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Introduction: Spleen tyrosine kinase (SYK), a nonreceptor tyrosine kinase, has emerged as a vital component in the complex symphony of cancer cell survival and division. SYK activation (constitutive) is documented in various B-cell malignancies, and its inhibition induces programmed cell death. In some instances, it also acts as a tumor suppressor., Areas Covered: Involvement of the SYK in the cancer growth, specifically in the progression of chronic lymphocytic leukemia (CLL), diffuse large B cell lymphomas (DLBCLs), acute myeloid leukemia (AML), and multiple myeloma (MM) is discussed. Therapeutic strategies to target SYK in cancer, including investigational SYK inhibitors, combinations of SYK inhibitors with other drugs targeting therapeutically relevant targets, and recent advancements in constructing new structural assemblages as SYK inhibitors, are also covered., Expert Opinion: The SYK inhibitor field is currently marred by the poor translation rate of SYK inhibitors from preclinical to clinical studies. Also, dose-limited toxicities associated with the applications of SYK inhibitors have been evidenced. Thus, the development of new SYK inhibitory structural templates is in the need of the hour. To accomplish the aforementioned, interdisciplinary teams should incessantly invest efforts to expand the size of the armory of SYK inhibitors.

Attempts to furnish antitumor structural templates that can prevent the occurrence of drug-induced hyperuricemia spurred us to generate xanthine oxidase inhibitor-based hydroxamic acids and anilides. Specifically, the design strategy involved the insertion of febuxostat (xanthine oxidase inhibitor) as a surface recognition part of the HDAC inhibitor pharmacophore model. Investigation outcomes revealed that hydroxamic acid 4 elicited remarkable antileukemic effects mediated via HDAC isoform inhibition. Delightfully, the adduct retained xanthine oxidase inhibitory activity, though xanthine oxidase inhibition was not the underlying mechanism of its cell growth inhibitory effects. Also, compound 4 demonstrated significant in-vivo anti-hyperuricemic (PO-induced hyperuricemia model) and antitumor activity in an HL-60 xenograft mice model. Compound 4 was conjugated with poly (ethylene glycol) poly(aspartic acid) block copolymer to furnish pH-responsive nanoparticles (NPs) in pursuit of circumventing its cytotoxicity towards the normal cell lines. SEM analysis revealed that NPs had uniform size distributions, while TEM analysis ascertained the spherical shape of NPs, indicating their ability to undergo self-assembly. HDAC inhibitor 4 was liberated from the matrix due to the polymeric nanoformulation's pH-responsiveness, and the NPs demonstrated selective cancer cell targeting ability., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Careful recruitment of the components of the HDAC inhibitory template culminated in veliparib-based anilide 8 that elicited remarkable cell growth inhibitory effects against HL-60 cell lines mediated via dual modulation of PARP [(IC 50 (PARP1) = 0.02 nM) and IC 50 (PARP2) = 1 nM)] and HDACs (IC 50 value = 0.05, 0.147 and 0.393 μM (HDAC1, 2 and 3). Compound 8 downregulated the expression levels of signatory biomarkers of PARP and HDAC inhibition. Also, compound 8 arrested the cell cycle at the G0/G1 phase and induced autophagy. Polymer nanoformulation (mPEG-PCl copolymeric micelles loaded with compound 8) was prepared by the nanoprecipitation technique. The mPEG-PCL diblock copolymer was prepared by ring-opening polymerization method using stannous octoate as a catalyst. The morphology of the compound 8@mPEG-PCL was examined using TEM and the substance was determined to be monodispersed, spherical in form, and had an average diameter of 138 nm. The polymer nanoformulation manifested pH-sensitive behaviour as a greater release of compound 8 was observed at 6.2 pH as compared to 7.4 pH mimicking physiological settings. The aforementioned findings indicate that the acidic pH of the tumour microenvironment might stimulate the nanomedicine release which in turn can attenuate the off-target effects precedentially claimed to be associated with HDAC inhibitors., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

One of the major challenges on the way to low-cost, simple, and effective cancer treatments is the lack of smart anticancer drug delivery materials with the requisite of site-specific and microenvironment-responsive properties. This work reports the development of plasma-engineered smart drug nanocarriers (SDNCs) containing chitosan and nitrogen-doped graphene quantum dots (NGQDs) for drug delivery in a pH-responsive manner. Through a customized microplasma processing, a highly cross-linked SDNC with only 4.5% of NGQD ratio can exhibit enhanced toughness up to threefold higher than the control chitosan group, avoiding the commonly used high temperatures and toxic chemical cross-linking agents. The SDNCs demonstrate improved loading capability for doxorubicin (DOX) via π-π interactions and stable solid-state photoluminescence to monitor the DOX loading and release through the Förster resonance energy transfer (FRET) mechanism. Moreover, the DOX loaded SDNC exhibits anticancer effects against cancer cells during cytotoxicity tests at minimum concentration. Cellular uptake studies confirm that the DOX loaded SDNC can be successfully internalized into the nucleus after 12 h incubation period. This work provides new insights into the development of smart, environmental-friendly, and biocompatible nanographene hydrogels for the next-generation biomedical applications., (© 2023 Wiley-VCH GmbH.)

A fragment recruitment process was conducted to pinpoint a suitable fragment for installation in the HDAC inhibitory template to furnish agents endowed with the potential to treat lung cancer. Resultantly, Ring C expanded deoxyvasicinone was selected as an appropriate surface recognition part that was accommodated in the HDAC three-component model. Delightfully, fused quinazolinone 6 demonstrating a magnificent anticancer profile against KRAS and EGFR mutant lung cancer cell lines (IC 50  = 0.80-0.96 μM) was identified. Results of the mechanistic studies confirmed that the cell growth inhibitory effects of compound 6 stems for HDAC6 (IC 50  = 12.9 nM), HDAC1 (IC 50  = 49.9 nM) and HDAC3 inhibition (IC 50  = 68.5 nM), respectively. Compound 6 also suppressed the colony formation ability of A549 cells, induced apoptosis, and increased autophagic flux. Key interactions of HDAC inhibitor 6 within the active site of HDAC isoforms were figured out through molecular modeling studies. Furthermore, a pH-responsive nanocarrier (Hyaluronic acid - fused quinazolinone 6 nanoparticles) was designed and assessed using a dialysis bag approach under both normal and acidic circumstances that confirmed the pH-sensitive nature of NPs. Delightfully, the nanoparticles demonstrated selective cell viability reduction potential towards the lung cancer cell lines (A549 lung cancer cell lines) and were found to be largely devoid of cell growth inhibitory effects under normal settings (L929, mouse fibroblast cells)., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Freshwater mussels cannot spread through oceanic barriers and represent a suitable model to test the continental drift patterns. Here, we reconstruct the diversification of Oriental freshwater mussels (Unionidae) and revise their taxonomy. We show that the Indian Subcontinent harbors a rather taxonomically poor fauna, containing 25 freshwater mussel species from one subfamily (Parreysiinae). This subfamily most likely originated in East Gondwana in the Jurassic and its representatives arrived to Asia on two Gondwanan fragments (Indian Plate and Burma Terrane). We propose that the Burma Terrane was connected with the Indian Plate through the Greater India up to the terminal Cretaceous. Later on, during the entire Paleogene epoch, these blocks have served as isolated evolutionary hotspots for freshwater mussels. The Burma Terrane collided with mainland Asia in the Late Eocene, leading to the origin of the Mekong's Indochinellini radiation. Our findings indicate that the Burma Terrane had played a major role as a Gondwanan "biotic ferry" alongside with the Indian Plate., (© 2022. The Author(s).)

