Euryops arabicus (Asteraceae) is grown in Arab Peninsula. Its aerial parts possess ethnomedicinal applications against several inflammatory conditions.

Our previous study reported that persistently infected (PI) cattle of bovine viral diarrhea virus (BVDV) have co-infected with BVDV/END- and /END+ that promote and inhibit host's type-I interferon (IFN) production, respectively. However, the relationship between co-infection of immunologically distinct BVDVs and persistent infection as well as the biological significance of END- viruses remains unknown. Experiments using cultured cells revealed that END+ virus, which is unable to propagate in situations where the host's immune response is induced by IFN-α addition, is able to propagate under those conditions when co-infecting with END- virus. These results indicate that BVDV/END- can coexist with BVDV/END+ and that co-infection with END- viruses supports the propagation of END+ viruses. Our in vitro experiments strongly suggest that co-infection with END- virus is involved in the maintenance of persistent infection of BVDV.

Tumor-associated macrophages (TAMs) are abundant in many cancers, and predominately display an immunosuppressive M2-like function that fosters tumor progression and promotes malignant metastasis. Current TAMs repolarization strategies mainly focused on harnessing the direct cancer cell killing property of M1-like macrophages repolarized from TAMs. However, the latent role of M1-like macrophages as professional antigen-presenting cells (APCs) also needs to be explored. Here, iron chelated melanin-like nanoparticles (Fe@PDA-PEG) were developed for M2-to-M1 TAMs repolarization and photothermal therapy (PTT) induced tumor-associated antigens (TAAs) releasing, which would exploit the potential of M1-like macrophages acquired as professional APCs for TAAs presentation. The results showed that M1 macrophages repolarized from TAMs by Fe@PDA-PEG could capture, process and present TAAs released by PTT through the major histocompatibility complex class II (MHC II) pathway, recruiting T-helper cells and effector T cells in tumor site, which leads to the controlled tumor growth and limited malignant metastasis.

Chronic rhinosinusitis (CRS) is defined as a chronic inflammation of the nose and paranasal sinus mucosa associated with relapsing infections-particularly with S. aureus. Long-term treatments with protein synthesis inhibitor antibiotics have been proposed to reduce inflammation in the context chronic severe inflammatory airway pathologies, including CRS. This study assessed the effect of subinhibitory clindamycin and azithromycin on S. aureus exoprotein induced inflammation, toxicity and invasiveness.

A hollow-type spherical bacterial cellulose (HSBC) gel prepared using conventional methods cannot load particles larger than the pore size of the cellulose nanofiber network of bacterial cellulose (BC) gelatinous membranes. In this study, we prepared a HSBC gel encapsulating target substances larger than the pore size of the BC gelatinous membranes using two encapsulating methods. The first method involved producing the BC gelatinous membrane on the surface of the core that was a spherical alginate gel with a diameter of 2 to 3 mm containing the target substances. With this method, the BC gelatinous membrane was biosynthesized using Gluconacetobacter xylinus at the interface between the cell suspension attached onto the alginate gel and the silicone oil. The second method involved producing the BC gel membrane on the interface between the silicone oil and cell suspension, as well as the spherical alginate gel with a diameter of about 1 mm containing target substances. After the BC gelatinous membrane was biosynthesized, an alginate gel was dissolved in a phosphate buffer to prepare an HSBC gel with the target substances. These encapsulated substances could neither pass through the BC gelatinous membrane of the HSBC gel nor leak from the interior space of the HSBC gel. These results suggest that the HSBC gel had a molecular sieving function. The HSBC gel walls prepared using these methods were observed to be uniform and would be useful for encapsulating bioactive molecules, such as immobilized enzymes in HSBC gel, which is expected to be used as a drug carrier.

