A comprehensive study of eco-friendly natural pigment and its applications

Actinomycetes, a large group of filamentous bacteria account for 70–80% of secondary metabolites available commercially. The present investigation was undertaken with an aim to identify and characterize pigment from actinomycetes. Actinomycetes were isolated from rhizosphere soil samples collected from different regions of Madhya Pradesh state. Out of 85 actinomycetes, only 5 actinomycetes showed pigment production and based on diffusible pigment production ability one actinomycete ARITM02 was selected. The extraction of pigment was done by solvent extraction method using methanol and purified by TLC and column chromatography. The pigment was characterized by UV–Vis spectroscopy which showed the lamda maximum of 277.44. FTIR spectroscopy suggested various functional groups like amino group, amide group, hydroxide, benzene and lactone group. The Mass spectroscopy and NMR spectroscopy showed that the molecular mass of pigment is 621.7 and molecular formula is C34H43N3O8. The pigment was also tested for Antimicrobial activity against broad spectrum human pathogens, antioxidant test and toxicity test for safe use as a natural colorant in cosmetic, food, pharmaceutical and textile industries. The conclusion of study suggested that this novel pigment could be a versatile natural, safe and multipurpose.     

Recent advances in synthesis and surface modification of lanthanide-doped upconversion nanoparticles for biomedical applications

Lanthanide (Ln)-doped upconversion nanoparticles (UCNPs) with appropriate surface modification can be used for a wide range of biomedical applications such as bio-detection, cancer therapy, bio-labeling, fluorescence imaging, magnetic resonance imaging and drug delivery. The upconversion phenomenon exhibited by Ln-doped UCNPs renders them tremendous advantages in biological applications over other types of fluorescent materials (e.g., organic dyes, fluorescent proteins, gold nanoparticles, quantum dots, and luminescent transition metal complexes) for: (i) enhanced tissue penetration depths achieved by near-infrared (NIR) excitation; (ii) improved stability against photobleaching, photoblinking and photochemical degradation; (iii) non-photodamaging to DNA/RNA due to lower excitation light energy; (iv) lower cytotoxicity; and (v) higher detection sensitivity. Ln-doped UCNPs are therefore attracting increasing attentions in recent years. In this review, we present recent advances in the synthesis of Ln-doped UCNPs and their surface modification, as well as their emerging applications in biomedicine. The future prospects of Ln-doped UCNPs for biomedical applications are also discussed.     

Monoclonal anti-androgen receptor antibodies: Production,characterization, and potential diagnostic applications

Several monoclonal antibodies (mAbs) and novel mAb-based assays for the androgen receptors (AR) have been developed. Large amounts of the recombinant human AR protein produced by a baculovirus expression system were used as an antigen to produce mAbs. Twenty-nine AR-specific mAbs were first confirmed by Western blot analysis and were then characterized for their immunoglobulin isotypes, epitopes, and epitope localization in AR. Novel assays using flow cytometry and sandwich enzyme-linked immunosorbent assays (ELISA) were established to detect AR-expressing cells and to quantify soluble AR protein, respectively. Using immunostaining, we identified several anti-AR mAbs exclusively recognizing AR within the nuclei of the prostate cancer cell line LNCaP and of prostate tissues in both frozen and paraffin-embedded sections, whereas other mAbs could detect AR in both nuclear and cytoplasmic compartments. Interestingly, certain mAbs, such as G122-25 and G122-77, could distinguish the androgen-bound AR from the unoccupied AR. In sum, many purified AR protein and anti-AR mAbs, together with the assays developed, could be powerful tools for the study of functional AR and for the diagnosis of prostatic cancers.     

