Biological Defense Mechanisms Research Articles

Lamiales epidermal dynamics: Unveiling antimicrobial resilience in a structural symphony.

This research on Lamiales epidermal anatomy not only provides in-depth understanding of their structural traits but also highlights the significance of uncovering the inherent antimicrobial resilience embedded within these plants. Such insights hold promise for advancing natural product-based approaches in medicine, potentially contributing to the development of novel antimicrobial agents inspired by Lamiales unique biological defense mechanisms. Scanning microscopic tools were utilized to conduct foliar epidermal anatomy of nine species that belong to seven genera and four families within the Lamiales order, Plantaginaceae, Scrophulariaceae, Verbenaceae, and Lamiaceae. This approach aimed to gather both qualitative and quantitative data, facilitating the assessment of taxonomic microanatomical significance. The shape of epidermal cells and their anticlinal walls; number of epidermal cells, stomata, and trichomes; type of stomata and trichomes; length and width of epidermal cells, trichomes, stomatal pore, guard cells, and subsidiary cells; and stomatal index were determined statistically. Most of the species examined were amphistomatous and showed extensive array of trichomes diversity. The exploration of Lamiales epidermal micromorphology and their antimicrobial potential were significant for their implications in multidisciplinary fields. The pharmacological research to utilize sustainable agricultural practices prompts avenues to strengths of Lamiales order for the development of novel antimicrobial solutions and ecological benefits. RESEARCH HIGHLIGHTS: Diverse trichome morphometry reveals a wide array of trichome structures across Lamiales species. Epidermal microscopic architecture variability of epidermal cell shapes and sizes signifies the interspecies variability. Secondary metabolite localization within microanatomical structures elucidates potential hotspots for antimicrobial compound production.

Postharvest Caffeoylquinic Acid Accumulation in Forced Chicory Roots: Insights into the Role of Temperature, Water Loss, and Biological Defense Mechanisms

Postharvest Caffeoylquinic Acid Accumulation in Forced Chicory Roots: Insights into the Role of Temperature, Water Loss, and Biological Defense Mechanisms

Epithelial recognition and elimination against aberrant cells.

Epithelial cells, which are non-immune cells, not only function as a physical defence barrier but also continuously monitor and eliminate aberrant epithelial cells in their vicinity. In other words, it has become evident that epithelial cells possess immune cell-like functions. In fact, recent research has revealed that epithelial cells recognise the Major Histocompatibility Complex I (MHC-I) of aberrant cells as a mechanism for surveillance. This cellular defence mechanism of epithelial cells probably detects aberrant cells more promptly than the conventional immune response, making it a novel and primary biological defence. Furthermore, there is the potential for this new immune-like biological defence mechanism to establish innovative treatment for disease prevention, leading to increasing anticipation for its future medical applications. In this review, we aim to summarise the recognition and attack mechanisms of aberrant cells by epithelial cells in mammals, with a particular focus on the field of cancer. Additionally, we discuss the potential therapeutic applications of epithelial cell-based defence against cancer, including novel prophylactic treatment methods based on molecular mechanisms.

Grapevine histological responses to pruning: the influence of basal buds on tissue defence reactions

Grapevines require pruning procedures to maintain plant morphology and ensure productivity, and these procedures cause wounds that induce physical and biological host defence mechanisms. Grapevine tissue reactions to wounding resulting from four different pruning methods were assessed. Rapid (immediate) defence reactions were detected in 1-year-old canes with preserved basal buds. Formation of tyloses (≈ 90% of xylem vessels) was observed 1 month later on canes where the basal buds were maintained and no short stubs were left (i.e. the pruning cuts preserved the buds). At 2 months after pruning, lignin was slightly increased in cortical parenchyma after pruning of 3-year-old grapevine wood. Neither callose nor suberin production was observed in healing wounds, as is known in other fruit or broadleaf trees. In 3-year-old canes, fungal hyphae were observed in the non-active wood below the pruning cut surfaces. Preliminary observations of desiccation cones within canes confirmed that the basal buds preserved the canes from desiccation, after comparing different pruning procedures on canes of the same age. After 9 months, the desiccation cones were greater in 3- than 1-year-old wounds.