Isorhamnetin is an O-methylated flavonol that is predominantly found in the fruits and leaves of various plants, which have been used for traditional herbal remedies. Although several previous studies have reported that this flavonol has diverse health-promoting effects, evidence is still lacking for the underlying molecular mechanism of its anti-cancer efficacy. In this study, we examined the anti-proliferative effect of isorhamnetin on human bladder cancer cells and found that isorhamnetin triggered the gap 2/ mitosis (G2/M) phase cell arrest and apoptosis. Our data showed that isorhamnetin decreased the expression of Wee1 and cyclin B1, but increased the expression of cyclin-dependent kinase (Cdk) inhibitor p21WAF1/CIP1, and increased p21 was bound to Cdk1. In addition, isorhamnetin-induced apoptosis was associated with the increased expression of the Fas/Fas ligand, reduced ratio of B-cell lymphoma 2 (Bcl-2)/Bcl-2 associated X protein (Bax) expression, cytosolic release of cytochrome c, and activation of caspases. Moreover, isorhamnetin inactivated the adenosine 5'-monophosphate-activated protein kinase (AMPK) signaling pathway by diminishing the adenosine triphosphate (ATP) production due to impaired mitochondrial function. Furthermore, isorhamnetin stimulated production of intracellular reactive oxygen species (ROS); however, the interruption of ROS generation using a ROS scavenger led to an escape from isorhamnetin-mediated G2/M arrest and apoptosis. Collectively, this is the first report to show that isorhamnetin inhibited the proliferation of human bladder cancer cells by ROS-dependent arrest of the cell cycle at the G2/M phase and induction of apoptosis. Therefore, our results provide an important basis for the interpretation of the anti-cancer mechanism of isorhamnetin in bladder cancer cells and support the rationale for the need to evaluate more precise molecular mechanisms and in vivo anti-cancer properties.

Celebrity endorsement used to promote energy-dense and nutrient-poor (EDNP) food and beverage products may contribute to poor dietary habits. This study examined celebrity endorsement of branded food and beverage products and marketing campaigns in the United States (US) from 1990 to 2017. Celebrity endorsement data were collected from peer-reviewed and grey literature. Interactive data visualizations were created for the endorsement relationships between celebrities, companies and products whose nutritional profiles were compared with the US Department of Agriculture's (USDA's) Smart Snacks Standards. Logistic regression was used to explore associations between celebrities' demographic profiles and the nutritional profiles of products. Results showed 542 celebrities were associated with 732 endorsements representing 120 brands of 59 companies across 10 food and beverage categories. Two thirds (67.2%; n = 80) of the brands represented EDNP products that did not align with the USDA's Smart Snacks Standards. Logistic regression analysis indicated that Millennial (p = 0.008) and male celebrities (p = 0.041) were more likely to endorse EDNP products than Generation Z teen and female celebrities, respectively. No statistical significance was observed for celebrities of other demographic profiles. This study may inform future policies and actions of the US government, industry, researchers and consumer advocacy organizations to use celebrity endorsement to promote healthy food environments for Americans.

Several biotic and abiotic factors can influence the amount of polyphenols in grape tissues. During vinification, the temperature, presence of grape seeds and peel, and use of enzymes, can influence the extraction of polyphenols. However, little information is available on the effects of yeast strains used in the polyphenolic composition of wine. With this aim, two selected Saccharomyces cerevisiae strains, ITEM 14093 and ITEM 14077 were used to produce wine from two Italian grape cultivars, Primitivo and Negroamaro. At the end of the alcoholic fermentation, the content of total polyphenols and of particular classes of polyphenols (stilbenes, phenolic acids, flavonols, and flavanols) and the antioxidant activity were evaluated and compared in the obtained wines. We also examined the effects of red wine extracts in a culture model of vascular inflammation. The results obtained comparing wine extracts obtained by utilizing commercial or autochthonous yeast showed that wines obtained with selected yeast significantly inhibited vascular inflammation. The results are positively directed towards the healthy properties of wine drinking.

: The preservation of muscle mass and muscle function after weight loss therapy is currently a considerable challenge in the fight against obesity. Muscle mass secretes proteins called myokines that have relevant functions in the regulation of metabolism and health. This study was aimed to evaluate whether a very low-calorie ketogenic (VLCK) diet may modulate myokine levels, in addition to changes in body composition, compared to a standard, balanced low-calorie (LC) diet or bariatric surgery in patients with obesity. Body composition, ketosis, insulin sensitivity and myokines were evaluated in 79 patients with overweight/obesity after a therapy to lose weight with a VLCK diet, a LC diet or bariatric surgery. The follow-up was 6 months. The weight loss therapies induced changes in myokine levels in association with changes in body composition and biochemical parameters. The effects on circulating myokine levels compared to those at baseline were stronger after the VLCK diet than LC diet or bariatric surgery. Differences reached statistical significance for IL-8, MMP2 and irisin. In conclusion, nutritional interventions or bariatric surgery to lose weight induces changes in circulating myokine levels, being this effect potentially most notable after following a VLCK diet.

