Thiol-Disulfide Exchange Reaction Promoted Highly Efficient Cellular Uptake of Pyridyl Disulfide Appended Nonionic Polymers.

The intracellular transport of molecules, macromolecules or materials is a key step in probing cellular structure and function, as well as regulating a plethora of physical and chemical events for treating disease. This communication reveals direct cellular uptake of pyridyl-disulfide (Py-Ds)-conjugated nonionic and biocompatible macromolecules with the aid of rapid exchange of the highly reactive Py-Ds groups with exofacial cell-surface thiols. Confocal microscopy and flow cytometry analysis confirmed highly efficient cellular uptake of Py-Ds-appended polymers (>50 % in 15 min) by avoiding lysosome as a consequence of thiol-disulfide exchange in the cell surface. In contrast, a control polymer lacking the Py-Ds group followed caveolae-mediated endocytosis. Other control polymers containing either the pyridine group (but not disulfide) or the disulfide group (but not pyridine) revealed significantly low cellular uptake, and thus essential role of the highly reactive Py-Ds group was established beyond doubt.

Characterization of a novel family VIII esterase EstM2 from soil metagenome capable of hydrolyzing estrogenic phthalates.

BACKGROUND: Microbes are rich sources of enzymes and esterases are one of the most important classes of enzymes because of their potential for application in the field of food, agriculture, pharmaceuticals and bioremediation. Due to limitations in their cultivation, only a small fraction of the complex microbial communities can be cultured from natural habitats. Thus to explore the catalytic potential of uncultured organisms, the metagenomic approach has turned out to be an effective alternative method for direct mining of enzymes of interest. Based on activity-based screening method, an esterase-positive clone was obtained from metagenomic libraries. RESULTS: Functional screening of a soil metagenomic fosmid library, followed by transposon mutagenesis led to the identification of a 1179 bp esterase gene, estM2, that encodes a 392 amino acids long protein (EstM2) with a translated molecular weight of 43.12 kDa. Overproduction, purification and biochemical characterization of the recombinant protein demonstrated carboxylesterase activity towards short-chain fatty acyl esters with optimal activity for p-nitrophenyl butyrate at pH 8.0 and 37 °C. Amino acid sequence analysis and subsequent phylogenetic analysis suggested that EstM2 belongs to the family VIII esterases that bear modest similarities to class C ß-lactamases. EstM2 possessed the conserved S-x-x-K motif of class C ß-lactamases but did not exhibit ß-lactamase activity. Guided by molecular docking analysis, EstM2 was shown to hydrolyze a wide range of di- and monoesters of alkyl-, aryl- and benzyl-substituted phthalates. Thus, EstM2 displays an atypical hydrolytic potential of biotechnological significance within family VIII esterases. CONCLUSIONS: This study has led to the discovery of a new member of family VIII esterases. To the best of our knowledge, this is the first phthalate hydrolase (EstM2), isolated from a soil metagenomic library that belongs to a family possessing ß-lactamase like catalytic triad. Based on its catalytic potential towards hydrolysis of both phthalate diesters and phthalate monoesters, this enzyme may find use to counter the growing pollution caused by phthalate-based plasticizers in diverse geological environment and in other aspects of biotechnological applications.

Fluorescent PEGulated Oligourethane Nanoparticles for Long-Term Cellular Tracing.

We have introduced a new ABA-type amphiphilic block copolymer consisting of functional oligourethane hydrophobic blocks and two polyethylene glycol (PEG) hydrophilic blocks. The polymer was synthesized in a single step by step-growth polymerization between two monomers, namely tetraphenylethylene (TPE)-diol and hexamehylene di-isocyanate in the presence of a monofunctional impurity PEG-2000. The polymer exhibits facile self-assembly in water by synergistic effects of H-bonding and π-π interaction among the oligourethane core, leading to the formation of robust nanoparticles with remarkable aggregation-induced emission (AIE). These nanoparticles show very low critical aggregation concentration, stability over a large pH window, and excellent biocompatibility as revealed by an MTT assay. Cellular imaging with cancer cells showed facile cellular uptake and, more importantly, retention of AIE in cellular milieu for long times, which was successfully utilized for long-term cancer cell tracking.

