Corroborative studies on chain packing characteristics of biological medium-chain-length poly-3-hydroxyalkanoates with different monomeric composition.

Medium-chain-length poly-3-hydroxyalkanoates (mcl-PHAs) with varied monomeric compositions were biosynthesized by producer bacteria fed with different fatty acids as carbon source. Octanoic-, lauric-, stearic-, and oleic acids were used to produce four types of mcl-PHAs viz. PHA-OC, PHA-LA, PHA-ST, and PHA-OL, respectively. The mcl-PHAs as film-casted preparations exhibit distinct traits e.g., PHA-OC and PHA-ST films are less flexible than PHA-LA while PHA-OL is a sticky, glue-like material; PHA-ST is opaque whereas PHA-OC, PHA-LA, and PHA-OL displayed transparent layers. The observation is attributed to polymer chain packing and side chain crystallization. A structure-property investigation of these biopolymers was carried out employing different spectroscopic and microscopic analyses in addition to thermal analyses. Comparative analyses of the results were applied in the interpretation and discussion of structure-property relationship.

Non-lamellar lyotropic liquid crystalline nanoparticles as nanocarriers for enhanced drug encapsulation of atorvastatin calcium and proanthocyanidins.

Atorvastatin calcium (ATV) and proanthocyanidins (PAC) have a strong antioxidant activity, that can benefit to reduce the atherosclerotic plaque progression. Unfortunately, the bioavailability of ATV is greatly reduced due to its limited drug solubility while the PAC drug is unstable upon exposure to the atmospheric oxygen. Herein, the lyotropic liquid crystalline nanoparticles (LLCNPs) constructed by a binary mixture of soy phosphatidylcholine (SPC) and citric acid ester of monoglyceride (citrem) at different weight ratios were used to encapsulate the hydrophobic ATV and hydrophilic PAC. The LLCNPs were further characterized by small-angle X-ray scattering and dynamic light scattering. Depending on the lipid composition, the systems have a size range of 140-190 nm and were able to encapsulate both drugs in the range of 90-100%. Upon increasing the citrem content of drug-loaded LLCNPs, the hexosomes (H2) was completely transformed to an emulsified inverse micellar (L2). The optimum encapsulation efficiency (EE) of ATV and PAC were obtained in citrem/SPC weight ratio 4:1 (L2) and 1:1 (H2), respectively. There was a substantial change in the mean size and PDI of the nanoparticles upon 30 days of storage with the ATV-loaded LLCNPs exhibiting greater colloidal instability than PAC-loaded LLCNPs. The biphasic released pattern (burst released at the initial stage followed by the sustained released at the later stage) was perceived in ATV formulation, while the burst drug released pattern was observed in PAC formulations that could be attributed by its internal H2 structure. Interestingly, the cytokine studies showed that the PAC-LLCNPs promisingly up regulate the expressions of tumor necrosis factor-alpha (TNF-α) better than the drug-free and ATV-loaded LLCNPs samples. The structural tunability of citrem/SPC nanoparticles and their effect on physicochemical characteristic, biological activities and potential as an alternative drug delivery platform in the treatment of atherosclerosis are discussed.

Coencapsulation of Gemcitabine and Thymoquinone in Citrem-Phosphatidylcholine Hexosome Nanocarriers Improves In Vitro Cellular Uptake in Breast Cancer Cells.

