Destruction Of Membrane Research Articles

Synuclein Family Members Prevent Membrane Damage by Counteracting α-Synuclein Aggregation.

The 140 amino acid protein α-synuclein (αS) is an intrinsically disordered protein (IDP) with various roles and locations in healthy neurons that plays a key role in Parkinson’s disease (PD). Contact with biomembranes can lead to α-helical conformations, but can also act as s seeding event for aggregation and a predominant β-sheet conformation. In PD patients, αS is found to aggregate in various fibrillary structures, and the shift in aggregation and localization is associated with disease progression. Besides full-length αS, several related polypeptides are present in neurons. The role of many αS-related proteins in the aggregation of αS itself is not fully understood Two of these potential aggregation modifiers are the αS splicing variant αS Δexon3 (Δ3) and the paralog β-synuclein (βS). Here, polarized ATR-FTIR spectroscopy was used to study the membrane interaction of these proteins individually and in various combinations. The method allowed a continuous monitoring of both the lipid structure of biomimetic membranes and the aggregation state of αS and related proteins. The use of polarized light also revealed the orientation of secondary structure elements. While αS led to a destruction of the lipid membrane upon membrane-catalyzed aggregation, βS and Δ3 aggregated significantly less, and they did not harm the membrane. Moreover, the latter proteins reduced the membrane damage triggered by αS. There were no major differences in the membrane interaction for the different synuclein variants. In combination, these observations suggest that the formation of particular protein aggregates is the major driving force for αS-driven membrane damage. The misbalance of αS, βS, and Δ3 might therefore play a crucial role in neurodegenerative disease.

0D/2D CQDs/Bi7O9I3 composite with high photocatalytic disinfection performance under visible light

The development of sustainable and efficient photocatalysts for water disinfection has always been the challenge. Herein, 0D CQDs are grown in situ onto 2D Bi7O9I3 microsheets successfully for the first time, constructing a series of CQDs/Bi7O9I3 composite catalysts for photocatalytic disinfection. Compared with pure Bi7O9I3, the optimal 2-CB exhibits the highest photocatalytic antibacterial (99.99%) and degradation activity, which is attributed to the synergistic effect of CQDs and Bi7O9I3. CQDs can be used as photosensitizers to enhance light absorption and electron acceptors to promote the separation of photogenerated charge carriers. The leakage of K+ ions and the structural destruction of the cell membrane cause bacteria death. Free radical trapping experiment proves that h+ plays a critical role on bacteria inactivation. The possible photocatalytic disinfection mechanism is also proposed. This work sheds light on designing highly-efficient photocatalysts toward water disinfection.

ОКТ-морфологические параллели при меланомах хориоидеи

It is known that OCT-detected retinal changes are comparable with histology resalts. Choroidal structure on EDI-OCT also comparable with histology. Purpose. To compare OCT-changes with pathomorphology in same microscopic sections. Material and methods. The analysis of OCT tomograms of 5 patients with choroidal melanomas (CM), who subsequently underwent primary enucleation. The patients age was 55,2±10,57 years. The maximum CM elevation is 4,85±1,76 mm, the maximum diameter is 13,09±4,14 mm. Results and discussion. The correlation of tomographic and histological picture was obtained in the following signs: signs of destruction of Bruch's membrane, the presence of hyperreflective changes at the RPE level, photoreceptors changes, the presence of neuroepithelial detachment, the presence of intraretinal cavities. Partial correlation - for signs of the presence of subretinal transudate and infiltration of the outer layers of the retina. No correlation was obtained for the signs of infiltration of the inner retina layers and the inner limitans membrane breakthrough with CM dissemination on a retinal surface. Conclusions. Comparison of OCT signs of MC with pathomorphological studies in 5 enucleated eyes made it possible to expand the interpretation of signs of CM spreading on OCT beyond the Bruch's membrane with the tumor growth zones formation in the retina. Key words: choroidal melanoma, optical coherence tomography of the retina, histological examination.

