bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of Body Weight Variability with Adverse Cardiovascular Outcomes in Patients with Pre-Dialysis Chronic Kidney Disease
Authors: Suh Sang Heon , Oh Tae Ryom , Choi Hong Sang , Kim Chang Seong , Bae Eun Hui , Park Sue K. , Kim Yong-Soo , Kim Yeong Hoon , Choi Kyu Hun , Oh Kook-Hwan , Ma Seong Kwon , Kim Soo Wan ,   on behalf of the KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD) Investigators
Published: September 2021

To investigate the association of body weight variability (BWV) with adverse cardiovascular (CV) outcomes in patient with pre-dialysis chronic kidney disease (CKD), a total of 1867 participants with pre-dialysis CKD from Korean Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD) were analyzed. BWV was defined as the average absolute difference between successive values. The primary outcome was a composite of non-fatal CV events and all-cause mortality. Secondary outcomes were fatal and non-fatal CV events and all-cause mortality. High BWV was associated with increased risk of the composite outcome (adjusted hazard ratio (HR) 1.745, 95% confidence interval (CI) 1.065 to 2.847) as well as fatal and non-fatal CV events (adjusted HR 1.845, 95% CI 1.136 to 2.996) and all-cause mortality (adjusted HR 1.861, 95% CI 1.101 to 3.145). High BWV was associated with increased risk of fatal and non-fatal CV events, even in subjects without significant body weight gain or loss during follow-up periods (adjusted HR 2.755, 95% CI 1.114 to 6.813). In conclusion, high BWV is associated with adverse CV outcomes in patients with pre-dialysis CKD.
Inhibitory Effect of Tangeretin and Cardamonin on Human Intestinal SGLT1 Activity In Vitro and Blood Glucose Levels in Mice In Vivo
Authors: Satsu Hideo , Shibata Ryosuke , Suzuki Hiroto , Kimura Shimon , Shimizu Makoto
Published: September 2021

Rapid postprandial blood glucose elevation can cause lifestyle-related diseases, such as type II diabetes. The absorption of food-derived glucose is primarily mediated by sodium/glucose cotransporter 1 (SGLT1). Moderate SGLT1 inhibition can help attenuate postprandial blood glucose elevation and prevent lifestyle-related diseases. In this study, we established a CHO cell line stably expressing human SGLT1 and examined the effects of phytochemicals on SGLT1 activity. Among the 50 phytochemicals assessed, tangeretin and cardamonin inhibited SGLT1 activity. Tangeretin and cardamonin did not affect the uptake of L-leucine, L-glutamate, and glycyl-sarcosine. Tangeretin, but not cardamonin, inhibited fructose uptake, suggesting that the inhibitory effect of tangeretin was specific to the monosaccharide transporter, whereas that of cardamonin was specific to SGLT1. Kinetic analysis suggested that the suppression of SGLT1 activity by tangeretin was associated with a reduction in Vmax and an increase in Km, whereas suppression by cardamonin was associated with a reduction in Vmax and no change in Km. Oral glucose tolerance tests in mice showed that tangeretin and cardamonin significantly suppressed the rapid increase in blood glucose levels. In conclusion, tangeretin and cardamonin were shown to inhibit SGLT1 activity in vitro and lower blood glucose level in vivo.
The Controversial Role of Adiponectin in Appetite Regulation of Animals
Authors: Tang Ni , Zhang Xin , Chen Defang , Li Zhiqiong
Published: September 2021

Eating disorders and obesity are important health problems with a widespread global epidemic. Adiponectin (AdipoQ), the most abundant adipokine in the plasma, plays important roles in the regulation of energy homeostasis, glucose metabolism and lipid metabolism. Plasma adiponectin concentration is negatively associated with obesity and binge eating disorder. There is a growing interest in the appetite regulation function of adiponectin. However, the effect of AdipoQ on feeding behavior is controversial and closely related to nutritional status and food composition. In this review, we summarize the literatures about the discovery, structure, tissue distribution, receptors and regulation of nutritional status, and focus on the biological function of adiponectin in the regulation of food intake in the central and peripheral system.
Standardised Outcome Reporting for the Nutrition Management of Complex Chronic Disease: A Rapid Review
Authors: Sandhu Savita A , Angel Chloe A , Campbell Katrina L , Hickman Ingrid J , MacLaughlin Helen L
Published: September 2021

Individuals with coexisting chronic diseases or with complex chronic disease are among the most challenging and costly patients to treat, placing a growing demand on healthcare systems. Recommending effective treatments, including nutrition interventions, relies on standardised outcome reporting from randomised controlled trials (RCTs) to enable data synthesis. This rapid review sought to determine how the scope and consistency of the outcomes reported by RCTs investigating nutrition interventions for the management of complex chronic disease compared to what is recommended by the core outcome sets (COS) for individual disease states. Peer-reviewed RCTs published between January 2010 and July 2020 were systematically sourced from PubMed, CINAHL and Embase, and COS were sourced from the International Consortium for Health Outcomes Measurements (ICHOM) and the Core Outcome Measures in Effectiveness Trials (COMET) database. A total of 45 RCTs (43 studies) and 7 COS were identified. Outcomes were extracted from both the RCTs and COS and were organised using COMET Taxonomy Core Areas. A total of 66 outcomes and 439 outcome measures were reported by the RCTs. The RCTs demonstrated extensive outcome heterogeneity, with only five outcomes (5/66, 8%) being reported with relative consistency (cited by ≥50% of publications). Furthermore, the scope of the outcomes reported by studies was limited, with a notable paucity of patient-reported outcomes. Poor agreement (25%) was observed between the outcomes reported in the RCTs and those recommended by the COS. This review urges greater uptake of the existing COS and the development of a COS for complex chronic disease to be considered so that evidence can be better synthesised regarding effective nutrition interventions.
Supper Timing and Cardiovascular Mortality: The Japan Collaborative Cohort Study
Authors: Tang Jingyun , Dong Jia-Yi , Eshak Ehab S. , Cui Renzhe , Shirai Kokoro , Liu Keyang , Sakaniwa Ryoto , Tamakoshi Akiko , Iso Hiroyasu ,   on behalf of the JACC Study Group
Published: September 2021

