Exploring the Physical Properties of Lipid Membranes with Polyhydroxy Oxanorbornane Head Group Using NBD-Conjugated and DPH Fluorescent Probes.

The present study focuses on exploring the physical properties of lipid membranes based on the polyhydroxy oxanorbornane (PH-ONB) headgroup, designed as synthetic analogues of naturally occurring archaeal lipid membranes. Specifically, we study two variants of PH-ONB headgroup-based lipids differing in the number of hydroxy groups present in the headgroup, with one having two hydroxy groups (ONB-2OH) and the other having three (ONB-3OH). These lipids form stable bilayer membranes. The study begins with a comprehensive analysis of the fluorescence characteristics of nitrobenzoxadiazole (NBD)-tagged ONB-based lipids in different solvent environments and within a model lipid membrane 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC). Subsequently, the physical properties of the ONB-based membranes were examined by using an NBD-tagged ONB-based probe and a commonly used extrinsic 1,6-diphenyl-1,3,5-hexatriene (DPH) fluorescent probe. The steady-state and time-resolved fluorescence properties of the NBD-tagged ONB-based probe and DPH were used to compare the physical properties of the ONB-based membranes, including polarity, fluidity, phase transition, order, hydration, location, heterogeneity, and rotational diffusion. The solid gel to liquid crystalline phase transition temperatures of ONB-2OH and ONB-3OH lipid membranes are found to be (68 ± 1) °C and (74 ± 1) °C, respectively. The variation in organization (size), fluidity, and phase transition temperature of ONB-based lipid membranes is explained by the extent of hydrogen bonding interactions between lipid head groups. ONB-based membranes exhibit characteristics similar to those of phospholipid membranes and possess a notably high phase transition temperature. These properties make them a promising and cost-effective synthetic alternative to archaeal lipid membranes with a wide range of potential applications.

Impact of community health workers on improving identification and primary care of hypertension among the urban poor - findings from Chhattisgarh state of India.

BACKGROUND: Hypertension is a major health problem globally and in India. Around 60% of people with hypertension in India are not aware that they have the condition. Less than 30% of individuals with hypertension are on treatment. Existing studies have indicated that community health workers (CHWs) can play a useful role in expanding the care for hypertension. Evaluations are needed to study the impact when an intervention is implemented by the government in its existing large-scale CHW programme to improve the identification, regular follow-up and medication adherence for hypertension. METHODS: Chhattisgarh state implemented a pilot intervention to improve screening and follow-up for hypertension by equipping Mitanin-CHWs to measure blood pressure (BP). The study design involved an intervention-group and a comparison-group of urban slum population. The survey covered 5974 individuals (30-79 years age) in intervention-group and 5131 in comparison-group. Multivariate analysis was conducted to find out the effect of intervention on the desired outcomes. RESULTS: In intervention-group, 80.2% of the individuals (30-79 years age) had been screened for hypertension whereas the proportion was 37.9% in comparison-group. For 47.0% of individuals in intervention-group, Mitanin CHW was the provider who measured BP for the first time. Around 16.3% of individuals in intervention-group and 9.5% in comparison-group had been diagnosed with hypertension. Around 85.9% of hypertension cases in intervention-group and 77.0% in comparison-group were on treatment. BP had been measured in preceding 30 days for 81.8% of hypertension-cases in intervention-group and 64.3% in comparison-group. Around 70.3% of hypertension-cases in intervention-group and 55.1% in comparison-group had taken their complete medication for last seven days. Multivariate analysis showed that CHW intervention was associated significantly with improvements in all the desired outcomes. CONCLUSION: Equipping the CHWs to measure BP was effective in increasing the screening and identification of hypertension, regular measurement of BP of individuals with hypertension and the adherence to medication. This shows the potential if the one-million strong work-force of Accredited-Social-Health-Activists (ASHA) CHWs in India gets equipped for this role. Governments need to provide a stronger policy push to get this materialised.

Photophysical Behavior of Plant Flavonols Galangin, Kaempferol, Quercetin, and Myricetin in Homogeneous Media and the DMPC Model Membrane: Unveiling the Influence of the B-Ring Hydroxylation of Flavonols.

Flavonols have been studied extensively because of their interesting biological activities and excited-state intramolecular proton transfer (ESIPT) behavior. Galangin, kaempferol, quercetin, and myricetin are structurally related flavonols that differ only in the number of B-ring hydroxyl substituents. In this work, we have carried out a detailed study on the photophysical behavior of these structurally related flavonols in various solvents and a 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) small unilamellar vesicles (SUVs) model membrane. We observed that these flavonols exist in different forms in the ground and excited states depending on the nature of the solvent. The weak intrinsic fluorescence of these flavonols gets enhanced in hydrogen-bond-accepting and alcoholic solvents. The phototautomer fluorescence intensity of these flavonols increases significantly in the DMPC membrane compared to water, suggesting ESIPT activation via binding interaction between flavonols and the membrane. According to our findings, both the number of B-ring hydroxy groups and membrane fluidity affect the flavonol binding with the membrane. The steady-state fluorescence intensity, steady-state anisotropy, fluorescence lifetime, and fluorescence anisotropy decay of flavonols were sensitive towards the temperature-induced DMPC membrane phase change. A quenching study has been performed to investigate the location and distribution of flavonols in the DMPC SUVs. Moreover, the antioxidant potential of flavonols in DMPC SUVs has been examined using the DPPH scavenging method. Our results reveal that the B-ring hydroxy groups significantly affect the photophysics, binding affinity, location, distribution, and DPPH scavenging activity of polyhydroxy-flavonols in the DMPC SUVs.