Combination of cisplatin treatment and photodynamic therapy attenuates cisplatin-induced cell toxicity in A2780 and A2780-CP cervical cancer cell lines.

Cervical cancer is recognized as a serious worldwide health problem. Despite various achievements for cervical cancer treatment, there are still shortcomings that lead to severe side effects. Combination therapy is fast becoming a key and promising treatment strategy, diminishing chemotherapy-mediated side effects. The objective of this study was to determine the effect of combined cisplatin treatment and photodynamic therapy (PDT) on the cervical cancer recovery. In this study, A2780 and A2780-CP cell lines were cultured in the Dulbecco's modified eagle medium (DMEM) enriched with 10% FBS and 1% antibiotic. Both cell lines were treated with cisplatin, photodynamic light (laser with methylene blue as a photosensitizer agent), and the combination of cisplatin treatment and PDT. Half maximum inhibitory concentration (IC50) was calculated for each treatment by the use of tetrazolium salt assay. Both cell lines were examined for cell membrane lipid peroxidation rate. Our findings showed that combination of cisplatin treatment and photodynamic therapy leads to two-fold decreased cisplatin IC50. Results showed that cisplatin and photodynamic light combination could effectively reduce A2780 and A2780-CP cell viability (p-value < 0.0001). Moreover, combined cisplatin and photodynamic therapy results revealed significantly increased cancer cell membrane destruction through increased lipid peroxidation, resulting in surged MDA content. Our conclusion is that combination of cisplatin and photodynamic therapy can be used as an effective and convenient treatment strategy without considerable side effects.

THE CORRELATION BETWEEN TERPENOID OF SARANG SEMUT (Myrmecodia pendans) WITH mRNA FRUCTOSYLTRANFERASE EXPRESSION OF Streptococcus mutans BIOFILM ATCC 25175

Background: Terpenoid isolate sarang semut (Myrmecodia pendans) is a natural material that has antibacterial power through the destruction of the cell membrane of Streptoccus mutans (S. mutans). Fructosiltransferase (ftf) is one of the extrapolisaccharides produced by S. mutans. The formation of Ftf is governed by the ftf gene. The aim of research was to know the correlation between terpenoid of Sarang semut administration with ftf mRNA expression of S. mutans biofilm ATCC 25175. Method: The study used mixed methods, namely descriptive explorative method to look at the isolation of ftf gene and ftf mRNA expression. This study began with making 1 day biofilm , then given terpenoid isolates of sarang semut and chlorhexidine. Next, isolation of ftf genes and ftf mRNA expression was carried out, then the differences in S. mutans ATCC 25175 mRNA ftf expression in sarang semut and chlorhexidine were given for 1 and 30 minutes using Real-Time PCR. Continued by looking at the relationship of the duration of administration of sarang semut terpenoids to the expression of S. mutans ATCC 25175 mRNA ftf biofilm. Statistical analysis used the t test with p-value &lt;0.05 and Pearson. Results: The results showed that ftf gene with 130 bp length and ftf mRNA expression could be isolated from S. mutans biofilm ATCC 25175 which were given terpenoid isolates from sarang semut. The expression of sarang semut mRNA ftf and chlorhexidine did not have a significant difference for 1 minute (p = 0.0761), whereas in 30 minutes the ant nest had a higher mRNA expression (p = 0.0186). There is a relationship between the duration of administration of terpenoid isolates of sarang semut with S. mutans ATCC 25175 mRNA ftf expression (r2 = 0.614), with a medium correlation coefficient. Conclusion: The conclusion of the study were that sarang semut terpenoid had the same effect as chlorhexidine for 1 minute on S. mutans biofilms, whereas at 30 minutes it was different. There is a relationship between terpenoids of sarang semut isolates and S. mutans biofilm ATCC 25175 mRNA expression.