Lyotropic liquid crystalline nanoassemblies (LLCNs) are internally self-assembled (ISA)-somes formed by amphiphilic molecules in a mixture comprising a lipid, stabilizer, and/or surfactant and aqueous media/dispersant. LLCNs are unique nanoassemblies with versatile applications in a wide range of biomedical functions. However, they comprise a nanosystem that is yet to be fully explored for targeted systemic treatment of breast cancer. In this study, LLCNs proposed for gemcitabine and thymoquinone (Gem-TQ) co-delivery were prepared from soy phosphatidylcholine (SPC), phytantriol (PHYT), or glycerol monostearate (MYVR) in optimized ratios containing a component of citric and fatty acid ester-based emulsifier (Grinsted citrem) or a triblock copolymer, Pluronic F127 (F127). Hydrodynamic particle sizes determined were below 400 nm (ranged between 96 and 365 nm), and the series of nanoformulations displayed negative surface charge. Nonlamellar phases identified by small-angle X-ray scattering (SAXS) profiles comprise the hexagonal, cubic, and micellar phases. In addition, high entrapment efficiency that accounted for 98.3 ± 0.1% of Gem and 99.5 ± 0.1% of TQ encapsulated was demonstrated by the coloaded nanocarrier system, SPC/citrem/Gem-TQ hexosomes. Low cytotoxicity of SPC-citrem hexosomes was demonstrated in MCF10A cells consistent with hemo- and biocompatibility observed in zebrafish (Danio rerio) embryos for up to 96 h postfertilization (hpf). SPC/citrem/Gem-TQ hexosomes demonstrated IC50 of 24.7 ± 4.2 µM in MCF7 breast cancer cells following a 24 h treatment period with the moderately synergistic interaction between Gem and TQ retained (CI = 0.84). Taken together, biocompatible SPC/citrem/Gem-TQ hexosomes can be further developed as a multifunctional therapeutic nanodelivery approach, plausible for targeting breast cancer cells by incorporation of targeting ligands.

Mapping glycine uptake and its metabolic conversion to glutathione in mouse mammary tumors using functional mass spectrometry imaging.

Although glutathione plays a key role in cancer cell viability and therapy response there is no clear trend in relating the level of this antioxidant to clinical stage, histological grade, or therapy response in patient tumors. The likely reason is that static levels of glutathione are not a good indicator of how a tissue deals with oxidative stress. A better indicator is the functional capacity of the tissue to maintain glutathione levels in response to this stress. However, there are few methods to assess glutathione metabolic function in tissue. We have developed a novel functional mass spectrometry imaging (fMSI) method that can map the variations in the conversion of glycine to glutathione metabolic activity across tumor tissue sections by tracking the fate of three glycine isotopologues administered in a timed sequence to tumor-bearing anesthetized mice. This fMSI method generates multiple time point kinetic data for substrate uptake and glutathione production from each spatial location in the tissue. As expected, the fMSI data shows glutathione metabolic activity varies across the murine 4T1 mammary tumor. Although glutathione levels are highest at the tumor periphery there are regions of high content but low metabolic activity. The timed infusion method also detects variations in delivery of the glycine isotopologues thereby providing a measure of tissue perfusion, including evidence of intermittent perfusion, that contributes to the observed differences in metabolic activity. We believe this new approach will be an asset to linking molecular content to tissue function.

Multiple Infusion Start Time Mass Spectrometry Imaging of Dynamic SIL-Glutathione Biosynthesis Using Infrared Matrix-Assisted Laser Desorption Electrospray Ionization.

Due to the high association of glutathione metabolism perturbation with a variety of disease states, there is a dire need for analytical techniques to study glutathione kinetics. Additionally, the elucidation of microenvironmental effects on changes in glutathione metabolism would significantly improve our understanding of the role of glutathione in disease. We therefore present a study combining a multiple infusion start time protocol, stable isotope labeling technology, infrared matrix-assisted laser desorption electrospray ionization, and high-resolution accurate mass-mass spectrometry imaging to study spatial changes in glutathione kinetics across in sectioned mouse liver tissues. After injecting a mouse with the isotopologues [2-13C,15N]-glycine, [1,2-13C2]-glycine, and [1,2-13C2,15N]-glycine at three different time points, we were able to fully resolve and spatially map their metabolism into three isotopologues of glutathione and calculate their isotopic enrichment in glutathione. We created a tool in the open-source mass spectrometry imaging software MSiReader to accurately compute the percent isotope enrichment (PIE) of these labels in glutathione and visualize them in heat-maps of the tissue sections. In areas of high flux, we found that each label enriched an approximate median of 1.6%, 1.8%, and 1.5%, respectively, of the glutathione product pool measured in each voxel. This method may be adapted to study the heterogeneity of glutathione flux in diseased versus healthy tissues.

Workplace mistreatment and mental health in female surgeons in Pakistan.

