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Receptor for advanced glycation end products (RAGE), a member of the immunoglobulin family, interactions with its ligands trigger downstream signaling and induce an inflammatory response linked to diabetes, inflammation, carcinogenesis, cardiovascular disease, and a variety of other human disorders. The interaction of RAGE and S100A6 has been associated with a variety of malignancies. For the control of RAGE-related illnesses, there is a great demand for more specialized drug options. To identify the most effective target for combating human malignancies associated with RAGE-S100A6 complex, we conducted single and differential gene expression analyses of S100A6 and RAGE, comparing normal and malignant tissues. Further, a structure-based virtual screening was conducted using the ZINC15 database. The chosen compounds were then subjected to a molecular docking investigation on the RAGE active site region, recognized by the various cancer-related RAGE ligands. An optimized RAGE structure was screened against a library of drug-like molecules. The screening results suggested that three promising compounds were presented as the top acceptable drug-like molecules with a high binding affinity at the RAGE V-domain catalytic region. We depicted that these compounds may be potential RAGE inhibitors and could be used to produce a successful medication against human cancer and other RAGE-related diseases based on their various assorted parameters, binding energy, hydrogen bonding, ADMET characteristics, etc. MD simulation on a time scale of 50 ns was used to test the stability of the RAGE-inhibitor complexes. Therefore, targeting RAGE and its ligands using these drug-like molecules may be an effective therapeutic approach.

Iron deposition in the central nervous system (CNS) is one of the causes of neurodegenerative diseases. Human transferrin (hTf) acts as an iron carrier present in the blood plasma, preventing it from contributing to redox reactions. Plant compounds and their derivatives are frequently being used in preventing or delaying Alzheimer's disease (AD). Thymoquinone (TQ), a natural product has gained popularity because of its broad therapeutic applications. TQ is one of the significant phytoconstituent of Nigella sativa. The binding of TQ to hTf was determined by spectroscopic methods and isothermal titration calorimetry. We have observed that TQ strongly binds to hTf with a binding constant (K) of 0.22 × 10

This article examines the impact of domestic remittances on the labour supply of men and women in recipient households in rural India. Applying the instrumental variable approach to data from the National Sample Survey, estimates indicate that remittances have a negative effect on the labour force participation of left‐behind household members. They do not seem to affect participation in regular salaried work but cause a decline in participation in casual wage work and unpaid family work, and an increase in self‐employment, especially among female household members. Additionally, the receipt of remittances significantly increases women's participation in household duties outside the labour market.

Este articulo examina el impacto de las remesas de migrantes internos en la oferta de trabajo de hombres y mujeres de los hogares receptores en la India rural. Las estimaciones con variables instrumentales y datos de la National Sample Survey indican que el efecto es negativo. Las remesas no parecen afectar a la participacion en el trabajo asalariado regular, pero se asocian a una disminucion de la participacion en el trabajo asalariado ocasional y en el trabajo familiar no remunerado y a un aumento del empleo no subordinado, especialmente entre las mujeres del hogar. Ademas, las remesas aumentan significativamente la participacion femenina en las tareas domesticas.

Mixed-matrix membranes (MMMs) with combination of two distinct dimensional nanofillers (such as 1D-3D, 2D-3D, or 3D-3D, etc.) have drawn special attention for gas separation applications due to their concerted effects on gas permeation and mechanical properties. An amine-functionalized 1D multiwalled carbon nanotube (NH2 -MWCNT) with exceptional mechanical strength and rapid gas transport was crosslinked with an amine-functionalized 3D metal-organic framework (UiO-66-NH2 ) with high CO2 affinity in a Schiff base reaction. The resultant crosslinked mixed-dimensional nanostructure was used as a nanofiller in a polysulfone (PSf) polymer matrix to explore the underlying synergy between 1D and 3D nanostructures on the gas separation performance of MMMs. Cross-sectional scanning electron microscopy and mapping revealed the homogenous dispersion of UiO-66@MWCNT in the polymer matrix. The MMM containing 5.0 wt. % UiO-66@MWCNT demonstrated a superior permeability 8.3 Barrer as compared to the 4.2 Barrer of pure PSf membrane for CO2 . Moreover, the selectivity (CO2 /CH4 ) of this MMM was enhanced to 39.5 from the 28.0 observed for pure PSf under similar conditions of pressure and temperature.

