Layer-by-layer assembly of chitosan/alginate thin films containing Salmonella enterica bacteriophages for antibacterial applications.

The emergence of antibiotic resistant bacteria and the ineffectiveness of routine treatments inspired development of alternatives to biocides for antibacterial applications. Bacteriophages are natural predators of bacteria and are promising alternatives to antibiotics. This study presents fabrication of a Salmonella enterica bacteriophage containing ultra-thin multilayer film composed of chitosan and alginate and demonstrates its potential as an antibacterial coating for food packaging applications. Chitosan/alginate film was prepared through layer-by-layer (LbL) self-assembly technique. A bacteriophage, which belongs to Siphoviridae morphotype (MET P1-001_43) and infects Salmonella enterica subsp. enterica serovar Enteritidis (Salmonella Enteritidis), was post-loaded into chitosan/alginate film. The LbL growth, stability, and surface morphology of chitosan/alginate film as well as phage deposition into multilayers were analysed through ellipsometry, QCM-D and AFM techniques. The bacteriophage containing multilayers showed antibacterial activity at pH 7.0. In contrast, anti-bacterial activity was not observed at acidic conditions. We showed that wrapping a Salmonella Enteritidis contaminated chicken piece with aluminium foil whose surface was modified with phage loaded chitosan/alginate multilayers decreased the number of colonies on the chicken meat, and it was as effective as treating the meat directly with phage solution.

TW68, cryptochromes stabilizer, regulates fasting blood glucose levels in diabetic ob/ob and high fat-diet-induced obese mice.

Cryptochromes (CRYs), transcriptional repressors of the circadian clock in mammals, inhibit cAMP production when glucagon activates G-protein coupled receptors. Therefore, molecules that modulate CRYs have the potential to regulate gluconeogenesis. In this study, we discovered a new molecule called TW68 that interacts with the primary pockets of mammalian CRY1/2, leading to reduced ubiquitination levels and increased stability. In cell-based circadian rhythm assays using U2OS Bmal1-dLuc cells, TW68 extended the period length of the circadian rhythm. Additionally, TW68 decreased the transcriptional levels of two genes, Phosphoenolpyruvate carboxykinase 1 (PCK1) and Glucose-6-phosphatase (G6PC), which play crucial roles in glucose biosynthesis during glucagon-induced gluconeogenesis in HepG2 cells. Oral administration of TW68 in mice showed good tolerance, a good pharmacokinetic profile, and remarkable bioavailability. Finally, when administered to fasting diabetic animals from ob/ob and HFD-fed obese mice, TW68 reduced blood glucose levels by enhancing CRY stabilization and subsequently decreasing the transcriptional levels of Pck1 and G6pc. These findings collectively demonstrate the antidiabetic efficacy of TW68 in vivo, suggesting its therapeutic potential for controlling fasting glucose levels in the treatment of type 2 diabetes mellitus.

Genomic Characterization of Salmonella enterica Resistant to Cephalosporin, Quinolones, And Macrolides.

Salmonella enterica subsp. enterica (Salmonella), one of the most common causes of bacterial foodborne infections, causes salmonellosis, which is usually self-limiting. However, immunocompromised individuals and children often require antimicrobial therapy. The first line of treatment includes fluoroquinolones, to which Salmonella has emerging resistance worldwide. In fact, the WHO classified fluoroquinolone-resistant Salmonella as a high-priority pathogen. Salmonella carrying genes such as blaCTX and blaCMY can show resistance to cephalosporins which are also regularly used for treatment. This study focused on determining the antimicrobial resistance of 373 Salmonella isolates, collected from various foods, humans, and animals, as well as the environmental sludge between 2005 and 2020 in Türkiye. Phenotypic analysis of the resistance was determined by disk diffusion method. Isolates resistant to any of the following: ciprofloxacin, pefloxacin, azithromycin, and ceftriaxone were tested for the presence of quinolone, beta-lactamase, and/or macrolide resistance genes by PCR and gel electrophoresis. Five multi-drug-resistant isolates were then further whole genome sequenced and analyzed. More than 32% (n = 120) of the isolates showed resistance to fluoroquinolones by disc diffusion. A significant number of quinolone-resistant isolates are presented with mutated parC and gyrA. Furthermore, 42% (n = 106) of the isolates were resistant to azithromycin and 10% of them harbored mphA gene. On the bright side, only eight isolates showed resistance to ceftriaxone. Overall, we observed an increase in the number of isolates showing resistance to fluoroquinolones and azithromycin over the years and low resistance to ceftriaxone.

