can be used to simplify the remediation process of textile effluents in common treatment plants as well as the individual dyeing units.

Aims To enhance the antimicrobial and antibiofilm activity of norfloxacin against the planktonic and biofilm mode of growth in ESKAPE pathogens using chemically modified norfloxacin salts. Methods and results Antimicrobial testing, synergy testing and time-kill curve analysis were performed to evaluate antibacterial effect of norfloxacin carboxylic acid salts against ESKAPE pathogens. In vivo efficacy to reduce bacterial bioburden was evaluated in zebrafish infection model. Crystal violet assay and live-dead staining were performed to discern antibiofilm effect. Membrane permeability, integrity and molecular docking studies were carried out to ascertain the mechanism of action. The carboxylic acid salts, relative to parent molecule norfloxacin, displayed two- to fourfold reduction in minimum inhibitory concentration against Staphylococcus aureus and Pseudomonas aeruginosa, in addition to displaying potent bacteriostatic effect against certain members of ESKAPE pathogens. In vivo treatments revealed that norfloxacin tartrate (SRIN2) reduced MRSA bioburden by greater than 1 log fold relative to parent molecule in the muscle tissue. In silico docking with gyrA of S. aureus showed increased affinity of SRIN2 towards DNA gyrase. The enhanced antibacterial effect of norfloxacin salts could be partially accounted by altered membrane permeability in S. aureus and perturbed membrane integrity in P. aeruginosa. Antibiofilm studies revealed that SRIN2 (norfloxacin tartrate) and SRIN3 (norfloxacin benzoate) exerted potent antibiofilm effect particularly against Gram-negative ESKAPE pathogens. The impaired colonization of both S. aureus and P. aeruginosa due to improved norfloxacin salts was further supported by live-dead imaging. Conclusion Norfloxacin carboxylic acid salts can act as potential alternatives in terms of drug resensitization and reuse. Significance and impact of the study Our study shows that carboxylic acid salts of norfloxacin could be effectively employed to treat both planktonic- and biofilm-based infections caused by select members of ESKAPE pathogens.

7-ketocholesterol, a toxic oxidative product of oxysterol is a causative agent of several diseases and disabilities concomitant to aging including cardiovascular diseases like atherosclerosis. Auto-oxidation of cholesterol esters present in low-density lipoprotein (LDL) deposits lead to the formation of oxidized LDL (Ox-LDL) along with its byproducts, namely 7KCh. It is predominantly found in atherosclerotic plaque and also found to be more atherogenic than cholesterol by being cytotoxic, interfering with cellular homeostasis. This makes it a serious threat by being the foremost cause of morbidity and mortality worldwide and is likely to become more serious during forth coming years. It involves in mediating inflammatory mechanisms characterized by the advancement of fibroatheroma plaques. The atherosclerotic lesion is composed of Ox-LDL along with fibrotic mass consisting of immune cells and molecules. Macrophages being the specialized phagocytic cells, contribute to removal of detrimental contents of the lesion along with accumulated lipids leading to alteration of its biology and functionality due to its plasticity. Here, we have explored the known as well as proposed mechanisms involved with 7KCh associated atherogenesis along with potential therapeutic strategies for targeting 7KCh as a diagnostic and target in medicine.

Cryptococcus neoformans, an encapsulated fungal pathogen is evolving as a major threat to immune-compromised patients and rarely to healthy individuals also. The cell wall bound capsular polysaccharide, melanin pigment and biofilm formation are major virulence factors that are known to contribute to cryptococcal meningitis. In the present study, a furanone derivative, (E)-5-benzylidenedihydrofuran-2(3H)-one (compound-6) was evaluated against biofilm of seven different strains of C. neoformans in melanized and non-melanized condition. In addition, the efficacy of compound-6 in activation of TLR-2, opsonophagocytosis, and modulation of cytokine expression during phagocytosis were studied. During the biofilm study, we found that moderate capsule size favored biofilm formation. Interestingly, the minimum biofilm eradication concentration (MBEC0.5) of melanized biofilm was found to be achieved at 1- to 1.7-fold higher MBEC0.5 of non-melanized cells. The maximum eradication of 77% and 69% of non-melanized and melanized biofilm were observed. The capsule size was reduced to half of its size with marked changes in morphology. Furthermore, expression of TLR2, iNOS and pro-inflammatory cytokines such as TNF-α, IL-12, and IFN-γ were also facilitated by compound-6. The correlation analysis showed a positive correlation between phagocytosis and the expression of TLR-2, iNOS, IL-6, IL-12. Collectively, the significant effect of compound-6, anti-melanization activity, antibiofilmand effective immunomodulant could be an interesting dual strategy drug agonist against cryptococcal meningitis.

