GENA: A knowledge graph for nutrition and mental health.

While a large number of knowledge graphs have previously been developed by automatically extracting and structuring knowledge from literature, there is currently no such knowledge graph that encodes relationships between food, biochemicals and mental illnesses, even though a large amount of knowledge about these relationships is available in the form of unstructured text in biomedical literature articles. To address this limitation, this article describes the development of GENA - (Graph of mEntal-health and Nutrition Association), a knowledge graph that represents relations between nutrition and mental health, extracted from biomedical abstracts. GENA is constructed from PubMed abstracts that contain keywords relating to chemicals, food, and health. A hybrid named entity recognition (NER) model is firstly applied to these abstracts to identify various entities of interest. Subsequently, a deep syntax-based relation extraction model is used to detect binary relations between the identified entities. Finally, the resulting relations are used to populate the GENA knowledge graph, whose relationships can be accessed in an intuitive and interpretable manner using the Neo4J Database Management System. To evaluate the reliability of GENA, two annotators manually assessed a subset of the extracted relations. The evaluation results show that our methods obtain high precision for the NER task and acceptable precision and relative recall for the relation extraction task. GENA consists of 43,367 relationships that encode information about nutrition and health, of which 94.04% are new relations that are not present in existing ontologies of food and diseases. GENA is constructed based on scientific principles, and has the potential to be used within further applications to contribute towards scientific research within the domain. It is a pioneering knowledge graph in nutrition and mental health, containing a diverse range of relationship types. All of our source code and results are publicly available at https://github.com/ddlinh/gena-db.

Motivations for choosing various food groups based on individual foods.

Understanding "why people eat what they eat" is important for improving the lives of people around the world by helping provide industrial and social solutions for people to have greater pleasure and health from the foods they choose. The objective of this study was to investigate the motivations behind everyday choices of different food groups using a bottom-up approach that targeted the specific choices of foods and beverages people consumed at various times of a day. This study was conducted using an online survey included questions related to demographics, the most recent meal including specific food choices, and a slightly modified Eating Motivation Surveys (2 motivations were added, and Check-All-That-Apply procedure was used), which contained 50 sub-scales to measure 17 motivations including such topics as Liking, Pleasure, Convenience, Health, Price, Variety Seeking etc. A total of 198 participants have completed the surveys. Data were analyzed by Correspondence Analysis. Liking was found to be the strongest motivation that drove people to select all sorts of foods. Need and Hunger and Convenience were the main motivations for baked products, "fast" foods, sausages and meats, and snack foods while Health and Weight Control were found to be the main driving factors for vegetables, fruits & fruit juices, nuts, seeds, dairy & egg, and poultry products. Sweets were linked to Pleasure. For beverages, people were motivated most by Heath and Weight Control to choose water and tea. Coffee was used due to Habits; soda was because of Pleasure and alcoholic was for socialization purposes. This study provided developers, marketers, health educators, etc. With a new method to understand food choice in order to promote better eating.

Fenbendazole and Diisopropylamine Dichloroacetate Exert Synergistic Anti-cancer Effects by Inducing Apoptosis and Arresting the Cell Cycle in A549 Lung Cancer Cells.

BACKGROUND/AIM: Lung cancer is the leading cause of cancer-related mortality worldwide, accounting for approximately 2 million new cases and 1.8 million deaths annually. Standard treatment options include surgery, radiation therapy, chemotherapy, and targeted therapies. Despite advancements over the past 25 years, the prognosis of patients with lung cancer remains poor. This study evaluated the synergistic anticancer effects of fenbendazole (FZ) and diisopropylamine dichloroacetate (DADA) on A549 lung cancer cells. MATERIALS AND METHODS: Fenbendazole (methyl N-(6-phenylsulfanyl-1H-benzimidazol-2-yl) carbamate) is a broad-spectrum benzimidazole anthelmintic commonly used in veterinary medicine. Diisopropylamine Dichloroacetate (DADA), an over-the-counter treatment for chronic liver disease, has demonstrated anti-tumor properties as an inhibitor of pyruvate dehydrogenase kinase. RESULTS: The combination of FZ and DADA exhibited a synergistic effect on inhibiting the proliferation of A549 lung cancer cells. After 48 h of treatment, the FZ-DADA combination produced reactive oxygen species (ROS) and promoted apoptosis by down-regulating Bcl2 and up-regulating BAX protein expression. The combination activated caspase-3, caspase-7, and PARP, further driving apoptosis in A549 cells. The FZ-DADA treatment also induced cell cycle arrest, as evidenced by the inhibition of Cyclin A and Cyclin E proteins. CONCLUSION: The synergistic anticancer effects of the FZ-DADA combination were confirmed at both cellular and protein levels in A549 lung cancer cells. The combination modulates key apoptotic proteins, induces cell cycle arrest, and increases mitochondrial ROS production, suggesting a promising approach for lung cancer treatment that warrants further investigation and development.

