Epigenetic Orchestration of Neurodegenerative Disorders: A Possible Target for Curcumin as a Therapeutic.

Epigenetic modulations play a major role in gene expression and thus are responsible for various physiological changes including age-associated neurological disorders. Neurodegenerative diseases such as Alzheimer's (AD), Parkinson's (PD), Huntington's disease (HD), although symptomatically different, may share common underlying mechanisms. Most neurodegenerative diseases are associated with increased oxidative stress, aggregation of certain proteins, mitochondrial dysfunction, inactivation/dysregulation of protein degradation machinery, DNA damage and cell excitotoxicity. Epigenetic modulations has been reported to play a significant role in onset and progression of neurodegenerative diseases by regulating these processes. Previous studies have highlighted the marked antioxidant and neuroprotective abilities of polyphenols such as curcumin, by increased activity of detoxification systems like superoxide dismutase (SOD), catalase or glutathione peroxidase. The role of curcumin as an epigenetic modulator in neurological disorders and neuroinflammation apart from other chronic diseases have also been reported by a few groups. Nonetheless, the evidences for the role of curcumin mediated epigenetic modulation in its neuroprotective ability are still limited. This review summarizes the current knowledge of the role of mitochondrial dysfunction, epigenetic modulations and mitoepigenetics in age-associated neurological disorders such as PD, AD, HD, Amyotrophic Lateral Sclerosis (ALS), and Multiple Sclerosis (MS), and describes the neuroprotective effects of curcumin in the treatment and/or prevention of these neurodegenerative diseases by regulation of the epigenetic machinery.

Designing and development of multi-epitope chimeric vaccine against Helicobacter pylori by exploring its entire immunogenic epitopes: an immunoinformatic approach.

BACKGROUND: Helicobacter pylori is a prominent causative agent of gastric ulceration, gastric adenocarcinoma and gastric lymphoma and have been categorised as a group 1 carcinogen by WHO. The treatment of H. pylori with proton pump inhibitors and antibiotics is effective but also leads to increased antibiotic resistance, patient dissatisfaction, and chances of reinfection. Therefore, an effective vaccine remains the most suitable prophylactic option for mass administration against this infection. RESULTS: We modelled a multi-chimera subunit vaccine candidate against H. pylori by screening its secretory/outer membrane proteins. We identified B-cell, MHC-II and IFN-γ-inducing epitopes within these proteins. The population coverage, antigenicity, physiochemical properties and secondary structure were evaluated using different in-silico tools, which showed it can be a good and effective vaccine candidate. The 3-D construct was predicted, refined, validated and docked with TLRs. Finally, we performed the molecular docking/simulation and immune simulation studies to validate the stability of interaction and in-silico cloned the epitope sequences into a pET28b(+) plasmid vector. CONCLUSION: The multiepitope-constructed vaccine contains T- cells, B-cells along with IFN-γ inducing epitopes that have the property to generate good cell-mediated immunity and humoral response. This vaccine can protect most of the world's population. The docking study and immune simulation revealed a good binding with TLRs and cell-mediated and humoral immune responses, respectively. Overall, we attempted to design a multiepitope vaccine and expect this vaccine will show an encouraging result against H. pylori infection in in-vivo use.

Biochemical and metabolomic insights into antifungal mechanism of berberine against Candida glabrata.

