bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of a High-Intensity Dietary Intervention on Changes in Dietary Intake and Eating Pathology during a Multicomponent Adolescent Obesity Intervention
Authors: Raynor Hollie A. , Mazzeo Suzanne E. , LaRose Jessica Gokee , Adams Elizabeth L. , Thornton Laura M. , Caccavale Laura J. , Bean Melanie K.
Published: May 2021

Concerns remain about dietary changes during pediatric obesity treatment and eating pathology, which have not been investigated. This secondary data analysis from a randomized clinical trial examined associations between adolescents’ changes in energy intake and diet quality during obesity treatment with post-treatment eating pathology. Adolescents (N = 82: 13.7 ± 1.2 y, 34.9 ± 7.0 kg/m2, 63.4% female, 46.3% black) received TEENS+, a 4-month multicomponent intervention. TEENS+ provided individualized dietary goals (1200–1800 kcal/day; number of “Go” foods/day (low-energy, high-nutrient-dense foods)). At 0 and 4 months, 3-day food records assessed energy intake and diet quality (Healthy Eating Index 2015 (HEI-2015)). Two HEI-2015 subscores were created: components to increase (increase), and components to limit (decrease). The Eating Disorder Examination Questionnaire measured eating pathology (total score and subscales: restraint; and eating, weight, and shape concern). Corrected p-values are reported as q-values. Energy intake decreased (−292 ± 418 kcal/day; q < 0.001), while diet quality improved during treatment (total HEI-2015 (4.5 ± 15.1; q = 0.034) and increase (3.3 ± 9.4; q = 0.011)). Restraint increased (+0.6 ± 1.4; q < 0.001), whereas shape (−0.5 ± 1.3; q = 0.004) and weight (−0.5 ± 1.4; q = 0.015) concerns decreased. Greater decreases in energy intake were associated with greater restraint post-treatment (F = 17.69; q < 0.001). No other significant associations were observed. Changes in adolescents’ dietary intake during obesity treatment were unrelated to increased shape, weight, or eating concerns post-treatment.
Impact of Fatty Acid Supplementation on Cognitive Performance among United States (US) Military Officers: The Ranger Resilience and Improved Performance on Phospholipid-Bound Omega-3’s (RRIPP-3) Study
Authors: Marriott Bernadette P. , Turner Travis H. , Hibbeln Joseph R. , Newman Jill C. , Pregulman Marcie , Malek Angela M. , Malcolm Robert J. , Burbelo Gregory A. , Wismann Jeffrey W.
Published: May 2021

Studies have assessed omega-3 fatty acids and cognitive decline among older adults and cognitive development among children, although less is known about cognitive or neurological effects among young adults. We examined whether omega-3 supplementation from krill oil could improve cognition and resilience among young military officers compared to a control. This double-blind, placebo-controlled trial enrolled 555 officers (mean age 23.4 ± 2.8, 98.6% male) entering the United States (US) Army Infantry Basic Officer Leaders Course (IBOLC) with the intention to complete the US Ranger Course. Volunteer participants consumed eight dietary supplements daily of krill oil containing 2.3 g omega-3 or control (macadamia nut oil) over an approximate 20-week period. Cognitive functioning, resilience, and mood were assessed during a well-rested period at approximately 14 weeks and after a battlefield simulation at 16 weeks. Blood spot samples were collected to monitor compliance and dietary intake was assessed. All hypotheses were tested using both ‘Intention to Treat’ (ITT) and ‘As Per Protocol’ (APP) approaches. Of the 555 randomized individuals, 245 (44.1%) completed the study. No statistically significant group-by-time interactions indicating treatment effect were found on any outcomes. Poor compliance was indicated by lower than expected omega-3 elevations in the treatment group, and may have contributed to a failure to detect a response.
Alcohol Use as a Function of Physical Activity and Golfing Motives in a National Sample of United States Golfers
Authors: Courtney Jimikaye , Handley Eric , Pagoto Sherry , Russell Michael , Conroy David E.
Published: May 2021

Alcohol and physical inactivity are risk factors for a variety of cancer types. However, alcohol use often co-occurs with physical activity (PA), which could mitigate the cancer-prevention benefits of PA. Alcohol is integrated into the culture of one of the most popular physical activities for adults in the United States (U.S.), golf. This study examined how alcohol use was associated with total PA, golf-specific PA, and motives for golfing in a national sample of golfers in the U.S. Adult golfers (n = 338; 51% male, 81% White, 46 ± 14.4 years) self-reported alcohol use, golfing behavior and motives, and PA. Most (84%) golfers consumed alcohol, averaging 7.91 servings/week. Golf participation, including days/week, holes/week, and practice hours/week, was not associated with alcohol use. Golfers with stronger social motives were 60% more likely to consume alcohol. Weekly walking (incident risk ratio (IRR) = 7.30), moderate-to-vigorous PA (MVPA; IRR = 5.04), and total PA (IRR = 4.14) were associated with more alcohol servings/week. Golfers’ alcohol use may be higher than the general adult population in the U.S. and contributes 775 extra kilocalories/week, a surplus that may offset PA-related energy expenditure and cancer-protective effects. Alcohol use interventions targeting golfers may facilitate weight loss and reduce cancer risk, especially for golfers motivated by social status.
Probiotic and Functional Properties of Limosilactobacillus reuteri INIA P572
Authors: Diez-Echave Patricia , Martín-Cabrejas Izaskun , Garrido-Mesa José , Langa Susana , Vezza Teresa , Landete José M. , Hidalgo-García Laura , Algieri Francesca , Mayer Melinda J. , Narbad Arjan , García-Lafuente Ana , Medina Margarita , Rodríguez-Nogales Alba , Rodríguez-Cabezas María Elena , Gálvez Julio , Arqués Juan L.
Published: May 2021