Metabolism of 2-hydroxy-1-naphthoic acid and naphthalene via gentisic acid by distinctly different sets of enzymes in Burkholderia sp. strain BC1.

Burkholderia sp. strain BC1, a soil bacterium, isolated from a naphthalene balls manufacturing waste disposal site, is capable of utilizing 2-hydroxy-1-naphthoic acid (2H1NA) and naphthalene individually as the sole source of carbon and energy. To deduce the pathway for degradation of 2H1NA, metabolites isolated from resting cell culture were identified by a combination of chromatographic and spectrometric analyses. Characterization of metabolic intermediates, oxygen uptake studies and enzyme activities revealed that strain BC1 degrades 2H1NA via 2-naphthol, 1,2,6-trihydroxy-1,2-dihydronaphthalene and gentisic acid. In addition, naphthalene was found to be degraded via 1,2-dihydroxy-1,2-dihydronaphthalene, salicylic acid and gentisic acid, with the putative involvement of the classical nag pathway. Unlike most other Gram-negative bacteria, metabolism of salicylic acid in strain BC1 involves a dual pathway, via gentisic acid and catechol, with the latter being metabolized by catechol 1,2-dioxygenase. Involvement of a non-oxidative decarboxylase in the enzymic transformation of 2H1NA to 2-naphthol indicates an alternative catabolic pathway for the bacterial degradation of hydroxynaphthoic acid. Furthermore, the biochemical observations on the metabolism of structurally similar compounds, naphthalene and 2-naphthol, by similar but different sets of enzymes in strain BC1 were validated by real-time PCR analyses.

Extracellular Matrix Mimicking Wound Microenvironment Responsive Amyloid-Heparin@TAAgNP Co-Assembled Hydrogel: An Effective Conductive Antibacterial Wound Healing Material.

Bioengineered composite hydrogel platforms made of a supramolecular coassembly have recently garnered significant attention as promising biomaterial-based healthcare therapeutics. The mechanical durability of amyloids, in conjunction with the structured charged framework rendered by biologically abundant key ECM component glycosaminoglycan, enables us to design minimalistic customized biomaterial suited for stimuli responsive therapy. In this study, by harnessing the heparin sulfate-binding aptitude of amyloid fibrils, we have constructed a pH-responsive extracellular matrix (ECM) mimicking hydrogel matrix. This effective biocompatible platform comprising heparin sulfate-amyloid coassembled hydrogel embedded with polyphenol functionalized silver nanoparticles not only provide a native skin ECM-like conductive environment but also provide wound-microenvironment responsive on-demand superior antibacterial efficacy for effective diabetic wound healing. Interestingly, both the cytocompatibility and antibacterial properties of this bioinspired matrix can be fine-tuned by controlling the mutual ratio of heparin sulfate-amyloid and incubated silver nanoparticle components, respectively. The designed biomaterial platform exhibits notable effectiveness in the treatment of chronic hyperglycemic wounds infected with multidrug-resistant bacteria, because of the integration of pH-responsive release characteristics of the incubated functionalized AgNP and the antibacterial amyloid fibrils. In addition to this, the aforementioned assemblage shows exceptional hemocompatibility with significant antibiofilm and antioxidant characteristics. Histological evidence of the incised skin tissue sections indicates that the fabricated composite hydrogel is also effective in controlling pro-inflammatory cytokines such as IL6 and TNFα expressions at the wound vicinity with significant upregulation of angiogenesis markers like CD31 and α-SMA.

Multi-Faceted Antimicrobial Efficacy of a Quinoline-Derived Bidentate Copper(II) Ligand Complex and Its Hydrogel Encapsulated Formulation in Methicillin-Resistant Staphylococcus aureus Inhibition and Wound Management.

