bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of Chemotherapy Regimens on Body Composition of Breast Cancer Women: A Multicenter Study across Four Brazilian Regions
Authors: Godinho-Mota Jordana Carolina Marques , Vaz-Gonçalves Larissa , Dias Custódio Isis Danyelle , Schroeder de Souza Jaqueline , Mota João Felipe , Gonzalez Maria Cristina , Rodrigues Vilella Priscylla , Anusca Martins Karine , Paiva Maia Yara Cristina de , Verde Sara Maria Moreira Lima , Frenzel Aline Porciúncula , Di Pietro Patricia Faria , Costa Marinho Eduarda da , Freitas-Junior Ruffo
Published: March 2023

This study aimed to investigate the effect of chemotherapy (CT) and its different types of regimens on the anthropometry and body composition of women with breast cancer. Three-hundred-and-four women with breast cancer were enrolled in this multicenter study. The participants were evaluated before the infusion of the first cycle of CT (pre-CT), and until two weeks after CT completion (post-CT), regarding body weight, body mass index (BMI); waist circumference (WC); waist-to-height ratio (WHtR); conicity index (C-index); fat mass index (FMI); and fat-free mass index (FFMI). CT regimens were classified as anthracycline-based (AC—doxorubicin or epirubicin); anthracyclines and taxane (ACT); cyclophosphamide, methotrexate, and 5-fluorouracil (CMF); or isolated taxanes (paclitaxel or docetaxel). Women significantly increased BMI and FMI post-CT (p < 0.001 and p = 0.007, respectively). The ACT regimen increased FMI (p < 0.001), while FFMI increased after AC (p = 0.007). It is concluded that the CT negatively impacted body composition and the type of regime had a strong influence. The ACT regimen promoted an increase in FMI compared to other regimens, and the AC increased FFMI. These findings reinforce the importance of nutritional monitoring of breast cancer patients throughout the entire CT treatment.
Where We Are and Where We Are Going in Nut Research
Authors: Salas-Salvadó Jordi , Nishi Stephanie K. , Sabaté Joan , Ros Emilio
Published: March 2023

Nuts have been part of the human diet for thousands of years [...]
Association between Genotype and the Glycemic Response to an Oral Glucose Tolerance Test: A Systematic Review
Authors: Bayer Sandra , Reik Anna , von Hesler Lena , Hauner Hans , Holzapfel Christina
Published: March 2023

The inter-individual variability of metabolic response to foods may be partly due to genetic variation. This systematic review aims to assess the associations between genetic variants and glucose response to an oral glucose tolerance test (OGTT). Three databases (PubMed, Web of Science, Embase) were searched for keywords in the field of genetics, OGTT, and metabolic response (PROSPERO: CRD42021231203). Inclusion criteria were available data on single nucleotide polymorphisms (SNPs) and glucose area under the curve (gAUC) in a healthy study cohort. In total, 33,219 records were identified, of which 139 reports met the inclusion criteria. This narrative synthesis focused on 49 reports describing gene loci for which several reports were available. An association between SNPs and the gAUC was described for 13 gene loci with 53 different SNPs. Three gene loci were mostly investigated: transcription factor 7 like 2 (TCF7L2), peroxisome proliferator-activated receptor gamma (PPARγ), and potassium inwardly rectifying channel subfamily J member 11 (KCNJ11). In most reports, the associations were not significant or single findings were not replicated. No robust evidence for an association between SNPs and gAUC after an OGTT in healthy persons was found across the identified studies. Future studies should investigate the effect of polygenic risk scores on postprandial glucose levels.
Prevalence of Relative Energy Deficiency in Sport (RED-S) among National Athletes in Malaysia
Authors: Marzuki Muhammad Irfan Haiqal , Mohamad Mohd Izham , Chai Wen Jin , Farah Nor M. F. , Safii Nik Shanita , Jasme Jasmiza Khuzairi , Jamil Nor Aini
Published: March 2023

Relative energy deficiency in sport (RED-S), which underpins the concept of low energy availability (LEA), can negatively affect athletes’ health and performance. This study aims to investigate the prevalence of RED-S among national athletes in Malaysia. A total of 192 national athletes (97 males, 18–39 years old) responded to an online survey regarding the RED-S risk. Most athletes (67.2%) were classified as having a medium/high RED-S risk. Female (41.2%), weight-class (23.9%), and intermittent sports (20.3%) had the highest prevalence of medium/high RED-S risk. Overall, most athletes spent 2–5 h daily (55.2%) and 6–7 days weekly (53.6%) practicing or playing their sport, and 47.9% reported feeling tired recently. The athletes were also terrified of being overweight (61.5%), worried about what they eat (64.7%), concerned about having fat on their bodies (62.6%), and thinking about burning calories while exercising (69.3%). Only 16.7% of the athletes had a prior history of stress fractures, and 40.6% continued to participate in activities 6–7 days per week while injured. The majority of female athletes (88.3%) had regular menstrual cycles. These findings support the notion that RED-S screening should be addressed in the athletic community. Future research is needed to clinically assess these athletes and investigate the impacts of RED-S on their health and sports performance.
Psychobiotic Effects on Anxiety Are Modulated by Lifestyle Behaviors: A Randomized Placebo-Controlled Trial on Healthy Adults
Authors: Morales-Torres Ricardo , Carrasco-Gubernatis Cristóbal , Grasso-Cladera Aitana , Cosmelli Diego , Parada Francisco J. , Palacios-García Ismael
Published: March 2023