The antioxidant defence of Dekkera bruxellensis against hydrogen peroxide and its relationship to nitrate metabolism.

The yeast Dekkera bruxellensis is a Crabtree-positive yeast that tends towards the oxidative/respiratory metabolism in aerobiosis. However, it is more sensitive to H2O2 than Saccharomyces cerevisiae. In order to investigate this metabolic paradox, the present work aimed to uncover the biological defence mechanism used by this yeast to tolerate the presence of exogenous H2O2. Growth curves and spot tests were performed to establish the values of minimal inhibitory concentration and minimal biocidal concentration of H2O2 for different combinations of carbon and nitrogen sources. Cells in exponential growth phase in different culture conditions were used to measure superoxide and thiols [protein (PT) and non-PT], enzyme activities and gene expression. The combination of glutathione peroxidase (Gpx) and sulfhydryl-containing PT formed the preferred defence mechanism against H2O2, which was more efficiently active under respiratory metabolism. However, the action of this mechanism was suppressed when the cells were metabolizing nitrate (NO3). These results were relevant to figure out the fitness of D. bruxellensis to metabolize industrial substrates containing oxidant molecules, such as molasses and plant hydrolysates, in the presence of a cheaper nitrogen source such as NO3.

The Effect of Combined Treatment of Psilocybin and Eugenol on Lipopolysaccharide-Induced Brain Inflammation in Mice.

Inflammation is an organism's biological defense mechanism. Acute and chronic inflammation of the body triggers the production of pro- and anti-inflammatory pathways that can affect the content of cytokines in the brain and thus cause brain inflammation. Disorders such as depression and posttraumatic stress disorder (PTSD) are often associated with elevated inflammation. Recently, positive and promising clinical results of psilocybin for the treatment of depression and PTSD were reported. Thus, we decided to test whether psilocybin alone or in combination with eugenol, an anti-inflammatory and antioxidant agent, would prevent the increase in or decrease the content of cytokines in the brain of C57BL/6J mice injected with lipopolysaccharides (LPS). Two experiments were performed, one with pre-treatment of mice through gavage with psilocybin (0.88 mg/kg), eugenol (17.6 mg/kg), or combinations of psilocybin and eugenol (1:10, 1:20, or 1:50), followed by intraperitoneal injection of LPS, and the second, post-treatment, with initial injection with LPS, followed by treatment with psilocybin, eugenol, or their combination. Brain tissues were collected, and cytokines were analyzed by qRT-PCR, Western blot, and ELISA. Data were analyzed with a one-way ANOVA followed by Tukey's post hoc test or with multiple unpaired t-tests. LPS upregulated mRNA expression of COX-2, TNF-α, IL-1β, and IL-6. All pre-treatments decreased the expression of COX-2 and TNF-α, with psilocybin alone and in 1:50 combination, with eugenol being the most effective. In the post-treatment, all combinations of psilocybin and eugenol were effective in reducing inflammation, with the 1:50 ratio displaying the most prominent results in reducing the mRNA content of tested cytokines. Western blot analysis confirmed the effect on COX-2 and IL-1β proteins. Finally, the ELISA showed that post-treatment with psilocybin + eugenol (1:50) demonstrated the best results, decreasing the expression of multiple markers including IL-6 and IL-8. This demonstrates the anti-inflammatory effects of a combination of psilocybin and eugenol in the brain of animals with systemically induced inflammation.