An unprecedented expansion of antifungal therapy failure incidences in healthcare settings of Candida glabrata is the matter of global concern that needs to be addressed efficiently and effectively. In this pursuit, the present study has investigated the antifungal mechanism of benzylisoquinoline alkaloid berberine using biochemical, metabolic, and gene expression analysis, with the aim to delineate its therapeutic activity against C. glabrata and differentially fluconazole-responsive clinical isolates. Interestingly, the clinical isolates were found to be highly susceptible to berberine. Berberine was found to control the surface properties like hydrophobicity and charge of the cells. The cell membrane composition was altered by berberine, where the ergosterol and fatty acids were affected. The efflux pump activity was inhibited, and osmotic stress was generated in C. glabrata cells upon berberine exposure. The berberine has also generated oxidative stress and activated antioxidant system in C. glabrata cells. Furthermore, these observations were supported by the transcriptional expression study of C. glabrata cell genes (CDR1, RLM1, SLT2, SUR4, KRE1) and metabolomics analysis. Based on fold change analysis, the study identified 20 differential metabolites upon berberine treatment, which belong to central carbon, amino acids, and nucleotide pathways. The checkerboard analysis revealed the potentiation of some classically used antifungal drugs by berberine, thus suggesting it as a combinatorial nutraceutical adjuvant for the eradication of fungal infections. KEY POINTS: • Berberine exhibited better potency against azole-resistant clinical isolates • Berberine modulated metabolites of different pathways • Berberine generated oxidative stress and blocked efflux pump activity.

Unveiling Taenia solium kinome profile and its potential for new therapeutic targets.

Background: Helminth infections cause widespread morbidity and are a significant global disease burden. One among them is Neurocysticercosis, a central nervous system infection caused by the larvae Taenia solium, leading to epilepsy. Helminths are strong immune modulators and can survive for a long time in adverse host environments. Kinases are molecular switches and are essential to initiate/propagate signaling cascades and are detrimental to the regulation of homeostasis. They have been implicated in the progression of many diseases and are potentially lucrative drug targets.Objective: To identify kinases in T. solium proteome and prioritize them as drug targets.Methodology: A Hidden Markov Model (HMM) was used to curate and classify kinases into families based on sequence homology to model organisms followed by phylogenetic analysis of each family. To predict potential drug targets, kinases were identified based on a homologically lethal relationship to C. elegans but non-lethal to humans. Kinases thus selected were searched for matching ligands in SARFkinase and DrugBank databases.Result and conclusion: T. solium kinases make up 1.8% of its proteome, CMGC is the largest kinase family and RGC is the smallest and catalytically inactive family. We predict 23-potential kinases to be drug targets for T. solium.[Figure: see text].

Design and analysis of visible photonics resonators coated with CuO thin film.

The optical and structural properties of CuO film deposited on n-Si via spin-coating method have been ascertained for diverse annealing times. The characterizations were made using x-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), UV-vis spectroscopy, ellipsometry spectroscopy and photoluminescence. A detailed analysis revealed the favorable behavior of CuO film for visible photonics resonators such as Fabry-Perot (FP) and ring resonators. The best suitable property was obtained for a film annealed for 15 min. Accordingly, the CuO-film-coated resonators were simulated and analyzed theoretically using the MODE Solutions tool by Lumerical and MATLAB. In the FP resonator, the transmission intensity, contrast factor and finesse were computed for different annealing times and angles of light incidence. Further, for the CuO ring resonator, an eigenmode solver was incorporated (in the wavelength range 300-900 nm) to compute the effective refractive index, propagation constant, group velocity, losses, dispersion and transmission intensity. Additionally, utilizing the basic expressions, the free spectral range, full-width at half-maximum and quality factor were derived.

Optical and Electrical Characterization of Stable p-Type ZnO Thin Films Obtained by Bismuth Doping.

We report the growth of stable p-type ZnO thin films obtained by doping bismuth (Bi) in ZnO and deposited over ITO coated glass substrate. The Bi doped ZnO thin films have been deposited by a sol-gel spin coating method using zinc acetate and bismuth nitrate as main precursors. The structural, optical and electrical properties of annealed Bi doped thin films have been studied in detail using X-ray diffraction (XRD), Atomic force microscopy (AFM), ellipsometry, hot probe system and Hall measurement. The presence of strong diffraction peak along (101) obtained from the XRD spectra shows that the high-quality Bi doped ZnO nanostructures grow along (101) orientation. A number of important micro-structural parameters for the thin films such as grain size, lattice parameters, stress and texture coefficient have been calculated, in order to show the effect of Bi incorporation in ZnO thin film. Further, transmittance has been calculated over the range of 350- 800 nm wavelength regions. The optical band gap of Bi doped ZnO films have also been calculated for different concentrations of Bi using the data taken by an ellipsometer. Hot probe characterization method has been used to ascertain the type of semiconductor thin film and it was observed that films doped with the concentration of 10 mol% Bi show p-type nature that was found to be stable over the period of eight months. Further, in order to calculate the resistivity, hole concentration, and mobility of p-type Bi doped ZnO thin film Hall measurement have been performed.