Evidence on the role of supper timing in the development of cardiovascular disease (CVD) is limited. In this study, we examined the associations between supper timing and risks of mortality from stroke, coronary heart disease (CHD), and total CVD. A total of 28,625 males and 43,213 females, aged 40 to 79 years, free from CVD and cancers at baseline were involved in this study. Participants were divided into three groups: the early supper group (before 8:00 p.m.), the irregular supper group (time irregular), and the late supper group (after 8:00 p.m.). Cox proportional hazards regression models were used to calculate hazard ratios (HRs) for stroke, CHD, and total CVD according to the supper time groups. During the 19-year follow-up, we identified 4706 deaths from total CVD. Compared with the early supper group, the multivariable HR of hemorrhagic stroke mortality for the irregular supper group was 1.44 (95% confidence interval [CI]: 1.05–1.97). There was no significant association between supper timing and the risk of mortality from other types of stroke, CHD, and CVD. We found that adopting an irregular supper timing compared with having dinner before 8:00 p.m. was associated with an increased risk of hemorrhagic stroke mortality.
Ultra-Processed Foods and Nutritional Dietary Profile: A Meta-Analysis of Nationally Representative Samples
Authors: Martini Daniela , Godos Justyna , Bonaccio Marialaura , Vitaglione Paola , Grosso Giuseppe
Published: September 2021

Excessive consumption of ultra-processed foods (UPFs), as described by the NOVA classification system, represents a potential threat to human health. The nutritional composition of UPFs may explain their observed adverse effects. The present study aimed to provide a quantitative meta-analysis of nationally representative surveys on the consumption of UPFs and the dietary/nutrient composition of respondents’ diets. A systematic search for relevant studies published prior to July 2021 was conducted via electronic databases. The studies that provided the dietary/nutrient composition of foods categorized according to the NOVA classification system were selected. The association between UPFs and other dietary variables was modelled using ordinary least squares linear regression based on aggregated data extracted from the selected articles. Consumption of UPFs represented up to 80% of total caloric intake in the US and Canada, with confectionery and sugar-sweetened beverages being the most consumed items. When considered in relation to other food groups, an inverse linear relation between UPFs and less-processed foods was evident. Increased UPF intake correlated with an increase in free sugars, total fats, and saturated fats, as well as a decrease in fiber, protein, potassium, zinc, and magnesium, and vitamins A, C, D, E, B12, and niacin. In conclusion, the data indicate that increased UPF consumption negatively affects the nutritional quality of diets.
Web-Based Personalized Nutrition System for Delivering Dietary Feedback Based on Behavior Change Techniques: Development and Pilot Study among Dietitians
Authors: Murakami Kentaro , Shinozaki Nana , Masayasu Shizuko , Livingstone M. Barbara E.
Published: September 2021

Given the complex and varied nature of individual characteristics influencing dietary behaviors, personalized dietary advice may be more effective than generalized “one-size-fits-all” advice. In this paper, we describe a web-based personalized nutrition system for improving the quality of overall diet in the general adult population. The development process included identification of appropriate behavior change techniques, modification of dietary assessment method (Meal-based Diet History Questionnaire; MDHQ), selection of dietary components, and a personalized dietary feedback tool. A pilot study was conducted online among 255 dietitians. Each completed the MDHQ, received his/her own dietary feedback report, and evaluated the relevance of the report based on 12 questions using a 5-point Likert scale from “totally disagree” (score 1) to “totally agree” (score 5). The mean value of overall acceptability score of dietary feedback report was 4.2. The acceptability score was, on average, higher in plausible energy reporters (compared with implausible energy reporters), participants who printed out the report (compared with those who did not), and those spending ≥20 min to read the report (compared with those spending <20 min). This is the first attempt to develop a web-based personalized nutrition system in Japan, where dietitians were broadly supportive of the dietary feedback report.
Dysmagnesemia Is the Most Common Disturbance of the Calcium–Magnesium–Phosphorous Balance among Older Hospitalized People in Warsaw
Authors: Malinowska Justyna , Małecka-Giełdowska Milena , Ciepiela Olga
Published: September 2021

The elderly are at great risk of developing life-threatening disturbances in calcium–magnesium–phosphate homeostasis because of comorbidities, long-term medication use, and dietary deficiencies, but it is still not known how often they occur in this group of patients. This study aimed to assess the prevalence of these disturbances in a group of hospitalized patients over 65 years of age according to age and sex. The study was conducted between January 2018 and September 2020 at the Central Clinical Hospital in Warsaw. A total of 66,450 calcium, magnesium, phosphate, and vitamin D concentration results were included in the analysis. Dysmagnesemia was present in 33% of the calcium results, dyscalcemia, dysphosphatemia, and dysvitaminosis D—in 23.5%, 26%, and 70% of the results, respectively. The magnesium concentration was found to be age-dependent, and older people were found to be at higher risk of developing abnormal magnesium concentrations (p < 0.001). Sex influenced the occurrence of abnormal magnesium (p < 0.001), vitamin D (p < 0.001), and calcium (p < 0.00001) concentrations, with hypercalcemia and hypervitaminosis D disorders being significantly more common in women (p < 0.0001). In conclusion, disorders of the calcium–magnesium–phosphate metabolism are common in hospitalized patients over 65 years of age, and the concentrations of these substances should be routinely monitored in this group.
Energy Requirement for Elderly CKD Patients
Authors: D’Alessandro Claudia , Giannese Domenico , Avino Monica , Cupisti Adamasco
Published: September 2021