Emerging Increase in Colistin Resistance Rates in Escherichia coli and Salmonella enterica from Türkiye.

Foodborne infections caused by drug-resistant Salmonella spp. are a global health concern. Moreover, commensal Escherichia coli is considered risky due to the presence of antimicrobial resistance genes. Colistin is considered a last-resort antibiotic against Gram-negative bacterial infections. Colistin resistance can be transferred both vertically, and horizontally via conjugation between bacterial species. Plasmid-mediated resistance has been associated with mcr-1 to mcr-10 genes. In this study, we collected food samples (n = 238), and isolated E. coli (n = 36) and Salmonella (n = 16), representing recent isolates. We included previously collected Salmonella (n = 197) and E. coli (n = 56) from various sources from 2010 to 2015 in Türkiye as representing historical isolates to investigate colistin-resistance over time. In all isolates, colistin resistance was screened phenotypically by minimum inhibitory concentration (MIC), and then in resistant isolates, mcr-1 to mcr-5 genes were further screened. In addition, the antibiotic resistance of recent isolates was determined, and antibiotic resistance genes were investigated. We found that in total 20 Salmonella isolates (9.38%) and 23 of the E. coli isolates (25%) showed phenotypic colistin resistance. Interestingly, the majority of colistin-resistant isolates (N:32) had resistance levels above 128 mg/L. Furthermore 75% of commensal E. coli isolates recently isolated were resistant at least 3 antibiotics. Overall, we found that the colistin resistance has been increased from 8.12 to 25% in Salmonella isolates, and 7.14% to 52.8% in E. coli isolates over time. However, none of these resistant isolates carried mcr genes, most likely indicating emerging chromosomal colistin resistance.

Recent advancements in natural colorants and their application as coloring in food and in intelligent food packaging.

Colorants are widely employed in the food industry as an essential ingredient in many products since color is one of the most valued attributes by consumers. Furthermore, the utilization of colorants is currently being extended to the food packaging technologies. The objective of this review was to compile recent information about the main families of natural coloring compounds, and to describe their real implications in food coloring. In addition, their technological use in different food systems (namely, bakery products, beverages, meat and meat products, and dairy products) and their utilization in intelligent packaging to monitor the freshness of foodstuffs with the aim of extending food shelf life and improving food properties was discussed. The potential of using natural colorant in different food to improve their color has been demonstrated, although color stability is still a challenging task. More interestingly, the application of intelligent colorimetric indicators to exhibit color changes with variations in pH can enable real-time monitoring of food quality.

An economical and practical procedure of favipiravir synthesis for the treatment of Covid-19.

Favipiravir is a wide-spectrum antiviral generic drug that has received large attention during the recent COVID-19 pandemic. While there are synthetic strategies for favipiravir synthesis, economical procedures could contribute to industrial scale synthesis and availability. Accordingly, our efforts focused on an economic and scalable procedure for favipiravir synthesis via the 3,6-dichloropyrazine-2-carbonitrile intermediate obtained from 3-aminopyrazine-2-carboxylic acid. The process afforded favipiravir with 43% yield (from 3,6-dichloropyrazine-2-carbonitrile, by fluorination, hydroxylation, and nitrile hydrolysis reactions) and greater than 99% purity without a chromatographic purification step. Supplementary Information: The online version contains supplementary material available at 10.1007/s11696-022-02595-1.

Cytotoxic Activity and Docking Studies of 2-arenoxybenzaldehyde N-acyl Hydrazone and 1,3,4-Oxadiazole Derivatives against Various Cancer Cell Lines.