Fluorescent carbon quantum dots (CQDs) synthesized using an amino acid-based phenolic chelating ligand, 2-(2-hydroxybenzylamino)propanoic acid, via a hydrothermal method showed selective turn-on fluorescence for Zn2+ and turn-off for Pb2+ in aqueous medium. High-resolution transmission electron microscopy analysis revealed uniformly dispersed spherical CQDs (3–5 nm). Fourier transform infrared and X-ray photoelectron spectroscopy studies confirmed carboxyl, hydroxy and amine-based surface functional groups. The CQDs exhibited good fluorescence intensity at 488 nm as well as excitation wavelength-dependent fluorescence. Interestingly, Zn2+ addition selectively blue shifted the fluorescence from 488 to 460 nm with a broad fluorescence, which led to white emission in the solution. In contrast, Pb2+ addition substantially quenched the fluorescence with a red shift in λmax. Thus, the CQDs showed selective sensing of Zn2+ and Pb2+ ions in aqueous media with completely distinguishable response. Concentration-dependent studies suggested that the CQDs can detect down to μM concentrations of Zn2+ and Pb2+ ions. Interference studies revealed good selectivity for Zn2+ and Pb2+ ions in the presence of other metal cations. Importantly, the fluorescence sensing of both Zn2+ and Pb2+ ions was performed in zebrafish eggs to demonstrate the biological application of the synthesized CQDs.

Nanoparticles are being widely used as antibacterial agents with metal nanoparticles emerging as the most efficient antibacterial agents. There have been many studies which have reported the mechanism of antibacterial activity of nanoparticles on bacteria. In this review we aim to emphasize on all the possible mechanisms which are involved in the antibacterial activity of nanoparticles and also to understand their mode of action and role as bacterial enzyme inhibitor by comparing their antibacterial mechanism to that of antibiotics with enzyme inhibition as a major mechanism. With the emergence of widespread antibiotic resistance, nanoparticles offer a better alternative to our conventional arsenal of antibiotics. Once the biological safety of these nanoparticles is addressed, these nanoparticles can be of great medical importance in our fight against bacterial infections.

Multi drug resistant (MDR) pathogens pose a serious threat to public health since they can easily render most potent drugs ineffective. Efflux pump inhibitors (EPI) can be used to counter the MDR phenotypes arising due to increased efflux. In the present study, a series of dithiazole thione derivatives were synthesized and checked for its antibacterial and efflux pump inhibitory (EPI) activity. Among 10 dithiazole thione derivatives, real-time efflux studies revealed that seven compounds were potent EPIs relative to CCCP. Zebrafish toxicity studies identified four non-toxic putative EPIs. Both DTT3 and DTT9 perturbed membrane potential and DTT6 was haemolytic. Among DTT6 and DTT10, the latter was less toxic as evidenced by histopathology studies. Since DTT10 was non-haemolytic, did not affect the membrane potential, and was least toxic, it was chosen further for in vivo study, wherein DTT10 potentiated effect of ciprofloxacin against clinical strain of MRSA and reduced bacterial burden in muscle and skin tissue of infected zebrafish by ~ 1.7 and 2.5 log fold respectively. Gene expression profiling of major efflux transport proteins by qPCR revealed that clinical isolate of MRSA, in the absence of antibiotic, upregulated NorA, NorB and MepA pump, whereas it downregulates NorC and MgrA relative to wild-type strain of Staphylococcus aureus. In vitro studies with NorA mutant strains and substrate profiling revealed that at higher concentrations DTT10 is likely to function as a competitive inhibitor of NorA efflux protein in S. aureus, whereas at lower concentrations it might inhibit ciprofloxacin efflux through NorB and MepA as implied by docking studies. A novel non-toxic, non-haemolytic dithiazole thione derivative (DTT10) was identified as a potent competitive inhibitor of NorA efflux pump in S. aureus using in silico, in vitro and in vivo studies. This study also underscores the importance of using zebrafish infection model to screen and evaluate putative EPI for mitigating MDR strains of S. aureus.