The emergence of antimicrobial resistance, exemplified by methicillin-resistant Staphylococcus aureus (MRSA), poses a grave threat to public health globally. Over time, MRSA has evolved resistance to multiple antibiotics, challenging conventional treatment strategies. The relentless adaptability of MRSA underscores the urgent need for innovative and targeted antimicrobial approaches to combat this resilient pathogen. Ancient knowledge and practices, along with scientific evidence, have established that metallic copper, and its organic coordination complexes can act as potential antibacterial substances. In search of a smart and effective antimicrobial against MRSA, we designed, synthesized, and characterized a bidentate copper(II) ligand complex (SG-Cu) utilizing a comprehensive array of analytical techniques, including ESI-MS, elemental analysis, X-ray photoelectron spectroscopy, electron paramagnetic resonance spectroscopy, and others. Antibacterial efficacy and mechanism of action of the complex were assessed through bacterial growth analyses, bacterial membrane perturbation assays, ROS elicitation assays, and field emission scanning electron microscopy. SG-Cu was found to maintain robust biocompatibility against the mammalian cell lines HEK-293, WI-38, and NIH/3T3. Remarkably, SG-Cu demonstrated significant biofilm disruptive tendency evidenced by the retardation of sliding motility, reduction in slime production, reduction in biofilm viability, and enhanced biofilm eradication, both in vitro and in urinary catheters. In vivo studies on murine excisional wounds, with SG-Cu impregnated in a palmitic acid conjugated NAVSIQ hexapeptide (PA-NV) hydrogel, revealed the sustained release of SG-Cu from the gel matrix, facilitating accelerated wound healing and effective wound disinfection. This multifaceted investigation highlights the potential of SG-Cu as a versatile option for combating MRSA infections and promoting wound healing, solidifying its claim to be developed into a viable therapeutic.

Synergistic Augmentation of Beta-Lactams: Exploring Quinoline-Derived Amphipathic Small Molecules as Antimicrobial Potentiators against Methicillin-Resistant Staphylococcus aureus.

The escalation of bacterial resistance against existing therapeutic antimicrobials has reached a critical peak, leading to the rapid emergence of multidrug-resistant strains. Stringent pathways in novel drug discovery hinder our progress in this survival race. A promising approach to combat emerging antibiotic resistance involves enhancing conventional ineffective antimicrobials using low-toxicity small molecule adjuvants. Recent research interest lies in weak membrane-perturbing agents with unique cyclic hydrophobic components, addressing a significant gap in antimicrobial drug exploration. Our study demonstrates that quinoline-based amphipathic small molecules, SG-B-52 and SG-B-22, significantly reduce MICs of selected beta-lactam antibiotics (ampicillin and amoxicillin) against lethal methicillin-resistant Staphylococcus aureus (MRSA). Mechanistically, membrane perturbation, depolarization, and ROS generation drive cellular lysis and death. These molecules display minimal in vitro and in vivo toxicity, showcased through hemolysis assays, cell cytotoxicity analysis, and studies on albino Wistar rats. SG-B-52 exhibits impressive biofilm-clearing abilities against MRSA biofilms, proposing a strategy to enhance beta-lactam antibiosis and encouraging the development of potent antimicrobial potentiators.

Amyloid-Inspired Engineered Multidomain Amphiphilic Injectable Peptide Hydrogel─An Excellent Antibacterial, Angiogenic, and Biocompatible Wound Healing Material.