Absence of gamma-interferon-inducible lysosomal thiol reductase in melanomas disrupts T cell recognition of select immunodominant epitopes.

Long-lasting tumor immunity requires functional mobilization of CD8+ and CD4+ T lymphocytes. CD4+ T cell activation is enhanced by presentation of shed tumor antigens by professional antigen-presenting cells (APCs), coupled with display of similar antigenic epitopes by major histocompatibility complex class II on malignant cells. APCs readily processed and presented several self-antigens, yet T cell responses to these proteins were absent or reduced in the context of class II+ melanomas. T cell recognition of select exogenous and endogenous epitopes was dependent on tumor cell expression of gamma-interferon-inducible lysosomal thiol reductase (GILT). The absence of GILT in melanomas altered antigen processing and the hierarchy of immunodominant epitope presentation. Mass spectral analysis also revealed GILT's ability to reduce cysteinylated epitopes. Such disparities in the profile of antigenic epitopes displayed by tumors and bystander APCs may contribute to tumor cell survival in the face of immunological defenses.

Clinical characteristics of hand, foot and mouth disease in Daklak Province, Vietnam and associated factors of severe cases.

The Hand, Foot and Mouth Disease (HFMD) outbreaks occurred throughout Daklak province, Vietnam in 2011. This study reviewed all 744 medical records of HFMD patients admitted to Daklak Hospital in 2011 to describe the clinical characteristics of HFMD patients and determined factors associated with severe illness. Among 744 patients, 63 (8.5%) cases were severe. Most (695, 93.4%) of the cases were 3 years old or younger, and 464 (62.4%) were boys. The number of cases peaked between August and November. Most (726, 97.6%) recovered, 17 severe cases (2.3%) were transferred to higher level hospitals, and one death. Symptoms at admission included fever (93.5% had a fever ≥ 38.5 °C), blisters (99.1%), myoclonus (58.5%), and leukocytosis (> 11,300/mm3: 38.8%). Viral cultures were performed for 61 of 63 severe cases, of which 26.2% were positive for Enteroviruses. Multivariable analysis found that oral ulcers (Odds Ratio (OR) 3.74; 95% Confidence Interval (CI) 2.13-6.58), myoclonus (OR 44.75; 95% CI 6.04-331.66) and high white blood cell count (OR 1.08; 95% CI 1.01-1.16 per 1000/mm3 increase) were significantly associated with severe illness. HFMD mainly occurs in children younger than 3 years old and rainy season. Oral ulcers, myoclonus, and leukocytosis should be closely monitored to promptly detect severe cases of HFMD.

Motivations for Food Consumption during Specific Eating Occasions in Turkey.

Several studies in different countries have been conducted to investigate factors affecting food choices. The objective of this study was to understand the motivations of specific food and beverage choices for different eating occasions in a typical diet of the Turkish people. A convenience sample of 141 respondents from seven different geographical regions in Turkey completed an online survey questionnaire that included questions about demographic information and details about their latest eating occasion. Respondents reported all of their motivations for choosing each food/beverage item reported for that specific eating occasion. Results indicated that different motivations played different roles in food choices of people in Turkey. Liking was a key characteristic for all eating occasions, but key natural concerns were even more important at breakfast, and need and hunger were more important for a mid-afternoon snack. Lunch involved additional motivations such as Sociability, Variety Seeking, and Social Norms. In addition to Liking, choices of different food groups were also driven by other motivations such as Habits, Convenience, Need and Hunger, Natural Concerns, and Health. This study helped better understand the current dietary patterns of Turkish people as well as the motives underlying their choices of foods and beverages for different meals and snacks. These findings could be useful for dietary campaigns that aim to improve eating behaviors in Turkey.

Investigation of Fucoidan-Oleic Acid Conjugate for Delivery of Curcumin and Paclitaxel.