Abuse of antibiotics and drastic decline in the development of new antibiotics has been attributed to the rapid evolution of antibiotic resistant pathogens. The applications of antibiotics for agriculture practices, growth promotion of animal, poultry and aquaculture has raised concerns in recent years for their role in the development of antimicrobial resistance in clinically relevant pathogens. In this chapter we have discussed the non-medical uses of antibiotics and its impact on antimicrobial resistance in clinical settings. Extensive research such as evidences for transfer of resistant genes and plasmids to clinically relevant pathogens is required to correlate non-medical use of antibiotics and evocation of antimicrobial resistance mechanisms.

Curcumin, a hydrophobic polyphenol derived from Curcuma longa, possesses anticancer, hepatoprotective, wound healing, hypoglycemic and apoptotic properties. It is also known to play a predominantly protective role in inflammatory eye diseases. Extensive studies have shown that curcumin with its pleiotropic properties mediates its effect through inhibition of transcription factors like NF-κB, enzymes like cyclooxygenases (COX), lipoxygenases (LOX), cytokines (TNF, IL-1) and downregulation of anti-apoptotic genes. Curcumin, being an antioxidant, fights free radicals, thus preventing free radical accumulation like advanced glycation end products (AGEs) and eventually reducing glaucoma, macular degeneration disorder, retinal detachment, uveitis and diabetic retinopathy. Curcumin inhibition of IL-1β production, activation of p38 and NF-κB, and decreased JNK activation, lead to its possible role in the treatment of dry eye syndrome. Studies have also revealed that administration of curcumin enhanced retinal antioxidants such as glutathione, superoxide dismutase, and catalase, and reduced TNF-α, and VEGF levels which are considered to be hallmarks of diabetic-associated complications of the eye. On the other side, curcumin has been shown to successfully delay the progression and maturation of cataract mediated by a variety of factors. Curcumin treatment studies show significant inhibition of neuronal and vascular damage during ischemic or oxidative stress, allergic conjunctivitis and maculopathy. Thus, from these studies, it is obvious that curcumin is a pleiotropic “drug” and has great versatility as far as its pharmacological activities are concerned. This makes curcumin a potential drug for cytoprotective as well as therapeutic purposes against diseases of the eye.

Additional file 1. Additional tables and figures.

Introduction AMP-activated protein kinase (AMPK) is a drug target for treatment of metabolic and cardiovascular complications. Extracts of Gentianaceace plants exhibit anti-diabetic and anti-atherosclerotic effects, however, whether their phyto-constitutents activate AMPK remains to be determined. Methods Molecular docking of Gentiana lutea constituents was performed with crystal structure of human α2β1γ1 trimeric AMPK (PDB ID: 4CFE ). Binding of Amarogentin (AG) to α2 subunit was confirmed through isothermal titration calorimetry (ITC) and in vitro kinase assays were performed. L6 myotube, HUH7 and endothelial cell cultures were employed to validate in silico and in vitro observations. Lipid lowering and anti-atherosclerotic effects were confirmed in streptozotocin induced diabetic mice via biochemical measurements and through heamatoxylin and eosin, Masson's trichrome and Oil Red O staining. Results AG interacts with the α2 subunit of AMPK and activates the trimeric kinase with an EC50 value of 277 pM. In cell culture experiments, AG induced phosphorylation of AMPK as well as its downstream targets, acetyl-coA-carboxylase (ACC) and endothelial nitric oxide synthase (eNOS). Additionally, it enhanced glucose uptake in myotubes and blocked TNF-α induced endothelial inflammation. Oral supplementation of AG significantly attenuated diabetes-mediated neointimal thickening, and collagen and lipid deposition in the aorta. It also improved circulating levels of lipids and liver function in diabetic mice. Conclusion In conclusion, AG exerts beneficial vasculo-metabolic effects by activating AMPK. General significance Amarogentin, a naturally occurring secoiridoid glycoside, is a promising lead for design and synthesis of novel drugs for treatment and management of dyslipidemia and cardiovascular diseases.

