Co-exposure effect of different colour of LED lights and increasing temperature on zebrafish larvae (Danio rerio): Immunohistochemical, metabolomics, molecular and behaviour approaches.

Although there are studies in the literature on the effects of different coloured light-emitting diodes (LEDs) on different organisms, there is limited information on how these effects change with temperature increase. In this study, the effects of blue, green, red and white LED lights on the early development process of zebrafish (Danio rerio (Hamilton, 1822)) were comprehensively investigated. In addition, to simulate global warming, it was examined how a one-degree temperature increase affects this process. For this purpose, zebrafish embryos, which were placed at 4 hpf (hours post fertilization) in an incubator whose interior was divided into four areas, were kept at three different temperatures (28, 29 and 30 °C) for 120 h. The group kept in a dark environment was chosen as the control. The temperature of the control group was also increased at the same rate as the other groups. The results showed that at the end of the exposure period, temperature and light colour caused an increase in body malformations. Histopathological damage and immunopositive signals of HSP 70 and 8-OHdG biomarkers in larval brains, increase in free oxygen radicals, apoptotic cells and lipid accumulation throughout the body, increase in locomotor activity, decrease in heart rate and blood flow, and significant changes in more than thirty metabolite levels were detected. In addition, it has been determined that many metabolic pathways are affected, especially glutathione, vitamin B6 and pyrimidine metabolism. Moreover, it has been observed that a one-degree temperature increase worsens this negative effect. It was concluded that blue light was the closest light to the control group and was less harmful than other light colours. The study revealed that blue light produced results that were most similar to those seen in the control group.

Understanding the side effects of chronic silodosin administration via untargeted metabolomics approach.

BACKGROUND: Precision medicine, which looks for high efficacy and low toxicity in therapies, has increased in popularity with omics technology. This work aims to discover novel and low-toxicity therapy options by examining the complex relationship between silodosin-induced side effects and the metabolomic profiles associated with its administration. MATERIALS AND METHODS: The plasma samples of the control group and silodosin-treated rats were analyzed by LC-Q-TOF-MS/MS. Employing XCMS and MetaboAnalyst software, MS/MS data processed to detect compounds and investigate metabolic pathways. MATLAB 2019b was used for data categorization and multivariate analysis. A thorough comparison of METLIN and HMDB databases revealed 41m/z values with significant differences between the drug-treated and control groups (p <0.01 and fold analysis≥1.5). RESULTS: According to multivariate data analysis, 17-ß-estradiol, taurocholic acid, L-kynurenine, N-formylkynurenine, D-glutamine, L-arginine, prostaglandin H2, prostaglandine G2, 15-keto-prostaglandin E2, calcidiol, thromboxane A2, 5'-methylthioadenosine, L-methionine and S-adenosylmethionine levels changed significantly compared to the control group. Differences in the metabolisms of glycerophospholipid, tyrosine, phenylalanine, arachidonic acid, cysteine and methionine, and biosynthesis of phenylalanine, tyrosine, and tryptophan, and aminoacyl-tRNA have been successfully demonstrated by metabolic pathway analysis. According to this study, vitamin D, D-glutamine, and L-arginine supplements can be recommended to prevent side effects such as fatigue, intraoperative floppy iris syndrome, blurred vision, and dizziness in the treatment of silodosin. Silodosin treatment negatively affected the immune system by affecting the kynurenine and tryptophan metabolism pathways. CONCLUSIONS: The study is a guide for silodosin treatments that offer low side effects and high therapeutic effect within the scope of precision medicine.

LUNGBANK: a novel biorepository strategy tailored for comprehensive multiomics analysis and P-medicine applications in lung cancer.