The ingrained mechanical robustness of amyloids in association with their fine-tunable physicochemical properties results in the rational design and synthesis of tailor-made biomaterials for specific applications. However, the incredible antimicrobial efficacy of these ensembles has largely been overlooked. This research work provides an insight into the interplay between self-assembly and antimicrobial activity of amyloid-derived peptide amphiphiles and thereby establishes a newfangled design principle toward the development of potent antimicrobial materials with superior wound healing efficacy. Apart from the relationship with many neurodegenerative diseases, amyloids are now considered as an important cornerstone of our innate immune response against pathogenic microbes. Impelled by this observation, a class of amphiphilic antimicrobial peptide-based biomaterial has been designed by taking Aß42 as a template. The designed AMP due to its amphipathic nature undergoes rapid self-assembly to form a biocompatible supramolecular hydrogel network having significant antibacterial as well as wound healing effectivity on both Gram-negative P. aeruginosa and MRSA-infected diabetic wounds via reduced inflammatory response and enhanced angiogenesis. Results suggest that disease-forming amyloids can be used as a blueprint for the fabrication of biomaterial-based antimicrobial therapeutics by fine-tuning both the hydrophobicity of the ß-aggregation prone zone as well as membrane interacting cationic residues.

Potential Broad-Spectrum Antimicrobial, Wound Healing, and Disinfectant Cationic Peptide Crafted from Snake Venom.

Antimicrobial cationic peptides are intriguing and propitious antibiotics for the future, even against multidrug-resistant superbugs. Venoms serve as a source of cutting-edge therapeutics and innovative, unexplored medicines. In this study, a novel cationic peptide library consisting of seven sequences was designed and synthesized from the snake venom cathelicidin, batroxicidin (BatxC), with the inclusion of the FLPII motif at the N-terminus. SP1V3_1 demonstrated exceptional antibacterial effectiveness against Escherichia coli, methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, and Klebsiella pneumoniae and destroyed the bacteria by depolarizing, rupturing, and permeabilizing their membranes, as evident from fluorescence assays, atomic force microscopy, and scanning electron microscopy. SP1V3_1 was observed to modulate the immune response in LPS-elicited U937 cells and exhibited good antibiofilm activity against MRSA and K. pneumoniae. The peptide promoted wound healing and disinfection in the murine model. The study demonstrated that SP1V3_1 is an exciting peptide lead and may be explored further for the development of better therapeutic peptides.

Self-Assembled Polyurethane Capsules with Selective Antimicrobial Activity against Gram-Negative E. coli.

This article reports the antimicrobial activity of two segmented amphiphilic polyurethanes, PU-1 and PU-2, containing a primary or secondary amine group, respectively. In acidic water, intrachain H-bonding among the urethanes followed by hierarchical assembly resulted in the formation of capsules (Dh = 120 ± 20 and 100 ± 17 nm for PU-1 and PU-2, respectively) with a highly positive surface charge. They showed selective interactions with bacterial cell mimicking liposomes over mammalian cell mimicking liposomes with favorable enthalpy and entropy contributions, which was attributed to the electrostatic interaction and hydrophobic effect. Antimicrobial studies with Escherichia coli revealed very low minimum inhibitory concentration (MIC) values of 7.8 and 15.6 µg/mL for PU-1 and PU-2, respectively, indicating their ability to efficiently kill Gram-negative bacteria. Killing of Gram-positive Staphylococcus aureus was noticed only at C = 500 µg/mL, indicating unprecedented selectivity for E. coli, which was further confirmed by scanning electron microscopy (SEM) studies. Hemolysis assay revealed HC50 values of 453 and 847 µg/mL for PU-1 and PU-2, respectively, which were >50 times higher than their respective MIC values, thus making them attractive antimicrobial materials. Ortho-nitrophenyl-ß-galactoside (ONPG) assay and live-dead fluorescence assay confirmed that for both the polymers, a membrane disruption pathway was operative for wrapping of the bacterial membrane, similar to what was proposed for antimicrobial peptides. SEM images of polymer-treated E. coli bacteria helped in visualization of the pore formation and the disrupted membrane structure.

Directional Supramolecular Assembly of π-Amphiphiles with Tunable Surface Functionality and Impact on the Antimicrobial Activity.