The correct management of energy intake is crucial in CKD (chronic kidney disease) patients to limit the risk of protein energy wasting especially during low-protein regimes, but also to prevent overweight/obesity. The aim of this study was to assess the energy requirement of older CKD patients using objective measurements. This cross-sectional study enrolled 67 patients (aged 60–86 years) with CKD stages 3–5 not on dialysis, all of whom were metabolically and nutritionally stable. All patients underwent indirect calorimetry and measurement of daily physical activity level expressed by the average daily Metabolic Equivalent Task, using an accelerometer, in order to measure total energy expenditure (mTEE). Estimated TEE (eTEE) was derived from predictive equations for resting energy expenditure and physical activity levels coefficients. The mTEE were lower than eTEE-based on Harris–Benedict or Schofield or Mifflin equations (1689 ± 523 vs. 2320 ± 434 or 2357 ± 410 or 2237 ± 375 Kcal, p < 0.001, respectively). On average mTEE was 36.5% lower than eTEE. When eTEE was recalculated using ideal body weight the gap between mTEE and eTEE was reduced to 26.3%. A high prevalence of a sedentary lifestyle and reduced physical capabilities were also detected. In conclusion, our data support the energy intake of 25–35 Kcal/Kg/d recently proposed by the NKF-KDOQI (National Kidney Foundation-Kidney Disease Improving Quality Initiative) guidelines on nutritional treatment of CKD, which seem to be more adequate and applicable than that of previous guidelines (30–35 Kcal/Kg/d) in elderly stable CKD patients with a sedentary lifestyle. According to our findings we believe that an energy intake even lower than 25 Kcal/Kg/d may be adequate in metabolically stable, elderly CKD patients with a sedentary lifestyle.
Molecular Basis of IgE-Mediated Shrimp Allergy and Heat Desensitization
Authors: Zhang PeiAo , Gao Jihui , Che Huilian , Xue Wentong , Yang Dong
Published: September 2021

Crustacean allergy, especially to shrimp, is the most predominant cause of seafood allergy. However, due to the high flexibility of immunoglobulin E (IgE), its three-dimensional structure remains unsolved, and the molecular mechanism of shrimp allergen recognition is unknown. Here a chimeric IgE was built in silico, and its variable region in the light chain was replaced with sequences derived from shrimp tropomyosin (TM)-allergic patients. A variety of allergenic peptides from the Chinese shrimp TM were built, treated with heating, and subjected to IgE binding in silico. Amino acid analysis shows that the amino acid residue conservation in shrimp TM contributes to eliciting an IgE-mediated immune response. In the shrimp-allergic IgE, Glu98 in the light chain and other critical residues that recognize allergens from shrimp are implicated in the molecular basis of IgE-mediated shrimp allergy. Heat treatment could alter the conformations of TM allergenic peptides, impact their intramolecular hydrogen bonding, and subsequently decrease the binding between these peptides and IgE. We found Glu98 as the characteristic amino acid residue in the light chain of IgE to recognize general shrimp-allergic sequences, and heat-induced conformational change generally desensitizes shrimp allergens.
The Role of Carrageenan in Inflammatory Bowel Diseases and Allergic Reactions: Where Do We Stand?
Authors: Borsani Barbara , De Santis Raffaella , Perico Veronica , Penagini Francesca , Pendezza Erica , Dilillo Dario , Bosetti Alessandra , Zuccotti Gian Vincenzo , D’Auria Enza
Published: September 2021

Carrageenan (CGN) is a high molecular weight polysaccharide extracted from red seaweeds, composed of D-galactose residues linked in β-1,4 and α-1,3 galactose-galactose bond, widely used as a food additive in processed foods for its properties as a thickener, gelling agent, emulsifier, and stabilizer. In recent years, with the spread of the Western diet (WD), its consumption has increased. Nonetheless, there is a debate on its safety. CGN is extensively used as an inflammatory and adjuvant agent in vitro and in animal experimental models for the investigation of immune processes or to assess the activity of anti-inflammatory drugs. CGN can activate the innate immune pathways of inflammation, alter the gut microbiota composition and the thickness of the mucus barrier. Clinical evidence suggests that CGN is involved in the pathogenesis and clinical management of inflammatory bowel diseases (IBD), indeed food-exclusion diets can be an effective therapy for disease remission. Moreover, specific IgE to the oligosaccharide α-Gal has been associated with allergic reactions commonly referred to as the “α-Gal syndrome”. This review aims to discuss the role of carrageenan in inflammatory bowel diseases and allergic reactions following the current evidence. Furthermore, as no definitive data are available on the safety and the effects of CGN, we suggest gaps to be filled and advise to limit the human exposure to CGN by reducing the consumption of ultra-processed foods.
Perceived Parental Attitudes Are Indirectly Associated with Consumption of Junk Foods and Sugar-Sweetened Beverages among Chinese Adolescents through Home Food Environment and Autonomous Motivation: A Path Analysis
Authors: Qiu Nan , Moore Justin B. , Wang Yechuang , Fu Jialin , Ding Kai , Li Rui
Published: September 2021