Nanotechnology has transformed the world with its diverse applications, ranging from industrial developments to impacting our daily lives. It has multiple applications throughout financial sectors and enables the development of facilitating scientific endeavors with extensive commercial potentials. Nanomaterials, especially the ones which have shown biomedical and other health-related properties, have added new dimensions to the field of nanotechnology. Recently, the use of bioresources in nanotechnology has gained significant attention from the scientific community due to its 100 % eco-friendly features, availability, and low costs. In this context, jute offers a considerable potential. Globally, its plant produces the second most common natural cellulose fibers and a large amount of jute sticks as a byproduct. The main chemical compositions of jute fibers and sticks, which have a trace amount of ash content, are cellulose, hemicellulose, and lignin. This makes jute as an ideal source of pure nanocellulose, nano-lignin, and nanocarbon preparation. It has also been used as a source in the evolution of nanomaterials used in various applications. In addition, hemicellulose and lignin, which are extractable from jute fibers and sticks, could be utilized as a reductant/stabilizer for preparing other nanomaterials. This review highlights the status and prospects of jute in nanotechnology. Different research areas in which jute can be applied, such as in nanocellulose preparation, as scaffolds for other nanomaterials, catalysis, carbon preparation, life sciences, coatings, polymers, energy storage, drug delivery, fertilizer delivery, electrochemistry, reductant, and stabilizer for synthesizing other nanomaterials, petroleum industry, paper industry, polymeric nanocomposites, sensors, coatings, and electronics, have been summarized in detail. We hope that these prospects will serve as a precursor of jute-based nanotechnology research in the future.

Water oxidation is a bottleneck in artificial photosynthesis that impedes its practicality for solar energy conversion and utilization. It is highly desired to significantly improve the efficacy of the existing catalysts or to rationally design new catalysts with improved performance. We report a novel conjugated and sulfone containing polyimide as a metal-free photocatalyst synthesized via a two-step method: (i) synthesis of precursor poly(amic acid) (PAA) (ii) solvothermal synthesis of polyimide through thermal imidization. The synthesis of the polyimide photocatalyst was demonstrated by the amide linkage in the FTIR spectrum. The obtained photocatalyst was semicrystalline in nature and possessed sheet-like morphology as illustrated by the diffraction pattern and the electron micrographic images, respectively. The thermogravimetric analysis of the polyimide nanosheets validated a thermally stable structure. The DFT calculations were performed which showed a suitable HOMO band position, favorable for water oxidation. The photoelectrocatalytic (PEC) performance of the polyimide nanosheets evaluated by studying water oxidation reaction without any sacrificial agent under 1-SUN showed enhanced PEC performance and good stability towards water oxidation at 0 V versus SCE.

Resource depletion is a concern for the global economy; many think that available resources on the planet will not be able to cater to an ever‐growing population. Thus, economies are trying to become circular, leaving behind the linear tradition linear approach. In the circular economy (CE), physical resources and energy are made to loop back into the supply chain (SC) for a more extended period. Proper selection of suppliers is an essential criterion towards proper execution of the CE principle in SC. In this research, we have constructed a framework for evaluating the supplier concerning the CE implementation. Further, this research identifies the criterion and sub‐criterion, which are pertinent for evaluating the supplier in CE context. Fuzzy‐based ‘Criteria Importance Through Inter‐Criteria Correlation (CRITIC)’ method is justifiably applied to determine the aggregated weights of the criteria. Finally, ‘Technique for Order of Preference by Similarity to Ideal Solution (TOPSIS)’ method is used to determine the suppliers' ranking in the Indian automobile industry. Six criteria and 24 sub‐criteria are obtained as per recent literature and then inputs from experts. ‘Environment’ criterion came out as the most favourable criterion with a subjective weight of 0.230. The current research is one of the first such attempts to provide criteria for supplier selection in a CE environment. The developed framework would help organisations in implementing CE‐based supplier selection. The identified criteria and sub‐criteria would provide organisations with means to evaluate suppliers and help suppliers develop an effective and efficient CE based on the SC.