Nanoparticles for a specific delivery are likely to be designed for cancer therapeutic effectiveness and improvement. In this study, a fucoidan-oleic acid conjugate was prepared and investigated in terms of loading capacity for poorly water-soluble anti-cancer drugs to maximize effectiveness of the treatment. Fucoidan was used as a hydrophilic portion of an amphiphilic structure for improving cancer therapeutic effects. Paclitaxel and curcumin were chosen as other model drugs loaded in the conjugates. The results showed that self-assembled nanoparticles with different sizes and morphologies could be prepared with two different concentrations of oleic acid as hydrophobic portion. Moreover, loading efficiency and release patterns of these drugs were mainly dependent on the hydrophobic interaction between drugs and oleic acid. It was also revealed that fucoidan and curcumin were released higher at pH 4.5 than at the physiological condition (pH 7.4), thus, facilitating the delivery and maximizing effects of the anticancer agents on cancer cells. On the contrary, paclitaxel from fucoidan nanoparticles was released faster at pH 7.4. The exploration of fucoidan-oleic acid conjugate could be considered as promising nanomedicines for cancer therapeutics.

Disulfide reduction in major histocompatibility complex class II-restricted antigen processing by interferon-gamma-inducible lysosomal thiol reductase.

Constitutively expressed in antigen-presenting cells (APCs), interferon-gamma-inducible lysosomal thiol reductase (GILT) catalyzes disulfide bond reduction under acidic conditions. GILT contains a CXXC motif similar to the WCGH/PCK motif of proteins in the thioredoxin family. This class of enzymes catalyzes, at a neutral pH, dithiol oxidation, disulfide bond reduction, and disulfide bond isomerization. A well-established assay spectrophotometrically measures interchain disulfide bond reduction of insulin via the precipitation of aggregating free B chains. However, the insolubility of insulin at low pH limits the use of this assay. To assess the thiol reductase activity of GILT, we employed an assay that uses denatured [125I]F(ab')2 as a substrate, which is detailed in this article. In addition, we discuss approaches used to demonstrate the mechanism of action of GILT and to identify substrates.

Remodeling of the lectin-EGF-like domain interface in P- and L-selectin increases adhesiveness and shear resistance under hydrodynamic force.

Crystal structures of the lectin and epidermal growth factor (EGF)-like domains of P-selectin show 'bent' and 'extended' conformations. An extended conformation would be 'favored' by forces exerted on a selectin bound at one end to a ligand and at the other end to a cell experiencing hydrodynamic drag forces. To determine whether the extended conformation has higher affinity for ligand, we introduced an N-glycosylation site to 'wedge open' the interface between the lectin and EGF-like domains of P-selectin. This alteration increased the affinity of P-selectin for its ligand P-selectin glycoprotein 1 (PSGL-1) and thereby the strength of P-selectin-mediated rolling adhesion. Similarly, an asparagine-to-glycine substitution in the lectin-EGF-like domain interface of L-selectin enhanced rolling adhesion under shear flow. Our results demonstrate that force, by 'favoring' an extended selectin conformation, can strengthen selectin-ligand bonds.

Role of the C-terminal propeptide in the activity and maturation of gamma -interferon-inducible lysosomal thiol reductase (GILT).

gamma-Interferon-inducible lysosomal thiol reductase (GILT) is constitutively expressed in antigen-presenting cells. GILT facilitates unfolding of endocytosed antigens in MHC class II-containing compartments by enzymatically reducing disulfide bonds. The enzyme is synthesized as a 35-kDa precursor. Although a fraction of the precursor is secreted as a disulfide-linked dimer, the majority is directed via the mannose-6-phosphate receptor pathway to endocytic compartments where its N- and C-terminal propeptides are cleaved to generate the 30-kDa mature form. Both precursor and mature GILT reduce disulfide bonds with an acidic pH optimum. In this report, we show that the cysteine residues in the C-terminal propeptide, Cys-211 and Cys-222, serve key structural roles. Mutation of Cys-222 abolishes disulfide-linked dimerization of precursor GILT and decreases the efficiency of GILT maturation. Mutation of Cys-211 results in both impaired intracellular maturation and loss of enzymatic activity of the precursor form at an acidic pH. A similar phenotype was obtained upon mutation of Cys-200, which is retained in the mature form. Cys-200 and Cys-211 seem to form a disulfide bond that links the propeptide and the mature enzyme until reduction in the lysosome. This disulfide bridge is essential for stability of the enzyme at low pH and for its proper maturation in vivo.