Highly reflective Er-doped ZnO thin-film coating for application in a UV optical ring resonator.

We achieved doping-induced optical variation in Erbium-doped ZnO (EZO) that may prove to be a promising material for use in optical ring resonators. EZO thin-film samples were deposited on n-type Si substrate via the sol-gel spin-coating technique followed by annealing in air at 500 °C. The doping-induced morphological variations of the deposited thin film were characterized using x-ray diffraction, ellipsometry, scanning electron microscopy and energy dispersive x-ray spectroscopy. Further, in order to establish the suitability of EZO for optical applications, detailed optical analysis was performed that exhibited that 1 mol% Er-doped ZnO may prove to be suitable material. Finally, a ring resonator design has been proposed using 1 mol% EZO thin film. The proposed structure was simulated using the MODE tool by Lumerical solutions. The Eigenmode Solver has been used to simulate and calculate the effective refractive index, group velocity, propagation constant ß, dispersion and bending losses for a wavelength region of 200 nm to 900 nm. Simplified expressions for the free spectral range, full-width at half-maximum and quality factor have been derived and validated by the simulated data for the proposed ring resonator.

Advances in Skin Regeneration Using Tissue Engineering.

Tissue engineered skin substitutes for wound healing have evolved tremendously over the last couple of years. New advances have been made toward developing skin substitutes made up of artificial and natural materials. Engineered skin substitutes are developed from acellular materials or can be synthesized from autologous, allograft, xenogenic, or synthetic sources. Each of these engineered skin substitutes has their advantages and disadvantages. However, to this date, a complete functional skin substitute is not available, and research is continuing to develop a competent full thickness skin substitute product that can vascularize rapidly. There is also a need to redesign the currently available substitutes to make them user friendly, commercially affordable, and viable with longer shelf life. The present review focuses on providing an overview of advances in the field of tissue engineered skin substitute development, the availability of various types, and their application.

Mutations flanking the carbohydrate binding site of surfactant protein D confer antiviral activity for pandemic influenza A viruses.

We recently reported that a trimeric neck and carbohydrate recognition domain (NCRD) fragment of human surfactant protein D (SP-D), a host defense lectin, with combinatorial substitutions at the 325 and 343 positions (D325A+R343V) exhibits markedly increased antiviral activity for seasonal strains of influenza A virus (IAV). The NCRD binds to glycan-rich viral envelope proteins including hemagglutinin (HA). We now show that replacement of D325 with serine to create D325S+R343V provided equal or increased neutralizing activity compared with D325A+R343V. The activity of the double mutants was significantly greater than that of either single mutant (D325A/S or R343V). D325A+R343V and D325S+R343V also strongly inhibited HA activity, and markedly aggregated, the 1968 pandemic H3N2 strain, Aichi68. D325S+R343V significantly reduced viral loads and mortality of mice infected with Aichi68, whereas wild-type SP-D NCRD did not. The pandemic H1N1 strains of 1918 and 2009 have only one N-linked glycan side on the head region of the HA and are fully resistant to inhibition by native SP-D. Importantly, we now show that D325A+R343V and D325S+R343V inhibited Cal09 H1N1 and related strains, and reduced uptake of Cal09 by epithelial cells. Inhibition of Cal09 was mediated by the lectin activity of the NCRDs. All known human pandemic strains have at least one glycan attachment on the top or side of the HA head, and our results indicate that they may be susceptible to inhibition by modified host defense lectins.

Genetic polymorphism of cytochrome P450 (CYP) 1A1, CYP1A2, and CYP2E1 genes modulate susceptibility to gastric cancer in patients with Helicobacter pylori infection.