ANTI-INFLAMMATORY, ANTIPYRETIC AND ANALGESIC ACTIVITIES OF ETHANOLIC FRUIT EXTRACT MOMORDICA CHARANTIA ON ALBINO RATS

Diverse natural mechanisms against pain, inflammation, and several other infections are varied for medicinal plants. Inflammation is unique biological defense mechanism against harmful stimuli like infections, harmed cells, or irritants. M. charantia is frequently used to treat a variety of illnesses, including fever, discomfort, and inflammation. The purpose of the current study is to identify the anti-inflammatory, antipyretic, and analgesic properties of ethanolic extract of M. charantia. 30 rats were divided into three groups (control, standard and experimental group). Control and standard group contain 5 rats in each group whereas experimental group contained 20 rats. All rats in three groups were treated with carrageenan for induction of oedema, yeast to induce pyrexia and acetic acid to induce pain. Control group rats were treated with normal saline for all the activities. Standard group rats were treated with diclofenac for anti-inflammatory and analgesic activities and paracetamol for antipyretic activity. The fruit extract was injected into abdominal muscles and intraperitoneal tissues.Carrageenan, an anti-inflammatory substance, was used to assess its ability to reduce spell edema, acetic acid was used to study its ability to cause writhing and yeast, was used to demonstrate its ability to pyrexia. The maximal percentage of fruit extract inhibition in anti-inflammatory action was 31.25%. The maximal percentage of fruit extract inhibition against fever was 83.58%. Maximum percentage of inhibition against stomach pain during analgesic action was 31%. Significant findings in anti-inflammatory, antipyretic and analgesic actions were demonstrated at doses of 200 mg/kg, 50 mg/kg, and 100 mg/kg, respectively, when compared to controls. Our research demonstrates and validates the traditional medical usage of M. charantia. It was concluded that ethanolic fruit extract of M. charantia may decrease inflammation, pyrexia and writhing in albino rats effectively.

Will warmer summers increase the impact of UV filters on marine bivalves?

Marine organisms are constantly exposed to multiple stressors including pollutants released into the environment, such as personal care products (PCPs), and climate change-derived factors, namely warming, which are aggravated by anthropogenic drivers and pose increasing pressure on coastal ecosystems. Avobenzone (AVO) is one of the most used ultraviolet (UV) filters in PCPs which have been increasingly used and, thereby, identified in aquatic environments. However, data regarding the influence of warming on the impacts caused by AVO in bivalves is lacking. Mussels are considered good bioindicators thus being often employed in ecotoxicology studies. Hence, the present study aimed to evaluate the toxic effects of an environmentally relevant concentration of AVO (0.5 μg/L) and warming (21 °C), acting alone or in combination, on sperm and adults of the Mediterranean mussel species Mytilus galloprovincialis, through in vitro and in vivo tests, respectively. AVO and warming effects were evaluated by assessing oxidative status, viability, genotoxicity, motility, and kinetics in sperm, together with the quantification of energy content, metabolic capacity, biological defence mechanisms, cellular damage, and neurotoxicity in adults. AVO induced genotoxicity and increased respiration rate in sperm while enhancing the biotransformation enzymes' activity in adults. Exposure to warming led to an increase in respiration rate, ROS overproduction, cellular damage, and viability decrease in sperm whereas metabolic capacity increased in adults. AVO combined with warming caused oxidative stress, cellular damage, genotoxicity, and decreased motility in sperm, while only antioxidant enzymes' activity was enhanced in adults. Overall, the present study demonstrated that when acting in combination the effects of both stressors were more prominent. Furthermore, considering the multiple-stressor scenario tested, major toxic effects occurred in male gametes in comparison to adults.

Oxytocin suppresses CXCL10 production in TNF-α-stimulated human dental pulp stem cells.

