In the cardiovascular diseased (CVD) conditions, it is essential to choose a suitable rheological model for capturing the correct physics behind the hemodynamic in the multiply afflicted diseased arterial network. This study investigates the effect of blood rheology on hemodynamics in a blood vessel with abdominal aortic aneurysm (AAA) and right internal iliac stenosis (RIIAS). A model with AAA and RIIAS is reconstructed from a human subject's computed tomography (CT) data. Localized mesh generation and pulsatile inflow condition are considered. Non-Newtonian models such as the Power-law, Carreau, Cross, and Herschel Berkley models are used in simulations. The outcome from a validated computational model is compared with the Newtonian model to identify the suitable model for dealing with pathological complications under consideration. The capabilities and significance of various rheological models are also examined via Wall Pressure (WP), Wall Shear Stress (WSS), velocity, Global non-Newtonian importance factor (IG), Vorticity Streamlines, and Swirling Strength. It is noted that during the entire cardiac cycle, the IG factor of the cross model is found to be relatively more significant. Power Law depicts larger IG factor during peak systole and early diastole. Also, the cross model depicts larger WSS, WPS, swirling strength distribution and vorticity during the peak systolic and diastolic phases It is noted that IG ∼0.02 is an appropriate non-Newtonian blood activity cut-off value in the descending abdominal artery having AAA and RIIAS. The critical important WSS values are in the range of 0-9 Pa which is stated in WSS contour plot.

New imaging methods have enabled the detection of unruptured abdominal aortic aneurysms (AAA). It is necessary to develop appropriate mathematical models for rupture prediction to allow a proper patient treatment plan. To provide valid hemodynamic parameters, high-fidelity numerical models with patient-specific boundary conditions are needed. Researchers have pointed out in recent research articles and reviews that those morphological parameters, such as shape, dilation ratio, neck angle, common iliac bifurcation angle, and AAA type, consistently correlate with the rupture mechanism. However, it is unclear how morphological indicators affect hemodynamics-based computational fluid dynamics predictions. The present work investigates the influence of AAA shape on local and global hemodynamics parameters and rupture predictions. Five cases of magnetic resonance imaging scan-based data for patient-specific aortofemoral artery modeling are explored. The inflow conditions are patient-specific, and an open loop system has been considered to model all five cases. Hemodynamics parameters in pulsating conditions, such as wall shear stress (WSS), velocity contour, time average WSS (TAWSS), oscillatory shear index (OSI), vorticity, and streamlines, are computed and investigated. Both maximum dilation diameter and aneurysm neck angle are found to have substantial effects on local hemodynamics parameters. The magnitude of WSS, TAWSS, and OSI increases and decreases non-linearly with a change in maximum diameter during the cardiac process. Also, aneurysms with doubly titled and completely saccular shape show complex streamlines, low WSS, and high residence time in the sac area of the wall.

The study of patient-specific human arterial flow dynamics is well known to face challenges like a) apt geometric modelling, b) bifurcation zone meshing, and c) capturing the hemodynamic prone to variations with multiple disease complications. Due to aneurysms and stenosis in the same arterial network, the blood flow dynamics get affected, which needs to be explored. This study develops a new protocol for accurate geometric modelling, bifurcation zone meshing and numerically investigates the arterial network with abdominal aortic aneurysms (AAA) and right internal iliac stenosis (RIIAS). A realistic arterial model is reconstructed from the computed tomography (CT) data of a human subject. To understand the combined effect of the aneurysm and aortoiliac occlusive diseases in a patient, an arterial network with AAA, RIIAS, multiple branches tapering, and curvature has been considered. Clinically significant pulsatile blood flow simulations have been carried out to trace the alteration in the flow dynamics with multiple pathological complications under consideration. The transient blood flow dynamics are investigated via wall shear stress, wall pressure, velocity contour, streamlines, vorticity, and swirling strength. During the systolic deceleration phase, the rhythmic nested rapid secondary oscillatory WSS, adverse pressure gradients, high WSS, and high WP bands are noticed. Also, the above studies will help researchers, clinicians, and doctors understand the influence of morphological changes on hemodynamics in cardiovascular studies.