The objective of this work is to use simulation results of a back end of line (BEOL) construction known to be susceptible to white bump failure to predict Chip package interaction (CPI) failure risk of other designs, prior to running a reliability qualification. This learning is applied to new 7nm chip and package configurations for a wide range of design points. Key attributes include bump pattern, core versus coreless substrate effects, use of a jig during the reflow process, different substrate prepeg materials, impact of additional TEOS dielectric layers in the BEOL stack, and different die thicknesses. Simulations were carried out using the structural analysis module – Ansys MechanicalTM. Thermal boundary conditions were applied to mimic the chip reflow process. The simulation methodology predicted the lowest CPI risk for a 7nm qualification. An optimized package with a lower CTE substrate, additional TEOS layers and a thicker die was found to be the best case scenario with respect to white bump risk.

In this paper, we demonstrate photosensitive polyimide (PSPI) profile optimization to effectively reduce stress concentrations and enable PSPI as protection package-induced stress. Through detailed package simulation, we demonstrate ~45% reduction in stress as the sidewall angle (SWA) of PSPI is increased from 45 to 80 degrees in Cu pillar package types. Through modulation of coating and develop multi-step baking temperature and time, as well as dose energy and post litho surface treatments, we demonstrate a method for reliably obtaining PSPI sidewall angle >75 degree. Additionally, we experimentally validate the simulation findings that PSPI sidewall angle impacts chip package interaction (CPI). Finally, we conclude this paper with PSPI material and tool qualification requirements for future technology node based on current challenges.

Invasive fungal infections caused by opportunistic fungal pathogens have been emerging as a global problem of great concern as they are associated with increased morbidity and mortality. Despite this, there are very limited drugs of choice to treat fungal infections. The continuous usage of these drugs is associated with resistance development and thus this is another area of concern. Fungal enzymes represent one of the most important and potential targets for drug development, as they are essential for their growth and establishment in the host. In this review, we have discussed the well established and currently available enzyme inhibitors as therapeutic choices to treat fungal infections as well as those enzyme inhibitors that have been identified as suitable drug candidates to manage fungal infections. Thus, the study of fungal biosynthetic enzymes and their inhibitors could potentially show a promising way of drug development for emerging and re-emerging fungal infections of humans.

Platinum nanoparticles (PtNPs) with potent antibacterial activity were synthesized using pectin and sodium borohydride as capping and reducing agents, respectively. For the first time, the in vivo antibacterial activity of PtNPs was demonstrated using adult zebrafish as the animal model. As a proof of concept, zebrafish infected with a model pathogen, Escherichia coli and a fish-specific pathogen, Aeromonas hydrophila, were subjected to treatment with PtNPs. A bacteria colony count assay revealed that the PtNPs exhibit dose-dependent inhibition of bacterial proliferation and rescued zebrafish completely from bacteria infection. The mechanism of antibacterial action includes the loss of membrane integrity and generation of reactive oxygen species. Toxicology studies reveal that the antibacterial concentration of PtNPs used in this study is non-toxic to zebrafish. Being non-toxic to zebrafish, these PtNPs might open up new avenues in antimicrobial therapy for future biomedical applications.

In the present study, cobalt oxide (Co3O4) magnetic nanoparticles with block and sphere morphologies were synthesized using various surfactants, and the toxicity of the particles was analyzed by monitoring biomarkers of nanoparticle toxicity in zebrafish. The use of tartarate as a surfactant produced highly crystalline blocks of Co3O4 nanoparticles with pores on the sides, whereas citrate lead to the formation of nanoparticles with a spherical morphology. Co3O4 structure, crystallinity, size and morphology were studied using X-ray diffractogram and field emission scanning electron microscopy. Following an increase in nanoparticle concentration from 1 to 200 ppm, there was a corresponding increase in nitric oxide (NO) generation, induced by both types of nanoparticles [Co3O4-NP-B (block), r=0.953; Co3O4-NP-S (sphere), r=1.140]. Comparative analyses indicated that both types of nanoparticle produced significant stimulation at ≥5 ppm (P