Oxytocin (OX) is a posterior pituitary hormone secreted into the blood from axon terminals projecting from the posterior pituitary. Recent reports indicate OX plays an important role in the progression of inflammatory diseases such as rheumatoid arthritis. Pulpitis is caused by the activation of the biological defense mechanism of the dental pulp against cariogenic bacteria. However, the role of OX in the pathogenesis of pulpitis remains unknown. The aim of this study was to examine the effect of OX on CXC chemokine ligand 10 (CXCL10) production in human dental pulp stem cells (HDPSCs). Expression of the oxytocin receptor (OXR) on HDPSCs was detected by Western blot analysis and immunofluorescence. CXCL10 production in HDPSCs was measured using an enzyme-linked immunosorbent assay kit. Western blot analysis was performed to determine the phosphorylation levels of signal transduction molecules, including nuclear factor kappa B, mitogen-activated protein kinases (MAPKs), and Akt in HDPSCs. HDPSCs expressed OXR. OX significantly decreased CXCL10 production in tumor necrosis factor (TNF)-α-stimulated HDPSCs. The p38 MAPK and Akt pathways were related to the OX-suppressed CXCL10 production in TNF-α-stimulated HDPSCs. These results indicate that OX appears to modulate the immune response in pulpitis via suppression of CXCL10 production by HDPSCs.

Oxidative Stress Causes Masculinization of Genetically Female Medaka Without Elevating Cortisol.

Medaka (Oryzias latipes) is a teleost fish with an XX/XY sex determination system. Sex reversal from female-to-male (masculinization of XX fish) can be induced through cortisol elevation from exposure to environmental stress such as high temperature during sexual differentiation. However, the effects of oxidative stress, generated via metabolic reactions and biological defense mechanisms, on the sexual differentiation of medaka are unclear. Here, we investigated the effect of oxidative stress on medaka sexual differentiation using hydrogen peroxide (H2O2), which induces oxidative stress in vertebrates. H2O2 treatment from 0 to 5 days post-hatching induced masculinization of wild-type XX medaka, but not of gonadal soma-derived growth factor (gsdf) or peroxisome proliferator-activated receptor alpha-a (pparaa) knockout XX fish. Co-treatment with an oxidative stress inhibitor caused masculinization recovery but co-treatment with a cortisol synthesis inhibitor did not. H2O2 treatment significantly upregulated gsdf and pparaa expression in XX medaka. However, H2O2 did not elevate cortisol levels in medaka larvae during sexual differentiation. These results strongly indicate that oxidative stress induces masculinization of XX medaka without causing elevation of cortisol.

Countermeasures Against COVID-19 from the Viewpoints of Dental Diseases: Strengthening Innate Immunity with the Toothpick Method of Brushing

Coronavirus disease (COVID-19) patients with periodontal disease have an 8.8-fold higher mortality rate than those in the patients without periodontal diseases. This was higher than the odds ratio for patients with diabetes. Periodontal disease is associated with ulcers in the periodontal pocket, and gram-negative bacteria called periodontal pathogens invade the tissue through ulcers. Bacteria in the ulcer site are phagocytosed and sterilized by leukocytes. Following the autolysis of leukocytes, lipopolysaccharides (LPS) on the bacterial cell wall spread throughout the body, which is a major cause of multiple organ failure. Thus, periodontal disease is considered to contribute to the mortality rate of COVID-19. Ulcers in the periodontal pocket can be repaired using by a new developed brushing method called the toothpick method. The toothpick method can significantly improve gingival bleeding in one week, which is quicker than conventional periodontal treatment methods. Mechanical stimulation by the toothbrush causes gingival basal cells, fibroblasts, vascular endothelial cells and osteoblasts to proliferate and repair the tissue. However, these cell proliferations cease to occur 0.5 mm away from where the toothbrush bristles make contact with the gingiva. The toothpick method of brushing is characterized by its ability to stimulate the interdental gingiva, which is the initial site of periodontitis. As the toothpick method can repair periodontal ulcers, it will strengthen biological defense mechanisms against chronic degenerative and infectious diseases.