Brown algae produce varieties of potent metabolites in order to adapt to extreme environment. Among these metabolites, polyphenols comprised of phlorotannins serve as powerful multifaceted bioactive with vast pharmacological potentials against non-communicable diseases like cancer and diabetes. In this study, a new phlorotannin was extracted from Padina tetrastromatica and characterized by Fourier Transform-Infrared, Nuclear Magnetic Resonance & Electronspray Ionization-Mass Spectroscopy. The phlorotannin exhibited potent DPPH and nitric oxide radical-scavenging activity in in-vitro, which were better than the standard antioxidants and other phlorotannins, previously reported. Further, the novel phlorotannin explicitly inhibited advanced glycation end-products formation in both in-vitro and in-vivo studies using hyperglycaemic C. elegans as an animal model and confirmed by live-cell fluorescence imaging. In addition, a significant modulation in expression of stress-responsive genes daf-2 and daf-16 were observed in phlorotannin treated hyperglycemic C. elegans. Moreover, the cytotoxic potential of phlorotannin (2,4,6-trioxa-1,3,5(1,3) tribenzenacyclohexaphane-15,35,55-triol) was explored for the first time in human cervical cancer cells (HeLa) and interesting observation was made that the cancer cell death was induced by activation of autophagy and pro-apoptotic protein markers i.e., LC3I/II, p21 and p53 that were confirmed by western-blot technique. Therefore, phlorotannin can be postulated as a potential bioactive for oxidative stress-mediated diseases, including diabetes and cancer.

Marine natural bioactive compounds have chemical diversities, which can be used to develop new potent drugs for various diseases. In this study, Lyngbya sp. (cyanobacterium), was used to explore for its biological potential against inflammation and cancer. (9S,E)-8-ethyl-9-methylnonadec-6-en-3-one (EME), was extracted from Lyngbya sp., purified, and characterized by different spectroscopic techniques. In addition, EME was assessed for the antiinflammatory potential by Fluorescence Activated Cell Sorting Analysis (FACS) in Lipopolysaccharide (LPS) induced RAW 264.7 macrophage cell lines, and a significant reduction in COX-2 expression was observed. Further, COX-2, TNF-alpha, iNOS, NF-kappa beta, and IL-1 beta gene expressions were also analysed in EME treated LPS induced RAW 264.7 cell line by semi-quantitative PCR. Subsequently, to enhance the availability of EME into the cells for the anti-inflammatory potential, it was blended with aminated mesoporous silica nanoparticles (MSNPs). The expressions of COX-2, TNF-alpha, iNOS, NF-kappa beta, and IL-1 beta were significantly downregulated in EME + MSNPs treated LPS induced RAW 264.7 cells. Conclusively, EME combined with MSNPs showed the therapeutic potential of an antiinflammatory agent. Furthermore, the cytotoxic activity of EME was also explored in cervical (HeLa) and liver cancer (HepG2) cell lines; the western blotting results witnessed that EME had induced the expressions of p53, caspase-3, and p21.

[This corrects the article DOI: 10.1021/acsomega.8b02085.].

Marine brown macroalgae are known for producing potent bioactive secondary metabolites such as phlorotannins. Phlorotannins are the phenolic compounds which can inhibit the oxidative stress via scavenging the free radicals. In this study, phlorotannin from Padina tetrastromatica brown macroalga was collected from Mandapam, Rameswaram, Tamil Nadu and identified by microscopic observation. The compound was extracted and purified by using column chromatography, thin layer chromatography (TLC) and high-performance liquid chromatography (HPLC). The purified compound showed prominent inhibition of free radicals via reactive oxygen species (ROS) activity in vitro. Further, the compound showed the inhibitory effect of ROS in RAW 264.7 murine macrophage cell line, HeLa human cervical cancer cell line, and SH-SY5Y human neuroblastoma cell line. Further, the effect of the compound on neurotoxicity was carried out in Caenorhabditis elegans as an animal model. The stress-responsive genes daf-16 and sod-1 gene expression studies were performed and results revealed that the aforementioned genes had shown up-regulation in compound treated with acrylamide induced worms. Thus, this compound may prospect for therapeutic applications against the oxidative stress-related complications.

The present research work emphasizes on the study of micro-structure, corrosion and biological behaviour of novel Mg-(0-5)Zn-1Ca/(0-3)hydroxyapatite (HA) composites for future use as biomedical implantation. Microstructures showed a significant grain refinement with increasing Zn content along with HA agglomerates on the surface. Potentiodynamic polarization and electrochemical impedance spectroscopy (EIS) showed that Zn addition in Mg-1Ca alloy is assisting in inhibiting cathodic corrosion while HA addition in Mg-(0-5)Zn-1Ca alloy is increasing anodic corrosion along with Zn. Further, cytotoxicity analysis using direct and indirect contact methods were performed using L-929 cells, which showed that Zn addition (0–3 wt%) slightly increases cell viability and non-toxicity in Mg-1Ca alloy whereas a considerable improvement is observed after HA addition in Mg-Zn-1Ca alloys. Mg-1Zn-1Ca/3HA and Mg-3Zn-1Ca/3HA alloys/composites were observed to have controlled corrosion and non-toxic to L-929 cells.