Interaction of Dopamine with Zwitterionic DMPC and Anionic DMPS Multilamellar Vesicle Membranes.

Dopamine (DA), a naturally occurring neurotransmitter, plays a crucial role in the function of the mammalian nervous system. DA-lipid-membrane interaction is inevitable during the neurotransmission process. In this report, we have studied the interaction of DA with anionic 1,2-dimyristoyl-sn-glycero-3-phospho-l-serine (DMPS), neutral (zwitterionic) 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), and synaptic membrane-mimicking mixed DMPC/DMPS (3:1 molar ratio) model multilamellar vesicle (MLV) membranes. Differential scanning calorimetry (DSC) studies suggest a strong specific interaction of DA with the anionic DMPS membrane, a weak interaction with the zwitterionic DMPC membrane, and a moderate interaction with the mixed DMPC/DMPS (3:1) membrane. The intrinsic fluorescence of DA was used as a new approach to gain a molecular-level understanding of DA-lipid-membrane interaction. Toward this end, a detailed photophysical study of DA, including its steady-state fluorescence anisotropy and fluorescence lifetime, was undertaken for the first time. The partition coefficient, location, and distribution of DA in the DMPS and DMPC model membranes were studied by employing intrinsic fluorescence. The effect of DA on the phase transition of the model membranes was also examined using the intrinsic fluorescence of DA. Zeta potential studies suggest a strong electrostatic interaction of DA with the anionic DMPS membrane and a nonspecific, relatively weak interaction of DA with the zwitterionic DMPC membrane. In addition, we observed cholesterol-induced DA expulsion from both DMPS and DMPC membranes. We believe that this work will provide a more in-depth understanding of DA-membrane interaction at a molecular level.

Curcumin-Induced Membrane Property Changes in DMPC Multilamellar Vesicles and the Effects of Membrane-Destabilizing Molecules on Curcumin-Loaded Multilamellar Vesicles.

Curcumin (CUR) is the major bioactive component of turmeric (Curcuma longa), commonly used as a spice and traditional medicine in India. CUR possesses a wide range of pharmacological benefits, including antioxidant, anticarcinogenic, antimutagenic, anti-inflammatory, anti-Alzheimer, and anti-Parkinson effects. The CUR-membrane interaction is believed to be the reason for such biological activity of CUR. Several research groups have modeled the interaction of CUR with artificial model lipid membranes using various techniques such as nuclear magnetic resonance (NMR), small-angle X-ray scattering (SAXS), and differential scanning calorimetry (DSC). However, the mechanism of its action is still unclear. A fluorescent-probe-based technique could be advantageous to study the CUR-lipid membrane interaction due to its sensitivity toward the local environment and its multiparametric nature. In this work, we have used the intrinsic fluorescence properties of CUR to investigate CUR-induced physical property changes in 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) multilamellar vesicles (MLVs) at various CUR concentrations. By rationalizing the results of steady-state fluorescence intensity, fluorescence anisotropy, temperature-dependent fluorescence intensity, temperature-dependent fluorescence anisotropy, and quenching experiments, we have proposed a model showing concentration-dependent effects of CUR on the DMPC bilayer membrane. We suggest that at low concentrations (≤1 mol %), CUR is homogeneously distributed in the DMPC bilayer membrane in both the solid gel (SG) and liquid crystalline (LC) phases. At high concentrations (>1 mol %), CUR molecules form segregated domains that fluidize both membrane phases. However, the CUR-induced fluidization is less pronounced in the LC phase as some CUR molecules from the domain partition into the bilayer core. Further, the effects of membrane-destabilizing molecules such as bile salts, capsaicin (CAP), and piperine (PIP) on CUR-loaded DMPC multilamellar vesicles were studied. Our work also shows that CUR has a stabilizing effect on the DMPC membrane at high concentrations.

Introducing Tween-curcumin niosomes: preparation, characterization and microenvironment study.

In this work, we report unusual niosomes (non-ionic surfactant based vesicles), prepared using non-ionic surfactant Tween 80 (T80) as well as Tween 20 (T20) and curcumin. Conventional niosomes consist of non-ionic surfactant and cholesterol. We found that, despite being a probiotic, curcumin plays a similar role to cholesterol in the formation and stabilization of niosomes. The prepared Tween-curcumin niosomes were characterised using Dynamic Light Scattering (DLS), zeta potential, Scanning Electron Microscopy (SEM), Atomic Force Microscopy (AFM), and Transmission Electron Microscopy (TEM) techniques. The curcumin-induced micelle to vesicle transition in the Tween surfactants was investigated by DLS, zeta potential, fluorescence anisotropy, and fluorescence lifetime studies. At room temperature (298 K), the prepared niosomes were found to be stable; however, at a higher temperature (333 K), the niosomes degrade gradually and irreversibly to form micelles. The temperature-dependent vesicle to micelle degradation was monitored using fluorescence anisotropy, absorption, DLS and Differential Scanning Calorimetry (DSC) measurements. Further, the Tween-curcumin niosomes show a controlled release of curcumin, which could open up the possibility of multidrug therapy.