Psychobiotics are modulators of the Microbiota-Gut-Brain Axis (MGBA) with promising benefits to mental health. Lifestyle behaviors are established modulators of both mental health and the MGBA. This randomized placebo-controlled clinical trial (NCT04823533) on healthy adults (N = 135) tested 4 weeks of probiotic supplementation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175). We assessed effects on wellbeing, quality of life, emotional regulation, anxiety, mindfulness and interoceptive awareness. We then analyzed if lifestyle behaviors modulated probiotic effectiveness. Results showed no significant effects of probiotic intake in whole sample outcomes. Correlational analyses revealed Healthy Behaviors were significantly correlated with wellbeing across scales. Moreover, the linear mixed-effects model showed that the interaction between high scores in Healthy Behaviors and probiotic intake was the single significant predictor of positive effects on anxiety, emotional regulation, and mindfulness in post-treatment outcomes. These findings highlight the relevance of controlling for lifestyle behaviors in psychobiotic and mental health research.
Mixed Berry Juice and Cellulose Fiber Have Differential Effects on Peripheral Blood Mononuclear Cell Respiration in Overweight Adults
Authors: Solverson Patrick , Albaugh George P. , Debelo Hawi A. , Ferruzzi Mario G. , Baer David J. , Novotny Janet A.
Published: March 2023

Berries and other anthocyanin-rich foods have demonstrated anti-obesity effects in rodents and humans. However, the bioactive components of these foods and their mechanisms of action are unclear. We conducted an intervention study with overweight and obese adults to isolate the effects of different berry components on bioenergetics. Subjects consumed whole mixed berries (high anthocyanin, high fiber), pressed berry juice (high anthocyanin, low fiber), berry-flavored gelatin (low anthocyanin, low fiber), or fiber-enriched gelatin (low anthocyanin, high fiber) for one week prior to a meal challenge with the same treatment food as the pre-feed period. Peripheral blood mononuclear cells were collected 2 h after the meal challenge, and cellular respiration was assessed via high-resolution respirometry. The high-anthocyanin, low-fiber treatment (berry juice) and the low-anthocyanin, high-fiber treatment (fiber-enriched gelatin) had opposite effects on cellular respiration. In the fasted state, berry juice resulted in the highest oxygen-consumption rate (OCR), while fiber-enriched gelatin resulted in the highest OCR in the fed state. Differences were observed in multiple respiration states (basal, state 3, state 4, uncoupled), with the greatest differences being between the pressed berry juice and the fiber-enriched gelatin. Different components of berries, specifically anthocyanins/flavonoids and fiber, appear to have differential effects on cellular respiration.
Magnesium in Kidney Function and Disease—Implications for Aging and Sex—A Narrative Review
Authors: Macías Ruiz María del Carmen , Cuenca Bermejo Lorena , Veronese Nicola , Fernández Villalba Emiliano , González Cuello Ana María , Kublickiene Karolina , Raparelli Valeria , Norris Colleen M. , Kautzky-Willer Alexandra , Pilote Louise , Barbagallo Mario , Dominguez Ligia , Herrero María Trinidad
Published: March 2023

Magnesium (Mg) has a vital role in the human body, and the kidney is a key organ in the metabolism and excretion of this cation. The objective of this work is to compile the available evidence regarding the role that Mg plays in health and disease, with a special focus on the elderly population with chronic kidney disease (CKD) and the eventual sex differences. A narrative review was carried out by executing an exhaustive search in the PubMed, Scopus, and Cochrane databases. Ten studies were found in which the role of Mg and sex was evaluated in elderly patients with CKD in the last 10 years (2012–2022). The progression of CKD leads to alterations in mineral metabolism, which worsen as the disease progresses. Mg can be used as a coadjuvant in the treatment of CKD patients to improve glomerular filtration, but its use in clinical applications needs to be further characterized. In conclusion, there’s a need for well-designed prospective clinical trials to advise and standardize Mg supplementation in daily clinical practice, taking age and sex into consideration.
Validation of a Phosphorus Food Frequency Questionnaire in Patients with Kidney Failure Undertaking Dialysis
Authors: Beer Joanne , Lambert Kelly , Lim Wai , Bettridge Ellen , Woodward Fiona , Boudville Neil
Published: March 2023

Nutritional guidelines recommended limiting dietary phosphorus as part of phosphorus management in patients with kidney failure. Currently, there is no validated phosphorus food frequency questionnaire (P-FFQ) to easily capture this nutrient intake. An FFQ of this type would facilitate efficient screening of dietary sources of phosphorus and assist in developing a patient-centered treatment plan. The objectives of this study were to develop and validate a P-FFQ by comparing it with the 24 hr multi-pass recall. Fifty participants (66% male, age 70 ± 13.3 years) with kidney failure undertaking dialysis were recruited from hospital nephrology outpatient departments. All participants completed the P-FFQ and 24 hr multi-pass recalls with assistance from a renal dietitian and then analysed using nutrient analysis software. Bland–Altman analyses were used to determine the agreement between P-FFQ and mean phosphorus intake from three 24 hr multi-pass recalls. Mean phosphorous intake was 1262 ± 400 mg as determined by the 24 hr multi pass recalls and 1220 ± 348 mg as determined by the P-FFQ. There was a moderate correlation between the P-FFQ and 24 hr multi pass recall (r = 0.62, p = 0.37) with a mean difference of 42 mg (95% limits of agreement: 685 mg; −601 mg, p = 0.373) between the two methods. The precision of the P-FFQ was 3.33%, indicating suitability as an alternative to the 24 hr multi pass recall technique. These findings indicate that the P-FFQ is a valid, accurate, and precise tool for assessing sources of dietary phosphorus in people with kidney failure undertaking dialysis and could be used as a tool to help identify potentially problematic areas of dietary intake in those who may have a high serum phosphate.
Reduction of Plasma BCAAs following Roux-en-Y Gastric Bypass Surgery Is Primarily Mediated by FGF21
Authors: Shah Harsh , Kramer Alyssa , Mullins Caitlyn A. , Mattern Marie , Gannaban Ritchel B. , Townsend R. Leigh , Campagna Shawn R. , Morrison Christopher D. , Berthoud Hans-Rudolf , Shin Andrew C.
Published: March 2023