BACKGROUND: Activity of cytochrome P450 (CYP), a polymorphic carcinogen-activating enzyme, is exaggerated following Helicobacter pylori infection. We studied the role of CYP2E1, CYP1A2 (rs762551), and CYP1A1 (rs4646903) polymorphisms in association with H. pylori infection in gastric carcinogenesis. METHODS: Genotyping of CYP2E1 (96-bp insertion), CYP1A2 (164A to C), and CYP1A1 (3801C to T) was carried out in 88, 76, 53, and 170 patients with gastric cancer (GC), functional dyspepsia (FD), peptic ulcer (PU), and healthy controls (HC), respectively. Serum IgG antibody (all subjects), rapid urease test, and histology (GC, FD, and PU patients) were used to test for H. pylori. RESULTS: CYP2E1 gene polymorphism was more common among patients with GC than HC and PU [48/88 (54.5 %) vs. 67/170 (39.4 %); OR 1.9, 95 % CI 1.1-3.2, p = 0.016) and [PU 18/53 (34 %); OR 2.3 (1-4.7), p = 0.02]. CYP1A2 CC or CT genotypes was lower among patients with GC than HC [50/88 (56.8 %) vs. 120/170 (70.6 %); OR 0.54 (0.31-0.92), p = 0.023]. CYP1A1 polymorphism and CYP1A1-CYP1A2 haplotypes were comparable among different groups. CYP2E1 was also more common in patients with GC than HC and PU in the absence of H. pylori [33/60 (55 %) vs. 19/52 (36.5 %); OR 4 (1.5-11.4), p = 0.007 and PU 7/22 (31.8 %); OR 3.4 (1-11.6), p = 0.05]. CYP1A1 (CT + TT) was more common in patients with GC than PU in presence of H. pylori [17/26 (65.4 %) vs. 11/29 (38 %); OR 3.0 (1.03-9.3), p = 0.045]. CONCLUSIONS: The presence of CYP2E1 (96-bp insertion) is associated with increased risk of GC even in absence of H. pylori. CYP1A2 CC or CT is associated with reduced risk of GC.

Human H-ficolin inhibits replication of seasonal and pandemic influenza A viruses.

The collectins have been shown to have a role in host defense against influenza A virus (IAV) and other significant viral pathogens (e.g., HIV). The ficolins are a related group of innate immune proteins that are present at relatively high concentrations in serum, but also in respiratory secretions; however, there has been little study of the role of ficolins in viral infection. In this study, we demonstrate that purified recombinant human H-ficolin and H-ficolin in human serum and bronchoalveolar lavage fluid bind to IAV and inhibit viral infectivity and hemagglutination activity in vitro. Removal of ficolins from human serum or bronchoalveolar lavage fluid reduces their antiviral activity. Inhibition of IAV did not involve the calcium-dependent lectin activity of H-ficolin. We demonstrate that H-ficolin is sialylated and that removal of sialic acid abrogates IAV inhibition, while addition of the neuraminidase inhibitor oseltamivir potentiates neutralization, hemagglutinin inhibition, and viral aggregation caused by H-ficolin. Pandemic and mouse-adapted strains of IAV are generally not inhibited by the collectins surfactant protein D or mannose binding lectin because of a paucity of glycan attachments on the hemagglutinin of these strains. In contrast, H-ficolin inhibited both the mouse-adapted PR-8 H1N1 strain and a pandemic H1N1 strain from 2009. H-ficolin also fixed complement to a surface coated with IAV. These findings suggest that H-ficolin contributes to host defense against IAV.

Nanoformulations for dismantling fungal biofilms: The latest arsenals of antifungal therapy.