To understand whether previously synthesized novel hydrazone and oxadiazole derivatives have promising anticancer effects, docking studies and in vitro toxicity assays were performed on A-549, MDA-MB-231, and PC-3 cell lines. The antiproliferative properties of the compounds were investigated using molecular docking experiments. Each compound's best-docked poses, binding affinity, and receptor-ligand interaction were evaluated. Compounds' molecular weights, logPs, TPSAs, abilities to pass the blood-brain barrier, GI absorption qualities, and CYPP450 inhibition have been given. When the activities of these molecules were examined in vitro, for the A-549 cell line, hydrazone 1e had the minimum IC50 value of 13.39 µM. For the MDA-MB-231 cell line, oxadiazole 2l demonstrated the lowest IC50 value, with 22.73 µM. For PC-3, hydrazone 1d showed the lowest C50 value of 9.38 µM. The three most promising compounds were determined as compounds 1e, 1d, and 2a based on their minimum IC50 values, and an additional scratch assay was performed for A-549 and MDA-MB-231 cells, which have high migration capacity, for the three most potent molecules; it was determined that these molecules did not show a significant antimetastatic effect.

Discovery of a small molecule that selectively destabilizes Cryptochrome 1 and enhances life span in p53 knockout mice.

Cryptochromes are negative transcriptional regulators of the circadian clock in mammals. It is not clear how reducing the level of endogenous CRY1 in mammals will affect circadian rhythm and the relation of such a decrease with apoptosis. Here, we discovered a molecule (M47) that destabilizes Cryptochrome 1 (CRY1) both in vitro and in vivo. The M47 selectively enhanced the degradation rate of CRY1 by increasing its ubiquitination and resulted in increasing the circadian period length of U2OS Bmal1-dLuc cells. In addition, subcellular fractionation studies from mice liver indicated that M47 increased degradation of the CRY1 in the nucleus. Furthermore, M47-mediated CRY1 reduction enhanced oxaliplatin-induced apoptosis in Ras-transformed p53 null fibroblast cells. Systemic repetitive administration of M47 increased the median lifespan of p53-/- mice by ~25%. Collectively our data suggest that M47 is a promising molecule to treat forms of cancer depending on the p53 mutation.

Mechanistic insight into impact of phosphorylation on the enzymatic steps of farnesyltransferase.

Farnesyltransferase (FTase) is a heterodimeric enzyme, which catalyzes covalent attachment of the farnesyl group to target proteins, thus coordinating their trafficking in the cell. FTase has been demonstrated to be highly expressed in cancer and neurological diseases; hence considered as a hot target for therapeutic purposes. However, due to the nonspecific inhibition, there has been only one inhibitor that could be translated into the clinic. Importantly, it has been shown that phosphorylation of the α-subunit of FTase increases the activity of the enzyme in certain diseases. As such, understanding the impact of phosphorylation on dynamics of FTase provides a basis for targeting a specific state of the enzyme that emerges under pathological conditions. To this end, we performed 18 µs molecular dynamics (MD) simulations using complexes of (non)-phosphorylated FTase that are representatives of the farnesylation reaction. We demonstrated that phosphorylation modulated the catalytic site by rearranging interactions between farnesyl pyrophosphate (FPP)/peptide substrate, catalytic Zn2+ ion/coordinating residues and hot-spot residues at the interface of the subunits, all of which led to the stabilization of the substrate and facilitation of the release of the product, thus collectively expediting the reaction rate. Importantly, we also identified a likely allosteric pocket on the phosphorylated FTase, which might be used for specific targeting of the enzyme. To the best of our knowledge, this is the first study that systematically examines the impact of phosphorylation on the enzymatic reaction steps, hence opens up new avenues for drug discovery studies that focus on targeting phosphorylated FTase.

Potential of Novel Methyl Jasmonate Analogs as Anticancer Agents to Metabolically Target HK-2 Activity in Glioblastoma Cells.

Change in the energy metabolism of cancer cells, which display significant differences compared to normal cells, is a rising phenomenon in developing new therapeutic approaches against cancers. One of the metabolic enzymes, hexokinase-II (HK-II) is involved in glycolysis, and inhibiting the HK-II activity may be a potential metabolic target for cancer therapy as most of the drugs in clinical use act on DNA damage. Methyl jasmonate (MJ) is one of the compounds blocking HK-II activity in cancer cells. In a previous study, we showed that the novel MJ analogs inhibit HK-II activity through VDAC detachment from the mitochondria. In this study, to evaluate the potential of targeting HK-2 activity, through patient cohort analysis, we first determined HK-2 expression levels and prognostic significance in highly lethal glioblastoma (GBM) brain tumor. We then examined the in vitro therapeutic effects of the novel analogs in the GBM cells. Here, we report that, among all, compound-10 (C-10) showed significant in vitro therapeutic efficacy as compared to MJ which is in use for preclinical and clinical studies. Afterward, we analyzed cell death triggered by C-10 in two different GBM cell lines. We found that C-10 treatment increased the apoptotic/necrotic cells and autophagy in GBM cells. The newly developed analog, C-10, was found to be lethal against GBM by the activation of cell death authorities, mostly in a necrotic and autophagic fashion at the early stages of the treatment. Considering that possibly decreased intracellular ATP levels by C-10 mediated inhibition of HK-2 activity and disabled VDAC interaction, a more detailed analysis of HK-2 inhibition-mediated cell death can provide a deep understanding of the mechanism of action on the oncosis/necroptosis axis. These findings provide an option to design clinically relevant and effective novel HK-II inhibitors and suggest novel MJ analogs to further study them as potential anticancer agents against GBM.