Background/aim: LUNGBANK was established as part of Project LUNGMARK, pioneering a biorepository dedicated exclusively to lung cancer research. It employs cutting-edge technologies to streamline the handling of biospecimens, ensuring the acquisition of high-quality samples. This infrastructure is fortified with robust data management capabilities, enabling seamless integration of diverse datasets. LUNGBANK functions not merely as a repository but as a sophisticated platform crucial for advancing lung cancer research, poised to facilitate significant discoveries. Materials and methods: LUNGBANK was meticulously designed to optimize every stage of biospecimen handling, from collection and storage to processing. Rigorous standard operating procedures and stringent quality control measures guarantee the integrity of collected biospecimens. Advanced data management protocols facilitate the efficient integration and analysis of various datasets, enhancing the depth and breadth of research possibilities in lung cancer. Results: LUNGBANK has amassed a comprehensive collection of biospecimens essential for unraveling the intricate molecular mechanisms of lung cancer. The integration of state-of-the-art technologies ensures the acquisition of top-tier data, fostering breakthroughs in translational and histological research. Moreover, the establishment of patient-derived systems by LUNGBANK underscores its pivotal role in personalized medicine approaches. Conclusion: The establishment of LUNGBANK marks a significant milestone in addressing the critical challenges of lung cancer research. By providing researchers with high-quality biospecimens and advanced research tools, LUNGBANK not only supports Project LUNGMARK's objectives but also contributes extensively to the broader landscape of personalized medicine. It promises to enhance our understanding of lung cancer initiation, progression, and therapeutic interventions tailored to individual patient needs, thereby advancing the field towards more effective diagnostic and therapeutic strategies.

Investigating the pathogenesis of vitreous in postmortem COVID patients via untargeted metabolomics based bioinformatics model.

SARS-CoV-2 virus has become a worldwide pandemic causing millions of death. This severe disaster lead to a immense panic and stress all over the world. Several studies were dedicated to understand its mechanism, pathogenesis and spreading characteristics. By this way, scientists try to develop different therapy and diagnose strategies. For these reasons, several metabolomics, proteomics and genomics studies were also carried out to improve knowledge in this newly identified virus. In this study, we are aimed to explain the pathogenesis of SARS-CoV-2 exposure on postmortem COVID (+) patients via untargeted metabolomics analysis. To carry out this study, a Data Independent Acquisition SWATH method is optimized and performed. Vitreous samples were analyzed in both MS1 and MS2 ESI(+) mode. An orthogonal Partial Least Square Discriminant Analysis were performed for classification. It was observed that lipid metabolism, several amino acids and oxidative stress biomarkers were strongly affected due to high inflammation and possible cytokine storm.

Analyzing the impact of synthetic and natural steroids: a study of cytochrome P450 metabolism, morphological alterations through metabolomics, and histopathological Examination.

This study focuses on the comparative metabolic profiling and effects of two steroid types: natural and synthetic, specifically 17α-methyl testosterone (17α-MT) at varying concentrations (1.5, 2, and 3 mg/kg) in rainbow trout (Oncorhynchus mykiss). Over a 75-day feeding trial, growth metrics, such as feed efficiency, daily specific growth, live weight gain, total weight gain, and survival rate were systematically monitored every 15 days. At the end of the feeding trial, histopathology, immunohistochemistry, and metabolome analyses were performed in the high-concentration groups (3 mg/kg natural and 3 mg/kg synthetic), in which the lowest survival rate was determined. Key findings reveal that the type of hormone significantly influences growth parameters. While some natural steroids enhanced certain growth aspects, synthetic variants often yielded better results. The metabolomic analysis highlighted significant shifts in the metabolism of tryptophan, purine, folate, primary bile acids, phosphonates, phosphinates, and xenobiotics via cytochrome P450 pathways. Histopathologically, the natural hormone groups showed similar testicular, hepatic, muscular, gill, cerebral, renal, and intestinal tissue structures to the control, with minor DNA damage and apoptosis observed through immunohistochemistry. Conversely, the synthetic hormone groups exhibited moderate DNA damage and mild degenerative and necrotic changes in histopathology.

Dysregulated Leukotriene Metabolism in Patients with COVID-19.