Hyaluronic acid (HA) is conjugated with BHQ3 moiety with azo bonds to prepare hypoxia-responsive polymer conjugate. Because of the amphiphilic nature, the polymer conjugate self-assembles to HA-BHQ3 nanoparticles (NPs). The anticancer drug doxorubicin (DOX) is loaded into the NPs. In the physiological environment, DOX is released slowly. In contrast, under hypoxic conditions, the azo bond in BHQ3 is cleaved, thus significantly enhancing the DOX release rate. For instance, after 24 h, 25% of DOX is released under normal conditions, while 74% of DOX is released under hypoxic conditions. In vitro cytotoxicity demonstrates higher toxicity in the hypoxic conditions. DOX@HA-BHQ3 NPs exhibit greater toxicity levels against 4T1 cells in hypoxic conditions. The fluorescent microscope images confirm the oxygen-dependent intracellular DOX release from the NPs. The in vivo biodistribution results suggest the tumor targetability of HA-BHQ3 NPs in 4T1 tumor-bearing mice.

Carbohydrate functionalized polymers or Glycopolymers have earned a great deal of interest in recent times for their potential biomedical applications. In the present study, a mannose containing glycopolymer was synthesized by cyclopolymerization of malonic acid derivative using second generation Hoveyda Grubbs' catalyst. Post-polymerization modification was done to install a propargyl moiety. Finally, functionalization of the propargylated polymer with 2-azidoethyl mannoside using azide-alkyne "click chemistry" furnished the target glycopolymer which was successfully characterized using NMR, FT-IR, mass spectroscopy and advanced polymer chromatography. The glycopolymer was found to self-assemble into capsule and spherical shape in water and DMSO respectively and these morphologies were observed through SEM and TEM. Upon interaction with Con A, the mannose containing glycopolymer showed an increment in aggregation induced fluorescence with increasing concentration of the lectin. In vitro cytotoxicity studies on MCF 7 cell line showed 90% cell viability up to glycopolymer concentration of 500 μg/mL., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

A pH-responsive smart nanocarrier with significant components was synthesized by conjugating the non-emissive anticancer drug methyl orange and polyethylene glycol derived folate moiety to the backbone of polynorbornene. Complete synthesis procedure and characterization methods of three monomers included in the work: norbornene-derived Chlorambucil (Monomer 1), norbornene grafted with polyethylene glycol, and folic acid (Monomer 2) and norbornene attached methyl orange (Monomer 3) connected to the norbornene backbone through ester linkage were clearly discussed. Finally, the random copolymer CHO PEG FOL METH was synthesized by ring-opening metathesis polymerization (ROMP) using Grubbs' second-generation catalyst. Advanced polymer chromatography (APC) was used to find the final polymer's molecular weight and polydispersity index (PDI). Dynamic light scattering, scanning electron microscopy (SEM), and transmission electron microscopy (TEM) were utilized to explore the prodrug's size and morphology. Release experiments of the anticancer drug, Chlorambucil and the coloring agent, methyl orange, were performed at different pH and time. Cell viability assay was carried out for determining the rate of survived cells, followed by the treatment of our final polymer named CHO PEG FOL METH., (© 2021 Wiley-VCH GmbH.)

Background: . Implementation of healthcare regulatory policies, especially in low- and middle-income countries where the private health sector is predominant, is challenging. Karnataka, a southern state in India, enacted the Karnataka Private Medical Establishments Act (KPMEA) with an aim to ensure quality of care in the private healthcare establishments. After more than a decade the implementation of KPMEA is suboptimal., Methods: . We used a case study design. The case was 'implementation of KPMEA'. The case study site was Bengaluru Urban district in Karnataka. Data from key informant interviews, focus group discussions held at the state, district and subdistrict levels and key policy documents, minutes of the meetings, data from the State Department of Health and Family Welfare, district level KPMEA data and litigations at the High Court of Karnataka were analysed using a framework., Results: . The policy (KPMEA) content is inadequate and requires clarity in certain provisions of the Act. There was a lack of coordination between the implementing agencies. Workforce shortages were evident. Factors that impede the enforcement of the Act include poor knowledge and lack of competency of the officials on the content and the implementation mechanics of the policy, insufficient policy oversight from the state on the districts, corruption, political interference and lack of support from the local public, especially during raids on illegal establishments., Conclusions: . A regulatory policy such as KPMEA needs a clear, comprehensive content and directions for operationalization. However, improving the content of the policy is not easy as some aspects of the policy remain contentious with the private healthcare providers/ establishments. Addressing health governance issues at all levels is key to effective enforcement., Competing Interests: None

Competing Interests: Competing interests: None declared.

India's rapid economic growth has been accompanied by slower improvements in population health. Given the need to reconcile the ambitious goal of achieving Universal Coverage with limited resources, a robust priority-setting mechanism is required to ensure that the right trade-offs are made and the impact on health is maximised. Health Technology Assessment (HTA) is endorsed by the World Health Assembly as the gold standard approach to synthesizing evidence systematically for evidence-informed priority setting (EIPS). India is formally committed to institutionalising HTA as an integral component of the EIPS process. The effective conduct and uptake of HTA depends on a well-functioning ecosystem of stakeholders adept at commissioning and generating policy-relevant HTA research, developing and utilising rigorous technical, transparent, and inclusive methods and processes, and a strong multisectoral and transnational appetite for the use of evidence to inform policy. These all require myriad complex and complementary capacities to be built at each level of the health system . In this paper we describe how a framework for targeted and locally-tailored capacity building for EIPS, and specifically HTA, was collaboratively developed and implemented by an international network of priority-setting expertise, and the Government of India., (© 2020 The Authors.)

Owing to their unique biological functions, hyaluronic acid (HA) and its derivatives have been explored extensively for biomedical applications such as tissue engineering, drug delivery, and molecular imaging. In particular, self-assembled HA nanoparticles (HA-NPs) have been used widely as target-specific and long-acting nanocarriers for the delivery of a wide range of therapeutic or diagnostic agents. Recently, it has been demonstrated that empty HA-NPs without bearing any therapeutic agent can be used therapeutically for the treatment of inflammatory diseases via modulating inflammatory responses. In this review, we aim to provide an overview of the significant achievements in this field and highlight the potential of HA-NPs for the treatment of inflammatory diseases.

The conventional chemotherapeutic agents, used for cancer chemotherapy, have major limitations including non-specificity, ubiquitous biodistribution, low concentration in tumor tissue, and systemic toxicity. In recent years, owing to their unique features, polymeric nanoparticles have been widely used for the target-specific delivery of drugs in the body. Although polymeric nanoparticles have addressed a number of important issues, the bioavailability of drugs at the disease site, and especially upon cellular internalization, remains a challenge. A polymer nanocarrier system with a stimuli-responsive property (e.g., pH, temperature, or redox potential), for example, would be amenable to address the intracellular delivery barriers by taking advantage of pH, temperature, or redox potentials. With a greater understanding of the difference between normal and pathological tissues, there is a highly promising role of stimuli-responsive nanocarriers for drug delivery in the future. In this review, we highlighted the recent advances in different types of stimuli-responsive polymers for drug delivery.