The Effects of Increased Glucose Level and Glycolysis on SARS CoV-2 Infection.

COVID-19 has entered our lives as an infection with high mortality rates. Although the vaccination process has provided benefits, the death toll remains frightening worldwide. Therefore, drugs and combined therapies that can be used against COVID-19 infection are still being investigated. Most of these antiviral medications are investigational drug candidates that are still in clinical trials. In this context, holistic and different approaches for the treatment of COVID-19, including prophylactic use of natural medicines, are under investigation and may offer potential treatment options due to the fact that this is still an unmet medical need of the world. Thus, inhibiting the increased glycolysis in COVID-19 infection with glycolysis inhibitors may be beneficial for patient survival. This short review highlights the potential benefits of glycolysis inhibition as well as controlling the elevated glucose levels in patients with COVID-19.

Design and synthesis of novel caffeic acid phenethyl ester (CAPE) derivatives and their biological activity studies in glioblastoma multiforme (GBM) cancer cell lines.

Glioblastoma Multiforme (GBM) is the most aggressive brain tumor and classified as one of the deadliest cancers. The current treatment plans for GBM remains to be ineffective because of its rapid progress and inability of the drugs used to cross the blood-brain barrier (BBB). Thus, developing more effective and potent medicines for GBM are needed. There have been several reports demonstrating that CAPE presents reasonably good anti-cancer activity in certain cancer cell lines and can penetrate the blood-brain barrier. Accordingly, in this study we synthesized several novel CAPE analogs with the addition of more druggable handles and solubilizing entities and subsequently evaluated their in vitro therapeutic efficacies in GBM cell lines (T98G and LN229). The most potent compound was then examined extensively and results showed that the 50 µM novel CAPE analog (compound 10) significantly decreases the viability of both T98G and LN229 GBM cells as compared to CAPE itself. Moreover, the compound 10 was not cytotoxic to healthy human cells (fibroblast-like mesenchymal stem cells) at the same concentration. Apoptotic (32.8%, and 44.6%) cell populations were detected in the compound 10 treated groups for LN229 and T98G, respectively. As an indication of apotosis, significantly increased PARP cleavage was detected in compound 10 versus CAPE treated LN229. In addition, we conducted molecular docking and molecular dynamics (MD) simulations studies on certain targets playing roles on GBM disease pathway such as NF-κB, EGFR, TNF-α, ERK2, PAPR1, hCA IX and hCA XII. Our findings demonstrated that designed CAPE analogs have anti-cancer activity on GBM cells and in silico studies also demonstrate the inhibitory ability of suggested compounds via interactions with critical residues in binding pockets of studied targets. Here, we suggest the novel CAPE analog to study further against GBM. Therefore, identification of the compound related molecular signature may provide more to understand the mechanism of action.

The neutralization effect of montelukast on SARS-CoV-2 is shown by multiscale in silico simulations and combined in vitro studies.