Arterial thromboxane A2-induced transient contraction after IL-1β exposure

The involvement of thromboxane A2 (TXA2) in systemic inflammation and infection is well recognized. However, there are few reports on the involvement of prostanoids in warm shock (the initial pathology of sepsis). Previous studies showed that interleukin (IL)-1β causes a rapid inducible nitric oxide synthase/nitric oxide (iNOS/NO)-mediated relaxation in peripheral blood vessels during warm shock. Furthermore, a transient contraction was seen before this relaxation occurred. The present study aimed to elucidate the mechanism of this transient contraction. We measured isometric tension changes in the superior mesenteric arteries from normal male Wistar rats by adding IL-1β at the point of maximum contraction by phenylephrine (Ph). The same study was performed for each vessel pretreated with various inhibitors, including SQ29548, a TXA2 receptor antagonist, 30 min before Ph contraction. In addition, the concentration of thromboxane B2 (TXB2) in SMA was measured by probe electrospray ionization. Treatment of endothelial vessels with cyclooxygenase 1 (COX1)/2 inhibitors SC560/NS398 and TXA2 receptor antagonist SQ29548 suppressed IL-1β–induced transient contractions. This transient contraction reaction was derived from TXA2. Additionally, gene expression of COX2/TXA2 synthetase and the concentration of TXB2 were significantly increased in IL-1β-exposed vessels. It was demonstrated for the first time in inflamed blood vessels that endothelial cell-derived COX2/TXA2 is induced before iNOS and causes transient contractions. TXA2 may be considered an early sign of warm shock or as a biological defense mechanism in the early stages of septic shock.

Seed osmopriming with Ca2+ and K+ improves salt tolerance in quinoa seeds and seedlings by amplifying antioxidant defense and ameliorating the osmotic adjustment process.

Salinity restricts seed germination and seedling growth through induction ofosmotic and oxidative stresses. Therefore, this study aimed to enhance salinity tolerance in quinoa seed by pre-optimized osmo-priming treatments of CaCl2 (10mM, 10°C, 10h) and KNO3 (150mM, 5°C, 24h). The results showed that these treatments developed the cellular defense mechanisms in seeds as 'priming memory' that could improve the physiological and biochemical responses to salinity in post-priming stages. The germination capacity and seedling growth decreased with increasing salinity that was accompanied with a higher content of MDA and H2O2. However, the improvement of primed seed vigor against high salinity was explained by increasing the biological defense mechanisms including antioxidant enzymes (CAT, APX, SOD, GPX and PPO) and antioxidant metabolites (DPPH antioxidant activity, phenolics, flavonoids, ascorbic acid), particularly in presence of salt stress. In addition, Ca2+ and K+ priming acquired salinity tolerance in post-priming stages through a significant increase in the accumulation of proline, glycine-betaine, soluble carbohydrate. Improvement in homeostasis of K+/Na+ ratio by promoting K+ maintenance and Na+ exclusion was also found in post-priming stages. These observations may be utilized as effective methods in improving salinity tolerance of quinoa seed germination in saline agriculture by improving the antioxidant system, osmolyte accumulation and mineral nutrient homeostasis.

Oridonin inhibits SASP by blocking p38 and NF-κB pathways in senescent cells

Cellular senescence is a state of irreversible cell growth arrest that functions as a biological defense mechanism against severe DNA damage. Senescent cells with DNA damage produce pro-inflammatory cytokines, such as IL-6 and IL-8, and this phenomenon is called the senescence-associated secretory phenotype (SASP). SASP factors have been implicated in various disorders, including cancer. We performed a screening assay and identified oridonin as a candidate SASP inhibitor. Oridonin is an active diterpenoid that is isolated from Isodon plants and has been reported to exhibit anti-inflammatory, antibacterial, antioxidant, and antitumor activities. It reduced the secretion of IL-6 and IL-8 in senescent cells at the protein and mRNA levels. Oridonin also inhibited p65 subunit of NF-κB activity. However, oridonin did not affect SA β-gal activity and enhanced the expression of p21. The expression and phosphorylation of p38 were down-regulated by oridonin. The p38 inhibitor SB203580 inhibited the secretion of IL-8, slightly inhibited the secretion of IL-6, and did not affect NF-κB activity. Therefore, the NF-κB and p38 pathways may contribute to the inhibition of SASP by oridonin. Oridonin has potential as a therapeutic agent for SASP-related diseases.

Specialized pro-resolving mediators: biosynthesis and biological role in bacterial infections.