In the present work, optical, electrical, and photophysical properties of poly(3-hexylthiophen)/silver sulphide (P3HT/Ag2 S) nanocomposites thin films were investigated. New amorphous dispersion formula was used to fit the experimental ellipsometer data and it was observed that the both refractive index (n) and absorption index (k) increased for hybrid films compared with pure P3HT film. The photophysical properties of fabricated films were examined by recording the photoluminescence (PL) and time resolved fluorescence spectra. The PL quenching in hybrid films signalled the formation of a charge transfer complex between host (P3HT) and guest (Ag2 S). The fluorescence average life time was noted to drop to 94 ps for hybrid P3HT:Ag2 S 1:2 film compared with 126 ps for pristine P3HT. Finally, the electrical properties of fabricated films were measured using the Hall effect systems. The surface resistivity (ρ) of pure P3HT thin films was found to be 9.70 × 104 Ω.cm, which decreased slightly for Ag2 S/P3HT hybrid films.

Osteoarthritis (OA) is a chronic degenerative and musculoskeletal disorder. The toxicity associated with nonsteroidal antiinflammatory drugs (NSAIDs) limits its use in the management of OA. To ameliorate these toxicities, natural antioxidants can be used as substitutes for the management of OA. Therefore, this study is aimed to investigate the prophylactic mechanisms of Punica granatum L. peel (PGP) in collagenase-induced OA rat compared with indomethacin. OA was induced in female Sprague Dawley rats by intraarticular injection of collagenase type-II and treated with PGP (250 and 500 mg/kg body wt) and a positive control (PC) indomethacin (3 mg/kg body wt). The results demonstrated that PGP reduced the collagenase induced OA as compared with indomethacin treated group through reducing blood ALP (P < .001) and significantly (P < .001) inhibited cartilage erosion as indicated in histological slides with retention of collagen and proteoglycan content. Quantitative real-time PCR analysis revealed the considerable (P < .05) upregulation in the expression of COL-2 gene and downregulation of MMP-3 and COX-2 genes in the PGP treated group. The high phenolic content (633 ± 1.16 mg/GAE) and flavonoid content (420.3 ± 2.14 mg/RE) contribute to the strong antioxidant activity with IC50 value (320 ± 2.2 μg/mL) of DPPH free radical scavenging activity. These results need further validation in clinical studies and thus, PGP could be developed as a preventive drug treatment for OA.

The panchromatic light absorption and excellent charge carrier transport properties in organo lead halide perovskites allowed to achieve an unprecedented power conversion efficiency in excess of 25 % for thin film photovoltaics fabrication. To understand the underlying phenomena, various comprehensive set of optical and electrical techniques have been employed to investigate the charge carrier dynamics in such devices. In this perspective, we aim to summarize the electrical transport properties of perovskite thin films by using (i) impedance spectroscopy (IS), (ii) space charge limited current (SCLC), (iii) field-effect transistors (FETs) and (iv) time-of-flight (TOF) methods. We have deliberated various equivalent circuit used to model the perovskite solar cells by means of IS. The SCLC technique provide vital electrical parameters such as mobility, activation energy, traps density and distribution, carrier concentration, density of states, etc. The TOF technique measures mobility as a primary parameter while the FETs configuration provide a valuable insight into the in-plane charge transport in perovskites thin films. We believe that these notable understanding will provide insights into charge carrier dynamics in perovskite materials and devices.

The present study was aimed to explore the molecular and structural features of UDP-N-acetylglucosamine pyrophosphorylase of Bombyx mori (BmUAP), an essential enzyme for chitin synthesis in insects. The BmUAP cDNA sequence was cloned and expression profiles were monitored during the molting and feeding stages of silkworm larvae. The effect of 20-hydroxyecdysone (20E) on BmUAP expression, and on silkworm molting was studied, which revealed that 20E regulates its expression. Multiple sequence alignment of various pyrophosphorylases revealed that the residues N223, G290, N327, and K407 of human UAP (PDB ID: 1JV1) were found to be highly conserved in BmUAP and all other eukaryotic UAPs considered for the study. Phylogenetic analysis inferred that the UAPs possess discrete variations in primary structure among different insect Orders while sharing good identity between species of the Order. The structure of BmUAP was predicted and its interactions with uridine triphosphate, N-acetylglucosamine-1-phosphate, and UDP-N-acetylglucosamine were analyzed. Virtual screening with a library of natural compounds resulted in five potential hits with good binding affinities. On further analysis, these five hits were found to be mimicking substrate and product, in inducing conformational changes in the active site. This work provides crucial information on molecular interactions and structural dynamics of insect UAPs.