Marine cyanobacteria Lyngbya sp. has been reported to produce many bioactive secondary metabolites which shows potent anti-oxidant, anti-inflammatory, anti-diabetic and anti-cancer activity. However, several potentials are yet to be unexplored. Hence in this study, ethanolic fraction (EF) of Lyngbya sp. was used to analyse its therapeutic potentials. The extract was collected and analyzed by Fourier-transform infrared spectroscopy and Gas chromatography-mass spectrometry. The anti-oxidant activity and Advanced Glycation End products (AGEs) inhibition by EF was explicitly studied in hyperglycaemic C. elegans as an animal model by live animal imaging and spectrofluorimetry assays. Live imaging and spectrofluorimetry analysis of hyperglycaemic C. elegans by high content screening revealed the decreased fluorescence intensity corresponding to AGE formation in EF treated animals than control. Likewise C. elegans treated with EF had also shown low internal glucose levels in 100 mmol/L and 200 mmol/L hyperglycemic worms, respectively than the hyperglycemic worms 100 mmol/L and 200 mmol/L, respectively. Moreover semi-quantitative RT-PCR studies showed the EF treated nematodes showed up-regulated glod- 4 and daf-16 expressions, while a decrease in daf-2 expression thus proving its role in AGE mitigation and increasing longevity in stress conditions. Anti-inflammatory study was also studied by using daf- 16 gene in C. elegansTJ356 daf16::GFP as an animal model. Thus, the ethanolic fraction of Lyngbya sp. extracts have the therapeutic potential as an inhibitor of AGE formation by modulating stress response gene expression and inflammation by controlling of daf- 16 gene.

L-asparaginase, a therapeutic involved in cancer therapy, from Bacillus tequilensis PV9W (ansA gene) was cloned and over expressed in Escherichia coli BL21 (DE3), achieved the aim of maximizing the yield of the recombinant enzyme (6.02 ± 1.77 IU/mL) within 12 h. The native L-asparaginase of B. tequilensis PV9W was encapsulated using solid lipid particles by hot lipid emulsion method, which is reported for first time in this study. Subsequently, the lipid encapsulated L-asparaginase (LPE) was characterized by SEM, UV-Vis spectroscopy, FT-IR, SDS-PAGE and its thermo stability was also analyzed by TGA. Further characterization of LPE revealed that enzyme was highly stable for 25 days when stored at 25 °C, showed high pH (9) tolerance and longer trypsin half-life (120 min). In addition, the cytotoxic ability of LPE on HeLa cells was highly enhanced compared to the native L-asparaginase from Bacillus tequilensis PV9W. Moreover, better kinetic velocity and lower Km values of LPE aided to detect L-asparagine in cell extracts by Differential Pulse Voltammetry (DPV) method. The LPE preparation also showed least immunogenic reaction when tested on normal macrophage cell lines. This LPE preparation might thus pave way for efficient drug delivery and enhancing the stability of L-asparaginase for its therapeutic applications.

Marine cyanobacteria are renowned for producing bioactive secondary metabolites with great structural diversity via mixed biosynthetic pathways. Lyngbya sp., a marine cyanobacterium, produces many metabolites with anti-inflammatory potentials; nevertheless, its bioactive metabolites exercising providing protection against inflammation has been deciphered inadequate. In this study, the ethanolic fraction of the Lyngbya sp. extract was purified and identified as sodium 10-amino-2-methoxyundecanoate (SAM) using Fourier-transform infrared spectroscopy, nuclear magnetic resonance, and electron spray ionization-mass spectroscopy. SAM showed prominent inhibition of inflammation, which was analyzed by reactive oxygen species generation and nitric oxide (NO) inhibition assay. Furthermore, the anti-inflammatory potentials of SAM were evaluated in lipopolysaccharide (LPS)-induced RAW 264.7 macrophage cell lines by fluorescence-activated cell sorting analysis, which evidenced prominent decrease in COX-2 expression (∼90%) with SAM-treated cells than the control. Subsequently, a semiquantitative real-time polymerase chain reaction analysis also revealed the downregulation of COX-2, iNOS, TNF-α, NF-κß, IL-1α, IL-1ß, IL-4, and IL-6 gene expression in SAM-treated LPS-induced RAW 264.7 cells. To further enhance the delivery of SAM into the cells, it was combined with N-doped graphene quantum dots (N-GQDs) for the anti-inflammatory potentials. It resulted in improved downregulation of COX-2, iNOS, TNF-α, NF-κß, IL-1α, IL-1ß, IL-4, and IL-6 than cells treated with SAM alone. Conclusively, N-GQDs combined with SAM have the effective therapeutic potential as an inhibitor of inflammation by modulating the expression of different cytokine genes.