BACKGROUND: Despite workplace mistreatment, which includes harassment, bullying and gender discrimination(GD)/bias, being serious problems for female surgeons, there are limited data from lower-middle-income countries like Pakistan. This study explored harassment and GD/bias experienced by female surgeons in Pakistan, and the effects of these experiences on mental health and well-being. METHODS: A nationwide survey was conducted between July and September 2019 in collaboration with the Association of Women Surgeons of Pakistan, an organization consisting of female surgeons and trainees in Pakistan. An anonymous online survey was emailed directly, disseminated via social media platforms (such as Facebook, Twitter and Instagram), and sent to surgical programmes in Pakistan. RESULTS: A total of 146 women surgeons responded to the survey; 67.1 per cent were trainees and the rest attending surgeons. Overall, 57.5 per cent of surgeons reported experiencing harassment, most common being verbal (64.0 per cent) and mental (45.9 per cent), but this mostly went unreported (91.5 per cent). On multivariable analysis adjusted for age and specialty, workplace harassment (odds ratio 2.02 (95 per cent c.i. 1.09 to 4.45)) and bullying (odds ratio 5.14 (95 per cent c.i. 2.00-13.17)) were significantly associated with severe self-perceived burnout, while having a support system was protective against feelings of depression (odds ratio 0.35 (95 per cent c.i. 0.16 to 0.74)). The overwhelming majority (91.3 per cent) believed that more institutional support groups were needed to help surgeons with stress reduction (78.8 per cent), receiving mentorship (74.7 per cent) and work-life balance (67.8 per cent). CONCLUSION: Workplace mistreatment, in particular harassment and bullying, has a damaging impact on the mental well-being of female surgeons, particularly trainees. The absence of support groups in Pakistan should be urgently addressed so that surgeons, especially trainees, may cope better with potentially harmful workplace stressors.

Probing n-Octyl α-d-Glycosides Using Deuterated Water in the Lyotropic Phase by Deuterium NMR.

The lyotropic phase behavior of four common and easily accessible glycosides, n-octyl α-d-glycosides, namely, α-Glc-OC8, α-Man-OC8, α-Gal-OC8, and α-Xyl-OC8, was investigated. The presence of normal hexagonal (HI), bicontinuous cubic (VI), and lamellar (Lα) phases in α-Glc-OC8 and α-Man-OC8 including their phase diagrams in water reported previously was verified by deuterium nuclear magnetic resonance (2H NMR), via monitoring the D2O spectra. Additionally, the partial binary phase diagrams and the liquid crystal structures formed by α-Gal-OC8 and α-Xyl-OC8 in D2O were constructed and confirmed using small- and wide-angle X-ray scattering and 2H NMR. The average number of bound water molecules (nb) per headgroup in the Lα phase was determined by the systematic measurement of the quadrupolar splitting of D2O over a wide range of molar ratio values (glycoside/D2O), especially at high glucoside composition. The number of bound water molecules bound to the headgroup was found to be around 1.5-2.0 for glucoside, mannoside, and galactoside, all of which possesses four OH groups. In the case of xyloside, which has only three OH groups, the bound water content is ∼2.0. Our findings confirmed that the bound water content of all n-octyl α-d-glycosides studied is lower compared to the number of possible hydrogen bonding sites possibly due to the fact that most of the OH groups are involved in intralayer interaction that holds the lipid assembly together.

Lymph node ratio as a prognostic marker of oral tongue squamous cell carcinoma: a cohort study.

INTRODUCTION: Lymph node metastasis is a poor prognostic indicator and is well established in tongue squamous cell carcinoma. Based on the current staging system, accurate risk stratification is difficult. There is thus a need to evaluate an alternate method for predicting recurrence and survival. The objective of the study was to evaluate lymph node ratio as a prognostic marker as compared with N-staging for tongue squamous cell carcinoma. MATERIALS AND METHODS: We conducted a retrospective cohort study with 56 patients with a lymph node ratio greater than 0.012 (exposed) and 74 patients with a lymph node ratio less than 0.012 (unexposed). Overall five-year survival and disease-free survival were assessed. The Cox proportional hazard model was used to analyse lymph node ratio as a predictor of outcome, together with other covariates. RESULTS: A total of 130 patients were included in the study. Patients with lymph node ratio greater than 0.012 had a poor overall five-year (mean survival time 52.1 months vs 38.1 months) and disease-free survival (mean survival time 53.6 months vs 39.2 months). The hazard of death among patients with a lymph node ratio greater than 0.012 was 3.24 times higher than the hazard of death among patients with a lymph node ratio less than 0.012 (95% confidence interval 1.82-5.77). DISCUSSION: Lymph node ratio is a superior prognostic marker compared with the currently used American Joint Committee on Cancer N-staging. Our findings also suggest that the margin status (involved) of the primary tumour resection adversely affects prognosis.