In the present study, we have synthesized silver nanoparticles by a simple and eco-friendly method using unripe fruits of Solanum trilobatum. The aqueous silver ions when exposed to unripe fruits extract were reduced and stabilized over long time resulting in biosynthesis of surface functionalized silver nanoparticles. The bio-reduced silver nanoparticles were characterized by UV-visible spectroscopy, Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy-dispersive spectroscopy (EDX) and X-ray diffraction (XRD). These biologically synthesized silver nanoparticles were tested for its antibacterial activity against few human pathogenic bacteria including Gram-positive (Streptococcus mutans, Enterococcus faecalis) and Gram-negative (Escherichia coli, Klebsiella pneumoniae) bacteria. In addition, we also demonstrated anticancer activity of these nanoparticles in vitro against human breast cancer cell line (MCF 7) using MTT, nuclear morphology assay, Western blot and RT-PCR expression. These results taken together show the potential applications of biosynthesized silver nanoparticles using S. trilobatum fruits.

Bacterial resistance is a major clinical problem, which is compounded by both a lack of new antibiotics and emergence of multi- and extremely-drug resistant microbes. In this context, non-toxic nanoparticles could play an important role in conferring protection against bacterial infections and in this study we have made an attempt to show the usefulness of jacalin capped platinum nanoparticles in protecting zebrafish against multiple infections with Aeromonas hydrophila. Our results also indicate that use of nanoparticles promotes adaptive immune response against the pathogen, so much so that zebrafish is able to survive repetitive infection even after twenty one days of being treated with jacalin-capped platinum nanoparticles. This is significant given that platinum salt is not antibacterial and jacalin is non-immunogenic. Our study for the first time reveals a novel mechanism of action of nanoparticles, which could form an alternate antibacterial strategy with minimal bacterial resistance.

The emergence and spread of multi-drug resistant (MDR) especially carbapenem-resistant Klebsiella pneumoniae is a major emerging threat to public health, leading to excess in mortality rate as high as 50–86%. MDR K. pneumoniae manifests all broad mechanisms of drug resistance, hence development of new drugs to treat MDR K. pneumoniae infection has become a more relevant question in the scientific community. In the present study a potential Streptomyces sp. ASK2 was isolated from rhizosphere soil of medicinal plant. The multistep HPLC purification identified the active principle exhibiting antagonistic activity against MDR K. pneumoniae. The purified compound was found to be an aromatic compound with aliphatic side chain molecule having a molecular weight of 444.43 Da. FT-IR showed the presence of OH and C=O as functional groups. The bioactive compound was further evaluated for drug induced toxicity and efficacy in adult zebrafish infection model. As this is the first study on K. pneumoniae – zebrafish model, the infectious doses to manifest sub-clinical and clinical infection were optimized. Furthermore, the virulence of K. pneumoniae in planktonic and biofilm state was studied in zebrafish. The MTT assay of ex vivo culture of zebrafish liver reveals non-toxic nature of the proposed ASK2 compound at an effective dose. Moreover, significant increase in survival rate of infected zebrafish suggests that ASK2 compound from a new strain of Streptomyces sp. was potent in mitigating MDR K. pneumoniae infection.

This study investigated the potential of vitamin K1 against streptozotocin-induced diabetic cataract in Wistar rats. A single, intraperitoneal injection of streptozotocin (STZ) (35 mg/kg) resulted in hyperglycemia, accumulation of sorbitol and formation of advanced glycation end product (AGE) in eye lens. Hyperglycemia in lens also resulted in superoxide anion and hydroxyl radical generation and less reduced glutathione suggesting oxidative stress in lens. Hyperglycemia also resulted in increase in lens Ca2+ and significant inhibition of lens Ca2+ ATPase activity. These changes were associated with cataract formation in diabetic animals. By contrast treatment of diabetic rats with vitamin K1 (5 mg/kg, sc, twice a week) resulted in animals with partially elevated blood glucose and with transparent lenses having normal levels of sorbitol, AGE, Ca2+ ATPase, Ca2+, and oxidative stress. Vitamin K 1 may function to protect against cataract formation in the STZ induced diabetic rat by affecting the homeostasis of blood glucose and minimizing subsequent oxidative and osmotic stress. Thus, these results show that Vitamin K1 inhibits diabetic-cataract by modulating lens Ca2+ homeostasis and its hypoglycemic effect through its direct action on the pancreas.