Metallic nanoparticles: microbial synthesis and unique properties for biotechnological applications,bioavailability and biotransformation

The impact of nanotechnology in all areas of science and technology is evident. The expanding availability of a variety of nanostructures with properties in the nanometer size range has sparked widespread interest in their use in biotechnological systems, including the field of environmental remediation. Nanomaterials can be used as catalysts, adsorbents, membranes, water disinfectants and additives to increase catalytic activity and capability due to their high specific surface areas and nanosize effects. Thus, nanomaterials appear promising for new effective environmental technologies. Definitely, nanotechnology applications for site remediation and wastewater treatment are currently in research and development stages, and new innovations are underway. The synthesis of metallic nanoparticles has been intensively developed not only due to its fundamental scientific interest but also for many technological applications. The use of microorganisms in the synthesis of nanoparticles is a relatively new eco-friendly and promising area of research with considerable potential for expansion. On the other hand, chemical synthesis occurs generally under extreme conditions (e.g. pH, temperature) and also chemicals used may have associated environmental and human health impacts. This review is an overview of current research worldwide on the use of microorganisms during the biosynthesis of metallic nanoparticles and their unique properties that make them good candidates for many applications, including in biotechnology.     

A physico-chemical and biological study of novel chitosan-chloroquinoline derivative for biomedical applications

This paper describes an elegant cross-linking technique for the preparation of chitosan-chloroquinoline derivative by using a greener technique. Chitosan solution in aqueous acetic acid was treated with 2-chloroquinoline-3-carbaldehyde solution to form hydrogel; the resulting hydrogel was subjected to solvent exchange. Combining the results of FTIR and XRD confirmed that 2-chloroquinoline-3-carbaldehyde have been reacted to chitosan. The morphology of the derivative was investigated by X-ray diffraction (XRD) and scanning electron microscopy (SEM). The thermal stability of the derivative was examined by thermogravimetric analysis (TGA). The photoluminescence (PL) spectra of chitosan-chloroquinoline derivative show red-shifted emission maximum. The microbiological screening has demonstrated the antimicrobial activity of the derivative against bacteria viz. Staphylococcus aureus, Escherichia coli and Candida albicans. The obtained results showed that the chitosan-chloroquinoline derivative might be a promising candidate for novel antimicrobial agents for biomedical applications.     

Titanium dioxide nanomaterial doped with trivalent lanthanide ions of Tb, Eu and Sm: Preparation, characterization and potential applications

Mesoporous Ln(III)-TiO₂ (Ln = Tb, Eu, Sm) nanomaterials composites have been successfully synthesized by using sol-gel technique.XRD pattern, FT-IR, Raman spectra, and SEM were used to characterize the Ln(III)-TiO₂ nanomaterials. The prepared lanthanide doped TiO₂ nanomaterials have anatase phase and exhibit Ti-O-Ln bond. The absorption spectra of all prepared samples reflect the increasing photoresponse of doped samples to visible light over pure TiO₂. Surface area is remarkably increased due to lanthanide ion-doping.Two newly prepared Ln(III)-TiO₂ (Ln = Eu, Sm) luminescent nanomaterials exhibit enhanced pure red or orange light emission due to energy transfer from host TiO₂ to guest Eu(III) or Sm(III), respectively.In addition, the commercially available textile dye Remazol Red RB-133 degradation was used as a probe reaction to determine the efficiency of the Ln(III)-TiO₂ photocatalysts. The Ln(III) doping brought about remarkable improvement in the photoactivity over pure TiO₂.     

Synthesis, characterization, and aqueous chemistry of cytotoxic Au(III) polypyridyl complexes

This work reports the synthesis, characterization, and aqueous chemistry of a series of cytotoxic [Au(polypyridyl)Cl₂]PF₆ complexes {(where polypyridyl = dipyrido[3,2-f:2′,3′-h] quinoxaline (DPQ), dipyrido[3,2-a:2′,3′-c] phenazine (DPPZ) and dipyrido[3,2-a:2′,3′-c](6,7,8,9-tetrahydro) phenazine (DPQC))}. The crystal structure of [Au(DPQ)Cl₂]PF₆ was determined as example of the series and exhibits the anticipated square planar geometry common for d⁸ coordination complexes. The crystals of the complex belong to the space group P2₁/n with a = 7.624(2) Å, b = 18.274(5) Å, c = 14.411(14) Å, β = 98.03(3)°, and Z = 4. In ¹H NMR studies of these compounds in the presence of aqueous buffer, all four complexes rapidly converted to the dihydroxy species [Au(polypyridyl)(OH)₂] in a stepwise fashion. However, the [Au(polypyridyl)]³⁺ fragment believed to impart cytotoxicity in human ovarian cancer cell lines (A2780) remained intact and appeared stable for days. It was also noted that these Au(III) complexes were readily reduced in the presence of the common biological reducing agents, reduced glutathione and sodium ascorbate. How solution and redox stability may affect the biological activity of these novel Au(III) complexes is discussed.     