Psidium Guajava L. Extract Against Minimum Inhibitory Concentration of Staphylococcus Aureus

The aim of this research was to evaluate the effects on the growth of Staphylococcus Aureus bacteria in vitro of antibacterial activity of guayava leaf extract (Psidium guajava L.) and guavava leaf extract impact on the growth of staphylococcus Aureus bacteria at different laboratory concentrations. In this experiment, S. Aureus bacteria are being treated to guava leaf extract to identify the lowest inhibitory power for well techniques, and the results have been recorded. The Guava leaf extract (Psidium Guajava L) against Staphylococcus aureus was found to have an inhibitory zone diameter of mm in the absence of tetracycline, and DMSO as a negative control. Findings were observed using the disk diffusion technique or paper disc with concentrations of 1 percent, 3 percent, 5 percent, and 7 percent. Saponins, saponins, alkaloids, and flavonoids found in guava leaves are responsible for their antibacterial effects. Saponins have the potential to disturb the integrity of bacterial cell membranes. This results in bacterial cell membrane destruction, releasing essential components from the cell

Solvent induced distortion in a square planar copper(II) complex containing an azo-functionalized Schiff base: Synthesis, crystal structure, in-vitro fungicidal and anti-proliferative, and catecholase activity

This research work reports the synthesis, single crystal X-ray structure, catechol oxidation, fungicidal and antiproliferative activity of a newly synthesized copper(II) complex, [Cu(L)2]H2O . CH3OH (1) containing an azo-functionalized Schiff base, HL = 2-methoxy-6-((Z)-((4-((E)-phenyldiazenyl)phenyl)imino)methyl)phenol. The crystal structure analysis reveals that the Cu(II) centre exists in a highly distorted square planar geometry. The crystallize water and methanol form a strong intermolecular association through H-bonding. More importantly, the H atoms of the lattice water interact with the O atoms of ligand units leading to 5- and 6-membered cycles through the H-bonding network and distort the square planar geometry. The copper(II) complex has emerged as a bioinspired catalyst in the oxidative transformation of 3,5-di-tert-butylcatechol (DTBC) to o-benzoquinone in methanol with a high turnover number, 4.75 × 102 h–1. Electrochemical analysis of the copper(II) complex in presence of DTBC recommends the generation of catechol/o-benzosemiquinone redox couple in the course of oxidation. The EPR spectral analysis of 1 in presence of DTBC was found silent and suggested the antiferromagnetic interaction between copper centre and benzosemiquinone species. The copper(II) complex turns out to be a potential fungicidal agent against clinical candida albicans and scanning electron microscope studies confirm the destruction of the fungal cell membrane with the deposition of copper. The IC50 value of the copper complex was determined as 15 µg/mL which suggests the excellent antiproliferative potency of the synthetic compound against the breast cancer cell lines, MCF-7.

RISK FACTORS FOR MALIGNANCY OF PAPILLOMAS IN THE OROPHARYNGEAL MUCOUS MEMBRANE ASSOCIATED WITH HUMAN PAPILLOMAVIRUS (HPV)

Analysis of the HPV positive papilloma structures at different levels of pathological process development was carried out. Classical staining of preparations with hematoxylin and eosin was used for immunohistochemical determination of Ki67-positive cells and phenotyping of CD positive cells. We found that the process of papilloma formation begins with a local increase in the proliferative activity of keratinocytes which contributes to the formation of a local epithelial convex above the surface of the oropharyngeal mucosa (OPM) in the form of papilloma. The connective tissue of the OPM adjacent to the epithelium grows at the second stage. At the same time here is a decrease in immunocytes/macrophages number of the oral epithelium not only in the growth zone of the papilloma but in the adjacent neoplasm tissue. The third stage is characterized by the destruction of the basal membrane of the OPM. Apoptotic cells in the cambial layer and forming leukocytes infiltrate the OPM lamina propria. Virus-infected keratinocytes are phagocytized by macrophages or exfoliated from the surface of the epithelial layer. The emerging in the middle layers defect of tissue of the epithelial layer and the absence of Langerhans cells indicate a relationship between the migration of antigen-presenting cells expressing CD68 with impaired differentiation and specialization of keratinocytes. The conclusion is based on the analogy of "leukemic failure" in leukemia and on the absence of differentiating epithelial cells between the cambium and the specialized surface layer in the long-existing papilloma. The disappearance from the epithelium of CD68-positive cells specific to the epithelial layer is a prognostic sign of malignization in the mucous membrane of the oropharynx.