Globally, fungal infections have evolved as a strenuous challenge for clinicians, particularly in patients with compromised immunity in intensive care units. Fungal co-infection in Covid-19 patients has made the situation more formidable for healthcare practitioners. Surface adhered fungal population known as biofilm often develop at the diseased site to elicit antifungal tolerance and recalcitrant traits. Thus, an innovative strategy is required to impede/eradicate developed biofilm and avoid the formation of new colonies. The development of nanocomposite-based antibiofilm solutions is the most appropriate way to withstand and dismantle biofilm structures. Nanocomposites can be utilized as a drug delivery medium and for fabrication of anti-biofilm surfaces capable to resist fungal colonization. In this context, the present review comprehensively described different forms of nanocomposites and mode of their action against fungal biofilms. Amongst various nanocomposites, efficacy of metal/organic nanoparticles and nanofibers are particularly emphasized to highlight their role in the pursuit of antibiofilm strategies. Further, the inevitable concern of nanotoxicology has also been introduced and discussed with the exigent need of addressing it while developing nano-based therapies. Further, a list of FDA-approved nano-based antifungal formulations for therapeutic usage available to date has been described. Collectively, the review highlights the potential, scope, and future of nanocomposite-based antibiofilm therapeutics to address the fungal biofilm management issue.

Nanosensor based approaches for quantitative detection of heparin.

Heparin, being a widely employed anticoagulant in numerus clinical complications, requires strict quantification and qualitative screening to ensure the safety of patients from potential threat of thrombocytopenia. However, the intricacy of heparin's chemical structures and low abundance hinders the precise monitoring of its level and quality in clinical settings. Conventional laboratory assays have limitations in sensitivity and specificity, necessitating the development of innovative approaches. In this context, nanosensors emerged as a promising solution due to enhanced sensitivity, selectivity, and ability to detect heparin even at low concentrations. This review delves into a range of sensing approaches including colorimetric, fluorometric, surface-enhanced Raman spectroscopy, and electrochemical techniques using different types of nanomaterials, thus providing insights of its principles, capabilities, and limitations. Moreover, integration of smart-phone with nanosensors for point of care diagnostics has also been explored. Additionally, recent advances in nanopore technologies, artificial intelligence (AI) and machine learning (ML) have been discussed offering specificity against contaminants present in heparin to ensure its quality. By consolidating current knowledge and highlighting the potential of nanosensors, this review aims to contribute to the advancement of efficient, reliable, and economical heparin detection methods providing improved patient care.

The human cathelicidin LL-37 inhibits influenza A viruses through a mechanism distinct from that of surfactant protein D or defensins.

LL-37, the only human cathelicidin, is a cationic antimicrobial peptide with antibacterial and antifungal activity. LL-37 is released from neutrophil granules and produced by epithelial cells. It has been implicated in host defence against influenza A virus (IAV) in recent studies. We now demonstrate dose-related neutralizing activity of LL-37 against several seasonal and mouse-adapted IAV strains. The ability of LL-37 to inhibit these IAV strains resulted mainly from direct effects on the virus, since pre-incubation of virus with LL-37 was needed for optimal inhibition. LL-37 bound high-density lipoprotein (HDL), and pre-incubation of LL-37 with human serum or HDL reduced its antiviral activity. LL-37 did not inhibit viral association with epithelial cells as assessed by quantitative RT-PCR or confocal microscopy. This finding contrasted with results obtained with surfactant protein D (SP-D). Unlike collectins or human neutrophil defensins (HNPs), LL-37 did not induce viral aggregation under electron microscopy. In the electron microscopy studies, LL-37 appeared to cause disruption of viral membranes. LL-37 had additive antiviral activity when combined with other innate inhibitors like SP-D, surfactant protein A and HNPs. Unlike HNPs, LL-37 did not bind SP-D significantly. These findings indicate that LL-37 contributes to host defence against IAV through a mechanism distinct from that of SP-D and HNPs.

Nitric oxide-dependent CYP2B degradation is potentiated by a cytokine-regulated pathway and utilizes the immunoproteasome subunit LMP2.