Type 2 diabetes (T2D) is a challenging health concern worldwide. A lifestyle intervention to treat T2D is difficult to adhere, and the effectiveness of approved medications such as metformin, thiazolidinediones (TZDs), and sulfonylureas are suboptimal. On the other hand, bariatric procedures such as Roux-en-Y gastric bypass (RYGB) are being recognized for their remarkable ability to achieve diabetes remission, although the underlying mechanism is not clear. Recent evidence points to branched-chain amino acids (BCAAs) as a potential contributor to glucose impairment and insulin resistance. RYGB has been shown to effectively lower plasma BCAAs in insulin-resistant or T2D patients that may help improve glycemic control, but the underlying mechanism for BCAA reduction is not understood. Hence, we attempted to explore the mechanism by which RYGB reduces BCAAs. To this end, we randomized diet-induced obese (DIO) mice into three groups that underwent either sham or RYGB surgery or food restriction to match the weight of RYGB mice. We also included regular chow-diet-fed healthy mice as an additional control group. Here, we show that compared to sham surgery, RYGB in DIO mice markedly lowered serum BCAAs most likely by rescuing BCAA breakdown in both liver and white adipose tissues. Importantly, the restored BCAA metabolism following RYGB was independent of caloric intake. Fasting insulin and HOMA-IR were decreased as expected, and serum valine was strongly associated with insulin resistance. While gut hormones such as glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) are postulated to mediate various surgery-induced metabolic benefits, mice lacking these hormonal signals (GLP-1R/Y2R double KO) were still able to effectively lower plasma BCAAs and improve glucose tolerance, similar to mice with intact GLP-1 and PYY signaling. On the other hand, mice deficient in fibroblast growth factor 21 (FGF21), another candidate hormone implicated in enhanced glucoregulatory action following RYGB, failed to decrease plasma BCAAs and normalize hepatic BCAA degradation following surgery. This is the first study using an animal model to successfully recapitulate the RYGB-led reduction of circulating BCAAs observed in humans. Our findings unmasked a critical role of FGF21 in mediating the rescue of BCAA metabolism following surgery. It would be interesting to explore the possibility of whether RYGB-induced improvement in glucose homeostasis is partly through decreased BCAAs.
Photoprotective Effect of Fermented and Aged Mountain-Cultivated Ginseng Sprout (Panax ginseng) on Ultraviolet Radiation-Induced Skin Aging in a Hairless Mouse Model
Authors: Lee Hee Yul , Kim Eun-Jin , Cho Du Yong , Jung Jea Gack , Kim Min Ju , Lee Jin Hwan , Kim Wanil , Kang Sang Soo , Cho Kye Man , Kang Dawon
Published: March 2023

Interest in foods that promote inner beauty increases with increases in exposure to ultraviolet (UV) rays and with improvements in quality of life. This study was performed to evaluate the efficacy of fermented and aged mountain-cultivated ginseng sprouts (FAMCGSs), which have higher anti-inflammatory and antioxidant effects compared to mountain-cultivated ginseng sprouts (MCGSs), as an inner beauty enhancing food. The effect of orally administered FAMCGSs on UV type B (UVB) radiation-induced skin aging was investigated in a hairless mouse model through analyzing skin parameters including epidermal thickness, transepidermal water loss (TEWL), roughness, moisture, elasticity, and collagen contents. The mice exposed to UVB had markedly greater epidermal thickness, TEWL, and skin roughness than those of the normal control (NC) group. In addition, the levels of collagen, skin moisture, and dermal elasticity were lower in the UVB radiation group than the NC group. These UVB-induced skin aging parameters were significantly lower in the groups administered FAMCGSs than in the groups not administered FAMCGSs (p < 0.05). These results show that FAMCGSs exhibit a photoprotective effect in mice exposed to UVB and suggest that FAMCGSs can be used as a food that promotes inner beauty and protects skin from UVB-induced photoaging.
The Preventive Effect of Exercise and Oral Branched-Chain Amino Acid Supplementation on Obesity-Induced Brain Changes in Ldlr−/−.Leiden Mice
Authors: Lohkamp Klara J. , van den Hoek Anita M. , Solé-Guardia Gemma , Lisovets Maria , Alves Hoffmann Talissa , Velanaki Konstantina , Geenen Bram , Verweij Vivienne , Morrison Martine C. , Kleemann Robert , Wiesmann Maximilian , Kiliaan Amanda J.
Published: March 2023