Application of Nanotechnologies in Studying Yeast Structure in Candida

This review considers the methods of probe, electron, and confocal microscopy for studying the structure of the yeast Candida. The latest advances in the study of antimicrobial effects by high-resolution microscopy are presented. The advantages and disadvantages of each method are presented, as well as the limits of their application. Processes such as cell wall lysis and destruction of the cytoplasmic membrane caused by antifungal drugs are described, as well as their effect on the nanostructural or mechanical properties of Candida. Particular attention is paid to sample preparation of Candida and scanning protocols.

Plasma induced efficient removal of antibiotic-resistant Escherichia coli and antibiotic resistance genes, and inhibition of gene transfer by conjugation

Antibiotic-resistant bacteria (ARB) and their resistance genes (ARGs) are emerging environmental pollutants that pose great threats to human health. In this study, a novel strategy using plasma was developed to simultaneously remove antibiotic-resistant Escherichia coli (AR bio-56954 E. coli) and its ARGs, aiming to inhibit gene transfer by conjugation. Approximately 6.6 log AR bio-56954 E. coli was inactivated within 10 min plasma treatment, and the antibiotic resistance to tested antibiotics (tetracycline, gentamicin, and amoxicillin) significantly decreased. Reactive oxygen and nitrogen species (RONS) including •OH, 1O2, O2•−, NO2−, and NO3− contributed to ARB and ARGs elimination; their attacks led to destruction of cell membrane, accumulation of excessive intracellular reactive oxygen substances, deterioration of conformational structures of proteins, and destroy of nucleotide bases of DNA. As a result, the ARGs (tet(C), tet(W), blaTEM-1, aac(3)-II), and integron gene intI1), and conjugative transfer frequency of ARGs significantly decreased after plasma treatment. The results demonstrated that plasma has great prospective application in removing ARB and ARGs in water, inhibiting gene transfer by conjugation.

Antifungal mechanisms of lavender essential oil in the inhibition of rot disease caused by Monilinia fructicola in postharvest flat peaches

Lavender essential oil (LEO), a natural antimicrobial agent, is generally recognized as safe and effective in the inhibition of phytopathogenic fungi. Direct contact and fumigation (in vivo and in vitro) were used to study the fungistatic effect of LEO on Monilinia fructicola. Additionally, the effect on the ultrastructure of cells and the degree of destruction of the cell membrane of M. fructicola were revealed. In addition, the effects of LEO on the expression levels of apoptosis-related genes in M. fructicola cells were detected, and GC-MS was used to analyze the main components of LEO. LEO had a good inhibitory efficacy against M. fructicola in flat peaches, with almost complete growth inhibition at 800 μL/L. These effects were associated with the leakage of cytoplasmic contents, hyphal distortion, and spore disruption. Moreover, the expression of apoptosis RTG1 and RLM1 genes increased with LEO treatment. These results demonstrate that LEO can inhibit M. fructicola by inducing cytoplasmic membrane damage and cell apoptosis in fungi, and that the major ingredients of LEO are monoterpenes and sesquiterpenes, which are presumed to contribute to the inhibitory effects.