This article elucidates H-bonding-regulated directional supramolecular assembly of naphthalene diimide (NDI)-derived unsymmetric cationic bola-shaped π-amphiphiles and systematic investigations on the thermodynamics of their interaction with bacteria mimic lipid vesicles and antimicrobial activity with mechanistic insights. Four NDI-amphiphiles (NDI-1, NDI-2, NDI-3, and NDI-2a) have been studied, all of which contain a central NDI chromophore, a nonionic wedge, an amine containing a head group, and a hydrazide group. In NDI-2 and NDI-2a, the hydrophilic wedge and the head group (pyridine) are the same but the location of the hydrazide group is different. On the basis of this difference, the pyridyl groups are displayed at the outer and inner walls of the vesicle, respectively. Isothermal titration calorimetry (ITC) studies revealed the spontaneous interaction of NDI-2 assembly with bacteria membrane mimic DPPE liposome (ΔG = -6.35 kcal/mol), whereas the NDI-2a assembly did not interact at all, confirming a strong influence of the H-bonding-regulated functional group display. On the other hand, the location of the hydrazide group remains the same in NDI-1, NDI-2, and NDI-3, but they differ in the head group structure. ITC binding studies confirmed spontaneous interaction of all three assemblies with DPPE liposome with negative ΔG values following the order NDI-1 > NDI-2 > NDI-3, indicating significant influence of the structure of the head group on the interaction with the model membrane. In fact, in all cases, the interaction was favorable both by enthalpy and entropy contribution, indicating dual involvement of the electrostatic interaction and hydrophobic effect. Notably, ΔS value for NDI-1 containing a tertiary amine head group was found to be significantly higher than that for NDI-3 containing a primary amine, which is attributed to the enhanced hydrophobic effect in the former case. Furthermore, ITC experiments revealed no interaction by any of these assemblies with the mammalian cell membrane mimic liposome, indicating their high selectivity toward bacterial membranes. Antimicrobial activity studies showed NDI-2 to be lethal selectively against Gram-positive bacteria, whereas NDI-2a did not show any activity. NDI-3 with a primary amine showed moderate activity but no selectivity over the erythrocytes. NDI-1 with the tertiary amine group was found to be the most outstanding candidate, exhibiting broad-spectrum antimicrobial activity with very low minimum inhibitory concentration values of 15.8 and 62 µg/mL for Staphylococcus aureus and Escherichia coli, respectively, and high selectivity over erythrocytes. These results fully corroborate with the physical insights obtained from the ITC studies on their interaction with the model liposome. Control molecules, lacking either the NDI chromophore or the hydrazide nonionic containing wedge, did not exhibit any notable antibacterial activity. Live-dead assay with fluorescence microscopy studies indicated that the antimicrobial activity of NDI-1 operates through the membrane disruption pathway similar to that of the host defense peptides.

pH-Responsive Biocompatible Supramolecular Peptide Hydrogel.

Peptide-based hydrogels are highly promising for various biomedical applications owing to their precise self-assembly, biocompatibility, and sensitivity toward biologically relevant external stimuli. Herein, we report pH-responsive self-assembly and gelation of a highly biocompatible amphiphilic peptide PEP-1. This is an octa-peptide and double mutant of a naturally occurring ß-strand peptide fragment of the protein Galectin-1, available in bovine spleen. PEP-1 was synthesized by using the Rink amide resin as the solid support in a homemade apparatus. At pH 7.4, it exhibits spontaneous gelation with very high yield stress of 88.0 Pa and gel-to-sol temperature of 84 °C at C = 2.0 wt %. Microscopy studies revealed entangled fibrillar morphology whereas circular dichroism, Fourier tranform IR, and Thioflavin T assay indicated formation of ß-sheet rich secondary structure. The assembled state was found to be stable in neutral pH whereas either decrease or increase in the pH resulted in disassembly owing to the presence of the pH responsive Asp and Lys residues. The gel network showed ability to entrap water-soluble guest molecules such as Calcein which could be selectively released at acidic pH whereas under neutral condition the release was negligible. MTT assay revealed remarkable biocompatibility of the PEP-1 gel as almost 100% cells were alive after 48 h incubation in the presence of PEP-1 (2.0 mg/mL).