Limosilactobacillus reuteri INIA P572 is a strain able to produce the antimicrobial compound reuterin in dairy products, exhibiting a protective effect against some food-borne pathogens. In this study, we investigated some probiotic properties of this strain such as resistance to gastrointestinal passage or to colonic conditions, reuterin production in a colonic environment, and immunomodulatory activity, using different in vitro and in vivo models. The results showed a high resistance of this strain to gastrointestinal conditions, as well as capacity to grow and produce reuterin in a human colonic model. Although the in vitro assays using the RAW 264.7 macrophage cell line did not demonstrate direct immunomodulatory properties, the in vivo assays using a Dextran Sulphate Sodium (DSS)-induced colitic mice model showed clear immunomodulatory and protective effects of this strain.
Effects of School-Based Interventions on Reducing Sugar-Sweetened Beverage Consumption among Chinese Children and Adolescents
Authors: Zhu Zhenni , Luo Chunyan , Qu Shuangxiao , Wei Xiaohui , Feng Jingyuan , Zhang Shuo , Wang Yinyi , Su Jin
Published: May 2021

We set up a series of school-based interventions on the basis of an ecological model targeting sugar-sweetened beverage (SSB) reduction in Chinese elementary and middle schools and evaluated the effects. A total of 1046 students from Chinese elementary and middle schools were randomly recruited in an intervention group, as were 1156 counterparts in a control group. The interventions were conducted in the intervention schools for one year. The participants were orally instructed to answer all the questionnaires by themselves at baseline and after intervention. The difference in difference statistical approach was used to identify the effects exclusively attributable to the interventions. There were differences in grade composition and no difference in sex distribution between the intervention and control groups. After adjusting for age, sex, and group differences at baseline, a significant reduction in SSB intake was found in the intervention group post intervention, with a decrease of 35.0 mL/day (p = 0.034). Additionally, the frequency of SSB consumption decreased by 0.2 times/day (p = 0.071). The students in the elementary schools with interventions significantly reduced their SSB intake by 61.6 mL/day (p = 0.002) and their frequency of SSB consumption by 0.3 times/day (p = 0.017) after the intervention. The boys in the intervention group had an intervention effect of a 50.2 mL/day reduction in their SSB intake (p = 0.036). School-based interventions were effective in reducing SSB consumption, especially among younger ones. The boys were more responsive to the interventions than the girls. (ChiCTR, ChiCTR1900020781.)
Social Representations of Drinking Water in Schoolchildren and Parents from Two Schools in Zapopan, Mexico
Authors: Corona-Romero Alejandra María , Bernal-Orozco María Fernanda , Grover-Baltazar Gabriela Alejandra , Vizmanos Barbara
Published: May 2021

Childhood obesity and children being overweight has increased recently; although they are multi-causal problems, an unhealthy diet is a critical component. In Mexico, drinking water consumption in children from 9 to 18 years only reaches 30% of total fluid consumption. The aim of our study was to describe the social representations (SR) of drinking water in school-children and parents of two schools in Zapopan, Mexico. Associative free listing was used as an information gathering technique. Schoolchildren aged 8 to 12 years (n = 50) and parents (n = 23) from two elementary schools were selected by a convenience sampling from April to June 2015. A similarity analysis was performed using the co-occurrence index; with this, a similarity graph was obtained. Prototypical analysis was performed to explore the structure of the SR. Three dimensions were described in the children’s SR: a functional dimension related to health and nutrition, a practical dimension that describes the instruments used for its consumption, and a theoretical dimension that specifies the characteristics of water and its relationship with nature. In the parents’ SR, a functional dimension was also found; another dimension was described regarding the integral well-being that drinking water provides. A practical dimension describes the features related to its consumption. The investigation describes the structure of the water SR, which help to contextualize and explain the actions of schoolchildren and their parents regarding drinking water consumption.
Impact of Body Mass Index on the Survival of Patients with Sepsis with Different Modified NUTRIC Scores
Authors: Tsai Yi-Hsuan , Lin Chiung-Yu , Chen Yu-Mu , Chang Yu-Ping , Hung Kai-Yin , Chang Ya-Chun , Chen Hung-Cheng , Huang Kuo-Tung , Chen Yung-Che , Wang Yi-Hsi , Wang Chin-Chou , Lin Meng-Chih , Fang Wen-Feng
Published: May 2021