CYP2B proteins in rat hepatocytes undergo NO-dependent proteolytic degradation, but the mechanisms and the reasons for the specificity towards only certain P450 (cytochrome P450) enzymes are yet unknown. In the present study we found that down-regulation of CYP2B proteins by the NO donor NOC-18 is accelerated by pretreatment of the hepatocytes with IL-1 (interleukin-1ß) in the presence of an NO synthase inhibitor, suggesting that an NO-independent action of IL-1 contributes to the lability of CYP2B proteins. The immunoproteasome subunit LMP2 (large multifunctional peptidase 2) was significantly expressed in hepatocytes under basal conditions, and IL-1 induced LMP2 within 6-12 h of treatment. CYP2B protein degradation in response to IL-1 was attenuated by the selective LMP2 inhibitor UK-101, but not by the LMP7 inhibitor IPSI. The results show that LMP2 contributes to the NO-dependent degradation of CYP2B proteins, and suggest that induction of LMP2 may be involved in the potentiation of this degradation by IL-1.

Transport behavior of selected nanoparticles with different surface coatings in granular porous media coated with Pseudomonas aeruginosa biofilm.

Well-controlled laboratory column experiments were conducted to understand the influence of Pseudomonas aeruginosa (P. aeruginosa) biofilms on the transport of selected engineered nanoparticles (ENPs) in granular porous media representative of groundwater aquifers or riverbank filtration settings. To understand the importance of particle size on retention in the biofilm-coated granular (quartz sand) matrix, column experiments were carried out using nanosized (20 nm) and micrometer-sized (1 µm) sulfate-functionalized polystyrene latex particles (designated as 20 nSL and 1 mSL, respectively). Additional experiments conducted with nanosized (20 nm) carboxyl-modified latex particles (20nCL) and carboxyl-modified CdSe/ZnS quantum dots (QDs) provide information on the influence of particle surface chemistry on retention. Biofilm grown on the surface of the sand was characterized by total biomass quantification, confocal laser scanning microscopy (CLSM), and electrokinetic analysis. All four particles exhibit increased retention in the biofilm-coated packed bed: e.g., the attachment efficiency (α) of the 1 mSL particle increases from 0.40 to 1.7, whereas α for the 20 nSL particle increases from 0.04 to 0.10 in the biofilm-coated system. Particle surface chemistry can also influence the affinity of the ENPs for the biofilm coating as revealed by the greater attachment of the 20 nSL particle onto the biofilm-coated sand (α = 0.10) than its carboxylated counterpart (α = 0.04). Column experiments conducted using sand coated with growth medium (LB) or extracellular polymeric substances (EPS) extracted from P. aeruginosa biofilms further reveal that particle surface chemistry influences the interaction between the different ENPs and these coated sand surfaces. Namely, coating of sand surfaces with LB medium or bacterial EPS does not affect the transport of the sulfonated nanoparticle, but the LB coating leads to decreased retention of the carboxylated latex nanoparticle. Furthermore, our results show that EPS coatings are not necessarily good surrogates for biofilm-coated sand. Electrokinetic characterization of the clean and coated sand surfaces also reveals that the extent of particle retention is not controlled by electrical double layer interactions. Future studies should thus be aimed at improving our understanding of the fundamental mechanisms (both colloidal and noncolloidal) governing nanoparticle transport and fate in biofilm-laden granular aquatic environments.

Non-toxicity of water soluble multi-walled carbon nanotube on Escherichia-coli colonies.

Carboxylic acid functionalized water soluble carbon nanotube (wsCNT) shows no toxic effect against the growth of Escherichia-coli (E. coli), a gram-negative bacteria. Treatment up to 8 microg mL(-1) of wsCNT did not show any toxic effect on E. coli growth that was followed by using bacterial growth kinetics and Spread Plate Technique (SPT). The number of E-coli colonies counts with and without wsCNT showed nearly no change and the bacterial growth kinetics in both the cases showing no toxic effect of wsCNT on the growth of E. coli.

REM Sleep Deprivation Alters Learning-Induced Cell Proliferation and Generation of Newborn Young Neurons in the Dentate Gyrus of the Dorsal Hippocampus.