Development of silver-containing austenite antibacterial stainless steels for biomedical applications Part I: microstructure characteristics,mechanical properties and antibacterial mechanisms

The as-quenched (AQ) microstructure of the Ag-containing alloys was found to be essentially a mixture of austenite (γ) and Ag phases. The Ag phase precipitates had a face-centered-cubic structure and lattice parameter a = 4.09 Å. When the alloy contained Ag ≥0.2 wt%, the mechanical properties were slightly enhanced because of the precipitate strengthening by the Ag phase precipitates. Moreover, the Ag-containing alloys exhibited ductile fracture after tensile testing. The results of an antibacterial test revealed that the Ag phase precipitates play a key role in the antibacterial mechanism of Ag-containing alloys: Ag⁺ ions released from the Ag phase precipitates can kill bacteria. It is suggested that as AISI 316L alloy has an Ag content ≥0.2 wt%, it will have excellent antibacterial properties against both Staphylococcus aureus and Escherichia coli, with an antibacterial rate of nearly 100%.     

Adjuvant treatment of breast cancer: A pilot immunochemotherapy study with CMF, interleukin-2 and interferon alpha

Immune responses, including natural immunity (NI), potentiate the antitumor effects of chemotherapy. Since interferons and interleukin-2 (IL-2) augment NI, a pilot study was conducted to assess the tolerability and the effects on host immunity of adjuvant chemotherapy associated with IL-2 + interferon alpha (IFN) in breast cancer patients after surgery. Ten patients underwent alternating 28-day cycles of chemoimmunotherapy [cyclophosphamide + methotrexate + 5-fluorouracil (CMF, days 1, 8) + IL-2 (days 15–19) + IFN (day 22)] and chemotherapy alone (CMF). With this regimen each patient was considered to be a reasonable “control” of herself. Blood cell count and natural killer cell activity (NKA) were tested on days 1, 8, 15, 22, and 23. Preliminary in vitro studies indicated that IL-2 or IFN antagonized the severe inhibition of NKA induced by hydroxy-peroxy-cyclophosphamide (in vitro active derivative of cyclophosphamide), alone or associated with methotrexate + 5-fluorouracil. Nine patients completed all six alternating cycles, whereas one patient proved to have metastatic lesions after four cycles. The protocol was well tolerated, although leukopenia (CMF alone) and leukopenia with fever and moderate or minimal flu-like symptoms (CMF + IL-2 + IFN) were generally observed. Treatment with IL-2 facilitated complete recovery of white cell counts and NKA after the nadir on day 15. In conclusion, the present protocol appears to be well tolerated and amenable to administration on an outpatient basis. Therefore, further investigations should be performed to verify whether CMF + IL-2 + IFN would be superior to CMF alone for adjuvant treatment after surgery in breast cancer. Received: 9 April 1998 / Accepted: 16 July 1998     

Molecular characterization,physicochemical properties,known and potential applications of phytases: An overview

Phytases (myo-inositol hexakisphosphate phosphohydrolases) hydrolyze the phosphate ester bonds of phytate-releasing phosphate and lower myo-inositol phosphates and/or myo-inositol. Phytases, in general, are known to enhance phosphate and mineral uptake in monogastric animals such as poultry, swine, and fish, which cannot metabolize phytate besides reducing environmental pollution significantly. In this study, the molecular, biophysical, and biochemical properties of phytases are reviewed in detail. Alterations in the molecular and catalytic properties of phytases, upon expression in heterologous hosts, are discussed. Diverse applications of phytases as feed additives, as soil amendment, in aquaculture, development of transgenic organisms, and as nutraceuticals in the human diet also are dealt with. Furthermore, phytases are envisaged to serve as potential enzymes that can produce versatile lower myo-inositol phosphates of pharmaceutical importance. Development of phytases with improved attributes is an important area being explored through genetic and protein engineering approaches, as no known phytase can fulfill all the properties of an ideal feed additive.     