This study aimed to examine the leukotriene metabolism during COVID-19. In total, 180 participants were included in this study, of which 60 were healthy controls, 60 required intensive care units (ICU), and 60 did not require intensive care (non-ICU). The serum levels of 5-lipoxygenase (5-LO), 5-LO activating protein (ALOX5AP), and cysteinyl leukotriene (CYSLT) were measured, and the mRNA expression levels of 5-LO, ALOX5AP, and cysteinyl leukotriene receptor 1 (CYSLTR1) were investigated. Compared with the control group, both the non-ICU and ICU groups had lower levels of 5-LO and mRNA expression. ICU patients had lower levels of 5-LO and mRNA expression than non-ICU patients. CYSLTR1 mRNA expression was highest in the ICU group, followed by the non-ICU group, and healthy controls had the lowest mRNA expression levels. CYSLT levels were higher in the control group than in the non-ICU and ICU groups. CYSLTR1 expression was higher in patients than in controls; therefore, selective leukotriene receptor blockers can be used as treatment options. CYSLTR1 expression was higher in the ICU group than in the non-ICU group. Furthermore, CYSLTR1 mRNA expression may be a promising biomarker of COVID-19 severity.

Evaluating Alterations in Breast Cancer Patients after Recovery Via A PET/CT-Assisted Metabolomics Approach.

OBJECTIVE: Breast cancer is a mortal disease that causes many deaths, especially in women. Improved therapies could contribute positively to survival rates. Metabolomics is an important tool for monitoring the alterations of several metabolites in clinical cases. This study aimed to develop a metabolomics model to observe (via mass spectroscopy) metabolic alterations in patients who suffered from breast cancer (BC), both before and after their recovery. MATERIALS AND METHODS: Grades 1 and 2 invasive ductal carcinoma patients were evaluated based on their positron emission tomography/computed tomography results. Fourteen patients who had fully recovered from BC were subjected to metabolomics analysis. Plasma samples were extracted and analyzed via quadrupole time-of-flight mass tandem spectroscopy. A chemometrics analysis was performed in order to determine the statistically significant metabolites. All the metabolites were annotated via the mummichog algorithm. RESULTS AND DISCUSSION: According to the data analysis, glucose, ornithine, phenyalanine, some vitamins, and metabolites in the fatty acid metabolism were statistically altered after recovery of each patient. CONCLUSION: Untargeted metabolomics studies can be used to understand the etiopathogenesis of breast cancer, finding new biomarkers and alterations of metabolic pathways. After the tumor burden was removed, homeostasis was restored and the concentration of several metabolites began to normalize. This study elucidated the effects of breast cancer at the molecular level.

Global warming and nanoplastic toxicity; small temperature increases can make gill and liver toxicity more dramatic, which affects fillet quality caused by polystyrene nanoplastics in the adult zebrafish model.

Increasing nanoplastics (NPs) pollution may lead to unknown environmental risks when considered together with climate change, which has the potential to become an increasingly important environmental issue in the coming decades. In this context, the present study aimed to evaluate the stressor modelling of polystyrene nanoplastic (PS-NPs) combined with temperature increase in zebrafish. For this purpose, changes in gill, liver and muscle tissues of zebrafish exposed to PS-NPs (25 ppm) and/or different temperatures (28, 29 and 30 °C) for 96 h under static conditions were evaluated. The results obtained emphasize that exposure to PS-NPs stressors under controlled conditions with temperature increase induces DNA damage through stress-induced responses accompanied by degeneration, necrosis and hyperaemia in zebrafish liver and adhesion of lamellae, desquamation and inflammation in lamellar epithelium in gills. Metabolomic analyses also supported changes indicating protein and lipid oxidation, especially PS-NPs-mediated. These findings will contribute to the literature as key data on the effects of PS-NPs presence on protein/lipid oxidation and fillet quality in muscle tissues.

Antioxidant/protective effects of carob pod (Ceratonia siliqua L.) water extract against deltamethrin-induced oxidative stress/toxicity in zebrafish larvae.