Solvent switchable nanostructures and the function of a π-amphiphile.

This manuscript reports solvent tunable functional nano-assemblies of an unsymmetrical bola-shaped π-amphiphile (NDI-PY) which consists of a hydrophobic naphthalene-diimide (NDI) chromophore connected to a non-ionic hydrophilic wedge and a pyridine group at its two opposite arms. Importantly, it contains a hydrazide group located at the hydrophobic domain between the NDI-chromophore and the hydrophilic-wedge to drive the supramolecular assembly by directional H-bonding. NDI-PY exhibits spontaneous assembly in water as well as in a highly non-polar solvent like tetra-chloroethylene (TCE) by the synergistic effect of H-bonding and π-stacking interaction. Spectroscopy studies reveal almost identical self-assembly features in water and TCE with critical aggregation concentrations in the range of 0.3 mM, which matches the values obtained from the isothermal calorimetry (ITC) dilution experiment. Differential scanning calorimetry (DSC) experiments reveal a single endothermic peak at 31 °C (ΔH = -12.3 kJ mol-1) and 40 °C (ΔH = -5.35 kJ mol-1) for water and TCE, respectively, indicating marginally higher thermal stability in TCE, which is consistent with the FT-IR data, suggesting stronger H-bonding in TCE. Although the molecular assembly features appear to be similar, NDI-PY produces distinctly different mesoscopic structures in water and TCE. In water, it forms vesicles (Dh = 150-180 nm) with the pyridine groups displayed at the outer surface, while in TCE it generates a transparent gel (CGC = 8.0 mM) with a nanotubular (width ∼50 nm, wall thickness ∼10 nm) morphology. Powder X-ray diffraction studies show clearly different packing structures; in water a single sharp peak at the low angle (d = 19.3 Å, a little shorter than the extended length of the molecule) suggests the formation of a monolayer membrane, while in TCE several sharp peaks appear with the d values maintaining a ratio of 1 : 1/√3 : 1/2 : 1/√7 : 1/3 : 1/√12, indicating the formation of a 2D hexagonal lattice. Photoconductivity measurements reveal moderate electronic conduction in both cases. However, it shows a remarkable enhancement of the life time of the charge-carriers for the nanotubular structure compared to the vesicular morphology. On the other hand, the vesicles in water display antimicrobial activity against Gram-positive S. aureus with a highly promising MICLB value of 29.4 µg mL-1. In contrast, it does not lyse human red blood cells even at as high a concentration as 2.5 mg mL-1 (HC50 > 2.5 mg mL-1), implying high selectivity of the NDI-PY vesicles towards bacterial cells over mammalian cells. Display of the pyridine groups at the outer surface of the membrane enables molecular recognition by complementary H-bonding with a carboxylic acid group and thereby facilitates uptake of the attached pyrene chromophores in the NDI-membrane by charge-transfer interaction between the NDI acceptor and the pyrene donor. In fact a Job's plot experiment reveals maximum uptake at a 1 : 1 ratio of the NDI-PY and the pyrene guest, indicating all the pyridine groups are accessible at the vesicular surface.

Morphology Regulation in Redox Destructible Amphiphilic Block Copolymers and Impact on Intracellular Drug Delivery.