Bifunctional cupric oxide nanoparticle-catalyzed self-cascade oxidation reactions of ascorbic acid for bacterial killing and wound disinfection

The emergence of drug-resistant bacterial strains has challenged the use of traditional antibiotic therapies. Therefore, there is an urgent need to develop novel antibacterial materials or methods to effectively eradicate bacteria. Herein, we demonstrated a novel antibacterial system consisting of cupric oxide nanoparticles combined with ascorbic acid (CuO NPs/AA), which could act as a potent nanoantibiotic targeting both Escherichia coli (gram-negative) and Staphylococcus aureus (gram-positive) in vivo and in vitro, without noticeable cytotoxicity to mammalian tissue. The CuO NP/AA antibacterial system killed these microbes through a combined mechanism involving biofilm inhibition, cell membrane destruction, DNA damage, and enzyme inactivation. The antibacterial properties of CuO NPs/AA were mainly attributed to the generation of reactive oxygen species (e.g., ·OH) produced through the intrinsic ascorbate oxidase- and peroxidase-like activities of CuO NPs, highlighting their use as antibacterial nanozymes to treat bacterial infections.

Potassium permanganate as a promising pre-oxidant to treat low-viability cyanobacteria and associated removal of cyanotoxins and extracellular organic matters

Cell-viability of cyanobacteria declines from development to decay stage during a successive bloom. Potassium permanganate (KMnO4) has demonstrated to be a superior pre-oxidant to treat high-viability cyanobacteria compared to other common oxidants (e.g., chlorine), but whether it is feasible to treat low-viability cyanobacteria is unknown. Here, effects of KMnO4 on membrane integrity, cyanotoxin fate and extracellular organic matters (EOMs) removal of high- and low-viability cyanobacteria were compared. Results showed that cell-viability of cyanobacteria could affect oxidant decay (kdecay), membrane damage (kloss), and cyanotoxins release (ki) and degradation (ke) during KMnO4 oxidation, similar to chlorination. However, unlike chlorination, initial low dosages of KMnO4 (0.5 and 1 mg L−1) minimized membrane damage for low-viability cyanobacteria (< 27%), and continuously decrease extracellular cyanotoxins, extracellular organic matters (EOMs), and aromatic compounds to some degrees (P<0.05). High dosages of KMnO4 (> 2 mg L−1) caused severe membrane destruction (> 89%) for low-viability cyanobacteria, leading to a fast increase of extracellular cyanotoxins within 1 h. However, total/extracellular cyanotoxins were oxidized to below the safety guideline of 1 μg L−1 after being dosed with sufficient oxidant exposure. EOMs and aromatic compounds were also reduced by 5–18% (P<0.05). Additionally, KMnO4-assisted coagulation significantly improved the removal of low-viability cyanobacteria (2–5 fold). Consequently, KMnO4 could be a promising pre-oxidant to treat low-viability cyanobacteria at decay stage of a successive bloom.

Nano-cell and nano-pollutant interactions constitute key elements in nanoparticle-pollutant combined cytotoxicity

As the wide application of carbon nanoparticles (CNPs) and zinc oxide nanoparticles (ZnONPs), as well as ubiquitous chromium (Cr(VI)) pollution in environment, the chance of human exposure to CNPs/ZnONPs and their Cr(VI) adducts is enhanced. We therefore investigated the impacts of nano-cell and nano-Cr(VI) interactions on nanoparticle-Cr(VI) combined cytotoxicity in human lung epithelial (A549) cells. Our results showed that nano-cell and nano-pollutant interactions were the key elements in NP-pollutant combined cytotoxicity, as determined by cell death, oxidative stress and mitochondrial dysfunction. A strong adsorption of Cr(VI) on CNPs and reduction of Cr(VI) to Cr(III) were confirmed, resulting in the reduced cytotoxicity of CNP-Cr(VI) adducts. In contrast, ZnONPs caused the destruction of cell membranes so that more ZnONP-Cr(VI) adducts could enter the cells. Meantime, more Cr contents could be released from ZnONP-Cr(VI) adducts once entering cells and locating in lysosomes than that from CNP-Cr(VI) adducts. These two reasons together caused the enhanced cytotoxicity of ZnONP-Cr(VI) adducts. These findings indicate that the in-depth investigations on the interaction mechanisms are crucial to comprehensively understand the combined cytotoxicity of different NPs and pollutants.