In our study, the antioxidant capacity of carob pods water extract (CPWE) against deltamethrin (DM)-induced oxidative stress, a widely used pesticide around the world, was investigated in vitro and in vivo in a zebrafish model. The in vitro antioxidant capacity of the obtained extract was evaluated with different methods using trolox, BHA and BHT standard antioxidants. For in vivo experiments, 4hpf zebrafish embryos were exposed to 10 ppb and 25 ppb DM for 120 h and the larvae were treated with 1-10 and 100 ppm CPWE for 4 h at 72th hours. According to the results obtained, it has been determined that the exposure of zebrafish to DM during the developmental period causes important body malformations, decrease in survival rate, reduction in eye size, shortening in body length and decrease in locomotor activity in the dark period. In addition, according to the results of whole-mount staining, it was determined that DM caused a significant increase in the amount of free oxygen radicals and apoptotic cells. It was also confirmed by metabolome analysis that CPWE application for 4 h reduced DM-induced toxicity and oxidative stress. As a result, it can be said that CPWE has an important antioxidant capacity in eliminating DM-induced oxidative stress.

Global warming and glyphosate toxicity (I): Adult zebrafish modelling with behavioural, immunohistochemical and metabolomic approaches.

Global warming further increases the toxic threat of environmental pollutants on organisms. In order to reveal the dimensions of this threat more clearly, it is of great importance that the studies be carried out with temperature differences as close as possible to the temperature values that will represent the global climate projection. In our study, how the toxicity of glyphosate, which is widely used around the world, on zebrafish changes with temperature increases of 0.5° was investigated on behavioral and molecular basis. For this purpose, adult zebrafish were exposed to glyphosate at concentrations of 1 ppm and 5 ppm for 96 h in four environments with a temperature difference of 0.5° (28.5; 29.0; 29.5; 30.0 °C). At the end of the exposure, half of the zebrafish were sampled and remaining half were left for a 10-day recovery process. At the end of the trials, zebrafish were subjected to circadian rhythm and anxiety tests. In addition, histopathological, immunohistochemical and metabolome analyses were performed on brain tissues. As a result, it has been detected that anxiety and circadian rhythm were disrupted in parallel with the increased temperature and glyphosate concentration, and increased histopathological findings and 5-HT4R and GNAT2 immunopositivity in the brain. As a result of metabolome analysis, more than thirty annotated metabolites have been determined due to the synergistic effect of temperature increase and glyphosate exposure. As a conclusion, it was concluded that even a temperature increase of 0.5° caused an increasing effect of glyphosate toxicity in the zebrafish model.

Chemometrics assisted untargeted metabolomic analysis to explore metabolic alterations in chronic urticaria via LC/Q-TOF/MS/MS.

Chronic urticaria (CU) is a common disease characterized by the development of recurrent itchy blisters and/or angioedema lasting longer than 6 weeks. The evidence-based diagnosis of CU is described in the most recent urticaria guideline. Metabolomics has the potential to offer diagnostic biomarkers for the detection and prognosis of diseases and predict the efficacy and safety of pharmaceutical interventions. Determining the variation in metabolites found in the plasma of CU patients (n = 20) and 20 controls has therefore been the goal of this investigation. Samples were analyzed using liquid chromatography quadrupole time-of-flight mass spectrometry after applying acetonitrile precipitation. For the purpose of identifying and characterizing metabolites, the METLIN database was utilized. According to results, 21 metabolites were found to be significantly (VIP score > 0.7, p < .05 and fold analysis >1.5) altered. Differentiations between each group were successful via both OPLS-DA and ROC analysis. While plasma allantoate, homogentisate, indole acetate, proline, phenylalanine levels decreased in CU patients compared to healthy subjects, tryptophan, spermidine, phenyl pyruvate, oleic acid, lysine, valine, ornithine, histidine, glutamate, leucine, kynurenine, hypoxanthine, tyrosine, glucose, creatine and cortisol levels were significantly increased. Diagnosis of CU could be achieved by evaluating the metabolic profile of patients.