Exercise and dietary interventions are promising approaches to tackle obesity and its obesogenic effects on the brain. We investigated the impact of exercise and possible synergistic effects of exercise and branched-chain amino acids (BCAA) supplementation on the brain and behavior in high-fat-diet (HFD)-induced obese Ldlr−/−.Leiden mice. Baseline measurements were performed in chow-fed Ldlr−/−.Leiden mice to assess metabolic risk factors, cognition, and brain structure using magnetic resonance imaging. Thereafter, a subgroup was sacrificed, serving as a healthy reference. The remaining mice were fed an HFD and divided into three groups: (i) no exercise, (ii) exercise, or (iii) exercise and dietary BCAA. Mice were followed for 6 months and aforementioned tests were repeated. We found that exercise alone changed cerebral blood flow, attenuated white matter loss, and reduced neuroinflammation compared to non-exercising HFD-fed mice. Contrarily, no favorable effects of exercise on the brain were found in combination with BCAA, and neuroinflammation was increased. However, cognition was slightly improved in exercising mice on BCAA. Moreover, BCAA and exercise increased the percentage of epididymal white adipose tissue and muscle weight, decreased body weight and fasting insulin levels, improved the circadian rhythm, and transiently improved grip strength. In conclusion, BCAA should be supplemented with caution, although beneficial effects on metabolism, behavior, and cognition were observed.
A Risk Profile for Disordered Eating Behaviors in Adolescents with Type 1 Diabetes: A Latent Class Analysis Study
Authors: Boccolini Giada , Marino Monica , Tiberi Valentina , Iannilli Antonio , Landi Giulia , Grandi Silvana , Tossani Eliana ,   ISPED Study Group, Cherubini Valentino
Published: March 2023

(1) Background: This multi-center study aimed to identify a risk profile for disordered eating behaviors (DEBs) in youth with type 1 diabetes (T1D) based on their dietary intake, lipid profile, body mass index (BMI-SDS), and glycometabolic control. (2) Methods: Adolescents aged 11 to 18 years from five centers across Italy were recruited. Lipid profile, HbA1c, BMI-SDS, and dietary intake data were collected. The risk for developing DEBs was assessed via the Diabetes Eating Problems Survey-R (DEPS-R) questionnaire. A latent class analysis (LCA) was performed using a person-centered approach. (3) Results: Overall, 148 participants aged 11–18 (12.1, ±3.34), 52% males with a mean diabetes duration of 7.2 (±3.4), were enrolled. Based on the results of the DEBS-R score, LCA allowed us to highlight two different classes of patients which were defined as “at-risk” and “not at-risk” for DEB. The risk profile for developing DEBs is characterized by higher BMI—SDS (23.9 vs. 18.6), higher HbA1c (7.9 vs. 7.1%), higher LDL cholesterol (99.9 vs. 88.8 mg/dL), lower HDL cholesterol (57.9 vs. 61.3 mg/dL), higher proteins (18.2 vs. 16.1%), and lower carbohydrates (43.9 vs. 45.3%). Adolescents included in the “at-risk” class were significantly older (p = 0.000), and their parents’ SES was significantly lower (p = 0.041). (4) Conclusions: This study allowed us to characterize a risk profile for DEBs based on dietary behavior and clinical parameters. Early identification of the risk for DEBs allows timely intervention and prevention of behavior disorders.
The Crosstalk between Gut Microbiota and White Adipose Tissue Mitochondria in Obesity
Authors: Colangeli Luca , Escobar Marcillo David Israel , Simonelli Valeria , Iorio Egidio , Rinaldi Tommaso , Sbraccia Paolo , Fortini Paola , Guglielmi Valeria
Published: March 2023

Adipose tissue (AT) dysregulation is a key process in the pathophysiology of obesity and its cardiometabolic complications, but even if a growing body of evidence has been collected over recent decades, the underlying molecular basis of adiposopathy remains to be fully understood. In this context, mitochondria, the intracellular organelles that orchestrate energy production and undergo highly dynamic adaptive changes in response to changing environments, have emerged as crucial regulators of both white (WAT) and brown adipose tissue (BAT) metabolism and function. Given that the gut microbiota and its metabolites are able to regulate host metabolism, adipogenesis, WAT inflammation, and thermogenesis, we hypothesize that their frequently observed dysregulation in obesity could affect AT metabolism by exerting direct and indirect effects on AT mitochondria. By collecting and revising the current evidence on the connections between gut microbiota and AT mitochondria in obesity, we gained insights into the molecular biology of their hitherto largely unexplored crosstalk, tracing how gut microbiota may regulate AT mitochondrial function.
Metabolomics Analysis Reveals Molecular Signatures of Metabolic Complexity in Children with Hypercholesterolemia
Authors: Gu Pei-Shin , Su Kuan-Wen , Yeh Kuo-Wei , Huang Jing-Long , Lo Fu-Sung , Chiu Chih-Yung
Published: March 2023