Cyanobacterial phycocyanin (C-PC) has always been used in therapeutics and nutraceuticals. Herein we report, enhanced C-PC production by Oscillatoria sp. 50A through media optimization using response surface methodology (RSM) with two folds higher C-PC yield (0.072 +/- 0.001mg/mL) in 30 days with optimized media containing 2.5mL/L each of sugar industrial effluent (SE) and tannery effluent (TE) than normal BG-11 medium. Moreover, C-PC was successfully purified to homogeneity and characterized by FT-IR, spectrofluorimetry and MALDI-TOF peptide fingerprinting. The therapeutic efficacy of C-PC was studied invivo in hypercholesterol induced daf-16::GFP C. elegans, which evidenced prominent down-regulation of daf-16 (0.5 +/- 0.2 fold) in C-PC treated obese vs untreated obese worms. In another independent model study, the purified C-PC exerted cytotoxicity in HeLa cells at IC50 value of 77.76 +/- 2.41 g/mL, which induced pro-apoptotic p53 expression, indicating its potential implications as cancer therapeutic agent. Moreover, C-PC does not induce any cytotoxicity or immune response on normal RAW 264.7 macrophage cells. Thus, the cost-efficient way of hyper-production of C-PC from cyanobacteria Oscillatoria sp. 50A can be achieved using agro-industrial wastes such as SE and TE for versatile therapeutic applications in treatment of obesity and/or cancer.

Agricultural wastes such as the peels of onion and garlic were used as a supplement along with l-asparagine for the very first time to produce increased yield of l-asparaginase by Pseudomonas plecoglossicida RS1. Statistical optimization strategies such as response surface methodology were used to generate a medium composition containing extracts of 0.9 (v/v) of garlic peel waste and 0.5% (v/v) onion peel waste along with 0.2% (w/w) l-asparagine, which yielded a twofold increase in the enzyme activity compared to the unsupplemented minimal (M-9) medium. The presence of l-asparagine content in the peel extract was confirmed by high-performance liquid chromatography. Further, l-asparaginase was purified to homogeneity, and identity was confirmed by matrix-assisted laser desorption ionization time-of-flight analysis. The application of the purified l-asparaginase as a therapeutic was studied in HeLa cells which showed a p53-mediated G2 cell cycle arrest. Moreover, the purified l-asparaginase showed effective acrylamide mitigation in vitro, at 6 IU, and its effective degradation was also demonstrated by the effect on chemotactic index of Caenorhabditis elegans and the restoration of the cognitive abilities of C. elegans which was coexposed to acrylamide and l-asparaginase compared to that exposed to acrylamide alone. Thus, l-asparaginase, with multipotent applications, was produced by effective waste utilization for economical commercial production.

Here we have demonstrated a novel single step technique of synthesis of highly fluorescent carbon nanoparticles (CNPs) from broth constituent and in vivo bioimaging of Caenorhabditis elegans (C. elegans) with the synthesized CNPs has been presented. The synthesized CNPs has been characterized by the UV-visible (UV-Vis) absorption spectroscopy, transmission electron microscopy (TEM) and Raman studies. The sp 2 cluster size of the synthesized samples has been determined from the measured Raman spectra by fitting it with the theoretical skew Lorentzian (Breit-Wigner- Fano (BWF)) line shape. The synthesised materials are showing excitation wavelength dependent tunable photoluminescence (PL) emission characteristics with a high quantum yield (QY) of 3 % at a very low concentration of CNPs. A remarkable increase in the intensity of PL emission from 16 % to 39 % in C. elegans has also been observed when the feeding concentration of CNPs to C. elegans is increased from 0.025 % to 0.1 % (w/v). The non-toxicity and water solubility of the synthesized material makes it ideal candidate for bioimaging.

Glutaminase freel-asparaginase from a marine isolateBacillus tequilensisPV9W: production, purification, characterization and its biological applications.

Correction for ‘Hemocompatible glutaminase free l-asparaginase from marine Bacillus tequilensis PV9W with anticancer potential modulating p53 expression’ by Ganeshan Shakambari et al., RSC Adv., 2016, 6, 25943–25951.