A new salicylic acid-derivatized kojic acid vanadyl complex: synthesis, characterization and anti-diabetic therapeutic potential

The molecular mechanisms of vanadium toxicity suggest that incorporation of antioxidant groups in the structure of vanadium complexes could be a preferable strategy in designing novel hypoglycemic vanadium complexes with proper efficacy and safety. By conjugating a pyrone skeleton to provide a coordination group and antioxidative motifs, we synthesized a novel complex of bis ((5-hydroxy-4-oxo-4 H-pyran-2-yl) methyl 2-hydroxy- benzoatato) oxovanadium (IV) (BSOV). Evaluation of the anti-diabetic effects of BSOV using streptozotocin (STZ)-induced diabetic rats with bis (maltolato) oxovanadium (BMOV) as a positive control showed that BSOV effectively lowered blood glucose level, ameliorated damages of hepatic and renal function in diabetic rats and improved lipid metabolism. The signs of potential alteration of renal function caused by BSOV and BMOV were observed and are discussed. Overall, the experimental results suggest BSOV as a potent hypoglycemic agent and further studies using this strategy for anti-diabetic agents.     

Studies on the cytotoxic,apoptotic and antitumoral effects of Au(III) and Pt(II) complexes of 1, 10-phenanthroline on V79 379A and A549 cell lines

In the present study, Au(III) and Pt(II) complexes of 1, 10-phenanthroline (phen) were synthesized and used as the test compounds. The structure elucidation of the synthesized compounds was performed by IR, ¹H-NMR and MASS spectroscopic data and the results of elemental analyses. The cytotoxic and apoptotic effects of test compounds were elucidated on V79 379A (Chinese hamster lung fibroblast like) and A549 (human lung carcinoma epithelial like) cell lines. Cytotoxicity was measured with MTT assay and antitumoral effect was determined by colony forming ability methods. In addition, nuclear fragmentation and activation of apoptotic enzyme (caspase-3) and DAPI staining were used to detect the apoptotic effect of the compounds. All the test compounds induced time and concentration-dependent cytotoxic and antitumoral effects. Significant increases in the levels of apoptosis were observed with increasing exposure concentration.     

Anticancer phytochemical analogs 37: Synthesis,characterization, molecular docking and cytotoxicity of novel plumbagin hydrazones against breast cancer cells

We have synthesized, structurally characterized and examined cytotoxicity of novel plumbagin hydrazones against estrogen and progesterone receptor positive (ER+/PR+) MCF-7 and triple negative MDA-MB-231 breast cancer cell lines in order to evaluate the potential of these novel phytochemical analogs. Compounds were docked into the protein cavity of p50-subunit of NF-κB protein revealing better fit and better binding energies than the parent plumbagin compound. This was also reflected in their superior cytotoxicities which were found to be mediated by inhibition of NF-κB expression. These compounds can provide a starting point for the development of novel drug molecules against triple negative breast cancers.     

Optimization, purification and characterization of novel thermostable, haloalkaline, solvent stable protease from Bacillus halodurans CAS6 using marine shellfish wastes: a potential additive for detergent and antioxidant synthesis