Small molecule inhibitors have previously been investigated in different studies as possible therapeutics in the treatment of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). In the current drug repurposing study, we identified the leukotriene (D4) receptor antagonist montelukast as a novel agent that simultaneously targets two important drug targets of SARS-CoV-2. We initially demonstrated the dual inhibition profile of montelukast through multiscale molecular modeling studies. Next, we characterized its effect on both targets by different in vitro experiments including the enzyme (main protease) inhibition-based assay, surface plasmon resonance (SPR) spectroscopy, pseudovirus neutralization on HEK293T/hACE2+TMPRSS2, and virus neutralization assay using xCELLigence MP real-time cell analyzer. Our integrated in silico and in vitro results confirmed the dual potential effect of montelukast both on the main protease enzyme inhibition and virus entry into the host cell (spike/ACE2). The virus neutralization assay results showed that SARS-CoV-2 virus activity was delayed with montelukast for 20 h on the infected cells. The rapid use of new small molecules in the pandemic is very important today. Montelukast, whose pharmacokinetic and pharmacodynamic properties are very well characterized and has been widely used in the treatment of asthma since 1998, should urgently be completed in clinical phase studies and, if its effect is proved in clinical phase studies, it should be used against coronavirus disease 2019 (COVID-19).

Instant determination of the artemisinin from various Artemisia annua L. extracts by LC-ESI-MS/MS and their in-silico modelling and in vitro antiviral activity studies against SARS-CoV-2.

INTRODUCTION: Numerous efforts in natural product drug development are reported for the treatment of Coronavirus. Based on the literature, among these natural plants Artemisia annua L. shows some promise for the treatment of SARS-CoV-2. OBJECTIVE: The main objective of our study was to determine artemisinin content by liquid chromatography electrospray ionisation tandem mass spectrometry (LC-ESI-MS/MS), to investigate the in vitro biological activity of artemisinin from the A. annua plants grown in Turkey with various extracted methods, to elaborate in silico activity against SARS-CoV-2 using molecular modelling. METHODOLOGY: Twenty-one different extractions were applied. Direct and sequential extractions studies were compared with ultrasonic assisted maceration, Soxhlet, and ultra-rapid determined artemisinin active molecules by LC-ESI-MS/MS methods. The inhibition of spike protein and main protease (3CL) enzyme activity of SARS-CoV-2 virus was assessed by time resolved fluorescence energy transfer (TR-FRET) assay. RESULTS: Artemisinin content in the range 0.062-0.066%. Artemisinin showed significant inhibition of 3CL protease activity but not Spike/ACE-2 binding. The 50% effective concentration (EC50 ) of artemisinin against SARS-CoV-2 Spike pseudovirus was found greater than 50 µM (EC45 ) in HEK293T cell line whereas the cell viability was 94% of the control (P < 0.01). The immunosuppressive effects of artemisinin on TNF-α production on both pseudovirus and lipopolysaccharide (LPS)-induced THP-1 cells were found significant in a dose dependent manner. CONCLUSION: Further studies of these extracts for COVID-19 treatment will shed light to seek alternative treatment options. Moreover, these natural extracts can be used as an additional treatment option with medicines, as well as prophylactic use can be very beneficial for patients.

Hydroxychloroquine Attenuates Acute Inflammation (LPS)-Induced Apoptosis via Inhibiting TRPV1 Channel/ROS Signaling Pathways in Human Monocytes.

Acute inflammation (INF) and apoptosis are induced in monocytes by the generation of several factors, including the products of cytosolic oxygen free radicals (cROS) and the excessive influx of Ca2+ via the stimulation of TRPV1. These are main factors in the etiology of monocyte activation-induced inflammatory and neurodegenerative diseases. Importantly, the protective action of hydroxychloroquine (HCQ) treatment via the inhibition of TRPV1 on the levels of inflammatory factors, cROS, and apoptosis in acute INF (lipopolysaccharide, LPS)-exposed neuronal cells was recently reported. However, the relationships between acute INF via TRPV1 activation and HCQ in monocytes have not been fully clarified yet. The cell membrane of U937 human monocytes contains natural TRPV1. In the study plan, we used U937 cells in four main groups, namely control, HCQ (60 µM for 48 h), INF (1 µg/mL LPS for 16 h), and HCQ + INF. The current data indicate that LPS-induced acute INF caused the upregulation of excessive cytosolic Ca2+ accumulation via the stimulation of TRPV1 in the cells. The treatment of INF additionally upregulated the levels of apoptosis and cytokines (IL6, IL1ß, and TNFα), due to upregulated cROS and lipid peroxidation levels as well as upregulated generation of caspase -3 (CAS3) and -9 (CAS9) but a decrease in glutathione and glutathione peroxidase. The expression levels of TRPV1, Bax, CAS3, and CAS9 were also upregulated by the treatment of LPS. However, treatment with HCQ and TRPV1 blocker (capsazepine) modulated the levels of cytokines, caspases, cROS, Ca2+ influx, and apoptosis through the modulation of TRPV1 in the U937 that were stimulated with LPS. In summary, the present data suggest TRPV1 activation through the acute INF (LPS)-induced inflammatory, oxidant, and apoptotic adverse actions in monocyte cells, whereas HCQ prevented adverse actions via the modulation of TRPV1. The results may be significant in the modulation of monocyte activation-caused inflammatory and neurodegenerative diseases.

