Increase in anionic Fe3O4 nanoparticle-induced membrane poration and vesicle deformation due to membrane potential - an experimental study.

The membrane potential plays a significant role in various cellular processes while interacting with membrane active agents. So far, all the investigations of the interaction of nanoparticles (NPs) with lipid vesicles have been performed in the absence of membrane potential. In this study, the anionic magnetite NP-induced poration along with deformation of cell-mimetic giant unilamellar vesicles (GUVs) has been studied in the presence of various membrane potentials. Lipids 1,2-dioleoyl-sn-glycero-3-phospho-(1'-rac-glycerol) (DOPG), 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), and channel forming protein gramicidin A (GrA) are used to synthesize the DOPG/DOPC/GrA-GUVs. The static and dynamic nature of GUVs is investigated using phase contrast fluorescent microscopy. The presence of GrA in the membrane decreases the leakage constant of the encapsulating fluorescent probe (calcein) in the absence of membrane potential. With the increase of negative membrane potential, the leakage shifts from a single exponential to two exponential functions, obtaining two leakage constants. The leakage became faster at the initial stage, and at the final stage, it became slower with the increase in negative membrane potential. Both the fraction of poration and deformation increase with the increase of negative membrane potential. These results suggested that the membrane potential enhances the NP-induced poration along with the deformation of DOPG/DOPC/GrA-GUVs. The increase of the binding constant in the NPs with membrane potential is one of the important factors for increasing membrane permeation and vesicle deformation.

Characterization of phytoconstituents and evaluation of antimicrobial activity of silver-extract nanoparticles synthesized from Momordica charantia fruit extract.

BACKGROUND: Our present study was conducted to characterize the phytoconstituents present in the aqueous extract of Momordica charantia and evaluate the antimicrobial efficacy of silver-extract nanoparticles (Ag-Extract-NPs). METHODS: Silver nanoparticles (AgNPs) were prepared by reducing AgNO3; and NaBH4 served as reducing agent. After screening of phytochemicals; AgNPs and aqueous extract were mixed thoroughly and then coated by polyaniline. These NPs were characterized by using Visual inspection, UV spectroscopy, FTIR, SEM and TEM techniques. Antimicrobial activities were assessed against Staphylococcus aureus, Salmonella typhi, Escherichia coli and Pseudomonas aeruginosa. RESULTS: Aqueous extract of M. charantia fruits contain alkaloid, phenol, saponin etc. UV-Vis spectrum showed strong absorption peak around 408 nm. The presence of -CH, -NH, -COOH etc. stretching in FTIR spectrum of Ag-Extract-NPs endorsed that AgNPs were successfully capped by bio-compounds. SEM and TEM result revealed that synthesized NPs had particle size 78.5-220 nm. Ag-Extract-NPs showed 34.6 ± 0.8 mm zone of inhibition against E. coli compared to 25.6 ± 0.5 mm for ciprofloxacin. Maximum zone of inhibition for Ag-Extract-NPs were 24.8 ± 0.7 mm, 26.4 ± 0.4 mm, 7.4 ± 0.4 mm for S. aureus, P. aeruginosa and S. typhi. We found that Ag-Extract-NPs have much better antibacterial efficacy than AgNPs and M. charantia extract has individually. It is also noticed that gram negative bacteria (except S. typhi) are more susceptible to Ag-Extract-NPs than gram positive bacteria. CONCLUSION: Ag-Extract-NPs showed strong antibacterial activity. In order to make a reliable stand for mankind, further study is needed to consider determining the actual biochemical pathway by which AgNPs-extracts exert their antimicrobial effect.

Anthelmintic activity of silver-extract nanoparticles synthesized from the combination of silver nanoparticles and M. charantia fruit extract.

BACKGROUND: Present study has been conducted to know the anthelmintic activity of polyaniline coated silver nanoparticles (AgNPs) synthesized from Momordica charantia fruit extract. METHODS: By reduction of AgNO3 in presence of NaBH4, silver nanoparticles were prepared. After mixing silver nanoparticles and extracts, coating was given on nanoparticles using polyaniline. Prepared nanoparticles were characterized by Visual, UV, FTIR spectroscopy, SEM techniques, and TEM analysis. RESULTS: The FTIR results implied that AgNPs were successfully synthesized and capped with bio-compounds present in the extract. The result showed that death times of worm were 35.12 ± 0.5 and 59.3 ± 0.3 minutes for M. charantia extract and Ag-nanoparticles individually. But when these two combined together, paralysis and death time fall drastically which were only 6.16 ± 0.6 and 9.1 ± 0.4 minutes respectively. Albendazole tablet was used as standard, which made worms death in 3.66 ± 0.1 minutes. CONCLUSION: Ag-Extract NPs showed strong anthelmintic activity against worm. This study has paved the way for further research to design new anthelmintic drug from the combination of M. charantia and AgNPs.