Despite the importance of hypercholesterolemia in children, it is overlooked, and there are currently few metabolomics-based approaches available to understand its molecular mechanisms. Children from a birth cohort had their cholesterol levels measured with the aim of identifying the metabolites for the molecular biological pathways of childhood hypercholesterolemia. One hundred and twenty-five children were enrolled and stratified into three groups according to cholesterol levels (acceptable, <170 mg/dL, n = 42; borderline, 170–200 mg/dL, n = 52; and high, >200 mg/dL, n = 31). Plasma metabolomic profiles were obtained by using 1H-nuclear magnetic resonance (NMR) spectroscopy, and partial least squares-discriminant analysis (PLS-DA) was applied using the MetaboAnalyst 5.0 platform. Metabolites significantly associated with different cholesterol statuses were identified, and random forest classifier models were used to rank the importance of these metabolites. Their associations with serum lipid profile and functional metabolic pathways related to hypercholesterolemia were also assessed. Cholesterol level was significantly positively correlated with LDL-C and Apo-B level, as well as HDL-C and Apo-A1 level separately, whereas HDL-C was negatively correlated with triglyceride level (p < 0.01). Eight metabolites including tyrosine, glutamic acid, ornithine, lysine, alanine, creatinine, oxoglutaric acid, and creatine were significantly associated with the different statuses of cholesterol level. Among them, glutamic acid and tyrosine had the highest importance for different cholesterol statuses using random forest regression models. Carbohydrate and amino acid metabolisms were significantly associated with different cholesterol statuses, with glutamic acid being involved in all amino acid metabolic pathways (FDR-adjusted p < 0.01). Hypercholesterolemia is a significant health concern among children, with up to 25% having high cholesterol levels. Glutamic acid and tyrosine are crucial amino acids in lipid metabolism, with glutamic-acid-related amino acid metabolism playing a significant role in regulating cholesterol levels.
The Role of Women’s and Men’s Body Shapes in Explicit and Implicit Fat Stigma
Authors: Krems Jaimie Arona , Bock Jarrod E.
Published: March 2023

Beyond being painful, fat stigma might facilitate pernicious consequences; over and above one’s weight, fat stigma is associated with lesser wellbeing, poorer health, greater all-cause mortality, and weight gains that perpetuate the weight-stigma cycle. To combat fat stigma effectively requires an understanding of the perceptual calculus underlying it. Here, we seized upon new work asserting that importance of a previously overlooked variable in this calculus—fat deposition location (body shape)—and we examine basic but fundamental open questions about the role of body shape in fat stigma via two experiments (one pre-registered). We replicate and extend work investigating how body shape—over and above body size—drives stigma toward women, using a figure set created specifically to test predictions about the role of body shape as well as size. We asked: (1) Are findings of greater explicit stigma toward adult women with abdominal (gut) versus gluteofemoral fat depositions (hips, thighs, buttocks) replicated—and (2) does this same finding hold for implicit stigma?; (3) Are male targets similarly stigmatized as a function of shape? (4) Do individual difference factors known to predict anti-fat stigma, e.g., Protestant Work Ethic, play a role here? We examined these questions by presenting American participants with women and men targets varying in both body size and shape—assessing participants’ explicit stigma (via self-report) and implicit stigma (via the Attitude Misattribution Procedure; AMP). We replicated the pattern that explicit fat stigma toward women is shape-sensitive and extend that to implicit stigma—finding, for example, that, of two women with the same exact heights and higher weights, the woman with abdominal fat deposition is more stigmatized than the woman with gluteofemoral fat deposition. We found no consistent results regarding the role of body shape in driving fat stigma toward men. We also found that some individual difference factors predicting anti-fat stigma were also attuned to body shape as well as body size. The results underscore the importance of integrating body shape into future work on fat stigma (toward women).
The Brown Alga Bifurcaria bifurcata Presents an Anthelmintic Activity on All Developmental Stages of the Parasitic Nematode Heligmosomoides polygyrus bakeri
Authors: Miclon Morgane , Courtot Élise , Guégnard Fabrice , Lenhof Océane , Boudesocque-Delaye Leslie , Matard-Mann Maria , Nyvall Collén Pi , Castagnone-Sereno Philippe , Neveu Cédric
Published: March 2023

The current control of gastrointestinal (GI) parasitic nematodes mainly relies on the widespread use of anthelmintics, which has inevitably led to resistance. Therefore, there is an urgent need to find new sources of antiparasitic compounds. Macroalgae represent a rich source of active molecules and are widely described as having medicinal properties. In the present study, we investigated the potential anthelmintic activity of aqueous extracts from three species of algae (Bifurcaria bifurcata, Grateloupia turuturu and Osmundea pinnatifida) on the murine parasite Heligmosomoides polygyrus bakeri. Using a set of complementary in vitro tests, including larval development assays, egg hatching tests and nematicidal activity assays on larvae and adults, we report the nematicidal activity of aqueous extracts of B. bifurcata. In addition, aqueous extract fractionation using liquid/liquid partitioning with a solvent of increasing polarity was performed in order to identify the groups of active molecules underlying the anthelmintic activity. Non-polar extracts (heptane, ethyl acetate) demonstrated high anthelmintic potential, highlighting the role of non-polar metabolites such as terpenes. Here, we highlight the strong anthelmintic potential of the brown alga B. bifurcata on a mouse model of GI parasites, thus confirming the strong interest in algae as natural alternatives for the control of parasitic nematodes.
Hydrodynamic Delivery: Characteristics, Applications, and Technological Advances
Authors: Suda Takeshi , Yokoo Takeshi , Kanefuji Tsutomu , Kamimura Kenya , Zhang Guisheng , Liu Dexi
Published: March 2023

The principle of hydrodynamic delivery was initially used to develop a method for the delivery of plasmids into mouse hepatocytes through tail vein injection and has been expanded for use in the delivery of various biologically active materials to cells in various organs in a variety of animal species through systemic or local injection, resulting in significant advances in new applications and technological development. The development of regional hydrodynamic delivery directly supports successful gene delivery in large animals, including humans. This review summarizes the fundamentals of hydrodynamic delivery and the progress that has been made in its application. Recent progress in this field offers tantalizing prospects for the development of a new generation of technologies for broader application of hydrodynamic delivery.
Platelet Activation by Antisense Oligonucleotides (ASOs) in the Göttingen Minipig, including an Evaluation of Glycoprotein VI (GPVI) and Platelet Factor 4 (PF4) Ontogeny
Authors: Valenzuela Allan , Ayuso Miriam , Buyssens Laura , Bars Chloé , Van Ginneken Chris , Tessier Yann , Van Cruchten Steven
Published: March 2023