A protease producing marine bacterium, Bacillus halodurans CAS6 isolated from marine sediments, was found to produce higher enzyme by utilizing shrimp shell powder. Optimum culture conditions for protease production were 50 °C, pH 9.0, 30 % NaCl and 1 % shrimp shell powder (SSP) and the protease purified with a specific activity of 509.84 U/mg. The enzyme retained 100 % of its original activity even at 70 °C, pH 10.0 and 30 % NaCl for 1 h. The purified protease exhibited higher stability when treated with ionic, non-ionic (72–94 %) and commercial detergents (76–88 %), and organic solvents (88–126 %). Significant blood stain removal activity was found with the enzyme in washing experiments. The culture supernatant supplemented with 1 % SSP showed 93.67 ± 2.52 % scavenging activity and FT-IR analysis of the reaction mixture confirmed the presence of antioxidants such as cyclohexane and cyclic depsipeptide with aliphatic amino groups. These remarkable qualities found with this enzyme produced by Bacillus halodurans CAS6 could make this as an ideal candidate to develop the industrial process for bioconversion of marine wastes and antioxidant synthesis.     

Cancer stem cell, niche and EGFR decide tumor development and treatment response: A bio-computational simulation study

Recent research in cancer biology has suggested the hypothesis that tumors are initiated and driven by a small group of cancer stem cells (CSCs). Furthermore, cancer stem cell niches have been found to be essential in determining fates of CSCs, and several signaling pathways have been proven to play a crucial role in cellular behavior, which could be two important factors in cancer development. To better understand the progression, heterogeneity and treatment response of breast cancer, especially in the context of CSCs, we propose a mathematical model based on the cell compartment method. In this model, three compartments of cellular subpopulations are constructed: CSCs, progenitor cells (PCs), and terminal differentiated cells (TCs). Moreover, (1) the cancer stem cell niche is, considered by modeling its effect on division patterns (symmetric or asymmetric) of CSCs, and (2) the EGFR signaling pathway is integrated by modeling its role in cell proliferation, apoptosis. Our simulation results indicate that (1) a higher probability for symmetric division of CSC may result in a faster expansion of tumor population, and for a larger number of niches, the tumor grows at a slower rate, but the final tumor volume is larger; (2) higher EGFR expression correlates to tumors with larger volumes while a saturation function is observed, and (3) treatments that inhibit tyrosine kinase activity of EGFR may not only repress the tumor volume, but also decrease the CSCs percentages by shifting CSCs from symmetric divisions to asymmetric divisions. These findings suggest that therapies should be designed to effectively control or eliminate the symmetric division of CSCs and to reduce or destroy the CSC niches.     

Production, characterization and evaluation of methylcellulose from sugarcane bagasse for applications as viscosity enhancing admixture for cement based material

In previous works, methylcellulose (MC) was prepared from sugarcane bagasse cellulose in heterogeneous medium using dimethyl sulfate (DMS) as etherification agent. MC was produced in a range of degrees of substitution (DS) from 0.70 to 1.40 and the materials showed low water solubility. In this work methylcellulose was prepared with 5 h (MC5h) of reaction with reagent substitution at each hour. MC5h showed a DS of 1.89 ± 0.04. An aqueous viscous suspension was produced with MC5h for application as viscosity enhancing admixture of cimentitious adhesive mortars. It was observed a 40.37% increase on the consistency index (CI) and a 27.70% increase on the Potential Tensile Adhesion Strength. Such characteristics show the potential of this material for the utilization in situations that require good workability, improve viscosity and adhesive properties such as for tile setting in civil engineering.     

Preparation and characterization of amino and carboxyl functionalized core-shell Fe3O4/SiO2 for L-asparaginase immobilization: A comparison study