For cancer diagnosis, many DNA methylation markers have been identified. However, few studies have tried to identify DNA methylation markers to diagnose diverse cancer types simultaneously, i.e., pan-cancers. In this study, we tried to identify DNA methylation markers to differentiate cancer samples from the respective normal samples in pan-cancers. We collected whole genome methylation data of 27 cancer types containing 10,140 cancer samples and 3386 normal samples, and divided all samples into five data sets, including one training data set, one validation data set and three test data sets. We applied machine learning to identify DNA methylation markers, and specifically, we constructed diagnostic prediction models by deep learning. We identified two categories of markers: 12 CpG markers and 13 promoter markers. Three of 12 CpG markers and four of 13 promoter markers locate at cancer-related genes. With the CpG markers, our model achieved an average sensitivity and specificity on test data sets as 92.8% and 90.1%, respectively. For promoter markers, the average sensitivity and specificity on test data sets were 89.8% and 81.1%, respectively. Furthermore, in cell-free DNA methylation data of 163 prostate cancer samples, the CpG markers achieved the sensitivity as 100%, and the promoter markers achieved 92%. For both marker types, the specificity of normal whole blood was 100%. To conclude, we identified methylation markers to diagnose pan-cancers, which might be applied to liquid biopsy of cancers.

Rapid urban expansion and increased human activities have led to the progressive deterioration of many marine ecosystems. The diverse microbial communities that inhabit these ecosystems are believed to influence large-scale geochemical processes and, as such, analyzing their composition and functional metabolism can be a means to assessing an ecosystem's resilience to physical and chemical perturbations, or at the very least provide baseline information and insight into future research needs. Here we show the utilization of organic and inorganic contaminant screening coupled with metabolomics and bacterial 16S rRNA gene sequencing to assess the microbial community structure of marine sediments and their functional metabolic output. The sediments collected from Moreton Bay (Queensland, Australia) contained low levels of organic and inorganic contaminants, typically below guideline levels. The sequencing dataset suggest that sulfur and nitrite reduction, dehalogenation, ammonia oxidation, and xylan degradation were the major metabolic functions. The community metabolites suggest a level of functional homogeneity down the 40-cm core depth sampled, with sediment habitat identified as a significant driver for metabolic differences. The communities present in river and sandy channel samples were found to be the most active, with the river habitats likely to be dominated by photoheterotrophs that utilized carbohydrates, fatty acids and alcohols as well as reduce nitrates to release atmospheric nitrogen and oxidize sulfur. Bioturbated mud habitats showed overlapping faunal activity between riverine and sandy ecosystems. Nitrogen-fixing bacteria and lignin-degrading bacteria were most abundant in the sandy channel and bioturbated mud, respectively. The use of omics-based approaches provide greater insight into the functional metabolism of these impacted habitats, extending beyond discrete monitoring to encompassing whole community profiling that represents true phenotypical outputs. Ongoing omics-based monitoring that focuses on more targeted pathway analyses is recommended in order to quantify the flux changes within these systems and establish variations from these baseline measurements.

Multiple external root resorption (MERR) has been reported in systemic sclerosis (SSc) patients in Japan and Spain. To establish whether MERR is a new manifestation, we investigated the prevalence of MERR and systemic and oral manifestations to be associated with MERR in patients with SSc.

Dravet syndrome is a type of severe childhood epilepsy that responds poorly to current anti-epileptic drugs. In recent years, zebrafish disease models with Scn1Lab sodium channel deficiency have been generated to seek novel anti-epileptic drug candidates, some of which are currently undergoing clinical trials. However, the spectrum of neuronal deficits observed following Scn1Lab depletion in zebrafish larvae has not yet been fully explored. To fill this gap and gain a better understanding of the mechanisms underlying neuron hyperexcitation in Scn1Lab-depleted larvae, we analyzed neuron activity in vivo using combined local field potential recording and transient calcium uptake imaging, studied the distribution of excitatory and inhibitory synapses and neurons as well as investigated neuron apoptosis. We found that Scn1Lab-depleted larvae displayed recurrent epileptiform seizure events, associating massive synchronous calcium uptakes and ictal-like local field potential bursts. Scn1Lab-depletion also caused a dramatic shift in the neuronal and synaptic balance toward excitation and increased neuronal death. Our results thus provide in vivo evidence suggesting that Scn1Lab loss of function causes neuron hyperexcitation as the result of disturbed synaptic balance and increased neuronal apoptosis.