Antisense oligonucleotide (ASO) is a therapeutic modality that enables selective modulation of undruggable protein targets. However, dose- and sequence-dependent platelet count reductions have been reported in nonclinical studies and clinical trials. The adult Göttingen minipig is an acknowledged nonclinical model for ASO safety testing, and the juvenile Göttingen minipig has been recently proposed for the safety testing of pediatric medicines. This study assessed the effects of various ASO sequences and modifications on Göttingen minipig platelets using in vitro platelet activation and aggregometry assays. The underlying mechanism was investigated further to characterize this animal model for ASO safety testing. In addition, the protein abundance of glycoprotein VI (GPVI) and platelet factor 4 (PF4) was investigated in the adult and juvenile minipigs. Our data on direct platelet activation and aggregation by ASOs in adult minipigs are remarkably comparable to human data. Additionally, PS ASOs bind to platelet collagen receptor GPVI and directly activate minipig platelets in vitro, mirroring the findings in human blood samples. This further corroborates the use of the Göttingen minipig for ASO safety testing. Moreover, the differential abundance of GPVI and PF4 in minipigs provides insight into the influence of ontogeny in potential ASO-induced thrombocytopenia in pediatric patients.
Designing Lignin-Based Biomaterials as Carriers of Bioactive Molecules
Authors: Abdullah Turdimuhammad , İlyasoğlu Gülmire , Memić Adnan
Published: March 2023

There is a need to develop circular and sustainable economies by utilizing sustainable, green, and renewable resources in high-tech industrial fields especially in the pharmaceutical industry. In the last decade, many derivatives of food and agricultural waste have gained considerable attention due to their abundance, renewability, biocompatibility, environmental amiability, and remarkable biological features. Particularly, lignin, which has been used as a low-grade burning fuel in the past, recently attracted a lot of attention for biomedical applications because of its antioxidant, anti-UV, and antimicrobial properties. Moreover, lignin has abundant phenolic, aliphatic hydroxyl groups, and other chemically reactive sites, making it a desirable biomaterial for drug delivery applications. In this review, we provide an overview of designing different forms of lignin-based biomaterials, including hydrogels, cryogels, electrospun scaffolds, and three-dimensional (3D) printed structures and how they have been used for bioactive compound delivery. We highlight various design criteria and parameters that influence the properties of each type of lignin-based biomaterial and corelate them to various drug delivery applications. In addition, we provide a critical analysis, including the advantages and challenges encountered by each biomaterial fabrication strategy. Finally, we highlight the prospects and future directions associated with the application of lignin-based biomaterials in the pharmaceutical field. We expect that this review will cover the most recent and important developments in this field and serve as a steppingstone for the next generation of pharmaceutical research.
Approaches to Assure Similarity between Pharmaceutical Heparins from Two Different Manufacturers
Authors: Bezerra Francisco Felipe , Oliveira Stephan N.M.C.G. , Sales Rodrigo A. , Piquet Adriana A. , Capillé Nina V. , Vilanova Eduardo , Tovar Ana M.F. , Mourão Paulo A.S.
Published: March 2023

Pharmaceutical heparins from different manufacturers may present heterogeneities due to particular extraction and purification procedures or even variations in the raw material manipulation. Heparins obtained from different tissues also differ in their structure and activity. Nevertheless, there is an increased demand for more accurate assessments to ensure the similarities of pharmaceutical heparins. We propose an approach to accurately assess the similarity of these pharmaceutical preparations based on well-defined criteria, which are verified with a variety of refined analytical methods. We evaluate six commercial batches from two different manufacturers which were formulated with Brazilian or Chinese active pharmaceutical ingredients. Biochemical and spectroscopic methods and analysis based on digestion with heparinases were employed to evaluate the purity and structure of the heparins. Specific assays were employed to evaluate the biological activity. We observed minor but significant differences between the constitutive units of the heparins from these two manufacturers, such as the content of N-acetylated α-glucosamine. They also have minor differences in their molecular masses. These physicochemical differences have no impact on the anticoagulant activity but can indicate particularities on their manufacturing processes. The protocol we propose here for analyzing the similarity of unfractionated heparins is analogous to those successfully employed to compare low-molecular-weight heparins.
Plasmonic Nanostructuring by Means of Industrial-Friendly Laser Techniques
Authors: Ntemogiannis Dimitrios , Floropoulos Panagiotis , Karoutsos Vagelis , Grammatikopoulos Spyridon , Poulopoulos Panagiotis , Alexandropoulos Dimitris
Published: March 2023