Diagnostic and early prognostic value of serum CRP and LDH levels in patients with possible COVID-19 at the first admission.

INTRODUCTION: COVID-19 is the infection caused by the new coronavirus. Specific treatment for COVID-19 has not been established, yet. It is important to determine the disease severity of the patients at the first admission. Therefore, the exploration of biomarkers is deemed necessary. We aimed to assess the diagnostic and early prognostic value of CRP and LDH levels in possible COVID-19 patients presenting with a severe clinical picture. METHODOLOGY: We evaluated the correlations of relevant routine laboratory test results with disease severity in COVID-19 patients admitted to our infectious diseases clinic. Patients were divided into severe and non-severe disease groups based on clinical findings, oxygen saturation levels in the arterial blood, biochemical test results, and radiological findings. Differences in the findings between the two disease severity groups were examined to determine potential biomarkers. RESULTS: Median age and the CRP and LDH levels in the severe disease group were statistically significantly higher compared to the nonsevere group (p < 0.0001). No other parameters statistically significant differences have been observed between the two groups (P > 0.05). CONCLUSIONS: CRP and LDH levels were positively correlated with lung lesions in early-stage COVID-19, potentially reflecting disease severity. Because LDH and CRP levels can potentially reflect the pulmonary function, they can be potential predictors of COVID-19- related respiratory failure. For avoiding poor prognosis; LDH and CRP should be considered as potential predictors for identifying the need for thoracic CT scans, close monitoring of pulmonary function, and aggressive supportive therapy early in the course of COVID-19.

Diagnostic values of HNP 1-3 and procalcitonin levels in synovial fluid aspirates in the differential diagnosis between septic arthritis and noninfectious arthritis.

INTRODUCTION: Although early diagnosis of septic arthritis may reduce mortality rates, and limit unnecessary surgical interventions, clinical parameters alone are not adequate for making the diagnosis of septic arthritis. Therefore, relevant laboratory parameters are used to enhance diagnostic sensitivity. The aim of our study was to assist in making the diagnosis of septic arthritis, and prevent delays in the diagnosis. For this purpose; we aimed to determine the diagnostic values of human neutrophil peptides 1-3 (HNP 1-3) and procalcitonin (PCT) in synovial fluids of patients with arthritis. By comparing the HNP 1-3 and procalcitonin levels, as well as CRP, in synovial fluid aspirates, we evaluated the significance of these data in the differential diagnosis of septic arthritis from noninfectious arthritis. METHODS: A total of 67 adults consisting of 37 septic arthritis and 30 noninfectious arthritis patients were included in our study. As bioindicators; levels of HNP 1-3, PCT, synovial and serum CRP levels were found to have significant ROC areas in discriminating septic arthritis patients from noninfectious arthritis patients. RESULTS: As a result, synovial fluid HNP 1-3 levels were significantly higher in septic arthritis patients compared to noninfectious arthritis patients (p < 0.001). The sensitivity, specificity, and accuracy of HNP 1-3 levels in the diagnosis of septic and noninfectious arthritis were found as 86%, 87%, and 87%, respectively (AUC of the ROC curve = 0.828). CONCLUSIONS: It was decided that the level of HNP 1-3 in the synovial fluid can be used as an alternative indicator in the diagnosis of septic arthritis.

Interferon Gamma-Mediated Oxidative Stress Induces Apoptosis, Neuroinflammation, Zinc Ion Influx, and TRPM2 Channel Activation in Neuronal Cell Line: Modulator Role of Curcumin.