Effects of membrane potentials on the electroporation of giant unilamellar vesicles.

Living organisms maintain a resting membrane potential, which plays an important role in various biophysical and biological processes. In the context of medical applications, irreversible electroporation (IRE) is a non-thermal and minimally invasive technique that utilizes precisely controlled electric field pulses of micro- to millisecond durations to effectively ablate cancer and tumor cells. Previous studies on IRE-induced rupture of cell-mimetic giant unilamellar vesicles (GUVs) have primarily been conducted in the absence of membrane potentials. In this study, we investigated the electroporation of GUVs, including parameters such as the rate constant of rupture and the probability of rupture, in the presence of various negative membrane potentials. The membranes of GUVs were prepared using lipids and channel forming proteins. As the membrane potential increased from 0 to -90 mV, the rate constant of rupture showed a significant increase from (7.5 ± 1.6)×10-3 to (35.6 ± 5.5)×10-3 s-1. The corresponding probability of rupture also exhibited a notable increase from 0.40 ± 0.05 to 0.68 ± 0.05. To estimate the pore edge tension, the electric tension-dependent logarithm of the rate constant was fitted with the Arrhenius equation for different membrane potentials. The presence of membrane potential did not lead to any significant changes in the pore edge tension. The increase in electroporation is reasonably explained by the decrease in the prepore free energy barrier. The choice of buffer used in GUVs can significantly influence the kinetics of electroporation. This study provides valuable insights that can contribute to the application of electroporation techniques in the biomedical field.

Nigella sativa Oil Improves Motor Skill Learning of Albino Mice: In Vivo and In Silico Investigations.

Experimental evidences demonstrated that Nigella sativa oil (NSO) can restore neuronal integrities and processes by increasing the neuronal density, decreasing apoptosis, preventing inflammatory processes, and improving the neurogenic cells in the hippocampus. This refurbishment enhances the learning process and memory. The antioxidant defense mechanism of NSO slows down the process of neurodegeneration and motor deficit. The present study aimed to investigate the effects of NSO on motor skill learning using the single pellet reaching task method on Swiss albino mice, followed by in silico studies. Mice (total of 16) were randomly divided into the control group and treatment group (n = 8). The treatment group received 1 ml/kg b.w. NSO orally once daily for 7 days, and a control group received 1 ml/kg normal saline instead of NSO in a similar manner. The average success rate due to ingestion of NSO in the treatment group mice increased significantly (P < 0.05) compared to controlled mice. Molecular docking analysis revealed that thymoquinone, carvacrol, thymohydroquinone, p-cymene, and t-anethole have binding affinities for the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPA-R) that ranges from (-5.1 to -6.2) kcal/mol, which is comparable to the reference ligand glutamic acid binding affinity with AMPA-R (-6.6 kcal/mol). Thymoquinone and carvacrol formed hydrogen bonds with AMPA receptor at TYR61, SER142, and SER143 residues, comparable to the binding affinity of glutamic acid. ADMET analysis reported that all the compounds have higher bioavailability (>90%) and can cross the BBB easily (logBB> 0.3). Based on our experimental data and in silico report, we concluded that the enhanced motor skill learning effects of NSO are due to presence of potent antioxidants-thymoquinone and carvacrol-which might serve as AMPA receptor agonists. These phytoconstituents may play role in synaptic strengthening and promote experience-dependent motor skill learning.

Anthropometry in predicting Semitendinosus and Gracilis graft diameter for arthroscopic ACL reconstruction among the Bengali population.

Semitendinosus and Gracilis autografts are commonly used for anterior cruciate ligament (ACL) reconstruction. However, its main drawback is individual variation in the tendon diameter. This study aimed to evaluate the usefulness of the anthropometric measurements for the prediction of Semitendinosus and Gracilis combined (quadrupled) strands graft diameter in arthroscopic ACL reconstruction among the Bengali population. Sixty consecutive patients who underwent ACL reconstruction between July 2019 to June 2020 were observed in this cross-sectional study. In all cases, the doubled (2 strands) Gracilis and Semitendinosus tendons were combined to get the final quadrupled (combined 4 strands) graft for use. Anthropometries such as body mass index (BMI), body weight, and height were recorded preoperatively and quadrupled combined tendon diameter was measured at the operating theater. The relationship between these parameters was statistically determined using the Pearson correlation coefficient, and scatter diagrams were plotted. Among the study subjects, most (54) were male, and the mean age of all subjects was 24 ±â€…6.92 years. The average graft diameter was 7.20 ±â€…0.76 mm. Correlations between the mean graft diameter with BMI (r = 0.018, and P = .891), body height (r = 0.011 and P = .933), and weight (r = 0.028 and P = .832) were not significant. Scatter diagrams also showed that the variables were not correlated. Anthropometries like BMI, body weight, or body height cannot be used in predicting Semitendinosus and Gracilis tendon graft diameter for arthroscopic ACL reconstruction among the Bengali population.