Metabolomic profiling in ankylosing spondylitis using time-of-flight mass spectrometry.

BACKGROUND & AIMS: Ankylosing spondylitis (AS) is an inflammatory disease associated with destructive changes in the skeleton and joints. The exact molecular mechanism of the disease has not been fully elucidated. This study aimed to determine metabolic differences between active AS patients and healthy controls to understand the molecular mechanism of AS. PATIENTS AND METHODS: The study included 38 subjects, comprising 18 patients with active AS and 20 healthy controls. Metabolic profiling of the plasma was performed using ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC Q-TOF/MS). Data acquisition, classification, and identification were achieved with the METLIN (https://metlin.scripps.edu/) database and XCMS (https://xcmsonline.scripps.edu). RESULTS: Significant alterations were identified in the unsaturated fatty acids (FA), linoleic acid, alpha-linolenic acid, FA degradation, and FA biosynthesis pathways. Down -regulations were observed in phosphatidylcholine (PC) (16:0/0:0), beta-d-Fructose, stearic acid, trimipramine N-Oxide and muconic acid, and up-regulation were detected in PC (18:2/0:0), 3-Methylindole, palmitic acid (PA), alpha-Tocotrienol, and beta-d-glucopyranoside in active AS patients compared to the healthy control subjects. CONCLUSION: Pathway analysis revealed that dysregulation in FA metabolism is associated with AS, and therefore, modulation of diet according to PA and PC may be potential therapeutic targets.

Nano-sized polystyrene plastic particles affect many cancer-related biological processes even in the next generations; zebrafish modeling.

With the ever-increasing plastic pollution, the nano-sized plastic particles that are constantly released from the main materials have a greater potential threat. Studies continue on how to eliminate plastic waste, which has become a global problem, from nature. We are aware that complete elimination is not easy at all, but it is not known clearly that even if it is successful, its effects on organisms will also disappear completely. In this study, zebrafish injected with 20 nm-sized polystyrene particles (PS) only during the embryonic period were grown in an environment without plastic exposure. The effects of PS on their offspring embryo/larvae were examined at morphological, molecular and metabolomic levels. Results showed that parental PNP exposure caused significant malformations, decreased survival rate, increased heart rate and blood flow rate, as well as decreased eye size, height and locomotor activity, which were attributed to growth retardation in the offspring. According to the results of whole-mount immunofluorescence larval staining, cell death and reactive oxygen species were significantly increased, while lipid accumulation was decreased in new generation larvae from zebrafish injected with PNP. In order to elucidate the mechanisms underlying these morphological, physiological and molecular damages, the metabolome analyses were performed by evaluating the Q-TOF MS/MS spectra with chemometric analyses in the offspring larvae. According to the metabolomics results, 28 annotated metabolomes suggested by the OPLS-DA analysis that may vary significantly through a variable in projection scores were detected. In addition, it was detected that the significantly increased histopathological findings and immunopositivity of JNK, H2A.X, PI3 and NOP10 in new generation larvae. In conclusion, it has been shown that exposure to PS, even only during the embryonic period, may affect many cancer-related biological processes in the next generation.

Effects of the food colorant carmoisine on zebrafish embryos at a wide range of concentrations.

Since the middle of the twentieth century, the use of dyes has become more common in every food group as well as in the pharmaceutical, textile and cosmetic industries. Azo dyes, including carmoisine, are the most important of the dye classes with the widest color range. In this study, the effects of carmoisine exposure on the embryonic development of zebrafish at a wide dose scale, including recommended and overexposure doses (from 4 to 2000 ppm), were investigated in detail. For this purpose, many morphological and physiological parameters were examined in zebrafish exposed to carmoisine at determined doses for 96 h, and the mechanisms of action of the changes in these parameters were tried to be clarified with the metabolite levels determined. The no observed effect concentration (NOEC) and median lethal concentration (LC50) were recorded at 5 ppm and 1230.53 ppm dose at 96 hpf, respectively. As a result, it was determined that the applied carmoisine caused serious malformations, reduction in height and eye diameter, increase in the number of free oxygen radicals, in apoptotic cells and in lipid accumulation, decrease in locomotor activity depending on the dose and at the highest dose, decrease in blood flow rate. In the metabolome analysis performed to elucidate the metabolism underlying all these changes, 45 annotated metabolites were detected.