Abstract

Magnetic nanoparticles are well known as facile and effective support for enzyme immobilization since they have a high surface area, large surface-to-volume ratio, easy separation, a fast and high enzyme loading. This study aims to provide insights on whether acidic or basic modified particles are more effective for L-asparaginase (ASNase) immobilization. Therefore, amino (Fe₃O₄/SiO₂/NH₂) and carboxyl-functionalized (Fe₃O₄/SiO₂/COOH) particles were prepared. The functional groups, crystalline structure, magnetic properties, morphology, chemical composition and thermal behaviour of the prepared modified nanoparticles were examined via Fourier-transform infra-red spectroscopy (FTIR), X-ray diffraction (XRD), vibrating-sample magnetometer (VSM), scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDAX). Under the optimum conditions, the immobilized enzymes were more stable within a certain range of temperatures and pH values in comparison to free enzyme. On the other hand, the immobilized enzymes showed greater stability after incubation for 3?h at 50?°C. The free enzyme maintained only 30% of its initial activity for 4?weeks at 4?°C, while Fe₃O₄/SiO₂/NH₂/ASNase and Fe₃O₄/SiO₂/COOH/ASNase retained more than 78.9% and 56.5% of initial activities under the same conditions, respectively. Moreover, Fe₃O₄/SiO₂/NH₂/ASNase (77.2%) and Fe₃O₄/SiO₂/COOH/ASNase (57.4%) displayed excellent operational stability after 17 repeated cycles. These findings suggested that the Fe₃O₄/SiO₂/NH₂ and Fe₃O₄/SiO₂/COOH may be utilized as efficient and sustainable supports to developed immobilized ASNase in several biotechnological applications.     

A potential new prodrug for the treatment of cystinosis: design, synthesis and in-vitro evaluation

Nephropathic cystinosis is a rare autosomal recessive disease characterised by raised lysosomal levels of cystine in the cells of most organs. The disorder is treated by regular administration of the aminothiol, cysteamine, an odiferous and unpleasant tasting compound that along with its metabolites is excreted in breath and sweat, leading to poor patient compliance. In an attempt to improve patient compliance a series of novel prodrugs has been designed and evaluated as a potential new treatment for nephropathic cystinosis. The first of the prodrugs tested, 3a, was found to decrease the levels of intracellular cystine in cystinotic fibroblasts. This is the first report of a potential new therapeutic treatment for nephropathic cystinosis since the advent of cysteamine bitartrate.     

A pilot replication study of two PER3 single nucleotide polymorphisms as potential genetic markers for morning and evening earliness-lateness

Polymorphisms in genes of circadian system family seem to be of most importance for understanding of mechanisms underlying self-assessed individual variation in morning–evening preference. A review of earlier reported positive findings indicated that, at least, four polymorphisms in period circadian clock 3 (PER3) showed significant association with, at least, one of sub-constructs of a morningness–eveningness scale. However, similar to other candidate gene studies, these studies suffer from increased likelihood of false positive findings. We tried to replicate some of the most recently published positive results on associations of sub-traits of morningness–eveningness with two PER3 non-synonymous single nucleotide polymorphisms. DNA from buccal swabs was collected from healthy residents of three Russian cities, Moscow (N = 149) and Novosibirsk and Stavropol (N = 248). The tested hypotheses were formulated in accord with the earlier reported positive findings: the rare alleles might be linked to a higher score on (i) morning earliness–lateness scale (rs2640909, Moscow data-set) and (ii) both morning and evening earliness–lateness scales (rs228729, Novosibirsk and Stavropol datasets). The results provided support for the former hypothesis. These and earlier reported results highlighted several critical issues that remained to be addressed in future independent replications of positive findings on potential genetic markers for morning and evening earliness–lateness.     

Circulating tumour cells and cancer stem cells: A role for proteomics in defining the interrelationships between function,phenotype and differentiation with potential clinical applications

Research on the discovery and implementation of valid cancer biomarkers is one of the most challenging fields in oncology and oncoproteomics in particular. Moreover, it is generally accepted that an evaluation of cancer biomarkers from the blood could significantly enable biomarker assessments by providing a relatively non-invasive source of representative tumour material. In this regard, circulating tumour cells (CTCs) isolated from the blood of metastatic cancer patients have significant promise. It has been demonstrated that localised and metastatic cancers may give rise to CTCs, which are detectable in the bloodstream. Despite technical difficulties, recent studies have highlighted the prognostic significance of the presence and number of CTCs in the blood. Future studies are necessary not only to detect CTCs but also to characterise them. Furthermore, another pathogenically significant type of cancer cells, known as cancer stem cells (CSCs) or more recently termed circulating tumour stem cells (CTSCs), appears to have a significant role as a subpopulation of CTCs.