Exon 2 of MHC class II gene codes for the first domain of the molecule that forms the peptide-binding groove and its polymorphism partly explains functional MHC diversity. A 850 bp DQA1 gene fragment spanning from intron I to exon III was typed by sequencing of 40 Tharparkar cattle of various agro-climatic zones of northern India along with 10 Tharparkar crossbreds. On analysis of nucleotide sequences, a total of 30 polymorphic sites (1 insertion and 29 SNPs) were identified in 14 MHC alleles leading to amino acid changes in 5 places in 249 bp (exon 2). Five new BoLa DQA1 alleles were identified and reported. The within group mean distance was highest in Tharparkar herd of Bikaner (0.045) and lowest (0.020) in that of Surathgarh (breeding tract) whereas, between groups mean distance was highest in Bikaner Tharparkar-Suratgarh Tharparkar pair. There was excess of nonsynonymous over synonymous nucleotide substitutions in the present study. The effects of these substitutions were predicted using I-Mutant and Panther online resources. The mean ratio of dN/dS was found to be >1.0 at 12 codons with two mutation hotspots at 13th codon (P = 0.002) and 64th codon (P = 0.01). The phylo-geographic analysis revealed that alleles 5, 7 and 13 formed a different cluster with alleles 7 and 13 grouped by the most frequent allele (BoLa-DQA*1401).

Inosine pranobex (IP), an immunomodulatory agent, is used in the treatment of various viral infections. The results of a phase 3 randomized controlled trial are reported, evaluating the efficacy and safety of IP in the treatment of mild to moderate COVID-19. It includes 416 symptomatic patients with confirmed SARS-CoV-2 infection. In addition to a defined standard of care, patients randomly (1:1) receive either IP 500 mg tablet (IP group) or a matching placebo (placebo group) at 50 mg kg

We have developed a new series of simple biaryl piperidine derivatives (11-19) based on biaryl naphthylisoquinoline alkaloid Ealamine-A. The target compounds were synthesized, analyzed by spectral data, and evaluated for antileishmanial activity against Leishmania donovani strain Ag83 by MTT assay. The compounds have shown the best to moderate antileishmanial activity. The 5'-fluoro-2'-methoxyphenyl derivative 14 and 3',5'-difluorophenyl derivative 16 have inhibited the promastigotes by 86 % and 85 % after 24 h and 92 % and 91 % after 48 h incubation, respectively, at 400 μM concentration. The % inhibition was lower with the lowering of the concentration and increased with the incubation time. Compounds 12, 15, and 18 have solubility issues and proved to be less active than the rest of the compounds. Molecular docking studies were performed on selective active compounds and the results indicate that these compounds may act by binding to the Leishmanolysin and the docking scores are in good correlation with the antileishmanial activity. These results provide an initial insight into the design of new therapeutics for neglected tropical diseases.

Advanced glycation end products (AGEs) are directly related to third aging-associated diseases, such as cardiovascular diseases, arteriosclerosis, and neurodegeneration. Likewise, these irreversible and nonenzymatic products have been reported to be involved in the progression of malignant cancers. In general, aging-associated diseases and the initiation of cancer have been subjects of interest for several years. Few studies on the role of AGEs in cancer have been performed on cell lines. Moreover, past investigations in the field of glycation biology still lack the knowledge of in vivo and in vitro approaches for cancer cells. Accordingly, we aimed to focus on and establish a link between cancer and glycation with respect to all the possible AGEs. In our study, the levels of carboxymethyllysine (CML) increased by 50.94% in an animal model of glycation, whereas in an animal model of cancer, the contents of CML increased by 45.94% compared with their negative controls. Similarly, fluorescent AGEs were also examined and were found to be increased by 65.3% and 58.63% in the animal models of glycation and cancer, respectively, compared with the control subjects. The protein carbonyl contents were also found to be enhanced in the animal models of glycation and cancer. In our study, the levels of reactive oxygen species were also found to be significantly increased in the in vitro model of cancer cells as compared with the controls. Such an initial breakthrough indicated that AGEs were present in the serum of the animal models of cancer and glycation.