The synergic toxicity of temperature increases and nanopolystrene on zebrafish brain implies that global warming may worsen the current risk based on plastic debris.

Global warming and plastic pollution are among the most important environmental problems today. Unfortunately, our world is warming more than expected and biological life, especially in the oceans, has come to the limit of the struggle for survival with the nano-scale plastic pollution that is constantly released from the main material. In this study, the synergic effect of one-degree temperature increase (28, 29, 30 °C) and 100 nm size polystyrene plastic nanoparticles on circadian rhythm, brain damage and metabolomics in zebrafish were investigated in an environment where temperature control with 0.05-degree precision is provided. A temperature increase of 1°, together with nanoplastic exposure, affected the circadian rhythm in zebrafish, caused damage to the brain and caused significant changes in the intensity of a total of 18 metabolites in different pathways. It was also detected Raman signals of polystyrene in the brain homogenate. As a consequence, it is suggested that one degree of temperature increase pave the way for degeneration in the brain by disrupting some metabolic pathways, thereby significantly increasing the negative effects of nano-plastic on behavior.

A comprehensive study to evaluate the wound healing potential of okra (Abelmoschus esculentus) fruit.

ETHNOPHARMACOLOGICAL RELEVANCE: Okra fruit (Abelmoschus esculentus (L.) Moench) has been extensively used for the treatment of skin damage and subcutaneous tissue abscess for many years in Turkish folk medicine. AIM OF STUDY: In this study, we aimed to investigate the wound healing potential of okra fruit by in vitro and in vivo experimental models in detail. Furthermore, based on the results of experiments, a wound healing formulation was developed and its activity profile was studied. MATERIALS AND METHODS: For this purpose, the phenolic, flavonoid and proanthocyanidin contents and chemical profile of aqueous and ethanolic extracts prepared from okra fruits cultivated in two different locations of Turkey, i.e. Aegean and Kilis regions, were comparatively determined and the tryptophan levels, which is known to be an influential factor in wound healing, were measured. Antioxidant activity of the okra fruit extracts was determined by DPPH test, ABTS radical scavenger activity, iron-binding capacity, total antioxidant capacity and copper reduction capacity assays. Moreover, antibacterial activity potentials of the aqueous and ethanolic extracts of okra fruits were determined. The protective effect of the extracts against H2O2-induced oxidative stress and anti-inflammatory activity were assessed in HDF (human dermal fibroblast) cells and in RAW 264.7 murine macrophages, respectively. The biocompatibility of the gel formulations prepared with the best performing extract were evaluated by human Epiderm™ reconstituted skin irritation test model. Wound-healing activity was investigated in rats by in vivo excision model and, histopathological examination of tissues and gene expression levels of inflammation markers were also determined. RESULTS: According to our findings, the aqueous and ethanolic extracts of okra fruits were found to possess a rich in phenolic content. Besides, isoquercitrin was found to be a marker component in ethanolic extracts of okra fruits. Both extracts exhibited antioxidant activity with significant protective effect against H2O2-induced damage in HDF cells by diminishing the MDA level. Also, the highest dose of ethanolic extracts has displayed a potent anti-inflammatory activity on LPS-induced RAW264.7 cells. Besides, both water and ethanolic extracts were shown to possess antimicrobial activity. On the other hand, the formulations prepared from the extracts were found non-irritant on in vitro Epiderm™-SIT. In vivo excision assay showed that tissue TGF-ß and IL-1ß levels were significantly decreased by the 5% okra ethanolic gel formulation. The histopathological analysis also demonstrated that collagenisation and granulation tissue maturation were found higher in 5% (w/v) okra ethanolic extract-treated group. CONCLUSION: 5% of okra ethanolic extract might be suggested as a potent wound healing agent based on the antimicrobial, antioxidant and anti-inflammatory tests. The proposed activity was also confirmed by the histopathological findings and gene expression analysis.