Flow-Encoded Oxygen Control to Track the Time-Dependence of Molecular Changes Induced by Static or Cycling Hypoxia.

Detecting the effects of low oxygen on cell function is often dependent on monitoring the expression of a number of hypoxia markers. The time dependence of the appearance and stability of these markers varies between cell lines. Assessing cellular marker dynamics is also critical to determining how quickly cells respond to transient changes in oxygen levels that occurs with cycling hypoxia. We fabricated a manifold designed to use flow-encoding to produce sequential changes in gas mixtures delivered to a permeable-bottom 96-well plate. We show how this manifold and plate design can be used to expose cells to either static or cycling hypoxic conditions for eight different time periods thereby facilitating the study of the time-response of cells to altered oxygen environments. Using this device, we monitored the time-dependence of molecular changes in human PANC-1 pancreatic carcinoma and Caco-2 colon adenocarcinoma cells exposed to increasing periods of static or cycling hypoxia. Using immunohistochemistry, both cell lines show detectable levels of the marker protein hypoxia-inducible factor-1α (HIF-1α) after 3 h of exposure to static hypoxia. Cycling hypoxia increased the expression level of HIF-1α compared to static hypoxia. Both static and cycling hypoxia also increased glucose uptake and aldehyde dehydrogenase activity. This new device offers a facile screening approach to determine the kinetics of cellular alterations under varying oxygen conditions.

Optical Properties of Azo-Benzothiazole Side Chain Liquid Crystalline Polymers: Effect of Solvents, Substituents and Temperatures.

The optical properties of a series of side chain liquid crystalline polymers (P1-P3) containing azo-benzothiazole mesogen with different terminal substituents (-H, -CH3 and -OCH2CH3) in four organic solvents of varying polarity have been investigated by absorption and fluorescence spectral analysis. Solvatochromic studies of P1-P3 did not show any regular variation on the absorption and emission intensities with changing the polarity of solvent. Theoretical studies were performed based on different solvent correlation methods such as Dimroth-Reichardt and Kamlet-Taft methods to investigate the solute-solvent interactions. Both absorption and emission maxima of investigated polymers were bathochromically shifted with the replacement of sixth position hydrogen atom by electron donating groups in benzothiazole moiety. The emission intensities of the studied polymers showed decreasing trend with increasing temperature.

Evidence of Increased Hydrophobicity and Dynamics inside the Tail Region of Glycolipid Self-Assemblies Using 2-n-Alkyl-Pyrene Derivatives to Probe Different Locations.

New designer biofluorophores are being increasingly used in the investigation of complex cellular processes. In this study, we utilized new derivatives of pyrene (Py), i.e., 2-n-alkyl-pyrenes (Py-C4 and Py-C8), in order to probe different regions inside the hydrophobic tail of n-dodecyl ß-d-maltoside (ßMal-C12) in two different phases (cubic ↔ lamellar). Although the sensitivity to the local environment is reduced compared to that of Py, attaching C4 and C8 at the 2-position of Py can provide a possible means to probe the local hydrophobicity in different parts of the tail region. The absence of excimer fluorescence and the ratio of the vibronic fluorescence peak intensities (I1/I3) in a lipid environment indicate the existence of Py as monomers in the hydrophobic region, similar to hydrophobic solvation, yet close to the headgroup region. When Py is replaced by Py-C4 and Py-C8, there is a small increase in hydrophobicity (reduction in I1/I3) as the Py moiety is pulled deeper inside the tail region of both cubic and lamellar phases. The larger space of the tail region in the lamellar phase is reflected as more local hydrophobicity measured by the probes which can penetrate deep inside, whereas the curved structure of the cubic phase limits the available space for the probes. Three fluorescence lifetime components were measured in lipid, indicating the heterogeneous nature of the hydrophobic region. In the lamellar phase, a large reduction in the average lifetime value, led by the long decay component, was measured for Py-C4 (reduction by 25%) and Py-C8 (45%) compared to that of the parent Py. This observation suggests the presence of a mechanism of interaction more collisional than static between the Py moiety and the tail region of the bilayer unit due to the ample space provided by the lamellar phase as the probe is buried deeper inside the hydrophobic region. A much smaller effect was observed in the cubic phase and was correlated with the tight environment around the probes, which stems from the increased curvature of the cubic phase. The current results provide a deeper understanding of the hydrophobic region during phase transition of lipid self-assembly which is important for better control during the process of membrane-protein crystallization.