WOS: 000412877000020, Crop wild relatives are a reservoir of phenotypic variation not present in the germplasm of cultivated species and thus have great potential for crop improvement. However, issues of genetic compatibility often interfere with effective utilization of crop wild relative taxa. Among chickpea (Cicer arietinum L.) crop wild relatives, Cicer echinospermum P.H. Davis is the sole species in the secondary genepool, being partially compatible with the primary genepool that is composed of the cultigen and its progenitor wild species Cicer reticulatum Ladizinksy. We report results from genetic studies among interspecific hybrids between cultivated chickpea and accessions from six recently identified wild C. echinospermum sites in southeastern Turkey, encompassing the known genetic diversity of the secondary genepool. Our studies indicate that both hybrid sterility and hybrid breakdown occur and are associated with distinct subgroups of C. echinospermum. Analysis of early-generation progenies suggests that both hybrid sterility and hybrid breakdown are conditioned by one to few genetic loci. These results clarify ambiguity in the nature of the hybridization barriers of reduced fertility in interspecific crossing of cultivated chickpea with C. echinospermum and should foster a more systematic and wider use of C. echinospermum for base broadening of cultivated chickpea., US National Science Foundation Plant Genome ProgramNational Science Foundation (NSF) [NSF-PGRP 1339346]; Agriculture Development Fund of the Saskatchewan Ministry of Agriculture; Saskatchewan Pulse Growers; Western Grains Research Foundation; United States Agency for International Development under the Feed the Future ProgramUnited States Agency for International Development (USAID) [AID-OAA-A-14-00008], We thank Dr. T.H. Noel Ellis for helpful comments on an earlier draft of this manuscript. This research was supported by grants from US National Science Foundation Plant Genome Program NSF-PGRP 1339346 to D.R. Cook, E.J.B. von Wettberg, and R.V. Penmetsa; by a cooperative agreement from the United States Agency for International Development under the Feed the Future Program AID-OAA-A-14-00008 to D.R. Cook, E.J.B. von Wettberg, A. Kahraman, and R.V Penmetsa; and by grants to B. Tar'an from the Agriculture Development Fund of the Saskatchewan Ministry of Agriculture, The Saskatchewan Pulse Growers, and The Western Grains Research Foundation.

A tricomponent system, constituting monomer (methyl methacrylate, MMA), higher oxidation state transition-metal catalyst (FeBr3) and a ligand (triphenylphosphine, PPh3), MMA/FeBr3/PPh3 system without external initiator (alkyl halide) has been studied extensively with different spectroscopic analyses. To figure out the mechanism, a series of explicit model reactions were conducted with a molar ratio of [MMA]0/[FeBr3]0/[PPh3]0 = 200/1/n (n = 0.1–3.0) at 80 °C, and the corresponding polymerization behaviors were investigated. Combined with theoretical deduction and spectroscopic evidences, the composition of the in-situ generated initiators was gradually confirmed, which were redox products of FeBr3 and PPh3. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017

In this study, the rheological behavior of polyacrylamide solutions in the absence and presence of cationic Gemini surfactants (16-s-16, s = 5, 6) and their monomeric counterpart, cetyltrimethylammonium bromide, at different temperatures has been studied in the light of its application field by rheometry. The polyacrylamide solution shows the shear thinning behavior at a very low shear rate in the absence and presence of surfactants, and the Ostwald de model was used to describe the pseudoplastic behavior of polyacrylamide solution. The viscosity of polyacrylamide solution increases with the addition of surfactants, and the increase in viscosity is quite significant with Gemini surfactant as compared with their monomeric counterpart cetyltrimethylammonium bromide, indicating stronger interaction of polyacrylamide with Geminis. Further, transmission electron microscope results support the viscosity data. The results obtained are quite interesting and could be of prolific use for selection of polymer–surfactant mixtures and surfactants for use in enhance oil recovery. © 2017 Curtin University of Technology and John Wiley & Sons, Ltd.