This study aimed to use path analysis to determine the association between perceived parental attitudes toward restricting junk food (JF)/sugar-sweetened beverage (SSB) intake and JF/SSB consumption among Chinese adolescents, and whether JF/SSB availability in the home environment and autonomous motivation of adolescents mediated the association. A cross-sectional survey was conducted using questionnaires adapted from the Family Life, Activity, Sun, Health, and Eating (FLASHE) Study to collect data on 3819 participants with an average age of 14.7 years (SD = 1.7). Spearman correlations and path analysis were performed. It was found that perceived parental attitudes were not directly associated with adolescents’ JF/SSB consumption frequency, but indirectly related to them through JF/SSB availability in the home environment and autonomous motivation of adolescents. When parents held a less positive attitude toward JF/SSB consumption and kept less JFs/SSBs at home, youth displayed more autonomous motivation for restricting JF/SSB intake and consumed fewer JFs/SSBs.
Microarray Analysis of Paramylon, Isolated from Euglena Gracilis EOD-1, and Its Effects on Lipid Metabolism in the Ileum and Liver in Diet-Induced Obese Mice
Authors: Aoe Seiichiro , Yamanaka Chiemi , Mio Kento
Published: September 2021

We previously showed that supplementation of a high fat diet with paramylon (PM) reduces the postprandial glucose rise, serum total and LDL cholesterol levels, and abdominal fat accumulation in mice. The purpose of this study was to explore the underlying mechanism of PM using microarray analysis. Male mice (C57BL/BL strain) were fed an experimental diet (50% fat energy) containing 5% PM isolated from Euglena gracilis EOD-1 for 12 weeks. After confirming that PM had an improving effect on lipid metabolism, we assessed ileal and hepatic mRNA expression using DNA microarray and subsequent analysis by gene ontology (GO) classification and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. The results suggested that dietary supplementation with PM resulted in decreased abdominal fat accumulation and serum LDL cholesterol concentrations via suppression of the digestion and absorption pathway in the ileum and activation of the hepatic PPAR signaling pathway. Postprandial glucose rise was reduced in mice fed PM, whereas changes in the glucose metabolism pathway were not detected in GO classification and KEGG pathway analysis. PM intake might enhance serum secretory immunoglobulin A concentrations via promotion of the immunoglobulin production pathway in the ileum.
Effects of Delayed-Release Olive Oil and Hydrolyzed Pine Nut Oil on Glucose Tolerance, Incretin Secretion and Appetite in Humans
Authors: Sørensen Karina V. , Kaspersen Mads H. , Ekberg Jeppe H. , Bauer-Brandl Annette , Ulven Trond , Højlund Kurt
Published: September 2021

Background: To investigate the potential synergistic effects of olive oil releasing 2-oleoylglycerol and hydrolyzed pine nut oil containing 20% pinolenic acid on GLP-1 secretion, glucose tolerance, insulin secretion and appetite in healthy individuals, when delivered to the small intestine as potential agonists of GPR119, FFA1 and FFA4. Methods: Nine overweight/obese individuals completed three 6-h oral glucose tolerance tests (OGTTs) in a crossover design. At −30 min, participants consumed either: no oil, 6 g of hydrolyzed pine nut oil (PNO-FFA), or a combination of 3 g hydrolyzed pine nut oil and 3 g olive oil (PNO-OO) in delayed-release capsules. Repeated measures of glucose, insulin, C-peptide, GLP-1, GIP, ghrelin, subjective appetite and gastrointestinal tolerability were done. Results: PNO-FFA augmented GLP-1 secretion from 0–360 min compared to no oil and PNO-OO (p < 0.01). GIP secretion was increased from 240–360 min after both PNO-FFA and PNO-OO versus no oil (p < 0.01). Both oil treatments suppressed subjective appetite by reducing hunger and prospective food consumption and increasing satiety (p < 0.05). Conclusions: In support of previous findings, 6 g of delayed-release hydrolyzed pine nut oil enhanced postprandial GLP-1 secretion and reduced appetite. However, no synergistic effect of combining hydrolyzed pine nut oil and olive oil on GLP-1 secretion was observed. These results need further evaluation in long-term studies including effects on bodyweight and insulin sensitivity.
Which Milk during the Second Year of Life: A Personalized Choice for a Healthy Future?
Authors: Verduci Elvira , Di Profio Elisabetta , Corsello Antonio , Scatigno Lorenzo , Fiore Giulia , Bosetti Alessandra , Zuccotti Gian Vincenzo
Published: September 2021

Nutrition in early life is a crucial element to provide all essential substrates for growth. Although this statement may appear obvious, several studies have shown how the intake of micro and macronutrients in toddlers differs a lot from the recommendations of scientific societies. Protein intake often exceeds the recommended amount, while the intake of iron and zinc is frequently insufficient, as well as Vitamin D. Nutritional errors in the first years of life can negatively impact the health of the child in the long term. To date, no clear evidence on which milk is suggested during the second year of life is yet to be established. In this study, we compare the nutrient profiles of cow’s milk and specific formulas as well as nutritional risks in toddlers linked to growth and childhood obesity development. The purpose of this review is to resume the latest clinical studies on toddlers fed with cow’s milk or young children formula (YCF), and the potential risks or benefits in the short and long term.
The Diagnosis, Treatment, Surveillance and Control of Cystic Echinococcosis in the Province of Rio Negro: The “One-Health” Model
Authors: Mujica Guillermo , Uchiumi Leonardo , Araya Daniel , Salvitti Juan Carlos , Labanchi Jose Luis , Sobrino Mariano , Herrero Eduardo , Panomarenko Oscar , Blanco Patricia , Talmon Gabriel , Tissot Hebe , Grizmado Claudia , Arezo Marcos , Seleiman Marcos , Mercapide Carlos Hugo , Larrieu Edmundo
Published: September 2021