Ras genes are pre-eminent genes that are frequently linked with cancer biology. The functional loss of ras protein caused by various point mutations within the gene, is established as a prognostic factor for the genesis of a constitutively active Ras-MAPK pathway leading to cancer. Ras signaling circuit follows a complex pathway, which connects many signaling molecules and cells. Several strategies have come up for targeting mutant ras proteins for cancer therapy, however, the clinical benefits remain insignificant. Targeting the Ras-MAPK pathway is extremely complicated due its intricate networks involving several upstream and downstream regulators. Blocking oncogenic Ras is still in latent stage and requires alternative approaches to screen the genes involved in Ras transformation. Understanding the mechanism of Ras induced tumorigenesis in diverse cancers and signaling networks will open a path for drug development and other therapeutic approaches.

A new lectin was purified to electrophoretic homogeneity from pronase treated human serum by a single-step of affinity chromatography on concanavalin A-Sepharose 4B. The isolated lectin agglutinated five types of vertebrate RBC, with highest titer against hen RBC. This activity was independent of divalent cations, insensitive to EDTA and specific to mannosamine, glucosamine as well as galactosamine. Purified lectin gave a single symmetrical peak in its native form with a molecular mass estimate of 6kDa in FPLC analysis and 6.5kDa by MALDI-TOF MS. SDS-PAGE analysis of the lectin revealed that it is a homo-oligomer of a 3kDa subunit protein. Isolated lectin did possess both, hemagglutinating and phenoloxidase activities, but did not exhibit any antibacterial or antifungal activities. In addition, this lectin could oxidize all nine different phenolic substrates tested, with hydroquinone proving to be the best among them. Phenoloxidase inhibitors namely, phenylthiourea and tropolone inhibited this oxidation activity.

Cadmium (Cd), classified as human carcinogen, is an extremely toxic heavy metal pollutant, and there is an increasing environmental concern for cadmium exposure through anthropogenic sources including cigarette smoke. Though Cd based nanoparticles such as cadmium oxide (CdO) are being widely used in a variety of clinical and industrial applications, the toxicity of CdO nanoparticles has not been well characterized. Herein we report the toxicity of CdO nanoparticles employing zebrafish as a model. Two different CdO nanoparticles were prepared, calcination of Cd(OH)2 without any organic molecule (CdO-1) and calcination of Cd-citrate coordination polymer (CdO-2), to evaluate and compare the toxicity of these two different CdO nanoparticles. Results show that zebrafish exposed to CdO-2 nanoparticles expressed reduced toxicity as judged by lower oxidative stress levels, rescue of liver carboxylesterases and reduction in metallothionein activity compared to CdO-1 nanoparticles. Histopathological observations also support our contention that CdO-1 nanoparticles showed higher toxicity relative to CdO-2 nanoparticles. The organic unit of Cd-citrate coordination polymer might have converted into carbon during calcination that might have covered the surface of CdO nanoparticles. This carbon surface coverage can control the release of Cd2+ ions in CdO-2 compared to non-covered CdO-1 nanoparticles and hence mitigate the toxicity in the case of CdO-2. This was supported by atomic absorption spectrophotometer analyses of Cd2+ ions release from CdO-1 and CdO-2 nanoparticles. Thus the present study clearly demonstrates the toxicity of CdO nanoparticles in an aquatic animal and also indicates that the toxicity could be substantially reduced by carbon coverage. This could have important implications in terms of anthropogenic release and environmental pollution caused by Cd and human exposure to Cd2+ from sources such as cigarette smoke.

Invasive fungal infections caused by opportunistic fungal pathogens have been emerging as a global problem of great concern as they are associated with increased morbidity and mortality. Despite this, there are very limited drugs of choice to treat fungal infections. The continuous usage of these drugs is associated with resistance development and thus this is another area of concern. Fungal enzymes represent one of the most important and potential targets for drug development, as they are essential for their growth and establishment in the host. In this review, we have discussed the well established and currently available enzyme inhibitors as therapeutic choices to treat fungal infections as well as those enzyme inhibitors that have been identified as suitable drug candidates to manage fungal infections. Thus, the study of fungal biosynthetic enzymes and their inhibitors could potentially show a promising way of drug development for emerging and re-emerging fungal infections of humans.