Trop2, a transmembrane glycoprotein, has emerged as a biomarker for targeted cancer therapy since it is overexpressed in 80% of triple negative breast cancer (TNBC) patients. For the site-specific delivery of the anticancer drug into TNBC, anti-Trop2 antibody-conjugated nanoparticles (ST-NPs) were prepared as the potential nanocarrier, composed of carboxymethyl dextran (CMD) derivatives with bioreducible disulfide bonds. Owing to its amphiphilicity, the CMD derivatives were self-assembled into nano-sized particles in an aqueous condition. Doxorubicin (DOX), chosen as a model anticancer drug, was effectively encapsulated into the nanoparticles. DOX-loaded ST-NPs (DOX-ST-NPs) rapidly released DOX in the presence of 10mM glutathione (GSH), whereas the DOX release is significantly retarded in the physiological condition (PBS, pH 7.4). Confocal microscopic images and flow cytometry analysis demonstrated that DOX-ST-NPs were selectively taken up by MDA-MB-231 as the representative Trop2-expressing TNBC cells. Consequently, DOX-ST-NPs exhibited higher toxicity to Trop2-positive MDA-MB-231 cancer cells, compared to DOX-loaded control nanoparticles without the disulfide bond or anti-Trop2 antibody. Overall, ST-NPs might be a promising carrier of DOX for targeted TNBC therapy., (Copyright © 2017. Published by Elsevier B.V.)

In an attempt to develop the hypoxia-responsive nanoparticles for cancer therapy, a polymer conjugate, consisting of carboxymethyl dextran (CMD) and black hole quencher 3 (BHQ3), was prepared. The polymer conjugate can self-assemble into nanoparticles (CMD-BHQ3 NPs) under aqueous conditions. The anticancer drug, doxorubicin (DOX), was loaded in CMD-BHQ3 NPs to prepare DOX@CMD-BHQ3 NPs. The CMD-BHQ3 NPs released DOX in a sustained manner under physiological conditions, whereas the release rate of DOX remarkably increased under hypoxic conditions throughout the cleavage of the azo bond in BHQ3. In vitro cytotoxicity study revealed that DOX@CMD-BHQ3 NPs showed higher toxicity under hypoxic conditions than normoxic conditions. Confocal microscopic images indicated oxygen-dependent intracellular release of DOX from DOX@CMD-BHQ3. In vivo biodistribution study demonstrated that CMD-BHQ3 NPs were preferentially accumulated in the tumor after systemic administration into tumor-bearing mice. Overall, CMD-BHQ3 might be a promising carrier for selective drug release in the hypoxic tumor., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Conventional cancer targeting with nanoparticles has been based on the assumed enhanced permeability and retention (EPR) effect. The data obtained in clinical trials to date, however, have rarely supported the presence of such an effect. To address this challenge, we formulated intracellular nitric oxide-generating nanoparticles (NO-NPs) for the tumor site-specific delivery of NO, a well-known vasodilator, with the intention of boosting EPR. These nanoparticles are self-assembled under aqueous conditions from amphiphilic copolymers of poly(ethylene glycol) and nitrated dextran, which possesses inherent NO release properties in the reductive environment of cancer cells. After systemic administration of the NO-NPs, we quantitatively assessed and visualized increased tumor blood flow as well as enhanced vascular permeability than could be achieved without NO. Additionally, we prepared doxorubicin (DOX)-encapsulated NO-NPs and demonstrated consequential improvement in therapeutic efficacy over the control groups with considerably improved DOX intratumoral accumulation. Overall, this proof of concept study implies a high potency of the NO-NPs as an EPR enhancer to achieve better clinical outcomes.

Thrombocytopenia is a significant complication of chemotherapy and radiation therapy. Platelet factor 4 (PF4; CXCL4) is a negative paracrine of megakaryopoiesis. We have shown that PF4 levels are inversely related to steady-state platelet counts, and to the duration and severity of chemotherapy- and radiation-induced thrombocytopenia (CIT and RIT, respectively). Murine studies suggest that blocking the effect of PF4 improves megakaryopoiesis, raising nadir platelet counts and shortening the time to platelet count recovery. We examined the ability of 2-O, 3-O desulfated heparin (ODSH), a heparin variant with little anticoagulant effects, to neutralize PF4's effects on megakaryopoiesis. Using megakaryocyte colony assays and liquid cultures, we show that ODSH restored megakaryocyte proliferation in PF4-treated Cxcl4 -/- murine and human CD34 + -derived megakaryocyte cultures (17.4% megakaryocyte colonies, P < .01 compared with PF4). In murine CIT and RIT models, ODSH, started 24 hours after injury, was examined for the effect on hematopoietic recovery demonstrating higher platelet count nadirs (9% ± 5% treated vs 4% ± 4% control) and significantly improved survival in treated animals (73% treated vs 36% control survival). Treatment with ODSH was able to reduce intramedullary free PF4 concentrations by immunohistochemical analysis. In summary, ODSH mitigated CIT and RIT in mice by neutralizing the intramedullary negative paracrine PF4. ODSH, already in clinical trials in humans as an adjuvant to chemotherapy, may be an important, clinically relevant therapeutic for CIT and RIT., (© 2018 by The American Society of Hematology.)

Hypoxia, or low oxygen tension, is a common feature of solid tumors. Here, we report hypoxia-responsive mesoporous silica nanoparticles (HR-MSNs) with a 4-nitroimidazole-β-cyclodextrin (NI-CD) complex that is acting as the hypoxia-responsive gatekeeper. When these CD-HR-MSNs encountered a hypoxic environment, the nitroimidazole (NI) gatekeeper portion of CD-HR-MSNs disintegrated through bioreduction of the hydrophobic NI state to the hydrophilic NI state. Under hypoxic conditions, the release rate of doxorubicin (DOX) from DOX-loaded CD-HR-MSNs (DOX-CD-HR-MSNs) increased along with the disintegration of the gatekeeper. Conversely, DOX release was retarded under normoxic conditions. In vitro experiments confirmed that DOX-CD-HR-MSNs exhibit higher toxicity to hypoxic cells when compared to normoxic cells. Confocal microscopy images indicated that DOX-CD-HR-MSNs effectively release DOX into SCC-7 cells under hypoxic conditions. These results demonstrate that CD-HR-MSNs can release drugs in a hypoxia-responsive manner, and thus are promising drug carriers for hypoxia-targeted cancer therapy., Competing Interests: The authors have no conflicts of interest to declare.

Huntington's Disease (HD) is a neurodegenerative disorder caused by an expansion in a CAG-tri-nucleotide repeat that introduces a poly-glutamine stretch into the huntingtin protein (mHTT). Mutant huntingtin (mHTT) has been associated with several phenotypes including mood disorders and depression. Additionally, HD patients are known to be more susceptible to type II diabetes mellitus (T2DM), and HD mice model develops diabetes. However, the mechanism and pathways that link Huntington's disease and diabetes have not been well established. Understanding the underlying mechanisms can reveal potential targets for drug development in HD. In this study, we investigated the transcriptome of mHTT cell populations alongside intracellular glucose measurements using a functionalized nanopipette. Several genes related to glucose uptake and glucose homeostasis are affected. We observed changes in intracellular glucose concentrations and identified altered transcript levels of certain genes including Sorcs1, Hh-II and Vldlr . Our data suggest that these can be used as markers for HD progression. Sorcs1 may not only have a role in glucose metabolism and trafficking but also in glutamatergic pathways affecting trafficking of synaptic components.