Acute inflammation caused by bacterial infections is an essential biological defence mechanism of the host in order to neutralize and clear the invaders and to return to homeostasis. Despite its protective function, inflammation may become persistent and uncontrolled, resulting in chronic diseases and tissue destruction as consequence of the unresolved inflammatory process. Therefore, spatiotemporal induction of endogenous inflammation resolution programs that govern bacterial clearance as well as tissue repair and regeneration, are of major importance in order to enable tissues to restore functions. Lipid mediators that are de-novo biosynthesized from polyunsaturated fatty acids (PUFAs) mainly by lipoxygenases and cyclooxygenases, critically regulate the initiation, the maintenance but also the resolution of infectious inflammation and tissue regeneration. The discovery of specialized pro-resolving mediators (SPMs) generated from omega-3 PUFAs stimulated intensive research in inflammation resolution, especially in infectious inflammation elicited by bacteria. SPMs are immunoresolvents that actively terminate inflammation by limiting neutrophil influx, stimulating phagocytosis, bacterial killing and clearance as well as efferocytosis of apoptotic neutrophils and cellular debris by macrophages. Moreover, SPMs prevent collateral tissue damage, promote tissue repair and regeneration and lower antibiotic requirement. Here, we review the biosynthesis of SPMs in bacterial infections and cover specific mechanisms of SPMs that govern the resolution of bacteria-initiated inflammation.

Molecular Hydrogen as a Novel Antitumor Agent: Possible Mechanisms Underlying Gene Expression.

While many antitumor drugs have yielded unsatisfactory therapeutic results, drugs are one of the most prevalent therapeutic measures for the treatment of cancer. The development of cancer largely results from mutations in nuclear DNA, as well as from those in mitochondrial DNA (mtDNA). Molecular hydrogen (H2), an inert molecule, can scavenge hydroxyl radicals (·OH), which are known to be the strongest oxidizing reactive oxygen species (ROS) in the body that causes these DNA mutations. It has been reported that H2 has no side effects, unlike conventional antitumor drugs, and that it is effective against many diseases caused by oxidative stress and chronic inflammation. Recently, there has been an increasing number of papers on the efficacy of H2 against cancer and its effects in mitigating the side effects of cancer treatment. In this review, we demonstrate the efficacy and safety of H2 as a novel antitumor agent and show that its mechanisms may not only involve the direct scavenging of ·OH, but also other indirect biological defense mechanisms via the regulation of gene expression.

Strategy for understanding the biological defense mechanism involved in immune priming in kuruma shrimp

Since the 1970s, individuals that survive a specific infectious disease among crustaceans reportedly develop resistance to the given virulence factors. Quasi-immune response is a similar phenomenon of acquired resistance against white spot syndrome virus, also found in kuruma shrimp. This phenomenon, resembling immunological memory, is collectively called immune priming and recently attracts increasing attention. In this study, I review, along with recent findings, past attempts to immunize shrimp by administration of the pathogen itself or recombinant proteins of viral constituent factors. Moreover, I aimed at investigating the diversity of pattern recognition receptors in kuruma shrimp from the currently available information that allows for a better understanding of immune priming. This review would potentially help to elucidate the underlying mechanisms of immune priming in the future.