In two ABA type amphiphilic block copolymers (P1, P2), the hydrophobic B block consists of a bioreducible segmented poly(disulfide) (PDS), while poly-N-isopropylacrylamide (PNIPAM) or poly(triethyleneglycol)methylether-methacrylate (PTEGMA) serve as the hydrophilic A blocks in P1 and P2, respectively, leading to the formation of polymersome and micelle, owing to the difference in the packing parameters. Both exhibit comparable doxorubicin (Dox) encapsulation efficiency, but glutathione (GSH) triggered release appears much faster from the polymersome than micelle owing to the complete degradation of the PDS segment in polymersome morphology unlike in micelle. Dox-loaded polymers (P1-Dox and P2-Dox) exhibit minimum toxicity to normal cells like C2C12. By contrast, P1-Dox shows excellent killing efficiency to the HeLa cells (cancer cell) (in which the GSH concentration is significantly higher). However, P2-Dox reveals a rather poor activity even to HeLa cells. Fluorescence microscopy studies show comparable cellular uptake of P1-Dox and P2-Dox. But the polymersome entrapped dye escapes fast from the cargo and reach the nucleus, while the drug-loaded micelle remains trapped in the perinuclear zone explaining the significant difference in the drug delivery performance of polymersome and micelle.

Hemodynamic response to endotracheal intubation using C-Trach assembly and direct laryngoscopy.

PURPOSE: Our objective was to study the pressor response to endotracheal intubation through laryngeal mask airway C-Trach and compare it to the hemodynamic response to intubation with direct laryngoscopy (DL). MATERIALS AND METHODS: After obtained approval from institutional ethical committee, 100 patients of American Society of Anesthesiologists physical Status I, aged 14-65 years, posted for elective surgery were enrolled in the trial. They were randomly divided into two groups of each 50 patients. Anesthesia technique was standardized and patients of Group I were intubated using DL, while patients of Group II were intubated with the help of C-Trach assembly. Hemodynamic parameters, systemic blood pressure (systolic and diastolic) and heart rate were recorded before and after induction of anesthesia and every minute up to 5 min after intubation. RESULTS: Patients of Group II recorded a minimal rise in peak systolic blood pressure (SBP) (1.8%) and diastolic blood pressure (10.6%). In comparison patients of Group I recorded a significant sustained rise in peak SBP (20.3%) and diastolic blood pressure (21.4%). However heart rate changes recorded in the two groups were of equal measure (peak rise of 22.9% in Group I vs. 22.4% in Group II). CONCLUSION: We conclude that intubation through C-Trach generates a lower pressor response to intubation in comparison to intubation using DL.

A short GC rich DNA derived from microbial origin targets tubulin/microtubules and induces apoptotic death of cancer cells.

A short GC rich DNA derived from microbial origin interacts with tubulin/microtubules activates p53 over expression and induces apoptotic death of human breast cancer (MCF-7) cells.

Complete degradation of di-n-octyl phthalate by Gordonia sp. strain Dop5.

The present study describes the assimilation of di-n-octyl phthalate by an aerobic bacterium, isolated from municipal waste-contaminated soil sample utilizing di-n-octyl phthalate as the sole source of carbon and energy. The isolate was identified as Gordonia sp. based on the morphological, nutritional and biochemical characteristics as well as 16S rRNA gene sequence analysis. A combination of chromatographic and spectrometric analyses revealed a complete di-n-octyl assimilation pathway. In the degradation process, mono-n-octyl phthalate, phthalic acid, protocatechuic acid and 1-octanol were identified as the degradation products of di-n-octyl phthalate. Furthermore, phthalic acid was metabolized via protocatechuic acid involving protocatechuate 3,4-dioxygenase while 1-octanol was metabolized by NAD(+)-dependent dehydrogenases to 1-octanoic acid, which was subsequently degraded via ß-oxidation, ultimately, leading to tricarboxylic acid cycle intermediates. Apart from phthalic acid and 1-octanol metabolizing pathway enzymes, two esterases, di-n-octyl phthalate hydrolase and mono-n-octyl phthalate hydrolase involved in di-n-octyl phthalate degradation were found to be inducible in nature. This is the first report on the metabolic pathway involved in the complete degradation of di-n-octyl phthalate by a single bacterial isolate, which is also capable of efficiently degrading other phthalate esters of environmental concern having either shorter or longer alkyl chains.