Introduction: The government of India introduced a tobacco control legislation in 2003 and is a party to the WHO Framework Convention on Tobacco Control. However, anecdotal evidence points to the government's conflicting interests in tobacco control and trade. This research seeks to scope instances of conflicts of interests within the government and analyse how they operate in the Indian context., Methods: We conducted an exploratory study analysing documents over a 2-year period. We scanned media reports related to tobacco, documents of the tobacco industry, information retrieved from governments using the Right to Information Act and relevant websites. The data were analysed through thematic coding., Results: 100 instances of conflicts of interest were found and classified under six categories: public support for the tobacco industry by government institutions or individuals; stakeholding or ownership of tobacco companies by government functionaries; individuals holding positions both in tobacco companies and the government; formal partnerships between the tobacco industry and public agencies; conflicting policies; and incentives available for the tobacco industry. These instances occur at all three levels of government: the individual, institutional and policy levels., Conclusions: Conflicts of interest are rampant in India and operate in many different ways. These conflicts can lead to negative consequences for tobacco control with far-reaching effects. Varied strategies using legal, administrative and legislative tools need to be adopted to manage conflicts of interest., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Background: Periodontitis is characterized by microbial infection, inflammation, tissue breakdown, and accelerated loss of alveolar bone matrix. Treatment targeting these multiple stages of the disease provides ways to treat or prevent periodontitis. Certain glycosaminoglycans (GAGs) block multiple inflammatory mediators as well as suppress bacterial growth, suggesting that these GAGs may be exploited as a therapeutic for periodontitis., Methods: We investigated the effects of a synthetic GAG, GM-0111, on various molecular events associated with periodontitis: growth of Porphyromonas gingivalis (P. gingivalis) and Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans) pathogenic bacteria associated with periodontitis; activation of pro-inflammatory signaling through TLR2 and TLR4 in mouse macrophage RAW 264.7 cells and heterologously expressed HEK 293 cells; osteoclast formation and bone matrix resorption in cultured mouse pre-osteoclasts., Results: (1) GM-0111 suppressed the growth of P. gingivalis and A. actinomycetemcomitans even at 1% (w/v) solution. The antibacterial effects of GM-0111 were stronger than hyaluronic acid (HA) or xylitol in P. gingivalis at all concentrations and comparable to xylitol in A. actinomycetemcomitans at ≥2% (w/v) solution. We also observed that GM-0111 suppressed biofilm formation of P. gingivalis and these effects were much stronger than HA. (2) GM-0111 inhibited TLR-mediated pro-inflammatory cellular signaling both in macrophage and HEK 293 cells with higher selectivity for TLR2 than TLR4 (IC50 of 1-10 ng/mL vs. > 100 μg/mL, respectively). (3) GM-0111 blocked RANKL-induced osteoclast formation (as low as 300 ng/mL) and bone matrix resorption. While GM-0111 showed high affinity binding to RANKL, it did not interfere with RANKL/RANK/NF-κB signaling, suggesting that GM-0111 inhibits osteoclast formation by a RANKL-RANK-independent mechanism., Conclusions: We report that GM-0111 inhibits multiple molecular events involved in periodontitis, spanning from the early pro-inflammatory TLR signaling, to pathways activated at the later stage component of bone loss.

Liquid crystal (LC) materials are currently the dominant electronic materials in display technology because of the ease of control of molecular orientation using an electric field. However, this technology requires the fabrication of two polarizers to create operational displays, reducing light transmission efficiency below 10%. It is therefore desirable to develop new technologies to enhance the light efficiency while maintaining or improving other properties such as the modulation speed of the molecular orientation. Here we report a uniaxial-oriented B7 smectic liquid crystalline film, using fluorescent bent-core LC molecules, a chemically modified substrate, and an in-plane electric field. A LC droplet under homeotropic boundary conditions of air/LC as well as LC/substrate exhibits large focal conic like optical textures. The in-plane electric field induced uniaxial orientation of the LC molecules, in which molecular polar directors are aligned in the direction of the electric field. This highly oriented LC film exhibits linearly polarized luminescence and microsecond time-scale modulation characteristics. The resultant device is both cheap and easy to fabricate and thus has great potential for electro-optic applications, including LC displays, bioimaging systems, and optical communications.

CaS:Ce(3+) is an efficient green-emitting (535 nm) phosphor, excitable with blue light (450-470 nm) and was synthesized via a solid-state reaction method by heating under a reducing atmosphere. The luminescent properties, photoluminescent (PL) excitation and emission of the phosphor were analyzed by spectrofluorophotometry. The excitation and emission peaks of the CaS:Ce(3+) phosphor lay in the visible region, which made them relevant for light-emitting diode (LED) application for the generation of white light. Judd-Oflet parameters were calculated and revealed that green light emitted upon blue illumination. The prepared phosphor had strong blue absorption at 470 nm and a broad green emission band range from 490-590 nm with the peak at 537 nm. The characteristics of the CaS:Ce(3+) phosphor make it suitable for use as a wavelength tunable green emitting phosphor for three band white LEDs pumped by a blue LED (470 nm). The Commission International de l'Eclairage co-ordinates were calculated by a spectrophotometric method using the spectral energy distribution (0.304, 0.526) and confirm the green emission. The potential application of this phosphor is as a phosphor-converted white light-emitting diode., (Copyright © 2015 John Wiley & Sons, Ltd.)

Introduction: Hyaluronic acid (HA) has emerged as a promising applicant for the tumor-targeted delivery of various therapeutic agents. Because of its biocompatibility, biodegradability and receptor-binding properties, HA has been extensively investigated as the drug delivery carrier. In this review, recent advances in HA-based nanomedicines are discussed., Areas Covered: This review focuses on HA-based nanomedicines for the diagnosis and treatment of cancer. In particular, recent advances in HA-drug conjugates and HA-based nanoparticles for small molecular drug delivery are discussed. The bioreducible HA conjugates for small interfering ribonucleic acid delivery have been also discussed., Expert Opinion: To develop a successful HA-based nanomedicine, it has to be prepared without significant deterioration of intrinsic property of HA. The chemical modification of HA with drugs or hydrophobic moieties may reduce the binding affinity of HA to the receptors. In addition, since the HA-based nanomedicines tend to accumulate in the liver after their systemic administration, new strategies to overcome this issue have to be developed.

Semen was collected from six dromedary camels using artificial vagina during rutting season. Liquefaction of the viscous semen occurred in 23.89 ± 1.49 h. During liquefaction, proteins with molecular masses of 24.55 kDa and 22.07 kDa appeared in conjunction with the disappearance of intact 26.00 kDa protein after 18-24 h. These proteins were identified as β-nerve growth factors (β-NGFs) in liquefied camel semen. Guanidine-HCL improves the rheological characteristics of dromedary camel semen along with significant (P < 0.01) increase in sperm motility. No significant differences were found in viability of spermatozoa indicating no visible detrimental effects on spermatozoa. The cause of semen viscosity, as well as proteins that are present in liquefied dromedary camel seminal plasma, is described for the first time.