The continuously growing demand for functional plasmonic devices or systems urges the implementation of economical and accelerated nanostructuring techniques. Laser annealing represents a promising approach to address this challenge, given its widespread usage in industry and research, as well as its unique advantages. This study proposes a scalable, rapid, versatile, and cost-efficient method to grow self-assembled nanostructures on metallic ultrathin films and multilayers, with high precision and patterning freedom. By employing industrial-grade equipment, specifically a 1070 nm nanosecond fiber laser and magnetron sputtering system, we directly grew self-assembled nanoparticles on Ag ultrathin films and AgPd multilayers deposited on Corning glass, via laser annealing at ambient conditions. The self-assembled nanoparticles were formed in designated areas by varying several laser parameters and exhibited intense localized surface plasmon resonances. Optical and structural characterization were realized via UV–Vis spectroscopy and atomic force microscopy, respectively. The plasmonic characteristics were found to depend on the initial film thickness and laser annealing parameters. Laser-treated films exhibited remarkable plasmonic behavior, demonstrating that this method does not lack nanostructuring quality while offering scalability and practicality. Further optimization of the laser settings can refine the process and result in an even faster, cheaper, and more qualitative nanostructuring method.
Effects of Flavonoids and Phenols from Moringa oleifera Leaf Extracts on Biofilm Processes in Xanthomonas campestris pv. campestris
Authors: Fontana Riccardo , Caproni Anna , Sicurella Mariaconcetta , Manfredini Stefano , Baldisserotto Anna , Marconi Peggy
Published: March 2023

Xanthomonas campestris pv. campestris is the causal agent of black rot in crucifers, a plant disease with significant economic impact. Xanthomonadaceae is a large family of Gram-negative bacteria that cause symptoms by blocking water flow in plants by invading the xylem. To accomplish this, the main mechanism the bacteria use to adapt to environmental changes and colonize tissues is biofilm formation. In recent years, growing interest in natural antimicrobial compounds has led to the study of different phytocomplexes derived from plants. In this work, Moringa oleifera was selected, as its leaves are rich in phenols, essential oils, and vitamins that exert antibacterial activity. X. campestris pv. campestris biofilm, one of its major virulence factors, was studied. Biofilm formation and removal were analyzed on abiotic and biotic surfaces with and without M. oleifera leaf extracts. The data from the analysis show that Moringa oleifera leaf extracts and single phenols were able to inhibit biofilm growth on abiotic surfaces, but the activity of the whole phytocomplex was significantly higher compared to that of individual phenols. The effect of Moringa oleifera extracts on cabbage leaves in vivo was also found to be very important, as scanning electron microscopy showed that treatment with the extracts led to clear unblocking of the xylem, implying many advantages for use in black rot control.
Network Pharmacological Analysis and Experimental Validation of the Effect of Smilacis Glabrae Rhixoma on Gastrointestinal Motility Disorder
Authors: Choi Na-Ri , Lee Kangwook , Seo Mujin , Ko Seok-Jae , Choi Woo-Gyun , Kim Sang-Chan , Kim Jinsung , Park Jae-Woo , Kim Byung-Joo
Published: March 2023

Gastrointestinal motility disorder (GMD) is a disease that causes digestive problems due to inhibition of the movement of the gastrointestinal tract and is one of the diseases that reduce the quality of life of modern people. Smilacis Glabrae Rhixoma (SGR) is a traditional herbal medicine for many diseases and is sometimes prescribed to improve digestion. As a network pharmacological approach, we searched the TCMSP database for SGR, reviewed its constituents and target genes, and analyzed its relevance to gastrointestinal motility disorder. The effects of the SGR extract on the pacemaker activity in interstitial cells of Cajal (ICC) and gastric emptying were investigated. In addition, using the GMD mouse model through acetic acid (AA), we investigated the locomotor effect of SGR on the intestinal transit rate (ITR). As a result of network pharmacology analysis, 56 compounds out of 74 candidate compounds of SGR have targets, the number of targets is 390 targets, and there are 904 combinations. Seventeen compounds of SGR were related to GMD, and as a result of comparing the related genes with the GMD-related genes, 17 genes (active only) corresponded to both. When looking at the relationship network between GMD and SGR, it was confirmed that quercetin, resveratrol, SCN5A, TNF, and FOS were most closely related to GMD. In addition, the SGR extract regulated the pacemaker activity in ICC and recovered the delayed gastric emptying. As a result of feeding the SGR extract to AA-induced GMD mice, it was confirmed that the ITR decreased by AA was restored by the SGR extract. Through network pharmacology, it was confirmed that quercetin, resveratrol, SCN5A, TNF, and FOS were related to GMD in SGR, and these were closely related to intestinal motility. Based on these results, it is suggested that SGR in GMD restores digestion through the recovery of intestinal motility.
A Set of Molecular Markers to Accelerate Breeding and Determine Seed Purity of CMS Three-Line Hybrids in Brassica napus
Authors: Zhang Yanfeng , An Ran , Song Min , Xie Changgen , Wei Shihao , Wang Daojie , Dong Yuhong , Jia Qingli , Huang Shuhua , Mu Jianxin
Published: March 2023

Cytoplasmic male sterility (CMS) is the main mechanism employed to utilize the heterosis of Brassica napus. CMS three-line rapeseed hybrids have dramatically enhanced yield and brought about the global revolution of hybrid varieties, replacing conventional crop varieties. Over the last half century, China has led the development of hybrid Brassica napus varieties. Two sterile lines, polima (pol) and shaan 2A, were of particular importance for the establishment of three-line hybrid systems in rapeseed, which has opened up a new era of heterosis utilization. However, in current breeding practices, it takes up to three years to identify the restorer or maintainer relationship and the cytoplasmic type of any inbred material. This greatly affects the breeding speed of new varieties and inhibits the rapid development of the rapeseed industry. To address this problem, we developed a set of molecular markers for the identification of fertile cytoplasmic gene N and sterile cytoplasmic gene S, as well as for the fertile nucleus gene R and sterile nucleus gene r, based on differences in the gene sequences between the CMS line, maintainer line and restorer line of Brassica napus. Combining these markers can accurately identify the CMS line, maintainer and restorer of both the pol and shaan systems, as well as their hybrids. These markers can not only be used to identify of the maintainer and restorer relationship of inbred materials; they can also be used as general molecular markers to identify the CMS-type hybrid purity of pol and shaan systems.
Next-Generation Sequencing (NGS) Identified Species-Specific SSR and SNP Markers, Allow the Unequivocal Identification of Strawberry Tree (Arbutus unedo L.) Germplasm Accessions and Contribute to Assess Their Genetic Relationships
Authors: Pereira Ricardo , Anjos Isabela , Reis João , Dias Carolina , Leitão José
Published: March 2023