Nutritional status affects the survival of patients with sepsis. This retrospective study analyzed the impact of body mass index (BMI) and modified nutrition risk in critically ill (mNUTRIC) scores on survival of these patients. Data of 1291 patients with sepsis admitted to the intensive care unit (ICU) were extracted. The outcomes were mortality, duration of stay, ICU stay, and survival curve for 90-day mortality. Logistic regression analysis was performed to examine the risk factors for mortality. Cytokine and biomarker levels were analyzed in 165 patients. The 90-day survival of underweight patients with low mNUTRIC scores was significantly better than that of normal-weight patients with low mNUTRIC scores (70.8% vs. 58.3%, respectively; p = 0.048). Regression model analysis revealed that underweight patients with low mNUTRIC scores had a lower risk of mortality (odds ratio = 0.557; p = 0.082). Moreover, normal-weight patients with low mNUTRIC scores had the lowest human leukocyte antigen DR (HLA-DR) level on days 1 (underweight vs. normal weight vs. overweight: 94.3 vs. 82.1 vs. 94.3, respectively; p = 0.007) and 3 (91.8 vs. 91.0 vs. 93.2, respectively; p = 0.047). Thus, being underweight may not always be harmful if patients have optimal clinical nutritional status. Additionally, HLA-DR levels were the lowest in patients with low survival.
Bee Pollen: Current Status and Therapeutic Potential
Authors: Khalifa Shaden A. M. , Elashal Mohamed H. , Yosri Nermeen , Du Ming , Musharraf Syed G. , Nahar Lutfun , Sarker Satyajit D. , Guo Zhiming , Cao Wei , Zou Xiaobo , Abd El-Wahed Aida A. , Xiao Jianbo , Omar Hany A. , Hegazy Mohamed-Elamir F. , El-Seedi Hesham R.
Published: May 2021

Bee pollen is a combination of plant pollen and honeybee secretions and nectar. The Bible and ancient Egyptian texts are documented proof of its use in public health. It is considered a gold mine of nutrition due to its active components that have significant health and medicinal properties. Bee pollen contains bioactive compounds including proteins, amino acids, lipids, carbohydrates, minerals, vitamins, and polyphenols. The vital components of bee pollen enhance different bodily functions and offer protection against many diseases. It is generally marketed as a functional food with affordable and inexpensive prices with promising future industrial potentials. This review highlights the dietary properties of bee pollen and its influence on human health, and its applications in the food industry.
Does Branched-Chain Amino Acids (BCAAs) Supplementation Attenuate Muscle Damage Markers and Soreness after Resistance Exercise in Trained Males? A Meta-Analysis of Randomized Controlled Trials
Authors: Khemtong Chutimon , Kuo Chia-Hua , Chen Chih-Yen , Jaime Salvador J. , Condello Giancarlo
Published: May 2021

Previous studies have reported the positive effects of branched-chain amino acids (BCAAs) supplementation on lowering plasma markers of muscle damage and subjective soreness after resistance exercise. However, a variety of factors can potentially moderate its efficacy. This meta-analysis aimed to summarize the evidence regarding the effect of BCAAs supplementation on plasma muscle damage markers and soreness after resistance exercise in only trained males, by considering the plasma lactate dehydrogenase (LDH) and creatine kinase (CK). Randomized controlled trials were identified through a computerized literature search for the period 2010–2020. The pooled data were analyzed with the random-effects model and heterogeneity using I2. Cochrane Collaboration tools was used for the assessment of risk of bias. Nine studies met the inclusion criteria. A positive effect was found for CK at <24, 24, and 48 h after exercise and for muscle soreness at <24 h only. However, the positive effect was not evident for plasma LDH at any follow-up time. Different outcomes for post-exercise responses may suggest that BCAAs supplementation can attenuate muscle damage and ameliorate muscle soreness after resistance exercise in trained males.
Human Milk Concentrations of Minerals, Essential and Toxic Trace Elements and Association with Selective Medical, Social, Demographic and Environmental Factors
Authors: Mandiá Natalia , Bermejo-Barrera Pilar , Herbello Paloma , López-Suárez Olalla , Fraga Jose M. , Fernández-Pérez Cristina , Couce María L.
Published: May 2021

This study aims to quantify concentrations of minerals and trace elements in human milk (HM) and infant formula (IF) and evaluate associations with medical, social, environmental, and demographic variables. A prospective, case series study of 170 nursing mothers was made. HM samples were obtained from full-term (colostrum, intermediate and mature HM) and preterm (mature HM) mothers. Variables of interest were assessed by a questionnaire. For comparison, IF samples (n = 30) were analyzed in a cross-sectional study. Concentrations of 35 minerals, essential and toxic trace elements were quantified, 5 for the first time: thallium in HM and IF; strontium in preterm HM; and gallium, lithium and uranium in IF. In preterm and full-term HM, levels of selenium (p < 0.001) were significantly lower than recommended and were associated with low birth weight (p < 0.002). Cesium and strontium concentrations were significantly higher than recommended (p < 0.001). Associations were observed between arsenic and residence in an urban area (p = 0.013), and between lead and smoking (p = 0.024) and well-water consumption (p = 0.046). In IF, aluminum, vanadium, and uranium levels were higher than in HM (p < 0.001); uranium, quantified for the first time, was 100 times higher in all types of IF than in HM. Our results indicate that concentrations of most trace elements were within internationally accepted ranges for HM and IF. However, preterm infants are at increased risk of nutritional deficiencies and toxicity. IF manufacturers should reduce the content of toxic trace elements.
Phytate and Butyrate Differently Influence the Proliferation, Apoptosis and Survival Pathways in Human Cancer and Healthy Colonocytes
Authors: Markiewicz Lidia Hanna , Ogrodowczyk Anna Maria , Wiczkowski Wiesław , Wróblewska Barbara
Published: May 2021