Cryptococcal meningitis caused by Cryptococcus neoformans, is a common opportunistic neural infection in immunocompromised individuals. Cryptococcus meningitis is associated with fungal burden with larger capsule size in cerebrospinal fluid (CSF). To understand the role of CSF constituents in capsule enlargement, we have evaluated the effect of artificial CSF on capsule induction in comparison with various other capsule inducing media. Two different strains of C. neoformans, an environmental and a clinical isolates were used in the present study. While comparing the various capsule inducing media for the two different strains of C. neoformans, it was observed that the capsule growth was significantly increased when grown in artificial CSF at pH 5.5, temperature 34°C for ATCC C. neoformans and 37°C for Clinical C. neoformans and with an incubation period of 72 h. In addition, artificial CSF supports biofilm formation in C. neoformans. While investigating the individual components of artificial CSF, we found that Mg(2+) ions influence the capsule growth in both environmental and clinical strains of C. neoformans. To confirm our results we studied the expression of four major CAP genes namely, CAP10, CAP59, CAP60, and CAP64 in various capsule inducing media and in different concentrations of Mg(2+) and Ca(2+). Our results on gene expression suggest that, Mg(2+) does have an effect on CAP gene expression, which are important for capsule biosynthesis and virulence. Our findings on the role of Mg(2+) ion as a signal for capsule induction will promote a way to elucidate the control mechanisms for capsule biosynthesis in C. neoformans.

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Objective To examine the relative importance of tumor necrosis factor receptor I (TNFRI) signaling in the hematopoietic tissue compartment in the progression of collagen-induced arthritis (CIA), a model of rheumatoid arthritis (RA). Methods DBA/1 mice were administered a lethal radiation dose and were then rescued with bone marrow derived from either DBA/1 or TNFRI−/− mice. CIA was then induced, and disease progression was characterized. Results Surprisingly, mice with CIA that received TNFRI−/− donor marrow developed increased disease severity as compared with control mice with CIA. This could not be attributed to an increased primary response to collagen or to the contribution of a non-DBA genetic background. In mice that received TNFRI−/− bone marrow, histologic markers of advanced disease were evident shortly after initiation of the immune response to collagen and long before clinical evidence of disease. Serum TNFα was undetectable, whereas serum interleukin-12 p40 levels were increased, at the end point of the study in mice that received TNFRI−/− bone marrow. Conclusion These data raise the intriguing possibility of the existence of an antiinflammatory, TNFRI-mediated circuit in the hematopoietic compartment. This circuit bears a resemblance to the switch in TNFα function that has been observed during the resolution of bacterial infections. These data suggest that TNFRI-mediated signals in the radioresistant tissues contribute to disease progression, whereas TNFRI-mediated signals in the radiosensitive tissues can contribute to protection from disease. We thus put forward the hypothesis that the degree of response to TNFα blockade in RA is dependent in part on the relative genetic strengths of these 2 pathways.

The most predominant opportunistic fungal pathogens Candida sp, Aspergillus and Cryptococcus sp are emerging as a global problem of great concern as it is associated with increased morbidity and mortality. Although there are different classes of approved antifungal agents like polyenes, pyrimidines, azoles, and echinocandins, the morbidity and mortality rate due to systemic infection remains high, due to its toxicity, narrow spectrum of activity and tolerability. The continuous usages of these drugs are associated with resistance development and thus this is another area of emerging global problem. In addition, biofilm formation by fungal pathogens are proven to be an important virulence factor and are resistant to host defense mechanism and antifungal agents. Combination therapy has shown to be a promising choice to overcome the emergence of drug resistance, minimizing the toxic effects by reducing the drug dosage, and to increase the spectrum of killing. In this chapter, we have reviewed the last 5 years’ developments made in combinational antifungal therapy with special emphasize on biofilm related infections and have presented a reappraisal of the current practices associated with immunotherapy to treat fungal infections and future challenges.