Host defenses in the brain are modulated by the activation of several factors such as oxygen free radical species (ROS), Ca2+ influx, and TRPM2 activation, and they are well-known adverse factors in neurotoxicity and neurodegenerative diseases. Importantly, recent data indicated a protective action of curcumin (CRC) via inhibition of TRPM2 on the inflammation factors, ROS, and apoptosis in hypoxia-induced SH-SY5Y neuronal cells. However, the relationship between interferon gamma (IFNg) exposure and TRPM2 activation in the SH-SY5Y cells are not fully identified. The SH-SY5Y cells as a neuronal cell line model were used in several neuroinflammation studies. Hence, we used the SH-SY5Y cells in the current study, and they were divided into four main groups as control, CRC, IFNg, and IFNg+CRC. The data presented here indicate that IFNg induced excessive Ca2+ influx via activation of TRPM2. The IFNg treatment further increased cell death, cell debris amount, apoptosis, and cytokine generations (IL-1ß, IL-6, and TNF-α) which were due to increased cytosolic and mitochondrial ROS generations as well as increased activations of caspase-3 and caspase-9. The expression levels of TRPM2, PARP-1, Bax, caspase-3, and caspase-9 were increased in the cells by the IFNg treatment. However, CRC treatment reduced the increase of expression levels, cytokine generations, caspase activations, ROS release, Ca2+ influx, cell death, and apoptosis levels via inhibition of TRPM2 in the SH-SY5Y cells that were treated with IFNg. Moreover, the treatment of TRPM2 blockers (ACA and 2-APB) potentiated the modulator effects of CRC. In conclusion, these results suggest that neuroinflammation via IFNg lead to the TRPM2 activation in the SH-SY5Y cells, whereas CRC prevents IFNg-mediated TRPM2 activation, cell death, and cytokine generations.

Identification and Characterization of 33 Bacillus cereus sensu lato Isolates from Agricultural Fields from Eleven Widely Distributed Countries by Whole Genome Sequencing.

The phylogeny, identification, and characterization of 33 B. cereus sensu lato isolates originating from 17 agricultural soils from 11 countries were analyzed on the basis of whole genome sequencing. Phylogenetic analyses revealed all isolates are divided into six groups, which follows the generally accepted phylogenetic division of B. cereus sensu lato isolates. Four different identification methods resulted in a variation in the identity of the isolates, as none of the isolates were identified as the same species by all four methods-only the recent identification method proposed directly reflected the phylogeny of the isolates. This points to the importance of describing the basis and method used for the identification. The presence and percent identity of the protein product of 19 genes potentially involved in pathogenicity divided the 33 isolates into groups corresponding to phylogenetic division of the isolates. This suggests that different pathotypes exist and that it is possible to differentiate between them by comparing the percent identity of proteins potentially involved in pathogenicity. This also reveals that a basic link between phylogeny and pathogenicity is likely to exist. The geographical distribution of the isolates is not random: they are distributed in relation to their division into the six phylogenetic groups, which again relates to different ecotypes with different temperature growth ranges. This means that we find it easier to analyze and understand the results obtained from the 33 B. cereus sensu lato isolates in a phylogenetic, patho-type and ecotype-oriented context, than in a context based on uncertain identification at the species level.

Prevalence of Rotavirus-Associated Acute Gastroenteritis Cases in Early Childhood in Turkey: Meta-Analysis.

BACKGROUND: Rotavirus is globally the most common viral pathogen in childhood gastroenteritis. This study aimed to estimate the number of Turkish children suffering from early-childhood gastroenteritis by rotavirus by performing a meta-analysis. METHODS: Meta-analysis following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was performed. Following the guidelines, primary studies were found reporting the prevalence of rotavirus gastroenteritis in Turkey. We performed a computerized search of published studies in national and international databases from 1990 to 2018. We selected 38 out of 721 studies for our study. Meta-analysis was carried out using R statistical software. The Cochrane Q statistic was calculated to assess the heterogeneity of the study results. Heterogeneity among studies was evaluated using the I2 statistic. Effect-size estimate was reported with 95% confidence interval. RESULTS: On the basis of 38 selected articles, 80,113 children up to five years of age were diagnosed with symptoms of acute gastroenteritis, of whom the stool samples of 13,651 children were positive for rotavirus. The pooled prevalence of rotavirus was 19% in children younger than five years of age with acute gastroenteritis. In terms of seasonal prevalence, the highest prevalence rate was found in winter. CONCLUSION: This study supports the major prevalence of early-childhood gastroenteritis by rotavirus among Turkish children. Therefore, the decision to adopt immunization programs to prevent rotavirus infection might be helpful in Turkey.