Cystic Echinococcosis (CE) is an endemo-epidemic disease in the Rio Negro Province, República Argentina. Due to the number of cases, the length of hospital stays after surgery and its associated mortality, it is a serious public health problem that generates high costs for the health system. Oriented towards its control, primary prevention activities have been carried out since 1980, based on the deworming of dogs and the vaccination of lambs; secondary prevention has consisted in the actively search for cases through serological or ultrasonographic screening; and tertiary prevention has been based on timely treatment, either by surgery or by medical treatment with albendazole. All these prevention activities have been carried out under the concept and strategies of the “One Health” model, through both inter-institutional and interdisciplinary work, as well as with the support, commitment and critical participation of the community. As a result, an important drop has been observed in the prevalence of CE in humans and in its lethality (0.5% in 1997–2020, no deaths in the last two years); moreover, an important decrease has been observed in costs to the health system, due to the reduction of hospitalizations and the number of surgeries.
Are the Organoid Models an Invaluable Contribution to ZIKA Virus Research?
Authors: Marrazzo Pasquale , Cricca Monica , Nastasi Claudia
Published: September 2021

In order to prevent new pathogen outbreaks and avoid possible new global health threats, it is important to study the mechanisms of microbial pathogenesis, screen new antiviral agents and test new vaccines using the best methods. In the last decade, organoids have provided a groundbreaking opportunity for modeling pathogen infections in human brains, including Zika virus (ZIKV) infection. ZIKV is a member of the Flavivirus genus, and it is recognized as an emerging infectious agent and a serious threat to global health. Organoids are 3D complex cellular models that offer an in-scale organ that is physiologically alike to the original one, useful for exploring the mechanisms behind pathogens infection; additionally, organoids integrate data generated in vitro with traditional tools and often support those obtained in vivo with animal model. In this mini-review the value of organoids for ZIKV research is examined and sustained by the most recent literature. Within a 3D viewpoint, tissue engineered models are proposed as future biological systems to help in deciphering pathogenic processes and evaluate preventive and therapeutic strategies against ZIKV. The next steps in this field constitute a challenge that may protect people and future generations from severe brain defects.
Pharmacokinetic/Pharmacodynamic Modeling of Spiramycin against Mycoplasma synoviae in Chickens
Authors: Elazab Sara T. , Elshater Nahla S. , Hashem Yousreya H. , Al-Atfeehy Nayera M. , Lee Eon-Bee , Park Seung-Chun , Hsu Walter H.
Published: September 2021

This research aimed to assess the pharmacokinetics/pharmacodynamics (PK/PD) and tissue residues of spiramycin in chickens. The PK of spiramycin were determined in 12 chickens using a parallel study design in which each group of chickens (n = 6) received a single dose of spiramycin at 17 mg/kg intravenously (IV) or orally. Plasma samples were collected at assigned times for up to 48 h to measure spiramycin concentrations. Additionally, a tissue depletion study was performed in 42 chickens receiving spiramycin at 17 mg/kg/day orally for 7 days. The area under the plasma concentration–time curve values were 29.94 ± 4.74 and 23.11 ± 1.83 µg*h/mL after IV and oral administrations, respectively. The oral bioavailability was 77.18%. The computed withdrawal periods of spiramycin were 11, 10, and 7 days for liver, muscle, and skin and fat, respectively. The minimum inhibitory concentration for spiramycin against Mycoplasma synoviae (M. synoviae) strain 1853 was 0.0625 µg/mL. Using the PK/PD integration, the appropriate oral dose of spiramycin against M. synoviae was estimated to be 15.6 mg/kg. Thus, we recommend an oral dose of 15.6 mg spiramycin/kg against M. synoviae in chickens and a withdrawal period of 11 days following oral treatment with 17 mg spiramycin/kg/day for 7 days.
Selection of Endophytic Beauveria bassiana as a Dual Biocontrol Agent of Tomato Pathogens and Pests
Authors: Sinno Martina , Ranesi Marta , Di Lelio Ilaria , Iacomino Giuseppina , Becchimanzi Andrea , Barra Eleonora , Molisso Donata , Pennacchio Francesco , Digilio Maria Cristina , Vitale Stefania , Turrà David , Harizanova Vili , Lorito Matteo , Woo Sheridan Lois
Published: September 2021

Endophytic fungi (EF) can enhance both plant growth and defense barriers against pests and pathogens, contributing to the reduction of chemical pesticides and fertilizers use in agriculture. Beauveria bassiana is an entomopathogenic fungus showing endophytism in several crops, often associated with a good capacity to limit the development of pests and disease agents. However, the diversity of the protective efficacy and plant response to different strains can be remarkable and needs to be carefully assessed for the successful and predictable use of these beneficial microorganisms. This study aims to select B. bassiana strains able to colonize tomato plants as endophytes as well as to control two important disease agents, Botrytis cinerea and Alternaria alternata, and the pest aphid, Macrosiphum euphorbiae. Nine wild-type isolates and one commercial strain were screened for endophytism, then further characterized for plant-growth promotion plus inhibition of disease development and pest infestation. Four isolates proved to have a good control activity against the biotic stressors tested, but only Bb716 was also able to promote plant growth. This work provides a simple workflow for the selection of beneficial EF, paving the way towards more effective use of B. bassiana in Integrate Pest Management (IPM) of tomato.
Morphology, Phylogeny and Pathogenicity of Colletotrichum menglaense sp. nov., Isolated from Air in China
Authors: Qiao Min , Li Jie , Fang Lin-lin , Li Jian-ying , Yu Ze-fen
Published: September 2021