The colonic epithelium is never exposed to a single factor, therefore studies on the effect of combinations of factors naturally and persistently present in the intestines are of special importance for understanding the phenomena occurring at this place. The aim of the study was to investigate the combined effect of 1 mM phytate and 1 mM butyrate (PA1B1) on cell lines derived from cancer (HCT116 and HT-29) and healthy (NCM460D) human colonic epithelium. Colorimetric and flow cytometry methods were used to determine the proliferation rate, cell cycle, and apoptosis. Selected markers of proliferation, inflammatory, and survival pathways were investigated at the mRNA and/or protein level. The combination of phytate and butyrate disturbed the cell cycle and triggered apoptosis and/or death in both studied cancer colonocytes to a higher extent compared to healthy colonocytes. Moreover, in healthy colonocytes, phytate activated the survival pathway without stimulation of inflammatory response. This may indicate that the response of healthy colonocytes to phytate protects colonic epithelium from the loss of integrity and tightness that would occur if inflammation developed. Based on the obtained results we postulate that studies on both cancer and/or healthy colonocytes should be carried out in the presence of butyrate as the permanent component of colonic contents. This should be of special importance when anti-proliferative/pro-apoptotic activity or inflammatory status of colonocytes is to be investigated.
The Health Behaviours of Students from Selected Countries—A Comparative Study
Authors: Lesińska-Sawicka Małgorzata , Pisarek Ewa , Nagórska Małgorzata
Published: May 2021

Health behaviour defined as any behaviour that may affect an individual’s physical and mental health or any behaviour that an individual believes may affect their physical health. It is strongly related to their culture and plays a major role in shaping all health and illness-related behaviour. The purpose of the study was to compare and evaluate the lifestyles of students from multiple countries. The proposed work will determine the deficits in health behaviors undertaken by students. The survey was carried out from December 2016 to March 2017 comprising 532 students from Poland, Hungary, Turkey, and Greece. The sample was selected using the snowball method: a link to the online questionnaire was sent to students from the given countries via the Internet. For some participants, who did not have access to the online questionnaire, printed copies were used instead. As a method was used a diagnostic survey and the survey technique. The opinions of students were measured using the 5-level Likert scale with a neutral option. Students undertook health-promoting activities, but also list behaviours that did not contribute to strengthening their health. Students were shown to have the greatest problems with physical health behaviours and health prevention. There were noticeable differences in the lifestyle of students from different countries.
Modelling Dispersion Compensation in a Cascaded-Fiber-Feedback Optical Parametric Oscillator
Authors: Allan Ewan , Ballantine Craig , Robarts Sebastian C. , Bajek David , McCracken Richard A.
Published: May 2021

Fiber-feedback optical parametric oscillators (OPOs) incorporate intracavity fibers to provide a compact high-energy wavelength-tunable laser platform; however, dispersive effects can limit operation to the sub-picosecond regime. In this research article, we modeled pulse propagation through systems of cascaded fibers, incorporating SMF-28 and ultra-high numerical aperture (UHNA) fibers with complementary second-order dispersion coefficients. We found that the pulse duration upon exiting the fiber system is dominated by uncompensated third-order effects, with UHNA7 presenting the best opportunity to realise a cascaded-fiber-feedback OPO.
Culture of Mycobacterium smegmatis in Different Carbon Sources to Induce In Vitro Cholesterol Consumption Leads to Alterations in the Host Cells after Infection: A Macrophage Proteomics Analysis
Authors: de Lima Jaqueline Batista , da Silva Fonseca Lana Patricia , Xavier Luciana Pereira , de Matos Macchi Barbarella , Cassoli Juliana Silva , da Silva Edilene Oliveira , da Silva Valadares Rafael Borges , do Nascimento José Luiz Martins , Santos Agenor Valadares , de Sena Chubert Bernardo Castro
Published: May 2021

During tuberculosis, Mycobacterium uses host macrophage cholesterol as a carbon and energy source. To mimic these conditions, Mycobacterium smegmatis can be cultured in minimal medium (MM) to induce cholesterol consumption in vitro. During cultivation, M. smegmatis consumes MM cholesterol and changes the accumulation of cell wall compounds, such as PIMs, LM, and LAM, which plays an important role in its pathogenicity. These changes lead to cell surface hydrophobicity modifications and H2O2 susceptibility. Furthermore, when M. smegmatis infects J774A.1 macrophages, it induces granuloma-like structure formation. The present study aims to assess macrophage molecular disturbances caused by M. smegmatis after cholesterol consumption, using proteomics analyses. Proteins that showed changes in expression levels were analyzed in silico using OmicsBox and String analysis to investigate the canonical pathways and functional networks involved in infection. Our results demonstrate that, after cholesterol consumption, M. smegmatis can induce deregulation of protein expression in macrophages. Many of these proteins are related to cytoskeleton remodeling, immune response, the ubiquitination pathway, mRNA processing, and immunometabolism. The identification of these proteins sheds light on the biochemical pathways involved in the mechanisms of action of mycobacteria infection, and may suggest novel protein targets for the development of new and improved treatments.
Genetic and Transcriptomic Variations for Amoxicillin Resistance in Helicobacter pylori under Cryopreservation
Authors: Han Xiurui , Zhang Yiyao , He Lihua , Fan Ruyue , Sun Lu , Fan Dongjie , Gong Yanan , Chen Xiaoli , You Yuanhai , Zhao Fei , Zhang Maojun , Zhang Jianzhong
Published: May 2021