Mixing and delivery of multiple controlled oxygen environments to a single multiwell culture plate.

Precise oxygen control is critical to evaluating cell growth, molecular content, and stress response in cultured cells. We have designed, fabricated, and characterized a 96-well plate-based device that is capable of delivering eight static or dynamically changing oxygen environments to different rows on a single plate. The device incorporates a gas-mixing tree that combines two input gases to generate the eight gas mixtures that supply each row of the plate with a different gas atmosphere via a removable manifold. Using air and nitrogen as feed gases, a single 96-well plate can culture cells in applied gas atmospheres with Po2 levels ranging from 1 to 135 mmHg. Human cancer cell lines MCF-7, PANC-1, and Caco-2 were grown on a single plate under this range of oxygen levels. Only cells grown in wells exposed to Po2 ≤37 mmHg express the endogenous hypoxia markers hypoxia-inducible factor-1α and carbonic anhydrase IX. This design is amenable to multiwell plate-based molecular assays or drug dose-response studies in static or cycling hypoxia conditions.

Self-Assembly, Thermotropic, and Lyotropic Phase Behavior of Guerbet Branched-Chain Maltosides.

Five synthetic ß-d-maltosides derived from Guerbet branched alcohols, whose total hydrocarbon chain length ranged from C8 to C24, were synthesized to a high anomeric purity, and their thermal properties, liquid-crystalline phases, and structures were characterized using differential scanning calorimetry, optical polarizing microscopy, and small-angle X-ray scattering. Thermal investigations of all anhydrous Guerbet maltosides showed that they do not form solid crystals but undergo a glass transition upon temperature change in the range of 35-53 °C. The glassy crystalline structure turns into the liquid-crystalline structure upon heating or addition of water. In thermotropic studies, the lamellar phase formation is prominent in shorter-chain-length analogues, whereas the longer-chain compounds exhibit a more frustrated form of self-assembly in the formation of a metastable state, polymorphism, and inverse bicontinuous cubic structure ( Ia3 d). The excess water conditions show that the phase formation is dominated by the lamellar phase for the longer-chain compounds. Normal micellar solution was observed in the shortest-chain-length maltosides because of the enlargement of hydrated maltose headgroups. The self-assembly of both dry and fully hydrated Guerbet maltosides, which exhibited glass-forming abilities and showed surface activity and also the ability to act as membrane-stabilizing compounds, makes them ideal candidates for practical use in industry as well as biomedical research.

Dry Thermotropic Glycolipid Self-Assembly:A Review.

Also recognized as carbohydrate liquid crystals, glycolipids are amphiphiles whose basic unit comprises of a sugar group attached to an alkyl chain. Glycolipids are amphitropic, which means these materials form liquid crystal self-assemblies when dry (thermotropic) as well as when dissolved in solvents (lyotropic/surfactants) such as water. Many glycolipids are also naturally derived since these can be found in cell membranes. Their membrane and surfactant functions are largely understood through their lyotropic properties. While glycolipids are expected to play major roles as eco-friendly surfactants in the global surfactant market, their usefulness as thermotropic liquid crystal material is, to date, unknown, due to relatively lack of research performed and data reported in the literature. Understandably since glycolipids are hygroscopic with many hydroxy groups, removing the last trace water is very challenging. In recent time, with careful lyophilization and more consistent characterization technique, some researchers have attempted serious studies into "dry" or anhydrous glycolipids. Motivated by possible developments of novel thermotropic applications, some results from these studies also provide surprising new understanding to support conventional wisdom of the lyotropic systems. Here we review the dry state of glycosides, a family of glycolipids whose sugar headgroup is linked to the lipid chain via a glycosidic oxygen linker. The structure property relationship of both linear and anhydrous Guerbet glycosides will be examined. In particular, how the variation of sugar stereochemistry (e.g. anomer vs. epimer), the chain length and chain branching affect the formation of thermotropic liquid crystals phases, which not only located under equilibrium but also far from equilibrium conditions (glassy phase) are scrutinized. The dry glycolipid assembly has been subjected to electric and magnetic fields and the results show interesting behaviors including a possible transient current generation.