Diabetes is a systemic disease mainly characterized by chronic hyperglycemia and with extensive and long-lasting spiteful complications in central nervous systems (CNS). Astrocytes play an important role in the defense mechanism of CNS, with great ability of withstanding accumulation of toxic substances. Apart from functional disorders, hyperglycemia leads to slow progressive structural abnormalities in the CNS through oxidative stress pathways. However, the molecular mechanism by which neurons die under oxidative stress induced by high glucose (HG) remains largely unclear. Here, we report that HG-induced inflammation and neurodegeneration in brain tissues, brain astrocytes (C6), and pheochromocytoma (PC-12) cells are cultured in HG conditions. Our results show that the increases in phosphorylation of Akt and ERK1/2MAPK are associated with increased accumulations of reactive oxygen species (ROS) in neuronal cells, which simultaneously enhanced phosphorylations of tuberous sclerosis complex-2 (TSC-2) and mammalian target of rapamycin (mTOR) in the diabetic brain and in HG-exposed neuronal cells. Pharmacologic inhibition of Akt or ERK1/2 or siRNA-mediated gene silencing of TSC-2 suppressed the strong downregulation of TSC-2-mTOR activation. Findings of this study also demonstrate that HG resulted in phosphorylation of NF-κB, coinciding with the increased production of inflammatory mediators and activation of neurodegenerative markers. Pretreatment of cells with antioxidants, phosphoinositide3-kinase (PI3-K)/Akt, and ERK1/2 inhibitors significantly reduced HG-induced TSC-2 phosphorylation and restored NF-κB protein expression leading to decreased production of inflammatory mediators and neurodegenerative markers. These results illustrate that ROS functions as a key signaling component in the regulatory pathway induced by elevated glucose in neuronal cell activation leading to inflammation and neurodegeneration.

This review discusses the relationship between oxidative stress and cataract formation, molecular mechanism of curcumin action and potential benefits of treatment with the antioxidant curcumin. The first section deals with curcumin and endogenous antioxidants. The second section focuses on the action of curcumin on lipid peroxidation. Calcium homeostasis and curcumin will be discussed in the third section. The fourth section discusses the role of crystallin proteins that are responsible for maintaining lens transparency and the role of curcumin in regulating crystallin expression. The interaction of curcumin with transcription factors will be dealt in the fifth section. The final section will focus on the effect of curcumin on aldose reductase, which is associated with hyperglycemia and cataract. One of the strongest antioxidants is curcumin which has been shown to be very effective against cataract. This compound is better than other antioxidants in preventing cataract but its limited bioavailability can be addressed by employing nanotechnology.

Objectives Vitamin K is a potent regulator of vascular dynamics and prevents vascular calcification. Vitamin K is increasingly being recognized for its antioxidant and antiinflammatory properties. Recently we demonstrated that vitamin K1 (5 mg/kg) protects against streptozotocin-induced type 1 diabetes and diabetic cataract. The aim of this study was to determine whether the hypoglycemic action of vitamin K1 could inhibit early-onset diabetic nephropathy in a streptozotocin-induced rat kidney. Methods Male Wistar rats were administered with 35 mg/kg STZ and after 3 days were treated with vitamin K1 (5 mg/kg, twice a week) for 3 months. Blood glucose was monitored once a month. At the end of the study, animals were sacrificed and kidney was dissected out and analysed for free radicals, antioxidants, aldose reductase, membrane ATPases, histopathology evaluation and expression of pro- and anti-inflammatory cytokines. Urea, uric acid, creatinine, albumin and insulin levels were also estimated. Results Treatment of diabetic rats with vitamin K1 resulted in a decrease in blood glucose and prevented microalbuminuria. Vitamin K1 also reduced oxidative stress and protected renal physiology by modulating Ca 2+ and Na + /K + -ATPases. Vitamin K1 inhibited renal inflammation by reducing nuclear factor-κB and inducible nitric oxide synthase. Interleukin-10 levels were increased in renal tissues, suggesting the ability of vitamin K1 to trigger antiinflammatory state. The hypoglycemic action of vitamin K1 could have an indirect effect by inhibiting early-onset diabetic nephropathy triggered by high blood glucose. Conclusion Vitamin K1 could be an important nutrient based interventional strategy for early onset diabetic nephropathy.