Some amoxicillin-resistant strains of H. pylori show a sharp decrease in amoxicillin resistance after freezing. In China, most clinical gastric mucosal specimens are frozen and transported for isolation and drug susceptibility testing for H. pylori, which may lead to an underestimation of the amoxicillin resistance. The objective of this study is to investigated reasons for the decreased amoxicillin resistance after cryopreservation. A high-level amoxicillin-resistant clone (NX24r) was obtained through amoxicillin pressure screening. After cryopreservation at −80 °C for 3 months, the minimum inhibitory concentration (MIC) of NX24r was reduced sharply. Mutations and changes of transcriptome were analyzed after amoxicillin screening and cryopreservation. Mutations in PBP1 (I370T, E428K, T556S) and HefC (M337K, L378F, D976V) were detected in NX24r, which may be the main reason for the induced amoxicillin resistance. No mutations were found in PBP1 or HefC after cryopreservation. However, transcriptome analysis showed that down-regulated genes in the cryopreserved clone were significantly enriched in plasma membrane (GO:0005886), including lepB, secD, gluP, hp0871 and hp1071. These plasma membrane genes are involved in the biosynthesis and transport function of the membrane. The decreased amoxicillin resistance after cryopreservation may be related to the down-regulation of genes involved in membrane structure and transport function.
Salivarian Trypanosomes Have Adopted Intricate Host-Pathogen Interaction Mechanisms That Ensure Survival in Plain Sight of the Adaptive Immune System
Authors: Magez Stefan , Pinto Torres Joar Esteban , Oh Seoyeon , Radwanska Magdalena
Published: May 2021

Salivarian trypanosomes are extracellular parasites affecting humans, livestock and game animals. Trypanosoma brucei rhodesiense and Trypanosoma brucei gambiense are human infective sub-species of T. brucei causing human African trypanosomiasis (HAT—sleeping sickness). The related T. b. brucei parasite lacks the resistance to survive in human serum, and only inflicts animal infections. Animal trypanosomiasis (AT) is not restricted to Africa, but is present on all continents. T. congolense and T. vivax are the most widespread pathogenic trypanosomes in sub-Saharan Africa. Through mechanical transmission, T. vivax has also been introduced into South America. T. evansi is a unique animal trypanosome that is found in vast territories around the world and can cause atypical human trypanosomiasis (aHT). All salivarian trypanosomes are well adapted to survival inside the host’s immune system. This is not a hostile environment for these parasites, but the place where they thrive. Here we provide an overview of the latest insights into the host-parasite interaction and the unique survival strategies that allow trypanosomes to outsmart the immune system. In addition, we review new developments in treatment and diagnosis as well as the issues that have hampered the development of field-applicable anti-trypanosome vaccines for the implementation of sustainable disease control.
Elucidation of the Molecular Pathways Involved in the Protective Effects of AUY-922 in LPS-Induced Inflammation in Mouse Lungs
Authors: Akhter Mohammad S. , Uddin Mohammad A. , Kubra Khadeja-Tul , Barabutis Nektarios
Published: May 2021

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) cause thousands of deaths every year and are associated with high mortality rates (~40%) due to the lack of efficient therapies. Understanding the molecular mechanisms associated with those diseases will most probably lead to novel therapeutics. In the present study, we investigated the effects of the Hsp90 inhibitor AUY-922 in the major inflammatory pathways of mouse lungs. Mice were treated with LPS (1.6 mg/kg) via intratracheal instillation for 24 h and were then post-treated intraperitoneally with AUY-922 (10 mg/kg). The animals were examined 48 h after AUY-922 injection. LPS activated the TLR4-mediated signaling pathways, which in turn induced the release of different inflammatory cytokines and chemokines. AUY-922 suppressed the LPS-induced inflammation by inhibiting major pro-inflammatory pathways (e.g., JAK2/STAT3, MAPKs), and downregulated the IL-1β, IL-6, MCP-1 and TNFα. The expression levels of the redox regulator APE1/Ref1, as well as the DNA-damage inducible kinases ATM and ATR, were also increased after LPS treatment. Those effects were counteracted by AUY-922. Interestingly, this Hsp90 inhibitor abolished the LPS-induced pIRE1α suppression, a major component of the unfolded protein response. Our study elucidates the molecular pathways involved in the progression of murine inflammation and supports our efforts on the development of new therapeutics against lung inflammatory diseases and sepsis.
Effect of Neuropeptide S Administration on Ultrasonic Vocalizations and Behaviour in Rats with Low vs. High Exploratory Activity
Authors: Kõiv Kadri , Matrov Denis , Uusen Trine , Harro Jaanus
Published: May 2021

Neuropeptide S (NPS) is a peptide neurotransmitter that in animal studies promotes wakefulness and arousal with simultaneous anxiety reduction, in some inconsistency with results in humans. We examined the effect of NPS on rat ultrasonic vocalizations (USV) as an index of affective state and on behaviour in novel environments in rats with persistent inter-individual differences in exploratory activity. Adult male Wistar rats were categorised as of high (HE) or low (LE) exploratory activity and NPS was administered intracerebroventricularly (i.c.v.) at a dose of 1.0 nmol/5 µL, after which USVs were recorded in the home-cage and a novel standard housing cage, and behaviour evaluated in exploration/anxiety tests. NPS induced a massive production of long and short 22 kHz USVs in the home cage that continued later in the novel environment; no effect on 50 kHz USVs were found. In LE-rats, the long 22 kHz calls were emitted at lower frequencies and were louder. The effects of NPS on behaviour appeared novelty- and test-dependent. NPS had an anxiolytic-like effect in LE-rats only in the elevated zero-maze, whereas in HE-rats, locomotor activity in the zero-maze and in a novel standard cage was increased. Thus NPS appears as a psychostimulant peptide but with a complex effect on dimensions of affect.
Development and Bio-Predictive Evaluation of Biopharmaceutical Properties of Sustained-Release Tablets with a Novel GPR40 Agonist for a First-in-Human Clinical Trial
Authors: Juszczyk Ewelina , Kisło Kamil , Żero Paweł , Tratkiewicz Ewa , Wieczorek Maciej , Paszkowska Jadwiga , Banach Grzegorz , Wiater Marcela , Hoc Dagmara , Garbacz Grzegorz , Sczodrok Jaroslaw , Danielak Dorota
Published: May 2021