A new species, Colletotrichum menglaense, isolated from air in Mengla, Xishuangbanna, Yunnan Province, China, was characterized and described combining morphological characteristics and multigene phylogenetic analysis. Morphologically, it is characterized by oblong, sometimes slightly constricted, micro-guttulate conidia and simple obovoid to ellipsoidal appressoria. Phylogenetic analysis of the ITS, ACT, CHS, and GAPDH sequences showed that C. menglaense belongs to the C. gloeosporioides complex. The pathogenicity of C. menglaense on fruits of several crop plants, including strawberry, orange, grape, tomato, and blueberry, was tested and confirmed by the re-isolation of C. menglaense.
Genetic Variability and Evidence of a New Subgroup in Watermelon Mosaic Virus Isolates
Authors: Abdalla Osama A. , Ali Akhtar
Published: September 2021

Watermelon mosaic virus (WMV) is one of the important Potyviruses that infect cucurbits worldwide. To better understand the population structure of WMV in the United States (U.S.), 57 isolates were collected from cucurbit fields located in nine southern states. The complete coat protein gene of all WMV isolates was cloned, sequenced and compared with 89 reported WMV isolates. The nucleotide and amino acid sequence identities among the U.S. WMV isolates ranged from 88.9 to 99.7% and from 91.5 to 100%, respectively. Phylogenetic analysis revealed that all the U.S. WMV isolates irrespective of their geographic origin or hosts belonged to Group 3. However, the fifty-seven isolates made three clusters in G3, where two clusters were similar to previously reported subgroups EM1 and EM2, and the third cluster, containing nine WMV isolates, formed a distinct subgroup named EM5 in this study. The ratio of non-synonymous to synonymous nucleotide substitution was low indicating the occurrence of negative purifying selection in the CP gene of WMV. Phylogenetic analysis of selected 37 complete genome sequences of WMV isolates also supported the above major grouping. Recombination analysis in the CP genes confirmed various recombinant events, indicating that purifying selection and recombination are the two dominant forces for the evolution of WMV isolates in the U.S.
Occurrence and Genetic Correlations of Yersinia spp. Isolated from Commensal Rodents in Northeastern Poland
Authors: Platt-Samoraj Aleksandra , Kończyk-Kmiecik Klaudia , Bakuła Tadeusz
Published: September 2021

Rodents can be a potential Yersinia spp. vector responsible for farm facilities contamination. The aim of the study was to determine the prevalence of Yersinia spp. in commensal rodents found in the farms and fodder factory areas to characterize the obtained isolates and epidemiological risk. Intestinal samples were subjected to bacteriological, bioserotype, and PCR examination for virulence markers ail, ystA, ystB, and inv presence. Yersinia spp. was isolated from 43 out of 244 (17.6%) rodents (Apodemus agrarius n = 132, Mus musculus n = 102, Apodemus sylvaticus n = 8, Rattus norvegicus n = 2). Y. enterocolitica was isolated from 41 rodents (16.8%), and from one Y. pseudotuberculosis and one Y. kristensenii. In three cases, two Y. enterocolitica isolates were obtained from one rodent. All Y. enetrocolitica contained ystB and belonged to biotype 1A, considered as potentially pathogenic. One isolate additionally had the ail gene typical for pathogenic strains. The sequence analysis of the ystB, ail, and inv fragments showed a high similarity to those from clinical cases. The current study revealed a high prevalence of Y. enetrocolitica among commensal rodents, but the classification of all of Y. enterocolitica isolates into biotype 1A and the sporadic isolation of Y. pseudotuberculosis do not indicate a high epidemiological risk.
Prevalence and Intensity of Cardicola spp. Infection in Ranched Southern Bluefin Tuna and a Comparison of Diagnostic Methods
Authors: Power Cecilia , Evenden Shannon , Rough Kirsten , Webber Claire , Widdicombe Maree , Nowak Barbara F. , Bott Nathan J.
Published: September 2021

The parasitic blood flukes Cardicola forsteri and C. orientalis are an ongoing health concern for Southern Bluefin Tuna Thunnus maccoyii (SBT) ranched in Australia. In this study we compared the effect of treatment, company, and ranching year on blood fluke infections in ranched SBT. SBT were sampled during the 2018 and 2019 ranching seasons from praziquantel (PZQ) treated pontoons and untreated pontoons managed by two companies. Severity of infection was diagnosed by several criteria including adult fluke counts from hearts, egg counts from gill filaments and the use of specific quantitative polymerase chain reaction (qPCR) for detection of C. forsteri and C. orientalis ITS-2 DNA in SBT hearts and gills. PZQ treatment remains highly effective against C. forsteri infection. Prevalence and intensity of Cardicola spp. infection was lower in 2019 than 2018 for Company A in treated pontoons at week 12 and week 17 of ranching, and lower for Company A than Company B in untreated pontoons at month 5 of ranching. Results indicate re-infection may be less likely in the environment near Company A pontoons, and consistent years of treatment may have lowered the parasite load in the environment. qPCR demonstrated higher sensitivity when comparing diagnostic methods for C. forsteri in heart, and higher specificity when comparing diagnostic methods for Cardicola spp. in gills. Continuing to monitor blood fluke infections in ranched SBT can help to detect changes in drug efficacy over time and help industry to develop a best practice for treatment.
Uncommon Clinical Presentations of Sporotrichosis: A Two-Case Report
Authors: Martínez-Herrera Erick , Arenas Roberto , Hernández-Castro Rigoberto , Frías-De-León María Guadalupe , Rodríguez-Cerdeira Carmen
Published: September 2021