In this density functional theory based investigation, we have modelled and studied the adsorption behaviour of guanidinium cations and substituted (phenyl, methoxy phenyl, nitro phenyl and di-nitro phenyl) guanidinium cationic collectors on the basal surfaces of kaolinite and goethite. The adsorption behaviour is assessed in three different media, such as gas, explicit water and pH medium, to understand the affinity of GC collectors to the SiO4 tetrahedral and AlO6 octahedral surfaces of kaolinite. The tetrahedral siloxane surface possesses a larger binding affinity to GC collectors than the octahedral sites due to the presence of surface exposed oxygen atoms that are active in the intermolecular interactions. Furthermore, the inductive electronic effects of substituted guanidinium cations also play a key role in the adsorption mechanism. Highly positive cations result in a stronger electrostatic interaction and preferential adsorption with the kaolinite surfaces than low positive cations. Computed interaction energies and electron densities at the bond critical points suggest that the adsorption of guanidinium cations on the surfaces of kaolinite and goethite is due to the formation of intra/inter hydrogen bonding networks. Also, the electrostatic interaction favours the high adsorption ability of GC collectors in the pH medium than gas phase and water medium. The structures and energies of GC collectors pave an intuitive view for future experimental studies on mineral flotation.

The B7 phases of bent-core molecules are polarization splay modulated fluid smectics that exhibit an unusually complex variety of exotic macroscopic structures, textures, and defects visible in polarized light microscopy. Herein we describe optical studies of these structures using fluorescence confocal polarizing microscopy (FCPM) and depolarized transmission optical microscopy to probe their organization in three dimensions. These experiments utilize recently reported fluorescent bent-core molecules designed to give strong polarized fluorescence. This new bent-core molecular family provides the means for probing a variety of bent-core phases and structures by using FCPM and multiphoton fluorescence nonlinear imaging techniques. Comparative textural analysis of the B7 structures obtained using different types of imaging and the corresponding structural models are discussed., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

New porphyrin sensitizers based on donor-π-acceptor (D-π-A) approach have been designed, synthesized, characterized by various spectroscopic techniques and their photovoltaic properties explored. N,N'-Diphenylamine acts as donor, the porphyrin is the π-spacer, and either carboxylic acid or cyanoacryclic acid acts as acceptor. All compounds were characterized by using (1)H NMR spectroscopy, ESI-MS, UV-visible emission spectroscopies as well as electrochemical methods. The presence of aromatic groups between porphyrin π-plane and acceptor group push the absorption of both Soret and Q-bands of porphyrin towards the red region. The electrochemical properties suggests that LUMO of these sensitizers above the TiO2 conduction band. Finally, the device was fabricated using liquid redox electrolyte (I(-)/I3(-)) and its efficiency was compared with that of a leading sensitizer., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Vibrio vulnificus, an important food-borne pathogen, is known to enter viable but nonculturable (VBNC) state under low temperature and low nutrition stress conditions. Present study examined the time required for induction of VBNC state and temperature which induces resuscitation of V. vulnificus YJ016. The change in cell morphology and gene expression during VBNC state and in resuscitated cells was also examined. V. vulnificus incubated in artificial sea water at 4 °C entered VBNC state after considerably extended time (70 days). An increase in temperature by 6 °C from the VBNC induction temperature (4 °C) resulted in resuscitation of VBNC cells; however, maximum resuscitation was observed when VBNC cells were held at 23 °C for 24 h. VBNC cells changed their morphology from comma shape to coccoid shape. Two rounds of induction of VBNC and resuscitation were possible with V. vulnificus cells; however, there was progressive reduction in number of resuscitated cells and after 190 days cells failed to resuscitate. Significant up-regulation of genes related to membrane proteins [porinH (10.4-fold), ompU (2.9-fold)], regulatory proteins [envZ (5.6-fold), toxR (4.5-fold), toxS (4.8-fold)], oxidative stress related protein katG (2.3-fold), cell division/maintenance proteins [ftsZ (4.3), mreB (6.5-fold)] and resuscitating promoter factor yeaZ (fourfold) was observed during resuscitation with respect to VBNC state indicating that these genes play a role during resuscitation. Gene expression data presented here would enhance our understanding of resuscitation of V. vulnificus from VBNC state. The results also highlight the importance of maintenance of low temperature during storage of seafood.

Nosocomial pneumonia (NP, or hospital-acquired pneumonia) is associated with infections originating from hospital-borne pathogens. Persistent microbial presence and acute lung injury are common features of these infections, contributing to the high mortality rates and excessive financial burden for these patients. Pseudomonas aeruginosa (PA), a gram-negative opportunistic pathogen, is one of the prominent pathogens associated with NP. PA pneumonia is characterized by excessive secretion of inflammatory cytokines, neutrophil infiltration, and subsequent lung damage. The persistent presence of PA along with overwhelming inflammatory response is suggestive of impairment in innate immunity. High mobility group box 1 (HMGB1), a recently discovered potent pro-inflammatory cytokine, plays an important role in PA lung infections by compromising innate immunity via impairing phagocyte function through toll-like receptors (TLR) TLR2 and TLR4. ODSH (2-O, 3-O-desulfated heparin), a heparin derivative with significant anti-inflammatory properties but minimal anti-coagulatory effects, has been shown to reduce neutrophilic lung injury in the absence of active microbial infections. This study examined the effects of ODSH on PA pneumonia. This study demonstrates that ODSH not only reduced PA-induced lung injury, but also significantly increased bacterial clearance. The ameliorated lung injury, together with the increased bacterial clearance, resulted in marked improvement in the survival of these animals. The resulting attenuation in lung injury and improvement in bacterial clearance were associated with decreased levels of airway HMGB1. Furthermore, binding of HMGB1 to its receptors TLR2 and TLR4 was blunted in the presence of ODSH. These data suggest that ODSH provides a potential novel approach in the adjunctive treatment of PA pneumonia.

Background: The aim of this study is to evaluate the dimensional accuracy of heat polymerized PMMA denture base clamped by the conventional method and by R.S technique and cured by a different curing cycle., Materials & Methods: In this study, a total of 40 standardized maxillary record bases were fabricated with seven reference points: Point A - Incisive papilla, Point B & C - Canine region on either side, Point E & G - Midpoint of tuberosities on either side, Point F- Midpoint of the line joining the two tuberosities, Point D- Midpoint between the line joining A and F. Group A: Ten maxillary record bases were fabricated by conventional clamping method and cured by long curing cycle. Group A1: Ten maxillary record bases were fabricated by R.S tension clamping method and cured by long curing cycle. Group B: Ten maxillary record bases were fabricated by conventional clamping method and cured by short curing cycle. Group B1: Ten maxillary record bases were fabricated by R.S tension clamping method and cured by short curing cycle. The distances between the reference points i.e. A-B, A-C, A-D, D-F, B-E, C-G, E-F, F-G, B-D, D-G, CD, D-E of all three thermoplastic denture base plates were measured and recorded with the help of a travelling microscope and were used for comparison with the measured and recorded readings of processed acrylic denture bases. The data obtained was analyzed by using the One Way Analysis of Variance., Results: The overall results of the in vitro study indicate that among all the PMMA bases cured by the two clamping systems and the different curing cycle, group A` was the most dimensionally stable, followed by control group A, then followed by B` and B was most unstable., Conclusion: The study concluded that the denture bases fabricated by the R.S Technique using the long curing cycle would produce the most dimensionally stable PMMA denture bases. How to cite the article: Babu MR, Rao CS, Ahmed ST, Bharat JS, Rao NV, Vinod V. A comparative evaluation of the dimensional accuracy of heat polymerised PMMA denture base cured by different curing cycles and clamped by R S technique and conventional method - An In-vitro study. J Int Oral Health 2014;6(2):68-75.