Sustained-release (SR) formulations may appear advantageous in first-in-human (FIH) study of innovative medicines. The newly developed SR matrix tablets require prolonged maintenance of API concentration in plasma and should be reliably assessed for the risk of uncontrolled release of the drug. In the present study, we describe the development of a robust SR matrix tablet with a novel G-protein-coupled receptor 40 (GPR40) agonist for first-in-human studies and introduce a general workflow for the successful development of SR formulations for innovative APIs. The hydrophilic matrix tablets containing the labeled API dose of 5, 30, or 120 mg were evaluated with several methods: standard USP II dissolution, bio-predictive dissolution tests, and the texture and matrix formation analysis. The standard dissolution tests allowed preselection of the prototypes with the targeted dissolution rate, while the subsequent studies in physiologically relevant conditions revealed unwanted and potentially harmful effects, such as dose dumping under an increased mechanical agitation. The developed formulations were exceptionally robust toward the mechanical and physicochemical conditions of the bio-predictive tests and assured a comparable drug delivery rate regardless of the prandial state and dose labeled. In conclusion, the introduced development strategy, when implemented into the development cycle of SR formulations with innovative APIs, may allow not only to reduce the risk of formulation-related failure of phase I clinical trial but also effectively and timely provide safe and reliable medicines for patients in the trial and their further therapy.
Assessment of Vehicle Volatility and Deposition Layer Thickness in Skin Penetration Models
Authors: Hamadeh Abdullah , Troutman John , Edginton Andrea N.
Published: May 2021

Systemic disposition of dermally applied chemicals is often formulation-dependent. Rapid evaporation of the vehicle can result in crystallization of active compounds, limiting their degree of skin penetration. In addition, the choice of vehicle can affect the permeant’s degree of penetration into the stratum corneum. The aim of this study is to build a predictive, mechanistic, dermal absorption model that accounts for vehicle-specific effects on the kinetics of permeant transport into skin. An existing skin penetration model is extended to explicitly include the effect of vehicle volatility over time. Using in vitro measurements of skin penetration by chemicals applied in both a saline and an ethanol solvent, the model is optimized to learn two vehicle-specific quantities: the solvent evaporation rate and the extent of permeant deposition into the upper stratum corneum immediately following application. The dermal disposition estimates of the trained model are subsequently compared against those of the original model using further in vitro measurements. The trained model showed a 1.5-fold improvement and a 19-fold improvement in overall goodness of fit among compounds tested in saline and ethanol solvents, respectively. The proposed model structure can thus form a basis for in vitro to in vivo extrapolations of dermal disposition for skin formulations containing volatile components.
The Development of an In Vitro Horizontal Diffusion Cell to Monitor Nasal Powder Penetration Inline
Authors: Gieszinger Péter , Kiss Tamás , Szabó-Révész Piroska , Ambrus Rita
Published: May 2021

The development of in vitro investigation models could be important using sensitive and fast methods during formulation. Intranasal applied drugs (meloxicam, lamotrigine, and levodopa) avoid the gastrointestinal tract and can achieve higher bioavailability, therefore a penetration extent is a key property. In this study, the in vitro adaptability of a modified horizontal diffusion cell was tested by using these model active pharmaceutical ingredients (APIs). The special factors consisted of the volume of the chambers, the arrangement of the stirrers, the design of probe input for real-time analysis and decreased membrane area. Membranes were impregnated by isopropyl myristate and by using phosphate buffer to evaluate the effect of API hydrophilicity on the diffusion properties. The lipophilicity of the API was proportional to the penetration extent through isopropyl myristate-impregnated membranes compared with buffer-soaked membranes. After evaluating the arithmetic mean of standard relative deviations and the penetrated extent of APIs at 15 min, Metricel® could be suggested for levodopa and meloxicam, and Whatman™ for lamotrigine. The modified model is suitable for inline, real-time detection, at nasal conditions, using small volumes of phases, impregnated membrane, to monitor the diffusion of the drug and to determine its concentration in the acceptor and donor phases.
Engineering Genetic Systems for Treating Mitochondrial Diseases
Authors: Jang Yoon-ha , Ahn Sae Ryun , Shim Ji-yeon , Lim Kwang-il
Published: May 2021

Mitochondria are intracellular energy generators involved in various cellular processes. Therefore, mitochondrial dysfunction often leads to multiple serious diseases, including neurodegenerative and cardiovascular diseases. A better understanding of the underlying mitochondrial dysfunctions of the molecular mechanism will provide important hints on how to mitigate the symptoms of mitochondrial diseases and eventually cure them. In this review, we first summarize the key parts of the genetic processes that control the physiology and functions of mitochondria and discuss how alterations of the processes cause mitochondrial diseases. We then list up the relevant core genetic components involved in these processes and explore the mutations of the components that link to the diseases. Lastly, we discuss recent attempts to apply multiple genetic methods to alleviate and further reverse the adverse effects of the core component mutations on the physiology and functions of mitochondria.
Impact of Mixing on Content Uniformity of Thin Polymer Films Containing Drug Micro-Doses
Authors: Buyukgoz Guluzar G. , Castro Jeremiah N. , Atalla Andrew E. , Pentangelo John G. , Tripathi Siddharth , Davé Rajesh N.
Published: May 2021