Significance of immunohistochemical overexpression of cyclooxygenase-2 in overall and disease-free survival of oral squamous cell carcinoma patients.

OBJECTIVE: In Pakistan, oral cancer ranks as the most common malignancy in males and the second most common malignancy in females. Cyclooxygenase-2 has been explored as an agent of carcinogenesis in oral and other neoplasms. This study aimed to observe the expression of cyclooxygenase-2 in oral squamous cell carcinoma, and to correlate the expression with patients' clinical features and overall and disease-free survival. METHODS: Immunohistochemistry for cyclooxygenase-2 was performed on a total of 100 oral squamous cell carcinoma formalin-fixed, paraffin-embedded blocks. Expression was correlated with patients' clinicopathological variables and overall and disease-free survival. RESULTS: Cyclooxygenase-2 was overexpressed in 55 per cent of oral squamous cell carcinoma patients. Overexpression was correlated with overall survival (p = 0.013) and disease-free survival (p = 0.001) on univariate analysis. However, on multivariate analysis, cyclooxygenase-2 was associated with only disease-free survival (p = 0.044) and not overall survival (p = 0.208). CONCLUSION: Expression of cyclooxygenase-2 is associated with poorer overall survival and higher rates of recurrence in oral squamous cell carcinoma patients.

New Insight into the Origin of the Red/Near-Infrared Intense Fluorescence of a Crystalline 2-Hydroxychalcone Derivative: A Comprehensive Picture from the Excited-State Femtosecond Dynamics.

Fluorescence upconversion and transient absorption techniques are used to explain the source of the intense red/near-infrared emission of crystalline 4-dimethylamino-2'-hydroxychalcone. We found that the initially excited enol form undergoes tautomerization in 3 ps to form the keto tautomer. The latter is stable in the ground state as a consequence of J-type aggregation in the crystal packing and is manifested in an absorption peak at 550 nm that spectrally overlaps with the short-lived enol emission, leading to self-reabsorption and adding a factor to the complete depletion of the enol emission. Relaxation of the keto tautomer takes place in the form of intense fluorescence (600-750 nm) with 1.7 ns lifetime. The different spectroscopy in solution is due to vibrational cooling (300 fs), followed by solvation dynamics (5 ps in methanol) and twisting of the hydroxyphenyl ring (16 ps), before relaxation of the enol tautomer in the form of weak green fluorescence with 350 ps lifetime.

Swelling of Bicontinuous Cubic Phases in Guerbet Glycolipid: Effects of Additives.

Inverse bicontinuous cubic phases of lyotropic liquid crystal self-assembly have received much attention in biomedical, biosensing, and nanotechnology applications. An Ia3d bicontinuous cubic based on the gyroid G-surface can be formed by the Guerbet synthetic glucolipid 2-hexyl-decyl-ß-d-glucopyranoside (ß-Glc-OC6C10) in excess water. The small water channel diameter of this cubic phase could provide nanoscale constraints in encapsulation of large molecules and crystallization of membrane proteins, hence stresses the importance of water channel tuning ability. This work investigates the swelling behavior of lyotropic self-assembly of ß-Glc-OC6C10 which could be controlled and modulated by different surfactants as a hydration-modulating agent. Our results demonstrate that addition of nonionic glycolipid octyl-ß-d-glucopyranoside (ß-Glc-OC8) at 20 and 25 mol % gives the largest attainable cubic water channel diameter of ca. 62 Å, and formation of coacervates which may be attributed to a sponge phase were seen at 20 mol % octyl-ß-d-maltopyranoside (ß-Mal-OC8). Swelling of the cubic water channel can also be attained in charged surfactant-doped systems dioctyl sodium sulfosuccinate (AOT) and hexadecyltrimethylammonium bromide (CTAB), of which phase transition occurred from cubic to a lamellar phase. Destabilization of the cubic phase to an inverse hexagonal phase was observed when a high amount of charged lecithin (LEC) and stearylamine (SA) was added to the lipid self-assembly.