Sporotrichosis is a subcutaneous endemic mycosis caused by species of the Sporothrix schenckii complex. The most common clinical form of the disease is lymphocutaneous, while the fixed cutaneous and disseminated cutaneous forms are rare. Moreover, it is more prevalent in immunocompetent individuals. In this study, we present two cases of sporotrichosis with uncommon clinical forms: fixed cutaneous (Case 1) and disseminated cutaneous (Case 2). Both cases were diagnosed in immunocompetent males from endemic regions in Mexico, who had at least 1 year of evolution without improvement in response to prior nonspecific treatments. The diagnosis of sporotrichosis caused by S. schenckii sensu stricto was established through the isolation of the pathogen and its identification through the amplification of a 331 bp fragment of the gene encoding calmodulin. In both cases, improvement was observed after treatment with potassium iodide. Cases 1 and 2 illustrate the rarity of these clinical forms in individuals residing in endemic areas; hence, it is important to ensure a high index of clinical suspicion for the diagnosis of mycosis, as the differential diagnoses vary widely.
Retinoids in Fungal Infections: From Bench to Bedside
Authors: Cosio Terenzio , Gaziano Roberta , Zuccari Guendalina , Costanza Gaetana , Grelli Sandro , Di Francesco Paolo , Bianchi Luca , Campione Elena
Published: September 2021

Retinoids—a class of chemical compounds derived from vitamin A or chemically related to it—are used especially in dermatology, oncohematology and infectious diseases. It has been shown that retinoids—from their first generation—exert a potent antimicrobial activity against a wide range of pathogens, including bacteria, fungi and viruses. In this review, we summarize current evidence on retinoids’ efficacy as antifungal agents. Studies were identified by searching electronic databases (MEDLINE, EMBASE, PubMed, Cochrane, Trials.gov) and reference lists of respective articles from 1946 to today. Only articles published in the English language were included. A total of thirty-nine articles were found according to the criteria. In this regard, to date, In vitro and In vivo studies have demonstrated the efficacy of retinoids against a broad-spectrum of human opportunistic fungal pathogens, including yeast fungi that normally colonize the skin and mucosal surfaces of humans such as Candida spp., Rhodotorula mucilaginosa and Malassezia furfur, as well as environmental moulds such as Aspergillus spp., Fonsecae monofora and many species of dermatophytes associated with fungal infections both in humans and animals. Notwithstanding a lack of double-blind clinical trials, the efficacy, tolerability and safety profile of retinoids have been demonstrated against localized and systemic fungal infections.
Computational Approach Reveals Pronociceptive Potential of Cannabidiol in Osteoarthritis: Role of Transient Receptor Potential Channels
Authors: Mlost Jakub , Kędziora Marta , Starowicz Katarzyna
Published: September 2021

Systems pharmacology employs computational and mathematical methods to study the network of interactions a drug may have within complex biological pathways. These tools are well suited for research on multitarget drugs, such as natural compounds, in diseases with complex etiologies, such as osteoarthritis (OA). The present study focuses on cannabidiol (CBD), a non-psychoactive constituent of cannabis, targeting over 60 distinct molecular targets as a potential treatment for OA, a degenerative joint disease leading to chronic pain with a neuropathic component. We successfully identified molecular targets of CBD that were relevant in the context of OA treatment with both beneficial and detrimental effects. Our findings were confirmed by in vivo and molecular studies. A key role of PPARγ in mediating the therapeutic potential of CBD was revealed, whereas upregulation of multiple transient receptor potential channels demasked CBD-induced heat hyperalgesia. Our findings pave the way for novel CBD-based therapy with improved therapeutic potential but also encourage the use of bioinformatic tools to predict the mechanism of action of CBD in different conditions. We have also created an accessible web tool for analogous analysis of CBD pharmacology in the context of any disease of interest and made it publicly available.
DAKS1, a Kunitz Scaffold Peptide from the Venom Gland of Deinagkistrodon acutus Prevents Carotid-Artery and Middle-Cerebral-Artery Thrombosis via Targeting Factor XIa
Authors: Jia Zhiping , Liu Yunyang , Ji Xiaoru , Zheng Yizheng , Li Zhengyang , Jiang Shuai , Li Hongjin , Kong Yi
Published: September 2021

Scaffold-based peptides (SBPs) are fragments of large proteins that are characterized by potent bioactivity, high thermostability, and low immunogenicity. Some SBPs have been approved by the FDA for human use. In the present study, we developed SBPs from the venom gland of Deinagkistrodon acutus (D. acutus) by combining transcriptome sequencing and Pfam annotation. To that end, 10 Kunitz peptides were discovered from the venom gland of D. acutus, and most of which peptides exhibited Factor XIa (FXIa) inhibitory activity. One of those, DAKS1, exhibiting strongest inhibitory activity against FXIa, was further evaluated for its anticoagulant and antithrombotic activity. DAKS1 prolonged twofold APTT at a concentration of 15 μM in vitro. DAKS1 potently inhibited thrombosis in a ferric chloride-induced carotid-artery injury model in mice at a dose of 1.3 mg/kg. Furthermore, DAKS1 prevented stroke in a transient middle cerebral-artery occlusion (tMCAO) model in mice at a dose of 2.6 mg/kg. Additionally, DAKS1 did not show significant bleeding risk at a dose of 6.5 mg/kg. Together, our results indicated that DAKS1 is a promising candidate for drug development for the treatment of thrombosis and stroke disorders.
Dose Response of Bumetanide on Aquaporins and Angiogenesis Biomarkers in Human Retinal Endothelial Cells Exposed to Intermittent Hypoxia
Authors: Guzel Sibel , Cai Charles L. , Aranda Jacob V. , Beharry Kay D.
Published: September 2021