Copper oxide nanomaterials were synthesized by a facile sustainable biological method using two plant species (Zanthoxylum armatum DC. and Berberis lycium Royle). The formation of materials was confirmed by FT-IR, ATR, UV-visible, XRD, TEM, SEM, EDX, TGA and PL. The antibacterial activity was evaluated by agar well diffusion method to ascertain the efficacy of plant species extract and extract derived copper oxide nanomaterials against six Gram-positive bacteria namely Staphylococcus aureus, Streptococcus mutans, Streptococcus pyogenes, Corynebacterium diphtheriae, Corynebacterium xerosis, Bacillus cereus and four Gram-negative bacteria such as Klebsiella pneumonia, Escherichia coli, Pseudomonas aeruginosa and Proteus vulgaris against the standard drug, Ciprofloxacin for Gram-positive and Gentamicin for Gram-negative bacteria, respectively. In both cases, copper oxide nanomaterials were found to be sensitive in all the bacterial species. Sensitivity of copper oxide nanomaterials shows an be higher as compared to plant species extract against different bacteria. Scavenging activity of plant extracts along with nanomaterials have been accessed using previously reported protocols employing ascorbic acid as standard. Scavenging activity of copper oxide nanomaterials shows an increase with increase in concentration. The biological activity (bactericidal and scavenging efficiency) of plant derived copper oxide nanomaterials revealed that these materials can be used as potent antimicrobial agent and DPPH scavengers in industrial as well as pharmacological fields.

α-Crystallin is a member of small heat shock proteins and is believed to play an exceptional role in the stability of eye lens proteins. The disruption or denaturation of the protein arrangement or solubility of the crystallin proteins can lead to vision problems including cataract. In the present study, we have examined the effect of chemical denaturants urea and guanidine hydrochloride (GdnHCl) on α-crystallin aggregation, with special emphasis on protein conformational changes, unfolding, and amyloid fibril formation. GdnHCl (4 M) induced a 16 nm red shift in the intrinsic fluorescence of α-crystallin, compared with 4 nm shift by 8 M urea suggesting a major change in α-crystallin structure. Circular dichroism analysis showed marked increase in the ellipticity of α-crystallin at 216 nm, suggesting gain in β-sheet structure in the presence of GdnHCl (0.5-1 M) followed by unfolding at higher concentration (2-6 M). However, only minor changes in the secondary structure of α-crystallin were observed in the presence of urea. Moreover, 8-anilinonaphthalene-1-sulfonic acid fluorescence measurement in the presence of GdnHCl and urea showed changes in the hydrophobicity of α-crystallin. Amyloid studies using thioflavin T fluorescence and congo red absorbance showed that GdnHCl induced amyloid formation in α-crystallin, whereas urea induced aggregation in this protein. Electron microscopy studies further confirmed amyloid formation of α-crystallin in the presence of GdnHCl, whereas only aggregate-like structures were observed in α-crystallin treated with urea. Our results suggest that α-crystallin is susceptible to unfolding in the presence of chaotropic agents like urea and GdnHCl. The destabilized protein has increased likelihood to fibrillate. Copyright © 2016 John Wiley & Sons, Ltd.

Interface engineering has become one of the facile and effective approach to improve solar cells performance, its long-term stability and retard unwanted side reaction. We have developed three passivating agents which can functionalize the surface and induce hydrophobicity by employing substituted thiazolium iodide (TMI) for perovskite solar cells fabrication. The role of TMI interfacial layers on microstructure and electro-optical properties was assessed for structural as well as transient absorption (TA) measurements. TMI treatment resulted into VOC and FF enhancement by reducing possible recombination paths at perovskite/HTM interface and by reducing the shallow as well as deep traps. These in turn allowed to achieve higher performance as compared to the pristine surface. Additionally, TMI passivated perovskite layer reduces considerably CH3NH3+ thermal diffusion and degradation induced by humidity. The un-encapsulated perovskite solar cells employing TMI exhibited a remarkable stability under moisture levels (~50% RH) retaining ~95% of initial PCE after 800 h of fabrication, paving potential scalable endeavour.

Parkinson’s disease and schizophrenia are disease end points of dopaminergic deficit and hyperactivity, respectively in the mid brain. Accordingly, current pharmacological interventions aim to rest...