Glycoconjugates are the most diverse biomolecules of life. Mostly located at the cell surface, they translate into cell-specific "barcodes" and offer a vast repertoire of functions, including support of cellular physiology, lifestyle, and pathogenicity. Functions can be fine-tuned by non-carbohydrate modifications on the constituting monosaccharides. Among these modifications is pyruvylation, which is present either in enol or ketal form. The most commonly best-understood example of pyruvylation is enol-pyruvylation of N-acetylglucosamine, which occurs at an early stage in the biosynthesis of the bacterial cell wall component peptidoglycan. Ketal-pyruvylation, in contrast, is present in diverse classes of glycoconjugates, from bacteria to algae to yeast-but not in humans. Mild purification strategies preventing the loss of the acid-labile ketal-pyruvyl group have led to a collection of elucidated pyruvylated glycan structures. However, knowledge of involved pyruvyltransferases creating a ring structure on various monosaccharides is scarce, mainly due to the lack of knowledge of fingerprint motifs of these enzymes and the unavailability of genome sequences of the organisms undergoing pyruvylation. This review compiles the current information on the widespread but under-investigated ketal-pyruvylation of monosaccharides, starting with different classes of pyruvylated glycoconjugates and associated functions, leading to pyruvyltransferases, their specificity and sequence space, and insight into pyruvate analytics.

MicroRNA (miRNA) is a small non-coding RNA that functions in the epigenetics control of gene expression, which can be used as a useful biomarker for diseases. Anti-NMDA receptor (anti-NMDAR) encephalitis is an acute autoimmune disorder. Some patients have been found to have tumors, specifically teratomas. This disease occurs more often in females than in males. Most of them have a significant recovery after tumor resection, which shows that the tumor may induce anti-NMDAR encephalitis. In this study, I review microRNA (miRNA) biomarkers that are associated with anti-NMDAR encephalitis and related tumors, respectively. To the best of my knowledge, there has not been any research in the literature investigating the relationship between anti-NMDAR encephalitis and tumors through their miRNA biomarkers. I adopt a phylogenetic analysis to plot the phylogenetic trees of their miRNA biomarkers. From the analyzed results, it may be concluded that (i) there is a relationship between these tumors and anti-NMDAR encephalitis, and (ii) this disease occurs more often in females than in males. This sheds light on this issue through miRNA intervention.

Macromolecular proton fraction (MPF) has been established as a quantitative clinically-targeted MRI myelin biomarker based on recent demyelination studies. This study aimed to assess the capability of MPF to quantify remyelination using the murine cuprizone-induced reversible demyelination model. MPF was measured in vivo using the fast single-point method in three animal groups (control, cuprizone-induced demyelination, and remyelination after cuprizone withdrawal) and compared to quantitative immunohistochemistry for myelin basic protein (MBP), myelinating oligodendrocytes (CNP-positive cells), and oligodendrocyte precursor cells (OPC, NG2-positive cells) in the corpus callosum, caudate putamen, hippocampus, and cortex. In the demyelination group, MPF, MBP-stained area, and oligodendrocyte count were significantly reduced, while OPC count was significantly increased as compared to both control and remyelination groups in all anatomic structures (p < 0.05). All variables were similar in the control and remyelination groups. MPF and MBP-stained area strongly correlated in each anatomic structure (Pearson's correlation coefficients, r = 0.80-0.90, p < 0.001). MPF and MBP correlated positively with oligodendrocyte count (r = 0.70-0.84, p < 0.01 for MPF; r = 0.81-0.92, p < 0.001 for MBP) and negatively with OPC count (r = -0.69--0.77, p < 0.01 for MPF; r = -0.72--0.89, p < 0.01 for MBP). This study provides immunohistological validation of fast MPF mapping as a non-invasive tool for quantitative assessment of de- and remyelination in white and gray matter and indicates the feasibility of using MPF as a surrogate marker of reparative processes in demyelinating diseases.