Aquaporins (AQPs) are important for regulating cellular water, solute transport, and balance. Recently, AQPs have also been recognized as playing a key role in cell migration and angiogenesis. In the retina, hypoxia induces vascular endothelial growth factor (VEGF), a potent angiogenic and vascular permeability factor, resulting in retinal edema, which is facilitated by AQPs. Bumetanide is a diuretic agent and AQP 1–4 blocker. We tested the hypothesis that bumetanide suppression of AQPs ameliorates intermittent hypoxia (IH)-induced angiogenesis and oxidative stress in human microvascular retinal endothelial cells (HMRECs). HMRECs were treated with a low-dose (0.05 µg/mL) or high-dose (0.2 µg/mL) of bumetanide and were exposed to normoxia (Nx), hyperoxia (50% O2), or IH (50% O2 with brief hypoxia 5% O2) for 24, 48, and 72 h. Angiogenesis and oxidative stress biomarkers were determined in the culture media, and the cells were assessed for tube formation capacity and AQP-1 and -4 expression. Both doses of bumetanide significantly decreased oxidative stress and angiogenesis biomarkers. This response was reflected by reductions in tube formation capacity and AQP expression. These findings confirm the role of AQPs in retinal angiogenesis. Therapeutic targeting of AQPs with bumetanide may be advantageous for IH-induced aberrant retinal development.
NbX: Machine Learning-Guided Re-Ranking of Nanobody–Antigen Binding Poses
Authors: Tam Chunlai , Kumar Ashutosh , Zhang Kam Y. J.
Published: September 2021

Modeling the binding pose of an antibody is a prerequisite to structure-based affinity maturation and design. Without knowing a reliable binding pose, the subsequent structural simulation is largely futile. In this study, we have developed a method of machine learning-guided re-ranking of antigen binding poses of nanobodies, the single-domain antibody which has drawn much interest recently in antibody drug development. We performed a large-scale self-docking experiment of nanobody–antigen complexes. By training a decision tree classifier through mapping a feature set consisting of energy, contact and interface property descriptors to a measure of their docking quality of the refined poses, significant improvement in the median ranking of native-like nanobody poses by was achieved eightfold compared with ClusPro and an established deep 3D CNN classifier of native protein–protein interaction. We further interpreted our model by identifying features that showed relatively important contributions to the prediction performance. This study demonstrated a useful method in improving our current ability in pose prediction of nanobodies.
Posidonia oceanica (L.) Delile Extract Reduces Lipid Accumulation through Autophagy Activation in HepG2 Cells
Authors: Vasarri Marzia , Barletta Emanuela , Degl’Innocenti Donatella
Published: September 2021

Posidonia oceanica (L.) Delile is a marine plant traditionally used as an herbal medicine for various health disorders. P. oceanica leaf extract (POE) has been shown to be a phytocomplex with cell-safe bioactivities, including the ability to trigger autophagy. Autophagy is a key pathway to counteract non-alcoholic fatty liver disease (NAFLD) by controlling the breakdown of lipid droplets in the liver. The aim of this study was to explore the ability of POE to trigger autophagy and reduce lipid accumulation in human hepatoma (HepG2) cells and then verify the possible link between the effect of POE on lipid reduction and autophagy activation. Expression levels of autophagy markers were monitored by the Western blot technique in POE-treated HepG2 cells, whereas the extent of lipid accumulation in HepG2 cells was assessed by Oil red O staining. Chloroquine (CQ), an autophagy inhibitor, was used to study the relationship between POE-induced autophagy and intracellular lipid accumulation. POE was found to stimulate an autophagy flux over time in HepG2 cells by lowering the phosphorylation state of ribosomal protein S6, increasing Beclin-1 and LC3-II levels, and decreasing p62 levels. By blocking autophagy with CQ, the effect of POE on intracellular lipid accumulation was clearly reversed, suggesting that the POE phytocomplex may reduce lipid accumulation in HepG2 cells by activating the autophagic process. This work indicates that P. oceanica may be considered as a promising molecule supplier to discover new natural approaches for the management of NAFLD.
Anticancer Drug-Induced Cardiotoxicity: Insights and Pharmacogenetics
Authors: Adhikari Archana , Asdaq Syed Mohammed Basheeruddin , Al Hawaj Maitham A. , Chakraborty Manodeep , Thapa Gayatri , Bhuyan Nihar Ranjan , Imran Mohd. , Alshammari Mohammed Kanan , Alshehri Mohammed M. , Harshan Aishah Ali , Alanazi Abeer , Alhazmi Bushra Dhuhayyan , Sreeharsha Nagaraja
Published: September 2021

The advancement in therapy has provided a dramatic improvement in the rate of recovery among cancer patients. However, this improved survival is also associated with enhanced risks for cardiovascular manifestations, including hypertension, arrhythmias, and heart failure. The cardiotoxicity induced by chemotherapy is a life-threatening consequence that restricts the use of several chemotherapy drugs in clinical practice. This article addresses the prevalence of cardiotoxicity mediated by commonly used chemotherapeutic and immunotherapeutic agents. The role of susceptible genes and radiation therapy in the occurrence of cardiotoxicity is also reviewed. This review also emphasizes the protective role of antioxidants and future perspectives in anticancer drug-induced cardiotoxicities.