Molecular dynamics of anhydrous glycolipid self-assembly in lamellar and hexagonal phases.

The molecular dynamics of a synthetic branched chain glycolipid, 2-decyl-tetradecyl-ß-d-maltoside (C14-10G2), in the dry assemblage of smectic and columnar liquid crystal phases has been studied by dielectric spectroscopy as a function of frequency and temperature during the cooling process. Strong relaxation modes were observed corresponding to the tilted smectic and columnar phases, respectively. At low frequency (∼900 Hz to 1 kHz) in the smectic phase, Process I* was observed due to the tilted sugar bilayer structure. The process continued in the columnar phase (Process I) with an abrupt dynamic change due to phase transition in the frequency range of ∼1.3 kHz to 22 kHz. An additional process (Process II) was observed in the columnar phase with a broader relaxation in the frequency range of ∼10 Hz to 1 kHz. A bias field dependence study was performed in the columnar phase and we found that the relaxation strength rapidly decreased with increased applied dc bias field. This relaxation originates from a collective motion of polar groups within the columns. The results of dielectric spectroscopy were supported by a molecular dynamics simulation study to identify the origin of the relaxation processes, which could be related to the chirality and hydrogen bonds of the sugar lipid.

Subcutaneous administration of bovine superoxide dismutase protects lungs from radiation-induced lung injury.

BACKGROUND: The objective of the present study was to determine whether single administration of the antioxidant enzyme bovine superoxide dismutase (bSOD) after radiation therapy (RT) mitigates development of pulmonary toxicity in rats. METHODS: Female F344 rats (n = 60) were divided among six experimental groups: (1) RT, single dose of 21 Gy to the right hemithorax; (2) RT + 5 mg/kg bSOD; (3) RT + 15 mg/kg bSOD; (4) No RT; (5) sham RT + 5 mg/kg bSOD; and (6) sham RT + 15 mg/kg bSOD. A single subcutaneous injection of bSOD (5 or 15 mg/kg) was administered 24 h post-radiation. The effects of bSOD on radiation-induced lung injury were assessed by measurement of body weight, breathing frequency, and histopathological changes. Immunohistochemistry was used to evaluate oxidative stress (8-OHdG(+), NOX4(+), nitrotyrosine(+), and 4HNE(+) cells), macrophage activation (ED1(+)), and expression of profibrotic transforming growth factor-ß or TGF-ß in irradiated tissue. RESULTS: Radiation led to an increase in all the evaluated parameters. Treatment with 15 mg/kg bSOD significantly decreased levels of all the evaluated parameters including tissue damage and breathing frequency starting 6 weeks post-radiation. Animals treated with 5 mg/kg bSOD trended toward a suppression of radiation-induced lung damage but did not reach statistical significance. CONCLUSIONS: The single application of bSOD (15 mg/kg) ameliorates radiation-induced lung injury through suppression of reactive oxygen species/reactive nitrogen species or ROS/RNS-dependent tissue damage.

Detecting local heterogeneity and ionization ability in the head group region of different lipidic phases using modified fluorescent probes.

Local heterogeneity in lipid self-assembly is important for executing the cellular membrane functions. In this work, we chemically modified 2-(2'-hydroxyphenyl)benzoxazole (HBO) and attached a C8 alkyl chain in two different locations to probe the microscopic environment of four lipidic phases of dodecyl ß-maltoside. The fluorescence change in HBO and the new probes (HBO-1 and HBO-2) shows that in all phases (micellar, hexagonal, cubic and lamellar) three HBO tautomeric species (solvated syn-enol, anionic, and closed syn-keto) are stable. The formation of multi tautomers reflects the heterogeneity of the lipidic phases. The results indicate that HBO and HBO-1 reside in a similar location within the head group region, whereas HBO-2 is slightly pushed away from the sugar-dominated area. The stability of the solvated syn-enol tautomer is due to the formation of a hydrogen bond between the OH group of the HBO moiety and an adjacent oxygen atom of a sugar unit. The detected HBO anions was proposed to be a consequence of this solvation effect where a hydrogen ion abstraction by the sugar units is enhanced. Our results point to a degree of local heterogeneity and ionization ability in the head group region as a consequence of the sugar amphoterism.