Neutrophil elastase (NE) is a major inflammatory mediator in cystic fibrosis (CF) that is a robust predictor of lung disease progression. NE directly causes airway injury via protease activity, and propagates persistent neutrophilic inflammation by up-regulation of neutrophil chemokine expression. Despite its key role in the pathogenesis of CF lung disease, there are currently no effective antiprotease therapies available to patients with CF. Although heparin is an effective antiprotease and anti-inflammatory agent, its anticoagulant activity prohibits its use in CF, due to risk of pulmonary hemorrhage. In this report, we demonstrate the efficacy of a 2-O, 3-O-desulfated heparin (ODSH), a modified heparin with minimal anticoagulant activity, to inhibit NE activity and to block NE-induced airway inflammation. Using an established murine model of intratracheal NE-induced airway inflammation, we tested the efficacy of intratracheal ODSH to block NE-generated neutrophil chemoattractants and NE-triggered airway neutrophilic inflammation. ODSH inhibited NE-induced keratinocyte-derived chemoattractant and high-mobility group box 1 release in bronchoalveolar lavage. ODSH also blocked NE-stimulated high-mobility group box 1 release from murine macrophages in vitro, and inhibited NE activity in functional assays consistent with prior reports of antiprotease activity. In summary, this report suggests that ODSH is a promising antiprotease and anti-inflammatory agent that may be useful as an airway therapy in CF.

Vibrio vulnificus, a halophilic pathogenic bacterium of marine environments, encounters changes in salinity in its natural habitat and in the food-processing environment. The comparative response of V. vulnificus to hyperosmotic and hypoosmotic stress in terms of gene expression was investigated. Genes belonging to the proU operon for transport of compatible solutes and compatible solute synthesis were significantly upregulated (3- to 4.7-fold) under hyperosmotic stress. Under hypoosmotic stress, upregulation of genes coding for mechanosensitive channels of small conductance (mscS) was not observed. In hyperosmotic conditions a 2.3-fold decrease in the expression of aqpZ was observed. A 2-fold induction in gyrA was observed in V. vulnificus cells on exposure to hyperosmotic stress. groEL genes, VVA1659 (1.6-fold), and VV3106 (1-fold) were induced in hypoosmotic condition. Results of this study indicate that to manage hyperosmotic stress, V. vulnificus accumulated osmoprotectants through uptake or through endogenous synthesis of compatible solutes. Expression of mscS may not be necessary for immediate protection in cells exposed to hyper- and hypo-osmotic stress. Comparative analysis of important osmotic-stress-related genes showed up- or down-regulation of 14 genes in hyperosmotic stress as compared with up- or down-regulation of only 7 genes in hypoosmotic stress, indicating that the cells respond asymmetrically to hyper- and hypo-osmotic stress.

Aim: The aim of this article is to present a simple method of communication between two oral health professionals so that the problem can be conveyed easily and treatment options obtained equally easily and quickly, using current electronic communication technologies., Background: Treatment of dental problems involves a thorough understanding of the underlying dental and medical conditions. The arena of dentistry being ever changing, with new specialties arising each year, it has become virtually impossible for an average dentist to keep track of all the treatment modalities available for various problems at a given time. It is the duty of a dentist, however, to treat his patients to the best of his ability. Professional ethics bind the other health professionals to render their opinion to the dentist so that the patient will ultimately get the best possible treatment. Method of communication is the only problem remaining in the path to achieving a total oral health care., Technique: DiaTreat is a unique method of clinical charting by which a dentist can incorporate all the ailments affecting his patient, and by withholding the patients name and address, can communicate with any of his colleagues for their opinion on the best treatment option for his patient., Conclusion: It is a new and innovative method of communication between a dentist and specialist. Even though it has some shortcomings of its own, on a wider range, the advantages far outweigh the drawbacks of the system. CLINICAL AND ACADEMIC SIGNIFICANCE: This can also be used by educational institutes for easy communication during interdisciplinary exchanges. Improvements need to be made yet to incorporate all the ailments known in dental discipline and make communication a comprehensive one.

Aim: This study is to evaluate the role of 1:1 v/v 30% trichloromethane and monomer solvent in enhancing the durability of bonding between cross-linked acrylic teeth and different heatcured denture bases with or without mechanical preparations made on ridge lap portion of the artificial teeth., Materials and Methods: Two high impact denture base resin materials (Trevalon HI, DeTrey, UK, and DPI Tuff, Mumbai) and one nonhigh impact denture base resin material (DPI Quick Set, Mumbai) were selected to form three groups. Each group contains 30 specimens prepared by five different methods. A mixture of 30% trichloromethane and monomer, mixed in the ratio of 1:1 and applied for 1 minute on the ridge lap area of experimental specimens of methods--B, C, D and E (Specimens of method--A being control group, where no alterations were made at the ridge lap portion of acrylic teeth) before curing. Hounsfield universal testing machine is employed to evaluate the comparative bond strengths., Results: No significant difference was seen in bond strengths between specimens of experimental methods in all groups. When each group was assessed separately method B specimens in group 1 (739.2 N), group 2 (758 N) and method D specimens in group 3 (729 N) showed highest mean bond strengths. Control group specimens showed the least bond strength (400-460 N) in all groups with more adhesive failures., Conclusion: Ridge lap portion of the specimens treated with chemical solvent as in method B showed increased bond strength in groups 1 and 2. Hence, this is a preferred method., Clinical Significance: Evaluation of effect of different chemical and mechanical preparations at the ridge lap areas of acrylic teeth before acrylization helps the clinician and technician to overcome the problem of debonding of teeth from denture bases and in turn provides better quality prosthesis to the patient.

Aim: The aim of this study is to evaluate the dimensional accuracy of heat polymerized acrylic resin denture base clamped by the conventional method and by new-press technique and cured by long curing cycle., Materials and Methods: In this study, a total of 60 standardized maxillary record bases were fabricated with seven reference points as follows: Point A: Incisive papilla, Point B and C: Canine region on either side Point E and G: Midpoint of tuberosities on either side Point F: Midpoint of the line joining the two tuberosities Point D: Midpoint between the line joining A and F., Group a: Ten maxillary record bases were fabricated by conventional clamping method and cured by long curing cycle. GROUP A': Ten maxillary record bases were fabricated by New Press or RS tension clamping method and cured by long curing cycle. The distances between the reference points, i.e. A-B, A-C, A-D, D-F, B-E, C-G, E-F, F-G, B-D, D-G, C-D, D-E of all three thermoplastic denture base plates were measured and recorded with the help of travelling microscope and were used for comparison with the measured and recorded readings of processed acrylic denture bases. The data obtained was analyzed by using the one-way analysis of variance and HSD Multiple Comparison Test., Results: The overall results of the study indicate that among all the denture bases cured by the two clamping systems and the long curing cycle, group A' were the most dimensionally stable, followed by control group A., Conclusion: The study concluded that the denture bases fabricated by the New Press method using the long curing cycle would produce the most dimensionally stable denture bases.