The impact of mixer type and critical process parameters (CPPs) on critical quality attributes (CQAs), including the drug content uniformity (CU) of slurry-cast polymer films loaded with micro-sized poorly water-soluble drugs were investigated. Previously untested hypothesis was that the best mixer at suitable CPPs promotes uniform drug dispersion within film precursors leading to acceptable dried-film CU at low, ~0.6 wt% drug concentrations. Taguchi design was utilized to select the best of three mixers; low-shear impeller, high-shear planetary, and high-intensity vibrational, for dried-film drug concentration of ~23 wt%. As-received fenofibrate, a model poorly water-soluble drug (~6 µm) was directly mixed with the hydroxypropyl methylcellulose (HPMC) and glycerin aqueous solution. Impeller and planetary mixers yielded desirable film relative standard deviation (RSD), while vibrational mixer could not. For the lowest dried-film drug concentration of ~0.6 wt%, only planetary mixer yielded RSD <6%. The precursor drug homogeneity was a sufficient but not a necessary condition for achieving dried-film RSD <6%. Thus, proper selection of mixer and its CPPs assured desirable film CQAs. However, minor drug particle aggregation was identified via re-dispersion testing which also led to incomplete drug release.
The Novel Use of PVP K30 as Templating Agent in Production of Porous Lactose
Authors: Zhu Wei-Feng , Zhu Lin , Li Zhe , Wu Wen-Ting , Guan Yong-Mei , Chen Li-Hua , Mao Zhi-Xuan , Ming Liang-Shan
Published: May 2021

It is necessary to prepare porous lactose in order to improve the dissolution behavior of insoluble active ingredient. In this study, polyvinylpyrrolidone K30 (PVP K30) was firstly utilized as a templating agent with different use levels in preparing porous lactose. Then, the physical properties were profoundly characterized. Finally, the porous lactose was also employed as a health functional food/drug carrier to explore the effect on the dissolution behavior of curcumin. The results confirmed that (i) porous lactose was successfully prepared using PVP K30 as templating agent; (ii) PVP K30 significantly improved the yield of lactose in the spray drying; (iii) the improved powder properties of porous lactose were more conducive to the downstream operating process for the preparation of health functional food or drug; and (iv) the porous lactose significantly improved the dissolution behavior of curcumin. Therefore, the results obtained are beneficial to boosting the development of porous materials.
From Reality without Mysteries to the Mystery of the World: Marilena Chaui’s Reading of Spinoza’s Tractatus Theologico-Politicus
Authors: Magno Viviane
Published: May 2021

This article offers an overview of Marilena Chaui’s reading of the Tractatus Theologico-Politicus (TTP). Chaui has published numerous books and essays on Baruch Spinoza. Her two-volume study The Nerve of Reality is the culmination of a decades-long engagement with the Dutch philosopher, and her research has been a valuable resource for generations of Latin American scholars. From this extensive output, we focus on Chaui’s main texts on the theological-political, concentrating on her analysis of the concept of superstition and the philosophical language of the TTP, which Chaui calls a “counter-discourse”. Spinoza’s enduring relevance for the interpretation of contemporary phenomena is clarified by Chaui’s analysis of the TTP, which establishes a fundamentally political understanding of superstition.
The Relevance of a Physiological-Stage Approach Study of the Molecular and Environmental Factors Regulating Seed Germination in Wild Plants
Authors: Gómez-Maqueo Ximena , Figueroa-Corona Laura , Martínez-Villegas Jorge Arturo , Soriano Diana , Gamboa-deBuen Alicia
Published: May 2021

Germination represents the culmination of the seed developmental program and is affected by the conditions prevailing during seed maturation in the mother plant. During maturation, the dormancy condition and tolerance to dehydration are established. These characteristics are modulated by the environment to which they are subjected, having an important impact on wild species. In this work, a review was made of the molecular bases of the maturation, the processes of dormancy imposition and loss, as well as the germination process in different wild species with different life histories, and from diverse habitats. It is also specified which of these species present a certain type of management. The impact that the domestication process has had on certain characteristics of the seed is discussed, as well as the importance of determining physiological stages based on morphological characteristics, to face the complexities of the study of these species and preserve their genetic diversity and physiological responses.
Genome-Wide Association Mapping of Salinity Tolerance at the Seedling Stage in a Panel of Vietnamese Landraces Reveals New Valuable QTLs for Salinity Stress Tolerance Breeding in Rice
Authors: Le Thao Duc , Gathignol Floran , Vu Huong Thi , Nguyen Khanh Le , Tran Linh Hien , Vu Hien Thi Thu , Dinh Tu Xuan , Lazennec Françoise , Pham Xuan Hoi , Véry Anne-Aliénor , Gantet Pascal , Hoang Giang Thi
Published: May 2021