The strawberry tree (Arbutus unedo L.), an evergreen bush to small tree of the Ericaceae family, is a main component of the natural flora of the Mediterranean basin that also grows profusely through the Iberian Peninsula, southwestern France, and Ireland. The small edible red fruits are usually used to produce preserves, jams, and liquors, as the Portuguese “aguardente de medronho”. The leaves and fruits have been used for a long time in traditional medicine, and their bioactive compounds are presently the subject of intense research. A strawberry tree germplasm collection was recently established by the company Corte Velada (Odiáxere, Portugal). A set of 50 germplasm accessions was selected for a breeding program. A next-generation sequencing project was performed, resulting in the establishment of the first strawberry tree genome assembly and further identification of 500 SSR and 500 SNP loci. Individual molecular fingerprints for the unequivocal identification of the selected 50 accessions were established based on 71 markers alleles amplified by 4 SSR and 9 SNP markers. The same species-specific markers alleles combined with 61 random amplified markers amplified by 5 RAPD and 5 ISSR primers were used to assess the genetic variability and genetic relationships among the selected accessions.
Identification of the NAC Transcription Factor Family during Early Seed Development in Akebia trifoliata (Thunb.) Koidz
Authors: Liu Huijuan , Chen Songshu , Wu Xiaomao , Li Jinling , Xu Cunbin , Huang Mingjin , Wang Hualei , Liu Hongchang , Zhao Zhi
Published: March 2023

This study aimed to gain an understanding of the possible function of NACs by examining their physicochemical properties, structure, chromosomal location, and expression. Being a family of plant-specific transcription factors, NAC (petunia no apical meristem and Arabidopsis thaliana ATAF1, ATAF2, and CUC2) is involved in plant growth and development. None of the NAC genes has been reported in Akebia trifoliata (Thunb.) Koidz (A. trifoliata). In this study, we identified 101 NAC proteins (AktNACs) in the A. trifoliata genome by bioinformatic analysis. One hundred one AktNACs were classified into the following twelve categories based on the phylogenetic analysis of NAC protein: NAC-a, NAC-b, NAC-c, NAC-d, NAC-e, NAC-f, NAC-g, NAC-h, NAC-i, NAC-j, NAC-k, and NAC-l. The accuracy of the clustering results was demonstrated based on the gene structure and conserved motif analysis of AktNACs. In addition, we identified 44 pairs of duplication genes, confirming the importance of purifying selection in the evolution of AktNACs. The morphology and microstructure of early A. trifoliata seed development showed that it mainly underwent rapid cell division, seed enlargement, embryo formation and endosperm development. We constructed AktNACs co-expression network and metabolite correlation network based on transcriptomic and metabolomic data of A. trifoliata seeds. The results of the co-expression network showed that 25 AtNAC genes were co-expressed with 233 transcription factors. Metabolite correlation analysis showed that 23 AktNACs were highly correlated with 28 upregulated metabolites. Additionally, 25 AktNACs and 235 transcription factors formed co-expression networks with 141 metabolites, based on correlation analysis involving AktNACs, transcription factors, and metabolites. Notably, AktNAC095 participates in the synthesis of 35 distinct metabolites. Eight of these metabolites, strongly correlated with AktNAC095, were upregulated during early seed development. These studies may provide insight into the evolution, possible function, and expression of AktNACs genes.
Response of Maize (Zea mays L.) to Drought under Salinity and Boron Stress in the Atacama Desert
Authors: Riveros-Burgos Camilo , Bustos-Peña Richard , Esteban-Condori Wladimir , Bastías Elizabeth
Published: March 2023

The Lluta valley in northern Chile is a hyper-arid region with annual precipitation lower than 1.1 mm, and high levels of boron (B) from alluvial deposits are present together with other salts that originated from the Cretaceous. Under these abiotic conditions, the ‘lluteño’ maize (Zea mays L.) is of interest because it has adapted to the Lluta valley with high salinity levels and B excess in the soil and irrigation water. Water and salt stress coincide in heavily irrigated hyper-arid agricultural areas, yet they are usually studied in isolation. We investigated in field conditions the combined effects of drought (22 days with no irrigation) under salinity (ECe: 5.5 mS cm−1; Na+: 17.8 meq L−1) and B (21.1 meq L−1) stress on physiology, growth, yield, and hourly water relations. The results allow to hypothesize that the measurement of the pre-dawn water potential represents the balance between the water potential of the soil and the root. Besides, under drought a significant effect of irrigation and time interaction was observed presenting a high differential between the leaf and stem water potential in both phenological stages. Furthermore, a decrease in net assimilation was observed, and it could be explained in part by non-stomatal factors such as the high radiation and temperature observed at the end of the season. Despite the drought, the cobs did not present a significantly lower quality compared to the cobs of plants without stress.