Mycobacterium tuberculosis-specific antibodies possess immunomodulatory effects during tuberculosis infection. Prior sensitization to environmental mycobacteria is known to suppress immune responses against BCG and M. tuberculosis. Mycobacteria-induced antibodies can influence events such as complement activation and phagocytosis during infectious process. In the present study role of anti-M. tuberculosis IgG (anti-M. tb IgG) antibody during interaction between M. tuberculosis and human macrophages mediated through complement has been examined in vitro. Anti-M. tb IgG antibody significantly enhanced complement activation by M. tuberculosis. Phagocytosis of M. tuberculosis by macrophages increased significantly in the presence of complement and/or antibody. Moreover, antibody enhanced phagocytosis in the presence of complement. Addition of antibody alone or in combination with complement also augmented intracellular viability of bacilli within macrophages. Results of this study showed that anti-mycobacterial antibody enhances complement activation and anti-M. tb IgG antibody probably modulates effects of complement during early stages of tuberculosis infection.

Aim: To evaluate and compare the shear bond strength of resilient liners with heat cure denture base resins in the presence or absence of saliva., Materials and Methods: Two commercially available heat polymerized acrylics and three commercially available denture liners were immersed in artificial saliva for 7 days and 14 days, respectively. A total of 180 (Acralyn-H, No.90 and Lucitone - 199, No.90) specimens were prepared. Total of 90 overlapping joint specimens were prepared, 45 of them using Acralyn H (AGroup) and rest 45 using Lucitone-199 (L-Group). The specimens were tested for flexural strength with a 3-point bending test on an Instron universal testing machine. The results were analyzed with a one-way analysis of variance (ANOVA)., Results: The mean difference in shear bond strength (SBS) at different time intervals was found to be statistically significant (p < 0.001). Lucitone-199 recorded a significantly higher mean SBS compared to Acralyn H (p < 0.001). Further, significant differences between GC and Densply, GC and Aswin liners, and between Dentsply and Aswin were noted (p < 0.001). Difference between baseline and 7 days time interval, as well as, between baseline and 14 days time interval with respect to the mean SBS of these materials were significant (p < 0.001). Also, the mean difference in SBS between 7 days time interval and 14 days time interval was statistically significant (p < 0.001). Among the three different liners, GC yielded a higher mean SBS compared to Aswin and Dentsply at all the three time intervals. The mean SBS recorded in Dentsply and Aswin was almost same at 14 days time interval, but at baseline and 7 days, it was higher in Aswin compared to Dentsply., Conclusion: Lucitone-199 recorded a higher mean SBS compared to Acralyn H. As the time interval increases, the mean SBS recorded in both the denture base materials decrease. Among the three different liners, GC yields a higher mean SBS compared to Aswin and Dentsply at all the three time intervals., Clinical Significance: The most common reason for failures of resilient linings in removable dentures is the separation of these linings from the denture base. Therefore, poor adhesive bond properties are one of the serious defects of the material in clinical practice.

Unlabelled: Arrangement of artificial teeth in a bilaterally symmetrical fashion with proper inclinations of teeth had been a challenging task for beginners. A variety of tools and guiding equipment have been developed to help students to learn teeth arrangement. Unfortunately, those tools were either costly or unsuitable for use with mean value articulators. This article attempts to introduce a simplified clinometer which can be attached to mean value articulator and can be used as a guide to arrange teeth in a bilaterally symmetrical manner by the undergraduates in both clinical and preclinical set-up., Clinical Significance: Training of the future dentists in sound esthetic principles in a preclinical environment, using this device, will increase the final clinical efficacy of their work., Aim: The aim of this article is to provide a simple but effective device to undergraduate students to help them learn teeth arrangement easily and systematically.

Circadian clocks have evolved as internal time keeping mechanisms that allow anticipation of daily environmental changes and organization of a daily program of physiological and behavioral rhythms. To better examine the mechanisms underlying circadian clocks in animals and to ask whether clock gene expression and function during development affected subsequent daily time keeping in the adult, we used the genetic tools available in Drosophila to conditionally manipulate the function of the CYCLE component of the positive regulator CLOCK/CYCLE (CLK/CYC) or its negative feedback inhibitor PERIOD (PER). Differential manipulation of clock function during development and in adulthood indicated that there is no developmental requirement for either a running clock mechanism or expression of per. However, conditional suppression of CLK/CYC activity either via per over-expression or cyc depletion during metamorphosis resulted in persistent arrhythmic behavior in the adult. Two distinct mechanisms were identified that may contribute to this developmental function of CLK/CYC and both involve the ventral lateral clock neurons (LN(v)s) that are crucial to circadian control of locomotor behavior: (1) selective depletion of cyc expression in the LN(v)s resulted in abnormal peptidergic small-LN(v) dorsal projections, and (2) PER expression rhythms in the adult LN(v)s appeared to be affected by developmental inhibition of CLK/CYC activity. Given the conservation of clock genes and circuits among animals, this study provides a rationale for investigating a possible similar developmental role of the homologous mammalian CLOCK/BMAL1 complex., Competing Interests: The authors have declared that no competing interests exist.

Wettability studies are of importance for electronic devices. Various methods are known to convert the hydrophobic substrates to hydrophilic substrates, but the studies on the relative dependence of wettability with varying concentrations of an aqueous system are meager. The wetting of different substrates with varying concentration of 1,4-dioxane in water is investigated and the results of concentration dependence of wetting are presented. The FTIR spectrum shows a blue shift of the OH peak--a feature typical of aqueous-1,4-dioxane systems. Concentration dependence of dielectric permittivity of this system also showed an anomaly., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: Rosacea is a common disfiguring skin disease of primarily Caucasians characterized by central erythema of the face, with telangiectatic blood vessels, papules and pustules, and can produce skin thickening, especially on the nose of men, creating rhinophyma. Rosacea can also produce dry, itchy eyes with irritation of the lids, keratitis and corneal scarring. The cause of rosacea has been proposed as over-production of the cationic cathelicidin peptide LL-37., Methodology/principal Findings: We tested a new class of non-anticoagulant sulfated anionic polysaccharides, semi-synthetic glycosaminoglycan ethers (SAGEs) on key elements of the pathogenic pathway leading to rosacea. SAGEs were anti-inflammatory at ng/ml, including inhibition of polymorphonuclear leukocyte (PMN) proteases, P-selectin, and interaction of the receptor for advanced glycation end-products (RAGE) with four representative ligands. SAGEs bound LL-37 and inhibited interleukin-8 production induced by LL-37 in cultured human keratinocytes. When mixed with LL-37 before injection, SAGEs prevented the erythema and PMN infiltration produced by direct intradermal injection of LL-37 into mouse skin. Topical application of a 1% (w/w) SAGE emollient to overlying injected skin also reduced erythema and PMN infiltration from intradermal LL-37., Conclusions: Anionic polysaccharides, exemplified by SAGEs, offer potential as novel mechanism-based therapies for rosacea and by extension other LL-37-mediated and RAGE-ligand driven skin diseases.