Cathepsin K (CK), a lysosomal cysteine protease, is highly expressed in mature osteoclasts and degrades type 1 collagen. Odanacatib (ODN) is a selective and reversible CK inhibitor that inhibits bone loss in preclinical and clinical studies. Although an antiresorptive, ODN does not suppress bone formation, which led us to hypothesize that ODN may display restorative effect on the osteopenic bones. In a curative study, skeletally mature New Zealand rabbits were ovarectomized (OVX) and after induction of bone loss were given a steady-state exposure of ODN (9 mM/d) for 14 weeks. Sham-operated and OVX rabbits treated with alendronate (ALD), 17b-estradiol (E2), or parathyroid hormone (PTH) served as various controls. Efficacy was evaluated by assessing bone mineral density (BMD), bone microarchitecture (using micro-computed tomography), fluorescent labeling of bone, and biomechanical strength. Skeletal Ca/P ratio was measured by scanning electron microscopy (SEM) with X-ray microanalysis, crystallinity by X-ray diffraction, and bone mineral density distribution (tissue mineralization) by backscattered SEM. Between the sham and ODN-treated osteopenic groups, lumbar and femur metaphyseal BMD, Ca/P ratio, trabecular microstructure and geometric indices, vertebral compressive strength, trabecular lining cells, cortical parameters (femoral area and thickness and periosteal deposition), and serum P1NP were largely comparable. Skeletal improvements in ALD-treated or E2-treated groups fell significantly short of the sham/ODN/PTH group. However, the ODN group displayed reduced ductility and enhanced brittleness of central femur, which might have been contributed by higher crytallinity and tissue mineralization. Rabbit bone marrow stromal cells expressed CK and when treated with ODN displayed increased formation of mineralized nodules and decreased apoptosis in serum-deficient medium compared with control. In vivo, ODN did not suppress remodeling but inhibited osteoclast activity more than ALD. Taken together, we show that ODN reverses BMD, skeletal architecture, and compressive strength in osteopenic rabbits; however, it increases crystallinity and tissue mineralization, thus leading to increased cortical bone brittleness.

α-Crystallin, a member of small heat shock proteins, is the major structural protein within the eye lens and is believed to play an exceptional role in the stability of lens proteins and its transparency. In the current manuscript, we have investigated the effect of an organic solvent, trifluoroethanol (TFE), on the structure and function of α-crystallin isolated from camel eye lens. Incubation of this protein with TFE changed the secondary and tertiary structures, which resulted in the aggregation of α-crystallin as evidenced by intrinsic fluorescence, Rayleigh's scattering, Thioflavin T assay, and circular dichroism spectroscopic studies. The treatment with different concentrations of TFE led to increased exposure of hydrophobic domains of α-crystallin, which was observed by 8-anilino 1-napthalene sulfonic acid extrinsic fluorescence assay. These results clearly indicate that TFE induced significant changes in the secondary and tertiary structures of α-crystallin, leading to aggregation and amyloid formation. Furthermore, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay established the cytotoxicity of the aggregated α-crystallin towards HepG2 cell lines through reactive oxygen species production. In conclusion, α-crystallin protein was found to be susceptible to conformational changes by TFE, suggesting that α-crystallin, although basically acting like a heat shock protein and functionally displaying chaperone-like activity, might capitulate to change in lens environment induced by diseased conditions or age-related changes, resulting in cataract formation.

The present paper describes the chemical oxidative polymerization of pyrrole and methyl anthranilate, Ppy-MA, in different molar ratios in high yields. The polymerization takes place in the presence of H2O2 and FeSO4. Subsequently, electrically conducting nanocomposites Ppy-MA/TiO2 were obtained by in situ chemical oxidative polymerization using TiO2 nanoparticles in different molar ratios. The structure and morphology of black powdered copolymers, Ppy-MA, and their nanocomposites, Ppy-MA/TiO2, were ascertained using Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy, transmission electron microscopy, X-ray differential, thermogravimetric analysis, and differential thermal analysis. These studies have shown that the nanocomposites, Ppy-MA/TiO2, are thermally more stable, good electrical conductors as compared with their copolymers Ppy-MA. The copolymers Ppy-MA prepared from different monomer ratios and its nanocomposites Ppy-MA/TiO2 have been screened for their possible in vitro antibacterial activity against Staphylococcus aureus (ATCC 29213), Streptococcus mutans (ATCC 25175), Streptococcus pyogenes (MTCC 435), Staphylococcus epidermidis (MTCC 435), Bacillus cereus (MTCC 430), Corynebacterium xerosis (ATCC 373), Acetobacter bovis (Clinical isolate), Escherichia coli (ATCC 25922), Klebsiella pneumoniae (MTCC 109), Proteus vulgaris (MTCC 426), and Pseudomonas aeruginosa (MTCC 424) using ciprofloxacin and gentamicin as standard drugs. Moreover, the anthelmintic activities of copolymers Ppy-MA and its nanocomposites Ppy-MA/TiO2 have also been estimated against the standard drug, albendazole. Copyright © 2015 John Wiley & Sons, Ltd.