Peculiarities of cytolytic syndrome development with associated injury of the abdominal organs and massive blood loss in the experiment

The function of the organs responsible for detoxification processes, in particular the liver, deserves a special role in the conditions of combined trauma. It is proved that ischemia-reperfusion of the limb caused by the imposition of a tourniquet, is the cause of significant toxemia. Under such conditions, it becomes clear that the detoxification function may be impaired, especially against the background of blunt combined trauma to the abdominal organs complicated by massive bleeding. Changes in the detoxification function of the liver are indicated by markers of the cytolytic syndrome. However, there is no clear understanding of how ischemia - limb reperfusion affects the development of cytolytic syndrome.Objective of research: to study the effect of massive blood loss associated with ischemia-reperfusion of the limb on the cytolytic syndrome indicators in case of injury of the abdominal organs. Materials and methods. 100 mature albino male Wistar rats with the body weight of 190-220 grams kept on standard vivarium forage were used in the experiment. The animals were divided into the control and 3 research groups (containing 10 animals each). Arresting bleeding tourniquet was applied proximally on the lower limbs of rats from the first research group for 120 minutes under thiopental-sodium anesthesia (40 mg/kg-1), which caused development of ischemic-reperfusion. Closed abdominal injury was simulated by means of delivering two dosed blows in the region of the abdominal cavity in the second research group; massive blood loss was simulated by means of cutting the femoral vessels and bloodletting from 25 to 30 % of the circulating blood volume in the group. Injuries from the first two groups were combined in the third group. The control group of animals received anesthesia without formation of any injuries. With the aim to determine alterations of cytolytic syndrome the activity of enzymes – markers of cytolytic syndrome ALT and AST were determined by means of a unified method. The animals of the research groups were removed from the experiment under thiopental-sodium anesthesia by means of the total bloodletting from the heart.Results. Analysis of the results of the study found that cytolytic syndrome develops irrespective of the kind of injuries simulated. Thus, even during a day of post-traumatic period ALT and AST activity increases which is clearly registered in all the three research groups. Further destruction of cellular membranes increases till the 3rd day, which is manifested by a considerable increase of ALT and AST activity in the blood serum. This process continues till the 7th day. A tendency to ALT and AST decrease is observed only in the 1st group on the 7th day. Comparison of the 2nd and 3rd research groups within the time interval enables to understand that application of tourniquets on the limbs of animals with closed abdominal injury and massive bleeding deteriorates cytolytic processes.Conclusions: Simulated injuries in the research groups were associated with the occurrence of cytolytic processes possessing a tendency to develop in the period of early signs of traumatic disease. Ischemic-reperfusion syndrome of the limbs accelerates considerably the development of systemic changes with abdominal injuries and hypovolemic shock, which was manifested by a considerable increase of ALT and AST parameters in the group with abdominal trauma and massive blood loss and becoming higher than that of the control in end of the experiment.

Clinico-hematological profile of hemolytic anaemia at the SAMS medical college hospital

Background: Hemolytic anaemia is caused due to the higher rate of destruction of red cells (membrane) than the rate of their generation. It can be inherited from or acquired. Membrane destruction is majorly caused due to the defects of membrane and enzymes. HA can be diagnosed with laboratory test like complete blood count test, urine test etc. Aims and Objectives: To study the clinical and pathological profile of hemolytic anaemia among the patients at Sri Aurobindo Institute of Medical Sciences (SAMS) medical college hospital. Materials and Methods: This study included 150 patients diagnosed with HA for 12 months from Feb 2019 to March 2020. Clinico-Hematological profile of each patients was recorded. Results: Current study observed that the 39.33% had beta thalassemia trait, sickle cell anaemia in 18.7%, beta thalassemia in 167.7%, malaria in 12%, sickle beta thalassemia 4.7%, and sickle cell trait. HA was more prevalent among male subjects (59%). Mean haemoglobin was least in thalassemia major (5.2gm/dl) and highest in sickle cell trait (9.2gm/dl). Mean total serum bilirubin was highest in beta thalassemia major patients and highest in beta thalassemia major (1821.4ng/dl). jaundice (57%), splenomegaly (47%) and hepatomegaly (34%) were common clinical manifestations. Conclusion: HA is more prevalent among younger male population; beta thalassemia trait and sickle cell anaemia are the most common HA. Other than the hereditary causes malaria is the major cause HA. Keywords: Hemolytic anaemia, Hemoglobin, Intracorpuscular and extracorpuscular.