Assessment of Polyunsaturated Fatty Acids on COVID-19-Associated Risk Reduction.

Pooled evidence conveys the association between polyunsaturated fatty acids and infectious disease. SARS-CoV-2, an enveloped mRNA virus, was also reported to interact with polyunsaturated fatty acids. The present review explores the possible mode of action, immunology, and consequences of these polyunsaturated fatty acids during the viral infection. Polyunsaturated fatty acids control protein complex formation in lipid rafts associated with the function of two SARS-CoV-2 entry gateways: angiotensin-converting enzyme-2 and cellular protease transmembrane protease serine-2. Therefore, the viral entry can be mitigated by modulating polyunsaturated fatty acids contents in the body. α-Linolenic acid is the precursor of two clinically important eicosanoids eicosapentaenoic acid and docosahexaenoic acid, the members of ω-3 fats. Resolvins, protectins, and maresins derived from docosahexaenoic acid suppress inflammation and augment phagocytosis that lessens microbial loads. Prostaglandins of 3 series, leukotrienes of 5 series, and thromboxane A3 from eicosapentaenoic acid exhibit anti-inflammatory, vasodilatory, and platelet anti-aggregatory effects that may also contribute to the control of pre-existing pulmonary and cardiac diseases. In contrast, ω-6 linoleic acid-derived arachidonic acid increases the prostaglandin G2, lipoxins A4 and B4, and thromboxane A2. These cytokines are pro-inflammatory and enhance the immune response but aggravate the COVID-19 severity. Therefore, the rational intake of ω-3-enriched foods or supplements might lessen the complications in COVID-19 and might be a preventive measure.

Propagation of age-related diseases due to the changes of lipid peroxide and antioxidant levels in elderly people: A narrative review.

Background and Aims: Lipid peroxidation end products are the major culprit for inducing chronic diseases in elderly people. Along with the elevated level of lipid peroxide biomarkers, there is a significant disruption of antioxidants balance, which combinedly propagate the diseases of elderly people. The aim of the present review is to bridge the connection of changes in lipid peroxides biomarkers and antioxidants level with age-associated diseases in elderly people. Methods: This narrative review was performed following a comprehensive search for suitable articles in multiple online databases, including PubMed, Google Scholar, EMBASE, Web of Science, Cochrane Library, and ScienceDirect using selected search terms. The most appropriate literature was included based on the selection criteria. Results: From the review, it is found that many age-related diseases propagated with an increased level of the end products of lipid peroxide and reduced levels of antioxidants in elderly people. When the end products of lipid peroxidation increase in the body, it creates oxidative stress, which ultimately leads to many complicated diseases, including cancers, cardiovascular and neurogenic diseases, and many other chronic inflammatory diseases. The oxidative stress induced by peroxidation can be assessed by different lipid peroxide end products such as malondialdehyde, oxidized low-density lipoprotein, isoprostanes, neuroprostanes, lipoperoxides, oxysterols (7-ketocholesterol, 7ß-hydroxycholesterol), and many more. Conclusions: This study definitively answers the correlation between the changes in lipid peroxides and antioxidants level and age-related diseases. Our narrative article recommends future investigations for elucidating the mechanisms rigorously to establish a compact correlation.

Effect of membrane potential on pore formation by the antimicrobial peptide magainin 2 in lipid bilayers.

The effect of membrane potential on plasma membrane damage generated by antimicrobial peptides (AMPs) is an important, yet poorly characterized, process. Here, we studied the effect of membrane potential (φm) on pore formation by magainin 2 (Mag) in single giant unilamellar vesicles (GUVs) composed of dioleoylphosphatidylglycerol (DOPG)/dioleoylphosphatidylcholine (DOPC) membranes. Various membrane potentials in GUVs containing gramicidin A were generated as a result of K+ concentration gradients. First, we examined Mag-generated membrane permeation of the water-soluble fluorescent probe calcein in single DOPG/DOPC-GUVs in the presence of membrane potential. The results indicate that the rate constant (kp) of Mag-induced pore formation increased with increasing negative membrane potentials. Analysis of the rim intensity of single GUVs interacting with low concentrations of a fluorescent probe, carboxyfluorescein-labeled Mag (CF-Mag), using confocal laser scanning microscopy (CLSM) shows that the concentration of CF-Mag in the membrane greatly increased with negative membrane potentials. This indicates that the binding constant of CF-Mag to the membrane increased with more negative membrane potentials. To elucidate the location of Mag in a GUV with φm during Mag-induced pore formation, we examined the interaction of Mag and a low concentration of a CF-Mag mixture with single GUVs containing the water-soluble fluorescent probe AF647 using CLSM. The data indicate that CF-Mag locates in the external leaflet of single GUVs until just before pore formation. Based on these data, we conclude that the increase in the surface concentration of Mag is one of the primary causes of the increase in kp with negative membrane potential.