Rice tolerance to salinity stress involves diverse and complementary mechanisms, such as the regulation of genome expression, activation of specific ion-transport systems to manage excess sodium at the cell or plant level, and anatomical changes that avoid sodium penetration into the inner tissues of the plant. These complementary mechanisms can act synergistically to improve salinity tolerance in the plant, which is then interesting in breeding programs to pyramidize complementary QTLs (quantitative trait loci), to improve salinity stress tolerance of the plant at different developmental stages and in different environments. This approach presupposes the identification of salinity tolerance QTLs associated with different mechanisms involved in salinity tolerance, which requires the greatest possible genetic diversity to be explored. To contribute to this goal, we screened an original panel of 179 Vietnamese rice landraces genotyped with 21,623 SNP markers for salinity stress tolerance under 100 mM NaCl treatment, at the seedling stage, with the aim of identifying new QTLs involved in the salinity stress tolerance via a genome-wide association study (GWAS). Nine salinity tolerance-related traits, including the salt injury score, chlorophyll and water content, and K+ and Na+ contents were measured in leaves. GWAS analysis allowed the identification of 26 QTLs. Interestingly, ten of them were associated with several different traits, which indicates that these QTLs act pleiotropically to control the different levels of plant responses to salinity stress. Twenty-one identified QTLs colocalized with known QTLs. Several genes within these QTLs have functions related to salinity stress tolerance and are mainly involved in gene regulation, signal transduction or hormone signaling. Our study provides promising QTLs for breeding programs to enhance salinity tolerance and identifies candidate genes that should be further functionally studied to better understand salinity tolerance mechanisms in rice.
Assessment of Planting Method and Deficit Irrigation Impacts on Physio-Morphology, Grain Yield and Water Use Efficiency of Maize (Zea mays L.) on Vertisols of Semi-Arid Tropics
Authors: Halli Hanamant M. , Angadi Sanganabasappa , Kumar Aravind , Govindasamy Prabhu , Madar Raghavendra , Baskar V David Chella , Elansary Hosam O. , Tamam Nissren , Abdelbacki Ashraf M. M. , Abdelmohsen Shaimaa A. M.
Published: May 2021

Agriculture in a water-limited environment is critically important for today and for the future. This research evaluates the impact of deficit irrigation in different planting methods on the physio-morphological traits, grain yield and WUE of maize (Zea mays L.). The experiment was carried out in 2015 and 2016, consisting of three planting methods (i.e., BBF, SNF, and DWF) and four irrigation levels (i.e., I10D: irrigation once in ten days, I40: irrigation at 40% DASM, I50: irrigation at 50% DASM, and I60: irrigation at 60% DASM). The results reveal that varying degrees of water stress due to planting methods and irrigation levels greatly influenced the maize physio-morphological traits and yield attributes. The combined effect of DWF + I50 benefited the maize in terms of higher leaf area, RWC, SPAD values, CGR, and LAD, followed by the SNF method at 60 DAS. As a result, DWF + I50 and SNF + I50 had higher 100 grain weight (30.5 to 31.8 g), cob weight (181.4 to 189.6 g cob−1) and grain yield (35.3% to 36.4%) compared to other treatments. However, the reduction in the number of irrigations (24.0%) under SNF + I50 resulted in a 34% water saving. Thus, under a water-limited situation in semi-arid tropics, the practice of the SNF method + I50 could be an alternative way to explore the physio-morphological benefits in maize.
In Response to Abiotic Stress, DNA Methylation Confers EpiGenetic Changes in Plants
Authors: Akhter Zahida , Bi Zhenzhen , Ali Kazim , Sun Chao , Fiaz Sajid , Haider Fasih Ullah , Bai Jiangping
Published: May 2021

Epigenetics involves the heritable changes in patterns of gene expression determined by developmental and abiotic stresses, i.e., drought, cold, salinity, trace metals, and heat. Gene expression is driven by changes in DNA bases, histone proteins, the biogenesis of ncRNA, and changes in the nucleotide sequence. To cope with abiotic stresses, plants adopt certain changes driven by a sophisticated biological system. DNA methylation is a primary mechanism for epigenetic variation, which can induce phenotypic alterations in plants under stress. Some of the stress-driven changes in plants are temporary, while some modifications may be stable and inheritable to the next generations to allow them to cope with such extreme stress challenges in the future. In this review, we discuss the pivotal role of epigenetically developed phenotypic characteristics in plants as an evolutionary process participating in adaptation and tolerance responses to abiotic and biotic stresses that alter their growth and development. We emphasize the molecular process underlying changes in DNA methylation, differential variation for different species, the roles of non-coding RNAs in epigenetic modification, techniques for studying DNA methylation, and its role in crop improvement in tolerance to abiotic stress (drought, salinity, and heat). We summarize DNA methylation as a significant future research priority for tailoring crops according to various challenging environmental issues.
Morpho-Physiological Testing of NaCl Sensitivity of Tobacco Plants Overexpressing Choline Oxidase Gene
Authors: Raldugina Galina N. , Evsukov Sergey V. , Bogoutdinova Liliya R. , Gulevich Alexander A. , Baranova Ekaterina N.
Published: May 2021

In this study the transgenic lines (TLs) of tobacco (Nicotianatabacum L.), which overexpress the heterologous gene encoding the bacterial enzyme choline oxidase were evaluated. The goal of our work is to study the effect of choline oxidase gene expression on the sensitivity of plant tissues to the action of NaCl. The regenerative capacity, rhizogenesis, the amount of photosynthetic pigments and osmotically active compounds (proline and glycine betaine) were assessed by in vitro cell culture methods using biochemical and morphological parameters. Transgenic lines with confirmed expression were characterized by high regeneration capacity from callus in the presence of 200 mmol NaCl, partial retention of viability at 400 mmol NaCl. These data correlated with the implicit response of regenerants and whole plants to the harmful effects of salinity. They turned out to be less sensitive to the presence of 200 mmol NaCl in the cultivation medium, in contrast to the WT plants.