Chitosan resistance by the deletion of the putative high affinity glucose transporter in the yeast Ustilago maydis

Chitosan is a polycationic amino-sugar polymer soluble in acidic pH. As a potential antifungal, it has been tested against several fungi. Its main mode of action is the permeabilization of cell membrane by the interaction with specific membrane sites. Ustilago maydis, an attractive fungal model used in biochemical and biotechnology research, is highly sensitive to chitosan, with extensive membrane destruction that results in cell death. Using the Golden Gate system, several mutant strains with deletions in monosaccharide transporters were obtained and tested against chitosan in order to know the implications of these membrane proteins in the sensitivity of the fungus against chitosan. Δum11514/03895 strain, a mutant with a deletion in a hypothetical high affinity glucose transporter, showed resistance to chitosan. Morphological characterization of the mutant displayed an apparent increase in mitochondrial content, but oxygen consumption as well as growth rate were not affected by the gene deletion. Alteration in cell wall surface was observed in the mutant strain. In contrast to wild type, the Δum11514/03895 strain showed integrity of cell wall and cell membrane in the presence of chitosan. The resistance against chitosan is likely associated to the modification of cell wall architecture and is not related to energy-depend process.

A mechanistic study on the inhibition of bacterial growth and inflammation by Nerium oleander extract with comprehensive in vivo safety profile

BackgroundNerium oleander (L.) is well known traditionally used medicinal plant with several pharmacological activities. However, the anti-bacterial, anti-inflammatory activity and in vivo toxicity potential of floral parts of this plant are not reported. Therefore the present study was designed to investigate these activities of Nerium oleander ethanolic flower extract (NOEE) in different animal models.MethodsAntimicrobial activity of plant extract was compared with five different antibiotics using the disk diffusion method. The time-killing kinetic assay and bacterial killing mechanism of NOEE were also performed. Anti-inflammatory activity was assessed using granuloma induced by cotton-pellet, rat paw edema induced by carrageenan and levels of different inflammatory biomarkers on healthy Wistar rats. The protein and mRNA expressions of nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were also measured. Acute (14 days) and sub-acute (28 days) oral toxicity studies were also performed on healthy Sprague Dawley rats.ResultsNOEE produced highly significant (P < 0.005) and significant (P < 0.05) zones of inhibition at 30 mg/mL and 20 mg/mL respectively against most of the tested bacterial strains. NOEE produced a more drop in viable counts of Gram-negative isolates within 20 min. After 12 h exposure with NOEE, the SEM images of MRSA showed the destruction of cell membrane. NOEE showed highly significant (P < 0.005) anti-inflammatory activity in cotton-pellet and carrageenan inflammatory models. In addition, treatment with NOEE also decreased the production of NO, PGE2, TNF-α and IL-1β in the rat paw after treated with carrageenan. Similarly, NOEE also suppressed the inducible nitric oxide synthase (iNOS), TNF-α, IL-1β, and cyclooxygenase-2 (COX-2) mRNA expressions. It is also showed highly significant reduction in total leukocyte count (73.09%) and C-reactive protein levels (54.60%). NOEE also inhibited COX-1, COX-2, 5-LO and 12-LO in a highly significant manner. Moreover, acute and sub-acute toxicity studies of NOEE in rats confirm the toxicity with hepatotoxicity at higher doses (2000 mg/kg) i.e. four times greater than the therapeutic dose.ConclusionIt is concluded that crude flower extract of N. oleander is a potent antimicrobial and anti-inflammatory agent with no toxicity potential at therapeutic doses.