Carboxymethylcellulose (CMC) is a well-known pharmaceutical polymer, recently gaining attention in the field of nanomedicine, especially as a polyelectrolyte agent for the formation of complexes with oppositely charged macromolecules. Here, we report on the application of pH-sensitive pharmaceutical grade CMC-based nanoparticles (NP) for white blood cells (WBC) PET imaging. In this context and as an alternative to 99mTc-HMPAO SPECT labeling, the use of 68Ga3+ as PET radionuclide was investigated since, at early time points, it could provide the greater spatial resolution and patient convenience of PET tomography over SPECT clinical practices. Two operator-friendly kit-type formulations were compared, with the intention of radiolabeling within a short time (10 min), under mild conditions (physiological pH, room temperature) and in agreement with the actual clinically applied guidelines. NP were labeled by directly using 68Ga3+ eluted in HCL 0.05 N, from hospital suited 68Ge/68Ga generator and in absence of chelator. The first kit type approach involved the application of 68Ga3+ as an ionotropic gelation agent for in-situ forming NP. The second kit type approach concerned the re-hydration of a proper freeze-dried injectable NP powder. pH-sensitive NP with 250 nm average diameter and 80% labeling efficacy were obtained. The NP dispersant medium, including a cryoprotective agent, was modulated in order to optimize the Zeta potential value (-18 mV), minimize the NP interaction with serum proteins and guarantee a physiological environment for WBC during NP incubation. Time-dependent WBC radiolabeling was correlated to NP uptake by using both confocal and FT-IR microscopies. The ready to use lyophilized NP formulation approach appears promising as a straightforward 68Ga-WBC labeling tool for PET imaging applications.

This study investigated the effects and mechanisms of 1,2-bis[(3-methoxyphenyl)methyl]ethane-1,2-dicarboxylic acid (S4), a sesamin derivative, on anti-inflammation and antiphotoaging in vitro and in vivo. Human skin fibroblasts were treated with S4 and did not show cytotoxicity under concentrations of 5-50 µM. In addition, S4 also reduced ultraviolet (UV)B-induced intracellular reactive oxygen species (ROS) production. Additionally, S4 inhibited UVB-induced phosphorylation of mitogen-activated protein (MAP) kinases, activator protein-1 (AP-1), and matrix metalloproteinases (MMPs) overexpression. Furthermore, S4 also inhibited UVB-induced Smad7 protein expression and elevated total collagen content in human dermal fibroblasts. For anti-inflammatory activity, S4 inhibited UVB-induced nitric oxide synthase (i-NOS) and cyclooxygenase (COX)-2 protein expression and inhibited nuclear factor-kappaB (NF-ĸB) translocation into the nucleus. S4 ameliorated UVB-induced erythema and wrinkle formation in hairless mice. On histological observation, S4 also ameliorated UVB-induced epidermal hyperplasia and collagen degradation. S4 reduced UVB-induced MMP-1, interleukin (IL)-6, and NF-ĸB expression in the mouse skin. The results indicated that S4 had antiphotoaging and anti-inflammatory activities, protecting skin from premature aging.

Pathogen incursions are a major impediment for global forest health. How pathogens and forest trees coexist over time, without pathogens simply killing their long-lived hosts, is a critical but unanswered question. The Dothistroma Needle Blight pathogen Dothistroma septosporum was introduced into New Zealand in the 1960s and remains a low-diversity, asexual population, providing a unique opportunity to analyze the evolution of a forest pathogen. Isolates of D. septosporum collected from commercial pine forests over 50 years were compared at whole-genome and phenotype levels. Limited genome diversity and increased diversification among recent isolates support the premise of a single introduction event. Isolates from the 1960s show significantly elevated virulence against Pinus radiata seedlings and produce higher levels of the virulence factor dothistromin compared to isolates collected in the 1990s and 2000s. However, later isolates have no increased tolerance to copper, used in fungicide treatments of infested forests and traditionally assumed to be a strong selection pressure. The isolated New Zealand population of this forest pathogen therefore appears to have become less virulent over time, likely in part to maintain the viability of its long-lived host. This finding has broad implications for forest health and highlights the benefits of long-term pathogen surveys.

Based on active heating materials (the phase change microcapsules (microPCMs)) and passive insulating materials (SiO2 aerogel), a new-type multilayer low temperature protective composite fabric (MPF) was designed and manufactured to meet the demands of protection and operation in a short time under a low-temperature environment. Results showed that the MPF consisted of three layers including the fabric layer, the microPCM function layer, and the SiO2 aerogel thermal insulation layer. The differential scanning calorimeter (DSC) results demonstrated that the phase transition enthalpy of the composite was 96.2 J/g during the cooling process. The low-temperature resistance and thermal insulation performance at -50 °C were investigated. The results also demonstrated that the low-temperature resistance time of the MPF was 660 s and the power consumption of the MPFs needed to maintain 37 °C for 10 and 20 min were 629 J and 1872 J, respectively. Compared with the microPCM function layer and the thermal insulation layer, which have the same thickness as the MPF, the low-temperature resistance time of the MPF was prolonged for about 2 and 3 min, respectively. The MPF could provide effective protection of the low-temperature work in a short time and could be applied as potential materials in low-temperature protection.