Evaluation of anticholinesterase effect of some Epilobium species and quantification of hyperoside by HPLC.

This article presents the evaluation of anticholinesterase effects of aerial parts of Epilobium angustifolium, E. stevenii and E. hirsutum and isolated flavonoids from E. angustifolium, and quantification of the flavonoids by HPLC. Besides, the highest acetylcholinesterase inhibition was seen in the EtOAc sub-extracts of E. angustifolium and E. stevenii (36.51 ± 1.88 and 39.89 ± 3.09%, respectively), whereas EtOAc sub-extract of E. angustifolium had the best butyrylcholinesterase inhibition (62.09 ± 1.98%). Hyperoside showed strong inhibition activity on both enzymes. The active EtOAc sub-extract of E. angustifolium was quantitatively analyzed for their content of hyperoside (quercetin-3-O-ß-D-galactoside) by HPLC. The content of hyperoside in EtOAc sub-extract of E. angustifolium was detected as 3.312%. The anatomical structures of the stem, leaf, sepal, petal, anther, and filament of E. angustifolium were investigated. The anatomical properties given in this study provide a description of E. angustifolium.[Formula: see text].

Metabolomics approach: Interpretation of changes in rat plasma metabolites after solifenacin treatment

Abstract Changes in metabolite levels of patients using the long-term drug can be comprehensively demonstrated by pharmacometabolomic studies. In this study, biological alterations induced by the administration of solifenacin succinate were investigated with a pharmacometabolomics approach on rat metabolism. Plasma samples obtained from rats were analyzed by LC-Q- TOF/MS/MS. METLIN and HMDB databases were used to identify metabolites. Data were processed and classified with MATLAB 2017b. 53 m/z values were found to be significantly different between the drug and control groups (p ≤ 0.01 and fold analysis > 1.5) and identified by comparing METLIN and HMDB databases. According to multivariate data analysis, changes in arachidonic acid, thromboxane A2, palmitic acid, choline, calcitriol, histamine phosphate, retinyl ester, l-cysteine, l-leucine, beta-alanine, l-histidine levels were found to be statistically significant compare to the control group. Differences in the biosynthesis of phenylalanine, aminoacyl-tRNA, tyrosine, tryptophan, metabolism of glycerophospholipid, cysteine, methionine, histidine, arachidonic metabolism have been successfully demonstrated by the metabolomics approach. Our study provides important information to explain the efficacy and toxicity of chronic administration of solifenacin succinate

New bone cements with Pluronic®F127 for prophylaxis and treatment of periprosthetic joint infections.

In line with the increase in orthopedic prosthetic surgeries, there has been a significant rise in periprosthetic joint infections (PJI) due to Methicillin-Resistant Staphylococcus Aureus (MRSA) bacteria. In case of infection, antibiotic-added spacers are temporarily placed into the periprosthetic region. With the release of antibiotics usually failing to work in fighting off infection, recent studies have centered around developing more effective approaches. New polymethylmethacrylate (PMMA) cement mixtures were prepared for this study with Pluronic®F127, bicarbonate, and citric acid addition. Optimal solutions were searched by monitoring vancomycin release on consecutive days with HPLC in in-vitro. The strengths of the samples were measured via four-point bending tests. Compared to conventional PMMA, strength values were observed to have improved by about 20% with 1.0 g of Pluronic®F127. According to HPLC studies, the highest increase for the area under the curve value was obtained for Pluronic®F127 doped mixture with a value of about 20%. It is understood from SEM and BET studies that addition of Pluronic®F127 helps increase porosity. The present study concludes that the optimum concentration of Pluronic®F127 could improve the strength and drug-releasing capacity of the spacer by increasing its porosity.