Multifunctional Magneto-Plasmonic Fe3O4/Au Nanocomposites: Approaching Magnetophoretically-Enhanced Photothermal Therapy.

Magneto-plasmonic nanocomposites can possess properties inherent to both individual components (iron oxide and gold nanoparticles) and are reported to demonstrate high potential in targeted drug delivery and therapy. Herein, we report on Fe3O4/Au magneto-plasmonic nanocomposites (MPNC) synthesized with the use of amino acid tryptophan via chemical and photochemical reduction of Au ions in the presence of nanosized magnetite. The magnetic field (MF) induced aggregation was accompanied by an increase in the absorption in the near-infrared (NIR) spectral region, which was demonstrated to provide an enhanced photothermal (PT) effect under NIR laser irradiation (at 808 nm). A possibility for therapeutic application of the MPNC was illustrated using cancer cells in vitro. Cultured HeLa cells were treated by MPNC in the presence of MF and without it, following laser irradiation and imaging using confocal laser scanning microscopy. After scanning laser irradiation of the MPNC/MF treated cells, a formation and rise of photothermally-induced microbubbles on the cell surfaces was observed, leading to a damage of the cell membrane and cell destruction. We conclude that the synthesized magneto-plasmonic Fe3O4/Au nanosystems exhibit magnetic field-induced reversible aggregation accompanied by an increase in NIR absorption, allowing for an opportunity to magnetophoretically control and locally enhance a NIR light-induced thermal effect, which holds high promise for the application in photothermal therapy.

Pathophysiological aspects of oxygen, hypoxia and free radical oxidation in critical conditions

Oxygen is the main regulator of metabolic processes in the body not only in the context of normal physiology, but also in the development of various critical conditions.&#x0D; In recent years, the problem of pathogenesis of a number organs' and systems' diseases has been enriched by knowledge of the mechanism of damage to cellular structures. Oxygen turned out to be the main factor of damage the very oxygen, due to the lack of which cell death occurs. It turned out that the so-called reactive oxygen species having an unpaired electron have a biological effect, which, depending on the concentration, can be regulatory or, conversely, toxic. Accordingly, interest has also been aroused in compounds that normally prevent the toxic effect of reactive oxygen species antioxidants. Today it is generally recognized that oxidative stress plays an important and possibly a key role in the pathogenesis of critical conditions. Thus, on the one side, excessive production of free radicals is considered as one of the manifestations of the body's protective reaction to the effects of various environmental factors and living conditions (infections, injuries, toxins, ionizing radiation, physical stress, hypothermia, hypoxia, various types of stress), on the other ― increased production of free radicals quickly leads to irreversible damage: destruction of the erythrocytes' membranes with subsequent hemolysis, transformation of hemoglobin into methemoglobin, DNA damage, desensitization of plasma membrane receptors, inactivation of various hormones and enzymes, including antiradical and antiperoxide protection enzymes.&#x0D; The problem of using oxygen in critical conditions is currently widely discussed in the periodical literature with an emphasis on the oxygen concentrations used in patients, both in operating rooms and in intensive care units. Oxygen used in the intensive care of acute respiratory failure and hypoxia should have a certain concentration range. The toxic effects of oxygen can occur with its prolonged use in high concentrations, which causes not only its direct toxic effect on the lungs, but also in the potentiation of the activation of free radical oxidation and excessive production of reactive oxygen species.&#x0D; The review presents current data on the physiological role of oxygen, its participation in metabolic processes against the background of inflammation, hypoxia and under conditions of activation of free radical oxidation processes. The recent approach to oxygen therapy and the research data presented in the review urge to relate to oxygen as a drug in order to avoid manifestations of its toxic effects.