We explore the effects of nanoscale morphology of supporting solid substrates on alignment, defects, and director structures exhibited by thin films of triphenylamine-based discotic liquid crystals. Fluorescence confocal polarizing microscopy and intrinsic polarized fluorescence properties of studied molecules are used to visualize three-dimensional director fields in the liquid crystal films. We demonstrate that, by controlling surface anchoring on supporting or confining solid substrates such as those of carbon nanotube electrodes on glass plates, both uniform homeotropic and in-plane (edge-on) alignment and nonuniform structures with developable domains can be achieved for the same discotic liquid crystal material.

Recently, the topographic patterning of surfaces by lithography and nanoimprinting has emerged as a new and powerful tool for producing single structural domains of liquid crystals and other soft materials. Here the use of surface topography is extended to the organization of liquid crystals of bent-core molecules, soft materials that, on the one hand, exhibit a rich, exciting, and intensely studied array of novel phases, but that, on the other hand, have proved very difficult to align. Among the most notorious in this regard are the polarization splay modulated (B7) phases, in which the symmetry-required preference for ferroelectric polarization to be locally bouquet-like or "splayed" is expressed. Filling space with splay of a single sign requires defects and in the B7 splay is accommodated in the form of periodic splay stripes spaced by defects and coupled to smectic layer undulations. Upon cooling from the isotropic phase this structure grows via a first order transition in the form of an exotic array of twisted filaments and focal conic defects that are influenced very little by classic alignment methods. By contrast, growth under conditions of confinement in rectangular topographic channels is found to produce completely new growth morphology, generating highly ordered periodic layering patterns. The resulting macroscopic order will be of great use in further exploration of the physical properties of bent-core phases and offers a route for application of difficult-to-align soft materials as are encountered in organic electronic and optical applications.

Objective: To estimate the prevalence of malnutrition among free-living elderly in a rural population of south India., Design: Cross-sectional study. Nutritional status was assessed using the Mini Nutritional Assessment (MNA) questionnaire, which is an eighteen-item nutritional screening instrument used in the elderly., Setting: Kaniyambadi block, a rural development block in the state of Tamil Nadu, south India., Subjects: Community-dwelling elderly (aged 60 years and above)., Results: As evaluated by the MNA, 14 % of the 227 subjects were malnourished and 49 % were at risk of malnourishment. No significant difference was found between men and women. The majority of the elderly were living with their children, had no income and consumed three meals per day. Older age (P < 0.001), decreased food intake (P < 0.001) and consuming fewer meals (P < 0.001) were independently associated with lower MNA scores., Conclusions: More than 60 % of the subjects had low MNA scores (<23.5) indicating that deficient protein-energy intake is common among rural elderly of south India and requires more attention.

Ethnopharmacological Relevance: Kigelia pinnata DC is extensively used in Indian traditional medicine for several diseases including inflammatory and painful disorders., Aim of the Study: The aim of the present study is to investigate the possible anti-inflammatory and analgesic activities of methanolic extract of Kigelia pinnata flower (MKFL) to support the medicinal uses claimed by folklore practitioners., Materials and Methods: MKFL is evaluated for its anti-inflammatory activity in carrageenan-induced paw edema model in rats and analgesic activity in acetic acid-induced writhing, hot plate and formalin-induced paw licking models in mice., Results: MKFL exhibited a significant (P<0.01) anti-inflammatory and analgesic activities with the doses of 100, 200 and 400mg/kg b.w. in rats and mice respectively., Conclusions: The results of the experimental study thus strongly support the traditional use of this plant for inflammatory and pain disorders., (Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.)

While heparin has been used almost exclusively as a blood anticoagulant, important literature demonstrates that it also has broad anti-inflammatory activity. Herein, using low anti-coagulant 2-O,3-O-desulfated heparin (ODSH), we demonstrate that most of the anti-inflammatory pharmacology of heparin is unrelated to anticoagulant activity. ODSH has low affinity for anti-thrombin III, low anti-Xa, and anti-IIa anticoagulant activities and does not activate Hageman factor (factor XII). Unlike heparin, ODSH does not interact with heparin-platelet factor-4 antibodies present in patients with heparin-induced thrombocytopenia and even suppresses platelet activation in the presence of activating concentrations of heparin. Like heparin, ODSH inhibits complement activation, binding to the leukocyte adhesion molecule P-selectin, and the leukocyte cationic granular proteins azurocidin, human leukocyte elastase, and cathepsin G. In addition, ODSH and heparin disrupt Mac-1 (CD11b/CD18)-mediated leukocyte adhesion to the receptor for advanced glycation end products (RAGE) and inhibit ligation of RAGE by its many proinflammatory ligands, including the advanced glycation end-product carboxymethyl lysine-bovine serum albumin, the nuclear protein high mobility group box protein-1 (HMGB-1), and S100 calgranulins. In mice, ODSH is more effective than heparin in reducing selectin-mediated lung metastasis from melanoma and inhibits RAGE-mediated airway inflammation from intratracheal HMGB-1. In humans, 50% inhibitory concentrations of ODSH for these anti-inflammatory activities can be achieved in the blood without anticoagulation. These results demonstrate that the anticoagulant activity of heparin is distinct from its anti-inflammatory actions and indicate that 2-O and 3-O sulfate groups can be removed to reduce anticoagulant activity of heparin without impairing its anti-inflammatory pharmacology.

Heparin desulfated at the 2-O and 3-O positions (ODSH) decreases canine myocardial reperfusion injury. We hypothesized that this occurs from effects on ion channels rather than solely from anti-inflammatory activities, as previously proposed. We studied closed-chest pigs with balloon left anterior descending coronary artery occlusion (75-min) and reperfusion (3-h). ODSH effects on [Na(+)](i) (Na Green) and [Ca(2+)](i) (Fluo-3) were measured by flow cytometry in rabbit ventricular myocytes after 45-min of simulated ischemia [metabolic inhibition with 2 mM cyanide, 0 glucose, 37 degrees C, pacing at 0.5 Hz; i.e., pacing-metabolic inhibition (PMI)]. Na(+)/Ca(2+) exchange (NCX) activity and Na(+) channel function were assessed by voltage clamping. ODSH (15 mg/kg) 5 min before reperfusion significantly decreased myocardial necrosis, but neutrophil influx into reperfused myocardium was not consistently reduced. ODSH (100 microg/ml) reduced [Na(+)](i) and [Ca(2+)](i) during PMI. The NCX inhibitor KB-R7943 (10 microM) or the late Na(+) current (I(Na-L)) inhibitor ranolazine (10 microM) reduced [Ca(2+)](i) during PMI and prevented effects of ODSH on Ca(2+) loading. ODSH also reduced the increase in Na(+) loading in paced myocytes caused by 10 nM sea anemone toxin II, a selective activator of I(Na-L). ODSH directly stimulated NCX and reduced I(Na-L). These results suggest that in the intact heart ODSH reduces Na(+) influx during early reperfusion, when I(Na-L) is activated by a burst of reactive oxygen production. This reduces Na(+) overload and thus Ca(2+) influx via NCX. Stimulation of Ca(2+) extrusion via NCX later after reperfusion may also reduce myocyte Ca(2+) loading and decrease infarct size.