The hippocampus-dependent "trace-appetitive conditioning task" increases cell proliferation and the generation of newborn young neurons. Evidence suggests that adult hippocampal neurogenesis and rapid eye movement (REM) sleep play an essential role in memory consolidation. On the other hand, REM sleep deprivation (REM-SD) induces detrimental effects on training-induced cell proliferation in the hippocampus's dentate gyrus (DG). Nonetheless, the role of REM sleep in the trace-appetitive memory and fate determination of the newly proliferated cells is not known. Here, we have studied the following: (I) the effects of 24 h of REM-SD (soon after training) on trace- and delay-appetitive memory and cell proliferation in the adult DG and (II) the effects of chronic (96 h) REM-SD (3 days after the training, the period in which newly generated cells progressed toward the neuronal lineage) on trace-appetitive memory and the generation of newborn young neurons. We used a modified multiple platform method for the selective REM-SD without altering non-REM (NREM) sleep. We found that 24 h of REM-SD, soon after trace-conditioning, impaired the trace-appetitive memory and the training-induced cell proliferation. Nevertheless, 96 h of REM-SD (3 days after the training) did not impair trace memory. Interestingly, 96 h of REM-SD altered the generation of newborn young neurons. These results suggest that REM sleep plays an essential role in training-induced cell proliferation and the fate determination of the newly generated cells toward the neuronal lineage.

Neuroprotection in glaucoma.

Neuroprotective therapies in glaucoma may play a role in preventing ischemia and oxidative damage that results in apoptosis of retinal ganglion cells and optic nerve damage. Although intraocular pressure (IOP) is the only known modifiable risk factor for glaucoma, disease progression commonly occurs despite IOP control, suggesting that factors other than IOP play a role in its pathogenesis and can potentially act as targets for neuroprotection. Factors including mediators of apoptosis, ischemic changes, poor ocular blood flow and neurotoxins have been hypothesized to play a role in glaucoma progression. Neuroprotective targets include glutamate-induced neurotoxicity, nitric oxidase synthetase, neurotropins, calcium channel receptors, free radicals, vascular insufficiency, the rho-kinase pathway, and more. Drugs related to these factors are being evaluated for their role in neuroprotection, although this area of investigation faces several challenges including limited evidence for these agents' efficacy in clinical studies. Additionally, while IOP-lowering therapies are considered neuroprotective as they generally slow the progress of glaucoma progression, they are limited by the extent of their effect beyond IOP control. The aim of this article is to review the current treatment options available for neuroprotection and to explore the drugs in the pipeline.

Serological assessment of gastric intestinal metaplasia and atrophy using pepsinogen-I, pepsinogen-II and gastrin-17 levels in a low incidence area of gastric cancer endemic for H. pylori infection.

BACKGROUND: Intestinal metaplasia (IM), a precursor of gastric cancer (GC), may be amenable to non-invasive assessment. AIMS: We evaluated the diagnostic utility of serum PG-I, PG-II, PG-I/PG-II ratio and gastrin-17 (G-17) to detect IM and atrophy. METHODS: The study was conducted at a tertiary care center located in low-incidence area of GC, endemic for H. pylori. The evaluation was designed as a prospective case-control study. Patients with GC and dyspepsia were evaluated by endoscopy, histology for IM (H&E, PAS and Alcian blue stains) and H. pylori (H&E and Giemsa stains), rapid urease test and IgG antibody (positive results in any two assays). Serum levels of PG-I, PG-II and G-17 were estimated using ELISA. RESULTS: Of the 98 patients with GC and 62 with dyspepsia, 35 (36%) and 9 (14%) had IM, respectively (p = 0.004). Patients with IM (n = 44) had lower PG-UPG-II ratio than those without IM (n = 116; median 4.4, 0.37-23.6 vs. 6.3, 0.19-38.6, respectively; p = 0.005). A cut-off value of PG-I/PG-II ratio of 6.0 had 64% sensitivity and 52% specificity for detecting IM (area under ROC curve 0.64). 26/44 (60%) patients with IM and 52/98 (53%) with GC had PG-I/PG-II ratio < 6. Serum G-17 was comparable among patients with and without IM. CONCLUSIONS: Though the PG-I/PG-II ratio was lower in patients with IM, only 60% had a lower ratio suggesting that this test and G-17 may not be useful to detect IM in low-incidence areas of GC, endemic for H. pylori infection.