Objectives This report highlights phytoconstituents present in Cissus quadrangularis (CQ) extract and examines biphasic (proliferative and anti-proliferative) effects of its extract on bone cell proliferation, differentiation, mineralization, ROS generation, cell cycle progression and Runx2 gene expression in primary rat osteoblasts. Materials and methods Phytoconstituents were identified using gas chromatography–mass spectroscopy (GC-MS). Osteoblasts were exposed to different concentrations (10–100 μg/ml) of CQ extract and cell proliferation and cell differentiation were investigated at different periods of time. Subsequently, intracellular ROS intensity, apoptosis and matrix mineralization of osteoblasts were evaluated. We performed flow cytometry for DNA content and real-time PCR for Runx2 gene expression analysis. Results CQ extract's approximately 40 bioactive compounds of fatty acids, hydrocarbons, vitamins and steroidal derivatives were identified. Osteoblasts exposed to varying concentrations of extract exhibited biphasic variation in cell proliferation and differentiation as a function of dose and time. Moreover, lower concentrations (10–50 μg/ml) of extract slightly reduced ROS intensity, although they enhanced matrix mineralization, DNA content in S phase of the cell cycle, and levels of Runx2 expression. However, higher concentrations (75–100 μg/ml) considerably induced the ROS intensity and nuclear condensation in osteoblasts, while it reduced mineralization level, proportion of cells in S phase and Runx2 level of the osteogenic gene. Conclusions These findings suggest that CQ extract revealed concentration-dependent biphasic effects, which would contribute notably to future assessment of pre-clinical efficacy and safety studies.

Because of the potential association between periodontal disease and inflammation, the purpose of the present study is to examine the level of Toll-like receptor 4 (TLR-4), interleukin-18 (IL-18), and uric acid as markers of the inflammatory host response in the plasma and saliva of healthy individuals and patients with periodontitis. In addition, routine biochemical parameters such as fasting glucose, insulin, total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, alanine transaminase (ALT), and aspartate transaminase (AST) were measured. The authors also wanted to check whether patients with chronic periodontitis (CP) exhibit different modulations in salivary and/or plasma concentrations of these parameters compared with clinically healthy individuals.Saliva and plasma samples were collected from 40 patients with CP and 20 healthy individuals. TLR-4 and IL-18 measurements were done using commercially available enzyme-linked immunosorbent assay kits. Total, HDL, and LDL cholesterol; triglycerides; fasting glucose; AST; and ALT levels were analyzed on a biochemistry analysis system using specific kits. Non-parametric tests were used for certain parameters in the statistical analyses because the data did not follow Gaussian distribution.Significant differences were observed in plasma and salivary TLR-4 and IL-18 levels, along with clinical measurements such as plaque index and probing depth, in patients with CP (P0.001). The plasma level of TLR-4 was found to be increased from 0.99 to 3.28 ng/mL in patients with CP. Salivary TLR-4 levels also showed a slightly higher increase in the diseased state (12.44 to 29.97 ng/mL). A significant increase of ≈ 46% was recorded in the plasma IL-18 level. However, salivary IL-18 levels rose up to5-fold in the patients with CP compared with healthy individuals. The level of plasma uric acid was found to be highly significantly increased compared with control individuals. HDL cholesterol and triglyceride also showed significant differences (P0.02 and P0.03, respectively). Plasma glucose, total cholesterol, LDL cholesterol, and insulin levels did not show any significant difference. There was only a slight increase in plasma AST and ALT levels between diseased and healthy states (22.55 versus 25.50 IU/L and 12.35 versus 15.95 IU/L, respectively). However, salivary AST and ALT levels showed a ≈ 6-fold rise in the patients with CP compared with the healthy individuals. Cross-correlation analysis in the periodontitis disease group showed a significant association of plasma AST, salivary AST, and salivary ALT with uric acid level.Based on this study, the authors believe that TLR-4, IL-18, and uric acid could have a role in the inflammatory pathology of periodontitis. These parameters are suggested to be useful in the prognosis and diagnosis of CP. However, the mechanistic association of these parameters with inflammatory pathology of patients with periodontitis needs to be further elucidated in a higher number of samples.