Sigara İçenlerde Serum Nikel, Silisyum, Arsenik ve Bor Analizi

Smoking induces inflammation and oxidative stress via radical production from chemicals resulting in cardiocerebrovascular and respiratory diseases, cancers, stroke and sudden death. Elements found in tobacco plant and tobacco smoke are absorbed into blood circulation and transferred into blood and peripheral tissues. The aim of the present study is to evaluate the alterations of serum nickel (Ni), silicium (Si), arsenic (As) and boron (B) levels in smokers. The study groups were categorized as individuals who quitted smoking (Group 1; n: 35; 15 female/20 male), who were smoking (Group 2; n:35; 13 female, 22 male) and who never-smoked (Group 3; n; 40; 20 female/20 male). Biochemical parameters were analyzed in Biochemistry Laboratory of Haseki Traning and Research Hospital. Serum element levels were measured using Inductively Coupled Plasma Atomic Emission Spectroscopy in Trace Element Laboratory of Biophysics Department of Cerrahpasa Medical Faculty at Istanbul University-Cerrahpasa. ANOVA test and Pearson’s correlation tests were used for statistical analysis and p < 0.05 was evaluated as statistically significant. Serum Ni levels of Group 2 were higher than the other study groups with no significance. Group 2 had statistically higher serum Si and As levels than Group 1 and Group 3 (p < 0.01, p < 0.05, respectively). There was no statistical significance by means of serum B levels among study groups. Increased serum levels of Si and As in smokers might induce atherosclerosis via inflammation, dyslipidemia and burden oxidative stress. Besides, higher serum Ni levels of smokers might reflect its toxic effects. However, serum B was lower in smokers probably related with its consumption in biological defence mechanisms. Monitorization of serum nickel, silicium, arsenic and boron levels should be considered as biomarkers for smokers.

Abstract P9: Mid-Regional Pro-Adrenomedullin as a Novel Biomarker of Transient Ischemic Attack

Background: Transient ischemic attack (TIA) is often a warning sign for ischemic stroke within a couple of months and should be treated as an emergency disease. However, the symptoms often disappear within a few hours, making the diagnosis of TIA difficult. The peptide hormone adrenomedullin (AM) increases during the acute phase of ischemic stroke because AM is produced by vascular endothelial cells as a biological defense mechanism against hypoxia and oxidative stress during cerebral ischemia. Therefore, we hypothesized that the blood levels of mid-regional pro-adrenomedullin (MR-pro-AM), half-life of which is several hours and much longer than AM, in patients with TIA could be a useful biomarker for the diagnosis of TIA. Method: We retrospectively compared the blood levels of MR-pro-AM using stored peripheral blood samples of the TIA cohort within 14 days from onset in the National Cerebral and Cardiovascular Center from April 1, 2016 to March 30, 2019, and those of the population-based cohort of the Kyoto Prefectural University of Medicine. Results: The TIA cohort (n = 39) was significantly older (73 vs. 58 years old) and showed higher frequency of cerebrovascular risk factors and higher levels of MR-pro-AM (0.584 vs. 0.418 nmol/l) than the population-based cohort (n = 1298). The MR-pro-AM level was significantly associated with TIA: odds ratio (OR) per 0.1 nmol/l MR-pro-AM increment was 2.8 (95% confidence interval (CI) = 2.2-3.6) in univariable analysis and 1.5 (95% CI = 1.1-2.1) in multivariable analysis with sex, age, chronic kidney disease and cerebrovascular risk factors as covariates. The cutoff value of MR-pro-AM was 0.523 nmol/l based on receiver operating characteristic curve analysis for TIA, with a sensitivity of 69% and a specificity of 88% (area under the curve = 0.78). Moreover, the model with the blood level of MR-pro-AM in addition to the prediction model the ABCD 2 score predicted TIA more accurately (net reclassification improvement = 1.14, p &lt; 0.001). The MR-pro-AM level was found significantly higher in the TIA cohort than the population-based cohort after propensity score-matching (0.665 vs. 0.525 nmol/l, p = 0.047). Conclusion: MR-pro-AM may be a promising diagnostic biomarker for TIA.

16216 Fernblock promotes antioxidant defence systems in environmentally stressed human keratinocytes (UV, pollution) via Nrf2 pathway induction

The skin is the most important defensive barrier of our body to protect us against environmental damage. It is well known that exposure to ultraviolet (UV) sun radiation leads to oxidative stress, photoaging, and photocarcinogenesis. However, more recently, research highlights the importance of environmental pollution damage to the skin, and how solar radiation can synergically interact with ubiquitous environmental pollutants to further increase hyperpigmentation, skin aging or cancer. In response, skin cells use biological defense mechanisms to reverse these deleterious actions.